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INFKCTini'S DISEASES 
 
 THEIR ETIOLOGY, DIAGNOSIS, AM) TREATMENT 
 
 BY 
 
 G. ii. j*<><; ee 
 
 PROFESSOR EXTRAORDINARY IN rilfr'u II.TV OF MKIilMSK OK PARI* 
 
 MEMBER OF THE BIOI.OUICAL SOCIETY 
 
 PHYSICIAN TO THE HOSPITAL OF POKTE I>' AT I'.l.l: \ I I.I II I:- 
 
 TRANSLATED BY 
 
 M. S. GABRIEL, M.I). 
 
 ILLUSTRATED WITH FORTY-THREE ENGRAVINGS 
 
 LEA BROTHERS & CO. 
 
 N E \Y Y R K AND PHIL A D E LPHI A 
 1903 
 
Enten-d according to the Act of Congress, in the year 1903, by 
 
 LEA BROTHERS & CO., 
 in the Office of the Librarian of Congress. All rights reserved. 
 
 I) O B N A N , PRINTKR. 
 
PREFACE. 
 
 Those members of the profession who confine their reading to 
 English alone will welcome this translation of Professor Roger'fi 
 great work. His subject comprehends almost the entire BCO] 
 internal medicine and touches many of the principles underlying 
 modern surgery as well. 
 
 During the last decades the marvellous discoveries in pathology 
 have succeeded one another with such bewildering rapidity that 
 time has apparently been lacking for the assimilation of the newly 
 acquired knowledge; and, as a result, many have failed to corre- 
 late the new theories with the old facts. The effect of the present 
 volume is to harmonize any seeming antagonism between experi- 
 mental research and clinical observation, and to reduce the theories 
 of infection and immunity to the basis of practical utility. 
 
 This material could not have been prepared by a laboratory 
 investigator however brilliant, nor by a clinician however pro- 
 found his experience, nor yet could it have been the product of 
 collaboration: its creation remained for one who combined the 
 instincts and training of a student at home in original research 
 with almost unprecedented opportunities for clinical investigation. 
 Possessed of an equal facility in each. Professor Roger has pursued 
 clinical and experimental researches jointly, although he always 
 subordinates the latter to the former and never loses sight of the 
 fact that the purpose of the laboratory is to amplify and explain 
 clinical observations, to the end that from both the therapist should 
 receive information indispensable to practical results. 
 
 With the directness of the true philosopher, the author unfolds 
 his subjects by using the simplest methods. He first studies the 
 
iv PREFACE. 
 
 pathogenic agents, inquires into their distribution in nature, the 
 
 conditions under which they attack man, and their mode of inva- 
 sion. Full consideration is then given to their influence upon 
 the human economy and the reaction of the latter upon the in- 
 vaders. Heredity, predisposition, and immunity receive specific 
 and general attention, while to the more directly practical depart- 
 ments of diagnosis, prognosis, and treatment, both preventive and 
 curative, ample time and space are devoted. 
 
 While the reading of no page may be omitted without loss, it 
 is desired to direct special attention to the author's consideration 
 of the influence of infection upon the various organs of the body 
 — his researches in experimental appendicitis, pseudotuberculosis, 
 variola, and the vesicatory test; also to his admirable treatment 
 of the pathology of fevers and the defenses of the organism against 
 infections. The final chapters, comprising more than a quarter 
 of the volume, are devoted to a masterly discussion of the thera- 
 peutics of infectious diseases. 
 
 As a basis for his opinions in the matter of treatment, as well 
 as the clinical observations reflected throughout the work, Pro- 
 fessor Roger has had recourse to the opportunities afforded him 
 at the Hotel Dieu and the isolation wards in the hospital of Porte 
 d'Aubervilliers. In these, the latter of which receives all cases 
 of contagious diseases occurring in Paris, he personally attended 
 over ten thousand patients during a period of five years. 
 
 The author knows his subject thoroughly, and, like a strong 
 man rejoicing in his strength, he takes a keen delight in grappling 
 with its problems. No doubt many readers will join him in this 
 pleasure and thereby become stronger men. 
 
(1 N T K N T S 
 
 CH A !' I E l: I . 
 General Considerations .17 
 
 CHAPTER II. 
 General Characters of Pathogenic Bacteria . . . 43 
 
 CHAPTER III. 
 Etiology of Infections ......... 
 
 CHAPTEE IV. 
 
 Pathogenesis of Infections ........ 
 
 CHAPTER V. 
 Microbic Associations . 135 
 
 CHAPTER VI. 
 
 Defenses and Reactions of the Organism ...... 
 
 CHAPTER VII. 
 Suppuration 
 
 CHAPTER VIII. 
 Gangrene . . . . . . . . . . . . .225 
 
 CHAPTER IX. 
 Septicemias and Pyemias . . . -44 
 
 CHAPTER X. 
 Nodular Infections . . . . . . . . . .272 
 
 CHAPTER XI 
 Cellular Degenerations ......... 323 
 
v j CONTENTS. 
 
 • 11 a PTER XII. 
 
 PAGF. 
 
 General Reactions -Fbveh 333 
 
 CHAPTER XIII. 
 Influence of 1mm riONS upon Various Parts of the Organism . 359 
 
 CHAPTER XIV. 
 Influence of Infection upon the Various Parts of the Organism 
 
 tinned) 402 
 
 CHAPTER XV. 
 Influence of Infection upon the Various Parts of the Organism 
 
 {Continued) 442 
 
 CHAPTER XVI. 
 Influence of Infection- cjpon the Various Parts of the Organism 
 
 (Concluded) 469 
 
 CHAPTER XVII. 
 Evolution of Infectious Diseases 494 
 
 CHAPTER XV III. 
 The Conseqi en< es of Infection 541 
 
 CHAPTER XIX. 
 Mechanism of Immunits and of Predisposition . . 551 
 
 CHAPTER XX. 
 Congenital Infection- and Heredity • 580 
 
 CHAPTER XXI. 
 Diagnosis and Prognosis of Infectious Diseases . . 606 
 
 CHAPTER XXII. 
 Therapeutics of Infectious Diseases ... ... 642 
 
 CHAP T E R XXIII. 
 Therapeutics of Infectious Diseases (Concluded) . ■ 757 
 
 CHAPTER XXIV. 
 Hygiene and Prophylaxis of Infectious Diseases . . ■ 837 
 
INFECTIOUS DISEASES. 
 
 CHAPTER I. 
 
 GENERAL CONSIDERATIONS. 
 
 Definition of Infectious Diseases. The Artificial Limits of thi- (iroup. Transition 
 between Infectious and Parasitic Diseases. Classification of infectious I' 
 Historical. Ancient Views of Infections. Analogy between Infections and 
 mentations. Researches upon the Animate Agents of Infections. The Patho- 
 genic Bacteria. Pathogenic Plants and Animals. Classification of Infectious 
 Agents. 
 
 Definition. The term "infection" is one of those words which are 
 most frequently employed in medicine and of which the meaning has 
 been most notably modified by time. While it was well defined by 
 the ancients, it is employed by modern authors without any attempt 
 to designate the precise meaning attributed to it at the present day. 
 
 To the ancients "infection'' meant everything that contaminates 
 the air. 1 From the time of Lucretius, Ovid, and Virgil until the days i if 
 Copland, the word was employed in this sense. The same idea was 
 expressed by Dupuytren, who believed that the cause of infection 
 resided in the action exerted upon the air by people crowded into 
 low, narrow, dark, and dirty localities, and by decaying vegetable 
 or animal substances. The air, when contaminated by such emana- 
 tions, becomes a true toxic agent. 
 
 It was only at a recent date that an attempt was made to differ- 
 entiate infection from contagion. 2 The two definitions proposed by 
 De la Berge, Monneret, and Fleury in their compendium 3 give a 
 clear idea of the conceptions prevailing in the first half of the nine- 
 teenth century. 
 
 1 Infection, from Latin infcctionan, infcctus. infect, or more exactly, impregnated: 
 in, jaccrc, to make in, to put in. 
 
 2 Contagion, contagio, from cum, tangerc, to touch. This term is applied to diseases 
 which originate by contact. 
 
 3 Compendium de med. pratique. 1S37. vol. ii. p. 463; vol. v. p. 167, 1S42. 
 
18 INFECTIOUS DISEASES. 
 
 "Infection."' they say, "is the mode of propagation of certain 
 diseases which depend upon the toxic or morbific action exerted by 
 decaying vegetable or animal substances and the miasms exhaled by 
 the healthy or diseased human body upon one or several individuals 
 placed under conditions which render them particularly susceptible 
 to their influence. 
 
 "Contagion is that mode of propagation of disease by which an 
 afflicted individual communicates the malady to others favorably 
 situated to receive it, and the latter, in their turn, become agents of 
 propagation of the disease the characters of which remain identical 
 throughout." 
 
 It is interesting to note that in the foregoing two definitions the 
 authors admit the necessity of morbid opportunity for the genesis 
 of infectious and contagious diseases — a conception that has been 
 fully confirmed by recent researches. On the other hand, the con- 
 tagious diseases which are always reproduced with the same char- 
 acters belong to what are at present designated as infectious diseases. 
 It is to be noted, however, that in passing from one individual to 
 another, the disease does not always preserve its primitive character. 
 Erysipelas, for instance, may engender puerperal fever. The defini- 
 tion of infections is still less successful, for it is applicable to a great 
 variety of morbid states due to intoxications. This confusion is 
 encountered even in recent works. Several processes that are in 
 reality to be attributed to autointoxication have been described 
 under the name of autoinfection. 
 
 It is thus evident that, toward the middle of the nineteenth cen- 
 tury, the diseases transmitted through the agency of air — i. e., mias- 
 matic diseases — were considered as infectious and were clearly dis- 
 tinguished from those conveyed by contact, either mediate or imme- 
 diate. 1 The limits of infections, however, were soon to be widened. 
 The miasmatic diseases were classed with those arising from inocu- 
 lation or absorption of decaying organic substances. The group of 
 autoinfections were thus created and included the two great processes 
 which are still designated as purulent and putrid infection. 
 
 We are thus brought to the present time, when investigators seeking 
 for the causes of these miasmatic diseases, putrid and purulent, 
 demonstrated the intervention of microscopic animate agents. These 
 animate agents were first discovered in the air, and the miasmatic 
 
 1 Chomel. El&nents de path. g<Sn<5rale, Paris, 1863, 5th ed., p. 38. 
 
GENERA L CONSIDER A TIONB. 1 !i 
 
 theory thus received experimental sanction. Next, thi fre- 
 
 quently seen lo vegetate upon our integumente and mucous mem- 
 branes, and the theory of autoinfection was established upon an 
 unassailable basis. 
 
 From that time infectious diseases were naturally considered to 
 be always dependent upon some animate agent. They constitute a 
 particular, autonomous group in the class of parasitic disea 
 
 Agreement upon this point is unanimous. Difficulty arises, how- 
 ever, when an attempt is made to learn the distinctive characters 
 separating infection from parasitism. The clinical symptom-, ol 
 course, are not comparable. No one would consider as infectious the 
 manifestations caused by taenia or the slight dermatitis excited by 
 miorosporon furfur. Nevertheless, considerable embarrassment is 
 experienced when accurate definitions are to be formulated. Hence, 
 most authors have avoided offering any, depending upon the ability 
 of the reader to comprehend what they were incapable of defining. 
 
 In view of these difficulties, some authors sought the character- 
 istics of infection in the agents generating the morbid manifestations, 
 and proposed to reserve the name infectious for diseases depending 
 upon the action of bacteria, To the author this view does not seem 
 acceptable. It is impossible to make etiological and pathogenic con- 
 ceptions the exclusive basis of a classification. The nosographer 
 must, first of all, weigh the various reactions of the organism, viz., 
 the symptoms presented by the patient: he must start from the 
 disturbances observed during life and proceed from the apparent 
 phenomena to the hidden cause. 
 
 The ancient physicians succeeded in individualizing typhoid fever, 
 anthrax, glanders, leprosy, and tuberculosis by the attentive study 
 of symptoms. Pathological anatomy completed the work begun by 
 clinicians. Modern researches in etiology have added little to ancient 
 conceptions and, in the majority of instances, have confirmed them. 
 Laennec's genius established the unity of tuberculosis merely through 
 the data furnished by clinical observation and macroscopic anatomy. 
 The histological researches of Grancher and Thaon confirmed Laen- 
 nec's conception. Koch's discovery, completing Yillemin's work, 
 furnished an unassailable basis for ancient ideas. It did no more 
 than permit the recognition of the tubercular character oi some less 
 clearly defined lesions of minor importance. 
 
 Clinical observation did not require the assistance of bacteriology 
 in describing the eruptive fevers. Nothing is better established than 
 
20 IXFECTIO US DISEASES. 
 
 this part of medicine. Mediate or immediate contagion, regular or 
 irregular types, malignant or benign, early or belated complications, 
 all had been observed by the older physicians, and it is hardly prob- 
 able that the discovery of the agents giving rise to these infections 
 will greatly modify the ancient descriptions. 
 
 Should bacteriological research be taken as an exclusive basis it 
 would lead to the separation of certain diseases which clinical obser- 
 vation seems to have rightly classed together. Paludism is the most 
 characteristic type of miasmatic infections. It is produced, not by 
 bacteria, but by animal parasites — protozoa. Accordingly, it should 
 be excluded from the group of infections, a step which no observer 
 would approve. The same is true also of smallpox, varicella, and 
 vaccinia, provided, as numerous investigations tend to prove, we 
 admit that they are due to animal parasites. Nevertheless, by their 
 symptomatic and contagious characters, they head the list of infec- 
 tious diseases. 
 
 The study of tuberculosis and actinomycosis furnishes fresh con- 
 firmation for our view. Clinical observers had noted strong analogies 
 between these two diseases. Bacteriology widened the breach sepa- 
 rating them. One of them, tuberculosis, was classed among the 
 infections, since it depends upon a bacillus ; the other, actinomycosis, 
 was included with parasitic diseases, as it is due to an algae whose 
 organization is far more complex. Recent researches, however, tend 
 to justify the clinical view by establishing a close relationship, at 
 first unsuspected, between the two pathogenic agents. The infective 
 agent of tuberculosis seems to have unduly occupied a place among 
 the bacilli. Under certain conditions this plant presents prolonga- 
 tions, ramifications, and swellings: it assumes the aspect of actino- 
 myces, and, like it, enters into the group of streptothrix or oospora. 
 Additional inquiry has thus established an etiological analogy cor- 
 responding to symptomatic analogy. If, however, bacterial diseases 
 alone should be considered as infectious, tuberculosis would have to 
 be excluded from the group of infections. If, on the other hand, 
 tuberculosis should be retained in that group, then actinomycosis 
 should also be assigned a like position; and there remains no reason 
 why those diseases which are caused by a certain species of asper- 
 gillus or certain yeasts should not be placed in the same category. 
 
 Abandoning etiological classification, some authors have chosen 
 pathogenesis as a basis. A disease should be called infectious or 
 parasitic, according to the mode of action of the cause. In the former 
 
< ; /<; N /<; ft A L co N8 WEBATIO ss. 2 1 
 
 case the morbific agenl acts by the soluble substances which it 
 secretes; in the latter instance its action is merely a mechanical one 
 
 — some form of I riiiiiii.-iiisin inflicted upon the tissues. 
 
 Such a conception is better. It would be perfect if we knew with 
 greater accuracy the mode of action of the pathogenic agents. At 
 any rate, this pathogenic classification docs not differ greatly from 
 symptomatic classifications, which I prefer, [f the reactions pre- 
 sented by diseased organisms arc of the same nature, the reason is 
 that the mode 1 of action of the agents calling them into play are 
 analogous. Classifications based upon pathogenesis are, however, 
 hardly possible as yet. Too much obscurity and discord still prevail 
 in this branch of medicine. It is, therefore, better to rely upon the 
 symptoms presented by the sick. This method is simpler and, it 
 seems to the writer, even more rational. For the philosopher as well 
 as for the practitioner, a classification must be founded upon observ- 
 able and not upon hidden signs. "We observe the morbid dis- 
 turbances, the clinical manifestations, and their study enables us to 
 discover the lesions which accompany them, the causes which pro- 
 duce them, and the mechanism which accounts for them. 
 
 What, then, are the clinical characters which will enable us to 
 recognize the infectious nature of a disease? 
 
 In many instances it is possible to ascertain the contagious nature 
 and epidemic progress of a disease; but this is not sufficient to prove 
 its infectious character. Certain nervous affections are contagious and 
 epidemic. The history of insanity and hysteria furnishes numerous 
 illustrations of this. The distinction is, as a rule, easy, though not 
 always. It was long believed that the contagiousness of whooping- 
 cough was due to nervous influence — some sort of imitation. To-day 
 it is known that there is actual transmission of a living germ. The 
 difficulty is as great with regard to intoxications. Poisoning is 
 at times epidemic or endemic, the affected individuals having ab- 
 sorbed nearly equal amounts of noxious substances. In infections, 
 particularly in those of aquatic origin, the study of etiological con- 
 ditions shows that the pathogenic agent was imponderable, and 
 that it must have increased by reproduction within the organism, 
 which fact demonstrates its animate nature. The surgical or puer- 
 peral septicemias transmitted through insufficiently cleansed instru- 
 ments or hands are of this nature. 
 
 In order that animate agents may develop and give rise to dis- 
 turbances, a certain length of time must elapse between their intro- 
 
22 INFECTIO US DISEASES. 
 
 duction into the system and the appearance of the first morbid 
 reactions. This is the period of incubation. It properly belongs to 
 infectious and parasitic diseases. In practice, however, it is often 
 impossible to distinguish the incubation period from the period of 
 latency observed under a great number of circumstances, notably 
 in intoxications and, at times, also in nervous reactions. 
 
 When the microbe is sufficiently developed the organism reacts 
 by two orders of manifestations, namely, local and general. The 
 local reactions cannot serve to characterize infection, for they appear 
 in many parasitic diseases, and also in various intoxications. The 
 general reactions, including fever, are likewise observed in poison- 
 ings, in autointoxications — gout, for example. 
 
 Thus, taken separately, each of the characters of infection presents 
 nothing special. We must, therefore, acknowledge the singular 
 genius of the early observers who, in the midst of analogous etio- 
 logical conditions and comparable symptomatic manifestations, 
 were able to classify the infectious processes. Modern researches 
 have in almost every instance confirmed the results of their intuition, 
 adding an element of certainty by the discovery of the animate 
 agent. 
 
 In our definition of infectious diseases we must, therefore, empha- 
 size the animate nature of the pathogenic agent. We will state that 
 infectious diseases belong to the class of parasitic diseases ; but they 
 here occupy a special place. How can we distinguish them? 
 
 Despite our endeavors, the distinction will necessarily be an arti- 
 ficial one. All attempts at classification are arbitrary, since distinc- 
 tions rest only upon differences of degree. However, let us attempt 
 to point out the limits between the two groups. 
 
 The fundamental character of the parasite is to live at the expense 
 of the being it inhabits without endangering the existence of its host.- 
 It exerts as little harmful influence upon the host as possible. If it 
 ever causes death it is as a matter of accident. Parasites, such as 
 intestinal worms and cutaneous parasites, do exert a toxic action, 
 but this is of a local character. The blue spots caused by the pedic- 
 ulis pubis express an intoxication which does not extend beyond 
 the integument. The pustules of scabies are produced by secondary 
 infections facilitated by the presence of the specific agent. At all 
 events, general reactions are absent, and if any do occur, they are of 
 a reflex nature, such as might be occasioned by any foreign body, 
 even of inorganic nature, that irritates the nerve terminations. Even 
 
GENERAL CONSIDERATIONS. 23 
 
 hydatid cyst is capable of exerting only mechanical action. If, al a 
 given moment, It gives rise to serious symptoms, \\ is -imply by 
 virtue of its excessive development, under which circumstance 
 
 compresses Hie adjacent organs. Ai. any rate, it does not .-i'- 1 other- 
 wise than would any oilier foreign body of the same -i/- 1. 
 It is to be noted, however, that all parasites contain and produce 
 
 toxic substances. It is a general law of biology that vital manifes- 
 tations result in the formation and excretion of noxious products. 
 On the other hand, a foreign body, whether of organic or inorganic 
 nature, provokes no reaction, either local or general, except through 
 the agency of the soluble substances which it diffuses. An abso- 
 lutely insoluble body excites no reaction whatever. While the 
 amount of dissolved matter is sufficient to influence the living cells 
 and particularly the nerve endings, it is at times too small to be 
 detected by our chemical reagents. Raulin's and Naegeli's experi- 
 ments in this connection are altogether conclusive. These reflection- 
 show the insignificant value of our classifications and demonstrate 
 that the various pathological processes are related to each other by 
 insensible transitions. 
 
 It may further be objected that certain living beings may. under 
 certain conditions, be considered parasites or infectious agents. Such, 
 for instance, is the case with oidium albicans, which is a simple 
 epiphyte in man and an infectious agent in animals. I think these 
 fungi should be classed with the infectious agents and not with the 
 true parasites, for they are capable of causing in animals a mycosis 
 analogous to bacterial diseases. Moreover, their subcutaneous inocu- 
 lation often gives rise to grave general manifestations, and may pro- 
 duce death in a few days. In man such an evolution is rare, but 
 we also find similar facts among bacteria. The pneumococcal strep- 
 tococcus, staphylococcus, and colon bacillus live upon our mucous 
 membranes as inoffensive parasites. They sometimes provoke small 
 superficial lesions of no greater importance than a patch of aphtha. 
 On other occasions the}'' rise to the rank of infectious agents and 
 cause violent reactions. 
 
 These few examples show how numerous are the transitions be- 
 tween infectious and parasitic diseases. Nevertheless. I believe it is 
 possible to distinguish the two groups of animate agents in the 
 following manner : 
 
 Parasitic agents exert a simple mechanical action upon the econ- 
 omy. The toxic substances produced by them are not sufficiently 
 
24 INFECTIO US DISEASES. 
 
 powerful to appreciably impress the whole organism. They give rise 
 only to some local phenomena. 
 
 The action of infectious agents upon the organism is complex. 
 Their mechanical role is very little, if at all, marked. They act 
 mainly through the noxious substances elaborated by them. For 
 this reason it is possible to say that infection, in the last analysis, 
 is intoxication of parasitic origin. 
 
 It will now be easier for us to understand how the group of infec- 
 tions should be formed. Inspired with the definition proposed by 
 Prof. Bouchard for disease in general, we shall say: Infectious diseases 
 are characterised by the phenomena manifested in an individual 
 wlien undergoing the action of parasitic toxins and reacting against 
 them. 
 
 Objections could be raised against this definition. It seems to the 
 writer, however, that it is quite in harmony with facts actually 
 known. It has the advantage of placing clinical phenomena in the 
 first rank, and at the same time it takes cognizance of etiology and 
 pathogenesis. If it is applicable to certain parasitic diseases, it is so 
 for the reason that facts constitute an uninterrupted chain in nature. 
 
 Classification of Infectious Diseases. 
 
 An exclusively microbiological classification is impossible, since 
 apparently identical clinical manifestations may be caused by differ- 
 ent microbes, and, on the other hand, one and the same microbe may 
 give rise to quite different manifestations. 
 
 These facts are well known. Suppuration, for instance, may be 
 engendered by the most diverse bacteria. Likewise, in intoxications, 
 many poisons produce the same symptoms: convulsions, paralyses, 
 coma. To recall a simpler illustration, excitation of a nerve, what- 
 ever the irritant employed, whether physical, chemical, or physio- 
 logical, always produces the same effect. The organism has at its 
 disposition but a limited number of responsive modes; hence it is 
 conceivable that, in pathology as well as in physiology, different 
 excitations may be followed by similar reactions. 
 
 To return to the microbes. Bacteriological researches have demon- 
 strated that ulcerative endocarditis may be the result of the action 
 of the most varied microbes. The same is true in regard to broncho- 
 pneumonias, and the anatomicoclinical distinctions which some 
 authors have attempted to establish according to the nature of the 
 
( ; /<; A' E RAL CONSIDERATIO ss. 2 6 
 
 pathogenic agent have been proved untenable by further researches 
 On the other hand, the same microbe is capable of exciting markedly 
 dissimilar manifestations. The streptococcus, for instance, produces 
 phlegmon, erysipelas, septicemias, pyemias, bronchopneumonias, 
 ulcerative endocarditis, etc. The same is true of the staphylococcus, 
 pneumococcus, and colon bacillus, which are mel with in a great 
 variety of lesions. 
 
 In view of these facts, some authors attempted to attack the 
 modern theories of pathogenesis and to minimize the importance 
 attributed to microbic agents. It must be acknowledged thai at 
 first the results seemed somewhat deceiving; but a comparative 
 study of the events occurring in infections and in intoxications will 
 show that the same dilliculty exists in both. 
 
 Any given poison may exert wholly different effects. Alcohol, for 
 instance, may cause drunkenness, delirium tremens, pachymenin- 
 gitis, pseudotabes, hepatic cirrhosis, etc. The same is true of other 
 poisons, such as phosphorus, arsenic, lead, and mercury. On the other 
 hand, apparently identical phenomena may be due to the action of 
 different poisons or occur even without the agency of any intoxication. 
 
 The results are, therefore, comparable in the various morbid groups, 
 and their study clearly demonstrates the impossibility of purely 
 etiological classifications. The inconstancy of results does not, how- 
 ever, constitute an exception to determinism, which is the basis of 
 all science. If the manifestations are dissimilar while the cause i- 
 the same, this is due simply to the fact that the action of the c 
 is exercised under different conditions. We must remember that no 
 two individuals are alike. Heredity and innateness impose upon each 
 person a particularism which becomes more marked as years pass 
 and the organism is subjected to numerous external influences. Since 
 individuals are different, reactions cannot be identical. The facts 
 observed by the physician are not, therefore, results of accident, but 
 thejr are so complicated and so varied that it is impossible to unite 
 them in a simple formula. 
 
 These reservations should not prevent the nosologist from taking 
 cognizance of etiological data which, though always interesting, have 
 acquired additional importance since the discovery of specific serums. 
 Bacteriological subdivisions should, therefore, be introduced into 
 clinical groupings. 
 
 Specific and Non-specific Infections. In the first place, infections 
 may be divided into two large classes, specific and non-specific. 
 
26 INFECTIOUS DISEASES. 
 
 Iii specific infections the pathogenic agent suffices to characterize 
 the disease. Such, for instance, are anthrax, tuberculosis, and diph- 
 theria. This class is divisible into three orders according as the 
 pathogenic parasite is a bacterium, a more highly organized plant, 
 or an animal agent. A fourth order, which will sooner or later dis- 
 appear, comprises those infections, such as hydrophobia, syphilis, 
 typhus fever, and scarlatina, the pathogenic agents of which have 
 not yet been discovered. 
 
 Non-specific infections differ from the preceding by the following 
 characters : 1 . They are due to common bacteria almost constantly 
 inhabiting our mucous membranes and skin, vegetating as simple 
 saprophytes. 2. Each clinical type may be produced by different 
 agents. 3. Each microbe may give rise to the most varied manifes- 
 tations. 
 
 Non-specific infections comprise exudative inflammations, such as 
 erysipelas; suppurative processes, such as phlegmon; degenerative 
 conditions, such as grave icterus ; pseudomembranous inflammations, 
 such as certain non-diphtheritic sore throats; ulcerating affections, 
 such as infectious endocarditis, and necrosing processes, such as pul- 
 monary gangrene. Now, the feature of dominant importance in the 
 history of these diseases is not the nature of the pathogenic agent, 
 but the morbid localization. The same microbe, staphylococcus 
 aureus, for example, produces furuncle, osteomyelitis, and ulcerative 
 endocarditis, yet no one would think of including in one chapter 
 affections so different from each other. These non-specific infections 
 must, therefore, be considered in connection with the organs in which 
 the process is localized, and with other ulcerations which may affect 
 the same viscera. 
 
 Subdivisions of Specific Infections. We will admit two groups in the 
 class of specific infections, placing general infections of septicemic 
 or pyemic character in the first group, and in the second those in 
 which visceral localization immediately attracts the clinician's atten- 
 tion as a matter of prime importance. 
 
 The general specific infections comprise three classes: eruptive 
 infections, septicemic infections, and infections with nodular pro- 
 ductions. 
 
 Eruptive injections possess an indisputable autonomy. They 
 cannot be ranked among infections with cutaneous determination. 
 They are general diseases, veritable septicemias, ushered in with 
 symptoms expressing an impregnation of the whole organism. Sub- 
 
GENERAL CONSIDERATIONS. il 
 
 sequently a sort of discharge toward the mucous membrane* and Hi'- 
 skin takes place, relieving the principal symptoms. The discharge 
 may be characterized by erythema, as in measl 
 rubeola, and sudor anglicusj by vesicles, as in zona; by bulls, ac 
 in varicella and polymorphous erythema; by vesicopustuies, ae in 
 vaccinia and smallpox. I lere belongs syphilis. "Venereal dia 
 is a denomination which should become! obsolete or be preserved only 
 for convenience. Otherwise, it- is wrong to form a group of di i 
 which have no relationship to each other excepl the fact that in the 
 majority of cases they are contracted through sexual intercourse, 
 though this etiological circumstance is not indispensable. Syphilis 
 begins as a local lesion, followed by a general impregnation of the 
 economy. Later on a discharge takes place toward the integuments. 
 This evolution, although slower, is identical with that of smallpox. 
 The comparison is altogether perfect if we select inoculated smallpox : 
 in this case there is a local lesion followed by general impregnation 
 and secondary eruption. The only difference resides in the fact 
 that syphilis runs a much slower course and, therefore, the reactions 
 are less intense. It is well, however, to remark that the comparison 
 is exact only during the first periods of the disease. After a certain 
 lapse of time syphilis gives rise to lesions which render it quite unlike 
 eruptive fevers. At this stage, however, the virus is profoundly 
 modified. Its contagiousness is nil or so slight that contamination 
 by tertiary accidents was long denied, and very few cases are quoted 
 even at the present day. This leads to the belief that syphilis is due 
 to a parasite which undergoes a long course of evolution within the 
 infected organism. After having provoked a highly contagious 
 exanthematic septicemia, it becomes localized at certain points and 
 produces local and non-transmissible lesions of a quite different 
 nature. 
 
 The second group comprises the infection* with septicemic tendency 
 exclusive of eruptive fevers. The author classes in this group typhoid 
 fever, typhus, influenza, bubonic plague, and anthrax. Typhoid 
 fever might be placed among infections of an intestinal determina- 
 tion, but the digestive disturbances, important as they are, do not 
 represent the principal symptom of the malady. The general reac- 
 tions expressing the impregnation of the whole organism are oi 
 greater importance. The same remark is applicable to bubonic 
 plague, the danger from which likewise results from the invasion of 
 the organism by the specific bacillus. The same is true of anthrax: 
 
28 IXFECTIO US DISEASES. 
 
 it is not the local lesion that kills; on the contrary, the prognosis 
 depends upon the resistance of the organism to general infection. 
 
 The infections with nodular productions seem to me to constitute 
 a group so natural as to require no further discussion. Glanders links 
 this group with septicopyemic infections. Tuberculosis, leprosy, 
 and nodular mycoses are characterized by entirely comparable reac- 
 tionary manifestations. 
 
 Non-specific infections are classified according to the predominat- 
 ing symptoms. In the majority of cases these symptoms are ex- 
 plained by the localization of the parasite. Tetanus alone is to be 
 excepted. The author has placed this disease among the infections 
 with nervous localization. Of course, the pathogenic agent remains 
 localized at some point of the economy, most frequently in the 
 cellular tissue, at times in some organ, and does not reach the nerve 
 centres at all, thus behaving otherwise than the parasite of hydro- 
 phobia. The nervous manifestations are, however, so predominant 
 that the clinician hesitates to assign to tetanus some other position 
 in nosology. At all events, the author's view is in accordance with 
 his definition of infectious diseases, since their characteristics must 
 be sought in the reaction of the organism to the action of microbic 
 toxin. The localization of the latter should guide the nosologist. 
 
 The writer has advisedly closely allied recurrent fever and palu- 
 dism. These two diseases seem to form a very natural group in the 
 classification. Their agents localize themselves in the organs con- 
 nected with the blood system, notably in the spleen, and, at a certain 
 moment, invade the blood itself. 
 
 As to the other infections, classification was easier. It was quite 
 natural to place dysentery and cholera among infections with intes- 
 tinal determination; yellow fever among infections with hepatic 
 determination, etc. 
 
 The author's classification is, of course, subject to modification. 
 He has, however, taken into account the chief characters of infections 
 without neglecting the etiological data. He subdivides all infections, 
 according to the causative agent, into infections of bacterial, mycosic, 
 or animal origin. In a last group are placed those diseases in which 
 the causative agents are as yet unknown. 
 
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30 l yFECTIO US DISEA SES. 
 
 This classification is naturally of a provisional character. Tuber- 
 culosis, for instance, has been placed in its customary position — viz., 
 among bacterial infections. It should, however, be classed with 
 mycosic infections if its agent is an oospora. In view of the contri- 
 butions of Lesage, Achalme, Triboulet, Coyon, Laveran, and Catrin, 
 the author has, with reserve, classed measles, acute articular rheu- 
 matism, and mumps as bacterial infections. Supported by researches 
 which the writer is pursuing with Dr. Weil, and by the more recent 
 work of Funck, smallpox, varicella, and vaccinia have been placed 
 among the diseases due to animal microbes. Finally, dysentery has 
 been divided into two distinct affections which are akin sympto- 
 matically, but different as to their pathogenic agents. 
 
 Tumors and lymphadenia are excluded, although their parasitic 
 nature seems highly probable. 
 
 In this tentative classification of infectious diseases the actual 
 process alone is taken into account, viz., that which is connected 
 with the life of the pathogenic agent. When the latter is destroyed 
 the morbid evolution does not stop. Here is brought to light an 
 interesting difference between parasitic and infectious diseases: in 
 the former all symptoms vanish with the parasite; in the latter 
 certain disturbances persist and run an independent course of evo- 
 lution. Organic affections, which are often developed in a slow, 
 insidious manner, are thus created, and in some accidental way a 
 cardiac lesion, for instance, connected with a typhoid fever suffered 
 in childhood, and which has taken fifteen or twenty years to develop, 
 is discovered in the adult. This, however, is of little practical im- 
 portance, since the organic lesion is wholly independent of the causa- 
 tive affection of long ago. The sequelae of infections are, therefore, 
 rightly described as affections of the organs bearing no stamp of their 
 origin. 
 
 History of Infectious Diseases. 
 
 It has always been admitted that infectious diseases may be trans- 
 mitted by the air and by contact with the sick. Hippocrates speaks 
 solely of the former mode, as do also the writers and poets. As late 
 as the sixteenth century no important document concerning the con- 
 tagiousness of disease is furnished us by medical literature. The 
 ancients were not, however, ignorant of the transmission of disease 
 by contact. It was evidently for fear of contagion that Moses ordered 
 the isolation of persons afflicted with leprosy or gonorrhea. It was 
 
GENERA L OONSIDERA 'floss. :>) 
 
 the same etiological notion that, al the end of the fourteenth cen 
 tury, caused in Italy the isolation of persons who had conic in contacl 
 with plague-stricken individuals. 
 
 Disregarding the useless controversy which raged about the que* 
 tion of the contagiousness of diseases, lei us briefly review the idea* 
 which successively prevailed as to the nature of the principle* thai 
 served for their transmission. 
 
 Two great theories have always been advocated. One, the chemi- 
 cal, assumes the cause of diseases to be a volatile or fixed principle 
 emanating from the soil, bodies of animals, or men. The other, a 
 vital one, asserts the action of infinitely small living beings which 
 penetrate and develop within the organisms of men or animal-. 
 
 Some of the advocates of the chemical doctrine thought the mor- 
 bific principles were volatile. This conception was so deeply rooted 
 that Henry VIII. caused his Minister (Wolsey) to be tried for having 
 spoken into his majesty's ear; he accused him of an attempt to 
 transmit syphilis to him through the agency of his breath. Syden- 
 ham and Cullen believed that contagion was effected by vapors rising 
 from the human body. However, the practice of variolization and 
 vaccination clearly demonstrated that the viruses were not always 
 volatile. The profession was thus led, at the beginning of the nine- 
 teenth century, to admit two orders of contagion : one volatile, that 
 is, the air charged with putrid vapors; the other fixed, multiplying 
 within the organism. 
 
 What, however, is the nature of this fixed virus? Fracastor had 
 already compared the development of disease to putrefaction, with- 
 out, of course, suspecting the animate origin of the latter process. 
 He thought that germs developed and served for the propagation 
 of the malady. The same idea was taken up by Henle (1840), who 
 believed that contagious diseases were due to organic particles eman- 
 ating from the living organism and preserving their pathogenic 
 power. Ch. Robin's theory hardly differed from the preceding one : 
 "Virulent diseases are those in which the fundamental organic sub- 
 stance or substances of one or of all the humors have undergone a 
 specific modification, which modification is transmitted to organic 
 substances themselves and then to the organized substance of an- 
 other living being. ... As to the creation of the virulent state, 
 it is the same phenomenon as the one that occurs for the formation 
 of the organic substances themselves by isomeric catalysis. 1 " That 
 
 1 l.ittre et Robin. Diet, de mod., art. Inoeulable et Virulent. Pari-. 1878, 14th ed. 
 
32 I HTFE( 'TIOl 's DISEASES. 
 
 norma] substances should undergo analogous alterations on coming 
 in contact with some modified organic matter was not far from con- 
 ceivable; but the doctrine fails to explain the appearance of the 
 modified state. It does not offer an acceptable theory by comparing 
 the development of virulent diseases to the formation of organic 
 substances. This brought into the domain of pathogenesis the cur- 
 rent ideas upon spontaneous generation. Even the great discovery 
 <>f Villemin did not suffice to overthrow the erroneous theories, as 
 it only established the transmissibility of tuberculosis from sick to 
 healthy individuals. Although of great importance from the stand- 
 point of hygiene and prophylaxis, it did not reveal the nature of the 
 pathogenic agent. 
 
 Even previous to this epoch, however, certain minds were im- 
 pressed by the analogies existing between the development of infec- 
 tious diseases and that of animals and plants. It was merely a com- 
 1 larison, but was destined to be a highly fertile one. Solid arguments, 
 however, did not appear until the beginning of the nineteenth cen- 
 tury. By a sort of divination, some minds began to perceive the 
 truth. Hildebrand, in his book on contagious typhus (1811), showed 
 that miasms spread and multiplied like the germs of living beings. 
 About the same period J. Hamean, a country physician, to whom 
 is due one of the first observations of the transmissibility of glanders 
 from the horse to man, argued that virulent matters possessed a life 
 principle, since they acted like parasitic insects. He further stated 
 that there is an antagonism between certain viruses, such as variola 
 and vaccinia, and transitory viruses, such as scarlatina, and the 
 bodies which they leave, since they attack them no more — i. e., confer 
 immunity. It must be admitted, therefore, that viruses produce 
 within the body excrementitious substances which, so long as they 
 are not eliminated, inhibit their action. Hamean thus perceived the 
 mechanism of acquired immunity as it is admitted at present. 1 Budcl 
 asserted (1850) that cholera was transmitted by germs, and, in 1870, 
 he assumed that living organisms represented the specific cause of 
 contagious diseases. Bouillard accepted the same idea, and Trous- 
 seau, in a famous lecture, showed that infectious diseases were trans- 
 mitted by living germs: "The facts of contagion," said he, "would 
 thus materially be explained, if the presence of these spores in the 
 atmosphere could be discovered. To attain this result one should 
 
 1 J. Hamean. Etudes sur les virus (1836-1847). Edition preceded by a preface 
 by Prof. Grancher, Paris, 1895. 
 
QENERA l< CONSIDERATIONS. 33 
 
 follow the path traced by M. Pasteur and proceed with the 
 experimental ability and patience." 1 II. Gueneau de Mussy (1878), 
 in his preface to the translation of Murchison's booh on typhoid 
 fever, pleads in favor of the parasitic doctrine and points oui the 
 respective parts played by the seed and the soil. 
 
 However, these pathogenic conceptions, which were arrived at by 
 reasoning, were to be followed and confirmed by bacteriological 
 researches. The first step was to attribute infections to relatively 
 highly organized parasites. Van-on and Columelle speak of diseases 
 engendered by insects spread in the air. In the sixteenth and seven- 
 teenth centuries analogous ideas were developed by various obser- 
 vers. Infusoria were described by Languis for measles; by Zacutue 
 for smallpox; by Kircher for the plague. On the other hand, Lancisi, 
 Reaumur, and Linne supported with their great authority the ani- 
 mate nature of contagions. Deidier admitted the agents of syphilis 
 to be worms; Goiffon (of Lyons), in 1721, believed that invisible 
 insects transported the plague. This coarse parasitism reached its 
 height with Raspail. 
 
 The true pathogenic agents had, however, been seen as earl}- afi 
 1850. In that year Rayer communicated to the Societe de Biologie 
 observations which he had made with Davaine upon the blood of 
 sheep infected with anthrax. By examining under the microscope 
 a drop of blood derived from the dead animal, they had seen "minute 
 filiform bodies about twice as long as the diameter of a red blood 
 corpuscle. These little bodies presented no spontaneous move- 
 ments." Pollender and Brauell rediscovered these same elements. 
 Delafond, in 1860, considered them as plants and attempted to cul- 
 tivate them, and even endeavored to demonstrate the spores. He 
 failed at the latter point. The existence of anthrax spores was to 
 be demonstrated sixteen years later by Robert Koch. 
 
 In spite of the important discoveries which enriched the history 
 of anthrax, no one had understood the pathogenic role of the rods, 
 to which a prognostic value alone was attributed. The true concep- 
 tion was gradually attained in an indirect manner by the study of 
 fermentations. Rhazes, Hoffmann, Bressy, and others compared 
 infections to fermentations, a comparison of great interest. Unfor- 
 tunately, however, the cause of fermentations was just as little 
 understood as was that of infections. 
 
 1 Trousseau. De la contagion. Clinique med. de l'Hotel Dieu. t. i p. 593-622. 
 
 3 
 
34 l.MECTIOUS DISEASES. 
 
 The fact is that an erroneous doctrine, prevailing since the time 
 of Aristotle, prevented advance along this line. Reference is here 
 made to the idea of spontaneous generation. Redi, in 1668, was 
 the first to rise against this dogma. Transporting the problem 
 to experimental ground, he showed that the larva 1 of flies were 
 not born spontaneously through putrefaction of meat. When the 
 insects were prevented from depositing their eggs no larvse could 
 develop. 
 
 Soon after, in 1678, van Leeuwenhoek discovered in infusions 
 minute animals which Wrisberg, in order to indicate their origin, 
 named infusoria. Van Leeuwenhoek admitted that these minute 
 beings floated in the atmosphere, but his view was not acceptable 
 to all. and his researches became the subject of memorable contro- 
 versies, principally between Needham and Spallanzani. The latter 
 proved by admirable experiments that infusions remained sterile 
 when well protected from the germs of the atmosphere. 1 This dis- 
 covery was confirmed and completed by Schulze and Schwann at the 
 beginning of the nineteenth century. Finally, in 1837, Cagnard- 
 Latour demonstrated the numerical and ponderable increase of yeast 
 in the course of the fermentative process and established its animate 
 nature. Still, Liebig's school persisted in attributing fermentation 
 to the action of some decaying substance. 
 
 Such was the state of the question w T hen Pasteur's researches on 
 the lactic acid ferment (1857), the alcoholic ferment (1860), and 
 finally, on some anaerobic, viz., butyric ferment (1861), were suc- 
 cessively published. 
 
 Pasteur's researches on silkworm diseases (1865-1870) may be 
 considered as the fundamental work from which the era of the new 
 discoveries and doctrines dates. Unfortunately, these researches 
 were ignored or uncomprehended by the medical world. Davaine, 
 however, had surmised that disease as well as fermentation depended 
 upon animate agents, and accumulated a considerable amount of 
 experimental facts in support of this conception. 2 In spite, however, 
 of the admirable investigations of Davaine, and the discovery of 
 
 1 Spallanzani. Observations et exp. faites sur les animalcules des infusions. 
 CEuvres completes (Trad. Senebier), 1787, t. i. Observations et exp. sur l'origine des 
 petites plantes des moisissures. Ibid., t. ii. p. 286-309. 
 
 2 Davaine. Recherches sur les infusoires du sang dans la maladie connue sous le 
 nom de sang de rate. Comptes rendus, 1863. Davaine published a great number of 
 notes inserted into the C. R. of the Academy of Science, Academy of Medicine, and 
 Society of Biology. They are collected in l'GEuvre de Davaine, Paris, 1889, t. i. 
 
GENERA L CONSIDERS TI0N8. ;;.". 
 
 anthrax spores by Koch,' the p;ir;isitic theory of infectiou di 
 had few adherents. Further opposition was rendered impoi >\' 
 however, when Pasteur, 2 by the method of culture . demon trated 
 beyond all doubt that anthrax is caused by the bacillus anthracie 
 as scabies is caused by the acarus scabiei. A few years Inter bacte- 
 riological doctrines received official sanction a1 the Paris Faculty of 
 Medicine by Prof. Bouchard, who was the first to study the role 
 played by animate agents in the genesis of infections. 
 
 This was in 1880 and [881, when reaction was intense. Opposition 
 gradually gave way to successive discoveries which established be- 
 yond dispute that infections are due to parasites some vegetable, 
 others animal, most of them of a bacterial nature. 
 
 Classification of Infectious Agents. 
 
 Pathogenic Bacteria. For reasons already referred to we cannot, 
 as do some authors, regard "infectious" and "bacterial" diseas 
 synonymous. Admitting, however, the considerable pathogenic role 
 of bacteria, we shall begin the history of pathogenic agents by a study 
 of them. 
 
 At present bacteria 3 are generally considered as belonging to the 
 family of algae, and not, as was formerly believed, to that of the fungi. 
 Hence, the name schizophycetes 4 would be more suitable than schizo- 
 mycetes, 5 generally employed since Naegeli's time. 
 
 From a purely medical standpoint, bacteria are divided into two 
 groups under the names saprophytic and pathogenic, according as 
 they develop in dead or in living organisms. Though highly im- 
 portant, this division is not complete. We think it is well to add a 
 third group — that of parasitic bacteria — which vegetate upon living 
 organisms without inflicting any appreciable harm. It is also to be 
 
 1 R. Koch. Die Aetiologie der Milzbrand-krankheit. Cohn's Beitr. zur Biol, der 
 Pflanzen, 1S76. 
 
 2 Pasteur, Joubert, Chamberland et Roux. Numerous notes published in the 
 Comp. Rend, of the Academy of Science, beginning with 1877. 
 
 3 Bacterium (from .lanrtipiov, a little stick, diminutive of Sanri/pia, a stick, staff. 
 plural, bacteria) is a general name applied to microbes entering the group of schizo- 
 phytes. The term bacterium should not be employed as synonymous with microbe. 
 The latter (JSlinpoc, small, 3ioc, life") is used to designate all microscopic beings of vege- 
 table or animal nature. 
 
 4 Schizophycetes (oxKsiv, cleave, split: error, plant), alga; which multiply by 
 division or fission. 
 
 5 Schizomycetes (ty^ftfetv, to cleave. Mvtajr, pi. Mwra/rej-j a fungus), fungi which 
 multiply by cleavage or fission; hence fission fungi. 
 
36 I SFECTIOUS DISEASES. 
 
 remembered that the same bacterium may sometimes be a sapro- 
 phyte and at times a parasite, and on other occasions rise to the rank 
 of a pathogenic agent. It is true that there are bacteria which, thus 
 far, have always seemed to be devoid of virulence, and their cultures 
 injected into animals, even in large doses, induce no disturbance. 
 There are, however, others which are capable of passing from the 
 state of a saprophyte to that of a pathogenic agent; and, recipro- 
 cally, the majority of infectious bacteria may have a saprophytic 
 life. It is not, therefore, indulging in pure hypothesis to admit that 
 microbes have accidentally become morbific and that it is by accident 
 that they pass from a saprophytic to a pathogenic life. 
 
 In view of these facts, some preferred to classify microbes according 
 to other characters, notably their biological properties. Pasteur, who 
 attached little importance to morphology, considered fermentative 
 processes of far greater consequence. He believed that by studying 
 the modifications which microbes produced in well-defined products 
 it was possible to reach a sure classification. Fermentative action, 
 however, has no fixed characters. Several different bacteria may 
 give rise to the same products. Moreover, within a well-defined 
 species are found varieties enjoying similar fermentative powers. 
 Finally, by means of successive cultures the action upon media 
 may be modified. 
 
 There is, however, an action which is considered by most authors 
 to be of considerable diagnostic importance, viz., the peptonization 
 of gelatin. Hence, the majority of bacteriologists divide microbes 
 into those which liquefy gelatin and those which do not. This char- 
 acter is evidently of real interest, but there is no reason for attrib- 
 uting to it an absolute value sufficient to separate species which, 
 in other respects, seem to be closely allied. 
 
 A natural classification of bacteria requires cognizance of the 
 greatest possible number of characters. Such an attempt, at the 
 present stage of the science, is premature. It is better to be guided 
 by some objective character of sufficient constancy and appreciable 
 without much difficulty. Accordingly, the majority of authors have 
 taken morphology as a basis. 
 
 Without enlarging upon all classifications that have been proposed, 
 the author believes that bacteria may be grouped in the following 
 simple manner: 
 
Corel 
 
 GENERA l, 00N8IDEBA 'floss. :>,, 
 
 I >iploco< 
 
 I I tracoi 
 
 - 1 |. p| .,<•.,<■..! 
 
 Stapi 
 
 Mei i mop difl . 
 
 Leuconi 
 
 \ ecu 
 
 Bacilli(rod-shaped) 
 
 I mum 
 
 Bacillu 
 l <epto1 in i •. 
 I • 
 
 ( Irenol liri x. 
 Cladol liri \ . 
 
 Vibrion. 
 Curved bacteria j Spirillum 
 
 ' Bpirochast •■> . 
 
 Cocci (x°XX°Z) berry, grain) ;m> round elements, almost always 
 
 non-motile and sporeless. According as the elements arc isolated or 
 agminated, they are called monococci, diplococci, and tetracocci; 
 
 when in the form of a chain, streptococci, and when presenting the 
 shape of grape bunches, staphylococci. These divisions are of no 
 great importance, since the same species may appear under several 
 aspects. It is true, however, that it assumes by preference one of 
 these aspects which serves as its characteristic feature. 
 
 The merismopedise are constituted by cells or plates arranged on 
 a plane. In sarcina? the mode of division is peculiar. It has three 
 planes of division. Leuconostoc and ascococci are of little importance 
 from a medical standpoint. 
 
 The group of rods contains, in the first place, the bacteria and 
 bacilli. The former are short and often ovoid in form; the latter are 
 cylindrical. This distinction, however, is gradually being displaced, 
 and the term bacilli is now almost universally employed. 
 
 The leptothrix occurs in the form of a more or less segmented 
 filament. The crenothrix presents the same aspect, except that it 
 is surrounded by an envelope. The cladothrix is characterized by 
 the presence of lateral filaments, so that some authors have taken 
 it to be a higher organism than the bacteria and confounded it with 
 the streptothrix. In an important contribution, Sauvageau and 
 Radais demonstrated that in cladothrix there are no real branchings. 
 There are only new elements, produced by fission, which remain 
 attached to each other. They constitute a colony, not an individual. 
 It is important to emphasize this point, since authors often confound 
 the two, and it is not clear whether they refer to cladothrix or 
 streptothrix. 
 
38 INFECTIOUS DISEASES. 
 
 The third and last group is composed of curved elements. Some 
 have the shape of a comma or of an S. These are the vibrios. 
 Others present the form of spirals. When the screw-like turns are few 
 in number and less close, the elements are called spirilla; when the 
 contrary is the case, they are sometimes designated as spirochete. 
 
 It is often a matter of difficulty to clearly indicate the respective 
 value of characters attributed to various groups. For instance, it 
 is generally admitted that there are numerous analogies between the 
 colon bacillus, the pneumobacillus, and the typhoid bacillus. One 
 might add even the bacillus of pseudotuberculosis of rodents. Should 
 these various types be considered as distinct, though allied, species, 
 or, on the contrary, do they represent varieties that may be trans- 
 formed into each other? The delicate question has long been the 
 subject of controversy. Moreover, the colon bacillus and pneumo- 
 bacillus vary extreme^ in form, biological properties, and pathogenic 
 potency. We are, therefore, led to presume that these species com- 
 prise numerous varieties which have often been described as new 
 species. 
 
 Over two hundred pathogenic bacteria are actually known. They 
 may, in this respect, be divided into two groups according as they 
 produce a well-defined disease or give rise to various pathological 
 processes. Such a division is in harmony with the expressions 
 "specific" and " non-specific." Taking morphology into account 
 at the same time, we reach the following classification in which the 
 principal species alone are included: 
 
 Xox-specific Bacteria. 
 
 Micrococci. 
 
 /-aureus. 
 Pyogenic staphylococcus . . < citreus. 
 
 lalbus. 
 Streptococcus ..... very numerous varieties. 
 
 Pneumocoecus (Streptococcus pneumonia;) . 
 Tetragenus ...... 
 
 Bacilli. 
 
 falbus. 
 t citreus. 
 
 Colon bacillus 
 
 Pneumobacillus 
 
 B. lactis aerogenes. 
 B. neapolitanus. 
 B. pyogenes fcetidus. 
 B. enteritidis. 
 B. endocarditis griseus. 
 pyobacillus Fischeri. 
 B. cavicida. 
 
 septic bacillus of the bladder, 
 pyogenic bacterium, 
 .paracolon bacillus. 
 B. of rhinoscleroma. 
 B. hominis capsidatus. 
 B. capsulatus septicus. 
 B. endocarditis capsidatus. 
 
( ; E A' EBAL 00 NS TDERATIO N8. 39 
 
 r>. of f > i i baoosis. 
 
 I:, of bemorrh sepl Lcemiae. 
 
 li. aepticua putidus, 
 
 ■ /■/ .,/. // in u niiii i . 
 Proteus vulgaris .... Proteu pleomorphu . 
 
 i /', ,,/, ,/ , /it ,i a . 
 
 15. of (lysciilciifonn enteritis 
 
 B, pyooyaneus . . . . | ,, 
 
 Lepfoflirix I > 1 1 f - < • . 1 1 1 
 
 Specii to B \< i lima. 
 
 Micrococci. 
 
 ( lonococcus 
 
 Diplococcua intract llularis meningitidis 
 
 Micrococcus of iiniiiips 
 
 Bacilli. 
 
 B. anthracia ...... several experimental varieties. 
 
 ....,,.,, f pseudodiphtheria 1 1 
 
 DipMhenaB. . {% hoTt B.(1) 
 
 B. of glanders 
 
 Typhoid 1>. 
 
 li. of influenza 
 
 Tubercle bacillus (perhaps to be placed i human B. 
 
 among the streptothrix) ... B. of ih<- gallinas. 
 
 I B. offish. 
 B. of leprosy. 
 B. of pseudotuberculosis. 
 B. of bubonic plague. 
 B. of yellow fever. 
 B. of soft chancre. 
 B. of tetanus. 
 
 B. of gaseous gangrene . . . . B. of symptomatic anthrax. 
 
 B. of rheumatism. 
 Spirillus of recurrent fever. 
 Vibrio of Asiatic cholera. 
 
 The Infectious Fungi. As already stated, infectious dis< 
 may be caused by plants more highly organized than schizophycetae. 1 
 The streptothrixse will first be mentioned. Of these a dozen are at 
 present known, several of which are pathogenic. More frequently, 
 however, they induce local lesions only. There are in this group four 
 plants which are capable of giving rise to genuine infectious diseases. 
 
 In the first place, there is Noccirdia Jarcinosa, which produces a 
 malady known as farcina bovidce. It was discovered by Nocard, who 
 at first considered it to be a cladothrix. It causes in bovidse lympha- 
 gites and suppurating adenites, which are not to be confounded with 
 true glanders, a disease from which bovida? are immune. 
 
 Oospora asteroides, discovered by Eppinger (1891) in a cerebral 
 abscess, was again found by Almquist in a case of meningitis, by. 
 Ferre and Faguet in an abscess of the brain, by Sabrazes and Rmere 
 in a cerebral abscess and in a suppurating infarct of the kidney. 
 
 1 For the study of these diseases consult: W. Dubreuihl, L^s moisissures para- 
 sitaires de l'homme et des animaux superieurs. Arch, de ni6d. exper.. 1891, p. -42S and 
 566. Blanchard. Les parasites vegetaux. Traite" de path. gene>ale. 1S96. t. ii.p. 811. 
 
40 lyFECTIOUS DISEASES. 
 
 Actinomyces (Nocardia bovis. slreptothrix actinomyces, oospora 
 bovis), tin 1 most important agent of this group, is pathogenic for 
 both man and various mammalia, notably bovidae.- It may be con- 
 sidered as the type of higher agents capable of producing infectious 
 diseases. 
 
 Phycomyces are fungi which constitute a transition with the algae. 
 They include oomyces and zygomyces. Among the former is found 
 leptomitus, which is pathogenic for insects and is also encountered 
 in man. In the majority of instances, however, it is a simple parasite. 
 
 Zygomyces comprise the entomophthorae and the mucedinie. Fur- 
 bringer reported two cases in which the pulmonary foci were due to 
 mucor mucedo. The case reported by Paltauf 1 is more interesting: 
 The patient, a man, fifty-two years of age, succumbed nine days 
 after his admission into the hospital with very serious general symp- 
 toms: fever, icterus, diarrhoea, tumefaction of the liver, and spleen, 
 typhoid state, and coma. At the necropsy there were found intes- 
 tinal ulcerations, foci of pneumonia, cerebral abscesses, and suppu- 
 rative laryngitis and pharyngitis. These various lesions were due to 
 a parasite which appeared to be the mucor corymbifer. Experimen- 
 tation further demonstrated that this vegetable was pathogenic for 
 animals (Lichtheim). 
 
 The mycomyces are fungi of a low order comprising an important 
 group, viz., the ascomyces. In fact, it is in this group that yeasts 
 are classed. Experimentation demonstrated the existence of a great 
 number of yeasts that are pathogenic for animals. A few observa- 
 tions tend to establish the same to be true with regard to man. This 
 subject will be discussed in a separate chapter. 
 
 Finally, there are the perisporiacse which comprise aspergillinse. 
 These frequently produce lesions in the respiratory organs of birds 
 (A. C. Mayer, Robin, Bouchard, Hayem, etc.). Aspergillus fumiga- 
 tus may cause various lesions in man, such as cutaneous suppura- 
 tions, a special form of onychomycosis, suppurations of the cornea, 
 or lesions in the ear (otomycosis). In the latter case other parasites 
 may also be encountered such as aspergillus nigricans, aspergillus 
 flavescens, aspergillus nidulans, eurotium repens, etc. 
 
 Such are the principal mycoses observed in man. Their number 
 is not considerable, as may be seen from the following list represent- 
 ing the main vegetable agents thus far discovered: 
 
 1 Paltauf. Mvcosi- mucorina. Em Beitrag zur Kenntniss der menschlicben Faden- 
 pilzerkrankungen. Virchow's Archiv, 1885, Bd. cii., p. 543. 
 
ENEBA l. < 'ONSIDERA TI0N8. 1 1 
 
 Odspora asteroides (Streptothrix and Nocardia) 
 " bovis (ad inomyoee). 
 " madurcB. 
 
 \l iimr lit iimln. 
 
 " corymbifer. 
 oiiliiim albicans (Endomycea albicans, Vuillemin), 
 
 " siibtilr. 
 
 Aspergillus fumigatus. 
 
 ] have excluded all those vegetable agents which behave in man 
 as simple parasites. For the present ii is sufficienl to have shown 
 that plants other than bacteria are capable of producing infections 
 
 in num. 
 
 Infectious Protozoa, [nfections due to protozoa are extremely 
 frequent in the lower vertebrates, fish, the batracian, and in verte- 
 brates. The same is probably true with regard to man and higher 
 vertebrates, as some recent researches tend to demonstrate. 
 
 Of the four classes of protozoa, two only are of interesl to us: 
 the rhizopodes and the sporozoa. Among the former are t he amoebae, 
 of which three varieties are met with in man. These are designated 
 according to their seat, as A. gingivali*, A. var/inalis or urnyi'iiihili*, 
 and A. intestinalis. The last is undoubtedly the most important. 
 Numerous contributions tend to demonstrate that it is the causative 
 agent of an important variety of dysentery and even of certain 
 abscesses of the liver. Several observations have been reported in 
 which amoeba? alone were found in hepatic suppurations consecutive 
 to dysentery. The author published, with Dr. Peyrot, a case of this 
 kind. It may, however, be presumed that ordinary pyogenic micro- 
 organisms existed at a certain moment and finally disappeared. 
 Experimental pathology must, therefore, be resorted to in order to 
 secure further information as to the pathogenic power of amoebae. 
 Marchoux succeeded in producing serious dysentery and hepatic ab- 
 scesses in cats by introducing dysenteric dejecta into their digestive 
 organs. These symptoms do not appear when the same dejecta are 
 employed after subjecting them to a temperature which kills the 
 amoebae without affecting the accompanying bacteria. 
 
 The sporozoa comprise several groups, among which are found 
 myxosporidia, sarcosporidia, and coccidia. The importance of the 
 last-named group is constantly tending to increase. They are 
 frequently met with in the liver of rabbits, where they invade the 
 biliary passages and induce epithelial and connective tissue pro- 
 liferations. Malassez encountered forms resembling the so-called 
 colloid cells of epithelioma, the particular granula of moUnscum 
 
42 INFECTIOUS DISEASES. 
 
 contagiosum and of vegetating follicular psorospermosis. These 
 results are evidently of great importance in favor of the coccidian 
 theory of psorospermosis and cancer, but the question is far from 
 settled. 
 
 There has been described under the name coccidium hominis a 
 parasite giving rise to intestinal ulcerations and often to a fatal 
 cachexia. The karyophagus hominis of Podwyssotski induces pig- 
 mentary atrophy of the hepatic cells and secondarily gives rise to 
 proliferation of the interstitial tissue. 
 
 Sporozoa also comprise the group of gymnosporidia of which, from 
 the standpoint of infectious pathology, Plasmodium malaria is of 
 chief importance. As is well known, this parasite, discovered by 
 Laveran in 1881, is the cause of malarial fever. 
 
 Finally, should trichinosis be considered an infectious disease? 
 The symptoms are evidently serious enough to deserve this denom- 
 ination. In its first stage it develops like a true infection, and, in 
 fact, it is most frequently confounded with typhoid fever. Be that 
 as it may, the essential point established is the fact that there are 
 infections due to animal microbes, and if doubt as to some instances 
 is still possible, there can be none with regard to malaria — the disease 
 which all clinicians consider infectious and of which the animal origin 
 was demonstrated beyond all dispute by Laveran's great discovery. 
 
(Ml A PTE R II. 
 GENERAL CHARACTERS OF PATHOGENIC BACTERIA. 
 
 Polymorphism <>f Bacteria, Variability of Their Different l unction SH id 
 
 ments, Pigments, and Pathogenic Properties. Resistance of Bacteria to Destructive 
 Agents. Action of Mechanical, Physical, .'mil Chemical Agents. Action of High 
 
 Pressures, I 1 1 ■ : 1 1 , Cold, l.ii'lil, Kleet rieil v, Soluble Sill/ t:inr:fiS, and Anti eptic ■ 
 
 Difficulty of Determinism in Microbiology. 
 
 Polymorphism of Bacteria. From the very beginning of I >ac- 
 
 teriology two contrary opinions appeared as to the value of char- 
 acters peculiar to each species. Morphology was taken as a basis 
 for classification. It was, therefore, necessary to determine whether 
 the forms were or were not immutable. Cohn advocated monomor- 
 phism of bacteria, and Naegeli contended for polymorphism. ( hi 
 January 22, 1878, in a communication to the Academic de M£decine, 
 Pasteur rejected morphological classifications, citing, as an illustra- 
 tion, the example of the septic vibrio, which, he said, "according to 
 the media in which it is cultivated, assumes shapes, lengths, and 
 sizes so diverse that the observer might believe them to be repre- 
 sentatives of different species." In spite of the exaggerations of 
 Zopf, polymorphism made considerable progress and found such 
 advocates as Hueppe, Koch, Metchnikoff, etc. 
 
 In studying polymorphism it is necessary to distinguish cultures 
 grown under eugenesic conditions from those grown in media or 
 under influences unfavorable to their development. In the fomer 
 instance morphological variation expresses an adaptation to slight 
 or even hardly noticeable variations of environment : in the latter 
 case it indicates a state of suffering and represents a modification of 
 pathological order. 
 
 Polymorphism under Eugenesic Conditions, This must be Studied 
 in the living animal and in artificial cultures. 
 
 Pasteur indicated the variations of shape which the septic A'ibrio 
 undergoes in the animal body. At the point of inoculation are found 
 thick and short bacilli; in the peritoneum, and particularly near the 
 surface of the liver, long, slender filaments are encountered. This 
 result may readily be explained: The conditions of vegetation are 
 
44 INFECTIOUS DISEASES. 
 
 not the same in the more or less dense cellular tissue into which the 
 injection is made and in the peritoneum where nothing hinders the 
 development of the microbe. 
 
 By sowing. the same microbe on different media dissimilar forms 
 are often obtained. For instance, the bacillus of dysenteriform 
 enteritis appears in the infected organism in the form of thick rods, 
 resembling somewhat the bacillus anthracis, and measuring from 5f- 
 to 6/t in length and from 1.3;" to 1.5," in breadth. In bouillon they 
 are more slender. In agar-agar they do not exceed 0.5,« by 2// when 
 the culture is twenty-four hours old; on the days following they are 
 not more than l;x or even 0.5/* in length and 0.5/* in thickness. 
 Upon vegetables they are still shorter and more slender, and a few 
 have an oval shape. 
 
 AVhat may seem more curious is the fact that microbes may present 
 different shapes in the same medium. In such cases the change is 
 generally due to old age, the morphological variations corresponding 
 to the various stages of their evolution. In other instances a modi- 
 fication of the medium is to be attributed to the life of the micro- 
 organisms. The bacteria absorb nutritive substances and produce 
 ferments or excrete toxins which modify the constitution of the 
 medium. The medium being thus modified, an adaptation on the 
 part of the microbes is necessitated, resulting in morphological 
 changes. So-called involution forms, which consist in swellings com- 
 parable to pears, clubs, bottles, etc., are observed, especially in old 
 cultures in which the nutrient medium is exhausted or adulterated. 
 
 Polymorphism of the Buccal Tetracoccus. In studying the throats of 
 patients suffering from simple or scarlatinal angina I have often 
 found a microbe whose polymorphism may lead to confusion. This 
 microbe, analogous to, if not identical with, tetragenus, is of very 
 frequent occurrence in the mouths of scarlatinal patients. I have 
 discovered it in 85 per cent, of such cases. The proportion is 69 per 
 cent, in other sore throats, and 52 per cent, in diphtheria. This 
 same microbe very often inhabits the throats of normal individuals 
 and the buccal cavity of various animals, such as dogs, rabbits, 
 guinea-pigs, and mice. At times it can be recognized by direct exam- 
 ination, that is, when it presents the form of typical tetrads sur- 
 rounded with capsules. Its morphological variations, however, are 
 considerable, and it not infrequently occurs in the form of diplococci 
 or is arranged in small heaps of round elements in nowise charac- 
 teristic. The polymorphism of the tetracoccus is also marked in 
 
GENERAL CHARACTERS OF PATHOGENIC BACTERl 1. |,, 
 
 cultures. This morphological variability might, at fir t, lead to the 
 belief that h is merely a question of accidental contamination. 
 The writer has convinced himself that such is nol the ca i 
 by certain procedures it is possible to cause Hie microbe in que 
 to pass from the zoogleic to the tetracoccic form, and vim <•■ 
 
 The microbe of i he author differs from the classical tetragenue not 
 only by its polymorphism hut also by its action upon animals 
 Unlike tetragenus, it, is not pathogenic for rabbits, and very slightly 
 so for mice. In sufficiently high doses, it produces vry strange, 
 nervous disturbances in rabbits. 
 
 It is, therefore, difficult to determine whether t his mien, he ig iden- 
 tical with the classical tetragon us or not. In order not to prema- 
 turely announce its nature, the author proposes to provisionally 
 designate it under the name of buccal tetraeoccus I h/rarorru. 
 buccalis). At all events, the name tetraeoccus is more in harmony 
 with that of tetragenus in bacteriological terminology. 
 
 If, in spite of its great frequency in cases of sore throats, this 
 microbe has not yet been brought to notice, it is owing to the fad 
 that it develops poorly upon serum and that its polymorphism has 
 caused it to be confounded with other microbes, notably with t he- 
 streptococcus. This confusion can be avoided by taking into account 
 the characters above indicated. In doubtful cases it is well to trans- 
 fer a colony to gelatin. This medium, which is rapidly liquefied by 
 the streptococcus, remains solid under the action of the tetracoccu.-. 
 
 Other examples might be quoted, but those above referred to 
 suffice to show how numerous are the morphological variations pre- 
 sented by bacteria in the course of their development in the same 
 medium. Analogous differences are also observed according as solid 
 or liquid culture media are employed. In liquid media the microbes 
 generally grow in length and group themselves in a different manner. 
 This is not surprising. The stud} 7 of plants of low organization, 
 'notably alga?, furnishes similar examples. Not to leave the field of 
 pathogenic agents, it will suffice to recall oidium albican*. According 
 as this plant is grown in agar-agar or in bouillon, oval or the fila- 
 mentous forms predominate. 
 
 Polymorphism under Dysgenesic Conditions. The variations mani- 
 fested b} 7 bacteria are still more curious when the latter are placed 
 under conditions unfavorable to their development. In this connec- 
 tion it will be interesting to examine the influence of mechanical 
 agents, and to determine, for instance, whether morphology is the 
 
46 INFECTIOUS DISEASES. 
 
 same when the culture is undisturbed or is agitated. As to physical 
 agents, the role of heat alone has thus far been studied. It is known 
 that the finest involution forms are obtained by placing the cultures 
 in overheated media. The role of chemical agents has received more 
 attention. Drs. Guignard and Charrin full}'' demonstrated the pro- 
 found modifications presented by the bacillus pyocyaneus when cul- 
 tivated in media to which antiseptic substances have been added. 
 The bacillus then lengthens and assumes a filamentous form, or it 
 rolls up into the shape of spirilla, or its size is reduced to such an 
 extent as to resemble micrococci. These curious results were con- 
 firmed b} 7, Wasserzug's researches. 
 
 Under the same conditions many other microbes present morpho- 
 logical variations. In this respect the most remarkable microbe is 
 the B. prodigiosus. When grown upon gelatin containing 2.5 to 3 
 per cent, of boric acid, it produces a magnificent spirilla having ten, 
 twelve, and even sixteen or twenty turns; each turn of the spiral 
 has a length of about 1.5//; then on the fourth day involution 
 forms appear which occupy the central part or the end of the 
 spiral. 
 
 With the atypical variety I obtained in the same medium filaments 
 varying in length from 15// to 120// and even 180//. Toward the 
 tenth day these filaments became segmented and gave rise to motile 
 bacilli; at the same time involution forms appeared. 
 
 If a portion of these peculiar cultures is transferred to the usual 
 media, colonies are obtained in which the microbes resume their 
 normal form. The modifications imposed by antiseptics are, there- 
 fore, transitory. Wasserzug believed, however, that he had obtained 
 an actual transformation and fixation of new characters. In reality, 
 it is not possible to create by these procedures anything more than 
 varieties comparable to the varieties observed in higher beings. In 
 other words, we cannot transform the species. 
 
 As to the capsules which surround certain microbes, it must be 
 stated that they are scarcely of any morphological and diagnostic 
 importance, since they are quite inconstant. 
 
 Variability of the Functions of Bacteria. The experimenter 
 may produce functional variations in microbes. He can modify 
 their mode of reproduction, and by means of chemical agents he can 
 create asporogenic varieties. Such, for instance, is the case with 
 the bacillus anthracis. 
 
 Pasteur believed it was possible to characterize and classify 
 
GENERAL CHARACTERS OF PATHOGENIC BACTERIA. 17 
 
 microbes by a study of their action upon fermentable sub tai 
 Eowever, in this respect, also, the results are nol con tant. For 
 instance, let us examine the action of the colon bacillus upon milk. 
 The typical examples of this microbe coagulate milk because they 
 attack the lactose, producing fermentation, and thm rendering the 
 medium acid. There are, however, other varieties of colon bacilli, the 
 paracolon bacillus of Gilbert, which do no1 coagulate milk. The 
 author has observed a colon bacillus derived from a gangrenous 
 pleurisy which did nol at first acl upon milk. On cultivating it in 
 inert media, it was noticed that the medium was slowly rendered 
 acid. It took a week to produce a little deposit of casein; two 
 months later the same microbe completely coagulated milk in 
 twenty-four hours. Here, therefore, is a variety that passed from 
 the group of paracolon bacilli to that of the typical colon bacillus. 
 
 Similar results are obtained with yeasts. The transformation of 
 sugar varies according to the aeration of the medium. The yeast 
 plant, when living in the air, consumes free oxygen, multiplies rapidly 
 and oxidizes the sugar almost without forming any alcohol. In its 
 anaerobic life it is compelled to abstract oxygen from the sugar, 
 which it then transforms into alcohol and carbonic acid. 
 
 Bacterial Ferments. The action of microbes upon sugar and albu- 
 minoid substances is also variable and differs according to the species 
 employed, the age of the cultures, the nature of the medium, etc. 
 Vignal called attention to the important role of pabulum furnished 
 to bacteria. By adding certain substances to the culture medium the 
 microbe can be made to secrete ferments which affect the substances 
 introduced. There is only one secretion which seems never to un- 
 dergo any variation, namely, that ferment which peptonizes gelatin. 
 It is known that many authors consider the liquefaction of this sub- 
 stance as of importance in bacterial diagnosis. It is, in fact, one of 
 the most stable properties and, consequently, one of those which are 
 of considerable importance in classification. 
 
 Variability of Bacterial Pigments. Aside from the ferments, 
 bacteria secrete various products, some of which may serve for iden- 
 tification of the species. Pigments are the most important of such 
 products. A great number of microbes color the culture media yel- 
 low, red, green, and more rarely blue or violet. This chromogenic 
 function is extremely variable. Certain microbes produce pigments 
 in certain media. Thus the bacillus of glanders and the colon bacillus 
 yield patches of a deep brown color when grown upon potatoes. The 
 
48 ISFECTIO US DISEASES. 
 
 colon bacillus, unlike the typical bacillus, produces a superb green 
 color on slices of artichoke. 
 
 Under various circumstances certain chromogenic microbes may 
 cease to produce pigment. For instance, B. prodigiosus when grown 
 in agar-agar secretes a beautiful red pigment. If transferred to 
 bouillon it does not color the medium; or to speak more accurately, 
 certain cultures do not color bouillon, while others do color it red 
 or rose. 
 
 By modifying the physical conditions of development, the produc- 
 tion of pigments may easily be modified. Schottelius has shown that 
 B. prodigiosus produces very little, if any, pigment, even in agar- 
 agar, if the culture is kept in an incubator at a temperature of 
 100.4 F. (38° C.) or 102.02° F. (39° C). Under these conditions the 
 majority of colonies are white. If, however, this colorless culture be 
 grown at a lower temperature, it becomes rose-colored, then red. 
 
 Analogous results are obtained by preventing the access of air. 
 The author has shown that a culture of B. prodigiosus grown under 
 oil remains colorless. When it is subsequently brought in free con- 
 tact with air, color appears. 
 
 The most interesting modifications are those caused by addition 
 of soluble or insoluble antiseptics to the culture bouillon. 1 Several 
 of these substances first act upon the function of the microbe. In 
 small amounts they hinder or arrest the development of coloring 
 substance; in larger amounts, they hinder or arrest development; 
 finally, their action may still be more marked and may kill the 
 microbe. 
 
 In pursuing the researches on chromogenic bacteria I was able to 
 prevent the production of pigment in B. prodigiosus by adding boric 
 acid to the culture: 2.5 to 5 per 1000 suffices. Staphylococcus 
 aureus produces white colonies when cultivated in gelose containing 
 3 per 1000 iodoform, or 0.6 per 1000 of carbolic acid. These amounts 
 are close to sterilizing quantities, which are 3.5 per 1000 for the 
 former substance, and 0.8 per 1000 for the latter. Finally, I have 
 noted that extremely small amounts of antiseptics stimulate rather 
 than hinder the chromogenic function. In the presence of a trace 
 of corrosive sublimate B. prodigiosus produces a very intense red 
 pigment. 
 
 These experiments are susceptible of infinite variations. The few 
 
 1 Charrin et Roger. Des modifications qu'on peut provoquer dans les fonctions 
 d'un microbe chromogene. Soc. de biologie, Oct. 29, 1887. 
 
GENERAL CHARACTERS OF PATHOGENIC BACTERIA. \u 
 
 illustrations above; referred to suffice to show the influence of the 
 surrounding medium upon the chromogenic function of microbi 
 
 Variability of Pathogenic Properties. Since the research) 
 Pasteur, ii is known thai microbic virulence may very notably be 
 modified. II' a pathogenic microbe is for some time cultivated in 
 artificial media its virulence gradually diminishes and ii sometimes 
 falls to the rank of a saprophyte. Reciprocally, by passing ii suc- 
 cessively through living animals, it is possible to accustom the 
 microbe to a parasitic life; in oilier words, it become- exalted, and 
 in many cases quite considerably. Pasteur's researches further 
 established that a microbe thai has been exalted for one animal 
 species may be found weakened for another. It is also possible to 
 modify virulence by making the cultures under special condition.-, 
 notably by subjecting them to high degrees of temperature, com- 
 pressed oxygen, and chemical substances. These various pro© 
 enable us to create species of definite virulent power, or, as is said, 
 fixed viruses. The bacillus anthracis, for instance, may be culti- 
 vated in such a manner as to be rendered incapable of killing the 
 rabbit or of exerting any action upon even the adult guinea-pig; it 
 can kill only the young guinea-pigs. By progressively graduated 
 passages through a living organism it may recover its virulence. 
 
 It is, therefore, possible profoundly to modify the properties of 
 bacteria, viz., to suppress their sporogenic, chromogenic, and virulent 
 powers. Thus new varieties differing considerably from the original 
 stock and not always surely convertible into it may be created. The 
 functions thus abolished, however, are fonctions de luxe, since, not- 
 withstanding these modifications, vegetation and reproduction may 
 easily be accomplished. It is none the less interesting to note how 
 contingent are the properties of microbes, and how difficult the deter- 
 mination of the species. The uncertainty of bacteriological diagnosis 
 is so great that the same microbe has not infrequently been described 
 under the most varied names. This variability in the characters of 
 microbes is also referable to the fact that cultures are not and can 
 never be uniform. For instance, if a colony of bacillus prodigiosus 
 is diluted with a large amount of liquid and sown on plates, some 
 of the colonies which develop will be red. others rose-colored, and 
 still others white. If a colony apparently uniform — red or white — 
 is diluted and sown, it will again produce dissimilar colonies. This 
 simple experiment clearly demonstrates that all the microbes develop- 
 ing from the same stock are not equally capable of secreting pigment. 
 
 4 
 
50 INFECTIOUS DISEASES. 
 
 The results are identical, though less readily conceivable, with 
 regard to the pathogenic function. All the individuals of the same 
 culture do not possess the same power. It must, however, be recog- 
 nized that by taking certain precautions we can diminish the differ- 
 ences, though we are unable to make them altogether disappear. 
 Hence the necessity of carefully taking into consideration the sources 
 of error connected with these experiments. 
 
 This variability of the elements contained in a culture fluid explains 
 why when this fluid is submitted to the action of some destructive 
 cause the number of microbes is first diminished, but the medium 
 is not completely sterilized. Take, for instance, some pure bouillon 
 culture and count the microbes by means of plates, and then submit 
 the culture to the action of some destructive agent. As all the 
 elements are subjected to the same harmful influence, simultaneous 
 decline of vegetation, weakening of functions, and final destruction 
 are expected. Such, however, is not the case. It will be seen that 
 the number of colonies obtained on the plates diminishes successively, 
 which proves that certain microbes, of weaker resistance, were the 
 first to disappear; but others remain which, unless the conditions 
 are too unfavorable, will overcome the dysgenesic conditions and 
 become more or less perfectly accustomed to them. There occurs, 
 therefore, a sort of natural selection. 
 
 Influence of Various External Agents upon Bacteria. 
 
 Influence of Mechanical Agents. The causes which arrest the 
 development of and destroy microbes are mechanical, physical, or 
 chemical. 
 
 The mechanical causes are represented by the movement of culture 
 fluids. If the fluid is agitated the microbes do not develop or develop 
 badly, but the fluid is not rendered sterile. By means of a simple 
 apparatus invented by Dr. Gozard, I learned that repeated shocks 
 in nowise affect the life of microbes. The microbes experimented 
 upon — staphylococcus aureus, colon bacillus, streptococcus of ery- 
 sipelas, sporulating or non-sporulating bacillus anthracis — were in no 
 way affected by the mechanical action. 
 
 Action of High Pressures. The influence of pressure has been 
 studied by various experimenters. The somewhat dissimilar results 
 are referable to the diversity of the methods employed. The experi- 
 ments of Regnard, Dubois, Certes, and Cochin demonstrated that 
 
GENERAL CHARACTERS OF PATHOGENIC BACTERIA. 
 
 low beings resist very high pressure. The beer yea I i capable of 
 bearing 300 to loo atmospheres for several days without being &b- 
 stroyed. When submitted to L000 atmospheres lor one, hour it 
 becomes torpid and, an hour later, ii is again capable of producing 
 fermentation of sugar. The same is true of algae and infusoria which 
 have been subjected to a pressure of 600 atmospheres. The algae 
 germinate only after a week; the protozoa remain for some time 
 motionless and then resume their movements, llegnard further 
 learned that relatively higher organisms such as mollusks, crustac 
 and leeches can endure 500 or 000 atmospheres without, perishing. 
 
 As to bacteria, the effects of pressure vary considerably, according 
 to experimental conditions. In fact, it seems demonstrated that 
 compressed gases exert a very noxious influence upon several mi- 
 crobic species. According to P. Bert, oxygen, under a pressure of 
 from 8 to 10 atmospheres, arrests putrefaction. The atmospheric 
 air, under the same conditions, produces an analogous but less intense 
 effect. In studying the bacillus anthracis, Prof. Chauveau showed 
 that oxygen at 12 atmospheres weakens the vitality of this microbe 
 and at the same time diminishes its virulence to such an extent as 
 to transform it into a vaccine. Carbonic acid under pressure is 
 equally harmful to bacteria. C. Fraenkel recognized that seltzer 
 water contains no microbes. All species do not, of course, possess 
 the same power of resistance. Hence the apparently contradictory 
 results obtained by Sabrazes and Bazin. 
 
 . The effect of 800 or 1000 atmospheres upon the four microbes 
 (experimented upon in the author's first researches 1 ) proving nega- 
 tive, the author thought it important to study the action of still 
 greater pressures. He experimented with an apparatus by means of 
 which the pressure could be raised to 2903 atmospheres, the cultures, 
 as usual, being enclosed in rubber tubes. Since, however, the high 
 pressure caused the water to filter through the walls of the apparatus, 
 the author filled the cylinder, in which the tubes were placed, with 
 oil. A special contrivance, set in motion by means of a motor engine, 
 raises the pressure gradually, so that it takes ten minutes to attain 
 2903 atmospheres. This pressure, the highest that can actually be 
 obtained, is kept up for two minutes: it is not possible to further 
 prolong the experiment without danger to the apparatus. The 
 pressure is then allowed to fall to the normal: this descent is rapid, 
 
 1 Roger. Action of High Pressures upon Some Bacteria. Comp. Rend, de lAcademie 
 des Sciences, Dec. 3, 1S94; Arch, de phys.. Jan. 1. 1S95. 
 
52 ISFECTIOUS DISEASES. 
 
 as it lasts but ten seconds. The latter fact is of considerable impor- 
 tance, for perhaps some of the effects obtained may be due to de- 
 compression. 
 
 Under these conditions the colon bacillus and staphylococcus 
 aureus have hitherto suffered no modification; their cultures were 
 as luxuriant after as before the experiment. Their functions were 
 not even disturbed, since the staphylococcus preserved its chromo- 
 genic power. 
 
 The streptococcus was sown in agar-agar before and after com- 
 pression. The tubes were placed in the incubator at 6 p.m. and 
 examined at 9 a.m. the following day. Those which had received 
 the normal cultures were covered with colonies; the others showed 
 no growth. In the evening, however, they presented colonies one- 
 third less numerous than the control tubes. Apart from these 
 numerical differences, which remained the same the following days, 
 there was no appreciable modification either in the appearance of 
 the colonies or in the form of the microbes. 
 
 In conjunction with the culture experiments inoculations were 
 practised upon rabbits. Ten drops of the culture were introduced 
 under the skin of the ear. Two days after the rabbits which had 
 received the streptococcus subjected to compression were attacked 
 by erysipelas of the ear. The affection grew worse on the following 
 days, then began to subside, and disappeared on the tenth or 
 eleventh day. The controls presented no local lesion; they suc- 
 cumbed to a general infection five or six clays after the inoculation.. 
 
 A pressure of 2903 atmospheres (about 3000 kilogrammes per 
 square centimetre) is, therefore, capable of killing a few streptococci. 
 It induces in those which survive a sort of torpidity as expressed by 
 a notable delay in development, and, what is of greater consequence, 
 it diminishes their virulence to such an extent as to leave them the 
 power to produce only a local and rapidly curable lesion. 
 
 The effects of pressure upon the bacillus anthracis are analogous 
 to the above. 
 
 It may, however, be questioned whether the effects observed with 
 the streptococcus and the bacillus anthracis are due to the increase 
 of pressure. The rise of temperature caused by compression of the 
 fluids may, perhaps, account for all these phenomena. Commandant 
 Meillet, who has studied this problem, calculated that under a press- 
 ure of 2903 atmospheres (3000 kilogrammes) the rise of temperature 
 was only 9.54° F. (5.3° C). This is rather too high a figure, as it 
 
GENERAL CHARACTERS OF PATHOGENIC BACTERIA 
 
 assumes that all the force is transformed into heat. The thermal 
 effect cannot, therefore, explain the action of pre sure. 
 
 In order, however, to influence the life or function* of microbe 
 enormous pressures far in excess of actual cosmic variations musl 
 be employed, since the pressure at the bottom of the sea i far less 
 (500 or 600 kilogrammes). Consequently, if may I"- Btated thai 
 changes of atmospheric pressure occurring on our globe play no r61e 
 in the modification of the virulence of the microbes surrounding u . 
 
 Action of Physical Agents on Bacteria. V i well known. 
 physical agents, especially heat and light, exerl a harmful influence 
 upon bacteria. 
 
 Action of Heat. Heat is daily employed for purposes of steriliza- 
 tion. All bacteria, however, are not destroyed at the same tempera- 
 ture. There are some that can live, develop, and multiply between 
 158° and 165° F. (70° and 74° C). Globig found in the soil thirty 
 species living between 122° and 158° F. (50° and 70° C). Miquel, 
 Olivier, Rabinowitsch, and Macfayden studied the thermophilic 
 microbes found in hot spring waters and notably in sulphurous 
 waters. 
 
 For the same bacterial species, sensitiveness to heat varies accord- 
 ing to several conditions. The spores are more resistant than the 
 adult forms. Heat is more destructive to the microbes when the 
 latter are contained in a fluid medium than when in a desiccated 
 state. Finally, the action of heat is considerably increased by 
 the presence of air which produces oxidation unfavorable to bac- 
 teria. 
 
 Immersed in water at 140° F. (60° C.) the tubercle bacillus lives 
 for twenty minutes; and in water at 158° F. (70° C), for ten minutes. 
 Boiling water at 212° F. (100° C.) kills it in five minutes. The 
 same bacillus is capable of resisting a dry heat of 212° F. for several 
 hours. 
 
 The influence of air is shown by Dr. Roux's experiments. When 
 subjected to the combined action of air and a temperature of 15S° F. 
 (70° C.) the spores of bacillus anthrads die in sixty hours: when 
 protected from air they live one hundred and sixty-five hours. 
 
 Resistance to cold is far more considerable. Ice contains numerous 
 microbes. Dr. Pictet subjected bacteria to temperatures of — 166° F. 
 (—110° C.) and even —328° F. (—200° C.) without being able to 
 kill them. Prof. D'Arsonval immersed some in liquefied air with- 
 out causing them to lose their power to vegetate. 
 
54 ISFECTIOUS DISEASES. 
 
 Action of Light. The influence of sunlight is at least as important 
 as that of heat. It may easily be proved by the following experi- 
 ment: A few drops of an anthrax culture are spread upon a gelatin 
 plate, which is then covered with a glass upon which pieces of black 
 paper are pasted. When exposed to light, development takes place 
 in the protected parts, and the bacteria exactly reproduce the designs 
 figured by the pieces of black paper. 
 
 This influence of sunlight is constantly at work in nature. Bacteria 
 are speedily destroyed at the surface of the soil, while at twenty 
 inches below the surface they find excellent conditions of resistance, 
 and may retain their vitality for more than five months. 
 
 The results are similar for bacteria immersed in water. 
 
 Pansini introduced a few drops of an asporogenic anthrax culture 
 into water which he then subjected to the action of the sun. The 
 number of bacteria was primarily 2520 per cubic centimetre. At 
 the end of twenty minutes the number was reduced to 130, and at 
 the end of half an hour to 44 per cubic centimetre. After forty-five 
 minutes there were none to be found. 
 
 Procaccini took sewer water containing 300,000 to 420,000 bac- 
 teria per cubic centimetre and subjected it to solar influence. At 
 the end of the day the water was sterile. 
 
 The following is another experiment made under perfect condi- 
 tions: The water of the Isar, before its entrance into the city of 
 Munich, was examined by Buchner at different hours of the day. 
 The highest figure was found at 4 a.m., as bacteria had increased 
 during the night, and their number then reached 520 per cubic cen- 
 timetre. The minimum was observed at 8 p.m. Exposed to the sun 
 all day, the water contained no more than five bacteria per cubic 
 centimetre. 
 
 The experiments of Marshall Ward tend to prove that light acts 
 directly upon the anthrax spores, and that its action is inhibited 
 when the plant is protected by means of a screen intercepting the 
 blue and violet rays. Thus, as Downes, Blunt, Arloing, Buchner, 
 and Frankland had already seen, it is the most refrangible rays which 
 possess germicidal power. The orange and red rays do not disturb 
 the development of bacteria. 
 
 As in the case of heat, the action of light is favored by the presence 
 of air. Dr. Momont demonstrated that anthrax spores perish after 
 forty-eight hours of insolation when they are in contact with air. 
 In vacuo they live for one hundred and ten hours. 
 
GENERAL CHARACTERS OF PATHOGENIC BACTERIA 
 
 Light modifies the functions of bacteria at the ame time that it 
 affects their vitality. Anthrax is attenuated under it influence. The 
 red bacillus of Kiel ceases fco produce pigment, at times permanently, 
 so that if it is sown in the shade, it does not recover its chromogenic 
 function. 
 
 The study of the other physical agents a this connection 
 matter of considerable difficulty. Hence, in the old experiment* 
 upon the effects of electricity the currents employed produced heat 
 and electrolysis. The germicidal action was due, therefore, to ther- 
 mal or chemical modifications. Those experimenters who have taken 
 cognizance of these sources of error have not been able to detect any 
 direct action of electricity upon bacteria. 
 
 Action of Chemical Agents. Those chemical agents which are 
 capable of unfavorably affecting bacteria are called antiseptic agents. 
 Among gases there is, for instance, ozone, of which, as is known, 
 great quantities are often found in the atmosphere. Its action is 
 very energetic, at least upon the adult forms. The asporogenic 
 anthrax bacillus is killed under its influence in five hours, but the 
 spores perish only after three or four days. 
 
 The antiseptics properly so called possess the very curious property 
 of stimulating the functions of bacteria when employed in minute 
 quantities. Under their influence the chromogenic microbes produce 
 a greater amount of pigment. When the amount of the antiseptic 
 is raised the chromogenic power declines and even disappears. 
 Vegetation then becomes slow, is arrested, and finally the microbe 
 perishes. 
 
 Carbolic acid is one of those most frequently employed. In solu- 
 tions of 1 per cent, it kills the asporogenic anthrax bacillus in ten 
 seconds. If the microbe is spore-bearing, life persists for thirty-seven 
 days in a solution five times stronger. 
 
 In order to promote the action of antiseptics, it is advisable to 
 raise the temperature of the medium. Here is a fact of consider- 
 able importance from a practical point of view. For purposes of 
 disinfection, warm solutions should be used. Thus, while anthrax 
 spores resist a 5 per cent, solution of carbolic acid at ordinary 
 temperature, they perish in the same solution in two hours if the 
 temperature reaches 131° F. (55° C), and in three minutes if it rises 
 to 134.6° F. (57° C). 
 
56 I SFECTIOUS DISEASES. 
 
 Determination of Pathogenic Species. 
 
 In order for a microbe to be considered as the true cause of a dis- 
 ease it must.. it is said, fulfil the following four conditions: it must 
 be present in all individuals suffering from the disease; it must not 
 be found in other diseases; it must be possible to isolate and cultivate 
 it : and, finally, it must reproduce the disease by inoculation of its 
 cultures. 
 
 These rules are excellent, but cannot be accepted as absolutely 
 exact, and they therefore require some discussion. 
 
 The first precept is, perhaps, the most immutable, and would seem 
 to admit of no exception. In certain cases, however, the search for 
 microbes may be fruitless without impairing the value of previous 
 positive findings. The pathogenic agent is not necessarily dissem- 
 inated throughout the organism. It is, therefore, possible to over- 
 look it if cultures are not prepared from every tissue and fluid. Even 
 in those cases in which numerous cultures are made the result may 
 be negative for the reason that the pathogenic agent is destroyed 
 before the time of examination, having left lesions or a special 
 cachexia. Suppurations originated by microbes persist long after the 
 extinction of the microbes. Analogous facts are matters of daily 
 observation in experimental pathology. We inoculate a mild virus, 
 the animal dies after a considerable length of time. At that moment 
 the most minute examination, the most exhaustive series of cultures 
 fail to reveal the microbe introduced. It has perished, but the post- 
 infectious events have followed their course to a fatal termination. 
 
 Another cause of error results from the fact that the principal 
 microbe may be accompanied by, and even be lost among, other 
 microbes. Necropsy is generally practised too late to give reliable 
 results, for during the agony various species of microbes, particularly 
 the colon bacillus, pass from the intestine into the viscera, fluids, and 
 tissues, and it is these microbes wdiich are found at the necropsy. 
 These germs develop in artificial media more readily than the specific 
 microbes, and if they are of the pathogenic class, as is the colon 
 bacillus, they may readily be mistaken for the cause of infection. 
 
 Even when examination is made during life microbic associations 
 are apt to lead to error. In diphtheria, for instance, it is quite 
 exceptional to meet with a case free from such associations. It is 
 not strictly correct to speak of pure diphtheria. Those cases in which 
 inoculation into serum gives rise, at the end of fifteen hours, to no 
 
GENERAL CHARACTERS OF PATHOGENIC BAOTERl I 
 
 other than the colonies of Loeffier's bacilhu arethu de ignated. If, 
 however, the same culture is examined after a fein da} . a greal 
 number of other microbes are found. In certain instance "i true 
 diphtheria I he specific microbe may be absent , having been di 
 
 by common bacteria. 
 
 Analogous statements may be made with reference to cutanea 
 diseases. Secondary infections play a very greal r61e in all affections 
 of the skin and in eruptive fevers. For instance, al a certain period, 
 pustules of variola always contain a greal number of microbes which 
 have nothing to do with the cause of the disease. These common 
 bacteria, may at limes even penetrate into the organism and consid- 
 erably embarrass bacteriological study. 
 
 There are other clinical types in which microbic association is still 
 more important, not to say indispensable. Such is the case in tet- 
 anus. The bacillus of Nicolaier is incapable of developing in healthy 
 tissues. In order to be able to act, it requires the assistance of 
 auxiliaries to reduce the resistance of the animal organism. The 
 morbid focus, therefore, contains various microbes, but the tetanus 
 bacillus alone secretes the poisons which reproduce in animals the 
 characteristic phenomena of the disease. 
 
 Finally, in certain cases, the morbid centre contains several bac- 
 teria endowed with wellnigh similar properties. In such instances 
 the doubt as to the respective share of each of them is unavoidable 
 and legitimate. 
 
 The third law which has been cited will not detain us long. It is 
 now recognized as a common truth that the relations existing between 
 pathogenic agents and diseases are not such as they have been 
 defined. It is scarcely necessary to recall that the streptococcus 
 sometimes produces erysipelas, sometimes phlegmons, sometimes 
 general infections, septicemias, and pyemias. In the beginning of 
 bacteriological study facts of this kind seemed inadmissible. We 
 were so used to our nosographic groupings that we hesitated to 
 disturb them by etiological researches. The day is long past, how- 
 ever, when a constant relationship between disease and microbe was 
 obstinately maintained. It is now admitted by all that one and the 
 same microbe may give rise to most varied maladies. In order, how- 
 ever, to justly consider an animate agent as the cause of an affection, 
 it is necessary to isolate, cultivate, and inoculate it. Here other 
 difficulties are encountered. Certain beings visible under the micro- 
 scope do not develop outside the organism and are not pathogenic 
 
58 INFECTIOUS DISEASES. 
 
 for animals. To cite the best-known example, such is the parasite 
 of malaria. It is easy to understand, therefore, why Laveran's 
 discovery was not readily accepted. Ten years of ardent discussion 
 was necessary to convince the opponents. 
 
 Inoculation of the pathogenic agent — viz., the reproduction of the 
 observed disease in animals — has led to such encouraging results, 
 and its methods are so simple that it is resorted to on every hand. 
 
 The progress of experimental pathology has been most wonderful, 
 but science is unfortunately overrun with uncertain and erroneous 
 data, for which hasty and incomplete contributions are responsible. 
 Moreover, owing to a natural tendency of the human mind, experi- 
 menters have asked of the laboratory more than it could give. Not 
 contented with the information which it is capable of furnishing with 
 regard to etiology, they wished to find certain and accurate indica- 
 tions concerning diagnosis, prognosis, and treatment. If, in certain 
 instances, experimentation has responded to all that was asked of 
 it, it has more frequently yielded uncertain and misleading results 
 The fact is that there is no constant relation between the virulence 
 of pathogenic agents for man and their action upon animals. Experi- 
 mentation demonstrates this. A microbe exhalted for one species 
 may be attenuated for another. While highly virulent for man, it 
 may be harmless for laboratory animals. 
 
 Even when the virulence of a microbe undergoes no variation its 
 effect may vary greatly, according to the previous state of the in- 
 vaded organism. It is a matter of frequent occurrence that patients 
 gravely infected transmit a mild infection, and vice versa. The his- 
 tory of variola offers numerous illustrations of this fact. Likewise, 
 two individuals contract a venereal disease on contact with the same 
 woman — i. e., under conditions as identical as possible. In one of 
 the cases, however, the infection is benign; in the other it pursues 
 an alarming course. 
 
 These remarks are by no means intended to diminish the impor- 
 tance, but to indicate the difficulties of experimental researches. We 
 shall endeavor to lay down rules which should guide bacteriological 
 experimentation . 
 
 Role of Experimentation in the Study of Infectious Diseases. 
 A first difficulty is the choice of the animal. The mouse, the guinea- 
 pig, and the rabbit are the animals most frequently experimented 
 upon; much less frequently the dog and the monkey are employed. 
 Larger animals are difficult to manage and also too expensive. What, 
 
GENERAL CHARACTERS OF PATHOGENIC B ICTER1 I 
 
 however, complicates the problem] is the fad thai some di i 
 exclusively human. Syphilis is of this number. In such ca ee the 
 demonstration of the pathogenic agenl become a matter of seriouc 
 difficulty, as the unquestionable and final proof i lacking. I be same 
 remarks are applicable to other infections peculiar to man, such at 
 mumps, typhus fever, and leprosy. 
 
 The impossibility of transmitting certain diseases t<> animal 
 compelled some authors to operate upon man. Long before the 
 period of bacteriology attempts of this character wen- made, and 
 science undoubtedly benefited by the inoculations of syphilitic virus. 
 
 Although not many years have elapsed since thai period, a higher 
 and more just conception of our duty toward patients intrusted to 
 
 our care has caused us rightly to condemn these eriininal attempts. 
 At the present day nobody would venture to inoculate the virus of 
 syphilis, variola, or cancer. Should the subject consenl to submit 
 to such experiments, it would be our duty to refuse If, however, 
 an investigator believes he has discovered the pathogenic agent of 
 some infection, he has the right to experiment upon himself. 
 
 When a microbe is inoculated into an animal, three results are 
 possible: (1) the animal may be endowed with natural immunity and 
 resist in spite of all efforts of the experimenter; (2) it may contract 
 a disease altogether similar to that from which the microbe under 
 study is derived — in which case, the result is perfect and convincing ; 
 (3) finally, it may present morbid symptoms which seem to have no 
 analogy with those observed in man. In the latter instance the 
 experimenter remains in doubt. 
 
 The last result may be illustrated by numerous examples. The 
 pneumococcus, for instance, produces fibrinous pneumonia in man. 
 The microbe is obtained from the exudate, cultivated, and then 
 inoculated into a rabbit or a mouse, which dies in twenty-four or 
 forty-eight hours without presenting any pulmonary lesion. It has 
 succumbed to a genuine septicemia. 
 
 The result is evidently somewhat discouraging. It must, however, 
 stimulate the experimenter to persist in his researches, for by chang- 
 ing the animals, by modifying the channel of introduction of the 
 pathogenic agent, by producing various concomitant lesions, or by 
 changing the culture medium, he may often obtain more conclusive 
 results. Let us, therefore, lay down the principal rules of experi- 
 mentation. 
 
 Inoculations are at times practised with virulent material taken 
 
60 INFECT 10 1 'S D IS E. I N i'.s. 
 
 directly from a diseased individual. This method of procedure is 
 now abandoned and is hardly ever resorted to since the introduction 
 of cultures. It may, nevertheless, be of service in those instances 
 in which the pathogenic agent is unknown. In hydrophobia, for 
 example, direct inoculations only are made, and by means of certain 
 procedures the virus is modified and graduated as easily as if it had 
 been isolated and cultivated. 
 
 In some cases, even when it is possible to cultivate the microbe, 
 it may be preferable to make inoculations with the diseased tissues, 
 for, while the passage through artificial media modifies the virulence, 
 it generally weakens it, and sometimes imparts to it particular char- 
 acters. Inoculations in series are equally useful for strengthening a 
 virus and for determining the virulence of a microbe in the organ- 
 ism. The last consideration guided me in my researches on avian 
 tuberculosis. With Drs. Cadiot and Gilbert, the author inoculated 
 directly into mammalia tuberculous products derived from birds, and, 
 reciprocally, tuberculous products of mammalia were inoculated into 
 birds. We were thus able to determine the real virulence of the 
 bacillus. The results proved that we were right in so acting, since 
 the employment of cultures gives rise to errors of interpretation. 
 
 In the majority of cases inoculations are made with pure cultures. 
 This method alone furnishes reliable indications as to the nature of 
 the pathogenic agents. It alone enables us to differentiate the mi- 
 crobes, to interpret their biological characters, and to modify their 
 power and action upon the organism. The variations, however, 
 which occur are not always due to the intervention of the experi- 
 menter. The virulence of a culture is sometimes lessened or van- 
 ishes for some unknown reason. This inconvenience has recently 
 been remedied by modifying the culture media and by abandoning 
 more and more the employment of bouillons. Animal fluids, serum, 
 ascitic fluid, pleuretic effusion, clefibrinated blood are made use of 
 instead. These are sometimes mixed with bouillon or agar-agar, or 
 the cultures are prepared within the living organism itself. Small 
 capsules of collodion containing the microbe are introduced into the 
 abdominal cavity. Diffusion of the organic fluids readily takes place 
 through the membrane, which protects the pathogenic agent against 
 the phagocytes. 
 
 Even under these conditions, however, the cultures do not always 
 preserve their virulence or their uniformity. Just as with the higher 
 organisms, which, when placed under apparently identical conditions, 
 
GENERAL CHARACTERS OF PATHOGENIC BACTERIA v,\ 
 
 are always dissimilar, the microbes contained in 8 medium are not 
 all endowed \\ i i h the same degree of vitality. Among t he individuals 
 swarming in a culture capsule some are more active or more pathogenic 
 than others. 11 is very difficult, not to say impossible, to obtain 
 perfectly uniform cultures. There is, however, much of inti 
 in making attempts in this direction, since this individual vari- 
 ability of pathogenic elements is I lie cause of many eontradic 
 results. 
 
 Determinism in Bacteriology. II is curious to note how little 
 determinism in bacteriology is regarded. The reason is, perhaps, 
 that determinism in this branch of research presents particular diffi- 
 culties. To declare, however, that a bacterium inoculated into sim- 
 ilar animals and under apparently identical conditions produces 
 different effects is an avowal of impotence. That such diould be 
 the case with regard to man cannot be avoided. We must submit, 
 so to say, to the caprices of clinical phenomena. We are victim- of 
 the chances and accidents of observation. In experimental | eth- 
 ology, however, we must endeavor to suppress the unforeseen and the 
 inconstant. We must seek to obtain fixed and invariable results. 
 This is, of course, a matter of great difficulty, for, while it is difficult 
 to determine the phenomena, even in physiological experiments, the 
 problem is far more complex in bacteriology. Here we combine two 
 essentially variable factors. The animals, in spite of appearances, 
 possess individual differences. On the other hand, the microbe, as 
 a living being, possesses no immutable, well-defined properties such 
 as are peculiar to a crystallized chemical poison. The result is that 
 a microbe of variable action is introduced into an animal of variable 
 reactions. The causes of uncertainty are thus added. "While it is 
 possible to interpret certain problems and to determine certain phe- 
 nomena, in most cases this means to displace the unknown. For 
 instance, let us follow the passage of the bacillus anthracis through 
 the placenta. A certain number of pregnant guinea-pigs are inocu- 
 lated; at the necropsy it is found that in some of the animals the 
 bacillus has invaded the foetus, but not in all. Such is the fact. 
 Dr. Malvoz determined this by showing that the placenta does not 
 permit the passage of organisms except when it is altered. If it 
 remains intact, it acts as a perfect filter. Consequently, we are able 
 to state precisely that the bacillus traverses the diseased placenta, 
 but it does not pass through the intact placenta. It is evident, 
 however, that the problem is only modified. In explaining a first 
 
62 IXFECTIO US DISEASES. 
 
 point a new one is introduced. It remains to determine the causes 
 which permit or prevent localization of the bacillus in the placenta. 
 When we become acquainted with them the phenomenon will then 
 be elucidated. 
 
 The aim of the experimenter is, therefore, to reproduce in animals 
 constant alterations and identical modifications. Next, he must 
 vary one of the experimental conditions to obtain new effects. He 
 will then be master of the phenomenon and be in a position to 
 draw conclusions concerning the mechanism of infectious occur- 
 rences. 
 
 Through this procedure it has already been possible to solve cer- 
 tain questions in etiology and pathogenesis. This has been accom- 
 plished by modifying the local or general resistance of the animals 
 by various means, such as intoxication, overwork, fasting, section of 
 nerves, ligature of arteries, traumatism of tissues, etc. Morbid dis- 
 positions are created thus, and the results obtained lead to a better 
 understanding of the mechanism of the pathological events. 
 
 This is not sufficient, however. A more profound study of the 
 lesions is required. It is of the highest interest to note that not 
 every part of a diseased organ is affected in the same measure. Along 
 with diseased cells are found others in a perfectly healthy condition. 
 Thus, after particularization of the species, of the race, and of the 
 individual, particularization of the organs and tissues, and, pursuing 
 the analysis still further, even particularization of the cells has been 
 admitted. This fact, which is not without interest from a philo- 
 sophical point of view, is the outcome of pathological studies. Normal 
 anatomy and physiology could not lead us to this conclusion. On 
 section of a normal organ or tissue all the cells seem alike. It is 
 evident, however, that if they were all alike they should present the 
 same alterations under the influence of the same pathogenic cause. 
 It is difficult to explain why two neighboring cells placed apparently 
 under identical conditions are differently affected. The age of cells 
 may be responsible. These elements, according to the universal law 
 governing all living organisms, succumb and are renewed unceas- 
 ingly. Hence, it is impossible to determine whether two cells close 
 to each other are not of very different ages. It is, then, readily 
 conceivable that their resistance should vary considerably according 
 to their ages. It must also vary in proportion to their functional 
 activity, since it seems to be certain that particular parts of a gland 
 rest while other parts are at work. If, therefore, for any of the 
 
GENERAL CHARACTERS OF PATHOGENIC BACTERIA, 63 
 
 reasons above indicated certain cells are more affected than others, 
 their descendants will differ from otheri Ln their morbid aptitude) 
 
 or immunities. 
 These considerations will find numerou applications in the 
 
 of pathological anatomy and physiology. They will furni h u with 
 a key to cellular lesions. 
 
CHAPTER III. 
 
 ETIOLOGY OF INFECTIONS. 
 
 Division of Infections, According to Their Origin, into Heteroinfections and Autoinfec- 
 tions. Transmission by Direct Contact. Transmission through Air, Water, and 
 Soil. Role of the Invertebrates. Transmission through Objects and Clothing. 
 Disinfection of Apartments, Effects, Conveyances. Transmission by Plants. 
 Transmission by Food. Autoinfections. Distribution of Microbes in the Normal 
 Organism. Importance of Auxiliary Causes in the Development of Infections. 
 Influence of Regions, Climates, Seasons. Influence of Race, Age, Sex. Role of 
 Heredity and Innateness. Action of External Agents. Role of Poisons. Role of 
 Fasting and of Fatigue. Development of Epidemics; Their Modification through 
 Time and Space. 
 
 Heterointoxications and Autointoxications. 
 
 Infectious diseases may be clue to two different origins: on the 
 one hand, the pathogenic germs come from without, and their intro- 
 duction into the organism is the evident cause of the morbid process ; 
 in other instances they are already present within the organism as 
 simple epiphytes giving rise to no disturbance, but always ready to 
 manifest their virulence on the slightest occasional cause. These 
 divisions are indicated by the terms heteroinfection and autoinfection. 
 
 The recognition of autoinfections is of recent date and accounts 
 for the numerous facts which were formerly ascribed to morbid spon- 
 taneousness. As soon as the microbes resume their pathogenic ac- 
 tivity, however, they are capable of invading healthy persons and 
 exerting their noxious power: the disease, born spontaneously, thus 
 becomes transmissible. 
 
 A disease is said to be contagious when it can be communicated, 
 either directly or indirectly, by a diseased individual to a healthy 
 one. Although, in the majority of cases infecting and infected indi- 
 viduals belong to the same species, this is not always the case — man 
 may be contaminated by animals. 
 
 In the case of direct transmission, contagion occurs in two different 
 ways: either by contact or by inoculation. In the former instance 
 the morbid germs derived from the infected subject invade the 
 healthy organism through unbroken mucous membranes, generally 
 through the respiratory passages or the alimentary canal. In the 
 
ETIOLOGY OF INFECTIONS. 
 
 latter case the vims is deposited, nol upon the surface, but in the 
 interior of the economy i. <•., in a wound or abra ion. 'I he di 
 is then said bo be inoculated. H musl be noted, however, thai i 
 contagious disease is inoculable, but thai the reverse i uol true. 
 
 Recent epidemiological researches tend considerably to limit the 
 r61e played by air. They show that transportation i . a a rule, 
 effected l>y persons imd objects. Of the latter the besl known are 
 the utensils employed at meals, such as forks, spoon-, and gla 
 those used for the toilet, such as brushes, combs, and sponges. Cloth- 
 ing, bedding, books, letters, and coins find paper money mufll also 
 be mentioned. Finally, in many cases in which propagation by air 
 seemed to be demonstrated, if is now recognized that, in reality, 
 transmission occurs through the agency of certain insects which in- 
 gest the microbes and then deposit them beneath the skin by true 
 inoculation. Such is notably the case in malaria. 
 
 When ejected from the diseased organism, certain germs rapidly 
 -die; others often survive for a long time in water and soil, upon 
 floors, walls, etc. We must, therefore, study these diverse origins 
 -of infections in their order. 
 
 Transmission of Infections by Contact. Let us first consider 
 the simplest case — i. e., transmission by immediate contact of healthy 
 with diseased individuals. Here is an example of genuine inoculation 
 which sometimes requires a previous erosion of tissues. At other 
 times inoculation is effected through the intact epithelia, as occurs 
 in venereal diseases: gonorrhea, soft chancre, and syphilis. Such 
 immediate contact is not, of course, indispensable, since the virus 
 may be deposited upon objects which serve for its transmission. 
 The characteristic feature of this group is the fact that the patho- 
 genic agents manifest little if any tendency to diffusion. They are 
 not propagated by air or water and they do not vegetate outside the 
 organism. It has been said that the gonorrheal virus embodied in 
 pus particles may be spread by air, and in this maimer epidemics 
 of purulent ophthalmia invading a hospital ward are sometimes 
 explained. It must be remembered, however, that, in most cases, 
 minute inquiry demonstrates that propagation is due to immediate 
 contact. The same is true of vulvovaginitis in children : the microbe 
 is conveyed by the mother's contaminated hands, toilet articles, and 
 particularly by sponges. Anthrax, glanders, and at times tubercu- 
 losis and actinomycosis may also be directly transmitted by acci- 
 dental inoculation. The same should be true of hydrophobia. 
 
Q Q INFE OTIOUS DISEA SES. 
 
 although, in this regard, there is as yet no convincing observation. 
 Bites by hydrophobic individuals have thus far never given rise to 
 the disease. 
 
 In a second group may be classed those infectious germs which 
 are capable of transmission to a distance through the agency of 
 squama 1 , urine, expectoration, etc. The cutaneous squama? are 
 often considered the agents of transmission of the eruptive fevers 
 and erysipelas. For the latter disease, however, the mechanism of 
 transmission is scarcely acceptable, since bacteriological researches 
 demonstrate that the products of desquamation contain no strepto- 
 cocci. 
 
 The transmissibility of eruptive fevers varies according to the 
 infection considered. 
 
 The germ of measles is contained in the oculonasal secretions and 
 saliva, as was demonstrated by the successful inoculations made by 
 Monro and Looke in the eighteenth century, and by Mayo in 1860. 
 In accordance with these experiments, observation teaches us that 
 measles is contagious before the stage of eruption, and soon ceases 
 to be so, since five or six days after the appearance of the exanthem 
 the germ seems to be destroyed. In very rare exceptions convales- 
 cents from measles have been known to infect healthy persons fifteen 
 and even thirty days after the beginning of the disease. 
 
 The squamae are generally believed to be the media for the trans- 
 mission of the germs of scarlatina. According to recent researches 
 by Dr. Lemoine, however, the morbid germs are found in the secre- 
 tions of the throat, and the disease may thus be transmitted before 
 the appearance of the eruption. By questioning scarlatinal patients 
 I have found in several cases that the typical disease had developed 
 in consequence of contact with an individual suffering merely from 
 a sore throat. 
 
 As in measles, the germ of scarlatina is found in the throat and 
 not in the squama?. The latter may become the media of transmis- 
 sion in so far as they are apt to be contaminated by the saliva of 
 the patient. It is also to be remembered that the virus of scarlatina 
 is more persistent than that of measles. The period of forty days, 
 fixed by the Council of Hygiene (of Paris), is generally sufficient, 
 though contamination has exceptionally taken place after the expi- 
 ration of this time. Unlike the scarlatina germ, that of measles 
 possesses but slight viability and diffusibility. Two or three hours 
 outside of the diseased organism is sufficient to destroy the virus. 
 
ETIOLOGY OF INFECTIONS. <;7 
 
 Epidemiology of Smallpox. The study of smallpox strikingly 
 illustrates the mode of propagation of epidemics of thi di ei 
 
 The microbe of smallpox, by its greal resistance, seem to clo 
 resemble that of scarlatina, bul it is far less diffusible. I' 
 mission through air has not been demonstrated. In man} 
 which this mode of propagation was assumed inquiry established 
 that a patient or some attendant bad, in violation of instructions, 
 trespassed the boundaries of isolation, or that disinfection ol con- 
 taminated objects had not been thorough. 
 
 During the epidemic which raged in 1900 we received 928 patient* 
 in the Hospital d'Aubcrvilliers. Of this number, 246 had been con- 
 taminated directly by contact with individuals suffering from variola. 
 We have established a rule that a smallpox patient must remain in 
 the hospital for at least forty days. Those who need a certificate 
 for resuming their work respect the rule, but others, under various 
 pretences, leave the hospital too soon and spread the disease. The 
 study of the epidemic of 1900 further shows that the poorer sec- 
 tions of Paris suffered most, since the rules of hygiene are not well 
 observed by the inhabitants of these quarters. When there is a 
 patient in a workman's family the neighbors often come to nurse the 
 sick, and then return home or to work without taking any precau- 
 tions. In one of my observations the janitress nursed a poor indi- 
 vidual attacked by smallpox, and the devotion of this brave woman 
 resulted in the transmission of the malady to the majority of the 
 tenants. 
 
 The mildest cases are particularly dangerous for the public. An 
 individual is seized with malaise, muscular pain, fever, and at times 
 with rachialgia. He stays at home for three or four days. An 
 eruption then makes its appearance: a dozen large papules resem- 
 bling acne appear upon his face. At this time the patient feels well, 
 and resumes his occupation. Not having consulted a physician, he 
 is ignorant of the nature of the disease. It must also be remembered 
 that many physicians are unable to diagnose variola since epidemics 
 have become rare. Nevertheless, the failure of a physician to recog- 
 nize smallpox has often been the cause of its propagation. 
 
 Epidemics in General. It seems that the study of conditions 
 governing the development of epidemics in general tends more and 
 more to reduce the role of transmission at a distance and to empha- 
 size the importance of direct contamination. The latter mode is 
 most often responsible for the infection of wounds. Though trans- 
 
68 IXFECTIO US DISEASES. 
 
 mission by air is possible, propagation is, in the majority of cases, 
 effected through insufficiently cleansed instruments and hands. 
 
 Some twenty years ago, when infection of wounds was still fre- 
 quent, I had the opportunity to observe an epidemic of erysipelas 
 in a surgical ward. The first case was seen one morning. The 
 following day a second case occurred, and others appeared on sub- 
 sequent days. Transmission by air and the infection of the ward 
 was assumed. On studying the course of the epidemic, however, it 
 was noticed that only those patients had been attacked at whose 
 bedsides the attendant surgeon and his assistants had stopped. The 
 latter had received the germ of erysipelas from the first patient and 
 conveyed it to the others. Those patients who had not been visited 
 remained exempt. Here, then, is a series of facts contrary to the 
 theory of the distribution of contagium through the air. 
 
 Infection may also be contracted by contact with diseased animals. 
 In certain instances the virus is deposited directly in a wound; at 
 other times by means of a bite, as in the case of hydrophobia ; or by 
 accident in handling diseased animals or cadavers. It has been 
 asserted that scarlet fever is an infection of bovine origin and that 
 it may be propagated by milk (Klein). Some authorities believe 
 that all the eruptive fevers are of animal origin. Finally, an infec- 
 tion of parrots, which has recently been studied and is due to a 
 bacillus related to the colon bacillus, is highly virulent for man. 
 This infection is known as psittacosis. 
 
 Transmission of Tuberculosis by Contact. Of all infections 
 tuberculosis is incontestably the most readily transmitted among 
 different beings. Direct contamination of the healthy man by dis- 
 eased animals is no longer a matter of doubt since the unity of 
 tuberculosis in all animals has been admitted. While there are sev- 
 eral varieties of Koch's bacillus the differences separating them are 
 not of sufficient dignity to constitute specific characters. From a 
 scientific standpoint, it is generally admitted that the digestive 
 organs may be infected by ingestion of the flesh or milk of tuber- 
 culous animals. The frequency of such cases has not, however, been 
 established. 
 
 Direct inoculation of tuberculosis seldom takes place. Several 
 cases have been published concerning Hebrew children who became 
 infected as a result of circumcision practised according to the rite, 
 requiring the operator to arrest hemorrhage by oral suction. Modern 
 researches have demonstrated the anatomical tubercle to be a gen- 
 
ETIOLOQ V OF INFECTIONS. 69 
 
 uine bacillary tubercle. II. is well to remember thai direct inoculation 
 may occur from bovidse to man. The observation reported by 
 Pfeiffer is a most remarkable one. Moser, a veterinarian of Weimar, 
 wounded himself in making a necropsy upon a tuberculous cow. 
 months later a cutaneous tuberculosis developed al the point of the 
 cicatrix, lie died from pulmonary tuberculosis two and a balf 
 after infliction of Hie wound. Tscherning and Ponfick love cited 
 similar cases. The researches of Verneuil and of Femel have fully 
 demonstrated the transmissibility of tuberculosis by sexual inter- 
 course. Cornil and Dobroklonsky produced tuberculosis in guinea- 
 pigs by injecting bacilli into (heir vaginal canals. 
 
 Transmission of Infections through the Air. Alter the con- 
 tagious elements have passed out of the diseased body they may 
 be dispersed by the air, transported by water, and reside in the soil, 
 awaiting an occasion to invade a new organism. 
 
 Transmission by the air, although not of such frequent occurrence 
 as was formerly believed, is, nevertheless, undeniable. The air con- 
 tains a great number of microbes, as is shown by the following figures 
 obtained by Miquel. These figures demonstrate the considerable 
 variations observed in different localities: 
 
 On sea, at 100 kilometres from the coast . . . 0.6 
 
 Altitude of 2000 metres 3.0 
 
 Summit of the Pantheon 200.0 
 
 Observatory of Montsouris ...... 480.0 
 
 Rue de Rivoli . 3,480.0 
 
 New houses ......... 4,500.0 
 
 Sewers of Paris 6,000.0 
 
 Old houses 36.000.0 
 
 Hotel Dieu . 40,000.0 
 
 Hopital do la Pitio 79.000.0 
 
 In perusing this table it is surprising to note that the air of sewers 
 does not contain many more microbes than that of a new house, anil 
 contains one-sixth as many as the air of an old house. The reason 
 for this is that the innumerable bacteria residing in the water cannot 
 enter the air. This has been demonstrated by experiments: a cur- 
 rent of air passing over a contaminated liquid does not take up 
 microbes. 
 
 The various figures above given have but a relative value. Con- 
 siderable variations occur each day in the same locality. The number 
 of microbes increases when a violent wind raises the dust, and dimin- 
 ishes after a rain which sweeps them down toward the soil. During 
 the hot season the microbes increase. According to Dr. Miquel. the 
 
70 INFECTIOUS DISEASES. 
 
 average number of bacteria contained in the air of Monsouris is 
 170 in winter, 295 in spring, 345 in summer, and 195 in autumn. 
 The highest figures were found in July and the lowest in De- 
 cember. 
 
 It has generally been thought sufficient to count the number of 
 microbes in the air without ascertaining the proportion of pathogenic 
 agents. However, Ullmann detected staphylococci in the air of a 
 surgical ward, and Eiselsperg and Emmerich found streptococci. The 
 latter microbe seems to be quite widely distributed in the atmos- 
 phere, or at least a variety of it is quite frequently met with in 
 decaying substances. It has also been demonstrated that air may 
 convey the contagium of diphtheria, typhoid fever, and the eruptive 
 fevers. As already stated, however, this is seldom the case. Even 
 influenza does not attack those persons who have not been in contact 
 with those suffering from the malady, and, although its propagation 
 is often rapid, it is not any more so than our means of communica- 
 tion. Epidemics are engendered not by the air but by the agency 
 of individuals. 
 
 Transmission of Tuberculosis by Inhalation. From a bac- 
 teriological standpoint, the air expired from the lungs of a tuber- 
 culous patient is pure, since it contains no tubercle bacilli or any 
 other microbe. The real danger resides in the expectoration. Pro- 
 tected by the organic particles in which it is incorporated, the ba- 
 cillus retains its vitality in the dried sputa for a long period and is 
 distributed far and wide. The protected bacillus is more dangerous 
 than the free microbes, because the animal and vegetable detritus 
 containing it act as foreign bodies and give rise to inflammatory 
 reactions which favor " tuberculization." 
 
 Numerous experiments have proved that inhalation is a far more 
 certain mode of contagion than ingestion. In this connection, Tap- 
 peiner's researches upon dogs leave no room for doubt. 1 
 
 It is not correct, however, to say that the bacilli are carried by 
 the dried sputa alone. The researches of Fluegge and his disciples, 
 which have been confirmed by Moeller, have established that a con- 
 sumptive, when speaking or coughing, projects about him a sort of 
 microscopic spray of mucus and saliva charged with tubercle bacilli. 
 The persons surrounding him are thus exposed to the danger of con- 
 tracting the disease. 
 
 1 Tappeiner. TJeber eine neue Methode Tuberculose zu erzeugen. Vircliow's Arch., 
 1878. Neue exp. Beitrage zur Inhalationtuberculose. Ibid., 1880. 
 
ETIOLOGY OF INFECTIONS. 71 
 
 Conveyance of Infection by Water. The transmi ion of infec- 
 tious diseases through the agency of water is far more frequenl 
 
 than by means of the air. This fact was known to the anciente, who 
 used aromatic infusions as beverages, thus employing a very rational 
 method of sterilization. In passing through the soil, water free 
 itself of microbes. Spring water, therefore, when taken a! its ource, 
 is often absolutely sterile. For this to occur, however, water must 
 percolate through porous st rata, When \\ filters through calcareous 
 strata, making its own little channel, it retains its microbes. Such 
 are the waters of Avre and Vanne, which supply Paris. 1 A- 3oon as 
 it enters upon its course, spring water begins to acquire bacteria. 
 Even hot mineral spring water contains bacteria. 
 
 It is readily understood that bacteria become more numerous when 
 a water-course traverses a city. We must remember, however, thai 
 running water purifies itself quite rapidly. The following figures 
 are convincing: The water of the Izar before its passage through 
 Munich contained 305 bacteria per cubic centimetre. At its exit 
 from the city, after having received the contents of the sewers, it 
 contained 12,600 per cubic centimetre. Thirteen kilometres further 
 down the figure is reduced to 2400 per cubic centimetre. This 
 natural depuration is likewise effected in reservoirs. The water of 
 the Thames, for instance, contains 1437 bacteria per cubic centi- 
 metre. It contains only 318 per cubic centimetre after its passage 
 into a first reservoir, and 177 per cubic centimetre at its exit from 
 a second. As already stated, the action of the sun is more powerful. 
 Fewer microbes are found at 8 p.m. than early in the morning. The 
 number may thus fall from 520 to 5 per cubic centimetre. 
 
 Epidemiological and bacteriological researches have led to prophy- 
 lactic principles of importance. The water origin of typhoid fever, 
 cholera, and dysentery seems to be definitely established. In regard 
 to typhoid fever, the history of epidemics is at least as important as 
 bacteriological researches, since it is difficult to separate and differ- 
 entiate the colon bacillus from the typhoid bacillus, when these two 
 microbes are present in the same fluid. The errors that have been 
 made in this respect, however, have led to wise hygienic precautions. 
 At the same time a more minute study of pathogenesis has developed 
 new ideas concerning the origin and spread of infections. It has been 
 questioned whether the role of water was not a complex one ; whether. 
 
 1 Thoinot. Lcs sources tie la craie et la fievre typhoidc. Presse medicate. Feb. 14. 
 1900. 
 
72 I -XFECTIO US DISEASES. 
 
 in addition to the possible presence of pathogenic agents, it was 
 necessary to weigh the action of saprophytes capable of favoring 
 their development. Authorities are now inclined to admit this 
 theory with regard to cholera and typhoid fever. It accounts for 
 those cases in which the disease attacked persons who had drunk 
 from a reservoir polluted by percolations from cesspools. Typhoid 
 fever has developed even when the matters were derived from indi- 
 viduals free from this disease or who had suffered from it a year 
 before. At the end of so long a period the bacillus was certainly 
 destroyed. In fact, according to the researches of Karlinski, it is 
 known that the microbe does not survive in fecal matters for more 
 than three months. This fact, which is often cited in support of the 
 specific origin of the disease, seems rather to lead to a contrary 
 conclusion. 
 
 Whatever mode is responsible, it is certain that water causes the 
 majority of epidemics and explains their recrudescence in regions 
 where the disease is endemic. In this connection nothing is more 
 instructive than the researches of Drs. Brouardel, Chantemesse, and 
 Widal. These authors showed that, in Paris, in 1885, 1886, and 
 1887, typhoid fever suddenly increased twelve or fifteen days after 
 the population was supplied with river water, and disappeared as 
 soon as spring water was again furnished. 
 
 The survival of germs in water has been studied by various authori- 
 ties. Straus, Dubary, and Hochstetter have produced figures in 
 evidence of the effects exerted by diverse conditions, such as the 
 composition of the water, presence of other microbes, dissolved sub- 
 stances, and the action of carbonic acid, as, for example, in seltzer 
 water. In this connection it should be remarked that carbonic acid 
 under pressure confers no germicidal property upon seltzer water. 
 Although the non-sporulating anthrax bacillus dies in it within an 
 hour, the typhoid bacillus resists for from five clays to twelve days, 
 that is, about the same as in ordinary water. 
 
 The conclusion is that water furnished for drinking purposes 
 always contains microbes. 
 
 Transmission of Infections by the Soil. The soil receives as 
 many microbes as does water. These sink deep into the soil, but 
 no further than three and one-half to four yards below the surface. 
 At this depth the soil becomes sterile. The maximum is found at 
 twenty inches (C. Fraenkel). Those remaining upon the surface are 
 rapidly destroyed by the sun's rays. However, a little soil or dust 
 
ETIOLOGY OF INFECTIONS. 
 
 taken at the surface of I, he road almost constanl ly Ikw ome patho- 
 genic, agents: pyogenic cocci, the bacillu of gaseou gangri 
 tetanus, and in certain localities the bacillus anthracis, Clinical 
 studies supplementing the data of bacteriological research have 
 
 established the telluric origin of the agents of <l.\ cholera, 
 
 typhoid fever, tuberculosis, and icterus gravis. These various ag 
 
 as above stated, are found in and nol upon the surface of the -oil. 
 They are brought to the surface on various occn-ions when 
 
 instance, the soil or streets are dug or torn up for diverse pur} 
 Such work is too often followed by the outbreak of epidemii 
 typhoid fever, diarrhea, or icterus gravis. 
 
 Role of the Invertebrates in the Transmission of Infections. 
 It has long been known that certain pastures were particularly dan- 
 gerous as centres of anthrax infection. In Beauce such pastures 
 were called "cursed fields." At times the focus was confined to a 
 farm or a stable. Pasteur undertook the study of this mysterious 
 question and discovered anthrax spores in the infecting soil in the 
 neighborhood where anthrax animals had been buried several years 
 before. Pasteur asserted that earthworms ingested the spores with 
 the contaminated soil and, coming to the surface, deposited them 
 with their excreta. Koch vigorously opposed Pasteur's theory. He 
 argued that the soil is too cold to permit the vegetation and particu- 
 larly the sporulation of anthrax. The soil, however, seems to be a 
 good culture medium. Soyka 1 proved by experiment that the intro- 
 duction of particles of quartz into liquids in which bacteria are culti- 
 vated markedly favors sporulation. It is further to be remarked 
 that the temperature of the soil is higher around buried cadavers 
 because of the heat generated by putrefaction. 
 
 Earthworms are not the only animals capable of conveying anthrax. 
 The highly interesting experiments of Karlinskr demonstrate that 
 snails may play the same role. Living spores were found in their 
 intestines eleven days after ingestion of food containing anthrax 
 bacilli. Insects, particularly flies, are often the agents of microbic 
 transmission. At times the3 f simply transport the germs from one 
 point to another. At other times they inoculate them into healthy 
 individuals. The typhoid bacillus passes through the intestine of 
 the fly without perishing. Flies may also disseminate the tubercle 
 
 1 Soyka. Bodenfeuchtigkeit uud Milzbrandbaeillus. Fortschritte d. Med.. l xv 
 
 2 Karlinski. Zur Kenntniss der Verbreitungswege des Milzbraudes. Centralbl. f. 
 Bakt., 1889, Bd. v. 
 
74 INFECTIOUS DISEASES. 
 
 bacillus, as has been proved by Spillmann, Haushalter, Hoffmann, and 
 Moeller. As, however, the common fly is incapable of biting man, it 
 simply diffuses the virus. 
 
 The role of mosquitoes is much more important. As early as 1848 
 Nott believed they conveyed yellow fever. In 1898 Grassi estab- 
 lished the law of coincidence of malaria and certain mosquitoes — 
 the Anopheles and especially Anopheles claviger. The bite of Culex 
 pipiens is less dangerous, though not completely harmless (Laveran, 
 Bignami, Bastianelli, etc.). It is also known that the African 
 cattle disease caused by the tsetse fly is not due to venom, as was 
 once supposed, but to inoculation of a parasite, trypanosoma Evansi. 
 Bed-bugs may transport tuberculosis (Dewevre) and recurrent fever 
 (Tiktine), while spirilla die inside these animals in forty -eight hours. 
 The majority of other microbes perish very rapidly, so that, according 
 to Nuttal's experiments, bed-bugs do not seem to be capable of 
 propagating anthrax or bubonic plague. Ogata has shown that fleas 
 found upon rats suffering from plague often contain the pathogenic 
 bacillus. The flea of the rat is not, however, identical with that of 
 man, and seems to be incapable of biting him. 
 
 All these extremely interesting facts tend further to reduce the 
 role of the air and to establish the conclusion that infections are most 
 frequently propagated by contact. 
 
 Role of Objects, Clothing, and Draperies. As early as 1868 
 Villemin rightly declared that " residences are foci of infection for 
 man, and should be disinfected as is a stable contaminated by glan- 
 ders." The floors, rugs, draperies, all furniture, and particularly 
 clothing, may receive and carry infectious germs. Numerous in- 
 stances demonstrate that clothing may cause the reappearance of an 
 infection several years after exposure. Such, for example, was the 
 case with the clothing of a child, the victim of diphtheria, which had 
 been placed in a drawer and thus protected against the action of 
 light. A year or two later, when taken out, they gave rise to fresh 
 cases of diphtheria. Hence the necessity for vigorous disinfection 
 of apartments, bedding, clothing, and vehicles of transportation 
 which have served for the conveyance of a sufferer from some infec- 
 tious disease. 
 
 Role of Plants. Infections may also be due to contamination 
 by plants carrying pathogenic agents. This is particularly the case 
 in aspergillosis and actinomycosis. The former disease attacks those 
 who rear pigeons, not because the birds are diseased, but because 
 
ETIOLOQ )' OF INFECTIO 75 
 
 fche individuals who feed them pul into their own mouths grain 
 contaminated with aspergillus fumigatus. Actinomyco 
 rarely contracted from men or animals. Man and the bovidae are 
 almost always infected through the agency of contaminated eai 
 corn or grain when the latter are chewed or (lie subjects are pri 
 by thoin. 
 
 Role of Aliments. Infections may be transmitted through inj 
 tion of meat, viscera, and milk of diseased animals. 
 
 Some authorities claim that the flesh of animals suffering from 
 anthrax may be consumed with impunity. According to Johne, the 
 meat contains no spores. This assertion is contradicted by the 
 experiments of Schmidt-Muhlheim. This scientisl showed that Johne 
 had examined only the interior of the meat, and that sporulation i- 
 possible upon the surface in contact with air. Such flesh should be 
 proscribed, if for no other reason than to avoid the danger to which 
 those who handle it are exposed. In the German statistics for I s ^7 
 it is found that anthrax developed twelve times through the use 
 of contaminated meat. According to Puech, salting may destroy 
 virulence. The experiments of Foster and Freytag contradict this 
 conclusion. By growing anthrax in agar-agar containing an excess 
 of salt these authors discovered that, while the bacilli died in twenty- 
 four hours, the spores survived for several months. It must be 
 remembered that the milk of animals infected with anthrax may con- 
 tain virulent bacteria, as has been established by the researches of 
 Chambrelent, Moussous, and Karlinski. 
 
 As regards the flesh of tuberculous animals, the Congress of l sss 
 demanded the total proscription of such meat. It is as yet difficult 
 to express a final opinion in this respect. A certain number of 
 tradictory experiments have been reported. Cooking and the action 
 of the gastric juice do not suffice to destroy the tubercle bacillus. 
 Finally, although the microbe is not present in the muscles it is 
 with in the glands, and this, perhaps, is a sufficient reason for pro- 
 hibiting the consumption of such meat. 
 
 Role of Milk. Since Gerlach recognized that the milk of dist , - 
 cows may transmit tuberculosis, numerous experiments have con- 
 firmed his view and demonstrated the role of this fluid in the etiology 
 of abdominal tuberculosis in children ( Klebs, Orth, Cohnheim). From 
 a hygienic standpoint, Gerhardt published an extremely interesting 
 work upon this subject. Milk purchased in ten different places in 
 Munich did not transmit tuberculosis. On the other hand, the milk 
 
76 IXFECTIOCS DISEASI-JS. 
 
 of consumptive cows always proved virulent. When this milk was 
 diluted with forty to one-hundred volumes of non-infected milk, 
 however, it was rendered harmless. This is just what occurs in 
 dairies. The researches of Bang demonstrated the presence of vir- 
 ulent bacilli in butter. Heating of milk is, therefore, absolutely 
 necessary. In this connection it should be remembered that a tem- 
 perature of 65° C. (149° F.), and even 70° C. (158° F.), is not always- 
 sufficient to destroy pathogenic germs. Ingestion of milk thus 
 treated has resulted in the transmission of the disease to swine, 
 while rabbits, which are less sensitive to this mode of infection, 
 usually resisted infection (Bang). 
 
 Since the milk of tuberculous cows so often proves to be virulent, 
 we may justly assume that the milk of consumptive women is also 
 a source of danger to their offspring. Here, perhaps, is a cause of 
 infantile tuberculosis. We say "perhaps" for the reason that the 
 results of experimental researches have thus far been negative. 
 Escherich examined the milk of women suffering from pulmonary 
 tuberculosis, but he was unable to discover any bacilli. It seems, 
 however, that he did not make inoculation experiments. In 1892 
 Fecle studied the question more thoroughly. 1 He injected the milk 
 of tuberculous women into the subcutaneous cellular tissue, peri- 
 toneum, and anterior chamber of the eyes of rabbits and guinea-pigs, 
 and never observed the development of tuberculosis. These results 
 w r ere confirmed by Bonis. The experimental inoculations of Bang 
 w r ere likewise negative. The author observed a case which contra- 
 dicted the classical opinion and showed that the milk of a con- 
 sumptive ma3' possibly prove virulent. 2 
 
 The case in question was that of a woman, thirty-four years of 
 age, w 7 ho entered the hospital February 16, 1896, for a pharyngeal 
 tuberculosis. She was pregnant, and confinement occurred under 
 favorable conditions. From that moment the symptoms became 
 aggravated, and the woman died on the 24th of March, seventeen 
 days after childbirth. The necropsy showed advanced tuberculous 
 lesions in the lungs and gray granulations in the liver, kidneys, and 
 thyroid gland. 
 
 Two days after birth the child became jaundiced, and then green 
 
 1 W. Fcde. Transmissibilita della tuberculosi per lattazione. Congresso pediatrico 
 italiano. (Anal, in Riforma la Medica, 1892, vol. iv. p. 236.) 
 
 2 Roger et Gamier. Passage du bacille de Koch dans le lait d'une femme tuber- 
 culeuse. Soc. de biol., Feb. 24, 1900. 
 
ETIOLOQ v OF INFECTIONS. 77 
 
 diarrhea and edema of the lower extremities supervened. The 
 infant was first fed from the bottle, but the mother undertook to 
 nurse it when she observed thai il wag ill. Shegaveil her milk from 
 the loih to the L2th of March. Aggravation of her condition, : 
 ever, prevented her from further suckling her offspring. The child 
 lived six weeks. At the necropsy numerous tubercles were di 
 ered in the liver, spleen, kidneys, and mesenteric glands. On his- 
 tological examination of the liver typical tuberculous granulations 
 containing Koch's bacilli were found. 
 
 On March 11th, four days after confinement, two guinea-pigj were 
 inoculated with milk taken aseptic-ally from the mother's breast. One 
 guinea-pig, weighing 440 grams, received I c.cm. of the milk sub- 
 cutaneously; 2 c.cm. only were injected into the peritoneal cavity of 
 the second guinea-pig, which weighed 525 grams. The former 
 animal died much emaciated on the 14th day of April, and at the 
 necropsy presented typical lesions of generalized tuberculosis. The 
 other animal survived. It weighed 565 grams on April 21st, and 
 050 grams on June 14th. It presented hypertrophied glands in 
 the groin, however. It was killed on the 28th of the following 
 January. At the necropsy a fibrous peritonitis was found at the 
 point of inoculation. The intestinal coils were adherent to each 
 other and to the lateral wall of the abdomen. The omentum was 
 thickened and contracted, free from visible tubercles. The rest of 
 the abdomen presented no lesions. The surface of the liver was 
 studded with depressed points resembling cicatrices. Microscopic 
 examination of the viscera showed no tuberculous granulations, 
 sclerotic lesions, or bacilli. 
 
 Of the two guinea-pigs, therefore, only one became tuberculous. 
 The one which received the larger dose of the milk developed tuber- 
 culosis according to the usual mode, and death occurred in thirty- 
 three days. The other animal, which received half the amount of 
 milk injected into the former animal, survived and seemed to be in 
 excellent health when it was killed, ten months after inoculation. 
 It had not, however, remained absolutely immune. The injected 
 milk had not acted as an indifferent liquid, since a fibrous peritonitis 
 developed at the point of inoculation, and thus manifested the patho- 
 logical process that had taken place there. Moreover, a hypertro- 
 phied gland in the groin and traces of cicatrices upon the surface of 
 the liver proved that generalization had begun. The history of the 
 first guinea-pig enables us to explain the lesions present in the second 
 
78 ISFECTIO US DISEASES. 
 
 animal. In the former the quantity of injected bacilli was large 
 enough to overcome the resistance of the organism, and tuberculosis 
 was generalized. In the case of the second guinea-pig, the dose being 
 smaller, infection was abruptly arrested: the lesions were repaired 
 and common cicatrices only, without any characteristic elements, were 
 found. 
 
 It must be concluded that the injected milk contained bacilli, 
 and was, therefore, capable of transmitting tuberculosis. It is true 
 the child was exposed to sources of contamination other than that 
 of suckling. However, as the necropsy upon the child showed that 
 the lesions predominated in the mesenteric glands, liver, and spleen, 
 it is probable that the digestive canal was the principal if not the 
 only route of contamination. 
 
 Therefore, the milk of a tuberculous woman may, in exceptional 
 instances, serve as a vehicle for Koch's bacillus even in the absence 
 of appreciable tuberculous lesions in the mammary glands. 
 
 In the course of acute infectious diseases the milk of women seems 
 to be free of virulence. The unfavorable results of artificial feeding, 
 especially among the poorer classes, led me to allow sick mothers to 
 nurse their children. The first attempts were made in cases of 
 erysipelas, the writer having previously learned that the milk con- 
 tained no streptococci. Nine children were suckled by the mothers, 
 three others were allowed mixed alimentation in order to compen- 
 sate for the diminished amount of mother's milk. Under these 
 conditions all the children thrived. 
 
 Suckling was likewise continued in other diseases. Over one hun- 
 dred women suffering from measles, scarlatina, mumps, or sore 
 throat nursed their infants. Among these, two only contracted 
 measles, and then only in a very mild form. This immunity of 
 infants leads one to believe that the milk contains immunizing sub- 
 stances from the very beginning of the mother's illness. Whatever 
 the correct interpretation of the fact may be, the innocuousness of 
 suckling seems to be well established. 
 
 Autoinfections. 
 
 The reality of morbid spontaneousness is recognized and pro- 
 claimed by clinicians as is that of contagion. In fact, infectious dis- 
 eases are seen to develop without any accidental contamination. They 
 occur under conditions which preclude the intervention of external 
 
ETIOLOGY OF INFECTIONS. 7!> 
 
 germs. When an Individual baa an attack of pneumonia ae the 
 
 result of exposure to cold, w < • ; h times search in vain for some external 
 origin of infection. The same is true of cases of sore throat, erysip- 
 elas, osteomyelitis, and typhoid fever, in which the minute I inquiry 
 and the most attentive examination fail to reveal 8 focus oi contam- 
 ination. Therefore, a functional disturbance is supposed to have 
 been produced by some ordinary cause. 
 
 A diametrically contrary view arose when the advances of bacte- 
 riology revealed the animate agents of infect 'mns. Contamination by 
 a certain microbe was assumed to be necessary U>v the development 
 of every case of infection of a definite character. This simple theory 
 was not in harmony with clinical observation. The enthusiasm 
 aroused by new discoveries was so intense, however, that the unex- 
 plained facts of clinical observation were unhesitatingly denied. 
 
 Finally, science has succeeded in harmonizing the contradictory 
 and exclusive theories. Morbid spontaneousness is again admitted. 
 It rests, however, upon a new basis. An infectious disease often 
 appears to be due to a series of microbes which constantly reside 
 upon our mucous membranes and epidermis. Under normal condi- 
 tions the organism either does not permit these dangerous guest- to 
 penetrate into its interior, or it rapidly destroys those which pass 
 the epithelial barriers. When, however, the organism is disturbed 
 by some influence, the microbes invade it. Infection is then justly 
 said to have been spontaneous — i. c, to have developed without any 
 outward contamination . 
 
 Distribution of Microbes within the Normal Organism. It is 
 readily understood that microbes, being abundantly distributed 
 around us, must necessarily be encountered on every part of our 
 organism in contact with the external world. 
 
 At each inspiration a certain number of bacteria are carried with 
 the air into the respiratory passages. They are. however, arrested 
 in their course by various organs: by the hair in the nasal cavities, 
 by the vibrotile cilia of the bronchial mucous membrane, and by the 
 secretions, so that the air is often bacteriologically pure in the pul- 
 monary alveoli and even in the bronchioles. In sweeping back 
 through the respiratory tract the air does not take up any germs once 
 deposited, since, as has already been stated, microbes can never 
 leave liquid media. The expired air. therefore, contains no bacteria. 
 
 The respiratory apparatus is happily provided with various means 
 of protection against microbes. The secretions act mechanically. 
 
80 INFEt ' TIO US DISEASES. 
 
 and, so to speak, wash the mucous membrane. A certain number 
 of bacteria are thus thrown out, others are destined by the nasal 
 mucus, which possesses, as Lermoyez and Wurtz have shown, a ger- 
 micidal power, viz., exert a sort of antiseptic action. The remainder 
 is incorporated and devoured by phagocytes which greatly abound 
 in the pulmonary alveoli and wherever lymphoid tissue is highly 
 developed. 
 
 Bacteria are found in far larger numbers in the alimentary canal. 
 The buccal cavity contains the most varied species, among which 
 some endowed with pathogenic properties are almost constantly 
 present. Such are the pneumococcus, the streptococcus, and the 
 micrococcus tetragenus. The gastric juice has not such germicidal 
 power as was formerly believed, since recent enumerations demon- 
 strate that this portion of the alimentary tract contains large num- 
 bers of bacteria, even more than the duodenum. 
 
 The microbes find in the intestines conditions most favorable to 
 their existence. They are in nowise disturbed by the secretions 
 elaborated there, and they find an abundant supply of food. It 
 may, therefore, be said that the intestine is the paradise of microbes. 
 The following figures, borrowed from the interesting contributions 
 •of Gilbert and Dominici, show how well they thrive there : 50,000 
 microbes per cubic millimetre are found in the stomach. In the first 
 part of the duodenum the number is only 30,000 per cubic milli- 
 metre. From this point the number progressively increases until 
 the lower portion of the intestine is reached, where the maximum 
 number, 100,000 per cubic millimetre, is found. In the cecum 
 another fall occurs, and throughout the large intestine the number 
 is 25,000 to 30,000 per cubic millimetre. When the quantity of fecal 
 matter contained in the alimentary canal is taken into account, the 
 remarkable total of 411,000,000,000 of microbes is reached. 
 
 The digestive tract is protected against microbes in the same 
 manner as in other parts of the organism. The intestinal and pan- 
 creatic juices and the bile, though possessing no germicidal power, 
 serve to sweep away and expel both microbes and their toxins. 
 Those micro-organisms which pass through the mucous membrane 
 are arrested by the lymphoid structures, follicles, and glands of 
 Peyer, and by the numerous leucocytes which are constantly wan- 
 dering in this region and may even enter the cavity of the intestine. 
 Should any microbes escape these agents of destruction they are ar- 
 rested in the lymphatic glands and in the liver, where new defensive 
 
ETIOLOGY OF INFECTIONS. 81 
 
 measures are united. Should i hey pass furl her, they reach the lu 
 which are likewise endowed with germicidal power. We thu 
 
 how numerous arc I he defenses provided io antagonize i he intestinal 
 microbes, since the danger of invasion of the economy by resident 
 microbes is Found especially in the alimentary canal. 
 
 The genito-ujinary organs also contain bacteria, al Least in their 
 external portions. The researches of Stroganoff, Menge, and Kroe- 
 nig have shown that the vaginal secretion is richly endowed with 
 germicidal properties. If some inoffensive bacterium, such as the 
 bacillus pyocyaneus, or a pathogenic micro organism, such as the 
 streptococcus or the staphylococcus aureus, is deposited deep within 
 the vagina they are soon destroyed. 
 
 With regard to the urinary passages, it is admitted that bacteria 
 do not ascend the urethra and never penetrate the bladder, and since 
 the time of Pasteur it has repeatedly been stated that urine voided 
 aseptically does not decompose. Recent researches, however, tend 
 to demonstrate that such is not always the case. The investigation- 
 of Lustgarten, confirmed by those of Dr. Courtois in our laboratory, 
 show that the urine of healthy individuals frequently contains micro- 
 organisms. Lustgarten describes eleven species, one of them very 
 peculiar, namely, the streptococcus giganteus urethras, the chains of 
 which are composed of several hundreds and even more than a thou- 
 sand individual cocci. The length of the chain is equal to five or 
 six times the diameter of the field of the microscope. This strep- 
 tococcus is not pathogenic for rabbits. Five cubic centimetres of a 
 bouillon culture was injected into the veins, and in order to render 
 its action more efficacious we at the same time introduced 1 c.cm. of 
 a sterilized culture of bacillus prodigiosus. The result was negative, 
 since the animal manifested no disturbance. 
 
 Autogenic Infections. Of the microbes which are found in living 
 organisms under normal conditions, some always remain harmless; 
 others become pathogenic as soon as some unfavorable occur- 
 rence weakens the resistance of the economy. They can then pene- 
 trate the barriers and give rise to various lesions. Upon the skin 
 acne, furuncles, anthrax, and at times gangrene or erysipelas appear. 
 In the buccopharyngeal cavity : anginas and phlegmons of the tonsils. 
 in the respiratory apparatus: bronchites. bronchopneumonias, and 
 fibrinous pneumonia; in the intestines: diarrhea, either simple, 
 choleriform, or dysenteriform, etc., occur. The microbes may also 
 secondarily or primarily invade the organism at large and produce 
 
 6 
 
82 INFECTIOUS DISEASES. 
 
 septicemia or pyemia, and thus give rise to numerous visceral 
 lesions. 
 
 In this connection, typhoid fever requires special consideration. 
 As soon as an epidemic of this disease breaks out, the drinking water 
 is subjected to minute examination, and if a bacillus more or less 
 analogous to that of Eberth is encountered, the entire etiological 
 problem is believed to be solved. We are told that improved canali- 
 zation and pure water supply are the best means to overcome a 
 typhoid epidemic, and, in many instances, practice has amply justi- 
 fied this theory. 
 
 Some epidemiologists, however, refuse to accept a theory so exclu- 
 sive. The penetration of the bacillus into the organism does not 
 seem to them sufficient to elucidate the etiology of typhoid fever. 
 Army physicians, who are usually in a position to follow the course 
 of epidemics, constantly protest against the exaggerations of some 
 authorities. 
 
 Dr. Arnold in an article in the Dictionnaire encyclopedique, and Dr. 
 Kelsch, 1 in his treatise on epidemiology, seem to have gone to the 
 root of the question. 
 
 In view of the great readiness with which typhoid fever makes its 
 appearance as a result of overwork, and especially under conditions 
 of overcrowding, such as exists in the case of armies in camp, it may 
 well be questioned whether man does not carry within himself the 
 germ of the disease, and whether external contamination is really 
 necessary. 
 
 Kelsch 2 fully demonstrates that the role of overfatigue and of 
 crowding are potent etiological factors. These bring in their train 
 contamination of the soil and water. Typhoid fever, therefore, 
 invariably appears in camps, and particularly in permanent camps, 
 at the end of five or six weeks, when the men are exhausted by over- 
 work. It may be objected, however, that some of the men were sick 
 when they left the city, or that the disease was in the stage of incu- 
 bation. It is necessary, however, to pile up a good deal of the most 
 hypothetical reasoning in order to support the dogma of morbid 
 specificity. The etiology becomes singularly simplified and rational 
 when the malady is attributed to endogenic origin, that is to auto- 
 infection, or, in other words, when it is assumed that men carry the 
 germs of the malady in the form of saprophytes, and that overwork, 
 
 1 Kelsch. Traite des maladies epiderniques, Paris, 1894. 2 Ibid. 
 
ETIOLOQ v OF INFECTIONS. 83 
 
 by diminishing their vital existence, permit the transformation of 
 these saprophytes into pathogenic agenl i. 
 
 Admitting, however, i li;ii an animate agenl i indi pensable f or the 
 production of an infectious disease, and thai there are two orders 
 
 of microbes specific ;nnl imn specific the question ari e : to which 
 order does the microbe of typhoid fever Eberth'j bacilluf belong? 
 
 Most bacteriologists answer thai il belongs to the specific order. 
 Drs. Rodet and Roux have advanced a contrary opinion. According 
 bo bhem the typhoid bacillus is bul a variety of colon bacillus. As 
 is known, this theory provoked a greal deal of controversy. In fact, 
 confidence was gradually lessened as to the destructive character of 
 Eberth's bacillus, as the hitler was proved to have no absolute value. 
 Most recent researches, however, have furnished ;i new method for 
 recognizing the typhoid bacillus. The serum of an animal that has 
 been vaccinated against a duly verified specimen of this microbe is 
 employed and its agglutinating action noted upon the bacillus which 
 is to be identified. By the employment of this method, which seems 
 to be unassailable, Drs. Remlinger and Schneider 1 demonstrated the 
 presence of the typhoid bacillus in water obtained far from epidemic 
 foci, in the soil, and, what is of far greater consequence, in the ali- 
 mentary canal of individuals free from typhoid fever. The last fact 
 is, as has been said, of considerable interest, since it explains pre- 
 viously obscure facts and harmonizes bacteriology and epidemiology. 
 Dr. Kelsch is, therefore, right in stating, according to the data of 
 clinical observation, that typhoid fever may be produced by germs 
 carried in our bodies and which, although harmless saprophytes 
 under ordinary conditions, temporarily manifest virulent functions 
 under the influence of marked violations of hygiene, notably pro- 
 longed fatigue, defective regimen, ordinary pollution of water — all 
 circumstances which, by virtue of their combination, are so powerful 
 in creating a putrid state in the internal medium. 2 
 
 Such is the rational conception which we may at present form with 
 regard to the etiology of typhoid fever. It is the view which I have 
 advocated, in a study made some years ago. 3 These ideas, which 
 were described in detail by Dr. Bourgeois, 4 aroused bitter criticism. 
 
 1 Remlinger et Schneider. Contribution a l'etvuie du baeille typhique. Arm. de l'ln- 
 stitut Pasteur, January, 1S07. 
 
 2 Kelsch. Loc. cit., p. 463. 
 
 3 Roger. Etiologie et pathogenic do la fievre typho'ide. Presje medieale. March 17, 
 1S94. 
 
 4 Bourgeois. Etiologie et pathogenic de la fievre typhoide. The<e de Pari?. 1 - 
 
84 ISFECTIO US DISEASES. 
 
 The discovery of Drs. Remlinger and Schneider demonstrates beyond 
 all doubt the truth of the view to which I was led by an impartial 
 study of typhoid epidemics. 
 
 The Autogenous Origin of Various Specific Infections. Among 
 other diseases which, perhaps, at times appear spontaneously, diph- 
 theria should first be mentioned. Bacteriology has already estab- 
 lished the presence in the mouth of a bacillus analogous to that 
 discovered by Loeffler. Does this non-virulent pseudodiphtheria 
 bacillus represent an attenuated variety or a distinct species? 
 This is an important and as yet unsolved problem. Likewise the 
 spontaneous origin of gonorrhea cannot be admitted except with 
 the greatest reservation, viz., its appearance in the absence of sexual 
 intercourse, as in the well-known observation of Straus. 
 
 It may be asked wdiether the germs of the eruptive fevers are not 
 often present in the bodies of healthy individuals. My personal 
 statistics, covering 304 cases of measles, 340 of scarlatina, 69 of 
 varicella, and 38 of variola, show that in a great number of cases 
 the minutest inquiry fails to reveal any mode of contamination. 
 We merely present the question of the autogenous origin of these 
 various affections. A decision must be reached through bacterio- 
 logical investigation. In the case of eruptive fevers it may be as- 
 sumed that the mode of contamination is so often uncliscoverable 
 because their germs are perhaps widely distributed and because 
 some of these fevers, particularly measles, are contagious in the 
 prodromic stage, previous to all serious manifestations, when con- 
 tact is scarcely noticed. 
 
 Auxiliary Causes of Infections. 
 
 Meteorological and Seasonal Influences. The role of cosmic 
 influences has at all times been accepted. This is evidently due to 
 the fact, which is open to popular observation, that the frequency 
 of infections is subject to quite regular oscillations each year. The 
 accompanying table gives a resume of my personal statistics, and 
 shows plainly that, each year, infectious morbidity runs nearly a 
 parallel course. The minimum is observed in October and Novem- 
 ber. Then follows an increase which reaches the maximum in the 
 spring, from April to June or July. The figures of each year are 
 almost the same. It is to be noted that measles appears earlier in 
 the year than scarlatina, and reaches the highest point in April and 
 May. On the other hand, scarlatina increases until June. Although 
 
ETIOLOO V OF INFECTIONS. 
 
 less pronounced, variations of anginai of diphtheritic or other type 
 are, nevertheless, clear. 
 
 Measles. 
 
 L896 
 
 1897 
 
 L898 
 
 
 L900 
 
 
 Number of cases « • I » erved . 
 
 804 
 
 :;7U 
 
 398 
 
 
 370 
 
 1817 
 
 Oases with contagion . 
 
 7!» 
 
 s:: 
 
 71 
 
 89 
 
 
 
 Percentage 
 
 25.1 
 
 •J l ,8 
 
 
 24 
 
 17 
 
 „'l :: 
 
 1 'i-ici-iil.iyc i n 
 
 L9.5 
 
 is.:; 
 
 WIS 
 
 21 
 
 13 
 
 17 8 
 
 " women 
 
 ::n l 
 
 21.6 
 
 J'i il 
 
 i\ 
 
 17.6 
 
 
 " i he ii'-\i born 
 
 31.9 
 
 J7.!l 
 
 20 
 
 25.7 
 
 
 
 Satr/atitHi. 
 
 
 
 
 
 
 
 Number of cases observed . 
 
 :', in 
 
 mi 
 
 l'ir, 
 
 770 
 
 l::7 
 
 2213 
 
 Cases with contagion . 
 
 .".:; 
 
 18 
 
 75 
 
 174 
 
 53 
 
 373 
 
 Percentage 
 
 L5.5 
 
 1 II 
 
 15.1 
 
 22.3 
 
 12 1 
 
 li, - 
 
 Percentage in men 
 
 8.0 
 
 6.2 
 
 9.7 
 
 10 
 
 L2 6 
 
 l j .". 
 
 " women 
 
 21.1 
 
 14.4 
 
 19 
 
 25 
 
 
 20.1 
 
 Varicella . 
 
 
 
 
 
 
 
 Number of cases 
 
 69 
 
 52 
 
 45 
 
 32 
 
 117 
 
 :', 1 5 
 
 Cases with contagion . 
 
 23 
 
 14 
 
 '.) 
 
 1 
 
 44 
 
 'H 
 
 Percentage 
 
 33.3 
 
 20.9 
 
 20 
 
 :;.l 
 
 37.0 
 
 J- - 
 
 Variola. 
 
 
 
 
 
 
 
 Number of cases 
 
 38 
 
 20 
 
 2 
 
 1 
 
 928 
 
 989 
 
 Cases with contagion . 
 
 14 
 
 8 
 
 1 
 
 1 
 
 246 
 
 •_'7< i 
 
 Percentage 
 
 36.8 
 
 40 
 
 50 
 
 100 
 
 20.5 
 
 27.3 
 
 The greatest number of cases of this kind are observed in May and 
 June. It is to be noted also that mumps is particularly prevalent 
 in April and May, and seldom occurs during the months of October 
 and November. 
 
 In this connection smallpox is a remarkable exception. The c 
 occur with nearly the same frequency throughout the year. 
 
 In the author's table the figures for erysipelas are those of the year 
 1900 onty. The variations here shown, however, are entirely com- 
 parable to those occurring in the eruptive fevers. 
 
 The influence of seasons is doubtless ascribable to manifold car,- - 
 thermometric, barometric, and hygrometric variations, the action 
 of the sun, rain, wind, and thunder-storms, and the role of ozone are 
 causes readily perceived. Do these influences, however, affect the 
 morbid germs or the higher organisms? Both hypotheses have 
 equally competent defenders. It seems that the lower the animal or- 
 ganism, the better it resists cosmic variations. Variations in pressure 
 and temperature which would rapidly kill a mammalian act indif- 
 ferently upon bacteria. It is more likely, therefore, that the recep- 
 tivity of the human organism is modified by disturbing meteoric 
 causes. It is difficult, however, to further elucidate this rather vague 
 problem. All that can be added is the fact that respiratory disturb- 
 
86 IXFECTIO US DISEASES. 
 
 ances are especially frequent when variations of temperature occur 
 and, principally, in the spring. Thoracic complications in the course 
 of infections such as erysipelas and variola are almost always ob- 
 served during the period from the month of March to the month of 
 May. On the other hand, heat favors the genesis of gastrointestinal 
 affections. 
 
 After the monthly variations, those embracing longer periods must 
 be considered. Variations in the cases of smallpox may be due to 
 negligence in the matter of vaccination. It is difficult, however, to 
 account for the changes occurring in a disease like scarlet fever. 
 A tabulation of our cases from 1896 to 1900 shows the number of 
 cases increasing progressively from 161 to 496, reaching a maximum 
 of 779, and then suddenly declining to 437. It is curious to note 
 that the variations in anginas correspond exactly to those occurring 
 in scarlatina. The eminent role of sore throat in the symptoma- 
 tology of scarlatina lends a certain interest to this parallelism. 
 Measles, on the contrary, presents almost no variation. On an 
 average, we receive from 360 to 380 cases annually. As in the case 
 of frequency, the gravity of cases undergoes periodical variations. 
 The history of scarlatinal epidemics observed in England and of 
 epidemics studied by Bretonneau in Tours clearly demonstrates this. 
 
 The influence exerted by climate is still more marked than in the 
 case of seasons. There are countries in which certain infectious dis- 
 eases cannot become acclimated. Yellow fever, which claims so 
 many victims in certain portions of the new world, seldom appears 
 on the old continent. 
 
 In this respect the sanitary conditions of a country are of the 
 greatest importance. The number of infectious cases has consid- 
 erably diminished since the advance of disinfection, the creation of 
 special hospitals for the isolation of contagious cases, and the im- 
 provement of drinking water. Even typhoid fever is at present less 
 frequent. 
 
 Influence of Race and of Family. Morbid receptivity varies con- 
 siderably in different races. The negroes are immune from certain 
 infections, such as yellow fever, and very seldom suffer from ma- 
 laria. On the other hand, they are very susceptible to tetanus. 
 
 The yellow race is predisposed to variola, which prevails in China 
 in an endemic form. 
 
 Acute articular rheumatism is confined almost exclusively to the 
 Caucasian race. 
 
ETIOLOQ V OF INFECTIONS. 
 
 87 
 
 If we pass from race to family we encounter analogou 
 There are families particularly sensitive to tuberculosi . or diphthe- 
 ria, or erysipelas. From this point of view I have questioned 956 
 men and KM I women suffering from erysipela . Many of them were 
 incapable of giving any information. Taking into account , how< 
 flic accurate replies, I liml iliat erysipelas existed in the familii 
 94 men and L10 women, which gives a ratio of 9.8 per LOO for the 
 former and L0.5 for the latter. Simple coincidence does qoI ade- 
 quately account for so high a proportion. Moreover, our figures 
 below the actual number, as many patients were unable to state 
 whether their parents had ever had an attack of erysipelas. The 
 following table gives the family history of this affection and .-hows 
 that, in many instances, the parents had several attacks and the 
 malady ran through several generations: 
 
 I'm . nis having ■ 
 
 II,,, 
 
 Father 
 
 Mother 
 
 Father and mother 
 
 Grandmother 
 
 Grandmother and father 
 
 Grandmother and mother 
 
 Brother or sister 
 
 Father and brother 
 
 Mother and sister 
 
 Uncle and aunt . 
 
 Children . 
 
 21 
 
 8 
 
 54 
 
 37 
 
 2 
 
 3 
 
 7 
 
 11 
 
 7 
 
 2 
 
 7 
 
 3 
 
 22 
 
 17 
 
 22 
 
 1 
 
 3 
 
 1 
 
 4 
 
 5 
 
 3 
 
 5 
 
 152 
 
 
 In the majority of cases contagion is not to be thought of, for the 
 children were either far removed from the parents or erysipelas 
 appeared after the death of the latter. One of the most curious 
 observations in this respect is that of a man, fifty-five years of age. 
 whose mother had experienced twelve attacks of erysipelas. He, 
 himself, was suffering from his fourteenth attack. While he was 
 under treatment in our wards, his son, who was enlisted in a regi- 
 ment of dragoons in Sedan and had not seen his father for over six 
 months, had his first attack of facial erysipelas. On other occasions 
 I observed two sisters who, although not residing together, synchro- 
 nously contracted facial erysipelas, and. what was more curious, the 
 affection assumed a wandering course in both, and invaded the 
 greater part of the trunk. 
 
 It seems that the streptococcus, like many other microbes, finds 
 in certain families a soil particularly favorable for its development. 
 
88 INFEQTIO US DISEASES. 
 
 Individual Immunity and Predisposition. There are numerous 
 individual variations; some persons have often exposed themselves 
 to contagion, even to vaccination, without being contaminated. A 
 great number of cases have been reported in which vaccination has 
 not taken. The same thing is at times observed in laboratories. 
 One animal resists, while others, apparently similar, placed under 
 identical conditions and inoculated in the same manner, die without 
 exception. 
 
 In some cases, insensible gradual vaccination may account for 
 individual immunity. The natives of Paris, for instance, do not, as 
 a rule, contract typhoid fever, which does not spare all individuals 
 arriving from the country. The reason is that Parisians from their 
 infancy have been little by little impregnated with the germ. Thus 
 becoming gradually habituated, they have either suffered no distur- 
 bance or manifested symptoms too mild and vaguely characterized 
 to be traced to their true course. 
 
 Insensible vaccination also explains the disappearance of epi- 
 demics. If, at a given time, the cases diminish in number and sever- 
 ity, this is clue to the fact that the population has slowly been 
 subjected to insensible vaccination. The immunity of physicians is 
 clue to no other cause. 
 
 The fact that an infection loses its gravity in the course of cen- 
 turies, or acquires unusual malignancy when it invades a people until 
 then immune, may be attributed to an analogous process. The 
 epidemics of measles in the Faroe Islands clearly illustrate this fact. 
 The disease was imported into these islands in 1846. Of the 7782 
 inhabitants, 6000 were attacked, the aged alone being spared. In 
 1875 the same malady invaded the Fiji Islands and killed 40,000 
 persons out of a population of 150,000. 
 
 Influence of Age, Sex, and Accidental Disturbances. Morbid 
 aptitude varies considerably with age. During intrauterine life the 
 fetus is exposed to some diseases the germs of which are transmitted 
 through the placenta. At the time of birth the individual offers 
 sufficient resistance to the majority of infections; vaccination does 
 not take, eruptive fevers, as well as typhoid fever and diphtheria, are 
 altogether exceptional. On the other hand, erysipelas, which is gen- 
 erally localized in the navel and almost invariably proves fatal, is 
 very readily contracted by the newborn. 
 
 Infectious diseases are frequent during childhood. At this epoch 
 of life the tissues are particularly apt to permit the development of 
 
ETIOLOGY OF INFECTIONS. 
 
 89 
 
 parasites. Pityriasis, for instance, doc-; not thrive in the aged, and 
 spontaneously disappears with the advance of year 
 The frequency of infections diminishes with age. In the aged 
 
 scarcely any other disorders than vesical infection and pneumonia 
 occur. Does (lie immunity of old age depend upon previous di i 
 and insensible vaccination? Not altogether. A certain influence 
 
 must, be attributed to the modifications produced in the chemical 
 constitution of the tissues and humors. This is proved by the fad 
 that when measles invaded the Faroe Islands only the aged were 
 spared by the disease, which was unknown up to that time. 
 
 The influence of sex is no less interesting. It seems thai women 
 are predisposed to the infections of childhood for a longer period than 
 men. The eruptive fevers, which are <|uite rare among men after 
 the age of twenty years, are frequently observed among women 
 between twenty-five and thirty years of age. 
 
 The following table presents the results of my personal observa- 
 tions from this point of view: 
 
 
 
 Measles. 
 
 
 
 
 
 
 
 Men. 
 
 Women. 
 
 Tola' 
 
 Before 2 
 
 years 
 
 
 . 160 
 
 194 
 
 354 
 
 2 to 14 
 
 years 
 
 
 . 119 
 
 122 
 
 241 
 
 15 to 20 
 
 " 
 
 
 . 300 
 
 224 
 
 524 
 
 21 to 25 
 
 it 
 
 
 128 
 
 247 
 
 375 
 
 26 to 30 
 
 " 
 
 
 82 
 
 120 
 
 202 
 
 31 to 35 
 
 " 
 
 
 3S 
 
 42 
 
 so 
 
 36 to 40 
 
 " 
 
 
 13 
 
 16 
 
 29 
 
 41 to 45 
 
 " 
 
 
 4 
 
 5 
 
 9 
 
 46 to 50 
 
 " 
 
 
 1 
 
 1 
 
 2 
 
 51 to 60 
 
 " 
 
 
 1 
 
 
 1 
 
 Total 
 
 
 
 846 
 
 971 
 
 1S17 
 
 Adults 
 
 above 15 years 
 
 Scarlatixa. 
 
 567 
 
 655 
 
 1222 
 
 
 
 
 Men. 
 
 Women. 
 
 Total. 
 
 Before 2 
 
 years 
 
 
 29 
 
 27 
 
 56 
 
 2 to 14 years 
 
 
 . 22S 
 
 202 
 
 430 
 
 15 to 20 
 
 tt 
 
 
 . 388 
 
 369 
 
 757 
 
 21 to 25 
 
 ti 
 
 
 167 
 
 33S 
 
 505 
 
 26 to 30 
 
 n 
 
 
 So 
 
 167 
 
 252 
 
 31 to 35 
 
 " 
 
 
 44 
 
 82 
 
 1 26 
 
 36 to 40 
 
 " 
 
 
 19 
 
 29 
 
 4-- 
 
 41 to 45 
 
 tt 
 
 
 9 
 
 s 
 
 17 
 
 46 to 50 
 
 " 
 
 
 4 
 
 8 
 
 12 
 
 51 to 60 
 
 " 
 
 
 2 
 
 8 
 
 10 
 
 Total 
 
 
 
 . 975 
 
 1238 
 
 2213 
 
 Adults 
 
 above 15 years 
 
 
 71S 
 
 1000 
 
 1727 
 
90 
 
 INFECTIOUS DISEASES. 
 
 V UUCELLA 
 
 Before 2 years 
 2. to 14 years 
 15 to 20 , •■ 
 21 to 25 " 
 26 to 30 " 
 31 to 35 " 
 36 to 40 " 
 41 to 45 " 
 46 to 50 " 
 
 Total 
 
 Adults above 15 years 
 
 Before 2 years 
 2 to 14 years 
 15 to 20 " 
 21 to 25 " 
 26 to 30 " 
 31 to 35 " 
 36 to 40 " 
 41 to 45 " 
 46 to 50 " 
 51 to 60 " 
 61 to 91 ', 
 
 Total 
 
 Adults above 15 vears 
 
 Variola. 
 
 Mai. 
 
 Women. 
 
 Total. 
 
 57 
 
 46 
 
 103 
 
 69 
 
 54 
 
 123 
 
 IS 
 
 10 
 
 34 
 
 17 
 
 10 
 
 27 
 
 S 
 
 6 
 
 14 
 
 4 
 
 3 
 
 7 
 
 2 
 
 2 
 
 4 
 
 
 2 
 
 2 
 
 1 
 
 
 1 
 
 176 
 
 139 
 
 315 
 
 50 
 
 39 
 
 S9 
 
 Men. 
 
 Women. 
 
 Total 
 
 20 
 
 12 
 
 32 
 
 40 
 
 22 
 
 62 
 
 SS 
 
 59 
 
 147 
 
 80 
 
 105 
 
 185 
 
 50 
 
 105 
 
 155 
 
 56 
 
 71 
 
 127 
 
 45 
 
 55 
 
 100 
 
 27 
 
 28 
 
 55 
 
 22 
 
 24 
 
 46 
 
 20 
 
 29 
 
 49 
 
 16 
 
 15 
 
 31 
 
 464 
 
 525 
 
 989 
 
 404 
 
 491 
 
 895 
 
 These figures show the influence of sex and age upon the frequency 
 of the eruptive fevers. From fifteen to twenty years of age measles 
 and scarlatina are more frequent among men than women. At 
 twenty they undergo a sudden fall in the male sex, while among 
 women they remain at a very high level. 
 
 The study of variola shows plainly the beneficial influence of vac- 
 cination. Children are not frequently attacked. The disease in- 
 creases after the age of fifteen years. The maximum for men is 
 reached from fifteen to twenty years of age. Among women the 
 frequency increases, exceeds that of the other sex, and remains high 
 from twenty-one to thirty years of age. 
 
 The variations according to sex are less marked for the other 
 infections. Thus, the author found that 134 men and 122 women 
 were attacked by diphtheria, and 385 men and 407 women by 
 anginas. According to the author's statistics, mumps seems to be 
 more frequent among men than women, as he has found 170 of the 
 former and only 65 of the latter affected with this disease. This 
 result is probably due to the greater gravity of the disease in men 
 
ETIOLOGY OF INFECTIONS. '.>] 
 
 and to the frequency of orchitis which compel them to enter the 
 hospital. 
 
 The different acts of genital life invesl feminine pathology with 8 
 peculiar ('li:ii-:icici-. Menstruation may be an occasional can 
 infectious manifestations. Such, especially, is the case in erysip 
 an attack of which may attend each period. Certain women thus 
 experience fifty and sixty relapses. 
 
 Pregnancy m;i.y modify I he course of certain infections. Not infre- 
 quently tuberculosis seems to be arrested and, after confinement, the 
 disease assumes a, more rapid course ll is hardly necessary to refer 
 to the frequency of puerperal infections. In this case, however, the 
 diseases present nothing special. The puerperal woman ie in the 
 same situation as a wounded one 
 
 All violations of the laws of hygiene predispose to infection-. The 
 noxious effects of overcrowding have already been referred to. The 
 influence of previous diseases is well known. Some of them predis- 
 pose to infections. Diabetes favors the development of pyogenic 
 microbes and of the tubercle bacillus. Pneumonia, erysipelas, and 
 rheumatism, far from conferring immunity, predispose to new 
 attacks. As a rule, however, infections create a refractory state and 
 prevent future attacks. It is well to add, however, that immunity 
 is in no case absolute except, possibly, in syphilis. 
 
 Among causes which lessen individual resistance, the influence of 
 external agents is of chief importance. Serious traumatism, crush- 
 ings, and extensive contusions diminish considerably the resistance 
 to invasion by microbes. 
 
 The action of cold and heat is very complex, for they do not act 
 simply by modifying the temperature of the body. The fact that 
 chickens, which are naturally immune to anthrax, contract this infec- 
 tion when they are exposed to cold, and that, on the contrary, frogs 
 lose their immunity when exposed to high temperatures, is not due 
 to modifications of the organic temperature thus produced in these 
 animals. In reality the phenomena are more complex. When 
 chickens are exposed to cold and frogs to heat, nutrition is disturbed: 
 the life of the cells, and consequently the constitution of the humors, 
 is altered; the heart, the nervous system, and the leucocytes are acted 
 upon. Abolition of immunity is, therefore, the result of manifold 
 factors. 
 
 Action of Poisons upon Infections. A great number of poisons 
 diminish the resistance of the organism to infectious agents. 
 
92 LXFECTIOUS DISEASES. 
 
 Seeck noticed that various parasites developed upon the skin of frogs 
 treated with metallic poisons. Some of the lesions observed in the 
 course of intoxications are in reality due to secondary infection. 
 Such is the case in mercurial stomatitis or enteritis. The mercury 
 during elimination by the mucous membranes denudes the latter of 
 their epithelium and prevents them from resisting invasion by the 
 numerous microbes swarming upon their surfaces. It is, therefore, 
 conceivable that mercurial stomatitis may be contagious, as in an 
 observation of Diday, which illustrates in a striking manner the 
 increased virulence which the buccal microbes may acquire in the 
 course of intoxications. 
 
 Poisons favor infection in two principal ways: in some instances 
 they produce local lesions which weaken the resistance of the tissues 
 into which the poisons are introduced; in other cases they give rise 
 to general disturbances of the economy, which abolish its immunity. 
 As an example of the former mechanism, we may cite the action of 
 lactic acid, which, when injected into the muscles of a rabbit, renders 
 this animal incapable of resisting symptomatic anthrax. Other sub- 
 stances, such as acetic acid, potassium acetate, and alcohol, produce 
 similar effects. Many antiseptic substances act in the same way. 
 Hence, the increasing tendency to substitute asepsis for antisepsis 
 in surgical practice or to utilize less energetic substances, such as 
 boric acid. 
 
 In other instances the process is one of general intoxication, affect- 
 ing probably the nervous system. Thus Platania demonstrated that 
 alcohol and chloral favor the development of anthrax in naturally 
 immune animals, such as the clog, the pigeon, and the frog. Wagner 
 verified the fact by inoculating anthrax into chickens treated with 
 chloral. 
 
 Influence of Autoinfections. A last group of poisons favoring 
 invasion by bacteria is represented by substances which originate 
 within the organis;n itself. Such occurs, for instance, in overworked 
 animals ; the toxins produced under these conditions favor the multi- 
 plication of attenuated viruses or the entrance of the numerous bac- 
 teria normally inhabiting the intestine. Diabetes and glycosuria 
 likewise induce infection as a result of chemical modifications. This 
 result, which has long been recognized by chemical observers, was 
 experimentally verified by Bujwid, who injected sugar into inocu- 
 lated animals, and by Leo, who administered to them phloridzin. 
 In both instances infection was facilitated or rendered graver. 
 
ETIOLOQ V OF INFECTIONS. 
 
 Certain organic lesions probably acl by disturbing the chemical 
 constitution of the organism. Neumann demon trated that the 
 development of the streptococcus may be favored by altering the 
 function of the liver, by modifying the alkalinity of the blood, by 
 
 producing lesions in (lie kidney, or by ligating the lower pari of the 
 intestine. In all these cases there is either excessive production of 
 toxic substances or insufficienl elimination. 
 
 Finally, microbes create morbid dispositions and favor the devel- 
 opment of secondary infections through the toxic substances which 
 they secrete. This fact will again be referred to when treating of 
 morbid associations. 
 
 Influence of Fasting. This influence was known to the ancients, 
 since epidemics following famines leave no doubl as to their con- 
 nection as cause and effect. Likewise, the frequency of infection-. 
 from tuberculosis to gangrene, in patients who cannot be nourished, 
 is a fact open to popular observation. The experiment- of Canalis 
 and Morpurgo demonstrated the role of starvation in this respect. 
 The resistance of the organism is reduced not simply by suppression 
 of alimentation, but also by insufficiency or bad quality of food. 
 The influence of such conditions was well observed by clinician-, 
 notably with reference to tuberculosis. The method of treatment 
 by overfeeding consumptives is the opposite of the mentioned con- 
 ditions. Analogous results are observed in experimental medicine. 
 I have discovered that rabbits, when abundantly nourished, fre- 
 quently resist inoculation of variola pus or culture, while similar 
 animals receiving ordinary rations succumb to this affection. This 
 observation led us to nourish patients suffering from smallpox, and 
 with satisfactory results. 
 
 The results are altogether different when we operate upon animals 
 which, after having been subjected to a sufficiently long period of 
 starvation, have again been supplied with their ordinary food for 
 several days. 1 Under these conditions the resistance is increased to 
 a remarkable degree, at least with regard to the colon bacillus. It 
 would not be correct to generalize the results which we have obtained 
 with the latter microbe, which is the only one with which we have 
 thus far experimented. 
 
 We starved five rabbits for five to seven days and then fed them. 
 Three to eleven days later we made intravenous injections of B. 
 
 1 Roger et Josue. Influence de l'inanition sur la resistance a rinfection coliba- 
 cillaire. Soc. de biologic, July 7, 1900. 
 
94 / NFEi TIO US DISEASES. 
 
 into them, as well as into control animals of equal or greater weight. 
 At this time the animals which had been subjected to fasting had 
 grown fat. but had not yet recovered their former weight. Of these 
 five animals; only one died, five days after the inoculation. Of the 
 five control animals, only one survived. 
 
 It may be asked whether fasting, as prescribed by certain religious 
 rites, is not of greater hygienic importance than is believed, and 
 whether the modifications produced by fasting do not finally 
 strengthen the defensive means of the organism. 
 
 Influence of Fatigue and Overwork. The accidents following 
 excessive fatigue have long held the attention of observers. Fatigue 
 diminishes the resistance to microbic diseases. If it is not permis- 
 sible to believe, as did the ancient veterinarians, that fatigue suffices 
 of itself to create glanders and anthrax, it may be admitted that it 
 favors or aggravates the development of these maladies. This is 
 clearly seen from the interesting observations collected by Solowieff 
 concerning both man and the horse. Clinical facts, however, are so 
 very complex that it is impossible to define the role of fatigue. The 
 infectious diseases developing in army camps are not altogether due 
 to the excessive work imposed upon the soldiers. The emotions, the 
 privations, the crowding, and other bad hygienic conditions must 
 also be taken into account. We, therefore, thought it well to transfer 
 the question to experimental ground, and with this end in view, we 
 pursued a certain number of researches upon animals. 1 
 
 We fatigued various animals — guinea-pigs, rabbits, white rats, 
 cats, dogs — and determined the influence of overwork upon the 
 results of inoculations. For this purpose we used the anthrax bacil- 
 lus and the bacillus of symptomatic anthrax. 
 
 General fatigue induced in animals inoculated either with anthrax 
 bacillus or the bacillus of symptomatic anthrax favors considerably 
 the development and generalization of infections. The overworked 
 animals invariably died before those left at rest. Quite often they 
 succumbed while the latter resisted. It must be noted that animals 
 of the same size and submitted to the same exercises by no means 
 possess the same morbid aptitude. Some resist better than others, 
 but these individual variations are observed in all experiments and 
 in nowise modify the meaning of the results which we have obtained. 
 
 If general, fatigue explains the development of infections, the over- 
 
 1 Charrin et Roger. Contribution a l'6tude experimentale du surmenage. Son 
 influence sur l'infection. Arch, de physiol., Feb. 19, 1890. 
 
ETIOLOQ v OF INFECTIONS. 
 
 work imposed upon an organ may account for certain clinical forms. 
 Cerebral rheumatism, for Instance, occurs only in individuals ad- 
 dicted to intellectual activity, or in those whose tiervou system has 
 suffered from late hours, dissipation, ambition, and disappointment. 
 Likewise, in young subjects, growing bonei are predisposed to 
 microbie localizations, ,-is expressed by i In- developmenl <<\ o 
 myelitis. Conversely, an inactive organ does noi offer a -oil for the 
 localization of microbes. Children suffering from mumps do not 
 develop orchitis; this localization does not occur until after pub) 
 
 Development of Epidemics; Their Variations with Countries 
 and Epochs. The facts above reported lend to the conclusion thai 
 in all infections two factors are to be taken into consideration : I 
 an external factor, the pathogenic microbe; (2) an internal factor, 
 the state of the organism. 
 
 The pathogenic microbe comes from without. It was primarily 
 a simple saprophyte, which accidentally settled in a living being, its 
 special organization enabling it to accommodate itself to the new- 
 medium. It thus loses its ability to thrive outside living organism-, 
 and acquires new qualities varying so greatly from the original that 
 it is impossible to refer the isolated pathogenic microbe to the sapro- 
 phytic species from which it evolved. 
 
 After the microbe has once acquired virulent properties it does 
 not remain immutable. On the contrary, it is modified by various 
 circumstances, its virulence increases or diminishes, and it acquires 
 a special aptitude to vegetate in certain tissues rather than in others. 
 The evolution of pathogenic microbes through the ages and countries 
 thus leads us to admit that the clinical types also cannot remain 
 immutable. It is conceivable that new infections may appear under 
 the influence of cosmic and many other fortuitous agencies, and that 
 affections of ancient origin may be modified or disappear. 
 
 In view of the fact that epidemics are at times suddenly revived 
 and reigning infections assume unusual gravity or exceptional mild- 
 ness, it must be admitted that infectious agents may become sud- 
 denly more or less virulent under the influence of changing atmo- 
 spheric conditions. It is more likely, however, that the various 
 cosmic changes act with greater energy upon the invaded organisms 
 than upon the invaders. As has already been stated, the more 
 highly developed and delicate the animal organization, the more sen- 
 sitive it is to variations in the surrounding medium. For instance, 
 man is influenced by changes in atmospheric pressure or thermal 
 
96 INFECTIO US DISEASES. 
 
 variations, far more than the microbe. The explanation of "genie 
 epidemique " must, therefore, be sought in the disturbances mani- 
 fested in massed humanity. The appearance, course, more or less 
 extensive ravages, and decline or disappearance of epidemics depend 
 chiefly upon the influence exerted by meteoric, hygienic, and social 
 conditions upon human organisms. 
 
 The insufficiency and laconicism of ancient descriptions make it 
 difficult to compare the diseases of the present time with those of 
 the past. With reference to some of them, however, the course of 
 evolution is not a matter of doubt. For instance, leprosy was very 
 frequent in the thirteenth century, when there were 2000 leprosy 
 houses in France and 19,000 in Europe. At present this disease is 
 localized in a few regions. In France sporadic cases are met with 
 around Marseilles and Nice. 
 
 On the other hand, some diseases have made their appearance at 
 a certain epoch, and do not seem to be destined to disappear in the 
 near future. For example, the eruptive fevers were imparted in the 
 sixth century. Although smallpox existed in China a thousand 
 years before Christ, its occurrence in Europe was not mentioned until 
 the year 570 a.d. by Marius, bishop of Avenches (Switzerland), and 
 in 580 a.d. by Gregory of Tours. Measles, which dates from the 
 same epoch, seems to have definitely settled among us. Scarlet 
 fever was mentioned by Ingrassias in the 'sixteenth century. Finally, 
 sudor anglicus appeared in England for the first time in the fifteenth 
 century and ceased in 1551. The symptoms of the first epidemics, 
 however, were very different from those presented by modern epi- 
 demics, the history of which begins in the eighteenth century (suette 
 picarde, 1718-23). Therefore, some authorities, such as Hecker and 
 Littre, have denied the identity of the two epidemics. 
 
 Passing to modern times, we find cerebrospinal meningitis, which 
 did not appear until the nineteenth century. In 1831 cholera made 
 its first appearance in Europe, and the following year it entered 
 France. Since that epoch it has returned several times, always pre- 
 serving the same clinical characters, but tending more and more to 
 acclimate itself to our countries and to become localized in small 
 endemic foci. 
 
 The symptomatology of infectious diseases has not remained inva- 
 riable. The history of influenza reveals that the malady was for- 
 merly observed in the form of catarrhs and pulmonary localizations. 
 At present it occurs also with nervous symptoms which, in some 
 
ETIOLOQ ? OF INFECTIONS. !>7 
 
 cases, are the predominant or only manifestation , and an 
 For months after apparent recovery. Similar remark are appli< 
 to pneumonia. This infection no longer presente the former fn 
 plain character, lis resolution is far more tedious, and everal 
 after defervescence stetlioscopic signs may be found which embi 
 the physician and lead him to doubl the nature of the pro© 
 
 The causes of all these changes are mostly unknown. A few con- 
 ditions, however, have been determined. 
 
 At nil times it has been noted thai fatal epidemics were preceded 
 by cosmic perturbations, greal variations in pressure and tempera- 
 ture, earthquakes, and volcanic eruptions. At the presenl time we 
 are unable to conceive the mode of action of these cosmic agencies. 
 
 We are a little better acquainted with the influence of social con- 
 ditions. Infectious diseases change in frequency and form parallel 
 to variations in the progress of civilization. During the warlike 
 periods of humanity infections reigned as a result of traumatism, 
 overwork, and crowding. During the periods of naval conquests 
 we transported beyond the seas the maladies of our continent and 
 imported various exotic infections. 
 
 Modern civilization has arrested the course of epidemics, and the 
 advances of therapeutics have diminished their mortality. Vaccina- 
 tions tend to abolish certain diseases, notably variola. 
 
 Some infections, however, persist with obstinate tenacity. Tuber- 
 culosis seems to be on the increase. 
 
 Although hygiene has diminished the frequency of infections, it 
 has been less effective as regards intoxications. The latter become 
 more and more numerous. Alcoholism tends to favor certain infec- 
 tions and to modify clinical types. The advances of civilization as 
 a cause of growing excitation of the nervous system favor the devel- 
 opment of cerebral manifestations, thus modifying clinical types. 
 The pathology of the nineteenth century differs from that of pre- 
 ceding ages and will differ from that of the future. Infections are 
 subject to the general laws of evolution, and, while we are unable to 
 comprehend all the conditions which contribute to modify the clinical 
 characters of diseases, we at least understand that they cannot 
 remain immutable. 
 
CHAPTER IV. 
 
 PATHOGENESIS OF INFECTIONS. 
 
 Role of Microbes in the Development of Infections. Importance of the Number. Vari- 
 ations of Virulence. Exaltation and Attenuation. Selective Harmfulness for 
 Certain Organs or Tissues. Modes of Entrance of Microbes. Importance of the 
 Mode of Entrance with Regard to Gravity and Symptoms of Infection. Modes of 
 Action of Microbes. Discussion of Hypotheses. Role of Microbic Poisons. Study 
 of Putrefaction Poisons and Gastrointestinal Poisons. Autointoxications of Gastro- 
 intestinal Origin. Toxins of Pathogenic Microbes. Local Action and General 
 Manifestations Ascribable to These Toxins. Study of the Principal Toxins Produced 
 by Pathogenic Microbes. The Poisons in the Infected Organism. Toxic Charac- 
 ter of the Blood, Serum, and Urine. Urinary Toxins and Ptomains. 
 
 Role of Microbes in the Development of Infections; Role of 
 Number. An infectious disease expresses the struggle engaged 
 between an animal organism and a microbic agent. In order to 
 understand the evolution of the disease we must study successively 
 those modifications of the organism and of the microbe which favor 
 or hinder the production of morbid phenomena. 
 
 Let us first consider the role of the microbe. It is now known that 
 it is necessary to take into account both the quantity and the quality 
 of pathogenic agents attacking the organism. 
 
 In the beginning of bacteriological studies, when an endeavor was 
 made to differentiate infections from intoxications, it was thought 
 that, contrary to what is true with regard to poisons, quantity was 
 of no importance when the question was one of microbic virus. This 
 was at the time when Davaine showed that one-millionth of a drop 
 of blood derived from an animal infected with anthrax possesses 
 sufficient virulence to cause death. The researches of Chauveau, 
 W. Cheyne, and Bouchard have fully established the importance of 
 quantity. Thus the guinea-pig, of all animals the most susceptible 
 to tuberculosis, does not contract the infection unless eight hundred 
 and twenty bacilli are introduced beneath its skin. With pus cocci 
 far greater numbers are requisite. 
 
 Operating with proteus vulgaris, Watson Cheyne discovered that 
 6,000,000 of microbes injected beneath the skin do not produce any 
 lesion; 8,000,000 cause the formation of an abscess; 56,000,000 give 
 
I'A TH0QENESI8 OF INFECTIONS. 
 
 rise to a phlegmon to which the animal 3uccum.bc within fi 
 weeks; 225,000,000 must be injected in order to cau e death within 
 twenty-four or thirty hours. Experimenting with staphylocoi 
 upon rabbits, he found thai 250,000,000 microbes are required to 
 produce an abscess and to cause death, one milliard (1,000,000,000 , 
 
 We have obtained quite similar results by inoculating into guinea- 
 pigs cultures of staphylococcus aureus obtained from a phlegmon 
 consecutive to erysipelas. An injection of 0.2c.cm. produced a cir- 
 cumscribed abscess; ().(> cciii. caused edema, followed by a patch of 
 sphacelus; with exfoliation of the slough the connective tissue and 
 subjacent muscles were found to be necrotic. Finally, with 1 c.cm. 
 an enormous invading edema was obtained which ended fatally in 
 four or five days. 
 
 These facts are interesting because they show that inoculation of 
 the same microbic cultures into the same region in animals of the same 
 species gives rise to manifestations which vary in gravity and nature 
 according to the dosage. The experimenter is thus able to produce, 
 at will, abscess, gangrene, or fatal edema. 
 
 In all these experiments the microbes were injected beneath the 
 skin. By varying the mode of introduction, different results are 
 obtained. To produce suppuration with staphylococcus aureus it 
 was necessary in the researches of Herman to inject 4 c.cm. to 5 c.cm. 
 of the culture into the peritoneal cavity, 0.75 c.cm. to 1 c.cm. beneath 
 the skin, 0.25 c.cm. into the pleural cavity or arachnoid space, 
 0.5 c.cm. into the veins, and 0.0001 c.cm. into the anterior chamber 
 of the eye. The anterior chamber of the eye, therefore, is the most 
 poorly protected part of the organism. The same is also demon- 
 strated by the study of symptomatic anthrax. This virus, which is 
 inoffensive to rabbits when injected hypodermically, causes speedy 
 death when introduced into the anterior chamber of the eye. 
 
 Variations in the Virulence of Microbes. A fact of prime importance 
 dominates the history of all infections, viz., the virulence of microbes 
 is not fixed and unchangeable. It is modified by a vast number of 
 circumstances of which several have been clearly determined. 
 
 As exaltation may be considered an adaptation to new biological 
 conditions, it is conceivable that a microbe can be habituated to the 
 living medium and develop more and more easily therein. Inocula- 
 tions in series offer the best means of increasing pathogenic potency. 
 On the other hand, cultivation in inert media is the surest method 
 for diminishing pathogenic potency, and the more the culture medium 
 
100 INFECTIOUS DISEASES. 
 
 differs from the organic medium the more speedily is the virus 
 attenuated. This weakening is more rapidly effected in mineral 
 solutions than in bouillon, and more readily in bouillon than in 
 blood serum or in defibrinated blood. 
 
 It is to be noted that a microbe exalted for one animal species is 
 not necessarily so for others. We have studied a specimen of anthrax 
 which, after successive passages through rabbits, had become, con- 
 trary to the rule, far more virulent for this animal than for the 
 guinea-pig. In this connection we may cite the experiments of 
 Pasteur, showing that the virus of hydrophobia is attenuated when 
 inoculated into monkeys, as is evident from the increase in the period 
 of incubation. 
 
 These results are not merely of theoretical interest. They explain 
 certain facts which, at first, may seem incomprehensible. 
 
 In fact, under the habitual conditions of life, we see that viruses, 
 by passage through the organisms of different animals, undergo such 
 modifications as to puzzle the observer as to their origin. Thus, it 
 is now demonstrated that tuberculosis is produced in all animals by 
 a single bacillary species. The microbes have suffered changes, how- 
 ever, according as they have invaded mammalia or birds, thus con- 
 stituting two varieties which have appeared to some observers as 
 two different species. The bacillus exalted for birds is attenuated 
 for mammalia, and vice versa. 
 
 The knowledge of these facts shows that inoculation into animals 
 does not always yield results responding to the previsions of clinical 
 observation. We cannot establish a diagnosis for man upon experi- 
 mental results. Virulence being a contingent property, depending 
 rather upon the invaded organism, it is conceivable that it should 
 differ with each being under consideration. 
 
 Selective Injuriousness of Pathogenic Agents. Some of the patho- 
 genic agents manifest an affinity for a certain organ or tissue in which 
 they settle, and manifest no tendency to invade other parts. They 
 are even incapable, at times, of emigrating from the organic territory 
 to which they are habituated. Thus the microbe of mumps fixes 
 itself in certain glands; the cholera vibrio multiplies exclusively in 
 the intestine ; the agent of hydrophobia invades the nervous system. 
 Some specific bacteria, however, are apt to colonize more or less 
 everywhere. Such, for instance, are the bacillus of glanders, the 
 tubercle bacillus, and the agent of syphilis. 
 
 On the other hand, the non-specific bacteria are all capable of 
 
PATHOGENESIS OF INFECTIONS. ]ol 
 
 developing in the most dissimilar pari of the organism. There is 
 
 no tissue or ;in organ which cannot be invaded by i lie staphylococ 
 streptococcus, pneumococcus, or colon bacillu . 
 
 Even these common agents, however, are in some degree capable 
 of education, and acquire a special aptitude to live in :i certain ti 
 They become used to the biological conditions of thai pari of the 
 organism, and no longer manifest any inclination to invade others. 
 This fact was illustrated in a case of acute ascending paralysis which 
 i In- author studied with Dr. .Io-imV The manifestations were due 
 to a pneumococcus which, when inoculated into animals, prod 
 spinal symptoms. This microbe, then, behaved as if it bad acquired 
 a sort of selective harmfulness for the nervous tissues by virl 
 its first passage through the spinal cord of our patient. 
 
 Our idea was taken up and developed by Drs. Bezancon and 
 Labbe, 2 who collected a certain number of facts showing thai 
 microbes obtained from an organic lesion when introduced into 
 animals localize themselves in that part which was attacked in 
 the human subject. Thus, Dreschfeld produced endocarditis in 
 rabbits which were inoculated with a streptococcus derived from 
 an infectious endocarditis. 
 
 These facts prove that microbes may acquire the habit of colon- 
 izing in a certain organ or tissue in preference to others. It may 
 now be asked why a microbe, for the first time, localizes itself at a 
 certain point of the economy. Several conditions may intervene. 
 One of these is the mode of entrance of the pathogenic agent. 
 
 Modes of Entrance of Infectious Agents. Certain microbes 
 possess such a high degree of virulence that their introduction into 
 the organism is invariably followed by the development of a fatal 
 disease. No matter what the mode of introduction may be, the 
 result is the same. Such, for instance, is the case observed when 
 chicken cholera is inoculated into the rabbit. This fact, however, is 
 exceptional. In most cases infection is modified according to the 
 channel by which the virus enters. 
 
 The usual modes of entrance of morbific germs are four: the skin 
 and the subcutaneous cellular tissue, the respiratory passages, the 
 alimentary canal, and the genito-urinary apparatus. 
 
 1 Roger et Josue. Un cas de paralysie ascendaute aigue. Presse medicals. Ju 2 i 
 1898. 
 
 2 Bezancon and Labbe. Role de l'aecutumance dan? la determination des lex 
 lions microbiennes. Presse meclieale. March 7. 1900. 
 
102 INFECTIOUS DISEASES. 
 
 Infections of Cutaneous Origin. In this connection, the first ques- 
 tion to be asked is whether pathogenic agents are capable of invading 
 the organism through the unbroken skin. As a rule, they are not. 
 The rule is not, however, without exceptions, especially as regards 
 the mucous membranes. Let us first see what occurs with the skin. 
 
 Ancient observers admitted that viruses could penetrate through 
 the intact epidermis. The fact seems to be real with regard to 
 certain pus cocci, as is demonstrated by the frequencjr of small 
 pustules upon the back of the hands of anatomists. The microbes 
 are undoubtedly introduced through the sebaceous glands. Roth, 
 by rubbing the skin of guinea-pigs with a mixture of fat and a 
 bacteria culture, was able to produce abscesses. When experimenting 
 with anthrax he witnessed the production of a local edema which 
 in some cases proved fatal. No result, how r ever, was seen when the 
 culture was simply deposited upon the skin without any friction. 
 By similar procedures, Babes succeeded in inoculating glanders into 
 guinea-pigs through the healthy skin. 
 
 When infection occurs in the skin the lesion often remains limited 
 to the spot. This is what happened in Roth's experiments with 
 the anthrax bacillus. The same is demonstrated by clinical obser- 
 vation. Lupus and anatomical tubercles manifest hardly any ten- 
 dency to generalization. The fact may be due to the special struc- 
 ture of the skin. It may also be explained by the temperature of 
 the skin, which is too low to favor active vegetation of the microbic 
 agent. 
 
 Subcutaneous Inoculations. In most cases the virus is deposited 
 beneath the skm, either in the cellular tissue, or even more deeply 
 in the muscles and nerves. 
 
 With the same virus the results may differ according to the point 
 of subcutaneous inoculation. Thus the regions where the connective 
 tissue is dense are not very favorable for the propagation of microbes. 
 If a very energetic virus, such as that of symptomatic anthrax or of 
 gaseous gangrene, is inoculated into the tip of the tail or the ear, 
 only a local lesion capable of causing the loss of a part of the organ 
 results, but ending in recovery. The density of the cellular tissue 
 and the low temperature of the region hinder the vegetation of the 
 microbes and insure survival of the animal, which would certainly 
 perish if the inoculation were practised at some other point. 
 
 The results of inoculation also vary according to the depth of the 
 wound. In this respect nothing is more interesting than the study 
 
PA THOQENESIS OF INFECTIONS. 
 
 of hydrophobia. Helman discovered thai the adipoa offers 
 
 an unfavorable channel of absorption for the hydrophobic virus. 
 Fat dogs, therefore, resist hypodermic inoculation, while the young 
 and thin ones mostly perish. When thevirusu introduced into the 
 subcutaneous cellular tissue of mbbiis, 7o per ceni . of the inoculated 
 animals die. If the injection is made into a muscle, the mortality 
 rises to <s> r ) per cent. If sectioned musHe- are operated upon, and 
 the virus is introduced between the muscular fibres, all the animals 
 succumb. 
 
 The deductions which may be drawn from these experiments are 
 .self-evident. The great danger attending deep wounds is in part 
 due to the introduction of the virus into the subcutaneous mu 
 and nerve fibres. Numerous experiments have shown that the 
 hydrophobia virus follows the nerve fibres in order to reach the 
 nerve centres, where its localization gives rise to clinical mai 
 tations of the most fearful character. Hence the more richly the 
 wounded part is supplied with nerves the more certain is contam- 
 ination and the shorter the period of incubation. 
 
 Infections through the Mucous Membranes. The mucous membranes 
 are more easily penetrated by microbes than the skin. The patho- 
 genic agents often leave no trace of their passage or, after giving 
 rise to some slight and curable lesion, invade the neighboring 
 lymphatic ganglia. By depositing tuberculous sputum in the lower 
 conjunctival cul-de-sac, without any traumatism of the mucous 
 membrane, Cornet observed no more than a little redness at the 
 point of inoculation. The cervical glands, however, became caseated, 
 and microscopic examination revealed in them the presence of 
 numerous tubercle bacilli. He operated upon the mucous mem- 
 branes of the nose, gums, penis, and vagina with similar results. 
 
 Infection through the Respiratory Passages. The respiratory tract 
 is believed to be a frequent channel of contamination. Many authors 
 assert that the germs of eruptive fevers, especially those of measles 
 and variola, are introduced by this route. 
 
 On the other hand, it has been remarked that while infection is 
 grave when it occurs spontaneously, it is generally mild when it 
 originates by subcutaneous inoculation. This is demonstrated by 
 the practice of variolization. 
 
 In studying the respiratory mode of entrance, authors have ck - 
 particularly the bacillus anthracis. Flugge and Wyssokowicz asserted 
 that the bacillus could not pass through the intact lung. Such 
 
104 INFECTIOUS DISEASES. 
 
 conclusion can no longer be accepted in view of the researches of 
 Buchner. Muskalbluth, and Enderlein. These authors made numerous 
 experiments, consisting in the injection of the virus directly into the 
 trachea, or in- causing it to be breathed in the shape of dried powder. 
 Most of the animals — rats and guinea-pigs — died. 
 
 Buchner produced a general infection, without any pulmonary 
 alteration, by causing animals to inhale anthrax spores. By employ- 
 ing the bacilli themselves he often observed red hepatization and, 
 in these cases, the animals survived. This result is explained by the 
 fact that the adult microbes, which are comparatively weak, succumb 
 and transude an irritating substance, while the spores give birth to 
 vigorous bacilli of great resistance. The local lesion is, therefore, 
 the result of the organic resistance, though this is not always suffi- 
 cient to prevent infection. This is further illustrated by the study 
 of the pneumococcus. If this microbe is introduced into the trachea 
 of an animal very sensitive to its action, such as the rat or the rabbit, 
 no pulmonary lesion is obtained, but death supervenes as the result 
 of a general infection — that is, a veritable septicemia. If a more 
 resistant animal is experimented upon, the dog, for instance, the 
 result is a fibrinous pneumonia. The same is true with regard to 
 man. The pneumococcus is present in the oral cavity of many 
 healthy persons. When a disturbing influence diminishes the or- 
 ganic resistance a pneumonia is produced expressing the reaction 
 of the individual against the pathogenic agent. The same remark 
 is also applicable to diphtheria. 
 
 In the majority of cases the bacilli of tuberculosis invade the organ- 
 ism through the respiratory organs. The experiments of Tappeiner 
 demonstrate that dogs, which are quite resistant to tuberculosis, 
 easily contract this malady when they inhale dried and pulverized 
 sputa. The local lesion, however, may be lacking or promptly 
 repaired. The bacilli pass through the lung without leaving any 
 lasting trace of their passage, and take up their abode in other parts 
 of the organism. They may cause a general infection or be arrested 
 in the mediastinal ganglia. The latter event is frequently observed 
 in children who are so often victims of seemingty primary tracheo- 
 bronchial adenopathies. 
 
 It is not to be assumed, however, that the respiratory passages 
 represent a door open to all infections. The bacilli of symptomatic 
 anthrax and of gaseous gangrene may be introduced into the trachea 
 with impunity. They give rise to no disturbance, for the reason, 
 
PATHOGENESIS OF INFECTIONS. 106 
 
 perhaps, that these agents are anaerobic, [t must further be remem- 
 bered that in this organ, as id the rest of the economy . important 
 means of defense, including phagocytosis, exi t. 
 
 Infection by the Alimentary Canal. Under QOrmal eondition- the 
 
 digestive tract contains a prodigious quantity of microbes, of which 
 several are pathogenic. Owing, however, to the numerous modes of 
 protection with which this canal is endowed, the presence of the 
 microbes gives rise to no disturbance. Neverl heless, infection is pos- 
 sible, though here it is more didieiili than through the respiri 
 passages. While the inhalation of the bacillus anthracis kills most 
 of the animals — rats or guinea-pigs— its ingestion is, as a rule, well 
 resisted. 
 
 The alimentary canal may be the starting point of a great num- 
 ber of infectious diseases. It will suffice to mention typhoid fever, 
 dysentery, and cholera. 
 
 Tuberculous lesions are also frequently observed in the digestive 
 canal and are generally secondary to deglutition of sputa. They 
 may, however, be primary, as a result of ingestion of contaminated 
 food and, particularly, milk drawn from cows affected with mam- 
 mary tuberculosis. 
 
 Tuberculosis of intestinal origin may appear in two different forms: 
 1. The localizations are sometimes found in the canal and the mode 
 of entrance is readily recognized. 2. At other times no intestinal 
 lesion is discoverable, since the bacilli have passed onward to colonize 
 in the mesenteric ganglia, peritoneum, or even the lungs. 
 
 Of all the microbes normally inhabiting the intestine the most 
 interesting is undoubtedly the bacillus coli communis. The study 
 of the diseases which it is capable of producing is the finest illustra- 
 tion of the surprising modifications undergone by a microbe. An 
 innocent guest in most human subjects, under influences as yet 
 vaguely recognized, it may acquire noxious properties and give rise 
 to the most varied intestinal disturbances — simple diarrhea, dysen- 
 teriform diarrhea, or some form of cholera. It may even leave the 
 intestine and produce either septicemias or bronchopneumonias: or, 
 by ascending the biliary passages, induce a suppurating angiocholitis. 
 
 Migration may occur when there is some obstacle to the course of 
 fecal matters. Artificial occlusion of the rectum suffices to cause 
 bacteria to pass into the general circulation (Possner and Lewim. 
 The same phenomenon is observed in the course of certain infections 
 and intoxications. According to Chvostek and Egger, after a mala- 
 
106 INFECTIOUS DISEASES. 
 
 rial paroxysm and after the injection of tuberculin, various microbes 
 can be found in the urine, particularly the colon bacillus, which 
 probably comes from the intestine. The researches of Beco, Wurtz, 
 and Hudelo demonstrate that poisoning by tartar emetic, canthari- 
 din or alcohol likewise favors penetration of bacilli. Authors have 
 thus been led to attribute to infection a role in the origin of alcoholic 
 cirrhosis. 
 
 Infection by the Genito-urinary Organs. Under normal conditions 
 microbes do not pass beyond the navicular fossa. They may often, 
 however, invade the rest of the urethra after catheterization or after 
 sexual intercourse. In the latter instance, several infections may 
 be transmitted, from gonorrhea to tuberculosis. The infection may 
 pass from the urethra into the bladder, but scarcely ever beyond 
 that point. As has been established by Albarran and Halle, nu- 
 merous microbes are very frequently found in the bladder. Only 
 one, however, the bacillus coli, is capable of advancing to the renal 
 pelvis and kidneys. It is interesting to note that this microbe 
 manifests the same tendency to ascend to the liver along the excre- 
 tory passages and contrary to the current of the bile. Angiocholitis 
 and suppurative nephritis represent two perfectly analogous pro- 
 cesses. 
 
 In women protection against microbes is quite efficacious. Even 
 after parturition, infections of genital origin are difficult. Experi- 
 ments have shown that the uterus of a puerperal woman possesses 
 a special resistance. Certain microbes, however, notably the strep- 
 tococcus, can invade it, producing one of the forms of puerperal fever. 
 
 Infection by the Organs of Sense, Serous Membranes, and the Nervous 
 System. It has ahead}'' been stated that the conjunctiva may 
 serve as a channel of entrance, but the anterior chamber especially 
 offers an important route of introduction, at least from an experi- 
 mental standpoint. Thus, for instance, hydrophobia as surely de- 
 velops when the virus is deposited at this point as when it is intro- 
 duced into the nervous system. Cohnheim and Baumgarten have 
 discovered that this is a very certain channel for the introduction 
 of tuberculosis. 
 
 The serous membranes are not a route habitually open to infec- 
 tions, except in cases of traumatism. Experimenters frequently 
 employ it for the introduction of microbes. At all events, the results 
 are similar to those obtained with inoculations into the mucous 
 membranes. In some instances the animal resists ; in others a gen- 
 
PATHOGENESIS OF INFECTIONS. ]07 
 
 era! infection is prod need without any lesion al the poinl of injection. 
 At oilier limes a local lesion is caused which may or may nol be 
 followed by general infection. 
 
 Lastly, another channel for contamination is the nerv< tern. 
 
 The agent of hydrophobia propagates through the nei i both 
 
 clinical observation and experimental researches have demonstrated. 
 In this way the virus reaches the nerve centres. It is conceivable, 
 therefore, that the nearer the affected nerve U to the spinal bulb 
 the shorter the period of incubation, and, furthermore, the firsl mani- 
 festations will vary with the region primarily contaminated. 
 
 Infection by the Vascular System. Whatever the route by which 
 
 microbes arc introduced into the organism, they either remain al 
 the point where they are primarily deposited or invade the organism. 
 In the former case they may be speedily destroyed or give rise to 
 the formation of a local lesion, which often represents a means of 
 defense opposed by the organism. However, the microbes multiply- 
 ing at the point of the lesion al times secrete extremely active toxic- 
 substances, and in this manner give rise, not to an infection, bul to 
 a more or less serious intoxication which is at limes fatal. This is 
 what occurs in gaseous gangrene, diphtheria, and cholera. ' ! 
 maladies should, therefore, be considered as bacteriotoxemias. 
 
 When infection is generalized, whether a local lesion is present or 
 not, the microbes penetrate by the bloodvessels or the lymphatic 
 channels. In the latter case they are first arrested by the glands, 
 the hypertrophy of which testifies sufficiently as to their incr< - 
 activity. The process may stop here or may pass beyond the barrier 
 opposed by the glands and spread in the blood. 
 
 Under natural conditions the blood is almost always secondarily 
 invaded. Direct introduction into the circulation occurs only in the 
 fetus, since the pathogenic agents cannot reach it otherwise than 
 by the sole point of contact which it has with the external world 
 — that is, the umbilical vessels. Infection then assumes a special 
 aspect imposed by its localizations. It is thus conceivable that the 
 liver should be profoundly altered in inherited syphilis and that the 
 various stages should not be separated, as in the adult. There is 
 generalization from the first: hence, the absence of primary lesions 
 and confusion of secondary and tertiary stae 3. 
 
 Whether directly introduced into the veins or secondarily invading 
 the circulatory system, microbes do not remain in the blood. They 
 rapidly leave this unfavorable medium and take refuge in the tissues 
 
108 ISFECTIOUS DISEASES. 
 
 and organs. They do not, however, distribute themselves equally 
 in all the tissues, nor do they affect all the organs in the same maimer. 
 The results vary according to the species or variety under observa- 
 tion. If a tissue is already altered, whether by traumatism or pre- 
 vious disease, the microbes will preferably settle in those parts of 
 lessened resistance. It is, therefore, possible, in experimental re- 
 searches, to cause a pathogenic agent to colonize at this or that 
 point of the organism, and thus create, at will, nephrites, endocar- 
 dites, osteomyelites, and infectious arthrites. 
 
 Mode of Action of Pathogenic Microbes. The causes favorable 
 to infection having been described, it remains to study in what 
 manner microbic development is followed by morbid disturb- 
 ances. 
 
 Several theories have been advanced. In the first, a mechanical 
 theory, it is assumed that the microbes act simply like foreign bodies; 
 by obstructing the capillaries they hinder the functions of the organs. 
 This conception is hardly deserving of discussion, especially in view 
 of the fact that the microbes often remain localized in some organ 
 or tissue, or at some point of very limited extent, as in the case of 
 diphtheria, tetanus, and symptomatic anthrax. 
 
 In the second theory it is assumed that there is a struggle for life. 
 It is supposed that the microbes and the cells of the organism vie 
 with each other for the possession of the alimentary materials and 
 oxygen carried by the blood. When the question is one of a microbe 
 like the diphtheria bacillus, which lives upon the surface of a mucous 
 membrane, or of an anaerobic agent, such as the bacillus of tetanus, 
 the oxygen of the blood is not needed for the development of the 
 pathogenic agent. As to the use of nutritive materials, how much 
 of them can the microbes consume? We have no information con- 
 cerning this point. However, notwithstanding their active multi- 
 plication, microbes weigh too little to give strength to the opinion 
 that their development starves the economy. The problem is more 
 complex. In order to nourish itself, every being is forced to secrete 
 ferments which transform or modify the alimentary substances. 
 Miorobes are subject to this law and produce amylolytic, inversive, 
 and proteolytic ferments. These ferments give rise to substances 
 which may serve their nutrition, but may prove harmful to the 
 invaded organism. As in every living cell a double process — assimi- 
 lation and disassimilation — goes on in the interior of microbes. The 
 products of bacterial disassimilation, useless to the microbes, are 
 
PATHOGENESIS OF INFECTIONS. ]u:i 
 
 rejected into the interstitial plasma and into the blood, and repre- 
 sent other noxious substance 
 
 Moreover, the substances of which the tnicrobic protoplasm i 
 composed are not harmless. This also if the application of a general 
 law. The extracts of all tissues give rise to morbid phenomena when 
 injected into animals. These manifestations, which occur even when 
 animals of the same species are operated upon, are much more 
 marked when different species are employed. This is equally true 
 with regard to bacteria. Their protoplasm contain toj ic ubstances 
 which may readily diffuse after their death, or perhaps even during 
 life. 
 
 We conclude, therefore, thai infect ious agent - exerl only a mechan- 
 ical influence of secondary importance. They give rise to nervous 
 reactions, not by crowding the tissues, hut through the agency of 
 noxious substances which they produce and pas- into the blood. As 
 already stated, infection is a chapter of the history of intoxications. 
 
 Microbic Poisons. 
 
 Putrid Poisons. Before the discovery of pathogenic microbes, 
 
 at an epoch when the nature of putrefactive agents was not even 
 suspected, interesting results had already been obtained in the study 
 of poisons produced by fermentations. 
 
 At the end of the eighteenth century Seybert 1 demonstrated that 
 the putrefaction of pus, serum, and infusions of meat developed in 
 these fluids a high degree of pathogenic power. He pointed out . for 
 instance, that the intravenous injection of 20 c.cm. of putrefied serum 
 into a dog produced vomiting and convulsions, ending in death within 
 a few hours. 
 
 The question was taken up by Gaspard, 2 physician at St. Etienne. 
 who pursued a series of very remarkable researches, the result- of 
 which were confirmed and completed by Magendie, Virchow, Stich, 
 and, above all, by Panum, who, in 1856. isolated a poison the effects 
 of which were comparable to those of the toxic substances above 
 mentioned. 
 
 It is not sufficient, however, to point out the toxicity of putrid 
 substances. The very element upon which their noxious action 
 
 1 Seybert. Ueber die FauLoiss in Blute an lebenden thierischen Korper. Berlin. 
 
 2 Gaspard. Mdmoire physiologique sur les maladies purulentes et putrides. Journal 
 
 de la phys.. 1S22. 1S'24. 
 
110 iyFECTIOUS DISEASES. 
 
 depends must be discovered. The bodies originated during the 
 process of putrefaction are excessively numerous and, moreover, vary 
 according as the substances are exposed to the open air or kept in 
 closed vessels'; according to the time putrefaction has lasted; accord- 
 ing to the nature of the materials undergoing the process, etc. The 
 following table, nevertheless, presents the principal substances: 
 
 \ hydrogen, sulphuretted hydrogen, phosphor- 
 Gas ated hydrogen, protocarbonated hydrogen, 
 ammonia, sulphohydrate of ammonia. 
 carbonic acid, 
 phosphorated gas, vaguely known (phosphins). 
 
 formic (traces). 
 r volatile gases . . \ acetic. 
 
 Acids 
 
 butyric (very abundant), 
 valeric. 
 
 {acrylic, 
 crotonic. 
 palmitic, 
 oleic, 
 glycolic. 
 [ polyatomic . . J lactic, 
 alic. 
 
 rgiy 
 
 J lac 
 
 j OXE 
 
 *- S11P 
 
 succinic, 
 findol. 
 | phenol. 
 
 Aromatic substances . J skato1 - 
 
 J paracresol, orthocresol. 
 
 r phenylacetic, pyroxylphe- 
 [_ acids .... J nylacetic. 
 
 j phenylpropionic, paroxyl- 
 ' phenylpropionic. 
 Albuminoid substances -f albuminates. 
 I peptones. 
 
 (leucin, leucein. 
 tvrosin. 
 xanthin, hypoxanthin. 
 , complex amido bodies. 
 Organic bases . . . J methylamin, trimethylamin etc. 
 \ ethylendiamm, amylamm, etc. 
 I alkaloids or ptomains. 
 
 Finally, the residues of putrefaction are rich in earthy and ammo- 
 niacal salts, in fats, and often in nitrates. 
 
 So far as the gases are concerned, it is now known that they are 
 not responsible for the toxicity of putrid matters. The same is true 
 of fatty acids, aromatic substances, and amido bodies. There remain 
 the albuminoids and the bases. According to Panum, toxicity must 
 be attributed to the former group. Later came a series of very 
 notable contributions, due to Nencki, Maas, and, above all, Brieger, 
 who thoroughly studied the bases of putrefaction. Selmi 1 called 
 them ptomains in order to indicate their cadaveric origin. He 
 recognized that these ptomains are very numerous; that some are 
 inoffensive and others toxic; that they resemble vegetable alkaloids; 
 
 1 Selmi. Ptomain ad alcaloide cadaverici. Bologna, 1881. 
 
PATHOGENESIS OF INFECTIONS. Ill 
 
 that they cause pupillary disturbances, cardiac irregularity . nar- 
 cosis or convulsions, and produce death by arresl oi the hearl in 
 systole. 
 We cannot sum up all the works published on this interesting 
 
 subject. Prof, (lautier, who was first to point out the existence ol 
 animal alkaioids, has several times returned to their study. Bri< 
 took up the complete study and reported a number of very remark- 
 able facts. He assumes thai al the beginning of all putrefaction, 
 lecithin (C 44 H 20 NPO 9 ) is broken up into its components, and the 
 oxyethylic base, cholin (C 6 H 16 N0 2 ), a substance of little toxicity, 
 gives rise to a vinylic base, nervin (C 5 H 18 NO), a highly toxic body 
 which is produced simply by subtraction of one molecule of water. 
 The transformation of lecithin is readily accounted for by the 
 great fragility of its highly complex molecule. It is, however, diffi- 
 cult to say whether the transformation of cholin is due to the 
 reducing properties of the tissues which acquire so greal an energy 
 immediately after death, or whether it is already the work of micro- 
 organisms. 
 
 However that may be, here is a highly toxic base originated al the 
 beginning of putrefaction. Brieger s researches have established 
 that nervin is particularly active for the cat, which is killed by a few 
 milligrams of it, while as much as four centigrams are required to 
 kill a rabbit. Aside from nervin, there are two other bases: neu- 
 ridin (C 5 H H N,), which is not toxic, and methylguanidin (Brieger . 
 which is tetanizing. There is also parvolin (C 9 H 13 N), found by 
 Gautier and Etard in the putrid flesh of the horse: collidin, hydro- 
 collidin, and two other bases isolated by Dr. Pouchet and having 
 the formulae: one, C 7 H IS N 2 0„; the other, C 5 H 12 N 2 4 . These bodies 
 are very toxic. Harmless bases, such as corindin (C^H^N), are also 
 encountered. On the whole, the convulsifying alkaloids are dom- 
 inant. 
 
 Brieger has established that the alkaloids produced in the human 
 cadaver vary with the time elapsed since the moment of death. The 
 first one is cholin, which appears as early as the first or second day 
 and disappears toward the seventh day. On the third day neuridin 
 is produced, which disappears toward the end of the second week. 
 At the same time cadaverin may be isolated, which increases with 
 the progress of putrefaction: then, toward the fourth day. appear 
 
 1 Brieger. Untersuchungen iiber Ptomaine (3 pamphlets'). Berlin. L885-S 
 
112 INFECTIOUS DISEASES. 
 
 putrescin, which is very abundant toward the fifteenth day, and 
 saprin. These bases are not all toxic: cholin alone, when injected 
 in high doses, produces a few symptoms resembling those provoked 
 by muscarine 
 
 The truly toxic substances appear toward the seventh clay. At 
 this stage, aside from trimethylamin, which is of little toxicity, two 
 venomous liases are produced, of which considerable quantities may 
 be collected toward the fifteenth day. One, the less active, causes 
 only alvine evacuations; the other, mydalein, the chemical formula 
 of which has not yet been determined, is extremely powerful. 
 
 When injected into guinea-pigs and rabbits, mydalein causes sali- 
 vation and lacrymation. The pupils dilate, the ears are congested, 
 and the rectal temperature is raised 1.8° to 3.6° F. (1° to 2° C). 
 If the dose reaches five milligrams in the guinea-pig, profuse diar- 
 rhea, exophthalmos, and then paralysis are observed; respiration 
 becomes difficult, the temperature falls, and death supervenes, the 
 heart being arrested in diastole. 
 
 Ehrenberg has discovered several bases hi decayed fish, notably 
 cholin, neuriclin, methylamin, and dimethylamin. The most impor- 
 tant body, however, is ptomatropin of v. Aurep, of which two 
 milligrams cause, in a rabbit, mydriasis, convulsions, and death by 
 arrest of the heart. 
 
 Neuridin and trimethylamin are likewise encountered in putrid 
 milk and cheese ; also a base discovered by Vaughan and designated 
 tyrotoxin. 
 
 As has already been stated, ptomains differ notably according to 
 the time at which the products of putrefaction are studied. Some 
 appear and later disappear, to be succeeded by others. The chemical 
 researches which have revealed these facts, however interesting they 
 may be, ought to have been completed by bacteriological studies. 
 It is, in fact, a question whether these diverse ptomains are produced 
 during the various phases of the life of the same microbes, or whether 
 their successive appearance and disappearance depend upon different 
 microbes which destroy or transform the substances already produced 
 by their predecessors. 
 
 Although we do not know exactly the role of ferments in the 
 genesis of ptomains, we are better acquainted with the influence 
 exerted by the media. It is known that certain bases are encoun- 
 tered in all putrefactions, for instance, neuridin, while neurin is found 
 only in the putrefying flesh of mammalia and muscarin in that of 
 
PA TH0QENE8I8 OF INFECTIONS. 
 
 n:; 
 
 decayed fish. Likewise, gadinin, e1 hylenediamin, and I rimel bylamin 
 are formed at the expense of the flei h of fish. Finally, dimethylamin 
 has thus far been encountered only in the putrefaction of {."'him or 
 of yeast. 
 
 Kostiurinc and Krainsky very justly remark tlial the toxicity of 
 the products of pni refaction is in direcl ratio to the chemical com- 
 plexity of the substances undergoing putrefaction. More poison 
 is yielded by meat- than by bouillon, and more by bouillon than by 
 saline solutions. Toxins are most, abundant from the fifth to the 
 thirtieth day. Furthermore, toxins insoluble in alcohol arc more 
 active than those soluble in this fluid. This last fact clearly shows 
 the importance of non-alkaloidal poisons. 
 
 There is no doubt that whatever cause hinders or favors the devel- 
 opment of microbes also hinders or favors the development of putrid 
 poisons. It will suffice, in this respect, to recall the influence of heat 
 and electricity. As to the role played by oxygen, opinion is divided. 
 An important fact established by Kijanisin has not, perhaps, been 
 sufficiently considered. According to this author, a greater amount 
 of ptomains are produced in contact with air than when the process 
 of putrefaction takes place without air. But the ptomains are then 
 less toxic and less stable; they, therefore, rapidly disappear. 
 
 All the principal ptomains actually known are presented in the 
 table below, following Prof. Gautier's classification: 
 
 
 f Bocklisch, 
 1 Wurtz, 
 
 Decayed fish, 
 
 Xon-toxic. 
 
 Methylamin, CH 6 N, 
 
 Normal blood, 
 
 " 
 
 Dimethylamin, C 2 H 7 N, 
 
 Brieger, 
 
 Putrid yeast, 
 
 " 
 
 Trimethylamin, C 3 H 9 , 
 
 Ibid. 
 
 Decayed fish, 
 
 Convulsions. 
 
 Triethylamin, C B H 1S N, 
 
 Ibid. 
 
 Ibid.' 
 
 " 
 
 Propylamin, C 3 H 9 N, 
 
 Ibid. 
 
 Putrid gelatin, 
 
 " 
 
 Rutylamin, C H a N, 
 
 Gautier and 
 
 Cod-liver oil, 
 
 Stupefying and convulsi- 
 
 
 Mourgues, 
 
 
 fying poison. 
 
 Isoamylamin, C 6 A 13 N, 
 
 Miiller and 
 
 Putrid yeast, 
 
 Stupefying and convulsi- 
 
 
 Hesse, 
 
 
 fying poison. 
 
 Amylamin, C 5 H 13 N, 
 
 Gautier and 
 Mourgues, 
 
 Cod-liver oil, 
 
 Polyuria: convulsions. 
 
 Hexylamin, C 6 H 1S N, 
 
 Ibid. 
 
 Ibid. 
 
 tt n 
 
 
 Hesse, 
 
 Putrid yeast, 
 
 " " 
 
 
 
 f Fresh brain ; 
 
 Xon-toxic. 
 
 Neuridin, C 5 H H N 2 , 
 
 Brieger, 
 
 ■[ all putrefac- 
 l tions, 
 
 Ibid. 
 
 Saprin, C 5 H l4 N 2 , 
 
 Ibid. 
 
 Cadavers, 
 
 Ibid. 
 
 
 f Brieger, 
 
 Cadavers, 
 
 Ibid. 
 
 Cadaverin, C 5 H U N 2 , 
 
 -j Bocklisch. 
 
 Decayed fish. 
 
 Ibid. 
 
 
 f Brieger, 
 
 Cadavers. 
 
 Local action, inflamma- 
 tion necrosis. 
 
 Putrescin, C 4 H, 2 N 2 , 
 
 Bocklisch. 
 
 Herring. 
 
 Local action, inflamma- 
 tion necrosis. 
 
 Ethylenediamin. CJT.,X" ; . 
 
 Brieger. 
 
 Putrid codfish. 
 
 Nasal flux and mydriasis 
 
 dyspnea and death. 
 
 Methylguanidin, C 2 H T X :! . 
 
 Ibid. 
 
 Decayed fish, 
 
 Excitation, then paral- 
 ysis of the nervous sys- 
 tem. 
 
114 
 
 INFECTIOUS DISEASES. 
 
 Nevrin, C 5 H 13 XO. 
 
 Ibid. 
 
 Tainted meat, 
 
 Myosis; salivation; paral- 
 ysis; death. Atrophy 
 (Carvello). 
 
 Cholin, C 5 lI i; ,NO : , 
 
 Ibid. 
 
 Ibid. 
 
 Like muscarin, but action 
 slight. 
 
 Muscarin, C 5 H 15 X03, 
 
 Ibid. 
 
 Putrid codfish, 
 
 Lacrymation, salivation, 
 convulsions. 
 
 Mydotoxin, C„H 13 X0 2 , 
 
 Ibid. 
 
 Cadavers, 
 
 Lacrymation, salivation 
 convulsions. 
 
 Mvdin, CgHnNOa 
 
 Ibid. 
 
 Ibid. 
 
 Xon-toxic. 
 
 Gadinin, C 7 H 16 X6 2 , 
 
 Ibid. 
 
 Decayed fish, 
 
 " 
 
 Methylgadiniii, CgH^NOo, 
 
 Brieger, 
 
 Tainted meat, 
 
 Tetanizing poison. 
 
 
 f Xencki, 
 
 I CE.de Coninck 
 
 Pancreatic 
 
 a a 
 
 Collidin, C 8 H„X, 
 
 digestion, 
 
 
 
 
 Putrid pulp, 
 
 it it 
 
 Hydroeollidin, C 8 Hi 3 N, 
 
 Gautier and 
 
 Decayed fish, 
 
 Trembling, convulsions, 
 
 
 Etard, 
 
 
 arrest of heart in dias- 
 tole. 
 
 Parvolin, C 9 H 13 X, 
 
 Ibid. 
 f Guareschi 
 
 Ibid. 
 
 Very toxic. 
 
 
 and Mosso, 
 
 Putrid fibrin, 
 
 it a 
 
 Coridin, C 10 H 15 N, 
 
 CE. de Con- 
 
 
 
 
 { inck 
 
 Putrid pulp, 
 
 " " 
 
 Hydrolutidin, C 7 H n N, 
 
 j Gautier and 
 I Mourgues 
 
 Cod-liver oil, 
 
 Trembling paralysis. 
 
 Scombrin, C 17 H 3S X 4 , 
 
 (Gautier and 
 l Etard, 
 f Gautier and 
 I Mourgues 
 
 Decayed fish, 
 
 Trembling paralysis. 
 
 Morrhuin, C ]9 H 27 N 3 , 
 
 Cod-liver oil, 
 
 Diuretic. 
 
 Asellin, C 26 H 32 X 4 , 
 
 Ibid. 
 
 Ibid. 
 
 Convulsions; death. 
 
 Morrhuie acid, C 9 H 13 X0 3 , 
 
 Ibid. 
 
 Ibid. 
 
 Convulsions; death. 
 
 " C 7 H 18 N0 2 6 , 
 
 Pouchet, 
 
 Putrid meat, 
 
 Convulsions; death. 
 
 " C 5 H 12 X 2 4 , 
 
 Ibid. 
 
 Ibid. 
 
 Convulsions; death. 
 
 " CmHjoNjOo 
 
 Guareschi 
 
 Ibid. 
 
 Xon-toxic. 
 
 " C 5 H u N0 2) 
 
 Salkowski, 
 
 Ibid. 
 
 Ibid. 
 
 Mydalein, C 5 H n X0 2l 
 
 Brieger, 
 
 Human cad- 
 
 Fever; glandular hyper- 
 
 
 
 avers, 
 
 secretions. 
 
 Ptomatropin, C 5 H' n X0 2 , 
 
 Aurep, 
 
 Fish and meat 
 
 Action analogous to that. 
 
 
 
 poisons, 
 
 of atropin. 
 
 Ptomatocurarin, C 5 H n X0 2 , 
 
 Harkawy, 
 
 Putrid yeast, 
 
 Like curare. 
 
 Ptomatoconicln, C 6 H n X02, 
 
 Otto, 
 
 Cadavers, 
 
 Like conicin. 
 
 Ptomatoveratrin, CsH^NC^, 
 
 f Brouardel and Ibid. 
 1 Boutmy, 
 
 Like veratrin. 
 
 Tyrotoxin, C 6 H n X0 2 , 
 
 Vaughan, 
 
 Spoiled milk 
 and cheese, 
 
 it a 
 
 Gastrointestinal Putrefactions. The foregoing study of putrid 
 poisons and the facts concerning their production outside the organ- 
 ism find numerous applications in the history of gastrointestinal 
 putrefactions. 
 
 The microbes of the alimentary canal, having entered with bev- 
 erages and aliments, must evidently be the same as those which are 
 encountered in putrefactions in the free air. Although it is compara- 
 tively easy to determine the changes alimentary substances undergo 
 outside of the organism through the agency of bacteria, the problem 
 is far more delicate when the study of such phenomena occurring in 
 the intestine is undertaken. Here substances rapidly disappear by 
 absorption, and, on the other hand, it is difficult to decide which 
 changes are clue to digestive juices secreted by the organism and 
 which alterations are dependent upon bacterial action. Peptones, 
 
PATHOGENESIS OF INFECTIONS. I I :, 
 
 which are abundantly produced id both cases, may be mentioned ••>- 
 anexample. Ii may, therefore, be erroneout to con ider all microbic 
 products harmful. Certain micro-organisms are possibly useful and 
 must be considered as collaborators of the individual whom they 
 
 inhabit. Dr. Due.Ios asks whether microbee do qo1 accomplish a 
 complementary digestion nearly as important as digestion properly 
 so called. Iii fact, it is certain that several substance arenol tj 
 formed without the intervention of microbes. Such is uotably the 
 case with cellulose. It can be seen, therefore, how complex this 
 problem is and how interesting it would be to exactly determine the 
 role, importance, and signification of microbic fermentations in the 
 processes of digestion and nutrition. 1 
 
 We shall, therefore, endeavor to give a resume' of our knowli 
 of this subject. 
 
 As far as the carbohydrates are concerned, transformation by the 
 digestive juices consists in the production of dextrin and sugars 
 (glucose, levulose, maltose). The microbes form analogous substances 
 by saccharifying the starch or by interverting saccharose. Fermen- 
 tation may, however, go further and give rise to ethylic alcohol. 
 This fact is of great interest, since it perhaps accounts for the 
 presence of alcohol in the liver and brain of animals which have 
 never ingested this substance (J. Bechamp, Rajewski). 
 
 There is another series of bodies due to the action of figurate fer- 
 ments, namely: lactic, acetic, butyric acids, etc. These acids are 
 especially abundant in herbivora. 
 
 Microbes are able to break up neutral fats, but they act more 
 particularly upon albuminoids. Along with peptones, attributed to 
 the action of the pancreatic juice, there are amidate acids, leucin, 
 tyrosin, hypoxanthin, aspartic acid, and cinnamic acid : bodies of the 
 aromatic series, indol, phenol, skatol, and, finally, various g: - 3, 
 carbonic acid, hydrogen, sulphuretted hydrogen, and ammonia. We 
 have already stated that all these bodies are likewise produced when 
 albuminoid substances undergo putrefaction. It is important to 
 determine what modifications are properly due to the pancreatic 
 juice. The question has been studied by Kiihne. By accomplish- 
 ing artificial digestion in a medium containing 2 per 1000 of salicylic 
 acid, he prevented the development of germs and observed the pro- 
 duction of peptones and amidate acids, but he found no aromatic 
 
 1 Roger. Art. Physiologie de l'mtestin. Diet, encyclop. des se. medicale?. Paris, 
 1889, 4 sorie, t. xvi. 
 
116 INFECTIOUS DISEASES. 
 
 substances or gases. Other experimenters have obtained the same 
 results. It may, therefore, be stated that the intestinal gases and 
 aromatic substances depend upon the life of the microbes. This 
 fact explains the absence of these substances in the intestine of the 
 fetus and the newborn. 
 
 Toxicity of Fecal Matters. Prof. Bouchard was the first to 
 show, in 1882, that fecal matters contained alkaloids, some of which 
 are soluble in chloroform and others in ether. Fecal matter, studied 
 without separation of soluble substances, is highly toxic. According 
 to Prof. Bouchard, the extract of seventeen grams is sufficient to 
 kill a rabbit of one kilogram with diarrhea and convulsions. The 
 poisons are evidently manifold. A great part of the noxious effect 
 is due to potassium salts and ammonia. In fact, if these salts are 
 eliminated, the extract of 298 grams of feces is required to kill the 
 animal. It is certain that these figures have no absolute value and 
 that the toxicity of the matters is not constantly the same. 
 
 From a toxicological standpoint it may be stated that alcoholic 
 extracts are generally less active than aqueous. As to the toxicity 
 of diarrheal feces, those obtained during the stationary period are 
 the most noxious. The feces of a patient already convalescent have 
 been found less toxic than normal fecal matters. 
 
 Variations of Gastrointestinal Putrefactions. The in- 
 tensity of gastrointestinal putrefaction varies considerably with the 
 diet. Veal, particularly that of very young calves, forms in the in- 
 testine a sort of jelly which is difficult of absorption and offers a 
 favorable pabulum for microbes. On the other hand, milk diet 
 checks putrefaction (Biernachi) by reducing the number of bacteria 
 (Gilbert and Dominici). Even outside the organism this fact has 
 been observed. If milk is added to a mixture of muscles and pan- 
 creas, at the end of four days neither indol, skatol, leucin, nor tyrosin 
 is found (Winternitz). 
 
 Among the disturbances arising from autointoxications of intes- 
 tinal origin the most serious are those following ingestion of putrefied 
 meat, often characterized by grave and at times fatal symptoms. 
 The best known type of these disturbances is botulism or allantiasis. 
 It has been well studied in Germany where alimentary intoxications 
 are frequent from the use of imperfectly cooked sausage, which not 
 infrequently contains a great amount of ptomains and microbes. 1 
 
 1 For the study of alimentary intoxications, consult : Netter, Des poisons chimiques 
 qui apparaissent dans les matieres organiques en decomposition, et des maladies qu'ils 
 
PATHOGENESIS OF INFECTIONS. 117 
 
 Alimentary poisoning does not, however, always assume thegp 
 appearance observed id typical cases of botulism. Simple gastro 
 intestinal disturbances often follow the ingestion of slightly altered 
 meat or other tainted food. There is vomiting, though not in every 
 case, and especially diarrhea, which is profuse and extremely fetid. 
 In these instances the process is one of intoxication, the elements 
 of which originate in the intestine under the influence of microbes 
 contained in the loud. 
 
 Dr. Cassedebat 1 found in preserves aumerous toxic alkaloids, sev- 
 eral of which resisted boiling. Under the influence of alkaline bicar- 
 bonates, some of them produced a penetrnlm<r and persistent odor 
 which is also found in the air exhaled by animals which have ingested 
 these toxic bases. 
 
 Tainted fish and preserved fish represent another source of danger. 
 Brieger, Gautier, and others have discovered numerous ptomaine 
 engendered in putrefied fish. Disturbances are frequent as a result 
 of the ingestion of sardines, salmon, and particularly codfish. The 
 process is the same as in the case of meat. We must take into 
 account both the microbes and the ptomains which are secreted by 
 them, as was demonstrated by Duvillier. 
 
 Crustaceans and mollusks decompose more easily than fish. The 
 disturbances produced by tainted prawn and crabs have long been 
 described. One of the most remarkable observations is that reported 
 by Dr. Rapin (of Lausanne) in 1877. Crabs were consumed one day 
 without inconvenience; the following day nine persons ate some. 
 After a period of incubation of sixteen to fifty-five hours, those 
 who had eaten began to vomit, had sanguinolent diarrhea, and 
 presented a scarlatinoid eruption. One of the victims died on the 
 twenty-third day with typhoid-like symptoms. A clog which in- 
 gested some of the crabs manifested no disturbance. 
 
 Such accidents are most often due to preserved lobster, which, 
 while always unhealthful, is particularly dangerous when the con- 
 tainer has been open for a day or two. 
 
 A ptomain, tyrotoxin, as already stated, is found in tainted milk. 
 The same is encountered also in spoiled cheese, ice-cream, ices, and 
 
 peuvent provoquer. Arch. g£n. de medecine. 1SS4: Roger. Fermentations et putrefac- 
 tions intestinales. Gaz. des hdpitaux. March 31. 1SSS. Polin et Labit. Etude sur les 
 empoisonnements alimentaires. Paris, 1S90. (This is a very complete and highly 
 interesting monograph.) 
 
 1 Cassedebat. Bacteries et ptomaines des viandes de conserves. Revue d 'hygiene, 
 1S90, p. 659. 
 
J 1 8 IXFECTIO US DISEASES. 
 
 certain cakes. Altered milk causes disturbances, especially in chil- 
 dren, and at times even infantile cholera. 
 
 Condensed milk quite often becomes altered and liberates gases 
 which force, off the cover of the can. Dr. Cassedebat, who has made 
 a study of preserved milks, discovered no microbes in them, but only 
 aspergillus and a few mucedinea. Although harmless, the prepara- 
 tion is not then fit for consumption. 
 
 Autointoxications of Gastrointestinal Origin. No matter 
 how produced, a diarrhea is attended by intense intestinal putre- 
 faction, as we have already reported. Are the poisons thus formed 
 absorbed? Stich believed they were not. At the present day, how- 
 ever, there can be no doubt that they are. The terrible offensiveness 
 of the breath suffices to demonstrate this. In such cases Prof. 
 Bouchard was able to discover considerable quantities of ptomains 
 in the feces and urine. He found as much as 15 milligrams per 
 1000 grams of fecal matters, while the urine contained fifty times 
 more than under normal conditions. In more serious instances of 
 diarrhea, fermentation at times produces ammonia which may give 
 rise to capillary thrombosis (fermentative thrombosis of Hlava), and, 
 secondarily, to pseudomembranous enterites, with superficial necrosis 
 of the mucous membrane. 
 
 While putrefaction is increased in cases of diarrhea, in cases of 
 constipation, on the other hand, stagnation of the fecal matters 
 becomes a cause of intoxication by the absorption which it favors. 
 Therefore, a certain number of symptoms which are of the same 
 nature, though not as intense as those of diarrhea, are caused by 
 constipation. In fact, in both instances there is cephalalgia, fatigue, 
 nervous disturbances, and tumefaction of the liver. It is to be 
 noted, however, that in constipation the matters accumulated in the 
 intestine, being excessively hard, do not readily allow the transuda- 
 tion of the toxins they contain. 
 
 Constipation exerts curious effects upon the constitution of the 
 blood. By causing coprostasis in animals, Vanni 1 noticed that the 
 red corpuscles diminished in number and became less resistant to 
 destructive agents. 
 
 Although constipation is generally well borne by healthy individ- 
 uals, this is not the case in those who have received some trauma- 
 tism, in confined women, and in persons upon whom laparotomy has 
 
 1 Vanni. Sull' origin intestinale della chlorosi. II Morgagni, 1893, p. 533. 
 
PATHOGENESIS OF INFECTIONS. |]!i 
 
 been performed. In more than one such <■•■> <■ febrile pan 
 appeared which might well be suspected a i symptom* of epticemia, 
 I > 1 1 1 which have vanished with evacuation of the bowels imp! 
 the adminisl ration of an enema. 1 
 
 The old surgeons were not, therefore, wrong in preparing their 
 patients, and intestinal antisepsis practised for ;i few dayt before 
 abdominal operations renders real service. 
 
 Intestinal obstruction under all its forms internal strangulation, 
 invagination— presents the most striking picture of digestive auto- 
 intoxication. The theory of reflex action cannol accounl for the 
 clinical manifestations, and if has yielded to the toxic theory. In 
 fact, Senator has shown that, by lavage of the stomach, it. is possible 
 to cause the momentary disappearance of the symptoms of obstruc- 
 tion and that, by repeating this procedure, a cure may be effected. 
 This successful result has since been observed by several physicians, 
 notably by Drs. Bouchard and Chantemesse. 
 
 Prof. Bouchard has emphasized the importance of gastric intoxi- 
 cations by the study of dilatation of the stomach. Without intoxi- 
 cation it was impossible to explain the various manifestations ob- 
 served, especially the nervous symptoms which, in their mildest 
 forms, are characterized by prostration and a feeling of exhaustion at 
 the moment of wakening, and, in their graver expression, terminating 
 in aphasia, vertigo, tetany, and coma. Fetid sweat, cutaneous erup- 
 tions, congestion of the liver, albuminuria, peptonuria, trophic dis- 
 turbances, notably the nodes of the second phalanges, are likewise 
 referable to the formation of poisons. A few authorities go further 
 and believe the same process is responsible for the deeper alterations 
 of the osseous system, osteomalacia in adults, and, according to 
 Dr. Comby, rachitis in children. 
 
 Poorly digested substances are easily attacked by microbes in the 
 stomach and intestine. When, however, digestive disturbance is 
 attended by hyperchlorhydria, extremely toxic substances are pro- 
 duced in the stomach which are responsible for dyspeptic tetany and 
 coma. The question has been very carefully studied by Kulneff, 
 Bouveret, and Devic, but it is still unknown what part is to be attrib- 
 uted to microbes in the genesis of these poisons and of ethyldiacetic 
 acid. This acid has been credited with an important role in the 
 pathogenesis of comatose phenomena, analogous to those produced 
 
 1 Kustner. Zur Kritik der Beziehungen zwischeu Faecalstase und Fieber. Zeitschr. 
 fur klin. Med.. 1882, Bd. v. 
 
120 INFECTIOUS DISEASES. 
 
 by diabetes, which are observed in dyspepsias, dilatation, ulcer, or 
 cancer of the stomach, and after the ingestion of tainted meat. 
 
 The experiments of Dr. Boix 1 demonstrate that butyric acid is 
 capable of inducing atrophic cirrhosis; lactic and valeric acids exert 
 a similar, though less intense, action ; acetic acid is the most harmful, 
 for it is sclerogenous and, at the same time, produces cellular degen- 
 erations. 
 
 Here is a series of facts which conclusively establish that secretory 
 disturbances and putrefactions of the alimentary canal give rise to 
 a great number of noxious products which are capable of causing 
 immediate accidents or, in the long run, induce visceral lesions. 
 
 Finally, it is well to remark that in cases of nephritis, hepatic 
 affections, cardiopathies, morphinomania, tuberculosis, and evidently 
 also in typhoid fever and cholera, there are profound alterations in 
 the stomach and intestine, and, consequently, putrid fermentations 
 are produced, the effects of which are added to those of the primary 
 disease. 
 
 The Toxins of the Pathogenic Microbes. 
 
 Multiplicity of Microbic Toxins. The idea of attributing the 
 development of infectious diseases to intoxication is very old. In 
 the presence of bacteriology it seemed for a moment to have lost 
 ground. Soon, however, the first experimenters themselves began 
 to suspect that microbes are not everything, and that toxins secreted 
 by them played a role of prime importance. Diligent and methodic 
 researches were undertaken on every hand and a great number of 
 toxic bases of microbic origin were described. 
 
 Most of these bases do not contain oxygen, and, like the analogous 
 alkaloids found in highly organized plants, they are not crystallizable. 
 They are oily, colorless substances, with a cadaveric odor, seldom 
 with an agreeable one. They are soluble in alcohol, ether, and all 
 the usual solvents of alkaloids, and, like them, form salts which 
 crystallize. Other less numerous bases are oxygenated and conse- 
 quently crystallizable. 
 
 These results seemed to demonstrate the analogy between bacterial 
 and vegetable alkaloids. Soon, however, objections were raised. It 
 was pointed out that the ptomains extracted from cultures were far 
 from possessing the same toxic potency as the total culture, and did 
 
 1 Boix. Le foie des dyspeptiques. These de Paris, 1894. 
 
PATHOGENESIS OF INFECTIONS. 12 1 
 
 not produce the same phenomena. It wa recognized that, at in the 
 case of piii rid poisons, i In- substances soluble in alcohol are not the 
 most active, hut, on the contrary, tho.se precipitated by this liquid. 
 
 It seems certain that the bacterial poi on are very complex and, 
 consequently, very unstable. They are, therefore, easily decom- 
 posed in the course of chemical manipulations, and whal i- obtained 
 at the end of the researches is not the primary poison, bul one 
 derived therefrom. The toxalbumins, for instance, probably contain 
 an alkaloidal nucleus which is separated from them on the slightesl 
 occasion. Therefore, one can never be sine of having obtained the 
 primary body. Although methods of investigation have been mul- 
 tiplied, no absolutely reliable method has been found. 
 
 In view of the uncertainty of methods, it is well to precisely deter- 
 mine the initial toxicity of the sterilized culture. The active sub- 
 stances are subsequently separated without overlooking the fact that 
 all reagents, including alcohol, which is so frequently employed, may 
 decompose the toxic molecule. By combining the methods the 
 conviction is reached that the majority of microbic poisons are pre- 
 cipitated by alcohol and adhere to the precipitates which form the 
 various mineral salts in the culture fluid. This is, for instance, what 
 occurs with aluminum hydrate and calcium phosphate. In view of 
 these chemical results and of the fact that minute amounts produce 
 violent results, toxins have been considered as ferments. Recently, 
 however, under the influence of the researches of Brieger and Fraen- 
 kel, they have been designated by the vague term toxalbumins, and 
 at times they are classed with nucleo-albumins. It is to be remem- 
 bered that certain microbic poisons possess characters comparable 
 to those of albumoses and peptones. Hence, the names toxal- 
 bumoses and toxopeptones applied to them. 
 
 In spite of the divergencies of detail, a fact is manifest, viz., that 
 the toxins are complex molecules possessing certain characters of 
 a ferment. Like the latter body, they are very unstable, adhere to 
 various precipitates, and are altered and decomposed by heat and 
 light. Like ferments and albumins, they are precipitated by alcohol, 
 and are only slightly or slowly dializable. They may. therefore, be 
 considered as proteid substances. "They are.'" says Prof. Gautier, 
 " complicated ptomains." 
 
 It has been asked whether the question was rendered any clearer 
 by comparing toxins to ferments — i. e.. to substances the nature of 
 which is unknown and which reveal themselves bv their functions 
 
1 22 INFECTIO US DISEASES. 
 
 .alone. A ferment is a complex substance which has received from 
 living substance a certain degree of vital activity. It is, as Buchner 
 states, "a semiliving matter." At all events, it is the highest 
 expression of lifeless matter. Under these conditions the action of 
 toxins is no more mysterious than that of ordinary ferments. The 
 objection which consists in excluding toxins from this group because 
 they do not hydrate albumin and do not act upon sugar is of little 
 value. This is like asserting that pepsin is not a ferment because 
 it does not convert starch into sugar. The microbic cell, like the 
 animal cell, possesses different ferments; in other words, it is apt 
 to transmit different forms of energy to different molecules. 
 
 In brief, bacterial poisons are complex and recognize several 
 origins. The protoplasm of parasites contains proteins which have 
 been well studied by Buchner. The culture fluid contains poisons 
 which are formed by secretion or by synthesis and belong to the group 
 of albuminoids. Besides those already referred to, there is one more 
 toxin to be mentioned, namely, mucin, which is encountered in the 
 cultures of various microbes, notably that of the tubercle bacillus 
 (Weyl). 
 
 Action of Toxins upon the Organism. The effects produced 
 by microbic toxins vary evidently according to the pathogenic agent 
 under consideration. However, the symptoms observed may be 
 divided into three groups. Some are produced at the point of intro- 
 duction of the active substance and constitute the local lesions. 
 Others express the impregnation of the entire economy, and are 
 general manifestations. Lastly, there are symptoms indicating a 
 selective action of the toxin upon some organ, apparatus, or tissue. 
 
 The local lesions are not constant. When any exist they vary, 
 even for the same toxin, according to the activity of the latter, the 
 point of introduction, and the amount of substance employed. The 
 researches which I have pursued with the diphtheria toxin resulted 
 as follows: When injected beneath the skin it produces, as is known, 
 a very marked edema. When spread upon a mucous membrane 
 exposed to the air, it gives rise to the formation of false membranes. 
 If, however, it is very active or the animal is highly sensitive to its 
 action, no local lesion is produced, but there occurs a general intoxi- 
 cation which rapidly ends in death. 
 
 Toxins also give rise to general disturbances. These are the only 
 symptoms observed when the poison is introduced directly into the 
 veins. No matter what the mode of introduction may be, or what 
 
PATHOGENESIS OF INFECTIONS. 123 
 
 amount is introduced, the symptoms are never manifested instan- 
 taneously. Contrary to what occurs immediately after an alkaloid 
 is injected, in most microbic intoxications there is a period of lat< 
 which lasts from :i few hours toadayortwo. The mosl impor- 
 tant genera] manifestation is fever, which ie accompanied by other 
 phenomena: urinary disorders, secretory modifications, exchanges 
 
 of gases, etc. 
 
 When the toxin is absorbed or when it is injected directly into the 
 blood it may produce in the viscera a series of accidente varying 
 with the poisonand the animal. They consist in functional disturb- 
 ances or in lesions, notably cellular degenerations. It is conceivable 
 therefore, that if immediate death is avoided the intoxicated animal 
 may later succumb to a progressive cachexia which is sufficiently 
 accounted for by the numerous visceral alterations discovered al the 
 necropsy. In other instances, an organ having been more particu- 
 larly affected, some organic affection— chronic nephritis, myocardi- 
 tis, cirrhosis, or myelitis— is developed, which pursues its own inde- 
 pendent course. 
 
 Description of Principal Toxins. Among infectious dise 
 there is a group the pathological physiology of which is incompre- 
 hensible if the action of a toxin is not admitted. I refer to those 
 maladies the pathogenic agent of which remains localized at the point 
 of introduction, viz., diphtheria, tetanus, cholera, gaseous gangrene, 
 and symptomatic anthrax. 
 
 The diphtheria toxin, discovered by Roux and Yersen, may be very 
 active, its energy not being necessarily related to the pathogenic 
 power of the culture. A very virulent bacillus is not necessarily 
 very toxinogenous. An active toxin is that which kills a guinea- 
 pig of an average weight in a close of 0.1 c.cm. With the bouillon of 
 Martin, 0.002 c.cm. suffices to kill a guinea-pig weighing 500 grams. 
 If we remember that one cubic centimetre of the fluid gives one cen- 
 tigram of dry residue, say 0.0004 of organic matter, and that the 
 toxin represents only one part of this organic matter, we can conceive 
 the prodigious activity of the diphtheritic poison. An ordinary diph- 
 theria, toxin is sufficient to poison a weight of living being 20,000,000 
 times greater than its own. 
 
 Among the chemical substances which diminish the energy of this 
 toxin are lactic, acetic, and tartaric acids. However, by again neu- 
 tralizing the medium, we may in great part at least renew the 
 toxicity. Oxidizing bodies, such as potassium permanganate, neu- 
 
1 24 IXFECTIO US DISEASES. 
 
 tralize its effects. The reducing substances, such as sulphuretted 
 hydrogen, are indifferent. Iodine trichloride and iodin-water 
 weaken the action of the toxin and permit its employment as a 
 vaccine. 
 
 All animals are not equally sensitive to the diphtheritic poison, and 
 those which are refractory to the living bacillus are so to the toxin. 
 The guinea-pig is readily poisoned by it ; the rabbit is less susceptible, 
 and the dog still less. The mouse and the rat endure high doses. 
 
 Subcutaneous injection produces a local edema, which is often 
 very marked, and congestion of the corresponding ganglia. In the 
 rabbit it is followed by the formation of pseudomembranes, often 
 very extensive and thick, occupying the larynx, trachea, and at 
 times the intrapulmonary bronchial tubes. Upon the exposed mu- 
 cous membranes the lesion remains local. When introduced into the 
 alimentary canal, this toxin produces no effects. 
 
 Subcutaneous or intravenous injection of the toxin is not followed 
 by any immediate symptoms. At the end of a period which varies 
 with the activity of the poison and the quantity introduced, the 
 guinea-pigs become cold and are seen to stay in a corner of their 
 cage ; they subsequently fall into a somnolent state and die in hypo- 
 thermia. Rabbits frequently suffer from diarrhea. At the necropsy 
 pulmonary congestion and edema, pleural effusion, congestion, and 
 at times hemorrhages into the suprarenal capsules are found in the 
 guinea-pig. In the rabbit the dominant changes are intense conges- 
 tion of the liver and kidneys, with fatty degeneration of the cells r 
 while the suprarenal capsules are generally intact. 
 
 When very small doses are injected, paralytic phenomena, espe- 
 cially in the rabbit, may be observed during life. At the necropsy 
 alterations of the nervous system are frequently discovered. It is also 
 in such cases that myocarditis is found, which has been well studied 
 by Mollard, Regaud, and others. 
 
 The Tetanic Toxin. In the early studies of tetanus experimenters 
 resorted, as is commonly the case, to complex methods, which subse- 
 quently were replaced by simpler procedures. Brieger, who was the 
 first to investigate the poison of tetanus, endeavored to obtain chemi- 
 cally defined bodies. By experimenting upon the arm of a man 
 suffering from tetanus, and upon impure cultures, he obtained, apart 
 from the putrefactive bases already known, four new bases : tetanin r 
 whose chemical composition is established by him to be C 13 H 30 N 2 O 4r 
 and causes trismus and then generalized tetanus in the mouse; 
 
PATHOGENESIS OF INFECTIONS. 126 
 
 tefanofoxin, which produces convulsions or paral} es; pa mot< 
 which gives rise to clonic and ionic spasm ; lastly, a base which 
 stimulates the salivary and lacrymal secretion . 
 
 Kitasato and Weyl, experimenting with pure cultures, detected 
 
 tetanin and traces of totanotoxin, hut these bases aci only in enor 
 mous doses. As a matter of fact, the true poison is of a different 
 nature, as has been demonstrated perfectly by Kund Faber. Thifi 
 author simply filters the culture fluid through porcelain and obtains 
 
 a toxin resembling diastases, which is destroyed by :ileohol or a tem- 
 perature of 149° F. (65° C). Injected into animals, it produces 
 
 tetanus after a period of incubation. It behaves, therefore, like 
 the diphtheritic toxin. 
 
 At present it is known that the tetanic poison is more of an albu- 
 minoid nature than a ptomain. Obtained by filtration of cultures, 
 the poison is of such strength that yiruinro c - cm - suffices to kill a 
 mouse. Dr. Nicolas, having accidentally pricked his own skin 
 with the point of a needle charged with the toxin, was taken sick, 
 after four days, with tetanus which proved to be of a benign char- 
 acter. 
 
 Two theories have been advanced with regard to the pathological 
 physiology of tetanus: one, originated by Autokeatow and developed 
 by Courmont and Doyon, admits an action of the poison upon the 
 sensory nerves; the other, defended by Bruner, assumes increased 
 excitability of the nerve centres — i. e., a modification analogous to 
 that produced by strychnine. 
 
 The Cholera Toxin. The choleraic poison was first studied by Petri, 
 who considered it as a toxopeptone, and by Hueppe and Scholl, who 
 cultivated the vibrio in egg albumin without being able to completely 
 remove from their preparations of toxin sulphuretted hydrogen and 
 alcohol (Gruber and Wiener). 
 
 The question has further been studied by "Westbroock, who ob- 
 tained a hypothermizing poison: by Sanarelli, who isolated a toxin 
 acting through the alimentary canal: by Brieger and Fraenkel. who 
 prepared an unstable protein. The most important contributions 
 have come from Pfeiffer and Ransom. The results are, however, 
 contradictory. Pfeiffer asserts that the poison resides in the body 
 of the microbe, while Ransom contends that the toxin is a soluble 
 substance which resists a temperature of 212° F. (100° C.) and. in 
 small doses, causes death in collapse: in high doses, its action is 
 instantaneous. 
 
1 26 ISFECTIO US DISEASES. 
 
 The question was taken up and completely studied by Drs. Metch- 
 nikoff, Roux, and Taurelli-Salimbeni. These authorities began by 
 exalting the vibrio by means of a very ingenious procedure, which 
 consists in cultivating it in small capsules of collodion introduced 
 into the peritoneum of guinea-pigs. When the microbe has become 
 quite energetic, it is transferred to a fluid containing 2 per cent, of 
 gelatin, 2 per cent, of peptone, and 1 per cent, of sea salt. The most 
 active poison is obtained on the third or fourth day. A dose of 
 0.3 c.cm. per 100 grams kills a guinea-pig in sixteen to twenty-four 
 hours. This poison differs from the cholera and diphtheria toxins 
 in that it resists boiling. It is destroyed by sunlight, precipitates 
 ammonium sulphate and strong alcohol. Injected into guinea-pigs, 
 it produces prostration, meteorism, and diarrhea. The animals 
 succumb in hypothermia. 
 
 Toxins of Gaseous Gangrene and Symptomatic Anthrax. The bacilli 
 of gaseous gangrene and of symptomatic anthrax are two very closely 
 related anaerobics. They resemble the preceding microbes in their 
 tendency to remain localized, although they invade the organism 
 more easily, at least when the question is one of small laboratory 
 animals. 
 
 The poison of gaseous gangrene, studied by Roux and Chamber- 
 land, and more completely by Besson, when injected in a dose of 
 3 c.cm. to 5 c.cm. into the peritoneal cavity of guinea-pigs weighing 
 from 450 to 600 grains produces grave symptoms with hypothermia. 
 The animals recover, however. Introduced subcutaneously, the 
 poison gives rise to considerable edema and at times to an eschar. 
 The latter result is of great interest, since it elucidates the mechan- 
 ism of gangrenous lesions. To kill a guinea-pig of 300 to 400 
 grams, the injection of 5 c.cm. to 10 c.cm. is required. 
 
 It is not easy to state whether the poison of gaseous gangrene is 
 identical with or analogous to that of symptomatic anthrax, since 
 researches have not been pursued under altogether similar condi- 
 tions. 
 
 The Toxin of Anthrax. We now come to that group of microbes 
 which manifest a tendency to invade the entire organism. The list 
 may properly be headed by the bacillus anlhracis and the microbe 
 of chicken cholera. 
 
 The preparation of the anthrax toxin seems to be quite difficult, 
 and its study has been the subject of numerous contradictory re- 
 searches. The poison seems to remain long enclosed in the bacterial 
 
PATHOGENESIS OF INFECTIONS. \2l 
 
 cellule. It diffuses tardily and only in media prepared in a pedal 
 manner. 
 
 The best work on this subject is due to Marmier. This author 
 cultivated the bacillus in a medium containing 40 per cent, of peptone 
 and 4 per cent, of glycerin. The active substance i extracted by 
 means of ammonium sulphate and alcohol, [f the culture has been 
 kept at 96.8° F. (36° C), the toxin is Blight in amounl ; it i- abundant 
 if the medium has been kept at 68° F. (20° C.) for a fortnight. This 
 toxin, injected into animals, causes a U'vcv which is ushered in toward 
 the fourth hour, and reaches its maximum the following day. Diar- 
 rhea makes its appearance, the animals become thin, cachectic, and, 
 after convulsions, succumb in hypothermia. 
 
 Toxins of the Bacilli of Hemorrhagic Septicemias. Some researches 
 have been made on various agents of hemorrhagic septicemia-, not- 
 ably those of hog cholera. DeSchweinitz found albuminoids (suchole- 
 albumins) and a ptomain (sucholetoxin) toxic for the guinea-pig. 
 Novy isolated a toxalbumin and a protein. Voges 1 has also done 
 important work bearing on this subject. His conclusion is, with 
 regard to the toxins, that the poison is contained in the microbic 
 cells. This is proved by treating the cultures with chloroform, car- 
 bolic acid, or tricresol. Subjection to a temperature of 122° F. 
 (50° C.) or 140° F. (60° C.) or to ebullition for ten minutes likewise 
 yields good results. Absolute alcohol exerts a very marked destruc- 
 tive action upon the toxin. 
 
 Among the septicemic agents observed in man, proton* vulgaris 
 may be mentioned. Its sterilized cultures are almost as active as 
 the living cultures and produce about the same general as well as 
 local effects. According to Foa and Bonome, the chief toxin is nervin . 
 which is abundantly present in the cultures. 
 
 Toxins of the Bacillus Septicus Putidus. The soluble products of the 
 B. septicus putidus are very active. Half a cubic centimetre is suffi- 
 cient to kill one kilogram of rabbit within five to fourteen days. A 
 dose of 20 c.cm. to 30 c.cm. kills in a few hours, and 45 c.cm. proves 
 fatal in a few minutes. In such acute cases there is paresis and 
 convulsions, death supervening by arrest of respiration. 
 
 The Pyocyaneus Toxin. Like the preceding, this bacillus may be 
 observed in man, but its chief interest is due to the experimental 
 
 1 O. Voges. Kritisehe Studium und exp. Untersuchungen iiber die Bakterien der 
 h:\moiTkagiscken Septikamie und die durch sie bewirkter Krankkeitsformen. Zeitsekr. 
 fur Hygiene und Infektionsfrrankheiten, 1S96, Bd. xxiii. 
 
128 IXFECTIOUS DISEASES. 
 
 researches to which it has been subjected. Everyone is aware of 
 the interesting work of Charrin, who was able, with sterilized cultures, 
 to produce in animals symptoms identical to those caused by the 
 microbe itself. 
 
 The Toxins of Colon Bacillus. On account of the important role 
 which the colon bacillus plays in the organism, even under normal 
 conditions, it is proper to give it special attention in this cursory 
 review. 
 
 The soluble products secreted by this microbe, or rather by the 
 various bacteria constituting the group of colon bacilli, have been 
 well studied by Denys and Brion, and particularly by Gilbert. 1 From 
 these researches it is shown that the toxins of the colon bacillus are 
 of varying potency according to the virulence of the germ; moreover, 
 they are the more powerful the older the culture. Nevertheless, to 
 cause death, Gilbert had to inject very large doses, varying from 
 37 c.cm. to 74 c.cm. per kilogram of animal. 
 
 Rabbits which receive the sterilized culture become weak and the 
 muscles manifest fibrillary trembling. Convulsions and nystagmus 
 then supervene. The third stage is characterized by a violent 
 tetanus, to which the animal succumbs. The nervous phenomena 
 depend upon spinal changes easily discoverable in frogs. 2 The intoxi- 
 cation in this animal is comprised in three stages: a stage of initial 
 paresis, a stage of muscular hyperexcitability, and a stage of par- 
 alysis. The tracings which I have obtained clearly show that the 
 poison acts upon the spinal cord and, secondarily, upon the muscles. 
 
 The poison of the colon bacillus, the effects of which have just been 
 referred to, is constantly produced in the intestine. A part of it is 
 arrested and transformed by the intestinal epithelium, as was demon- 
 strated by Denj^s; another part penetrates the organism. However, 
 since absorption is effected by the portal vein, the liver may exercise 
 a protective role, and, as a matter of fact, we have established that 
 this gland is capable of arresting and transforming the intestinal 
 poisons. That portion escaping the action of the liver is eliminated 
 by the urine and contributes to the toxicity which this secretion 
 presents under normal conditions. Gilbert justly remarks that cer- 
 tain symptoms are common to intoxications produced either by the 
 
 1 Gilbert. Des poisons produits par le bacille intestinal d'Escherich. Soc. de biol- 
 ogie, February 25, 1893, p. 214. 
 
 2 Roger. Etude sur la toxicite des produits solubles du B. coli communis. Arch, 
 de physiol., July 1, 1893. 
 
PATHOGENESIS OF INFECTIONS. 129 
 
 urine or by the colon bacillus, and that, moreover, when putrefac- 
 tions of the intestine are checked by antiseptics, the toxicity of the 
 
 urine is at the same time reduced. 
 Under various pathological conditions the virulence of the colon 
 
 bacillus increases. In some instances, the microbe invades the organ- 
 ism and produces therein the soluble substances the effect* of which 
 have just been referred to. These effects are more pronounced w hen 
 the protective organs of the economy are more or less altered by 
 the disease. 
 
 The author made an experimental study of the toxin- produced 
 by a colon bacillus representing the cause of a variety of dysentery. 1 
 
 The cultures of this colon bacillus inoculated into rabbits proved 
 extremely virulent. A few drops injected into a vein caused death 
 in less than a day, at times in six hours. This microbe produced 
 very strong toxins in the culture media. When the culture medium 
 was composed of equal parts of bouillon and serum, instead of simple 
 bouillon, the results were more interesting. At the end of eight days 
 the culture was sterilized by means of chloroform, which was subse- 
 quently removed by decantation and evaporation. The fluid thus 
 prepared was so very toxic that ten drops injected into the veins of 
 a rabbit of 2 kilograms sufficed to produce fever, diarrhea, and, 
 finally, death in twenty-four or forty-eight hours. With a second 
 sample, furnished by a bacillus exalted by passages through animals, 
 18 c.cm to 20 c.cm. caused death within an hour or two. 
 
 One of the first symptoms produced by the toxin is diarrhea, 
 which is at times extremely profuse, amounting to a continuous 
 evacuation. Hence the rapid loss of weight suffered by the animals. 
 The toxin prepared with the exalted microbe exerted a far more 
 energetic action, but gave rise to very little, if any. diarrhea. It 
 may, therefore, be admitted that the intestinal flux eliminates not 
 only the poisons originated in the digestive canal, but also the noxious 
 substances which may have penetrated the economy. 
 
 The Toxins of the Pyogenic Microbes. The pus cocci constitute a 
 group, at the head of which we would place the staphylococcus. The 
 staphylococcic toxin is of considerable interest with reference to the 
 study of suppuration. It will be treated in the chapter devoted to 
 this question. The poison may likewise give rise to general mani- 
 
 1 Roger. Les toxines du colibacille de la dysenterie. Ann. de la soc. de med. de 
 Gand, 1900. p. 139. Le colibacille de la dysenterie. Presse med., July 4. 1900. 
 
 9 
 
130 INFECTIOUS DISEASES. 
 
 testations. In this respect, however, its history is not so important 
 as that of the streptococcus. 
 
 The study of the soluble products of the streptococcus was first 
 made by Manfredi and Traversa. In a highly remarkable memoire 
 these authors have shown that the cultures of this microbe, freed 
 from all figurate elements by means of porcelain filters, are toxic for 
 the frog, guinea-pig, and rabbit. In the last-named animal, thirty 
 to fifty minutes after subcutaneous injection of the filtered fluid, a 
 certain degree of somnolence is observed, then a slight paresis of the 
 extremities. In most cases the animal recovers in a few days. 
 
 To obtain the toxic substances, the author 1 cultivated the strep- 
 tococcus in thick bouillon protected from the air by a layer of oil. 
 The fluid was filtered at the end of fifteen clays and injected into the 
 veins of a certain number of rabbits. The fatal dose, which varied 
 somewhat from one culture to another, oscillated generally between 
 13 c.cm. and 20 c.cm. per kilogram. After the injection the animals 
 remained in a state of somnolence; the next day they presented a 
 very profuse diarrhea. Death supervened at the end of two or three 
 days. 
 
 To establish the nature of the toxin the filtered fluid was treated 
 with ten times its volume of absolute alcohol. The resulting abun- 
 dant precipitate was washed with alcohol and reclissolved in a 7 per 
 1000 salt solution. The alcoholic fluids were united and evaporated 
 at a low temperature. The residue was then treated with salt water. 
 Two extracts were thus obtained which were studied separately. 
 The alcoholic extract did not prove to be toxic. On the other hand, 
 the aqueous extract gave rise to the same disturbances as the total 
 culture, except that higher doses were required. 
 
 The toxin of the streptococcus when submitted to a temperature 
 of 219.2° F. (104° C.) is considerably weakened. This is true of the 
 total culture as well as of the aqueous extract. 
 
 The Toxin of the Pneumococcus. The toxin of the pneumococcus, 
 which has been prepared and well studied by Drs. Carnot and Four- 
 nier, is so active that a few drops of it injected into the lung produce 
 a focus of pneumonia characterized by flatness, crepitant rales, and 
 bronchial breathing. At the necropsy, fibrinous pneumonia, com- 
 parable to that observed in man, is discovered. By varying the 
 
 1 Roger. Action des produits solubles du streptocoque de PeYysipele. Soc. de 
 biologie, July 4, 1891. Contribution a P£tude experimentale du streptocoque de Pery- 
 sipele. Revue de m<§d., December, 1892. 
 
PA THOQ ENE8I8 OF XNFEi TIO N8. 1 :; ] 
 
 experimental conditions, oilier varieties of pulmonary lesii 
 
 he produced, sucli ns liemorrhagic pneumonia, gray hepatization, 
 
 and abscess of the Lung. 
 
 The Toxin of Typhoid Fever. The I yplioid lo.\in has been Studied 
 
 by Brieger and Fraenkel, who believed il bo bea toxalbumin, Sana- 
 relli experimented with extracts obtained by macerating the bacilli 
 for six months. The toxin thus prepared produces hypothermia, 
 
 abdominal meteorism, mucous and sanguinolentstools. Death occurs 
 in coma. 
 
 According to Chantemesse and Ramond, the toxin is rapidly 
 destroyed in the cultures by oxidation. These authors employ ae a 
 medium a bouillon prepared with spleen digested by fresh pepsin 
 derived from the stomach of a pig. The poison manifests the great- 
 est energy on the fifth or sixth day. It is very active for the guinea- 
 pig, rabbit, sheep, dog, and especially the horse. If the amount 
 injected into a rabbit is very small, hyperthermia is the result : if it 
 is large, then hypothermia occurs. At the same time diarrhea makes 
 its appearance, followed by respiratory and circulatory disturbances. 
 The necropsy reveals congestion of the intestine and abdominal 
 organs, liver, kidneys, and spleen. In his more recent researches, 
 Chantemesse made a very minute analysis of the action exerted by 
 this toxin upon the heart and nervous system. 
 
 Toxins of Glanders. We shall mention one more toxin, that of 
 glanders, which, according to Finger, produces rapid death, or, if the 
 dose is less strong, a progressive cachexia accompanied by paralytic 
 manifestations. Babes and Motoc isolated from the cultures a sub- 
 stance insoluble in alcohol and possessing a very marked thermogenic 
 action. Its injection produces spasms, and, if the injections are 
 repeated, nephritis results, and death supervenes in marasmus. 
 
 Poisons Found in Infected Organisms. Aside from the poisons 
 due to the microbe, the diseased organism itself elaborates some. 
 These may be divided into three groups: 
 
 1. Poisons produced b}^ the organism under the influence of patho- 
 genic microbes. This group includes poisons which cannot originate 
 in culture media, the microbes attacking the constituent elements of 
 the invaded organism directly or through the ferments which they 
 secrete. 
 
 2. Poisons derived from the alimentary canal in the course of 
 infections, in which putrefaction is always increased. 
 
 3. Poisons derived from disassimilation, which is increased and 
 
132 INFECTIOUS DISEASES. 
 
 perverted. To this cause are probably clue the profound modifica- 
 tions occurring in the chemical constitution of the organism in the 
 course of febrile maladies. The alkalinity of the blood is diminished : 
 instead of representing 4 to 5 grains (238 to 280 milligrams) of soda, 
 it corresponds to no more than about three-fourths of a grain (40 
 milligrams), the change being due to the increase of acids, notably 
 formic, acetic, diacetic, ^-oxybutyric, and lactic acids, and volatile 
 fatty acids. 
 
 The increased acidity results in increased elimination of ammonia. 
 The extractive material and amidate bodies increase at the same 
 time. The nutritive disturbances engendered by infections are also 
 expressed by other modifications in the excretion of nitrog- 
 enous bodies — i. e.,serinuria, globulinuria, albumosuria, and probably 
 acetonuria. To these should be added toxalbumins, which were 
 detected by Alt in the vomitus of choleraic patients, and by Brieger 
 and Wassermann in the urine of an erysipelatous subject. 
 
 Toxicity of the Blood and Urine in Some Infections. The 
 toxicity of the blood may be increased in very notable degree. Very 
 grave accidents and death are the results when 10 c.cm. to 15 c.cm. 
 of the serum of a rabbit suffering from anthrax is injected into a 
 healthy rabbit. Bose demonstrated that the serum of cholera- 
 stricken patients injected into rabbits, in the proportion of 3 c.cm. 
 to 5 c.cm. per kilogram, causes death within twelve to sixteen hours 
 with choleriform symptoms. 
 
 The toxic substances have most often been sought for in the urine. 
 Some have been content to study its total toxicity; others have 
 endeavored to isolate from the urine some definite substance ; in most 
 cases a ptomain. In 1882 Prof. Bouchard detected in the urine of 
 typhoid patients the presence of alkaloids, of which he obtained as 
 much as one milligram a day. Two years later Drs. Lepine and 
 Guerin made the same observation in cases of typhoid fever and of 
 pneumonia. Dr. Lepine further recognized, with Dr. Aubert, that 
 the toxic substances of organic nature are considerably increased in 
 febrile urine, while mineral poisons suffer no variation. 
 
 The second method consists in studying the toxicity of the urine 
 without reference to the nature of the poison to which it is due. 
 It is by this procedure that Prof. Bouchard revealed the special 
 properties possessed by the urine of cholera patients. It may be 
 stated, without exaggeration, that his work is the fundamental study 
 on this subject, and has been taken as a model for further researches. 
 
PATHOGENESIS OF INFECTIONS. 183 
 
 Dr. Lupine discovered a toxic alkaloid in the urine of pneumonia 
 patients. Tin- amount of the alkaloid increasei in proportion to the 
 intensity of the disease and possesses the power to arresl the heart 
 in diastole. The presence of alkaloids in the mine of pneumonia 
 cases has been confirmed by the researches of Griffiths and Albu. 
 
 Researches pursued with Dr. Gaume 1 showed us, contrary to all 
 expectation, that the toxicity of the urine diminishes as the di 
 progresses. At the end of the stationary stage the toxicity i- often 
 no more than half or one-third of the normal. Later, at the moment 
 of defervescence, a urotoxic crisis occurs, and the toxicity again 
 rises above the normal. In souk; instances it exceeds but slightly 
 the normal toxicity; in others it acquires a double, treble, or even 
 quadruple value. This excessive toxicity lasts twenty-four to forty- 
 eight hours. During convalescence the urine presents a variable 
 toxicity, which may be equal to, below, or above the normal. 
 
 Similar researches have been made by various experimenters upon 
 the toxicity of the urine in erysipelas, variola, scarlatina, typhoid 
 fever, tetanus, malaria, influenza, tuberculosis, and leprosy. It is 
 curious to note that, in most cases, the poison detected in patients 
 is of alkaloidal nature, while the microbic poisons, as discovered in 
 artificial cultures, belong to the category of albuminoids and pep- 
 tones. This lack of harmony is, perhaps, clue to the fact that the 
 poisons are multifarious and that substances other than bases have 
 not sufficiently been looked for. It is possible, however, that microbes 
 act in the bodies of animals otherwise than in culture media. Finally, 
 it may be supposed that the ptomains are produced by the organism 
 itself reacting in a special maimer under the new conditions imposed 
 upon it. As a matter of fact, apparently insignificant changes suffice 
 to completely modify the physiological action of organic compounds. 
 
 Griffiths has rightly remarked that a toxic base.propylglycocyamin. 
 is found in the urine of patients suffering from various affections. 
 This base is no other than creatin, an inoffensive substance, in which 
 an atom of hydrogen has been replaced by the radical propyl. This 
 simple change has resulted in a complete transformation in the phys- 
 iological action. Klebs has reported a similar example. According 
 to him, cholera nostras is dependent upon methylguanidin, a violent 
 poison derived from guanidin, a harmless body, by substitution of a 
 group of methyl for an atom of hydrogen. 
 
 1 Roger et Gaume. Toxicite de l'eurine dans la pueurnonie. Revue de rued.. 188! 
 
1 34 IXFECTIO US DISEA SES. 
 
 It is conceivable that, in the same disease, according to a variety 
 of secondary circumstances, autointoxication may be due to various 
 substances. The results of researches have, therefore, not always 
 agreed. The toxicity of the urine varies from one patient to another. 
 In two individuals suffering from the same disease the urine of one 
 may contain alkaloids, while that of the other may be free from 
 them. 
 
 Aside from the poisons secreted by the microbes or produced under 
 their influence, there are also those arising from lack of oxidation in 
 the course of various affections. This point has been well estab- 
 lished by the researches of Dr. Albert Robin. As a result of the 
 insufficient transformation of toxic substances in the more or less 
 disturbed organs, poisons reach the kidneys in excessive quantities. 
 If these emunctories are in a normal condition, the urine eliminates 
 the noxious bodies ; if not, they are accumulated in the economy to 
 be thrown out at the time of crisis. 
 
 Rich and encouraging as are the results of researches touching the 
 question of intoxications in infectious diseases, other facts of great 
 interest are sure to be brought to light to clear up contradictions 
 and obscurities. 
 
(Ml A I'TKR V. 
 
 MICROBIC ASSOCIATIONS. 
 
 Experimental Demonstration of the Rdle of Microbic A ocial ociation of 
 
 Saprophytes wiili Anaerobic and Aerobic Microbei , M< chaniam of Microbic \ 
 (•ijit.ions." Imposition mid Criticism of Varioti Cheorii Application of Exp 
 mental Data to Clinical Medicine. Simultaneous Evolution of Two Infed 
 Successive Infections. Secondary [nfections. Cqmbined [nfections in the Skin, 
 in the Nasobuccopharyngeal Cavity, in the Respiratory Apparatus, and the 
 Alimentary Canal. Secondary Septicemias, Their Importance inthe Course and 
 in Consequence of Acute [nfections. Secondary [nfections in Chronic D 
 Favorable [nfluence of Certain Secondary [nfections. 
 
 Experimental Demonstration of the Role of Microbic Asso- 
 ciations. The analysis of clinical facts had Long demonstrated the 
 frequency of microbic associations. 1 It had boon established that, 
 in a groat number of cases, two or several bacteria simultaneously 
 or successively invaded the organism. To better comprehend the 
 signification of these clinical revelations it was necessary to transfer 
 the question upon experimental ground and discover the effects pro- 
 duced by simultaneous inoculation of two different microbes, one 
 pathogenic, the other inoffensive. This the author undertook to dr. 
 in 1889. 
 
 The author first studied the results of association of the B. pro- 
 digiosus with an anaerobic microbe, namely, with a specimen of 
 septic vibrio which was not pathogenic for the rabbit. 2 He next 
 experimented with the bacillus of symptomatic anthrax. 3 
 
 Considered as a simple saprophyte, the B. prodigiosus may be 
 injected into the muscles of a rabbit without producing any notable 
 disturbance. One or 2 ccni. of a gelatin culture are well endured. 
 While, however, this bacillus does not cause death, it does not seem 
 to be altogether harmless. 
 
 1 Hericourt. Les associations microbiennes. Revue de med.. 1887, p. 095. 
 
 2 Roger. Quelques effets des associations microbiennes. Soc. de biologie. January 
 19, 1SS9. 
 
 3 Roger. Inoculation du charbon symptomatique au lapin. First note, ibid.. February 
 2 , 1889. Second note, ibid., March 30, 1SS9. Des produits niicrobiens qui favorisent 1. 
 developpenient des infections. Compte Rendu de l'Acad. des Sc. July 29, 1889. Con- 
 tribution a l'etude experimental du charbon symptom. Rev. de med.. March 10 and 
 June 10, 1S91. 
 
136 IXFECTIO US DISEASES. 
 
 The second microbe which the author used, the bacillus of symp- 
 tomatic anthrax, is an anaerobic bacillus possessing most of the 
 characters of the septic vibrio, but no pathogenic power whatever for 
 the rabbit. It rapidly kills the guinea-pig, producing in this animal 
 the well-known lesions of gaseous gangrene. If the serous fluid of 
 a guinea-pig thus infected is inoculated into a rabbit, no disturbance 
 results. I have injected with impunity quantities varying from two 
 to ten drops. Of fifteen rabbits thus treated, none succumbed. 
 
 Here, therefore, are two microbes which, even in considerable 
 doses, give rise to no disturbance when inoculated into the rabbit. 
 
 When, however, one or two drops of the gangrenous serous exudate 
 of the guinea-pig is mixed with 0.75 c.cm. or 1 c.cm. of a culture of 
 the B. prodigiosus, and the mixture injected into the muscles of the 
 thigh of a rabbit, this animal dies in less than twenty-four hours; at 
 times in eight hours. 
 
 The necropsy reveals lesions absolutely characteristic and alto- 
 gether similar to those observed in the guinea-pig. 
 
 The microbe which had proved fatal, owing to the association of 
 the B. prodigiosus, had acquired a slight increase of virulence. The 
 serous exudate reinoculated into a second rabbit caused the death 
 of the latter, but the edema fluid of this second animal inoculated 
 into a third produced no effect. 
 
 In a second series of researches the author employed as auxiliary 
 agents other microbes than the B. prodigiosus. It is readily under- 
 stood that the field of these experiments was limited, for the author 
 could not employ those bacteria the inoculation of which was fatal 
 to the animal. Hence, the pyogenic agents were chosen for the 
 purposes of the research, and first the staphylococcus aureus, the 
 most widely distributed of all. The specimen employed was derived 
 from a furuncle, and was not very virulent. It was found necessary 
 to inject 0.6 c.cm. of a completely liquefied gelatin culture with 
 0.02 c.cm. of symptomatic anthrax in order to overcome the resist- 
 ance of the rabbit. When the same amount of staphylococcus was 
 injected alone a large abscess was the result, which healed after 
 spontaneous rupture. 
 
 The bacillus proteus vulgaris proved more active. The injection 
 of 0.25 c.cm. of a liquefied gelatin culture sufficed for the develop- 
 ment of symptomatic anthrax. 
 
 Finally, the pyogenic streptococcus was experimented with. In 
 this case, however, the addition of 1 c.cm. of a bouillon culture to 
 
MIOBOBIO ASSOCIATIONS. 137 
 
 0.02 com. of symptomatic anthrax culture wa followed by do 
 symptoms. 
 
 It is hardly necessary to say thai no absolute value Bhould be 
 placed upon these results. The action of the auxiliary microbe musl 
 vary with the specimen employed. However, the experiments above 
 reported suffice to establish the synergic rdle of two microbes. In 
 other words, it demonstrates thai two bacteria which are harmlese 
 for the animal when taken separately, become pathogenic and rapidly 
 produce dc:dh when they co-operate. 
 
 Microbic Products Favorable to Infection. Lei us now en- 
 deavor to enter a little deeper in this resc-ireli ,'iinl poinl out the 
 mechanism set at work by the auxiliary microbes in order to bring 
 about the development of a virulent disease in an animal naturally 
 immune. 
 
 To explain the action of auxiliary microbes two hypotheses may 
 be advanced: (1) The microbes may be supposed to act as living 
 elements by some mechanical action, or by appropriating nutritive 
 substances and oxygen destined for the tissues, thus weakening the 
 resistance of the latter. (2) It may be assumed that the microbes 
 secrete chemical substances which locally alter the muscles or, being 
 absorbed, disturb the general state of the invaded organism. 
 
 The idea that the auxiliary microbes act by soluble products is in 
 harmony with the results obtained in various infections. The author, 
 therefore, first attempted to verify the accuracy of this hypothesis. 
 For this purpose it was evidently sufficient to inject into the muscles 
 a mixture of symptomatic anthrax and a certain amount of a culture 
 deprived of living microbes. To secure the latter the author steril- 
 ized the fluids by heat. By employing a culture of B. prodigi<>>u* 
 which was kept for ten minutes in the autoclave at a temperature 
 of 219.2° F. (104° C), he noticed that the fluid thus prepared acted 
 like the living culture. It was only necessary to employ a little 
 more of the sterilized culture, namely, 1 c.cm. to 1.5 com. This 
 partial weakening of the fluid was to be expected. Aside from 
 the alterations which heat may produce in the active substance, 
 account is to be taken of the products secreted by the living microbe 
 when developing the muscular tissue. 
 
 Similar results were obtained with sterilized cultures of proteus 
 and of staphylococcus. It was found necessary to employ, on an 
 average, 0.5 c.cm. of the former and 1 c.cm. of the latter. 
 
 The immunity of the rabbit from symptomatic anthrax may be 
 
138 IXFECTIO US DISEASES. 
 
 strengthened by injecting into its veins a few drops of anthrax serous 
 exudate. As soon as this is done the animal becomes refractory 
 against the microbic association. Rabbits which had received two 
 injections at an interval of eight days were inoculated a week after 
 with the two microbes. They resisted perfectly. A few of them 
 presented only a local lesion. The thigh became edematous; then, 
 a few days later, the swelling subsided. In a certain number of cases 
 an abscess was formed which soon healed spontaneously. 
 
 The author then made an attempt to vaccinate the animals against 
 the effects of the microbic association bj r previously inoculating them 
 with the other microbe — i. e., the B. prodigiosus. Living or sterilized 
 cultures were repeatedly injected beneath the skin or into the veins. 
 The results were always negative in so far as the animals died when 
 they were subsequently inoculated with the two microbes. 
 
 These various results prove to what extent the experimenter is 
 able to vary morbid aptitudes. The rabbit is by nature immune 
 from symptomatic anthrax. If, along with the virus, the soluble 
 substances secreted by another microbe be introduced, the disease 
 is surely contracted. If, however, an intravenous injection of 
 anthrax virus is previously made so as to reinforce the natural 
 immunity, the animal is protected against the effects of the microbic 
 association. 
 
 The rabbit is not the only animal whose immunity may be over- 
 come by means of microbic associations. The results, as experi- 
 ments have shown the author, are similar when the pigeon is operated 
 upon, which is also, as is known, refractory to symptomatic anthrax. 
 
 Examples of Microbic Associations. The bacillus of sympto- 
 matic anthrax is an anaerobic agent to which that of tetanus may 
 naturally be compared. Therefore, the study of microbic associa- 
 tions might well be resumed with this microbe. That is what Drs. 
 Vaillard, Vincent, and Rouget have done. 1 
 
 Experimenters first recognized that cultures of the tetanus bacillus 
 injected into an animal not very sensitive to this infection — viz., the 
 rabbit — produces a fatal disease if a small amount of B. prodigiosus 
 is at the same time introduced. Extending experimental analysis 
 further, investigators established that the spores of tetanus are 
 incapable of germinating in a living organism or of giving rise to the 
 
 1 Vaillard et Vincent. Contribution a l'etude du tetanos. Ann. de PInst. Pasteur, 
 January, 1891. Vaillard et Rouget, Contribution a l'etude du t6tanos. Ibid., June, 1892 . 
 Note au sujet de l'etiologie du tetanos. Ibid., November, 1893. 
 
MKJIIOIUC ASSOCIATIONS. 139 
 
 slightest disturbance. The culture produce symptom because 
 the soluble products contained in it, and not by virtue of the figurate 
 elements. The soluble substances act rapidly and induce a fatal 
 intoxication. If care; is taken to wash ;ill Loxic product from the 
 spores, their injection produces no effect. II, however, ;i small 
 amount of a living culture of />'. prodigiosus is injected ;ii the same 
 lime, tetanus develops. Under natural conditions the phenomena 
 .•ire analogous: the leianus s|>ores enter contused i is mes or penet rate 
 along with common bacteria, which promote their development. All 
 microbes, however, are not capable of playing I he pari of an auxiliary. 
 The bacillus of Friedlaender, (he slaphylocoeeus aureus, i 1m- trep- 
 tococcus, and />'. suhli/is ha,ve remained withoul effeet. 
 
 Since the first publication of the researches on microbic associa- 
 tions the question has been pursued by ;i very greal number of 
 experimenters, among whom may especially be mentioned Blach- 
 stein, Zumpf, and Metchnikoff, on microbic associations in cholera; 
 Sanarelli on the role of the colon bacillus in the development of 
 typhoid infection; Mosny on the influence of the soluble producl 
 staphylococcus in the production of pneumonia, and Feltz, who 
 demonstrated that the toxins of the colon bacillus increase the viru- 
 lence of the bacillus anthracis and of the staphylococcus aureus. 
 
 Favorable Influence of Certain Microbic Associations. Although 
 in the majority of cases microbic associations considerably aggravate 
 the prognosis of infections, the reverse may also be observed. One 
 microbe may hinder the evolution of another, and the organism finds 
 an unexpected ally in one of the two pathogenic agents. 
 
 The starting point of researches upon this subject was the work 
 of Emmerich, who declared that guinea-pigs which had resisted an 
 inoculation of streptococcus became refractory to anthrax. Six 
 hours after subcutaneous injection into a guinea-pig thus prepared 
 the anthrax bacteria were altered. At the end of twelve or seven- 
 teen hours they were destroyed. 
 
 Taking up this research, Pawlowsky noticed that previous or 
 simultaneous inoculations of either pneumobacillus, streptococcus, 
 or, particularly, staphylococcus, arrested the development of anthrax. 
 While, however, these microbes confer immunity against subcuta- 
 neous inoculations of anthrax, they are far less powerful against 
 intravenous inoculations. By injecting two microbes, one after the 
 other, into the veins, death may be delayed, but the animals are not 
 saved. These interesting facts have been confirmed by further 
 
1 40 IXFECTIO US DISEASES. 
 
 researches. In the experiments of Pavone guinea-pigs which had 
 previously been injected with typhoid bacilli resisted anthrax infec- 
 tion. 
 
 To explain the mode of action of microbes which prevent infection 
 the theory of antagonism of bacteria has been proposed. 
 
 Pasteur had long recognized the importance of studying the devel- 
 opment of two or more microbes in the same medium. In 1SS7 he 
 pointed out that the bacillus anthracis hardly develops in a bouillon 
 which has been used for the culture of the bacillus of chicken cholera. 
 
 These observations, however, were not conclusive. Garre was one 
 of the first to undertake systematic researches upon this interesting 
 question. He discovered that culture media which are exhausted 
 by the vegetation of a microbe are unfit for the development of 
 other bacteria. The exactness of this result has been recognized by 
 various experimenters. On the other hand, it has long been known 
 that when various microbes are cultivated in the same medium, a sort 
 of struggle for existence takes place among them. Some die ; others 
 survive. If successive cultures are made, the same competition 
 occurs, and finally, only one species remains in the culture. This 
 is an instance of true natural selection. The most resistant species 
 is, as a rule, the one most widely distributed and the least pathogenic. 
 Such, however, is not always the case. One bacterium may favor 
 the development of another. An aerobic microbe, by appropriating 
 the oxygen, may aid the multiplication of an anaerobic bacterium. 
 When, however, associated vegetation is possible, modifications in 
 the chromogenic, toxicogenic, and pathogenic functions may occur. 
 The toxin of tetanus, for instance, increases the virulence of certain 
 pathogenic microbes (Roncali, Klein). The streptococcus causes 
 the diphtheria bacillus to secrete a greater amount of toxin (von 
 Schreider) . 
 
 Mechanism of Microbic Associations ; Exposition and Criticism 
 of Different Theories. Do the various results above described 
 enlighten us as to the key of microbic associations? Can it be 
 assumed, for instance, that a microbe hinders or favors an infection 
 because it produces substances which are harmful or favorable to the 
 pathogenic agent? This doctrine has been advocated by some, but 
 it seems to me unacceptable. It is contradicted by the results 
 obtained by studying the association of sterilized cultures of B. 
 jsrodigiosus with bacillus anthracis or with the bacillus of sympto- 
 matic anthrax. By injecting beneath the skin of the ear of a rabbit 
 
MIOBOBIO ASSOCIATIONS. ] 11 
 
 a mixture of 0.01 c.cm. of a cull ure of bacillu, anihraeU and 0.5 c.cm. 
 of a culture of the B. prodigiosus sterilized ai 230° F. (110° C 
 local lesion characterized by swelling, redness, and heal , occur , The 
 control animals inoculated with pure anthrax presenl a little edema 
 without redness or heat, and succumb from the second to the fifth i 
 The others survive the inoculation and die later than the controls. 1 
 
 The resisting animals have doI become immime. They die when 
 they are subsequently reinoculated beneath the skin of the ear. A 
 special phenomenon only is produced, namely, an enormous ed 
 invading Hie eyes, the cheeks, the forehead, and gh ing a very strange 
 aspect to the face. 
 
 If the same experiments are repeated upon guinea-pigs, diamet- 
 rically contrary results are obtained. The animals which receive the 
 mixture of anthrax and B. prodigiosus present early and very exten- 
 sive edemas and succumb several days before the controls. The 
 differences are quite clear when cultures of low virulence, permitting 
 a sufficiently long survival are employed. The effects are identical 
 whether the B. prodigiosus be injected into the same point where 
 the anthrax is or into a different region. 
 
 Reciprocally, Deuschmann has shown that the B. prodigiosus, 
 which facilitates the development of symptomatic anthrax in the 
 rabbit, exerts a contrary action upon the guinea-pig. While it 
 abolishes the immunity of the refractory animal, it enables the 
 animal which is naturally susceptible to resist a virulent inoculation. 
 
 These facts again demonstrate how hazardous it is to jump to 
 generalizations. They are also of special interest because they serve 
 to disprove all the theories offered in explanation of the mechanism 
 of microbic associations. 
 
 These theories are already very numerous. They call to their aid 
 either modifications of diapedesis or of phagocytosis, or an action 
 of microbic toxins upon the pathogenic agent. According to Drs. 
 Vaillard and Vincent, who have studied the adjuvant action of living 
 cultures of the B. prodigiosus upon tetanus, the phagocytes are busy 
 incorporating the saprophyte bacilli, and, while they are engaged in 
 this easy pursuit, the tetanus bacillus has time to develop and to 
 secrete its toxins. This view was no longer tenable after Drs. Vail- 
 lard and Rouget recognized that the soluble products acted like the 
 virulent cultures. They then were led to modify then* theory and 
 
 1 Roger. Influence des produits solubles du R. prodigiosus sur 1 'infection charbon- 
 neuse. Soc. de biologie. May 10, 1S05. 
 
142 INFECTIOUS DISEASES. 
 
 argue that the microbic products exert a chemiotactic action. These 
 products possess the double property of attracting the leucocytes and 
 of necrosing them. 
 
 According to Prof. Bouchard, the toxins act by influencing the 
 vasomotor centres. According as they favor or hinder reflex vaso- 
 dilatation, they favor or hinder diapedesis and phagocytosis and, 
 consequently, assist the organism or, on the contrary, the microbe. 
 Among others, the following objection is to be made against this 
 theory: In order to paralyze the vasomotor centres, considerable 
 quantities of toxin must be introduced ; in order to produce infection 
 the injection of a fraction of a drop suffices. What is, however, still 
 more grave is the fact that this theory, as well as that of Vaillard, 
 does not explain the variability of results obtained according to the 
 species operated upon and the microbe employed. If the B. pro- 
 digiosus prevents phagocytosis when it is associated with tetanus or 
 with symptomatic anthrax, why does it favor phagocytosis when it 
 is combined with the bacillus anthracisf 
 
 If, on the contrary, it be admitted that microbic toxins act by 
 modifying the germicidal power of the blood, it is plain that the 
 supervening changes may inhibit one species of bacteria and favor 
 the action of another. I recognize that my explication is no more 
 than a hypothesis needing experimental control. However, it is 
 supported by some facts. According to Nissen, the germicidal power 
 of the blood is abolished when a sufficiently large amount of microbes 
 is injected into the veins. Bastin, after confirming Nissen's discovery, 
 obtained analogous results by employing cultures sterilized by means 
 of heat, chloroform, or ether. He further established that there is 
 a relationship between the dose injected and the degree of diminution 
 of the germicidal power. Lastly, he has pointed out that when the 
 germicidal power is abolished for one species, say for the staphylo- 
 coccus aureus, it may be so with regard to another, the B. lactis 
 aerogenes, for instance. If it is some day recognized that the ger- 
 micidal power is increased for certain agents, the demonstration will 
 be perfect. For the time being, however, the explanation presented 
 by us is only an hypothesis, but it is the only one in accord with the 
 results thus far obtained by experimentation. 
 
 Clinical Study — Combined Infections. 
 
 Clinical observation first led to experimental researches on microbic 
 associations. In its turn, experimentation sheds light upon facts 
 
MICROBIC ASSOCIATIONS. I I.; 
 
 observed in the sick and enables us to comprehend bhemechani m of 
 
 combined infections. 
 There are four orders of facts to be considered: 
 
 1. Two exogenous infections evolving simultaneously in the Bame 
 subject. 
 
 2. Two infections evolving successively. 
 
 3. An acute infection attacks an individual who has previously 
 suffered from a chronic infection. 
 
 4. An intercurrenl infection favors the developmenl of pathogenic 
 germs which, until then, vegetated withoul any inconvenience upon 
 the skin and mucous membranes. This last group is, perhaps, the 
 most important of all. 
 
 Simultaneous Occurrence of Two Infections. When two infec- 
 tions develop simultaneously, they evolve side by side, each preserv- 
 ing its special characters. An aggravation in their evolution may 
 sometimes be observed. Even then, however, the two proa 
 remain distinct. Such is the case, for instance, when two eruptive 
 fevers develop in the same individual. In most cases, measles and 
 scarlatina coexist. The two eruptions may appear at the same time, 
 each developing at points of the skin which have been spared by the 
 other. Each disease behaves as if it were alone, except that, in many 
 cases, the eruptions last for a shorter time than usual. The prog- 
 nosis is in nowise modified. 
 
 We cannot dwell upon all possible combinations. Variola, scar- 
 latina, vaccinia, typhoid fever, and whooping-cough may occur one 
 with another. Measles may coexist with whooping-cough, typhoid 
 fever with pneumonia, and, in hot countries, with malaria, and, 
 though very seldom, even with tuberculosis. 
 
 In its various stages, syphilis may be associated with other infec- 
 tions. At the start it may be a "mixed chancre."' resulting from 
 the simultaneous inoculation of the syphilitic virus and that of soft 
 chancre. In these cases, the soft chancre, the period of inoculation 
 of which is shorter, appears first. A few days after its base becomes 
 hard, then the soft chancre is healed while the syphilitic lesion per- 
 sists. The chancre is, therefore, mixed but for the middle period 
 of its existence. A similar evolution occurs in vaccinosyphilitic 
 chancre. The vaccinal eruption appears and runs its regular course. 
 Afterward, toward the twenty-fifth day, the chancre makes its 
 appearance beneath the crusts of even the cicatrices of the pustules. 
 At a more advanced stage, syphilis may coexist with tuberculosis. 
 
144 IXFECTIO US DISEA SES. 
 
 The result is hybrid clinical types and events difficult of interpre- 
 tation. 
 
 Secondary Infections. The author has several times seen patients 
 convalescent from one eruptive fever contract another. The second 
 infection generally runs its regular course. More interesting are 
 those cases in which diphtheria makes its appearance in the course 
 of another disease, especially of scarlatina or measles. It is then a 
 question whether this secondary diphtheria is really due to an addi- 
 tional infection from without or whether, on the contrary, it is 
 dependent upon exaltation of the Loeffler bacillus already present 
 in the throat as an innocent resident. Without absolutely rejecting 
 the latter interpretation, I believe the former is true in the majority 
 of cases, if not in all. Out of a total of 4030 patients affected with 
 scarlet fever or measles that have been treated in my wards, only 
 one case of secondary diphtheria was observed. This was in a woman 
 who had been in a ward close to one where diphtheria cases were 
 treated. It is well to recall that diphtheritic manifestations which, 
 until a few years ago, were of frequent occurrence in hospitals for 
 children, have become altogether rare since prophylactic measures 
 and isolation of different classes of patients has been rigorously 
 practised. It is, therefore, not unfair to conclude that secondary 
 diphtheria originates by contagion. 
 
 Development of tuberculous manifestations subsequent to an acute 
 infection is not rare. In most cases the course is rapid. At times 
 the process is one of caseous pneumonia. More often, however, 
 tubercles invade the whole organism. 
 
 Typhoid fever is not rare in consumptives. It runs its course in 
 a regular manner. Subsequently, however, tuberculosis assumes an 
 acute course. 
 
 The influence of erysipelas is more complex. Its influence on 
 pulmonary tuberculosis is never favorable, and is at times harmful. 
 As to its action upon local tuberculosis, principally upon lupus, opin- 
 ion is divided because, perhaps, the results are variable. Erysipelas 
 developing in an old lesion favors its cicatrization. It may likewise 
 cause improvement in neoplasms, epitheliomata, and, above all, 
 sarcomata. It acts in the same way in lymphadenia. 
 
 It may, therefore, be concluded that while, in the majority of 
 instances, an intercurrent acute infection aggravates a pre-existing 
 chronic infection, it may, in some cases, favor the healing of some 
 atonic lesions. 
 
MICBOBIO ASSOCIATIONS. 1 j:, 
 
 Combined Infections of the Skin. In the majority of disei 
 affecting the skin or the mucous membrane communicating with 
 the exterior, mixed infection is unavoidable, and il i often difficult 
 to determine the part due to the main agenl and thai ascribable to 
 auxiliary agents. 
 
 The role of secondary infections is of considerable importance in 
 cases of variola. The pustules contain a greal number of pyogenic 
 microbes From cutaneous sources. When the patienl dies thestaphy- 
 lococcus, and particularly the streptococcus, and al times the pneu- 
 mococcus, are found in Hie organs. The question is to ascertain the 
 respective r61e of the specific agenl and of the secondary microbes. 
 Is it not to the latter thai the fatal termination is due? And can 
 it not be assumed that the gravity of confluent variola depends 
 mostly upon the extent of suppuration, absorption of secreted prod- 
 ucts in the pustules, and general infection of the organism by pu- 
 cocci? It is evidently impossible to precisely answer this question. 
 All that can be said is that the microbe of smallpox is a genuine pus 
 coccus, but one of special nature, since it produces pus particularly 
 rich in mononuclear leucocytes. This fact authorizes us to limit the 
 role of superadded agents. Clinical observation already pointed to 
 this conclusion, for according as the subject is or is not partially 
 immune — according, for instance, as his organism has or has not been 
 modified by previous vaccination — suppuration runs its course or is 
 cut short. Notwithstanding the presence of pus cocci in the pustules. 
 the eruption is aborted. 
 
 Combined Infections in the Throat. What has just been said 
 concerning the skin may be repeated with regard to mucous mem- 
 branes. In this connection, scarlatina is the most interesting infec- 
 tion. Under its influence the streptococcus of the mouth becomes 
 exalted and plays an important part in the genesis of early or tardy 
 angina, of local complications, such as purulent coryza. abscess 
 the tonsils, adenophlegmon^ of the neck, or of complications in 
 distant parts, such as nephritis. The presence of the streptococcus 
 in the various complications observable in the course of scarlatina 
 is so constant that certain authorities consider this microbe not a 
 superadded agent but the actual cause of the malady. This opinion 
 is not yet supported by absolutely convincing evidence. The case 
 of Heubner, everywhere cited, who developed erysipelas as a result 
 of having received in his face salivary particles from a scarlatina 
 patient, demonstrates the exaltation of the microbe, but by no means 
 
 10 
 
146 IXFECTIO US DISEASES. 
 
 its specific role. There exist a few observations of patients conva- 
 lescent from scarlatina who were attacked by erysipelas. The devel- 
 opment of the dermitis without any contamination is another proof 
 of the role played by the streptococcus, for facts of this sort, of which 
 I have collected nine examples, are much rarer after other infections. 
 As there is no absolute demonstration that the streptococcus is the 
 cause of scarlatina, we may conclude that this microbe becomes 
 exalted under the influence of an angina, and thus becomes capable 
 of giving rise to various complications. 
 
 Similar considerations may be presented with regard to all affec- 
 tions of the throat. In cases of diphtheria, for instance, a great 
 number of microbes are found in the false membranes. It is quite 
 evident that there can be no pure diphtheritic angina. In order to 
 be convinced of this fact, it will suffice to make a direct examination 
 of the false membranes or to sow them on agar-agar. Microbic asso- 
 ciations will always be found. Angina appears to be pure only when 
 the cultures are made in serum. This medium being more favorable 
 to the bacillus of Loeffler than to other microbes, the specific agent 
 is the first to develop. Is it right, however, to conclude that the 
 other bacteria are indifferent because they vegetate slowly or not 
 at all in this medium ? The tetragenus, for instance, is frequently 
 encountered in anginas, whether diphtheritic or otherwise. It is 
 seldom noted, because it develops poorly in serum; other culture 
 media are required. Therefore, the questions put in reference to 
 tetanus and gaseous gangrene may be asked with regard to diph- 
 theria: Is the bacillus of Loeffler capable of developing alone? Is 
 it not rather necessary that it should be assisted by common bacteria, 
 the common pus cocci of the throat which prepare the soil for it? 
 
 In 193 cases of sore throat, 31 of which were diphtheritic, 46 non- 
 diphtheritic, 116 scarlatinal, we made bacteriological researches on 
 serum, on agar-agar, and by direct examinations. The results varied 
 considerably with the modes of examination and the culture media. 
 The fact is that all microbes have not the same aptitude to develop 
 in such and such a medium. The exclusive presence of the bacillus 
 of Loeffler upon a serum tube simply indicates that this bacillus 
 possessed a great aptitude to vegetate in this medium and that its 
 rapid development checked and prevented the multiplication of the 
 other bacteria. Let another culture medium be employed, and the 
 results may be entirely different. The following table may give an 
 idea of this fact: 
 
MIOBOBIO ASSOCIATIONS. I 17 
 
 SuMMun of Seventh seven Comparative Obbebvatio 01 Seri i 
 
 Cim.i LTRES PROM A BTGIM ah, 
 
 Diphtheritic Non-diphtheritic .. , . _„ , 
 
 anginas, ■• I 00 . aT^tno . to 00 
 
 Serum. Agai Serum. Agm vm, Agar. 
 
 Bacillus of Loeffler :;i L8 . . 31 16 
 
 Streptococcus 3 L6 25 ! -n 
 
 Tetraoocous 5 17 12 32 17 10 
 
 Staphylococcus I 2 fj 5 7 7 
 
 Pneumococcua I *; _' <i 
 
 Oidium 2 . . I 
 
 B. suhlilis . . l l I I 
 
 Undetermined cocci 3 2 7 2 10 4 
 
 Undetermined bacilli 1 2 10 L3 L5 I". 
 
 Filaments I :: 2 
 
 Spirilla . . 1 1 1 1 
 
 From the mouth mid nasal fossa 1 microbes may enter the sinuses 
 of the face, the salivary glands, and the middle ear by way of the 
 Eustachian tube. The mouth seems to be even constantly inn 
 in certain diseases like measles. The microbes, however, remain in 
 a harmless state and give rise to no disturbance. 
 
 Combined Infections in the Respiratory Apparatus. Among the 
 microbes frequently encountered in the saliva of healthy individuals 
 there is one which, with the streptococcus and staphylococcus, plays 
 a very important part in the development of secondary infections — 
 viz., the pneumococcus. This microbe often becomes virulent in 
 the course of the most varied infections and, notably, in erysipelas. 
 It may produce various inflammatory lesions in the mouth. It must 
 arrest our attention, however, on account of the complications which 
 it may cause in the organs of respiration. It is known that it is the 
 most frequent agent of the various thoracic complications of infec- 
 tious diseases. The streptococcus, its companion in the buccal 
 cavity, comes next. Among the bacteria of most frequent occur- 
 rence, we may also mention the micrococcus tetragenus, staphylo- 
 coccus, pneumobacillus, colon bacillus, etc. 
 
 It may well be asked how these germs are able to invade the re- 
 spiratory apparatus. The majority of authors believe that they are 
 driven from the buccal cavity toward the lower respiratory passages. 
 In a highly interesting work, Dr. Beco 1 opposes this view. Taking 
 ground upon the fact that pathogenic species are encountered in 
 lungs free from all apparent morphological alteration, and that these 
 
 1 Beco. Recherches sur la flore bacterieniie du poumon de l'homme et des animaux. 
 Arch, de m£d. exper., 1S99, p. 317. 
 
148 INFECTIOUS DISEASES. 
 
 are the microbes which most frequently give rise to bronchopulmon- 
 ary infections, he concludes that the germs were already present in 
 the lungs, and had only to develop. 
 
 The argument is not convincing, however. The pneumococcus has 
 been encountered in the lungs, but the researches were made on 
 cadavers. It is therefore a question whether the microbe had not 
 penetrated during the agony or the ten or twelve hours which passed 
 between the moment of death and that of cultivation. This remark 
 is supported by the fact that in two out of four cases of sudden death 
 the lungs were found sterile. If, on the other hand, account is taken 
 of researches pursued on animals, the conclusion is reached that the 
 presence of the pneumococcus in the lung is exceptional. We con- 
 tinue, therefore, to believe that bronchopulmonary infections occur- 
 ring in the course of diseases are, as a rule, due to buccal germs. 
 The latter may be carried clown with particles of saliva, or be dis- 
 lodged by the current of air passing over the dried mucous membrane. 
 Although microbes cannot be carried away by the inspired air when 
 they are surrounded by fluid, conditions are changed when, under 
 the influence of the primary disease, the secretions are scanty and 
 the mouth covered with soot. 
 
 Whatever may be the mechanism governing their development, 
 the secondary infections of the lung are generally due to the pneu- 
 mococcus. This is true in cases of eruptive fevers, in diphtheria, 
 typhoid fever, and even in erysipelas. It might be believed that in 
 the last-named disease the pulmonary complication depended upon 
 the streptococcus, that it was a case of pulmonary erysipelas. Such 
 was the old view. It is, however, established at present that the 
 streptococcus has no tendency to leave the skin. The pulmonary 
 lesion is the result of secondary infection, depending upon the pneu- 
 mococcus. 
 
 Combined Infections in the Alimentary Canal. Microbic associa- 
 tions are likewise constant in the digestive organs. Experimental 
 researches have demonstrated their importance in typhoid fever and 
 cholera. 
 
 With reference to cholera, the researches of Metchnikoff have well 
 shown the auxiliary role of ingested bacilli and at the same time 
 explained the resistance of certain persons and the immunity of 
 certain regions. Sanarelli admits an analogous etiology for yellow 
 fever. The same pathogenesis may be claimed for amebic dysen- 
 tery. Although we admit the amebse to be the specific agents of 
 
MIOBOBIO ASSOCIATIONS. I 19 
 
 oik* form of this affection, we also believe thai an adjuvant rdle is 
 bo be attributed to the bacteria thai 3warm in the intestinal ca 
 and participate in all the morbid processes developing therein. 
 
 In most- infections digestive disl urbances appear which bring aboul 
 an increased virulence of microbes colonized iii the gastrointestinal 
 cavity. This explains the development of mucomembranous enter- 
 itis consecutive to typhoid fever. Cases of appendicitis have also 
 been mentioned as the result of the mosl varied infections. In order 
 to resist the action of exalted microbes, the lymphoid structun 
 the appendix become the seat- of an inflammatory process which is 
 comparable to that observed, under the same circumstances, in the 
 tonsils, and at times results in more or less profound lesions. 
 
 The digestive disturbances may, in their turn, act on the organism. 
 The toxins elaborated in the intestine diminish the resistance of 
 certain tissues and notably of the sebaceous glands. Hence, the 
 frequency of furuncles in cases of excessive intestinal putrefactions. 
 Both the old method of prescribing purges and the modern medica- 
 tion by antiseptics act, I believe, in the same manner. They diminish 
 fermentation, and thus suppress the cause of secondary infection. 
 
 As soon as the microbes of the mouth or of the intestine become 
 exalted, they are capable of invading the neighboring parts. Sup- 
 pression or at least alteration of the secretions favors the immigration 
 of the microbes into the organs connected with the digestive tube. 
 Ancient clinicians had long remarked that parotiditis occurred par- 
 ticularly in grave fevers when the mouth was dry and repeated 
 cleansing did not remedy the absence of secretions. These glandular 
 inflammations have become rare with the advance of individual 
 hygiene. 
 
 Secondary Septicemias. In certain cases bacteria tend to invade 
 the lymphatic or blood channels and then produce septicemic mani- 
 festations of a general character, or they become localized in some 
 organ and give rise to various inflammatory or, oftener. suppurative 
 lesions. 
 
 When common bacteria invade the organism, no matter what the 
 mode of entrance may be, three eventualities are possible: (1) In 
 some instances the secondary infection assumes the gravest aspect 
 and is expressed by a septicemia which develops without determined 
 localizations and may rapidly terminate in death. (2) In other cases 
 septicemia becomes localized in some viscus the disturbances of 
 which may be predominant in the morbid process. Finally, the germs 
 
1 50 IXFECTIO US DISEASES. 
 
 may at times be destroyed and eliminated as fast as they penetrate; 
 they may be found in the different secretions, but give rise to no 
 appreciable symptom. 
 
 There has recently been described a septicemic form of typhoid 
 fever due to secondary action of the streptococcus. This strepto- 
 typhoid infection (Vincent), studied by Loison, Simonin, Arnaud, 
 Vincent, and Wassermann, is characterized by irregularity of the 
 fever-tracing, very marked acceleration of the pulse, and tendency 
 to hemorrhages. 
 
 In certain cases septicemia is expressed by cutaneous eruptions. 
 Rubeoliform, scarlatiniform, and polymorphous erythemata have 
 been encountered in typhoid fever. In two such cases, Etienne and 
 Gillet discovered staphylococcus in the blood. 
 
 Secondary bacteriemia is at times so frequent that, without the 
 revelations of bacteriology, it would have been difficult to determine 
 its nature. Such is the case in gonorrhea. It was natural to attrib- 
 ute all the secondary manifestations to the gonococcus of Neisser 
 and conclude that this specific microbe is capable of emigrating from 
 the urethra and giving rise to symptoms in distant organs, notably 
 to arthrites. There are recorded observations in which the joints 
 contained no other microbes than the gonococcus. Such is not 
 always the case, however. It is not necessarily the gonococcus that 
 produces the so-called metastatic phenomena. In many instances 
 gonorrhea does no more than prepare the way for the entrance of 
 the microbes of suppuration, and what is found in the articulations 
 is a common pus coccus. 
 
 Septicemia may present a special aspect when it occurs at the 
 time of decline of or convalescence from an infection. In some cases 
 it is transitory, as primary septicemias sometimes are. It is even 
 possible that certain disturbances of convalescence, which are too 
 often attributed to fatigue or some error of diet, are aborted septi- 
 cemias, as traumatic fever and milk fever are abortive forms of 
 primary septicemia. 
 
 Septicemias of convalescence are often attended by more lasting 
 manifestations, general disturbances, and cutaneous or visceral 
 symptoms. The case is then one of septicemia with erythema, 
 purpura, and, in more serious instances, with albuminuria, gan- 
 grenous lesions of the skin, etc. 
 
 These septicemias may at times simulate a secondary complica- 
 tion, notably a meningitis. During the cholera epidemic of 1892 the 
 
MIOBOBIO ASSOCIATIONS. [51 
 
 author observed two cases of this kind, 1 and Dr. Siredey has pub- 
 lished some analogous reports. 2 The patients die with the appearance 
 of meningeal phenomena, withoul necropsy revealing the slightest 
 
 alteration in (he nerve centres or in their envelopes. On 'he other 
 
 hand, however, bacteriology explains the mechanism of tin- occur- 
 rences. In one of the cases above referred to, experimenting with 
 
 the cerebrospinal fluid and the liver, the author obtained pure cul- 
 tures of an unidentified bacillus. In order to indicate it- pathogenic 
 action and putrefactive power, he called it bacillus septicus putidui . 
 This microbe shall be repeatedly referred to because, on are. Hint of 
 the lesions it produces in animals and of the activity of the toxins 
 it secretes, it presents a certain interest from the standpoint of 
 general infectious pathology. 
 
 When secondary infections are somewhat prolonged they may 
 simulate a relapse. Senger, dwelling on this point, asserts That, in 
 typhoid fever, relapses are often nothing else than septicemias. The 
 intestinal ulcerations enable the other germs to do mischief which 
 is too readily ascribed to a recrudescence of the primary disease. 
 This conception deserves to be submitted to rigorous analysis, for 
 it is very ingenious and in harmony with the actual data of general 
 pathology. The humoral modifications occurring at the time of 
 recovery should prevent relapses. On the other hand, it is con- 
 ceivable that these modified humors may be inactive in the presence 
 of some new pathogenic agent. 
 
 Secondary Localizations of Septicemic Processes. "W hen common 
 bacteria invade the organism they do not always produce a general 
 septicemia. In some instances they may become localized in a 
 viscus and give rise to inflammatory or suppurative disturbances. 
 This fact raises two interesting questions: In the first place, in the 
 presence of an inflamed viscus, the question is, whether the lesion 
 is due to the primary process or to a secondary one. In the second 
 place, it is necessary to learn whether the organ has been invaded 
 by propagation or by general infection. For instance, let us suppose 
 a suppurative lesion in typhoid fever. Without a bacteriological 
 analysis it is impossible to affirm that it is a secondary lesion. G. 
 Roux has shown, for instance, that the abscesses in the spleen may 
 be dependent upon the typhoid bacillus. Valentini found no other 
 
 1 Roger. Recherches bacteriologiques sur un cas de septicemic See. de biologie. 
 Oct. 29, 1S92. Septicemic consecutive au cholera. Rev. de med.. Oct.. 1893. 
 1 Siredey. Discussion sur le cholera. Soc. med. des hop., Xov. 4. 1892. 
 
152 INFECTIOUS DISEASES. 
 
 than Eberth's bacillus in the fluid of a purulent pleurisy. Fraenkel 
 made the same statement with regard to a case of peritonitis. It 
 has recently been further established that osteomyelitis consecutive 
 to typhoid fever is often due to Eberth's bacillus. 
 
 Let us now suppose ourselves confronted by an acute nephritis 
 supervening in the course of an infection. The first question to ask 
 is whether this nephritis is ascending or hematogenic, viz., whether 
 the microbes have made their way from the bladder through the 
 ureters or whether they have reached the kidney through the blood- 
 vessels. Pathological anatomy, by discovering the existence of old 
 lesions in the bladder, and especially by pointing out the topography 
 of the renal alterations, often enables us to solve the first problem. 
 The next task is to determine whether the lesion observed is due to 
 the principal microbe or to a secondary agent. Is the most interest- 
 ing of all infectious nephrites, namely, that of scarlatina, dependent 
 upon the specific microbe or upon the superadded streptococcus 
 which is constantly found in the urine in cases of scarlatinal albu- 
 minuria? 
 
 To sum up, secondary infections, almost always due to common 
 bacteria, are frequently observed in all infectious diseases. These 
 secondary infections may be expressed by septicemias, symptoms 
 of which are confounded with those of the principal disease or which 
 impart to the primary process a peculiar character. A secondary 
 infection may be localized from the beginning or subsequently in 
 one or several viscera. Hence, a series of new manifestations occur 
 whose nature can be determined only by bacteriological researches. 
 
 It is hardly necessary to dwell upon the importance and gravity 
 of secondary infections. Whether septicemic or pyemic, general or 
 localized, they may impart to the disease a character of malignancy 
 by creating hemorrhagic forms, by giving rise to endocardites, 
 nephrites, degenerations of the liver, and by localizing themselves in 
 arteries and veins. Moreover, they may render prognosis graver. 
 If it is true, for instance, that scarlatinal nephritis is clue to a sec- 
 ondary infection, it is easily conceived that this additional infection 
 is often graver and accompanied by more disastrous consequences 
 than the primary disease. 
 
 Microbic associations, therefore, play a capital role in the develop- 
 ment of diseases. The more profoundly we study the pathogenesis 
 of infections the more clearly we recognize that adjuvant causes are 
 required for the development of a specific microbe. Among these 
 
MIOBOBIO ASSOCIATIONS. \: h \ 
 
 adjuvant causes, a principal one i : represented by the auxiliary 
 microbic agents vvliicli set the disease in motion, explain certain 
 symptoms, and cause various complications. These facts do not 
 suppress the idea of specificity. For among the microbes which 
 
 Simultaneously develop, there is one which impresses upon the di.-e;i~r: 
 
 its particular stamp, its clinical physiognomy. The other- are useful 
 or indispensable auxiliaries, but do no more than add some features 
 
 to the morbid process. 
 
CHAPTER VI. 
 
 DEFENSES AND REACTIONS OF THE ORGANISM. 
 
 Means of Defense of the Organism against Infections. Role of the Lymphatic Glands 
 and Omentum. Role of the Organs, Liver, and Lungs. Variations in the Action 
 of the Liver upon Microbes. Means of Defense against Microbic Poisons. Role 
 of the Various Organs; Role of the Liver. Modes of Elimination of Microbic 
 Poisons. Reaction of the Organism against Microbes and Toxins. Mode of 
 Production and Signification of Local Lesions. Inflammation. Production of 
 Inflammatory Exudates. Importance of Diapedesis and Phagocytosis. Evolu- 
 tion and Reparation of Inflammatory Lesions. Mode of Production and Chemical 
 Constitution of Serous Exudates. The Fibrinous Exudates and False Mem- 
 branes. 
 
 The Defenses of the Organism against Infections. 
 
 When a pathogenic microbe attacks at any point of the organism, 
 two events are possible : First, the microbe may be highly virulent 
 or the organism in a weakened state. Consequently, no struggle 
 takes place, there being no resistance on the part of the organism. 
 The result is a general infection. Secondly, the invaded organism 
 reacts and endeavors to arrest the invader or to circumscribe the 
 infection. A local reaction is then produced characterized by an 
 afflux of serum and leucocytes. In some instances the first barrier 
 thus created suffices to kill the microbe, and the local lesion thus saves 
 the economy. 
 
 Unfortunately, the latter is not always the case. The microbes 
 too often overcome the first line of defense and gain entrance into 
 the circulation. 
 
 Protective Role of the Lymphatic Glands and Omentum. If the 
 microbes pass into the lymphatic vessels they may be arrested in 
 the lymphatic glands. The interesting researches of Bezancon and 
 Labbe and of Manfredi conclusively demonstrate the important role 
 of these glands as defensive organs. This fact had been already 
 indicated by clinical observation. In the course of the most varied 
 infections, acute, subacute, or chronic inflammations, the glands 
 corresponding to the affected regions swell, and inflammation is at 
 times so intense as to present the appearance of spreading in the 
 form of periganglionic edema. 
 
DKFFNSFS AND llEAOTIONB OF THE ORGANISM. \.„, 
 
 In spile of their simple appearance, adenopathie may nun,. 
 special characters corresponding to the nature of the primary focus. 
 The glands become indurated in cases oi syphilitic chancre; they 
 suppurate; and become ulcerated in the case of sofl chancre; they 
 are ensealed in tuberculosis, etc, However, adenopathies . especially 
 in their first stage, must be considered as defensive reactions. Man- 
 fred] lias demonstrated that the microbes during their sojourn in 
 the glands lose part of their virulence, thai is, they become atten- 
 uated. 
 
 These considerations regarding I lie rdle of the lymphatic gland- 
 lead to the question whether other parts of the organism similar in 
 structure can play the same defensive role. Anatomists have come 
 to consider the serous membranes as adne\:e of the lymphatic sys- 
 tem. Let us consider the peritoneum, for example. 1 Since the 
 investigations of Ranvier the greater omentum is regarded as an 
 extended lymphatic gland. Histological researches have shown 
 that the cells contained in this portion of the serous mem- 
 brane actively proliferate when a more or less virulent microbe is 
 introduced into the abdominal cavity. When a moderately virulent 
 culture, for instance, a culture of staphylococcus aureus, is injected 
 .beneath the skin, this culture gives rise to extensive suppuration; 
 but when the same amount is introduced into the peritoneum, no 
 symptoms are observed. This fact demonstrates, contrary to what 
 was once believed, that a healthy serous membrane resists infection 
 better than does the subcutaneous cellular tissue. It must be noted, 
 however, that the animal which thus presents no disturbance shows 
 some modifications in the greater omentum, because the inoculated 
 microbes pass from the peritoneum to the greater omentum. When 
 small foreign bodies are introduced into the peritoneum, most of 
 them are gradually pushed by the intestinal movements toward the 
 greater omentum and there become localized. 
 
 It may, therefore, be concluded that the greater omentum plays 
 an important role in the protection of the peritoneum. Experiments 
 have shown that its extirpation does not altogether abolish, but only 
 weakens, the resistance of the peritoneum which, while sufficient to 
 prevent infection of the organism by greatly attenuated microbes, 
 is no longer strong enough to resist virulent microbes. 
 
 There are three defensive barriers opposed to the exalted microbes 
 
 1 Roger. Role protecteur du grand epiploon. Soc. de biologie. Feb. 19, 1S9S. 
 
lo6 INFECTIOUS DISEASES. 
 
 of the digestive tract. While these agents tend to pass through the 
 intestinal walls, they meet numerous lymphoid structures which 
 hinder their progress. Should they overcome this first line of de- 
 fense they. may enter the chyliferous vessels, but they are then 
 arrested by the mesenteric ganglia. If they enter the portal vein 
 they meet the liver, which, as will presently be shown, is capable of 
 arresting and destroying them. If they succeed in penetrating the 
 intestinal walls, as is the case especially in young children, they are 
 rapidly destroyed in the peritoneum, the protective role of which 
 depends chiefly upon the greater omentum. 
 
 Protective Role of the Liver and Lungs. 1 When microbes pene- 
 trate by way of the stomach or intestine they pass into the portal 
 vein and traverse successively the liver, the right heart, the lungs, 
 and the left heart, to be thrown thence into the general circulation. 
 In all other cases they first encounter the lungs. 
 
 Whatever their mode of penetration may be, microbes that have 
 reached the blood rapidly disappear from the main bloodvessels. At 
 the end of ten or fifteen minutes they are no longer found in this 
 location, even though intravenous inoculation has been practised. 
 The blood, then, represents an inhospitable medium for bacteria, 
 which must abandon it and take refuge in the capillaries of the organs. 
 Here the struggle between the organism and the pathogenic agents 
 is carried on. The latter begin to multiply and secrete toxic sub- 
 stances which may insure them victory, while the cells of the body 
 endeavor to exert their protective role, either by producing germicidal 
 or antitoxic substances, or by taking up and digesting the microbes. 
 
 Two hypotheses are possible: Firstly, it may be assumed that the 
 various phases of the struggle are alike in all the capillaries. Either 
 the microbe or the organism will triumph, and the ultimate result 
 will be the sum of the partial results of the same character. Or, 
 secondly, it may be supposed that the phenomena vary from one 
 capillary network to another; that the effects of the struggle are not 
 identical in all the organs, but in some of them the microbe is victo- 
 rious, in others the cell. If so, the events become more complex. 
 The final result will be the sum of the partial results of different 
 characters. 
 
 1 Roger. Sur le role protecteur du foie coutre l'infection charbonneuse. Soc. de 
 biologie, Oct. 9, 1S97. Les organes protecteurs coutre les infections. Presse med., 
 June 15, 1898. Le role du foie dans les infections. Presse m£d., Dec. 21, 1898. Le role 
 protecteur du foie et du poumon. Cinquantenaire de la soc. de biol., Dec. 27, 1899. 
 
DEFENSES A Nl> I! EA < 'TIONB <> F 'I'll E <> BO A NISM, \ :,~ 
 
 These theoretical considerations lead to Hi'' que 'i<>n whether 
 differences occur in the evolution <>l infection di ea e accordii 
 the vessel by which the culture is introduced. Experimenters gen- 
 erally inject the microbes through some peripheral vein. The patho- 
 genic agent then first pusses through the capillaries of the lung, to 
 subsequently reach the general circulation. I havethough.1 that the 
 virulent injections should be practised through five differenl chan- 
 nels. 
 
 The author made inoculations by the distal end of the common 
 carotid artery in order to determine the rdle of the cerebral capil- 
 laries; by the distal end of the femoral artery, in order to study the 
 influence of a more common network ; by a branch of the portal vein, 
 to study the action of the liver; by a peripheral vein, to learn the 
 role of the lungs, and, finally, by the central end of the aorta (central 
 end of the carotid artery). 
 
 In making these injections care should be taken not to produce 
 any local lesion at the point of injection and not to use cultures of 
 too great virulence. The evolution of a local lesion would confuse 
 the results, and the capillary networks would prove insufficient 
 barriers against a culture of too great energy, so that the microbes 
 would rapidly pass through them and produce a general infection, 
 evolving in the same manner, irrespective of the mode of entrance. 
 
 The microbes employed by the author were the bacillus anthracis, 
 the staphylococcus aureus, the streptococcus of erysipelas, the colon 
 bacillus, and, finally, a more highly organized parasite, oidium albi- 
 cans. 
 
 The animals which received the virus of anthrax by the aorta 
 succumbed first. Those which were injected through some periph- 
 eral vein survived somewhat longer, which indicates a slight pro- 
 tective action of the lungs. This action, however, was not noticeable 
 when more energetic cultures were employed. The injections prac- 
 tised through the carotid artery permit a somewhat longer survival 
 than the intravenous inoculations. This result is interesting, as it 
 leads to the belief that the nerve centres are capable of hindering 
 anthrax infection. 
 
 It is to be recognized, however, that the differences observed 
 according to the vessel by which the anthrax virus is injected have 
 so far been of little consequence. While a few animals resist a little 
 longer than others, all succumb. The twenty animals which the 
 author inoculated through the aorta, peripheral veins, the femoral 
 
158 IXFECTIOUS DISEASES. 
 
 or the carotid arteries, died at the end of a period varying from 
 thirty-six to forty-eight hours. 
 
 The results are altogether different when the anthrax passes 
 through the liver. Of twelve animals which received considerable 
 amounts of anthrax culture by the portal vein, only three died. The 
 liver, therefore, possesses the power to arrest the anthrax bacilli and 
 destroy them. This organ plays an important part in the protection 
 of the organism against anthrax infection. A dose of £ of a c.cm., 
 injected by a peripheral vein, killed a rabbit of 2345 grams in 
 thirty hours, while a dose of 8 c.mm., introduced bj^ a portal vessel, 
 was not sufficient to kill a smaller rabbit, weighing 1915 grams. 
 This demonstrates that an amount of anthrax bacilli sixty-four 
 times greater than that which kills through the peripheral veins 
 is completely annihilated by the liver. 
 
 The protective action of the liver was as well evidenced in experi- 
 ments with the staphylococcus aureus. 
 
 The sample employed, which was highly virulent, was diluted 
 with bouillon and injected, as was the anthrax, by five different 
 vessels. Contrary to the preceding results, the animals inoculated 
 by the distal end of the carotid artery succumb first. The brain, 
 therefore, represents an excellent culture medium for the staphylo- 
 coccus. In the second place, the animals injected by the aorta or 
 the femoral artery died. Those which received the virus by periph- 
 eral veins survived longer, and, finally, those which received it by 
 the portal vein resisted the inoculation. 
 
 "When we come to the streptococcus, we find that the liver exerts 
 no protective action. This microbe finds in the parenchyma of the 
 liver excellent conditions for vegetation, and the animals injected 
 by the portal vein are generally the first to succumb. Those which 
 have been inoculated by the aorta, the carotid, or the femoral artery 
 die shortly after. As to the animals which have received the virus 
 by the peripheral veins, they die tardily, or, if the virus is not too 
 active, they may survive. 
 
 Of the author's twenty rabbits inoculated by the various vessels, 
 all succumbed, while out of eight animals injected by the peripheral 
 veins, three survived. 
 
 The lungs, therefore, represent a protective organ against the 
 streptococcus. They play a role similar to that which the liver 
 fulfils with regard to the bacillus anthracis or the staphylococcus 
 aureus. There is this to be noted, however, that the destruction of 
 
DEFENSES AND REACTIONS OF THE ORGANISM. 159 
 
 pathogenic agents by I lie lunge Li less active. Tint organ doe* nol 
 neutralize more I nan one fatal d< ! 
 
 Willi the colon bacillus, the results seem somewhal Btrange. The 
 animals inoculated by the portal vein or the carotid artery are the 
 first to succumb. Those which receive the vim- by the aorta r< 
 quite frequently. It must be admitted, therefore, thai one of the 
 organs tributary to the arterial system destroys the microbes. 1' is 
 a curious fact that the liver, far from destroying this microbe, offers 
 it an excellent medium of culture. This resull explains well the 
 frequency and gravity of hepatic infections of gastrointestinal origin. 
 
 In order to impart a more general character to his researches, the 
 author undertook some experiments with culturesof oidium albican, . 
 The animals injected by the carotid artery axe usually the firsl to 
 die. The lungs very slightly retard the course of the infection. The 
 liver and the kidneys arrest great quantities of the parasites and 
 prevent extension of the process. These organs very efficiently j »r< i- 
 tect the economy. 
 
 The following table presents a resume of the results of the autl 
 researches on the protective role of the organs. It indicates the 
 effects of virulent inoculations and their variations according to the 
 vessels by which the cultures are injected: 
 
 ., • Staphylococcus. Streptococcus. Colon bacillus. 
 
 r Aorta Carotid artery Portal vein Portal vein 
 t very rapid -I Femoral 
 
 (. artery Carotid artery Portal vein Carotid artery 
 
 J more or less f Peripheral f Aorta Aorta 
 
 Death I rapid, but | veins Carotid artery 
 
 constant ] Carotid 1 Femoral Femoral artery 
 
 [ artery [ artery 
 
 .inconstant " " Periph'l veins " Peripheral veins 
 
 ■ frequent " " " " Periph'l veins Aorta 
 
 Survival < almost < „ , . . „ , , .. ., ,. 
 
 I constant {Portal vein Portal vein 
 
 Colon bacillus Bacillus of Oidium 
 
 of dysentery. dysenteriform enteritis. albicans. 
 
 Old cultures Fresh cultures 
 
 I very rapid Portal vein Portal vein Periph'l veins Carotid artery 
 
 j more or less i Peripheral Portal vein " " Aorta. 
 
 Death J rapid but -j veins 
 
 constant ( " Periph'l veins Periph'l veins Aorta 
 
 [inconstant " " " " " Peripheral veins 
 
 .frequent " " " Portal vein Portal vein 
 
 Survival -, almost Portal vein " " " Renal arterv 
 
 Ve 
 
 oust ant 
 
 Modifications of the Action of the Liver upon Microbes. The 
 protective action exercised by the liver toward infections seemed to 
 
160 INFECTIOUS DISEASES. 
 
 the author deserving of complementary researches. It was of interest 
 to learn what occurred under various experimental conditions. He 
 was led to study the influence of fasting, of microbic associations, 
 and of certain substances, such as glucose, sodium bicarbonate, and 
 ether. Excepting one series in which an anthrax culture was em- 
 ployed, staphylococcus aureus was always used. 
 
 influence of Fasting. Under the influence of fasting the protective 
 action of the liver diminishes, but quite slowly. After twenty-four 
 hours of starvation it is exerted to a normal degree upon the anthrax 
 bacillus. If the inoculations are made at the end of two or three 
 days the antibacterial power is found to be weakened, but not com- 
 pletely suspended. Injection by the portal vein is still less rapidly 
 fatal than that by some peripheral veins. This was demonstrated 
 by the results obtained with the staphylococcus aureus. 
 
 Microbic Associations. We have already pointed out that the effects 
 of microbic associations are due to the action of soluble substances. 
 Thus it is that sterilized cultures of the bacillus prodigiosus favor, 
 in a very marked degree, the pathogenic action of the staphylococcus. 
 Their injection by a branch of the portal vein diminishes the pro- 
 tective action of the liver and, if the dose be sufficient, may even 
 completely abolish it. 
 
 The fact that, under the influence of certain toxins, the protective 
 role of the liver is abolished, may possibly explain, in part, the 
 mechanism of microbic associations, which is as yet so little under- 
 stood. 
 
 The Influence of Glucose. Solutions of glucose were used in two 
 different ways. In some cases they were mixed with the culture and 
 injected into a branch of the portal vein. In other instances they 
 were administered by the stomach. In the latter case, its use was 
 continued for two or three days in succession. 
 
 The results were complex. One important fact is that the influ- 
 ence of glucose differs markedly with the quantity introduced. When 
 the sugar is directly injected into the blood by the portal vein, 3 to 
 5 grams suffice to diminish or suspend the hepatic action. When 
 it is introduced by the stomach, larger quantities are required. 
 Sixteen grams exert a decidedly harmful effect, but not as great 
 as that produced by the portal injection of 3 grams. Smaller 
 closes, on the contrary, exert a stimulating action upon the liver. 
 Thus, in one of the experiments, an animal which had received 1 
 c.cm. of a very virulent culture through the vein, and which ingested 
 
DEFENSES AND REACTIONS OF THE ORQANU v Hi] 
 
 5 grams of glucose on each of two succe ive da; . urvived even 
 days, while the control died in eighteen hour . 
 
 The Influence of Bicarbonate of Soda. The author'e expel iment - 
 
 with sodium bicarbonate are ao1 very numerous. The animals 
 which received 5 grams by Hie portal vein or io grama per OS 
 rapidly succumbed to Hie injection of relatively Bmall dosee of staph- 
 ylococcus by a mesenteric vein. Ii is probable thai the amounl "t 
 
 sodium bicarbonate injected whs loo great and, perhaps, by dimin- 
 ishing the dost 1 , different resulls would lie obtained. 
 
 The Influence of Ether. The action of ether likewise varies wilh the 
 
 dosage. The author, therefore, multiplied the experiments. Thirty- 
 four rabbits served for these series of researches. Some i if these were 
 
 used as controls; the others were treated in four different ways: Pure 
 ether or a solution of tin" same was injected by the portal veins, or 
 the animals were made to swallow one of these fluids. The solution 
 of ether was prepared by agitating ether with a 20 per cent . solution 
 of alcohol in water. The main fact resulting from these ex] leriments 
 is that five or six drops of pure ether introduced by an intestinal 
 vein completely abolishes the action of the liver. It is probable 
 that a part of the fluid diffuses and diminishes the general resist- 
 ance, since in several cases the animals died more rapidly than 
 those which had received the same dose by a peripheral vein. 
 
 When the method of ingestion is resorted to, it is found that doses 
 of 1.5 c.cm. of ether diminish but slightly the action of the liver. 
 In a dose of 1 c.cm. it seems to augment it. Smaller doses are best 
 given diluted. "When a dilution is directly injected into a vein it 
 diminishes or abolishes the action of the liver in a dose of 1 or 1.6 
 c.cm. By ingestion, greater amounts can be administered: 2 to 
 3 c.cm. of the solution represent an excellent therapeutic dose for a 
 rabbit of 2 kilograms. If the control dies rapidly, death of the 
 animal treated with ether is delayed: if the control dies only after 
 five or six days, the animal treated generally survives. 
 
 In brief, we conclude from these researches that the ingestion of 
 small doses of ether increases the antimicrobic action of the liver. 
 
 All these experiments were made with the staphylococcus. The 
 results obtained with the B. anthracis are analogous, although our 
 experiments with the latter microbe are not numerous. It is well, 
 however, to recall them, as they confirm the data already obtained 
 with regard to the slight action of transitory fasting and the harmful 
 influence of large doses of ether. 
 
 11 
 
162 INFECTIOUS DISEASES. 
 
 Defense of the Organism against Microbic Poisons. 
 
 Although the bacteria which vegetate upon the skin or in the 
 respiratory passages are incapable of secreting noxious substances, 
 this is not the case with those swarming in the digestive tube. It 
 is often asserted upon the dictum of CI. Bernard that the gastro- 
 intestinal cavity is outside the organism. In fact, it is true that, 
 in order to produce their effects, noxious substances must pass the 
 barrier opposed to them by the intestinal epithelium. It must, how- 
 ever, be remembered that all conditions seem to combine to favor 
 fermentations in the alimentary canal : fermentable materials, abun- 
 dant fluids, and favorable temperature. Therefore, toxins analogous 
 to those found in putrefactions are formed, as may be demonstrated 
 by a study of the contents of the intestine or of the fecal matters. 
 In infectious diseases, digestive fermentations are often intensified. 
 There is an addition of poisons formed under the influence of patho- 
 genic agents. Although the organism is constantly in danger of 
 intoxication, the realization is in most cases prevented by the agency 
 of various protective systems with which living beings are endowed. 
 
 Let us first consider the substances produced in the alimentary 
 canal. Stich asserted that they are not absorbed. This greatly 
 exaggerated view contains a certain amount of truth. The interest- 
 ing researches of Queirolo, Denys, Abelous, Charrin, and Cassin 
 establish the protective role of the intestinal epithelium. Its cells 
 act equally upon vegetable alkaloids and certain microbic toxins, 
 notably those produced by the colon bacillus. Poisons which escape 
 this first barrier penetrate, in small amount, by the lymphatic ves- 
 sels. They are then arrested and modified by the glands. The 
 greater part, however, passes into the blood — i. e., the portal vein — 
 and is thus carried to the liver. 
 
 Action of the Liver upon Microbic Poisons. The action of the 
 liver, so often studied and so well elucidated in cases of intoxications, 
 seems far less clear with regard to microbic poisons. It is necessary, 
 however, to distinguish the primary poisons from their derivatives. 
 The action of the fiver seems to be manifest upon the latter. The 
 author recognized this fact as early as 1887, when studying the 
 putrid poisons. The results of these experiments, reducing to kilo- 
 gram of animal the quantities of extract of tissues injected, are 
 summed up in the following table: 
 
DEFENSES AND REACTIONS OF THE ORGANISM. 103 
 
 Quantity introduced. 
 Do 
 
 Fluid injected. Inimal experimented. Non-fatal Fatal 
 Dialized extrad . . . J Healthy frog 300 
 
 i l rofl -.mi I, ..in b lii er, . . 300 
 
 Ethered extrad - , , [H< alth; 837 
 
 I Frog without a liver 837 
 
 I Rabbil 'i" i iph< ral vein). . . 91 
 
 Alcoholic ex1 racl . ■ " [portal vein) , . . . I < l 
 
 ' " (portal vein) 216 
 
 It will suffice to remark thai in the experiments upon the rabbil 
 the relation of fatal doses, according as the injection ia given by .•> 
 peripheral vein or some branch of the portal vein, is ae 2.36 to I. 
 It is, therefore, permissible to conclude thai the liver arreste <■< rtain 
 toxins extracted from putrid substances in the same manner 
 arrests vegetable alkaloids. It. can also acl upon various bodies 
 which often originate under the influence of microbes. Thus,accord- 
 ing to Kochs, it shares with the kidneys the property of presiding 
 over the modification of aromatic substances, and il ia known thai 
 aromatic substances, notably phenol, thus lose much of their noxious 
 power. 
 
 Microbes also give rise to the formation of ammonia, and the liver 
 again comes to the assistance of the organism by arresting and neu- 
 tralizing the ammonium salts, those at least in which the base is 
 united with carbonic acid or some organic acid. 
 
 The study of putrid substances is particularly interesting because 
 of the deductions that may be drawn for the history of intestinal 
 fermentations. The substances originating in the digestive tube are, 
 in fact, analogous to putrid substances, and the liver also acts upon 
 these poisons. 
 
 The researches of Drs. Teissier and Guinard 1 have led to the unex- 
 pected conclusion that the liver exerts no protective action against 
 the toxins of diphtheria and of pneumobacillus. Xot infrequently, 
 especially in the dog, the action of the poison is more energetic when 
 it passes through the liver. 
 
 These results should not, however, be hastily generalized. The 
 toxin of the dysenteric colon bacillus is neutralized by the liver. 
 AYhile 0.5 com. injected into the peripheral veins of a rabbit kills 
 this animal in two or three days, an amount four times greater intro- 
 duced by the portal vein causes simply diarrhea. If greater quan- 
 
 1 Teissier et Guinard. Rccherehes experimentales sux les effets des Toxines micrc- 
 biennes et sur quelques influences capables de les modifier. Arch, de med. exper.. l v "7. 
 p. 994. 
 
1(34 INFECTIOUS DISEASES. 
 
 tities are administered, the liver is no longer capable of saving the 
 animal, but prolongs its existence. Twenty cubic centimetres of a 
 slightly weakened culture were injected into two rabbits. One, 
 weighing 1S25 grams, received the fluid by a peripheral vein, and 
 died in collapse at the end of seven hours and a half; the other 
 animal, weighing 1S15 grams, received the poison by the portal 
 vein, and died at the end of four days. 
 
 Action of the Various Organs upon Microbic Poisons. Recent 
 researches establish that the lungs are able to attenuate the action 
 of certain poisons. They act upon vegetable alkaloids and sub- 
 stances such as ammonium carbonate and fatty acids, which may be 
 produced under the influence of certain microbes. However, its 
 influence upon toxins, at least upon the diphtheritic toxin, seems to 
 be nil. Animals comparatively inoculated by the carotid artery and 
 the jugular vein die within the same period of time. The artificial 
 circulation of the toxin through the lungs, even when prolonged for 
 nearly an hour, in nowise modifies its action. No general conclusion 
 should be drawn from this negative result, which must lead only to 
 further investigations. It should be equally interesting to study 
 the action which other parts of the organism — the spleen, the thyroid 
 gland, the suprarenal capsules, the bone-marrow, the thymus, etc. 
 — may exercise upon toxins. All that we know, since the remark- 
 able experiment of Wassermann and Takaki, is that the brain pos- 
 sesses the power to fix and aniiihilate the toxin of tetanus. 
 
 Modes of Elimination of Toxins. As soon as microbic toxins enter 
 the blood they probably undergo attenuation by oxidation or by 
 neutralization exercised through certain principles which the leuco- 
 cytes diffuse. As already stated, the kidneys also serve for the 
 elimination of toxins. It may, however, be a question whether 
 they simply excrete the circulating poisons or whether they pre- 
 viously submit them to some analysis. As a matter of fact, it has 
 been demonstrated that infectious poisons contained in the organism 
 are albuminoid substances. Those contained in the urine are of an 
 alkaloid nature and, unlike the former, resist higher temperatures 
 fairly well. It may, therefore, be asked whether the primary com- 
 plex molecule is not broken up in the kidneys and does not leave 
 in these organs its alkaloidal radical. This is no more than an 
 hypothesis, but is worthy of verification. The remark might even be 
 extended to autointoxications. In the course of uremia, the poisons 
 contained in the blood and organs are likewise of an albuminoid 
 
DEFENSES AND REACTIONS OF THE ORGANISM. ]<;:> 
 
 nature, while the urinary poison is not an albumin. El may, tl 
 fore, be supposed that the kidneys possess the power of breaking 
 the complex molecules of the products of di at imilation. In this 
 manner, better perhaps than by an internal ecretion, may be 
 explained those cases of uremia which occur when the permeability 
 of the kidneys is but slightly modified. 
 
 There are other modes of depuration. The respiratory apparatus 
 eliminates volatile substances, probably the leasl importanl ones, 
 some of them chemically defined. They imparl to the breath the 
 disagreeable odor observed in various infections, notably in those 
 attended by increased intestinal putrefactions. The skin, likewise, 
 may eliminate toxins, and, like the lungs, throws ou1 volatile sub- 
 stances, among which sulphuretted hydrogen, ammonia, fatty acids, 
 and acetone occupy the first rank. It may also eliminate a certain 
 amount of noxious substances with the perspiration. We are not, 
 however, well informed upon this point, and accurate experiments 
 are lacking. It is well to remember that subcutaneous injections 
 of pilocarpine often produce an improvement in the general state 
 of patients suffering from diphtheria. It would be interesting to 
 inquire into the properties of the increased perspiration secreted under 
 these conditions. The eliminating role of the bile and gastrointes- 
 tinal secretion is not any more clearly understood. The frequency 
 of diarrhea and vomiting in animals which have received microbic 
 toxins tends to demonstrate the existence of elimination through the 
 alimentary canal. This hypothesis, to which occurrences in certain 
 cases of poisonings also point, finds an additional support in the 
 researches pursued by the author upon the toxins of the colon bacillus 
 of dysentery. When the toxin was prepared with a sample of mod- 
 erate virulence and was relatively weak, its introduction caused pro- 
 fuse diarrhea. When it was derived from a highly virulent sample, 
 its action was more powerful, but there was very little, if any, 
 intestinal flux. 
 
 Our knowledge concerning the passage of toxins into the milk is 
 far from complete. A few observations, notably those reported by 
 Sevestre, Lesage. and Siebert, tend to prove that the use of tainted 
 foods may cause diarrhea in the mother and the nursling. In a case 
 mentioned by Lesage the child, seven months old, died in forty-eight 
 hours with symptoms of infantile cholera. Facts have been pub- 
 lished demonstrating that even a benign intercurrent infection may 
 impart to the milk a certain degree of toxicity and give rise to various 
 
166 IXFECTIO US DISEASES. 
 
 manifestations and particularly to diarrhea in the child. This has 
 been observed in a case of phlegmonous tonsillitis (Henoch) and of 
 vaccinia (Marfan). The experiments of Brieger and Ehrlich demon- 
 strated that the toxins of diphtheria, tetanus, and typhoid fever pass 
 into the milk. According to Pasquale and Michele, the same is true 
 of those of tuberculosis. It must be remarked, however, that though 
 the milk of sick women is at times contaminated, it may, in the 
 majority of cases, be ingested without any inconvenience. In the 
 writer's hospital wards he allows the mothers to nurse their infants 
 when the infection from which they suffer is to be of short duration. 
 A great number of women suffering from measles, scarlatina, mumps, 
 erysipelas, sore throat, or even diphtheria, have continued to nurse 
 without any harmful results for the nurslings. It has been necessary, 
 in most cases, only to supplement the diminished secretion of the 
 mother's milk by artificial feeding. As soon, however, as deferves- 
 cence took place, the secretion was re-established. The author was 
 inspired to this practice by the desire to avoid weaning the children 
 definitely, since the effects of artificial feeding, especially among the 
 poor classes, are only too well known. 
 
 The Reactions of the Organism against Infections. 
 
 Role and Signification of Local Lesions. Disease is the result of 
 two contrary actions : In the first place, there is an attack of some 
 pathogenic agent upon the organism. In the second place, a series 
 of reactions calculated to hinder or neutralize the morbid effects 
 occur. 
 
 To take a very simple example, let us suppose a pyogenic coccus 
 to have been deposited beneath the skin. This microbe, finding in 
 the interstitial fluids of the tissue conditions favorable for its devel- 
 opment, rapidly multiplies. If it behaved like a simple inert body, 
 it might form large colonies without producing any appreciable 
 reaction on the part of the organism. Not so, however. The microbe 
 elaborates soluble substances, some of which alter the surrounding 
 tissues, and others, carried by the circulation, directly influence the 
 entire organism. Reactions on the part of the organism are then 
 aroused. If the substances elaborated by the microbe are very 
 active they cause immediate death of the cells with which they come 
 in contact. If less energetic, they give rise to an irritation which 
 is expressed by responsive phenomena occurring in the cell and 
 
DEFENSES AND REACTIONS OF THE ORGANISM. [67 
 
 without any intervention of the nervous system or the circulation. 
 At the same time, the microbic substances and the products elabo- 
 rated by the altered cells excite the surrounding vessel and especially 
 the nerve terminations. By this mechanism a series of new morbid 
 manifestations is produced, some of which, of a true reflex nature, 
 return to the starting poiul of excital ion, while other extend to the 
 most distant parts of I lie organism, 
 
 Even when the lesion remains local and the toxins do not pene- 
 trate (lie economy Hie nervous system which, under normal condi- 
 tions, assures functional synergy, suffices, under pathological condi- 
 tions, to give rise to a series of morbid sympathies. However, toxins 
 are almost always absorbed and, at points at which they reach the 
 cells, they induce manifestations identical with those which occur 
 at the point primarily invaded, viz., irritation of the cells, cellular 
 reactions, excitation of bloodvessels and nerve terminations, reflex 
 to the point of origin and reflex to distant parts. Finally, in a great 
 number of instances, the figurate elements also penetrate the econ- 
 omy, settle at certain points, elaborate toxins, and the series 
 manifestations just described immediately recur. 
 
 If we consider the point primarily attacked by a microbe which has 
 been deposited beneath the skin, for example, we see that at the 
 point of its introduction a series of manifestations develop, resulting 
 in the production of a local lesion. The latter represents a true 
 barrier opposed to the invasion of the pathogenic agent. It is 
 absent under two quite different circumstances. If the microbes 
 meet an organism endowed with perfect immunity, the interstitial 
 fluids exert a germicidal action upon them and prevent their devel- 
 opment. A certain number of them are killed and the action of the 
 others is inhibited to such a degree as to allow the leucocytes to 
 completely eliminate them from the economy. In this instance the 
 local lesion is not produced, because it would be of no use. The 
 organism is so resistant that the invader is destroyed without any 
 apparent struggle. Even in such cases, however, the destruction of 
 bacteria is not as speedy as might appear at first sight. Certain 
 non-pathogenic bacteria, especially if they are sporulated, may sur- 
 vive for a very long period of time. They remain as harmless foreign 
 bodies, and behave altogether like insoluble substances. It is likely 
 that they give rise to no defensive reaction because they are devoid 
 of irritant secretions. 
 
 When the microbe is highly pathogenic or the organism non- 
 
168 INFECTIOUS DISEASES. 
 
 resistant the local lesion is likewise wanting, although for quite 
 different reasons. The fluids then exercise no germicidal power, the 
 microbe rapidly develops and, at the same time, secretes toxins, some 
 of which, being absorbed, paralyze the nerve centres and prevent 
 vasodilatation preparatory to serious exudation and diapedesis. 
 Others exercise a negative chemotactic action, viz., repel the few 
 phagocytes which approach the infected focus. 
 
 In cases in which the invading microbe is virulent the local lesion 
 represents a salutary reaction. This reaction, however, like all other 
 reactions, may become a new source of danger. A microbe which 
 is implanted in a mucous membrane is capable of causing very 
 serious accidents : for example, in the larynx, edema of the glottis ; 
 in the lungs, foci of fibrinous pneumonia and bronchopneumonia, 
 which, by their extent, may prove fatal. 
 
 On the other hand, the effect may exceed the end. The organism 
 at times mobilizes all its reserves upon slight alarm, and thus creates 
 useless lesions. The congestion which surrounds a circumscribed 
 pulmonary lesion must often be combated. The same is true with 
 regard to diarrhea and effusions in serous membranes which some- 
 times reach considerable amounts in disproportion to the slight 
 morbid cause that gives rise to all these effects. An interesting 
 experiment of Gamaleia shows how excessive and dangerous organic 
 reactions may sometimes become. This author produced in two 
 rabbits a chemical irritation of the cornea. In one, reaction was 
 allowed to follow its natural course, and terminated in an opacity. 
 In the other case, the reaction was checked by various procedures 
 which prevented the reflex congestion of the neighboring parts, and 
 the cornea remained transparent. 
 
 The practical importance of these pathogenic data is readily con- 
 ceived. Since therapeutics furnishes us with means capable of 
 intensifying or attenuating reactionary phenomena, it is the duty 
 of the clinician to determine the conditions under which the inflam- 
 matory reaction is produced, to recognize whether it is useful, insuf- 
 ficient, or excessive, and to respect, intensify, or moderate it accord- 
 ingly. 
 
 Inflammatory Reactions. Whether or not a local lesion exists, 
 microbes may invade the economy and settle in tissues and organs. 
 In other cases they remain localized at the point of introduction, 
 but secrete substances which diffuse and impregnate the economy. 
 In both instances, visceral foci develop which, in their turn, become 
 
DEFENSES AND REACTIONS OF THE OBQ i VI8M. 169 
 
 the starting point of morbid reactions. The e reactionary phenom- 
 ena are known under the name of inflammation, 
 
 No term is oftener employed in medicine, and none, perhaps, hag 
 a meaning as much lacking in precision at the word inflammation. 
 
 Discarding the ancient theories, which are merely of historical 
 interest, we find, a1 the presenl epoch, al leasl three differenl con- 
 ceptions of the process in quesl ion : I . Thai of Virchow, according i<> 
 which inflammation is characterized essentially by cellular alterations, 
 the vascular phenomena being of secondary importance. 2. Thai 
 of Cohnheim, who sees in inflammation the sum of proa which 
 begin by vascular dilatation and resull in transudation and diape- 
 dosis (migration). 8. Thai of Mctchnikoff, who defines inflammation 
 as ;i salutary reaction tending to check infection by phagocytosis. 
 
 Whosoever, independently of theoretical discissions, looks for a 
 characteristic of inllannna.tion will see that this term must retain a 
 very comprehensive meaning. As the question here concern- infec- 
 tious diseases, we shall define inflammation as "the ensemble of 
 reactionary phenomena produced at the points irritated by microbic 
 toxins." 
 
 These phenomena are multitudinous and may be classified as 
 follows: 
 
 Alteration of fixed cells. 
 Reflex vascular disturbances. 
 Exudation and diapedesis. 
 
 Though not the first by order of occurrence, vascular disorders are 
 first observed. They are easily appreciable, and the patient himself 
 may notice them by the intensity of painful pulsations which he 
 experiences. The clinician as well as the anatomist detects them 
 without difficulty. It has, therefore, been asserted that congestion 
 is the first stage of inflammation. As a matter of fact, it is preceded 
 by a local change in nutrition. It is readily understood that, in 
 reality, the presence of microbic poison modifies the medium which 
 surrounds the cells, and, as life is an adaptation of the cells to the 
 medium, when the latter changes the cells also must be modified. 
 Their nutrition and. consequently, their activity cannot remain what 
 they previously had been. There will first occur a dynamic change 
 in the cell, which change will bring in its train further histochemical 
 modifications. A lesion appreciable under the microscope may soon 
 be detected, but it certainly is not the primary lesion. It is the 
 result of a previous disturbance in cell function. 
 
170 INFECTIOUS DISEASES. 
 
 The excitation of nerve terminations by microbic toxins and by 
 the products secreted by the already modified cells produces an 
 active reflex vasodilatation at the point attacked. It is readily con- 
 ceived that the more excitable the nervous system the earlier will 
 congestion set in and, consequently, the more acute the process will 
 be; that is to say, the greater will be the chances of a favorable 
 evolution. A very simple experiment confirms this hypothesis. 
 After the sensory nerves of a rabbit have been sectioned at the base 
 of the ear, it is noticed that the subcutaneous inoculation of the 
 streptococcus produces far graver lesions than in the intact ear. 
 
 According to the qualities of the pathogenic agent and the respon- 
 sive aptitude of the organism, congestion may be effected in a slow 
 and progressive manner or rapidly, almost suddenly. In the latter 
 case, if an important organ is invaded, disturbances may suddenly 
 become manifest. Everyone is acquainted with the violent pain 
 and dyspnea attending acute congestion of the lungs. 
 
 Preceding and explaining serous exudations and cliapedesis, acute 
 congestion represents the first stage of inflammatory reaction. It is 
 the beginning of a defensive act. Therefore, whenever reaction is 
 tardy or weak we must stimulate the process. Three procedures, 
 practised upon animals, enable us to obtain this result, and all three, 
 by stimulating inflammatory reactions, favor healing of the lesions. 
 First, section of the sympathetic, the influence of which upon the 
 course of experimental erysipelas has been shown (Roger). Secondly, 
 heat, by the agency of hot water circulating about the affected parts 
 (Filhene). Therapeutics demonstrates the same favorable influence 
 of hot applications in the treatment of erysipelas, and popular tradi- 
 tion has long taught us that a paronychia may be cured by plunging 
 the finger in almost boiling water. In this case the temperature is 
 not sufficiently raised to kill the microbe; the action is indirect 
 through the congestion thus produced. Finally, as Dr. Carnot has 
 pointed out, analogous results are obtained by submitting the inocu- 
 lated animals to the influence of vasodilating substances, such as 
 amyl nitrite. 
 
 Acute vasodilatation of the affected region is expressed by increased 
 afflux of arterial blood and, consequently, acceleration of the circu- 
 lation. The blood remains red in the veins. This result is impor- 
 tant, as the leucocytes cannot leave the vessels except when the 
 supply of oxygen is considerable. If the veins are compressed so as 
 to slow the blood current, migration no longer takes place. 
 
DEFENSES ANh REACTIONS OF THE OROA VJSM. 17] 
 
 The exodus of leucocytes is preceded by an intermediate 
 ■second stage of inflammation characterized by a lowing of the 
 blood current. Then there occur whal Cohnheim bag described as 
 "marginatum" of the leucocytes. These cells areseen to adhere to 
 the wnl Is of the veins, while in the capillaries they remain mixed with 
 the red corpuscles. 
 
 Then begins the third Btage, characterized by two events of prime 
 importance, migration and exudation. 
 
 The leucocytes puss ou1 of the smaller veins and capillaries. Those 
 passing out through the hitler route lenvc behind them small aper- 
 tures through which a few red corpuscles may also escape. Nol all 
 leucocytes, however, are of the migratory variety. The lymphocytes 
 are but slightly motile. The eosinophils are endowed with sluggish 
 motion. It is especially the varieties known as mononuclear and 
 polynuclear neUtrophiles that take the greatest part in the pr< 
 and are particularly charged with the task of incorporating and 
 digesting the microbes. 
 
 Coincidently with this migration there occurs a more or less abun- 
 dant exudation consisting of a serous or serofibrinous fluid. 
 
 It is difficult to gain an insight into the mechanism of exudation. 
 The mechanical explanation, at first accepted, is daily losing ground. 
 It is admitted that venous stasis cannot account for the process and 
 that ascites as well as hydrothorax and hydrocele must be attributed 
 to a subacute or chronic inflammation of the peritoneum, pleura, or 
 the tunica vaginalis, respectively. This view may be supported by the 
 well-known experiments of Ranvier and those pursued by the author 
 with Dr. Josue. 1 They have shown that ligature of the three efferent 
 veins of the pinna of the ear is not followed by an effusion into the 
 cellular tissue of the organ; but if at the same time the superior 
 cervical ganglion of the sympathetic is excised, or if a few dro] - 
 a sterilized culture of bacillus proteus is injected, edema appears 
 and persists for several days. 
 
 The inadequacy of the mechanical theory is further shown by the 
 fact that the transuded fluid does not possess the same constitution 
 as the blood plasma. The amount of salts is the same; but not so 
 when the organic materials are considered, which seem to be fur- 
 nished in a selective manner, as a true secretion. 
 
 When once out of the bloodvessels, the leucocytes proceed toward 
 the points occupied by the microbes, and attack them. There has 
 
 1 Roger et Josue. Xote sur la pathogenie de I'oedeme. Soc. de biologie. July 27 1 - 
 
172 INFECTIOUS DISEASES. 
 
 been much discussion in reference to the wonderful faculty with 
 which they are said to be endowed or the kind of instinct they 
 display. Recent researches demonstrate that the process is one 
 embraced by a law of general biology. It is a phenomenon first 
 studied by naturalists, and which PfeifTer has described under the 
 name chemotaxis, and of which Pekelharing and especially Bordet 
 and Massard have shown the importance in animal pathology. 
 
 The soluble substances maybe divided into three groups, according 
 as they attract, repel, or exert no action whatever upon the leuco- 
 cytes. 
 
 The majority of microbic products, and notably those of staphy- 
 lococcus aureus, attract the migratory cells. The waste products 
 of the cells of the economy do the same, a fact of the greatest con- 
 sequence, since, from the very beginning and during the entire course 
 of infection, microbes secrete substances which alter or kill the cells. 
 On the contrary, the bacillus of chicken cholera exercises a negative 
 chemotactic action, viz., it repels the leucocytes, at least those of 
 the rabbit. Hence, the facility of microbic generalization. 
 
 The round cells which are found in an inflammatory exudate are 
 not all derived from the blood. A certain number of them are fur- 
 nished b}^ the fixed cells of the connective tissue. In this connection 
 the most interesting modifications are those of the giant elements 
 described by Ranvier under the name clasmatocytes. 
 
 The fat of the adipose cells disappears and the elements resume a 
 younger form. The endothelia likewise tumefy and return to their 
 embryonal shape. In a word, the cells of mesodermic origin resume 
 the functions which they exercised during the embryonal period. 
 They recover their contractility and motility. This law seems to 
 be applicable even to the muscular fibres. In this instance, however,, 
 more highly organized and, consequently, more sensitive elements 
 are concerned. Therefore, the process of degeneration prevails over 
 the reactionary phenomena. 
 
 In the midst of these profound modifications the epithelial cells 
 do not remain intact. If the toxins are not very noxious the modi- 
 fication of the medium excites an increased activity on the part of 
 the cellular element, and the phenomena of proliferation and notably 
 karyokinetic figures occur. "When, on the contrary, the toxins are 
 highly energetic, the exchanges between the adulterated medium and 
 the epithelial cells cause a series of functional disturbances which 
 soon result in structural modifications. The cell may be killed at 
 
DEFENSES AND REACTIONS OF THE ORGANISM. 17-; 
 
 I he outest. H. undergoes a particular fermentation which tran forms 
 [t into a homogeneous mass resembling fibrin. This is known at 
 coagulation necrosis. In case theelemenl is still capable of reacting 
 it presents the scries of lesions which have been described a granular, 
 pigmentary, hyaline, colloid or mucous, vitreous, ca eous degenera- 
 tion, and the like. It may be stated that, as a rule, degeneration 
 occurs more frequently and earlier in epithelia than in connective 
 tissue cells, for I he re: i son thai the structure of the former is more deli- 
 cate and renders them more sensitive to various morbific influences. 
 
 The changes in the structure of cells revealed by the microscope 
 result, as already stated, from functional disorder caused by modi- 
 fications of the medium. II musi be noted, however, thai the nutri- 
 tional disturbances in their turn influence the function- of the cells 
 and notably their secretory activity. In cases of slight inflamma- 
 tion the cells react with energy, and their secretions are more abun- 
 dant than under normal conditions. It will suffice to recall the 
 intense salivation occurring in angina, the nasal flow in coryza, 
 bronchial hypersecretion in inflammations of the respiratory 
 sages, the diarrhea in enteritis, etc. When the process is violent, 
 the reverse is observed. Secretions dry up: the tongue, the throat, 
 the skin are dry, and urine is scanty 
 
 According to the nature or intensity of the process, the aspect of 
 the inflammatory focus varies considerably. In its simplest expres- 
 sion the lesion consists of a serous exudate. In a higher degree, the 
 fibrin coagulates, pseudomembranous deposits appear, and exudates 
 are formed. If the toxins cause the death of a certain number of 
 cells, the exudate undergoes a purulent transformation. In other 
 instances bacteria produce therein fermentations similar to those 
 characterizing putrefactions. The result is then a putrid effusion 
 or a gangrene, according as the process occurs in the exudated fluid 
 or in the tissue itself. 
 
 When the round cells are very abundant they are either scattered 
 or form nodules. These embryonal masses may undergo a seri' - 
 changes resulting in the production of simple or specific inflammatory 
 granulations, such as infectious nodules, tubercles, syphilomata. 
 lepromata, and the like. 
 
 As to reparation of the lesion, it may be complete or incomplete, 
 viz., the tissue may resume its primary aspect or permanently retain 
 lesions — indelible marks of the inflammatory process oi which it has 
 been the seat. 
 
1 74 JXFECTIO US DISEASES. 
 
 Iii the former case the lesions have been slight. A few cells 
 perished in the struggle, but were picked up and digested by the 
 macrophages'. The survivors which, during the stationary period, 
 were in kar.yokinesis, rapidly replaced the destroyed elements. 
 
 When, however, the process is intense or lasts for a long period 
 of time, complete repair is impossible. The epithelial elements 
 undergo too profound degeneration or perish in too great numbers. 
 They are then replaced by connective tissue which, owing to its 
 more elementary organization, is more resistant. A sclerotic tissue 
 is thus produced which is at first traversed by numerous vessels, 
 but the latter are not endowed with great vitality, and soon dis- 
 appear, leaving the cicatrix in a state of dried tissue. 
 
 Serous Exudates. Serous exudations may be produced in the 
 subcutaneous cellular tissue, in serous membranes, in parenchymas 
 like the lungs, and less often in glands, as is the case in mumps. 
 These exudates resemble the blood serum, but differ among them- 
 selves in their chemical composition. From this standpoint they 
 have been divided into two classes : One comprises the inflammatory 
 serosities, with a specific gravity reaching or exceeding 1018. These 
 are remarkable for their richness in proteid substances and in fibrin, 
 and coagulate spontaneously in the air. The second class com- 
 prises the mechanical dropsies, which contain but a small amount 
 of nitrogenous substances, and do not coagulate unless certain 
 elements, such as blood serum, ferment solution, or myosin are 
 added. 
 
 Between these two extreme types there are numerous transitions. 
 Belief in the importance of mechanical exudation is on the decline. 
 It is asserted that even in cases of cardiac and Bright's disease serous 
 exudations are often ascribable to the presence of bacteria. Undoubt- 
 edly all edemas should not be considered as inflammatory in nature. 
 Venous stasis, cardiac incompetency, renal impermeability, and ner- 
 vous derangements produce edemas independently of all inflamma- 
 tory process. These facts are relatively rare, however, and most of 
 the dropsies of serous membranes are held to be subacute inflam- 
 mations. This view finds strong support in the fact that a great 
 many microbes are capable of producing edema, as has experimen- 
 tally been demonstrated with the bacillus anthracis, the bacillus of 
 diphtheria, and the streptococcus of erysipelas. Nearly all the 
 known microbes might be cited as capable of giving rise to subcu- 
 taneous edemas. Among the most important may be mentioned 
 
DEFENSES AND REACTIONS OF THE ORGANISM. [75 
 
 the bacterium lymphagogon of Hamburger, the proteu< vulgaris, 
 whose soluble products have also an edemagenic influence, and the 
 staphylococcus aureus. The last-named microbe i- habitually con- 
 sidered as no more than a pus coccus. The author ha* noticed, 
 
 however, Mini Hie siihciii.-uieoii.-' i 1 h >ci iln 1 ion of certain samples pro- 
 duces considerable edemas proving rapidly fatal, withoul the forma- 
 tion of pus. This result is not surprising, as most, If nol all, of the 
 microbes above referred to are ap1 to produce either edema or sup- 
 puration. In Mie former case I he pathogenic agenl is very virulent ; 
 serous exudation takes place, 1 ml (lie leucocytes cannot enter the field 
 in sufficient numbers. In the latter case the microbe is less ac 
 and migration is produced. In spile of appearances, the two pro- 
 cesses are the same, differing only in degree. Anthrax, for instance, 
 gives rise to a fatal edema in the guinea-pig and rabbil . In the adult 
 rat, which is wellnigh refractory to the disease, an abscess is the 
 result. Samples of staphylococcus when attenuated by successive 
 cultures in artificial media become pyogenic. The same is true of 
 the streptococcus. According to the degree of virulence of the 
 sample or the resistance of the animal, the result is death without 
 a local lesion, development of a fatal or curable edema, or production 
 of a localized abscess of little gravity 
 
 Our knowledge concerning the chemical constitution of inflam- 
 matory subcutaneous edemas is very limited. All we know is that 
 they differ from blood serum and lymph. They also differ from one 
 case to another. They are not like the exudates of the serous mem- 
 branes. It may, therefore, be concluded that they are due not to 
 simple transudation, but to a sort of secretion, or at least, according 
 to Jaccoud's expression, to a selective transudation. 
 
 Pleural exudates have more particularly attracted the attention 
 of chemists, and the difference between inflammatory and simply 
 dropsical effusions is clearly established. The latter process is to be 
 understood as an inflammation of subacute or torpid character. 
 Halliburton, who analyzed three cases of pleurisy and three of 
 hydrothorax, gives the following demonstrative figures: specific 
 gravity varied from 1020 to 1023 in the former instance : from 1012 
 to 1016 in the latter. Proteid substances, in pleurisy, oscillated 
 between 34 and 52 per 1000. Fibrin amounted to 0.1 or 1 : globulin, 
 12 to 30; and serin, 11 to 33 per 1000. In hydrothorax. proteid 
 materials did not exceed 13 to 25: fibrin. 0.06 to 0.1: and serin. 7 
 to IS. Globulin varied from 4 to 7 per 1000. These results clearly 
 
1 76 IXFECTIO US DISEASES. 
 
 show that inflammatory exudates are denser, richer in protein, and 
 especially in fibrin. It is but just to recall that Mehu's researches 
 already pointed to these conclusions. 
 
 Pseudomembranes. It is customary in Germany to divide pseu- 
 domembranous processes into two groups, namely, superficial or 
 croupous, and diphtheritic or profound. These expressions lead to 
 confusion, and must be abandoned. They correspond, however, to 
 a necessary distinction. As a matter of fact, in some cases the false 
 membrane covers up a mucous membrane, of which it reaches the 
 most superficial parts only. In other instances, the pseudomem- 
 branous exudate results from a necrosis of a more or less profound 
 diphtheroid gangrene. The former process is realized by certain 
 microbes, notably the bacillus of diphtheria. The latter process 
 characterizes the destructive affections of toxic or microbic origin. 
 Caustics, such as silver nitrate, and the most varied microbes may 
 produce lesions of membranous character. Such is the case in ulcer- 
 ating stomatitis, which actually represents a superficial gangrene of 
 the mouth. Such is also the case in certain pseudomembranous 
 cystites, pyelites, and ententes. The so-called false membranes are 
 nothing more than parts or shreds of the altered mucous membrane. 
 
 There is, then, a marked difference between the two processes. 
 The first is due to a general reaction of the organism; the second 
 results from the necrosing action of a pathogenic agent. The former 
 is characterized by the development of a concrete exudate upon the 
 surface of a mucous membrane ; the latter by exfoliation and expul- 
 sion of a pre-existing part which has been killed. 
 
 Leaving aside the description of diphtheroid gangrenes, which will 
 be discussed elsewdiere, let us now consider the true pseudomem- 
 branous process. 
 
 Under the habitual conditions of life this process may be considered 
 as always dependent upon microbic infection. There is not, how- 
 ever, a specific diphtherogenic microbe. The false membrane repre- 
 sents a quite common reaction which may be excited by a number 
 of bacteria. On the other hand, an agent capable of giving rise to 
 the formation of a false membrane may in other instances produce 
 an edematous exudation or a purulent focus. The difference depends 
 upon the virulence of the microbe, the seat of the lesion, and the 
 condition of the subject. These secondary influences intervene in 
 all cases, even when Loeffler's bacillus is the agent concerned. The 
 diphtherogenic action of this microbe is manifested only in parts in 
 
DEFENSES AND IlEAOTIONS OF THE ORGANISM. 177 
 
 contact with air, while subcutaneous inoculations produce only 
 edema rich in fibrin, but no false membrane 
 
 It is :i well-established law thai the figurate agents ad only by 
 their secretions. This law is applicable to the pseudomembranouf 
 processes. It has for a long time been believed thai false membranes 
 were not produced except under the influence of living bacteria 
 acting upon an altered mucous membrane, and thai theeffed of the 
 toxins was simply to induce a vasodilatation permitting the migra- 
 tion of leucocytes. 
 
 This conception has been abandoned in consequence of experi- 
 ments pursued by Dr. Bayeux and the author and the confirmative 
 researches of Dr. Morax. From these investigations it was shown 
 that the diphtheritic toxin introduced into the trachea may be 
 absorbed by the respiratory passage and give rise to a general in 
 cation. This is what occurs in animals highly sensitive to this poison , 
 such as the guinea-pig. In rabbits, which are more resistant, a local 
 reaction is often produced, resulting in the formation of a false mem- 
 brane. It seems that, in this instance, the poison exhausts itself in 
 local effects, since if the animal is sacrificed nothing but mechanical 
 lesions, such as pulmonary emphysema, are found. Visceral lesions, 
 which express general intoxication, are absent. We may, therefore, 
 extend to toxins what is already demonstrated with reference to 
 living microbes — viz., that the local lesion is the sign of attenuated 
 poison. At all events, it is produced only when the animal is endowed 
 with a certain degree of resistance. 
 
 Similar results may be obtained by operating upon other mucous 
 membranes. It has been possible to produce pseudomembranous 
 conjunctivitis, vulvitis, etc., by simply depositing the pure toxin of 
 diphtheria upon the mucous membrane; but, as this has already been 
 demonstrated with regard to suppuration, the more slowly the poison 
 penetrates the greater is the success of the experiment. 
 
 Experimental results explain certain clinical facts in which false 
 membranes were found to have extended far beyond the seat of 
 microbic colonies. Such was the singular case which the author 
 observed with Dr. Gamier. 1 A false membrane originated at the 
 level of the superior vocal cords and epiglottis and extended unin- 
 terruptedly as far as the smallest bronchial ramifications. .Is may 
 be seen in the figure below, the false membrane represents a perfect 
 
 1 Roger et Gamier. Diphterie traeheo-bronchique generalise. Presse ni£d., Nov. 9, 
 1898. 
 
 12 
 
178 
 
 IXFECTIO US DISEASES. 
 
 mould of the bronchial tree. Below the ramifications of the third 
 order the membrane was so thin that it was impossible to extract 
 more than fragments. It is readily conceivable that tracheotomy 
 failed to relieve the patient, since the obstruction of the respiratory 
 
 passages was complete. 
 
 Fig. 1. 
 
 Diphtheritic false membrane. 
 
 The nature of the production was verified by cultures. At the 
 time of admission of the sufferer a culture was made with exudates 
 taken from the tonsils, and the presence of LoefHer's bacillus was 
 demonstrated. At the necropsy fragments were taken from the 
 middle intrapulmonary ramifications and cultivated. A small num- 
 ber of the bacilli were found. The culture tubes inoculated with the 
 material from the last ramifications remained sterile. 
 
 The extension of the process cannot, therefore, be attributed to 
 
DEFENSES AND REACTIONS OF THE ORGANISM. 17!' 
 
 the propagation of the bacilli, since their number dimini bed in pro 
 portion to the distance the points examined were from the lar 
 and disappeared in the smallesl branches of the bronchial tube. 
 
 To explain the production of pseudomembrane . several the< 
 have been advanced. The simplesl idea is to assume an exudation 
 of a fibrinogenic substance which coagulates on contacl with the air. 
 Wagner asserts thai false membranes are produced by the celh of 
 the tissues which unite by means of prolongations. Ii Ls qow gen- 
 erally admitted that an exudate is constituted, on the one hand, of 
 fibrinogenic substance and, on the other, of altered cells. The fibrino- 
 genic substance escapes from the vessels and finds the besl condi- 
 tions for coagulating— it is in contacl with the air, it meete with 
 dead leucocytes which here, as everywhere, play a greal pari in 
 coagulation; it is spread out upon a mucous membrane the cells of 
 which are diseased. From the time of Cohnheim and Weigerl it has 
 been known that epithelia as well as endothelia do not oppose the 
 coagulating of exudations except when they are intact. At the same 
 time a certain role is to be attributed to the cells of tissues which 
 become fibrinified according to the process described by Weigerl 
 under the name coagulation necrosis. 
 
 Thus, made up at the expense of the fibrin of the blood and of 
 the cells, false membranes appear under variable aspects. They may 
 be found in serous exudates where they float in the fluid. In other 
 cases they are more abundant and line the two surfaces of the serous 
 membrane, and may cause them to adhere. Lastly, they are not 
 infrequently seated upon the surface of a mucous membrane, adher- 
 ing to it more or less intimately. 
 
 Should one of these pseudomembranes be stripped off. an ulcerate* 1 . 
 slightly bleeding surface is exposed, which clearly proves that we are 
 dealing not with a simple deposit, but a more profound lesion. 
 
 The detached false membrane is sufficiently resistant. It does 
 not disintegrate when agitated in water, thus being distinguished 
 from pultaceous layers or mucous accretions. It is dissolved by lime- 
 water and by sodium hypochlorite : its richness in fibrin explains why 
 it decomposes oxygenated water. 
 
 Under the microscope a false membrane is found to be composed 
 of anastomosed fibrinous threads, sending out prolongations which 
 attach themselves to the subendothelial tissues by a series of arcades. 
 This explains why the production is adherent. The fibrin appears 
 in the form of lamellae, compact masses, or spiral threads. In the 
 
180 INFECTIOUS DISEASES. 
 
 midst of the fibrin can be seen mucin, fat, altered cells, and in most 
 cases, numerous microbes. 
 
 The false membrane may grow by the addition of new layers of 
 fibrin and be reproduced when it is stripped off. The considerable 
 amount of fibrin which may thus be eliminated is not to be wondered 
 at. Dr. Dastre has demonstrated how rapidly this substance is pro- 
 duced in the organism. If the greater part of the blood of a dog 
 be defibrinated and again introduced into the vessels, it will soon be 
 found that the blood has become as rich in fibrin as normal. 
 
 When a false membrane occupies the surface of a mucous mem- 
 brane, that of the throat for instance, a time will come in fortunate 
 cases when the secretions of the subjacent glands will detach the 
 pseudomembrane and cause its exfoliation. The remaining adherent 
 particles will be removed by the phagocytes. This process may be 
 assisted by means of pilocarpine which, by stimulating glandular 
 secretion, hastens exfoliation of the pathological membranes. In 
 some instances the latter disappear in consequence of a histochemical 
 transformation. They undergo a granular or hyaline degeneration. 
 
 In other cases in tissues, and particularly in serous membranes, 
 the false membrane, instead of disappearing, becomes organized. The 
 fixed and the wandering cells proliferate, and the tissue becomes 
 vascularized. In this manner are formed adhesions which may 
 subsequently be absorbed, or undergo sclerotic transformation, or 
 become infiltrated with calcareous salts. 
 
 The production of false membrane must be considered as a phe- 
 nomenon of defensive reaction. It is a barrier opposed to the pene- 
 tration of microbes and toxins. In some cases it is a reinforcement 
 of tissues, preventing their destruction under the influence of patho- 
 logical causes. This is equally true as regards the false membranes 
 developing upon serous membranes. 
 
 In this mode of defensive reaction, as in other instances, excess is 
 often possible. The diphtheritic false membrane may, by reason of 
 its location, cause grave and fatal disturbances of a mechanical 
 order. The adhesions of serous membranes embarrass the move- 
 ments of subjacent viscera, give rise to deformities, compress impor- 
 tant organs or excretory passages, and thus bring in their train a 
 whole series of morbid manifestations. 
 
 Although the process is somewhat different, the production of 
 exudates rich in fibrin, as well as those produced by the pneumo- 
 coccus, may be compared to false membranes. The expression 
 
DEFENSES AND REACTIONS OF THE ORG iNISM. | >sl 
 
 "croupous pneumonia," a1 times applied to the pneumococcic inflam- 
 mation, suggests this analogy. We find \\\<- same pathogenesi 
 the pneumococcic exudates as for diphtheritic productions. The 
 investigations of C;iniot establish thai they depend upon micTobic 
 toxins. Their signification is identical in both cases. They are 
 lesions intended to protect Ihc organism againsl the penetration of 
 microbes and of toxins. < )n taking into accounl the oature of these 
 two sorts of exudates, we reach the conclusion, which ie equally thai 
 of Gilbert and Founder, that fibrin piny- a defensive rdle of consid- 
 erable importance. 
 
CHAPTER VII. 
 
 SUPPURATION. 
 
 Division of Pyogenic Microbes into Five Groups: The Habitual, the Specific, the 
 Accidental, the Vegetable, and the Protozoic Pyogenics. Relative Frequency 
 of Various Pyogenic Agents. Distribution of Pyogenic Microbes in and Outside 
 the Organism. Causes Favoring Suppuration: Importance of Number and 
 Virulence of Microbes; of the Mode of Entrance; of Previous Lesions. Gener- 
 alization of Suppurating Processes. Amicrobic Suppurations. Role of Soluble 
 Substances in the Production of Pus. Physical and Chemical Characters of Pus. 
 Mode of Development and Evolution of Suppurations. Hot and Cold Abscesses. 
 Suppuration in the Various Parts of the Organism. 
 
 From a histological standpoint, suppuration is essentially char- 
 acterized by the formation of an exudate containing very large 
 numbers of round cells, more or less similar to leucocytes. These 
 cells, therefore, became the first subject of research. Virchow 
 believed they were derived from the fixed cells of the inflamed tissue. 
 Cohnheim contended that pus corpuscles were nothing else than leuco- 
 cytes which had left the vessels by migration. Each of these con- 
 ceptions, as we shall see later, contained some part of the truth, 
 but they did not solve the problem. It was necessary to discover 
 the influences which caused the round cells to accumulate in an organ 
 or tissue and the conditions under which inflammation terminated 
 in suppuration. 
 
 During the epoch of Virchow it was admitted that any cause of 
 irritation could induce suppurative inflammation. Later, it was 
 asserted, on the contrary, that the various physical, mechanical, 
 and chemical excitants are incapable of producing pus unless the 
 foreign body introduced has special specific properties, viz., unless 
 it serves as the vehicle of pyogenic microbes. Caspard, as early as 
 1822, and after him, Gunther, d'Arcet, Castelneau, and, above all, 
 Sedillot, showed by experiments that, when injected beneath the 
 skin or into the serous membranes, pus can produce suppuration, 
 but did not demonstrate the specific nature of the process. 
 
 In 1872 Chauveau pointed out that the phlogogenic power of pus 
 depends not upon the serum, but upon the solid parts ; that the pus 
 corpuscles possess a special property, while the mineral substances 
 and the cells derived from the lymphatic glands are not capable of 
 
SUPPURATION. 183 
 
 giving rise; to suppuration. It was thus established thai all foreign 
 bodies are not pyogenic, 'the nature and cau ation of the prin 
 focus remained to be determined. 
 Lister admitted the role of germs without, however, believing thai 
 
 their intervention is indispensable, lie supposed thai suppuration 
 may be referable to other causes, for instance, the acl ion of chemical 
 agents or the influence of some nervous disturbance. From thai 
 epoch onward attention was called to the role of microbic agents. 
 In 1872, Klebs described a microsporon seplicum, capable of pro- 
 ducing pus. I" I<s7. r ) Bergeron noticed the presence of vibriorii in 
 the pus of acute abscesses. Kocher, studying a greal aumber of 
 abscesses, constantly found bacteria, and was thus led to the con- 
 clusion that there is probably no suppuration without microbes. 
 This was also the opinion of Cheyne, Koch, and Cornil, and it gen- 
 erally seems to be true in practise. 
 
 Under certain conditions almost all microbes are capable of exert- 
 ing pyogenic action. In order to facilitate description, howevei 
 may artificially divide them into four groups: First, the habitual 
 agents of suppuration, the pyogenics, properly so-called. Not that 
 they are found only in purulent foci — since the staphylococcus has 
 been met with in serous exudates, in pleurisies, in rheumatism, and 
 the same is true of the streptococcus — but because we consider that 
 their most characteristic property is the production of pus in the 
 organism. Secondly, unlike the common pyogenic microbes which 
 are abundantly distributed in nature, and often live as epiphytes or 
 saprophytes, there are specific pyogenics, always pathogenic and 
 always creating suppurative lesions. This group includes five spe- 
 cies: the diplococcus of cerebrospinal meningitis, the micrococcus of 
 gonorrhea, the bacillus of soft chancre, the bacillus of glanders, and 
 the bacillus of bubonic plague. The thud group comprises microbes 
 which are quite different from the preceding — specific agents which 
 habitually produce well-defined diseases, such, for instance, as the 
 microbes of typhoid fever or of influenza. These become pyogenic 
 only under special conditions, to be referred to later. Finally, in a 
 fourth division it is convenient to group those pyogenic agents which 
 do not belong to the class of bacteria. 
 
 The following table, although incomplete, comprises the principal 
 parasites capable of inducing suppuration: 
 
184 INFECTIOUS DISEASES. 
 
 1. Pyogenic Bacteria. 
 Staphylococci. 
 
 Staphylococcus pyogenes aureus (Rosenbach). 
 
 Staphylococcus pyogenes citreus (Passet). 
 
 Staphylococcus pyogenes albus (Rosenbach') . 
 
 var. : Staphylococcus salivarius pyogenes (Biondi). 
 Staphylococcus of Alrnquist. 
 
 Staphylococcus pyosepticus (Hericourt and Richet). 
 Staphylococcus epidermidis albus (Welch). 
 Microbe of the Biskra button (Duclaux). 
 Streptococci. 
 
 Streptococcus pyogenes (Rosenbach). 
 Streptococcus erysipelatis (Fehleisen). 
 Streptococcus articulorum (Loeffler). 
 Streptococcus pyogenes malignus (Fliigge). 
 Streptococcus septicus (Nicolaier and Guarnieri). 
 Streptococcus septopyemicus (Eberth and Wolff). 
 Streptococcus conglomeratus (Kurth). 
 Streptococcus ramosus (Roger and Weil). 
 Streptococcus of acute Bright's disease (Manneberg). 
 Streptococcus equi (Schutz). 
 Streptococcus ruber (Lundstrom). 
 
 Streptococcus of contagious mammitis of the cow (Nocard and Mollereau). 
 Streptococcus septicus liquefaciens (Babes). 
 
 Streptococcus pneumoniae (pneumonococcus of Talamon-Fraenkel) . 
 Micrococcus pyogenes tenuis (Rosenbach). 
 Micrococcus pneumoniae (Ortner). 
 Microbe of pneumonia of the horse (Schutz). 
 Other micrococci. 
 
 Micrococcus tetragenus (Koch, Gaffky). 
 Micrococcus gingivae pyogenes (Miller). 
 Micrococcus endocarditis rugatus (Weichselbaum). 
 Micrococcus subflavus (Fliigge). 
 Micrococcus pyogenes fetidus (Veillon). 
 Staphylococcus parvulus (Veillon and Zuber). 
 Diplococcus reniformis (Cottet). 
 
 Micrococcus of gangrenous mammitis of the lamb (Nocard). 
 Micrococcus of necrosis of the mouse (Koch). 
 Micrococcus of pyemia of rabbits (Koch). 
 Micrococcus of progressive suppuration of rabbits (Koch). 
 Bacilli. 
 
 Bacillus coli (Escherich). 
 
 B. lactis aerogenes (Escherich). 
 
 B. pyogenes fetidus (Passet). 
 
 B. burci. 
 
 B. endocarditis griseus (Weichselbaum)., 
 
 B. enteritidis (Gaertner). 
 
 Pyobacillus Fischeri. 
 Pneumobacillus (Friedlaender) . 
 
 B. meningitidis purulent® (Neumann and Schaeffer). 
 B. sycosis (Tommasoli). 
 Bacillus of noma (Schimmelbusch). 
 B. pyogenes soli (Bolton). 
 B. dentatis viridans (Miller). 
 Proteus Zenkeri. 
 
 Bacillus fetidus liquefaciens (Lenz). 
 B. nephritidis (Letzerich). 
 B. pulpaj pyogenes (Miller). 
 B. gingivae pyogenes (Miller). 
 B. capsulatus (Chiari). 
 Proteus vulgaris (Hauser). 
 Proteus mirabilis (Hauser). 
 Proteus pleomorphus (Karlinski). 
 Bacillus saprogenes II. (Rosenbach). 
 Bacillus saprogenes III. (Rosenbach). 
 B. pyogenes gazeigenes (Levy, Fraenkel). 
 B. perfringens (Veillon and Zuber). 
 B. ramosus (Veillon and Zuber). 
 B. serpens (Veillon and Zuber). 
 Bacillus fragilis (Veillon and Zuber). 
 
SUPPURATION. I -.", 
 
 B, fusiformia ( Veillon and Zuber). 
 
 B. furcosus (Veillon and Zuber). 
 
 Btreptobacillus pyogenes floccosus (P, Courmont and Cadi 
 
 2. Sit. en i« PyoOE [I BAC1 EM *. 
 
 I (iplocncctlS nil t'lK'.cl 1 1 1 1.T 1 i 1 1 n i i m " 1 1 1 1 1 i I, 
 ( lOMOOOCCllH. 
 
 Bacillus of soft ohanore. 
 
 I tacillus of glanders. 
 
 I tacillus of t lie bubonic plague, 
 
 :{. A.CCIDBNTA1 Pyoqj to Bacteria, 
 Bi anthracis. 
 I». of gaseous gangrene. 
 B. of symptomatic anthrax. 
 I '.. of hemorrhagic sei >\ Lcsemis . 
 B. of purulent rhinitis of the rabbil , 
 I'), of tuberculosis. 
 B. of pseudotuberculosis. 
 B. <>f influenza . 
 B. of typhoid fever. 
 
 4. Pyogenic Plants, 
 Streptothrix or oospora astcroides. 
 Strcptothrix or oospora Hofmani. 
 Streptothrix or oospora Gruberi. 
 Actinomyces (oospora bovis). 
 Oospora madurse. 
 Aspergillus fumigatus. 
 Penicillium. 
 Mucor (corvmbifer ?). 
 Botrytis (?) 
 Various yeasts: 
 
 Cryptococcus farcinosus. 
 
 Oidium albicans. 
 
 Trichophyton mentagrophytes. 
 
 Trichophyton felineum. 
 
 5. Pyogenic Protozoa. 
 Ameba coh. 
 Protozoon of variola. 
 Protozoon of varicella. 
 Protozoon of vaccinia. 
 
 1. Pyogenic Bacteria. 
 Staphylococcus. The type of the habitually pyogenic microbe is 
 represented by the staphylococcus pyogenes aureus. It was discov- 
 ered by Ogston in 1881, and fully described, in 1884, by Rosebach. 
 It is a facultative anaerobe developing readily in the majority of 
 media employed in bacteriology. Examined under the microscope, 
 the staphylococcus aureus, as well as albus and citreus. appears in 
 the form of small, rounded elements, measuring from 0.7 ft to 1.5ft. 
 The smallest elements are seen in old cultures, the largest in cultures 
 kept at 109.4 F. (43 C). In pus the cocci are disseminated in the 
 form of monococci or diplococci. In cultures they are generally 
 united in masses, presenting at times the aspect of a bunch of gr: 
 Hence, the name given to this species. More frequently, however, 
 these cocci are grouped in such a manner as to form large anasto- 
 mosed bands circumscribing empty spaces. 
 
186 INFECTIOUS DISEASES. 
 
 The chromogenic function which characterizes the staphylococcus 
 aureus has no specific value. This microbe ceases to secrete its 
 pigment when cultivated in the absence of air, or when small amounts 
 of antiseptic substances, such as antipyrin, are added to the medium, 
 or when the culture is exposed to strong sunlight. The different 
 staphylococci are, therefore, considered rather varieties of one spe- 
 cies. Owing to its greater power of multiplication and more ener- 
 getic pathogenic potency, the staphylococcus aureus is the leading 
 species. Next comes the staphylococcus citreus, followed by the 
 albus, whose cultures are not pigmented. Starting with the aureus, 
 it is easy to obtain the colorless variety. The reverse is less fre- 
 quently realized. Dr. Netter has, however, seen a staphylococcus 
 albus converted into aureus. 
 
 Streptococcus. A great number of streptococci have been de- 
 scribed. The present tendency, at least in France, is to regard them 
 as varieties of a single species. In fact, the different characters 
 described by authorities are rather uncertain and may disappear in 
 successive cultures. Researches in serotherapy, however, lead us 
 again to subdivide the group, since the serum of an animal immunized 
 against one variety does not combat infection by all streptococci. 
 The presence of micrococci in the form of chains had been noticed 
 by Coze and Feltz in various organic fluids. Pasteur and Doleris 
 subsequently discovered similar elements in puerperal infection. 
 Their presence in pus was pointed out by Ogston, then by Rosenbach 
 and Posset, who made a complete study and endeavored to differen- 
 tiate it from the streptococcus of erysipelas, discovered by Fehleisen. 
 The streptococcus develops quite readily in various media employed 
 for cultures. In agar-agar it generally vegetates in the form of very 
 small, rounded, somewhat hemispheroid, semitransparent, or opaque 
 white colonies. These colonies are generally isolated, except in very 
 active cultures in which they may become confluent. 
 
 The streptococcus is a facultative anaerobe. Some specimens 
 develop more luxuriantly without than with air and, withal, better 
 preserve their virulence and secrete more active toxins. Under the 
 microscope the streptococcus appears in the form of chains made up 
 of four to forty elements. The chains, which are rather short in 
 solid media, are much longer in liquid media, and particularly in 
 serum. Authorities have described different species of this coccus 
 according to cultural characters, morphology, and pathogenic action. 
 
 Behring first divides streptococci into two groups according as the 
 
SUPPURATION. 187 
 
 chains are long or short. The shorl one, streptococcus brevis, i- & 
 saprophyte] the long, streptococcus longus, i divided ■< fol 
 
 1 . S. rendering bouillon I urbid 
 
 S. of erysipelas. 
 S. pyogenes. 
 S. of anginas. 
 
 2. S. M«>(, rendering bouillon turbid, 
 
 «. Producing a mucous depo ii , 
 S. of phlegmon. 
 S. of bronchopneumonia. 
 S. of puerperal Lnfed ion. 
 
 b. Producing flocculi. 
 
 S. of scarlet fever (S. conqlomeratu 
 S. of gravr pycmi.M. 
 
 c. Producing large masses adhercnl in the walls "I" the tube. 
 
 S. of equine pneumonia . 
 
 It would be more rational to base a classification upon results 
 obtained by inoculations into animals than upon modifications 
 observed in the form of the elements and appearance of the cultures. 
 Under these conditions four varieties of streptococci should be 
 admitted: saprophytic, septicemic, pyogenic, and erysipelatogenic. 
 Experimental and clinical studies demonstrate, however, thai the 
 pathogenic varieties easil} r fall into the rank of saprophytes. Recip- 
 rocally, most of the non-virulent cultures are capable of exaltation- 
 The microbe first becomes capable of producing pus, then of giving 
 rise to erysipelas, and, finally, to septicemia. This result having 
 been verified by many authorities, has led to the admission of two 
 principal species, pyogenic and erysipelatogenic, in which all the 
 other varieties have been included. 
 
 Pneumococcus. The belief that the pneumococcus is related to 
 the streptococcus has gradually gained ground. Some bacteriolo- 
 gists even co'nsider it to be a variety of true streptococci. In support 
 of this view, it ma} r be recalled that there are certain microbic forms 
 constituting transitions between the extreme types. Until the con- 
 trary is proven, however, it is more rational to consider the pneu- 
 mococcus of Talamon-Fraenkel as a different species. Its pyogenic 
 role needs no further demonstration. There is already abundant 
 observation showing that this microbe is capable of producing sup- 
 puration in the lungs or elsewhere. Contrary to an opinion formerly 
 advanced, it is now known that postpneumonic abscesses may be 
 created under its influence without the co-operation of any other 
 microbe. 
 
 There are other pyogenic micrococci, among which the microc<: 
 
188 rJV FEC TIO US DISEA SES. 
 
 tetragenus occupies an important place. Chauffard and Ramond 
 
 believe that it can produce septicemias, and I have frequently found 
 it in cases of sore throat, in which, however, it was associated with 
 various other microbes (p. 44). Being almost constantly present 
 in the buccopharyngeal cavities, the tetragenus is found in the 
 abscesses developing in this region. It is met with particularly in 
 dental abscesses, cervical adenites, otites, mastoidites, suppurations 
 of nasal origin, pulmonary abscesses, purulent bronchitis, and in the 
 pus of tuberculous cavities. Karlinski has found it in tubercles, and 
 Babes in pyohemia, I have found it in the thick, yelloAv discharge 
 of an otitis developed in a child convalescent from scarlatina. 
 
 The other pyogenic micrococci are far less important. 
 
 Pyogenic Bacilli. The bacillus coli unquestionably heads the list 
 of pyogenic bacilli. Abundantly distributed throughout the alimen- 
 tary canal, it is naturally met with in suppurations occurring in and 
 around the digestive tract and aroimd the genito-urinary apparatus. 
 It may, however, easily migrate from these primary foci and induce 
 secondaiy suppurations in distant parts, or even a general infection 
 — a pyemia. 
 
 The morphology of this bacillus is very variable. It most fre- 
 quently occurs in the form of small rods, with rounded ends, measur- 
 ing from 2/j. to 4/* in length and 0.7// to Iju in breadth. It some- 
 times appears in the form of oval elements, which at first may be 
 mistaken for micrococci. At times it is isolated, at others grouped 
 in pairs, or it becomes elongated to such an extent as to form fila- 
 ments which are often constricted at several points in its length. 
 Finally, if we add that there are motile and non-motile forms ; that 
 the appearance of cultures in agar-gar and gelatin and upon potato 
 is not uniform; that the so-called specific characters are inconstant 
 and variable; that some samples ferment sugar and others do not, 
 and that certain cultures produce indol, others furnish none, it will 
 be understood how delicate interpretation becomes. With the typical 
 colon bacillus Gilbert has grouped and described the paracolon bacilli 
 which present pronounced deviations from the classical type. It is 
 certain that the group of colon bacilli includes species which will 
 some day be differentiated. The reason division is not more ad- 
 vanced is that none of the properties seem to be absolutely constant. 
 It is convenient, therefore, to include the various forms under the 
 same denomination, as is done with the streptococci. 
 
 Among the bacilli at present believed to be related to B. coli there 
 
SUPPURATION. 189 
 
 is the 11. lactis aerogenes, discovered by Eschcrich in the stoolf ol 
 infants. Close to this bacillus standi the pneumobacillu of Fried- 
 laender. Between these two organisms pronounced analogies may 
 readily be observed. The presence of a capsule i a character too 
 contingent to be of sped lie value. The I wo microbe* cannot b< 
 better differentiated by their action upon animals, since we have 
 shown that, contrary to classical opinion, the bacillus of Friedlaender 
 is pathogenic for the rabbit. Hence, the attempl of eminenl scien- 
 tists, such as Denys, to regard the two bacilli as identical. The 
 question is and will long remain a delicate one. Therefore, withoul 
 pretending to offer a definite solution, I have 1 hough 1 if sufficienl to 
 point out the analogies of I he two microbes and to recall the pyogenic 
 power of the pneumobacillus. Akin to this microbe is the one 
 described by Passet under the name pneumobacillus dhnlicher, which 
 was found by the author in an abscess and which produces suppura- 
 tion in animals, and, finally, the encapsulated bacillus which Chiari 
 detected in suppurative nephritis, prostatites, otites, and menin- 
 gites. 
 
 Anaerobic Pyogenic Bacteria. While common suppurations are 
 generally clue to aerobic microbes, the anaerobic seem to piny a 
 considerable role in the development of gangrenous or putrid ab- 
 scesses and phlegmons. Levy isolated from a gaseous abscess a small 
 anaerobic abscess which he failed to cultivate beyond the first gen- 
 eration. This is probably the same microbe which Fraenkel again 
 met with in three cases. Inoculation of cultures gave rise to gaseous 
 gangrene in animals — a new illustration of the relationship existing 
 between suppuration and gangrene. 
 
 Examining sixty samples of pus, Lubinski found anaerobic bacilli 
 twice. Similar findings have been made by various authorities who 
 are at present inclined to admit that anaerobics play the principal 
 part in the development of suppurations in the urinary apparatus 
 (Albarran, Cottet), genital apparatus, at least in women (Veillon. 
 Zuber, Dujon, Halle), and certain portions of the alimentary canal 
 (Veillon and Zuber). 
 
 One of the most important bacilli isolated by experimenters seems 
 to be the B. ramosus. which is supposed to be the chief agent in 
 appendicitis. In conjunction with it we must mention the B. per- 
 fringens, analogous to or identical with the anaerobic bacillus of Levy 
 and Fraenkel; the B. fusiformis. the B. serpens, the B. jragilis. the 
 B. furcosus. and the staphylococcus parvulus. A detailed description 
 
1 90 INFECTIO US DISEASES. 
 
 of all these species will be found in the interesting memoire of Veillon 
 and Zuber. 1 It will suffice to note here that these various agents, 
 when inoculated into animals, give rise to abscesses or phlegmons. 
 Some of them, only slightly noxious when alone, become highly viru- 
 lent when associated with other species. Such is the case with B. 
 serpens when it is inoculated along with the B. ramosus. 
 
 Among the anaerobics which intervene in suppurations of the 
 urinary passages the most interesting is the diplococcus renijormis 
 (Cottet), which produces urinary and periurinary abscesses, pyone- 
 phroses, and cystites. By its morphological characters it resembles 
 the gonococcus, with which it has probably often been confounded. 
 
 2. Specific Pyogenic Bacteria. 
 
 Five microbes at present make up this group. They differ from 
 the agents which we have thus far studied in that they always give 
 rise to suppuration and that this suppurative process has special 
 characters previously established by clinical observation. Bacte- 
 riology has done no more than confirm the data of clinical experience. 
 
 The microbes of cerebrospinal meningitis, gonorrhea, soft chancre, 
 glanders, and bubonic plague, although pyogenics, deserve to be 
 grouped in a special class. The gonococcus resembles common pyo- 
 genics in some respects. Like the latter, it is said to be capable of 
 vegetating as an epiphyte upon healthy mucous membranes. From 
 this point of view, the bacillus of soft chancre or bacillus of Ducrey 
 occupies a higher rank. Finally, the bacillus of glanders assumes 
 a position of transition between the pyogenics and the specific agents, 
 such as the tubercle bacillus. 
 
 3. Bacteria Accidentally Pyogenic. 
 
 Highly differentiated microbes, capable of producing well-defined 
 diseases, give rise to no more than abscesses when they are atten- 
 uated or inoculated into animals not very sensitive by nature or 
 rendered artificially more or less immune. Such, for instance, is the 
 case with anthrax, the inoculation of which into old rats causes only 
 an abscess. The same is true with regard to the virus of gaseous 
 gangrene or symptomatic anthrax when inoculated into animals 
 which have been subjected to incomplete vaccinations. An analo- 
 gous example is furnished by the microbe of chicken cholera, which 
 
 1 Veillon and Zuber. Recherches sur quelques microbes strictement anaerobies. Arch. 
 de med. exper., 1898, p. 517. 
 
SUPPURATION. 19] 
 
 causes a speedily fatal septicemia in chicken and rabbits, bul pro- 
 duces only a more or less extensive uppural ion in guini while 
 in man it gives rise to qo inure than a circumscribed ab c< . a the 
 author was able to observe in consequence of an accidental inocu- 
 lation. 
 
 We need hardly recall I ba1 I he bacillus of I uberculosis may become 
 pyogenic. Everyone is acquainted with the frequency of cold, 
 cutaneous, osseous, or articular suppurations in which no other para- 
 site is found. Whal is accomplished by Koch's bacillus U equally 
 realized by the bacillus of pseudotuberculosis. Either tubercles 
 or pus is obtained, according to the anima] experimented upon or 
 the mode of introduction. 
 
 Of all accidental pyogenic microbes the mosl interesting i- that 
 of typhoid fever. Numerous experimental researches have demon- 
 strated (hat this microbe can produce abscesses in animals. The 
 pure bacillus of Eberth lias been met with in a certain number of 
 suppurative lesions consecutive to typhoid fever. Dehu, in his 
 thesis (1893), collected forty observations. According to Chante- 
 messe and Widal, these suppurations are most frequently observed 
 in the bones; then, in order of decreasing frequency, in the meninges, 
 pleura, peritoneum, and S} r novial membrane. The thyroid and the 
 testicles are the two glands in which it is not infrequently localized. 
 The spleen is the only visciis in which such process lias been noted. 
 The course is at times acute, but more frequently its evolution is 
 slow. In the latter instance we have to deal with cold suppurations. 
 Such is the case particularly in osteomyelitis with successive exacer- 
 bations, which are prolonged for years, and the same is true in tuber- 
 culous osteitis. These facts should be remembered, as they are not 
 extremely rare. Their complete history will be found in the work 
 of Chantemesse and Widal. 1 
 
 4. Vegetable Pyogenic Parasites. 
 
 Several species of streptothrix or oospora are capable of producing 
 suppuration in man and animals. The most important is incontest- 
 able- the oospora astcroides, discovered by Eppinger in a cas 
 meningitis and again found under analogous conditions by Almquist. 
 The same parasite has been seen by Ferre and Faguet in a cerebral 
 abscess; by Sabrazes and Riviere in the sputa of a patient, in the 
 
 1 Chantemesse and Widal. Des suppurations froides consecutive a la fievre typhoide. 
 Soeicte medicate des hopitaux. November 24. 1S93. 
 
192 IXFECTIO US DISEASES. 
 
 pus of subcutaneous abscesses, and in abscesses of the brain and 
 kidney. We will again refer to the group of oospora in treating of 
 actinomycosis. 
 
 Special mention is due to a mucor found by Paltauf in a patient 
 suffering from a strange affection characterized by pharyngolaryngeal 
 phlegmon, pneumonia, and intestinal ulcerations. The parasite that 
 had given rise to these various lesions was analogous to the mucor 
 corymbifer whose pathogenic action upon animals was first shown 
 by Lichtheim. 
 
 The pathogenic properties of yeasts and of oidium albicans will 
 be discussed in a special chapter. 
 
 Finally, more highly organized parasites, such as the tricophytons, 
 may also induce suppurations. Rosenbach admits seven pyogenic 
 species of them, among which the most important are the T. menta- 
 grophytes in man and in the horse, and the T. jelineum in the cat 
 and in children. 
 
 It is well to add that the majority of pyogenic plants are capable 
 of producing infectious nodules comparable to tuberculous granula- 
 tions. Such is the case with regard to the mucorinse, the aspergillus, 
 the saccharomycetes, and the oidium. These various parasites will 
 again be referred to in the chapter on pseudotuberculoses. Some of 
 them may even produce genuine tumor. It will suffice to mention 
 the actinomyces. Here, then, we have to deal with a series of facts 
 which establish numerous transitions between lesions seemingly very 
 widely apart — suppurations, granulations, and neoplasms. 
 
 5. Pyogenic Animal Parasites. 
 
 The study of diseases suffered by inferior animals has drawn the 
 attention of observers to the pathogenic role of the protozoa. The 
 presence of infusoria and flagellatse in the suppurations occurring in 
 man has long been noted. The balantidium coli, for instance, in the 
 suppurative lesions of the intestine; the trichomonas vaginalis in 
 vaginal suppurations and in chronic affections of the digestive canal. 
 It may well be questioned, however, whether these parasites are not 
 accidental guests by no means pathogenic. 
 
 The arneba coli, an animal parasite, is held by many observers 
 to be the agent of one of the clinical types of dysentery. What is 
 of more direct interest for our subject is the fact that this parasite 
 is at times found unassociated with other organisms in hepatic 
 abscesses consecutive to dysentery. With Dr. Peyrot, the author 
 
8UPPUBA ri os. 193 
 
 observed a c.'isc of this kind, [t i a qua tion, however, whether the 
 pus did not at some time contain pyogenic bacteria which had 
 disappeared. The interesting experiments of Marchoux eem to 
 establish that the amebaof dysentery is really capable of creating 
 suppuration. 
 
 Relative Frequency of the Various Pyogenic Agents. 
 
 Anions the pyogenic microbes above described the mosl widely 
 distributed arc the staphylococci and the streptococci. I' is noi 
 rare, however, to find several bacteria together in the same focus. 
 Ogston studied sixty-nine abscesses and detected the simultaneous 
 
 presence of two species in sixteen instances. Zuckermann found 
 records of 495 bacteriological examinations of ho1 abscesses. In 70 
 per cent, of the cases the staphylococcus bad been found; in 16 per 
 cent, the streptococcus, and in 5.5 per cent, both of these species. 
 Then followed the bacillus pyogenes fetidus, the bacillus jii/utjcncs- 
 tenuis, the tetragenus, etc. 
 
 The association of several pj^ogenic microbes seems to result in 
 an aggravation of the suppurative phenomena. Suppose two pyo- 
 genic microbes attenuated to such an extent that each, injected alone, 
 produces no disturbance. If they are united, the result of their 
 simultaneous inoculation is the formation of an abscess. 
 
 By mixing a harmless sample of the staphylococcus with a sapro- 
 phyte or an attenuated culture of streptococcus, suppuration is 
 obtained. By study of the purulent focus, however, Trombetta 
 recognized that the focus soon became monomicrobic. The staphy- 
 lococcus prevailed, and soon no other microbe was discoverable. 
 This fact is in harmony with the findings of clinical observation. A 
 focus may at first contain one pyogenic species, and at the end of a 
 certain period of time, another. Such is particularly the case in 
 otitis. Whatever may have been the microbe found at the beginning 
 the staphylococcus is almost always found at a later period. Thus, 
 there are microbes which start a suppuration and microbes which 
 maintain it. If it be further remembered that simple saprophytes 
 play an auxiliary role in the production of suppurative phenomena, 
 it will readily be understood why all purulent foci should be protected 
 against external germs, even apparently inoffensive ones. 
 
 The true pyogenic microbes, notably the staphylococcus and the 
 B. coli, are abundantly distributed in nature, but are epiphytes 
 rather than inhabitants of the inorganic world. They are. therefore, 
 
 13 
 
194 INFECTIO US DISEASES. 
 
 found mostly in crowded neighborhoods, in hospital wards, and in 
 water polluted by men and animals. Once thrown into the external 
 world, these pyogenics would soon destroy each other if they were 
 not protected by the organic materials in which they reside. Pus, 
 mucus, fecal matter, etc., shield them against causes of destruction, 
 especially against the influence of the sun. These facts must be 
 taken into serious account, since in experiments it is the resistance 
 of pyogenic germs derived from cultures, and, consequently, placed 
 under less favorable conditions, that is studied. When they resist 
 cosmic agents and struggle for life against other microbes, the pyo- 
 genics gradually lose their aptitude to thrive in living organisms, 
 become attenuated, and finally assume the rank of simple sapro- 
 phytes. This is what happens, for instance, with the strepto- 
 coccus. 
 
 The staphylococcus aureus has been detected in the air (Fraenkel), 
 dust, soil (Lubbert), and water (Ullmann). It seems to be more 
 resistant than the streptococcus. The latter cannot live more than 
 five days in sewer water, while the former is still living at the end of 
 twenty days (Strauss and Dubarry), or even several months (Meade 
 Bolton). The tetragenus resists eighteen to twenty days. The 
 author has several times found this microbe in the air, a fact well 
 in harmony with its frequent presence in the buccal cavity. 
 
 The pneumococcus is far more delicate than the preceding 
 microbes. Except when it is protected by the mucus of expec- 
 torations, it becomes attenuated and soon perishes. 
 
 The proteus vulgaris and mirabilis and, above all, the bacillus coli 
 are also among those pyogenics which are frequently found outside 
 the organism. The last-named microbe is widely distributed and 
 can vegetate in water for months. 
 
 These microbes, though capable of living in the external world, are 
 nevertheless parasites, and are mostly found in man and animals. The 
 S. aureus normally vegetates on the skin. It may also be met with 
 in the mouth and in the nasal mucus. Escherich has detected it in 
 the stools of healthy children, a result due to contamination of the 
 mother's milk at the nipple. The author always found the S. albus 
 in milk taken under ordinary conditions, while this secretion was 
 found to be sterile when obtained with necessary precautions. 
 
 Streptococci may be detected in the same localities as staphylo- 
 cocci, but the former are inclined to abandon the exposed parts of 
 the organism. They are seldom encountered in the skin. Their 
 
SUPPURATION. I!).-, 
 
 seat of predilection is the buccopharyngeal cavity, where they are 
 constantly present. They may invade the digestive trad and the 
 genital organs of women in the lower pari of the vaginal canal. 
 This last localization explains their frequency in the lochia of women 
 
 in nowise in fee led. 
 
 The tetragenus and pneumococcus are likewise found in the mouth. 
 The pneumococcus is met with in aboul one-fifth of all subjects. 
 
 No wonder, therefore, thai the inoculation of saliv;i into the rabbit, 
 and especially the mouse, may give rise to a speedily fatal septicemia. 
 The infection thus produced, which w;is discovered by Pasteur and 
 well studied by Sternberg, is due, as the researches of Fraenkel have 
 established, to the agent of fibrinous pneumoni.i. 
 
 The B. coli is also widely distributed from the mouth to the ami-. 
 whence it enters the genital organs. It is also found in all animals. 
 Hence its constant presence in milk. In fact, the researches of 
 Wurtz and Leudet tend to establish that the lactic ferment is nothing 
 else than a variety of colon bacillus. 
 
 From this brief exposition, it may be seen that the pyogenic 
 microbes are everywhere within and external to our bodies. This 
 fact points to a rather restricted action of microbes and re-establishes 
 the role of the organism in the development of morbid phenomena. 
 
 We are thus led to consider how and. why the pyogenic microbes 
 invade the human organism and how they, at times, become virulent. 
 
 Auxiliary Causes of Suppuration. 
 
 The mode of development of a suppuration is easily accounted for 
 when the process is induced, not by microbes which we habitually 
 harbor, but by exalted germs of diseased animals and men. The 
 question, then, is to learn how this primary focus, which directly or 
 indirectly contaminates other individuals, originated. In many cases 
 suppuration is the result of a traumatism which, producing a solution 
 of continuity, offers an entrance to these microbes. The latter find 
 a favorable medium in the altered tissues and rapidly develop. 
 
 It must be recognized, however, that traumatism does not always 
 suffice to give rise to suppuration, even in the absence of antiseptic 
 precautions. The experiments of Garre, Schimmelbusch. and Wash- 
 nuith established that pyogenic micro-organisms can penetrate into 
 the skin of man and animals in the absence of the slightest cutaneous 
 abrasion. 
 
 At the present day it is a matter of common knowledge that a 
 
196 IXFECTIO US DISEASES. 
 
 pyogenic microbe introduced into the organism docs not necessarily 
 give rise to symptoms. It may be rapidly destroyed. If, in other 
 cases, it succeeds in doing mischief, it is owing to a series of secondary 
 causes, soine of which depend upon the microbe, others upon the 
 invaded organism. 
 
 On the part of the microbe we have to count with the number, 
 virulence, and mode of hit roduction. Fehleisen long since recognized 
 that small amounts of staphylococci and streptococci may be injected 
 beneath the skin without producing any lesion. To produce an 
 abscess he had to employ 1 c.cm. of the culture. If 5 c.cni. were 
 introduced, the animal died in eighteen or thirty hours without any 
 suppurative manifestation. According to Odo Bujwid, suppuration 
 does not appear when 1,000,000,000 staphylococci are injected 
 into the rabbit, the rat, or the mouse. It may happen that even 
 8,000,000,000 are insufficient for the rabbit, while this amount is 
 always fatal for the rat. 
 
 The value of these figures should not be exaggerated. The results 
 evidently depend upon the degree of virulence of a given sample, 
 since it has long since been well known that microbes possess no 
 fixed, definite potency. When pyogenic microbes are of moderate 
 virulence, they produce pus; when highly exalted, their inoculation 
 causes general infection, and the animal speedily succumbs to septi- 
 cemia, and microscopic examination reveals no appreciable lesions 
 in the cadaver. On the other hand, when they are too attenuated, 
 they often prove incapable of giving rise to the slightest lesion, even 
 though they are introduced in considerable numbers. The results 
 vary not only with the number and the degree of virulence of the 
 microbes, but also with the mode of entrance. Experimenting upon 
 rabbits, Herman discovered, for instance, that the peritoneum is 
 twenty times more resistant than other parts to inoculations of 
 staphylococcus. 
 
 When directly injected into the blood, the pyogenic microbes 
 become localized in various organs and there produce purulent foci. 
 These localizations may be favored by visceral lesions. If, for 
 instance, the cardiac valves are the seat of traumatism, an ulcerative 
 endocarditis is obtained ; if a fracture has been produced, the result 
 will be an osseous suppuration. It is possible to thus create artifi- 
 cially points of fixation for the agents in circulation. Inspired by 
 this fact, Dr. Fochier attempted to create aseptic foci designated by 
 the name of abscesses of fixation. In his opinion, these foci were 
 
SUPPURATION. 197 
 
 calculated 60 attract the microbes to those poinl where they would 
 
 do little, if any, harm to the organic m, 
 
 Tissues in active growth may likewise represenl point* of attrac- 
 tion for agents in circulation, [ntravenous injection of pyogenic 
 microbes may induce osteomyelitis in young animal . a ha been 
 shown by Etodet experimenting with the staphylococcus, and by 
 Courmont and Jaboulay, and Lannelonge and Achard with the 
 streptococcus. 
 
 Role of Nervous Alterations. Simple seel ion of the sciatic n< 
 without inoculation of microbes beneath the skin, is no1 followed by 
 trophic ulcerations, at least in the rabbit. Such is not the case with 
 the guinea-pig. In this animal a gangrenous edema of the lower 
 segments of the limb of the operated side supervenes some time after 
 the excision of the nerve. The tissues swell uwd are infiltrated with 
 pus, then disintegrate and leave the skeleton denuded. The animal 
 finally dies. The fact is that the ulcerations produced by the wound 
 upon the surface of the skin served as portals of entrance to the 
 microbes, and the germs rapidly multiplied in those tissues whose 
 vitality was diminished and gave rise to extended injury. 
 
 The sciatic is a mixed nerve — motor, sensory, and vasomotor — 
 and certain of its fibres seem to have antagonistic actions upon a 
 local infection. In order to prove the role devolved upon the various 
 parts of the nervous system, it was necessary to operate upon nerves 
 performing a special function. I therefore first studied the influence 
 of the sympathetic nerve. 
 
 Brown-Sequard long since had established experimentally that 
 section of the great sympathetic favored the healing of wounds. 
 Operating upon rabbits, the author introduced from six to seven 
 drops of a streptococcus culture into the two ears at the same point 
 — i. c, in the middle portion, a little to the inside of the central 
 artery. Immediately after the inoculation the author extirpated 
 the superior cervical ganglion on one side. At the end of twenty-four 
 hours the operated ear was found hot and infiltrated with serum. 
 The inflammation increased and reached its maximum toward the 
 third or fifth day. From this moment onward the aspect of the two 
 ears completely changed. On the operated side the lesions resolved : 
 on the intact side they were aggravated. Toward the sixth or 
 eighth day the nerveless ear resumed its normal appearance, while 
 on the intact side the lesions grew worse, infiltration being enormous, 
 abscesses and phlyctenule having developed, as a result of which a 
 
1 98 IXFECTIO US DISEASES. 
 
 part of the ear sloughed and perished. The edematous 'infiltration 
 generally disappeared toward the fifteenth day, persisting, in some 
 instances, for twenty and even fifty days. 
 
 In these comparative experiments section of the sympathetic nerve 
 produces a double effect. It gives rise to congestion in the operated 
 ear, and to anemia in the intact ear. The results thus become 
 extremely clear owing to the production of contrary vasomotor 
 modifications on the two sides. 
 
 These experimental facts remind us of certain clinical observations. 
 It is well known that heat is emploj^ed to heal certain suppurative 
 inflammations. Active congestion, whether produced by hot appli- 
 cations or by vasomotor dilatation of the arteries, favors recovery. 
 It may, therefore, be concluded that active congestion is favorable 
 to the healing of a local lesion, while passive congestion renders such 
 lesion more serious and tends to produce gangrene. Similarly, in a 
 cardiac patient in the stage of asystole, the slightest lesion results 
 in suppuration or sphacelation. Finally, suppression or diminution 
 of the blood supply, as is realized by ligation of arteries, favors the 
 development of local lesions. 
 
 The influence of sensory nerves upon the development of suppu- 
 ration can easily be demonstrated by sectioning the amiculocervical 
 nerve of a rabbit and injecting streptococci beneath the skin of both 
 ears. In order to obtain clear results, use should be made of an 
 agent of moderate power which gives rise only to a small, circum- 
 scribed abscess on the intact side. The ear deprived of the nerve 
 becomes the seat of an intense lesion — i. e., a very marked edema, 
 phlyctenular filled with a serous fluid, and abscesses, which may 
 result in mutilation or perf oration of the organ. 
 
 Role of Previous Local Lesions. The presence of foreign bodies 
 in a wound exercises a harmful influence upon the evolution of the 
 process. This fact is one of those proved beyond all doubt by clinical 
 observation. In many cases the seemingly endless process of sup- 
 puration has been abruptly stopped by the extraction of a piece of 
 cloth, a fragment of a bullet, or a splinter. 
 
 The harmful influence of caustic or irritant substances upon inflam- 
 matory processes is more marked. The author has tried, with Dr. 
 Josue, the effect of trimethylamin and of carbolic acid. With an 
 amount of colon bacillus sufficient to produce only a small abscess 
 in the controls, half a gram of trimethylamin was injected beneath 
 the skin of the thigh of a rabbit . The result was a phlegmon invad- 
 
SUPPURATION. 199 
 
 ing the cellular (issue of the abdomen, The effeel of carbolic acid 
 is even more manifest. This antiseptic ub tance, far from com- 
 bating infectioD and preventing suppuration, favor them. Having 
 injected subcutaneously, as above, a solution of 5 eg. of carbolic acid 
 in I c.cm. of water, then 0.5 c.cm. of a culture of colon bacillus in 
 bouillon, we noticed the production of an enormous diffuse phlegmon 
 infiltrating the whole thigh and the lower half of the abdomen. It, 
 however, only 2 eg. of carbolic acid is injected, no resull what 
 is obtained. This is a fresh demonstration of the harmful action of 
 strong antiseptics. 
 
 This noxious influence of chemical substances upon the vitality 
 of tissues is equally exercised by disease. The (issues already altered 
 by a- morbid process are exposed to the invasion of pyogenic microbes. 
 It will suffice to remember the purulent foci developing in neoplasms 
 or in the lungs during a pneumonia or tuberculosis. The importance 
 of these secondary infections is well known, as they play a consider- 
 able role in the production of cavities and explain the hectic phe- 
 nomena observed in the third stage of consumption. 
 
 Influence of the General State. Individual predisposition and 
 resistance largely depend upon the general state of the organism. 
 It is an undoubted fact that suppuration is more liable to develop 
 in certain subjects than in others. The slightest abrasion in them 
 occasions an abscess or a phlegmon. Even without any solution of 
 continuity, a contusion or friction suffices to permit the penetration 
 of germs. In other cases, in the absence of any appreciable cause, 
 cutaneous suppurations, acne, abscesses, furuncles, and anthrax 
 appear, and sometimes repeatedly. 
 
 These transitory or permanent predispositions depend upon either 
 a diathetic condition, an inherited or acquired mode of nutrition, or 
 a series of causes the influence of which has been conclusively estab- 
 lished by numerous clinical and experimental facts. Such are over- 
 work, exposure to cold and heat, starvation, cachexias, and, above 
 all, intoxications. 
 
 We have an interesting illustration of this fact in mercurial stoma- 
 titis. The buccal lesions are not due to the elimination of mercury. 
 On the contrary, the mercury acts by creating a morbid predispo- 
 sition and by diminishing the resistance of the tissues. Hence, the 
 rapid development of pyogenic microbes and the exaltation of their 
 virulence, which explains why mercurial stomatitis may become con- 
 tagious. Diday reported the history of a man who communicated 
 
200 INFECTIOUS DISEASES. 
 
 this affection to his wife. Transmission of exalted bacteria had 
 occurred in this case. 
 
 The cutaneous manifestations of bromism and iodism are likewise 
 accounted for by the development of pyogenic microbes present upon 
 the surface. The phenomena are, however, more complex in this 
 instance, as the concomitant gastrointestinal disturbances must also 
 be taken into account. In fact, Dr. Fere has established that these 
 infectious manifestations may be diminished and suppressed by 
 means of intestinal antisepsis. 
 
 Those chemical substances which diminish the alkalinity of the 
 blood seem to favor suppuration; but the results are not sufficiently 
 conclusive. On the other hand, some authorities maintain, though 
 their conclusions have often been contradicted, that the administra- 
 tion of sodium bicarbonate for some length of time renders the 
 animals more resistant by increasing the alkalinity of their humors. 
 
 There is a group of substances w r hich favor the development of 
 pyogenic agents. We refer to ferments. The author has shown 
 that the attenuated streptococcus recovers its virulence when it is 
 injected with papain. What the products of highly organized plants 
 do, microbic products, ferments, and ptomains can also realize, and 
 even more readily. Grawitz has thus recognized that the simulta- 
 neous introduction of cadaverin and staphylococci or streptococci 
 gives rise to a violent phlegmon, the alkaloid and the microbe having 
 powerfully aided each other. 
 
 The resistance of the organism to pyogenics also diminishes as a 
 result of nutritive disturbances suffered in grave diseases. Con- 
 valescents from typhoid fever, for instance, often develop manifold 
 suppurations, abscesses, and furuncles, which may adequately be 
 accounted for by insufficient nutrition of the subject. 
 
 Finally, it is interesting to note that quantitative modifications 
 of the blood seem to be without influence. Even abundant and 
 repeated general bleeding is ineffective. 
 
 Generalization of Suppurating Lesions. 
 
 We have thus far studied the causes which explain the develop- 
 ment or aggravation of a purulent focus. It is evident, however, 
 that suppuration does not always remain circumscribed, and that 
 the microbes may emigrate and give rise to visceral colonies. Why 
 are not the germs which enter the circulation destroyed by the 
 protective organs ? Rhine justly attributes this failure to a general 
 
SUPPURATION. 201 
 
 decline of the organism, due to the effect of microbic prod 
 mated at the primary Focus. As microbic 3ecretioi with the 
 
 samples employed and the aptitude of the organism to neutralize the 
 toxins differs from one individual to another, il is readily conceived 
 why the process sometimes remains local and al others becomes 
 generalized. 
 
 Of the microbes which pass into the general circulation, some are 
 destroyed l>y Hie leucocytes, some are eliminated, and others remain 
 in the tissues. The elimination is mainly effected by the kid] 
 and the skin. Brunner, Eiselsberg, Gaertner, Tizzoni; Preto, Nan- 
 notti, and Baciocchi have detected the staphylococcus in the urine 
 and sweat in cases of general infect ions, even in benign suppurations. 
 The latter instance is of great interest, as it tend- to prove that 
 pyogenic microbes easily penetrate into the organism, bul are quickly 
 destroyed or eliminated. Elimination through the emunctories 
 seems to be achieved without any inconvenience to the eliminating 
 organs. It is a true, natural, therapeutic procedure. 
 
 Such is not always the course of events, however. The microbes 
 that have found access to the organism are not invariably destroyed 
 or eliminated, and, if very virulent, they then are capable of causing 
 a fatal septicemia. If they are less active they create purulent foci, 
 which, according to their number and locality, may resolve or prove 
 fatal. The formation of visceral foci may, therefore, be considered 
 as a last defensive measure on the part of the organism. Numerous 
 clinical facts demonstrate that in puerperal women, for example, the 
 development of a phlebitis or of a periuterine phlegmon coincides 
 with amelioration of the puerperal fever and a retrogression of alarm- 
 ing phenomena. The localization may become very grave of itself. 
 but the immediate accidents are, in part, avoided. 
 
 Non-microbic Suppurations. 
 
 We have seen that most of the known microbes may. under cer- 
 tain circumstances, give rise to the formation of a purulent focus. 
 We now come to the question whether suppuration is ever possible 
 without the intervention of animate agents. ITueter and his 
 ciples were the first to experiment with aseptic substances by 
 injecting a certain amount of a solution of silver nitrate and of 
 zinc chloride into the subcutaneous cellular tissue. No abscess fol- 
 lowed, and the authors concluded that there is no pus without 
 microbes. 
 
202 IXFECTIO US DISEASES. 
 
 In 1883 Straus published the result of forty experiments made 
 upon rabbits, guinea-pigs, and rats. He had introduced beneath the 
 skin the most varied substances, such as croton oil, sterilized water, 
 mercury, etc. and in no case did he observe suppuration, save when 
 microbes had accidentally penetrated. Analogous results were ob- 
 tained by other experimenters. In 1885 the Medical Faculty of 
 Berlin made this a competitive question. Klemperer secured the 
 prize. In his various experiments intense inflammation, or serous 
 exudation, or even coagulation necrosis was observed, but there was 
 no pus. Zuckermann experimented with no less than thirty-one 
 substances, and never observed pus without microbes. 
 
 So many experiments performed by able scientists would seem 
 sufficient to settle the question, but we shall now cite another series 
 of researches leading to a diametrically opposite conclusion. Riedel 
 obtained aseptic suppuration by injecting mercury into the knee- 
 joint of a rabbit, and Cohnheim, by introducing croton oil beneath 
 the skin of a dog. Councilman took up the question and resorted 
 to a very ingenious procedure. The substance under study was 
 placed in a glass tube which was then closed at both ends. The 
 tube was inserted beneath the skin of the animal and was broken 
 when the small wound had cicatrized. By this method, the employ- 
 ment of a mixture of croton oil and olive oil produced pus in the 
 rabbit without any micro-organisms. 
 
 We owe one of the best works on this subject to Grawitz and Bary. 
 These authors demonstrated that it is hardly possible to produce in 
 rabbits and guinea-pigs suppuration without microbes. The case is 
 different with the dog. A 5 per cent, solution of silver nitrate and 
 concentrated ammonia were found capable of giving rise to aseptic 
 abscess. Terebinthine is, however, the substance endowed with the 
 most marked pyogenic properties. Nathan failed to prove this action 
 owing to the insufficient amount (0.6 c.cm.) employed by him. 
 
 As has well been remarked by Rosenbach, the fundamental short- 
 coming of the first experimenters is the generalization of the results 
 obtained with one animal species. Various substances, particularly 
 mercury and terebinthine, are pyogenie for the dog, while they are 
 only phlogogenic for the rabbit and the guinea-pig. Other experi- 
 menters subsequently confirmed this distinction. 
 
 The problem may now be held to have been solved. In the absence 
 of microbic intervention, suppurations may develop by the action 
 of chemical substances. The list of such substances has been con- 
 
SUPPURATION. 203 
 
 siderably augmented by the latesl contributions upon thu Bubject. 
 The higher the dose and the greater the concentration of these bud- 
 stances, the more energetic is their action. Hence, the possibility 
 of varying their effects so as to obtain s simple sero anguinolenl 
 exudate, an abscess, :i phlegmon, or & slough. 
 
 Researches have further demonstrated thai the character of pue 
 -of chemical origin is the same as thai of pus of bacterial origin. 1 
 
 Lastly, Poliakoff has discovered the very interesting facl thai the 
 more slowly the pyogenic chemical Bubstances are introduced into 
 the tissues, the better they act. T<> demonstrate this, he introduced 
 small capsules of collodion containing five drop- of turpentine oil 
 beneath the skin of a rabbit. A large abscess was produced, although 
 only a part of the amount introduced had had time to diffuse. The 
 counterexperiment consisted in injecting five drop.- a1 once. The 
 result was slight tumefaction without suppuration. 
 
 Pyogenic Properties of Microbic Products. Researches pursued 
 by a number of authorities have demonstrated thai subcutaneous 
 inoculation of sterilized cultures of bacteria may give rise to suppu- 
 ration. This action is in part due to bacterial protoplasm and in 
 part to soluble substances. 
 
 A great number of experiments have shown the presence of pyo- 
 genic material among the secretory products of the staphylococcus 
 •aureus. Leber has succeeded in extracting from its cultures a crys- 
 tallizable body, soluble in alcohol, and possessing inflammatory and 
 necrosing power in the highest degree. The author designates it urn ler 
 the name ■phlogosin and distinguishes it from the non-toxic alkaloids 
 found by Brieger in pus. No analytical study has been undertaken 
 related to substances in cultures of other pyogenic microbes. 
 
 The Non-microbic Suppurations in Clinical Observations. It was 
 for some time believed that the study of non-microbic suppurations 
 was only of theoretical interest. It is at present known that non- 
 microbic suppurations may also occur in man. The pus in chronic 
 salpingites often contains no bacteria. The same is true as regards 
 hepatic abscesses, as has been pointed out by Kartulis, Laveran. 
 Netter, and Peyrot. Since these first contributions thiriy-eight 
 observations have been published concerning non-microbic suppura- 
 tions of the liver. 2 Brouardel and Josue have reported the observa- 
 
 1 Poliakoff. Ueber Eiterung mit und olme Mikroorganismen Centralb. f. Bakt., 
 Bd. xviii. p. 33, 1S95. 
 
 2 Longuet. La sterilite dans le pus des a bees du foie. La Presse rued.. 1S95. p. 99. 
 
204 INFECTIOUS DISEASES. 
 
 tion of a cerebral abscess in which the pus was tree from microbes. 
 Tuffier, operating upon a caleulopyelonephritis, found a litre of fetid 
 pus containing no bacteria cultivable by the ordinary procedures. 
 In the majority of instances in which suppuration is sterile, the puru- 
 lent focus gives rise to no notable disturbance and arouses no general 
 reaction. 
 
 Several hypotheses have been advanced to explain the aseptic 
 character of certain purulent foci. Only one seems to the author 
 acceptable. The probabilities are, to say the least, that the focus 
 has primarily been fertile — viz., that it developed under the influence 
 of the ordinary pyogenic germs, which subsequently disappeared. 
 This view is supported by certain clinical and experimental facts. 
 The author has reported two such experiments pursued with Dr. 
 Josue. Half a cubic centimetre of a culture of proteus vulgaris was 
 injected into the cellular tissue of the thigh of a rabbit. A month 
 later the animal was killed. The necropsj^ revealed a circumscribed 
 abscess the size of an almond. The pus of this abscess contained 
 no microbes visible under the microscope. It produced no growth in 
 the various artificial culture media. Inoculated into the cellular 
 tissue of a rabbit, it caused no lesion. The second experiment was 
 made upon a rabbit with B. coli with analogous results. 
 
 It may be concluded, therefore, that when a suppuration is pro- 
 duced in an animal in such a manner as to allow no communication 
 with the external air, the microbes introduced become gradually 
 attenuated, are no longer cultivable, and can no longer overcome the 
 resistance opposed to them by the living organism. Diminution and 
 disappearance of virulence, diminution and disappearance of vege- 
 t ability, degeneration and dissolution are the successive phases 
 through which pyogenic microbes pass in a closed focus. 
 
 Physical and Chemical Characters of Pus. The characters of pus 
 vary notably from one sample to another. Phlegmonous pus, which 
 is always taken as typical, is an opaque, creamy, yellowish-white, 
 odorless fluid. On ebullition, it smells like milk. Its taste is rather 
 sweet, which is due to the presence of a great amount of soap masking 
 the salty flavor of sodium chloride. 
 
 Under certain circumstances pus occurs as a thick mass, resem- 
 bling certain soft cheeses. Such caseous pus is frequent in animals, 
 particularly in small rodents, such as rabbits and guinea-pigs, em- 
 ployed in laboratories. In other cases, pus is thin. The serous 
 portion is partially separated from the solid elements which are found 
 
SUPPURATION. 205 
 
 in the form of coagula. It Is often contaminated with produd 
 putrid fermentations. H then becomes aniou . gangreno 
 chocolate-brown color, and contain* detritu of necrotic I 
 times gas, and exhales a nauseating odor. 
 
 Rosenbach supposed thai the color of pui was related to the nature 
 of the pyogenic agenl thai the staphylococcus aureus was con- 
 cerned in the formation of yellow pus, and thai the S. albu 
 found in the while variety. This idea does nol seem to be correct, 
 and we need nol wonder, since the S. aureus produces no pigment 
 when it is protected from air, as is the ease with foci of suppuration. 
 
 It is not practicable, therefore, to determine, by examining a 
 sample of pus, whal pyogenic agenl is concerned, or to tell whether 
 the pus is actually inhabited by living microbes or is free from bac- 
 teria. Cultures are indispensable. An except ion may be made only 
 with suppurations caused by the pneumococcus. These are remark- 
 able for their thickness, due to the great amount of fibrin present, 
 and for their greenish color. Hence, the possibility to declare their 
 origin at first sight. 
 
 Microscopic examination may reveal the origin of a suppuration 
 by the various elements present, such as glandular cells, fibres of 
 connective or elastic tissue, crystals of fatty acids, cholesterin, hema- 
 toidin, calcareous grains, and, finally, microbes. 
 
 Certain pathological secretions resemble pus. Such, especially, i- 
 the concrete mucus found in endometritis; then the steatomatous 
 fluid of sebaceous cysts and, to a certain extent, the contents of 
 syphilitic gummata. Error in these cases may easily be avoided. 
 However, the chyliform exudates of serous membranes, notably in 
 the pleura, peritoneum, ami tunica vaginalis, have long been mis- 
 taken for pus. These are probably cases of old purulent foci in 
 which the morphological elements, microbes, and animal cells have 
 undergone fatty degeneration. There remains only an emulsion of 
 fat, the nature of which may readily be determined by microscopic 
 examination or chemical analysis. . 
 
 In genuine pus the microscope reveals the presence of characteristic 
 cells, formerly designated as pyocytes. It is at present possible to 
 differentiate the cells and. in fact, the same elements are found in 
 pus as in the blood. Tus contains poly nuclear neutrophile, eosino- 
 phile, and, exceptionally, basophile leucocytes, as well as mononu- 
 clears and lymphocytes. Finally, there are found two orders 
 degenerated cells: the so-called corpuscles of Gluge, which seem to 
 
206 INFECTIO US DISEASES. 
 
 be made up of an agglomeration of disintegrated cells, having under- 
 gone fatty degeneration, and, in the next place, large spheroidal 
 cells, often in a state of mucoid degeneration, and derived from the 
 fixed cells of connective tissue and from endothelial or adipose cells. 
 
 These various cellular elements are found in variable proportions. 
 The polynuclear neutrophiles predominate in ordinary pus. Gonor- 
 rheal pus is said to be remarkable for the great abundance of eosin- 
 ophiles it contains. In reality, however, these cells abound only at 
 the time when the acute phenomena are subsiding. Their appear- 
 ance is always an indication of recovery. It may be hoped that 
 further advances in the cytological study of pus will furnish data 
 utilizable in clinical observation. Not that the cellular formula} vary 
 with each species of microbe ; on the contrary, they seem to be related 
 rather to certain groups of pathogenic agents. Thus the pus pro- 
 duced by microbes so closely related as are those of variola, varicella, 
 and vaccinia, possesses the same character. In all three instances it 
 is remarkable for the abundance of mononuclears it contains. 
 
 Chemical Characters of Pus. From what has been said regarding 
 varieties of suppuration, it is natural to conclude that pus does not 
 always possess the same chemical characters. The results obtained 
 by analyses cannot, therefore, have a general bearing. They never- 
 theless deserve to be examined in detail. 
 
 Pus is a neutral fluid, at times alkaline, seldom acid. Acidity, 
 when present, is clue to fatty acids and notably to butyric acid. 
 
 Treated with nitric acid, pus gives an abundant precipitate of 
 albumin. The addition of ammonia transforms it into a semisolid, 
 translucent mass, similar to thick mucus. This effect is referable 
 to the action exercised upon the albumin by the leucocytes destroyed 
 bjr the alkali. 
 
 The specific gravity of pus varies from 1020 to 1040. With 
 phlegmonous pus it varies between 1031 and 1033. When left to 
 itself, pus does not coagulate, because it contains no fibrin. AVhen 
 heated, it solidifies at about 167 F. (75 C). Allowed to stand, pus 
 separates into two layers: a clear, superficial layer, the pus serum, 
 and a lower opaque layer, which contains the cellular elements, the 
 pyocytes. There are 710 to 831 parts of serum to 166 to 290 parts 
 of corpuscles. These figures are variable. 1 The chemical analysis of 
 pus corpuscles, made by Hoppe-Seyler, gives the following figures: 
 
 1 Ch. Robin. Lecons sur les humeurs normales et morbides du corps de l'liomme . 
 Paris, 1874, 2d ed., p. 376. 
 
SUPPURATION. 
 
 207 
 
 Organic Substances Oontainto in Owb Hi «>bbd Pabti 01 Dm Cbm*. 
 
 i II 
 
 Proteids l3 » 7fl ' I 
 
 Nuclein 
 
 [llHolllMc ::nli .l.'ilirc:; 
 
 Lccilin 
 
 Fat 
 
 Cholesterin 
 
 Cerebrin 
 
 Exl paotive substanceB 
 
 34,207 [-68,588 67,389 
 
 r i 7.584 
 
 , ' ' ( 7..V,, 
 
 7,400 7,28:', 
 
 5,199 
 4,433 
 
 LO,28 i 
 
 Inorganic Substances Contains. [N Onb Htwdbbd Pasts of D I 
 
 N.,0. . . • 
 
 Ca 3 (Ph0 4 ) 2 . 
 
 Mg 3 (Ph0 4 ), 
 Fe 2 (Ph0 4 ) 2 
 Ph0 4 . 
 
 Na 
 K 
 
 0.205 
 0.113 
 0.106 
 0.918 
 0.068 
 i races 
 
 The pus scrum resembles blood serum in its chemical constitution. 
 Some authorities have even gone so far as to regard the two fluid* 
 as identical. It has been objected that the composition of pus serum 
 is not constant, but the blood serum is no less variable. This is 
 clearly demonstrated by the following figures : 
 
 Serum of Blood 
 (C. Schmidt). 
 
 Serum of Pus 
 
 (Hoppe-Seyler) . 
 
 Water . 
 
 Organic substances 
 
 Inorganic substances 
 
 I. 
 917.15 
 74.43 
 8.42 
 
 II. 
 
 908.84 
 
 82.59 
 
 8.57 
 
 I. 
 913.70 
 78.57 
 7.73 
 
 II. 
 
 905.65 
 
 86.58 
 
 7.77 
 
 Among the substances found in pus serum the most important 
 are undoubtedly the albuminoids, serin, globulin, albumose, and. in 
 osseous abscesses, chondrin. Much stress has recently been laid upon 
 the presence of ferments, toxalbumins, and ptomains, depending in 
 part upon the multiplication of microbes. Dr. Achalme. who has 
 made an admirable study of ferments contained in pus. notes the 
 presence of lipase, amylase, trypsin, casease, a zymase liquefying 
 gelatin, another decomposing peroxide of hydrogen, ami. finally, oxi- 
 dase. The last-named ferment is always very abundant. Sucrase 
 inulase, emulsin, lactase, and plasmase are always absent. These 
 various ferments are not produced by microbes, since they are also 
 found in aseptic abscesses. Dr. Achalme is inclined to assign their 
 origin in the leucoevtes. 
 
208 IXFECTIO US DISEASES. 
 
 Development and Evolution of Purulent Foci. 
 
 Suppuration cannot, in the author's opinion, be held to be a reac- 
 tion aroused directly by chemical or animate pyogenic agents. The 
 mechanism is more complex, and involves two distinct acts. The 
 pyogenic agents first give rise to a necrosis, a primary mortification 
 of tissues. The parts thus altered become a cause of secondary irri- 
 tation which is expressed by the production of round cells, of which 
 some originate on the spot and others migrate from the vessels. 
 
 When pyogenic toxins or a chemical substance, like turpentine, are 
 introduced into the subcutaneous cellular tissue, the first act of 
 pyogenesis is, as has been shown by Bardenheuer with turpentine, 
 a cellular necrosis. A reaction then becomes manifest. This is the 
 second act of the process. Around the necrosed region the cells swell 
 and proliferate. At the same time the vessels dilate and exude a 
 serosity, while the leucocytes migrate from the blood current and 
 take up a position between the necrosed and the inflamed parts. 
 Some of the new cells, however, die and remain in the central zone 
 of the focus. We may admit, then, with Lemiere, that, as a rule, 
 every suppurative focus consists of three zones: a central necrosed 
 zone: a middle zone, characterized by an infiltration of leucocytes, 
 and a peripheral zone made up of fixed cells which proliferate and 
 tend to encyst the lesions. 
 
 Among these phenomena the arrival of leucocytes is a most inter- 
 esting one. It is known that the blood normally contains about 
 6000 leucocytes per cubic millimetre, or 30,000,000,000 for the five 
 kilograms of blood of the human body. In phlegmonous pus 
 125,000 pyocytes per cubic millimetre are counted, or 125,000,000,000 
 per kilogram (one litre). In some cases suppuration amounts to 
 500 or even 1000 c.cm. in twenty-four hours. Taking the lesser 
 figure, 500 c.cm., we see that the focus discharges 60,000,000,000 
 round cells, the greater part of which is represented by leucocytes. 
 This is nearly twice as much as the number of leucocytes contained 
 in the total amount of blood. It is to be noted that the phenomena 
 of diapedesis are prepared and preceded by an increased leucocytosis. 
 The blood of an individual suffering from suppuration is found to 
 contain 15,000 to 20,000 leucocytes per cubic millimetre; in some 
 cases this figure reaches 36,000. 
 
 It now remains for us to learn how this increased production of 
 white corpuscles is effected. It probably depends upon the microbic 
 
SUPPURATION. 209 
 
 and cellular secretions occurring in the focus of suppuration. In 
 fact, it has been established thai the secretions of certain microbes 
 :iii(l the proteins contained in their protoplasm excite leuc 
 (Buchner), In non-niicrobic suppurations this rdle of excitanl musl 
 devolve on the products of cellular destruction. 
 
 The microbic or cellular products thus originating in the affected 
 parts act probably upon the organs in which the leucocytes are 
 formed — the bone-marrow, lymphatic glands, spleen, and, in children, 
 the thymus. They induce proliferation in distanl parte ae they do 
 in the main focus. Nutritive and proliferative overactivity may, 
 perhaps, account in pari for the fever of suppuration. 
 
 Cohnheim had already noted thai the leucocytes could not emi- 
 grate unless the vessels were dilated and the circulation slowed. 
 After these white corpuscles have passed out of the bloodves 
 they make their way to the pyogenic agents. In fact, it has been 
 demonstrated that sterilized cultures of the staphylococcus aureus 
 possess the property of attracting the migrating cells. If a number 
 of capillary tubes be introduced into the abdomen of a frog, some 
 of the tubes being filled with sterilized cultures of the microbe men- 
 tioned and others with water or bouillon, the latter remain un- 
 touched, while the former become filled with numberless leucocytes. 
 The products of organic disassimilation exercise an analogous influ- 
 ence and, consequently, the cells altered by pyogenic substances 
 become a new source of attraction for the leucocytes. 
 
 Some of these leucocytes, when in contact with the accumulated 
 products in the foci, undergo rapid necrosis. Others, simply irritated, 
 proliferate by direct division of the nucleus. "While the migrated 
 leucocytes are at work the fixed cells of the tissue do not remain 
 inactive. The old experiments of Hoffmann and von Recklinghausen 
 tend to prove this. These authors irritated the cornea of an animal 
 and then placed the eye or the entire head in a damp chamber. 
 After some time they found an accumulation of round cells at the 
 irritated point. Yon Recklinghausen has likewise seen the cells of 
 the cornea undergo a change in form and become migrating cells. 
 Similar modifications have been described in the cells of connective 
 and adipose tissue, and in those of serous membranes (Cornil and 
 Toupet). According to Grawitz, connective tissue cells are the seat 
 of an active karyokinesis and are transformed into mononuclear and 
 even polynuclear corpuscles. Let us also recall the recent researches 
 of Ranvier on the clasmatocytes, those large connective tissue cells 
 
 14 
 
210 IXFECTIO US DISEA SES. 
 
 which represent fixed leucocjiies and, under the influence of inflam- 
 mation, are again converted into white corpuscles. 
 
 The respective roles of fixed and wandering cells have been shown 
 by The researches pursued by Ribbert with the staphylococcus, and 
 by Kiener and Duclert with the tetragenus. 
 
 A focus of necrosis is first produced, then large leucocj^tes enter 
 the field, which process takes place coincidently with a proliferation 
 of fixed cells. These various cells are endowed with great phagocytic 
 activity. Such are the phenomena observed on the first dajr. On 
 the second day the fixed cells become the seat of karyokinesis and 
 begin the process of repair. At this time leucocytes of the smaller 
 variety arrive. If, however, the quantity of microbes introduced is 
 quite considerable, many phagocytes die, and some of them, as well 
 as the microbes yet at large, are seized and ingested by the macro- 
 phages — i. e., by the large mononuclear cells derived from the con- 
 nective tissue cells. The phagocj^tic role of fixed cells is especially 
 marked from the fourth day onward. At this period the enveloping 
 or pyogenic membrane becomes vascularized, granulations develop 
 rich in giant cells, which continue the work of phagocytosis, and in 
 white cells, which become the future clasmatocytes. 
 
 According to Ribbert, the round cells defend the organism not only 
 by ingesting the microbes, but by forming a barrier around the 
 virulent focus and establishing a sort of vital competition with the 
 pathogenic agents. The latter succumb because their supply of 
 nutrient elements and oxygen is cut off and they are poisoned by 
 their own noxious substances. 
 
 Thus, while on the one hand the microbes are ingested and de- 
 stroyed, on the other the cells die. If the dead cells are not very 
 numerous, the macrophages pick them up and remove them as well 
 as the bacteria contained in them (scavengers). No suppuration is 
 produced and, after a certain time, the lesion is completely healed. 
 If, on the contrary, the number of dead cells is considerable, the 
 cadavers accumulate in the focus, and thus is constituted the puru- 
 lent collection. 
 
 In most cases the abscess opens externally, and the dead elements 
 with a great number of microbes are thus expelled. Nevertheless, 
 virulent agents remain in the focus, and it ma}^ be asked how a cure 
 is ever possible, especially when the purulent focus becomes encysted. 
 In such cases, the author believes a chemical modification of the 
 fluids and tissues of the organism takes place, rendering the media 
 
SUPPURATION. i\\ 
 
 unfavorable for the developmenl of the microbe . The vitality of 
 the latter gradually declines, and their removal by phagocyte i 
 easily accomplished. II' the focu remains closed, cure i po 3ible, 
 but the pus then undergoes tran formation . [n some instances the 
 elements of which it is composed undergo fal ty degeneration, -<< thai 
 the focus is transformed into a chyliform fluid. In other cases, the 
 scrum is absorbed and I here remain a ca eou mass which may later 
 become infiltrated with calcareous suits. 
 
 The suppurative process is attended by local and general symp- 
 toms. The local symptoms are well known as the four cardinal signs 
 of inllaniniaiion— swelling, pain, heat, and redness (tumor, dolor, 
 color et ruber). The primary phenomenon is tumefaction, due to 
 nutritive and vascular modifications which attend and explain the 
 pyogenesis. 
 
 Pain, which is often the first appreciable phenomenon, is due to 
 increased sensitiveness of the parts by the excessive influx of blood; 
 to irritation or rupture of nerve filaments, and, finally, to compres- 
 sion of neighboring parts. 
 
 Heat and redness are two symptoms which have been described 
 according to the evolution of superficial suppurations and which are 
 attributed to an exaggerated afflux of blood, augmentation of nutri- 
 tive exchange, and proliferation of cells. No experiments, however, 
 have as yet been made to verify whether suppuration in deep-seared 
 organs is also attended with a local rise of temperature. 
 
 When undisturbed, an abscess tends to open either into a neigh- 
 boring organ or outwardly. When opened, whether naturally or sur- 
 gically, the pus and the pyogenic microbes pass out of the focus, and 
 this is folloAved by alleviation of the local and general symptoms. 
 In some cases evacuation is accomplished at once, and cicatrization 
 is soon established. More often, however, the pus re-forms and the 
 process lasts for a more or less prolonged period. 
 
 The local manifestations are in most cases accompanied by general 
 phenomena. When the latter appear in the beginning of the pre- - - 
 a grave infection is to be feared, since they indicate a special viru- 
 lence of the pathogenic agent. 
 
 We do not need to dwell here upon the various disturbances which 
 may be observed. They are those common to all infectious pro- 
 cesses. The onset is characterized by chills : a rise of temperature 
 then occurs: the fever may be continuous or remittent, or even 
 frankly intermittent. At a more advanced stage it may assume a 
 
212 IXFECTIO US DISEASES. 
 
 hectic character, accompanied by secretory modifications, albumin- 
 uria, etc., which will be referred to again. 
 
 Cold Suppurations. From the point of view of their evolution, 
 abscesses have been divided into two classes: hot abscesses, with an 
 acute and clearly inflammatory evolution, and cold abscesses, char- 
 acterized by a slow and indolent progress. The latter are often due 
 to the tubercle bacillus. It was at one time assumed that they were 
 always dependent upon the pathogenic agent named. Recent con- 
 tributions demonstrate, however, that cold abscesses, whether cuta- 
 neous or osseous, are not necessarily of tuberculous nature. The 
 author observed a case of cutaneous cold abscess clue to a common 
 pus coccus, the staphylococcus aureus. 1 Facts of this kind are not 
 rare. Hallopeau 2 has reported two interesting cases, and Hulot, 3 in 
 an interesting thesis, has described cutaneous suppurations which 
 evolve like tubercular lesions and are attended by a progressive 
 cachexia ending in death. These cold streptococcic abscesses are 
 especially frequent in children, although they may also be observed 
 in adults. A similar evolution may also be observed in cases of 
 osteomyelitis. 
 
 In most instances, however, cold suppurations of the bones are clue 
 to Eberth's bacillus. We find in the memoire of Chantemesse and 
 Widal a great number of observations proving the slow and insidious 
 course of certain osteomyelites of typhoid origin. 
 
 Suppuration in the Various Parts of the Organism. 
 
 All parts of the organism are not equally liable to invasion by 
 pyogenic microbes. Suppuration is rare in cartilages, owing, perhaps, 
 to their scanty vascularization. There are, however, inexplicable 
 differences between analogous tissues. Thus, while abscesses are 
 quite frequent in the brain, the spinal cord is very seldom, if ever, 
 the seat of a purulent focus. The same is true with reference to 
 muscular tissue. There are but three muscles which are at times 
 invaded by suppuration, namely, the iliac psoas, the sternocleido- 
 mastoid, and the deltoid. The resistance of the lungs is also very 
 remarkable. In spite of the frequency of infections and the great 
 number of pyogenic germs entering the respiratory tract, pulmonary 
 
 1 Roger. Abces froids dus au staphylocoque dore. Gazette hebdomadaire, August 
 6, 1892. 
 
 2 Hallopeau. Abces cutanes et sous-cutanes multiples et recidivants chez les jeunes 
 enfants. Annales de dermatologie, 1894. 
 
 3 Hulot. Infection d'origine cutanee chez les enfants. These de Paris, 1895. 
 
SUPPURATION. 213 
 
 suppurations are quite limited and special. No more than small 
 purulent points are observed in bronchopneumonia foci; the pr< 
 is suppuration in the cavities. True pulmonary absce i ol 
 rare occurrence. 
 
 Whatever the suppurating organ or tissue under observation may 
 be, the same pyogenic agents are always discovered. Aside from the 
 specific suppurations, the microbes Pound in pus are generally the 
 staphylococcus or the streptococcus, the colon bacillus, the pneumo- 
 coccus, and less frequently the tel ragenus or various species of minor 
 importance. It is to be remembered, however, thai the rel 
 frequency with which these pyogenic species are mel with varies 
 considerably according to the part affected, ft is readily cona 
 thai the bacteriological nature of a suppuration oiusl be related to 
 the species normally inhabiting the region invaded. 
 
 Cutaneous Suppurations. The researches of Remlinger shovi thai 
 there are 40,215 bacteria to the square centimetre of skin. I 
 eight out of fifty colonics are composed of staphylococci. C 
 quently, when a suppuration occurs in the skim this microbe will be 
 found in most cases. 
 
 Buccopharyngeal Suppurations, ft is not the staphylococcus but 
 the streptococcus that is most frequently met with in buccopharyn- 
 geal suppurations, since the latter microbe is constantly present in 
 the mouth. Some other pyogenic species, such as the tetragenus, 
 pnemnococcus, staphylococcus, proteus vulgaris, and colon bacillus 
 are also found, but in small numbers. It is the streptococcus which 
 easily becomes exalted and gives rise to the different varieties of 
 phlegmonous sore throat and abscesses of the tonsils. 
 
 Nasal Suppurations. It is admitted that the staphylococcus is 
 the microbe concerned in most cases of purulent rhinitis. There is 
 no doubt that this coccus does produce nasal suppurations. The 
 author has found it in abscesses of the septum in a state of purity. 
 It is well to remark that the mucopus flowing from the nares before 
 the abscess was opened contained no microbes other than the staphy- 
 lococcus. 
 
 It is important to call attention to the frequency and gravity of 
 purulent coryza of streptococcic origin in scarlatina. 1 It is an early 
 manifestation characterized by a continuous discharge and often 
 accompanied with enormous cervical adenopathies and suppurative 
 
 1 Chausserie-Lapree. De la rhinite purulente clans la scarlatine These de Paris. 1900. 
 
214 IXFECTIO US DISEASES. 
 
 otitis. The microscopic examination reveals the streptococcus 
 almost in a state of purity. The streptococcus was found associated 
 with the staphylococcus aureus in one case. This impure culture 
 inoculated into a guinea-pig caused death of this animal in forty- 
 eight hours. 
 
 Auricular and Ocular Suppurations. Otitis media may be due to 
 anaerobic microbes, but in most cases it depends upon the strepto- 
 coccus, pneumococcus, staphylococcus, tetragenus, the bacillus of 
 Friedlaender, and the bacillus proteus. The pneumococcus is par- 
 ticularly frequent in primary otites, the streptococcus in secondary. 
 All may give rise to lesions in more or less distant parts, especially 
 to suppuration of the mastoid cells, phlebitis of the sinuses, abscess 
 of the cerebrum and cerebellum, meningites, and even pyemia. 
 When, however, suppuration has lasted for some time, the microbe 
 or microbes which may have been present in the beginning of the 
 process disappear and the staphylococcus alone is found. Such at 
 least is the fact in odorless suppurations, since pus which becomes 
 fetid contains anaerobic organisms capable of invading the mastoid 
 and giving rise to gangrenous septicemia and to suppurative foci in 
 distant parts. 
 
 Unlike the suppurations of the parts already mentioned, those of 
 the eye seem to be due, in most cases, to specific microbes. Puru- 
 lent conjunctivitis generally depends upon the gonococcus. Other 
 microbes, however, may likewise be concerned, such as the bacillus 
 of Koch-Weeks and the ordinary pyogenics. 
 
 Suppurations of the Respiratory Passages. In the deep parts of 
 the respiratory passages the ordinary pyogenic microbe is the pneu- 
 mococcus, as, for instance, in cases of bronchopneumonia, in which 
 the streptococcus, the pneumobacillus, and the staphylococcus may 
 also be found, but less frequently. 
 
 In cases of fibrinous pneumonia suppuration is exceptional. When 
 it occurs it is due to a secondary infection with the staphylococcus 
 aureus, seldom with the streptococcus or pneumobacillus. Contrary 
 to classical opinion, however, it seems to be established that the 
 suppuration of a pneumonic focus may be due to the pneumococcus 
 alone. This is clearly evidenced by the observations of Zenker and 
 especially by the researches of Griffon, who studied five cases of 
 suppurative pneumonia. 
 
 Suppurations of the Digestive Canal. The colon bacillus and the 
 intestinal streptococcus were until recently held to be chiefly respon- 
 
SUPPURATION. 216 
 
 sible for suppurations of the alimentary canal. The anaerobic 
 cies, and notably B. ramosus of Veillon, are al presenl suppo '-'I to 
 play a more important role Concerning this subject we po 
 very few documents. All we know with regard to phlegmonous 
 enteritis is contained in the work of Ziegler and Mint/, who detected 
 the streptococcus. The production of hemorrhoidal phlebitee and 
 anal abscesses is attributed to the colon bacillus. We are better 
 in torn km I as regards appendicitis. Mosl authorities admil the action 
 of the colon bacillus and streptococcus. Veillon argues thai the 
 principal role is played by the B. ramoms, and he think- thai the 
 fetid character of the pus and the gangrenous state of the wall- pi 
 the anaerobic nature of the process. Appendicitis is, therefore, held 
 by many to be a variety of enteritis, its particular character being 
 due simply to the special anatomical conditions of the affected part. 
 
 Experimental Appendicitis. In order to elucidate the mechanism 
 of appendicitis experimentation was resorted to by Roux (of Lau- 
 sanne). As, however, he operated upon the pig — an animal without 
 an appendix — he previously created an appendix at the expens 
 the cecum, and obtained negative results. Taking up the question 
 with Dr. Josue, 1 we operated upon the rabbit. The appendix of this 
 animal differs from that in man in that it is far more voluminous 
 and is in free communication with the cecum, but its analog}' with 
 the appendix of man is admitted by anatomists, such as Krause, 
 Ribbert, etc. 
 
 Some time after the publication of our researches on experimental 
 appendicitis the question was taken up by Dr. Gervais, who con- 
 firmed our conclusions, and by Beaussenat, who obtained appendi- 
 cites by exciting gastrointestinal disturbances. Dr. Chastanet 2 pur- 
 sued experimental researches in our laboratory and demonstrated 
 that it is possible to induce appendicitis in the rabbit by causing 
 this animal to swallow microbic cultures. The appendix becomes 
 affected the same as the other portions of the digestive canal, but 
 its reparation seems to be less easy. Chastanet further determined 
 this difference by producing traumatism in the various portions of 
 the intestine and noticing that the lesions of the appendix persisted 
 long after cicatrization of the lesions in the other parts. The lesions 
 found in all these experiments were ulcers. These facts lead to the 
 
 1 Roger et Josue. Appendieite experimentale. Society med. des hopitaux, Jan. 31. 
 1S96. Recherches experimentales sur I'appendicite. Revue de inedecine. June. 1 - 
 
 2 Chastanet. Recherches experimentales sur I'appendicite. These de Pari-. 1897 
 
216 
 
 INFECTIOUS DISEASES. 
 
 conclusion that the appendix represents a lymphoid organ, compar- 
 able to the tonsil. Like the latter, it is frequently the seat of acute 
 primary or secondary infections. This is what happens when the 
 intestinal germs become exalted in consequence of some dietetic 
 error, a depressing cause, or an infectious or other disease. The 
 appendicular inflammation may be slight and be completely repaired. 
 In other cases it is expressed by ulcerations, which are less easily 
 
 Fig. 2. 
 
 Experimental appendicitis of eighteen days' standing. 
 
 reparable. The latter may cicatrize or, on the contrary, give rise to 
 adhesions which constrict the cavity and often obliterate it. Primary 
 obliteration of the appendix is hardly conceivable. The idea that 
 its obliteration represents the last stage of an ulcerating process 
 seems to be in perfect harmony with the ensemble of published facts. 
 In our own experiments it was found necessary to inject virulent 
 microbes into the intestinal cavity in order to induce appendicitis. 
 
SUPPURATION. 
 
 217 
 
 
 Aseptic ligation of the appendix Is sufficient. The rabbit* thus 
 operated upon first lose flesh and seem to be Buffering. They 
 recover, however, grow fat, and qo longer presenl any disturbance. 
 Nevertheless, at the end of a few days, palpation of the abdomen 
 reveals the presence of a deep-seated tumor, of 
 greater or less size and consistency, situated to 
 (lie right side of the median line. The majority of 
 the animals thus survive almost indefinitely. They 
 had to bo killed in order to study the course of the 
 lesions. Some rabbits died a few days after the 
 ((Iteration. Those suffered from a profuse diarrhea, 
 and rapidly emaciated. 
 
 The lesions vary, of course, according to the 
 length of time since the operation. The day fol- 
 lowing the operation the walls of the appendix 
 are found to be more vascularized than normally; 
 its cavity is distended by a variable quantity of 
 serosity. The second day the surface of the cavity 
 is covered with a purulent layer. From the fourth, 
 at times even from the third day onward, soft but 
 highly vascularized adhesions are formed. The 
 color of the appendix is milk-white, suggestive 
 of a purulent transformation. The cavity con- 
 tains a greenish substance. On the sixth day the appendix still 
 presents an almost normal aspect, but it is closely adherent to the 
 surrounding intestinal coils. Its contents are mixed with pus and 
 some purulent floating flocculi. 
 
 The entire inside of the appendix then undergoes a purulent trans- 
 formation. Coincident ly, the walls become distended, so that toward 
 the eighth clay an ovoid cyst is found measuring about 3 cm. in 
 diameter. (Fig. 2.) After having reached this degree of develop- 
 ment, the purulent pouch seems to remain stationary, as we were 
 able to convince ourselves by killing one of the animals three months 
 after ligation of the appendix. (Fig. 3.) 
 
 In no case did we observe the pouch open into the peritoneum, 
 but in several it was so thin at certain points that rupture might 
 well occur sooner or later. 
 
 The microscopic examination of the pus reveals the presence of 
 leucocytes and microbes. In old cases, the leucocytes undergo 
 granulofatty degeneration. Bacilli are rare. In some cases it is 
 
 Experimental ap- 
 pendicitis "f three 
 
 months' standing. 
 
218 INFECTIO US DISEASES. 
 
 necessary to resort to cultures to demonstrate the presence of the 
 colon bacillus. 
 
 Histological examination reveals extensive lesions. Fig. 4 rep- 
 resents the state of the walls three days after the operation. When 
 slightly magnified, it is seen that the general structure of the appen- 
 dix is preser\ ed. 
 
 Fig. 4. 
 v.'C h ' N) ••>'-'• •'•'.' '" •'.'■ >"> 
 
 
 
 • ■:. 
 
 Wall of the appendix at the third day after ligation. X 8 diameters. 
 
 If a more advanced case is examined, for instance, one fifteen days 
 old, it is seen that the normal structure of the organ has completely 
 disappeared. (Fig. 5.) When slightly magnified it appears like a 
 compact tissue with irregular contour, presenting here and there foci 
 of necrosis. 
 
 Fig. 5. 
 
 r — -a 5'7 ' r'~ 
 
 iPwv,,.. 
 
 '' "*" 
 
 Wall of the appendix fifteen days after ligation. X 6 diameters. 
 
 With high magnification is seen a fibrillary tissue with numerous 
 nuclei. At certain points there are some foci of necrosis vaguely 
 recalling the form of follicles. Elsewhere are found embryonic 
 masses made up of infectious nodules. The presence of a few mus- 
 cular cells may yet be perceived. It is impossible to detect microbes 
 in the sections. 
 
SUPPURATION. 219 
 
 The importance recently attributed to foreign bodies in the appen- 
 dix led us to make another series of experiments. We introduced 
 into the appendix of two rabbits a ball of wax, of sufficienl size in 
 one of the cases to distend the intestinal walls. No disturbance 
 resulted from the operation. The animals were killed at the end of 
 a fortnight and no lesions were found. The appendix . 
 lutely normal. Moreover, the foreign body could nol be found, as, 
 in spile of its considerable Bize, h had been forced oul by the con- 
 tractions of the appendix. 
 
 Prom our scries of experiments ii is seen thai only one experi- 
 mental procedure produces ulcerative appendicitis, viz.. complete 
 ligation of the appendix. The cul-de-sac musl be transformed into 
 a closed cavity. Even double si rid ure does not cause inflammation, 
 nor does the introduction of a ball of wax. 
 
 It now remains to account for the manner in which the suppuration 
 of the appendix is produced when completely ligated. It is not the 
 result of an arrest of the circulation, since the numerous vessels 
 passing through the peritoneal fold amply suffice to insure the circu- 
 lation. In fact, if, after having ligated the appendix, an appen- 
 dicular fistula be created, by which the free extremity of the 
 is connected with the exterior, no notable incident occurs. As s< 
 however, as the fistula is obliterated and the cul-de-sac is I ransfi >] 
 into a closed cavity, suppuration sets in. This simple experiment 
 demonstrates that suppuration is produced because an arrest of the 
 flow of fluids occurs. ^Ye resorted to another series of experiments 
 "which proved that the suppuration is not due. as some authori- 
 ties suppose, to exaltation of pyogenic germs. Cultures made with 
 a few drops of the contents of a normal appendix proved capabl 
 producing suppurative lesions in rabbits and death in nine day-. 
 while similar cultures prepared two or three days after ligation of 
 the appendix had exactly the same virulence as those made before 
 the operation. After the fourth day the pathogenic power of the 
 intestinal contents declined rapidly. It is a general law, that in 
 purulent foci microbes become progressively weaker, and even finally 
 disappear. The mechanism of appendicular suppuration is the same 
 as that governing the formation of all purulent foci. In fact, it is 
 known that pyogenic microbes act by virtue of the soluble sub- 
 stances which they secrete. Under normal conditions, however, the 
 products of the microbes in the appendix are discharged with 
 the fecal matters. After ligation the toxins accumulate and. as the 
 
220 INFECTIOUS DISEASES. 
 
 experiments of Poliakoff have shown, the products of the pyogenic 
 germs act particularly when they are elaborated slowly and progres- 
 sive^. We are thus led to the conclusion that appendicitis depends 
 upon the general causes of suppuration. It is a tox-infectious lesion. 
 
 Abscesses of the Liver. The portal vein represents the main 
 channel for the introduction of microbes into the liver. As hepatic 
 abscesses are connected with intestinal lesions, it is the portal vein 
 which, owing to its anatomical connections, insures morbid sym- 
 pathy between the alimentary canal and the liver. In some cases 
 germs pass through this vessel without leaving any trace, as is notably 
 the case in dysentery. In other instances a suppurative pylephle- 
 bitis affecting the entire portal system and its contributory branches 
 occurs and represents an intermediate incident accounting for the 
 propagation. 
 
 After dj^sentery, we must also cite, among intestinal affections 
 which give rise to hepatic suppurations, all those which are respon- 
 sible for intestinal ulcerations: typhoid fever, tuberculous enteritis, 
 tyj ihlitis, and appendicitis. It is to be noted, however, that abscesses 
 are as rare under these conditions as they are frequent in dysentery. 
 
 The most varied pyogenic microbes may be encountered in hepatic 
 suppurations. The streptococcus as well as the colon bacillus and 
 the staphylococcus are found. Dr. Lannois has reported an inter- 
 esting observation of an hepatic abscess with Eberth's bacillus 
 occurring in the course of a typhoid fever and caused by a pyle- 
 phlebitis. 
 
 A point of interest in the history of hepatic abscesses is the fact 
 that the pus is often sterile. This has been clearly ascertained in 
 forty observations. As has already been remarked, every old sup- 
 purative focus finally becomes sterile, but some hepatic abscesses, 
 by no means old, have been found equally free from microbes. The 
 explanation is found in the well-known destructive action of the liver 
 upon bacteria. 
 
 Dysenteric abscesses of the liver are seldom sterile. Out of thir- 
 teen cultures made by Kartulis, microbes developed in five instances. 
 The staphylococci aureus and albus, and the B. proteus vulgaris 
 were the species found under these conditions. On the other 
 hand, examination of sections demonstrated that the walls of the 
 abscesses contained bacteria, even when the cultures were negative. 
 Such was the result in ten cases. There remain, therefore, but three 
 observations of sterile abscesses. 
 
SUPPURATION. 221 
 
 Whether bacteria are detected or aot, Kartulis always found 
 amebaD. Some experimenl pursued by Marchoux upon cat* show 
 that dysenteric abscesses of the liver ma) re all from the injection 
 of dysenteric stools containing amebse. 
 
 Suppurations of the Pancreas. Although placed anatomically in 
 a sufficiently analogous situation, the pancrea i far less frequently 
 affected than the liver. Like the latter organ, it is infected either 
 by germs carried to it by the bloodvessels or by bacteria entering 
 it by way of the excretory channels. The conditions favoring infec- 
 tion are evidently the same in both in tances. Pancreatic suppu- 
 rations may, then, be observed in puruleul infections, in variola, 
 appendicitis and in consequence of lesion of the stomach and duo- 
 denum. The colon bacillus is the microbe found in the majority 
 of cases, and it seems thai the localization of this microbe i- 
 favored by the previous lesions of the organs — cyst.-, sclerosis, 
 lithiasis. 
 
 Suppurations of the Urinary and Genital Organs. Like the diges- 
 tive apparatus, the genito-urinary tract communicates by its ter- 
 minal end with the external world. It may, therefore, be infected 
 from without as well as from within. In man, however, protection 
 against the outward germs is fairly well insured. Under normal 
 conditions, microbes do not penetrate beyond the fossa navicularis. 
 Nevertheless, bacteria are not infrequently found in the urethra of 
 men otherwise healthy, notably the streptococcus giganteus urethras. 
 The bladder offers great resistance to microbic invasion. It is quite 
 difficult to infect it when healthy. This is no longer true, however, 
 when it is the seat of a lesion or when some obstacle opposes the 
 free discharge of the urine. Upon a soil thus prepared the most 
 varied pathogenic agents develop abundantly, inducing suppuration 
 of the bladder, ureters, pelvis, and kidneys. They may even go 
 farther and give rise to perinephritic phlegmons. 
 
 The gonococcus, which is to-day held to possess greater migratory 
 powers than was formerly believed, represents in women an impor- 
 tant cause of salpingitis. According to the researches of E. Reymond, 
 it vegetates upon the surface of the mucous membrane in the desqua- 
 mated epithelial cells and but exceptionally invades the walls of the 
 Fallopian tubes. In streptococcic salpingitis, on the contrary, the 
 microbe strongly tends to propagate toward the peritoneum. Finally. 
 the salpingites due to the colon bacillus are observed in those c - - 
 in which adhesions are formed between the intestine and the Fallo- 
 
222 ISEECTIOUS DISEASES. 
 
 pian tubes. This fact leads to the opinion that the colon bacillus 
 is derived from the intestine. 
 
 Suppurations of the Nerve Centres. The other parts of the organ- 
 ism not communicating with the exterior cannot be attacked by 
 pyogenic microbes, except as a result of traumatism, which allows 
 them in penetrate directly, or of extension of a neighboring lesion, 
 or of a general infection ending in localizations. The relative fre- 
 quency of the microbic species found under these conditions will at 
 times depend upon the situation of the part affected. Abscesses of 
 the cerebrum and cerebellum being in most cases consecutive to 
 otitis, the microbes found are those concerned in suppurations of the 
 middle ear. 
 
 Suppurations of the Serous Membranes. Serous membranes are 
 generally invaded by contiguity, as a result of a purulent focus devel- 
 oping in subjacent organs. Such, however, is not always the case. 
 Localization may first occur in the nervous system, as is the case 
 with articulations. The same is true with regard to the meninges, 
 pleura, and peritoneum. 
 
 In the pleurisy of children the pneumococcus is the microbe com- 
 monly found. The streptococcus is comparatively seldom met with. 
 In adults, on the contrary, the streptococcus is more frequently 
 found than the pneumococcus. Among the other pyogenic microbes, 
 we m r dy cite the staphylococcus, the bacillus of Friedlaender, the 
 typhoid bacillus, and the colon bacillus. These findings are not 
 merely of theoretical interest. It is known that recovery from puru- 
 lent pleurisy is very frequent in cases in which the pneumococcus is 
 the pathogenic agent. The differential diagnosis may be at least 
 suspected, if not established, by simply taking into account the 
 course of events and especially the characters of the fluid. In the 
 majority of cases the pus of pneumococcic pleurisies is thick, viscous, 
 and greenish. That of streptococcic pleurisies contains a greater 
 proportion of serum and gives a grayish deposit. Certainty is, of 
 course, to be reached only by bacteriological research. In this con- 
 nection it may be stated that a purulent pleurisy, the fluid of which 
 is free from bacteria, must be considered tuberculous in nature 
 (Fraenkel). 
 
 The principal cause of peritonitis being in the intestines, it is 
 readily conceived that peritonitis due to the colon bacillus must be 
 quite frequent. The intervention of the colon bacillus also accounts 
 for typhoidal peritonites. This is not invariably the case, however. 
 
SUPPURATION. 223 
 
 Fraenkel has reported a case in which the exudate ol a peritonitis 
 occurring in the course of a typhoid fever contained no other microbe 
 than the typhoid bacillus. When infection of the peritoneum occurs 
 through the genital organs, as is the ca e e pecially in women, the 
 gonococcus is sometimes found, bu1 tnore frequently the strepto- 
 coccus. 
 
 In most cases of purulenl pericarditis the inflammation depends 
 upon a genera] infection, bul it may occur independently or accom- 
 pany oilier purulent lesions affecting the viscera or serous mem- 
 branes. That is to say, purulenl pericarditis is seldom primary. I' 
 represents the localization of an infect ion the starting point of which 
 escaped observation. Suppurative pericarditis sometimes occui 
 a result of affection of the respiratory apparatus — i. c, pneumonia, 
 bronchopneumonia, even dilatation of the bronchi, and, in these 
 instances, it is due to the pneuinococcus. It is sometimes consecu- 
 tive to an eruptive fever: measles, varicella, and. above all, scarla- 
 tina and smallpox. It is, however, a complication of far rarer occur- 
 rence than was formerly believed. My own statistics, inclui ling 531 1 1 
 cases of eruptive fevers, show but two cases of purulent p< ricarditis. 
 
 The pneuinococcus and streptococcus are the two microbes mosi 
 frequently concerned in purulent meningitis. Among the bacteria 
 of uncommon occurrence we may cite the staphylococcus aureus, the 
 typhoid and colon bacilli, and the bacillus of influenza. AVe do not 
 include the lneningites of specific nature, caused by Koch's bacillus, 
 and the epidemic cerebrospinal meningitis which depends upon a 
 particular microbe — the meningococcus of "Weichselbaum (diplococ- 
 cus intracellularis), formerly confounded with the pneuinococcus. 
 
 Meningitis is not frequent in eruptive fevers. I have met with 
 but one case. An otitis, developing in a man convalescing from 
 measles, became the starting point of a purulent infection. Numer- 
 ous suppurative foci appeared in the joints, and at the necropsy 
 the meninges were found full of pus. This lesion, in spite of its 
 intensity, had remained absolutely latent. The patient had retained 
 consciousness to the last, and never complained of any suffering in 
 the head. The absence of morbid manifestations is probably to be 
 attributed to the absence of dropsy of the ventricles. The author 
 would like to remark that, at all events, suppurative meningites. 
 even when extensive, occur in a latent manner oftener than is 
 believed. They are expressed by no symptoms whatever. 
 
 If w T e consider the ensemble of the results to which the study of 
 
994 INFECTIOUS DISEASES. 
 
 suppuration leads us, Ave perceive that pus originates when the 
 leucocytes fail in their task of destruction of the invading microbes. 
 Numbers of cells are killed by microbic secretions. Their cadavers 
 constitute the pyocytes — useless cells, true foreign bodies — which 
 must be eliminated. If these are not very numerous, the macro- 
 phages remove them. In most cases, discharge occurs outwardly 
 and suppuration becomes established. Suppuration, then, is the 
 establishment of an exit for the microbes, toxins, and destroyed cells. 
 Suppuration is a common process to which a great number of para- 
 sites may give rise. But all of them act in the same way, viz., by 
 secreting necrotizing substances. Suppuration is reaction against 
 toxins. In order for this reaction to be produced, the organism must 
 possess a certain degree of resisting power. If it is incapable of 
 reacting, two events are possible: first, reaction being insufficient 
 or nil, the pyogenic micro-organisms invade the whole organism; they 
 cease to produce pus, and give rise to septicemia. Second, the necro- 
 tizing action of the toxins is so strong that the tissue cells undergo 
 fermentations analogous to those which characterize putrefaction. 
 AVe then find ourselves confronted by a new process — another ter- 
 mination of inflammation — related to suppuration by numerous 
 transitions. It is this process that we are now about to study, 
 namely, gangrene. 
 
(Ml A PTEE VIII. 
 
 GANGRENE. 
 
 Definition of Gangrene. Onu ch Kavoring the Developmenl "\ Gangrene, [mportanoe 
 of Vascular and Nervous Lesions. Auxiliary Rdle •>( Certain Toxic £ 
 Study of the Principal Agents of Gangrene. Rdle of \iia§robic Microbes. Ii«'«l<- 
 of Facultative Anaerobics. The Agents of Gangrenous Uammitia< The Microbe 
 
 of I'.rnign Gangrene of the Kvelid . i:.,i.- of Pyogenic Microb , Relationship 
 between Suppuration ;i n< I Gangrene. Gangrene in Different Parts of the Organ- 
 ism. Chemical Analysis of Gangrenous Products. 
 
 Gangrene is a morbid process essentially characterized by the 
 
 i no i- tifi cation and putrefaction of (issues. 
 
 There can never be putrefaction without microbes. Gangrene, 
 then, is always of microbic origin, and should be distinguished from 
 aseptic mortifications which are designated as necrobioses. The 
 distinction is not, however, as sharp as may appear at first Bight. 
 There are microbic gangrenes in which mortification is the predom- 
 inant phenomenon, attended by little, if any, putrefaction. These 
 are cases of dry gangrene closely related to simple necrobioses. In 
 a great number of cases experimental and bacteriological investiga- 
 tions have not been sufficiently complete to determine whether the 
 process is due to an infection or merely to cellular disturbance. In 
 cases of toxic gangrene, like ergotism, or trophic gangrene, like ulcer- 
 ating dermosynovitis, it is not known whether the process is due 
 simply to poisons or nervous lesions or to a superadded infection 
 occurring in tissues no longer capable of resisting microbic invasions. 
 The latter view seems to me more rational, but it is not accepted 
 by all, and must be held subject to modification. 
 
 Gangrenes, properly so called — i. e., those of microbic origin — 
 cannot develop except in parts which are in direct or indirect com- 
 munication with the exterior. They are observed in the skin, 
 mucous membranes, and the respiratory apparatus. Tissues or 
 organs not in contact with the air (abdominal viscera, nerve centres) 
 cannot be the seat of gangrene unless a primary focus, whence 
 microbes may penetrate the organism, exists. Suppose, for instance, 
 that the artery of a limb is obliterated, gangrene may appear in the 
 parts deprived of circulation. Such is the case in senile gangrene. 
 
 15 
 
226 IXFECTIOUS DISEASES. 
 
 If, however, the obstruction occurs in a cerebral artery, necrobiosis 
 or softening, but no gangrene, results. 
 
 There is no specific microbe of gangrene. The process is a com- 
 monplace one, and what we said with regard to suppuration can also 
 be applied to it. As in that case, pathogenic agents maybe divided 
 into two groups. Some of them, when in contact with healthy 
 tissues, possess the power to engender the two stages of gangrene — 
 the mortification of living elements and their putrefaction. Others 
 act only upon altered, partly mortified tissues. In the latter instance 
 pyogenic microbes are found in the morbid focus, and they act upon 
 the diseased organism as they do upon lifeless matter. No doubt, 
 the division is not absolute. The development of even the most 
 virulent microbes is materially facilitated by a great number of 
 accessory causes, such as mortification and chemical alterations of 
 tissues and the association of different microbes. These conditions 
 are not indispensable, however, and occupy a secondary place. 
 Their intervention is of prime importance when the invading micro- 
 organisms are of the kind which become capable of giving rise to 
 gangrene only on favorable occasions. 
 
 Among the latter are the pyogenic microbes. This is not sur- 
 prising, since we have shown that in all suppurations two successive 
 acts are to be distinguished: namely, the necrosis of the invaded 
 tissue and the reaction of the organism, resulting in the production 
 of cells which make up the purulent exudate. For the production 
 of the second phenomenon a certain degree of reactionary power is 
 required. If the tissue is altered or the organism profoundly debili- 
 tated, the necrotic process prevails, and gangrene develops. In 
 nearly all instances, however, the organism makes some reactionary 
 effort to eliminate the dead elements, and suppuration appears sec- 
 ondarily around the slough. This result is observed, even when the 
 process is due to the specific agents of gangrene, provided they are 
 attenuated. The septic vibrio, which is the type of this kind of 
 microbes, produces gangrene when very active or when inoculated 
 into susceptible animals, but recedes to the rank of a pyogenic when 
 it is attenuated or when the animals possess a higher degree of 
 resistance. In brief, the pyogenic microbes when exalted become 
 necrogenic; the neurogenic microbes when attenuated become pyo- 
 genic. 
 
 As we have already noted, two stages are observed in gangrene: 
 namely, necrosis and putrefaction. This has led some authorities to. 
 
GANGRENE, ill 
 
 Gonipare or even identify gangrene with the proa oi putrefaction 
 occurring in the cadaver, The analogy should nol be overempha- 
 sized. A dead tissue abandoned to putrefaction do< no1 pr< 
 the same aspect as a gangrenous part, and ye1 the microbes developed 
 maybe identical in both cases, and chemical analy i mi 
 similar transformations in both (issues. The difference lies in the 
 fact Mini, in the production <>!' gangrene, ■■> pari i- played by the 
 living elemenl -%. e., the reactionary process. No one, however, has 
 ms yet attempted to demonstrate the difference . All we can do, 
 therefore, is to offer n few reflections intended to show how, in out 
 opinion, (Ik- experiments should be pursued in thif connection, 
 
 One difference between putrefaction and gangrene musl depend 
 upon arrest or persistence of the circulation, viz., influx of blood 
 serum, lymph, leucocytes, and coloring mailers of the blood. The 
 latter, by being decomposed, musl contribute to the color of gan- 
 grenous tissue. These various conditions, however, do noi suffice to 
 explain all phenomena: Firstly, because the circulation is a1 times 
 interrupted, as in the case of dry gangrene, and yet the pr< 
 retains its special character. Secondly, when we cause putrefaction 
 in a tissue immersed in blood we render the process .more intense, 
 but we do not produce gangrene. We are thus led to the conclusion 
 that gangrene is dependent upon the action of putrefactive proa ss 
 upon living cells — i. e., upon cells capable of responsive action — and 
 that the peculiar appearance of the gangrenous parts is due solely to 
 this cellular reaction. In other words, cadaveric putrefaction is 
 characterized by the development of saprophytes which act upon 
 dead matter, viz., matter incapable of reaction. On the other hand, 
 gangrene is characterized by the development of microbes which 
 attack healthy, sometimes profoundly altered cells, but cells which 
 have not passed into a state of vital indifference. Our definition 
 must, therefore, be somewhat modified, and, in order to sharply 
 distinguish gangrene from cadaveric putrefaction, we may state that 
 gangrene is essentially characterized by putrefaction of healthy or dis- 
 eased but still living cells. 
 
 Causes Favoring the Development of Gangrene. 
 
 Even when gangrene seems to be primary it develops only in deep 
 wounds which contain, in addition to the principal agent, a multitude 
 of pyogenic or saprogenic bacteria without the assistance of which 
 the process would not have occurred. 
 
228 
 
 INFECTIO US DISEASES. 
 
 In other cases gangrene appears as a secondary manifestation 
 
 either in the course of an infection or in a subject suffering from 
 seme noii-niicrobic disease. It generally develops in organisms 
 debilitated by cachexia, fatigue, or starvation. 
 
 Gangrene 'at times first occurs at a point of the economy which 
 was sj tared by the initial affection. When it develops in a locality 
 that is already the seat of a previous lesion it represents a local 
 epiphenomenon superadded to the pre-existing alteration. This is 
 observed in variola, varicella, even vaccinia, as well as in various 
 cutaneous affections, such as purpura, erythema nodosum, and 
 pemphigus. This is what is also observed in mucous membranes and 
 in the viscera. A great number of necrotic laryngites and ententes 
 and various forms of pulmonary gangrene belong in this group. The 
 .gangrenous process sets in and is assisted by a previous lesion. 
 
 When gangrene appears as a primary lesion its development is 
 facilitated by all causes which profoundly disturb the nutrition of 
 tissues, either directly (contusions, action of physical or chemical 
 agents) or indirectly. In the latter instance the influences favoring 
 the development of gangrene arise from vascular, nervous, or humoral 
 alterations — compression and obliteration of vessels, arterites, and 
 edemas. Symmetrical gangrene of the extremities is a good illus- 
 tration of the role of nervous alterations. 
 
 The following is a classification of the pathogenic conditions of 
 gangrene which, although artificial, is fairly applicable to the majority 
 of cases: 
 
 Conditions Predisposing to Gangrene. 
 
 ("Mechanical agents. 
 
 Physical agents. 
 I Chemical agents. 
 [Animate agents. 
 
 f Edemas. 
 
 | Vascular compression and oblitera- 
 ' Circulatory disturbances . -j tion. 
 
 Arteritis. 
 I Arteriosclerosis. 
 ( Central alterations. 
 Nervous disturbances . < Neuritis. 
 
 (.Raynaud's disease. 
 f Humoral and diathetic affections 
 (Bright's disease, diabetes, etc.). 
 Dystrophic disturbances . -j Autointoxications. 
 
 Exogenic intoxications, 
 [infections. 
 
 It is well to remark, however, that in reality the events are more 
 complex and that in a given case several pathogenic factors usually 
 intervene. Let us take, for example, the phenomena occurring in 
 cases of infection. The predisposing cause of the gangrene is repre- 
 sented by intoxication of the organism due to the secretions of 
 
 Indirect alteration of 
 tissues by . 
 
 Direct alteration of 
 tissues by . . 
 
QANQRENE. 229 
 
 pathogenic microbes, by alterations occurring secondarily in the 
 viscera and by disturbances of cellular metabolism. A a rule, 
 however, intoxication alone is tiol sufficient. Accounl musl betaken 
 of the local lesions secondarily caused by microbes in the skin or 
 viscera in the lung, for in tance ■■> well as of alteration* mani- 
 fested in the arteries, capillaries, and nerves. Moreover, we must 
 not overlook the fad thai fever diminishe the ecretions, notably 
 those of the mouth, and thai if the patienl i- no1 properly taken 
 care of the fecal matters and the urine soil the orifices and create 
 foci of putrefaction which deal the lasl blow to the failing resistance 
 of the organism. Hence, with (he progress of hygiene and antisepsis, 
 secondary gangrenes are of far less frequenl occurrence. 
 
 What has been stated with reference to infections may be repeated 
 in regard to each of (lie pathogenic processes above admitted. In 
 every instance the mechanism is complex. We shall endeavor to 
 briefly study each predisposing cause independently. 
 
 Role of Mechanical and Physical Agents. The important 
 traumatic mortifications caused by mechanical agents has been 
 demonstrated by numerous contributions of great interesl . In this 
 connection, Dr. Arloing's remarkable study of his bacillus hemine- 
 crobiophilus is worthy of consideration. This microbe is incapable 
 of producing gangrenous putrefaction in healthy tissues, but easily 
 invades tissues altered b}~ traumatism. The same is true as regards 
 the other agents of gangrene. Even the bacillus of gaseous gangrene, 
 if freed from toxin and introduced in small amount, gives rise to no 
 lesion. Lesions are produced, however, when it is deposited in a 
 muscle that has been subjected to violent contusion. 
 
 Analogous results occur when physical agents are permitted to act 
 upon tissues. Intense cold or excessive heat produces a series of 
 cellular mortifications. Small aseptic eschars may result, and in 
 connection with these the germs of gangrene may develop and give 
 rise to characteristic alterations in the tissues, as a consequence of 
 necrotic lesions or the formation of phlyctenular. 
 
 Physical agents, however, do not always act at the point of appli- 
 cation. A considerable number of observations tend to demonstrate 
 that exposure to sudden and intense cold may induce pulmonary 
 gangrene. In this instance the action of cold is probably indirect. 
 It is characterized by a spasm of the pulmonary vessels which, caus- 
 ing anemia in the tissues, rentiers them more vulnerable, and thus 
 favors the development of necrosing agents. 
 
230 INFECTIOUS DISEASES. 
 
 Role of Chemical Agents. As is known, chemical agents are 
 divided into caustics and toxics. 
 
 Caustics diminish the resistance of the tissues and may even pro- 
 duce necrosis liable to gangrenous putrefaction. This result, how- 
 ever, is rarely realized, and the action of caustics from the point of 
 view now occupying us is far less important than that of toxics. 
 
 Those toxic substances which produce gangrene at the point of 
 their introduction are very much like caustics. Venoms belong to 
 this group. The bites of snakes, of certain fish, the sting of insects 
 and scorpions may be followed by gangrenous phlegmons. Careful 
 researches, however, tend to demonstrate that the necrosis is due 
 rather to the microbes contained in the venom than to the venom 
 itself. The venom is to be credited only with the production of 
 cellular disturbances which facilitate the development of the microbic 
 agents. The situation is the same as the one resulting from the 
 infiltrations of bile or urine, except that the action of the venom is 
 more intense. In fact, the bile, when injected beneath the skin of 
 a delicate region — for instance, the ear of a rabbit — produces a 
 necrosis ending in the loss of a part of the organ. 
 
 The urine seems to be less harmful. Its action is due chiefly to 
 the distention of the tissues injected, which become thereby good 
 culture media for microbes. The conditions are the same as in the 
 experiment of Prof. Bouchard, who injected non-sterilizecl alimentary 
 substances beneath the skin of rabbits. The animals rapidly died 
 with gangrenous lesions infiltrated with gases. The subcutaneous 
 fluid swarmed with bacteria, but inoculation of the latter into 
 healthy animals produced no disturbances — the parasites were incap- 
 able of overcoming the resistance of a normal tissue. 
 
 Role of Circulatory Disorders. Any cause that diminishes the 
 nutrition of cells predisposes to gangrene. Samuel, experimenting 
 upon rabbits, produced anemia in the ear by ligating the carotid and 
 posterior auricular arteries. He then produced an intense inflam- 
 mation in both ears either by immersing them in hot water or by 
 rubbing them with croton oil. The healthy side rapidly returned to 
 a normal state, the anemic side became the seat of gangrene. The 
 writer has noticed that the results are the same when inflammation 
 is induced by means of the staphylococcus. Under these circum- 
 stances the anemic part presents lesions with gangrenous tendencies. 
 Similar facts are often noted in clinical observation. Senile gan- 
 grene, which invades a limb in which the artery is obliterated, and 
 
GANGRENE. 231 
 
 sphacelus consecutive to acute arteritis, are well known illustral 
 Venous obliterations may likewise favor the development of gan- 
 grene, but less frequently, since circulation U easily re-< tablished 
 by collaterals. 
 
 Edemas, no matter how caused, similarly dispose the pari 
 gangrene by distending the tissues and thus disturbing nutritive 
 exchanges. 
 
 Role of the Nervous System. The influence of the nervous 3ystem 
 in the pathogenesis of gangrene is beyond question. It will suffice 
 to recall the eschars which a1 I imes appear so rapidly in consequence 
 of some cerebral or spiii.-il lesion and the cases of extensive gangrene 
 following neurites, reported by Pitres and Vaillard. We may add 
 Raynaud's disease. The vascular disorders characterizing this affec- 
 tion explain the pathogenesis of those small eschars appearing espe- 
 cially in the fingers and toes — i. e., at points where multitudes of 
 saprophytes swarm, some of which may acquire pathogenic power. 
 The influence of nervous disturbances upon the development of gan- 
 grene is also evidenced by the experiments pursued by us with the 
 streptococcus of erysipelas. Section of sensory nerves augments the 
 intensity and duration of the lesions and favors the development of 
 gangrenous patches. 
 
 Role of Intoxications. The diseases that disturb the chemical 
 constitution of the organism, especially those inducing autoin- 
 toxication, induce gangrene by a highly complex mechanism, for, 
 when they last for a certain length of time they give rise to visceral 
 lesions and arterial and nervous alterations which contribute to the 
 development of sphacelus. Thus, in Bright's disease it is almost 
 impossible to determine the respective parts played by the various 
 lesions and by the blood alterations. The difficulty is equally as 
 great in diabetes. The arterial lesions, the nervous alterations, and 
 the dyscrasie modifications are alike responsible for the gangrenous 
 process. We have already recalled, in connection with suppuration, 
 the experiments of Bujwid and of Nicolas which demonstrate that 
 the staphylococcus aureus produces gangrene when it is inoculated 
 into a rabbit rendered glycosuric by intravenous injection of grape- 
 sugar. 
 
 The problem is still more complex when we consider exogenic 
 intoxications. The role of arterial spasm has been admitted by some 
 authorities to account for gangrenes produced by ergot. The experi- 
 ments of Robert have demonstrated that this action is due to a 
 
232 INFECTIOUS DISEASES. 
 
 special acid, sphacelic acid. Is it to be assumed that a spasm renders 
 the part anemic, and thus enables the microbes to develop? This 
 explication cannot be admitted without reserve, since the experi- 
 ments of Holmes and of Wernieh tend to demonstrate that ergot does 
 not produce a tetanic state in the small arteries, for tension is lessened. 
 
 Principal Agents of Gangrene. 
 
 Bacteriology of Gaseous Gangrene. The type of microbes capable 
 of giving rise to primary gangrene is represented by the bacillus of 
 gaseous gangrene, also called vibrion septique (Pasteur), bacillus of 
 gangrenous septicemia, bacillus septicus gangrence (Arloing), bacillus 
 of malignant edema, bacillus ozdematis maligni (Flugge) . 
 
 As is known, the microbe in question is an anaerobic bacillus, 
 generally occurring in the form of motile rods, measuring on an average 
 3/i in length and 1/jl in breadth. It occurs singly or in groups of 
 two or three, at times forming short chains. In cultures these 
 bacilli are, as a rule, solitary and, at the end of a certain length of 
 time, form undulating filaments sometimes assuming a spiral form. 
 The filamentous forms are observed in animals, notably in the blood, 
 where they reach a length of 20/* and even 40/*. They are easily 
 stained, but are decolorized by Gram's method. 
 
 The bacillus of gaseous gangrene is strictly anaerobic and develops 
 in various media, provided air is excluded from it. The cultures grow 
 at 68 F. (20 C), but are more luxuriant at 98.6 F. (37 C). This 
 bacillus is pathogenic for man, the horse, sheep, pig, and guinea-pig. 
 The rabbit is a little more resistant. The dog is rather susceptible. 
 
 The symptoms produced in man have been described under the 
 names malignant edema (Pirougoff, Koch), acute purulent edema 
 (Pirougoff), swift gangrene (gangrene foudroyante, Maisonneuve, 
 Salleron), invading traumatic gangrene (Bottini), gangrenous sep- 
 ticemia (Chauveau, Arloing). 
 
 The designation gaseous gangrene, proposed by Poncet, seems to 
 us by far the most preferable. It has the advantage of expressing 
 the two main manifestations of the morbid process. 
 
 Being anaerobic, this bacillus cannot vegetate in superficial wounds 
 exposed to the air. It invades only deep, contused wounds contam- 
 inated with dust. It rapidly develops in mortified tissue, giving rise 
 to patches of sphacelus and an exudation which exhales a fetid odor 
 and is filled with corrupt gases. At times the lesion spreads with 
 
QANQBENE. 
 
 extraordinary rapidity and causes death within n few daj , with 
 the appearance of general tnanifei tation which clearly Indicate the 
 profound intoxication of the organi m, and are expressed b) rapid 
 prostration, dyspnea, and, a1 the end, a fall of temperature. 
 
 Animals are liable to gaseous gangrene as well as man. A certain 
 muni ht of cases have been reported occurring in the hor e, co ■■•• . and 
 rabbit, after traumatism or parturition, Among laboratory animals 
 the guinea-pig is the most sensitive. 
 
 The results of numerous experiments demonstrate thai the bacillus 
 of gaseous gangrene acts the same as the saprophytes of putrefaction. 
 The value of the author's classification is thereby diminished, since 
 this microbe is not of itself capable of overcoming the resistance of 
 the organism, although it is (rue thai the same remark holds good 
 with regard to almost all pathogenic agents. 
 
 The Various Agents of Gaseous Gangrene. Along with the bacil- 
 lus of gaseous gangrene are to be classed a scries of microbes which 
 are more or less similar to it in their biological or pathogenic 
 characters. 
 
 One of them is the bacillus of symptomatic anthrax, 1 which has 
 sometimes been considered a particular species, sometimes a variety 
 of Pasteur's bacillus. It differs from it by its pathogenic properties. 
 It attacks mostly cattle and sheep. The ass, horse, and white rat 
 present only local symptoms. The dog, cat, pig, rabbit, chicken, 
 pigeon, and duck are refractory, while the guinea-pig is as sensitive 
 to it as it is to gaseous gangrene. No case of transmission of the 
 disease to man has thus far been reported. 
 
 Natural immunity, however, is no more absolute in this than in 
 other cases. The author has demonstrated that it is possible to 
 overcome the resistance of the rabbit to symptomatic anthrax by 
 several procedures : namely, by simultaneous injection of a living or 
 sterilized culture of the B. prodigiosus, of proteus vulgaris, or of 
 staphylococcus aureus — by injection of soluble substances extracted 
 from cultures of B. prodigiosus by means of glycerin and precipitated 
 by alcohol — by intravenous injection of soluble products of symp- 
 tomatic anthrax, and by inoculation of the virus into the anterior 
 chamber of the eye. Finally, as in the case of septic vibrio, animals 
 
 1 Arloing, Comevin, and Thomas. Recherches experiment ales sur la maladie infec- 
 tieuse appelee charbon symptomatique. Revue de medecine. 1SS0. 
 
 2 Roger. Contribution a l'etude experimental du charbon syniptomatique. Revue 
 de medecine, March and June, 1S91. 
 
234 INFECTIOUS DISEASES. 
 
 may easily be vaccinated against symptomatic anthrax by means of 
 living or sterilized cultures. The animals thus rendered refractory 
 furnish a germicidal and therapeutic serum. 
 
 Gaseous gangrene may also be produced by other microbes, such 
 as the pseudo-cedem bacillus of Liborius {B. pseudosepticus, Mace),. 
 the B. phlegmones emphysematosa (Fraenkel), or B. perfringens 
 (Yeillon and Zuber), which is an anaerobic; B. cedematis aerobicus 
 of Klein, the B. pseudo-oedematis maligna? of San Felice, and the 
 aerobic septic bacillus recently described by Legros and Lecene. 
 
 Necrosing Role of Pyogenic Microbes. Of the micro-organisms 
 above described, several which produce gaseous gangrene in certain 
 animals are simply pyogenic for more resistant species. Recipro- 
 call}'', common pyogenic germs are capable, under certain circum- 
 stances, of creating gangrenous lesions. 
 
 The streptococcus is the leader of those pyogenic germs which 
 occasionally become capable of giving rise to necrosis. This seems 
 to be the microbe causing the experimental disease which Koch 
 produced by inoculating putrid substances into the mouse and which 
 he designated as progressive necrosis. We have repeatedly stated 
 that erysipelas produced in the rabbit's ear by the streptococcus may 
 terminate in sphacelation. On the other hand, injection of a culture 
 of streptococcus into the peripheral end of the crural artery in a 
 rabbit is at times followed by gangrene of the limb. We must add 
 that, under these conditions, examination of the mortified parts 
 shows numerous auxiliary microbes, but these occupy the most 
 superficial parts and evidently play a role of secondary impor- 
 tance. 
 
 Analogous facts are observed in man. Intense erysipelas of the 
 face often produces necrosis of the eyelids. The same is a possible 
 event with regard to the testicles. Erysipelas may be followed by 
 gangrene of the scrotum. In a case of complete sphacelation of the 
 scrotum the skin was gradually detached and the testicles exposed. 
 This was then followed by active granulation, and the lesion was 
 completely repaired. 
 
 Another pus coccus, the staphylococcus aureus, may also produce 
 gangrene. This, like the streptococcus, is a facultative anaerobic. 
 The experiments of 0. Bujwid establish that the staphylococcus 
 engenders gangrene in animals rendered glycosuric. Other observa- 
 tions tend to show, though not conclusively, that this micro-organism 
 may also produce gaseous gangrene. Lastly, there is the bacillus 
 
QANOBENE, 
 
 proteus, the action of which is incontestable, irice il 
 microbe endowed with a high degree of fermentative power. 
 
 Gangrene in Various Parts of the Organism. 
 
 Cutaneous Gangrene. The majority of cutaneous lesion maybe 
 complicated by gangrene. No1 to mention anthrax and erysipelas, 
 which have already been referred to, we should liketorecall the 
 sibility of gangrene in connection with the mosl varied and al times 
 
 the slightest lesions, such ;is impetigo, variola, vaccinia, ecthj 
 herpes, zona, purpura, and even urticaria. Sphacelation Lb favored 
 by all debilitating causes, and often coincides with visceral lesions, 
 diarrhea, and bronchopneumonia. In other instances gangrene of 
 the sacrum is observed in the course of convalescence from a grave 
 disease. A cerebral or spinal lesion is at times responsible for the 
 gangrenous process. If is readily conceivable that, under these 
 various conditions, the pus cocci and saprophytei — aormal residents 
 of the skin — may easily develop and. by their association, create 
 gangrene. 
 
 Gangrene of the Limbs. Instead of remaining limited to the Bkin, 
 gangrene may invade a more or less considerable part of a limb. 
 This is notably observed in the course of acute arterites consecutive 
 to infectious diseases. The lesion is due to the obliteration of the 
 vessel by a microbe — the streptococcus in the majority of instances. 
 The ischemia resulting therefrom leaves the tissues in a stal 
 absolute impotence against the toxins secreted by the pathogenic 
 agent and, incidentally, against the microbes tending to penetrate 
 the skin. 
 
 An affection which we have endeavored to individualize under the 
 name benign gangrene of the eyelids 1 is related to gangrenous 1< - 
 of the skin. The germ concerned in the lesion was a large micro- 
 coccus, staining by Gram's method, and developing preferably in 
 aerated media. 
 
 Gangrene of the Mammary Glands. Although the word gangrene 
 immediately suggests the idea of a grave process, we have ah 
 referred to cases in which the evolution is favorable and even be- 
 nign, as is often the case with gangrene of the eyelids and genital 
 organs. The same is true with regard to gangrenous mammitis. 
 
 Investigations in comparative pathology have shown the fre- 
 
 1 Roger and Weil. Gangrene benisrne tics paupieres. Presse medieale. 1 
 
236 I WFEl ' TH ' I 'S DISEASES. 
 
 quency of gangrenous mammitis in milk yielding females, notably 
 among bovidse. In a great number of cases the presence of strepto- 
 cocci of peculiar characters has been reported. Kitt, Lucet, and 
 Guillebeau have described other pathogenic agents. No researches 
 having been pursued as to the human species, reference must be made 
 to a case which the author studied with Dr. Gamier. 1 A woman, aged 
 seventeen years, had been confined on March 1, 1899. The child had 
 died two days later, without any definite cause. On March 7th she 
 complained of malaise and pain in the throat. On the 9th a typical 
 scarlatinal eruption appeared upon her body and she was imme- 
 diately sent to the isolation hospital of la Porte d'Aubervilliers. 
 
 From the time of her admission the state of her left mamma 
 attracted our attention. The skin of the region presented a diffuse 
 redness, especially marked toward the internal and lower part, where 
 two patches of ulceration with sphacelated base were noted. There 
 was abundant fetid discharge. Other smaller ulcers developed 
 around the areola. The gland itself was swollen and very painful 
 on palpation. 
 
 Moist dressings, constantly applied to the diseased region, in no 
 way modifying the condition, the odor of the purulent discharge soon 
 became plainly gangrenous ; the lesion itself began to spread, and the 
 ulcerations assumed a dark color. We then prescribed dressings with 
 peroxide of hydrogen. Improvement was immediately manifest. A 
 grayish eschar separated, eliminating the mortified glandular tissue. 
 Three weeks after the beginning of the disease cicatrization was 
 completed. 
 
 The pus taken from the wound was examined and cultured in 
 various media. Several series of inoculations with the pus were made 
 into rabbits and guinea-pigs, for which it proved pathogenic; less 
 so, however, for the latter than the former. The predominating 
 microbe was a small micrococcus whose clearly rounded elements 
 were usually solitary, sometimes associated in couplets, and excep- 
 tionally forming groups of three. They were free among the cells, 
 and none were found inside the leucocytes. In addition to this 
 microbe, some chains of streptococci were observed, but they were 
 comparatively few in number. 
 
 The results obtained by the several series of inoculations were 
 sufficiently uniform to demonstrate that the microbe isolated by us 
 
 1 Roger and Gamier. Note sur un cas de mammite gangreneuse. Lapresse medicate* 
 July 22, 1899. 
 
GANGRENE. 237 
 
 was a pathogenic agent, capable of giving rise to grave and < 
 suppurative lesions. The developmenl of the gangrenou mammitu 
 may, it seems to us, be legitimately attributed to thi microbe. 
 
 The micrococci round in the gangrenous mammifa of milk yielding 
 females may be compared to the one isolated by us in the human 
 subject, but the comparative study which we have pur ued -hows 
 that our microbe preserves its own individuality. I'- cultural char- 
 acters and its pathogenic action upon laboratory animate do not 
 permit its confusion with other species already described. 
 
 Gangrene of the Mouth and its Adnexse. There i an affection 
 of the mouth which may be looked upon as a superficial and benign 
 gangrene. We refer to what is improperly designated as ulcerative 
 membranous stomatitis. In reality, the so-called false membrane b 
 nothing more 11 inn I lie mortified mucous membrane. .Many authori- 
 ties have studied this affection with the view of detecting a specific 
 microbe, but with no encouraging results. Pasteur and Netter 
 observed the presence of spirilla in the patches. Fri'ihwald noticed 
 the same elements associated with cocci, bacilli, and filament- of 
 leptothrix. According to Gallipe, the probabilities are thai there is 
 no specific microbe and that the disease is created by buccal sapro- 
 phytes which have become exalted by various causes — the evolution 
 of a wisdom tooth, for instance. However, the researches of Vincent, 
 by proving that chancriform tonsillitis is due to the combined act inn 
 of the spirilla of the mouth and fusiform bacilli, give a certain value 
 to the older researches of Netter. 
 
 The true gangrene of the mouth — noma — is one of the affections 
 which has become rare, owing to the progress of antiseptic practice. 
 As early as 1878 Sanson noticed in the blood the presence of microbes, 
 but these were in nowise pathogenic. Jordan and Morse made 
 similar observations. During an epidemic of measles raging jn 
 Munich, Ranke had the opportunity to study six cases of noma. 
 Microscopic examination revealed numerous microbes, particularly 
 diplococci and streptococci, but inoculation into the rabbit produced 
 no result. By examining sections of tissues preserved in alcohol, 
 Rossi found masses of rods, staphylococci, streptococci, and lepto- 
 thrix. The results were analogous in a case studied by Babes, who 
 encountered leptothrix, spirilla, the streptococcus pyogenes, the 
 staphylococcus aureus, and an ovoid bacillus. In a more recent 
 contribution Babes announced that he had isolated a very slender 
 bacillus whose cultures injected into the cheek of a rabbit produced 
 
238 IXFECTIO US DISEASES. 
 
 a gangrene similar to noma. This highly interesting result is to be 
 classed with that obtained by Schimmelbusch. 1 In the case reported 
 by the latter authority there were found at the centre of the eschar 
 a multitude of various microbes. At the periphery, however, there 
 were none but slender bacilli, with rounded extremities, occurring 
 singly or in couplets, and capable of growing into filaments. Inocu- 
 lation of either the cultures or the mortified tissue into the rabbit 
 produced only abscesses. In two chickens patches of necrosis devel- 
 oped and were healed in three weeks. 
 
 Gangrenous angina is not always connected with the diphtheritic 
 process. It may be primary. Excluding the cases of superficial 
 gangrene, however, which are related rather to the study of pseudo- 
 membranous anginas, true gangrenous angina is a rarity. Out of a 
 total of 701 observations, the author has collected but three cases. 
 
 Gangrene of the Respiratory Apparatus. Two varieties of gan- 
 grenous processes may be distinguished. One, comparatively benign 
 and often curable, in which the superficial lesion remains limited to 
 the bronchi; the other, profound, invading the parenchyma. 
 
 In cases of fetid bronchitis the most varied microbes have been 
 found. Rosenstein met with the oidium albicans; Canalis, with 
 actinomycetes ; Ley den and Jaffe, with the leptothrix pulmonalis. 
 Lancereau observed diplococci; Marfan, the bacterium termo, and 
 Noica, the colon bacillus. One of the best studied observations is 
 that of Lumnitzer. He found four staphylococci: the S. albus, 
 citreus, cereus flavus, and cereus albus; one diplococcus, and one 
 bacillus. 2 
 
 Pulmonary gangrene has much oftener been the subject of bac- 
 teriological researches. As early as 1846 Virchow noticed in the 
 gangrenous fluids the presence of sarcina resembling those found 
 in the stomach. Fischer collected eighteen observations of this kind, 
 four of which are his own. 
 
 The most recent contributions show that the most varied microbes 
 may be encountered in the foci of pulmonary gangrene. Those most 
 frequently found are the buccal spirillum, the proteus vulgaris, the 
 streptococcus, the staphylococcus aureus, tetragenus, and the lepto- 
 thrix. Moreover, various pathogenic bacteria may be met with 
 
 1 Schimmelbusch. Ein Fall von Noma. Deutsche med. Wochenschrift, 1889, No. 26. 
 
 2 iAimnitzer. Adatok a rothaszto horglob koroktana es tiinettanahoz (contribution 
 to the etiology and symptomatology of putrid bronchitis). Orvosi Hetilap, 1888 (Anal. 
 Central, f. Bakteriologie, 1888, Bd. iii. p. 621). 
 
GANGRENE, 
 
 which vary from one case to anol her. ( ruillemol ,' who ha reported 
 the results of his studies in thirteen cases of pulmonary gangrene, 
 attributes an importanl rdle to anaerobic microbes in the production 
 
 of the process, and regards them even indii pen able. Ii i- true, 
 however, that these anaerobic agents are nol highly virulent. They 
 
 must be inoculated in I urge doses or associated with other species, 
 notably to aerobics, in order to give rise to morbid phenomena. 
 
 In two of the author's cases, one observed in L885 the other in 
 1895, the pulmonary gangrene seemed to have been produced by 
 saprophytes developed in a primary focus created by the pneumo- 
 coccus or streptococcus. In both cases, however, these cocci had 
 rapidly lost their virulence and had done no more than prepare the 
 soil for the developmenl of putrefactive agents. However thai may 
 be, the pyogenic micro-organisms seem to play an importanl role. 
 Issuing from a purulent focus, they have been known 1o be mi 
 in the lung and there form the starting point of a gangrenous lesion. 
 Bonome, who had the opportunity to examine nine cases of pulmon- 
 ary gangrene, found the streptococcus five times, the staphylococcus 
 three times, and once the two species together. 
 
 Babes also found the staphylococcus aureus in a case of pulmonary 
 gangrene. This micro-organism was associated with a bacillus which 
 produced a general infection and which the author described under 
 the name proteus lithalis. The latter appears in the form of small 
 rods, measuring from 0.8/* to 1.5/*, at times growing as filaments. 
 It is a motile, facultatively anaerobic microbe. Subcutaneous inocu- 
 lation gives rise to considerable edema and causes death in suscep- 
 tible animals — mouse and rabbit — in two or three days. 
 
 In a case of pulmonary gangrene which came under observation 
 of the author in 1900, the morbid manifestations — cerebral symp- 
 toms, difficult and slow response to questions, jerky delivery — led 
 him to think of some cerebral localization of the germs which had 
 •primarily affected the intestines. The necropsy did not, however, 
 reveal any appreciable lesion of the nerve centres, except a slight 
 serosanguinolent edema of the meninges. Except the intestines, the 
 abdominal organs presented nothing special. To come to the inter- 
 esting point, however, on continuing the necropsy, the right inter- 
 lobular fissure was found closed with soft, recent adhesions. In the 
 upper part of the lower lobe of the lung was discovered a large pouch, 
 the walls of which were 2 cm. to 3 cm. thick, containing about 100 
 
 1 Guillemot. Recherche sur la gangrene pulmonaire . These de Fari~. 1S99. 
 
240 INFECTIO I ft DISEA SES. 
 
 grams (over 3 ounces) of a fluid exhaling a fetid odor. The sac 
 was perfectly closed. The cavity was crossed by a bronchus, but 
 no opening was found — a fart which accounts for the absence of all 
 pulmonary sjmiptoms. 
 
 The data of the necropsy disclose the succession of the pathological 
 events. In order of date, the intestinal incidents were the first, and 
 the pulmonary lesion took its origin in the lesion in the alimentary 
 canal. 
 
 The microscopic examination of the fluid showed innumerable 
 bacteria. I shall confine myself to mentioning streptococci, large 
 micrococci, diplococci resembling those of pneumonia, bacilli recall- 
 ing the anthrax bacillus, and very slender bacilli which were often 
 united in masses. 
 
 The various observations briefly reported above show that the foci 
 of pulmonary gangrene contain, as a rule, pneumococci or pyogenic 
 germs associated with saprophytes. The latter may acquire no 
 virulence, as is proved by the negative results at times obtained by 
 inoculating the gangrenous fluid directly into animals and by employ- 
 ing the cultures, or else they become exalted and pathogenic. In the 
 latter instance gangrene is inoculable into animals, and its trans- 
 mission to man is then conceivable. It is to be noted, however, that 
 while the virulence of these necrosing agents is generally very ener- 
 getic, their development cannot occur in healthy subjects. In obser- 
 vations upon the contagion of pulmonary gangrene, the contaminated 
 individuals had already been suffering from respiratory affections. 
 Pulmonary gangrene is almost always the result of autoinfection. 
 
 The relative frequency of the various causes of pulmonary gan- 
 grene clearly appears in the statistics of Hensel, 1 according to whom 
 the most frequent causative lesion is embolism, represented by 20 
 cases. Of these 20 cases, 9 were pyemic emboli. Then follow the 
 other causes: pneumonia, 14 times; tuberculosis, 11 times; carcino- 
 mata in the neighborhood of the lungs, 10 times; bronchiectasis, 5 
 times; cerebral affections, 5 times; traumatism, 3 times. Lastly, in 
 three other instances, the lesions discovered were a perforation of the 
 esophagus and an abscess of the mediastinum — a focus of actinomy- 
 cosis — and suppurations of puerperal origin. 
 
 Gangrenous and Fetid Pleurisies. Pleurisies, the exudation of 
 which is characterized by a putrid odor, are commonly divided into 
 
 1 Hensel. Beitrage zur Casuistik des Lungenbrandes. Deutsches Archiv f. klin. 
 Medicin, Bd. xli. p. 185. 
 
GANGRENE. 241 
 
 two groups: gangrenous pleurisies consecutive t" sphacelation of 
 pulmonary tissue, and fetid or putrid pleuri " {pleur& ><■ ozSneu < 
 of Dieulafoy), which are produced in the absence of any primary i 
 in the subjacent organ. In the former ca 6 we have to deal with a 
 lesion created by propagation or rather contiguity. The pathogenic 
 germs have reached the pleura after invading the lung and engen- 
 dering a more or less extensive gangrene in its parenchyma, In the 
 latter instance, the microbes may possibly have penetrated l>;. 
 of the bronchi and the lungs, t raversing these organs without altering 
 them. More frequently they are derived from another region of the 
 organism, particularly from the alimentary canal. Dieulafoy hae 
 justly laid stress upon (he frequency and gravity of appendicular 
 pleurisies. 
 
 This at- present classical distinction seems to lie in harmony with 
 the etiology and pathological anatomy of the lesions. From the 
 pathogenic standpoint, however, the division referred to is less exact. 
 Whatever the variety under observation may be, the same microbes 
 are always met with — common pyogenic agents associated with 
 .saprophytes or numerous aerobic or anaerobic bacterial species. 
 In fact, the pneuniococcus, the streptococcus, the staphylococcus, 
 the tetragenus, the colon bacillus, B. proteus vulgaris, leptothrix, 
 bacillus of gaseous gangrene, the spirillum of the saliva, the B. 
 ramosus, the B. perfringcns, and the staphylococcus parvuhis have 
 been found in the pleural fluid. 
 
 Gangrene of the Alimentary Canal, Liver, Spleen and Genital 
 Organs. The great number of microbes swarming in the digestive 
 tract explains the frequency of gangrenous lesions observed therein. 
 In most cases, however, gangrenes are superficial and at the necropsy 
 appear under the form of simple ulcerations. On the other hand. 
 true, deep, invading gangrene is quite rare. It is observed especially 
 as a result of hernial or internal strangulations, by preference in 
 intestinal invaginations, as well as a complication of typhlitis and 
 appendicitis, exceptionally as a result of thrombosis of the mesenteric 
 artery. 1 No precise bacteriological examinations have been made in 
 such cases. We are not any better informed as to the superficial 
 gangrenes. The type of the kind is represented by dysentery. Even 
 though the etiological role of the ameba be admitted, it is not known 
 what part is played by the various microbes of the digestive canal. 
 
 1 Adenot. Thrombose de l'artere mesenterique inferieure et gangrene du c61on. 
 Revue de medecine, 1890. 
 
 16 
 
242 INFECTIOUS DISEASES. 
 
 The putrid germs may pass from the intestine into the liver and 
 there produce gangrenous abscesses. This is not an uncommon 
 occurrence in dysentery. The primary lesion is sometimes so small 
 as to escape notice, as is proved by an observation of Straus. 1 The 
 liver was the seat of numerous gangrenous abscesses the pus of which 
 was mixed with fetid gases. The spleen also contained a purulent 
 focus characterized by gangrenous odor, including detritus of spha- 
 celated tissue. Numerous microbes, which could not be cultivated, 
 were seen in the sections. 
 
 These various lesions of the intestine and its adnexse may, of 
 course, extend, to the peritoneum. 
 
 We have alreacty referred to gangrene of the genital organs, and 
 stated that in the male the external parts may become the seat of 
 gangrene consecutive to genital erysipelas and, in some cases, of 
 spontaneous gangrene characterized by an amazingly rapid course. 
 In the latter case large numbers of streptococci are found associated 
 with anaerobic germs. 
 
 Chemical Characters and Toxic Power of Gangrenous Products. 
 
 Chemical analyses of gangrenous products have demonstrated that 
 the amount of water increases considerably in moist gangrene. 
 Carbon diminishes, while it is augmented in dry gangrene (Raynaud 
 and Reveil). Albumins are broken up, and yield, on the one hand, 
 leucin and tyrosin; on the other, fatty acids which are, in some 
 instances, sufficiently abundant to impart an acid reaction to the 
 gangrenous fluid. These acids are mostly represented by butyric 
 and valerianic acids which give the focus its fetid odor. There are 
 also found gases, such as sulphuretted hydrogen and ammonia. 
 
 These various transformations are evidently related to the multi- 
 plication of microbes, and are due, in part at least, to the soluble 
 products or, more precisely, to the ferments secreted by the microbes. 
 This is demonstrated by the investigations of Filehne, Stolnikow, 
 and Escherich, who found in the sputa of patients suffering from 
 pulmonary gangrene a ferment which is similar to trypsin and 
 possesses the property of dissolving even elastic fibres. 
 
 Coincidently with the evolution of the local lesions are observed 
 a series of general phenomena of a serious character. Most of these 
 
 1 Straus. Sur un cas d'abces gangreneux, probablement primhif, du foie et de la 
 rate. Archives de med. exp., May, 1896, p. 428. 
 
GANGRENE. 243 
 
 may be ascribed to the microbic products, In fact, we '.now that 
 the Foci almost, ciiii;'.i:ini l\ <•< ,i 1 1 ; i i i j pyogenic cocci, of which we have 
 already studied the toxins, and we have further pointed oul that 
 very active substances are secreted by the bacillus of ga eom gan- 
 grene and I, lie oilier necrosing agent , 
 
 Some have recently attempted to belittle the rdle of pyogenic . 
 and Veillon, to whom we owe such valuable contributions upon 
 
 anaerobic- bacteria, has contended thai gangrene i always due to 
 anaerobic germs. This seems to the author to be an exaggerated 
 statement. The author thinks that along with the stricl anaerobics, 
 the influence of which has so well been proven by Veillon and his 
 collaborators, must be. classed certain microbes capable of living in 
 
 the presence as well as in the absence of air. ft is also to be QOted 
 
 that putrid decompositions are not always affected by strictly anae- 
 robic microbes. The colon bacillus is a first-class put refactive agent . 
 To be convinced of this, it suffices to smell the odor of certain 
 cultures. The author would therefore state, in conclusion, thai gan- 
 grene is a common process to which most varied microbe-, either 
 strictly or facultative anaerobics, may give rise. Of these microbes 
 a few are endowed with a high degree of pathogenic power, but this 
 is an exception. Most of them are no more than putrefact ive agents 
 incapable of developing in healthy tissues. They multiply only in 
 those parts of the organism which have been altered by previous 
 processes. They are able to induce grave manifestations by virtue 
 of the putrid poisons secreted by them. They are toxicogenetic 
 rather than infectious, and this is the reason the inoculation of 
 gangrenous products often gives rise to no disturbance whatever. 
 
CHAPTER IX. 
 
 SEPTICEMIAS AND PYEMIAS. 
 
 Definition of Words: Septicemias, Pyemias, Bacteremias, Bacteriotoxemias. Con- 
 secutive and Secondary Cryptogenetic Bacteremias. Septicemic Forms of Infec- 
 tions or Specific Septicemias. Agents of Septicemias and Pyemias. Experi- 
 mental Septicemias and Pyemias. Septicemias of Animals. Hemorrhagic 
 Septicemias. Study of the Epizootic Rhinitis of the Rabbit. Application of 
 Researches of Experimental and Comparative Pathology to Human Pathology. 
 Principal Clinical Characters. Evolution. Importance and Frequency of Atten- 
 uated Forms. Variolic Pyemia and Septicemia. Experimental Researches on 
 the Parasite of Smallpox; its Culture and Inoculabilitj r . 
 
 Definitions and Divisions of Septicemias and Pyemias. Septi- 
 cemia and pyemia constitute two morbid processes which must be 
 drawn nearer and united under the comprehensive term bacteremia. 
 In reality, the pathogenic germ either invades the whole organism 
 without creating special lesions (septicemia), or it locates itself in 
 certain viscera or tissues, and gives rise to the formation of purulent 
 feci (pyemia). In the latter instance a considerable number of small 
 abscesses are generally found at the necropsy occupying the liver, 
 kidneys, lungs, heart, etc.; these are designated by the rather im- 
 proper name metastatic abscesses. 
 
 Bacteremia must be distinguished from bacteriotoxemia in which 
 the pathogenic agent remains localized and gives rise to general 
 manifestations by means of the toxins it secretes. In bacteremia 
 there is general infection; in bacteriotoxemia, intoxication. 
 
 Bacteremia, then, includes both septicemia and pyemia. The 
 expression septicemia, created by Piorry, was to be applied to all 
 alterations of the blood produced by septic or putrid substances, 
 whatever their origin. After having been employed in most diverse 
 senses, the term was adopted by bacteriologists who have not suc- 
 ceeded in defining it any better than clinicians. Confusion was fur- 
 ther increased when the bacillus of gaseous gangrene was called 
 septic vibrio, and the disease induced by it gangrenous septicemia. 
 These improper terms led to important errors and nosological con- 
 fusion. Thus, for example, deceived by these words, some authors 
 believed that septicemia and pyemia should be separated on the 
 
SEPTICEMIAS AND PYEMIAS. 245 
 
 ground of thedifferent characters of their pathogenic agenl . Ace 
 ing to the expressions used by bacteriologists, septicemia was due 
 to an anaerobic bacillus, namely, septic vibrio, remaining a1 the 
 point of introducl ion; pyemia was dependenl upon aerobic microbes 
 invading the organism and there producing secondary absce i . 
 
 As a matter of course, a word may be employed in thi 
 attributed to it by an authority, provided il be well defined. Hence, 
 the term "septicemia" might be reserved for gaseous gangrene and 
 analogous processes. This, however, would be a notable departure 
 from the prevailing tendency, since, logically, il would be nece 
 to consider all local diseases which kill by intoxication as septicemias, 
 and thus include tetanus, diphtheria, cholera, etc., in this group: In 
 these 1 infections, as in the case of gaseous gangrene, the microbes 
 remain localized at one point, and, as their soluble secretions arouse 
 general reactions, the disease is of a toxic character. This is why 
 these diverse processes constitute a separate group — bacteriotoxemias 
 — and why gangrenous septicemia must be excluded from the group 
 of true septicemias. Thus limited, bacteremias still represent an 
 artificial nosological class; their existence may, nevertheless, be 
 rendered legitimate by the following considerations: 
 
 In cases of septicemia the microbe is present in every part of 
 organism; it may often be detected in the blood during life, 
 always after death. The lesions are those common to all grave 
 infections. The blood is disintegrated and dark in color: numerous 
 ecchymoses are found in the viscera and tissues. Hemorrhages are 
 at times so profuse that the affection deserves to be designated as 
 hemorrhagic septicemia. The microscope reveals small vascular 
 thromboses, cellular degenerations, and occasionally embryonic foci, 
 indicating a reactionary tendency on the part of the organism. Tin se 
 foci are limited, however, and are not visible to the naked eye. 
 
 At the end of a variable period of time, however, the microbes 
 become localized at certain points of the economy: septicemia then 
 loses the character of a general infection, and visceral localizations 
 become predominant features. The secondary foci then appearing 
 are, in some cases, simple inflammatory lesions: in other instances 
 they undergo purulent transformation. Under these conditions the 
 process might properly be designated as septicopyemia, representing 
 a transitional form between septicemia and pyemia. 
 
 Pyemias are distinguished from septicemias by the tendency of 
 the infectious agent to localize itself from the beginning in certain 
 
246 I. X FACTIOUS DISEASES. 
 
 viscera or tissues and there give rise to purulent foci. The germs 
 transported by the blood quickly leave this medium; hence the 
 assertion of some authors that in true pyemia the microbes are found 
 exclusively in the tissues. When they are at the same time encoun- 
 tered in the blood, the process should be held to be septicopyemic. 
 We shall see that this latter distinction is not well founded. 
 
 While septicemias and pyemias may produce anatomical lesions, 
 they may also be consecutive to some local lesion. According to 
 their apparent point of origin, two varieties may be admitted. The 
 first is characterized by invasion at once of the entire organism ; the 
 portals of entrance of the microbe and the initial lesion are wanting 
 or remain unperceivecl. The infection is then said to be spontaneous 
 or cryptogenetic. The latter epithet, introduced by Leube and 
 accepted by Jurgensen, is now frequently employed in Germany. 
 In the second variety, general infection is preceded by a local lesion. 
 Here two events are possible : sometimes the primary focus contains 
 the microbes which subsequently invade the economy, in which 
 instance bacteremia deserves the name consecutive ; sometimes, on 
 the contrary, the primary focus is the work of specific or non-specific 
 agents which do no more than provide a portal of entrance for the 
 microbe of general infection, in which case bacteremia is said to be 
 secondary. 
 
 According to the foregoing considerations, we may classify the 
 various types of septicemic and pyemic infections as follows : 
 
 Classification of Septicemias and Pyemias. 
 
 According to Their Origin. According to Their Evolution., 
 
 Primary: Without special localization (true septi- 
 
 Traumatic. cemias). 
 
 Cryptogenetic. 
 Consecutive. With inflammatory visceral localizations. 
 
 Secondary. With suppurative localizations: 
 
 Septicopyemias . 
 Pyemias. 
 
 May general infection ever be truly primary or, on the contrary, 
 is it always consecutive to a local lesion, such lesion being in some 
 cases so minute as to escape detection? The latter eventuality is 
 frequently realized. On the other hand, the reality of primary gen- 
 eral infections seems to be demonstrated by numerous surgical obser- 
 vations and experimental researches. Clinically, disturbances have 
 been seen to develop in consequence of an accidental, an operative, 
 or an obstetrical wound which seemed in good condition. The same 
 
8EPTI0EMIA8 AND PTEMIA8. 247 
 
 is true with regard to animals. When an extremely virulenl microbe 
 a certain streptococcus, for instance, i inoculated beneath the -kin, 
 death supervenes from bacteremia withoul the slightesl local lesion. 
 Furthermore, under a greal number of circumstances, the microbes 
 which we carry normally, notably those of the alimentary canal, i 
 penetrate into the economy, and, under debilitated conditions of the 
 system, they may a1 once induce a general disease. In Buch i 
 it is impossible to find a trace of their passage, for no lorn! lesion 
 exists, [f it were always possible to determine the mechanism of the 
 infection, occurrences of this kind should be grouped under the name 
 autobacleremia. 
 
 Consecutive go nc r; 1 1 infections are the mbsl frequenl as well as the 
 most important, since they include the greal majority of surgical 
 and obstetrical septicemias and pyemias. In this group should also 
 be included certain cases in which the primary lesion is of a medical 
 order, to wit, occupying such parts of the organism as to render 
 operative intervention impracticable. This evolution is met with not 
 only in suppurative lesions, but it is of constant occurrence in the 
 course of the most varied maladies. For instance, when an erysip- 
 elas or a pneumonia terminates in death, the infection nearly always 
 assumes a septicemic form. At the necropsy, and even during life, 
 the microbe concerned, be it the streptococcus or the pneumococcal 
 is found in all the organs and in the blood. 
 
 The same evolution may be observed with highly differentiated 
 bacteria. Anthrax is a good illustration. In man, the bacillas gives 
 rise to a local lesion, viz., a malignant pustule. Too often, however, 
 it crosses the barrier opposed, to it by the organism and invades the 
 whole system. The patient is then said to have died from anthrax 
 septicemia. It may happen, at least in animals, that even the local 
 lesion is absent, anthrax manifesting itself as a true septicemia. 
 
 It is likewise said that such or such an infection assumes a septi- 
 cemic form in cases in which it evolves without producing its usual 
 manifestations or lesions. Thus, a septicemic form of typhoid fever 
 has been described. It would, therefore, be easy to extend the limit 
 of septicemias so as to include almost all infections, at least certain 
 forms thereof. To avoid the confusion which would result from such 
 a conception, we are obliged to call septicemias those bacteremias 
 which are dependent upon common microbes, and to distinguish 
 those cases in which a well-defined agent has from the first or con- 
 secutively invaded the entire organism and behaved as in true septi- 
 
248 TNFECTIO US DISEASES. 
 
 eemia, as septicemic forms or specific septicemias. Thus, to take 
 the examples above referred to, we speak of a streptococcic septi- 
 cemia and a staphylococcic septicemia, whereas, if the question is 
 one of general infection by the bacillus anthracis, we employ the 
 expressions specific septicemia or septicemic form of anthrax. By 
 so doing we conform alike to clinical data and to the results of 
 bacteriology. 
 
 We believed it proper to sharply separate consecutive from sec- 
 ondary infections. The distinction is equally based upon clinical 
 experience and bacteriology. In consecutive infections it is the 
 same microbe that is responsible for all lesions. Let us take, for 
 instance, a purulent infection consecutive to a phlegmon : clinicalty, 
 it is the same process that has become generalized; bacteriologically, 
 it is the same microbe, staphylococcus or streptococcus, that is found 
 both in the initial phlegmon and in the metastatic abscesses. Pyemia 
 is then said to be consecutive. 
 
 On the other hand, let us take a case of diphtheritic angina. If 
 the patient succumbs to septicemia, as the latter is induced by the 
 streptococcus while the primary agent remains localized in the throat, 
 we say that this septicemia is secondary. It is a second process 
 superadded to the primary. Likewise, the arthrites of gonorrhea may 
 be produced by the gonococcus. This is an instance of consecutive 
 bacteremia resulting from the generalization of the principal infec- 
 tion. In other cases the arthrites are clue to an infection superadded 
 by a pyogenic micro-organism which has simply profited by the 
 urethral lesion and invaded the economy: this is a secondary 
 bacteremia. 
 
 Bacteriology. The author thought it well to include septicemias 
 and pyemias in one group. While pathological anatomy sharply 
 separates these two processes, clinical experience recognizes a close 
 relationship between them, and bacteriology confirms the results of 
 observation by demonstrating that the same pathogenic agents are 
 concerned in the great majority of cases. 
 
 There exist certain microbes which thus far have been met with 
 only in one of the two processes. This restriction, while preventing 
 a complete identification of pyemias and septicemias from an etio- 
 logical standpoint, is not of sufficient importance to separate the 
 two morbid groups. The most common agents of the two processes 
 are, in fact, streptococci and staphylococci, less frequently the other 
 bacteria to which reference has been made when treating of suppu- 
 
SHl'TWHMIAS AND PYEMIAS. 
 
 249 
 
 ration, and, lastly, in some cases, more or lei well-defined microbe* 
 
 or even simple s:i.| >roph yt es thai have acquired an unexpected < 
 
 Of virulence. 
 
 The same agents may cause septicemia in man and in animals. 
 In the latter, however, a greal number of speciei have been mel with 
 which thus far have nol been detected in man. Moreover, il i 
 to produce in animals experimental septicemias, thi tudy ol which 
 has largely contributed to the advance of bacteriology. We may, 
 therefore, divide septicemias into two greal groups: spontaneous sep- 
 ticemias — i. e., those occurring withoul any voluntary inoculation 
 and experimental septicemias. In the former group we may con- 
 veniently study the septicemias of man, affecting exclusively the 
 human species, or both man and animals, and septicemias attacking 
 animals only. 
 
 Experimental septicemias may also be subdivided into two 
 groups, according as (hey are produced by microbes derived from 
 living organisms or by saprophytes coming from putrefied substances 
 — air, soil, and water. 
 
 The following table will give an idea of the principal bacteria thus 
 far encountered. The list is necessarily incomplete, but its main 
 inconvenience is that it includes identical microbes as distant species. 
 In fact, it is known how difficult it is to determine the bacteria met 
 with. Hence, authors have often held as new such microbes as have 
 already been described, but the biological characters of which have 
 not been sufficiently indicated or have presented variations so pro- 
 nounced as to render their identification a matter of difficulty: 
 
 Principal Agents of Spontaneous Septicemias. 
 
 Of Man and Sometime* <>/ Animals. 
 Streptococcus. 
 Staphylococcus. 
 Pneumococcus. 
 Pneumobacillus. 
 Proteus hominis capsulatus. 
 Proteus vulgaris. 
 Proteus septicus. 
 Proteus capsulatus septicus. 
 Bacillus coli communis. 
 Bacillus of psittacosis. 
 Bacillus pyoevaneus. 
 Micrococcus tetragemis. 
 Bacillus of false anthrax. 
 Bacillus of hemorrhagic septicemia. 
 Bacillus septicus putidus. 
 
 Of Animals. 
 
 Bacillus of hemorrhagic septicemia. 
 
 Chicken cholera. 
 
 Disease of pigeons. 
 
 Disease of canaries. 
 
 Cholera of ducks. 
 
 Infectious enteritis of chickens. 
 
 Septicemia of rabbits. 
 
 Purulent rhinitis of rabbits. 
 
 Septicemia of ferrets. 
 
 Disease of wild animals. 
 
 Septic pleuropneumonia of calves. 
 
 Contagious pneumonia of pigs. 
 
 Infectious pneumoenteritis. 
 
 B. of septicemia of rats. 
 
 B. capsulatus. 
 
 B. hydrophilus fuscus. 
 
250 IXFECTIO US DISEASES. 
 
 Experimental Septicemia. 
 
 Of Animal Origin. Of Saprophytic Origin. 
 
 Agents of septicemias of salivary or Septicemia of Coze and Feltz. 
 
 nasal origin: Septicemia of Davaine. 
 
 Bacillus salivarius septicus. Experimental septicemia of mice. 
 
 Micrococcus salivarius septicus. Experimental septicemia of rabbits. 
 
 B. crassus sputigenus. Bacillus septicus agrigenus. 
 
 B. smaragdinus fetidus. B. canilicolis brevis. 
 
 B. salivarius canis. 
 Agents of sejDticemias of intestinal 
 origin: 
 
 B. cavicida havaniensis. 
 
 B. caniculicida havaniensis. 
 
 B. acidiformans. 
 
 B. leparis lethalis. 
 
 Streptococcus. 
 
 The agents of pyemia are far less numerous. The principal ones 
 are the streptococcus and staphylococcus, to which may be added a 
 special bacillus described by Levy. 
 
 Certain more highly organized parasites may be classified with the 
 agents of pyemia: actinomycetes, for example, which induce even in 
 man multiple suppurations, and thus give rise to a true chronic 
 pyemia. The oospora farcinosa and oidium albicans are capable 
 of acting in a similar manner. These various pyemias, however, 
 should be considered as specific pyemias. The common pyemias are 
 almost always dependent, in animals as well as in man, upon the 
 habitual agents of suppuration — streptococci and staphylococci. 
 
 Experimental Septicemias and Pyemias. 
 
 The study of septicemias and pyemias which may experimentally 
 be produced in animals is of great importance in medicine, since it 
 has powerfully served to establish the fundamental principles of 
 bacteriology on solid bases. These experimental maladies may very 
 readily be produced; it suffices to inject into animals saliva or fecal 
 matters, to inoculate putrefied substances, or contaminated water, 
 or to introduce dust beneath their skin. Many experimenters eagerly 
 entered this field of research and described a great number of experi- 
 mental diseases characterized by septicemic manifestations. 
 
 Researches of this kind are, at present, rather neglected; it would 
 be of value, however, to pursue such investigations in order to 
 demonstrate what relationship exists between diseases caused by 
 saprophytes swarming in putrid matters or found in the air, soil, and 
 water, and spontaneous diseases, developing without any experimen- 
 
SEPTICEMIAS AND PYEMIAS. 251 
 
 tal influence, Important data may thus be obtained regarding the 
 distribution of pathogenic agents outside living being and the i o 
 sible sources of contamination. 
 
 History. We shall not dwell upon the work* of the pre-bacterial 
 period ; a very full account of them \\ ill he Ion ml in tli'' highly inter- 
 esting article of .Icnimel. 1 li will suffice to recall thai Gaspard wae 
 the first to undertake experimental researches upon purulenl and 
 putrid infections. 2 The results were verified by Magendie (1824 
 Trousseau and Dupuy (1826), Leurel (1826), Boyer (1834), etc. In 
 a remarkable work d'Arcel demonstrated thai putrid serosities give 
 rise to putrid infections without abscess; thai flic injections of pus 
 generally cause death without lesions (1842). The pathogenic idea 
 of d'Arcet was developed by Virchowand accepted by many authors; 
 pyemia was considered as a septicemia complicated with embolic 
 migrations. In 18S9 Verneuil stated thai pyemia is an embolic 
 septicemia and that purulenl infect ion is a termination of septicemia. 
 
 The researches of Berard, Oastelneau, Ducret, Sedillot, Batailhe, 
 •Gamgee, Chauveau, Billroth, and 0. AA'eber established experimen- 
 tally that putrefied pus induces septicemia without abscesses, while 
 fresh pus gives rise to septicemia or pyemia — a septicemia when a 
 great amount of pus is at once introduced; a pyemia when small 
 doses are injected and the inoculations are repeated several days 
 in succession. The possibility of reproducing in animals the two 
 infectious processes which were known to clinical experience led 
 naturally to investigation of the mechanism of the events. A few- 
 authors believed that pus was engendered by the white corpuscles : 
 such was the opinion of Sedillot, Billroth, and 0. Weber. 
 
 In order, however, to explain the general phenomena and the mode 
 of development of septicemias, another factor was to be taken into 
 account. This factor was first looked for in chemical substances. 
 The toxic theory, which contains a great deal of truth, was further 
 developed by the works of Panum. It is well demonstrated, in fact, 
 that the symptoms observed in infections depend upon toxic sub- 
 stances ; but by what mechanism are the latter produced? Pasteur's 
 works, by showing the animate nature of fermentations, led to a 
 search among the infinitely small for the cause or, at least, the start- 
 
 1 Jeannel. Art. Septicemic et pyoh&nie. Encyclopedic intemationale de chirurgie, 
 1883, t. i. p. 311. 
 
 2 Gaspard. Memoire physiologique sur les maladies purulentes et pumdes et sur la 
 vaccine. Journal de Magendie. 1S'2'2. p. 1: 1S24. p. 1. 
 
252 INFECTIOUS DISEASES. 
 
 ing point of the events. Thus we arrive at the second or microbic 
 period of the history of septicemias. 
 
 From 1S65 to 1S69 Coze and Feltz 1 published a scries of researches 
 on septicemia. They succeeded in inducing septicemic conditions 
 by various procedures. Sometimes they introduced putrid sub- 
 stances beneath the skin of clogs and rabbits; in other cases, they 
 introduced blood derived from typhoid fever, variola, puerperal fever, 
 or scarlatina patients. In all instances the animals died, and the 
 necropsy revealed in the blood a great number of microbes, bacilli, 
 cocci, and little chains. These authors must be credited with having 
 ( leveloped a fertile method of experimentation and having observed 
 an important result, to wit, the increase of virulence when inocula- 
 tions in series are made upon animals. This result was shown to be 
 verified by Davaine, 2 who left cow's blood to putrefy for ten days in 
 the month of July, and injected from two to fifteen drops of it into 
 rabbits, with a fatal result. By making successive inoculations,. 
 Davaine recognized that on the twenty-fifth passage the blood was 
 virulent in a dose of one-trillionth of a drop or at times even one 
 ten-trillionth of a drop (0.000,000,000.05 to 0.000,000,000,005 c.cm.). 
 He concluded that septicemia is a putrefaction effected in the blood 
 of a living animal by the activity of vibrios. 
 
 These results aroused doubt and criticism. Bouley, A r ulpian, who 
 had at first been skeptical, repeated Davaine's experiments, and 
 Behbier, as well as Liouville and Colin, recognized their exactness. 
 
 The next attempt was made with the view of discovering the 
 characters of the agents capable of causing such accidents. Popoff 3 
 made a first attempt by injecting into rabbits the yeast of beer and 
 a micro-organism cultivated in the urine. Klebs produced septi- 
 cemias by injecting cultures of putrefied tissue. Koch, 4 however, 
 should be credited with the first efforts to characterize and specify 
 the various experimental infections. This work, which is very 
 remarkable for the epoch at which it appeared, does not give suffi- 
 cient information as to the characters of the pathogenic agents, so 
 
 1 Coze and Feltz. Recherches exp. sur la presence des infusoires et l'etat du sang 
 dans les maladies infectieuses. Strasbourg, 1866-69. 
 
 2 Davaine. Recherches sur la septicemic et sur les caracteres qui la dissingue de la 
 maladie charbonneuse. Comptes R. Acad, des Sciences, Jan. 25, 1869. Recherches sur 
 quelques questions relatives a la septicemic Acad, de M6decine, September 17, 1872. 
 
 3 Popoff. Untersuchungen iiber die Wirkungen der Bierhefe und der in der Pas- 
 teurschen Flussigheit enthaltenen Organismen auf der thierischen Korper. Berlin, 
 med. Wochenschrift, 1872. 
 
 4 Koch. Ueber die Aetiologie der Wundinfectionskrankheiten. Leipzig, 1876. 
 
SEPTICEMIAS AND PTEMIAS. 
 
 that, with regard to several of th< m, it i difficull to determine their 
 relationship with the agents of other experimental diseasei and with 
 those of spontaneous infections. 
 
 Septicemias of Salivary Origin. Hitherto experimental septice- 
 mias were produced by injections of putrefied sub tanc< or patho- 
 logical products. The inoculation of normal organic fluids, however, 
 may produce the same results. In 1881 Pasteur obtained a septi- 
 cemia in the rabbit by inoculating the saliva of a boy the victim 
 of hydrophobia. Sternberg arrived a1 the same resull by injecting 
 the saliva of a healthy man; he carefully studied the characters of 
 this agent, and Fraenkel demonstrated its identity with the pneumo- 
 coccus. 
 
 At the present lime septicemias have been well studied and classi- 
 fied. We shall briefly indicate the characters of the principal ' 
 
 The inoculation of the saliva may give rise to several lorn. 
 septicemias in animals. The salivary septicemia with pneumococcus 
 is obtained by inoculating the rabbit or, better, the mouse. The 
 animal succumbs in twenty-four or forty-eight hours and the necropsy 
 reveals the easily recognizable encapsulated microbe in the blood and 
 organs. 
 
 The B. crassus sputigenus of Kreibohrn 1 is an encapsulated bacillus 
 analogous to if not identical with the pneumobacillus of Fried- 
 laender; it differs from it only in that it is not decolorized by Gram's 
 method. It kills mice and rabbits within twenty-four hours. 
 
 The B. tenuis sputigenus 2 is an encapsulated bacillus, smaller than 
 the preceding one, is stained by Gram's method and readily develops 
 in the various culture media. It is pathogenic for the rabbit and 
 white rat, but not for the guinea-pig and white mouse. 
 
 Aside from these septicemias produced by the human saliva, there 
 is one which Fiocca caused with the saliva of dogs and cats. It is 
 due to a small bacillus, which in cultures on potatoes resemble- a 
 micrococcus. It is a facultative anaerobic and does not liquefy 
 gelatin. The cultures are pathogenic for rabbits, guinea-pigs, young 
 rats, and mice. 
 
 Septicemias of Nasal Origin. Of the septicemias of nasal origin, 
 we must mention that which Reimann 3 has produced with a bacillus 
 found in a case of ozena: the B. smaragdinus fctidus. It is a facul- 
 
 1 Fliigge. Die Mikroorganismen. Leipzig, 1SS6, p. 2(30. 
 
 2 P;msim. Bakteriologisohe Studien des Auswurfs. Virchow's Archiv, Bd. exxii li 
 
 3 Reimann. Inaug. Diss., Wiirzburg. 1SS7. 
 
254 INFECTIOUS DISEASES. 
 
 tative anaerobic. Its intravenous or subcutaneous inoculation kills 
 rabbits in thirty-six or forty-eight hours; the necropsy reveals sub- 
 pericardiac and subpleural hemorrhages. Large numbers of bacilli 
 are seen in the blood and organs. 
 
 Septicemias of Intestinal Origin. The genuine microbe of septi- 
 cemias of intestinal origin is the colon bacillus. A great number of 
 infections attributed to other agents must be looked upon as due to 
 varieties of this microbe, viz., to varieties of B. coli communis and 
 B. lactis aerogenes. 
 
 The B. cavicida havaniensis (Sternberg), found in the intestine of 
 a subject dead from yellow fever, seems to be no more than a variety 
 of B. coli. It exerts no action upon rabbits and kills guinea-pigs 
 within ten or twelve hours. On the contrary, the B. cuniculicida 
 havaniensis (Sternberg), obtained under the same circumstances, is 
 a variety of colon bacillus which, as its name indicates, is pathogenic 
 for the rabbit. 
 
 The B. acidiformans (Sternberg), derived from the liver of various 
 cadavers, seems to the author to be analogous to the B. lactis 
 aerogenes. It Mils rabbits and guinea-pigs in twenty-four hours. 
 
 Septicemias and Pyemias of Saprophytic Origin. As has already 
 been stated, Koch had described several infections consecutive to 
 inoculations of putrefied substances. There is, in the first place, the 
 septicemia of mice, caused by the injection of putrefied blood. This 
 affection, which is due to a small bacillus measuring \fi by 0.1/^-, 
 attacks only the house mouse, not the field mouse or rat. By inject- 
 ing into rabbits an infusion of putrefied meat, Koch produced a new 
 septicemia, the septicemia of rabbits, due to microbes 0.8// to lft in 
 length. Gaffky observed a similar septicemia by injecting the 
 water of Panke into rabbits. The belief is now gaining ground that 
 all these affections depend upon the same microbe as that of chicken 
 cholera. 
 
 Sewer water and the soil contain a certain number of septicemic 
 agents, among j which are the B. canalicolis brevis and the B. septicus 
 agrigenus. The former was found by Mori in the sew r er water of 
 Berlin; it is pathogenic for mice, rabbits, and guinea-pigs, but not 
 for pigeons. The latter microbe, discovered by Nicolaier in manured 
 fields, resembles the bacillus of chicken cholera, but is a trifle longer. 
 When inoculated into the veins it kills rabbits in twenty-four or 
 thirty-six hours. It is also pathogenic for mice. 
 
 To sum up, the great majority of diseases experimentally produced 
 
SEPTICEMIAS AND PTEMIAS. 
 
 are due to microbes which we find in natural di ea e . [nm< 
 the same microbes under differenl names are encountered, notably 
 the streptococcus, pneumococcus, pneumobacillus, and colon bacillus. 
 Let us add the proteus vulgaris, tnirabilis, and Zenkeri, which are 
 so frequently present in decaying matters and the cultures of which 
 give rise to septicemias in animals, 
 
 Spontaneous Septicemias and Pyemias of Animals. 
 
 Hemorrhagic Septicemias. There exists a group of micr< 
 designated as bacilli of hemorrhagic septicemias, the importance of 
 
 which is far greater than was at first believed. Hie type of the kind 
 is represented by the bacillus of chicken cholera. It wassoon Learned 
 that the microbes of experimental septicemia produced by Koch and 
 Gaffky were no other than the bacillus of chicken cholera. It 
 later recognized that a great number of affections observed in bird-, 
 cows, wild animals, and the hog depend upon microbes analogous to 
 or identical with the bacillus of chicken cholera. The presen< 
 this agent in putrefied substances (Koch) or contaminated water 
 (Gaffky) shows how widely it is distributed and explains the appa- 
 rently spontaneous development of certain epizooties. 
 
 The bacillus of hemorrhagic septicemia is the agent of at least 
 fifteen diseases that were once held to be different. In some recent 
 contributions, Dr. Lignieres introduces other affections, notably the 
 diseases of dogs and cats and the typhoid malady of horses, and pro- 
 poses to call the group pasteurelloses. Distinctions may be estab- 
 lished according to the species spontaneously affected and those which 
 may be infected in laboratories. It is to be noted, however, that 
 the pathogenic action varies considerably with the origin of the virus. 
 For instance, rabbits and chickens, which are so sensitive to chicken 
 cholera, are refractory to the other morbid varieties: while, on the 
 other hand, the guinea-pig, so slightly susceptible to chicken cholera, 
 may easily contract other forms of the infection. 
 
 It may, therefore, be questioned whether affections so clearly differ- 
 ing from each other can be classed in one morbid group. They have 
 been grouped for the reason that the pathogenic agents found in 
 these diverse diseases possess analogous or identical morphological 
 and biological characters. Morphologically, they are small, ovoid 
 bacilli measuring l/i by 0.25/*, and assume, in certain media, the 
 aspect of micrococci or diplococci. They are. with few exceptions, 
 
256 INFECTIOUS DISEASES. 
 
 non-motile. None is spore-bearing. Certain species, like that of 
 chicken cholera, cannot develop without oxygen; most of the other 
 varieties arc facultative anaerobics. 
 
 The differences existing between the various agents of hemorrhagic 
 septicemia recall those observable in the group of colon bacilli. The 
 comparison is the more interesting as the characters, considered as 
 distinctive, are the same in both instances. These consist in the 
 different appearances of the cultures on potato and in milk, the 
 production of indol, and motility and non-motility of the elements. 
 All these characters, however, are contingent and variable and do 
 not suffice to specify a microbe. The same is true as regards the 
 pathogenic action. The microbe of chicken cholera is extremely 
 virulent for the chicken and for the rabbit, while it is slightly so for 
 the guinea-pig; its inoculation produces nothing more than an 
 abscess in man, the horse, and sheep. 
 
 Such are the reasons which, since the works of Hueppe, 1 Baum- 
 garten, 2 Caneva, 3 and Bunzl Federn 4 have led to the creation of the 
 group of hemorrhagic septicemias. We should like to include in this 
 group the epizootic purulent rhinitis of the rabbit. 5 This affection, 
 of not uncommon occurrence, attacked some of the rabbits of our 
 laboratory in the spring of 1900. We then seized the opportunity 
 to take up the study of this malady. 6 
 
 Epizootic Purulent Rhinitis of Rabbits. The purulent rhinitis 
 starts with an abundant nasal discharge. The animal grows thin and 
 loses appetite. The discharge lasts about a week without any other 
 symptoms, and the affection invariably ends in death. In one case, 
 fatal termination seemed to be hastened by profuse nasal hemor- 
 rhages. At the necropsy upon these rabbits, the mucous membrane 
 of the nasal fossa? is found to be the seat of congestion ; the trachea, 
 bronchi, and sinuses of the face contain a clear, slightly purulent 
 mucus, and one is at times surprised at the absence of other micro- 
 
 1 Hueppe. Ueber die Wildseuche und ihre Bedeutung fur Nationalokonomie und 
 Hygiene. Berl. klinische Wochenschrift, 18S6, p. 753. 
 
 2 Baumgarten. Lehrbuch der pathologischen Mykologie, 1890, p. 489. 
 
 3 Caneva. Ueber die Bakterien der hamorrhagischen Septikamie. Centralb. f. Bak- 
 teriologie, 1891, Bd. ix., p. 557. 
 
 4 Bunzl Federn. Bemerkungen iiber Wild und Schweineseuche. Ibid., p. 787. Unter- 
 suehungen iiber einige Erkrankungen des Schweine. Archiv f. Hygiene, 1891. 
 
 5 There is a very interesting study on hemorrhagic septicemia in the book of Nocard 
 and Leclainche. Les maladies microbiennes des animaux, Paris, 1896. 
 
 8 Roger and Weil. Recherches bacteriologiques sur la rhinite purulente epizootique 
 des lapins. Arch, de m4d. exp., July, 1901. 
 
SEPTICEMIAS AND PTEMIA8. 257 
 
 scopic lesions. In certain cases, however, there is a marked pleni- 
 zation in the lungs, even hemorrhagei ; bh< o of the abdominal 
 
 cavity are congested, and the spleen enlarged. The pathogenic 
 agent, examined in the pus or in cultures, appear in the form of 
 oval elements which might easily be taken for micrococci. The} 
 small, non-motile bacilli measuring on an average 0.6// to 0.7//, 
 sometimes \/>. They are stained with difficulty and are decolorized 
 by Gram's method. Strictly aerobic, this microbe rapidly develops 
 in ox serum gelatin. Us vitality and virulence are well preserved 
 only in the serum of rabbits. Cultures made in this medium were 
 employed in our experiments and enabled us to produce in rabbits 
 a disease analogous to the spontaneous affection by its evolution and 
 lesions. 
 
 This disease of the rabbit lias been the object of two publications 
 in Germany. The first by dale is that of Beck, who isolated a 
 pathogenic bacillus comparable to that of human influenza. Krauss 
 found a bacillus which he believed represented a new species. Our 
 bacillus is not identical with the two preceding ones. Neverthe 
 it is quite likely that it is the same parasite assuming somewhat 
 peculiar characters according to various epizooties. 
 
 Human Septicemias and Pyemias. 
 
 The preliminary study above presented on experimental and spon- 
 taneous septicemias and pyemias of animals will facilitate compre- 
 hension of these infections in man. 
 
 Many pathologists divide septicopyemias into surgical, puerperal, 
 and medical. It seems to me more rational to take into account 
 both their point of departure and nature. We shall first study 
 primary, traumatic, and mitogenetic septicemias. They may be- 
 come manifest at once without any appreciable cause or in conse- 
 quence of a traumatism or important surgical operation. Dr. Jayle 
 has well demonstrated that a great number of cases considered as 
 instances of shock consecutive to. opening the abdomen must be 
 attributed to acute septicemia, commonly due to streptococci. A 
 second group includes septicemias consecutive to a local lesion. If 
 the latter is created by a highly differentiated micro-organism, the 
 septicemia is said to be specific and will not be dealt with here. We 
 are to study only those cases in which the lesion and its consequences 
 depend upon common bacteria, generally of the pyogenic group. 
 
 Finally, secondary septicopyemias are those in which the general 
 
258 INFECTIOUS DISEASES. 
 
 infection is induced by an ordinary microbe secondarily engrafted 
 upon a previous microbic lesion. 
 
 Bacteriology. The microbes commonly found in human septi- 
 cemias and pyemias are already known to us: they are chiefly the 
 streptococci," staphylococci, pneumococci, pneumobacilli, proteus and 
 colon bacilli. (See table, p. 249.) 
 
 Differentiation of the various microbes found in septicemias from 
 the pneumobacillus of Friedlaender has been based upon the results 
 of inoculations. In fact, it is admitted that the pneumobacillus is 
 not pathogenic for the rabbit. The author's 1 researches, however, 
 demonstrate that its intravenous inoculation gives rise to a fatal 
 septicemia characterized, in a great number of cases, by multiple 
 hemorrhages. This fact, which is contrary to classical opinion, must, 
 I think, be emphatically stated. As a result of intravenous inocu- 
 lations, there may be observed one of the following three types : 
 
 1. Hemorrhagic septicemia with swelling and infarction of Peyer's 
 patches, intestinal hemorrhages. 
 
 2. Septicemia, without any obvious lesions, with numerous mi- 
 crobes in the organs and the blood, or only in the organs — i. e., 
 without microbes in the blood, at least so far as microscopic exam- 
 ination reveals. 
 
 3. A chronic disease characterized by albuminuria associated with 
 renal alterations; at times by cardiac dilatations and paralyses. 
 
 These results seem to authorize us to more closely ally the pneu- 
 mobacillus with various encapsulated microbes pathogenic for the 
 rabbit. The manifestations observed are also interesting, because 
 they resemble those encountered in man and serve to elucidate their 
 mechanism. 
 
 The colon bacillus is very frequently concerned in septicemia. The 
 microbe of psittacosis, which does not differ greatly from this, may 
 be considered as a species intermedial between the colon bacillus 
 and the bacillus of Eberth. It was discovered by Nocard in diseased 
 parrots, and has been well studied by Gilbert and Fournier. These 
 authors have observed an epidemic attacking five individuals in one 
 family. Three were slightly affected; the two others succumbed in 
 eight or nine days. The microbe was detected at the necropsy in 
 the blood of the heart, and proved to be extremely virulent for par- 
 rots, mice, guinea-pigs, rabbits, and pigeons. Psittacosis manifests 
 
 1 Roger. Action du bacille cle Friedlaender sur le lapin. Soc. de biologie, January 20, 
 1894. 
 
SEPTICEMIAS AND PYEMIAS, 260 
 
 itself in man by symptoms resembling those of adynamic pneumo 
 of typhoid fever, with pronounced predominance of aervou pertur- 
 bations. 1 
 
 Although unable to affirm posil ively it pathogenic rdle, we hould 
 like to aote that the leptothrix buccalis ha al time invaded the 
 viscera. Poncel reports the observation of a patienl who succumbed 
 to a putrid infection consecutive to a dental abscess. Quantities of 
 this microbe were found in the metastatic foci and cardiac coagula. 
 
 Reference has already been made to the numerous investigations 
 willi regard to hemorrhagic septicemias of animals. No less impor- 
 tant researches luive been pursued with regard to hemorrhagic sep- 
 ticemias of man. II will si ill ice to mention those of Klebs, I feci, W. 
 (-Iicyiie, Petrone, Let/.erich, Dennne, and Illava. The last-named 
 author has even advanced the idea thai hemorrhagic fevers are due 
 to a superadded infection by a heinorrhagiparous bacterium. This 
 opinion will receive notice Later in connection with variola. In cer- 
 tain cases of hemorrhagic infection there has been found a bacillus 
 analogous to that of chicken cholera or rabbit septicemia. Tizzoni 
 and Giovannini, Babes, and Kolb have found a similar microbe in 
 purpura hemorrhagica. Babes further asserts thai this microbe is 
 present in the most varied infections — septic pneumonia, omphalitis, 
 keratitis, followed by hemorrhagic septicemia, hemorrhagic variola, 
 and septicemia resembling typhus fever. Belfanti and Pescarodo 
 have found the same microbe in a case of tetanus. Sternberg has 
 encountered it in the liver of an individual dead from yellow fever. 
 Lastly, we have found in a case of putrid pleurisy an analogous 
 microbe, present in the exudate with various other bacteria — viz.. 
 streptococcus, staphylococcus, and colon bacillus. It was the typical 
 aerobic, ovoid bacterium developing in agar-agar and gelatin, like the 
 microbe of chicken cholera. Its subcutaneous inoculation, even in 
 very small doses, produced in the rabbit a septicemia ending in death 
 within twenty-four hours, while in the guinea-pig there appeared at 
 the point of inoculation a profuse serous exudation, then an abscess 
 which opened in a few days and healed spontaneously. It is evi- 
 dently difficult to say what r61e had been played by this microbe in 
 the genesis of the symptoms presented by the patient; it is never- 
 theless interesting to call attention to the rare observations in which 
 the bacillus of hemorrhagic septicemia has been noticed in man. 
 
 1 Gilbert and Fournier. Contribution a 1 etude de la psittacose. Aeademie de m^de- 
 dne (report by Dr. Debove), October 20, IS96. 
 
260 INFECTIOUS DISEASES. 
 
 If we further bear in mind that the microbe of hemorrhagic septi- 
 cemia may be encountered as a simple saprophyte in the buccal 
 cavity of man (Baumgarten), dog, and cat (Smith), we shall conclude 
 that the microbes constituting this group must play in human path- 
 ology a role of greater consequence that was at first believed. 
 
 Relative Frequency of the Various Septic and Pyemic Agents. 
 Having briefly reviewed the principal microbes which may be found 
 in cases of bacteremia, we must determine the relative frequency of 
 each of them. The most complete study on this subject is that of 
 Canon, 1 whose investigations covered seventy cases. The author 
 divides his results into three categories, according as the process 
 was one of septicemia, septicopyemia, or true pyemia — i. e., pyemia 
 without the presence of microbes in the blood. 
 
 In the cases of septicemia, twenty in number, Canon has found 
 chiefly the streptococcus, less frequently the staphylococcus, once 
 the pneumococcus, at another time the colon bacillus, and, lastly, 
 in one case, an unidentified bacillus. These microbes were found in 
 the blood and in the primary focus. In two cases, however, the 
 initial lesion contained both the streptococcus and staphylococcus, 
 but the latter alone entered the blood. These results were secured 
 ■with blood obtained from the cadaver. Examinations made seven 
 times upon the living subject gave positive results in three in- 
 stances. 
 
 The second group comprises twenty cases of bacteremia with 
 metastatic foci. In eleven patients with various primary lesions 
 Canon found mainly streptococci and staphylococci, once the pneu- 
 mococcus, at another time a large unidentified bacillus. Out of five 
 examinations of the blood made during life, four yielded positive 
 results. 
 
 The author next reports five cases of osteomyelitis. With the 
 majority of German physicians he interprets this affection as a 
 pyemia of the developmental period. It is rather a staphylopyemia, 
 since out of the five cases the aureus was found three times, once 
 the albus, and once a diplococcus. Examination of the blood 
 during life gave positive results four times. In a last group the 
 report concerns cholelithiasis ; the pneumococcus and staphylococcus 
 were found. 
 
 1 Canon. Zur Aetiologie der Sepsie, Pyamie unci Osteomyelites auf Grund bakte- 
 riologischer TJntersuchungen des Blutes. Deutsche Zeitschrift f. Chirurgie, 1894, Bd. 
 xxxvii. 
 
SEPTICEMIAS AND PYEMIAS. 261 
 
 Finally, there remain those case in which tneta tatic foci 
 developed without any microbes being found in the blood. There 
 are cases of pure pyemia upon which Canon doe* nol dwell. 
 
 IViniKcliky' has :i.lso examined 59 ca e and Sittmann 23 ca 
 From these researches it is seen thai the microbe mo I frequently 
 encountered in bacteremia are the streptococcus and taphylococcus, 
 next comes pneumococcus, and then colon bacilli] , 
 
 Clinical Evolution. We do not intend to describe the ymptoms 
 and lesions of bacteremias; we shall confine our remarks to a 
 general considerations, the clinical history of these infections having 
 long since been known. 
 
 Bacteremias may occur under two quite distincl conditions. 
 Sometimes (here is a wound or a previous :i Iteration; sometimes the 
 organism is, or appears to be, normal. The first group includes 
 puerperal, surgical, and certain medical bacteremias, notably those 
 arising in the course or in consequence of eruptive fevers, anginas. 
 and tuberculosis. The second group comprises those cases in which 
 infection may be considered spontaneous or cryptogenetic. Puer] teral 
 infections are most frequently caused by the streptococcus. Accord- 
 ing to Morse, this micro-organism is found in 67 per cent, of the c. 
 The possibility of infection by the staphylococcus aureus and even 
 by the gonococcus has also been demonstrated. 
 
 The fact that the streptococcus is so frequently concerned in puer- 
 peral infection has confirmed the old observation of clinicians as to 
 the relationship between this disease and e^sipelas. It should not 
 be believed, however, that a puerperal woman suffering from erysi 
 elas is condemned to develop septicemia. The results obtained by us 
 are of a nature to render the diagnosis far less pessimistic. 2 Nineteen 
 patients affected with erysipelas were confined in our wards without 
 the occurrence of any symptoms of importance. The prognosis is 
 not any worse when erysipelas supervenes after confinement. ^ e 
 received nine women under these conditions: all recovered readily. 
 
 There is also a category in which puerperal infection appears spon- 
 taneously. Although the number of such cases is decreasing with 
 the advance of asepsis, the possibility of autogenic infection may be 
 admitted. The microbes develop owing to a profoundly weakened 
 condition of the organism, and infection is then prepared by digestive 
 
 1 Petruschky. Untersuchuiigen liber Infektiou mit pyogenen Kokken. Z<?itschr. fur 
 Hygiene, 1894. 
 
 2 Roger. iitude elinique de l'erysipele. Rev. de nied., 1S96, p. 236. 
 
262 INFECTIOUS DISEASES. 
 
 disturbances, putrid fermentations in the intestine, or some intercur- 
 rent affection, as well as by the retention of placental remains. The 
 last-named incidenl is of frequent occurrence, and gives rise to putre- 
 factions under the influence of saprophytes ; the products thus orig- 
 inated favor infection considerably. 
 
 We will not dwell at length upon the causes of surgical infection. 
 In some cases the wound is contaminated with germs, and general 
 infection follows at once. In other instances a local lesion is first 
 produced, which subsequently gives rise to general infection. Lastly, 
 infection may result from traumatism unattended by any 
 wound. Facts of the last category are exceptional. Wagner has 
 reported a remarkable example : it was a case of pyemia consecutive 
 to a fall upon the hip. When, however, bacteremia is consecutive 
 to a wound, it is not at all necessary for the latter to be a large one ; 
 serious phenomena have been seen to follow slight traumatism. 
 Landois cites a case of pyemia following a leech bite. It must be 
 acknowledged, however, that infection is favored by all causes that 
 produce severe attrition in soft tissues. Disinfection of such wounds 
 is difficult, and microbes find in contused and altered parts conditions 
 favorable to their development. Finally, with regard to surgical as 
 well as puerperal infections, the dominant etiological factor resides 
 in the transportation of germs by the hands of the operator or by 
 poorly sterilized instruments. 
 
 The last group, which also belongs in the domain of surgery and 
 medicine, comprises those cases in which bacteremia is consecutive 
 to an old lesion, for instance, suppurating wounds or deep-seated 
 lesions which scarcely admit of disinfection. It has already been 
 stated in connection with the process of suppurations that, in order 
 to explain generalization, it is necessary to assume a previous modi- 
 fication of the organism, probably through the agency of microbic 
 products originating in the primary focus. 
 
 If we now pass to medical affections, we likewise see that there is 
 no constant relation between the gravity of the primary lesion and 
 its tendency to generalization. Cutaneous suppurations, notably 
 those of smallpox, alterations of the tonsils, intestinal ulcerations, 
 lesions of the liver, urinary passages, and lungs, are the most frequent 
 causes of infection. 
 
 Lastly, there remains the group of cryptogenetic septicemias in 
 which general infection seems to occur spontaneously. This group 
 may be divided into two secondary groups. The initial lesion some- 
 
SEPTICEMIAS AND PTEMIA8. 268 
 
 times remains unnoticed, no1 having revealed il elf during life by 
 any appreciable symptom; it existed, neverthele , and wa found 
 at the necropsy. Ii may be a visceral uppuration, an intestinal 
 ulceration, an old locus within omi gland, etc. There are, bow 
 oilier instances in which the mosl searching post-mortem examina- 
 tion reveals no previous lesion infection bas been effected in the 
 absence of any starting point, [ncertainca i il development may 
 be accounted for bya previous state of general debility. It is highly 
 probable thai penetration of microbes into the system occur- con- 
 stantly, but they do mischief only when, as a resull of exhaustion 
 from overwork, or cold, or some other cause, the organism i- unable 
 to destroy the germs. Ii is to be acknowledged, however, thai there 
 are cases of infection which defy all explanation no cause can be 
 found to account for their development. 
 
 Infection may evolve as a septicemia without any localization. 
 The disease is characterized by intense initial chills, continued 
 fever, and a grave general state. The prognosis, however, is often 
 less serious than in cases of surgical or puerperal septicemia. 
 
 From the beginning or at a later period septicemia may become 
 localized in a viscus. At times localization is not clear, and must be 
 carefully looked for, or it may seem to be of little importance, as is 
 the case when it is expressed by an attack of albuminuria or the 
 development of an erythema. In other instances visceral localiza- 
 tion is the striking feature, while the septicemic phenomena tend to 
 amelioration. In such cases septicemia represents a period of tran- 
 sition leading to infectious localization, which then constitutes the 
 disease and develops on its own account. It is not rare to meet with 
 records of such instances in which general infection is scarcely referred 
 to, although it has been the cause of the localization which selects 
 the heart, vessels, lungs, or the liver, and may result in ulcerative 
 endocarditis, arteritis, phlebitis, bronchopneumonia, acute nephritis, 
 or diffuse hepatitis. 
 
 These various localizations are simply of an inflammatory nature: 
 in other cases, however, they may be expressed by suppurative 
 lesions ; septicemia then terminates in pyemia. It is certainly difficult 
 to say why a septicemic pathogenic agent may sometimes give rise 
 to suppuration. Some authors assume that the purulent function 
 already denotes a certain degree of reaction on the part of the system, 
 and that it may be accounted for by a moderate virulence of the 
 infectious agent. This same explanation has received a more scien- 
 
264 IXFECTIOUS DISEASES. 
 
 title formula. According to Sittmann, septicemia is of a toxico- 
 infectious nature: it occurs when bacteria find in the organism con- 
 ditions favorable for the production of poisons; in the contrary case 
 the bacteria are in part destroyed, and the proteins of their cadavers 
 excite the formation of pus. 
 
 The articular localizations of pj^emia had long been confounded 
 with articular rheumatism when Lasegue and Quinquaud individ- 
 ualized them. The latter author has described them under the name 
 arthrito-suppurative disease. The works of Prof. Bouchard and 
 Bourcy have conclusively established the nature of these infectious 
 pseudorheumatisms which sometimes occur in a primary manner and 
 sometimes appear in the course of or subsequently to the most varied 
 infections. What essentially characterizes this clinical type is that 
 the process involves only a small number of joints; the lesions mani- 
 fest a great tendency to become localized by preference in the knee- 
 joint, to undergo purulent transformation, or terminate in ankylosis. 
 This limitation of the process to a joint contrasts with the tendency 
 of polyarticular rheumatism to affect successively various joints. 
 Moreover, sweating and polyuria are absent in the former instance 
 and, finally, salicylate of soda is useless in such cases. 
 
 Pyemia with cutaneous or subcutaneous determinations is less 
 common. In the former case infectious erythemas and purpura 
 develop, with formation of pustulse and bullae filled wdth pus. There 
 is a clinical type in which the eruption of pustules, the so-called 
 pustules of Colles, are produced after an abrupt invasion character- 
 ized by chills, fever, and rachialgia. These manifestations subside 
 when the eruption appears. The latter consists of small pustules 
 surrounded by a red, inflammatory zone. At first sight variola may 
 be suspected, but a more attentive examination will enable one to 
 differentiate this subepidermic eruption from the eruption of small- 
 pox. 
 
 As an illustration of pyemias with subcutaneous determinations 
 we may cite an observation of Broca : A woman, aged twenty-nine 
 years, while nursing a patient with erysipelas, complained of malaise ; 
 ten days later she had chills and then developed multiple phlegmons. 
 Death occurred on the sixteenth day, and the necropsy demonstrated 
 the absence of any purulent focus in the viscera. 
 
 Attenuated Forms of Septicemias and Pyemias. The expressions 
 septicemia and pyemia suggest the idea of a serious, commonly fatal 
 process. Along with the acute forms, however, should be classed a 
 
SEPTICEMIAS AND PYEMIA8. 
 
 certain number of cases in which the procei become localized and 
 lends bo resolution. The manifestations may even be of an ephem- 
 eral character. Traumatic fever and milk fever are nothing bul 
 septicemic fevers so benign as to subside in fcwenty-four or f< 
 eight hours. The same is true as regards certain urinary fev< i 
 very short duration. 
 
 These remarks are also applicable to pyemias. Although the forms 
 in which numerous visceral foci exisl are necessarily fatal, there are 
 also benign forms in which localization takes place in some tissue, 
 for instance, in a joint, and in which cure is effected by a surgical 
 operation. Kven in grave eases of generalized i nice i ions recovery has 
 sometimes been obtained. If is mostly in septicemia without pro- 
 found cellular lesions that this happy result can be seen. In C 
 of generalized visceral pyemia attenuation or even destruction of the 
 agent avails nothing; the patient succumbs, not to the infection, bu1 
 to the visceral lesions resulting therefrom. 
 
 Variola, Pyemia and Septicemia. 
 
 The relations existing between septicemias and pyemias are clearly 
 evidenced by the study of a specific infection, variola, 
 
 The virus penetrates into the organism, probably through the 
 respiratory passages and invades the blood. Then reactionary mani- 
 festations of extreme violence appear. If the virus is very energetic 
 it produces profound cellular lesions and marked alterations in the 
 blood. Erythemata, purpura, hemorrhages in the skin, mucous 
 membranes, and principal organs are among the frequent events. 
 The individual succumbs in the absence of any tendency to suppu- 
 ration. It is a case of genuine hemorrhagic septicemia. 
 
 If the virus is less powerful, the expulsion of the parasite may be 
 effected. The organism eliminates it through the mucous mem- 
 branes and the skin, and papules appear at the various points by 
 which the microbes are rejected. A struggle is begun against the 
 pathogenic agent which results in the formation of pustules. There 
 is no intervention on the part of pyogenic cocci ever present in the 
 mucous membranes and integuments: suppuration is due to the 
 specific agent which thus gives rise to a pyemia with cutaneous 
 determination. 
 
 Between the two extreme types there are numerous transitions. 
 In certain cases, in the course of variolar septicemia, the organism 
 makes a last effort which is expressed by the development of a few 
 
266 IXFECTIO US DISEASES. 
 
 irregularly distributed pustules. On the other hand, a suppurating 
 variola may become modified in its progress by the occurrence of 
 secondary hemorrhages. Lastly, there exist some mixed cases of 
 infection in which pustules and hemorrhages make their appearance 
 synchronously. 
 
 These facts lead us to the conclusion that the pustules are the 
 result of the struggle against the parasite. When the virus is very 
 active the eruption is not produced; the patient succumbs to hemor- 
 rhagic septicemia. In fact, out of forty patients with primary 
 hemorrhagic variola admitted into our wards, none recovered. 
 
 In cases of pustular variola, the eruption is intense in proportion 
 to the abundance of the virus. From cases with confluent pustules 
 down to those in which the pustules are extremely rare or altogether 
 absent, there are numerous intermediate degrees. The cases with 
 no eruption are recognized only at the time of an epidemic. An 
 individual who has been exposed to contagion suffers, fifteen days 
 later, from chills, fever, and rachialgia. Four days later the symp- 
 toms tend to disappear without the appearance of eruption. Were 
 it not for the etiological data derived from the circumstances, a 
 diagnosis would be impossible. These facts were known to ancient 
 clinicians. Modern hematological researches have demonstrated 
 their reality beyond all doubt by showing in the blood the presence of 
 the special mononucleosis which is characteristic of variolar infection. 
 
 The ideas above expressed do not agree with the opinions of certain 
 authors who attribute to secondary infections a primordial role in 
 the evolution of variola. Some explain in this manner the purulent 
 transformation ; others admit, with Hlava, that hemorrhagic variola 
 is due to microbic association; superadded bacteria are supposed to 
 modify the course and aspect of the disease. It is true that pyogenic 
 bacteria are always found in the pustules, at least at an advanced 
 stage of their evolution, and that the streptococcus is constantly 
 detected in the blood and organs at the necropsy. In cases of 
 hemorrhagic variola this microbe is at times detected in the blood 
 during life. Hence, some bacteriologists considered the strepto- 
 coccus as the specific agent of the disease and designated it the 
 mriolococcus. The author believes too much importance is ac- 
 corded to this microbe, which must be looked upon simply as a 
 superadded agent aggravating the prognosis. He does not regard 
 it as the cause of the suppuration, since pustules may contain no 
 streptococci. He has often examined or sown the pus without being 
 
SEPTICEMIAS AND PYEMIA8. 267 
 
 able to detect any bacteria which could I"- tained or cultivated by 
 our present methods. In one case blood was drawn one hour before 
 death from the vein of the elbow of a patienl suffering from prin 
 hemorrhagic variola, and neither the streptococcus nor any other 
 bacterium was found. Pyogenic bacteria may likewise be ab 
 from even suppurative visceral lesion 
 
 On the other hand, experimentation demonstrate thai the pus 
 and at times the blood are virulent. Their inoculation into the 
 rabbit is followed by the development of a fatal disease which, 
 under certain conditions, may be transmitted in series. The blood 
 of the inoculated animals, taken during life, proves virulent, 
 although it is also devoid of bacteria. 
 
 Rejecting the bacterial origin of variola, we are led to the question 
 whether this disease is nol due to special parasites, and notably to 
 the protozoa that have been described by a few authors. 
 
 Microbiology of Variola. Dr. Renaul was the firsl to point out, 
 in 1881, special corpuscles in the pustules which he held to be para- 
 sites and to which he attributed a mechanical action in the formation 
 of the cutaneous cavity. Van der Loeff gave a fairly exacl descrip- 
 tion of these elements and, about the same time, L. Pfeiffer, widening 
 the range of the debate, published a series of highly interesting 
 researches upon the role of protozoa in the development of infections 
 and notably in vaccinia and smallpox. Guarnieri inoculated the pus 
 of variola or the fluid of vaccinia into the cornea of the rabbit: a 
 pustule developed, the stud)- of which showed strange figures inter- 
 preted by the author as the various phases of the evolution of the 
 parasite. From that time onward various contributions appeared, 
 and now there is general agreement as to the presence of small 
 special elements in the fluids of variola or vaccinia. It was rela- 
 tively easy to see these corpuscles, but difficult to determine their 
 nature and significance. "While the above-mentioned authorities 
 considered them as parasites, others could not see in them anything 
 but simple nuclear detritus. Such was the opinion of Salmon. 1 to 
 whom we owe a remarkable work of experimental criticism on this 
 subject. 
 
 From the very beginning of our researches on variola 2 we have 
 
 1 Salmon. Recherches sur 1 'infect ion dan* La vaccine et la variole. Annates de 
 l'Institut Pasteur, April. 1897. 
 
 2 Roger and Weil. Inoculabilite de la variole humaine an lapin. Soc. de biologie, 
 November 10, 1900. Recherches microbiologiques sur la variole. Ibid.. November 
 17, 1900. Recherches sur le parasite de la variole. Presse med.. November 2$. 1900. 
 
268 ISFECTIO US DISEASES. 
 
 noticed these special elements, and we have constantly observed 
 them in both man and inoculated animals. 
 
 It is not easy, however, to recognize these special elements. Some 
 of them are very small and do not measure more than 1/t; they may 
 then be confounded with micrococci. The largest elements attain a 
 length of 3« and simulate leucocytes. They are likewise found in 
 the blood, even in cases of varioloid. They are, however, more 
 numerous in grave cases and particularly abundant in hemorrhagic 
 forms. And j^et, even in the latter case, it is often necessary to 
 examine the preparation for a long time and search several fields of 
 the microscope in order to detect a single element. In the hemor- 
 rhagic forms the corpuscles are present in all extravasations of 
 blood, in hematoma, and in the urine in the case of hematuria; the 
 necropsy reveals their presence in the various organs, especially in 
 the spleen and bone-marrow. 
 
 Without dwelling upon all the arguments which tend to demon- 
 strate that these corpuscles are not cellular detritus, we shall mention 
 two necropsies which we had the opportunity of making at the begin- 
 ning of our researches. Two pregnant women, one of five and the 
 other of six months, having died from confluent variola, we took the 
 amniotic fluid which, in both instances, was clear and transparent. 
 Microscopic examination showed no leucocytes, but only desqua- 
 mated epidermic cells originating from the fetus and a considerable 
 number of corpuscles; we had never seen such a great number of 
 them. As the possibility of leucocytic detritus was precluded, it 
 seemed to us rational to admit that we were in the presence of para- 
 sites that had invaded the fetuses, in whose bodies a great quantity 
 of them was found, and had contaminated the amniotic fluid. The 
 motility of these elements in the amniotic fluid further confirmed our 
 view. They moved here with sufficient rapidity, while their move- 
 ment was not clear enough in the pus. 
 
 In order to be able to conclusively determine the nature and role 
 of the corpuscles, it was necessary to resort to experimentation. 
 
 Experimental Variola of the Rabbit. We looked for an animal 
 sensitive to the variolar virus, and we found the rabbit to be such. 
 
 If variolar pus free from bacteria and containing corpuscles only 
 is inoculated into a rabbit, the result is usually a fatal disease. If 
 the inoculation is made into the anterior chamber of the eye, a thick 
 exudate generally occurs at the end of twenty-four or forty-eight 
 hours, and heals up in five or six days. In spite of the disappearance 
 
SEPTICEMIAS AND PYEMIAS. 269 
 
 of the local lesion the animal continues to emaciate and dies on the 
 tenth to the twentieth day after inoculation, [f the pus La introduced 
 beneath the skin or injected into the veins, death supervenes, as in 
 the previous instance, at the end of two or three weeks. 
 
 The disease thus produced differs from human variola. The ele- 
 ment which seems to !"■ characteristic i. e., the pustule and which 
 only exceptionally is absent in man i- 3eldom observed in rabbits. 
 In three instances we saw a few papules develop on the fourth day 
 in the region corresponding to the subcutaneous inoculation, and 
 then resolve in forty-eighl hours. In one instance the eruptions were 
 more profuse, aboul twenty in number. 
 
 It is not without interest to note that, although the variola of the 
 rabbil differs from thai of the human adult, it resembles the variola 
 of the newborn. Children born of contaminated mothers succumb 
 to a slow septicemia. At times the eruplion is altogether absent; 
 in other cases there are but a few disseminated papules which, like 
 those of the rabbit, become covered with a crust and desiccate with- 
 out suppurating. 
 
 Bacteriological examination frequently reveals in man, as a super- 
 added bacterium, the streptococcus, more rarely the pneumococcal 
 while in animals a large bacillus is generally found. It is important 
 to remark, however, that in two out of every three cases, no microbe 
 whatever can be detected in the inoculated animals, while the cor- 
 puscles are constantly found. These possess the same appearance 
 and characters as in man. 
 
 The presence of these peculiar elements establishes a new analogy 
 between human and animal variola. This is not, however. abso- 
 lutely demonstrative of the parasitic nature of the corpuscles, since 
 it may be argued that the phenomenon is one of special alteration 
 produced in the cells of the organism by the variolar virus. It was. 
 therefore, necessary to follow the development of these corpuscles 
 outside the animal system. 
 
 Cultivation of the Microbe of Variola. We first studied what 
 occurs when the blood of the infected animal is placed in the incu- 
 bator at a temperature of 100.4° F. (38° C.) for twenty-four hours. 
 At the end of this period, microscopic examination showed that the 
 number of the corpuscles was considerably increased. Still the 
 increase was restricted and could not be compared with the rapid 
 multiplication of bacteria. 
 
 The next point requiring investigation was whether the corpuscles 
 
270 IXFECTIO US DISEASES. 
 
 which multiplied in the blood taken from the infected animal could 
 equally develop in the blood of normal animals. Starting with the 
 blood of an infected rabbit that had been kept in the incubator for 
 forty-eight hours, we once obtained eighteen successive cultures. 
 The corpuscles readily developed in them, retaining their primary 
 characters, except that they were somewhat larger in size, 2.5// and 
 at times 3,«. 
 
 It seems, therefore, reasonable to conclude that these elements are 
 true parasites. It is hardly necessary to add that we have often 
 assured ourselves that the blood of normal rabbits submitted to the 
 same process never presents such corpuscles. 
 
 A last point to be settled by experimentation still remained, viz., 
 the effects produced in rabbits by the inoculation of our cultures. 
 
 We made the same experiments as with the pus of variola, to wit, 
 we inoculated into the anterior chamber of the eye, beneath the skin 
 and into the veins, with substantially the same local and general 
 results, including, in some cases, the production of a small number 
 of papules, and terminating in death within a period of fifteen to 
 thirty clays. 
 
 Conclusions. Such are the results obtained bjr the experimental 
 study of variola. Although numerous, our observations and re- 
 searches are insufficient and incomplete. We may, nevertheless, 
 draw some conclusions from the accumulated facts. 
 
 As the corpuscles multiply outside the organism, in the blood of 
 infected animals, and even in defibrinated normal or incoagulable 
 blood, there is no logical escape from the conclusion that we have 
 to deal not with altered cells, but a parasite, probably a sporozoon, 
 especially when we remember the fact that these corpuscles are also 
 found in the amniotic fluid. 
 
 Although as yet incomplete, our experiments have some practical 
 bearings. The parasites which we studied being invariably present 
 in variola patients, we have been able, according as they were present 
 or absent in cases of doubtful diagnosis, to admit or reject the variolar 
 nature of the disease, and our conclusions were confirmed by the 
 ulterior evolution of the cases. We must remark that variola is not 
 the only infection in which these elements are encountered; similar 
 agents are also found in cases of vaccinia and varicella. This does 
 not necessarily mean that these infections are all due to a unique 
 agent, or that they are to be considered as various forms of the same 
 disease. These results merely indicate the relationship of the patho- 
 
SEPTICEMIAS AND PYEMIAS. 271 
 
 genie agents. Clinical observers have long been abb bo compare 
 certain eruptive fevers to variola. As is generally the case in Buch 
 matters, the analogies were first seen. Variola and varicella have 
 for a long time been identified. The identity of variola with 
 vaccinia has long been and is still ;i subjeel of controversy. The 
 microbiological study, in its presenl stage of development, shows 
 rather reseinhl.'iiices; l:iier on \i will reveal differential characters. 
 
CHAPTER X. 
 
 NODULAR INFECTIONS. 
 
 Mode of Development and Signification of Infectious Granulations. Infectious Nodules. 
 Microscopic and Macroscopic Nodules. Glanders. Characters of the Granula- 
 tions of Glanders; Their Analogy to Suppurative Lesions and to Tubercles. 
 General Considerations on the Bacteriology, Etiology, and Nosolog3 r of Glanders. 
 Tuberculosis. Characters of the Tubercle Bacillus. Mode of Propagation of 
 Tuberculosis. Pathological Anatomy of Tubercle. Histogenesis. Tubercular 
 Toxins. Sensitive and Refractory Animals with Regard to Tuberculosis. Tuber- 
 culosis of Various Mammalia. Avian Tuberculosis. Tuberculosis of the Gallinaj; 
 its Relation to Human Tuberculosis. Tuberculosis of the Psittaci. Unity of 
 Tuberculosis. Pseudotuberculosis. Study of Bacillary Pseudotuberculosis. 
 Oidiomycosis or Endomycosis. Biology of the Oidium Albicans; its Action on 
 Man and Animals. Oidian Granulations. Oidian Toxins. Vaccination and 
 Modification of the Serum in Animals Vaccinated against the Oidium Albicans. 
 Infections Produced by Yeasts. Actinomycosis. Characters of the Parasite. 
 Etiology of Actinomycosis; its Characters in Animals and in Man. The Various 
 Pathogenic Streptothrixae. Infections Due to Mucedinse and Aspergillus. Rela- 
 tion between Tumors and Infections. Inflammatory Tumors. Experimental 
 Tumors. 
 
 The development of microbic colonies often becomes a point of 
 attraction for wandering cells which accumulate in the form of 
 microscopic nodules. These are the infectious nodules, for the knowl- 
 edge of which we are indebted to Friedrich and E. Wagner. They 
 are considered by many authorities to be accumulations of cells 
 surrounding and circumscribing a microbic focus. This conception 
 is inexact, since such formations may, experimentally, be obtained, 
 especially in the liver, by injection of toxins. I have noted, for 
 instance, that the soluble products of the B. septicus putidus give 
 rise to the development of nodules; the only difference lies in the 
 fact that the nodules then appear more rapidly than in animals 
 infected by living cultures. 
 
 These nodules are held to be formed by round, indifferent cells, 
 at times designated under the improper name of embryonal cells, 
 which are sometimes supposed to have originated on the spot, 
 sometimes to have migrated from the vessels. Investigations have 
 convinced me, however, that the constitution of these nodules is 
 far more complex and varies according to the disease considered. 
 These productions may be expressed in cytological formulae exactly 
 
NODULAR INFECTIONS. -rr.\ 
 
 corresponding to those of the blood. Thui in variola 1 the nodulec 
 of the liver are constituted by more voluminou mononuclears. 
 Some have a clear nucleus surrounded by 8 protoplasm which can 
 be deeply stained; others contain a dark nucleus and a variable 
 amount of indifferent protoplasm. These cells are mingled with 
 connective (issue cells. The granular, inconstanl cell are, in some 
 instances, quite numerous: these are eosinophilic polynucl 
 neutrophilic mononuclears, and a few neutrophilic polynucl 
 Thus the same elements are found in the variolar nodulec as in the 
 hematopoietic organs, a fad which leads to the question whether 
 these nodules express a defensive reaction capable of arousing a 
 cytopoictic function which seemed In he extinct. 
 
 The diseases characterized by granulations establish a transition 
 between pyogenic infections and neoplasms. Certain pseudo- 
 tuberculoses resemble genuine tuberculosis in their macroscopic 
 characters; histological examination shows, however, that, in the 
 former case, the granulation is simply made up of a mass of unaltered 
 round cells. 
 
 The histoiy of tuberculosis furnishes a remarkable illustration of 
 the relations existing between suppurations, granulations, and neo- 
 plasms. In a certain number of cases Koch's bacillus gives rise to 
 cold suppurations ; it acts like a simple pyogenic agent. By a more 
 energetic action, it causes the formation of tubercles, the structure 
 of which is far more complex and characterized by the development 
 of epithelioid and giant cells. It is almost a tumor. In certain 
 animals the neoplastic evolution is complete; in the dog. tuberculosis 
 is expressed by productions presenting the appearance of sarcoma 
 and lymphadenoma. Microscopic examination alone is not suf- 
 ficient to reveal the nature of these tumors ; in order to demonstrate 
 their tubercular origin it is necessarj^ to resort to inoculation. 
 
 In the same order of ideas we may cite actinomyces which some- 
 times produces suppurating foci, and sometimes lesions that have 
 long been confounded with sarcoma. 
 
 In fact, it is well known that the most commonplace inflammatory 
 lesions may be followed by the development of a cancer. It is 
 hardly necessary to refer to the transitions which relate simple 
 gastritis to polyadenomata and epitheliomata of the stomach. The 
 line of relationship may thus be followed through these various 
 
 1 Roger and 'Weil. Note sur les nodules infectieux du foie d:\ns la variole. Soc. de 
 biologie, November 3, 1900. 
 
 IS 
 
274 INFECTIOUS DISEASES. 
 
 morbid processes. I had the opportunity to observe an experi- 
 mental fact comparable thereto. The inoculation of the staphylo- 
 coccus aureus Into the thyroid artery gave rise to the development 
 of a true tumor. I by no means wish to affirm the infectious origin 
 of cancer. I believe, nevertheless, that these few examples suffice 
 to show the reason why I place nodular diseases in a separate class 
 forming a transition between purulent infections and tumors. 
 
 Now, if we consider the entire group of diseases characterized by 
 granulations or nodules, we find the following in their order of in- 
 creasing complexity: 
 
 Glanders, which is rather akin to purulent infections; 
 
 Bacterial pseudotuberculosis ; 
 
 K 1 ycotic pseudotuberculoses ; 
 
 True tuberculosis, and 
 
 Actinomycosis. 
 
 Glanders. 
 
 Glanders is a virulent, contagious, and inoculable disease, occurring 
 particularly in the horse, the ass, and the mule, and may accidentally 
 be transmitted to various other animal species as well as to man. 
 
 Although one disease by nature, glanders may appear under 
 various clinical aspects. 
 
 Biology of the Bacillus. The bacillus of glanders appears in the 
 form of small, straight, or slightly curved rods, with rounded ends. 
 It is non-motile or endowed with simple molecular movements.. It 
 is very much like the bacillus of tuberculosis, but is a little thicker, 
 measuring from 2;i to 5// in length and 0.2/^ to 0.5// in breadth. It 
 is readily stained by various aniline dyes, particularly by alkaline 
 solutions, but is decolorized by Gram's as well as by Weigert's 
 method. 
 
 Being a facultative anaerobic, the bacillus of glanders readily 
 develops in the various media employed in bacteriology, provided, 
 however, it is placed at a sufficiently high temperature — i. e., at 
 98.6° or 100.4° F. (37° or 38° C.). A temperature of 131° F. (55° C.) 
 destroys the culture. According to Babes, the bacillus taken from 
 man or the horse does not develop except upon potatoes or in 
 bouillon; it can grow in agar-agar only after it becomes habituated 
 to these media, 
 
 The bacillus of glanders can hardly resist the causes of destruction 
 —exposure to air, sunlight, and heat, putrefaction, etc. The secre- 
 
NODULAR INFECTIONS. 275 
 
 tions of glandered animals rapidly lose their virulence; the pus 
 thinly spread and placed in a confined enclo lire become Inj 
 ;ii the end of two days, while in the central parte of an organ the 
 virulence may persisl for twentj six day (Cadeucand Mallet). The 
 cultures resisl longer, for a period of three or four month Loeffler). 
 
 Animals Sensitive or Refractory to Glanders. The animate mosl 
 liable to contracl glanders are the horse, the ass, the mule. Sheep 
 and goats also contracl ii easily, even spontaneously. The bovidas 
 are completely immune. 
 
 An ulcer which extends a little and then cicatrizes and heals i- 
 observed at the point of inoculation in the dog. The ca1 is highly 
 sensitive to glanders; ;it the end of eigjbl days its articulations 
 are invaded, and it often succumbs within two weeks (Lisitcyn . 
 The disease 1 has also been observed in wild animals Qourished in 
 menageries with contaminated meat. 
 
 Among the small animals we will cite the guinea-pig, which ha- a 
 pronounced receptivity. The rabbit is far less sensitive than the 
 guinea-pig. With the various species of mammalia, inoculation 
 into the nerve centres offers a very sure procedure for communicating 
 glanders. Success is thus obtained, even with refractory animal-: 
 while in those which are susceptible, a disease with a particularly 
 grave and rapid evolution appears, and the virulence of the bacillus 
 is found to be exalted. 
 
 Birds are very slightly sensitive to glanders: they might even be 
 said to be refractory, excepting the pigeon, the immunity of which 
 is incomplete. 
 
 Etiology. It was for a long time admitted that glanders may 
 originate spontaneously, at least in the horse. At present it is known 
 that this disease cannot occur except by contagion, either through 
 direct inoculation, or through infection. It is, nevertheless, certain 
 that a predisposition is created by a great many causes — fatigue, 
 bad nourishment, defective hygiene, etc. 
 
 Man hardly ever contracts the disease from any other animal 
 than the horse: it is, therefore, conceivable that it should be rare 
 among women; of the latter sex Bollinger finds only 6 out of a total 
 of 120 cases. 
 
 Since glandered horses are now being slaughtered, the frequency 
 of the disease has been rapidly declining. The persons affected 
 are naturally those working about horses — hostlers, veterinarians, 
 farmers, and the like. 
 
270 INFECTIOUS DISEASES. 
 
 In some instances the disease has been communicated by biting 
 (H. Landouzy). The result is not always positive, and everyone 
 remembers that CI. Bernard experienced no disturbance after being- 
 bitten by a glandered horse in the course of his experiments. 
 
 It has even been admitted that the virus at times may penetrate 
 through the intact skin. The experiments of Babes tend to support 
 this view. This author has seen a few guinea-pigs contract the 
 disease after a salve containing virulent bacilli was rubbed into the 
 healthy skin. Penetration is effected through the cutaneous glands. 
 Arrazat reported an observation in which glanders caused death 
 in ten days, and no wound of inoculation was discoverable. It 
 follows from Nocard's investigations, however, that the absolutely 
 healthy skin does not allow penetration — rubbing practised upon 
 three asses remained ineffective. Operating in the same manner 
 upon fifteen guinea-pigs, this author found that only two contracted 
 the disease, which latter result he attributes to the presence of such 
 abrasions as may easily escape detection. 
 
 The mucous membranes may similarly serve as routes of pene- 
 tration. There are on record several observations in which horse- 
 shoers contracted the malady by drinking from the same pail as 
 their horses, or wiping their noses with the rag which had been used 
 to cleanse the nostrils of the diseased animals. 
 
 The ingestion of infected flesh has communicated the disease, the 
 bacilli penetrating through the buccal or intestinal mucous mem- 
 branes. Bollinger affirms that the respiratory apparatus is another 
 portal of entrance, especially in those cases in which general symp- 
 toms precede local manifestations. 
 
 Pathological Anatomy. The granulation of glanders occupies an 
 intermediate position between suppuration and tubercle. In acute 
 cases it resembles rather suppurating lesions; in chronic cases it is 
 analogous to tubercular lesions. 
 
 The histological study of glanders has chiefly been made upon 
 lesions experimentally produced. The best descriptions are those 
 given by Baumgarten, Leclainche and Moutane, 1 and, above all, 
 by Lereclcle. 2 The first phenomenon is represented by an intra- 
 vascular accumulation of polynuclear leucocytes; the latter seize 
 upon the bacilli and arrive in such large numbers that they obstruct 
 
 1 Leclainche and Moutand. Etude sur l'anatomie pathologique de la morve pul- 
 monale. Annales de l'lnstitut Pasteur, 1893. 
 
 Leredde. Etude sur l'anatomie patholog. de la morve. These de Paris, 1893. 
 
NODULAR INFECTIONS. 277 
 
 the capillaries in which they accumulate. Thu i con tituted an 
 embryonal nodule. The cells then undergo degeneration, their 
 nuclei break up, and their protopla im become ca eou , The bacilli 
 iJuis liberated are taken up by Hie vascular endothelial cells, which 
 heroine tumefiei i. [f die evolution continue . Du •••'■ leucoc 
 assemble around the central caseous mass. 
 
 In chronic cases mononuclear leucocytes take pari in theproc 
 A sclerotic tissue develops which may be composed of small, caseouf 
 masses and giani cells formed a1 the expense of mononuclear leuco- 
 cytes. Owing to these cells, the histological constitution of the 
 lesion resembles the tubercular process. 
 
 This brief description shows thai the nodule of glanders us essen- 
 tially formed of wandering cells: first, polynuclear; subsequently, 
 mononuclear. Contrary to the opinion of Baumgarten,who attributed 
 to them the main role, the fixed cells of the tissues play a very 
 limited part in the process. 
 
 Tuberculosis. 
 
 The definition of tuberculosis 1 is at present furnished by the 
 pathogenic conception. It is the disease, or rather all the lesion-, 
 produced by Koch's bacillus. The knowledge of the pathogenic 
 agent has made it possible to trace a series of apparently dissimilar 
 manifestations to their true cause and to demonstrate the relation- 
 ship existing between the tuberculosis of man and that of animals. 
 
 Biology of the Bacillus. It is difficult to obtain a first culture of 
 tubercle bacillus. Either the organs of a guinea-pig inoculated with 
 human tuberculosis are taken as a point of departure, or, as Koch 
 and Kitasato have proposed, a particle from the central portion of 
 a mass of sputum is used. The cultures grow better in gelatinized 
 serum than in any other medium. At the end of ten or fifteen 
 days colonies appear which soon assume the form of well-isolated, 
 whitish or yellowish masses, composed of dry. roughened pellicles. 
 In successive cultures the masses coalesce to form dense and thick 
 membranes. 
 
 The tubercle bacillus is affected in a peculiar way by coloring 
 substances. Everyone knows the procedure of Ehrlieh which 
 enables us to distinguish this bacillus from all other microbes except 
 
 1 Tuberculosis, tubercle: Latin, (uberculum, derived from tuber, tumor. Both tuber 
 and tumor are formed from the Sanscrit radical tu. to grow. 
 
278 INFECTIOUS DISEASES. 
 
 that of leprosy. This procedure has undergone many modifications; 
 all the proposed methods, however, are based upon the following 
 fact — the microbe is with difficulty impregnated by the aniline dyes, 
 but once the dyes penetrate it retains them powerfully and resists 
 decolorization by dilute acids. 
 
 The bacillus appears in the form of small rods, usually measuring 
 from 3,u to 4,« in length and 0.3 ^ to 0.5/; in breadth; they are 
 straight or slightly bent, at times assuming the shape of an S, or 
 curved at one extremity. Their protoplasm is sometimes homo- 
 geneous, at other times formed of small ovoid or round grains. 
 In their interior are often observed colorless, oval vacuoles which 
 have, it seems, sometimes been mistaken for spores. 
 
 Until recently the agent of tuberculosis had been classed among 
 the bacilli. In 1884, Petrone, impressed by certain morphological 
 characters of the microbe, thought that it should be classed between 
 the micromyces and schizomyces. This opinion attracted no atten- 
 tion. Metchnikoff showed, however, that the bacillus sometimes 
 presents elongated, filamentous forms bearing terminal or lateral 
 enlargements. He finally pointed out the important fact that the 
 filaments may be divided. Maffucci argued that these various 
 phenomena are observed only in cultures of avian origin; and this 
 was then employed as an argument in support of the dualistic theory 
 of tuberculosis. It is at present known that the same forms, though 
 with some difficulty, may be obtained with human tuberculosis, 
 and, according to recent investigations, it seems certain that the 
 bacillary form of Koch's microbe is but a temporary, transitional 
 one, and that this parasite must be looked upon as a plant of rela- 
 tively higher development, belonging, with the actinomyces, to the 
 group of streptothrixge or oospora. It would, therefore, deserve 
 the name oospora kochii or tuberculomyces (C. Jones); it might 
 be called tuberculomyces hominis or T. avium, 1 according as the 
 microbe is of human or avian origin. 
 
 It is not simply for theoretical interest that we dwell upon these 
 results ; they enable us to correlate various pathogenic agents which 
 arouse comparable reactions in the organism. In fact, clinical ex- 
 perience had beyond all doubt recognized the relationship between 
 actinomycosis and tuberculosis; it is, therefore, important to point 
 
 1 Coppen Jones. Ueber die Morphologie unci systematische Stellung der Tuberkelpilzes. 
 Centralb. f . Bakt., Bd. xvii., 1895. Ueber die Nomenklatur der sog. Tuberkelbacillus, 
 ibid., 1896, Bd. xx. 
 
NODULAR INFECTIONS. 279 
 
 out that their pathogenic agents belong to closely allied botai 
 
 species. 
 
 The tubercle bacillus pre ents a very strong resistance to various 
 destructive agents. When dried, i1 preserves for a long time ite 
 noxious properties, especially when the surrounding temperature i- 
 low. Thus, according to Pietro, i1 remains virulenl for nine or ten 
 months at 77° V. (25° C), for two months al 86° or 95° I , 30° or 
 :tf° C), "'"'(I for one month al L22° I'. (50° ' 
 
 According to Cadeac and Mallet, fragments of tubercular lung 
 buried for one hundred and sixty-seven days produced tuberculosis 
 when they were inoculated into animals; beyond this period they 
 gave rise to septicemia; pieces of the same organ Left in water had 
 not yet lost: their virulence a1 the end of one hundred and twenty 
 days. 
 
 The tubercle bacillus is rather sensitive to the effect of heat; il 
 is killed by ebullition of a few minutes; when dried, it does not 
 resist the action of hot -water vapor. According to Galtier, however, 
 it- can endure a temperature of 140° F. (60° C.) for twenty minutes, 
 and one of 158° F. (70° C.) for ten minutes. Ebullition kills it 
 in five minutes (Sormani). The rays of the sun exerl the most 
 destructive influence and kill it most rapidly (Koch). 
 
 Etiology. The contagium of tuberculosis may be transmitted 
 from animals to man, from man to animals, from animal to animal, 
 and from man to man. 
 
 The contamination of man by animals raises several problems of 
 interest. In fact, it must first be questioned whether tuberculosis 
 is similar in all the animal species. If such is the case, as is now 
 generally admitted, is it dangerous for man to ingest the flesh, 
 viscera, milk, and other products of tubercular animals? The 
 muscles seem to have very little, if any, virulence. The milk, as 
 has already been stated, seldom contains bacilli, except in cases 
 of mammary tuberculosis. This source of danger, therefore, 
 although real, is not so great as was once believed, since mammary 
 tuberculosis is rare. Bang has observed only seven cases of mam- 
 mary tuberculosis in Copenhagen in the course of a year : in France 
 it seems to be still less frequent. 
 
 Among the products which are said to have transmitted tuber- 
 culosis, we may mention vaccine lymph. Since animal vaccination 
 has come into universal use the question has acquired particular 
 interest, the more so since Toussaint succeeded in inoculating tuber- 
 
280 IM-ECTIOUS DISEASES. 
 
 culosis through the agency of this fluid. This result has not been 
 confirmed, and the experiments of Lothar-Mayer, Straus, Chauveau, 
 Josserand, and Nocard demonstrated that the bacillus is not found 
 in the vaccinal fluid of either bovidae or man. 
 
 Finally, the dissemination of the bacillus through the urine of 
 dogs must be taken into account. Tuberculosis, which is not rare 
 among these animals, often involves the kidneys, and, in this case, 
 the agent passes into the urinary secretion. 
 
 The transmission of tuberculosis of man to animals has been 
 demonstrated by a great number of examples. 
 
 House animals such as dogs, cats, birds and, notably, parrots are 
 usually contaminated. 
 
 That transmission of tuberculosis does occur from man to man 
 and between animals of the same species is a truth demonstrated 
 beyond all possible doubt. 
 
 Flies ma}* carry tubercle bacilli (Spillmann and Haushalter), but 
 they disseminate rather than directly inoculate the virus. The 
 bacilli may likewise remain virulent for a long period in the interior 
 of earth-worms (Lortet and Despeignes). 
 
 Pathological Anatomy. Tubercular lesions assume two principal 
 forms: they may appear in the form of granulations, which are 
 peculiarly characteristic when examined in the serous membranes. 
 They are small, hard, non-enucleable nodules, often surrounded by 
 a red, vascular zone. Their size varies from 0.5 mm. to 2 or 3 mm. ; 
 they are at first translucent, but subsequently become opaque and 
 yellowish at their centres. They sometimes present rounded, gray 
 or yellow, isolated masses the size of a pea, a hazelnut, or even a 
 walnut (Laennec's tubercles), or they may form opaque deposits 
 infiltrating the tissues (caseous masses). In both instances the 
 lesion is essentially composed of granulations which cannot be 
 recognized with the unaided eye. 
 
 Alongside with these two principal types must be placed certain 
 alterations which, at first sight, appear absolutely different. Many 
 scrofulides, cold abscesses, lupuses, synovitis with riziform grains 
 are of tubercular nature. The same is true of certain cases of 
 pleurisy, although examination of the lungs does not seem to reveal 
 the presence of any specific lesions. 
 
 It may then be asked on what ground are such morbid manifes- 
 tations held to be tubercular? At the present day, the presence of 
 Koch's bacillus seems to be sufficient to affirm the nature of the 
 
UODXJLAR INFECTIONS. 2*\ 
 
 alteration. For some time past, however, histological inve tigatiom 
 have considerably extended the domain of tuberculo i , The 
 criterium is no longer the tubercular corpuscle of Lebert, bul the 
 presence of a gianl cell or a peculiar arrangemenl of various cellfl 
 designated under the name elementary tubercle or tubercular follicle. 
 No doubt the specific character of this lesion i- qo1 absolute, and 
 more or less similar alterations may be encountered where there 
 is no tubercular infection. Nevertheless rnicroscopiste must be 
 credited with having supplied a powerful argumenl in aupporl of 
 the unity of tuberculosis and having included with this di 
 diverse lesions whirl) really belonged therein. 
 
 I [Q 6 
 
 
 
 kCi<^v, 
 
 T^mmPJ. i ' 
 
 Schematic tubercular follicle, showing the three classical zones and the 
 distribution of bacilli. 
 
 Let us, therefore, investigate the constitution of a tubercular 
 follicle, and, to this end, let us suppose an ideal elementary tubercle, 
 ignoring the tissue in which it has developed and the surrounding 
 alterations which it may have produced. 
 
 What peculiarly characterizes the tubercular follicle is not such or 
 such cellular elements, but the mutual arrangement of the various 
 elements of which it is composed. 
 
 Theoretically, according to the conception of Koster, Schuppel, 
 and Friedlaender, the tubercular follicle is formed of three zones 
 (Fig. 6) at the centre, a giant cell, the RiesenzeUe of German 
 authors; around it, epithelioid cells, and at the periphery an area 
 of embrvonal cells. 
 
282 IXFECTIOUS DISEASES. 
 
 The giant cell, held by Schuppel to be characteristic, is composed 
 of a mass of protoplasm containing twenty, or thirty, or more nuclei, 
 situated at the periphery of the cell, where they form a crown or a 
 crescent. The cell itself is rounded, irregular, flat or spherical in 
 shape, often provided with ramified prolongations. The nuclei of 
 the giant cells are commonly oval and nucleolated; in some cases 
 they are elongated and sinuous, or may even present the form of 
 a Z. Finally, when greatly magnified, there may be seen in some 
 of the cells karyokinetic figures in connection with indirect division 
 of the nuclei. The aspect of the nuclei and their arrangement in the 
 form of a peripheral crown enables one to differentiate the tuber- 
 cular giant cell from myeloplaxes and sarcomatous giant cells. 
 
 The middle zone is composed of large epithelioid cells ; the nuclei 
 are rounded or oval, and the protoplasm is abundant and somewhat 
 granular. These cells often contain one, two, or more bacilli; they 
 seem to perish when the parasites become more numerous. 
 
 The peripheral cells are simple embryonal cells, presenting nothing 
 particular. They are very numerous and pressed one against 
 another. They appear in the form of rounded elements, measuring 
 4« to 9,«, and are remarkable for the large size of their nuclei and 
 the scantiness of their protoplasm. In the midst of these cells are 
 found a few fusiform elements which represent a more advanced 
 stage of cellular development. 
 
 The elementary follicle is not always constituted in such a perfect 
 maimer as above described. At the beginning of the process all 
 that is found is a collection of round cells; at a more advanced 
 period the epithelioid cells maybe wanting and the lesion may consist 
 simply of a giant cell surrounded by embryonal elements. 
 
 The tubercle is a non-vascular production. This is a feature of 
 great importance. At the start, while there is nothing but a simple 
 mass of cells, some permeable vessels may yet be found; but subse- 
 quently they become obliterated and disappear; their lumina are 
 occupied by a granular coagulum of fibrin, imprisoning in its meshes 
 white corpuscles accumulated along the inner walls. This vascular 
 obliteration has been variously explained. Some authors have 
 assumed a compression of the vessel (Rindfleisch), others a coagu- 
 lation of the blood (Chauveau) , and still others a primary alteration 
 of the wall — an endocapillaritis (H. Martin). 
 
 About the irritated point the vessels dilate and send out prolonga- 
 tions, which are but short-lived. 
 
NODULA i: INFECTIONS. 
 
 Histogenesis of Tubercle. The method of inv< ligation ; 
 been quite differenl before and since Koch's discovery. During 
 the period thai may be designated as prebacterial, very exacl and 
 detailed descriptions were given of the pathological anatomy of the 
 tubercle. When the specific germ of the di ea e wag known and 
 cultivated it became possible, by inoculating it into animal 
 observe day after day the development of the tubercular neoplasm, 
 without running the risk of regarding accessory and secondary 
 processes as essential, or considering as specific such alterations ae 
 are common to other diseases. 
 
 The importance of lymphatic elements in the genesis and constitu- 
 tion of tubercle was noted from the very beginning of researches. 
 Virchow and his disciples class it with lymphomata. Klebs and 
 Koster think it takes origin in the lymphatic capillary network-. 
 Wagner emphasizes its structural analogy to lymphatic glands 
 (cytogenic tuberculosis). H. Martin and Kiener compare it to the 
 milky patches of (lie omentum. 
 
 Histologists sought for a specific element thai would enable them 
 to distinguish tubercle from similar neoplasms; and such were 
 thought to be the giant cells and the absence of vessels in the tubercle. 
 
 It was not long, however, before new contributions demonstrated 
 that giant and epithelioid cells are in nowise specific. Heidenhain, 
 Weiss, Baumgarten, and Ziegler produced these elements by insert- 
 ing foreign bodies into the subcutaneous cellular tissue. Laulanie 
 observed in the cat granulations which presented the appearance 
 and structure of tubercle and were caused by the strongylus vasorum, 
 Hip. Martin produced pulmonary granulations by intravenous 
 inoculation of inert powders. 
 
 While discussing the diagnostic value of giant and epithelioid 
 cells, the authorities endeavored to discover the mode of formation 
 of these elements. Langhans suggested two possible events: either 
 the giant cell develops at the expense of one altered cell, or is formed 
 by the union and confluence of several. According to Koster, it 
 results from the proliferation of the vascular endothelium : according 
 to Ziegler it develops at the expense of leucocytes, while Shuppel 
 holds it to be due to the hypertrophy of one migrated white corpuscle 
 followed by alterations in the bloodvessels. This vascular origin, 
 while admitted by Cornil, was doubted by Malassez. Charcot and 
 Gombault contended that the giant cell resulted from fusion of 
 manv. 
 
284 INFECTIOUS DISEASES. 
 
 Such were the opinions of authors concerning the histogenesis of 
 tubercle when, in 1882, the discovery of the tubercle bacillus by 
 Koch brought accuracy to our knowledge of tuberculosis. The 
 specific element, which pathological anatomy had failed to furnish, 
 was found out by bacteriology. 
 
 From that moment two principal theories have been advanced. 
 According to some, the tubercular neoplasm is composed solely of 
 cells that pass out of the vessels to ingest the bacilli; the tubercle 
 is a superadded production developing at the expense of protective 
 cells that are attracted toward the point attacked. Others assert 
 that it is formed of the constituent cells of tissues (epithelial cells, 
 fixed cells of connective tissues, vascular endothelium, etc.), and 
 that it is to be attributed to the transformation of pre-existing 
 elements normal to the parts. 
 
 Among the advocates of the former theory is Koch. The bacillus 
 ingested by the wandering cell is transported by it into the organs, 
 and Koch is not far from believing that the same cells give origin to 
 both the epithelioid and giant cells. While Koch hesitates, Metchni- 
 koff is positive. According to the latter authority, the phagocytes 
 pick up and digest the tubercle bacillus. Moreover, the giant and 
 epithelioid cells which he studied in a small rodent, the spermophile, 
 into which he inoculated avian tuberculosis, also have phagocytic 
 properties. The latter statement is contested by a number of 
 authorities. Gilbert and Girode, as well as Yersin subsequently 
 proved that tubercle develops at the expense of wandering cells. 
 Borrel, studying the histogenesis of tubercle in the lung and kidney 
 by means of inoculations of cultures of human tuberculosis, saw the 
 bacilli ingested by polynuclear leucocytes : the latter, however, died 
 rapidly and were replaced by mononuclear leucocytes which in their 
 turn seized upon the bacilli and were transformed into epithelioid 
 and giant cells. Josue, inoculating cultures of human or avian 
 tuberculosis into the bone-marrow of rabbits, discovered the same 
 process and created in this animal lesions which are circumscribed 
 in the case of human and diffuse in that of avian tuberculosis. 
 
 The advocates of the formation of tubercle at the expense of the 
 fixed cells of tissues are also supported by experimental investiga- 
 tions. Baumgarten, who is an enthusiastic defender of this theory, 
 inoculated fragments of tubercular substance into the anterior cham- 
 ber of the eye of a rabbit, and saw the fixed cells divide by karyo- 
 kinesis, giving rise to epithelioid and giant cells. The intervention 
 
NODULA i: TNFECTI0N8. 
 
 of the leucocytes is secondary; they invade the neoplasm already 
 constituted by the elements which originate by indirect division from 
 the pre-existing tissue cells. Tubercle Is formed in all organs in a 
 similar manner. Baumgarten, who reject* phagocyto i thai 
 
 the bacilli are not ingested by the cells. Kostenitch, Vblkow, and 
 Straus are also advocates of the theory of the formation of tubercle 
 
 at I he expense of fixed cells. 
 
 As to the gianl cell, ii is believed by some to I"- formed of one 
 cell. Under the influence of an irritation too weak to bring about 
 
 its division, its nuclei proliferate and remain enclosed in Hie hyper- 
 trophied and undivided protoplasm (Koch, Weigert, Baumgarten). 
 
 Others contend l lint the gianl cell is produced by the coalescence of 
 several cells, or by the penetration of leucocytes into the mass* 
 degenerated protoplasm, or by these two processes simultaneously 
 
 (Arnold, Yersin, Borrel, Kostenitch and Volkow. Josu6). 
 
 We are thus confronted by two theories as to the histogenesi 
 tubercle; both are supported by well-observed experimental : 
 It is therefore to be assumed that both contain some truth and it may 
 then be asked whether they cannot be harmonized. Josue* remarks 
 that, under the name of fixed tissue cells, some have confounded the 
 fixed cells of connective tissue, which certainly play a phagocytic role. 
 and the epithelial cells. In his opinion, the mesodermic cells — the 
 leucocytes, the fixed cells of connective tissue — ingest the bacilli, 
 but the toxins secreted b}^ the microbes may act upon the surround- 
 ing epithelial cells and produce in them epithelioid degeneration. 
 Accordingly, from a histological standpoint, all cells participate in 
 the formation of tubercle ; but as far as the fight against the invading 
 germ is concerned, the principal role devolves upon the mesodermic 
 cells. 
 
 On the arrival of the bacillus, polynuclear leucocytes undertake 
 to ingest it, but they rapidly perish. Then mononuclear leucocytes 
 and connective tissue cells seize upon the germ. Two events are 
 then possible. The organism may immediately triumph, and the 
 tubercle is not produced, or the bacillus maybe victorious, and then 
 two successive phases supervene: in the first, the cells are trans- 
 formed into epithelioid elements and a tubercle is produced : in the 
 second phase, the tubercle undergoes caseous degeneration. Even 
 at this stage of evolution the organism may triumph : if the numerous 
 leucocytes surrounding or penetrating the focus remain powerless, 
 there is another process capable of circumscribing the lesion and of 
 
286 IXFECTIO US DISEASES. 
 
 killing the bacillus imprisoned in the products of its own creation — 
 viz., the process o( sclerosis mvadihg the tubercle. 
 Thus far we have dealt with the local manifestations of the bacillus. 
 
 Its action is not. however, limited to the point at which it comes in 
 contact with the tissue cells, as may be proved by a study of the 
 modifications occurring in the marrow of bones in the absence of all 
 osteomedullary localization. In fact, Josue has recognized that 
 when tubercular lesions exist at any point of the organism a profuse 
 cellular proliferation occurs in the bone marrow. The modifications 
 of this tissue, with reference to the defense of the organism, are 
 equally observed in man and in rabbits which have been inoculated 
 in regions far from bones or subjected to subcutaneous injections 
 of tuberculin. 
 
 Evolution of Tubercle. After having studied the structure and 
 mode of formation of the elementary follicle, it is easy to comprehend 
 the development of granulations, of tubercles properly so called, and 
 of caseous masses. 
 
 Gray granulation is commonly formed of several tubercular fol- 
 licles. Wagner and Charcot admit, in complex follicles, as many 
 simple follicles as there are giant cells. Tubercles, properly so 
 called, which are larger than gray granulations, are essentially made 
 up by the union of several elementary tubercles, but the central part 
 undergoes a modification designated as caseous degeneration. At 
 the periphery are found numerous embryonal cells similar to those 
 observed in the external zone of the follicles. The middle zone is 
 remarkable for the presence of giant cells forming a crown around 
 the central degenerated mass. This agglomeration, therefore, pos- 
 sesses a certain individuality. It does not represent, juxtaposed, 
 independent follicles each undergoing degeneration; we are in the 
 presence of a true pathological unity the centre of which degen- 
 erates. 
 
 The foregoing statement with regard to tubercle may be applied 
 to tubercular infiltration, which is characterized by confluent granu- 
 lations connected by means of embryonal cells. According as the 
 mass is made up of granulations or of caseous tubercles, the condition 
 is known as gray or yellow infiltration. As Prof. Grancher states, 
 every tubercle is composed of two zones — a central caseous zone and 
 a peripheral embryonal one. A closer study of the evolution of the 
 lesions shows that a tubercle is liable to two forms of degeneration 
 — fibrous and caseous. 
 
NODULAR INFECTIONS. 
 
 Caseification is preceded by a Btage which Prof. Grancher di 
 aates as vitreous degeneration: the giant and epithelioid cell lose their 
 nuclei, become vitreous, homogeneou , and coale <■<•: thm a translu- 
 cent mass is formed with fii lire imparting to ii the appearance of 
 an irregular mosaic. This peculiar substance look omewhal like 
 amyloid substance, bu1 does nol manifest ite reactions. The trans* 
 lucent mass soon becomes opaque. This is caseous transformation, 
 in which cellular elements are no longer recognizable; the bacilli 
 to share the fate of the animal cells; there are very few of them to 
 be found. This caseous transformation, which has long been 
 
 regarded as specific, may be wanting i an and particularly in 
 
 animals. On the other hand, LI may be encountered in various 
 other pathological conditions, notably in syphilis. 
 
 The caseous mass softens, especially when it is communicating 
 with the exterior; it may undergo a purulenl transformation, result- 
 ing from contamination by pyogenic bacteria. 
 
 In other instances the tubercle undergoes a fibroin metamor- 
 phosis; this is a tendency toward recovery. Tubercle is transformed 
 into a hard nodule composed of a homogeneous fibrous tissue, includ- 
 ing a few atrophied round cells. Vessels develop in the embryonal 
 zone in which giant cells are still found. At certain points the 
 caseous substance becomes encysted ; at times it is absorbed. Finally, 
 tubercle may become infiltrated with calcareous salts and undergo 
 pigmentary transformation. 
 
 Action of Tubercular Toxins. The tubercle bacillus is capable not 
 only of producing tubercles, but it may likewise produce fatty, hyaline 
 and amyloid degenerations. The sclerotic process which it excites 
 may become preponderant, leading to cirrhoses, especially appre- 
 ciable in the liver, and it may be encountered in other parts of the 
 organism; the author has shown its occurrence in the muscles, and 
 Dr. Tessier has proved its importance in connection with the heart. 
 
 The phenomena of degeneration seem to be due to secretory prod- 
 ucts of the microbes (Maffucci, Grancher). As to the tubercles, they 
 are produced by a reaction of the system against the bacillus — i. c 
 the substances contained in the body of the bacillus. The interven- 
 tion of the living micro-organism is not necessary. The experiments 
 of Prudden and Hodenpyle, Straus, Gamaleia, and Vissman demon- 
 strate that injection of thick emulsions of dead cultures of tubercle 
 bacilli into the veins of animals may produce extremely numerous 
 granulations containing; dead bacilli which can be stained bv the 
 
288 INFECTIOUS DISEASES. 
 
 usual methods. This necrotuberculosis, to use an expression em- 
 ployed by Drs. Grancher and Ledoux-Lebard, is characterized by 
 considerable emaciation and a cachexia ending in death. The 
 necropsy reveals tubercular granulations, particularly abundant in 
 the lungs and remarkable for their tendency to undergo fibrous 
 transformation and for the absence of caseation. Straus and Gama- 
 leia. however, have seen the* centre of such tubercles become caseous, 
 as under the influence of living bacilli. Schweinitz and Dorset 
 admit that the necrosing substance is a definite body having the 
 formula C 7 H 10 O 4 , and that it is found in culture fluids. The bodies 
 of the bacilli contain an albuminoid substance which is antagonistic 
 to the preceding one; it produces hyperthermia, while the other 
 lowers the temperature, and it is sclerogenic instead of being necro- 
 genic. 
 
 A series of experiments pursued by the author demonstrate that 
 special toxic substances are contained in the tubercular tissue itself. 
 In most cases he employed extracts of tubercular glands of cattle 
 and dogs or the liver of tubercular guinea-pigs, either pure or mixed 
 with substances capable of modifying their action. It was thus 
 learned that tubercular tissues contain substances more noxious for 
 the rabbit than the guinea-pig. The emaciation caused in the rabbit 
 is more pronounced and lasts longer. 
 
 Inoculability of Tuberculosis. There is hardly a mammalian alto- 
 gether refractory to tuberculosis. Nearly all may contract it spon- 
 taneously or by inoculation. In laboratories the animals most oper- 
 ated upon are the rabbit and the guinea-pig. With the latter animal 
 inoculation is successful, no matter by what route the material is 
 introduced — whether into the subcutaneous cellular tissue, the 
 pleura, the peritoneum, or the anterior chamber of the eye. 
 
 As in the case of other infections, the number of bacilli introduced 
 must be taken into account : the greater the amount of virus intro- 
 duced the more rapidly the disease develops. 
 
 The researches of Bollinger and Gebharclt demonstrate that dilu- 
 tion of tubercular substances may render them inoffensive: con- 
 taminated milk loses its virulence if diluted to T \-$ or y^-. Animals 
 resist when they swallow 2 c.cm. of tubercular sputum diluted to \. 
 If, however, inoculation is made beneath the skin or into the peri- 
 toneum, it must be diluted to t o 0*000 m or der to become inoffensive. 
 
 Hischberger, Gebharclt, and Wissokowicz have also demonstrated 
 that rabbits resist amounts which are fatal for guinea-pigs; in the 
 
NODULAR INFECTIONS. 288 
 
 latter animals tuberculosis developi when a particle ol putum con- 
 taining 820 bacilli is inoculated. Upon this fad Wissokowicz b 
 his explanation of the re nil obtained by inoculating ubstance* 
 taken from local tuberculosis in man. The reason why, in this 
 instance, rabbits resisl while guinea-pigs succumb is, according to 
 this author, not the attenuation of the virus bul its dilution; the 
 number of bacilli is too small to overcome the resistance of the 
 rabbits. Dr. Arloing objects to the assertion thai a certain number 
 of rabbits or guinea-pigs may become diseased by the injection of 
 diluted bacilli; if, however, the virus is subjected to a temperature 
 of 110° F. (t)0° C.) for fifteen, thirty, or sixty minutes, it becomes 
 attenuated, and the bacilli are then no longer able to kill the rabbit, 
 though I hey still render guinea-pigs tuberculous by acting upon these 
 animals like the scrol'ular virus: the latter virus, therefore, repr< 
 an attenuated tubercular virus, a more or less fixed rare f Koch's 
 bacillus. 
 
 Tuberculosis of Animals. Among the animals mosl susceptible to 
 the spontaneous development of tuberculosis the bovidse must firsl be 
 mentioned. The frequency of bovine tuberculosis varies according 
 to races and countries. While rare in polar countries, tuberculosis 
 is especially prevalent in hot countries, notably in Italy, where it 
 presents the characters of a veritable scourge. Even in those 
 countries in which tuberculosis is most frequent, it is exceptional 
 in young animals ; the average for calves is below 1 per 10.000. 
 
 The tubercular infection is in some cases expressed by a general 
 malady affecting the serous membranes and resembling human mil- 
 iary tuberculosis; in other instances, by pulmonary or abdominal 
 lesions; lastly, the bacilli may become localized at a certain point 
 and give rise to local tuberculosis. Pulmonary tuberculosis is 
 undoubtedly the most common form of the disease. 
 
 The frequency of mammary tuberculosis has been the subject of 
 much controversy. In less than a year Bang observed seven cases 
 in Copenhagen. In France it seems to be of rare occurrence, and 
 danger of contamination through milk seems to be not so great as 
 Mas once believed. 
 
 Observations upon tuberculosis in the horse are not very numerous. 
 The lesions are sometimes limited to the organs of the abdominal 
 cavity, occupying the viscera and glands: sometimes they are found 
 only in the lungs, and in some instances they are generalized. 
 
 Tuberculosis in swine varies according to the countries from 0.1 
 
 19 
 
•290 [XFECTIO US Disj;. I SKS. 
 
 to 1 per 1000. These estimates, coming from the abattoirs, are 
 probably below the real figures, since the diseased animals grow 
 rapidly thin, and are, therefore clandestinely killed and sold. 
 
 Contrary to the assertions of some authorities, tuberculosis in 
 the goat and sheep is not exceptional. Moreover, experimentation 
 proves that the goat can be rendered tubercular the same as other 
 animals. 
 
 The remarkable researches of Cadiot 1 have established that tuber- 
 culosis is very frequent in the dog. The contrary opinion is due to 
 the fact that, in this animal, the lesions often appear in the form of 
 neoplastic productions, although, in some instances, they are similar 
 to those commonly observed in man— 1 e., pulmonary cavities and 
 alterations in the urinary apparatus. 
 
 In the cat, as in the dog, tuberculosis may be generalized or 
 limited to the organs of the thorax and abdomen. Voluminous 
 mesenteric adenopathies are commonly present, indicating that the 
 virus has entered through the intestine. 
 
 According to the statistics of the London Zoological Gardens, 
 monkeys become tubercular in the proportion of 15 per cent. The 
 infection invades particularly the lungs and the liver, subsequently 
 involving the kidneys, the spleen, and less frequently the intestine. 
 Contrary to what was formerly believed, rabbits and guinea-pigs, 
 which are so frequently employed for experimental purposes, are 
 seldom, if ever, spontaneously affected by this disease. The so-called 
 spontaneous tubercles are clue to cysticercus, coccidia, or to microbes 
 other than Koch's bacillus. 
 
 Tuberculosis of the Gallinae. Tuberculosis of the gallime was 
 identified with that of the mammalia when Koch, Ribbert, Babes, 
 Cornil, and Megnin demonstrated the presence in them of bacilli pre- 
 senting the same coloring reactions as the bacillus of the mammalia. 
 Soon afterward Drs. Nocard and Roux cultivated the avian bacillus, 
 and their cultures were employed in all the laboratories of France 
 for experimental purposes. The identity of avian and mammalian 
 tuberculoses was accepted without much controvers3 r , since experi- 
 mentation demonstrated that avian tuberculosis could be inoculated 
 into rabbits, and several observations seemed to point to the trans- 
 missibility of human tuberculosis to birds. 
 
 It was not long, however, before negative results were reported: 
 
 1 Cadiot. Tuberculose du chien, Paris, 1892, vol. i. 
 
MODULAR INFECTIONS. 291 
 
 Straus and Wurtz 1 caused chickens and a cock to swallow human 
 tubercular sputa for from six to twelve month ; the animal* re i 
 and the necropsies demonstrated the complete integrity of their 
 organs. Maffucci also demonstrated thai mammalian tuberculosis 
 was not transmit ted to the gallime; I wenty chickens were inoculated 
 subcutaneously, by the stomach, lungs, peritoneum, and vein . and 
 :ill resisted. 
 
 The unity of tuberculosis in the various animal species wae thus 
 rendered questionable. This doubl wassharedby Koch,who,a1 the 
 Congress in Berlin, declared he had resumed the study of the question 
 and could tio longer completely identify the tuberculosis of birds and 
 of the mammalia. From thai momenl a series of contributions 
 appeared which clearly demonstrated the differential characters of 
 the two forms of tuberculosis. Mention may be made of the numer- 
 ous investigations which the author pursued with Drs. Cadiol and 
 Gilbert, 2 (hose of Straus and Gamaleia, 3 and of Courmonl and Dor/ 
 
 The fundamental fact demonstrated by these experiments is one of 
 general pathology — i. e., that tuberculosis may be transmitted from 
 one species to another, but its evolution is directed by the infected 
 organism itself. It is the eternal question of the seed and soil. The 
 hepatic tubercles of the chicken and of the pheasant, for instance, 
 are not only distinguished from the hepatic tubercules of the mam- 
 malia, but they are highly differentiated among themselves, although 
 developing in so closely allied animal species. This fact cannot be 
 too strongly emphasized, since it strikingly shows the pathological 
 particularism of animals and indicates the great error of hastily 
 generalizing conclusions drawn from experiments made upon a single 
 animal species. 
 
 Comparison of the Tuberculoses of the Mammalia and the Gal- 
 linae. There are certainly numerous differences between the virus 
 
 1 Straus and Wurtz. Sur la resistance des poules a la tuberculoso par ingestion. 
 Congrea pour l'etude de la tuberculose, 18SS. 
 
 ; Cadiot, Gilbert, and Roger. Note sur la tuberculose des volailles. Soc. de biologie, 
 Oct. 11, 1890. Xote sur l'anatomie pathologique de la tuberculose du foie chez la poulo 
 et le faisan, ibid., Oct. IS, 1S90. Inoculation aux gallinaces de la tuberculose des 
 mammiferes, ibid., July 2.5, 1891. Inoculabilite* de la tuberculose des gallinaces aux 
 mammiferes, ibid., Feb. S. 1S96. Unieite des tuberculoses humaine et aviaire. ibid.. 
 Feb. S, 1896. Sur un precede permettant de transmettre la tuberculose des maniniiferes 
 aux gallinaces, ibid., Nov. 19. 1S9S. 
 
 3 Straus and Gamaleia. Recherches experimentales sur la tuberculose. Arch, de 
 medecine expeximentale, 1891. Straus. La tuberculose et son bacille. Pari*. 1S95. 
 
 4 Courmont and Dor. Tuberculose aviaire et tuberculose des mammiferes. Oongtvs 
 pour l'etude de la tuberculose, 1S91. 
 
292 TXFECTIO US DISK. I s]-;s. 
 
 of the mammalia and that of gallinse. The avian bacilli are longer 
 and more granular. They develop more readily in artificial culture 
 media and multiply at once in glycerinated agar-agar, while the 
 bacilli of human tuberculosis cannot vegetate in this medium except 
 after having been several times cultivated in serum. The avian 
 bacillus vegetates at 109.4° F. (43° C.) and resists a temperature of 
 149° F. (65° C.)i the human tubercle bacillus ceases to develop at 
 105.8° F. (41° C.) and dies at 149° F. (65° C). An avian culture 
 ten months old is living and can yet be sown ; a human culture loses 
 its capacity to vegetate in six months (Maffucci). Avian tuber- 
 culosis may be transmitted to chickens; it seldom, if ever, causes 
 generalized tuberculosis in guinea-pigs, and, except in certain rare 
 instances (observation of Richet and Hericourt), it cannot be in- 
 oculated into the dog. Human tuberculosis is but exceptionally 
 transmitted to chickens; it almost invariably gives rise to gener- 
 alized tuberculosis in guinea-pigs, and is easily inoculated into the 
 dog. 
 
 Such are the differences existing between the two viruses, and all 
 are of secondary importance, which does not warrant their being con- 
 sidered as two different species. The general features of the two 
 bacilli are the same, and the reactions which they arouse in the living 
 organism are similar. The morphological differences are likewise of 
 a secondary order. Differences no less notable are observed when 
 tubercular bacilli present in various individuals of the same species 
 are compared with each other. It is not rare to find in man some 
 bacilli longer and more granular than others. 
 
 Agreement is universal as to the identity of the soluble products, 
 notably tuberculin, whatever their origin may be. 
 
 These facts point to the conclusion that the two tubercular bacilli 
 represent two varieties of the same species. There are undoubtedly 
 marked differences between the two varieties, and it is impossible 
 to apply to one the results obtained with the other; hence, in order 
 to avoid confusion, it is always necessary to indicate the virus em- 
 ployed. Nevertheless, in conjunction with distinctive characters of 
 importance, we find a common basis warranting the belief that these 
 two pathogenic agents are derived from the same species: unity 
 of tuberculosis of the mammalia and of gallinae; such seems to us 
 the conclusion suggested by the ensemble of facts thus far observed, 
 which will now find fresh support in the researches pursued by us 
 upon tuberculosis of psittaci. 
 
NODULAR INFECTIONS. 
 
 293 
 
 Tuberculosis of Psittaci. 
 
 Frohner and bis assistant, Eberlein, were the first to draw atten- 
 tion to the frequency of tuberculosis in parrots and to show thai 
 the disease commonly involved the skin, mucous membranes, sub- 
 cutaneous and submucous connective tissue, the articulations, and 
 hones. Of 700 parrots broughl to the clinics of the Berlin School, 
 170 were tubercular say 25 per cent. 
 
 The cases studied by the author with Drs. Cadiol and Gilb 
 were 27 in number. Of these, L5 were tuberculosis of the -kin. \) 
 of the mucous membranes, 6 boil i of (Ik- skin and mucous membranes. 
 The lesions are in the greal majority of cases aboul the head. Pig. 7) 
 
 Fig. 7. 
 
 
 Tuberculosis of the parrot. 
 
 Iii the majority of our observations the lesions presented such a 
 peculiar appearance that their nature could not be recognized before 
 the employment of bacteriological measures. The cutaneous mani- 
 festations differ altogether from those observed in other animals; 
 they may be compared only to certain forms of lupus verruc - 
 There first occurs a shedding of the plumage : then the skin thickens 
 and becomes verrucous, and vegetations soon appear which become 
 covered with thick crusts. If these be detached a granular tissue 
 is exposed. Ulcerations are not uncommon, and are produced i - - 
 
 1 Cadiot, Gilbert, and Roger. Inoculabilitc de la tuberculose des manimiferes aux 
 psittaces. Soc. de biologie, December 14. 1S95. La tuberculose des perroquets. ses rap- 
 ports avec la tuberculose humaine. La presse medicale, January 26, 1896. 
 
294 I NFEi ■ TIO US DISEA SES. 
 
 dally when the diseased parts are exposed to traumatism or repeated 
 friction. In certain instances the lesion occupies the subcutaneous 
 
 tissue; it is a tumor of fibrous consistency which may attain the size 
 of a cherry. Later on the centre softens and is transformed into a 
 caseous mass.' 
 
 Finally, there is a very peculiar localization which has given rise 
 to many diagnostic errors. The author refers to the tubercles devel- 
 oping near the claws, which become deformed and crooked absolutely 
 as in the cases described under the name of gout of birds. 1 
 
 Visceral manifestations with or without other lesions may occur 
 — gastroenteritis marked by diarrhea, and pulmonary tuberculosis 
 attended by a troublesome and frequent cough. 
 
 As parrots live with man and have hardly any communication 
 with other animals, it is reasonable to assume that their tuberculosis 
 is of human origin. That is precisely what observations prove. In 
 a fair proportion of the cases observed by us the tubercular parrots 
 belonged to emaciated individuals with chronic cough, the nature of 
 the affection proving to be tubercular in certain cases which we sub- 
 mitted to bacteriological examination. 
 
 "Without dwelling upon the inoculability of tuberculosis of both 
 mammalia and gallina? into the psittaci, as our experiments fully 
 demonstrated, we may say, in conclusion, that the results obtained 
 with the avian virus are altogether comparable to those furnished 
 with the human virus. The parrot, among birds, behaves as does 
 the rabbit among mammalia. These are two animals equally sensi- 
 tive to the two varieties of tuberculosis. 
 
 Having briefly presented the features of human and avian tuber- 
 culosis, we may conclude that the various bacilli encountered in man, 
 mammalia, and birds are no more than varieties of one and the same 
 species. It is necessary to admit two principal varieties: one, desig- 
 nated as human, attacks man, mammalia, and, among the birds, the 
 psittaci; the other, improperly called avian, is observed in the gallim~e 
 and sparrows. Numerous facts demonstrate that it is possible, 
 although difficult, to cause each of these two bacilli to lose its so- 
 called specific properties, which means that these properties are not 
 truly specific, since the term species implies fixed virus, not suscept- 
 ible to transformation. Therefore, in spite of the differential char- 
 acters of the two great varieties of tuberculosis, we conclude that the 
 disease is one. 
 
 1 Larcher. Melanges de pathologie comparee et de t6ratologie. Paris, 1878, p. 153. 
 
NODULAR INFECTIONS. 295 
 
 Our view, which is likewise thai of Drs. Arloing, Nocard, Cour- 
 mont, Dor, and others, leads to eonclu ion of practical importance. 
 Since tuberculosis may develop in man through the agency of the 
 avian bacillus (Kruse), tubercular birds, and notably certain d 
 prepared with their viscera, should be excluded ae food. 
 
 The dangers of contamination are greater when parrots are con- 
 cerned. In these birds the bacilli acquire extraordinary virulena 
 for certain mammalia, as was demonstrated by our inoculations made 
 into guinea-pigs; human t uberculosis is seldom so active upon these 
 small rodents. The bacilli of the diseased parrol are found in the 
 cutaneous productions, saliva, nasal mucus, and a1 times in the 
 excrements; they may easily be disseminated. Parrots contamin- 
 ated by man thus become in their I urn a permanent focus of tuber- 
 cular infection. 
 
 Pseudotuberculoses. 
 
 The expression pseudotuberculosis is applied to a series of very 
 
 dissimilar lesions having no other common character than the pres- 
 ence of small tumors, the macroscopic appearance of which resembles 
 
 that of tubercle; in other words, this group includes all those i 
 in which the granular lesions are not dependent upon Koch's bacillus. 
 It would be logical to include in the group glanders and certain 
 cases of miliary pyemia. We retain the expression because it is 
 generally employed. It is advisable, however, to render its meaning 
 clear by an epithet specifying the kind of pseudotuberculosis con- 
 cerned. In fact, of the latter there are numerous varieties, which 
 may be divided into four groups: 
 
 Pseudotuberculoses by inanimate substances. 
 
 Pseudotuberculoses by animal parasites. 
 
 Mycotic pseudotuberculoses. 
 
 Bacterial pseudotuberculoses. 
 Pseudotuberculoses by Inanimate Substances. At the time when 
 experimenters were endeavoring to refute Villemin's doctrine it was 
 asserted that any substance introduced into the veins or peritoneum 
 brings about the production of tubercles. These were said to be 
 obtained by injecting pus. putrefied muscle, tissue fragments, and 
 inorganic substances. All the results seemed to be in harmony, from 
 the researches of Lebert and Wyss down to those of Cohnheim and 
 Fraenkel, who subsequently changed their opinion and recognized 
 the specific nature of tubercles. 
 
296 IXFECTIOUS DISEASES. 
 
 A good many causes of error had crept into the experiments. 
 .Miliary abscesses, infarctions, granulations produced by inert sub- 
 stances, had all been mistaken for tubercular lesions. These granula- 
 tions have been well studied by H. Martin, 1 who has described three 
 principal varieties: the powder of cantharides produces nodules com- 
 posed of embryonal cells; with lycopodium the lesion is characterized 
 by giant cells surrounded by round elements; finally, Cayenne pepper 
 induces the formation of true follicles composed of three zones such 
 as are observed in tuberculosis. Since histology was not capable of 
 differentiating these diverse granulations, resort was to be had to 
 experimentation. Dr. Martin showed the pseudotubercles to be 
 devoid of infectious properties. Their inoculation into another animal 
 produced no lesion, or only a few granulations which were no longer 
 inoculable. On the other hand, true tubercle is inoculable in series, 
 and may be transmitted indefinitely from animal to animal. 
 
 Analogous productions have been observed in man. Drs. Cornil 
 and Toupet described a cutaneous tubercle composed of follicles, but 
 which contained no bacilli. Careful examination revealed in the 
 centre of the neoplasm the presence of small fragments of 03^ster-shells 
 around which the lesion had developed. Hanan's observation is no 
 less interesting. At the necropsy of an individual who died thirteen 
 da} T s after perforation of a round ulcer, Hanan found numerous 
 miliary granulations in the parietal peritoneum and in the adhesions 
 which had formed between the liver, diaphragm, and duodenum. 
 These granulations had the structure of non-caseous tubercles ; they 
 contained no bacilli, but hard, stony tissue cells of pears. 
 
 Pseudotuberculoses by Animal Parasites. Pseudotuberculoses 
 by animal parasites have but exceptionally been observed in man. 
 These are small, yellow, pale, or greenish tubercles varying from a 
 hempseed to a hazel-nut in size. 
 
 Among the principal pseudotuberculoses caused by parasites may 
 be mentioned that of the cat, produced by the ollulanus tricuspis 
 (Leuckart) ; that of the sheep, called also verminous pneumonia and 
 due to the pseudalius ovis pulmonalis (Koch), and that of the calf, 
 dependent upon the strongylus rufescens. These pseudotubercu- 
 loses are histologically characterized by simple agglomerations of 
 embryonal cells, and are, therefore, allied to glanders rather than to 
 tuberculosis. Such is not the case with the verminous tuberculosis 
 
 1 H. Martin. Tuberculose des sdrenses et du poumon. Pseudotuberculose expdri- 
 mentale. Archives de physiologie, 1880. 
 
so I) i I, ! // INFECTIONS. 297 
 
 of the dog, produced by the strongylus vasorum and well studied by 
 Dr. LaulanieV This observer showed thai the ova of strongylu 
 arrested in the ramifications of Mm- pulmonary artery and induce 
 cellular proliferation within or around ili (i vessel . In the former 
 instance, at the centre of the neoplasm is ton ml a giant cell containing 
 an ovum or an embryo surrounded by epithelioid or embryonal cells ; 
 in the latter case, when the tubercles are formed around the v< 
 the artery undergoes aneurysmal dilatation and is surrounded by a 
 zone of gianl and epithelioidal cells. 
 
 Mycotic Pseudotuberculoses. Plants of a relatively higher or- 
 ganism may cause the development of granulations more or less 
 similar to those of tuberculosis. We shall first cite the streptoti 
 or oospora, which constitute a transition between bacteria and fungi. 
 The interest attached to this group is the more considerable, since, 
 as has already been stated, the agent of true tuberculosis, Koch's 
 bacillus, is at the present held to be rather a streptothrix. Moreover, 
 the. disease most closely allied to tuberculosis, actinomycosis, is due 
 to a fungus which botanists agree should be classed with the - 
 family. 
 
 Among other pathogenic streptothrixse there is one which i- the 
 agent of the disease improperly called farcin of cattle {farcin du 
 b(vuf); this agent, discovered by Nocard, who considered it a 
 cladothrix, is at present known under the designations streptothrix 
 oospora, nocardia farcinosa. 
 
 The aspergillus deserves a more careful study. The aspergillus 
 glaucus and fumigatus produce in animals granulations with giant 
 cells, at the centre of which is found the parasite. These facts, well 
 studied experimentally by Kaufmann and Lichtheim, were com- 
 pleted by the interesting investigations of Dieulafoy, Chanter;, ss 
 and Widal, Potain, Gaucher, Sergent, and Renon. These authors 
 described a peculiar disease observed in men whose work compels 
 them to handle grain or flour contaminated with the spores of the 
 aspergillus fumigatus. The disease is ushered in as ordinary tuber- 
 culosis, by cough, hemoptysis, and a greenish expectoration. The 
 sufferer loses flesh and presents some fever toward evening. Auscul- 
 tation reveals bronchitic rales and blowing respiration, and at times 
 signs of pleurisy. In other cases the beginning is announced by 
 bronchitis and an asthma-like dyspnea which grows worse at night. 
 
 1 Laulanio. Sur quelques affections parasitaires du poumon et leur rapport avec la 
 tuber culose. Archives de physiologie. iss-j. 
 
298 INFEl ■ Tl < > ( rs DISEASES. 
 
 When the disease is uncomplicated, recovery is the rule after a 
 series of ameliorations and aggravations lasting from three to eight 
 
 years. Quite often, however, aspergillosis coexists with true tuber- 
 culosis, and the latter is responsible for the graver incidents and fatal 
 termination. 
 
 The diagnosis cannot be reached otherwise than by microscopic 
 examination of the sputa and by cultures and inoculations. By 
 employing the fluid of Jaulin cultures may be obtained within 
 forty-eight hours. The intravenous injection of sporulated culture 
 kills pigeons in three or four days, guinea-pigs in four or five days, 
 rabbits in six or eight days. 
 
 Bacterial Pseudotuberculoses. The great discovery of Koch 
 seemed to permanently demonstrate the unity of tuberculosis. The 
 fact that Toussaint had, in 1880, described a micrococcus found in a 
 tubercular cow was soon forgotten. Although the author succeeded 
 in cultivating the microbe and reproducing the disease in cats, the 
 results were supposed to be due to error, and no attention was given 
 to them. It was, therefore, with a mingled feeling of surprise and 
 incredulity that, in 1883, the profession received from Malassez and 
 A ignal 1 the description of a tuberculosis due to a parasite other than 
 Koch's bacillus. By inoculating a subcutaneous tubercle, taken 
 from a child dead of meningitis, these experimenters produced a 
 disease transmissible in series and apparently due to colonies of 
 zooglea? which could be seen at the centre of the tubercular nodules. 
 However, the fact that, in continuing their investigations, these gen- 
 tlemen noticed the gradual decrease of the zooglese in successive pas- 
 sages, brought doubt upon the individual^ of the infection. Finalty, 
 they were replaced by bacilli identical with Koch's. Had an acci- 
 dental contamination occurred, as was first believed, or a true trans- 
 formation, as the researches of Bataillon and Terre tended to show? 
 According to the latter hypothesis, zoogleic tuberculosis would be 
 only a form of true tuberculosis. 
 
 Zoogleic tuberculosis was found by various authorities. Castro- 
 Sofia found the zooglese in an osseous abscess of the instep. Eberth 
 encountered them in a guinea-pig and a rabbit ; Nocard in a chicken ; 
 Manfredi induced a zoogleic tuberculosis by introducing into the 
 abdominal cavities of guinea-pigs fragments of cotton through which 
 
 1 Malassez and Vignal. Tuberculose zoogl6ique. Archives de physiologie, 1S83. Sur 
 le mieroorganisme de la tuberculose zoogleique. Ibid., 1884. 
 
NODULAR INFECTIONS. 
 
 299 
 
 he bad filtered the air of a hospital ward where tubercular patient* 
 breathed. Other observations were reported by Grancher, 1/ 
 Pfeiffer, and ol hers. 
 
 The authors who firsl undertook i he si udy of zoogli ic tuberculosis 
 commonly contented themselves with microscopic examinations; the 
 attempts at culture made by them were insufficient to enable them 
 to specify the disease. Having the occasion to observes pseudo- 
 tuberculosis develop spontaneously in ;i guinea-pig, viz., withoul any 
 inoculation, we endeavored to study the disease more thoroughly. 1 
 
 We easily obtained pure cultures of the pathogenic agenl and 
 induced the affection in various animal species. Though the lesion 
 
 Fig. 8. 
 
 Bacillary pseudotuberculosis. Hepatic granulations with central cells strongly 
 stained. X 150. 
 
 appeared similar to tubercles when the organs were examined with 
 the unassisted eye. histological examination demonstrated that the 
 granulations differed considerably from true tuberculosis and from 
 zoogleic tuberculosis. 
 
 The lesion is of extreme simplicity I Fig. 8) ; it is a collection of 
 round or epithelioid cells with large nuclei. Xo where is degeneration 
 observable; the central part is most deeply stained. On the other 
 
 1 Charrin and Roger. Xote sur une pseudotuberculose bacillaire. Soc. de biologie 
 and Academic des science. 1888. Roger. Tuberculose et pseudotuberculose. G 
 hebdomadaire, 1S90. 
 
:M,> 
 
 / XFK ( ■ Tl I S DISK. 1 N ES. 
 
 hand, in zoogleic tuberculosis the centre of the nodules appears like 
 a granular zone I Fig. 9), and in this zone the parasite accumulates 
 in the form of zooglese. In view of the difference in their histological 
 features, we admitted that zoogleic tuberculosis and bacillary pseudo- 
 tuberculosis represent two distinct affections. Such was also the 
 (•pinion of Dr. Malassez. 
 
 .More recently, however, zoogleic tuberculosis was again studied 
 by Drs. Grancher and Ledoux-Lebard, 1 Nocard, and Masselin, as well 
 as Zagari; these authors accurately indicated the characters of the 
 cultures and held our disease to be identical with that of Malassez 
 and Vignal. We believe that the histological study invalidates this 
 opinion, and think that these affections are two different diseases, 
 in spite of their man} 7 points of resemblance. 
 
 Fig. 9. 
 
 '' : ^d&P£/ : '^J^.M 
 
 Zoogleic tuberculosis. Hepatic granulations presenting three zoogleic masses of 
 a caseous aspect and fragments of hepatic trabecular X 100. 
 
 Close to these pseudotuberculoses are: the experimental syphilis 
 of Disse and Taguchi, the pseudotuberculosis observed in the guinea- 
 pig by Morat and Doyon, Bonome, and Cipollina; the pseudotuber- 
 culosis engendered by the inoculation of substances suspected to be 
 anthrax (Zagari) or the injection of milk (Parietti) ; the pseudotuber- 
 culosis spontaneously appearing in the antelope (Cornil and Toupet), 
 and in the hare (Megnin and Mosny). 
 
 1 Grancher and Ledoux-Lebard. Recherches sur la tuberculose zoogl6ique. Archives 
 de m£decine experimentale, 1889 and 1890. 
 
NODULAR INFECTIONS. 30] 
 
 Human Pseudotuberculoses. The study of bacterial pseudotuber- 
 culoses is rendered highly interesting by the fad thai they occur in 
 man, as is proved by the researchei of Mala* ez and Vignal ' 
 Sofia, Babes, and Masselin. Some recenl observations tend to 
 that they are nol of uncommon occurrence. 
 
 Drs. Du C.'i/.'il and Vail lard 1 made a necropsy upon the cadaver of 
 a man who rapidly succumbed to an infect inn characterized by f< 
 diarrhea, and abdominal pains. The peritoneum and pancreae were 
 found to be the seal of ;in erupl ion of caseous nodules. These lesions 
 contained a large bacillus, which was cultivated and proved to I"- a 
 facultative anaerobic, liquefying gelatin and imparting to the cultures 
 the odor of ammonia. Its subcutaneous inoculation reproduced the 
 disease in the rabbit, and its intravenous injection gave rise, accord- 
 ing to the dose, to granulations or a septicemia. The guinea-pig 
 appeared refractory. 
 
 A short time after this publication, Dr. Legrain 2 described a similar 
 bacillus which was associated with Koch's bacillus in the sputa of a 
 consumptive. Then came the investigations of Bayem and Les a 
 who, in a case of tuberculosis of the suprarenal capsules, found a 
 bacillus analogous to if not identical with the one characterizing our 
 bacillary pseudotuberculosis. In pursuing the study of this microbe, 
 Lesage learned that it closety resembled the bacillus coli communis. 
 
 We must likewise refer to those cases of acute miliary tuberculosis 
 in which Koch's bacillus has not been found. Such are the facts 
 reported by Kouskow, Charrin, and J. Courmont. In the two cases 
 published by Courmont the individuals were the offspring of tuber- 
 cular parents ; the inoculation of their pulmonary lesions into guinea- 
 pigs gave rise to a rapid, atypical tuberculosis. 
 
 Thus far, cases of pseudotuberculosis have been encountered in 
 man twelve times, ten times in the rabbit and guinea-pig, twice in 
 cattle and sheep, once in the cow, the antelope, the hare, and the 
 chicken. The microbes must be widely distributed in the soil, as is 
 indicated by their frequent occurrence in small rodents — guinea-pigs 
 and particularly in rabbits — in which animals the disease, the mode 
 of entrance of which is sufficiently evidenced by intestinal lesion-, 
 at times prevails in the form of an epizooty. 
 
 1 Du Cazal and Vaillard. Sur une mala die parasitaire de l'homme transmissible au 
 lapin. Annates de l'lnstitut Pasteur, 1S91. 
 
 : Legrain. Sur une pseudotuberculose produite par un baoille trouve chez un phtisique. 
 Bulletin medical. 1S91. 
 
302 INFECTIOUS DISEASES. 
 
 By collecting the observations thus far published we reach the 
 following classification: 
 
 Micrococcic tuberculosis of the row (Toussaint, 1880). 
 Zo6sl< ie tuberculosis (Malassez and Vignal, 1SS3). 
 Bacillary pseudotuberculosis (Charrin and Rojjer. lssxi. 
 Pseudotuberculosis (probably zoogkic) 
 
 of the guinea-pig (Zagari, Bonome, Cipellina). 
 
 of the rabbit (Dor: streptobacillary). 
 
 of the hare (Megnin and Mosny). 
 
 of the antelope (Connl and Toupi I i. 
 Fetid bacillary pseudotuberculosis (Parietti). 
 Pseudotuberculosis of the mouse (Kutscher, Galli-Valerio). 
 Bacillary pseudotuberculosis of the sheep (Preisz and Guinard). 
 Bacillary pseudotuberculosis of the hog (Galli-Val6rio) . 
 Human bacillary pseudotuberculosis 
 
 of Du Cazal and Vaillard. 
 
 of Hayem and Lesage. 
 
 of J. Courmont. 
 
 of P. Courmont. 
 
 Oidiomycosis or Endomycosis. 
 
 We have repeatedly stated that infectious diseases are character- 
 ized by their clinical evolution and not by the nature of the causative 
 agent. This conception led us to class with infections certain pro- 
 cesses dependent upon non-bacterial parasites — plants or even 
 protozoa. The study of the experimental disease which is caused 
 by intravenous inoculation of oiclium albicans will, we believe, 
 corroborate our argument. Its history represents for us the type 
 of a non-bacterial infection. 
 
 Biology of the Parasite. It is not necessary here to speak at 
 length of the morphological and biological characters of oiclium; 
 their description will be found in all classical treatises. 
 
 It is known that the oiclium was found in the productions of buccal 
 aphtha by Langenbec in 1839, and later studied by Berg in 1841. 
 After researches by Gruby we must cite the contributions of Robin, 1 
 who gave the parasite the name oidium albicans, by which it is now 
 generally known. Its nature, characters of vegetation, and patho- 
 logical action were definitely fixed by the researches of Grawitz, 
 Plaut, Ch. Audry, Roux and Linossier, Grasset, Charrin and Os- 
 trowsky, Tessier, and Noisette. 
 
 More recently, Dr. Vuillemin took up the question from a botanical 
 
 1 Robin. Des v£ge/taux qui croissent sur Phomme et les animaux. These de Paris, 
 1847. Histoire naturelle des veg€taux parasites, Paris, 1853. 
 
NODULAR INFECTIONS. 
 
 standpoint. 1 II was formerly believed thai the fungui of aphtha 
 was related to the yeasts and that the filamentoiM forme were of 
 but secondary importance. Vuilli min, on the contrary, thinks thai 
 Hie filaments are characteristic and must b< considered in cla 
 the parasite; then, studying the mode of reproduction, he describe* 
 clamydospores and endospores. He \&] tn i upon the presence of 
 a nucleus round both in the globules and in each filam< nt< ment. 
 
 On the ground of these importanl observations Vuillemin declares 
 the fungus of aphtha to be an ascomyces which si ion Id be d< sigi 
 as ( ndonn/ccs albicans. 
 
 The expression oidiomycosis employed by German authorities 
 and by (he author should therefore be rejected. When the ideas 
 of Vuillemin are definitely accepted I shall he glad to use the term 
 endomycosis, as Miss .Maria Daireuva 2 writing under inspiration of 
 her master, Vuillemin, thinks 1 should. In ;i very importanl work, 
 Concetti 3 classes this fungus with the group of blastomyces; accord- 
 ing to this author, it forms a transition between the latter and the 
 hyphomyces and, consequently, the term oidimn albicans should 
 be preserved. 
 
 If a patch of buccal aphtha be examined under the microsco] e 
 the fungus is found to present two different forms. At times there 
 will be seen beautiful mycelial filaments; at other times, rounded 
 or oval micro-organisms resembling yeasts. These two forms may 
 be associated or isolated. Out of thirty-one examinations made 
 by us the two forms were found together nineteen times. In twelve 
 cases there were only the yeast forms: once, pure mycelium. It is 
 possible, as is asserted b}^ Miss Daireuva. that the filamental forms 
 are never absent. The reason they are not always detected is that 
 they develop in the depth of the cream-like patch in contact with 
 or inside the mucous membrane. 
 
 The two forms above indicated are encountered in artificial 
 cultures. The oval form is mostly observed in solid media, the 
 filamentous in liquid media. These also exist in solid media, but 
 are observed then only at the beginning of development (Stocklin) 
 or in the deeper portion of the culture (Vuillemin.) 
 
 1 Vuillemin. Los characteres specifiques du champignon ilu muguet. Comptes Rendu* 
 de I'Academie des Sciences. October 24. 1S9S. 
 
 2 Maria Daireuva. Recherches sur le champignon du muguet. These de Pari.-. 18 - 
 
 3 L. Concetti. Biologie et pathologic du muguet. Archives de modecine des enfant.*. 
 August, 1900. 
 
304 INFEi 'Tl I r S DISEASES. 
 
 Characters of the Cultures. The fungus of aphtha readily 
 develops in the various nutrient media employed in bacteriology. 
 Agar-agar, gelatin, vegetables, potato, carrot, suit it well. In 
 
 liquid media the colonies soon fall to the bottom and the fluid 
 becomes clear. Trine and saliva are favorable media, while milk 
 constitutes a had one. Of all media the most favorable are carbo- 
 hydrates, especially glucose and saccharose. Whatever medium is 
 employed, the oidium gives rise to fermentation of carbohydrates, 
 resulting in the production of alcohol, aldehyde and acetic acid; 
 hence, the agreeable odor exhaled by the cultures. 
 
 The isolated fungi appear in the form of oval elements, measuring 
 from 5// to 7// in length. Proliferation occurs by lateral or termi- 
 nal budding. If a bouillon or serum culture be examined, the 
 filamentous forms are seen measuring 3// to 4// in breadth and 15/* 
 to 20// in length, which, in some instances, may exceed 400// or 
 even 500//. 
 
 It is, therefore, easy to prove the diplomorphism of oidium by 
 employing solid or fluid medium. It may be assumed that the 
 filamentous form which predominates in fluid media is due to the 
 lack of oxygen; unable to vegetate upon the surface of the fluid, 
 where no film is ever formed, the fungus falls to the bottom, and 
 then sends out prolongations toward the aerated surface. When 
 it is cultivated in a very shallow liquid medium the filaments are 
 seen to become shorter. 
 
 Other conditions also influence filamentous growth. The yeast 
 form predominates when the plant is placed under eugenesic con- 
 ditions; when the media are less favorable the filamentous forms 
 prevail. 
 
 Although the descriptions given by authors are mainly in harmony, 
 they differ in many details. These differences in opinion are, in 
 great measure, clue probably to the fact that aphtha comprises 
 several varieties. 
 
 Role of the Oidium in Human Pathology. The fungus of aphtha is 
 pathogenic for man and certain animals. In the colt, calf, sheep, 
 and hen it produces a white stomatitis which often spreads to the 
 esophagus, presenting the same characters as in man. 
 
 Oidian stomatitis, also called creamy stomatitis (stomatite 
 cremeuse), aphtha, and thrush, is commonly observed in weakened 
 or cachectic individuals, in the course of diseases which profoundly 
 debilitate the system, grave typhoid fever, urinary and tubercular 
 
NODULAR INFECTIONS. 
 
 infections, cancer, diabetes, etc. As Gubler has shown, it* develop- 
 ment is favored by the acidity of the mucous membrane. The 
 acidity is due to the excessive multiplication of microbes and to 
 fermentations which they produce in the food, particularly in milk. 
 Thus is produced a catarrhal stomatitis which weaken* there i tance. 
 The agents of aphtha being spread in the atmosphere (Lebrun, 
 Etoux, Valtat), easily develop in the altered buccal mucous mem- 
 brane. In oilier instances the parasite i transmitted directly 
 through the nursing bottle or the breast of the nurse who suckles 
 several children. Finally, it maycomefrom the milk, which is often 
 polluted with oidium lach'x, ;i plan! closely related to the aphtha 
 parasite. 
 
 It is true, however, thai aphtha does sometimes develop in healthy 
 individuals, in children by no means athrepsic, in non-cachectic 
 aged persons, and at the beginning of certain infections, notably 
 typhoid fever. It is also encountered in the mosl varied forms 
 of angina. In a total of 31 cases of diphtheritic angina thewriter 
 found it twice; of 46 cases of non-diphtheritic angina 1 showed 
 it combined with the streptococcus; of 116 cases of scarlatinal 
 angina 4 presented it. 
 
 Dr. de Stocklin's statistics show the presence of the oidium in 
 5.75 per cent, of diphtheritic cases, and 10.5 per cent, of non-diph- 
 theritic angina. 
 
 The role of the oidium albicans in these various anginas appears 
 to be of slight importance. Such is not the fact, however, when we 
 consider certain observations of oidian angina progressing as acute 
 sore throat. Teissier reported a case of this sort. 1 A woman, 
 twenty-three years of age, was abruptly seized with chills, malaise, 
 headache and fever. The following day she suffered from intense 
 dysphagia. Examination of the throat showed two small white 
 delicate membranous patches upon the palate which adhered slightly 
 to the mucous membrane. The exclusive presence of the oidium 
 albicans was observed under the microscope. In this instance 
 well as in that reported by Guimbretiere, 2 oidian mycosis started 
 and ran its course as an infection; chills, malaise, and fever were 
 the clinical features. No one would hesitate to consider these mani- 
 
 1 Teissier. Angine pseudomembraneuse produite par le champignon du rauguet. 
 Arch, de nn'-d. exp., 1S95. 
 
 -' Guimbretiere. Essai sur I'angine pseudomembraneuse due au rnuguet. These de 
 Toulouse. 1896. 
 
 20 
 
306 I. \FECTIO US DISEASES. 
 
 festations as infections, if, instead of a fungus, a bacterium was 
 detected! 
 
 I have observed a certain number of similar eases. Every year 
 a few patients 'with acute oidian angina are admitted to our wards. 
 In 1899 we had three such cases. It will suffice to mention one of 
 them, a woman, twenty-three years old, who had chills, violent 
 headache, and dysphagia, A physician called in on the following 
 day diagnosed diphtheria and advised her removal to the hospital. 
 Here we found her throat red, the tonsils greatly enlarged, and 
 white creamy patches the size of a pea occupied the soft palate, 
 right pillar, right tonsil and uvula. Our immediate diagnosis was 
 aphtha, and microscopic examination demonstrated the presence 
 of both mycelium and fungus. It required eight days' treatment 
 to bring about recovery. 
 
 The oidium ma}' be encountered in other mucous membranes 
 exposed to the air. It may invade the respiratory apparatus, 
 pharynx, esophagus, or the intestinal canal. In the stomach it may 
 penetrate into the glandular cul-de-sacs and ulcerate them. Valleix 
 and Seux noted its presence in the small intestine and cecum. It 
 has been observed in the anus, vulva and, according to Senator and 
 v. Fritsch, even in the mucous membrane of the bladder. 
 
 Whatever may be its seat, the lesion created is of a benign char- 
 acter and commonly of slight tenacity. This fungus does not 
 represent, however, a simple epiphyte. Virchow, Wagner, Parrot, 
 and Letulle have seen it penetrate quite deep into the mucous mem- 
 branes. Examining the cadavers of thirty-eight children who had 
 succumbed to aphtha, Heller found in two cases the presence of the 
 parasites in the bloodvessels; the latter were the seat of thrombosis 
 in six cases. It is, therefore, conceivable that the fungus may be 
 carried by the lymph and blood currents to the various parts of the 
 system. In fact, it has been observed in otitis media (Valentin), 
 abscess of the gums (H. Grasset), submaxillary abscess (Charrin), 
 and suppurating parotiditis (Guido). At the necropsy of a man 
 who died with right hemiplegia, Zenker 1 found the left cerebral 
 hemisphere full of small, round, granular abscesses, containing the 
 parasite. The starting-point was attributed to the thick membranes 
 of aphtha occupying the throat. This is the first observation of the 
 kind. 
 
 1 Zenker. Soor in Gehirnabscessen. Berichte der Gesellschaft f. Natur unci Heil- 
 kur.de, 1861. 
 
NODULAR INFECTIONS. 307 
 
 In a child who died from 9 buccal aphtha twelve days after birth 
 Ribbert 1 round both cerebral hemi phere tudded with miliary 
 abscesses, containing oidian filaments. G. Guidi 2 has likewise found 
 the oidium in the pus of cerebral abscesses in a girl three years old. 
 Finally, Dr. Monier 8 published the observation of a cerebral oidian 
 abscess expressing itself, during life, by hemiplegia with Jacksonian 
 epilepsy. 
 
 Thf respiratory apparatus may also be invaded in certain cs 
 
 The oidium lias been found in the pneumonic torn- in :i four-yar-old 
 
 child, in the lung of a little girl suffering from fetid bronchitis, and 
 in a pulmonary lesion simulating a hydatid cysl of the liver. Guidi 
 
 observed the parasite in a pulmonary absceS£ occurring in a child 
 three months old, which perforated a pulmonary artery, and thus 
 caused sudden death by hemorrhage. 
 
 In some instances the nature of the disease has been recognized 
 during life. In an observation of Preyhan, the patient 4 suffered 
 from pulmonary disease, with hemorrhagic pleurisy; her expectora- 
 tion was sanguinolent and exhaled the odor of fresh yeast, and 
 contained clots formed of the fungi of aphtha. 
 
 Oidian lesions have been observed in the various segments of the 
 digestive tract, notably in the stomach and intestine. In an observa- 
 tion of Schmorl 5 the parasite invaded the kidneys and there pro- 
 duced miliary abscesses occupying the surface of the organs. 
 
 These observations are very interesting, since they demonstrate 
 that oidiomycosis such as is experimentally produced in animals 
 is a possible event in human pathology, and probably of more 
 frequent occurrence than the cases reported seem to indicate. 
 
 Experimental Oidian Mycoses. Klemperer 6 is to be credited 
 with having demonstrated that intravenous injection of a culture 
 of the oidium albicans induces a fatal disease, characterized by 
 numerous granulations in the kidneys. 
 
 1 Ribbert. Weitere Untersuchungen liber das Sehiksal pathogener Pilze ini organis- 
 mus. Deutsche med. Wochenschrift, 1SS5. 
 
 2 Guidi. Ueber Soor, seine Mykologie und Metastasenbildung. Wiener med. Blatt., 
 1S95. 
 
 3 Monier. Considerations sur les mycoses ceri'brales et plus particulierement sur la 
 generalisation dumuguet. Gaz. mod. de Nantes, 1S97. Pineau. Le muguet infectieux. 
 These de Paris, 1S97. 
 
 4 Preyhan. Pneumonomycosis. Berliner klin. Wochenschrift. 1891. 
 
 5 Schmorl. Ein fall von Soormetastase in der Xiere. Centralblatt f. Bakteriologie, 
 1891, Bd. ix. 
 
 6 Klemperer. Ueber die Xatur des Soorpilzes. Ccntralb. f. klin. Medicin. l^ v ". 
 
308 IXFECTIO US DISEASES. 
 
 Experiments of Roux and Linossier showed the possibility of 
 nervous symptoms in the inoculated animals. My own researches 
 confirm the descriptions of these authors and demonstrate the 
 frequency and variability of the nervous phenomena. 
 
 The more numerous experiments of Grasset 1 added some new 
 facts. These investigations show that intravenous injection pro- 
 duces foci not only in the kidneys, but at times also in the peri- 
 toneum, liver, intestine, heart, and spleen. The suprarenal capsules 
 are the seat of lesions appreciable only under the microscope. 
 
 The first researches which I published on this subject 2 com- 
 pleted our knowledge of the localizations of the oiclium, the 
 histological characters of the lesions, exaltation of virulence, and 
 particularly the modifications presented by the serum of vaccinated 
 animals. 
 
 After inoculation the animals remain healthy for a day of two; 
 then they begin to emaciate. Death may occur suddenly. It is 
 often preceded by paralytic manifestations which, with certain 
 cultures, are seldom wanting. The morbid phenomena grow worse, 
 and the animal succumbs in a state of general exhaustion after 
 suffering, in some cases, from convulsions. The necropsy reveals 
 granulations disseminated in various parts of the organism. 
 
 Histological Study of the Oidian Tubercle. The histological ex- 
 amination must be directed to the kidneys invaded with nodules. 3 
 In preparations stained with alum-carmine, and picrocarmine, the 
 granulations appear, under slight magnification, in the form of 
 small masses, which are distinguished from the surrounding tissue 
 by then red color; their limits are not absolutely clear and sharp. 
 Rows of cells extend from the granulations and form prolongations 
 which enter the tubules of the kidney. When more highly magnified 
 the nodules are seen to be composed of collections of embryonal 
 cells, the yellowish portions corresponding to degenerated elements 
 fused into a homogeneous mass (Fig. 10). 
 
 Vaccination Against the Oidium. Noisette has shown that the 
 fungi of aphtha degenerate when cultivated in the serum of animals 
 previously infected with the mycotic fungus, and a short time after- 
 
 1 Grasset. Etude d'un champignon pyogene parasite de l'homme. Arch, de med. 
 exp., Sept., 1893. Etude sur le muguet. These de Paris, 1894. 
 
 2 Roger. Modifications du serum chez les animaux vaccines contre l'oidium albicans. 
 Soc. de biologie, July 4, 1896. 
 
 3 Roger and Josue. Des alterations du rein dans l'oi'diom3 r cose experimehtale. 
 Societe anatomique, January 2, 1897. 
 
NODULAR INFECTIONS. 
 
 309 
 
 ward they cease to multiply. This reaction was taken advantage 
 of by the author in differentiating the diverse varieties of oidium 
 separated by him. 
 
 I'm;. 10. 
 
 The upper figure represents a normal kidney : the middle one a highly hypertrophied 
 kidney whose surface is covered with oidium granulations; the lower figure represents 
 a transverse section of the diseased kidney (natural size). 
 
 The serum of vaccinated animals acts more energetically upon 
 the plant than that of infected ones. In fact. I have learned that 
 
310 INFECTIOUS DISEASES. 
 
 it is possible to confer quite a remarkable degree of immunity upon 
 the rabbit. To succeed in this experiment it is necessary to begin 
 with a weak culture, of which a very small dose is injected into the 
 veins. Tin" doses must be slowly and progressively increased until 
 the animal is able to endure twice or even three times the fatal 
 amount. 
 
 The Agglutinating Power of the Serum. Having succeeded in 
 conferring a notable degree of immunity upon the animals, the 
 writer was naturally led to investigate whether the serum of the 
 animals thus treated manifested modifications similar to those 
 observed in animals which had received various bacteria. First 
 studying the serum of animals submitted to subcutaneous and 
 intraperitoneal inoculations, he noticed that aphtha develops in 
 this medium as well as in the normal serum. This result need not 
 be wondered at, since, under these conditions, there has been no 
 increase in resistance. If, however, the serum of rabbits vaccinated 
 by intravenous inoculations be studied, other results are obtained. 
 
 Let us take a culture grown in normal serum and inoculate a 
 trace of it into tw r o tubes, one containing normal serum, the other 
 serum of the vaccinated animal. At the end of twenty-four hours 
 development is very luxuriant in the normal serum. In the other 
 serum a few flocculi occupying the bottom of the tube may at times 
 be seen ; at other times no development is apparent, the fluid remains 
 perfectly clear. At the bottom of the tube, however, there is found 
 an accumulation of small granules which manifest a strong tendency 
 to agglutinate so as to sometimes form a single mass. When the 
 fluid is shaken the granules are dispersed, but are not numerous; 
 the culture is a poor one. Increased development is observed on 
 the following days, but the culture remains long or always inferior 
 to that of the control. 
 
 The vegetating power of the oidium becomes so weakened in the 
 serum of the vaccinated animal that if, at the end of four or five 
 days, another tube containing the same kind of serum be inoculated 
 with this culture, the fluid remains sterile. 
 
 A microscopic examination will suffice to show why the cultures 
 present such different aspects. 
 
 At the end of twenty-four hours the normal serum contains 
 (Fig. 11) filaments associated with yeast forms; the latter, at times 
 provided with a terminal or lateral bud, are formed of a mass of 
 protoplasm deeply stained with methylene blue and limited by 
 
NODULAR INFECTIONS. 
 
 31 1 
 
 :i very thin and colorless cuticle. These fungi are free, olil 
 or united into groups of twos and three . Even when thus adher- 
 ing it is readily seen thai each of them hac ite proper individuality; 
 their cuticles are clearly distinct; there i- only juxtaposition, bul 
 no fusion with neighboring elements. 
 
 The filamentous forms differ from the preceding by the more 
 pronounced development of their cuticles, the small amounl of their 
 
 i ; ii, ii 
 
 Appearance of a culture of oidium albicans in a normal serum. Beautiful fila- 
 ments are seen alongside of .yeast forms, at times provided with a terminal or lateral 
 bud. The non-homogeneous protoplasm presents dark and light parts; it is limited 
 bv a thin and colorless cuticle. 
 
 protoplasm, and weaker affinity for the aniline dyes. The filaments 
 are undivided, ramified, or provided with lateral buds having the 
 form of yeasts. 
 
 When the culture developed in the serum of the vaccinated animal 
 is examined the appearances are found to be quite different. 
 
 Let us first consider a solitary fungus : The protoplasm is colored 
 as in the normal state; it has the same appearance and dimensions. 
 
312 
 
 IXFECTIO US DISEASES. 
 
 It is surrounded by a colorless, hyaline, at times a slightly striated 
 mass, with sinuous, illy-defined borders, the length of which is five 
 or six times that of the normal cuticle. The elements are seldom 
 isolated: they form couplets, groups of three, and often groups of 
 voluminous sizes, made up of from ten to thirty elements. It is 
 easy to demonstrate that the condition here is not one of simple 
 juxtaposition, but one of fusion of the cuticles and formation of a 
 true zooglea. The filaments are here and there intimately united 
 to the fungi, which are either solitary or agglutinated. In other 
 
 Fig. 12. 
 
 Appearance of a culture of oidrum albicans in the serum of the vaccinated animal. 
 The elements are united in voluminous agglomerations and surrounded by a colorless 
 hyaline mass. The filaments are likewise composed of a protoplasmic mass surrounded 
 bv a very thick cuticle. 
 
 instances one extremity of a filament is lost in the midst of a collec- 
 tion of fungi to which it seems to have fused. 
 
 Conclusions Concerning the Nature of Oidiomycosis. Oidio- 
 mycosis does not differ from bacterial infections any more than the 
 latter do from each other. In fact, it is evidently possible to express 
 in one general formula the mode of action of the various bacteria. 
 When, however, we come to considerations of general pathology, 
 we reach conclusions which, in the majority of instances, are appli- 
 cable only to certain groups of microbes, but not to all. Oidiomycosis 
 is, therefore, not to be compared to a schematic bacterial infection; 
 
NODULAR INFECTIONS. 313 
 
 the question is whether ii resembles some well-determined infec 
 disease. By reason of the lesions ii produces in animals, the oidium 
 closely resembles the pyogenic microbes, notably the 3taphylococ 
 Indeed, in both cases subcutaneou inoculation La followed by the 
 formation of an abscess. When injected into the vein- the staphy- 
 lococcus, like the fungus of aphtha, gives rise to miliary ab <■• 
 The analogy is continued even in the localization, since the staphylo- 
 coccic abscesses are often confined to the kidneys; occasionally the 
 cocci invade other organs, notably the myocardium, liver, lungs, 
 and brain. The oidium is equally capable of affecting the same 
 organs in the same manner. 
 
 Moreover, vaccination againsl oidiomycosis is as practicabli 
 in bacterial infections. We have further 3een that, in the -'rum 
 of animals vaccinated against oidiomycosis, modifications similar 
 to those observed in animals vaccinated againsl bacteria are pro- 
 duced. In both cases the serum becomes bactericidal; ii inhibits 
 and weakens the development of the pathogenic agent. 
 
 The idea of infection is not established on etiological or patho- 
 genical bases, but on clinical data, to wit, on the reactionary modes 
 of the affected system. The facts above stated demonstrate thai 
 the organism acts toward the oidium as it does toward bacteria. 
 Oidiomycosis, then, is rightly classed with infectious diseas 3. 
 
 Pathogenic Role of Yeasts. 
 
 The study of oidium is rendered particularly interesting by the 
 fact that this plant represents the best known member of an im- 
 portant group of pathogenic agents. In reality, a great number 
 of yeasts give rise to similar lesions. Thus. Miss L. Rabinowitsch 1 
 out of fifty species of yeasts taken in Koch's laboratory found 
 seven pathogenic ones. Noisette, employing a certain yeast that 
 is currently on the market, showed that its inoculation produced a 
 mycosis similar to that caused by the oidium albicans. San Felice 2 
 found in the juice of fermented fruits a pathogenic yeast, the sac- 
 charomyccs neo for mans . 
 
 We may also cite the saccharomyccs lithogens of San Felice, the 
 <S. niger of Maffucci and Sirleo, the S. sepdcus of Gaetano, etc. 
 
 1 Lydia Rabinowitsch. Untersuchungen uber pathogen Hefearten. Zeitschrift f. 
 Hygiene, 1S95, Bd. xxi. 
 
 ' : San Felice. Ueber eine fur Thiere pathogene Spros>pilzart. Oentralblatt f. Bak- 
 teriologie. 1893. Bd. xvii. 
 
314 TNFEi ■ TIO I 'S DISEASES. 
 
 Bere, ;lu'ii. are widely distributed plants, some of them daily em- 
 ployed in the industries, which are capable of engendering diseases. 
 
 It may be objected that these are merely experimental results, 
 and thai, in order to produce them, such procedures have been 
 resorted to a- are never realized in the natural course of events. It 
 is well to know, however, that yeasts are frequently found in the 
 organism. Their presence has been noted in cutaneous ulcers 
 I Babes), in suppurated dental pulps (Miller), in uterine and vaginal 
 discharges (Colpe), in hypertrophied tonsils (de Simoni), in the brains 
 of hydrophobic men and animals (Memmo), and cultures of these 
 parasites have at times produced fatal disturbances in animals. 
 
 Recent contributions tend notably to increase the role of yeasts 
 in pathogenesis. An interesting observation of chronic pyemia was 
 reported by Busse. 1 The symptoms were due to a saccharomyces 
 the cultures of which induced in animals disturbances similar to 
 those observed in man. There appeared also a series of contributions 
 demonstrating that in man, as well as in certain animals, blasto- 
 mycetes are frequently encountered in various neoplasms (San Felice, 
 Roncali, Corselli e Prisco, Ajevoli, Secchi, Wlaeff, etc.). It will 
 suffice to mention one among the numerous observations, that of 
 Curtis. 2 It was a case of a myxosarcoma of the thigh, comprising 
 yeast in a state of purity which was successfully inoculated into 
 the connective tissue of a rabbit. This does not mean that yeasts 
 represent the exclusive agents of tumors, but they really seem to 
 give rise to some of them. This is sufficient inducement to draw 
 more attention to their study. 
 
 We are thus in the presence of a new chapter, in its formative 
 stage, in the history of infectious diseases. Blastomycetes claim a 
 place alongside bacteria and streptothrix. Oidiomycosis may now 
 be considered as the type of mycotic infections. 
 
 Actinomycosis. 
 
 Biological Characters of Actinomyces. Actinomycosis is a disease 
 due to the presence of a special plant belonging to the class of strepto- 
 thrix or oospora, and occurring in the form of radiate collections 
 visible to the naked eye. They are small, yellow, opaque grains of 
 
 1 Busse. Ueber parasitare Zelleinschlusse und ihre Ztichtung. Centralb. f. Bakte- 
 riologie, 1895, Bd. xvi. Ueber saccharomyces hominis. Virchow's Archiv, 1895, Bd. cxl. 
 
 2 Curtis. Contribution a 1 'etude de la saccharomycose humaine. Annales de l'Institut 
 Pasteur, 1896. 
 
nodu LA B INFECTIONS. 
 
 316 
 
 variable size. Commonly of ;i golden yellow color, when young 
 I, hey are whitish and translucent; in other instance their color i- 
 dark green or sepia. 
 
 The grain may easily be crushed. It is formed of small balls 
 measuring from 0.3/* to 0.5/* in breadth and 0.18ft to 0.35/i in 
 length, and when slightly magnified it appears in mulberry form. 
 
 Each granulation is composed of a central ma I ig. L3j, whence 
 numerous prolongations radiate, mosl of which end ina club-shaped 
 enlargement. These enlargements were once considered to be 
 bearing organs, bul they simply represent mycelial involution swell- 
 ings. Their weak vitality explains their frequenl infiltration with 
 calcareous salts. 
 
 Fir;. 13. 
 
 Granulation of actinomycosis. X 600. 
 
 The actinomyces resist the action of acids, alkali, chloroform, ami 
 ether; hot alkalies render them pale and disfigure them : water, even 
 salt water, swells and deforms them. 
 
 Cultivation of Actinomyces. Actinomyces has quite often been 
 successfully cultivated in the artificial nutrient media employed in 
 bacteriology. Solidified serum was employed by Irsael. 1 Small 
 nodules composed of grains similar to those observed in the actino- 
 mycotic lesions of man and animals made their appearance in the 
 medium on the fourth day. Development is very active on glycerin- 
 
 1 Israel. Ueber die Cultivirbarkeit d. Actinomyces. Virchcw's Arch.. 1SS4. Bd. xcv. 
 
3 1 6 INFECTIO US DISEA SES. 
 
 ated agar-agar; according to Kischensky, 1 colonics containing rods 
 similar to tubercle bacillus appear as early as the second day; then 
 there appears a1 each extremity a swelling which stains intensely. 
 Toward the sixth or seventh day the rods become elongated into 
 filaments which, after two or three weeks, bear at their extremities 
 involutive forms which can no longer be stained. 
 
 Actinomyces may also be cultivated in liquid media, such as 
 serum, milk, and bouillon. Cultures succeed also upon potatoes and 
 in eggs. 
 
 The spores never occur in living organisms. They are encoun- 
 tered only in artificial cultures, to which they impart a notable 
 resisting power. 
 
 Fig. 14. 
 
 Culture of actinomyces in bouillon, seven months old, after twenty-four hours' incu- 
 bation. Numerous filaments with club-shaped extremities (to), hyaline bulbs (g), 
 representing clubs in process of degeneration, and a few spore-bearing filaments 
 (s). (Berard and Nicolas.) 
 
 Actinomyces has been variously designated and classed by different 
 authorities. The point conclusively established is that it is not a 
 bacterium, but a fungus, to be placed permanently beside the 
 streptothrix. 
 
 Inoculation of Actinomyces. Johne was the first successfully to 
 inoculate actinontyces, by operating upon a heifer and two calves. 
 It has since been possible to produce the disease in the rabbit and 
 guinea-pig, but not invariably. The best results are obtained by 
 
 1 Kischensky. Ueber Actinomj-cesreinculturon. Arch. f. exp. Path, und Pharmakol, 
 18S9. 
 
NODULAR INFECTIONS. .",17 
 
 the employment of anaerobic culturei or tho e made in i ■ ■ Lieb- 
 man 1 thinks the failures are due to the supposed facl that, unlike 
 the great majority of virulenl agenl . actinomyces is attenuated in 
 passing through the bodies of man and animal ; al the same time 
 its vegetability diminishes in notable proportions. If would be 
 possible for the parasite to recover its powers of vegetation and 
 virulence by cultivation in a plant. Various experimenters, how- 
 ever, unsuccessfully repeated the experiments of Liebman. 
 
 Etiology. While very frequenl among certain animals, especially 
 the l)ovida v , actinomycosis is qoI rare in man. In Bergmann's 
 clinics in Berlin L20 cases were collected in six years. Num< 
 observations have been reported in France, Switzerland, Bolland, 
 and England. In America the firsl case was observed in L888 by 
 Bulhoes and Magalhaes. Since that time a greal oumber of - 
 have been observed in the New World; actinomycosis seems to 
 be of frequent occurrence there, and renders suspicious the meal 
 imported to Europe. 
 
 Actinomycosis may be observed in horses, sheep, and hogs, the 
 infection originating from plants upon which these animals are fed. 
 Men are also often affected in the same manner, in handling plants 
 or accidentally swallowing ears of barley, and in many other ways 
 which often remain unrecognized. Alongside the cereals we musl 
 place the young shoots of thorny shrubs and the bark of v 
 altered by moisture and mouldiness. 
 
 It is well to mention that the parasite has been found in milk 
 (Bollinger) and eggs (Artant), hence the possibility of contamination 
 by food. 
 
 Evolution of Actinomycosis. The anatomical and clinical evo- 
 lution of actinomycosis is different in man and in animals. In 
 man suppurating foci are encountered: in animals hard tumors, 
 resembling sarcoma. It was once believed that these differences 
 depended upon differences in the parasites. The study of etiology, 
 however, and especially the experiments of Irsael. Bostroem, and 
 Rotter, who transmitted the disease from man to animals, demon- 
 strated the unity of the infection. The peculiar characters of the 
 malady in man are due to the fact that the parasite is associated 
 with common pyogenic microbes which add their action to tl.; 
 the actinomyces. In certain observations in which actinomyces 
 
 1 Liebman. L'actmomice dell' nomo. Archiv per le sc. med., 1890. 
 
: 1 1 8 IXFECTIO US DISEA SES. 
 
 was found to be alone the disease manifested an evolution similar 
 
 to that observed in animals — i. e., a solid tumor constituted the 
 lesion. Suppuration is not produced in animals, because they are 
 less sensitive to the action o( pyogenic agents. 
 
 Therefore, in order to form an idea of the lesions created by the 
 parasite when acting alone, actinomycosis should be studied in 
 animals. In the bovidse the disease is characterized by a volum- 
 inous tumor, generally located in the lower jaw and invading the 
 adjacent muscles. In other instances it begins in the periosteum; 
 the bone becomes excavated and filled with morbid matters. The 
 teeth are loosened, and mastication is impossible. If the tongue 
 is invaded, this organ becomes hard (holzzunge (woody-tongue) of 
 German authors) and the animal can no longer use it. The pharynx, 
 respiratory passages, and spine may also be involved. 
 
 The disease is seldom generalized, since the animals are killed 
 too soon. Nevertheless, a few cases exist in which the evolution 
 was altogether similar to that of acute miliary tuberculosis. Such 
 for instance, is the very interesting observation made by Pflug upon 
 a cow. 
 
 Pathogenic Streptothrix. There exist certain parasites akin to, 
 but not identical with, actinomyces, which are also able to produce 
 lesions. 
 
 Aside from streptothrix farcinosa, which is not pathogenic for man, 
 we may mention four varieties of streptothrix encountered in the 
 human species: the S. Fozrsteri, the S. asteroides (Eppinger), the 
 S. of madura foot, and the S. of Poncet and Dor. 
 
 Madura foot or mycetom is an affection particularly frequent in 
 India, but observed also in America and Algeria. Its invasion is 
 characterized by a painless and diffuse swelling of the integuments 
 of the foot; then appear little tumors which are at first hard, but 
 subsequently soften, break down, and give rise to a sanious pus 
 containing grayish, yellowish, or black granules. The lesion always 
 remains local; there is no propagation by contiguity or by embolism. 
 The affection almost invariably terminates in death. 
 
 This parasite is easily cultivated in vegetable infusions and upon 
 potatoes, to which it often imparts a fine red color. 
 
 Pseudoactinomycosis of Poncet and Dor is expressed by lesions 
 analogous to those of true actinomycosis, 1 but the yellow grains, 
 
 1 Dor. Une nouvelle mycose &graines jaunes. Gazette hebdomadaire, 1896. Poncet. 
 De l'actinomycose et des mycoses cervico-faciales. As*, francaise de chirurgie, 1S9G. 
 
NODULAR INFECTIONS. 319 
 
 which are less numerous, are much larger and more ea ib cm hed. 
 There are already thirteen observation of this myco i reported, 
 which seems not to he of very rare occurrence. 
 
 Mycoses in Man. Besides the streptothrix there are plant* capable 
 of producing lesions more or less similar to those of actinomy© 
 The aspergillus and mucors may especially be mentioned. 
 
 Paltauf observed a pharyngolaryngeal phlegmon with intestinal 
 ulcerations and pneumonia; in all the foci was found a mucedina 
 similar to the mucor corymbifer of Lichtheim. 
 
 A woman expectorated fragments of pulmonary tissue containing 
 masses of aspergillus (Rother). In the case of a young man who 
 was suffering from aspergillian mycosis of the trachea, inhalations 
 of iodine vapor sufficed to cure the affection. Wheaton and Etc - 
 published similar observations. 
 
 If, in addition to these clinical facts, we bear in mind the experi- 
 mental results demonstrating thai various forms of mucor or of 
 aspergillus may be pathogenic, we are led to the assumption that 
 a good many infections must be dependent upon more highly organ- 
 ized parasites. At the present day we are not thoroughly acquainted 
 with any except actinomycosis, which may, therefore, be regarded 
 as the type of a whole group. 
 
 Tumors and Infections. 
 
 We do not intend to take up the complex and as yet obscure 
 history of tumors. Although convinced of their parasitic origin, 
 we must frankly acknowledge there are no irrefutable facts to 
 support this opinion. One may take analogies as a basis. It must 
 be recognized, however, that most of the observations upon tumors 
 of parasitic origin thus far reported concern sarcomatous production.-. 
 Sarcoma simulates tuberculosis in the dog, actinomycosis in bovidae, 
 and botryomycosis in the horse. On the other hand, it is un- 
 doubtedly true that sarcomata strikingly resemble inflammatory 
 lesions; there is structural analogy, at times identity. The oppo- 
 nents of the parasitic theory would readily yield this group of 
 tumors, but emphatically reject the infectious nature of epithelioma. 
 
 There is no doubt that the time is fast approaching when tumors 
 will be differently classified. Lesions of tuberculosis, of glanders, 
 and of syphilis which twenty years ago were still described among 
 the neoplasms by eminent histologists (Yirchow. among others) 
 
321 ' INFECTIOUS DISEASES. 
 
 have already been se1 aside. The same is true with actinomycotic 
 
 tumors. Employing the term tumor in its traditional sense, it may 
 be said that there arc parasitic tumors. On the other hand, the 
 relations uniting chronic inflammations with adenomata, and these 
 with epitheliomata, seem to prove that reactions caused by the 
 commonest infectious agents may evolve toward the formation of 
 neoplasms. Mechanical irritations of tissues act in the same manner. 
 Traumatism, contusion, and, above all, repeated friction and irri- 
 tation, may lie followed by the development of tumors. The similar 
 role of chemical irritation is illustrated by the development of 
 pulmonary sarcoma in men employed in arsenical cobalt factories 
 (Hoerting and Hesse). Finally, larger parasites are also capable 
 of giving rise to tumors. Albarran and Bernard had the opportunity 
 to study a vesical tumor presenting the appearance of epithelioma, 
 which appearance was due, in reality, to the ova of bilharzia hema- 
 tobia present. With Cadiot and Gilbert 1 the writer observed, in 
 an old dog, tumors of the vulva which had deformed the vagina 
 and perforated the wall at several points. Microscopic examination 
 showed that these productions were formed of round cells, in the 
 midst of which acarina were seen. 
 
 Experimental Tumors of the Thyroid Gland. The most ordinary 
 inflammations may likewise give rise to neoplastic masses in animals. 
 In this connection we have reported the results of an experiment 
 made in conjunction with Dr. Gamier. 2 
 
 On May 9, 1898, we injected five drops of a diluted culture of the 
 staphylococcus aureus into the carotid artery of a rabbit so as to 
 reach the thyroid vessels. Five days later we injected the same 
 amount of the same culture into the other carotid. This rabbit 
 survived three months, until August 11th. It bore on the right 
 side of the neck an irregular but clearly encapsulated tumor as 
 large as a walnut. This hard tumor had the appearance of a sarcoma 
 and contained in its interior softer caseous masses. It represented 
 the right lobe of the thyroid gland extremely developed. The left 
 lobe had preserved its normal form and connections, but looked 
 enlarged. 
 
 In microscopic sections of the tumor the thyroideal tissue was 
 
 1 Cadiot, Gilbert, and Roger. Les tumeurs malignes chez les animaux. La presse 
 mSdicale, Jul}- 14, 1894. 
 
 2 Roger and Garnier. Recherches exp^rimentales sur les infections thyro'idiennes. 
 La presse medicale, August 9, 1900. 
 
NODULAR INFECTIONS. 321 
 
 completely unrecognizable; nowhere was there any trace of lobule, 
 vesicle, or colloid substance. This tissue was made up of collections 
 of epithelial cells withoul any orderly arrangement, between which 
 a few connective tissue bands were visible. The epithelial cells 
 appeared to be profoundly modified; the nuclei were very large, 
 vesicular, irregular, and faintly tinged by the ordinary dyes. Large 
 numbers of leucocytes infiltrated the entire tumor; they were often 
 disseminated between the cells; elsewhere they were united in the 
 shape of little islands; their nuclei were small, deeply colored, and 
 contrasted markedly with the lighl nuclei of the epithelial cells. 
 
 The left lobe presented the same structural alteration, bul had 
 not undergone Hie enormous hypertrophy noted in the righl one. 
 
 It was quite difficult to assign a place in nosology to this morbid 
 production. In reality we were in the presence of a genuine 
 neoplasm, and the groat development of the tumor could not be 
 attributed solely to the infiltration by leucocytes. In order to 
 produce this enormous mass the epithelial tissue had abundantly 
 proliferated. It appears, therefore, that the cells had responded 
 to the morbid excitement by increased activity, resulting in con- 
 siderable multiplication of the epithelial elements and hypergonosis 
 of tissue. Later, all these newly-formed cells degenerated, necrotic 
 foci appeared here and there, and leucocytes wandered in. This, then, 
 was a case of true inflammatory neoplasm in process of degeneration. 
 
 Attempts to Inoculate Cancer. If tumors could be successfully 
 inoculated, this would be a powerful argument in support of the 
 parasitic theory. The facts thus far reported are far from demon- 
 strative. Although it seems to be proved that cancer is inoculable 
 from one part to another part of the organism affected. it> trans- 
 mission from a diseased to a healthy individual is doubtful, in spite 
 of a few observations of cancer of the penis in men who had had 
 sexual intercourse with women suffering from uterine cancer. Ex- 
 perimental pathology furnishes no better results ; thus far no experi- 
 menter has succeeded in transmitting human cancer to animals, nor 
 from animal to animal of similar species. The only positive facts, 
 those of Hanan and of Moreau, concerned rats and mice. According 
 to Menetrier's remark, inoculation is not successful except when 
 practised upon animals of the same family in which cancer has 
 already made its first appearance, and from that moment on it 
 affects several individuals. This is practically equal to the grafting 
 of the disease into the individual itself. 
 
 21 
 
322 / SFECTIO US DISEASES. 
 
 Our own attempts, repeated a great number of times, gave no 
 results. We inoculated the cancer of man into dogs, rabbits, and 
 rats, and the cancer of dog into dogs and rabbits. The inoculations 
 w< re made beneath the skin, into the peritoneum, and peripheral 
 
 veins: lastly, in view of the frequency of secondary cancer in the 
 liver, we made inoculations through the portal vein. We constantly 
 failed. We failed even when we endeavored to inoculate into can- 
 cerous dogs fragments of their own tumors. In two cases we believed 
 we obtained positive results. In one of them, however, the tumor 
 found in the spleen of an inoculated dog did not present the same 
 histological characters as the mammary neoplasm which had served 
 for the experiment. In the other instance, the lesions presented the 
 macroscopic characters of cancer, but were in reality dependent upon 
 tuberculosis. 
 
 These two observations compel us to regard as doubtful the old 
 observations and all those in which no careful study of the histological 
 and bacteriological characters of the lesions were made. 
 
 Negative results, however, do not warrant denial of the parasitic 
 nature of tumors. They only suggest modification of experimental 
 methods, since they demonstrate that the problem will not be solved 
 by merely multiplying inoculations according to usual procedures. 
 
m 
 
 (II A PTEB X I. 
 CELLULAR DEGENERATIONS. 
 
 le of Toxins in Hi" Development of Cellular Degenerations. Study of tli<- Different 
 Varieties of Degenerations. Cloudy Swelling. Qranulo-albuminoui Degenera- 
 tion, Granulo-fatty Degeneration. Fattj Degeneration. Amyloid Degeneration. 
 Pigmentary Degeneration. 
 
 The description which has been given <>!' inflammatory phenomena 
 has shown what arc the reactions excited a1 the point attacked by 
 infectious agents. The purpose of these reactions is to circumscribe 
 the lesion and to oppose (he diffusion of microbes and toxins. Unfor- 
 tunately, the barrier is too often inadequate: the microbes and espe- 
 cially the toxins succeed in impregnating the organism and produce 
 various general manifestations. 
 
 A local lesion, even when circumscribed, permits the diffusion of 
 substances which impregnate the surrounding tissues. In absct 
 the liver, for instance, if the local lesion is intense and of long stand- 
 ing, secondary alterations occur in the hepatic cells; in some cases the 
 cells in immediate contact with the focus are affected; in other 
 instances the whole gland suffers. These secondary changes, how- 
 ever, differ from the lesions produced at the primary focus. The 
 changes observed are not inflammatory alterations, but degenera- 
 tions. 
 
 Although cellular degenerations often predominate in the part 
 primarily attacked, the process may in some cases gradually involve 
 other tissues or organs. A suppuration localized in a bone or joint 
 may thus be complicated with fatty or amyloid degeneration of the 
 principal viscera. An important role was once attributed to hyper- 
 thermia, insufficient supply of oxygen, respiratory and digestive 
 disorders in the genesis of steatosis. It is at present known that 
 these pathogenic factors are of little importance: the true cause of 
 the morbid events is found in the diffusion of toxins. 
 
 The first stage of cellular degeneration consists in cloudy swelling. 
 The cells are swollen and filled with an albuminous or serous fluid 
 holding small granules in suspension. The latter present two stages : 
 at first, there is granulo-albuminous degeneration ; later, granulo- 
 
324 l -V/ 'IX ' TIO US DISEASES. 
 
 fatty degeneration. In the former case acetic acid swells the gran- 
 ules and then dissolves them; in the latter instance the granules are 
 colored dark by osmic acid. This morbid state is observed in a great 
 number of inflammations; it affects the protoplasm and may involve 
 the nucleus and nucleolus of the cells. 
 
 At a more advanced stage we find fatty degeneration, properly 
 so called, or steatosis. This process, which plays a notable role in 
 pathology, must not be confounded with fatty infiltration, which is 
 observed, for instance, in obesity. In the case of fatty infiltration 
 there is simple deposition of fat in the interior of the cell ; the proto- 
 plasm may be pushed aside, but its activity is not appreciably dis- 
 turbed. On the other hand, in the case of steatosis or fatty degen- 
 eration the protoplasm itself is transformed into fat. Under the 
 influence of nutritional disturbances the proteid substance suffers a 
 peculiar metamorphosis; hence the physiological function of the 
 element is profoundly affected or even completely lost. 
 
 Mucoid or colloid degeneration is observed in the epithelial cells. 
 It is characterized by the deposition of mucinoid substance in the 
 interior of the protoplasm. This may be compared to vacuolar 
 degeneration in which vacuoles appear to be present in the cell. 
 This phenomenon is in reality due to the presence of small cysts 
 filled with an albuminoid substance. In colloid degeneration the 
 material elaborated in the diseased cells may be expelled. If it enters 
 an excretory duct it will be eliminated from the system. Such, for 
 example, is what occurs in the kidney; the colloid masses exuded 
 from the cells unite, coalesce, and form cylinders which are detected 
 in the urine by microscopic examination. When the substance is 
 retained at the point of elaboration it gives rise to the development 
 of more or less voluminous cysts. Thus are explained the cystic 
 degenerations of the kidney and liver, the formation of colloid cysts 
 in the thyroid gland, etc. As the same process, however, may like- 
 wise affect pathological cells, cysts may be produced in ttimors. The 
 ovarian cyst, for instance, is looked upon as an epithelioma charac- 
 terized by colloid degeneration. 
 
 Another important variety of degeneration is represented by hya- 
 line degeneration. It is essentially characterized by the production 
 of refractive, homogeneous masses. It is frequently encountered in 
 cases of nephritis, in inflammation of the ovary, and in tuberculosis ; 
 it is not rare in the small aneurisms found in the walls of tubercular 
 cavities. 
 
CELLULAR DEQENERA TI0N8. 326 
 
 Parallel with hyaline degeneration may be placed transparent 
 degeneration, observed by Hanoi and Gilbert in the liven of pel 
 dead of cholera. The protoplasm of the hepatic cells become com- 
 pletely transparent, Lhe nucleus alone persi ting. 
 
 Lastly, Zenker's waxy degeneration is generally considered to 1^; 
 the same as hyaline degeneration. K is an alteration attacking the 
 striated muscles. If was firsl encountered in typhoid fever, and 
 subsequently observed in a greal number of infections. [1 ma] 
 be experimentally produced by tetanization of the muscles. It is 
 essentially characterized by swelling, hyaline metamorphosis, and 
 fragmentation of the muscular I issue 
 
 There is no accurate knowledge concerning the nature of hyaline 
 degeneration. It lias been noticed that the substance infiltrating 
 the cells resists reagents. This fact is one of the n hy if 
 
 is compared to another variety of degeneration, viz., amyloid degen- 
 eration. 
 
 Hyaline degeneration must not be confounded with glassy degen- 
 eration. The latter is essentially characterized by a transformation 
 of the cell, all parts of which lose their histochemical properties. 
 The protoplasm, nucleus, and nucleolus are no longer differentiated. 
 It would seem, therefore, that this process should be identified with 
 fibroid degeneration or coagulation necrosis. This is a process sim- 
 ilar to the one presiding over the coagulation of organic substances 
 containing fibrin. 
 
 It is often stated that glassy degeneration is the first stage of 
 caseous degeneration. In fact, it seems certain that the cells are 
 attacked by coagulation necrosis before undergoing the transforma- 
 tion or, one might almost say, the special fermentation which ends 
 in their caseation. 
 
 There still remains pigmentary degeneration, characterized by a 
 transformation of the protoplasm. It should not be confounded 
 with pigmentary infiltration due to a simple accumulation of pig- 
 ments transported to the cell. The difference here is the same as 
 that between fatty degeneration and fatty infiltration. 
 
 A sclerotic degeneration is also often spoken of. This is the process 
 which has already been described as a mode of repair, a true cica- 
 trization. Connective tissue develops in order to replace the cells 
 that have degenerated or disappeared. The cicatrized tissue is some- 
 times infiltrated with calcareous salts : this process is known as cal- 
 careous degeneration. 
 
326 INFECTIOUS DISEASES. 
 
 Causes of Cellular Degenerations. Although degenerations differ 
 
 in their anatomical and clinical expression and occur under condi- 
 tions peculiar to each of them, and also have a dissimilar significance 
 and evolution, the numerous varieties above described are, never- 
 theless, related by analogous etiological and pathogenic conditions. 
 
 Cellular degenerations always express some nutritional distur- 
 bance. The latter may depend upon three distinct causes: 1. Defi- 
 cient supply of materials destined for nutrition; 2, vitiation of the 
 interstitial plasma — i. e., an intoxication disturbing nutritive metab- 
 olism: 3, disturbance or suppression of the functions of the cell. 
 
 At the head of the first group is naturally placed starvation. It 
 has been demonstrated by a great number of observations and experi- 
 ments that suppression of alimentation is speedily followed by cellu- 
 lar degeneration, under the form of fatty metamorphosis. 
 
 The same results are observed when the blood is altered, either 
 because it no longer brings to the cells a sufficient amount of aliment 
 or because it is not charged with the requisite quantity of oxygen. 
 The former condition is realized when the blood mass is lessened, for 
 example, as the result of profuse hemorrhages ; the latter occurs when 
 the blood corpuscles are altered or decreased in number, to wit, when 
 a local or a general anemia exists. 
 
 It is stated that accumulation of carbonic acid produces the same 
 effect as inadequate supply of oxygen, and this explains the occur- 
 rence of degeneration in cases of venous obliteration or cardiopul- 
 monary insufficiency. In this case, however, the process is rather 
 one of intoxication, and we are thus led to the consideration of our 
 second group. 
 
 It is known that a great number of mineral poisons give rise to 
 cellular degenerations. It will suffice to mention arsenic and espe- 
 cially phosphorus. 
 
 The same is true of cases of endogenous intoxication. Whether 
 the question be one of noxious products developed under the influence 
 of cellular life, or one of substances formed by bacteria normally or 
 accidentally inhabiting our bodies, the result is the same. Let us 
 assume, for example, the condition to be one of increased gastro- 
 intestinal putrefaction; as a result of the absorption of excessive 
 amounts of toxins formed, a degeneration of the hepatic and renal 
 cells will occur, and this may prove to be the beginning of a cirrhosis 
 or a nephritis. A good many cases of Bright 's disease are due to no 
 other origin. 
 
CELLULAR DEGENERATIONS. 
 
 What is done by the toxins of putrefaction i more fully realized 
 by the toxins of pathogenic agents. The numerou varieti* 
 degeneration above described are encountered in the eour e oi infec- 
 tious diseases from cloudy swelling to teato i . coagulation i. 
 sis, and amyloid degeneral ion. 
 
 We have stated thai degeneration may be referable to uppr< wion 
 or disorder of cellular activity. An important distinction musl be 
 in (rod i iced at this point, [n cases of simple lack of function atrophy 
 occurs, but not degeneration. The muscles of an individual who 
 remains inactive diminish simply in volume; when, for instance, a 
 limb is placed in an immovable apparatus, il atrophies bul does uol 
 degenerate. The same is true of glands which remain a1 rest. On 
 the other hand, degeneration is produced when lack of activity 
 results from functional disturbance. It' a muscle or a gland remains 
 at rest because its nutrient vessels are altered or because the nervous 
 cells controlling the functions or the nerves transmitting the impulses 
 are affected, it is not atrophy bul degeneration thai occurs. Thus, 
 section of a nerve does not act upon the muscle through the immo- 
 bility resulting therefrom; the phenomena are more complex — the 
 necessary stimulus is suppressed and degeneration seems again if be 
 connected with a trophic disturbance. 
 
 Without wishing to even briefly study the different varieties 
 degenerations, it may be well to give some complementary informa- 
 tion concerning those most frequently encountered and which have 
 thus far only been alluded to: fatty degeneration and amyloid degen- 
 eration. We shall then present some considerations relative to pig- 
 mentary degeneration. 
 
 Fatty Degeneration. 
 
 Fatty degeneration or steatosis is essentially characterized by a 
 fatty transformation of the nitrogenous substance which enters into 
 the constitution of anatomical elements. As already stated, this 
 should be carefully distinguished from fatty infiltration, which is in 
 reality a cellular obesity. In the latter case fat is stored up in the 
 cellular membrane and, in order to make room for it, the protoplasm 
 is slightly pushed aside. There is addition of a new substance, and 
 not metamorphosis of one already existing. 
 
 Fatty degeneration may be established at once or follow another 
 variety, such as granular degeneration, cloud} - swelling, or albumin- 
 ous infiltration. Under the microscope, in specimens fixed by means 
 
328 INFECTIOUS DISEASES. 
 
 of osmic acid, fat appears in the form of small, black granules, 
 isolated or united in masses, and particularly profuse around the 
 nucleus. This steatosis is frequent in the liver, kidneys, myocar- 
 dium, and muscles. It originates under the most varied conditions. 
 Nutritive disturbances caused by high temperatures are considered 
 important etiological factors, and are supposed to explain the fre- 
 quency of steatosis in infections. It should be remarked, however, 
 that in this instance the problem is a highly complex one, since 
 i he alterations maybe more easily accounted for by a production 
 of toxins than by thermal elevation. Nevertheless, the latter 
 pathogenic condition may also be taken into account, because fatty 
 degeneration has been induced experimentally in animals whose 
 temperature was raised by prolonged confinement in an oven. 
 The alteration is supposed to be due to a lack of oxidation, since, 
 under the influence of high temperature, the red blood corpuscles 
 take up less oxygen than under normal conditions. 
 
 The same explanation may be applied to other etiological condi- 
 tions. The steatosis manifesting itself in the course of infections and 
 poisonings may be attributed to deficient oxidation. 
 
 Finally, steatosis occurs when an organ is rendered inactive in 
 consequence of suppression of nervous excitation, because metabo- 
 lism does not progress in a normal manner. Nervous influence is 
 indispensable for the regular performance of nutrition. When this 
 influence fails, oxidation diminishes and fatty degeneration is pro- 
 duced. The more active an organ is, the greater are its demands 
 for oxygen; consequently, if the supply of this gas be diminished, 
 degeneration will first affect those parts which manifest the greatest 
 physiological activity. Among the muscles the myocardium is first 
 attacked, then the diaphragm ; among the glands, the liver and the 
 kidneys. 
 
 It is not superfluous to note that steatosis occurs when there is 
 diminution but not suppression of oxidations. Stricture of an artery 
 gives rise to fatty degeneration; its obliteration, if not partially com- 
 pensated by collateral circulation, results in necrosis. Suppression 
 of oxidation ends in the death of the cellular elements. 
 
 Amyloid Degeneration. 
 
 Amyloid degeneration was described by Rokitansky (1842) under 
 the name lardaceous degeneration, by Christensen (1844) under the 
 designation waxy degeneration. Virchow (1853) gave it the name 
 
OELLULA i: DEGENERATIONS. 329 
 
 it now bears. In 1858 and LS59 Kekule and Schmidl showed 'lint 
 amyloid I issue is not, as mighl be assumed, an amylaceou ubstance ; 
 
 it is :in albuminoid /. c., ;i nitrogenou lib tance. 
 
 In whatever locality ii may be found il i recognized by mean 
 of certain very simple reactions. Under the influence of the iodo- 
 iodide test it gives a mahogany-red color, which becomes violet-red 
 on addition of sulphuric acid. On contacl with methyl-violel i' 
 becomes red. 
 
 Amyloid substance is perhaps normally mel with in certain parte 
 of the organism. II often constitutes an epiphenomenon in the 
 course of the most varied affections, notably of nephritis. In certain 
 cases it may be so widely distributed thai amyloidism i- the prin- 
 cipal phenomenon. Cohnheini has reported cases in which amyloid 
 degeneration invaded the organism withoui any cause to explain this 
 alteration. Such an event is exceptional. Amyloid degeneration 
 nearly always occurs in the course of infectious diseases that are 
 liable to induce cachectic conditions, such as tuberculosis, syphilis, 
 and multiple suppurations. 
 
 Tuberculosis stands at the head of the list. Amyloidism is com- 
 monly observed in patients who have pulmonary cavities, extensive 
 lesions of the intestine, articular or osseous suppurations, necrosis, 
 and caries. The foci nearly always communicate with the exterior. 
 Next comes syphilis, particularly inherited syphilis. The spleen is 
 the organ chiefly affected. Suppurations of long standing may also 
 give rise to amyloid degeneration. Sometimes arthropathies or 
 osseous suppurations; at other times visceral abscesses, dilatation of 
 the bronchi, or multiple abscesses of the skin, are the causative fac- 
 tors. Lastly, among the rarer causes, Ave may cite cancer, especially 
 ulcerated cancer, and malaria. 
 
 This etiological multiplicity shows that individuals of all ages may 
 be attacked. Amyloidism, however, is particularly frequent among 
 men and at the middle period of life, viz., between twenty and 
 thirty years. 
 
 Animals are not exempt from this degeneration. As in man. it 
 is encountered in tuberculosis and chronic suppurations. Krawkow 
 succeeded in producing it experimentally. It is constantly observed 
 in tubercular pheasants, in the livers of which the tubercles are 
 surrounded by a zone of connective tissue infiltrated with amyloid 
 substance. 
 
 It is at present universally agreed that amyloid matter should be 
 
330 INFECTIOUS DISEASES. 
 
 classed as of nitrogenous origin, hut the mechanism presiding over 
 its formation is as yet unknown. Wagner holds this substance to 
 be intermediate between albumins and fats, and this would explain 
 the frequent coexistence of amyloid and fatty degenerations. Reck- 
 linghausen believes a homogeneous matter is exuded from the cells 
 which coagulates on contact with the interstitial fluids. In the 
 opinion of Ziegler, the diseased cells are unable to utilize the albumins 
 escaping from the vessels; hence the albumins undergo a special 
 metamorphosis. 
 
 At all events, it is certain that amyloid degeneration is closely 
 related to fatty degeneration, since it is produced under the same 
 conditions, and must, therefore, be considered as connected with dis- 
 turbance of albuminous nutrition. 
 
 Amyloid degeneration affects the vessels and the connective tissue 
 in a predominant if not an exclusive manner. In the arteries it 
 begins in the inner coat, sparing the endothelium; it is especially 
 marked in the middle coat. It extends to the capillaries, which it 
 transforms into vitreous, homogeneous tubes lined with epithelial 
 cells which remain intact. 
 
 When it affects the organs it appears in three different macroscopic 
 forms. The whole or the greater part of the organ is invaded; the 
 tissue becomes homogeneous, semitransparent, and larclaceous. At 
 other times the process is limited to small foci presenting the appear- 
 ance of sago grains. Finally, the lesions may be minute and recog- 
 nizable only under the microscope or by transmitted light in thin 
 sections treated with the usual reagents. 
 
 The liver, which is the organ most frequently attacked, becomes 
 considerably enlarged; it appears pasty, larclaceous, and almost 
 bloodless. Under the microscope, infiltration of the capillaries, 
 the hepatic artery, more rarefy, of the portal vein, is found. As to 
 the changes in the hepatic cells themselves, discussion is still open. 
 Some authors assert that degeneration occurs; others contend that 
 the vitreous masses encountered are not altered cells, but amyloid 
 masses exuded from the vessels. 
 
 The localization is analogous in the other organs. In the spleen 
 it is mainly deposited in the Malpighian corpuscles. In the kidneys 
 it is found in the vessels, glomeruli, connective tissue, and the walls 
 of the uriniferous tubules. The epithelial cells are often altered, but 
 never amyloid. We may also mention the amyloid degeneration 
 occurring in the lymphatic glands, in the intestinal mucous mem- 
 
CELLULAR DEQENEBA TI0N8. 331 
 
 brane, and the heart, where the mu cle cells may be involved 
 
 (Letulle and Nicolle). 
 
 When amyloid degeneration is localized it does nol vlw 
 any special disturbances. Thus, in parenchymatous nephritis, in 
 which it is almosl constant, H is qo1 expressed by any appreciable 
 manifestation. 
 
 When ii is extensive i1 produces a certain oumber of phenomena 
 which vary according to its predominance in thif or thai organ. The 
 first indications are paleness of the pal ienl paleness of the skin and 
 mucous membranes and loss of strength. Examination of the 
 abdomen reveals considerable hypertrophy of the liver and spleen; 
 diarrhea is of frequent occurrence; the urine is remarkable for its 
 abundance, pale color, and the greal amounl of albumin which it 
 contains, at least in certain cases. 
 
 Though a Fatal termination is the rule, recovery is possible. The 
 patient overcomes the cause that has produced the degeneration, and 
 the latter subsides and finally disappears. Cohnheim, who has laid 
 stress upon this evolution, cites the following experimeni : Fragments 
 of amyloid tissue when introduced into the peritoneal cavity of an 
 animal are rapidly absorbed. According to him, it must be conclui led 
 that absorption of this substance may occur in the human organism. 
 This experience is interesting, since amyloid matter is very resistant. 
 It is not altered when submitted to artificial digestion with pepsin 
 and hydrochloric acid. Indeed, these are the means generally em- 
 ployed for its preparation. 
 
 Pigmentary Degeneration. 
 
 There are cases of simple pigmentary infiltration and cases of ] lig- 
 mentary degeneration. The cells may be charged with coloring- 
 matters, particularly the leucocytes, which are often loaded with 
 carbon, even under normal conditions. In other cases The cells may 
 be infiltrated with more or less modified blood pigment derived from 
 former hemorrhage. Finally, various black pigments, apparently 
 derived from the blood, may accumulate in certain anatomical 
 elements without disturbing their function. In the case of pigmen- 
 tary degeneration, on the contrary, cellular alterations are found 
 which account for the disorders observed during life. 
 
 Pigmentary degeneration, which is chiefly observed in malaria, is 
 essentiallv characterized bv the accumulation within the cells of an 
 
:):)'2 INFECTIOUS DISEASES. 
 
 okra matter (pigment ocre of Kelsch and Kiener, rubigin of Auscher 
 and Lapique), which has the property of turning black under the 
 action of ammonia sulphydrate 3 or blue on addition of potassium 
 ferrocyanide and dilute hydrochloric acid. The latter reaction, which 
 is very sensitive, is currently employed in histology. In preparations 
 thus treated it may be seen that the pigment invades the protoplasm, 
 pushes it aside, atrophies the nucleus and causes disappearance of 
 the latter. All organs are not equally liable to attack. As is always 
 the case, the frequency of the lesions is in proportion to functional 
 activity. The liver is the organ most frequently invaded; next come 
 the kidneys, then the myocardium and the pancreas. 
 
Oil A PTEB XII. 
 GENERAL REACTIONS FEVER. 
 
 Functional Synergies and Morbid Sympathies. Contiguity of Organs. Vascular Con- 
 ncciions. Hole of Kmlioli m I Kile of Humeral Modifications. Nervoui Connec* 
 tions. Fever. Definition. Thermometry and Calorimetry. Mechanism. Ner- 
 vous and Toxic Fevers. SiL'ni lii-.-i hit oi'ri,iii- and Sweating. Feveri b Reaction 
 of the Organism. Hypothermia Produced I.;.- Toxins. Final Hypothermia in 
 Animals. Persistent Hyperthermia in Man. Causet of ilii- Difference. Produc- 
 tion of Heat in l'cMis by Retention. State of Oxidations. The Thermogenic 
 
 Power of 1 lie Blood. liole of (In- Liver, Kidney, Mini I.iihl'- in t Ik- Production of 
 
 Fever. Role of the Muscles and Nervous System. Therapeutic Deductions. 
 Characters of Feverin Some Infections. Semiological Value of the Thermal Course. 
 
 Functional Synergies and Morbid Sympathies. 
 
 The various parts of the system an- so closely unite. I bysynergies 
 that it is impossible for a lesion to remain absolutely local. On 
 
 superficial examination the disturbances may a] (pear to be confined 
 to a part of the organism: in reality, however, it necessarily gives 
 rise to a great number of modifications in the entire economy. Reac- 
 tions may be more or less marked, at times even imperceptible; 
 nevertheless they exist. 
 
 It is highly interesting to investigate the mechanism through 
 which the lesions of an organ affect the rest of the system. 
 
 The connections existing between the various parts of the organism 
 suggest the following classification of the pathogenic processes of a 
 secondary order : 
 
 1. Functional synergies. 
 
 2. Contiguity of organs. 
 
 3. Vascular connections. 
 
 4. Nervous connections. 
 
 Referring for the general study of secondary pathogenic proce -- - 
 to the article which the author has devoted to this subject. 1 he will 
 Consider only their importance in infectious diseases. 
 
 Functional Synergies. As the result of physiological researches 
 and clinical observations, parts which were separated by anatomical 
 
 1 Roger. Les processus pathogeniques de deuxieme ordre. Traite de pathologie 
 generate, published by Prof. Bouchard, Paris. 1899, vol. iii. p. v 
 
334 INFECTIOUS DISEASES. 
 
 study have been united. Thus are formed physiological unities, 
 acting in harmony and working together to insure the same function. 
 For example, the motor cell, the muscle, and the nerve thai unites 
 them represent a whole from the functional standpoint. Pathology 
 agrees with physiology by showing that the alteration of one of these 
 pans effectively influences the others. We cannot, however, expand 
 on these facts, since they present nothing peculiar in infections. When 
 alterations of an organ induce lesions in another the process is an 
 autogenous one which acquires no particular character from the 
 acting cause. Thus, destruction of the cells in the anterior horn of 
 the spinal cord results in atrophy of the corresponding muscular 
 fibres. Here is a striking example of morbid sympathy correspond- 
 ing exactly to a functional synergy. However, whatever the eause 
 that has produced the cellular lesion may be, the muscle will degen- 
 erate. Likewise, when lesions of the liver produce consecutive 
 lesions in the kidneys, the process that has acted upon the hepatic 
 gland imparts no particular character to the renal lesion. It is not 
 superfluous to refer to these facts, for they explain a great variety 
 of symptoms occurring in the course or in consequence of infectious 
 diseases. 
 
 Contiguity of Organs. It will suffice to recall for a moment the 
 anatomical positions and mutual relations of organs in order to 
 comprehend how lesions developing in one of them may mechani- 
 cally affect the others. A purulent focus produced in one part 
 compresses the adjacent parts and produces in them various dis- 
 turbances which may be transitory — i. e., disappear with the lesion 
 which caused them — or may survive it and run an independent 
 course of evolution. 
 
 If the compressing organ is the seat of an inflammatory affection, 
 notably a suppurating or gangrenous lesion, it may, in addition to 
 the mechanical influence, exert a specific action. An inflamed tissue 
 often gives rise to paralysis in subjacent parts. Stokes long ago 
 proved this fact as regards the diaphragm in cases of purulent pleu- 
 risy. Likewise, a phlegmonous angina may cause paralysis of the 
 palate. In certain rare instances an acute pericarditis may produce 
 paralysis of the myocardium. What is produced in the striated 
 muscles is likewise observed in the non-striated; such is the case in 
 gastrointestinal paralysis occurring in peritonitis. 
 
 Are these paralytic phenomena due to the special influence of the 
 inflamed tissue, or are they the result of the action of soluble products 
 
GENERA L REACTIONS FEVER. 
 
 secreted by the pathogenic agenl ? It i at present iinpot ibl< 
 answer these questions. They requin experimental investigatii 
 
 Vascular Connections. By acting upon the heart, disturbing 
 function, altering its tissues, or by creating valvular lesions, infec 
 lions produce profound modification): in the blood circulation, 
 and thus give rise to a series of disorder throughout the entire 
 system. 
 
 Role of Embolism, li is through the vascular >-i'in particularly 
 that infectious foci produce lesions in distant parts. Ve -•■]- trav- 
 ersing diseased parts are often obliterated either because microbee 
 penetrate into them or because toxins diffuse and give rise to toxic 
 endarteritis or endophlebitis. The latter hypothesis is supported by 
 the fact that emboli are no1 necessarily infective; they may ad 
 mechanically. It is, therefore, possible to observe fibrinous emboli 
 exuded from an obliterated vein in contact with a purulent focus; in 
 other instance's fatty emboli occur, originating from an a 
 myelitis. 
 
 Besides mechanical emboli, there arc animate one- which have a 
 highly important bearing on our subject, since they account for the 
 extension and generalization of a great number of lesions. Lot us 
 take, for example, actinomycosis. The primary focus may give rise 
 to secondary, sometimes multiple, lesions, which in some cases are 
 sufficiently numerous to suggest pyemia. The same is true of cast e 
 of aphtha; and this result is comprehensible, since AYagner has shown 
 that the oidium sends out prolongations into the vessels of the 
 mucous membrane. In this way is explained the formation of vis- 
 ceral foci, such as have been recorded by Zenker and Ribbert. 
 
 It is in generalization of infectious lesions especially, however, that 
 phlebitis and embolism intervene. Since the researches of Cruveil- 
 hier and Yirchow their role in the production of pyemia is well known. 
 After having colonized in a clot, microbes manifest a stronger ten- 
 dency to disperse and multiply in various organs. In fixing them- 
 selves upon the vessels they seem to be aided by solid particles which 
 serve them as vehicles of transportation. The secondary lesions 
 which they thus create are similar to those of the original focus. 
 Such is not always the case, however. When, for instance, pyogenic 
 microbes derived from a purulent lesion make their way into the 
 lung they produce in the latter organ lesions which are secondarily 
 invaded by the bacteria of putrefaction, and thus is formed a gan- 
 grenous focus. 
 
336 I27FECTI0 l 's DISEASES. 
 
 Emboli generally follow a route 1 traced in advance and governed 
 by the laws of the circulatory mechanics. There are exceptional 
 cases described under the name retrograding or paradoxical emboli. 
 Paradoxical embolism is explained by the persistence of Botal's 
 foramen (Cohnheim, Linen. Zahn). Retrograde embolism is due to 
 cough and effort which disturb the circulation in the inferior vena 
 cava and cause emboli to retrograde in the hepatic and even renal 
 veins (Recklinghausen) . 
 
 Lymphatic emboli should not be overlooked, although less impor- 
 tant than blood emboli. They account for the spread of microbes, 
 and sometimes, especially in the thorax, they may be of retrograde 
 type. These emboli are interesting because they demonstrate the 
 action of the lymphatic glands in cases of visceral lesions and how 
 they, in their turn, may become the source of new lesions. 
 
 The effect of embolism may be immediate or remote. Immediate 
 symptoms are observed in cases of large emboli arrested in the heart 
 or an important vessel. They act mechanically, give rise to numerous 
 and at times very grave and speedily fatal disturbances, due either 
 to vascular modifications or, more frequently, to influences of a 
 reflex order. 
 
 The violent dyspnea and sudden death in cases of voluminous 
 pulmonary emboli are due, I believe, to a true inhibitory action 
 aroused by the excitation of the intrapulmonary terminations of the 
 pneumogastric nerve. 
 
 There are also small, specific emboli. Toussaint attributed to them 
 an important role ; he argued that most of the symptoms caused by 
 the anthrax bacillus are due to embolic obstruction of the capillaries. 
 This view is not acceptable. The study of infections, however, proves 
 that microbes may emigrate through the vessels and become fixed 
 at a certain point. When arrested the pathogenic agent gives rise 
 to no immediate manifestation; secondary lesions, however, which 
 result in the formation of a new focus are produced around it. 
 Although the process is designated as microbic embolism, there is 
 no true embolus: the microbes are arrested in a vessel because its 
 walls are altered, and the circulation is consequently slow. Thus, a 
 selective colonization takes place without the sudden and abrupt 
 arrest which characterizes true embolism. Logically, the term in- 
 fectious embolus should be employed when a vessel is suddenly 
 obstructed by a solid particle and notably by a fragment of a clot 
 or valve impregnated with microbes. 
 
GENERAL REACTIONS FEVER. 
 
 Role of Modifications in the Organic Fluids. The Vascular ;. -tern 
 
 may further serve in the development of secondary pal hological pro- 
 cesses by distributing throughout the organi m oluble products or 
 microbic toxins engendered al & certain point. It Is, however, like- 
 wise owing to these vascular connections thai the toxins are broughl 
 to the organs capable of transforming or eliminating them. It U 
 important to note thai the increased work thut imposed upon the 
 glandular cells may give rise to new lesion which, in their turn, 
 become the source of other morbid proce 
 
 Nervous Connections. In the presence of the facts thus far con- 
 sidered there can be no escape from the conviction thai no lesion 
 can remain local. We have not, however, yel taken into accounl 
 the highly importanl rdle of the nervous system, which constantly 
 intervenes to establish solidarity among the various parts of the 
 organism. In the course of a disease the nervous system regulates 
 the formation of inflammatory foci, produces vascular dilatation or 
 constriction, and stimulates or arrests liquid exudations and migra- 
 tion. It also plays an important part in the development of certain 
 symptoms. Let us take cough, for example. In some respects this 
 is a rather favorable disturbance, since its effect is to rid the respira- 
 tory apparatus of secretions obstructing the passages. These secre- 
 tions oppose the penetration of microbes, but their elimination by 
 coughing has the advantage of expelling the pathogenic agents. In 
 order that expectoration may be effected the synergic action of a 
 great number of muscles is required. They are excited to action 
 through reflex influences. The result is the same, however, if the 
 excitant is a poison or some foreign body. The effects resulting from 
 nervous connections possess nothing peculiar in the case of infection. 
 Such is also the case when the microbe or its toxin invades the organ- 
 ism and becomes localized in the nervous system. The functional 
 modifications thus produced acquire no peculiar character from their 
 origin. It is necessary to remark, however, that intoxication of the 
 nervous system may give rise to a great number of functional dis- 
 turbances. In another chapter we shall see that dyspnea, cardiac 
 disorders, vomiting, and even anuria in many cases depend upon 
 intervention of the nervous system and not upon a lesion of the 
 organs affected. In scarlet fever, for example, early anuria is seldom 
 the clinical expression of a renal lesion : it is due rather to a nervous 
 disorder, and, when the latter ceases, we are surprised to find neither 
 albumin nor casts in the urine. 
 
338 INFECTIOUS DISEASES., 
 
 Fever. 
 
 Ft ver is a morbid state resulting from the exaggeration of the 
 chemical processes concerned in the production of animal heat. These 
 chemical processes may be more active and still retain their normal 
 character, or they may differ from those produced under normal 
 conditions. This distinction is of considerable importance from a 
 i hcrapeutic standpoint, but it does not invalidate the definition above 
 given. Whether deviated from their habitual type or not the chem- 
 ical acts are more intense; this is the characteristic of fever. 
 
 The definition which we propose explains the difference between 
 the terms hyperthermia and fever. Hyperthermia (hyperpyrexia) is 
 rise of temperature, whatever the cause. An animal is placed in an 
 oven; its temperature rises 1° or 2°; we then say that this animal 
 presents hyperthermia, but there is no question of fever. Hyper- 
 thermia none the less constitutes the principal symptom of fever. 
 Animal heat indicates the measure of the intensity of organic com- 
 bustion under normal conditions. It, therefore, also indicates the 
 changes which combustion undergoes in pathological conditions. It 
 is intelligible, however, that the results may be modified by increased 
 radiation of heat. For the sake of argument it may be assumed 
 that increase in the production of heat is exactly counterbalanced 
 by increased radiation. The temperature then undergoes no modi- 
 fication. Moreover, if radiation becomes more active it may over- 
 balance the production and, notwithstanding the exaggeration of the 
 chemical processes, the temperature falls. It is thus conceivable that 
 fever may be attended by hypothermia. 
 
 These are only theoretical considerations. In order to appreciate 
 their value it is necessary to complete the indications furnished by 
 the thermometer by means of the calorimeter. The amount of heat 
 lost is thus determined. Knowing, on the other hand, the modifica- 
 tions of the temperature, one may easily calculate the quantity of 
 heat produced. It is precisely this quantity that measures the inten- 
 sity of the chemical phenomena. Fever may therefore be defined as 
 follows, which repeats in another form the definition the author has 
 given above : Fever is a morbid process characterized by increased 
 production of animal heat. 
 
 Unfortunately, while thermometry is easy of application in clinical 
 medicine, calorimetry can hardly be employed in current practice, 
 for it necessitates the use of delicate apparatus and disturbs the 
 
GENERA L REACTIONS— FEVER. 
 
 patient. According to the results of scientific re earche pui ued on 
 this matter, however, discord between calorimetry and thermometry 
 is quite rare and, at all events, of short duration. Therefore, exam- 
 ination of the temperature is generally sufficient. Practically, h be 
 more important to know the heal of the body than the radiation of 
 the calorics, Tor it, is against the modification in plus or in minuf ol 
 animal heat that the physician has to fight. The thermometer alone 
 furnishes him with the necessary indications. 
 
 Classification of Fevers. All infections are nol febrile, nor are all 
 fevers infect ions. 
 
 From the standpoint of pathological physiology, all fever- may 
 be divided into two groups: fevers of Qervous origin and fevers due 
 to intoxication. 
 
 Fevers of nervous origin may he subdivided into three categories: 
 
 First, algic fevers resulting froi 1 1 painful excitation. This is besl 
 illustrated by the so-called hepatalgic fever observed in hepatic colic-. 
 even when no symptom suggests infection of the biliary passages. 
 This fever has been experimentally produced in the dog by means 
 of excitation of the biliary passages. 
 
 The fevers constituting our second group represent a reaction of 
 the organism aroused by hypothermic action. If an animal I >e | /laced 
 in a refrigerator, especially if care be taken to immobilize it, its tem- 
 perature falls. If the animal then be released and placed in a warm 
 locality, the temperature rises and exceeds the normal. The process 
 is surely one of febrile character, for the hyperthermia expresses 
 increased combustion on the part of the animal in order to struggle 
 against the excessive dissipation of heat. 
 
 In the same group may be classed reactionary fevers consecutive 
 to toxic hypothermia. For example, an individual has ingested car- 
 bolic acid; his temperature falls to 95° F. (35° C); a few hours later, 
 however, it rises and reaches 102.2° or 104° F. (39° or 40° C . 
 
 The third variety comprises the febrile movements occasioned by 
 traumatism affecting certain parts of the nervous centres. Their 
 reality has been demonstrated by some observations, notably by a 
 case of meningeal hemorrhage observed in our wards and recorded 
 by Dr. Josue: also by experimental researches, those of J. F. Guyon 
 among others. Hysterical fever may also be classed here. 
 
 Fevers of toxic origin are by far the most important. They also 
 include three varieties. At times febrile movement is consecutive 
 to the introduction into the organism of completely formed toxic 
 
340 IXFECTIO US DISEASES. 
 
 substances proceeding from without. The number of hyperthermiz- 
 ing substances is quite restricted. We may cite strychnine and 
 cocaine. At other times fever is due to autointoxication, and, finally, 
 to microbic intoxication. 
 
 The reality of fevers due to autointoxication has been demon- 
 strated by numerous experiments and rigorous clinical observations. 
 "With this group should be classed the fever of gouty and chlorotic 
 patients, the fever consecutive to the absorption of traumatic san- 
 guineous exudates and to attrition of tissues, certain forms of fever 
 due to overexertion, and the fever of asphyxia, 
 
 The fevers of microbic origin evidently constitute the most impor- 
 tant group. As has already been stated, however, infections are not 
 always pyrogenic. Chronic diseases, such as syphilis, may evolve 
 without being attended by any elevation of temperature. The beha- 
 vior of a given infection may altogether differ from one individual 
 to another. Unquestionable observations of apyretic typhoid and 
 scarlet fevers have been published. Apyretic erysipelas is not of 
 uncommon occurrence. Habitually pyrogenic infections, such as 
 pneumonia, are in certain cases attended by subnormal temperature. 
 These well-known facts lead us to the admission that the role of the 
 organism is vastly more important than that of the microbe in the 
 production of fever. We shall see that this idea is confirmed by 
 numerous experiments. 
 
 It must be recognized, however, that the great majority of acute 
 and even some chronic infections are accompanied by fever and 
 hyperthermia. Are the fever and hyperthermia due to microbic 
 toxins? Experimentation seems to answer affirmatively. The injec- 
 tion of sterilized cultures into animals produces not only hyper- 
 thermia, but true fever, with all its modifications in chemical pro- 
 cesses. The problem is, however, more complex than appears at first 
 sight. All substances capable of affecting the temperature produce a 
 primary action followed by a secondary reaction of a reverse charac- 
 ter. In most cases the latter is not intense ; it may, however, especially 
 in infections, be more pronounced than the primary phenomenon 
 and appear so rapidly as to completely mask the primary action. 
 
 The questions confronting us, therefore, are: Does fever result 
 from a microbic action? Does it, on the contrary, represent a reac- 
 tion of the organism against the action of the microbe which tends 
 to produce hypothermia? The latter conception seems to us most 
 in harmony with experimental facts. 
 
GENERAL REACTIONS /'/■- vi.i:. 3 1 1 
 
 Let us first consider the primary element of a greal number of 
 febrile processes i. r., chilU. At present we know thai chills repre- 
 sent a means of getting warm when the body is cold. Accordii 
 the hypothesis that toxins directly produce fever, It would l"' m 
 sary to admit that they are capable of directly stimulating the nerve 
 (■en 1 res eoneerneil in the production of chills. This might be possible, 
 but nothing proves it , and the easier study of ordinary chills reveals 
 no similar fact. II may be objected that chills generally appear 
 when the central temperature has already begun to rise. Thie result 
 simply proves that the organism began to react against the hypother- 
 mizing action of toxins, but thai its reaction was insufficient . and for 
 that reason it had recourse to chills, which represenl a rapid pr< 
 of producing heat. 
 
 A febrile paroxysm ends by profuse sweating. From the stand- 
 point of thermal regulation, perspiration represents the reverse of 
 chills. It is a means employed by the organism for lowering its 
 temperature. Now, if fever is directly produced by microbic toxins, 
 why does not perspiration appear sooner? This would materially aid 
 the organism to combal the hyperthermizing action of toxins. If, 
 on the contrary, we admit that fever is an expression of a reaction 
 on the part of the organism, it is readily conceivable that it is no 
 longer of any use when the action of toxins ceases. The sweats do 
 not appear from the first, because the organism is struggling against 
 a hypothermizing substance; as soon, however, as the action of the 
 latter ceases, reaction is useless and perspiration begins. 
 
 If microbic toxins are hypothermizing, why does the temperature 
 rise above the normal? It would seem that the organism should react 
 only with energy sufficient to keep the bodily heat at its habitual 
 level. In reality, the reactions of the organism are not always meas- 
 ured to the salutary effect. They often exceed the end, and, from 
 this point of view, reaction is, in the present case, too intense. It 
 has not been demonstrated, however, that this exaggeration of the 
 process is useless. 
 
 Reasoning thus leads us to the assumption that fever is a reaction 
 of the organism. It will now be seen that experimentation gives 
 considerable support to this theory. 
 
 Action of Microbic Toxins upon Temperature. Microbic toxins 
 possess the property of exciting fever when injected in small amounts : 
 when introduced in large doses they lower the temperature. The 
 experiments of Sanarelli with the typhoid toxin, those of Metchnikoff 
 
342 
 
 IXFECTIOUS DISEASES. 
 
 with tin' toxin of hog-cholera are, from this point of view, demon- 
 strative. The author obtained a similar result with the toxin of the 
 colon bacillus. This toxin is said to be hypothermizing; in fact, that 
 is what occurs when large doses are injected. When, however, small 
 amounts are introduced, organic reaction takes place and the tem- 
 perature rises. A glance at Fig. 15 will show that a dose of ten drops 
 produces a thermal rise of 1° or 1.5° C, which persists for five or six 
 hours. 
 
 A very small dose, not exceeding half a drop, gives rise to a more 
 intense, at least more rapid, febrile movement. On the other hand, 
 
 Fig. 15. 
 
 
 |?i 
 
 ll» 2 3 4 
 
 ■■ 
 
 G 
 
 3 
 
 105.8° 
 
 ioe 
 
 cr 
 102.2 
 
 Q. 
 
 s 
 1- 
 
 lOO.i' 
 BS.6° 
 9C.S C 
 
 
 
 
 
 
 
 
 ^R 
 
 
 
 
 
 
 
 / 
 
 v V 
 
 
 <^5 
 
 
 
 
 1 
 
 v ^ 
 
 ■" 
 
 \ 
 
 
 
 
 te 
 
 y 
 
 s 
 
 
 
 V 
 
 
 If 
 
 
 
 
 
 \ 
 
 
 —l\I— 
 
 
 
 
 
 \ 
 
 
 li 
 
 
 
 
 
 \ 
 
 3T 
 
 
 
 
 
 
 
 \ 
 V 
 
 
 
 
 
 
 
 
 ni /v 
 
 
 
 y\ 
 
 
 
 
 \ 7 ^^^ 
 
 
 
 
 
 \ / 
 
 
 
 
 
 
 
 V 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 | 
 
 
 
 r 
 
 
 
 
 
 
 : 1 
 
 
 
 
 
 1 1 1 
 
 
 
 
 
 
 
 i 
 
 
 
 
 Action of the colon bacillus toxin upon the temperature. I. Injection of 0.025 c.cm. of 
 toxin into a vein. II. Injection of 0.5 c.cm. III. Injection of IS c.cm. 
 
 large closes tend to lower the temperature — their first effect is to 
 hypothermize ; the organism then reacts, and the temperature rises. 
 It remains close to the normal and then rapidly falls at the moment 
 of death. 
 
 The theory which I advocate likewise explains the differences 
 observed in the variations of temperature according to the mode 
 of introduction of the toxin. If a large dose is injected into the 
 veins or the peritoneum, absorption is rapidly effected, and the 
 
GENERA L BEA< 'TIONS FEVER. 
 
 343 
 
 temperature falls until the momenl of death. It the same amount 
 is deposited in the subcutaneous cellular ii- ue , absorption being 
 slower, the organism has time to react; the temperature a1 first 
 rises, to undergo a subsequenl fall. 
 
 I have found the same differences by introducing the toxin of the 
 colon bacillus by a peripheral vein and by a branch of the portal 
 vein. In the latter instance the poison passes through the liver, 
 which possesses the power of arresting and neutralizing a pari 
 of it. Two rabbits of nearly equal weight received each 20 c.cm. 
 
 Fio. 18. 
 
 
 
 hi 
 
 1 
 
 2 
 
 3 
 
 1 I •"> 7 8 
 
 100.8 
 
 104° 
 
 GC 
 
 I 
 
 108.2° 
 
 CL 
 
 2 
 
 100.1° 
 0S.6 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 A 
 
 
 
 
 
 • X 
 
 
 
 
 
 
 
 
 
 -X- 
 
 \ 
 
 
 
 
 
 5b 
 
 
 Y \ 
 
 \ 
 
 
 
 
 
 ^M 
 
 > 
 
 \ 
 
 
 
 L/ 
 
 
 
 
 \ 1/ 
 
 \\ 1 1 \ 
 
 
 \ \ 
 
 
 
 \ 
 
 
 \v ' 
 
 
 
 
 1 
 
 
 \* t 
 
 
 
 
 1 
 
 
 \\j 
 
 
 
 
 
 \ I 
 
 
 _i 
 
 
 
 
 
 \ 
 
 
 
 
 
 
 
 H 
 
 
 
 
 
 
 
 
 " DEATH 
 
 
 i fc> HOUR L-TER 
 
 Influence of the liver upon febrile reaction. A. Injection of 20 c.cm. of toxin by the 
 portal vein. B. Injection of 20 c.cm. of toxin by a peripheral vein. 
 
 of slightly attenuated colon bacillus toxin. In order to render 
 the results comparable, both rabbits were bound for about half 
 an hour to the experiment plank, and the one which received 
 the poison by an auricular vein was subjected to a laparotomy. 
 The two animals were thus placed, with a view to the thermal 
 reactions, under absolutely identical conditions. As soon as the 
 animals were released the temperature in both was found lowered 
 by 1.5° C. From that moment on, however, the temperature rapidly 
 rose in the animal injected by the portal vein (A, Fig. 16), and 
 
344 INFECTIOUS DISEASES. 
 
 exceeded the normal by 2° C. In the other (B, Fig. 16) it first 
 continued to fall, then rose to its initial figure, to again fall rapidly 
 at the moment of death. This animal succumbed at the end of 
 seven hours and a half; the other — the one which received the toxin 
 by a branch of the portal vein — died only at the end of four days. 
 
 Similar differences are observed according as the experiment is 
 made upon susceptible or refractory animals. By inoculating 
 anthrax into vaccinated chickens, dogs, or rabbits, fever may be 
 produced; while in animals which succumb to the infection, hyper- 
 thermia soon gives way to hypothermia. 
 
 In the same order of ideas may be cited the experiments of Gam- 
 aleia, which prove the thermogenic action of cultures to be in inverse 
 ratio to their virulence. Thus, for example, the second vaccine of 
 anthrax bacillus, which kills the rabbit in three days, first produces 
 a rise in temperature, reaching 105.8° F. (41° C); while an exalted 
 culture which kills the animal in six or eight hours causes no hyper- 
 thermia. I have reached a similar conclusion by employing, not 
 living cultures, but toxins. Two cultures of the staphylococcus 
 aureus were prepared, one with a specimen of moderate virulence, 
 the other with the same specimen considerabty exalted by means 
 of successive passages. The cultures sterilized by means of chloro- 
 form were then injected into two rabbits. One of them (B, Fig. 17) 
 received 5 c.cm. of the toxin obtained from the exalted microbe. 
 It succumbed at the end of four hours and a half in hypothermia. 
 The other (Fig. 17) received 20 c.cm. of the culture made with the 
 attenuated microbes. The temperature rose from 103.2° F. to 
 105.8° F. (39.5° to 41° C), and forty-eight hours later the animal 
 was still living. Its temperature then had fallen to 101.1° F. 
 (38.4° C). Another injection of 20 c.cm. of the same toxin was 
 given. This time the temperature showed no modification. In 
 this organism already exhausted by a first intoxication reaction was 
 no longer possible, and, in fact, the animal was found dead the 
 following morning. 
 
 This experiment shows that an animal weakened by a previous 
 injection is no longer capable of developing fever. The result would 
 be absolutely incomprehensible if fever was held to be the result of 
 the action of the toxin; it becomes very clear, however, when it 
 is considered as a reaction of the organism. This experimental fact 
 elucidates certain clinical observations. It explains why cachectic, 
 exhausted individuals develop no fever on the occasion of an infec- 
 
GENERAL REACTIONS /•'/•; I I E 
 
 346 
 
 tion. [t likewise accounts for the fad thai an intercurrenl infection 
 supervening in an individual already i i (, k may lower the temperature 
 instead of raising it. This is whal occurs, for example, in certain 
 cases of pneumonia developing in the course of a typhoid fever. 
 The organism, already saturated with the typhoid toxin, if unable 
 bo struggle againsl the effects of a new toxin; therefore, instead of 
 rising, as in a healthy individual, the temperature falls. 
 
 By another series of experimental infection- we observed thai 
 the genera] state of the animals remains quite satisfactory ae long 
 as fever lasts, and thai aggravation of the symptoms coincides with 
 the fall of temperature. 
 
 Fig. 
 
 
 lal Hay 
 
 2d Dmjr 
 
 :..! Us, 
 
 105.8 
 
 101 
 
 I 
 < 
 
 102.2° 
 
 o! 
 
 E 
 
 h 
 
 100. i° 
 98.6° 
 
 M' i 
 
 i'' 
 
 2 
 
 a|, 
 
 22'' 
 
 H&ua 
 
 lh 
 
 a l 
 
 
 
 
 
 
 
 1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 a/ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 B!_ 
 
 
 
 
 
 
 
 
 
 
 \ 
 \ 
 
 ft 
 
 
 OE'Tm 
 
 
 
 
 
 
 \ 
 
 /\ 
 
 3 
 
 
 
 
 
 
 
 V » 
 
 
 LATI / 
 
 
 
 
 
 
 
 \ 
 
 
 , 
 
 
 
 OE.Th 
 
 
 1 
 
 
 P 
 
 
 
 
 THE FIEXT 
 
 
 
 \ 
 
 1 
 / 
 
 
 
 
 
 MO 
 
 MUG 
 
 
 
 \ > 
 
 ' 
 
 
 
 
 
 
 
 
 
 \> 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 1 
 
 
 
 
 
 
 Action of staphylococcic toxin upon temperature. A. Intravenous injection of 
 20 c.cni. of a moderately active toxin; a similar injection on the third day. B. Intra- 
 venous injection of 5 c.crn. of an active toxin. 
 
 In man the course of temperature is in general different : in the 
 great majority of acute infections death supervenes in the midst 
 of hyperthermal phenomena. Algid collapse is seldom observed at 
 the end of diseases. The reason resides in the fact that man suc- 
 cumbs before having exhausted all his resources: the animal dies 
 when it is absolutely incapable of struggling against infection, when 
 its reactionary power is completely extinct. Such is not the ca.se 
 with man, because his more sensitive nervous system is sooner 
 poisoned. In the animal the subordinate tissues, the organs of 
 secondary importance, succumb almost simultaneously with the 
 
346 ISFECTIO US DISEASES. 
 
 nervous system: at The approach of death general nutrition is 
 hindered, chemical actions are on the decline, and the temperature 
 is falling; the mammalian is thus practically transformed into a 
 cold-blooded animal. When a moribund animal is killed, red blood 
 is found in its veins and right heart. Even the tissues are found 
 modified in the very same manner as in animals artificially subjected 
 to cold. The nervous system of man cannot accommodate itself 
 to the same unfavorable conditions as that of the animal. It dies 
 while the other tissues are still in full activity, and the chemical 
 actions still keep its temperature above the normal level. 
 
 In certain instances, however, human infections lower the temper- 
 ature. Such is the case in cholera and choleriform enteritis. Such 
 is likewise the case in very acute infections, in certain septicemias 
 consecutive to major surgical operations, and the evolution of which 
 resembles that of traumatic shock. Under these conditions the 
 organism is rapidly overwhelmed and incapable of reacting ; accord- 
 ing to an expression of Weber, the patient dies in chills and fever. 
 
 This result is in perfect harmony with the experimental facts 
 above related. It demonstrates that fever is not produced except 
 when the organism is still able to react. 
 
 Mechanism of Fever. Let us now inquire as to what this reaction 
 consists in: does it reside in increased production of heat or in the 
 retention thereof? Both hypotheses have their advocates. Certain 
 experiments, notably those of Rosenthal and Maragliano, demon- 
 strate that during the stage of initial rise the radiation of heat 
 diminishes — a fact which is strictly in accord with those above re- 
 ported. At the beginning of the febrile movement, when the central 
 temperature is already rising, the peripheral is below the normal; 
 it is at that moment that chills are called into play. Then both 
 temperatures rise, but not with the same rapidity, so that the differ- 
 ence between the central and the peripheral temperature may at 
 times amount to 18° F. (10° C). The dissipation of heat during 
 the stationary period is equal to or greater than the normal. In 
 cases of transitory febrile paroxysms the dilatation of the cutaneous 
 vessels, which augments the radiation of heat, is produced before 
 defervescence. In cases of prolonged fever there is increased radia- 
 tion throughout the stationary period. 
 
 It results from these facts that, even if there is a retention of 
 caloric at the beginning of a febrile movement, it is exaggerated 
 production that characterizes the stationary period. The losses 
 
GENERAL REACTIONS FEVER. :;I7 
 
 being greater, the higher temperature musl be due to exaggerated 
 production. Ii is to be noted, however, thai the increa e in radia- 
 tion of heal is not proportional to the increase in H production; 
 
 hence there is partial relent ion df the heal produced. 
 
 It may now he asked whether there i b simple increase of the 
 normal chemical processes or a deviation from t he physiological type. 
 
 In order to solve this problem, the excrementitious products 
 eliminated by the respiratory or urinary apparatus -hould be 
 analyzed. 
 
 Some authors, studying the gases of respiration, noted an increase 
 in the exchanges. WCitheim, on the other hand, ie of ;i different 
 opinion. Less oxygen is absorbed, and on this point he is sup- 
 ported by ITenrijean's investigations. The :iinoimt of carbonic acid 
 likewise undergoes a diminution. The contrary result is due. accord- 
 ing to Senator, to the fact thai the elimination of this gas is more 
 complete as a result of the acceleration of the respiratory move- 
 ments and diminution of the alkalinity of the blood. 
 
 Dr. Robin has reached conclusions which seem to harmonize the 
 dissimilar results above reported. He carefully distinguishes plain 
 inflammatory infectious states from grave typhoid conditions. In 
 the former instance oxidations are at times normal, oftener more 
 active; they are diminished in the latter. This distinction elucidates 
 not only the modifications in the gaseous exchanges, but also the 
 variations observed in the composition of the urine. The urea is 
 increased, often from 50 to 100 per cent. (Unruh, Senator), in acute 
 cases; while in grave typhoidal states and in fevers of long duration 
 the amount decreases; the extractive matters are then found to be 
 augmented. Probably the alterations developing in the cells, 
 notably in those of the liver, prevent the normal elaboration of 
 the products of dissimilation. These are produced in excess, a fact 
 which accounts for the thermal elevation, but are rejected before 
 having undergone their complete evolution. Finally, the disturb- 
 ances of the respiratory function seem to be the main cause of the 
 excess of uric acid so often observed in the urine of those suffering 
 from fever (Ranke). 
 
 Thus fever is due to increased chemical activity, whether or not 
 there be concomitant departure from the normal evolution of matter. 
 Dissipation of heat in fever is more marked than under normal con- 
 ditions, but excess in production of heat is still more marked, hence 
 the relative retention of caloric and rise in temperature. 
 
348 IXFECTIO US DISEASES. 
 
 Role of the Blood in Thermal Regulation. The first question is 
 whether the blood is pyrogenic in animals suffering from fever. In 
 this investigation the action of normal blood upon the temperature 
 must previously be determined. The writer has pursued a series 
 of very delicate experiments which are yet in part unpublished and 
 which have led him to some definite conclusions concerning this 
 subject. 
 
 Blood taken from the carotid artery of a rabbit was injected into 
 the auricular vein of another animal of the same species, care being 
 taken to operate with extreme rapidity, in order to prevent, as far 
 as possible, the modifications which are easily produced in blood 
 outside the vessels. The blood of a dog, taken under the same 
 conditions, was injected in the same manner. The experiment was 
 also made with defibrinated blood. 
 
 Two opposite results were obtained. There occurred a slight 
 diminution of temperature when total blood was introduced into 
 a vein, varying from one-tenth to four-tenths of a degree Centigrade. 
 There was a marked rise of temperature when the same blood was 
 injected defibrinated, the hyperthermia thus produced varying from 
 half a degree to one degree Centigrade. Defibrinated blood acts as 
 the extracts of tissues; in some cases, however, the hyperthermia 
 which it causes is preceded by a slight hypothermia. The blood 
 serum acts like defibrinated blood. 
 
 Several hypotheses may be advanced to explain these strange 
 differences which are observed according as total or defibrinated 
 blood is injected. 
 
 Defibrinated blood is considered by many authors as a fluid in- 
 capable of serving for the nutrition of the organism. To inject it 
 into the veins would mean to introduce a toxic substance, and the 
 febrile movement resulting would then be intelligible. Recent 
 experiments of Dastre have demonstrated, however, that defibrin- 
 ated blood is perfectly adapted for supplying the needs of the 
 economy. An animal may be bled, and its defibrinated blood may 
 again be introduced into its circulation without any serious dis- 
 turbance. 
 
 The marked instability of organic matter may suggest the supposi- 
 tion that blood becomes thermogenic simply because it has been in 
 contact with air or because it has been kept for a while outside the 
 vessels. With a view to verify this hypothesis we received a certain 
 amount of blood in a vase covered with vaseline. As Freuncl has 
 
GENERAL REACTIONS FEVER. .;i:> 
 
 shown, under these conditions coagulation i- notably retarded. At 
 the end of half an hour the Mood, which was perfectly liquid, 
 injected into the veins; ii produced aslighl hypothermia like the 
 
 normal blood. 
 
 II, may be supposed thai the hypothermizing power of total blood 
 is due to the presence of fibrinogenic substance] the latter, becoming 
 insoluble, allows an antagonistic substance to act. Thi hypothesis 
 is also contradicted by fuels. For the production of thermal eleva- 
 tion it suffices to injeei a liquid containing some fibrinogenic sub- 
 stance, for example, the fluid of pleurisy or of hydrocele. The 
 serosity of pleurisy acts, then, like the bloodserum. h firsl Induces 
 a slight hypothermia, and subsequently raises the temperature. 
 Hayein 1 likewise obtained hyperthermia by injecting hydrocele fluid 
 into the veins of a dog. 
 
 What is known of ferments is in favor of the assumption thai the 
 thermogenic action is due to the fibrin ferment. Several observers, 
 and notably Prof. Hayem, have conclusively shown thai this fermenl 
 raises the temperature. Since its amount notably increases in 
 defibrinated blood and in serum, it was natural to attribute to it 
 the thermogenic property of these fluids. "When, however, defibrin- 
 ated blood is heated to 140° F. (60° C.) sufficiently long to destroy 
 the ferments, the thermogenic power of this fluid is by no mean- 
 abolished. On the other hand, the results obtained by study of 
 the extracts of blood prepared by means of alcohol or dialysis 
 warrant complete denial of the influence of this ferment. 
 
 The nature of the substances capable of modifying animal heat 
 remains therefore undetermined. The facts simply warrant the 
 conclusion that total blood is slightly hypothermizing. and that 
 defibrinated blood and serum raise the temperature, and sometimes 
 raise it after having first lowered it. 
 
 There exist, however, certain cases in which arterial total blood 
 is thermogenic, for instance, when the animal which furnishes the 
 blood is sick or when it is submitted to the action of cold. It is 
 not even necessary that the central temperature be lowered in order 
 to render the arterial blood thermogenic. Several times animals 
 that had stayed outdoors in cold winter days furnished the blood 
 which raised the temperature of the transfused animals. It suffices 
 to keep the animal in a well-heated room for twenty-four hours 
 to cause the new property to disappear. 
 
 1 Hayem. Du saug. Paris. 1SS9. p. 239. 
 
350 INFECTIO US DISEASES. 
 
 Action of venous blood upon the temperature. A series of ex- 
 periments pursued by us demonstrated that the venous blood, unlike 
 the arterial, generally raises the temperature of the animals into 
 which it is injected. The hyperthermia is variable, since at times 
 it does not amount to more than a few tenths of a degree C, and 
 at other times it may attain 1° C. or more. 
 
 As venous blood generally possesses a thermogenic power which 
 is absent from arterial, the question rises whether this power depends 
 upon substances that are found in the extracts of tissues, or whether 
 it is due to bodies which appear in defibrinated blood, serum, or 
 urine. What modifications does the blood undergo by passing 
 through the lungs? Is it a transformation or an exhalation of 
 volatile thermogenic substances that occurs? Such are the ques- 
 tions to be asked at present, the solution of which requires untiring 
 experimental researches. 
 
 Since arterial blood differs from venous by the absence of a 
 thermogenic substance, it is rational to suppose that this substance 
 is eliminated by the lungs. This is, in fact, what takes place. The 
 water obtained by the condensation of the expired air when injected 
 in minute doses into the rabbit causes a more or less marked rise 
 in the temperature. 
 
 The hypothermizing power of arterial blood depends upon a sub- 
 stance antagonistic to that eliminated by the lungs; this substance 
 likewise exists in venous blood, but it is often masked by the thermo- 
 genic substance. 
 
 The hypothermizing substance proceeds from the tissues and is 
 eliminated by the kidneys. It is found in the urine, associated with 
 a new thermogenic substance. In fact, intravenous injections of 
 the urine produce an initial fall in the temperature, noted by Prof. 
 Bouchard, and give rise secondarily to a thermal elevation. Surely 
 we are in the presence of two antagonistic substances, for I have 
 succeeded in separating them. When the urine is treated with 
 alcohol the insoluble substances precipitated in the fluid lower the 
 temperature, while the soluble ones raise it. 
 
 It is readily conceivable that these substances, concerning the 
 chemical nature of which we have no data and which we know only 
 through their action upon the organism, may normally play a role 
 in the regulation of the temperature. Cold, by stimulating the 
 renal secretion, promotes the elimination of the hypothermizing 
 substance and hinders the exhalation of the volatile thermogenic 
 
GENERA L REACTIONS— FEVER. :>,:,] 
 
 element. The effect of heal is evidently the reverse of this; il 
 stimulates the elimination of the volatile thermogenic substance, 
 diminishes the secretion bythe kidneys, and binder* the elimination 
 of the hypothermizing element . 
 
 These data may explain certain pathological facte and notably 
 the hyperthermia produced by asphyxia and the thermal variation* 
 in cases of uremia. As we shall see, they elucidate a certain number 
 of features in the study of infectious fevers. 
 
 Role of the Liver, Kidneys, and Lungs in Thermogenesis. Feb- 
 rile movemenl may be profoundly modified by lesions or disorders 
 of certain organs. As yet the influence of the liver, kidneys, and 
 lungs only is known. 
 
 My attention was drawn to the r61e of the liver by observation of 
 two cases of typhoid fever at the end of ls(M). The Btrange course of 
 the temperature could be accounted for only by the far-reaching 
 alterations which the necropsy revealed in the liver. The distur- 
 bances were so pronounced, and modified the clinical course of events 
 to such a degree, that the author thought a hepatic type of typhoid 
 fever should be admitted. Setting aside the concomitant symptoms, 
 let us consider only the course of the temperature. The temperature, 
 lowered in both cases, returned to the normal, and fell even below 
 98.6° F. (37° C). Coincidently the general phenomena became aggra- 
 vated, and the patient succumbed at a time when, if the febrile 
 tracing only was taken into consideration, it would have been thought 
 that he was recovering. The autopsy revealed complete degenera- 
 tion of the liver, with a bloodless, yellow parenchyma. It was hyper- 
 trophied and weighed 1930 grams in one case. 2630 in the other 
 (normal weight being 1500 grams). Histological examination ami 
 chemical analysis showed that the gland had undergone acute fatty 
 degeneration; the amount of fat. which normally is about 2 per cent., 
 exceeded 9 per cent. 
 
 It seemed to me rational to connect the unusual course of the fever 
 with the hepatic alteration. In order to verify this supposition the 
 author undertook some experimental researches. The ideal would 
 evidently be to study the course of the temperature in animals whose 
 liver had been extirpated. Such mutilation, however, is not com- 
 patible with a survival sufficiently long to yield demonstrative 
 results. Some other method should therefore be employed. The 
 researches of Denys and Strubbe and those pursued by the author 
 with Dr. Gouget demonstrate that it is possible to destroy the hepatic 
 
352 
 
 ISFECTIO US DISEASES. 
 
 cells or. at least, the greater part of them, by injecting a dilute 
 solution of acetic acid into the biliary passages. 
 
 The operation is quite simple. A fine canula is introduced 
 through the duodenum into the ductus choledochus in such a manner 
 as not to disturb the course of the bile. The experiment lasts for 
 about half an hour, and the immobilization of the animal and the 
 reflex disturbances resulting from section of the abdomen lower the 
 temperature. 
 
 It was therefore necessary to previously study the hypothermia 
 induced by laparotomy. We learned that it generally oscillates 
 
 Fig. IS. 
 
 1 1 
 
 (Ol» 12 1 IS 
 
 21 
 
 80 
 
 3G 42 
 
 43 
 
 54 
 
 GO 
 
 GG 
 
 72 
 
 102.2° 
 
 100.4 C 
 
 98.G° 
 
 8D.8 C 
 
 95° 
 
 ~93.2 = 
 
 < 91.4° 
 
 | S9.6 C 
 
 t- 
 
 87.8" 
 
 86° 
 
 81.2" 
 
 S2.4" 
 
 80.6" 
 
 78.8' 
 
 , 
 
 | 
 
 
 
 
 
 
 \ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 y 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 \ 
 \ 
 
 
 
 
 
 
 
 
 
 
 
 
 \ 
 \ 
 
 
 
 
 
 
 
 
 
 
 
 
 \ 
 
 \ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 I 
 1 
 
 \ 
 
 : 
 
 ' 
 
 
 
 
 
 
 
 
 
 
 
 \ 
 \ 
 
 
 
 
 
 
 
 
 
 
 
 
 E: 
 
 cp.I 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 \ 
 
 
 
 
 
 
 
 
 
 
 
 
 ixp. 
 
 ill 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Ex] 
 
 Kill 
 
 Course of temperature in animals in which the liver was extirpated. 
 
 about 2.7° F. (1.5° C.) and lasts for a short time; as soon as the 
 animal is released the temperature again rises. If, on the contrary, 
 the hepatic gland is subjected to injury, the temperature, which at 
 times first rises, soon undergoes a new fall in a definite manner, after 
 having often presented slight and transitory rises. Thus, in a rabbit 
 in which 5 c.cm. of a 2 per cent, dilution of acetic acid had been 
 injected into the biliary passages, the temperature, which was pri- 
 marily at 102.4° F. (39.1° C), fell after the operation to 99° F. 
 
GENERAL REACTIONS FEVER 
 
 (37.4° C); it then rose and two hours later reached 101.1°] ■:- I I 
 but from that moment on it declined; seven houn later ii wa 
 97.9° F. (36.6° C), and at the end of fifteen hours, thirty minute* 
 before death, it had fallen to 87.8° F. (31° C). 
 
 In another rabbit submitted to the same experimenl the temp 
 I, urc followed a similar movemenl (Exp. I, Fig. L8). 
 
 When the animal survives longer the phenomena are more inter- 
 esting. Thus, in one rabbil (Exp. [I.) the temperature fell gradually 
 to S4.2° F. (29° C.) and, ;i lew minutes before death, to 81.5 I 
 (27.5° C). 
 
 In another instance (\')\\). III.) the animal survived seventy-two 
 hours, and the final temperature, a few minutes before death, 
 78.8° F. (26° C). 
 
 These absolutely concordant experiments prove that the destruc- 
 tion of the liver is followed by a progressive and very marked 
 lowering of the temperature. The phenomenon is quite difficult of 
 interpretation. Can the liver, according to the. experiments of CI. 
 Bernard, d'Arsonval, and Charrin, be considered as the main source of 
 organic heat? Can it be assumed that destruction of this gland, by 
 suppressing a focus of. heat, produces hypothermia in norma] sub- 
 jects and in infected subjects hinders the thermal rise which charac- 
 terizes fever? This conception might be maintained. It seems, how- 
 ever, more rational to assume that the action of the liver is an indirect 
 one. Suppression of the functions of this organ produces a modifi- 
 cation in general metabolism of the economy, a disturbance of the 
 nutritive exchanges which, under normal as well as under di- s 
 conditions, represent the true source of animal heat. 
 
 At all events, the explanation is of less importance than the fact. 
 The author's experiments, by demonstrating the existence of a hypo- 
 thermia of hepatic origin, seem to elucidate some clinical observa- 
 tions. They account for certain disturbances observed in the course 
 of infections affecting especially the liver, notably icterus gravis. 
 Apyrexia and hypothermia are not rare in certain forms of this 
 disease. Is this due, as Hanot asserted, to the nature of the infec- 
 tious agent concerned? AYe have experimental evidence that the 
 hypothermizing role of the colon bacillus has been exaggerated. Far 
 from lowering the temperature, this microbe often gives rise to fever. 
 The hypothermia of icterus gravis, therefore, seems to be due to 
 hepatic incompetency. It is true that, in certain cases, fever occurs 
 in spite of the hepatic degeneration, because hepatic insufficiency 
 
 23 
 
354 ISFECTIO US DISEASES. 
 
 does not suppress the production of heat any more than renal insuf- 
 ficiency does ; it only diminishes it. Moreover, the author has learned 
 by a series of experiments that the injection of microbic toxins into 
 animals the livers of which had previously been destroyed by inject- 
 ing a 2 per cent, dilution of acetic acid was followed by a thermal 
 elevation which caused the temperature to rise for a moment to its 
 initial height. 
 
 The kidneys very likely play a similar part. Incompetency of 
 these organs likewise induces hypothermia, as is evidenced by the 
 course of the temperature in uremic patients. It may, therefore, be 
 supposed that in a certain number of infections fever undergoes 
 oscillations referable to lesions of the kidneys. 
 
 On the other hand, pulmonary alterations represent an important 
 cause of hypothermia, Few diseases give rise to such high tempera- 
 tures as pneumonia. It may be alleged that the phenomenon is clue 
 to the action of the pneumococcus; it is, however, the same with 
 bronchopneumonia, regardless of the pathogenic agent, provided, of 
 course, that the sufferer is capable of reacting, for bronchopneumonia 
 in debilitated persons is at times attended by a low temperature 
 which is fairly explained by the general state. On the other hand, 
 that particular clinical form so frequent among children, and which 
 was once described as acute pulmonary congestion, is at present 
 looked upon as an abortive pneumonia and is often accompanied by 
 high fever. Experimentation, by demonstrating that the lungs elim- 
 inate thermogenic substances, explains perfectly their role in the 
 development of febrile movements. 
 
 Except the nervous system, the influence of other parts of the 
 organism is not as yet known. Since the nervous system plays an 
 important part in thermal regulation, it is readily conceivable that 
 according as the nervous centres are excited or paralyzed they may 
 increase or diminish the thermal degree. The intensity of fever in 
 children and its absence in the aged proves this assertion. 
 
 To sum up: the fever of infectious diseases is a reaction of the 
 organism against microbic toxins. With the same quantity of the 
 same toxin the febrile movement varies, on the one hand, according 
 to the localization of the process, and, on the other, according to the 
 state of the nervous system, and of the blood, and of certain organs, 
 such as the liver, kidneys, lungs, and, probably, the muscular system, 
 since we know that the principal chemical modifications calculated 
 to maintain the animal heat occur normally in the muscles. 
 
ENER . I L R /:. I ( "/'/ N8 FE I ' EB, 
 
 [f the author's conception is correct, fever mu I I"- con idered a 
 struggle against infection. The author speaks of fever, ool byper- 
 fchermia. 
 
 To return to his definition of fever, the author think?- that it i- 
 essentially characterized by an exaggeration of the chemical pro- 
 cesses occurring in the organism. Whether there be deviation from 
 tin* normal type or not, there is increase in the phenomena which 
 explain animal heat. In other words, there i- increased activil 
 nutrition. The organism, in order to combal the hypothermizing 
 action of toxins, stimulates combustion, and ae aoon ae a rise in 
 temperature occurs an exaggerated dissipation of beal follows. 
 This fact is interesting, since it is an example — we shall Bee many 
 others — of a modification which indicates the reappearance of a 
 functional state characteristic of a younger age. Ii ifl known 
 that nutrition as well as radiation of heal diminishes with the 
 advance of age; fever, then, is a return to a previous state of the 
 organism. 
 
 While fever is useful, hyperthermia may prove dangerous. In 
 combating it, preference should be given to those methods which 
 favor the dissipation of heat, while those that hinder nutritive activ- 
 ity should be avoided. Cold baths offer the best method, since 
 under their influence heat is readily dissipated at an increased rate, 
 and nutrition is at the same time stimulated. This method may. 
 therefore, be considered as a natural one; it is suggested by the pro- 
 cedure utilized by the organism itself. 
 
 It is not the elevation of temperature that is to be combated, but 
 an exaggerated elevation of it, since a moderate hyperthermia seems 
 to be favorable to the struggle against the microbes: it stimulates 
 the activity of the leucocytes, as was shown by Dr. Maurel, and it 
 increases the germicidal power of the blood, as has been demon- 
 strated by Kast, Henrijean, and Rovighi. 
 
 Thus, in spite of a few obscure points, we may at the present day 
 offer a rational conception of fever. In the study of the mechanism 
 presiding over its development we find valuable indications as to its 
 significance, its r61e in the defense of the organism, its usefulness and 
 dangers, and as to the means which, in certain cases, may be em- 
 ployed for restraining and combating it. 
 
 Characters of Fever in Some Infections. The application of 
 thermometry to clinical practice has made it possible to learn with 
 precision the characters of fever in various infections. Thus febrile 
 
35G 
 
 INFECTIOUS DISEASES. 
 
 processes have been divided into four classes, according as they are 
 continuous, remittent, intermittent, or irregular. 
 
 The continuous type is represented by cases in which the tempera- 
 t ure, at the stationary periods, remains at a determined height. The 
 classical example is typhoid fever. It is necessary to note, however, 
 that the temperature undergoes daily oscillations which are even 
 more pronounced than under normal conditions. It is known that 
 in health the temperature varies at different hours of the day. On 
 awakening, at 6 a.m., it is, on an average, at 98.5° F. (36.9° C); 
 it progressively rises for sixteen hours, and reaches its maximum, 
 which varies from 99.1° F. to 99.5° F. (37.3° C. to 37.5° C), toward 
 7 p.m. ; it then declines for eight hours, until 3 or 4 a.m., when it 
 falls to 98.2° F. (36.7° C), to rise again. It may, therefore, be stated 
 
 
 
 
 
 
 
 
 
 
 
 
 Fi 
 
 5. 19. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 99.68° 
 
 99.50° 
 
 ^ 99.32" 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 / 
 
 / 
 
 
 \ 
 
 \ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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 / 
 
 
 
 
 
 
 
 
 
 
 
 
 < 
 
 -it 08.50° 
 
 s 98.78° 
 
 H 98.60° 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 1 
 
 •i 
 
 3 
 
 
 5 
 
 G 
 
 ; 
 
 8 
 
 u 
 
 in 
 
 ii 
 
 12 
 
 l 
 
 i 
 
 3 
 
 4 
 
 S 
 
 G 
 
 7 
 
 8 
 
 'J 
 
 HI 
 
 11 
 
 12 
 
 i 
 
 HOUR (MORNING) (EVENING) 
 
 Daily course of the rectal temperature under normal conditions (after Jurgensen). 
 
 that, on an average, the normal variation of temperature amounts 
 to 1.4° F. (0.8° C). The same variations are encountered in disease, 
 but generally they are more marked. In typhoid fever the morning 
 temperature generally varies from 103.1° to 104° F. (39.5° to 40° C.) ; 
 that of the evening from 104° to 105.8° F. (40° to 41° C.) ; the dif- 
 ference is 0.9° to 2.7° F. (0.5° to 1.5° C). 
 
 The same is true of pneumonia and typhus, which are likewise 
 characterized at their stationary period by a so-called continuous 
 fever. The digressions are, however, no less clear than in typhoid 
 fever. It may, therefore, be stated that thermal variations in 
 diseases are generally nothing else than exaggeration of normal 
 phenomena. 
 
 When thermal remittences are considerable the temperature 
 returns at certain moments to the normal. The fever is then said 
 
QENEBA L REACTIONS FEVER, 
 
 
 to If intermittent [ntermittenl fever are often divided into two 
 groups: malarial intermittenl and symptomatic intermittent f< 
 
 The regularity of malarial intermil tence is well known. The ymp- 
 tomatic intermittent fevers differ from the malarial in thai thej 
 less regular. Unlike whal occurs in malaria, fever generally ap] 
 in the evening, sometimes recurs several I imes in one day, and reap- 
 pears at different hours on the following day. The paro hich 
 in most cases arc related io suppurating loci, are connected with 'lie 
 progressively increasing lesions: they are intermittent, while the evo- 
 lution of the lesions in continuous. They then resull probably from 
 a sudden reaction against ;i cumulative ad ion. Whatever the expla- 
 nation may be, febrile intermittence is only an exaggeration of 
 physiological remittences. 
 
 I i.;. 20. 
 
 
 1 
 
 M E 
 
 M E 
 
 3 
 
 M E 
 
 1 
 
 M E 
 
 .-> (1 
 
 M E 1 M E 
 
 7 1 Si 9 | 111 1 11 | IS | 18 1 14 
 ME[me[me'me'mE ME ME' me 
 
 is | in | 17 
 
 18 | 19 -Jii Jl CI 
 ME WE VE ME «E 
 
 
 
 
 
 
 
 
 
 
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 7 101 
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 r 
 < 
 
 ""l02.2 
 
 Q. 
 
 S 
 
 '-1(10.1 
 9S.G 
 
 
 
 
 
 
 
 
 
 
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 V \l \ 1 \ 1 \ 1 \ l\< 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 A 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 \ A 
 
 ■ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 W4 t 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 \/ \ A 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 V \ /\ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 / \ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 17 \ A A 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 w \ / \ / \ • 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 V \/ v/J 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 : 
 
 
 
 
 
 
 
 
 
 
 
 1 v Vi 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 i ' ■ hi 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 \/ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 1 -1 1 1 1 1 
 
 l 1 
 
 i 
 
 
 
 
 Schematic tracing of temperature of a typhoid case, according to Wunderlich. 
 
 In certain infections the course of the temperature is so regular 
 that its study aids diagnosis. Typhoid fever is the type of this kind. 
 Since the works of Wunderlich, the cyclic evolution of the tempera- 
 ture, with its progressive ascension, double summit, and descent by 
 lysis, is well known. (Fig. 20.) To this is contrasted the by no means 
 less typical evolution of pneumonic fever, with its abrupt onset, its 
 plateau, and its defervescence by crisis. The value of these characters 
 should not, however, be exaggerated. Often, especially during grave 
 epidemics, the course of fever in typhoid is absolutely atypical. In 
 order to be convinced of this it will suffice to bear in mind the course 
 of the temperature in the hepatic form of the disease. Even in cases 
 with a typical evolution, however, the course often deviates from the 
 schematic type. At times the onset, at other times the defervescence. 
 is abrupt; in other cases the stationary period is remarkable for 
 
358 IXFECTIO US DISEASES. 
 
 its oscillations, its sudden falls and unforeseen rises. On the other 
 hand, pneumonia may be attended by irregular fever and slow defer- 
 vescence. 
 
 Semiological Value of Thermal Course. As a result of the admir- 
 able contributions of Wunderlich it was believed that the deter- 
 mination of the thermal traces would be of great semiological value 
 and furnish important elements in diagnosis. As we have already 
 stated, a different conclusion is at present reached. Medical ther- 
 mometry serves for differentiating infections only in exceptional 
 instances. It serves rather to inform the physician of the evolution 
 of the process, the development, and at times the imminence of 
 complications, at the same time furnishing him with indications indis- 
 pensable for treatment. The unexpected rises or falls of the tem- 
 perature lead him immediately to look for the causes of these unusual 
 modifications. The changes of temperature may thus keep the 
 physician awake to the occurrence of various incidents, such as an 
 intestinal perforation, a hemorrhage, or even a secondary infection; 
 a decrease in fever has on several occasions been observed at a 
 moment when a second pyrogenic infection like pneumonia devel- 
 oped. 
 
 Likewise, after an apparent recovery from sjnnptoms, the ther- 
 mometer may inform us as to a relapse or some incident of convales- 
 cence. In other instances it indicates that the food given is too rich 
 or too abundant or that the slight exertion permitted is as yet too 
 fatiguing. Thus, while in the course of disease the thermometer in 
 a large measure guides the treatment, it directs hygienic surveillance 
 during convalescence. In both cases it furnishes valuable indications 
 which no other procedure can. 
 
CHA PTEB XIII. 
 
 INFLUENCE OF [NFECTIONS UPON VARIOUS PARTS 01 
 
 Til K ullC.WISM. 
 
 Modifications <>r the Blood in the Course "i Principal [nfections. Modification in the 
 Physical and Chemical Characters. Microscopic Study of the Blood. Varial 
 of the Leucocytes in i lie Principal Infections. Bacteriological Examination. Modi- 
 fications in the I lematopoiet ic Organs. 'I'lic Bone-maiTOW. i'nliniinar 
 of Normal Anatomy ami Physiology. Influence of Experimental [nfecl 
 Anatomical and Chemical Modifications. Eieaction of the Bone-marrow in 
 Semiology of the Hone-marrow. The Spleen in [nfections. Modifications in the 
 Lymphatic Glands. Variolar, Syphilitic, and Tubercular Adenopathies. Humoral 
 Modifications of Lymphatic Origin. The Thymus in [nfections. The Thyroid 
 Gland in Infections. The Suprarenal Capsules in infections. 
 
 Modifications of the Blood in the Course of Principal Infections. 
 
 The diffusion of toxins secreted by pathogenic agents and the inti- 
 mate solidarity uniting the different parts of the organism sufficient ly 
 explain the occurrence of more or less marked modifications in the 
 organs, tissues, and fluids under the influence of infections. T 
 modifications are of two orders: some represent true lesions; others, 
 simple functional changes. Of the latter, some express an increase 
 in activity; at times a return to a previous state — i. e., a kind of 
 rejuvenation of the organism. From this standpoint nothing is more 
 instructive than the study of the blood and of the hematopoietic 
 organs. 
 
 Examination of the blood in the course of infectious disei - - 
 enables us to watch certain changes occurring in the activity of the 
 organs or in the nutritional processes of the economy, and thus to 
 witness the various phases of the struggle engaged between the in- 
 vading organism and the invaded. Hematology has this important 
 advantage over pathological anatomy that it is practised upon the 
 living. Post-mortem examination of the viscera shows the results 
 of the defeat, but it does not explain its mechanism. By enabling 
 us to determine at each moment the conditions of the pathological 
 combat, the study of the blood furnishes us with diagnostic and prog- 
 
3G0 IXFECTIOUS DISEASES. 
 
 nostic data of importance', and may even suggest valuable thera- 
 peutic ideas. 
 Modifications in the Physical Characters. Ancient physicians, 
 
 who frequently resorted to bloodletting, were able to note the organo- 
 leptic characters of the blood in the course of infections, and they 
 have left us highly interesting information as to the mode of coagu- 
 lation and the appearance of clots. 
 
 The color of the blood is generally darker than under normal con- 
 ditions. This excessive venous character is mainly observed when 
 there is a disturbance in hematosis. Gubler and Renaut have noticed 
 however, that in grave typhoid conditions, malignant diphtheria, and 
 hemorrhagic types of eruptive fevers the blood presents a violet hue, 
 different from the dark color observed in asphyxia. They attribute 
 this state to an alteration in the hemoglobin. The same appearance 
 is evidently found at the necropsy. In cholera the blood is remark- 
 able for its thick consistence and dark color. That this is due to 
 some modification in the hemoglobin is demonstrated by the fact 
 that when shaken with oxygen the blood does not resume its red 
 color. 
 
 If infection has lasted for a long period and given rise to anemia, 
 the blood is pale and rose-colored. In some grave infections, par- 
 ticularly in nervous forms of typhus and typhoid fevers, it preserves 
 an abnormal arterialization in the veins; it is reddish in color. This 
 may be due to the excessive acceleration of the movements of the 
 heart which, at a given time, causes too much blood to pass into the 
 tissues, or it may depend upon insufficiency of organic exchanges, 
 owing to nervous derangement, and expressed in a diminished pro- 
 duction of carbonic acid. 
 
 The blood commonly preserves its habitual odor. In certain cases 
 of intense gastrointestinal disorders and putrid lesions, however, it 
 may be charged with nauseous gases. Morton reports that in a bad 
 case of fever the fetid character of the blood where it issued from the 
 vein was such as to almost cause the surgeon and his assistants to 
 faint. It is also said that the blood of variola and typhoid patients 
 exhales a fetid odor. 
 
 The modifications in the consistence of the blood played, as is 
 known, an important role in the pathogenic doctrines of Boerhaave. 
 It seems that the blood is simply thicker as a result of profuse loss 
 of fluids, markedly in cholera. The total mass is said to be then 
 diminished by one kilogram (quart). 
 
INFLUENCE OF INFECTIONS UPON THE ORGANISM. 36] 
 
 The mode of coagulation of the blood has attracted special atten- 
 tion. In some instances the clo! is firm, lightly retractile, and 
 crcd with a thick, fibrinous layer: this is the blood of phlegma 
 such as is observed in pneumonia, acute articular rheumatism, and 
 certain phlegmons, [n other cases the clot is soft, tending to di 
 in the scrim i : such is the blood in grave fever-, i yphua fever, bubonic 
 plague, and typhoid fever. 
 
 In plain phlegmasias, notably in pneumonia, the blood coagulates 
 more slowly than under normal conditions. The clol is remarkably 
 small, concentrated, and firm; the deeper layers are red: the outer 
 surface is formed of a yellowish-white layer which is firm and thick. 
 This appearance of the clol is due to the excess of fibrin, the amounl 
 of which may rise from 2.5 to 10 per 1000. As is known, fibrin plays 
 an important role 1 in the defense of the organism againsl the pneu- 
 moeoccus, and it is therefore possible to draw some valuable deduc- 
 tions with reference to prognosis. The upper layer is thicker in pro- 
 portion as the individual is more robusl and the inflammation more 
 intense. According to Hourmann and Dechambre, the blood in the 
 aged is seldom covered by the usual upper layer, a fact well in har- 
 mony with the lack of defensive reactions at this age. Louis and 
 Grisolle have noted that, the upper layer is often absent in fatal cases 
 and seldom lacking in favorable cases of pneumonia. Among the 
 former it is wanting in one-fifth of the cases; among the latter in 
 only one out of eleven instances. 1 
 
 In grave pyrexias, hemorrhagic types of eruptive fevers, typhus 
 fever, bubonic plague, diphtheria, and pneumonia of typhoid form 
 the blood coagulates slowly and incompletely. The clot is soft, 
 non-retractile. The upper surface is plain, not concave, and covered 
 by a slight layer of fibrin. The serum is scanty and the clot has a 
 tendency to dissolve in the serum. 
 
 The mechanism of these phenomena has been a subject of dis- 
 cussion. Some authorities have attributed them to modification 
 in the amount of fibrin, and others to a change in coagulability of 
 the latter. However this may be, the amount of fibrin which 
 coagulates varies markedly with the group of infections considered. 
 The following figures, borrowed from the highly interesting investiga- 
 tions of Andral and Gavarret. give a clear idea in this respect. 
 These authors take the normal proportion of fibrin to be 3: 1000. 
 
 1 Grisolle. Traite tie la pneumonie. Second edition. 1S64. p. 257. 
 
3G2 INFECTIOUS DISEASES. 
 
 X umber X umber of Average 
 
 Disease. of Cases. Venesection, of Fibrin. Maximum. Minimum. 
 
 Pneumonia 20 57 7.47 10.5 4.0 
 
 Acute articular rheumatism . 14 41 6.S9 10.2 4.1 
 
 Acute peritonitis .... 4 6 6.2 7.2 4.7 
 
 Erysipelas 5 S 5.67 7.3 6.2 
 
 Scarlatina 2 2 3.3 3.5 3.1 
 
 Variola 5 12 2.92 4.4 1.1 
 
 Measles 7 9 2.S 3.6 2.4 
 
 Typhoid fever 19 43 2.52 3.8 0.9 
 
 Spectroscopic examination of the blood may also be of great 
 service for the study of its physical properties, as has been shown 
 by Henocque. The investigations of Henocque and Beaudoin prove 
 that, in typhoid fever, the energy of consumption of the oxygen 
 of the blood by the tissues is in inverse ratio to the elevation of 
 temperature. Fever diminishes the activity of oxidations and 
 exchanges. 
 
 Chemical Modifications. The chemical modifications suffered by 
 the blood in the course of infections are extremely profound, as is 
 evidenced by the modifications in the biological properties of this 
 fluid. They are so delicate, however, and bear upon such unstable 
 substances that an exact analysis is a matter of great difficulty. In 
 fact, no well-marked changes are discovered when the usual pro- 
 cedures are employed. 
 
 The reaction remains alkaline. In some cases of cholera it has 
 been found to be neutral or slightly acid. The amount of water 
 varies inversely to the globular richness and increases progressively 
 under the influence of repeated bloodletting. As to the amount of 
 fibrin, pneumonia exerts the most marked influence, since in this 
 disease it reaches the proportion of 7.47 per 1000 on an average, 
 10.5 being the maximum. Even when this disease occurs in indi- 
 viduals already suffering from an affection which diminishes the 
 amount of fibrin, such as purpura and cancer, pneumonia gives rise 
 to an increase of this substance. It is said that albumin is dimin- 
 ished when fibrin increases. According to Becquerel and Rodier, 
 the addition of these two substances gives the normal total weight. 
 
 It would be interesting to study the products of disassimilation, 
 notably urea, ammonia, and extractive matters. Urea is increased 
 in the blood mainly when the renal secretion is profoundly disturbed, 
 as is the case in cholera and variola. In cholera as much as 3.6 per 
 1000 of urea may be found. On the other hand, when the liver is 
 altered the extractive matters accumulate in the blood. 
 
INFLUENCE OF INFECTIONS UPON THE ORGANISM. 303 
 
 The variations in the amounl of glucose tnusl tiol be overlooked. 
 I have pursued on this subject some experiment! upon animals 
 inoculated with anthrax. In operating upon cadavers I thus noticed 
 that the blood contained no glucose. In view, however, of the 
 rapidity with which sugar disappears after death, the experimenl 
 was not conclusive. II blood is taken a1 the tnomenl when the 
 animal succumbs ;in r\f icincly intense reduction "I Pehling' jolu- 
 tion is obtained. During I he firsl stage of anthrax, while the general 
 state of the animal is apparently excellent, the blood contains 0.7] 1 
 to 1 gram of sugar per 1000. This proportion i- somewhal below 
 thai round in well-nourished normal rabbits, in which it varies from 
 1.25 to 1.40 grams per 1000. 
 
 During the second stage, when the anthrax bacilli pass into the 
 blood and the temperature of the animal is lowered, sugar incri 
 in notable proportions — it reaches the proportion of 2.24 and even 
 2.976 grams per 1000. This is probably due to diminished con- 
 sumption of sugar, as seems to be evidenced by the fall in temper- 
 ature — another proof of the decrease in nutrition activity. 
 
 The chemical modifications of the blood explain the modifications 
 of its biological properties, viz., of its action upon the figurate 
 elements. Thus, the globulicidal power increases in pneumonia, 
 typhoid fever, erysipelas, and tuberculosis. In certain experimental 
 infections the serum becomes more germicidal than normal, even 
 when the disease terminates fatally. These questions will again 
 be referred to. 
 
 In recent investigations Achard and Gere endeavored to show 
 the pathological variations produced in the ferments of the blood 
 serum. These authors proved that considerable attenuation of 
 lipase and amylase is a serious symptom and often indicates approach- 
 ing death. This result is equally true with regard to cachectic 
 conditions and acute or chronic infections, such as pneumonia, 
 typhoid fever, and tuberculosis. Experimental researches pursued 
 in our laboratory by Dr. Clerc demonstrated the development of 
 similar modifications in inoculated animals. These ferments are 
 the evidences of the activity of the organism. Their study may. 
 therefore, be useful for diagnostic purposes. 
 
 Microscopic Study of the Blood. Microscopic examination of the 
 blood shows not only the number and characters of the corpuscles, 
 but also reveals the mode of coagulation of the fibrin and. in some 
 measure, its quantity. Hayem has given a perfect description of 
 
364 1XEE( Tin I -s J) I SEA SES. 
 
 the mode of coagulation of the blood in phlegmasia^, such as pneu- 
 monia, and rheumatism. Coagulation is slightly retarded. This 
 modification coincides with an increase of the leucocytes and the 
 presence of phlegmasic masses formed of "hematoblasts" which a 
 viscous substance unites with red and white blood corpuscles. 
 
 In the majority of infections the number of red blood corpuscles 
 and "hematoblasts" is diminished, and this diminution becomes 
 more and more pronounced the longer the disease continues. The 
 red globules are often altered; they contain less hemoglobin than 
 under normal conditions. Hence they are lighter in color, and 
 some appear completely destitute of pigment. This occurs in cases 
 of adynamic typhoid fever, hemorrhagic variola, and typhopneu- 
 monia. 
 
 These modifications in the red corpuscles explain in part the dis- 
 turbance occurring in the respiratory exchanges and, secondarily, 
 in general nutrition. In most cases it is quickly repaired. In 
 certain predisposed individuals, however, reparation is incomplete, 
 and infection is followed by a more or less persistent anemia, at 
 times even by chlorosis. This occurs in consequence of the most 
 varied acute diseases as well as in the course of certain chronic 
 maladies, such as tuberculosis, malaria, and syphilis. 
 
 Variations of the Leucocytes. Since attention was drawn to the 
 considerable role played by the leucocytes in the protection of the 
 organism, great interest has been aroused in the study of the modi- 
 fications which these cells may undergo. An endeavor was first 
 made to determine their numerical variations. It has recently 
 been recognized, however, that this study is insufficient; the quali- 
 tative modifications must be taken into account; that is, the changes 
 occurring in the different varieties of leucocytes must be determined. 
 
 It may be broadly stated that in the majority of infections 
 hyperleucocytosis is produced, which is the more marked the more 
 resistant the individual. Under the influence of the same amount of 
 a given virus a vaccinated animal presents a more intense leuco- 
 cytosis than an animal without such experience. This result is 
 readily conceivable in view of the protective role of the white 
 blood corpuscles. In fatal cases the number of the leucocytes 
 diminishes as the morbid symptoms become aggravated. 
 
 The number of leucocytes per cubic millimetre being normally 
 from 6000 to 8000, leucocytosis is said to exist when 10,000 are 
 counted. This figure is often exceeded, but it hardly ever rises 
 
INFLUENCE OF INFECTIONS UPON THE ORG iNl H 
 
 above 30,000, and bu1 exceptionally reache 60,000 or 115,000 
 was the case in a pneumonia reported by Loehr. Among infections 
 which most frequently give rise to leucocyte i '■ may '-it'- pneu- 
 monia, suppurations of all kinds, gonorrhea, and glander . On the 
 oilier hand, typhoid fever and measles cause bul a 3ligh1 and transi- 
 tory increase of the leucocytes. Scarlatina U attended by a leuco- 
 cytosis which persists long after the fall of temperature. In tetanus 
 leucocytosis varies from 15,000 to 20,000. In tuberculosis the 
 figures are from 10,000 to 20, 000. When, however, m caseoUE focus 
 breaks down and purulenl expectoration supervenes the Dumber 
 of leucocytes at times reaches 36,000 (Hayem). 
 
 It may broadly be stated thai leucocytosis begins, progresses, and 
 declines with the disease. 
 
 As to the qualitative modifications of the leucocytes, it must first 
 be noted that it is mainly the neutrophilic polynuclears which are 
 increased. In gonorrhea the eosinophils are said to increase; in 
 whooping-cough the lymphocytes; in variola and varicella the 
 mononuclears. 
 
 It is important to determine for each infection the numerical 
 variations undergone by each variety of leucocytes. 1 This has been 
 done by Chantemesse and Rev for erysipelas. In adults who recover, 
 the polynuclears suffer a diminution until recovery is confirmed. 
 The large mononuclears, the number of which does not vary much 
 during the febrile period, increase considerably immediately before 
 or at the beginning of defervescence. The variations of the lympho- 
 cytes follow a reverse course, and their increase is a certain sign of 
 a positive cure. The eosinophils, commonly absent during the 
 febrile period, reappear at the moment of defervescence. In fatal 
 cases hyperleucocytosis always exceeds 12.000 and is characterized 
 by a polynucleosis which reaches or exceeds the proportion of 92 per 
 cent. The persistence or sudden return of polynucleosis in the 
 course of convalescence indicates the imminence of a relapse. Thus, 
 the interest of this study for diagnostic purposes is considerable. 
 
 The same study with regard to typhoid fever has been made by 
 Chantemesse, Millet, and Stienon. At the beginning the absolute 
 number of the leucocytes is diminished. The polynuclears. however, 
 are more numerous than normal. They constitute 70 or even 90 
 per cent, of the total number. The lymphocytes are diminished. 
 
 1 Consult the general review by Josue. " Fonnule hemoleucocytaire de quelques mala- 
 dies infeetieuses." Gazette des hopitaux. December 15, 1900. 
 
366 INFECTIOUS DISEASES. 
 
 while the eosinophiles are almost entirely absent. In the second 
 stage the number of leucocytes is always below the normal; the 
 number of the mononuclears, however, and particularly of the 
 Lymphocytes, rises, while that of the polynuclears diminishes by 
 sudden falls. During convalescence the polynuclears are not very 
 numerous, while the lymphocytes increase, and the large mono- 
 nuclears represent 20 to 30 per cent, of the total figure. The increase 
 in the number of the eosinophiles announces that convalescence will 
 supervene within a day or two. The return to the normal is subse- 
 quently effected in a slow or progressive manner. Should some 
 inflammatory complication occur it is announced by a sudden 
 increase in the polynuclears. 
 
 In this connection typhoid fever may be contrasted with 
 pneumonia, which, unlike the former, is a disease characterized by 
 an abrupt development. Numerous hematological investigations 
 demonstrate that the number of leucocytes rises suddenly after the 
 initial chills. The polynuclears predominate ; before the crisis they 
 reach 80 per cent.; on the eve of crisis they rise to 86 per cent., to 
 fall to 71 per cent, after defervescence and to 57 per cent, on the clays 
 following (Leredde). At this moment an increase in lymphocytes 
 and eosinophiles is observed, the latter rising from 3 per cent, to 
 5, to 6, or even 7 per cent. (Turck). In cases in which polynucleosis 
 persists after defervescence the termination of the disease should be 
 considered incomplete. If the polynuclears increase, suppuration of 
 the exudate is to be feared. 
 
 The infections characterized by mononucleosis constitute a very 
 particular group. Aside from whooping-cough (Mennier) the patho- 
 genic agent of which is unknown, we see that all of them are pro- 
 duced by protozoa. This has first been demonstrated with regard 
 to malaria. During a paroxysm there is first an increase of lympho- 
 cytes and, in a less degree, of eosinophiles and large mononuclears. 
 Fifteen to twenty minutes later the lymphocytes are more numerous 
 and the large mononuclears rarer. The polynuclears undergo scarcely 
 any change. 
 
 The author believes variola to be due to a protozoon of a quite 
 different order. Whether this parasite develops in man or is inocu- 
 lated into rabbits it gives rise to mononucleosis. Leucocytosis may 
 be moderate. In a total of 36 cases, studied in our wards, we found 
 19 -times 6000 to 15,000 leucocytes per cubic millimetre, 12 times 
 15,000 to 20,000, 3 times 25,000, and in the last two cases 30,000 to 
 
INFLUENCE f)E INFECTIONS UPON THE ORGANISM, 
 
 .'i5, ooo. Although leucocytosis is present from the beginning, it i- 
 particularly intense at fche time of vesiculation, and remain 
 tionary, slightly diminishes, or increa e during pu tulation. In the 
 hemorrhagic Tonus it is less marked, bul i- 3eldom ab ent. 
 
 In scarlatina the number of the leucocytes is, according to Kolshet- 
 kofT, from 10,000 to 20,000 in lighl cases, 20,000 to 30,000 in i 
 of ordinary intensity, more than 30,000 in grave cases. The poly- 
 nuclears represent sf> to os per cent.; the eosinophiles, which are 
 
 slightly decreased at, the beginning of (he disease, grow more and 
 more numerous during its course: they diminish and may even 
 disappear in grave eases. 
 
 Bacterioscopic Examination of the Blood. Microscopic examina- 
 tion of small drops of blood al times reveals the presence of patho- 
 genic agents, and thus gives valuable clinical information. Such is 
 particularly the case in malaria — the presence of the peculiar hemato- 
 zoon enables us to reach a positive diagnosis. In hemorrhagic 
 variola, as well as in congenital smallpox, the blood contains 
 corpuscles characteristic of this infection. The same elements are 
 found in the blood of inoculated animals, at least when the disease 
 evolves rapidly. 
 
 When practised during a paroxysm of recurrent fever, examination 
 of the blood reveals the presence of the spirilla of Obermeier. The 
 parasite cannot be seen during the intervals of the paroxysms. 
 
 The microscope more rarely permits the detection of bacteria. 
 The latter are hardly ever seen except toward the end of disease 3. 
 Such particularly is the case in anthrax — the presence of the anthrax 
 bacilli in the blood indicates a general infection and announces the 
 approach of a fatal termination. 
 
 This does not mean that bacteria do not invade the blood, even 
 in cases of curable infections, but that the germs are always present 
 in such small numbers that it is difficult to detect them by a simple 
 microscopic examination. To obtain precise information, cultiva- 
 tion and, sometimes with advantage, inoculation must be resorted 
 to. By employment of these various procedures the tubercle bacillus 
 has been detected in the blood in cases of acute miliary tuberculosis 
 (Weichselbaum) and. more rarely, the bacillus of glanders and that 
 of typhoid fever. The latter, which is only very exceptionally 
 encountered in the blood of the general circulation, is often met 
 with in the rose-colored spots of the skin and. almost constantly, in 
 the blood of the spleen. 
 
368 INFECTIOUS DISEASES. 
 
 The microbes of septicemia — the staphylococcus, streptococcus, 
 and pneumococcus — invade the blood oftener than is generally 
 believed, but they are present in such small numbers that it is 
 difficult to detect them. When, however, a considerable amount of 
 the blood is cultivated or inoculated it is seen that the microbes 
 are present in the blood even in benign cases, although they art 1 
 more numerous in grave cases. In this respect the figures given by 
 Beco are altogether conclusive. Of fifty-six patients suffering from 
 pneumonia eleven had the pneumococcus in the blood. Of twenty- 
 nine of these patients who recovered, in only two was the blood 
 invaded. Among the twenty-seven who died the blood was infected 
 in ninety. 
 
 It is well to add that the staphylococcus has also been found in 
 the blood in cases of furunculosis, anthrax, osteomyelitis, and puer- 
 peral or surgical infections. According to Sittmann, its presence does 
 not render the prognosis so serious as does that of the streptococcus 
 or pneumococcus. 
 
 Modifications of the Hematopoietic Organs. Of the numerous 
 modifications suffered by the blood in the course of infectious dis- 
 eases some are, perhaps, due to the direct action of microbic toxins, 
 but most of them depend upon previous modifications of the organs 
 or tissues. The blood being a production of cellular origin, its 
 changes indicate previous modifications in the organs concerned in 
 the task of assuring its chemical constitution or furnishing it with 
 figurate elements. It is, therefore, natural to investigate the occur- 
 rences in the hematopoietic organs. For consideration of the mor- 
 phological elements attention must be drawn to the organs in which 
 the red and the white blood corpuscles are formed — the bone-marrow, 
 spleen, lymphatic glands, and the thymus. 
 
 As a result of the admirable researches of Ehrlich it was believed 
 that the hematopoietic organs could be divided into two groups. 
 One group is constituted by the lymphoid tissue and gives rise to 
 non-granular mononuclears, namely, the lymphatic glands, the 
 spleen, and the lymphoid structures of the digestive tract. The 
 other group, represented by the myeloid tissue, is said to be the 
 source of red blood corpuscles and granular polynuclear leucocytes. 
 So sharp a distinction is no longer admissible. The researches pur- 
 sued by me with Dr. Josue showed that view to be too sweeping as 
 regards the bone-marrow. The histological examinations which I 
 made with Weil tend to prove that the study of variola does not 
 
INFLUENCE OF INFECTIONS UPON THE ORGANISM. 
 
 confirm this dichotomy, Finally, in s highly remarkable eri 
 researches, Dominici systematically studied the various hemato- 
 poietic organs of man and animals and demon trated thai the spleen 
 may undergo a total myeloid transformation, as notably occui 
 ;i resull of repeated hemorrhages. He further demonstrated thai 
 vaccine virus causes the appearance of basophilic and amphophilic 
 myelocytes and nucleated red blood corpuscles in the lymphatic 
 glands. 3 It may, therefore, be concluded thai the various lymphatic 
 cells may originate in all the organs concerned in hematopoiesis. 
 If, under normal conditions, each organ contains exclusively one sorl 
 of leucocytes, infection c.'iuses these seemingly fixed distinctions to 
 disappear. Thus, cellular types, which were no longerfound in the 
 adult, reappear, indicating ;i return to conditions <>f fetal life. 
 
 The Bone-marrow in Infections. 
 
 Preliminary Considerations of Normal Anatomy and Physiology. 
 The bone-marrow has long been considered a tissue filling up the 
 interior of bones to give them solidity without increasing their 
 weight. It is now known that it discharges in the economy numerous 
 functions of importance. This new conception has been accepted 
 with some difficulty. In fact, the cellular elements, which evidently 
 represent the active part, diminish and disappear as the individual 
 grows; fat takes their place, so that the marrow seems to lose all it- 
 functional importance. It comes to a state of rest. As soon, 
 however, as a new physiological or pathological condition requiring 
 the production of white or red blood corpuscles supervenes, the fat 
 is absorbed, the cells proliferate, and in some instances finally 
 become as numerous as in young subjects. Instead of the yellow 
 color which the marrow presents in the adult, it becomes red. as in 
 the beginning of life; it resumes the fetal character. Thus, histo- 
 logical examination may inform us as to the degree of activity of 
 the bone-marrow. 
 
 It is known that the bone-marrow seems to be formed of fatty 
 tissue in the adult. A more attentive study shows, however, that 
 it is a tissue of well-determined texture. It contains two serii - 
 cellular forms; some are destined for the production of leucocytes, 
 the other for the production of cells with hemoglobin. 
 
 1 Dominici. Sur le plan de structure du systeme hematopoietique do? maim 
 Archives de med. exper.. July. 1901. 
 
 24 
 
370 IXFECTIOUS DISEASES. 
 
 The cells of the first series — i. e., the myelocytes, generally measure 
 from 14ft to 20/*. have the appearance of mononuclear leucocytes, 
 but differ from them by the presence of protoplasmic granulations 
 similar to those found in the polynuclear leucocytes of the blood. 
 According to their tinctorial properties the granulations are divided 
 into oxyphiles or eosinophils, pseudoeosinophiles, neutrophiles, and 
 basophiles. The neutrophil myelocytes are the most profusely 
 distributed. 
 
 The bone-marrow likewise produces red blood corpuscles. It is 
 possible to follow the various stages of the evolution of the nucleated 
 red globules. 
 
 The bone-marrow seems also to be capable of producing, especially 
 under pathological conditions, soluble substances; as the latter 
 always proceed from cellular secretions, the proliferation observed 
 in the course of diseases is favorable to this conception. 
 
 It is hardly necessary to recall the role played by the bone-marrow 
 in the nutrition and regeneration of bones. 1 Finally, the marrow 
 is capable of absorbing as well as of secreting. The experiments of 
 Dubuisson-Christot demonstrated that substances introduced into 
 the medullary canal of long bones rapidly pass into the general 
 circulation, even more rapidly than when injection is made into the 
 peritoneum or the liver. 
 
 Modifications of the Bone-marrow in Experimental Infections. 
 The bone-marrow becomes the centre of defense for the organism in 
 a number of infections and intoxications. This role, which we 
 endeavored to elucidate in a series of researches published with 
 Dr. Josue, had but rarely been studied before us. In December, 
 1896, we reported our first investigations on the state of the bone- 
 marrow in suppurations, pointing out the important modifications 
 in the structure and texture of this tissue. 2 Dominici, 3 proving 
 the appearance of nucleated red globules in the blood of infected 
 
 1 Oilier. De la moelle cles os et de son role dans 1 'ossification. Journal de la phys- 
 iologic 1863. Goujon. Recherches expeximentales sur les propri£t£s physiologiques de 
 la moelle. Journal d'anatomie et de physiologie, 1869. 
 
 2 Roger and Josue\ Recherches experimentales sur les modifications de la moelle 
 osseuse dans les suppurations. Soc. de biol., Dec. 12, 1896, p. 1038. Action de la toxine 
 et de l'antitoxine diphteriques sur la moelle osseuse, ibid., Jan. 9, 1897. Des modifi- 
 cations histologiques et ehimiques de la moelle osseuse aux differents ages et dans 
 l'infection staphylococeique, ibid., March 25, 1899. Des modifications histologique 
 ehimiques de la moelle osseuse dans l'inanition, ibid., May 5, 1900. 
 
 3 Dominici. Tumeur de l'ampoule de Vater. Soc. anat., 1S96, p. 708. Septicemic 
 exp. a globules rouges nucleus, ibid., 1896, p. 714. 
 
INFLUENCE OF INFECTIONS UPOH THE ORGANISM, ;;71 
 
 rabbits, attributed this phenomenon to the reaction oi the bone- 
 marrow. About the same time Trambu ti tudied tli*' bone-marrow 
 of guinea-pigs in diphtheria and laid Jtre on the igne of functional 
 activity which this disease imposed upon the cellg of the marrow. 
 
 The reaction of the bone-marrow is expre* ed not only by cellular 
 modifications indicating increased activity,bu1 also by topographic 
 changes easily noticeable on sections, even when examined by the 
 unassisted eye. The marrow gives rise to blood cells endowed with 
 phagocytic properties ; consequently, when an increased numbei ol 
 these is required, the original cells or myelocytes, intermediate 
 forms, even the polynuclears, are likewise increased in the medullary 
 tissue. The latter is thus invaded by a tremendous number of cells. 
 
 By giving birth to the leucocytes, which will pick up, digest, and 
 destroy pathogenic germs, the bone-marrow plays a rdle of prime 
 importance in the defense of the organism; it supplies it with the 
 army which will defeat the invaders. It is, therefore, a1 the momenl 
 of clanger that this tissue 1 displays the greatest energy. 
 
 The role of the bone-marrow thus seems to be more complex. 
 Although there is no direct demonstration, it is highly probable that 
 the marrow possesses secretory and antitoxic properties. This is 
 indicated by the multiplication of medullary cells in the course 
 of various intoxications and consecutively to the introduction of 
 certain sera. 
 
 This reaction of the bone-marrow is observed in a great number 
 of conditions. Staphylococcic infection, which was the first subject 
 of our investigations, may be cited as an example. 
 
 Modifications in the Bone-marrow in Experimental Staphylococcic In- 
 fection. In these experiments we employed adult rabbits weighing 
 from 2000 to 3200 grams. We chose such heavy animals in order to 
 be certain that their marrow presented the adipose type. In fact, 
 it is known that the cellular elements, which are very abundant in 
 the young, diminish with age and, in the adult, are replaced by fat. 
 
 If a culture of medium virulence be employed the modifications 
 which result from a subcutaneous injection may easily be watched 
 in the bone-marrow. Forty-eight hours after the injection of 1 c.c. 
 of the culture, the local lesion — i. e., suppuration — appears. At this 
 moment leucocytosis is at its maximum: the leucocytes are found 
 to number from 12,000 or 15.000 to 30.000 or 40.000 per c.mm. If 
 the animal is killed the bone-marrow presents a red color, con- 
 siderable congestion, and multitudes of red cells. The medullary 
 
372 
 
 IXFECTIO US DISEASES. 
 
 cells are also increased and particularly profuse in the peripheral 
 parts. 
 
 The modifications progress so that, on the fifth day, the marrow 
 is constituted simply of cells mixed with red corpuscles and accumu- 
 
 Fig. 21. 
 
 Bone-marrow of a normal rabbit. On the left side, the sinus with its artery; on the 
 right, the cortical layer. At the centre, the areolar tissue containing a small number 
 of cells. 
 
 Fig. 22. 
 
 Bone-marrow of the rabbit in neutrophilic reaction. Considerable increase in the 
 number of cells; diminution in volume of fatty areolre. 
 
 fated in large numbers at certain points. There is nothing left of 
 the normal arrangement, no more areolae full of fat. 
 
INFLUENCE OF INFECTIONS UPON THE ORGANISM. ;;7.; 
 
 At the end of fifteen days rel rogre ion of the proce i observable; 
 the normal conditions tend to reappear here and there) areolae full 
 of fat are again found, remarkable only for their smaller dimension , 
 
 To sum up, all the cellular elements Lncrea e in number and \/< 
 they are in a state of intense activity. The inerl elements, which, 
 under normal conditions or rather in a state of rest, form the gre 
 part" of the tissue, give way to the active elements. 
 
 A question may be raised here: May one variety of celU multiply 
 in :i predominanl or exclusive manner? In other words, are there 
 neutrophilic, eosinophilic, or normoblastic reactions? 
 
 In the lii'si place, it is to be recognized thai there is never an 
 absolutely exclusive multiplication of cells. In the cases which we 
 examined a certain degree of irritation and proliferation of other 
 species existed. Likewise, in the neutrophilic reaction of suppura- 
 tions and certain infections there is multiplication of other varieties 
 of cells. 
 
 I i.;. 23. 
 
 Bone-marrow of normal man. Sinus containing an artery. Few cells. Fatty areoUe 
 
 of large size. 
 
 Reactions of the Bone-marrow in Man. The human bone- 
 marrow seems to lose most of its activity at an early age. When, 
 however, an intoxication occurs it again assumes the type observed 
 in childhood : it resumes its functions in order to protect the organism. 
 The cellular elements, which were extremely rare when the organs 
 were not engaged in struggle, become very numerous. The reac- 
 
374 
 
 IXFECTIO US DISEASES. 
 
 tion, however, is less readily produced and less marked than in the 
 rabbit. 
 
 Let us take, for example, the neutrophilic reaction of the bone- 
 marrow in tuberculosis. 1 The proliferated bone-marrow is darker 
 in color, softer, and at times pasty. Under the microscope it is seen 
 that cellular proliferation is not at once progressing throughout the 
 entire thickness of the marrow. The invasion by the cells is at first 
 partial; their distribution is not clearly systematic. Even in the 
 midst of proliferated parts there may be found fatty areolae, though 
 not so large as normal. 
 
 Fig. 2-4. 
 
 
 
 
 dj 
 
 
 
 
 Human bone-marrow in neutrophilic reaction. Enormous increase in the number of 
 cells ; the areola? are far less numerous and voluminous than normally. (Compare with 
 Fig. 23.) 
 
 When considerably magnified all the cells are found to be in- 
 creased in number, although the neutrophile myelocytes are pre- 
 dominant, mixed with all the intermediate series ending in poly- 
 nuclears. The giant cells are not as large as in the rabbit. In the 
 midst of all these elements are observed masses of pigment colored 
 black by ammonium sulphydrate. 
 
 The Bone-marrow in Smallpox. The recent epidemic of variola 
 in France offered an opportunity to take up this study and, by means 
 of numerous improvements in fixation and staining, to complete and 
 
 1 Josue. Moelle osseuse des tuberculeux et histogenfese du tubercule. These de Paris, 
 1898. 
 
TNFLUKNdK or ISFMJTI0XT8 UPON THE ORG I I v. 375 
 
 modify in some respects the result alr< ady obtained. The re 1 archee 
 of Dr. Courmonl and Montagard 1 pursued coincidently with 1 
 and published only three weeks after our firsl note, 2 confirm the 
 principal facts se1 fori h by us. 
 
 In two cases of variola we noticed an absence of medullary reaction. 
 This is an exception. Ai all events, however, the reaction of the 
 bone-marrow manifests little intensity, ai leasl in the adult. Our 
 
 Fig 25, 
 
 Section of bone-marrow in variola. Moderate proliferation of cells 
 
 surrounding the vessels. 
 
 confined to the area 
 
 observations on this point are at variance with those of Golgi. 3 who 
 laid stress upon the intensity of the reactionary phenomena which 
 the bone-marrow presented in the cases studied by him. However, 
 by comparing the results furnished by a topographic examination 
 of the marrow with those obtained by counting The white corpuscles 
 
 1 Courmont and Montagard. La moelle osseuse dans la variole. XlTle Cong - 
 international de medecine. Section de path, generate. Paris. August. 1900. p. L87 
 
 2 Roger, Josue. and Emile Weil. La moelle osseuse dans la variole. Soe. anat. 
 July 13, 1900. Archives de rued. exp.. September. 1900. 
 
 3 Golgi. Sulle alterazioni del midollo del ossa nel vainolo. Rivista elinica di Bologna, 
 1873, p. 238. 
 
376 IXFECTIO US DISEA SES. 
 
 on the eve of death we find an absolute concordance. Though the 
 proliferation of the cells is poorly marked or nil in the medullary 
 tissue, the number of leucocytes contained in the blood itself is not 
 great, varying from 6000 to S000, not exceeding 442S in cases of 
 confluent variola with terminal hemorrhages in which the bone- 
 marrow was fatty. 
 
 The appearance of the bone-marrow in children suffering from 
 variola is altogether different. The latter were all attacked by 
 bronchopulmonary infectious complications. The marrow was red 
 and invaded by large numbers of cells. The fatty areolae had com- 
 pletely disappeared. The cellular formula in smallpox may be 
 briefly laid down as follows: marked predominance of the mono- 
 nuclears, relative diminution of the polynuclears. This is in accord 
 with the findings of a qualitative examination of the blood, in which 
 the polynuclears are likewise present in small numbers, while the 
 mononuclears are more abundant than normally, and belong in part 
 to different varieties which are not found under normal conditions: 
 myelocytes, forms of irritation of Tiirck, etc. 
 
 The reactionary manifestations are the same in both pustular and 
 hemorrhagic variola. 
 
 Lesions of the Bone-marrow in Infections. Apart from those 
 modifications which occupy the undecided boundary between 
 healthy and diseased conditions, since they indicate a struggle 
 against a pathogenic agent, true lesions may also be observed in the 
 medullary tissue. 
 
 An alteration, particularly frequent in acute infections, is char- 
 acterized by disappearance of the nucleus, so that the cell forms no 
 more than a uniform red mass. Such, for instance, is the case in 
 experimental infection by anthrax. 
 
 There may also be found lesions of the connective tissue. Among 
 these sclerosis is the most frequent. The sclerotic marrow often 
 observed in tuberculous individuals may be taken as a type. It is 
 yellow in color and firm. Sclerosis often coexists with cellular 
 proliferation; the two lesions are then sharply separated and are 
 produced in different regions of the medullary tissue. 
 
 The vessels at times present marked lesions of arteritis and 
 phlebitis. In five children who suffered from chronic gastroenteritis 
 and succumbed to bronchopneumonias, Haushalter and Spillmann 
 found marked lesions of endarteritis and periarteritis. 
 
 Finally, miliary tubercles may develop in the medullary tissue in 
 
INFLUENCE OF INFECTIONS UPON THE 0BQANI8M. ;;?? 
 
 oases of acute tuberculosis. These tubercle pr< enl the ordh 
 structure, and may be reproduced experimentally by inoculating 
 cultures of the tubercle bacillus into the bone-marrow. 
 
 Semiology of the Bone-marrow. The study of modifications in 
 the bone-marrow presents considerable importance from the stand- 
 point of general pathology. It reveals one of the defen ive pro- 
 cedures of the organism. It may appear less interesting from a 
 clinical standpoinl . The increased activity of the bone-marrow o 
 however, explain certain painful sensations experienced in the course 
 or in consequence of infections in the limbs, especially in the ju 
 epiphysial regions. It likewise accounts for the overgrowth of young 
 subjects in consequence of certain diseases, notably typhoid fi 
 It may even be questioned whether certain osseous deformities, 
 certain lesions of the skeleton, are not the consequence of the morbid 
 process of which the bone-marrow is the sent. Are nol the osteop- 
 athies of pneumonia, the osseous lesions of dyspeptic persons, and 
 notably the nodules of the second phalanges, connected with lesions 
 of the medullary tissue? Is not this tissue responsible for the 
 development of rachitis and osteomalacia? 
 
 That these remarks are not baseless is shown by the results yielded 
 by the study of typhoid fever. Various osteomedullary manifes- 
 tations have been observed as a result of this infection. 1 Among 
 the milder phenomena are the dull pains similar to those felt in the 
 so-called "fever of growths." It is probably due to the action of 
 diffused toxins. At a higher degree the patient complains of a fixed 
 pain which is the clinical expression of a microbic colonization. 
 Either resolution occurs or an exostosis develops. Finally, if the 
 microbe is more virulent, a focus of osteomyelitis is produced, at 
 times so slowly as to simulate a cold abscess. 
 
 A similar series of evolution is observed in a chronic infection, 
 viz., syphilis. Pains in the bones, exostoses, and gummata equally 
 point to an important participation of the medullary tissue. 
 
 The osteomedullary tissue may be the starting point of embolic 
 accidents. Osteomyelitis, proliferative inflammations of the bone- 
 marrow, liberate a certain amount of fat. This substance enters the 
 circulation, and, being arrested in the capillaries, notably in th< »s 
 the lung, may give rise to grave disorders. 
 
 The clinical study of the bone-marrow must be completed by 
 
 Achard. Manifestations osseuses de la fievre typhoi.de. Semaine m&L, 18 
 
378 I SFECTIOUS DISEASES. 
 
 hematological examinations. These examinations, by showing a 
 great number of myelocytes, enable us to affirm involvement of the 
 marrow. Two diseases in particular cause the passage into the 
 blood of these peculiar cells, which are never encountered therein 
 under normal conditions. One of them is lymphadenia, the influence 
 of which has long been known; the other is variola, which gives rise 
 to a myelocytosis so very characteristic that it may aid in establish- 
 ing a differential diagnosis. 
 
 \^' 
 
 The Spleen in Infections. 
 
 The important role played by the spleen in the defense of the 
 organism has only recently been understood. It appears now 
 demonstrated that this gland exerts a destructive action upon living 
 parasites and organic particles. Its chief function, however, is to 
 supply to the circulation, and thus send to distant parts of the 
 economy, cells capable of struggling against infectious agents. In 
 addition to this phagocytic role related to its richness in morpho- 
 logical elements, the spleen may also aid in modifying the chemical 
 constitution of the blood; it produces germicidal substances. This 
 protective role, however, important as it is, cannot be said to be 
 indispensable for the economy. Animals devoid of a spleen are still 
 capable of resisting infection, because there are many other organs 
 endowed with the same function. We shall cite but one example: 
 In variola, the reactionary modifications in the bone-marrow and 
 in the spleen are analogous; the same cells are produced by both 
 organs. 
 
 Infectious diseases almost constantly affect the spleen and in 
 most cases cause hypertrophy of this organ. This law suffers a few 
 exceptions. The liver is not altered, at least its volume is not 
 increased, in yellow fever, dysentery, and cholera; it is possible, 
 however, that its parenchyma does undergo modifications which 
 require minute investigations for their discovery. 
 
 The state of the spleen in typhoid fever has been a subject of 
 particular attention. Morgagni noted the hypertrophy of this organ 
 in the course of febrile diseases which may easily be related to 
 typhoid fever. Some authors went so far as to regard the alteration 
 of this gland the characteristic feature of typhoid fever, and described 
 epidemic and contagious splenitis. It is to be remarked, however, 
 that the spleen is not alone altered, but the other hematopoietic 
 glands are similarly involved. 
 
INFLUENCE OF INFECTIONS UPON THE ORGANISM 379 
 
 As is known, hypertrophy of the spleen occui in the middle ol 
 the first week of typhoid \'c\cv; it increases until the end of the 
 second week, und may be accompanied by intraparenchymatoufl 
 hemorrhages and terminate exceptionally in rupture of the organ. 
 The hypertrophied spleen is al firsl firm, hard, and red. At thu 
 stage the dominanl feature is congestion of the parenchyma, which 
 is so intense at certain points as to produce small hemorrhagic foci. 
 The cellular lesions are not pronounced. Siredey noted only a 
 multiplication of the cells of the Malpighian corpuscles. In the 
 second stage — i.e., from the twelfth to the thirtieth day -the spleen 
 in some cases remains firm and hard ; oftener it i- -<>i't . and "n section 
 it presents small points which are due to the prominence "I' the 
 corpuscles of Malpighi. The latter contain, as normally, lympho- 
 cytes. This variety is mixed, however, with numerous mono- 
 nuclear and even polynuclear cells. The cells of the pulp are tume- 
 fied, voluminous, and generally filled with the detritus of red and 
 white blood corpuscles. They have the characters of mononuclears, 
 with a small nucleus situated at one of the poles of the cell. Finally, 
 the pulp, like the corpuscles, contains nodules formed of necr 
 cells. 
 
 These modifications, some of which represent reactions and others 
 lesions of the organs, are not peculiar to typhoid fever: they are 
 encountered, in various degrees, in the most varied infections, even 
 in those which remain local. 1 
 
 Among the infections which most frequently give rise to hyper- 
 trophy of the spleen we may cite typhus fever, acute tubercul 
 and the eruptive fevers, notably scarlatina. 
 
 Special mention is due to variola. Since the researches of Golgi 
 and of Ponfick it is generally admitted that the appearance of the 
 spleen is not the same in the suppurating and the hemorrhagic types 
 of this infection. The organ is said to be hypertrophied in the 
 former, while in the latter it is believed to be small, hard, and black. 
 The examinations, however, made by Dr. Weil and myself during 
 the last epidemic render this conclusion inadmissible. The hyper- 
 trophy of the spleen is related not to the clinical type, but to the 
 intensity of reaction. For this reason it is more frequent in the 
 suppurating type. Thus in sixteen fatal cases of confluent variola 
 the spleen was hypertrophied sixteen times. In twelve cases of 
 
 1 Bezancon. Contribution a l'eaule de la rate dans les maladies infectieuses. These 
 de Paris, 1S95. 
 
380 IXFECTIO US DISEASES. 
 
 hemorrhagic variola it was hypertrophied but four times. In none 
 of the latter scries, however, have we found any peculiar appearance. 
 Contrary to Golgi's opinion, histological examination revealed no 
 f inii lamental differences. What is truly characteristic of hemorrhagic 
 variola is the, presence of nucleated red globules. In brief, the 
 modifications undergone by the cells of the spleen are similar to 
 those observed in the other hematopoietic organs, notably in the 
 bone-marrow. Under the influence of variola the spleen is thus 
 found to contain cellular elements which exist there only during 
 fetal life and which seemed to have disappeared forever shortly 
 after birth. Infection has revived a past state. 
 
 Gerhardt has shown hypertrophy of the spleen to be of frequent 
 occurrence in pneumonia. The same may be observed in erysipelas, 
 which resembles pneumonia in certain features of its evolution. 
 Finally, the spleen is small in the algid period of cholera; it becomes 
 voluminous if typhoid manifestations supervene. 
 
 Chronic infections do not spare this gland. It will suffice to refer 
 to what occurs in syphilis during the secondary period, and more 
 especially in malaria. 
 
 It is well to note that in all the organs and tissues in which pig- 
 ment is encountered the latter is found in the vessels. In the spleen 
 and bone-marrow r , however, the pigment occupies the cells. It is 
 in these localities that it seems to take its origin at the expense of 
 red blood globules altered and destroyed by the hematozoa of 
 malaria. 1 In this connection recurrent fever deserves special men- 
 tion. During the periods of apyrexia the spirilla accumulate in the 
 spleen, while the other viscera are free from them. Metchnikoff 
 and Soudakewitch, 2 who pursued researches on monkeys, have seen 
 the parasites devoured by the macrophages of the spleen. This is 
 a highly remarkable example of phagocytosis. This result seems 
 to be confirmed by the experiments of Soudakewitch, who learned 
 that monkeys deprived of their spleens, unlike normal monkeys, 
 succumbed to inoculation of the spirilla. This has been contradicted 
 by Tiktine, who repeated the experiments and denies all influence to 
 splenectomy. He thinks that the different results obtained by the 
 former experimenter are due to the fact that he operated in winter, 
 when the slightest lesion is sufficient to cause death to monkeys. 
 
 1 Kelsch and Kiener. Trait6 des maladies des pays chauds. Paris, 1SS9. 
 
 2 Soudakewitch. Recherches sur la fievre r6currente. Annales de PInstitut Pasteur, 
 1891, p. 515. 
 
INFLUENCE OF INFECTIONS UPOh THE ORGANISM. :>,*) 
 
 The highly Interesting work of Courmonl and Duffau 1 teach* 
 that the resistance of animal varie con iderably according to the 
 microbe employed and the time elapsed ince the extirpation of the 
 spleen, [f the pyogenic staphylococcus i employed the extirpation 
 first diminishes the resistance of the animate rabbits, dogs, etc.; 
 subsequently ii increases it. Willi the streptococcus the results 
 are diametrically opposed to the former: animate in which the spleen 
 had been extirpated two to eighl days proved more resistanl than 
 the controls; on the contrary, those which were operated upon 
 twenty-seven to forty-eighl days after splenectomy proved t" be 
 more susceptible Lastly, with the bacillus pyocyaneus the animate 
 operated upon succumbed more rapidly whatever the date of o] 
 tion. These experimental facts indicate once more tin' danger of 
 hasty generalizations and explain a certain number of contradictory 
 results. 
 
 Role of the Spleen in the Production of Germicidal Substances. 
 In order to explain tin 1 action of the spleen upon microbes the 
 modifications in phagocytosis were first invoked. Such was the 
 opinion of Gamaleia. The same view was held by Bardach. A- i- 
 known, the latter author contends that extirpation of the spleen 
 lessens the resistance of animals by suppressing an important centre 
 of microbic destruction. He finds confirmation of his ideas in the 
 following experiment: He injected charcoal powder into the veins 
 of four dogs. Two days later he inoculated the animals with 1 c.cm. 
 of an anthrax culture; all the dogs succumbed, and microscopic 
 examination demonstrated that the cells of the spleen, liver, and 
 bone-marrow were crowded with charcoal particles, and therefore 
 were absolutely incapable of ingesting the microbes. 
 
 At the time these first researches were published the protective 
 action of the blood serum was scarcely recognized. Since innumer- 
 able investigations demonstrated beyond doubt the importance of 
 germicidal properties of the fluids of the organism, the question 
 concerning the spleen has been taken up. The researches of Hankiir 
 proved the presence in the spleen of a strongly germicidal globulin. 
 Montuori next undertook this new problem. 3 and reported highly 
 
 1 Courmont and Duffau. Du role de la rate dans les infection.-. Archives de m<ki. 
 expe>im.. 1S9S. p. 431. 
 
 2 Hankin. A bacteria-killing globnline. Proc. Roy. Soc. London, xlviii. p. 93. 
 
 3 Montuori. Influenza dell ablazione della mitza sur potere microbicida del sangue. 
 La Riforma med.. 1S93. i. p. 472 and 4S.3. 
 
: i s 2 I NFE CTIOl rS JDISEA SES. 
 
 interesting facts which throw light on many obscure points. His 
 experiments demonstrated the hematopoietic function of the spleen. 
 This gland may. however, be supplemented by other organs, since, 
 a few months after extirpation of the spleen, the blood regains its 
 germicidal power. Montuori completed his experiments by investi- 
 gating the chemical modifications which occur in the blood of animals 
 with extirpated spleens. He recognized that the bactericidal power 
 of the normal blood is due, as was shown by Ogata, to a true ferment. 
 This ferment, which is very abundant in the blood of the spleen, is 
 absent from the blood which has lost its germicidal power as a result 
 of splenectomy. 
 
 While animals deprived of the spleen are more sensitive to certain 
 viruses, they become more resistant to others. In the latter case 
 the germicidal power of the blood increases and acquires the property 
 of depriving microbes of their virulence. By making comparative 
 cultures of the staphylococcus in the blood of normal animals and 
 others without spleens Courmont and Duffau established that the 
 microbe develops better and becomes exalted in the serum of those 
 animals in which the spleens were extirpated. With the strepto- 
 coccus the results were reversed; the microbe was attenuated. On 
 the other hand, Blumreich and Jacoby found that the serum of 
 splenectomized animals diminished the virulence of pyocyaneus 
 diphtheria and cholera bacilli, and this power of the blood accounts 
 for the increased resistance observed w^hen splenectomized animals 
 are inoculated. It is to be noted, however, that the chemical modi- 
 fications of the fluids are not the only factors to be taken into account; 
 the authors attribute an important influence to the increased leuco- 
 cytosis which coincidently takes place. 
 
 The Lymphatic Glands in Infections. 
 
 The lymphatic system is provided with numerous protective 
 organs, close follicles, and ganglia, which seem to play a double role : 
 to arrest, retain, and modify the figurate elements and soluble 
 products brought to them by the lymphatic capillaries ; to pour into 
 the blood cells and soluble products useful for the organism. In 
 order to fulfil their functions the follicles and ganglia are arranged 
 in chains, and are most numerously supplied to those regions most 
 liable to microbic invasions. They are relatively less numerous at 
 the root of the limbs, especially of the upper extremities. Their 
 number in the lower extremities is particularly multiplied with a 
 
INFLUENCE OF INFECTIONS UPON THE ORGANISM. 
 
 view to protect- the economy against the bacteria coming by way 
 of the externa] genital organs and margin of the anus. Lik< 
 the follicles at the base of the tongue, pharynx, and ton il form a 
 lymphatic ring with the function of combating the bacteria of the 
 mouth and throat, Less abundanl in the esophagi] and th<- 
 stomach, the lymphoid organs are distributed with greal profusion 
 throughout the intestine, where they constitute the solitary follicles 
 and Peyer's patches. In the appendix, which is mosl liable to 
 attacks of infections agents, the lymphoid system is in"-' richly 
 developed, forming :i veritable glandular mass which has justly been 
 compared to the tonsil. 
 
 Beyond this first line of defense are Bituated the glands, which 
 represent as many fortresses ranged one behind the other. I' i- 
 .inl cresting to note that their number is in proportion to the danger 
 of infection in each region. 
 
 The multiplication of the ganglia around the bronchi, a1 the rool 
 of the lungs, and especially in the mesentery, is particularly notable. 
 
 In a great number of circumstances bacteria of all kinds may pass 
 through the skin and particularly the mucous membranes. They 
 are arrested by the ganglia, in which they sojourn without giving 
 rise to any reaction or disturbance. Loomis and Pizzini discovered 
 tubercle bacilli in the tracheobronchial and mesenteric gland- of 
 apparently normal individuals. Manfredi and Perez 1 examined the 
 lymphatic glands in eighty-five animals and detected bacteria in 
 seventy-five of them. The same researches made upon three human 
 cadavers gave positive results in each case. The subcutaneous 
 glands are those most commonly infected : next, the tracheobronchial 
 glands, while the mesenteric glands are generally sterile. Among 
 the species most frequently met with are various sarcinae, the staphy- 
 lococcus aureus or albus, the mesenteric bacillus, a pseudotyphoid 
 bacillus, etc. 
 
 The microbes enclosed in the lymphatic glands undergo notable 
 alterations. Manfredi demonstrated that they gradually lose their 
 virulence and are finally destroyed through a peculiar procedure 
 which seems to be different from the means employed in other parts 
 of the organism, but which is not yet well understood. These modi- 
 fications are slowly effected. Xot infrequently, therefore, the germs 
 may persist for a long period of time, this period varying with the 
 
 1 Perez. Modo di comportarsi del sistema ganglionare linfatico rispetto ai microor- 
 gamsmi, Labori di Laboratories publicati dal L. Manfredi. Palermo. 1S97. vol. iii. 
 
384 IXFECTIO US DISEASES. 
 
 microbe and the animal employed in the experiment. For instance, 
 the staphylococcus aureus survives forty days in the guinea-pig and 
 thirty days in the dog. It is interesting to note that all other parts 
 of the organism no longer contain any microbes, while some are still 
 present in the lymphatic glands. This persistence of germs explains 
 certain relapses, notably those of eiysipelas. I believe the same 
 fact accounts for the morbid incidents occurring during convales- 
 cence from scarlatina. The anginous lesions which characterize 
 the onset of this infection permit the penetration of the buccal 
 streptococcus into the lymphatic network; the cervical glands are 
 congested. Later, at the moment of convalescence, a new infection 
 of ganglionic origin may occur; then the patient has fever and 
 complains of painful adenopathia. In some cases the ganglionic 
 infection remains uncomplicated; in other instances it is followed 
 by more or less serious events, and notably an attack of nephritis. 
 
 The lymphatic glands, like all the dependencies of the lymphatic 
 system, are especially developed during childhood. In fact, it is 
 at this period of life that the danger of infection is greatest. The 
 Emphatic system is, therefore, most vigilant and enjoys its greatest 
 functional energy. The slightest lesion causes ganglionic congestion. 
 When an agent is highly pathogenic it freely traverses the lymphatic 
 system and produces a general infection without the development 
 of any adenopathy. The latter manifestation is likewise wanting 
 or remains unnoticed when the agent is but slightly virulent, It is 
 in infections of medium intensity, therefore, that the ganglionic 
 phenomena must be studied. The development of adenopathies 
 depends upon two factors: the nature of the pathogenic agent and 
 the state of the individual. With individuals whose organisms are 
 incapable of energetic reaction, adenopathy is little marked; it is 
 insufficient. In the contrary case, especially in children, it is too 
 energetic and expressed by lesions which survive the cause, and may 
 give rise to numerous incidents during and after the infectious 
 process; such, for instance, is the case in tracheobronchial adenop- 
 athies compressing the respiratory passages and the nerves of the 
 neighborhoods. 
 
 Histological Study. The presence of bacteria causes in the 
 lymphatic glands modifications well studied by Drs. Bezancon and 
 Labbe, who have made numerous experiments on this subject. 
 The effects vary according to the activity of toxins. If the latter 
 are of medium energy, reactionary phenomena are produced. If 
 
INFLUENCE OF INFECTIONS UPON THE ORGANISM. 
 
 they are extremely energetic, necro i occui ,&\ times with astonish- 
 ing rapidity. In fifty minutes the diphtheritic toxin gives rise to 
 cellular degenerations and fibrinoid exudate . It a little serum be 
 injected at the same time or I wenty-four hours previou ly, reaction- 
 ary phenomena appear (Bezancon and Labbe , 
 
 The reactionary phenomena are grouped under three division 
 congestion, proliferation of the fixed cells, and arrival of polynuclear 
 cells. 
 
 Congestion is at limes so intense as to provoke hemorrhage. Such 
 is the ease, particularly, in pneumonia, anthrax, and diphtheria. 
 The fixed and endothelial cells sunn become swollen and form macro- 
 phages, which mingle with the leucocytes, while the lympIlOC 
 
 continue to multiply in the follicles by karyokinesis. At the same 
 time the polynuclear cells arrive. It is known thai the gland con- 
 tains normally no other than polynuclear cells and lymphocytes. 
 The polynuclears arrive through the afferent lymphatics vessel and 
 the bloodvessels — i. c, the capillaries. This leucocytosis occurs 
 early; it appears three-quarters of an hour after bacterial inoculation. 
 then it increases progressively, to again decline toward the eighteenth 
 hour. Those modifications are especially marked in the gland- 
 corresponding to the invaded point, but also occur with the same 
 characters in distant glands, only with less intensity. 
 
 Beside these defensive reactions we must note the necrotic pro« 
 The cells undergo hyaline degeneration, especially in slow c 
 The dilated lymphatic channels are filled with pale, large cells with 
 a vitreous protoplasm and a colorless nucleus. The polynuc 
 leucocytes that have migrated into the glands are also involve.!, 
 though in a different manner; their nucleus is fragmented and r< - 
 duced to fine granules. The follicular system, the most resisting 
 part, also finally undergoes degeneration, notably in diphtheria. 
 Lastly, the bloodvessels undergo arteritis and hyaline degeneration, 
 and their lumina may become obliterated by thrombosis 
 
 The inflamed gland may gradually recover its normal condition or 
 remain enlarged. In the latter case it occasionally assumes the 
 appearance of a tubercular lesion, but seems to be due to the persist- 
 ence of pyogenic cocci. In other instances the process procee - 
 suppuration. All parts of the gland are not invade* 1 simultaneously : 
 the follicular system resists for a long time. 
 
 Finally, the diseased cells may not be replaced, and then the 
 inflammatory lesion terminates in sclerosis. 
 
 25 
 
386 ISFECTIO US DISEA SES. 
 
 Adenopathies in Variola. We cannot review all the infections 
 which affect the lymphatic glands. We must, however, direct the 
 attention of the reader to variola, which, from the standpoint under 
 consideration, is extremely important, and which has hitherto been 
 overlooked. The only work on this subject is Lelandxis' thesis, 
 inspired by Enipis. The frequency of ganglionic hypertrophy in 
 variola has been pointed out by this author, who considers it an 
 element of favorable prognosis. 
 
 The investigations which were pursued with Dr. Weil during the 
 late variola epidemic in Paris showed us that enlargement of the 
 lymphatic glands is subject to the same rules as hypertrophy of the 
 spleen. It is very marked in pustular types of smallpox, very 
 slight or nil in hemorrhagic types. The enlarged glands are gener- 
 ally painless, and hypertrophy is apparent from the beginning of 
 the disease, increases during the period of eruption, persists during 
 suppuration, and then declines and disappears. The axillary and 
 inguinal groups are most frequently involved, although the topog- 
 raphy of the exanthema does not explain this localization. 
 
 The histological features peculiar to variolar adenopathy are the 
 presence in the lymphatic vessels and around the follicles of cellular 
 forms similar to those found in the bone-marrow, notably neutrophilic 
 myelocytes, a few basophilic myelocytes, and, in some instances, 
 eosinophilic myelocytes. Finally, a few giant cells, and, in hemor- 
 rhagic types, nucleated red corpuscles may also be encountered. 
 This peculiar evolution (which had hitherto been observed only in 
 leukemia) may extend to the cellular tissue surrounding the glands. 
 In sections its appearance is similar to that of the bone-marrow. 
 The latter fact further emphasizes the analogy of the process to 
 that which occurs in leukemia. It may, therefore, be assumed that 
 the cellular tissue itself acquires a cytogenetic activity, and that, 
 like the spleen, the glands, and the bone-marrow, it produces vari- 
 ous leucocytes. This process has not thus far been observed in any 
 other infection than variola. It would be interesting to take up the 
 question from a general standpoint and investigate the state of the 
 connective tissue in all infections. I am convinced that very pro- 
 nounced modifications will be observed. 
 
 Syphilitic and Tubercular Adenopathies. Chronic infections 
 often give rise to ganglionic lesions. Syphilis is a familiar illustra- 
 tion. The chancre produces enlargement in a group of lymphatic 
 glands among which one becomes remarkable for its size. This 
 
INFLUENCE OF INFECTIONS UPO& THE ORGANISM. 
 
 adenopathy is lacking only in exceptional and g< nerally vi 
 cases. During the secondary period multiple adenopathies occur 
 and are of considerable semiological importance. They often coin- 
 cide wifh hypertrophy of other parts of the lymphatic system, 
 especially in women, whose tonsils and 3pleene become lil • 
 enlarged. During the tertiary period germs may be found in them, 
 these germs presenting no particular character of evolution. 
 
 Tubercular adenopathies may be generalized. This condition U 
 mainly observed in young children. Micropolyadenitis ie strongly 
 suggestive of tuberculosis and more readily detected than hyper- 
 trophic conditions of the liver and spleen. This peculiar evolution 
 is comparable to whal is observed in laboratories. Tuberculosis 
 caused by inoculation into guinea-pigs behaves in exactly the same 
 manner. It is first expressed by tumefaction of the glands corre- 
 sponding to the infected point, and then all the glands of the economy 
 are gradually involved, and finally the abdominal viscera. In some 
 cases the thoracic organs also are affected. The lymphatic system 
 is thus seen to he well designed to arrest the course of invading 
 bacteria, although in some rare instances it may aid in their spread, 
 as is shown by the investigations of Ponflck on the thoracic duct. 
 
 It is interesting to remark that actinomycosis, a disease so closely 
 allied to tuberculosis, does not affect the lymphatic glands. 
 
 Humoral Modifications of Lymphatic Origin. It is not merely by 
 phagocytic action that the lymphatic glands protect the system. 
 It seems to be demonstrated that these small organs secrete germi- 
 cidal and antitoxic substances. The investigations of Pfeiffer and 
 Marx show that, during the immunization of animals, these glands 
 produce antitoxins which are carried into the circulation. It is con- 
 ceivable that the glands of infected or vaccinated animals may be 
 utilized in the treatment of certain diseases. Manfredi has ma< le some 
 attempts in this direction and found that the ganglionic juice of tuber- 
 culous goats hindered the development of this disease in guinea-pigs. 
 
 The Thymus in Infection. 
 
 Anatomical and Physiological Considerations. In its histo- 
 logical structure the thymus resembles the lymphatic glands. It 
 differs from them in its embryogenic origin. 1 The thymus has at 
 
 1 Ghika. Etude sur le thymus. These de Pari.-?. July. 1901. This is a very complete 
 monograph containing a great number of histological and experimental researches pur- 
 sued in our laboratory. 
 
388 IXFECTIOUS DISEASES. 
 
 first an epithelial structure; later it assumes a lymphoid character 
 as a result of direct transformation of the primary elements. We 
 found this transformation completed in a fetus of three months. 
 In the fetus of six months appear peculiar formations — the corpuscles 
 of Hassall — the aspect of which is absolutely characteristic. From 
 the sixth month onward and until the period when regression sets 
 in the thymus undergoes no appreciable modification in structure. 
 The cells contained in the fibrillary network are mostly lymphocytes ; 
 besides these there are also some neutrophilic and fewer eosinophilic 
 
 Fig. 26. 
 
 Normal cat, one month. Reticulum quite visible. Numerous lymphocytes. Tra- 
 becular cells with large clear nucleus and distinct nucleolus. Large corpuscles of Hassall. 
 Epithelioid fragments in the centre. Numerous vessles filled with blood corpuscles. 
 
 polynuclears, non-granular mononuclears, mastzellen, granular mono- 
 nuclears or eosinophile, basophile, or neutrophile myelocytes, rarely 
 giant cells, and elements resembling nucleated red globules. Finally, 
 there are also epithelioid cells and large cells with vesicular nucleus. 
 Hassall's corpuscles have an extremely variable appearance. They 
 are occasionally formed by a single enormous cell; the chromatin 
 of the nucleus presents the most varied figures. 
 
INFLUENCE OF TNFE0TI0N8 UPON THE ORGANISM. 
 
 The thymus grows smaller with age. W i oon invaded b 
 profuse cellulo-adipose ma , bu1 doe no1 completely disappear, 
 The corpuscles persist for a long time, but di appear in the very aged. 
 
 In animals this gland present a structure very much similar to 
 the human. The same cellular form are found; the only essential 
 difference is in the number and appearance of Hassall's corpuscles. 
 In the rabbit, guinea-pig, and ral these corpuscles are extremely 
 rare, and are composed mostly of a 3ingle large cell. The cat, on 
 the contrary, has very clear corpuscles, and while it is alwaj 
 differentiate in sections a thymus of a child from thai of a rabbit, 
 guinea-pig, or rat, it is almosl impossible to distinguish the human 
 thymus from that of a cat. In frogs and hibernating animals the 
 thymus is voluminous in the summer and small in winter. Path- 
 ology teaches us thai this gland, which is highly developed in well- 
 nourished children, atrophies in feeble or cachectic children. I- the 
 atrophy the cause or the effecl of the nutritional disorders? 
 
 To solve this problem experimentation should be resorted to. A 
 great many times, therefore, the gland has been extirpated. On 
 the other hand, attempts have been made to aso rtain the efifec 
 injection, ingestion, and inoculat ion of extract.- of this gland. With- 
 out wishing- to dwell upon the details of the experiment- related in 
 the thesis of Dr. Ghika, we believe thai facts warrant us in con- 
 cluding that the thymus plays an important parr in nutrition. In 
 order to obtain clear evidence very young animals musl be operated 
 upon. Our best experiment was made upon a cat fifteen days old. 
 The extirpation of the thymus was complete. The animal, which 
 weighed 485 grams, increased in weight to 635 grams in twenty- 
 two days. An animal of the same litter, kept as control, weighed 
 then 890 grams. From this moment onward the operated one 
 began to lose flesh. At the end. of thirty-five days it succumbed 
 in a state of profound cachexia. It then weighed 430 grams, 55 
 grams less than at the beginning of the experiment, while the weight 
 of the control reached 1090 grams. 
 
 Among the symptoms observed in animals in which the thymus 
 is extirpated we may mention, besides emaciation, arrest of growth, 
 anomalies of the skeleton, especially costal deformities, trembling, 
 stupor, weakness, and. in some cases, paralysis. These various 
 manifestations may be slight or absent as the result of supplemental 
 activity on the part of other hematopoietic organs, at least in certain 
 cases. At the necropsy of the animals experimented on we found 
 
390 IXFECTIOUS DISEASES. 
 
 the bone-marrow red and proliferated; histological examination 
 demonstrated its vicarious activity. 
 
 Besides being a gland with an internal secretion the thymus has 
 an important cytopoietic function. Its structure, being similar to 
 that of all adenoid tissues, leads to the conclusion that it forms 
 white blood corpuscles. The experiments pursued on this question 
 have not given very clear results, probably because other hemato- 
 poietic organs rapidly come into play and prevent the development 
 of manifestations. 
 
 Histological Modifications of the Thymus in Infections. The 
 histological study of the thymus leads to clearer conclusions. In a 
 great variety of physiological or pathological circumstances cellular 
 proliferations entirely comparable to those occurring in the bone- 
 marrow are observed. 
 
 Cellular proliferation takes place in inanition, intoxications, and 
 infections. We have been able to study these in animals intoxicated 
 by phosphorus or carbonic oxide as well as in those inoculated with 
 the most varied microbes or poisoned by the toxin of diphtheria, 
 We have found the same modifications in the thymus glands of 
 children dead from variola, measles, erysipelas, whooping-cough, 
 syphilis, and tuberculosis. 
 
 This study of modifications of the thymus in infections is entirely 
 new. 1 The only information found in authoritative works consists 
 of a few r macroscopic examinations. From these it might be inferred 
 that the thymus does not react in infections or that it occasionally 
 undergoes partial degenerations. This opinion does not seem to us 
 acceptable. The thymus is constantly modified in the course of 
 various infectious processes. It may be seen with the naked eye 
 that the gland is enlarged, red, and congested. It may even be the 
 seat of hemorrhages. In other instances it may be pale and anemic. 
 Under the microscope modifications in the fibrillary network, vessels, 
 cells, and Hassall's corpuscles can be seen. The fibrillary substance 
 is only slightly affected, at least when the process is acute. In 
 some cases it becomes thickened. The bloodvessels are congested, 
 and their walls are often infiltrated with yellow cells. At certain 
 points thromboses and hemorrhages are observed. The principal 
 modifications are found in the cellular elements. The lymphocytes 
 
 1 Roger and Ghika. Recherches sur l'anatomie normale et pathologique du thymus, 
 XHIe Congres intern, de m^decine, section de pathologie generate, p. 219. Journal de 
 phys. et pathol. generate, Sept., 1900. 
 
INFLUENCE OF INFECTIONS UPON THE ORGANISM. 301 
 
 and the small mononuclears alwayi form the fundamental pari of 
 the gland. Bui a greater number of large mononucleai inter- 
 mediate forms, and polyneutrophilei are me1 with. The poly- 
 eosinophiles and nucleated i*< ** I globulei are • , il" more numerous. 
 Moreover, there appear elements which are either absenl or rare in 
 the normal thymus— mastzellen, myelocytes, leucocytes with mixed 
 granulations, and, in animals, pseudoeosinophiles. There are also 
 encountered two special varieties of non-granular mononuclears. 
 Some are large cells measuring from \~>," to -"//, with volumin- 
 
 l i... 27. 
 
 
 Child of two months, dead from erysipelas of the face. Rei 
 dating the lymphocytes. Numerous granular forms. Cystic Hassall's 
 with colloid contents in the form of onion bulbs, unicellular or paucicellular. 
 
 ous excentric nucleus; the protoplasm stains strongly with thionin. 
 but faintly, if at all, with eosin. The others are equally large cells 
 with a dark protoplasm and hardly visible nuclei. The former 
 resemble plasma cells, the latter the irritation cells of Tiirck. 
 
 Besides these functional modifications, lesions also occur. The 
 cells may undergo granular, vacuolar, or fatty degeneration, coagula- 
 tion necrosis, and karyolysis. At times necrotic foci are formed in 
 which all the elements are destroyed. 
 
392 IXFECTIO US DISEASES. 
 
 All infections do not act with the same intensity, but all do act. 
 
 Erysipelas is one of the diseases the action of which is most 
 marked. The thymus is remarkable for the development of numer- 
 ous granular myelocytes. 
 
 Histological examination of a certain number of thymus glands 
 always reveals the existence of sclerotic lesions in some of them. 
 Ghika examined sixty-four glands, and found sixteen of them 
 sclerosed. In eleven of the cases the lesions were very pronounced. 
 
 Fig. 2S. 
 
 
 ■■ ■ \Vs^>& 'v \5— r :> "-■■$.'■*, " ■ '.-''."'V 
 
 * 
 
 The same preparation as in the preceding figure, more highly magnified. Very large 
 corpuscles of Hassall, containing cells, cell fragments, and colloid substance. The wall 
 is formed of epithelioid cells, which are clearly continued on the right side with the 
 trabecular cells. In the left lower corner is seen a large cell composed of a clear nucleus 
 and rounded protoplasm, containing fine eosinophile granulations disposed in concen- 
 tric circles. 
 
 These sclerotic lesions of the thymus are occasionally observed 
 in children dead of acute diseases. In such instances it is quite 
 certain that the lesions existed previous to the occurrence of the 
 acute malady. They sometimes depend upon involution of the 
 gland. When, however, the lesions are found in young children 
 they must be attributed to s3 T philis or some antecedent infection, 
 to bad hygiene, athrepsy, or some hereditary taint. Syphilis, tuber- 
 
INFLUENCE OF INFECTIONS UPON THE ORGANISM. 
 
 culosis, alcoholism, and defective nutrition of the parenl are the 
 most frequent causes. 
 
 Primary Infection of the Thymus. Although the thymu 
 almost invariably affected in the course of infectious di ea e . il U 
 seldom the seal of a primary affection. There are bul few facte 
 
 013 record. 
 
 VV. Wittich has reported the case of a young man, aged eighteen 
 years, who was suddenly seized with dyspnea and retrosternal pain, 
 and who was soon attacked by hydrothorax and ascites. He suc- 
 cumbed to a paroxysm of dyspnea. The autopsy revealed an enor- 
 mous thymus filled with purulenl cavities. The pericardium 
 healthy. Demnie published a similar case. In a child of two and 
 a half months was found a purulenl transformation of the thymus, 
 which was manifested during life by a red and painful tumor occupy- 
 ing the lower pari of the neck. Schlossmann, Helm, and Biederl 
 have recorded cases of rapid death preceded by paroxysms of suffo- 
 cation iii young children. The necropsy showed a voluminous, 
 inflamed thymus (Biedert), or one infiltrated with pus. In Schloss- 
 mann's case bacteriological examination revealed a microbe anal- 
 ogous to Fischer's pyobacterium. Demme has related an incon- 
 testable case of primary tuberculosis of the thymus in a little girl. 
 Syphilitic gummata and sclerosis may develop in this gland as well 
 as in any other organ. 
 
 The Thyroid Gland in Infectious Diseases. 
 
 The only lesion of the thyroid that has been described in infections 
 is suppurative thyroiditis. This involvement is so rare that, if it 
 was the only one that may occur, the participation of this gland in 
 infectious processes should be regarded as exceptional. Systematic 
 examination of the thyroid in all the necropsies which we made 
 during one year led us to a different opinion. Far from being 
 indifferent in the presence of infection, this gland always reacts 
 more or less energetically, and this reaction is expressed by histo- 
 logical modifications which we have studied with Dr. Gamier. 1 Let 
 us first briefly consider certain details of normal histology. 
 
 1 Roger and Gamier. Infection thvroidieime experimentale. Soc. de biol., Ocl 
 1S0S. Action du bacille typhique snr la glande thyroide. Ibid. La glande thyroide 
 dans les maladies Lnfectieuses. Presse medicate, April 19, 1899. Recherches experi- 
 mentales sur les infections thyroidiennes. Ibid.. August 9, 1900. 
 
394 INFECTIOUS DISEASES. 
 
 Remarks on Normal Histology. The thyroid apparatus is com- 
 posed in man, as in other mammals, of two distinct parts — the 
 thyroid gland proper, described in all classical treatises, and the 
 parathyroids — small glands discovered by Sandstrom in 1880, the 
 physiological importance of which was proved by Gley in 1892. 
 
 The structure of the thyroid is not the same in the adult and in 
 children. Defaucamberge was the first to show this difference in 
 
 Fig. 20. 
 
 
 ' c ^' 
 
 
 
 
 
 
 V 
 
 3 
 
 Thyroid gland in children. This figure and the following three are taken from the 
 work which we published with Dr. Garnier (La glande thyroide dans les maladies 
 infectieuses), Presse mddicale, April 19, 1S99. 
 
 1889, and distinguished two types: the truly glandular type, which 
 is found in the child and is more or less marked until puberty, and 
 the colloid type, which corresponds to the normal state in adults. 
 The thyroid gland in children is formed of distinct lobules, separated 
 from each other by connective tissue. (Fig. 29.) 
 
 This tissue enters the lobules and divides them into smaller depart- 
 ments, each of these containing two or three vesicles. The connective 
 
INFLUENCE OF INFECTIONS UPON TEE ORGANISM, 
 
 tissue contains numerous nuclei and an abundanl ba emenl sub- 
 stance. Each vesicle i. lined bya layer of lowly organized cella; the 
 centre is occupied by colloid iri.it ter. 
 
 In the thyroid gland of the adull the mosl Btriking feature us the 
 complete absence of the lobulated tructure. (Fig. 30.) The nol 
 abundant connective (issue is reduced to fine trabecular running 
 between the vesicles. The glandular parenchyma appears to be 
 
 )■ :::■■- 
 
 t.K i 
 
 I i.. 30 
 
 ..■;/ 
 
 ..-/,:.--.• 
 
 Thyroid gland of a normal adult. 
 
 formed simply by juxtaposition of closely arranged colloid mass ~. 
 or is separated here and there by a cellular mass. 
 
 The parathyroids are small organs situated in the neighborhood 
 of the thyroid, but differing from it in origin and structure. They 
 are chiefly met with near the point at which the thyroid arteries 
 enter the gland. The}- vary in number and size. They do not 
 present the vesicular arrangement or the colloid substance of the 
 thyroid. They are surrounded by a capsule of connective tissue 
 
396 
 
 INFECTIOUS DISEASES. 
 
 covering the whole gland and extending into its interior partitions, 
 which divide it into irregular departments. The meshes thus 
 formed are filled with rows of cubical epithelial cells with well- 
 stained nuclei and surrounded by a profuse granular protoplasm. 
 These cells are pressed one against the other and exactly applied 
 on the one hand to the connective tissue wall and, on the other, to 
 the neighboring row. 
 
 Fig. 31. 
 
 * m* 
 
 
 ;S «■* £* 
 
 &■>$%&*■ 
 
 ; '- % ' 
 
 
 Thyroid gland of a man dead from scarlatina. Considerable dilatation of vessels. 
 Trains of colloid matter surrounding the vesicles. 
 
 General Characters of the Thyroid in Acute Infections. When 
 examined with the naked eye the gland appears enlarged. While 
 normal^ its weight is about 25 grams (1 ounce), we found it in 
 seven cases to reach from 37 to 71 grams (1£ to 2\ ounces). The 
 color is changed from its normal hue — that is, yellowish — into red, 
 sometimes blue. The connective tissue is only slightly modified 
 and usually undergoes no pronounced alteration. At times,' how- 
 
INFLUENCE OF INFECTIONS UPON THE ORGANISM. 397 
 
 ever, especially in children, il eem bo contain a greater number ol 
 nuclei than normal. The pre ence of colloid lib tance oul ide the 
 vesicles changes the general appearance of the gland and may lead 
 to the belief thai the connective ti uei hypertrophied. (Fig. 31 , 
 This colloid substance dilates the lymphatic pacef of the gland and 
 produces a more or less complete network, the mesne* of which are 
 filled with vesicles. The vessels are dilated. There is ometimes 
 arteritis and phlebitis. The inflammation of the vessels, howi 
 
 Ik;. 32. 
 
 v :■ - ■ 
 
 
 •; 
 
 
 
 
 . 
 
 
 •V-^v » ... \ • - 
 
 
 ' -}; v , ! v ' - 
 
 _ • 
 
 Thyroid gland of an adult dead from scarlatina. Lobule completely transformed; 
 the vesicles contracted and crowded with cells; the thyroideal tissue is still recognizable 
 by a few dilated vesicles at the border of the lobule; the colloid substance no longer 
 takes eosin. 
 
 presents nothing particular. The vesicles are commonly smaller 
 than normal. Their composition is often profoundly modified: some 
 of them no longer contain any colloid substance, and their centre is 
 occupied only by cells in course of degeneration. In many cases 
 the protoplasm of several cells at the centre of the vesicle is fused 
 in a finely granular mass in the midst of which are seen degenerated 
 nuclei. On the other hand, some vesicles still contain a certain 
 quantity of normal colloid substance in the midst of desquamated 
 
398 IXFECTIO US DISEASES. 
 
 cells. When the lesions are very marked (Fig. 32) the secretion of 
 the colloid matter seems to be hindered or replaced by a few granu- 
 lations. 
 
 We have histologically examined the parathyroids in three cases 
 of scarlatina and in one case of diphtheria. Only in two of the 
 casi is were they found to be altered. The most important alterations 
 were observed in the case of a woman who died from scarlatina. 
 While the thyroid had deviated but little from the normal type, the 
 glandules, four in number, presented interesting modifications. The 
 connective meshes were half empty; the cells had lost the arrange- 
 ment in regular rows and were found in masses at the centre of each 
 mesh. They were often formed by granular protoplasm with poorly 
 marked limits. The nucleus stained well. These lesions, although 
 diffuse and encountered in all parts, did not involve the entire 
 gland; on the contrary, certain portions remained perfectly healthy. 
 
 In a case of diphtheria the same appearance was found, but the 
 lesions were more discrete. 
 
 It is well to remark that the frequency of thyroideal lesions varies 
 considerably according to different infections. In scarlatina the 
 thyroid is almost constantly the seat of profound alterations, while 
 it resists far better in measles. In the case of a woman who died 
 from confluent variola the gland was the seat of very pronounced 
 lesions. It was hypertrophied and highly congested; small paren- 
 chymatous hemorrhages had also occurred. 
 
 Mechanism and Significance of Thyroideal Lesions. Torry 1 
 attributes to the thyroid gland a special destructive power against 
 bacteria. This action, if real, cannot be considerable. The injec- 
 tions made through the carotid vessels are at least as effective as 
 intravenous. On the other hand, rabbits subjected to thyroid- 
 ectomy resist at least as well as normal rabbits. Moreover, under 
 the influence of infections the thyroid is not spared; it presents 
 the same alterations as the other parenchymatous structures. The 
 reason the lesions in the thyroid are generally less pronounced than 
 those in the liver and kidney is that the activity of the thyroid is 
 slow in the adult. The first effect of infection is to arouse the torpid 
 secretory activity ; for profounder changes to be effected the action 
 of the toxic product must be intense or long continued. 
 
 1 Torry. La tiroide nei morbi infettivi. II policlinico, March 15, April 15, and 
 May 15, 1900. 
 
INFLUENCE OF INFECTIONS UPOJS THE 0RQANI8M. 
 
 In this connection experiment demon trate thai chronic ii 
 < ions give rise in mosl cases to interstitial le ion ; inter e infections, 
 even when of shori duration, produce chiefly cellular alterations. 
 II. may, therefore, be concluded thai the extenl and depth of le 
 depend rather upon the energy than upon the persistence of the 
 morbid processes. This l;iw of general pathology is clearly demon- 
 strated by experimental facts obtained by us. By injection of 
 microbes into the thyroideal arteries we have been able to produce 
 nil degrees of visceral inflammation. By varying the dose or the 
 virulence of cult urcs one may obtain thyroiditis with interstitial 
 predominance— /. e., hemorrhagic thyroiditis, thyroiditis with active 
 leucocytic reaction :ind sclerosis, or thyroiditis with parenchymatous 
 predominance, namely, acute necrosis and degeneration of the cells, 
 or even epithelial proliferation terminating in neoplastic develop- 
 ment. 
 
 These experimental data arc interesl ing, since the same anatomico- 
 pathological types may occur in man. Suppurative thyroiditis, 
 which has long been noted, is to-day well known: it develops in 
 the decline of various infectious diseases. Bemorrhagic thyroiditis 
 is rare; it has been observed in variola by Liouville and ourselves. 
 The other forms may be encountered in acute infection-, though 
 they never present the intensity observed in experimental inflam- 
 mations. Thyroideal sclerosis is rather an incident of chronic dis- 
 eases, such as tuberculosis. It may, however, appear in the course 
 of the most varied infections when these are more or less prolonged. 
 
 How are the various parenchymatous modifications of the thyroid 
 to be interpreted? Experimental pathology enables us to answer 
 this question. If the infected thyroid lie compared to glands the 
 activity of which is excited by pilocarpine or iodine, the phenomena 
 are found to be practically the same. Infection arouses the gland- 
 ular activity, which is expressed by increased secretion. This is the 
 first degree. "When the process is more intense the colloid matter 
 suffers qualitative modifications. Unlike what occurs in animals 
 treated with pilocarpine or iodine, it undergoes a granular trans- 
 formation and loses its normal staining capacity. Thus in the course 
 of infectious diseases more or less marked secretory disorders in the 
 thyroid, as in other glands of the economy, occur. After a period 
 of overactivity a diminution or an alteration oi functions appears. 
 As the liver then secretes abnormal pigments, so the thyroid forms 
 an atypical and peculiar colloid substance. 
 
400 IXFECTIOUS DISEASES. 
 
 Although in the majority of cases the thyroideal lesions are slight 
 and admit of sufficient reparation to permit the re-establishment 
 of its functions, it is clear that such may not always be the case. 
 Alterations may subsist which, at the end of a variable period of 
 time, perhaps several years, having evolved on their own account, 
 may be expressed by functional disturbances; for instance, myx- 
 edema and exophthalmic goitre may be connected with some 
 previous infection. 
 
 The Suprarenal Capsules in Infectious Diseases. 
 
 The suprarenal capsules may be altered in the course of the most 
 varied infections. 
 
 Capsular alterations are very frequent in syphilis (Virchow, Lan- 
 cereaux, Chvostek) and especially in hereditary syphilis. Virchow 
 and Huber noted fatty degeneration in them. Boerensprung, Ollivier 
 and Ranvier described sclerosis of the capsules. 
 
 Since the classical memoir of Addison, tuberculosis of the 
 suprarenal capsules has been described a great many times. 
 There may also be cited cases in which the capsular lesions seem 
 to have played the principal role in the genesis of morbid phe- 
 nomena. In two patients who had rapidly died with typhoid 
 symptoms Virchow found a hemorrhagic inflammation in the supra- 
 renal capsules. 
 
 These facts indicate the interest attaching to the systematic study 
 of the suprarenal capsules in infections. In their memoir on diph- 
 theria Roux and Yersin state that the suprarenal capsules are 
 intensely congested in guinea-pigs which had received living or ster- 
 ilized cultures of Loeffler's bacillus. Charrin and Langlois made anal- 
 ogous statements regarding guinea-pigs inoculated with pyocyaneus 
 virus and noted the presence of small, pigmentary granulations in 
 the interior of the cells. In guinea-pigs which died twenty-four hours 
 after inoculation with Friedlaender's bacillus the author found 1 the 
 suprarenal capsules enlarged; instead of the fine yellow color they 
 presented a dark, ecchymotic hue. In some instances they appear 
 totally invaded by hemorrhages. On section the parenchyma ap- 
 pears transformed simply into a bloody mass; at the periphery of 
 the organ only some intact parts are at times encountered. 
 
 1 Roger. Les lesions des capsules surrenales dans les maladies infectieuses. La presse 
 m<jdicale, February 3, 1894. 
 
INFLUENCE OF INFECTIONS UPON THE ORGANISM. |0| 
 
 Oppenheim and Loper studied 1 the uprarenal cap ule ol fifty- 
 three men who had died from the mo I varied infection . ! 
 constantly found lesions, dilatation of the capillaries, diffuse or cir- 
 cumscribed hemorrhages, venous thromboses, cellular necroses, and, 
 here ;iikI there, masses of polynuclears. These are substantially the 
 same modifications as those observed in animal , 
 
 Considering the various results obtained and the frequenl occur- 
 rence of sclerosis as a result of infectious lesions, we are led to the 
 assumption thai after an acute disease the suprarenal capsules often 
 remain altered inapermanenl manner; therefore, various disorders 
 due to their incompetency may later be observed. A- a matter of 
 fact, since the clinical investigations of Sergenl and Bernard we 
 know that there is a syndrome different from Addison's disease, and 
 characteristic of capsular insufficiency. In most cases the symptoms 
 arc connected with tuberculosis and follow an acute or subacute 
 course, at times rapidly terminating in death. < )f special importance 
 for our subject is the fact that these phenomena a1 times develop 
 on the occasion of even a slighl infection, such as a pultaceous 
 angina, as was the case observed by Sergent and Bernard. 2 
 
 1 Oppenheimer and Loper. Lesions des capsules Burrenales dans quelques maladi>- 
 infectieuses aigii-s. Socictc de biologic, July 13, 1901. 
 
 7 Sergent and Bernard. Sur un syndrome clinique non addisonien lie 1 a 1 'insuffi.sance 
 capsulaire. Archives generales de ni(5decine, July, 1899. 
 
 26 
 
CHAPTER XIV. 
 
 INFLUENCE OF INFECTION UPON VARIOUS PARTS OF 
 THE ORGANISM {Continued). 
 
 Disturbances and Alterations of the Nervous System. Cerebral Manifestations. Ceph- 
 alalgia. Delirium. Relationship between Delirium and Lesions of the Liver and 
 Kidney. Post-infectious Delirium. Tubercular Insanity. Obnubilation and Coma. 
 Aphasia. Hemiplegia. Convulsions. Bulbar Manifestations. The Spinal Cord in 
 Infections. Hydrophobia. Tetanus. Infectious Myelitis in Man. Acute Ascend- 
 ing Paralysis. Infantile Paralysis. Myelites in Various Infections. Diphtheritic 
 Paralyses. Post-infectious Neuroses. Infectious Meningites. Cutaneous Manifes- 
 tations of Infections. Exanthemata in the Eruptive Fevers. Mechanism and 
 Variability of Infectious Erythemata. Relationship Between the Intensity of 
 Eruption and Gravity of the Disease. Sudoral Secretion in Infections. Evolu- 
 tion of Exanthemata. The Muscular System in Infections. Infectious Osteop- 
 athies and Arthropathies. 
 
 The Nervous System in Infections. 
 
 All infectious diseases are capable of involving the nervous 
 system; a few affect it in an exclusive or predominant manner. 
 
 For the convenience of description we may admit the following 
 di visions : 
 
 1. Reactionary disturbances of the nervous system in the course 
 of infections. 
 
 2. Non-specific lesions of the nervous system. 
 
 3. Awakening or appearance of nervous affections. 
 
 4. Specific lesions, viz., secondary localization of the infectious 
 process. 
 
 5. Primary infection of the nervous system. 
 
 Nervous disturbances are observed in almost all diseases : fatigue, 
 exhaustion, headache, delirium, convulsions, twitching of the tendons, 
 and modifications in the activity of certain organs or systems are 
 manifestations of frequent occurrence. They appear at a variable 
 epoch of the evolution, subside with it, or persist after apparent cure 
 of the disease. They may dominate the morbid tableau by reason 
 of their intensity, thus leading to the development of particular 
 clinical forms, such as ataxic, ataxo-adynamic, convulsive, delirious, 
 and comatose. 
 
INFLUENCE OF INFECTIONS UPON THE ORGANISM. 403 
 
 The explanation of these disturbance) i to I"' found, il seem in 
 intoxication. 
 
 It, is, therefore, conceivable thai causes favoring or aggravating 
 the* formation mid relent ion of toxic substances play an important 
 role in (lie production of the nervous phenomena. The lesions of the 
 organs concerned in the transformation or elimination of the poisons, 
 notably I'll" liver, kidneys, and lungs, play an additional rdle, as do 
 likewise the various conditions favorable to the production of toxins, 
 the virulence of Hie microbe, rapid dii b isimilation, and hyperpyrexia. 
 Thus, deliriuni niiiy :i.p|)e:ir in consequence of lesions of an apparatus 
 which until Mien was intact, for instance, the kidneys or lunj 
 
 These ordinary reactions have a common basis. Although they are 
 identical in all diseases, they al times presenl peculiar characters due 
 to the action of specific products secreted by microbes and, more 
 particularly, to the inherited or acquired predisposition of the sub- 
 ject. 
 
 It may be stated that, in a great number of cases, morbid 
 manifestations represent functional reactions and simply expr 
 disturbance of the nervous system; it is conceivable, however, that 
 the prolongation or repetition of the derangement may result, more 
 or less rapidly, in anatomical alterations. It is very difficult to say 
 at what moment the functional disturbance gives way to anatomical 
 lesion. It may even be doubted whether the distinction is well 
 founded. In cells which no longer discharge their functions in a 
 normal manner the protoplasm must certainly undergo alteration-, 
 although these changes are not appreciable until they become suf- 
 ficiently well pronounced. 
 
 When the nervous affection becomes apparent during the course 
 or at the end of the disease, the etiology is evident, but when months 
 or years elapse between recovery from the first disease and the 
 appearance of nervous phenomena, the problem then becomes highly 
 complex; hence the origin and connection of the nervous symptoms 
 have long been a matter of delicate discussion. 
 
 At the present day there can no longer be any doubt, since experi- 
 mental pathology has succeeded in producing in animals a series of 
 nervous affections, and notably myelitis, by means of inoculations 
 with more or less virulent germs. Accurate clinical observation has 
 finally removed the last shadow of doubt. It may now be affirmed 
 that all nervous affections, save family and hereditary diseases, are 
 caused by some infection or intoxication. The best differentiated 
 
404 IXFECTIO US DISEASES. 
 
 clinical types may follow the most varied infections. In the presence 
 of this new pathogenic view we must not, however, lose sight of the 
 role of predisposition, which alone enables us to explain the localiza- 
 tions of the process. 
 
 Infection may also provoke the appearance, aggravation, or return 
 of latent, slight, or past manifestations. It is known that infection 
 often acts as a provocative agent for certain neuropathies, particu- 
 larly hysteria. 
 
 After the reactionary phenomena we may mention the secondary 
 localizations of infectious processes. It suffices to cite, for instance, 
 tubercles, abscesses, and gummata of the nerve centres and their 
 envelopes. These lesions acquire no particular character from their 
 localization. Pathogenic agents colonize in the nerve centres as 
 they do in other parts of the organism, and there give rise to reactions. 
 
 Instead of being secondary, an infectious localization is at times 
 primary. The pathogenic agent attacks the nervous system from 
 the beginning. It may be propagated into the nerve centres or, 
 having vegetated at some other point of the economy, secrete soluble 
 substances which reach and become fixed in the nerve centres. As 
 illustrations we may cite hydrophobia and tetanus. 
 
 These distinctions are of great theoretical importance. In prac- 
 tice, however, it is often difficult to determine the mechanism set in 
 motion. It is therefore necessary, for the description of facts, to 
 consider them from the clinical standpoint and simply pass in review 
 the manifestations which may occur in the various parts of the 
 nervous system, namely, the brain, the medulla oblongata, the spinal 
 cord, and the peripheral nerves. 
 
 Cerebral Manifestations. The influence of infectious diseases upon 
 the brain may be expressed by two orders of phenomena: (1) diffuse 
 manifestations, such as headache, incapacity for work, cerebral 
 obnubilation, delirium, and convulsions; (2) symptoms indicating 
 focal lesions, such as aphasia and hemiplegia. 
 
 The necropsy sometimes reveals a focus of softening due to an 
 embolus or thrombus; at other times, acute encephalitis, a cerebral 
 abscess, a meningitis, or a thrombosis in the sinuses. Such marked 
 lesions are seldom met with. In the great majority of cases there 
 is found simply a congestion and, at times, slight hemorrhage. In 
 some instances a slight serous effusion is detected in the meshes of 
 the pia mater and in the ventricles. Lesions of this kind are encoun- 
 tered, especially in typhoid fever. In this disease more profound 
 
INFLUENCE OF INFECTIONS UPON THE ORGANISM, \>,:, 
 
 alterations are sometimes me1 with, uch a arteritis, menii 
 hemorrhages, and cerebral absce i 
 
 A last group comprises tho e cases in which the necropsy if nega- 
 tive: the brain appears healthy. In uch case the cerebral symp- 
 toms have been attributed to circulatory disorders, pyrexia, and 
 mierobic localizations. Ii is now known thai the question is one of 
 intoxication of ili< i organism by tnicrobic products and by waste ol 
 cellular nutrition. Ii is, therefore, perfectly intelligible thai results 
 should greatly vary according to the nature, intensity, or duration 
 of (lie infectious process. 
 
 Cephalalgia. Cephalalgia is observed in all febrile processes; it 
 assumes a certain importance in several diseases. It is particularly 
 interesting to study headache in typhoid fever. It often constitutes 
 the first symptom of ihe disease. A pcrsistonl headache accom- 
 panied by some gastric disturbances, ocfurrin.tr in a young person 
 who has been a short time in a greal city, should immediately sugg 
 typhoid fever. During the stationary stage headache persists; it is 
 generally very severe, and the patient refers his insomnia to it. In 
 cases of moderate intensity, headache lasts to the end of the evolu- 
 tion; in graver cases it disappears, overcome by the stupor which 
 invades the patient. When the question is one of those slight forms 
 designated as "walking typhoid cases" headache is often the only 
 symptom, and thus acquires great diagnostic value. 
 
 Cephalalgia is less marked in the eruptive fevers. Measli - is 
 attended by hardly any headache, and the slight pain seems to be 
 referable to the coryza. It is more intense in variola and scarlet 
 fever, but generally ceases with the appearance of the eruption. The 
 return of headache during convalescence is often the first sign of a 
 renal complication. 
 
 We must also note the importance of headache in various forms 
 of malaria. It is often one of the first morbid phenomena. Its 
 appearance in a man who has just passed through a swampy country 
 should immediately suggest malarial infection. It is one of the best 
 premonitory symptoms. It is also one of the first symptoms of the 
 intermittent paroxysm; cephalalgia precedes the chills, persists 
 during the cold stage, and diminishes during the stage of heat. When 
 it occurs in the intervals of paroxysms the development of a per- 
 nicious character is to be feared. Finally, after cure of the febrile 
 paroxysms, headache may recur in a regular manner: it then repre- 
 sents a form of masked malaria which is not rare in Europe. 
 
406 INFECTIO US DISEASES. 
 
 At times headache indicates a cerebral complication ; it may mean 
 involvement of the meninges, especially in those cases in which a 
 suppurative lesion of the nose or ear exists. It is well to note that, 
 contrary to classical opinion, meningites, even of suppurative type, 
 are often latent, ami give rise to no reaction and, notably, to no pain. 
 
 Besides headache, the patient not infrequently complains of ver- 
 tigo. This symptom is especially marked in influenza and typhoid 
 fever. In the latter disease it is manifested as soon as the patient 
 changes position or sits up in bed. At the beginning of the infection, 
 when the diagnosis is yet doubtful, this phenomenon possesses certain 
 semiological value. 
 
 Delirium. The frequency and clinical appearance of delirium 
 depend upon two factors: the state of the subject and the nature of 
 infection. 
 
 The age of the patient plays a very important role. Children are 
 often subject to delirium, except, of course, in the first years of life, 
 when the cerebral centres are not sufficiently developed for reacting. 
 The newly-born is a medullary being, and the infectious manifesta- 
 tions are the result of the action upon the spinal cord. Delirium is 
 of very frequent occurrence in adults ; it is less frequent in the aged ; 
 the latter are more apt to be attacked by torpor and adynamia. 
 While more common in debilitated or overworked persons, and in 
 women more than in men, delirium is particularly influenced by 
 hereditary or personal antecedents of the patient. Certain individ- 
 uals predisposed by heredity become delirious on the occasion of any 
 febrile process ; it is a mild form, and ceases as soon as the attention 
 of the sufferer is fixed. Acquired predisposition is generally due to 
 previous affections, mainly to intoxications. Alcoholism plays the 
 principal role and gives rise to well-known special disturbances 
 described under the name delirium tremens. This is an event occur- 
 ring in the course of a chronic intoxication and as a result of an 
 abrupt shock. It, therefore, generally appears in diseases character- 
 ized by a sudden onset, such as variola, scarlatina, erysipelas, rheu- 
 matism and, above all, in pneumonia. It is exceptional in those 
 infections which, like typhoid fever, set in slowly, and progressively. 
 
 From a general standpoint, delirium is manifested in three different 
 degrees: 1. Mild delirium, generally bearing upon the habitual occu- 
 pations of the patient and ceases when his attention is called to it. 
 2. Delirium characterized by the muttering of incoherent speech, and 
 often accompanied by sensory hyperesthesia, which explains the hal- 
 
INFLUENCE OF INFECTIONS UPON THE ORGANISM. 407 
 
 Lucinations and illusions of sighl and of hearing. •'». Furiou delirium 
 is one of action: the patienl howls, sings, recognizee nobody, an 
 no questions. Sensibility is diminished. The sufferer is detached 
 from the externa] objective world, and i seized with terrifying hal- 
 lucinations. Willi haggard ;md conge ted eyes and trembling Limbs 
 he leaves Ins bed and inns about the room, fighting those who 
 to arrest or calm him. 
 
 The delirious manifestations of the stationary period generally 
 disappear at the end of i tie disease. In certain instances, howi 
 some trouble of the intellect or memory may persist. In other* 
 more serious phenomena appear. Such, for example, is the condition 
 described by alienists under the name mental confusion. It occurs 
 in the most varied diseases: in typhoid lexer, variola, cholera, influ- 
 enza, pneumonia, and erysipelas. The ideas of the victim are bo 
 confused that he utters only fragments of phrases; his language 
 becomes unintelligible. His perceptions are not clear. His face is 
 weak and stupid. In spite of their apparent gravity, however, 
 these troubles are in most cases transitory, and gradually disap- 
 pear. 
 
 Post-infectious Delirium. Mania may occur in consequence of the 
 most varied infections: typhoid fever, rheumatism, erysipelas, erup- 
 tive fevers, cholera, etc. On consulting a treatise on mental path- 
 ology it will be seen that the most varied clinical types of mental 
 diseases may occur as a result of an infection. The same dia 
 are mentioned in the etiology of manias, mental degenerations, 
 various forms of insanity, and even of general paralysis. Their rela- 
 tive frequency is not exactly the same. Thus, mental degenerations, 
 accompanied or unattended by bodily degenerations, are the inflic- 
 tions of hereditary syphilis: they are also observed after typhoid 
 fever, but are exceptional after other infections, such as the eruptive 
 fevers, diphtheria, mumps, and whooping-cough. In the etiology of 
 general paralysis (aside from the influence of syphilis, which Mill be 
 referred to later) are cited typhoid fever, influenza, pneumonia, diph- 
 theria, variola, and especially erysipelas. 
 
 Tubercular Insanity. Although insanity is at times consecutive 
 to a transitory disease, it may also occur in the course of a chronic 
 infection, such as syphilis or tuberculosis. The relationship between 
 insanity and phthisis has been repeatedly studied. Alienists have 
 long noted the frequent coincidence of the two processes, the fre- 
 quency of tuberculosis among the ancestors of the insane, and at 
 
408 INFECTIOUS DISEASES. 
 
 times the alternation of thoracic symptoms and of cerebral disorders 
 in the same individual. 
 
 The mental state of the tubercular is often very peculiar. Their 
 optimism and indifference is a matter of common observation. Some 
 of them recognize their state and accept it with resignation. How 
 different is this from the alarm into which most people are thrown 
 on the slightest morbid manifestation. Certain tubercular subjects, 
 however, are of a different temper; they always complain, and 
 nothing satisfies them. Others become suspicious, and may believe 
 themselves to be objects of persecution. 
 
 Finally, at the terminal period, intellectual derangements appear, 
 as a rule. They occur tardily, however; a violent delirium with hal- 
 lucination is a symptom of approaching death. 
 
 In certain cases a paroxysm of true insanity may occur in the course 
 of ordinary tuberculosis. We had the opportunity to observe a case 
 of this kind in which very marked disorders evolved in successive 
 periods, characterized by alternating manifestations of depression 
 and excitation. 
 
 Role of Infections in the Development of General Paralysis. 
 Among the maladies of infectious origin, general paralysis deserves 
 first mention. It follows typhoid fever, pneumonia, diphtheria, 
 variola, and, as has been shown by Bayle and Baillarger, especially 
 erysipelas. The influence of syphilis seems also to be undeniable. 
 Sj^hilitic general pseudoparalysis, however, must be distinguished 
 from true general paralysis. The former is connected with diffuse 
 syphilitic lesions and is remarkable for the existence of certain 
 peculiar symptoms — i. e., ptosis, strabismus, local paralyses, and 
 cephalalgia. Delirium is slight and often assumes the circular form. 
 Finally, its course is different; it is often regressive, and a cure may 
 be effected by specific treatment. Aside from this somewhat peculiar 
 clinical type it must be recognized that syphilis is too frequently 
 found in the antecedents of general paralytics to be simply an acci- 
 dental coincidence. Syphilis does not, however, produce general 
 paralysis ; it fulfils here the same role as in the development of loco- 
 motor ataxia: it is an auxiliary cause acting upon predisposed 
 individuals. 
 
 Obnubilation and Coma. Infections often give rise to an obnu- 
 bilation sufficiently pronounced to border on coma. It is a nervous 
 depression supervening at once or following phenomena of excitation, 
 notably delirium. 
 
INFLUENCE OF INFECTIONS UPON THE ORGANISM. KM) 
 
 Cerebral obnubilation is very marked in typhoid fever, typhus, 
 and pneumonia in the aged. If al o characterise one of the forme 
 of pernicious malarial fever. In the cour e of the eruptive fevers il 
 presents a certain diagnostic value according to the date of ito appear- 
 ance. At the beginning of scarlatina and mea le a semicomatose 
 state is not a symptom of extreme gravity, al leasl in children. It. 
 however, it does not subside a1 the time of eruption the prognosis 
 becomes grave. 
 
 The appearance of coma during convalescence indicates a compli- 
 cation and particularly a bronchopneumonia in a case of measles, 
 and a nephritis in a ease of scarlatina. 
 
 These comatose manifestations are a1 all events rare. With their 
 study we have completed the consideration of diffuse cerebral mani- 
 festations. We shall now review certain phenomena which seem to 
 indicate a more precise localization. 
 
 Aphasia. Aphasia may occur unassociated with hemiplegia. It 
 appears during convalescence from the eruptive fever-, erysipelas, 
 and particularly typhoid fever. It is mosl frequently observed in 
 children. At any rate, the trouble is incomplete and transitory, and 
 recovery is effected in two or three weeks. Leyden attributes it to 
 a focus of slight encephalitis. Certain cases mighl perhaps be ex- 
 plained by neurotic disorders, as we are led to believe by observation 
 of a case of measles in a girl, three years of age, who, two days after 
 the fall of the fever, had frequent fits of hysteria, and at the same 
 time lost the use of language, save two words, "Boni, madame," 
 which was her invariable reply to all questions. This aphasia lasted 
 fifteen days and then gradually disappeared. 
 
 We must not overlook aphasia occurring in malaria. In some ci - - 
 the disturbance of speech appears after a regular paroxysm: it is 
 transitory and not serious. At times it manifests itself in a per- 
 nicious paroxysm and is of grave prognostic significance. 
 
 Hemiplegia. Hemiplegia may be produced by various mechan- 
 isms. It may be due to emboli derived from a clot of phlebitis 
 vegetations of an ulcerative endocarditis. In the latter instance the 
 symptom acquires a certain diagnostic value. "When the diagnosis 
 is doubtful as to the nature of infection observed — when, for example, 
 typhoid fever is thought of — the sudden appearance of hemiplegia 
 will lead to a more careful examination of the heart, and thus enable 
 the physician to recognize 1 the nature of the events. 
 
 Hemiplegia dependent upon a focus of cerebral arteritis is an 
 
410 INFECTIOUS DISEASES. 
 
 incident of rare occurrence. "We have observed a case of this kind, 
 that of a man, thirty-three years of age, who, consecutively to a 
 gastroenteritis, developed a right hemiplegia involving the limbs 
 and the. face, but sparing the orbicularis palpebra?. The necropsy 
 revealed an acute arteritis in the arch of the aorta and red softening 
 occupying the middle of the ascending convolutions on each side of 
 Rolando's fissure, affecting quite deeply the cortical part. 
 
 Hemiplegia is not extremely rare in pneumonia, at least in the 
 aged. It sets in after an apoplectic attack and is often attended by 
 conjugate deviation of the head and the eyes. Death occurs within 
 a few days in coma. At the necropsy cerebral softening is discov- 
 ered. According to Straus, this lesion is constant, but so small as to 
 easily escape notice. 
 
 There are also transitory hemiplegias observed, particularly during 
 convalescence from infections, but they are extremely rare. 
 
 Convulsions. As infantile poliencephalitis is less frequent than 
 poliomyelitis, owing to the fact that in children the brain is less 
 active than the spinal cord, the same is true of delirium which, in 
 children, is replaced by convulsions, especially in those predis- 
 posed by heredity or innateness. When they occur at the beginning 
 of infections they are not of grave diagnostic significance. They 
 often accompany the invasion of an eruptive fever, angina, and 
 notably pneumonia. In the last-named disease convulsions are 
 observed chiefly in children under two years of age, thus justifying 
 the assumption of an eclamptic form. 
 
 Tardy convulsions, unlike early ones, frequently announce the 
 development of some complication. In measles they must suggest 
 bronchopneumonia; during convalescence from scarlatina they gen- 
 erally constitute the first symptom of nephritis. In other instances 
 they express some lesion of the nervous centres, and are, for example, 
 related to the development of meningitis. If convulsions occur in 
 the course of a whooping-cough, without aggravation in the general 
 state of the patient and without production of fever, they are to be 
 attributed to an exaggeration of the nervous reactions induced by 
 the disease : the local convulsion is generalized. On the other hand, 
 if at the same time there is persistent dyspnea and a rise in tem- 
 perature, the patient must be examined with greater care, and almost 
 always bronchopneumonia will be discovered. 
 
 Finally, as the majority of adults succumb in delirium, so most 
 children under two years of age die during terminal convulsions. 
 
influence OF INFECTIONS UPON THE ORGANISM. ill 
 
 They behave at I lie cud of infection ■■> they do al Hi'- beginning, 
 presenting nervous reactions which are referable to the jame i 
 as in adults, but :ue localized in differenl parts of the nervous 
 system. 
 
 Convulsions are quite uncommon in adults. Scarlatinal nephritis, 
 which produces convulsive uremia in children, gives rise to dyspneic, 
 delirious, or comatose uremia in adults. Puerperal eclampsia i- an 
 exception to (his rule; si ill, in not :i U-w cases puerperal uremia is 
 expi'essed l>y oilier n i : 1 1 1 i festations, notably by ;i violent delirium 
 which, in the absence of an examination of the mini', would very 
 likely be mistaken For a phenomenon of acute insanity. 
 
 Bulbar Manifestations of Infections. 
 
 The majority of infections affect the bulbar centres. Fevers seem 
 to be dependent upon dynamic modifications produced in the 
 medulla oblongata. Certain phenomena accompanying fever, 
 notably chills, are also referable to a bulbar influence. 
 
 The medulla oblongata also contains centres governing the func- 
 tions of the principal organs. Various cardiac disturbances are of 
 bulbar origin. Acceleration of pulse in fever is no1 simply due to 
 the rise in temperature, for, if such were the case, it would follow 
 nearly the same course in all diseases. The fact is, however, that 
 certain diseases affect far more than others the number of pulsations 
 and are precisely those maladies which most easily excite nervous 
 reactions. In this respect scarlatina is the leading affection. In 
 this disease, for the same degree of temperature, the pulse is far more 
 rapid than in other infections. This is even a valuable diagnostic 
 symptom, since it enables the physician to state, prior to the eruption, 
 that the sore throat is probably of scarlatinal nature. On the other 
 hand, slowness of pulse may express the influence of an infection 
 upon the bulb, and such slowness, coinciding with the thermal ele- 
 vation, becomes a striking feature. In a man. twenty-one years of 
 age, suffering from a serious scarlatina complicated with albuminuria. 
 the number of pulsations fell to 52, although the temperature was 
 102.2° F. (39° C). This state persisted for three .lays. It was prob- 
 ably due to a bulbar disorder, since, under the influence of a small 
 dose of atropine, which diminished the action of the pneumogastric 
 nerves without suppressing it. the pulse-rate rose to 64. 
 
 We likewise attribute to disturbances of cardiac and respiratory 
 centres the arrhythmias, the irregularities of the heart's action, which 
 
412 IXFECTIO US DISEASES. 
 
 occur without the slightest demonstrable lesion in the myocardium. 
 A similar explanation must be admitted with reference to certain 
 paroxysms of dyspnea, acceleration or retardation in respiratory 
 movements, which are accounted for neither by fever nor the state 
 of the heart, kidneys, or lungs. 
 
 The Spinal Cord in Infections. 
 
 The participation of the spinal cord in infectious processes is 
 demonstrated beyond dispute by the study of two diseases: one 
 caused by multiplication of the pathogenic agent, the other by the 
 action of microbic toxin — we refer to hydrophobia and tetanus. In 
 hydrophobia the pathogenic agent acts by means of the products 
 which it secretes. When, after having been freed from all figurate 
 elements, an emulsion of the spinal cord of hydrophobic animals is 
 injected into dogs, paralytic phenomena are produced. It is an 
 intoxication, not an infection, since the cord of these inoculated dogs 
 is not virulent. 
 
 This toxin is produced in the various parts of the nerve centres, 
 and these are invaded successively, not simultaneously. The patho- 
 genic agent slowly propagates and colonizes. The experiments of 
 Di Yestea and Zagari show that the introduction of the virus into 
 the sciatic nerve causes a more marked paralysis on the side into 
 which the inoculation is made, and that the tail of the horse becomes 
 virulent before the medulla oblongata. Clinical observation is in 
 harmony with these experimental facts ; it shows that convulsive or 
 paralytic phenomena are often more pronounced on the bitten side. 
 According to the remark of the authors above mentioned, a bite in 
 the lower extremities commonly gives rise to paraplegia, while the 
 rabid forms usually occur when the initial lesion is inflicted on the 
 head or upper extremities. 
 
 Of the two clinical forms of hydrophobia, one, the rabid form, is 
 in fact characterized by the predominance of cerebral manifestations ; 
 the other, the dumb or paralytic type, by the prevalence of spinal 
 phenomena. These two forms may be encountered in all animals, but 
 their relative frequency varies from one species to another. The 
 rabid form is more frequent in the dog, while in the rabbit the disease 
 almost constantly assumes the paralytic form. 
 
 Anatomical pathology shows, on the other hand, that the lumbar 
 spine is affected if the person is bitten in the lower extremities; if 
 the wound is received in the upper extremities the cervical spine is 
 
INFLUENCE OF INFECTIONS i r<>\ THE ORGANISM. |]:; 
 
 found to be the seal of alteration! . the e alteration* consisting nol 
 in mere congestion, bu1 in tnall foci of Boftening. Microscopic or 
 even larger hemorrhages resulting from the rupture of congested cap- 
 illaries as well as thrombosis are le ion of frequent occurrence. The 
 in 'I've cells are altered jal some points they are destroyed and replaced 
 by masses of embryonal elements or neuroglia tissue. 
 
 In view of the results furnished by experimentation and clinical 
 observation we may state, in conclusion, thai the agent of hydro- 
 phobia is essentially a parasite of I he QervoiM system, the peripheral 
 prolongations of which it follows in order to reach and localize itself 
 in the nerve centres and there produce its toxin. Accordh 
 the ancient expression of Romberg, hydrophobia may therefore be 
 said to he a toxoneurosis; we must only add: an infectious and 
 specific toxoneui'osis. 
 
 Tetanus. The second infectious t < >xoneurosis known i- tetanus. 
 It essentially differs from the preceding infection in that the patho- 
 genic agent remains localized at the point of introduction and secretes 
 toxins which follow the nerves in order to reach the spinal cord, the 
 bulb, and the brain. Its mode of action ha- been and is -till a 
 matter of discussion. Courmont and Doyon believe its action to he 
 that of a ferment which gives rise to a new poison of a convulsifying 
 character. Others, following Ehrlich, admit a combination of the 
 toxin with the protoplasm of the nerve cells, an intracellular trans- 
 formation thus being effected. 
 
 It remains to determine what part of the nervous system is the 
 starting point of the disorders. Pathological anatomy having 
 afforded no conclusive results, physiological analysis must be resorted 
 to. At present there is general agreement for localizing the disorder 
 in the cord and the medulla oblongata : and, following Courmont and 
 Doyon, 1 it is admitted that the process is one of exaggerated sensi- 
 tiveness of the reflex axis, the poison acting probably upon the 
 sensory neuron. This conclusion is in perfect harmony with the 
 results of experiments made by the author as regards the sensitive- 
 ness of tetanic animals to the action of strychnine. 2 
 
 Guinea-pigs, from two to seven days after inoculation with tetanic 
 toxin, received beneath the skin small doses (from 0.5 to 1 mg 
 strychnine sulphate. They presented convulsions and. in most 
 
 1 Courmont and Doyon. Le tetano*. Actualites medicates. 1899, vol. i. 
 : Roger. Action de la strychnine et du chloral sur le< animaux tetanique*. Soc. de 
 biologic. May 20. 1899. 
 
414 INFECTIOUS DISEASES. 
 
 cases, soon succumbed. Control guinea-pigs withstood the same 
 amounts of the alkaloid without presenting the slightest disturbance. 
 
 Infectious Myelites in Man. Numerous facts of comparative and 
 experimental pathology demonstrate the frequency of paralyses of 
 spinal origin consecutive to infections. In clinical experience it is 
 often difficult to determine a localization. The symptoms may 
 depend upon very different processes. Three diseases or rather three 
 clinical types may be referred to infection. These are the acute 
 ascending paralysis, infantile paralysis, and acute spinal paralysis 
 of the adult. Their history will complete the teachings already fur- 
 nished by the study of hydrophobia and will enable us to better 
 appreciate the complex facts to be later described. 
 
 Acute Ascending" Paralysis. Acute ascending paralysis or Lan- 
 dry's disease may occur in typhoid fever (Landry, Leudet, Pitres, 
 and Vaillard), pneumonia (Gubler and Landry, Macario), measles 
 (Barlow, Negue), variola (Gubler, Bernhardt, Gross, Chalvet, Oettin- 
 ger, and Marinesco), in consequence of puerperal septicemia (Landry) 
 or urinal septicemia (Orcel and Stourine, Prince), and consecutive 
 to suppurative wounds produced by a vesicatory (Landry, Gubler). 
 In some cases the invasion is announced by certain disturbances 
 attributed to influenza or an attack of indigestion. In other instances 
 the onset is characterized by general manifestations, malaise, loss of 
 appetite, chills, and especially fever. Finally, as in all microbic 
 processes, the intervention of some auxiliary cause is often noted in 
 the beginning of the disease, such as indigestion, cold, overexertion, 
 and excesses, which favor the development and localization of the 
 germs. 
 
 Some of the symptoms of the stationary period indicate the infec- 
 tious nature of the malady. First of all, fever which, it must be 
 acknowledged, is not constant; also malaise, anorexia, and, not infre- 
 quently, hypertrophy of the spleen. What further strengthens the 
 conviction that acute ascending paralysis must be of infectious origin 
 is the fact that there is an infection of the nervous centres which, by 
 its symptoms and evolution, strongly resembles Landry's paralysis 
 — reference is here made to paralytic hydrophobia. The perusal of 
 certain observations leads to the question whether some cases 
 recorded as examples of Landry's paralysis are not due to the virus 
 of hydrophobia. Leaving aside this doubtful question, it is noticed 
 that the evolutive analogy leads to the assumption of a pathogenic 
 analogy and, therefore, to a search for an animate agent in Landry's 
 
INFLUENCE OF INFECTIONS UPON THE ORGANISM. \ \ :, 
 
 disease. Researches in this direction have already been pm 
 wi ih some success. Baumgarten found in the blood and organ* a 
 bacillus resembling thai of anthrax. Marie and Afarinesco obtained 
 a similar resull . ( tentanni saw numerou tnicrobe ranged in a semi- 
 lunar form around the fibres of peripheral nerves, none being encoun- 
 tered in the cord. Ii is impossible, however, to express a decided 
 opinion willi regard to these various findings, since none of the 
 going authors completed his investigations by cultivation and inocu- 
 lations. 
 
 In a case of Curschmann the symptoms made their appearance in 
 the course of a typhoid fever and were ascribed to Eberth's bacillus, 
 which was, in fact, found in the while substance of the spinal cord. 
 The nature of the microbe was determined by cultivation and inocu- 
 lation. In other instances common or at leasl non-specific bacteria 
 have been encountered. The staphylococcus aureus was found twice 
 by Eisenlohr, the streptococcus in the case of ( tettinger and Marin- 
 esco, which coccus was cultivated in the case of Remlinger. Lastly, 
 in a case in which microscopic examination had failed to disclose the 
 presence of any germs, Thomas obtained a culture of a micrococcus 
 liquefying gelatin. 
 
 Thus in nine cases which have been more or less carefully studied 
 from a bacteriological standpoint there was found twice a bacillus 
 resembling that of anthrax, twice undetermined microbes, once 
 Eberth's bacillus, twice the staphylococcus aureus, and twice the 
 streptococcus. In two other cases, one observed by Eisenlohr, the 
 other by Albu, the research for bacteria was negative. 
 
 From these somewhat dissimilar facts no definite conclusion can 
 be derived. It can only be stated that the majority of modern 
 observations lead to the assumption that Landry's disease is an acute 
 poliomyelitis which may be produced by the most varied microbes. 
 
 The following observation 1 tends to support this view: A man, 
 thirty-three years of age. ten days before his admission to our hos- 
 pital experienced sensations of intense cold in the lower extremities, 
 and, three days later, numbness in the legs, but no pain at any time. 
 The lower extremities became progressively weaker, and he was com- 
 pelled to lie in bed; then throat symptoms appeared, upon which he 
 was sent to the hospital. He suffered a violent paroxysm of dyspnea 
 on taking a glass of milk. His intellect was intact. Perspired pro- 
 
 1 Roger and Josue\ Un cas de paralysde ascendants aigue. La Presse mexiicale. 
 July 27. 1898. 
 
416 ISFECTIO US DISEASES. 
 
 fusely. He was hoarse, but nothing abnormal was found in the 
 throat. Every time he drank, however, he had a paroxysm of suffo- 
 cation. Paralysis of the lower extremities was complete; the upper 
 extremities were only weakened. There was also slight aiursthesia, 
 which was more marked in the lower than in the upper extremities. 
 The patellar reflexes were abolished as well as the tendon reflexes of 
 the upper extremities. Pulse 112; temperature 101.6° F. (38.7° C.) 
 in the morning, 100° F. (37.8° C.) in the evening. On auscultation 
 sibilant and sonorous rales were heard. He died in the night during 
 an attack of dyspnea. The histological examination of sections of 
 the lumbar enlargement showed lesions in the cells of the anterior 
 horns, remarkable alike for their degree, amounting to an atrophy of 
 the nervous elements, and for their diffusion: nearly all the cells were 
 altered. On bacteriological examination no microbic foci were found. 
 We therefore resorted to cultivation and inoculation in order to 
 determine the cause of the disease. 
 
 With a sample of the blood which was taken from the right heart 
 immediately after death we obtained cultures of a microbe presenting 
 all the characters of the pneumococcus. With these cultures we 
 made inoculations into animals. Rabbits presented paresis or spas- 
 modic paralysis in the hind legs. Their blood, cultivated in various 
 media, yielded pure cultures of the pneumococcus. 
 
 Our observation is the first to establish the existence of an acute 
 ascending paralysis produced by the pneumococcus. This result is 
 not to be wondered at. There are cases on record showing that pneu- 
 monia may be followed by an ascending paralysis. Landry's famous 
 observation is an illustration thereof : the patient had had an attack 
 of pneumonia from which he had not completely recovered. He 
 remained in that condition for two months, and then developed 
 paralysis, which killed him in a week. It may, of course, be objected 
 that, in this case, the lapse of a long period of time between the 
 thoracic and spinal manifestations renders impossible the unreserved 
 admission of a relationship of cause and effect. 
 
 No such objections can be raised against our case, which demon- 
 strates the possibility of an ascending paralysis of pneumococcic 
 origin. It is true that in our case the nature of the infection could 
 not be determined without the assistance of bacteriology. The lungs 
 did not present the lesions which the pneumococcus usually produces 
 therein. It is well known to-day, however, that the pneumococcus 
 is capable of giving rise to various infections without pulmonary 
 
INFLUENCE OF INFECTIONS UPON THE ORGANISM. 117 
 
 alterations. Numerous facts have been related to show thai this 
 mierobe frequently reaches the nervous centre . I' i nol trange, 
 therefore, that it r m .1 \- also produce spinal localization , 
 The pneumococcus isolated by us poi ei ed the property of pro 
 
 (hieing in ;i.nini:ils, ;is it h:ul done in man, nerVOU manife- ta1 
 
 Three of our rabbits developed paraplegia under its influence. M 
 seems, therefore, thai after il had once given rise to spinal disorders 
 the microbe had acquired a sorl of elective harmfulnesf for the 
 
 nervous system. A si udy of i his facl led ii- i" the view thai microbes 
 may become accustomed to a residence in certain parte of the organ- 
 ism, nnd thus always manifest ;i tendency to localize themselves in 
 the same tissue in ;i predominant or exclusive manner (p. I'd . 
 
 Infantile Paralysis. The infectious nature of infantile paralysis is 
 established upon a fairly large number of clinical proof-. The spinal 
 symptoms have at limes developed consecutively to a well-deter- 
 mined infection; at oilier limes i hey have been observed simulta- 
 neously in a number of children, and prevailed in an epidemic form 
 (observations of Cordier, Leegaard, Medin, Briegleb, Cerversato, 
 Auerback, Zapped ). These epidemics are commonly observed during 
 summer, and often coexist with epidemics of polioencephalitis. The 
 symptoms develop at once or in consequence of some infection, such 
 as measles, scarlatina, or erysipelas. It is not an easy matter to say 
 whether acute myelites should be related to cerebrospinal meningitis 
 and considered as due to a specific microbe, or whether they are 
 caused by ordinary bacteria the pathogenic role of which has been 
 demonstrated by experimentation. 
 
 The same reflections are applicable to the acute spinal paralysis 
 of adults, the symptoms and course of which recall exactly those of 
 infantile paralysis and which may also prevail in epidemic form. In 
 the report given by Leegaard fifty-four individuals were affected. 
 The greatest number of cases are observed, on the one hand, under 
 four years of age, and, on the other, between fifteen and nineteen 
 years; a few patients, however, were above thirty. Of the fifty-four 
 persons attacked, twelve recovered completely : thirty retained some 
 paralysis; ten remained impotent, and two died. 
 
 Myelites in Various Infections. Myelites which develop in the 
 course or in consequence of infectious diseases may be divided into 
 two groups according as they are diffuse or systematic. 
 
 Diffuse myelites are very frequent, but they may at times t> s 
 slight as not to be revealed by any symptom. Widal and Bezancon 
 
 27 
 
418 INFECTIOUS DISEASES. 
 
 have found, for example, alterations in the cells of the anterior 
 horns in two variolar patients who, during life, had not presented 
 any spinal symptom. One is thus led to ask whether certain motor 
 difficulties experienced by convalescents and attributed to asthenia 
 do not depend upon superficial and curable lesions of the spinal cord. 
 
 In certain instances myelitis appears at the beginning of an infec- 
 tion. Such is particularly the case in variola, The intense back- 
 ache of which patients complain indicates the early participation of 
 the spinal cord in the process. There may be nothing more than 
 congestion. It is known, moreover, that backache occurs at the 
 onset of other eruptive fevers. In fact, all the infectious diseases 
 might be cited in this connection. Typhoid fever, influenza, pneu- 
 monia, erysipelas, dysentery, and gonorrhea are among the most 
 frequent, Diphtheria might be added, although authorities are 
 greatly inclined to-day to refer the paralyses of this disease to 
 peripheral neuritis. 
 
 The symptomatology is. extremely variable. In some instances 
 disorders rapidly develop, as in acute ascending paralysis ; in other 
 cases the manifestations are at first diffuse, but subsequently become 
 localized in a certain part of the spine. At times the victim is 
 paralyzed in the lower extremities or only in a limited part of the 
 body. In the presence of these various paralyses the question arises 
 as to whether they are due to real medullary lesions or to neuritis, 
 neurosis, or hysteria. The question often remains unanswered. 
 
 There can be no doubt in the case of a well-determined disease, 
 such as tabes dorsalis. The role of infection in the genesis of this 
 myelitis is incontestable. Numerous statistics show that nearly 
 all sufferers from tabes have a syphilitic history. This fact, how- 
 ever, does not warrant the conclusion that locomotor ataxia is a 
 syphilitic disease, since it does not respond to the specific treatment, 
 and at the necropsy no lesion is found presenting the characteristics 
 of syphilis. In nine out of ten cases of tabes syphilis is said to be 
 found in the antecedents. Granted. The tenth case, however, is 
 sufficient to prevent tabes from being held as a syphilitic disease. 
 Syphilis does act, but only as an auxiliary cause. Other causes 
 could, however, play the same role, and this is proved to be true 
 by the fact that a great number of infections, such as pneumonia, 
 typhoid fever, cholera, variola, etc., are often found in the antece- 
 dents of non-syphilitic sufferers from tabes. 
 
 "We must likewise note that progressive muscular atrophy ensues 
 
INFIjlJUNdH OF INFECTIONS UPON TEE ORGANISM. Hfl 
 
 sometimes after infections such 8 typhoid fever, mea le . rheuma- 
 tism, cholera, and pneumonia. 
 
 Lastly, Desnos and Babin ki nave shown syphili among the 
 causes of syringomyelitis. This affection hat sometime* followed 
 typhoid fever, rheumatism, pneumonia, gonorrhea, or even a simple 
 bronchitis. 
 
 Infectious Neurites. 
 
 The participation of the peripheral nerV0U£ ; tem in infectious 
 processes is evidenced by the frequency of neuralgias, notably facial, 
 sciatic, and intercostal neuralgias. Acute as well as chronic infec- 
 tions often give rise to these nervous manifestations. They have 
 been observed as a result of influenza and pneumonia. I have met 
 with several examples consecutive to scarlatina and erysipelas. 
 Their frequency in malaria and syphilis is well known. In all cases 
 of rebellious sciatic neuralgia the cause of which cannol be deter- 
 mined, Landouzy advises a search for tubercular manifestations. 
 
 Herpes zoster sometimes develops in consequence of an infection, 
 notably erysipelas and scarlatina. The frequency of primary herpes 
 in certain seasons, the febrile movement accompanying it, and the 
 immunity conferred by a first attack seem to give a solid basis to 
 the opinion that this eruption depends upon an infection of the 
 nervous system. 
 
 The motor disorders caused b}- peripheral neuritis must lie care- 
 fully studied. They are often contrasted with similar disturbances 
 produced by medullary lesions, and some authorities have attempted 
 to establish differential characters between myelitis and neuritis. 
 It is, perhaps, an error to separate too widely the two process - 
 The peripheral alterations possibly depend upon some central lesion, 
 though the latter may be slight and easily escape notice, or be 
 inappreciable by our present means of investigation. 
 
 Infectious polyneurites are often divided into two groups, accord- 
 ing as they occur in the course of a definite disease or independently. 
 
 Secondary infectious polyneurites are observed in connection with 
 all acute infections. The}* at times appear in the course of chronic 
 infections, such as paludism, tuberculosis, syphilis, and lep- 
 It is known that in the last-named disease the bacilli become 
 localized in the nerves and there produce small noduL - 
 
 Primary polyneurites may be acute or chronic. In the former 
 case they constitute a clinical type described by Leyden; in the 
 
420 IXFECTIO US DISEASES. 
 
 latter instance it is a malady of hot countries: beriberi. Balz and 
 Scheube found in the affected nerves a diplococcus, cultures of 
 which gave rise to peripheral neuritis when inoculated into dogs 
 and rabbits. 
 
 Acute infectious polyneurites sometimes occur in epidemic form, 
 as Eisenlohr has observed the disease in Hamburg. They often begin 
 suddenly by intense pain in the extremities, notably in the lower, 
 and are attended by fever, at times delirium, insomnia, and a certain 
 degree of stupor. There is albumin in the urine, and the skin may 
 present a subichteric aspect. 
 
 Then paralysis, accompanied with shooting pains, supervenes. 
 Later, sensation is diminished, and may sometimes advance to 
 anesthesia, especially at the periphery of the limbs. The paralysis 
 is of the flaccid kind, without contracture, and attacks the lower 
 extremities, although in some cases it may assume an ascending course 
 and also involve the upper extremities. The muscles soon become 
 atrophied, while fat accumulates in the subcutaneous cellular tissue. 
 Tendon reflexes are diminished or abolished. Electric contractility 
 of the muscles is generally diminished, the reaction of degeneration 
 is often observed. In cases in which the pneumogastric is in- 
 volved, death may ensue by asphyxia at the end of a period varying 
 from six clays to a month. In other cases the process is arrested 
 and subsides; the patient recovers completely or else retains some 
 paralyses. 
 
 Pseudotabetic polyneurites are readily distinguished from loco- 
 motor ataxia by the gait of the patient, the legs being lifted high 
 instead of groping, by the absence of visceral disturbances, and by 
 favorable evolution of the lesions. 
 
 Pseudotabes has been observed in consequence of a great number 
 of infectious diseases, and notably after diphtheria and erysipelas. 
 As, however, these two diseases are most frequently attended by 
 paralytic manifestations of all descriptions, it is interesting, to devote 
 a special study to them. 
 
 Diphtheritic Paralyses. In my personal statistics I find in a total 
 of 216 cases of diphtheria in adults 42 attacked by paralysis. In 
 39 of these the palate was paralyzed, in 12 the extremities were 
 also involved. In nearly half of the cases paralysis appeared two 
 to fifteen clays, exceptionally three to four weeks, after the beginning 
 of the disease. 
 
 Motor disturbances may be accompanied by disorders of sensation 
 
INFLUIMCH of INFECTIONS UPON THE ORGANISM. 121 
 
 and of the senses. One patienl I" 1 ta te, so thai agar, salt, and 
 quinine sulphate, when applied to the tongue, had a slightly suj 
 
 taste to hi 111. 
 
 Trousseau has laid stress, though with manifest exaggeration, 
 upon tho wandering character of diphtheritic paralyses. In fact, 
 one is at times astonished a1 modifications occurring suddenly. A 
 patient under my observation Buffering from post-diphtheritic 
 pseudotabes was almost Incapable of walking. A fire occurred 
 in the ward where he was lying, and soon ii was so full of smoke 
 that (hose who ran to rescue him were forced to fall back. Another 
 attempt was about to be made when the patienl was seen coming 
 out quietly. Under the influence of the emotion, paralysis had 
 suddenly vanished, and recovery proved to be permanent. 
 
 Fatal termination results from the entrance of food into the 
 respiratory tract. This aecidenl is particularly frequenl when 
 the glottal muscles are paralyzed coincidently with the palate. The 
 resu.lt is a bronchopneumonia or a pulmonary gangrene, invariably 
 terminating in death. Death occurs by asphyxia, al times by 
 syncope. 
 
 It is to be noted that the employment of the esophageal bougie, 
 far from preventing the passage of food into the respiratory tract, 
 seems to favor this accident; the fluids introduced into the stomach 
 are soon rejected by regurgitation, and enter the trachea. I have 
 seen two patients succumb in this manner. 
 
 In certain cases death results from an unexpected attack of 
 syncope. A man, twenty-five years of age, who had paralysis of 
 the palate, died suddenly twenty-four hours after the beginning of 
 the disease. Histological examination demonstrated the integrity 
 of the bulbar centres ami pneumogastrics. but revealed a diffuse 
 myocarditis, which had probably played the principal role. 
 
 There is at present an inclination to believe that diphtheritic angina 
 is the only kind of sore-throat capable of giving rise to para;; - s. 
 Some of my observations show this opinion to be exaggerated. A 
 woman, of twenty-five years of age, who had recovered from a 
 phlegmon of the tonsil, retained a paralysis of the palate: the fluids 
 flowed through the nose, and the patient was forced to incline the 
 head backward in order to swallow. This paralysis disappeared 
 suddenly four days later. In face of this sudden termination one 
 may think of a hysterical phenomenon : no stigmata of this neurosis 
 were found, however. 
 
422 INFECTIOUS DISEASES. 
 
 Erysipeloid Paralyses. Next to diphtheria erysipelas is, perhaps, 
 the disease which most frequently gives rise to paralytic disturb- 
 ances. My former interne, Dr. Crochet, made an excellent study of 
 it in his thesis (1S95). 
 
 Trousseau observed impotence of the dorsolumbar muscles con- 
 secutively to diphtheria, rendering vertical position impossible. I 
 observed a young girl of sixteen years, convalescent from a severe 
 erysipelas, who was incapable of sitting up in her bed or raising her 
 head. On the following day she was able to get up and walk when 
 supported, but she had a tabetic gait. There was also a persistent 
 paratysis in the nape of the neck. The phenomena were gradually 
 ameliorated, and the patient recovered in a fortnight. 
 
 I have noticed the appearance of painful spasms and marked 
 impotence in the lower extremities in two convalescents from ery- 
 sipelas. One of them, a woman of twenty-one years, without any 
 nervous antecedents, suffered from shooting pains in the legs after 
 an erysipelas of moderate intensity. She could not stand on her 
 feet for more than five minutes at a time; when she rose, her legs 
 remained in a position of semiflexion, and her head fell upon her 
 chest. At the end of a month all these symptoms were almost 
 completely cured. 
 
 In some cases peripheral paralyses occur. A manifestation of 
 frequent occurrence consists in a combination of paralysis of the 
 lower extremities and cutaneous hyperesthesia and exaggerated 
 reflexes. In some instances the upper extremities are also involved. 
 Paralysis of accommodation preventing vision at close range, facial 
 paralysis, amblyopia, and diminution in auditory acuteness are 
 likewise among the possible events. 
 
 Scarlatinal Paralyses. Of all the eruptive fevers, scarlatina is 
 the most often productive of paralytic disturbances; still, these are 
 rare. In a total of 2213 cases I found only four cases of incomplete 
 paraplegia. In one of these instances, a man, who suffered from 
 scarlatinal angina, developed paralysis of the palate on the second 
 day. Three days later the lower extremities were slightly involved; 
 next the right arm was attacked; movement was still possible, but 
 difficult and maladroit. These symptoms disappeared in ten days. 
 In the antecedents of this man was found the occurrence of a transi- 
 tory paralysis occurring four years previously as a result of some 
 work done in compressed air. 
 
INFLUENCE OF INFECTIONS UPON THE ORGANISM. 123 
 
 Post-infectious Neuroses. 
 
 The influence of infection as an occasional cause of neuro 
 present well known, in mosl ca es thedi order are ol a h) fcerical 
 character. In a man convalescenl from scarlatina attackf of con- 
 vulsions occurred, in another, ane the ia oi general en ation and 
 of the senses developed after erysipelas . [n still other cases, trem- 
 bling is observed; such was the ca e in a man, ixty nine yean of 
 age, 1 whose trembling was firsl mistaken as paralysif agitans. The 
 rhythmical oscillations of the forearms were repeated l l ( ) to 150 times 
 a minute. When, however, he attempted to carry a glass of 
 to his mouth the trembling changed its character; instead of ceasing 
 during the movement, as is (he case in paralysis agitans, the range 
 of the oscillations was exaggerated, so that the water was thrown 
 out and the patient struck his face. The patellar reflexes, on the 
 other hand, were diminished. The uncertain diagnosis was singu- 
 larly facilitated by the study of his antecedents. He belonged to 
 a family of nervous people. His father, of a violent tamper, had 
 committed suicide at the age of eighty-six years, because he had 
 become incapable of riding a horse. One of his sisters has attacks 
 of hysteria. During his long life he had been sick only twice: he 
 had two attacks of pneumonia, and here is the curious series of 
 accidents which were produced by these infections: 
 
 His first attack of pneumonia occurred in 1S60, at the age of 
 thirty-five years. While being treated under Bouillaud lie was 
 subjected to blood-letting fourteen times in five days. In spite of 
 such treatment, the patient was too agitated, and therefore he was 
 isolated. This measure irritated him: he was furious and, for the 
 first time in his life, he had a nervous paroxysm, fought, cried, and 
 all ended in profuse sweating: he then fell into a sound sleep. On 
 awakening the following day he noticed that he could not move 
 his lower extremities, and had retention of urine. He recovered 
 from his pneumonia two days later, but his paraplegia persisted 
 unmodified. For a year and a half he wandered from hospital to 
 hospital, and finally was admitted into the wards of Behier. who 
 prescribed douches and extract of valerian. Recovery was complete 
 in forty-five days. The man resumed his occupation and again 
 became as quiet as ever, no longer presenting any nervous spells. 
 
 1 Roger. Du tremble men t hysterique. La s?maiue medicate. Nov. .5. 1S93. p. -522. 
 
424 INFECTIOUS DISEASES. 
 
 Thirty-three years later, in 1S93, this man had another attack of 
 pneumonia. He easily recovered from it, but he experienced an 
 increase in the urinary disorder from which he had suffered for some 
 time and which was due to hypertrophy of the prostate gland. He 
 was convalescent when he tried to catheterize himself, and, not 
 succeeding, he became impatient, and suddenly had a nervous 
 paroxysm similar to the one he experienced in 1860. When he 
 became conscious he found his extremities trembling intensely. The 
 lower limbs were rapidly cured, but the disorder persisted in the 
 upper extremities, and it was for this reason that the patient asked 
 to be admitted into our wards in 1893. 
 
 There can be no doubt as to the hysterical character of the pheno- 
 mena, both paralyses and trembling. This diagnosis was confirmed 
 by the fact that our patient presented a slight right hemianesthesia 
 and a hysterogenic zone on the testicle of the same side. The 
 absence of ocular disturbances, the diminution of the patellar reflex, 
 and, on the other hand, the absence of the characteristic stiffness, 
 were not consistent with the idea of spinal sclerosis and paralysis 
 agitans, diseases the coexistence of which with hysteria is not im- 
 possible. Further developments fully proved the correctness of our 
 diagnosis. We prescribed a daily dose of 4 grains of extract of 
 valerian. There was improvement in a few days. One day, after 
 catheterization, the patient had an intense febrile paroxysm. The 
 fever did not last, but exerted, it seems, a favorable influence upon 
 the nervous symptoms, which gradually diminished, and between 
 June 27th, the day when the fever occurred, and July 3d it had 
 almost completely disappeared. He could hold a large object, 
 such as a glass, and could therefore drink all right, but he could 
 not control his movements when handling a small article like a 
 spoon, and hence he was not yet able to eat his soup. From this 
 moment onward I noted his improvement day after day, by causing 
 him to write. At first he was able to use only a pencil, and later 
 a pen. On awakening in the morning, while his bladder was full, 
 he wrote with great difficulty; the characters were often indented 
 and jagged as in paralysis agitans. A few minutes after he had 
 been catheterized he was able to write in a correct manner. These 
 last manifestations also gradually vanished, and the man was com- 
 pletely cured by the end of July. 
 
 This observation seemed to me interesting in more than one 
 respect, and particularly by reason of the conditions which governed 
 
INFLUENCE OF INFECTIONS UPON THE BO AN 18 M. \j_:, 
 
 the development of the morbid phenomena. Here i a man who 
 presented no hysterical manifestation whatever until the age of 
 thirty-five years, but his nervoui y tem had an hereditary taint. A 
 pneumonia supervened and broke the unstable tate of equilibrium. 
 Simple anger sufficed to give rise to the gravest manifestations. 
 Then order was again restored in the oervou • tem, and the man 
 led a perfectly calm life for thirty-three years, until al the age ol 
 sixty-nine years when man is commonly secure from hysteria 
 hysterica] incidents once more occurred, brought about by similar 
 causes. Much has been said in recent yen- regarding the role of 
 infection in the development of hysteria; there can be found do 
 observation more demonstrative than the foregoing. 
 
 In this connection I may rile the r;ise of a young girl, aged 
 enteen years, who, after a facial erysipelas, was suddenly attacked by 
 trembling in the lower extremities and the forearms. A few mo nth- 
 after, as the result of an hysterical attack, the trembling suddenly 
 disappeared. This abrupt termination and the appearance of hys- 
 terical attacks, which recurred once :i month thereafter, confirm the 
 diagnosis of post-infectious hysterical trembling made in the old 
 man's case. 
 
 In the case of a girl eight years of age, five days after recovery 
 from scarlatina, choreiform movements with anesthesia in the ex- 
 tremities of the left side made their appearance. A few days later 
 a well-marked hysterical paroxysm occurred. In fifteen days all 
 symptoms disappeared. 
 
 Another patient, also convalescent from scarlatina, developed 
 spasmodic paraplegia in the lower extremities, with hyperesthesia, 
 exaggeration of the patellar reflexes, and epileptoid trepidation. 
 These manifestations disappeared within a fortnight. 
 
 Among hysterical manifestations observed after infections I may 
 mention a case of aphasia following measles in an eight-year-old 
 child, and two cases of astasia-abasia following scarlatina. One of 
 the latter concerned a woman for ten years subject to hysterical 
 attacks. The manifestations soon disappeared. 
 
 Epilepsy, Tetany, Chorea. Like hysteria, epilepsy may appear 
 in consequence of acute infections, such as scarlatina, measles, 
 variola, typhoid fever, and in the course of chronic infections — 
 paludism and syphilis. The same is true of neurasthenia, which at 
 times develops or is aggravated after infections. Paralysis agitans 
 has also been observed on the occasion of a typhoid fever, acute 
 
426 ISFECTIOUS DISEASES. 
 
 articular rheumatism, and intermittent fever. Tetany has been 
 noted under the same circumstances, notably after the eruptive 
 fevers, cholera, and pneumonia. Of all the neuroses chorea occurs 
 most frequently under these conditions. Rheumatic infection — 
 since rheumatism is now admitted to be an infection — may be held 
 to be the most frequent cause of chorea. It seems, however, that 
 chorea is to rheumatism what tabes dorsalis is to syphilis : it is the 
 chief occasional cause, nothing more. There are many observations 
 of choreic children who have never had rheumatism, but who have 
 just suffered from some acute disease, an eruptive fever, notably 
 measles, typhoid fever, cholera, whooping-cough, or influenza. 1 
 
 In a total of 300 chorea cases Triboulet recognized 100 patients 
 who developed the neurosis in consequence of some infection. On 
 the other hand, on tabulating various statistics, I find rheumatism 
 in the etiology of chorea in only 22 per cent, of the cases. It may, 
 therefore, be concluded that rheumatism plays a considerable role, 
 but is far less important than many authorities assert. 
 
 Infectious Meningites. The meninges, like the other parts of the 
 organism, may be infected primarily or secondarily. The type of 
 primary meningitis is represented by the epidemic cerebrospinal 
 meningitis due to the meningococcus intracellularis of Weichsel- 
 baum. This pathogenic agent invades the economy through the 
 nasal fossae. Primary meningitis may also be dependent upon 
 common bacteria ; it is usually caused by the pneumococcus, and 
 represents the localization of a bacteremia. 
 
 The investigation of microbes in meningitis acquires to-day con- 
 siderable interest, since it is possible to puncture the spinal meninges 
 during life and examine the spinal fluid. By this new procedure 
 it has been found that out of a total of 100 cases of meningites 60 
 were due to the pneumococcus (Netter) . This micro-organism may 
 give rise to primary meningitis, or else invade the meninges in conse- 
 quence of a pulmonary localization ; meningitis is said to occur once 
 in two hundred cases of pneumonia. The pneumococcus may 
 likewise act as a secondary agent in the course of another infection, 
 notably erysipelas. 
 
 Next comes the streptococcus. It produces the meningitis of 
 puerperal infections and of pyemias. It is also the microbe most 
 commonly found in meningitis consecutive to lesions in the ear. 
 
 1 Triboulet. Du role possible de 1 'infection dans la pathologie de la choree. These 
 de Paris, 1893. 
 
INFLUENCE OF INFECTIONS UPON THE ORGANISM. \z7 
 
 Bacilli, notably the typhoid bacillui , Friedlaender'i bacillus, and 
 the bacillus of influenza may also induce meningeal inflammation . 
 Rheumatic meningites seem to represenl a localization of pseudo- 
 
 rlicuiii;iJ,isnis /. <■., of pyemias. M i al o to be remembered thai 
 the association of these various microbes in the same focus is not 
 
 an uncommon cvcnl . 
 
 Among the discuses treated in our wards, erysipelas furnished 
 the strangest results. In a total of 2411 patients we observed 
 three cases in which the necropsy disclosed a suppurative meningitis. 
 It was natural to refer the lesion of the meninges to streptococcic 
 infection; bacteriological examination demonstrated, however, thai 
 the process was one of secondary pneumococcic infection. 
 
 Meningitis has been altogether exceptional in connection with 
 other infectious diseases treated by us. We find only four obser- 
 vations of this kind, which are very few in view of the large number, 
 7778, not including erysipelas, contained in our general statistics. 
 In two instances meningites were consecutive to suppurative otitis. 
 
 Influence of Infection upon Neuropathies. The fact thai an 
 infection may give rise to nervous disturbances has repeatedly been 
 referred to. It produces hysterical, choreic, epileptic or exoph- 
 thalmic manifestations in predisposed subjects. Occasionally it 
 arouses a past disorder. Thus in a tabetic subject of forty-five 
 years of age, who had a syphilitic history, an attack of erysipelas 
 caused the return of fulgurating pains, from which the patient had 
 not suffered in several years. In other instances infection engenders 
 morbid symptoms in apparently healthy individuals, and thus reveals 
 the existence of a latent disease. Such was the case in a man of 
 forty-eight years, who had had syphilis twenty-six years before. 
 After an attack of erysipelas he complained of very intense hyper- 
 esthesia and lancinating pains in the lower limbs. Examination 
 then revealed exaggerated cutaneous reflexes, abolition of tendon 
 reflexes, inequality of the pupils, suppression of accommodation to 
 light, slight ataxia in movements, and inability to walk with closed 
 eyes. The phenomena of cutaneous hyperesthesia soon subsided, 
 but the other manifestations, which became apparent at the time 
 of the erysipelatous attack, continued their evolution. 
 
 On the other hand, an intercurrent infection may cause the dis- 
 appearance of pre-existing nervous symptoms. It may thus act 
 upon hysteria, epilepsy, and may. perhaps, even improve organic 
 lesions. A woman of forty-four, who had been treated in a hospital 
 
428 IXFECTIO US DISEASES. 
 
 for two vears for a paraplegia attributed to myelitis, came under my 
 observation. During convalescence from an erysipelas the reflexes 
 which had been abolished reappeared, paralysis diminished, and 
 two weeks later the patient walked with ease. No sensory disorder 
 or hysterical stigmata existed in this case. Unfortunately, in the 
 majority of cases, amelioration is not permanent. Contrary to 
 expectation, infections and inoculation of microbic toxins do not 
 cure epilepsy. 
 
 Action of Infections upon the Organs of Sense. 
 
 The study of the organs of sense usually goes with that of the 
 nervous system. 
 
 The frequency of oculo-nasal catarrh at the beginning of measles 
 is familiar. It figures among the initial symptoms, and is of much 
 diagnostic value. It may, however, be absent, or so slight as to 
 readily escape observation. On the other hand, other infections, 
 notably scarlatina and variola, are sometimes attended by the 
 symptom under consideration. The physician must, therefore, be 
 awake to this double source of error. 
 
 During the stationary period of and convalecsence from infectious 
 diseases, complications, generally of a suppurative character, are 
 very frequently observed in the various organs of sense. Purulent 
 rhinitis occurring in scarlatina is sometimes so profuse as to suggest 
 glanders. This complication is quite grave, as thirteen of such cases 
 ended fatally. 
 
 The nasal fossa? may also serve as entrance to many other patho- 
 genic germs. In several instances in which streptococci had engen- 
 dered slightly purulent inflammation in the nose, erysipelas developd 
 a few daj^s later. The development of streptococcic dermatitis is 
 far oftener preceded by coryza than by angina. 
 
 Ocular suppurations are rare. Catarrhal conjunctivitis is fre- 
 quently observed, but it is slight and transitory, except in variola. 
 In this infection conjunctivitis is frequent and grave. Inflammation 
 too often extends to the cornea, and opacity may be produced 
 within twenty-four hours. This involvement may occur even when 
 stagnation of the septic fluids is prevented by frequent lavage. 
 Keratitis may be superficial or ulcerative. It may terminate in 
 perforation, with hernia of the iris, or the infection may extend to 
 the deeper parts, producing purulent disintegration of the eye and 
 final atrophy. 
 
INFLUENCE OF INFECTIONS UPON THE ORGANISM. 129 
 
 Erysipelas also may give rise to le ion of the eyelid . ab <■• ■ 
 and even gangrene, bul .'ill these ub ide very readily. 
 
 Otitis tiic(li;i is very rare in variola. Out of a total "I 755 c 
 ending in recovery I find il noted only in ten instance , Suppuration 
 of the ear is sometimes observed in ery ipela . bul i imp] 
 involvemenl of the external ear, and is devoid of gravity. 
 
 In the majority of cases otitis occur al the end of the disease or 
 during convalescence. The beginning i- marked by pain and 
 persistence or recurrence of fever. Whether the tympanum is 
 
 opened spontai usly or by paracentesis, the symptoms subside 
 
 with satisfactory rapidity, and in mosl cases recovery i- obtained 
 and hearing is preserved intact. Some patients, however, left the 
 hospital with a piirulenl discharge. In -nine rare instances otitis 
 gives rise to alarming manifestations. One patienl exhibited 
 meningeal disturbances which rapidly yielded to the influen© ol 
 bromide. Three others, suffering from post-rubeolar otitis, de- 
 veloped mastoiditis and were transported to a special hospital. 
 Finally, two children died of septicemia as a result of post-rubeolar 
 otitis. 
 
 Apart from the lesions resulting from propagation or a superadded 
 infection, disorders which seem to be dependent upon some toxic 
 central lesion may sometimes occur. Thus, during convalescence 
 from the most varied infections, amaurosis, optic neuritis, deafness 
 or vertigo due to labyrinthine lesions, may occur. According to 
 my statistics, however, such manifestations are exceptional. 
 
 Cutaneous Manifestations in Infections. 
 
 In the course of infections the nutrition of the skin is more or as 
 profoundly disturbed. This is clearly evidenced by the dryness and 
 frequent desquamation of the integument, even in the absence of 
 eruptive fevers, the frequency of suppurations and. in a great number 
 of instances, the secondary disorders occurring in the adnexae of the 
 skin — the loss of hair and the trophic alterations of the nails, which 
 become brittle or fissured. These various manifestations are a] 
 ciable, particularly in those infections which have a certain duration. 
 They are most readily studied in typhoid fever. During convales- 
 cence, especially in children, a furfuraceous desquamation of the 
 lateral regions of the body occurs. 
 
 In some instances the cutaneous infection is of external origin, 
 and sometimes appears alone. At other times it occurs in connec- 
 
430 IXFECTIO US DISEASES. 
 
 tion with an infection which, by disturbing the organism, has played 
 the role of a predisposing cause. 
 
 In another group are to be placed those cutaneous infections 
 which, unlike the preceding, are of inward origin, and are effected 
 from within outward. The same microbes are sometimes concerned 
 in both cases, and the symptoms also may be identical. The 
 mechanism, however, is altogether different, and the evolution 
 follows a course peculiar to each group. The cutaneous lesion is the 
 result of a discharge tending to throw out the infectious germs 
 which have invaded the organism. Not only the figurate elements, 
 but also the soluble substances are thus eliminated by the skin. 
 This leads us to a third group of manifestations — i. e., symptoms 
 or complications of a toxic order occasioned by the poisons 
 which are produced in the economy, and may be compared with 
 similar manifestations observed in a great number of exogenic in- 
 toxications. 
 
 Excepting the cases in which the pathogenic agent is directly 
 inoculated, as occurs in tuberculosis, glanders, and, at times, with 
 the pyogenic cocci, the apparently spontaneous development of a 
 cutaneous lesion is always referable to some previous disorder in 
 the organism. There has been an infection, some digestive disturb- 
 ance, or a nutritional disease, such as diabetes. In subjects thus 
 predisposed there may often be found some occasional cause — 
 friction, slight traumatism, biting, superficial excoriation, applica- 
 tion of irritating substances, exposure to physical agents, heat, light, 
 and, finally, cold. While it can no longer be admitted that cold is 
 of itself sufficient to create erysipelas, it is certain that it singularly 
 predisposes to it. 
 
 One remarkable character of cutaneous infections is the facility 
 with which they return; relapses and recidives are almost the rule. 
 Repeated recurrence of furunculosis and erysipelas are familiar illus- 
 trations of this fact. As far as erysipelas is concerned, it is certain 
 that the infection is not terminated after an apparent recovery, if 
 certain vasomotor disorders persist. These disorders are some- 
 times transitory and sometimes permanent. In the former instance, 
 a slight occasional cause, a movement, an emotion, at times simply 
 the exercise involved in speaking, is required in order to cause the 
 face to become scarlet. In other cases the patient retains a perma- 
 nent red color. At the end of several weeks this color still persists. 
 The patient believes himself completely cured; as soon, however, 
 
INFLUENCE OF INFECTIONS UPON THE ORG A -i If, \\>,\ 
 
 as he becomes tired, or expo e him elf bo cold, b new attack of 
 erysipelas occurs. 
 
 There is another group of infectious le ion ( 't the kin which 
 already stated, are due to microbic discharge. Pyodermia 
 frequent in children, the germ commonly penetrating from without. 
 In certain cases, however, analogous Lesion* are brought about by a 
 galactophoritis of the mother: the pus cocci are ingested by the 
 child with the milk, and are subsequently eliminated by the .'-kin, 
 causing the development of pustules. 
 
 Lesions produced by microbic elimination through the Bkin an 
 times erythematous or papular. The type U furnished by syphilides. 
 The contagious character of papular syphilides, al leasi 'Alien they 
 are moist, leads to the conclusion (hat they represenl a Localization 
 of the morbid agent. A similar mechanism has be< n suggested with 
 regard to the lenticular roseate patches of typhoid fever. By 
 puncturing them Neuhauss claims to have found the bacillu 
 Eberth; the researches of Chantemesse, however, have always been 
 negative. 
 
 The most interesting microbic eruptions are those of varicella and 
 variola. These differ clearly from each other by their objective 
 characters. In varicella the eruptive element is constituted by an 
 oblong bulla with irregular borders and a clear, transparent fluid. 
 This bulla is an elevation of the most superficial part of the skin, 
 raising only the epidermis. In variola, the eruption assumes the 
 .form of a papule, then that of a pustule, which is rounded, hard, and 
 seated deeply in the skin. Varicellar eruption appears in successive 
 outbreaks, so that the most closely situated cutaneous lesions are 
 of different ages; crusts are found alongside of transparent bulls. 
 In variola the lesions are of the same age, at least in the same 
 region; for the eruption may already be crusty upon the face and 
 hands, while it is yet pustular upon the legs. It is also to be re- 
 membered that every papule does not follow its complete evolution; 
 hence, at the end of the disease the appearance is not exactly 
 similar, although all the papules may have appeared simultane- 
 ously. 
 
 Exanthemata of the Eruptive Fevers. The study oi the eruptive 
 fevers raises a few problems of great interest which cannot be solved 
 in a definitive maimer until the microbic agents producing them are 
 known. For the time being a few considerations may be presented 
 on this subject. 
 
432 INFECTIOUS DISEASES. 
 
 The eruption, which is considered so characteristic of the group 
 of eruptive fevers, is not indispensable. There are on record numer- 
 ous cases of slight fevers, of measles and notably of scarlatina, 
 without cutaneous manifestations. On the other hand, epidemio- 
 logical investigations have shown that individuals have contracted 
 scarlatina from patients who suffered simply from anginas; on the 
 other hand, scarlatinal patients have transmitted simple anginas. 
 Several of our nurses attending scarlatina patients have suffered 
 from sore throats without any eruption or desquamation whatever. 
 
 In order to explain these facts, several hypotheses may be ad- 
 vanced. These apparently non-scarlatinal anginas are either slight 
 scarlatinas, or else a common microbe, the streptococcus, exalted in 
 the throat of a scarlatinal patient, may produce an angina in other 
 individuals. On the other hand, the microbe of a simple angina 
 may favor the development of the scarlatinal germ. Finally, 
 another hypothesis consists in considering scarlatina as dependent 
 upon a streptococcus which gives rise to typical scarlatina or to a 
 simple angina, as the case may be. 
 
 If the last theory is admitted, scarlatina would accordingly be 
 an angina with erythema. Several arguments may be advanced in 
 support of this conception. Even leaving aside those arguments 
 which could be derived from the etiology, the cases of simple anginas 
 with erythema may still be cited. These are not cases of scarlatina, 
 since the eruption has not the same objective characters, no desqua- 
 mation takes place, and the tongue is not red and raw-looking. 
 Moreover, the eruption is contingent, and the skin does not contain 
 the germ of the disease : the microbe is found in the saliva. Finally, 
 when the throat affection is absent, and this is exceptionally the 
 case, there exists a microbic focus where the erythogenic toxins are 
 elaborated; it is a cutaneous or mucous membrane wound, as in 
 surgical and puerperal scarlatinas. On the other hand, bacterio- 
 logical investigations detect in the throat and, if the patient dies, 
 in the blood, in case of a complication occurring in the secondary 
 focus, one and the same microbe. This microbe is likewise found 
 in the urine in case of nephritis. The microbe in question is the 
 streptococcus, which is held by some to be a common one; by others, 
 one possessed of special characters. It is conceivable that, taking 
 ground on these facts, certain authorities should have considered 
 scarlatina as a streptococcic infection; a microbic focus is, in most 
 cases, developed in the throat, and the toxins which are there pro- 
 
INFLUENCE OF INFECTIONS UPON THE ORG I ' ■/ If |.;.; 
 
 duced give rise to the erythema, the importance of the eruption 
 thus being reduced considerably. Such is the view advanced first 
 by Klein, and subsequently well developed by Berge\ 
 
 The hypothesis is seductive. For it- demonstration, however, i' 
 should be established that the organism of an individual Buffi 
 from or cured of scarlal inaexerl a pedal influence upon th< 
 coccus. The agglutinating action of the serum of scarlatinal patients 
 should, for example, be Btudied. The Btreptococci of scarlatina, 
 however, do not occur muted in masses, and il is, therefore, difficult 
 to study their agglutination. At my suggestion, Dr. Courtain 
 attempted to inject into rabbits the urine of scarlatinal patients, and 
 noticed that at (lie end of some time the serum of these .'uiirnol- 
 acquired a certain protective power against the streptococc 
 scarlatina. The experiments of the author, however, are qoI 
 sufficiently numerous to render the results conclusive. 
 
 The same reasoning is applicable to measles. This disease is 
 especially contagious in the catarrhal stage prior to the appearance 
 of the eruption. This fact leads to the question whether the pr< 
 is not an infection of the nasal mucous membrane giving rise second- 
 arily to a toxic erythema. The researches of Dr. Lesage seem to 
 confirm this view. 
 
 Mechanism and Variability of Infectious Erythemata. The 
 frequency of erythemata in the course and as a result of the most 
 varied infections demonstrates that microbic toxins exert a very 
 marked influence upon the vasomotor centres. They stimulate the 
 vasodilators and enable them to react with the greatest facility. 
 I have already referred to a new proof of this action, viz., the cutane- 
 ous redness persisting after erysipelas. 
 
 This action of infections, and notably of streptococcic infections, 
 accounts for the curative influence exerted by some of them. Rebel- 
 lious skin lesions, ulcers upon the legs, and lupuses have been seen 
 to heal in consequence of an intercurrent erysipelas. On the other 
 hand, vasomotor disturbances may awaken dormant lesions: in one 
 case an erysipelas of the face seemed to renew an eczema of the 
 hands. In a man, twenty-three years of age. erysipelas provoked 
 a renewal of papular syphilides. This man had suffered a year 
 before from an indurated chancre and a roseola. The fresh cutaneous 
 manifestations yielded in a week to specific treatment. 
 
 The erythema of eruptive fevers varies in intensity, sometimes 
 without any apparent cause, sometimes for reasons that are readily 
 
 28 
 
43-4 INFECTIOUS DISEASES. 
 
 comprehensible. Thus in children suffering from whooping-cough 
 the rubeolar eruption is remarkable for its intensity. I had the 
 opportunity to observe two patients who had been taking copaiva 
 for a few days for gonorrhea, This medicine, which is capable of 
 producing erythemata, imparted some particular characters to the 
 eruption of an intercurrent measles. One of them, eighteen years 
 of age, presented an eruption remarkable for the existence of very 
 large patches of red purple color on the chest, abdomen, and the 
 extremities. The modification was more profound in the other case, 
 a young man twenty-one years old, who had upon his face the 
 classical eruption, while upon the thorax the lesions were confluent 
 and intense^ red, recalling the exanthema of scarlet fever; upon 
 the abdomen, thighs, and arms were seen extensive slightly ecchy- 
 motic patches of a livid red hue, disappearing incompletely on 
 pressure . 
 
 In some instances the intense congestion terminates in hemorrhage. 
 The eruption is then slightly petechial, though there may be no other 
 serious manifestation. In certain cases of scarlatina or measles the 
 eruption does not disappear on pressure; the skin becomes white, 
 but a multitude of small red spots can be seen. These minute 
 hemorrhages, even when extensive, have no grave significance. 
 Similarly, in variola the so-called scarlatiniform rash, which has 
 been well distinguished from true hemorrhagic rash, disappears only 
 in an incomplete manner on pressure. In more severe cases veritable 
 cutaneous hemorrhages occur. They are sometimes more or less 
 extensive ecchymoses; at other times, well rounded and localized 
 spots. These characterize a special dermatological type — purpura — 
 which in some cases appears as an isolated manifestation, constitut- 
 ing infectious purpura, and in other instances as a symptom in the 
 course of a disease, such as measles, scarlatina, and especially variola. 
 
 Relationship Between Intensity of the Eruption and Gravity of 
 the Disease. Barring certain cases in which the eruption is incom- 
 plete, others in which the cutaneous manifestation seems to subside 
 rather too soon, for instance, when the eruption of measles disappears 
 on the appearance of a bronchopneumonia, it may be broadly 
 stated that the more profound the infection the more intense is the 
 exanthema, We do not say graver, since it is hardly possible to 
 establish a perfect equation between the intensity and the gravity 
 of a case. Variola alone is an exception to this rule. In this 
 infection prognosis is to be based upon the character of the eruption 
 
INFLUENCE OF INFECTIONS UPON THE 0BOANI8M. 
 
 rather than upon the general phenomena. We have often 
 hemorrhagic variola occur in patients whose tate, al our morning 
 visit, seemed to be excellent; there wa no high fever, delirium, or 
 marked pain; all that could be noted was a little toxic d] pnea. 
 A few hours later, dyspnea was inten ified, and before the end of the 
 day the patient was dead, retaining con ciou qi - to the la t. By 
 taking into serious accounl the eruption il ie possible to ma 
 prognosis which is always verified by the events, bul which astonishes 
 (hose who have never observed an epidemic of variola. 
 
 In the suppurative forms, likewise, the prognosis must be based 
 upon the intensity and course of the eruption. 
 
 It is customary to divide variolas into two varieties: true variolas 
 and varioloids, according as the pustule evolves or aborts. I' is 
 necessary to remark thai in varioloid the eruption does undergo 
 pustulation. While, however, in variola the pustule ruptures, and 
 an outward suppuration is produced, attended by secondary fever, 
 in varioloid the pustules remain closed. These dry and are covered 
 with a brown crust; but since they do not run a course of complete 
 evolution, the fever of suppuration is tacking. 
 
 According to the intensity of the eruption, true variola i- -aid to 
 be discrete, coherent, or confluent. The elements of eruption may 
 be confluent from the first, or may later become so by fusion and 
 growth. As, however, the intensity of the eruption varies according 
 to the territories observed, it has been agreed that the epithet must 
 be applied according to the state of the eruption upon the face. 
 At all events, the eruption is generally abundant upon the face: 
 only those cases in which a previous irritation has made another 
 part of the skin the point of attraction must be excepted. 
 
 It is necessary to consider the condition of both the skin and of the 
 mucous membranes. A profuse eruption in the throat, by embar- 
 rassing deglutition, hinders alimentation and greatly aggravates 
 prognosis. Not only the number but the evolution of the lesi< ins is 
 also to be taken into account. If the pustules, even though very 
 numerous, remain well separated and. as a result of the swelling of 
 the skin, do not become confluent, recovery is probable. Not infre- 
 quently these pustules are filled with a yellowish fluid, grow and 
 assume an acne-like aspect : this is also a favorable symptom. < >n 
 the other hand, when there is no edematous swelling in the face and 
 hands, when the pustules touch each other, and particularly when 
 they fuse, the prognosis is bad. 
 
436 
 
 INFECTIO US DISEASES. 
 
 At a later stage of the evolution, if the crusts developing upon the 
 pustule are unctuous and yellow, prognosis is favorable. If, on the 
 contrary, the crusts become dry and blackish, prognosis is almost 
 fatal. It is to.be noted in certain cases, even of true variola, that 
 some pustules abort; they are prematurely covered by a blackish 
 crust. The latter appearance assumed by certain isolated pustules 
 should not be confounded with the black desiccation of the confluent 
 elements, for premature desiccation is of good prognosis ; it indicates 
 that the organism is capable of struggling, since it is rapidly victorious 
 at certain points. Lastly, though even secondary hemorrhages 
 aggravate prognosis, it is well to remark that sanguinolent effusions 
 
 Fig. 33. 
 
 Post-erysipelatous pachydermia. 
 
 occurring tardily in certain pustules, notably in those of the hands 
 and feet, are compatible with a favorable prognosis. 
 
 Consequences of Cutaneous Infections. According to the nature 
 of the process, the cutaneous manifestations hitherto described may 
 disappear without leaving any traces, or may be followed by cicatrices. 
 Erythemata, exudative inflammations, even when they have dis- 
 turbed the cutaneous nutrition to the extent of producing abundant 
 desquamation, are completely cured. When, however, even simple 
 edematous forms of dermatites are repeated, a certain degree of 
 pachydermia may be a sequel. This occurs especially after ery- 
 sipelas. In some cases the lobule of the ear, in others the face, 
 
INFLUHNdU OF INFECTIONS UPON '/'///: ORGANISM. |.;7 
 
 remains thickened. In the case of a little girl of ten yean (Fig. 33), 
 who had several attacks of erysipelas in three years, developed | 
 erysipelatous pachydermia of the face. A may I"- seen in the 
 figure, her cheeks remained swollen, the upper lip protruding, and 
 
 the eyelids were so deeply infiltrated a i" partially cover the 
 balls. The visage had, however, retained all h- mobility and the 
 child ;ill her intelligence. This morbid state could, therefore, readily 
 
 be distinguished from pachydermia resulting from thyroideal in- 
 competency. 
 
 Without dwelling upon the vesiculobulbar infections and suppu- 
 rative and gangrenous lesions which are almosl invariably folk 
 by cicatrices, I shall only remark thai , while the eruption- of herpes 
 evolve without, leaving any (races, the eruption- of herpes ZOStei 
 terminate in cicatrices remarkable tor their pigmentation and the 
 sensory disorders surrounding them. 
 
 Clinical observation seems to demonstrate thai the i>>"ceous 
 glands are particularly involved in variola. The cicatrice- are 
 especially abundant and deep where these glands are most pro- 
 fusely distributed, namely, upon the forehead and nose. In some 
 patients convalescent from grave variola we have noticed the 
 persistence of whitish-yellow productions after the crusts had 
 dropped off, which are nothing else than altered sebaceous products, 
 at times simulating pustules. They may last for two or three 
 months. 
 
 The Sudoral Secretion. Vasomotor modifications may properly 
 be distinguished from secretory changes on the ground that while 
 cutaneous congestion certainly favors perspiration, diaphoresis may 
 often be observed in conditions of vasoconstriction; the expression 
 "cold perspiration" well indicates this peculiar state. 
 
 Certain infections have the property of diminishing considerably 
 the sweat secretion. The skin becomes dry, as is the case in scar- 
 latina and in most of the grave infections. The return of moisture 
 is a prognostic sign of importance. On the other hand, there are 
 some infections diseases attended by such profuse sweating as to 
 constitute a source of particular discomfort for the patient. The 
 t} r pe of such infections is represented by sudor anglicus, the sufferers 
 from which seem to be plunged in a vapor bath. The same is 
 observed, though to a less degree, in acute articular rheumatism. 
 There are also certain diseases in which the sweating occurs, not 
 during the entire course, as in the preceding examples, but at a 
 
438 IXFECTIO US DISEASES. 
 
 certain moment of the evolution of the disease. Malarial as well 
 as symptomatic intermit tent fevers present a stage of sweating at 
 the end of each paroxysm. Such is the case in paroxysms due to 
 deep-seated suppurations and pyemic conditions. 
 
 Sweating may become manifest at certain moments in the course 
 of typhoid fever; in general, however, patients do not complain 
 much of perspiration. Along with the habitual form of typhoid 
 may be placed a sudoral type, well described by Jaccoud — from the 
 very beginning sudoral paroxysms are observed, which recur during 
 the entire course of the disease, and at times persist during con- 
 valescence. 
 
 Perspiration is quite copious in measles and discrete variola, but 
 is absent in grave cases of the latter infection. Finally, copious 
 sweating is frequent in tuberculosis, in which disease it often appears 
 from the beginning of the infection, and presents the peculiar char- 
 acter of being produced during the night, or, more exactly, during 
 sleep and on awakening. It is generally localized to the chest, and 
 annoys the patient considerably; hence clinicians are now generally 
 agreed that it should be combated by means of antidiaphoretics. 
 
 Cold perspirations must not be overlooked. The skin is cold, 
 pale, sometimes bluish; certain regions, notably the forehead and 
 the hands, are covered with a viscid perspiration. This state is 
 observed in cases of collapse, asphyxia, and in the agonal stage of 
 all infections. It is marked in choleric patients succumbing in 
 collapse as well as in diphtheritica suffocating by reason of a laryn- 
 geal pseudomembrane. 
 
 We have too little information as to the chemical constitution of 
 sweat in the course of diseases to know whether it serves to eliminate 
 toxic principles. Such, however, seems to be the fact in the light 
 of investigations pursued by Arloing, Charrin, and Mavrojannis 
 concerning the toxicity of this secretion. It is further known that 
 perspiration may serve to eliminate bacteria ; in the course of septi- 
 cemias and pyemias sweat glands have more than once been found 
 capable of excreting the staphylococcus aureus. 
 
 The Muscular System in Infections. 
 
 Typhoid fever is the only disease in which the anatomical modi- 
 fications undergone by muscles in infections have been studied. 
 The muscles of individuals dead from typhoid are dark red, and 
 look dry and bloodless on section. Three varieties of degeneration 
 
INFLUENCE OF INFECTIONS UPON THE ORG INI H !.;:• 
 
 are detected under the microscope: granular, waxy, and vacuolar, 
 which involve only the contractile ub tance, while the nuclei and 
 protoplasm surrounding the latter proliferate. Alongside the degen- 
 erated fibres, however, there are found other* manifesting cellular 
 regression well described by KrSsnig and by Durante. Tin- i a 
 return of the fibre to its embryonic tate. Thi modification will 
 probably be found in all infections, and will confirm with reference 
 to the muscular tissue the law of rejuvenation of the organism, 
 which has already explained many other modifications occurring in 
 the course of the mosl varied infections. 
 
 The muscular alterations account for the occurrence of partial 
 ruptures and the production of hemorrhagic foci and even muscular 
 abscesses. II is known, however, thai suppurative myositis i 
 incident of very rare occurrence. 
 
 Action of the Colon Bacillus Toxins Upon Muscular Contractility. 
 It would be interesting to inquire as to functional modifications 
 occurring in the course of infections and first to determine the 
 influence exerted by microbic toxins. My researches on the -■ 
 tions of the colon bacillus elucidated the action of toxins upon the 
 nerve centres as well as upon the muscular tissue. 1 It will be re- 
 membered that the colon bacillus toxin when injected into ; _ 
 produces a poisoning which may be described as follows: first. 
 initial paresis; then, convulsions, and finally, terminal paralysis. 
 Muscular excitability is not modified or is slightly increased < luring 
 the first period. At the end of the second period important modi- 
 fications are observed: when a series of excitations are caused either 
 by acting directly upon the muscle or through reflex action — i. e.. 
 by applying the electrodes at more or less distant points of the 
 organism, relaxations follow contractions with remarkable slow: ss, 
 so that these contractions very closely approach a state of tetanus. 
 This may readily be seen by comparing the lines of Fig. 34. The 
 first line represents the normal contractility of the muscle under 
 the influence of a faradic current, the others represent the modi- 
 fications under the influence of toxins administered. These lines 
 are analogous to those given by fatigued muscles. These experi- 
 ments show that the colon bacillus secretes in bouillon a pois 
 capable of affecting the spinal cord and the muscli — . the 
 muscular tissue itself or the terminations of the motor nerve. 
 
 1 Roger. Etude sur la toxicity des produits solubles du Bacillus eoli communis. 
 Archives de physiologic. 1893. 
 
440 
 
 IXFECTIOUS DISEASES. 
 
 The foregoing facts have been confirmed by Charrin and Miss 
 Pompilian. 1 These authors, experimenting with the pyogenic and 
 
 Fig. 34. 
 
 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I I 1 1 
 
 ^rrmm-^^^^^t■^m^^^^^^^^^^^h , - 
 
 I I H i 1 i ' 
 
 Sj- 
 
 " 1 I I I L 
 
 Contractility of the normal (A) and of the poisoned muscle (B and C). 
 
 diphtheritic toxins, observed modifications in contraction resembling 
 those produced by fatigue. 
 
 Infectious Osteopathies and Arthropathies. 
 
 The considerations which we have presented in reference to 
 modifications of the bone-marrow in the course of infections explain 
 the development of certain disturbances and pains in the limbs or 
 in the epiphyses of the joints, and account for the rapid growth 
 often observed in young subjects during convalescence. It may 
 likewise be asked whether the lesions occurring in the course of 
 
 1 Charrin and Mile. Pompilian. Influence des toxines microbiennes sur la contrac- 
 tion musculaire. Soc. de biologie, November 28, 1896. 
 
INFLUENCE OF INFECTIONS UPON THE ORGANISM \\\ 
 
 gastrointestinal disorders play a rdle in the production ol certain 
 lesions in youth, notably rachitism. 
 
 Dr. Poncet has recently called attention to a tubercular pseudo- 
 rheumatism which presents characters similar to those of true 
 rheumatism. A few years Bince I observed a case of thk kind. I 
 was called to sec a young girl, sixteen years of age, who had Buffered 
 for five or six days from violent pain in the tibiotarsal joints. The 
 case had been diagnosed as acute articular rheumatism. In fact, 
 I round the affected joints swollen, the skin white and slightly 
 edematous, and movement almosl impossible. On a close] 
 animation I learned that the patienl had emaciated, and Ewasstruck 
 by her facies, pallor and dyspnea. On examining the thor; 
 found a, serous pleurisy which had insidiously developed. Then, 
 remembering Unit the sister of Km |>:iticn1 had died from acute 
 miliary tuberculosis two years before, I attributed nil the presenl 
 symptoms to tuberculosis. As a matter of fact, the articular affec- 
 tion was cured in a week, the pleuritic exudate was more slowly 
 absorbed, but at the same time pulmonary lesions developed, ending 
 fatally four months later. It is, therefore, well to remember that 
 temporary tubercular fluxions comparable to certain pleurisies and 
 slow types of hydrarthroses and white tumors may occur in the 
 articulations. 
 
 Among acute infections most frequently attended by articular 
 symptoms scarlatina occupies an important position. Few pati- 
 at least among adults, escape this quite painful but not grave com- 
 plication. A day or two after the eruption, patients complain of 
 difficulty of moving the fingers, and it may be seen that the joints 
 of the phalanges are swollen and painful. The wrist-joint is also 
 frequently involved, but the larger joints are rarely, if ever, affected. 
 It is well to add that these arthropathies are far more frequently 
 observed in women than in men, and are at times accompanied by 
 muscular pain and hj-peresthesia. In some instances these com- 
 plications appear during convalescence, and then present a very 
 different localization: they affect especially the knee-joint and then 
 the shoulders. Whether early or tardy, these arthropathies behave 
 like those of true rheumatism: they do not suppurate. 
 
 In measles arthropathies are rare : and the same is true as regards 
 variola. In the latter disease the affected joint may suppurate, and 
 its history is the same as that of multiple suppurations produced 
 bv this disease. 
 
CHAPTER XV. 
 
 INFLUENCE OF INFECTIONS UPON THE VARIOUS PARTS 
 OF THE ORGANISM (Continued). 
 
 Influence of Infections upon the Circulator}'' Apparatus. Functional Disorders of the 
 Heart. Modifications in the Pulse During Convalescence. The Non-organic Mur- 
 murs. The Action of Microbic Toxins upon the Heart and Blood Pressure. Infec- 
 tious Myocardites, Endocardites, and Pericardites. Cardiac Hypertrophies in Rap- 
 idly Growing Young Subjects. Action of Infections upon the Arteries. Role of 
 Infections in the Development of Arteriosclerosis. Action of Infections upon the 
 Respiratory Apparatus. The Lungs in Infectious Diseases. Classification of Pul- 
 monary Lesions of Infectious Diseases. Pleural Lesions in Infections. Serous 
 Pleurisies. Purulent Pleurisies. Hemorrhagic Pleurisies. Tracheobronchial Aden- 
 opathies. Remote Consequences of Infections of the Respiratory Apparatus. 
 
 Influence of Infections upon the Circulatory Apparatus. 
 
 Functional Disorders of the Heart. The action of infections upon 
 the heart may be expressed by two kinds of phenomena — functional 
 disturbances, and lesions. The high temperature may be held 
 responsible for the functional disorders. In fact, when the bodily 
 temperature rises, no matter by what procedure, the pulse is accel- 
 erated. The increased activity of combustion evidently results in 
 acceleration of the respiratory movements and cardiac pulsations; 
 in this manner elimination of the waste products resulting from the 
 exaggerated organic combustion is assured. 
 
 Hyperthermia, however, does not represent the onty factor 
 accountable for the accelerated heart beats, since, if such were the 
 case, the pulsations should always present the same frequency at 
 the same temperature. It is true that, in adults, each degree 
 centigrade of thermal rise admittedly corresponds to an increase of 
 ten pulsations. For instance, if the temperature rises to 105.8° F. 
 (41° C), the pulse rises from 80 to 120. Such is not always the case, 
 however. Certain fevers induce greater acceleration of heart beats 
 than others. For instance, in scarlatina the pulse is far more rapid 
 for the same degree of temperature than in other infections. It is> 
 therefore, probable that toxins directly or indirectly influence the 
 movements of the heart. It is, moreover, known that an unusual 
 acceleration in the heart beats in the course of an infection suggests 
 
TNFLUENOE OF INFECTIONS UPON THE OBOA / If. | }.; 
 
 some complication paralysis of the nerve centre . myocardil 
 viscera] lesion, a profuse hemorrhage, and, in typhoid fever, an 
 Intestinal perforation. 
 
 During convalescence a subnormal temperature often coinci 
 with a pulse less rapid than normal. Some patients, e pecially 
 children, may present ;ii this time an irregular pnl e. To the un- 
 informed physician this functional disorder maj a myocardial 
 involvement. During the stationary period cardiac irregularities 
 are of more serious significance, and should draw the physician's 
 attention to the condition of the myocardium. It is to be noted, 
 however, that in cases of erysipelas with normal temperature or ;i 
 temperature slightly above normal, whether the pulse is slow or 
 rapid, marked irregularities in the cardiac movements may occur 
 at all ages and even in very benign cases, Irregularity and inter- 
 mittence of the heart beats may also be observed in cases of scar- 
 latina; and, though they are particularly frequent during con- 
 valescence, they may likewise be met with during the stationary 
 period. 
 
 The absence of symptoms ascribable to a myocardial lesion leads 
 to the admission that these various manifestations depend simply 
 upon nervous influence. 
 
 Non-organic Murmurs. Murmurs presenting all the characters 
 of extracardiac murmurs described by Potain are very frequently 
 heard in the most varied infections. These murmurs are not rough ; 
 they are mesosystolic, exceptionally mesodiastolic. Their intensity 
 varies from one moment to another; the} r diminish or disappear in 
 the sitting posture, and remain localized at the points at which they 
 originate. The}^ are usually observed in scarlatina, and are more 
 frequent in women than in men. These murmurs are of rarer occur- 
 rence in children ; they nevertheless occur, and may be heard even 
 in young subjects five or six years of age. Their frequency in 
 scarlatina is about 22 per cent. 
 
 The murmurs of typhoid fever possess the particular character 
 of being pre-infundibular ; they appear as early as the end of the 
 first week, which indicates that they depend, not upon post-infectious 
 anemia, but upon the fever itself. Potain attributed them to febrile 
 excitation of the heart. They are. perhaps, connected with a slight 
 degree of myocarditis and, at times, aortitis. In support of this 
 view I must remark that, in certain instances, the extracardiac 
 murmur suddenly gives place to a diastolic '"bruit de galop " con- 
 
444 1SFECTI0 US DISEASES. 
 
 nected with myocarditis. The excited state of the myocardium 
 explains the first phenomenon; the loss of tonicity, supervening 
 later, accounts for the "bruit de galop.'"' 
 
 Action of Toxins Upon the Heart and Blood Pressure. Manfredi 
 and Traversa, experimenting upon frogs, demonstrated that the 
 soluble products of the streptococcus notably slow the movements of 
 the heart. Gley and Charrin observed the same effects with sterilized 
 cultures of the bacillus pyocyaneus; they moreover obtained cardiac 
 dilatation in mammals. The latter manifestation is of considerable 
 importance, since it tends to indicate that the extracardiac murmurs 
 above described may be clue to a slight degree of dilatation of the 
 heart. I also undertook to study the action of the various toxins 
 upon the frog's heart. 1 The most interesting results were obtained 
 by means of sterilized cultures of the bacillus septicus puditus. 
 These cultures, when injected beneath the skin of a frog, produce 
 marked paresis within fifteen or twenty minutes, excitations never- 
 theless give rise to reflex movements, and the animal at times jumps. 
 If, however, under these conditions, the thorax is opened and the 
 heart exposed, this organ is found to be beating very slowly or at 
 a standstill. This arrest of the heart occurs, therefore, at an early 
 period of intoxication, while the other morbid manifestations have 
 not yet become grave. 
 
 This study was recently taken up by Drs. Chantemesse and Lamy 2 
 who experimented upon the hearts of tortoises by means of ex- 
 tremely ingenious contrivances. They demonstrated that the 
 typhoid and the diphtheritic toxins are poisons for the myocardium 
 and produce cardiac paralysis after a period of latency. Of still 
 greater interest is the fact that the blood of an animal which has 
 received one or the other of these toxins, exerts an exciting action 
 upon the heart, which action seems to be due to a new substance 
 elaborated by the organism under the influence of the microbic 
 poison. 
 
 These cardiac disorders, however, do not seem to be entirely due 
 to the action of microbic poisons upon the heart ; certain manifesta- 
 tions are probably caused by an influence exerted upon the peripheral 
 
 1 Roger. Poison cardiaque d'origine microbienne. Soci^te 1 de biologie, Jan. 28, 1S93; 
 Archives de physiologie, April, 1893. Action de quelques toxines microbiennes sur le 
 cceur. Society de biologie, Feb. 18, 1893. Etude sur la toxicite des produits solubles 
 du Bacillus coli communis. Archives de physiologie, July, 1893. 
 
 2 Chantemesse and Lamy. Effets des toxines microbiennes sur le cceur isol6. XIII 
 Medical Congress, section of general pathology, 1901, p. 137. 
 
INFLUENCE OF INFECTIONS UPON THE ORG I / If | ;:, 
 
 circulation. I'ouclnu-il, Charrin, Gamaleia, ( Hey, and Arloing 
 dwelt upon the vasomotor modification* produced by to: 
 The author studied fche influence of poison secreted by the colon 
 bacillus of dysentery. 1 This microbe hat the advantage of furnish- 
 ing exceedingly toxic cultures. These cultures, when sterilized by 
 means of chloroform and injected into rabbits in the proportion of 
 ().2f) per kilogram of animal, cause death wil bin i wenty-four or forty- 
 eight hours. The author studied, by the graphic method, the el 
 produced upon (he ciivulaiion :ind respiration. The poison evidently 
 I ended to lower the blood pressure. A i ;i certain moment, when the 
 pressure is considerably reduced, convulsions occur which raise the 
 pressure, and slight improvement takes place. The morbid symp- 
 toms are soon intensified, the blood pressure continues to fall, the 
 descending course being marked by renewed convulsions. Lastly, 
 a rapid and final reduction in pressure occurs, and the animal dies. 
 
 These experiments show that the heart struggles against the in- 
 fluence of the toxin. Its contractions become more energetic and 
 slower. The poison does not, therefore, act upon the heart, and the 
 reduced pressure is probably due to modifications in the abdominal 
 circulation. Intense congestion in the intestine, liver, and kidneys 
 revealed by the necropsy seems to support this view. 
 
 Unlike the circulation, respiration is but slightly disturl >ed. When 
 2.5 c.mm. of the cultures are injected into the veins the respiratory 
 movements generally do not present any modification. At most 
 they may be slightly accelerated for a few seconds. With the 
 employment of doses twice or three times larger the movements 
 become 136 per minute, instead of 80; the amplitude is coincidently 
 diminished by one-third. These manifestations are transitory, how- 
 ever, and do not last more than fifteen or twenty seconds. At a 
 more advanced stage of intoxication breathing is again acceler- 
 ated (Fig. 35); it is then slowed. Long pauses are observed: only 
 twenty or even ten inspirations per minute occur. The animal thus 
 succumbs by arrest of respiration while the heart is still beating. 
 
 Comparison of these experimental phenomena with certain clinical 
 manifestations reveals an analogy — that is. lowering in the blood 
 pressure. The latter disturbance has often been attributed to diar- 
 rhea, which produces dehydration of the organism. Contrary to this 
 
 1 Roger. Les toxines du colibacille de la dysenteric Annales de la Soc. de m£d. de 
 Gand, April, 1900, p. 139. Action des toxines de colibacille de la dysenteric sur la 
 circulation et la respiration. Presse mod.. Nov. 3. 1900. 
 
446 ISFECTIO US DISEASES. 
 
 view, I conclude from experimental results that it is due to intoxi- 
 cation, since the toxins do not decidedly affect the myocardium. 
 "We now likewise understand why the pressure quickly rises as soon 
 as gastrointestinal intoxication is checked or an intravenous injection 
 of artificial serum is given to remedy the effects of peripheral vaso- 
 dilatation. Finally, our experimental results offer a new illustration 
 of the compensating antagonism existing between the peripheral 
 and central circulation. By the increased energy of its contractions 
 the heart endeavors to raise the blood pressure, which tends to fall 
 as a result of abdominal vasodilatation. 
 
 Fig. 35. 
 
 Rapid and short respiration. Slow and energetic cardiac movements. The lower line 
 indicates the struggle of the heart against the lowering of blood pressure. The upper 
 line represents the respiration. 
 
 Acute Myocardites. Acute myocardites may be primary, but 
 they generally develop in the course of an infectious disease. As 
 is the case in other visceropathies, localization in the myocardium 
 is favored by various auxiliary causes. Among these, the influence 
 of age is one of the most important. The affection is commonly 
 observed between the ages of ten and thirty years, because at this 
 period of life the infectious diseases capable of engendering it are 
 frequent. Heredity also plays a role; Benecke found in a total of 
 twenty-eight cases twenty-two presenting evidences of congenital 
 debility of the circulatory system. Overexertion has long been con- 
 sidered among the causes of acute, diffuse or circumscribed myo- 
 cardites. Army physicians have often noted the frequent appear- 
 ance of myocarditis in consequence of forced marches. It is at 
 
INFLUENCE OF INFECTIONS UPON THE ORG I / M. 117 
 
 present established thai overexertion does nol create alteration of 
 the myocardium; it simply acts by lessening th< re i tance of the 
 organism, and thus favors ii.s contamination by infectiou germs. 
 The latter become localized in the heart,which, a a re ul1 of it- 
 excessive activity, is found in a state of morbid receptivil 
 
 All infections, including acute articular rheumatism, are capable 
 of giving rise to acute myocarditis. Typhoid stands al the head of 
 the list; all of its forms, however, do nol equally predispose the 
 sufferer to this cardiac involvement. The ataxo-adynamic form 
 with hyperthermia is |»;ir!icnl:irly ap1 to induce alteration of the 
 myocardium. ( )ut of 152 necropsies, Hoffmann found bul 54 hearts 
 almost sound. In the course of the third week myocarditis almost 
 constantly makes its appearance. Myocarditis also appears early, 
 at times on the fifth day in grave confluent cases of variola. Accord- 
 ing to Desnos and Huchard most deaths occurring befon- the eleventh 
 day of this disease must be attributed to myocarditis. 
 
 Pneumonia, is often complicated by myocarditis. Only a few- 
 years ago French physicians received with astonishment. Jurgensen'a 
 work, which laid much stress upon pneumonia myocarditis. At 
 present pneumonia is found modified; its course is tedious, defer- 
 vescence is tardy, and fatal termination is more frequent. We are 
 now observing in France what Jurgensen observed in Germany a 
 few years ago: myocarditis has become one of the frequent ci 
 of death in pneumonia. 
 
 Streptococcic infections may also be complicated by myocarditis 
 This involvement is rare in erysipelas, but frequent in puerperal and 
 surgical septicemias, and may occur even in streptococcic - 
 throats. Myocarditis is also encountered in scarlatina, typhus fever, 
 intermittent fever, and acute tuberculosis. In chronic tuberculosis 
 it seems to depend upon secondary infections. In measles it is 
 altogether exceptional. Myocarditis is of very frequent occurrence 
 in diphtheria, and it is often expressed by symptoms difficult of 
 interpretation. 
 
 The symptomatology of acute myocarditis is divided by authors 
 into two phases: one of erethism, and another of depression. In 
 the former stage the heart beats more frequently and strongly. 
 The patient complains of palpitation and precordial or sternal pain 
 Pain may also be caused by pressing the finger upon the third or 
 fourth intercostal space on the left side, the point which Peter 
 called "the precordial button** (le bouton precordial). These dis- 
 
448 IXFECTIO US DISEASES. 
 
 turbances soon bring in their train pulmonary manifestations, 
 notably intense dyspnea. After three or four days the second phase 
 of myocarditis appears. The heart -beats become weak and rapid, 
 growing gradually inappreciable by palpation. On percussion pre- 
 cordial flatness is found to be increased, owing to dilatation of the 
 heart. Auscultation reveals a "bruit de galop," due to ventricular 
 ectasis or a very soft mesosystolic or even systolic murmur at the 
 apex. This may be due to functional incompetence of the auriculo- 
 ventricular valves as w^ell as to dilatation of the heart; hence the 
 disappearance of the murmur wiien a movement of the patient 
 increases the power of the contractions by arousing the energy of 
 the myocardium. These phenomena are soon replaced by the 
 fetal rhythm of Stokes or embryocardia of Huchard. The tw r o 
 murmurs of the heart are rapid and w r eak and can no longer be 
 distinguished. They succeed each other after the manner of the 
 tick-tack of a clock. Later, when the first murmur becomes so w 7 eak 
 as to indicate an incomplete systole, and the second murmur also, 
 in its turn, further diminishes, a fatal termination, according to 
 Bucquoy, may be expected within a day or two. The pulse presents 
 modifications corresponding to those of the heart. It is unequal 
 rather than irregular. It manifests veritable intermittence only 
 toward the end of the disease. 
 
 The period of excitation is lacking in typhoid fever. Myocarditis 
 may even remain in a state of latency and be expressed simply by 
 acceleration and weakness of the heart-beats; hence the occurrence 
 of sudden death on the occasion of movement. 
 
 Differential diagnosis between myocarditis and endocarditis or 
 pericarditis may sometimes be difficult; an error is more liable to 
 occur as these various lesions may coexist. Modifications in the 
 pulse must first be taken into consideration; and then it must be 
 remembered that the murmur of endocarditis increases on move- 
 ment and under the influence of any cause rendering the heart-beats 
 more energetic. The reverse is the case in myocarditis. Moreover, 
 the murmur of myocarditis is transitory. No doubt remains, how- 
 ever, as to the myocarditic nature of the events when the ' ( bruit de 
 galop" and especially the fetal rhythm are found. 
 
 Post-infectious Cardiac Hypertrophy. I believe that a previous 
 infection is ver} r often responsible for the cardiac hypertrophy of 
 young subjects which is too readily attributed to rapid growth. 
 There are two possible events. In some cases the development of a 
 
influence OF INFECTIONS UPON THE ORGANISM. ) \'j 
 
 lesion, such as endocarditis, is observed in the course of b di 
 At this age (his lesion is curable, and a1 the end of o few montt 
 a year or two at the latest, h is repaired. The subjeel retainc a 
 hypertrophy of the heart, however, which causes shortness of breath 
 and troublesome palpitations of the heaii totheextenl of rendering 
 walking, bodily, and even intellectual exertion, difficult. If the 
 physician has followed the entire evolution, he attributes this hyper- 
 trophy to the valvular lesion, and considers the case one of compen- 
 sating hypertrophy, somewhal exceeding the requirement* of the 
 •organism and surviving (lie causative lesion. In other instances 
 the heart does not seem to have been affected during the die* 
 no lesion of the myocardium has been expressed by the slightesl 
 murmur. Hypertrophy, nevertheless, develops, and when the 
 patient complains of it and it is discovered, the physician hesitates 
 to connect the apparently recent disorder with the disease of years 
 ago. I believe, however, the mechanism to be the same in both 
 instances. Infection, whether having affected the valvular endo- 
 cardium or not, has produced lesions in the myocardium. Compen- 
 satory hypertrophy is designed to re-establish the disturbed cir- 
 culatory mechanism; the effort, however, exceeds the end and 
 terminates in a veritable lesion. Such is, in my opinion, the cause 
 of a great number of hypertrophies attributed to rapid growth and 
 occurring after the most varied diseases, among which typhoid fever, 
 acute articular rheumatism, scarlatina, and diphtheria may particu- 
 larly be mentioned. 
 
 Although these hypertrophies are at times quite troublesome, 
 they are not alwa} r s grave. The heart which is hypertrophied may 
 ,soon cease to develop; the individual continues to grow, the chest 
 develops, and there comes a time when the heart appears to have 
 resumed a normal volume and regular activity. Only a long period 
 ■of time after, at the end of twenty or thirty years, new disorders 
 become manifest — i. e., signs of chronic myocarditis, at times accom- 
 panied by valvular endocarditis, which is developed in an insidious 
 manner. 
 
 Endocarditis. It is at present well established that every acute 
 endocarditis is of infectious origin and that all infections are capable 
 of involving the endocardium. Endocarditis may be benign or 
 malignant and ulcerative. These differences depend in part upon 
 the nature and virulent potency of the microbe. The state of the 
 attacked organism, however, is of greater importance. Endo- 
 
 29 
 
450 INFECTIO US DISEASES. 
 
 carditis assumes the ulcerative character when the individual is 
 already debilitated by previous or present disease, overexertion, and 
 evil hygienic conditions, abortion, the puerperal state, or previous 
 lesions, which Netter has found in 50 per cent, and Goodhart in 
 75 per cent, of the cases. 
 
 The frequency of endocarditis in rheumatism was well demon- 
 strated by Bouilland. It may be stated that endocarditis is the 
 rule in grave acute, generalized rheumatism; it is exceptional in 
 apyretic, slight, and partial rheumatism. The employment of salicy- 
 lates, however, seems to diminish the cardiac complication by arrest- 
 ing the evolution of the disease. Endocarditis, nevertheless makes 
 its appearance in one-fourth of the cases in adults. In children, 
 according to Cadet de Gassicourt, it is observed in the proportion 
 of 80 per cent. The first symptoms of the cardiac involvement 
 are generally manifested at the end of the first or in the course of 
 the second week. The lesion occupies the mitral, less frequently 
 the aortic, valves, and exceptionally the right heart. 
 
 Other infections may engender a vegetative or an ulcerative endo- 
 carditis. It is admitted that the lesion of the heart is at times due 
 to the action of the principal agent, but in a greater number of 
 instances it must be attributed to secondary infection. Endo- 
 carditis occurring in influenza, gonorrhea, and tuberculosis results 
 from secondary infection by the streptococcus, pneumococcus, and 
 less often the staphylococcus. It is well to remember, however, that 
 Koch's bacillus may be localized in the endocardium, especially in 
 cases of acute tuberculosis. Contrary to what might be expected, 
 endocarditis is very rare in erysipelas; the microbe exhausts its 
 power in the skin and manifests no tendency to invade the viscera. 
 The frequency of endocarditis in pneumonia has of late been demon- 
 strated by numerous observations. Sometimes the streptococcus, 
 but most frequently the pneumococcus, is the responsible agent. 
 The cardiac complication may occur in the decline of the pulmonary 
 infection or after defervescence. The aortic orifice is generally the 
 point of attack, and the process is, as a rule, ulcerative. Ulcerative 
 endocarditis is also encountered in 37 per cent, of the cases of 
 pyemias and in 11 per cent, of puerperal septicemias. Articular 
 manifestations often accompany the process and give it the appear- 
 ance of infectious pseuclorheumatism. 
 
 The vegetative or warty type develops in an insidious manner. 
 Some phenomena, such as precordial pain, palpitation on the slightest 
 
INFLUENCE OP INFECTIONS UPON THE ORGANISM. \:,\ 
 
 exertion, embarrassed respiration, cephalalgi i i the \ 
 
 bility of cardiac localization. All these manife tations, how 
 are inconstant. Endocarditis, may therefore, readily escape notice 
 if the heart is not systematically examined. A.1 the beginning of 
 valvulitis the phenomena are those or cardiac excitation; there is 
 as yet no murmur, since al this time the valve ft, thickened, 
 
 ;ui(l incapable of vibration by the blood waves. The normal 
 murmurs are round to be rather dull; the firsl especially becomes 
 indistinct at the apex the swollen valves -till insure occlusion, bul 
 no longer snap. When the aorta \& the affected pari the second 
 murmur is found dull a1 the base. Only a1 a later period do the 
 murmurs of incompetency become manifest. 
 
 The ulcerative form may also escape attention, bul for different 
 reasons — the physician's al trillion is absorbed by the severity of 
 the general phenomena. In view of these, two principal clinical 
 forms haA^e been described: a typhoid form and a pyemic form 
 In the former case the pneumococcus is the habitual agent. Either 
 at the beginning or four to six days after defervescence of a pneu- 
 monia the patient experiences a single chill and rapidly develops 
 fever at 10-1° or 105.8° F. (40° or 41° C). The cardiac pulsations 
 are painful and frequent; the pulse is small and often irregular. 
 Adynamia makes rapid progress. In some cases embolism occur.-, 
 giving rise to sudden hemiplegia, exceptionally to paraplegia, at 
 which time all doubt as to the diagnosis is dispelled. In the pyemic 
 form the dominant feature is the enormous oscillations of the fever, 
 which occurs in the form of paroxysms, characterized by the three 
 classical stages — chill, fever, and sweating. This is Lancereaux's 
 intermittent form. In this t3^pe embolism is far more frequent than 
 in the preceding. In the typhoid type the aortic orifice is generally 
 affected; in the pyemic, the mitral. 
 
 Ulcerative endocarditis is but exceptionally curable. On the 
 other hand, the warty form is often cured, and cured in a complete 
 manner. The happy termination sometimes occurs so rapidly as 
 to render the diagnosis doubtful. In a case of grave erysipelas I 
 heard a systolic murmur at the apex. Ulcerative endocarditis was 
 thought of, but the murmur diminished in four days and completely 
 disappeared within a week. This evolution is not rare when the 
 patients can be watched. I treated a little girl who suffered three 
 times from acute articular rheumatism. During the first attack, 
 which occurred at the age of four years, mitral incompetency was 
 
452 IXFECTIOUS DISEASES. 
 
 produced, which healed in eight months. She had a second attack 
 of rheumatism when seven years old, and developed the same 
 symptoms, which disappeared as rapidly as in the first instance. 
 At the age of fifteen years she had a third attack, and a systolic 
 murmur again made its appearance, and took eighteen months to 
 disappear. From that time on the heart remained hypertrophied ; 
 but this condition was later compensated by the mechanism already 
 indicated. At present this individual is nineteen years old, and the 
 heart seems to be absolutely normal. 
 
 Pericarditis. Pericarditis may represent the principal localization 
 of an at first generalized infectious process, or it may supevene as 
 a secondary phenomenon. It often coexists with endocarditis and 
 myocarditis ; such a pancarditis is the rule in children. As in the case 
 of endocarditis, bad hygienic conditions, fatigue, alcoholism, and cold 
 favor the localization in the heart. Thus is explained the occurrence 
 of epidemics of pericarditis formerly observed in besieged cities. 
 
 The pericardiac lesion often occurs under the influence of rheu- 
 matism. The eruptive fevers may also reach the pericardium. At 
 the eruptive period of variola dry pericarditis is said to develop; 
 later, purulent pericarditis is found. It is rare in measles, but quite 
 frequent in scarlatina. In the latter instance it is said to easily 
 become purulent or hemorrhagic in character, but my observations 
 do not confirm this statement. I have mainly found dry peri- 
 cardites. During the stationary period or in convalescence friction 
 murmur is heard, lasting for five or six days; it seldom persists for 
 two weeks. There may be no disturbance to draw the physician's 
 attention to the heart, or the patient may in some cases complain 
 of palpitation and precordial pains. The beginning of the process 
 may be marked by syncope. In the course of erysipelas I have 
 sometimes heard pericardial frictions which disappeared after causing 
 some pain, palpitation, and tachycardia. In two instances, however, 
 pericarditis caused a fatal termination. A woman, seventy-two 
 years old, suffering from a wandering erysipelas, died on the eleventh 
 day, and the necropsy revealed a purulent pericarditis and a slight 
 mitral valvulitis. Another woman, eighty-two years of age, also 
 suffering from an attack of wandering erysipelas, succumbed when 
 the cutaneous lesions were almost cured; at the necropsy a purulent 
 pericarditis was found. 
 
 Pericarditis is frequently observed in tuberculosis; 14 per cent, of 
 pericardites are connected with tuberculosis (Bamberger). 
 
INFLUENCE OF INFECTIONS UPON THE ORG i VI v. );,;; 
 
 In some cases pericarditis ii u hered in by chills, fever, dyspnea, 
 precordial pain, at timee by dysphagia. The temperature usually 
 rises, but in certain cases il may be lowered a1 the moment of this 
 complication, as occurs, for example, in typhoid fever (Charcot, 
 Brouardel). In the majority of cases pericarditis remains in a 
 of latency; daily examination i required in order to discover it. 
 h- must, therefore, be systematically looked for in the coin 
 diseases capable of causing this complication. 
 
 The nature of the effusion is of greal prognostic value, for it 
 indicates the degree of gravity of the causative pro© Prognosis 
 is favorable in cases of dry pericarditis; doubtful in cases with 
 effusion; xcvy grave in purulent, and fatal in hemorrhagic peri- 
 carditis. When the previous condition and age of the patient at 
 well as the etiological conditions and general Bymptoms are further 
 taken into consideration, all the elements required for a correct 
 appreciation of the case will be at hand. 
 
 Action of Infections upon the Arteries. 
 
 Acute arteritis is not, as was once believed, a generalized process 
 causing fever, but a localized affection resulting from fever. Its 
 etiology may be described by a single word — infection. The mosi 
 typical example is represented by arteritis of the limbs with con- 
 secutive gangrene occurring mainly in grave infections and nearly 
 always at their decline or during convalescence. 
 
 Typhoid is undoubtedly the infection most frequently concerned 
 in arteritis. This complication is usually observed in the lower 
 extremities on one side, oftener on the right than on the left, and 
 preferably in the posterior tibial, next the femoral, anterior tibial. 
 or dorsalis pedis artery : the arteries of the upper extremities an i less 
 frequently involved: the iliac, external carotid,'" Sylvian (Vulpian . 
 even the pulmonary (Hoffmann) artery. The arterioles of the 
 viscera are often affected during the stationary period, while arteritis 
 in the limbs seldom, if ever, appears before the third week, and 
 sometimes not until the forty-first (Rendu), or even fifty-eighth day 
 (Barie). 
 
 According to Leyden, influenza causes acute arteritis as often as 
 if not more frequently than typhoid fever does. In half of the cases 
 the popliteal is the seat of inflammation: next the femoral, humeral, 
 axillary, cerebral, and central artery of the retina. Here also the 
 complication occurs during convalescence. 
 
454 IXFECTIO US DISEASES. 
 
 Arteritis has been noticed in variola, especially in the hemorrhagic 
 form of it, sometimes as early as in the period of eruption, at other 
 times later, and, apart from the aorta, the coronary arteries are 
 usually attacked. Scarlatinal arteritis also localizes in the coroll- 
 aries, and is a complication of rare occurrence. In a total of 2213 
 cases observed in our wards of Porte d'Aubervilliers we found only 
 one instance of acute arteritis in scarlatina, and that was seated in 
 the femoral artery. In measles it has scarcely ever been observed. 
 It is not rare in diphtheria, and involves usually the coronary, 
 pulmonary, renal and Sylvian arteries. Erysipelas has been seen 
 to be complicated by inflammation of the circle of Willis (Ponfick), 
 obliteration of the nutrient arterioles of the eyeball (Parinaud), and 
 a thrombosis of the popliteal (Schmitt). Among other infections 
 we may cite puerperal fever, septicemias, pyemias, typhus, pneu- 
 monia, cholera, etc. I have observed cerebral arteritis with throm- 
 bosis and acute softening of the brain in the course of a gastro- 
 enteritis. Arteritis of the limbs was observed by Legroux in acute 
 articular rheumatism. Hanot believes that acute rheumatismal 
 arteritis often accompanies endocarditis, but remains unnoticed by 
 reason of the obscurity of its symptomatology. Leyden noted an 
 arteritis of the popliteal occurring in a suppurative appendicitis. 
 We may also mention the case of Haushalter concerning thrombosis 
 of the Sylvian and anterior cerebral arteries in a child suffering 
 from empyema, and the observation of Vaquez regarding a tuber- 
 cular subject. 
 
 To sum up, while inflammation of the visceral arterioles is of 
 frequent occurrence in infectious diseases, acute arteritis of the 
 extremities is exceptional outside typhoid fever and influenza. 
 
 Acute arterites may be due to a localization of the microbic agent 
 responsible for the principal disease ; in other cases they represent a 
 secondary infection; and in still a third class of instances toxins, 
 independently of figurate elements, seem to be capable of producing 
 inflammation in the vessels. 
 
 The microbes of typhoid fever, pneumonia, and erysipelas some- 
 times induce arteritis. On examining the myocardium in eight 
 typhoid cases Rattone found Eberth's bacillus in the walls of the 
 arterioles distributed to this muscle in seven instances. In almost 
 all cases in which the arteries of the extremities are affected, inflam- 
 mation is due to a superadded infection by the pneumococcus, more 
 frequently by the streptococcus. Finally, arteritis sometimes 
 
INFLUENCE OF TNFE0TI0N8 UPON THE ORGANISM. .\:,: t 
 
 develops under the influence of toxin . a i undoubtedly the ■ 
 in certain instances of diphtheritic arteritis. Experimental demon- 
 strations have Fully corroborated clinical observation on tl 
 points. 
 
 The first symptom of arteritis in the limbs is generally pain, 
 increasing during the night. Rise in the bodily temperature and 
 acceleration of the pulse also occur. Coincidently, or somewhat 
 later, torpor, heaviness, and formication are fell in the affected limb. 
 Pulsation in the diseased artery and its branches is a1 first weakened, 
 and subsequently disappears; ;i supplementary circulation, however, 
 is established which insures nulrilion of the parts^ In n. 
 the events proceed thus: the color of the skin in the diseased segment 
 becomes whitish, its temperature is lowered, and sensibility dimin- 
 ished; hence a characteristic contrast between the superficial hyper- 
 esthesia and painfulness in the deeper parts results. At a later stage 
 patches of cyanosis and even purpura make their appearance, firsl 
 at the end of the limb — i. e., lingers or toes, announcing the immi- 
 nence of sloughing. The latter condition, however, does not qi 
 sarily occur; a sufficient collateral circulation may tardily be effected, 
 and the limb then gradually resumes its normal characters. In 
 other instances, after a deceiving remission, the symptoms again 
 become aggravated, and the affection runs its course toward sphace- 
 lation. When gangrene is thus produced the danger is not confined 
 to the limb; the toxins originating in the dying tissues induce a 
 very grave general state. Fever, fetid diarrhea, dyspnea, delirium, 
 and a profound adynamia are some of the features of the general 
 condition, in which fatal termination sometimes occurs before the 
 separation of the eschar. 
 
 Role of Infections in the Development of Arteriosclerosis. The 
 study of acute arteritis raises a pathogenic problem of the highest 
 interest : What is the role of infection in the development of arterio- 
 sclerosis ? 
 
 In the first place, I think it is a well-demonstrated fact that 
 gastrointestinal disturbances when characterized by excessive 
 fermentations and putrefactions induce arterial changes. The 
 question is one of veritable intoxication of the organism, and. though 
 the liver is generally the organ most profoundly affected, the poisons 
 sooner or later pass the barrier opposed by this gland and exert 
 their action upon other parts of the organism, notably upon the 
 arteries and the main emunctorv. the kidnev. 
 
456 INFECTIOUS DISEASES. 
 
 The influence of temporary infections is not as simple as that of 
 intestinal putrefactions. Numerous clinical observations, however, 
 demonstrate the reality of this etiological factor. Gueneau de 
 Mussy claimed to have seen the arteries suffer a rapid fibrous trans- 
 formation in the course of an attack of rheumatism. Parrot noted 
 the development of infectious arteritis of the aorta in childhood, 
 discovering atheromatous points at the root of the coronary arteries. 
 Landouzy and Siredey have shown that arterial lesions are far more 
 extensive than was once believed, and terminate in arteriosclerosis. 
 It is true, however, that in the acute period arterial lesions pre- 
 dominate at certain points; the same is true as regards the chronic 
 forms. The arterial system is not affected throughout in the same 
 degree. 
 
 In this connection the influence of chrome diseases such as malaria, 
 syphilis, and tuberculosis is by no means less important. Here also 
 it is true that the lesions produced by syphilis are circumscribed; 
 hence Lancereaux and Heubner deny to this disease all influence 
 in the production of arteriosclerosis. I believe Cornil is right in 
 attributing to syphilis certain cases of atheroma occurring in young 
 subjects in the absence of any other appreciable cause. The in- 
 fluence of tuberculosis seems more certain. The experiments of 
 Vissman and of Therese demonstrated that intravenous injection of 
 dead bacilli or of tuberculin is followed by diffuse arterial alterations. 
 On the other hand, H. Martin and P. Teissier have pointed out the 
 hardness of the arteries in certain young tuberculous subjects in 
 spite of lowered blood pressure, which is the rule in tuberculosis. 
 
 Action of Infections upon the Respiratory Apparatus. 
 
 Larynx. The mucous membrane of the larynx may be the seat 
 of catarrhal manifestations expressing the principal or subordinate 
 localization of an infectious process. At present there is no doubt 
 as to the microbic origin of laryngites, which were usually attributed 
 to cold. The latter plays the role of an occasional cause. 
 
 Laryngitis is sometimes one of the manifestations of a general 
 infection. In measles the larynx, trachea, and bronchi participate 
 in the catarrhal process, which at the same time involves the mucous 
 membrane of the nose and eyelids. During the stationary period 
 of infections the larynx may be invaded by the morbid process. 
 This localization is generally of little importance, but in some cases 
 it may prove very serious. Thus in variola pustules may develop 
 
INFLUENCE OF INFECTIONS UPON THE ORG I / If. 457 
 
 in the larynx and induce edema of the glotti . The re ill 
 growing dyspnea necessitating surgical intervention. This hap- 
 pened in five of our patients, four of them i offering from confluent, 
 one from coherent variola. In spite of tracheotomy, these five 
 individuals, who were profoundly infected, diedi Even varicella, 
 which is generally a benign disease, may be complicated by a laryn- 
 geal eruption of a more or less serious character. 
 
 Anions other infections, no1 to mention diphtheria which, of 
 of course, heads the list, we find erysipelas, which may presenl the 
 laryngeal complication in exceptional in tances: influenza, glaj 
 tuberculosis, syphilis, ;hkI leprosy. 
 
 Trachea and Bronchi. Tracheobronchitis i- of very frequenl 
 occurrence in the course of infections. It may he produced by 
 various microbes, the most specific as well as the mos1 common of 
 bacterial agents. Marfan lias endeavored to classify the various 
 types of bronchitis. 1 The following table, which we borrow from 
 this author, gives a good idea of the main varieties encountered and 
 of the mechanism governing their development: 
 
 Bronchitis of influenza. 
 Bronchitis of whooping-cough. 
 Bronchitis of measles. 
 Bronchitis of diphtheria. 
 Bronchitis of anthrax. 
 Specific . . Bronchitis of bubonic plague. 
 Bronchitis of tuberculosis. 
 Bronchitis of variola. 
 Bronchitis of malaria. 
 Bronchitis of glanders. 
 Bronchitis of svphilis. 
 
 Cold. 
 
 Previous specific bronchitis. 
 Chronic affection of the 
 lungs, pleura, and medi- 
 Originating astinum. 
 
 on the spot. Inhalation of irritating sub- 
 Bronchites mucous - stances. 
 
 membrane Intoxications, 
 altered by Chronic organic or diathetic 
 affections. 
 By autoin- Adynamic conditio: - 
 
 fection. phoid fever, acute diseases of 
 
 long duration, each' - 
 Spreading from the upper 
 respiratory tracts. 
 
 f Bronchites 
 i of gastroin- 
 Through the I testinal ori- 
 L tant parts I blood current . gin. 
 
 Bronchites 
 by septice- 
 [ mias. 
 
 Non-specific 
 (generally due 
 to pneumococc! 
 and strepto- 
 cocci). 
 
 Originating 
 I from dis- 
 
 Bv hetero- f 
 
 Contagion bv inhalation. 
 
 1 Marfan. Maladies des bronches 
 vol. vi.. p. 2S4 
 
 j_ infection (. 
 
 Traite" de ni£decine. 2d edition. Paris, 190], 
 
458 INFECTIOUS DISEASES. 
 
 The respiratory tract, at least in its upper parts, being inhabited 
 by innumerable microbes, the most ordinary causes which directly 
 or indirectly disturb the mucous lining may offer to common 
 bacteria an opportunity to exert their pathogenic action. It is 
 readily conceivable that even when bronchitis seems to be of a 
 specific nature, as is the case in measles, a secondary infection may 
 intervene to modif}^ its course. The fact that (rubeolic) bronchitis 
 is an early and constant accompaniment of measles proves that it 
 is due to the specific parasite of the infection; it rapidly resolves, 
 but, dming its short duration may permit common-place micro- 
 organisms to assume an aggressive attitude, and thus prolong the 
 bronchial inflammation, and, if sufficiently exalted, give rise to 
 bronchopneumonia. 
 
 The same is true as regards variola. Variolar pustules may be 
 produced in the bronchi and often become the starting point of a 
 pseudomembranous process. Apart from this specific bronchitis, 
 ordinary bronchitis is often observed in variola, and seems to be due 
 to the pneumococcus ; such bronchites were very frequent during 
 the Paris epidemic of 1900. We must also mention the bronchitis 
 of typhoid fever. It is an almost constant complication, appearing 
 on the fourth or fifth clay and lasting until the period of convalescence 
 It is generally attributed to common bacteria of the respiratory 
 tract. 
 
 In most cases bronchitis is not of grave character; when intense, 
 however, it may embarass hematosis and cause troublesome cough- 
 ing. In weakened individuals it tends to become purulent, and 
 gives rise to a secretion which obstructs the respiratory passages, 
 is with difficulty eliminated, and induces secondary lesions in the 
 pulmonary parenchyma, even bronchopneumonia. As a result of 
 this stagnation of the purulent secretion, gangrene in the smaller 
 bronchial tubes may occur, owing to invasion of saprophytes. This 
 however, is an incident of rare occurrence. 
 
 Lastly, we may mention pseudomembranous bronchitis which, 
 when very extensive, may cause death by asphyxia. This may 
 occur notably in diphtheria, as I have pointed out in a previous 
 chapter (p. 177). 
 
 The Lungs in Infectious Diseases. 
 
 Preliminary Considerations of Normal Physiology. Pulmonary 
 lesions are very frequent in the course of infectious diseases. Some 
 
INFLUENCE OF INFECTIONS UPON THE ORG INI8M. ir/i 
 
 disseminated rales are commonly heard during life; al the necri 
 parenchymatous alterations are almo I alwayt di closed,which are 
 spoken of as congestive phenomena. 
 
 The in I crest of pulmonary le ion appear to be more considerable, 
 as the lungs are charged with more importanl function- than was 
 once believed. It' this organ had aothing else to do than ensure 
 gaseous exchanges and hematosis, even then it would be considered 
 of vital importance. In addition, however, i1 play* a protective 
 role for the entire organism against infect inn- and intoxications. It- 
 action upon microbes has already been described (pp. 156-159). Its 
 act, ion upon poisons is hy no mean- less important, since microbes 
 act by virtue of the toxins they secrete. It had long been known 
 that the lung served as an eniunctory for volatile substances. The 
 offensive breath noticed in patients in the course of infections, 
 especially when these are accompanied hy excessive intestinal putre- 
 factions, suffices to demonstrate the elimination hy the respiratory 
 organs of certain principles — sulphuretted hydrogen, methylamer- 
 captan, ammonia, volatile bases, etc. Modern researches have 
 further demonstrated that the lungs also act upon those substances 
 which they do not eliminate by subjecting them to modifications 
 analogous to those accomplished by the liver. The importance of 
 this fact is evident, since all soluble substances, whatever their mode 
 of entrance may he, must pass through the pulmonary network 
 before reaching the nerve centres. 
 
 The action of the lungs upon poisons has received experimental 
 demonstration. The writer experimented with strychnine sulphate 1 
 and ammonium carbonate; Boeri and Giuranna, 2 and Cafiero 3 expe- 
 rimented with twelve poisons; in all these cases the protective action 
 of the lungs was more or less marked. 
 
 We may safely conclude that the lungs act as protective organs 
 against infections and intoxications. It may therefore he asked 
 whether the disturbances observed in the course of infections of the 
 respiratory apparatus are simply due to asphyxia or whether intox- 
 ication by pulmonary incompetency occurs as in the case of hepatic 
 incompetency. 
 
 1 Roger. Action des organes sur la strychnine. La Presse Medicale. April 15. I - - 
 Action des poumon, sur quelques substances toxiques. Ibid.. June 7. l x 
 
 2 G. Boeri and G. Giuranna. L'azione protettiva del pulmone. La Riforma niedica, 
 Dec. 2 and 3, 1S99. No. 07. 
 
 3 Cafiero. Recerche exp. sull' azioue protettiva del pulmone. Gazetta degli ospedali 
 ■e delle cliniche, 1S99, No. 97. 
 
460 ISFECTIOUS DISEASES. 
 
 Respiratory Disorders. The respiratory manifestations occurring 
 in The course of infections may consist simply of functional disturb- 
 ances of nervous origin or be dependent upon blood alterations. 
 Certain paroxysms of dyspnea observed in the beginning of scarlatina 
 may be connected with these nervous influences. At a more ad- 
 vanced period changes in the respiratory rhythm may characterize 
 certain grave nervous forms or indicate paralysis of the bulbar 
 centres, as in diphtheria, or express some cerebral or meningeal 
 complication. Dyspnea may also be due to blood alteration. Such 
 is notably the case in hemorrhagic variola. The panting respiration 
 is at times the only symptom expressing the gravity of infection. 
 In such cases, while the condition of the skin is serious, the general 
 state often seems to be very satisfactory, and the consciousness of 
 the patient is so perfect as to render it difficult for those around 
 him to believe that he will die within a few hours. 
 
 Modifications in the respiratory rhythm, dyspnea or Cheyne- 
 Stokes type of breathing, expressing a renal complication, are likewise 
 due to blood alteration. Such, however, is not always the case. 
 In the course of infectious nephritis dyspnea may often occur as a 
 result of acute pulmonary edema. 
 
 Classification of Pulmonary Lesions of Infectious Origin. The 
 lesions attacking the lungs may be divided into three groups, accord- 
 ing as the process is one of primary infection, secondary localization 
 of a specific process, or dependent upon ordinary bacteria. 
 
 The lungs may be the primary or exclusive seat of a well-deter- 
 mined infection. It is to be noted that while fibrinous pneumonia 
 manifests, by its clinical features and lesions, indisputable autonomy, 
 and seems to be worthy of classification among specific infections,, 
 it falls, in view of its microbe, to the rank of non-specific infections. 
 As a matter of fact, the pneumococcus is a quite commonplace agent, 
 capable of giving rise to very different processes, such as bronchitis 
 and bronchopneumonia, In fact, clinical study and anatomico- 
 pathological investigations have thrown down the barriers once 
 established between lobar and lobular pneumonia. These two pro- 
 cesses are connected one with the other by a number of transitions,, 
 so that pneumonia has somewhat lost its specific character. 
 
 The lungs may be attacked by a specific process invading them 
 primarily or secondarily in an exclusive, predominant, or accessory 
 manner. The fact that the respiratory apparatus freely communi- 
 cates with the exterior explains the easy arrival of morbid germs. 
 
ini<'i 1 (ii<:n< i i<: OF INFECTIONS UPO& THE ORGANISM. ]<;\ 
 
 It is hardly necessary to mention the frequency of pulmonary tuber- 
 culosis and the possibility of primary infection of the lunge by an- 
 thrax and glanders. 
 
 Anatomical and functional modifications occurring in the lung in 
 tho course of infectious diseases are more important. Two kinds of 
 lesions develop: some resull from the localization of the principal 
 agent) others depend upon an additional infection. Of late the 
 importance :unl lYc<|ii<'iicy of secondary infections iii the lunge have, 
 perhaps, been somewhal exaggerated. Every bronchopneumonia 
 occurring in the course of infections is generally considered as a 
 superadded process. The primary disease is 3upposed to play simply 
 a predisposing role. It is well to remember thai the situation is the 
 same as in the case of the throat. The greal number of microbes 
 present in the upper parts of the respiratory apparatus which, when 
 the mucous membrane is dried by fever, may be carried down to the 
 deeper parts by the air current, accounts for the frequency of inva- 
 sions by ordinary microbes. The latter, however, may do no more 
 than play a secondary role. An important point must be noted here. 
 These common microbes, being capable of developing more readily, 
 inhibit the development of others in artificial culture media; hence 
 the possibility of errors in interpretation. These considerations are 
 supported by the researches of Dr. Lesage, who believes that bron- 
 chopneumonia of measles depends upon the specific microbe of the 
 latter disease. The author has also noticed that in variola the pul- 
 monary foci at times contain very few bacteria, while, on the other 
 hand, large numbers of the special elements which seem to be char- 
 acteristic of this infection are present. 
 
 We are thus led to the question whether lobular pneumonias 
 alw r ays result from propagation of the process from the smaller 
 bronchi — i. e., an infection spreading from the bronchial ramifica- 
 tions toward the alveoli. Is it not likely that the lesion is often 
 produced by propagation of the process through the bloodvessels? 
 The pathogenic germs, on arriving through the blood cm-rent at the 
 capillaries of the lungs, are arrested there and give rise to an inflam- 
 matory process. In fact, when it is remembered that some conges- 
 tion or even splenization is discovered in almost every necropsy, the 
 endogenic origin of certain infectious processes seems highly probable. 
 
 Pulmonary lesions may be divided into six varieties: congestion, 
 splenization, lobular pneumonia, lobar pneumonia, hemorrhage, and 
 gangrene. 
 
462 INFECTIOUS DISEASES. 
 
 The expression pulmonary congestion is of too common use to be 
 discarded. It is not, however, an exact expression. Necropsy 
 always reveals more important alterations than the term in question 
 indicates. What is observed is not simply dilatation of the vessels; 
 there are exudates and serous effusions appreciable by the unassisted 
 eye. When the parenchyma is compressed, a frothy and aerated 
 fluid comes out. A certain degree of edema is, therefore, added to 
 congestion. Histological examination confirms this finding, and 
 chemical analysis further demonstrates the presence of an exudate 
 in the alveoli. It is to be remembered, therefore, that some albu- 
 minous effusion, more or less rich in cells, is always found. Some 
 of the cells originate from desquamation of the alveoli; others repre- 
 sent various leucocytes. 
 
 On examining the lungs of individuals dead of infections, it is 
 often noted that crepitation is not well marked at certain points, 
 particularly in the posterior and lower parts : the lung tissue presents 
 a red color, somewhat bluish or blackish. This condition is desig- 
 nated splenization, but the lesion is really more pronounced than 
 this term, adopted in view of the macroscopic appearance, indicates. 
 
 Coincident^ with the latter lesion, foci of pneumonia are observed. 
 This does not mean that splenization represents the first stage of 
 hepatization. The process is different, and splenization at many 
 points gives way to hepatization. The latter is characterized, as is 
 known, by a transformation of the tissue, which becomes dense, air- 
 less, red or gray in color, and, at least when it is red, resembles the 
 tissue of the liver. This hepatization takes place in two different 
 ways: Sometimes it affects the lobules individually; at other times 
 collectively. This distinction is expressed by the terms lobular and 
 lobar pneumonia. There is no essential difference between the two 
 processes. The lesions considered in themselves may be identical: 
 they ma}' - be equally rich in cells and contain the same amount of 
 fibrin. In true pneumonia, however, all the parts of a lobe are 
 attacked simultaneously, and all present the same stage of evolution, 
 so that on section we obtain a homogeneous slice. In lobular pneu- 
 monias, even when they are of pseudolobar type, the lobules are 
 invaded one by one, so that on section we see different appearances : 
 the process is more advanced in some than in other lobules. More- 
 over, since in most cases all the lobules of a lobe do not participate 
 in the same process, the result is a mixture of complex lesions, so 
 that by the side of foci of hepatization or of a nidus of broncho- 
 
INFLUENCE OF INFECTIONS UPON THE ORGANISM. 463 
 
 pneumonia, as it is sometimei called, we may ee le ion of another 
 order edema, splenization, or emphysema. 
 
 Lobular is far more frequenl than lobar pneumonia in the co 
 of infections. The latter may, however, occur in the beginnh 
 the most diverse diseases. The mosl common ai ociation i- that of 
 typhoid and pneumonia. These pneumonias, appearing from the 
 star! of an infection, occur in individuals capable of reacting in an 
 almost normal manner,and generally run a favorable course, behav- 
 ing like plain pneumonias. The author observed a case in which 
 pneumonia and scarlel fever appeared simultaneously, and the evo- 
 lution ran its course in a regular manner. Likewise, during con- 
 valescence pneumonias are ofien benign and presenl nothing special. 
 On the contrary, during the stationary period pneumonias po 
 special diaraders: the beginning frequently escapes observation ; the 
 crepitant rale is absent or does not present the classical features: 
 small moist rales only are heard. In other instances the blowing 
 murmur is observed from the first. The reactionary phenomena are 
 variable. At times dyspnea or aggravation of the general state of 
 the patient, as expressed by high temperature, dryness of tongue, and 
 acceleration of the pulse, load to auscultation of the lungs. Evolu- 
 tion is sometimes extremely rapid: those pneumonias are capable of 
 killing in a few hours. When life is prolonged the focus manifests 
 a tendency to spread and undergo purulent transformation, and 
 invade the pleura. If the patient survives, resolution of the lesion- 
 is tedious. In fatal cases necropsy reveals hepatization to be less 
 dry and less rich in fibrin than in cases of plain primary pneumonia. 
 
 Lobar and particularly lobular lesions are also liable to invasion 
 by saprophytes and to gangrenous transformation. It must be recog- 
 nized, however, that pulmonary gangrene has become very rare, if 
 we except those cases in which it is due to disorders of deglutition. 
 as is observed in diphtheritic paralyses. 
 
 The last pulmonary manifestation to be observed is hemorrl 
 This may occur in the form of a circumscribed infarct or a diffuse 
 infiltration. The latter variety is especially frequent in those infec- 
 tions which produce important blood alterations, notably in hemor- 
 rhagic variola. It may. however, be encountered under other cir- 
 cumstances. At the necropsy of an individual dead of a malignant 
 scarlatina the author found diffuse hemorrhage in both lungs. He 
 also observed intense congestion in the right and diffuse hemorrhage 
 in the left lung of a man who died on the fourth day of an erysipelas 
 
464 
 
 IXFECTIO US DISEASES. 
 
 with progressive asphyxia and high temperature. Circumscribed 
 hemorrhagic foci may also develop as an epiphenomenon in a nidus 
 of bronchopneumonia, or they may result from small emboli sent by 
 the heart or vessels, or, finally, by circumscribed thromboses. 
 
 Among these various manifestations lobar and lobular pneumonias 
 are undoubtedly the most frequent. Their frequency varies accord- 
 ing to the disease and the age. The author's statistics show, in this 
 connection, that measles stands at the head of the list; next come 
 erysipelas and diphtheria; variola occupied the fourth position. 
 Pulmonary complications are altogether exceptional in scarlatina and 
 varicella. 
 
 The influence of age may be seen if all the observations of the 
 author are put together regardless of disease. The patients are 
 divided into three groups with regard to age : (1) First childhood— 
 i. e., below two years of age; (2) second childhood — i. e., from two 
 to fifteen years of age; (3) above fifteen years of age. It is thus 
 found that pulmonary complications are thirty times less frequent 
 for the same diseases in adults than in children below two years of 
 age. This can be seen from the following table: 
 
 
 Cases with 
 
 
 
 
 Number of 
 
 Pulmonary 
 
 Fatal 
 
 Percentage. 
 
 Observations. 
 
 Lesions. 
 
 Cases. 
 
 Morbidity. 
 
 Mortality 
 
 First childhood . 613 
 
 134 
 
 70 
 
 21.9 
 
 11.4 
 
 Second childhood 974 
 
 67 
 
 17 
 
 6.9 
 
 1.7 
 
 Adults . . . 6445 
 
 48 
 
 33 
 
 0.7 
 
 0.5 
 
 Total 
 
 8032 
 
 249 
 
 120 
 
 3.1 
 
 1.4 
 
 The author's observations further show that pulmonary complica- 
 tions do not occur with the same frequency, as regards the age, in 
 the various diseases under consideration. Here is the result of our 
 
 statistics : 
 
 Classification of Infections in the Order of Decreasing Frequency of 
 Pulmonary Complications. 
 
 First Childhood. 
 
 
 Second Childhood. 
 
 Ad 
 
 ults. 
 
 Measles, 31.0 per 
 
 cent. 
 
 Diphtheria, 22.2 
 
 per cent. 
 
 Erysipelas, 
 
 6.2 per cent 
 
 Diphtheria, 2S.5 ' 
 
 
 Measles, 20.7 
 
 " 
 
 Variola, 
 
 2.3 " 
 
 Scarlatina, 10.7 ' 
 
 
 Variola, 3.2 
 
 " 
 
 Diphtheria, 
 
 0.9 
 
 Erysipelas, 9.0 ' 
 
 
 Scarlatina, 1.3 
 
 " 
 
 Measles, 
 
 0.6 
 
 Variola, 9.3 ' 
 
 
 Erysipelas, 0.0 
 
 " 
 
 Scarlatina, 
 
 0.2 
 
 Varicella, 1-0 ' 
 
 
 Varicella, 0.0 
 
 " 
 
 Varicella, 
 
 0.0 
 
 When the relative mortality in pneumonia is examined an unex- 
 pected fact is met with, namely, that bronchopneumonia of measles 
 
INFLUENCE OF INFECTIONS UPON THE ORGANISM. \r,r, 
 
 is the complication most often curable. Finally, if we consider 
 gravity according bo age, we see that, in the majority of infections, 
 recovery is niosi, frequent during second childhood. Adults are sel- 
 dom attacked, but when they are theprogno is is very unfavorable, 
 since the mortality varies from 50 to 75 per cent. The following 
 summary shows the facts in this respect: 
 
 i ■ , ■ rUagt of ' I 
 Pulmonary /<* 
 
 First childhood 
 
 Second child! I 
 
 A. lulls 
 
 Tims an adult attacked by bronchopneumonia ha- less chance of 
 recovery than a child under two years of ;igc. 
 
 Pleuritic Lesions in Infections. When there is a septic or non- 
 septic lesion in neighboring parts, and notably the lungs, the pleura 
 readily reacts; hence the frequency of pleurisies in the course of 
 various infections. Inflammation in this serous membrane may be 
 expressed by the production of fibrinous exudate, thickening, or 
 pseudomembranes. Dry pleurisies represent a defensive process 
 which often circumscribes the pulmonary lesion and in certain 
 instances prevents rupture of the lung. When inflammation is 
 intense, effusion takes place, which effusion may be serous, purulent, 
 putrid, or hemorrhagic, according to the state of the subject and the 
 nature of the pathogenic agent. 
 
 Serous Pleurisies. Serous pleurisy often develops in the absence of 
 any appreciable pulmonary manifestation. It has long been the 
 general belief, therefore, that it may be produced by such common 
 causes as cold. Since the contributions of Landouzy, Kelsch, Kiener, 
 Chauffard, and Gombault, and on clinical as well as anatomico- 
 pathological and experimental grounds, pleurisies from cold are 
 rejected, and the general opinion is that any pleurisy which cannot 
 be accounted for must be considered suspicious, as it is almost always 
 dependent upon tuberculosis. The author says almost always, as it 
 is conceivable that it may be caused by some other infection or by 
 a pulmonary alteration escaping observation. This restriction, how- 
 ever, does not lessen the importance of tuberculosis in the genesis 
 of apparently primary pleurisies. The importance of the pleurisy 
 may be so great as to relegate the pulmonary lesion which has caused 
 it to the background, and. as the pleuritic inflammation may resolve 
 and disappear, the physician naturally hesitates to admit the tuber- 
 cular nature of such a benign process. It is even probable that 
 
 30 
 
466 INFECTIOUS DISEASES. 
 
 serous pleurisy represents a favorable reaction and promotes recov- 
 ery. The best treatment of a diseased organ is, indeed, to impose 
 upon it perfect rest. By compressing the lung, by preventing its 
 expansion, by immobilizing it more or less completely, pleurisy 
 diminishes its activity, and thus realizes the major indication dis- 
 covered by therapeutists. There is, therefore, a growing tendency 
 to respect effusions. Barring those cases in which the effusion be- 
 comes dangerous by reason of its too great amount, puncture is to 
 be avoided. Thoracentesis is indicated at a later period when there 
 is reason to believe that the acute tubercular attack which caused it 
 is overcome. When the exudate of serous pleurisies is examined, 
 no microbe is generally detected. It may be assumed that the 
 microbes are localized in the diseased membrane or that pleurisy is 
 due to the action of toxins secreted in the pulmonary foci. In some 
 instances examination of the effusion reveals the presence of bacteria 
 and even pyogenics. As a rule, these are few in number, and the 
 fluid must be submitted to centrifugation in order to detect them. 
 Under these conditions, streptococci may be found which, being 
 probably attenuated by the germicidal power of the effusion, have 
 not been able to give rise to a suppurative process. 
 
 Pneumonia is admitted to be the most frequent cause of serous 
 pleurisy. The effusion is produced during the stationary period or 
 convalescence. Acute articular rheumatism is given the second 
 place ; then come eruptive fevers, typhoid, influenza, and whooping- 
 cough. Serous pleurisy has also been observed in septicemias, pye- 
 mias, and even in the course of gonorrhea. It may safely be assumed 
 that in all such cases the pleural effusion is caused by a pulmonary 
 lesion which is too small to be appreciated or is masked by the pleural 
 lesion. Serous pleurisy, however, is not of frequent occurrence in any 
 of the infections above mentioned, except typhoid fever. If reference 
 is made to the author's statistics, but four cases of serous pleurisy 
 are found. During convalescence from variola, measles, scarlatina, 
 and erysipelas patients developed fever and complained of pain in 
 the side. Auscultation revealed the presence of pleural effusion, the 
 serous nature of which was verified by an exploratory puncture. In 
 all four cases recovery was effected spontaneously within ten days. 
 Inoculations with these exudates was not practised; it is, therefore, 
 an open question whether the effusions depended upon latent tuber- 
 culosis, the acute infection having played simply the role of an inci- 
 dental cause. 
 
INFLUENCE OF INFECTIONS UPOH THE ORG I VI \[. \i,7 
 
 Purulent Pleurisies. After the details given iii treating of suppura- 
 tion (p. 222), the author will not dwell upon the hi tory of purulent 
 pleurisies. They develop under the same condition a pleu- 
 
 risies, and are connected with these by a erie of transitioi 
 two processes are nol distinct. Although in mosi cases pleuri 
 purulent from the beginning, it is uol rare to Bee a primarily serous 
 effusion become purulent. Slight modification* in the virulence of 
 pathogenic agents suffice to accounl for the difference* in the pr< 
 
 Purulent pleurisy may occur in the course of various pneumoniae 
 and aggravate prognosis. A certain amounl of pus is often found in 
 the pleura, whether the case be one of ordinary pneumonia or i 
 ondary one complicating measles, variola, or erysipelas. 
 
 Purulent pleurisy as an affection apparently independent of a 
 pulmonary lesion is not of frequent occurrence. The author has 
 observed several such cases. One occurred in a woman profoundly 
 infected by gonorrhea; she developed a seropurulenl pleurisy which 
 was spontaneously cured in a month. 
 
 Hemorrhagic Pleurisies. As gangrenous and putrid pleurisies have 
 already been referred to (p. 240) the author's intention is here to 
 say a few words with reference to hemorrhagic pleurisies. This 
 variety of effusion when not dependent upon cancel- is generally due 
 to rapid tuberculosis. It is at times observed in pneumonia and 
 bronchopneumonias; it may occur in the most varied infection! 
 a result of infectious infarcts (Ehrlich), but in the majority of in- 
 stances it is a complication of typhoid fever. The author does not 
 refer to bloody effusions observed in hemorrhagic infections: these 
 are cases of hemothorax, not of pleurisies. 
 
 In typhoid fever the effusion may be sero-hemorrhagic. A similar 
 effusion may occur in pleurisies of convalescence. There are also 
 pleurisies with Eberth's bacillus which appear independently of 
 typhoid fever. The author has reported such a case studied in con- 
 junction with Dr. Charrin. 1 A similar case was published by Kelsch. 
 Tracheobronchial Adenopathies. The various lesions of the respir- 
 atory apparatus readily influence the tracheobronchial ganglia. 
 At the necropsy of individuals dead of pulmonary affections, espe- 
 cially in the case of children, these glands are found enlarged, red. and 
 inflamed. These acute glandular inflammations commonly subside 
 with gratifying rapidity. They persist, however, in certain install - 
 
 1 Charrin and Roger. Presence du bacille d'Eberth dans un epanckement pleural 
 hemorrhagique. Soc. medieale des hdpitaux, April 17. 1891. 
 
468 INFECTIOUS DISEASES. 
 
 and explain the cough resembling that of whooping-cough occurring 
 consecutively to measles, typhoid fever, and particularly influenza. 
 
 In the absence of pulmonary lesions, some infections may cause 
 hypertrophy of the tracheobronchial glands. Whooping-cough is 
 quite notable in this connection. It has also been asserted that, 
 owing to lymphatic anastomoses, anginas and erysipelas of the face 
 may produce enlargement of these glands. 
 
 Since the works of Loomis and Pizzini a new problem confronts 
 us. Koch's bacillus is often found in apparently healthy tracheo- 
 bronchial glands in individuals presenting no trace of tuberculosis. 
 Kalbe has verified this fact and estimates at 8 per cent, the propor- 
 tion of glands which, though seemingly sound, contain the bacillus. 
 The tubercle germ thus remains inoffensive until an intercurrent 
 disease diminishes the resistance of the organism. The infections 
 which easily affect the bronchial glands are those most capable of 
 thus giving rise to an attack of tuberculosis. It is therefore readily 
 conceivable that whooping-cough and measles play a notable role 
 in this connection. 
 
 Remote Consequences of Infectious Lesions of the Respiratory 
 Apparatus. As is the case in lesions of other parts of the organism, 
 so those of the respiratory apparatus may be completely cured. 
 When, however, the3^ are profound or repeated, these lesions are 
 often followed by irremediable alterations. Emphysema of an almost 
 incurable character and even splenization are often observed after a 
 bronchopneumonia. The author is therefore inclined to refer to 
 lesions of early age the pulmonary emphysema so frequently 
 observed in adult and advanced age. 
 
 As in other parts, cicatrization of lesions may give rise to sclerosis. 
 When the lung is involved in the process the alveolar walls and 
 vascular ramifications are thickened. The same lesion is observed 
 in the pleura, which becomes thickened at certain points, or its two 
 layers may be adherent to each other. Finally, sclerotic lesions may 
 increase emphysema and at times cause bronchial dilatations. 
 
 It is thus possible to connect various chronic lesions which fre- 
 quently coexist and seem to be the remote results of changes arising 
 from infections. 
 
CHA I'TKIi X V I. 
 
 INFLUENCE OF INFECTIONS UPON THE VARIOUS PARTS 
 OF Till; ORGANISM (Concluded , 
 
 Buccopharyngeal Manifestation in Mea lea. Buccopharyngeal Manifestation 
 Scarlatina. Buccopharyngeal Manife tation of Varicella and Variola. Bui 
 pharyngeal Manifestations in Various Infections. Stomach Disturbance* and 
 Lesions of the Intestine in Infection Amebic Dysentery and Bacteria 
 Cholt'riform and I lyscntrriform lOiitcriles. Cholerifonn Gastroenterite and - 
 sonal Diarrheas. Dysenicrilorm Knterite [nfluence of [nfectious Di ea • upon 
 the Liver. General Characters of the Infected Liver. Semiology of the [nf» 
 Liver. Action "f Infections upon the Pancreas. Influence of Infections upon the 
 Kidneys. Influence of Infections upon the Genital < 'rgans. Influence of In feet ions 
 upon Menstrual ion. Influence of Infections upon Pregnancy. Suckling by [nf< 
 Women. 
 
 Influence of Infections upon the Digestive Apparatus. 
 
 In examining a patient the physician generally does not overlook 
 
 the condition of the tongue. This inquiry is particularly important 
 in infectious diseases, as it may give diagnostic and prognostic indi- 
 cations of considerable value. A tongue which is excoriated on the 
 borders is a good sign of typhoid fever; an opaline or porcelain 
 tongue is quite peculiar to influenza; the red, raspberry-like tongue 
 is observed especially in scarlatina. From a prognostic standpoint 
 the importance of moisture or dryness of the tongue is well known. 
 When this organ manifests a slight trembling extending to the lips 
 and rendering speech jerky it indicates the imminence of delirium 
 tremens. 
 
 Lesions of the mouth and throat are extremely frequent in the 
 course of infectious diseases; but their study is difficult, and the 
 differential characters ascribed to them are not very certain. Even 
 bacteriological examination is not free from considerable difficulties 
 and not infrequently leads to errors. In fact, the buccal cavity is 
 widely open, and even under normal conditions is inhabited by 
 multitudes of microbes. Microscopic examination and cultivation 
 always reveal bacterial associations (p. 145\ 
 
 It has. however, been possible to determine certain clinical types 
 corresponding to a bacteriological formula. In the first place, diph- 
 
470 INFECTIOUS DISEASES. 
 
 theria is such a type; then buccopharyngeal localizations of general 
 infectious diseases: the eruptive fevers, syphilis, and tuberculosis 
 give rise to well-determined buccal lesions. In some instances differ- 
 entiation is based upon clinical observation, and, therefore, it is pos- 
 sible to doubt its value. Such, for instance, is the case in scarlatinal 
 angina, which is considered by some authorities as an enanthema 
 produced by the scarlatinal virus, by others as a common inflam- 
 mation due to the streptococcus. This constant intervention of the 
 streptococcus in all buccopharyngeal inflammations further compli- 
 cates the question. Hence, as was indicated by Dr. Lemoine, when 
 the role of this agent is to be determined, it is necessary to look for 
 it in the deeper parts of the tissues ; for example, by puncturing the 
 tonsils, since if one is contented with buccopharyngeal exudates, 
 one may obtain a virulent streptococcus without having any right 
 to draw a conclusion from this experiment. In fact, it has been 
 demonstrated that certain germs are exalted in the course of various 
 diseases, which is particularly true as regards the microbes of the 
 mouth, and notably the streptococcus. We are thus able to explain 
 certain facts which would otherwise appear very strange. For 
 example, the saliva of a scarlatinal patient expelled into the phys- 
 ician's face is known to have produced erysipelas. The author has 
 observed a great number of simple sore throats contracted by indi- 
 viduals nursing scarlatina cases. Finally, what seems to be more 
 demonstrative is the fact that parents whose children suffered from 
 diphtheria contracted at their bedsides erythematous or exudative 
 anginas in which LoefTler's bacillus could not be detected. This fact 
 suffices to show that the diphtheritic microbe may favor exaltation 
 of the ordinary bacteria which, in their turn, produce by contagion 
 sore throats among those surrounding the patient. 
 
 Buccopharyngeal Manifestations in Measles. In measles an enan- 
 thema analogous to the cutaneous eruption is observed in the palate. 
 Like the latter, it appears in the form of small discrete spots of an 
 intense red color. Certain symptoms observable in the mouth enable 
 the physician to make an early diagnosis. Such is erythematous- 
 pultaceous gingivitis, to which Comby has drawn special attention : 
 a white coating, which is formed of desquamated epithelial cells, and 
 may readily be wiped out by slight friction, is seen upon the gums. 
 This manifestation is perfectly plain; it remains to be seen whether 
 it is specific. More value is attached to Koplik's sign, which is 
 appreciable as early as the first or second day of invasion, and disap- 
 
IN FLU UNCI', OF INFECTIONS UPON THE ORGANISM. 171 
 
 pears when the cutaneous eruption appears. The sign <■• 
 small, bluish-white, slightly elevated Bpo1 . urrounded by s red 
 circle, and varying in size from I mm. to 5 nun. (0.04 to o.'2 incl 
 and in number from five to twenty. These appear upon the mu< 
 membrane of the lips, tongue, and inner surface of the cheeke betv 
 the labial commissure and the opening of Stenon' <\u<-\. These pro- 
 ductions are formed of fatty epithelial cell , re i I friction, bu1 can 
 be removed by means of forceps. 
 
 These various manifestations should qo1 be mistaken \'<>v inflam- 
 matory processes; they are simple enanthemata. 
 
 Among buccal manifestations we musl note angina, which mi 
 observed during the invasion of measles. It is a complication of 
 exceptional occurrences, at least in adults. It may also be oba 
 during convalescence. The author has observed twenty-six such 
 cases. It is generally an erythematous, seldom a pultaceous, angina. 
 
 Buccopharyngeal Manifestations in Scarlatina. As is known, buc- 
 copharyngeal manifestations arc far more frequenl in scarlatina than 
 inmeasles. The angina is the initial phenomenon, and is never absent. 
 There are two principal hypotheses as to its nature: the buccophar- 
 yngeal symptoms may be considered as a simple enanthema, or it 
 may be held to be a true angina due to the microbe of scarlatina. 
 To the former opinion it may be objected that the inflammatory 
 phenomena are too intense and that, while a patient suffering from 
 measles does not say anything regarding his throat, a scarlatinal 
 patient first complains of pain in deglutition. This objection can 
 readily be answered by the statement that scarlatinal enanthema is 
 more intense; the difference is one of degree, not of nature. It pro- 
 duces alteration in the epithelium, and thus permits buccal germs to 
 cause further injury in the mucous membrane. It is also to be noted 
 that in certain cases of scarlatina angina is mild and the patient 
 suffers little; there are a great many intermediate degrees between 
 the mildest and the severest manifestations. 
 
 The other parts of the mouth are little affected, except the tongue, 
 which is involved in the eruptive process. From the third to the 
 sixth day the epithelium of the tongue is desquamated, and the organ 
 assumes a characteristic appearance comparable to that of a straw- 
 berry. It is not a glossitis, since the patient does not experience any 
 pain or any functional trouble. It is simply a process of desquama- 
 tion similar to that of the skin, and its early occurrence in the tongue 
 is explained by the moisture of the region. 
 
472 IXFECTIO US DISEASES. 
 
 The greater intensity of the scarlatinal exanthema explains the 
 frequency of secondary buccopharyngeal infections. The buccal 
 streptococcus is exalted and produces various alterations which 
 appear simultaneously with the specific angina, or a few days later, 
 and at times only during convalescence. 
 
 In scarlatina, as in measles, angina may assume a gangrenous char- 
 acter. This evolution occurred in two of the author's cases — chil- 
 dren; one of them thirteen months and the other three months old, 
 and both succumbed. The uvula and tonsils were completely sphace- 
 lated in both instances. Cultivation from the lesions revealed the 
 presence of streptococcus, staphylococcus, and a non-virulent anae- 
 robic microbe. 
 
 Buccopharyngeal Manifestations of Varicella and Variola. Vari- 
 cella and variola may also give rise to buccopharyngeal phenomena. 
 Here, however, the question is not one of erythema; vesicles and 
 pustules appear just as in the skin. The eruption is generally scanty 
 in varicella, and is produced in all parts of the mouth without dis- 
 tinction — cheeks, palate, tongue, and gums. Variolar eruption is of 
 greater importance. It sometimes appears early, and may then serve 
 as a diagnostic guide. When it appears at the same time as the 
 cutaneous eruption it evolves more rapidly, and thus, in doubtful 
 cases, when the diagnosis between measles and variola is undecided, 
 examination of the throat removes all doubt: papules and vesico- 
 pustules are seen occupying the palate, uvula, pillars, gum, tongue, 
 and cheeks. This eruption is very copious in coherent and confluent 
 variolas and causes dysphagia from the sixth or seventh day ; it may 
 then aggravate prognosis considerably by disturbing alimentation. 1 
 
 Buccopharyngeal Manifestations in Various Infections. We 
 might review all infectious diseases, since all may affect the buccal 
 cavity. Angina is frequently observed in typhoid fever, in which 
 its appearance is quite variable, being sometimes pultaceous, at times 
 ulcerative, and in other instances gangrenous. It is 'generally ad- 
 mitted that erysipelas frequently begins with throat symptoms. 
 This classical opinion seems to the author inexact. It must be due 
 to the fact that patients generally speak of sore throat when they 
 suffer from painful enlargement of the lymphatic glands often accom- 
 panying the cutaneous lesions, and sometimes preceding them by a 
 day or two. In two instances they existed four days before the 
 
 1 Coste. Quelques considerations sur le diagnostic, le pronostic et le traitement de 
 la variole. Marseille m£d., January, 1898. 
 
INFLUENCE OF INFECTIONS UPON THE ORGANISM. M .', 
 
 appearance of erysipelas. In om< ca e , bowe 1 1 
 angina does occur. In twenty of the author' il announced 
 
 fche onset of the disease. In a youth of fifteen year ol age erysipe- 
 latous inflammation started from the tongue, which was highly 
 swollen and very painful and presented a couple of bullae which 
 opened and gave issue to a sanguinolenl discharge. 
 
 Stomach. 
 
 Numerous observations have proved the involvemenl of the stom- 
 ach in infectious processes. The gastric disturbances may theoreti- 
 cally be classed in lour groups according as they are of nervi 
 muscular, chemical, or microbic origin. Unfortunately, accurate 
 investigations are lacking and are very difficult. Gastric chemism 
 can hardly be studied in the course of acute infections. In view, 
 however, of the coated condition of the mouth, the disgust i 
 rienced by patients for food, and frequent vomiting of undigi 
 aliments it may safely be assumed that the digestive secretions no 
 longer possess their normal characters. At any rate, i1 is in n< 
 to be wondered at that gastric secretion is also disturbed when all 
 the other secretions are. Moreover, chronic gastritis so often follows 
 the evolution of acute diseases that it seems perfectly rational to 
 assume a causal relation between the two processes. 
 
 As in many other visceral disturbances, vomiting is often of nervous 
 origin. We refer particularly to vomiting at the onset of infections. 
 It occurs soon after the initial chill, and accompanies the first symp- 
 toms. At this stage of evolution gastric alterations cannot be sup- 
 posed to have taken place, and, in fact, the vomiting is a transitory 
 incident. It is often observed in the beginning of scarlatina, measles, 
 and erysipelas. In the latter disease it sometimes represents the 
 first symptom of a relapse. Special mention must be made of the 
 initial vomiting in variola, occurring for twenty-four or forty- 
 eight hours coincidently with extremely intense pain in the epigas- 
 trium; its diagnostic value is no less important than that of rachi- 
 algia. 
 
 Vomiting during the stationary period and convalescence exj : - 
 on the contrary, gastric alteration. Hence they are more persistent 
 and have an unfavorable prognostic significance. It is to be acknowl- 
 edged, however, that they are not very frequently observed, and it 
 is surprising to see patients overcome their dislike for nourishment 
 and digest their food so well. It has thus been possible to feed 
 
474 / v/ I: < ' TJ OUS DISEASES. 
 
 typhoid cases. In the author's wards variolar patients receive rela- 
 tively abundant nourishment without any inconvenience. 
 
 Observations by Kalmus, Hayem, Lion, and others demonstrate 
 the possibility of an invasion of the gastric glands by microbes. Gas- 
 tric ulcerations of typhoid fever have long been known. Dieulafoy's 
 observations proved the gastric localization of the pneumococcus. 
 The same observer has called attention to heinatemesis occurring 
 in the course or at the end of an appendicitis or internal strangu- 
 lation. Having in several instances opened the stomach of indi- 
 viduals dead of variola, the author has sometimes found erosions 
 which are at times quite profound. Diffuse bloody infiltration with 
 numerous ulcerations may be found in cases of hemorrhagic variola, 
 explaining the occurrence of hematemesis during life. 
 
 These facts, which enable us to understand the mechanism of 
 acute gastric phenomena in the course of infections, may be cited in 
 support of the opinion that chronic ulcerations, notably simple ulcers, 
 are of microbic origin. The process is less intense and more slow 
 than in the case of acute disorders, and the lesion insidiously formed 
 gives rise to symptoms long after the termination of the infectious 
 malady of which it is a remote consequence. 
 
 Primary or predominant attacks by general specific infections are 
 rarer in the stomach than in other organs. Anthrax, tuberculosis, 
 and syphilis of the stomach are but exceptionally observed. In rare 
 cases phlegmonous gastritis may occur as a primary or a secondary 
 manifestation in pyemia, and, according to observations of Ziegler, 
 Mintz, and Derbek, seems to be due to the streptococcus. 
 
 Disturbances and Lesions of the Intestine in Infections. 
 
 Almost all infectious diseases produce intestinal disturbances. The 
 latter, like those of the stomach, may be of nervous, muscular, 
 chemical, or bacterial origin. The influence of bacterial action is 
 considerable ; numerous researches have demonstrated that intestinal 
 microbes, notably the colon bacillus, become virulent in the course 
 of infections. This fact has a double interest. When a highly viru- 
 lent bacillus is found in the intestine the disturbances observed may 
 be erroneously attributed to its action. On the other hand, the 
 increased activity of the intestinal germs accounts for certain local 
 symptoms, such as tympanites— perhaps favored by temporary 
 atony of the muscular fibers— diarrhea, and even certain general 
 manifestations, some kind of secondary digestive autointoxication. 
 
INFLUENCE OF INFECTIONS UPON THE ORG I VI H 176 
 
 This constant participation of the inte tine in infectiom proa 
 explains the developmenl of chronic condition : some individuals 
 continue to suffer from certain intestinal disorders, notably from a 
 tendency to diarrhea, on the slightesl dietetic error or cold; others 
 suffer from rebellious con tipation. The author has observed several 
 instances of mucomembranous enteritis. 
 
 \V' ( . are thus led to the question whether or no1 infections play a 
 r61e in the developmenl of appendicitis. This thi aus- 
 
 ible. The frequency of follicular lesions of the intestine give i1 
 support, but facts hardly respond to whal is expected. Only once 
 in our wards has the author seen appendicitis follow measles. On the 
 other hand, having examined a certain number of appendices al the 
 necropsy of individuals dead of various infections, particularly vari- 
 ola, the author has detected no lesions. The importance of ' 
 negative results should not be exaggerated, however. More numer- 
 ous investigations are required in order to determine the valu 
 the theory which is perfectly consonant with the data of general 
 pathology. 
 
 As already stated, intestinal functions seldom remain regular in 
 the course of infectious diseases. Sometimes constipation predom- 
 inates, as is the case in erysipelas; at other times, diarrhea which, by 
 reason of its too great severity, may prove fatal. Some authors have 
 described an intestinal form of scarlatina characterized by profuse 
 and incessant evacuations. As a rule, intense and generally bilious 
 diarrhea is observed in the beginning of measles; it seems to In- 
 dependent upon an intestinal enanthema. At a more advanced 
 period choleriform or dysenteriform diarrheas may appear which, 
 next to bronchopneumonia, represent the gravest complications of 
 the disease. This complication is particularly dangerous in the case 
 of children. The author has, nevertheless, observed the case of an 
 adult who, at the end of measles, succumbed to putrid pleurisy of 
 intestinal origin. 
 
 Even in a benign disease, such as varicella, intestinal disorders 
 may prove fatal in young children. It is, however, in variola that 
 this complication is of particular importance. Trousseau laid stress 
 upon the diarrhea of the invasion period, which ceases as soon as 
 the eruption appears. While constipation is the rule in slight cases 
 during the stationary period, diarrhea renders the prognosis unfav- 
 orable in serious cases. It is a fetid and profuse diarrhea, resisting 
 most medicaments, and is hardly checked by astringents and notably 
 
476 INFECTIO US DISEASES. 
 
 by preparations containing tannin. In hemorrhagic variola bloody 
 stools are frequent. In certain cases, especially toward the end of 
 the stationary period, the stools may contain a certain amount of 
 blood: this is a complication of importance, but does not render prog- 
 nosis particularly bad. In fact, the author's observations show that 
 of all visceral hemorrhages enterorrhagia, when alone, is the least 
 grave. 
 
 It is not necessary to describe the intestinal localizations of specific 
 diseases. As in the case of the stomach, localization of anthrax, 
 tuberculosis, syphilis, and actinomycosis may also occur in the intes- 
 tine. Tuberculosis of the stomach is an event of very rare occur- 
 rence, while it is quite frequent in the intestine, where it may assume 
 the most varied forms. 
 
 Amebic Dysentery and Bacterial Dysentery. In the classification 
 of infectious diseases (pp. 24-30) it was stated that two principal in- 
 fections localize themselves in the alimentary canal, viz., cholera and 
 dysentery. Typhoid fever, when classed with septicemias, might 
 also be included in this group; leaving it aside, however, the author 
 will consider only cholera and dysentery. The specific nature of the 
 former disease has been demonstrated by clinical observation and 
 epidemiology, as well as by Koch's discovery. The author must 
 expand at some length upon dysentery. Most clinicians hold it to 
 be a disease perfectly defined and possessing full autonomy. Bacte- 
 riological investigations, however, seem to lead to a quite different 
 conclusion. 
 
 Certain authorities attribute dysentery to amebae. Numerous 
 observations reported by Kartulis seem to be convincing. Recent 
 researches of Marchoux demonstrate that amebse may produce in 
 cats a disease analogous to dysentery and even induce hepatic 
 abscesses. This experimental result confirms those observations in 
 which protozoa only, in the absence of all bacteria, were found in 
 the pus of dysenteric abscesses of the liver. 
 
 Numerous observations have been recorded in which ameba3 
 were not found. On the other hand, bacteriologists have described 
 various bacteria detected in cases of dysentery. Some have noted 
 special microbes of the bacillary form (Ziegler, Babes, Ogata), or 
 presenting the appearance of diplococci (Silvestre) ; others have met 
 with bacteria which were already known, such as the streptococcus, 
 bacillus pyocyaneus, and proteus vulgaris. The majority of authori- 
 ties, however, have isolated bacilli related to the colon bacillus or 
 
INFLUENCE OF INFECTIONS UPON THE ORG A \is.m .177 
 
 •occupying an intermediate position between the latter and the 
 typhoid bacillus; it will suffice to cite the namee of Kiel,-. Chante- 
 incssc, Wiihil, ( i rigorierT, Laveran, Arnaud, and especially Oelli and 
 Shiga, who have recorded highly intere ting re earchee on thi 
 ject. 
 
 Kxperiment.ing with dysenteric dejecta kindly senl him by con- 
 freres practising in countries where the disease i endemic, the 
 author found no amebffl in any instance, bu1 a bacillus resembling 
 the ordinary bacillus coli. It readily developed in bouillon, to which 
 it imparted a very disagreeable put rid odor. Agar-agar was covered 
 by a viscid, thick layer; gelatin was aot liquefied, bul small gaseous 
 bullae weiv at limes seen iii its deeper j > ; 1 1 • i ~ : mill, was generally 
 coagulated within forty-eigh.1 hours, and the medium became acid. 
 On potatoes a yellowish culture was obtained. 
 
 What right have we to conclude thai this bacillus is the cause of 
 the disease? Have we not in the presence of the ordinary colon 
 bacillus, a constant resident of the human intestine? The question 
 is certainly difficult of solution. In favor of the pathogenic role of 
 this bacterium its action upon animals may be advanced, which 
 action varies according to the degree of gravity of symptoms observed 
 in man. Another argument in support of the pathogenic role of this 
 microbe is based upon the fact that it produces extremely powerful 
 toxins in culture media, The sterilized cultures when injected into 
 the veins of rabbits cause diarrhea which at times is so severe as 
 to be almost a continuous flow. These facts suffice to establish the 
 individuality of the dysenteric colon bacillus. Another fact which 
 imparts to it a particular feature and conclusively shows its patho- 
 genic role in man is that the serum of patients convalescent from 
 dysentery agglutinates the dysenteric colon bacillus, but does not 
 agglutinate the ordinary colon bacillus. This was noticed by the 
 author and by Celli and Shiga. Flexner 1 has obtained agglutination 
 with the serum of patients suffering from bacterial dysentery, while 
 the result has been negative in the case of amebic dysentery. The 
 history of dysentery is, therefore, to be divided into two. 
 
 Choleriform and Dysenteriform Ententes. Alongside of the spe- 
 cific intestinal infections spoken of above are to be placed common 
 infections which simulate them. 
 
 Choleriform gastroenteritis, which has long been known, resembles 
 
 1 Flexner. On the Etiology of Tropical Dysentery. Bulletin of the Johns Hopkins 
 Hospital, October. 1900. 
 
478 
 
 IXFECTIO US DISK. I sj-s. 
 
 genuine cholera by its symptoms. Distinction between the two has 
 been based upon epidemiological data. Bacteriology has demon- 
 strated the absence of the comma bacillus in such cases, of which 
 numerous examples are every year observed during the hot season, 
 even in temperate climates. Likewise, dysenteriform ententes are 
 met with in the form of small epidemics. The stools contain no 
 amebse, but a bacillus distinctly different from the dysenteric colon 
 bacillus above described. 
 
 The fact that such analogous manifestations are produced by 
 different parasites is not to be wondered at. It is well known that 
 certain poisonings are expressed by symptoms similar to those of 
 cholera; such, for instance, is the case in poisoning by tartar emetic. 
 On the other hand, intoxication by corrosive sublimate gives rise 
 to lesions and symptoms comparable to those of dysentery. Clinical 
 observation is not yet sufficient to give us an accurate idea of the 
 nature of all these acute ententes; it does not yet enable us to 
 trace them with certainty to their cause, to determine the infectious 
 agents responsible for their development, or even to discern with 
 precision infections from toxic manifestations. These remarks are 
 equally applicable to cholera and dysentery. Hence it seems to 
 me that the present task of the clinician is to determine and describe 
 the differential characters which will lead to definite distinction of 
 the diverse forms of dysentery and to concordance of clinical obser- 
 vations with bacteriological findings. 
 
 Choleriform Gastroenteritis and Seasonal Diarrheas. Seasonal 
 diarrheas may assume either choleriform or dysenteriform characters. 
 
 The frequency of choleriform diarrhea varies somewhat from one 
 year to another, as may be seen from the following figures : 
 
 
 >. 
 
 s> 
 
 
 
 
 
 
 
 £3 
 
 
 b 
 
 g 
 
 
 
 
 e 
 
 -« 
 
 
 
 
 
 CO 
 
 
 
 ? 
 
 
 Year. 
 
 s 
 
 e 
 
 
 
 a. 
 
 e 
 
 <0 
 
 I-* 
 
 1 
 
 1 
 
 "S, 
 
 O 
 
 © 
 
 to 
 
 u 
 
 c 
 o 
 Eh 
 
 1896 
 
 
 
 2 
 
 
 2 
 
 3 
 
 4 
 
 6 
 
 1 
 
 
 
 
 18 
 
 1897 
 
 
 
 
 
 1 
 
 4 
 
 10 
 
 5 
 
 
 
 
 
 20 
 
 1898 
 
 
 
 
 
 
 o 
 
 2 
 
 20 
 
 24 
 
 1 
 
 l 
 
 1 
 
 52 
 
 1899 
 
 
 4 
 
 . . 
 
 2 
 
 1 
 
 
 2 
 
 1 
 
 9 
 6 
 
 19 
 10 
 
 7 
 5 
 
 3 
 
 
 l 
 
 43 
 
 1900 
 
 27 
 
 Total 
 
 
 4 
 
 2 
 
 3 
 
 3 
 
 13 
 
 31 
 
 60 
 
 37 
 
 4 
 
 l 
 
 2 
 
 160 
 
 
 
 Seasonal influence, although undoubted, is not always the same.. 
 Some cases are at times met with during the cold season. The 
 greatest number, however, occur in August. This is indicated by 
 
INFLUENCE OF INFECTIONS UPON THE ORGANISM. 479 
 
 my statistics, but Full)' shown by those of the French army, h may 
 be seen therein, for example, tfyal the monthly morbidity of diarrhea 
 amounts to 750 cases in June, L350 in July, reaches L700 in Au| 
 and falls to looo or I LOO during the following month. 
 
 The influence of heat, ingestion of fruits and ice water do Dot 
 suffice id explain ihe genesis of the phenomena. 'I li'- rdle of water 
 must first be taken into account. The qoxou influence of the 
 latter was recognized byancienl observers, particularly by Hippoc- 
 rates, and has been demonstrated by numerous contributions of 
 recent period. It has thus been learned thai epidemics of diarrhea 
 sometimes coincide wifli (hose of catarrhal icterus, typhoid, and 
 malarial fevers. In Paris diarrhea and typhoid regularly appear 
 when, in summer, Seine water is drunk instead of spring water. It 
 should not be concluded, however, that alterations in water suffice 
 of themselves to account for the frequency of seasonal diarrhea. 
 Heat seems to disturb the functions of the intestine and hinder the 
 secretion of ferments; it leads to drinking of considerable quantities 
 of liquids which dilute and weaken the digestive juices. Moreover, 
 aliments are more readily altered and fermented in the hot season. 
 Lastly, a part is played by overexertion, as is so frequent ly observed 
 among soldiers during fall maneuvers and in the time of war. 
 
 Unlike genuine cholera, diarrheas, even when assuming choleri- 
 form appearance, do not seem to be due to a specific agent. The 
 opinion is gaining ground that the colon bacillus is the principal 
 agent concerned. This microbe acts by secreting toxic substances 
 in the alimentary canal, and thus gives rise to the development of 
 morbid manifestations. The principal poison contained in the stools 
 was found by Dr. Robert, who pursued researches in our laboratory, 
 to be a substance which is precipitated by alcohol. Its injection 
 into the rabbit causes diarrhea, hypothermia, myosis, and at times 
 nystagmus and convulsions. If the animal recovers, hypothermia 
 is followed by hyperthermia, which may be considered as a reaction 
 of the organism. These results, when compared with those obtained 
 by the employment of sterilized cultures of the colon bacillus, lead 
 us to the conviction that the symptoms of gastroenteritis may 
 readily be explained by the theory of intoxication. Some author- 
 ities hold dehydration responsible for cramps. This interpretation 
 is not plausible, since the intensity of cramps is related to the 
 gravity of the phenomena rather than to the amount of a 1 vine 
 evacuations. Moreover, cramps may appear with the first stools. 
 
480 INFECTIO US DISEASES. 
 
 and may at times precede them. 'When the general condition is 
 improved, cramps disappear, while diarrhea still continues. 
 
 The toxins are rejected by means of vomiting and diarrhea, which 
 represent reactionary phenomena designed for the elimination of 
 the poisons. Hence, administration of a purgative and lavage of 
 the stomach often relieve the disturbances by completing nature's 
 task. 
 
 Among the organs affected the liver must first be mentioned. 
 In one-eighth of the cases this gland is enlarged and often painful 
 on palpation. The liver must struggle against the toxins and 
 protect the organism; but it is often injured in its resistance, for 
 this organ is constantly found degenerated at the necropsj'. The 
 kidneys are seldom involved, albuminuria is quite rare, which I 
 have observed only in one-seventh of the cases. 
 
 The mortality from seasonal gastroenteritis is not very high. 
 Out of a total of 160 patients we lost 14 (8.7 per cent.). In most 
 cases death occurs at the end of three or four days. In certain 
 instances, however, it supervenes speedily. Thus, a young man, 
 twenty-three years of age, was taken sick on August 26, 1899, at 
 6 a.m., with fetid diarrhea and vomiting. He was brought to the 
 hospital on the same clay at 4 p.m. The face was cyanosed, the 
 extremities cold and blue, the pulse thready, the patient unconscious 
 with a central temperature at 105.1° F. (40.6° C). In spite of 
 injections of caffein and of artificial serum he succumbed an hour 
 later, less than twelve hours after the onset of the attack. At the 
 necropsy intense congestion of the intestines, prominence of Peyer's 
 patches, and dilatation of the right heart were the only alterations 
 discovered. 
 
 Dysenteriform Enteritis. Dysenteriform enteritis is observed, 
 especially in children, and is not as frequent as choleriform enteritis. 
 Their isolation is not thought to be as necessary as that of persons 
 suffering from the choleriform disease; we, therefore, observed only 
 seven cases in 1899 and two in 1900. 
 
 The author undertook some bacteriological investigations upon his 
 patients. 1 Information furnished by direct examination is generally of 
 little importance. In no instance have I found amebse. On the 
 other hand, the microscope revealed a more or less marked number 
 of microbes, some of which were round, others in the form of rods. 
 
 1 Roger. Recherches bacteriologiques sur l'ent6rite dysent£riforme. Presse meYlicale, 
 January 3, 1900. 
 
INFLUENCE OF INFECTIONS UPON THE ORGANISM. l-l 
 
 In slight cases the tnicrobic forms were quite numerous. In \ 
 cases one type predominated, viz., a quite large rod, resembling by 
 its form and size the bacillus of anthrax, bu1 differing from it \>y 
 its rounded extremities. H measured 5/< to 6/< in length and I '■'•." 
 or 1.5// m breadth. The cultures prepared with the mucu 
 the dysenteriform discharges likewise revealed uumeroui microbic 
 varieties in slight cuscs and predominance of certain bacilli in g 
 ones. 
 
 In the presence of these mierobie, wiriHie- no definite conclusion 
 could be drawn. I therefore resorted to the method of inoculation 
 
 Fig. 36, 
 
 Bouillon culture of bacilli found in dysenteriform enteritis (five hours old). 
 
 of the cultures into animals. After a sojourn of twenty-four hours 
 in the incubator the bouillon sown with intestinal mucus was 
 injected, into rabbits by the intravenous route in the dose of half a 
 cubic centimeter. All the animals succumbed, most of them in less 
 than twenty-four hours. "When a small drop of blood was examined 
 under the microscope a variable number of bacilli were seen which 
 were at times slightly encapsulated. It would seem as if the animal 
 had died of anthrax. In fact, the bacilli are quite large. They 
 measure in the blood from 5« to 6« in length and 1.3 « to 1.5 ft 
 in breadth. These microbes, however, can readily be distinguished 
 from the bacillus anthracis by the following characters: They 
 
 31 
 
482 
 
 INFECTIOUS DISEASES. 
 
 are not as long, and are at times so short as to be liable to be 
 mistaken for micrococci; they are decolorized by Gram's method 
 and rounded at their extremities ; finally, some present a constriction 
 at their middle part ; in the latter instance the extremities are oval, 
 hence the appearance is that of a diplococcus. When the bacillus 
 divides at the constricted point each part simulates a micrococcus; 
 but these newly formed elements soon become elongated and assume 
 the characteristic form. 
 
 Cultures succeed in all of the usual nutrient media. For instance, 
 a bouillon culture becomes turbid at the end of four or five hours. 
 
 Fig. 37. 
 
 Same culture (forty-eight hours old). 
 
 If it is examined at that time (Fig. 36) numerous rods measuring 
 4// to 6// in length and 1// in breadth are found; others are in pairs 
 measuring 3// to 3.5// by l/£. On the following days (Fig. 37) the 
 microbes are more slender and measure mostly 2// or 3// by 0.8/a 
 Culture on vegetables has a different appearance. (Fig. 38.) 
 The bacilli are more slender and generally shorter and mixed with 
 oval elements, often agglutinated by a viscid substance which renders 
 staining very difficult. The elements measure 0.75// to 1// in length, 
 1.25// to 0.5// in breadth. 
 
 This bacillus is motile, stains readily, but is decolorized by Gram's 
 method. The results obtained upon animals show that it possesses 
 
INFLUENCE OF INFECTIONS UPON THE ORGANISM, !-.; 
 
 a marked predilection for the large intestine; even when injected 
 through the veins it localizes itself in the terminal pari of the 
 digestive; true.!,. 
 
 The liver exercise:-; a destructive action upon this bacillus when 
 the culture is very young i. <■., while il contain very little, if any, 
 toxin. Animals inueiilaieil under these conditions through the 
 portal vein readily withstand doses which are fatal when injected 
 by the peripheral veins, in mosl instances destruction of the 
 bacilli is complete. In two cases, however, their \,\(~<-wc<- induced 
 hepatic abscesses. The pyogenic properties a1 times manifested by 
 
 Kir;. 38. 
 
 Culture on carrot (twenty-four hours old). 
 
 this microbe explain this result: it is to be noted, however, that 
 this is not an event of common occurrence. Having injected various 
 pyogenic microbes, such as the staphylococcus aureus, strepto- 
 coccus, and colon bacillus, into thirty-three rabbits by the portal 
 vein, I have in no case obtained similar results. 
 
 In view of the constant presence of the microbe in the cas a 
 examined by me and the effects produced upon animals. I am in- 
 clined to consider it as the cause of dysenteriform enteritis. This 
 opinion is further supported by the fact that I have not been able 
 to find the same agent in the stools of healthy individuals or of 
 patients suffering from choleriform enteritis. 
 
484 
 
 IXFECTIO US DISEASES. 
 
 It may, therefore, be asked whether my microbe represents a new 
 species. In examining the numerous works published on dysentery 
 I have found but two bacteria which may be compared with mine. 
 One of them is described by Ogata; the other, which has several 
 times been encountered in dysentery, is identified with proteus 
 vulgaris. 
 
 Ogata's bacillus 1 is pathogenic for the mouse, the guinea-pig, and 
 the cat; like mine, it liquefies gelatin. It differs clearly, however, 
 in that it stains by Gram's method. Its morphology is not identical ; 
 
 Proteus vulgaris. Culture upon carrot (twenty-four hours old). 
 
 the author describes it as a slender rod comparable to the tubercle 
 bacillus. 
 
 As regards the proteus vulgaris, it has frequently been met with 
 in patients suffering from gastroenteritis or even dysentery. The 
 morphological and biological characters are not identical; there are, 
 nevertheless, some obvious analogies — liquefaction of gelatin, fetid 
 odor, same action upon milk, glucose, saccharose, etc. The dif- 
 ferences are, however, sufficiently clear to prevent confusion. 
 Proteus vulgaris hardly develops upon slices of artichoke, the color 
 of which it does not modify. Our microbe forms upon this medium 
 
 1 Ogata. Zur Aetiologie der Dysenteric Centralblatt f. Bakt., 1892, Bd. xi., S. 246. 
 
INFLUENCE OF INFECTIONS UPON TEE ORGANISM. i-., 
 
 a yellow mass, while the remainder of the medium assume* a col( r 
 of intense green. The surface of the nutrient medium rapidly 
 becomes green when agar-agar prepared with artichoke water i 
 employed. The proteus vulgaris doe not develop in the latter 
 medium. The culture of my microbe upon carrots is while, quite 
 thick; that of the proteus vulgaris is scanty, consisting of very long 
 filaments and rods, intensely stained. I Fig. 39.) When this appear- 
 ance is compared with thai furnished by my bacillus (Fig. 38), the 
 non-identity of (he I. wo bacilli becomes manifest beyond all doubt. 
 
 Serum reaction furnishes another distinctive character. I em- 
 ployed the scrum derived from animals which had received a virulenl 
 culture of my bacillus by a branch of the portal vein and which had 
 resisted this inoculation. By putting one drop of this serum in 
 ninety-nine drops of a culture twenty-four hours old, agglutination 
 of the bacillus is obtained in a few minutes. The proteus is not 
 agglutinated, even when a tenfold amounl of the serum is employed. 
 
 My microbe has been encountered by Dr. Lemoine under similar 
 conditions, viz., in the course of an epidemic among soldiers house. 1 
 in the ficole Militaire. He isolated the bacillus in thirteen a 
 and found it to be pathogenic for animals. Finally, I h. Barl >ier told 
 me he had found, with the assistance of Dr. Tollemer, a bacillus 
 analogous to mine in an epidemic which appeared in the Hopital 
 des Enfants Malades. These authors practiced inoculations upon 
 rabbits and found intestinal ulcerations in a certain number of them. 
 In one case, in which they inoculated the virus into veins of the ear, 
 they discovered small abscesses in the liver containing the same 
 bacillus. 
 
 Influence of Infectious Diseases upon the Liver. 
 
 Microbes may reach the liver by various routes. They sometimes 
 spread through contiguity: they thus invade the gland as a result 
 of perihepatitis or even pleurisy. More frequently they follow one 
 of the circulatory systems ramifying in the organ: the portal vein, 
 the hepatic artery, and the lymphatic and biliary vessels. In almost 
 all infections, but more particularly in those which tend to directly 
 involve the intestines, such as typhoid fever, the liver is usually 
 altered. In dysentery the amebic find their way into its depths 
 in company with other parasites which cooperate powerfully to 
 induce suppuration. The hepatic artery is. in this connection, of 
 less importance: it is through it. however, that septic emboli reach 
 
486 INFECTIOUS DISEASES. 
 
 the liver, especially in cases of ulcerative endocarditis. The possi- 
 bility of hepatic infection through the lymphatic vessels has not 
 yel been well investigated. Hayem and some other authorities 
 think syphilitic sclerosis of the liver is induced through the lymphatic 
 channels. Microbes may likewise pass from the intestine to the 
 liver by way of the biliary channels; thus are produced angio- 
 cholites and, consecutively, biliary lithiasis. 
 
 The liver is very often affected in the fetus. During intra-uterine 
 life the individual is in relation with the external world by the 
 umbilical vessels, and it is through them only that pathogenic germs 
 can invade its organism; the microbes must, therefore, pass first to 
 the hepatic gland, which may sometimes arrest them and be sub- 
 jected to their action. In case infection becomes generalized the 
 liver is the organ most profoundly affected, as is notably the case 
 in syphilis and tuberculosis. What has been stated concerning 
 figurate elements is equally true as regards toxins, which are also 
 capable of producing disturbances and more or less pronounced 
 lesions in the liver. Moreover, this gland must neutralize autogenic 
 toxins produced in excess by diseased tissues and incompletely elim- 
 inated by the injured kidneys. 
 
 General Characters of the Infected Liver. In spite of its func- 
 tional disturbances, the liver may appear sound under macroscopic 
 and even microscopic examination. More frequently, however, it 
 presents various alterations. These may be divided into two groups : 
 some are specific, such, for instance, as syphilomata, tubercles, and 
 nodules of glanders. Others are ordinary lesions, and may be encoun- 
 tered in the majority of infections. They are characterized by con- 
 gestion, degenerations, cellular proliferations, ending at times in the 
 formation of small nodules. The macroscopic appearances of the 
 liver generally depend upon congestion and cellular degenerations. 
 
 The infectious liver is, as a rule, enlarged and soft, the latter 
 character being the more pronounced the more rapid the evolution 
 of the disease. Its color varies according as congestion or degenera- 
 tion dominates. In the former instance the liver is red; such is the 
 case in typhoid fever, in the first days of eruptive fevers, in cholera, 
 and acute intermittent fevers. When degeneration is predominant 
 the liver is pale, yellowish, anemic, at times covered with ecchy- 
 moses, which may be more or less extensive. 
 
 When the infectious liver is examined at an advanced period, two 
 orders of cellular lesions are found: degenerations of the hepatic cells 
 
INFLUENCE OF INFECTIONS UPON THE ORGANISM. i-7 
 
 and accumulation of round cells. The celli well, compre the cap- 
 illaries, and obliterate their lumina ; the initial congestion i folio 
 hy anemia. The cells are swollen and, al leasl in the beginning, 
 contain several nuclei and presenl fine karyokinetic figure . I 
 subsequently undergo hyaline and vitreoui degeneration, ac i ob-' 
 served particularly in typhoid fever and cholera, [n rarer instance 
 the process is characterized by coagulation necro i . by transforma- 
 tion of the cells into a vitreous mass withoul any colorable nucleus, 
 This process is localized and of less importance; it u the death of 
 the cells. Reactionary phenomena are coincidently produced which 
 account for proliferation of the nuclei. Fatty degeneration is very 
 rare; it occurs only in diseases of long duration, in chronic suppura- 
 tions, in which it is explained by diarrhea and cachexia of the 
 patients. The biliary channels at the same time undergo prolifera- 
 tion and newly-formed canaliculi appear, which are especially ma 
 in subacute forms. 
 
 The interstitial lesions consist in the formation of infectious 
 nodules (Friedreich, Wagner, Weigert, Hanot, Legry). These are 
 rounded, oval, or triangular in shape, and occupy any point of the 
 lobule, filling about one-twentieth part of it. They are formed of 
 masses of round cells contained in a granular substance; around 
 them the hepatic cells have suffered granulofatty degeneration. The 
 cells constituting them are probably of various origin; leucocytes, 
 cells of the interstitial tissue, probably also altered hepatic cells con- 
 tribute to form the masses. Finally, instead of being united in the 
 form of nodules, the cells may be distributed so as to form inter- 
 lobular or intralobular bands — a true embryonal cirrhosis which may 
 subsequently develop into chronic sclerosis — well studied by Hanot 
 and his disciple, Gaston. 
 
 Semiology of Infectious Liver. There is no method enabling the 
 physician to determine during life the functional value of the liver. 
 To this end rather crude procedures and indirect means are employed. 
 For instance, the size of the organ is taken as a basis. It is not 
 possible, however, to establish a relationship between atrophy or 
 hypertrophy of the liver and its function. It is better at times to 
 judge the state of this organ by disturbances observed in other parts 
 of the economy. These disturbances are of two orders. Some, 
 probably of reflex origin, are expressed by pulmonary congestion 
 localized at the right base and a bruit de galop of the right heart. 
 The others, more important, are of toxic origin. Delirious or coma- 
 
488 INFECTIO US DISEASES. 
 
 tose, even convulsive, manifestations may occur. The functions of 
 the kidneys, however, are more disturbed than the nervous system. 
 Hepatic inadequacy results in renal inadequacy, as expressed by 
 decreased secretion. At the same time, in consequence of disorders 
 induced by the hepatic disturbances in organic metabolism, urea is 
 diminished, the extractive matters are increased, and abnormal sub- 
 stances, such as albumin, peptones, etc., appear, and what is more 
 peculiar to hepatic disorders, various pigments, normal or modified 
 biliary pigments, and urobilin are present in the urine. 
 
 Icterus is quite rare in the course of infections and, when present, 
 is of rather unfavorable prognostic significance. In a large number 
 of cases, however, it is of a simple catarrhal nature, and does not 
 render prognosis any more serious. Some authors believe this catar- 
 rhal icterus is due to the fact that the bile is more viscid and is 
 partially retained; others assert that there is polycholia. 
 
 In certain instances the symptoms assume the type of those ob- 
 served in the course of grave icterus. This has occurred in cholera, 
 scarlatina, and typhoid fever; the cellular alterations are so intense 
 that autointoxication by hepatic inadequacy is produced. 
 
 Action of Infections upon the Pancreas. 
 
 The difficulty of recognizing disorders and lesions of the pancreas 
 during life and its rapid putrefaction after death have greatly hin- 
 dered its study. In spite of important works, among others those 
 of Carnot 1 and Klippel, we are in possession of no sure symptoms 
 enabling us to determine the part taken by the pancreas in infectious 
 processes. 
 
 The pancreas may be affected in the course of general infections, 
 such as measles, variola, pneumonia, septicemias, and pyemias. 
 Pancreatitis may also occur in ententes, typhoid fever, dysentery, 
 and cholera. The anatomico-pathological study, completed by ex- 
 perimental investigations, has revealed a whole series of lesions from 
 diffuse to hemorrhagic and suppurative pancreatitis. These lesions 
 may be repaired. In many instances, however, as in the case of the 
 liver, they become the starting point of scleroses, and may subse- 
 quently end in cirrhotic atrophy of the gland. Pancreatic diabetes 
 is probably thus engendered. 
 
 1 Carnot. Recherches experimentales et cliniques sur les pancreatites. These de 
 Paris, 1898. Richardiere and Carnot. Maladies du pancreas. Traits de m6decine et 
 de therapeutique, Paris, 1898, t. v., p. 9. 
 
INFLUENCE OF INFECTIONS UPON THE ORGANISM. |.-:. 
 
 It is well to remark that sclero i may occur in the absence of .''II 
 infection of the gland under the influence of toxin engendered in 
 other parts of the organism. Dr. Carnol ha de cribed .'i tubercular 
 sclerosis of the pancreas w hicli may be compared with similar scle- 
 roses developing in oilier organs and Qotably thyroidian sclero 
 
 Influence of Infections upon the Kidneys. 
 
 The study of renal lesions in the course of infectious di 
 comparatively easy, since examination of the urine, especially search 
 for albumin and casts, enables us to appreciate the functional con- 
 ditions and lesions of the kidneys. 
 
 All infections, even when benign and localized, may give rise to 
 renal alterations. Pneumonia and the various pneumococcic infec- 
 tions produce diffuse nephritis remarkable for the frequency of 
 hematuria. Cholera induces renal lesions which seem to play an 
 important r61e in the pathological physiology of this malady, and 
 explain certain symptoms. Syphilis and tuberculosis give rise to 
 acute or chronic processes. 
 
 Among infectious diseases scarlatina causes the most interesting 
 renal phenomena. Albuminuria is frequent, appearing at times dur- 
 ing the stationary period, and in other cases during convalescence. 
 It was absent in only one of the author's cases ending fatally — such 
 fatal cases constituting 53 out of a total of 2157 scarlatina cases. 
 Scarlatinal nephritis is generally considered to be of little gravity. 
 It is true that even when it gives rise to uremic phenomena, recovery 
 is possible. Besides the 53 cases above mentioned, the author's 
 statistics show 663 other patients in whom scarlatina was compli- 
 cated by albuminuria, and who recovered. It is important to note, 
 however, that although the acute symptoms subside far more readily 
 in scarlatinal nephritis than in all other varieties, the patient incom- 
 pletely recovers. Nephritis too often passes into a chrome state 
 either because albuminuria persists or because it reappears on the 
 slightest occasional cause. 
 
 The researches of Ponfick, Langerhans, Wissokovitch, Biedl, and 
 Kraus have demonstrated that microbes introduced into the blood 
 are rapidly eliminated by the urine. In certain instances the excre- 
 tion of bacteria begins at the end of fifteen or twenty minutes. 
 Their passage is often effected without any injury to the kidneys. 
 It is intelligible, however, that, according to the degree of virulence 
 of the germs and the vulnerability of the organ, colonization may 
 
490 IXFECTIO US DISEASES. 
 
 occur, the microbes being there arrested and producing poisons 
 which prove the starting-point of nephritis. In other instances the 
 toxins are brought to the renal glands from other points of the 
 economy. The role of the kidne}^ in the elimination of poisons 
 accounts for the frequency of lesions which these organs suffer in 
 the course of infectious diseases. 
 
 Influence of Infections upon the Genital Organs. 
 
 Orchitis complicating mumps is never observed in children; it 
 occurs only in adults, following localization in the parotid glands, and 
 at times replacing it as a sort of metastasis. In rare cases orchitis 
 develops coincidently with parotiditis, and in exceptional instances 
 it represents the -first and even the only manifestation of the disease. 
 The testicular inflammation lasts four or five days, and never ends 
 in suppuration. Were it not for the danger of tardy atrophy of the 
 testicle, the involvement would be of no gravity whatever. When 
 both testicles are involved prognosis must be reserved from a pro- 
 creative standpoint. 
 
 Typhoid fever has been cited among infections particularly liable 
 to affect the testicles. According to Chantemesse, orchitis occurs in 
 the proportion of 1 to 196 cases; it subsides in ten or twelve days 
 without causing atrophy of the gland. In some cases, however, 
 owing to localization of the typhoid bacillus, suppuration remarkable 
 for its long duration has occurred. 
 
 The ovaries are less frequently involved than the testicles; their 
 participation has, however, been noted in typhoid fever, variola, and 
 mumps. Like other parts of the organism, the uterus may be 
 affected in measles, variola, and typhoid fever. 
 
 Influence of Infections upon Menstruation. The relations between 
 menstruation and the development of erysipelas have long been 
 noted. We must leave aside those instances in which the coincidence 
 is accidental. For instance, one of our patients had already had 
 six attacks of erysipelas; the seventh attack occurred with menstrua- 
 tion. Genuine menstrual erysipelas always occurs on the occasion 
 of menstruation. These erysipelas attacks are generally so benign 
 as to cause no anxiety, and, therefore, few patients resort to the 
 hospitals. We have observed but 16 such cases out of a total of 
 1198 erysipelatous women. One of them had had forty-six attacks, 
 always coincident with menstruation. 
 
INFLUENCE OF INFECTIONS iros THE ORGANISM \w\ 
 
 Erysipelas may al times replace the men trual flow. A woman 
 twenty-one years of age had had her firi I eryi Ipelai eleven months 
 before; since that time Bhe had six more attacks, and each time the 
 cutaneous inflammation appeared the catamenial discharge failed to 
 occur. She entered the hospital on March 17th for a quite in 
 erysipelas replacing menstruation. On April Llth, while she was 
 still in our wards, the incuses appeared in a regular manner, and 
 erysipelas did riot recur. 
 
 In three oilier cases erysipelas recurred regularly every month 
 before puberty, and, at this period the cutaneous manifestation* 
 ceased or persisted. A woman, forty-five years of age, told the 
 author that from the age of seven years to thai of eighteen she had 
 every month developed a slight erysipelas; at the age of eighteen 
 menstruation was established and the periodical erysipelatous attacks 
 ceased. She had one attack of erysipelas at the age of thirty-two 
 years, occurring independently of the menses. The menopause 
 occurred at the age of thirty-eight years, and from that time on. 
 while she has had no menstruation, she experienced two attacks of 
 erysipelas, once when forty-one years old, and another for which she 
 resorted to our wards, at the age of forty-five years. 
 
 Of all infectious diseases variola is undoubtedly the one which 
 most frequently causes menstrual disturbances. Uterine hemor- 
 rhages are observed in 11 or 12 per cent, of the cases which recover. 
 Metrorrhagia generally occurs at the period of invasion; in some caa a 
 during convalescence. The action exercised by variola upon the 
 uterus is so marked as to cause bloody discharges even after the 
 woman has reached the menopause. This occurred in a patient 
 forty-five years of age, in whom the menopause had been established 
 six months before. The same happened in a twelve-year-old child 
 who had not yet begun to menstruate. The author has observed 
 the same even in a child five months old. 
 
 Menstrual disturbances are particularly frequent in fatal cases of 
 variola. Metrorrhagia complicates 28 per cent, of confluent variola: 
 it is never absent in hemorrhagic variola. 
 
 According to our statistics, measles gives rise to premature men- 
 struation in 5 per cent, of the cases and scarlatina in 10 per cent. 
 
 Influence of Infections upon Pregnancy and Lactation. It seems 
 to the author that the gravity of infections in pregnant women has 
 been somewhat exaggerated. In this connection erysipelas has been 
 a special subject of study. Clinicians had long since noted the 
 
492 INFECTIO US DISEASES. 
 
 remarkable relationship existing between erysipelas and puerperal 
 fever. Bacteriological researches have shown that the same microbe 
 is concerned in both instances, and thus have confirmed the data of 
 observation. The facts, however, which the author has collected do 
 not justify thefears of accoucheurs regarding erysipelatous infections. 
 
 The author will first consider the influence of erysipelas upon the 
 course of pregnancy. Ancient authors dwelt much upon the fre- 
 quencjr of abortions: Wardevell saw 24 abortions out of 25 cases. 
 Recent statistics are far better : Duchein gathered 41 cases, and notes 
 but 14 abortions. Dr. Legendre observed 4 abortions in a total of 
 13 cases. The author has received 44 pregnant women into his 
 wards. In 25 of these, although several suffered from grave ery- 
 sipelas, pregnancy continued its course. Nineteen, twelve of whom 
 had reached full term, were confined in our wards; the other con- 
 finements took place in the seventh or eighth month. 
 
 Erysipelas of the mother does not seem to be dangerous for the 
 child. All those which were born at full term survived and developed 
 well. Only one of them contracted the disease. 
 
 Suckling by Infected Women. Shall an infected woman be allowed 
 to suckle? This question is to be answered according as infection is- 
 protracted or transitory. In the former instance suckling must be 
 interdicted; such is the rule as regards typhoid fever. In the case 
 of transitory infections suckling may be permitted. 
 
 In view of the evil effects of artificial feeding among the poorer 
 classes, the author first permitted erysipelatous women to suckle 
 their children. No harm resulting, he followed the same rule in other 
 infections treated in his wards. The result seemed to be highly 
 gratifying. Out of a total of over 100 children, only two were in- 
 fected; one of them contracted measles, the other erysipelas from 
 the mother. In both instances, however, the evolution was remark- 
 ably benign. The other children presented no disturbance. It is to 
 be remembered that infection diminishes the lacteal secretion and 
 may necessitate mixed feeding for a few days. Only in very grave 
 cases of variola is the secretion so profoundly altered as to render 
 suckling impossible. 
 
 The rules are well defined as regards syphilis. It is important that 
 the mother should suckle her child. The laws of Colles and Profeta 
 show that there is not the slightest inconvenience in this practice. 
 If either of them, the mother or the offspring, is alone contaminated, 
 the disease is not transmitted to the other. 
 
INFLUENCE OF INFECTIONS urns TEE ORGANISM. !!».", 
 
 As regards hilxTculosis, the rule is the reverse of the preceding. 
 Suckling must be forbidden. Not because the milk i <■ dan- 
 gerous — Koch's bacillus very seldom passes into the milk bul in 
 the course, of this chronic disease the milk Is of an inferior quality 
 and, on the other hand, it is wise to diminish the chances of con- 
 tagion by limiting the contact between the mother and her child. 
 
 To sum up, while suckling is to be forbidden in chronic infections, 
 except syphilis, or in prolonged acute infections, il may I"- permitted 
 in other cases. 
 
CHAPTEE XVII. 
 EVOLUTION OF INFECTIOUS DISEASES. 
 
 Incubation. Duration of Incubation in Principal Infections. Invasion. Stationary 
 Period. Course of Local and of General Phenomena. Clinical Forms. Clinical 
 Forms of Pneumonia and of Typhoid Fever. Termination of Infectious Diseases. 
 Defervescence. Crises. Urinary and Urotoxic Crises. Study of Urinary Crises in 
 Pneumonia, Erysipelas, Scarlatina, and Catarrhal Jaundice. Convalescence. Acci- 
 dents of Convalescence. Relapses and Recurrences. Passage of Acute Infection 
 into a Chronic State. Death. Death by Mechanical Cause. Death by Intoxica- 
 tion. Death by Post-infectious Cachexia. 
 
 The evolution of infectious diseases may be divided into four 
 periods or stages: incubation, invasion, stationary period, and de- 
 cline. 
 
 Incubation corresponds to the time elapsing between the deposi- 
 tion of a pathogenic agent in the organism and the first appearance 
 of morbid manifestations. Invasion, which indicates the beginning 
 of the disease, may be abrupt or insidious. In the former instance, 
 the moment at which the disease sets in may be noted in a precise 
 manner. Such is the case, for instance, when an apparently healthy 
 individual is suddenly seized with a violent chill. The passage from 
 a sound into a morbid state occurs without transition, and is sharply 
 defined. In other cases the symptoms develop gradually, so that an 
 intermediate period of malaise or indisposition elapses, and it is then 
 very difficult to determine the beginning of the disease. The devel- 
 oped disease remains for a certain time stationary, presenting more 
 or less marked oscillations of aggravation and amelioration; this is 
 the stationary period. Then comes the decline which, like invasion, 
 may be sudden or progressive. In the former case, a sudden defer- 
 vescence or crisis is said to occur, and the expression decline is 
 reserved for the slow course toward recovery. 
 
 After the favorable termination of the disease there remains a 
 period, at times of considerable length, during which the functions 
 are re-established progressively, and gradually become normal. This 
 is convalescence. 
 
 Finally, even when the morbid acts seem to be terminated, the 
 organism may not have completely resumed its former mode of life. 
 
EVOLUTION OF INFEOTI0U8 DI8EA8E8. !!•., 
 
 Certain anatomical changes or functional disturbance* may pei 
 remaining inappreciable even on profound examination; buf s Bilent, 
 insidious, morbid evolution continues which terminate* a1 the end of 
 several years in symptoms, disorders, and affection* which are not 
 readily traced to their origin. 
 
 Such are the various periods observable in the course of infect 
 discuses. This division is appreciable, especially when evolution fol- 
 lows an acute course. If is far less definite in ca e of chronic 
 infection. 
 
 Moreover, the morbid evolution may be constantly modified by 
 
 some unexpected event, or complication, or i1 may be interrupted 
 
 by death. 
 
 Incubation. 
 
 Incubation, as above stated, is the time elapsing between the depo- 
 sition of the morbid germ in the tissue and the appearance of the 
 first local or general symptoms of the disease. This definition, which 
 is applicable only to neuroinfections, must be slightly modified when 
 the process is one of autoinfection. In the latter case the germ is 
 not deposited in the organism from without, and therefore the st. •!<:<' 
 of incubation begins at the moment when the dormant microbe, 
 until then inoffensive, becomes pathogenic under the influence of 
 some excitation. It is intelligible that if the determination of the 
 period of incubation is a matter of difficulty in the former case, it 
 is almost an impossibility in the latter. 
 
 During the period of incubation the organism does not always 
 remain passive; it may endeavor to destroy the invading microbes. 
 Should it fail to do this, the disease becomes manifest. It is there- 
 fore incorrect to say that an infectious disease is a reaction aroused 
 by the introduction of a microbic agent, since morbid reaction does 
 not necessarily occur in all instances. The microbe may be de- 
 stroyed or remain quiescent at the point where it was de] >< sited. In 
 order that morbid manifestations may appear, a period of prepara- 
 tion is required which represents a first defeat of the organism. ^ e 
 are thus led to admit the occurrence of three successive stages at the 
 beginning of all infections : introduction or exaltation of the microbe, 
 a latent period of development corresponding to incubation, and a 
 reaction of the organism corresponding to invasion, that is. to the 
 beginning of the disease. 
 
 The period of incubation may be silent and unattended by morbid 
 manifestations; then, at a given moment, a reaction is produced, 
 
496 INFECTIOUS DISEASES. 
 
 often quite suddenly. Such, for instance, is the beginning of lobar 
 pneumonia. It is a very curious fact that the microbe should be 
 able to continue secreting its toxins in a progressive manner without 
 giving rise to any disturbance on the part of the organism, and that 
 the organism should act so tardily when it is, as it were, saturated 
 with soluble toxic products. 
 
 Even when the beginning is sudden it is often difficult, if not 
 impossible, to determine the period of incubation, since we are not 
 always able to decide as to the moment when contagion occurred. 
 Most frequently patients are unable to give an}^ information. In the 
 eruptive fevers, except variola, it is seldom possible to determine 
 under what conditions contamination has taken place. Even when 
 patients know that they have been in contact with an infected person 
 they do not remember with accuracy the day on which they saw the 
 diseased individual. Others have passed several days at the bedside, 
 and it is evidently impossible to know at what moment contamina- 
 tion was effected. Finally, in cases of prolonged incubation, it may 
 always be asked whether a later contamination which has remained 
 unnoticed has not taken place. Consequently, in order to reach 
 unassailable results, a series of circumstances are required which are 
 seldom realized. The perusal of works on incubation leads to the 
 conviction that an average duration, varying only within narrow 
 limits, exists for the majority of diseases. It would be a grave error, 
 however, to overlook the fact that the period of incubation is at 
 times shortened and at other times prolonged within considerable 
 limits. Nothing in this regard is more demonstrative than the his- 
 tory of venereal diseases, for it is in this class of affections that the 
 moment of contamination may be determined most exactly, and that 
 interpretation is easiest. With syphilis, for example, the chancre 
 generally makes its appearance from twenty to thirty days after 
 infecting intercourse. This average, which is sufficiently wide in its 
 scope, does not, however, include those cases in which the beginning 
 is manifest at the end of ten days, nor those in which it is delayed 
 until the fortieth or even fiftieth day. The variability of this period 
 is proved by the fact that several indurated chancres resulting from 
 a single infection may appear successively in the same individual 
 at intervals of several days. The same variations are observed in 
 gonorrhea. The average is from two to five days, but the discharge 
 sometimes sets in after twenty-four hours or appears very tardily at 
 the end of several weeks. In the latter instance it is assumed that the 
 
EVOLUTION OF INFECTIOUS DISEASES. 407 
 
 microbes deposited in the balanopreputial furrow have n' »i invaded 
 the urethra until a certain time ofter coitus. With the Bofl chancre 
 incubation is more fixed and does no1 exceed twent) four ho 
 This figure is confirmed by numerous inoculation! practised upon 
 subjects presenting suspicious ulcerations. 
 
 [nformation is quite precise in ca e of infection of traumatic 
 origin. In the case of tetanus the period of incubation is from two 
 to three days; iii the statistics of the civil wax in Americi 
 find that in twenty-seven cases the aymptome appeared on the 
 day of traumatism. Bertran (of Elbeuf) has seen tetanut appear five 
 hours after the infection of the wound. It has been stated thai 
 incubation at times lasted only two hours. On the other hand, \i 
 has in some eases been prolonged thirty and thirty-five da] 
 
 In hydrophobia the incubation period is still more variable, the 
 average being thirty days and the minimum fourteen. As to the 
 maximum, a period of eighteen months has been admitted, although 
 there are certain rare instances in which the period of incubation 
 lasted two, three, and even four years. Erysipelas may be considered 
 as occupying a position between traumatic diseases and those appar- 
 ently spontaneous. Most of the classic treatises fix its period of 
 incubation at three or four days, admitting that it may be reduced 
 to two days or prolonged to twelve. Leaving aside the cases of non- 
 traumatic erysipelas, the beginning of which cannot be determined 
 with accuracy, let us consider the results obtained in eases in which 
 streptococcic infection developed in a wound. In eighty-three cases 
 we obtained accurate information permitting us to fix the time 
 elapsing between the accident and the beginning of the infection. 
 The figures are as follows: 
 
 Incubation period from 
 
 3 hours 
 
 1 
 
 observation. 
 
 7 to 18 " 
 
 11 observations. 
 
 24 " 
 
 14 
 
 " 
 
 2.5 to 48 " 
 
 11 
 
 " 
 
 40 to 72 " 
 
 9 
 
 '* 
 
 4 to 5 day~ 
 
 s 
 
 •• 
 
 6 to 8 " 
 
 16 
 
 •• 
 
 9 to 15 " 
 
 17 
 
 ■• 
 
 111 twelve cases incubation was. as we see. extremely short: not 
 the slightest doubt may be entertained as to the evolution, the 
 details of the facts being given. Here is. for example, one of them: 
 
 The wife of a physician was preparing to go to a ball. Inputting 
 on her ear-rings, which she had not worn for a long time, she pro- 
 
 32 
 
498 INFECTIOUS DISEASES. 
 
 duced a slight abrasion in the ear. This occurred at 9 p.m. On her 
 return home, at 4 a.m.. she was taken with a violent chill, fever set 
 in. and her husband noticed in the morning the development of a 
 typical erysipelas. General reaction was, therefore, produced seven 
 hours after traumatism. 
 
 When erysipelas develops tardily it may be questioned whether it 
 is truly a case of prolonged incubation, since it is possible that the 
 wound may be infected later and that the streptococcus may not 
 have been introduced at the moment of the accident. We must 
 acknowledge that the problem cannot be solved by clinical obser- 
 vation alone. Experimentation must, therefore, be resorted to. If 
 we inoculate a culture of streptococcus beneath the skin of the ear 
 of a rabbit, erysipelas develops generally within twenty-four or forty- 
 eight hours. At times the incubation lasts three or four days. In 
 two cases the author has seen it prolonged eleven days. Here, there- 
 fore, are results of considerable practical consequence. They confirm 
 what is taught by clinical observation and establish that in erysipelas 
 incubation may last only a few hours or exceed a week. But what 
 must we think of the cases in which the period of incubation lasts 
 fifteen or even twenty-two days? All hypotheses are permitted. 
 When, however, the wound does not seem to have been contaminated 
 ulteriorly, we may assume that it was infected as soon as it was 
 produced, whether the microbe proceeded from the soil or from 
 the skin of the patient. Later on some occasional cause, which may 
 often escape notice, favors the development of the dormant germs. 
 The influence of cold or a draught in such cases is thus explained. 
 We had a demonstration of this in several cases in which we saw a 
 recurrence under such influences. Patients who seemed to be com- 
 pletely cured of erysipelas left our wards, suddenly exposed them- 
 selves to cold, and in the evening of the following day the infection 
 reappeared and forced them to return to the hospital. In such 
 instances the microbes which still persisted in the skin were exalted 
 owing to transitory weakening of the tissues, occasioned by an auxil- 
 iary cause, however common this cause may seem to be. 
 
 There is another question. Is there any relation between the 
 duration of the period of incubation and the gravity of erysipelas? 
 Our observations compel us to answer in the negative. In one of 
 the patients who died the incubation period lasted eight days. In 
 two instances erysipelas was grave, followed a wandering course, and 
 was prolonged for three weeks. In one of these cases incubation had 
 
EVOLUTION OF INFECTIOUS DISEASES. ifiit 
 
 lasted twelve hours, in the other eighl days. On the other band, 
 we have seen ;i, slight erysipelas which la ted only four days and the 
 incubation period of which did no1 exceed thirty-five hours. In fact, 
 the duration of the period of incubation may be very short in two 
 quite different cases. At times evolution is grave, because the 
 microbe is highly virulenl anddevelopi withgreai rapidity. In other 
 instances, on the contrary, the phenomena appear speedily bee 
 the organism is capable of powerful reaction. In 1 hi case erysipelas 
 
 is of a more benign characlcr th.'in if (he incubation had lasted longer; 
 the germicidal serum and phagocytes arrive early and more easily 
 overcome the microbes which ;uv ;i I ready developed. The explana- 
 tion we propose is not a mere hypothesis; it is supported by experi- 
 mental data. We have shown, for example, that it is possible to 
 shorten considerably the period of incubation by sectioning the vaso- 
 motors distributed to the inoculated ear. Under these renditions 
 the responsive sensitiveness of the operated side is increased and 
 erysipelas develops more rapidly than on the normal side. But its 
 evolution is more prompt and favorable in so far as the lesions, which 
 are often observed in animals in consequence of the streptococcic 
 inoculation, do not appear. Thus, in cases in which the disease is 
 unavoidable it is desirable that it should begin early, since the 
 organism will then combat a smaller number of microbes and will be 
 less profoundly impregnated by toxins. 
 
 Among the eruptive fevers, precise information is most easily 
 obtained in smallpox. Its period of incubation is, on an averages 
 twelve days, but it may vary between seven and fifteen. In scarla- 
 tina, Sevestre finds an almost invariable average of four to five days, 
 but there are observations recorded in which the period of incuba- 
 tion lasted no longer than twenty-four (Trousseau), twelve (Seves- 
 tre), and even seven hours (Thomas). In other cases it has been 
 prolonged to twelve, seventeen, and forty days (Rilliet and Barthez). 
 In two instances reported by Dechambre it lasted seven weeks. It 
 is well to note that these extreme figures are altogether exceptional 
 and that an incubation period of from two to five days answers fairly 
 well to general facts. We have been able to establish the period of 
 incubation in twelve cases. In two of these it did not exceed twenty- 
 four hours. One of the two observations was very precise. It was 
 the case of a man who had seen a friend on his fifth day oi scarlatina. 
 On the following day he experienced fever and dysphagia, and the 
 next day the eruption appeared. The incubation period was forty- 
 
500 INFECTIO US DISEASES. 
 
 eight hours in six cases and three days in another. Finally, three 
 women manifested the first symptoms of scarlatina in sixty-eight, 
 seventy, and seventy-two hours, respectively, after having been 
 admitted as nurses to our scarlatina wards. In surgical and puer- 
 peral scarlatinas the incubation period may be very short, and 
 generally does not exceed three days (Paget, Sorensen). This may, 
 perhaps be explained by the fact that surgical or obstetrical trau- 
 matism diminishes the resistance of the organism. 
 
 The incubation period of measles is from eight to twelve days, 
 with a minimum of four and a maximum of fourteen. That of 
 rubeola is eighteen days, being sometimes prolonged to twenty or 
 twenty-one, and exceptionally falling to eight and even five days 
 (Griffiths). Varicella is said to begin fourteen to fifteen days after 
 contamination. At times it appears after the nineteenth day, but 
 never before the thirteenth. In two personal observations the 
 period of incubation seemed to be seventeen days. According to 
 Steiner, inoculated varicella begins on the sixth clay. 
 
 Of other infections the incubation period of which has been fairly 
 well determined, we may mention diphtheria, which begins two days 
 after contagion, and at times after seven and even fifteen days 
 (Sanne); and whooping-cough, from two to eight clays after. In 
 mumps the incubation period is generally fifteen clays. In three 
 cases published by Roth it was exactly eighteen days. In cholera 
 the beginning has at times occurred a few hours after contagion. In 
 other cases it has appeared on the sixth day. In typhus fever an 
 incubation period of twelve days is generally admitted, which may 
 at times be prolonged to twenty-three. The attack has at times 
 occurred almost instantly (Marsh, Netter). In such cases individuals 
 who approach a patient are deeply impressed by a disagreeable odor 
 and are immediately forced to lie down. The following table, which 
 indicates the average, maximum, and minimum incubation periods, 
 is based upon facts recorded by various authorities, upon statistics 
 published by Williams on behalf of a London commission, and upon 
 our own personal observations: 
 
EVOLUTION OF INFECTIOUS DISEASES. 
 
 601 
 
 
 
 
 
 Iniiiii iTIO 
 
 
 
 
 
 
 Avi riii/i 
 
 Minimum. 
 
 
 Iforimum 
 
 Anl hrax, 
 
 
 
 2 < 
 
 laj I 
 
 da 
 
 
 :'. 
 
 days. 
 
 Bubonic plague, 
 
 1 
 
 lo 
 
 8 
 
 " 2 
 
 • l:i 
 
 
 7 
 
 a 
 
 < Ihanore (soft), 
 
 1 
 
 lo 
 
 2 
 
 i 
 
 day 
 
 
 3 
 
 " 
 
 ( Iholera, 
 
 '2 
 
 to 
 
 1 
 
 I 
 
 " 
 
 
 8 
 
 " 
 
 l )iplii heria, 
 
 
 
 2 
 
 " 2 
 
 da 
 
 
 15 
 
 " 
 
 Erysipelas, 
 
 1 
 
 to 
 
 (i 
 
 3 
 
 hours 
 
 
 22 
 
 " 
 
 1 afluenza, 
 
 3 
 
 to 
 
 4 
 
 1 
 
 day 
 
 
 :. 
 
 " 
 
 < Handera, 
 
 3 
 
 to 
 
 r, 
 
 " 24 
 
 hours 
 
 
 3 
 
 IIIOIll I 
 
 < lonorrhea, 
 
 3 
 
 lo 
 
 5 
 
 I 
 
 (?) to 
 
 2 daj 
 
 l 
 
 '.il nreeks. 
 
 Mumps, 
 
 
 
 \r, 
 
 7 
 
 da ■ 
 
 
 30 
 
 flays. 
 
 Malaria, 
 
 6 
 
 lo 
 
 LO 
 
 " 99 
 
 noun 
 
 
 Several months, 
 
 Recurrent fever, 
 
 5 
 
 to 
 
 6 
 
 " 86 
 
 *t 
 
 
 S 
 
 days. 
 
 Measles, 
 
 
 
 9 
 
 •1 
 
 da] 
 
 
 14 
 
 a 
 
 1 [ydrophobia, 
 
 20 
 
 to 
 
 on 
 
 13 
 
 " 
 
 
 L8montb 
 
 Rubeola, 
 
 
 
 is 
 
 ft 
 
 " 
 
 
 21 
 
 days. 
 
 Scarlatina, 
 
 2 
 
 to 
 
 5 
 
 7 
 
 hours 
 
 
 7 
 
 v. eel 
 
 Smallpox, 
 
 
 
 12 
 
 7 
 
 days 
 
 
 16 
 
 
 Syphilis, 
 
 20 
 
 to 
 
 30 
 
 LO 
 
 " 
 
 
 50 
 
 " 
 
 Tetanus, 
 
 2 
 
 to 
 
 3 
 
 " 2 
 
 hours 
 
 
 35 
 
 " 
 
 Typhoid fever, 
 
 
 
 14 
 
 " 2 
 
 days (?) 
 
 21 
 
 " 
 
 Typhus, 
 
 
 
 12 
 
 i) 
 
 (?) 
 
 
 23 
 
 " 
 
 Vaccinia, 
 
 
 
 3 
 
 " 2 
 
 days 
 
 
 7 
 
 " 
 
 Varicella, 
 
 14 
 
 to 
 
 15 
 
 L3 
 
 " 
 
 
 19 
 
 " 
 
 Whooping-cough, 
 
 
 
 8 
 
 " 2 
 
 " 
 
 
 8 
 
 " 
 
 Yellow fever, 
 
 o 
 
 to 
 
 4 
 
 2 
 
 " 
 
 
 6 
 
 " 
 
 To the infections presented in the foregoing list we may add those 
 the microbes of which may remain for a long period of time in a 
 latent state in the organism. Such is the case in tuberculosis and 
 leprosy. The most extraordinary observation is that of Hallopeau : 
 An individual presented the first symptoms of leprosy thirty-two 
 years after having returned from a country where this disease is 
 endemic. 
 
 Clinical experience suffices to establish that the duration of the 
 incubation period is very variable, and experimental researches 
 have demonstrated certain causes which precipitate or delay the 
 beginning of a disease. First, there is an idea which should never 
 be lost sight of, that is, the variability in the action of viruses. 
 Viruses may be divided into two groups — i. e., fixed and variable. 
 In this regard nothing is so instructive as the history of hydrophobia. 
 The variable virus is that found in an animal which has accidentally 
 become rabid. The fixed virus is that which has acquired a deter- 
 mined degree of power by virtue of successive passages through ani- 
 mals. By inoculating the virus into animals of the same species 
 placed under the same conditions the phenomena are produced after 
 
502 INFECTIO US DISEASES. 
 
 the lapse of a perfectly determined period of time. Such is not the 
 case, however, in nature, and the constant variations in virulence 
 result in modifications in the period of incubation. The same result 
 is observed in man. By virtue of its transmission by successive 
 inoculations, vaccinia has become a fixed virus. Its period of incu- 
 bation is almost invariable. In subjects vaccinated for the first 
 time, the eruption appears seventy-two hours after inoculation, and 
 is well developed in the course of the fourth day. Even with this 
 fixed virus, however, certain variations are observed. 
 
 The soft chancre, which is transmitted by direct inoculation 
 just as is an experimental virus, has also acquired a sufficiently 
 fixed power. Hence, the lesion always begins twenty-four or 
 forty-eight hours after contamination. The occurrence of a longer 
 period of incubation must be attributed to inaccurate observa- 
 tion. 
 
 It can readily be understood that with viruses of variable potency 
 the greater the energy and number of microbes introduced the 
 shorter will be the incubation period. The period of incubation 
 will also vary with the location of the wound. It will be longer 
 if the affected region is provided with dense cellular tissue and is 
 poorly supplied with vessels and nerves. Such is strikingly the case 
 in hydrophobia. Finally, microbes develop more readily when 
 they are introduced simultaneously with irritating substances or 
 other bacteria, even simple saprophytes, favoring their multipli- 
 cation. 
 
 On the part of the organism all causes of weakening should be 
 taken into account — extensive traumatism, laceration of tissues, 
 modifications of the general condition by overexertion, excesses, 
 alcoholism, intoxications, and previous or present diseases. Lastly, 
 we must not overlook the influence of moral impressions, the power 
 of which is well known with respect to hydrophobia. For example, 
 an individual who has been bitten by a rabid animal no longer 
 thinks of his accident. Suddenly a word reminds him of the bite, 
 and immediately manifestations of the disease appear and rapidly 
 terminate in death. The duration of the period of incubation may 
 also be modified by the responsive aptitudes of the subject. In 
 persons with very sensitive nervous systems the onset will be 
 hastened. In this particular case a short period of incubation 
 constitutes a favorable phenomenon. 
 
EVOLUTION OF INFECTIOUS DISEASES. 503 
 
 Invasion. 
 
 Invasion may be sudden, or slow and progresi ive. In the former 
 instance the stationary period i quickly reached) in the latter il 
 supervenes only at the end of a f<-w days, and is thus preceded by 
 a prodromic period in which the symptom are inadequate to 
 determine the nature of the morbid proce 
 
 As an example of infection with sudden unci, writers alv 
 cite pneumonia, and, as an example of slow invasion, typhoid fever. 
 These two illustrations are well chosen. Clinical phenomena are 
 always so variable, however, thai a greal many exceptions may be 
 mentioned. There are cases of pneumonia beginning in a Blow and 
 insidious manner, and I here are typhoid fevere characterized by a 
 sudden onset. It is not difficult to understand how progressive 
 invasion is effected. The noxious substances are secreted little by 
 little by the microbes, become diffused in the organism, and influence 
 the cells. When the toxins are elaborated in greater amount their 
 constantly increasing accumulation gives rise to more and more 
 marked disturbances. A sudden onset is more difficult of explan- 
 ation. Even in pneumonia it is possible that the morbid poison is 
 secreted in a progressive mariner, and at first sight the sudden 
 appearance of the phenomena is not understood. The differences 
 are probably due to the mode of action of poisons. This view i-. 
 of course, purely hypothetical, but it is supported by some facts. 
 A first result which must be taken into account is that most microbic 
 toxins, unlike poisons properly so called, and notably alkaloids, 
 exert no immediate action. Even when they are introduced into 
 the blood no immediate symptom is produced, but after a period 
 of latency of varying duration the morbid phenomena suddenly 
 appear. This experimental fact has a very important bearing upon 
 our subject. In fact, it may be assumed that in certain cases 
 microbic poisons act clearly and rapidly as they are elaborated. 
 Under such conditions disturbances begin slowly and follow a pro- 
 gressive course. In other instances an oversaturation of the 
 organism will be required in order to produce reaction. This is the 
 first effect of cumulative doses. 
 
 Whatever be the mode of invasion, the general phenomena first 
 bear on the nervous system. If invasion is slow and progressive, 
 the disturbances are gradually intensified. These are malaise, head- 
 ache, dizziness, weakness of the extremities, and incapacity for all 
 
504 ISFECTIO US DISEASES. 
 
 muscular or mental exertion. Delirium, if present, is of the mild, 
 quiet type. Sleep is disturbed only by nightmares or some vagaries. 
 On the whole, the symptoms are not intense, and are established 
 gradually and aggravated in a slow, and often regular, manner. 
 On the other .hand, if invasion is sudden the nervous symptoms 
 will be intense and disquieting from the first. The process is of the 
 nature of a true outbreak. There has been a silent accumulation 
 of toxins, and all of a sudden a violent, impetuous, unexpected 
 reaction occurs — i. e., intense chills or, in children, a convulsive 
 attack. At the same time fever develops and rapidly reaches 
 102.2° or 104° F. (39° or 40° C). 
 
 Headache is intense, and delirium may be excessive from the first. 
 Severe delirious phenomena are mostly, we might say nearly always, 
 observed in diseases characterized by sudden onset and occurring 
 in predisposed individuals. Delirium tremens is altogether excep- 
 tional in typhoid fever. It is not so rare in smallpox and erysipelas, 
 but it is especially frequent in pneumonia. It expresses a profound 
 nervous perturbation, and occurs in alcoholic subjects as a result of 
 the toxomicrobic shock, as is sometimes produced by violent trau- 
 matism. 
 
 In diseases characterized by sudden invasion, a series of symptoms 
 which might be connected with visceral lesions, but which seem to 
 be dependent upon disturbance of innervation, is observed from the 
 very beginning. These are, vomiting without any apparent altera- 
 tion of the stomach ; diminution in the quantity of urine, at times 
 transitory suppression, without the kidneys as yet being affected; 
 intense dyspnea, unexplained by the condition of the lungs, and 
 acceleration of the pulse and arrythmia, which are in nowise de- 
 pendent upon cardiac lesions. There is a striking discord between 
 the functional and the anatomical conditions. 
 
 Thus far we have considered only those cases in which invasion 
 is announced by general phenomena. In other cases, infectious 
 diseases may begin with local manifestations, which at times precede, 
 sometimes accompany, the general reactions, and sometimes they 
 run their course without giving rise to any general phenomena. In 
 certain cases, however, the local lesions develop very rapidly. This 
 occurs in young subjects endowed with a nervous system which 
 reacts quickly and with energy, for example, in children attacked 
 by acute pulmonary congestion. The child is suddenly taken by 
 fever, and auscultation practised immediately reveals an intense 
 
EVOLUTION OF INFECTIOUS DISEASES. 
 
 blowing murmur. Everything is again normal on the following 
 day. The fever has subsided, and the murmur i no longer per- 
 ceptible. These fuels, which have been so well studied by Bergeron, 
 Cadet de (Jnssieourt, and llime, musl !«• considered a example 
 true abortive pneumonias. 
 
 Immediately upon its arrival the microbe gives rise to violenl 
 reactions which often resull in the instanl arrei I of n course. The 
 excitation of the nervous system is expressed by a congestive fluxion 
 which arrests the infection. In the same order of ideas, although 
 their meaning is more difficull to understand, we may mention 
 herpes, which is so frequently observed in infections, and urticaria, 
 which appears especially in cases of digestive disturbances. Evi- 
 dently the phenomena <>f fluxion are alone capable of making a 
 sudden appearance. The other responsive manifestations develop 
 more slowly, and if they at limes appear suddenly it Is bec;m~e 
 their beginning has been effected in a gradual manner and, having 
 already advanced to a certain degree, they suddenly give rise to 
 morbid reactions. There is often a lack of harmony between 
 general and local manifestations. In a certain number of cases 
 the two orders of symptoms begin simultaneously. In other.- the 
 disease is at first characterized by one or the other series of symp- 
 toms. In still other instances local reactions are progressive, while 
 general manifestations are abrupt, and vice versa. There exist, 
 therefore, a whole series of different modes of reaction of which 
 clinical experience furnishes well-known examples. 
 
 The same infection may sometimes start with local manifestations, 
 and at other times by general symptoms. Surgeons have empha- 
 sized this fact in describing phlegmons. They have remarked that 
 the beginning with general reactions indicates a greater virulence 
 of the morbid germ, and consequently a grave prognosis. This 
 remark is correct, but must not be generalized. In erysipelas, for 
 instance, these two modes of invasion occur without one being 
 more benign or more serious than the other. 
 
 The duration of the invasion period varies considerably according 
 to the infection under consideration, and is not absolutely fixed in 
 each disease. Authorities have endeavored, however, to establish 
 averages. It is generally admitted that invasion lasts two days 
 in scarlatina, three days in measles, and from two to five days in 
 variola. In the latter infection short invasions are observed, 
 especially in grave cases; long invasions in benign forms. In 
 
506 IXFECTIO US DISEASES. 
 
 erysipelas, invasion is supposed to last from a few hours to a day, 
 and the maximum is fixed at two days. 
 
 These rules are fairly exact, hut they suffer a certain number of 
 exceptions. According to our personal observations the classical 
 figure is observed in a little more than one-third of the cases of 
 measles in adults. In children below two years of age the period 
 of invasion is generally very short. In scarlatina invasion lasts 
 forty-eight hours in half of the cases ; it is not infrequently shorter, 
 but seldom longer. As to variola, the law of Sydenham, accepted 
 by Trousseau, is well known. An invasion of two days or two days 
 and a half indicates a confluent variola; an invasion of three days 
 and a half or four days and more particularly when it lasts five 
 days, indicates a discrete variola. Prof. Jaccoud has modified the 
 formula. He maintains that a short invasion may be followed by 
 a discrete variola, but a prolonged invasion never precedes a con- 
 fluent variola, Our statistics show that there are exceptions to 
 all these rules, and that variolas have at times been confluent after 
 periods of invasion lasting four, five, and even six days. Moreover, 
 we have inquired as to the applicability of Sydenham's law as 
 modified by Jaccoud to the majority of cases, and we have reached 
 the conclusion that in all forms of variola, excluding the primarily 
 confluent variety, invasion generally lasts three days. In one-third 
 of the cases it does not exceed one or two days. The law of Syden- 
 ham-Jaccoud is, therefore, exact in 54 per cent, of the cases. 
 
 Stationary Period. 
 
 Since the time of Hippocrates it has been customary to admit 
 three periods or stages in the evolution of acute diseases : an invading 
 period, a stationary period, and a period of decline. Jaumes has 
 proposed another division. He admits but two periods — i. e., one 
 characterized by a morbid effort corresponding to the period in 
 which the organism is overwhelmed, and one occurring only in 
 favorable cases, a period of improvement and restoration. In other 
 words, the first period corresponds to the attack of the pathogenic 
 cause, and the second to the curative effort of the organism. This 
 division is quite in harmony with the present-day conception of 
 disease. It would have been perfect if reaction really followed 
 action, and if disease followed a regularly descending course after 
 arriving at its height through a progressive aggravation. In reality 
 the facts are more complex. As we have repeatedly stated, the 
 
EVOLUTION OF INFECTIOUS DISEASES. 607 
 
 defensive reactions begin at the same time 8 the offensive action . 
 and at times even Ik -lore all appreciable ymptom . Consequently) 
 the two classes of symptoms con tantly intermingle, with the 
 exception, however, thai the pathogenic agenl has the advantage 
 in the beginning. The reactions of the invasion period indicate 
 that the organism is defeated, of a1 lea i on the defensive. Then 
 conies a period when ihe si niggle assumes a seriou character, and 
 the two participants fully display their forces. This i- the stationary 
 period, wliieh a1 limes seems io remain unchanged, and al others 
 a series of deviations occurs depending upon the various vicissitudes 
 of the struggle. This period is the mosl important from a noso- 
 logical standpoint, since the characteristic symptoms of the disease 
 are fully developed. They ;ire so grouped as to constitute a special 
 type which is easily defined and classified. It is a1 this moment 
 that a previously hesitating diagnosis may be made more certain. 
 
 In studying the stationary period the local symptoms and general 
 phenomena must likewise be taken into consideration. When the 
 local manifestations occupy the external pails they may readily 
 be studied. Such is the case with erysipelas, absce»e<. ;md phleg- 
 mons, cutaneous ulcerations and gangrenes. 
 
 These are also quite easily recognized when they occupy a mucous 
 membrane which is accessible to exploration, such as that of the 
 mouth and pharynx. In case a deeply seated organ is attacked, 
 the study becomes more difficult; yet, according to the modifications 
 manifested in the functions of the organ and the changes which 
 may be perceived by means of physical examination, palpation, 
 percussion, and auscultation, we can quite exactly determine and 
 follow the evolution of the phenomena produced in the deeper parts 
 of the economy. 
 
 In certain cases, even the minutest exploration fails to reveal 
 any organic alteration, because the symptoms are of a general 
 character. The latter consist in responsive manifestations referable 
 chiefly to the nervous system, the secretions, and thermogenesis. 
 The nervous symptoms are those which have already been noted 
 in treating of the invasion period — i. c headache, incapacity for 
 work, a diminution of psychical acuity, delirium, and. exceptionally, 
 convulsions. The secretions are for the most part diminished. 
 The urine is scanty, the saliva is not abundant, and the tongue is 
 dry. Finally, thermogenesis is also perverted, and there is usually 
 a rise of both peripheral and central temperature. 
 
508 INFECTIOUS DISEASES. 
 
 A comparison of local and general symptoms leads to the following 
 conclusions: Sometimes the local and general phenomena follow 
 a parallel course. They are aggravated or improved simultaneously. 
 They decline and disappear almost at the same time. Sometimes 
 there is a decided discord between the two orders of phenomena. 
 Thus, for instance, the local lesion may subside while the general 
 phenomena grow worse. In such cases there is generally some 
 fresh complication. More frequently the reverse is the case. The 
 general manifestations vanish, whereas the local symptoms seem 
 to remain stationary. This fact is particularly striking in pneu- 
 monia. From day to da}^ a sudden defervescence takes place. 
 The temperature, which had risen to 104° F. (40° C), falls to 98.5° F. 
 (37° C). The secretions are re-established; the patient experiences 
 a feeling of well-being which makes him realize that his sickness 
 is over, and yet no improvement has taken place in the condition 
 of the lung. On the contrary, the stethoscopic signs are the same 
 as the day before. The same lack of parallelism is observed in 
 erysipelas, but less constant^. The general phenomena subside, 
 while the cutaneous lesion persists without any change. Finally, 
 in certain cases the discord is no longer real, as in the preceding 
 examples, but only apparent. The local lesion seems to remain 
 unchanged, and yet the general phenomena are modified or even 
 aggravated. These indicate either a local change, which we are 
 thus enabled to recognize and predict, or a new perturbation, 
 perhaps a commencing complication. 
 
 In order to recognize the nature, follow the evolution, establish 
 the prognosis, and predict the possible accidents of a disease, we 
 must at the same time take into account the local and general 
 manifestations and their harmony or discordance. 
 
 Let us first consider the local phenomena. Five events are 
 possible • 
 
 1. The local lesion, which began during the period of invasion, 
 is not modified during the stationary period, but follows a very 
 simple evolution, increases gradually, reaches its height, and then, 
 in favorable cases, resolves. No notable change in its character 
 or aspect appears. Of numerous illustrations it will suffice to 
 mention mumps, erysipelas, and gonorrhea. We might add scarlet 
 fever and measles, in which the eruption characterizing the stationary 
 period extends progressively to all parts of the skin, but always 
 preserves an invariable aspect. 
 
EVOLUTION OF INFECTIOUS DISEASES. 609 
 
 2. In other cases the local lei ion i modified from day to day. 
 An abscess may be taken as an example in which exploration i- i 
 
 At first induration is present, then the lesion undergoe softening, 
 becomes fluctuating, and opens exteriorly. A like course may be 
 observed in ruses of visceropathies. In simple bronchitis there i 
 a period of crudity, when expectoration is difficult and painful. 
 Then a period of coction, when the sputa become mucopurulent 
 and arc easily expectorated. Examination of the sputa :i- well at 
 auscultation demonstrate the changes characterizing these two 
 periods. By the same methods of exploration we can follow per- 
 fectly the evolution of a pneumonic focus: In the beginning there 
 is pulmonary obstruction resulting from the exudations, and auscul- 
 tation reveals crepitant rales. Next, a fibrinous exudation into 
 the air cells takes place; this is the period of red hepatization, 
 characterized by tubular breathing. Lastly, the exudation softens 
 and auscultation reveals rales of resolution. 
 
 3. Instead of remaining localized in a region the local lesion ex- 
 tends and invades the neighboring parts. Here erysipelas and 
 pneumonia may again serve as examples. While often circum- 
 scribed, erysipelatous inflammation sometimes extends over a 
 great part of the skin. At times it covers the entire surface of the 
 body. This is a particular clinical form justly described under the 
 name ambulatory erysipelas. The same evolution maybe observed 
 in the lungs, under which circumstances pneumonia is designated 
 as migrating. In certain, but fortunately very rare, instance- a 
 local lesion grows both deeper and larger, causing considerable loss 
 of substance. This is known as phagedenism, and is observed 
 chiefly in the soft chancre, which lesion may destroy the penis, 
 invade the scrotum and thighs, and follow a serpiginous, extensive 
 course, the duration of which may be months or even years. 
 
 4. The local lesion sometimes progresses by successive st: s - 
 When the lesion seems on the point of subsiding, or has even disap- 
 peared, arecidive sometimes occurs in the region primarily attacked. 
 This is observed especially in erysipelas. In other instances the 
 recurrence takes place in parts more or less distant from the region 
 primarily diseased, for example, orchitis, occurring in mumps, and 
 endocarditis, pericarditis, or meningitis in pneumonia. The patho- 
 genic agent thus tends to colonize distant tissues or organs. The 
 process is, as it were, a relapse at a distance. In a certain number 
 of cases the appearance of a new morbid focus coincides with the 
 
510 INFECTIO US DISEASES. 
 
 disappearance of the primary focus. This is metastasis, the best 
 illustration of which is furnished by the history of rheumatism": 
 when cerebral manifestations appear the swelling in the articula- 
 tions subsides, the pain disappears, sometimes with astonishing- 
 rapidity: a transfer of the fluxion from the articulations to the 
 nervous centres occurs. 
 
 5. The local lesion may be modified by an additional infection. 
 Pathogenic microbes implanting themselves, for example, in a part 
 already diseased, give rise to suppuration, and may even invade 
 the economy. In gonorrhea the gonococcus often remains localized 
 in the urethra. Common bacteria, however, soon join it, and may 
 subsequently induce very serious disturbances. Although the gono- 
 coccus may at times invade the organism, the so-called gonorrheal 
 rheumatism generally depends upon ordinary pyogenic bacteria. 
 The process is one of attenuated purulent infection to which the 
 agent of gonorrhea has merely opened the way. 
 
 General phenomena usually follow a course parallel to that of 
 local symptoms. During the stationary period they may remain 
 quite unmodified. In pneumonia, for instance, the fever remains 
 about 104° F. (40° C). Dyspnea, thirst, and headache remain 
 about the same during the entire evolution. The same remark 
 holds true of typhoid fever, although some differences are revealed 
 by a more careful study. 
 
 In some instances the general symptoms are modified several 
 times, so that the stationary period has been divided into a certain 
 number of secondary periods. In other cases the general phenomena 
 keep pace with the local, as is observed in smallpox. Sometimes 
 the changes do not seem to harmonize. Thus, in tubercular menin- 
 gitis three periods, which apparently do not correspond to ana- 
 tomical changes, have been described according to the general 
 symptoms. After a phase characterized by violent headache, fever, 
 constipation, and vomiting, a marked remission occurs, which lasts 
 nearly a week. The patient is believed to be convalescent, when the 
 symptoms reappear and go from bad to worse, ending in death. 
 
 In a certain number of infections the modifications in the general 
 phenomena express the generalization of a primarily local microbic 
 process. Such is the case with malignant pustule. The lesion is at 
 first characterized simply by a cutaneous eschar. In certain cases 
 phenomena of general infection are subsequently produced, indicat- 
 ing the invasion of the economy by the pathogenic agent. Likewise, 
 
EVOLUTION OF INFECTIOUS DI8EA8ES. :,| | 
 
 in cases of septicemia or pyemia consecutive to local le ions, the 
 changes occurring in the general symptom reveal the invasion of 
 the organism. 
 
 Nosologists have divided the stationary period r >i di i 
 taking into accounl both the modifications occurring in the local 
 symptoms and the general manifestations. Undoubtedly these 
 divisions are not always perfect. Didactic description!: are tn 
 sarily schematic and cannot give an exacl idea of the complexity 
 of clinical phenomena. We have above referred to tubercular 
 meningitis. Its evolution in three phases, admitted by all classical 
 treatises, is, however, of rare occurrence. The phenomena very 
 seldom, if ever, progress with such quasi-mathematical precision as 
 has been attributed to them. The clinical types are, in reality, 
 far more complex and variable than may be supposed from classical 
 descriptions. 
 
 The general phenomena have been divided into continued, re- 
 mittent, intermittent, and irregular, mainly upon the basis of the 
 precise data of medical thermometry. After the details which we 
 have given in treating of the febrile process (p. 355), it will suffice to 
 say that general morbid manifestations run a course nearly parallel 
 to that of fever, increasing or diminishing with it, and thus present- 
 ing the same daily variations. There are, however, exceptions to 
 this rule. There may be dissociation between the two order.- of 
 phenomena. Febrile manifestations may diminish while the other 
 symptoms become aggravated. Such, for instance, is the case in 
 hepatic or renal lesions. We have then to deal with particular 
 clinical forms. 
 
 Clinical Forms. The stationary period of infectious diseases being 
 the longest and especially the best characterized, has served to 
 differentiate clinical types. On the basis of their evolution cyclic 
 diseases may be admitted in which the duration is sufficiently 
 defined and determined by a regular succession of morbid phenom- 
 ena. Pneumonia, typhoid fever, and eruptive fevers belong to 
 this category. It should be remembered, however, that the figures 
 given by authorities are subject to numerous variations. The term 
 of nine days assigned to pneumonia, and of three weeks To typhoid 
 fever, represent averages which are seldom realized. Nevertheless, 
 the term may be retained in contradistinction to non-cyclic dis« - s 
 such as diphtheria and erysipelas, whose capricious course defies all 
 efforts at averaging. Even in those diseases in which the stationary 
 
512 INFECTIOUS DISEASES. 
 
 period is best determined very great variations may be observed. 
 In certain cases the evolution is shortened, either because the disease 
 assumes a very acute, speedy course, causing death very rapidly, or, 
 on the contrary, because it follows an abortive course. Pneumonia 
 is again a good illustration. This infection may kill at times within 
 a few hours, as occurs in the aged, in diabetics, and in individuals 
 suffering from previous diseases, notably erysipelas. In this con- 
 nection we may also mention the speedy types of scarlatina, small- 
 pox, and cholera. Death may supervene at the beginning of the 
 stationary period, and even before the latter is clearly established. 
 
 Pneumonia likewise furnishes the best illustration of an abortive 
 infection. The disease begins suddenly, reaches the stationary 
 period, and all at once defervescence occurs on the third or fourth 
 day. Abortive typhoid fevers have also been described, and we may 
 likewise admit the occurrence of abortive eruptive fevers — i. e., 
 such as are cut short after a prodromic period. Thus, an individual 
 who has been exposed to the contagion of variola is seized with all 
 the premonitory symptoms of this disease; then the symptoms 
 disappear and the eruption is characterized by two small pustules. 
 This is evidently an instance of an attack of variola deserving the 
 name abortive. Notwithstanding the intensity of the symptoms of 
 invasion, the disease is cut short. Cases of abortive erysipelas, 
 which stop suddenly after the period of invasion, at the very begin- 
 ning of the stationary period, may also be admitted. It is useless to 
 multiply examples. While these facts are already well known, the 
 author believes them to be far more frequent than is usually supposed. 
 Many febrile paroxysms, transitory indispositions, and sudden chills, 
 which are followed by no special manifestations whatever and which 
 run their course in a day and sometimes in a few hours, are to be 
 accounted for by an infection that is abortive. Consecutive to 
 infections occurring during convalescence from eruptive fevers or 
 erysipelas, we often see febrile paroxysms which, apparently, are 
 referable to no other cause. This is demonstrated by the fact that 
 numerous transitions are observed between the ephemeral fevers, 
 which can in nowise be accounted for, and those which indicate 
 relapse or a complication. 
 
 By the side of diseases aborting spontaneously should be placed 
 those aborting in consequence of therapeutic intervention. Cases 
 of this kind, formerly rare, will become more and more frequent as 
 we become better acquainted with specific medication. The latter 
 
EVOLUTION OF INFECTIOUS DISEASES. :,|:; 
 
 is sometimes represented by vegetable or mineral producl . Such 
 are the salts of quinine, whirl: arrest malarial infection, and the 
 salts of silver, which stop ;i beginning gonorrhea, and especially the 
 preparations of mercury, which suspend the evolution ol syphilis. 
 At present specific and abortive remedies are looked for in Bub- 
 stances derived from immunized animal . The results obtained by 
 serum therapy inspire us wild the hope thai the time is nol far 
 distant when it will be possible i" arresl the evolution of a ■. 
 number of infectious diseases. 
 
 The acute infections, even when they generally follow ;i cyclic 
 course and terminate within a well determined time, may in some 
 cases be prolonged beyond the usual limits. For instance, pneu- 
 monia, instead of lasting nine days, may not reach defervescence 
 until toward the twelfth or even the fifteenth day. Likewise, 
 typhoid and eruptive fevers are nol infrequently prolonged in an 
 unusual manner, although examination of the patienl fails to explain 
 the persistence of the morbid symptoms. There is, bo to say, a 
 torpidity of the organism which fails to produce the special con- 
 ditions capable of arresting the infection. 
 
 In a great number of cases, however, prolongation of the cha 
 is clue to a particular course or to the influence of complications. 
 The evolution is prolonged as the result of successive invcu 
 At the moment when the infection is believed To have nearly termi- 
 nated a new focus is produced. Pneumonia and typhoid fever may 
 evolve in this manner, and, although the new attack is generally of 
 shorter duration than the first, the total duration is thereby con- 
 siderably prolonged. This mode of evolution, while rare in the 
 diseases above referred to. is the rule in certain infections. Such 
 is the case with recurrent typhus, intermittent fever, and varicella, 
 the duration of the last-named disease being extremely variable on 
 account of the variation presented by the course of successive 
 recurrences. In certain cases the recidive of morbid symptoms is 
 preceded by a certain interval of recovery. A recurrence is then 
 said to have taken place. As in the case of relapse, recurrence is 
 generally less grave than the first attack: but this rule is subject 
 to a great number of exceptions. 
 
 Finally, morbid evolution may he prolonged by reason of com- 
 plications occurring during the stationary period or convalescence. 
 New phenomena, mostly referable to superadded infections .[may thus 
 lengthen the duration of a disease for a considerable period of time. 
 
 33 
 
514 ISFECTIO US DISEASES. 
 
 It is evident that nothing; but hypotheses can be advanced as to 
 the causes which intervene to abridge or prolong infections. Aside 
 from those cases in which secondary complications are responsible, 
 it is not understood why morbid action is cut short and then re- 
 appears when defervescence is about to set in or even after con- 
 valescence has began. The solution of these problems is intimately 
 connected with the study of predisposition, immunity, and the 
 mechanism of recovery. If, as is generally admitted, recovery is 
 effected by virtue of chemical and dynamic modifications pro- 
 duced within the organism ; if it is dependent upon an increase of 
 the germicidal power of the tissue fluids and upon the phagocytic 
 activity of the cells, the duration of the disease will, of course, 
 depend upon the rapidity of the organic changes, namely, upon the 
 responsive potency of the economy. Relapses, on the other hand, 
 would be due to an insufficiency of reaction. This explanation, 
 however, is inadequate. What we desire to determine are the causes 
 or conditions which arouse the responsive activity of the economy 
 promptly in one case, slowly in another, and incompletely in a 
 third. The question is thus reduced to a problem of a much more 
 general nature. In a very great number of conditions morbid re- 
 actions are observed which are partly dependent upon the nervous 
 system and partly upon the state of general nutrition. These 
 reactions vary considerably from one subject to another, and this 
 variability is connected with the hereditary or personal ante- 
 cedents, special innate characteristics, and idiosyncrasies of the 
 individual ; in brief, with the various causes to which we have con- 
 stantly referred to explain the development and course of diseases. 
 
 Differences in reaction likewise explain differences in termination. 
 When reaction is energetic and timely it succeeds in destroying the 
 invading microbes. If slight and slow it only arrests their progress, 
 and the process passes into a chronic condition. If too weak or 
 too tardy it fails to save the organism, and the disease terminates 
 in death. 
 
 These considerations suffice to demonstrate that the same in- 
 fectious disease may present varied symptoms and follow an ex- 
 tremely variable evolution. Supposing all conditions to be the 
 same as far as the microbe is concerned, the influence of the organism 
 makes itself constantly felt and contributes to modify the scene- 
 Therefore, a certain number of clinical forms have been admitted. 
 These divisions are evidently arbitrary. In order to establish them, 
 
EVOLUTION OF INFEOTIOUB DI8EA8ES. :,\'> 
 
 the various cases encountered have been compared with an habitual 
 average type, running its course without the intervention of any 
 unusual influence. In this way clinical form have been grouped 
 under two heads: First, according a modifications depend upon 
 some anomaly in the course, morbid symptoms, or localization. 
 Second, according as they are due to the condition of the subject. 
 Willi some variation this division may be applied to ;ill infections. 
 
 In order to fix the ideas, lei us consider the two disea e in which 
 clinical types are the mosl numerous and the mosl varied, namely, 
 pneumonia and typhoid fever. 
 
 The following two tables will show how clinical forms may be 
 classified. The terms sanctioned by usage are sufficiently clem- to 
 make description unnecessary: 
 
 CLINIC \l, li )I!MS < >l PNE1 m IN] \ 
 
 I. Divisions Based on the Study of the Disease. 
 
 1. According to the course. 
 Abortive pneumonia. 
 Speedily fatal pneumonia. 
 Prolonged pneumonia. 
 
 Double. 
 
 With successive foci. 
 Migrating. 
 Infecting pneumonia. 
 
 2. According to the morbid elements or symptoms. 
 1 nflammatory pneumonia. 
 
 Adynamic pneumonia. 
 Ataxic pneumonia. 
 Pneumonia with icterus. 
 Bilious pneumonia. 
 
 3. According to localization. 
 Pneumonia of the base. 
 Pneumonia of the apex. 
 Central pneumonia. 
 Massive pneumonia. 
 Pleuropneumonia . 
 
 II. Division Based on the Condition of the Subject. 
 
 1. According to age. 
 Pneumonia of children. 
 Pneumonia of the aged. 
 
 2. According to the previous state of health. 
 Pneumonia of cachectics. 
 Pneumonia of drinkers. 
 
 Pneumonia of the obese. 
 
 Pneumonia of diabetics. 
 
 Pneumonia of bronchiti.CS. 
 
 Pneumonia of the tubercular. 
 
 Pneumonia of those suffering with~malaria.'etc. 
 
516 INFECT 10 US DISEA SES. 
 
 3. According to the coexistence of another injection. 
 Pneumonia of typhoid fever. 
 Pneumonia of erysipelas. 
 
 Pneumonia of acute articular rheumatism, etc. 
 Pneumonia of influenza. 
 
 CLINICAL FORMS OF TYPHOID FEVER. 
 
 I. Divisions Based on the Study of the Disease. 
 
 1. According to the course. 
 Abortive typhoid fever. 
 Prolonged typhoid fever. 
 Speedily fatal typhoid fever. 
 Typhoid fever with relapses. 
 
 2. According to the morbid elements. 
 Mucous typhoid fever. 
 Ambulatory typhoid fever. 
 Inflammatory typhoid fever. 
 Bilious typhoid fever. 
 Hemorrhagic typhoid fever. 
 Ataxic typhoid fever. 
 Adynamic typhoid fever. 
 Putrid typhoid fever. 
 Hyperpyretic typhoid fever. 
 Sudoral typhoid fever. 
 
 3. According to the localizations. 
 Nervous forms. 
 
 Meningeal. 
 
 Spinal. 
 Thoracic form. 
 Gastric form. 
 Icteric form. 
 Renal form. 
 Cardiac form. 
 Septicemic form. 
 
 II. Divisions Based upon the Condition of the Subject. 
 
 1. According to the age. 
 
 Typhoid fever of children. 
 Typhoid fever of the aged. 
 
 2. According to the previous condition of health. 
 
 Typhoid fever of cachectics. 
 Typhoid fever of the obese. 
 Typhoid fever of drinkers. 
 Typhoid fever of the tubercular. 
 
 3. According to the coexistence of another infection. 
 
 Typhoid malaria. 
 
 Laryngotyphus. 
 
 Pneumotyphus. 
 
 Termination of Infectious Diseases. 
 
 We have repeatedly shown that the organism is provided with 
 means of protection which prevent penetration and multiplication 
 
EVOLUTION OF INFECTIOUS DISEASES. :,I7 
 
 of pathogenic germs. The latter may succeed in invading the 
 economy only when the vigilance of the cells is diverted for a moment 
 and the fluids are altered by some affection. The di ea e then 
 manifests itself. Modifications in cellular nutrition are immediately 
 produced, however, which transform the blood, the fluids, and the 
 tissues, and make of them unfavorable culture media for the patho- 
 genic agent. Two events are then possible: I. In Borne case* the 
 changes are produced slowly and progre ively; the organism gradu- 
 ally rids itself of the germs and neutralizes the action of the toxins 
 which impregnate it. Defervescence is -lowly effected; the fever u 
 progressively reduced by lysis, and the various functions consume 
 a more or less long period of time in returning to their normal con- 
 dition. M is, therefore, possible to follow the progress of recovery 
 day after day. This is what takes place in typhoid fever. '2. In 
 other instances, on the contrary, the termination is abrupl and 
 sudden as in pneumonia. It is then said that a crisi has occurred. 
 
 Crises. From the earliest antiquity it has been noted thai certain 
 diseases may present sudden changes in their evolution. This is 
 crisis, which supervenes when the corrupl humor (humeur peccant) 
 has undergone coction. Nature expels it from the body or causes 
 its deposition in some part of the economy. The latter result was 
 formerly considered fortunate or unfortunate according as deposition 
 occurred in an organ of little importance or indispensable to life: 
 These ideas led Hippocrates to formulate the following definition: 
 "A crisis in diseases is either an exacerbation, decline, a metaptosris, 
 another affection, or the end." 
 
 The crisis, however, did not occur at undetermined periods. It 
 was produced on fixed days, called criticcd days, which corresponded 
 to weeks or half weeks — that is to say. to the fourth, seventh, tenth, 
 fourteenth, seventeenth, and twentieth days. The critical days 
 were preceded by the indicating days, when an exacerbation of the 
 symptoms was usually observed. We must add that Hippocrates 
 did not regard the critical days as possessing an absolute value. The 
 crisis might occur twenty-four hours sooner or later. Galen, on 
 the other hand, attributed to each day an absolute significance. 
 He contended that acute diseases did not last more than forty days, 
 and considered the crisis as a sudden reversion to health. 
 
 The latter definition has prevailed. At the present day the name 
 crisis is reserved for cases in which the change is favorable. In 
 infectious diseases this change is characterised by the following 
 
518 INFECTIOUS DISEASES. 
 
 phenomena: A sudden fall in temperature, a rapid increase of the 
 urine, the re-establishment of secretions, and the elimination of 
 noxious substances accumulated during; the disease. According to 
 prevailing ideas or the conceptions of the observer, attempts have 
 been made to' define crisis by thermal defervescence or by urinary 
 modifications. In recent years, attention having- been drawn espe- 
 cially to the modifications of cellular activity, Dr. Chauffard has 
 proposed the following definition: An intimate and sudden act 
 which terminates the morbid evolution and at the same time gives 
 rise to an ensemble of nutritive and functional mutations. 
 
 As we are dealing only with infections, we may look for the char- 
 acteristic nature of the crisis in the most striking clinical phenomena 
 which occur at this moment of evolution. The symptomatic modi- 
 fication is so marked as to have sufficed to reveal the existence of 
 crises before the introduction of the modern methods of investiga- 
 tion, such as thermometry, urology, and the investigations on 
 nutrition. 
 
 An individual who was deeply infected on the previous evening 
 is found completely cured on the following morning. This is the 
 clinical characteristic of the crisis. Setting aside all theoretical 
 discussions, we may adopt the following definition : ' ' Crisis is char- 
 acterized by the sudden disappearance of morbid manifestations." 
 We do not say morbid phenomena, since the local lesion persists ; it 
 is the general reactions that subside. As we have repeatedly stated, 
 these reactions are dependent upon intoxication. Consequently 
 cessation of the disturbances indicates that the poisons have been 
 abruptly eliminated or neutralized. The study which we are about 
 to undertake will show that the latter hypothesis is the more prob- 
 able. On the ground of the results acquired by the study of arti- 
 ficial immunity it may be admitted that neutralization of the poisons 
 depends upon a modification in the cellular nutrition which protects 
 the anatomical elements against the toxic influence. If this is true 
 we ma3^ place by the side of the symptomatic definition above 
 proposed a definition drawn from the very essence of crisis — i. e., 
 from the study of pathological physiology. Therefore we may say: 
 " Crisis is essentially characterized by a sudden neutralization of 
 microbic toxins, namely, by an immunity conferred upon the cells 
 against their action." To those who may wonder why this terminal 
 modification is produced or rather manifested in a sudden manner 
 we shall answer that the situation is precisely the same at the period 
 
EVOLUTION OF XNFE0TI0U8 DI8EA8E8. 519 
 
 of invasion. For instance, pneumonia begin and terminates with 
 the same instantaneousness. 
 
 Supersaturation of the organism by the toxin wa nccfMaty in 
 order for a reaction to be produced and for the disease to be estab- 
 lished. Likewise, supersaturation of the organi m by antitoxin* i- 
 necessary in order for the disturbances of toxic origin to be neutral- 
 ized. 
 
 There is an interesting fad thai bad nol escaped the attention of 
 ancient observers, namely, thai crisis is oft en preceded by the so-called 
 precritical phenomena, consisting in, an a1 times, alarming aggrava- 
 tion of the symptoms. The temperature rises to a higher figure 
 than on the preceding days. The pulse is weaker and more rapid. 
 Dyspnea is very intense, and sometimes the body is covered with 
 cold perspiration. The subjective sensations experienced l>y the 
 patient are in harmony with these objective disturbances, and 
 hence increase the anxiety of those about him. The contrasl i- 
 still more striking when the individual seems to be cured the n<\\t 
 morning. 
 
 In other cases the crisis is preceded by a procrisis. The temper- 
 ature is suddenly reduced, and may even fall to the normal. The 
 other symptoms subside, and one migb! believe the evolution at an 
 end. In the evening, however, the disturbances are renewed, to be 
 terminated in a definite manner on the following day. In still other 
 cases a false crisis occurs. During twenty-four or forty-eight hours 
 a relative subsidence takes place, and the temperature is lower than 
 on the preceding days. Then the morbid symptoms are again 
 renewed to disappear suddenly and definitively a few days later. 
 
 In most cases the crisis is produced during the night. It is. 
 therefore, surprising to see the patient who was very sick the previous 
 evening completely cured in the morning. The general phenomena 
 have disappeared. The patient realizes this by the feeling of well- 
 being which, doubtless, constitutes one of the most astonishing 
 manifestations. He has the feeling that the disease is at an end and 
 that he has entered upon convalescence. The tongue, which was 
 dry, becomes moist. The skin, which was dry or covered with cold 
 perspiration, recovers its agreeable moisture. The pulse, which was 
 weak and rapid, becomes strong and slow. The change which i> at 
 present most easily observed is the sudden fall of temperature. The 
 patient who on the previous day had 104° or 105.S° F. (40° or 41° C. 
 has no more than 98.6° F. (37° C). This reduction of several 
 
520 INFECTIOUS DISEASES. 
 
 degrees is produced within twelve hours. In some cases, however, 
 it is effected more slowly — in thirty-six hours. At times the ther- 
 mometer shows a fall to a subnormal degree, not exceeding 96.8° F. 
 (36° C), and the temperature may remain at this point for several 
 days. 
 
 The sudden and profound change produced at the moment of 
 crisis may give rise to new nervous reactions which constitute the 
 so-called epicrisis. In children this is manifested by convulsions; 
 in the aged by collapse, which is sometimes so marked as to make 
 it a difficult matter to warm the patient. In adults, delirium and 
 in some instances delirium tremens occur. I have observed several 
 cases in which patients, who had manifested not the slightest intel- 
 lectual disorder during the stationary period, develop delirium, 
 sometimes of an intense character, at the moment of recovery, 
 strangely contrasting with the amelioration or disappearance of the 
 other s}^mptoms. The intellectual disturbance, however, is rapidly 
 cured, and does not indicate an unfavorable prognosis. Its patho- 
 genesis is the same as that of the initial delirium. The change 
 suddenly occurring in the economy has disturbed the equilibrium 
 or the quietude of the predisposed nervous system, thus provoking- 
 violent reactions. 
 
 Special attention must be devoted to changes presented by the 
 blood and the secretions. Dr. Hayem has described a hemic crisis, 
 in which the white corpuscles, increased in number during the 
 disease, resume their normal number. The red corpuscles progres- 
 sively diminish, and at the time of the crisis an activity on the part 
 of the hematoblasts occurs, designed to increase the red globules. 
 We have already referred to the moisture of the skin. At times 
 this cutaneous manifestation is more intense. Sweating is profuse, 
 and serves probably for elimination of the toxins. There may also 
 be observed other manifestations, such as erythemata, outbreaks 
 of urticaria and herpes, sometimes diarrhea, a bilious attack, or 
 epistaxis. 
 
 During the disease the quantity of urine progressively diminishes. 
 At the moment of the crisis a discharge occurs. The polyuria is very 
 abundant. Voiding of two and three litres is not rare. The urine is 
 less highly colored than during the stationary period. At this time 
 it corresponds to the numbers 4 and 5 of the scale of Neubauer and 
 Vogel. At the time of defervescence it corresponds to the numbers 
 2 and 3. Not infrequently the density is increased. In one instance 
 
EVOLUTION OF INFECTIOUS DI8EA8E8. 521 
 
 I found it to be from L. 025 to L.031. The reaction i often neutral 
 and sometimes alkaline. The soluble ubstance undergo till more 
 interesting variations. The urea, which may have been reduced to 
 12 or L5 grams during the stationary period, ri e to 30 or K) grams. 
 The chlorides, which were represented by I or even 0.8 gram, reach 
 10 and 12 grams. The modifications in the amount of chlorides 
 have been attributed fco the diet. Thu opinion i inadmif ible, for 
 it is contradicted by the abundant discharge at the momenl of 
 recovery. II. is also known thai if chlorides or iodide* are admin- 
 istered fco pneumonia patients, these substances accumulate in the 
 organism and are eliminated only at the time of crisis. Lifa 
 the phosphates and the sulphates increase when defervescence \& 
 established, although in less notable proportions. 
 
 The same is true with regard to those poisons which are normally 
 excreted by the urine, they being in g^eal pari retained in the 
 organism during the disease. During the stationary period the 
 toxicity of the urine progressively diminishes. At the time of crisis 
 it is considerably increased and reaches or even exceeds the normal 
 figure. It should not, however, be concluded from this resull that 
 recovery is due to the sudden elimination or to the urotoxic discharge. 
 On the contrary, the reverse is true. Crisis appears because tin- 
 patient has recovered. This is proved by the fact that in certain 
 cases the urinary crisis occurs twenty-four hours before, or, what i- 
 more demonstrative, after recovery. Thus, the patient being cured. 
 he is capable of rejecting the poisons which impregnate his organism, 
 but to which he had already become insensible. 
 
 Crisis in Pneumonia. The disease in which crisis i- best char- 
 acterized is incontestably lobar pneumonia. In typical forms the 
 temperature falls to the normal within a night. 
 
 Pneumonia does not always terminate in this manner, however. 
 This infection is, perhaps, the one in which the symptoms and 
 evolution are most modified within the last years. Thus, we quite 
 often see the termination effected in a slow and progressive manner. 
 The fever is reduced little by little, then it persists for day- and even 
 weeks. Under such conditions diagnosis becomes difficult and 
 wavers between a pneumonia with a slow course and a pulmonary 
 tuberculosis. Even in such cases, however, certain critical manifes- 
 tations are found, especially some interesting modifications in the 
 characters of the urine. 
 
 Let us first consider the observations in which the crisis is quite 
 
522 INFECTIOUS DISEASES. 
 
 clear. In such cases the quantity of the urine is increased, but 
 this phenomenon does not always coincide with defervescence. It 
 may begin a day or two earlier or, on the contrary, appear only 
 at a later period. At times the polyuria is not established until 
 the moment pf convalescence. The amount of urea is sometimes 
 increased, at other times diminished, while the chlorides are always 
 increased. Furthermore, we have pursued, with Dr. Gaume, some 
 researches on the variations of the urinary toxicity, studying from 
 the standpoint of the urinary syndrome eleven patients suffering 
 from pneumonia. In seven of the cases the termination was effected 
 by sudden defervescence. In two others the fever terminated 
 slowly after having presented numerous variations. In the last two 
 cases the disease ended fatally. 1 
 
 In the first seven cases polyuria was present only twice. The 
 increase of the urea, however, was very marked. From 13 grams, 
 which was the figure obtained during the stationary period, the 
 amount of urea rose suddenly to 35 and 40 grams and even 50 grams. 
 This excess was observed on the day of the crisis and the day follow- 
 ing. The modifications in the chlorides were still more striking. 
 During the stationary period we found 0.8 to 2 grams. On the day 
 following defervescence the figure rose to 10 and 12 grams. During 
 the disease there was a notable diminution in the urinary toxicity, 
 it being two or three times less than under normal conditions. 
 This result may be partly attributed to the fact that the patient 
 was confined to a milk diet; but this condition is not sufficient, for 
 it cannot explain the increase of toxicity at the moment of the 
 crisis, when the diet was exactly the same as before. I believe, 
 therefore, that the various urinary poisons, like the chlorides, are 
 retained in the organism and are eliminated at the moment of the 
 defervescence. A urotoxic discharge is thus produced, lasting for 
 a day or two. 
 
 Thus, urinary toxicity is very low during the febrile period of 
 pneumonia, and it often diminishes as the disease advances; then 
 a urotoxic discharge suddenly supervenes, lasting from twenty-four 
 to forty -eight hours, and reaching its maximum on the day of thermal 
 crisis, exceptionally on the following day. After the crisis this 
 toxicity slowly diminishes in some cases, rapidly in others, and may 
 again fall to extremely low figures during convalescence. 
 
 1 Roger and Gaume. Toxicity de Purine dans la pneumonie. Revue de midecine, 
 April 10, 1889. 
 
/<; v<> L UTIO v OF I NFEOTIO US i> I8EA 8E8. 
 
 In two of our cases the fever, instead of terminating in a sudden 
 manner, was reduced slowly. In one of them the urotoxic crisi 
 was produced at the tnomenl when the temperature had begun to 
 decline, and lasted two days, presenting the usual character , in 
 the oilier case an incomplete crisis wb fir I observed, coinciding 
 with a urotoxic crisis. Subsequently the fever recurred and the 
 urinary toxicity ;ig;iin diminished. A new urotoxic dischargi 
 little less pronounced than the first, occurred three daye later. 
 From this momenl on the course of the disease tended rapidly 
 toward recovery. 
 
 Finally, in two of the cases the disease terminated in death, but 
 the evolution was in several respects comparable to the preceding 
 two cases. The course was prolonged. There was do defervescence, 
 but several febrile subsidences occurred, coinciding with urotoxic 
 discharges. 
 
 All these facts concur to demonstrate the existence of a urotoxic 
 crisis, even in fatal cases, although in the latter the discharge of the 
 poisons is not well marked. 
 
 It would evidently be very interesting to further study these 
 phenomena and to determine the substances to which the toxicity 
 of the urine is due. Feltz and Ehrmann attribute it to potassium 
 salts, but the analyses which we have made have not enabled us to 
 find any clear relation between the variation of the salts and the 
 changes of the toxicity. Authorities are at present inclined to 
 believe that a toxic role is played by ptomains, produced, perhaps, 
 by the microbe of pneumonia. Drs. Lepine and Guerin have found 
 alkaloids in pneumonic urines. By examining 200 cubic centi- 
 metres of urine, they found ptomains which when injected into 
 frogs killed them within twenty-four or forty-eight hours. In 
 grave cases they found much more toxic alkaloids. Thus, in one 
 observation the alkaloids of 250 cubic centimetres of urine sufficed 
 to kill a frog in two hours. The most interesting fact, however, is 
 that the day following defervescence they could obtain hardly any 
 toxic bases, even by employing 900 cubic centimetres of urine. 
 Whatever the active substances may be. the urine oi pneumonia 
 patients differs from normal urine in that it is highly convulsant 
 and often causes salivation. Normal urine also contains a sial 2 
 substance, but the action of the latter is masked by the other pois 
 It must be extracted from the urine, while its presence is manifest 
 in pneumonic urine even when the total urine is injected. 
 
524 IXFECTIO US D1SEA SES. 
 
 Crisis in Typhus. Next to pneumonia, typhus fever is, perhaps 
 the disease which most clearly terminates by crisis. Its fever chart 
 recalls fairly well that of pneumonia. The rise is sudden, and on 
 the evening of the first day the temperature reaches 102.2° F- 
 (39° C). During the stationary period the fever oscillates between 
 102.2° and 105.8° F. (39° and 41° C). Defervescence is often pre- 
 ceded by a precritical period during which the temperature is slightly 
 reduced. At the moment of crisis, which is effected in twenty-four 
 or forty-eight hours, it often falls below normal. Coinciding with 
 the fall of the temperature there is a complete and truly astonishing 
 modification in the general condition of the patient — stupor dis- 
 appears, the skin becomes moist, and the sleep sound. Finally, the 
 urine, which was scanty and red, becomes profuse and pale. 
 
 Crisis in Erysipelas. Erysipelas is often cited among diseases 
 which terminate by crisis. In fact, there are cases in which defer- 
 vescence occurs in an abrupt manner as in pneumonia, Between 
 evening and morning the temperature falls from 104° to 98.6° F. 
 (from 40° to 37° C), not to rise again. Oftener, however, defer- 
 vescence takes forty-eight hours, either because the temperature is 
 reduced gradually, or because, after a fall to 98.6° F. (37° C), it 
 once more rises on the evening of the first day, and does not remain 
 normal until after the second day. Finally, the temperature is not 
 infrequently reduced by lysis, presenting a series of variations. 
 Whatever the mode of termination may be, a hypothermic state in 
 which the temperature falls to 96.8° F. (36° C), sometimes even 
 to 96.4° F. (35° C), often occurs after defervescence. In two cases 
 we have found 94.7° F. (34.8° C.) in the absence of any notable 
 disturbance. 
 
 The study of thermal modifications should be supplemented by 
 investigation of the urinary variations. The researches which we 
 have pursued on this subject, with the assistance of Dr. Marsat, 1 
 demonstrated that the modifications are analogous to those observed 
 in pneumonia, except that they are less pronounced. During the 
 stationary period the urine is scanty. The amount does not exceed 
 700 or 900 cubic centimetres, the color being mahogany red. The 
 density rises and varies between 1.022 and 1.030. The reaction is 
 acid. At the moment of convalescence a critical polyuria is pro- 
 duced. The amount voided rises to 1500 and 2000 cubic centi- 
 
 1 Marsat, Essai d'urologie olinique dans l'6rysipelc. Thfese de Paris, 1S94. 
 
EVOLUTION OF INFECTIOUS DISEASES. 525 
 
 metres. The color is clearer, and the density fEll bo L.017and L.010. 
 At this time a transitory incontinence of urine which la I a da 
 two occasionally occurs in women. The modification in the urea, 
 phosphates, and chlorides are far less marked and clear than in 
 pneumonia. The chlorides diminish, as in pneumonia. ( 'i the • 
 from 2 to o' grams are, however, found during the Btal ionary period. 
 At the moment of convalescence the daily figure rises to I- and 13 
 grams. The modifications in the phosphates are very irregular. 
 In the majority of cases (here is diminution during thi tationary 
 period and n return i,o (he normal al the time of convalescence ; but 
 the modifications in the phosphates are often produced iii a -udden 
 and unexpected way which is not explained. 
 
 Crisis in Scarlatina. Among the eruptive fevers scarlatina de- 
 serves particular attention. The researches pursued in our labor- 
 atory by Dr. Mazaud 1 showed with accuracy the urotoxic variations 
 produced in this infection. At the beginning of scarlatina the urine 
 is scanty. The absolute toxicity is high — i. <■. a small amount 
 when injected into animals suffices to cause death. If, however, 
 the volume is taken into account, it is found that the individual 
 eliminates in the twenty-four hours less poison than under normal 
 conditions. When the urine is albuminous it often presents peculiar 
 properties. It gives rise to intestinal movements which are more 
 or less violent and followed by diarrhea. These manifestations are 
 absent when the urine contains no albumin. It is, therefore, prob- 
 able that the albumins of the stationary period, which are mainly 
 constituted by globulins, possess toxic properties. Whether albu- 
 minous or not, the urine at the beginning of the disease is always 
 convulsant. Hence it seems to contain nerve poisons, a fact which 
 is in perfect harmony with the symptoms presented by the patients. 
 
 At the moment of recovery a urinary crisis occurs, supervening 
 in most cases on the tenth or eleventh day. The urinary and the 
 urotoxic crisis are effected at about the same time, but the coinci- 
 dence is not absolute. An interesting fact is that the temperature 
 is always reduced before the urotoxic crisis appears. In scarlatina 
 as well as in pneumonia recovery precedes and explains the crisis. 
 
 Crises in Various Infections. Among the other infections Termin- 
 ating by crisis, although less marked and clear than in the preceding 
 examples, variola, varioloid, and mumps may be cited, as well as 
 
 1 Mazaud. Recherches experiment ales sur les variations de la texicite des urines au 
 cours de la scarletine. These de Paris. 1S98. 
 
526 INFECTIOUS DISEASES. 
 
 typhoid fever, which in one-fourth of the cases, according to Prof. 
 Jaccoud, instead of terminating slowly, as is the rule, ends abruptly. 
 We may likewise mention malaria, the crises of which have been 
 well studied by Mosse", Roques, and Lemoine; and recurrent fever, 
 the spirilla of which appears in the blood before the paroxysm and 
 disappear a little before the crisis. Infectious icterus must not be 
 overlooked. Chauffard has thoroughly studied the characters of the 
 urinary crisis in catarrhal icterus. Since the works of Bouchard 
 and of Mosse it is known that primary grave icterus often terminates 
 in recovery and that disappearance of the symptoms coincides with 
 a urinary crisis running a course parallel to the increase in the urine 
 and urea. Another element may at present be added — i. e., urinary 
 toxicity. 
 
 Cholera. There is a disease in which crisis occurs in a reverse 
 direction: that is cholera. In the stationary period the temperature 
 is below normal. At the moment of recovery it rises above and 
 sometimes reaches a figure notably above the normal. Thus a 
 febrile, reactionary period develops, sometimes attended by grave 
 manifestations which may impart to the patient a typhoid aspect. 
 
 Conclusions. The facts above reported suffice to demonstrate 
 that crisis is the result and not the cause of recovery. It must be 
 considered simply as a process resulting from an exaggeration of 
 normal phenomena. It is established that in a healthy man the 
 elimination of autogenous poisons is not effected in a continuous 
 manner. The urinary secretion varies from one day to another. 
 It follows a tertian and less frequentty a quartan type. Then, even 
 in a normal state of things, accumulations and discharges are con- 
 stantly produced — that is to say, little crises. This is a particular 
 example of a general law. We have already shown that there is 
 no uniform movement in nature, and that all vital acts are remittent. 
 Starting from this physiological fact, we may regard crisis as a 
 natural phenomenon or an exaggeration of the normal type. 
 
 On the other hand, it seems to us that the termination of the 
 disease must be attributed to a change occurring in the activity of 
 the infectious agent. Netter and Patella have shown that at the 
 moment of crisis the pneumococci succumb or are attenuated. It 
 is probable that, under the influence of antitoxins, the microbe 
 ceases to elaborate toxins. At the same time the cellular reaction 
 which has terminated in the production of antitoxins must have 
 armed the nervous centres against the effects of impregnation. 
 
EVOLUTION OF INFECTIOUS DISEASES, 527 
 
 When this reactionary process is a1 an end the nervoi 
 become indifferenl to the toxins which 'ill remain in the economy, 
 and which, as experience demon are nol eliminated until 
 
 twenty-four hours later. Hence we conclude thai the prin 
 phenomenon is a chemical tram formation occurring in the organism 
 protecting the cells againsl the toxins; in other word . rendering 
 the cells capable of enduring the microbic poison as if the organism 
 were vaccinate) I. Under these conditions the toxic action i 
 longer exercised. The symptoms disappear, cellular activil 
 re-established, and elimination of the poisons may I"- effected. This 
 is the last act of the critical evolution. 
 
 Convalescence. When the morbid process 3eems to have been 
 arrested and recovery established, the organism fc qoI yel com- 
 pletely restored to its normal condition. There is -till a lasl period, 
 termed convalescence. 
 
 The appetite, which had been suppressed during the diw 
 reappears, and ii is often so marked thai it is difficull to prevenl th<- 
 patient from overeating. The temperature often falls below normal. 
 The figures 07.7° and 96.8° F. (36.5° and 36° C.) are nol infrequent, 
 and may be observed for a week or more. Emaciation appears or 
 increases, this probably being due to the greal amounl of \ 
 which is eliminated by the different emunctories, notably through 
 the respiratory apparatus and the kidney.-. Then, at the end of a 
 few days, the patient grows fat, his weight often exceeding that 
 noted before the commencement of the disease, and at times he 
 becomes slightly obese. The nervous system having been most 
 affected during the stationary period, therefore returns more slowly 
 to its normal condition. During the first days following recovery, 
 when all the organs are working regularly, the nerv< m is 
 
 still disturbed. The individual is unable to keep on his feet or walk. 
 If an abrupt movement is attempted, dizziness and palpitation are 
 experienced. Now and then a febrile paroxysm occurs, as, for 
 instance, when he happens to read a little too much, or on the 
 occasion of a visit, an emotion, or an exertion of little importance, 
 such as making his toilet. The thermometer then marks LOO. 
 101.3° F. (38° or 38.5° C). These disturbances, which seem to 
 depend simply upon a lack oi equilibrium in the centres of thermal 
 regulation, and not upon an additional infection, are transitory anil 
 in no wise disquieting. The nervous manifestations of convales- 
 cence, however, are sometimes much more marked than would be 
 
528 INFECTIOUS DISEASES. 
 
 expected in view of the comparatively innocent character of the 
 disease. In this regard nothing is more instructive than influenza. 
 Even after the slight forms which have lasted but a few days, con- 
 valescence is very tedious. Weakness, asthenia, and incapacity for 
 work may persist for weeks or months. Finally, some of the symp- 
 toms of the stationary period may reappear. A convalescent from 
 typhoid fever will easily have diarrhea. A convalescent from a 
 thoracic affection will, upon the slightest cause, cough and have pain 
 in the side. 
 
 Evidently, the duration of convalescence varies according to the 
 nature, type, and gravity of the disease, and also according to the 
 age or previous condition of the subject. Aged individuals and 
 those who are already weakened require more time to be re-estab- 
 lished, and it may often be necessary for them to go to the country 
 or to a warm climate. 
 
 Convalescence may be interrupted by a variety of accidents. 
 Besides the nervous fevers already referred to, other causes may 
 produce a rise of temperature up to 102.2° or 104° F. (39° or 40° C). 
 After a (\&y or two the temperature again becomes normal. This 
 is often a process of abortive relapse. The disease, not being well 
 extinguished, recommences and is arrested by means of timely 
 medication or the natural defenses of the organism. In other 
 instances a septicemia is superadded to the primary disease. Some 
 authorities have even maintained that the relapses of typhoid fever 
 should be considered as infections of intestinal origin — i. e., that the 
 alterations of Peyer's patches, by lessening the means of defense, 
 permit the invasion of the economy by the habitual microbes of the 
 alimentary canal. 
 
 Febrile paroxysms connected with cutaneous suppurations may 
 also be observed. The alterations of the skin, like those just referred 
 to in the intestine, permit the pus cocci to produce abscesses o r boils. 
 At times an infection is produced in other organs. For example, 
 pneumonia may be observed during convalescence from any disease. 
 Lastly, in certain cases febrile paroxysms occur, which are ex- 
 plained by the aggravation of an antecedent chronic infection. For 
 example, in an individual who has suffered for a more or less con- 
 siderable period with a torpid or slow tuberculosis, and then con- 
 tracts measles, convalescence does not become duly established after 
 this intercurrent infection. He remains weak and suffering. He 
 has slight fever every night. The symptoms may thus evolve 
 
EVOLUTION OF INFECTIOUS DISEASES. 
 
 rapidly LowmkI ;i. f"«- i,i .* 1 1 termination, or, on the contrary, they 
 after a certain time be arrested and disappear, 
 
 Relapses and Recurrences. Convalescence may also be inter- 
 rupted by a relapse. In fact, in certain infections relapse is the 
 rule Such is the case in recurrent fever t and a particular form of 
 infectious icterus, improperly called Weil's di ea e. 
 
 Relapse is particularly frequenl in typhoid fever, influenza, and 
 bronchopneumonia. It is rare in lobar pneumonia, and exceptional 
 in other infections. Not infrequently il is caused by a fault of the 
 physician or of the patient. Alimentation may have been too rapid 
 or too abundant; the patient may have :s<>\ up too soon, or expo ed 
 himself to cold, and especially to fatigue. It is relatively easy to 
 treat a disease during the stationary period, but at the momenl of 
 convalescence the physician is often greatly embarrassed and requires 
 much tact and experience. 
 
 Relapse sometimes manifests itself in a slow and progressive 
 manner. More often it appears suddenly, even in the case of I v| >hoid 
 fever. In this disease the temperature reaches 102.2° or 104° F. 
 (39° or 40° C.) on the evening of the first day. In a general way, 
 relapses are less grave and of shorter duration than the primary 
 affection. There are many exceptions to this rule, however, and a 
 relapse may be more prolonged, graver, and even fatal. 
 
 In scarlatina we have never observed true relapses. We have 
 observed erythemata of convalescence, which we have already re- 
 ferred to, and which coexist with various infectious manifestations, a 
 knowledge of which singularly elucidates the significance. Such is 
 not the case with measles. At times a child presents a slight erup- 
 tion attended with slight fever and diarrhea. Measles is diag- 
 nosed, the symptoms resolve, and a few days later an eruption, 
 likewise accompanied by catarrh and fever, makes its appearance. 
 This second attack is generally more intense and better characterized 
 than the first. In one case in which the contagion was clearly 
 established the first attack occurred on the seventh day. and the 
 second renewal in due time, namely, on the twelfth day. The first 
 manifestation may, therefore, be considered as a sort of rubeoliform 
 rash; for it seems logical to admit that the eruption occurring at 
 the habitual moment is the true one. 
 
 Variola is not a disease in which relapses are observed. It must 
 be noted, however, that in certain instances some new pustules 
 may appear toward the twentieth day, especially upon the soles 
 
 34 
 
530 IXFECTIO US DISEASES. 
 
 of the feet. At all events, they are not numerous, and rapidly 
 disappear. 
 
 Relapses have often been observed in diphtheria. Here is a fine 
 example: The patient had been treated by serumtherapy. His 
 angina, which was of a quite serious character, was on the way to 
 recovery, when one morning he found the throat again covered 
 with pseudomembranes containing a large number of Loeffler's 
 bacilli. Although this patient had already received 60 c.c. of 
 serum, we gave two new injections of 30 c.c. each. The false 
 membranes were detached in four days, but the patient died from 
 diphtheritic paralysis. 
 
 Recurrences. A distinction has justly been established between 
 relapse and recurrence. Relapse means a new beginning of a disease 
 without a new infection. Recurrence is connected with a new 
 infection. In a good manj'- cases the distinction is easy. When a 
 person is attacked with typhoid fever or erysipelas after an interval 
 of fifteen or twenty years, such is evidently a case of recurrence. 
 When, however, the symptoms reappear at an early period, inter- 
 pretation becomes extremety difficult. Some individuals, particularly 
 women, have erysipelas everj^ month. Is such a case an example 
 of recurrence or of a relapse? It is impossible to answer, since we do 
 not know what period of time is required for the destruction of the 
 germ. 
 
 The present tendency is to increase the importance of relapses at 
 the expense of recurrences, and to admit that the microbes remain 
 inactive in the organs and tissues, but ever ready to assume the 
 offensive upon the slightest occasional cause. Indeed, it has even 
 been asserted that in most cases the recurrences of gonorrhea are but 
 relapses. In fact, the gonococcus persists during an almost indefinite 
 period of time in the urethra which it has once invaded. Erysipelas 
 and pneumonia are among the diseases which seem truly capable of 
 frequent recurrences. Recurrences of measles are quite common; 
 those of typhoid fever, smallpox, and scarlatina are very rare. 
 According to the information furnished by our patients, recurrences 
 of measles are observed in 14 per cent, of the cases in adults; that 
 of scarlatina is encountered once in a hundred cases. As to syphilis, 
 recurrence is altogether exceptional. Most of the cases cited as 
 examples of second chancre are accounted for by a confusion with 
 tertiary lesions of the genitals, which sometimes simulate a primary 
 lesion. 
 
EVOLUTION OF INFECTIOUS DI8EA8E8. :,.;l 
 
 Passage of Acute Infections to a Chronic Condition. Although 
 recovery is the normal termination of infectiou di ea e . there are 
 certain cases in which the evolution i prolonged beyond the u 
 limits. The disease is then said to have become chronic. 
 
 The duration of acute diseases Ins been arbitrarily fixed al forty 
 days. Beyond this term chronicity is uppo ed to be e tablished. 
 If the question be considered from a higher standpoint it will be 
 recognized that an essential difference between the two proc< 
 is furnished by the study of the evolution. Acute disease i- a 
 morbid process in a state of continuous modification. Each day 
 brings about a change which, though often but slightly marked, can 
 nevertheless be recognized by a careful examination. It will then 
 be noted that the organism is reacting— thai is, struggling with all 
 its forces to arrest and destroy the morbific cause; it is in revolt 
 against the invader. In a chronic disease the organism submits to 
 the yoke of the pathogenic agent, and seems to have no other ambi- 
 tion than to live with it. It hardly tries to circumscribe its progress. 
 It abandons itself, being incapable of continuing the battle. The 
 reason the condition of the patient is not more quickly reduced 
 is that the invader itself has become less active and aggressive. In 
 this manner a tacit agreement, as it were, is made between the 
 microbe and the organism, and the disease persists, undergoing only 
 extremely slow changes. 
 
 Therefore, an acute disease is distinguished by a lively and not 
 infrequently by a too energetic reaction. A chronic disease is 
 characterized by the absence, inefficiency, or the slowness of reac- 
 tion. 
 
 At times, however, the organism may for a moment recover its 
 energy. The result is acute attacks, often occurring without any 
 appreciable cause, and at times as a consequence of exposure to 
 cold, traumatism, or an intercurrent infection. Under these con- 
 ditions the pathogenic microbe makes a fresh attack, with the result 
 that the organism shakes off its torpidity. This acute spell may 
 be illy directed, undisciplined, and precipitate the morbid evolution, 
 and thus rapidly terminate in death. In other instances, after 
 having given rise to painful symptoms, it leads the organism to 
 recovery. A rebellious gonorrhea, for example, has been seen to 
 disappear after a new acute attack. 
 
 Medicine has attempted to imitate these natural procedures. 
 Irritant local applications may realize this indication. Koch's 
 
532 INFECTIOUS DISEASES. 
 
 tuberculin does not act otherwise. It whips, so to say, the torpid 
 evolution of chronic tuberculosis. 
 
 An acute process may become chronic without the production of 
 any notable changes. It stops at a given moment of its course. 
 This ma}' occur at the moment of aggravation as well as at the time 
 of improvement of the disease. The violent manifestations subside, 
 the reactions and pains cease, and in certain cases the symptoms are 
 so slight as to lead the patient to the belief that he is cured. Illus- 
 trations abound. They are drawn mostly from cases of non-specific 
 infections, mainly inflammations of organs — e. g., enteritis, nephritis, 
 and cystitis, which gradually pass into a chronic condition; also 
 various commonplace or specific suppurations. Gonorrheal ure- 
 thritis, for instance, is thus transformed, and often persists during 
 .an entire lifetime, occasioning no disturbance, and unknown even 
 to the patient. Finally, of the specific infections, we must especially 
 mention tuberculosis, which, after an acute attack, may follow a 
 .slow evolution. 
 
 In order to more closely study the evolution of chronic lesions 
 let us consider an abscess somewhat deeply situated. In its develop- 
 ment it produces various disturbances; then, when it is opened 
 to the exterior, the sjmrptoms cease. Suppuration, which is at first 
 very abundant, diminishes progressively. An early recovery may be 
 expected. At a certain moment, however, improvement is arrested, 
 and a fistula discharging a seropurulent fluid is established. There 
 is no longer any general or local reaction. This lesion, which be- 
 comes chronic, is borne by the organism without any apparent 
 inconvenience. However, at the moment when chronicity is estab- 
 lished, the discharge undergoes some modifications. It loses its 
 freely purulent character; it becomes more serous and more mucoid, 
 and at the same time the microbes diminish in number and virulence. 
 Failure to recover in such instances is often due to the presence of a 
 foreign body, a splinter, or a sequestrum in the focus; or else there 
 is diseased tissue at the bottom of the fistula. When it is possible 
 to intervene and extirpate or remove this inflammatory body, the 
 organism triumphs over the bacteria and the lesion heals. Thus 
 foreign bodies, although absolutely harmless when they are aseptic, 
 maintain an infection which would be cured in their absence. This 
 is a remarkable example of pathogenic association. 
 
 The microbe, although attenuated, is not absolutely inoffensive 
 in such chronic conditions. It seems even that its feeble pathogenic 
 
EVOLUTION OF fNFECTIOUS DI8EA8E8. 
 
 potency depends mainly upon some protective powi d by the 
 
 w;i,ll of the morbid focus. Chauveau ha hown thai the pu ol b 
 no ton which product's no di turbance i virulent. It 8 particle "f 
 it be inoculated into another poinl of the economy, di turbances 
 
 are produced. The pus was endured only in itfl old foCU , 
 
 In cases of chronic suppuration fistula may from time to time 
 become occluded. The subjacenl focus i then filled with pue and 
 increases in volume; h becomes painful and give ri e to f( 
 After an artificial or natural opening the lesion re nine itc 
 and chronic course. In oilier instances the fistula becomes closed; 
 it appears to be healed; as no 3ymptom is any longer apparent. 
 For months or years the lesion gives rise to no disturbance what* 
 Mien the focus, which seemed extinguished, ie again kindled and a 
 new attack is produced. Such a course is produced especially in 
 cases of osteomyelitis, where a sequestrum may give rise to very 
 tardy disturbances at considerable intervals. The microbe slumbers 
 for years as an absolutely inoffensive guest. An occasional, often 
 unnoticeable, cause enables it to recover a certain degree of viru- 
 lence and to arouse inflammatory reactions. 
 
 A similar evolution is sometimes observed after typhoid fever. 
 This disease never passes into a chronic state, but the microbe that 
 causes it may become localized at certain points, notably in the 
 bone-marrow, and thus call forth a slow inflammation which termi- 
 nates, after several months, in a focus of osteomyelitis. Bacterio- 
 logical examination demonstrates the presence of Eberth's bacillus 
 therein. In this case the acute disease ends in a chronic pr< 
 quite different from what it had originally been. 
 
 We can find highly interesting illustrations in the history of ul< 
 Let us consider, for example, the varicose ulcer. A slight lesion, an 
 abscess, a pustule, a simple abrasion having induced an infection 
 so mild that no symptom is produced, and the existence of which we 
 admit simply by induction, is the starting point. Reparation is not 
 effected because the tissues were altered. Their nutrition was pro- 
 foundly disturbed by the varicose condition of the vein-. The skin 
 had become hard, brownish, and sometimes the seat of eczema. 
 Therefore, the little lesion sufficed to produce a chronic affection in 
 the suffering tissue. The same explanation is applicable to ulcer- 
 ating dermosynovitis. This is a trophic lesion induced by an ordi- 
 nary cause or a slight infection, and it develops and persists because 
 nutrition is profoundly disturbed by nervous lesions. 
 
534 / -V I'ECTIO US DISEA SES. 
 
 Experimentation confirms the data of clinical observation by 
 demonstrating that section of sensory nerves hinders considerably 
 the process of repair. For example, division of the sciatic nerve 
 in a guinea-pig is often followed by ulcerations in the foot operated 
 upon ; but if care be taken to protect the limb by means of a sort 
 of plaster shoe, infection is prevented, and no nutritive disturbance 
 appears. 
 
 The same is true of ulcers of mucous membranes. A common- 
 1 dace lesion, in most cases of infectious origin, may serve as a starting 
 point for an ulcer of the esophagus, duodenum, and especially of 
 the stomach. Ulcer of the stomach develops in hyperchlorhydric 
 dyspeptics. The excess of acid hinders reparation. Filhene has 
 given an experimental demonstration of this pathogenesis: Two 
 rabbits received considerable doses of arsenic subcutaneously. In 
 one of them, kept as a control, gastric ulcers developed ; in another, 
 to which bicarbonate of soda was administered to neutralize the 
 gastric juice, no lesion was produced. 
 
 Although the organism plays a very important part in the develop- 
 ment of ulcers, we must recognize that the lesion is sometimes 
 dependent upon the nature of the pathogenic agent, its degree of 
 virulence, and the point at which it is developed. The ulcerations 
 of tuberculosis, glanders, and syphilis and phagedenic lesions belong 
 to this group. The influence of the organism, without being abso- 
 lutely null, is in such cases considerably reduced. 
 
 An acute lesion may pass into a chronic state under a form rela- 
 tively favorable, namely, induration. In such instances the organism 
 succeeds in completely destroying the pathogenic agent, but the 
 ulcerations produced are too profound to admit of perfect reparation. 
 The tissue, instead of returning to its primary condition, is replaced 
 by a newly formed fibrous production. This termination is observed 
 in superficial lesions, in certain abscesses, and in adenopathies; but 
 it is particularly important in deeply situated tissues and organs. 
 In this manner cicatrices are produced which, when located in the 
 mucous membranes, cause deformity and embarrass their normal 
 action. When located in such passages as the esophagus or the 
 urethra they result in stricture; in the viscera, such as the heart, 
 liver, or kidneys, they produce sclerosis. In these cases the chronic 
 process differs completely from the acute. As we have shown in 
 treating of sclerosis, the process of repair remedies the first disturb- 
 ances, but creates ahinderance to the regular activity of the organs. 
 
EVOLUTION OF INFECTIOUS DI8EA8E8. 
 
 The chronic processes, the mechani m of which we have indicated 
 above, undergo no modification or evolve lowly eithei 
 recovery or toward death, [nbothin fcance change ending in one 
 or the other of these two termination) are produced either in an 
 insidious manner, or else the chronic course i interrupted by an 
 acute attack which leads, as the case may be, to rec r to 
 
 death, or, as a third alternative, leaves the organism in the same 
 condition as before its occurrence. 
 
 Death. When an acute disease ends in death the fatal termination 
 may occur suddenly, in an unexpected manner, or 3lowly and pro- 
 gressively, preceded 1 >% more or less prolonged agony, [f oecr< 
 is performed, macroscopic or microscopic lesion ometimes 
 
 found. In olher eases post-mortem examination gives a negative 
 result. By taking into account the various results which may be 
 obtained the causes of death may be divided into three groupe: 
 1. Mechanical disorders or barriers. 2. Lesions of an important 
 organ. 3. General infection or intoxie.it ion. 
 
 As a striking illustration of the mechanism of death by a mechan- 
 ical cause we may mention diphtheritic laryngitis. The pseudo- 
 membrane developing in the larynx embarrasses the passage of air, 
 and may cause death, partly through the reflex spasm which it 
 excites. Likewise, a phlegmon taking its origin in certain regions, 
 may, by its size or by the edema surrounding it, mechanically induce 
 a fatal termination. In these examples death evidently results from 
 the obstacle created by the lesion, since if the false membrane be 
 detached or the circulation of air be re-established through intubation 
 or tracheotomy, or the phlegmon be opened, the disorders disappear 
 immediately. 
 
 The local lesion which thus endangers life is not, however, the 
 work of a microbe, but is due to a reaction of the organism, which 
 seems to fight against itself. But if Ave more closely investigate 
 the succession of the phenomena, we understand that the organism 
 has produced a false membrane or a purulent focus in order to pre- 
 vent general impregnation. The lesion thus created was designed 
 to circumscribe the morbid process and to oppose the penetration 
 of microbes or their toxins. The organism, however, is not always 
 capable of proportioning its efforts to the work required. In a good 
 many instances reaction exceeds the end. A microbe penetrating 
 into the lungs induces an acute pulmonary congestion. The vessels 
 dilate in order to facilitate the escape of fluids and cells which will 
 
536 I MECTIOUS DISEASES. 
 
 arrest the development of the parasite. The reactionary pheno- 
 mena, however, are often too intense, and may induce grave accidents. 
 In other cases the microbe reaches the surface of the lung and 
 irritates the pleura, which then secretes a fluid that is often so 
 excessive in amount as to necessitate surgical intervention for its 
 evacuation. .Lastly, in certain instances reaction is not too strong. 
 It is truly beneficial, but it is produced in particularly delicate 
 localities, and for that reason may prove dangerous. Such, for 
 example, are congestion, edema, and abscess produced in the brain. 
 Under these various conditions the organism endeavors to remedy the 
 immediate disorders, but it mobilizes too great a number of cells or 
 gives issue to an excessive amount of fluid. 
 
 Under such circumstances, therefore, therapeutic measures should 
 be directed to the organism itself, so as to moderate the morbid 
 reaction and check the intense congestion which threatens to give 
 rise to asphyxia by reason of its intensity. In other instances, on 
 the contrary, we must assist the organism in its efforts to accomplish 
 that part of its work which it is unable to do alone. Puncture of a 
 pleural collection or the evacuation of a cerebral abscess is not 
 medication against nature, but a complementary method aiding the 
 insufficiency of natural means. 
 
 As morbid reactions may, on the one hand, endanger life by their 
 excessive intensity, on the other, their insufficiency may be a new 
 cause of disorders. When a microbe develops it gives rise to sub- 
 stances which destroy the surrounding cells. The destroyed ele- 
 ments are liquefied and, when possible, thrown out. When the 
 organism fails to remedy the imminent accidents by the various 
 means at its disposal, notably through the accumulation of wander- 
 ing cells, or if the leucocytes be killed as they arrive at the point of 
 invasion, a more or less complete destruction of the affected tissue 
 will result. Gradually extending, necrobiosis may reach a vessel, 
 and, if the course of the process is rapid, a grave or fatal hemorrhage 
 occurs before a clot is formed. In other cases an important cavity 
 is opened. For instance, the wall of the intestine may be perforated. 
 In these various instances lesions which are apparently sufficient 
 to account for death are revealed by the necropsy. 
 
 As a result of anatomico-pathological discoveries we have become 
 so accustomed to attach an exaggerated importance to anatomical 
 lesions that our minds are satisfied when the necropsy detects a 
 morbid focus in some important organ. Let us take, for example, 
 
EVOLUTION OF INFECTIOUS DISEASES. :,.;? 
 
 the case of a child dead of tneai les. During life a murmur 
 
 found at the base of one lung, and on opening the cadaver a I 
 of bronchopneumonia is discovered at this point. The mechani m 
 of death in this instance appears to be readily conceivable; yel 
 on a little reflection, it will be acknowledged thai it i hardly 
 possible to attribute the filial termination to a lei ion <> i mall ai not 
 to hinder hematosis t<> any ,L r n:ii degree. 'Mi'' 3ame rea oning is 
 applicable to oilier organs as well in those cases in which multiple 
 lesions an; found. In acute miliary inlierculo i , when the tubercles 
 have invaded the serous system only, why has the individual died? 
 Pushing the question further, it may be asked: Why has he suc- 
 cumbed even when the multiple granules have invaded the riscera? 
 There generally remains sufficienl intact parenchyma to assure the 
 function of the organ. It is here that modern science inter 
 and rightly proclaims the r61e of toxins secreted in the dia 
 organs and leads to the admission that death is due to poisoning. 
 This interpretation is confirmed by those cases in which no manifest 
 lesions are revealed by the necropsy. 
 
 Let us suppose an individual succumbing to anthrax. The blood 
 is disintegrated, dark, and stick)', and the spleen is voluminous and 
 the other viscera congested. At times small visceral ecchymoses 
 only are met with. This is evidently somewhat disappointing. On 
 examining, however, a drop of the blood or a particle of the organs 
 under the microscope, innumerable bacilli are observed, and thus 
 some light is shed on the problem. Death is due to general infection. 
 Toussaint used to say it was due to an obstruction of the capillaries 
 by the bacilli. But this invasion and dissemination of the foreign 
 elements does not seem to be sufficient to explain the fatal termin- 
 ation. It is neither by crowding the vessels nor by abstraction of 
 oxygen or of the materials necessary for cellular renovation that the 
 bacteria have destroyed life, but by secreting soluble substances 
 capable of disturbing the activity of the cells. 
 
 This interpretation, which may seem contestable as regards 
 anthrax, is the only one admissible in reference to those diseases the 
 pathogenic agent of which is localized at a certain point of the 
 organism. In diphtheria, gaseous gangrene, and cholera the microbes 
 do not invade the economy. They remain localized at a point or 
 confined to the digestive canal. Death cannot, therefore, be attri- 
 buted to any other cause than the soluble substances engendered by 
 the micro-organisms. 
 
538 IXFECTIO US DISEASES. 
 
 It is not enough, however, to say that death is the result of an 
 intoxication. We must endeavor to indicate more accurately the 
 mechanism of a fatal termination. In certain cases lesions are found 
 which of themselves would be sufficient to endanger life. For 
 example, the autopsy reveals degeneration of the liver and kidneys, 
 myocarditis/ or hemorrhages of the suprarenal capsules. Chemical 
 analysis shows the diminution or even the absence of glycogen in the 
 liver, and microscopical examination demonstrates the presence of 
 cellular lesions in most of the organs. It may then be asked whether 
 these multiform alterations have not played a part in bringing about 
 the final result and whether the autointoxication arising from organic 
 insufficiency has not been added to the microbic intoxication. This, 
 however, would only displace the problem, for it is at all events to be 
 recognized that the cellular lesions are, in certain cases, too limited 
 to exert a notable influence. We are thus brought again to admit 
 a toxic action. This action, however, is not immediate. The 
 microbic poisons do not kill rapidly, but a certain length of time 
 elapses between the moment of their introduction and the instant 
 when the first responsive manifestations appear. Instead of at once 
 arresting the nutritive activity which essentially characterizes life, 
 the microbic toxins disturb nutrition by adulterating the intercellular 
 medium. Whether the poison itself modifies this medium, or whether 
 the secondary products originating under the influence of the toxins 
 act as a ferment, is a matter of little importance. What is an 
 important fact, however, is that even when a fatal dose is at once 
 introduced into a vein, the animal dies only after the lapse of 
 several hours. This means that a whole series of secondary modi- 
 fications are produced through the influence of the toxin. 
 
 We are thus led to consider not the total death, but the individual 
 death of the parts of the organism — i. e., of the cells. It might be 
 supposed that, under the influence of toxins, nutrition is equally 
 perverted in all parts of the organism; but such a conception is 
 hardly admissible. The cells are disturbed according to a fairly 
 determined order — those performing the highest functions are 
 affected first. The nerve cells occupj' the highest position, and 
 experimentation in accordance with clinical facts shows that it is 
 upon them that the deleterious action of toxins is in most cases 
 exerted. The dynamic state of the nerve cells being thus modified, 
 it is comprehensible that an occasional cause, by producing in them 
 an abnormal agitation, may induce sudden or speedy death. Other- 
 
EVOLUTION OF TNFEOTIOV DI8E I i:s. 539 
 
 wise, the fatal termination Bupervenei gradually a the re nil of 
 progressive weakening of metabolism. In order to admit tl 
 different conceptions withoul reservation we should be exactly 
 informed as to the functional state of the variou parts of the 
 organism at the moment of death. Bere i a mo I difficult question 
 which has not as yet been the subject of experimental stui 
 
 In brief, death as a result of infection i- death from intoxication. 
 
 The inicrol>ic poisons ;iceiiiniil;iie in the organism and hinder or 
 prevent normal cellular life. Possibly they act I)}' forming combina- 
 tions with the cellular protoplasm. Ii is more probable, however, 
 that they affect the cells by adulterating the intercellular medium. 
 The result is a series of functional disturbances which cause death, 
 and at the necropsy no lesion, or almost none, is found even under 
 the microscope. If lesions are met with they are too small to 
 account for the fatal termination. If life i> prolonged, however, 
 functional disorders induce anatomie:il modifications. Thus im- 
 portant cellular lesions are secondarily produced which play an 
 important role in the mechanism of deferred death. Here, however, 
 the question is no longer one of infection, but of organic lesions 
 evolving on their own account and deriving no particular character 
 from their origin. 
 
 It is well here to call attention to a mode of termination which is 
 not rare in young children and the aged. The patients recover 
 from their infection and seem to be entering upon convalescence. 
 Such is not the case, however; general debility rapidly progresses, 
 and emaciation becomes more pronounced day after day. Then the 
 intelligence becomes dull; eschars make their appearance, and at 
 times slight fever manifests itself in the evening. After a period 
 of time, varying from eight to fifteen daj r s, death supervenes without 
 any other symptom, as a result of post-infectious cachexia. Such 
 an evolution is observed after erysipelas. We may. in this con- 
 nection, report the case of a man, sixty years of age, who entered our 
 hospital for an erysipelas of the face on the twentieth da}' of its 
 evolution. On the day of admission his cutaneous inflammation 
 still occupied the nose, forehead, cheeks, eyelids and scalp. The 
 temperature was 103.5° F. (39.8° C), accompanied by slight delirium. 
 The urine contained no albumin, the liver was not swollen. Two 
 days after the temperature fell to 101.7° F. (38.5° C), and five days 
 after his admission it returned to normal. He seemed to have 
 recovered from the erysipelas, but his general state remained quite 
 
540 INFECTIO US DISEASES. 
 
 unsatisfactory. The temperature continued to fluctuate about 
 98.5° F. (37° C), and he was becoming cachectic quite rapidly, and 
 thirteen days after his admission he died. For the last eight days 
 his temperature had been normal, and on the day of death it was- 
 only 98.5° F. (36.6° C). The necropsy revealed no special lesion 
 capable of explaining the fatal termination. The lungs, particularly 
 the right lung, were congested at the bases. The heart presented a. 
 slight fatty condition. The mitral valve was thickened, the aorta 
 slightly dilated and atheromatous. The kidneys were also sur- 
 rounded with a thick layer of fat. The liver presented the color 
 of chamois leather, and on section, violet. The weight of all these 
 organs was less than normal. The cause of this post-infectious 
 cachexia is probably chargeable to a previous insufficiency of the 
 organs concerned in the protection of the organism against infections, 
 notably the kidneys and the liver. The toxins elaborated by the 
 pathogenic microbe are not destroyed or eliminated with gratifying 
 rapidity; hence impregnation is more profound than is indicated 
 by the benign character of the infectious lesion, and its effects con- 
 tinue after apparent recovery. The situation is the same as in 
 certain animals brutally inoculated with a large dose of an attenuated 
 microbe. If the microbe is highly virulent, the animal dies from 
 an acute septicemia. If moderately virulent, it is destroyed, but 
 the toxins which are introduced with the pathogenic agent and 
 those which are elaborated by it within the organism continue their 
 action and give rise to a fatal cachexia. This is what happens 
 notably with the streptococcus. In fact, we have shown that intra- 
 venous injection of attenuated cultures seems to produce no symp- 
 toms, and then, after a few days, the animals grow thin and succumb 
 in from fifteen to twenty or thirty days after the inoculation, in a 
 state of an extraordinary degree of cachexia and emaciation. At 
 this moment the microbe has disappeared from the organism and 
 cultures made from the organs remain sterile. 
 
(Ml A PTEE XVI] I. 
 THE CONSEQUENCES OF INI EC1 EON. 
 
 Apparent and Real Recovery. Reparation of Traumatic [> Ion ando • t ir,,j ^ 
 
 Lesions. Comparison between The e Two Proci i I ol the Diffei 
 
 Post-infectious Visceropathies. Their Mechanism. Their B volution, Epithelial 
 and [nterstitial Visceropathies. [mportance ol Vi ceral Sclera Lficance of 
 
 SclcroscH. 
 
 Can an infection be cured completely? The disease having 
 terminated, can the organism return to its former state? Can all 
 the disorders that were produced disappear and all the lesions be 
 
 repaired? From a practical standpoint there is no doubl as to the 
 answer to this question. After an infection, even though it be grave 
 or prolonged, health is re-established; the patient is conscious 
 having returned to his normal state; years may elapse, and life may 
 come to an end without the slightest manifestation having been 
 observed which might rightly be traced to the previous infection. 
 If, however, the question be considered from a higher point of view 
 a quite different solution is reached. Complete restoration of the 
 economy to its previous state seems to us impossible. Recovery 
 being clue to modifications in the fluids and the fluids being cellular 
 secretions, it is, of course, necessary for changes to be produced in 
 the mode of life — i. c, in the nutrition of the cells, in order that 
 the infection may be overcome. If at all possible, the return of the 
 organism to its normal nutritive mode is to be gradually effected. 
 Will such be the case in every instance? Observation teaches us 
 that, in a great number of cases, nutrition is profoundly and defi- 
 nitely modified. The variations in the degree of fatness of the 
 individuals are, from this standpoint, quite demonstrative. In some 
 cases obesity, in others an excessive emaciation, is the permanent 
 result following an infectious disease. These changes are readily 
 appreciable after acute infections, such as typhoid fever, or even 
 after recovery from a chronic infection such as tuberculosis. In 
 some of these cases the post-infectious modifications are favorable. 
 The infection having, so to say, whipped the organism to greater 
 activity, improves the health, with the result that certain ill-deter- 
 
54:2 I M'ECTIOUS DISEASES. 
 
 mined disturbances, often attributed to diathetic conditions, dis- 
 appear, and previous chronic, notably nervous, affections are cured. 
 The reverse effect, however, is unfortunately more frequent. The 
 acute disease often proves to be the occasional cause of a series of 
 consecutive disturbances and various neuroses. In certain cases the 
 consequences' of infection are so pronounced as to be noticeable 
 even by the most superficial observers. Not infrequently, however, 
 they easily escape notice and are very difficult of interpretation. 
 As a matter of fact, these consecutive changes are sometimes so 
 slight that we are compelled to assume their existence by induction 
 rather than by observation. Moreover, they may make their appear- 
 ance very tardily; months and years elapse, and when symptoms 
 become apparent after such long periods some hesitation is felt 
 in connecting them with their true cause. 
 
 We must now successively consider the consequences of local 
 lesions produced by toxins and general disturbances which may 
 develop under their influence. The local action of toxins is ex- 
 pressed, as is known, b}' degenerations or cellular necrobioses. The 
 most clearly differentiated elements, which perform the highest 
 functions but which are also the most delicate, are first attacked. 
 The cells constituting the tissues and organs are not all similar. 
 All of them do not have the same force of resistance ; hence, in the 
 presence of the same morbific cause, they do not all react in the 
 same manner. Certain cells succumb, while some undergo alter- 
 ations, some remain intact, and still others present evident signs 
 of excitation and may abundantly proliferate. The ulterior fate 
 of the organ differs according to the state of these variously affected 
 cells. Those which have begun to proliferate may serve to repair 
 and replace those which, being less resistant, have degenerated or 
 been killed. A perfect reparation might, therefore, be expected. 
 In reality, however, such is not the case. There is a curious differ- 
 ence between the reparation of traumatic and of infectious lesions. 
 When a part of an organ is excised, complete restoration is possible. 
 Let us suppose that even a large piece of the liver is cut off. If 
 the experiment is well conducted, if infection is avoided, repair 
 will be effected and newly formed cellular tissue will fill up the 
 deficit. If, on the contrary, the cellular destruction is the work of 
 infection, reparation will not be as complete. A great number of 
 the diseased cells will be replaced not by similar cells, but by 
 sclerotic tissue. Microbic as well as exogenic poisons are capable 
 
THE CONSEQUENCES OF INFECTION. :,].; 
 
 of exerting the same influence. It verj Bmall doses of pbosphorue 
 are administered to an animal, degeneration of its hepatic cell is 
 produced, [f the employmenl of the poison i then Btopped, 
 cicatrization takes place i. e. } a proliferation of connective ti 
 which replaces the dead cells. 
 
 Not infrequently, however, infection as well at intoxication 
 destroys only a small number of cells. Their replacement would, 
 
 therefore, seem easier Ih.'in in c;ises in which traumatil m hfl 
 
 1,1 in dis.'i|)|)e.'ir:i.nce of one fourth or one-third of the gland. I il nol 
 also known that extirpated organs have completely regenerated 
 
 when a small fragment had been left? In such cases reproduction 
 of nearly all the cells and of the primary type has taken place, 
 although the task of reparation seemed far more difficult than in 
 the case in which destruction is partial and disseminated. This 
 fact proves that sclerosis is not, as might have been believed, a 
 tissue taking the place of destroyed cells. It is necessary that this 
 destruction should present certain particular characters. This fact 
 may eventually be interpreted in several ways. The simplest 
 explanation seems to be the following: In the case of traumatism 
 the excised cells are far more numerous, but the remaining cells are 
 sound; they possess normal activity: they proliferate and occupy 
 the place left vacant. On the other hand, in the case of infection — 
 and what we say of infection is applicable to intoxication — the 
 soluble substances impregnate the whole gland. The cells which 
 first receive the poison or those which are less resistant, degenerate 
 or are killed; others, although they survive and are apparently 
 normal, do not, however, completely escape the influence of the 
 morbific cause. Their activity is, therefore, disturbed, and, although 
 the modification is not expressed by any lesion appreciable under 
 the microscope, it is safe to assume that this modification is sufficient 
 to hinder proliferation. It is thus conceivable that reparation is 
 the more difficult and incomplete the more profound is infection. 
 We may repeat once more: sclerosis is produced not because the 
 destroyed cells are too large in number (infection never causes the 
 disappearance of as many of them as does traumatism), it occurs 
 simply because the remaining cells are not normal. The same inter- 
 pretation is applicable to those cases in which the focus of destruction 
 is well limited. The neighboring cells are alone disturbed, but these 
 are precisely the cells which should proliferate and are incapable 
 of so doing. It is, therefore, intelligible that an infectious lesion. 
 
544 IXFECTIO US DISEASES. 
 
 however small, may produce more extensive disorders than a far 
 more considerable traumatic lesion. The result is that reparation 
 is less perfect. 
 
 If the lesion is well localized and not very extensive, the resulting 
 cicatrices may sometimes produce no disturbance. Such is not 
 always the case, however, as may be seen from the frequency of 
 strictures occurring in the urethra in consequence of gonorrhea. 
 This illustration elucidates the history of organic lesions. Viscer- 
 opathies have long been considered as diseases. Imbued with the 
 false idea of morbid spontaneousness, physicians believed they had 
 solved the nosological problem when they found a cardiac, renal, 
 hepatic, or cerebral lesion. For instance, a mitral insufficiency was 
 detected, and if rheumatism was not found in the antecedents of 
 the patient, no investigation was made as to the cause of the lesion. 
 At present we know that every disease is caused by an external 
 agent and that visceral lesions are nothing else than the conse- 
 quences of previous diseases. The process occurring in the organs, 
 though of a more complex character, is none the less comparable to 
 that occurring in the urethra. 
 
 The pathological anatomy of acute infections has shown us that 
 cellular lesions are far more intense and diffuse than was once 
 believed. The systematic study pursued in recent years with regard 
 to the viscera and the tissues during infections leads us to the 
 question how any process of repair, even incomplete, is still possible. 
 It is true that when visceral lesions are too extensive, death super- 
 venes during the acute stage of the disease, and less frequently it 
 occurs after the process seems to be at an end. We have already 
 shown how the aged thus succumb to a post-infectious cachexia. 
 At a less advanced stage, however, a return to health seems to be 
 effected. The most careful examination reveals no appreciable 
 disorder, and, for a number of years, the organism seems to have 
 returned to a perfectly sound state. Nevertheless, a silent evolution 
 is going on, ending in visceral sclerosis. The lesion may exist for 
 a very long period of time without being expressed by any symptom. 
 This is owing to the fact that the organs contain a far greater number 
 of cells than is necessary for life. It may be assumed that 40 to 50 
 per cent, of the glandular tissues may be suppressed without bringing 
 about any disturbance. One-third of the liver, a whole kidney, even 
 a whole lung, may be extirpated without great inconvenience. It 
 is therefore intelligible that a visceral lesion may evolve during years 
 
THE CONSEQUENCES OF INFECTION. :,\: t 
 
 without producing any symptom. The affection i in a tate of 
 latency, and will be revealed later, either by signs detected by 
 methodic exploration or |>y the fact thai the un table equilibrium 
 of the sanitary condition resulting from the visceropathy i dit turbed 
 l>y some intercurrent and maybe unimportanl cause. The ymp- 
 toms may thus make their appearance suddenly or progre ively 
 on the occasion of a cold, traumatism, fatigue, an error of diet, or 
 a new infection. It must also he remembered thai , in certain C 
 the visceral affection always remains in a state of latency, and will 
 be disclosed only at the necropsy. In other instances the visceral 
 affection is revealed in a sudden manner, causing sudden death. 
 
 The necropsy in such cases surprises the physician by revealing 
 profound lesions which had remained so long in a state of latency 
 without manifesting any clinical disturbances. 
 
 The organic affections which appear thus as the consequence 
 notably of previous infectious diseases, may be divided into two 
 great classes. In one of them epithelial lesions predominate; in the 
 other, sclerotic lesions. Hence, the classical division of affections 
 into parenchymatous and interstitial, a division which seems to be 
 justified both by clinical observation and pathological anatomy. ( hi 
 investigating, however, the causes which have led to the develop- 
 ment of these two distinct processes, we find the same etiology 
 and the same infections responsible for both kinds of changes. 
 We are thus led to the idea that visceral lesions are everywhere and 
 always at first characterized by a diffuse inflammation, and this 
 idea finds a solid basis in anatomico-pathological studies. In view 
 of the facts hitherto reported, we reach the conclusion that microbic 
 toxins first give rise to epithelial degeneration, which is soon followed 
 by inflammatory, epithelial, and interstitial reactions. At this 
 moment the process is diffuse. Later, when the acute phenomena 
 have passed, a chronic evolution takes place in either direction. 
 One of the elements predominates, and the result of the processes 
 which were at first identical, is either a parenchymatous or a sclerotic 
 inflammation. It is more difficult to determine the causes which 
 intervene and direct the anatomical evolution. Two factors, as 
 always, may be admitted: the toxins induce degenerative o r simply 
 irritative lesions — i. c, cause the death of the highly organized cells or 
 stimulate the proliferation, according to (a) the degree of resistance 
 of the subject, or (6) the degree of activity of the microbe. It is 
 conceivable that, in the former instance, the elements that are killed 
 
 35 
 
546 INFECTIOUS DISEASES. 
 
 may not be replaced by any other than connective tissue. In the 
 latter case, on the contrary, the perishing cells are smaller in number 
 and the vacancies left are filled up by the neighboring cells the 
 activity of which is increased. Reparation would therefore be 
 perfect, if there was only cellula r hyperactivity. But pathologic 
 histology establishes that along with this overactivity there is a 
 nutritive deviation. In this connection our researches concerning 
 the modifications of the thyroid gland are quite demonstrative. 
 We have shown that, in the most varied infections, the following 
 three phenomena are always present : death of some cells and degen- 
 eration or increased activity of certain others. In some cases the 
 two last processes coexist; the nucleus is multiplied while the pro- 
 toplasm degenerates. But the modification of the secreted fluid 
 proves the profound disorder of the cells. Colloid matter presents 
 reactions which enable us to follow under the microscope the histo- 
 chemical changes occurring in it. It is very easy to thus prove the 
 functional disturbances. It is therefore conceivable that when the 
 infection is terminated, three different processes may ensue: In 
 some cases degeneration will predominate, in others proliferative 
 overactivity, and in still other cases sclerosis will replace the dead 
 elements. In the last instance the process has been too intense; 
 the cells in the neighborhood of those that have succumbed are 
 themselves too much affected to proliferate and occupy their place. 
 Sclerosis, therefore, seems to us to be the termination of intense, 
 extensive, or prolonged inflammatory processes. Let us again take 
 urethral stricture as an example. In cases of gonorrhea occurring 
 only once and having been rapidly cured, stricture is exceptional. 
 The cells adjacent to those destroyed have succeeded in taking the 
 place of the dead. In gonorrheas of long duration stricture is the 
 rule, since the cells destroyed are too large in number, and those 
 surrounding them are too deeply affected to establish normal rela- 
 tions. A cicatrix, that is, sclerotic tissue, is, therefore, produced. 
 
 The sclerotic tissue destined to fill up the vacancies left by the 
 dead cells must be considered as a tissue of replacement. Whether 
 it be developed, as is generally held to be the case, at the expense 
 of the cells of connective tissue, or is progressively produced by 
 hypertrophy of pre-existing fibres, as seems to be the case in certain 
 instances, it is always destined to remedy immediate accidents. 
 This sufficiently indicates that we reject the existence of primary 
 scleroses. The connective tissue alteration is always preceded by a 
 
THE CONSEQUENCES OF INFECTION, r,\7 
 
 lesion of the more highly differentiated elements. In other word . 
 scleroses are always of epithelial origin. Lei u cod ider an organ 
 in which scleroses have often been studied) for example the kidney. 
 An attempl was made to admit two kinds of nephrite , namely, 
 epithelial and interstitial, the latter indicating clerosi from the 
 first. A special etiology, pathogenesis, and symptomatology had 
 been assigned to each of these two affections. A change was little 
 by little produced in this conception. It was recognized thai '-very 
 case of nephritis begins in the more highly organized element* and 
 that the process soon extends; so thai nephritis is primarily diffuse, 
 and Inter on evolves toward various anatomico-clinical type-, the 
 two extremes of which are represented by the large white kidney, 
 in which the epithelial lesions predominate, and by the small red 
 kidney, in which the sclerotic lesions prevail. Thus are constituted 
 sharply distinguished affections which must be separated in ana- 
 tomical and clinical descriptions. The point of departure, however, 
 is the same in all. The final result differs because all organisms 
 are not similar. 
 
 The same conception is applicable to hepatic cirrhoses. The 
 origin must be looked for in a primary lesion of the hepatic or the 
 biliary cells. The idea of connecting atrophic cirrhosis with a 
 primary alteration of the portal vein, w r hich is still held by some 
 authorities, is based upon incomplete anatomical study. It is at 
 present demonstrated that the process is not as systematic a? was 
 once believed. Sclerosis develops simultaneously around the portal 
 and suprahepatic veins and forms bands so irregular as to defy all 
 topographical description. On the other hand, a sclerotic lesion is 
 never seen to diffuse toward adjacent parts. It is, therefore, prob- 
 able that poisons or microbes circulating in the portal vein produce 
 primary alterations in the hepatic cells. The marginal cells are 
 the most profoundly influenced and the first to be affected; next 
 the central cells, which the blood reaches after passing through the 
 capillaries. Thus the topography of the sclerotic lesions is explained. 
 In most cases the venous alterations seem to be of a secondary 
 character. It must, however, be admitted that they may some- 
 times be primary. They may then produce sclerosis, because the 
 circulatory disorders disturb the nutrition of the cells. Even in 
 these cases the sclerotic process is not an irradiation of the peri- 
 phlebitis. It is consecutive to a degenerative alteration of the 
 hepatic cells. 
 
548 INFECTIOUS DISEASES. 
 
 It would be easy to present analogous considerations in reference 
 to other glands and various tissues, and thus show that sclerosis is 
 always designed to fill up vacancies. 
 
 Sclerosis of the nervous tissue seemed, for a time, to be an excep- 
 tion. In reality there has been an error of interpretation in this 
 matter. It is at present known that scleroses of the neuroglia do 
 not enter into the group of true scleroses. The neuroglia does not 
 represent connective tissue. It is an ectodermic production, a 
 nervous tissue. It is not strange if systematic lesions not obe3dng 
 the rules above reported are produced in this tissue. The process 
 is a special one quite different from true or mesodermic sclerosis. 
 
 Although infectious diseases influence the entire economy, the 
 lesions resulting from this influence must be diffuse. Generalized 
 sclerosis affecting the tissues and viscera are observed in certain 
 instances. The ensemble of these facts is known under the name 
 of arteriosclerosis. With or without good reason, a predominating 
 part is thus attributed to the arterial system in the genesis of these 
 disorders. The conception is not groundless. The microbic toxins 
 carried by the blood current must first impregnate the vascular 
 walls. Even when arteriosclerosis is generalized, however, it pre- 
 dominates at certain points. Hence a cardio-aortic, a renal, and a 
 cerebral sclerosis have been described. Finally, in a certain number 
 of cases, the process seems to be different, although I hold it to be 
 of the same order; the arteries are slightly, if at all, affected; a 
 single viscus is injured. This single visceral sclerosis must be 
 classed with multiple organic sclerosis. It is always the same 
 process, progressing in an identical manner and depending upon a 
 similar cause. It is in all cases the result of toxi-infection. It is 
 intelligible, however, that the morbid localizations and post-infectious 
 sequels may differ according to the intensity of the infectious process, 
 the responsive aptitudes, and the inborn or acquired predisposition 
 of the individual. This is sufficient indication that we do not class 
 visceral scleroses with arteriosclerosis. We believe that the two 
 orders of lesions progressing side by side depend upon a common 
 cause. Sclerosis of the arteries and that of the viscera are two 
 simultaneous effects of the same cause. The bond existing between 
 arteriosclerosis and visceral scleroses is not one of subordination 
 of the latter to the former. The frequency of this association is 
 due to the action of the same cause upon similar tissues. To isolate 
 the arterial alterations from the entire process in order to make of 
 
THE CONSEQUENCES OF INFECTION. 549 
 
 these the cause of visceral alterations is to make an artificial dis- 
 sociation which is in nowise necessary for explaining the patho- 
 genesis of these Lesions. 
 
 Scleroses, whether arterial or visceral, may begin in childhood 
 on the occasion of a firs!, infectious di ea e or imple digestive di - 
 turbances the importance of which is jusl being appreciated. The 
 numerous fermentations which 80 easily occur in nun lingE produce 
 alterations in the entire organism, and may evidently become the 
 starting point of a number of organic affections the origin of which 
 often remains undiscovered. I! is conceivable, however, that 
 scleroses become more frequenl as the individual advance- in wi<-. 
 The aged are almost always affected by it. It is quite difficult, 
 however, to determine the part due to the infection. Visceral or 
 arterial scleroses are the termination of all pathogenic causes which 
 have acted upon the organism and which are almosi always multiple. 
 Exogenic intoxications (alcoholism, saturnism) and endogenic intox- 
 ications (autointoxications) are superadded to infectious intoxi- 
 cations and give rise to alterations which end in sclerosis. The 
 organic lesion thus constituted preserves no character of its origin. 
 On the contrary, it acquires a perfect autonomy, progresses on its 
 own account, and in its turn engenders disorders which are always 
 the same regardless of their point of departure. This is the reason 
 why physicians have long believed in the existence of diseases of the 
 organs when in reality they were nothing more than organic affec- 
 tions, more or less tardy consequences of previous diseases. 
 
 It is thus intelligible that the histor}' of the consequences of 
 infections may be at times of greater importance than the history 
 of the infections themselves. Anything that is known as diseases 
 of organs may be the tardy consequence of an infectious process. 
 The reason visceropathies are not more serious and frequent is that 
 the means of defense and of compensation at the disposal of the 
 organism are extremely numerous. 
 
 If we consider in their entirety the modifications produced by 
 infection in organs and tissues we see that it is possible to classify 
 them under three headings : modifications expressing increased func- 
 tional activitj'; modifications in the structure of the cellular elements 
 and modifications in texture — i. c, changes in their mutual ordi- 
 nation. 
 
 Increased functional activity represents a return of the organism 
 to a former state of its evolution. It is a kind of rejuvenation which 
 
550 ISFECTIOUS DISEASES. 
 
 is particularly appreciable in the bone-marrow, but which is no less 
 manifest when chemical anatysis is applied to other tissues. Infec- 
 tion thus arouses functions which seem to be extinct. But this 
 favorable occurrence is calculated to remedy immediate accidents 
 only. By adding the favorable and unfavorable effects, we find that 
 the latter exceed. This conclusion suggests a practical consequence. 
 Infection being so dangerous, even when slight, not so much on its 
 own account as by reason of its remote consequences, we must be 
 extremely circumspect in matters of bacteriotherapy. Even when 
 no immediate disturbance becomes manifest we may ahvays suspect 
 that the injection of attenuated microbes or of toxins may be the 
 cause of some tardy lesions. This remark is applicable to bacterio- 
 therapy procedures as well as to vaccinations. We shall again refer 
 to this method in treating of the effects of vaccinations. 
 
CH A PTEB X I X. 
 MECHANISM OF [MMUNITY AND OF PREDISPOSITION. 
 
 Importance of Physical and Chemical Modification oi thi Organi m Germicidal Prop- 
 erties of the Fluids. History, Natural Immunity. Action of the Serum of Normal 
 Animals upon the Development, Morphology, and Virulence of Microbe Germi- 
 
 cidal Actii f tin- Serum of Vaccinated Animal Action of the Serum upon the 
 
 Morphology of Microbes. Agglutinating Power. Attenuating Power of ii" Serum. 
 Antitoxic Properties. Passage of Active Substance into the Secretion Germi- 
 cidal Properties of the Tissues. Modification of the Serum in Animal Predi | 
 
 to Infections. Modifications of the Scrum in the < Im- 
 
 portance and Significance of Modification*- in tic fluid- Nature and Origin of 
 
 Different Active Substances Contained in Serum- Conclu •••■ding the 
 
 Mechanism of Immunity. 
 
 The numerous researches pursued upon the interesting subject 
 of the mechanism and predisposition of immunity have considerably 
 
 elucidated certain points of this important question of general 
 pathology. The results, however, have been so unexpected or so 
 
 contradictory as to give rise to spirited controversies. The question, 
 perhaps, appears to be more obscure than it really is, for the reason 
 that a simple formula has been sought to explain complex facts. 
 
 Immunity is the result of multiple conditions. Therefore, ex- 
 clusive theories are necessarily insufficient. Unfortunately the 
 investigation of causes which explain the resistance to infections is 
 surrounded by great difficulties, and the explanation of experimental 
 results is but seldom satisfactory. 
 
 Everyone is acquainted with the famous experiment of Pasteur, 
 who subjected a chicken to cold by plunging it into water. The 
 chicken, which was until then refractory to anthrax, became sus- 
 ceptible to the disease. The conclusion that the chicken has an 
 organic temperature too high to favor the development of the 
 bacillus anthrads seems evident. When this temperature is lowered 
 immunity is abolished. The same explanation holds good with an 
 inverse experiment. A frog is immune from anthrax infection 
 because its temperature is too low. When this animal is heated. 
 as was done by Gibier, it contracts the infection. These experi- 
 ments appear to be very simple and easy of explanation. In reality, 
 however, the facts are highly complex. When we modify the 
 
552 IXFECTIO US DISEASES. 
 
 organic temperature of an animal we create a whole series of dis- 
 turbances. We change the chemical state of the fluids and tissues; 
 we completely transform the sensibility of the nervous system, the 
 activity of the circulation, respiration, and nutritive exchanges. 
 We thus cause an incalculable number of modifications, and do not 
 know which play the most important role in the final result. The 
 fact that the pigeon, the temperature of w T hich is about the same 
 as that of the chicken, quite easily contracts anthrax infection, 
 proves that the high temperature of the chicken is not the cause 
 of its immunity. On the other hand, the resistance of the frog- 
 does not depend upon its low temperature, since, at least during 
 summer, the bacillus anthracis readily develops at the surrounding 
 temperature, and the toad, the temperature of which is near that 
 of the frog, does not enjoy the same immunity. Finally, we have 
 made the following experiments which seem to us conclusive: 
 Frogs were placed in an incubator for two days. They were then 
 immersed in cold water and inoculated with anthrax. Several of 
 them succumbed to the infection, although their temperature had 
 fallen to its normal degree. It is, therefore, certain that by varying 
 the surrounding temperature we act upon the entire organism; we 
 modify its sensitiveness to living microbes and toxins, just as we 
 modify, under similar conditions, its sensitiveness and its resistance 
 to vegetable alkaloids. In the latter instance there is no question 
 of favoring or hindering the development of the pathogenic agent. 
 The result evidently depends upon dynamic modifications of the 
 organism. 
 
 The cause of resistance and of predisposition must, therefore, be 
 sought for in the changes presented by living beings. Numerous 
 experiments . pursued in recent years have shed light upon these 
 modifications of the organism. According to some authorities 
 immunity is due to a chemical state of the fluids and tissues — a 
 chemical state hindering the development of bacteria, disturbing 
 their functions, diminishing their virulence, and neutralizing their 
 toxins. This is the germicidal or antitoxic theory. According to 
 others, immunity depends upon a dynamic state of the cells which 
 are supposedly capable of destroying the microbes. This is the 
 vital theory, the phagocytic theory. These theories have long been 
 and are still being discussed. I have always contended that no 
 exclusive opinion should be held regarding these questions. 
 
 Predisposition and immunity are complex properties ; they are due 
 
MECHANISM OF IMMUNITY AND OF PREDISPOSITION 
 
 to multiple factors, some of which are ju I becoming known. It 
 is evident from facts hitherto observed thai immunity 
 as predisposition cannot be explained by an exclu ive doctrine. 
 In other words, it seems to me u elet to oppo e th< greal 
 
 theories to each oilier. I! is better to endeavor to harmonize them 
 and to elucidate the relations existing between them. I hope to 
 succeed in showing thai the muds play an importanl rdle by weaken- 
 ing the pathogenic germs and by diminishing their resistance. They 
 thus favor phagocytosis. On the other hand, the fluids being pro- 
 ducts of the cells, all modifications in ih»' organic fluid* require a 
 previous modification in the figurate elements. Here is a aewpoinl 
 of contact between the so-called humoral and cellular doctrines 
 which, at first sight, appear so much a1 variance. 
 
 Action of Fluids upon Bacteria. 
 
 History. If a certain amount of a culture is injected into the 
 
 veins of an animal and then blood drawn several limes from the 
 animal, and microbes looked for, it is seen that the number of microbes 
 rapidly diminishes. At the end of a few hours the blood becomes 
 sterile. The microbes accumulate in the organs in which they 
 vegetate and from which they again invade the blood during the 
 last moments of life. This interesting result, pointed out by Fodor 1 
 and by Wyssokowitsch, 2 was confirmed by a great number of experi- 
 menters, and at present seems to be indisputable. By what mechan- 
 ism does the blood free itself of the parasites introduced into the 
 circulation? In a thesis written under the inspiration of Prof. 
 Schmidt and defended in Dorpat in 1884, Grohmann established 
 that the blood modifies the vitality of microbes sown in it. The 
 anthrax bacillus particularly becomes thus attenuated to the point 
 of being incapable of killing a rabbit. The question was taken up 
 by Fodor. By introducing the bacillus anthracis into the blood 
 drawn from a rabbit immediately after it was killed, this author 
 found that the number of the bacteria progressively diminished. 
 Subsequently, after a variable lapse of time, a few microbes which 
 had escaped the destructive action of the blood, finally got the upper 
 
 1 Fodor. Die Fahigkeit des Blutes Bacterien zu vernichten. Deutsche med. Wochen- 
 schrift, 1SS7. 
 
 2 Wyssokowitsch. Ueber das Schicksal der in's Blut injicirten Mikroorganismen. 
 Zeitschrift f. Hygiene, 1887. 
 
554 IXFECTIO US DISEASES. 
 
 hand and succeeded in developing. The works of Fliigge 1 and his 
 disciples, Nuttal and Nissen, however, drew attention to this highly 
 important question. Their researches showed that various microbes 
 when sown in the blood undergo therein at first a degeneration 
 clearly appreciable by microscopic examination. A great many of 
 the bacteria are destroyed, while others persist and may again 
 vegetate at the end of a variable period of time. 
 
 The researches above cited, notwithstanding their undoubted 
 interest, are open to some objections. It was remarked that the 
 resistance of an animal is not always related to the germicidal power 
 of its blood. Thus, Nuttal noted that the blood of the rabbit 
 exerted upon the anthrax bacillus a more marked destructive action 
 than did the blood of the dog. There is yet a graver criticism to be 
 made. The blood employed for the cultures contained figurate 
 elements : hence it was possible that the destruction of the microbes 
 w^as partly accomplished by the blood cells. Although the majority 
 of the degenerated bacteria were found outside the leucocytes, it 
 might, nevertheless, be supposed that the modification was due to 
 some soluble substance derived from these elements. By heating 
 the blood between 122° and 131° F. (50° and 55° C), we see that it 
 loses its germicidal action, a fact which may be due to the death 
 of the figurate elements as well as to chemical modification. A very 
 ingenious experiment of Petruschky, however, seemed to demon- 
 strate that the germicidal action of the fluids is real. By introducing 
 beneath the skin of frogs virulent bacteria, and by protecting them 
 against the phagocytes by means of a parchment membrane, this 
 author found that the microbes were attenuated and destroyed. 
 There is, therefore, no escape from admitting the action of the 
 interstitial fluids which alone had been able to diffuse. The experi- 
 ments, however, which dissipated all doubt are due to Behring 2 and 
 Buchner. These authors operated not only with total blood, but 
 also with serum, namely, with a fluid deprived of cells, and demon- 
 strated that this fluid possesses notable germicidal properties. 
 Buchner further recognized that these properties diminish or disap- 
 pear when the serum is heated for an hour at a temperature of 131° F. 
 (55° C), or when its nutritive pow r er is increased by the addition of 
 
 1 Fliigge. Studien iiber Abschwachung virulenter Bacterien unci die erworbene 
 Immunitat. Zeitsehrift f. Hygiene, 1888. 
 
 2 Behring. Ueber die Ursache des Immunitat von Ratten gegen Milzbrand. Central- 
 blatt f. klinische Medicin, 1888. 
 
MECHANISM OF IMMUNITY AND OF PREDISPOSITION 
 
 peptones, or by submitting the total blood to a erie ol con- 
 gelations and meltings, operations which de troy the red blood 
 corpuscles and liberate their contents. 
 
 Stimulated by these works, a great numbei oi i Kperimentei took 
 up the study of the germicidal power of normal blood. It will suffice 
 to cite the names of Fodor, Buchner, Behring, Karlinski, Stern, 
 Bankin, Ogata, Jasuhara, Sanarelli, Phi alix, Gioxa, and Guarnieri. 
 While, however, numerous facts demonstrated thai under normal 
 conditions the serum possesses germicidal propertie . are the latter 
 increased in vaccinated animals? The majority of authors who 
 first attempted to solve this question answered negatively. They 
 took ground on the fad thai microbes develop in bouillon prepared 
 with the tissues of refractory animals. While, on the one hand, 
 Schottelius noticed that the bacillus of swine erysipelas vegetates 
 with difficulty in culture media prepared with the muscles of ani- 
 mals which have died of this affection, on ihe other hand, Bitter 
 reached an entirely different result. In all eases, however, the 
 tissues were submitted to some alteration, and we know at present 
 that heating destroys the germicidal properties of albuminoid .-lib- 
 stances. 
 
 In order to realize a conclusive experiment, it was necessary to 
 study comparatively the development of microbes in the fluid- of 
 normal and of vaccinated animals. A first endeavor in this direction 
 is that of Metchnikoff, 1 who found that the anthrax bacillus was 
 attenuated in the blood of vaccinated sheep; but he experimented 
 with total blood, that is, blood containing figurate elements, and he 
 attributed the effect which he observed to the action of the latter. 
 Sometime later, Gamaleia showed that during the anthrax fever 
 and the fourteen days following it the aqueous humor is modified. 
 If the anthrax bacillus is sown therein the microbe develops under 
 a new form and loses part of its virulence. According to this author. 
 however, this germicidal state is transitory; it disappears while 
 immunity persists. 
 
 We then took up the study of the question and cultivated com- 
 paratively microbes on the serum of non-vaccinated animals and oi 
 animals vaccinated either against the bacillus pyocyaneus, 8 or the 
 
 1 Metchnikoff. Sur 1 'attenuation ties bacteridies charbonneuses. Annates de l'Institut 
 
 Pasteur, 1SS7. 
 
 2 Charrin et Roger. Note sur le developpement des microbes pathogenes dans le 
 serum des animaux vaccines. Soci&te' de biologic. 1889. 
 
556 INFECTIOUS DISEASES. 
 
 bacillus of symptomatic anthrax. 1 In both instances we observed 
 that, as a result of vaccination, the serum became a bad culture 
 medium for the microbe against which the animal was protected. 
 These results were soon afterward confirmed hy Behring and Nissen. 2 
 
 The serum of vaccinated animals acts, however, not only upon the 
 numerical development of microbes, but is capable also of modifying 
 the forms of bacteria which resist and finally succeed in multiplying. 
 It exerts upon them an agglutinating action, modifies their functions, 
 and finally, as I have demonstrated with regard to the streptococcus, 3 
 it diminishes their virulence. All these influences are unfavorable 
 to the microbe and may be united, as was proposed by Bouchard, 
 under the general name of germicidal properties. The expression 
 is not taken in its strict etymologic sense f it may only be opposed 
 to that of antitoxic property, which is applied to the discovery of 
 Behring and Kitasato. 5 As is known, these authors demonstrated 
 that the organism secretes antitoxins capable of suppressing or 
 neutralizing the action of toxins. The antitoxic power, whether 
 exercised upon the toxin, bj?- destroying it, or, what is more likely, 
 upon the economy by increasing its resistance, completes the germ- 
 icidal power in the defense of the organism. 
 
 Here, therefore, are a series of facts showing that vaccination 
 produces in the organism a number of chemical modifications which 
 must play an important role in its resistance. But a new question 
 has been raised by the study of morbid predispositions. Are the 
 germicidal properties of the fluids diminished in an animal in which 
 the resistance to the virus is diminished? The experiments which 
 we have pursued upon this subject and those published by Bakunin 
 and Boccardi, Bastin, and Montuori enable us to answer in the 
 affirmative. Thus, it may be stated that the germicidal properties 
 of the blood vary with the receptivity of the animals. They increase 
 
 1 Roger. Nouvelles recherches sur les propri6tes microbicides du serum. Ibid., 1S90. 
 Contribution a l'dtude experimental du charbon symptomatique . Revue de medecine, 
 1891. 
 
 2 Behring and Nissen. Ueber bakterienfiendliche Eigenschaften verschiedener Blut- 
 serumarten. Ein Beitrag zur Immunitatsfrage. Zeitschrift f. Hygiene, 1890. 
 
 3 Roger. Modification du serum a la suite de Perysipele. Societe de biologie, 1890. 
 R61e du semm dans l'attenuation des virus. Revue generate des sciences, 1891. Le 
 pouvoir att6nuant du s6rum. La presse m6dicale, March 4, 1896. 
 
 4 [Antimicrobic would be a more comprehensive expression than germicidal. Trans- 
 later.] 
 
 6 Behring and Kitasato. Ueber das Zustandekommen der Diphterie-Immunitat und 
 der Tetanus-Immunitat. Deutsche med. Wochenschrift, 1890. 
 
MECHANISM OF immunity AND OF PREDISPOSITION. :,:,] 
 
 when the resistance of fche animals i fcrengthened, and via ver a. 
 This clearly shows the interesl of the presenl tudy. 
 
 Natural Immunity, [f the germicidal properties of the organic 
 fluids play a real role in the mechanism of immunity they musl be 
 
 i.Ik; more iniirkcd i he more icsistanl the animal. Authors who have 
 studied ii:il,nr;il iiiiinunity have a1 i i 1 1 1 < ■ observed result* contrary 
 to what would logically be anticipated. Nuttal, for example, 
 noticed that the serum of the rabbil exerts a more marked destructive 
 action upon the anthrax bacillus than docs the serum of the dog. 
 Hero is an absolutely misleading fact. Is it not known thai the 
 dog, although liable to contrad anthrax infection, is more resistanl 
 than the rabbit? The experiment just noted was of too greal conse- 
 quence to be left uncontrolled. We, therefore, took up the question 
 and found the fact to be perfectly exact. This strange fad ifi true 
 not only of anthrax, but also of symptomatic anthrax. The rabbil 
 is naturally immune from this infection, and the guinea-pig i- very 
 sensitive to it; and yet the serum of the guinea-pig is far more 
 germicidal than that of the rabbit. Experimentation has demon- 
 strated this fact, and the conclusions which may be deduced there- 
 from deserve to be discussed. 
 
 Action of Serum upon the Morphology of Microbes. It does not 
 suffice to study the numerical development of microbes. It is also 
 necessary to investigate what becomes of their properties and estab- 
 lish whether their development is effected according to the normal 
 type. It has already been stated that the morphology of the 
 bacillus anthracis varies with the serum in which it develops. In 
 the guinea-pig we find delicate regularly segmented filaments as in 
 bouillon. In the rabbit we find rods either isolated or united in 
 pairs. In the frog, long chains appear which are very slender and 
 segmented at variable intervals. These first facts, which were con- 
 firmed and completed by Pane. Pernisse, and Alessi, demonstrated 
 that the development of the anthrax bacillus does not take place in 
 a normal manner. But it was of greater importance to determine 
 the variations of virulence under these different conditions. 
 
 Action of Serum upon Virulence. Ogata and Jasuhara have con- 
 tended that the anthrax bacillus when sown in the blood or the 
 serum of the frog, dog, or white rat loses its virulence. If. after two 
 or three days, it is inoculated into a mouse the animal resists. The 
 antiseptic power of the blood of the frog is so marked that one drop 
 suffices to confer immunity upon a mouse. The blood of the dog 
 
558 ISFECTIOUS DISEASES. 
 
 and of the white rat act similarly, provided it is employed in a 
 larger dose. The blood of a calf, which is a non-refractory animal, 
 remains without effect. Sanarelli, experimenting with the serum of 
 frogs freed of the leucocytes, likewise noticed that the bacillus was 
 attenuated in this medium within three or four days if it was sporu- 
 lated, and more rapidly if it was asporogenic. 
 
 Unfortunately, all these results have been contradicted. Enderlen, 
 Petermann, and Roudenko experimented with the blood of dogs or 
 frogs and obtained no attenuation. The action of the serum is 
 well demonstrated only in the case of the white rat. The question 
 seems to be one of noxious effects exerted upon the microbe itself, 
 since the researches of Metchnikoff and Roux appear to show that it 
 is necessary to place the serum and spores in contact in order to 
 annihilate the pathogenic action of the latter. 
 
 On the other hand, it is not sufficient to study the chemism of the 
 blood. The action of the organs must also be investigated. As the 
 microbes retire from the blood current into the viscera and tissues, 
 in order again to invade the blood at the end of life, we must study 
 the modifications which these microbes undergo in the depths of 
 the economy. Few researches have been pursued in this direction, 
 and those that have been undertaken with another end by Phisalix, 
 for example, tend precisely to demonstrate that microbes find in 
 certain tissues favorable conditions which enable them to resist 
 the germicidal action of the blood. This result accounts for the 
 apparent contraction between the high germicidal power of the fluids 
 and the absence of natural immunity. Moreover, in discussing 
 these researches, the fact that the organism is not an inert medium 
 seems hardly ever to have been considered. In fact, the organism 
 reacts from the very start of the infection, at the same time that it 
 is subjected to the action of microbic toxins. Hence, two orders of 
 modifications take place. Some are due to the action of the microbes, 
 and probably reduce the means of defense; others depend upon 
 organic reactions and strengthen these means of defense. 
 
 In conclusion we would like to say that, in order to investigate in 
 a useful manner the problem of natural immunity, we should pene- 
 trate as completely as possible the mechanism of infection and keep 
 constantly in mind that the various modes of defense have only a 
 relative and not an absolute value. 
 
MECHANISM OF IMMUNITY AND OF PREDI8POSITI0 
 Acquired Immunity. 
 
 Germicidal Action of the Serum of Vaccinated Animal.s. A hi already 
 
 been stated, after the results of Nuttal, which were nol perfectly 
 demonstrative, we undertook the study of the modification* in the 
 serum of vaccinated animals. Our firsl investigations, pursued 
 with Dr. Charrin, 1 were made upon the bacillus pyocyaneus. Blood 
 taken from normal and from vaccinated animals was kepi for twenty- 
 four hours, when the scrum was separated and pul in tubes, 3 cubic 
 centimetres in each. A very small dose, 0.02 c.c. or 0.002 c. c. of 
 pyocyaneus culture, prepared in bouillon, was then introduced into 
 the tubes, wliieli were shaken and subjected to study. Some experi- 
 menters thought thai the germicidal action of the -<Tum under these 
 conditions depended simply upon the facl thai the culture made in 
 bouillon was transferred to a different medium — i. e., the serum. 
 We therefore often took our virus from cultures made in normal 
 liquid serum. The results were identical in both instances. In fact, 
 on the following day it was possible to clearly see with the naked eye 
 notable differences in the mode and intensity of vegetation of the 
 microbe, according as the culture was made in normal serum or in 
 serum obtained from vaccinated animals. The normal serum was 
 completely opaque, turbid, and of a bluish-green color. It contained 
 a few flocculi which increased in number on the following day.-. < >n 
 the other hand, the serum of the vaccinated animals became but 
 very slightly turbid. The bacilli were united in small masses float- 
 ing in the fluid. On the following days the development was more 
 noticeable, and the differences, although appreciable, were Less 
 striking. 
 
 When, however, the animal is well vaccinated, the cultures made in 
 its serum always preserve a peculiar appearance. The fluid remains 
 clear, and the microbes are united in small masses which are scat- 
 tered when the tube is shaken. Moreover, while the bacillus gives 
 a fine blue color in normal serum, it produces no pigment in the 
 serum obtained from vaccinated animals; the culture medium 
 assumes a dirty brown hue. 
 
 These first results led the author to study other infections from this 
 point of view, and he experimented with the bacillus of symptomatic 
 
 1 Charrin and Roger. Note snr le developpement des microbe? pathogdnes dans le 
 serum des animaux vaccines. Soc. de biologic. 1SS9. 
 
560 IXFECTIO US DISEASES. 
 
 anthrax. 1 Guinea-pigs were either vaccinated with the virus atten- 
 uated according to the method of Arloing, Cornevin, and Thomas, 
 or inoculated with small amounts of virulent fluid beneath the skin 
 of the ear. Four or five days after the last preventive inoculation, in 
 order to ascertain their resistance, a few drops of symptomatic an- 
 thrax serous exudate mixed with lactic acid were injected into the 
 animals. Those guinea-pigs which resisted were bled after a period 
 varying from eight to twenty-two days after the test inoculation, and 
 their serum was inoculated comparatively with the serum of normal 
 guinea-pigs. The smaller amounts inoculated the more marked were 
 the differences in development. Thus, when 0.08 c.c. to 0.1 c.c. 
 of sj'mptomatic anthrax serous exudate were mixed with 3 c.c. of 
 serum, it was noticed on the following day that growth had begun 
 in all the tubes, but was less pronounced in the serum obtained from 
 the vaccinated animals. On the second day the differences were 
 far more appreciable. Even the macroscopic appearance showed 
 that development was far more luxuriant in the normal serum, which 
 was completely opaque, and microscopic examination revealed 
 therein a far greater number of bacilli. 
 
 A short time after our first investigations the contributions of 
 Behring, Nissen, and Zasslein appeared, which contributed additional 
 facts to those observed by us. Behring and Nissen established that 
 vaccination of the guinea-pig against MetchnikofFs vibrio imparts 
 to the serum of this animal a germicidal power which is absent in 
 the normal state. 
 
 Action of the Serum upon Morphology. The modifications pre- 
 sented in the morphology of the bacillus anthracis have already been 
 referred to in connection with normal serum. The influence of the 
 serum of vaccinated animals is still more definite. Let us take, for 
 example, the cultures of the bacillus pyocyaneus. The microbes 
 developing in normal serum present nothing special. They are 
 small rods analogous to those observed in artificial culture media 
 habitually employed in bacteriology. The appearance is altogether 
 different in the serum of refractory animals. In the latter instance 
 the microbes are united in chains of variable length made up of six 
 to ten segments. The length of these strepto-bacilli is less than that 
 of the normal bacilli. The size of the segments varies; some of 
 
 1 Roger. Nouvelles recherches sur les propridtes microbioides du serum. Societd de 
 biologie, 1890. Contribution a l'dtude experimentale du charbon symptomatique. 
 Revue de mddecine, 1891. 
 
MECHANISM OF IMMUNITY AND OF PREDISPOSITION. :,<;] 
 
 fchem are extremely short, being half a Large a a normal bacillus; 
 many attain, and a few exceed, the normal length. In general, .'ill 
 the segments of the same chain are nearly of the same dimensions. 
 Some diplo-bacilli and a few isolated one are al o ob erved. The 
 protoplasm of these dements does no1 tain a well a in the normal 
 state, and not infrequently lome clear patche are found. Finally, 
 these elements manifesl a remarkable inclination to form groups, 
 and, instead of swiniming freely like normal bacilli, they are found 
 in small masses, which accounts for the clotted appearance of the 
 cultures. The differences observed with symptomatic anthrax are 
 no less marked from this point of view. 
 
 Agglutinating Power of Serum. Cultures made in the blood of 
 
 vaccinated animals presenl a peculiar appearance due to the delay 
 of development or to modifications imposed upon certain functions. 
 At the same time, however, an agglomeration of the figurate element* 
 may be observed, which imparts to the culture medium a clotted 
 appearance which is altogether characteristic. In studying with 
 Dr. Charrin the development of the bacillus pyocyaneus in the serum 
 of vaccinated rabbits we first observed the agglutinating power of 
 serums. We noted that the microbes, often united in chains, 
 manifested a strong tendency to form groups, and, instead of freely 
 swimming like normal bacilli, they formed small masses. This fact 
 explains the appearance of the cultures. In fact, these remain clear 
 and transparent ; the microbes fall to the bottom of the tube, where 
 they unite in clots. 1 Dr. Metchnikoff 2 made similar observations 
 with the avicide vibrio, then with the microbe of pneumonia; but 
 lie later recognized that this agglutinating property does not belong 
 to the sera of all vaccinated animals. It is lacking, for instance. 
 in animals immunized against the bacillus of hog cholera. Gruber 3 
 took up the question and completely modified the method. He 
 introduced a new and very simple procedure for determining whether 
 or not a given serum was derived from a vaccinated animal. He 
 took a small amount of culture and mixed it with serum upon a slide. 
 When the serum was derived from a normal animal the microbes 
 remained disseminated; when it was obtained from a vaccinated 
 
 1 Charrin and Roger. Xote sur le developpement des microbes pathog&ies dans le 
 serum des animaux vaccines. See. de biologic Nov. 23, 1SS9. 
 
 2 Metchnikoff. Etudes sur l'immunite (4th memoire). Annates de ITnstitut Pasteur, 
 1891, pp. 473, 474. Etudes sur l'immunite (,5th memoireV Ibid.. 1892, p. 29-i. 
 
 3 Gruber. Theorie der aktiven und passiven ImmunitaT gegen Cholera. Typhus, und 
 Verwandte Krankheitprozesse. Munchener med. Wbchensehrift, 1896, p. - 
 
 36 
 
562 INFECTIOUS DISEASES. 
 
 animal the microbes agglomerated and agglutinated. Gruber ob- 
 served this result with the microbes of cholera and typhoid fever 
 and noticed that The phenomenon is clearer the more intensely the 
 animal is immunized. From this time on innumerable contributions 
 appeared upon the question of agglutination. The chief results 
 obtained may be given in resume in the following conclusions: 
 
 The agglutinating power often exists in the serum of normal 
 animals. Horse serum agglutinates the cholera vibrio, the colon 
 bacillus, and the tj^phoid bacillus. Likewise the sera of most 
 animals agglutinate the bacilli introduced by the first inoculation 
 of anthrax, independently of any relationship between the intensity 
 of agglutination and the immunity of the animal. Thus, according 
 to Gengou, the serum of the rat agglutinates in a dilution of 1 : 10, 
 the serum of the guinea-pig in 1 : 20, that of the dog in 1 : 100, 
 and that of man in 1:500. Man is far more sensitive to anthrax 
 than the rat, and yet his serum is fifty times more active. The 
 serum of the guinea-pig and that of the dog have an almost equal 
 agglutinating power, while the resistance of these animals is quite 
 different. 
 
 The agglutinating power appears not only in vaccinated animals, 
 but also in the course of infections, and this propert}', which is 
 acquired also by the blood, has been turned to profit by Widal for 
 diagnostic purposes. As a rule, the better the individual resists a 
 disease the earlier the agglutinating power appears and the more 
 energetic is its action. The serum prognosis of P. Courmont is 
 based upon this fact. 
 
 The serum acquires agglutinating properties not only with respect 
 to bacteria, but also as regards more highly organized plants, as we 
 have shown to be the case, for instance, with the fungus of aphtha 
 (Figs. 11 and 12, pp. 311, 312). Finally, cellular elements, such as 
 red blood corpuscles, and organic substances, such as casein, may 
 be agglutinated as well as microbes. Animals which have received 
 blood drawn from various species yield a serum agglutinating the 
 red blood corpuscles of the blood which has been injected into them. 
 The result is identical when milk is employed. 
 
 The agglutinating reaction is specific. It is exercised only upon 
 the element against which the animal reacts. This fact may serve 
 to differentiate microbic species and even simple varieties. 
 
 Attenuating Power of Serum. We have already stated that cer- 
 tain streptococci develop as readily in the serum of normal as in 
 
MECHANISM OF IMMUNITY AND OF PBEDISPOSITIOH .,<;.; 
 
 that of vaccinated animals, in pursuing our research! 
 ni/(!(l that I. he numerical development was the same, while the 
 pathogenic, properties, were quite different. Take, for in tance 
 cultures twenty four hours old, one prepared in normal serum, the 
 other in that of a vaccinated animal. It' the ame amount of each of 
 these cultures is injected beneath the skin of the ear of two rabbits, 
 the results are round to be quite different. In some instance 
 culture prepared in normal serum proves highly virulent, and if a 
 large dose, say sixteen drops, is introduced, the animal diet within 
 two or three days. The local lesion is slight; a general infection 
 takes place, as may be proved by cultivation from the viscera. The 
 cultures prepared in the serum of the vaccinated animal, under the 
 same conditions as in the preceding, give rise to a local lesion, a 
 more or less extensive erysipelas; but the general state remains 
 good and the animal rapidly recovers. 
 
 The streptococci thus acquire different properties according 
 they are developed in the serum of normal or of vaccinated animals. 
 In both instances vegetation is similar, but the microbes derived 
 from the serum of the vaccinated animal lose much of their virulence 
 and become attenuated. This is an important fact from the stand- 
 point of general pathology. 
 
 It is to be noted, however, that the agents which develop in the 
 serum of animals rendered refractory do not lose all of their patho- 
 genic power: there is a reduction but not abolition of virulence. 
 This is not to be wondered at, since vaccinated animals develop a 
 local lesion when active microbes are inoculated into them. 
 
 These remarks are applicable also to the pneumococcus, which 
 likewise becomes attenuated in the serum of refractory animals. 1 
 This result was confirmed by Arkharow. 2 The researches of this 
 author were strongly criticised by Metchnikoff, in whose laboratory 
 the investigations were pursued. Therefore, we shall not dwell upon 
 them. We must mention, however, a very curious fact discovered 
 by Mosn} r . According to this experimenter the pneumococcus lives 
 longer in the serum of a vaccinated than in that of a normal rabbit. 
 This fact has nothing paradoxical about it. Dr. Mosny himself 
 remarks that the microbe is, so to speak, in a state of latent life in 
 
 1 Roger. Role du s<5rum dans l'attenuation des virus. Revue generale des sciences, 
 June 30, 1891. 
 
 2 Arkharow. Gu6rison de l'infection pneumonique chez les lapins. Archives de 
 medecine exper.. July. 1892. 
 
564 INFECTIOUS DISEASES. 
 
 the serum of the vaccinated animal. While the microbe does not 
 die, it does not develop. It behaves as in an unfavorable medium. 
 It does not secrete the substances which arrest its own vegetation. 
 
 The attenuating action of serum was further demonstrated by the 
 experiments of Dr. Courmont. This scientist cultivated the staphy- 
 lococcus aureus in comparative series in the sera of vaccinated and 
 of normal animals. After several successive passages in the two 
 media he transferred the microbes to bouillon, and these last 
 cultures he employed for inoculation. In this manner he avoided 
 introducing therapeutic serum. The virulence was preserved intact 
 in the normal serum, while it was reduced or destroyed in the sera 
 obtained from animals which had been rendered refractory. 1 Anal- 
 ogous researches pursued by Nicolas 2 proved this conclusion to be 
 applicable to the bacillus of diphtheria. We might also cite the 
 experiments of Denys and Leclef with streptococci and those of 
 Babes, Sternberg, Beclere, Chambon, and Menard, demonstrating 
 that the virus of hydrophobia and that of vaccinia lose their prop- 
 erties in contact with the sera of refractory animals. 
 
 Antitoxic Properties of Serums. As microbes act mostly by the 
 toxic substances which they secrete, it was natural to investigate 
 the action of serum upon microbic products. We owe to Behring 
 and Kitasato the first experiments upon this question, experiments 
 which oppened a new route for therapeutics. These facts are at 
 present too well known to require long discussion in this place. 
 The serum of an animal vaccinated against diphtheria has but very 
 slight germicidal power (Nicolas), but it possesses the far more 
 important property of neutralizing the diphtheritic toxin. The 
 antitoxic power of the serum is so marked that a guinea-pig weighing 
 400 grams is preserved against a fatal dose of toxin by 0.008 c.c. 
 of serum. In other words, 1 c.c. of serum preserves 50,000 grams 
 of living matter. Such is the strength of the serum furnished by 
 the Pasteur Institute. 
 
 Tetanus is comparable to diphtheria in that the microbe remains 
 localized at one point of the organism and acts only by its toxins. 
 Its mode of attack and the mode of defense of the economy are 
 similar to what occurs in diphtheria. The serum of animals vaccin- 
 
 1 Courmont. Sur les propri6tes bactericides ou microbiophiles du s6rum du lapin, 
 suivant que cet animale est vaccine contre le staphylocoque pyogene ou predispose a 
 cette infection. Archives de physiologie, January, 1895. 
 
 2 Nicolas. Pouvoir bactericide du se>um antidiphterique. These de Lyon, 1895. 
 
MKdllANlKM of IMMUNITY AND OF PREDIBP08ITI0N, 
 
 ated against tetanus is also an .'niiiiM.--.ic serum. Behring and 
 Kitasato, to whom also this discovery is due, affirm thai thfc serum, 
 when injected into animals, pre erve them from tetanu . and may 
 even cure the established disease. They s serl thai il u possible 
 to save a mouse which already manifests the characteristic con- 
 tractures. These experiments, however, repeated by Tizzoni and 
 ( -attain, Vailla.nl, and again by Kitasato himself, gave negative 
 results from a therapeutic standpoint. Soon after Roux and Vail- 
 la.nl 1 showed that the serum injected before inoculation | 
 the animals. When introduced simultaneously with the toxin-, or 
 a little after, if diminishes the intensity of the symptoms and permits 
 the development of only ,a local tetanus, [1 is ab olutery ineffectual 
 when injected info animals already presenting contractus 
 
 In a great number of infections it may, perhaps, !><• possible to 
 prepare, by certain experimental contrivances, cither germicidal or 
 antitoxic sera. To this end the method- of vaccination may lie 
 varied. This has been accomplished by researches pursued with 
 regard to cholera and typhoid fever. Pfeiffer obtained a germicidal 
 serum against the vibrio of cholera. The animals which furnished 
 this fluid received vibrios killed by means of chloroform fumes and 
 heat and increasing doses of living vibrios. The serum acted 
 against the disease produced by intraperitoneal inoculation of 
 cholera bacilli, but it failed when it was tried upon animals inoculated 
 through the intestine. Even in cases of peritonitis the serum acts 
 only when it is injected a short time after inoculation and when the 
 dose of virus introduced is not too large. Pfeiffer , who has made 
 a thorough study of this question, has shown that the serum should 
 be injected half an hour after inoculation in order to succeed. It is 
 inert if it is employed after an hour and a half. The same author 
 established that y ¥ of a milligram of serum suffices to neutralize 
 2 milligrams of culture, but he recognized that even a considerable 
 amount of serum does not protect against intraperitoneal injection 
 if the dose of the culture is greater than one platinum loopful per 
 100 grams of weight of animal. The fact is that when the culture 
 is introduced at the end of a certain time or in too large amount, not 
 only the microbes introduced, but also the toxins elaborated within 
 the organism or contained in the culture must be taken into account. 
 The serum is only germicidal, it weakens and kills the figurate 
 
 1 Roux and Vaillard. Contribution a l'etude du tetanos. Annates de l'Institut 
 
 Pasteur. February. 1S93. p. 65. 
 
566 I - v FECTIO US DISEASES. 
 
 elements; it is not antitoxic, namely, it exerts no action upon the 
 poison of cholera. As a matter of fact, Pfeift'er, Wassermann and 
 Metchnikoff have noted that vaccinated animals which are refractory 
 to virulent inoculation arc as sensitive to the influence of toxins as 
 normal animals, or even more sensitive 
 
 These results explain why Pfeiffer's methods do not succeed much 
 with man. In the case of spontaneous disease the question is one 
 of intoxication rather than of infection. The microbe multiplies in 
 the intestine, but it is the toxins absorbed therefrom which act, and 
 it is precisely these toxins that are uninfluenced by the serum. 
 Cholera is, therefore, altogether comparable to 'diphtheria and 
 tetanus. In all three cases the microbes multiply at a certain point 
 in the organism, and all the symptoms depend upon the absorption 
 of their toxins. Hence, it was natural to apply to cholera the 
 fundamental principles which guided Behring in the study of diph- 
 theria. This is what was undertaken by Ransom, one of the disciples 
 of Behring, and by Drs. Roux, Metchnikoff and Taurelli-Salimbeni. 
 These authors extracted from cholera cultures a very active soluble 
 poison against which immunity may be conferred by operating 
 progressivelv. A serum is thus obtained which proves active against 
 choleraic intoxication and meets clinical requirements. It is thus 
 possible to prepare two serums against cholera : one acting upon the 
 living element, the other upon the toxin. The latter is efficacious 
 against experimental cholera, which maybe produced in young rabbits 
 by causing them to swallow choleraic cultures. In this, as in the case 
 of man, the process is one of vibrionic intoxication. In the inves- 
 tigations of Metchnikoff, Roux, and Taurelli-Salimbeni, 56 per cent, 
 of the animals experimented upon survived, and 16 per cent, of the 
 controls. In the same order may be mentioned Funck's researches 
 demonstrating that the poison contained in the protoplasm of the 
 typhoid bacillus gives rise to the appearance of germicidal substances 
 in animals. The serum is very efficacious against infection by the 
 living microbes, but exerts no influence upon the typhoid toxins. 
 Chantemesse, on the other hand, by utilizing a special toxin, pre- 
 pared an antitoxic serum. 
 
 It would seem at first sight that nothing is easier of explanation 
 than the mode of action of antitoxic serums. The idea suggesting 
 itself immediately — and such was Behring's idea — is to assume that 
 the antitoxin neutralizes the toxin as an acid neutralizes a base. 
 The serum is supposed to contain a true antidote destroying the 
 
MECHANISM OF IMMUNITY AND OF PREDISPOSITION. r,i;7 
 
 poison. Hence the Hume loxmicidej which is sometime given to it. 
 Behring's conception was combated by Buchner, Ehrlich, !.'■ 
 Vaillard, Calmette, Bouchard, etc. [f a quantity A of serum neutral- 
 izes a quantity B of toxin in such a manner a to render the mixture 
 inoffensive, 2A should neutralize 2B, 3A should neutralize 3B, and •> 
 on. Such is not the case, however. When the quantitie ol erum 
 and of toxin are increased progressively a momenl arrives when the 
 toxin acts. Any amoun.1 of serum may then I"- employed, bul 
 there will no longer be any antitoxic effect. Thus, an inoffensive 
 mixture in the dose of I cubic centimetre will prove fatal it 2 or 3 
 cubic centimetres are injected. We hardly need dwell upon this 
 fact which, from a practical standpoint, is of greal consequi 
 since it explains certain failures of serum therapy. It is also im- 
 portant from a theoretical standpoint, since it proves thai the 
 process is not one of neutralization in the chemical sense of the term. 
 Another objection was formulated by Buchner. This author pre- 
 pared a mixture of tetanus toxin and antitetanic serum. He in- 
 jected it into a mouse without giving rise to any symptoms ; but he 
 discovered that the mixture was still active as regards the guinea-pig. 
 
 When inoffensive doses of the mixture of toxin and serum are 
 introduced the animal may be rendered sensitive to the neutralized 
 poison by modifying its resistance by means of certain microbes. 
 Thus Roux and Vaillard showed that guinea-pigs vaccinated against 
 the vibrio of Massouah take tetanus when they are injected with a 
 mixture of toxin and serum, which mixture is inoffensive for normal 
 guinea-pigs. On the other hand, a normal guinea-pig was inoculated 
 with the same mixture. No symptom was produced, but when, a 
 few days later, the soluble products or various microbes such as the 
 Kiel bacillus or colon bacillus was injected, tetanus was declared. 
 The poison was, therefore, always present. A modification of the 
 organism sufficed to enable it to act. 
 
 Calmette obtained analogous results by means of venoms. He 
 prepared a mixture of venom and serum, and noted that this mixture 
 was inoffensive. He heated it for five minutes at 154.5° F. (6S° C). 
 At this temperature the action of the serum was destroyed, while 
 that of the venom remained intact. He then injected the mixture, 
 which was inactive a little while before, and this time the animal 
 died. There was, therefore, no destruction of poison, but simply a 
 simultaneous presence in the fluid of two substances with antagon- 
 istic action. 
 
568 IMECTIOUS DISEASES. 
 
 The conclusion is evident : Since the antitoxin does not act upon 
 the toxin, it therefore influences the organism itself in such a manner 
 as to enable the cells to resist the action of the poison or, perhaps, 
 not to be penetrated by it at all. 
 
 Passage of Active Substances into the Secretions, and Notably into 
 the Milk. The active substances which are found in the blood 
 of vaccinated animals possess the property of passing into certain 
 secretions, natural fluids, and transudations. This was demon- 
 strated by Stern, 1 Prudden, 2 and Gottstein 3 by studying the serous 
 fluid of vesicatories, of ascites, pleurisy, hydrocele, and the amniotic 
 fluid. Unlike the microbic toxins, which are rapidly eliminated by 
 the urine, as was shown by Prof. Bouchard, the active substances 
 of the serum do not seem to pass into the urine. When an animal 
 is vaccinated its urine possesses no therapeutic property. Such 
 may not be the case when therapeutic serums are injected, since an 
 observation reported by Vagedes shows that tetanus antitoxin passes 
 into the renal secretion. It is detected therein for eleven days. It 
 is difficult, however, to draw a conclusion from this case, since it 
 was that of a patient afflicted with tetanus, and it is not known what 
 role is to be attributed to infection and what to serum therapy. 
 
 The only secretion which is important from a practical standpoint 
 is the milk. Since Brieger and Ehrlich 4 called attention to this fact 
 a great number of experimenters have recognized that the milk 
 contains therapeutic substances, but in quite small amounts. Ehr- 
 lich showed the immunizing power of milk of animals vaccinated 
 against abrin and ricin. Klemperer and Levy established the same 
 fact as regards the typhoid bacillus; but the milk of an immunized 
 goat was ten times less active than the serum of the same animal. 
 Particular researches in this connection have been pursued with 
 regard to cholera and diphtheria. The works of Popoff, Ketscher, 
 and Klemperer demonstrated the passage of anti cholerine into milk. 
 Popoff 5 showed that the active principle is found in the serum of 
 
 1 Stern. Ueber die Wirkung des menschlichen Blutes und anderer Korpersfliissig- 
 keiten auf patogene Mikroorganismen. Zeitschrift f . klin. Medicin, 1890, Bd. xviii. 
 
 2 Prudden. On the Germicidal Action of Blood Serum and Other Blood Fluids. Med- 
 ical Record, 1890. 
 
 3 Gottstein. Zusammenf . Uebersicht uber die bakterienvernichtende Eigenschaft des 
 Blutserum. Therap. Monatshefte, 1891. 
 
 4 Brieger and Ehrlich. Ueber die Uebertragung von Immunitat durch Milch. Deut. 
 med. Wochenschrift, 1892. 
 
 5 Popoff. Uebertragung der Immunitat gegen Cholera mittels der Milch einer vac- 
 
MECHANISM OF IMMUNITY AND OF PREDISP08ITI0N. $09 
 
 the milk and was destroyed by boiling. KetBcher Bhowed thai ih<- 
 milk acts when it, is injected beneath the skin. When it if introduced 
 by the alimentary canal it is inert. The experimenl were made 
 upon vibrionic peritonitis, and, therefore, it v.;i the germicidal 
 stanee that passed ini.D the milk. In order to tudy the antitoxic 
 substance, wo must consider ihe researches pursued with diphtheria. 
 
 Wassermann and Ehrlich 1 employed goats' milk. At the begin- 
 ning of vaccinal ion 5 c.c. were required to neutralize the toxin. 
 Later, 0.1 c.c. sufficed. The serum was twentytimes more active. 
 The authors remark, however, that a goat yield- in one month a 
 litre and a half (a quart and a half) of serum, or 30 litres of milk. 
 It would, therefore, be advantageous to employ the latter -eejetion 
 if it could be concentrated so as to obtain the active substance 
 in a small volume. This is what Wassermanri tried to do. After 
 coagulating the milk by means of lab-ferment, he precipitated the 
 active substance by sulphate of ammonia. The precipitate, dried 
 in vacuo and again dissolved, proved highly effective; 0.125 c.c. 
 of the fluid thus obtained sufficed to neutralize 0.9 c.c. of the diph- 
 theritic poison. 
 
 The employment of milk may, therefore, be of service in thera- 
 peutics. The same is true of eggs. In fact, Klemperer's researches 
 show that anticholerine is found in the yelk of the egg of hens 
 vaccinated against the vibrio. According to Sclavo, the white of 
 the egg contains the diphtheritic antitoxin. Here, therefore, is a 
 new field open to therapeutics. It is not impossible that some day, 
 when active substances will be prepared in a state of purity, milk 
 and eggs of vaccinated animals will replace the serum. 
 
 Germicidal Properties of Tissues. Do the tissues, under the in- 
 fluence of vaccination, undergo modifications analogous to those 
 of the fluids? Such is the question which we endeavored to elucidate 
 after our first investigations on the germicidal properties of serum. 
 The problem was not new. It had long been laid down and taken 
 up by various experimenters, and almost always received a negative 
 answer. The majority of experimenters admit, as a dogma, that 
 microbes develop equally well in all tissues deprived of life, no matter 
 
 cinierten Kuh. Vratch, 1S93. No. 10 (Anal. Centralblatt f. Bakt., 1895, Bd. xvii. 
 p. 166). 
 
 1 Wassermann. Ueber Konzentrierung der Diptherie-Antitosdne aus der Milch im- 
 muuisierte Tliiere. Zeitschrift f. Hygiene. Bd. xvii. p. 233. Ehrlich and Wassermann. 
 Ueber die Gewinnung der Diptherie-Antitoxine aus Blutserum und Milch immunisierte 
 Thieve. Ibid., p. 239. 
 
570 INFECTIOUS DISEASES. 
 
 whether they arc derived from animals enjoying natural or acquired 
 immunity, or not. Unfortunately, the contributions thus far pub- 
 lished arc open to criticism. Bouillon prepared with the muscles 
 of animals has always been employed. It is to be noted that heat 
 destroys the germicidal properties of the fluids, and it must evidently 
 act in the Same manner upon the tissues. Hence, it was necessary 
 to practice cultivation without any previous preparation. The 
 experiment thus conceived was not as simple as might seem at first 
 sight. The majority of aerobic microbes do not develop in the 
 interior of dead tissues where oxygen is lacking. It is difficult, 
 if not impossible, to appreciate with accuracy the intensity of vege- 
 tation inside an organ or a tissue and to recognize whether or not 
 development is similar in animals sensitive to the disease and in those 
 that are naturally or artificially immune. 
 
 All these difficulties disappear when an anaerobic agent is em- 
 ployed, which lives free from air, and the multiplication of which 
 may be appreciated with some accuracy by the amount of gas 
 liberated. These various conditions are fulfilled by the bacillus of 
 symptomatic anthrax. Hence, we have chosen this microbe for 
 studying the problem laid before us. We first investigated the 
 behavior of this bacillus when inoculated into tissues separated from 
 the body and derived from normal, viz., non-vaccinated animals. 
 
 We operated in the following manner: The animal, rabbit, or 
 guinea-pig being killed by hemorrhage, we detached, with every 
 antiseptic precaution, the four extremities. Then, by means of a 
 Pravaz syringe, we injected into each limb from 1 to 5 drops of the 
 serous fluid drawn from an anthrax tumor of a guinea-pig. We thus 
 made four injections with one animal. Immediately after the virus 
 was injected the four extremities were placed in sterilized vessels 
 and put in an incubator with a temperature of 93.2° F. (34° C). At 
 the end of fifteen or seventeen hours it may readily be recognized 
 by palpation that the tissues of the rabbit as well as those of the 
 guinea-pig are infiltrated with gas. This emphysema is really due 
 to the development of symptomatic anthrax and not to putrefaction, 
 since it is not produced in non-infected limbs prepared in the same 
 manner. We are therefore led to conclude that the tissues of the 
 rabbit and guinea-pig present, after death, excellent culture media 
 for the bacillus of symptomatic anthrax. There is no relation 
 between the natural immunity of the animals and the resistance 
 which their tissues, deprived of life, may oppose to the multipli- 
 
MECHANISM OF IMMUNITY AND OF PBEDI8P08ITI0N. :,l \ 
 
 cation of the microbe. This rei nil maj I"- compared to thai ob- 
 served in serum, [t seems, however, lea paradoxical, since the 
 muscles of the guinea-pig are invaded as readily by the microbic 
 agent as those of the rabbit. H is no le int< r< ting to note that, 
 after death, the tissues of a naturally immune animal no longer 
 opposes the development of a pathogenic agenl which could nol 
 develop during life. 
 
 Let us now consider whal occurs in vaccinated guinea pig and 
 in rabbits the natural immunity of which ha been reinforced by 
 means of preventive inoculations. The animal* were treated in 
 the same manner as in I lie preceding experiments: the four limbs 
 worn separated from the body and inoculated al the same time and 
 in the same manner as the limbs of normal animals. At the end 
 of fifteen hours the I issues of (lie latter are infiltrated with gas; 
 those of the vaccinated animals do not contain any. Sometime 
 later it is found thai emphysema develops in the vaccinated limbs. 
 Crepitation is appreciable at the end of twenty-four or twenty-eight 
 hours; but the amount of gas is very small and in now ise comparable 
 to that infiltrating the tissues of the normal limbs. After thirty-six 
 or forty hours the differences are still quite notable. Although the 
 tissues of the vaccinated limbs give the sensation of emphysema, it 
 is easy to see that the tissues of the normal animals are so swollen 
 that even a slight touch will reveal the characteristic crepitation. 
 
 In some of our experiments we took the precaution to irrigate 
 the circulatory system in order to remove all trace of blood before 
 practising inoculation. For this purpose, the animal having been 
 killed by hemorrhage, we first detached one of the thighs. After 
 ligating the vessels opened during this operation, we incised the 
 abdominal wall and injected through a canula introduced into the 
 aorta a 7 : 1000 sterilized salt solution, which came out through 
 the inferior vena cava. The amount of fluid thus employed was 
 360 c.c. The remaining thigh, which had been thus washed, was 
 then detached, and the two limbs were inoculated in the same 
 manner and placed in the incubator. We found that the washing 
 of the circulatory system did not modify the results. It neither 
 restricted nor favored the development of symptomatic anthrax 
 and in nowise modified the differences which are observed according 
 as the tissues experimented upon were those of normal or of vac- 
 cinated animals. 
 
 The procedure employed in these researches is open to some 
 
572 INFECTIOUS DISEASES. 
 
 criticism. It serves to elucidate only one of the phenomena accom- 
 panying microbic development. It may be objected that the bacilli 
 develop in the tissues of vaccinated animals and that only one of 
 their functions is suppressed. Such an objection is not in harmony 
 with the facts known of the biology of anaerobics; at any rate, the 
 objection is of little value. In fact, it matters little whether the 
 vegetation or the function of the microbe is checked. It suffices 
 for us to establish that development differs according as the tissues 
 employed are those of vaccinated or of normal animals. This result, 
 which seems to be undeniable, proves that a chemical modification 
 takes place, no matter whether this modification occurs in the 
 muscles, the connective tissue, or the interstitial fluids. The only 
 legitimate conclusion to be drawn from our investigations — and this 
 is precisely the answer to the question which we proposed to solve — 
 is that the bacillus of symptomatic anthrax develops with difficulty 
 in the tissues of vaccinated animals. 
 
 This conclusion is in harmony with that arrived at by Bitter, 
 who found that extracts of tissues possess germicidal properties. 
 Domssen also learned that the extract of the tissues of rabbits vac- 
 cinated against the pneumococcus possesses vaccinating properties. 
 
 A very skilful experiment of Voswinkel tends to prove that the 
 tissues of certain naturally refractory animals are likewise germicidal. 
 This author experimented upon frogs the blood of which he re- 
 placed by sterilized salt water. He then injected into them 1 c.c. 
 or 2 c.c. of anthrax culture. The microbes introduced soon 
 perished, while those which were kept at the same temperature in 
 salt water preserved their vitality. On studying the phenomena 
 more closely, Voswinkel recognized that while some bacilli were 
 incorporated by some remaining leucocytes, the majority disinte- 
 grated outside them. 
 
 Modifications of the Serum in Animals Predisposed to Infections. 
 After studying the chemical modifications occurring in the organism 
 when its resistance is increased we were naturally led to investigate 
 what happened under opposite conditions. As is known, a great 
 number of procedures may be employed to increase the sensitiveness 
 of animals to infection. This may be realized, for example, by 
 injecting into them the soluble products of streptococci, viz., cultures 
 filtered through a porcelain bougie and not heated. The animals 
 thus treated, when later inoculated, die more rapidly than normal 
 animals. Under these conditions the serum is far less germicidal 
 
MECHANISM OF IMMUNITY AND OF PREDISPOSITIO :,-,:', 
 
 than under normal conditions, Ai tiniei the difference 
 marked that fifteen or twenty hours after inoculation of th< 
 microscopic examination sho^ innumerable germs in the cultures 
 prepared with the serum of the weakened animals, while in those cul- 
 tures made with normal serum only one <>r i wo chains are sieen in each 
 microscopic field. The differences disappear soon after, and, ai the 
 end of two or three days, the two cultures are numerically similar, 
 but not equally virulent. Animals which receive the culture derived 
 from the sera of predisposed animals die before those which re< 
 a culture developed in normal serum. 
 
 The results which we obtained with the serum of predisp 
 animals thus represent the counterpari of those furnished by the 
 study of the sera of vaccinated animals, in the latter case the 
 microbe is attenuated; while in the former instance h is exalted, or 
 rather it seems to be exalted; for some experiments, which ari 
 incomplete, tend to show thai the sera of predisposed animals 
 not upon the microbe, but upon the inoculated animal whose r< 
 ance it reduces. 
 
 The streptococcus is not the only microbe that secret* s predispos- 
 ing substances. Like substances are secreted by the sta] ihyl< icoccus. 
 In this case also the serum, as was shown by Courmont, lose.- its 
 germicidal properties. To use the author's expression, it becomes 
 bacteriophilic. 
 
 Analogous modifications are observed under various circumstances. 
 At times diminution of resistance seems to depend upon a diminution 
 of the alkalinity of the blood. This hypothesis explains how over- 
 exertion weakens the resistance of the white rat to anthrax infection. 
 In fact it is known that the resistance of this animal depends upon 
 the high alkalinity of its blood. The analyses of Drouin demon- 
 strated that this alkalinity diminishes in rats when they are foi 
 to do violent muscular work. likewise, according to Zagari and 
 Innocenti, the alkalinity of the blood is weakened in animals sub- 
 jected to the action of chloral, tartaric acid, and alcohol, and in 
 heated frogs, and in pigeons subjected to fasting. In all cases there 
 is a remarkable parallelism between the diminution in the alkalinity 
 of the blood and the reduction of resistance. The influence of 
 fasting was particularly demonstrated by the experiments of Canalis 
 and Morpurgo. 1 After four or six days of fasting the pigeon lost 
 
 1 Canalis and Morpurgo. Intorno all' influenza del digiuno sulla disposwone alle- 
 malattie infettive. Roma. L890. 
 
574 IXFECTIOUS DISEASES. 
 
 its immunity against anthrax. At this time it possessed very little, 
 if any, germicidal power. In only one experiment the blood re- 
 mained germicidal, and this time the animal preserved its immunity. 
 Gaertner 1 likewise observed that the staphylococcus vegetates more 
 luxuriantly in the blood of rabbits whose resistance to infection was 
 reduced by .means of deficient alimentation and repeated bleeding. 
 On the other hand, if bleeding is only once practised, the resistance 
 is not diminished, even when the loss of blood is great. In accord- 
 ance with this result, the blood remains germicidal, as was shown 
 by Bakunin and Boccardi. 2 
 
 Modifications of the Serum in the Course of Acute Diseases. It 
 might be assumed that the germicidal properties of the serum 
 increase when the individual recovers, and that they diminish when 
 the patient dies. In reality the phenomena are far more complex. 
 Even in fatal cases the organism generally reacts. Therefore, the 
 germicidal properties may increase. From the very start of our 
 researches we noted with astonishment that the serum of animals 
 succumbing to an infection is at times as strongly germicidal as the 
 serum of vaccinated animals and likewise hinders certain functions. 
 The animal dies because the protective substances are insufficient 
 in quantity or have appeared too late. They may nevertheless 
 exert a harmful action upon the microbes that have invaded the 
 organism. Hence, cultures obtained from individuals dead of 
 certain infections may be destitute of virulence. This occurs con- 
 stantly in cases of streptococcic infections. The organism succeeds 
 in attenuating the microbe, but the latter has time to secrete toxins 
 which injure the principal organs and render recovery impossible. 
 Hence, it is not rare to see death occur after destruction of microbes. 
 We therefore remark that in the course of infections two different 
 processes go on simultaneous^. Microbic products are elaborated 
 which tend to diminish the germicidal properties, while the reactions 
 of the organism tend to increase them. We may readily conceive 
 the variability of results according as one or the other process 
 predominates. 
 
 In certain instances the role of reduction of germicidal power in 
 the course of infections has been appreciated. By producing local 
 
 1 Gaertner. Beitrag zur Aufklarung des Wesens des sog. Praedisposition. Ziegler's 
 Beitrage zur patholog. Anat., 1890. 
 
 2 Bakunin and Boccardi. Ricerche su la proprieta battericida del sangue in diversi 
 stati dell' organismo. La Riforma medica, 1891, t. iii. p. 445. 
 
MECHANISM OF IMMUNITY AND OF PRED1 PO XTI01 57fi 
 
 lesions, which subsequently became generalized, Bastin found thai 
 invasion of fche organism is preceded by a diminution of the germ- 
 icidal power. The degree of thii diminution i in dired ratio to the 
 intensity of the infection. On the other hand, in two women suffer- 
 ing from local abscesses, I'nsiin found thai ac regard the taphylo- 
 coccus the blood was more germicidal than normal, and this fad 
 accounted for the Localization of the lesion. Analogous to these 
 results are those obtained by Kiouka, Szekely and Szana, Km-'-. 
 and Pansini. Experimenting with the staphylococcus, bacillus 
 anthracis, and pneumococcus, these authors noticed thai the germ- 
 icidal power diminished and disappeared when infection became 
 generalized — /. <•., when the microbes passed in large numbers into 
 the blood. On the contrary, in typhoid cases the germicidal prop- 
 erties persist until death and the microbes do nol invade the Mood 
 (Kiouka). 
 
 Importance and Significance of Modifications ns I i i ids. In 
 view of the facts reported, it may be concluded that there i- a 
 remarkable parallelism between the variation of the organic n 
 ance and the action of the blood upon bacteria. When the resistance 
 is increased the protective role of the blood is more marked, and vice 
 versa. These correlations are at times so perfect that, as regards 
 the pneumococcus, for example, the serum culture gives the measure 
 of receptivity (Kruse and Pansini). The results are not comparable, 
 however, unless the experiment is pursued upon the same animal 
 species. 
 
 These facts have not, however, sufficed to convince all scieiv 
 Some objections have been raised against the so-called humoral 
 theory which we must briefly consider. We shall not dwell upon 
 erroneous criticisms. It is quite certain, for example, that germ- 
 icidal power does not depend upon a change of medium — i. c. upon 
 transference from bouillon to serum., On the contrary, the germ- 
 icidal action is unmodified when a germ grown in the serum of a 
 normal animal is inoculated into the serum obtained from a vaccin- 
 ated one. 
 
 The important objection is the argument that the germicidal 
 properties do not exist in the blood circulating in the bloodvess 3. 
 They appear when the blood is in an abnormal condition, when it has 
 been coagulated or defibrinated. This is. so to speak, an artificial 
 property developing after death, due. perhaps, to disintegration of 
 leucocytes and to diffusion of substances contained in them. 
 
5 7 6 IXFECTIO US DISEASES. 
 
 It may be replied, in the first place, that it is quite strange that the 
 germicidal, attenuating, or antitoxic power of the serum varies with 
 the degree of resistance, that it is increased when the animals are 
 vaccinated, and diminished when their immunity is weakened. In 
 this maimer the blood of vaccinated animals acquires a new power 
 which is in. a latent state in the organism, and becomes manifest as 
 soon as this fluid leaves the vessels. This power would thus act when 
 it is useless. A good many facts, however, tend to prove that the 
 protective action is real and is readily exercised during life. The 
 passage of active substances into natural effusions, such as the 
 serous fluid produced by vesicatories, ascites, pleuritic, hydrocele, 
 and the amniotic fluids and their presence in milk, cannot be ex- 
 plained otherwise than by the admission that the blood contains a 
 diffusible soluble principle. 
 
 Moreover, there are a few experiments which prove, by other 
 methods, that the protective action really exists during life. This 
 may be demonstrated by protecting the microbes against the phag- 
 ocytes by means of parchment bags, by injecting germs beneath the 
 skin, and after a few minutes studying the modifications presented 
 by them. De Giaxa and Guarnieri introduced the microbe into a 
 segment of artery tied at the two ends. The modifications were 
 found to be the same as outside the organism. Drs. Denys and 
 Leclef injected streptococci beneath the skin of the ear of normal 
 and of vaccinated rabbits. In the former they noted that the 
 microbes rapidly developed and that the leucocytes were not late in 
 appearing at the spot; but, while some of these fulfilled their phago- 
 cytic action, the majority remained passive and did not attack the 
 invaders. In the vaccinated animal, on the contrary, the microbes 
 rapidly disappeared. The number of leucocytes making their appear- 
 ance at the spot was the same as in the former instance, but the 
 microbes were weakened by the serum, and the leucocytes succeeded 
 in devouring them within a few hours. These original and accurate 
 experiments elucidate the various phases of the struggle between 
 the microbe and the organism. Whether the animal is vaccinated 
 or not, the leucocytes migrate with the same facility ; but this afflux 
 of cells is not necessarily followed by phagocytosis. The microbes 
 are more readily picked up because they had been previously affected 
 by the fluids — i. e., by the chemical substances dissolved in the 
 blood serum. Another conclusion to be drawn from these researches 
 is that the active substance in the serum of vaccinated animals can 
 
MECHANISM OF IMMUNITY AND OF PREDI8P08ITI0N. 577 
 
 no longer be considered as a stimulin f exciting the phagocytic pi 
 •of the cells, [t seems rather thai the erum aci upon the microbe 
 by weakening its vitality or by neutralizing the uoxiou ub tancee 
 
 secreted by if. 
 
 Nature and Origin of the Various Active Substances Contained 
 in the Serum. We have indicated the principal modifications 
 presented by the blood in the course or in consequence of infections. 
 Wo must now consider (he relationship exi ting between the various 
 ■substances the effects of which have been alluded to. We musi 
 ask what is the significance and I he cause of germicidal, agglutinat- 
 ing, and antitoxic actions. 
 
 It may first be stated thai certain normal animals furnish agglu- 
 tinating serums, others germicidal serums. Vaccination does not, 
 therefore, produce a new property. On the contrary, it increases 
 or modifies an already existing property. The study of serums 
 obtained from normal and vaccinated animals demonstrates, on the 
 other hand, that there is no constant relationship between the 
 agglutinating and germicidal powers. Thus, the serum of the nor- 
 mal dog agglutinates the bacilli introduced by first inoculation of 
 anthrax, but it does not destroy them. Moreover, numerous obser- 
 vations demonstrate that the agglutinated microbes are not dead 
 and that, under certain conditions, they are capable of development. 
 The two properties may be separated. Heating to 131° F. (55° C.) 
 abolishes the germicidal power, but modifies the agglutinating power 
 very little, if at all. The two substances may also be separated by 
 dialysis. The germicidal substances pass through the collodion sac : 
 the agglutinating substances do not. 
 
 By investigating the relationship existing between the germicidal 
 and the therapeutic powers of serums, Frankel and Sobemheim 
 found that serum heated to 140° F. (60° C.) loses its germicidal 
 action, but preserves its preventive power. It still confers im- 
 munity upon guinea-pigs into which it is injected. Bordet took up 
 the experiment and demonstrated that, by adding a certain amount 
 of normal serum to the heated preventive serum, the germicidal 
 power reappeared. This highly interesting result shows that the 
 serum of a vaccinated animal acts by means of two substances. 
 One is a specific substance resisting a temperature of 141° F. (60° C.) ; 
 the other, present in normal serum, is a common substance which 
 is incapable of destroj-ing bacteria except when the latter have been 
 influenced by the specific substance. In other words, vaccination 
 
 37 
 
578 INFECTIOUS DISEASES. 
 
 causes the appearance of a substance which renders the microbe 
 sensitive to the alexin contained in every serum. 
 
 Continuing the study of these facts, Bordet demonstrated that 
 this specific substance unites with the pathogenic agent against 
 which the animal is immunized. Under its influence the microbes 
 lose theh motility and, in the second phase, they agglutinate. After 
 the remarkable contributions of Bordet, agglutination must be con- 
 sidered a physical phenomenon comparable to coagulation. It 
 results from a change in the relations of molecular adhesion between 
 the bodies of the cells and the fluid containing them. In order for 
 this agglutination to be produced it is necessary for the substance 
 to possess a certain mineral composition, and, notably, contain 
 sodium chloride. When the agglutinating serum is placed in contact 
 with microbes suspended in distilled water the latter remain separate ; 
 when sodium chloride is added they come together and agglutinate. 
 These results are observed not only outside but also within the 
 organism. Frankel and Sobernheim injected into guinea-pigs the 
 serum of a vaccinated animal after heating the serum to 158° F. 
 (70° C). The} 7 ", therefore, introduced a non-germicidal serum. 
 The serum of the animal thus treated acquired the germicidal power 
 which had disappeared from the injected serum. This fact is im- 
 portant, since it demonstrates that we must not, as is often done, 
 believe the properties of the serum to be absolutely unlike those of 
 the plasma. Furthermore, recent researches by Rehm, Camus, and 
 Pagniez seem to demonstrate that the alexins are not artificial 
 products and that they pre-exist in the circulating blood. 
 
 The origin of the specific substance is completely unknown. All 
 that is known about it is that it is not produced or contained in the 
 leucocytes. 
 
 The investigations of Deutsch demonstrated that the liver, kidneys,, 
 and suprarenal capsules contain very little agglutinin. The spleen, 
 the lymphatic glands, and the bone-marrow contain more, but the 
 amount is still less than that found in the blood. On the other hand, 
 the lungs contain more of it, but these organs also contain it nor- 
 mally. It would be interesting to learn whether the lungs play an 
 important role in the formation of this substance. As to the alexins, 
 the researches of Denys, Havet, and Hahn have conclusively shown 
 that they proceed from the leucocytes. But there is another 
 problem connected with this subject. Do the white blood cor- 
 puscles alone elaborate alexin? Cannot other cells also participate 
 
MECHANISM OF IMMUNITY AND OF PM DJ PO 1 1 in; 579 
 
 in this function? Kven supposing thai the leucocytes are th< 
 producers of the germicidal substance, i i1 to !"• pre umed thai 
 they retain it in their interior and thai il erve only to d< 
 the microbes ingested by the leucocyte ? When it 1 encountered 
 in various fluids, is it to be suppoi ed, following Metchnikoflf'a school, 
 that alexin diffuses only after the destruction of leucocytes? Or is 
 it to be admitted, as does Buchner, thai it \t constantly given off 
 as a secretion? This is the only poinl upon which the adherenta 
 of the so-called humoral and cellular doctrines of immunity are not 
 agreed. The question is undoubtedly of greal importance from a 
 theoretical standpoint. If the germicidal substances remain en- 
 closed within the leucocytes, phagocytosis retains ite importance. 
 If they diffuse, the phenomena of extracellular digestion become 
 predominant and the modifications of the humore assume an im- 
 portant position. It is well to remark, moreover, thai even suppos- 
 ing that the germicidal substances do not leave the leucocyt 
 and this hypothesis seems to us contradicted by certain facts above 
 reported, since the sensibilizing substance is not of leucocytic origin 
 —the modification of the fluids explains all acquired immunity. 
 The phagocyte is capable of digesting only those microbes which 
 have been acted upon by the specific substance, viz., that substance 
 which is found in fluids modified by infection. Thus, owing to the 
 fine contributions of Bordet, we return to the conception of acquired 
 immunity as it was understood years ago by Bouchard and his 
 disciples. 
 
CHAPTER XX. 
 
 CONGENITAL INFECTIONS AND HEREDITY. 
 
 Passage of Microbes through the Placenta. The Law of Brauell-Davaine. Experi- 
 ments upon Anthrax Infection. Transmissibility of Some Human Infections. 
 Congenital Variola. Peculiar Characters of This Clinical Form. Course of Tem- 
 perature in Congenital Variola. Its Analogy with Experimental Variola. Trans- 
 mission of Chronic Infections: Leprosy, Syphilis, and Tuberculosis. Congenital 
 Dystrophies of Infectious Origin: Role of Syphilis and of Tuberculosis. Trans- 
 mission of Immunity. Laws of Colles and of Profeta. Role of Father and <>f 
 Mother in the Transmission of Immunity. Conclusions. 
 
 The history of heredity of infectious diseases 1 must be considered 
 from a triple standpoint: transmission of the living microbe from 
 parents to progeny; transmission of modifications in fluids and cells, 
 namely, chemical or dynamic changes occurring in the organism of 
 the parents in the course or in consequence of infections ; influence of 
 diseases of the parents upon the development of the child during and 
 after intrauterine life. 
 
 Passage of Microbes through the Placenta. 
 
 Let us first consider the simplest question: the contamination of 
 the fetus by living germs. Clinical observation has long demon- 
 strated the reality of fetal infections; it will suffice to cite variola 
 and syphilis. There are, however, other infections in which the prob- 
 lem is more complex and more difficult of solution. The explanation 
 of inherited tuberculosis has given rise to numerous contradictory 
 works upon the subject. Some writers have asserted the possibility 
 of fetal contamination by the father or by the mother; others, pur- 
 suing the discussion on similar lines to those which apply to syphilis, 
 have described cases of early or of tardy heredity, while still a third 
 school has totally rejected the idea of direct transmission and held 
 tubercular heredity to be nothing more than a congenital predispo- 
 sition to contract the disease. According to the last-mentioned 
 hypothesis, it is not the bacillus but the soil favorable to its develop- 
 ment that is transmitted. 
 
 1 Roger. L'h6r6dite dans les maladies infectieuses. Gazette hebdomadaire, October 
 11, 18, and 25, 1889. 
 
CONGENITAL INFECTIONS AND HEREDITY. :,-\ 
 
 Experimental pathology has taken up the problem, and the number 
 of works bearing upon this question i very considerable. Prom ;> 
 general point of view, we may firsl cite the magnificenl researches 
 
 upon discuses of (he silkworm. Ii i known thai these worm 
 liable to two main infections: pebrinand Bacherie. Pebrin i fci 
 mitted from generation to generation through theegge which contain 
 the pathogenic agent. The lal ter is incorporated with the egg inside 
 
 the female chrysalid, .- 1 1 1 < I heroines .'in integral pari '<r the embryo 
 and the worm evolved From it. The male doei no1 transmil the 
 disease, but it may exercise upon the progeny a harmful influence 
 
 as expressed by weakness of I Ik- worm and the inferior quality of its 
 cocoon. In flic case of llaclierie flic agenl of the disease resides in 
 the intestine and does not invade the eggs. The worms issuing from 
 
 contaminated animals do not have the disease, bu1 they are weak 
 and almost certainly predestined to become victims of the contagion. 
 It is the morbid predisposition that is transmitted. Do we not find 
 in the history of these affections of the silkworm the counterpart of 
 what occurs in syphilitic and tuberculous infections of more highly 
 developed organisms? 
 
 Intraplacental Transmission of Anthrax. It was with anthrax, 
 the experimental disease par excellence, that the first attempt was 
 made to solve the problem whether or not infectious germs may pass 
 through the placenta and invai le the fetus. Brauell, in 1858, reported 
 four experiments upon a colt and three sheep. Microscopic exam- 
 ination showed no bacilli in the fetus, and inoculation into animals 
 gave rise to no symptoms. Davaine added one, and Bollinger, in 
 1876, reported three more negative results. The question then 
 seemed to be settled and the law of Brauell-Davaine.that the placenta 
 was a perfect filter, was admitted. A first opposition was raised hv 
 Arloing, Cornevin, and Thomas, who were convinced that sympto- 
 matic anthrax was transmitted from the mother to the fetus. In 
 1882 Straus and Chamberland published a few facts which seemed 
 to confirm Branch's law: but, by pursuing their studies. these authors 
 later recognized that such transmission was at times possible. They 
 experimented upon twenty guinea-pigs ; microscopic examination of 
 the blood, liver, and the spleen revealed no bacilli. The fetus pre- 
 sented no alterations whatever, and the blood did not offer the agglu- 
 tinating property which is observed in animals dead from anthrax. 
 But the result was altogether different when the authors employed 
 another method — i. c, when thev resorted to cultures and intoxica- 
 
582 INFECTIOUS DISEASES. 
 
 tions. They thus obtained several positive results, especially by cul- 
 i ivation, since inoculations quite often failed. On examining twenty- 
 six fetuses they detected the bacillus anthracis in fourteen of them. 
 Their investigations established the fact that in certain rare cases 
 anthrax is not transmitted to any of the fetuses of the same litter; 
 in other instances the disease attacks all of the fetuses; in most cases 
 it affects only some of them. At all events the number of bacilli 
 penetrating the fetal organism is extremely small; this fact accounts 
 for the negative results obtained by the first investigators. The ex- 
 periments of Straus and Chamberland gave rise to a great number of 
 researches which confirmed the conclusions of the two French scien- 
 tists. Such were those of Perroncity, Koubassoff, Birch-Hirschfeld, 
 Rosenblath, and Latis. 
 
 There are also some interesting observations as regards man. 
 Marchand reports the case of a woman who died from anthrax a few 
 hours after confinement, and her child succumbed to the same infec- 
 tion four days later. There were numerous bacilli in the placenta 
 and ulcerations in the chorionic villi. Paltauf reports a case in 
 which bacilli were found in the lungs of a fetus of five months from 
 a woman suffering from anthrax. In two cases observed by Eppinger 
 and in another by Morisani the results were negative. It may be 
 concluded from all these experiments and from the observations thus 
 far published that the bacillus of anthrax may pass through the 
 placenta ; but the fact is far from being constant, and the number of 
 bacilli invading the fetus is always very limited. We now appreciate 
 why the bacilli were not found by microscopic examination except 
 in a few cases. 
 
 It is quite difficult to determine the frequency of intraplacental 
 transmission of anthrax. At any rate, in this case, as in all other 
 cases of this kind, statistics can give no more than illusive results 
 and present no interest from a scientific standpoint. The bacillus 
 anthracis passes into the fetus in a variable manner because the 
 conditions which seem apparently identical are in reality dissimilar ; 
 the animals react differently, according to a multitude of circum- 
 stances which are often very difficult to explain. In other words, the 
 experiment is modified by various conditions which favor or hinder 
 this passage. The experimenter, therefore, instead of discussing the 
 frequency of the phenomenon, should endeavor to learn why and 
 especially how it is produced. We are, therefore, indebted to Dr. 
 Malvoz, who attempted to explain the mechanism by which the intra- 
 
CONGENITAL INFECTIONS AND HEREDITY. 
 
 placental passage of anthrax takes place. The research* of this 
 author show that the indispen able condition re ide intheexi tence 
 of placental alterations. Hence, i1 i intelligible why non pathogenic 
 microbes, such as the bacillus prodigio u . are incapable <>f pa 
 the barrier. The same is true of inerl iufa tai a ich ■■> sulphate 
 of barium and [ndia ink; it' other bodies can pa i1 i owing to 
 lesions produced by solid or resisting substances. I' may, ther< 
 be said in conclusion that no passage of figurate elements occurs 
 without alteration in the placenta. Moreover, Malvoz remarks thai 
 the bacilb' are transmitted to the fetus more easily in the guim 
 than in the ral >l >il , .-i , fad which is < xplained by the greater frequency 
 of placenta] alterations in the former of these animals. 
 
 Those very interesting experiments give no final solution of the 
 problem; they only Ie:ul lo (he in acs ligation of the conditions which 
 favor placental alterations which, under apparently identical condi- 
 tions, give rise to different lesions. The problem is undoubtedly a 
 difficult one; but it is a satisfaction to have its terms laid down and 
 to see how successive discoveries tiring out new complications in the 
 question. 
 
 Intraplacental Transmission of Human Infections. We have thus 
 far considered microbes especially attacking lower animals; we now 
 come to those which are of greater importance for human pathology. 
 
 The study of the streptococcus is extremely interesting, owing to 
 the fact that it is the most frequent agent of puerperal septicemia. 
 Lorrain had already observed peritonitis in children born of septic 
 women. The observations of Simone, Lebedeff, Hanot. Luzet, Haus- 
 halter, and others demonstrate the intraplacental transmission of the 
 streptococcus. A case observed by the author seems to demonstrate 
 that the death of the fetus does not occur in every case. A woman 
 suffering from measles gave birth to a child of eight months weighing 
 four and one-quarter pounds. The author obtained a pure culture 
 of streptococcus with the blood of the umbilical cord: the child had 
 an attack of icterus, but it soon recovered, and a month later, when 
 it left the ward, it weighed five and one-quarter pounds. It had not 
 only withstood the streptococcic infection revealed by the culture, 
 but even gained a pound in weight. 
 
 As has ahead} 7 been stated, the child does not seem to be infected 
 in the course of erysipelas. In twelve cases women suffering from 
 erysipelas were delivered at full term, and all the children survived 
 without presenting any notable disorder. 
 
584 IXFECTIO US DISEASES. 
 
 The existence of congenital pneumonia has long been admitted, 
 Grisolle asserts that this affection is not rare in the newborn, and 
 that it ends fatalty within a few hours, when autopsy will reveal 
 disseminated foci and even abscesses in the lung. The last-men- 
 tioned condition renders somewhat doubtful the nature of the disease 
 transmitted and suggests rather the idea of pj^emia with pulmonary 
 involvements. Netter, who pursued interesting researches on this- 
 subject, reported, in 1886, the transmission of the pneumococcus in 
 guinea-pigs ; of four fetuses the issue of a contaminated mother, two 
 contained the microbe. Analogous facts have been observed by Foa. 
 and Uffreduzzi in the rabbit and Ortmann in the guinea-pig. The 
 transmission of the pneumococcus is, therefore, possible in animals 
 as well as in the human species. Thorner reported a case in which 
 the mother was confined at full term after defervescence of pneu- 
 monia; the child succumbed in thirty-six hours, and the autopsy 
 revealed hepatization of the lower left lobe, and the microscopic exam- 
 ination detected the pneumococcus. The most complete observation 
 is Netter's. In this case the child succumbed after five days. This 
 lapse of time might lead to the suspicion that perhaps a contamination 
 had taken place after birth. However that may be, the lesions were 
 very marked, consisting in hepatization of the right apex with pleu- 
 ritic and pericardial pseudomembranes and fibrinopurulent exudates 
 in the meninges. This was, therefore, a case of infectious pneumonia 
 the nature of which was demonstrated by bacteriological examina- 
 tion; the generalization of the lesion is readily accounted for by the 
 direct entrance of the morbid germs into the blood. Bacteriological 
 investigations may likewise detect the pneumococcus in fetuses from 
 mothers suffering from any one of the various affections which may 
 be produced by this microbe. Netter cites an observation of Hecker 
 concerning a woman who died of a suppurative meningitis ; the child, 
 delivered by a Cesarean operation, died at the end of thirty-four 
 hours, and the autopsy showed left lobar pneumonia with pleuritic 
 and pericardial effusions. The author had the opportunity to observe 
 a pregnant woman suffering from measles and intense bronchitis. 
 She gave birth to a child of eight months which succumbed a few 
 hours after birth. Pine cultures of pneumococcus were obtained 
 from the blood and organs of the fetus, and the same microbe was 
 found in large numbers in the expectorations of the mother. Here 
 is an example of an infection which, in spite of its benign character 
 and its apparently exclusive location in the bronchi, had really 
 
CONGENITAL INFECTIONS AND HEREDITY. 
 
 infected the maternal organism, since the pathogenic agent had 
 
 invaded the fetus and mused its death. Friedlander'i microbe al o 
 may, according to Nefter, be bran imitted to the fetu , On the other 
 hand, Foaand Rattone believe thai it favori abortion, bu1 doe doI 
 pass to the placenta. In pregnanl guinea pigs inoculated through 
 the peritoneum, abortion occurred within thirt} is or forty-eighl 
 hours, and no microbes were found either in the fetut or in the 
 placenta. 
 
 While speaking of lnmian diseases we may mention typhoid f< 
 since the transmission of this Infection to the fetus reems to be well 
 demonstrated by recent observations. Eberth's bacillus, penetrat- 
 ing directly into the blood, kills the fetus by inducing septicemia. 
 This is a new illustration of symptomatic variations which may be 
 observed according to the age of the subjects or the mode of entrance 
 of the virus. 
 
 With reference to cholera, we may cite an observation of Tizzoni 
 and Cattani upon a woman suffering from this infection who - 
 birth to a fetus of five months. In this case, as in the majority of 
 other diseases, microscopic examination did not detect the presence 
 of any microbe, while cultivation enabled the experimenters to find 
 the comma bacillus. 
 
 Recurrent fever has also been known to be transmitted to the 
 fetus, and in this instance Spitz was able to discover Obermei<i '< 
 spirilla in the embryo. It must also be remembered that the trans- 
 mission of intermittent fever to the fetus seems to have been estab- 
 lished by some of the older observers. Stokes recorded the case of 
 a pregnant woman suffering from tertian paroxysms whose child had 
 convulsions on the days when the mother enjoyed apyrexia. Pities 
 and Aubanais have seen malarial mothers giving birth to children 
 which presented hypertrophy of the spleen and febrile paroxysn - 
 the same daj^s and hours as their mothers. Schurig, Hoffman, and 
 Russel have published similar observations. Among the infectious 
 diseases the pathogenic agents of which are unknown or little known 
 we may cite acute articular rheumatism (Follack and Schaeffer) and 
 especially hydrophobia, which are sometimes transmitted to the 
 fetus. 
 
 The transmission of the hydrophobic virus was first demonstrated 
 by clinical observation. Lafosse saw a rabid cow give birth to a 
 calf which presented the first symptoms of hydrophobia three days 
 after birth. Perroncito and Carita have recently studied this ques- 
 
586 INFECTIOUS DISEASES. 
 
 tion from an experimental standpoint: A rabbit which had been 
 inoculated with hydrophobia gave birth to a litter of four. One day- 
 prior to the appearance of paralytic symptoms the spinal cord of 
 two of the young ones was inoculated into two guinea-pigs, one of 
 which developed hydrophobia, the other resisted. The transmission 
 of the virus -of hydrophobia, however, seems to occur but exception- 
 ally. Moreover, it is known that the blood has nearly always been 
 found free from infecting properties, and, on the other hand, it is 
 well established that only those microbes that can invade the blood 
 are capable of penetrating the placenta. Several experiments were 
 made in the Pasteur Institute with negative results. The medulla 
 of eight of the young born of hydrophobic animals were inoculated, 
 and none of these medullas proved virulent. It may, of course, be 
 objected that perhaps in the fetus the virus does not reside in the 
 nervous centres. This objection is refuted by Zagarri's experiments. 
 This author operated upon fourteen pregnant females inoculated with 
 the fixed virus; thirty-two young ones were thus obtained for the 
 experiments. The nervous centres, liver, sometimes the entire fetus 
 were used, but the inoculations practised upon rabbits and guinea- 
 pigs produced no results. 
 
 Transmission of Eruptive Fevers. 
 
 Vogel, Heine, Rilliet and Barthez published several cases of con- 
 genital measles, the mother having been attacked before confinement. 
 We know also of a few cases of congenital scarlatina recorded by 
 more or less ancient authors — Baillou, Ferrario, Portier, and others. 
 Such facts must be very rare, since the author has never observed a 
 case of congenital measles or scarlatina. 
 
 Congenital Variola. Variola is the disease which has furnished 
 the greatest number of observations of congenital infection. The 
 facts observed are the more valuable, as the child on coming into 
 the world sometimes presents characteristic lesions and there can, 
 therefore, be no doubt as to the nature of the disease. A few cases 
 possess the certainty of an experiment and have served purposes of 
 inoculation with positive results (Gervis, Jenner). Hereditary vari- 
 ola is particularly frequent when the mother contracts the disease 
 toward the end of gestation. As in the case of anthrax, in twin 
 births the contamination of only one of the infants is a possible event. 
 In the observation of Kaltenbach, a woman suffering from variola 
 was delivered of three children; two of them had pustules, the third 
 
CONGENITAL INFECTIONS AND HEREDITY. 587 
 
 did not. No!, infrequent ly the variola of the fetu i more recenl than 
 that of the mother; the latter may be convale cenl and give birth 
 
 to a child bearing fully developed pu i'il< . Iii :i t'v. ca e the fetus 
 h;iH contracted the disease while the mother remained exempt. 
 Finally, even when there is no tran mi ion, properly o called, and 
 the fetus presents no alteration its organism may have been pro- 
 foundly modified under the influence of the maternal disease, and 
 thus it is born vaccinated, baving acquired immunity in the ut 
 
 Such are the results admitted by all classical authoriti 
 observations am not in harmony with the descripl ion thus far given. 
 During the epidemic of 1901, eighteen women wire confined in OUT 
 hospital. The children never presented al birth the slightest erup- 
 tion. One of them manifested no disturbance whatever, and flour- 
 ished. The others appeared a,l first to be exempt, but a more atten- 
 tive observation revealed a certain number of disorders, showing 
 that, notwithstanding the absence of easily appreciable symptoms, 
 these children were all variolizcd. 1 The germ of variola had con- 
 stantly passed through the placenta. Infection was produced 
 whether the maternal variola was discrete and curable, as was the 
 case in six of them, or fatal, as occurred in the other patients. The 
 passage of the germs is rapidly effected. One of the children was 
 born a day before the mother was taken sick; another a few hours 
 after invasion; three others a day after. In eleven cases confinement 
 occurred on the second or the third day of the disease, that is, a 
 little before the eruption or coincidently with it, and once eight days 
 after. Three children were born at seven months, the others at full 
 term. At first they seemed to be normal, and nothing would have 
 suggested a congenital infection if their temperatures had not been 
 taken. The information thus obtained was unexpected. All these 
 children were hypothermic; in no case did the thermometer, intro- 
 duced into the rectum, rise to 98.6° F. (37° C); in most cases it 
 remained below 96.8° F. (36° C). In some instances it fell rapidly 
 to 87.8°, 86°, and even 82.4° F. (31°, 30°, and 2S° C). This hypo- 
 thermia seemed to express a profound infection which had over- 
 whelmed the organism. If the child is sufficiently resistant and 
 capable of reacting, the temperature rises and may reach normal or 
 even 104° F. (40° C). In the latter case there are also observed 
 cutaneous manifestations expressing an effort of the organism to 
 
 1 Roger. Variole des nouveau-iies. Soc. mod. des hopitaux. March 29, 1901. 
 
588 
 
 IXFECTIOUS DISEASES. 
 
 seven months 
 
 eject the morbid element. According as these reactions appear or 
 are absent the observations may be divided into two groups. 
 
 The first group contains six cases in which the children suc- 
 cumbed without presenting any symptom indicative of variola. 
 A woman suffering from hemorrhagic variola to which she suc- 
 cumbed on the eighth day had, on the day prior to the invasion, 
 given birth to a child at full term weighing six and one-half pounds. 
 At the time when the child was admitted to our wards, that is three 
 days after birth, it presented a rectal temperature of 96 F. (35.6 C.) . 
 It was suffering from a slight icterus, which became aggravated the 
 following day, when the child succumbed with a temperature of 
 96.4° F. (35.8° C). The second case was that of a child born at 
 The mother had a discrete variola from which she 
 easily recovered. The child was born on the third 
 day of the mother's disease, the day following the 
 eruption. Two days after birth it developed a 
 slight icterus. Its temperature fell on the fifth day 
 to 86° F. (30° C). Then, as if a reaction was com- 
 ing, it rose rapidly, and in two days reached 98.6° F. 
 (37° C), when the child died. (Fig. 40.) The other 
 cases were analogous. Death may supervene very 
 rapidly ; thus a child born at seven months of a 
 mother suffering from hemorrhagic variola, to which 
 she succumbed sixteen hours later, lived only five 
 hours. Its rectal temperature, taken ten minutes 
 after birth, was 87.8° F. (31° C). 
 
 In such cases the symptomatology consists in a 
 subnormal temperature and icterus. It may, there- 
 fore, be questioned whether we are not in the pres- 
 ence of weak children and whether we have any 
 right to speak of variolar infection. The analysis 
 of the second group of cases will enable us to answer 
 this question. We shall first cite the case of a child 
 born at full term. The mother developed on the 
 day of her confinement the first symptoms of a hemorrhagic vari- 
 ola, to which she succumbed on the eighth day. The temperature 
 of the child at first oscillated around 96.8° F. (36° C.) ; it rose on 
 the ninth day to 100.7° F. (38.2° C), to fall again the next day to 
 98.6° F. (37° C). On that day a scarlatiniform erythema made its 
 appearance and covered the whole body, being more marked on the 
 
 Fig 
 
 40 
 
 
 
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 Congenital variola. 
 
CONGENITAL INFECTIONS AND HEREDITY. 
 
 
 face. The child seemed to I"' in a satisfactory condition, l>ut it 
 suddenly died in syncope the following night. In the other ob er- 
 vations the evolution was more complete; il terminated in the d 
 opment of a characteristic eruption which in most ca i quite 
 
 discrete, and sometimes remained al the papulou phase. This 
 occurred in four cases. 
 
 The temperature may rise a high at in the adult. A child had 
 104° F. (40° C.) on the thirteenth day coincidenl with the appearance 
 of a few papules on the body. Death Bupervened the following 
 
 In several cases I he eruption Hue remained al the stage of papules, 
 either because; the evolution was suddenly interrupted by death or 
 because the elements were rapidly dried. Purulenl transformation 
 is possible, however. A well-developed child was born al full term; 
 
 
 Fio. 41. 
 
 S 8 « ."> 
 
 a s !> iu ii u la it 
 
 101" 
 
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 -t i 
 
 
 
 Congenital variola. 
 
 the mother had suffered for three days from hemorrhagic variola, to 
 which she succumbed six days later. The rectal temperature of the 
 child, which was 95° F. (35° C), rose on the following days. At the 
 same time icterus developed. Then a febrile movement occurred on 
 the tenth day, during which the temperature reached 104° F. (40° C). 
 A crop of about fifteen papules appeared upon the back. face, and 
 hands. The child emaciated and refused the bottle. The evolution 
 of the eruption continued. The fever, as in the variola of the adult, 
 fell to rise again, and its renewal coincided with a purulent transfor- 
 mation of the eruption. This fever of suppuration was suddenly 
 interrupted on the twentieth day by a final hypothermia. (Fig. 42. 
 Here is a case in which the evolution is similar to that in the adult. 
 It differs, however, in two important characteristics — an initial 
 
590 
 
 / NFE( •Tinl TS DISEASES. 
 
 hypothermia and discrete eruption contrasting strikingly with the 
 gravity of the general phenomena. 
 
 Whatever may be the clinical form of the infection, the results 
 shown by the necropsy are fairly uniform. As in the adult, there 
 are frequently found degenerations of the liver and kidneys and small 
 hemorrhages on the surface of the viscera, notably of the kidneys. 
 In one case the suprarenal capsules were the seat of a diffuse hemor- 
 rhage. Histological examination reveals profounder lesions; myo- 
 carditis is very frequent and assumes the same characters as in the 
 adult. The liver is profoundly altered, and the changes in its cells 
 
 Fig. 42. 
 
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 7 s 1 a 
 
 10 
 
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 13 
 
 14 
 
 15 
 
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 Congenital variola. 
 
 may perhaps account in part for the frequency and persistence of 
 hypothermia. Although grave, the disease is not necessarily fatal. 
 A child which once had a temperature as low as 91.4° F. (33° C.) 
 recovered. This favorable evolution is probably due to the fact that 
 the mother had been revaccinated in the seventh month of her preg- 
 nancy. Two pustules developed. This vaccination was, however, 
 insufficient to establish complete immunity, since this woman was. 
 attacked two months later by a discrete variola from which she easily 
 recovered. Confinement took place at full term, two days after the 
 onset of the disease and twenty-four hours before the development 
 of the eruption. The child, well constituted, weighed six and one- 
 
CONGENITAL INFECTIONS AND HEREDITY. 
 
 591 
 
 half pounds, [t was vaccinated withoul ucce the day following 
 its birth. In spile of its fine appearance and the fad thai it took 
 nourishment satisfactorily, this child was hypothermic; it rectal 
 temperature oscillated around 95° P. (35° C.) and even fell to 93 2 I 
 (34° (!.). Eleven days after birth the temperature suddenly fell to 
 91.4° F. (33° C). In the eveningit rose to 99.2° I . (37.3 ' . and 
 a slight erythema appeared on the skin with three papule , two on 
 the arm and one on the neck. Three days later the papules were 
 dry and the child seemed convalescent, bul on the sixteenth day 
 the temperature again fell to 95° I'. (35° C), to again rise. Tin.-, 
 thermal variation coincided with Hie appearance of a 3econd eruption 
 consisting of three papules situated on the scalp, the thigh, and the 
 
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 Congenital variola. Recoverv. 
 
 leg of the same side. Two days later two new papules were found 
 on the arm and three upon the abdomen. The total number of 
 eruptive elements was eleven. The general condition was serious, 
 but the child took nourishment fairly well. The following days the 
 papules dried, and an improvement seemed to follow, but on the 
 twenty-fourth day a new hypothermia was observed accompanied 
 with vomiting and diarrhea. Under the influence of subcutaneous 
 injections of artificial serum the temperature rose and reached normal 
 in a definitive manner on the thirty-first day. At the same time the 
 other disturbances disappeared and the child became convalescent. 
 This brief description showed that the variola of the newborn differs 
 totally from that of adults. It is announced by hypothermia, which 
 
59 2 I MIX 'TIO US DISEASES. 
 
 is in some cases slight, in others very pronounced. Jaundice appears 
 (in only one of the eleven children it was absent). Then two evolu- 
 tions are possible: either the child will become weak and die in 
 hypothermia, without presenting other symptoms, or else an eruption 
 develops, generally coinciding with a rise in temperature. It some- 
 times consists in a simple rash, but more often presents small papules. 
 The eruption recurs several times, but it is almost always very 
 discrete. Among those who succumbed, three only had an abundant 
 eruption. The eruption may evolve as in the adult, but this is 
 exceptional; the papules do not suppurate, but soon dry and are 
 covered with small crusts. Recovery is exceptional, and death super- 
 venes from the fourteenth to the twenty-first day by gradual weak- 
 ening or syncope. The profound lesions of the myocardium explain 
 the sudden termination. 
 
 This peculiar evolution of congenital variola is of considerable 
 theoretical interest. In fact, it recalls the description of variola in 
 the rabbit, such as we have described it with Dr. Weil. We know 
 by many examples that the pathology of the first period of life is 
 often analogous to the pathology of animals. Thus, tuberculosis 
 takes a course in young children similar to that in the small rodents 
 utilized in laboratories. The same is perfectly true of variola : rabbits 
 inoculated with variolar pus generally succumb without producing 
 any eruption; when they present any it consists, as in newborn 
 children, of a limited number of disseminated papules which become 
 covered with crusts without suppuration. Like children, the animals 
 become emaciated and weakened and succumb in hypothermia. It 
 is not only because the reactionary modes are analogous in the new- 
 born and in animals that the evolution is comparable, but also 
 because in both cases infection is thorough and overwhelming. In 
 animals we inject relatively large quantities of the virus ; in the fetus 
 the microbes also penetrate in large numbers, as has been proved 
 by the examination of the amniotic fluid. The study of the blood 
 leads to similar conclusions. From the child who died three hours after 
 birth we took a drop of blood immediately after death. This blood, 
 examined with the assistance of Dr. Weil, had the following formula : 
 
 Polynuclears 17.0 per cent. 
 
 Mononuclears 63.5 " " 
 
 Large mononuclears 7.5 " " 
 
 Xfutrophile mononuclears 10.0 " " 
 
 Eosinophile mononuclears 1.0 " " 
 
 Eosinophiles 0.5 " " 
 
 Irritation cells 0.5 " " 
 
CONGENITAL INFECTIONS AND HEREDITY. 
 
 There were; also found a great number of nucleated red corpu i 
 Without dwelling upon theoretical consideration which the study 
 of variola in t.l 1 r ; newborn gives rise to, the author believe thai the 
 knowledge of its peculiar evolution is of certain practical inti 
 The (■li.'ir.'i.ciiTK of Hie fever fhart and of the eruption imparl to il 
 a particular physiognomy and assure it a eparate po ition in the 
 clinical forms of this infection. 
 
 Intraplacental Transmission of Chronic Infections. 
 
 It now remains to study the chronic infections, syphilis, tubercu- 
 losis, and leprosy. The heredity of syphilis has been more thoroughly 
 investigated than that of any other disease, owing to the fact that 
 in this malady the mode of contagion is in general easily determined, 
 while in the case of tuberculosis interpretations are often diffieult. 
 In the case of a tubercular child the question may always be raised 
 whether it inherited the disease or whether it was infected after birth 
 while living with its parents. Of course, syphilis may also be con- 
 tracted under the same conditions, but then the existence of a pri- 
 mary lesion indicates the origin of the infection and suffices to remove 
 all doubt. Hereditary transmission of syphilis is particularly fre- 
 quent when both parents are affected and the disease is recent. 
 After two or three years infection of the fetus occurs more rarely, 
 although it is a possible event for a long period of time. When only 
 one of the parents is contaminated the fetus may still be infected; 
 but maternal heredity is far more important than paternal. The 
 father less surely transmits syphilis; the inoculations practised by 
 Mireur have established in fact that the semen is not virulent. When 
 the father alone is contaminated the fetus dies toward the sixth or 
 seventh month and pregnancy is terminated by miscarriage. If, how- 
 ever, the child is born at full term it is often found to be free from 
 or only slightly infected by the disease in the case of maternal 
 syphilis. Moreover, some recent observations tend to demonstrate 
 that syphilis may be transmitted during two generations ; this is what 
 results from the facts published by Lannelongue, Founder, and 
 Besnier. 
 
 In most cases the mother is infected before or during the fecun- 
 dation; occasionally, however, she contracts the disease during preg- 
 nancy. What happens to the fetus? This question has been va- 
 riously answered. Mandrou and Kossowitz have denied the heredi- 
 tary transmission of syphilis after conception, while Cullerier is of 
 
 38 
 
594 INFJ2C TIO US DISEA SES. 
 
 the opposite opinion. It seems that it may really occur, but only 
 when the infection has been acquired before the sixth (Ricord) or 
 the seventh month (Albernethy, Pidoux). After this epoch the fetus 
 remains exempt, and this may readily be accounted for by the fact 
 that at the beginning of infection syphilis remains localized at the 
 point of inoculation, and does not pass the limits of the lymphatic 
 system. 
 
 The manifestations of hereditary syphilis have been divided by 
 Fournier into two groups according as there is transmission of the 
 virus or parasyphilitic symptoms appear. In the former instance the 
 manifestations are similar to those in the adult; the difference con- 
 sists only in the absence of the initial lesion, which fact is due to 
 the direct infection of the blood. This mode of penetration of the 
 pathogenic agent likewise explains the great rapidity of the evolution 
 and the consequent confusion of the phenomena which it is still 
 customary to divide into secondary and tertiary. We hardly need 
 recall that syphilitic accidents may appear at very different periods 
 of life; sometimes clinically appreciable manifestations exist at the 
 time of birth; more frequently they appear toward the sixth week; 
 at times they appear tardily at the age of thirteen or even fifteen 
 or twenty years of age. Parasyphilitic manifestations shall be 
 studied later in connection with nutritional disturbances which may 
 occur in other infections. 
 
 The history of syphilis likewise furnishes the solution of several 
 problems which, from the standpoint of general pathology, are of 
 great interest. Although it is the mother who commonly transmits 
 the disease to her product, there are incontestable cases in which it 
 has been inherited from the father, the mother remaining absolutely 
 sound. Even in such a case, however, the maternal organism is 
 modified. The woman who gives birth to a syphilitic child may 
 suckle it with impunity, since she is in no danger of contagion. How 
 is this fact to be interpreted? Is the maternal organism impregnated 
 by products secreted by the microbe of syphilis? Or is it a case of 
 slight syphilis remaining latent, perhaps localized in the uterus, as 
 has been argued by Frankel? 
 
 What has been demonstrated as true of syphilis is less evident with 
 regard to tuberculosis. There is one fact which seems to be well 
 demonstrated, viz., that individuals of tubercular parentage are 
 often attacked by tuberculosis at a more or less advanced stage. 
 This idea is very old, for Hippocrates admitted the heredity of 
 
CONGENITAL INFECTIONS AND HEREDITY. 595 
 
 phthisis. Recent statistics give a more preci e idea of the trans- 
 mission of the disease in families. The stati tic of Brehmer in the 
 
 sanitarium of (Jorbersdorf and those of Detweiler in Falkei 
 present identical results, 36 per cent, in the former'* Btati tics, which 
 were based upon 1.3,000 patients; 35 per cent, in the latter's, which 
 involved a study of 0000 cases. Hereditary tuberculosis may become 
 manifest at .any age; but, contrary to whal wa once believed, it 
 is not rare during early childhood. We owe to Dr. Landouzy our 
 knowledge of the fact that the victims of tuberculosis during the 
 first two years of life are very numerous. While the fad is incon- 
 testable, its interpretation is difficult. We find ourselves in the 
 presence of two diametrically opposite theories. A has already I een 
 stated, some believe that the bacillus is transmitted, othere thai it is 
 the soil. On the one hand it is asked how i l is possible for the father 
 to transmit tuberculosis to the fetus without contaminating the 
 mother, and how may inherited tuberculosis remain latenl for years 
 and become manifest at an advanced age. On the other hand, the 
 example of syphilis is cited to explain these facts: the occurrences are 
 similar in both cases, and why should we not admit for tubercuh sis 
 what is true with regard to syphilis? Such is the reasoning. U I 
 us now consider the results of clinical observation and experimen- 
 tation. 
 
 There are some observations on record in which children suc- 
 cumbed so rapidly that it is hardly possible to presume a contagion 
 after birth. But these facts may leave some doubt in the mind, since 
 it must be admitted that, in a child predisposed by heredity, acquired 
 tuberculosis may run a rapid course and prove fatal in a few weeks. 
 This would be an evolution similar to that which is observed in 
 animals inoculated in laboratories. The same thing may not be said 
 of those cases in which tubercular lesions were found in stillborn 
 fetuses. Some such facts have been observed in the human species. 
 The first observations are due to Ollendorf, Peter, S. Charrin, and 
 Berti, and belonged to an epoch when Koch's bacillus was yet 
 unknown. More important is the observation of Sabouraud : a child 
 born of a mother suffering from acute miliary tuberculosis succumbed 
 eleven days after birth. At the necropsj' the liver and spleen were 
 found full of tubercular granulations in which the presence of the 
 characteristic bacillus was detected. In an observation reported by 
 Armanni the liver and spleen of a fetus issued of a tubercular mother 
 were inoculated into guinea-pigs and gave tuberculosis to these ani- 
 
596 INFECTIOUS DISEASES. 
 
 mals. In a case reported by Bar and Renon the blood of the umbili- 
 cal cord contained Koch's bacillus. 
 
 Intraplacental transmissibility is, therefore, incontestable ; it is, 
 however, much less frequent in the human species than in animals, 
 especially in the bovine species. Dr. Chauveau has found tubercles 
 several times in fetuses of consumptive cows. By inquiring of 1165 
 Danish veterinarians, Bang found that 32 of them had observed 
 tubercles in newborn calves. While most of these cases may be 
 regarded as doubtful, since no mention is made of the presence of 
 Koch's bacillus, such criticism cannot be addressed to the observa- 
 tions of Johne, De Malvoz, and Brouwier. In fetuses from tubercular 
 cows these authors not only found tubercles but bacilli as well. 
 Misselwitz and Bang have reported similar facts. 
 
 To complete the data of observation it was necessary to resort to 
 experimentation. The results obtained seem to be somewhat con- 
 tradictory. To the positive findings of Landouzy and Martin are 
 opposed negative results of other experimenters. On the other 
 hand, De Renzi, who experimented upon eighteen pregnant guinea- 
 pigs, found tubercles in the fetus five times. In order that there may 
 be contamination, the inoculation must be practised at least thirty- 
 four days before the birth of the } r oung. In several cases these 
 perished in marasmus without becoming tuberculous. Whatever the 
 final solution may be, the results obtained in guinea-pigs should not 
 be applied to man, as there is no proof that the same is true of man. 
 For, by inoculating the white mouse, Gartner found that the tubercle 
 bacillus passed to the fetus, and the same experimenter saw the 
 bacilli infecting the eggs of tubercular canary birds, while the result 
 was negative in hens. 
 
 A last question is whether a tubercular father may beget a tuber- 
 cular child; in other words whether the semen may be the vehicle 
 for the bacilli. As to this point there seems to be no doubt. Even 
 when the genital organs seem to be sound the semen of a tubercular 
 subject may contain the bacilli, as has been demonstrated by the 
 researches of Landouzy and Martin, Weigert, Jani, Bozzolo, and 
 Niepce. Can, however, the bacillus infect the ovum? Baumgarten, 
 who is one of the most ardent advocates of the heredity of tubercu- 
 losis, does not hesitate to answer in the affirmative. In one case, 
 having artificially fecundated a rabbit with the semen of a tubercu- 
 lar rabbit, he detected the bacillus in the ovum. This curious 
 observation does not lead to a firm conclusion, since it is not known 
 
CONGENITAL INFECTIONS AND HEREDITY. :,\u 
 
 what would become of this bacillus or of the ovum the bacillus 
 might not proliferate or the ovum mighl be killed by the microbe, 
 
 and thus uoi, In; developed. If is true that Baumgarten belli ve thai 
 the tissues of the fetus and of the newborn oppose a considerable 
 resistance to the infectious agent, and, to explain tardy hereditary 
 
 tuberculosis, lie contends that (lie bacilli may long sojourn in the 
 lymphatic glands and (he lnuie luarrowwithoul causing any disturb- 
 ance. Later, under the influence of some occasional cause— an 
 inflammation or a traumatism the tissues lose in some degree their 
 vitality and are attacked by the microbes. This conception is sup- 
 ported by the researches of Landouzy and Martin and by the more 
 recent investigations of Birch-Hirschfeld and Schmorl. These 
 authors demonstrated that in fetuses of tubercular mothers the 
 apparently sound organs sometimes contain the specific bacillus. 
 Maffucci's experiments may also be adduced in supporl of tardy 
 inherited tuberculosis. This author, by inoculating various microbes 
 into the eggs of hens, noticed that infection did not become manifest 
 until some time after the eggs were hatched. 
 
 When a fetus of a mammalian is born with tubercular lesions the 
 latter present some interesting peculiarities. Congenital differs from 
 acquired tuberculosis, not in the anatomical characters of the tuber- 
 cles, but in their localization. The liver is the organ most frequently 
 and seriously involved, owing to the fact that the bacilli conveyed 
 through the umbilical vein first colonize in the liver. 
 
 In brief such are the principal facts which may be advanced fro 
 and con in the doctrine of hereditary tuberculosis. In spite of the 
 great number of works published on this subject, the answer to the 
 questions which we had to solve has not yet been given. It seems 
 to be perfectly well demonstrated hy the observations of Landouzy. 
 Queyrat, Hayen, Damaschino, and Lannelongue that tuberculosis is 
 far from rare in young children, and that children born of infected 
 parents are attacked by the disease with alarming frequency. The 
 transmission of the bacilli is also established by a few observations; 
 but facts of this kind, when submitted to severe criticism, as was 
 done by Dr. Kiiss, appear to be altogether exceptional. In the 
 majority of cases parents suffering from tuberculosis transmit to 
 their children nothing more than a predisposition to contract the 
 disease. The children are born with paratubercular alterations, and 
 some of their organs do not attain full development. But they are 
 not tubercu'ous. Schreiber, Hutinel, and Landouzy injected tuber- 
 
598 I N FECTIO US DISEASES. 
 
 culin into children born of tubercular parents without ever obtaining 
 the characteristic reaction. Inheritance of the germ itself is, there- 
 fore, the exception. 
 
 The same conclusions seem to be reached as regards leprosy. 1 
 Danielssen, Bock, and Zambaco attach some importance to the 
 hereditary transmission of this disease. On the other hand, Zambaco 
 admits a tardy heredity and holds congenital leprosy to be alto- 
 gether exceptional. It is well to note, however, that there is not a 
 single case in which bacteriological examination was made. In most 
 instances marriage of leprous individuals leads to sterility, abortion, 
 and non-viability. The children are weak and cachectic and die 
 under age. 
 
 Dystrophies of Infectious Origin. Infection of the parents, and 
 particularly chronic infection of the mother, may impose upon the 
 fetus a defective nutrition. The result is a series of new disorders 
 which may be included under the name of parainfections. In some 
 cases one of the two parents is convalescent from a more or less grave 
 infection at the moment of conception; the product is then a weak- 
 ling, developed imperfectly and predisposed to contract various 
 infections, notably tuberculosis. In syphilis especially numerous 
 examples of parainfectious disorders are observed. Prof. Fournier 
 has made a perfect study of these which we shall sum up in a few 
 words. 
 
 In the first place, there is a fetal cachexia which causes death at 
 a more or less advanced period of gestation. If the fetus does not 
 die it may be born prematurely; at all events it comes into the world 
 as a weakling which develops very slowly. The dystrophy is ex- 
 pressed after birth by incomplete growth; evolution is retarded; 
 the teeth do not appear at the regular periods; the evidences of 
 puberty are delayed; menstruation is not established; the beard is 
 absent. The individual remains imperfectly developed; the genital 
 organs, testicles, and penis are rudimentary; the bones are not suffi- 
 ciently rich in calcium salts; the brain is often atrophied; the intel- 
 ligence is more or less dull. A third group of facts is represented by 
 congenital deformities : syphilis is often found in the parents of indi- 
 viduals suffering from club-foot, spina bifida, harelip, and micro- 
 cephalic and hydrocephalic conditions. Finally, the children of 
 syphilitic parents are predisposed to certain affections of nutritional 
 
 1 Dom Santon. La L6pro.se, Paris, 1901. 
 
CONGENITAL INFECTIONS AND HEREDITY. 599 
 
 order or of infectious origin. Although Parrol erred in considering 
 rickets a manifestation of syphilis, there is no doubt thai thi affec- 
 tion is very frequent among children of syphilitics. [n thi c 
 however, the manifestation is of the paraspecific kind: yphilic hae 
 simply played the r61e of a predisposing cause, tte influence in the 
 appearance of nervous affections, such as Little'i disease, or in the 
 more or less early development of tuberculosis and in the occurrence 
 of meningitis should be interpreted in this manner. 
 
 What we have stated in regard to syphilis may be repeated with 
 reference to tuberculosis. We find the same difficult, incomplete, 
 and slow development in children. Their stature may sometimes be 
 high, but their bones an 1 fragile, their articulations are clumsy, their 
 muscles thin. The skin is thin and transparent; the hair long and 
 silky; the genital organs imperfectly developed; the fingers are Blen- 
 der, and the nails hyportrophied. The thorax is flat and narrow; the 
 lungs small and often emphysematous; the liver is lobulated. Breh- 
 mer and Beneke have noted the weakness of the arterial system, 
 stricture of the aorta and of the pulmonary artery. These children 
 are predisposed to chlorosis and hysteria. Some of them succumb 
 very young, being carried off by convulsions. It is not rare to 
 observe several children die under age, before tuberculosis has clearly 
 manifested itself in the parents. 
 
 Congenital Predisposition and Immunity. 
 
 Heredity accounts for a great number of facts concerning predis- 
 position and immunity. Some families contract certain infectious 
 diseases with the greatest facility and during several generations. 
 Certain families are particularly subject to tuberculosis, diphtheria, 
 scarlatina, or erysipelas. On the other hand, there are immunities 
 of families, communities, and races. It is certain, for example, that 
 the infections imported into countries where they were unknown 
 prove extremely fatal. Such is the case with syphilis and the erup- 
 tive fevers. On the European Continent these diseases are relatively 
 benign, owing to ancestral impregnation. There is created in indi- 
 viduals a certain degree of immunity, or at least resistance, which is 
 transmitted to successive generations. 
 
 This leads us to stud) T the immunity which ma)* be acquired by 
 the fetus in utero. As has been remarked by Vaillard, two events 
 are possible : the mother may contract the disease during gestation, 
 or one of the two parents may be diseased before fecundation. In 
 
600 I MECTIOUS DISEASES. 
 
 the former case the fetus participates in the disease either because 
 the microbes pass through the placenta and invade it or because the 
 placenta forms a perfect filter against the figurate elements and 
 allows only the soluble products to pass. Then disease of the fetus, 
 complete or incomplete, occurs, and the immunity is similar to that 
 established in the adult. In the latter case, on the contrary, the 
 disease having been cured at the moment of conception, there is 
 merely transmission of an acquired character. The immunity con- 
 ferred upon the fetus by a disease of the mother is a result estab- 
 lished b} r numerous observations. As has already been stated, a 
 child born of a mother afflicted by variola, and coming into the world 
 without any appreciable manifestation of the disease, may neverthe- 
 less have acquired immunity against this infection. Vaccinia be- 
 haves in the same manner, at least in certain cases, since the results 
 are quite variable. Burckhard experimented upon eight children; 
 four of them were born of women who had been successfully vac- 
 cinated during gestation. The children proved iimnune, one of them 
 continuing to be so at the end of six months. In two cases re vac- 
 cination gave a doubtful result, and one of the two children born of 
 these women proved refractory. The author likewise observed that 
 one of the two children born of mothers who had been re vaccinated 
 without success at the end of their pregnancy proved refractory. 
 The results obtained by Chambrelent were almost identical. This 
 author vaccinated forty women; he obtained a true vaccinia in the 
 children only seven times. We find quite different figures in Behm/s 
 researches. Out of twenty-nine children observed by this author, 
 only two proved refractory. Finally, Wolff, having successfully 
 vaccinated seventeen women, vaccinated with equal success all the 
 children from one to six days after birth. On the other hand, Lopp 
 observed vaccinal immunity in children, but this immunity did not 
 last more than from six to eighteen months. These contradictory 
 results point to the conclusion that vaccinal immunity, like infection 
 itself, is transmitted only in about half the cases. 
 
 One of the human diseases which has served most for the study 
 of these important questions of general pathology is syphilis. We 
 have already pointed out that a woman bearing a syphilitic fetus, 
 even when she does not contract the disease, becomes immune 
 against the infection; she may with impunity suckle her child which 
 would contaminate a strange nurse. This is what is called Colles' 
 law. This law is confirmed by an experiment of Caspary : A woman 
 
CONGENITAL INFECTIONS AND HEREDITY 601 
 
 fecundated \>y a syphilitic, man, who was apparently cured, aborted 
 at the .sixth month. The mother, who bad presented do specific 
 
 manifestations ;i,i, ;i,iiy lime, consented lo be inoculated, and pri 
 to be immune. In oilier cases the resull is differenl : the fetui does 
 not communicate immunity lo the mother, hul the di ea e itself. 
 This is called syphilis by conception. Diday was one of the fii 
 draw attention to these facts, the Dumber of which at pre en1 is 
 quite considerable. Syphilis by conception runs itt '''Hire like con- 
 genital syphilis. In both instances infection is effected through the 
 blood. The pathogenic agent penetrates directly the circulatory 
 system. Hence, the absence of all primary manifestations. A pr< g- 
 nant woman will then present symptoms of secondary syphilis with- 
 out ever having either chancre or enlargeinenl of the lymphatic 
 glands. 
 
 Profeta has formulated a law similar to that of Colics. If a child 
 born of a syphilitic mother is found in sound condition it has acqu i red 
 immunity against syphilis and does not contract it through the milk 
 or caresses of the mother. This is a result analogous to that observed 
 in other infections, for example, variola. 
 
 Among the experimental diseases anthrax is the one that has been 
 the subject of the most interesting investigations bearing upon these 
 questions. Chauveau, after having inoculated Algerian sheep at the 
 end of gestation, observed that the young born of them presenter] 
 no morbid symptoms when they were inoculated with the bacillus. 
 This is a new illustration of the immunity which may be acquired 
 by the fetus. Anthrax has also been employed to demonstrate ex- 
 perimentally the truth of Colics' law. Lingaard inoculated this 
 disease into fetuses of rabbits while yet in the uterus. The young 
 died, while in most cases the mothers survived. Microscopic exam- 
 ination and cultivation revealed no bacilli in the maternal organisms, 
 and yet the animals had acquired perfect immunity, which still 
 persisted at the end of eight months. The fact is the more interest- 
 ing, as all experimenters are aware how difficult it is to vaccinate 
 the rabbit against anthrax. Moreover, Lingaard established that, in 
 order to confer immunity, the fetus must be inoculated at least 
 thirty-six hours before its expulsion; the other fetuses may become 
 refractory if the inoculated young remain six days in the uterus. 
 In some instances, as in syphilis by conception, the mother contracts 
 anthrax infection; but then placental alterations, through which the 
 passage of the bacilli may be traced, exist. When the mother resists 
 
602 INFEt 'TIO US DISEASES. 
 
 the pathogonic agents have their scat exclusively in the fetal blood- 
 vessels of the placenta. 
 
 On the basis of these experimental facts Chauveau established his 
 famous theory of immunity. After the experiments of Brauell and 
 of Davaine, the placenta was supposed to constitute a perfect filter; 
 immunity was attributed to the transmission of soluble substances 
 produced within the maternal organism under the influence of 
 anthrax. It is at present known that the placenta is in some cases 
 traversed by anthrax bacilli, and, therefore, Chauveau's deductions 
 have been questioned. It has been asked whether congenital immun- 
 ity is not due to the passage of the bacilli which are too small in 
 number to kill the fetus, but sufficient to vaccinate it. To this 
 objection Chauveau answered that the passage of the bacilli through 
 the placenta is an inconstant phenomenon, while in all his experi- 
 ments, fortjr in number, the young had acquired immunity. 
 
 The most important experiments from the standpoint of hereditary 
 transmission of immunity are those in which animals were vaccinated 
 by living microbes or by soluble products more or less long before 
 fecundation. The experiments pursued with symptomatic anthrax 
 had already demonstrated that animals born of mothers vaccinated 
 even some time before fecundation often prove refractory (Arloing, 
 Cornevin, Thomas). 
 
 Studying the transmission of immunity in animals vaccinated 
 against vegetable poisons, such as abrin and ricin, or against tetanus, 
 Ehrlich arrived at the following conclusions: The father does not 
 communicate immunity to his offspring; the mother may impart a 
 transitory immunity which lasts three or four weeks and is not trans- 
 mitted from generation to generation. This is a passive immunity 
 due to intraplacental passage of antitoxin contained in the maternal 
 organism. By studying diphtheria, Wernicke reached identical 
 results. On the other hand, Tizzoni and Centanni, experimenting with 
 tetanus and hydrophobia; Charrin and Gley with the bacillus pyo- 
 cyaneus reached the conclusion that the male is equally apt to 
 transmit immunity. There was, therefore, hereditary transmission 
 of a character acquired by the somatic cells. The question was 
 taken up by Vaillard in a work which may be held as a model of 
 fine experimental criticism. Animals were vaccinated against tet- 
 anus and cholera by means of soluble products and against anthrax 
 by means of living microbes. When a strong immunization was 
 obtained the animals were mated. The young born of a hypervac- 
 
CONGENITAL INFECTIONS \M> HEREDITY. 
 
 ciliated father and a normal mother never presented the sligl 
 degree of resistance. The vaccinated femal< invariably communi- 
 cated to their offspring the immunity which they had acquired. Bui 
 immunity thus transmitted is no1 permanent. Ii may, however, be 
 prolonged by lactation) the mammary secretion furnj h< ome anti- 
 dote to the nursling. This second factor seem to plaj the more 
 important role The researches of Vaillard tend to how, however, 
 that we must not rely too much upon lactation, for milk i active 
 only in certain animal species, the mouse, for example. 
 
 Three theories have been advanced to explain the intrauterine 
 transmission of immunity. Duclaux, Arloing, and especially Charrin 
 and Gley have advanced a cellular theory. According to these 
 authors the cells acquire a certain activity under the influence of 
 vaccination; the cells of generation, influenced like the other cells, 
 impart their mode of life to the being which is developed; the daugh- 
 ter cells continue the physiological activity of their mother cells, 
 and, like these, they are capable of secreting germicidal or anti- 
 toxic substances and exercising phagocytic action. This theory 
 well explains the transmission of immunity by the father; but we 
 know that the view is disputed and rejected by the majority of 
 authors. 
 
 The second theory is that of Ehrlich, according to which the 
 immunity of the fetus is due to the passage through the placenta 
 of antitoxic and germicidal substances from the mother. This the< try 
 would evidently be annihilated if it was demonstrate* 1 some day that 
 the father also may transmit immunity. According to Ehrlich, the 
 mother alone has this power, and the immunity of the fetus is a 
 passive one, analogous to that obtained outside of the uterus by 
 means of serumtherapy. Vaillard admits the passage of the active 
 substances of the serum through the placenta, but, following the 
 ideas of Metchnikoff, lie does not accept the theory that immunity 
 is effected only by means of the fluids of the organism. He remarks 
 that there is not alwaj r s a relation between the state of the fluids 
 and the degree of immunity and believes that the active substances 
 of the mother, passing through the placenta, stimulate the fetal 
 organism, render the cells insensible to intoxication, increase the 
 energy of the phagocytes, and even give rise to the secretion of anti- 
 toxins. This is to extend to the fetus the general theory which is 
 accepted by some authorities concerning immunity. Without dwell- 
 ing upon the discussion, we shall only note that the present tendency 
 
604 INFECTIOUS DISEASES. 
 
 is to attribute immunity, as has already been maintained by Chau- 
 veau, to the intraplaoental passage of soluble substances. Fetal 
 immunity is comparable to that produced by a preventive injection 
 of serum; it is, perhaps, a little more lasting, since the impregnation 
 is longer, but, like all passive immunity, it rapidly disappears. 
 
 Conclusions. Summing up the principal results arrived at, we see 
 that several results are possible. In some cases the microbes produce 
 in the fetus a graver infection than that of the mother. By vac- 
 cinating pregnant sheep we often see the fetus die and expelled by 
 an abortion. The death of the fetus killed by the infection which 
 is resisted by the mother explains a certain number of abortions 
 observed in the human species, for example, in pneumonia, typhoid 
 fever, and syphilis. 
 
 Not infrequently, the fetal disease is similar to that of the adult. 
 Such, in some cases at least, are variola and syphilis. In other 
 instances the fetal affection differs not by its anatomical characters, 
 but by its peculiar localization. Such is the case in congenital tuber- 
 culosis, which invades particularly the liver. It may be said that in 
 almost all fetal infections the liver is most profoundly affected and 
 contains the greatest number of pathogenic agents. This is readily 
 conceivable in view of the fact that this gland is placed like a barrier 
 at the root of the bloodvessels coming from the placenta. There are 
 diseases in which the fetus contains pathogenic microbes without the 
 existence of any appreciable lesions. Thus, as has already been 
 stated, in anthrax the blood does not present the agglutinating char- 
 acter which is so manifest in the adult. In typhoid fever the fetus 
 does not present the alterations in Peyer's patches nor splenic hyper- 
 trophy. 
 
 It is also possible that a child born of an infected mother presents 
 at birth no morbid manifestations, but, after several years, symp- 
 toms of this infection may become manifest. This has been demon- 
 strated in syphilis, and is supposed to be true of tuberculosis. In 
 other instances the infections of the parents may impose upon the 
 fetus an abnormal mode of nutrition which may persist throughout 
 life. Dystrophies, congenital malformations, and predisposition to 
 the most varied infections may result. However, infections of the 
 parents do not always produce disturbances in the children. There 
 are cases in which heredity is not evidenced by any morbid symp- 
 toms. In these instances the child may be influenced by the maternal 
 disease and acquire immunity. This intrauterine vaccination is 
 
CONGENITAL INFECTIONS AND HEREDITY. 606 
 
 inconstant. In a l;i„st category of cases, we place those in tan© 
 which the child comes info flu: world uninfluenced by 'Ik- parental 
 disease. 
 
 Such arc flic principal eventualitie thai may \><- observed. We 
 see that the results are widely variable, from the grave and rapidly 
 fatal infection to the absence of all symptoms, and even of all morbid 
 impregnation. 
 
CHAPTER XXL 
 
 DIAGNOSIS AND PROGNOSIS OF INFECTIOUS DISEASES. 
 
 Various Procedures of Diagnosis. Clinical Procedures. Bacteriological Procedures. 
 Research of Pathogenic Agents by Microscopic Examination and by Cultivation. 
 Inoculations from a Diagnostic Standpoint. Cytological Examination of the Blood, 
 Fluids, and Exudates. The Vesicatory Test. Diagnosis According to Chemical 
 Modifications in Fluids. Research of Agglutination. Modifications in the Urinary 
 Secretion. The Diazo Reaction. Diagnosis by Therapeutics. Diagnosis by Microbic 
 Toxins. Tuberculin and Mallein. Diagnostic Problems. Questions Concerning the 
 Seed and the Soil. Importance of a Complete Diagnosis for Prognosis. The Bases 
 of Prognosis. Personal Statistics: Mortalit}' in 8832 Cases of Infectious Diseases. 
 Influence of Age and Sex upon Mortality. Variation of Gravity According to 
 Various Epidemics. Importance of Etiological Conditions and of Mode of Invasion. 
 Bases of Prognosis during the Stationary Period. Study of the Local Lesion, 
 General Phenomena, and State of the Principal Organs. Importance of Previous 
 Diseases and Lesions for Diagnosis. Prognosis for the Present, for the Future, and 
 for the Descendants. Comparison of Clinical and Bacteriological Methods. 
 
 There are two methods for establishing diagnosis — one, clinical, 
 the other the laboratory method. The clinical method consists in 
 inquiry as to the sensations experienced by the patient, the disturb- 
 ances that may be seen, and the physical signs that may be detected. 
 It is customary, however, to complete the information thus obtained 
 by two more scientific procedures, namely, the determination of the 
 temperature by means of the thermometer, and chemical analysis 
 of the urine. 
 
 The advance in bacteriology and the importance recently acquired 
 by experimental investigations have led to other procedures. It 
 has been asserted that clinical investigations are absolutely inade- 
 quate. It has been said that in order to succeed in determining 
 the nature of a malady it is necessary to resort to methods of 
 precision, to search for bacteria in exudates, secretions, and ex- 
 cretions, and to study the chemical and histological modifications 
 in the organs, tissues and fluids. The consequence is that, in a 
 great number of cases, it is possible to make a diagnosis without 
 examining the patient. It suffices to look for Koch's or Loeffler's 
 bacillus in order to diagnose tuberculosis or diphtheria. It is in no 
 wise pretended to cast doubt upon the service which may be rendered 
 clinicians by laboratory researches, but simply to say that these 
 
DIAGNOSIS AND PROGNOSIS OF INFECTIOUS DI8EA E 607 
 
 two methods are not to be opposed to each other. Some authors 
 have recently taken certain pleasure in pointing to the erroi 
 clinical diagnosis. They seem to be happy to demon trate thai the 
 old methods give but illusive information. For some physicians 
 the diagnosis of diphtheria is absolutely impo ible without cultiva- 
 tion in serum, [t seems to me thai this tendency leads to deplorable 
 conclusions in practical medicine, [tshould not be overlooked thai 
 in many enscs the physician cannot possibly resorl to new methods. 
 A practitioner in a country place, for example, far from scientific 
 centres, can hardly have the facilities for making cultures. If it i- 
 a case of acute infection, and if , guided by new ideas, he sends the 
 suspicious exudates to the aearesl faculty, the chancee are thai he 
 will receive an answer when the evolution of the disease ie al an 
 end — i. e., when the patient has recovered or is dead. This does 
 not mean that scientific datn are to be rejected. Those who are 
 practising in cities possessing laboratories, and especially those who 
 attend in hospitals, must resort to modern methods of investigation. 
 This, however, should not be done with the idea of opposing the 
 results furnished by cultivation to information given by clinical 
 observation — to show the superiority of the former and the un- 
 certainty of the latter. He who can combine observation and 
 experimentation must decide what modifications must be introduced 
 into nosological classification and give greater precision to simple 
 observations. Bacteriology must be resorted to, not to show the 
 insufficiency of clinical observation, but as a means of more closely 
 approaching the truth. Those who have a hospital with a laboratory 
 at their disposal must compare the results furnished by differ. -n? 
 procedures of exploration, and, far from bringing out their antag- 
 onisms, seek to harmonize them. It seems to me that we must not 
 as yet ask too much of bacteriological data. "We shall presently 
 show that they sometimes furnish indications less certain than those 
 yielded by simpler procedures of exploration. 
 
 Search for Pathogenic Agents by Microscopic Examination and 
 Cultivation. The means now at our disposal for making a scientific 
 diagnosis maybe divided into three groups: the search for microbes, 
 the study of modifications in cells and fluids, and the specific action 
 of certain toxins. 
 
 The search for microbes is made by microscopic examination, 
 cultivation, and inoculation into animals. Microscopic examination 
 is applied to secretions, dejections, and inflammatory foci: more 
 
608 IXFECTIOUS DISEASES. 
 
 rarely to the blood and the interstitial fluids of organs. It renders 
 very remarkable service in determining the nature of an inflam- 
 matory lesion, an effusion into a serous cavity, an abscess, and a 
 gangrenous focus. When a focus does not communicate with the 
 exterior — i. c, when it has not been invaded by common bacteria 
 from without, one may be nearly certain that when a microbe is 
 found it is the agent of the morbid process. At any rate the pro- 
 cedure is very simple, and the harmlessness of exploratory puncture 
 justifies this sort of investigation in most cases. On the contrary, 
 when the morbid focus is not closed, it generally contains several 
 microbic species. Hence, interpretation becomes far more difficult. 
 In some cases a clearly differentiated specific bacterium is found 
 and is responsible for the morbid phenomena. Such, for instance, 
 is the case when actinomyces are detected in a purulent fluid or 
 the tubercle bacillus in sputa. The result has no importance, 
 however, except when it is positive. The absence of Koch's bacillus 
 in a sputum does not at all imply the absence of tuberculosis. Never- 
 theless, the scientific character of these researches gives an exagger- 
 ated importance to the results obtained. The fact that the bacilli 
 are absent from the sputum when the morbid foci are closed is too 
 easily overlooked. Errors inherent in defects of technical methods 
 must also be remembered. Examination for bacilli, simple as it is, 
 none the less requires a certain amount of experience. I saw a 
 patient with syphilitic antecedents suffering from manifest pulmo- 
 nary tuberculosis. The physical signs left no doubt whatever as 
 to the diagnosis. He had been given for several weeks, and to his 
 detriment, large doses of potassium iodide. His physician, a very 
 able man, who had instituted the treatment, had based it upon 
 the absence of Koch's bacillus in the expectorations. There had 
 certainly been some technical error, for when I examined the case I 
 found the sputa nummular and swarming with tubercle bacilli. 
 Such errors are not rare. I could cite several examples of a 
 similar character. 
 
 When the bacilli are present, certainty is established. When, 
 however, the parasites are few in number, doubt still remains. We 
 know that Koch's bacillus may vegetate upon certain mucous mem- 
 branes as an inoffensive parasite. Its presence does not necessarily 
 imply the existence of a tubercular lesion. Such is the case with 
 the tonsil, which often contains bacilli, but is seldom affected by 
 them. The difficulties are far more considerable when less clearly 
 
DIAGNOSIS AND PROGNOSIS OF TNFECTI0U8 DISEASES. 609 
 
 specified bacteria are Looked for. For example, expectoration are 
 examined and streptococcus, pneumococcui . Friedlander' bacilli] . 
 
 tetragenes, ;i,ihI various spirilla are found. Whal righl have we to 
 conclude that such and such a microbe, to the exclusion of other . 
 is the cause of the morbid manifestations? [f one pecie pre 
 dominates, the probabilities are thai ii is tin- pathogenic agent. 
 There is, however, no absolute certainty, and we have already -ecu. 
 with reference to anginas, how difficull interpretation is in the 
 majority of cases. Thus, in chancriform tonsillitis an a sociation oi 
 spirilla and fusiforin bacilli, which are of greal diagnostic value, are 
 found The same association, however, may be me1 with in other 
 clinical types and even in syphilis. Such was manifestly the case 
 with secondary tonsillar lesions of very difficull diagno 
 
 When bacteria are found irregularly disseminated ;i decision Lb 
 impossible. Hence, for the diagnosis of anginas, another procedure 
 is resorted to — cultivation. The point to he settled is, in general, 
 whether an angina is or is not diphtheritic in nature. A- Loeffler's 
 bacillus rapidly vegetates in gelatine serum and develops in this 
 medium sooner than other bacteria, the method becomes very 
 simple. A particle of the suspicious exudate is spread upon gelatine 
 serum and is placed in the incubator. At the end of twelve hours 
 the bacillus of Loeffler, if present, produces colonies. This mode of 
 action is usually not objectionable. It must be noted, however, 
 that in certain cases the development of the bacillus is more tardy. 
 It sometimes takes twenty-four or thirty-six hours. On the other 
 hand, while there is no doubt when the colonies are abundant and 
 rich in bacilli, it may still be a question whether an angina should 
 necessarily be regarded as diphtheritic simply because Loeffler's 
 bacillus has been detected by serum culture. If another medium 
 had been employed, a different result would have been obtained. 
 If, for instance, the cultivation had been made in bouillon the 
 streptococcus might be present and Loeffler's bacillus absent. What 
 right, then, have we to conclude that the angina was diphtheritic? 
 Why should the results furnished by cultivation in one medium be 
 more valuable than those obtained in another? Why prefer serum 
 to agar-agar or to bouillon? Why accept Loeffler's bacillus and 
 ignore the streptococcus, which is just as harmful? 
 
 An attempt has been made to avoid the difficulty by the admission 
 of a hybrid form having particular clinical characters, which has 
 been designated strepto-diphtheria. This reasoning is open to 
 
 39 
 
(310 INFECTIOUS DISEASES. 
 
 criticism. In order to admit this form the development of two 
 bacteria in blood serum is required. It is hard to conceive why 
 an important role is attributed to the streptococcus solely on the 
 ground that it develops in serum. Its multiplication in this medium 
 does not at all prove its virulence. Even though we admit that the 1 
 procedure is exact, other difficulties arise. What conclusion is to 
 be drawn in those cases in which cultivation gives only scanty 
 colonies of the diphtheria bacillus? It is known that this bacillus 
 quite often vegetates in the normal mouth. When it is encountered 
 in culture it may be asked whether or not we have to deal with an 
 inoffensive parasite. Moreover, although this bacillus is readily 
 recognized, there is a short bacillus, the nature of which is in no 
 wise determined as yet, which is considered by some as a variety 
 of the diphtheritic bacillus, and by others as a particular microbe. 
 In this case, bacteriological diagnosis is indecisive. 
 
 Referring to the results which we have described in treating of 
 microbic associations (p. 145), it may be noted that in thirty-one 
 cases of anginas studied comparatively by direct examination and 
 by cultivation in agar-agar and serum, we constantly found Loefner's 
 bacillus in the last-named medium, while we detected it in only half 
 of the cases by direct examination or by cultivation in agar-agar. 
 Moreover, in these thirty-one patients the exudate contained strepto- 
 cocci visible by direct examination nine times; cultivation in agar- 
 agar revealed them sixteen times, and cultivation in serum three 
 times only*. Still, in one case in which the streptococcus developed 
 in serum, agar-agar showed only the tetragenus. 
 
 These reflections are by no means intended to discredit the results 
 furnished by bacteriology. They are intended only to call attention 
 to the disposition of many authors to attribute an absolute value to 
 the data of cultivation. A vast amount of research is yet required 
 in order to base a description of anginas upon a parallel study of 
 their clinical aspect and experimental results. I have dwelt upon 
 anginas because these are the affections the study of which has 
 most profited by modern bacteriological investigations. We possess 
 no selective medium analogous to blood serum for the other patho- 
 genic bacteria. The preparation of media for the cultivation of 
 specific bacteria in the midst of common parasites has not given 
 gratifying results. 
 
 The employment of peptone-water is useful in the diagnosis of 
 cholera, but the detection of Eberth's bacillus in fecal matters is 
 
DIAGNOSIS AND PBOONOSIS OF INFECTIOUS DISEASES. r,\\ 
 
 far more difficult. Eisner's formula does not seem to respond to 
 the purpose in view . 
 
 Bacteriological examination ii of con iderable intere I in connection 
 with sexual diseases. Examination for the gonococcu i daily 
 practised and serves bo establish the diagnosis of gonorrhea 
 well to remark, however, thai recently there have been found in 
 the suppurations of the genital organs anaerobic microbes which 
 have nothing in common with the gonococcus, bu1 ii i very difficult 
 to recognize them by a simple microscopic examination. 
 
 When the process is one of common suppuration two casee are 
 possible: The focus ui;iy be closed or open. When ii i closed a 
 puncture is made into it and a specimen of the Quid i- submitted 
 to microscopic examination and to cultivation. The data ob- 
 tained have undeniable value, provided the resulte of direcl 
 animation be carefully compared with those furnished by cultivation. 
 If by both of these procedures a single species is found, certainty 
 is almost absolute, but not complete, since it is possible that the 
 true pathogenic agent may be unrecognizable by our present methods 
 of staining and cultivation. This possibility is becoming less and 
 less as bacteriology advances, and the result is perfect in most cases. 
 The result is also satisfactory when several specie- of microbes are 
 found. If, however, a great number of different bacteria are re- 
 vealed by microscopic examination, and if cultivation shows only 
 one or two, the difficulties are the same as in the case of angina. 
 Such is the case with gangrenous foci. Anaerobic cultures have 
 greatly aided the study of this morbid process, but by a natural 
 reaction too much importance has been attributed to anaerobics. 
 In most cases putrefactive microbes do no more than complete 
 the work already begun. The}' putrefy tissues altered by other 
 microbes, and notably by aerobics. Moreover, we must remember 
 that the latter may of themselves produce certain gangrenes which 
 are sometimes of benign character. 
 
 When an open focus is examined the results are very clear it only 
 one species of microbe is found. If several species are detected. 
 the difficulties of interpretation are the same as in the case of angina. 
 In some cases, however, the presence of certain morphological 
 elements is of paramount importance. Thus, whether the lesion be 
 open or closed, the presence of yellow grains resembling flowers of 
 sulphur establishes the diagnosis of actinomycosis. 
 
 The associated microbes are then of little consequence : the nature 
 
612 INFECTIOUS DISEASES. 
 
 of the lesion is well determined, and furnishes accurate indications 
 for treatment. 
 
 The microbe may likewise be looked for in fluids, secretions, or 
 natural excretions, or even in the organs. In this connection the 
 blood, urine, fecal matters, and cerebrospinal fluid are examined. 
 Capillary punctures into the viscera are practised, particularly into 
 the spleen. By microscopic examination of the blood it is possible 
 to recognize certain absolutely characteristic specific parasites, such 
 as the spirilla of recurrent fever and the hematozoon of malaria. 
 The search for the hematozoon is not always easy, but when it is 
 positive the result has considerable importance from a practical 
 standpoint. It permits elimination of symptomatic intermittent 
 fevers and gives a solid basis for treatment. As we have already 
 stated, special corpuscles are found in the blood of variola patients 
 by simple microscopic examination. These corpuscles are particu- 
 larly numerous in the hemorrhagic form. In the suppurative forms 
 they are seen at the beginning of the disease, at the period when 
 diagnosis is difficult. In most bacterial diseases microscopic 
 examination reveals no bacteria or reveals them only at a more 
 advanced stage when death is approaching. In the case of anthrax 
 and of septicemias the blood is not invaded until death is near. 
 It is not so, however, with methods of cultivation, which may give 
 positive results at a less advanced period of an infection, provided 
 cultivations be practised on a large scale. According to the pro- 
 cedure employed by Davaine, 1 c.c. of blood must be taken from 
 a vein and placed in appropriate media. 
 
 Examination for microbes in the urine is seldom practised. It 
 is a difficult procedure. If a simple microscopic examination is to 
 be made, the urine must be centrifuged and the deposit examined. 
 If cultures are to be made, the urine must be drawn by aseptic 
 catheterization, which requires a great deal of practical experience 
 in order not to be misled by accidental contamination. The study 
 of fecal matters is not less difficult. In certain cases, however, 
 microscopic examination renders service by showing a common 
 microbe predominating or by revealing a .specific agent. Thus, the 
 tubercle bacillus may be found in the excrements, and this fact is 
 of great importance, since bacilli which have been ingested do not 
 pass into the fecal matters. The presence of Koch's bacillus in the 
 feces, then, permits affirmation of the existence of intestinal tuber- 
 culosis. In dysentery examination of the dejecta it is likewise 
 
DIAGNOSIS AND PROGNOSIS OF INFECTIOUS DISEASES. 613 
 
 necessary, for it enables us to determine whether or nol the ci 
 
 one of amebic dysentery. 
 
 In recent years the search for microbe is Hi" cerebral spinal 
 fluid has acquired great importance. Lumbar puncture being an 
 inoffensive operation, we easily conceive how serviceable tlii- method 
 
 of exploration may prove The search for microbe m the 0T( 
 requires greater precautions. Puncture of the liver, once quite 
 frequently practised for the diagnosis "I' typhoid fever us rather 
 an uncertain method, .■mil '•.■m hardly enter into '•uncut practice. 
 
 Inoculations from a Diagnostic Standpoint. The difficulty oi 
 attributing morbid manifestations i<> one form of pathogenic bacteria 
 rather than i<> another has suggested the method of inoculation into 
 animals. It was even hoped that this method would enable us to give 
 a positive prognosis. It was thought that a relation existed between 
 the evolution observed in man and the effects produced by experi- 
 mental inoculation. Such a relation undoubtedly existfi in a certain 
 number of cases, but not in all. As regards the streptococcus 
 particularly, the results are absolutely deceiving. Cultures pre- 
 pared with blood taken immediately after death have often been 
 injected in large doses without producing the slightest disturbance. 
 Among observations which I have collected, the following may be 
 cited. 1. Pulmonary gangrene ending fatally; the fluid contained 
 in the lungs presented especially streptococci. When directly 
 inoculated into the veins of a rabbit in the dose of 1 cubic centimetre, 
 it produced a chronic disease characterized by paraplegia and reten- 
 tion of urine, ending fatally at the end of two months. The cultures 
 injected into the veins in the dose of 5 c.c. gave rise to no disorder. 
 2. Streptococcus obtained from a newborn which had succumbed to 
 erysipelas of the navel; the first culture, when injected into two 
 rabbits in the dose of 5 c.c, caused no morbid manifestations. 3. 
 Streptococcus obtained from an aged man dead of erysipelas ; same 
 experiments, same results. 4. Streptococcus obtained from dead 
 of puerperal fever; same experiments, same results. These few 
 facts once more demonstrate how difficult it is to apply to man 
 conclusions drawn from experiments performed upon animals, and 
 how uncertain is determination of virulence, at least in the case of 
 the streptococcus. 
 
 It is true that a great number of observations have been published 
 which seem to establish that, in cases of angina, inoculation into 
 animals may furnish interesting data. For example, when we find 
 
614 INFECTIOUS DISEASES. 
 
 a bacillus presenting the characters of the diphtheria bacillus, the 
 nature of which is not quite well determined, it is incontestable that 
 inoculation may elucidate the problem. Thus, at the necropsy of 
 a diphtheritic case, I found an hepatic abscess containing a bacillus 
 analogous to Loeffler's. In order to establish a more certain diag- 
 nosis, I inoculated two guinea-pigs. One was kept as control and 
 rapidly succumbed; the other, which received at the same time 
 antidiphtheritic serum, remained in good health. In this instance 
 the demonstration is unassailable. 
 
 AYhile inoculation solves the problem when a single species of 
 bacterium is detected in a focus, it may furnish doubtful data when 
 several species of microbes are encountered. If one of these is 
 inoculated and found to be pathogenic, it cannot be concluded that 
 it was the cause of the accidents, for the agents unconsidered were 
 perhaps just as virulent. Therefore, in order to form a conclusion, 
 it is necessary to inoculate all the microbes isolated — a task repre- 
 senting considerable labor — and still the result would be disputable, 
 for the reason that it is possible that the specific microbe will not 
 develop in the particular medium employed, either because this 
 medium is not favorable for it or because the other bacteria prevent 
 its multiplication. I recognize, however, that inoculation into 
 animals may be of very great service. For example, a polymicrobic 
 culture is obtained. By injecting it into an animal we may see a 
 bacterium predominate, and it will then be possible to obtain a pure 
 culture after one or two passages through animals. Of course, it 
 would not yet be safe to draw an absolute conclusion. Nothing 
 proves that the microbe which is the most harmful for the animal 
 was the one most harmful for man. Here, therefore, is a method 
 that renders remarkable service to the experimenter rather than to 
 the clinician. Confining ourselves to the domain of clinical diagnosis, 
 we find various infections the diagnosis of which may be facilitated 
 by inoculation. These are the pneumococcic infections, anthrax, 
 glanders, tuberculosis, hydrophobia, and, less frequently, gaseous 
 gangrene and tetanus. 
 
 When the pneumococcic nature of a lesion is suspected, an inocu- 
 lation is made into the mouse. The animal succumbs within twenty- 
 four or forty-eight hours, and examination of the blood shows 
 characteristic capsulated diplocojcci. It is well to remember, how- 
 ever, that this bacterium is often encountered in the saliva of healthy 
 individuals. The positive result of this inoculation cannot, there- 
 
DIAGNOSIS AND PROGNOSIS OF INFECTIOUS DI8EA8E8. 616 
 
 fore, lead to an unquestionable conclusion. When ;i lesion i 
 pected to be of anthrax, diagnosis may be a matter of difficulty, for 
 the reason thai malignanl pustule often contains very few bacteria, 
 and, therefore, experimental inoculation i negative. 
 
 [n a case in which the diagnosis was difficull and which terminated 
 in recovery I inoculated four guinea-pigs with the serum of the 
 vesicles. ( >ne of these animals died of anthrax, thus demonstrating 
 the nature of the lesion which, without inoculation, mighl have Ween 
 interpreted in a differenl manner. 
 
 The diagnosis of glanders often presents greal difficulties. An 
 experimental method has, therefore, been long looked for. The ase 
 first served for purposes of experimentation. When this animal is 
 employed (lie operation is performed in the following manner: 
 After shaving the forehead, cutaneous scarifications are made, and 
 then the suspicious pus is rubbed upon them. From the tenth to 
 the fourteenth day the general phenomena appear, and the animal 
 soon dies of bronchopneumonia. The necropsy reveals glanders 
 granulations in the viscera. Instead of the ass the dog may be 
 employed. The same method is resorted to, and four or five day- 
 after inoculation a glanders ulcer appears which subsequently heals. 
 Christot and Kiener proposed a simpler procedure. They advised 
 inoculation into the guinea-pig. The animal died in eight or ten 
 days with characteristic lesions. The best method is that of Straus. 
 The suspicious pus is injected into the peritoneum of a male guinea- 
 pig. At the end of forty-eight hours a testicular vaginalitis develops. 
 The skin of the scrotum becomes red and the two layers of the tunica 
 vaginalis adhere by a purulent exudate. The testicle and epididymis 
 are seldom involved. This method is good, but not perfect. The 
 pus may contain various bacteria capable of producing a fatal peri- 
 toneal septicemia. Hence, it is advisable to inoculate two guinea- 
 pigs, one beneath the skin, the other into the peritoneum. On the 
 other hand, various pyogenic microbes behave like the bacillus of 
 glanders (Nocard). The result of inoculation must, therefore, be 
 controlled by bacteriological examination and cultivation. 
 
 Examination for the tubercle bacillus is so easy that inoculation 
 is seldom necessary. In cases of local tuberculosis, however, and 
 in those pulmonary lesions in which favorable evolution seems to 
 remove all suspicions as to the tubercular nature of the process, as 
 well as in pleuritic effusions, the bacilli are so few in number that 
 there is great danger of not detecting them by microscopic exami- 
 
(316 ISFECTIO US DISEA SES. 
 
 nation. In such instances inoculation is most serviceable. The 
 inoculation must be practised upon the guinea-pig, which is the 
 animal most sensitive to tuberculosis. Survival is very long; it 
 often exceeds rive or six weeks, and at times the animal may live 
 for several months or even a year. The early development of 
 adenopathies is significant. Six or eight days after inoculation the 
 lymphatic glands corresponding to the point of inoculation become 
 congested, and other glands are later involved. These multiple and 
 progressive glandular affections are absolutely characteristic. The 
 method may, therefore, be of use, notably in cases of serous pleurisy. 
 As is known, the diagnosis of hydrophobia is a matter of great 
 difficulty. Even at the necropsy a retrospective diagnosis cannot 
 be made. No characteristic lesion is found in the viscera and tissues. 
 This fact is of considerable importance in practice. When an 
 individual is bitten by a rabid dog it is too often the custom to kill 
 the animal and then send the cadaver to a veterinary physician for 
 necropsy. Great diagnostic value was formerly attached to the 
 presence of foreign bodies in the stomach of rabid dogs. These 
 animals bite and swallow anything they encounter. Hence, sub- 
 stances which are not usually among the contents of this organ, 
 such as pieces of wood, straw, earth and gravel, are found in their 
 stomachs. It has been demonstrated, however, that these findings 
 are of no diagnostic importance. Such substances are likewise 
 found in non-hydrophobic dogs. In view of the investigations of 
 Van Gehuchten, histological examination may, perhaps, give better 
 results. But such researches are delicate and require accurate 
 knowledge of histology. For the time being the study of symptoms 
 seems to me to be of greater importance. Hence, this practical 
 conclusion: No dog which has bitten a person should be killed: 
 but it should be confined and carefully observed. This is the only 
 means of learning at the end of two or three days whether it is 
 hydrophobic or not. Moreover, the circumstances under which the 
 biting occurs furnishes a presumptive basis. It may be said that a 
 dog which bites without provocation and without any appreciable 
 cause is generally rabid. If the animal has been killed, the only 
 means of obtaining conclusive information is inoculation. This 
 operation is generally performed upon the rabbit. The emulsion 
 obtained with the medulla is injected beneath the dura mater. The 
 operation is extremely simple: The animal being firmly bound, 
 and, if necessary anesthetized, an incision is made into the skin. 
 
DIAGNOSIS AND PB0ON0SI8 OF INFECTIOUS DISEASES, 617 
 
 The cranium is opened by means of a smal trepan, avoiding the 
 upper Longitudinal sinus. The hemorrhage produced by incision ol 
 the bone is generally quickly arrested. Then, by meane oi a curved 
 canula adjusted to a Pravaz syringe, the dura mater i punctured 
 and a few drops of the emulsion are injected beneath this membrane. 
 The canula is withdrawn, the wound sutured and covered with 
 iodoform collodion. Under these conditions the animal contract* 
 hydrophobia after a period of incubation varying from twelve to 
 fifteen days. T<> ensure the production of hydrophobia, il U oo1 
 
 absolutely neeess:ir\ lo resorl I" llie procedure jusl described. 
 
 Introduction of the virus into the anterior chamber of the eye gives 
 
 nearly as certain results. The same is true when the inoculation i- 
 made into any nerve whatever, for example, into a peripheral nerve. 
 Galtier, l)i Vesica and Zagari have shown thai the sciatic nerve 
 offers a very reliable route of introduction. Finally, when .1 con- 
 tused wound contaminated by foreign bodies or earth becomes the 
 starting point of morbid manifestations, the inoculation into a 
 guinea-pig of the fluid discharged from the lesion or, still better, of a 
 particle obtained by scraping, may reveal, within forty-eighl hour.-. 
 the presence of the microbe of gaseous gangrene or of tetanus. 
 
 Cytologic Examination. A new method of diagnosis consist- in 
 searching for certain reactions produced in the organism by patho- 
 genic agents. The attention of observers was first attracted by the 
 blood. In fact, from the start of infections this fluid undergoes 
 profound modifications, some of which bear upon the cellular elements 
 and may be detected under the microscope. We have already stated 
 that the variations in the white blood corpuscles enable us to follow 
 the evolution of infections, and at times to foretell their course and 
 announce relapses. These observations less frequently serve the 
 purposes of diagnosis. Nevertheless, the researches of Courment 
 and Montagard and those pursued at the same time by Dr. "Weil 
 in our wards show that the leucocytic formula of the blood presents 
 particular characters in variola. The results are so clear that we 
 often resort to this procedure in order to settle diagnostic difficulties. 
 It must be remembered, however, that varicella and variola produce 
 analogous modifications in the blood. The method mostly serves 
 to differentiate variola from other eruptive fevers and various 
 pyogenic infections which simulate it. 
 
 The examination of the cells may be made not only in the blood 
 but in other fluids and exudates. Examination of the cerebro- 
 
618 / SFECTIO US DISEA SES. 
 
 spinal fluid and of effusions produced in various serous membranes 
 has led to a cyto-diagnosis the importance of which lias been well 
 shown by Widal and Ravaut. 
 
 In cases of primary tuberculosis of the pleura pleuritic effusion is 
 remarkable for the almost exclusive presence of small lymphocytes. 
 In individuals afflicted with cancerous or ulcerating lesions of the 
 lungs, or hydropneumothorax, numerous altered polynuclears are 
 found, while in mechanical pleurisy the endothelial cells of the 
 pleura predominate. In the case of streptococcic pleurisy neutro- 
 philic polynuclears are almost exclusively present. In pneumo- 
 coccic pleurisy the greater part of the cells is represented by poly- 
 nuclears and large mononuclear cells mixed with red blood corpuscles 
 and a few lymphocytes. 
 
 The Vesicatory Test. These researches are applicable only to 
 certain special cases. Hence, it seemed to me to be interesting to 
 determine the cytologic formula of effusions which may be produced 
 in man by the application of vesicatories. The examinations which 
 we made with Dr. Josue 1 established that the vesicle produced by a 
 vesicatory holds in suspension a fairly large number of cells. In 
 the normal man a strong proportion of polynuclear eosinophiles is 
 found. In individuals suffering from an infectious disease these 
 cells are less numerous or altogether absent. They reappear if the 
 organism overcomes the infection. The vesicatory test thus furnishes 
 valuable indications regarding the intensity of the toxi-infectious 
 impregnation of the organism and the mode of reaction of the 
 hematopoietic organs. It is readily conceivable what advantage 
 may be drawn from such information from a diagnostic and especially 
 prognostic standpoint. The difference in the results obtained in the 
 healthy man and in the sick must depend upon the action exercised 
 by microbic toxins upon the hematopoietic organs, and notably upon 
 the bone-marrow. Under the influence of these poisons the bone- 
 marrow gives rise to neutrophilic polynuclears. On the contrary, 
 it cannot furnish eosinophiles. Ehrlich has well shown this sort of 
 antagonism which exists between the infectious process and eosino- 
 philia. The application of a vesicatory stimulates the production 
 of eosinophiles, and the examination of the fluid shows in what 
 measure the bone-marrow is capable of producing these elements. 
 The vesicatory test thus enables us to determine the intensity of 
 
 1 Roger and Josue\ L'epreuve du vesicatoire. Soc. m6d. des hopitaux, May 3, 1901 . 
 
DIAGNOSIS AND PROGNOSIS OF INFECTIOUS DISEASES. 619 
 
 the action of toxins upon the hematopoietic organs. By this method 
 we may judge to whal extenl the function of the e organ i- dimin- 
 ished under the influence of the toxic element. 
 
 Apart from the eosinophilic polynuclear there are found in the 
 vesicle neutrophilic polynuclears and large and small mononuclears. 
 It is not rare to find in the preparations a certain dumber of large 
 mononuclear elements containing granulations. These are myelo- 
 cytes. Tliis fact is interesting, since no such cells are commonly 
 found in the Mood or in pathological exudates. They generally 
 remain in the bone-marrow, where they give rise to white globules 
 with polymorphous nuclei or polynuclears. The presence of myelo- 
 cytes [troves that the vesicatory produces a very profound effecl 
 upon the hematopoietic organs. Besides the cells above described, 
 all of which are similar to those circulating in the normal or patho- 
 logical blood, particular elements are found in the fluid produced by 
 the vesicatory. These are cells provided with a thin layer of proto- 
 plasm which is colored brownish -yellow by triacid and rose by eosin. 
 Their nucleus, which is round or oval, is stained green by triacid and 
 pale violet by hematoxylin, but is not clearly defined. Unable, as 
 yet, to decide the nature and origin of these elements, we shall 
 designate them "vesicatory cells.'' Our researches were made upon 
 two normal individuals and twenty-seven patients, eleven of the 
 latter suffering from pulmonary tuberculosis, and three seemingly 
 from tubercular pleurisy. The technique employed was very simple. 
 Twelve hours after th ; application of a vesicatory of four or five 
 square centimetres, when the bulla was well formed, the fluid was 
 taken, centrifuged, and decanted, and the sediment spread upon 
 slides and dried over the flame. Most of the preparations fixed by 
 heat at 230° F. (110° C.) were stained with Ehrlich's triacid solution 
 or thionin. A few were treated with alcohol-ether and stained with 
 eosin-hematoxylin. The preparations obtained by the triacid stain 
 are the clearest. 
 
 In the two normal individuals we found a very large proportion 
 
 of eosinophils. In no pathological case did we find such a great 
 
 number. A count of the various species of cells gave the following 
 
 figures : 
 
 i. ii. 
 
 Neutrophilic polynuclears .... 65.0 per cent. 77. S per cent. 
 
 Eosinophilic polynuclears .... 25.5 " " 19.2 
 
 Large mononuclears 1.0 " "i 
 
 3 • ■ " 
 Small mononuclears S.O " "J 
 
 Vesicatorv cells 0.5 " " 0.0 
 
620 IXFECTIO US DISEA SES. 
 
 The vesicatory test leads to altogether different results in tuber- 
 culous subjects. In cases of common chronic tuberculosis a very 
 great number of polynuclears are found. These reach or exceed 
 90 to 95 per cent. On the other hand, the eosinophiles are very 
 rare and in most cases are absent. The proportion of large and 
 small mononuclears is quite variable according to the case. That 
 of the vesicatory cells varies between 0.5 and 3 per cent. In one 
 tubercular case (Obs. XL) the number of the eosinophiles was rela- 
 tively large. It amounted to 3.2 per cent. This case was not an 
 exception to the rule, for it was a man suffering from a peritoneal 
 localization and from pulmonary lesions tending toward sclerosis. 
 The relatively high percentage of eosionphiles indicated the favor- 
 able course of the disease toward recovery. 
 
 Furthermore, we have noticed that the cells present a special 
 aspect in tuberculous individuals. They are swollen and much 
 larger than in normal subjects. This particular state of the cellular 
 elements is not absolutely peculiar to tuberculosis, but it is far more 
 pronounced in this infection than in others. Hence, when it is 
 manifest, it may lead to the detection of a latent tuberculosis. 
 This is precisely what happened in one of our cases (Obs. XII.). 
 Having applied a vesicatory to a man whom we considered to be 
 in normal condition, we were surprised to find in the fluid a low 
 percentage of eosinophiles as compared to the normal ratio, and a 
 sufficiently great number of swollen cells. Minute examination of 
 the respiratory organs enabled us to recognize slight but incontest- 
 able lesions, which, until then, had produced no functional disturb- 
 ance. Percussion revealed dulness under the right clavicle and in 
 the left supraspinous region. In the same regions inspiration was 
 harsh and attended by a few dry rales and pleuritic frictions. The 
 relatively high percentage of eosinophiles (7.82 per cent) indicated 
 that the constitution was vigorous — a fact quite in harmony with 
 the results of clinical examination. It may be added that the 
 vesicatory test gives the most valuable information in the beginning 
 of tuberculosis and enables us to appreciate the degree of resistance 
 of the individual and his chances of recovery. 
 
 The number of eosinophiles was still larger in two cases of acute 
 serofibrinous pleurisy. This affection may be considered as a local 
 tuberculosis of the pleura tending toward recovery. It would, 
 therefore, be natural to expect to find a formula expressing the 
 resistance of the organism. This is precisely what was found in 
 
DIAGNOSIS AND PROGNOSIS OF XNFE0TI0U8 DISEASES 821 
 
 Observations XIII. and XIV. [n a third case, however (Ob XV. . 
 the formula was different. This wa a case of pleurisy which wb 
 being cured, but a day before we applied Wk- ve\ icatory the patienl 
 was attacked by intense gastrointestinal disorder with hypo- 
 thermia 95.7° V. (MA C). This superadded affection ufficed t<, 
 completely modify the cellular formula of the vesicatory fluid. Thk 
 observation established the extreme sensitivenest of the procedure 
 and shows with what rapidity pathologic influences affeel the organic 
 reactions. 
 
 TUBERCULOSIS. 
 
 
 I. 
 
 II. 
 
 III. 
 
 IV. 
 
 V. 
 
 1 
 VI. 
 
 VII. 
 
 VIII. 
 
 IX. 
 
 X. 
 
 XI. 
 
 XII. 
 
 I'l 
 XIII 
 
 
 
 XIV. 
 
 XV. 
 
 Neutrophilic | 
 polynuclears j 
 
 9.26 
 
 85.5 
 
 95.0 
 
 96.0 91.6 98.6 
 
 95.00 
 
 89.25 
 
 62 
 
 90.0 
 
 92.6 
 
 74.10 
 
 71. 1 
 
 06.8 !'l." 
 
 Eosinophilic ) 
 polynuclears j 
 
 
 
 
 
 0.8 
 
 
 
 
 
 
 
 
 
 
 
 0.8 
 
 3.2 
 
 7.32 
 
 18.7 
 
 17.0 
 
 1.2 
 
 Large mononuclears 
 
 3.4 
 
 9.0 
 
 1.0 
 
 2.8 
 
 0.8 
 
 1.00 
 
 5.75 
 
 21 
 
 2.0 
 
 •j. 6 
 
 3.64 
 
 
 n.:. 
 
 5.0 
 
 Small mononuclears 
 
 2.8 
 
 
 
 1.8 
 
 1.2 4.8 
 
 
 
 1.75 
 
 
 
 10 
 
 5.2 
 
 0.4 
 
 13.14 
 
 - 
 
 1.5 
 
 
 
 Neutrophilic mye- 1 
 locytes j 
 
 0.8 
 
 3.5 
 
 0.3 
 
 
 
 0.8 
 
 0.6 
 
 0.75 
 
 1.5 
 
 7 
 
 0.4 
 
 0.8 
 
 0.18 
 
 1.2 
 
 1.8 
 
 Eosinophilic mye- ) 
 locytes j 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 0.4 
 
 0.36 
 
 0.8 
 
 0.2 
 
 Vesicatory cells 
 
 0.4 
 
 2.0 
 
 1.0 
 
 2.8 
 
 
 
 
 
 1.5 3.5 
 
 
 
 1.6 
 
 
 
 0.76 1.2 
 
 1.7 
 
 0.4 
 
 I. Pulmonary tuberculosis at the third stage. 
 
 II. Pulmonary tuberculosis at the third stage. 
 
 III. Pulmonary tuberculosis at the third stage. 
 
 IV. Pulmonary tuberculosis at the second stage. Infiltration of 
 the entire left lung. 
 
 V. Pulmonary tuberculosis in the second stage. Generalized 
 bronchitis. 
 
 VI. Pulmonary tuberculosis in the second stage. 
 
 VII. Pulmonary tuberculosis in the second stage. Generalized 
 bronchitis. 
 
 VIII. Pulmonary tuberculosis in the third stage. Intense fever. 
 
 IX. Pulmonary tuberculosis in the third stage. Hemoptys - 
 Fever. Erysipelas cured since twenty-six days. (Notice the small 
 number of neutrophilic polynuclears and the large percentage of the 
 mononuclears) . 
 
 X. Tubercular pulmonary congestion. 
 
622 IXFECTIO US DISEASES. 
 
 XI. Pulmonary tuberculosis with fibrinous evolution. Tubercular 
 peritonitis. 
 
 XII. Slight pulmonary tuberculosis. Dulness in the front and 
 right side of the chest and the left side of the back ; harsh respiration : 
 a few dry rales and frictions. Apyrexia. 
 
 XIII. Acute. serofibrinous pleurisy. 
 
 XIV. Acute serofibrinous pleurisy in a very vigorous man. 
 
 XV. Acute serofibrinous pleurisy on the way to recovery. Intense 
 gastrointestinal disturbances and hypothermia since the previous 
 day. 
 
 In erysipelas the eosinophils, which are absent when the disease 
 is at the stationary period, reappear at the moment of recovery. 
 These elements, however, are few in number during the days imme- 
 diately following the morbid termination. The organic reactions 
 which are profoundly modified by the infectious attack, remain 
 disturbed for a long time. At the same time that the percentage 
 of the eosinophils increases, that of the neutrophilic polynuclears 
 diminishes at the end of the disease. The mononuclears are also 
 far more numerous than at the stationary period. 
 
 We have employed the vesicatory test in two cases of mumps and 
 one of acute angina. All these observations concur in demonstrat- 
 ing that the histological examination of the vesicatory fluid reveals 
 the mode of reaction of the hematopoietic organs in a given case. 
 In fact, we see that the same toxic cause, the application of canthar- 
 ides, determines the presence of different cells in the vesicatory fluid 
 according to the degree of intensity of the infectious impregnation, 
 according as the organism resists with more or less success, and 
 according to the phases of the struggle. This method is extremely 
 sensitive. A superadded or even slight infection suffices to com- 
 pletely modify the results. It must, however be remembered that 
 the vesicatory test indicates only the degree of intensity of infectious 
 impregnation. An intense infection may be benign, for example, 
 an acute angina. A slight infection may be more serious, even if 
 the organism resists, for example, a local tuberculosis. The vesic- 
 atory test furnishes data concerning not the absolute prognosis of 
 the infection, but the degree of impregnation of the organism. 
 From a purely theoretical standpoint it is interesting to remark 
 how an infection, though benign and well localized, modifies all the 
 organic reactions. A catarrhal angina is sufficient to disturb the 
 leucocytic equilibrium of the economy. Under these conditions the 
 
DIAGNOSIS AND PROGNOSIS OF INFECTIOUS DISE I E 623 
 
 same irritating cause produces other effect* than in s normal indi- 
 vidual. Our investigations thu explain why econdary Infection/ 
 so often differ in their mode of evolution from primary infection . 
 
 Diagnosis According to Chemical Modifications in Fluids. An 
 infection produces no1 only histological bul also chemical modifica- 
 tions in the blood and fluids, It causes notably the appearance in 
 the serum and certain exudates of substances which -•■••in to be 
 intended to combal infection. Among these the mosl interesting 
 from a diagnostic standpoinl is thai which causes agglutination of 
 the microbes. Everyone is well acquainted with the practical 
 application which Dr. Widal has made of this in the diagnosis of 
 typhoid fever. The procedure is quite simple. A few drops of fin- 
 blood of the patienl are taken, and then the serum, diluted in a 
 certain proportion, is mixed with a fresh culture of Eberth's typhoid 
 bacillus. If the case is one of typhoid fever, the scattered elements 
 unite in small masses. This method, designated as the "method of 
 serum-diagnosis," is currently employed in the diagnosis of typhoid 
 lover. According to the researches of Dr. Arloing and his disciples, 
 this method is applicable also to tuberculosis. Other Bubstances 
 which arc produced in the blood of infected subjects may Likewise 
 serve in diagnosis. 
 
 Among the secretions only one is commonly studied clinically, 
 namely, the urine. Its examination in the course of infectious dis- 
 eases is of great importance, but it is more interesting for progno>b 
 than diagnosis. The modifications in quantity and color, the varia- 
 tions in the amount of cells and nitrogenous substances, the appear- 
 ance of abnormal substances, such as albumin, peptones, and glue* ise, 
 enable us to appreciate the changes occurring in the organs and in 
 general nutrition, but do not help us to determine the nature of 
 the disease. Likewise, the detection of biliary pigments — urobilin— 
 is interesting only as regard's prognosis. The only reaction which 
 sometimes may serve for diagnostic purposes is Ehrlich's diazo 
 reaction. Although it is not absolutely a specific, this reaction is 
 an important sign in the diagnosis of typhoid fever. It is sometime s 
 manifest as early as the third or fourth day. but may be delayed 
 until the beginning of the second week. It also enables us to fore- 
 tell certain complications. If it suddenly ceases unattended by 
 concomitant amelioration, some secondary infection or a renal lesion 
 must be suspected. If it increases in intensity it means an aggrava- 
 tion of the disease. Its reappearance during convalescence indicates 
 
(324 IXFECTIO US DISEASES. 
 
 a relapse. The diazo reaction is likewise observed in typhus fever, 
 in acute tuberculosis, pyemia, septicemia, measles, scarlatina, and 
 at times in pneumonia. 
 
 Diagnosis by Therapeutics. We must now say a word regarding 
 the influence of certain substances capable of modifying the evolution 
 of affections and thus elucidating their character. Such are specific 
 medicines, which serve to determine, as the case may be, the malarial 
 or syphilitic nature of an infection. The action of quinine upon 
 malaria is too well known to need more than an allusion. Syphilis 
 has two specifics: salts of mercury and iodide of potassium. The 
 test treatment is constantly employed in the diagnosis of difficult 
 cases. It should be remembered, however, that the action of the 
 iodides is exercised in the same manner in another infection, namely, 
 actinomycosis. The specific character and diagnostic value of the 
 iodides thus lose much of their importance. It is even likely that 
 many cases of actinomycosis have been mistaken for instances of 
 tertiary syphilis. 
 
 Diagnosis by Microbic Toxins. While the number of specifics 
 drawn from the inorganic world are so small in number, it is hoped 
 that microbic cultures will furnish some such specifics. This hope 
 is founded upon the investigations of Koch. In studying the effects 
 of tuberculin, this author showed that the reactions differ markedly 
 according as this extract of cultures of tubercle bacilli is injected 
 into a healthy or a tubercular individual. At the end of four to 
 five hours after the injection a chill occurs, and the temperature 
 rises as high as 102.2°, 104° F. and even higher, 105.8° F. (39°, 40° C. 
 and even 41° C). The patient feels tired. He is tortured by con- 
 stant coughing, has at times nausea and vomiting. He experiences 
 very intense pain in the epigastrium, extremities, and articulations. 
 These symptoms last from twelve to fifteen hours ; but may be pro- 
 longed for two or three days, or be followed by a secondary fever 
 after the cessation of the reaction, depending upon infect on by other 
 microbes (pneumococci, staphylococci), the development of which is 
 favored by the so-called "lymph." Coincidently with these general 
 disturbances local phenomena in the tubercular lesions are produced, 
 which may readily be appreciated by observing what occurs in the 
 case of lupus. The diseased parts swell and become red. Here and 
 there they become brown and necrosed. Two or three days later 
 the redness diminishes and the lesion is covered with yellowish crusts 
 formed by the air-dried serum. Two or three weeks later the crusts 
 
DIAGNOSIS AND PROGNOSIS OF INFECTIOUS DISEASES, 026 
 
 become detached, and in favorable ca es leave •■• cicatrix of good 
 appearance. Several injections are generally required to obtain this 
 result. In tuberculosis of the lymphatic glands, as well a ino 
 and articular tuberculosis, the reactions are less intense, bul they 
 
 live, always percept ible. 
 
 It, was, therefore, hoped thai the so-called "lymph" would i 
 to diagnose tuberculosis, and thu e tablish the nature of at uspicioui 
 lesion and also to decide whether an old focue was really cured. 
 The specific value of tuberculin is notably diminished by the fad 
 that it produces intense reactions in non-tubercular cases, for 
 instance, in cases of cancel-, sypli' lides, scarlal in;i, gonorrheal cystitis, 
 leprosy, and actinomycosis. Several authors, and particularly Maydl, 
 have observed a typical reaction in healjbhy individuals who had 
 received only one or I wo milligrams of the ' ' lymph. " On the other 
 hand, the injection does nol always produce reactions in tuberculous 
 subjects. Sometimes the general phenomena, and sometimes the 
 local manifestations, are lacking. Furthermore, various substances, 
 microbic or otherwise, may produce in tuberculous individuals dis- 
 turbances similar to those caused by tuberculin. Injections of 
 artificial serum are often followed by marked reactions, and, 
 shown by Hutinel, these may be utilized for diagnosis. We may. 
 therefore, conclude that Koch's "lymph" is not absolutely specific. 
 Other substances behave in the same manner, and it does not act 
 exclusively upon tubercular lesions. Nevertheless, some authors 
 think that it may still be profitably employed at least in animals. 
 German veterinarians who have studied its action upon tubercular 
 cows have obtained reactions with doses of 3 to 10 centigrams, which 
 produce no disturbance whatever in healthy cows. 
 
 Mallein. The discovery of tuberculin by Koch led bacteriologists 
 to search for analogous substances in other cultures. Thus Helman 
 and Kalning prepared a substance designated mallein. winch has 
 been the subject of numerous investigations, especially by Preuss 
 Pearson, Foth, Babes, Nocard, and Bonome. 
 
 Inoculation of mallein into animals suffering from glanders pro- 
 duces at the injected point a hot, painful tumefaction which incr< s - 
 for twenty-four or thirty-six hours, and disappears in eight or ten 
 days. Synchronously the general state is modified. There is pros- 
 tration; the animal looks depressed, anxious: its breathing is ac- 
 celerated, and it may have chills and convulsions. A febrile move- 
 ment finally sets in which reaches its maximum after ten or twelve 
 
 40 
 
626 INFECTIOUS DISEASES. 
 
 hours, seldom later. The rise in temperature amounts to 2.7° to 
 4.5° F. (1.5° to 2.5° C). It is to be noted that the mallein test is 
 conclusive only in those cases in which the inoculation is made upon 
 animals having previously been at rest for forty-eight hours and 
 protected, after inoculation, against atmospheric variations. 
 
 If reaction is clear — i. e., if the thermal elevation is regularly 
 produced and reaches 2.7° F. (1.5° C), the existence of glanders 
 may be affirmed with a fair degree of assurance. If the temperature 
 is raised 3.6° F. (2° C), diagnosis is positive, and the animal is killed. 
 When reaction is incomplete or irregular the animal is left at rest 
 for four to six weeks, and then the experiment is resumed with 
 little larger doses. 
 
 The employment of mallein has rendered immense service. By 
 revealing with a fair degree of certainty the existence of glanders 
 and treat it from the very beginning, mallein will certainly serve 
 to decrease and finally extinguish this disease. The mallein test 
 may also be applied to man, provided small doses are employed. 
 It has thus been injected with success by Bonome and by Buscke. 
 
 Recapitulation. The foregoing various scientific procedures of 
 diagnosis, which are mostly drawn from recent bacteriological dis- 
 coveries, may render immense service to the nosologist by enabling 
 him to give a solid basis to clinical observations; but they are of 
 less importance in practice. In spite of their apparent simplicity, 
 they require a vast amount of technical experience, and the positive 
 character of laboratory researches renders possible quite harmful 
 errors. It should not, therefore, be imagined, as is too often done, 
 that bacteriology will furnish the physician with simple and certain 
 procedures. The difficulties, although of a different character, exist 
 none the less. Even supposing that the practitioner has acquired 
 sufficient skill to utilize the modern methods of investigation, it 
 must be remembered that bacteriology is incapable of solving all 
 the problems which confront the physician in connection with each 
 particular case observed. When he recognizes that the disturbances 
 are due to a definite microbe he will not have finished his task. A 
 complete diagnosis must answer many other questions. For ex- 
 ample, a patient whose expectorations contain the pneumococcus, 
 and whose respiratory apparatus is the seat of a lesion dependent 
 upon this microbe, may have a bronchitis, or a capillary bronchitis, 
 or a bronchopneumonia, or a fibrinous pneumonia. The same 
 microbe is concerned in all four instances; but the affection pro- 
 
DIAGNOSIS AND PROGNOSIS OF INFECTIOUS DISEASES. 627 
 
 duced is quite different from the quadruple Btandpoinl of anatomico- 
 pathological localization, evolution, prognosi . and treatment. I' 
 may be answered bhal the nature of the morbid reaction i no1 of 
 prime importance, and thai the point to be decided i- the nature 
 of the pathogenic agent. As soon ac this is done the specific treat- 
 ment can be applied and the evolution of the disease arrested. For 
 the present, however, this is a dangerous Utopia. Even in thi 
 of diphtheria, the only infection for which we pot i iecific, the 
 
 physician will be bitterly disappointed if he fancies thai i1 suffices 
 to inject antitoxin as soon ;is the bacillus is discovered. On the 
 contrary, lie must establish a complete diagnosis, determine the 
 state and extent of the lesions, and learn under what conditions 
 these develop and in what kind of soil they evolve. 
 
 Rules of Clinical Diagnosis. It is evident that the questions 
 which must be solved in the presence of a patient apparently suffer- 
 ing from an infection vary from one case to another. They may, 
 nevertheless, be grouped in the following manner: 
 
 1. What are the present disturbances? The sensations felt by 
 the patient, the objective phenomena which he presents enable the 
 physician to answer this first question. He may thus lay down 
 the symptoms which he observes. 
 
 2. What is the immediate cause of these disturbances, namely, 
 with what organs or systems are they to be associated? This second 
 question is more difficult. In fact, symptoms are divided into two 
 groups. Some of them express the suffering of an organ and imme- 
 diately draw the attention of the physician to this organ. Cough 
 or dyspnea leads him to auscultate the lungs. Palpitation of the 
 heart leads him to examine the heart, and impotence of the lower 
 extremities leads him to study the nervous system. If. however, 
 he weighs the close synergies connecting the various parts of the 
 organism he will remember that the disorders of these organs may 
 depend upon some other organ. Thus we arrive at the third question. 
 
 3. Are the suffering parts primarily or secondarily affected'? Are 
 their disorders or lesions independent or due to the same cause? 
 Among the organs affected, in which one did the disorders upon 
 which the other symptoms depend first become manifest'? 
 
 All these questions may be solved only in one way. The physician 
 must examine systematically the various parts of the organism, 
 those which seem to be diseased as well as those which appear 
 healthy. 
 
628 INFECTIOUS DISEASES. 
 
 4. The succession of the present symptoms having been estab- 
 lished, the physician must solve the question whether the present 
 affection is the result of a previous disease or whether it is a primary 
 malady. 
 
 5. In the latter instance he must investigate the nature of this 
 disease and its place in nosology. It is here, and here only, that 
 modern procedures intervene, and bacteriology, at least in certain 
 cases, may profitably be resorted to. However, even when a search 
 for the microbe enables the physician to assign to the disease its 
 true place in nosology, his task is not yet completed. He has a last 
 and, perhaps, the most important question to solve, for the diagnosis 
 and part of the treatment depend upon it, namely: 
 
 6. In what soil is the disease evolving? What clinical form does 
 it assume? What organs are secondarily involved? Having made 
 a complete examination of the patient, the physician, in most cases, 
 finds sufficient data to answer the questions connected with the 
 diagnosis. Although he cannot always reach definite conclusions, 
 he can at least make a more or less close approach to accuracy. 
 At the beginning of the disease he may remain in doubt, but he 
 hesitates only between two or three hypotheses, and, in general, 
 after a daj^ or two the evolution of the disease, by modifying the 
 clinical aspect, leads him to an exact and definitive conception of 
 the events. Thus, for example, he is called to decide the case of 
 a child or a young man suddenly attacked by angina. He finds 
 fever, a rapid pulse, a coated tongue, and a red throat with some 
 yellowish exudate upon the tonsils. The diagnosis of acute angina 
 is evident, but what is the nature of this angina? This is more 
 difficult to determine, and yet the question is of prime importance 
 from a prognostic and therapeutic standpoint. The sudden onset, 
 the pultaceous aspect of the tonsillar deposit, and the frankly 
 inflammatory reaction lead the physician to eliminate diphtheria. 
 But is the case one of simple angina or of a scarlatinal angina? 
 The age of the subject, intensity of the fever, the intense redness 
 of the throat, the rapidity of the pulse, and at times the existence 
 of a concomitant epidemic, cause the physician to incline to a 
 diagnosis of scarlatina. A final decision is impossible, however. 
 He must wait for the appearance of the eruption, that is, until the 
 third day of the disease, in order to definitely decide the question. 
 In this instance, a symptomatic manifestation of prime importance 
 in diagnosis is lacking. 
 
DIAGNOSIS AND PROGNOSIS OF INFECTIOUS DISEASES. 629 
 
 Id other cases an exaci diagnosis, which 3eero to be justified l>y 
 no symptom, may be laid down from the very beginning. Thus ;i 
 child eight or ten years of age is suddenly taken by intei 
 It suffers from dyspnea and a very irritating dry cough. The face 
 is congested, the cheeks red, and the temperature a1 lor I K) I 
 Although auscultation gives negative results, the physician diagi 
 pneumonia, and, in reality, after twenty-four hours, sometimes after 
 two or three rhiys, the characteristic bronchial murmur i- heard. 
 Owing to a little practice the diagnosis was made a1 the outsel i/i 
 spite of the absence of stethoscopic signs and in spite of the presence, 
 in certain instances, of nervous phenomena and even convulsions, 
 which might first lead to a diagnosis of meningitis. 
 
 It would be easy to multiply illustrations. These few suffice to 
 establish that, in most infections, diagnosis may be made if the 
 whole organism is systematically and minutely examined. 
 
 When the physician has recognized the nature of the disease he 
 has not yet completed his task. Let us suppose the case of a man 
 who has been suddenly taken by a chill, followed by pain in the side. 
 an irritating cough, brick-dust expectoration, and intense fever. 
 On auscultation we find in one of the lungs a focus of crepitant 
 rales or tubal murmur. The state of the lung explains all the dis- 
 orders, and the evolution of the disease enables us to state that we 
 are dealing with an infection — i. e., pneumonia. We have thus 
 answered all the questions which we had to solve, except the last 
 one. It was easy to make the diagnosis of pneumonia in this 
 instance. 
 
 It is more difficult to determine in what soil the infection evolves. 
 In this connection it is important carefully to interrogate the patient 
 as regards his hereditary as well as personal morbid antecedents. 
 In this connection, also, all the viscera must be carefully examined. 
 The physician does well to auscultate the lungs in order to recognize 
 the disease; but he must never be contented with so summary a 
 diagnosis. The prognosis and the treatment are to be based upon 
 the knowledge he acquires of the previous condition of the subject 
 and the present state of the various organs. Then, and then only. 
 will he reach a complete diagnosis and be able to foretell the evolution 
 of the disease. If pneumonia develops in a young and vigorous 
 individual, recovery is the rule. If it occurs in an aged person, 
 the termination is in most cases fatal. In both of these instances 
 pathology seems to furnish sufficient information. Let us now 
 
630 INFECTIO US DISEASES. 
 
 consider an apparently vigorous patient attacked by pneumonia. 
 One might believe that he will recover without much hinderance. ( )n 
 making a systematic examination of his organs and an analysis of 
 the urine a lesion until then latent is discovered, a cardiac affection, 
 a sclerosis, or else albuminuria, or glycosuria, or, lastly, there are 
 found secondary localizations in other organs, endocarditis or myo- 
 carditis. The evolution will then be different. An exact conception 
 of the disease is obtained by careful examination of the entire 
 organism. 
 
 The example which we have chosen was a simple one. At any 
 rate, it may be said that it is relatively easy to diagnose an infectious 
 disease. The physician has to deal with a recent acute evolution, 
 all the phases of w T hich are observable, since he is examining the case 
 at a stage quite near the beginning of the evolution. In most cases, 
 in order to arrive at a diagnosis, it suffices to have studied pathology 
 well. The only important point is to make a complete diagnosis, 
 for, as we have often repeated, the manifestations are far more 
 diffuse than is at first believed. The microbic toxins affect the 
 whole economy, and the duty of the clinician is to learn what parts 
 are affected and in what degree they are involved. To find the 
 designation under which the infection is to be classed is a relatively 
 easy task: but diagnosis, however exact it may appear to be, is 
 incomplete and insufficient, and answers only the first, the easiest 
 and the least important part of the problem. 
 
 In order to facilitate the task of the physician, nosologists have 
 admitted a certain number of clinical forms in infectious diseases. 
 Taking typhoid fever and pneumonia as examples, we have shown 
 how it is possible, by considering either the state of the subject or 
 the general disturbances or the localizations, to classify the various 
 types and furnish precise indications for the guidance of the physician. 
 These forms, however numerous they may be, do not, of course, 
 respond to all the clinical varieties and their innumerable variations ; 
 but they may supply valuable data, and must, therefore, be most 
 carefully studied. In certain instances the complexity of the 
 clinical form is due to the coexistence of various manifestations or 
 multiple localizations. It is, therefore, very difficult at times to 
 connect them with each other. Thus, we may have to deal with a 
 case of erysipelas in which, at a given moment, a pulmonary murmur 
 is detected. Is the process a streptococcic infection — i. e., a visceral 
 localization dependent upon the agent which has caused the first 
 
DIAGNOSIS AND PROGNOSIS OF INFECTIOUS DISEASES. <;;',] 
 
 disease? or is it an infection due to a superadded microbe, the 
 
 I >i kmi 1 1 k >f< if-ci is ? lioi.li varieties of pneumonia have been ob ei 
 in erysipelas, and, withoul bacteriological examination of the sputa, 
 it is generally impossible to make the diagno i 
 
 The difficulty is still greater when the pathogenic agenti are 
 unknown. In an individual presenting a scarlatiniform eruption 
 coincident with other infectious manifestations, how can we affirm 
 whether the case is one of erythema or a true scarlatina? It would 
 be equally right to hesitate in certain cases in which multiple artic- 
 ular symptoms occur in scarlatinal patients a1 the period of con- 
 valescence. Do they depend upon scarlatina or a concomitanl 
 acute articular rheumatism? Nol infrequently the physician re- 
 mains in doubt with regard to all these questions. In order to 
 classify and interpret the disturbances, the physician does not need, 
 as is often stated, a particular talent, a sort of divining gift. The 
 skill of making a diagnosis is not inborn. On the contrary, it is 
 acquired by theoretical and pr.-iclical study of pathology and by 
 repeated examination of patients. As a matter of fact, we see in 
 clinics cases far more complex than the study of pathology makes 
 us believe. Didactic studies give only schematic descriptions. 
 They consider diseases in their fundamental and constant characters, 
 regardless of the soil in which they run their course. It is precisely 
 because this soil is so eminently variable that clinical types are so 
 numerous and varied. The duty of the physician is, therefore, to 
 determine the soil in which the disease evolves, and from this deter- 
 mination he must draw the greater part of his knowledge of its 
 ulterior evolution. 
 
 After the physician has succeeded in discovering the present state 
 of the patient, his resistance, his reactionary aptitudes, the functional 
 activity and alterations of his organs, he will be in a position to 
 predict the evolution of the process he observes. To answer this 
 last question is to establish a prognosis, that is, to solve the most 
 difficult and important problem in medical art. 
 
 Prognosis. 
 
 It is evident that, in the matter of prognosis, the nature of the 
 disease is first to be considered. Certain infections almost always 
 terminate fatally, and others end in recovery. In such cases prog- 
 nosis is drawn simply from diagnosis. Tubercular meningitis, acute 
 
632 ISFECTIOUS DISEASES. 
 
 mania, and hydrophobia are always or nearly always fatal. On the 
 other hand, varicella, mumps, herpetic anginas, and simple pneumonia 
 in children always or nearly always end in recovery. Nothing seems 
 to be simpler. Even in these cases, however, there are exceptions. 
 Varicella at times proves fatal, and a good number of distinguished 
 physicians assort that tubercular meningitis is curable. These ex- 
 ceptions, one may say, should not be taken into account. Let us, 
 therefore, set aside these facts and consider the most frequent cases. 
 When we have to deal with an infection with variable prognosis, 
 whence shall we draw our data of appreciation? We may first 
 resort to statistics. From this point of view I have looked up the 
 observations in our wards during the last five years. These obser- 
 vations are 8832 in number, comprising 602 fatal cases, that is, a 
 proportion of 6.8 per cent. From tabulation of these figures v?e 
 may draw certain important conclusions with reference to prog- 
 nosis. In fact, it will not suffice to consider the results in a general 
 way. Although it is interesting to know what the general mor- 
 tality is in each disease, it is indispensable to push analysis a little 
 further. Here are some conclusions regarding the influence of age 
 and sex upon prognosis : 
 
 Influence of Age. It may broadly be stated that mortality is 
 very high during infancy and is considerably reduced after two 
 years of age. In the adult, according to the disease under considera- 
 tion, mortality may be greater or less than that in second childhood. 
 Thus, in measles, scarlatina, varicella, diphtheria, and anginas the 
 mortality in adults is far below r that in children. Such is not the 
 case with erysipelas. The mortality, which is 45 per cent, before 
 two j^ears, falls to between tw r o and fourteen years of age. Between 
 fifteen and thirty years it hardly exceeds 1 per cent.; then it rises 
 with age. It oscillates around 4 or 5 per cent, from thirty-one to 
 fifty years of age. It may be remarked that, during infancy, ery- 
 sipelas kills of itself by streptococcic generalization. In the adult, 
 on the contrary, death commonly results from a complication or a 
 previous organic lesion which has weakened the resistance. The 
 influence of age is no less important in other diseases, especially in 
 measles. During infancy the mortality reaches 27.7 per cent It 
 falls to 6.6 per cent, in childhood, and to 0.8 per cent, in adults. 
 Three principal factors explain the higher percentage in young 
 children, namely, bronchopneumonia, tuberculosis, and suppura- 
 tions and gangrenes. The influence of measles upon the course of 
 
DIAGNOSIS AND PROGNOSIS OF INFECTIOUS DISE ISEl 
 
 tuberculosis has long been noted. The younger the ubjed the 
 more marked is the action of this eruptive fever upon the evolution 
 of tuberculosis. Bronchopneumonia, suppurations, and gang] 
 (Icpciid upon common germs, which are closely allied to each other, 
 and upon pus-cocci. Young children are particularly predisp 
 to the action of these bacteria, but they run the risk of infection 
 especially when they are placed under bad hygienic conditions. 
 The frequency and gravity of superadded pyogenic Infections in 
 young children are likewise proved by the study of other disc 
 Scarlatina, which has little tendency to afifecl the respiratory <<<■_ 
 may kill al this age by bronchopneumonia. Finally, varicella, 
 which is too often considered as a mild disease, gives a mortality 
 of more than 7 per cenl . 
 
 Influence of Sex. The influence of sex, which is nil during child- 
 hood, varies in adult age according to the disease under considera- 
 tion. According to our statistics, mortality is the same in hoth 
 sexes for scarlatina, somewhat higher in men in measles and especi- 
 ally in variola. For the latter infection, the mortality is 26.2 per 
 cent, in men, and 22.1 per cent in women. The differences are 
 analogous in erysipelas. In this affect ion the mortality is 5.99 per 
 cent, in men, and 3.67 per cent, in women. I believe that the 
 higher percentage of mortality in males is due to the influence of 
 alcohol. Chronic intoxication by alcohol causes nutritional disturb- 
 ances and visceral lesions which lend a particularly serious character 
 to infections. In measles and scarlatina mortality is nearly the 
 same in both sexes, because the individuals attacked are still very 
 young and are not yet sufficiently impregnated with alcohol. Variola 
 and erysipelas are often observed in individuals more advanced in 
 age, and, therefore, the mortality in men is higher than in women. 
 
 This is the information that may be drawn from the statistics. 
 In spite of their interest they are insufficient to assist materially 
 in diagnosis. Therefore, in order to foretell the probable evolution 
 of a disease it is necessary to consider the data of another order. 
 
 Influence of Epidemics. The elements which serve as a basis 
 for prognosis may be divided into two groups. On the one hand, 
 the characters of the disease must be considered, viz.. the condition? 
 under which it is developed, the symptoms it presents, and the course 
 it follows. Next, the soil in which the disease evolves is to be 
 studied. The first information is furnished by epidemiology. It is 
 known that at certain moments diseases become aggravated or 
 
034 INFECTIOUS DISEASES. 
 
 attenuated. We often notice changes in the evolution of influenza, 
 pneumonia, and typhoid fever. For a few years past diphtheria 
 was very benign. At present it seems to assume a more serious 
 character. The same remark may be made with regard to scar- 
 latina. Moreover, it is known that in the course of the same epi- 
 demic the gravity follows a course nearly parallel to that of mor- 
 bidity. Benign cases are frequent at the end of the epidemic. 
 The hygienic conditions under which a patient is placed should also 
 be taken into consideration, whether he is being treated in a hospital 
 or at home. These are evident truths upon which it is useless to 
 dwell. 
 
 Importance of Etiological Conditions. Certain importance is 
 often attached to the knowledge of the etiological conditions. It 
 has been demonstrated, however, by a great many examples that a 
 disease contracted from a profoundly infected individual may prove 
 to be benign, and vice verm. In this connection, nothing is more 
 instructive than the study of venereal infections. In many cases 
 in which these affections have been transmitted to several individuals 
 under etiological conditions as similar as possible, the evolution in 
 the various subjects has been quite different. In certain cases, 
 however, an exalted virus produces, by contagion, grave diseases. 
 To be convinced of this, it will suffice to state what occurs with 
 regard to pneumonia in certain family epidemics. By thus follow- 
 ing the course of these infections successively contracted we may 
 often see the process become more and more serious as it spreads. 
 The person first attacked has a benign infection, which assumes a 
 progressively graver character as it is transmitted to persons about 
 him. Analogous observations have been made by Dr. Quelme with 
 regard to dysentery in Bretagne. 
 
 In the case of an inoculated infection prognosis depends partly 
 upon the mode of entrance of the virus. The gravity of extragenital 
 syphilis has long been known. A better example is furnished by 
 hydrophobia. Not to speak of cases in which bites inflicted upon 
 parts protected by clothing produce no symptoms, statistics show 
 that wounds of the fingers and face are particularly serious, because 
 these regions are rich in nervous terminations. The mortality is 
 about 87 per cent, for bites of the face, 66 per cent, for those of the 
 hands, 29 per cent, for those of the upper extremities, and 19 per 
 cent, only for those of the lower. Finally, it may be stated that 
 in the case of infections which may be transmitted by several pro- 
 
DIAGNOSIS and PROGNOSIS OF INFECTIOUS DISEASES. 636 
 
 cedures prognosis is least serious in accidental inoculation. Glanders 
 produced by subcutaneous inoculation is quite often cured. I' if 
 likewise known that the prognosis of anatomical tubercle i.e., con- 
 tracted at necropsy is generally favorable. 
 
 Importance of the Duration of Incubation and of the Mode of 
 Invasion. When the momenl in which the infection has occurred 
 can be determined, it is possible lo <lr;i,w some information from the 
 length of incubation. We have already Qoticed thai the period of 
 incubation is abridged under two quite dif'ferenl circums1;inccs, 
 namely, when the virus is very active and, consequently, the prog- 
 nosis is evidently grave, or when the organism is capable of very 
 energetic reaction and the incubation is short and of f;ivor;ible signifi- 
 cance. The difference will be appreciated in view of the concomitanl 
 circumstances. 
 
 The same remarks are applicable to the mode of invasion. With 
 a very sudden and tumultuous onset, an infection may be very 
 benign and even very short. Therefore, to exactly appreciate the 
 importance of the mode of onset, we must consider the accompanying 
 phenomena. If these are not very intense this suddenness of the 
 initial manifestations indicates a favorable evolution. If they are 
 intense, a grave, or at least a serious, form may be predicted. In 
 certain instances the knowledge of the initial manifestations may 
 serve in diagnosis. Thus, surgeons have established an important 
 difference between phlegmons which begin with local phenomena and 
 those attended from the first by general reactions. In the latter 
 instance the profounder impregnation of the organism is connected 
 with a greater gravity of the process. 
 
 A relationship is generally believed to exist between the duration 
 of invasion and the gravity of a disease. This the author does not 
 believe to be true except with respect to variola. In this infection 
 a short invasion, not exceeding two days or two and a half days, is 
 a sign of confluent variola. An invasion lasting three or four days 
 indicates a discrete variola. It is true that an eruption beginning 
 after four full days is seldom confluent. This, however, is acceptable 
 with some reservation. 
 
 Bases of Prognosis at the Stationary Period. As a rule, when a 
 disease has reached the stationary period the physician possesses all 
 the necessary elements for prognosis. These elements are four in 
 number: First, the local lesion or the principal expression of the 
 infection — the eruption in cases of eruptive fevers. Second, the 
 
636 INFECTIOUS DISEASES. 
 
 state of the parts surrounding the local lesion. Third, the general 
 phenomena. Fourth, the condition of the principal organs. 
 
 Let us immediately remark that if an analytical examination is 
 necessary, the prognosis must be established in view of the ensemble 
 of the researches above indicated. To determine the extent of the 
 local lesion or the intensity of the general phenomena does not suffice- 
 These two orders of manifestations must be compared in order to 
 draw a conclusion It may broadly be stated that prognosis is grave 
 in proportion as the local lesion is intense and especially extensive. 
 This is true as regards pneumonia as well as eiysipelas and the erup- 
 tive fevers, and particularly so with respect to variola. The prog- 
 nosis of the latter disease depends entirely upon the character of the 
 eruption. Of course, the study of the general phenomena is impor- 
 tant, but that of the cutaneous manifestations is still more important. 
 The condition of the parts surrounding the local lesion must, as a 
 rule, be taken into consideration. In the case of pneumonia and 
 tuberculosis the information furnished by the examination of the 
 portions of parenchyma spared by the principal process is of consid- 
 erable importance. The phenomena of congestion or edema which 
 may take place therein greatly affect the prognosis. 
 
 As already stated the conditions of the local lesion and of the 
 general state must be compared. Violent general reactions are much 
 less grave than adynamic manifestations. 
 
 Finally, the examination must be completed by determining the 
 condition of the organs, heart, lungs, and liver, and by analyzing the 
 urine. Thus information is obtained concerning the function of and 
 the possible complications occurring in the viscera. This comple- 
 mentary examination shows the influence of the present infection 
 upon the principal organs, and thus enables us to form an idea of the 
 previous condition and pre-existing lesions of the organs. In this 
 manner we obtain valuable indications for prognosis, for it is not 
 sufficient to determine the characters of the present disease, its 
 intensity, and the lesions which it produces or complications to which 
 it gives rise. We must know the soil in which the disease evolves 
 in order to establish the prognosis. 
 
 We hardly need dwell upon the importance of the general state of 
 the individual at the time when he is attacked by an intercurrent 
 disease. We know the gravity of an infection attacking a cachectic, 
 emaciated individual having suffered privations, exposure, overwork, 
 and excessive fatigue. In all debilitated individuals evolution is 
 
DIAGNOSIS AND PROGNOSIS OF INFECTIOUS DISEASES. 637 
 
 grave, and, the defensive reactions being often nearly impossible, •'' 
 fatal termination soon takes place. Fatigue and overwork not only 
 render prognosis unfavorable by aggravating the cour e of the dis- 
 ease, but also by favoring certain morbid localization . We 
 already referred to the frequency of myocarditii in overworked indi- 
 viduals. In certain cases the cardiac infection ends in the formation 
 of an abscess. In other instances overexertion gives rise to cerebral 
 localizations. It will suffice to recall the frequency of delirium under 
 these conditions. We have a more palpable illustration in cerebral 
 rheumatism, a grave manifestation which is observed only among a 
 certain class of individuals. 
 
 Nutritional disturbances dependent upon a diathetic state like 
 exercise an unfavorable influence upon the course of infections. The 
 gravity of infections in the obese may be cited as an example of this. 
 The very thick adipose tissue seems to prevent the dissipation of heat 
 in fever. On the other hand, the disorders of nutrition engendered 
 by obesity render the reactions sluggish and less energetic. Hence. 
 after the termination of the disease its effects are prolonged beyond 
 the usual limits. The ill-nourished skin is easily invaded by external 
 germs. Not infrequently furuncles, anthrax, and especially sloughs 
 occur, particularly in the sacral region. 
 
 Among the diseases connected with disturbances of nutrition we 
 may cite gout and diabetes. In this connection gout is of little 
 importance. We have observed several cases of erysipelas in gouty 
 individuals in whom the evolution terminated in a favorable manner. 
 The role of diabetes is more important. It is known that this di- 
 predisposes to cutaneous infections, pulmonary inflammations and 
 tuberculosis. It imparts to these processes a particularly rapid and 
 grave evolution. Infections of the skin and lungs are easily compli- 
 cated with gangrene. In other cases pneumonia assumes a galloping 
 course. The gravity of infections should not, however, be exagger- 
 ated as regards diabetic patients. We have seen several such patients 
 attacked by erysipelas, and all recovered. It is true that the infec- 
 tion was particularly intense, attended by delirium, and prolonged 
 beyond the average duration. 
 
 Another element of prognosis is drawn from the knowledge of pre- 
 vious infections and especially intoxications of the individual. With 
 reference to relapsing infections it has been asserted that successive 
 attacks gradually lose their intensity. This law does not seem to 
 the author quite true. It is not true with regard to erysipelas, and 
 
638 IXFECTIO US DISEASES. 
 
 many case? are on record in which individuals have succumbed to a 
 second or third attack of variola. 
 
 In treating of microbic associations we have shown the role of 
 previous or concomitant infections and emphasized the fact that 
 results varied according to the case under observation. It may be 
 recalled that erysipelas occurring during convalescence from scarla- 
 tina is very benign, while pneumonia supervening in the course of 
 erysipelas is always highly dangerous. It is evident that a pre- 
 existing chronic infection aggravates the prognosis of an intercurrent 
 infection. This is true as regards syphilis, malaria, and especially 
 tuberculosis. Furthermore, intercurrent disease may awaken a pre- 
 vious infection, bring about a recurrence of malarial paroxysms, and 
 impart to a chronic tuberculosis an acute course. 
 
 Previous intoxications likewise modify prognosis. Owing to dis- 
 turbances of nutrition and the organic lesions to which they give 
 rise, they aggravate infections. Alcoholism is to be considered in a 
 particular manner in this connection. It is not so much by ques- 
 tioning the patient as by analysis of the phenomena observed, and 
 particularly cerebral symptoms, that the physician recognizes this 
 intoxication. We may repeat, however, that alcohol acts not only 
 upon the nervous system, but causes important lesions in the viscera 
 and particularly in the liver. We are thus led to investigate the role 
 of visceral affections upon the course of infections and their impor- 
 tance from a prognostic standpoint. 
 
 Role of Previous Visceropathies. As has already been stated, the 
 lesions of the heart do not markedly aggravate the prognosis. Con- 
 trary to what might be supposed, a chronic endocarditis seldom forms 
 the focus for a new cardiac localization. The prognosis depends, not 
 upon the extent or the nature of the valvular lesion, but upon the 
 condition of the cardiac muscle and the influence which its disorders 
 may have exerted upon various organs. Hence, chronic myo- 
 carditis renders prognosis more unfavorable than an aortic or mitral 
 les'on. 
 
 Lesions of the lungs, aside from tuberculosis, may, when they 
 disturb hematosis, hinder oxidation. They have also the inconveni- 
 ence of disturbing the action of certain therapeutic methods. Baths, 
 even when lukewarm, are very badly borne by emphysematous sub- 
 jects. Finally, when pulmonary lesions influence the heart, they 
 produce through this organ visceral disturbances the importance of 
 which we are about to consider. 
 
DIAGNOSIS AND PROGNOSIS OF INFECTIOUS DISEASE8. \ 
 
 Lesions of the kidneys notwithstanding thai they hinder organic 
 depuration, do nol render prognosis very unfavorable. No doubl we 
 often see a Bright's patienl succumb to an Lnfectiou complication, 
 suppuration, erysipelas, or pneumonia) bu1 this is al the last period. 
 When the individual is still resistanl he endures well an intercurrent 
 infection, notably erysipelas. Lesions of the liver are of greater con- 
 sequenee, bni we ninsi make an importanl distinction analogous to 
 Mint which we luive :i.dinii led with reference to the heart. It U nol 
 the extent or the topography of the sclerotic lesions, bu1 the condi- 
 tion of the hepatic cells thai is to be considered. A hypertrophic 
 biliary sclerosis does not prevenl the favorable evolution of erysip- 
 elas; an atrophic sclerosis renders the prognosis quite serious The 
 same is true of diffuse steatosis of the liver, as may be observed in 
 alcoholic individuals. The lesion of I lie cells explains the develop- 
 ment of nervous accidents, notably delirium tremens, and accounts 
 for the fatal termination. It is well to bear in mind, however, thai 
 hepatic lesions, even when extensive, sometimes remain latent. < m 
 the occasion of an intercurrent infection symptoms of hepatic insuf- 
 ficiency may become manifest. Affections of the stomach and intes- 
 tine may favor or hinder various infectious lesions. Hence, the great 
 service of gastrointestinal antisepsis in the therapeutics of the most 
 varied infections. It may also be stated that predisposition plays a 
 very important role in the development of grave nervous manifesta- 
 tions, and thus accounts for the persistence or the appearance of 
 certain disorders which may persist after recovery. 
 
 General Rules of Prognosis. It is evidently impossible to lay 
 down general rules of prognosis. We have mentioned the principal 
 questions which the clinician has to solve. We may explain the 
 method by an example. Let us suppose that we are dealing with a 
 case of pneumonia. Examination of the lungs is of prime importance 
 for diagnosis, but not so for prognosis. It is undoubtedly interesting 
 to know the extent of the hepatized zone, which may be judged by 
 the extent of the tubal murmur: but a more important element to 
 be considered is the condition of the parts surrounding the morbid 
 focus and the extent and intensity of concomitant congestion. The 
 other organs are to be considered more than the lungs. Examination 
 of the urine, of the liver, and especially of the heart, is of chief 
 importance in the diagnosis. An excessive acceleration of the heart- 
 beats, their weakness, and the appearance of fetal rhythm must guide 
 both prognosis and therapeutics. Moreover, we must determine the 
 
640 INFECTIOUS DISEASES. 
 
 constitutional ground upon which this pneumonia evolves, because, 
 with the same lesion and with the same influence of the lesion upon 
 the other organs the prognosis differs according as the case is that 
 of a young or old, robust or debilitated, temperate or alcoholic indi- 
 vidual. 
 
 When all these problems have been solved the task of the physi- 
 cian is not yet over. Prognosis must answer the following three 
 questions: 1. What will be the termination of the present disease? 
 2. What is its bearing upon the future of the patient? 3. Of what 
 importance is it for his descendants? It should, therefore, be deter- 
 mined whether the disease will be cured without leaving any appre- 
 ciable traces and whether some disturbances will persist in conse- 
 quence. It should be decided whether relapses or recurrences are 
 apt to take place, and whether they can possibly be guarded against. 
 It should also be predicted whether there will be any sequela? in the 
 remote future, or whether the descendants of the patient will be liable 
 to degeneration or sickness. Along with the prognosis of the individual 
 the prognosis of the race must be laid down. Then, and then only, 
 has the physician answered all the questions which incessantly meet 
 him on confronting each patient. 
 
 In establishing the rules of prognosis we have depended upon quite 
 simple clinical procedures. As a matter of fact, laboratory proced- 
 ures are in this respect of little importance. It was for a time believed 
 that bacteriology would supplant clinical observation. The study 
 of diphtheria led to the erroneous conclusion that examination of 
 cultures enabled one to determine the gravity of angina, even in the 
 absence of clinical observation of the patient. If the diphtheria was 
 found to be uncomplicated, and if the bacillus developed upon the 
 serum medium was not too long, the prognosis was favorable. If, 
 on the contrary, the bacillus was long and mixed with numerous 
 streptococci, the prognosis was grave. Although such correspon- 
 dence may at times be observed, it is far from being the rule, and 
 cannot replace examination of the sick or even modify the prognosis 
 based upon clinical observation. We likewise believe that no prac- 
 tical information can be derived from inoculations into animals. 
 Apart from the difficulties of the method, the results are too variable 
 to be taken as a basis of prognosis. A microbe virulent for man not 
 infrequently proves inoffensive for animals, and vice versa. Finally, 
 P. Courmont has recently proposed an ingenious method of serum 
 prognosis based upon the intensity of the agglutinating reaction. 
 
DIAGNOSIS AND PROGNOSIS OF INFECTIOUS DISEASES, 04] 
 
 This method is evidentlyveryinteresting and perfectly rational, ince 
 it is founded upon the appreciation of the organic reaction again I 
 the infection, but it has thus far been applied to typhoid fever alone, 
 and while it may render some service, it is, like all other laboratory 
 procedures, loo complex and delicate to enter into currenl practice. 
 
 we, therefore, conclude thai prognosis even more than diago 
 should be based upon simple procedures, upon an attentive exam- 
 ination of the patient, and minute and complete amly i of the di-- 
 turbances which he presents, As for diagnosis, so for prognosis: Jt 
 is not by a sort of divining power Ihnl the physician succeeds in 
 solving the problems presenting themselves with each case, but 
 simply by a profound study of pathology and long clinical experience. 
 
 4L 
 
CHAPTER XXII. 
 
 THERAPEUTICS OF INFECTIOUS DISEASES. 
 
 General Considerations on the Therapeutics of Infections. Toxic and Therapeutic 
 Equivalents of Medicines. Action of Medicines upon Normal and Infected Indi- 
 viduals. Principal Therapeutic Methods Employed in Infections. Antiseptic 
 Method. Phvsical Agents. Chemical Antiseptics. Determination of the Antiseptic 
 Power of Medicines. Choice of Antiseptics. Antisepsis of the Skin. Antisepsis 
 of the Genital and Urinary Organs. Antisepsis of the Mouth and Nose. Treatment 
 of Purulent Rhinites. Antisepsis of the Respiratory Passages. Antisepsis of the 
 Alimentary Canal. Importance of Insoluble Antiseptics. Antisepsis of Serous 
 Membranes. Intestinal Antisepsis. Employment of Peroxide of Hydrogen. 
 General Antisepsis. Antitoxinic Method. Specific Medication : Cinchona, Mercury, 
 Iodine, and Salicylic Acid. Bacteriothcrapy. Employment of Sterilized Cultures of 
 Streptococcus and B. prodigiosus. Attempts in Cancer and Eupus. Tuberculin. 
 Mallein. Serumtherapy. General Principles. Various Applications of Serum- 
 therapy. Serumtherapy against Cholera, Colon Bacillus, Diphtheria, Leprosy, 
 Glanders, Bubonic Plague, Pneumococcosis, Proteobacillosis, Pyocyanobacillosis, 
 Staph}dococcosis, Streptococcosis, Puerperal Fever, Tetanus, Tuberculosis, Typhoid 
 Fever, Eruptive Fevers, Vaccinia, Variola, and Hydrophobia. Prophylactic Injec- 
 tions of Serum. Accidents Ascribable to Serumtherapy : Cutaneous and Articular 
 Manifestations; Fever; Albuminuria, Hemorrhages, and Nutritional Disturbances. 
 Post-serum Therapic Hysteria. Prognosis of Serumtherapic Accidents. Mode of 
 Action of Therapeutic Serums. Conclusions. 
 
 By their natural evolution, acute infections tend toward recovery. 
 The duty of the physician is to observe the procedures resorted to 
 by nature, and, thus inspired, to direct the morbid reactions and 
 stimulate or restrain them, as the case may be. 
 
 The organism endeavors to destroy and expel infectious germs and 
 to neutralize and eliminate toxins. Similarly our therapeutic meas- 
 ures should be directed to the accomplishment of these four purposes. 
 Various procedures which not infrequently differ from those em- 
 ployed by nature may, however, be utilized in therapeutics. 
 
 To combat the animate agent which gives rise to infection is to 
 practise etiological medication. To deal with the toxins through 
 which the morbific germ acts is to practise pathogenic or physio- 
 logical therapeutics, as the case may be. 
 
 Etiological medication is the application of the old adage : Sublata 
 causa eff edits tollitur. It finds its formula in the antiseptic method. 
 The ideal would be the possession of substances which would destroy 
 
THERAPEUTICS OF INFE0TI0U8 DISEASE $43 
 
 fche germs and I"' inoffensive for the patient. Unfortunately, here 
 is fche stumbling-block. Neverthele . il ii po ible, with certain 
 precautions, to realize antisepsis in surface wounds and at time in 
 fistulous tracts. Kvcn in wounds, certain anti eptic exeii an irritant 
 action. They diminish the resistance of the cells, and, in spite of 
 their incontestable action upon the microbe, they favor rather than 
 hinder infection. At present , therefore, the tendency i to substitute 
 asepsis for antisepsis, and, when antiseptic substance! are employed, 
 care is taken to use weak solutions. Willi these precautions the 
 results are often satisfactory, provided, however, the antiseptics are 
 frequently changed. When any one of them is used for ;i long period 
 of time, the action is weakened through habit. 
 
 The abortive method, which is calculated to arresl ;ni infection at 
 its beginning, belongs to the antiseptic method, and it bs probable 
 that specific medication should also he included in ih«' 3ame group. 
 
 We are acquainted with certain substances which aires) the course 
 of certain infections. It is hardly necessary to mention the action 
 of quinine in malaria, of mercury and the iodides in syphilis, and of 
 the salicylates in rheumatism. The germicidal serums also belong to 
 this group. They represent the specific antiseptics par excellence, 
 possessing a selective action in destroying certain microbes and being 
 powerless against allied germs. 
 
 The microbe, as we have repeatedly stated, is not the sole cause 
 of an infectious disease. Auxiliary and predisposing causes often 
 come to its assistance. The therapeutist must take them into con- 
 sideration. His method is equally etiological when he struggles 
 against the various conditions which favor, maintain, or aggravate 
 infection. He can fulfil therapeutic indications by means of diet, 
 hygiene, and at times through special medication or surgical inter- 
 vention. Furunculosis ma}- be cured by combating the digestive 
 disturbances which produce or sustain it: suppuration may be 
 arrested by extirpating the foreign body which is found in the mor- 
 bid focus. While in these cases medication is not directed against 
 the primary cause, it none the less deserves to be considered as 
 etiological medication . 
 
 Pathogenic medication is that which combats the harmful action 
 of the pathogenic agent upon the organism. Bacteria act mainly by 
 their toxins. Therefore, all treatment directed against bacterial 
 poisons we consider as pathogenic. In many cases, however, patho- 
 genic treatment is confounded with physiological or naturalistic 
 
644 ISFECTIO US DISEASES. 
 
 treatment, which is intended to act against toxins, following the 
 processes which the organism emploj^s for the same purpose. The 
 distinction is in fact of little importance, for it may be said that the 
 struggle against infections conducted by the organism is carried on 
 on lines of pathogenic therapeutics. In support of this assertion it 
 will suffice to cite serumtherapy. We have stated above that certain 
 germicidal serums which destroy microbes, or at least exert upon 
 them a harmful action, represent an etiological method of treatment. 
 The serums which neutralize the effect of toxins are more important. 
 When we employ them against an infection, when, for instance, we 
 inject antidiphtheritic serum into a patient, we practise pathogenic 
 as well as naturalistic therapeutics — pathogenic, because we combat 
 the mode of action of the cause; naturalistic, because we are guided 
 by the reactionary mode of the diseased organism. In fact, we know 
 that, in order to combat the microbic poison, the organism secretes 
 an antitoxin. Through the agency of therapeutics we furnish to the 
 organism, from the very start of the disease, the protective substance 
 which it needs. We realize sooner what the organism would realize 
 later. Thus we save time by arresting bacterial intoxication at a 
 moment when its effects are still reparable. 
 
 It is not the bacterial poisons alone, however, that are to be 
 reckoned with in infections. The synergy which unites all the parts 
 of the organism spreads the disturbances throughout the entire 
 economy. Hence the secondary autointoxications, which should 
 never be lost sight of. In many cases procedures directed against 
 these poisons are nearly the same as those employed against toxins. 
 In fact, an attempt may be made to neutralize the noxious substances 
 formed by the organism or to stimulate the organs charged with the 
 function of destroying them, or an effort may be made to favor their 
 elimination. 
 
 In order to neutralize the autogenic poisons the oxidizing method, 
 which seems to act upon the microbic as well as upon the animal 
 toxins, is generally employed. When it is desired to stimulate the 
 organs concerned in the destruction of poisons, use should be made 
 of various substances capable of stimulating the cells, notably those 
 of the fiver. The role played by alimentation has already been 
 referred to. It will suffice to add that ether, in small doses, exerts 
 a very manifest action upon this gland. 
 
 The liver acts upon animal and certain microbic toxins, and, in 
 addition, possesses the power of destroying a great number of bac- 
 
THEBAPEUTI08 OF INFECTIOUS DISEASES. 646 
 
 fceria. Thus the many indications to which fchi therapeutic method 
 
 responds are evidenl . 
 
 The same complexity in effect appear r ith regard to elimination. 
 The simplest procedure seems to be represented by blood-letting. 
 The flow of the blood carries away a certain amounl of toxins. Jn 
 reality, however, the action of blood-letting is very complex, beci 
 at the same time thai the constitution of the blood is modified, the 
 exchanges .-ire slimuhinl and the work of the heari i- diminished. 
 Blood-letting docs noi, therefore, represenl a simple antitoxic 
 method. 
 
 The elimination of toxins and, coincidently, microbes may like 
 be favored by stimulating the emunctories, the digestive tract, the 
 skin, and, particularly, the kidneys. Lavage of the stomach and 
 intestine, the administration of emetics and purgatives serve to <-.irvy 
 away the noxious elements which originate in the alimentary canal 
 or are thrown into it. Certain drugs may increase the activity of the 
 emunctories. Sudorifics, diuretics, and tepid beverages are often 
 employed. In the treatment of acute infection-, however, physical 
 procedures are generally preferred. Heat or cold are called into play, 
 as the case may be. Dry heat favors sweating. Moist heat stimu- 
 lates or quiets the nerves. Lastly, a cold bath acts not so much by 
 dissipating the heat of the body as by mochTying the dynamic state 
 of the organism by means of the nervous reactions to which it gives 
 rise. It acts upon the general nutrition, upon the activity of the 
 liver, and especially upon the urinary secretion, which it increases 
 considerably. 
 
 It was hoped for a time that it would be possible to effect rapid 
 depuration of the organism by intravenous or subcutaneous injec- 
 tions of artificial serum. While more profound study has demon- 
 strated the excellent effects of this form of medication in the treat- 
 ment of acute infections, it has likewise established that its action 
 is very complex and that it affects the nervous system and general 
 nutrition rather than the emunctories. 
 
 It is thus seen that most of the procedures above indicated are far 
 less simple than would at first appear. They act mostly upon the 
 organism and stimulate the general reactions. The injections of 
 antitoxic serum or salt-water give rise to cellular proliferations which 
 must favor the defense of the organism. Therefore, not only humoral 
 modifications are produced, but the figurate elements are likewise 
 acted upon. Besides the general reactions of the organism, the local 
 
646 INFECTIO US DISEASES. 
 
 reactions which appear at the point invaded by pathogenic agents 
 must be considered. 
 
 According to circumstances, local inflammation must be stimu- 
 lated, checked, or diverted. Even acute manifestations may be stim- 
 ulated. Thus, one of the best treatments of erysipelas or phlegmons 
 consists in very hot applications. The reaction of the organism is 
 thus increased and, consequently, rendered more rapidly efficacious. 
 The phlogistic method is far oftener resorted to in the case of torpid 
 lesions. Certain suppurating foci, certain tubercular lesions, or 
 ulcerations of any description, are treated by hot applications, scari- 
 fications, and cauterizations. These procedures bring about recovery 
 by awakening an inflammation which had prematurely ended. In 
 other instances this effect is secured by means of toxic substances. 
 Potassium canthariclate and tuberculin stimulate atonic tubercular 
 lesions. Or w r e may act by producing a microbic inflammation. We 
 have sufficiently studied this question in connection with microbic 
 associations and shown notably the curative role of erysipelas. 
 
 In cases in which local reaction is too intense, it is evidently 
 necessary to moderate inflammation. This is particularly indicated 
 w r hen the lesion occupies an important organ and threatens life by 
 disturbing its function. It is usual to apply refrigerants and espe- 
 cially ice continuously over the cardiac region, the abdomen, and 
 the head in cases of pericarditis, peritonitis, or meningitis, respec- 
 tively. Peri-inflammatory or pre-inflammatory congestion is also 
 combated by blood-letting, antiphlogistics, and vasomotor medi- 
 cines. While nitrites are utilized to stimulate reactions, vasocon- 
 strictors, such as ergotin, are employed to restrain them. Finally, 
 a derivation may also be brought about. When an inflammation is 
 too intense, a revulsion at a more or less distant point can be induced. 
 This may sometimes be in the area of the skin corresponding to the 
 diseased region, where thermocauterization or mustard plaster is to 
 be applied. On other occasions the digestive canal may be acted 
 upon, for example, by means of purgatives. Thus a sort of metas- 
 tasis is artificially produced. 
 
 We cannot, therefore, in an exclusive manner assert that reactions 
 must be combated or stimulated. It is only necessary to remember 
 that inflammatory actions are always useful. They represent a 
 means of defense. It is to be noted, however, that their intensity 
 may exceed the object. We may then conclude that reaction must 
 sometimes be combated, often stimulated, and always directed. 
 
THERAPEUTICS OF INFECTIOUS DISEA8E8. <;}? 
 
 Although the medications, the general laws of which we have jusl 
 indicated, are fche most rational, ymptomatic therapeutic mu • not 
 be despised. The latter consists simply in remedying immediate 
 accidents, in combating certain disturbance without reascending to 
 their cause or point, of departure. Although it musl frequently be 
 considered as an acknowledgment of our ignorance, this method is 
 at limes the only possible and even the only admissible one. When 
 we are confronted by accidents which threaten lifewe musl resorl to 
 urgent medication directed againsl the disorder observed without 
 looking for its origin. When the physician is called to the bedside 
 of a patient who is suffocating, and he has recognized by the char- 
 acters of respiratory embarrassment that i1 is dependenl upon laryn- 
 geal stenosis, his lirsi thought should be to re-establish the coin 
 the air and immediately perform tracheotomy. Be may subse- 
 quently investigate the cause of the stenosis. 
 
 Symptomatic therapeutics mayserve as an auxiliary, and i- then 
 perfectly justifiable. A patient suffering from syphilitic cephalalgia 
 must receive specific treatment. As, however, the latter requires 
 several days to produce its effects, symptomatic medication is at the 
 same time to be resorted to in order to relieve the nocturnal exacer- 
 bations of pain and procure rest to the sufferer. To this end, along 
 with 60 to 90 grains (1 to 6 grams) of potassium iodide directed to 
 the syphilitic element, some hypnotic should be prescribed to relieve 
 the headache. 
 
 It is perfectly rational symptomatic medication to prescribe opium 
 for cough, atropine for sweating, enemas or purgatives for constipa- 
 tion, and analgesics for pain. In all these cases symptomatic medi- 
 cation assists therapeutics. It is, therefore, perfectly justifiable. On 
 the other hand, however, it is an avowal of our impotence if we are 
 contented with treating a symptom because we are unable to recog- 
 nize its mechanism or trace it to its cause. 
 
 Among the symptoms which most frequently call for treatment, 
 fever deserves special mention. The rise of temperature is painful 
 for the patient, it causes anxiety to the family, and preoccupies the 
 mind of the physician. Apprehension is felt that hyperthermia will 
 give rise to serious accidents if too intense and allowed to persist. 
 Moreover, since the use of the thermometer has become a daily 
 practise, it is one of the disturbances which is most readily detected. 
 There is, therefore, an inclination to direct all efforts against it. This 
 inclination is expressed by the introduction into therapeutics of a 
 
648 IXFECTIO US DISEASES. 
 
 prodigious number of febrifuges. But it seems to be demonstrated 
 to-day that the cellular lesions which were once attributed to fever 
 depend rather upon the toxic cause which engenders fever, and that 
 hyperthermia is, in reality, not so dangerous. At any rate, most of 
 the febrifuges, excepting specific ones, act upon the mechanism and 
 not upon the cause. As a rule, they hinder salutary reactions, 
 diminish oxidations, and consequently exert an unfavorable in- 
 fluence. Exception is to be made only of cold bathing, which alone 
 is rational, since it lowers the temperature by abstracting heat. In 
 connection with pathological physiology, we have shown that, in 
 fever, the dissipation of heat is increased. Cold bathing further 
 increases and thereby completes the work of defense undertaken by 
 the organism; it thus enters into the domain of natural medication. 
 
 General Rules of Therapeutics in Infections. The therapeutics 
 of infectious diseases is based upon clinical observation and experi- 
 mental research. Formerly attempts were first made upon diseased 
 men. The old physicians, led by theoretical ideas which were often 
 erroneous, or assisted b}^ some happy coincidence, tried a great num- 
 ber of medicinal substances. Some of these, having proved really 
 efficacious, are still employed. At times we utilize them without 
 knowing exactly by what mechanism they act. Tradition having 
 established their role, we cannot blame empiricism directing this 
 course of action. Sometimes experimentation immediately demon- 
 strated the mode of action of the medicine or explained and justified 
 its emplojmient. Formerly experimentation upon animals followed 
 the application to man. At the present day therapeutics must adopt 
 a reverse course and always begin with experimental study. The 
 latter informs us as to the toxic and pharmacodynamic action of the 
 medicine. It therefore has a double object. 
 
 In order to determine the toxic equivalent of a substance, it is 
 necessary to experiment upon animals of different species. We can- 
 not be too cautious when acting upon man. The fatal close is deter- 
 mined by intravenous injection, and for certain medicines the dose 
 which is immediately fatal and that which is ultimately so should 
 be ascertained. It is necessary to know that certain substances, 
 even when injected into the veins, produce no, or only slight, dis- 
 turbances. If, however, the dose is increased, the animal dies a few 
 seconds after injection or even while the toxic substance is still being 
 introduced. With certain substances, if the intravenous injection is 
 arrested at the moment when the fatal dose is approached, the 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 649 
 
 symptoms disappear and the animal recovers. However, auch i- not 
 always the case. There is often a period of latency during which 
 the animal appears to be in good health. After a variable length 
 of time disorders are produced and terminate in death. The poison 
 did not act immediately, and perhaps it underwenl previous b 
 formation within the organism, lie thai at it may, the do e which 
 is tardily fatal is often considerably smaller than the one immediately 
 fatal, and, for the physician, this is a poinl of greaf consequence. 
 
 As intravenous injection of medicines is seldom employed, it is 
 indispensable, after studying the toxicity of the substance* injected 
 into the blood, to investigate their action when they are introduced 
 by other channels, notably beneath the skin or into the alimentary 
 canal. The role of absorption, the influence of transformations which 
 may occur within the gastrointestinal cavity, in contact with ali- 
 ments, secretions, and microbes which multiply there, may modify 
 the composition and consequently the action of medicine-:. When 
 absorption has taken place, the substance, before reaching the points 
 upon which it acts, passes through certain glands which may further 
 modify its composition or its action. Among the latter are the liver 
 and lungs. 
 
 These are sufficient reasons for multiplying the experiments and 
 injecting the poison by the most varied channels. It does not suffice, 
 however, simply to notice the effects of a single dose. In general, 
 the physician prescribes a medicine for several days in succession. 
 The experimenter must, therefore, administer the substance for a 
 certain length of time, and, if no disturbance results, he must not yet 
 declare the substance to be harmless. He must observe the animals 
 and kill some of them in order to learn whether there are pro- 
 duced in their organs lesions unexpressed by any symptom and 
 which can be determined onty by histological examination. 
 
 These preparatory studies are very tedious and delicate. It seems 
 to us, however, that they are indispensable when it is desired to 
 make therapeutic application to human beings. It is to be noted, 
 however, that these first investigations teach us only the dangerous 
 and harmless doses. After determining these first points, namely, 
 after solving the toxicological problem, the pharmacodynamic study 
 is to be undertaken. Assisted by all the modern scientific data, an 
 inquiry into the modifications of the medicine within the organism, 
 its channels of elimination, its action upon the fluids, tissues, and 
 organs ma}' be made. In this connection, chemical analysis on the 
 
650 INFECTIOUS DISEASES. 
 
 one hand, and on the other physiological analysis and, notably, the 
 graphic method, must intervene. 
 
 The rules just referred to are general rules applicable to all thera- 
 peutic studies. When the treatment of infections is reached these 
 rules require to be completed with some particular data. 
 
 Since we can produce in animals a great number of infectious dis- 
 eases we must no longer pursue our studies by operating upon 
 healthy but upon infected animals. 
 
 The necessity of investigations of this sort appears when it is 
 believed that a medicine capable of curing a disease has been found. 
 It is then necessary to inoculate a certain number of animals, some of 
 which are to be kept as controls and others to'receive the medicinal 
 substances. The results thus obtained are of great value, since 
 experimental infection is always simpler than a spontaneous infec- 
 tion. It is monomicrobic, while in man the disease often results from 
 an association of microbes. The treatment may be begun as soon 
 as is desired, while in spontaneous infection the first symptoms are 
 often belated and appear a long time after contamination. Lastly, 
 the use of control animals gives undeniable value to experimental 
 results, while in clinical experience we may clearly see what is pro- 
 duced as a result of the treatment, but we do not know what would 
 happen in case of abstention. 
 
 Nevertheless, we must not conclude that the successes are the 
 same in both cases, for the reason that clinical cases are complex, and 
 treatment is often commenced too late, or the organism is affected 
 by taints or previous lesions. Clinical observation must pronounce 
 final judgment, and, too often, it establishes an apparent antagonism 
 between practical application and experimental results. 
 
 When it is desired to determine the action of antimicrobic or anti- 
 toxic substances the pharmacodynamic action is often discarded 
 and an attempt is made to solve the following three problems : What 
 is the action of the substance upon the microbe or the toxin outside 
 the organism? What is its toxic action upon the healthy animal? 
 What is its curative action upon the diseased animal — i. e., upon the 
 infected or intoxicated animal ? 
 
 The rules which govern the solution of the last two questions are 
 the general rules which we have already exposed. As to the first 
 problem, if the question concerns an antiseptic substance, it is cus- 
 tomary to investigate the effect of artificial media upon the vegeta- 
 
THERAPEUTICS OF INFECTIOUS DI8EA8ES. <;.,] 
 
 tive property of the microbe, [noculations into animals should be 
 next undertaken, for microbes which are o altered a* to no longer 
 develop in a culture bouillon may sometimes be still sufficiently 
 active to vegetate within the organism. On the other hand, microbes 
 which are incapable of overcoming the resistance of the economy may 
 still be able to live in inert media. The greal principle of atten- 
 uation of viruses is based upon this fact. 
 
 When antitoxic substances are under study, experimentation i- 
 the only method which reveals the modifications produced. The 
 toxin and the antitoxin are injected into the animals simultaneously 
 and successively. These principles are daily utilized in the study of 
 therapeutic scrums. 
 
 It is certain that the method furnishes excellent indications. 
 Although, in this case, experimentation approaches clinical obser- 
 vation as nearly as possible, the facts do not and cannot altogether 
 correspond. The experimental results obtained with serums are 
 always more brilliant than those observed clinically. The reason is 
 that clinical facts are always complex. Honce, even when a greal 
 number of specific serums have been prepared, it will still be neces- 
 sary to resort to medicines intended to palliate certain disturbances 
 and to combat certain accidents. 
 
 Unfortunately, the substances which are used in this case have 
 been studied only upon healthy animals. It would, therefore, be 
 interesting to repeat their study upon infected animals from the 
 double standpoint of toxicology and pharmacodynamics. It is m 
 sary, in fact, to determine whether the medicine has the same 
 toxic property in the diseased and the healthy animal, and whether 
 this toxicity is modified by the different periods of the disease. It is 
 also necessary to inquire whether the medicine always acts in the 
 same manner, whether infection does not modify its mode of action. 
 Here, we believe, is a large field open to experimenters. As few 
 researches have been made upon this point, we have believed it 
 would be of interest to study what becomes of the resistance of 
 animals through strychnine in the course of anthrax infection, and 
 then to undertake analogous researches with strychnine and chloral 
 in animals suffering from tetanus. From our experiments we may 
 draw the conclusion that chloral may be employed to palliate the 
 painful phenomena produced by tetanus, but it is not a truly cura- 
 tive medicine. 
 
652 INFECTIOUS DISEASES. 
 
 Antiseptic Method. 
 
 The object of the antiseptic method is to destroy the pathogenic 
 agents by acting directly upon them and indirectly by modifying 
 the organism. When it is incapable of destroying these agents, it 
 opposes their multiplication or hinders their harmful action. We 
 know at present that microbes act only by their soluble products. 
 The history of antitoxic substances which neutralize or diminish 
 the action of toxins may, therefore, be considered as supplementary 
 to the study of antiseptics. 
 
 Antisepsis by Physical Agents. The indications of antisepsis may 
 be realized by procedures of a physical order. As is known, heat is 
 the surest agent for destroying microbes. Unfortunately, although 
 it is daily employed for sterilizing inert substances, it is too difficult 
 to manage when applied to the living organism. While very hot 
 local applications hinder infections ; they accomplish this simply by 
 modifying circulation. They act upon the microbes in an indirect 
 manner. When, however, the lesion is well circumscribed, it is pos- 
 sible to destroy it by thermocauterization. Folliculites are thus 
 cured. If the lesion is extensive, a red-hot iron can be used, as is 
 done for certain phlegmons and gangrene. It is, perhaps, possible 
 to combat infections of serous membranes by very hot-water irriga- 
 tions. It is possible to inject into the peritoneum or the veins of 
 animals salt water at a temperature of 122° F. (50° C.) or 131° F. 
 (55° C.) without any inconvenience. We should not, however, rely 
 too much upon these different methods, since heat coagulates albu- 
 mins, and the minute particles thus formed protect the pathogenic 
 agents. Moreover, when it is intense, heat cannot be applied, except 
 to circumscribed points, and, consequently, it acts upon a very 
 restricted area of the diseased tissue. 
 
 There are certain viruses which are much more sensitive to heat 
 than the neighboring tissues. Thus the investigations of Dr. Aubert 
 show that 100.4° F. (38° C.) is sufficient to check the multiplication 
 of the bacillus of soft chancre. At a temperature of 104° F. (40° C.) 
 the microbe is killed. Hence, by employing this temperature, which 
 is not harmful for the tissues, we may rapidly cure a soft chancre. 
 A variant of this method consists in treating the lesion by means 
 of overheated air. 
 
 Microbes withstand cold far better than heat. Hence, cold appli- 
 cations, although they sometimes modify the vitality and the inflam- 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 853 
 
 matory react ions of I Ik: (issues, exerl no influence whatever upon 
 
 the pathogenic elements. When the germicidal action <>f the sun's 
 rays were revealed, the influence of lighl upon the cow e of infections 
 was investigated. The problem is complex, however, since the 
 action exerted upon the organism and upon the microbei i to be 
 taken into account, [nteresting attempts bave neverthelet been 
 made with Hie object of utilizing certain properties of sunlight. 
 Finsen has become the champion of Hie phototherapic method. An 
 attempt has also been m;idc In cause patienb suffering from variola 
 to sojourn in wards provided with red glass window.-. The results 
 have not been very encouraging. On the other band, quite remark- 
 able results have been obtained by treating lupus patients with coi- 
 orcd sun-rays. 
 
 Antisepsis by Chemical Agents. Chemical antiseptics are 
 trcmcly numerous, and certain amongthem were known and employed 
 in olden times. 1 In the days of Hippocrates wine and aromatic 
 oils and certain caustic iron and copper salts were employed for 
 washing wounds. The same substances were much used in the middle 
 ages. Later, cinchona powder, mercurial, arsenical, and astringent 
 preparations, as well as balsams and resins, came into use. 
 
 We must come to the time of Lister to find a true doctrine of 
 antisepsis, at least of surgical antisepsis. Lister, taking a> a basis 
 the works of Pasteur on fermentations, assumed that the air exer- 
 cised a noxious influence upon wounds by virtue of the germs which 
 it contained and deposited in the wounds. Therefore, making use 
 of carbolic acid, which was already employed by Lemaire, he washed 
 his hands with a 2\ per cent, solution, immersed his instruments in 
 a stronger solution (5 per cent.), washed the field of operation with 
 a strong solution, and during the operation directed upon the field 
 a spray of carbolic acid . He then introduced drainage tubes sterilized 
 by means of carbolic acid. Lastly, after covering the wound with 
 a protective bandage, he applied carbolized gauze and impermeable 
 mackintosh tissue. 
 
 At present the principles laid down by Lister are modified and his 
 procedures are abandoned. The germs of the air are not feared as 
 they w r ere formerly. The pathogenic agents present upon the skin 
 of the patient are more to be feared, and especially those found upon 
 the hands of the surgeon and his assistants. Therefore, the spray 
 
 1 Weiss. Contribution a letude des niethodes servant a determiner le pouvoir anti- 
 septique. Th&se de Paris, 1900. 
 
65-1 INFECTIOUS DISEASES. 
 
 was first done awaywith : next, the instruments and the dressings were 
 successfully sterilized by heat; then the use of antiseptics was grad- 
 ually abandoned, and in a word, asepsis was substituted for anti- 
 sepsis. This is at least what is done in surgical operations when 
 diseased but not infected parts are operated upon. When, on the 
 contrary, parts invaded bj' pathogenic germs are dealt with, anti- 
 sepsis is still utilized. It has been recognized, however, that strong 
 antiseptics are to be avoided, because of their caustic action, which 
 is more harmful to the tissues than to the microbes. In most cases 
 it is sufficient to resort to profuse lavage with boiled water, which 
 acts mechanically by carrying aw^ the germs and their toxins as 
 well as the degenerated cells contained in the morbid focus. 
 
 "While antisepsis has lost its first importance in surgery, it is still 
 held in great esteem in medicine. Attempts have been made to kill, 
 at least partially, the germs swarming in the digestive canal and 
 those which may invade the respiratory or urinary apparatus. Even 
 general antisepsis of the organism has been aimed at by some prac- 
 titioners. It is, therefore, important to have at one's disposal a 
 certain number of antiseptic substances. 
 
 An antiseptic must fulfil certain general conditions and, according 
 to the use for which it is destined, possess particular properties. The 
 general properties of all antiseptics are the following : to be harmful 
 for the morbid germs ; to be harmless for the animal cells with which 
 it comes in contact ; not to form with the organic elements combina- 
 tions which render them inoffensive for microbes; not to coagulate 
 albumins the particles of which protect the bacteria. 
 
 The particular properties may be diametrically opposed according 
 to the case. According as we have to sterilize a closed cavity or a 
 surface, to act upon a limited area, or, on the contrary, to extend 
 the germicidal action to distant parts, to treat the alimentary canal, 
 the urinary or respiratory apparatus, we must employ soluble or 
 insoluble, diffusible or non-diffusible, liquid or solid, pulverulent or 
 volatile substances. 
 
 The problem which might at first view appear quite simple is, 
 therefore, very complex. We must study antisepsis itself — i. e., we 
 must determine the action of each substance upon microbes; then 
 establish its toxic equivalents and investigate the therapeutic indica- 
 tions to which it may respond. 
 
 The determination of the antiseptic power of a substance is not 
 as easy as may be believed. The results vary according to the 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 656 
 
 microbe which is operated upon and the condition tinder which we 
 are placed. Et is evident thai the ame amounl of an antiseptic will 
 have different effects according as it acts upon more 01 itive 
 
 species or upon cultures provided with or deprived o Finally, 
 
 for the same culture, we must take into account the number of 
 microbes upon which the effects of the antiseptic ubstanc* 
 exerted. 
 
 In order to study the ad ion of an antisepl ic, many exj erimei 
 add a certain quantity of i1 to a culture medium, and then culti 
 in the latter a particular bacterium. Ii is too often forgotten, how- 
 ever, that, under these conditions, the solid or !i<|ui<l medium em- 
 ployed has riot a fixed constitution, and thai the results may vary 
 from one day to another. Ii is, therefore, better to maki 
 solutions of constant composition, for instance, a mineral solution to 
 which a pure peptone is added. The medium being definite, the 
 addition of the antiseptic substance may produce a precipitate which 
 annihilates the action of the germicidal substance, or the latter may 
 enter into a more or less stable combination calculated to diminish 
 its power or to reduce the nutritive property of the medium. Ii is 
 also to be remembered that the surrounding temperature exerts an 
 important influence upon the development of the microbe. At a 
 certain degree it favors its vegetation; as it advances, however, it 
 increases the germicidal action of the antiseptic. Thus, to cite only 
 one example, Chauveau and Arloing have shown that a 3 per cent. 
 solution of carbolic acid exerts no action upon the bacillus of gaseous 
 gangrene when its action lasts for twenty-four hours at a temperature 
 of 59° F. (15° C). At 96.8° F. (36° C.) it sterilizes the medium within 
 six or eight hours. 
 
 The results also vary acording as the germs operated upon are 
 dry or moist. In the former case resistance is much greater. Dr. 
 Chamberland thinks that the difference of action is due to the time 
 necessary to moisten the dried microbes. In order to avoid these 
 various causes of error another method is frequently resorted to. 
 Platinum threads, silk threads, pieces of glass, paper, or linen are 
 dipped into the culture to be studied. These are then exposed to 
 antiseptic vapors or immersed in the antiseptic fluid. After a vari- 
 able time the objects thus impregnated with cultures are washed 
 with sterilized water and placed in a nutrient medium. 
 
 This method, which at first appears as simple as it is exact, in 
 reality is exposed to grave errors. In the first place, when a culture 
 
656 INFECTIOUS DISEASES. 
 
 is spread upon any object whatsoever, the distribution is not uniform. 
 There are thicker parts which do not undergo the action of the 
 antiseptic, except in their superficial zone. Moreover, in spite of 
 prolonged washing, we can never be sure of having removed all the 
 antiseptic. A quantity sufficient to prevent multiplication may 
 remain. Finally, Drs. Chamberland and Fernbach have shown that 
 the results vary according to the objects used in the experiments. 
 Germs spread upon paper die more quickly than those distributed 
 upon glass, while those that are found upon linen resist for a still 
 longer period of time. E. Weiss advises addition of the antiseptic 
 to a bouillon culture, then to take from the latter a small drop and 
 put it in a large amount of fresh bouillon. The trace of antiseptic 
 thus introduced is insignificant. This method is in fact sufficiently 
 exact and has the advantage of great simplicity. 
 
 When the substance to be studied is insoluble in culture media 
 we are obliged to dissolve it previously in some liquid like alcohol 
 or ether. The results then will vary according to the nature of the 
 solvent. Finally, when it is volatile, we must take a series of pre- 
 cautions in order to prevent evaporation during the experiment. 
 
 These few considerations show how complicated the problem 
 which is apparently so simple becomes when we desire to study it 
 with some accuracy. We must also remember that microbes become 
 habituated to the substances that are harmful to them, so that by 
 making cultures in series in media charged with antiseptics the 
 multiplication of the germs becomes progressively easier. 
 
 An antiseptic substance produces quite different effects according 
 to the amounts employed. These effects may be classified in the 
 following order: In large doses, sterilization, viz., death of the mi- 
 crobes, occurs. Next, when the doses gradually diminish, infertility 
 of the medium occurs — i. e., the microbe remains living, but it cannot 
 multiply; when, however, it is transferred to another medium, it 
 again multiplies. In another class of cases the microbe develops, but 
 the colonies appear tardily and are small in number. At the same 
 time the functions are disturbed. The pathogenic agents become 
 attenuated, and we have already shown that the addition of anti- 
 septics represents a method for the transformation of viruses into 
 vaccines. At all events, it is very easy to appreciate the functional 
 modifications produced by antiseptics in studying the chromogenic 
 bacteria. Amounts which permit multiplication prevent the appear- 
 ance of pigment. 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 
 
 657 
 
 finally, there is a result analogous to facl ob erved when 3tud 
 the action of poisons upon animals. Anti epticc in very minute 
 amounts, far from hindering the function of microbe . stimulate it 
 to a notable degree. We have shown, for example, thai a tra< 
 corrosive sublimate favors the production of red pigmenl by the 
 B. prodigiosus. 
 
 The experiments performed with ;i view to determine the value of 
 
 antiseptics ;irc innumerable. In older to fix the ideas, il will suffice 
 
 to borrow some figures from Mequel's scale of antiseptic power. Thb 
 author has investigated the amounl of antiseptic capable of opposing 
 the putrefaction of one quart (litre) of bouillon. We shall mention 
 
 only the substances most l'rc<|ucn!ly used in medicine: 
 
 Eminently antiseptic substance; 
 
 Very highly antiseptic substance! 
 
 Highly antiseptic substances 
 
 Moderately antiseptic substances 
 
 Slightly antiseptic substances 
 
 Mercury biniodide 025 
 
 Silver iodide 0.03 
 
 Peroxide of hydrogen 05 
 
 Bichloride oi mercury .... 0.07 
 
 Silver nitrate . 0.08 
 
 I Ismic .'Hid chromic acids .... 15 
 
 Chlorine, iodine, cyanhydric acid _'." 
 
 Bromi tie, iodoform o 80 
 
 Bromoform 0.7 
 
 Chloroform . 0.8 
 
 I lopper sulphate 0.9 
 
 Salicylic ami benzoic acids l.o 
 
 Picric acid ] .3 
 
 Zinc chloride [.9 
 
 Thymic acid 2.0 
 
 Sulphuric, nitric, and hydrochloric acids . 2 t«, .', 
 
 Carbolic acid 3.2 
 
 Potassium permanganate 3.5 
 
 Alum 4.5 
 
 Tannin 4.8 
 
 I \rscnious acid 0.0 
 
 ! Boric acid 7 .". 
 
 | Chloral hydrate 9.3 
 
 [Sodium salicylate 10.0 
 
 I Sulphuric ether 22.0 
 
 j Et hylic alcohol 95.0 
 
 I Potassium iodide 140.0 
 
 | Glycerin 225.0 
 
 [ Sodium chlorate 400.0 
 
 It is well to add to this list oils the properties of which were 
 already known to the ancient world, and were employed especially 
 for purposes of embalming. We are indebted to Dr. Chamberland 
 for very interesting researches on their antiseptic action. According 
 to this scientist, six of them are the leading oils. viz.. the essence 
 of origanum. China cinnamon, Ceylon cinnamon, Angelica, vespetro, 
 and geranium. 
 
 Behring has studied the relationship between the toxic and anti- 
 septic power of bacillus anthracis, and has concluded that the relative 
 toxicity hardly varies. It oscillates around the figure 6. That is to 
 
 4-2 
 
658 INFECTIOUS DISEASES. 
 
 say, in order to kill one kilogram of animal the substance required 
 is six times smaller than is required for sterilizing one quart (1000 
 cubic centigrams) of liquid. Here are a few figures given by him 
 and which may present a certain interest from a practical standpoint: 
 
 Antiseptic Power. Toxic Power. Relative Toxicity. 
 
 Carbolic acid. 1.7 gr. 0.27 gr. 6.6 
 
 Corrosive sublimate . . . .0.1 gr. 0.017 gr. 5.8 
 
 Chlorohydrate of quinine . . . 0.S gr. 0.17 gr. 4.7 
 
 Mercurocyanide of potassium . . 0.017 gr. 0.003 gr. 5.6 
 
 Argent ocyanide of potassium . . 0.02 gr. 0.003 gr. 6.6 
 
 Aurocyanide of potassium . . . 0.04 gr. 0.006 gr. 6.6 
 
 In determining the toxic properties possessed by antiseptics we 
 must not be contented with the results obtained in animals. It is 
 likewise necessary to remember that man presents a peculiar sensi- 
 tiveness which varies from one subject to another. All antiseptics 
 may produce erythemata, a few may cause urinary disorders, as is 
 the case with carbolic acid, and lesions in the mucous membranes of 
 the mouth and large intestine, such as is the case with corrosive 
 sublimate. Without dwelling upon all these accidents, which are 
 well known and have often been described, 1 we shall cite an obser- 
 vation which shows the susceptibility of certain subjects to antisep- 
 tics. In consequence of a slight traumatism a young man was treated 
 with applications of a mild solution of corrosive sublimate. At the 
 end of fort3^-eight hours the arm was so red and swollen that it was 
 thought to be a case of erysipelas, and the sufferer was therefore sent 
 to our wards. We there corrected the diagnosis, and, remembering 
 that the skin already irritated by the application of some antiseptic 
 cannot well tolerate the use of other substances, we prescribed 
 simply application of boiled water. The symptoms improved quite 
 rapidly. We then vaccinated the patient, and before the inoculation, 
 we washed the arm with Van Swieten's solution. On the following 
 day we found the part of the skin which had come in contact with 
 the mercurial solution red and swollen, and, what was altogether 
 characteristic, the drops of the solution had flowed along the arm 
 and had marked their passage in the form of lines of small pyriform 
 plates of an intense red color. Thus, when an antiseptic is to be 
 employed the choice must be governed in view of the region to 
 which it is to be applied and according to the effect which is aimed 
 at, the microbe which is to be acted upon, and the special sensi- 
 
 1 To see notably the " These d'aggr6gation" of F. Brun. Des accidents imputables 
 a. l'emploi chirurgical des antiseptiques. Paris, 1886. 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 859 
 
 tiveness of the individual, if this is known by hif previou experi- 
 ence. It is also to be remembered thai it i- often advantage 
 
 to combine several antiseptic in one solution, for their i «>'■■■ er agaim > 
 I, ho microbes iiici-o;isos more rapidly than i- indicated by the 
 total of the components, while ju i the contrary if true a regards 
 thetoxicity. II is well to recall thai ho1 solutioni are more effective 
 and that it is often advantageous to add to the Liquid substances 
 which prevent coagulation of the albumins. Lastly, al theend of 
 a certain period of time, the antiseptic action seeme to I"- exhausted, 
 and some other substance musl then be employed. 
 
 These general rules will find their application in the rapid review 
 which we shall give of the antisepsis of various parts of the body. 
 In this exposition we borrow a greal number of documents from 
 Prof. Bouchard's lectures. 1 
 
 Antisepsis of the Skin. Antisepsis of the skin has long been 
 appreciated, and the ancient lawgivers laid stress upon the usefulness 
 of ablutions. At the present time the practitioner often utilize anti- 
 septic bathing. He sometimes employs naphthol water in the dose 
 of 10 drams for a bath of 200 quarts (40 grams in 200 litres) or a 
 bath with corrosive sublimate water. The use of this last sub- 
 stance has the inconvenience of requiring special bath-tubs. The 
 proportion is 2.50 to 5 drams (10 to 20 grams) of corrosive 
 sublimate mixed with the same amount of chlorhydrate of ammonia. 
 which makes a proportion of 0.05 to 0.1 per thousand. Baths 
 with corrosive sublimate are daily emploj'ed in our hospitals 
 for disinfecting the skin of convalescents. They may also be used 
 in the course of certain infections characterized by cutaneous mani- 
 festations. They are most frequently used in the treatment of 
 variola. In this infection, however, we give preference to naphthol 
 baths. Naphthol dissolved in alcohol should be poured into the bath- 
 tub. A bath lasting a quarter of an hour is given at the beginning 
 of the disease. Secondary infections are prevented in this way. 
 Antiseptic bathing is at present recognized to be the best treatment 
 of pustular variola. 
 
 Naphthol baths also render important service in cases of extensive 
 superficial lesions. The author employs them against the wandering 
 type of erysipelas as well as in furunculosis, which is so frequent in 
 consequence of certain infections, such as variola and. varicella. 
 
 1 Bouchard. Therapeutique des maladies infectieuses. Antisepsie, Pari-. 1889. 
 
660 IXFECTIOUS DISEASES. 
 
 It is hardly necessary to state that local baths may be prescribed 
 in cutaneous lesions upon the extremities. This manner of bathing 
 gives gratifying results in the treatment of panaris, lymphangites, 
 erysipelas, and phlegmons on the limbs. According to requirements, 
 the baths are given with corrosive sublimate, carbolic acid, or potas- 
 sium permanganate. In the intervals of the baths compresses dipped 
 in a slightly antiseptic liquid are applied to the affected parts. In 
 lesions with gangrenous or putrid tendency the author uses with 
 advantage compresses moistened with peroxide of hydrogen. Equal 
 parts of commercial peroxide of hydrogen and four per thousand 
 sodium bicarbonate solution are mixed; thus the fluid is neutralized, 
 and is then brought to six volumes by addition of four parts of water. 
 
 It should be remembered that antiseptics are not always well 
 borne by the skin, that they often give rise to intense and rebellious 
 dermatites, and that the local medicinal lesion is often the starting 
 point of an extensive and generalized erythema. In such cases an 
 application of another antiseptic only intensifies the inflammation, 
 and, by diminishing the resistance of the skin, favors the develop- 
 ment of secondary infections. Under such conditions use should be 
 made simply of sterilized compresses dipped in boiling water, poul- 
 tices, and in certain cases, salves prepared with perfectly neutral 
 vaseline. 
 
 Antiseptics applied to the skin act only upon the surface. In 
 certain cases they arrest infection of cutaneous glands. Thus, for 
 instance, applications of tincture of iodine often abort the develop- 
 ment of furuncles. Do they, however, act as antiseptics or as stimu- 
 lants? Better results are obtained simply with alcohol. In persons 
 who are subject to furuncles or acneic pustules in the neck, energetic 
 friction with some alcoholic tincture every morning is prescribed. 
 The results are generally very good. Alcohol renders valuable service 
 in the treatment of all small lesions of this kind. Thus absolute 
 alcohol saturated with boric acid is successfully employed against 
 folliculites, sycosis, furuncles of the auditory canal, etc. 
 
 In order to act upon the deeper parts of the epidermis, mechanical 
 procedures, such as friction and brushing, may also be resorted to. 
 This is currently practised in surgery for disinfecting the field of 
 operation. When infection occurs this procedure is no longer of any 
 use. It has, therefore, been thought that the antiseptic would better 
 penetrate if thrown in the form of jets. Thus carbolized spray is 
 employed in anthrax, and corrosive sublimate spray in erysipelas. 
 
THEBAPEUTI08 OF INFECTIOUS DI8EA8E8. 661 
 
 Antisepsis of the Genital and Urinary Organs. Anti ep i of the 
 genital organs occupied I lie attention of ancienl lawgivei at much 
 as ili;i,i, of i.lic skin. In the law of Mo e , purification after each 
 physiological or pathological flow or discharge w& pre cribed. Con- 
 finement, menstruation, and nocturnal pollution rendered the indi- 
 viduals impure. The law prescribed for the priesl bathing after 
 sexual intercourse. II is evidently as an antiseptic measure thai 
 certain religions have ordered circumcision. 
 
 At the present- day it is customary to wash the external genital 
 organs and to irrigate the vagina for purposes of cleanliness. The 
 rules which must govern the disinfection of the genital organ 
 almost the same as for the skin. For the treatmenl of balanitis in 
 man, injections are made between the foreskin and the glane penis, 
 but fluids containing alcohol should be avoided, since their contad 
 with the genital mucous membrane is very painful. Weak solutions 
 of potassium permanganate, corrosive sublimate, silver nitrate, pro- 
 targol, or a 20 per 1000 solution of liquid subacetate of lead are used 
 in most cases. In women, under pathological conditions, the vagina 
 is disinfected by injection of the same substances or by application 
 to the mucous membrane of gauze or cotton tampons. If the infec- 
 tion involves the uterus, antiseptics are more frequently employed. 
 According to the requirements of the case, the cervix of the uterus 
 may previously be dilated by means of a canula, and lavage given 
 with weak antiseptic solutions. In certain instances continuous irri- 
 gation is resorted to according to the method of Drs. Pinard and 
 Varnier. The substances most frequently employed are the bichloride 
 or biniodide of mercury, carbolic acid, and permanganate of potassium 
 in the proportion of 1 : 10,000. Mercurial salts often produce dis- 
 turbances which are easily overlooked because they are wrongly 
 attributed to the infection which is being combated. Thus, dysen- 
 teriform symptoms have sometimes been induced by mercurial 
 ulceration of the large intestine. 
 
 Antisepsis of the uterus and bladder may be practised according 
 to two different procedures : Medicinal substances may be injected 
 or ingested; in the latter case the medicine reaches the bladder when 
 eliminated through the urine. Antisepsis of the urethra is hardly 
 ever practised except in cases of gonorrhea. At The beginning of the 
 infection, the abortive method may be resorted to. This generally 
 consists in injecting a 1 or 2 per cent, solution of nitrate of silver. In 
 one-third of the cases this method proves successful. At a later stage 
 
662 rXFECTIOUS DISEASES. 
 
 injections are used, the formula? of which are innumerable. Recently, 
 however, they have been replaced by profuse irrigations with 1 4000 
 solution of potassium permanganate. These irrigations may be 
 prescribed from the very beginning of the disease, except when the 
 infection is particularly acute. In this instance the lips of the meatus 
 are swollen and the canal is hard. Then the first treatment must be 
 emollient. Later on, when the acute phenomena have subsided, the 
 chronic lesions quite often persist. Gonococci then multiply in the 
 prostate gland. Under such circumstances massage of the organ is 
 practised ; fifteen to twenty drops of a 2 per cent, solution of silver 
 nitrate or forty to sixty drops of a protargol solution of the same 
 strength are introduced. Finally, antisepsis of the urethra may 
 likewise be effected by medicated bougies. 
 
 Irrigations analogous to those employed for the urethra find appli- 
 cation in the treatment of vesical affections. Permanganate, pro- 
 targol, or simply boric acid are mostly used. These irrigations 
 act mechanically rather than chemically. A healthy bladder is only 
 exceptionally infected. In the great majority of cases cystitis 
 results from unclean catheterization in individuals in whom the 
 bladder empties itself poorly — i.e., in those who suffer from stricture 
 of the urethra and particularly from prostatic hypertrophy. Stag- 
 nation of the mine favors multiplication of the germs. Irrigations, 
 therefore, no matter what kind, have the great advantage of sup- 
 pressing the principal cause which induced and sustained the infec- 
 tion. 
 
 Antisepsis of the urinary passages, ureter, bladder, and urethra 
 may be effected by the administration of substances which may be 
 eliminated by the kidneys. Balsams, such as copaiba, cubebs, santal, 
 and turpentine, are daily employed for this purpose. Lastly, salol, 
 which is broken up in the intestine into carbolic and salicylic acids, is 
 also used. Elimination of the substances through the urine realizes 
 a slight antisepsis and renders valuable service in the treatment of 
 cystites. 
 
 Antisepsis of the Mouth. Antiseptic Treatment of Stomatites 
 and Anginas. The organs and cavities of the face are easily invaded 
 by pathogenic germs. Hence the usefulness, even under normal 
 conditions, of practising antisepsis of these parts in a certain measure. 
 Greater care is naturally given to the buccal cavity. 
 
 Even in health it is indispensable to cleanse the mouth and the 
 teeth frequently. It is well, for instance, to cleanse the teeth in the 
 
THERAPEUTICS OF INFECTIOUS DISEASES. >;<;.; 
 
 morning, in the evening, and after each meal. Bm he are gero rally 
 employed for this purpose, which have the great inconvenience of 
 retaining organic particles liable to a rapid putrefaction. Tlii i 
 remedied by washing the brush with some anti eptic solution. A 
 good one is thymic acid in the strength of L:3000. In the <■• 
 of infectious diseases the care of the mouth requires special attention. 
 The dryness of the mucous membrane diminishe it- mean* of pro- 
 tection and favors the multiplication of germs which tend to invade 
 the deeper parls and pcnd rate i hrough the excretory ducts, notably 
 the parotid gland. 1 1 will, therefore, be well to prescribe frequent 
 lavage with an alkaline water, viz., with bicarbonate or borate solu- 
 tions. Antisepsis is not realized thereby, bul the mucous membrane 
 is thus indirectly placed under better conditions of resistance. I er- 
 mentation of carbohydrates found in the mouth produce acids which 
 harm the epithelium. By neutralizing these acids the alkalies act 
 in aphtha. While it is true that the fungus producing this stomatitis 
 lives preferably in alkaline media, the observation by Gubler that it 
 develops in the mouth when the medium becomes arid and ci 
 to multiply when the latter is rendered alkaline, is simply due to the 
 fact that acids diminish the vitality of the mucous membrane, and 
 not, as has long been asserted, because they favor the vegetation of 
 the fungus. 
 
 When infection is more profound, profuse lavage of the mouth is 
 generally practised. The patient sits up, inclines the head forward 
 while the antiseptic fluid is thrown into the mouth. A good many 
 mixtures have been proposed. In our wards we employ in stomatites 
 and anginas a solution containing 10 per 1000 of carbolic acid and 
 1 per 1000 of thymol. Solutions of chloral hydrate. 1: 100. are also 
 very good. When microbic lesions are already developed applica- 
 tions of antiseptic or caustic substances should be made. In stoma- 
 tites, whatever their nature may be, cauterizations by alum, nitrate 
 of silver, and especially salicylic acid, are practised, the latter being 
 used in the proportion of 1 : 10 dissolved in a mixture of equal parts 
 of alcohol and glycerin. Phenol, or sulphorieinated 1 salol or tincture 
 of iodine are also useful. We have often obtained satisfactory results 
 from the employment of tincture of cochlearia. 
 
 There is a special form of gingivitis — expulsive gingivitis— which 
 
 1 There is a French preparation, "acide sulforicinique," composed of oleum ricini and 
 sulphuric acid. Antiseptic substances, such as salol and phenol, may be combined 
 with this acid to form sulphorieinated salol. or phenol, etc. — Translator. 
 
664 INFECTIOUS DISEASES. 
 
 is very grave because it causes shedding of the healthy teeth. It 
 should be treated by strong antiseptics, such as carbolic, salicylic, 
 or chromic acid. Finally, such antiseptics as creosote, methyl sali- 
 cylate, and arsenious acid are employed for the treatment of dental 
 caries. 
 
 In most cases of anginas antiseptic lavage is sufficient. In per- 
 sistent lesions, however, painting with more energetic antiseptics is 
 indicated. Tincture of iodine, salol, hydroglycerinated solutions of 
 corrosive sublimate, and camphorated naphthol are the substances 
 most frequently employed. It is well, however, not to prolong their 
 use, since they produce irritation and maintain the lesion against 
 which they are directed. The therapeutic indications are the same 
 in suppurating tonsillites. Gargles or, still better, slightly antiseptic 
 lavage, is also prescribed. In some cases puncture of the abscess is 
 at a certain moment to be practised. An emetic is sometimes admin- 
 istered for this purpose, but this medication acts only when the lesion 
 is at the point of opening spontaneously. It is then useless and, what 
 constitutes a graver objection, it has the inconvenience of depressing 
 the patient. 
 
 Unlike the buccal cavity, the nasal cavity does not need antiseptic 
 lavage in health. In the course of infectious diseases it is well to 
 introduce a slightly volatile antiseptic substance. Mentholated olive 
 oil in the proportion of 1 : 40 fulfils this indication ; every morning 
 five or six drops of it are introduced into the nostrils. A salve con- 
 taining twenty grams of vaseline, one gram of resorcin, and half a 
 gram of menthol is also employed. When the nasal fossa? are more 
 particularly affected, whether the lesion be primary or secondary, 
 antisepsis is likewise indicated. 
 
 Simple corj^za is often cured when slightly antiseptic powders are 
 employed from the beginning. Many formulas have been given. The 
 author generally employs a mixture made with equal parts of pul- 
 verized boric acid, benzoin powder, and salicylate of bismuth. Ten 
 grams of each of these substances are prescribed, and a half gram 
 of hydrochlorate of cocaine is added. 
 
 Serious rhinites are sometimes observed in the course of certain 
 infections. The purulent rhinitis of scarlatina represents a very 
 important cause of death. Its treatment must be energetic. We 
 have recourse to lavage with peroxide of hydrogen. In order, how- 
 ever, to insure cleansing of the nasal fossse, flow of the discharge from 
 within outward must be secured. Inflammation of the nasal fossae 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 666 
 
 may spread it to the sinuses of the face. This complication i 
 readily be recognized by the following two symptoms: n purulent 
 discharge from one nostril and a facial neuralgia. The treatment 
 consists in causing the patient to inhale through the di eased nostril 
 by means of a funnel turned upside down upon a bowl of hoi water 
 intowliic.h has been poured a teaspoonful of a 4 per cent, alcoholic 
 solution of menthol. The inhalations are repented hourly; each 
 sitting should Last five minutes. II' the inflammation involves the 
 Eustachian tube and the middle ear this new complication Bhould be 
 combated by paracentesis of I lie tympanum and irrigation. In our 
 wards we employ lavage with bonded water, which is followed by 
 the introduction of a few drops of carbolized glycerin. We have 
 recently obtained highly satisfactory results from lavage with a 
 1:500 solution of methylene blue. 
 
 Finally, in order to conclude what we have to say about antisep- 
 sis of the face, we shall recall what care is to be given to the ocular 
 apparatus. Conjunct ivites are frequent in infections; they are, 
 however, generally benign. They heal under use of simple washings 
 with hot borated water, followed by an occlusive dressing. In case 
 of severe pain, a drop of a collyrium made with neutral sulphate 
 of atropine is instilled into the eye. 
 
 Three infections frequently give rise to grave lesions of the eyes. 
 These are zona, variola, and gonorrhea. In the case of zona, atropine 
 and absolute occlusion of the eye are prescribed. Variola often pro- 
 duces purulent conjunctivites, the principal danger of which is con- 
 secutive keratitis. For conjunctivitis we employ lavage with 1 : 8000 
 solution of potassium permanganate, 5:1000 solution of protargol, 
 or 1:500 solution of methylene blue. Should keratitis supervene, 
 methylene blue alone is applicable. At the same time atropine is 
 utilized to some extent. 
 
 The treatment of purulent gonorrheal conjunctivitis consists in 
 applications of silver nitrate or protargol. 
 
 Antisepsis of the Respiratory Passages. Antisepsis of the re- 
 spiratory passages may be realized: (1) by inhalations of volatile 
 substances; (2) by directly introducing liquids or powders into the 
 upper parts or, in the case of the lungs, by injecting them directly 
 into their parenchyma; (3) by turning to profit elimination through 
 the alveoli of certain volatile principles which may be introduced 
 into the organism by any channel. 
 
 Inhalations of volatile substances are daily employed in the treat- 
 
(366 ISFECTIOUS DISEASES. 
 
 ment of laryngeal, tracheal, or bronchial infections. Menthol is 
 commonly used. A 4 per cent, alcoholic solution is made use of. A 
 dessertspoonful of this is put in a bowl of hot water and the latter 
 covered with an inverted funnel, and inspiration made through the 
 tubal part of the funnel. Another method consists in causing the 
 patient to breathe an atmosphere charged with medicated vapors. 
 Tar is often employed for this purpose. Dr. Tapret has proposed to 
 have patients, particularly tubercular subjects, sojourn in rooms in 
 which a 10 per 1000 creosote solution is sprayed. We may also men- 
 tion sulphurous waters, which are employed in chronic infections. 
 In other instances water charged with antiseptic substances is 
 sprayed in front of the mouth of the sufferer. Naphtholated water 
 (naphthol 0.25, alcohol 25 grams, water 75 grams), Van Swie ten's 
 solution, 1 : 1000 solution of biniodicle of mercury, carbolized water, 
 and water charged with oil of turpentine or creosote have also been 
 utilized. 
 
 The respiratory tract being largely open to the exterior, medicines 
 may easily be introduced therein. This is currently done as regards 
 the larynx. Antisepsis is thus realized just as in the case of a surface 
 exposed to the air. As regards the more deeply seated parts, we 
 have to be contented with injecting a few drops through the larynx 
 or, in the case of tracheotomy, through the tracheal wound. Men- 
 tholated oil in the proportion of 1 : 40 is generally employed. 
 Should it be thought advantageous, injections by means of a needle 
 introduced through the skin into the trachea may readily be prac- 
 tised. 
 
 In the presence of a well-circumscribed pulmonary focus one is 
 always tempted to inject some antiseptic directly into it. Numerous 
 experiments have been made in this direction, notably by Dr. Lepine 
 and Dr. True. It is necessary not to exceed 1 c.cm. or 2 c.cm. beyond 
 the surface of the lung, in order to avoid entering an important 
 vessel. By injecting the fluid slowly it is possible to introduce a 
 considerable amount of it. Lepine injected as much as 100 c.cm. 
 through five different punctures. Benzoate of soda and potassium 
 iodide have been introduced in this manner. Lepine utilized bin- 
 iodide of mercury in a dose of 1 : 40,000. These attempts have been 
 made particularly in pneumonia. It would be interesting, however, to 
 renew these attempts in cases of circumscribed pulmonary gangrene. 
 
 The majority of volatile substances that are eliminated through 
 the respiratory apparatus may exercise a medicinal action while 
 
THERAPEUTICS OF INFECTIOUS DI8EA8ES. 667 
 
 being eliminated, no matter through which channel they are intro- 
 duced. According i,o this principle, if i rational to cause patienfa 
 to ingest preparations of turpentine or eucalypti! . potion containing 
 from four to six grams of hyposulphite of soda, or to administer for 
 the same purpose sulphurous waters. According to the same idea, 
 the use of gaseous enema I a, of carbonic add, and sulphuretted hydro- 
 gen has been advised. Too much reliance, however, should nol be 
 placed upon this method, since we have recognized, with Dr. Gamier, 
 that sulphuretted hydrogen, even when introduced in large amounts, 
 is not found in flie exhaled air. At least il ii impo ible to detect 
 the slightest trace of it by placing before the mouth of the patienl 
 a paper preparation of acetate of lead. 
 
 For the treatment of respiratory affections the subcutaneous 
 method may likewse be utilized. Eucalyptol is often injected in 
 this manner. Creosote is also administered either per os, or by sub- 
 cutaneous injections, or through enemata. In the first case, pills of 
 10 centigrams are generally employed, of which three to five are 
 taken with the two principal meals. In the second case, oily solu- 
 tions in the proportion of 1 : 15 are used. Burlureaux advia 
 inject them slowly at the rate of forty drops per minute, which means 
 20 grams in an hour. As much as 100 grams and even 150 
 grams of the fluid have been introduced in this manner. In general 
 it is convenient to prescribe an enema containing from 4- gram to 
 1 gram of creosote incorporated in an oily emulsion. The skin may 
 often be painted with creosote or guaiacol. Such applications are 
 well borne when they are not too strong. They have the strange 
 property of lowering the temperature and producing alarming mani- 
 festations if the dose of creosote is too large. The author prescribes 
 friction with a 10 per cent, guaiacolated salve the size of a hazel- 
 nut. In fact, the recent tendency is to substitute for creosote some 
 well-defined chemical product, such as guaiacol, or less irritating 
 substances, such as carbonate of creosote or of guaiacol. Creosote and 
 its derivatives render service in the treatment of all torpid infections 
 of the respiratory passages, particularly in cases of tuberculosis. 
 They are not without some disadvantages. Creosote sometimes pro- 
 duces digestive disturbances which are avoided by administering it 
 in the form of enemas. Some authorities believe that it produces 
 congestion and hemoptysis. Therefore, its administration is to be 
 avoided in those cases of tuberculosis in which there is tendency to 
 pulmonary hemorrhages. Contrary to what has been stated by some. 
 
6S8 INFECTIOUS DISEASES. 
 
 creosote is often useful in acute forms, and it is still the best medicine 
 for the treatment of chronic pulmonary tuberculosis. 
 
 Antisepsis of the Alimentary Canal. The intensity of putrefac- 
 tions that occur even normally in the digestive canal, the frequency 
 and gravity of disturbances resulting therefrom, the role of gastro- 
 intestinal putrefactions in the development of infectious or non- 
 infectious secondary lesions, having, apparently, nothing to do with 
 digestive disorders, explain why therapeutists have multiplied their 
 efforts to combat the microbes which swarm in this part of the 
 organism. Three principal methods are now at our disposal. We 
 may restrain fermentations by suppressing fermentable aliments. 
 We may expel the infected remains of digestion and at the same 
 time sweep off microbes and their toxins. Finally, we may prescribe 
 antiseptic substances. 
 
 The digestive canal may be rendered antiseptic by means of diet. 
 For the adult, milk diet is generally prescribed, the influence of 
 which in this regard was clearly demonstrated by the investigations 
 of Gilbert. In mild cases it suffices to modify the diet and restrict 
 readily putrescible foods like meat. On the other hand, rice, vege- 
 tables, and cooked foods are prescribed. In a grave case, even milk 
 is too fermentable. All alimentation is to be suppressed and the 
 patient placed on water diet. This is particularly indicated in the 
 case of the newborn suffering from gastrointestinal disturbances 
 which at times rapidly prove fatal. Boiled water to which is added 
 a small amount of sugar and 10:1000 of lactic acid is given. As 
 ill-digested aliments are easily attacked by microbes, gastrointestinal 
 antisepsis can likewise be effected, although in an indirect manner, 
 by modifications of alimentary hygiene. It is probable that the 
 ingestion of hydrochloric acid acts in this manner. This acid was 
 considered as an antiseptic secreted by the mucous membrane of the 
 stomach. The intense fermentations of hyperchlorhydria are due to 
 the fact that the food is not well digested. Alkalies will then diminish 
 putrefactions and, reciprocally, hydrochloric acid will play the same 
 role in cases of hypochlorhydria. 
 
 Microbes may be mechanically thrown out. Profuse lavage of the 
 stomach or intestine possesses the treble advantage of freeing the 
 digestive canal of fermentable substances, microbes, and toxic prod- 
 ucts resulting from their multiplication. The same indication is 
 fulfilled by the use of emetics and purgatives. The secretions and 
 fluxes provoked by them bring about a similar cleansing. Among 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 869 
 
 purgatives calomel seems to be, in thi respect, the most efficient, 
 for Lt exerts at the same time an antiseptic action. 
 
 (j!;i,si,r()iiii,<\s!Jii:il antiseptics, properly so called, may be divided 
 from a practical standpoint into two groups: soluble and insoluble 
 antiseptics. The soluble ones most frequently employed are sulpho- 
 earbonafed wafer, diloroform water, and solutions of lactic and car- 
 bolic acid. It has been noted, however, thai these substanct 
 they advance in the alimentary canal are absorbed and booh disap- 
 pear. Therefore, their germicidal influence n exerted upon a 
 limited extent of flic digestive tract. Hence, it hae been recom- 
 mended to prescribe insoluble antiseptics, pari of which may be 
 modified and penetrate flic organism, while another part pi 
 through the whole length of the canal withoul any alteration. 
 
 Naphtholin was first praised. It has, however, been abandoned, 
 for it often produces dysuria and pruritus, and may be dangerous to 
 the sight, judging from the cataract which is caused by its ingestion 
 in rabbits. In consequence of Prof. Bouchard's experiments, ,i- 
 naphthol was utilized, instead of which, according toDr.Maximowieh, 
 a-naphthol may be used, which has the double advantage of being 
 more antiseptic and less toxic. The burning taste of naphthol makes 
 it necessary to administer it in wafers. It may be given alone or 
 associated with laxative or antidiarrheal substances. The dose is 
 from one to three grams in twenty-four hours. It is well, however, 
 to administer it in fractional doses, since the successive use of small 
 doses produces a more marked antiseptic action than the same 
 amount ingested at once, and is less irritating for the stomach. In 
 order to avoid the inconveniences due to the caustic property of 
 naphthol, two of the derivatives of this medicine, betol and benzo- 
 naphthol, are at present frequently made use of. Their antiseptic 
 power is not as great, but they are well borne even by delicate 
 stomachs, while naphthol itself has the inconvenience of causing pain 
 and gastric burning in certain individuals. Benzonaphthol, which is 
 the one commonly employed, is prescribed in daily doses of from two 
 to four grams. It is tasteless and, therefore, can be given to children 
 and such patients whose prostrated condition prevents them from 
 swallowing wafers. It may be administered in wafers, powders, in 
 which case it is taken in some liquid, and finally, in the form of a 
 potion. 
 
 Iodoform, which has sometimes been employed as an intestinal 
 antiseptic, is hardly ever used now for this purpose. Salol, in doses 
 
6 70 IXFECTIO US DISEA SES. 
 
 of from 2 to 4 grams, acts particularly upon the stomach; in 
 fact, it is decomposed in the duodenum into carbolic and salicylic 
 acids, which are soon absorbed. This medicine is especially useful 
 when there is reason to believe that infection has invaded the biliary 
 passages, salicylic acid passing into the bile, where its aseptic action 
 is exerted. 
 
 Subnitrate or salicylate of bismuth is often combined with the 
 antiseptics above indicated. Salicylate of bismuth is decomposed in 
 the presence of sulphuretted hydrogen originating from intestinal 
 putrefaction; insoluble bismuth sulphide is produced, and the salicylic 
 acid thus liberated is found in the urine, in which it may be detected 
 by means of perchloride of iron. Some authors believe that this 
 offers a very simple means of determining the intensity of digestive 
 putrefactions. Instead of administering through the mouth, anti- 
 septics may be introduced by the rectum. Various medicinal enemas 
 have been favored. Those with carbolic acid were once quite fre- 
 quently employed. 
 
 Although enemas are of service, they have the inconvenience of 
 affecting only the terminal part of the large intestine. On the other 
 hand, the fluid arriving under a certain pressure distends the rectal 
 enlargement, and thus aggravates or maintains certain disorders. 
 Irrigation by means of a soft sound introduced into the colon is free 
 from this disadvantage. Very slight pressure may be employed, so 
 that the liquid flows slowly and, being introduced deeply into the 
 canal, cleansing is more complete. Another advantage of this method 
 is that a large amount of fluid may be circulated. Mild solutions of 
 potassium permanganate are often used (1 : 10,000) and give very 
 satisfactory results in the treatment of dysentery and dysenteriform 
 ententes. Cantani employed in cholera a fluid containing from 3 to 
 6 grams of tannin, 30 to 50 grams of gum arabic, and 30 to 50 drops 
 of laudanum per litre (quart). Of course, the formulas may be 
 varied ad infinitum. We shall first notice the advantages obtained 
 from intestinal lavage with subnitrate of bismuth. This substance, 
 being deposited upon the mucous membrane, forms a protective layer, 
 and may keep the antiseptic incorporated in contact with the diseased 
 parts. In order to introduce bismuth, which is given in doses of from 
 10 to 20 grams, it is suspended in quince mucilage or gum arabic 
 water. 
 
 In cases of infection of the large intestine we have obtained remark- 
 able results from the use of lavage with peroxide of hydrogen. We 
 
THERAPEUTICS OF INFECTIOUS DI8EA8E8. 07] 
 
 introduce from . r )0 c.cm. to LOO c.cm. of peroxide of hydrogen, which 
 is rendered alkaline just before use by the addition of a double volume 
 of Vichy water. Peroxide of hydrogen may al o be poured into a 
 litre (quart) of boiling water in which should be dissolved 5 grams 
 of sodium chloride, :; grams of sodium pho phate, and \ gram of 
 sodium bicarbonate. Peroxide of hydrogen acta a an antiseptic. 
 'The oxygen which is Liberated hinders the development of the numer- 
 ous anaerobic microbes inhabiting the intestine and al the same 
 time exercises ;i very f;ivor;il)le stimulation upon the walk of the 
 digestive canal. This medication is particularly useful in the treat- 
 ment of oolites ;i,ik| notably dyscuteriform COlite , 
 
 Digestive antisepsis is evidently indicated in gastrointestinal in- 
 fections. An attack of indigestion, seasonal diarrheas, alimentary 
 poisonings, as well as typhoid fever, cholera, and dysentery, are well 
 treated by this medication. In typhoid fever the administration of 
 naphthol or benzonaphthol lias the advantage of diminish ing toxic 
 manifestations by checking putrefactions. The tongue remains 
 moist, delirium is rare, tympanites less marked, and the i'ccul matters 
 are almost odorless. As gastrointestinal putrefactions play a con- 
 siderable role in a number of infectious diseases, the use of am i>ej >t ics 
 is frequently indicated. In affections of the liver and kidneys, the 
 transformation and elimination of the intestinal poisons being imper- 
 fectly effected, it is important to diminish this principal source of 
 intoxication. The same is true of certain cutaneous infections. 
 Prof. Bouchard long ago laid stress upon the excellent efTec* - 
 intestinal antisepsis in combating acne and furunculosis. Beer yeast 
 probably acts in an analogous manner by regulating the digestive 
 functions. 
 
 Antisepsis of the Serous Membranes. Antiseptics, once fre- 
 quently employed against infections of serous membranes, are no 
 longer used, except in accordance with certain indications. The 
 physician is guided bj 7- the course or the bacteriological nature of the 
 effusion. Thus, in pleurisies with the pneumococcus, one or several 
 thoracenteses often suffices. In streptococcic or in pneumococcic 
 pleurisies, which are reproduced repeatedly or are developed within 
 a partition of the pleura, operation for empyema with or without 
 costal resection is resorted to. After the focus is opened it is well 
 to irrigate with a mild antiseptic solution, for example, a 1 : 1000 
 solution of corrosive sublimate. The cavity is Then washed out with 
 boiled water in order to carry away the antiseptic. In the majority 
 
672 INFECTIO US DISEASES. 
 
 of cases a single lavage suffices. If, however, the fluid is rapidly 
 reproduced, or it becomes fetid, or the patient presents symptoms 
 due to purulent absorption, antiseptic lavage should again be resorted 
 to. For the same reason these irrigations should always be employed 
 in cases of putrid pleurisies. If the effects of corrosive sublimate are 
 feared a 4 per cent, solution of creolin, a 1 per cent, solution of 
 chloride of zinc, or 1 or 2 per cent, solution of salicylic acid may 
 be used. Not infrequently, however, the practitioner substituting 
 asepsis for antisepsis is contented with lavage with boiled water. 
 
 In cases of purulent tubercular pleurisy surgical intervention does 
 not yield very successful results. It has, therefore, been suggested 
 to inject antiseptic solutions into the pleura. Camphorated naphthol 
 particularly has been used in this case. 
 
 Interstitial Antisepsis. Interstitial antisepsis may be practised 
 by introducing germicidal fluids into the diseased tissues. The 
 remarkable results obtained by this method in the treatment of 
 malignant pustule are well known. Davaine and Cezard were the 
 first to treat anthrax infection by means of interstitial injections of 
 iodine. They began with 1: 4000 solutions and gradually increased 
 to 1 : 400 dilutions. Far more concentrated solutions may easily 
 be employed. The author recommends a mixture of one part of 
 tincture of iodine with one or two parts of iodided water. Fifteen 
 to 20 drops of this liquid are injected into the swollen parts every 
 morning and evening by three or four punctures made around and 
 outside the vesicular zone. The needle is obliquely introduced be- 
 neath the skin and the fluid is injected very slowly. The author also 
 makes subcutaneous injections around the congested glands. The 
 treatment is thus continued every day by regulating the amount of 
 the fluid to be introduced according to the general state of the patient 
 and the aspect of the local lesion. The injections should not be 
 suspended until amelioration is well marked, edema is diminished, 
 the skin recovers its suppleness, and fever has disappeared. During 
 and after employment of iodine injections it is well to keep the 
 pustule covered with an antiseptic dressing, such as Van Swieten's 
 solution, mercurial ointment (Cucco), camphorated naphthol, etc. 
 When the eschar separates the part is covered with iodoform. Thus 
 the too rapid development of pyogenic agents and other accidents 
 may be avoided. 
 
 Subcutaneous injections of tincture of iodine are well borne, 
 although they are somewhat painful. Some transitory phenomena of 
 
THERAPEUTICS OF INFECTIOUS DI8EA8E8. i;7 .; 
 
 iodism may at times occur under their influence. In om 
 observed at the point of several punctures little painful indurations 
 which finally healed at the end of a few weeks without any accident. 
 Russian surgeons have employed for the same purpo e a olution of 
 corrosive sublimate. Good results have also been obtained with \\ 
 per cent, .solutions of carbolic acid. This fluid is well borne and 
 gives rise lo no disturbance. 
 
 II, has been suggested to treal erysipelas in the same manner and, 
 in order to arrest its spread, in inject antiseptic fluids a1 the margin 
 of the inflamed part. In the case of facial erysipelas, however, the 
 evolution seems to us too favorable to necessitate so delicate a 
 method. In erysipelas of the limbs, and especially of the l< 
 extremities, with tendency to diffuse suppuration and sphacelus, the 
 author has several times injected peroxide of hydrogen. He has 
 always utilized the commercial solution diluted with an equal volume 
 of a 4 : 1000 sodium bicarbonate solution. The fluid thus obtained 
 is injected beneath the skin through several punctures in such a 
 manner as to surround the lesion. From 5 to 10 c.cm. of the fluid 
 is thus introduced morning and evening. These injection- produce 
 truly marvellous effects, and in several cases they have speedily 
 arrested the invading course of a suppurated or gangrenous Lesion. 
 
 When a part is attacked by sphacelation and seems irretrievably 
 lost, an attempt may be made to transform it into a harmless mass 
 by a sort of embalmment. This is what Prof. Bouchard realized in a 
 case of gangrene of the lower extremity due to post-typhoidal arter- 
 itis. He prescribed injections of a 25 per cent, creosote solution into 
 the diseased limb. The putrefaction was rapidly arrested: the gan- 
 grenous member became mummified, and was subsequently elimin- 
 ated by spontaneous amputation. 
 
 General Antisepsis. A last question remains: Is general, at least 
 relative, antisepsis possible? Is it possible to diminish, if not to 
 abolish, the aptitude of the fluids and tissues to microbic invasions ? 
 
 It is certain that we here encounter great difficulties and that 
 antiseptic substances are too toxic to be administered in amounts 
 responding to this end. In two instances the experiment was made 
 involuntarily : It occurred at the time when carbolized enemas were 
 administered in the treatment of typhoid fever. Inadvertently the 
 mother solution was injected into two patients. Fearful manifesta- 
 tions immediately occurred, but profuse intestinal irrigation prac- 
 tised forthwith succeeded in carrying out the poison. The curious 
 
 43 
 
674 INFECTIOUS DISEASES. 
 
 fact, however, is that the fever fell and did not rise again. The 
 disease was checked, but the fatal dose had nearly been reached. 
 
 There is, however, an inoffensive substance which, according 
 to some scientists, renders the organism aseptic. This substance 
 is tannin. The simple injection of this medicine, it is said, suf- 
 fices to render the blood unfavorable for the development of mi- 
 crobes. It is evidently interesting to resume the study of these 
 phenomena. 
 
 While it is hardly possible to realize general antisepsis of the 
 organism against the majority of microbes, we are able, by the use 
 of specifics, to prevent the development of certain determined 
 agents. The medicines described under this name, at least some of 
 them, hinder the multiplication of a given microbe. These are selec- 
 tive antiseptics. At least this has been demonstrated for the salts 
 of quinine in paludism. The germicidal serums act in the same 
 manner, and the facts already known lead us to the hope that we 
 shall see an increase in the list of substances to which certain microbes 
 are so sensitive that minute amounts, in nowise dangerous for the 
 organism, suffice to arrest their development. 
 
 Conclusion. If we consider the present tendency of surgeons we 
 find that, after having used and at times abused antiseptics, there 
 is a growing inclination to more and more restrict their employ- 
 ment. 
 
 Strong antiseptics are rejected and reserved for certain exceptional 
 cases. On the other hand, asepsis is often substituted for antisepsis 
 by the use of lavage with boiled water. When antiseptics are em- 
 ployed, all those which may produce a caustic action should be 
 eliminated, and it should be borne in mind that germs seem to become 
 rapidly habituated to their germicidal action. It is, therefore, neces- 
 sary to frequently change the substances employed. Moreover, it is 
 well to remember that an antiseptic often acts as much by stimu- 
 lating the tissues as by destroying the microbes. The latter are well 
 protected within the organism. They seldom vegetate upon the sur- 
 face. They penetrate into the folds of the tissues and especially into 
 the glandular crypts, vegetate behind masses of cells, and are thus 
 protected against antiseptics. We must not, therefore, depend too 
 much upon this method, which once seemed so rich in promises, nor 
 must we forget that the best antiseptics are those which are secreted 
 by the organism itself. The efforts of the physician should, therefore, 
 be directed to stimulate the reactions of the system. 
 
THERAPEUTICS OF INFE0TI0U8 DI8EA8E8. 
 
 Antitoxinic Method. 
 
 The antiseptic method intended to destroy germ i related to the 
 antitoxinic method which destroys or neutralize) the poi on . We 
 have already shown thai the true antitoxin are those which are 
 secreted by the animal organism in the cour e or in consequence of 
 infections. There are, however, pharmaceutical ubstance* capable 
 of neutralizing certain microbic poisons. We -hull divide them into 
 
 three groups .'recording as they absorb poisons, precipitate them, or 
 
 form with them combinations rendering them inoffensive. 
 
 The absorption of microbic toxins may be accomplished by mi 
 of charcoal powder. This powder fixes noi only coloring and odorous 
 substances, but it possesses the power of retaining alkaloids. It was 
 supposed, therefore, especially at the epoch when microbic poisons 
 were believed to be analogous to alkaloids, that the ingestion of char- 
 coal powder would diminish intestinal putrefaction. This is what has 
 in fact taken place. This medication, however, must be supple- 
 mented by prescribing a purgative every five or six days, in order 
 to cleanse the intestine of the accumulated charcoal, which is full of 
 toxins. 
 
 Albumins and alkaloids are precipitated by certain substances 
 which act upon these two groups of bodies. Such a substance is 
 tannin. It may, therefore, be hoped that this medicine will prove 
 useful in the treatment of microbic intoxications by rendering harm- 
 ful substances insoluble. In fact, the employment of tannin, tanni- 
 gen, or tannalbin gives very good results in certain digestive infec- 
 tions. In the course of putrefactions, certain chemically well-defined 
 substances are produced, which may easily be neutralized. Thus, 
 sulphuretted hydrogen, which is so often originated in the intestine, 
 is transformed into an insoluble sulphide by the salts of bismuth. 
 The latter medicine acts not only mechanically, but also as an anti- 
 toxic. 
 
 It may also be asked whether poisons cannot be neutralized by 
 certain insoluble precipitates which absorb toxins. Evidently the 
 poison is not thus destroyed, and experimentation demonstrates that 
 the combination is not very intimate, since the precipitate acquires 
 noxious properties. Nevertheless, possibly some part of it is neu- 
 tralized in this manner, which would be a favorable result. 
 
 When toxins combine with certain bodies they become less toxic. 
 This is notably what occurs when the}" come in contact with iodine 
 
676 INFECTIOUS DISEASES. 
 
 and its derivatives. The action of iodine and trichloride of iodine 
 has been well demonstrated by numerous experiments bearing espe- 
 cially upon tetanic and diphtheritic toxins. Probably iodoform acts 
 in the same manner. The latter substance, which is not a strong 
 antiseptic, gives excellent results in the treatment of wounds, because 
 it is decomposed and liberates iodine which, on being generated, 
 unites with toxins and suppresses their action. Carbolic acid seems 
 to act similarly by neutralizing the tetanic toxin. Bacelli has advised 
 the injection of a 2 or 3 per cent, solution of carbolic acid beneath 
 the skin of tetanus patients during twenty days or more. Each 
 injection is to be 3 eg. to 4 eg. Thirty centigrams of carbolic acid 
 is daily introduced in addition to 4 eg. to 6 eg. of morphine. This 
 method counts at present a certain number of successes. 
 
 Lastly, if we remember that toxins are destroyed by oxidation, we 
 readily understand the advantages to be derived from oxidizing sub- 
 stances like benzoate of soda. Their administration acts both upon 
 the poisons of the microbes and upon those, by no means less im- 
 portant, which are originated within the organism. These few ex- 
 amples show how interesting it would be to pursue investigations 
 concerning means of neutralizing toxins within the organism. 
 
 This antitoxic method, which as yet includes few medicinal sub- 
 stances, assumed great importance after the discoveries of Behring 
 and Kitasato. The majority of medicinal serums are included in this 
 group. 
 
 Specific Medication. 
 
 Given a disease to find a remedy to cure it is a problem laid down 
 by the ancients. The search for specifics, the preoccupation of which 
 is constantly present in the writings of Pliny, persisted until a recent 
 epoch. The search for specifics, which was nearly abandoned at the 
 time experimentation made us better acquainted with the mode of 
 action of medicines, assumed fresh importance with the discoveries 
 of serumtherapy. The medicinal serum is the specific remedy par 
 excellence. It may be said to be the antidote of the microbic poison. 
 The antidiphtheritic serum, for instance, is the specific medicine of 
 the disease. Its injection causes the pseudomembranes to exfoliate 
 and arrests the symptoms of intoxication. The fact that it has no 
 influence upon identical or analogous pseudomembranes created by 
 other pathogenic agents well demonstrates its specific action. The 
 employment of the serum is not only the best treatment, but also 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 677 
 
 represents a means of diagnosis. It confirms the old adage '.NcUuram 
 morborum curationes ostendunt. 
 
 In the case oi 8 therapeutic serum the medicinal lib tance repre- 
 sents a product of reaction againsl a determined toxin. It is, there- 
 fore, intelligible thai the antitoxin should be special and elective. 
 [t is, however, interesting to find in nature vegetable or mineral 
 substances which possess an analogous property and are bo decidedly 
 specific that they iimy equally serve diagnosis and treatment. The 
 specific action is, however, less clear. Although each of these sub- 
 stances cures one disease, they are capable of improving 
 others, or at least combating certain symptoms. 
 
 Aside from therapeutic serums, we are aj presenl acquainted with 
 four specific substances: cinchona, mercury, iodine, and salicylic 
 acid. 
 
 Cinchona and Quinine. The febrifuge action of cinchona bark 
 seems to have been observed long ago by the inhabitants of Peru. 
 It was not, however, known in Europe until after the middle of the 
 eighteenth century. The remedy was introduced by the Com 
 El Cinchon, Vice-queen of Peru, and almost coincidently by the 
 Jesuit missionaries. It was at first known under the designation 
 "Countess' powder" and "Jesuits' powder." In 1679, Louis XIV. 
 bought from the Englishman, Talbot, the secret of a febrifuge remedy 
 which was nothing else than a wine prepared with cinchona bark. 
 It was not until the next century, in 1737, that La Condamine and 
 Joseph of Jussieu determined the cinchona tree. Finally, in 1820, 
 Pelletier and Caventou succeeded in extracting the principal alkaloid 
 of cinchona — quinine. 
 
 Cinchona or quinine is not a common antipyretic medicine. It is 
 first of all a specific antipyretic acting upon malarial fevers. The 
 employment of the medicine was regulated by Torti and Sydenham. 
 The method of Torti, which consisted in administering the drug 
 before the paroxysm, was abandoned by its author, who adopted 
 Sydenham's or the English method, the essential principle of which 
 was to give cinchona at the end of the paroxysm. It is known that 
 quinine was abandoned under the influence of Broussais* ideas or 
 was given in insufficient doses, and the fearful reign of malarial fever 
 in the troops of Algeria is not forgotten. At the present day quinine 
 is generally prescribed in one-half to one gram doses. Two or three 
 grams is but exceptionally reached. It should be administered either 
 after the paroxysm or five or six hours before its return. The latter 
 
678 ISFECTIOUS DISEASES. 
 
 method is the more usual one. Laveran advises its administration 
 for three days in doses of one-half to one gram (hydrochlorate of 
 quinine), then in doses of 60 eg. to SO eg. on the eighth, ninth, and 
 tenth days, and a renewal of the same prescription on the fifteenth, 
 sixteenth, twenty-first, and twenty-second days. 
 
 Since the researches of Binz it is known that quinine salts exert 
 a harmful action upon ameba?. They are powerless against plants 
 of a low organization, while they rapidly destroy protozoa. By 
 mixing a drop of blood containing hematozoa with a drop of a weak 
 quinine solution we may see how rapidty the movements of the 
 pigmentary grains and the motile filaments are arrested. The fever 
 may recur, because quinine, which kills the adult hematozoa, acts 
 with much less energy upon the encysted germs of these parasites. 
 Thus, quinine represents a specific medicine belonging to the group 
 of germicidal drugs. It is a parasiticide. This is a very important 
 fact, but it would not be safe to generalize the conclusion. It seems 
 probable, however, that such is also the case with mercury — that 
 this substance acts in syphilis as a parasiticide. 
 
 Mercury and Iodine. It was not by chance, as has been asserted 
 by Fallope, that mercury was first employed. It had long been 
 praised by the Arabs in the treatment of leprosy. It was in use 
 against parasites, pedicular affections, and the itches. It was 
 tried in sj^philis by analogy. Employed for the first time by Wich- 
 mann in 1497, it was particularly praised by Berenger (of Carpi) and 
 Jean de Vigo, who prescribed it in the form of plasters; by Fracaster, 
 who employed it in friction, and by Matthioli, who administered it 
 internally. At present mercury is administered by the digestive canal 
 or by inunctions, by subcutaneous or intramuscular injection, and, 
 in grave cases, by intravenous injection. We may employ metallic 
 mercury (blue pill, Sedillot's pills, inunctions with Neapolitan ungu- 
 entum, injections of mercury, etc.), the insoluble salts (pill of proto- 
 iodide, injections of calomel), the soluble salts, notably corrosive 
 sublimate (Dupuytren's pills, Van Swieten's solution), biniodide 
 (biniodizeel oils), peptonate, benzoate, and cyanide. The soluble 
 salts are, of course, used for intravenous injection. Sometimes cor- 
 rosive sublimate is employed in doses of 1 mg. to 8 mg.; oftener 
 cyanide of mercury. 
 
 The powerful antiseptic properties of mercury salts lead to the 
 presumption that this medicine acts upon the pathogenic agents of 
 syphilis. Direct experimentation being impracticable, hypotheses 
 
THEMAPEUTICS OF INFECTIOUS DISEASES. 670 
 
 have been advanced, It is well to notice, however, thai the question 
 is undoubtedly one of specific action, for mercury doe nol acl imi- 
 larly against other infections. On the other hand, il i nol equally 
 useful against all syphilitic tnanife tation . [n the prima] 
 i Mercury acts upon the chancre and adenites. tts action is still more 
 marked upon the secondary manifestations. General treatment 
 makes them disappear; local breatmenl often suffice* to cure them. 
 
 We must recognize, however, thai the specific action of mercury 
 Is not perfed . Certain manifestations are bul slighl ly modified under 
 its influence. The generalized disturbances of the secondary period, 
 syphilitic, fever, syphilitic anemia, pseudochlorosis, and secondary 
 cephalalgia fm|u<Mitly resist Its action. Likewise, more profound 
 manifestations, tubercular and pustular syphilides, and precocious 
 gummata require complementary treatment. Finally, at a late 
 period, mercury is insufficient. In all such cases recourse should 
 be had to another specific, advised for the firsl time in L836 by 
 Wallace (of Dublin), and the indications for which have been well 
 regulated by Ilicor. We refer to iodine in the form of iodide of 
 potassium. Thus we have two specifics for one disease, and, a fact 
 of particular interest, each of these substances has its peculiar indi- 
 cations, so that they must be employed successively or in conjunc- 
 tion, as the case may be. 
 
 The iodide is not infallible. There are cases on record in which 
 treatment regularly followed produced no effect. The author ob- 
 served a young man suffering from an indurated chancre. Being 
 the relative of a very distinguished physician, he was treated from 
 the very beginning and submitted to mercurial medication. Two 
 years later he suffered from ocular disorders. One of the ablest 
 ophthalmologists of Paris prescribed the mixed treatment for him. 
 Instead of the improvement expected from an energetic treatment, 
 symptoms of spinal syphilis made their appearance. In spite of all 
 the medication employed, in spite of the iodides, in spite of mercury 
 injected in the form of cyanide into the veins, the paralysis followed 
 an ascending course, and terminated fatally with the appearance of 
 bulbar phenomena. Facts of this kind are rare, but are not alto- 
 gether exceptional. In the presence of them doubt has been ex- 
 pressed as to the efficiency of mercury and potassium iodide. The 
 doubt is not well founded. Treatments, even when specific, do not 
 always succeed. Clinical phenomena are too complex to be covered 
 by a single formula explaining their entire evolution. Deaths occur 
 
680 INFECT JO US DISEA SES. 
 
 from syphilis in spite of mercury and iodide, as people die from 
 diphtheria in spite of antidiphtheritic serum. We have reason to 
 be highly satisfied that it is possible to cure the great majority of 
 sufferers. 
 
 It is hardly necessary to say that specific treatment has no action 
 upon the common lesions consecutive to syphilitic lesions. Although 
 it may still improve certain scleroses, it is evidently incapable of 
 removing lesions produced by stricture or obliteration of arteries, 
 fibrous cicatrices, and foci of softening. 
 
 We need not dwell at length upon the necessity of having two 
 specifics for one disease. One hypothesis alone seems plausible. It 
 may be admitted that the agent of syphilis undergoes profound modi- 
 fications within the organism which it has invaded. Although very 
 virulent in the beginning, as is evident from the contagiousness of 
 the primary and secondary manifestations, the agent gives rise only 
 to superficial lesions. Later it possesses very slight, if any, virulence, 
 and yet at this period of its evolution it seems to be more dangerous 
 for the organism. It becomes localized at various points and pro- 
 duces reactions unlike those of the former periods. There seems to 
 be no apparent analogy between a papular syphilide and a gumma. 
 The reason the reactions of the organism which produce the lesion 
 are so dissimilar is evidently that the parasite is modified or that the 
 organism, being gradually impregnated with the toxins, has under- 
 gone a profound transformation. In the two cases, the manifesta- 
 tions being no longer analogous, the necessity of two different treat- 
 ments is readily conceivable. 
 
 We must here recall that iodine is not a specific for syphilis alone. 
 Without speaking of its action upon scrofulosis, there is another 
 infection in which iodine is a specific, namely, actinomycosis. 
 Thomasses, of Utrecht, was the first to show that potassium iodide 
 may cure actinomycosis in animals. Nocard made it known in 
 France. Then successful attempts were made in man by Van Hersen 
 and others. Netter, Duguet, and Ducor have reported interesting 
 observations. The favorable effects usually become manifest when 
 phenomena of iodism appear. 
 
 Salicylic Acid. Salicylic acid and its derivatives are often spoken 
 of as specifics for acute articular rheumatism. 
 
 Maclagan tried salicin in 1874. He started from the idea that the 
 willow, growing in damp countries, where rheumatism is frequent, 
 must contain some antirheumatic substance, since cinchona, which 
 
THERAPEUTICS OF INFECTIOUS DISEA8E8, C,H] 
 
 grows in malarial countries, contain a febrifuge sub tance. Bu 
 called attention bo salicylic acid. Strieker showed the good <■' 
 of the substance (1876), for which Senator Bub tituted salicylate of 
 soda. At present the lasl named medicine and certain similar sub- 
 stances, such as salol, salipyrine, Balophen, and aspirin, are employed. 
 Methyl salicylate is used for external applications. 
 
 All these preparations give excellent re nil . Are they, • 
 true specific medicaments? A greal many authorities so believe, and 
 argue that those arthrites which resisl the action of the medicine are 
 not truly rheumatic. In fact, il is certain thai the arthropathy 
 secondary infections, notably gonorrheal arthropal nies, are nol bene- 
 fited by salicylates as are the arthropathies of acute articular rheu- 
 matism. This is an argumenl in supporl of the specific character. 
 II, has been objected thai the visceral manifestations occurring in the 
 course of their evolution arc not modified, bu1 we have -ecu analog 
 results in many other oases. Specific serums are likewise powerless 
 to remedy certain visceral evolutions, such as nephritis and parab 
 We may, therefore, class the salicylates among the specific medicine-, 
 although it must be acknowledged that we are completely ignorant 
 of their mode of action. 
 
 If we now consider the four specific medicines, we see that one 
 of them — quinine — acts as a parasiticide, and that the other three 
 possess an influence the mechanism of which remains unknown. 
 
 Bacteriotherapy. 
 
 Bacteriotherapy is a therapeutic method aiming to combat infec- 
 tion by infection, viz., to introduce virulent agents or microbic toxins 
 into the diseased organism. 
 
 It has been long known to clinical observers that erysipelas may 
 cause torpid infectious lesions to retrocede and disappear. Ulcers, 
 lupus, syphilitic lesions, and cancer have been seen to improve and 
 heal under the influence of an intercurrent erysipelas. It may. 
 therefore, be questioned whether, in certain cases, it would not be 
 advisable to inoculate disease for therapeutic purposes. Ricor 
 made the first attempt of this kind in syphilis. The method proved 
 unsuccessful, and experiments of this nature have only recently 
 been taken up. Following Fehleisen. several physicians injected 
 cultures of living and virulent streptococcus into patients suffering 
 from cancer. The procedure was a dangeious one. Several of the 
 patients thus treated succumbed. Nevertheless, inoculation of 
 
682 INFECTIO US DISEASES. 
 
 virulent products is still employed in one case, namely, in the treat- 
 ment of pannus; the introduction of gonorrheal pus induces a 
 purulent conjunctivitis which is sometimes followed by a cure. 
 
 While virulent microbes are dangerous, non-pathogenic microbes 
 may be introduced with apparent safety. An attempt has been 
 made to treat tuberculosis by inhalations of the bacterium termo. 
 The results were negative, and the procedure was abandoned. A 
 therapeutic measure has recently been resorted to which enters the 
 domain of bacteriotherapy. We refer to the ingestion of beer yeast 
 against suppurative cutaneous inflammations and notably furuncu- 
 losis. 
 
 This method, which was indicated as early as 1852 by an English 
 physician, Mosse, is a popular remedy in the north of France. 
 It has been employed by Debouzy, Gobert, and De Backer. It is 
 only since the work of Dr. Brocq, however, that attention has been 
 drawn to this subject. The investigations of this author show that 
 by giving to a patient one teaspoonful of fresh yeast three times a 
 day we ma)^ arrest the development of furuncles, suppress pain, and 
 hasten cicatrization. It is not exactly known how the yeast acts. 
 It probably produces its effect by regulating digestion, which is so 
 often disturbed in these patients. 
 
 The employment of living microbes for therapeutic purposes seems 
 to have a rather restricted field. As microbes do not act except 
 by their soluble products, it may be questioned whether toxins 
 might not render the same therapeutic service. We must consider 
 two quite different cases. We may combat an infection by means 
 of products originated by microbes different from the one which 
 we wish, to antagonize. On the other hand, we may employ the 
 toxins secreted by the pathogenic microbe which we wish to attack. 
 The former method is very much like bacteriotherapy, which has 
 already been studied. There are some experiments in its support. 
 When speaking of microbic associations we alluded to the fact that 
 pyocyaneus toxins hinder the evolution of anthrax. Sterilized 
 cultures of the bacillus prodigiosus act in the same manner, at 
 least in rabbits. Kostiurine and Krainski have shown that putrefied 
 fluids combat anthrax and tuberculosis. Therapeutic attempts were 
 made on man. Rumpf and Kraus have treated typhoid cases by 
 sterilized cultures of the bacillus pyocyaneus. 
 
 Streptococcic Toxinotherapy. Cultures of the streptococcus 
 have been the subject of the greatest number of researches. Lassar, 
 
THERAPEUTICS OF TNFE0TI0U8 DISEASES. 683 
 
 Spronck, Coley, Friedreich, Kocher, and R4pin treated a certain 
 number of neoplasms by means of streptococcic toxin and obtained 
 a few successes, especially in cases of sarcomata. The procedures 
 
 employed |>y these various observers were not, however, alwayfi the 
 
 same. 
 Lassar, 1 fearing the use of simply filtered cultures, the high 
 
 toxicity of which we h.-ive proved ;is regards animals, resorted to 
 cultures sterilized by heal and freed from all figurate elements by 
 means of filtration through porcelain. The greatesl pari of the 
 
 noxious substances is thus destroyed, and the fluid is not toxic 
 unless it is derived from an extremely virulent culture. Taking 
 ground upon the same experimental facts, Spronck* also tried the 
 heated cultures. Believing, however, t hat the toxic substances 
 would be more active from a therapeutic standpoint, he employed 
 a mixture of heated and simply filtered cultures. Etepin" employed 
 filtered but not heated cultures. Finally, Coley,' inspired by our 
 investigations on microbic associations, utilized a mixture of strepto- 
 coccic toxins and sterilized cultures of the bacillus prodigiosus. 
 Not only the composition of the fluid, but also the mode of injection 
 varied. While Lassar and Coley injected the toxins into the interii ir 
 of the tumors, Spronck and Repin injected them at a distant point, 
 and Repin finally introduced them into the veins. These various 
 procedures having given a few successes in the treatment of neo- 
 plasms, we, with Dr. Hallopeau, 5 pursued analogous researches upon 
 lupus. It seemed to us, however, that our first duty was to begin 
 with harmless fluids — i. e., to try streptococcic cultures sterilized 
 by heat. 
 
 We operated in the following manner: Bouillon containing a 
 streptococcus of medium virulence was kept in the incubator for 
 fifteen days. At the end of this period the culture was evaporated 
 and reduced to one-sixth of its original volume, then heated in the 
 autoclave to 230° F. (110° C.) for fifteen hours. The culture was not 
 filtered, in order that we might use both the toxins modified by heat 
 
 1 Lassar. Zur Erysipclimpfung. Deutsche med. Wochenschrift. 1S91. Xo. 29. 
 
 2 Spronck. Tumeurs malignes et maladies infectieuses. Annales de l'Lnstitut Pasteur, 
 1S92, p. 6S3. 
 
 3 Repin. La toxithe>apie des tumeurs malignes. Revue de chirurgie, June, 1S95, 
 p. 465. 
 
 4 Coley. Treatment of Inoperable Malignant Tumors with the Toxin of Erysipelas 
 and the Bacillus Prodigiosus. American Journal of the Medical Sciences. July. I - 
 
 6 Hallopeau and Roger. Action des toxines streptococciques sur le lupus. La presse 
 m£dicale, April S, 1S96. 
 
684 INFECTIOUS DISEASES. 
 
 and the microbic cadavers. The fluid thus obtained is almost 
 inoffensive. Guinea-pigs, rabbits, and mules received considerable 
 amounts without presenting any notable disturbance. We kept for 
 two years a rabbit which had received 400 c.cm. of sterilized 
 streptococcic toxins and which continued in good health. It 
 seemed, therefore, that the fluids were not apt to give rise at 
 the end of a certain period of time to any organic disturbances or 
 visceral lesions. The only phenomena produced in the animals by 
 subcutaneous injections were tumefaction at the point inoculated 
 and sometimes a transitory rise in temperature. There are some 
 exceptions, however, to this rule. An animal may manifest an 
 active reaction, while other animals present no disorder whatever. 
 We observed a mule in which each injection of the toxin produced 
 fever, profuse sweating, and lassitude, while other mules similarly 
 inoculated showed no reaction. The same individual peculiarities 
 are more markedly observed when man is experimented upon. 
 
 Our therapeutic inoculations, which were practised upon seven 
 women, were all made into the diseased regions, beneath the skin. 
 We began by injecting five or six drops of the fluid, representing 
 thirty to thirty-six drops of the primary culture; then, if the sensi- 
 tiveness of the patient was not too great, we gradually increased 
 the dosage. We finally introduced as many as thirty drops of 
 toxins at one sitting, about 9 c.cm. of the culture. The injection 
 generally caused a sufficiently strong local reaction. An edematous 
 tumefaction, a true fluxion, was generally produced, which set in 
 from fifteen minutes to two or three hours after the injection. The 
 edema was in some cases sufficiently intense to disturb the patient 
 and notably to cause closure of the eyelids, or to embarass move- 
 ment of the lips. At the end of a few hours, however, the symptoms 
 improved, and within a day or two the edema disappeared alto- 
 gether. These local manifestations evidently vary according to the 
 amount introduced. Individual predisposition, however, seems to 
 play the principal role in their production. In one of our patients 
 the smallest injection gave rise to tumefactions which, at first, 
 seemed quite disquieting. In spite of the local disorders, the general 
 phenomena were not very pronounced. A few patients complained 
 of malaise and lassitude, several of lumbar pains for a day or two. 
 Contrary to what has been noted by other observers, however, we 
 noticed no veritable fever. The temperature, carefully taken every 
 hour, did not rise above 99.5° F. (37.5° C). Only once a patient 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 685 
 
 developed a temperature of 104° r. (40° C). The intere ting fad 
 in this case was that the hyperthermia was produced a1 the end of 
 two months of treatment, while previous injections of practically 
 the same amounts had given rise to no fever, nor did subsequent 
 
 inoculations. 
 
 II, did not seem to us that a well marked habil to the toxin* 
 produced. The Local phenomena were nearly always the Bame in 
 the same patient. In the woman who i resented 3uch a remarkal le 
 susceptibility the reactional swelling was produced al the end of 
 
 nine months of treatmenl just as on the first day. This result, 
 which differs notably from tint obtained by other experimenters, 
 is due, perhaps, to the presence of inicrobic radavers in the liquid 
 employed, perhaps to the relatively long interval between the 
 
 injections; in fact, the hit lei' were given only once ;i week. 
 
 The action of sterilized cultures of the bacillus prodigiosue 
 quite different. This microbe was cultivated in bouillon, then, at 
 the end of eighl days, the culture was sterilized at a temperature 
 of 230° F. (110° C.) for ten minutes and injected without being 
 filtered. The fluid thus prepared, mixed with the streptococcic 
 culture, was tried on four patients. We began by introducing three 
 drops of the culture of bacillus prodigiosus. This minute dose cause* 1 
 accidents which somewhat alarmed us, at least with regard to two of 
 the patients. Three hours after the injection violent chills occurred, 
 the extremities became cold, the pulse was weak and rapid, the 
 central temperature rose to 102.2° F. and to 103.1° F. (39° and 
 39.5° C); these symptoms were followed by nausea, vomiting and. 
 in one of the patients, diarrhea with incontinence of feces. These 
 disorders, however, were only transitory. On the following day the 
 patients simply felt tired. The crisis terminated in a very profuse 
 herpes labialis. Instructed by these results, we introduced only two 
 drops of the culture for the second injection. The symptoms con- 
 sisted in a slight malaise and an insignificant rise in temperature. 
 Subsequently the patients became habituated to the toxin, and 
 received progressively increasing doses — as many as six drops — 
 without presenting any appreciable reactions. 
 
 The action of the bacillus prodigiosus demonstrated far better 
 than all laboratory experiments that a minute dose of toxin may 
 give rise to extremely grave general manifestations, and clearly 
 establishes the toxi-infectious origin of herpes. Lastly, it is very 
 interesting to note that the soluble products of the bacillus pro- 
 
686 INFECTIOUS DISEASES. 
 
 digiosus and non-pathogenic microbes proved far more toxic than 
 those of the streptococcus. The differences were very remarkable. 
 Three drops of the bacillus prodigiosus produced disquieting symp- 
 toms, while thirty drops of a streptococcic culture, representing 
 9 c.cm. of the primary culture, produced only a local reaction. 
 Sterilization, however, had been made according to the same pro- 
 cedure, viz., by heat at 210° F. (110° C). 
 
 If now we consider the results obtained in our seven patients 
 we find that in one lupus was completely cured. In two a very 
 marked improvement was produced; in the other four, amelioration 
 was slight or nil. The best results were obtained in young subjects, 
 whose vital reaction is more energetic and more readily aroused, 
 and in those whose lupuses were characterized by fungous, vegetat- 
 ing tubercles and deep and extensive ulceration. Under the influ- 
 ence of the treatment the tubercles were reduced, the discharges 
 disappeared, and the ulcerations rapidly diminished. Finally, there 
 was produced a cicatrix remarkable for its perfect elasticity; it was 
 almost normal skin. On the other hand, the result was slight or 
 negative in those cases in which sclerosis dominated and the tubercles 
 were embedded in cicatricial tissues. All that was observed in such 
 patients was a reduction in the size of the tubercles and disappear- 
 ance of a few. 
 
 The results obtained by us will, perhaps, not appear very encour- 
 aging. The patients, however, manifested great enthusiasm with 
 regard to these therapeutic attempts. In despair at the failure of 
 other methods, the sufferers were satisfied with the amelioration 
 obtained at our hands. The reason we did not further pursue our 
 attempts is that microbic toxins are such actively energetic sub- 
 stances that one cannot exercise too much prudence when applying 
 them to human therapeutics. We would not have made even the 
 attempts above reported had we not been led to do so by laboratory 
 investigations and by results obtained in the treatment of cancer. 
 At all events, we watched the patients with the greatest care. We 
 repeatedly examined their urine and we prolonged the experiment 
 because we noticed no permanent disorder and no albuminuria. 
 The results obtained did not seem to us, however, sufficiently satis- 
 factory for continuing our therapeutic attempts. Nevertheless, we 
 thought it might be of value to make known our researches in the 
 hope that, if taken up by others with some technical modifications, 
 they would lead to a better method. The method should be so 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 687 
 
 modified ;is to increase the local action and i" Buppre the general 
 manifestations. In fact, it seems thai tli'' toxin acl by the inflam- 
 mation induced by them; and it i for thi rea on thai we injected 
 them into the diseased tissue itself. Whal proves thai we 
 right in so doing is the fad thai in ;i case of bilateral lupus the 
 inoculated side rapidly improved, while the oppo ite ide pre ented 
 bill slight modification. Moreover, for fear of accidents, we made 
 only one injection per week. It is better t<> make one every two 
 or three days. Lastly, our observations showed thai the addition 
 of soluble producls of Hie b;ieillus |trodigiosus render the fluids 
 much more efficacious. In ;i ca.se in which the Streptococcic toxins 
 were employed alone the results were almosl nil. Each injection 
 however, produced very m:irl«-d edema in the patient. For this 
 reason we did not add the bacillus prodigiosus, and noted thai 
 fluxions caused by the streptococcus alone were not sufficient to 
 ameliorate lupus. Likewise, in the patient who recovered and in 
 those who notably improved, the favorable effects were not very 
 clear until after the mixture of the two toxins was employed. 
 
 It is not, however, to be concluded that these microbic products 
 possess specific germicidal power. The toxins probably act not 
 upon the bacillus, but upon the organism. They stimulate the 
 responsive activity of the economy and attract to the diseased spot 
 serum and leucocytes which combat the bacilli and the morbid tissue 
 developed under their influence. 
 
 While the results obtained are not sufficiently successful to 
 warrant a systematic continuance of the bacteriotherapic method, 
 it would be reasonable to try it in certain suitable cases, viz.. in 
 young persons suffering from fungus and ulcerating forms of lupus. 
 We are aware that cases of this variety are most frequently cured 
 by classical procedures. When, however, the latter fail, a last 
 attempt may be made by means of the toxins. It is well to repeat 
 that it is necessary to increase the therapeutic effects by practising 
 the injections at shorter intervals and by employing more active 
 fluids, or by making use of a serum analogous to that which was 
 employed by Emmerich and Scholl in the treatment of cancer. 
 
 Streptococcic Hematoxin. Instead of a culture, Emmerich and 
 Scholl employed the serum of infected animals. One might suppose, 
 in fact, that active toxins would be found therein in greater abun- 
 dance. 
 
 The serum of sheep infected with the streptococcus was filtered 
 
688 INFECTIOUS DISEASES. 
 
 through porcelain in order to free it from all living elements. This 
 serum was injected into neoplasms in doses varying from 1 c.cra to 
 25 c.cm. The injections produced at the point of inoculation a red- 
 ness analogous to that of erysipelas, which persisted for a day or two. 
 A febrile movement was at the same time observed. It is to be 
 noted that the more intense the local reactions the better were the 
 effects produced. Such is precisely the case when sterilized cultures 
 are made use of. The serum proved inefficient in only two cases. 
 In the other patients the more recent the tumor the greater was 
 the activity of the serum. Its employment is advisable in cases 
 of postoperative relapses. 
 
 The report of Emmerich and Scholl was too important not to 
 immediately give rise to control researches. Unfortunately, the 
 results obtained by other experimenters were not confirmative. 
 Some of them, Schuler among others, reported successes, but the 
 majority of physicians obtained no appreciable results, and some 
 of them even observed accidents. Burns found the patients feverish 
 and dyspneic, the heart weakened and the urine albuminous. In 
 spite of the answers given by Emmerich and Scholl to criticisms, 
 their method is to-day abandoned. It does not seem to be superior 
 to bacteriotherapy, and it has the disadvantage of being more 
 complicated and, what is of greater consequence, more dangerous. 
 
 Tuberculin. The method that consists in treating an infection 
 by the soluble products engendered by the pathogenic agent which 
 is to be combated differs considerably from the toxinotherapic 
 procedure above studied. The latter is based upon experimental 
 data; such is not the case with the former. In fact, numerous 
 investigations have demonstrated that microbic products favor the 
 development of the microbe which has secreted them. . Although 
 they are often endowed with vaccinating power, they are never 
 curative. Perhaps it will some day be possible to prepare a sub- 
 stance possessing therapeutic properties by modifying these prod- 
 ucts. This is what Smirnow claims to have obtained by subjecting 
 diphtheritic toxin to electrolysis. 
 
 Microbic products have been utilized in the treatment of three 
 diseases— tuberculosis, glanders, and typhoid fever. 
 
 The enthusiasm with which the first communication of Koch was 
 met is well remembered. At the Berlin Congress of 1890 the eminent 
 scientist announced that he had succeeded in arresting the evolution 
 of tuberculosis in animals by means of a product which was called 
 
THERAPEUTICS OF TNFEOTI0U8 DI8EA8E8. 
 
 tuberculin or Koch's "lymph." If can be prepared by reducing 
 bo one-tenth of its volume a culture of tubercle bacilli developed 
 in glycerinated peptonized veal bouillon, When filtered through 
 porcelain it is obtained in the form of s limpid and brownish fluid, 
 the composition of which is evidently quite variable. Hence, \\ 
 should not be employed excepl after its action ha been verified 
 upon tubercular guinea-pigs. 
 
 Like oilier microbic products, tuberculin act* only when ii i 
 injected beneath the skin or into the veins. When introduced by 
 the alimentary canal it has no effect. Us action is not very marked 
 upon animals; a guinea-pig easily resists 2 c.cm. of the "lymph," 
 while ;i dose of 0.25 c.cm. produces notable effects in man. Bj 
 reducing the results to the same unit of weight, it nmy be .-ecn 
 that man is from 1000 to 1500 times more sensitive to this remedy 
 than the guinea-pig. Therefore, the action of tuberculin should 
 be studied upon man. Koch had the courage to experimenl upon 
 himself. He injected 0.25 c.cm. of the "lymph" into his arm. 
 Three or four hours later he experienced twitchings in his limbs 
 and paroxysms of coughing; later on, chills, nausea, vomiting, and 
 fever attaining 102.2° F. (39° C). At the end of twelve hours 
 the morbid phenomena disappeared, except a slight tired feeling. 
 
 In a healthy man or in individuals suffering from a non-tubercular 
 affection, it is necessary to employ at least 0.01 c.cm. of lymph in 
 order to produce disturbances. The temperature, rises to 100.4° F. 
 (38° C). In tuberculous subjects 0.003 c.cm. and even 0.002 c.cm. 
 suffices to arouse intense reactions. 
 
 In his first communication Koch reports an experiment which 
 seems to have been the point of departure of his investigations. He 
 asserted, contrary to Dr. Arloing, that, in a tubercular guinea-pig, 
 a reinoculation of the virus gives rise to only slight lesions without 
 any tendency to generalization. It would be inferred from this fact 
 that a first inoculation confers a certain degree of immunity. Hence 
 it was natural to investigate whether the soluble products of the 
 tubercle bacillus, like those of a great number of bacteria, would not 
 act in the same manner. Koch claimed to have obtained this result, 
 but he indicated it only incidentally without relating any experiment. 
 Arloing, Rodet, and Courmont took up the question. They pursued 
 a great number of researches on this subject and constantly failed. 
 The animals were never rendered immune: on the contrary, at times 
 they manifested a morbid receptivity and succumbed more rapidly 
 
 44 
 
690 INFECTIOUS DISEASES. 
 
 than the controls. The same failure attended the experiments of 
 Jaccoud, Dujardin-Beaumetz, and Dubief. It may, therefore, be 
 said that, with respect to this second point, Koch's tuberculin failed 
 to realize what had been promised by its inventor. 
 
 The question of greater consequence is, however, the therapeutic 
 action of the lymph. In this regard, Koch teaches us that small 
 amounts of the lymph are capable of killing tubercular guinea-pigs, 
 while, by diminishing the doses, it is possible to cause reactions 
 followed by a notable amelioration. Are the guinea-pigs cured, how- 
 ever? How long do they survive? What happens as a result of 
 these injections? May not these injections cause grave and tardily 
 supervening accidents, as the experiments of Maffucci tend to show? 
 These are questions requiring answers. Such information is indis- 
 pensable before the application to man of a remedy so active and 
 so dangerous. 
 
 According to Koch, the lymph is to be used for therapeutic pur- 
 poses in the following manner: In cases of pulmonary tuberculosis 
 very small doses should be injected at first; in fortunate cases amel- 
 ioration is rapidly produced. Cough diminishes, the expectoration 
 assumes a mucous character, the general state is improved, the 
 bacilli decrease and finally disappear. This result may be obtained 
 in four or six weeks, at least, in patients suffering from the first stage 
 of the disease. According to Koch, such patients can certainly be 
 cured. Even, however, when the disease has reached the stage of 
 excavation and the lung is invaded by innumerable pyogenic mi- 
 crobes, the treatment may still produce some amelioration. 
 
 By studying more closely the modifications occurring in tubercular 
 foci it may be seen that the lymph acts upon the tissues, provided 
 the latter be yet living and impregnated with toxin. The bacilli are 
 not reached and are simply rejected with the neighboring parts. 
 Be that as it may, the chief action of the lymph is upon the tissues 
 surrounding the tubercles, and the mechanism of this action was 
 demonstrated by Bouchard's experiments. This author found that 
 tuberculin acts by exciting the vasodilator centre. If the fundus of 
 the eye of the rabbit, into which this substance has been injected, 
 is examined an active dilatation of the vessels is observed (hence the 
 name ectasin, given by Bouchard to the lymph). This dilatation 
 persists for several hours. If, however, a vasoconstrictor substance 
 or anectasin (for example, the sterilized culture of the bacillus pyo- 
 cyaneus) be injected into a rabbit thus prepared the papilla becomes 
 
THEEAPEUTIOB OF INFECTIOUS DI8EA8E8. *;!>) 
 
 anemic; then, at the end of half an hour, the action of the anectasin 
 having ceased, that of ecta in i again manifested and th< 
 dilate. The same phenomena occur around those tubercular foci 
 which, in consequence of the vb omotor dilatation, are the seal of a 
 profuse exudation of serosity and of an active diapedesis (Kromi 
 Cornil). The neoplastic tissue re i I . or it i econdarily affected 
 (coagulation necrosis, suppuration, fatty degeneration) and mi 
 eliminated. In the case of an ulceration occupying a mucous mem- 
 brane, it becomes I ransformed into a simple wound and covered with 
 granulations of a benign nature (Jurgens). Moreover, Koch has 
 remarked that successive injections arouse le and I' violent reac- 
 tions. In his opinion this result is not due to the formation of habit, 
 but to the progressive disappearance of diseased tissues. When all 
 the neoplasms are eliminated, reaction becomes similar to thai which 
 is presented by a healthy individual. Lei us note, however, thai in 
 certain oases the sensitiveness of the patient increases with each new 
 inoculation. In other instances, habil is established long before the 
 elimination of the diseased parts. 
 
 Before considering the results obtained by various physicians who 
 have experimented with tuberculin, we must briefly indicate the 
 principal dangers to which this medicine exposes the subjects. 
 
 These dangers are at times dependent upon a general intoxication : 
 at times upon a too intense local reaction. Thus, as regards the 
 respiratory apparatus, pulmonary edema and edema of the glottis 
 (which has in some cases proved fatal by suffocation), hemoptysis, 
 pleural effusions, and bronchopneumonias have been observed. In 
 other cases auscultation has revealed an aggravation of the physical 
 signs connected with the pulmonary lesions, which have sometimes 
 caused death. Virchow has dwelt upon these lesions, which he desig- 
 nated as " injection pneumonia," and which consist essentially of a 
 phlegmonous process which causes rapid destruction resulting in pul- 
 monary excavations. Coincident ly, new small tubercles appear, 
 which are due to a "mobilization" of the bacilli. A more or less 
 torpid tuberculosis may thus rapidly terminate by generalization of 
 the infection and development of an acute miliary tuberculosis. 
 Experimenters who have studied the action of therapeutic doses of 
 the lymph in tubercular guinea-pigs have often observed similar 
 effects. In this connection, nothing is more instructive than the 
 researches of Arloing and his collaborators. The lymph hastened 
 generalization, and at times it caused this condition in animals 
 
692 INFECTIOUS DISEASES. 
 
 inoculated with an attenuated virus which produced only local 
 lesions. 
 
 Intense visceral congestions are found at the necropsy of animals 
 killed by tuberculin injections. The same phenomena are observed 
 in man. Thus, there are on record hemorrhagic nephrites, renal 
 congestions, expressed by albuminuria or hematuria, In a case of 
 Rosenbach's the patient suffered from an almost complete anuria; 
 in twenty-four hours he voided 50 c.cm. of urine of a mahogany 
 color, which was transformed into a solid mass by the addition of 
 nitric acid. In children suffering from tubercular meningitis the 
 use of the tymph gave rise to acute edema of the meninges, which 
 hastened the fatal termination. Lastly, under the influence of this 
 medicine, intestinal ulcerations have been seen to end in perfora- 
 tion. 
 
 Among the manifestations ascribable to a general intoxication 
 some are devoid of gravity. Such are various eruptions, leucocy- 
 tosis, albuminuria, urobilinuria (Cavallero), and peptonuria; the last 
 symptom is surely due to the medicine itself, since it has been 
 observed in healthy individuals (Kahler), or in normal animals 
 (Bouchard). In other cases the phenomena are more serious. Tran- 
 sitory delirium or even permanent psychoses occur (Jolly). Angina 
 pectoris, loss of consciousness, coma, and, finally, a tendency to cardiac 
 collapse with cyanosis, cold extremities, weak and irregular pulse 
 may supervene. Even permanent lesions of the endocardium may 
 occur (Hallopeau). 
 
 The remedy is well borne only in those cases in which the altera- 
 tions are superficial and the mortified tissues can easily be eliminated. 
 In fact, accidents are rarer when the lymph is employed against 
 cutaneous tuberculosis or tuberculosis of the conjunctiva, nose, 
 mouth, and intestine. Its action on the larynx must be very care- 
 fully watched. Finally, as regards the lungs, it may be employed 
 only when the lesions are not far advanced or when the cavities 
 communicate largely with the bronchi. It is well to remark that if 
 the diseased tissues cannot be eliminated by expectoration no favor- 
 able results can ever be obtained. In cases of articular tuberculosis 
 Prof. Cornil observed enormous painful swelling in the diseased 
 joints. At the end of a certain period of time these manifestations 
 improved, but there was no amelioration of the disease. On the other 
 hand, good results were obtained in a few cases in which surgical 
 intervention was resorted to. 
 
THERAPEUTIOB OF INFECTIOUS DI8EA8E8. 693 
 
 Are fche dangers accompanying injection of the lymph compen- 
 sated l>y fche benefits derived by fche patient? At present this que - 
 tion can be answered in a deci ive manner. Even in external tuber- 
 culoses, amelioration, when any has occurred, has been mostly rela- 
 tive and transitory. In cases of lupus /. e. f in instance in which 
 the best results ;irc obtained -only the superficial nodules are elim- 
 inated; the deep-seated ones persist, and the patients Boon - 
 to present any more reaction al the diseased point, even when 
 doses of 0.08 c.cm. are employed. In this connection, nothing i- ■■>- 
 instructive as the perusal of the reporl prepared by Dr. Besnier 
 in the name of the St. Louis Hospital Commission. It regards the 
 treatment of thirty-eight cases of lupus. Improvement frequently 
 occurred, especially in the open forms of the disease, bu1 this im- 
 provement was not permanent, and the affection resumed its course. 
 At times it was aggravated. Thus, even in cases of attenuated tuber- 
 culoses, Koch's treatment is often inefficient. In other cases it may 
 prove dangerous. The use of the lymph was therefore gradually 
 abandoned. 
 
 It would, however, be unjust to wholly condemn the method. 
 Although tuberculin, taken as a whole, is more harmful than other- 
 wise, it may be hoped that it will some day be possible to separate 
 the curative substances contained in it. This is what Koch, with the 
 assistance of Proskauer and Brieger, has attempted. The substance 
 which he obtained, however, produces the same dangerous effect- as 
 the raw tuberculin, and is no more to be recommended than the 
 former. W. Hunter announced in the London Congress of 1895 that 
 he had isolated from tuberculin three active substances: the first 
 one, of an albuminoid nature, is hyperthermizing : the other two are 
 albumoses, one of which possesses a phlogogenic power, the other 
 exerts a curative action. Klebs, Kuhne, and Rohmer have pur- 
 sued similar researches. 
 
 In a more recent communication Koch indicated a new prepara- 
 tion of tuberculin: The desiccated bacilli are triturated in an agate 
 mortar with a pestle of the same substance. The magma is taken 
 with a little water and is centrifuged for thirty to thirty-five minutes. 
 The fluid obtained is tuberculin 0, which is analogous to the old raw 
 tuberculin. It possesses no therapeutic properties. The residue is 
 then taken, dried, and again triturated, and. after having added water 
 to it, is again centrifuged. When this operation has been repeated 
 several times almost all the precipitate is exhausted and a series of 
 
694 INFECTIOUS DISEASES. 
 
 fluids obtained which are mixed together. Thus is obtained tuber- 
 culin R, which, unlike tuberculin 0, contains substances insoluble in 
 glycerin. This new tuberculin is germicidal, it causes no abscesses, 
 and possesses immunizing and curative properties. No febrile reac- 
 tion is said to occur. 1 
 
 The first control researches due to Letulle and Peron 2 have hardly 
 been favorable to the method. Its only advantage is that it is not 
 dangerous. 3 Judging, however, by the small number of facts thus 
 far published, it does not seem that we as yet possess the specific 
 remedy of tuberculosis. 
 
 Mallein. The discovery of tuberculin led bacteriologists to look 
 for analogous substances in other cultures. Thus, Helman and 
 Kalning prepared a substance, mallein. This product is hardly ever 
 used for any other than diagnostic purposes. According to Bonome 
 and Vivaldi, even minute doses cause death in cats suffering from 
 glanders, while they produce amelioration in guinea-pigs, rabbits, 
 and man. As to the horse, numerous experiments seem to demon- 
 strate that mallein may favor cicatrization and at times bring about 
 a recovery, at least when the lesions are recent and discrete. 
 
 A last attempt was made with reference to typhoid fever. E. 
 Fraenkel treated patients with sterilized cultures of Eberth's bacillus. 
 The first effect is a rise in the temperature, followed by an at least 
 temporary fall. The statistics published by the author seem quite 
 encouraging. 
 
 Serumtherapy. 
 
 The discovery of serumtherapy, the way to which was prepared 
 by the researches on the germicidal properties of the fluids of the 
 organism and by the efforts of experimental therapeutics, due to 
 Drs. Richet and Hericourt, belongs, as is known, to Behring and 
 Kitasato. Having recognized that the serum of animals vaccinated 
 against diphtheria is antitoxic they were led to employ it for thera- 
 peutic purposes. 
 
 After the data reported in the preceding chapter we may readily 
 comprehend the radical difference separating bacteriotherapy from 
 
 1 Koch. Ueber neue Tuberkulin Praeparate. Deutsche med. Wochenschrift, August 
 1, 1897. 
 
 2 Letulle and Peron. La nouvelle tuberculine de Koch. La presse m^dicale, August 
 21, 1897. 
 
 3 Borquier. La nouvelle tuberculine R et son emploi, en particulier dans la tuber- 
 culose pulmonaire. Th6.se de Paris, 1897. 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 
 
 serumtherapy. The aim of the former method i to acl with the 
 products secreted by microbes, that of the second i to di cover in 
 the blood not what remains of the toxins introduced, but the prin- 
 ciples which are developed under its influence. Serumtherapy 
 
 employs materials elaborated by the organism itself in r 
 against infection. It is therapeutic and vaccinating alike, bul the 
 immunity which it confers is a passive immunity. The organism 
 takes no part in its production; if makes no effort : it simply allows 
 itself to be impregnated by the substances introduced. On the other 
 hand, bactcriotherapy is ol'lener preventive than curative. It pro- 
 duces immunity, but by means of an altogether different mechanism. 
 It is a process of active immunity dependent upon an efforl of the 
 organism. 
 
 Choice of the Animal. It was formerly believed thai the more 
 sensitive the organism was to the disease the better it reacted. This 
 idea, led authors to vaccinate the most susceptible animals. At pres- 
 ent it seems to be demonstrated lhat, although the law is real, it is 
 subject to numerous exceptions and that it is possible to confer active 
 immunity whether the animals are naturally refractory or not. We 
 have proof of this in what occurs in diphtheria. Behring believed 
 that an animal sensitive to the virus should be employed, and he 
 experimented upon sheep. Roux has shown that the horse, which 
 is only slightly susceptible to diphtheria, gives just as efficacious a 
 serum. The same is true of tetanus; Roux and Vaillard have demon- 
 strated that the chicken, which does not contract this infection, fur- 
 nishes a therapeutic serum when large amounts of toxins are injected 
 into it. 
 
 It is not so much the degree of sensitiveness or natural resistance 
 of the animal as the possibility^ of easily obtaining large quantities 
 of blood and a serum devoid of toxic properties that must guide us 
 in our choice. In fact, it is known that transfusion between indi- 
 viduals of different species is not always inoffensive. Experimenta- 
 tion cannot, however, furnish decisive data to therapeutics, for the 
 toxicity of the serum of a given species varies considerably, according 
 to the species into which it is injected. It is, therefore, impossible 
 to know with sufficient accuracy what its effect would be in man. 
 Nevertheless, it is interesting to look for the solution of the problem 
 in animals. 
 
 By making intravenous injections of various serums into rabbits, 
 the following results have been obtained : 
 
696 IXFECTIO US DISEASES. 
 
 Animal Furnishing the Serum. Fatal Dose for One Kilogram of Babbit. 
 
 Cattle 8 c.em. (Runimo and Bordoni). 
 
 Sheep 12 c.em. (Runimo and Bordoni). 
 
 Calf 13 c.em. (Runimo and Bordoni). 
 
 Man 15 c.em. (Mairet and Bosc). 
 
 Chicken 20 c.em. (Runimo and Bordoni). 
 
 Horse 80 c.em. (Zagari). 
 
 Clinical facts seem to be in harmony with the data of experimen- 
 tation for establishing that the serum of the dog is not well borne, 
 while that of the horse is excellent, and may be employed in large 
 doses. The serum of the cow, which is very toxic for the rabbit, is 
 very slightly so for man. In the treatment of variola Dr. Beclere 
 injected as much as 1560 c.em. without giving rise to any disturbance. 
 Finally, it is certain that the serum of man would be the best from 
 this standpoint. It will be shown later on that it has been employed 
 in therapeutics in exceptional cases. 
 
 Vaccination of Animals. The animal being chosen, the reactions 
 of its organism must be called into play in order to increase its 
 resistance. This may be realized by three methods: 
 
 1. Inoculation of living microbes. 
 
 2. Injection of toxins produced in artificial cultures. 
 
 3. Injection of toxins derived from the diseased organism. 
 
 The first procedure exposes to certain accidents. After injection 
 of living cultures into animals the microbes may persist in the blood, 
 even when the subject seems to have recovered. For instance, the 
 antistreptococcic serum derived from animals prepared by means of 
 living cultures has sometimes caused phlegmonous erysipelas, be- 
 cause it still contained streptococci which were undoubtedly atten- 
 uated, but nevertheless capable of producing local lesions. 
 
 Of course, this danger may be avoided by employing sterilized cul- 
 tures, modified or not by physical or chemical agents. There is no 
 doubt that immunity thus created is much less durable than when 
 it results from virulent inoculations. However, it then suffices to 
 repeat the injections of toxins for maintaining or increasing the 
 properties of the serum, for it is to be noted in this connection that 
 repeated injections of small doses are more efficient than the intro- 
 duction of a single, even though greater, amount (Roux and Metch- 
 nikoff). 
 
 The animals vaccinated by means of soluble substances have 
 already been employed for the preparation of a great number of 
 serums. It is quite evident that serums may be obtained against 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 897 
 
 all the known pathogenic agents, on condition, however, thai B 
 method of vaccination can be found. For example, the rea on 
 attempts failed in tuberculosis is thai it ha ao1 yel been po ible 
 to confer upon animals a genuine immunity againsl thij infection. 
 
 The serumtherapy method may be employed even when the path- 
 ogenic agent has not been isolated. Under the e condition ,u emay 
 be made according to the requirements of the ca e of one of the 
 following procedures: 
 
 The serum from animals vaccinated by meant of more or less modi- 
 fied virulent tissue. This is done, for instance, in regard to hydro- 
 phobia. 
 
 The blood obtained after t he cure of the disease, whether the latter 
 be spontaneous or inoculated. For diseases which are nol transmis- 
 sible to animals, man is experimented upon. After hie recovery 
 blood is taken from him which is employed for reinforcing the n 
 ance of patients. This has been done notably in typhus fever, scar- 
 latina, and rheumatism. 
 
 Lastly, in the case of a non-inoculable disease, fluids or extracts 
 of tissues may be taken and injected into animals so as to arouse 
 reactions on the part of the organism. This method, which is highly 
 rational, has not yet received many applications. 
 
 It is likewise possible to employ extracts taken from organs in 
 which the toxic substances accumulate or are produced. Drs. Heri- 
 court and Richet have resorted to this procedure to prepare an anti- 
 neoplastic serum. 
 
 These various procedures render the serum efficacious because they 
 increase the resistance of the animal. This is demonstrated when 
 the disease is inoculable, and this is assumed to be true when the 
 disease is not inoculable. 
 
 This brief exposition suffices to show how numerous are the 
 possible applications of serumtherapy. There is hardly a disease 
 against which a serum cannot be prepared. Theoretically, the prob- 
 lems are easily solved while, as w*e shall see later, practical applica- 
 tions have not completely realized the hopes which were aroused by 
 laboratory researches. The more we study the question the greater 
 we find the difficulties to be overcome. 
 
 Various Organic Fluids Employed in Therapeutics. Therapeutic 
 action being dependent upon soluble substances, serum as well as 
 defibrinated blood may be used indifferently. As the latter product 
 is more difficult of manipulation, the former is generally resorted to. 
 
098 IMECTIOUS DISEASES. 
 
 Delbet, however, has thought it advantageous to utilize the total blood 
 just as it is obtained, when coagulation is prevented by means of an 
 oxalate which precipitates the calcium salts. Nothing is easier than 
 tin' preparation of serums. Two or three quarts (litres) of blood are 
 taken from the jugular of a horse. The clot that forms is very solid, 
 and the serum has a fine yellow amber color. It is kept in sterilized 
 small vials, containing a few drops of some antiseptic oil or a little 
 sublimated camphor. One of the inconveniences of the method is 
 that successive blood-letting, especially when repeated at short inter- 
 vals, often weakens the therapeutic action of the serum. This we 
 have shown to be true at least as regards the antistreptococcic serum, 
 and Marchoux has made the same observation. It has, therefore, 
 been believed that it was possible to replace the blood by a fluid 
 more easily procurable — milk, for example. The experiments of 
 Brieger, Ehrlich, and Ketscher have established that this fluid pos- 
 sesses therapeutic properties, but it is ten times less active than 
 serum, hence it cannot be used except when it is previously concen- 
 trated. 
 
 The curative fluid is generally introduced beneath the skin. Intra- 
 venous injection is employed only in laboratories. Introduction by 
 the digestive canal does not seem highly reliable. Ehrlich demon- 
 strated that the therapeutic substances present in the milk may 
 impregnate the organisms of the } r oung who ingest it, but this result 
 is observed only in nursing animals. In fact, Ketscher has shown 
 that the milk of goats immunized against cholera is curative when 
 injected beneath the skin, but produces no effect when it is ingested. 
 The active substance seems to be destroyed by the pepsin and pan- 
 creatic juice during digestion. When it is desired to introduce the 
 serum by the alimentary canal it should, according to the advice of 
 Dr. Chantemesse, be given in the form of enemata. 
 
 It is not necessary to dwell upon the rules of subcutaneous injec- 
 tions of serum. Except in certain special cases, the injection may 
 be made into any part of the body. When, however, considerable 
 quantities are to be introduced, it is advisable to operate upon the 
 abdominal region. Here the fluid is better tolerated and most rapidly 
 absorbed. The dose to be injected varies evidently according to the 
 gravity of the case and the activity of the serum. The former factor 
 can be appreciated by clinical observation alone; the latter may be 
 determined with accuracy. Hence, from the very beginning of his 
 researches, Behring endeavored to determine an exact measure for 
 
THERAPEUTICS OF INFECTIOUS DISEASE8. 699 
 
 the activity of serum. He firs! took ass unit the quantity oi scrum 
 
 which insured against the smallest fatal dose of the toxin. ll< 
 adopted, however, the method proposed by Ehrlich. Thu if prac- 
 tised in the following manner: The minimum fatal do e a regards 
 the guinea-pig is determined, and then an amount of toxins equiva- 
 lent to ten fatal doses is employed. This amount of toxin is called 
 by Behring the toxin unit. This unit is then mixed with serum, and 
 the whole is injected beneath the skin of guinea pigs. Normal anti- 
 toxin is of such strength that 0.1 c.cm. neutralizes the toxin unit 
 i. c, ten times the fatal dose Behring called an antitoxin unit the 
 amount of antitoxin contained in I c.cm., and, consequently, capable 
 of neutralizing ten toxin units or one hundred times the fatal dose. 
 When it is said that a serum has the value of ten units this means 
 that 1 c.cm. neutralizes one hundred toxin units or one thousand fatal 
 doses, or that the toxin unit is neutralized by 0.01 c.cm. A serum 
 presenting one hundred units is of such potency that 1 c.cm. neu- 
 tralizes one thousand toxin units or ten thousand fatal doses, and BO 
 on. This nomenclature is generally employed, except in the Pasteur 
 Institute, where the preventive power and not the antitoxic action 
 is determined. The animal which is to serve for the determination 
 receives the serum, and the following day the minimum fatal dose 
 is inoculated into it. The unit is the number of grams which 1 c.cm. 
 of serum is capable of protecting. If, for example, a guinea-pig 
 weighing 400 grams is preserved by 0.008 c.cm. of serum, 0.02 c.cm. 
 would be required for 1000 grams. Therefore, 1 c.cm. would preserve 
 50,000 grams of the animal. Hence, it is said that the serum has 
 the power of 50,000. Such is the unit of serum furnished by the 
 Pasteur Institute. This method is not without advantage, but it 
 presents a great inconvenience, for in employing the smallest fatal 
 dose one may, perchance, experiment upon an animal endowed with 
 a certain resistance, and attribute to the serum what is really due to 
 the particular state of the animal. This source of error is avoided 
 when the experiment is made with an amount of toxin ten times 
 larger than the minimum fatal dose. 
 
 The method of mixture is applicable not only to toxi-infectious 
 diseases, such as diphtheria and tetanus, but it may also be used to 
 determine the action of a serum upon a living culture. It is well to 
 note, however, that in the latter case the results are very different, 
 according as a mixture of serum and microbes is injected or according 
 as the serum and the culture are introduced at two different points 
 
700 IXFECTIO US DISEASES. 
 
 or successively at one and the same point. The curative action is 
 far more marked when the serum and microbes come in contact. 
 
 Various Applications of Serumtherapy. The works to which 
 the serumtherapy method has given rise are so numerous that it is 
 impossible to present here a complete summary of them. 1 The dis- 
 eases which may be treated by this method are divided into two 
 groups according as the pathogenic agent is or is not known and 
 cultivable. 
 
 The following is a list of infectious diseases for the treatment of 
 which serumtherapy has been practised: 
 
 Anthrax. Measles. 
 
 Cholera. Scarlatina. 
 
 Colon bacillosis. Staphylococcosis. 
 
 Diphtheria. Streptococcosis. 
 
 Leprosy. Syphilis. 
 
 Glanders. Tetanus. 
 
 Bubonic plague. Tuberculosis. 
 
 Pneumococcosis. Typhoid fever. 
 
 Proteobacillosis. Typhus fever. 
 
 Pyocyanobacillosis. Recurrent typhus. 
 
 Hydrophobia. Vaccinia and variola. 
 Rheumatism. 
 
 If we wish to make a complete study of serumtherapy we should 
 add the diseases peculiar to animals, such as symptomatic anthrax, 
 certain hemorrhagic septicemias, the disease of dogs, murr, and in- 
 toxications, notably poisonings by toxalbumins and venoms. 
 
 Cholera. Cholera has been the subject of important serum- 
 therapic experiments, and the results obtained, besides their theo- 
 retic interest, seem to be of such a character as to lead us to hope 
 that they will be applied to human therapeutics in the near future. 
 
 In 1892 Lazarus showed that a decigram of the serum of indi- 
 viduals cured of cholera is capable of protecting the guinea-pig 
 against an intraperitoneal inoculation of cholera vibrios. This 
 result, confirmed by various experimenters, was highly important. 
 It was objected, however, that the serum of normal men and animals 
 often possesses immunizing and curative properties. The result 
 being uncertain, it was necessary to investigate what occurs as a 
 result of vaccination. As early as 1890 Zasslein demonstrated 
 that, under these conditions, the serum acquires very marked 
 
 1 A complete description of serumtherapy and the principal bibliographical indications 
 may be found in the report which the author presented to the Congres franyais de 
 m^decine : Des applications des serums sanguins au traitement des maladies. Nancy, 
 August 6, 1896. Consult also: Landouzy, Les Serotherapies. Paris, 1898. 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 70] 
 
 germicidal properties, and, a few years later, Pawlowski and Buch- 
 stab, taking blood from vaccinated rabbits and guinea-pigs,* ucceeded 
 in conferring immunity upon animals of the same pecie l 
 results were confirmed by Pfeiffer and [ssaeff, and became the point 
 of departure for a scries of very Lmportanl research* rting 
 
 from the principle that the cholera toxin is contained in the vibrio* 
 and is not liberated until after the latter are disintegrated, Pfeiffer 
 was led to immunize animals by injecting into them culture* steril- 
 ized by heat or chloroform vapor or by inoculating into them pro- 
 gressive doses of living vibrios. By these procedures he succeeded 
 in obtaining- a serum of extraordinary efficiency, bul one which 
 does not act except against vibrionic peritonitis. It fails when it 
 is applied to animals inoculated by way of the intestine. The result 
 which, from a theoretical standpoint, was of considerable impor- 
 tance, did not lead to any practical application. Jt was, therefore, 
 necessary to take up the question under inspiration of the principles 
 which had guided Behring. This was done by his disciple Ramson. 
 In speaking of the mechanism of immunity, we have already referred 
 (p. 564) to the result obtained by this author with an antitoxic 
 serum quite different from the antibacterial serum obtained by 
 Pfeiffer. 
 
 Metchnikoff, Roux and Taurelli-Salimbeni have prepared a very 
 active antitoxic serum; 54 per cent, of the animals treated with this 
 fluid survived, and 16 per cent, of the controls. 
 
 These highly interesting results thus open the field for therapeutic 
 application. Of course, the phenomena are always more complex 
 in man, in whom we must take cognizance of microbic associations 
 which seem to play such a considerable role in the pathogenesis 
 of cholera. It must also be demonstrated that the serum obtained 
 by vaccinating an animal against one vibrio acts upon all varieties 
 of the colon bacillus. Even leaving aside the vibrios, which seem 
 to represent species or at least fixed races, like the bacillus of Finkler- 
 Prior and the avicidal vibrio of Gamaleia. it is known that, in 
 various cholera epidemics, quite different microbes have been found. 
 Such, for instance, are the bacilli of Massouah, Ghinda, and Ham- 
 bourg. On the other hand, Pfeiffer has shown that the serum of 
 an animal immunized against one variety of microbe does not act 
 upon the others. This fact is so constant that the author considers 
 it a means of diagnosticating different bacilli. It is true that these 
 results, which have not been completely confirmed by Sanarelli. 
 
702 INFECTIOUS DISEASES. 
 
 have been obtained in studying vibrional peritonitis and the serum 
 which acts upon the figurate element. The toxin is probably always 
 the same, and the antitoxic serum may succeed in all cases. This 
 question is worthy of study. 
 
 Even before the recent researches on antitoxins, a few attempts 
 were made upon man. During the epidemic of Hamburg, Freymouth 
 investigated the effects produced by the serum of convalescents. 
 Having learned that half a cubic centimetre injected into the peri- 
 toneum of a guinea-pig protects it against an inoculation of four- 
 fifths of a cubic centimetre of virulent culture, he practised injec- 
 tions upon three patients. The first one who had been attacked for 
 forty-eight hours received successively 10, 30, and 50 c.cm. a day. 
 The patient at first seemed to feel better, but on the fifth day he 
 grew worse, and death occurred on the sixth day. The second 
 patient recovered after an injection of 30 c.cm. on the third day. 
 On the sixth day, however, he still had vomiting and rhiziform 
 diarrhea. The third case was that of a woman suffering from a 
 slight attack. Her symptoms rapidly improved after an injection 
 of 20 c.cm. These observations are too few in number to warrant 
 a conclusion. At any rate, the method which consists in injecting 
 the blood of convalescents cannot have a great future. Anticholeric 
 serum must have an animal origin, and recent experiments with 
 choleric antitoxins seem to have greatly advanced the question. 
 The experimental study is nearly completed; clinical observation 
 must decide the problem. 
 
 Colon Bacillus. As the colon bacillus constantly secretes toxic 
 substances in the intestine, it is plain that a series of reactionary 
 phenomena terminating in the production of antitoxins must occur 
 within the organism. This is precisely what takes place. The serum 
 of normal individuals may neutralize doses of B. coli ten times 
 larger than those which are usually fatal. Thus we recognize a 
 first spontaneous effort toward immunization. It suggested the 
 next step, which consists in increasing the resistance of the organism 
 by the usual procedures. Cesaris, Demel and Orlandi, Salvati and 
 Gaetano demonstrated that the soluble products of the colon 
 bacillus are capable of conferring immunity upon animals and 
 imparting therapeutic characters to their sera. 
 
 Drs. Albarran and Mosny, having vaccinated animals by alter- 
 native injections of filtrates of the organs of animals dead from 
 colon bacillosis and of living cultures, obtained a serum which, in 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 70:; 
 
 doses of 0.(). r > c.cm., immunized the guinea pig again I a srirulenl 
 inoculation practised twenty-four hours later; 0.25 c.cm. sufficed 
 to protect against an amounl twenty time larger than the fatal 
 dose. By studying the serum according to the method of mixture, 
 it may be seen that one drop neutralizes the fatal dose. Finally, 
 2 c.cm. injected two hours after inoculation of an amount of culture 
 equal to double the fatal dose saved the animal 1. 
 
 These results are sufficiently encouraging to warrant practical 
 applications, notably in urinary infections, which Drs. AJbarran and 
 Mosny had particularly in view. It is more difficult to employ the 
 serum under other circumstances, since it is nol alway possible to 
 determine during the life of animals whether the symptoms are due 
 to the colon bacillus or not. The serum cannot, therefore, be utilized 
 except in certain surgical cases. 
 
 The close analogy existing between the colon bacillus and the 
 bacillus of Eberth have led some experimenters to invest ig:it e whether 
 the serum which antagonizes colon bacillary infection can likewise 
 combat typhoid fever. Sanarelli demonstrated the mutual immuni- 
 zation by the two bacilli. C. Dcmel and Orlandi recognized that the 
 serum of animals vaccinated against the colon bacillus prevents 
 experimental typhoid infection. They have even made attempt- on 
 man and obtained improvement by treating typhoid cases with this 
 serum. 
 
 In spite of their interest, these results should not be considered 
 as proving that the anticolon bacillus serum is the specific of typhoid 
 fever. Loeffler and Abel proved that, although the anticolon bacillus 
 serum acts upon typhoid infection and the antityphoid serum 
 upon colon bacillus infection, each of the sera is especially active 
 when employed in the treatment of the disease against which the 
 animal furnishing the serum has been previously protected. Here 
 is a question of specificity which, while not absolute, is nevertheless 
 undeniable. 
 
 Diphtheria. The employment of antidiphtheritic serum has com- 
 pletely transformed the prognosis of diphtheria. All statistics 
 clearly establish that, under the influence of the new medication, 
 the death-rate has diminished in extraordinary proportions and the 
 period of convalescence considerably reduced. Moreover, the rapid 
 evolution of the disease has enabled the physician to abandon 
 tracheotomy and to substitute intubation for this operation. It 
 would be right to devote the greatest part of this chapter to the 
 
704 INFECTIOUS DISEASES. 
 
 study of the antidiphtheritic serum. The question is so well known 
 to-day, however, that we shall be contented with a summary of the 
 most important facts. 
 
 Science is indebted to Behring for the two discoveries which led 
 to the preparation of the serum. He demonstrated the certain 
 means of immunizing animals against diphtheria, and he subse- 
 quently recognized that then' sera became antitoxic. On this latter 
 discovery antidiphtheritic serumtherapy is founded. In human 
 therapeutics he employed the serum of sheep immunized by means 
 of toxins attenuated by trichloride of iodine. Aronson used the 
 serum of dogs. He later employed the serum of the horse. Roux 
 and Martin also resorted to the horse. They added to the toxin 
 one-tenth of its volume of Gram's fluid, which contains 1 gram 
 of iodine, 3 grams of potassium iodide, and 100 grams of water. 
 One-fourth of a cubic centimetre of the mixture is first injected, 
 and the dose is progressively increased. It is thus possible at the 
 end of three months of treatment to reach a dose of 250 c.cm. of 
 the filtered culture. 
 
 The first therapeutic applications to the human subject were made 
 in 1892 in the wards of Dr. Henoch, in Berlin. They were not very 
 encouraging. Two years later, however, a new series of contributions 
 appeared which determined conclusively the value of the serum. 
 Ehrlich, Kossel, and Wassermann first reported the results of 233 
 inoculations practised upon children. The death-rate was 23 per 
 cent. In a great number of cases the serum employed was not very 
 active. Truly efficacious serum had been used only in 92 cases, and 
 the death-rate had fallen to 12 per cent. About the same time 
 Korte presented statistics of 121 cases. The death-rate was 33 per 
 cent., while previous to the use of the serum it was 45 per cent. 
 The figures of Aronson are far better. With his antitoxin he had a 
 death-rate of 12 per cent, in a total of 255 diphtheritic children. 
 
 It would be superfluous to recall other less important statistics 1 
 published in Germany about the same period, indicating a notable 
 decrease in the death-rate. The results obtained in France are by 
 no means less favorable. In a very remarkable thesis Bayeux 2 
 
 1 For all statistics and bibliographical data relative to this first period, consult the 
 article of L6pine: La se>otherapie de la diphterie. Semaine m^dicale, 1894, p. 573. 
 See also the report presented by Haushalter in the Congres de Nancy, August, 1896. 
 
 2 Bayeux. La diphtdrie depuis Aret§e le Cappodocien. R^sultats statistiques de 
 230,000 cas. Thfee de Paris, 1899. 
 
THERAPEUTICS OF INFECTIOUS DI8EASE8. 70.", 
 
 tabulated all the statistics and reached the conclu ion thai prior 
 to serumtherapy the death-rate in diphtheria was 56 per cent. 
 and bad fallen to L6 per cent, after the introduction of this 
 method. 
 
 II, is at present generally agreed thai u 'ruin having 100 unit- 
 is a very efficacious one, viz., thai I c.cm. is sufficienl to aeutralize 
 loo toxic units, that is, looo fatal doses. Such is the strength of 
 the serum furnished by the [nstitul Pasteur. 'I'd'' Belgian serum, 
 prepared under the direction "I' Punch in the laboratory of 
 Leopold Park, has a power of '200. In Germany the laboratory 
 of Meister, Lucius, and Urihiing,in Hoechst, furnishes tin-'''- varieties 
 of sera in vials of 10 c.cm. stamped by Hi' 1 government. Scrum 
 No. 1 has a power of (io units per c.cm.; No. 2 is equivalenl to 
 100 units, and No. 3 to 150. The ('(intents of one vial, Bay 10 c.cm., 
 is generally injected, and one of these three varieties is employed 
 according to certain more or less clearly determined condition-. On 
 the one hand, the dose is proportioned to the age and weight of (In- 
 patient; on the other hand, serum No. I is made use of if the case 
 is of moderate gravity and treated from the beginning. If the 
 larynx is involved and if three or four days have already elapsed, 
 then serum No. 2 is resorted to. No. 3 is used in cases of extreme 
 gravity. In France, where one serum only is employed, the dose 
 is diminished or increased according to the same indications 
 described with reference to the German method. 
 
 In order to appreciate the method it is necessary to take into 
 account a number of factors depending upon the patient. In the 
 first place, the age of the subject. In children diphtheria is always 
 more serious than in adults, and it is the more dangerous the younger 
 the child. From this point of view the latest German statis 
 are altogether convincing. The death-rate is still as high as 41^ 
 per cent, in children under one year of age. From one to two years 
 of age it is 36.6 per cent. From two to five years it varies from 
 15 to 18 per cent. It is from 5 to 10 per cent, in children between 
 five and fifteen years of age. It then falls to 2.7 per cent, from 
 fifteen to twenty years of age. and to 0.8 per cent, from twenty 
 to thirtj r years of age. The best results are observed at this last- 
 named epoch of life. Beyond thirty years of age diphtheria is of rarer 
 occurrence, but it is graver. The death-rate reaches 3.7 per cent, 
 between thirty and forty years of age, and to 9.1 per cent, after 
 fifty years of age. 
 
 45 
 
706 INFECTIOUS DISEASES. 
 
 Although the mortality remains high in children, it is among 
 them that serumtherapy renders the most valuable service. In 
 fact, adults recover quite often, no matter what the treatment 
 employed; while children succumb because of their weak resistance 
 to the toxin and on account of the extension of the process into the 
 larynx. Hence, the death-rate is relatively less affected with refer- 
 ence to adults. It is reduced, especially in children, and notably 
 in those suffering from croup. There is, however, an indispensable 
 condition for success, that is, intervention as earl)'' as possible. On 
 this point all clinical observers are in accord. In this connection 
 the figures of the German statistics are highly suggestive. The 
 death-rate is 5.4 per 100 when the treatment is begun on the 
 first day, and 6.7 per cent, when it is instituted on the second day. 
 It rises to 10 per cent, for the third day and to 23 per cent, for 
 the fifth day. Prompt intervention has the double advantage of 
 combating the disease while the intoxication is as yet unpronounced 
 and secondary infections have not assumed a dangerous character, 
 and by neutralizing the toxin early certain incidents of convales- 
 cence, such as paralysis are, perhaps, prevented. 
 
 In order to benefit the patient as promptly as possible by the 
 effects of the serum, most bacteriologists advise an injection as 
 soon as there is the slightest doubt as to the nature of a sore throat, 
 or even as soon as any exudate whatever is present. At the same 
 time a culture is prepared from the exudate, and, at the end of 
 twelve to fifteen hours, the bacteriological diagnosis indicates the 
 nature of the disease. The conduct of the physician is thus decidedly 
 simplified. These principles, however, cannot be accepted without 
 some reservation. Here we touch a delicate point which has already 
 given rise to much controversy. For my part, I believe that physi- 
 cians neglect too much the examination of the patients in the 
 belief that they are able to establish a diagnosis, prognosis, and 
 therapeutic indications by means of the data furnished by bacteri- 
 ology. It seems to me that the diagnosis of diphtheria is not as 
 difficult as it is said to be. In our isolation wards, where we receive 
 all cases of anginas attended by the slightest whitish exudate, our 
 pupils are accustomed to make the differential diagnosis. A diag- 
 nostic mistake occurred only in those cases of benign anginas which 
 were cured almost without any treatment after cleansing of the throat. 
 Two varieties of cases are observed in adults : The angina may 
 present the indisputable characteristics of diphtheria. The serum 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 707 
 
 is then i i ij ecte< I forthwith, and :i culture prepared. In other cs e 
 fche wore throat has the aspect of an herpetic angina. A culture mu t 
 be made, and if on the following day Loeffler's bacillui i found, 
 an injection may be made if necessary. Such ha been our practise 
 in our wards reserved Tor adults. In the case of children more 
 prompt notion is required. In fact, it is ;ii thai epoch of life thai 
 diphtheria is a grave disease. The com:-'' of the procet musl be 
 arrested from the beginning and involvement of the larynx pre- 
 vented. From this standpoint there is a radical difference between 
 diphtheria of children and that <>1 adults. In adults, diphtheria 
 is a relatively benign malady which seldom kills of itself and which 
 is particularly dangerous because of renal complications and con- 
 secutive paralysis. Such is not the case with children. II 
 soon as there is the slightest doubt, serum injections must be re- 
 sorted to. The few inconveniences of the serumtherapy method, 
 the accidents which it may produce, and which will be referred to 
 in the following chapter, are nothing in the presence of the urgency 
 for prompt action. To wait for the result of the cultures would be 
 to lose valuable time, the more valuable as it occasionally happens 
 that no colony develops at the end of twelve or even twenty-four 
 hours. In brief, in the case of a child presenting the clinical signs 
 of diphtheritic angina, and especially of croup, serumtherapy 
 must be applied immediately. In cases of pseudomembranous 
 angina presenting the characters of herpetic sore throat clinically 
 not resembling diphtheria, it is usually permissible to wait for the 
 result of cultivation, and, when one has a certain amount of experi- 
 ence in diphtheria, bacteriological examination will confirm the data 
 of observation. In order to comprehend the action of the serum 
 we must study successively the modifications which occur in the 
 local and general state of the patient. Locally, the serum cai - - 
 exfoliation of the pseudomembrane. Very often the aspect is 
 completely changed at the end of twenty-four hours. The exudates 
 are softened, deliquescent, and the throat begins to be relieved of 
 congestion. It is well to remember, however, that on the day 
 following the injection an increase in the extent of the pseudo- 
 membrane may occur, for the reason that the parts were already 
 invaded by the bacillus, and the exudate was produced in spite of 
 the action of the serum. Coincident \y, the engorgement of the 
 lymphatic glands diminishes. Four or five days are generally required 
 for the complete disappearance of the exudates. They sometimes 
 
708 INFECTIO US DISEASES. 
 
 persist for a longer period, for a week or more; but they are then 
 less extensive, occupying only a part of the tonsils, and the state 
 of the patient causes no anxiety. While the local lesions subside, 
 the general state improves. The patients experience a feeling of 
 exhilaration, and the} 7 feel that the disease is checked. In conse- 
 quence of the injection a profuse perspiration often occurs, which is 
 a happy phenomenon, since it seems that sweating eliminates the 
 toxin. The influence upon the temperature is variable. The serum 
 frequently produces a transitory febrile movement, and if fever 
 existed it falls at the end of twenty-four hours, while at the same 
 time the frequency of the pulse diminishes. 
 
 If the case is one of laryngeal diphtheria the result is more re- 
 markable b} T curtailing the duration of the evolution and favoring 
 elimination of the pseudomembranes. Serumtherapy has left no 
 longer any occasion for tracheotomy. The method of intubation 
 has been resumed. This change in operative procedures has several 
 advantages. Tracheotomy is not only dangerous, but by opening 
 the trachea it permits the penetration of external germs or of 
 microbes present in the wound, and thus favors the development 
 of bronchopneumonia. Besides these immediate accidents, it may 
 give rise to some remote ones. According to Landouzy, a great 
 number of tracheotomized patients die at a later period in conse- 
 quence of the development of pulmonary tuberculosis. 
 
 While there is universal agreement as to the facts above reported, 
 doubt arises when we consider the role of the serum with respect 
 to certain complications or grave manifestations, such as albumin- 
 uria. This question requires new investigation. At present it is 
 impossible to form an opinion in view of all sorts of contradictory 
 assertions. Some authorities contend that the serum prevents or 
 diminishes diphtheritic albuminuria. Others, taking ground upon 
 some experiments, assert that the serum gives rise to renal alter- 
 ations. All that is possible to state is that albuminuria does not 
 constitute a contraindication to serumtherapy. On the contrary, 
 diphtheritic albuminuria, indicating a profound intoxication of the 
 organism, demands active intervention. The serum cannot, of course, 
 overcome pre-existing renal lesions. The important fact to observe 
 is that serumtherapy does not aggravate it. Clinical facts are far too 
 complex to permit a decisive opinion. The question should be taken 
 up experimentally to determine whether antidiphtheritic serum gives 
 rise to renal lesions or aggravates pre-existing alterations in animals . 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 709 
 
 As to paralyses, I hey are s1 ill quite frequenl . hi hoped, I 
 thai- when serumtherapy is promptly applied while the toxins are 
 not yet abundant and the nervou i elements are more re i tant, the 
 accidents will diminish. 
 
 Wo have thus far endeavored to sum up the advants 
 diphtheritic serum, disregarding the accidents which may be attrib 
 utod to its use and which will be Btudied later on. We have ihown 
 what should bo the lino of oondud a regards the opportune 
 Injection. The question of concomitanl treatmenl now remaini to 
 be considered. 
 
 It has been asserted that antiseptic lavage of tho Ihroal hin 
 the action of the serum, and many physicians al presenl op 
 forcible removal of pseudomembranes. If seems to me thai one 
 should not have any preconceived ideas on these questions, h is 
 better to be guided by observation of each patient. All that can 
 be said is thai in the treatmenl of diphtheritic anginas of adults 
 we have obtained excellent results by means of lavage with boiled 
 water, with solutions of carbolic acid and thymol, or cleansing with 
 lemon juice. Finally, in certain cases we have noticed that con- 
 comitant injections of pilocarpine manifestly favor the action of 
 the serum. The injections, which have been so fiercely opposed, 
 seem to produce favorable results, provided the state of the heart 
 and of the kidneys be carefully watched. When the heart is strong 
 and the urine is not albuminous, the injection of one centigram of 
 nitrate of pilocarpine rapidly ameliorates the general state and 
 favors detachment of the pseudomembranes. In the case of adults 
 it is a good auxiliary to serumtherapy, at least in certain instanc 
 
 Leprosy, Glanders. A few serumtherapy attempts were made by 
 Garrasquilla against leprosy. The serum caused the return of sensi- 
 bility, and the disappearance of the spots, edema and tubercles, and 
 cicatrization of ulcerations, etc. 
 
 Few researches have been pursued on the serumtherapy of glan- 
 ders. We have no others to cite except those of Chenot and Picq, 
 who, out of ten inoculated animals, cured seven by injecting into 
 them the serum of cattle, that is, a species naturally refractory to 
 the disease. 
 
 Bubonic Plague. Yersin, Calmette, and Borrea succeeded in 
 immunizing animals against bubonic plague by means of repeated 
 inoculations of cultures heated for an hour at a temperature of 
 136.4° F. (5S° C). Dr. Roux has likewise immunized horses with 
 
710 IXFECTIO US DISEASES. 
 
 toxins. The serum thus obtained gave good results in inoculated 
 monkeys (Wyssokowitz). In man it confers an immunity which 
 lasts for about a fortnight. The therapeutic attempts made by 
 Yersin in India reduced the death-rate from 80 to 49 per cent. 
 In China, out of twenty-six sufferers treated in 1897, only two 
 deaths occurred. 
 
 Pneumococcosis. The study of antipneumococcic serumtherapy 
 has given rise to a great number of researches, of which Dr. Mosny 
 speaks in a review. 1 As this author remarks, animals may be 
 immunized by several procedures : One, accidentally discovered by 
 A. Fraenkel, and systematically employed by some experimenters, 
 consists in injecting dilutions of virulent microbes. It seems that, 
 in order to succeed, it is necessary to employ cultures of moderate 
 strength, for, according to Foa and Scabia, the highly virulent 
 agents kill the animals or produce no effect at all — i. e., do not 
 immunize them. The attenuated cultures gave satisfactory results 
 in the hands of Netter, Emmerich, Fowitzky, Foa, and Scabia. 
 
 Cultures sterilized by filtration or by the addition of a little 
 chloroform are generally employed, but they must be heated to 
 140° to 149° F. (60° to 65° C). Without this precaution the fluid 
 is highly toxic and seldom immunizing. As in the case of diphtheria, 
 the toxin may also be modified by means of the iodo-iodide reagent ; 
 an immunity persisting for three months is thus obtained (Foa and 
 Carbone). Finally, for securing good results it is necessary to 
 immunize by means of microbes possessing about the same virulence 
 as those against which the animals are to be protected. It is like- 
 wise possible to immunize animals by means of filtered macerations 
 of the organs of rabbits dead from pneumococcic septicemia (Mosny), 
 by means of sterilized sputa or exudates, the blood serum or the 
 serum produced by vesicatories (Klemperer). Whatever the mode 
 of vaccination, the serum of animals that have been rendered 
 refractory becomes immunizing and conservative. 
 
 Pneumococcic diseases being often benign in man, a serum of mod- 
 erate activity may render great therapeutic services. It hastens 
 recovery toward which the natural forces of the organism tend. 
 
 G. and F. Klemperer undertook the first practical applications. 
 After injecting themselves with from 0.5 c.cg. to 3 c.cg. of serum of 
 immunized rabbits, and thus proving the innocuity of the fluid, they 
 
 1 Mosny. La vaccination et la gu6rison de Pinfection pneumococcique exp6rimentale 
 et de la pneumonie franche de l'konxme. Arch, de m£d. exp6r., 1893, p. 259. 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 711 
 
 injected from r> c.cm. to LO c.cm. into patient offering from typhoid 
 fever. The result was negative. They then operated upon six pneu- 
 monia patients, and with from I c.cm. to 6 c.cm. of serum obtained 
 a fall in the temperature, [n two cases the di ea ewa immediately 
 arrested, [n another scries of twelve ca e G. Klemperer liki 
 observed very pronounced amelioration with doses varying from 
 5 c.cm. to LO c.cm. Facts subsequently published by Foa and Car- 
 bone, Foa and Scabia, and Janson are no less encouraging. By tabu- 
 lating the observations of these various authors the writer fincle a 
 total of thirty-nine cases. In only one case (an observation of Janson 
 the result was nil. In all the other cases there was very marked 
 improvement. In twenty-one cases the crisis was produced on the 
 following day or two days after intervention/ and in several casee on 
 the sixth, fifth, and even the fourth day. In view of such data it 
 is difficult not to admit the favorable action of the serum. 
 
 Not only the serum of rabbits but also that of man may serve for 
 therapeutic purposes. In some unpublished experiments, the results 
 of which were indicated in a memoire of Prof. Bouchard, we recog- 
 nized with Dr. Charrin that "the injection into rabbits of blood 
 serum obtained by venesection from a man suffering from pneumonia 
 in the stage of defervescence or seven days after, renders these ani- 
 mals refractory to inoculation with pneumococcus, and this four days 
 and even eleven days after the injection of the serum." 1 Andeoud 2 
 applied these experimental results to man. He injected into two 
 patients the serum drawn from a pneumonia convalescent. In one 
 of the cases two injections sufficed to bring about a crisis on the 
 sixth day. In the other instance the disease terminated on the fifth 
 day, fifteen hours after the first injection. In a communication 
 addressed to the Congress of Rome, Maragliano announced that he 
 had obtained thirty-nine favorable results by the employment of the 
 serum of immunized animals or of cured patients. In attempts of 
 this kind, however, the serum of the dog should never be resorted 
 to. This serum, far from preventing the infection of the rabbit, 
 favors it. An observation of Foa and Scabia proves that it acts in 
 the same manner upon man. An injection of 2 c.cm. or 3 c.cm. of 
 the serum of a dog which had previously received virulent cultures 
 
 1 Bouchard. Sur les pretendues vaccinations par le sang. Revue de m^decine, 
 January, 1892, p. 15. 
 
 2 Andeoud. Serotherapie dans la pneumonic. Revue med. de la Suisse romande, 
 February. 1893. 
 
7 1 2 INFECTIO US DISEASES. 
 
 of pneumococci, caused a notable aggravation of the general phe- 
 nomena, an increase in the fever, and a manifest delay in recovery. 
 
 Although pneumonia is a disease which, in the majority of cases, 
 naturally terminates in recovery, there are other pneumococcic mani- 
 festations which almost invariably cause death. Meningitis is among 
 the number. Here is a subject for investigation which is of great 
 importance and necessarj 7 for a final judgment of the value of serums. 
 In fact, there is already a recorded observation which, although 
 unique, is none the less encouraging. Righi 1 observed a seven-year- 
 old child presenting the typical symptoms of acute meningitis. 
 Examination of the blood revealed the presence of the pneumococcus. 
 On the fifth day the author injected 1 c.cm. of serum taken from a 
 convalescent of pneumococcic meningitis. The symptoms improved 
 and the patient recovered on the eighth day. The serum injected 
 was endowed with energetic germicidal properties and proved to be 
 preservative and curative for mice and rabbits. 
 
 Proteobacillosis. It has long been known that it is possible to 
 immunize against the proteus with soluble substances or even well- 
 defined products like neuridin. De Nittis 2 has made known a mode 
 of immunization by means of living cultures and succeeded in obtain- 
 ing an active serum. He showed that the guinea-pig could endure 
 an intraperitoneal injection of from 3 c.cm. to 3.5 c.cm. of a culture 
 1.5 c.cm. to 2 c.cm. of which, when introduced by the veins, killed 
 rabbits weighing 2 kilograms within twenty-four hours. The serum 
 of guinea-pigs thus treated proved to be very efficacious. A dose of 
 2 c.cm. per kilogram of animal suffices to protect rabbits against 
 inoculations which kill the controls in twenty-four hours. 
 
 Pyocyanobacillosis. Pyocyanobacillosis or pyocyanic disease has 
 been the subject of important serumtherapic investigations. The 
 experiments pursued by Bouchard 3 led this scientist to formulate 
 certain conclusions, several of which were then absolutely new, and 
 which, from the standpoint of general pathology, are of such 
 importance that it will be interesting to give a resume of them here. 
 
 After determining that the blood of naturally immune animals has 
 but a slight therapeutic action, and that, in order to obtain an effi- 
 cient serum, it is necessary to employ the blood of immunized animals, 
 
 1 Pdghi. La sieroterapia nella meningite. La riforma medica, 1894, iii. p. 566. 
 
 2 De Nittis. Serotherapie du Proteus vulgaris. Societe de biologie, June 13, 1896. 
 
 3 Bouchard. Les pretendues vaccinations par le sang. Revue de medecine, January, 
 1892. 
 
THERAPEUTICS OF INFECTIOUS DISEA8E8. 71.', 
 
 Bouchard demonstrated that the serum i a actives , and even more 
 energetic than, defibrinated blood, tn order to prove thai the ei 
 were due to the serum, viz., to soluble matter andnol to morpho- 
 logical elements, this author filtered the fluids through porcelain. 
 The results were not modified. I [e then I udied the urine of animals 
 which had received blood of immunized animals and found thai it 
 did not confer immunity. It did nol acl otherwise than the urine 
 of animals into which sterilized cultures had been injected. More- 
 over, he showed that the immunity conferred by the -••nun 
 short duration. If it existed on the eighteenth day il disappeared 
 on the twenty-second. The serum exerts an immediate protective 
 action which gradually diminishes, while the bacterial substanc 
 first weaken the resistance and subsequently increase it. Hence it 
 may be concluded thai the active substance of the serum is rapidly 
 destroyed within the organism of the animal into which the injection 
 has been made, and that the immunity produced by the serum is due 
 not to a reaction of the organism, but simply to the introduction of 
 some germicidal substance. Finally, a last distinction must be es1 ab- 
 lished between the immunizing substances of cultures and th< 
 the serum. The former resists a temperature of 239° F. (115 * I 
 the latter are destroyed between 140° F. and 149° F. (60° C. and 
 65° C), and at the same time the germicidal action disappear.-. 
 
 Staphylococcosis. The first experimental attempt of serumtherapy 
 was directed against the staphylococcus. Hericourt and Richet, in 
 a study on the staphylococcus pyosepticus, which is a variety of the 
 staphylococcus alhus, recognized that infection in a rabbit could be 
 prevented by injecting the blood of dogs. The result was especially 
 manifest when use was made of dogs that had recovered from a 
 previous inoculation of staphylococci. 
 
 The method, which consists in employing the serum of animals 
 cured from a virulent inoculation, is too uncertain for generalization. 
 It was, therefore, necessary to immunize by the usual procedures, 
 notably with sterilized cultures. Drs. Rodet and Courmont discov- 
 ered the interesting fact that the soluble products of staphylococci. 
 far from increasing the resistance, diminished it and predisposed the 
 organism to infection. By continuing their researches, however, they 
 succeeded, by means of alcohol, in extracting a substance capable of 
 conferring upon animals a sufficiently marked immunity. Dr. Cour- 
 mont subsequently learned that the serum of animals thus prepared 
 has no germicidal power, but possesses the property of attenuating 
 
714 INFECTIOUS DISEASES. 
 
 microbes and causing them to lose their virulence. The practical 
 importance of this result is evident. 
 
 It is not only by employing substances soluble in alcohol that 
 animals may be immunized. Yiquerat arrived at the same result by 
 a procedure first employed by Behring. Viquerat injected a 1 : 2000 
 solution of trichloride of iodine into the neighborhood or the 
 interior of a staphylococcic abscess. Under the influence of this 
 treatment the abscess was rapidly cured, and its contents were trans- 
 formed into a serum which was filtered in order to free it from 
 microbes which it might contain. This fluid, like the blood serum 
 of cured individuals, possesses preventive properties against the 
 intravenous inoculation of staphylococci in rabbits. Having thus 
 obtained a serum of a preventive power of ttfoU; the author in- 
 jected from 10 c.cm. to 65 c.cm. of it into various patients, and 
 obtained a speedy cure of furuncles, paronychia, and even osteomye- 
 litis. He next immunized animals by means of cultures to which 
 trichloride of iodine was added, and obtained from goats a serum 
 endowed with a power of from 10,000 to 500,000. When injected 
 into patients this serum caused a very intense reaction at the point 
 of the lesion. At the end of fifteen or twenty hours the phenomena 
 improved and notable amelioration resulted. Finally, Kose immun- 
 ized a goat by first injecting it with cultures attenuated by heat, then 
 more and more virulent fluids. The serum of this animal, although 
 devoid of all germicidal action, increased the resistance of inoculated 
 rabbits, but did not save them ; they died less rapidly, however, than 
 the controls. It is true that the goat was insufficiently immunized. 
 
 Streptococcosis. The history of antistreptococcic serumtherapy has 
 been presented in such a faulty way, except in Bonnet's 1 work, that 
 we think it worth while to re-establish the succession of investiga- 
 tions by indicating the dates. 
 
 In order to prepare an efficient serum it is always necessary to 
 reinforce the immunity of the animals. Several procedures were used 
 with quite variable results. We may group the attempts in the 
 following manner : 
 
 1. Immunization by Living Cultures. Lingelsheim, 2 who employed 
 all cultures heated to 145.4° F. (63° C.) for an hour, obtained only 
 
 1 Bonnet. La serumtherapie dans les affections streptococciques. Gazette hebdoma- 
 daire, 1895, p. 229. 
 
 2 Lingelsheim. Exp. Untersuchungen uber morpholog, cultur, und patholog. Eigen- 
 schaften verschiedener Streptokokken. Zeitschr. f. Hygiene, Bd. x., Heft 2, 1891. 
 
THEEAPEUTIOS OF INFECTIOUS DISEASES. 71fi 
 
 negative results. Willi cultures attenuated according to Behring't 
 procedure, viz., by means <>r trichloride of iodine, he succeeded in 
 immunizing only two mice out of twelve. By operating upon rabbits, 
 De P.'iolis 1 rendered the animals refractory by injecting into their 
 veins non-virulent cultures. We succeeded in conferring immunity 
 
 upon .'uiini.'i.ls by making successive inoculations of virulent cultures 
 
 beneath the skin of their ears. The reactions were le and less 
 intense and finally became so mild ;is to give rise only to circum- 
 scribed abscesses. 2 
 
 2. Immunization by Sterilized Cultures. As in other infectii 
 immunity from streptococcic infection may be conferred by means 
 of soluble products. A little difficulty is encountered here. Sterilized 
 cultures contain two groups of substances with antagonistic action. 
 Some of them diminish resistance. Others increase it. If from 
 5 c.cm. to 12 c.cm. of :i culture filtered through porcelain be injected 
 into animals, subsequent inoculation of the living microbe produces 
 death far more rapidly than when no previous intervention had 
 taken place 
 
 In one case we saw an animal thus succumb eleven times more 
 rapidly than the control. It is to be noted that no relationship 
 exists between the quantity of the toxic substance injected and the 
 degree of predisposition created by its injection. If, however, cultures 
 sterilized by heat are employed, the effects are quite different. Rab- 
 bits which received from 5 c.cm. to 30 c.cm. of the fluid thus obtained, 
 and which were inoculated from four to thirty days later, survived 
 while the controls died within a few days. 3 
 
 We must remark, however, that these results are perhaps appli- 
 cable only to rabbits or at least to certain animal species. There are 
 others in which injections of filtered cultures seem to increase the 
 resistance. Such is the case with the horse. On the other hand, the 
 emplojanent of cultures sterilized by heat is not without danger. 
 Very virulent cultures, or even cultures of moderate activity in which 
 certain varieties of streptococci are developed, contain noxious sub- 
 stances which cannot be destroyed by heat. Under these conditions 
 their injection gives rise to emaciation, at times cachexia and death, 
 
 1 De Paolis. Sulla proprieta vaceinale dello streptococco dell' erisipela. La riforma 
 niedica, 1SS9, No. 200. 
 
 2 Roger. Modifications du serum & la suite de l'erysipele. Society de biologie, 
 October 25, 1S90. 
 
 8 Roger. Action des produits solubles du streptocoque de l'erysipele. Society de 
 biologie, July 4, 1S91. 
 
716 INFECTIO US DISEASES. 
 
 and may fail to confer immunity. These remarks account for a 
 great many contradictory facts. 
 
 3. Immunization by Mixed Procedures. Mironoff 1 obtained good 
 results by combining the proceedings hitherto described. He em- 
 ployed successively, in the same animal, attenuated cultures and 
 virulent cultures in progressively increasing doses. He thus suc- 
 ceeded in rendering animals able to bear, without reaction, quan- 
 tities of virulent cultures ten times larger than those which are fatal 
 for the non-immunized. 
 
 Whatever the method employed for immunizing animals, the 
 serum of the vaccinated acquires therapeutic properties. This was 
 proved by the author's experiments 2 and by those of Mironoff. 3 Ac- 
 cording to this author the action of the serum is proportionate to the 
 dose employed; but it does not affect the local lesions. As the result 
 of extremely remarkable researches, Marmorek 4 succeeded in pre- 
 paring a serum by means of cultures of incredible virulence. To kill 
 a rabbit a dose of 0.000,000,000,01 c.cm. of the culture is sufficient. 
 The rabbits into which the serum is injected a few hours before the 
 inoculation resist this microbe. Those that are first inoculated and 
 then treated a few hours later also survive. Finally, Parascandolo 
 immunized animals against the staphylococcus and streptococcus. 
 He employed highly virulent microbes which he cultivated in bouil- 
 lon containing sugar. The cultures sterilized by the addition of 5 per 
 cent, of phenol were injected into dogs, rabbits, and guinea-pigs in 
 progressively increasing doses. The serum of animals thus prepared 
 neutralizes in vitro the toxins and the microbes; its action proved 
 preventive and curative in animals into which these pyogenic mi- 
 crobes were inoculated and had caused either a generalized infec- 
 tious process, such as puerperal fever or septicemias, or a localized 
 process like erysipelas. 
 
 What renders these investigations interesting is the fact that this 
 author succeeded in cultivating several pyogenic microbes in the 
 same medium, and thus obtained a serum which was efficacious 
 against species that are often found associated. 
 
 1 Mironoff. Immunisation des lapins contre le streptocoque. Arch, de medecine 
 exper., 1893, p. 441. 
 
 2 Roger. Contribution a Petude experimentale du streptocoque de Perysipele. Revue 
 de medecine, 1892, p. 953. 
 
 8 Mironoff. Loc. cit., 1893. 
 
 * Marmorek. Sur le streptocoque. Societe de biologie, February 23, 1895. Strep- 
 tocoque et serum antistreptococcique. Annales de l'Institut Pasteur, July, 1895, p. 593. 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 717 
 
 Thus a number of experimenters arrived independently at identical 
 
 conclusions, viz., possibility of vaccinating animal against the 
 streptococcus; possibility of preparing a scrum efficacious against 
 experimental streptococcic infections. 
 
 Hence, it w;ls natural to attempt Hie treatment by antistri 
 coccic serum in human diseases. The first endeavor wb ma 
 Gramakowsky, who treated two cases of erysipelas. The result 
 not very encouraging, since (me of the patient died. On February 
 
 23, 1X95, wo reported to llie Kiological Society two successes ob- 
 tained in the wards of I )r. ( 'liniiin. 1 They were two women suffering 
 from puerperal fever, one of them profoundly infected, Both 
 survived. The following month we reported two other cases, and 
 on the same day Dr. Marmorek 2 announced that he hud successfully 
 treated forty-six patients suffering from erysipelas. From this 
 moment on contributions succeeded each other in Franco as well 
 as in other countries. The results were quite variable and i 
 rise to a good deal of discussion. 
 
 In order to practise serumtherapy on man it has been necessary 
 to resort to animals capable of furnishing great amounts of blood. 
 Hence, the horse was chosen. 
 
 Following the suggestions drawn from our investigations upon 
 rodents, we immunized animals by means of streptococcic cultures 
 sterilized by heat. It is likewise possible to confer immunity by 
 means of toxins obtained by nitration of the cultures through 
 porcelain. Dr. Vinay resorted to the latter procedure. Finally, 
 Marmorek injected into the veins progressively increasing doses of 
 living cultures of his highly virulent streptococcus. 
 
 All these methods are evidently good. Drs. Denys, Leclef, and 
 Marchand, who took up the question and prepared serums by means 
 of living cultures or of toxins, obtained very encouraging results 
 in both cases. The only point that now requires investigation is 
 whether the serums are more efficacious when they are prepared 
 by one or the other of these various procedures and whether all 
 are equally harmless. The serum obtained by means of living 
 cultures has at times caused abscesses and erysipelas patches at 
 the point of injection. This result is due to the persistence of the 
 streptococci. This inconvenience is not. however, of a nature to 
 
 1 Charriu et Roger. Essai d 'application de la serumtherapie an traitement de la fidvre 
 puerperale. Soeiete de biologie, February 23, 1S95. p. 124. 
 
 3 Marmorek. Le s£rum antistreptococcique. Ibid.. March SO. 1S95. p. 230. 
 
718 INFECTIOUS DISEASES. 
 
 cause abandonment of the method, but it is well to be aware of the 
 fact and take some precautions — to wait longer before bleeding the 
 animals or to filter the serum through porcelain. 
 
 In order to prove the action of the serum it was thought that 
 cases of erysipelas should be experimented upon. Hence, Dr. 
 Chantemesse employed the serum of Marmorek in 501 cases, and the 
 death-rate was 2.59 per cent. A close examination of these facts 
 permits a division of them into three groups: The first includes 
 those cases in which the serum employed had a strength of 1 per 
 7000, with a death-rate of 1.68 per cent. The second comprises 
 those cases in which the serum had a strength of 1 per 2000, with a 
 mortality reaching 6.54 per cent., that is, a far greater percentage 
 than by usual treatment. Finally, by a new serum having a strength 
 of 1:30,000 the death-rate fell to 1.03 per cent. 
 
 Some objections were raised against these results. Dr. Bolognesi 
 remarked that just as favorable results may be obtained by the 
 simplest treatment. In the wards of Juhel-Renoy the death-rate 
 did not exceed 3.5 per cent., and occasionally, it fell to 1.21 and 
 even to 0.9 per cent. As a matter of fact, it is evident that an 
 adult of good constitution does not generally die from erysipelas. 
 The aged persons who succumb had, for the most part, some organic 
 lesion, particularly of the liver. 
 
 The serum should, therefore, be reserved for grave cases in which 
 it may render service, for cases characterized by relapses and in 
 prolonged forms, as well as for erysipelas of the newborn, although 
 in this last instance it does not seem to be very efficient. 
 
 The action of the serum in cases of surgical and puerperal septi- 
 cemias deserves particular study. Puerperal fever is of far more 
 frequent occurrence than is generally believed. From 1884 to 1893 
 the statistics of the city of Paris registered 3000 deaths due to this 
 cause. This is under the real figures, as a good many cases go under 
 different designations. The results obtained with the serumtherapy 
 treatment have been quite variable. This could be well foreseen, 
 since intervention takes place too tardily in most cases, or the case 
 is one of mixed infection, or perhaps, insufficient doses of the serum 
 are employed. After the publication of our results very encouraging 
 observations were reported by Drs. Josue and Herniary, Jacquot, 
 Marmorek, Chrobak, Vinoy, Denys, and Leclef .* On the other hand, 
 
 1 Denys and Leclef. Sur le serum antistreptococcique (report by Rommelaere) . 
 Acad, de Med. de Belgique, December 28, 1895. 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 719 
 
 in tin; Obstetrical Society of France (April, L896), the majority 
 obstetricians related rather disappointing observation . Charpentier 
 had had a death rate of 35 per cent., Bar and Ti Bier 60 peT cent. 
 In the cases which we treated the re all were far better. Our 
 statistics, which have the defecl of being too small, containing only 
 twelve cases of puerperal fever, may be divided into »ups: 
 
 Those in which ihi' treatment was insufficienl i. e. } in which too 
 small amounts of serum were injected. Such were twi one 
 
 of whom died. In the other ten cases the treatment, which was 
 at times tardily instituted, yielded nine recoveries and only one 
 death. Several of these patients would have recovered withoul the 
 serum. Several others, however, presented symptoms of extreme 
 gravity; one, among others whom Prof. Pinard was called to 
 was pronounced to be in a hopeless state. In order to obtain thera- 
 peutic effects, considerable doses of the serum musi be employed: 
 the introduction of 60 C.cm. per day •'!() in the morning and .';<) in 
 the evening. In one case we injected without any inconvenience 
 300 c.cm. in four clays. The patient, who was comatose at the 
 moment of intervention, recovered and was seen by us ten months 
 later. She presented no disturbance in consequence of this active 
 treatment. The effects of the serum are observed in the local lesione 
 as well as in the general condition of the patient. Locally, the vulval 
 wound modifies, the congestion disappears, and the wound assumes 
 a good aspect. In one case the pseudomembranes which covered 
 the vulva and vagina, and were quite intimately adherent to the 
 mucous membrane, were easily detached, exactly as when anti- 
 diphtheritic serum is injected in cases of anginas. At the same 
 time the general state is improved, the patients experience a feeling 
 of exhilaration, and the skin becomes moist. The modifications in 
 the temperature are quite variable. In some instances fever was 
 not influenced. In other cases it fell gradually or abruptly. In all 
 the successful cases, convalescence, which is usually so long after 
 puerperal fever, was remarkably shortened. 
 
 We may conclude from our personal observations that antistrepto- 
 coccic serum is a useful auxiliary in the treatment of puerperal fever. 
 We believe, however, that it should not be employed to the exclusion 
 of all other therapeutic measures: and we do not accept this mode 
 of action with reference to diphtheria in which it is far more justifi- 
 able. We think that all measures of treatment should be utilized, 
 and, according to the cases and the indications of each, curettage 
 
720 INFECTIOUS DISEASES. 
 
 may be employed, which may remove placental fragments often 
 filled with microbes of all descriptions, as well as intra-uterine 
 irrigations, gastrointestinal antisepsis, and, above all, cold baths. 
 Observations taken under these conditions would necessarily be 
 less clearly demonstrated and more complex; but what we must 
 look for is not the demonstration of the efficacy of a method at the 
 risk of the patients' lives. It would not be right to make such 
 experiments. Our duty is to benefit those under our care by all 
 therapeutic means at our disposal. In order to obtain results from 
 the serum we must not wait until the last moment. On the con- 
 trary, we should intervene from the very beginning of manifestations, 
 and inject large doses, and combine serumtherapy with the other 
 methods of treatment. Such is, in our opinion, the line of conduct 
 to be followed in the presence of puerperal fever, or rather of a 
 puerperal woman suffering from fever. It is hardly necessary to 
 say that even under these conditions we cannot save every patient, 
 and this for several reasons: puerperal fever is not always due 
 to the streptococcus. It often depends upon bacterial association. 
 Besides the streptococcus, there may be found the staphylococcus, 
 the pneumococcus, the pneumobacillus, the colon bacillus, the septic 
 vibrio, etc. Nevertheless, the serum seems to be efficacious against 
 at least one of these microbes; that is, the pneumobacillus. We 
 have observed three instances of this kind. 
 
 One of them concerned a woman who had an attack of very 
 grave puerperal fever. The symptoms rapidly yielded after two 
 injections of the serum, 30 c.cm. each. Examination of the lochia 
 did not reveal any other microbes than the pneumobacillus. 
 The second case was that of a puerperal woman, in the lochia of 
 whom both streptococcus and pneumobacillus were found. One 
 injection sufficed to overcome all the disquieting symptoms. 
 The last instance concerned a woman suffering from a suppurative 
 salpingitis, upon whom laparotomy was practised and the tubes 
 were extirpated. During the operation the tubal abscess burst and 
 the pus spread into the peritoneum. Septicemic phenomena devel- 
 oped, and on the following day, the patient being in a very serious 
 condition, antistreptococcic serum was injected into her. In four 
 days the manifestations subsided. Examination of the pus revealed 
 the presence of the pneumobacillus alone. 
 
 The cultures obtained from this last case were highly virulent. 
 One cubic centimetre when injected into the veins caused death 
 
THEBAPEXJTI08 OF INFECTIOUS DISEASES. 721 
 
 in rabbits within twenty four or thirty is hour . Pour or five cubic 
 centimetres of antistreptococcic serum, injected al the Bame time 
 that the inoculation was made, sufficed to save the animals. The 
 dose may seem too high, Tins experimental result, however, i 
 entirely in harmony with clinical observations. Still, it U nol to be 
 concluded that antistreptococcic serum is efficacioui against the 
 pneumobacillus. M was such againsl these samples, and even in 
 the three cases if acted far more rapidly and energetically than 
 when we employed it in infections due to the streptococcus. 
 
 Our last observation lends us to say a word regarding the employ- 
 ment of the serum in surgical septicemias. The rules are the same 
 us in puerperal fever. The results which we obtained were very 
 satisfactory. The serum was tried in three cases, and all recovered. 
 Marmorek also obtained successful results under the same conditions. 
 
 The .serum has not yet been used in cases of diffuse phlegmons 
 or streptococcic suppuration. It is not likely thai it would prove 
 efficacious. Likewise, we know very little as to its role in cases of 
 bronchopneumonia. A few attempts were made in scarlatina by 
 Marmorek, Josias, and Baginsky. The results were quite uncertain, 
 which is not to be wondered at, since it is not known what role is 
 played by the streptococcus in scarlatinal manifestations, even in 
 the anginas. 
 
 We have expounded at some length upon antistreptococcic serum- 
 therapy, because a future seems to be reserved for this method. 
 No doubt the results are not yet perfect. They will be better when 
 more active serums are obtained, and particularly when the treat- 
 ment is instituted from the very start of the morbid manifestations. 
 It is evident that success is not to be expected in every case, since 
 the infections are sometimes mixed, and the serum cannot be effi- 
 cacious against all the streptococci. An animal which is immunized 
 against one variety, furnishes a serum that is powerless against the 
 other varieties. It is well, therefore, to immunize animals by inject- 
 ing cultures obtained from various sources. Such is the method at 
 present employed by Denys. Lastly, as regards puerperal infection, 
 we must take into consideration the role of the living microbes and 
 that of the bacterial toxins. Numerous examples, notably the study 
 of cholera cases, show that, according to the procedures of immuniza- 
 tion, the animals furnish either germicidal or antitoxic serums, that 
 is to say, sera acting upon the living microbes or upon their secre- 
 tions. Hence, it is necessary to prepare serums endowed with both 
 
 46 
 
722 INFECTIOUS DISEASES. 
 
 of i hose properties, so that the antitoxin may combat the action of 
 harmful products already diffused in the organism, while the anti- 
 bacterial substance hinders the further development of the figurate 
 elements. 
 
 Tetanus. Antitetanic serum is also the work of Behring and 
 Kitasato. .Those authors discovered the means of immunizing 
 against the microbe. They succeeded with toxins treated with 
 trichloride of iodine or cultures prepared in thymus gland bouillon. 
 Immunity was subsequently obtained by other procedures as well. 
 Vaillard employed filtered cultures which were attenuated by heat 
 between 122° and 140° F. (50° and 60° C). Roux and Vaillard 
 employed, as in diphtheria, a mixture with iodized water.. 
 
 The serum of vaccinated animals was first studied by Behring 
 and Kitasato, who recognized that it possessed the same property 
 as the antidiphtheritic serum. It neutralizes poisons — i. e., it is 
 antitoxin. This result immediately led to therapeutic investigations, 
 since, as is known, tetanus is one of the infectious diseases in which 
 intoxication plays the principal role. The results obtained by 
 Behring and Kitasato at first appeared very encouraging. These 
 authors declared that antitetanic serum protects the animal into 
 which it is injected against tetanus, and may even cure the estab- 
 lished disease. They asserted that it was possible to save a mouse 
 already presenting the characteristic contractures. 
 
 These experiments, however, were controlled by Tizzoni and 
 Cattani, Vaillard, and then by Kitasato himself, but gave negative 
 results from a therapeutic standpoint. Roux and Vaillard subse- 
 quently proved that the serum, when injected before inoculation, 
 protects the animals. When it is introduced coincidently with the 
 toxin or a little later, it attenuates the manifestations and permits 
 only a local tetanus. But it is absolutely inefficient when injected 
 into animals already presenting contractures. 
 
 This last result raises a theoretical question of considerable 
 interest. The inefficiency of the serum is not well understood if 
 it is admitted that the antitoxin neutralizes the toxin. On the 
 other hand, if it is supposed — and this is the prevailing theory — 
 that antitoxins act by increasing the resistance of the anatomical 
 elements, perhaps by preventing their impregnation, it is then con- 
 ceivable that injection of the serum will not suffice to arrest the 
 evolution of the disease. Sahli, whose theory is similar to that 
 advanced by Courmont and Doyon (p. 413), goes further. He 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 723 
 
 believes that the toxins are often eliminated when the manifestations 
 appear, but that they leave in thenervou j tem alteration which 
 follow an independent course The serum does not act upon these 
 lesions any more than the salicylate does upon rheumatic endo- 
 carditis. 
 
 The serum is employed rather as a preventive, h i employed 
 for man when a wound is contaminated by soil, particularly in 
 countries where tetanus is frequent or in individual who come in 
 contact with horses. In veterinary medicine ii renders aum< 
 services. It is often injected us a prophylactic into horsee which 
 arc about to be castrated. 
 
 The serum is still administered to man in subcutaneous injections, 
 and in largo doses in cases of established tetanus. Suca 
 recorded from time to time. Several such observations, however, 
 are liable to crilicisni. It has, therefore, been thought thai the 
 mode of introduction of the serum required some modification. 
 As a result of their investigations on cerebral tetanus, Rous and 
 Borrel conceived the idea of injecting the serum directly into the 
 cerebral substance of tetanic patients. Experiments pursued upon 
 animals seemed to demonstrate the value of the method. 
 
 The first application to man was made by Chauffard and Quenu. 
 The patient recovered. Two months later, Gamier published the 
 report of a successful case observed in our wards. It was a case 
 characterized by a slow course. During the first three days the 
 tetanus was benign. The fourth day, the state being aggravated, 
 we decided to intervene. Six cubic centimetres of concentrated 
 serum, equivalent to 15 corn, of the ordinary serum, were injected 
 into the two cerebral hemispheres. Simultaneously 116 c.cm. were 
 injected beneath the skin. At the end of three days amelioration 
 was manifest. Recovery was complete a month later. Conval- 
 escence was disturbed by psychic disorders and erotic delirium. 
 These phenomena were transitory. By collecting the published 
 observations, a death-rate of 75 per cent, was found: that is 
 larger than the average death-rate, which does not exceed 70 per 
 cent. As nothing regarding this method has been published for 
 some time, it may be supposed that it has been almost abandoned. 
 Is it at least inoffensive? The majority of authors suppose it to be 
 so. In the case of Gamier, however, psychic disorders, though of 
 a transitory character, developed in consequence of the injection. 
 In another case observed by us and published by Dr. Robert, death 
 
724 INFECTIOUS DISEASES. 
 
 occurred twenty-four hours after the injection. The necropsy re- 
 vealed acute edema of the meninges and, in one of the cerebral lobes, 
 a cavity filled with a sanguinolent fluid. It may well be asked 
 whether such a lesion in so delicate an organ may be considered 
 indifferent. 
 
 Instead of introducing the serum into the brain, Sicard injected 
 it into the lumbar subarachnoidal cavity. The results obtained in 
 dogs were very encouraging. In man the method does not seem 
 to have been successful. Thus we find, with reference to tetanus, 
 the antagonism which we noted on several occasions between the 
 results obtained in laboratories and facts of clinical observation. 
 This does not mean that the importance of experimental investiga- 
 tions is any less valuable; but it should be recognized that human 
 pathology is extremely complex, and, therefore, it is necessary to 
 pursue new researches and make new attempts. 
 
 Tuberculosis. Richet and Hericourt 1 were the first to attempt 
 antitubercular serumtherapy by injecting the blood of dogs into 
 the peritoneum of rabbits inoculated with cultures of avian or 
 bovine tuberculosis. The quantity of blood transfused varied from 
 16 to 41 grams. The mortality of the controls was 55 per cent., 
 and that of the transfused 17 per cent. Soon after, Bertin and Picq 
 made analogous attempts with the blood of goats, which are reputed 
 to be immune to tuberculosis. By employing 2.5 grams per kilogram 
 of animal they succeeded in preventing or arresting the develop- 
 ment of the disease. 
 
 These results were soon applied clinically, and a few successes seem 
 to have been obtained by subcutaneous injections of the blood of 
 dogs and goats. In spite of these encouraging results, the employ- 
 ment of the blood of normal animals did not lead to a definitive 
 method. The serum of naturally immune animals almost never 
 possesses true curative power, for the reason that natural immunity 
 is always contingent and is never absolute. In regard to tuberculosis, 
 this law is the more accurate, as we know of no mammalian that is 
 endowed with a notable resistance. The serum of the gallina3, the 
 only animals enjoying a certain immunity, does not possess the 
 power of arresting the evolution of tuberculosis in mammalia into 
 which it is injected. Extracts of the organs have not proved to be 
 any more efficacious. 
 
 1 Hericourt and Richet. Influence de la transfusion pe>iton6ale du sang de chien sur 
 Involution de la tuberculose chez le lapin. Society de biologie, March 2, 1889. 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 725 
 
 Experimenters were, therefore, led to investigate whether it 
 possible, l>y various procedures, to confer artificial therapeutic 
 power upon the serum of certain animals. A good many attempts 
 were, made in this direction. In spile of their apparenl multiplicity, 
 the procedures employed are divisible into three groups: I . Employ- 
 ment of living cultures. 2. Employmenl of iterilized cult 
 3. Mixed method, in which both soluble products and living culture* 
 are made use of. 
 
 1. The Serum of Animals Treatedwith Living Cultures. This pro- 
 cedure was variously u1 ilized. I [ericourl and Richel , having obtained 
 a relative immunity in dogs which had received avian tuberculosis, 
 were naturally led to study the therapeutic action of their Quids. 
 They employed the serum obtained by modulating avian tubercu- 
 losis beneath the skin of the dog. This fluid, which the authors 
 called phymoserum, when freed from leucocytes, is found to po 
 well-marked immunizing properties with regard to rabbits. The 
 authors, however, seem to have abandoned this method in order to 
 prepare a neoserum with animals inoculated with human tubercu- 
 losis. 
 
 The procedure of Hericourt and Richet consists in inoculating with 
 human tuberculosis animals of slight susceptibility, such as asses and 
 dogs. In a first series of experiments the serum was furnished by 
 an ass which received, one month previously, an injection of virulent 
 human tuberculosis. AVhile the control guinea-pigs died at the end 
 of two months, out of four guinea-pigs treated, two were still living 
 at the end of seventy-one clays. In another note the authors an- 
 nounced that they had inoculated dogs with tubercle bacilli pre- 
 viously freed from tuberculin by washing. The inoculations were 
 made into the veins, and the animals were bled at the end of ten 
 days. The serum was used to treat a woman, thirty-four years of 
 age, in whom a very manifest amelioration was observed. A few 
 months later Redon and Chenot announced that it was possible to 
 prevent tuberculosis in rabbits and guinea-pigs by injecting into 
 them the serum of asses or mules which had previously been inocu- 
 lated with tuberculosis and presented no lesion in consequence of 
 this operation. The results were still better when the serum of horses 
 first treated with tannin was used than when active tubercular virus 
 was employed. 
 
 Evidently here are very interesting results which are. nevertheless, 
 open to criticism. The dog, the ass, the mule, and the horse are far 
 
726 IXFECTIOUS DISEASES. 
 
 from presenting a natural resistance as pronounced as was once 
 believed. In those cases in which dogs and goats withstood virulent 
 inoculations and in those instances in which animals of this same 
 species presented only very discrete lesions, Silvestrini obtained no 
 notable effect by treating tubercular guinea-pigs with their sera. 
 With Cadiot we tried, with no greater success, the serum of an ass 
 which presented a voluminous local lesion produced by inocu- 
 lation of human tuberculosis. The guinea-pigs which received the 
 serum died more rapidly than the controls. On the other hand, 
 Broca and Charrin obtained encouraging results in man. The serum 
 employed was that of dogs suffering from a local tubercular lesion. 
 The injections, when made into patients affected with lupus or 
 fungous ulcerations consecutive to incomplete surgical intervention, 
 produced notable amelioration in the lesions. 
 
 How are these favorable results to be explained? Can it be 
 assumed that the serum acted simply like the normal serum of the 
 dog, which also possesses the power of improving cutaneous tuber- 
 culosis (Feulard)? This interpretation is inadmissible. It is well, 
 however, to take into account the possibility of an action comparable 
 to that of tuberculin. In fact, it seems that in the course of tuber- 
 culosis the blood contains a substance analogous to that extracted 
 by Koch from cultures of his bacillus. The blood of tubercular dogs 
 possibly represents a dilution of tuberculin which is too weak to 
 give rise to dangerous reactions, but sufficient to ameliorate local 
 lesions. This explanation seems to me the more admissible, since 
 Koch's lymph is most efficient in lupus and external tuberculosis. 
 
 While virulent cultures do not seem to yield good results, it may 
 be hoped that attenuated cultures will prove more satisfactory. 
 Researches published by Schweinitz and Dorset tend to prove this. 
 Two horses received considerable quantities of attenuated cultures 
 — as much as 4590 c.cm. in eight months. The serum of the animals 
 thus treated possessed the power of prolonging the life of tubercular 
 guinea-pigs and even of saving some of them. 
 
 2. Serum of Animals Treated with Sterilized Cultures, Extracts, 
 Tuberculin, etc. In view of the principle that the presence of a poison 
 causes the elaboration of an antitoxin in the organism, it was natural 
 to investigate what would happen in animals as a result of injection 
 of tubercular poison, notably tuberculin. Hericourt and Richet 
 experimented with the serum and milk of female asses which had 
 previously been injected with Koch's lymph. The animals treated 
 
THERAPEUTICS OF INFECTIOUS DI8EASES. 727 
 
 with these products succumbed more rapidly than the controls. A 
 few months later, Dr. Boinel announced thai the erum of tubercu- 
 linized goats protected guinea -pigs into which an inoculation of viru- 
 lent tuberculosis was afterward made. When employed inpatients 
 the serum produced amelioration in mild forms of tuberculoses, bul 
 it was ineffective in individuals with cavities and in those presenting 
 febrile movements or hemoptysis. 
 
 The presence of an antituberculin in the blood of animals treated 
 with tuberculin was proved especially by the investigation* of Behr- 
 ing and of Niemann. I'ehring, in collaboration with Wernicke and 
 Knorr, found antifuberculin in the blood of man and animals which 
 had been injected with progressively increasing amounts of tuber- 
 culin. In order to demonstrate Ibis these authors injected fatal doses 
 of tuberculin into tubercular guinea-pigs. Those animals which 
 received the scrum at the same time the tuberculin was injected did 
 not die. Niemann published analogous experiments. He resorted 
 to very different animals — dogs, goats, guinea-pigs, white rats, por- 
 cupines — and injected into them progressively increased doses of 
 tuberculin, or, still better, a precipitate obtained by mean- of alcohol, 
 so as to free it from glycerin. He thus conferred upon them a certain 
 immunity against virulent inoculations. He then tried the serum 
 upon tubercular guinea-pigs, with the following results: 40 eg. of 
 tuberculin killed the animals in a period of time varying from four- 
 teen to seventeen hours. The same dose, when mixed with 8 c.cm. 
 of the serum killed the animals in twenty or thirty hours. "With 
 10 c.cm. the animals lived twenty-two days, and with 12 c.cm. from 
 thirty-five to forty-two days. Finally, 6 grams of serum of a goat 
 which had received tuberculin and dead bacilli preserved the lives 
 of the animals for from fifty to seventy days. 
 
 Maffucci and Di Vestea injected into sheep 456 mg. to 1670 mg. 
 of bacilli killed by exposure to a temperature of 230° F. (110° C.) 
 for twenty minutes. Living bacilli placed in contact for half an hour 
 with the serum taken from these animals lost part of their virulence. 
 Guinea-pigs which were inoculated with the mixture died far mure 
 slowty than those which received only the bacilli or those which 
 received the bacilli and the serum separately. The latter, how- 
 ever, survived a little longer than the controls. It would seem, 
 therefore, that under the influence of tubercular products there is 
 formed in the organism a substance possessing the power of at- 
 tenuating the action of tubercular toxins and even of the living 
 
728 IXFECTIO US DISEA SES. 
 
 bacilli. In the latter ease the two products must be previously mixed 
 in vitreo. 
 
 3. Mixed Method. As early as 1892 Babes and Broca conceived 
 the idea of preparing animals by means of injections of avian and 
 human tuberculin, then by inoculating into them avian tuberculosis, 
 and, lastly, human tuberculosis. The blood and the serum taken 
 from dogs, rabbits, guinea-pigs, and cows treated in this manner 
 neutralized tuberculin and prevented or cured tuberculosis in rabbits 
 and guinea-pigs. The employment of these fluids produced good 
 results, even in man; the fever ceased, the weight increased, and the 
 cutaneous lesions, notably lupus, improved. 
 
 Antitubercular Serumtherapy in Man; the Serum of Maragliano. 
 As has already been stated, several authors had obtained in man 
 more or less marked improvements. Hericourt and Richet, as well 
 as Boinet, utilized the serum of animals the resistance of which they 
 thought they had increased. Paquin prepared a serum of equine 
 origin. Bloch advocated the employment of the blood taken from 
 the subcutaneous capillary network. The investigations of Marag- 
 liano placed the question upon a practical basis. In the first place 
 this author established that tubercular cultures contained two kinds 
 of toxic substances. Some of them, which are obtained by concen- 
 trating the culture at 212° F. (100° C), are represented by proteins 
 derived from the bodies of the bacilli. These are the substances 
 found in Koch's lymph. The others, which are prepared by concen- 
 trating in vacuo at 86° F. (30° C.) and filtering the culture through 
 porcelain, are particularly toxalbumins. This latter fluid manifests 
 an action altogether opposite to that of the former. It kills the 
 animals in a state of collapse, while tuberculin produces hyper- 
 thermia. 
 
 The animals which furnish the serum — goats, asses, and horses — 
 are injected with progressively increasing doses of a mixture of three 
 parts of the former and one part of the latter fluid. At the end of 
 six months immunization is obtained, and three or four weeks after 
 the last injection, venesection is practised. The serum is germicidal 
 as well as antitoxic. It annihilates the toxic action of tuberculin. 
 In a normal guinea-pig 1 gram of the serum neutralizes a fatal dose 
 of tuberculin. In tubercular guinea-pigs, which succumb to a ten 
 times smaller dose of tuberculin, it is necessary to inject 2 to 4 grams 
 of the serum per kilogram of animal in order to save them. As 
 regards tubercular human subjects, the dose of tuberculin which 
 
THERAPEUTICS OF INFECTIOUS DI8EA8ES. 12'.) 
 
 causes fever is neutralized by I c.cm. of the serum. After they have 
 I )fcn treated l>y the serum the tuberculous individual become in en- 
 sible to IIk' action of tuberculin, even when use i made of 'I'' e ten 
 times larger than those which, ;ii Hi'' beginning, gave rise to reaction* . 
 The treatment consists in injecting into the patienl I c.cm. every 
 other day. In febrile cases in which no reduction in the temperature 
 is obtained, the doses are increased t<> 5 c.cm. and 10 c.cm. If the 
 fever disappears the dose is again reduced to I c.cm. This dose i- 
 to be employed if the febrile process is not arrested by higher d< 
 This treatment should be stopped in case of hemoptysis. A greal 
 number of physicians made use of Maragliano's serum, and the obser- 
 vations published are quite favorable to the method. The serum 
 proved useful in 01 per cent, of the cases, and it proved curative in 
 1G per cent . 
 
 It is evidently too soon to conclude Hint Marnglinno's serum is the 
 true specific of tuberculosis. Numerous negative facts do not permit 
 such optimism. The fact that may at once be recognized is that the 
 medicine when employed in amounts indicated by the author does 
 not seem to be dangerous and is at times efficacious. Perhaps the 
 failures are due in part to the fact that in man the process is always 
 complex. Besides tuberculosis, a whole series of secondary infect ions 
 are to be combated. Here is the stumbling-block of antitubercular 
 serumtherapy. The day we possess a serum capable of combating 
 or destroying Koch's bacillus we shall still lack an infallible serum 
 against tuberculosis, for, barring the cases of acute miliary tubercu- 
 losis, the infection is mixed, and, when it has reached the third stage, 
 the patient that has pulmonary cavities and is suffering from hectic 
 fever is a pyohemic rather than a bacillary sufferer. A whole series 
 of serums, varying from one case to another, must be employed in 
 a polymicrobic infection. The impossibility if not the dangerous 
 character of such therapeutics is evident. 
 
 Typhoid Fever. It is not difficult to vaccinate animals against the 
 bacillus of Eberth. This may be accomplished by employing the 
 living microbes, as has been done by Beumer and Peiper, or by 
 making use of sterilized cultures, as was advised by Chantemesse and 
 Widal, Brieger, Kitasato, and Wassermann. The majority of authors 
 to-day resort to the latter method. In order, however, to obtain an 
 active serum, an exalted virus must be employed. The best means 
 consists in making passages in series on animals, by favoring the 
 development of the pathogenic agent by means of simultaneous injec- 
 
730 I - v I'ECTIO US DISEA SES. 
 
 tions of microbic toxins. These toxins are of two orders. Some are 
 contained in the bodies of microbes. Funck makes use of these for 
 immunizing animals. On the other hand, Chantemesse utilizes the 
 poisons fchat diffuse into the culture bouillon. By means of a special 
 mi', lium he obtains a very active toxin which enables him to immun- 
 ize horses, but the experiment is extremely long. It was only after 
 two years of preparation that Chantemesse obtained a truly active 
 serum. Klempcrer and Levy, with the serum of dogs, and Borge, 
 with a serum of sheep prepared by Beumer and Peiper, succeeded in 
 shortening the morbid evolution. 
 
 Chantemesse, after establishing the immunizing and curative power 
 of this serum upon animals, obtained very encouraging results in 
 man. One-fiftieth of a cubic centimetre of the serum injected as a 
 prophylactic into a guinea-pig confers immunity against a fatal dose 
 of toxin. When he injected into guinea-pigs a dose of toxin which 
 killed the controls in twenty-four or forty-eight hours, the guinea-pigs 
 which subsequently received 25 eg. of serum four and even five hours 
 after introduction of the poison usually resisted. 
 
 In man the treatment reduced the mortality to less than 6 per 
 cent. The study of observations and of the course of the fever 
 demonstrates the efficiency of the method more than statistics. An 
 injection of from 10 c.cm. to 20 c.cm. of serum suffices to lower the 
 temperature and cause the diazo reaction to disappear. The duration 
 of the disease is shortened. Defervescence occurs early, and, contrary 
 to what usually happens, the urine remains scanty for several days 
 after the fall of the fever. 
 
 Infections the Agents of Which are Unknown or Not Well Known. 
 We place in a separate group those infectious diseases the microbes 
 of which are unknown, or little known, or have not been cultivated. 
 Numerous attempts have been made in such cases, by employing 
 the blood and the serum of convalescent men or of animals into 
 which virulent products obtained from man had been injected. 
 
 Eruptive Fevers. The eruptive fevers, such as measles and scarla- 
 tina, are not transmissible to animals. Kelaidites injected into 
 heifers the blood and squamae of scarlatinal patients. From 20 c.cm. 
 to 30 c.cm. of the serum of animals thus treated sufficed to arrest 
 the course of the infection. The same author prepared a serum 
 against whooping-cough by injecting into dogs the bronchial and 
 nasal secretions of patients. In most cases the serum of convales- 
 cents was made use of for therapeutic purposes. This is what we 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 7:; I 
 
 accomplished in several cases of scarlatina. The method is quite 
 simple and appears to be efficacious, as may be judged from the 
 following observal ion :' 
 
 At 8 p.m. on June 17, L896, a young man, fifteen year ol age, 
 was brought fco our wards suffering from scarlatina. The attach 
 had taken place forty-eight hours previoui ly and had been ushered 
 in by vertigo, headache, and sore throat. At the time of bU admis 
 sion we were struck by the gravity of the general Btate. The 
 patient was motionless and semicomatose. From time to time 
 his limbs were shaken by slight convulsive movements, his face 
 drawn, his eyes fixed, and dyspnea whs extremely intense. S 
 eight respiratory movements ;i, niinule were count c<\ ;md l_'0 regular 
 and quite strong heart-boats. The. skin \v;is covered with ;i general- 
 ized scarlatinal erupt ion. The tongue was dry and the tonsilfl swollen 
 and covered with a pultaceous deposit. After his arrival the patienl 
 voided a small amount of non-albuminous urine. Owing to the 
 gravity of the general state our interne gave, at 10 p.m., a subcu- 
 taneous injection of 400 grams of salt-water; at 1 a.m. a bath was 
 given at 82.4° F. (28° C). 
 
 On the morning of the 18th the general state was about the same 
 as on the previous evening. The patient was comatose, and his 
 extremities were at times convulsed, the tongue dry, the tempera- 
 ture, taken every three hours, was reduced after the administration 
 of the bath, then it rose and, in the morning, reached 10.5.3° F. 
 (40.2° C). The number of respirations was 68; the pulse did not 
 exceed 120, but was extremely weak. The patient had voided no 
 urine since the previous night. 
 
 A fatal termination seemed to be approaching. We resolved to 
 employ serum treatment. A man convalescent from scarlatina was 
 willing to furnish the blood. As, however, it was necessary to act 
 promptly, we could not prepare serum. Hence, we decided to inject 
 defibrinated blood. For this purpose we took a glass ball, and. after 
 introducing into it a certain quantity of pearls, closed it with 
 cotton. The ball was sterilized at 356° F. (180° C). The vein of 
 the convalescent was then opened and 100 grams of blood drawn. 
 By gently agitating the ball the pearls separated the fibrin, and an 
 aseptic fluid was thus obtained. These preparations had taken an 
 horn. During this time the state of the young man had become still 
 
 1 Roger. Quelques reflexions sur le traitement des searlatines graves. Essai de 
 s£roth6rapie. La presse medieale. 1S96. 
 
732 INFECTIO US DISEA SES. 
 
 worse, and a fatal issue seemed imminent. At 11 a.m. we bled the 
 patient and took from him 150 grams of blood. Eighty cubic centi- 
 metres of defibrinated blood taken from the convalescent were then 
 injected beneath the skin of the abdomen. 
 
 At 4 p.m.. when the author saw the patient, he found him sleeping 
 and breathing quietly ; he then awoke and, having made a few move- 
 ments, the respiratory rhythm changed and assumed the type of 
 Chcyne-Stokes. The pulse-beat was 120 and weak, although less so 
 than in the morning. Prostration was less marked and the tongue 
 had become moist. In spite of this notable amelioration of the gen- 
 eral state, the temperature remained high and the patient passed no 
 urine. He was then given a bath at 82.4° F. (28° C). The tempera- 
 ture then began to fall. At 7 p.m. 400 grams of salt water were 
 injected beneath the skin. At 8 p.m. he passed urine. At 10 p.m. 
 the interne found the patient sleeping quietly, his pulse 100, respira- 
 tions 25 per minute. On the following morning the patient was 
 found completely transformed ; he spoke easily, felt well, and asked 
 for food. The tongue was desquamated but moist, and the eruption 
 was pale, except in the lower extremities, where it was still marked. 
 The pulse, 80 per minute, was still somewhat weak, but very regular, 
 and the respiration 22. Finally, since 8 o'clock of the previous even- 
 ing until 8 o'clock the next morning, the patient voided 1100 c.cm. 
 of a dark red, non-albuminous urine. The temperature oscillated 
 during the day around 100.4° F. (38° C), and on the following day 
 it returned to the normal in a definitive manner. On the following 
 days nothing special was noted. The infection was shortened, and 
 in so serious a case we have never seen so rapid a convalescence. 
 
 When recovered the patient told us that he did not remember his 
 arrival at the hospital or the salt-water injection given him at 
 that time. He remembered only the bath which had been given at 
 night. This consciousness, however, had not lasted long, for the 
 patient could not recall the bleeding nor the injection of defibrinated 
 blood. He had come out of his comatose state later in the day. He 
 clearly had kept the remembrance of my visit of 4 p.m. and all the 
 events taking place after that time. These retrospective details are 
 interesting inasmuch as they show the extreme gravity of the situa- 
 tion at the time of intervention. It may be said that our observation 
 is too complex, since recourse was had simultaneously to several 
 therapeutic methods. This mode of action renders demonstrations 
 less exact, but it was the only one permissible. By studying the 
 
THERAPEUTICS OF INFECTIOUS DISEASES. i:',\', 
 
 evolution of the disease, however, it. is possible to di cern whal U due 
 to each procedure cm ployed, [mprovemenl began after the injection 
 of the blood and, unless it, is assumed thai the change in the general 
 state would have occurred even withoui intervention, which is among 
 the possible events, the amelioration is to be attributed to the 
 influence of the hemotherapy. The improvemenl thu started con- 
 tinued, owing to the auxiliary action of the bath and especially to 
 the injection of salt-water. 
 
 The same hemotherapic method is applicable to measles. In f'»ur 
 cases Weisbee.ker saw rapid arrest of bronchopneumonias "I measles 
 under the influence of the serum of convalescenl individuals. These 
 researches are the more important as (hey were made on very young 
 children — i. c, under particularly grave conditions. The rapid dis- 
 appearance of the thoracic manifestations leads to the question 
 whether bronchopneumonia is really, as is generally admitted, exclu- 
 sively dependent upon secondary infection, or whether, ,i~ hr. I -' -■■ ■ ir< • 
 thinks, the principal agent of the disease plays a more important 
 role in its development than is generally supposed. 
 
 Analogous methods have been employed against recurrent fever, 
 (Gabritchewski), typhus fever (Lewaschew, Hammerschlag, v. 
 Jaksch, Legrain), and acute articular rheumatism (Weiss). The 
 observations are too small in number to justify discussion of these 
 attempts at length. 
 
 Vaccine and Variola. Sternberg is to be credited with having 
 demonstrated the properties acquired by the serum as a result of 
 Jennerian vaccination. This author, whose investigations were con- 
 firmed by Kinyoun, recognized that a drop of vaccine when mixed 
 with four drops of serum of a calf vaccinated for two weeks, loses, 
 at the end of an hour of contact, the power of causing vaccinal erup- 
 tion. 
 
 This was the first step in the way of serumtherapy. The authors, 
 however, who attempted to immunize animals by means of the serum 
 of vaccinated subjects obtained results which were not very satis- 
 factory. We must come to the important work of Beclere, Chambon, 
 and Menard, 1 who demonstrated that the serum of a vaccinated calf 
 when not taken during the virulent period — i. c, from ten to fifteen 
 days after vaccination — possesses, with regard to the inoculated vac- 
 cine, immunizing properties, provided very considerable amounts of 
 
 1 Beclere, Chambon. and Menard. Etudes sur l'immuiiite vaccinale et le pouvoir 
 immunisant du serum de g&risse vaccinee. Annates de l'Institut Pasteur, January, 1896 
 
734 IXFECTIOUS DISEASES. 
 
 serum are introduced beneath the skin. It is necessary to inject an 
 amount equal to one-hundredth part of the weight of the body, and 
 even then the immunity obtained is incomplete. A great number of 
 inoculations are ineffective. The eruptions which appear are rudi- 
 mentary. However, the most important fact from a doctrinal stand- 
 point is that- the contents of these eruptions are not virulent. They 
 cannot be employed to inoculate other individuals. The authors 
 furthermore remark that the action of the serum depends rather 
 upon the substances which are dissolved in it, since the effects are 
 immediate. Twenty-four hours after the injection immunity is 
 effected. 
 
 It is evident that serumtherapy cannot displace Jennerian vac- 
 cination, and this for two reasons : the amount of serum required is 
 too great; the immunity produced is incomplete and is not permanent. 
 Serumtherapy may, therefore, be resorted to only in those cases in 
 which non-vaccinated individuals are found in contact with variolar 
 patients, especially if they present at that moment some morbid 
 symptoms announcing the invasion of variola. It would then be 
 feared that vaccine would act too tardily to modify the organism in 
 time. The serum is to be utilized under such conditions and, if 
 necessary, an inoculation with the vaccinal virus made at the same 
 time. 
 
 The authors, however, who studied the vaccinal serum, had 
 another end in view. They looked for a remedy against variola. As 
 early as 1893 Auche, and then Landmann employed human serum 
 obtained from cured variola cases. They obtained no appreciable 
 result. Landmann likewise failed with the serum of vaccinated 
 heifers, while Elliot saw a patient recover without trny cicatrices 
 after the injection of 105 c.cm. In another case, which was a very 
 grave one, 65 c.cm. did not prevent the fatal termination. According 
 to Beclere, the failures are due to the fact that the amount of serum 
 administered is too small. This author injected amounts far exceed- 
 ing those employed in other diseases. He made use of doses equiv- 
 alent to one-fiftieth part of the weight of the body in adults, and to 
 the twentieth part in children. Thus, in a case reported by him, 
 a woman weighing 70 kilograms (155 pounds) received 1560 c.cm. 
 beneath the skin of the abdomen in one hour. This patient bore the 
 injection well and rapidly recovered. Beclere, during the Marseilles 
 epidemic, treated ten cases of variola. Three of them died; one of 
 them, however, had from the beginning a hemorrhagic variola, the 
 
THERAPEUTICS OF INFECTIOUS DI8EA8E8. 735 
 
 other was a newborn suffering from athrepsia. We may add to the 
 list a few cases treated by Dr. B^clere in our isolation ward al the 
 Hospital of La Porte d'Aubervilliers, everal of them with 
 
 Owing to his scientific temper, Dr. Be»cl6re abstain from drawing 
 any conclusions from his serumtherapy method. The facts are too 
 small in m mil xt to en: 1 1 ilc one to form a well founded opinion. There 
 is one thing, however, thai can meanwhile be affirmed, viz., thai the 
 method is harmless. The serum, even when administered in very 
 large amounts, is borne perfectly. Hence, there is no reason for not 
 continuing (he experiments. Of course, the patients should al the 
 same lime be (rented by the usual means, and the physician should 
 be glad to find a useful auxiliary in serumtherapy. In view of the 
 first results obtained and the recent investigations pursued by Dr, 
 Courniont, we may conclude that the action of the vaccinal serum 
 should be increased and rendered more energetic. Although the 
 calves submitted to repeated inoculations do not seem to furnish a 
 more efficacious serum, some results may, perhaps, be arrived al by 
 modifying the mode of introduction and by injecting, for example, 
 large amounts of vaccine into the circulatory system. 
 
 Hydrophobia. After the discovery of Richet and Hericourt. Babes 
 pursued a series of studies on antirabic serumtherapy. Then fol- 
 lowed Tizzoni, Schwarz, and Centanni, who added some important 
 data to the controversy. In their first experiments Babes and Lepp 
 recognized that a dog after having received for six successive days 
 5 c.cm. of blood of a vaccinated dog, becomes refractory to the inocu- 
 lation of hydrophobia. The result is the same in rabbits. After 
 allowing four clogs to be bitten by hydrophobic animals, the authors 
 kept two of them as controls. These died within sixteen and twenty- 
 eight hours, respectively. The other two received, for seven day.-. 
 the blood of the vaccinated animals; one of them died tardily, the 
 other resisted. This favorable action of the blood probably depends 
 upon a power which may be demonstrated outside of the organism. 
 Babes and Cerchez, and Tizzoni and Schwarz proved that when the 
 blood or the serum of a vaccinated dog is left for several hours in 
 contact with the virus of hydrophobia, the latter loses its pathogenic 
 properties. This action seems to be due to a globulin which is soluble 
 in glycerin, precipitated by the sulphate of magnesia and by alcohol, 
 ami does not pass through the membrane of the dialyzer 'Tizzoni 
 ami Schwarz). By employing strongly immunized animals we may 
 succeed in preparing a serum of very great activity. From this point 
 
736 IXFECTIOUS DISEASES. 
 
 of view, the serum of Tizzoni and Centanni seems to respond to all 
 requirements. It is prophylactic in the proportion of 1:25,000 for 
 an inoculation of hydrophobic virus practised twenty-four hours 
 later; in other words, 0.04 c.cm. suffices to immunize a rabbit weigh- 
 ing 1 kilogram. The proportion falls to 1 per cent, for the fixed virus. 
 From six to ten times larger doses must be employed in treating 
 animals already inoculated. These doses, however, are not excessive, 
 since, for a man, they would not exceed the amount of 20 or 25 grams. 
 
 It would, therefore, be advantageous to substitute serumtherapy 
 for the Pasteur method in those cases in which rapid action is 
 necessary. Such is the conclusion reached by various authorities 
 who have studied this question, notably that of Babes, who, since 
 1891, has employed this therapeutic method with success in patients 
 who had been bitten by hydrophobic wolves. 
 
 Syphilis. As all animals are refractory to syphilis, any species might 
 be chosen for the first serumtherapy attempts. The clog, the sheep, 
 the lamb, the calf, and the rabbit have been made use of. Their 
 sera have increased the strength of patients and hastened cicatriza- 
 tion of rebellious ulcerations. This is practically the same effect as 
 is at times produced by the serum of normal animals in tubercular 
 ulcerations. 
 
 The evolution of the disease, however, did not seem to be in any 
 wise influenced by these injections. A specific serum was, therefore, 
 looked for. Pellizzari then tried the method which yielded results 
 in other diseases. He injected the serum obtained from syphilitic 
 individuals infected for a greater or less period of time. The results 
 were insignificant, a fact undoubtedly due to the too small amount 
 of antitoxin contained in the blood of a syphilitic. Hence, it was 
 necessary to increase the therapeutic action of the serum. In this 
 direction an attempt was made by G. Mazza, by injecting into ani- 
 mals from 10 c.cm. to 20 c.cm. of S}^philitic blood. The author, 
 however, does not seem to have pursued his researches with much 
 persistence. The question was taken up by Drs. Richet, Hericourt, 
 and Triboulet, who prepared their animals — dog or ass — with the 
 blood of individuals presenting roseolar eruption. A few clays later 
 they bled the animals. Three patients were submitted to the treat- 
 ment. In this manner they obtained a more or less lasting cica- 
 trization of ulcerations which had resisted specific treatment, and in 
 one case they saw the disappearance of certain symptoms which 
 seemed to indicate the development of locomotor ataxia. 
 
THEBAPEUTIOS OF INFECTIOUS DISEASES. 7.",7 
 
 At that time Drs. Gilbert and Fournier published an important 
 work in which they described various serumtherapy proced 
 Into a newly infected syphilitic individual they injected within 
 twenty days 204 ecu], of serum taken from an old c ypb - 
 
 ilis. Under the influence of this treatment the general state im- 
 proved, the aching of the bones and head disappeared, and the erup- 
 tions gradually subsided. The results were fairly good, but not 
 entirely satisfactory. Gilbert and Foumier then resorted to goata 
 and dogs, into which they injected syphilitic, blood in doses of from 
 170 to 180 grams, or else they introduced beneath the skin of the 
 animals indurated chancres, papuke, and, simultaneously, blood. 
 The so rum obtained from these animals served to treat seventeen 
 patients. In a few cases the general state was ameliorated and the 
 strength increased, but in several other cases the method completely 
 failed. As the authors remarked, it is conceivable that there Bhould 
 be hesitation of judgment in the presence of such contradictory facts. 
 From the perusal of published observations it seems that the serum 
 derived from normal as well as from prepared animals may favorably 
 modify the general state of the patients, stimulate the reactions of 
 the organism, and favor cicatrization of atonic lesions. These results 
 point out the indications of the method. In a general manner, how- 
 ever, serumtherapy is considerably inferior to the classical treat- 
 ment. A similar conclusion is arrived at by Neumann, who reported 
 a few hardly satisfactory attempts. 
 
 Prophylactic Injections of Serum. Prophylaxis or, if the author may 
 say so, vaccination by serums, is superior to vaccination by attenu- 
 ated microbes or soluble products, because it exerts an immediate 
 action and does not cause the organism to pass through a prepara- 
 tory phase during which its resistance is diminished. On the other 
 hand, it is inferior, because the immunity which it confers does not 
 last long; it is effective only for a few days or weeks. It may. there- 
 fore, be theoretically stated that it is useful to vaccinate individuals 
 by means of attenuated or sterilized cultures in the presence of an 
 epidemic or in view of a future contamination; but we must resort 
 to the serum in case of urgency, especially when we fear that the 
 subject may already have been contaminated. Prophylactic injec- 
 tions of serum have been employed in several circumstances, notably 
 in puerperal women, in wounded individuals, and in those for whom 
 the development of tetanus is feared: finally and particularly, in 
 those who have been exposed to contamination by diphtheria. The 
 
 47 
 
738 LXEECTIOVS DISEASES. 
 
 observations regarding diphtheria cases are sufficiently numerous to 
 support a conclusion. 
 
 Roux is decidedly in favor of preventive injections. Behring is 
 of the same opinion. He advises the introduction of a small amount 
 of serum — 1 c.cm. of the Xo. 1 — and renewal of the injections every 
 six weeks. ' Unfortunately, this practise does not seem to be suffi- 
 cient. The amount administered is too small to obtain durable 
 immunity. In order not to overload our work with statistics, we 
 shall be contented with citing those given by Krasnobaeff. Out of 
 a total of 1965 individuals preventively injected, there were 43 cases 
 of diphtheria, three of which died. Considering the results obtained 
 in children's hospitals in various countries, it is found that out of 
 344 prophylactic injections there were 7 cases of diphtheria, 3 of 
 which proved fatal. 
 
 This gives a death-rate of 2.03 per cent. In these same hospi- 
 tals in non-injected children the mortality is about the same, 
 namely, 2.71 per hundred. 
 
 It would be an easy matter to report a very great number of cases 
 in which prophylactic injections have failed to prevent either the 
 development of the disease or a fatal termination. They do not, 
 therefore, seem to be very efficacious. Their employment might, 
 nevertheless, be recommended if the injections were absolutely harm- 
 less. Such is not the case, however, as we shall see in the following 
 chapter. And it is no wonder, then, that the prophylactic method does 
 not seem likely to become generally adopted. The author does not 
 believe that physicians, experimenters, or students connected with 
 diphtheria wards receive from time to time inoculations of the serum 
 as a preventive measure or give such injections to their families. 
 They are not to blame if they do not intervene before the disease is 
 manifested, because it is not wise to run the risk of the various serum- 
 therapy accidents with a view of avoiding an eventual contagion, 
 which is fortunately of very rare occurrence. Although it may be 
 resorted to under certain circumstances, for instance, when epidemics 
 attack a college or a ward of a hospital, or in families in which one 
 child has already died and the parents fear for the surviving children, 
 it does not seem that the method should be currently practised, for 
 there would be no reason for not regularly injecting in the near future 
 with various prophylactic serums with that of typhoid fever as well 
 as of erysipelas and pneumonia. It would be necessary to frequently 
 repeat these injections, since the immunity thus conferred is transi- 
 
THERAPEUTICS OF INFECTIOUS DI8EASE8. 7'.','.) 
 
 lory. This would tend to expose one's self to the vuriou accidents 
 of winch we are now about to speak. 
 
 Accidents Ascribable to Serumtherapy. We li:i \ <■ I hu. far reported 
 
 therapeutic attempts and results; we have studied the action of 
 serums regardless of the modifications and accidents which may be 
 caused by their use. We must now consider this important question 
 which has given rise to s great Dumber of contradictory contri- 
 butions. In this connection we may vU'r to an excellenl resume^ 
 namely, the thesis written by Dr. Poix 1 upon our advice. I' 
 very complete monograph, from which we shall borrow a good many 
 facts. 
 
 Cutaneous Manifestations. Abscesses. Serum injections may pro- 
 duce abscesses. This is not, however, an accident due to the method. 
 It is at present well demonstrated that (he process is one due to 
 carelessness, to insufficient disinfection of the skin and instruments, 
 or to an alteration in the serum. Exception is to be made only with 
 regard to the antistreptococcic serum obtained from animals immun- 
 ized by means of living cultures. The living microbes may then be 
 found in the fluid. We have found such to be the case in several 
 instances and recognized that the streptococci had preserved a cer- 
 tain degree of virulence. On the other hand, numerous observati ons 
 made upon man prove that these injections may give rise to ab- 
 scesses, phlegmons, lymphangites, or erysipelas, which are at times 
 sufficiently grave to cause serious anxiety. It is not to be concluded, 
 however, that the antistreptococcic serum thus prepared is to be 
 abandoned. In order to avoid accidents, it suffices to take the blood 
 a longer period of time after the last injection of the culture or to 
 filter the serum through porcelain. These precautions are evidently 
 quite elementary, but they must not be overlooked when a product 
 is destined to be used in the treatment of patients. 
 
 Exanthemata. Exanthemata are far more important. They are not 
 like abscesses, due to defective preparation; they depend upon the 
 action of the serums themselves, and seem, therefore, to be unavoid- 
 able, as they are caused by normal serum as well as by various 
 medicinal serums. They generally make their appearance three or 
 four days after the injection; at times on the tenth or even twentieth 
 day. The age of the subject does not seem to exert any influence. 
 
 1 Poix. Recherches critiques et experimentales sur le scrum antidiphtenque (son 
 action sur l'organisme, ses accidents"!. These de Paris, June. 1S96. 
 
740 INFECTIOUS DISEASES. 
 
 and, what is more difficult to explain, the accidents are in nowise 
 related to the doses introduced; 1 c.cm. or 2 c.cm. may give rise to 
 grave phenomena, while 10 c.cm. or 20 c.cm. of the same sample may 
 be well borne. All seems to depend upon individual predisposition. 
 In certain cases the manifestations consist simply in the appearance 
 of various eruptions, such as urticaria or erythema. In other 
 instances there is, in addition, fever and arthropathies. Finally, in 
 certain rare instances, albuminuria, hemorrhages, gastrointestinal 
 disturbances, etc., appear after the eruption. 
 
 The frequency of serumtherapy eruptions varies greatly from one 
 time to another, which is partly due to the fact that all horses do 
 not furnish identical serums. There are some the sera of which almost 
 invariably cause eruptions, while others hardly ever produce any. 
 It seems that accidents are less frequent when the animals are sub- 
 mitted to fasting before blood-letting is practised. It may, never- 
 theless, be remarked that the eruptions appear in 14 per cent, of the 
 cases. This is the figure given by Dubreuilh, who reviewed 1946 
 observations. The same author ranges the various eruptions accord- 
 ing to their frequency in the following manner: urticaria in 156 
 observations; scarlatiniform erythema, 46; polymorphous erythe- 
 mata, 31: rubeoliform erythemata, 11. These eruptions generally 
 make their appearance from the fifth to the thirteenth day after the 
 injection. They quite frequently begin at the point of inoculation, 
 invade more or less the rest of the skin, but, in general, do not 
 involve the face. Urticaria, the most frequent eruption, presents 
 nothing peculiar in its evolution. It is benign and transitory. As 
 their name indicates, the rubeoliform eruptions have the aspect of 
 measles, with which they might be confounded if the skin only was 
 examined. At times pure, they may often be mixed with scarlatini- 
 form eruptions. The latter generally occupy the back, the flexor 
 surfaces of the extremities, more rarely the thorax, and almost never 
 the face. They are in many cases pruriginous, whether urticaria 
 coexists or not. As a result of these eruptions, there is usually a 
 slightly marked desquamation. 
 
 Under the name polymorphous erythemata authors have some- 
 times described eruptions characterized by mixture of several erup- 
 tive types, sometimes eruptions in which certain elements become 
 bullous. In some instances the eruption assumes a hemorrhagic 
 character (Mendel) or that of purpura (Moizard and Perregaux). The 
 cutaneous manifestations are generally transitory. They last from 
 
THERAPEUTICS OF INFECTIOUS DI8EA8E8. 711 
 
 three to six days, but relapses occur in a certain Dumber ol c 
 They are often attended by arthropathie , 
 
 Arthropathies. Post-serumtherapy arthropathies are Bimply char- 
 acterized by particular pains, in most cai -<•.-■ coincident ••■ ith eruptions, 
 and never ending in suppuration. The only ob ervation of Buppur- 
 ated arthritis, that of Broca, is so complex thai it cannol with 
 tainty be attributed to the serum injected. The articular gymptonu 
 usually occur in the knee joint and ankle-joint, and are often attended 
 by muscular pain or neuralgia, at times by edema in the back of the 
 hands and feet. These arthropathies commonly disappear with the 
 eruptions. 
 
 General state. Beside the eruptions and articular phenomena, the 
 patient also presents a number of general manifestations. Fever 
 occurs and sometimes reaches 104° and even 105.8° V. (40° to 
 41° C). There 1 are digestive and urinary disturbances. These mani- 
 festations last but a few days, but the patient remains pale and tired. 
 In some cases, however, the disorders may last for several v 
 We must now consider in a special manner two scries of phenomena 
 which may occur separately: hyperthermia and urinary disorders. 
 
 Fever. Dr. Variot was the first to call at tent ion to the fever caused 
 by the injection of serums. He proved its existence by comparing 
 a great number of fever charts. We are able to confirm his obser- 
 vations on this point, for patients who arrive at our hospital ward 
 devoted to adults are generally apyretic. It is, therefore, very easy 
 to observe in them the occurrence of hyperthermia and to refer it 
 to its true cause. The febrile movement, which is often of a slight 
 and transitory character, may also be observed when serum is 
 injected as a prophylactic into normal subjects. The temperature 
 rises a few tenths of a degree or even two degrees. At the same time 
 the pulse is accelerated and sometimes becomes a little irregular. 
 These thermal elevations, which occur a few hours, sometimes a day 
 or two, after the injection of the serum, are not to be wondered at. 
 The same phenomena occur in consequence of injections of normal 
 serum. This fact has been observed in man as well as in animals. 
 The hyperthermizing action of normal serum had been noted by 
 ourselves, then by Drs. Mairet and Bosc: but we had practised intra- 
 venous injections. Poix made a very careful comparative study by 
 injecting normal as well as antidiphtheritic serum into rabbits. 
 These injections were made beneath the skin, and in both cases gave 
 rise to very decided hyperthermia. 
 
742 ' NFECTIO US DISEASES. 
 
 Modifications of the Urine. Injections of serum seem to modify 
 in a variable maimer the quantity of urine voided. Some authors 
 have noted a considerable diminution, others an increase, still others 
 no change at all. These contradictory results probably depend upon 
 the state of the individual under observation. What seem to be 
 more important are the qualitative modifications of the urine. 
 
 The serum causes an increase in the excretion of urea (Mya, Mon- 
 gour, etc.). Hyperazoturia generally lasts twenty-four hours; then 
 the amount of urea diminishes and returns to the normal. At the 
 same time there is a notable increase of phosphates and a slight 
 diminution of chlorides. Karlinski, experimenting upon himself, 
 found that a subcutaneous injection of 10 c.cm. produced no fever 
 and no urinary modifications. This dose, however, is rather too 
 small for an adult. By injecting larger amounts he noticed the 
 appearance of urticaria and an increase in urea, uric acid, and crea- 
 tinin. These urinary modifications lasted three days, but they did 
 not depend upon the antitoxin, since the author observed analogous 
 disorders with the serum of a normal goat. 
 
 Investigations pursued upon animals fully confirm the results 
 obtained in man. Our experiments 1 and those of Poix prove that 
 injections of serum produce slight polyuria, an increase in urea and 
 phosphates, and a diminution in chlorides. It is to be noted, how- 
 ever, that Poix has perfectly demonstrated that these various 
 modifications are likewise produced under the influence of normal 
 serum. 
 
 All that remains to say concerning the usual modifications of 
 the urinary secretion is that, according to Heckel, peptonuria is 
 constantly observed, and that, according to Le Genclre, urobilinuria 
 may be observed. It now remains to examine with particular atten- 
 tion a more serious accident with regard to which there is no general 
 agreement. We refer to albuminuria. 
 
 Albuminuria, Nephritis. The most varied opinions have been 
 advanced concerning the disturbances which the serum engenders 
 in the kidneys. As a matter of fact, clinical observations are always 
 very complex, and it is evidently quite difficult to determine the 
 role which is to be respectively attributed to the principal infection 
 and to the secondary infections in addition to those produced by 
 the serum. Some authors have, therefore, thought, and with good 
 
 1 Charrin and Roger. Action du serum antidiphterique sur la nutrition. Soc. med. 
 des hopitaux, December 14, 1S95. 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 743 
 
 reason, fchat it was necessary to study the question by experimenta- 
 tion upon animals. Unfortunately, the results obtained have been 
 quite contradictory. Vissman found that the kidneys were con- 
 gested, and he discovered by microscopic examination thai the 
 vessels were overloaded with blood and the cells of the tubuli filled 
 with refractive granulations. The histological examinations, how- 
 ever, were made upon fresh (issues, because the author believed 
 that reagents would prevent him from seeing the le ions. In the 
 experiments of Kossorotoff the alterations were more marked. 
 There was hyperemia, in (he liver and kidneys, and cloudy and 
 granular degeneraJ ion of I he cells. The results obtained by Von 
 
 Kahlden were al(oge(her diflerenl. A rahhil received 16 C.cm. in 
 
 four days; a guinea-pig received, in the same period of time, 12 c.cm. 
 Microscopic examination revealed no lesion in the kidneys and 
 myocardium. Nor did Zagari and Calabrese observe any renal 
 lesions in the animals which had received serum. Poix injected 
 into rabbits from 5 to 15 c.cm. of antidiphtheritic serum; two 
 animals received 25 c.cm. in three doses. Histological examinai ion, 
 made by Dr. Comte, revealed no appreciable alteration. 
 
 It seems, therefore, that the serum injected into rabbits and 
 guinea-pigs produces no renal alterations. This result evidently has 
 considerable value, but its importance should not be exaggerated. 
 It must not be concluded that the serum is incapable of producing 
 any alterations in man, since animals possess, in this respect, far 
 greater resistance. All experimenters who have attempted to create 
 nephritis or albuminuria in animals know how difficult it is to 
 succeed if brutal measures are not resorted to ; they also are aware 
 with what facility the manifestations subside and disappear. On 
 the other hand, it should not be overlooked that different animals 
 react differently against various serums. It seems, for example, 
 that the rabbit is far more sensitive than man to bovine serum; 
 it may, however, be the reverse with regard to horse serum. Let 
 us now see what occurs in man. Martin and Chaillou think that 
 the serum hinders the action of the toxin upon the kidneys and 
 considerably diminishes albuminuria. This conclusion may be 
 admitted with certain reservation. It is possible that the serum, 
 when injected at the beginning of the infection, by arresting the 
 toxi-infectious process, prevents the ulterior alteration of the kidneys ; 
 its action is like that of salicylate of soda, which, by opposing the 
 evolution of acute articular rheumatism, diminishes the frequency 
 
744 INFECTIOUS DISEASES. 
 
 of endocarditis. This, however, is only a theoretical deduction or 
 conception, since accurate information on this subject is lacking. 
 
 When albuminuria exists the serum does not seem to ameliorate 
 it. It is not strange that such should be the case. The serum is 
 no more capable of curing a renal lesion than salicylate of soda is 
 of curing rheumatic endocarditis. The anatomical alteration, when 
 once established, continues its evolution; the serum is capable only 
 of preventing its development. Some authors, however, go further 
 and accuse the serum of aggravaitng pre-existing lesions, a question 
 very difficult of solution. It is evidently necessary to resort to 
 experimentation to determine the result of the injections of serum 
 into animals in which renal alteration has previously been created. 
 This question was investigated by Ritter, who noticed that the 
 serum, when injected into animals recovering from artificial albumin- 
 uria, causes reappearance of albumin in the urine. On the other 
 hand, Zagari and Calabrese injected serum into individuals suffer- 
 ing from chronic nephritis, and did not observe any increase in 
 albuminuria. The question, therefore, requires more thorough study. 
 
 There remains a last group of cases in which the serum seems 
 surely to cause albuminuria. Such is the case when remote post- 
 serumtherapy symptoms supervene. Several days after the injection 
 of the serum, when eruptions, articular symptoms, and febrile 
 movement occur, albuminuria also may be observed. In this instance 
 it is quite difficult not to attribute the urinary disorder to the 
 influence of the serum; for, in cases of diphtheria treated by the 
 usual procedures, albuminuria seldom makes its appearance so 
 tardily. On the other hand, the symptom forms part of a whole 
 series of disturbances constituting a sort of clinical entity; there is 
 no reason for separating it from the rest. In most cases, these 
 albuminurias are transitory. In some instances, however, they 
 have proved quite serious. Elsewhere, the renal disorder has been 
 expressed by anuria, and in other cases by a hemorrhagic nephritis. 
 The latter manifestation seems to us interesting because, in the 
 genesis of post-serumtherapy accidents, hemorrhages play an im- 
 portant role. Experimenters had already observed multiple hemor- 
 rhages in consequence of the introduction of foreign blood or serum 
 into animals. 
 
 Hemorrhages. Besides hemorrhagic nephritis and cutaneous 
 hemorrhages, notably purpura, the serum has sometimes given rise 
 to epistaxis and uterine hemorrhages. D'Astros made a careful 
 
TllKltAl'KUTKJS OF TNFE0TI0U8 DISEASES. 745 
 
 study of tin; action of serum upon the uterine functions, and found 
 that when it is applied at the time of men truation i\ increase the 
 flow; during the interval it brings h on. Metrorrhagia appean the 
 day following the injection, or later, li generally coexists with ■*' 
 cutaneous eruption. However, in a case in which the erum 
 injected into a pregnant woman, the progre o] pregnancy wai in 
 nowise disturbed. 
 
 Modifications in the Blood. It is difficull i" Bay whether hemor- 
 rhages following serumtherapy resu.l1 from an action exercised upon 
 the vasomotors or upon the blood itself, h is known thai the serum 
 produces some interesting modifications in the constitution of the 
 blood. It diminishes leucocytosis. This is tiol a common action 
 engendered by any serum whatever. The researches of Ewing 
 clearly deinonstrated (hat il is due to a specific action of the anti- 
 toxin. He proved it by experiments upon animals and observations 
 in man. Hypoleucocytosis lasts twenty-four to forty-eight hours. 
 It is especially the mononuclears and, among the polynuclears, those 
 that are stained with difficulty, that disappear. The poly nuclear 
 cells that are well stained do not present any modifications. I' is 
 probably a process of negative chemiotaxis, which causes such an 
 accumulation of leucocytes in the viscera that it has been questioned 
 whether it is not dangerous. 
 
 Another interesting phenomenon is the fact that the serum 
 increases the aptitude of the leucocytes for taking up dyes. Toxins 
 have a reverse effect. In those cases in which the injection of serum 
 does not cause the reappearance of a normal tinctorial reaction in 
 the leucocytes, prognosis may be considered as fatal. If these facts 
 were confirmed they would constitute a very simple means of fore- 
 telling the evolution of diphtheria. For the time being we must be 
 contented with the fact that the number of leucocytes undergoes 
 variations. On this point the investigations of Schlesinger have 
 confirmed those of Ewing: Out of twenty-four children suffering 
 from diphtheria, in twenty-one the injection of serum first caused 
 leucocytosis to disappear; this was followed by a slight secondary 
 leucocytosis. 
 
 These results are evidently interesting in view of the important 
 role which the leucocytes plav in the protection of the organism. 
 It is for this reason that authors have devoted special attention to 
 wandering cells. It is to be regretted, however, that they have 
 neglected the red globules. The question was taken up only by 
 
746 ISFECTIO US DISEASES. 
 
 Zaggari and Calabrese, who observed a diminution in the number of 
 
 red corpuscles and of their richness in hemoglobin. These researches 
 are particularly welcome for the reason that serum has been held 
 responsible for some grave and rebellious anemic conditions. Chil- 
 dren who had received it as a preventive are said to have for months 
 remained pale, weak, and to have presented furuncular eruptions, 
 which means a marked disturbance in their nutrition and develop- 
 ment. This conclusion finds support in Dr. Arloing's investigations. 
 This author studied the development of young guinea-pigs into 
 which he daily injected small amounts of normal or antidiphtheritic 
 serum. "While the controls increased 34 per cent, of their initial 
 weight, the animals which received normal as well as immunizing 
 serum increased only 19 or even 16 per cent. The foreign serum 
 thus exercises a harmful action, and the longer the serum is admin- 
 istered the more marked is this action. Of course, the quantities 
 introduced were relatively more considerable than in the case of 
 the child, but we know how resistant animals are. Without pro- 
 ducing such harmful results, they are bad enough if only nutrition 
 is disturbed and development hindered. 
 
 Other Accidents Ascribable to Serum. Other disorders attribut- 
 able to the use of the serum have been observed in the course of post- 
 serumtherapy syndrome, coincidently with eruptions and arthrop- 
 athies. These disturbances consist in vomiting, profuse diarrhea, 
 sometimes dysinteriform and sanguinolent diarrhea, swelling of the 
 lymphatic glands and spleen, and, finally, cardiac disorders. The 
 latter seem to be quite frequent, at least according to observations 
 published in foreign countries. 
 
 Baginsky, who later on changed his opinion, Hunnius, Schroeder, 
 and Springorum dwell upon cardiac arythmias, tachycardia, and 
 bruit de galop. They likewise noted edema of the extremities, 
 which indicates considerable weakness of the heart, and reported 
 observations in which these various disturbances were quite serious 
 and alarming. In a case concerning a young woman twenty years 
 of age we observed some interesting nervous manifestations. In 
 taking care of a three-year-old child suffering from diphtheria she 
 had been bitten by the child and received two small abrasions on 
 her middle finger. On the following day, the physician fearing the 
 development of cutaneous diphtheria, hastened to inject 40 c.cm. 
 of serum into the young woman, and sent her to our hospital. The 
 wounds presented a good appearance and seemed in nowise diph- 
 
THERAPEUTICS OF TNFE0TI0U8 DISEASES. 7 17 
 
 theritic. For greater safety, however, culture were made, which 
 demonstrated the presence of no other microbes than the staphylo- 
 coccus albus. Eight days later the symptomi of serum intoxication 
 appeared, with fever progressively attaining 100.4° and 102.2° I 
 (38° and 39° C.) and articular pains. Two days after, this woman had, 
 for the first time in her life, a well characterized attacl teria. 
 
 From that moment on a series of neurotic manife tatione appeared. 
 First, convulsive attacks which recurred for three days in succe rion; 
 then the patient became indifferenl to everything aboul her, hardly 
 replying to questions. The temperature oscillated around loi I . 
 (40° C), and pulse 120 per minute; the tongue was dry. A few 
 days later she suffered from anuria for forty-eighl hours; then she 
 had mutism for two days; after that the patient fell into an ecstatic 
 state which lasted for a week. A month after the beginning of the 
 disturbances she recovered. 
 
 It might be supposed that in this observation the question 
 one of traumatic hysteria, excited by the biting. The appearanre 
 of nervous symptoms forty-eight hours after the beginning of the 
 fever caused by the serum, however, seems to indicate that it was 
 a case of toxic hysteria and that the injection of the serum had 
 been the cause of the manifestations. 
 
 Prognosis of Serumtherapy Accidents. We have above described 
 the phenomena which may be attributed to serumtherapy. These 
 unfavorable symptoms have been observed mostly in consequence 
 of the use of antidiphtheritic serum. This is due simply to the fact 
 that this serum is the only one currently employed, since it seems 
 to be well demonstrated that the majority of these phenomena 
 are not due to the antitoxin, but to an action possessed by all 
 foreign serums. 
 
 An injection of serum almost always gives rise to a reaction, such 
 as transitory elevation in the temperature, which, in most cases, 
 hardly deserves the name accident. This reaction, however, may 
 acquire alarming intensity in certain subjects who are already sick. 
 This may occur notably in tubercular patients. Roux and Yariot 
 agree that the serum does not produce good results in this disease : 
 it produces certain disturbances, and such is the opinion of several 
 authorities. The injection of serum gives rise to a congestion just 
 like an injection of tuberculin. In several personal cases, one of 
 which was reported in Poix's thesis, we found that the injection 
 of 20 c.cm. of serum caused a notable elevation in the temperature 
 
748 ISFECTIO US DISEASES. 
 
 and aggravated the general state of the patient. In the case pub- 
 lished by Poix the patient died seven days later, and the necropsy 
 revealed advanced tubercular lesions. It is difficult to say what 
 the respective role of tuberculosis, of diphtheria, and of the serum 
 had been in this fatal termination. "We believe, however, that in 
 cases of tuberculosis, at least of adults whose lesions are well pro- 
 nounced, it is necessary, if diphtheria is not too grave, to abstain 
 from injecting serum and have recourse to simple local treatment. 
 
 Barring this particular case, truly serious accidents are those 
 which constitute the tardy syndrome. While in most cases the 
 phenomena are transitory and in nowise disquieting, they at times 
 last for four and five weeks. In other instances terrible manifesta- 
 tions, such as anuria and collapse, have been observed (Thibierge). 
 It is true, however, that except in a few cases the patients have 
 generally recovered. 
 
 "We here arrive at a much disputed problem. May death result 
 from serumtherapy? We may recall the communication of Moizard 
 and H. Bouchard 1 and the bitter discussion to which it gave rise. 
 Guinon and Rouffilange 2 published an analogous case, and others 
 may easily be found in foreign literature. It is true that several 
 of these cases cannot bear criticism; such is notably the strange 
 observation of Langerhans' boy. There are others, however, which 
 cannot be easily explained away. One such interesting case is that 
 related by Izor Alfolcli: Forty-eight hours after an injection of 
 2 c.cm. of Behring's serum No. 1, administered as prophylactic, 
 a three-year-old child developed fever. The temperature rose to 
 104° F. (40° C.) attended by lumbar pains and much albuminuria. 
 On the third clay the child had nausea, an eruption of petechia on 
 the body, and died the fourth day. The mechanism of these pheno- 
 mena is open to discussion, but it is hardly possible not to admit 
 a relation of cause and effect in the fact of so typical a syndrome 
 appearing a few days after an injection of the serum in a child 
 which until then was perfectly healthy. It seems to me that nothing 
 is gained by systematically explaining away such observations or 
 interpreting them in such a manner as to clear serumtherapy of 
 
 1 Moizard and Bouchard. Un cas d'angine non-diphterique, traits par le serum, suivi 
 de mort. Societ6 medicale des hopitaux, July 5, 1895. 
 
 2 Guinon and Rouffilange. Un cas d'angine membraneuse traite par le serum de 
 Roux; mort avec anurie et convulsions uremiques. Revue mens, des maladies de 
 l'enfance, March, 1895. 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 7l!> 
 
 all responsibility, [t Is better bo acknowledge frankly thai erum 
 may produce some accidents. At all events, whal medicine i 
 be considered perfectly harmless? Is there any active ufa tance, 
 even chemically well defined, which never occa ion any disturb- 
 ances? Only those who endeavor forcibly to tran fer mathematical 
 data into the domain of biology can imagine thai il i- po rible to 
 fix immutable doses and establish a formula in which dang< 
 and fatal doses will be precisely indicated. In reality, facte are 
 more complex. The experimenter himself musl take into account 
 the individual peculiarities of animals. As regards serum particu- 
 larly, individuals of the same race, age, and weigh! read very 
 differently against the same fluid. The investigations of Bayem, 
 Mairet, Bosc, and of ourselves, demonstrated this fact beyond all 
 dispute. The same is undoubtedly (rue of man, whose idiosyncrasies 
 are far more marked. In proportion as the nervous functions are 
 more perfected and complicated the results become less and less 
 fixed, while sensitiveness to toxic agents becomes more and more 
 pronounced. 1 
 
 We should say that the disturbances, at any rate exceptional, 
 which may occur in consequence of serum injections, must by no 
 means restrict the employment of the method, but impel experi- 
 menters and clinicians to perfect it. Since most of the dangerous 
 phenomena are due to the serums, and are independent of the 
 antitoxin, the efforts of experimenters should be directed to the 
 preparation and isolation of the active substance. The day when 
 we possess a product which, if not pure, is at least freed from a 
 great number of useless or harmful substances, decided progress 
 will have been accomplished. Meanwhile, we are fortunate to 
 possess a therapeutic method which has notably reduced the death- 
 rate. 
 
 Causes and Mechanism of the Accidents. It is impossible to 
 argue to-day that the disturbances following serumtherapy are due 
 to diphtheria itself, or that they are produced only after such grave 
 cases of diphtheria which, without the new treatment, would termi- 
 nate in death. The appearance of similar manifestations in healthy 
 subjects who have received preventive injections, or in persons 
 suffering from non-diphtheritic anginas, suffices to invalidate this 
 
 1 There will be found a number of facts demonstrating individual sensibility to toxic 
 agent in the author's article. '• Intoxications." Traite de pathologie generate, Paris, 1S95, 
 vol. i. p. S49. 
 
750 INFECTIOUS DISEASES. 
 
 explanation. On the other hand, identical disturbances, not only 
 eruptions, but articular symptoms, fever, gastric disorders, and 
 hemorrhages occur in consequence of injections of normal serums. 
 It is not, therefore, the antitoxin that is responsible for the disorders 
 but the introduction of a foreign serum. 
 
 It cannot- be objected that nothing of the kind occurs when the 
 blood of horses is injected into rabbits, for it is possible, with other 
 serums, to obtain results comparable to those occurring in man. 
 If the blood of dogs is introduced into rabbits, albuminuria and 
 hemorrhages often appear. The results are still more interesting 
 when cow's serum is injected into dogs. According to Dr. Hayem, 
 considerable individual differences, resistances altogether dissimilar 
 from one individual to another, are observed. The same injection 
 may produce nothing in one dog and cause in another, apparently 
 identical with the first, hemorrhages, anuria, or albuminuria, and 
 even death. This is, therefore, as far as is possible in experimentation, 
 the reproduction of what occurs in clinical experience. 
 
 These facts will serve to refute a very ingenious theory advanced 
 by Sevestre. 1 This able clinician divides serumtherapy disturbances 
 into three groups: Those immediately following the injection of 
 the serum, viz., elevation in the temperature and acceleration 
 of the pulse — accidents which, like the preceding ones, are due to 
 the serum. Such is flying urticaria, appearing from the fourth to 
 the sixth day. Finally, the tardy disturbances, namely, those of 
 a serious character, including various exanthemata, albuminuria and 
 articular disorders. Regarding these Sevestre does not admit 
 that they are due to the action of the serum, but he attributes 
 them to the influence of streptococci, viz., to secondary infections. 
 His theory has not manj^ adherents. It seems to me hardly 
 acceptable, for, as it has already been stated, the serum causes the 
 same disturbances in individuals suffering from chronic infections, 
 and in normal subjects. All that may be admitted is that by dis- 
 turbing the organism the serum may favor the development of 
 microbes until then inoffensive. It may also be admitted that 
 certain symptoms are of an infectious order. For instance, dysenteri- 
 form diarrheas may be due to exaltation of intestinal bacteria. 
 Analogous symptoms are observed in the course of a great number 
 of intoxications. A well-known instance is mercurial stomatitis or 
 
 1 Sevestre. Des accidents imputables a la s'rumtherapie ou au streptocoque dans 
 la diphterie. Soc. med. des hopitaux, July 19, 1S95. 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 7r,\ 
 
 enteritis. The microbes of the mouth and of the inte tine c 
 these lesions, but their action is rendered possible through the 
 intervention of mercury. Mercurial stomatiti and enteritis musl 
 remain among toxic affections, and the same i true of po I 'ruin 
 therapy accidents. 
 
 Among the substances contained in the serum, i1 is the albumins 
 that are probably the active agents. The numerous experimental 
 investigations which have shown the dangers of heterogenous trans- 
 fusions have demonstrated thai all the disturbances depend upon 
 albuminoid matters. On the other hand, the research© of Mairel 
 and Bosc proved that heating the serum between 132.8° and L38.2 I . 
 (56° and 59° C.) may abolish its coagulating and globulicidal prop- 
 erties, but its toxic action remains intact. Therefore, the blood 
 docs not produce disturbances by destroying the globules of the 
 transfused individual or by causing coagulation in the vessels. 
 
 For the time being we are unable to further elucidate I he mechan- 
 ism of the phenomena. We do not know whether the direct action 
 of the foreign albumin or that of the products resulting from its 
 decomposition are responsible, or whether we must admit the 
 secondary formation of noxious products within the organism. 
 
 Mode of Action of Therapeutic Serums. After all the develop- 
 ments above presented regarding the chemical modifications occur- 
 ring in vaccinated animals and concerning the special characters of 
 their serums, the mode of action of the latter will be briefly con- 
 sidered. 
 
 Two principal theories have been advanced: One of them 
 endeavors to reconcile the results of serumtherapy with the ex- 
 clusively phagocytic doctrine; the other seeks for a purely humoral 
 explanation. In the first place, it is supposed that therapeutic 
 serums act by stimulating the activity of the wandering cells and 
 by increasing their phagocytic power. If. in certain instances, the 
 serum acts more energetically when injected into the adjacent parts 
 of a local lesion, this is due to the fact that it exercises a positive 
 chemotaetic action; it calls out, so to say. and attracts the leuco- 
 cytes to the point threatened. The active substance would then 
 deserve the name stimuli n. 
 
 Several objections could be raised against this hypothesis. By 
 means of very ingenious experiments, Denys and Leclef demon- 
 strated that, in rabbits vaccinated against the streptococcus, the 
 leucocytes are not more active and aggressive than in normal rabbits. 
 
752 INFECTIOUS DISEASES. 
 
 Whether or not the animals are refractor)-, the leucocytes do not 
 attack the virulent microbes; they seize only those which have been 
 altered by the curative serum. These researches bring us to the 
 theory which we have always advocated, viz., that immunity is the 
 result of the co-operation of two principal factors: the plasma or the 
 scrum, which temporarily weakens the microbe, and the leucocyte, 
 which picks up and destroys it. Were it not for the previous action 
 of the fluids the phagocytes would be powerless and the infection 
 would develop, and without the terminal action of the phagocytes 
 the microbes, which were temporarily weakened, would finally prove 
 victorious, as they do in vitro ; the infection would be delayed but 
 not arrested. 
 
 Let us apply these data to serumtherapy. By injecting the 
 prophylactic or curative serum, we assist an organism which secretes 
 antibacterial or antitoxic substances ; since from the very beginning 
 of the infection, or at least in some cases, the organism reacts against 
 the microbe and endeavors to oppose it by substances which hinder 
 its development. This protective secretion may be insufficient or 
 tardy. We then come to the assistance of the struggling economy 
 by furnishing it with substances formed in another organism. If 
 the animal furnishing the blood is endowed with an immunity just 
 sufficient for itself, its fluids will prove to be of moderate activity 
 and the result will be almost negative. If, on the contrary, the 
 animal is hypervaccinated, its fluids will contain an excess of pro- 
 tective substances, and the small amount injected will contain a 
 sufficient quantity of antibacterial or antitoxic matters to favorably 
 modify the morbid evolution. 
 
 Serumtherapy is, therefore, nothing else than a variety of anti- 
 septic or antidotal medication. In the case of an antibacterial 
 serum, serumtherapy introduces into the organism a specific anti- 
 septic which hinders the vegetation and activity of the microbe. 
 When the serum is antitoxic it introduces a substance which affects 
 the cells of the patient, increases their resistance or prevents their 
 impregnation. While the theory of stimulins may be comprehended 
 when we consider the struggle against living bacteria, it is no longer 
 intelligible when we consider the antitoxic role of serums. In fact, 
 the experiments of Chatenay and Metchnikoff demonstrate that the 
 number of the leucocytes diminishes when the animal succumbs to 
 an intoxication, and that it increases if the animal is vaccinated and 
 rendered resistant. Must it be concluded that, in the latter instance, 
 
THERAPEUTICS OF INFECTIOUS DISEASES. ::,.; 
 
 the leucocytes pick up the toxic ubstance , and must we thus 
 extend to all the poisons the theory which ome authoi endi 
 to establish concerning peptone? Such conclu ion eem to be 
 premature. To deduce such an importanl action from the imple 
 fact that the leucocytes increase in number when a toxic ubstance 
 is injected into a refractory animal seems to u to make too much 
 of such a result. Before admitting or rejecting the hypothe i 
 must demand experimental facts, and especially a careful demon- 
 stration of the r61e played by the antitoxic function* of organs in 
 vaccinated animals. Serums have such an importanl pecific action 
 that no one has given any attention to the other effects which they 
 may produce in the organism. In order to completely appreciate 
 their mode of action and explain certain cases in which a serum 
 has acted against an infection of another nature, it must be re- 
 membered that the normal serum or even saline solutions may very 
 favorably modify the course of various infectious or non-infectious 
 diseases. We have already stated that the serum of certain animals 
 is capable of favoring cicatrization of the most varied ulcerated 
 lesions, notably syphilitic and tubercular lesions. Reinach tried in 
 cholera infantum the serum of cows or horses, of which he injected 
 from 10 to 20 c.cm. Out of twenty-five children thus treated only 
 four died, and these suffered from pneumonia. In consequence 
 of the injection, the pulse improved, cyanosis disappeared, and the 
 extremities became warm. These good results are probably due. 
 at least in part, to the nutritive value of the serum. According to 
 this author, 20 c.cm. of serum correspond to 150 grams of mother's 
 milk. It may be asked, however, whether the serum of animals, 
 like saline solutions, does not exert an indirect action upon infections 
 by modifying the state of the nervous system. The results obtained 
 in the treatment of neurasthenia and the modifications produced 
 in the arterial tension give a certain value to this hypothesis. These 
 secondary influences may, of course, be ignored when we consider 
 the action of specific serums. They are interesting only when we 
 look for an explanation of the favorable effects obtained with such 
 serums as are of moderate activity or which are obtained from 
 normal animals. 
 
 Conclusions. In spite of the numerous investigations to which 
 serumtherapy has given rise, we must acknowledge that it has not 
 given undeniable practical results except in diphtheria. Even in 
 this instance its efficacy is not so great in man as would be expected 
 
 48 
 
75-1 INFECTIOUS DISEASES. 
 
 from experiments pursued upon animals. The same remark is appli- 
 cable with more force to other serums, all of which are capable of 
 saving laboratory animals experimented upon and so often fail when 
 tried on patients. This divergence between clinical and experimental 
 results may readily be explained. The animals upon which experi- 
 ments are pursued have been made ill by artificial means. Conse- 
 quently, they were in a state of perfect health and in nowise disposed 
 to be invaded by the infection. It was necessary to overcome their 
 resistance brutally, and this unexpected arrival of microbes aroused 
 immediately a prompt and vigorous reaction on the part of the 
 organism invaded. On the other hand, the artificial disease is simpler, 
 since it remains for a long time monomicrobic. Lastly, the treatment 
 is applied in due time. A few hours, one day at the latest, after the 
 inoculation intervention takes place in the first stage or even during 
 the stage of incubation, while no morbid symptom has as yet ex- 
 pressed or revealed the invasion of the organism. In the case of 
 man, however, the situation is altogether different. Except in rare 
 instances, infection is not inoculated. Even in cases of traumatism 
 the microbes are introduced in too small numbers to admit compari- 
 son with what occurs in the laboratory. If, therefore, disease is 
 produced, it is due to a morbid predisposition, a previously debili- 
 tated state of the organism; its resistance was not artificially over- 
 come in a brutal manner, but was progressively reduced by a series 
 of preparatory conditions. Hence, when the microbe penetrates, 
 reaction does not occur immediately, and is often incomplete or 
 insufficient. On the other hand, the disorders which have prepared 
 the development of the infection or the previous diseases, of which 
 no apparent traces are presented by the subject at the moment of 
 the attack, may have produced more or less profound visceral lesions 
 which added their unfavorable influence to that of the infectious 
 agents. Finally, the natural disease is not so simple as the artificial, 
 for it is seldom monomicrobic. Several bacteria are almost always 
 called into play, and thus modify the clinical course and increase the 
 complexity of each case. 
 
 Hence, when we intervene by the serumtherapy method we face 
 a disease dependent upon a series of various causes and the evolution 
 of which is advanced, for a whole period of incubation and of pro- 
 dromes has elapsed during which there has been no clear diagnosis 
 of the nature of the infection. When the symptoms are clear and 
 the diagnosis is established it may be too late to intervene. Such 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 
 
 is fche case in tetanus. It there ii yet time, the physician hesitate* 
 to apply aew methods, and thus there i a delay which sometimes 
 renders intervention useless. Let us uppose thai action hat been 
 taken indue time, from the beginning of the disorders, are wr< 
 of obtaining favorable results? Evidently not. The serum may 
 combat bacterial intoxication, it may oppose the development of the 
 microbes, it may neutralize their products of secretion, bul it can 
 accomplish nothing against concomitanl autointoxications. The 
 organs altered by previous diseases or by the present malady can 
 no longer fulfil their functions in transforming or eliminating the 
 toxins of cellular origin. ( )n I he ol her hand, it is to be remembered 
 that there is an exaggerated production of poisons resulting from 
 the nutritional disorders engendered by the disease. In view of 
 these facts it is impossible, even when infection is monomicrobic, to 
 draw conclusions from animal to man. Hence, serums succeed better 
 in laboratories than in clinical experience, and, for this reason, old 
 therapeutic methods should not be abandoned. 
 
 Under the influence of the enthusiasm which was aroused by anti- 
 diphtheritic serumtherapy, many believed that traditional thera- 
 peutics had served its time. Many believed thej^ perceived the dawn 
 of a new era when medicine would be simplified in a marvellous 
 manner: no more auscultation, no more examination of patients; it 
 would suffice to look for the pathogenic microbe and immediately 
 inject the corresponding serum. These ideas, which were sustained 
 by some eminent scientists, do not conform to the reality. To thus 
 exaggerate the value of even such a magnificent method tends to 
 bring it into discredit and to expose one's self to cruel disappoint- 
 ments. This medication of equation, to use an expression of Lan- 
 douzy, will not succeed in therapeutics any more than elsewhere. 
 Biological phenomena, especially pathological manifestations, are too 
 complex to be modified by simple and uniform procedures. Serum- 
 therapy is not destined to do away with the other methods. It must 
 simply be considered as a new means to be employed concurrently 
 with others. In the case, for instance, of a woman suffering from 
 puerperal fever, whatever may be our confidence in serumtherapy, 
 we should never resort to an exclusive method. We must continue to 
 practise curettage, intra-uterine irrigations, and prescribe cold baths, 
 being convinced that it is necessary to employ multiple measures of 
 various effects in order to combat multiple phenomena of various 
 origins. 
 
756 INFECTIOUS DISEASES. 
 
 AVhile we cannot say too much in approval of the efforts of those 
 pursuing researches upon specific serums, we must, in the interest of 
 clinical experience, protest against the exclusive employment of 
 laboratory methods. We have endeavored to show why a sick man 
 is not comparable to an inoculated animal. It is not sufficient to 
 combat the microbe, since, in this manner, post-infectious lesions 
 would be left free to follow their evolution and the patient would 
 succumb to autointoxication. 
 
 Although it is not safe to forecast the future, the author does not 
 believe that serumtherapy is destined to revolutionize, completely 
 the art of healing. The method has supplied a new means of defense 
 and success; it has enabled clinicians to reduce the death-rate and 
 triumph where they formerly failed. The results are already suffi- 
 ciently marvellous ; there is no need of exaggerating them or of dis- 
 crediting other methods. By the whole of reasoned procedures it is 
 possible to overcome complex symptoms. The indications of serum- 
 therapy should be determined, and it should be associated with 
 other methods. Such is the path which clinicians should follow. In 
 the meantime experimenters will perfect the methods. They will 
 succeed in purifying the antitoxins and freeing them from useless or 
 harmful substances accompanying them. This is the imminent dis- 
 covery. When it is achieved, a new advance will have been made 
 in serumtherapy, a new result acquired for the consolation of 
 humanity. 
 
CM A PT E R XXIII. 
 THERAPEUTICS OF [NFECTIOUS DISEASES {Concluded). 
 
 Physiological Medication, Method De Lgned to In <"<■ <!"■ Function of I 
 Protective R61e <>f the Liver. Importance of AJimenl and ->f Cold Enem 
 oation by Ether. Protective Rdle of the Lung; Rdle of the Blood. Oxidizing 
 Method. Rdle of the Emunctories. Sialogogues; Diuretic ;Expectoran1 ;Emei 
 
 Purgatives. Treatment of [nfli atorj Manifi tation Local Treatment. II" - 
 
 Applications. Refrigeration, [mmobilization and Compre ion. Depletion. Re- 
 vulsion. Indications and Mechanism ol Revul Lon. Vasomotor Medication 
 Treatment of Serous, Purulent, and L'seudomembranou Exudates, oi Qangrenoui 
 and Nodular Lesions. Treatmenl of Hemorrhages. Chloride of Calcium. \ 
 constrictors. Astringents. Gelatin. Treatmenl of Fever. < <>1.1 and Hoi Ba 
 Brand's Method. Balneotherapy Rules for Typhoid Fever, Scarlatina, Variola, 
 Pneumonia, Bronchopneumonias, and Erysipelas. Chemical Antithermal Med- 
 icines. Blood-letting; Mode of Action and Indications. Injections of Artificial 
 Serum: Their Action on Absorption, on Renal Elimination, on the Nervous System, 
 and on Nutrition. Indications for Subcutaneous and Intravenous Injections of 
 Artificial Serum. Symptomatic Medication. Treatment of Nervous, Cardiac, and 
 Vascular Disturbances and Disorders of the Respiratory, Alimentary, and the 
 Urinary Apparatus. 
 
 Physiological Medication. 
 
 All the forms of medication we have thus far studied were directed 
 against the pathogenic agent. Their object was to destroy the invad- 
 ing microbes, hinder their development, and neutralize their toxins. 
 The antiseptic and antitoxic medications represent the two principal 
 methods which resume the endeavors made in this direction. Serum- 
 therapy particularly belongs to this group. It possesses a special 
 interest, because it constitutes a naturalistic method. By introduc- 
 ing a specific serum we accomplish sooner what the organism would 
 later. Investigations in pathological physiology teach us that during 
 infections certain organs endeavor to destroy microbes and neutralize 
 or eject poisons. Therefore, in the stud}' of the reactions of the 
 organism we may find important therapeutic indications. 
 
 The efforts of the physician must tend to assure the function of 
 the protective organs or promote their action. In all probability 
 most of the cells of the organism play a role in its protection. As 
 yet we are acquainted with but a small side of the question. We 
 know that the liver is capable of arresting and destroying certain 
 
758 IXFECTIOUS DISEASES. 
 
 microbes and toxins, and that the lungs act in the same way. We 
 know that poisons may be eliminated through secretions, and par- 
 ticularly through the renal secretions and accessorily by the secre- 
 tions of the digestive canal. Finally, we know that the fight against 
 microbes and then toxins in the interior of the organism is assured 
 by chemical modifications occurring in the plasma and by the par- 
 ticipation of a great number of wandering cells. These changes in the 
 fluids and cells are dependent upon increased activity of the hema- 
 topoietic organs — of the spleen, lymphatic glands, bone-marrow, and, 
 in young children, the thymus gland. 
 
 In spite of numerous studies pursued on this subject, the facts 
 are as yet imperfectly known. Nevertheless, certain among them 
 may already be taken as a starting point for some therapeutic indi- 
 cations. 
 
 Protective Role of the Liver. Among the organs playing an 
 important role in the protection of the organism against infections 
 the liver deserves to be placed at the head of the list. Some years 
 ago we demonstrated that this organ was capable of arresting and 
 neutralizing a variety of poisons of external origin or formed within 
 the diseased organism. More recent experiments enabled us to 
 affirm that this protective action extends to toxins, at least to some 
 of them, and to some microbes. Whether, however, the question is 
 one of soluble products or of figurate elements, the action of the liver 
 is not exercised unless the parenchyma contains glycogen. No mat- 
 ter whether this substance plays an active role in the phenomena of 
 defense, or whether it represents simply an evidence of cellular activ- 
 ity, the only interesting point is that, to a certain extent, it enables us 
 to measure the activity of the liver and determine with accuracy the 
 function of the gland. Knowing the conditions under which glycogen 
 is diminished or increased, we are able to lay down therapeutic indi- 
 cations calculated to maintain the protective activity of the liver. 
 
 It is often repeated that, for this purpose, it is indispensable to 
 combat hypothermia. Fever is said to cause the disappearance of 
 glycogen. This statement is exaggerated. When hyperthermia is 
 engendered by inoculation of an infectious microbe glycogen remains 
 intact during the febrile period and diminishes at the end of the 
 infection, at the time when the temperature falls below the normal. 
 Nevertheless, it is always advisable to combat excessive elevation of 
 temperature as well as hypothermia. It is here that the use of baths 
 is indicated — cold baths in the former instance, warm baths in the 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 759 
 
 latter. They re-establish the organic combu tiom and bring them to 
 the rate which is favorable for glycogenosis. 
 
 The second condition which modifie glycogen© i i of still greater 
 importance. We refer to starvation. Claude Bernard long 
 demonstrated that glycogenosis is diminished in animals deprived of 
 food. We have learned that, under the same conditions, the pro- 
 tective r61e of the liver againsl poisons and microbes i weakened. 
 These facts demonstrate thai it is indispensable to nourish infected 
 individuals. They are qo longer deprived of aliments, and are gener- 
 ally given milk, sometimes bouillon or oilier lighl nourishment. The 
 author believes that warm beverages containing sugar produce, from 
 this point of view, a very favorable effect. The sugar furnishes the 
 most important element for glycogenesis. The patienl should not. 
 therefore, be deprived of it. It would even be better, perhaps, to 
 utilize grape sugar instead of cane sugar. In fact, saccharose must 
 be converted before it can serve for the formation of glycogen and 
 the nutrition of the organism. We do not know whal the activity 
 of the invcrsive intestinal ferment in the course of diseases is. It 
 would, therefore, be preferable to employ glucose. In this connec- 
 tion honey seems to the author clearly indicated. As is known, it 
 contains from 65 to 75 per cent, of glucose and from 2 to 8 per cent. 
 of cane sugar. 
 
 In recent years an endeavor has been made to increase the alimen- 
 tation of patients suffering from fever. These attempts will be dis- 
 cussed in connection with general hygiene. It is certain, however, 
 that from the particular point of view occupying us the method i> 
 of incontestable advantage. The importance of certain elements for 
 the defense of the organism, notably carbohydrates, should not. how- 
 ever, be exaggerated. Experimental investigations pursued by us 
 demonstrated that while small amounts of glucose increase the 
 protective action of the liver large closes diminish it. The thera- 
 peutic amount of glucose may be said to be, at least for the rabbit, 
 3 grams per kilogram of animal, and 8 or 10 grams the unfavorable 
 amount. If these results were applied to man. from ISO to 200 grams 
 of glucose should be administered per day to an adult weighing 60 
 or 65 kilograms. 
 
 It is not only feeding that assures the function of the liver : thera- 
 peutics furnishes us a valuable agent — ether. As in the case of sugar, 
 however, the effects of ether vary with the amount administered. 
 In animals, 0.4 c.cm. of ether per kilogram of animal increases con- 
 
760 IXFECTIO US DISEASES. 
 
 siderably the action of the liver; 1 com. abolishes it. Subcutaneous 
 injection of ether produces a favorable action; but the best effects 
 are obtained by ingestion. In this case the substance passes directly 
 to the liver, and at the same time stimulates its glycogenic function 
 and its action upon toxins and microbes. The application of these 
 experimental data is very simple. When hepatic insufficiency or 
 torpidity is suspected, 20 or 30 grams of syrup of ether containing 
 2 per cent, of the active substance should be prescribed per day. 
 Stimulation of the liver may possibly be obtained by other medicines, 
 but no accurate data are as yet at hand bearing upon this point. 
 There is every reason, however, to suppose that purgatives and not- 
 ably calomel, and perhaps certain cholagogues, exert a favorable 
 action. More importance is attached, however, to a procedure which 
 acts mechanically. We refer to cool enemas. Their action is double. 
 The cold causes the vessels of the large intestine to contract and, by 
 furnishing the liver with a greater amount of blood, stimulates its 
 function. On the other hand, water is absorbed and brought first 
 to the hepatic gland. As the activity of a tissue depends upon its 
 richness in water, when fluid is furnished to an organ, it thus becomes 
 supplied with the element which is indispensable for its activity. 
 
 To sum up, we may increase the protective role of the liver by 
 feeding the patient, by prescribing substances which stimulate the 
 activity of the glandular cells and by administering cold enemas 
 which favor the circulation of the portal vein. 
 
 Protective Role of the Lungs. The lungs also exert considerable 
 influence upon microbes and toxins. The conditions which may 
 disturb their function and diminish or abolish their protective action 
 are not well known. This much is proved, viz., that the lungs act 
 only when oxidations take place in a regular manner. The author 
 demonstrated this by means of artificial circulation, and Cafiero 
 proved the same by causing a mechanical dyspnea in living animals. 
 Inhalation of oxygen should, therefore, be prescribed when the 
 lungs are altered and hematosis is poorly carried on. It is true, as 
 was proved by our experimental researches, that the normal lungs 
 act almost in the same manner, whether ordinary air or pure oxygen 
 circulates in them. When the lungs are altered, however, such can 
 no longer be the case, and the excess of oxygen which is brought to 
 them must compensate for the diminution of the field of hematosis. 
 
 It is likewise possible to stimulate the action of the lungs by favor- 
 ing the circulation. Cold baths are well calculated to accomplish this 
 
THERAPEUTICS OF TNFECTI0U8 DISEASES. 70] 
 
 end, since they diminish passive pulmonary conge tion. Cupping 
 acts in the same way. Certain cardiac medicine may al o be pre- 
 scribed, but most of them stimulate particularly the left ventricle, 
 and consequently exert bul little influence upon the pulmonary 
 circulation. Under these circumstances recourse may be had to 8 
 method which h:is been found efficient by clinical observation in 
 cases <»f pulmonary infections - thai is, blood-letting. 
 
 The Role of the Blood. It, is evidenl thai other parte of the 
 organism must likewise serve for the distribution <>\' microbes and 
 poisons. Our knowledge of this subject, however, U ae yel limited. 
 particularly as regards therapeutic indications of practical use. The 
 organs and (issues as well as (he fluids, and notably the blood, exercise 
 a protective action against- infectious agents. Toxins are destroyed by 
 oxidation in the blood and probably also in the intercellular plasma. 
 If lesions occur in the respiratory apparatus it is necessary, in order to 
 insure the destruction of toxins, to resort to the oxidizing method. 
 Inhalation of oxygen is then indicated. This procedure increases the 
 amount of oxygen in the blood, and its efficiency is further demon- 
 strated by numerous observations and experimental facts. Microbic 
 poisons as well as those of cellular origin are thus annihilated. In 
 this connection it is well to remember what we have repeatedly 
 stated, namely, that oxidations are diminished in the course of infec- 
 tious diseases and typhoid states. There is, therefore, every reason 
 for intervention in all these cases. Dr. A. Robin advised the admin- 
 istration of benzoic acid, which increases oxidation and favors elim- 
 ination of the products of disassimilation by rendering them soluble. 
 This idea seems to us perfectly correct. We, therefore, prescribe 
 from 2 to 4 grams of benzoate of soda daily in grave infectious 
 states, notably when the lesions of the liver, lungs, or kidneys 
 seem to hinder the evolution or elimination of the toxic products 
 originating from disassimilation. If the liver is at the same time 
 disturbed we prescribe in the same potion with 70 grams of julep, 
 4 grams of benzoate of soda and 30 grams of syrup of ether; a table- 
 spoonful is taken every hour. Although oxidation is a general pro- 
 cedure of attenuation of toxins, a by no means less important role 
 is played by the cells which are capable of picking up and digesting 
 microbes and secreting substances which diminish their activity and 
 neutralize their toxins. The therapeutist must, therefore, endeavor 
 to stimulate phagocytosis and favor germicidal and antitoxic secre- 
 tions. Unfortunately, we possess but little information on this sub- 
 
7 1 ! L > INFEi ■ Tl 0U& D TSEASES. 
 
 ject. All we know is that injections of artificial serum give rise 
 to an abundant proliferation of the cells of the bone-marrow. The 
 latter tissue furnishes the economy with the greatest part of the 
 leucocytes charged with the function of defense. Hence it is not 
 difficult to understand the excellent effects of these therapeutics in all 
 cases in which the reactions of the organism seem to be insufficient. 
 Role of the Emunctories. After undergoing in the organism a 
 series of transformations, the toxic substances are eliminated through 
 the various emunctories. Some of them pass into the stomach; 
 others, notably the poisons of the colon bacillus, are thrown into the 
 intestine. Their elimination may, therefore, be hastened by lavage of 
 the alimentary canal. The kidneys, however, are the principal route 
 of elimination. It must be remembered that in the course of infec- 
 tions the urinary secretion is diminished, and in general the toxicity 
 of the urine is also lessened. The physician must endeavor to favor 
 diuresis. For this purpose the patients must be given plenty of 
 water, also enemas which they may retain, at least in part. When 
 necessary, salt-water may also be injected beneath the skin. A 
 second indication is drawn from the state of the blood pressure. 
 With the assistance of Dr. Gamier, the author has found in several 
 cases of scarlatina that when the urinary secretion is very scant, and 
 especially when temporarily suppressed, the blood pressure rises; the 
 heart, by the energy of its contractions, seems to strive to overcome 
 the renal barrier. On the basis of this fact, the physician must 
 endeavor to still raise the blood pressure. Certain medicines may 
 accomplish this end. It is better, however, to resort to cold baths. 
 In patients constantly treated by baths the renal secretion becomes 
 profuse, and, as is demonstrated by the study of urinary toxicity, it 
 carries off noxious substances. The elimination thus being carried 
 on during the entire course of the disease, the mode of its termination 
 is often modified. Such is notably the case in pneumonia in which 
 the urinary crisis, which is no longer any raison d'etre, is not pro- 
 duced. Another cause disturbing diuresis is the fact that the excre- 
 mentitious substances are not sufficiently oxidized. In this connec- 
 tion, cold baths exercise a favorable action which, as already stated, 
 may be completed by the administration of sodium benzoate. This 
 medicine is likewise to be resorted to when lesions of the kidneys 
 hinder the function of these organs. It would then be useless to 
 prescribe diuretics, which would only increase the lesions by stimu- 
 lating the cells which are already diseased. 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 
 
 When infectious nephritis is too intense or exten ive, it. will be 
 necessary to diminish intoxication by stimulating elimination through 
 other channels, notably by the digestive trad and, in gra 
 by blood-letting. The author does not trust much in the vicarious 
 role of sweating. Nevertheless, in certain disea e . thi eems 
 
 to throw out toxic substances. In several cases of diphtheria treated 
 by subcutaneous injections of pilocarpine we noticed, in consequence 
 of sweating, very great amelioration in the general state. It would, 
 therefore, be worth while fco take up this study and to learn whether 
 the old therapeutics, which treated fever patients by giving them 
 hot drinks, diaphoretics, and by covering them heavily, did in cer- 
 tain cases yield good results through the sweating thus produced. 
 
 The secretions of the organism at times eliminate morbid produc- 
 tions resulting from microbic action or a reaction of the economy. 
 Thus, the pseudomembranes of diphtheria localize infection and 
 oppose penetration of the microbe and its toxins into the economy. 
 The organism has done well in producing these pseudomembranes, 
 but it will be equally advantageous for it to eliminate them at a 
 certain period of evolution. Hence, it strives to detach them by 
 means of a secretion of the subjacent glands and by increased activity 
 of the salivary glands. It is easy to stimulate this process by admin- 
 istering sialagogues and notably pilocarpine. The action of this medi- 
 cine upon the heart is much dreaded. It must, therefore, be em- 
 ployed with caution. In adults, however, the author has obtained 
 excellent results from its employment in the treatment of pseudo- 
 membranous anginas and particularly diphtheritic sore throat. He 
 prescribes a subcutaneous injection, morning and evening, of 10 
 drops of a 1 per cent, solution of nitrate of pilocarpine. In twenty- 
 four or forty-eight hours the pseudomembranes are detached and the 
 patient experiences a very notable improvement in his general state. 
 
 Sialagogues may also be employed in all sorts of buccal infections. 
 The one most frequently used is chlorate of potash, which is admin- 
 istered in daily doses of from 2 to 4 grams. The action of this medi- 
 cine is admittedly due to its passage into the saliva. The amount 
 eliminated through this channel, however, is quite small; it amounts 
 to hardly 3 per cent. It is to be recognized, however, that in this 
 case the local treatment has more influence than the salivary exci- 
 tation. 
 
 Medication is also physiological when the elimination undertaken 
 by the organism is stimulated by the employment of the same pro- 
 
764 INFECTIOUS DISEASES. 
 
 cecfures utilized by the economy itself. Bronchial and pulmonary 
 lesions result in expectoration calculated to throw out the exudates, 
 the signification of which is exactly the same as that of pseudomem- 
 branes in diphtheria. Physiological medication consists in prescrib- 
 ing expectorants. These are divided into two groups, according as 
 they act by increasing the force with which the bronchi throw out 
 their contents or by modifying the exudate of the respiratory appa- 
 ratus. Emetics act mechanically. A second group contains expec- 
 torants. The most important expectorants are those which liquefy 
 the exudates. The first among them is chlorohydrate of ammonia, 
 an excellent medicine, which is to be given to children in half-gram 
 doses daily, and from 2 to 4 grams to adults. It may be combined 
 with the salts of antimony. White oxide of antimony seems to the 
 author by far the better preparation, provided it is not employed in 
 too strong doses. The author has obtained excellent results by giving 
 20 eg. to 30 eg. a day. It is an insoluble salt which may be given 
 in water. If emetics are given in small doses so as to avoid vomiting 
 and nausea, they act as expectorants. Ipecacuanha may thus be 
 prescribed in fractional doses : apomorphine, 1 mg. every hour in the 
 form of pills or in a potion. For example, one may prescribe as 
 follows : 
 
 Crystallized hydrochlorate of apomorphine . 0.01 centigram (£ grain). 
 
 Hydrochlorate of morphine 0.03 " (£ grain). 
 
 Hydrochloric acid 3 drops. 
 
 Simple S3Tirp 30 grams (gj). 
 
 Water 90 " (giij). 
 
 Lastly, the syrup of polygala seems to belong to this group, but 
 it should not be employed if there is fever or digestive disorders. 
 
 Physiological medication is applicable to a great number of gastro- 
 intestinal disorders. When the gastric disturbances give rise to 
 nausea, an emetic is called for in order to achieve the work begun 
 by nature by ejecting the substances which encumber and hurt the 
 gastric cavity. Likewise, in patients suffering from diarrhea, which 
 expresses a natural therapeutic tendency, excellent results are often 
 obtained by prescribing a purgative. On the other hand, in certain 
 cases it is advisable to increase constipation; in peritonitis and in 
 intestinal hemorrhage the movements of the bowels may intensify 
 the disorders. It is, therefore, desirable to immobilize the digestive 
 tract. For this purpose opium is mostly prescribed in the form of the 
 extract, 1 eg. every hour. 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 766 
 
 In brief, such are the various medicines which may \»- emplo 
 when we wish to practise physiological medication. All of them 
 increase certain morbid manifei fcation , or, more exactly, they I 
 fche reactions which the organism calls into play in order to combat 
 microbes and I heir toxins. 
 
 Reactions are not always »>f the desirable kind, however. In a 
 great many cases they may give rise to new derangements by their 
 intensity and persistence. They iniisi then be combated. This 
 would be contra-physiological medication, the indication): and pro- 
 cedures of which will be discussed in connection with symptomatic 
 therapeutics. 
 
 Treatment of Inflammatory Manifestations. 
 
 If it were possible in every case to attack the cause of the disturb- 
 ances, the treatment of inflammatory manifestations would always 
 draw its indications from etiology. Antiseptic medication, when 
 applicable, responds to this indication. When the cause cannol be 
 reached, and it is impossible to act upon the mechanism which engen- 
 ders the morbid phenomena, it is necessary to resort to physiological 
 medication. In all cases of inflammation two series of phenomena 
 are to be taken into account: those which occur at the diseased gj ol 
 and require local treatment, and those which result from distui 1 lances 
 engendered by the primary lesion in other parts of the organism and 
 require general treatment. 
 
 Local Treatment. Local treatment may be directed either to 
 moderate or, on the contrary, to stimulate and increase inflammatory 
 manifestations. In the former case the method is called antiphlo- 
 gistic. Now, if we take up the four cardinal phenomena of inflam- 
 mation, we shall see that each of them may quite readily be com- 
 bated or stimulated. 
 
 Hot Applications. Let us first consider heat. Increase in local tem- 
 perature indicates increased activity in nutritive exchanges, which 
 augments the production of heat. At the same time, as may readily 
 be noticed hy applying the hand to the diseased spot, there is in- 
 creased dissipation of heat. Exaggeration of metabolism brings 
 about a more marked vascularization, whence the second phenom- 
 enon, redness. 
 
 In the presence of these two symptoms the therapeutist may think 
 it advisable to stimulate inflammation. He resorts to hot applica- 
 tions. He thus acts upon the production of heat and. it seems, he 
 
766 INFECTIOUS DISEASES. 
 
 practises naturalistic therapeutics. It is to be noted, however, that 
 by this local treatment he imperfectly imitates nature, for it hinders 
 the second phenomenon — i. c, increased radiation. If, for example, 
 the diseased part be immersed in very hot water, or if hot compresses 
 be applied, the temperature is evidently increased, but radiation 
 diminishes. - Nevertheless, this method yields good results. It is 
 utilized especially in cutaneous inflammations. In the treatment of 
 erysipelas the author applies upon the affected parts compresses of 
 gauze clipped either in hot water or some weak infusion. Such com- 
 presses should not be allowed to become cold, for the evaporation of 
 the water dissipates the heat and produces a contrary result. Hot 
 poultices have the advantage of better preserving heat, and may be 
 prescribed under the same circumstances. In order to avoid the 
 inconvenience resulting from evaporation or moisture, the diseased 
 part may be surrounded with rubber tubes in which hot water is 
 circulated. It is likewise possible, in the case of the abdomen, to place 
 upon the part rubber bags filled with hot water. When treating the 
 extremities one may employ for the same purpose small bags filled 
 with sand, which may be placed under and around the limbs, while 
 the upper surface may be covered with a bag of hot oatmeal in order 
 to avoid too much weight. Lastly, when the lesion is well circum- 
 scribed, hot air may be employed, as, for example, in the case of soft 
 chancre. 
 
 Refrigeration. Refrigeration may be accomplished by application 
 of cold compresses or poultices, by circulation of cold water in tubes, 
 by cold air and application of bags filled with water or ice. When 
 an ice-bag is employed a flannel should be interposed between the 
 bag and the skin in order not to hurt the skin. This method evidently 
 increases radiation and diminishes heat ; on the other hand, it gives 
 rise to vasoconstriction, which causes the second cardinal phenome- 
 non — i. e., heat — to disappear. This method is hardly ever applicable 
 to superficial lesions. Inflammations of the skin, of subcutaneous 
 tissue, and of lymphatic glands should not, as a rule, be treated by 
 means of refrigeration. These inflammations already have a certain 
 tendency to sphacelation, which would be increased by cold. Brown- 
 Sequard believed that cold and hot applications should be used 
 alternately; the reverse modifications which are thus produced in the 
 vessels hinder the production of gangrene. The author believes that 
 heat is sufficient for this purpose. 
 
 The refrigerating method, on the contrary, renders immense service 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 767 
 
 in the treatment of deep inflammations. In acute inflammatioi 
 the abdominal organs, in appendicitis, peritonitis, and periuterine 
 lesions remarkable results are obtained. Likewi e, the application 
 of an ice-bap; upon the precordial region or upon the cranium is 
 classical in cases of inflammation of the pericardium or menii 
 respectively. The author employs the same method when, in the 
 course of otitis, he finds Bymptoms of mastoiditis. The appli- 
 cation of the ice-bag upon the mastoid region succeeded, in several 
 
 cases, in arresting the accidents. It must be home in mind, how 
 that care should be taken not to allow the bag to grow warm. When 
 the ice-bag is used it must be renewed from time to time. 
 
 Cold may likewise he employed to assuage the third cardinal 
 phenomenon — pain. It produces very marked sedation and acts 
 upon the pain of mastoiditis or osteomyelitis as well as upon that of 
 orchitis. The action of cold is complex. Besides the waste of heat, 
 cold causes constriction of the bloodvessels. Not only the small 
 arteries of the skin but also those of the deeper parts become con- 
 stricted. The experiments of F m lericq leave no doubt in i hi- regard. 
 The application of the ice-bag upon the cranium produces constric- 
 tion in the cutaneous and meningeal arteries. The latter are too 
 rapidly reached to permit the supposition that the phenomenon is 
 due to the propagation of cold; it is probably a process of reflex vaso- 
 constriction. 
 
 Moreover, cold increases the tonicity of the vascular muscles as 
 well as those of the myocardium. The latter result has considerable 
 importance. Application of the ice-bag over the region of the heart 
 may be prescribed in all cases of myocarditis whenever it is necessary 
 to render the function of the organ more regular and energetic. 
 
 Immobilization. Every inflammatory lesion causes pain and swell- 
 ing which disturb considerably the function of the affected parts. 
 The patient instinctively immobilizes himself as much as possible. 
 Rest of the inflamed parts is one of the best therapeutic measures. 
 It is constantly resorted to in surgery. The application of splints 
 and apparatus is designed to prevent every movement of the inflamed 
 parts, and thus complete the natural work. In certain cases it is 
 possible to arrest the inflammatory swelling by means of a methodic 
 compression; but this latter method is hardly ever indicated in c - - 
 of acute inflammation. The results obtained by submitting inflamed 
 parts, and notably the skin affected by erysipelas, to the elastic 
 compression of a layer of collodion have not been encouraging. 
 
INFECTIOUS DISEASES. 
 
 Compression may be useful by hastening the absorption of exudates 
 only after the acute phenomena have passed away. 
 
 Depletion. Inflammatory congestions and exudations are often 
 combated by depletion. Scarifications upon the diseased parts are 
 useful, as they permit the discharge of a small amount of blood or 
 serosity. thus relieving considerably the painful tension of which the 
 patient complains. Some have even attempted to arrest the progress 
 of certain inflammations in this manner. Thus, scarifications have 
 sometimes been practised upon an erysipelatous patch. The pro- 
 cedure does not seem, however, to have given satisfactory results. 
 
 Revulsion. Revulsion is often practised upon the region of the skin 
 corresponding to the diseased organ as well as in distant parts. Dry 
 or scarified cupping of the precordial region and sometimes applica- 
 tion of leeches are often prescribed in cases of acute inflammation of 
 the cardiac muscle and especially of the serous membranes. The 
 same means are applied in the treatment of pleuropulmonary and 
 abdominal inflammations ; or, instead of these mechanical procedures 
 irritating substances, such as mustard poultices, friction with croton 
 oil, and application of certain plasters may be prescribed. In other 
 cases applications are made to distant parts. In cases of thoracic 
 or cerebral inflammation revulsion is effected by cupping the extremi- 
 ties, applying leeches to the anus or mustard plasters upon the legs. 
 In the conception of the ancient practitioners, all these medications 
 had the same object. They were intended to draw the inflammation 
 of the diseased organ toward those parts of the organism where it 
 would cause no harm. Such was the idea of Hippocrates, who prac- 
 tised revulsion, and in this manner proposed to draw away the 
 humors which threatened to attack an important organ. Most 
 modern therapeutists, instead of the humoral hypothesis of revulsion, 
 hold the nervous theory to be true. They admit that excitation at 
 one point causes, by means of inhibitory acts, palliation of congestive 
 and inflammatory phenomena occurring in another part of the econ- 
 omy. The revulsive application calls into play the sensory system, 
 and coincidently it produces a series of circulatory modifications. 
 
 Among the revulsives, some, like sinapisms, cause congestion in 
 the skin, and thus modify the water content of the blood. Others 
 produce extravasation of a quantity of blood ; such is the case in dry 
 cupping. Still others produce local blood-letting. In the last-named 
 case, between the superficial and the profound circulation a balancing 
 is admitted. The effect is deeper, however, and the flow of blood 
 
THEEAPEUTI08 OF INFECTIOUS DI8EA8E8. 769 
 
 may relieve the venous system. To this end blood letting should be 
 
 practised at a, determined point. Thus, in order to 'liinini h pa 
 
 congestion of the brain, leeches must be applied upon Hi'' ma 
 processes. When action upon the liver is desired, they are placed 
 about the anus or even upon the anal mucous membrane. Hepatic 
 depletion is explained by the vascular connections which unite- t|,i- 
 region to the portal system. 
 
 In brief, revulsion seems to acl in two ways: by producing deple- 
 tion of blood and a reflex excitation, expressed by an inhibitory 
 action upon the inflamed part. Ii is probably owing to nervous con- 
 nections between the superficial and deeper parts of a region thai 
 revulsion is effected, preferablyin the pari corresponding to the dis- 
 eased organ. This mode of excitation belongs to all revulsives, 
 because all produce excitation of the nerve terminations. Some < i 
 them also give rise to circulatory modifications by inducing conges- 
 tion, ecchymoses, or depletion. In the latter case ;i general modifi- 
 cation in the blood is produced in addition to the local change. The 
 remarkable effects of local depletion are not, however, to be attrib- 
 uted to the latter result. All scarified cuppings applied to the pre- 
 cordial region do not act like general blood-letting. It is, therefore, 
 probable that there is a harmony in the vascular or vasomotor system 
 of the same segments of the body. A modification produced in the 
 local circulation of one part of the segment must affect preferably 
 and in a special manner the subjacent parts. Whatever be the 
 theoiy, the practical importance of revulsion is undeniable. It is 
 resorted to in two cases, namely, at the beginning of inflammation 
 and at its terminal period. 
 
 At the beginning the immediate result of revulsion is frequently 
 to assuage one of the elements of inflammation to which we have thus 
 far hardly referred, viz., pain. The pain in the side felt in pneu- 
 monia rapidly yields to a few dry cuppings and still more readily to 
 scarified cuppings. The same is true of the painful distress of patients 
 suffering from acute pericarditis. At the same time the congestive 
 phenomena are rapidly palliated and, consequently, the inflamma- 
 tion is relieved. It may be objected that inflammatory reaction is 
 of secondary importance and that there is no advantage in combating 
 it. This remark would be perfectly exact if the organism always pro- 
 portioned its efforts to its needs. As we have time and time again 
 remarked, however, slight causes often produce extremely violent 
 reactions. We may recall, for example, a benign cutaneous lesion. 
 
 49 
 
770 IXFECTIO US DISEASES. 
 
 such as furuncle. Around the small lesion, which must arrest and 
 destroy the staphylococcus, an edema develops which sometimes 
 assumes enormous proportions. When the seat of the phenomenon 
 is the skin no great harm results; but if the process occurs in a vital 
 organ. like the heart, the diffusion of the lesion may have fearful 
 consequences. Hence, revulsion is necessary, and it is the more useful 
 as the affected part occupies a higher rank in the organic hierarchy. 
 
 Revulsion is likewise employed at the end of the morbid evolution 
 when recovery is tedious. In this case depletive measures are not 
 resorted to ; but excitants, such as sinapisms, vesicatories, and ther- 
 mal cauterizations are applied. By excitation of the nerve ends we 
 bring about increased nutritive activity of the parts which are oper- 
 ated upon and those which are subjacent. 
 
 We thus arrive at the conclusion that revulsion is not compre- 
 hensible unless we admit a nervovascular synergy establishing a 
 morbid sympathy in the various segments of the body. According 
 to this view, it is intelligible why revulsion practised upon the spinal 
 column influences the viscera. While certain parts possess a relative 
 autonomy, all are united by numerous synergies. Hence, it is con- 
 ceivable that a local modification may produce extensive effects. 
 It is for this reason that we may act upon a thoracic organ by apply- 
 ing revulsives to the lower extremities. 
 
 In the beginning of all local inflammations local revulsion must 
 be practised. The choice of the revulsive varies with the age and 
 state of the individual. In young children we have often to treat 
 pleuropulmonary inflammations. We must resort to mustard poul- 
 tices and baths, and envelop the patient with moist sheets. It is 
 to be borne in mind that blood-letting, even of a local character, is 
 not, as a rule, well borne by children. In the case of vigorous adults, 
 scarified cupping represents the best method of taking blood. In 
 debilitated subjects and delicate women milder revulsives, such as 
 dry cupping, sinapisms, must generally be resorted to and, in graver 
 cases, thermocauterization. Intervention must be more energetic 
 the more important or delicate the affected part. Cardiac and cere- 
 bromeningeal manifestations thus require the promptest intervention . 
 
 When chronic lesions are to be dealt with, thermocauterization, 
 vesicatories, and at times simply application of tincture of iodine, are 
 employed. An abscess (Vabc&s par fixation) produced by means of 
 a subcutaneous injection of turpentine is a method related to the 
 group of revulsive procedures. Its mode of action has been discussed. 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 77] 
 
 Some authorities contend thai the circulating bacteria are attracted 
 to the abscess, others admit a modification produced in the phago- 
 cytes and hematopoietic organs. This method, firsl employed in 
 puerperal U'.vcv, then in various septicemias, ha been utilized with 
 
 success in the treatment of grave pneumonias. 
 
 Vasomotor and Depletive Medications. 
 
 We have thus far reviewed the methods which acl locally upon 
 inflamed parts. There are, however, other modes of treatment which 
 modify the general state. The therapeutisl may have two object* 
 
 in view: to stimulate or attenuate inflammatory manifestations. In 
 the former instance he employs vasodilators, and administers, for 
 example, trinitrin, or causes the patienl to inhale nitrite of amyl. 
 
 We often resort to the first of these medicines in the Ireatmcnl of 
 erysipelas. In certain cases characterized by a tedious course and 
 lingering resolution, truly interesting results are obtained. Inhala- 
 tion of amyl nitrite has been employed by Dr. Hayem in the treat- 
 ment of pneumonia. 
 
 On the other hand, when it is desired to check the inflammatory 
 phenomena, ergotin or tartar emetic is sometimes prescribed accord- 
 ing to the method of Rasori. The latter medicine is employed espe- 
 cially in pneumonia. When the individual is vigorous and the con- 
 gestion is extreme, from 10 eg. to 20 eg. of it is prescribed in a potion 
 of 120 grams (lj- grains to 3 grains in 4 ounces); a tablespoonful is 
 given every two hours. 
 
 Another method consists in combating inflammation by means of 
 general depletion. Two procedures are at our disposal : we may give 
 rise to a serous exudation, and for this purpose, purgatives and dras- 
 tics are prescribed. This medication is alike evacuative and revul- 
 sive, as it not only causes depletion but intestinal irritation as well. 
 All inflammations do not require this method. It is indicated par- 
 ticularly in meningeal and cerebral inflammations. Calomel is pref- 
 erably employed. In adults this substance is administered in doses 
 of from |- gram to 1 gram (8 to 15 grains) divided into three powders 
 and given at intervals of fifteen minutes. In children from 10 eg. to 
 30 eg. (1^ to 5 grains) are prescribed; 15 or 20 grams (half an ounce | 
 of castor oil is given the following day. This is the classical practice 
 in England, and is to be recommended. A last therapeutic means 
 consists in producing depletion by blood-letting. In view oi the im- 
 portance of this method, we shall devote to it a special chapter. 
 
772 INFECTIOUS DISEASES. 
 
 Having studied inflammation and its treatment in a general man- 
 ner, it now remains to consider the therapeutics of its various con- 
 sequences. We shall begin with the study of exudates. 
 
 Treatment of Inflammatory Exudates. 
 
 Treatment of Serous Exudates. When inflammatory exudates 
 acquire a certain volume or occupy an important organ or tissue, 
 they require treatment varying according to their seat and nature. 
 Then nature may be serous, pseudomembranous, purulent, or putrid. 
 
 The serous exudates exert upon the pathogenic microbes a germi- 
 cidal influence and, consequently, represent a salutary reaction. It 
 wall suffice, for example, to recall variola. In its confluent forms 
 the edematous swelling of the face and hands constitutes an excellent 
 sign of prognosis. In certain cases, however, the effusion takes place 
 in an important organ or a delicate tissue. It may then have two 
 inconveniences : at times, owing to its large volume, it acts mechani- 
 cally and hinders the regular function of the organ. At other times 
 it separates superficial parts from deeper layers, and thus embarrasses 
 their circulation and nutrition, and may even cause their mortifica- 
 tion. In a more advanced degree the exudate, instead of being simply 
 diffuse, predominates at one point. It may then raise the skin or 
 the mucous membrane, producing bullae or phlyctenular. This is 
 what occurs in the most varied affections, such as herpes, varicella, 
 erysipelas, pemphigus, etc. When a serous cavity is adjacent to the 
 inflamed part the fluid naturally flows into it. Pleurisies, peritonites, 
 pericardites, meningites, vaginites, and arthrites which are the equiv- 
 alents of edemas and bulla;, are thus produced. The disposition of 
 the tissues being more favorable for the free flow of the fluids, the 
 latter exude in greater profusion. 
 
 The effusion taking place in a serous membrane likewise represents 
 a germicidal exudate. Its relations to the subjacent organs, how- 
 ever, produce a certain number of functional disturbances and sug- 
 gest some interesting therapeutic indications. Thus a pleurisy, on 
 account of its abundance, may embarrass pulmonary hematosis and 
 give rise to progressive asphyxia, and even cause sudden death. In 
 face of these dangers the question is whether the exudate is to be 
 respected on account of its advantages. By compressing the lungs 
 and restricting their expansion, by hindering their function, the effu- 
 sion checks their activity and condemns these organs to a state of 
 relative rest, or it brings about immobilization recalling that which 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 11?, 
 
 the physician practises upon a diseased joint. The problem Hum 
 becomes highly complex. If would be equally rational to argue thai 
 the off union, l>y restricting pulmonary activity, hinder) hemato i . 
 and consequently disturbs the entire organism. On the other hand, 
 it may l>e contended thai the effusion aecea itatei a relative re I on 
 the part of the diseased lung, and thus favors cicatrization of the 
 lesion. The interest of this discussion is do1 merely one of pecula- 
 tion; on the contrary, it guides therapeutics, [f the bad effed 
 thought to overbalance the advantages, early iuifrvniion i- n<-<-<:— 
 sary to evacuate the fluid by thoracentesis. On (he other hand, the 
 physician should tiol intervene unless the effusion, owing to it- greal 
 abundance, threatens to produce grave disorders. Even then, how- 
 ever, evacuation of only a small amount of the exudate will suffice, 
 because complete evacuation is often followed by a too energetic flux 
 of the blood into the previously compressed vessels, am I a consequent 
 intense congestion. It is, therefore, almost universally agreed thai 
 the operation should not be performed during the acute stage. The 
 intervention is to take place after the effusion has become stationary. 
 If the fluid tends to be absorbed then nothing is to be done. On 
 the contrary, if it persists without any notable modification, inter- 
 vention is indicated. If the fluid is allowed to remain too long, 
 atrophy of the lungs, thickenings, and adhesions may occur, which 
 embarrass the function of the organs and bring about deformity of 
 the thorax. Thoracentesis is practised generally toward the fifteenth 
 day in children and the twentieth day in adults. All the fluid is not 
 drawn, however; at most one quart (one litre) should be evacuated. 
 If the fluid is reproduced a new puncture may be made. In most 
 cases, however, after the first evacuation absorption is completed of 
 itself. This fact is not to be wondered at. It is the application 
 to serous membranes of the general law of pathology. Every mi- 
 crobic lesion at the end of a certain time no longer tends to arouse 
 organic reactions. The economy becomes accustomed to the presence 
 of an infectious focus which at first arouses its susceptibility. A 
 modus vivendi which may be prolonged almost indefinitely is thus 
 established. Intervention is then indicated. The organism being 
 sluggish, the operation renews the inflammatory process and pro- 
 duces an increased circulatory activity in the lungs, and the change 
 thus caused is eminently favorable to the absorption of the exudate. 
 There is another question to which hardly an allusion has thus far 
 been made. Do exudates in general or, what is easier to study, 
 
774 INFECTIOUS DISEASES. 
 
 pleural effusions contain figurate elements or soluble substances 
 exerting any action whatever upon the organism, either favorable 
 or otherwise? At present it is well known that even serous and 
 transparent effusions alwa) r s contain leucocytes. What is the sig- 
 mficance of then presence from the standpoint of the protection of 
 the organism? Of this we know nothing, and we do not comprehend 
 their role in those cases in which the exudate is germless. On the 
 other hand, as has already been stated, even a serous effusion may 
 contain bacteria, notably streptococci. In the case of tuberculosis, 
 it often contains the specific bacillus, as has been demonstrated by 
 inoculations into animals. This presence of microbes in certain 
 exudates might, perhaps, justify and command earlier intervention. 
 The author says "perhaps," because, besides the difficulty encoun- 
 tered in determining whether living bacteria are present in an exudate 
 or not, it may furthermore be questioned whether these bacteria are 
 really noxious. Immersed as they are in a great amount of germi- 
 cidal fluid, they seem to have lost all pathogenic action, since they 
 are incapable of inducing even a purulent transformation of the 
 exudate. Investigations should be pursued on this subject. It would 
 also be interesting to take up the study of soluble toxic or antitoxic 
 substances which may be present in an exudate. Dr. Gilbert (of 
 Geneva) laid down the problem by showing that the fluid of tuber- 
 cular pleurisies, when injected beneath the skin, exerts a curative 
 action. It is true that the fact has been doubted. The author has 
 therefore, with Dr. Josue, pursued some researches with the fluid of 
 experimental diphtheritic pleurisies. The results were negative, inas- 
 much as the fluid experimentally produced in guinea-pigs contained 
 neither toxin nor antitoxin. 
 
 We have expanded upon pleural effusions, for they are the most 
 frequent, while exudates in other serous membranes are of quite 
 uncommon occurrence. While, in the case of pleurisies the physician 
 must be guided in his intervention by the physical signs and the 
 course of evolution, and not by the functional disturbances which are 
 extremely deceiving, in the case of pericardial or meningeal effu- 
 sions he must act altogether differently. In the case of the peri- 
 cardium the physician must intervene when the effusion endangers 
 the function of the heart, and in the case of the meninges, when 
 the exudate produces compression and intense headache. Lumbar 
 puncture relieves the pain and temporarily reduces the increased 
 intrameningeal tension as well as certain alarming phenomena, 
 
THERAPEUTICS OF INFECTIOUS DISEASE8. 775 
 
 notably coma. In most cases amelioration i tran itorj and only 
 delays the fatal termination. Neverthele , there are certain < 
 on record in which repeated punctures seem to haVe contributed to 
 recovery. M any rate, this inoffem ive operation eem dei tined to 
 be retained in medical practice as a palliative. 
 
 Acute inflammations of the peritoneum, unlike those of the pleura, 
 seldom result iii aserous effusion which, in case if should be produced, 
 is too small in amounl to necessitate operal ive intervention. In fact, 
 there is a production of pseudomembranous exudates which embar- 
 rass intestinal movements. 'This is a fortunate event, since the 
 extension of the peritoneal inflammation is nothing else than a series 
 of inoculations which lake place from point to point ac a resull of 
 contractions of the intestine. It is well, therefore, to complete the 
 work of nature by further immobilizing the intestinal coils, a resull 
 that may be obtained by the administration of opium or morphine. 
 Operative intervention is at times indicated only in subacute or 
 chronic infections, and notably in tuberculosis. Two kinds of opera- 
 tions may be performed: one simply palliative, the other curative. 
 In the so-called ascitic form of tubercular peritonitis paracentesis is 
 practised because the effusion, owing to its abundance, produces 
 functional disorders. The liquid, however, is seldom sufficiently pro- 
 fuse to render this operation necessary, and, on the other hand, it is 
 generally contained between adhesive bands of pseudomembranes 
 which prevent its free flow. It is true that the operation may be 
 completed by irrigating the serous membrane by means of boiled 
 borated water at 102.2° or 104° F. (39° or 40° C). Irrigation is 
 continued until the returning fluid becomes perfectly clear. This 
 method, for which we arc indebted to Dr. Debove. has been employed 
 with success in a number of cases. The irrigations are followed by 
 a sufficiently strong inflammatory reaction. The lesions subse- 
 quently undergo resolution. Another procedure, the efficacy of 
 which was demonstrated by the experiments of Dr. Teissier, col 
 in injecting into the peritoneum sterilized gases — oxygen or nitrogen. 
 
 Lastly, one of the most extraordinary therapeutic methods applied 
 to tubercular peritonitis is laparotomy. The peritoneal cavity is 
 opened, and then, after irrigation by means of boiled water, it is 
 dressed. As a result the lesions subside. In this manner recovery 
 has been obtained in 7.5 per cent, of the cases in adults and 87 per 
 cent, in children. This is what takes place, at least in the ascitic 
 form. In the ulcerative variety, out of twenty-two laparotomies nine 
 
776 1SFECTI0US DISEASES. 
 
 were followed by death. Out of thirteen other patients, only three 
 remained in a satisfactory slate. Finally, in the fibrous variety, 
 recovery reaches 65 per cent. The mechanism of recovery following 
 operative intervention has been a subject of extensive discussion. 
 Numerous experiments have been undertaken bearing upon this 
 subject. All clinical as well as experimental documents show that 
 laparotomy succeeds particularly in those cases which tend toward 
 recovery or at least toward a chronic state compatible with life. The 
 slightest cause is then sufficient to arouse the sluggish reactions of 
 the organism. Laparotomy, still better than aseptic irrigations or 
 injections of gas, produces a slight inflammation and, necessitating 
 an effort of reparation on the part of the organism, brings about 
 cicatrization of both the operative wound and the pre-existing 
 lesions. The organism, being forced to supply cells and to secrete 
 exudates for the reparation of the surgical incision, resumes coinci- 
 dent ly the work which it had once begun for the destruction of the 
 tubercle and of the infectious agents living therein. In brief, all 
 these therapeutic procedures act simply by awakening a curative 
 inflammation which had too soon fallen into slumber. 
 
 Serous effusions of the tunica vaginalis or of the articular synovials 
 seldom invite operative intervention. In cases in which the pain 
 caused by inflammation of the tunica vaginalis is very intense, a 
 puncture is practised which, diminishing the tension, causes the 
 painful phenomena to disappear. Finally, as in the case of the pleura, 
 when the effusions pass into a chronic state and present no tendency 
 to absorption, the fluid must be evacuated. As in the case of the 
 pleura, however, it seems that effusions of the serous membranes are 
 always produced consecutively to a lesion of the neighboring parts, 
 and especially of subjacent organs. Hydrocele is a true chronic 
 inflammation of the tunica vaginalis. It is to be noted that, unlike 
 what occurs in other serous membranes, evacuation of the fluid does 
 not suffice to bring about recovery. It is necessary, in addition, to 
 inject an irritant and give rise to a curative inflammation. 
 
 In those cases in which the serous exudates raise the epidermis or 
 the epithelial lining of a mucous membrane which is readily accessible 
 immediate intervention is evidently indicated. The bulla should be 
 punctured by means of a sterilized needle, and the fluid evacuated 
 by gentle pressure with the finger. The operation is done precisely 
 as in the dressing after the application of a vesicatory. By this 
 small operation the painful tension is diminished and the liquid 
 
THERAPEUTICS OF INFECTIOUS DISEA8ES. Ill 
 
 containing microbes and toxins is thrown out. Finally, repair us 
 favored because, wiilioul this precaution, suppuration or ulceration 
 might take place. 
 
 When serous exudates are produced in visceral cavitie and oot- 
 ably in the digestive bract, an easy issue is assured. The organism 
 daily employs this means of defense. Vomiting and diarrhea repre- 
 sent the production of serous secretions designed to combat infec- 
 tion, viz., to eliminate microbes and their toxins. Therapeutii 
 guided by the same principles in prescribing emetict and purgati 
 These medicines produce secretions which wash the affected parts. 
 An emetic may likewise serve to eject exudates produced in the 
 respiratory apparatus. The movements of the diaphragm :md the 
 thoracic muscles compress the lungs and expel the pathological fluids 
 encumbering (hem. 
 
 Treatment of Purulent Exudates. While serous exudate- are dan- 
 gerous only by their quantity and the disturbances which they 
 mechanically cause in the neighboring organs, purulent exudates are 
 of greater importance and require more prompt intervention. 
 
 Purulent transformation is indicative of great activity on the pah 
 of the pathogenic agents. Their toxins give rise to profuse diape- 
 desis. While the leucocytes are not killed in the yellow serous exu- 
 date, in pus they undergo a special transformation — a fermentation 
 — which causes their death and changes them into useless foreign 
 bodies. As has already been stated, a serous effusion produces noth- 
 ing more than mechanical disturbances. A purulent effusion, on the 
 other hand, modifies the organism more profoundly. The general 
 state is affected, fever sets in, and grave phenomena may appear. 
 This different mode of action of the two kinds of effusions results in 
 profound difference in the reactions of the organism. When effusion 
 is of a serous character, the organism makes no effort to throw it 
 out; when effusion is purulent, modifications which terminate in the 
 evacuation of the morbid focus occur. This is the tendency of every 
 purulent focus, viz., to open outward or into a cavity. These spon- 
 taneous openings, however, have three inconveniences: they may 
 occur in an organ of great physiological importance or enter a cavity 
 which may serve as an excellent medium for the multiplication of 
 the microbe. The result is often the occurrence of serious accidents 
 rapidly ending in death. A visceral abscess, until then well borne. 
 when it discharges into the peritoneal cavity, produces inflammation 
 in the serous membrane which ends fatally. In this case the organ- 
 
778 1XFECTI0 US DISEASES. 
 
 ism follows its tendency to throw out the harmful element, but its 
 intervention is blind and gives rise to graver disorders than the 
 primary lesion. 
 
 The second inconvenience of spontaneous openings, even of those 
 which occur under favorable conditions, is that they are effected too 
 tardily. The consequence is that the organism is subjected too long 
 to the action of toxins and that the adjoining parts of the purulent 
 focus are too profoundly altered to recover. Finally, the spontaneous 
 openings are generally too small, the discharge is not well effected, 
 and the pus stagnates and may undergo putrid decomposition. Or 
 else fistulous tracts are produced, ending in the formation of per- 
 manent fistulae. If suppuration is finally arrested, deformed cica- 
 trices persist which often cause functional difficulties. These con- 
 siderations explain why timely intervention is necessary. Incision 
 permits the flow of the pus under the most favorable conditions at 
 the most favorable point, through a sufficiently large opening and 
 at a period when the economy is not too profoundly intoxicated and 
 when the neighboring parts of the focus are not yet deeply affected. 
 Incision must be practised as soon as the pus is collected, and it 
 must be made at a low point. If the focus is large and presents 
 ventricles, it is often necessary to make count eropenings. In order 
 to assure the flow of the fluid and prevent the incision from closing 
 prematurely, the lips of the wound should be kept open by means 
 of gauze or drainage-tubes. When dealing with a voluminous but 
 well-circumscribed abscess, situated in the face or neck, the author 
 has been in the habit of making a small puncture and introducing 
 into the focus Florence horsehair curved in arch-shape in order to 
 avoid a cicatrix. In this way a very easy discharge is assured, and 
 the incision is so small as, in most cases, to leave no visible mark. 
 
 In all cases the discharge should continue for a few days following 
 the incision. The exudate then represents a sort of washing per- 
 formed by the organism for eliminating the microbes and toxins. 
 Guided by this fact, lavage with aseptic or slightly antiseptic fluids 
 may be employed, and the work of nature thus be completed. These 
 lavages also have the advantage of detaching and washing out dead 
 cells, small foreign bodies, and at times sequestrse. Spontaneous 
 rejection of these harmful elements is long and difficult. Even lavage 
 may be insufficient to carry them away. Then curettage and, in 
 certain cases, more important operations are resorted to for the 
 purpose of exposing necrosed parts and extracting them. An osseous 
 
THERAPEUTICS OF INFECTIOUS DISEASES. ~",'.i 
 
 sequestrum, for example, may keep up 8 discharge for years, but 
 when it is extirpated, recovery follow in a i<-v. d&] 
 
 Medical advance, by enabling the practitioner to detect visceral 
 suppurations and establish their localization by the study of symp- 
 toms, have led him to intervene in ca e of deep eated lesions, 
 visceral abscesses, such as those of the liver, kidneys, and lung . or 
 of the nervous centres, and t<> open serou cavities, and to trepan ;i 
 bone. Surgical intervention is not, however, always indi pensable. 
 Purulent foci are sometimes suppressed spontaneously, and the 
 microbes perish. The pus is then absorbed or undergoes fatty meta- 
 morphoses, or else it is transformed into a semisolid mass which may 
 later become iu(illr;ited with calcareous salts, and thus be rendered 
 entirely inoffensive. In order to formulate the rules of intervention, 
 we must take into aceounl ;i good many factors, such as the seat of 
 the lesion, the nature of the causative microbe, the course of the local 
 symptoms, and the concomitant general phenomena. As regards 
 localization, it will suffice to recall what occurs in the serous cavities. 
 Intervention must be immediate in the case; of the peritoneum, in 
 order to prevent an early fatal termination, and it must be prompt 
 in the case of articulations, in order to prevent consecutive ankyl< «is. 
 On the other hand, purulent pleurisy is far better borne, and at 
 times, when it is encysted, it may heal spontaneously by vomica. 
 Early intervention is, however, preferable, since it prevents second- 
 ary alterations of the lungs and pleura. The nature of the causative 
 agent is also to be considered. .As a rule, suppurations with strep- 
 tococci require rapid intervention and radical operation. A large 
 incision, assuring an easy flow, is indispensable. Suppurations due 
 to pneumococci are less liable to be reproduced and often recover in 
 consequence of simple evacuative puncture. Finally, non-microbic 
 suppurations are commonly well borne and may be absorbed with- 
 out operative intervention. 
 
 Besides bacteriological examination, which alone can conclusively 
 demonstrate the nature of the causative agent, therapeutic indica- 
 tions may be drawn from the local and general phenomena. Thus 
 the author lias seen the development of a pleuritic effusion during 
 convalescence from typhoid fever. This effusion, occurring without 
 any functional disturbance and giving rise to no fever, seemed to be 
 of a serous nature. In order to assure the diagnosis, however, a few 
 days later the author made an exploratory puncture, which brought 
 out a seropurulent liquid. The latter, however, contained no microbe. 
 
780 INFECTIOUS DISEASES. 
 
 but agglutinated energetically the typhoid bacillus. As the general 
 state seemed to be very satisfactory, he did no more than apply a 
 few cutaneous revulsives, and the fluid was gradually absorbed and 
 disappeared. Here is a case in which the study of the morbid symp- 
 toms did not justify intervention; but in the case of an erroneous 
 interpretation of the nature of the effusion, exploratory puncture, 
 by giving exact information, might have modified our first conclu- 
 sion. Bacteriological examination, however, brought us back to the 
 idea of abstention, and the evolution demonstrated that hi fact it 
 was useless to intervene. 
 
 We cannot review all the indications and contraindications that 
 are to be taken into account when the rules of intervention are to 
 be settled. While in certain cases these rules are relatively simple, 
 in others discussion is not yet at an end. It will suffice to recall what 
 occurs as regards appendicitis. The lesion is not treated by incision 
 of the focus, but by extirpation of the diseased organ. While certain 
 surgeons operate as soon as the diagnosis is made, others prefer to 
 wait and not intervene until after the disappearance of the acute 
 symptoms. In view of the discussions that have taken place and of 
 the contradictory facts that have been reported, it may be stated 
 that at the present time no problem is more troublesome, no question 
 engages more responsibility or produces more anxiety than the advice 
 to be given in cases of appendicitis. 
 
 Although surgical intervention is possible when suppuration is 
 localized at a point, it cannot evidently be resorted to against small 
 disseminated lesions. We may open a pulmonary abscess, but we 
 are unable to intervene against a purulent bronchitis or a broncho- 
 pneumonia which has terminated in multiple lobular suppurations. 
 In this case the organism endeavors to eject the purulent exudates 
 by coughing and at times by vomiting. The physician must act in 
 the same manner. He must prescribe substances which favor lique- 
 faction of the exudate and, consecutively, its ejection through 
 expectoration. The sulphur and antimony preparations are indi- 
 cated here. If this medication proves insufficient, an emetic may 
 accomplish more thorough cleansing of the respiratory apparatus. 
 While, however, an emetic yields good results in young children, the 
 older the patient the less easily he can bear it. It should never be 
 employed in the aged, since it may, by the efforts which it produces, 
 cause vascular ruptures or, at least, give rise to considerable depres- 
 sion and collapse. 
 
THEBAPEUTI08 OF INFECTIOUS DISEASES. 781 
 
 Treatment of Pseudomembranous Exudates. The third vai 
 of inflammatory exudates is represented by pi eudomembrai 
 dates. The therapeutic rule i: p here very simple. The fal e mem- 
 brane is a barrier opposed to the infection, l»ui il i- bill of microb< ■ 
 and toxins. The organism should, therefore, be freed from it. Tib- 
 may be accomplished by irrigations, scrapings, forcible removal of 
 the membrane, and cleansing by means of forcep 01 cotton. The 
 only precaution to be I a ken is to avoid as much a po rible hurting 
 the subjaeenl niucous nienibrane. Ii is precisely for this reason thai 
 many advocate abstention, al least in cases of angina, since too 
 energetic intervention might harm the mucous membrane. They 
 endeavor to detach (he pseudomembranous exudates by means of 
 irrigations. Al any rale, intervention is far leSfi Ulgenl than in cases 
 
 of suppuration, for tlie pseudomembrane represents a barrier oppos- 
 ing the progress of the infection. As we have several times remarked, 
 
 while warding off certain dangers the pseudomembrane may create 
 others. By reason of its localization it may bring about serious 
 functional disturbances and necessitate surgical intervention, such 
 as tracheotomy, which is rather a palliative. 
 
 Treatment of Gangrenous Lesions. The more noxious the inflam- 
 matory exudates the more prompt and energetic intervention must 
 be. In the case of a gangrenous or putrid lesion, operation must be 
 performed as soon as possible, for the reason that the toxins produced 
 by the microbes are so strong that the cells in contact with them 
 cannot react, but die and undergo putrefaction, which adds new 
 harmful substances to the medium. These putrid poisons being 
 absorbed, impregnate the entire economy and rapidly produce a very 
 grave general condition. 
 
 As soon as the existence of a putrid or gangrenous focus is deter- 
 mined, it must be freely incised and, if possible, the walls must be 
 scraped and frequent irrigations practised. These rules are easily 
 applicable to putrid pleurisies. They may also be employed Lac 
 of pulmonary gangrene. Unfortunately, in the latter case interven- 
 tion is more uncertain, and the individuals operated upon too often 
 succumb, at times tardily, to uncontrollable hemorrhages. 
 
 For the treatment of gangrenes the author has for some time been 
 in the habit of employing peroxide of hydrogen. Many patients suf- 
 fering from erysipelas or a gangrenous phlegmon of the extremities 
 recovered under this procedure. The author prescribes every day a 
 local bath, lasting for an hour, in a 1: 10.000 solution oi potassium 
 
782 INFECTIOUS DISEASES. 
 
 permanganate. The limb is then surrounded with compresses of 
 peroxide of hydrogen. In mild cases this treatment is sufficient. In 
 grave cases a subcutaneous or interstitial injection of peroxide of 
 hydrogen is given morning and evening. The author employs the 
 commercial solution, to which is added an equal volume of a 4: 1000 
 sodium bicarbonate solution. Morning and evening 5 c.cm. or 6 c.cni. 
 sometimes 10 c.cm. of this solution, are injected through several punc- 
 tures all around the sphacelated parts. The injections are given very 
 slowly, so as not to distend the tissues too rapidly by the gas and to 
 avoid penetration into some open bloodvessel. Under this treat- 
 ment putrefaction is arrested and the eschars are soon detached. 
 
 When a gangrenous focus is limited the resistance of the organism 
 is not yet overcome, and consequently operative assistance may be 
 of service. If, however, the lesion is diffuse, if the tissues are simply 
 the seat of a sphacelus in the absence of a focus, the diseased parts 
 cannot be extirpated. Such is notably the case in gangrene of the 
 extremities. When the lesions are extensive but superficial, for 
 instance, as a result of lymphangitis and erysipelas of the lower 
 extremities, if the general state is fairly satisfactory, recovery may 
 be obtained by means of appropriate dressings, by the employment 
 of antiseptics and subcutaneous injections of peroxide of hydrogen. 
 Too often, however, the toxins produced in the necrosed parts give 
 rise to serious symptoms and necessitate amputation of the extremity 
 above the diseased parts. This operation is the only one available in 
 cases of total or diffuse gangrene. Whether the accidents are due 
 to an acute or chronic arteritis or are dependent upon the septic 
 vibrio, there is no chance of recovery except by removing the entire 
 diseased parts. In some cases, however, the apparently healthy 
 tissues are already invaded and the gangrenous process reappears in 
 the operative wound. 
 
 Gangrenes are not always hopeless as regards prognosis. An affec- 
 tion designated by the characteristic name benign gangrene of the 
 bronchial extremities has long been known. We have reported 
 observations of gangrenous mammitis and of curable gangrene of the 
 eyelids which have terminated without causing any serious symp- 
 toms. Lastly, among gangrenous anginas there are some in which 
 the limited sphacelus only slightly disturbs the general condition of 
 the patient. In all these cases the indication is the same as for 
 purulent exudates, and local intervention or antiseptics render the 
 greater service. 
 
THEBAPEUTICB OF INFECTIOUS DISEASES. 
 
 Treatment of Nodular Lesions. The lael form of inflammatory 
 reaction consists in the production of nodules the extenl ol which i- 
 extremely variable. When small, the granulations are generally very 
 numerous and disseminated, and intervention is impo ible. When 
 they are united in a mass they behave as a tumor and require the 
 same fcreatmenl as the latter thai is, extirpation. Finally, when 
 the mass, after having been caseated, is softened, treatment is the 
 same as in cases of suppurating foci, [n both orders of lesions 'I e 
 natural tendency is to open outwardly, bul the opening i tardy and 
 insufficient. We must, therefore, intervene, incise the focus, scrape 
 the walls, extirpate the parts too profoundly altered, and then keep 
 in contact with the locus modifying substances or antiseptics. Among 
 the latter iodine preparations are most commonly employed. 
 
 It is not to be overlooked, however, thai in tuberculosis surgical 
 intervention has sometimes been the point of departure for an acute 
 attack. 
 
 Patients who supported a local lesion fairly well have, in conse- 
 quence of an operation, developed grave symptoms and succumbed 
 to an attack of acute miliary tuberculosis. 
 
 Treatment of Hemorrhages. Hemorrhages occurring in the 
 course of infectious diseases may be divided into two groups: Some 
 are local hemorrhages produced in an inflamed part as a result of the 
 too great intensity of morbid phenomena and the accidental altera- 
 tion of bloodvessels. Hemorrhage may be slight or grave. I ransitory 
 or recurring, but it is generally produced at one point or at a series 
 of points close to each other. The second group comprises hemor- 
 rhages resulting from general modification of the organism. These 
 are not necessarily serious. In a good many infections, small cuta- 
 neous hemorrhages occur which in nowise render prognosis unfavor- 
 able. Such is not the case, however, when multiple and repeated 
 hemorrhages take place. We are then in the presence of the hemor- 
 rhagic forms of infections. To this group belong the putrid fevers 
 of the ancients. In this case the treatment must be directed to 
 modify the general state of the economy, and particularly the 
 chemical constitution of the blood. 
 
 Hemorrhages Due to Local Causes. Hemorrhages arising from local 
 causes may be due to particularly intense inflammation. Conges- 
 tion in this case terminates in rupture. In other instances inflam- 
 mation is mild, but occurs in an individual predisposed To local or 
 general hemorrhages. Lastly, in a third group may be classed 
 
784 INFECTIOUS DISEASES. 
 
 those cases in which a morbid process involves a bloodvessel and 
 ulcerates it. 
 
 Hemorrhages resulting; from too great intensity of a reactionary 
 process are frequent and, as a rule, of little gravity. They may be 
 observed in the skin, in the mucous membranes, and in the organs. 
 Infectious exanthemata and enanthemata, when somewhat intense, 
 produce small vascular ruptures, especially in those parts in which 
 the circulation is more or less embarrassed. When scarlatinal erup- 
 tion is intense small patches of purpura, which have no prognostic 
 value, are often observed, particularly in the lower extremities. Simi- 
 larly, in cases of confluent variola, the pustules upon the legs and 
 hands are sometimes filled with blood; their color changes; they 
 become brownish, and are soon covered with black crusts. These 
 small hemorrhages have no serious significance. They often seem to 
 exercise even a favorable action upon the course of the local process. 
 
 Small hemorrhages are likewise produced in inflamed mucous mem- 
 branes. At times they present a spotted aspect. For example, a 
 mottled red patch occurs in the throat in cases of angina, In some 
 cases, as the mucous membrane is less resistant than the skin, the 
 blood flows out. In the case of coryza, epistaxis is the result; in the 
 case of angina, laryngitis and bronchitis, some spitting of blood; in 
 cases of gastritis or intense enteritis blood appears in the vomit and 
 dejecta. The intestinal hemorrhages occurring at the beginning of 
 typhoid fever must likewise be attributed to the great violence of 
 the infectious process. As is known, their prognosis is generally 
 favorable. Among the hemorrhages which may take place in paren- 
 chymatous organs, those interesting for the therapeutist are ex- 
 pressed by appreciable symptoms. In this connection two organs 
 particularly deserve study: the lungs and the kidneys. 
 
 In cases of bronchopneumonia infarctions may occur in the in- 
 flamed nodules, but they generally remain unnoticed. More exten- 
 sive infarctions give rise to bloody expectoration. In the kidneys, 
 inflammatory hemorrhages are frequent and readily recognized by 
 hematuria. In primary acute and in scarlatinal nephrites, hematuria 
 is often very pronounced and sometimes represents the first morbid 
 manifestation. It may occur, although seldom, in erysipelas. In 
 this instance, however, it lasts longer than in scarlatinal nephritis 
 without having any prognostic gravity. Hemorrhagic nephritis is 
 altogether rare in other infections, except those attended by multiple 
 hemorrhages indicating profound alteration of the organism. 
 
THEBAPEUTI08 OF INFECTIOUS DISEASES. 785 
 
 Now, a few words in reference to hemorrhaged dependent upon 
 individual predisposition. Small eechymo e in the lower extremities 
 in I he course of virions erupl i\ e feven , tnea le . carlatina, or variola 
 occur in subjects having voluminous varices. The eruption of 
 me;isles may also sometimes, here and there, assume an ecchymotic 
 aspect. This occurs particularly in children suffering from whooping- 
 cough and in men I aking copaiba (page 134). [n other instances the 
 hemorrhagic tendency is explained by the state of the subject, who 
 is suffering from a previous hemophilia, or who is under the influence 
 of another infection or intoxication. 
 
 Hemorrhages resulting from the extension of an infect ion- pri 
 into bloodvessels are more important. In most cases this extension 
 is effected so slowly as to permit the formation of a vascular throm- 
 bosis. If, however, the course is rapid or particularly intense, tie 
 vessel is opened, and the hemorrhage thus occurring may be serious 
 enough to cause death, as it may, for example, happen in the third 
 stage of typhoid fever. 
 
 Hemorrhages Due to General Causes. Along with hemorrhages mi-- 
 
 ing from local causes are to be placed those dependent upon a general 
 
 modification of the organism. We shall divide them into three 
 groups. A hemorrhage may represent a symptom of infection . Sue) i 
 is the case in purpura. It may depend upon the lesion of an organ 
 which plays an important role in the coagulal >ility < >f the blood. Such 
 is the case in infectious grave icterus. Finally, and this is the group 
 which we must particularly study, it may result from special viru- 
 lence of the pathogenic germ. They then constitute a particular 
 form of the disease which, in certain cases, differs entirely from the 
 classical type. Thus, hemorrhagic forms of measles, scarlatina, and 
 typhoid fever have been described. These facts are, however, excep- 
 tional, and the most interesting disease from this standpoint is 
 undoubtedly variola. In hemorrhagic variola bloody effusions may 
 occur in any tissue and organ. There may be observed purpura, 
 cutaneous ecchymoses, and bullae, subconjunctival and buccopharyn- 
 geal ecchymoses, epistaxis; gastric, intestinal, uterine, renal, or pul- 
 monary hemorrhages, and extensive bloody infiltrations beneath the 
 skin and in the serous membranes. However multiple they may 
 be, however many parts of the body they may affect, and however 
 grave in character, hemorrhages do not occur at all points of the 
 organism. The alteration of the blood does not. therefore, explain 
 the phenomena completely. We must admit either a predisposition 
 
 50 
 
786 INFECTIOUS DISEASES. 
 
 or some concomitant lesion in the parts which become the seat of 
 the bloody effusion. 
 
 Although hemorrhagic infections mostly belong to the group of 
 general in lections, a localized focus may give rise to toxins sufficiently 
 abundant and active to impregnate the entire economy and cause 
 hemorrhages at points distant from the primary lesion. Dr.Dieulafoy 
 has called attention to facts of this kind by showing that, in certain 
 lesions of the intestine, and notably in appendicitis, noxious sub- 
 stances are elaborated which explain the occurrence of hemorrhages 
 at distant points — for example, hematemesis. 
 
 The preliminary considerations above presented show us how 
 infectious hemorrhages maj 7 be divided theoretically. They establish 
 at the same time that, in the majority of cases, the process is complex. 
 The therapeutist must, therefore, frequently resort to local medica- 
 tion as well as to medication capable of modifying the general 
 state. 
 
 Therapeutic Indications. The first indication is to prescribe rest and 
 immobility. A movement may cause detachment of the clots occlud- 
 ing the open vessels, and thus renew the hemorrhage. In the case 
 of a patient for whom baths have been prescribed, these should be 
 discontinued. If the patient is agitated or delirious, it will be advis- 
 able to prescribe soothing medications, for instance, opium or mor- 
 phine, so as to insure complete quiet. Opium is generally indicated 
 when the patient coughs, even though no bronchial or pulmonary 
 hemorrhages exist, for the effort involved in coughing may detach 
 the clot. It should be remembered that whooping-cough is of itself 
 sufficient to produce hemorrhages. These precautions being taken, 
 it would be well to further prescribe substances which increase the 
 coagulability of the blood. Even when the question is one of local 
 hemorrhages, the dyscrasic modifications resulting from infection 
 tend to maintain or aggravate the flow of blood. For this purpose 
 acid beverages have long been in use. Citric acid or sulphuric acid 
 lemonade may be prescribed. Haller employed in hemorrhagic 
 variola the acid elixir bearing his name and which is nothing else 
 than a dilution of sulphuric acid. Sydenham asserted that sulphuric 
 acid, given in small beer, was the specific medicine for confluent and 
 hemorrhagic variola. At present use is made only of RabePs water 
 (Eau de Rabel) which, as is known, is a mixture of 100 parts of 
 official sulphuric acid, 300 parts of alcohol (at 90° F.), and 4 parts 
 of petals of red poppy. Thus is formed an ethyl sulphate the taste 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 787 
 
 of which recalls that of old brandies. One may prescribe a lemonade 
 
 containing f> per looo of Rabel's water. However, the author's 
 experience with this medication in cases of hemorrhagic variola ha 
 not boon encouraging. 
 
 At present we possess two medicine which seem capable ol 
 increasing the coagulability of the blood: one of them i- calcium 
 chloride. The author has frequently employed thi sail in the treat- 
 ment of hemorrhagic infections and notably in hemorrhagic variola. 
 In two or three days hematurias are arrested, as well as enterorrha- 
 gias and metrorrhagias. In spile of these ameliorations, however, 
 many patients die. As ;i few pal ienls suffering from pustular variola 
 with hemorrhages recovered, and as the medication is inoffensive, the 
 author thinks that it is advisable lo resort lo it in all such C 
 It seems to bo applicable even to all diseases in which hemorrl 
 are due to defective coagulability of the blood. Chloride of calcium 
 thus seems destined to occupy a permanent place in general hemo- 
 static medicines. It is therefore necessary to first determine its 
 posology. This salt is not very toxic; injected into the veins of a 
 rabbit it proves fatal when 100 c.cm. of a 1 per cent, solution, that 
 is, 1 gram of the medicine per kilogram of animal is introduced. 
 This salt, however, is caustic: beneath the skin it produces necrosis 
 and slough. The hypodermic method cannot, therefore, be utilized. 
 It must be introduced by the digestive tract. Either the anhydrous 
 or the crystallized chloride may be prescribed indifferently. It 
 should be remembered, however, that the former is twice as strong 
 as the latter, which, as is known, contains six molecules of water of 
 crystallization. The doses above indicated are those of the crystal- 
 lized chloride of calcium. These doses should be reduced one-half if 
 the anhydrous chloride is prescribed. When dissolved in water or 
 in a julep, this salt has a very disagreeable flavor, recalling that of 
 sea water, leaving in the mouth a metallic taste. It is. therefore, 
 well to prescribe it in some excipient which will mask its bast 
 Rabuteau prescribed 5 grams of calcium chloride in 400 grams of 
 simple syrup and 100 grams of peppermint-water. The daily dose 
 of 4 grams (5j)> which is at times prescribed, seemed to him by far 
 too strong, and he advised the administration of from 20 eg. to 1 gram 
 a day (3 to 15 grains). 
 
 When hemorrhages must be arrested these doses are insufficient. 
 The} r may be considerably increased without inconvenience. The 
 author has begun with giving 4 grams (5j)- Later, when treating a 
 
788 INFECTIOUS DISEASES. 
 
 non-vaccinated child, one year old, he administered from 1 to 11 grams 
 (15 to 22 grains) ; the child recovered. The author then thought that 
 the doses might be increased for adults, and he cautiously gave as 
 much as 12 grams ( o ii J ) m twenty-four hours. This result demon- 
 strates the harmlessness of the medicine which, contrary to the opini< n 
 advanced by some authorities, exercises no purgative action even 
 when given in large doses. At any rate, the author has come to 
 recognize that it is useless to prescribe such considerable quantities; 
 4 grams (oj) a day suffice. The best method of administering the 
 medicine is to dissolve it in a potion containing syrup of bitter orange- 
 peel and including, like the potion of Todd of the Codex, rum and 
 tincture of cinnamon. 
 
 The following may be prescribed: 
 
 Crystallized calcium chloride 4 to 6 grams (3j-jss) 
 
 Syrup of bitter orange-peel 40 " (5.i) 
 
 Old brandy or rum 30 " (gj) 
 
 Tincture of cinnamon 5 " (5j) 
 
 Distilled water 50 " (gij) 
 
 This potion is by no means disagreeable. It may readily be modi- 
 fied by increasing the quantity of rum and, if the taste is unpleasant, 
 by omitting the tincture of cinnamon. A potion without alcohol 
 must be prescribed when a renal lesion is suspected. The syrup of 
 bitter orange-peel suffices to mask the taste, but not as completely 
 as in the formula above given. Chloride of calcium has a by no 
 means less important employment in the treatment of hemorrhagic 
 nephrites. In cases of primary or secondary, and notably of scarla- 
 tinal nephrites, a potion containing from 3 to 4 grams of calcium 
 chloride rapidly diminishes hematuria. In most cases the urine 
 contains no blood at the end of two or three days. In several cases 
 the author noticed the reappearance of hematuria when the medicine 
 was discontinued. As, however, it is admitted that the salts of 
 calcium diminish the coagulability of the blood at the end of a few 
 days, instead of increasing it, the author has constantly suspended 
 its use after four or five days. If necessary, it may again be pre- 
 scribed after an interruption of three or four days. 
 
 Since the contributions of Dastre and P. Carnot, gelatin also is 
 known to have the property of increasing the coagulability of the 
 blood. Experiments upon animals have demonstrated this. The 
 method consists in injecting the substance into the veins. One hesi- 
 tates to apply the method in man. The subcutaneous channel has, 
 
THERAPEUTICS OF INFECTIOUS DISEASES. thU 
 
 therefore, been employed. Physiologists contend, however, that 
 under these conditions the coagulability of the blood i oo1 modified 
 for the reason that the substance U no1 absorbed. The author hat 
 tried subcutaneous injed ion of gelal in in i -\ era! ca e of hemorrhagic 
 variola. In one of the cases the results were excellent, since the 
 symptoms improved and thepatienl recovered. The injected liquid, 
 however, became the starting poinl of a gangrenous phlegmon which 
 raised the entire skin of the abdomen and healed only after a con- 
 siderable period of lime. This suppuration i- explained by the 
 infected condition of the skin in variola. It is interesting to note 
 that the liquid which was discharged by an incision contained a 
 great amount of unaltered gelatin. 
 
 Satisfactory results may he obtained when the chemical modifi- 
 cations of the blood in hemorrhagic infections are discovered. Now 
 that coagulating ferments and fibrinogenous substances are easily 
 prepared, it might be possible to combat a hemorrhagic tendency by 
 means of organic extracts. In this connection the condition of the 
 liver should, perhaps, receive more attention than has hitherto been 
 given to it. At the necropsy of individuals succumbing to hemor- 
 rhagic variola the author has always detected far more profound 
 and extensive hepatic lesions than in cases of confluent variola. It 
 may, therefore, be questioned whether it would not be useful to 
 struggle against the hepatic insufficiency by means of opotherapy. 
 
 Hemorrhages may be combated by producing vasoconstriction. 
 This is obtained indirectly by revulsion, cuppings, sinapisms, and 
 cold beverages. Vasoconstriction may also be effected by certain 
 medicines, chief of which is ergot. The hemostatic action of ergot, 
 which is doubted 03^ so many, seems to me incontestable. It is not, 
 as has been asserted by some, the muscular fibres of the uterus alone 
 that are influenced by it. Nevertheless, ergot seems to the author 
 contraindicated in fevers characterized by a gangrenous tendency 
 in which the nutrition of certain parts seems to be endangered. For 
 it should be well kept in mind that ergot contains substances which 
 of themselves are capable of inducing sphacelus. This medicine is 
 particularly useful when the general state is satisfactory and when 
 the hemorrhage to be combated is confined to one viscus. The 
 author has obtained satisfactory results in the treatment of henior- 
 raghic nephritis, particularly that form folio whig scarlatina. Two 
 grams of Bonjean's ergotin, or 1 gram of Yvon's solution of ergot, 
 or 1 mg. of Tanret's ergotinin may be prescribed. The author gen- 
 
790 ISFECTIOUS DISEASES. 
 
 erally gives one gram of the solution of ergot for three days in suc- 
 cession. This medicine has the advantage of diminishing hematuria 
 and inducing abundant diuresis, which assures organic depuration. 
 Its action appears to the author, however, to be less certain and 
 constant than that of calcium chloride, to which he now gives pref- 
 erence. 
 
 Ipecac is said to favor coagulation by modifying pressure, viz., by 
 reducing it. This medicine is applied particularly in hemoptysis. 
 Ten centigrams are given every half hour, amounting to two or three 
 grams for the twenty-four hours. When the seat of the hemorrhage 
 is accessible, certain substances which promote hemostasis, either by 
 inducing vasoconstriction or by stimulating coagulation of the blood, 
 may be deposited upon it. The former effect may be secured by the 
 application of very cold or very hot fluids. Cold injections of water 
 as well as hot injections at 118.4° or 122° F. (48° or 50° C.) are 
 daily employed against uterine hemorrhages. They may likewise 
 be resorted to for combating nasal hemorrhages. Hot enemas also 
 may be given. When hemorrhages occur on the surface, heat may 
 be applied in the form of a hot-air current. This method is very 
 efficacious. 
 
 Cold may likewise be employed. When the blood proceeds from 
 a deep-seated organ it suffices to apply upon the corresponding 
 region an ice-bag. Fredericq's experiments tend to demonstrate 
 that cold rapidly induces, by reflex action, vasoconstriction of parts 
 subjacent to that which receive the influence. Thus an anemia 
 eminently favorable to coagulation is produced. Certain medicines 
 act as local vasoconstrictors, and among the number is antipyrin. 
 When dusted upon a bleeding mucous membrane, antipyrin often 
 arrests the flow of the blood, and thus renders great service in com- 
 bating nasal or uterine hemorrhages. 
 
 Caustics form a transition between the two groups of hemostatic 
 medicines, since they produce vascular constriction and, coincidently, 
 favor coagulation by precipitating albumins. Hemorrhage may be 
 arrested by touching the diseased part with silver nitrate or by 
 placing upon it a compress saturated with zinc chloride solution. 
 The substance most frequently employed for this purpose is per- 
 chloride of iron; but it is gradually falling into disfavor, because 
 solutions of it induce necrosis, and mortification, and small sloughs, 
 which may hinder evolution of the disease. Among the astringents 
 employed as hemostatics we may also cite alum, which represents 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 7!i| 
 
 the most active principle of Pagliari' heme tatic olution (alum l". 
 benzoin - r )0, water LOO). 
 
 The astringents of vegetable origin eem to be free from the inc 
 veniences inherenl in mineral astringents. The mo > important i- 
 tannin, which may be used in its pure tate, or various substances 
 in which it is found, [njections and irrigations with an effusion of 
 walnut leaves are often employed to arre I lighl hemorrhages. I' 
 is necessary to remember thai tannin, which i iconstrictor in 
 
 small doses, becomes a vasodilator in large 'lose.--, it may be em- 
 ployed m vaginal Injections and enemas. The preparations of rhat- 
 ania may often be substituted for it, the rool containing 13 \<<-r cent . 
 of tannin. In cases of intesl inal hemorrhages in the course of variola 
 the author has obtained excellent result.- by giving large enemas of 
 500 grams (I pint) of boiled salt-water containing 6 grams ,~ 
 extract of rhatania morning ami evening. A new method, iriit i 
 by Dr. Carnot, consists in increasing the coagulability of the blood 
 by spreading gelatin solutions upon the diseased surfaces. Thifi sub- 
 stance possesses the double advantage of heing hemostatic and of 
 representing a sort of aliment for the cells of the organism. It has 
 the inconvenience of being a good culture medium for microbes. 
 Hence, some antiseptic is often associated with it : 0.5: 1000 solu- 
 tion of corrosive sublimate, or a few drops of formol are added to the 
 gelatin solutions, thus rendering them absolutely unassailable by 
 bacteria. To obtain efficacious hemostatic action, it is necessary u> 
 employ a 10 per cent, gelatin solution and sterilize it twice at 212° F. 
 (100° C.) for fifteen minutes each time. Care should be taken not 
 to raise the temperature too high, otherwise the gelatin will lose its 
 characteristic property and become a liquid. These solutions are 
 employed either in local applications upon a bleeding wound or 
 mucous membrane, or in intranasal or intravaginal injections. The 
 author has frequently utilized vaginal injections of gelatin water in 
 the treatment of metrorrhagias which are so common and often grave 
 in variola. Owing to the addition of corrosive sublimate he has 
 never observed the slightest infectious accident. It may. therefore, 
 be concluded that gelatin is an excellent local hemostatic. AYhile 
 the author has expressed some reservation concerning its action upon 
 multiple hemorrhages and regarding the inconvenience, at least in 
 certain cases, of its subcutaneous introduction, there can be no doubt 
 as to its efficacy in local treatment. 
 
 There is another substance which arrests hemorrhages admirably, 
 
7512 INFECTIOUS DISEASES. 
 
 that is, peroxide of hydrogen. A compress saturated with the 
 commercial solution is applied to the bleeding part. The acid con- 
 tained in the liquid favors hemostasis, but renders the treatment 
 somewhal painful. 
 
 Bv means of the various procedures above indicated, it is possible 
 to successfully combat diverse hemorrhages. It is well to remark, 
 however, that this is simply struggling against a symptom, against 
 the result of an infectious disease upon the gravity of which prog- 
 nosis entirely depends. It is certain that in hemorrhagic variola 
 the gravity is not due to the hemorrhages. They simply express 
 the profound intoxication to which the organism succumbs. On 
 the other hand, when a hemorrhage results from a focal lesion, the 
 latter being too intense or too profound, hemostatics are then 
 directed against the very cause of the accidents. All those that 
 we have mentioned are useful, but it is evident that the ideal treat- 
 ment is surgical. The bleeding vessels should be ligatured. Surgical 
 applications, however, are seldom available in the hemorrhages of 
 infectious diseases. The attempts that have been made in typhoid 
 fever are far less rational and efficacious than the operations directed 
 against perforations. The fact is that a large ulcerated vessel is 
 seldom found. In most cases the hemorrhages are multiple or 
 capillary, and operation is evidently out of the question. Surgical 
 intervention is serviceable only in chronic infections. In cases of 
 renal tuberculosis, nephrectomy has often been the only remedy 
 for the persistent hemorrhages. 
 
 [ Therapeutics of Fever. 
 
 Fever constitutes such an essential feature of acute infectious 
 diseases, and, by its course, generally expresses so faithfully their 
 evolution that physicians, mistaking the effect for the cause, have 
 at all times striven to check the febrile movement. Modern advances 
 in pathological physiology enable us to better comprehend the 
 succession of events. Hence, the question whether fever should be 
 combated was laid before the last International Medical Congress. 
 
 In order to give a solution to this important problem of thera- 
 peutics, we must carefully distinguish the febrile process, viz., the 
 increase in the intraorganic chemical acts, from its most apparent 
 result, that is, hyperthermia. To oppose the chemical metabolism 
 going on within an infected organism would be checking a salutary 
 
THEBAPETJTIOB OF INFECTIOUS DISEASES. 793 
 
 reaction salutary ii,i; leasl in mo I case . for, a we ba 1 1 repeatedly 
 stated, the organism does tiol alwaj exactly proportion il 
 to its needs, [t is at limes necei ai to moderate the inten il 
 chemical changes. For this purpose antipyretics render mosl valuable 
 service. This is what occurs especially a1 the end of infection! and 
 during convalescence. Il seems thai the nervou cited 
 
 bythe disease which had jusl terminated, has become too ensitive; 
 the slightest cause gives rise to a febrile reaction which muei be 
 combated, notably by antipyrin. 
 
 In the course of acute infections antipyretics are generally pre- 
 scribed only when they can acl upon the cause of the fever. Specifics 
 respond to this indication. The type of this cla i represented by 
 quinine sails. It is lo-day admitted thai these salts are extremely 
 toxic for the protozoa. They arrest the evolution of Laveran's 
 parasites, and consequently the reaction which characterizee the 
 paroxysm. It would be an error to say thai quinine is an anti- 
 pyretic. It prevents the return of the fever because it arrests the 
 infectious process which causes it. Hence, it produces no net inn 
 against the majority of other hyperthermias. Knonnous dosi 
 quinine have been given to typhoid and tubercular patients withoul 
 lowering their temperature so much as one-tenth of a degree. 
 
 Salicylate of soda seems to act in the same manner. It extin- 
 guishes rheumatic fever because it cheeks the infectious process. 
 It is the same with mercury and iodide, which combat syphilitic 
 fever. To speak of antipyretics in all such cases would be no more 
 exact than to speak of an antipyretic operation when a pyogenic 
 fever is arrested by opening a suppurating focus. The fever is 
 suppressed because the cause of the accidents has been removed. 
 
 Although in the majority of cases it would be a mistake to 
 combat the febrile process, it should not be concluded that it is 
 contraindicated to combat its principal result — hyperthermia. I 
 have endeavored to make it clear that elevation of temperature is 
 the result and sign of increased activity in the chemical acts. A 
 larger amount of heat is produced, but the excess is at the same 
 time dissipated, as is proved by the increased radiation of heat. 
 It is, therefore, indicated to combat hyperthermia by increasing 
 radiation. The best method is by cold bathing. 
 
 Cold and Lukewarm Baths. From the earliest antiquity baths 
 have been given in certain infections. A lukewarm bath was com- 
 monly employed, notably in pneumonia. It was also a lukewarm 
 
794 INFECTIOUS DISEASES. 
 
 bath that was first employed against typhoid fever by Currie in 
 the eighteenth century, and at the beginning of the nineteenth 
 by Chomel, Recamier, and Rayer. Cold water had, however, 
 already been praised by Bartholin, more than two hundred years 
 ago, against pneumonia. The method, however, does not seem to 
 have had great success, for about fifty years ago physicians timidly 
 utilized cold lotions, and sprinkling, and the wet sheet. Few of 
 them ventured to bathe then fever patients. A few attempts were 
 made in favor of cold baths by Giannini (1805), Chomel, Recamier, 
 Jacquez and Leroy. It was, however, only after the labors of von 
 Ziemssen and Brand (1861) that antipyretic balneotherapy entered 
 into therapeutics in a definite manner. 
 
 Yon Ziemssen prescribed baths that rendered the body gradually 
 colder. Bouchard adopted a similar method. In order to avoid 
 the influence exerted upon the nervous system and the vasocon- 
 strictors by cold w r ater, he caused the patient to be placed in a bath 
 the temperature of which is only two degrees Centigrade lower than 
 that of the body. Then he progressively lowers the temperature 
 of the bath to 86° F. (30° C), never below that point. 
 
 By the method which bears his name, Brand produces a violent 
 excitation of the nervous system. Let us consider the rules laid 
 clown by him for the treatment of typhoid fever. They are appli- 
 cable, with slight modifications, to all infectious diseases. 
 
 As soon as the temperature of the patient exceeds 102.2° F. 
 (39° C), he is plunged into a bath at 68° F. (20° C); at times, 
 if the case is grave and the fever intense, into a bath at 64.4° F. 
 (18° C). Certain precautions are to be taken at the same time. 
 Borated vaseline is applied to abrasions and pustules. In order to 
 avoid too violent respiratory disturbance, cold effusions are applied 
 to the face and chest, and the patient is then taken in the arms of 
 the nurse and placed in the bath-tub. The tub should contain 
 sufficient w r ater to cover the shoulders, and it is advisable to renew 
 the water for each bathing. When the patient is in the bath-tub 
 he receives three cold effusions at 50° F. (10° C), at the nape of 
 the neck. These effusions should last three minutes each. Frictions 
 upon the body, except the abdomen, are at the same time to be 
 made. Finally, a small amount of vinous lemonade is to be given 
 to the patient. The bath lasts fifteen minutes. If he should experi- 
 ence chills the patient may still be left in the water, but not for 
 more than two or three minutes longer. When once out of the 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 
 
 water he must be rapidly wiped and then enveloped in blai 
 and warmed by means of hoi water bag applied to the leg and 
 feet. Half an hour later he must be given milk and bouillon. 
 
 [f the patient does uol sleep, or if his leep i agitated, Brand 
 advises, during the intervals of the baths, application of compr< e 
 of water at 50° F. (10° C.) to the chesl and abdomen, to be renewed 
 (^vcry five, ten, or fifteen minutes, according to the intensity of the 
 lover. Tripier and Bouverel prefer large cold poultices upon the 
 abdomen. The bathing, to be efficacious, musl be instituted at 
 as the diagnosis of typhoid fever is made. It there i- any doubt 
 as to the nature of the disease, bathing may still be resorted to, 
 provided it is discontinued if further developments prove the 
 not to be typhoid. When the physician i- called to the side of a 
 patient who has been suffering from typhoid fever for three Wi 
 the cold biitl 1 is useless, and Brand himself then prefers lukewarm 
 baths. 
 
 The baths must be started as scion as the temperature of the 
 patient reaches 102.2° F. (39° C), and the temperature musl con- 
 stantly guide the physician. The temperature must be taken every 
 three hours. When it rises above 102.2° F. (39° C.) a bath is given. 
 When, at the end of three hours, the temperature has not risen to 
 that point, the corresponding bath is omitted. The case is to be 
 managed in this manner until the fever falls below 102.2° F. (39° C.) 
 definitively. At the beginning the temperature rises quite rapidly. 
 The patient, therefore, takes the baths regularly every three hours. 
 As they are not interrupted during the night, he consequently Takes 
 eight baths a day. Later he skips several. In certain cases fever 
 is very intense and does not yield to balneotherapy. Brain 1 then 
 advises, in addition, the permanent employment of cold comprt 3sefi 
 Tripier and Bouveret resort to the wet sheet. Chauffard gives the 
 baths at shorter intervals; Juhel-Renoy gives one every two hours 
 at 59° to 60.8° F. (15° to 16° C). 
 
 In typhoid fever cold bathing has a certain number of contra- 
 indications. In the first place, age is to be taken into account. 
 In children above two years of age it is well to begin with baths 
 at 77° F. (25° C); below that age. lukewarm baths at 86° or 89.6° F. 
 (30° or 32° C.) must be given three or four times in twenty-four 
 hours, each lasting from five to eight minutes. Brand does not 
 advise cold bathing if the patient is more than fifty years old. 
 According to my personal observations. I believe that this limit 
 
796 INFECTIOUS DISEASES. 
 
 should be lowered. It may broadly be stated that, in all infections, 
 cold baths are dangerous above forty years of age. They may, 
 nevertheless, be employed at this age if the circulatory and the 
 respiratory apparatus of the individual are in a perfect state. As 
 a matter of fact, before instituting balneotherapy, the physician must 
 carefully examine these two apparatuses. Valvular lesions of the 
 heart, chronic myocarditis and pericarditis, arteriosclerosis, as well 
 as chronic bronchitis, dilatation of the bronchi, tuberculosis, and, 
 above all, pulmonary emphysema, are contraindications to the 
 balneotherapic method, even to the method of graduated cold baths. 
 Next, the nervous system must be taken into account. In hysterical 
 individuals the bath may provoke an attack. In that case it must 
 be discarded. In certain neuropathic persons it causes fainting or 
 paroxysms of suffocation with a certain degree of asphyxia and 
 cyanosis. In such cases a cold bath is likewise contraindicated. 
 Moreover, some patients have such repugnance to bathing that 
 after they have been given one their temperature is not lowered, 
 but, at times, even a rise occurs. By insisting a little, the physician 
 sometimes may render the bathing method acceptable to such 
 individuals; otherwise, it is better to abandon the balneotherapic 
 procedure. 
 
 These "considerations are applicable to all infections. Here are 
 some concerning particularly typhoid fever : Intestinal hemorrhages 
 and peritoneal manifestations demand absolute rest, and baths should 
 therefore be suspended. Pneumonia is not a contraindication, except 
 when the heart shows signs of weakness. We here touch a much 
 disputed problem. What course is to be followed in cases of myo- 
 carditis? The perusal of classical works leaves the physician in an 
 embarrassed state of mind, for equally competent authorities have 
 advanced contrary views. I believe that, at the beginning, when 
 myocarditis is expressed simply by acceleration in the heart-beats 
 and weakening of the pulse, bathing should still be employed, 
 provided the heart is sustained by medicines such as caffein. Should 
 the slightest fainting occur during the bathing the method must 
 be suspended definitively. If the myocardium seems to be affected, 
 lukewarm bathing may be tried; if it is well borne, the succeeding 
 baths may be given gradually colder. At a more advanced period, 
 when auscultation reveals a bruit de galop, and especially the fetal 
 rhythm, then balneotherapy seems to be a dangerous method, for 
 the reason that the movements of the patient may provoke syncope 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 7!i? 
 
 and sudden death. The writer believe that, under such condition . 
 
 all kinds of baths should be avoided. 
 
 Cold baths do not abridge the duration of typhoid fever, buf they 
 palliate certain symptoms and dimini h the death rate. Tnere it 
 little, if any, stupor; the tongue is moist, diarrhea if model 
 diuresis is more abundant, the appetite i qoI completely lo 
 that the patient takes nourishment with pleasure. Delirium it 
 and, instead of somnolence and the muttering observed in ordinar) 
 cases, the patient enjoys a quid and refreshing sleep after a bath. 
 
 The course of the temperature is profoundly modified. Brand 
 divides it into three periods: the period of resistance, during which 
 the temperature is but slightly modified: then the period of re- 
 mission, and, finally, thai of defervescence. The longer the firsl 
 period lasts, the longer and more rebellious will be the case. If the 
 temperature yields to the first baths, the fever to be deall with will 
 prove to be a mild one. The cold hath also aets upon the circulation 
 and respiration; it stimulates the action of the heart and strengthens 
 the pulse; it diminishes bronchitis and relieve- pulmonary con- 
 gestion. 
 
 As already stated, the death-rate is considerably reduced by this 
 treatment. It is not necessary to cite numerous statistics; it will 
 suffice to state that out of 19,017 observations tabulated by Brand 
 the mortality did not exceed 7.S per cent. In the Bavarian army, 
 in which the method is practised in all its rigor and is instituted as 
 soon as the disease is suspected, the death-rate reaches hardly 
 1 per cent. Although cold baths are at present frequently employed 
 according to the rules of Brand, they have often been modified. 
 Thus, the employment of baths at 82.4° F. (28° C.) has gradually 
 become the current practise in the hospitals of Paris. The baths 
 are given every three hours, when the temperature exceeds 102 ,2 
 or 103.1° F. (39° or 39.5° C). When baths at 82.4° F. (28° C.) 
 are given, it is useless to employ previous cold effusion? or friction 
 during the bath. This method is more readily accepted by the 
 patients, it requires less caution, and gives satisfactory result- ! 
 have recourse to it in benign cases, and I employ no other in the 
 case of children. 
 
 Cold baths do not act merely by abstracting heat. On the con- 
 trary, their action is far more complex. This question has been 
 well studied by Liebermeister. We borrow from him the following 
 
798 INFECTIOUS DISEASES. 
 
 figures, which show the difference of action of a bath at 71.6° F. 
 (22° C.) from that at 82.4° F. (28° C.) : 
 
 
 
 
 
 In a i 
 
 Bath 
 
 U 
 
 lit a 
 
 Bath at 
 
 
 
 
 
 71.6° F. 
 
 (22° 
 
 C). 
 
 S2.4° F. (28° C.) 
 
 In 5 
 
 mii 
 
 Utes the patient 
 
 Loses . 
 
 . 122 calorie 
 
 s. 
 
 33 calories. 
 
 In 10' 
 
 
 " " " 
 
 " 
 
 . 1G5 
 
 tt 
 
 
 44 
 
 " 
 
 In 15 
 
 
 " • " 
 
 " 
 
 . 192 
 
 a 
 
 
 50 
 
 tt 
 
 In 2U 
 
 
 " " " 
 
 
 . 20S 
 
 " 
 
 
 52 
 
 " 
 
 In 30 
 
 
 ,1 u tt 
 
 " 
 
 . 342 
 
 " 
 
 
 56 
 
 tt 
 
 If the principal object was to abstract heat, the bath at 82.4° F. 
 (28° C.) should be rejected without hesitation; but at present the 
 influence of hyperthermia is no longer so much dreaded. It is known 
 that the disturbances and lesions formerly attributed to high temper- 
 ature are in most cases due to toxins. Cold baths produce satis- 
 factory results, not merely by lowering the temperature, but exercis- 
 ing a favorable influence upon the various apparatus of the entire 
 organism. First of all, the nerve terminations of the skin are influ- 
 enced by the bath, and their dynamic modification reaches the 
 centres. The very cold bath thus gives rise to a violent excitation ; 
 the lukewarm bath has a sedative action . In both cases the function 
 of the nervous system is regulated, and amelioration in the activity 
 of all the tributary organs results. The heart largely participates 
 in the benefit of this happy influence. In the case of cold baths, 
 the cutaneous vasoconstriction raises the blood pressure, and thus 
 modifies the activity of the myocardium. Circulation is, therefore, 
 favored in the lungs and kidneys. Hence, diminution in pulmonary 
 congestion and increase in diuresis, as well as greater activity in 
 general oxidation, result. All these changes explain how the bath 
 diminishes the intoxication of the organism. It accomplishes this 
 by regulating nutrition, by favoring the action of the liver and the 
 emunctories, notably the kidneys. The experiments of Drs. Roques 
 and Weil demonstrated that the urinary secretion is not only 
 increased in amount but also in toxicity. Thus a great quantity 
 of toxins is carried away and the organism purified. 
 
 Brand's method, which was at first applied to typhoid fever, is 
 now employed in a great number of infections. The baths may be 
 given whenever the temperature is very high, not so much because 
 of the hyperthermia as for the intensity of the morbid phenomena 
 which produce and entertain it. The baths must likewise be resorted 
 to when the nervous system is profoundly affected, when the pulse 
 is very rapid and the urine scanty. The physician must always 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 799 
 
 be guided by the gravity of the phenomena in choosing bel 
 Lukewarm, 82.4° F. (28° C), and cold baths, 69° or 64 1 I 20 
 18° C). The latter are especially indicated when the nei 
 system is profoundly affected, whether the phenomena indicate 
 depression, or, on the contrary, too violenl excitation . juch as 
 delirium tremens, are present. Finally, the ati factorj re ultt ob- 
 tained by cold baths in the treatment of cerebral rheumatism I 
 long been recognized . 
 
 En our hospital we employ the bath at 82.4 I. .'- I fre- 
 
 quently at a lower temperature, in case oi carlatina and erysipelas 
 whenever the temperature remains longer than usual around or 
 above 104° F. (40° ('.). This treatmenl ie let frequently available 
 in measles, for the gravity of the latter disi ase depends simply upon 
 pulmonary complications. We Bhall again refer to this subject. 
 
 Balneotherapy is nlso indicated in measles, scarlatina, and variola 
 when the eruption is not well developed. The author prefer.- warm 
 baths at 89.6° or 93.2° F. (32° or .34° C), and in grave variola 
 or measles, mustard baths. At the beginning of all eruptive fevers 
 we frequently see serious general manifestations while the eruption 
 is as yet hardly noticeable. The eruption does not come oul as 
 rapidly and with the same intensity as in fortunate cases. A few- 
 baths hasten the appearance of the exanthema and palliate the grave 
 symptoms. In variola also, as we have already stated, excellent 
 results are obtained by the same method. The author gives luke- 
 warm baths to which some corrosive sublimate or naphthol is added. 
 Notwithstanding its lesions, the skin bears this mode of treatmenl 
 well. It exercises a marked action upon the pyogenic bacteria which. 
 at a certain period of evolution, invade the pustules. 
 
 Among the infections for which baths are available there are three 
 which require special attention. These are scarlatina, pneumonia, 
 and erysipelas. Hyperpyretic scarlatina is generally described as the 
 type of malignant scarlatina. If we refer to our statistics we find 
 that the frequency of this form, at least in the adult, lias been some- 
 what exaggerated. We have received in our wards, especially in 1 899, 
 grave cases, several of which rapidly ended in death. In the majority 
 of the cases, however, the temperature was not extremely high. It 
 is not, therefore, safe to be guided exclusively by the course of the 
 temperature. The general state of the patient furnishes more reli- 
 able indications. The general state likewise directs the therapeutics 
 of pneumonia. All grave cases must not. however, be indiscrimin- 
 
800 INFECTIO US DISEASES. 
 
 ately treated by baths. This medication must not be resorted to in 
 the aged or in arteriosclerotic individuals, or those suffering from 
 heart lesions and Bright 's disease. These are substantially the same 
 contraindications which we have pointed out with regard to other 
 diseases. The reason we emphasize the point is that it is precisely 
 under these conditions that the gravest cases are observed and that 
 the physician is tempted to prescribe baths. What is more peculiar 
 to pneumonia is the danger of giving rise to collapse in case both 
 lungs are involved. In fortunate cases, under the influence of the 
 bath, respiration becomes easier, expectoration more profuse and 
 free, cyanosis disappears, and diuresis is more marked; at times a 
 veritable polyuria is produced. Hence the termination of the disease 
 differs from that observed when the evolution is left to itself. The 
 crisis is replaced by a slow defervescence, which is probably clue to 
 the fact that the toxins, far from being accumulated during the 
 disease, to be suddenly rejected at the moment of the termination, 
 have been eliminated in a continuous manner. 
 
 Baths are currently employed in the treatment of bronchopneu- 
 monia. In this case cold baths have been almost entirely abandoned, 
 for they readily give rise to collapse, especially in young children. 
 Graduated cold baths may be used. They may be given at two 
 degrees lower than the temperature of the patient and progressively 
 lowered to 82.4° F. (28° C). Their duration must not exceed five 
 minutes. More frequently lukewarm mustard baths are prescribed, 
 especially for children. Finally, since the contributions of Dr. 
 Renaut, warm baths at 100.4° F. (38° C.) are often employed. The 
 child remains in it from ten to twenty seconds, and during all this 
 time, cold compresses are applied to the head. The baths rapidly 
 palliate the bronchial manifestations, but they produce hardly any 
 effect upon the pulmonary lesions. Their action upon the general 
 state is excellent, but the hot bath is somewhat depressing. It must 
 be avoided in adynamic cases or when cardiac disturbances are 
 present. 
 
 The author frequently employs lukewarm baths in the treatment 
 of erysipelas. In cases of circumscribed erysipelas of the face unat- 
 tended by grave general phenomena the bath is useless. In spite 
 of the temperature of 104° F. (40° C.) defervescence is rapidly pro- 
 duced. If, however, fever persists, if certain alarming manifesta- 
 tions, such as adynamia, delirium, and agitation are observed, or if 
 the inflammatory lesion spreads, a bath at 82.4° F. (28° C.) should 
 
THERAPEUTICS OF INFECTIOUS DISEASES. -■.] 
 
 I, hen be given every three hour, whenever the temperatun 
 L03° F. (39.5° C). 
 
 In cases of wandering erysipelas, bath al 82.5' I ' ' are 
 likewise indicated. They should be given ; tematically every three 
 hours, regardless of fluctuations in the temperature, for in * 
 wandering forms very wide oscillation are observed, and even inter- 
 mittent types are sometimes encountered. Bathi are similarly 
 cessful in delirium. The author generally employs lukewarm baths. 
 Morning and evening he prescribes a bathal 93.2 I 34 C), which 
 lasts from thirty i<> forty-five minutes. Its sedative effecl upon the 
 nervous system is very remarkable. Warm bathe succeed very well 
 in erysipelas of children :m<l of the newborn. In the latter, regard- 
 less of the seat of the lesion, three daily baths al 89.5 oi 93.2 I . 
 (32° or 34° C), lasting six or eigbl minutes, constitute the 
 method. 
 
 It is well to once more recall the danger of baths for individuals 
 above forty years of age. As erysipelas is a disease occurring mainly 
 after this age, the author believes the following precept should be 
 emphasized: lukewarm baths may be given between the agi 
 forty and fifty years; after fifty years they should not be prescribed 
 except for robust individuals presenting no lesions of the circulatory 
 or respiratory apparatus. 
 
 Chemical Antithermics. Chemical antithermics ac1 in three ways: 
 they exercise a sedative action upon the nervous system ; they dimin- 
 ish the protoplasmic activity of the cells: they modify the function 
 of the red blood corpuscles. Of these three actions the firsl is contest- 
 able; it results simply from the fact that antithermics are. as a rule, 
 analgesics. The second is bad, for increased functional activity of 
 the cells represents a necessary reaction which should be modei 
 only under certain circumstances. The third is worse, for it consists 
 in the formation of methemoglobin, which causes cyarn »sis. This last 
 influence is particularly manifest when kairin, thallin. or acetanilid 
 (antifebrin) are employed. These products are. therefore, ab si 
 completely abandoned, and only three antipyretics are at present 
 made use of: quinine, antipyrin. and salicylic acid and its derivatives. 
 
 The successes obtained by quinine in the treatment of malarial 
 fevers, in which it acts as a specific, have too easily led to the belief 
 that this substance is a universal febrifuge. In typhoid fever as well 
 as in erysipelas, pneumonia, and variola, the author has repeatedly 
 observed that large doses of quinine salts may be administered with- 
 
 51 
 
802 IXFECTIO US DISEA SES. 
 
 out producing any noticeable change in the temperature. One gram 
 and a half or two grams are required in typhoid fever in order to effect 
 a reduction of temperature. In view of these failures, some authors 
 have stated that quinine regulates rather than lowers the tempera- 
 ture. Its administration must, Therefore, be reserved for those cases 
 of fever which present wide oscillations — i. e., fevers of an intermit- 
 tent type, like malarial fever. This remark is correct for some cases. 
 Thus, for instance, in typhoid fever, after having remained at a 
 certain point during the stationary period, the temperature often 
 presents wide oscillations at the moment of termination. When 
 fever is continuous the author has never found quinine efficacious. 
 At the time of the oscillations the administration of this alkaloid 
 appeared in some cases to bring the temperature to the normal. 
 Hence, the author believes that it is useless to prescribe quinine 
 during the stationary period. This medicine should be reserved for 
 the third period. If the temperature then presents an amphibole 
 stage and does not return to the normal, quinine should be prescribed 
 in decreasing doses for three days in succession, four or five hours 
 before the expected return of the paroxysm. The author prescribes 
 1 gram the first day, 75 eg. the second, and 50 eg. the third day. 
 It is to be borne in mind, however, that this method is not infallible 
 and that quite often fever does not yield to the action of quinine 
 even at this period. 
 
 The author has likewise been convinced of the inefficacy of quinine 
 in the treatment of hectic fever of tubercular subjects and of the 
 fever of erysipelas, even when its course assumes the intermittent 
 type, falling to 98.5° F. (37° C.) in the morning, to rise to 104° F. 
 (40° C.) in the evening. Lastly, in symptomatic intermittent fevers 
 quinine at times lowers the temperature. The result is not very 
 marked or very durable, however, so that this medicine may serve 
 to make a differential diagnosis between symptomatic intermittent 
 and malarial fevers. 
 
 Antipyrin has a far more marked influence upon the febrile pro- 
 cess. It often lowers the temperature; but it accomplishes this by 
 diminishing oxidations, consequently, by hindering one of the reac- 
 tionary procedures employed by the organism. Hence, its use is but 
 exceptionally indicated. The author finds only a few cases in which 
 this medicine is serviceable. The first is influenza. Antipyrin 
 must be given mixed with quinine. The author prescribes 1 or 2 
 grams of the first with 75 eg. or 1 gram of the second. When 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 
 
 administered at the beginning of influenza bhi medication often 
 
 succeeds in arrest ing the di ea e. I 1 i almo i a pecific. Again, 
 those tubercular patients who suffer from fever are often benefited 
 
 by the use of antipyrin, al lea I in tho • r ■ • in which it does not 
 cause too much sweating. Its action upon the fever of tubercular 
 subjects is so marked thai Dr. Landouzy thinks, with good reason, 
 that it may throw lighl upon a doubtful diagnosis in acute c 
 When the physician is not sure whether be is dealing with a typhoid 
 lexer or an acute miliary tuberculosis, the administration "t anti- 
 pyrin, if it be followed by a well-marked defervescence, will lead him 
 to assume Mia.1 (license is tubercular. At any rate, antipyrin acta 
 in all forms of tubercular fever, even againsl hectic fever. It - acl ion, 
 however, is transitory. The author has seen tubercular cases in which 
 no treatment had succeeded in lowering the temperature, become 
 completely apyretic under the influence of this medicine. At the end 
 of four or five days, however, fever reappeared, and, although the dose 
 was increased to 3 and I grains in twenty-four hours, the effect 
 seemed completely exhausted. Although transitory and in nowise 
 affecting the process itself, hut only one of its effects, the action of 
 antipyrin seems to the author sufficiently marked to give the sub- 
 stance a permanent place in the therapeutics of tuberculosis. 
 
 While antipyrin is useless in the stationary period of infections, it 
 renders true service at the terminal period and during convalescence. 
 In many cases fever survives the disease. The morbid symptoms 
 seem to have disappeared, but the temperature does not become 
 normal. This fact is due to the reactionary susceptibility of the 
 organism induced by the infection. Under these conditions the 
 organic combustions exceed the requirements of the system. Anti- 
 pyrin, by modifying oxidations, reduces metabolism to a degree cor- 
 responding to the wants of the economy. Likewise, during conval- 
 escence the slightest cause suffices to raise the temperature. A febrile 
 paroxysm may supervene, even without any noticeable cause. 
 Antipyrin is then indicated, inasmuch as this fever of convalescence is 
 dependent upon the same mechanism as the lingering fever at the end 
 of infections, and should be treated in the same maimer. 
 
 A new antipyretic, pyramidon, has recently been praised, and may 
 be employed under the same conditions as antipyrin. but in smaller 
 doses. This substance has given satisfactory results in some of the 
 author's cases. Its advantage consists in its very quick elimination. 
 Thirty and fifty centigrams of pyramidon may. therefore, be pre- 
 
804 ISFECTIO US DISEASES. 
 
 scribed every three hours, and as much as two grams a day without 
 fear of any untoward cumulative effects. 
 
 Salicylic acid and its derivatives — salol, salophen, salipyrin, and 
 aspirin — are often classed with antipyretics. Salicylate of soda lowers 
 the temperature in cases of rheumatic polyarthritis, but it is the 
 specific of this infection. On the other hand, it is without effect in 
 infectious pseudorheumatism. It may, therefore, serve the purposes 
 of differential diagnosis. 
 
 Salicylate of soda and salol owe certain antipyretic virtues to their 
 antiseptic properties. Hence, these medicines may be employed to 
 combat certain symptomatic fevers, notably those related to suppu- 
 rations of the biliary passages or the urinary apparatus. In these 
 cases, however, the process is not a truly febrifuge action. The 
 medicine produces its effect bjr acting upon the cause. Its adminis- 
 tration is, therefore, clearly indicated and realizes an etiological 
 medication. 
 
 Finally, by a mechanism as yet illy elucidated, guaiacol when 
 applied to the skin has the interesting property of lowering the tem- 
 perature. It acts so powerfully that, if precautions are not taken, 
 collapse may occur. This method is available particularly in the 
 treatment of tubercular fever. 
 
 Conclusion. From the foregoing brief study we may conclude 
 that there are no good antipyretic medicines. At all events, the 
 dangers and inconveniences of fever have been much exaggerated. 
 In many cases to arrest the febrile process would be to harm the 
 patient. 
 
 The true antipyretic is that which suppresses fever, not by dis- 
 turbing the reactionary movement of the organism, but by acting 
 upon the cause of the febrile process. This is precisely what is real- 
 ized by specifics — quinine in malaria, mercury and iodides in syph- 
 ilitic fever, sodium salicylate in rheumatism, the insoluble antiseptics 
 in fevers of intestinal origin, and antiseptics or antitoxins introduced 
 into infected foci. These are substances which deserve to be con- 
 sidered as antipyretics of predilection. They act by combating the 
 cause of the morbid process, while most of the febrifuges, by modi- 
 fying the reactionary mechanism, hinder nature's work. Balneo- 
 therapy alone represents a natural medication, for it simply favors 
 dissipation of heat, which is already increased by the disease. At the 
 same time baths act upon the principal apparatus of the economy. 
 Hence, they are now currently used and are applicable to a great 
 
THEBAPEXJTIOB OF INFECTIOUS DISEASES. 805 
 
 number of infections. Being given lukewarm or cold, according to 
 circumstances, the bath is the only true antipyretic thai may be 
 
 prescribed. 
 
 Venesection. 
 
 We are far from the epoch when blood-letting wan j tematically 
 
 practised in fevers, when it was imagined thai acute di ea i could 
 be checked by repeated abstraction of the vital Quid. At presenl 
 this method is seldom resorted to in the treatmenl of infectious 
 diseases. II is employed only in pneumonia or in certain complica- 
 tions. Wo nmsf, ilierefore, briefly study its influence upon the 
 organism and its possible indications in infections. Withoul present- 
 ing the history of the physiological effects < I' blood-letting, which is 
 still obscure on cerlain points, it will suffice to refer fco the acquired 
 results. An easily foreseen first effect is a reduction in blood pressure. 
 This phenomenon is produced as soon as the vein is open. Tension 
 rapidly decreases, to again rise slowly when the How is arrested, and 
 returns to a figure somewhat below that observed al the beginning. 
 In this respect successive blood-lettings act less and less enei e 
 cally. Coincidently, according to Marey's law, the pulse becomes 
 more rapid and weak. If, however, arterial tension is very consid- 
 erable and venous stasis very marked, the pulse becomes fuller. The 
 red blood corpuscles diminish in number, but this first phenomenon 
 is followed by a very marked increase in the hematoblasts. This 
 second result, noted by Dr. Hayem, is in perfect harmony with the 
 researches which have been pursued on the hematopoietic organs, 
 demonstrating their increased functional activity. After the bleed- 
 ing the cells proliferate in order to repair the losses of the organism. 
 and, as always, compensation exceeds the primary effect. The slight 
 leucocytosis which supervenes in most cases is probably produced 
 by the same mechanism. The diminution of the blood mass has two 
 important consequences: it facilitates the circulation in parts which 
 are overloaded with blood and relieves passive congestions, with the 
 result that the functions of the organs are better fulfilled. The effect 
 is particularly appreciable in the lungs. At the same time, an osmotic 
 current is established from the tissues toward the bloodvessels. The 
 interstitial fluids pass into the circulation. If they are toxic, their 
 action upon the organism may be dreaded, and. in fact. Lisfranc 
 rejected blood-letting whenever a purulent or putrid focus existed. 
 If, however, elimination is easy, blood-letting favors the passage into 
 
806 INFECTIOUS DISEASES. 
 
 the blood of substances deposited in the interstitial plasma, and thus 
 promotes disintoxication of the organism. Blood-letting acts the 
 better the easier the work of the heart is rendered under its influence, 
 and, consequently, the urinary secretion is increased. As a matter 
 of fact, experiments have demonstrated that diuresis is increased in 
 consequence - of blood-letting. Since we are speaking of poisons, it 
 is well to remark that blood-letting is one of the best means for freeing 
 the organism from them. With good reason, Prof. Bouchard has 
 laid stress on this point. He notes that a blood-letting of 32 grams 
 eliminates from the organism 0.5 gram of extractive matters. 
 In twenty-four hours the urine eliminates 8 grams of such matters. 
 Tli is small loss of blood thus throws out of the body the one-sixteenth 
 part of the poison accumulating in one day when urinary secretion 
 is suspended. This result seems still greater when it is remembered 
 that 280 grams of intestinal fluid or 10 quarts (9 litres) of sweat are 
 required hi order to produce the same effect. 
 
 By modifying blood pressure, blood-letting is followed by dilata- 
 tion of the capillaries and, consequently, a more active irrigation of 
 the tissues. The result is a favorable modification in nutrition. In 
 fact, the urine of twenty-four hours eliminates more urea, more phos- 
 phoric acid and extractive matters (Lepine). The same influence 
 may be found by studying the organic apparatus ; the nervous system 
 becomes more active, and respiration easier and deeper. A last effect 
 of blood-letting is a modification in the temperature. Under its in- 
 fluence temperature is lowered, and this effect is the more marked as 
 calorification is increased. The thermometer has sometimes marked 
 one or two degrees less after blood-letting. Unless, however, abun- 
 dant and repeated bleedings are practised, the effect is transitory; 
 the temperature soon rises, and at times exceeds the former 
 degree. 
 
 Let us now apply these data to infectious diseases. The indica- 
 tions may be formulated in the following manner: Blood-letting is 
 indicated for combating excessive hyperthermia. Congestion in the 
 venous system embarrasses cardiac contraction and gives rise to 
 passive congestion in the lungs, kidneys, and brain. The result is a 
 profound and rapid intoxication of the organism, especially if renal 
 insufficiency coexists. 
 
 Blood-letting is contraindicated, even under the foregoing condi- 
 tions, in children, the aged, and debilitated individuals. In other 
 words, the advisability of blood-letting is to be considered only as 
 
THERAPEUTICS OF TNFE0TI0U8 DISEASES. 807 
 
 regards vigorous adults, especially tho epre enting whal the ancient* 
 designated under the terra plethoric temperament. 
 
 Let us now consider a determined infection, the only one, perl 
 in which blood-letting is still quite frequently employed i.e., 
 pneumonia. formerly, blood-letting wa resorted to j tematically. 
 Tommasini, of Bologne, practised ;is many as twenty blood-lettings 
 of from loo grams to 500 grams each. He thus drew ten quarU 
 (nine litres) of Mood. Broussais and Bouillaud followed an analo- 
 gous method. Ai presenl there is general agreemenl thai blood- 
 letting does not check pneumonia : ii does not even abridge its course, 
 Out, it, improves certain symptoms. It is indicated in all vigi 
 adults in whom lexer is intense and dyspnea is troublesome and in 
 whom an extensive focus surrounded by ;i vasl zone of hyperemia 
 and edema is found. It is likewise indicated when the patienl i- 
 cyanosed and (lie righl hear! is dilated; also when venous stasis 
 
 affects (lie bruin, giving rise to somnolence or ;i semicomatose state. 
 Iii this case, blood-letting brings immediate relief; respiration be- 
 comes freer, deeper, and shorter; the pulse is strengthened, the ner- 
 vous disturbances diminish, and in several cases an amelioration in 
 cardiac manifestations and increased diuresis are clearly observed. 
 
 Blood-letting has been practised in all infectious diseases. Typhoid 
 fever, eruptive fevers, erysipelas, inflammations of the serous mem- 
 branes, and especially acute articular rheumatism have been treated 
 by blood-letting. Dr. Du Castel thinks that this method may render 
 service in variola when very marked phenomena of cerebral stasis 
 are present. This particular case excepted, blood-letting is indicate. I 
 in infectious diseases when intense pulmonary and renal disturbances 
 are observed. It may likewise be available in other localizations in 
 the viscera or serous membranes. In this case, however, local deple- 
 tions and wet cuppings are mostly employed. 
 
 Blood-letting is, therefore, reserved for those cases in which 
 intense pulmonary congestion hinders hematosis and embarrass - 
 the function of the right heart. It becomes altogether urgent in 
 cases of acute pulmonary edema. In certain fever cases, especially 
 when renal lesions are present, pulmonary edema may rapidly 
 appear and, at times, cause death within a few minutes. This 
 dangerous manifestation is observed particularly during convales- 
 cence in the course of scarlatinal nephritis. This is one of the most 
 formal indications for blood-letting, as the procedure gives mar- 
 vellous results against this visceral manifestation. 
 
808 INFECTIOUS DISEASES. 
 
 When the renal lesion influences the nervous system the indication 
 for blood-letting is not any less clear. It is likewise during con- 
 valescence from scarlatina that uremic accidents involving the brain 
 are observed and command bleeding. While this method is service- 
 able against the symptoms of chronic nephritis, it is particularly 
 indicated in acute nephrites which manifest a natural tendency 
 toward recovery. It suffices to assist the organism a little in order 
 to avoid grave manifestations. 
 
 The knowledge of the role played by intoxication in the production 
 of infectious symptoms leads to the question whether it would not 
 be advisable to practise blood-letting in certain grave cases. The 
 amount of poisons impregnating the economy would thus be dimin- 
 ished. The suggestion is evidently rational. It may, however, be 
 objected that the loss of blood would weaken the patient. The 
 question is again laid before us to-day. We know, in fact, the 
 marvellous results of salt-water injections in the treatment of infec- 
 tions. Some authorities have, therefore, proposed to combine the 
 two methods. The idea is perfectly reasonable, and the disadvantages 
 of venesection are thus offset by saline infusion. 
 
 Injections of Artificial Serum. 
 
 Intravenous or subcutaneous injections of artificial serum are 
 daily employed at present in the treatment of the most varied 
 infections. While there is general agreement as to their usefulness, 
 their mode of action is still a subject of controversy. Drs. Dastre 
 and Loye, who were the first to transfer the question to experimental 
 ground, suppose that salt-water injections realize lavage of the 
 organism. It has been objected, however, that in hydremic animals 
 the renal secretion is profoundly modified. The urine is an aqueous 
 fluid which, in certain cases, carried less extractive matters than it 
 would under normal conditions. Some experimental investigations 
 have confirmed this conclusion by demonstrating that infected or 
 intoxicated animals upon which lavage of the blood is practised die 
 before the controls. It is to be noted that the problem is far more 
 complex than seems at first view. When salt-water is injected 
 beneath the skin or into the veins quite different effects are pro- 
 duced. The amount of fluid contained in the vessels is modified. 
 Contrary to what might be expected, the blood pressure varies 
 little, at least if it was normal. We must, therefore, presume that 
 either vasomotor modifications or some eliminations have rapidly 
 
THERAPEUTICS OF INFECTIOUS DISEA8E8. 809 
 
 taken place. In the latter instance, if a portion of the fluid i 
 jected by the emunctories, another portion i deposited in certain 
 tissues, and modifies the nutrition of the organ] en, and con equently 
 produces changes in the activity of vrariou pari . A a thattei of 
 fact, experiments have demonstrated thai the responsive aptitude 
 of the nervous system is considerably increased. Thie modification 
 is immediate; it supervenes immediately after the injection. A.1 
 the same time, however, the nutritional modification* are foil 
 by changes in the histological structure of certain tissues. Thifi 
 is readily recognized by studying the bone-marrow. 
 
 Influence of Injections of Artificial Serum upon Absorption. The 
 first question is whether injections of salt-water modify the absorp- 
 tion of poisons deposited beneath the skin or in the alimentary 
 canal. Magendie took up this problem. He introduced a poison 
 into the pleura after having practised blood-letting. The disturb- 
 ances were manifest at the end of thirty seconds, while in an intacl 
 animal they did not appear until two minutes after. On the other 
 hand, when he injected one or two quarts (litres) of water into the 
 veins the symptoms were then inure tardy; they often did not appear 
 when two quarts were introduced. When, however, blood-letting 
 was practised upon this hydremic animal the toxic manifestations 
 developed as the blood was flowing. The experiments of Delbet 
 likewise established that intravenous injections of salt water prevent 
 the absorption of strychnine introduced into the peritoneum. More 
 recent experiments pursued by Dr. Ghassevant also demonstrated 
 that such injections retard and attenuate the action of strychnine 
 introduced beneath the skin. Taking up this question, I learned 
 that salt-water effectively retards the absorption of strychnine. 
 The fluid was injected into rabbits by the intravenous route, at a 
 temperature of 102.2° F. (39° C), in amounts of 3 to 4 c.cm. per 
 minute per kilogram of animal. The amount introduced varied 
 from 3 to 228 c.cm. per kilogram. Five minutes after the salt- 
 water injection the animals received subcutaneously from I I 
 mg. of strychnine sulphate. The injections of salt-water in doses 
 of 3 to 70 c.cm. per kilogram did not greatly modify the resistance 
 of the animals; at times they increased it. and at other times they 
 diminished it. "When, however, considerable quantities were intro- 
 duced, that is from 166 to 228 c.cm. per kilogram, the symptoms 
 were delayed and less marked. Thus. 1 mg. killed a rabbit within 
 eighteen to thirty-one minutes: while it takes half an hour to kill 
 
810 IXFECTIO US DISEA SES. 
 
 an animal having previously received 210 c.cni. of salt-water per 
 kilogram. By diminishing the dose of the poison we observed no 
 disorder whatever. In one rabbit 7 mg. produced no disturbance, 
 not even an exaggeration of the reflexes, while two other rabbits 
 which received the same 1 amount of strychnine per kilogram, had 
 intermittent convulsions extending over a period of seven or eight 
 minutes; then the animals recovered, although for thirty to forty 
 minutes they retained a very marked exaggeration of the reflexes. 
 
 When strychnine is injected into the veins instead of beneath 
 the skin, the results are different. The animals which received salt- 
 water reacted far more rapidly and energetically, and died before 
 the controls. This result demonstrates that injections of salt-water, 
 while retarding the action of strychnine injected beneath the skin, 
 do not act by diminishing the sensibility of the animals. It must, 
 therefore, be admitted either that they hasten elimination or that 
 they hinder absorption. By injecting strychnine into the veins at 
 a very slow rate, so as to introduce the convulsifying dose in an 
 hour and a half, elimination should be effected still more easily 
 than is the case in subcutaneous injections. The animals should 
 not present any disorder. Experiments having given the contrary 
 result, I concluded that the role of elimination is insignificant. 
 Injection of large quantities of salt-water into the veins retard and 
 diminish strychnine intoxication because they hinder absorption. 
 
 Here, therefore, is a first result which must be taken into account 
 for therapeutic indications. The result should not, however, be 
 generalized. What is true of alkaloids is not applicable to microbic 
 toxins. Enriquez and Hallion demonstrated that previous injections 
 of salt-water in nowise prevent the absorption of diphtheritic toxins 
 injected beneath the skin. 
 
 Influence of Injections of Artificial Serum upon Elimination. 
 What is the influence of intravenous injections upon renal elimina- 
 tion? Numerous researches have been pursued on this subject. 
 Dastre and Loye, who have well studied the method from an experi- 
 mental standpoint, practised lavage of the blood. The attempts, 
 however, which were made to save the intoxicated or infected 
 animals generally gave no results. The animals thus treated died 
 more rapidly than the controls. By studying the urine of animals 
 having received such amounts of salt-water as to double the blood 
 mass, Carrion and Hallion learned that while the amount of water 
 excreted increases, the amount of matters eliminated, except that of 
 
THERAPEUTICS OF TNFE0TI0U8 diseases. nil 
 
 sodium chloride, is mailer than normal. Sodium chloride i substi- 
 tuted in the mine for other materials) il doe nol carry them away. 
 These results account for the failure of attempt* ol experimental 
 therapeutics. 
 
 These results, however, should no1 !"• ha Hi', generalized. 
 matter of fact, I have obtained differenl result* by studying the 
 elimination of two substances which are ea il) detected in the urine 
 — ferrocyanide of potassium and Bulphindigotate of soda. 
 
 In a first series of experiments, rabbits received through a vein 
 of the ear I c.cm. of a 1 : 20( I solution (2 centigrams) of ferro- 
 cyanide of potassium. The injection lasted a minute. Then an 
 effort was made to discover al what moment the urine gave the 
 characteristic blue color with perchloride of iron. In order to deter- 
 mine this, we collected every minute a few drop- of the urine either 
 by means of ;i catheter or by compressing the bladder through the 
 abdominal wall. By experimenting upon sis normal rabbits we 
 discovered the presence of ferrocyanide in the urine ;it the end of 
 ten, eleven, thirteen, fourteen, sixteen, and seventeen minutes 
 thirteen minutes on an average. In lour rabbits into which we 
 injected salt-water before the introduction of the ferrocyanide we 
 obtained the following figures: seven minutes in a first rabbit 
 having previously received 62 c.cm. of salt-water per kilogram; -i\ 
 minutes in a second rabbit having received 100 c.cm.: eight minutes 
 in two others, one having received 133 and the other 160 con. per 
 kilogram: the average is seven minutes. The differences are. there- 
 fore, very clear. The previous injection of salt-water caused the 
 ferrocyanide to appear in the urine twice as rapidly as in the controls. 
 
 It is very difficult to determine at the end of what time elimination 
 is completed, for the ferrocyanide diminishes little by little, and a 
 moment arrives when reaction with perchloride of iron becomes 
 extremely doubtful. Nevertheless, here are figures presenting a 
 comparative value. In three normal rabbits reaction discontinued 
 respectively at the end of tour hours, four hours and forty minutes, 
 and five hours. In three rabbits which received salt-water after the 
 injection of the ferrocyanide reaction ceased: in the first one. which 
 had received 62 c.cm. per kilogram, at the end of four hours: in 
 the other two, which had received each 100 c.cm. at the end of 
 three hours and forty minutes and three hours and thirty minutes, 
 respectively. Thus, it may be stated that, on an average, elimina- 
 tion lasts four hours and thirty-three minute? in the controls, and 
 
812 INFECTIOUS DISEASES. 
 
 three hours and forty-three minutes in the injected animals. The 
 differences are appreciable, but not important. 
 
 Clearer results may be obtained by the employment of sulphindi- 
 gotate of sodium. When 2 c.cm. of a 3 per cent, solution of this 
 substance is injected into the veins of a rabbit, at the end of three 
 or four minutes a urine of a decidedly blue color begins to flow. 
 The passage of the coloring substance is, therefore, effected far too 
 rapidly to permit the experimenter to notice differences in hydremic 
 animals. Hence, I simply sought to learn whether, by injecting 
 salt-water after the introduction of indigo, I favored the elimination 
 of this coloring matter. The results were similar to those obtained 
 with ferrocyanide : the urine recovered its normal aspect at the end 
 of four hours and a half in the controls, and at the end of three 
 hours and a half to three hours and fifteen minutes in the treated 
 animals. It is understood that in all these experiments the varying 
 degrees of dilution of the excreted fluid were always taken into 
 account. 
 
 In order to obtain a more convincing demonstration of the influ- 
 ence exercised by injections of salt-water, I introduced into the 
 veins 15 to 20 c.cm. per kilogram of a 3 per cent, solution of sulphin- 
 digotate of soda. The animals soon presented a bluish color, fairly 
 appreciable in the nose, lips, gums, nictitating membrane, and con- 
 junctiva. On cutting off the fur the skin was found to be of a 
 deep blue color. Preserving one animal as control, I injected salt- 
 water into the other. An injection of 130 c.cm. per kilogram 
 notably accelerated the return of the normal color, especially in the 
 mucous membranes. At the end of an hour and a half, for example, 
 the buccal, nasal, and ocular mucous membranes became grayish; 
 at the end of two hours or two hours and a half they recovered 
 their normal hue. At this moment, in the control animals the 
 same parts were still of a slightly greenish-blue. The differences 
 were analogous with regard to the skin, but they were less marked. 
 With the controls as well as with the treated animals, decolorization 
 was effected far more slowly in the skin than in the mucous mem- 
 branes. The results were the same in the viscera. On sacrificing 
 the animals at different moments I noticed that decolorization 
 was more rapidly produced in those which had received salt-water 
 injections. For example, at the end of three hours the liver had 
 resumed its normal aspect, while it was still blue in the controls. 
 The kidneys remained colored for a longer time, but their color 
 
THERAPEUTICS OF INFECTIOUS DISEASES. .-].". 
 
 was less marked. Lastly, a1 the end of seven bom . the .1 nim.-i I- 
 treated presented very little, if any, abnormal color; while the 
 kidneys and the tendons of the controls were still blue. 
 
 [t may, therefore, be concluded thai intravenous injection 
 salt-water truly realize lavage of the Mood or rather of the organism ; 
 they hasten the appearance of ferrocyanide of potassium in the 
 urine and accelerate its elimination. Finally, as our experiment* 
 with indigo demonstrated, they promote elimination of noxious sub- 
 stances deposited in the tissues. 
 
 It would be worth while to take up the study of the question I y 
 varying the doses and employing the mosl varied substances. I< 
 would thus be possible lo establish the laws of elimination. All 
 that we can say a1 present is thai injections of artificial serum seem 
 to produce divers effects according to the substances employed. 
 They favor elimination of some and hinder thai of others. 
 
 Influence of Injections of Artificial Serum upon the Functions 
 and Nutrition of the Organism. The study of strychnine intoxica- 
 tion enabled me to recognize thai injections of artificial serum 
 modified the responsive aptitudes of the organism. In order to 
 avoid errors arising from modifications in absorption, it is necessary 
 to introduce the poison directly into the veins. The results were 
 extremely clear. By injecting into the veins doses of strychnine 
 which produced no disturbance in the controls, I caused fatal con- 
 vulsions in the hydremic animals. In several of my experiments 
 the injections were made very slowly. I thus hoped to allow time 
 for renal elimination to take place; but no matter whether the rate 
 of the injections was rapid or slow, the result was the same. The 
 conclusion is, therefore, that salt-water injections increased reflex 
 excitability; the employment of strychnine was designed to deter- 
 mine the sensibility of the spinal cord. The concordant results 
 obtained demonstrate that saline infusion produces a dynamogeny 
 in the nervous centres. This therapeutic method is. therefore, 
 indicated in all cases of depression or asthenia. Clinical experience 
 shows that this deduction is well founded. 
 
 Another point on which clinical observation and experimentation 
 are agreed is the influence exercised upon the blood pressure. In 
 certain cases pressure rises by a very simple mechanism. For 
 example, in the ease of an individual in whom the arterial pulsation 
 is no longer appreciable, and death seems to be imminent as the 
 result of profuse hemorrhage, injection of salt-water into the veins 
 
814 ISFECTIOUS DISEASES. 
 
 revives the patient immediately; the cardiac pulsations are strength- 
 ened, and the pulse improves. On the other hand, it may be sup- 
 posed that the injections also act upon the nervous centres and 
 that they indirectly raise blood pressure. This action may account 
 tnr the results obtained in the treatment of infections of the digest ive 
 canal, such as cholera, enteritis, and infections of the peritoneum. 
 It is precisely in such cases that the blood pressure falls to the 
 minimum. Bosc and Yedel demonstrated the good results of saline 
 injections in animals which were inoculated with the colon bacillus. 
 On the other hand, Enriquez and Hallion followed the variations 
 of blood pressure in animals at the last stage of diphtheritic intox- 
 ication. Under the influence of the injections the blood pressure, 
 which had been very low, was seen to rise progressively, while the 
 various symptoms improved. Amelioration was not, however, 
 permanent. This was probably due to the fact that experimental 
 intoxication was too brutal, and the animals could not be saved. 
 
 The nervous and circulatory functions as well as all the tissues 
 of the organism are favorably influenced by injections of salt-water. 
 L. Gamier and Lambert demonstrated that the muscles consumed 
 more oxygen and eliminated more carbonic acid. This modification 
 seems to be quite independent of any nervous influence, since it 
 was observed in the muscles separated from the body of the animal. 
 The same authors have likewise discovered that the amount of 
 glycogen diminished in the liver, not because it was eliminated, but 
 simply because the hepatic cells had become more active and con- 
 sumed it more rapidly. Chemical analysis thus agrees with experi- 
 mentation and clinical observation to establish that artificial serum 
 is a powerful stimulant of nutritional activity and that it possesses 
 a high dynamogenic power. Histological investigations prove the 
 same thing. To be convinced of this, it suffices to examine the 
 bone-marrow of animals submitted to this medication. I recognized, 
 with Dr. Josue, that fat was rapidly absorbed and the cells of the 
 marrow proliferated. This fact presents certain interest from the 
 standpoint of pathological physiology, since it is known that bone- 
 marrow, by furnishing round cells to the blood, plays an important 
 role in the defense of the organism against infections. 
 
 Indications of Injections of Artificial Serum. The first attempts 
 were made as early as 1831. Joeniken, of Moscow, injected slightly 
 acidulated water into a cholera patient at the point of death. The 
 patient died two hours later. A Scotch physician, Latta, in 1832, 
 
THERAPEUTICS OF INFECTIOUS DISEASES. -\., 
 
 advocated intravenous injection* of all water in cholera. In 1850 
 Zimmermann treated by thie method a certain numbei of cholera 
 patients, and reported thirty cure Lorain, in 1866, and Dujardin- 
 Beaumetz, in L876, reported other facl . The e fii I attempt* did 
 not, however, have follower , and we musl turn to the contributions 
 oJ Hayem to see intravenous injection or artificial erum take - » r t 
 importanl place in i herapeul ic . 
 
 Subcutaneous or intravenous injections of jail water are al pre 
 employed in the treatmenl of the mosl varied infections. The 
 quality of fluid to be injected has been varied. On the ba 
 highly interesting theoretical considerations, Quinton has recently 
 proposed to employ diluted sea-water. This liquid U .— - » i * 1 to be 
 better borne and to exercise a more energetic therapeutic action. 
 
 In our wards we employ either 8 per 1000 solutions ol aalt-water 
 or Hayem's serum, which, as is known, contains 5 grams of Na< 'I and 
 10 grams of Na 2 S0 4 per litre (quart). Hie liquid i- Bterilized and 
 introduced after being heated to 104° F. C4()° ('.). Dawborn fin- 
 ployed solutions heated to 120.2° V. I I*.) C). While the experi- 
 ments of Riehet, Langlois, and Atlianasiu demonstrated that injec- 
 tions of hot water are well borne by animals, those of Lepine and 
 ours show, on the other hand, that ice-water does not produce any 
 disturbance. It may be concluded that the body heat may be 
 modified by injections of more or less heated fluids. For the time 
 being, it seems more prudent to employ solutions the temperature 
 of which is near that of the body. This precaution is indispensable 
 when an intravenous injection is practised. It is less important in 
 subcutaneous injections. When it is necessary to act promptly, 
 intravenous injection is preferable. If. however, the vein cannot 
 be discovered, for example, in an obese individual or in a patient 
 whose bloodvessels have contracted, intraperitoneal injection may 
 be practised. According to experiments pursued on animals, this 
 method is harmless and has the advantage of permitting very rapid 
 absorption. When there is no urgency the fluid may be in;- 
 into the rectum, after having given an evacuative enema. 
 
 Whatever the route of introduction, injections produce identical 
 effects, appreciable especially in the cast 1 oi intravenous injections. 
 Bosc, Vedel, and Michaux have described the various manifestations 
 observed under these circumstances. During the injection, the 
 pulse becomes slower, more regular and stronger. The central and 
 axillary temperatures slightly rise: sometimes diarrhea is produced. 
 
816 IXFECTIO US DISEASES. 
 
 Immediately after the injection, the patient experiences a feeling 
 of quiet exhilaration which lasts from thirty minutes to an hour. 
 Then violent chills supervene ; the extremities become cold and blue ; 
 the pulse and respiration are accelerated, and the reflexes exagger- 
 ated. The temperature rapidly rises. The patient then experiences 
 a sensation of heat. This second stage is followed by a more or 
 less rapid return to the normal. In certain instances fever dis- 
 appears completely and in a definitive manner. Owing to the violent 
 reaction thus produced, the organism seems to have arrested the 
 morbid evolution. 
 
 After subcutaneous injections similar reactions occur, but they 
 are more tardy and less intense. Intravenous injection is indicated 
 particularly in very acute infections and in diseases aggravated by 
 a sudden complication. Cholera and choleriform diarrheas belong 
 to the first instance; peritoneal infections, supervening in conse- 
 quence of a surgical operation or in the course of an infection, may 
 likewise be treated b}^ this method. In cases of peritonitis, a reduc- 
 tion in arterial pressure is not infrequently the first symptom 
 observed. An intravenous injection raises the blood pressure, and 
 thereby stimulates activity of the glands and assures diuresis. The 
 results of intravenous injections are often, however, of a transitory 
 character. It is then necessary to repeat the injection of the fluid. 
 If one litre is injected, four or five similar injections may be given 
 in twenty-four hours. In one case Lejars introduced seven litres 
 in seven hours. In another instance he injected twenty-six litres 
 in nine days. 
 
 Very satisfactory results may also be obtained by combining 
 subcutaneous and intravenous injections. Owing to their immediate, 
 almost instantaneous, effects the latter palliate the early symptoms. 
 The introduction of salt-water beneath the skin furnishes to the 
 economy a provision of fluid which passes slowly into the blood as 
 the emunctories eliminate the water introduced. In infections with 
 a slow course, in adynamic fevers, and in cases of myocarditis 
 subcutaneous injections are usually employed. Finally, when a 
 profound intoxication of the organism is suspected, blood-letting and 
 transfusion may be combined. Everyone knows of this method 
 proposed by Dr. Barre: 150 to 300 c.cm. of blood are taken from 
 a vein, and from 200 to 1200 c.cm. of salt-water are then injected 
 into the veins or beneath the skin. 
 
 The amount of the fluid injected varies considerably according to 
 
THERAPEUTICS OF INFECTIOUS DISEASES. -17 
 
 the individual under treatment, the di ea e ob erved, and th< 
 pursued. In grave cases, from 600 c.cm. to 1000 c.cm. ol artificial 
 serum are introduced into the veins. In mo I ca e the author 
 employs subcutaneous injections. The amount varies accordii 
 the age of the subjecl and the nature and gravity of the ca e. En 
 children about two years of age, from 10 c.cm. to 20 c.cm. suffice. 
 The author generally injects from 200 c.cm. to 300 ccm. in the 
 of adults. II the case is more seriou . from MX) c.cm. to 500 ccm. 
 may be used. Moreover, in case of need, subcutaneous injections 
 may be repeated several limes a day, and it is surprising to see with 
 what facility patients bear them. 
 
 All sorts of infections may be treated by this method. It is 
 employed in all grave pyrexias, notably in those in which the nervous 
 system is extremely weakened and there is tendency to adynamia 
 and cardiac collapse, a dehydration of the organism expressed by the 
 dryness of the mucous membranes and of the skin, a diminution in 
 the amount of urine, and the occurrence of profuse and multiple 
 hemorrhages. 
 
 The existence of pulmonary, renal, or cardiac complication- i- at 
 times considered a contraindication. Lesions of the lungs, the author 
 thinks, contraindicate intravenous injections, hut they should in no- 
 wise prevent subcutaneous injections. He often prescribes artificial 
 serum for children suffering from bronchopneumonia, provided, how- 
 ever, that small amounts be given two or three times a day. The 
 same rule should be followed in the case of renal or cardiac compli- 
 cations. Experience has demonstrated that intravenous injections 
 are often harmful, and if a lesion of the heart is present, this may 
 cause sudden death. On the contrary, subcutaneous injections are 
 well borne. The method is available not only during the stationary 
 period, but at the end and during convalescence from infections. 
 The author has resorted to it several times when recovery was not 
 clearly established, notably at the end of typhoid fever. An injec- 
 tion of 100 c.cm. often suffices to cause the last symptoms to d> 
 pear. During convalescence from infections, when the patient is not 
 restored to health with gratifying rapidity, recourse may be had to 
 injections of small amounts of saline solutions, following the advice 
 of Landouzy. From 10 c.cm. to 20 c.cm. of artificial serum are 
 introduced beneath the skin twice a week. This is a method which 
 renders most appreciable service in the case of tedious convales- 
 cence. 
 
818 IXFECTIOUS DISEASES. 
 
 Special Indications for Injections of Artificial Serum. After the gen- 
 eral study which we have presented concerning saline injections, we 
 shall be very brief on particular indications. 
 
 Numerous cases of surgical, obstetrical, and medical septicemias 
 have been successfully treated by this method. Intravenous injec- 
 tions have mostly been employed. Turner reported two cases of 
 tetanus cured by saline injections preceded by blood-letting. The 
 attempts made 1 in hydrophobia by Magendie, Ore, and Reclus were 
 negative. Among medical affections, digestive infections particu- 
 larly are best treated by this method. Cholera is the disease which 
 is most frequently treated by intravenous injections. In order to 
 succeed, it is necessary, as has been shown by Hayem, to intervene 
 early, as soon as the pulse shows weakness, and not, as is often done, 
 in the period of collapse. From 1500 c.cm. to 2000 c.cm. and even 
 2500 c.cm. are injected into the veins. If the symptoms return, the 
 injection is repeated on the following day. In certain instances 
 recovery has been obtained only after five or six intravenous injec- 
 tions. As has already been stated, there is advantage in injecting 
 at the same time 400 c.cm. to 500 c.cm. beneath the skin. In mild 
 cases the subcutaneous method exclusively is used. Finally, excel- 
 lent results are obtained b}^ prescribing coincidently warm baths so 
 as to maintain the temperature of the body and avoid return of the 
 algid state. The same rules are applicable to choleriform ententes. 
 The indications are the same; the less grave the symptoms the more 
 sufficient the hypodermic method generally proves to be. Treatment 
 is likewise identical in cases of gastroenterites of the newborn and 
 cholera infantum. Marfan advises, with good reason, the addition 
 of a small amount of caff ein to the fluid : 75 eg. of citrate or benzoate 
 of caffein are added to 300 c.cm. of salt-water, and three injections 
 of 5 c.cm. to 20 c.cm. daily are given. 
 
 Typhoid fever, especially its adynamic forms, is favorably influ- 
 enced by the injections. In the case of intestinal hemorrhage, the 
 effects of the injections are very remarkable. In order to be con- 
 vinced of this, it suffices to bleed an animal. At the moment at 
 which death seems to be imminent an intravenous injection is prac- 
 tised, and immediately the heart beats with energy and all the dis- 
 turbances disappear. In mild cases saline injection beneath the skin, 
 and, if the symptoms are alarming, into the veins, is the preferable 
 treatment. By this method patients who had already fallen into a 
 state of collapse have been cured. The second important complica- 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 819 
 
 tion i. c, perforation of the inte tine lik< ri e require b saline 
 injection, which renews the forces of the patienl and enables him to 
 bear surgical intervenl ion. 
 
 Among other infection . typhus fever, typhoidal affections . notably 
 ulcerating endocarditis and adynamic pneumonia, musl ix 
 by subcutaneous injections. The author employs them also in erup- 
 tive fevers, at leasl in grave forms, and in erysipelas. When the 
 manifestations persisl and the temperature remains high in Bpite of 
 cold baths, subcutaneous injection often i unices to bring aboul 
 defervescence. In several cases, after having introduced 300 c.cm. 
 to 100 c.cm. beneath the skin, the symptoms disappeared within 
 twenty-four hours. This method may be employed even u 
 wandering erysipelas. Ii is then accessary to inject the fluid into 
 a part of the organism far from the diseased spot. 
 
 To sum up, barring a few particular cases, which we have indicated 
 above, saline injections represent one of the best methods of treat- 
 ment of infectious diseases. They succeed far better in man than 
 in animals, probably for the reason that the nervous system in man 
 is far more profoundly affected. By stimulating its activity, the 
 injection favors general nutrition and the functions of the principal 
 organs. Moreover, it perhaps acts also by furnishing water to the 
 organism. We have several times referred to the importance of water 
 for the activity of the cells, and if it is true that in the fight against 
 infections, the organism tends to return to a functional state char- 
 acteristic of a younger age, the chemical formula of this tendency is 
 an increased amount of water. This is a new reason, based upon 
 numerous analyses, for having recourse to injections of salt-water. 
 
 Symptomatic Medication. 
 
 In a great number of cases the physician must combat certain 
 symptoms or complications regardless of the mechanism governing 
 their development. It is then a question of dangerous or painful 
 disorders, which are about the same in all infections, and require a 
 common therapeutics. Among these disorders several have already 
 been studied, and we shall only briefly recall their indication. Of 
 others we shall speak at some length. 
 
 Treatment of Febrile Manifestations. "We have sufficiently indi- 
 cated the rules that must guide us in the treatment of fever and have 
 shown that the only rational medication is represented by cold or 
 lukewarm baths. In cases in which fever starts with chills and in 
 
820 INFECTIO US DISEASES. 
 
 those iii whom chills occur in the course of a pyretic infection, the 
 patient must be mechanically heated. As has already been stated, 
 chills represent a reaction of the organism calculated to raise the 
 temperature in order to combat the hypothermizing action of toxins. 
 At this, moment the skin is cold and pale, owing to contraction of 
 the small peripheral arteries. Since the investigations of Marey it 
 is known that when the skin is cold it means that the individual 
 tends to become heated, and that when the skin is warm he tends 
 to become cold. This formula, paradoxical in appearance, is, never- 
 theless, very simple. When the skin is cold, dissipation of heat is 
 reduced as much as possible; this dissipation increases as the cuta- 
 neous temperature rises. When, therefore, the skin of an individual 
 is cold, heat must be furnished, and when the skin is warm heat must 
 be abstracted. In both instances naturalistic medication is prac- 
 tised. Consequently, during chills the patient must be well covered, 
 and hot water bottles should be placed in his bed. Moreover, to the 
 same end, hot beverages must be given. This medication is a popular 
 one. Mistaking the effect for the cause, many persons think that 
 the initial chills, notably in influenza, represent a cold which causes 
 the disease, and flatter themselves as to their ability to arrest the 
 evolution by means of hot applications and beverages. The effect 
 is real, but the interpretation is erroneous. The truth is that it is 
 not the chill that is combated, but the organism is assisted in warm- 
 ing itself. 
 
 At the end and at times during the course of fevers, sweating is 
 not rare. It commonly appears at the end of a paroxysm after the 
 period of heat. Sweating requires some hygienic precautions. The 
 perspiration should not be allowed to grow cold upon the skin. The 
 becl-clothes should, therefore, be changed, dry friction practised, and 
 the patient covered with blankets. Finally, as sweating gives rise 
 to thirst, the patient must be given drink; hot beverages and infu- 
 sions should be administered. The sweating of cachectic and tuber- 
 cular patients requires special treatment. Five milligrams of agaricin 
 and two to five grams of camphoric acid may be prescribed. The 
 best medicine, however, is, without doubt, the neutral sulphate of 
 atropin. One-half milligram granules are first given, and if this dose 
 proves to be insufficient, two, three, and even four of them may be 
 administered in a day. Sweating must be combated, particularly 
 during the night, as, by its abundance, it disturbs the sleep of the 
 patients. The author has sometimes observed night-sweats during 
 
TSEBAPEUTIOS OF INFECTIOUS DI8EA8E8. 821 
 
 convalescence from acute infection , A granule of atropin given 
 three or four evenings in succession suffice* to make them disappear. 
 
 In infections which terminate by cri i . notably in pneumonia, the 
 temperature may suddenly fall below the normal. This disturbance 
 is transitory in adults, bu1 in children, and <■ pecially in the aged, 
 hypothermia may be excessive and at tended by alarming phenomena 
 of collapse. Hot baths, hot water bottles, cutaneom friction, and 
 stimulating medicines musl then be prescribed. 
 
 Treatment of Nervous Manifestations. The general treatment of 
 nervous disturbances, whether the case i one of excessive excitation 
 or depression, consists in lukewarm or cold baths. 'Hi- if the best 
 procedure for regulating the nervous functions, remedying delirium, 
 and inducing sleep. It is likewise the treatment for thai frequent 
 and alarming symptom observed in children — i. e., convulsions. 
 These are not rare at the beginning of infections. ConvulsioM are 
 the equivalent of chills in adults. Commonly transitory, they require 
 no special treatment. A few hygienic rules suffice. Mosl parents, 
 frightened at seeing their children suffering from convulsions, have 
 the deplorable habit of taking them in their arms, slapping them 
 on the back, and walking the floor with them. On the contrary, they 
 should be kept at rest. The child should be placed in a large bed 
 so as to avoid the danger of falling out when agitated. The room 
 should be kept in semidarkness and free from noise. When convul- 
 sions are repeated the}' indicate a lesion in the nervous centres or a 
 too great excitability of the child. In the latter case they are the 
 equivalent of delirium. It is then necessary to resort to lukewarm 
 baths at 100.5° F. (38° C.) during the intervals of convulsion, or, if 
 fever is intense, to baths gradually rendered cold so as to reach 
 a temperature of S9.5° or even 86° F. (32° or 30° C). For the 
 same purpose antispasmodic preparations may be employed, among 
 which the most usual are the tinctures of musk, asafetida, and vale- 
 rian, which are prescribed in doses of ten to thirty drops, according 
 to the age of the children. In the case of gastric intolerance, a musk 
 enema is generally given. 
 
 The treatment of delirium requires special consideration. Balneo- 
 therapy takes the first rank. In young and robust adults cold baths 
 are given. In children and persons above forty years of age. luke- 
 warm baths are administered. It is well to note, however, that in 
 these cases cold effusions should be practised upon the head during 
 the bathing. If the patient is much agitated, for instance, in the 
 
822 INFECTIOUS DISEASES. 
 
 case of alcoholic delirium, an additional difficulty faces us. After 
 having been brought back to his bed, the patient may attempt to 
 get out and, even when constantly watched, he may at times succeed 
 in rising. It is then necessary to force him to lie down again. In 
 hospitals the difficulties are still greater, and physicians are some- 
 times compelled to resort to coercive measures. One of the best 
 methods, which, however, is applicable only to mild cases, consists 
 in placing on each side of the bed a plank so as to prevent an easy 
 escape. When delirium is more intense it is necessary to bind the 
 patient, but in such a maimer as to allow him to move easily in the 
 bed. 
 
 The therapeutic indications vary according to the cases under 
 treatment. There is a neuropathic delirium related to a previous state 
 of the individual, and there is a delirium dependent upon chronic 
 intoxications, notably alcoholism. Neuropathic delirium, when not 
 very intense, requires no special therapeutics. Balneotherapy is 
 sufficient. When intense, delirium must be treated by means of anti- 
 spasmodics. Bromides may render service. In infectious diseases, 
 which are so often attended by cardiac or renal disturbances, it is 
 well, in general, to avoid potassium salts. Bromide of sodium should 
 be given in doses of from two to four grams a day. Musk is also 
 available, but the medicine to which the author resorts most fre- 
 quently is valerian. The best preparation is the extract, of which 
 4 to 6 grams are given a day. An infusion of the root is also useful, 
 15 to 30 grams of which may be given as an enema, or a 10: 1000 
 infusion of half an hour. Valerian acts mostly by the isomeric carbo- 
 hydrate of turpentine oil, which it contains, and not by valerianic 
 acid. The author, therefore, avoids the use of valerianate of am- 
 monia. 
 
 In alcoholic delirium occurring in the course of an infectious dis- 
 ease, the extract of valerian may be employed. The true medication, 
 however, is alcohol associated or not with opium. In our hospitals 
 Todd's potion is usually prescribed. The French Codex formulates 
 it in the following manner: old brandy or rum, 40 grams; simple 
 syrup, 30 grams; tincture of cinnamon, 5 grams; distilled water, 
 75 grams. 
 
 As brandv and rum contain 45 to 60 per cent, of alcohol, the 
 amount given above is too small. In fact, Todd prescribed from 
 100 grams to 150 grams of brandy in twenty-four hours for cases of 
 medium severity, and from 300 to 500 grams in grave cases. The 
 
THERAPEUTICS OF INFECTIOUS DISEASES. W, 
 
 second Indication, however, formulated by Todd, and which u per 
 haps the most important but is often overlooked, i thai the alcoholic 
 potion is not to be given in very large do e . According to 'In- 
 famous clinician, II grams of brandy should be given ev< 
 hours. If this precept is no! followed, grave accidents may I"- pro 
 duced by the use of this alcoholic beverage. A very simple procedure 
 consists in giving a dessertspoonful of rum with two or three timet 
 its volume of sweetened water every two hours. If the agitation i- 
 extremely violent, alcohol may be associated with opium. This ■ 
 ciation is frequently in< lic-i I «•< I in pneumonia, erysipelas, and variola. 
 From 5 eg. to 10 eg. of extracl of opium or from 20 to 1 ( ) drops of 
 Sydenham's laudanum is given in twenty-four hours. The opium 
 preparations are likewise to be given in fractional doses. The desired 
 quantity may be given in Todd's potion or with wine. Wine to 
 which the daily dose of laudanum is added has s very remarkable 
 action; one litre of such wine may be given in twenty-four hours. 
 If there is tendency toward adynamia, champagne is to he preferred. 
 The treatment must be completed by certain medicines calculated 
 to combat cardiac disorders which are so frequent in such a 
 Spartein and strychnine may be administered subcutaneously. One 
 cubic centimetre of a solution containing 5 eg. of sulphate of spartein 
 and 1 mg. of sulphate of strychnine may be injected morning and 
 evening. 
 
 This treatment would be perfect if the cerebral disorders of alco- 
 holic patients did not frequently coexist with renal lesions. Albu- 
 minuria absolutely contraindicates the employment of alcohol and 
 of opium, which then produce extremely grave phenomena of 
 depression. Baths, bromides, and valerian will suffice in such a - - 
 Moreover, let us recall that, in certain cases, delirium may be cured 
 by specific medication. Quinine should be given in the case of 
 malarial delirium and mercury and iodides to syphilitica. 
 
 When the nervous system is much excited insomnia is frequent. 
 This disturbance is combated by the medications directed against 
 delirium and by the general therapeutics of infection. If. notwith- 
 standing the baths, insomnia should persist, hypnotics must be 
 employed. As the patients soon become accustomed to their action, 
 it is well to change the medicine as soon as its effect is exhausted. 
 One gram of sulphonal, of trional, or of hypnal, 2 grams of chloral 
 hydrate, or a mixture of chloral and bromide of sodium, in the dose 
 of 1 gram of each, may be administered. Opium should be mis- 
 
8 2 4 IXFECTIO US DJSEA SES. 
 
 trusted. It is indicated only in alcoholic patients and in the course 
 of variola. Even in these cases, however, it is to be avoided if there 
 is albumin in the urine or the secretion is too scanty. In children 
 lukewarm baths almost always suffice. In case of need a little 
 bromide of sodium or calcium may also be prescribed; 20 eg. or 
 25 eg. for each year of the age may be administered. 
 
 ^'hen the nervous system seems to be exhausted, diffusible stimu- 
 lants are to be resorted to. Potions containing rum or brandy, cham- 
 pagne, and vinous beverages may be prescribed. Wine may be given 
 to children; 30 to 60 grams of Malaga would be an excellent dose. 
 The wine of Bagnols is used in the cordial potion of the French 
 Codex: 110 grams of Bagnols, 40 grams of syrup of bitter orange- 
 peel, 10 grams of tincture of cinnamon. Coffee and preparations of 
 caff em may likewise be employed. 
 
 Among stimulants, ether may be utilized. Thirty grams of syrup 
 of ether is given in a julep to which four grams of acetate of ammonia 
 are added. Ether may likewise be administered subcutaneously. The 
 injections must be made quite deep into the tissues; otherwise they 
 are very painful, and, what is graver, at times give rise to small 
 eschars. One or two cubic centimetres of pure ether is generally 
 injected, and may be repeated every hour. Du Castel has emphasized 
 the satisfactory effects obtained in variola by the combined treat- 
 ment of ether and opium. One cubic centimetre of ether is injected 
 morning and evening, and from 6 eg. to 10 eg. of extract of opium 
 are at the same time prescribed, according to the severity of the 
 delirium. 
 
 The injections of ether may with advantage be replaced by those 
 of camphorated oil. A 1: 3 solution is employed; in some cases one- 
 tenth of ether is added to it. Camphor exercises a powerful dyna- 
 mogenic action upon the nervous system. It may be administered 
 in the form of enema ; in this case it is suspended in a gum arabic 
 emulsion containing in 250 grams of the fluid, 1 gram of camphor, 
 
 2 grams of gum arabic, and the yolk of one egg. 
 
 Among the nervous disturbances of convalescents we may cite 
 various paralyses which may be treated by two procedures : an inter- 
 nal treatment represented by strychnine, given in doses of 2 mg. or 
 
 3 mg. of the sulphate or the arsenate; an external treatment repre- 
 sented by electric currents. If there is albuminuria at the same 
 time, electricity alone is to be employed. Faradic currents are 
 generally used. 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 
 
 Treatment of Cardiovascular Manifestations. I [carl disturbance* 
 are so frequent and importanl in various infection thai the: 
 particular attention and often require special treatment. 
 
 The physician has seldom to combal erethism. [1 ometimes 
 ()( . ( .,ii- s in the beginning of pericarditis. The therapeutic indications 
 consist mainly in revulsive measures: dry or we\ cupping over the 
 precordial region and thermocauterization may daily be applied. 
 Coincidently, bromide of sodium or, whal seen,, to be preferable, a 
 mixture of 2 grams of the bromide and I gram of iodide of sodium 
 may be prescribed. The vasodilatation produced by the latter medi- 
 cine diminishes cardiac erethism and the painful phenomena accom- 
 panying it. II' Hie latter arc very marked, opium preparations, auch 
 as Dover's powder or injections of morphine, may al the same time 
 be prescribed. In most cases the period of excitation is transitory 
 and too often yields to a state of depression depended upon myo- 
 carditis. 
 
 Whatever may be its cause, myocarditis has importanl therapeu- 
 tic indications. The first question arising is: Should the cold baths 
 be continued? It is true that patients who receive baths are less 
 frequently liable to develop myocarditis. When, however, it is devel- 
 oped the baths should be suspended. In fact, the first indication con- 
 sists in the avoidance of all movement and all displacement of the 
 patient. Coincidently, alcohol or coffee are to be prescribed; injec- 
 tions of ether, of camphorated oil, and, above all. subcutaneous 
 injections of artificial serum, must be practised, the latter, however, 
 in' small amounts often repeated. Among cardiac medicines, digi- 
 talis is, in this connection, the least effectual; 5 eg. of sulphate of 
 spartein, tincture of strophantus, or strophanthin, and especially 
 caffein, are to be employed. If the symptoms are not too serious, 
 caffein, given in a potion, will suffice. It is dissolved by benzoate 
 of soda, the influence of which upon oxidations is appreciable. In 
 this case the author prescribes a stimulating potion formulated as 
 follows: rum, 30 grams: syrup of bitter orange-peel, 30 grams: Hoff- 
 man's anodyne, 1 4 grams: tincture of cinnamon, 2 grams: benzoate 
 of soda, 4 grams: caffein, 1 gram: linden flower water, 60 grams. 
 One tablespoonful every half hour is taken. 
 
 In case of urgency, subcutaneous injections must be practised. 
 The classical solution is then employed: benzoate of soda. 3 grams: 
 
 » The French preparation of Hoffman's anodyne consists of equal parts of ether and 
 
 alcohol. 90°.— Translator. 
 
826 INFECTIOUS DISEASES. 
 
 caffein, 2.5 grams; distilled water, sufficient quantity to make 
 10 com. Each Pravaz syringeful contains 25 centigrams of caffein; 
 three or four injections may be given in twenty-four hours. When 
 the phenomena of collapse appear, injections of caffein are to be 
 alternated with those of ether, or camphorated oil, or sulphate of 
 strj^chnine, of which 1 milligram is injected twice a day. Lastly, 
 when arterial pressure is very low — Potain has seen it fall to 13 or 
 even 6 cm. — a little ergotin ma)*- be given. In case of fainting, the 
 habitual means are employed: horizontal decubitus, the head a 
 little low, flagellation, artificial respiration, and rhythmic traction 
 of the tongue. 
 
 If the patient recovers, he is to be kept on milk diet for a long 
 time, and the avoidance of movements and displacements must 
 be emphasized. Finally, some cardiac medicine must be prescribed, 
 among which I prefer strophanthus (1 to 2 milligrams of the extract 
 or ten to fifteen drops of the tincture) . The hypertrophy consecutive 
 to infections requires no special treatment. The treatment of 
 chronic cardiopathies is to be applied — i. e., hygienic precautions 
 and avoidance of fatigue. As to pharmaceutical measures, long- 
 continued medication with iodide and bromide yields the most 
 satisfactory results. 
 
 For twenty days each month a daily dose of 1 gram of bromide 
 of sodium and 80 eg. of iodide of sodium, with 20 eg. of iodide of 
 potassium, should be given. 
 
 Endocarditis is less frequent and requires no special therapeutics. 
 At the beginning, treatment is the same as in pericarditis. In case 
 of need, cardiac erethism must be quieted by means of revulsives. 
 If the heart muscle shows signs of failure, the same treatment as 
 for myocarditis may then be prescribed. 
 
 Vascular and notably arterial complications are very rare. Should 
 the aorta be affected, the treatment must consist in revulsive 
 measures. In the case of peripheral arteritis, the first indication is 
 to place the affected limb in a good position and surround it with 
 hot compresses. When ischemia terminates in sphacelation, sub- 
 cutaneous injections of antiseptic substances must be resorted to. 
 The author employs neutralized peroxide of hydrogen. Bouchard 
 obtained success by interstitial injections of creosote. Formol and 
 camphorated salol have likewise been employed for the same pur- 
 pose. If the gangrene extends or the general state is aggravated, 
 amputation must be practised. 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 827 
 
 Treatment of Respiratory Manifestations. Respirator) di 01 
 require very active therapeutics, [n the firsl place the nasal foci 
 may ho the seat of a serous, mucous, or purulenl catarrh. 
 
 Iii some cases the inflammation extends to the inn e of the face. 
 In tho caso of a simple serous catarrh, a slightly antiseptic powder 
 is snuffed or a little menthol is inhaled. In the case of purulent 
 coryza 1-1 10 host treatment consists in menthol inhalations. The 
 vapor penetrates into the interiorof the nose and even the -n 
 and realizes a certain degree of antisepsis. A tablespoonful of a 
 3 per cent, alcoholic solution of menthol is pul in a howl of hot water* 
 which is then covered with a funnel turned down, and the patienl 
 is instructed to breathe the vapors rising through the tube of the 
 funnel. In more serious cases, lavage must be resorted to accord- 
 ing to the procedures which wo have already indicated. Then a 
 salve with resorcin and menthol must be introduced. The em- 
 ployment, of menthol in the form of inhalations and of salves is 
 the best treatment to oppose the development of sinusites. Lastly, 
 it is well to remember that the discharges from the nose often 
 irritate the upper lip; hence the epidermis must be protected by 
 means of a salve, such as vaselin containing boric acid or bismuth. 
 When lesions involve the larynx, menthol inhalations may likewise 
 be employed. The medicinal vapor thus reaches the entire upper 
 part of the respiratory tract. It is advisable, at the same time, to 
 keep the patient in a rather humid atmosphere. For this purpose 
 slightly antiseptic fluids, such as earbolized-water or benzoin-water, 
 may be sprayed about the patient. If the lesions are more profound . 
 notably, if they terminate in the production of ulcerations, stronger 
 medication is necessary. Spraying should be done with Van Swieten's 
 solution,or with naphtholated water. The latter medicine is em] »1< ryo 1 
 as follows: 25 eg. of naphthol in 25 c.cm. of alcohol and 75 c.cm. of 
 water. In rare cases it may be necessary to touch the larynx directly 
 by certain local medicines. Some medicines administered by the 
 mouth may exercise a favorable action upon the larynx: some of 
 them stimulate the secretions, others dimmish the spasmodic 
 element which is superadded to the inflammatory process. Nitrate 
 of pilocarpin is very serviceable in the former case. I inject sub- 
 cutaneously, at two different times, \ c.cm. of a 1 per cent, solution. 
 The spasmodic element must be combated by belladonna frequently 
 associated with aconite. A mixture of equal parts of tincture of 
 belladonna and aconite root is used, thirty drops a day in three 
 
828 INFECTIO US DISEASES. 
 
 doses. Bromides, bromoform, and codein may also be used for the 
 same purpose. 
 
 We should like to call special attention to the frequency of ex- 
 tremely troublesome night coughing in certain infections and par- 
 ticularly certain epidemics of influenza. These coughing spells 
 sometimes last an hour or more and give rise to great fatigue. The 
 true treatment consists in giving, at the moment of the spell, one or 
 two tablespoonfuls of the following potion in a little water: bromo- 
 form, 1 gram ; syrup of codein, 40 grams ; cherry-laurel water, 5 grams ; 
 white looch, 80 grams. 
 
 Applications upon the cervical region are quite frequently prac- 
 tised. They may be employed cold or hot. In the former case 
 the intention is to exercise an antiphlogistic action. Hot applications, 
 however, are being more and more resorted to, as they are anti- 
 spasmodic, and at the same time stimulate reactions. Laryngeal 
 spasm, notably in young children, may very rapidly be soothed by 
 means of hot applications upon the neck, and at the same time by 
 inhalation of steam. When, in spite of all these medications, the 
 disturbances persist, when the spasm becomes too intense or lasts 
 too long, or when an obstacle to the entrance of air results from deep 
 lesions, pseudomembranes, edema, or ulcerations, the passage of air 
 should be re-established by tracheotomy. 
 
 As is known, bronchitis is extremely frequent in the course of the 
 most varied infections. When slight, it needs no particular treat- 
 ment. When intense, bronchitis does not contraindicate balneo- 
 therapy. On the contrary, the baths should be continued, even 
 cold baths; under their influence vascular constriction is produced, 
 which reduces the congestive phenomena. If the individual is too 
 nervous, or if too violent excitation is feared for some reason or 
 other, warm baths at 96.8° or even 100.4° F. (36° or 38° C.) may be 
 given every three hours. This treatment is also indicated when the 
 inflammation extends to the small bronchi and terminates in broncho- 
 pneumonia. At the same time applications to the chest may be 
 employed. They are useful in all complications of the respiratory 
 apparatus. The heating compress gives excellent results. A piece 
 of muslin is folded eight or ten times and immersed in water at 
 59° or even 50° F. (15° or 10° C). It is then wrung out and applied 
 upon the chest of the patient and covered with oiled silk. At the 
 end of two or three hours the compress is removed. The chest is 
 then found very hot and the skin red and congested, as if a sinapism 
 
THERAPEUTICS OF INFECTIOUS DISEASES. 
 
 had been applied. The treatment acts by the revulsion and the 
 aervous excitation which H induces, which resull in deeper respira- 
 tion and at times in :i spell of coughing which expel muco itii 
 
 Cutaneous revulsion may also be practiced by meant of 
 poultices sprinkled with mustard Hour, and dry and wel cupping, 
 [f the lesions are circumscribed, tincture of iodin may be used to 
 which a little guaiacol is added in the proportion of 2: LO or 5: I". 
 or a salve with guaiacol in the proportion of I \ ; 10 or 1 : 10. It i- 
 better (,<> abstain from vesica tones which, in an organism already 
 infected, may aggravate the urinary disturbances and even cause 
 cutaneous lesions, and thus open a route for secondary infection. 
 Finally, in children, a more extensive revulsive action may be 
 exercised by prescribing lukewarm mustard baths: 150 or 200 grama 
 of mustard (lour is put in a linen bag, which is first plunged into cold 
 water, then into the water of the bath. In very young children 
 revulsion is obtained by means of hot friction. Camphorated 
 chamomile oil is put in a cup and heated over the flame of a candle, 
 and then hot friction is practised with the hand upon the abdomen 
 and lower extremities, which are then covered with a thick layer 
 of cotton. As to the degree of temperature at which the oil is to 
 be used, it is not necessary to determine it accurately. The parents 
 should be instructed to employ it as hot as the hand can bear. 
 
 These various procedures are designed to produce revulsion. 
 They sometimes succeed in palliating certain disorders. There is 
 one disturbance, however, which gives much trouble to patients 
 and against which some remedy is always asked: We refer to cough- 
 ing. Let us remark immediately that coughing, although very 
 troublesome, is nevertheless useful at least in certain instances. We 
 must distinguish two kinds of cough: one is dry and spasmodic, the 
 other favors expectoration. The former may be combated, the 
 latter must be respected, for it is intended to eliminate bronchial 
 secretions or exudates of the bronchi and lungs. Various soothing 
 medicines may be prescribed against dry cough: antispasmodics 
 especially opium preparations are useful. Nearly all cough syrups 
 contain opium. The following are very often prescribed: Di:. 
 syrup, which contains 1 eg. of extract of opium to 20 grams of syrup; 
 syrup of morphine, containing 1 eg. of this alkaloid to 20 grams of 
 syrup: syrup of codein, 20 grams of which represent 4 eg. oi codein; 
 the opiated syrup of lactucarium of the French Coder, which contains 
 5 mg. of extract of opium and 1 eg. of extract of lactucarium in 
 
830 INFECTIOUS DISEASES. 
 
 20 grams of syrup. These various syrups are often mixed with 
 syrup of belladonna and cherry-laurel water. 
 
 Even when coughing serves expectoration, it may be combated 
 by the various therapeutic procedures above indicated. For, 
 although it is useful, it sometimes is so troublesome as to disturb 
 the rest of the patient and, therefore, must be moderated. In this 
 case, however, it is advisable to abstain from opium preparations 
 and resort to expectorants. Emetics are at times prescribed for 
 this purpose. This medication, which renders appreciable service, 
 is generally well borne by children. The child being incapable of 
 expectorating, the spasmodic shaking of the cough exercises a sort 
 of massage of the lung, and thus serves for expectoration of the 
 exudates encumbering the respiratory passages. Ipecac, however, 
 which is the only emetic available, should not be administered except 
 when infection is of moderate severity and the child vigorous; 
 otherwise it may cause depression and collapse. On the other hand, 
 an emetic is seldom indicated in adults, and should never be pre- 
 scribed for those above forty years of age. If bronchial secretions 
 are profuse or the congestive phenomena intense, ipecac is employed 
 in fractional closes. For this purpose Dover's powder may also be 
 employed. The preparations of antimony are likewise regarded as 
 expectorants. Ammonium salts are also useful in this connection. 
 The Germans frequently prescribe hydrochlorate of ammonia. In 
 France the acetate of ammonia is mostly used in doses of from 
 2 to 4 grams daily. It is usually associated with 20 or 30 grams 
 of syrup of ether. In cases in which the urine is very albuminous, 
 we prefer benzoate of soda in daily doses of from 2 to 6 grams. If 
 after the fall of fever the thoracic manifestations persist, balsamic 
 preparations may be resorted to and, if the process passes to a 
 chronic state, sulphurous medicines may be employed. Among 
 balsamics the balsams of Tolu and terpin are most frequently 
 employed. 
 
 These general rules must be supplemented by a few special indi- 
 cations. When there is tendency toward passive congestion the 
 patient must be instructed to lie down in a certain manner. If 
 possible, he should sit in an arm chair or in his bed. He must at 
 least avoid keeping the same position. He should lie down on one 
 side, sometimes on the left, sometimes on the right. The blood 
 circulation is to be modified by means of revulsives and repeated 
 cupping. Certain medicines may likewise serve to regulate the 
 
THERAPEUTICS OF INFECTIOUS diseases. .-.;\ 
 
 circulation. Some of them acl directly upon the pulmonary blood- 
 vessels, others exerl an indirect action through the heart. Among 
 the former, ergotin may especially be mentioned; among the latter 
 digitalis, cafTein, and strophanthus. Moreover, if a phyxia oc< 
 inhalation of oxygen Is useful, and in ca e of need, scarified cupping 
 or a genera] blood-letting may be pracl ised if the patienl 
 subject. 
 
 When putrid fermentations are produced in the bronchial exudi 
 recourse is to he had to substances which, being eliminated by the 
 respiratory passages, may exert an antiseptic action thereon. For 
 this purpose tincture of eucalyptus is generally given in doa 
 2 grams, and subcutaneous injections of eucalyptol: 5 to 10 c.cm. 
 of a solution in oil (in the proportion of 2 or '■'> per cent .) are injected. 
 Finally, hyposulphite of soda also exercises an appreciable action 
 upon the bronchial secretions: from 4 to 6 grams of it are given 
 daily. All these medications produce no well-marked effect upon 
 the putrefactions of the respiratory apparatus. They seem, however. 
 to act more effectually than inhalations of medicinal substances, 
 such as turpentine and eucalyptus. When a well-localized focus is 
 found in the lung, one is always irresistibly tempted to apply to it 
 some local medicine. Attempts have been numerous, but without 
 encouraging results. Intrapulmonary injections expose to consider- 
 able dangers; hence, they have been almost entirely abandoned. 
 The best intervention is evidently incision and drainage of the 
 morbid focus, provided, of course, that the lesion is circumscribed. 
 There is, however, no chance of success except in the case of indi- 
 viduals primarily affected, viz., in those who are sufficiently robust. 
 Even then the operation is always more or less unsafe, especially 
 in view of the danger from secondary hemorrhages, which are of 
 frequent occurrence. 
 
 Treatment of Disorders of the Digestive Apparatus. Digestive 
 disturbances often hinder the therapeutics of infectious disi - - 
 Vomiting is observed at the start of a great number of infections. 
 They seem to be dependent upon some disorder of innervation. In 
 the majority of cases the manifestation is transitory and requires 
 no treatment. Should vomiting fatigue the patient too much or 
 last too long, it may be allayed by cold applications upon the 
 epigastric region: an ice-bag is placed or ether is sprayed upon the 
 region. At the same time the patient may be given cold and slightly 
 acidulated beverages to drink: or a small quantity of champagne 
 
832 IXFECTIO US DISEASES. 
 
 with a little Seltzer water may be given. If more active intervention 
 is necessary, the classical potion of Riviere 1 is prescribed. The 
 nature of such vomitings being known, however, we prefer medicines 
 which soothe the reflex sensitiveness of the stomach : chloroform- 
 water and belladonna seem to me indicated. We prescribe a mixture 
 of 100 grams of saturated chloroform-water ; 20 grams of syrup of 
 belladonna, and 5 grams of cherry laurel-water, 1 tablespoonful to 
 be taken every hour or half hour. During the stationary period 
 vomiting depends either upon defective secretion or a gastric local- 
 ization, or else upon some complication. 
 
 "We often see patients who, under normal conditions, take milk 
 with pleasure and digest it well, while in the course of infections 
 they can no longer bear it; they vomit it in the form of large curds 
 shortly after they have taken it. In this case milk may be mixed 
 with some alkali, such as Vichy, Vals water, and, especially when 
 there is diarrhea, lime-water. Should this prove insufficient, the 
 digestion must be assisted by pancreatin. This may be given in 
 the form of pills after each cup of milk, or 20 to 30 eg. of it may 
 be added to the milk at the time of administration. Another method 
 consists in giving a small amount of beer yeast, which facilitates 
 considerably the digestion of milk. 2 
 
 It should not be overlooked that vomiting is often due to medicines 
 prescribed. Hence, in many cases, discontinuance of a potion suffices 
 to re-establish the digestive functions. In this regard alcohol and 
 cinchona, which are so often abused, have an unfavorable influence 
 which should be remembered. When vomiting results from gastric 
 localization, more active therapeutics must be employed. If the 
 question is one of simple catarrh, lavage of the stomach will render 
 service. If it is due to ulcer, for example, it is expressed by vomiting 
 of sanguinolent matters, and the stomach must be given absolute 
 rest. No nourishment or beverages should be given by the mouth; 
 nutritive enemas and hypodermic injections of salt-water must be 
 given. Ice is to be applied upon the h}^pogastric region, and opium 
 given either in the form of pills of extract of opium, of which 1 eg. 
 may be administered every hour, or in the form of subcutaneous 
 injections of morphine. The latter method has the advantage of 
 
 1 "Potion de Riviere" has the following composition : potassium bicarbonate, 4 grams; 
 simple syrup, 30 grams; water, 100 grams. — Translator. 
 
 2 Matzoon or zoolak is very often used in America as a substitute for milk when the 
 latter is not well borne. — Translator. 
 
THERAPEUTICS OF INFECTIOUS DI8EA8E8. 
 
 acting more promptly. Moreover, hemorrhage! ma) I" am ted by 
 making a sort of gasl ric dressing by means of subnitrate oi bismuth; 
 u large dose of the latter should be prescribed ; 15 and <■: en M I 
 would Dot be too much. Vomiting due to complications requires 
 no special therapeutics. Ii is dependenl upon nephritis, meningiti . 
 perforation of the intestine, and sometimes to inflammation of the 
 diaphragmatic pleura. If, however, it becomes alarming, the vomit- 
 ing may be combated by the various methods already referred to. 
 and which are to be modified according to circumstance I 
 instance, opium may be given in case of peritonitis, while this drug 
 is to be avoided when there is uremia. 
 
 Finally, at the moment of convalescence, persistenl vomiting 
 formerly observed when the patient was firsl given nourishment. 
 At present, however, the method of absolute did having been 
 abandoned, nothing of the kind is any longer encountered. The 
 vomiting of convalescence is due to some complication or to hysteria. 
 In the latter instance, it rapidly yields to the usual procedures. 
 Finally, in consequence of diphtheria, vomiting may depend upon 
 gastric paralysis. It then occurs in the form of regurgitations. In 
 this case lavage may cause death. The introduction of a considerable 
 amount of fluid into the stomach has at times been followed by the 
 rejection of matters which have passed into the respiratory truer. 
 The patients should, therefore, be given small quantities of food, 
 preferably concentrated aliments like thick bouillon. Coincidcntly. 
 the treatment of paralysis is to be instituted, strychnine given if 
 the urine does not contain albumin, and electricity employed. 
 
 In the course of infections the intestine is disturbed more than 
 the stomach. Two morbid manifestations are especially important : 
 constipation and diarrhea. For the treatment of constipation 
 preference should be given to intestinal lavage. If. at the same 
 time, hyperthermia is present, cold enemas may be prescribed, which 
 have the advantage of abstracting heat. In many cases it is well 
 to give an enema morning and evening. The patient may even be 
 instructed to retain the evening enema. This procedure has the 
 advantage of allowing the water to penetrate the organism and. at 
 the same time, softening the fecal matters, which may more readily 
 be evacuated by the enema of the following morning. 
 
 We cannot dwell upon the indications of the various kinds of 
 enemas or upon the conditions in which purgatives are to be 
 preferred. There are special rules for each infection. It is well. 
 
 53 
 
834 INFECTIOUS DISEASES. 
 
 however, to remember that a good many physicians dread purgatives 
 in the course of eruptive fevers and erysipelas. In fact, it is better 
 to prescribe enemas or lavage through a tube. If their action is 
 found insufficient, a very mild purgative may be given. In this 
 connection castor oil gives satisfactory results. 
 
 Constipation may be accompanied by intestinal paresis expressed 
 by tympanites. In this case very hot or very cold applications 
 should be made to the abdomen. There may at the same time be 
 introduced into the rectum a catheter, which soothes the patient 
 considerably by facilitating the expulsion of gases. Constipation 
 should not always be combated. In certain abdominal lesions, in 
 typhoid appendicitis, and in peritonitis it is a sort of salutary 
 reaction, and is clue to intestinal immobility which prevents exten- 
 sion of the lesions. Here an important problem faces us: we must 
 either immediately intervene and extirpate or open the morbid 
 focus, by a surgical operation, or else follow an expectant course, 
 and therefore respect the constipation, and at times even increase 
 it by means of opium. 
 
 Diarrhea is sometimes to be respected and even favored by means 
 of purgatives. Sometimes it must be checked. The treatment is 
 to be guided by an accurate diagnosis. In typhoid fever the employ- 
 ment of purgatives is of service, especially at the beginning and at 
 the end of the disease. At the beginning calomel may be given; 
 at the end, when diarrhea persists, or when it occurs at the beginning 
 of convalescence, attended by some febrile movement, a saline 
 purgative produces excellent effects. The action of purgatives 
 during the stationary period is more contestable. They are said to 
 increase meteorism and favor perforations. I believe this opinion 
 not to be well founded, and think that in most cases a saline pur- 
 gative may be prescribed every five or six days. Moreover, this is 
 an excellent means of accomplishing intestinal antisepsis. For the 
 same reason a purgative also succeeds in the majority of infectious 
 diarrheas. When, however, the general state of the patient is grave 
 and the alvine evacuations are abundant, giving rise to cold, spasms, 
 and cyanosis, I believe it is better to employ antidiarrheal substances, 
 such as subnitrate of bismuth. This is given by the mouth in doses 
 of from 4 to 6 grams, and, if necessary, from 10 to 20 grams may 
 be introduced into the intestine through a tube. This furnishes a 
 dressing comparable to that practised for the stomach. Bismuth 
 is generally associated with some insoluble antiseptic, and the treat- 
 
THEBAPEUTI08 OF TNFEOTIOUS DISEASES. 
 
 tnent is completed by the administration of milk mixed with lime- 
 water, rice, and some stimulants, uch s tea with rum, and ether, 
 bo which injections of camphorated oil may be added in grave c 
 
 Whether purgatives or constipating medicines are resorted '<>, it 
 is always advisable a1 the same time to utilize enemai and still 
 better profuse intestinal irrigations with boiled salt-water or anti- 
 septic substances. The putrefied substances and microbe* are thus 
 mechanically thrown out. 
 
 Gastrointestinal disturbances readily involve the liver, in mosl 
 cases it will suffice to continue the general treatment. Profuse 
 intestinal irrigations with cold water a1 53.5° or 59 I , I L2 or L5 ' 
 a,s well as an absolute milk diel and cold baths, are particularly 
 to be insisted upon. As ;i more special medieinc we may cite calomel \ 
 a small dose of 1 or 2 eg. given every morning produces satisfactory 
 results. The special action of ether upon the liver has already been 
 explained. Let us add the role of salicylic acid and its derivatives, 
 notably salol. This medicine has the triple advantage of being 
 cholagogue, of decreasing the pain produced by inflammation of 
 the biliary passages and of realizing a relative antisepsis in these 
 passages. In cases of renal lesions the salicylates are not well borne. 
 Hence, benzoate of soda should be substituted therefor. 
 
 Treatment of Renal Disorders. Alterations of the kidney in the 
 course of infections often embarrass therapeutics by contraindicating 
 the employment of certain active medicines. These lesions may be 
 treated by revulsion at the beginning, or by dry or scarified cupping 
 applied to the lumbar region. If hematuria appears, ergotin or, 
 still better, calcium chloride, is given. Then the oxidizing method 
 is resorted to ; from 2 to 6 grams of benzoate of soda are prescribed. 
 It is understood that the patient is to be put on an absolute milk 
 diet. In many cases satisfactory results will be obtained by dimin- 
 ishing the formation of autogenic poisons by means of antisepsis and 
 profuse irrigation of the intestine. 
 
 Albuminuria, which sets in during convalescence, is to be treated 
 as during the stationary period. "When it becomes chronic the 
 milk diet cannot be prolonged indefinitely. ^While some patients 
 bear it well, others experience marked disgust and vomit the milk 
 every time they take it. 
 
 The diet must then be modified. Coffee or rice may be added to 
 milk, some vegetables, eggs, and. if desirable, white meat may be 
 permitted. Instead of bread, dry toast should be given. In general. 
 
836 IXFECTIO US DISEASES. 
 
 diuretics are useless. If any are to be used, theobromin should be 
 prescribed. It is better to favor diuresis indirectly by cold enemas, 
 oxidants, and especially benzoate of soda. In certain cases tannin, 
 if it is well borne by the stomach, proves serviceable. Stronger 
 medicines seem to be contraindicated. In a case of albuminuria 
 with a slow course, consecutive to scarlet fever, the author prescribed 
 one drop of tincture of cantharides. This little dose sufficed, how- 
 ever, to produce hematuria and aggravate the previous symptoms. 
 
CHAPTER XXIV. 
 HYGIEN'IO AND PROPHYLAXIS OF ENFECTTOUS DISEASES. 
 
 [ndividual Hygiene, Isolation of the Patient. Precaution to be Taken b 
 
 Waiting upon the Patient. Bygiene of the Sick-room. l»i infection of thi Bedding 
 and Linen. Sterilization and Destruction of Secretions, Excretion ,and Squamata 
 Cleanliness. Alimentation. Beverages. Hygiene of ConvaL Social Hj 
 
 giene. Quarantine. Isolal ion Hospitals. Transfer of Contagiou ' B I Declara- 
 
 tion of Contagious Diseases. Municipal Service of Disinfection. Vaccination. 
 
 Variolization. Syphilization. Vaccine. Personal Statistics Showing » lie Lnflui 
 of Vaccine upon the Course of Variola. Vaccination by Mean of Atten I 
 Viruses. Anthrax Vaccine. Vaccination against Hydrophobni. Vaccination by 
 Moans of Sterilized Cultures. Attempts at Immunization ;igain-t Cholera and 
 Typhoid Fever. Prophylactic Injections of Serum. Application of the Serum 
 Method to the Prophylaxis of Diphtheria, Puerperal Fever, Tetanus, and Bubonic 
 Plague. Conclusions. 
 
 Individual Hygiene. 
 
 Hygiene of the Sick Room. The therapeutics of infectious dis- 
 eases, notwithstanding its considerable interest, is perhaps less impor- 
 tant than the hygienic measures which must be observed with refer- 
 ence to the patient and those surrounding him. 
 
 In the case of a contagious disease, perfect isolation of the patient 
 is the first requirement to be met. To this end it is necessary to 
 have two rooms at one's disposal, one in which the patient will lie; 
 another, contiguous thereto, which will serve for disinfection of per- 
 sons who have approached the patient and the objects which have 
 come in contact with him. In certain instances it is preferable to 
 have a suite of three rooms, two of which will serve the patient, one 
 during the day, the other during the night. The number of persons 
 charged with the care of the patient should be at least two, and it 
 is indispensable that these persons should have no other occupation 
 and fulfil with accuracy the prophylactic measures indicated to them. 
 
 Before entering the room of the patient the visitor should put on 
 a blouse, and it is well to protect the hair by means of a cap, and to 
 change the shoes. If the last-named precaution is not taken, it will 
 be necessary to spread in the disinfection room a crash of several 
 thicknesses, which has been sprinkled with a 2 : 1000 solution of 
 corrosive sublimate, on which the shoes should be rubbed on passing 
 
838 IXFECTIO US DISEASES. 
 
 out oi the 1 mtient s room. Then the face and hands should be washed 
 with a 1 : 2000 solution of corrosive sublimate or 1 : 1000 solution of 
 oxycyanide of mercury; if the person wears a beard it is indispen- 
 sable to cleanse it well with the same fluids. Persons waiting upon 
 the patient should never eat or drink in his room. The meals should 
 be taken in another room after having changed the clothing and 
 disinfected the hands and face. They should not carry their hands 
 to their face without being disinfected, and the handkerchiefs which 
 they may have to use in the patient's room should not be used out- 
 side. It is also indispensable for a parent to abandon the unwise 
 habit of kissing the patient: they should avoid every unnecessary 
 contact with the patient. 
 
 The sick room should be large and well ventilated, with southern 
 or eastern exposure. The windows should be furnished with Venetian 
 blinds, which are to be kept closed in certain infectious diseases, such 
 as measles, variola, and sometimes erysipelas. The red glasses advo- 
 cated by Finsen for the treatment of variola, and at times employed 
 in measles, do not seem to be useful. Red light often exerts a too 
 intense excitation upon the nervous system, while green light seems 
 to be better borne. The hangings of the room should be removed, 
 as well as all useless objects and curtains. The bed of the patient 
 should be placed in the middle of the room, or at least far from the 
 walls, so as to be approached from any side. There should be, espe- 
 cially in cases of obese patients, some contrivance designed to enable 
 the nurses to raise the patient easily for cleansing without tiring 
 him. If the skin shows a tendency to develop bed-sores, the bed- 
 clothes should be sprinkled with talcum or cinchona powder, and 
 pneumatic rings or water cushions should be used. 
 
 When possible two beds should be placed, with a bath-tub between 
 the two. When the patient has taken a bath he should be put in 
 the second bed and, while he is resting there, the other bed should 
 be aired and properly arranged. In this manner after each bath the 
 patient may lie down in a comfortable bed. The physician should 
 pay particular attention to the ventilation of the room. In summer 
 the windows may be left open for the greater part of the day. During 
 the night the window of the adjoining room is to be left open, and 
 a screen should be placed so as to protect the patient from the 
 draught of cold air. In winter the ventilation of the room should 
 be assured by means of an open fireplace, where a fire should be kept 
 up night and day. For ventilating the room the window of the 
 
HYGIENE ANI> PR0PHYLAXI8 OF INFECTIOUS DI8EA8E8. 839 
 
 adjoining room should be opened, [f h i very cold, the latter room 
 must also be heated ; while the window is open the door between the 
 two rooms should be kepi closed. The temperature of the sick-room 
 should not, he very high; it should be kepi between 61° and 64° I 
 (16° and L8° 0.). 
 
 Cleansing and Disinfection of the Room and Objects; Sterilization of 
 
 Morbid Products. 'The cleansing of the room hould not be made by 
 sweeping, which raises dust, hut by means of a mop wel with .'i solu- 
 tion of corrosive sublimate. 
 
 According to the disease treated, the patienl may be permitted to 
 riso to attend to his natural wants, or the bed-pan may be employed. 
 This measure is indispensable in typhoid fever. The dejecta musl 
 always be disinfected before they are disposed of. A 2: L000 solu- 
 tion of corrosive sublimate, or a 50; L000 solution of copper sulphate, 
 or lime-water, should he poured into the bed-pan. The mine should 
 be collected in the adjoining room, and after the amount voided in 
 twenty-four hours is measured, it should be disposed of. In certain 
 cases, however, it is advisable to disinfect the urine. The urine in 
 hemorrhagic variola and thai of typhoid patients, when they contain 
 albumin and the germs of the disease, are so to be treated. The 
 various discharges and secretions are to be taken upon absorbent 
 cotton and thrown into the fire. The sputa must be disinfected by 
 means of antiseptics or boiling. If there is desquamation, the 
 squamata that fall in the bed-clothes should be burned. If any should 
 fall on the floor, they should be picked up by means of a wet cloth. 
 The patient should have exclusively his own eating utensils. These 
 should be cleansed in the adjoining room, first plunging them into 
 boiling water. The instruments serving for the usual explorations, 
 such as the tongue depressor or the spoon substituted for it in 
 examining the throat, should also be sterilized. In our wards we em- 
 ploy glass tongue depressors, which are very easily sterilized. Of 
 course, the various canulas, catheters, as well as thermometers, 
 should also be disinfected. It is advisable to immerse all the linen 
 of the patient in an antiseptic fluid, thus preventing the possible 
 dissemination of dried products and squamata until they are sent 
 away for disinfection. A solution of lysol serves this purpose well. 
 
 During the course of the disease, and especially during convales- 
 cence, the patient often asks to write. If his desire is to be complied 
 with, the paper should be sterilized by means of sulphur Or formol 
 vapor. "When he begins to get up he must put on clothing which 
 
840 INFECTIOUS DISEASES. 
 
 may be disinfected afterward. Finally, after a certain period of time 
 he may be permitted to resume his ordinary occupation. It is diffi- 
 cult to determine at what moment a convalescent individual is no 
 longer contagious. The period of isolation has been fixed at sixteen 
 days in measles, varicella, and mumps, and at fortjr days in scarlet 
 fever and variola. These averages are acceptable. The author 
 believes, however, that the quarantine in cases of measles may, with- 
 out any inconvenience, be reduced. For varicella and variola, isola- 
 tion may be abridged in mild cases, when there are only a few eruptive 
 elements and the desquamation is complete. On the other hand, 
 after a confluent variola, if the crusts persist at the end of forty days, 
 the danger of contagion has not yet disappeared, and isolation must, 
 therefore, be prolonged. 
 
 In case of diphtheria, cultivation is often resorted to; as long as 
 Loeffler's bacillus is found isolation is to be maintained. If at the 
 end of three weeks the microbe has disappeared, an inoculation into 
 the guinea-pig is advisable. These precepts are perhaps good, but 
 they have the great inconvenience of not being sufficiently practical. 
 One may, therefore, be contented with isolating the patient for three 
 weeks, then he should be advised to practise for at least a month, 
 morning and evening, cleansing of the mouth by means of boiled 
 water to which thymol is added in the proportion of 1 : 1000. 
 
 When it is thought that the patient needs no longer to be isolated, 
 he must be given in the adjoining room a last antiseptic bath with 
 corrosive sublimate or naphtol. If possible, his hair should be cut 
 very close; at all events, complete cleansing of the scalp with soap 
 and then with some antiseptic water should be made, this to be 
 followed by rubbing with alcohol. After the bath, the patient should 
 put on clean clothing, and leave definitely the rooms in which he has 
 been treated. These rooms are then to be disinfected by means of 
 hot corrosive sublimate solutions or vapors of sulphur or formal- 
 dehyde. In our wards, after cleansing with corrosive sublimate, we 
 burn 30 grams of sulphur per cubic metre of space. The locality is 
 kept closed for twenty-four hours. Moreover, all objects of little 
 value which have been used by the patient, such as toys and books, 
 should be burned. It is understood that domestic animals must not 
 be allowed to enter the patient's room, for their hair becomes charged 
 with infective products, which may then be easily disseminated. 
 
 Hygiene of the Sick. During the course of infection cleanliness 
 of the patient must be constantly attended to. If there is no special 
 
iiy<ui<;ni<; and PROPHYLAXIS OF INFECTIOUS DISEASES. h\\ 
 
 reason for the employment of balneotherapy, it i advi able, 
 hygienic measure, fco give the patienl s lukewarm bath of fifteen or 
 twenty minutes every day or every other day. Alter each meal the 
 mouth of the patient musl be cleansed. After each injection the 
 urinary organs and anus should be cleansed. Likewise, the mouth 
 is to be cleansed every morning with Vichy water or borated solution, 
 the teeth brushed, and a small amounl of mentholated pomatum 
 
 introduced into the nostrils; the CUtaneoUS abrasiOM nui-t he di< 
 
 and, in case of desquamation, a little vaselin should he 3preadupon 
 
 the skin. It is also very useful to prescribe daily one or two enemas 
 in order to cleanse the lower portion of the intestine. A little 
 caution which should not he overlooked ;it the beginning of infectious 
 diseases is to remove the jewels, rings, and ear-rings of the patient. 
 In case of erysipelas, ear-rings may give rise to ;i sphacelus in the 
 inflamed lobe. In several cases the author has seen the finders- 
 swollen under the influence of the variola erupt ion and so strangu- 
 lated by rings that the cutting of those ornaments became a diffi- 
 cult matter. 
 
 Alimentation. As has already been stated, patients must be fed 
 during infections. As a general rule, they should be given milk, 
 bouillon, and a certain amount of beverage, but care should be taken 
 to give a very small amount of liquid each time. The best practise 
 is to give a glass or a glass and a half of milk every hour. Vichy, 
 lime-water, or pancreatin may be added to the milk. If this nourish- 
 ment is not kindly borne, a little beer-yeast ma}- be given, or the 
 milk may be replaced by some other substitute. (See footnote, 
 page 832.) The amount of milk varies according to the case: it may 
 be said to be for an adult two quarts (two litres) a day. In cases 
 of scarlatina milk must be the only aliment : no bouillon is to be 
 permitted, but some beverages sweetened with syrup of currant or 
 pomegranate, or sweet barley-water. The milk diet being absolute, 
 three quarts of it must be given daily for twenty days. At the end 
 of this time if the urine contains no albumin a more substantia] 
 alimentation may be resumed, such as bouillon, rice, creams of vege- 
 tables, eggs, and, four or five days after, even meat may be given. 
 Should some albumin appear in the urine, the absolute milk diet 
 should again be instituted, which is to be discontinued eight or ten 
 days after the disappearance of albuminuria. 
 
 In most other diseases, including typhoid fever, two quarts two 
 litres) of milk and one quart (one litre) of bouillon are generally 
 
842 IXFECTIOUS DISEASES. 
 
 given. Dr. Robin also prescribed beef-tea prepared by heating small 
 pieces of meat with one quart (one litre) of bouillon in a double 
 boiler. In order not to coagulate the albumins, care is to be taken 
 not to raise the temperature above 140° F. (60° C). Bouillon has 
 the advantage of acting as a peptogen and, at the same time, intro- 
 ducing into the organism salts to compensate for the loss of mineral 
 matters. The amount of salts is from eight to ten grams in a litre 
 (1000 c.cm.). Vegetable infusions may likewise be utilized. A very 
 good preparation consists in mixing one part of barley-water with 
 two of milk; this is preferably sweetened with honey. This mixture 
 is often very well borne by those who do not like milk. When, how- 
 ever, the repugnance for milk, experienced by some patients, cannot 
 be overcome, one is compelled to resort to some other alimentation. 
 Bouillon and also bouillon with an egg added to it (lait de poule). 
 It is well to complete the diet by a small amount of alcoholic bever- 
 ages: according to the case, vinous lemonades, Malaga or Bagnols 
 wine, and Todd's potion. Coffee may also be permitted in the pro- 
 portion of 10 grams for 200 grams of water. 
 
 The diet above indicated has not seemed sufficient to certain physi- 
 cians who at present nourish their patients substantially. As a 
 matter of fact, three or four quarts (three to four litres) of milk must 
 be given in order to meet the wants of the economy. So great a 
 quantity is too much for some patients to bear. Moreover, milk 
 contains an inadequate proportion of albumin and carbohydrates, 
 and an excess of fat. It is necessary to increase the administration 
 of nitrogenous aliments. This is what was done by the addition of 
 bouillon. At present several Russian physicians go farther. Dr. Va- 
 quez, who has tried the new method in typhoid fever, advises a cup 
 of milk every other hour only; at 8 a.m. he gives, instead of milk, 
 cafe au lait or a soup with milk, and some flour or rice. At noon 
 and at 6 p.m. milk is replaced by a meal composed of some soup or 
 a bouillon containing the yolk of an egg and a small cup of meat 
 jelly, or fresh meat juice. At the end of the disease, raw meat, 
 preferably chopped mutton, is given. Two or three days after the 
 fall of the fever, creams of vegetables are given, and toward the 
 eighth day eggs, dry toast, and stewed fruits are allowed. 
 
 By thus nourishing the patient, we succeed in preventing adynamic 
 manifestations and abridging considerably the period of convales- 
 cence. Intestinal disturbances, perforations, hemorrhages, and con- 
 sequent relapses were feared; according to published observations, 
 
IIYUIHNH AND I'JiOI'U YLAXIS OF INFECTIOUS DI8EA8ES. 843 
 
 however, this apprehension is not well founded. The feeding having 
 been continued during the entire course of the disea e, itt incri 
 at the time of convalescence gives rise to nodi order. On the con- 
 trary, Lt is known how frequenl are relapse* in those ca <• which are 
 subjected to milk diet, when the patient are too oon permitted to 
 take substantia] food. 
 
 Barring the case of typhoid fever, the author thinks thai in .-ill 
 oilier infections excepl scarlatina ;i sufficiently plentiful and varied 
 alimentation may be allowed without any fear. The author gives 
 milk, bouillon, eggs with soups and particularly hurley and rice soup, 
 according as (here is tendency to constipation or to diarrhea. This 
 diet seems to him especially importanl in variola. Mi- experiments 
 demonstrated that abundanl alimentation often enables animals to 
 resist the inoculation of variola. In some cases, however, we may 
 have some difficulty in overcoming the resistance of patients whose 
 throats are covered with pustules and who suffer when they swallow 
 food. In such cases, gargling with an infusion of cocoa Leaves should 
 be prescribed or the throat painted with a cocaine solution before each 
 meal. Should these methods fail, the patient should he fed by means 
 of a tube introduced through the nose. Should albumin appear in 
 the urine the patient should be put on milk diet, eggs, and rice. The 
 same alimentation, with the same restrictions, is to be employed in 
 diphtheria. During convalescence the patient should be given more 
 liberal nourishment. If there are renal complications and albumin 
 in the urine, the diet should be limited to milk, coffee, raw eggs, and 
 rice, a small amount of farinaceous food in the form of puree and 
 stewed fruits. No meat is given, and instead of bread, dry toast. 
 If paralysis of the palate develops, notably as a result of diphtheria, 
 purees are the aliments most readily accepted by the patient. He 
 must be advised to swallow the liquids with the head thrown back, 
 and to drink very slowly, lying on his back so as to cause the fluids 
 to flow T according to the laws of gravitation. 
 
 In conjunction with the aliments a certain amount of beveragi - - 
 to be allowed. The thirst experienced by the patient clearly in< licates 
 that his organism wants water. Slight infusions, sweetened, should 
 be given. Milk not being sufficiently rich in carbohydrates, it is well 
 to put sugar in the beverages. For the same purpose boiled lemon- 
 ades, vinous lemonade, and some Vichy may be given with a little 
 syrup. If the stomach does not tolerate fluids well, the beverages 
 should be replaced by enemas, which the patient must retain. In 
 
844 INFECTIOUS DISEASES. 
 
 such cases subcutaneous injections of artificial serum yield gratifying 
 results. 
 
 Hygiene of Convalescents. During convalescence, diet is to 
 receive special attention. Nourishment must be progressively in- 
 creased and the patient gradually allowed to return to his habits in 
 the matter of eating, but the digestive functions must be carefully 
 watched. If flatulence, slow digestion, hypochlorhydria or hyper- 
 chlorhydria occur, the various classical treatments of dyspepsia should 
 be employed. The intestinal function also requires attention. Exag- 
 geration of gastrointestinal putrefactions, constipation, and diarrhea 
 and mucomembranous enteritis are not rare in consequence of infec- 
 tions. At all events, the convalescent must be instructed to eat 
 slowly and masticate well, and take at least four meals daily. After 
 each meal he must take a rest for an hour, either sitting or lounging, 
 and a little more covered than usual, since a convalescent is more 
 sensitive to cold than normal subjects. It is, therefore, advisable to 
 give them warmer clothing and to have their room at a higher 
 temperature than usual. The room must be well ventilated: in 
 summer the windows should always be kept open, and during the 
 night those of the adjoining room. Exercise must be moderate and 
 progressive. It will be useful for a certain length of time to continue 
 to take the rectal temperature, at least in the evening. An eleva- 
 tion in the temperature often announces that alimentation is not 
 well borne or that exercise has caused too much fatigue. When 
 convalescence is well established it is desired, whenever possible, to 
 send the patient to a summer or winter resort, according to the 
 season. 
 
 The author cannot too much emphasize the necessity of devoting 
 continued attention to the toilet. A convalescent should take 
 slightly tonic sulphur or salted baths. He must rub his body every 
 morning for five minutes with a Turkish towel or rough flannel wet 
 with some alcoholic preparation, for example, lavender brandy. In 
 order to be able to judge the efficacy of these measures, it is advisable 
 to weigh the convalescent once a week and examine his strength by 
 means of the dynamometer. If the functions are not re-established 
 with gratifying rapidity, bitters should be prescribed in case of ano- 
 rexia, and tonics, such as lecithin, in case of weakness. In such cases 
 subcutaneous injections of artificial serum are also practised. Finally, 
 the alimentary method may be modified, and raw meat, for instance, 
 may be recommended. 
 
JIYaiKNK and morn y LA x is OF INFECTIOUS DISEASES. 845 
 
 Social Hygiene. 
 
 The advice above presented with reference to the hygienic tri 
 merit and isolation of patients is not alwa;. o! application. In 
 
 order to isolate a contagious case, two person bould be a igned to 
 his service exclusively. Among the poorer cla i when 
 individuals occupy one room, isolation is impossible. Wha1 further 
 aggravates the situation is thai patients are attended by parents, 
 friends, an<l sometimes Hie janitor, and thai personf thu approach 
 ing the patient return to their occupations without taking any anti- 
 septic precautions. Hence, epidemics ravage the crowded sections 
 of cities and make certain tenement-houses centre;- of infection. 
 
 While certain laws have been promulgated for preventing the 
 importation of epidemics from foreign countries, hardly any meas- 
 ures have been taken to insure isolation of contagious patients in 
 domestic epidemics. The only progress up to the present time real- 
 ized in France has been the establishment of services of disinfection, 
 of vaccination at home, and of transportation of contagious patients 
 in special vehicles and urban ambulances. It is, of course, out of the 
 question to isolate all contagious cases. Only those individuals who 
 suffer from acute infections may be isolated in appropriate institu- 
 tions. When the question is one of chronic infection, such as tuber- 
 culosis, other measures are applicable. A fight against the latter 
 disease has been undertaken with gratifying results. The public is 
 warned by means of placards in public establishments, surface car.-, 
 wagons, not to spit upon the floors, and in a good many establish- 
 ments hygienic cuspidors have been placed; public lectures and popu- 
 lar books on tuberculosis have been published. Moreover, sanitariums 
 and rural colonies have been created. There are already more than 
 a hundred of these in France alone. 
 
 Declaration of Contagious Diseases; Disinfection by Officers of 
 the Board of Health; Transportation of Patients. The law i if Novem- 
 ber 30, 1892, obliges every physician, under penalty of the law. to 
 pay a fine of from fifty to two hundred francs to declare to the public 
 authorities the cases of contagious diseases coming under his obser- 
 vation in the course of his practice. The present list includes the 
 following twelve diseases: typhoid fever, typhus fever, variola and 
 varioloid, scarlatina, diphtheria, sudor anglicus, cholera and choleri- 
 form maladies, bubonic plague, yellow fever, dysentery, puerperal 
 infections, and ophthalmia of the newborn. Certain milder infec- 
 
846 INFECTIOUS DISEASES. 
 
 tions, such as mumps, varicella, and whooping-cough, have been left 
 out, as also others that are not very contagious, such as erysipelas, 
 or are contagious for a short time only, such as measles. It would, 
 however, be advisable to add pneumonia to the list. 
 
 When patients ask to be treated outside of their homes they are 
 transported in particular vehicles and their residence is disinfected 
 free of charge — these are gratifying advances. It seems to the 
 author, however, that it is high time to take serious prophylactic 
 measures, and thus complete the law of 1892. It is necessary to 
 determine in what diseases isolation shall be compulsory. When the 
 residence of the patient does not permit isolation under sanitary 
 precautions, such cases should be transported to a special hospital. 
 It is also necessary to determine the average duration of contagious- 
 ness and engage the civic responsibility of every individual who 
 places himself in a position to directly or indirectly contaminate 
 his fellow citizens. 
 
 Finally, there remains a last question. There is a fearful disease 
 against which we possess an infallible prophylactic means, namely, 
 variola. The measures indicated above should be completed by a 
 law bearing on compulsory vaccination. We are thus led to the 
 study of a question which, from a sociological standpoint, is of prime 
 importance, that is the question of vaccination. 
 
 Vaccinations. The term vaccinia, which signifies disease of the 
 cow, primarily designated an eruptive infection afflicting cows and 
 horses, which is transmissible to various animal species and notably 
 to man, confers upon the latter immunity from vaccinia and 
 variola. Vaccination is the inoculation into man, with a prophy- 
 lactic view, of the disease of the cow. The sense of the term has 
 gradually been broadened considerably, and to-day under the name 
 vaccination are included the various methods which are capable of 
 conferring immunity against a future infection or preventing the 
 development of a disease while at its stage of incubation. 
 
 At present we are acquainted with a number of methods which 
 enable us to confer immunity and thus practise preventive medi- 
 cation. For the convenience of description the principal procedures 
 advocated may be grouped under six classes: 
 
 1. We may inoculate the disease against which we wish to preserve 
 the individual. This method, the most ancient of all, has been 
 utilized against variola. It was proposed by Auzias-Turenne against 
 syphilis. It is still employed in veterinary medicine for protecting 
 
HYGIENE AND PROPHYLAXIS OF INFECTIOUS DISEASES. - 17 
 
 animals from symptomatic anthrax, murr (fool and mouth disei 
 and peripneumonia. 
 
 "2. A benign disease may be inoculated to pre erve the ndividual 
 from a grave disease. Such is the case with vaccinia, which i 
 to be a disease different from variola and pre erve the individual 
 from the latter. 
 
 In (he two preceding cases .'i non modified virus i- introduced 
 into the organism. 
 
 ',\. The third method consists in inoculating a vim.- which bas 
 boon partially freed from its noxious properties. This method is 
 often designated Pasteurian vaccination. It i- employed ae a pro- 
 phylactic in animals, notably againsl anthrax, and \\ith ■•' thera- 
 peutic view in man, especially againsl hydrophobia. 
 
 4. Instead of inoculating attenuated although still living microbes, 
 the products secreted by bacteria may be employed, as is often done 
 in laboratories. Such is the method initiated by Ferrari againsl 
 cholera, and which is utilized by Ilaffkin against bubonic plague. 
 
 5. Having remarked the analogy existing between the action of 
 certain toxins and that of certain substances of vegetable origin, 
 Peyraud endeavored to learn whether some poisons of a more or 
 less definite chemical character could not preserve from infections. 
 These chemical vaccinations might bo utilized against tetanus and 
 hydrophobia. Strychnine is expected to confer immunity from the 
 former of these two infections, and the essence of tansy from the 
 latter. 
 
 6. Finally, therapeutic serums are not merely curative: they may 
 be utilized as preventives. Antidiphtheritic, antitetanic, anti- 
 streptococcic, and antibubonic serums have been employed for this 
 purpose. 
 
 Immunization by Means of Strong Viruses. "\ ARIOLIZATION AND 
 Svphilizatiox. Variolization is a very ancient method which has 
 come to us from China. It was first introduced into Persia, thence 
 into Turkey, in 1673, by E. Timoni and J. Pylarini. In 1721 the 
 wife of the British ambassador in Constantinople, Lad}- Montague. 
 who saw the fairly satisfactory results obtained by this procedure, 
 brought it to the knowledge of her friends on her return to London. 
 The new method spread quite rapidly, and was very happily modified 
 by two Scotch farmers, Suttey brothers, who invented subcutaneous 
 inoculations. Inoculation of the variolar virus commonly induces 
 a benign disease. It is not difficult to comprehend the difference 
 
848 iyFECTIO US DISEASES. 
 
 which separates the evolution of the inoculated disease from that 
 of the spontaneous malady. In the case of inoculation the patho- 
 genic agent is introduced beneath the skin — i. e., into a region that 
 is not favorable to its development. As a matter of fact, the spon- 
 taneous disease probably results from inoculation into the respiratory 
 apparatus. The result is analogous to that observed when the virus 
 of tuberculosis or even of glanders is introduced beneath the skin ; 
 the infection is exhausted in local symptoms, and with difficulty 
 invades the entire economy. On the other hand, immunizing inocu- 
 lation is practised upon normal individuals who are in good health 
 and in nowise predisposed to infection. On the contrary, the 
 spontaneous disease attacks debilitated individuals, or at least those 
 whose resistance is weakened by a series of predisposing or auxiliary 
 causes. Variolization, however, is not always harmless; the inocu- 
 lated organism may be found in such conditions of predisposition as 
 to favor generalization of the infection, which may then assume a 
 serious course, and at times terminate fatally. Moreover, even if the 
 inoculated individual resists, the few pustules which develop may 
 become the means of propagation of the infection, and thus constitute 
 a danger for others. A starting point of an epidemic may thus be 
 created. 
 
 Although variolization has rendered some service, it must be 
 abandoned at present and give way to vaccination. Can the method 
 be applied to other diseases? We have above alluded to syphilization. 
 As is known, Auzias-Turenne endeavored, in 1844, to accomplish 
 with regard to syphilis what was done for smallpox. At that time, 
 however, soft chancre was not differentiated from the indurated 
 variety. The virus of the soft chancre was inoculated. Auzias- 
 Turenne injected pus and repeated the inoculations. There came 
 a moment when at least a relative immunity was acquired : the soft 
 chancre no longer developed or appeared under a mild form, and the 
 author believed he had thus conferred immunity against syphilis. 
 When, in the Congress of 1867, it was pointed out to him that he 
 had inoculated a virus different from that of syphilis, Auzias- 
 Turenne modified his theory. On the ground of the immunity 
 conferred by vaccine against variola, he argued that the virus of 
 soft chancre may immunize an individual or cure him. Experiments 
 failed to verify this conception. Individuals who were inoculated 
 a great number of times — 287 times in a case of Danielssen — con- 
 tracted the indurated chancre when the syphilitic virus was em- 
 
"HYGIENE AND PROPHYLAXIS OF INFECTIOUS DISEASES. .- r.i 
 
 ployed. Sperino's idea of combating syphilis by mean of repeated 
 inoculations with the virus of both soft and indurated chancri 
 not yielded any better results. The method was therefore aban- 
 doned. Us failure should not, however, lead tu to overlook the 
 fact that Auzias-Turenne pursued interesting experiments on 
 animals and that he bad the honesty to begin upon himself the 
 researches which he wished to pursue on man; finally, although he 
 failed from a practical standpoint, he se1 forth some interesting 
 considerations, and seemed to have a foresigh.1 of exaltation and 
 attenuation of viruses. 
 
 At present n<> strong viruses are inoculated into man, bu1 they 
 tire inoculated into animals. This is (lie principle of the method 
 employed against symptomatic anthrax, murr (foot-and-mouth 
 disease), and peripneumonia. In order to render the inoculation 
 inoffensive, it is practised in those regions of the body in which a 
 thick cellular tissue offers a certain resistance to the multiplication 
 of the pathogenic agents. 
 
 Antivariolar Vaccination. The inconveniences of the preceding 
 methods are no longer found in the case of vaccinia. 
 
 It had long been known in certain regions of England, and notably 
 in the county of Gloucester, that individuals breeding cows often 
 presented in their fingers small pustules contracted on contact with 
 animals afflicted by cowpox, and that this eruption conferred upon 
 them immunity from variola. In 1768 Sutton and Fewster drew 
 attention to these facts. It was then that Jenner conceived the idea 
 of practising in a systematic manner and with a prophylactic view 
 the inoculation of cowpox. In 1798 he published the result of his 
 researches. He demonstrated the inoculability of coAvpox from cow 
 to man, and its transmission from man to man. and showed that 
 immunization was surely conferred by the inoculation of the vaccine. 
 
 The interesting question was then and still is asked: What are 
 the analogies existing between vaccinia and variola? It is certain 
 that clinically the two diseases are absolutely distinct. To be con- 
 vinced of this it suffices to examine a man attacked simultaneously 
 by both of these diseases. The objective characters of the variola 
 and of the vaccinal pustules are not at all similar. At present, 
 however, when we are well acquainted with the variability of viruses, 
 we may ask whether the differences are as great as one might believe, 
 whether vaccinia and variola do not have a single origin, and wh ether 
 the virus has not been modified through repeated passages in man 
 
 54 
 
850 ISFECTIOUS DISEASES. 
 
 and in animals. Dualists, among them Chauveau, remark that the 
 objective characters are different, that the receptivity of animals 
 is not similar, and particularly that the variolar virus is not trans- 
 formed into vaccinia through passages in cows. The latter argument 
 is not perhaps irrefutable, for it may be answered that inoculations 
 in series have not been sufficiently numerous. On the other hand, 
 the fact itself has been contradicted. Voigt (1881), Fischer (1885), 
 Eternod and Haccius (1892) assert that by practising inoculations 
 on large surfaces they have transformed variola into vaccinia, and, 
 transferring their experimental results to the domain of practice, 
 they have prepared a vaccine of variolar origin which has given 
 excellent results. 
 
 Although the question presents great theoretical interest, it seems 
 to be of little consequence from a practical standpoint. Vaccinia, 
 which seems to be weakened when it is inoculated from man into 
 man, according to the Jennerian method, preserves all its activity 
 when it is cultivated in cows. A second problem, however, arises. 
 Its human origin being denied, it remains to learn whether vaccinia 
 is originated in the cow or in the horse. Jenner supposed cowpox 
 originated from horsepox, and described the disease of the horse 
 under the name " grease." This gave rise to confusion. The word 
 "grease" was translated by the expression "eaux aux jambes " — 
 an expression applied to osteitis of the foot. It was not until after 
 the contributions of Sarrans and Lafosse that it was understood 
 that Jenner 's grease is the disease of the horse, formerly designated 
 under the name ' ' morve volante ' ' (flying glanders) . Lafosse showed 
 that the virus is readily inoculated from the horse to the cow, and 
 that it produces in the latter a typical vaccinia. Chauveau showed 
 later on that the inoculation of horsepox produces in children an 
 aborted vaccinia only ; he concluded therefrom that vaccinia acquired 
 all its activity in the cow, and that it represents a bovine infection 
 and not an infection of the horse. It is to be noted, on the other 
 hand, that vaccinia is transmissible to a great number of animal 
 species, notably to dogs, sheep, goats, and, at least in certain cases, 
 to rabbits. 
 
 At present it may be stated that the vaccinal virus, owing to 
 numerous passages which it has undergone in cows, has become a 
 fixed virus: its inoculation is almost invariable. In individuals 
 vaccinated for the first time, the eruption begins seventy-two hours 
 after inoculation, and is clearly manifest in the course of the fourth 
 day. Even with this fixed virus, however, certain variations are 
 
HYGIENE ANl> I'lun'UYLAXis OF INFECTIOUS DI8EASE8. H'j) 
 
 observed. The incubation often lasts lour or five cU ptionally 
 
 six or seven. 
 
 The inoculation is generally practised by three epidermal punc- 
 tures or, still bettor, by superficial scarifications. The eruption it 
 localized at the infected points, and i 1 i altogether exceptional to 
 sec it generalize. In the latter case the disea e assume the character 
 of a quite serious infection, accompanied by fever. Kvei ome <■:>-(■- 
 of death in young children have been reported. Tnis eventuality, 
 however, is so extraordinary thai it hardly deserve* to I"- taken into 
 account. The generalization evidently indicates a peculiar suscep- 
 tibility to vaccinia, and probably to variola. Barring these I 
 examination of (lie locnl lesion produced by inoculation liki 
 demonstrates that individuals, according to previous dl i 
 vaccinations, according to their innate or inherited characters, 
 according to a number of intercurrent circumstances, present 
 peculiar resistance or susceptibilities. The regular vaccinia begins 
 on the third day with a papule, which is transformed into a vesicle 
 on the fifth, and reaches maturity on the seventh. At this moment 
 the lesion is constituted by a large flat, umbilicated vesicle, sur- 
 rounded by a red areola and containing a clear and thick fluid. 
 Toward the eleventh day the crust appears, which is exfoliated from 
 the twenty-first to the twenty-eighth day, leaving an indelible 
 cicatrix. In certain instances the evolution is more rapid, the 
 vesicle remains small, and, within a few days, its evolution is termin- 
 ated. This vaccinoid, which has improperly been called pseudo- 
 vaccinia, simply indicates a slight resistance of the organism, and 
 it seems to me to prove that immunity requires to be reinforced in 
 such cases. 
 
 The evolution of vaccinia is followed by a modification in the 
 body fluids, which has been clearly demonstrated by the researches 
 of Sternberg, Beclere, Chambon, and Menard. This is a particular 
 instance in perfect harmony with our present knowledge of the mech- 
 anism of artificial immunity. As always, however, the modifications 
 thus produced in the organism are not permanent. At the end of 
 a certain length of time immunity disappears. It is generally 
 estimated that adults should be vaccinated once every ten years: 
 children whose nutrition is more active more rapidly lose their 
 vaccinal immunity, and must be revaccinated once every seven or 
 eight years. These data are perfectly acceptable. It should be 
 remembered, however that one vaccination does not suffice to 
 extinguish variola in a definitive maimer. The countries where 
 
852 INFECTIOUS DISEASES. 
 
 vaccination is compulsory are not free from the disease. For ex- 
 ample, in Sweden, where the mortality was 165 per 100,000 inhab- 
 itants before the introduction of vaccine, fell, since the discovery 
 of vaccination, to 55, and since vaccination was made compulsory, 
 to IS. In Germany, where law prescribes vaccination and re- 
 vaccination, the mortality is only 2.2 per 100,000 among the civilian 
 population, while in the army, in which the rules are better observed, 
 variola may be said to be unknown. It would, therefore, be easy, 
 through an international agreement, to cause the disappearance of 
 variola. So far as France is concerned, we know at present that 
 variola, although sufficient^ rare, is still observed, particularly in 
 certain cities, such as Marseilles. In 1900 we had in Paris a quite 
 severe epidemic, which continued and even increased the following 
 year. At the time an epidemic is prevailing the resistance conferred 
 by previous vaccinations should not be counted upon; variola itself 
 does not create absolute immunity. A certain number of recur- 
 rences have been reported, and Heim, by revaccinating individuals 
 who had once had variola, obtained 32 per cent, of complete suc- 
 cesses, 25 per cent, of incomplete successes, and 42 per cent, failures. 
 According to the wise advice of Dr. Hervieux, in ordinary times 
 individuals should be vaccinated at the age of ten, and then again 
 at the age of twenty. At the time of an epidemic, however, every- 
 body should be vaccinated. It is also to be remembered that the 
 aged are not refractory, as is generally supposed. Facts recorded 
 by Beclere and Brot 1 are absolutely conclusive. Everybody should, 
 therefore, be revaccinated, since the duration of immunity is not 
 fixed, and it is not known at the end of how much time it disappears. 
 Thus, in 1897, we noticed that vaccinia succeeded for the second 
 time in six children, the oldest of whom was five years and the 
 youngest sixteen months old. 2 In all of these indubitable cicatrices 
 of a previous vaccination were present. These subjects were, there- 
 fore, in a state of receptivity. Several personal observations of 
 mine could be cited in support of this conclusion. The most inter- 
 esting of these observations is that concerning a pregnant woman, 
 already referred to (p. 590), who had been successfully vaccinated 
 at the seventh month of her pregnancy, and two months later con- 
 tracted a benign variola which she communicated to her child, 
 The latter, owing to the influence of the maternal vaccination, 
 resisted the infection fairly well. 
 
 1 Brot. De Pimmunit£ vaccinale. These de Paris, 1897. 
 
 2 Roger. Sur la duree de 1'immunit^ vaccinale. Soci£t6 de Biologie, July 2, 1897. 
 
HYGIENE AND PBOPHYLAXIS OF INFECTIOUS DISEASES. 
 
 The conclusion is unavoidable: a1 timet of epidemic 
 must be vaccinated. Ai ordinary time revaccination ihould be 
 practised once every ten years. [1 I ai o to be remembered 
 if a previous vaccination does no1 Becure ab olute immunity 
 variola, it decreases the gravity of the infection and thai the i 
 tality is very low in revaccinated individuals. Of mdividuak who 
 have been vaccinated three times we have losl only three in our 
 
 wards. 
 
 The statistics of the Westham-Union Bospital, bearing upon WOO 
 eases observed from IS77 to L882, furnished the following results, 
 
 which need no comment :' 
 
 Ca • Mori 
 
 • , i • i I IT 50.4 
 
 Non-vaccinated vanola 
 
 Not well vaccinated 
 
 Vaccinated \ ariola casea 
 
 Vaccinated and re> accinated ca e ... 
 
 Dr. Delom 2 who, from this point of view, tabulated L023 obser- 
 vations taken in our hospital in 1900 and at the beginning of L901, 
 
 obtained the following results: ^ ^^ ^ ^ 
 
 . l . 77 52 
 
 Non-vaccinated . 
 
 Vaccinated once withoul success 
 
 Vaccinated once with success ' ( " ' 
 
 Vaccinated with success and revaccinated without 
 
 . inn L3 13.0 
 
 success 
 
 Vaccinated and revaccinated with success ... 89 is <_ 
 
 Vaccinated while in incubation of variola . ... 39 
 
 If the age of the individual is considered, the following interesting 
 results are obtained, which we sum up as follows: 
 
 78 
 
 7'.»J 
 21 
 
 19 
 
 S6 
 
 27 1 
 
 10.7 
 «t 
 
 1 
 
 
 
 
 Vaccinated once. 
 
 
 
 Revaccinated. 
 
 .... 
 
 Vaccinated 
 
 Age of patient. 
 
 Non-vaccin- 
 ated. 
 
 Successfully. ^lly? 8 " 
 
 Successfully. Uu ^ v eS9 ' 
 
 in incuba- 
 tion. 
 
 Cases. 
 Deaths. 
 
 - 
 
 3 
 
 - 
 
 - 
 s> 
 
 * 
 
 Cases. 
 
 1 >l'll t 1 IS. 
 
 - 
 - 
 
 - 
 
 -s. 
 
 9 
 CO 
 
 s 
 
 Deaths. 
 Per ct. 
 Cases, 
 Deal b 
 I'er ot. 
 
 - ~ ._ 
 5 - 
 
 _ - - 
 
 0- 5 years 
 
 39 
 
 28 
 
 71.7 
 
 4 
 
 1 
 
 25.0 
 
 5 
 
 3 
 
 60.0 
 
 
 
 
 
 13 6 46.1 
 
 6-10 " 
 
 1 
 
 
 
 
 
 10 
 
 2 
 
 20.0 
 
 3 
 
 1 
 
 33.3 
 
 1 
 
 1 1 100 
 
 
 
 11-20 " 
 
 4 
 
 2 
 
 50.0 
 
 68 
 
 7 
 
 10.2 
 
 3 
 
 1 
 
 33.3 
 
 8 
 
 1 
 
 12.5 14 
 
 4 1 25.0 
 
 21-30 " 
 
 19 
 
 13 
 
 68. 4 
 
 257 
 
 45 
 
 17.8 
 
 3 
 
 2 
 
 66.6 
 
 45 
 
 3 
 
 S.5 37 4 
 
 10. S 
 
 11 
 
 31-50 " 
 
 12 
 
 7 
 
 58. 3 
 
 287 
 
 75 
 
 26. 1 
 
 2 
 
 H 
 
 50.0 
 
 36 
 
 7 
 
 20.0 44 
 
 • 
 
 10 
 
 Above 50 " 
 
 2 
 
 2 
 
 100 
 
 54 
 
 29 
 
 39. 1 
 
 2 
 
 
 
 10 
 
 3 30.0 3 1 33.3 1 1 100 
 
 i Report on 1000 cases of smallpox in Westham-TJnion Hospital. Lancet. July 22, L882 
 » Delom. De Finfluence de la vaccine sur la variole. Thfee de Paris. 1901. 
 
854 INFECTIOUS DISEASES. 
 
 Although vaccination is not compulsory in France, most of the 
 inhabitants of that country have undergone at least one inoculation. 
 A certificate of vaccination is required of children to be admitted to 
 schools. All recruited men to the regiments are revaccinated. The 
 influence of the vaccinations practised in the army explains why men 
 from twenty to thirty years of age are far less frequently attacked 
 by variola than women. In large administrations revaccinations are 
 often practised. According to information, however, which the 
 author obtained during the last epidemic, private establishments are 
 often better organized from this standpoint than public establish- 
 ments. Furthermore, a measure has been adopted which seems to 
 have very gratifying results : When a case of variola is reported in 
 a house a vaccine-bearing heifer is sent to the house and employed 
 for vaccinating all the residents free of charge. Many persons who 
 would not otherwise take the trouble thus consent to be inoculated 
 at home. Owing to these various measures variola has been con- 
 siderably decreased; the epidemic, however, which recently prevailed 
 shows that it may easily again be increased. It would, therefore, be 
 advisable to do in France what is being carried out in a great number 
 of countries, notably in Germany. Two inoculations suffice, on con- 
 dition, of course, that all the inhabitants be submitted to it. One 
 to be practised during first childhood (under two years of age), the 
 other at the age of twenty years. The efficacy of the method is 
 demonstrated by German statistics. The results are so clear that 
 some authors have declared variola to be a disease of historical 
 interest, since it is no longer observed in civilized countries. 
 
 Immunization by Attenuated Viruses. Instead of introducing into 
 the organism a mild natural virus capable of conferring immunity, 
 modified infectious agents may be employed, namely, such agents 
 as have been deprived of part of their virulence, in other words, 
 attenuated viruses. Such is the principle of a new method called 
 Pasteurian vaccinations. 
 
 Attenuation may be obtained by a great number of procedures. 
 Most of these consist in cultivating the virulent agent under dys- 
 genesic conditions or disturbing its vitality by physical or chemical 
 means. The age of cultures, heating, exposure to sun rays, develop- 
 ment at high temperatures, the addition of antiseptic substances to 
 the culture medium, the influence of compressed oxygen — such are 
 the most usual procedures. Let us add to these inoculation into 
 certain animals : the virus becomes exalted for the species upon which 
 
HYGIENE AND PROPHYLAXIS OF INFECTIOUS DISEASES, 
 
 the experiment is performed, while it become attenuated a 
 another species, a result which may I"' employed a an argument of 
 the original unity of variola and of vaccinia. Bowever thu may be, 
 Pasteurian vaccinations are exclusively employed in veterinary medi- 
 cine and give remarkable results againsl anthraj B 
 various systems of vaccination againi I anthrax animale sensitr 
 this disease have successfully been rendered refractory. Everyone 
 remember* (lie famous experimenl of Pouilly-le Fort, where Pasteur 
 conclusively demonstrated the value of his method. At pri 
 there is not the slightest shadow of doubl as to the efficacy of the 
 method. From L882 to L894, 1,788,677 sheep have been vaccinated 
 in France, and their mortality has been 0.9 1 per cent ., while formerly 
 it readied 10 per cent. As regards cattle, 200,962 have been inocu- 
 lated, and the mortality has fallen from 5 per cent . to 0.3 1 per cent .' 
 Numerous laboratories of vaccination have been organized in foreign 
 countries (Vienna, .Madrid, Turin, Buenos Ayres, Odessa, etc. , and 
 their results have confirmed the efficacy of the method. 
 
 Vaccination against Hydrophobia. These results suggest the Ques- 
 tion whether vaccines could not act even after the introduction of 
 an active virus. It was likewise Pasteur who took up and solved 
 this problem. Into individuals bitten by a rabid animal are prac- 
 tised injections with the diseased spinal cord attenuated by desicca- 
 tion. A refractory state is thus created which develops more 
 speedily than the disease. Immunity is immediately manifest to 
 prevent the propagation of the active virus and enable the organism 
 to destroy it. 
 
 It was by studying the action of the hydrophobic virus and by 
 seeking to vaccinate against it that Pasteur was led to this new 
 result. It should not be forgotten, however, that the first attempt 
 of vaccination against hydrophobia is due to Gautier. In a note 
 presented to the Institute. January 25, 1881, this scientist announced 
 that the injection of hydrophobic saliva into the veins of sheep does 
 not produce hydrophobia, but confers immunity. This result, which 
 was confirmed August 1. 1SS1. in a contribution in which the author 
 announced that he had vaccinated nine sheep and one goat, wj - 
 considerable interest. Unfortunately, the method was unfit for prac- 
 tical purposes, because the introduction of saliva is an unreliable and 
 dangerous method. Intravenous injection, which succeeds so well 
 
 1 Chamberlaiul. Resultats pratiques des vaccinations coutre le charbon. Annates de 
 I'Institut Pasteur. 1894. 
 
856 ixfecti o us I) is /■:. i .s /; s. 
 
 with ruminants, in most cases causes death "when it is applied to 
 other animals, and particularly to the dog. 
 
 In 1SS1 Pasteur, Chain) >erland and Roux, and Thuillier published 
 a method which did away with all the uncertainty of inoculation of 
 saliva: This was the employment of the hydrophobic spinal cord, 
 an emulsion of which was injected beneath the dura mater. In 1882 
 Pasteur and his collaborators announced that of three dogs inocu- 
 lated two perished and one survived after having been sick this 
 animal had become refractory ; it was subsequently twice inoculated 
 by trepanation, but did not become hydrophobic. From that time 
 on Pastern' saw several dogs inoculated with virulent matter resist 
 the experiment and become refractory. He even noticed that large 
 doses of hydrophobic virus, when injected beneath the skin, produce 
 hydrophobia less frequently and immunity oftener than medium 
 doses. This result, highly interesting from the standpoint of patho- 
 logical physiology, was confirmed by various experimenters, notably 
 by Bardach. Under these conditions, however, vaccination appears 
 as an exceptional fact; it was, therefore, necessary to prepare a virus 
 incapable of killing the dog, but sufficient to increase its resistance 
 and render it refractory to more and more energetic agents. This 
 attenuation of virulence Pasteur obtained by transferring hydro- 
 phobia from the dog to the monkey. As passages are practised upon 
 the latter animal the activity of the virus weakens, a fact proved 
 by the progressive lengthening of the period of incubation. If 
 the virus is then transferred to the rabbit, it becomes exalted; the 
 period of incubation gradually decreases until the minimum point is 
 reached. 
 
 This minimum delay of incubation, obtained at about the hun- 
 dredth passage, is invariable, and amounts to six or seven days. The 
 virus is then said to be " fixed." 
 
 Thus, starting from the monkey and passing through the rabbit, 
 one may prepare a series of viruses with progressively decreasing 
 activity. If we inoculate beneath the skin of a dog the more and 
 more virulent spinal cord of a rabbit, beginning with the least 
 energetic, we produce no accident, but confer on the dog immunity 
 against the most virulent virus introduced by trepanation. This 
 result, based upon twenty-three experiments, was announced to the 
 Institute on May 19, 1884, and confirmed by the researches pursued 
 upon forty-two inoculated and forty-two controlled animals, before 
 a commission composed of Beclard, Bouley, Bert, Vulpian, and Vil- 
 
HYGIENE AND PROPHYLAXIS OF INFECTIOUS DISEASES. 857 
 
 Iciniii. When bitten by rabid dog , no1 one of the vaccinated animals 
 succumbed, while mosl of the controls perished. 
 
 The discovery was, therefore achieved, bu1 the method wat not 
 practical. It was necessary to suppress the pai age through the 
 monkey and attenuate the virus withoul employing this animal. 
 This new problem was likewise solved by Pa teurand hit collabora- 
 tors. They took rabbits which had died from the " fixed " virus,and 
 they found thai their spinal cords lost much of their virulence under 
 the influence of desiccation. In order to obtain thif result, these 
 spinal cords are detached with thegreate I a eptic precautions; they 
 are suspended in a vial closed with cotton and .'if the bottom of 
 which there are fragments of potassium. From the thirteenth to the 
 fourteenth day on, the cord is found to have losl ite virulence; 
 the shorter the period of desiccation the greater Ls the activity of the 
 conl. In 1885 Pasteur uniioiiiiceil that, l>y means of spinal cords 
 thus prepared, he had rendered fifty dogs refractory to inoculations 
 practised into the skin and even beneath the dura mater. 
 
 In view of the results given by this memorable experiment, an 
 attempt might he made to apply to man the new method. The 
 occasion soon presented itself. As is well remembered, the firsl 
 attempt was made upon young Joseph Meister, bitten July 4, 1885. 
 After consulting Professors Vulpian and Grancher, Pasteur practised 
 his mode of treatment upon this child, who seemed to be condemned 
 to certain death by the number and depth of the bites. The result 
 exceeded all expectation. The patient recovered, and sixteen ; 
 after the inoculation, he was in perfect health. 
 
 After this first case, which was reported in October. 1885, very 
 large numbers of individuals have come to the laboratories of Pasteur 
 from all parts of the world. More than ten thousand have been 
 treated in Paris; at least as many have been similarly Treated in the 
 Pasteur Institutes of foreign countries. Pasteur first employed a 
 simple method, which consisted in injecting beneath the skin the 
 spinal marrow of the fourteenth day, then successively those of the 
 thirteenth, twelfth, until the fifth day. Each specimen of marrow 
 was injected once; the treatment, therefore, lasted ten days. This 
 method was not sufficient for grave cases: hence. Pasteur abandoned 
 it and adopted the so-called intensive method, which consists in 
 repeating the inoculations, in making the vaccinations at shorter 
 intervals, and in administering more virulent marrow. The treat- 
 ment is modified according to the gravity and especially the seat of 
 
858 IXFECTIO US DISEASES. 
 
 the bites. The method is carried out as follows: A fragment of 
 spinal marrow about 3 mm. long is taken and triturated in 1 c.cm. 
 of bouillon and injected beneath the skin in the hypochondriac 
 region. The injection is somewhat painful, but gives rise to no dis- 
 turbance except in the last two days, when the puncture becomes the 
 seat of a small erythematous and itching patch. First, a specimen 
 of the marrow of fourteen or thirteen days is employed, then pro- 
 gressively the marrows of twelve and eleven until that of the third 
 day is reached, the virulence of the latter being about the same as 
 that of the fresh marrow. The quantity injected may reach 3 c.cm. 
 in the case of marrows of little activity — those of the fourteenth to 
 seventh day — no more than 2 c.cm. of the marrow of less than seven 
 days are given. In grave cases intervention must be prompt, there- 
 fore four injections a day are given. The first day the marrows of 
 the fourteenth and thirteenth days are employed by two punctures, 
 one in each hypochondriac region; in the evening of the same day 
 the marrows of the twelfth and eleventh days are injected. The 
 following day the marrows from the tenth to the seventh day are 
 used. On the third day of the treatment two injections are given 
 with the marrow of the sixth day. After that, one injection is given 
 daily with the more virulent marrows. When the marrow of the 
 third day is reached a new series is begun, starting with the marrow 
 of the fifth clay; then recourse is had to a third and even a fourth 
 series. At times, at the end of the treatment the patient complains 
 of pain at the point of the cicatrices ; in such cases a new vaccination 
 is undertaken according to the intensive method, and the symptoms 
 often disappear. It is thus conceivable that the vaccination must 
 not be applied in the same manner in all patients ; we cannot, however, 
 dwell upon the details of the treatment, which varies with each case, 
 and the duration of which is limited between fifteen and twenty-two 
 days. 
 
 Pasteur's method is at present employed in a great number of 
 countries; it has at times undergone more or less important modifi- 
 cations. Thus, in countries where rabbits are smaller than ours the 
 spinal marrows dry rapidly and lose their virulence more speedily. 
 It is, therefore, possible to begin the injections with marrows of the 
 tenth or eighth days, as is done by Babes in Bucharest, and Bujwid 
 in Warsaw. The latter experimenter gives the series of marrows 
 from the twelfth to the third days in four days, and repeats the same 
 series three times. In desperate cases Bardach and Gamaleia have 
 
HYUTKNK AND PROPHYLAXIS OF INFECTIOUS DISEASES. Hr,<) 
 
 employed the entire series of viruses each day for three da; 
 cession, reaching the specimen of one day. I 1 i nun''' 
 mention all the modifications of the treatment. Reference musl be 
 made to the attempt of Ferran, who did qo1 he itate to injeci non- 
 attenuated viruses. Although his method seems id have given j 
 results, it has produced disturbances in Milan at the hands of Bareggi. 
 
 It has likewise been possible, at leasl In the case of animal 
 confer immunity against hydrophobia by other procedures. I>r. 
 Galtier's experiments have already been alluded to. More recently 
 Drs. Nocard and Roux have taken up the method of intravenous 
 injections by substituting for saliva ;i more certain virus furnished 
 by an emulsion of spinal marrow. They have thus succeeded in vac- 
 cinating sheep, and even saving several into the eyes of which, 
 twenty-four hours previously, they had inoculated the virus of hydro- 
 phobia. Intravenous injection may also confer immunity upon the 
 dog, provided a weak virus be first employed, and then gradually 
 specimens of progressively growing activity (Protopopoff). More- 
 over, vaccinations have also been practised by means of diluted 
 viruses (Bardach), as well as with viruses attenuated by heal I ' 
 
 The brief history of facts above given demonstrates that the virus 
 of hydrophobia, when rendered inoffensive by one of the foregoing 
 procedures, may confer immunity. The mechanism by which this 
 effect is obtained has been a question. In view of the results ol iservei I 
 in other infectious diseases, an effort has been made to learn whether 
 antirabic vaccination does not depend upon soluble substances elab- 
 orated by the agent of hydrophobia. Prof. Bouchard attempted to 
 vaccinate by means of marrow triturated in water and filtered 
 through porcelain. The fluid thus obtained did not confer immunity 
 against inoculation later practised beneath the dura mater. This 
 negative result was confirmed by De Blasi and Travali. These 
 authors succeeded, however, in rendering animals refractory to intra- 
 venous inoculations by the same procedure. Babes and Lepp have 
 likewise conferred immunity by injecting cerebral substance sterilized 
 by heating at 176° F. (80° C). 
 
 Pasteur thought that his procedure did not attenuate the virus but 
 decreased its quantity. A rabbit into which this so-called attenu- 
 ated virus is injected succumbs in thirty days, and its medulla as 
 well as the fixed virus, when inoculated mto a second rabbit, kills 
 the latter in seven days. Desiccation is supposed to destroy the 
 virus more rapidly than the vaccine, so that the marrows rapidly lose 
 
860 INFECTIOUS DISEASES. 
 
 their noxious properties, while they preserve their vaccinating prop- 
 erties for a longer time. 
 
 The attenuation of marrow attributed by Protopopoff and Blasi 
 and Russo-Travali to the action of heat seems to depend upon a 
 phenomenon of oxidation brought about by heat. Thus, Zagari has 
 found that marrows placed in dry air remain virulent for ten days 
 at a temperature of 68° F. (20° C), and for only sixty-six hours at 
 95° F. (35° C). The virulence is more rapidly lost in hydrogen; it 
 is preserved longer in vacuo, and especially in carbonic acid. If it 
 disappears under these conditions, it is due to the fact that the 
 marrow, at the time it is taken from the body, retains a certain 
 amount of oxygen which serves the ulterior phenomena of oxidation. 
 The immunity conferred by the Pasteurian method seems to be fairly 
 durable. It persists for two years in dogs. It may be transmitted 
 even by heredity : at least this is what seems to be proved by a very 
 interesting fact published by Hogyes: of four young born from a 
 refractory couple and inoculated in the eye when three months old, 
 one died; two succumbed after a very long incubation; the fourth 
 survived and resisted two additional inoculations. 
 
 Such are the facts that may be recorded in favor of Pasteur's 
 method. They demonstrate the possibility of attenuating or rather 
 modifying the virus of hydrophobia and that this modified virus ren- 
 ders animals refractory to hydrophobia and enables bitten individ- 
 uals to resist the infection. 
 
 Immunization against Cholera, Bubonic Plague, and Typhoid Fever. 
 Haffkin indicated two procedures for vaccinating against cholera. 
 The first consists in injecting an attenuated virus, and eight days 
 later a strong virus. The second procedure is based upon the employ- 
 ment of cultures sterilized by a 0.5 per cent, solution of carbolic acid. 
 Since 1893 the anticholeric vaccine has been inoculated in India into 
 more than 100,000 individuals. The mortality is said to have been 
 diminished by about 15 to 20 per cent. However, strange to relate, 
 while cholera is less frequent among vaccinated individuals, it seems 
 to be just as grave when it attacks them. 
 
 In order to prevent bubonic plague Haffkin employed cultures of 
 the bubonic bacillus heated to 161.5° F. (72° C). The immunity 
 thus conferred lasts more than six months. Statistics seem to show 
 that the prophylactic results are quite clear. Morbidity is decreased, 
 and the mortality, which is 62 per cent, in non-vaccinated subjects, 
 falls to 27 per cent. 
 
HYGIENE AND PROPHYLAXIS OF INFECTIOUS DISEASES. H(;i 
 
 Finally, lei us mention the attempts of Wright, who vaccini 
 against typhoid fever by means of culture sterilized by heat. I 
 inoculations have been practised in Mi'' army of India, and have 
 reduced the number of cases. 
 
 Dangers of Vaccinations. A grave objection may bo made againsi 
 
 all these methods. An infection, whatever ii may be, and how< 
 benign that it may besupposedto be, gives rise to a seri turb- 
 
 ances and lesions. It produces in the organism nutritional modifi- 
 cations and changes in the constitution of the fluids, which account 
 for the immunity acquired. The morbid work may !"■ so slighl :i 
 to be unnoticeable. We cannot, however deny the reality, and 
 sequently we must, in a certain measure, fear these new methods. 
 
 Breeders assert thai sheep h unized againsi anthrax do not 
 
 develop as well as others. Hence, vaccination is practised 
 larly in Beaucc. The losses caused by ;i lew cases of anthrax are 
 less considerable than depreciation resulting from immunization. 
 Upon the author's advice, Dr. Kaplan 1 studied this question. Be 
 examined two lots of sheep, one vaccinated, the other not vaccinated. 
 By watching the animals and weighing them regularly, he found no 
 notable differences. It has also been questioned whether vaccina- 
 tions could not induce a fatal infection in a predisposed individual 
 who is already sick and suffering. What we have learned from 
 experimentation on microbic associations gives a certain importance 
 to this criticism. This objection has been raised particularly with 
 regard to antirabic treatment. Leaving aside contestable report s, il 
 must be remembered that eminent bacteriologists, like Babies, have 
 cited cases in which vaccinal hydrophobia has given rise to disorders. 
 These cases are undoubtedly exceptional; they do not impair the 
 value of the method, and must not prevent its employment against 
 bites. They must only render us more circumspect when the ques- 
 tion is one of prophylaxis. 
 
 Serum Prophylaxis. In the presence of the inconveniences result- 
 ing from the introduction into the organism of even attenuated living 
 viruses or of toxins, attempts have been made to secure prophylaxis 
 by means of serums. Preventive inoculations have been practised 
 against streptococcic infections, notably puerperal fever; against 
 bubonic plague, tetanus, and diphtheria. Heubner established that 
 injections of antidiphtheritic serum repeated every three weeks com- 
 
 1 Kaplan. Contribution a. l'etude du charbon. Son etat actuel en Beauce. These 
 de Paris, 1900. 
 
862 IXFECTIO US DISEA SES. 
 
 pletely suppressed the contagion in the hospitals. For his part, the 
 author believes that it is better to struggle against contagion by- 
 isolating suspicious cases. The author never resorts to preventive 
 injections, and for the last six years has never observed a single inter- 
 nal case. He believes, however, that this method must be employed 
 when several cases occur in an establishment or a family. In other 
 words, preventive serumtherapy must be a method of exception 
 which may render immense service in certain instances, but which 
 must not be laid down as a general rule. There will always be time 
 enough for practising injections of serum when the infection is con- 
 tracted. In order that intervention may be timely, it is necessary 
 to watch with particular care individuals who have been in contact 
 with diphtheria cases. This reservation is confirmed by the fact that 
 physicians who treat diphtheria cases are not in the habit of prac- 
 tising preventive inoculations upon themselves or their families. The 
 same rules are applicable to other serums. If an epidemic of puer- 
 peral fever should reign in a ward, it would be advisable to practise 
 prophylactic injections of serum, but we do not advise to thus inject 
 every puerperal woman. Likewise, antitetanic serum should not be 
 employed every time an individual happens to have an abrasion; but 
 it will be useful in certain regions where tetanus is endemic. Lastly, 
 the antibubonic serum, although less efficacious than Haffkin's vac- 
 cine, has the advantage of being less dangerous. It may, therefore, 
 be employed at the time of an epidemic. 
 
 Thanks to the multiple procedures which we possess at present, it 
 is possible to confer immunity against a great number of infections. 
 A more and more accurate knowledge of pathogenic agents, of their 
 distribution in nature, their mode of penetration into the organism 
 has led to various hygienic measures which have lowered both mor- 
 bidity and mortality. The isolation of contagious cases, sterilization 
 of contaminated objects, the destruction of germ-bearing organic par- 
 ticles often suffice to arrest the spread of disease. These divers 
 methods are no more than a systematization of ancient ideas. An- 
 tiquity had a certain foresight of the results obtainable by prophy- 
 laxis, as is indicated by the hygienic laws of Moses and, in the middle 
 ages, the creation of lazarettos and quarantines. What belongs to 
 the modern epoch is the formulation of precise rules based upon 
 experimental facts — substitution of scientific data for intuition. 
 
 Alongside of other hygienic measures there arises a new method of 
 prophylaxis, viz., vaccination, likewise an ancient method originated 
 
HYGIENE AND PROPHYLAXIS OF INFECTIOUS DISEASES. 
 
 in China. Et was not until about the middle of the eighteenth century 
 fchat variolization was introduced into Europe. I) wbm no1 long 
 employed. A sure and inoffensive method for this uncertain and 
 dangerous procedure was substituted by the geniue of Jenner. A 
 century later another genius, Pasteur, demonstrated thai an artifi- 
 cially modified vims could be placed by tie- ride <>(' ■■> naturally 
 inoffensive virus. A new prophylactic method thue took it- | 
 tion among the means which enabled mankind to Bghl infections. 
 Finally, the third method is thai which was developed aboul ten 
 years ago as a resull of Uehring's and EGtasato'fi laboi 
 
 Prophylaxis by hygiene — i. c, by isolation and disinfection 
 prophylaxis by Jennerian vaccination, by Pasteurian vaccination, 
 by serumtherapy — these are the great methods which science al the 
 beginning of the twentieth century places al the disposal of mankind 
 for combating epidemics, arresting their march, and lowering their 
 mortality. 
 
I N DEX. 
 
 by 
 
 , 220 
 
 scrim 
 
 injection . 
 characters of, 
 
 ABSCESS of 
 produced 
 739 
 
 Actinomyces, biologic 
 
 31 l 
 cultivat ion of, -<\ 5 
 
 Actinomycosis, 31 I 
 
 etiology of, 317 
 evolution of, 317 
 inoculations of, 316 
 Adenopat hies in smallpox, 386 
 s\ philitic and tubercular, 386 
 tracheobronchial, KIT 
 Age, influence of, upon prognosis, 632 
 Albuminuria caused by scrum injections, 
 
 742 
 Alimentary canal. See also Digestive 
 apparatus, 
 antisepsis of, 6<iS, 672 
 combined infect ions in, 1 IS 
 
 gangrene of, 241 
 
 infection by, 105 
 putrefactions in, III 
 
 suppurations of, 21 I 
 
 Alimentation, 841 
 Aliments. See also Fasting. 
 
 role of, in the transmission of in- 
 fections, 75 
 Ameba, varieties of, 41 
 Amyloid degeneration, 328 
 Anginas, treatment of, 662 
 Anthrax, intraplacental transmission of, 
 581 
 
 symptomatic, toxin of, 126 
 
 toxin of, 126 
 Antipyrin, action of, on hectic fever of 
 tuberculosis, 802 
 
 use of, at terminal period of infec- 
 tion, S03 
 Antisepsis of alimentary canal. 66S 
 
 by chemical agents. 653 
 
 general, 673 
 
 of genital and urinary organs, (iiil 
 
 of intestine, 672 
 
 of mouth, 662 
 
 by physical agents. 652 
 
 of respiratory passages, 665 
 
 of serous membranes. 671 
 
 of skin. 659 
 Antiseptics, 657 
 Antithermics, chemical, 801 
 Antitoxinie method, 675 
 Aphasia. 409 
 
 \ pparat us, circulator} . 
 and \ 1 1- M' . 
 influence ol infeel ion - upon. 1 13 
 treatment of cardiovascular mani- 
 festations, 825 
 Appcinlicit is. experimental, 215 
 \ rteries, ad ion of infeel iong upon, 153 
 Axterioscleroc is, role of infeel wmh in de- 
 velopment of, 155 
 
 Art liropal hies, infect ioUS, I Hi 
 
 produced by scrum injection-. 711 
 Aspergillu - euro! ium repens, W 
 
 Savescens, Ml 
 
 fumigatus, 10 
 
 oidulans, 10 
 
 nigricans, 40 
 Astringents, 791 
 
 Autobactercinia, 2 17 
 
 Autoinfections, 78, 92 
 
 Autointoxication-. 78 
 
 BACILLI, 37 
 classification ol 
 Bacillus, colon, toxins of, L28 
 of glanders, biology of. 37 1 
 septicus putidus. toxins of, 127 
 of tuberculosis, biology of, 277 
 Bacteria accidentally pyogenic, 190 
 action of chemical agents on, 55 
 of heat on. 53 
 of light on, 54 
 of organic fluids on, 553 
 of pressure on, 50 
 of serum on morphology i 557 
 anaerobic pyogenic. 189 
 classification of. 37 
 curved, 37 
 determination of. 43 
 distribution of, within normal or- 
 ganism. 7'.» 
 general characters ■ 
 importance of number of, in the de- 
 velopment of infection-. 98 
 influence of various external agents 
 
 upon. 50 
 mode of action of, 10S 
 modes of entrance of, 101 
 non-specific, classification of, ^ v 
 parasitic. 35 
 passage o\. from a saprophytic to a 
 
 pathogenic life, 36 
 pathogenic. 35 r 
 
 55 
 
866 
 
 INDEX. 
 
 Bacteria, polymorphism of. 43 
 
 pyogenic, 1S5 
 
 relation of, to algse, 35 
 
 role of, in development of infections, 
 
 98 
 
 saprophytic, 35 
 
 search tor pathogenic, by micro- 
 scopic examination and cultiva- 
 tion, 607 
 selective injuriousness of, 100 
 specific, classification of, 39 
 
 pyogenic, 190 
 toxins of, 120 
 variability of functions of, 46 
 
 of pathogenic properties of, 49 
 variations in virulence of, 99 
 Bacterial ferments, 47 
 
 pigments, variability of, 47 
 Bacteriology, determinism in, 61 
 of gaseous gangrene, 232 
 of septicemia, 248, 258 
 Bacteriotherapy, 681 
 Balneotherapv. See Baths. 
 Baths, cold, 793 
 
 lukewarm, 793 
 Bicarbonate of soda, influence of, on pro- 
 tective action of liver, 161 
 Blood, action of venous, upon tempera- 
 ture, 350 
 bacterioscopic examination of, 367 
 microscopic study of, 363 
 modifications in, catised by serum 
 injections, 745 
 of, in course of infections, 359 
 protective role of, 761 
 role of, in thermal regulations, 348 
 toxicity of, in some infections, 132 
 Blood-letting, 805 
 Bone-marrow, in infections, 369 
 lesions of, in infections, 376 
 modifications of, in experimental in- 
 fections, 370 
 normal anatomy and phvsiology of, 
 
 369 
 reactions of, in man, 373 
 semeiology of, 377 
 Bones, infections in, 440 
 Bronchi, 457 
 Bronchitis, 457 
 
 varieties of, 457 
 Bubonic plague, immunity against, 860 
 
 serumtherapy of, 707 
 Buccopharyngeal manifestations in scar- 
 latina, 471 
 in smallpox, 472 
 suppuration, 213 
 Bulbar manifestations, 411 
 
 CALCIUM chloride. See Chloride of 
 calcium. 
 Calomel, 771 
 
 Cancer, inoculations of, 321 
 Cardiovascular manifestations, treat- 
 ment of, 825 
 
 Caustics, 790 
 
 Cells, degenerations of, 324-3.T2 
 
 Cephalalgia, 405 
 
 in infections, 405 
 Cerebral manifestations in infections, 404 
 Chloride of calcium, 787 
 Cholera, crisis in, 526 
 
 immunity against, 860 
 
 serumtherapy of, 700 
 
 toxin of, 125 
 Choleriform enteritis, 477 
 Chorea, 425 
 
 crisis in, 526 
 
 serumtherapy of, 700 
 Cinchona, 677 
 
 Circulator}' apparatus. Sec also Heart 
 and Arteries, 
 influence of infections on, 443 
 treatment of cardiovascular 
 manifestations, 825 
 
 disorders, role of, in gangrene, 230 
 Clothing, role of, in transmission of in- 
 fections, 74 
 Cocci, 37 
 Colon bacillosis, 188 
 
 serumtherapv of, 702 
 toxins of, 128 
 Coma, 408 
 
 Contagion, definition of, IS 
 Convalescence, 527 
 
 hygiene of, 844 
 Convulsions, 410 
 Crises in cholera, 526 
 
 in chorea, 526 
 
 definition of, 518 
 
 in erysipelas, 524 
 
 in pneumonia, 521 
 
 in scarlatina, 525 
 
 in typhus, 524 
 
 in various infections, 525 
 Cultivation, search for pathogenic agents 
 
 by, 607 
 Cytologic examination, 617 
 
 dis- 
 
 DEATH, 535 
 Declaration of contagious 
 eases, 845 
 Degeneration or degenerations, amyloid, 
 328 
 causes of, 326 
 cellular, 324-332 
 fatty, 327 
 pigmentary, 331 
 varieties of, 324-32(1 
 Delirium, 406 
 
 Determinism in bacteriology, 61 
 Diagnosis according to chemical modifi- 
 cations in fluids, 623 
 of infectious diseases, 606-631 
 inoculation from the point of view 
 
 of, 613 
 by microbic toxins, 624 
 rules of clinical, 627 
 by therapeutics, 624 
 
INDEX 
 
 867 
 
 Diagnosis, vesicatory test in, 81S 
 
 Digestive apparatus, flee all o Alimenl - 
 ary canal and Stomach, 
 infections in, 169 
 influence <>r infections on, 169 
 treatment of disorders of, 831 
 
 Diphtheria, serumtherapy of, 703 
 
 Diphtheritic paralysis, l~o 
 
 Diseases, infectious, flee infection . 
 
 Dysenteriform enteritis, 177 
 
 l )ysentery, amebic, 176 
 bacterial, 476 
 
 Dystrophies, of infectious origin, 598 
 
 EAK, auricular suppural ions, 21 I 
 Embolism, 335 
 
 Emunctories, protect ive r. >l< • of, 702 
 Endocarditis, 449 
 
 Undomyces :illiic:i.!is, \W.\ 
 
 Ententes, choleriform, 177 
 
 dysenteriform, 177 
 Epidemics, 67 
 
 influence of, upon prognosis, 633 
 variations of, with countries and 
 epochs, 96 
 Epilepsy, -425 
 Ergot, 789 
 Ergo tin, 771 
 
 Eruption, relationship between intensity 
 of eruption and gravity of disease, 434 
 Eruptive fevers, serumtherapy of, 730 
 
 transmission of, f>S<> 
 Erysipelas, crisis in, 524 
 
 treatment of, by lukewarm baths, 
 S00 
 Erysipelatous paralysis, 422 
 Erythemata, mechanism and variability 
 
 of infectious, 439 
 Etiological conditions, importance of, in 
 
 diagnosis, 634 
 Etiology of infections, 64-97 
 Examination, cytologic, 617 
 
 microscopic, search for pathogenic 
 agents by, 607 
 Exanthemata, 431 
 
 produced by serum injections, 739 
 Experimentation, role of, in study of in- 
 fectious diseases, 58 
 Exudates, serous, 174 
 Eye, ocular suppurations, 214 
 
 FAMILY, role of, in infections, 86 
 Farcina bovidse, 39 
 Fasting, influence of, upon protective 
 
 action of liver, 160 
 Fatigue, influence of, on infections, 94 
 Fatty degeneration, 327 
 Febrile manifestations, treatment of, S19 
 Fecal matters, toxicity of, 116 
 Ferments, bacterial, 47 
 Fetid pleurisy, 240 
 Fever or fevers, 33S 
 
 caused by injection of serums, 741 
 
 I • •!, chara< U i 
 
 Seal ion o 
 
 deflnil loi 
 
 eruptive, erumthcrap ■ 
 
 mechani m ol , 3 W 
 
 i .,i' of blood i' 
 
 ■ meiological \ .• 1 1 1 1 « ■ of, 
 
 i berap ul ic of, 7!»2 
 
 typhoid, auto 
 
 clinical form of, 516 
 coni vindications of cold 
 i 1 1 tr in, < 
 
 1 1 1 1 1 r 1 1 1 1 1 1 1 
 
 erumthei 729 
 
 to in of, 131 
 Fluids, organic, flee also Blood and 
 
 iin. 
 .ici ion of, on bacteria, G 
 modifical ions in, •''.•'>7 
 various, employed in thi i 
 tics, 697 
 Food. Sec also Alinnni -. 
 
 role of, in the transmission of infec- 
 tions, 7.", 
 Fungi, infectious, 39 
 
 GALLING, tuberculosis of, 290 
 Gangrene, 225-243 
 Gangrene, causes favoring development 
 
 * of, 227 
 definition of, 227 
 gaseous, bacteriology of, 232 
 toxin of, 126 
 various agents of, 2:w 
 of limbs, 235 
 of liver, 241 
 of lungs, 238 
 of mammary glands, 235 
 principal agents of, 232 
 pulmonary, 238 
 role of chemical agents in, 230 
 
 of circulatory disorders in, 230 
 
 of intoxications in, 231 
 
 of mechanical and phvsical 
 
 agents in, 229 
 of nervous system in, 231 
 of spleen, 241 
 treatment of, 781 
 in various parts of organism. 235 
 Gangrenous lesions, treatment of, 781 
 
 pleurisy, 240 
 Gastrointestinal putrefactions, 114-120 
 Generation, spontaneous, 34 
 Genital organs, antisepsis of, 661 
 Genito-urinarv organs, antisepsis of, 661 
 gangrene of. 241 
 infection by, 106 
 influence of infections on, 490 
 suppurations of, 221 
 Germicidal substances, role of spleen in 
 
 production of. 3S1 
 Glanders, animals sensitive or refraetory 
 to, 275 
 
868 
 
 IXBEX. 
 
 Glanders, bacillus of, biology of, 374 
 
 etiology of, 275 
 
 pathological anatomy of, 276 
 
 serum therapy of, 709 
 
 toxins of, 131 
 Glucose, influence of, upon protective 
 
 action of liver, 160 
 Guaiacol, 804 
 
 HEART. See also Myocarditis, En- 
 docarditis, and Pericarditis. 
 
 action of toxins upon, 444 
 
 functional disorders of, 443 
 
 post-infectious hypertrophy of, 448 
 Hemiplegia, 409 
 
 Hemorrhages, caused by injections of 
 serum, 744 
 
 causes of, general, 785 
 local, 783 
 
 therapeutic indications of, 780 
 
 treatment of, 783 
 Hemorrhagic pleurisy, 467 
 
 septicemia, 245, 255 
 Heredity, 580-605 
 Heterointoxications, 64 
 
 of gastrointestinal origin, 118 
 Humoral modifications of lymphatic 
 
 origin, 387 
 Hydrocele, 776 
 Hydrophobia, serumtherapy of, 735 
 
 vaccination against, 855 
 Hygiene of convalescence, 844 
 
 individual, 837 
 
 of sick, 840 
 
 of sick room, 837 
 
 social, 845 
 Hyperthermia, 33S 
 
 IMMUNITY, acquired, 559 
 congenital, 599 
 individual, 88 
 mechanism of, 551-579 
 natural, 557 
 Immunization against cholera, typhoid 
 fever, and bubonic plague, 860 
 by attenuated viruses, 854 
 by means of strong viruses, 847 
 Incubation, 495 
 
 importance of duration of, in prog- 
 nosis, 635 
 period of, 22 
 Infantile paralysis, 417 
 Infection or infections, abortive, 512 
 action of, on organs of sense, 428 
 of poisons upon, 91 
 of, on respiratory apparatus, 
 456 
 autogenic origin of various specific, 
 
 81 
 bones in, 440 
 cephalalgia in, 405 
 circulatory apparatus in, 443 
 classification of, 24 
 
 Infection, clinical forms of, 511 
 combined, 142 
 
 in alimentary canal, 148 
 
 in respiratory apparatus, 147 
 
 of skin, 145 
 
 of throat, 145 
 consequences of, 541-550 
 cutaneous manifestations in, 429 
 
 origin, 102 
 declaration of, 8 15 
 definition of, 24 
 
 diagnosis and prognosis of, 600-641 
 digestive apparatus in, 469 
 eruptive, 26 
 etiology of, 64-97 
 evolution of, 494-540 
 history of, 30 
 
 hygiene and prophylaxis of, 537-863 
 incubation of, 495 
 individual immunity from, SS 
 
 predisposition to, 88 
 influence of' age on, 88 
 
 of autoinfections on, 92 
 
 of family on, 86 
 
 of fatigue and overwork on, 94 
 
 on genital organs, 490 
 
 of individuals on, 88 
 
 on neuropathies, 427 
 
 of poisons on, 91 
 
 of seasons on, 84 
 
 of sex and age on frequency 
 of, 89 
 intraplacental transmission of 
 chronic, 593 
 
 of human, 583 
 invasion of, 503 
 lesions of bone-marrow in, 376 
 lymphatic glands in, 382 
 meaning of, 17 
 miasmatic, 18 
 
 modifications of blood in course of, 
 359 
 
 bone-marrow in experimental, 
 370 
 muscular system in, 438 
 nervous system in, 403 
 neuroses following, 423 
 non-specific, 29 
 
 passage of acute to a chronic condi- 
 tion, 531 
 pathogenesis of, 98-134 
 role of, in development of arterio- 
 sclerosis, 455 
 
 of, in development of general 
 paralysis, 408 
 secondary, 144 
 
 simultaneous occurrence of two, 143 
 specific, 25, 29 
 spinal cord in, 412 
 spleen in, 378 
 stationary period of, 506 
 suprarenal capsules in, 400 
 termination of, 516 
 therapeutics of, 642-836 
 through alimentary canal, 105 
 
INDEX 
 
 
 Infection through genito urinarj organs, 
 
 100 
 
 nervous system, L06 
 organs of sense, 1 06 
 respiratory pa sages. 103 
 .serous membrane i, 106 
 \ ascular system, 1 07 
 thymus in, 387 
 thyroid gland in, 393 
 i ransmission of. by contact, 65 
 through aliments, 75 
 air, 69 
 (•In! hin^, 7 I 
 invertebrates, !'■'< 
 plants, 7 I 
 
 by soil, 72 
 
 by water, 71 
 tumors and, :il !> 
 venereal, 27 
 virulent, 31 
 
 with nodular productions, 2.x 
 with septicemic tendency, 27 
 Infectious agents, action of, ~\ 
 classifical ion of, 35 
 mode of en1 ranee of, 101 
 Inflammatory exudates, treatment of, 
 772 
 manifestations, treatment of, 765 
 Infusoria, :! I 
 
 Inoculation or inoculations. Sec, also 
 Vaccination. 
 of actinomyces, 316 
 of cancer, 321 
 
 from a diagnostic standpoint, 013 
 
 subcutaneous, 102 
 
 of tuberculosis, 288 
 
 Insanity in tuberculosis, 407 
 
 Intestine, antisepsis of, 072 
 
 choleriform and dysenteriform affec- 
 tions of, 177 
 disturbances and lesions of, in in- 
 fections, 474 
 Intoxications, role of, in gangrene, 231 
 Intraplacental transmission of anthrax, 
 581 
 of chronic infections, 593 
 of human infections, 5S3 
 Invasion, 503 
 
 importance of mode of, in diagnosis, 
 635 
 Invertebrates, role of, in transmission of 
 
 infections, 73 
 Iodine, 67S 
 Ipecac, 790 
 
 I, .pro ■ 1 1 1 1 > 1 1 1,. ■i:i|,- .,| 70'i 
 
 Leptotnrix, 37 
 I., ion or li 
 
 local, role of, in uppir 
 
 108 
 reparat ion ol • raumal ic and a 
 
 infect iou . 5 1 1 ■"• 15 
 uppurat ing, generalizat ion i 
 Leucoi U ■• 364 
 
 Limb 
 
 Liver, aoHct i • ■ 220 
 act ion "i . on micro 
 gangrene of, 211 
 general charactei ol in 1 
 influence ol bicarbonate ol raids, on 
 protect ive act ion ol . 161 
 >.i fasting upon protect 
 
 lion of, 160 
 of glucose upon protect 
 
 1 ion ol . 160 
 of infect iouf di -•■■' • 
 protect i\ e rdle of, l"> r >. 1 59 ■ 
 role of, iii 1 hermogenesis, 351 
 semeiology of infection-. ts7 
 Lungs. See also Respirator apparatus, 
 classification of lesions of, of infec- 
 tious origin, 160 
 gangrene of, 238 
 in infect ioua diseases, i". n 
 
 normal physiology of, 158 
 protect i\ e role of, 1 56, 760 
 
 role of, in thermogenesis, 351 
 Lymphatic glands, histological stud 
 384 
 
 in infect ions, 382 
 inflammation of, in variola. 386 
 protective rdle of, 1">1 
 
 of, 
 
 K 
 
 IDNEYS, influence of infectious on, 
 
 4S9 
 role of, in thermogenesis, 351 
 
 treatment of renal disorders, 835 
 
 T ACTATION, influence of infections 
 
 on, 491 
 Larynx in infections, 456 
 
 MALLEIX, 625, 694 
 Mammary glands, gangrene 
 
 235 
 
 Measles, buccopharyngeal manifestations 
 in, 470 
 
 Medication, depletive. ,71 
 
 physiological, 757 
 
 specific. 676 
 
 symptomatic, S19 
 
 vasomotor, 771 
 Meningitis, infectious, 426 
 Menstruation, influence of infections 
 
 490 
 Mercury. 07s 
 Meteorological influence on infect 
 
 84 
 Miasmatic diseases, L8 
 Microbes. See also Bacteria. 
 
 association of, 135-153 
 
 modifications of action of liver upon. 
 159 
 
 necrosing role of pyogenic. 234 
 
 passage of, through placenta. 580 
 
 toxins of pyogenic. 129 
 Microbie associations. 135-153. 10<> 
 
 products, favorable to infection. 137 
 
870 
 
 fXDEX. 
 
 Milk, passage of active substances into, 
 568 
 role of, in the transmission of infec- 
 tions, 75 
 Mouth, antisepsis of, 602 
 
 buccopharyngeal manifestations in 
 measles, 470 
 in scarlatina, 471 
 in varicella, 472 
 in variola, 472 
 in various infections, 472 
 Murmurs, non-organic, of heart, 443 
 Muscles or muscular system in infections, 
 
 43S 
 Mycoses in man, 319 
 Myelitis, 414 
 
 in various infections, 417 
 Myocarditis, acute, 446 
 
 "VTEPHRITIS caused by serum injec- 
 1M tions, 742 
 Nervous connections, 337 
 
 manifestations, treatment of, 821 
 system, connections of, 337 
 infection through, 106 
 in infections, 403 
 role of, in development of gan- 
 grene, 231 
 nervous alterations in sup- 
 puration, 197 
 suppuration of, 222 
 treatment of manifestations of, 
 821 
 Neurites, 419 
 Neuropathies, influence of infections on, 
 
 427 
 Neuroses following infections, 423 
 
 post-infectious, 423 
 Nocardia farcinosa, 39 
 Nodular infections, 272-322 
 
 lesions, treatment of, 783 
 Nose, nasal suppurations, 213 
 
 OBNUBILATION, 408 
 Oidiomycosis. See also Endomy- 
 cosis. 
 biology of parasite of, 302 
 experimental, 307 
 histological study of, 309 
 nature of, 312 
 Oidium albicans, 302 
 
 characters of cultures of, 304 
 role of, in human pathologv, 
 304 
 Omentum, protective role of, 154 
 Oomyces, 40 
 Oospora asteroides, 39 
 Organism, defenses of, 154, 181 
 
 influence of infections on, 359-493 
 reactions of, against infections, 166 
 
 inflammatory, 168 
 return of, to a former state of its 
 evolution, 549 
 
 Organism, suppuration in various parts 
 
 of, 212 
 Organs. See also Tissues and Cells. 
 
 action of various, upon microbic 
 
 poisons, 164 
 contiguity of, 334 
 
 modifications of hematopoietic, 368 
 of sense, action of infections on, 428 
 infection by, 106 
 Osteopathies, infectious, 440 
 Overwork, influence of, upon infections, 
 94 
 
 PANCREAS, action of infections on, 
 488 
 suppurations of, 221 
 Paralysis or paralyses, acute ascending, 
 ' 414 
 
 diphtheritic, 420 
 erj'sipelatous, 422 
 
 general, role of infections in develop- 
 ment of, 408 
 infantile, 417 
 scarlatinal, 422 
 Parasites capable of inducing suppura- 
 tion, 183 
 pyogenic, animal, 192 
 
 relative frequency of, 193 
 vegetable, 191 
 Parasitic agents, action of, 23 
 Parrots, tuberculosis of, 293 
 Pathogenesis of infections, 98-134 
 Pathogenic agents, mode of action of, 
 108 
 of entrance of, 101 
 search for bj r microscopic ex- 
 amination and cultivation, 
 607 
 selective injuriousness of, 100 
 Pericarditis, 452 
 Peritonitis, tubercular, 775 
 Peroxide of hydrogen in treatment of 
 gangrene, 781 
 of hemorrhages, 792 
 Perspiration, 437 
 Phycomyces, 40 
 Pigmentary degeneration, 331 
 Pigments, bacterial, variability of, 47 
 Placenta, intraplacental transmission of 
 chronic infections, 593 
 passage of microbes through, 580 
 Plants, role of, in transmission of infec- 
 tions, 74 
 Plasmodium malaria?, 42 
 Pleura, lesions of, in infections, 465 
 Pleurisy or pleurisies, gangrenous and 
 fetid, 240 
 hemorrhagic, 467 
 purulent, 467 
 serous, 465 
 treatment of, 772 
 Pneumococcosis, serumtherapy of, 710 
 Pneumococcus, 187 
 toxin of, 130 
 
INDEX. 
 
 871 
 
 Pneumonia, clinical forma of, 515 
 
 crisi.s in, . r >2l 
 
 Poisons. See also Ptomainsand Toxins, 
 action of, on infections, 91 
 liver on, I 62 
 of various organs on microbio, 
 
 Kil 
 
 defenses of organism against) 162 
 found in infected organism i, 1 8 1 
 tnicrobic, 10!' 
 ptomain, 1 13 
 putrid, L09 
 Predisposition. 88, 551 679 
 
 congenital, 599 
 Pregnancy, influence of infections on, 
 
 mi 
 Prognosis, bases of, at stationary period, 
 635 
 general rules of, <>:{!) 
 importance <>i duration of incuba- 
 tion and of mode of invasion in, 
 i>;?. r ) 
 of infectious diseases, 631 
 influence of age on, 632 
 of epidemics on, 633 
 of se\ on, <>:w 
 
 of serumtherapy accidents, 717 
 
 Prophylaxis by serum, 861 
 Proteobacillosis, serumtherapy of, 712 
 
 Protozoa, infectious, 41 
 Pseudomembranes, 176 
 
 diphtheritic, 177 
 I Veiidomcmbranous exudates, treatment 
 
 of, 781 
 1 'seudotuberculosis, 295 
 
 by animal parasites, bacterial, 29S 
 human, 301 
 micotic, 297 
 
 by inanimate substances, 295 
 Ptomains. Sec also Poisons and Toxins. 
 
 table of, 113 
 Pulmonary gangrene, 238 
 Purulent exudates, treatment of, 777 
 
 foci, development and evolution of, 
 20S 
 
 pleurisy, 467 
 Pus. See also Suppuration and Puru- 
 lent Foci. 
 
 physical and chemical characters of, 
 204 
 Putrefactions, gastrointestinal, 114-120 
 Pyemia. See also Septicemia. 
 
 of animals, 255 
 
 attenuated form of, 264 
 
 clinical evolutions of, 261 
 
 distinction of, from septicemia, 244 
 
 experimental, 250 
 
 history of, 251 
 
 human, 257 
 
 relationship between variola and, 
 265 
 
 relative frequency of agents of, 260 
 
 of saprophytic origin, 254 
 Pyocyanobacillosis, serumtherapy of. 712 
 Pvramidon. S03 
 
 / |HMM 
 
 RABBI] -. epizootic purulent rhinitis 
 of, 256 
 < cperimental \ ariola ol 
 [label's water, 786 
 Rabie , .-< ■ n drophobia. 
 
 n'.le of, in infei 
 Eleactions, general, 333 
 Recurrences, 630 
 Relapses, 52!) 
 
 Renal di ordi r , I reatmenl of, 
 Re piratorj apparat u Bet ■• •■ ] >ungs. 
 action of infection! on, 156 
 ant i ep i of, 665 
 combmed infection* in, I 17 
 
 ill hi. I' r of, WO 
 
 remote consequence* of infec- 
 
 i w e lesiom ol . 168 
 nippural ion of, 214 
 manifestal ions in, 827 
 passages, antisepsis of, 665 
 infections through, 103 
 Rhatania, 791 
 
 QALICYLIC acid, 680 
 O Scarlatina, buccopharyngeal mani- 
 festations in, 1-1 
 crisis in, 525 
 Scarlatinal paralysis, 422 
 Season, influence of, in infect inns. 84 
 Secretions, passage ol activi - ibst n 
 into, 568 
 sudoral, 437 
 Septicemias of animals, 255 
 attenuated forms of, 2f>l 
 bacteriology of, 248 
 classification of, 246 
 clinical evolution of, 261 
 definition of. 244 
 experimental, 250 
 hemorrhagic, 245. 255 
 history of, 251 
 human, 257 
 
 bacteriology of. 258 
 of intestinal origin. 254 
 of nasal origin. 253 
 principal agents of spontaneous, 
 
 249 
 relationship between variola and, 
 
 265 
 relative frequency of agents 
 of salivary origin. 253 
 of saprophytic origin, 254 
 secondary, 149 
 
 localizations of, 151 
 Serous exudates, treatment of, 772 
 membranes. See also Omentum. 
 antisepsis of, 671 
 infection through. 106 
 suppurations of, 222 
 pleurisy, 465 
 
872 
 
 INDEX. 
 
 Serum or serums. See also Serum- 
 therapy. 
 accidents ascribable to injections of, 
 
 739, 746 
 action of, on morphology of mi- 
 crobes, 557, 500 
 of, on virulence, 557 
 agglutinating power of, 501 
 antitoxic properties of, 50-4 
 artificial, injections of, SOS 
 
 indications for, S14 
 attenuating power of, 562 
 mode of action of therapeutic, 751 
 modification of, in acute diseases, 
 574 
 of, in animals predisposed to 
 infections, 572 
 nature and origin of various active 
 
 substances contained in, 577 
 prophylactic injections of, 737 
 prophylaxis, 801 
 Serumtherapy, 094 
 
 accidents ascribable to, 739 
 
 of bubonic plague, 709 
 
 causes and mechanism of accidents 
 
 of, 749 
 of cholera, 700 
 of chorea, 700 
 of colon bacillosis, 702 
 of diphtheria, 703 
 of eruptive fevers, 730 
 of glanders, 709 
 of hydrophobia, 735 
 of infections whose agents are not 
 
 well known, 730 
 of leprosy, 709 
 mode of action of, 751 
 of pneumococcosis, 710 
 of proteobacillosis, 712 
 of pyocyanobacillosis, 712 
 of smallpox, 733 
 of staphylococcosis, 713 
 of streptococcosis, 714 
 of svphilis, 730 
 of tetanus, 722 
 of tuberculosis, 724 
 of typhoid fever, 729 
 of vaccinia and variola, 133 
 various applications of, 700 
 Sex, influence of, upon prognosis, 033 
 
 role of, in infectious diseases, 88 
 Silkworm disease, 34 
 Skin, antisepsis of, 059 
 
 combined infections of, 145 
 consequences of cutaneous infec- 
 tions, 436 
 cutaneous manifestations in infec- 
 tions, 429 
 suppurations, 213 
 Smallpox, adenopathies in, 386 
 
 buccopharyngeal manifestations in, 
 
 472 
 congenital, 586 
 cultivation of microbe of, 269 
 epidemiology of, 67 
 
 Smallpox, microbiology of, 267 
 
 relation of, to septicemia and pye- 
 mia, 265 
 
 serumtherapy of, 733 
 Specific medication or treatment, 670 
 Spinal cord in infections, 412 
 Spleen, gangrene of, 241 
 
 in infectious diseases, 378 
 
 role of, in production of germicidal 
 substances, 3S1 
 Sporozoa, 41 
 
 Staphylococcosis, serumtherapy of, 713 
 Staphylococcus, 185 
 Stationary period, 500 
 
 bases of prognosis at, 035 
 Sterilization of morbid products, S39 
 Stomach, action of infections on, 473 
 Stomatitis, treatment of, 002 
 Streptococcosis, serumtherapy of, 714 
 Streptococcus, ISO 
 Streptothrix, pathogenic, 318 
 Suckling by infected women, 492 
 Sudoral secretions, 437 
 Suette picarde, 90 
 
 Suppuration, 182-224. See also Pus 
 and Purulent Foci. 
 
 auxiliary causes of, 195 
 
 buccopharyngeal, 213 
 
 cold, 212 
 
 of nervous system, 222 
 
 non-microbic, 201 
 
 in clinical observations, 203 
 
 parasites of, 184 
 
 of respiratory apparatus, 214 
 
 role of general state in suppurative 
 processes, 199 
 of microbic products in, 203 
 
 in various parts of organism, 212 
 Suprarenal capsule, infections in, 400 
 Sweat, 437 
 
 Sympathies, morbid, 333 
 Symptomatic anthrax, toxin of, 120 
 Synergies, functional, 333 
 Syphilis, adenopathies in, 380 
 
 serumtherapy of, 730 
 
 TANNIN, 791 
 Tartar emetic, 771 
 Temperature, action of microbic toxins 
 on, 341 
 daily course of rectal, under normal 
 
 conditions, 350 
 semeiological value of course of, 358 
 Termination of infections, 510 
 Tetanus, serumtherapy of, 722 
 
 toxin of, 124 
 Tetany, 425 
 
 Tetracoccus buccalis, 44 
 Therapeutics, antiseptic method of, 052 
 antitoxinic method of, 075 
 bacteriotherapic method of, 081 
 diagnosis by, 024 
 of fever, 792 
 general rules of, in infections, 048 
 
in in:. \. 
 
 873 
 
 Therapeutics of infectious dises e i, ( >I2 
 836 
 physiological, 7. r >x 
 serumtherapic mel hod of. 69 1 
 specific medication in, 070 
 various organic Quids employed in, 
 697 
 Thermogenesis, rdle of kidneys in, 351 
 of li \<i- in, 361 
 oi Lungs in, 361 
 Thoracentesis, 772 
 
 rules of, 7715 
 Throat, com! lined infecl ions i if, I 16 
 Thymus, histological modification 
 in infections, 390 
 in infections, 387 
 primary infection of, 393 
 Thyroid glands, experimental tumors of, 
 320 
 general characters of, in acute 
 
 infecl ions, 396 
 in infecl ions diseases, 393 
 mechanism and significance ol 
 
 lesions of, 398 
 
 normal histology of, 39 I 
 Tissues. See also ( Irgans. 
 
 germicidal properties of, 509 
 
 Toxicity of fecal nial lers, 1 1(> 
 
 Toxins, action of microbic, upon tem- 
 perature, 341 
 of, upon organism, 1 22 
 of tubercular, 287 
 of cholera, 125 
 description of principal, 12:; 
 diagnosis by microbic, 624 
 of gaseous gangrene, L26 
 of glanders, 131 
 modes of elimination of, 164 
 of pathogenic microbes, 120 
 of symptomatic anthrax, 120 
 of tetanus, 124 
 
 of tuberculosis, actions of, 287 
 of typhoid fever, 131 
 Trachea, 457 
 
 Tracheobronchial adenopathies, 407 
 Transmission of eruptive fevers, 580 
 intraplacental, of anthrax, 581 
 of tuberculosis by contact, 08 
 by inhalation, 70 
 Treatment. See also Medication and 
 Therapeutics. 
 of anginas, 002 
 
 antiseptic, of stomatites and an- 
 ginas, 662 
 of cardiovascular manifestations, 
 
 825 
 by cold applications, 790 
 b> r depletion, 708 
 of digestive disorders, 831 
 of disorders of digestive apparatus, 
 
 831 
 of erysipelas, 800 
 of febrile manifestations, 819 
 of gangrene, 7S1 
 
 peroxide of hydrogen in, 7S1 
 
 [Veal 1 1 i'ii i oi hen 
 
 peroxidi ■ 
 li- hot applical ion 
 by immobilizat ioi 
 '.i inflammatoi •. i udate i, 772 
 
 manife tal ion 
 b) injection ol artifi( 
 
 SOS 
 
 local, 766 
 
 oi nen ou mai 
 
 oi Qodulai li 
 
 of pleuri \ -, 772 
 
 ni pseuaomembrai 
 
 7S 
 ni purulenl exudate 
 l,v refrigeral ion, 766 
 
 OI renal di ord< i 
 of respiratory man i 
 by re, ni inii. 768 
 
 oi Berous exudate . 772 
 
 of stomal il is, 662 
 
 by t horacentesis, 77:; 
 
 by \ enesection, 806 
 Drichinosis, 42 
 Tubercle, evolul ion of, 286 
 
 histo . 283 
 
 histological study of oidian, 3 
 Tubercular adenopal hies, 386 
 
 insanity, 107 
 
 peritonitis, 775 
 Tuberculin. 688 
 Tuberculosis. See also rubercle. 
 
 of animals, 289 
 
 bacillus of, biology ol . 277 
 
 el iology of, 27 ( .i 
 
 of gallina. 290 
 
 inOculabihty of, 2vs 
 
 insanity in, 407 
 
 pathological anatomy oi . 280 
 
 pseudo-, 295 
 of psittaci, 293 
 serumtherapy of, 72 1 
 toxins of. action of, 287 
 transmission of, by contact, 08 
 
 by inhalation. 70 
 vesicatory test in diagnosis of. 
 621 
 Tumors and infections. 319 
 
 experimental, of thyroid gland. 
 320 
 Typhoid fever, autogenic. v 2 
 clinical forms of. 510 
 contraindications of cold bath- 
 ing in, 795 
 immunity against, S 
 serumtherapy of, ~- 
 toxin of. 131 
 Typhus, crisis in. .V24 
 
 URINARY organs, antisepsis oi. 661 
 Urine, modifications oi. produced 
 by serum injections. 742 
 toxicity of, in some infections. 
 132 " 
 
874 
 
 IXBEX. 
 
 VACCINIA, serumtherapy of, 733 
 Vaccination against hydrophobia, 
 855 
 the oidium, 309 
 of animals, 696 
 antivariolar, 849 
 dangers of, 861 
 prophylactic, S46 
 Varicella, buccopharyngeal manifesta- 
 tions in, 472 - 
 Variola. See Smallpox. 
 
 buccopharyngeal manifestations in, 
 
 472 
 relationship between pyemia and, 
 265 
 septicemia and, 265 
 
 Variola, serumtherapy of, 733 
 Vascular connections, 335 
 
 system, infections through, 107 
 Venesection, 805 
 Vesicatory test, 618 
 Virulence, action of serum upon, 557 
 
 variations of, 99 
 Visceropathies, post-infectious, 545 
 
 role of previous, in prognosis, 638 
 
 "VTEASTS, pathogenic role of, 313 
 
 z 
 
 YGOMYCES, 40 
 
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