By .Dr. H. Bourges, 1111 LIBRARY OF CONGRESS. KC \2>tt ©|np 0qtijw$t $0 UNITED STATES OF AMERICA. SPECIAL NOTE. It was originally designed to publish this book in the ■series of 1S93, and the covers were so dated. But as the manuscript was not received early enough for publication in that series, the volume appears in the Leisure Library for 1894: hence the discrepancy between the dates on cover and title page. A TREATISE ON DIPHTHERIA. i DR. H. BOURGES. Translated by E. P. Hurd, M.D., Member of the Massachusetts Medical Society; Medical Examiner for the Third Essex District, Massachusetts ; Member of the Climato- logical Society ; one of the Physicians to the Ne-wbury- port Hospital; Professor of Pathology in the College of Physicians and Surgeons, Boston, Massachusetts. mi - r,.^-i*h-r~ GEORGE S. DAVIS, DETROIT, MICH. IIP Copyrighted by GEORGE S. DAVIS. TABLE OF CONTENTS. Page Translator's Preface i-xxii Author's Preface i- 2 Diphtheria — History 3- 10 Etiology and Bacteriology n- 37 The Diphtheria Poison 38- 48 Secondary Infections in Diphtheria 49- 50 The Pseudo-Diphtheritic Bacillus 51-55 False Diphtherias 56- 57 Animal Diphtheria 58-63 Symptoms: Of Bacillary Infection; of Systemic Poisoning 64- 89 Complications Due to Secondary Infections 90- 94 Clinical Forms 95-103 Diphtheria in Adults 104-105 Secondary Diphtherias 106-107 Progress. Duration, Termination 108-111 Prognosis 112-114 Diagnosis 115-119 False Diphtherias 120-125 Pathological Anatomy 126-131 Lesions Produced by the Diphtheria Poison 132-143 Lesions Due to Secondary Affections 144-145 Treatment: Local; General; Treatment of Certain Signs of Intoxication; Treatment of Secondary Infections; Hygiene of Convalescence 149-167 TRANSLATOR'S PREFACE. Probably no disease is the subject of more general interest to physicians than diphtheria, as none is a more favorite topic of discussion at medical meetings. Recent bacteriological researches have wonderfully- advanced our knowledge of its etiology, while the therapeutics of diphtheria have hardly kept pace with this progress. The remedies proposed are legion, but all too poorly fulfill their end, and the mortality from this disease still remains very high. We are still without a specific, though the profession is looking for one; but physicians are learning more intelligently to combat diphtheria, and the gains which prophylaxis has made are great. Under the head of the nature of diphtheria, there are two points to consider: first, the question of its microbial origin; second, whether it is primarily a local or a general disease. i. Till within a few years, nothing definite has been known about the contagion of diphtheria. There is now a growing disposition to accept as substantiated the claims alleged in behalf of the Klebs-Loeffier ba- cillus, especially in view of the recent confirmation of these claims by Roux and Yersin, of Paris, also by Drs. Abbot and Welch, of Baltimore. This bacillus is about as long and twice as thick as the tubercle bacillus; its extremities are rounded; it is immovable; it forms groups of chains, each element of which be- comes club-shaped at its extremity. It is found ex- clusively in cases of diphtheria, in or beneath the false membranes; has been in vain sought in the blood and viscera. Culture experiments, made first by Loeffler in 1884, subsequently by Roux and Yersin, appear to have been successful; and with the product of pure cultures, the disease in all its essential features— not even the secondary paralysis in the experiments of the French bacteriologists being lacking— has been reproduced in animals. These experiments have been in part confirmed by Kolisko and Paltauf, of Russia, and by Drs. Welch and Abbot, of the Johns Hopkins Hospital; the latter have noted the invari- able concomitance of the Klebs bacillus with the false membranes of true diphtheria. Other associated microbes, which doubtless have a role in the necrotic phenomena, have been observed in diphtheritic mem- branes, notably the Streptococcus diphtheria of Prudden, which seems to be identical with the Streptococcus erysipelatodes and the Streptococcus pyogenes. Prudden, in fact, assigns to this micro-organism the principal part in the production of false membranes. 2. With regard to the second question, while there is not yet unanimity among the authorities, there seems to be preponderant evidence that diphtheria is primarily a local disease, the microbe first causing a local inflammation, necrosis, and fibrinous exudation, then elaborating in the false membranes a peculiar poison— a toxalbumen,— which is absorbed, infects and prostrates the organism. It is true that there are difficulties attending this view in its application to all clinical cases; the gravity of the phenomena of infection is not always in pro- portion to the extent of the false membranes, and with an inconsiderable amount of local lesion the pa- tient may from the first be overwhelmed by the toxic accidents. Cadet de Gassicourt makes much of this argument, and classes such cases under the head of "diphtheria of hypertoxic form." On the other hand, it is equally true that there are benign cases where, with well defined patches of false membrane covering considerable areas, the constitutional symptoms are trifling and almost nil. There seems to be no better way to arrive at a true conception of diphtheria than by pathological experimentation, the results of which always bear out the view above stated of a primarily local origin of the disease. This is not the place for a statement of facts such as Oertel has given in his article on " Diphtheria " in the first volume of Ziemssen's Cyclo- paedia, and which show conclusively that diphtheria, when induced in animals by the inoculation of bits of false membrane, is always at first local, fixing itself at the point of infection, and thence radiating inwardly. In harmony with this induction is the experience of Roux and Yersin with the soluble filtrates of diph- theritic cultures, which, injected in animals, produce septic accidents identical with the general constitu- tional effects of diphtheria in man. In accord with this doctrine, we may explain the grave hypertoxic cases as cases of unusual susceptibility to the disease, where the poison, though coming from only a small centre, is rapidly absorbed, and meets with but feeble resistance. In the benigti cases alluded to, though the diphtheritic focus was of considerable extent, either the conditions for the elaboration and absorption of the poison were unfavorable, or the vital forces of the organism were peculiarly resistant to its influence; we are not without analogies which will enable us to understand such cases in conformity with the view that diphtheria is primarily a local disease. The treatment of diphtheria will naturally vary somewhat in accordance with views held as to its be- ing primarily a local or a general disease. Those who believe in a primarily local origin will naturally have a strong interest in destroying in situ the morbid germs before they have had time to generate their virus and poison the organism. Under the other theory, the indications to promote local antisepsis and limit the spread of false membranes is equally recog- nized; but he who regards the diphtheritic plaques as only the expression of a general disease, bearing the relationship to the latter which the scarlatinal angina bears to scarlet fever, will not so strongly insist on energetic local treatment as he who looks upon the local lesion as the centre of the infection. Those, doubtless, that hold to the latter view have the most sanguine expectation that a specific will yet be dis- covered which, applied in time to the morbid focus, will nip the disease in the bud. Certainly the results of the cauterization treat- ment, carried out with the intent of destroying the microbe /'// situ, have not been remarkably successful, unless we except the apparently favorable experience with carbolic acid and with phenicated camphor of Archambault and Gaucher, at the Hopital des En- fants Malades; of Soulez, of Romorantin; of Sevestre, at Hopital Trousseau; and of Dubousquet-Laborderie {vide Bulletins et Memoires de la Socie'te de Me'decine Pratique, January 15, 1889). The method of these writers has been so highly vaunted that it deserves mention. The phenicated camphor is made of follows (formula given by Sevestre):* 5 Camphor, 20 parts. Castor oil, 15 parts. Alcohol, 10 parts. Crystallized phenic acid, 5 parts. Tartaric acid, 1 part. Dissolve the phenic acid in the alcohol, add the camphor, then the tartaric acid, and finally the oil. * Sevestre: " Etudes de Clinique Infantile," 1S90, p. 210. Gaucher applies this preparation in the following way: " The mouth being widely opened and the tongue depressed, the operator will carry the swab charged with the liquid into the back part of the throat, apply- ing it to the tonsils or other parts that are covered with false membrane. He will rub vigorously the diseased surface, in order to detach and remove the diphtheritic membrane, which will come away in debris or flakes. After each rubbing, the swab should be washed in a carbolic solution. These frictions should be repeated several times at each seance till all the white patches have been removed or destroyed. A final application with the swab dipped in the caustic will be made to the throat, in order to touch all the surfaces which have been denuded and de- spoiled."! This operation is repeated morning and evening and in the interval of the cauterizations; large irriga- tion-injections are made every two hours into the throat, by means of a fountain syringe, of a 1:100 carbolic solution. The pain of the cauterizations is sometimes very great, but may be mitigated by pre- viously spraying the throat with a cocaine solution. Despite the fact that signal and unparalleled suc- cess is claimed for this treatment (see statistics of Gaucher, Le Gendre, Dubousquet), it will not be likely to come into favor, on account of the painful- ness of the cauterizations, the swelling which follows them (which necessarily hinders deglutition), and the difficulty, if not impossibility, of application in young children. Theoretically, this method is excellent; practically it demands for its execution a pitiless f Bull, et M ^1-39' ^29-80- Inoculated in hares and guinea-pigs, this toxalbu- min kills them in the dose of 2^ milligrammes per kilogramme of the weight of the animal. Sometimes death is delayed for weeks, and even months. The toxalbumin kept in a vacuum may preserve its viru- lence for several weeks. Wassermann and Proskauer have reached the same conclusions as Brieger and Fraenkel. They think that the toxalbumin of diphtheria is not a simple body, but that it contains two kinds of substances: first albu- moses, then the diphtheritic poison properly so-called united mechanically (not chemically) to these albu- moses and endowed with the property of undergoing precipitation with them. This is the secret of the variations observed in the toxicity of the matters des- ignated as toxalbumins, which are found more or less charged with poison, according to circumstances. The toxalbumin isolated by the German chemists is, then, an exceedingly complex body, containing probably great quantities of substances absolutely foreign to the poison itself, since the dried precipitate obtained by Roux and Yersin is a hundred times more toxic to animals than the toxalbumin of Brieger and Fraenkel. — 45 — Gamelei'a puts forth a new conception, viz., that the diphtheritic toxine is derived from certain constit- uents of the bodies of the specific bacilli. This author attempts to show by the action of the soluble fer- ments on this poison that it is decomposable into two substances, one of which produces cachexia in the animals. The reactions place this cachecticizing poison among the nucleins; the primary poison is only a nuclein-compound, it is a nucleo-albumin. Quite recently, Guinochot, cultivating the Loef- fier bacillus in urine free from albuminoid matters, and inoculating guinea-pigs with cultures filtered through porcelain, showed that the animals under ex- perimentation died with the same lesions as the con- trol guinea-pigs inoculated with a culture in bouillon, and that consequently the toxine of diphtheria is not necessarily derivable from albuminoid matters, as affirmed by the German chemists. Moreover, it seems that the toxine itself cannot be an albumin in these conditions, for one cannot find in culture-urine any trace of albuminoid matters by the ordinary reagents (Tanret's test, the biuret test, etc.). Several attempts have been made during the past few years to render animals immune to diphtheria. Already in 1887 Hoffman had observed that guinea- pigs inoculated with old cultures spontaneously atten- uated remained refractory to inoculation with recent cultures certainly virulent. Fraenkel and Brieger have shown that by inoculating guinea-pigs with ten _ 4 6 - to twenty cubic centimeters of diphtheritic culture bouillon three weeks old and heated between 65 ° and 70 C. for one hour, the animal is rendered refractory to subcutaneous inoculation alone. The immunity is not acquired during the first few days which follow the protective inoculation, for at this time an inoculation of a virulent culture would be more rapidly followed by death than if there had been no previous inocula- tion. It is only at the end of a fortnight that the ani- mal may receive under the skin the virulent bacilli of diphtheria. Moreover, if animals be inoculated with the Loeffler bacillus, and immediately or after a few hours again inoculated with cultures heated to 65 and 70 C, the subjects die more rapidly than other- wise. These authors contend that the diphtheritic bouillon contains two principles: a toxalbumin which loses its virulence at 70 C, and a second substance that can withstand higher temperatures and is capa- ble of conferring immunity. These results do not involve any therapeutic ap- plication. I shall only mention the tentatives of vac- cination of diphtheria practiced on animals and even on children by Ferran; they were far from being suc- cessful. But this is not the case with the experiments of Behring. This savant has succeeded in conferring immunity on animals by different processes: (1) by the method of Fraenkel and Brieger, just stated; (2) by inoculating the animals several times with cultures of diphtheria containing constantly decreasing doses of — 47 — trichloride of iodine; (3) by using the pleural exudate found in the cadavers of animals dead of diphtheria; (4) by injecting either trichloride of iodine, or chlo- ride of gold and sodium, in animals already inocu- lated with the Loeffler bacillus; (5) by making sub- cutaneous preventive injections with oxygenated water, and then inoculating with the diphtheritic germ. Behring has injected the blood of a guinea- pig thus immunized into the peritoneum of other guinea-pigs; he has been able by this means not only to confer imnunity — and an immediate immunity — but he has also succeeded in curing animals pre- viously inoculated with the Loeffler bacillus. He has also remarked that this preservative and curative ac- tion of the blood of animals that have acquired immu- nity is not permanent, but diminishes with time. He thinks that the blood of immunized animals has no microbicide but only a toxicide action; which suffices to explain its effects. In any event, the short duration of the immunity confeired shows plainly that we are not here dealing with a true vaccination, and thai the blood of immunized animals has no other properties than those of an antitoxic substance. Behring has quite recently published a new method of vaccination. The diphtheria bacillus cul- tivated in bouillon made from calves' thymus pro- duces a very feeble toxine. To prepare this bouillon, take two or three fresh thymus glands, hash them fine, and add an equal quantity of distilled water; - 4 8 — macerate twelve hours in a refrigerator; strain and express carefully. Add to the filtrate equal weights of carbonate of soda and distilled water in quantities sufficient to prevent precipitation in heating up to ioo° C. for fifteen minutes. After this the liquid be- comes grayish-brown; then filter anew through linen to remove the woolly-like flakes that form; pour into culture-tubes, and sterilize in the autoclave. Sow this bouillon with the virulent Loeffler bacillus. When the toxine is well developed, heat the culture up to 65 or 70 C. for fifteen minutes. By this means you eliminate the toxic principle, and there remains only the vaccinant principle. Then inject into the peritoneum of a guinea-pig 2 (two) Cc. of this heated culture. This injection is to be repeated two days afterward, and then at the end of four days. Nine days after the vaccinant injections, the gumea- pig is inoculated with one milligramme of a very vir- ulent diphtheritic culture, and resists the inoculation, but at the point where the injection was made there will be oedema, then an eschar, in which is found the living diphtheria bacillus. This demonstrates that the immunizing injections have, strictly speaking, an antitoxic, but not a vaccinant, property. SECONDARY INFECTIONS IN DIPHTHERIA. We know that in most diseases, to the primary infection provoked by the specific microbe are added secondary infections due to the intervention of other pathogenic bacteria. These bacteria thus contribute to a transformation of the disease, whether by pro- voking local troubles at the point of inoculation, or by distant complications, or by infecting the entire organism through the circulation, or by poisoning the economy by the toxines when they develop. It cannot be said, however, that we have yet isolated and studied all the microbes which are met with in the false membranes along with the Loeffler bacillus. Several evidently are pathogenic, but re- searches have thus far pertained to only a few of them. We know that the Strepto-occiis pyogenes is found very frequently in the false membranes of the diphtheritic. It is not likely to remain confined to the part affected, but may pervade the entire organ- ism through the blood, or find a lodgment in some distant point. Its association with the Loeffler ba- cillus may be expected to give rise to the hypertoxic forms of diphtheria, veritable septicaemias, in which the microscope shows the presence of the streptococ- cus in the blood of every part. This streptococcus is found in a state of purity in the suppurations which sometimes accompany diphtheria. It has been found in the otites, the adenites, the phlegmons of the neck, - 5° — the suppurations of the trachea consecutive to trache- otomy, the arthrites, and even in mediastinitis accom- panied with pleurisy and pericarditis. This microbe has been especially studied in diphtheritic broncho- pneumonias, where it has been found associated with the Talamon-Fraenkel pneumococcus, and where it seems to play the principal role. It has also been detected in the vegetations of endocarditis superven- ing in the course of diphtheria. Lastly, it may give rise to a grave erysipelas, which will make the prog- nosis sufficiently gloomy. Not so well known is the role of the staphylococ- cus {aureus and albus) which has also been found in the false membranes and in the air-passages and lungs- affected by broncho-pneumonia, along with a certain number of cocci not yet classified. This is about all that we know as to the second- ary infections of diphtheria; and I shall have finished this division of the subject when I have said that the Loeffier bacillus confers no exemption from the con- tagion of measles, scarlet fever, and whooping-cough. THE PSEUDO-DIPHTHERITIC BACILLUS. In his first researches on the bacillus of diphtheria, Loeffler found this bacillus with all its morphological characters in the saliva of a healthy child. In a second memoir, he describes a bacillus found in the pseudo-membranous products very like the specific bacillus, but differentiated by certain characters of its cultures, and especially by the absence of all patho- genic action on animals. Since then, this bacillus has been well studied by Hoffmann, Zarniko, and espe- cially by Roux and Yersin. When several tubes of gelatinized serum are sown in streaks with false mem- branes, especially if these are taken from a case of benign diphtheria, we sometimes find in the midst of numerous colonies of very virulent bacilli one or more colonies which produce no effect on animals by inoculation. If you sow on serum in the same manner mucus taken from the throats of patients affected with anginas not diphtheritic (rubeolic angina espe- cially) you will sometimes observe in one of the tubes sown (and generally in not. more than one) several rare colonies of bacilli offering all the characters of the diphtheritic bacillus except its virulence. Inocu- lated in animals, they are inert.* * Among the distinctive features of this pseudo-diph- theritic bacillus is its rarity. Out of several tubes sown with diphtheritic membrane, you will find scattering colonies <>f the pseudo-bacillus in only one or two; in the sore-throat of — 5 2 — The pseudo-diphtheritic bacillus stains like the virulent bacillus by the Loeffler blue, by Roux's blue compound, and by the method of Gram. When the process is examined under the microscope, it will be seen that the bacilli undergo the staining uniformly, or else appear granular, the staining matter having an elective action upon certain points. The bacillus is a rod, straight or curved, with roundish (sometimes swollen) extremities, quite like the diphtheria bacillus, but (according to Loeffler) not quite so long. Sown on serum at 37 C, the pseudo-diphtheritic bacillus yields vigorous colonies, growing as quickly and pre- senting the same appearance as those of the specific bacillus. On gelose the aspect of the colony is identical with that of the diphtheritic bacillus, but there is difference of growth which is sufficiently marked, especially at a moderate temperature, in favor of the former. When cultivated in bouillon, the pseudo-diphtheritic deposit is thicker and whiter than that of the virulent bacillus, and the bouillon remains alkaline instead of becoming acid (Zarniko). Roux and Yersin dispute this latter point; both ba- cilli, they say, render the bouillon acid, then alkaline, but the change of reaction is more speedy in the case measles, it is seldom that these bacilli are found in any abundance, and the inoculation test shows them to be rela- tively harmless. Recently Ortmann found this pseudo-diph- theritic bacillus in a case of purulent meningitis associated with the pneumococcus. — 53 — of the pseudo-diphtheritic bacillus. The cultures of the latter on gelatin at 20 C. are more abundant than those of the Loeffier bacillus, and the latter grows more abundantly in a vacuum than the former. Moist heat kills the pseudo-diphtheritic bacillus at 68° C. in ten minutes; just as it does the Loeffier bacillus. Animals the most sensitive to the diphther- itic virus resist inoculation with the former; nothing at the most is seen but a little oedema at the point of in- oculation in guinea-pigs; the most marked cedemas being caused by the bacilli from rubeolic anginas. Likewise inoculation by its filtered cultures is gener- ally inoffensive, though large quantities cause emaci- ation and finally death. Many authorities admit, with Loeffier, that the inoffensive bacillus is very similar to the virulent bacil- lus. They base their differentiation on the points I have mentioned: the pseudo-diphtheritic bacillus is shorter, cultivates more vigorously and at a lower temperature in different media, and grows more spar- ingly in a vacuum; if its cultures in bouillon at a given moment present the acid reaction, this reaction lasts but a short time; lastly, neither the bacillus nor its filtered cultures are found virulent to animals. These differences do not seem to Roux and Yer- sin sufficient to carry conviction. They say they have seen the benign bacilli yield, for the first few days, cultures as poor as those of the virulent bacillus. Moreover, abundance of culture has never sufficed to — 54 — characterize a microbe. The morphological differ- ences are so feeble that they prove nothing. There remains the question of virulence. But these authors have carried on the attenuation of virulent cultures placed at 40 C. in a current of air, and these cultures became inoffensive to animals, whereas previous to attenuation they would have been sure death. Nay, more, these attenuated bacilli take on in cultures the characters of the pseudo-diphtheritic bacillus; they grow better than the virulent form in the air and at a low temperature, and not so well, on the contrary, in a vacuum. Lastly, when a large quantity of their filtered culture is injected into guinea-pigs, these ani- mals grow thin and cachectic, sometimes even die at length — a result just like what we get with massive doses of the filtered culture of the pseudo-diphtheritic bacillus. The demonstration would be complete if Roux and Yersin had succeeded in rendering virulent the pseudo-diphtheritic bacillus. Unhappily, all their tentatives in this direction have been in vain. De- spite this failure, they are disposed to affirm the iden- tity of the two bacilli. " Under the influence of an eruptive fever or of some unknown microbian associ- ation, the pseudo-diphtheritic bacillus takes on viru- lence and becomes the active diphtheritic poison. This is only a hypothesis; but as we have proved that the virulent bacillus of diphtheria may be attenuated so as to be indistinguishable from the pseudo-diph- — 55 — theritic, it is not unreasonable to suppose that this pseudo-diphtheritic bacillus plays a role in the etiology of diphtheria. It is still very difficult to define the role. Most cases of diphtheria are surely due to direct contagion, whether by means of fresh or of dried virus; but alongside of these diphtherias coming directly from a virulent bacillus, there probably exist some which have for their origin this pseudo-diph- theritic bacillus, parasite of so many mouths. Becom- ing virulent through conditions which we cannot yet explain, it may be the starting-point of new conta- gions. The idea that a saprophyte microbe may be- come pathogenic has been introduced with authority into science by the experiments of the laboratory of Pasteur on the attenuation of virus and its return to virulence. It was set forth in a note by Pasteur, Chamberland, and Roux in 1881; since then it has been accepted by many savants, and we think it a fruitful notion which explains many facts otherwise inexplicable." FALSE DIPHTHERIAS. Writers have long discussed the nature of certain pseudo-membranous products which objectively are confounded with the diphtheritic false-membrane, but differ by the concomitant symptoms and by the course of true diphtheria. Such is the grayish exudate which is found on inflamed wounds and ulcers, on blisters badly treated, on patches of intertrigo that have been irritated; such are the false membranes of the so- called diphtheritic form of puerperal fever, the pseudo- membranous products which sometimes extend over the infectant chancre or secondary syphilides, those which cover the lips of children affected with measles, which supervene in the course of simple anginas, and especially at the onset of scarlatina. Bacteriology alone can settle any doubt in this matter by showing that these false membranes do not contain the Loeffler bacillus. It is probable that there are several bacteria capable of provoking fibrin- ous exudations which undergo organization into false membranes. Among these are the golden and white staphylococci, the streptococcus pyogenes, and the Talamon-Fraenkel pneumococcus. Experimentation has shown that with the streptococcus pyogenes found in puerperal diphtheroid patches, in certain anginas with suspicious pseudo-membranous exudates, and in the early pseudo-diphtheritic anginas of scarlet fever, we may succeed in reproducing false membranes of — 57 — considerable extent and toughness upon the excoriated mucous membrane of the beak of pigeons. I have also isolated the staphylococcus aureus from the white, thick patches adherent to the stomatitis of patients suffering from measles. Lastly, I have found the pneumococcus in pseudo-membranous angina and laryngitis. All these affections, where the Loeffler bacillus is wanting, merit the name of false diphtheria. With diphtheria they have nothing in common but the false membrane, and they are distinguished by the absence of the characteristic intoxication which the specific bacillus produces. We shall study them more completely in connection with the diagnosis of diph- theria. 6 uuu ANIMAL DIPHTHERIA. There exists in several species of animals, notably in birds, a disease characterized by a false membrane very like that of human diphtheria. This sometimes appears in the trachea, causing asphyxia, with stridu- lus breathing similar to that of croup. This aviary diphtheria is believed by some writers to be identical with the malady as found in man. These writers point to the frequent coincidence of epizootic pseudo- membranous diseases among fowl with epidemics of diphtheria among men, and the undeniable fact of the experimental infection of pigeons and other birds by the Loeffler bacillus, the ensuing malady exhibit- ing the main features of the disease as it prevails naturally among birds. But these statements of con- tagion have been disputed, and numerous instances in contradiction have been given. Let us see what data we actually possess respecting animal diph- theria. Competent observers have noted pseudo-mem- branous affections in birds, cattle, hares, cats, sheep, and hogs. The diphtheria of birds attacks chiefly pigeons, hens, pheasants, and some wild birds. It is epidemic and contagious; is often met with in barn- yards and henneries, where it decimates the fowl; is characterized by false membranes about the beak, mouth and throat, the nares, the larynx, and some- times the intestine. The malady may localize itself — 59 — in one patch, or may spread and even invade the entire mucous tract. There exists a visceral form of this affection, with fibrinous deposits resembling, at first sight, miliary tuberculosis. You may even re- produce all these forms by applying to the different mucosae the virulent matters of aviary diphtheria. The most frequent and best known form is that com- monly called the pip. This exhibits grayish false- membranes covering the tongue, throat, nasal fossae, and finally obstructing these passages by its exuber- ance. When this exudate is removed, the mucosa is seen to be eroded underneath; but the false mem- branes are speedily reproduced. The bronchi or the conjunctivae may be secondarily invaded. On pal- pating the cutaneous surface, you often discover little fibrinous nodules. This disease often lasts days, weeks, and even months. Megnin has described a latent form of the diph- theria of pigeons, in which the adult birds preserve all the appearances of health and have only little diphtheritic pellicles in the oesophagus, but may transmit a fatal diphtheria to their young. The prognosis is grave, without being necessarily hopeless. There are numerous little cutaneous tumors contain- ing a yellow fibrinous matter of caseous aspect. False membranes invade the conjunctivae, the nares, the trachea, and even the intestine. Below the exu- date, there is congestion of the mucosa and infiltration of the subjacent parts. — 6o — Aviary diphtheria attacks young birds especially, it is transmissible to other animals, notably cats. The specific microbe of aviary diphtheria is a rod resembling that of human diphtheria, but somewhat shorter, with extremities not swollen. It grows on gelatin at 17 or 18 C, and does not liquefy the gelatin; its colonies spread widely on the surface of the gelatin. On potato it gives a thin, grayish cul- ture. Loeffler inoculated four pigeons with this ba- cillus; he obtained inflammation at the point of inocu- lation, and a false membrane. Two of the pigeons died, and the bacillus was found in the lungs and liver. This bacillus is less active than that of human diphtheria in the hare, the guinea-pig, and the dog. Injected into hens, it produces only lenticular spots at the point of injection, without general empoisonment. Hence Loeffler thinks that the diphtheria of hens is not identical with that of pigeons. These researches have been confirmed by Babes, Puscariu, and Krajewski. Recently Haushalter isolated from the false membranes of hens affected with diphtheria, a ba- cillus which he considers as the specific agent of aviary diphtheria. Morphologically this bacillus re- sembles that of tuberculosis, but its length is variable. It does not liquefy gelatin. On gelose at 37 C. it forms a membranous elevation, white and smooth. It develops well at 37 C. on gelatinized serum; and gives rise to a grayish, moist, elevated papule on — 6i — potato at 37 C. The sown bouillon rapidly becomes turbid, and deposits a powdery sediment. The injection of these cultures into the blood of the hare, provokes diarrhoea and fever; the animal, however, recovers. Subcutaneous injection of the bacillus provokes suppuration. Inoculated in the pectoral muscle of a pigeon, it kills in less than forty- eight hours, and the bacillus is found in the blood. This bacillus is also pyogenic to hens. Bovine diphtheria is quite common in Germany, though unknown in France. It constitutes veritable epizootic epidemics. The animal is taken with ex- treme lassitude, with fever and prostration, has rigors, refuses to eat, and rapidly emaciates. There is an abundant flow of saliva; the snout is wide open; the tongue hangs out of the mouth and is almost always swollen. The swelling extends to the whole of the buccal mucosa, which is covered with yellow patches of exudation penetrating deeply into the mucosa, which is often eroded. These false membranes often have a thickness of one and a half centimeters. The pituitary, laryngeal, and tracheo-bronchial mucosae may be invaded in their turn; then there is a yellow- ish discharge, the respiration is labored and stertor- ous; there is sometimes pneumonia or pleurisy. The exudate is seen on the conjunctiva, in the interdigital space, and about the sheath. Often the animals are affected with pseudo-membranous enteritis, which manifests itself at first by constipation with hard — 62 — faeces covered with false membranes; then diarrhoea sets in, sometimes dysentery, almost always followed by death. The laryngo-pharyngitis, though less fatal than the enteritis, kills not less than four animals out of five. At the necropsy you will note cedematous infiltration below the mucous membrane which is covered with false membranes, and pseudo-membran- ous nodules in the skin, cellular tissue, muscles, liver, and lungs. The latter are often hepatized, some- times gangrenous. The virulent agent of this disease 'exists in the false membrane, the nasal discharge, and in the diar- rhceal liquid. With these products a pseudo-mem- branous affection may be provoked in calves, birds, hares, and sheep. .Loeffier has examined the false membranes of the buccal cavity in seven cases. On preparations stained with alkaline methylene blue the superficial stratum stains strongly with blue; be- low this there is a large zone unstained; then the deep layer forms a colored band. The first stratum contains a great variety of micro-organisms, especially cocci; in the deep part are seen bacilli united in long undulating filaments. These bacilli measure half the length of those of charbon; Loeffier considers them specific in bovine diphtheria. There exists in cats a disease characterized by dysphagia, inflammation of the palate and throat, and dyspnoea. The conjunctiva is sometimes red. The animals emaciate, cough, and have bronchial catarrh. _ 6 3 - Most cases recover, but the disease may last a long time. In one case there was paralysis of the hind limbs. Klein says the disease is transmissible to man. He found false membranes in the trachea and bronchi in three cases. Sections of this exudate stained showed in only one instance bacilli resembling the Loeffler bacillus; in the other two cases, where death was late, he found no bacillus. Sowings on various culture-media remained sterile. These facts are clearly insufficient to identify human diphtheria with the diphtheria of cats. Ribbort has studied in the hare a disease which produces acute fibrinous peritonitis, with swelling of the mesenteric glands, and characterized chiefly by the lesions of pseudo-membranous enteritis in the large and small intestines. He has isolated from the false membrane a bacillus 3 to 4 pi long and 1 to 1 /< 4 broad, which grows well in gelatin without liquefying, and forms grayish colonies on agar and on potatoes. Subcutaneous inoculation of this bacillus determines a sort of septicaemia in the hare; in the throat it develops false membranes on the tonsils. In dogs there is often a sort of pseudo-membran- ous angina or stomatitis which is very grave, with fever, dysphagia, flow of saliva, and general enfeeble- ment; death supervenes at the end of five or six days. Hogs are also subject to a pseudo-membranous affection. These affections have not yet been studied from a bacteriological point of view. SYMPTOMS. Incubation. — When the Loeffler bacillus has penetrated the economy, before its presence is mani- fested on the mucous or cutaneous surface by local symptoms, and before its toxine has given rise to general symptoms, a variable time intervenes during which the infection remains latent; this is the incuba- tion period. Statistics prove that the duration of incubation is generally from one to three days, but exceptionally from twelve to fifteen days. Experi- ments on animals have indicated that the time which elapses between inoculation and the first manifesta- tion of the disease is proportionate to the quantity and virulence of the virus injected. It is probable that the soil on which the infection develops, and the resistance of the organism, play an important role, of which it is still impossible to measure the value. Clinical Study of Diphtheria. — We know now how the Loeffler bacillus acts on the organism; it fixes itself and forms colonies on the eroded mu- cous membrane or denuded derm, and produces a false membrane there, where it lives confined, devel- oping and multiplying outside of the organism. To these local manifestations are joined general acci- dents, functional troubles of organs remote from the point of infection. No one has ever found the Loef- fler bacillus in the blood or viscera; we must then re- fer these general disorders to the systemic poisoning - 65 - by the products of the diphtheritic bacillus, and to similar infections by other pathogenic bacteria whose association complicates the disease or may even com- pletely alter the clinical aspect. We know that the diphtheritic poison penetrates the circulation; it is easy to demonstrate this, for the urine of the patients contains a notable proportion of this poison; and if we inject this urine in animals we produce in them lesions identical with those which are consecutive to inoculation with the Loeffler bacillus or with the filtered bouillon. This poison fixes itself in most of the organs — the liver, the spleen, the kidneys, the heart, the nervous system, etc.; for a maceration of these organs injected into guinea-pigs and hares kills them, with all the lesions characteristic of diphtheria. It is certainly to the toxine that we must refer the alterations noted in these organs in diphtheritic pa- tients, for no bacteria are found there. This is not the case when certain complications exist, such as the suppurations, the broncho-pneumonias, which are often superadded to the diphtheria; we have seen that these owe their origin to new infections by microbes other than the Loeffler bacillus. It will be convenient to consider this subject under three heads: the first comprises the symptoms of bacillary infection; the second, those of systemic poisoning; thr third, the complications due to second- ary infections. Diphtheria sometimes begins by local, sometimes — 66 — by general, symptoms. In the latter case, the Loeffler bacillus has already been multiplying in an infected point, but has not yet produced the false membrane. Often, also, the disease is announced by symptoms at once local and general. The onset may be sudden, with great gravity, or slow and insidious. In chil- dren it is not rare to see diphtheria begin suddenly with a high fever, with a temperature of 40 C, and often with chills, vomiting, delirium, and convulsions,, lividity of the skin, etc.; and it may be only accident- ally that attention is directed to the throat. I. Symptoms of Bacillary Infection. — Diph- theria manifests itself by the development of a false membrane, at first thin, whitish, opaline, of rather softish consistence. This membrane may be seated on a mucous membrane or on any part of the skin; it is met with, in order of frequency, in the throat, larynx, nares, trachea, bronchi, mouth, Eus- tachian tube, middle ear, conjunctiva, prepuce, glans penis, anus, scrotum, and uterus; is extremely rare in the oesophagus, stomach, and intestine. In the sta- tionary period of the disease, the false membrane is firm and elastic; may generally be detached in large flakes with an ordinary swab or with forceps. Below, the mucosa or derm is rarely ulcerated, but bleeds easily. If a removed shred of the pseudo-membrane be agitated in a glass of water, it will not dissolve. The false membranes form at points where they give rise to little lenticular concretions, or oftener to exten- - 67 - sive circular patches or strips. Often they take the form of the organ on which they rest: the larynx, the Eustachian tube, etc. Exceptionally they have been known to take on extraordinary dimensions— in one instance, covering the skin from the neck to the sacrum. At first smooth, they soon become rugous; their sur- face is grayish, sometimes yellowish, or it may be brown, colored by the blood, and resembling a gan- grenous eschar — in very grave forms the fetid odor of the latter is noted - the consistence being pulpy, and the exudates forming a putrid and sanious magma. When the diphtheritic patient recovers, the false membrane softens, disintegrates, and disappears. One of the principal characters of the false membrane is its ability to reproduce itself repeatedly. When it is removed, the mucosa underneath remains at first bare, but in the course of a few hours the fibrinous exudate is re-formed; and this process will go on as long as the disease lasts. The false mem- brane has also the property of being essentially in- vading; it rarely remains localized to the point where it first forms, but spreads to contiguous regions; starting in the throat, it ascends the nasal foss?e, or spreads downward into the trachea. The particular seat of the false membrane de- termines in some measure the concomitant local symptoms. Diphtheria usually begins with a sore throat. There is nothing at first to excite alarm: a little redness and swelling of the velum pendulum - 68 — and tonsils; a sensation of dryness in the throat (there is yet no false membrane —it is the congestive period). After a few hours the mucous membrane exhibits a thin coating of mucus, partly concrete, which soon changes into an opaline patch, half transparent, but little adherent; this is the false membrane. From the first, there is a notable engorgement of the sub- maxillary glands, which become larger as the disease progresses. The false membrane is first seen on one or both tonsils; it may invade the soft palate or uvula, or extend to the nasal fossae and larynx. The pain generally remains slight and supportable; but the dysphagia, which was scarcely noticeable at first, generally augments as the false membranes extend. The voice takes on a nasal twang. The respiration is a little oppressed when there is hypertrophy of the tonsils, and especially when there is coryza. At whatever point the diphtheria develops, it always presents the local symptoms of an ordinary inflammation, with this phenomenon superadded: the formation of a false membrane. But when the disease invades the air-passages, it adds a new element to the symptom-picture and a factor of gravity to the prog- nosis: the mechanical obstacle which the false mem- brane interposes to respiration. In most cases, croup is preceded by a diphthe- ritic angina, and supervenes upon the latter in the course of the first week of the disease; sometimes all the characteristic symptoms appear from the very - 69 - onset. In primary croup, the laryngeal symptoms appear in the midst of apparently perfect health, or follow a slight cold or catarrh of the bronchi. Excep- tionally, the croup is ascendant — the bacillus having primarily affected the bronchi. It is customary to describe three periods in the progress of croup: (a) Period of Invasion: The patient complains of a little pain in the region of the trachea, speaks in a hoarse voice, and has a loud, hoarse, barking cough. More rarely the onset is sudden, as in stridulous laryn- gitis; a child, only a little hoarse the evening before, is awakened in the middle of the night by violent attacks of a hoarse, resonant cough; quiet follows, but the respiration gradually becomes difficult and interrupted. This first period may last several days, but sometimes the paroxysms of suffocation come on at the end of several hours, or even at the onset. {b) These paroxysms characterize the second period; the voice and cough are extinguished; dysp- noea becomes constant, with frequent attacks of suffo- cation; the latter come on sometimes spontaneously, without apparent cause, but sometimes are excited by emotion. All at once, with pale face and wild, staring eyes, the child starts up in bed in the anguish of suf- focation—clings to the bed-post — and, with head thrown back and mouth wide open, dilates the thoiax to its utmost. Inspiration is whistling, convulsive, painful, prolonged; expiration generally slow and laborious. At times, the child in coughing clutches at its throat, as though trying to rid itself of the ob- ject that is causing suffocation; the countenance all the time becoming livid. The attack lasts ten min- utes or so, and may terminate in death. Oftener there is another period of calm, during which the breathing improves, the color comes back, but respi- ration still remains noisy and embarrassed, till a new attack sets in. Sometimes there are no paroxysms of suffocation, but the dyspnoea gradually and without intermission becomes worse and worse. The obstacle in the larynx hinders the entrance of air into the bronchi; so when the thoracic cavity dilates in inspiration, the intra- thoracic pressure falls; there is a sort of aspiration of the abdominal organs from below upwards; the epigas- tric hollow is strongly depressed, instead of project- ing as in the normal state (substernal suction). As the glottic cleft becomes more obstructed, inspiration will be attended by a second depression at the lower part of the neck above the sternal notch. This dyspnoea is sometimes temporarily relieved by the expulsion of false membranes, which may show an exact moulding of the bronchial tree. Then the child becomes quiet and somnolent, and ceases to struggle against the asphyxia which is growing more and more pronounced. (c) The third period has now set in. The tegu- ments are cyanosed; the cheeks and lips are purple; — 7i — the extremities cold; the patient lies limp, inert, stupid, rousing from time to time when harassed by a paroxysm of coughing, then falling back and sur- rendering to the progressive asphyxia, and no longer responding to any excitation. This condition fre- quently yields to a state of complete resolution, very like coma; the patient may die suddenly in a parox- ysm of suffocation, or in convulsions. If, as rarely happens, croup which has arrived at this period terminates in amendment and recovery, the cough becomes more noisy and more moist, the dyspnoea diminishes and disappears, but the voice remains long husky. We shall see further on, that croup does not have the same aspect in the adult as in the child. Even in benign diphtheria it is a common thing to note a little coryza with serous discharge. But only in the malignant forms is there invasion of the nasal fossae by the false membrane; there is then red- ness of the nasal mucous membrane (which is covered with crusts), and a sero-mucous flow, often fetid and sanguinolent, which excoriates the skin of the upper lip; false membranes cover the turbinated bones. The specific bacillus may pass from the nares into the nasal duct, and the pseudo-membranous exudate in- vade and close the latter, producing a persistent flow of tears. The inner angle of the eye is soon invaded, and the false membrane spreads over the conjunctiva. Ocular diphtheria is, however, quite rare. — 72 — At the anus, vulva, or meatus urinarius, the medical attendant will sometimes notice diphtheritic patches, which generally appear secondarily to a diphtheria of the pharynx. Excoriated parts of the skin, lips, and nares, the surface of wounds (espe- cially those of tracheotomy), burns, leech-bites, etc., may be the seat of false membranes. Whenever, in fact, in a diphtheritic patient, you see an erosion of the skin, you should close it immediately by an anti- septic dressing. You cannot be too careful, especially in children, in the employment of sinapisms, for if you obtain a blistered surface you have a new seat of in- fection to deal with. When diphtheria invades the skin, the excoriated surface first becomes red, then is covered with false membranes. Phlyctenular appear around the infected point, break, and in turn become covered with false membrane. Often the affected parts take on a gangrenous appearance. The de- nuded derm also absorbs the diphtheritic poison, just like the mucous membrane when invaded by the dis- ease. II. Symptoms of Systemic Poisoning. — From the onset, unless the form of diphtheria be very benign, it is easy to see that the entire organism is smitten. The fever, the extreme pallor (often leaden hue), the general enfeeblement, the glandular engorgement, the albuminuria, the haemorrhages, are so many proofs that the poisoning follows close on the infection, while the myocarditis and the nervous troubles which — 73 — later supervene demonstrate that the poison survives the bacillus. In the gravest forms the patient lies apathetic, shows an invincible repugnance toward food, and ex- presses by his features and his aspect extreme lassi- tude and profound prostration. The fever is always variable and presents but few indications; is not, in fact, a characteristic symp- tom. In grave forms it may be nil, and in the most simple cases (even at the onset) extreme. Hence a high fever at the beginning should not alarm; has not a long duration, and does not cause depression of the forces. Generally in the first few days the tempera- ture does not exceed 38.5 or 39 C. — that is, it is lower than in an ordinary quinsy sore-throat. It is also rare to note chills at this period. During the stationary period the temperature varies according as the disease advances toward recov- ery or death ; if the former, the fever persists for several days, then the temperature suddenly or after several oscillations falls to the normal; a fatal termination, on the other hand, is generally preceded by a rising or permanently high temperature — exceptionally, how- ever, the temperature falls below the normal, when the extremities become cold and cynosed and the patient succumbs in complete algid collapsus. If any complication supervenes, the temperature remains elevated or rises again; such ascensions are observed when the false membrane is reproduced or grafts itself — 74 — on a new point, or when there is broncho-pneumonia, albuminuria, or paralysis. The pulse line is more regular than that of the temperature; in general the pulsations are frequent — 1 20 to 140 per minute— and often do not become slower until the temperature has returned to the nor- mal. The more malignant the form of the disease, the more weak and rapid the pulse, though it may in some cases be abnormally small and slow. The acceleration of respiration is proportioned to the rise of temperature. The glandular engorgement is constant in diph- theria. The submaxillary, parotid, and supra-hyoidean glands are the most markedly swollen. The glandular tumefaction corresponds to the degree of intoxication; it develops early; the glands are taken singly or in groups; their size varies from that of a hazelnut to that of a walnut; they are painful to pressure, and the skin over them is a little hot and sometimes red. In the malignant forms the glandular engorgement takes on extraordinary proportions; there are then regular diphtheritic buboes; the cellular tissue which surrounds them is infiltrated and blended with the inflammatory mass so that the region is completely deformed. If the cervical glands are the seat of the engorgement, the tumefaction is so considerable that the neck appears larger than the head which it sup- ports. These adenopathies may suppurate by reason of a secondary infection by the pyogenic microbes. — 75 — The urine is generally scanty and high-colored, depositing urates copiously; in some cases, however, it is clear and transparent. The average urinary ex- cretion in cases that recover is 300 to 400 grammes in the twenty-four hours; in fatal cases the quantity may fall below 100 grammes, and there may even be complete anuria. Tracheotomy is generally followed by diuresis for two or three days. The density of the urine is always high, without, however, exceeding 1.028 in favorable cases. Urea is augmented, and rises to 12 and 15 grammes per liter, instead of 10; but in cases that terminate fatally the figure may fall to one gramme per liter. The urine in diphtheria is albuminous in more than two-thirds of the cases. Albumen may be found from the onset, or, as is oftener the case, from the third day — during all the stationary period, or at the end of the disease. Sometimes its disappearance coexists with a new development of false membranes. Albu- minous urine is generally limpid, of an amber-yellow color, rarely bloody. The deposit examined under the microscope reveals lithates and phosphates, epi- thelium, hyaline or fibrinous casts, and red and white blood-corpuscles. The quantity of albumen varies from a few centigrammes to ten grammes per liter. The albuminuria may be of brief duration, disappear- ing after twenty-four hours, or it may be persistent, even 1 ontinuing a month or two. The abundance of — 76 - the albumen is generally proportioned to the gravity of the diphtheria, but there is no fixed rule about this. Albuminuria in this malady may be looked upon as an epiphenomenon, which may in a certain measure indicate the degree of intoxication of the organism. It is rare to see diphtheritic patients present symptoms testifying to a profound renal lesion. The anasarca accompanying the albuminuria is quite ex- ceptional. There may be only a little oedema about the face. Sanne cites a case of oedema limited to the glottis, suggestive of croup. Uraemia is infrequent; when supervening, it takes on the eclampsic or coma- tose form. The digestive functions are not disturbed at the onset. Later on, the anorexia becomes absolute and constitutes a serious danger. Vomiting is a rather rare symptom; at the onset or prodromic period it is without gravity, but later it is almost a certain sign of serious complication. During convalescence, re- peated vomitings are of unfavorable omen and are often followed by a fatal termination. The vomited matters sometimes (though rarely) contain false mem- branes from the stomach or oesophagus. Diarrhoea coming on at a late stage is generally related to a marked degree of intoxication. The stools are then fetid and sanguinolent, sometimes containing the debris of false membranes. The pro- fuse diarrhoeas often noted in toxic diphtherias have been compared to the diarrhoea observed in hares — 77 — after intravenous inoculation with large quantities of the diphtheritic poison. Haemorrhages are tolerably frequent in diph- theria, and are almost always associated with malig- nant cases. It is especially at the onset that they have been noted, and during the first five or six days. I refer here to the dyscrasic haemorrhages which are dependent on a profound intoxication of the organism. They take place around the false membranes, the latter being thereby infiltrated and stained brown; the bleeding increases after swabbing the diphtheritic patches. The epistaxis of the prodromal period is sometimes very abundant; there is often spontaneous bleeding from the gums, lips, throat, and even pur- pura hemorrhagica has been noted. Haemorrhages into the nerve centres have been the cause of instant death or hemiplegia. The prognosis of haemorrhage in diphtheria is very grave. Cardiac and nervous disturbances characterize the convalescence. (Edema without albuminuria, general or limited to the face or extremities, has been observed from the eighteenth to the twentieth day of the disease. The pathogeny of this oedema is very obscure. When the local symptoms of diphtheria have all disappeared, and the patient is convalescent, some- times an attack of syncope supervenes, which is the first grave symptom of a complication previously latent: myocarditis. This lesion generally manifests - 7 8 - itself five, six, or eight days after the onset of conva- lescence — sometimes a little later, especially in young children. The first symptoms are: occasional palpi- tations, a little restlessness and dyspnoea, frequent pulse, a state of temporary cardiac erethism; then the pulse becomes feeble, compressible, and soft; the heart-beats are obscure and distant, with intermit- tences, and there is pain in the cardiac region. In adults this pain may be so severe as to simulate angina pectoris. Most of these symptoms may be overlooked in children until pallor and collapse sud- denly supervene. This pallor and cardiac failure are exaggerated on making effort, and the patient is always menaced with syncope. The general enfeeble ment continues; vomiting and diarrhoea are sometimes present. The precordial pain augments and becomes agonizing and constrictive. Children do not, how- ever, complain of this pain so much as adults, for children soon fall into collapse. Whatever may be the age of the patient, he is soon the prey of a very marked paroxysmal oppression; lies prostrate, with face livid, features pinched, lips cyanosed; then sud- denly he grows paler, and lies motionless — syncope has taken place. The pulse is irregular and compressible, with occasional intermittences; the feebleness of the pul- sations marks the insufficiency of the ventricular impulse. The physical signs obtained by examination of — 79 — the heart are those of acute dilatation. The precor- dial region presents a slight vaulting; you can see the propagation of the cardiac pulsations from the apex to the epigastrium. The apex is generally found in the fifth or sixth intercostal space, outside of the mammary line. The hand, instead of being raised by a single snock, perceives a series of successive undu- lations and irregularity of the shocks. Percussion indicates an augmentation of the volume of the heart in every direction; but it gives little information in the infant. Auscultation reveals all the types of arythmia possible, with more or less marked obscurity of the sounds of the heart. You may observe tachy- cardia, bradycardia, a bruit de galop, or reduplication of the second sound. Sometimes the first bruit is also reduplicated, and you hear four consecutive bruits. Inversely, one of the two bruits, especially the first, may be wanting. The state of the heart has been compared to that in animals poisoned by digitalis. As the enfeeble- ment of the cardiac muscle augments, there arises a soft systolic bruit, loudest at the apex, essentially transitory. This sign is found in most of the acute myocardites. Lastly, the sounds of the heart become more and more muffled and distant, until only a feeble undulation is perceived, which Lancisi called trem- bling of the heart. Along with these symptoms of cardiac enfeeble- ment the general prostration arrives at its maximum. — 8o — The teguments are ashy pale, covered with a cold sweat, the extremities cyanosed. The patient lies motionless, the respiratory movements scarcely per- ceptible. From the onset of the cardiac accidents, albumen reappears in the urine, but the temperature never transcends the normal, and may fall below it in a period of collapse. Thus it is that diphtheritic myocarditis comports itself: insidious, sometimes fulminant in the child, it follows a progressive course in the adult, who often survives one or perhaps several attacks of syncope; it is, nevertheless, almost always fatal. Generally from eight to fifteen days after re- covery from the local symptoms of diphtheria, the paralysis manifests itself. It may make its appear- ance earlier, even during or at the end of the first week; then again, it may come on as late as a month or two after the patient has apparently recovered. The rule is that the paralysis comes on during full convalescence. It is a very common accident of the disease — existing, according to Roger, in one-third of the grave but not fatal cases. The paralysis may follow the most benign as well as the most severe cases. There have been epidemics in which it was a very marked and almost always fatal symptom. It is not so common in children under ten years of age as in adults. The onset of the paralysis is generally slow and insidious. There is first only a little hesitation of the — Si — motor functions, then deglutition, walking, and other movements become more and more difficult. The paralysis may be ushered in during convalescence by a little febrile rise, or a return of albuminuria. The point of election of the paralysis is the velum pendulum, where it almost always begins, and where it may remain localized; or it may extend to other parts and constitute the generalized form of the dis- ease. When localized in the soft palate, the paralysis is essentially insidious. A slight pallor, a little slowing of the pulse, are the only disturbances of the general state which are noted. The paralysis would easily pass unperceived if the reflux of liquid aliments by the nasal fossa; did not indicate the impediment to deglutition. During the second stage of deglutition, the pharynx contracts on the alimentary bolus to seize it and propel it downwards; normally the velum pendulum falls back and closes the posterior nares, but when this muscular septum is paralyzed a por- tion of the ingesta will enter the nasal fossa;. There is generally at the same time a slight paresis of the upper part of the larynx; the occlusion of the glottis is incomplete, and the patient coughs during deglutition because a few drops of the liquid or par- ticles of food come in contact with the mucosa of the larynx. If the paralysis of the velum pendulum is com- plete from the onset or becomes so subsequently, if — 82 — the pharynx is paralyzed in its turn, the food can only be swallowed after repeated attempts, which soon fatigue the patient and sometimes lead him to- refuse all nourishment. The voice is feeble and nasal, the articulation of sounds difficult, the speech slow; and if the breathing is normal while the patient is awake, it is more or less stertorous during sleep. When the diphtheritic paralysis does not remain localized, it may begin with the velum pendulum, then extend to the muscles of the eyes, of the upper and lower limbs, of the trunk, of the neck, of the rec- tum and bladder, to end with the organs of the special senses. This is the ordinary course of the more com- plete forms of paralysis. More rarely, it may attack the lower limbs before affecting the larynx and the tongue, or even begin with the upper extremities, then invade the velum pendulum and pharynx, and lastly attack the lower limbs. When the paralysis is thus extensive, grave gen- eral symptoms — such as the ashy hue, collapse, rest- lessness—are often present; sometimes vomiting, se- vere diarrhoea, convulsions, and sooner or later coma. But these alarming symptoms are only met with in the very grave cases; and with the exception of a little albuminuria and fever at the onset, the constitu- tional symptoms may be inconspicuous. We shall follow, in the description of the troubles of motility, the usual order of extension of the paraly- sis. Generally affecting the entire surface of the soft - 8 3 - palate, it may be localized and only occupy one-half of this organ and the pharynx. If you titillate the base of the tongue or pharynx, you will see contractions on the side that is not paralyzed. The anaesthesia fre- quently extends to the upper part of the larynx, and this favors the passage of the food particles into the air-passages. After the velum pendulum, the muscles of the eyes are very often attacked. The muscles of ac- commodation are paralyzed; the motores oculorum are affected in their turn, and strabismus (which is sometimes temporary) and ptosis of the upper lid are noted. But generally troubles of vision, referable to a fault of accommodation, supervene; the sight is en- feebled in different degrees, from slight amblyopia to complete blindness; there is hypermetropia, mydriasis, and, if but one eye is affected, inequality of the pupils. Almost all of the ocular muscles may be in- volved in turn. The lower extremities may be paralyzed immedi- ately after the velum pendulum, and sometimes the paralysis is limited to this double manifestation; oftener they begin to be enfeebled when there already exist ocular troubles. The paralysis of the lower ex- tremities generally takes on the form of an incomplete paraplegia. It is announced by formications and numbness in the legs. Walking becomes uncertain; the patient has an incomplete perception of the ground under his feet, and finds it especially difficult — 8 4 - to go up and down stairs; darkness aggravates these troubles of motility. Then the muscular feebleness augments, and walking becomes very difficult if not impossible; at the same time, the paralysis is never complete. The patients, who are still able to stand, move along by dragging or sliding their feet, as though they were fastened to the ground by an enormous weight. When they are confined to bed, the lower limbs still retain considerable power of movement, but without energy or much reliability — Jaccoud calls it rather an ataxia of movement than a paralysis. Brenner divides these phenomena of incoordination into three classes: (i) True ataxia, caused probably by a lesion of the centre of coordination of move- ment; (2) ataxic paralysis, characterized by paresis of certain groups of muscles of the limbs and by the more complete paralysis of other muscles; (3) true paralysis, which may attack equally all the muscles of the limbs, and which may be complete or incom- plete. These ataxic symptoms, joined to the abolition of the patellar reflex and to the eye-troubles, may give rise to a form of pseudo-tabes. Contracture is quite rare. The enfeeblement and even the abolition of the patellar reflex has been often noted. These modi- fications are seen from the onset of the paralysis, and often survive the latter for some time. The affected muscles present the reaction of de- generation; there is augmentation of the galvanic and diminution of the faradic contractility. - 8 5 - The hands soon become awkward and clumsy; the patients drop or upset objects that they attempt to handle; the upper limbs are seized with tremblings. Then the muscular enfeeblement augments; the dynamometer marks only a force of 20 kilogrammes instead of 50, and the patient finally becomes so help- less as to be unable to move himself in bed, or to feed himself. Here, too, we find the same enfeeble- ment of the reflexes, the same reaction of degenera- tion, as in the lower members. The muscles of the neck and face may be para- lyzed in their turn. The paralysis of the face is rare; it may be complete or incomplete, unilateral or bi- lateral; in the latter case the features remain motion- less, and the visage takes on a stupid expression, although there may be no intellectual trouble. The tongue, the lips, the cheeks, may be affected at the same time; the saliva flows continually from the mouth; the tongue is agitated with fibrillary tremors, and may even hang out of the mouth. The patient speaks with difficulty, and stutters; can neither blow -nor whistle. En resume, the paralytic troubles may be united so as to form the labio-glosso-laryngeal syndrome. Paralysis of the bladder and rectum is also ob- served. If the muscles connected with the spinal column are affected, the latter is curved forwards, or may be deviated laterally. In the case of paralysis of the vocal cords, there is complete aphonia. — 86 — The heart troubles may be limited to temporary palpitations, tendencies to fainting, to slight irregu- larities of the pulse, but at other times take on a very grave aspect and manifest themselves by precordial anguish, cardiac ataxia, slowing of the pulse, attacks of suffocation, and syncope. Henoch divides the cardiac paralyses into three groups: (i) Early paraly- sis, whose prognosis is very unfavorable; (2) cardiac paralysis with later, but sudden, onset, coming on, so to speak, in full health, and accompanied with con- siderable frequency of the pulse; (3) cardiac paralysis developing more slowly, when there already exist other paralytic phenomena; prognosis is less un- favorable. The symptoms of respiratory and cardiac paralyses may be united and give rise to bulbar crises, indicated by Duchenne under the name of "bulbar form of diphtheritic paralysis " The patient has crises of asphyxia, finally fatal, or he may be carried off by an attack of syncope. The troubles of sensibility are very frequent in diphtheritic paralysis. Almost always they attack the paralyzed regions; often, however, we note akinesis without anaesthesia. The most frequent alteration of sensibility is anaesthesia; exceptionally there is hyper- aesthesia, which is announced in the lower limbs by numbness and formication, and generally precedes the paralysis. Frequently the anaesthesia, when it exists, does not extend above the knees or elbows, but this localization is not constant, and the anaesthesia may - 8 7 - be generalized. It is sometimes accompanied with analgesia so complete that surgeons have been able to perform cutting operations without chloroform. The anaesthesia may affect the lips, tongue, and cheeks; and in rare cases the special senses of hear- ing, smell and taste have been abolished. The speech is often hesitating, stammering. A capital fact in diphtheritic paralysis, one that distinguishes it from all other paralyses by peripheral neuritis, is that there is no muscular atrophy; the paralyzed limbs always retain their normal aspect and volume. In very rare instances the velum pendulum is not affected, and the disease is localized in one muscular group without attacking other groups or other parts; ■such are the cases where the paralysis takes on the paraplegic or hemiplegic form, or where it is limited to the eye muscles, to a forearm, a leg, the hands, the feet, the lips, the anus, or the muscles of the trunk. In the localized form the paralytic accidents may be essentially transient, and may disappear after a few days. In such cases the enfeeblement of the velum pendulum only manifests itself by a little dys- phagia; now and then a little liquid flows back through the nose, but the patient on the whole swal- lows well. This is what happens also after trache- otomy; the drinks flow back by the cannula for a day or two. The paralysis of the velum pendulum may last a — 88 — considerable time, but in general, when it remains limited, it is perilous only by the dangers of asphyxia to which it exposes the patient in the possible pas- sage of aliments into the air-tubes. When the par- alysis is generalized, its course is slow, lasting weeks or even months. Yet it is not rare to see the early paralysis disappear in a few days, to return during convalescence under a different form. Landouzy has described a form of diphtheritic paralysis whose course resembles that of the acute ascending paralysis of Landry, attacking successively the lower limbs, then the upper, as well as the muscles of the trunk, accompanied by bulbar accidents, and terminating rapidly in death without any trouble of sensibility. Some writers have regarded mobility and diffusion of the symptoms as characteristic of diphtheritic par- alyses; but though these attacks do sometimes pass from one limb to another, then return to the one first affected, such alternations are not the rule. If fre- quently the paralysis invades successively the differ- ent vital apparatus in the order which we have adopted for the symptomatic description, there is nothing fixed about it. When one organ is affected, no one can foresee which member will suffer next; nothing gives assurance as to the time that the akinesis is to remain fixed to one part, for the para- lytic phenomena sometimes present remissions and exacerbations which defy any prevision. The paralysis terminates in recovery more than eight times out of ten; in these cases, power of move- ment reappears first in the lower limbs, then in the throat, then in the upper members, the trunk, the viscera, the eye. Generally the organs paralyzed first are the first to recover. There is, however, no fixed rule even here, and it often enough happens that after having been the first affected, the velum pendulum is the last to resume its functions. When the termination is fatal, death may take place slowly, rapidly, or suddenly. If slowly, the pa- tient becomes cachectic and more and more feeble; the profound troubles from which he suffers are generally attributed to inanition, as he refuses to take food for fear of suffocation or of reflux by the nares. But it has been observed in these cases that feeding by the stomach-tube does not always suffice to save the pa- tient. The cachexia, therefore, must be referred to the diphtheritic poison. Writers have mentioned as occasionally occurring after diphtheria, nervous affections distinct from the diphtheritic paralysis: pseudo-membranous menin- gitis, of which three striking cases are on record; hemiplegia following cerebral hemorrhage; multilo- cular sclerosis; attacks of mania, of symmetrical asphyxia of the extremities, of hysterical paralysis. Lyonnet even mentions certain arthropathies of nerv- ous origin, a sort of trophic peri-articular affection supervening during convalescence from diphtheria. COMPLICATIONS DUE TO SECONDARY INFEC- TIONS. We have seen, in studying the secondary infec- tions of diphtheria from a bacteriological point of view, that the streptococcus pyogenes, often found in the false membrane associated with the Loeffler ba- cillus, may invade the circulation and infect the entire organism. It thus produces a general septicaemia which much modifies the clinical aspect of the dis- ease. Gangrene may invade the points attacked by the diphtheria. The parts subjacent to the false mem- brane soften; the latter becomes black, and gives off a fetid odor. The gangrene may extend in surface and in depth, and hasten the fatal termination. Suppurations are numerous, with multiple locali- zations; note the middle-ear otites, the glandular abscesses, the phlegmons of the neck, the perichon- drites of the larynx, the suppurations of the trachea, etc. Cutaneous suppurations, patches of impetigo, pustules of eczema, multiple whitlows, boils, frequently accompany diphtheria in children. Endocarditis is very rare; Sanne in 149 cases had not seen one with this complication. I have placed among the secondary infections the diphtheritic erythemata, because in his recent work Mussy attributes to the streptococcus their pro- duction in most cases. These erythemata resemble — 9 i — those met with in the false (streptococcus) diphthe- rias, and in puerperal fevers. (This pathogenic ex- planation demands further substantiation.) The frequency of these erythemata is variable — once in thirty cases, sometimes once in four or five cases. Adults are much more subject to them than children. They are early, appearing during the first week; or they may be late, and testify to a profound infection of the organism, to be certainly followed by death in a short time. The eruption appears in cer- tain favorite localities, about the wrists, elbows, knees, ankles, the upper part of the thighs; in general, it respects the face. Robinson describes two species of erythema appearing in the course of diphtheria; the one early, transient, apyretic, scarlatiniform, without desquama- tion; the other tardy, special to toxic diphtheria, mul- tiform, and rubeolic. Mussy describes a multiform erythema, lasting from one to four days, neither desquamative nor pru- riginous; a scarlatinifoi m non-desquamative erythema; a rubeolic erythema; and a purpuric ery hema, asso- ciated or not with a multiform erythema. Fraenkel considers the latter one of the most frequent eruptions of diphtheria. This variety may appear at the onset or at the end of the disease. It is constituted by little haemorrhagic spots whose size varies from that of a pea to that of the head of a fine pin. This erup- tion may easily pass unperceived. — 9 2 — Broncho-pneumonia may complicate all the local- izations of diphtheria, but is met most frequently in the course of croup, and especially of croup after tracheotomy. It is more frequent in the infant under four years, and more grave in the adult. When it accompanies diphtheritic angina, it is general. y be- cause we have to do with a hypertoxic form of the disease; the broncho-pneumonia is then early. In croup we observe it sometimes from the first days be- fore tracheotomy, sometimes two or three days after the operation, sometimes later still, when all danger seems to be over. In the hypertoxic diphtherias, the physical and functional signs of the broncho-pneumonia remain com- pletely masked, and the pulmonary lesion is only rec- ognized at the autopsy. In the other forms of diph- theria it is easier to recognize. But it is always necessary in children to base a diagnosis rather on the general symptoms and functional disorders than on the physical signs, which are tardy and obscure. In croup, if the broncho-pneumonia comes on after tracheotomy, the infant is pale and restless, the dyspnoea being very marked and characterized by a great frequency of the respiratory movements, with beating of the alse nasi. This is apparent when the voice is not altogether extinct, when there is no at- tack of suffocation, and the stridulous inspiration is very little accentuated. The skin is burning hot, the temperature very high. Auscultation reveals nothing — 93 — characteristic. If, however, it is thought desirable to practice tracheotomy, the operation is not followed by any relief, and the infant dies at the end of a few hours. When you perform tracheotomy, even though the broncho-pneumonia may not have already com- plicated the disease, you have still to fear lest the lung may be infected secondarily to the operation. If the respiration becomes noisy, and rises above forty or fifty per minute, if the expectoration becomes suppressed, and if the cannula becomes dry, so that the air produces in passing through it a peculiar whizzing sound, you may be sure of a broncho-pul- monary complication. At the same time the wound becomes grayish, and soon expectoration is reestab- lished, and the cannula gives vent to a puriform sanies which blackens it. The temperature, which usually falls two or three days after the operation, remains about 40 C. The pulse is more than 150 per minute. Auscultation still gives very doubtful results. The blowing cannula-sound masks or modifies the pulmonary signs; you may, however, distinguish large mucous rales and sometimes a souffle. When the broncho- pneumonia is tardy, it comes on at a period when the patient seems to be out of danger. The later its onset, as a rule, the more favor- able the prognosis; it is always, however, a very grave complication, and kills nine times out of ten. Erysipelas is a very rare complication in diph- — 94 — theria, apart from croup and tracheotomy. Some- times it supervenes after the latter; you will then see the red, tumefied borders of the wound so character- istic of this complication. The lips of the tracheotomy wound then become dry, take on a palish-blue tint, and retract; the redness and swelling extend to the neck, face, and whole body. The general state now becomes worse, the temperature suddenly rises, and with the extension of the erysipelas the patient be- comes restless, delirious, and irremediably comatose. Measles sometimes complicates diphtheria, es- pecially in children's hospitals, where it has such op- portunities to spread. This exanthem is more likely to attend croup, and especially after tracheotomy. The invasion of the diphtheria is announced by an arrest in the cicatrization of the wound, and by high fever. From the first few days a broncho-pneumonia is present, which carries off two-thirds of the patients. Scarlatina complicates diphtheria much more rarely than does measles. I saw it prevail as an epi- demic in August, 1889, in a barrack hospital, among diphtheritic patients there quarantined, when it proved very fatal. The onset is announced by high fever, soon followed by the characteristic eruption. Whooping-cough is a rare complication of croup. The paroxysms do not increase by the attacks of suffocation, but broncho-pneumonia soon sets in, with all its dangers. CLINICAL FORMS. We may, with Trousseau, admit three forms of diphtheria: the simple or benign, the infectious, and the form that is toxic at the start. This division cor- responds sufficiently well with clinical observation. i. Benign diphtheria generally appears under the form of sore throat, but sometimes attacks pri- marily the larynx, and we have then croup from the start. The disease announces itself by a slight fever, prostration, and malaise. When angina is the primary manifestation, there will be redness and swelling of the tonsils — often of only one. Over the swollen tonsils a white exudate forms, well circum- scribed, semi-transparent, which rapidly thickens and thus constitutes a loosely adherent false membrane. Sometimes, instead of forming a patch covering a part of the tonsil, the membrane develops by lenticu- lar points well separated, resembling herpes of the throat. An eruption of herpes on the lips may in- crease still more the difficulties of diagnosis. Gland- ular enlargement is the rule, but has, perhaps, less importance than Trousseau assigned to it. The false membrane remains localized to the throat except in rare cases, where it gains the larynx and constitutes a purely mechanical danger; but the disease remains benign, and, if it is possible to avoid asphyxia, re- covery is not delayed. These benign manifestations of diphtheria are of - 96 - short duration; recovery follows at the end of six or eight days. Albuminuria is generally lacking; par- alysis sometimes appears, however, during conva- lescence. However slight the disease seems, and however inconspicuous the blood-poisoning, these benign forms are able to transmit grave diphtheria. This is the first argument to advance to those who are unwilling to recognize diphtheria in these light manifestations. The second argument is furnished by bacteriology, which has revealed the presence of the bacillus of Loeffler in all its virulence in these false membranes, so little inclined to invade the sur- rounding parts. Furthermore, there exist abortive cases, in which the local symptoms are almost imperceptible, amount- ing only to a simple redness of the throat; the false membrane is insignificant or absent. Nevertheless these cases are met with in times of epidemics by the side of the malign forms; their origin is the same, and they may, in their turn, give rise to malignant diph- theria. We must also add that these abortive cases, with local manifestations almost nil, may in some cases develop general symptoms of extreme gravity. 2. Infectious diphtheria generally establishes its primary focus in the throat; it may, however, first ap- pear on other mucous surfaces or even on the skin. The general condition may be the same at the onset as in the benign form, but as a rule the fever is quite high. The aspect is one of extreme depression. The counten- — 97 — ance has a pale, leaden hue; the mucous membranes are cyanosed. The intelligence is intact during the en- tire disease, but the general prostration is pronounced. What specially characterizes this form is the capital importance belonging to the local symptoms: the false membrane is essentially invasive; it spreads largely over the tonsils, the soft palate and uvula, gains the nasal fossae, the larynx, the bronchi, the lips, the con- junctivae, the genital organs, and covers the surface of blisters, wounds, and spots of impetigo. In the gravest cases it takes on a dark-grayish color with gangrenous appearance; the odor is fetid; the gland- ular swelling is very marked. In the less severe cases, there is always generalization of the false membranes, but without the gangrenous aspect ; and the adenopathy is very moderate. Lastly, in certain cases, the disease for several days has the appearance of a benign diph- theria well localized; then suddenly it takes on an invading course, and spreads in less than twenty-four hours to the nasal fossae, the larynx, and the bronchi. The albuminuria, more frequent than in the first form, is not constant; but the croup and the pulmonary complications are here the rule, and constitute all the gravity of the infectious form. Death is a frequent termination. During convalescence, diphtheritic par- alysis frequently supervenes. The progress is slow; the disease lasts generally from ten to twelve days, sometimes a month; in cer- tain exceptional cases the patient continues to cough out false membranes for several months (the chronic diphtheria of Barthez). 3. In the toxic form the danger is no longer con- fined to the localization of the false membrane and its rapid invading tendency; the exudation plays only- an insignificant part compared with the profound and rapid intoxication of the organism. The accidents may assume a fulminant form, with intense fever and rapid collapse, the productioa of false membranes being variable, but glandular' engorgement excessive with infiltration of the neigh- boring cellular tissue; the patient in a few hours falls into a typhoid state, which terminates in death in the- course of twenty-four to seventy-two hours. But the disease generally lasts rather longer. The false membranes easily spread from the original focus in the throat, and take on a gangrenous aspect and fetid odor, the underlying mucosa bleeding at the least touch. Haemorrhages are the rule— from- the nose, mouth, anus, urethra, sometimes even from the stomach and bladder. Albuminuria is constant. The glands are extremely swollen. The pulse is rapid and becomes filiform; the extremities are cold; the temperature of the body is below the normal; the patient lies in a state of somnolence very like coma. Death is certain, and generally occurs before the end of the first week. Sometimes the evolution of the toxic diphtheria is quite insidious; the false membranes are of little — 99 — extent, have no tendency to invade, and often disap- pear at the end of five or six days. But from the onset the glandular swelling is enormous, the pulse is wretched, the face livid; then as the local symptoms improve, the prostration augments, the pulse be- comes feebler, the skin cold, and the patient suc- cumbs. In ambulatory toxic diphtherias the local lesions and the fever are without importance; the patient keeps up and is able to walk; but the paleness of the face and swelling of the neck cause the physician to be watchful from the onset. These diphtherias ter- minate unexpectedly in sudden death, or they may end in an unforeseen manner in the terminal accidents of the collapse. Forms Differentiated by Bacteriology. — Loeffler's bacillus being recognized as the specific agent of diphtheria, it was but natural that efforts should be made to harmonize the different clinical aspects of the disease with the results yielded by bacteriological examination of the false membrane; in other words, to ascertain if the Loeffler bacillus suffices of itself to explain the entire symptomatic tableau of diphtheria, or if in some cases there is not warrant for attributing a part or the majority of the symptoms to associated pathogenic microbes. Grancher has attempted this division, and has proposed the name "toxic forms of diphtheria" for those cases in which the Loeffler ba- cillus is alone operative, as distinguished from the "infectious form" in which the clinical picture is completely modified by the secondary infections. From a symptomatic point of view, we shall see that these two forms are quite different from those which bear the same name in Trousseau's classifica- tion. Barbier has attempted to justify the division pro- posed by Grancher, and has studied quite specially the influence of the streptococcus pyogenes, so often noticed in the false membrane, on the course of diph- theria. He admits, first, a pure diphtheritic angina (toxic angina of Grancher), due to the Loeffler bacil- lus and to it alone. These are the principal charac- ters: sore throat often nil (this first phase of the dis- ease may be latent and pass unperceived); there may be no fever, headache, or backache; the child is in not quite its usual good spirits, a little cross, and this is all; on examining the throat, typical white false-membranes, more or less easily lifted in flakes, are seen, but the mucosa is almost normal, neither red nor swollen; adenopathy absent or scarcely apprecia- ble. Propagation to the larynx is frequent, and the symptoms of this may be the first to indicate the proper diagnosis. The future of these patients, if the type remains pure, is equally characteristic. It is in them that we witness the bronchial diphtheria, with expulsion by the cannula of pseudo-membranous casts, which latter often lead to fatal asphyxia. They have coryza, but it is diphtheritic in every aspect, with closure of the nasal passages and obstructed mucous discharge. The false membrane, by hindering the entrance of air, determines the respiratory impedi- ment or arrest by the nares. The cannula at no time gives vent to pus or muco-pus; it is dry. Death re- sults from asphyxia pure and simple, or possibly from the nervous accidents — syncope, paralysis — or sys- temic intoxication. If recovery follows, the patients retain an anaemia more or less marked, and remain exposed to nervous accidents of paralytic nature during convalescence. M. Barbier then considers the phenomena which belong to the association of the diphtheria bacillus with the streptococcus as shown by bacteriologioal examination. In these cases the streptococcus has been found, not only in the throat, but also in the viscera and in the blood, and all the complications were either certainly or probably of streptococcus ori- gin. The following description shows how this micro- bian association manifests itself clinically, giving rise to the streptococcus form of diphtheria, one of the varieties of the "infectious form" of Grancher: "Typical external aspect of face and neck: Face pale, swollen or cyanosed, leaden hue; skin shiny and sometimes rosy red around the nose and on the nose itself; redness and excoriation of the upper lip beneath the nostrils; mouth open, breath horribly fetid when the bacteria of putrefaction have invaded the exu- dates, which is not rare; the act of swallowing is very painful; the patient refuses nourishment; throat much tumefied, the mucous membrane red, sanious, bleeding, swollen; false membranes often dissociated and absent, or even thick and flabby, putrilaginous; neck enor- mously swollen, owing to the tumefaction of the glands, which are, as it were, buried in an cedematous infiltra- tion of the cellular tissue of the neck; abundant nasal discharge, sero-fibrinous, sero-sanguineous, color of tobacco-juice, or even completely hemorrhagic— so great is the abundance that sometimes the liquid flows by drops. The disease often kills in the course of twenty-four hours; if the patient lives longer, compli- cations due to the streptococcus appear. The pros- tration of the patient, or oftener the extreme agita- tion, the high fever, sometimes convulsions at the end, are the principal general phenomena observed. Re- covery is rare in the infectious forms; convalesencc protracted. The throat, nose, and the outer border of the nose, long remain red and excoriated; grayish ulcerations, locally painful, are seen in the throat, and in certain cases actual losses of substance affecting the pillars of the fauces and the soft palate occur. Later complications, such as suppurative adenites, phleg- mons, etc., may still retard the recovery and even produce death." This attempt at classification of the clinical forms of diphtheria is interesting, though necessarily incom- plete, and it indicates well the way to take in order to complete our knowledge of the characters so varied — 103 — -and so dissimilar which diphtheria may present. There remains still to be studied the action on the economy of the micro-organisms of the false mem- branes other than the streptococcus, and to group together a great number of facts well studied in order to fix definitely these different aspects which the microbian associations impress upon diphtheria. Quite recently, Martin has reported cases which seem to show that the bacillus of diphtheria, associated with a coccus which often appears as a diplococcus capable of forming abundant colonies on serum, which bear a marked resemblance to those of the Loeffler bacillus, gives rise to a quite benign form of diphthe- ritic angina; while the association of the staphylococ- cus albus with the specific bacillus implies a prognosis much more grave. DIPHTHERIA IN ADULTS. Diphtheria is quite rare in adults; when it does occur, it is generally more grave than in children. Very benign epidemics among adults have, however, been reported. And in cases where the toxine of diphtheria spares the patient, respiratory complica- tions of a grave, often fatal, character, are liable to supervene. The aspect of croup in the adult is dif- ferent from what it is in the child; the glottis being large, the false membranes very seldom become suf- ficiently developed to completely occlude it and pre- vent the entrance of air. Moreover, the false mem- branes hardly ever remain limited to the laryngeal cavity; the laryngitis is accompanied by pseudo- membranous tracheo-bronchitis. Croup in the adult has a progressive course; it does not pass through the three very distinct periods observed in this disease in children. The voice, which almost always escapes complete extinction, may remain normal till death, although the vocal cords are covered with false membranes. The dysp- noea is progressive, without attacks of intercurrent suffocation. Death by progressive asphyxia is the rule; it comes on tardily, on the average at the end of two or three weeks. The concomitant manifesta- tions along the entire bronchial tree easily explain why tracheotomy is of so little relief to the adult. At the same time this operation should not be neglected — i°5 — in cases of threatened asphyxia, for instances of cure due to tracheotomy are on record. Very often in the adult, diphtheria takes the hypertoxic form. The patients are overwhelmed from the onset. The extremities are cold; the pulse small, irregular; the face pale, of a leaden hue; the breath fetid. A yellowish serosity flows by the nasal fossse, of sickening odor. The patients are also enfeebled by an incessant diarrhoea. The throat is lined with thick, putrilaginous false-membranes, and when these are removed a bleeding surface is left behind. The blood mixes with the exudate and colors it; the mucous membrane itself takes on a darkish hue, as if gangrenous. The submaxillary glands are very much engorged and painful, the surrounding cellular tissue infiltrated, and the entire neck tumefied. If the air-passages are invaded, the symptoms of croup are scarcely apparent; the dyspnoea and the cough are so little marked as hardly to attract atten- tion to the larynx. The patients die of the blood- poisoning rather than by asphyxia. We know with certainty that the form of puer- peral infection called diphtheritic, accompanied by false membranes on the vulva and vagina, is not due to the Loefner bacillus. True diphtheria is very rare during pregnancy. SECONDARY DIPHTHERIAS. When diphtheria supervenes in the course of an- other disease, it generally takes on a very marked character of malignancy, and localizes itself especially on the organs which are attacked by the primary dis- ease. Its course is rapid, especially when it leads to death. Diphtheria may complicate all diseases: tuberculosis, typhoid fever, pneumonia, etc. It is less often a complication of scarlet fever than has been supposed. It very exceptionally attends the onset of scarlatina, for the pseudo-membranous angina of this period is seldom of diphtheritic nature. On the other hand, the pseudomembranous anginas which super- vene at a late period (the second week) are almost always manifestations, of diphtheria; the scarlatina, after a normal course of a few days, has disappeared as well as the initial angina, the temperature has fallen to the normal, desquamation has already set in, when unexpectedly the general condition becomes aggravated, the child grows pale, the fever kindles up, and the glands of the neck become engorged. On examining the throat, we find it filled with grayish false-membranes. Patients affected with these late anginas generally succumb rapidly with all the symp- toms of diphtheritic poisoning. Diphtheria following measles is also of extreme gravity. Under two years, death is almost certain; patients die of infection or of broncho-pneumonia. — 107 — Diphtheria is very rarely a complication of whooping-cough, appearing chiefly during the spas- modic period. The paroxysms of coughing may then act favorably in aiding the expulsion of the false membranes. According to Vaquer, the toxic form is rarely observed, but broncho-pneumonia is always to be dreaded. It will not do to hesitate to practice tracheotomy when indicated, for this operation has saved a number of lives. Diphtheria secondary to typhoid fever and small- pox terminates fatally in a few days. As a complica- tion of typhoid fever it rarely assumes a form other than the hypertoxic. PROGRESS— DURATION— TERMINATION. When studying the clinical forms of diphtheria, we saw that this disease was complex, and that it would be impossible to include a satisfactory account of its course in one description. In one case, for example, diphtheria appears in a benign form, remains local and circumscribed, occa- sions a little fever for a few days; the false mem- branes hardly re-form, soon disappear, leaving a little redness of the mucosa. All the symptoms disap- pear in about a week; the patient, however, remains for some time pale and feeble, and has a slow conva- lescence. Again, the production of the false membrane is exuberant and becomes a real danger. It spreads rapidly, invades new surfaces, and when removed is reproduced; the general condition is not bad, but the exudation may at any moment obstruct the air- passages, and then asphyxia is imminent. This form sometimes lasts a fortnight, sometimes a month. Take another case: The patient is unconscious, his countenance livid, neck and face much swollen, respiration panting and becoming extinct. Profound systemic intoxication is present. It often requires an attentive examination to find the false membrane which is the origin of all the evil. In the course of five or six days, sometimes in twenty-four hours, the diphtheria has invaded the entire organism. By these examples it is apparent how variable is — 109 — the course of the disease. At the same time, when the false membrane does not remain absolutely local- ized at the point of primary infection, the process of invasion follows a sufficiently regular course: you see the membrane spread to the throat, nasal fossae, larynx, trachea, bronchi, etc. If the law of Breton- neau and of Trousseau, thus formulated: "The propagation takes place in an invariable order from the upper parts to the lower " — if this law is not absolute, it nevertheless indicates how completely these two observers had recognized a sort of auto- inoculation, of successive contamination of the parts below by a liquid secreted by the false membrane above. Evidently the contagion may spread upward as well as downward, as in cases where it passes from the pharynx to the Eustachian tube, and from the nose into the nasal duct; but we must not forget that there are also instances where the contagion is carried by the fingers of the patient or those of his attendant. But these facts are not sufficient to invalidate the law of Bretonneau, which finds justification in practice. Diphtheria usually runs its course in from two or three days to a month. There are exceptional cases where the diphtheria becomes chronic and the patient con- tinues to expel false membranes after two or three months. Death is the termination of diphtheria in more than two-thirds of the cases; it may supervene sud- denly during the first two or three days of the disease. Sometimes it terminates the hypertoxic anginas with fulminant development, the patient succumbing to a veritable hyperacute septicaemia. Then again, in diph- theria which has early invaded the air-passages, in a few days menacing asphyxiating symptoms appear; this is the strangulator)' diphtheria, against which trache- otomy remains powerless if there be pseudo-membra- nous bronchitis, or if the diphtheria be complicated with broncho-pneumonia. Sometimes the patient suc- cumbs to the early cardiac paralysis first mentioned by Henoch. During the stationary period (fastigium), croup and broncho-pneumonia are ^likely to carry off the patient more or less rapidly. When there are no diphtheritic manifestations in the air-passages, the disease may terminate slowly by a progressive ca- chexia, due either to the nature of the intoxication or to the disorders produced by secondary infections, such as gangrene, phlegmons of the neck and groin, mediastinitis, erysipelas, or an intercurrent eruptive fever. Even in convalescence, all danger is not past; an acute myocarditis, passing from latency to activity, may cause sudden death. Rapid asphyxia is always imminent when the respiratory muscles become para- lyzed; this frequently happens as a sequel in diph- theritic paralysis. Sudden syncope follows a crisis of .bulbar or cardiac paralysis. In full convalescence, broncho-pneumonia may attack a patient and carry him off. Recovery very often follows the simple forms of diphtheria. Unfortunately these are far from being most frequent. Not all patients succumb to those invasive diphtherias which constitute the " in- fectious form " of Trousseau; some of them will re- sist croup, tracheotomy, broncho-pneumonia, the paralysis of convalescence. But the toxic or hyper- toxic form is always fatal. Recovery is announced by the progressive dis- appearance of the false membranes, which reappear more and more slowly; the adenopathies diminish, the general state improves, and after a convalescence always rather slow, complete restoration comes about. A first attack confers no immunity from future attacks; the patient is subject to relapses and recur- rences. It is not rare to see the false membranes re- appear several days after the advent of convalescence. There is nothing surprising about this, for we know that the bacillus with all its virulence lives in the mouth for some time after the false membranes have completely disappeared. I have seen croup follow recovery from a benign diphtheritic angina. Often the second attack of diphtheria is more benign than the first, but there are numerous exceptions to this rule. Relapses may be occasioned by eruptive fevers, such as measles or scarlet fever. Single recurrences of diphtheria have been frequently noted, and in some cases even multiple recurrences. PROGNOSIS. When the false membrane remains localized and shows little tendency to spread and to be reproduced, the air-passages remaining free and the neighboring glands being little affected, the general state good, and little or no albuminuria, there is reason to regard the disease as benign and to hope for a favorable termination. But the diphtheria none the less re- mains a grave disease, for even in these cases, so \ght in appearance, there is always danger of late croup, a myocarditis, or a paralysis during conva- lescence. Diphtheria comprehends three factors of gravity: the patient, the disease, and the environment. Diphtheria is particularly grave in the infant and in the adult. Before the third year of life it is almost always fatal. The previous health of the patient is also a mat- ter of importance. Lymphatic or scrofulous subjects appear to present a favorable soil for grave infec- tions. The malignancy of secondary diphtherias we have already discussed. The course of the disease may be influenced in a capital manner by the degree of localization of the diphtheritic infection, by the extent of systemic in- toxication, and by the nature of the infectious com- plications. The rapid extension of the false membranes to — H3 — the nasal fossse, the larynx, and the bronchi, is of special gravity by reason of the mechanical troubles it occasions. As for the pseudo-membranous coryza, it is always of bad prognosis, for it indicates the in- tensity of the infection. Often the quite special viru- lence of the bacillus is already announced locally by the putrilaginous, sometimes gangrenous, appearance of the false membranes. The poison soon makes its action felt on the en- tire organism. The glandular engorgement, the pallor of the visage, the prostration, the haemorrhages of the first few days, especially that constant oozing from the mouth and throat which we so much dread to see, are precious elements of prognosis; the fever and albuminuria are much less important. But the intoxication may be slow and insidious, suddenly manifesting itself in convalescence by a myocarditis or paralysis. It is at the advent of con- valescence that it is necessary particularly to watch the heart, whose most profound lesions announce themselves only by troubles trifling in appearance — a little precordial distress, palpitations, lipothymia. Likewise, a paralysis which begins by an insignificant difficulty of deglutition may become rapidly general and carry off the patient in a few days. Secondary infections may determine veritable septicaemias, at the same time that they aggravate the virulence of the diphtheria bacillus; the extreme pallor of the countenance, the deformation of the in- — ii 4 — filtrated neck, the yellowish, sanious and fetid dis- charge from the nares, the agitation or the somno- lence, the general enfeeblement, leave no doubt as to the issue of the disease. The gangrene which may complicate the diph- theria testifies less to the dilapidation of the patient's organism than to the gravity of the disease itself. It is nevertheless of serious prognosis. There is general agreement that the infectious erythemata which supervene at the onset of diph- theria have no influence on the course of the disease. It is not so with the late erythematous rashes, which are almost always precursors of death. Broncho-pneumonia is one of the most grave complications of diphtheria. We have seen how little we can depend upon the physical signs in making a diagnosis. It is chiefly the coincidence of a very high elevation of temperature with a marked and growing dyspnoea that will help the practitioner to recognize this affection, which is so very fatal. Bad hygienic conditions, close, ill ventilated rooms, overcrowding, want of cleanliness or of nour- ishment, are unfavorable circumstances. The danger is of course greater in certain epi- demics of peculiar malignancy; diphtheria is also espe- cially fatal in large cities. It is generally very malig- nant in winter and in the spring time, in cold and damp seasons, and in certain northern countries such as Sweden, Norway, Denmark, and Northern Ger- many. DIAGNOSIS. The elements which contribute to the diagnosis of diphtheria are not all of equal importance. The principal one, undoubtedly, is the false membrane — a fibrinous exudation, of whitish or grayish color, quite adherent to the parts beneath, forming when removed a coherent lamina insoluble in water, and reproduced in the throat after ablation. Angina being the most frequent manifestation of diphtheria, the presence of a pseudo-membranous exudation on the tonsils is very significant, especially when it spreads to the soft palate and the uvula. The engorgement of the glands corresponding to the region invaded by the false membrane, the pallor, the general enfeeblement of the patient, the albumin- uria, may also give valuable indications. The paraly- sis during convalescence, even, by its special behavior and evolution, is enough sometimes to warrant a retro- spective diagnosis when every other manifestation of the diphtheria has d ; sappeared. But these characteristic symptoms are not always very apparent. In very young children, particularly, the disease is frequently overlooked by reason of inattention to the throat. Trousseau with good rea- son advises to examine the throat in every case of ill- defined infantile sickness. Every one of the elements of diagnosis above mentioned may be wanting. Anginas without false — n6 — membranes have been observed in the course of cer- tain epidemics. They alternate with the ps udo membranous manifestations, are contracted by con- tact with an undoubted case of diphtheria, and trans- mit an angina with characteristic exudation. But these "diphtherias without diphtheria" tre too excep- tional to occupy us long. On the other hand, it is not rare to see the false membrane appear discrete and become detached in a day's time or less, and not again be reproduced; nor need the ephemeral nature of the characteristic local symptoms have any influ- ence on the evolution of the disease. In other cases, and especially in he benign forms, the glandular en- gorgement is wanting; the general condition may remain good; the albuminuria may be absent. An eruption of herpes on the lips or nares is not a symp- tom of much significance, for it may coincide with genuine diphtheria as well as with herpetic angina. The diagnosis of acute diphtheritic myocarditis is very difficult. In the young child who in full con- valescence is suddenly carried off by a syncope, the cause of the terminal accident is very difficult to de- termine and to distinguish from a cardiac paralysis, if the medical attendant has not previously noted an extreme feebleness of the pulse accompanied by cardiac intermittences. In the adult the symptoms evolve less rapidly; first a praecordial anguish, then cardiac excitation, soon followed by feebleness of the organ with irregularity and softness of the pulse, — ii 7 — dyspnoea, collapse, and repeated syncope. Unhappily, these symptoms may accompany pleuro-pneumonia or pericardiac complications, which must first be eliminated by an attentive examination before the physician can decide that he has an acute myocarditis to deal with. The diphtheritic paralysis is generally easy to recognize, especially when account has been taken of the manifestations of diphtheria which have preceded it. In the exceptional cases, where the paralysis re- mains localized to the lower members without having ever affected any other part, it is distinguished from certain peripheral neuritic paralyses, and particu- larly from alcoholic paraplegia, by the absence of pain and especially of muscular atrophy. If it sometimes has a superficial resemblance to general paralysis, glosso-labio-laryngeal paralysis, multilocular sclerosis, or locomotor ataxia, it is sufficient to bear in mind its history and peculiar signs in order to avoid any confusion. We have already seen of how little help are the physical signs in enabling one to decide as to the in- vasion of broncho-pneumonia in the course of diph- theria. A high fever, a marked and continuous dysp- noea, with beating of the alse nasi, even when there are little or no paroxysms of suffocation or of wheez- ing, are symptoms quite as precious as those furnished by auscultation and percussion. Thrush rarely resembles diphtheria. It may, however, extend to the throat, and even localize itself there exclusively, so as to cause doubt in the mind of the attending physician. The constitution of its grumous coating should dissipate these doubts. Moreover, if you take a little of the thrush membrane, crush it on a glass slide, and treat it with potassa, you will see under the microscope the mycelium and spores of Oidium albicans. When diphtheria passes from the throat to the larynx, one is warned of the laryngeal nature of the lesion by noting the patches in the throat. But in cases of primitive croup or where the patches in the throat have disappeared, the diphtheria reveals itself only by the mechanical obstacle which it opposes to the respiratory functions. Now in the infant the affections which cause similar symptoms are numer- ous, by reason of the small diameter of the glottis. There is only one sign pathognomonic of diphtheria exclusively localized in the larynx, namely, the ex- pectoration of a false membrane, and this is often wanting. In laryngismus stridulus, the first access of suffo- cation comes on suddenly in the night; the patient may have had only a little cold in the head or a little hoarseness during the day, perhaps no abnormal symp- toms whatever. In the interval of the paroxysms the voice is rarely altered, and the cough is resonant, the respiration calm; while in croup the voice and the cough are rapidly and completely extinguished, the — II 9 — •dyspnoea becoming more intense as the paroxysms are repeated, and never presenting complete remis- sion. Retro-pharyngeal abscess or oedema of the glot- tis may also narrow the glottic orifice so as to give rise to symptoms of asphyxia very like those of croup. It will not do to neglect exploration of the pharynx and upper part of the larynx with the finger introduced into the throat, before pronouncing on the nature of the disease. The differentiation of the false diphtherias will be considered on the next page. FALSE DIPHTHERIAS. The affections just enumerated resemble diph- theria more or less, but it is almost always possible to differentiate them objectively. It is not so with the diseases we are about to study; they reproduce com- pletely the clinical picture of diphtheria, and differ only by their course and prognosis. Often a bacteriological examination is absolutely necessary, to remove doubts. In a scarlatinous patient who in the first two or three days of the disease has had an erythematous angina, possibly accompanied by a pultaceous deposit, the aspect of the throat will be modified on the second or third day of the eruption, and thick lenticular points are visible at the orifice of the tonsillar crypts; these points soon run together and form a creamy coat with a pultaceous aspect, but with little power of resistance. The next day there is a firm, coherent false-membrane, which may be removed in large flakes. This pseudo-membrane invades the uvula and soft palate, and may spread to the pharynx. Very white at first, it soon becomes grayish or yel- lowish; may be strewn with black patches, the result of little haemorrhages. The pseudo-membranous de- posit is very adherent to the mucosa, and reproduces itself after ablation. Often, when it is removed, the mucous membrane underneath bleeds and shows an eroded, ragged, sloughy, indented surface. The dys- phagia and sniffling are pronounced. There is accom- panying this bad condition of the throat, engorgement of the submaxillary glands. The temperature is high. According to the degree of extension of the false membranes, the gravity of the general symptoms, and the amount of general infection attributable to the angina, we may distinguish three forms of this sore throat: In the benign form the false membranes are very limited and have but little tendency to spread; the neighboring glands are only slightly swollen; the general condition is good, and the fever lasts but a short time; no complication sets in as a consequence of the angina; the false membranes may early invade the tonsils and uvula, tut have little tendency to re-form, and rapidly disappear; the angina causes no general symptoms. — The grave form is characterized not only by the rapid extension of the false mem- branes, by their persistence, and by the intensity of the submaxillary engorgement, but also by the long duration of the angina, which, in the cases which I have observed, has lasted from nine to twenty-three days; the fever and general symptoms are prolonged, and there are almost always complications, such as broncho-pneumonia, nephritis, rheumatism, otitis, im- petigo, etc.; this form does not of itself cause death, but it makes the prognosis doubtful by the com- plications which it entails. — If in the forms before mentioned, the symptoms independent of the angina are the most noteworthy, it is not so in the scarlatinal septic form; an atypical, fugacious eruption, scarcely visible, characterizes this variety; the other symptoms depend only on the angina, which seems of itself to constitute the whole malady, hence the name of scar- latina anginosa which is often given it. The most complete descriptions of hypertoxic diphtheritic an- gina give a faithful portraiture of the septic angina of scarlet fever. I have proved the existence of these different forms by numerous bacteriological examinations. By the process of sowing in striae on gelatinized serum and gelose, I have made bacteriological examination of nineteen cases of pseudo-membranous angina at the onset of scarlatina. Only one of these anginas was of diphtheritic nature; in the eighteen other cases not a single colony of the Loeffler bacillus could be found, but the presence of the streptococcus pyogenes was constant in the false membrane. It is to-day settled that pseudo-membranous angina at the onset of scarlet fever is almost never of diphtheritic nature; this affirmation is based on forty-five cases in which bacteriological examination was made with all the rigor possible. On the other hand, the pseudo-membranous angina which comes on at a late date in scarlet fever is almost always true diphtheria. In five out of six cases examined by Loeffler, Morel, and myself, the Loeffler bacillus was found, the sixth case being a streptococcus diphtheria, in which the patches did not appear till the twenty- seventh day, during convalescence. We know there is a form of puerperal infection improperly denominated " puerperal diphtheria," in which true fibrinous false-membranes are found on the vulva, vagina, mucosa of the uterus and tubes, and even on the serous membranes. Suppurations are often among the symptoms. This fibrinous exu- dation presents characters very similar to those of diphtheritic membranes; but M. Widal has sufficiently differentiated them by showing that while the patches of diphtheria are due to the Loeffler bacillus, those of puerperal infection are the product of the strepto- coccus pyogenes. It is not rare to note in syphilitic patients, some- times on the surface of an infectant chancre, oftener on secondary syphilides, a thick, grayish, adherent false-membrane very like the diphtheritic exudate. When it forms only a simple grayish film, we have the opaline papule; when thicker, lamelliform, opaque, of a dull white color, it is the porcelain-papule of Four- nier. It is in general on the genital organs of the female that we observe syphilitic lesions thus covered with false membranes; they may also be met in the throat, and strikingly resemble diphtheritic angina, for which they have been frequently mistaken. The onset of these diphtheroid anginas of syphilis is ac- companied with engorgement of the submaxillary glands and with general symptoms often very marked: malaise, chills, cephalalgia, fever, pale and earthy hue of countenance. — I2 4 — The clinical signs which enable us to differentiate the pseudo-membranous syphilides from diphtheria are not constant. The objective characters of the false membranes are the same in both affections. At the same time, in most cases the diphtheritic patch may readily be detached with a swab, while the syphilitic exudate resists a mere rub. The subjacent mucosa is almost always intact in diphtheria; whereas it bleeds easily and almost always presents ulcerations when the false membrane is syphilitic. When true diphtheria spreads, it easily reaches the posterior pharynx and trachea; the diphtheroid syphilide gen- erally respects the larynx, and does not spread be- yond the anterior pillars of the soft palate. In syphilis, false membranes may be present on the hard palate, while this localization is exceptional in diph- theria. The pallor, the general prostration, the pres- ence of albumen in the urine, are symptoms which pertain rather to diphtheria than to syphilis. The recognition of syphilitic antecedents, and especially the detection of concomitant secondary syphilides, plead in favor of syphilis. So much for the differ- ential diagnosis of these two pseudo-membranous affections. Roux and Yersin have noted several cases of primary pseudo-membranous angina which were not of diphtheritic nature. Menetrier reports a case in which he isolated the pneumococcus. Netter has also noticed the presence of the pneumococcus in — i25 — laryngeal false-membranes- when there was no Loef- fler bacillus present. In two cases which I personally- studied in 1890, and which were tabulated as false diphtheria, both occurring in our hospitals, the pseudo- membranes did not contain the LoefHer bacillus, but gave fine cultures of the streptococcus pyogenes. Net- ter has also noted a case of diphtheroid angina due to streptococci and staphylococci. Baginsky, out of ninety-three cases of apparent diphtheria, found sixty-eight due to the Loeffler bacillus, and fifteen to staphylococci and streptococci. Examples of these false diphtherias have been given by Morel, Mussy, and Martin. If most of these cases behave clinically like be- nign diphtheria, sometimes these false diphtherias are accompanied by grave general symptoms, such as infectious erythema, and great engorgement of the glands, and end in death. PATHOLOGICAL ANATOMY. We have to study successively the lesions pro- voked by the diphtheritic bacillus, those which are due to the action of the toxine produced by the bacil- lus, and those which result irom the secondary infec- tions supervening in the course of the diphtheria. i. Lesions Due to the Diphtheria Bacillus.— We have seen that the diphtheria bacillus produces but one lesion, the false membrane. We have already studied the physical characters and the various local- izations of the false membranes in the regions acces- sible to view. When at the autopsy we inspect the false membranes which have invaded the air-passages — larynx, trachea, and bronchi — we see that they have taken the form of these organs; they line them continuously or in patches. We meet them princi- pally at the base of the epiglottis, on the aryteno- epiglottidean ligaments, on the upper surface of the vocal cords, etc. In the trachea, they line chiefly the posterior wall. They may also be found in the sinuses of the face, the Eustachian tube, and the middle ear, to the walls of which they are moulded. It is very rare to observe them in the digestive tube. In the oesophagus they become elongated into bands lining the organ to some depth, or into cylinders more or less elongated. In the stomach they form very thin patches or rings around the cardia or pylorus. In the intestine they spread out in patches or form cylindrical moulds of the gut. — I2 7 — From a chemical point of view, a false membrane is composed of the following elements: fibrin, an amorphous substance, mucin, and fatty matters. A more interesting study because of its practical con- sequences is that of the action of chemical agents on the exudation. Very few acids have more than a slight action upon it; the mineral acids and acetic acid cannot dissolve it; it is, however, soluble in citric and especially in lactic acid. False membrane left in a 5-per-cent. solution of lactic acid dissolves in a few minutes. The same result takes place with the alkalies, potassa, soda, and lime. Lime-water has as rapid an action as lactic acid; and we may obtain still better results with a solution of caustic soda in glycerin. Bretonnean was the first to establish the fibrinous nature of the false membrane, and to show that it is not constituted by an eschar of the subjacent mucosa. Since then, pathologists have explained the formation and constitution of the diphtheritic membrane in two ways: some hold that it is a fibrinous exudation, others that it is a special transformation of the epithe- lium of the mucosa. The first view is supported by the French school — by Bretonneau, Trousseau, Laboulbene, Robin — who regard the pseudo- membrane as an exudation of fibrin which in its coagulation imprisons epithelial elements, fatty matters, and various products of in- flammation. The second theory is that of the Ger- 128 man school, first stated by Virchow, and subsequently developed by Wagner. The latter describes the formation of the false membranes in the pharynx by a process beginning with the development of a clear, homogeneous reticulum, the meshes of which contain lymphoid cells; this reticulum being directly derived from a particular metamorphosis of the pavement epithelia. The latter swell; little, clear, round-oval spaces develop around the nucleus, and increase in size while deforming the cell. At the same time the protoplasm resists further destructive agencies, and resembles fibrin by its chemical composition, while its nucleus disappears. The deformation of the cellu- lar protoplasm becomes more and more marked; it elongates and forms filaments, which ramify in every direction, and, joining those which issue from neigh- boring cells, form with them a continuous network. The most superficial cells of the epithelial layer do not participate in these alterations. Below the glottis and in the trachea the exudation has still an epithelial origin, but as the epithelium is cylindrical the reticu- lum is closer. Wagner admits that this transforma- tion of the cylindrical cells is much more difficult to see. According to Leloir, we are to seek for a true conception in a sort of eclecticism — the epithelial alteration constituting, as he believes, a stage of onset, the fibrinous exudation corresponding to a more advanced stage. During the catarrhal period — i2 9 — of the diphtheritic angina, when there is still only red- ness of the tonsils, the epithelium swells, then its cells are glued together, and the false membrane is formed at the expense of a transformation and deformation of the epithelium different from that described by- Wagner, but ending in the same result, an epithelial reticulum. Thus there is formed a network con- taining in its meshes leucocytes and fibrin in a fila- mentous state. If the duration of the false membrane is ephemeral, and if recovery is rapid, the process is arrested here; there is a complete disintegration of the exudation, which disappears, and a new epithe- lium is formed on the surface of the mucosa. If the disease continues, the epithelial reticulum undergoes disintegration, and to replace it the derm throws out fibrin and leucocytes which coagulate into a fibrino- purulent membrane. Little by little the metamor- phosis goes on until there remain in the false mem- brane only a few granulo-fatty epithelial cells, and it is constituted throughout its extent by a fibrinous net- work containing leucocytes and a few red blood- corpuscles. In the laryngo-bronchial false-membranes, vacu- oles indeed form in the disaggregated epithelial cells, but there develops rapidly a fibrinous exudate which sometimes traverses the dissociated epithelium to constitute on its surface a more or less thickened muco-purulent fibrinous false-membrane; sometimes it raises the epithelium and forms under it a fibrino- purulent layer. — i3° — Leloir shows that there is no difference, macro- scopic or microscopic, between the false membrane of diphtheria and that which is produced by experiment- ally irritating the pharyngeal mucosa, or which de- velops in herpetic angina, on mucous patches, indu- rated chancres, blisters, etc. In fact, the false mem- brane is only a pustule or a mass of confluent pus- tules, of which the centre is bare by reason of the absence of the horny layer. Cornil has also studied the false membrane in diphtheria. He admits that the exudate is formed at first of a stroma of epithelial cells and leucocytes, then becomes entirely fibrinous. There is first a de- generation of the investing epithelium; then this is lifted up and detached by the migratory cells, which, by reason of the inflammation, issue in great abund- ance from the vessels of the mucosa. Later, when this epithelium is destroyed and does not form again,, the false membrane is constituted only of a reticulum of fibrin and of leucocytes. To sum up: It is admitted that the false mem- brane, wherever located, is always essentially the same. The importance of the epithelium in the formation has been much exaggerated; we indeed find pavement epithelium, especially at the outset, in the pharyngeal exudate, but fibrin is the principal element of the false membrane. The Loeffler bacillus in contact with a mucous membrane produces an inflammation, which manifests itself by the transudation of fibrin through the vessels, and by diapedesis of leucocytes. While the false membranes experimentally produced — by means of ammonia, for instance — are not, after removal, repro- duced in the throat, the exudate of diphtheria is renewed as long as the cause that has produced it (the specific bacillus) remains present and preserves its virulence. These successive exudations may give a stratified aspect to the false membrane. The false membrane may disappear in two ways: either it undergoes disaggregation, or it falls off. In the first case the fibrin loses its fibrillary character, be- comes granular, may be transformed into mucin, soft- ens, becomes diffluent, separates in fragments, and disappears. This process is accompanied by a notable diminution or even complete disappearance of the specific bacilli in the exudate, which is invaded by a host of other microbes; these bacteria probably con- tribute thus to alter the constitution of the false mem- brane. The pseudo-membrane may become detached from the mucosa when the inflammation diminishes and the diapedesis and transudation of fibrin cease. The mucosa, on becoming normal, secretes mucus, which, insinuating itself between the surface of the mucosa and the exudate, breaks the filamentous adhe- sions which join the two, and detaches little by little the false membrane, allowing it to fall off. 2. Lesions Produced by the Diphtheritic Poison. — Bretonneau, in endeavoring to demonstrate that the false membrane is not an eschar, affirmed the absolute integrity of the subjacent mucosa in all cases. He went too far; the mucosa is not unaffected. In the most simple cases it is congested but remains smooth; at other times, the inflammation being more intense, the mucosa becomes rough and loses its polish. Below the false membrane and in the zone that surrounds it, the chorion is infiltrated to such an extent as sometimes to give rise to oedema of the glottis; the mucosa is spotted with ecchymoses. Often, then, the region invaded is the seat of ulcer- ations more or less deep. Lastly, in certain malig- nant forms the mucosa takes on a violaceous tint, the diseased points become the seat of a considerable tumefaction, and a more or less extensive eschar forms which leaves after it a grayish ulceration secreting a fetid sanies. Roux and Yersin, in cases of experimental diphtheria (with the Loeffler bacillus alone), have observed destructive lesions of the affected region; these eschars at the point of inocu- lation have been reproduced by the injection of filtered diphtheritic culture-broths. The action of the poison then suffices to deter- mine vascular thromboses, which entail either frag- mentary destruction of the tissues or a more extensive mortification. Then the microbes of putrefaction set up a true gangrene. The histological lesions of the mucosa subjacent to the false membranes have been studied chiefly in the throat and air-passages. In the diphtheritic amygdalites, the false mem- brane is applied to the chorion of the mucosa com- pletely denuded of its epithelium. We find on the points of the tonsils where the false membrane is absent or detached, an epithelium sometimes normal, sometimes constituted of one or two layers of cubical cells irregularly cylindrical or even vesicular, showing a cavity between the protoplasm and the nucleus. The chorion is infiltrated with lymph-cells and red globules. The capillary vessels are filled with white globules; the follicles and reticulated tissue of the tonsils are inflamed, stuffed with lymph-cells. When there is loss of substance of the mucosa, we find along with infiltration of the chorion a softening and sep- aration of the connective-tissue fibres by fatty granu- lations, as well as the presence of little haemorrhagic foci here and there. In cutaneous diphtheria, the horny layer has dis- appeared, and the derm subjacent to the false mem- brane is thickened, red, indurated, and uneven; the subcutaneous cellular tissue is infiltrated and tumefied so that the borders of the ulceration are very salient and violaceous. The rete mucosum and superficial layer of the derm react precisely as the epithelium and chorion of the mucous membranes, as seen by the microscope. All the glands are subject to engorgement, espe- — 134 — daily the submaxillary and parotids. At the autopsy, the bronchial and even the mesenteric glands are found hypertrophied. The engorged glands may fuse together and form a coherent mass, which by its size may cause compression symptoms. The cellular tissue around the affected glands is infiltrated, and the entire region deformed, tense, and hard. Section of these glands presents the red or red- dish-brown color of intense inflammation. The hyper- trophied follicles appear as opaque, white, brilliant granules. Centres of necrobiosis have been described. Morel refers these lesions to the irritation of strepto- cocci in the gland-parenchyma, these microbes being always present. The necrobiosis would, then, be the result of a secondary infection. He thinks that the diphtheria poison causes hypertrophy of the follicles, manifesting itself by a considerable accumulation of leucocytes which stain vividly. The blood-vessels are dilated and contain numerous leucocytes; but the stroma, the sinuses, and the capsule of the gland pre- sent no alteration. In cases where the lesion depends only on the action of the diphtheritic poison, no micro-organism is seen in the sections. The submaxillary and parotid glands present a considerable augmentation of volume, have a yellow- ish hue, and seem to be the seat of an oedematous infiltration. The histological examination shows pro- found lesion of their elements. The connective tissue — i35 — which surrounds the gland and its lobules has pro- liferated. The epithelium of the acini is first simply- swollen and translucid, then it becomes granular and contracts; it may finally so multiply as to obstruct the gland cavities by cells of new formation. In many points the lobular ducts and acini are surrounded by little miliary abscesses. The production of pus in these cases must depend on secondary infections. Generally voluminous, the liver presents the ex- ternal aspect of congestion; it is deep red in patients who have succumbed at the onset of diphtheria. In cases that have lasted longer it is pale, often mottled with yellowish-white patches, indicating fatty accu- mulation. On section, no liquid is seen to ooze ex- cept in the early stage of congestion, when a little dark, thick, sanious fluid escapes. The microscope shows dilated capillaries and fatty infiltration of their endothelial cells and of the hepatic cells. It is a true infiltration and not a degeneration of the hepatic cells, for the latter remain living — their protoplasm is not modified, their nuclei continue to stain well; at the same time, in some cases their volume is notably diminished. The fatty accumulation may be peri- portal; it may be around the hepatic veins or occupy the entire extent of the lobule. Masses of embryonic cells may accumulate in the connective tissue of the portal spaces, forming nodules. The vessels contain a great many leucocytes. In short, the lesions are nearly the same as those met with in the liver in the course of all infectious diseases. — i3 6 — Degenerative lesions of the gastric mucous mem- brane are common in diphtheria affecting the stomach — the epithelium disappearing, subepithelial necrosis may follow. The intestine often shows traces of catarrhal enteritis, with tumefaction of its follicles and glands. The spleen is congested and hypertrophied, the Malpighian corpuscles white and brilliant; the micro- scope shows an enormous accumulation of round cells around these corpuscles. The lesions of the kidney are those of congestion or of parenchymatous nephritis, in general little pro- nounced. These lesions are often not symmetrical. When there is simply congestion, the kidney is aug- mented in volume, of reddish color, its external sur- face strewn with deep-red points (Verheyen's stars). On section, the congestion is found to be limited to the cortical substance, while the medullary substance remains pale. — When there is nephritis, the kidney is yellow, soft, mottled with spots of a clearer yellow; the cortical substance seems augmented in volume, is pale on section, and trenches by its prolongations on the medullary substance, which is very red; the capsule of the kidney is healthy, easily detachable without tearing the parenchyma. Under the micro- scope the principal lesions, when but little advanced, are seen to be dilatation of the blood-vessels and some cloudy swelling of the epithelium of the con- voluted and collecting tubes — these alterations are — i37 — similar to those produced by phosphorus or arsenic, especially the latter; the glomerule is simply con- gested, its vessels distended and full of globules; there is rarely any exudation between the capsule and capillary tufts. In a more advanced stage, the epithelium of Bowman's capsules is in places degen- erated and desquamated, in other places undergo- ing proliferation; there is a serous exudation, with blood-globules and epithelial debris in the cavity of the capsule; in the straight and collecting tubes the epithelium contains numerous fine fat globules; there are little hemorrhagic foci under the capsule, and a granular detritus in the large convoluted tubes. All these alterations seem due to the intoxica- tion, and not to any secondary infection, for all who have sought for microbes in a diphtheritic kidney have failed to find any. The heart is generally increased in size. If in many cases pathologists have noted the flabby con- sistence and dead-leaf color of the organ when spread out on the post-mortem table, it is not rare to observe under the microscope the lesions of acute myocarditis in a diphtheritic patient whose cardiac tissue remains firm, red, and of normal aspect. The heart is dilated, but not hypertrophied. Its weight is little if at all increased. Generally its cavities and large vessels are full of clots, which are either soft, like currant jelly (especially in the right cavities), or half fibrinous, half cruoric, prolonged into the blood-vessels. When - 138 - the heart cavities are emptied of their clots, you will often see under the endocardium ecchymotic spots, and the same may be observed, though rarely, upon the pericardium. There is a general or limited red- ness at the free border of the valves, and mam- millated prominences forming a crown on the upper aspect of the valves, principally of the mitral. The red coloration of the endocardium is a phenomenon of cadaveric imbibition. The mammillated projec- tions are the product of fibrous transformation of little haematomata developed on the valves during early life, and perhaps even during intra-uterine life. The histological lesions affect all the elements of the structure of the cardiac muscle; they are met with in the walls of the left ventricle near the apex, and near the columns of the mitral valve. When you dissociate the muscular fibres, you observe that they are very fra- gile; they are fusiform, tumefied, in many points granu- lar, have large nuclei which stain easily and possess one or more very refractive nucleoli. The muscular fibres may undergo two kinds of degeneration, and present either the granular or granulo-fatty aspect or the vitreous transformation. In the granular degenera- tion the granulations are irregularly disseminated, or disposed side by side in chaplets along the fibre. In the vitreous degeneration the fibres present one, rarely two or three, degenerated patches in their course. The vitreous block is spherical or fusiform, and crowds to one side the striated substance, swell- — i39 — ingthe fibre and forming a node in its course. These two modes of degeneration may be met in the same specimen; the fibre interrupted by waxy blocks pre- sents here and there throughout its whole extent a crop of dark granulations. The connective tissue takes on an abnormal development. The internal perimysium is infiltrated with embryonic cells, in the midst of which appear debris of granular muscular fibres, degenerated, or masses of fatty granulations, the' last vestiges of atrophied muscular fibres, or, per- haps, little haemorrhagic foci which testify to vascular intra-muscular ruptures. In short, the diphtheria poison determines both a parenchymatous and an in- terstitial lesion. It also causes an arterio-sclerosis of the vessels of the heart. The vasa-vasorum situated in the outer coats are the seat of an obliterating endovascularitis. The walls of the arterioles thicken, and their lumen is often filled by a thrombus adher- ent to their walls. The blood presents modifications of color and consistence, which are especially seen in the malignant and asphyxiating forms of diphtheria. It is then blackish or brown, and has a sepia tint; more rarely it has the appearance of currant jelly or simply red- dish water. It is probable that the fibrin of the blood increases as in most general infectious diseases. The researches of Quinquaud, L^corche" and Talamon and Binaut, have shown that in diphtheria there is an augmentation of the white globules, the more marked — 140 — the graver the diphtheria. The number of red glob- ules diminishes, and, according to Quinquaud, the power of absorption of hasmoglobulin for oxygen diminishes as the disease becomes more grave. There is also a great augmentation of the extractive matters of the blood, while the salts of potassa are notably diminished. The symptoms which seem to depend on the alteration of the nervous system are not always ex- plained by the lesions found at the autopsy, Very complete and extensive paralyses have been noted in subjects whose nervous systems presented insignifi- cant alterations or none at all. We may, then, affirm, in reference to such cases, that the diphtheria poison may profoundly modify the function before altering the organ. The lesions of the peripheral nerves and nerve-roots have been noted in many isolated cases since Charcot and Vulpian, in 1862, noticed in a case of diphtheritic paralysis of the velum pendulum a lesion of the palatine nerves characterized by the reduction to granulo-fatty droplets of a certain num- ber of nerve-tubes, a lesion similar to what is observed at the peripheral end of a divided nerve. Dejerine has studied several cases of diphtheritic paralysis, and has always noticed in the anterior spinal roots a lesion which corresponded exactly by its seat with the para- lytic phenomena observed during life, and which was the more marked the longer the paralysis had lasted. This lesion was identical with the Wallerian degener- — i4i — ation, characterized by the moniliform aspect of the nerve-tubes, in which the myeline breaks up into fat drops by the complete disappearance of the axis- cylinder and a multiplication of the nuclei of the sheath of Schwann. The posterior roots were normal. The examination of the peripheral nerve was made in only one of these cases. Dejerine noticed these empty nerve-sheaths, in the midst of other tubes that were perfectly normal. He describes, at the same time, slightly marked lesions of the spinal cord, limited to the gray substance, but more particularly to the ante- rior cornua (nerve-cells less numerous, less refractive; multiplication of the elements of the neuroglia; con- gestion of the vessels). Gombault, whose researches have been con- firmed by the observations of Gaucher and Meyer, has established the nature of the lesions of the roots and peripheral nerves in diphtheritic paralysis. It is a periaxile segmentary neuritis, of which the Wallerian degeneration is the possible if not necessary termina- tion. There is first a segmentary alteration affecting only a limited extent of the length of the fibre, located in one or more annular segments, often in a part of the segment only. When you follow the same fibre along its entire course you will not fail to meet the same lesion several times, each diseased seg- ment being separated from those nearest by intervals of fibre absolutely healthy. The diseased fibres have a tendency to group themselves into bundles; at the — 142 — same time, diseased fibres may be met with in the midst of healthy fibres. The segmentary lesions begin at one of the extremities of the segment; they then gain the other, and finally the middle portion. The lesion takes on two different aspects: there is a phase of degeneration, and a stage of regeneration. These two aspects are frequently associated in the same interannular segment. In the stage of degen- eration the myeline becomes granular; in certain points of the nerve tubes there are large protoplasmic masses containing numerous nuclei; elsewhere the axis-cylinder, under the form of a simple tractus, is covered at the level of the granular swellings with myeline, but remains always continuous. When the fibre is regenerated it is thinner at the point where it has been diseased— and the segments that have been affected are shorter than normally— but its sheath of myeline is perfectly homogeneous and is depressed at the level of the nuclei; its contours are sharply arrested. The degeneration of the fibre does not always retrocede, and the axis-cylinder may be- come interrupted by a sort of spontaneous destruction similar to what we see in acute myelitis. You will note then, in a segment of neuritis, moniliform swell- ings of the axis-cylinder, which finally fill the primitive sheath; in following the nerve you arrive at a solution of continuity beyond which you no longer find it except under the form of isolated trunks between the blocks of myeline. From this point, where there is — 143 — rupture of the axis-cylinder, the entire peripheral end of the nerve fibre undergoes a Wallerian degenera- tion. Thus you will note these lesions alongside of those of segmentary peri-axile neuritis, of which they are the consequences. Pitres and Vaillard, in exam- ining the nerves in a case of diphtheritic paralysis, have found the lesions described by Gombault. But in the fibres affected with segmentary neuritis they have not been able to stain the axis-cylinders. Lastly, Babinsky has not succeeded in finding the histological lesions of the nerves in experimental diphtheritic paralysis. The spinal cord has generally presented an aspect nearly normal; in some cases the large motor cells of the anterior cornua were filled with dark, voluminous granulations which completely concealed their nuclei and resembled those met with in the course of myelitis. The meninges present exceptionally the appear- ances of inflammation with fibrinous exudation. This meningitis may invade the gray substance of the cord and constitute a meningo-myelitis, involve the whole extent of the bulbo-spinal meninges, or localize itself in the bulb and cervical cord. In the cerebrum, lesions have been very rarely found; those which have been noted were sanguineous extravasations with peripheral softening, simple cere- bral congestion, turgesence of the sinuses, serous suf- fusion of the meninges, oedema of the ventricles, etc. — 144 — Inflammation of the meninges is quite exceptional and is always due to secondary infections. The muscles may be altered in diphtheria; writers have noted granular degeneration of their fibres. The fibrillary elements of the primitive fasciculi lose their cohesion and easily separate; their transverse striation is effaced; the fibres contain proteinaceous or fatty granulations, but there is no alteration of neuclei or sarcolemma. Labadie-Lagrave has re- ported a case in which the muscles presented the waxy transformation. These alterations have been especially studied in the muscles subjacent to the in- flamed mucous membranes, larynx, and soft palate. They are pale, of a dead-leaf color, cedematous, and friable. In the larynx the extrinsic muscles are rarely degenerated; it is the thyro-arytenoidei which are most generally affected. 3. Lesions Due to Secondary Affections. — Ulceration and gangrene of the mucous membranes are exceptional in diphtheria. We have seen, however, that the diphtheritic poison may of itself in certain cases determine losses of substance in mucosae covered with false membrane. The streptococcus pyogenes, so often associated with the Loeffler bacillus, may also pene- trate the mucous membranes and determine profound ulcerations: the case is similar to that observed in the pseudo-diphtheritic anginas of scarlatina where we find extensive losses of substance underneath the false membrane, and can easily stain by Gram's method — 145 — the micrococci in chains which profoundly penetrate the diseased mucosa. When the subject is very much debilitated, and the microbes of putrefaction obtain a habitat in these ulcerations, the base becomes toment- ous and grayish, the borders are excavated, and there is gangrene at the level of the losses of substance. This is met with on the tonsils and soft palate, where it may cause perforation. The gangrene may pene- trate the cellular tissue below the mucosa and extend to the large vessels of the neck. Necrosis of the larynx and its cartilages is rare. The gangrene may be complicated with cutaneous diphtheria and invade the tracheotomy wound after this operation. The histological lesions of the glands have been well studied by CErtel and Morel. These alterations pertain especially to the follicles, which stain poorly by picro-carmine. Little alveolar abscesses form in the necrosed connective-tissue stroma. In points where the lesion is less advanced, we see in the region of the follicles a finely granular amorphous tissue in which may still be seen a few round-cell elements, which stain indifferently by carmine and present the characters of coagulation necrosis. Masses of strep- tococci are found in the little alveolar abscesses and degenerated follicles. The inflammations of the endocardium or men- inges are complications quite exceptional in diph- theria. The cutaneous modifications corresponding to — 146 — erythemata have been studied by Lewin and Leloir. They present nothing that is special to diphtheritic erythemata. We know that each arteriole of the skin irrigates a little circular territory, the arteriole dividing and spreading itself out into ramifications in the form of a cone, of which the base is tegumentary. If an arteriole is paralyzed, all the corresponding territory is congested and forms a red spot. At the onset of an erythema, the congestion usually shows itself in an unequal degree in these different vascular territories, so that paler areas are observed between the red spots before the erythema becomes general. When the blood-pressure equalizes itself over all the vascular territories, the coloration of the skin becomes the same everywhere and we have the scarlatinoid erythema; and if there is exudation under the epider- mis, there will be found vesicles or bullae. When the congestion remains limited to little islets, but is still active and there is oedema and diapedesis from the hyperaemic zones, the eruption takes on the papulo- tuberculous aspect. If the blood-pressure becomes too strong in the territories invaded by the erythema, the red blood-corpuscles issue from the vessels, and we have the purpuric erythema. The most frequent pulmonary lesion of diphtheria is broncho-pneumonia. It is the consequence of a secondary infection, due to the streptococcus pyogenes. This micro-organism is the agent of most of the broncho-pneumonias, whether primary or secondary. — 147 — In six cases out of seven the broncho-pneumonia of diphtheria takes on the form of disseminated nodules; the pseudo-lobar form which is met with in one out of seven cases occupies chiefly the posterior bronchial system, generally towards the inferior border. Atelectasis is constant and always very ex- tensive. It may be the only pulmonary lesion. In no disease but whooping-cough is the vesicular emphysema more marked; rarely it becomes inter- lobular and subpleural. The abundance of the fibrin- ous exudate in the alveoli is a character of the broncho-pneumonia of the diphtheritic. In certain cases the fibrin, under the form of ramified and an- astomosing tracts, almost fills of itself a whole group of alveoli. This network contains a few leucocytes, red globules, and epithelial cells. Its. aspect might lead one to believe that he had before him a frank pneumonia at the period of hepatization, if these points were not immediately surrounded by zones showing wide disparities in the state of development of the characteristic lesion. These abundant de- posits of fibrin are met with in cases where the false membranes have extended to the small bronchi, but they are also found in cases where the membranes are arrested at the larynx or trachea; there is, then, no necessary relation between the two processes. Another elementary lesion whose frequency is rather peculiar to diphtheria, is constituted by hemor- rhagic foci in the midst of the pulmonary parenchyma. — 148 — Balzer has made a study of them, and assigns as their habitual seat the posterior and inferior part of the lungs. , The blood effused circumscribes the peri- bronchial nodules, and deforms but never entirely penetrates them. It is probable that we have to do here with haemorrhages due to the peri-nodular con- gestion and penetrating the lobules primarily affected with the pneumonia. Microscopic preparations made from sections of the bronchial nodules show the streptococcus, and sometimes the pneumococcus and Lceffler bacillus. I cannot close this chapter without saying a few words concerning the lesions produced in the organ- ism of animals by experimental diphtheria. The researches of Babes have shown that the lesions obtained by inoculating the Loeffler bacillus in animals are very like those met with in the organs of children that have died of diphtheria. The simi- larity becomes much less evident when the inocula- tion is performed with diphtheritic cultures that have been filtered through porcelain. New researches will be necessary to explain these differences. TREATMENT. It is not my intention to review here the innu- merable kinds of treatment which have been proposed for diphtheria. Their very multiplicity sufficiently indicates the little efficacy they possess. I shall only attempt to set forth what appear to be the most ra- tional precautions and therapeutic measures for the physician to adopt when he finds himself in the pres- ence of a case of diphtheria. I shall start from the postulate, absolutely demonstrated to-day, that the germ of diphtheria is exclusively contained in the false membranes and products of expectoration, which when dried keep the germ active a long time and may thus easily transmit it in a state of virulency. When the physician is called to a patient affected with diphtheria, what should he do ? Even when there is some doubt as to the diph- theritic nature of the affection, the same precautions should be taken as if the diagnosis were certain. The carriage which the patient occupies in transit to the hospital must be disinfected immediately after. In Paris we have special carriages placed at the dis- posal of physicians for such purposes. If the patient is not to be removed anywhere, he must as far as pos- sible be isolated, no one but his regular attendants being allowed access to him. If children live in the house, they should not only be excluded from the room, but if possible sent away during the time — iffo — of sickness and till after thorough disinfection of the house has been effected. These same children should also be kept under observation and away from other children during the first fortnight. Nurses and at- tendants on the patients should rigorously observe the following rules: Take no drink or nourishment in the sick-room; keep the hands clean with a brush and soap-suds, and occasionally rinse them in an anti- septic solution; bathe after every contact with an infected object; renew these ablutions always on leaving the sick-room and before eating. It would be a good plan for every attendant to wear a special suit while in the patient's room; this can be laid aside when he leaves the room. All cracks or abrasions about the hands or face must be instantly painted with collodion. The nurse should avoid taking the patient's breath, especially during fits of coughing. Nor should the nurse neglect to take a walk in the open air once or twice a day, or overlook the neces- sity of sleeping in a room apart from the patient. Similar precautions are equally necessary for the attending physician. There are two sorts of antiseptic solutions to be used: one strong, the other weak. The former con- sists of corrosive sublimate, one part to a thousand; this should be stained with fuchsin, and acidified with ten parts of hydrochloric acid: Corrosive sublimate, i part. Hydrochloric acid, 10 parts. Water, iooo parts.',' Useful-antiseptic solutions are also the following: cup. sulph., 5-per-cent.; calcium chloride, 5-per-cent; milk of lime, 20-per-cent.; zinc chloride, i-per-cent. To obtain a very active milk of lime, take a certain quantity of quick-lime of good quality, and slack it by wetting it slowly with half its weight of water; when the slacking is completed, put the powder in a bottle, cork tightly and set away in a dry place. As a kilogramme which has absorbed 500 grammes of water in order to undergo slacking has acquired a volume of 2 liters 200 cubic centimeters, it suffices to suspend it in double its volume of water {i.e., 4 liters, 400 Cc.) in order to have a milk of lime which shall be about 20 per 100. The feeble solutions which are most efficacious are the following: corrosive sublimate, 1 per 2000; phenic acid, 5 per 1000; sulphate of copper, 2 per 100; chloride of lime, 2 per 100; milk of lime, 7 per 100. The first two of these feeble solutions are best for the ablutions of the patient or his attendants. As soon as a case of diphtheria is recognized, all •curtains, carpets, wearing apparel, and every article of furniture which is not indispensable should be re- moved from the sick-chamber, and immediately dis- infected, either in the dry stove under steam pressure, or by washings with a suitable solution from among those above mentioned, or by sulphur fumigations. The bed should be located in the middle of the room. Aeration of the room must be effected several times a — i5 2 — day; sawdust wet with one of the strong disinfectant solutions should be sprinkled over the floor every day, the room then swept, and the sweepings immediately burned. The body-linen, towels, bed-clothing, dress- ings, etc., ought to be immersed for two hours in one of the strong solutions, and then kept in boiling water for half an hour, before the final washing. All objects that have been in contact with the patient may trans- mit the disease; care must therefore be taken that all surgical instruments, as well as domestic utensils, knives, forks, spoons, cups, etc., after being used, be placed in boiling water, and kept there for five minutes at least. It will be well to destroy all books and playthings which have been handled by the patient. The matters vomited or expectorated by the patient, the stools, and the urine, should be immedi- ately disinfected with one of the strong solutions. A cupful of the solution having been poured into the vessel, the vomitus, expectoration or dejecta should, immediately after passage, be buried or poured into water-closets which are disinfected twice a day with a strong solution of milk of lime. The better way would be to bury them in a deep hole in the ground, first covering with the strong chloride of zinc or other disinfectant solution. A place should be chosen which is at a distance from any water-source. The dejecta must not be thrown onto manure heaps or into water-courses. It is important in the presence of a case of — i53 — diphtheria that the physician should make a careful inquiry to determine its origin; he will thus often be able to circumscribe and arrest an epidemic. More- over, every case of diphtheria should be at once reported to the board of health. All these precautions should be indicated by the physician at the date of his first visit. Local Treatment. — The prevalent conception of diphtheria, which makes of it a disease quite local at the outset, the patient subsequently being consti- tutionally poisoned by the products elaborated at the point of infection, gives a capital importance to the local treatment of the disease. Cauterization of the parts invaded by the false membrane is not a new method, and we know the use which Bretonneau and Trousseau made of hydrochloric acid for this end. But the recent conquests of bacteriology have given more assurance to the physician, and he has thereby learned the crucial point to which his efforts should be directed. M. Gaucher was the first to popularize a rational treatment of diphtheria. This method is to-day everywhere employed in this country, though with some modifications. His mode of treatment in- cludes three stages: (i) Ablation of the false mem- branes; (2) Painting of the diseased parts with a strong antiseptic mixture; (3) Irrigations of the bucco-pharyngeal cavity with a weak antiseptic solu- tion. These three stages of treatment should be — i54 — regularly repeated every three or four hours, even during the night, and oftener still if the false mem- branes are rapidly reproduced. The ablation of the false membrane is made by means of a soft-wool brush invented by Dr. Cr^san- tignes. The mouth must be opened with a tongue- depressor, and kept open if necessary by means of a wedge, and the false membrane removed very gently, care being taken not to corrode the mucosa and make it bleed. As far as possible the throat should be cleared of all the false membranes which cover it, then painted by means of a suitable swab with the following mixture: Camphor, 20 Gm. Castor oil, 15 Gm. Alcohol, 10 Gm. Crystallized phenic acid, 5 Gm. Tartaric acid, 1 Gm. This mixture is sufficiently caustic to require care on the part of the physician not to touch with it the tongue or the sound parts of the mucous membrane of the mouth. As fast as the false membranes are detached, and while there remain any floating shreds in the throat, it is well to make from time to time large irrigations of the bucco-pharyngeal cavity and nasal fossae with a feeble antiseptic solution (phenic acid, 1 per 200), These irrigations are made by means of an ordinary fountain-syringe with straight cannula, care being — i55 — taken to have the headf of the child bent over a pail or other vessel to prevent swallowing the solution. After each cauterization with the mixture, a period of ten minutes is allowed to elapse, to give the topical remedy time to act, then a copious irrigation is made with a weak solution; in very young children it is better to employ boiled water. Instead of the Gaucher mixture, the sulphoricin- ated phenol may be employed with equally good re- sults; the bichloride or biniodide of mercury, i part to 200 or 300; or the camphorated phenol. Crystallized phenic acid, 5 Gm. Camphor, 20 Gm. Alcohol, 10 Gm. Gycerin, 25 Gm. The camphorated naphthol is a good preparation: Naphthol, 10 Gm. Camphor, 20 Gm. Glycerin, 30 Gm. Salicylic acid may also be used in weak solution, 1 or 2 per 100. Perchloride of iron, pure, or mixed with equal parts of glycerin, is also in use; also tincture of iodine; lastly, permanganate of potash, 1:10, with which I have obtained in a series of clinical trials results very similar to those which others claim to have derived from Gaucher's mixture. M. D'Espine prescribes lemon-juice, which is a very old remedy in diphtheria. Good authorities employ also for irrigations - 156 - boric-acid solutions, 3 or 4 per 100; lime-water; chloral-water, 1 per 200; salicylic acid, t per 1000; and peroxide of hydrogen. Some conjoin with the above, antiseptic sprays. With a suitable hand-ball spray-producer, spray the mouth and throat of the patient with the antiseptic solution. Or steam pulverizations with a boric solu- tion may be made, a Codman & Shurtleff atomizer being employed; the steam is directed as far as possi- ble into the mouth of the patient. The atmosphere of the room may also be saturated with antiseptic vapor by keeping constantly evaporating a weak carbolic solution contained in a great open dish. Sevestre advises to place every ten minutes a little piece of ice in the mouth of the patient. The method of Gaucher, which gives in general very satisfactory results, is not applicable to all cases. The degree of adhesion of the false membrane is very variable. There are diphtherias where the exudate seems to be identical with the mucous membrane, and where all attempt at ablation ends in tearing the mucosa and making it bleed. Often the pseudo- membrane which is easily removable at the onset of the disease, becomes subsequently extraordinarily ad- herent to the underlying mucosa. Sometimes we en- counter infants so refractory that at each swabbing we run the risk of making a traumatism more or less deep in the mouth or in the throat with the tongue- depressor or with the swab forceps, especially when — i57 — the attendant does not well succeed in keeping the child still. It seems to me that these are real contra- indications against swabbing. Such is, moreover, the opinion of M. Roux, who said recently: " I am not at all an advocate of forcible swabbing and ablation of the pharyngeal false-membranes. By these meth- ods one cannot help continually wounding the sur- face of the tonsils. In destroying the false mem- branes you destroy also certain parts of the mucosa, and you create new points of absorption for the toxine which is being continually produced by the microbes which pullulate in the epithelium. It will not do to believe, in fact, that even when you have removed all the white patches in the throat you have removed all the cause of the evil; it is far otherwise. There remains always a residuum of bacilli that the most energetic brushings cannot remove. In my judgment it is better practice to content ourselves with antiseptic irrigations, abundant and repeated, made with care and gentleness." The practitioner will, then, limit himself to irrigations of the throat with one of the solutions which I have indicated above, whenever he has reason to fear that, by attempting to swab, he will wound the mucosa. The local treatment which I have described is chiefly applicable to diphtheritic angina; but it is also employed, whatever may be the seat of the false membranes, whenever they are directly accessible. When the diphtheria is developed on a cutanepus - i58- surface, it is necessary besides to cover the wound with an occlusive dressing which will prevent the dis- semination of the disease. Whenever the false membrane invades the larynx it constitutes a mechanical obstacle to respiration which may necessitate tracheotomy. I shall not here describe this operation or its sequelae; but it is well to remember that, except in certain cases where the very intense and oft-repeated paroxysms of suffocation threaten sudden death, it is the rule not to operate until the period of asphyxia, when to the extinction of the voice and the cough is added a dyspnoea not only paroxysmal but permanent, with wheezing and signs of blood-stasis in the capillaries. It is better, in short, to operate at the latest possible moment, and not to forget that often an emetic suitably adminis- tered has enabled the physician to avoid an operation which before seemed necessary. General Treatment. — At the same time that we combat the infection we must arm the organism against the intoxication by subjecting it to an appro- priate general treatment, of which alimentation and tonics form the basis. It is needful, above all, to nourish the patient as fully as possible. It is also necessary to overcome the dysphagia, and the repugnance which the patients rapidly manifest toward food; to have recourse to semi-solid and very substantial articles of diet in — i59 — small volume, such as eggs, meat-juice mixed with thick gruel, creams, scraped or very finely hashed meat. The physician will employ, in case of neces- sity, gavage (forced feeding) and even nutritive enemata. Alcoholic stimulants give also good results, on condition that they are diluted with water and given in small quantities at a time. According to the taste of the patient, he may be allowed to take freely sherry, Malaga, champagne or Bordeaux wine, whiskey punch, tea and coffee. All these liquids are better tolerated and more easily swallowed when they are cold, and even ice-cold. I am in the habit of giving cinchona, under the form of the soft extract, in the dose of two to four grammes per day, in infusion of coffee: 3 Inf. coffee, 125 Gm. Syr. acaciae, 40 Gm. Soft ext. cinchona, 2 to 4 Gm. M. S.: Tablespoonful every two hours. Some think highly of hydrochloric lemonade, 4 per 1000— taken continually by spoonfuls during the day; perchloride of iron, in the dose of one to two drops (liq. ferri chloridi) every two hours; euca- lyptol, dissolved in liquid vaselin, in subcutaneous injection ; two to five grammes of benzoate of soda per day in a potion; hypodermic injections of caffeine or of ether; lastly, inhalations of oxygen. — 160 — Treatment of Certain Signs of Intoxica- tion. — When the glandular engorgement takes on considerable proportions, the practitioner may make inunctions of mercurial ointment over the swollen parts, or he may keep on cold applications, and even apply an ice-bag. In general, the albuminuria is too transitory to indicate a lasting lesion of the kidney. If, however, it is persistent and remains abundant, it will be desir- able to put the patient on a milk diet, while continu- ing to stimulate him with a little brandy. In cases where the gastro-intestinal symptoms assume a certain importance, it may be well to prac- tice intestinal antisepsis by betol or benzo-naphthol. Haemorrhages are rarely so abundant as to re- quire treatment; they imply a profound alteration of the economy which calls for tonics and stimulants. When the heart is gravely affected by the diph- theritic poison, and even when it begins simply to be enfeebled, it will not do to hesitate to resort to the cardiac tonics. Caffeine gives the best results, ad- ministered in potion or in hypodermic injection. In the adult one to two grammes of caffeine may be given per day; in the infant, 25 to 50 centigrammes. Black coffee may be taken at the same time. When myocarditis is made manifest by incontestable signs, give ergotin in the dose of two to four grammes in twenty-four hours. Cutaneous revulsion over the precordial region seems to present more disadvan- — 161 — tages than benefits. Diuretics and the milk diet are indicated in order to cause the elimination of as much as possible of the poison by the renal emunc- tory. For the diphtheritic paralysis the physician can do little but feed the patient and electricize the en- feebled muscles. Alimentation should be very care- fully watched. It is necessary to diminish as much as possible the quantity of liquid aliments when the soft palate is affected by the paralysis. Fluids are then rejected by the nares, or flow into the respir- atory passages, provoking violent paroxysms of coughing, which fatigue the patient and cause repug- nance toward food. Likewise solid food constitutes a danger always threatening; fragments insufficiently masticated may fall into the trachea and determine an access of fatal suffocation. It is better to give panada, thick soups, stews, pap. It may become necessary to employ the oesophageal sound to intro- duce aliments. At the same time, it is necessary to have recourse every day to faradization of the para- lyzed muscles. Some have counseled the galvanic current, for which success has been claimed; the negative pole is placed on the back of the neck, the positive pole over the paralyzed parts. When the paralysis begins to amend, we may attempt to excite the muscular contractility by giving preparations of nux vomica. It must be remembered, however, that at the onset of the paralysis this is in- — 162 jurious rather than useful. The various tonics, hydro- therapy, sulphur baths and sea baths are still precious adjuvants. Treatment of the Secondary Infections. — When below the false membranes there appear patches of sphacelus of considerable extent, it will not do to neglect repeated antiseptic irrigations, and particularly the employment of dioxide of hydrogen; the attempt must especially be made to modify the soil by build- ing up the organism through super-alimentation and tonics. The suppurative adenites should be incised early, especially if the pus has invaded the cellular tissue adjoining the inflamed glands. The least delay at this time may permit burrowing of the pus into the deep regions of the neck, or even to the mediastinum. It must also be remembered that often these abscesses comprise two pockets, united by a narrow tract; the abscesses should be opened by a free incision, includ- ing both cavities. It is necessary to cover with occlusive and anti- septic dressings all suppurative lesions of the skin or cellular tissue (impetigo, whitlows, etc.) which are sus- ceptible of being infected by the diphtheritic bacillus. Treatment may be efficacious in the tardy bron- cho-pneumonias; it is rarely so in the early forms.. At the onset, emetics have been recommended; these, however, should not be continued, on account of the - i6 3 - gastric troubles which they entail. The physician should have recourse to generous diet (milk, broth, in small quantities), tonics, and alcohol. Legroux employs systematically as internal treatment, glycerinized creosote in rum, to combat and even to prevent the broncho-pneumonia. Potions may be given contain- ing an expectorant (kermes, or the white oxide of an- timony) or tincture of digitalis. Dry cups constitute an excellent means of revulsion, preferable to the fly-blister. The latter should be absolutely proscribed in young children, mustard sinapisms being used instead. Following tracheotomy, certain prophylactic measures against broncho-pneumonia are absolutely indispensable: a muslin band passed across the orifice of the cannula, a constant temperature from i6° to i8° C. (57 to 6i° F.), and saturation of the atmosphere of the room with the vapor of carbolic acid from a plate containing this liquid in a state of evaporation. Hygiene of Convalescence. — We know that frequently, when the false membrane has disap- peared, the diphtheria bacillus still maintains a habitat in the mouth of the patient, and with all its virulence. It is necessary, then, long to continue the antiseptic lavages of the buccal cavity. It is also well to keep the convalescent away from other children for a month or more. Before allowing him to associate with other children again, it will be pru- — 164 — dent to make him take one or more sublimate baths, or, if that be not possible, a bath of soap and water, followed by lotions of corrosive sublimate 1: 1000. At the end of convalescence, to complete the toning up of the constitution, the patient may be sent away for change of air, to the country or sea-side. All the objects which have served for the daily use of the patients must be disinfected at this time if they have not been before. This disinfection is effected by prolonged boiling, or by exposure to steam under pressure. The room that the patient has occupied must not be again used until after complete disinfection by one of the following processes: 1. Disinfection by Corrosive Sublimate. Disinfec- tion of the bare walls and ceilings should be made methodically by means of sprayings with the strong solutions of corrosive sublimate. The sprayings should be begun at the upper part of the walls, being made along a horizontal line and successively carried downwards, so that the entire surface of the walls shall be covered with a fine stratum of the pulverized liquid. The ceiling should be sprayed in the same manner. The floors, wainscoting and mantels should be washed with boiling water and wiped, then flooded with the sublimate solution; and the room should not be occupied again until after being thoroughly venti- lated for at least twenty-four hours. In case the sick-room has been covered with wall- - i6 5 - papers it will be well to have these scraped off before the disinfection, even at the expense of repapering the room. 2. Disinfection by Sulphurous Acid. Paste a few strips of paper over all cracks which may allow the sulphurous vapors to escape. Remove wall papers and scrape the walls. Burn sulphur, thirty to forty grammes per cubic meter, in the room. To pre- vent the danger of fire, place the vessels containing the sulphur in the centre of iron basins containing a little water. In order to ignite the sulphur, wet it with a little alcohol. Before fumigating the room, it is well to saturate the atmosphere with the vapor of boiling water, for it has been demonstrated that the antiseptic action of sulphurous acid is increased when it is mixed with the vapor of water. When the sul- phur is ignited, close the doors and windows. The room must be kept closed for twenty-four hours; then the doors and windows are opened wide, and left open for forty-eight hours that the sunlight and air may have free access. When a region is the seat of an epidemic of diphtheria, it is well, whenever this is possible, to re- move far from the centre of contagion all persons susceptible of contracting the disease, particularly children. Careful supervision should be made of the drinking-water, which should be of perfect purity, and it is better always to use boiled water for cooking and for drinking. — 166 — The washing of contaminated clothing in water- courses should be prohibited, and such streams should be especially kept free from the dejecta of patients. Milk may serve as a vehicle for the diphtheritic contagion, and should always in times of danger be boiled before being used. We have seen that there exist in domestic ani- mals certain pseudo-membranous affections which do not appear to have the same origin as human diph- theria. When these diseases have been observed in a stable or barnyard it will be well to isolate the affected animals, more for the safety of the animals remaining healthy than to arrest an outbreak of human diph- theria. There are certain general measures of public hygiene which should be attended to. All the causes which prepare the soil for the invasion of epidemics should be removed when diphtheria prevails. It is necessary to have a close supervision over groups of children such as are assembled in schools, and in times of epidemic make frequent examinations of the throat; and school children should be required twice a day to gargle the mouth with an antiseptic solution. Should several cases of diphtheria occur at short intervals in a school, there should be no hesitation in closing the school. Besides, the rules of general hygiene applicable at all times should be still more rigorously observed, especially in what concerns the purity of the drinking-water; aggregations of indi- - i6 7 - viduals, as on holidays and at fairs; the superintend- ence and provisioning of the markets; the cleanliness of the soil; the careful control of water-sources, and the investigation of possible causes of infection; the regular removal of all night-soil; the cleanliness of dwelling-houses; the careful inspection of work-shops, dock-yards, etc., destined for the laboring and indus- trial population; the purification and regular disin- fection of water-closets, public and- private; and the maintenance of a perfectly intact and well flushed sewerage system. INDEX. A. Page Ablation of false membranes * 154 Albuminuria in diphtheria 75 Alcoholic stimulants in diphtheria xxi, 159 Animal diphtheria 58 Antisepsis in diphtheria viii, 150-156 Antiseptic solutions for diphtheria 150 Aviary diphtheria 60 B. Bacillus of Loeffler 23 Bacteriology of diphtheria 12 Billington xii Blood, the, in diphtheria 139 Boric-acid solutions , 156 Bovine diphtheria 61 Bretonneau , 3, 5, 132 Broncho-pneumonia in diphtheria 92, 114, 146 — treatment of 163 C. Cadet de Gassicourt xv Caffeine in diphtheritic myocarditis 160 Camphor, phenicated viii, 154 Carbolic acid (see Phenic). Castor oil and camphor mixture 1 54 Cauterizations in diphtheria viii, 154 Cinchona in diphtheria 159 Contagiousness of diphtheria 14 Cornil on false membrane 130 Page Corrosive-sublimate treatment • xiv Cousot xv Croup 63 in the adult 104 Culture of Loeffler's bacillus 21 D. Diarrhoea in diphtheria 76 Diet in diphtheria 158 Diphtheria, clinical forms of 95 definition 1 diagnosis 115 etiology and bacteriology 11 history 3 in adults 104 in animals 58 its poison 38 pathological anatomy 126 prognosis 112 progress, duration, etc 108 secondary infections in 49 symptoms 64 treatment of 150 Disinfection in diphtheria 164 E. Emetics in croup 162 Enemata. nutritious, in diphtheria 159 Ergotin in diphtheria 160 F. False diphtherias 56, 120 Feeding in diphtheria 15S G. C-aucher 153 — 171 — Pag* General treatment 158 Gentian violet 18 Glandular engorgement, treatment of 160 Guelpa xiv H. Heart in diphtheria 78, 137 Home 4 Hydrogen peroxide in diphtheria I5§ Hygiene of convalescence 163 of nurses * 150 of the sick-room 152 Hypertoxic diphtheria no Iron, perchloride of xiv, xx, 155 Irrigations in diphtheria xiv, 156 J- Jacobi xii K. Kidneys in diphtheria 136 Klebs 3, 8 L. Laryngismus stridulus 118 Leloir's views of false membranes 129 Lemonade, hydrochloric 159 Lemon-juice in diphtheria 155 Local treatment of diphtheria (see also Preface) 153 Loeffler 3, 3 Loeffler's blue 17 serum 20 M. Milk as a vehicle of contagion 166 — 172 — Page Milk-of-lime solution 151 Muscles, alteration of, in diphtheria 144 Myocarditis, diphtheritic 80 N. Nerves, lesions of, in diphtheria 140-144 Neuritis 141 O. Oertel xii P. Paralysis, diphtheritic 80 Phenic acid xii, 154 antiseptic mixture 33 Peripheral neuritis 141 Pilocarpine xxi Prophylaxis 166 Pseudo-membranes, histology of 130 Puerperal diphtheria 123 Pulse in diphtheria 78 Q. Quinine xxi R. Resorcin in diphtheria xii Roux and Yersin 3, 9, 36, 53, 124 on forcible swabbing 157 Roux's blue 18 S. Secondary diphtherias 106 Smith, J. Lewis xxi Sprays, antiseptic, in diphtheria 156 Steam pulverizations 156 — 173 ~ Page Sulphoricinated phenol 33, 155 Syphilides, pseudo-membranous 125 T. Thrush differentiated from diphtheria 117 Tracheotomy 93 Trousseau 4, 5 U. Urine in diphtheria 75 V. Virchow on false membranes 128 W. Wagner's description of false membranes 12S Weak antiseptic solutions 151 Y. Yersin (See Roux). Z. Zannelis. xxii BROMELIN. A digestive principle from Ananas sativa, Schult. (common Pineapple). The discovery by Senor Vincente Marcano, of Caracas, Venezuela, that plants of the natural order Bromeliaceae contain a proteid-digesting principle simi- lar in its effects to pepsin, has excited a great deal of interest. The common pineapple is the best known repre- sentative of the family in question, and the discovery therefore constitutes a scientific endorsement of the empirical reports that are continually emanating from the Southern States of the efficacy of the juice of this fruit in the treatment of diphtheria and so-called diph- | theritic sore-throat. Papain, another well known vegetable ferment, has been used in these troubles for a considerable time, but, owing to an inherent deficiency, its digestive strength is so slight that little success attends its use. This preparation of Bromelin, on the other hand, is found to possess extraordinary powers in dissolving and removing the false membrane of diphtheria and other morbid exudates. We therefore invite for it a careful trial, confident that the results will justify all that has been said in praise of pineapple-juice. PARKE, DAYIS & CO., DETROIT, NEW YORK, KANSAS CITY, U. S. A. LONDON, ENG., «nd WALKERVILLE, ONT. BUE)E)ETIN «»* PUBLICATION^ -OF - GEORGE S. DAVIS, Publislier. THE THERAPEUTIC GAZETTE. A Monthly Journal of Physiological and. Clinical Therapeutics. EDITED BY H. A. HARE, M. D., G. E. DeSCHWEINITZ, M. D., EDWARD MARTIN, M. D. SUBSCRIPTION PRICE, $2.00 PER YEAR. THE INDEX MEDICUS. A Monthly Classified Record of the Current Medical Literature of the World. 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