AND ITS LENNOX BROWNE CORNELL t'- UNIVERSITY. /- '"' ' THE BosracII p. 3'loiMcr ?Librarg THE GIFT OF ROSWELL . P FLOWER FOR THE USE OF | THE IN. Y. STATE VETERINARY COLLEQE. I8.J7 RC 138.6.888"""'"^""'^'"^^^ ,. °',P^'fieria and its associates 3 1924' OOO' 290 183" r^ Cornell University Library The original of tiiis book is in tine Cornell University Library. There are no known copyright restrictions in the United States on the use of the text. http://www.archive.org/details/cu31924000290183 Every increase of knowledge brings before us a larger and clearer view of the immeasurable quantity which is still to be gained. The more we know, the more can we see, if we will, how much more there is that we do not know. Where are we to stop 1 I do not know more than this : that we must not stop where we are ; we must go on and on, and we may be sure that they who work to find the truth will not work in vain. Sir James Paget, Presidential Address to the Pathological Society of London, 1887. DIl^HTHERI/V. Faucial a-spCL-t. ,J^*i^r<; 1'op.t nasal riHpi"-*.:!:. Larj-ngoacopic appearance. /y —^ l*ost rnorte Post mortem ajtpearance. DIPHTHERIA AND ITS ASSOCIATES. LENNOX BROWNE, F.R.C.S.Ed., SENIOR SURGEON TO THE CENTRAL LONDON THROAT, NOSE, AND EAR HOSPITAL ; LATE PRESIDENT OF THE BRITISH LARYNGOLOGICAL ASSOCIATION ; CORRESPONDING FELLOW OF THE AMERICAN LARYNGOLOGICAL ASSOCIATION^ A utkor of "the throat and NOSE, AND THEIR DISEASES," ETC. ETC. ILLUSTRATED BY THE AUTHOR. LONDON : BAILLIERE, TINDALL, & COX. Philadelphia : J. B. LIPPINCOTT COMPANY. i89S- {J J2.,<%A>A,a. lcsA>~«,«jMi PRINTED BY SCOTT AND FERGUSON AND BURNESS AND COMPANY, 14, 16, -AND 18 CLYDE STREET, EDINBURGH. ^| O'^S 689 PREFACE. The subject of Diphtheria has been one of deep interest to me since the days of my pupilage, and has occupied active attention in each of the four editions of my systematic work on Diseases of the Throat as they have appeared at intervals since 1878. The present essay is based mainly on a course of lectures recently delivered, for the purpose of establishing a landmark at an important era in the history of diphtheria, and of emphasising the desirability of assimilating the teachings of bacteriology to the purposes of practical medicine. In other words, to indicate the necessity for the scientific expert and the clinician to work together as colleagues, and not as rivals. It must be thankfully conceded that clinical observations frequently gain additional confirmation, not infrequently a new significance, and even in a few instances coCTCction, when ex- amined by the light of bacteriological science. On the other hand, it is suggested that an undue tendency has arisen to evolve all the essential elements of diphtheria and of some other diseases — etiology, diagnosis, pathology, prognosis, and even treatment — from material afforded by animal experiments, the culture tube, microscope, and retort, and to ignore the value of bedside evidence, however authoritatively expounded, and how- ever long held as an article of faith, whenever it cannot be brought into exact harmony with the latest bacteriological utterance. vi PREFACE. But the value of all facts acquired in the laboratory must of necessity depend on their ability to stand the crucial test of bed- side application ; because, whatever the source of information, the saving of human life should always constitute the paramount object of all professors of the healing art. Whether I have been successful in laying down correctly the lines of a safe middle course, the following pages must testify ; that, at any rate, is the aim of this attempt. Every endeavour has been made to give the latest views on each separate branch of this vast subject, and for this purpose the opinions of recognised authorities are largely quoted. It is not, however, for a moment suggested that this essay is to be accepted as in any degree exhaustive. With the mass of literature and information at command, that were a task almost sufficient for a lifetime. It is a pleasurable duty to thankfully acknowledge the oppor- tunities afforded by the Metropolitan Asylums' Board to follow the course of Diphtheria, as exhibited and treated according to modern views, in one of their hospitals, in a manner and to an extent that is impossible for one who, in consulting practice, but too often sees a case when the malady is so far advanced that the patient is practically beyond hope of recovery. To Dr. Gayton, Superintendent of the North-Western Fever Hospital, whose wards I have attended, I owe an especial debt of gratitude for the great liberality with which he has permitted me to acquire information, for his zeal and co-operation in my work, and for much wise counsel, the outcome of a unique experience, which cannot fail to give value to a large portion of what I have to say. To the Clinical .Eesearch Association I am indebted for the PREFACE. vii great trouble taken with the bacteriological examination of the cultures I have made, and for the excellent microscopic slides which have enabled me to secure such characteristic photo-micro- graphs. These have been obtained at great pains, but with fully- compensatory results, by Mr. Lees Curtis, of Messrs. Baker & Co., under my personal supervision, with the more than capable aid of my assistant, Dr. HoUoway, who is an expert with microscope, camera, and lantern. The photo-micrographs have been " processed " with great exactitude by Mr. Carl Hentschel, and my own drawings have been very faithfully rendered by- Messrs. Scott & Ferguson of Edinburgh, to whom my thanks are also due for the careful printing of a book requiring so many diverse qualifications for the successful achievement of its production. 15 Mansfield Street, -W-., Jwae. 1895. CONTENTS. PAGE DEFINITION AND SYNOPSIS, 1 CHAPTER I. HISTORY OF DIPHTHERIA, 3 CHAPTEE II. ETIOLOGY, 11 Peemsposikg causes, 12 ; Geographical, 12 ; Causes of origin in sparse districts, 14 ; Of dissemination, 17 ; Geology, 18 ; Rainfall, 19 ; Season, 21 ; Domestic surroundings, 22 ; Insanitation and polluted water, 23 ; Infected milk supply, 24 ; Accumulations of organic and other refuse, 26 ; Tabular abstract of outbreaks, 28 ; Preceding or concurrent epidemics, 30 ; Scarlet fever, 30 ; Measles, 30 ; Smallpox, 31 ; Typhoid fever, 32 ; Chiokenpox, 33 ; Endemic sore throat, 33 ; Constitutional predisposition, 33 ; Mouth-breathing, 33 ; Enlarged tonsils and adenoid vegetations, 34 ; Decayed and badly kept teeth, 36 ; Tuberculous glands, 36 ; Age, 37 ; luooulability, 37 ; Contagion and dissemination, 38 ; In hospitals, 38 ; By school influence, 39. CHAPTER III. ETIOLOGY — Oontlnucd. The Bactekiolooy of Diphtheeia and its Associates, . . 41 Discovery of Bacillus by Klebs and Loeffler, 41 ; Subdivisions of Diphtheria, 44 ; The Klebs-LoefiBer bacillus, 46 ; Diplococcus, 48 ; " Brisou " coccus, 49; Staphylococcus, 50; Streptococcus, 50; Other coccal organisms, 51 ; " Pseudo-diphtheria " bacillus, otherwise the attenuated or non-virulent, 52. CHAPTER IV. ETIOLOGY — Continued. The toxic peoduots of the Diphtheeia bacillus and its Associates, . 58 Author's view, 58 ; Method of obtaining, 59 ; Nature of, 61 ; Action of, 64 ; The albumoses, 64 ; The organic acid, 66 ; Influence of associ- ated cocci, 66. CONTENTS. CHAPTER V. PAGE 67 PATHOLOGY. Morbid Anatomy of Diphthkeia and its Associates, Terminology, 67 ; General effects of diphtheria on system, 68 ; Micro- scopic structure of diphtherial membrane, 70 ; Of pseudo-diphtherial membrane, 71. CHAPTER VI. BACTERIOLOGICAL DIAGNOSIS OF DIPHTHERIA AND ITS ASSOCIATES, . 73 Method 1, Coverglass, 74 ; Method 2, Streak cultures giving negative diagnosis, 76 ; Method 3, ditto, giving positive naked-eye diagnosis, 78; Method 4, ditto, giving evidence of associated organisms, 78 ; Method 5, Microscopical examination, giving positive diagnosis, 80 ; Method 6, Subcultures and experimental test of virulence, 80 ; Classifioation according to organisms, 81 ; Table of clinical and bacteriological diagnosis, 82. CHAPTER VII. THE CLINICAL DIAGNOSIS OF DIPHTHERIA AND ITS AS- SOCIATES, . . 84 Preliminary questions, 86 ; Incubation, 86 ; Prodromata, 87 ; Tempera- ture, 88 ; Pulse, 89 ; Adenitis, 89 ; Albuminuria and other renal com- plications, 90 ; Perversion of special senses, 90 ; Site of membrane, 91 ; Clinical appearances of membrane in pure diphtheria, 92 ; In complex diphtheria, 95 ; In pseudo-diphtheria, 95 ; Differential diagnosis from scarlet fever, 96 ; Prom measles, 97 ; Prom whooping-cough, 98 ; Typhoid, 98 ; Smallpox, 99 ; Typhus, 100 ; Chiokenpox, rotheln, and mumps, 100 ; Tonsillitis, 100 ; Aphtha, herpes, membranous sore throat, pharyngeal erysipelas, and septic sore throat, 101. CHAPTER VIII. RECORD OP ILLUSTRATIVE CASES OF DIPHTHERIA AND ITS ASSOCIATES, . . .102 Class I., Bacillus diphtheriEe, 102 ; Cases 1, 2, 3, 4 — 103 ; Class II., Bacillus diphtherise with streptococcus — cases 5, 6, 7, 8 — 110 ; Class III., Bacillus diphtherias with streptococcus and staphylococcus — cases 9, 10, 11, 12 — 116 ; Class IV., Bacillus diphtherise with streptococcus and diplococcus— case 13—120 ; Class V., Bacillus diphtherise with diplo- cocous — case 14 — 123 ; Class VI., Streptococcus — oases 15 and 16 124; Class VII., Streptococcus— case 17 — 126 ; Class VIII., Staphylococcus cases 18, 19, 20—127; Class IX., Staphylococcus and diplococcus— case 21—130; Class X., Diplococcus— case 22— 131 ; Class XI. , Diplococcus with mycelium— case 23—132 ; Class XII., Indeterminate— case 24— 134. CONTENTS. CHAPTER IX. PAGE THE ELEMENTS OF PROGNOSIS IN DIPHTHERIA, 136 Bacteriological prognosis, 137 ; Personnel of the patient, 139 ; Tables of mortality, 140 ; Age disposition, 144 ; Social status, domestic sur- roundings, &c., 144 ; Clinical character of the membrane, 145 ; Mortality according to site, 146 ; General condition and aspect, 147 ; Temperature, 148 ; Algidity, 148 ; Rigors, 149 ; Pulse, 149 ; Adenitis, 149 ; Complications of the vital functions : Cardiac, 150 ; Respiratory, 151; Renal, 152; Laryngeal, 153; CEsophagus, stomach, and intestines, 154 ; Anus and female genitals, 155 ; Neuroses : Motor and Sensory, 155 ; Reflex, 157 ; Date and mode of death, 158. CHAPTER X. THE TREATMENT OE DIPHTHERIA AND ITS ASSOCIATES, 160 Primary hygiene, 160 ; General and internal remedies, 161 ; Diet, 165 ; Alcohol, 165 ; Topical remedies, 166 ; Solvents of membrane, 167 ; Removal of membrane, 169 ; Washes and irrigations, 170 ; Gargles, 172 ; Summary, 172 ; Post-nasal diphtheria, 173 ; Nasal diphtheria, 173 ; Laryngeal extension, 174 ; Aural diphtheria — suppurative, 174 ; Ocular diphtheria, 175 ; External applications : Leiter's coil, poultices, &c., 176 ; Operative measures, 176 ; Removal of enlarged tonsils — elongated or thickened uvula in acute stage, 176 ; Removal of adenoids, 178. CHAPTER XL LARYNGO-TRACHEAL DIPHTHERIA— CROUP, 179 Definition and sub-divisions of, 179 ; Ascending croup, 179 ; Descend- ing croup, 180 ; Non-bacillary, 180 ; Traumatic, 182 ; Morbid anatomy of non-bacillary, 183 ; Symptoms, 183 ; Cough, 183 ; Pain, 184 ; Dyspnoea, 184 ; Diagnosis, 184 ; Laryngoscopio signs, 185 ; Cause of dyspnoea, 185 ; Complications, 186 ; Prognosis, course, and termination, 186 ; Treatment, 188 ; Atmosphere and vapour, 188 ; General, 189 ; Local, 190; Operative measures — intubation or tracheotomy ? 191. Tbacheotomy, 194 ; Indications for, 194 ; Mortality, 195 ; Early opera- tion advised, 195 ; Hints for its performance, 196 ; Anesthesia, 197 ; Chloroform preferable, 197 ; After-treatment, 198 ; Removal of mem- brane through tracheal opening, 198 ; Complications, 200. Intubation of the Lakynx, 200 ; Instruments, 201 ; Method of operat- ing, 203 ; Aid of laryngeal mirror advised, 205 ; After-treatment, 205 ; Dysphagia and its relief, 206. PAOIS 207 xii CONTENTS. CHAPTER XII. HYGIENE AND PE.OPHYLAXIS OF DIPHTHERIA, Isolation and personal care, 207 ; Disinfection of room during attack, 207 ; Precautions for nurses and attendants, 208 ; Bacteriological examination on recovery, 209 ; Duration of activity of bacillus, 209 ; Treatment during convalescence of patient and attendants, 211 ; Pre- cautions in case of fatal result, 211 ; Prophylaxis with regard to school attendance, 211 ; Systematised throat examination of school children, 212 ; For notifiable and non-notifiable diseases, 212 ; Surgical measures of prophylaxis against recurrence, 213 ; Disinfection of sick room on termination of case, 215 ; Importance of correcting sanitary defects, 216. CHAPTER XIII. FORMULA FOR REMEDIES IN DIPHTHERIA, 217 Internal remedies, 219 ; Topical remedies, 221 ; Staining solutions for microscopical preparations, 224 ; Articles of diet, 225. APPENDIX. THE SERUM TREATMENT OF DIPHTHERIA, 228 Prefatory note, 228 ; History, 230 ; Theory of Immunisation, 234 ; Preparation of the remedy, 234 ; Immunisation of the animal, 235 ; The serum, 236 ; Test of antitoxic power, 236 ; Theory of action, 237 ; Metohnikofi's view, 238 ; Indications for serum treatment, 239 ; Dosage, 239 ; Method of Procedure, 241 ; Results, 242 ; Comparative tables of, 243 ; (1) Mortality, actual, 244 — and as calculated for age periods, 245 ; (2) Mortality after deducting cases fatal within twenty-four hours of admission, 246 ; (3) Day of the disease on which treatment was com- menced, 246 ; (4) Prolongation of life in cases with fatal results, 247 ; (5) Site of the membrane, 248 ; (6) Day of treatment on which the membrane commenced to separate, 249 ; (7) Day on which the throat was declared free of membrane, 250 — Disappearance of bacilli, 251 ; (8) Temperature, 251 ; (9) The pulse, 252 ; (10) Skin eruptions and joint pains, 252 ; (11) Adenitis, 254 ; (12) Otorrhcea, 255 ; (13) Renal complications, (a) albuminuria, (6) urea, (c) phosphates, 255, (rf) anuria, 256, (c) nephritis, 257 ; (14) Cardiac failure, 259 ; (15) Other causes of death, 260 ; (16) Paralytic sequelae, 260 ; (17) General well-being during treatment and convalescence, 260 ; Action on the blood, 261 ; Conclusions, 262 ; As a prophylactic, 264. INDEX OF LITERARY REFERENCES, . 265 GENERAL INDEX, 266 DIPHTHERIA AND ITS ASSOCIATES. Diphtheria and its Associates. DEFINITION AND SYNOPSIS. Diphtheria is an acute infectious disease due to the presence of a specific micro-organism (the Klebs-Loeffler bacillus). 1. Diphtheria is to be considered as simple or pure when this specific bacillus constitutes the sole organism ; and it may then be termed simple bacillary diphtheria. 2. Diphtheria is to be considered complex or impiore when the bacillus is associated with other micro-organisms, which are chiefly cocci, and may, in these circumstances, be termed complex or cocco-bacillary diphtheria. 3. The term pseudo or false diphtheria represents an affection of the throat resembling diphtheria, but distinguished from either the simple or complex varieties by the conspicuous absence of the specific bacillus. It may thus be termed non-bacillary diphtheria. 4. The term pseudo-diphtheria has also been erroneously applied to an affection of the throat characterised by the presence of a bacillus identical with the Klebs-Loeffler in every respect save that of virulence. A preferable term would be non-virulent bacillary diphtheria. To avoid confusion, the terms " diphtheria," " diphtherial," and "diphtheric" will alone be employed in this Essay to designate the phenomena caused by the presence of the Klebs-Loeffler 2 DEFINITION AND SYNOPSIS. bacillus, whether present alone or in association with other micro-organisms. The morbid influence of diphtheria due to its microbic origin is manifested in three distinct directions, two of which are common to both the simple and the complex forms ; the third is an additional characteristic of the complex variety, and is the sole bacterial expression of non-bacillary diphtheria. First. The Inflammatory process, which is accompanied by an exudation of false membrane; this is almost invariably first deposited on the tonsils and fauces, which may constitute its sole site, but the exudation may extend upwards to the nares ; to the middle, or even the internal ear, by the Eustachian tubes, or downwards to the larynx and trachea, as far even as the minute bronchi. The specific membranous inflammation may, as a quite rare exception, commence in the nares or larynx; equally seldom is it limited to either situation ; and still less often does it extend to the ossophagus or stomach. Diphtheria occasionally attacks the conjunctiva, as well as wounds of the skin and abrasions of the mucous membranes of other parts than those already named. As a result of this inflan.matory process in the throat, death may occur from mechanical obstruction of the air passages. Secondly. The poisonous qualities and products of the bacillus cause systemic intoxication, which is manifested, first by rapid death due to paralysis of vital functions, and as a later mani- festation, in those who survive, by degenerative changes in the nerves and muscles. Thirdly. The presence of associated organisms, especially strep- tococci and staphylococci, is responsible for the occurrence of the characteristic phlegmonous and pyaemic processes. Finally. Pseudo, false, or non-bacillary diphtheria is distin- guished by the absence of the specific toxaemia, though both the inflammatory and pyaemic processes may be exhibited in equal intensity with those of the true disease. CHAPTER I. HISTORY. 750 B.C. to A.D. 1884. The earlier accounts of diphtheria are of necessity confused, in that all the various forms of throat inflammation, characterised by the presence of false membranes, as well as others that were not, are included under the common but inexpressive terms of "Cynanche" and "Angina," and no purpose would be served by giving any detailed account of the views of earlier writers, or in attempting to harmonise their descriptions of diphtheria with our present knowledge. Suffice it to say that, from so far back as seven or eight hundred years before the Christian era, authors, whose number is legion, of every nationality, from D'Hanvantaee — an Indian physician, contemporary with Pythagoras — on- wards, have described, under various names, an affection of the throat, which can be interpreted to bear a more or less complete resemblance to diphtheria as we at the present time recognise it. Those who are interested in pursuing their studies in the bibliography of diphtheria may be referred to the writings of Bretonneau (1823-1855), of Deslandes (1827), Fuchs (1828), Headlam Gkeenhow (1860), Jacobi (1877), Eauchfuss (1878), MOEELL Mackenzie (1879), and Euault (1892), each of whom has contributed interesting and curious historical details with a completeness which it would be difficult to emulate and impossible to excel. The following are a few of those whose writings stand out as in any degree original or of prominent merit : — 4 DIPHTHERIA. AscLEPiADES (100 B.C.). The first to recommend laryngotomy. - Aeet^us, flourishing in the second half of the first century, gave descriptions of the objective appearances of the disease, which would almost apply to it at the present day. Aetius, of Mesopotamia, in the sixth century, pointed out the danger of tearing away the false membrane; and then, after a long interval, comes — Baillou, who, in 1576, recorded the occurrence of an ortho- pnceic affection of the throat, undoubtedly diphtheria, though con- sidered by Bretonneau to be descriptive rather of false croup — otherwise non-diphtherial laryngitis. Passing over numerous contributions from Italy, Spain, Sweden, and Holland in the sixteenth and seventeenth centuries, and an excellent account of an epidemic in Cornwall, by Stare, in 1750, we come to the work of Feancis Home, a Scotch physician, who in 1765 gave, under the names of " suffocatio stridula " and " catarrhus suffocativis," what may fairly be called a classical account of croup, as it was then named, and as it is still termed by the French when the larynx and trachea are involved. Some practical monographs were written in America by Bard in 1789, and Archer in 1798, and we learn from Bretonneau and Morell Mackenzie, that it was from croup — the French synonym for laryngo-tracheal diphtheria — that the great George Washington died in 1799, though his death is ascribed by most lay biographers to laryngitis, supervening on exposure to a severe snow storm whilst riding round his farms. In 1807 the nephew of the first Napoleon died from diphtheria at the Hague, within a few weeks of his father Louis, the brother of Napoleon, being invested as King of Holland. As a result of these disasters the Emperor offered a substantial prize for the essay which should give the fullest information "how best to arrest the progress of croup and its inroads.'' Other relatives of Buonaparte, amongst them the unha,ppy Empress Josephine and her grandchild, were later attacked, and succumbed. We learn that no less than eighty-three memoirs were sent in HISTORY. 5 for adjudication, and that the prize was divided between two of tlie competitors — Jurine of Geneva, and Albees of Bremen. Nothing could more forcibly demonstrate the great lack of information which then generally obtained as to the disease than a consideration of the opinions and the methods of treatment enunciated by these authors, but to quote from their writings would be only " to thrice slay the slain.'' It was reserved for Brbtonneau of Tours, — in his famous work, entitled " Brs inflammations spiciales die tissu muquetw," which, written in 1821, was not published till 1826, — to give a complete account of the disease as it had been exhibited during a terrible epidemic in the city in which he practised. This was followed by subsequent valuable memoirs on the same subject extending to the year 1855. Among the points of interest particularly brought out by this observer, was the minor position that diphtheria takes with regard both to contagion and gangrenous ulceration, as compared with scarlet fever and other diseases of this class, and his recognition of the systemic poisoning so characteristic of diphtheria, as evidenced by the occurrence of paralysis. He also drew attention to nasal diphtheria, to epidemic influenza as a predisposing cause, and to many other clinical features, not a few of which are brought under our notice from time to time as novelties. The vigour with which Bretonneau pursued his local applications of nitrate of silver — a mode of treatment first recommended by Mackenzie of Glasgow in 1825 — was probably responsible for the long delayed recognition of the essential importance of topical remedial measures in the scientific treatment of this disease. Bretonneau was also the first to administer mercury for this malady, which he did both by calomel given internally, and by inunctions with mercurial ointment. ISTot the least interesting and instructive of his experiences are the careful records of numerous necropsies which were performed under his personal supervision. Bretonneau's observations were generally confirmed by those of GUEKSANT (1835), who took special trouble to rescue the 6 DIPHTHERIA. nosography of diphtheria from the confusion into which it had fallen. Tkousseau directed his exceptional powers of clinical observa- tion to establishing a differential diagnosis between true and false diphtheria, especially that variety due to scarlet fever. His lectures on this subject have more than the usual charm of style which characterise his writings, since their delivery was largely prompted by the loss of more than one colleague and dear friend from the malady. Trousseau was one of the first to point out that the danger of this disease is manifested in two directions — first, by extension of the membrane to the air passages, and secondly, in an ataxo- adynamic form, in which the patient is carried off' without any such extension. He may also be said to have greatly assisted Bretonneau in establishing the operation of tracheotomy as the justifiable and even hopeful dernier ressort of diphtheria, and in gaining for it increased acceptance ; his indications for its adoption and the details of its performance giving us accurate data for guidance up to the present day. BouCHUT merits especial mention as a man of exceptional genius and ability, and as one who was indeed considerably in advance of his time ; for he it was who first practiced tubage* a procedure so condemned at that period as to fall into disuse for nearly a quarter of a century, until its successful revival and per- fection as intubation in 1880 by O'DwYER and other American physicians. Bouchut, recognising the primarily local nature of the disease, was also the first to remove hypertrophied tonsils during the acute stage of diphtheria, for the special purpose of preventing the downward extension of the membrane to the air passages. He recorded four cases of successful operation, in none of which did' the deposit re-form on the wounded surfaces. Daviot adopted the same measures, and recorded a case. He was also an advocate for forcible removal of the membrane o-ivinu' * Morell Mackenzie ascribes priority to Loiseaii {Bullet, de I'Acad. de Med. 18.''.7) HISTORY. it as his opinion " that the effects of cauterisation are never more certain than when we are operating on the surfaces denuded of their pseudo-membranes." Notice was directed to the frequency and importance of albuminuria in relation to diphtheria by Wade, Bouchut, and Empis, in 1858 ; their labours appearing to have been almost synchronous and independent. Of other writers of note in the middle of the present century we may name Virchow, who in 18-±'7 — in his special domain of pathological research — described, with his usual accuracy, the morbid anatomy of the parts affected by diphtheria as at that time recognised. In 1854, Von Geabfe was the first to note diphtheric con- junctivitis, and West in this country alluded to diphtheria as following measles, though at that time he had seen but little of it as a primary disease. We find subsequently the honoured names of several English physicians as authors of many more or less scattered contributions to the literature of this subject, of whom thereof Watson, Gull, WiLKS, Hakley, Lionel Beale, and Bukdon Saundeeson, may be mentioned. The great epidemic in England, which commenced in 1855, was believed to have been imported from Boulogne viA Folkestone. It raged almost without intermission until 1860, and it was only on its termination that English medical literature became enriched by contributions worthy of the theme. It is sufficient to name the statesmanlike reports to the Privy Council of Mr. (afterwards Sir John) Simon, and the volumes of Headlam Greenhow, Hillier, and, last but by no means least, Sir William Jenner, whose clinical lectures on diphtheria, published in 1861, are richly endowed with the keenness of perception, as well as the terseness and directness of utterance, which form the distinguishing features of all that has come from the pen of this eminent and revered teacher. Jenner originally believed that diphtheria — especially so far 8 DIPHTHERIA. as the throat manifestations are concerned — is altogether a different disease from scarlet fever, of which it was supposed to be a modification. Admitting, however, the probabihty that the two diseases are closely allied, he also wrote as follows : — " Are diphtheria and croup essentially the same disease ? I think not, because there is no evidence to show that croup is anything more than a local disease, that it is contagious,, that it occurs as a wide- spread epidemic, that it affects a large proportion of adults, that there is albumen in the urine, that symptoms of disordered innervation follow recovery from the primary affection. We must not confound diphtheritic exudations with diphtheria." It was in the spring of 1878 that I had published the first edition of my systematic work, in which I declared myself a non-identitist, and I have continued to do so in all the various editions that have since appeared, because of the teachings received in the early days of my pupilage, in 1858, spent in a district where the great English outbreak was notably accentuated. My principal, the late Mr. Brooks of Henley-on-Thames, never lost an opportunity of impressing on me that there was an old disease known as croup, which was capable of being distinguished from a new one called diphtheria, and of insisting on the diagnostic differences and characteristics of the two. Those early impressions were never effaced, nor did my interest in diphtheria ever wane ; while, with increased oppor- tunities of clinical observation, I became more than ever impressed with the truth of my early instruction — that is to say, T was never able to brin^ myself to admit that every acute membranous inflammation of the throat and larynx is a true diphtheria ; and, by a logical inference that every case requires the same treatment. I can particularly recall the pride I had felt that Sir William Jenner held the same view, and the feeling almost akin to shock which I experienced when, in 1875, he changed his opinion, and was quoted as giving his adhesion to the views of a Committee of the Eoyal Medico-Chirurgical Society, especially appointed "to in- vestigate the relations between membranous croup and diphtheria." HISTORY. 9 In 1878 this body collected a mass of highly interesting matter, embracing hospital statistics and the private records and opinions of general physicians and practitioners. The main conclusions arrived at by the Committee were in favour of considering laryngo- tracheal diphtheria and membranous laryngitis as identical, though careful perusal of the whole document brings out very strongly the fact that a large majority of those who contributed to the investigation by answering the Committee's circular of questions were so clear in their opinion that non-specific mem- branous laryngitis exists (and is met with in practice) as an entirely distinct disease from primary laryngo-tracheal diphtheria, that it was impossible for the Committee to speak more definitely. I feel constrained to add that some of the Committee's con- clusions, notably those regarding the influence of cold far se to produce croup, and on the question of contagion, appear to be in direct contradiction of the evidence which they published. The late Sir Gboegb Buekows, Professor Laycock, and Dr. Wilks, may be particularly named amongst those who gave testimony opposed to the report. Just about this time, the latter end of 1878, occurred the lamented death, from diphtheria, of the Peingess Alice, Grand Duchess of Hesse, a beloved and highly gifted daughter of our Sovereign. The disease was contracted shortly after nursing the Grand Duke and five of her children during an outbreak of the same malady, to which one — the Princess Marie — succumbed. Immediately afterwards. Sir Moeell Mackenzie published his scholarly monograph on diphtheria, a chapter in advance of his classical "Manual on Diseases of the Throat.'' The essay is a type of all that issued from Mackenzie in respect of fulness of detail, wealth and accuracy of reference, and grace of language, but unfortunately he gave unqualified assent to the diphtherial identity of all forms of membranous laryngitis, as did several other distinguished authors of systems and dic- tionaries of general medicine, though exceptions must be 10 DIPHTHERIA. credited to such eminent authorities as Si?' William Aitken, Tanner, Broadbent, F. Egberts, and Hilton Fagge. And so matters continued until 1884, a year made memorable by the discovery, or rather by the recognition and acceptance, of a specific organism of the disease, namely, the Klebs-Loeffler bacillus. This circumstance settled not only the question in favour of the non-identity of all forms of membranous inflam- mations of the upper air passages, but also that of the local origin of diphtheria. The events which led to this epoch-making circumstance, as well as to its further development, must be reserved. CHAPTEE II. ETIOLOGY. CLIMATE — SOIL — SANITATION — PRECEDING OR CONCURRENT EPIDEMICS — CONSTITUTIONAL STATES — MODES OF DISSEMINATION. Logically, the etiology of diphtheria might he comprised in a description of its specific organism, with its local manifestations and its systemic effects, and such has been the course pursued by those who are commonly described as scientists ; but important as it is that every detail in the life history of the bacillus, its congeners and associates, as well as their varieties, from the double point of view of culture ground and virulence, should be duly estimated, those who have to battle with the disease at the bedside, and 'also to prevent its extension, must go still further back, and seek for some measure of exactitude in first causes, as compared with those accepted in relation to the etiology of other specific diseases of zymotic origin. It has to be remembered that diphtheria may arise either epidemically, endemically, or sporadically. There can be little doubt, however, that receptivity to infection depends largely on some ill-defined though fairly well understood insanitary circum- stance of region, atmosphere, or individual ; and accepting this as our view, we shall proceed to discuss : — First. The predisposing causes of the origin of diphtheria, and some of the obvious agents by which the disease can be dis- seminated. SecoTidly. The diphtherial entity, in other words, the specific organism, its toxic products and effects, and other organisms which may be associated with it. 12 DIPHTHERIA. Testimony on the first division of our subject is as profuse as it is contradictory, being largely anecdotal and irresponsible. It has therefore appeared advisable to take, as the most reliable evidence, the reports w^hich have been made (45 in number) to the Local Government Board by various deputed inspectors, partly because the witnesses are experts, partly also because the reports have all been submitted to the revision of distinguished chiefs before publication, but mainly because there is a certain uniformity of method in their construction. They embrace particulars of all important outbreaks for the last twelve years, the first bearing "date 26th December 1882, and the last 27th November 1894. The tabular abstract of these reports appended to this section :will show at a glance the main features on which they are based, and brief comments will be given under each heading ; but before considering those of domestic and rather individual interest, a few words are necessary as to broader features which may influence the causation of prevalences. The Predisposing Causes. These require to be further subdivided into : — (a) Climatic and domestic surroundings. (6) Preceding or concurrent epidemics of other specific fevers, as well as the development of a pseudo-diphtheria into an attack of the true disease, (c) Constitutional predisposition. The Influence of Climate. Under this comprehensive heading may be included geographical distribution, geological conditions, the amount of the rainfall, and the infiuence of season. Geographical. — Dr. Thursfield was the first to demonstrate that the mortality from diphtheria is nearly three times greater in rural districts than in urban. He has also remarked that those condi- tions of soil which tend to promote fungoid growths, appear to ETIOLOGY. 13 favour the incidence and persistence of the disease. Dr. Longstaff, following the same line, has made some careful and valuable reports on the geographical distribution of diphtheria. Dividing England and Wales into eleven registration districts, he makes his comparison (1) in regard to the mean annual death-rate from diphtheria, (2) in regard to the density of population, and (3) in regard to the mean annual death-rate from all causes, which is taken for England and Wales as 100, so that the excess of each division is read off in percentages of the mean. Lastly, he divides the 26 years (1855-1880) included in his report into three different periods. The important question in relation to our present subject is that of the density of the population, and for the purposes of classifica- tion the districts are further subdivided into — (1) Dense districts.— Those in which there is less than one acre of surface to each person. (2) Medium districts, in which there is more than one acre, but less than two acres. (3) Sparse districts, in which there is more than two acres to each inhabitant. These investigations show that density of population cannot be considered as an important factor in the production of fatal diphtheria ; on the contrai'y, the malady is proved to be more fatal in the rural and sparsely populated districts, thus fully supporting Dr. Thursfield's earlier conclusions. It has been further demonstrated that "the geographical dis- tribution of other zymotic diseases is totally different from that of diphtheria. That summer diarrhoea is especially a disease of towns is a familiar fact to which attention has repeatedly been called by the Eegistrar-G-eneral. Measles is especially fatal in London. Scarlet fever is most common in the mining and manu- facturing counties," while diphtheria is manifested in these same manufacturing districts in very varying degrees of intensity. This fact still obtains, but it has undergone some degree of modification. Thus, in the first period, the relative mortality of 14 DIPHTHERIA. diphtheria in the different districts proves the malady to have been twice as fatal in sparse and rural areas as in large towns, while districts with medium density of population occupied a middle position. In the second period the results were less strik- ing, and in the third the differences were still less marked. Assuming the mortality of the dense districts as ].00, and strik- ing an average of the three periods, the result gives — Mortality in dense districts, 100 medium „ 118 sparse 151 A map accompanies Dr. Longstaff's interesting reports, in which the counties are tinted, so that the depth of colour is pro- portional to the mortality ; and this emphasises the circumstance that diphtheria has a strong predilection for scattered rural populations, and even for districts reputed to be exceptionally healthy as regards other infectious diseases. In each succeeding decade, however, the urban districts have been found to suffer more and more relatively to the rural. Two questions may therefore be asked — ■ 1. What are the predisposing causes which account for a greater frequency of diphtheria in sparsely populated districts ? 2. To what may we attribute the gradual increase of an urban prevalence which has led to the greater approach to equal mortality with that in sparse districts ? The first question may be further divided with regard to two other factors, (a) those of origin, and (6) those of dissemination. («) As to origin — Amongst other causes which may be sought for, primitive modes of life, the development of vegetable organisms in damp dwellings, defective and polluted water supplies, and lastly, frequent and close relation with animals in the farm yard cows, pigs, fowls, &c., have all been given a certain weight, and a close etiological relationship has been claimed, between outbreaks of diphtheria in the human subject and epidemics of certain diseases ETIOLOGY. 15 of animals, such as pleuro-pneumonia and foot and mouth disease, as well as with " diphtheria in fowls, pigeons, and cats.'' Notwithstanding that we somewhat anticipate the question of the diphtherial entity, this appears an appropriate place to con- sider briefly the so-called diphtheria of animals in relation to human infection. Loeflfler, for instance, in 1884 described a diphtheria of calves due to the " bacillus diphtherise vitulorum," but neither in its morphological or biological characters, nor in its pathogenesis, is their much similarity between this organism and that of diphtheria in the human subject. Much the same may be said as to the diphtheria or tuberculo- diphtheria of fowls and pigeons. There is no evidence to show that this disease is capable of conveying diphtheria to man, and Professor ISTocard, the well-known veterinary surgeon attached to the Pasteur Institute, most positively afl&rms that human diph- theria is entirely separate and distinct from that of fowls. Nevertheless, seeing that fowls, pigeons, and calves, as well as some domestic animals, are susceptible to the infection of human diphtheria, the possibility of a re-transmission of the disease to the human being cannot be denied and should not be overlooked. Dr. Herman of Cape Town, answering my inquiries, has always found the disease in proximity to " manurial heaps and vegetable deposits," or to "cow stables." He points out that diphtheria, which is rather frequent " up country," appears in isolated farms in the sheep and cattle districts, where the animals are often herded in kraals, and where decaying refuse is not only in prox- imity to the dwelling-houses, but also close enough to contaminate the water supply. Our own experience has long tended to confirm this view, first put forth in print by Eenshaw, that diphtheria is especially apt to be associated with the proximity to heaps made up of both animal and vegetable refuse. I have known three cases in which an outbreak of diphtheria in a household had been preceded by an attack in the families of i6 DIPHTHERIA. the coachman in adjoining stables. In another instance there was connection of the drainage from the stables with that of the house ; and lastly, I was consulted with regard to a case in which the probable predisposing cause was proximity to a very insanitary pigsty. With regard to stables, all medical superintendents of infectious fever hospitals would probably agree that diphtheria is very fre- quent among those who have to do with horses. Not only does this apply to those who live in stables, but to drivers and con- ductors of cabs, omnibuses, and tramcars. Nor does this associa- tion of diphtheria with stable workers appear to be much influenced by variations in excellence of stable sanitation. No doubt, since manure pits have been abolished, and the heaps have been cleared away more frequently than formerly, the sani- tary condition of mews is better than in former times ; but one fact is worthy of notice in this connection — namely, that in the last 15 or 20 years the old practice of exchanging manure for fresh straw from the farms has fallen into desuetude, and as straw is now the more valuable, it is used for a longer time, and conse- quently the manure is allowed to remain until it is in a much further advanced condition of decomposition than formerly. The following case, in which I was consulted by Dr. Poyntz Wright, medical officer of health for St. Neots, is a fair example of the infliience of country life in the origin of diphtheria : — A young lady, aged 24, had heen subject to " ulcerated throat " and lacunar tonsillitis ever since she had scarlatina, fifteen years previously. Four days before her attack, the patient had walked across a turnip-field which had recently been flooded. She experienced great nausea from the horrible stench which was exhaled, but continued her walk to a sewage-farm, where she gathered some moss from an osier-bed. On the following day a sharp sickle-shaped herring-bone lodged in the left tonsil, and in her endeavours to extract it broke off short. Sore throat com- menced two days later, and on the next — the fifth from her visit to the sewage-farm— membrane appeared. The exudation was strictly limited to the left side of the fauces, with the exception of one small patch of membrane on the right tonsil. On the sixth day there was complete paralysis of the velum on the left side, with paresis of the muscles on the right. A friend and other children of the same family who had been ETIOLOGY. 17 waUiing with her on the occasion noted were unattacked ; and with the exception of one (doubtful) case of diphtheria ten miles distant, the dis- trict was quite free from the disease. There can be little doubt that in this case the chronically in- flamed condition of the tonsils, and the consequent abeyance of their function of phagocyte - production, rendered the patient susceptible to the noxious influence of the probable microbic poison of the decaying turnips, and to possible germ emanations from the osier-bed at the sewage-farm, and that the wound from the herring-bone further prepared the throat to receive infection. The following curious circumstance is worth recording in this connection, though it has points of interest which apply to other considerations of etiology ; it has also an especial bearing on the prophylactic influence of antiseptic measures : — I was asked, in July 1885, to attend a young lady in conjunction with Mr. Henry Bury, of Whetstone. The patient was a tall, well-grown girl of 1 7, and of good constitution. She resided in the same house as, and was the constant and inseparable companion of, another young lady of the same age, but of delicate health, who had for some years been under my constant care on account of strumous ozsena, for the relief of which she diligently employed antiseptic applications in the shape of sprays, douches, and ointments. There were other cases of diphtheria in the adjoining stables and in the neighbourhood, but the exciting cause in the case under notice was believed to be the breathing of exhalations from the stagnant and foul water of a pond where the two girls had been amusing themselves catching tadpoles, &c. Now the stronger of the two had diphtheria very virulently, and the attack was followed by grave and protracted paralyses. The delicate girl, who was employing antiseptics, had a very high temperature for two or three days, and was prostrated ; but she exhibited no throat symptoms nor sequelse whatever. (5.) Dissemination. — While the foregoing causes may account for many an outbreak of diphtheria in rural districts, such as those referred to by Dr. Herman in isolated homesteads, it has been pointed out that the neighbourly inter-communication, which is the rule in villages, is infinitely more intimate and frequent than in large cities. This fact needs no elaboration; but interesting examples of its force are supplied in several of the Government Eeports, which are here tabulated. B iS DIPHTHERIA. The increased facilities of transit and means of communication between those living in the country and those residing in towns, and the aggregation of children in Board schools and in other similiar institutions, have doubtless their share in the gradual equalisation of mortality in rural and urban populations. Some of these will receive fuller consideration. But besides and beyond these circumstances there are questions relating to the sanita- tion of large towns and cities, in Iregard to which Dr. Corfield has suggestively expressed doubts as to whether many of the so-called improvements in drainage, disposal of sewage, and ventila- tion of sewers are really improvements after all, but this is again to somewhat anticipate. Geology. — According to Dr. Longstaff the greatest mortality from diphtheria has occurred in four especial districts, namely, Norfolk, Lincolnshire, North Yorks, and Sussex. If we compare the geological features of these areas with others in which similiar conditions of strata obtain, it cannot be contended that there are any conclusive data to be derived from a geological point of view, which can be held to exert an appreciable influence on the development or on the diffusion of diphtheria. And this conclusion is strengthened by a com- parison between counties such as Herts and Bucks, which possess similar geological features to those existing in Norfolk. While, however, the mortality ranges from 54 to 79 in the former two districts, in Norfolk it is 149 to 191. It will thus be seen that epidemics in our country have been very catholic in their distribution from both the geographical and the geological aspect. Nevertheless, our table would appear to justify the belief in a decided preference of diphtheria for a clay soil, an excess of diphtheria on argillaceous strata in the United Kingdom being evinced to the extent of 57-7 per cent. These figures bear out the opinion of Dr. Thorne Thorne that " where a surface soil is, by reason of its physical constitution and topo- graphical relations, such as to facilitate the retention of moisture and of organic refuse, and where a site of this character is, in ETIOLOGY. 19 addition, exposed to the influence of cold and wet winds, there you have conditions which do tend to the fostering and fatality of diphtheria, and also go to determine the specific quality of local sore-throat." Also that of Dr. Airy, who refers to " diphtheria in its favourite haunts on clayey soil," affirming that the " soil was in almost every case (inspected by him) more or less clayey and wet." Dr. Kelly also points out that " the mortality from diph- . theria is much higher on wet and retentive soils than on dry and pervious ones." Nor does it appear to make much difference whether the clay is on the surface or lies below a porous upper stratum such as gravel, green sand, sandstone, oolite, &c. ; for any such strata deposited on clay produce a water-logged con- dition, than which there can be none more favourable for the growth of the lower forms of vegetable life ; and this brings us to recognise that dampness of soil implies, even with the best laid schemes of drainage, a dampness of habitation, the specific connection of which with diphtheria Thursfield was one of the first to enforce. Diphtheria has been noticed to be more or less endemic in riverside villages, where the cottages are much enclosed by trees and covered by floral vegetation. Outbreaks of diphtheria have occasionally been manifested in bleak, exposed and cold situations, as on heaths and high elevations; but here probably a tendency to sore-throat from the action of keen winds has been an alternative predisponent of infection, to the more usual low type of inflammation resulting from damp. Rainfall. — The amount of rainfall differs to an appreciable degree in the United Kingdom, according to the geographical situation of any given locality. In the eastern counties the average is below 25 inches per annum ; in Westmoreland, Cumber- land, Wales, and the most elevated parts of Devonshire it may vary between 60 and 200 inches ; and in the remaining parts of England the average is usually between 30 and 40 inches yearly. Professor Eamsay gives the following averages for the amount of niPHTHERIA. rainfall per annum :— Cornwall, 37 to 54 inches ; Sussex, 26-3 to 29 inches; Norfolk, 24 to 25 inches. In the higher parts of Yorkshire, 51 to 56 inches. The rainfall in the western part of England and Wales is greater than that in the east, gradually becoming less as we pass from the S.W. to the S.E. areas, a fact which bears no relation to the areas where diphtheria is stated to be most prevalent. In view of these statistics, therefore, the relation between outbreaks of diphtheria and excessive rainfall is by no means evident, for, to take one more example, — while in Lancashire, the average rainfall is from 60 to 64 inches, the diphtheria mortality is as low as 54 to 79 ; in Norfolk, which has an average rainfall of 24 to 25 inches, the diphtheria mortality rises to 149 to 191. Oertel's remarks on aerial infection of diphtheria are worthy of quotation. He says : — " The possibihties of its transport are so many that they cannot always be shown even by the most care- ful inquiry. Transport by the atmosphere is rare, and one should only accept that explanation when really compelled to exclude all means of direct transport. Moreover, it cannot be denied that the sudden and simultaneous outbreak of many cases of diphtheria in one locality points rather to an infection either by direct conta.ct or by means of handling the same objects than to an infection by means of air and water. Por those epidemic and infectious diseases, for which we are compelled to admit the last-named mode of propagation, differ from diphtheria in that they are characterised by a gradual spread of the epidemic, which epidemic proceeds from single cases." But we must consider that we are definitely required by the hygienic and sanitary aspect of the case to remember that the air and water may act as carriers of the virus. Not, of course, in the same sense as the air of a malaria-region may be the constant bearer of the malaria-poison, or a contaminated well may be the source of an epidemic of typhoid. In the case of diphtheria, air and water can only act in the sense of actually carrying the con- tagion from one person to another, just as clothing, cooking and ETIOLOGY. 21 other utensils, or even such things as victuals, bread, milk, furni- ture, ornaments, and wall-paper. All that has been said of the poison arising in damp houses and specially situated localities rests more on the knowledge that such places are especially apt for the development of all kinds of fungoid growth, than on any reason which would satisfy a more stringent inquiry. Season. The disease is certainly more frequent in cold damp weather, and in the months comprised from the fall of the year to the spring. It is especially prevalent during the months of October and November, when the atmospheric conditions are favourable to the development of fungoid germs, and to catarrhal inflammations generally ; but it cannot be denied that diphtheria occurs at any period of the year, and under very varying influences of wind and weather. Diphtheria is far more frequent in temperate than in tropical ehmates, but in the latter it is by no means unknown. An interesting example of the liability to draw false conclusions with regard to the influence of the weather on diseases of the throat, is afforded in a report issued by one of the London Medical Officers of Health for the summer quarter, 1893, in which belief was expressed that an increase which had been observed in cases of throat-inflammation of an insanitary type, consequent on long continued drought and heat, was referable, First, to the wind-carrying of dried pathogenic organisms in the form of dust, and Secondly, to the want of proper flushing of sewers. We were, however, enabled to show by figures compiled on a large scale, that it is not during dry weather that throat diseases of this character are most prevalent, but on the first occurrence of a light rainfall after a prolonged heat and drought. In other words, that the epidemic wave seems to be greatest when the first rainfalls, being but slight, are sufficient to stimulate the dry and comparatively inert organic matter to activity, and that the prevalence only diminishes or disappears with the thorough 22 DJPHTHERIA. flushing of the sewers, consequent on heavier and longer-con- tinued showers. Domestic Sukroundings. Those who are well read in the history of diphtheria, as it has appeared in England in the last 40 years, cannot but beiinpressed by the fact that the districts which have been invaded during the last 12 years — as shown by our table — representing such different characters of soil and climate as Norfolk, Sussex, and North Yorkshire, are in many instances the same as those which were most seriously aS'ected by the epidemic of 1855-60 ; and of several of these localities it may be said that they have never since been quite free. It is evidence of this kind which ha,s led to belief (probably misplaced or exaggerated) in the existence of some constant factor in the way of chmate or geological formation ; for, presumably, preventable causes have, at least in some instances, been corrected. We must therefore seek for some further cause than that of soil, and it is fair to suspect that in most cases a solution of the doubt would be found in variations in sanitary environment. In estimating the preponderating cause assigned to the various outbreaks enumerated in the table, one is forced, by a consideration of the data given, to arrive at the conclusion that the inferences drawn from these reports by the various inspectors — carefully worded as they are — are not always in consonance with the facts. And, as a result, it has become fashionable to ignore the import- ance of those conditions in regard to diphtheria which are held to be of etiological value in the case of all other zymotic diseases ; and to assign, somewhat fancifully in many instances, causes for the origin of an outbreak, which should be more properly con- sidered as causes of dissemination. Our contentions are : — (1) That insanitation is one of the strongest predisponents not only to "simple sore throats," membranous and non-mem- branous, but also to true diphtheria. ETIOLOGY. i3 (2) That in cases of diphtheria attributable to contagion or importation, the infection-element is highly influenced in its development by non-hygienic conditions of individual or local surrounding. And lastly, that such non-hygienic conditions are not only responsible for the development of diphtheria, but that they do unfavourably influence the gravity of an epidemic or of an indi- vidual case. For we find that in 42 out of the 45 Local Government Board reports — that is, in 93-3 per cent. — there were undeniable evidences of defective sanitation, although in 29 only, 644 per cent., is such a cause assigned by the medical inspector for the origin of the outbreak. The nature of the assigned causes of the inspectors and of the actual state of sanitation under the various headings for con- sideration may be classified as follows : — Cases due to Insanitation or Polluted Water, 29 Infected Milk Supply, 4 „ „ Contagion in Schools, &c., 11 Doubtful, 1 45 Tlie general condition of Drainage and Sewerage was : — Defective, or even absent, in 42 Good or fairly good in -■ And not imputed in 1 _45 Chief amongst insanitary causes are impurity of drinking water and milk, the taint of the last being, as will be presently shown, usually due to dilution with impure water or to cleansing of the pails with the same ; defective sewers, ill trapped drains leading to an escape of sewer gas, surface ventilation of main sewers, soakage of soil with sewage poison, and indeed all those conditions 24 DIPHTHERIA. considered favourable to the development of typhoid fever and scarlet fever, with which diphtheria has so many points of resemblance. Strong as is the evidence against a de novo origin of any of these infectious diseases, it is held by some as unnecessary that the poison arising from any of the causes named should invariably be that of diphtheria. Nevertheless, in all probability such is generally the case, and the discovery of a separate bacterium for each variety of infectious fever can only be a matter of time. In the cases assigned to Infected Milk we find that three epidemics out of the four were associated with grave defects in the drainage of the locality where the outbreak occurred; and, altogether, notwithstanding " anecdotal " evidence, it is doubtful if milk, independently of outside contamination, is by any means a frequent agent in the propagation of diphtheria. For in only one case in our table, JSTo. 16, that of Ealing in 1887, does it appear to have been the sole cause. Even here, although the inspector believed that there was " a very strong presumption that the milk distributed from the dairy in question did, somehow or other, have to do with the outbreak of diphtheria, there is nothing amounting to proof of this, and on the other side an explanation is wanted of a notable disproportion between the quantity of milk distributed by the suspected dairy, and the amount of diphtheria witnessed among its customers." To take another report, N"o. 4 in our table, which treats of an epidemic of diphtheria in Hendon in 1883, analysis of a " sample of milk from the particular dairy that came in question, and a sample of the pond water there used for farm and dairy purposes, failed to find any fault with the milk,'' while the water was " discovered to be fouled to a large extent by sewage matter, and to contain in abundance, animalculee which were visible to the naked eye." There was a complaint made of a " ropiness " in the milk, but this was not observed when it was drawn off in carefully washed ETIOLOGY. 25 glass vessels, nevertheless there is a tendency on the part of the inspector to impugn the milk rather than the water used to cleanse the pans and pails. With regard to defects of sewerage being responsible for this outbreak, as well as for a certain amount of endemicity in the district, the inspector writes, " upon this point I need only say that, given a sewer origin of diphtheria, the circumstances of the sewerage in Hendon are likely to foster it." The report (No. 3 in the table) on an outbreak which took place about the same time at Devonport, appears still more conclusive of secondary contamination of the milk as distinguished from impurity due to cow disease, as the following abstract from the report will show : — The residents at the milk shop — dairyman, wife, two sons, and a servant, all adults, were stated to have been in good health. Next door, however, a case of diphtheria had occurred recently. The houses were much enclosed, and a communication was proved to exist between the drains of the dairyman's house and the w.c. next door. The milk cans, instead of being drained dry, were wiped with cloths which hung in close proximity to these ill- ventilated drains. To make our position quite clear in this matter, it is necessary to refer to one more epidemic of diphtheria, namely, that which occurred in 1878 in Kilburn and St. John's Wood, but is not included in our table. The report referred to 264 cases, with 38 deaths, a mortality so disproportionately small as to prac- tically prove that but a small number, if any, of the cases were truly diphtherial. Sore throat was endemic in the district. All causes were set aside except that of sewers and drains, and these were found to be generally badly ventilated and inadequately flushed, with, in several instances, direct communication between cisterns and baths with the drains. There was also an obstruction in the main sewer and a backward flow. Notwithstanding all these facts, the reporter, although he did not deny that the " sewer defects " theory had some frimd facie justification, endeavoured to 26 DIPHTHERIA. prove that sewerage held at best' only a secondary and subordinate place in the causation. The evidence supporting the milk theory rested almost entirely on the statement of interested persons, and absolutely no testimony is afforded of any disease in the cattle. The foregoing facts, which could be amply corroborated by an examination of reports of other outbreaks attributed to infected milk, fail to carry conviction against this particular and valuable article of food. It must, however, be admitted that milk is a congenial soil for the growth of micro-organisms — the diphtheria bacillus included — at a low temperature, and therefore it cannot be denied that this fluid may become a medium of infection. But it has also to be noted that the bacillus when grown in milk loses many of its chief characteristics, or perhaps it would be more correct to say it assumes others peculiar to its culture medium. It probably undergoes degenerative changes with rapidity ; possibly these are due to the presence of lactic acid. In the eleven epidemics assigned to contagion and importa- tion, the whole were found to be associated with sanitary defects of some kind. In one case diphtheria was said to be endemic, and in addition, in six cases reported as mainly due to insanitation, dissemination by schools was also noted. Emanations from accumulations of organic and other refuse which were foul and offensive were reported in nineteen cases (42-2 per cent.), and the outbreaks were associated with scarlet fever, measles, enteric fever, or " simple sore-throat " in nine cases, otherwise to the extent of 20 per cent. In connection with foul emanations as a cause of diphtheria, it may be noted that the opinion has recently become prevalent that the ventilation of sewers on the street level, and the disposition of small children to play about the gully-holes, may in some measure be responsible for the increased prevalence of diphtheria in urban over rural districts, the converse having been formerly the case. ETIOLOGY. 27 It may be, as has recently been reported, that experiments fail to prove the presence of a bacillus in sewer gas, and we give every respect to Koch's statement that these microbes " cling to their moist bed," and " cannot pass spontaneously into the air from a moist surface." Nevertheless the every-day experience of practi- tioners of medicine is overwhelmingly in agreement with the direct connection between the inhalation of foul gases and the occurrence of diphtheria and other specific infectious diseases. However that may be, it appears as imperative on us to convey the ventilation pipes of public sewers above the level of ordinary respiration, as is admitted to be the case in relation to the ventila- tion of water-closets in private houses ; and it is worthy of note that certain cities in which ventilation of sewers is not employed, have been found to be singularly free from outbreaks of diphtheria. On the other hand, a case has been reported in which an epidemic in the suburbs appeared to be promptly checked after flushing sewers so ventilated with a powerful germicide solution. A medical officer of health in a large suburban district has recently expressed the opinion that the increase of diphtheria in urban communities has been consequent on the introduction of water-closets and the draiuing of houses into sewers ; he supports his contention by quoting from so powerful an authority as Dr. Vivian Poore. Nevertheless, the arguments which he employs tend rather to show that the connection between the two circumstances is due more to imperfections in the closets themselves and leakage in the drains than to the system. The accumulated evidence of the various insanitary conditions which is here tabulated, and has been reviewed at length, can hardly fail to convince the impartial observer, that (to quote Sir George Johnson) " not to recognise the frequent filth origin of diphtheria may in practice be as disastrous as to ignore its infec- tiousness." TABULAE ABSTRACT OF REPORTS TO THE LOCAL GOVERJ^-- No. Inspector. Date. District. Geological formation. Princijjal Cause Assigned. Dr Parsons Dr Airy Dr Parsons Mr W. H. Power Dr Airy Mr W. H. Power Dr Parsons Dr Parsons Dr Blaxall Mr R. D. Sweeting Mr R. D. Sweeting Dr Gresswell Mr R. D. Sweeting Dr Gresswell Mr W. H. Power Mr W. H. Power Dr Parsons Dr Airy Dr Parsons Dr Bruce Low Dr Airy Dr Blaxall Mr Spear Dr Bruce Low Mr Spear Dr Page Dr Airy Dr Ballard Mr Spear Dr Bruce Low Dr Parsons Mr Spear Dr Bruce Low Dr Parsons Mr Spear Dr Blaxall Dr Bruce Low Dr Bruce Low Dr Home Dr Home Mr R. D. Sweeting Dr Wheaton Dr Evan Evans MrT.W.Thompson Dr Bruce Low Dec. 26, 1882 Jan. 23, 1883 Feb. 1, 1883 Apr. 5, 1883 Aug. 20, 1883 Mar. 8, 1884 Mar. 24, 1884 May 12, 1884 May 15, 1884 Jun. 29, 18S5 Aug. 3, 1885 Aug. 7, 1885 Aug. 29, 1885 Apr. 2, 1886 Apr. 7, 1887 May 31, 1887 Aug. 4, 1887 Aug. 12, 1887 Mar. 7, 1888 Apr. 23, 1888 July 3, 1888 Sep. 4, 188S Oct. 26, 1888 Oct. 31, 1888 Dec. 5, 1888 Dec. 8, 1888 Dec. 12, 1888 Feb. 18, 1880 Apr. 23, 1889 July 9, 1889 Sep. 2, 1889 Sep. 6, 1889 Dec. 2, 1889 Dec. 21, 1889 Mar. 29, 1890 Apr. 1, 1890 July 21, 1890 Sep. 8, 1890 July 10, 1893 Oct. 28, 1893 Dec. 11, 1893 Mar. 30, 1894 Apr. 27, 1894 Nov. 22, 189t Nov. 27, 1894 Gedney Drove End (Norfolk) Coggeshall (Essex) Devonport (Devon) Hendon (Middlesex) Great Dunniow (Essex) Ticl) marsh (North- ampton) Hambledon (Hants) Eversholt (Beds) Kingsclere (Hants) Cheshunt (Herts) Kempston (Beds) Glanford-Brigg (Lines) Great Ousebourne (Yorks) Beddington (Surrey) York Town and Cam- berley (Surrey) Ealing (Middlesex) Pwllheli (Carnarvon) Haslemere (Surrey) Wincanton (Somer- setshire) Enfield (Herts) Uckfield (Sussex) Mi dsomer- Norton (Somersetshire) Dingestow(Mon.) Ashbourne (Derby- shire) Aylesbury (Bucks) Berwick-on-Twee.l Norwich (Norfolk) Camelford (Corn- wall) Fareham (Hants) Halstead (Essex) Sowerby Bridge (Yorks) Penistone(W. Yorks) East Haddon (North- ampton) Leek (Staffordshire) Tredegar (Mon.) Berkhampstead (Herts) Barnstaple (North Devon) Malmesbury (Wilts) Derry hill (Wilts) U8k(Mon.) Alton (Hants) Hinkley (Warwick- shire) Rainham (Essex) Barnham Broom (Norfolk) Hastings (Sussex) Clay soil Gravel over clay Limestone and slate Clay Gravel Oolite and clay Chalk Green sand and clay Sandstone, chalk and clay Gravel and loam over clay Oxford clay Clay and chalk Sandstone and clay Sandy loam and chalk Bagshot sands Clay Limestone Sand and clay Lias clay Gravel and clay Sand and sand- stone Red marl and clay Clay and red sand- stone Red sandstone Oolite, Portland stone and clay Clay and sand- stone Gravel and chalk Sand and slate Sand, chalk and clay London clay and chalk * Sandstone Sandstone and clay Limestone and clay Sandstone and limestone Ferruginous sand- stone Chalk Sand and lime- stone Oxford clay Limestone Sandstone and limestone Chalk Clay and sand Sand and clay Boulder clay Green sand and clay Doubtful ; wind current suggested Probably polluted water Infected milk Infected milk In sanitation In sanitation Polluted water by sewage Contagion Contagion ; school influence Contagion ; school influence Contagion In sanitation Contagion Insanitation Infected milk Infected milk Insanitation Insanitation Insanitation Insanitation Contagion Insanitation Insanitation Insanitation Insanitation Insanitation Insanitation Insanitation Insanitation Contagion ; school influence Insanitation Insanitation Insanitation Insanitation Insanitation Insanitation Insanitation Insanitation Contagion ; school influence Insanitation Contagion ; school influence Contagion ; school influence Insanitation Insanitation Insanitation ; im- portation MENT BOARD ON OUTBREAKS OF DIPHTHERIA, 1882 to 1894. Drainage and Sewerage. Water Supply. No system ; cess- pools foul Defective Defective ; sewer gas Defective and in- sufficient Defective water- closets No sewerage at all Very bad No system of drainage No sewers Not imputed No drainage Very defective Defect! vfi Defective Atmosphere sew- age tainted Good Very defective Very defective Bad drains ; leak- age Defective Defective Very defective Absent or very bad Very defective Drains foul and defective Imperfect and de- fective Drains foul and defective Bad and neglected Drains foul ; very bad Fairly good Drains defective Foul and defective drainage Very defective Very defective No system what- ever Very defective Very bad Very defective Absent Imperfect Not adequate ' Very defective Defective Defective Defective Privies. Wells defective and polluted Polluted Good Pond water polluted with sewerage Wells polluted by sewerage Wells polluted Polluted in wells Good Exposed to pollution Liable to pollution Exposed to pollution Deficient and bad quality Polluted by surface matters Good Good Good Impurity suspected Exposed to pollution Wells polluted Unwholesome Sorae sources bad Exposed to pollution Polluted Liable to pollution ; often foul Fairly wholesome Inadequate Liable to pollution Polluted Polluted Fairly good Said to be pure Polluted Polluted Exposed to pollution Bad , Polluted Liable to pollution Polluted Wells foul Surface contamina- tion Said to be good Said to be pure Often polluted Often polluted Fairly good Refuse Accumulations. Remarks. Defective Too near dwellings Too near dwellings Foul and offensive Offensive and defec- tive Pail closet ; cesspit over-full Offensive cesspits Privies foul Defective Defective and foul Midden privies, un- cemented, &c., Defective Very Defective Defective and offen- sive Defective Faulty Bad Defective and primi- tive Foul Foul and offensive Insufficient and un- wholesome Offensive Foul and defective Foul and defective Defective closets and privies Foul and offensive Foul ; too near dwell- ings Foul and defective lusanitary Defective Foul and defective Foul and offensive primitive Foul and offensive Defective Closets defective Very defective ; often foul Defective Offensive vegetable matter Associated with wet season and poverty Contamination probably by foul wiping-cloths for milk cans Invaded houses were the best in district Possible connection noted with con- valescent scarlatina No evidence of "foreign importa- tion " Possible connection noted with scar- latina Mild scarlet fever and measles in spring Outbreak probably introduced by teacher Outbreak commenced with epidemic of " simple sore-throat" Otfensive refuse Personal communication leading to dissemination. Foul heaps Foul refuse abounds ; sewer emana- tions abundant Banks of mud and sewage sediment from river-cleansing No evidence available as to the source of infection Heaps of offensive organic refuse Formerly offensive house refuse Offensive domestic refuse Offensive refuse Outbreak followed on heat and drought Foul animal refuse Adults suffered disproportionately Foul emanations from abundant slaughter-houses and pig-styes Streets badly paved, unchannelled and unscavenged Ditto ditto Dissemination by schools also noted Heaps of highly offensive excrement Sporadic diphtheria long prevalent, and associated with enteric fever Very offensive smells from slaughter- houses Infection through school also noted Associated with enteric fever Outbreak aggravated by bad weather Associated with scarlet fever Defective to Buildings unfit for habitation (Abstr. from Brit. Med. Jour.) Refuse and pig-styes close dwellings Offensive refuse Accumulations not removed Diphtheria more or less endemic Manure hpaps near dwellings (Abstr. from Brit. Med. Jour.) Marked absence of sanitary pre- cautions Offensive offal refuse Offensive refuse heaps Diphtheria following measles Antecedent and concurrent scarlet fever; also small-pox 30 diphtheria. Preceding or Concurrent Epidemics. In the case of an epidemic of typhoid fever it is not difficult to determine the nature of the disease and the type in which it is exhibited by an examination of a few cases, but this is very different in a prevalence of diphtheria, which, beginning with a few cases of mild sore throat, may develop into an epidemic of the greatest malignancy, and during its rage cases may be exhibited in very varying degrees of intensity and in- fectiousness according to age and other individual circumstances. Moreover, a large proportion of outbreaks of diphtheria are pre- ceded by, or run concurrently with, epidemics of other specific fevers. These facts have been recently enforced by me as a reason why the proposals of the Local Government Board in regard to more exact examination of a few cases at the commence- ment of future epidemics of diphtheria cannot be placed on all-fours with those relating to typhoid fever and some other diseases, of which the cause has long been definitely ascertained and accepted. The frequency with which diphtheria is associated with scarlet fever is well known, but its relation to measles is by no means so generally recognised. Eyland mentions it in his Jacksonian Essay in 1837, and Dr. West in 1843. The following facts, taken from one of the most recent reports to the Local Govern- ment Board, are of interest in this connection. Mr. P. W. Thompson, reporting on an outbreak of diphtheria at Barnham Broom, near Norwich, ISTo. 44 on our list, and dated November 22nd, 1894, remarks : — " I find from my notes that, with one or two exceptions, all the children who, later, suffered from diphtheria, had about this time suffered from measles, which in some eases had been attended with considerable soreness and external swelling of the throat. The frequency with which diphtheria is found to coexist with or quickly follow in the wake of measles is such as to suggest a relationship between the two phenomena ; though the relationship may be of an indirect kind only, the measles increasing susceptibility to diphtheria, mainly, in all ETIOLOGY. 31 likelihood, by the damage inflicted on the mucous membrane of the throat.'' A lady who had read some communications which have appeared recently in the public press on this subject writes to me to the effect that five years ago her two little sons were attending a school in the west end of London. The eldest boy began with an attack of tonsilHtis, on which measles supervened. Several cases of measles had occurred among the pupils at the school, and had been followed in many instances by diphtheria, but this had not been notified by the head-master to the parents. The boy had a croupy cough and symptoms of dyspnoea, but with ill-developed rash ; he recovered, but his younger brother took the measles, with subsequent diphtheria of a malignant type, from which he died. His father was attacked by diphtheria, and also died. Two of the three trained nurses in attendance suffered from diphtheria, and were dangerously ill for some time : a Swiss servant also nearly died from the same cause ; and finally, a week later, the housemaid was attacked, and died. Five of the pupils attending the same school as this lady's sons died. A long investigation by experts failed to account for the outbreak. Eeverting to scarlet fever, Dr. Bruce Low, in a recent report (the last in our table) on the prevalence of diphtheria in Hastings, says " that the two diseases, in certain instances, were concurrent, and a number of persons who, on account of their suffering from scarlet fever, were sent to the borough sanatorium for isolation and treatment, were attacked by well-marked diphtheria during their convalescence," and several examples are given " of importa- tion of diphtheria into families by members returning home from the sanatorium after recovery from scarlatina, the patients in each instance not having been known to suffer from diphtheria during stay in hospital." This same report states that, six months previous to the final disappearance of diphtheria in the district, smallpox appeared, and that some of the patients who were in the sanatorium for treat- ment from scarlet fever were attacked with the disease. Neverthe- less, we find no mention of any case of diphtheria occurring in connection with the variola. Personal inquiry from Dr. Scarlyu Wilson, the medical officer of health, confirms the impression that during this outbreak of smallpox there was nothing in any of the patients to suggest co-existent diphtheria. 32 DIPHTHERIA. Information specially furnished to me as to the occurrence of diphtheria in connection with smallpox convinces me that it is most rare. Dr. William Gayton, who has had an experience of 15,000 cases of variola, states that he has never seen one; and Dr. Carnall, the present resident medical officer of the Smallpox Hospital, also informs me that the records are blank on the subject, and that, as smallpox is now seen, laryngeal complications are not common, except of a mild form. Nevertheless, three cases of reputed diphtheria after variola, which occurred in that institu- tion at the time of the outbreak of 1856-60, are related in Mr. (afterwards Sir John) Simon's second report to the Privy Council in 1860, on the authority of Mr. Marson, who was for many years superintendent of that hospital. The late Dr. Heslop of Birming- ham also reported a case of confluent smallpox, in which a diphtheritic exudation was observed. These cases having occurred before the days of bacteriology, cannot be accepted as undoubted examples of true diphtheria. Much the same may be said in regard to typhoid fever, which, being a disease often accompanied by stomatitis and faucitis of a pseudo-diphtheric character, is doubtless one offering a fertile soil for the implantation of the true diphtheria bacillus. The facts that outbreaks of diphtheria so often occur in districts where enteric fever is endemic, as well as the many points of parallelism in the clinical history of the two diseases, are significant. An epidemic of diphtheria has recently been reported at the Aubervilliers Hospital in Paris, which occurred among the patients attacked with chickenpox. They were completely isolated, so that contact with any other patient was impossible. Wot one of the chickenpox patients, when admitted into the hospital wards, exhibited false membrane in the throat. There was no case of diphtheria in the hospital. It was supposed that the diphtheria bacillus might possibly have been present in the saliva of one of the patients in the ward, and, moreover, that it might have been also possible that the individual who carried the bacillus may not ETIOLOGY. 33 have had diphtheria. Nor is this the only example which might be quoted. Where diphtheria is not associated with an actual specific fever a prevalence of some less serious form of infectious sore throat is a frequent feature, and this is so not only in our present tables ; for, referring to Sir John Simon's report to the Privy Council in 1859- 1860 on the earlier outbreaks, we find that of 29 epidemics of reputed diphtheria distributed over various parts of the country, endemic sore throat was noted in 27 cases, while in more than half there was a marked tendency to tonsillitis ; and finally, in 23 instances there was association with scarlet fever. Constitutional Predisposition. Sir William Jenner speaks strongly of " the influence of family constitution in favouring the occurrence and determining the end- ing of diphtheria," and quotes several cases of multiple attacks in the same household, " in all of which the hygienic conditions were good : there was nothing patently bad in regard of drainage, ven- tilation, overcrowding, water supply, food, or work. All the patients were in the middle rank of life, and resided in good-sized houses, and in fairly open situations. These facts, of course, speak strongly in favour of contagion, as well as in favour of the in- fluence of family constitution"; but even with this allowance, facts in support of Sir William Jenner's opinion as to the influence of constitution are not wanting. First and foremost, one must place that constitutional state which, running in families, tends to the development of those conditions which combine to produce what is known as mouth- breathing and their effects. In such a child the air, instead of being taken through the nostrils, where it is warmed, moistened, and filtered, goes direct to the throat — cold, dry, and germ- charged. Chief among the causes of obstruction of the naso-pharyngeal passages are enlargement of the faucial tonsils and hypertrophy 34 DIPHTHERIA. of Luschka's tonsil, otherwise known as adenoid vegetations ; and as results we find a strongly expressed " catarrhal " disposition along the whole upper respiratory tract, from a chronic cold in the head to frequent attacks of laryngitis and bronchitis. The well known impeded development of the chest walls in mouth- breathing children is also responsible for pulmonary disorders of a recognised type. My personal experience leads me to say that diphtheria hardly ever, if ever, occurs in a child under seven years of age who is not the subject of one or other of these forms of glandular overgrowth. It appears needless to enforce their tendency to abrogate the hygienic functions of the nose as the first avenue of respiration FlQ. 1. and to induce the marked deficiency in vitality and resisting power to contagion which are to be found in all such children. Indeed, this fact alone might account almost entirely for the varying death-rate fr'om diphtheria according to age ; since puberty is equally the period when tonsillar overgrowth has a natural tendency to reduction, and the mortality from diphtheria to markedly decrease. In many cases of diphtlieria in young adults tonsillar enlargement will be found to have persisted ; and it has been particularly noted in nurses who have taken the disease. The accompanying illustration (Fig. 1) is th(» tonsillar portrait of a nurse (aged 22) in an infectious fever hospital, taken some two months after she had passed through an attack of diphtheria. The tonsils were removed, at the ("entral Throat and Ear Hospital, ETIOLOGY. 35 with marked advantage to her general health, and she resumed her duties as a diphtheria nurse. Moreover, we have experience of several cases illustrating this point in a two-fold direction — namely, some in which removal of enlarged tonsils, and the consequent restoration of normal nasal respiration, have appeared to give a special immunity to the disease ; and others in which advice as to the removal of these glands and accompanying adenoids having been neglected, diph- theria has been specially fatal. Lest this statement should appear to be an exaggeration, it may be remarked that, in 1000 con- secutive cases of diphtheria specially tabulated for this essay, the exudation was reported to be limited to the tonsillar region in 666 cases, and that in only 8 of the 1000 was it not implicated. The fact of 99"2 per cent, of manifestations of diphtheria in this region is one the importance of which cannot be too strongly enforced. Not only is diphtheria highly contagious to those in attendance on the stricken patient, but its infecting properties may be re- tained for months, and even years, in tainted clothing, dwellings, and apartments. By what agency a medical attendant, a nurse, or other person in attendance, where every precaution against infection is taken, contracts diphtheria by merely breathing the same atmosphere as the patient — for only a few minutes, it may be — it is difficult to explain ; though doubtless it might be advanced that in most of such cases the conveyance of contagion is more material than is often admitted. There are, however, many isolated cases which can only be explained by supposing that germs from a diphtheric patch contaminate the breath. Eesearch into modern literature has failed to find any record of experiments in this direction, such as have been pursued with regard to the breath conveyance of the tubercle bacillus. Having, regard to the more superficial position of the diphtheria bacillus, there would be reasonable hope that an attempt would be successful. 36 DIPHTHERIA. In this connection the question might arise, Why, if the oral secretion form a suitable culture medium for the multiplication of the organisms (an essential feature in the infecting process), is it that the mucous covering of the tonsils and other lymphoid masses are most usually the areas invaded by the microbes ? In answer to this query, it may be pointed out that the tonsillar mucous membrane is more pervious to living organisms than any other, because of the diapedesis of leucocytes which is continually going on through it. Moreover, the crypts of the tonsils form quiet recesses for the incubation and subsequent germination of microbes, the whole constituting the " open wound " which Virchow has declared the tonsil to be. It is probable that in most instances where those exposed to infection have not contracted the disease, the leucocytes secreted by the tonsils have checked the germina- tion of the organisms. Where, on the other hand, the tonsils are diseased, phagocyte production is diminished, and such individuals are more liable to contract the disease when exposed to infection. Amongst the reports on outbreaks of diphtheria which have been abstracted, it has been remarked in one that a very large proportion of children attacked with diphtheria are the subjects of decayed and badly-kept teeth. This is probably true, but it is also true that this unhealthiness of the mouth and gums is a direct result of mouth-breathing, as is also the liability to enlarged tuberculous, or as they used to be called, strumous glands in the neck. It is interesting to note here that Trousseau had, so far back as 1843, devoted one of his lectures to "La BvpMMriU Gingivale et ses rapports avec le Croup (Laryngo-Tracheal Diphtheria)," especially as regards its transmission. Bretonneau, in his Fifth Memoir, expresses the belief that the Empress Josephine contracted the malady to which she succumbed " from the gingival diphtheria of Queen Hortense." Other constitutional predisponents have not been found in pon- derable proportion, but the following quotation from my book may not be inappropriate : — " No doubt, an anatomical explanation viz., the small and chink-like glottis of children — will account ETIOLOGY. 37 in some degree for the high infantile mortality, but it is also probable that the delicate organisations of the young are more affected than in the case of an adult by the virulence of the poison, be it a ptomaine or what not ; and I would once again repeat the opinion already frequently expressed, that in young children there is a greater tendency for inflammations of the air-passages to assume an exudative membranous type — thrush, plastic bronchitis, and non-specifio membranous laryngitis being diseases almost entirely confined to the period of childhood and adolescence." *''' These remarks would naturally lead to consideration of the etio- logical influence of age on diphtheria, but as this question is very fully treated in a later section (" The Elements of Prognosis"), no further allusion is required, except to remark that diphtheria is pre-eminently a disease in which susceptibility to infection is in direct proportion to the youth of the individual. Inoculability. Trousseau and others having failed in certain experiments made on themselves and on rabbits, the inoculability of diphtheria was at one time disputed. There is now, however, no doubt that the disease can be transmitted by the application of necrosing membrane to mucous or abraded cutaneous surfaces. The number of medical victims of the heroic, but none the less reprehensible practice of extracting membrane through tracheotomy tubes by their own lips instead of applying artificial suction is a striking testimony to its direct contagiousness. The failure of the experiments of Trousseau and others just alluded to can be readily explained by our own view ; first, that diphtheric contagium requires a suitable nidus, or soil, for its development ; and secondly, that all stages of the exudation are not equally active in their in- fective capability. Our first proposition will be readily conceded, and is proved in a measure by the happy miscarriage of Trousseau's rash experiments 38 DIPHTHERIA. on himself. The investigations of Eenshaw confirm the second, for the fact that many animals, especially the carnivora, can be infected by inoculation with a portion of diphtheric membrane has been abundantly proved ; and the author just named has conducted a series of highly interesting experiments, of which the following is a brief resumi. Portions of greyish-white membrane were mixed with the food of six cats, and in every case the disease was repro- duced with the characteristic lesions and symptoms. Experiments on fourteen cats with the younger yellowish -white membrane and with greyish membrane which had been soaked in Condy's fluid or in hydrochloric acid produced only negative results. Experiments on these lines have been repeated by other observers, and with similar results. Points of interest with regard to inoculation of, the specific organism and its toxic products will be considered more fully in the succeeding chapters. Contagion and Dissemination. As to ward contagion, given sufficient air-space and ventilation, with strict attention to the disinfection of a patient attacked, it is doubtful whether diphtheria is communicated from bed to bed — unless exceptionally. Of this one may assure himself by witnessing the course of events regarding the many patients who, having been admitted, on outside notification, to the diphtheria wards of our infectious fever hospitals, have been found not to be suffering from the disease for which they were received. Superintendents of these hospitals, of long experience, all agree that the liabihty of such patients to develop diphtheria is practically nil ; and the fact can- not fail to modify generally accepted views regarding the infectious- ness of the disease when uninfiuenced by insanitary surroundings. On the other hand, it is unfortunately quite frequent for nurses who come in contact with diphtheria patients to take the disease. In dwelling-houses the conditions are not quite the same as in a ETIOLOGY. 39 hospital, for we have, especially in the poor and lower middle-class, the probability of an insufficient amount of cubic air-space to begin with (it is 2000 cubic feet to each patient in the Metropolitan Asylums Board Hospitals) ; and the disposal and disinfection of all articles likely to be contaminated are either altogether neglected or inefficiently performed. This will account for such cases as infection from a pillow, from drinking vessels, from toys, picture- books, &e. It has also been noted that " isolation " in private houses even of good class is in many instances quite perfunctory. The first patient attacked being placed in a room with perhaps good air- space and every attention, recovers ; but a second or third, when attacked, is placed in the same room, without it having been pre- viously disinfected ; each additional patient diminishing the air- space of the chamber, and contaminating its contents, from ceiling, floor and walls, to every article of furniture, toilet, and food vessels. In the poorer class of houses, and especially in tenement build- ings, this factor of dissemination is enormously magnified, and the greatly increased numbers of this form of habitation may be one of the factors of the greater prevalence of diphtheria in urban dis- tricts in the last ten or fifteen years. As to "school influence," it cannot be logically claimed as responsible for the actual origin of the disease, although the frequent following of diphtheria on epidemics of sore throat or forms of pseudo-diphtheria is undoubted, and may be taken as an illustration of Dr. Thorne Thome's very reasonable theory of " the progressive power of infectiveness.'' There is, however, no evidence to show that these epidemic sore-throats take their origin in school aggregation. Indeed, the contrary has been proved by very carefully compiled statistics in a series of able articles from Mr. Biddle, who takes special note of the fact that mortality from diphtheria is hy far the greatest amongst children under five years of age, that is to say, luithin the age limit of compulsory school attend- ance, and also that there is a much greater and immediate rise in 40 DIPHTHERIA. diphtheria prevalences in schools on reassembling after holidays than in the middle of a term. — (Med. Press and Circ, Feb. 6, 1895, p. 153). The experience of all practitioners as to the portion of the term at which these and similar outbreaks are most apt to occur in private schools will agree with this pronouncement. Mr. Biddle .justly " contends that children for the most part incur greater risks at home or in the streets than they do at school, and that if proper care were taken, their attendance at school might be made available for discovering houses that had infectious cases in them, whether diphtheritic or otherwise." — {Lancet, Oct. 20, 1895, p. 342). Further considerations under this heading are rather suggestive of prophylaxis than as germane to causation. Sporadic, separate, or solitary cases of diphtheria, without obvious exposure to previous infection, are rare. Huebner's explanation that these cases arise through the influence of cold, inducing spasm of the superficial capillaries of the pharynx, to be followed by complete cessation of the circulation and diphtheric exudation, is certainly suggestive ; but in such a case the hygienic surroundings of the patient must presumably be favourable for the settling and development of bacterial germs. As these pages are going through the press, we add the following paragraph from the annual report of Dr. J. C. Thresh, Medical Officer of Health for the Maldon Eural Sanitary Authority for 1894 : — " There has been a very marked diminution in the cases of diphtheria notified. In previous years the great majority of those who suffered from diphtheria resided in Heybridge. In 1892, 26 out of 57 cases were reported from that parish; and in 1891, 90 out of 128. Yet out of these 116 cases there was only one death. Whether these were cases of true diphtheria or not " — most probably not — " their occurrence led to many improve- ments being made in the sanitary surroundings of the dwellings, and it is satisfactory to record that only a single case was notified from Heybridge during the past year.'' CHAPTEE III. ETIOLOGY— continued. THE BACTEKIOLOGY OF DIPHTHERIA AND OF ITS ASSOCIATES. Although the study of micro-organisms in relation to disease may be said to date from the year 1675, when Leeuwenhoeck gave an account of the larger species of bacteria, which he had found in animal excretions, the modern science of bacteriology is not yet forty years old, and it is less than half that time since the micro- organism of diphtheria was identified. A whole army of observers might be named in the history antecedent to this event, but in the forefront of pioneers in this region of discovery will always stand out the two names of Pasteur in France and Koch in Germany. It is generally stated that the bacillus of diphtheria was first described by Klebs of Zurich in 1883; but Professors Hamilton and Sternberg have drawn attention to its discovery by the same observer, and to publication of the fact at a Congress held at Wiesbaden, so far back as the year 1875. The circumstance appears to have attracted but little attention, notwithstanding that on examination of the original reference it is found that Klebs had announced at this date that he had not only detected the rod, but that he had also made an effort to cultivate it, and, as far as one can judge, successfully. To Klebs, therefore, the credit of having discovered this organism is undoubtedly due. But since he never definitely announced that he had been able to obtain pure cultures of it, it must be said that he failed in establishing its causal relationship to the disease. This was effected by Loefiler, who made pure cultures of the bacillus obtained from the throat membrane, and communicated 42 DIPHTHERIA. the disease to guinea-pigs and birds, by inoculating them on the pharynx, larynx, and other parts, with the products so obtained. On all these grounds, with the name of Klebs that of Loeffler will always be associated, because of his commendable and painstaking investigations of the specific taint-quality of the bacillus, and of his reticence in the announcement of his conclusions until he was « convinced of their accuracy. This he did in the year 1884. We will now brieHy recount the grounds for Loeffler's belief as to the identity of the bacillus of diphtheria with the causation of the disease, and some interesting corroborative experiments. I. It is found in all cases of imdouUed diphtheria. — In 1888 D'Espine demonstrated the presence of the bacillus in 14 cases of characteristic diphtheria, and during subsequent years numerous other observers, including Eoux and Yersin, and Von Hoffman, have abundantly confirmed this statement. It has also been demonstrated that it can frequently be found in the throats of convalescent patients. II. The bacillus can befoiind only in cases of undoubted diphtheria. — D'Espine when demonstrating the presence of the bacillus in the above mentioned 14 eases of true diphtheria, showed further, that it was absent in 24 cases of mild sore throat, which were clinically considered to be diphtheria. This observation has also been definitely confirmed. Doubts have, however, been recently expressed by Hansemann, Eiirst, and others, as to the universal presence of the bacillus in cases of true diphtheria; to which it may be replied, that the proportion of the cases in which the bacillus is not found is no larger than that in which it is found in the mouths of healthy individuals. With more sure methods of bacteriological ex- amination, the number of these is becoming smaller and smaller. III. The inoculation of pure cultures induces the disease in animals. — With regard to this point there was at first some difficulty, for although it was quite easy to produce a malady, with typical throat membrane, yet the fact that false membranes ETIOLOGY. 43 may be caused by scalding fluids, irritant poisons, or, as in one well known case, by Eau-de-Cologne, rendered the development of membranes an unreliable indication of the disease. The necessary proof, however, was supplied when Eoux and Yersin showed that, in a pigeon, paralysis came on three weeks after the pharynx had been inoculated with the bacillus, and when, further, the mem- brane had quite disappeared, and the bird was to all appearance well. They also showed that in rabbits the paralysis usually com- mences in the posterior extremities, and then gradually extends itself over the whole body, causing death by paralysis of the heart or respiratory apparatus. Welch and Abbott confirmed these observations by similar experiments on kittens. Another argument advanced against the specificity of the bacillus is in regard to exudation in the nostrils. Earely as is diphtheria confined to the nares — 0'2 per cent, in our 1000 cases — there is without doubt a form of rhinitis fibrinosa which, although containing the bacillus, is more chronic in its features than when the nasal diphtheria is associated with faucial or laryngeal exudation. The fact that the bacillus of diphtheria is not always to be found in plastic rhinitis only proves that here, as in the fauces, the exudation may be sometimes due to the diphtheria bacillus, and sometimes to the presence of micrococci. The discovery of the specific bacillus settled what threatened to be an endless controversy as to whether diphtheria is primarily a local or a general disease, in favour of the doctrine that it is in the first instance local. By recognition of its associated organisms we can distinguish the process changes which are caused by the bacillus, from the many complications which are no part of the disease, when exhibited in its pure form. We thus find it possible to separate cases of true diphtheria from the various conditions which clinically resemble it, whereas before the causal relationship of the Klebs-Loeffier bacillus to diphtheria was known, observers were obliged to rely upon clinical features only. Thus, not only our diagnosis and prognosis, but also our measures for 44 DIPHTHERIA. treatment and prophylaxis are now based on a more intelligent and rational foundation. Virchow and Von Eecklinghausen, in their early descriptions, distinguished three varieties of throat disease, in which changes in the mucous membrane occur. These they called catarrhal, fibrinous, and diphtheritic. Weigert further subdivided the fibrinous form into croupous and pseudo-diphtheritic. Either of these classifications, now that the bacillary origin of the disease is acknowledged, is open to many objections. A more useful one, and that here adopted, would be to separate the various forms of membranous sore throat, whether in fauces, nares, or larynx, into pure or simple, impure or complex, and pseudo or false diphtheria, according to the presence of the bacillus alone, to its presence in association with other bacteria, or to its absence altogether. And lastly, in relation to the existence of the bacillus in a non-virulent form, of which more anon. The final step was to prove that, although death in many cases of diphtheria resulted from mechanical obstruction, yet there remained a large majority in which the fatal result was due to systemic poisoning. This also was settled by Eoux and Yersin, who demonstrated that by inoculating animals with the liquid from filtered cultures from which all micro-organisms had been removed, all the diphtherial symptoms could be produced, with the exception of the membrane. These facts were confirmed and emphasised by Fraenkel and Brieger, Sidney Martin, Hankin, and others, and the last link between the etiology of diphtheria and the Klebs-Loeffler bacillus was thus forged. From the threefold aspect of diagnosis, prognosis, and treatment, the importance of an accurate recognition of the specific organism in any given case of membranous sore throat cannot be better emphasised than by the following figures, furnished by Hermann Biggs :— From May 4th, 1893, to May 4th, 1894, 5611 cases of suspected diphtheria were subjected to bacteriological examination in the ETIOLOGY. 45 laboratory of the Health Department of New York city. Sixty per cent, of these cases containing the specific Klebs-Loeffler bacillus were proved to be true diphtheria, while the large pro- portion of forty per cent., by its absence, were deemed to be false diphtheria. In a recent account by Drs. Washbourn and Goodall, of 80 cases admitted to an infectious fever hospital, certified to be suffering from diphtheria, only 61 cases were found to contain the bacillus. In 19 cases in which the bacillus was not found, 8 would not have been considered as diphtheria, even had not a bacteriological examination been made ; on the other hand, there were 11 non-diphtheric cases which were on clinical grounds diagnosed as diphtheria ; in all these the further progress of the cases fully bore out the bacteriological evidence of their non-specificity. In other words, an error in clinical diagnosis was made to the extent of 23-'75 per cent, of the whole 80 cases. Ten per cent, of these were corrected on admission by the Medical Superintendent of the Hospital, and of the remaining 61 cases admitted as true diphtheria' 18 per cent. — 13-5 of the whole 80 — received correction only after bacteriological examination .^ A third observation is that of Chaillou and Martin, who classify 99 cases of faucial angina, bacteriologically examined, as follows : — Pseudo-diphtheria (bacillus absent), 29, with no deaths. Pure diphtheria (bacillus only), 4-1, „ 10 „ Complex diphtheria (bacillus with cocci), or diphtheria with associations, 26, „ 18 1 It is only fair to state that the proportion of corrections in the clinical diagnosis by bacteriological examination varies at the different infectious fever hospitals of the same class. Thus at one, " of 61 cases all clinically diphtheria, the diphtheria bacillus was found in 55 {Lancet, Feb. 2nd, 1895, p. 305], a difference of 8 per cent," In another, of 45 consecutive cases, " 44 were certified by bacteriological examination to be true diphtheria," a mistaken diagnosis of only 2-2 per cent. [Medical Press and Circular Feb. 13th, 1895, p. 159.] 46 diphtheria. The Klebs-Loeffler Bacillus. This, the specific micro-organism of diphtheria, is a minute straight or slightly curved rod, measuring from 1| to 2 or 3 micro-millimetres in length, and 0'5 to 0'8 in thickness — that is to say, slightly longer but much broader than the bacillus of tubercle. The organisms occur either singly or in pairs (Fig. 2), frequently more or less parallel to each other (Fig. 3), or at an obtuse angle, like a circumflex accent, seldom end to end, and sometimes in small groups of three or four, often arranged fantastically, so as to bear close resemblance to letters of the alphabet, as V, M, N, X, Y, &c., or every variety of cuneiform character (Fig. 4) ; finally, the bacilli are sometimes, though rarely, arranged in chains (Fig. 4). Their outlines are not uniformly cylindrical, for a bulging is often seen at the ends. They show a characteristic segmentation of from two to five elements of protoplasm, and they stain in a peculiar way, one or other pole, often both, and sometimes patches of protoplasm between the poles being more deeply stained than the rest. The bacilli are said not to contain spores, but highly refracting particles may often be seen between the more deeply stained portions. Another reputed characteristic of these bacilli is that an appearance is occasionally witnessed (Fig. 5) as if the proto- plasm was shrinking away from the cell-wall, leaving a more or less regularly uncoloured or but lightly coloured space at the periphery. Three varieties of the bacilli are recognised according to their microscopical characters, namely, the long, the short, and the medium; they are also variously described according to their diameter as thick and thin. Their differences in length and calibre probably represent various stages or varying richness in the growth, for at present definite evidence is wanting to show that variations in the size of the bacilli, either in length or thick- ness, represent differences in the degree of their virulence. The tendency is towards attributing greater virulence to the loncy ■•';- / ..\ klf , , Ma > / » N-V ''( Fig. 2, Fig. 3. '4 Y< > %«''«»^ J >v « ■» ■» .^V f^ -^ / fi-\. 4% A* *vy^ /; J^ "*"**- ^■' ^"j;. / c^ Fig. 4. Fig. .5. :^g ^/ Ili^^^^^v^jU ^^- .', Fig. 6. ^5 v.^ Fig The BACILLU.S Diphtheele. 48 DIPHTHERIA. variety, since the bacilli examined during convalescence are almost invariably of the shorter kind. But the size of the bacilli, and also their method of staining, would appear to depend somewhat on the medium in which they are cultivated, cultures on glycerine-agar developing less fully and staining less characteristically than those grown on blood-serum. Fig. 7, representing a culture on milk from a specimen by Pro- fessor Klein, illustrates a still more striking difference in form, so different, indeed, that it would be well, if agreement were more general, to publish only cultures made on one particular medium. Of these, for all purposes of education and comparison, blood-serum is undoubtedly the best. Associated Micko-Oeganisms. The micro-organisms of clinical importance as associates of the diphtheria bacillus are mainly cocci. Of these we have — (1) Those arranged in pairs — diplococci. (2) „ „ groups — staphylococci. (3) „ „ chains — streptococci. As to the diplococcus, which is seen in the illustrations to be associated with streptococci (Figs. 8 and 9), it is sufficient to say that it is usually identified with the organism supposed, when encapsuled, to be specific of pneumonia. However, not only free diplococci, but those encapsuled, are to be found in membranous sore throats, and even in healthy ones, unaccompanied by pneu- monia, and in other diseases than pneumonia. The evidence at present is — to say the least — insufficient to support belief in the existence of a pseudo-diphtheria of a high grade, which is characterised solely by the presence of this organism. Our individual experience is, however, that throats in which diplococci are predominant, or are associated with other micro-organisms of greater importance, are "dirty" in character, and slow to clear away of pseudo-membrane. ETIOLOGY. 49 Some, importance has heen attached to a coccus (lesciilied hy Louis Maitin, a colleague of Iloux, and called liy liim, as must be admitted somewhat uuscientiticallv, "Brisou," after the name (jf the child in whom it was first " discovered." Martin names it as formino- one of the colonies which have i-esem- l)lance to those of diphtheria, and he .states that, in the case of the child in wdiom he fii'st witnessed it, tlie clinical features so singularly confused the diagnosis that the little patient was taken seven times to the diphtheria ward for a diphtlieria which he had not. The points of distinction on culture will he considered later, ,/ ' -n^^ ^ , / ...'•■ \ \.'- y ' ■ 'I \ , . , „ , „ . / \ , -♦ ■ . . \' ' . • ■• / \ •-■■■■■ :■; / l^ . Fig. S. Fig. 9. DiPLOCOCCI with STRErTOCOCCI RlGIDI. and it is sufficient here to refer to its microscopic features, which, as Martin says, should remove all doulits. He descrilies the appearance of this coccus as little points isolated or grouped two by two, but as the figure (No. 10) shows, they may occur in combinations of 3, 5, 7, or even 10. These cocci will be noticed in some of our own photo-micro- oraphs, and in them, as in Martin's illustration, they would appear to represent, to the ordinary eye, organisms hitherto considered as without importance and identical with those which are so D 50 DIPHTHERTA. frequently preHeiit in specimens nf secretion from the upper respiratory passages and in pulmonary sputa, while the larger groups are almost indistinguishalilc from small heaps of staphy- lococci. One is, therefore, somewhat at a loss to know why so much prominence has lieen given to so common and innocuous an organism, and it is to he li(i}ied that a lead, which has already lieen given in this country, to attach to it clinical importance will not 1-ie followed. Staphylococci, yillnis, Cifrciis, and Aviriis, and mainly the latter, in cases of mend)raiious sore throat, are geneivally associated with strepto- or dij)lococci, hut in certain cases, especially those attended Fifi. 10. — "Beisou" C'occu«. (/"((csmiyc, after Martin.) hy suppui-ation, they may represent the only micro-organism present. Instances are to he. seen in Fig. 11, and alsi;i in association with the liacillus and str(>ptococci in Fig. 1:^. Fraenkel speaks of another staphylococcus which does not li([uefy gelatine. Streptococci, when almie, generally ri'present a memliranous sore throat associa.ted witJi the exanthemata., of which scarlet fever is the must usual, Uiv this oi'ga.nism is almost invarial)Iy to ))e found in the throa.ts of sca,rla.tina.l patieid.s; not tliat we mean to ini],ly that this coccus is the specilic micro-organism of scai'let fe\-i'i', for tJiat at iireseiit is undiscovered; hut when found associated witli the liaeilhis of diphtheria, it is an almost >•* ■v" -^ I- ;*,»:;i \ .; .. sr Fig. 11. /A Fro. 12, X V ^ ^. V Fig. 13. X / ■%> • Fig. 14. 4^^ :■■■ Vi % '3 i .K*::t'^ ■ 'V ». • •• .»■. ■--'if-^ \>'-*'-Wr:^:^.; Fig. 1.5. i< ;? •?■ Fig. 16. 52 ^ DIPHTHERIA. unerring indication for grave prognosis, and represents an attack of diphtheria which has probably supervened on one or other of the acute specific fevers, probably scarlet fever or measles. Kurth was the first to point out that the arrangement of the streptococci bears some relation to their virulence, but the import- ance of this fact has been very generally overlooked, both in this country and in France. First in simplicity of order and mildness of indication are the Rigid, in which the chains are short and straight, as in Figs. 8 and 9, which represents the arrangement found in a case of insanitary tonsillitis. Next in severity are the Flexuous, in which the chains are curved or coiled, as notably exemplified in Figs. 13 and 14, which were both taken from a case of pseudo-diphtheria occurring during scarlet fever. Lastly comes the third form. Conglomerate, or, as we have ventured to term it, the Batallion arrangement, in which the chains are grouped in serried ranks, sometimes in parallelograms, sometimes in triangles, or in simple double file, one rank being longer than the next by one or more elements. These are found in the most virulent forms of complex diphtheria — namely, those which are implanted on a scarlatinal or rubeolar pseudo-diph- theria, and of which examples are to be seen in Figs. 12, 15, and 16. In Fig. 14 all three varieties are shown in the one slide. The illustration is from a drawing, not a photo-micrograph. Independently of these coecal organisms and of the specific bacilli, others are found. There is one which bears a strong resem- blance to the bacillus coll, and many unnamed and without significance. Lastly, it should be mentioned that, in some of the milder forms of throat inflammations allied to diphtheria, such, for example, as insanitary tonsillitis and non-bacillary lacunar inflammations, a mycelium may be present. Plant has recorded that, in some cases of non-diphtherial angina, he has found Miller's spirochoeta. ETIOLOGY. The " PsEUDO-JJu'iiTHEiiiA " Ba(;;illus. Smjgcdcd Synonym.— The. attenuated or non- virulent 1.)acillns. We have reserved to the last the consideration of a l.acillns difficult to distinguish from tlie genuine organism of diphtheria for in its method of growth, the formation of its colonies, and its microscopical appearance it is aljsolntely iilentical with the Klebs-Loeffler. Nor does it readily lose any of these charac- teristics on furtlier cultivation. The likeness of the two microbes consists not only in the appear- ■"%-.y ijK >-\4 -^, ?^^. %f- -.,^ *"/ ft'x^; H ^ n > *.« '- \ « ^ '^ < d /^j \f >». /*, 7i t- ■'. ' , .V 1' V if""* ',K * ■■/■.■» 'f Fig. 17. Fig. 18. ance of the bacilli separately, but in that fantastic alphabet arrange- ment, to which allusion has been made as a special feature in the identification of the true organism. Appended (Fig. 17) is a photo-micrograph of a beautiful example of this "pseudo-diph- theria " bacillus, as it has, in these days of exactitude, been some- what unfortunately named. The preparation was given to me 1)y my youug friend. Dr. Taylor Grant, who obtained it from a specimen of diphtherial membrane, afforded from the laboratory of Dr. Eoux. The specimen represents a pure culture, Ijut the original contained a few staphylococci. If one compares it with others of admitted 54 DIPHTHERIA. virulence, it is impossible to detect any real difference either in form or arrangement ; and any bacteriologist obtaining such a • result would not hesitate to give an opinion as to the true diphtherial character of the case from which it was taken. In point of fact, the only method of distinguishing this " pseudo- diphtheria bacillus " from that of the veritable Klebs-Loeffler organism is by an experimental observation of its non-toxic effects when introduced into the bodies of rabbits or guinea-pigs, that is to say, that although so similar in form, and responsible even to produce a membranous inflammation of the throat, it is non- virulent in the sense that it is incapable of producing toxaemia either in the person of the individual in whom it is found or by inoculation of lower animals. But such a protracted investigation as would establish this negative property is clearly quite impossible in ordinary practice, and a doubt must therefore naturally arise, in the light of the after history of at least some of the cases which, as the result of a bacteriological examination, have been declared to be true diphtheria, whether the specific organism has really not been of this benign character. For example, the case from which the Figure 4 was taken, that might be placed in comparison with that of the " pseudo " bacillus, was diagnosed by me to be one of lacunar tonsillitis, probably of insanitary origin. For the notes of this case, and the details of the appearances of the fauces on the occasion of first inspection and that presented two days later, which appeared to justify this view, the reader is referred to Case, 4, Chapter VIII. And since this patient made a rapid and complete recovery — without any paralytic sequela3 — there must still remain a doubt whether the diagnosis made at the bedside or that emanating from the bacterio- logical laboratory was correct. By a coincidence, since these words were written, this patient has again come under my care for the purpose of having his tonsils removed. Two days after the operation a curious exudation appeared on the wounded surfaces, which, on bacteriological examination, both by culture and microscope, exhibited all the characteristics ETIOLOGY. 55 of the pseudo-bacillus, as will be ascertained by the following report : — " Two cultures were made in this case, one from membrane sent in a culture tube, the other from membrane adhering to the swab. The cultures obtained were both of the same character, large, isolated, greyish white colonies, about twenty on the swab culture, about twelve in number on the other. " On microscopic examination bacilli of similar characters were obtained from each culture, accompanied by staphylococci. The bacilli were short and segmented, many being club-shaped and showing the character of the short variety of the bacillus diphtheriae. They are somewhat shorter than specimens of the Klebs-Loeffler bacillus usually obtained, and may be the pseudo- bacillus of Eoux and Yersin " (Fig. 18). A subculture showed colonies still more sparse and consisting mainly of cocci ; a further subculture failed to produce any development of the bacillus, the whole growth consisting of cocci. It is, therefore, to be presumed that in this case active cocci destroyed the attenuated bacilli. Dr. Sims Woodhead and other observers tell me that this particular specimen exhibits just the changes they are in the habit of witnessing in the examination of secretions of con- valescent patients. Judgment as to the category under which this "pseudo- diphtheria" bacillus should be classed is rendered all the more uncertain by the affirmed differences of opinion which exists among eminent observers in regard to the question whether it can or cannot be re-stimulated into virulence. All these circumstances tend to show that an error in clinical diagnosis cannot always be corrected by bacteriological methods, either so easily or so speedily as has been pronounced, and that the cases in which this difficulty may arise are precisely those in which a mistake by the clinician of experience would be most probable. Naturally, the worker in the laboratory is not satisfied unless S6 DIPHTHERIA. he can prove everything to a mathematical conclusion, but we, as clinicians, may be permitted to view this and several other bacteriological questions, at present undecided, by the light of common sense. Thus it appears only reasonable that as the specific organism of diphtheria is to be found on the floors, ceilings, walls, and furniture of rooms, through which many persons pass without infection, so also the organisms may be present in some throats which are non-receptive, or in those in- dividuals who are possessed of sufficient powers of resistance to either greatly modify or annihilate them. We also learn that no two horses are alike in their power of resistance to the action to the toxine of diphtheria when under- going inoculation for the purpose of immunisation. If, then, there is this variability of resistance in the man and the horse, why not — at any rate occasionally — in the rabbit or guinea-pig, the effects of experiments on which constitute the basis of argument ? We are told that the virulence of the true bacillus decreases at the end of a few weeks or months, and in process of time entirely disappears. Introduction of fresh bacilli into an attenuated culture will bring about a recrudescence of its toxic properties. If this can be effected in the laboratory we may understand the position which the so-called pseudo-bacillus holds in the estim- ation of various observers, one set believing it to be capable of regaining its toxic power, and the other that once innocuous it is incapable of ever again inflicting injury. As a corollary of Dr. Thorne Thome's theory of progressive development of infectiveness in the waxing of an epidemic, not only of diphtheria, but of other infectious diseases, it is within experience that there is a decrease in virulence as it wanes. It is suggested that it is in this aspect that the non-virulent bacillus is to be regarded, and it would be desirable before confusion has become more widely dissemuiated, that it should be renamed by some term which would deflnitely express its attenuated properties. ETIOLOGY. 57 Unless some such broad view, as is here suggested, be taken of this question, it would not be difficult to convert the " pseudo- bacillus " into a very Frankenstein, which would speedily destroy acceptance of the bacillary origin of diphtheria, as at present recognised. CHAPTER IV. ETWLOGY— continued. THE TOXIC PEODUCTS OF THE DIPHTHERIA BACILLUS AND ITS ASSOCIATES. The causal relation of the specific bacillus of diphtheria to the disease having been established, it still remained a moot point to what extent the manifestations of the malady could be attributed to the presence of the organism in the membrane until 1889, in which year all doubt was cleared up by experiments which scientifically determined the process, and established the fact that all the symptoms of diphtheria, except that of the development of membrane locally, are caused by the action of a definite poison. Chief among the workers in this interesting field of research are Eoux and Yersin, Hankin, Brieger and Fraenkel, Sidney Martin, and Klein, and this chapter will be devoted to relating as succinctly as possible the various conclusions at which these and other authors have arrived. Before proceeding further, however, the writer may be excused for recalling the circumstance that, in the interval between the discovery of the bacillus and that of its power to produce toxines, he had in 1887, on clinical grounds alone, ventured to promulgate the view, which was at the time adversely criticised, that the principal cause of death in diphtheria was a poisoning of the system by fermentative products of the special organism, express- ing the opinion, in the second edition of his book, in the following words : — "The tendency in this country at the present day, especially amongst younger and more advanced pathologists, is to accept ETIOLOGY. 59 provisionally the notion that diphtheria is at first a local disease, associated with the growth of micro-organisms on some mucous membrane or abraded spot. During the course of an epidemic it is supposed that spores enter, say, the mouth of an individual, and either do or do not find in the oral secretions of such individual, after being challenged by the scavenging leucocytes, a suitable culture medium. If the nidus be a favourable one the microbes germinate on the mucous membrane of, for example, some part of the pharynx or fauces ; as reproduction proceeds apace, the multi- plied organisms in the course of from two to eight days pass into the tissues ; and this invasion soon results in those pathological changes so characteristic of diphtheria, the false membrane. The life processes of the multiplying microbes are accompanied by fermentative changes, and the production of poisonous albumins and ptomaines, which pass into and contaminate the blood : systemic poisoning is thus accounted for.'' Of course I was in error in supposing that the specific poisons were ptomaines, but the suggestion to that effect was in accord- ance with the views then held, that all bacterial poisons were alkaloidal in their nature. Since then this specific property of such products has been definitely disproved. The following is the method employed by Roux and Yersin, who were the first to successfully obtain the toxines. The original broth culture of the bacillus is carefully filtered through porcelain to eliminate the microbes, and the filtrate is then precipitated by alcohol, dissolved in distilled water, and again extracted with pure alcohol ; the precipitate being dried in vacuo. By this process is obtained a white, or as some say, a yellowish powder, which is soluble in water. It is almost always neutral in reaction, but sometimes faintly acid. The powder is able to induce all the symptoms of diphtheria, except the membrane ; but its toxic potency is very much reduced by exposure to a comparatively low temperature — 58° C. for two hours — and is completely destroyed by the boiling temperature — 6o DIPHTHERIA. 100° C. for twenty minutes. The same effect is produced if the powder be long exposed to sunlight. The virulent bacillus renders its culture media acid in 24 to 48 hours ; the toxine, however, is only found in alkaline media, and is probably only soluble in alkalies. A free supply of oxygen has been found to promote the growth of the bacilli, to lead to early elaboration of the toxine, and to increase its virulence. The action of the oxygen prevents the media from becoming acid, and Ruffer has noticed that cultures freely exposed to air remain alkaline. Eoux and Yersin found further, that the bacilli, when inoculated into guinea-pigs, continued to multiply for from six to eight hours ; but that the animals frequently died, after the bacilli had either very much diminished in number, or had even quite disappeared. They kept cultures for five months, after which they found that although the bacilh were not so virulent as when the cultures were fresh, they were still fatal to the life of susceptible animals when introduced into them by inoculation. When the virulence of a culture has once been lost it cannot be regained, but if only weakened it can be re-stimulated into activity. Until recently it was held that the power of the toxine depends on the virulence of the bacilli, but this view has lately been disproved. Euault, for example, mentions that the toxic potency can be increased by the streptococcus of erysipelas, while Eoux, Chaillou, and Martin have all drawn attention to the increased gravity of diphtheria when associated with either streptococci or staphylococci; the author's personal experience is in accordance with their con- clusions. For, granted that in regard to these associated organisms, a large number are indifferent, and are simple wit- nesses, not playing any active t6U in the evolution of the disease, yet some are truly pathogenic, and appear to be capable of modifying the attack in variable degrees ; it may be in augmenting the virulence of the bacillus with which they are associated ; it may be in determining the secondary infections, which are super- added to the diphtherial intoxication; or perhaps in both these ETIOLOGY. 6i directions. Or it may indeed be possible that the diphtheria bacillus itself is capable of increasing the virulence of some of these micro-organisms, ordinarily inoffensive. Lastly, it may be permitted to suppose that certain micro-organisms may exist, which, if present in the throat at the same time as the bacillus, may be capable of attenuating its virulence, or of being attenu- ated by it. What is the exact chemical composition of this deadly poison remains at present undecided. According to Eoux and Yersin the toxine of diphtheria is of the nature of a diastase, and they give the following reasons for their opinion : — (1) It comports itself as to heat in the same way as a diastase ; that is to say, its power is gradually impaired, and finally destroyed above a certain temperature. Thus, although \. c.c. of a toxine solution is sufficient to kill a guinea-pig, 1 c.c. of the same solution, when heated for twelve hours at a temperature of 58° C, does not cause death in another of the same weight ; not that this dose is absolutely innocuous, for it is capable of killing small birds and setting up oedema in a guinea-pig at the site of injection. In the case of rabbits \ c.c. is fatal, but after heating for twenty minutes to a temperature of 100° C, the solution is quite harmless. (2) Like diastase, the toxine loses its toxic properties by the action of air, and by exposure to sunlight. (3) It is soluble in water, and insoluble in alcohol, the agent employed for its precipitation. (4) It has the same property as the diastases possess of adhering to precipitates. (5) Like diastases, the diphtheria toxine loses much of its activity if the medium is made acid. (6) Its energetic action in infinitesimal doses. Opposed to this view it has been urged that diphtheria toxine does not invert cane-sugar, or convert starch into glucose, nor does it convert albuminoids into peptones. These criticisms demon- 62 DIPHTHERIA. strate that the analogies of the diphtheria toxine with diastases are lacking in some important points. Fraenkel and Brieger believe the poison to be a tox-albumin, a view that was first promulgated by Hankin, but Wassermann and Prosskauer say that this tox-albumin is a mixture of the albumoses of the bouillon with the true toxine which, as noted by Eoux and Yersin, has such a strong tendency to adhere to pre- cipitates. Thoinot and Masselin have also pointed out that the product obtained by Eoux and Yersin is 100 times more toxic than the tox-albumin of Fraenkel and Brieger. Kanthack thinks the name tox-albumin is not a good one, because the albuminous or proteid matter can be removed from the poison, and he suggests that the products should rather be called toxines or tox- albuminoids. Until recently it was generally agreed by the majority of observers that the field of the bacillus of diphtheria is limited to the superficial parts of the membrane, and that the organism does not pass into the body ; for even when injected sub- cutaneously its development is confined to the site of inoculation. But Bulloch and Schmorl have found the Klebs-Loeffler microbe in the lymphatic glands — submaxillary, bronchial, and mesenteric — and even in the lymphatics themselves, in thirteen out of a total number of eighteen necropsies on children dead from diphtheria. In order to meet the objection that its presence in these situations might be considered to be a post-mortem occurrence, all the autopsies were made within five hours after death. Nevertheless, neither this circumstance nor the very rare occasions in which the bacillus has been found in distant organs can be held to weaken the fact that the Klebs-Loeffler organism is the specific source of the disease. That which has been proved to be effected by analysis in the laboratory and by experiments on animals, is probably what takes place during the course of the disease in the human subject. According to Sidney Martin, the microbe liberates a ferment or ETIOLOGY. 63 enzyme which is readily absorbed, and by its action on the proteids of the body, produces two poisonous substances, namely, cdhumoses and an organic acid, which are responsible by their action on the nervous system for all the constitutional symptoms — the fever, the cardio-respiratory asthenia, albuminuria, and paralyses. Many cases have been recorded of persons dying from the malady whose bodies were found, on ■post-mortem examination, to contain large quantities of the specific toxines; albeit in a considerable number of them, only a very small quantity of membrane had been present during life. Whence it is deduced that the source of all this poisonous material cannot be in the membrane itself, but that it is elaborated in the systems of those affected. This is rendered the more probable by the fact that large quantities of the poisons are found in such cases in the spleen. Chemical examination of the membrane, even in an early stage of its formation, proves it to be in course of digestion. It is also found to contain a poison which can produce results identical with those obtained from extracts of the blood and spleen of diphtheria patients when injected into animals ; but with this great difference uhat the poison is of a much more active and virulent character when derived from the membrane direct. The extract thus obtained, however, contains only minute quantities of the albumoses, and the rapidity of its fatal action is due probably to the enzyme which has been already mentioned as a product of the bacillus. Instances — unhappily too common— occur in practice, of rapidly fatal results, of which a satisfactory explanation can only be afforded by acceptance of the foregoing facts. The false membrane in diphtheria is one of the first results of the specific action of the bacillus. Being composed of fibrin, and moreover being in process of digestion, it constitutes a favourable medium for the growth and multiplication of the micro-organisms. Sternberg has noted that although a large number of pathogenic organisms are killed by exposure for ten minutes to a temperature 64 DIPHTHERIA. of 55° to 60" C, this comparatively low temperature has probably no destructive effect on any of the poisonous chemical products, which might be supposed to be the cause of infective virulence. Klein has recently gone a step further, and pointed out that " a definite distinction is to be drawn between the poisons which may be present in the bacteria themselves, and the poisonous sub- stances liberated or elaborated by these organisms." For he has shown that when certain micro-organisms are injected into the peritoneal cavities of rodents, they produce symptoms of poisoning without any of their metabolic products being present. Moreover, if the microbes, previous to their injection, are killed by heat at a temperature of 70° C, these dead bacteria in certain cases produce the same poisonous effects as the living organisms. Therefore, according to Klein, these micro-organisms must contain a poison in their own substance. The Action of the Toxines. The Albumoses. — When these products of the bacillary fer- ment are introduced into the animal body, they produce a local oedema, which subsides at the end of 36 hours, and is not followed by any destruction in the tissues, although some irregularity in temperature, and in the case of rabbits, distinct febrile conditions are found to follow the injection ; the blood becomes darkened and more fluid, and its coagulation is retarded. Larger doses produce a fatal result from paralysis or coma, but it is worthy of notice that equally noxious, but less rapidly fatal, results are obtained from small doses of the poison frequently administered. The paralysis may at its onset be rapidly fatal in its effects, or its progress may be slow and protracted ; in any case, it is always progressive. The hindrance to the coagulation of the blood offers a suggestive explanation of the delayed occurrence of the paralytic sequelte of diphtheria, even after all other symptoms of the disease have disappeared. ETIOLOGY. 6s The paralysis is manifested primarily and chiefly on the cardio- respiratory apparatus. The heart muscle is in all cases in an advanced degree of fatty degeneration. Sidney Martin has " not found any degeneration in the vagus nerve," and he suggests that the muscular degeneration may possibly depend on the altered condition of the blood, or, indeed, that the diphtheria albumoses may have a special action on the heart itself. Vincent of Paris and P. Meyer have found wide-spread paren- chymatous changes in the cardiac plexus in two cases of patients dying of heart failure during convalescence from diphtheria, in which the heart muscle was unaffected. The changes were exactly similiar to those found in the peripheral nerves in ordinary post- diphtherial paralysis. It is desirable that future observations should be directed to the further elucidation of this point. The voluntary muscles of the body are not by any means necessarily affected at the same time, those first impaired being those which of necessity are in constant use. In all cases im- pairment of activity of voluntary muscles is due to a degeneration of their nerve supply. Although there may be at first no apparent atrophy of the muscles, yet the body-weight of the animal decreases steadily. In diphtheric paralysis both the sensory and motor nerves are affected in a similar way, and the sympathetic system may be also involved, but, as would be expected, the part most affected in this case is the axis cylinder. The central nerve cells and ganglia in the spinal cord are most probably not the original site of the lesions which take place in the nerve trunks, for although morbid changes have been described by some pathologists in the anterior cornua of the cord, none have been discovered in those of the posterior cornua or sensory gangha, albeit both the motor and sensory nerves share in the degenerative process. The affection of the nerves must therefore be regarded as being entirely of a peripheral nature. The change commences in the white substance of Schwann, E 66 DIPHTHERIA. which undergoes rapid degeneration, breaking up and finally dis- appearing altogether. Following on this the axis cylinder may become ruptured — Seg^mental Neuritis — giving rise to well- marked Wallerian degeneration in the nerve fibres below the point of rupture. All the nerve fibres, however, may not be affected to the same extent, and some may still retain their power of con- veying nervous stimuli to the muscles which they innervate. The muscles which are deprived of nervous supply by the rupture of the axis cylinders in the nerve-trunks undergo a process of fatty degeneration and atrophy. The albumoses in diphtheria are therefore to be regarded as nerve poisons, which affect the peripheral nerves, and if ad- ministered in small and continued doses produce degeneration of the nerves, leading to both paralysis of motion and sensation. It is to be borne in mind that these paralyses may occur early in the acute stages of the disease, or in the later when they come under the head of sequelae. The Organic Acid. — This, the secondary bacillary poison, when injected into animals, produces fever to a slight extent, but no paralysis. If, however, an animal be treated with several doses at intervals, the heart post-mortem shows well-marked fatty degene- ration in the muscular elements, and some of the nerve fibres exhibit stages of degeneration similar to, but of a less degree than, that produced by very small doses of the albumoses. From these observations the organic acid must be regarded as a nerve poison of a much weaker nature than the albumoses. The presence of Associated Cocci is responsible for modifica- tions in the degree of virulence of the diphtherial toxines ; this is especially manifested in the difference in the character of the cardiac, pulmonary, renal, and other lesions. In point of fact, an infective process, due to the cocci, is superadded to the specific intoxication of the diphtherial poison. CHAPTER V. PATHOLOGY. MORBID ANATOMY OF DIPHTHERIA AND ITS ASSOCIATES. Diphtheria has been known under numerous names, such as Syriac Ulcer, Egyptian Throat, Garotillo, and other equally indistinctive terms, some of which have been mentioned in our brief history of the disease. It can hardly he said that the modern term is much better than those previously used. As is well known, the word Diphtheria originated with Breton- neau, who termed it diphtheritis, to represent an inflammatory disease of the throat, characterised by an exudation possessing the appearance of skin, parchment, or leather; though he was by no means the first to draw attention to this peculiar macro- scopic feature, and as has since been shown it is one that is by no means constant. Trousseau, justly recognising that the inflam- matory process of pure diphtheria is not of a high grade, suggested the term cliphtMrie, whence we get the word diphtheria. It is now known that from time to time cases are seen in which the exudation may be represented by the thinnest pellicles of deposit, and that false membrane may indeed be altogether absent, with no diminution of virulence or regularity of sequence of all the characteristic symptoms. The term Diphtheria is now accepted as representing a disease of which the pathognomonic and unalterable characteristic is the presence of the specific bacillus known as the Klebs-Loeffler. It is rather difficult in treating diphtheria in the practical manner at which this treatise aims, to satisfactorily consider all the various elements of its pathology under one chapter ; and it 68 DIPHTHERIA. has therefore appeared preferable to assign so much of it as relates to the bacteriological question to the special chapters on Etiology, and to relegate to that section which will embrace the Elements of Prognosis, consideration of those morbid changes which, occurring during the ordinary course of the disease or as com- plications and sequelae, can be diagnosed at the bedside and verified, it may be, on necropsy. Comparatively brief space will therefore be required for an account of the morbid anatomy which remains to be considered ; but without trespassing unduly on the proposed plan, there may be mentioned, in addition to those changes witnessed in the throat and air-passages, certain others to be detected on ;post-mm'tem examination of every subject dying from diphtheria. Thus, whatever the immediate cause of death, there is, independently of the localities which are the sites of the exuda- tion, a general congestion of the whole extent of the respiratory tract. The same applies to the digestive tract. The intestinal mucous membrane is generally hypersemic, and — according to Euault — there is marked hypertrophy of Peyer's patches in about half the cases. The spleen and liver are congested and enlarged, the latter often showing evidence of fatty degeneration. Equally there is general vascular dilatation, with inflammation of the lymphatic glands, and sometimes abscesses. Albeit the heart may appear healthy, the muscular fibres will, in almost every case, be found to have undergone more or less fatty degeneration. The kidneys especially partake in the general congestion. Whether all these changes are due to the toxic action of the diphtheria bacillus, or to that of superadded micro-organisms, these several lesions need not at present be further discussed. It is here sufficient to record them. The diphtherial membrane being indubitably the primary pathogenic offspring of the bacillus, calls for more special attention. The microscopic structure of diphtherial membrane is well shown in the excellent plate, for which we are indebted PATHOLOGY. 69 to Professor Hamilton. The exudation is poured out on to the surface of the mucous membrane, and, being rich in Deposit of DiPHTHEMA Bacilli on Surface of False Membrane. False Membbane. Mucosa. 3. - Lymph-cells in false membrane, sur- rounded by meshes of fibrin. Lymph-vessels, con- taining shed endo- thelium. - Mucous gland. Fig. 19.— Fbee Surface op Diphtheric Larynx ( x 350 Diams.) {After Hamilton.) By kind permission of Messrs. Maomillan & Co. 70 DIPHTHERIA. albiimen, coagulates into a tough, firm, aud elastic layer. This superficial layer is filled with buccal microbes — mostly indifferent — along with distinct little heaps of characteristic liacilli, some of which are also found imprisoned in the fibrin at a somewhat deeper level. ) • The bacillus of diphtheria is, in fact, found most abundantly in the superficial layers of the membrane ; it may also be yiresent in the deeper parts, but is rarely found l)eyond the immediate vicinity of the site (Fig. 20). On the surface, as well as in the stratum l^etween the false ^i^Smim. '*. .V' * Fig. 20. — Diphtheei.\l Membrane (Pure). Bacilli la sitv. membrane and the denuded epithelium, the streptococcus ])Vogenes and staphylococcus aureus and allius are also very frequent com- panions of the l>acillus (Fig. 21); these organisms, unlike the liacilli, travel much further into tlie deeper tissues, as well as to the lymphatics and lilood vessels, when they constitute tlie cause of secondary infecti^'e processes in the lymphatic glands, lungs, spleen, &c. The lower strata of the mucous memlirane are also invaded by the exudation, and tlie coagulation process extends PATHOLOGY. 71 deeply into the sub-mucous layers, which become infiltrated with small inflammatory cells, leucocytes, and micrococci. By this process the membrane becomes progressively firmer and tougher by each fresh deposit from beneath. Thus, the external or upper layer of the diphtherial false membrane which is oldest, when it becomes disintegrated, is thrown off in the form of a slough. The subjacent epithelium soon disappears, and on the denuded surface a layer consisting of small cells, pus cells, and granular dihris is formed, separating it from the dead material above. - ,.^-- ■ « \: f ■..»>.'■ * .. •* • "% ,.' .mtii'^-':- ^' , '.\ '" „'■* > •^■, '^■•' J" « " '<'.''. ': ■^:. ''^" • V^>; ■1^- '-■ ■■ ., » .,■ »■■■ ■ • • • 1 ♦ * ■■ \ *' '■- **-";- " ■ » -> '?t: V * -^^ ^•ftfe* Tig. 21. — Diphtherial Membrane (Complex). Bacilli and Cocci in situ. The destructive process, extending deeper to the sub-mucous tissues, involves the blood vessels and the lymphatic channels. The blood vessels become constricted from pressure, local thrombosis and embolism follow, with ulceration, necrosis, gan- grene, and extravasation of blood. The lymphatics of the part are filled' with leucocytes, pus cells, and cocci, which, passing into the nearest lymphatic glands, produce swelling from infiltration of inflammatory cells, and finally suppuration. The diphtherial exudate is adherent, and can only be removed ■jz DIPHTHERIA. by the employment of some force, when a raw, inflamed, and bleeding surface is exposed. The membrane varies much in its colour, from that of white, faintly tinted with a pearly grey or lemon, to deep greyish green, brown, or almost black, the intensity of hue depending partly on the age of the exudate, and largely on the amount of blood extravasated. The diagnostic characteristic of a true diphtherial exudate is, that it contains the Klebs-LoeiHer bacillus, the presence of this organism being an irrefragable indication of the nature of the disease. When the malady marches towards cure, the bacilli diminish in number, and very often disappear with the membrane. On the other hand, they may persist long after the individual is apparently cured. Pseudo-diphtherial membrane is characterised by an excessive production of fibrinous material, which forms a network of delicate strands and fibres, enclosing in its meshes leucocytes, granular d&bris, and pus cells. The false membrane is attached by thia fibrinous threads to the surface of the tissues beneath. The exudate is largely soluble in dilute acetic acid. The epithelial cells become altered in character, swollen, and undergo fatty degeneration ; they desquamate freely. The membrane being only loosely adherent, can be easily stripped off, revealing a hypersemic, but not a bleeding base. The necrotic process does not involve the entire epithehal surface, for on removal of the exudate, some patches will be found to be normal in character and unaffected. As extravasations of blood into the interstices of the membrane are exceptional, pseudo-diphtherial exudation rarely presents a brown or black colour, but is usually of a whitish yellow, or greyish appearance. Lastly, although streptococci, staphylococci, and other micro- organisms may be, and often are present, the bacillus diphtherise is conspicuously absent, this last circumstance being the criterion of differentiation. CHAPTEE VI. BACTEKIOLOGICAL DIAGNOSIS OF DIPHTHERIA AND ITS ASSOCIATES. With the advance of bacteriology as a science, it has been repeatedly stated that it is impossible to make any exact diagnosis as to the diphtherial or non- diphtherial character of a membranous sore throat by clinical evidence alone. Although in our belief that dictum has emanated for the most part from bacteriologists of but limited clinical experience, we have already recognised that the facts ascertained by a bacterio- logical examination are capable of exercising a marked control on a bed-side diagnosis in the way of confirmation or correction. On this account we give this aspect of the question the precedence. The bacteriological diagnosis of diphtheria may be classified as follows : — (1) By a rough and ready method, the presence or absence of the diphtheria bacillus may be decided within a few minutes of first seeing the patient, or at least immediately on the return of the physician to his consulting room. Eoux and Yersin consider this method conclusive whenever the results are positive. (2) A provisionally negative diagnosis may be made by the absence of the characteristic colonies of the bacillus in a culture tube, after an incubation of 24 hours at a temperature of 37° C. (3) A provisionally positive diagnosis may be given by the naked eye appearances of a colony of the diphtheria bacillus similarly obtained. (4) A provisional diagnosis, positive or negative, of those micro-organisms, which are the more or less frequent associates 74 DIPHTHERIA. of diphtheria, may be determined by the presence or absence of their colonies, after incubation of a culture on blood serum for more than 24 hours. (5) These provisional diagnoses can be rendered certain by the microscope. (6) By the process of sub-culture the bacilli may be obtained pure, and the degree of their virulence may be estimated by experimental injections into lower animals. It is of first importance, in making an examination of throat secretions or exudations, that, whatever the method pursued, no local antiseptics should have been employed for some hours pre- viously. Neglect of this precaution may render the diagnosis entirely futile. Method 1. A portion of the membrane or suspicious exudate — preferably from the site where the membrane is oldest — is removed by means of a piece of absorbent cotton wool, twisted round the end of a piece of thick wire, or held by a pair of forceps. The cotton wool swab is then wrapped in oilsilk — previously passed through boiling water — or placed in a sterilised test-tube, and in this is either carried home, or sent to a laboratory. The next step is to pick up by dissecting forceps a small portion of the membrane thus obtained, and to dry it by means of blotting- paper. Still held by the forceps it is then rubbed over the surface of a clean cover-glass. The film is then allowed to dry, and the cover-glass is passed lightly through the flame of a spirit lamp three or four times to fix the film to the glass. The film is next stained with Loeffler's blue, gentian violet, or by Eoux's mixture of dahlia violet and methyl-green. [For details of preparation see Formulae, Chapter XIII.] By using this combined stain of Eoux, the specific bacilli of diphtheria are coloured much more rapidly and intensely than the other accompanying buccal microbes. BACTERIOLOGICAL DIAGNOSIS. 75 The method of staining the film is as follows : — Two or three drops of the staining fluid are dropped on the prepared cover-glass, and allowed to remain in contact with the displayed exudate for a few minutes. The excess of the stain is then washed away with a gentle stream of water, the glass lightly dried with blotting- paper, and mounted for examination under the microscope. An immersion lens should be used. The bacilli of diphtheria, if present, should be at once recognised by the typical characters which have already been so minutely described and illustrated ; but the following may be here recalled as among the most noteworthy and constant characteristics : — The gathering together of the bacilh into small clumps or groups, often of three and four, lying parallel to one another, but seldom end to end. The arrangement by which two of the bacilli form an obtuse angle, and recall the form of an open letter, v, or of a circumflex accent; while other groups resemble the letters, n, m, w, Y, and X ; also T and l- These points of identification are almost more useful for this quick method of diagnosis, than the actual shape or size of the rods themselves ; though these as well as the clubbed ends and the segmental staining, will further help to a diagnosis of greater accuracy. In the majority of cases, the bacilli are so numerous that the nature of the case is at once evident ; but in others, where they are more scattered, the manner in which they group themselves is so distinctive, as to almost ensure against a mistake, even by a tyro. Louis Martin has well likened this grouping of the bacilli, to the manner in which a number of small pins arrange themselves if allowed to drop in little heaps on a table. By this simple method not only may the bacilli be detected but, to some extent, their association with other organisms of prognostic importance may be determined. All these must be noted. Are they streptococci, staphylococci, or diplococci, including the variety called the Brisou coccus, or are they ordinary mouth microbes, some of these which much resemble 76 DIPHTHERIA. the diphtheria bacillus, and are mainly to be distinguished by the much deeper stain taken on by the latter, and by the differences of group arrangement? If no diphtheria bacilli are found, then it should be noted what other microbes are present. If streptococci, what is their arrangement, Rigid, Flexuous, or Batcdlion ? These cocci may give trouble when they are numerous, and the diphtheria bacilli are few ; but at least they indicate that antiseptic precau- tions should be observed with more than usual vigilance. An objection that has been raised against the cover-glass method is, that since the mouth microbes are to some extent revealed, the average eye is apt to be confused by the multiplicity of organisms. However, this can be avoided by using Gram's selective method of staining, which, only revealing the bacilli, cocci, and pneumo- cocci, does not affect the buccal microbes, which are therefore invisible. Here, then, is another valuable point in diagnosis. Another objection to this rapid process is, that while in many cases the presence of the bacillus is satisfactorily demonstrated, a negative result may be obtained, due to the fact that there happened to be no bacilli on the cover-glass preparation, and especially may this occur when there is little or no membrane, and the swab only brings away secretion and mucus. Where this doubt exists, a diagnosis cannot be conclusive until one of the more exact methods has been adopted. But should the typical diphtheria bacillus have been recognised by the aid of the microscope, we need go no further. The whole process has not occupied many minutes. Method 2. Presuming that bacilli have not been found on microscopic examination, or that we are desirous of a more complete diagnosis, we proceed to make a streak culture. The best medium hitherto employed is the solidified blood serum, which can be obtained sterilised in tubes, ready for use, BACTERIOLOGICAL DIAGNOSIS. 77 from the Clinical Eesearch Association, from the Institute of Preventive Medicine, or from any bacteriological laboratory. Although the methods of carrying out these procedures will be briefly outlined here, those who have not had the opportunity of making, themselves acquainted with this science, or who have not leisure to pursue it, will probably prefer to have the' examination made by an expert, it being always remembered that the actual sowing of the seed must be done by themselves at the bedside. The culture may be of two kinds, either by the swab or by the needle. The apparatus for employment of the swab culture is supplied on application from any of the sources already enumerated. It consists of two sterilised glass tubes, one containing the swal >, the other the culture medium. The swab is taken out of the glass tube in which it is sent, and the patient's tongue being depressed, the cotton brush is rubbed freely over the mucous membrane of the pharynx and tonsils, and especially against any visible membrane, that oldest being pre- ferably selected ; without laying the swab down, the rubber cap and wool plug are removed from the culture tube and retained between the fingers, so as to prevent contamination. The swab should then be inserted, and that portion of it which has touched the membrane, or the pharyngeal or tonsillar surfaces, should be lightly but thoroughly rubbed all over the surface of the culture medium, taking care not to break it. The swab should then be replaced in its own tube, and both the tubes should be carefully replugged and covered. The needle or streak culture is made by picking up a minute portion of the false membrane or exudation by a special spatula- pointed platinum needle, and having removed the cap or cotton wool plug from the culture tube, two or three lines are drawn, parallel and close together, with just sufficient firmness to mark but not to disturb the surface of the serum; then, without recharging the needle, similar cultures should be made on one or two other culture tubes. 78 DIPHTHERIA. In from fourteen to eighteen hours— if the case be one of true diphtheria — the colonies of the bacillus first become apparent and characteristic; and, in the opinion of Eoux, if there be no such appearance within twenty-four hours, a negative diagnosis may be formed, — at least as to that particular culture. But here again we are not justified in saying that the membrane under examination has not been formed by the diphtheria bacillus, until repeated cultures have been made from it. Method 3. Presuming that our colonies have developed, how are we to know that they are those of the diphtheria bacillus ? After the culture tubes have been in the incubator at a temper- ature of 35° to 37° C. for fourteen to eighteen hours, colonies of the diphtheria bacillus appear, as whitish-grey specks, each about the size of, a pin's head ; the contour is regular and the surface dry. By transmitted light the centre of the colony is seen to be thicker and more opaque than the periphery, which is translucent. An almost positive diagnosis of the presence of the diphtheria bacillus is therefore established, that is to say, a positive naked- eye diagnosis has been obtained. Method 4. After twenty-four hours other microbes form colonies, and may complicate the diagnosis ; for example, the colonies formed by the Brisou coccus bear a certain resemblance to those of the bacillus diphtherise; but they are smaller, the svirface is moist, and their periphery is more opaque than the centre. The microscope, of course, is the sine, qua non of accurate distinction between them, and should always be employed to control the diagnosis. The Brisou cocci appear as diplococci and cocci in rosettes, threes, fours, &c. (Fig. 10). The streptococcus is of much slower growth, and its colonies BACTERIOLOGICAL DIAGNOSIS. 79 may be distinguished from those of the bacillus by the fact that they do not begin to form until the lapse of at least twenty- four hours. They appear as white colonies, very much smaller than those of the bacillus, resembling, as compared to the pin heads of colonies of the latter, so many pin points. The staphylococcus resembles the sbreptococcus in its slow rate of growth; its colonies are much larger than those of the bacillus diphtherise. They are of a flocculent or snow-white appearance, darker in the centre, but thinner at the edges, and the halo-like effect at their periphery is somewhat increased over what is observed in a colony of the Klebs-Loeffler organism. These colonies often take from two to three days to develop properly. A yellowish or golden tint may appear in some cases, but it is by no means either an early or a constant occurrence. A preference has been expressed for blood serum as a culture medium, because on it the diphtheria bacilli seem to grow more rapidly, and to preserve more of their special characteristics than they do when developed on agar-agar, glycerine-agar, gelatine, &c. Dr. Hayward has advocated solidified hydrocele fluid, long known as a culture medium, as of especial value for cultivation of the diphtheria bacillus, and Dr. Powell White has greatly simphfied and accelerated the process by which this medium can be prepared. The advantages which these two workers claim for the hydrocele medium are : — (1) It is easy to obtain and prepare. (2) It is perfectly transparent, and forms a firm, clear, and solid nutrient medium. (3) It is especially suited for the separation of the diphtheria bacillus, which grows readily upon it, and in the same forms as on the blood serum. Dr. White has " obtained a distinct growth after only seven hours' incubation." (4) It is inimical to the growth of many of the associated organisms of diphtheria. 8o DIPHTHERIA. Streptococci grow on hydrocele fluid much more slowly than the diphtheria bacillus, not being observed for three or four days, while staphylococcus aureus grows so very slowly, and with less disposition to produce the yellow coloration, as almost to put it out of court. It follows, therefore, from the foregoing observations, that it may be of advantage, when making cultures from suspected cases of diphtheria, to control the culture made on blood serum by another culture made at the same time on hydrocele fluid. Method 5. In making a microscopic examination of a colony, it is well that it should be done at an early stage, before the medium has been invaded by the growth of associated organisms; in other words, almost so soon as any growth is evident on the culture-medium. Details of the procedure are superfluous, and the various microscopic appearances have already been detailed. Method 6. Sub-cultures are made from the original cultivation, in a manner precisely to that already described in Method 2. These are especially valuable when it is desirable to eliminate the bacillus from colonies of other micro-organisms with which it may be associated, and also when the microscopical appearances of the first culture suggest that the bacillus has become attenuated or non- virulent. After making a sub-culture from such a growth, and proceeding to test the resultant diluted with bouillon by injection of a rabbit or guinea-pig, it is said that these attenuated bacilli are invariably innocuous ; but we have no personal experience of this experiment. We have now described — we trust with sufficient detail — the life history of the specific organism of diphtheria, and of the organisms of significance with which it may be associated, as well BACTERIOLOGICAL DIAGNOSIS.^ 8i as the methods by which a bacteriological diagnosis may be made. The following table includes twelve varieties of membranous sore throat, the nature of which can be bacteriologically deter- mmed. It comprises most of those of pure diphtheria, complex diphtheria, and such as may occasionally and reasonably be mis- taken for diphtheria. The classification is based rather on the preponderance of the particular organism present, than as actually containing only those that are named in each class. Class I. Diphtheria (simplex). II. Diphtheria bacillus with streptococcus. III. Diphtheria bacillus with strepto- and staphylococcus. IV. Diphtheria with strepto- and diplococcus. V. Diphtheria bacillus with diplococcus. VI. Streptococcus. VII. Strepto- and diplococcus. VIII. Staphylococcus. IX. Staphylo- and diplococcus. X. Diplococcus. XI. Diplococcus and a. mycelium. XII. Indeterminate. Without anticipating the histories of our cases in detail this chapter may be fitly concluded by a brief preliminary record of those specially selected to illustrate various points of interest ; and in this conjunction by comparison of the bacteriological features with the bedside diagnosis. This table very satisfactorily demonstrates the general agree- ment of a bedside diagnosis with that obtained by a bacteriological examination, it being understood that in each case the latter was made independently and entirely without knowledge of any clinical details. In one instance (No. 12), a bacteriological examination of the secretion taken from the fauces failed to detect the presence of the specific bacillus of diphtheria ; nevertheless, a culture made 82 DIPHTHERIA. P^ eg 15 o £ « S 60 CD fl ^ '^■S is- Ph'-*3 "lis g S,C 0)^ sd 2 " Q .- g -a „ a, -g ■S.S ja V c3 „ '^ ¥ ^ a a c3 ^ bD § u ii .& ti ft a ra 3 *S *B S .-S « 2 2 •o^'g.S'ft t3 bO 3 il ■^ I Ti ;> p ^ P 1^ X a H !'< >< BACTERIOLOGICAL DIAGNOSIS. 83 from an aural discharge, which occurred 14 days after admission, demonstrated the presence of the diphtheria bacillus in association with pyogenic cocci. We have knowledge of two other analogous cases, each of which were followed by typical paralysis. On the other hand, the diphtheria bacillus was found of the long variety, that is, of the kind which is beginning to be recognised as indicating a virulent form of the disease, in a case (No. 4) clinically diagnosed as non-diphtherial : no paralytic sequelee followed, and non-virulent bacilli were found on the faucial wound two days after tonsillotomy three and a half months later. One more illustrative example is aiforded in Case 20 : the patient was certified into hospital by an experienced practitioner as one of probable diphtheria. On clinical evidences we had no doubts as to its being pseudo-diphtherial, but the bacteriological reports were not quite unanimous. Two repeated examinations of separate cultures failed to detect bacilli. Another independent examination revealed a very few short, stunted bacilli (Fig. 51). The patient made a rapid recovery, without sequelas. It is true that a suggestion has been made that paralytic sequelse may possibly occur in throats that are coccal and not bacillary, the opinion being held that paralysis is not necessarily proof positive that the case has been one of true diphtheria. In the present state of our knowledge it is impossible to substantiate such a position. In any case, the occurrence would be most exceptional, and could only be entertained after a rigid pro- cess of exclusion. It has, however, been pointed out by Sims Woodhead, Thresh, and others, that the negative evidence of diphtheria is sometimes contradicted by positive clinical symptoms exhibited by the patient during the course of the malady. These circumstances are mentioned to demonstrate that the bacterio- logical diagnosis is not always so infallible as has been advanced in some quarters, but we would not for a moment claim that these exceptional discrepancies are of sufficient frequency to cast any general discredit on the direct testimony to be gained from the laboratory. CHAPTER VII. THE CLINICAL DIAGNOSIS OF DIPHTHEEIA AND ITS ASSOCIATES. Hating occupied ourselves in the preceding chapter with a consideration of those points of diagnosis which can be solved by bacteriology, we now turn to those elements of diagnosis which should be familiar to, and adopted by, every well-informed practitioner on his first interview with any patient supposed to be suffering from diphtheria. It is a common experience of everyone connected with hospitals where diphtheria is treated as an infectious disease, and with those consulted in such cases, for their aid and opinion to be sought by persons who are supposed to be the victims of diphtheria, but who, on quite cursory inspection, are recognised as suffering from some more simple malady. Such mistakes require to be very charitably considered, for obvious as they now and then may appear to the expert who sees the case for the first time late in its history, there is probably no throat affection more protean in its clinical disguises, and more deceptive in its initial stages than is diphtheria. Of a quite separate category are those inflammations of the throat accompanied by exudation of pseudo-membrane, which occur during the course of the specific fevers. Until the eluci- dation afforded by bacteriology, these have been considered by the majority of authors from the time of Home in 1765, to be truly diphtheric, notwithstanding many vigorous and weighty argu- ments to the contrary. We now know, as has been mentioned more than once already, and as we may have occasion to repeat CLINICAL DIAGNOSIS. 85 more than once again, that the membranous inflammations of the throat exhibited previously to, or during the early stages of any of the exanthemata, are not, as a rule, of the nature of true diphtheria ; while such as are implanted on them in defervescence or as sequelae, are almost invariably proved to be absolutely of that nature by the presence of the Klebs-Loeffler bacillus. As a direct result of bacteriological enthusiasm there is a general confession, on the part of recent authors, that the clinical evidences of these diseases, at least so far as they are afforded in the throat, are so difficult or even impossible of distinction, as only to be settled by a culture and a microscopical examination. .To such a vrholesale surrender of our clinical fortress we cannot for a moment submit ; though it must be frankly conceded that, not rarely, cases occur in which the most experienced clinical observer may find himself at fault. To render these occasions less frequent an attempt will be made to demonstrate that these doubts can be solved, in a large degree, by a careful comparison of the symptoms, both physical and functional, of those membranous sore throats which are charac- terised by the micro-organism recognised as specific of diph- theria, either alone or in association with cocci; and by due recognition of other more special evidences of the different diseases in which they are found. If the clinician would work with the bacteriologist on these lines it ought not to be long before the occasions on which an error in diagnosis on the part of the former has to be corrected by the researches of the latter, will become so rare as to be exceptional. On the other hand, it is with deference suggested that it would be well if the bacteriologist would make it a more general practice to visit the wards, and be thus enabled to compare the conclusions formed in the laboratory with the data afforded at the bedside of the patient. The following are the special points on which information should be obtained before proceeding to an examination of any case suspected to be diphtheria : — 86 DIPHTHERIA. The age of the patient. The number of members in the family. The pre-existence of similar throat affections among its members. Evidence of exposure to infection by personal communication, or otherwise. History of recent attacks of diphtheria in the household, or of any of the diseases in which sore throat is a symptom, or which are recognised as predisponents to diphtheria. Finally, the condition of the sanitary surroundings of the patient. Next, inquiry should be carefully made as to the exact date of the initial symptoms, in order to determine the probable period of incubation. The experimental incubation period, when com- municated by inoculation in the lower animals, is short, and varies from twelve hours to three days. It is said to be about the same period when a human patient is infected by direct contact, and our own experience leads us to concur that the disease is not infrequently developed at the minimum interval. Leslie Phillips reports a very interesting case in which some of the same instruments were used on the same day, first in the operation for tracheotomy for diphtheria, and secondly for circum- cision ; the circumcised child had pseudo-membrane on the prepuce on the fourth day. In ordinary circumstances, the period between the exposure to the contagion and the appearance of false membrane in the throat is probably from one to four days. A longer interval is exceptional. Evidence as to the mode of onset, whether sudden or gradual, is of great importance; the former being the rule in diphtheria, especially among infants and very young children. In those over 10 years of age and in adults the development may be slower. Having satisfied ourselves on these points, we shall How, by a brief description of the symptoms, proceed to indicate the diagnostic value of each. CLINICAL DIAGNOSIS. 87 The prodromata are : general malaise, quickly followed by headache, nausea, pain in the hack and limbs, concurrently with the early throat symptoms. The invasion is rarely marked by rigors in children, as mentioned by Schech, for such a circumstance is as unusual in this as in any other disease of childhood. Vomiting is only an occasional, and by -no means so constant, a forerunner of diphtheria as of scarlet fever. Diarrhcea is, some- times, present, but the opposite also obtains. The neck is some- times complained of as feeling stiff, with pain at the angle of the jaw, but neither within the throat itself, on opening the mouth, nor in swallowing, is there either appreciable pain or difficulty experienced, thus differentiating the malady from ordinary forms of tonsillitis ; and, indeed, this absence of pain is of valuable diagnostic significance. Within a few hours of these first symptoms, or — exceptionally — after a longer time, the special local manifestations in the pharynx become obvious ; the throat feels dry, and there is a desire to hawk and clear the fauces. The voice is often distinctly hoarse and rough, even before there is membrane in the larynx, and should this have spread to that situation before the patient is seen, vocal tone may have been altogether lost. With this, there will be observed also a laryngeal cough, noisy stridor, and dyspncea, due to obstruc- tion, with exacerbations of true spasm. The tonsils and fauces are, as a rule, first attacked, being generally red, swollen, and thickened ; they soon become the seat of patches of exudation, which can be observed to increase in thick- ness, to become tougher in consistence, and to extend, sometimes rapidly, in area. Detailed description of the exudation is for sake of convenience deferred. There is very little which is distinctive in the appearance of the tongue, but one should note the absence of the thickly furred and foul surface, seen in ordinary tonsillitis ; and bear in mind the equally distinctive appearances of this organ in scarlet fever. Young children, who are the subjects of diphtheria, present at a very early period in the attack a particularly characteristic pallor 88 DIPHTHERIA. and waxiness of the complexion, with a pinching of the nostrils. Sometimes they are fretful, but even in the early stages are far more often listless and lethargic, and they seldom give any indication, either by their temper or actions, of acute pain ; all these symptoms being indicative of the asthenic character of the disease. An erythematous eruption on the trunk, and " blanket " rash is, although not common, sometimes to be noted in diphtheria ; albeit, it is particularly evanescent, such a rash may obscure or confuse an exact diagnosis. The nostrils being not infrequently implicated, their normal functions are interfered with, and fluids may escape through the nose during swallowing, even before the palatal muscles have become paretic. Nasal discharge, when present, is usually of a peculiarly foetid, sanious, and irritating character ; and is of diag- nostic import. It is, therefore, important to examine the nares for membrane, for which purpose, if the lumen be obstructed by mucus, a warm alkaline douche may be first employed. Epistaxis, always a grave symptom, is by no means uncommon. When the posterior surface of the uvula is the site of exudation, the posterior nasal space is almost always involved. Exudation rarely commences in the anterior nares. The temperature in cases of diphtheria is usually low in com- parison with the acuteness of the constitutional disturbances characteristic of the disease. From our table of 1000 cases which came under observation, on an average, on the third day of the diphtherial attack, the temperature in 80 per cent, was 101° F., while in 50 per cent, the average temperature during its course was below 99° F. Acute adenitis, as a complication in the course of an attack of diphtheria, is attended by a rise of temperature, sometimes to the extent of 104° to 106°, but the hyperpyrexia quickly subsides, except in those cases where suppuration ensues, and then on liberation of the pus. When diphtheria is com- plicated with any of the exanthemata, the temperature chart CLINICAL DIAGNOSIS. 89 frequently partakes of the particular characteristics of the associated disease. But independently of these circumstances, the thermometer gives indications of the first importance in diphtheria, and, indeed, there are few diseases in which it affords greater aid, albeit the variations are but rarely extreme. As a rule, an increase may be taken to point to a further extension of membrane or a compHca- tion ; reduction within certain limits is a sign of improvement. Commencing with a more or less rapid rise, rarely exceeding 102° F., the temperature is immediately lowered on the appear- ance of false membrane, and falls to normal, or- a point or two below it — a fact which is readily accounted for by the asthenic character of the malady. A further rise may give warning of an Adenitis, which we have already considered, of Nephritis, Otitis, or of Broncho-pneumonia; it may also indicate the occurrence of Parcdysis, or may be premonitory of Cardiac implication, when we may soon witness a sudden and serious fall below the normal. This subsidence is to be taken as an almost unfailing premonition of death by Asthenia. The distinguishing feature in the pulse of diphtheria is its extreme rapidity in proportion to the temperature ; this is much more marked than in scarlatina, in which the temperature is distinctly high, and for a longer period. Both the rate, force, and regularity are influenced by the profound asthenia which charac- terises the constitutional toxaemia, and an abnormally slow pulse indicates complications, the gravity of which will be considered under the elements of prognosis. Adenitis. — The character and situation of inflammatory enlargements of the lymphatic glands next claim our attention as being of almost constant occurrence in pharyngeal diphtheria, and of considerable diagnostic importance. There is a distinct difference in the portion of the glandular region affected. In true simple diphtheria, the cervical glands are those mostly attacked. This may be in the form of enlargement and 90 DIPHTHERIA. tenderness of the whole chain of glands, which can be separately felt ; or, in the gravest cases, as one large swollen mass in the neck, in which the parotid may also be involved. In complex diphtheria, both the cervical and sub-maxil- lary glands are affected ; and in pseudo-diphtheria — that of scarlet fever, for example — the sub-maxillary glands are those most frequently affected. In diphtheria, following scarlet or other specific fever, or in any circumstances in which streptococci are associated with the diphtheria bacillus, both sets of glands are liable to be inflamed concurrently {Case, 5). Adenitis is far more common in scarlet fever than in diphtheria ; indeed, it may be taken as one of the ordinary symptoms of the former disease. It is far more intense, and suppuration, to which it is also more prone, takes place at a much earlier date. Never- theless, suppurating adenitis and cellulitis are far more frequent in true diphtheria, especially in the cocco-bacillary varieties, than is generally thought ; for this complication, or— as it may almost be termed — this sequela, was found in 9'75 per cent, of our 1000 cases. Albuminuria. — The quantity of urine excreted, and its specific gravity, are to be noted night and morning, with efficient tests according to indications. The presence of albumen in the urine is not of great diagnostic importance in diphtheria. True, it is present in about one-third of all cases, but it is likewise to be found in many other varieties of inflammation of the throat of non- diphtherial nature. The prognostic significance of albuminuria may be deferred. The urine in diphtheria contains an eax&ss of urea, and, in the majority of cases, epithelial cells and casts ; but hcematuria is rare by comparison with its frequency in scarlet fever. Kenal complications are an early manifestation in diphtheria, as compared with those of scarlet fever. There are, however, exceptions to this sequence in both directions. Some perversion of function of the special senses of smell, taste, and hearing will often be found if carefully looked for. The odour of the Ireath is not always tainted, but in malignant CLINICAL DIAGNOSIS. 91 cases is so extremely offensive that no caution is necessary in regard to the danger of inhaling it. It is important that the practitioner should satisfy himself on all the foregoing data before he proceeds to examine the throat minutely. This is our next step. We have already noted that the fauces are more or less inflamed ui patients attacked with diphtheria, though the hypereemia in the case of this disease is always of a lower grade than in that of a throat manifestation in connection with scarlet fever or measles. It is quite exceptional for diphtheria to exist without more or less exudation in some portion of the air passages ; and we shall there- fore, in further investigation of this region, assume that membrane is present in the cases under our observation for the purpose of diagnosis. And first as to the site of the membrane. Valuable information on this point may be gained by an analysis of 1000 consecutive cases of diphtheria, to which we have already taken occasion to allude for statistical purposes on other points of clinical interest. Table 0/ 1000 cases of diphtheria, showing the relative frequency of sites of the membrane. Part Affected. No. Fauces (alone), . . 672 Larynx „ -4 NostrUs „ . . 2 Fauces and Larynx, . 109 Fauces and Nostrils, . 165 Fauces, Larynx, and Nostrils, . 46 Labial or Buccal only, . 1 Hard Palate only, . 1 1000 Note. — There were six cases in the series in which the membrane extended into the buccal cavity and forward to the hard palate. The above table speaks' for itself, but there are a few points that merit expansion. 92 DIPHTHERIA. As to the tonsils, these were the sites in all the cases where the situation is described as that of the fauces, and this disposition to attack the tonsillar tissue is evidenced not only in the faucial region, but in the pharyngeal vault, where is situated the pharyngeal tonsil, at the orifice of the Eustachian tubes (tubal tonsil), at the base of the tongue (lingual tonsil), and, finally, in the ventricles of the larynx, the glandular tissue of which may be held to represent the laryngeal tonsil. It is a peculiarity of the diphtheric exudation to start on some little prominence, such as the uvula, the free edge of the epiglottis, on the eminences of the cartilages of Wrisberg and Santorini, or in some small recess, such as those of the lacunae of the tonsils, and of the ventricles. As to the larynx, the figures in the table may be taken as rather underestimating the frequency of laryngeal extension, for in this series the laryngoscope was not employed. But admitting that a laryngoscopic examination is attended by considerable difficulties in all young children, and especially in the subjects of diphtheria, in at least 90 per cent, of whom enlargement of the tonsils proves an obstacle to a complete view of the larynx, those in which the epiglottis could not be seen must constitute a very small minority. And it is to be regretted that, at so mature a period of the art of lai-yngoscopy, the mirror is still so rarely employed in the diagnosis of diphtheria except by specialists. For not only would diagnosis be thereby rendered more complete, but in the matter of treatment, intra-laryngeal applications, and especially intubation — as we insisted on its first re-introduction — would be more easy of accomplishment, and attended by more satisfactory results, if the hand of the operator were habitually guided by the reflection of the larynx in the mirror. The membrane in pure and in complex diphtheria. — The diphtherial membrane in a typical case, — although described by so careful an observer as the late Sir Morell Mackenzie, as commencing with an infiltration at certain points, of a yellow substance — in our CLINICAL DIAGNOSIS. 93 own experience, begins almost invariably as a thin bluish-white deposit, something like a shaving from the boiled white of an egg of the duck, goose, or plover. • As the deposit increases in thickness, it gradually becomes more white and opaque, resembling the boiled albumen of a fowl's egg, or it may then partake of a very pale lemon tint. Then it becomes of a yellowish or greenish grey, brown, and sometimes almost black, as the necrotic process advances, or as blood is extravasated. Only in the comparatively uncommon case of a lacunar diphtheria do we see the exudation commencing as discrete spots of deposit, which may be of yellow colour at the very first onset {Case 4), and, even when coalesced, may never exhibit the pearly or opalescent appearance which characterises the more ordinary form on its first manifestation. The membrane is sometimes "plastered," as if put on with a palette knife, or " laid on with a trowel." This is especially well seen in the illustration to Case 14, page 123. More commonly the deposit is of unequal thickness, occasionally leaving exposed areas of uncovered and inflamed mucous membrane {Oases 1 and 7). The edges are often thicker than the centre {Cases 7 and 14), and when about to separate, become crinkled and everted {Cases 7 and 8). Shreds or strips of the membrane can be more or less easily removed by forceps, with the result of an exposure of a raw bleeding surface {Case 2), or of bleeding points {Case 3), followed, if left untreated remedially, or even in spite of treat- ment, by a re-formation of the membranous deposit. A diagnostic feature of the exudation of true diphtheria is that the membrane is deposited not only on the tonsils, as in pseudo- diphtheric inflammations, but also on the pillars of the fauces, the uvula, and on the posterior surface of the uvula {Cases 2, 7, 8, and 10), this last situation being almost pathognomonic. This investment of the uvula with membrane is so complete that Trousseau's description of a cast of it when shed, as resembling the finger of a glove, will occur to every one as most apt. When the membrane is observed at the side or edge of the uvula, it is an almost certain indication that the whole posterior surface is in- 94 DIPHTHERIA. volved, and this can be proved by turning up the uvula with the end of a spatula. It may also spread to the soft palate {Case 2), and even to the hard palate ; we have, indeed, seen it lining almost the entire buccal cavity. Sometimes it invades the gums. The membrane extends backwards to the posterior wall of the pharynx, and into the post-nasal space; it may envelop the turbinals; rarely, it may commence in the anterior nares, and quite occasionally is limited to the nasal fosste (Frontispiece). From the pharyngeal vault the membrane may extend along the Eustachian tubes (Case 12). Diphtherial exudation has a far greater tendency to travel downwards into the larynx than is recognised by those unaccus- tomed to use the laryngeal mirror, though quite often it does not reach further than the epiglottis {Case 11). In these circum- stances, there may be little or no laryngeal distress, but, of course, in many other cases it seriously involves the glottis, and may extend the whole way down the trachea (Frontispiece), and even to several divisions of the bronchi. (Edema, by which is meant sub-mucous effusion giving translucency to tissues of the fauces or larynx is, according to our experience, almost unknown in pure diphtheria, in this respect strongly differentiating the disease from the false varieties, especially those characterised by the presence of the milder forms of cocci. Casts, more or less complete, are con- stantly shed from the tonsils, uvula, and from the air-passages, and, what is not so commonly known, from the nasal fossae {Case 8). When the nose is affected, the nasal discharge is either serous or sero-sanguineous ; epistaxis is common, and the peculiar f cetor of true diphtheria is, by accumulation of secretion in the nasal passages, more than usually emphasised (Cases 2 and 6). False membrane in true diphtheria is not all deposited at the same time, and patches of variations of ^exudation of different ages, and consequently of different consistence and colour, may often be witnessed at different sites in the same throat. This is well exemplified in the illustration to Case 1, and the circumstance is of assistance to a differential diagnosis. CLINICAL DIAGNOSIS. 95 It is difficult to say what, if any, are the definite clinical dis- tinctions to be drawn between the physical appearances of the membrane of pure diphtheria and that of the impure or complex forms ; but there is a decided increase of phlegmon and swelling of the mucosa in those eases in which the streptococcus is specially predominant. Particularly is this so if the organism chains itself in that arrangement indicating its most virulent form — namely, the Conglomerate or Batallion. "When these cocci so predominate, the membrane may not be by any means so abundant as in pure diphtheria, the streptococci seeming in some degree to swamp the bacillus. This feature was very marked in Cases 5 and 6. The membrane in pseudo-diphtheria. — We have already remarked that a membranous sore throat, characterised by the presence of the Klebs-Loeffler bacillus, in association with strepto- cocci, not infrequently represents a diphtheria supervening on one or other of the exanthemata, of which scarlet fever is the most common. In like manner, a sore throat, in which the streptococcus is the sole organism present, usually represents a pseudo-diphtheria of the same class of infectious fever; not, we repeat, that it is intended to affirm that the streptococcus is the specific microbe of scarlet fever, for that still remains to be discovered. In these cases, the chaining of the cocci is generally of the flexuous variety. Streptococci in short, rigid chains, when associated with either staphylococci or diplococci, are usually characteristic of sore throats of a septic or insanitary origin, and in many of these cases there is little or no membrane present. This last point is also to be observed in some instances in which staphylococci are the pre- dominant organisms, but as a rule there is an abundance of exudation of a much more yellow colour, than that in either the pure or complex diphtheria, or in that of the streptococcal mem- brane ; the exudate in these circumstances, moreover, is sometimes accompanied by much viscid secretion {Gases 19 and 20) ; it does not separate readily, and when removed but a slightly hsemorrhagic 96 DIPHTHERIA. surface is exposed. In this variety of sore throat suppuration of the tonsils is of common occurrence. Finally, with regard to the diplococcus, we have already seen that cocci arranged in pairs are not responsible for any serious form of membranous sore throat; its presence, when associated with the bacillus of diphtheria, and with other cocci of graver significance than itself, has appeared to us to retard the clearing of the throat from membrane, and to give it a somewhat " dirty " character. No more need be said on the characteristics of the exudate. We shall now proceed to describe the chief points in the differential diagnosis between diphtheria and the pseudo-diphtherise which occur during the course of various specific fevers, and some of the minor forms of inflammatory sore throat, all of which may for our present purpose be considered as of pseudo-diphtherial character. Scarlet Fever. — Inflammation of the fauces is the rule in all cases of scarlet fever, however mild their character. The throat appearances bear a strong resemblance to those of tonsillitis, and the faucial inflammation is attended by almost as much functional pain, though there is not the same characteristic locking of the jaw on attempt to open the mouth which is almost pathognomonic of quinsy. "We have already alluded to the differential circum- stances of invariable and early vomiting and high temperature in scarlet fever, to which we may add its more sudden onset. A distinction may be made in the characters of the skin eruption. In the rare cases of such a manifestation in diphtheria the rash is erythematous, of late occurrence, and mostly appears on the neck and chest; in scarlatina it is punctiform, an early symptom, and attacks the skin of the whole body. The circum- stance of desquamation constitutes another, though naturally a tardy, element of differentiation. It is comparatively exceptional for a scarlet fever throat to be attended with false membrane. We are not in a position to give figures in support of this assertion, but Sann^, who wrote CLINICAL DIAGNOSIS. 97 before the discovery of the bacillus, found membranous exudation in 95 cases of scarlet fever, out of a total number of 229, of all varieties of what he called "secondary diphtheria." The com- plication, whenever it occurs, is rightly interpreted as of great gravity. The exudation is yellowish in colour, and, so to speak, dirtier, or greyer; the surrounding mucous membrane representing a more intense and extended form of hyperaemia than in true diphtheria. It cannot he stripped off in connected shreds, being rather pulpy, or, even pultaceous ; it is as it were more " inlaid " {Case 16). The pseudo-membrane has a tendency, as Soerensen says, to melt down into a purulent mass, and to quickly leave deep and destruc- tive ulcers, producing characteristic perforations in the pillars of the fauces. It frequently produces suppurative inflammation of the middle ear by extension through the Eustachian tubes, this event being attended by great pain. N"o membrane is observed in the nose, but there is often a purulent discharge. Epistaxis is not common, but heemorrhages from the throat are more frequent in this form than in any other, on account of the deep ravages made in the tissues. In fact, this strong disposition to bleed constitutes a marked difficulty in making a satisfactory diagnosis of the exact condition of a throat in scarlatina. Mem- brane extends to the air passages but rarely, and when the larynx is attacked, the inflammation is usually of the nature of an acute cedema, the results of the ulceration, for primary oedema of the throat in relation to scarlet fever is almost as rare as in diphtheria. Membranous laryngitis occurring during scarlatina is probably of cocco-bacillary origin. Measles. — Although it may not be possible to detect very much difference in the grade of the inflammation of the fauces from that of scarlet fever, those who have had experience will readily recognise that there is almost as much distinction between the appearance of the mucous membrane of the fauces in the angina without exudation in cases of measles, and that of scarlet fever, as there is in the cutaneous eruption. 98 DIPHTHERIA. The preliminary symptom of measles — Coryza — is emphasised in those cases of pseudo-diphtheria, which occur in its course, and the disposition to pulmonary congestion and bronchitis is another distinctive feature. Most marked, however, of all is the great redness of the con- junctivae, and the occasional production of membrane in this situation; certainly, in a case of conjunctival diphtheria — which by the way is very rare — we should be led to look for measles as the primary disease. Faucial membrane during the course of measles is only observed quite exceptionally, though true diph- theria is more often a sequel of this exanthem than of scarlet fever, in which, as has been already noted, a pseudo-diphtheria may precede the rash. There is, also, less tendency to suppuration and ulceration of the throat ; and although middle ear complica- tions like those in scarlet fever are common — much more so than generally supposed — in measles, they usually commence as a sero- mucous inflammation, while in scarlet fever they are almost always suppurative. Implication of the larynx and trachea is more common in measles than in scarlet fever, and occurs as a late complication. Acute membranous laryngitis (croup) without visible faucial deposits is relatively much more common in measles than in true diphtheria. In fact, as is well known, inflammation of the whole respiratory tract, and also of the alveoli, is a recognised characteristic of Eubeola. Whooping-Oough. — Pseudo-diphtheria is sometimes found asso- ciated with pertussis, and the manifestations, both in the throat and larynx, are not dissimilar to those found in measles. Distinction will, therefore, be inade by the characteristic symptoms of the parent disease. Typhoid Fever. — A certain amount of pharyngeal and laryn- geal inflammation is not uncommon in enteric fever, and if looked for, a faucial exudation, easily to be distinguished from aphtha by its microscopic features, may be seen about the third week. Independently of the special commemorative signs, the charac- CLINICAL DIAGNOSIS. 99 teristic point about the throat is that the membrane does not become thicker, does not separate more easily than in scarlet fever, and that it is characterised by the presence of staphylococci rather than by that of streptococci; lastly, it is altogether of a milder nature. As Morell Mackenzie has said, "though it (exudation) frequently commences in the larynx, and is often confined to that part, the diminished supply of air causes little inconvenience, owing to the medulla having, to a great extent, lost its sensibility to impressions. The obstruction to respiration is also less marked, from the fact of the disease in most cases attacking adults." But while probably the pseudo-membrane exhibited at any stage of a typhoid attack is far less frequently truly diphtherial than it is in the case of scarlet fever or measles, diphtheria as a sequel has been occasionally recorded, and each one of these three specific fevers has often been noted as prevalent, prior to and concurrent with a diphtheria outbreak. An interesting case is reported by Dr. Gayton to the Layvcet, May 5th, 1894, in which true diphtherial croup supervened on enteric fever on the fourteenth day after admission for the latter. Tracheotomy was performed, and the patient, a boy of eight years, made a good recovery. Dr. Gayton, commenting on this case, remarks that "the incidence of diphtheria during the course of enteric fever must be extremely rare, Sir William Jenner, Murchison, and others, who have written on the subject, not mentioning its occurrence." Smallpox. — As regards smallpox, careful inquiries from those whose experience of this disease can be numbered by thousands of eases, assure me that membranous exudation of the throat is practically unknown ; but it has been observed, in association with a very low and malignant type of this disease, that, deep ulcera- tions and necrosis may occur, leading to oedema of the glottis. The same remark applies to Typhus fever. In fact, it is doubtful in any post-mortem, examination made in either of IPO DIPHTHERIA. these diseases whether the larynx or trachea is ever found in a perfectly healthy state. A mild form of membranous exudation may be seen sometimes in cases of Chickenpox, and although membrane is almost un- known in Rotheln and in Mumps, the congestion and hypersemia of the mucous membrane of the fauces and pharynx in these disorders render them more susceptible to the attacks of the diphtheria bacillus. The diagnosis is not difficult in view of the general characters of the diseases. A differential diagnosis is occasionally more difficult in cases of milder forms of throat inflammations than in the throat mani- festations of the acute specific fevers, in which there are so many other marks of distinction. Thus, pharyngeal patches of diph- therial membrane may quite excusably be confounded with aphtha or herpes, with simple membranous inflammation, whether idiopathic or traumatic, with exudative lacunar tonsillitis, with phlegmonous pharyngitis, and with syphilis, especially in the very early secondary stages of this last-named specific affection, when mucous patches often bear a strong resem- blance to those of diphtheria, and more particularly in those cases in which there is slight pyrexia and glandular tenderness. We have seen in one of our cases that a pseudo-membrane may occur in low and debilitated constitutional states, and in general marasmus, which, in the instance under remark, led to a notification of diphtheria, and the removal of the patient to an infectious fever hospital {Gase, 23). The crucial test is the presence of the diphtheria bacillus, but independently of this, the history and subsequent progress of the case under observation should assist to a quick clearing up of the diagnosis. As to tonsillitis, it may generally be said that it is dangerous in an inverse proportion to the severity of the symptoms ; of these special mention may be made of the suddenness of onset, the high temperature, and, above all, the pain. It is worthy of repetition that the great difficulty in opening the mouth and the extreme dysphagia, so characteristic of the milder malady, will materially CLINICAL DIAGNOSIS. loi contribute to a correct recognition of the nature of the case at an early stage; and long before suppuration has occurred all doubts should have been dissipated. Not so much can now- a-days be said as to the distinction between the cheesy blocking of lacunae in tonsillitis' and diphtherial membrane, for we now know that many cases, judged by this symptom in pre-bacterio- logical times as of the former class, are truly diphtherial. More characteristic is the fact that in tonsillitis the membrane, or rather exudate, is limited to the gland, the creamy and easily cleared secretion of which can be readily distinguished from the firmly attached fibrinous membrane of diphtheria. Finally, quinsy is accompanied by much muco-salivary secretion of a viscid and clogging character ; diphtheria is a much drier disease. With aphtha and herpes, diphtheria will rarely be confounded even by the tyro after the second visit. As to membranous sore throat, apart from membranous laryn- gitis, we do not recognise such a disease uncomplicated by specific influences of constitution or hygiene. In pharyngeal erysipelas, which includes the septic sore throat of some authors, the tem- perature is higher ; there is always great distress ; the tissues are very (Edematous and livid; the cutaneous surface of the neck is usually involved, and membrane is rarely present, — at any rate of a consistence Hkely to lead to a more than momentary doubt. CHAPTER VIII. EECOED OF ILLUSTEATIVE CASES OF DIPHTHEEIA AND ITS ASSOCIATES. The various methods known to the bacteriologist, by which the specific organism iu a case of diphtheria or pseudo-diphtheria can be detected, as well as the more important elements of diagnosis at the bedside, having been now described and discussed, it appears convenient to here insert a record of cases illustrative of most of the points of interest, whether of parallelism or of apparent dis- crepancy front this two-fold aspect. It is true that, to avoid repetition, the elements of prognosis and some questions of treatment are in a measure anticipated by this order of arrangement ; but this, it is hoped, will be a minor inconvenience to the reader, and will be outweighed by the advantage of having a clear view of the lines on which our forecast and the indications for treatment should be laid. CLASS I. Bacillus UiPHTHERiiE. Case 1. Faucial exudation ; serum treatment ; anuria ; death. A female child, aged 8 years, admitted to hospital on November 17th, 1894, on the third day of the disease. Previous History. —The little patient, quite well on the morning of November 14th, and in her usual health at mid -day, returned from school in the evening complaining of headache, and of nausea even to the extent of actually vomiting. The child had lived with her parents in the same house for upwards of two and a RECORD OF ILLUSTRATIVE CASES. 103 half years, during which time tAvo .sisters ha.d died fr.jiii bronchitis. A school companion and near neighljour, in close intimacy, had been removed to the hospital on account of diphtlieria on the previous day. On admission, the fauces .m the left side were seen to l)e much swollen, with a pearly white exudation on tlie corresponding tonsil, which extended somewhat on to tlie soft palate. There wa,s also thin pellicular secretion on the right side, indicatmtr a more recent exudation at that site (Fio-. 22). The neck was 4 -/ ^^? xS-v ''( Fig. -l-l Fig. 2.5. swollen more on the left than on the right side. The temperature was 100" F. The bacteriological examination demonstrated a t}'pical growth of the bacillus diphtheria', almost without any otlier nuero- organism (Fig. 23). On the 18th the temperature was 100" F. The amount of urine passed was 12 ounces, and contained no edhumen. The patient slept fairly well and took lier food naturally. Rhinorrhcea was profuse, Ijut the nostrils were not completely blocked ; nor was membrane seen in that situation. The exudation on the left side of the fauces was iji process of separation. The e\'ening temperature was 99-8" Y. 104 DIPHTHERIA. Novemler 19 -i-Jfc /,/ '.4. , :<^'l Fig. 24. Fig. 2.5. tonsil ; the exudation which remained had a shrunken appear- ance (Fig. 24), Membrane apparent in both nostrils. The factor continued. At night the temjjerattorc was 99'6" ; ^>»/.sv, 120. A considerable mass of dirty-looking membrane still remained on the uvula., left tonsil, and palate, which continued to be hannorrhagic ; some came away during the day. Copious ,sero-sanguineous discharge from the nostrils was observed ; Init the fcctor was less. Decciiihcr V-UJi. — TcmjicreiJ iire, 99'4: ; jmlsc, IIU. The iii'ine passed in twenty-four hmirs was 19 ounces, and contained jVth io6 DIPHTHERIA. albumen. Boivels contiued. Tongue dry and blood-stained. The fauces were covered with dirty l:)ro^vn mucus, but only a small quantity of membrane was apparent. December lifJi. — Temperature, 99-2° ; 'pulse, 108. The urine contained | albumen, and the total quantity passed was 19 ounces in twenty-four hours. A thin layer of membrane was present on each tonsil. Marked reduction in the swelling of the lymphatic glands, nasal discharge, and foetor have ceased. December 16th. — A large ecchymosis is noticed on the abdomen o\'er the site where the serum was injected. Temperature, 98'2° ; pulse, 104. Decemher V.)lh. — I'cuipcrature, Q8'' : jndse, 100. Tiie ecchymosis has nearly disapi^eared. December 2lst. — Siupprcssion of urine since 6 p.m. on the previous evening. Tcvtjxratui'e, 97'4" ; almost pulseless at the wrist. Tongue dry and brown. Pupils contracted. Drowsy. Death occurred at 5.10 p.m., no urine having been voided for the last twenty-three hours. Treatment. — Two injections of antitoxin (B. I. P. M.) were given ; one of 20 c.c. on December 11th, and a second 10 c.c. on December 12th. The fauces were painted with Loettler's solution. No autopsy permitted. Case 3. — Faucial exudation ; recovery. Fig. 26. A female child, tet. 13, admitted November l^th with sore throat and vomiting which had occurred two days previously. ]VIeml)rane was seen on tlie left tonsil and uvula, proved haeieriu- KECOKD OF ILLUSTKATWE CASES. 107 UiijixiiUij to l.ie almost pure cliphtlieria,. Tcuqierain re, 98 ; 'j'mlsf, 104. A trace of allnunen diseovereil in the urine, which was Tree in rpiautity. Cervical glands ou left side slightly eidarged. Noi'Cmhcr 'loth: — Still inenilirane ou left tonsil; characteristic raw surface, with lucniorrhagic and ulcerated spots ou Ijoth tonsil and u\'ula,, where the exudation has recently separated (Fig. 26). The child, who was treated with antiseptics locally and iron tonics internally, made a good recovery, with slight palatal paralysis. Case 4. — Lacn ikh- ilijjJitlii'rin : rnvvcrii ; tunsillotoiii ij tlircc iiwntli^ Inter ; fieeijndurii e.''iid(iilori ; tdtenueited Jieicilliis ; reeoreri/. A man aged ^o years. Admitted to hospital on No\'endjer 8th, 1894. Fig. ~7. Previous History. — The patient had been subject to sore throat and had suft'ered from one attack of rheumatic fever. His resid- ence was believed to be healthy, bait a case of diphtheria had occurred in the house some years ago. The present illness began on the day before admission. On admission the whole fauces were of a deep red colour, the uvula, which was long and intiamed, clinging to the right tonsil which was greatly enlarged, with an inflammatory thickening of the corresponding anterior pillar projecting as a somewhat flattened ridge-like tumour far beyond the middle line (Fig. 2*7). On its surface were several widely open and deep lacuiuc, some co\'ered with the ordinal}' }'ellow caseated secretion of acute lacunar loS DIPHTHERIA. tonsillitis. Beyond this were several patches rather between than on the lacunar openings, of pellucid exudation not difficult to remove, nor when removed leaving a 1 deeding surface. The left tonsil was less enlarged and inflamed ; it exhibited but one blocked crypt (Fig. 27). The case presented all the clinical features of Acute Lacunar Tonsillitis, of a prol>al)Iy insanitary origin, in a patient the suliject of chrc.inic tonsillar hypertrophy. A culture was made from the light tonsil. The swab went deeply into several large lacun;e, which appeared to confirm the J J ■ \ /\ / //i \ -. / «i6 / Fio. diagnosis at the l)edsidc. The bacteriological repiirt, however, demonstrated that the Klebs-LiielUer fiacillus was present, the organism being of the long variety (Fig. 28). In the light of this report the case was taken as an example of lacunar diph- theria as first noted liy Jacolji, Ijut only recently confirmed l)acteriologically l>y Ko])lik. The fcmpei'dfurc on admission was 101-(S ; on the following day, N' "' 'V'......-- -,?;.'■ ' ■;■?■"■ -?""<■■ _i>>.-.../ ^ '^ ^ Fig. 30. Tig. 31. times vagniely described as "Involution" forms of the 1>acillus diphtheriie (Fig. 31). Furtlier cultures failed to develop the Itacilli, though the cocci multiplied in profusion. The throat gradually cleared, and later swabbings did not reveal any e^'idence whatever of diphtheria bacilli. CLASS TI. r.Ar'lLLUS DlPHTHERLl': WITH STUEPTOCOCCaS. Case 5. — SI iijhi faucial exudation; acdte crrrical crllvlifis; nasal iJipliflii:r'u(, iiroliaUy 'post-scarlatinal ; dcatli. A female child, aged 3 years, admitted on Novembier 3rd, 1S94, on the eleventh day of the disease. Previous History. — The child appeared to lie very ill on (.)ctoV)er 22nd, the date on which her throat first became sore and inllanuMl; on tlu.' following day au erythematous rash was RECORD OF ILLUSTRATIVE CASES. Ill observed on the trunk and limbs, and the next day Ixith sides of the neck under the angles of the jaw were swollen and tender. Five weeks previously a sister 5 years old had been attacked with sore throat and discharge from the nose. No rash had lieen observed, and she had made a good recovery. On admission. — The throat was inflamed. A thin film was seen on lioth sides of the fauces. There was a large dirty cavity in the right tonsil. Membrane was present in ))oth nostrils. Both sides of the neck were extremely enlarged and inflamed, giving the Cou ■proconmdairc of the French, and resemliling a -s t »>«i V -'■■■■ Fig. 32. severe attack of Angma Ludovici. Slie was semi-delirious. Tlie temperature was but 98", and pulse 104. The bacteriological examination showed profuse small colonies, which microscopically demonstrated the liacillus diphtherite in small numbers, associated with streptococci in chains of four or five segments, and of Batallion arrangement with numerous dis- jointed cocci, single and in pairs (Fig. 32). November Ath. — Delirium persists. The urine contained a haze of albumen. Tempemture,100'4:° ; pulse,106. Death occurred at noon. Treatment. — Local antiseptics and douchings of the mouth, poultices, and stimulants. 112 DIPHTHERIA. Case 6. — Severe nasal dipJithcria, 'pi'ohahly ijost-scarlatined ; death. A male, aged 13 months, a brother of the patient whose case has just been descrilied (Case 5). Admitted at the same time as his sister, on November 3rd. His mother stated that he had been subject to head-colds, and was a mouth-breather from his birth. On admission. — November ?)rd. — Very pale, and of waxy com- plexion. Profuse sere -sanguineous discharge from nostrils, in which mejnbrane was seen. There was epistaxis on the right side, and several petechiie were observed on the face. Tcmfeva- ?■«?¥, 100-2° ; 7w/.se, 78. . ■ ^,y;F--^. >:, ^r ■->' t Fig. ./ The bacteriological examination demonstrated profuse small colony growth of the diphtheria bacillus, a small form and a larger one staining markedly at Ijoth poles; associated with streptococci in chains of four or five elements, arranged in hatedlion form (Fig 33). November 4tk — Almost moriliund. Tcmjxred.ure, 99°; 2^}dse, 82. Died, 7 p.m. Treatment.— Antiseptic douches to both fauces and nares, with stimulants. Case 7. — Tonsillar camdedion; adenitis; senna treedment ; slight ■paralytic serfiela: ; recovery. RECORD OF ILLUSTRATIVE CASES. 113 A female child, aged 6 years, admitted on December 8th, 1894. On the previous day was taken ill with sickness and sore throat, the neck being swollen on both sides. Has l^een a month- breather since birth. On admission. — Both tonsils were enlarged and covered with membrane, the nvula lieing hidden by the swollen glands. Breath Fig. 34. Fig. 35. i-i ! K ■ .^-' '^■h • ' "^ Fig. .36. fetid. Cervical glands on both sides enlarged (Fig. 34). Temfptra- turc, 98-4" ; pulse, 100. Urine contained no albumen. Deeeinhcr 9th. — Slight cyanosis. Eight tonsil still overlaps antl hides uvula. The tissues bleed freely on attempting to remove membrane. Fcetor continues. Urine passed amounted to 34 oz. in twenty-four hours. No albumen. Temperature, 97'4" ; pulse, 122. H 114 DIPHTHERIA. The bacteriological examination demonstrated two main forms of growth, one white and discrete, the other semi-translucent. Microscopically, the bacillus diphtherise and streptococcus pyogenes were shown to be present (Fig 36). December IWh. — Membrane whiter and rolling up at edges, separating at centre ; f oetor continues. Complexion ashy and waxen. Restless, bowels confined. Glandular swelling subsided. Urine, 18 oz. in twenty-four hours. No albumen. Temperature, 100-4° ; pulse, 136. December 11th. — Eight tonsil is still very large, the left one is smaller. The membrane is gradually separating, clearing, rolling off, so to speak. It is much whiter, much thinner, and more transparent. There is no fcetor. Urine passed, 18 oz., contains a trace of albumen. Temperature, 98'4°; pulse, 110. December 13th. — Tonsils continue enlarged, covered with a layer of pultaceous secretion. The glands are shotty on the left side. Urine (19 oz. in twenty-four hours) contains a haze of albumen. Temperature, 97"4° : pulse, 108. December 15th. — Membrane almost gone, except a slight portion on the right tonsil. Appetite good. Temperature, 98° ; pulse, 100. The child made a good recovery. Only slight paresis of the palate and ciliary muscles were observed ; these soon disappeared. Treatment. — One injection of antitoxin (B. I. P. M.), 20 c.c, was given on December 9th, and the usual antiseptic swabbings and douches were employed. Later, nervine tonics for the sequelte. Case 8. — Faucial and nasal exudation; adenitis; serum treat- ment ; anuria ; recovery. A female child, aged 6 years. Admitted December 11th, 1894. Previous History.— The patient was the sister of the little boy referred to in Case 2, and was removed to the hospital on the same day. All the children at their home, six in number, slept in the same room. On December 9th the patient was taken ill with sore throat and vomiting. On admission. — Neck was swollen on both sides, and very painful. JiECORD OF ILLUSTRATH'E CASES. "5 Large masses of iiiembi'aiie were seen on l)Oth tonsils, wliicli were \'ery swollen and completely concealed the uvida. ilendnane also diagnosed in post-nasal space. Ti'inpfratiirc/.)?,--^''] pnlsc, 12S. The bacteriological report stated that, on cnltnre, colonies of the hacillus diphtheria' were ex'ident, and microscopically the presence of the diphtheria bacillns associated with streptococcus py(igenes was demonstrated. Deniithcr I'ltli. — A large mass, o\-er .'3 inches long and 2 inches in circumference, was removed with forceps from the nares. No Inemorrhage followed. Later in the day the mendjrane was seen to lie se}iarating from the fauces, crackling away as it were, )jut the uvula which is now visd)le is seen to Ije \erj thickened, covered with exudation (Fig. •"■7). iMendjrane seen in nostrils. I'rine Fig. 37. passed was G ijz. in t^velve lioui'S ; it contained a hea\'y trace of albumen. Temperature, 98'4:" ; puhc, 120. Beeemher I'-itJi. — The right tonsil presents a red and almost raw appearance, the membrane has almost gone except a thin layer on the left tonsil. The u\-ula is large and covered with membrane which is separating and leaving spots of exposed mucous mem- l.irane. The glands are still slightly enlarged, especially on the left side. Eleven oz. of urine passed in twelve hours. Teniperaturc, 98-4" ; p>vJsc, 108. Dccemhcr lotJi. — Throat nearly clear of memlirane. Thirty oz. of urine passed in twenty-four hours ; a trace of albumen. Tongue clean. Food taken well. Patient \'ery bright and cheerful. Tcmpcrafiire, QS'-i' ; pulse, 108. She made a very slow recovery, Il6 DITHTHERIA. being subject for many weeks to paroxysms of cardiac weakness with marked cyanosis. Treatment. — One injection of I'O c.c. of antitoxin (B. I. P. M.), and tlie usual local antiseptic applications. CLASS III. Bacillus Dipiitheele, with Steepto- and Staphylococcus. Case 9. — Tonsillar exudation, vnth ulceration; jrrohahly scarla- tinal ; recover//. A male child, aged 6 years. Admitted to hospital on JVovcmber 10th, 1894, having suffered from sore throat since Octolier 28th. / ■>,. ", .:,•■■'. '\-yt ,X' ', * * V^ { ,7 >v' >/ ' - - ■ * > ^'-r-V*- i '•■ i ■k;. lis. ■■■'-' rV On admission. — His countenance was ]iufiy, and rather characteristic of scarlet fever ; but no distinct liistory could be ascertained of a rash, nor of peeling. Skin was dry, and tempera- ture 9r F. The fauces were seen to 1je inHamed and dirty-look- ing. An excavated and exudation-covered idcer was seen on the right tonsil ; there was sliglit enlargement of the glands on each side of the neck. These could lie felt as separate small nodules and were not quite typical of tlie adenitis of diplitheria. Allnmien was present in tlie urine to the auKjunt of -^Vth. RECORD OF ILLUSTRATIVE CASES. 117 Bacteriological examination showed colonies containing a few bacilli of diphtheria; the main mass consisted of strepto- and staphylococci. The photo-micrograph (Fig. 38) shows but few of the associated cocci, due to inadvertence in selection from the slide of the ex- hibited area. The patient recovered. Treatment. — Antiseptic swabbing, and douches. Iron and chlorate of potash mixture given internally. Case 10. — Faucial and nasal exudation ; tendency to hcemorrhagic form ; cervical adenitis ; serum treatment ; anuria ; death. A male child, aged 6 years, admitted December 26th, 1894. The history was that he was taken ill on December 23rd, the initial symptoms being sore throat and vomiting. On admission. — There was extensive exudation on both tonsils, uvula, and soft palate. The tonsils were very large, and bled readily when touched. Both nostrils were blocked with mem- brane, and there was profuse nasal discharge, accompanied by great fcEtor. The neck was much swollen on both sides. The com- plexion was grey and earthy-looking. The urine, of which 14 oz. was passed in the first twelve hours, contained much albumen. Temperature, 99-8° ; ptdse, 136. Bacteriological examination demonstrated the presence of the bacillus of diphtheria in association with streptococcus pyogenes, staphylococcus, and other bacteria. December 21th. — No urine passed for nine hours. Patient very restless, breathing laboured. Lips and tongue very dry. Throat condition remains the same as yesterday. Temperature, 100-2° ; pulse, 156. At 8 p.m. almost pulseless. A very small quantity of urine was passed in bed. Death occurred at 9.15 p.m. Treatment. — Two injections of antitoxin (B. I. P. M.), one of 10 c.c. ; the second 8 c.c. of Behring's; diuretic mixture, antiseptics, &c. iiS DIPHTHERIA. Case 11. — Faucicd, pofit-nusal, and laryngecd exudation ; serum treatment; anuria; death. A male child, aged o years, was admitted to hospital on Deeemher Stli, 1894, having snffered from a sore tlu'oat since Heeemljer 3rd, followed by swelling of the cervical glands on Decendaer 6th. On admission. — Membrane was seen on the left tonsil, extend- ing somewhat to the soft palate. There was also a small piece observed on the right side of tlie uvnla (Fig. 39). Ou turning up the tip of the latter, memljrane was seen on tlie posterior surface, ■.*•■■■■ 1\- •> ■i-iS -•% Fig. yu. I'^iG. 40. and witli the laryngeal mirror, on the tip of the epiglottis. The temperature was 97'8 ' ; jruJ.se 100. Deeemher 9th. — Tlie face was ]iuft}'. A vesicular erudition resembling that of acute eczema was observed under tlie angle of the right jaw. Ternperidure, 97'8' ; paJse, 100. Bacteriological examination slKJwed a profuse growth, evi- dently ci imposed of se\"eral i.irgauisms, most prominently strep- tococci and staphylococci. Microscopically, staphylococcus, alljus ami aureus, dijilocdccus, streptococcus (of marked batallion arrangement), and liacilli resendiling the so-called "involution forms" of the liacillus di]ilitlieri;c were demonstrated (Fig. 40). RECORD OF ILLUSTRATIVE CASES. 119 Note. — It is believed that the usual precaution against making a culture witliin reasonable time of employing antiseptics was over- looked in this case. Hence the unsatisfactory character of the report as to the bacilli. December 10th. — No urine passed for nine hours ; but, from the state of the sheets, some was believed to have been voided during the night. The eruption has disappeared. The face is not so puffy. A'ery restless, little or no sleep during the past twelve hours. No urine passed for eighteen hours. Tcm'pcrature, 97-8° F ; pulse, 136. Died at 7 v.^i. in the evening. Treatment.— Antitoxin (B. I. P. M.) 10 c.c. Local antiseptic, swabbing, and douching. Case 12. — Diplifherict vjitJiovt exiuleition on fauces, and vnflo negative cliagnosis of bacilli ; Otorrhwa on twelfth day, with jJresence of bacillus ; serum treatment ; recovery. \ 1. , ,* \ * 1^' ** •r •v Fig. 41. A female child, aged 2 years, admitted to hospital on January 23rd, 1895, on the third day of the disease. On admission. — No membrane was observed in the throat, nor was any present during her residence in the hospital. The tonsils were large and the neck swollen. Tcmjierccture, 102°. 120. DIPHTHERIA. The bacteriological report was negative, no diphtheria bacilli being demonstrated. The only organisms present were strepto- and staphylococci. 10 C.C. of antitoxin (B. I. P. M.) were administered, and the temperature, after a slight rise, fell to 101° F. February 4th, the twelfth day after admission, after a slight rise of temperature, a muco-puruleut discharge was noted from the right ear ; not painful. February 6th. — A similar discharge was present in the left ear ; without any pain inside or outside the meatus. A culture was made from the otorrhoeal discharge on the first day, before any local treatment of the discharge was commenced. The bacteriological examination demonstrated diffuse, greyish- white colonies, with a few points of a lighter colour. Microscopi- cally, the presence of the bacillus diphtherise, associated with strepto- and staphylococci, was detected. The patient made a good recovery, but developed palatal and ciliary paralysis. February 11th. — Temperature, 100'8° Some adenitis. March 21st.- — A haze of albumen for twenty-four hours. March 25th. — Palatal paralysis. Treatment was chiefly directed to irrigating the throat, and, later, syringing the ears with boracic acid lotion. One injection of 10 C.C. of antitoxin (B. I. P. M.) was given on the day of admission. CLASS IV. Bacillus Diphthbei^, with Streptococcus and Diplococcus. Case 13. — Fourth attack of diphtheria ; tonsillar exudation ; re- covery, with grave paralysis. A female aged 40. Admitted to hospital October 2,1st, 1894 Previous History.— The subject of chronic albuminuria. She had been for eight years a nurse in an infectious fever hospital, and during the last three years, including the present occasion, had been attacked four times with diphtheria. One of her pre- RECORD OF ILLUSTRATIVE CASES. 12,1 vious attacks of diphtheria was followed by slight paresis and iliplopia. On admission. — Membrane was present on l)oth tonsils. There was slight glandular enlargement. Temperature, 100'4' ; 'puhc, 88. November 4:th. — The condition of the throat was characterised by extreme anaemia, except at the parts attacked. There was thickening of the fances, and the pillars of the tonsils were merged — as often seen at this period in the life of a patient who has been the sul:iject of chronic tonsillar hypertrophy. There was only one small thin i)ellicle of membrane on the •A N K v-r ■ ^^7 '^4 Fig. 42. right tonsil, and this was completely removed by the swab, and was the source of the culture. The bacteriological report was that the culture showed a pro- fuse growth of small heaped-up colonies ; the bacillus diphtheii;e was present, associated with streptococcus and diplococcus (Fig. 42). November 5th. — ISTo membrane to be seen. The temperature was subnormal, and the urine contained aljout ^^th albumen. November 11th. — The palate and fauces were very auiemic. Temperature subnormal Urine contained a heavy haze of albumen. November 15th. — Patient complained of pain in both legs, and on examination the knee jerks were found to be slightly exaggerated. 122 . DIPHTHERIA. November 25th. — Some loss of power in left hand and arm; knee jerks exaggerated; she has some difficulty in walking, and drags her feet. Some diplopia noted. JSTo albumen in the urine. For a few days past the patient has been assisting in nursing scarlet fever cases. It suggested itself to us that, as the patient was engaged in the wards, the micro-organisms were constant inhabitants of her throat, but the probability of such an hypothesis was disproved by a culture taken on November 26th, at the end of the fourth week of her attack. The bacteriological report of this later culture was that no definite growth of any sort could be seen, and under the microscope only a few micrococci of indefinite character were observed. The case, therefore, appears — as far as the fourth attack is concerned — to be one of genuine re-infection. We may add that already grave paralysis of limbs and sight are super- vening. November SOth. — The loss of power in the left arm and in both legs still remains ; diplopia continues. The urine contains nearly :|th albumen. The patient was subsequently superannuated, the paralysis not having disappeared at the time she left the hospital. Remarks. — It is sufficient to note the bacteriological confirmation of the clinical diagnosis of a fourth attack of true diphtheria in one individual, and at such frequent intervals. Her chronic kidney disease and night duty were probably exciting factors, and as the after history proves, paralytic symptoms have supervened, which leaves no clinical doubt as to the nature of the case. Another point of interest is that here is a case in which recovery from diphtheria has four times taken place in a very unpromising subject, and in that complication of diphtheria characterised by the presence of both the Klebs-Loeffler bacillus and streptococcus, said by some authors to be invariably fatal, and recorded in the clinique of Eoux as having been fatal in thirteen out of fourteen cases. RECORD OF ILLUSTRATIVE CASES. 123 CLASS V. Bacillus Diphtiierli': and Diplogoccus. Case 14. — Ahindant tonsillar dcpodt ; ■paralytic sciiudce ; recovery. A female eliikl, aged 5 }'ears, atlmitted to liospital November 10th, 1894. The parents stated that the patient was taken ill (}n November 7th with sore throat. There was no sickness, and no cutaneons rash had lieen observed. On admission. — Tiie throat was very inflamed, with a thick Fig. 43. Fki. 44. plaster of deposit of membrane on both tonsils ; the uvula being unaffected (Fig. 43). The skin was very dry. A haze of albumen was present in the urine. Temperature, 98" F. Bacteriological examination demonstrated numerous small colonies of a milky white growth. Microscopically, the Ijacillus diphtheria? was shown to be present in great abundance, with some diplococci (Fig. 44), only a few other organisms being visible. November 12th. — The cervical glands were eirlarged on both sides. 4 124 DIPHTHERIA. The exudation was thinner, and of a pearly colour ; the throat was less inflamed. Temperature, 100-4°. November lAth. — The membrane was still present in very pellucid patches on the tonsils. Temperature, 101° November 25th. — The child doing very well, and her general condition very satisfactory. Membrane, however, still present on the left tonsil, and on the right anterior pillar of the fauces. It has a dirty appearance, unlike the pearly tint formerly observed. The cervical glands are still slightly enlarged, and the urine con- tains a trace of albumen. Temperatitre, 98 '4°. December 9th. — Throat quite clear of membrane. The patient has had strabismus and diplopia for the last four days. She eventually made a good recovery. Treatment. — Antiseptic swabbings of the fauces, syringing the throat with boracic acid lotion. Iron and chlorate of potash internally. CLASS VI. Streptococcus. Case 15. — Pseudo-diphtheria of scarlatinal origin ; recovery. A female, aged 29 years. Admitted to hospital on October IZth, 1894, seven days after the initial symptoms occurred. Previous History. — On October 8th she was taken ill, the first symptom being severe headache, followed by severe sickness and diarrhoea. On admission. — The throat was inflamed and membrane seen on both tonsils. The urine contained a trace of albumen. Temperature, 104'6° ; pulse, small, 112. October 2*lth. — Desquamation commenced. The urine still contained a trace of albumen. October 2%th. — Desquamation general all over the body. November 4th. — Some membrane was observed on the left tonsil (a second manifestation). On removal of a portion of this exudation, a slight trace of haemorrhage occurred. RECORD OF ILLUSTRATIVE CASES. 125 Bacteriological examination showed an almost pure cultivation of streptococcus, which microscopically appeared to be arranged in flexuous chains, consisting of from four to eight elements (Fig. 45). ^ *?w^ » > • f > \ ■^ * . / Fig. 4.5 Treatment. — Baths, and inunction of eucalyptus oil to the cutaneous surfaces during the period of desriuamation ; antiseptic gargles to the throat ; diuretics internally. The patient recovered without any paralytic or renal secpiela?. Case 16. — Pseudo -diphtheria of _^jro&ff&/_y scarlatinal origin ; recover)./. A female, ret. 101, who was attacked witli sore throat on Novcmher 2nd, 1894. The neck and glands under the jaw became swollen on ISTovember 5th, and she was admitted into hospital on November lltJi. The throat manifestations consisted of intiammation, deeply excavated and vertically parallel ulcers of the tonsils, with dirty greyish and pultaceous patches on the surfaces. The uvula was red, with slightly opalescent exudation on the left side (Fig. 46). Sub-maxillary and cervical adenomata. Temperature, 99°. Urine exhibiting haze of albumen. Although there was no history of a rash, the case in many 126 DIPHTHERIA. respects was one of scarlet fever. The diagnosis was fsaulo- dipldhcria. A culture was made on November lotli, and the following was the report of the bacteriological examination : — J ■ / Fig. 46. Fig. 47. (Drawing-.) The growth consists entii'ely of streptococcus, and, as the drawing shows, in long lle-\uous chains (Fig. 47). Treatment. — Local antiseptic douches ; chlorate of potash confection, and iron internally. A good i-ecovery was made. CLASS y\i. Streptococcus and Diplococ(;its. Case 17. — I'sendo-diphfJK'ria, and j/)f/'(Yfi«.s/////w of insanifary orif/in : 'irrurcri/. A niale, a't. 4'2. Admitted on Novcmhcr 5tJi, on account of a. sore throat, from wliich he had been suffering for twenty-four hours, with general malaise. There was a rJondii, almost memliranous, a];>pearance of tlie fauces, which were much thickened and covered witli a creamy secretion. 'J'here was also inilammation of both tonsils, wliich wei'C not enlarged. The soft palate and uvula were also inflamed. RECORD OF ILLUSTRATIVE CASES. 127 the lattev being ttHlematous and translucent. Tcuvpcrnfinr, 100" F. ; 'pulsc, 110. The diagnosis was that of insanitary /(mcitis And jfciitonsiJIitis. A cnlture was made from the tonsils, and the bacteriological report proved the presence of strcptvcom and a few iliplocorci. In ^-^-"^ ■ r .*»•!•. / • -^'ix / ■v.^ / ., -..x * ' \ .'■" ■" ■ '\ .> * .. ' \ »• i. > " .\ \ 1 V' I ^ 1 -••■•■■■ - " '/ \' '. ,/ \ :.■■■- ■■■• / \ ■ r .. « "x ■ -'■■ ' ' -:/ -'' ■ .- '^^ Vu; 4S. this case the streptococci were of the short, rigid, or least virnlent variety (Fig. 48). Treatment. — A mixture of mercuric hiniodide, and carbolic gargle. Good recovery. CLASS VIII. Staphylococcus. Case 18. — Pscndo-iJiphthcria aKompanyimj typhoid fcrcr ; death. A male, a't. 27, who was taken ill nine days before admission, with pain in the back and sore throat. He was admitted on Novcmhcr bth with notification of diphtheria, with membrane on the uvula and tonsils. Tcmpci'aturc, 101-4°. Enteric spots were discovered orr the abdomen, and he passed typhoid stools. Between Novendjer 5th and November 11th the temperature rose to 106". The fauces and uvula were of a deep red colour and DIPHTHERIA. covered with membrane, especially on the right side up to the junction with the palate. From a culture made on ISTovemlier 11th, the following was the bacteriological report : — Numerous yellowish white colonies, tending to coalesce and form streaks. Microscopic examination showed an almost pure specimen of staphylococci, with a few cocci arranged in pairs, and a few bacilli, probably not those of diphtheria. Independently of the fact that there were no colonies resembling those of the Klebs-Loeffler organism to be seen in the culture tube, the bacilli in the slides were much smaller than those of diphtheria. The patient died on November 13th from collapse following on perforation of the bowel. Case 19. — Pseudo-diphtheria ; exudation on fauces and uvula ; recover I/. (,' .. .-./f Fig. 49. Fig. 50. A female, ;et. 40, who was taken ill with sore tliroat on November I7th, 19.~-NoN-BACiLLATtY Cnnurous Membrane ritoM the Trachea. Staphylococci with a few Streptococci in. situ. iiienibrano from the lirouchi tn the larynx, has also been described, but it is ditiicult of proof. Tn any case it must lie rare. Wiien non-baeillary. Croup has lieen asserted by Dieulafoy, in his ratliologic Interne (Vol. II., 1894), to lie due to the presence of little cocci, which present themselves in groups of two, and from his description a,nd allusion to their discovery by Eoux and Ma.rtin, he evidently identifies them with the " ISrisou coccus" of those authors ; but why pseudo-diphthcrial croup should lie attri- liuted only to this particular niicro-orga,nism, it is somewhat difli- cult to nu.lerstand, sinc(' these cocci play but an unimportant role in faucial iidlanunatinns. Dioulafoy further stales that pseudo- LARYNGO-TRACHEAL DIPHTHERIA— CROUP. i8i membranous laryngitis, due to strepto- and pneumococci, has no tendency to penetrate and grow in the larynx. Klein and Councilman similarly select the streptococcus as the particular organism of pseudo-diphtherial croup, but the accom- panying illustration of a false membrane in the trachea, from a beautiful preparation made by Dr. Taylor Grant while in Eoux's laboratory, proves that staphylococci as well as streptococci (Fig. 59) may be responsible for the membrane, and may penetrate in exactly the same manner and to the same extent as the bacillus itself. Indeed, there appears no reason why, in the case of an extension of the membrane from the fauces to the larynx, the coccus should be assumed to change its type. The following is a case illustrative of pseudo-diphtherial croup, of strepto-staphylococcal origin : — F. H., male, aged 3 years. Admitted to hospital February 17th, 1895, at 7 P.Ji., having suffered from cough and sore throat since Mth. No fact could be elicited pointing to the possibility of a scarlet fever infection. Albumen was present, but at no time was more than a haze. On admission, membrane was seen on both the tonsils and soft palate. Croupy cough and marked ensiform retraction suggested laryngoscopic examination, when membrane was seen in the larynx. 20 c.c. antitoxin (B. I. P. M.) injected. Bacteriological examination, from cultures made on admission, showed strepto- and staphylococci, but no diphtheria baciUi. This examination being doubted, another was made on the 21st, hut likewise failed to reveal diphtheria bacilli. February \Wi. — The temperature had fallen to 984. The breathing was easier and without stridor. Sternal retraction less marked. Exuda- tion had neither diminished nor increased. Antiseptic irrigation also prescribed. Evening temperature 102°. February \%th. — Temperature and general condition much the same. March Zrd. — A rash was noted, which disappeared within twenty-four hours. March 13th. — Death. Necropsy re'vealed the following : — Lower lobes of lungs airless, especially on the right side ; evidences of broncho- pneumonia in the middle lobes. A soft membranous exudation, extend- ing from the lower surface of the epiglottis along the larynx and trachea, so as to make an almost complete pulpy cast of this tract. Similar membrane was seen to extend into the left bronchus. 1 82 DIPHTHERIA. We are inclined to agree with Fraenkel that non-bacillary croup may sometimes be infectious, especially when strepto- or staphy- lococci are present in the exudation, as also with the opinion of the same observer, that true diphtheria is liable to follow oia a croup of an originally non-bacillary nature, more so, probably, than in the fauces. The inflammations of the larynx, which take place as secondary results of some of the exanthemata and specific fevers, may also be non-diphtherial. Sidney Martin, in 1892, expressed the opinion that " there is no evidence at present of any disease other than diphtheria which can produce a false membrane in the larynx." Euault, writing in the same year, believes that, in the great majority of cases, bacillary croup is consecutive to a true diphtherial condition in the fauces. But Billings (1894) has found that of 286 cases in which the membrane was confined to the larynx and bronchi, 80 per cent, proved to be true diphtheria, only 14 per cent, being undoubtedly not diphtheria. This last view is in entire agree- ment with our own conclusions, not only as to fact, but to frequency. These opinions and statements refer especially to those cases in which croup is due to micro-organisms ; but false membranes of essentially the same macroscopic and microscopic character as those of truly diphtherial origin have been reported as produced on the mucous lining of the buccal cavity and air-passages by every kind of traumatism, as, for example, irritant poisons, solid, fluid, or gaseous, scalding water, scorching heat, chemical or galvano-caustics, or even strong Eau-de-Cologne. Oertel per- formed the experiment of dropping a few minims of liquor ammonise into the trachea of seventeen animals, and succeeded, in every instance, in generatuig an artificial croup. There are still many practitioners, whose opinions are entitled to respect, who hold that croup may be the result of exposure to atmospheric causes, such as intense cold, and quite independently LARYNGO-TRACHEAL DIPHTHERIA— CROUP. 183 of any microbic infection, but in the light of advanced bacteriology both traumatic and atmospheric causes must, in the future, be held to be only predisposing. With regard to the morbid anatomy of non-bacillary croup, a special distinction has been made that in true diphtheria the exudation is poured out, not only on the superficial portions of the mucous membrane, but that it also invades and penetrates the lymphatic spaces, and so reaches the deeper parts of the regions attacked: Weigert has enunciated that in true diphtheria the deeper tissues are involved in a necrotic process. Our microscopic sections hardly warrant us in accepting these distinctions as of uniform application. In the supra-glottic region, false membranes are as firmly adherent as those in the fauces, but they become thinner and less adherent the lower their site in the air-passages. In the minute bronchi they are almost fluid. The bacilli and other organisms also become less numerous. Our position with regard to the pathology of croup having been thus defined, further remarks will be directed to such changes in the symptoms and treatment as shall depend on anatomical site and its inhibitory influence on the performance of vital functions. Symptoms. — The onset of primary croup may be heralded by those general prodromata common to diphtheria of the fauces, but more usually croup occurs as an extension from the fauces, to be witnessed on the third or fourth day. The difference in situation results in functional disturbance, which, according to Barthez, may be divided into three successive stages, the first characterised by cough and hoarseness, the second by aphonia and paroxysmal dyspnoea, and the third by suffocation and asphyxia, ending in death. Between all these there is no hard and fast line, and indeed very many cases never go beyond the first stage, in which circumstance Ruault employs the term abortive croup. Group begins with a small, dry, and frequent cough, which has a high-pitched, metallic, and ringing sound, generally denominated i84 DIPHTHERIA. brassy and laryngeal, but is liable to become gradually muffled and even noiseless. Change in the voice is another and sometimes the first symptom. Beginning as a simple catarrhal hoarseness, it is soon observed to assume a metallic timbre and to be raised in pitch. When mem- brane is abundantly manifested on the cords, complete aphonia may ensue. This phenomenon may also be explained by paralysis of the adductors. This may be merely functional, or due to diphtherial neuritis and myopathic changes. Sometimes there is slight pain in the region of the larynx. Embarrassment of respiration quickly supervenes, the movements increasing in rapidity to thirty-five or even forty per minute. There now occur attacks of paroxysmal dyspnoea of the most painful and alarming character, and these may commence so soon as a few hours after the first warning that there is anything wrong. Each inspiration is attended by a peculiar stridor, which con- stitutes one of the most marked characteristics of the disease. This stridor has been variously described as high-pitched, piping, shrill, metallic, sibilant, and wheezing. During the dyspnoea there is indrawing of all the muscles of the supra- and sub-sternal regions, as also of the epigastrium, the false ribs, and even the lower portion of the sternum itself ; of all those parts, in fact, which would generally be distended in healthy inspiration. All the inspiratory muscles, regular as well as auxiliary, are observed during the spasm to work painfully ; the dilated nostrils, the terrorised expression of the face, and convulsive movements of the limbs, all giving evidence of a laborious and futile struggle for breath. The complexion becomes cyanotic, and death from apnoea appears imminent and may even occur. Should membrane be coughed up there may be a favourable termination to the dyspnoea, when the metallic sound of the cough will be observed to change to that of a bronchitis or remitting laryngitis. Diagnosis.— Independently of the question of membrane in the fauces, the history of the attack, the absencL' of fever and cough, and the complete remission of all symptoms between the attacks LARYNGO-TRACHEAL DIPHTHERIA— CROUP. 185 which distinguish laryngismus stridulus, and the reflex cough observed in some cases of enlarged pharyngeal and faucial tonsils, are sufficient to prevent the graver malady being mistaken for the milder. Laryngoscopic signs. — In a case of average acute type, the larynx presents, at the onset, a diffuse red colour of varying intensity, and with some tumefaction of the mucous membrane. Later, there are seen here and there on the epiglottis, the ary-epiglottic folds, the inter-arytenoid commissure, ventricular bands, fine XDcUicles of membrane, which is at first of a brilhantly opalescent white (see Frontispiece). These become yellow or greenish in colour, and thick and opaque, with a tendency to spread over the greater part of the laryngeal vestibule, and finally to reach the vocal cords and the sub-glottic region. In other cases the larynx may be seen to be simply red, and to exhibit only a minute quantity of membrane, whilst the sub-glottic region and the trachea, so far as can be seen, are more or less entirely covered by fibrinous exuda- tion. Failure to discover membrane in the larynx by no means imphes that there is no exudation in the infra-glottic region. Often in examining a faucial diphtheria the membrane may be seen extending to the free edge of the epiglottis and no further; but these cases, as a rule, give no trouble from laryngeal symp- toms. In others, considered 'to have arisen primarily as laryngeal, membrane may have cleared away from the fauces before the air- passages have been attacked. Bretonneau attributes the cause of the dyspnoea to the mechanical obstruction of the exudate in the larynx; Jurine, author of Napoleon's prize essay, to a spasm of the glottis caused by the irritation of the laryngeal mucous membrane; Cadet de Gassicourt to a paralysis of the dilator nmscles and to the action on the medullary centres of the de-oxygenated blood. Euault is of opinion that Jurine's view is alone justified. JSTo doubt both the extent and density of the membrane plays a very important part in the obstruction, but a very small and thin pellicle of exudate is compatible with much dyspnoea and spasm i86 DIPHTHERIA. Such a case quite recently occurred in the hospital practice of my colleague, Dundas Grant. Actual nervo-muscular laryngeal paralysis is an exceptional, and cannot be considered the usual cause of dyspnoea, but when it does occur it probably involves the abductors rather than the adductors, because loss of phonetic quality is by no means uniformly synchronous with extreme dyspnoea, unless the vocal cords are themselves the site of membrane. The nasal voice, due to palatal paresis, is to be distinguished from changes in primary laryngeal tone. Not that we deny that the adductors are also and, indeed, mainly implicated, and this is often the cause of the aphonia, but in such case the respiratory difficulty is purely spasmodic, and consequently of a less dangerous character. Even when the dyspnoea appears to be entirely due to a mechanical obstruction of the air-passages by membrane, spasm is always superadded. Administration of chloroform during an attack of dyspnoea bears out this idea, as under its influence the dyspnoea diminishes or even disappears altogether. Of complications due to croup, acute bronchitis is very common. Fseudo-membranotLS bronchitis is rare, or perhaps one might say difficult of recognition, during life, since stethoscopic signs are uncertain ; the only sure sign of membranous extension to the bronchi is the expectoration of ramified casts of the tubes (Fig. 60), but, as previously stated, diphtherial exudation diminishes in fibrinous quality the lower it descends, and is often found to be of almost fluid consistence in the smaller bronchi. Broncho-pneumonia is to be recognised by well-known signs, and may generally be interpreted as evidence that the croup is either pseudo or complex diphtherial in character. Prognosis, course, and termination. — Even mild attacks of croup should give cause for anxiety, for neglect of a simple case has frequently been followed by relapse of the malady in an aggravated form, with a suddenly fatal termination. Age is an important element in prognosis, and the older the child the more favourable is the chance of recovery. LARYNGO-TRACHEAL DIPHTHERIA-CROUP. 187 The general elements of prognosis in faucial diphtheria apply equally to the laryngo- tracheal form, in which, however, there is an added danger of no little importance— viz, laryngeal obstruc- tion. When croup does not extend beyond the vestibule, it may remain latent, and recovery take place without having given rise to any symptom of distress, and even when it has advanced so far as the inter-arytenoid space, spontaneous cure is still possible, and such recoveries occur to the probable extent of 5 to 10 per cent. / Js Tig. 60. — Tkacheal and Bronchial Casts, from a Case of Diphtherial Croup. When the membrane extends further, and there is paroxysmal dyspncsa and aphonia, spontaneous cure rarely, if ever, takes place. But surgical intervention distinctly diminishes the mortality. In the course of the disease towards restoration to health, gradual separation of the membrane takes place, followed by free mucous expectoration, and diminution in the severity and stridulous character of the cough and respiration. In milder cases there may be no objective evidence at all of 1 88 DIPHTHERIA. membrane in the expectoration, the exudation having either not arrived at the stage of fibrinous deposit, or having become pultaceous before release. The duration of a case in its acute form is from four to ten days ; complete recovery being delayed to a month or five weeks, and in some instances being followed by one or more relapses. When the disease takes an unfavourable course, the paroxysms become more frequent and almost unremitting; the cough, although toneless, is more distressful ; the pulse-beats are more rapid, the little patient is more restless, and the extremities become cold ; finally they, as well as the countenance, become cyanotic. The fatal issue may occur in any of the following ways : by apncea, or by convulsions during a paroxysm of dyspnoea; by asphyxia through actual blocking of the air-passages with memr brane, otherwise carbonic acid poisoning ; by cardiac faihire, due to diphtherial toxaemia or to deposit of fibrin in the heart and great blood vessels ; by exhaustion and coma ; and finally, by secondary lung complications. The date of a fatal termination is seldom extended beyond the fourth or fifth day, unless tracheotomy has been performed, in which case, even if life be not saved, death may be somewhat delayed, and is more peaceful. Regarding the convulsive nature of the paroxysms, Ferriar (1798) has reported a case in which the struggle was so violent that after death, the corpse, in a great measure, rested on the occiput and on the heels. Treatment of Croup requires to be pursued with energy and discretion from the first. There is a general consensus of opinion in favour of an atmo- sphere hyper-saturated with steam ; but we are inclined to think that this treatment is often carried to excess. The bed should be curtained, and vapour brought near it by means of a steam-kettle, but the croup tent bed, which gives the little patient a continuous vapour-bath, is as unnecessary as it is depressing. LARYNGO-TRACHEAL DIPHTHERIA— CROUP. 189 If vapour is required to be brought nearer to the child's mouth, that purpose is best effected by a steam draught inhaler with plain water impregnated with pinol [Formula 23], or in the case of spasm with benzoin and chloroform [Formula 24]. This desideratum may be enhanced by the general inhaling of carbolic acid vapour from a steam-kettle placed near the bed, so that the patient may be said to live in such an atmosphere night and day. But as children are very liable to carbolic acid poison- ing, the effects on the urine should be carefully watched, or pinol, eucalyptol, or terebene be substituted. This measure, combined with internal administration of sedatives to allay spasm, is in many mild cases all that is required. In infants it may be impossible to apply local remedies to the membrane, except by a cotton-wool laryngeal brush introduced by guess work ; but in those older, by help of the laryngoscopic mirror and after the use of cocaine spray to allay spasm, one may some- times be able to detach it and apply strong antiseptic solutions. Of general measures of traditional repute there is, howeve];^, much to be said in favour of an emetic given at the first onset of an attack, and it is indicated on the ground that should membrane be formed in the trachea or bronchi, as is not unfrequently the case before the manifestation of laryngeal symptoms, an emetic may possibly favour its expectoration ; and even later when the larynx is covered with membrane the action of an emetic may help to detach pieces of it which are only slightly adherent. But a more profound reason for the salutary action of such an emetic as ipecacuanha is its moderately depressant eff'ect, by which reflex excitability and laryngeal spasm are diminished. But the main indication for this remedy should depend on the bacterio- logical examination, and should be contra-indicated where the diphtherial asthenia is at all pronounced ; in any case, it should only be employed in the early stages of the attack. The best form of emetic for a child from one to five years of age is a teaspoonful of ipecacuanha wine every fifteen minutes till vomiting is produced. igo DIPHTHERIA. The further general and constitutional treatment of croup is to be carried out on exactly the same lines as in faucial diphtheria. The cough and spasm should be allayed by chloral and ipecacuanha [Formula 6] ; inhalation of chloroform may be necessary in violent spasm. Of further local measures we prefer the continuous external application of cold by the Leiter coil, already advocated in the faucial variety. This application does not allow cold moisture to drip down the neck and chest, nor does it damp the night-dress and sheets as do cold cloths, or ice-bladders. On the other hand it is quite as easily retained as a poultice or stupe or sponge, and in the more recent form of its inventor is of no great weight. Whether for the purpose of I'cducing the inflammation, of modify- ing the spasm, or of favouring rapid separation of the membrane, application of continuous dry cold is preferable to that of moist heat, which is almost always followed by chill. Should warm applications, however, be preferred to cold, they can equally well be applied by the coil. We do not any more prescribe applications of solutions of nitrate of silver, so strongly recommended by Bretonneau, Niemeyer, and other older writers, nor indeed any other mineral solution ; for, however mild, such applications, especially the first-named, are provocative, not only of spasm, but of coagulation of the ordinary secretions of the mucous membrane. The use of the croup brush is also to be carefully avoided, unless the practitioner is quite prepared to perform tracheotomy immediately afterwards, for the forcible disturbance of membrane in small children is very apt to block up the narrow glottic chink, and so to lead to serious and even fatal suffocation, and this quite apart frpm the dangers of spasm. The same caution is to be observed in relation to attempts at intubation, which will be considered presently at greater length. LARYNGO-TRACHEAL DIPHTHERIA— CROUP. igi Operative Measukes for the Eelief of Croup. We have considered the question of the removal of enlarged tonsils, uvulte, and nasopharyngeal adenoid growths in our chapter on faucial diphtheria, hut in laryngo-tracheal cases some other operative procedure is required to prevent death hy asphyxia due to mechanical obstruction in the larynx. Which is it to be. Intubation or Tracheotomy ? To decide this, the first step is to make, if possible, a laryngoscopic examination, which alone can give us an adequate idea of the extent of surface involved ; and if the laryngeal mirror, as we have all along contended, is advis- able in case of diagnosis, it is indispensable when deciding on an operation, and it is not unnecessary to repeat that only those in the habit of using it are in a position to appreciate how much aid it can afford. One may rarely fail to see whether membrane is or is not in the larynx, and to what extent. The "gagging'' — which introduction of the mirror induces in young children who are the subjects of enlarged tonsils — is even an advantage in affording a complete, albeit only momentary, view, of which the expert will not be slow to avail himself. Success in the treatment of croup does not depend on the number of tracheotomies or intubations, but rather on the number of favourable results which are obtained without operation ; and the more expert the practitioner is in the use of the laryngoscope, and the more skilled in making intra-laryngeal applications, the smaller will be the number of occasions on which he will require to resort to operative procedures. Examination with the mirror may reveal the. presence of only a small piece of membrane removable by the laryngeal cotton- wool brush, the hand being guided by the reflector. Such a manipulation ought to be preceded by spraying the throat and larynx with a 5 to 10 per cent, solution of cocaine to allay spasm, and should be followed by the use of benzoin and chloroform 192 DIPHTHERIA. inhalation [Formula 24]. No operation whatever may be required should the foregoing procedure be happily effected. On the other hand, there may be noticed a redness of the vocal cords without much membrane in the glottis, in which case intubation would relieve the associated spasm ; or such an amount of membrane may be seen on the cords and below them as to contra-indicate intubation and to demand tracheotomy. Other data have to be considered before we can decide whether to intubate or to open the windpipe. From the standpoint of statistics one cannot give preference to one or the other, except that in children under four years intuba- tion is probably a more successful operation. The question is, which is the more simple and more easily executed, and what are the advantages and inconveniences of each ? Even in experienced hands, difSculties often occur in the intro- duction of the intubation tube which inay equal those of tracheotomy. E"ot infrequently it has been found necessary to perform tracheotomy after intubation, because the latter may fail to afford relief to the embarrassed respiration, or it may be found impossible to nourish the child properly ; and the operator should be forearmed against this eventuality, having ready the necessary intruments for an immediate tracheotomy in case the intubation tube cannot be introduced, or if, in the very act of introducing the intubation tube, membrane has been pushed down so as to block the respiratory tract. And the same precaution should be observed when proceeding to withdraw an intubation tube from the larynx, often an even more difficult operation than the introduction, so that it would be well that the instruments for the two operations were always carried in the same case. A point not in favour of intubation is the fact that the removal and re-introduction of the tube requires skilled hands, whereas the nurse may remove, cleanse, and replace the tracheotomy tube. In hospital practice, where everything is ready and skilled assistance at command, there is more to be said in favour of intuba- tion than there is in pri^^ate practice, in which these difficulties LARYNGO-TRACHEAL DIPHTHERIA— CROVP. 193 rather prevent intubation from becoming a formidable rival to tracheotomy. After intubation there is usually, as already premised, trouble in deglutition, but this difficulty may be overcome by giving food of a semi-solid consistence and in a particular manner to be presently described. False membrane and mucus from the trachea is expelled less easily in intubated cases, and the tube is liable to blocking by exudation drawn upwards into it on coughing; but this latter accident is quite as probable in the case of tracheotomy. It is, however, more easily overcome by the simple removal and cleansing of the inner tube, which can be done by the nurse, at the same time clearing the trachea by long forceps or feather. In intuba- tion, removal and re- introduction of the intubator when necessary may be unduly delayed in adoption, since being more intricate it requires technical skill. In almost any case, and especially where there is a large amount of exudation or mucous secretion, the intubation tube may require to be removed at least daily for the purpose of cleaning. The operation of tracheotomy gives functional rest to the larynx, and permits a more thorough clearing away of membrane and more efficient medication of the regions both above and below the tracheal opening. And not the least valuable point in favour of tracheotomy is the access which it gives for the application of solvents such as lactic acid, disinfectants such as biniodide of mercury, or liquefiers of mucus such as bicarbonate of sodium, whereas intubation is actually adverse to employment of these valuable auxiliaries. In view of the tendency of the diphtherial poison to attack peripheral nerve tissue, especially of those muscles which are most in use, and in the order of vital importance, it is probable that the occasional ulcer caused by pressure of the intubator is a direct result of paralysis and degeneration of the laryngeal muscles. In very young children, under four years of age, intubation has given better results than tracheotomy. Stern's statistics show 194 DIPHTHERIA. that tinder three and a half years, intubation gives a decidedly larger number of recoveries. Being a bloodless operation, and not requiring an ansBsthetic, the consent of parents is more easily obtained, and thus children are saved who would otherwise die owing to inability to obtain the parents' consent for tracheotomy. For a similar reason the operation can be performed earlier, before the patient is moribund — as too often happens with tracheotomy. Finally, for the poor in their own homes it is decidedly superior to tracheotomy. The tracheotomy tube requires constant and even skilled attention, whereas the intubation tube in cases suitable for its employment may often be allowed to take care of itself. Tracheotomy. This is a procedure which is each year viewed more favourably, mainly because the indications for its performance are becoming better appreciated, and we are now able to assure the relatives of a patient that, when adopted sufficiently early, the chances of success are much greater than formerly. The indication for operative interference, whether tracheotomy or intubation, is the occurrence of progressive asphyxia as evidenced by the suppression of voice, increasing dyspncsa, stridor, cyanosis, and especially by the retrocession of the chest walls. When on auscultation the vesicular murmur is not clearly heard, but in its place the inspiratory laryngeal sound, there should be no delay in operating, though an attempt should always be made to verify the cause of the symptoms by the physical signs as capable of detection by the laryngoscope. There are, indeed, no contra- indications for tracheotomy once its necessity is indicated, and the sooner it is done before exhaustion sets in and the system is loaded with toxines the greater the chance of success. The younger the child the less should be the delay." Another reason for early operation in laryngo-tracheal diphtheria is its well known tendency to spread downwards, and thus set up a serious membranous bronchitis. . LARYNGO-TRACHEAL DIPHTHERIA— CROUP. 195 In our series of 1000 eases of diphtheria, we find tracheotomy was performed by Dr. Gayton, the medical superintendent, and his assistants, in 68 instances. Of these 34 died and 34 recovered. Of the 34 fatal cases, membrane was present in the larynx alone in 2 ; in the fauces and larynx in 23 ; and in the fauces, larynx, and nares in 9 instances. In the total number of 68 patients on whom tracheotomy was performed : — In 3 cases membrane was present in the larynx. .. 49 „ „ „ fauces and larynx. >, 16 „ ,, „ fauces, larynx and nares. The percentage mortality for site is : — Larynx, . . . . 66-6. Fauces and larynx, . 46'93. Fauces, nares, and larynx, 5 6 '2 3. Total mortality, 50 per cent. In support of the value of tracheotomy. Dr. Gayton points out that since greater reliance has been placed on this procedure the death rate from diphtheria at the North-Western Hospital has been reduced from 3142 to 26'48 per cent., including those very numerous cases which, admitted in a hopeless condition, die within 24 hours. If these were deducted the mortality would be reduced to 22 '6 per cent. Dr. Gayton concludes the valuable paper from which these remarks are taken by saying that " beyond all question many lives may be saved by an early resort to opening the trachea." Especially is this so in that class of case in which the strength is main- tained, but in which the danger is death from asphyxia. As to the risk of pulmonary complications, and, in particular, broncho-pneumonia, to which a useless tracheotomy would expose the patient, we do not think we are justified in making that an argument for delaying tracheotomy to the last moment. Early tracheotomy is, then, more advantageous than late tracheotomy. In other words, one need not wait till there are 196 DIPHTHERIA. pronounced signs of asphyxia, but, on the contrary, should act as soon as there is slight suffocation and dyspnoea. Another advan- tage of this practice is to spare the patient not only hours of anguish, but much emotion and pain. Besides, the early operation not being suddenly called for is carried out under antesthesia, is done without hurry, and in every respect under the best possible conditions. If even before occurrences of respiratory signals of distress membrane can actually be seen in the larynx by means of the mirror, no delay should be allowed to occur, and the 'advisability of opening the windpipe should be promptly urged. We do not advocate its performance where the chances are, from excessive toxaemia or septicEemia, hopelessly unfavourable, because knowledge of fatal results tends to influence parents in their refusal under circumstances which are perhaps most favourable. Nevertheless, it is noted that in many cases in which death occurs after tracheotomy, the operation gives some days or hours of quietness, and the end is much more tranquil than would otherwise have been the case. We must always consider this operation principally with regard to children, in whom death by mechanical obstruction is much more frequent than in adults. In the latter, tracheotomy is far less frequently called for, and it would appear is less successful than in children, probably because the dyspnoea when present is not so purely mechanical in its nature. The scope of this essay does not call for any great details as to the performance of tracheotomy. These are to be found in all surgical text-books. The operation itself, though an easy one in the adult and in chronic disease of the larynx, is, on the other hand, full of difficulty (in so acute a disease as diphtheria), and in the very young, on account not only of the spasm, but of the depth at which the trachea lies in the case of a fat child, the shortness of the neck, the relatively large size of the thyroid isthmus, and, up to the age of about fifteen months, the possible presence of the thymus gland. We may further note that it is well to make the operation as LARYNGO-TRAQHEAL DIPHTHERIA— CROUP. 197 far as possible a bloodless one by discarding the knife after the skin incision is made, and separating the soft parts by means of dissecting forceps. The trachea should not be opened until its rings are clearly exposed and made free of all superposed tissue. We are in favour of a moderately high tracheotomy, and always endeavour to cut below the first and, if possible, the second tracheal ring. A point by no means unimportant is to make a sufficiently long skin incision, and it may be added that all blood vessels should be doubly secured by forceps before dividing them. We are not in accord with those who put in the tube before bleeding has stopped, in the belief that once the tube is introduced haemorrhage will be arrested. That way danger lies. Anaesthesia. — A local anaesthetic, such as cocaine hypodermi- cally employed, may be permissible and even advisable in the case of adults, but for children and for diphtheria we recommend a general antesthetic, however late the stage of the disease ; even in an emergency, when, as has been taught, there is no time for its administration, for the chloroform allaying spasm diminishes the immediate danger. There always is, indeed, less risk of the anaesthetic doing harm than there is from undue spasm, unrest, and constant upheaval where it is not employed. To this rule there is hardly an exception. Chloroform is far preferable to ether, which is, indeed, contra- indicated from its liability to induce rather than to allay spasm of the glottis. The operation over and respiration re-established, a successful result largely depends on careful nursing of the patient, careful cleansing of the tube and dressing of the wound, together with the observance of strict hygienic precautions. The temperature of the room should be kept constant, and the carbolic or other vapour kept playing continually to moisten and sterilise the atmosphere. Caution, however, must here be given lest the spraying be over- done by being too hot and abundant, and thus lead to greater depression and consequently to a greater liability to pneumonia igS DIPHTHERIA. The spray should be small in quantity and cool in temperature. The inhalation facilitates detachment of membrane, and it may be said that in cases where there is only a small quantity of mucus secretion in the trachea more steam is indicated than when the secretion is abundant, this latter condition being rather a favour- able sign. The after-treatment consists in covering the wound under the tube with an antiseptic dressing, such as blue gauze, and the same to be lightly laid over the orifice. We are also in the habit of having a woollen pad with antiseptic gauze-covering laid over the chest to preserve from damp and cold arising from sprays, steam inhalations, &c. Biniodide of mercury (1 in 4000) is sprayed over and around the wound every two hours. Should the tracheal mucus be scanty and tenacious and difficult to expel, an anti- septic alkaline lotion (Formula 14 or 15) may, in the alternate hours, be applied by the atomiser through the canula, thus favouring a moist condition of mucus — not of membrane — and making expectoration more easy. After tracheotomy in favour- able cases there is high temperature for 48 or 72 hours. Cough aids the expulsion of mucus and membrane, and, indeed, it is often of great utility to tickle the trachea by means of a feather charged with dilute lactic acid, thus simultaneously exciting cough and softening and removing membrane. The inner tube should be removed every one or two hours, cleansed, disinfected, and re- introduced. The tracheal opening is to be regarded not only as affording relief to an obstruction in the natural breathway, but also, and most importantly, as a preliminary to adoption of measures for clearing the air-passages of such membranous obstruction, and the practitioner must not neglect continuance of persevering efforts in that direction, and in such local medication as may prevent exudative re-formations ; but failure to always effect this end, as proved by the presence of membrane in the trachea in a fatal case of membranous laryngitis after tracheotomy, must not be regarded as any evidence of the want of due care on the part of LARYNGO-TRACHEAL DIPHTHERIA— CROUP. 199 the surgeon in charge, as has been suggested by an author on this subject. "With regard to removal of the membrane through the tracheal opening, attempts to this end by oral suction either of doctor or parent ought not to be necessary in these advanced days of mechanical aids. One very simple instrument for the purpose is that of a Siegel's exhausting syringe, such as is employed in aural practice, with a strong exhausting soft rubber bag to effect suction and the aural end adapted to the mouth of the tracheotomy tube by means of the aspirator, known as Coudereau's. By this instru- ment, made for us by Messrs. Krohne and Sesemann, not only can exudation be extracted, but by a very simple contrivance, familiar to all who use aspirators, fresh air or hyper-oxygenated air can be introduced into the lungs almpst instantaneously after the extraction. An atmosphere of steam is more necessary after tracheotomy than before, since it is most important to guard against the occurrence of fresh inflammation due to inspiration of insufficiently tempered air by the tube. One other hint hardly necessary to experts. In removing membrane through a tracheal canula, it is better to clear it by the inner tube, so that in case that passage is blocked freedom can be given to respiration through the outer canula. A double canula, always of value in tracheotomy, is of indispensable im- portance in cases of diphtheria. At the end of twenty-four hours, the canula should be removed and replaced by another of the same size and shape, and this pro- cedure should be repeated at least once a day until the tube is finally removed. Before this last step is taken, the tubes should be removed for a gradually increasing period of from four to eight hours. The withdrawal of the canula often occasions expulsion of much membrane and mucus. The constitutional treatment should be continued, namely, iron and chlorate of potash, and the indications for alcohol already given should be diligently observed. The child should not be overfed, a small quantity every two or three hours is sufficiently often, and 200 DIPHTHERIA. it is a point worthy of notice that soft semi-solid food is more easily swallowed than liquid. Feeding by the (Esophageal tube may require to be resorted to. The possible complications after tracheotomy are peri-tracheal cellulitis and abscess, emphysema, erysipelas, membrane on the wound, gangrene, and broncho-pneumonia. The last is by far the most frequent cause of death after tracheotomy, a less frequent cause being cardiac failure, and still less, membranous bronchitis. The other complications are, no doubt, largely due to lack of antiseptic details. According to Cadet de Gassicourt, the cases of broncho-pneumonia which get well are those which appear from five to eight days after the operation, whereas those which follow tracheotomy in one or two days usually terminate fatally. Intubation of the Laeynx. This procedure for relieving laryngeal dyspnoea by introducing a tube through the mouth, and placing it in the larynx with its upper end below the epiglottis, was first adopted by Bouchut in 1858; but the credit of re-introducing and gradually perfecting the instruments and method now in use must be assigned to Dr. Joseph O'Dwyer, of New York, who commenced his experi- ments in intubation in 1880. We have mentioned some objections which render it doubtful whether intubation can ever entirely supersede tracheotomy, but without doubt there are many cases in which it may, at any rate, be adopted as a preliminary, and in not a few as a substitute. The operation has been performed extensively in America and to some extent in this country, and has been successful in very young children, the very class, in fact, in whom tracheotomy has given the least favourable results. We had the opportunity of seeing some cases at Chicago under the care of Dr. Waxham ; we have since had some encouraging experiences of the operation in our own practice, and we are bound to confess that many former LARYNGO-TRACHEAL DIPHTHERIA— CROUP. 201 objections which we entertained have been almost entirely dissipated ; and in a communication read at the meeting of the British Medical Association at Glasgow in 1888, we stated somewhat fully our mature views on the subject, which further experience has confirmed. The vast difference in the frequency with which the operation has hitherto been performed in America and in this country is no doubt partly due to the greater prevalence of diphtheria in America. It is probable, however, that the laryngeal mirror not having been used in the majority of cases, for the purpose of forming an exact diagnosis of the condition of things, the opera- tion may have sometimes been performed for mere spasm, and before membrane had extended to the glottis. In any case, it is unquestionable that some of those who have had the largest number of cases of intubation in America are not laryngologists, nor expert with the laryngoscope. On the other hand, a large number of cases have been recorded by Eoe, Ingalls, Casselbury, Stern, and Bleyer, to the nature of whose cases such an objection could not possibly be advanced. A set of intubation instruments as now generally sold consists of five laryngeal tubes, together with a gag, an introducer, and an extractor. A scale is also supplied indicating the length of the tube suitable for a particular age. The tubes are made of brass plated with gold, and vary in length from If to 2| inches. The calibre of the largest tube is about ^ by \ inch, and that of the smallest about half that size. The upper end of the tube is expanded into a head, which rests on the ventricular bands and prevents the tube slipping down into the trachea. The anterior part of the head is levelled oif so as not to press on the base of the epiglottis. There is a small hole near the anterior part through which a thread can be passed. In the middle of its length is a fusiform enlargement by which the tube is retained in the larynx. Each tube is supplied with a so-called obturator which is inserted into the tube, and fits the openings accurately at each end. In the upper end of the obturator is a small hole by which it can 202 DIPHTHERIA. be screwed on to the introducer when the tube is about to be used At the distal end the obturator projects slightly so as to form a probe-pointed extremity, which diminishes the risk of injuring the parts during introduction. The introducer consists of a handle and a shank, bent at its distal end at a right angle. To this end the obturator is screwed on, and, by pressing a button in the iipper surface of the -handle, two claws may be made to project down- FIG I Pig. 61. — Intubation Instbuments. wards on the head of the tube, so as to push it clear of the obturator, and to allow the introducer with the attached obturator to be .withdrawn when the tube is in position. The extractor is a curved instrument, at the distal extremity of which two small blades can be made to dilate by pressure on a spring in the handle. The extremity is inserted into the tube with the blades closed. LARYNGO-TRACHEAL DIPHTHERIA— CROUP. 203 when pressure on the spring causes the blades to open, and the tube to be firmly held. In perfm-miTig intubation the first step is to select a tube suitable to the age of the child, which may be done approximately by reference to the scale. The tube is threaded with a piece of braided silk some sixteen inches long, the ends of which are tied together. The obturator is then screwed on to the introducer, and the tube is fitted on to the obturator. The nurse, seated upright in a straight-backed chair, takes the child in her lap with its back pressed against the left side of her chest, and its head thrown slightly backwards, resting against her left shoulder. She passes her arms round the child, and crosses its forearms in front and holds the wrists tightly, and if necessary she secures the child's Pig. 62. legs between her knees. The gag is next placed well back at the left corner of the mouth, and an assistant, standing behind the nurse's shoulder, holds the gag and steadies the head between his hands. The following are the directions usually given : — The operator, standing or sitting in front of the child, takes the introducer in his right hand and hooks the loop of thread round the little finger of the left hand. He then rapidly passes the index finger of the left hand over the tongue and behind the epiglottis till the upper orifice of the larynx is felt. With the handle of the introducer held close to the patient's chest, the tube is introduced into the mouth and passed back over the base of the 204 DIPHTHERIA. tongue, guided by the index finger, and kept as nearly in the middle line as possible. When the point of the tube reaches the epiglottis, an abrupt turn is given to its course by raising the handle of the introducer, and thus bringing the tube into a vertical position. The tip is then passed into the larynx along the palmar surface of the guiding finger. As soon as the tube is in the larynx it is detached from the guide by pressing forwards the button on the handle, and as the guide with the attached obturator are withdrawn, the tube is pressed down with the tip of the left index finger until its flange is felt to rest on the ventricular bands, when the finger is at once withdrawn. Fig. 62, which is taken from Dr. Waxham's book, represents the curve that should be made by the end of the tube while it is being introduced, the dark line indicating the path it should follow. If the point of the tube be continued in the curve as indicated by the dotted line, it will invariably enter the oesophagus. The entry of the tube into the larynx is indicated Ijy violent coughing, quickly followed by easy breathing. We have been astonished by the rapidity with which the bases of the lungs are aerated, and if there is any doubt as to the position of the tube the surgeon's ear applied to the back of the little patient will often settle it. If the instrument has passed into the 03sophagus there is no violent coughing, and no relief is given to the breathing, and the loop of thread will be found gradually shortening as the tube sinks into the oesophagus. In that case the loop should be pulled upon, and the tube withdrawn. When quite satisfied that the tube is in the larynx, the operator removes the gag and waits a few minutes to allow the cough to remove the mucus and fragments of softened membrane. It is recommended that the gag should be then replaced, and the loop cut close to the mouth, and while the left index finger is passed down on the head of the tube to steady it, the thread should be drawn out, but in many cases it is better to leave the thread in for a short time, fastening it to one or other cheek by a small strip of plaster. LARYNGO-TKACHEAL DIPHTHERIA— CROUP. 205 When the tube has to be extracted, the patient is placed in the same position as for introduction. The gag is inserted, and the left index finger is passed behind the epiglottis till it feels the opening in the h^ad of the tube. The extractor, in the right hand, is introduced, and its point guided into the opening by the finger. By pressing on the lever in the handle the blades are dilated, thus holding the tube firmly while it is withdrawn. Intubation is an easy and safe operation in the hands of an operator -possessed of moderate dexterity and a thoroughly practi- cal acquaintance with the parts dealt with, but to one not accustomed to put his finger in this part of the throat, the first attempt will often be attended with difficulty or failure. As we have remarked in the paper already referred to, it is in a sense a tribute to the merit of intubation that the most successful results have hitherto been obtained by practitioners, not laryngeal specialists. With the gag in the mouth it is perfectly possible to see the glottis with the laryngoscope, especially with the aid of Dr. Bleyer's traction-hook, which exposes the epiglottis, and it is not only more easy and rational, but obviously far more safe, to introduce the tube by means of the eye than by the sense of touch, especially as by the introduction of the hand there is great risk of increased suffocation as well as of injury to the soft parts in a condition of inflammation or ulceration. Moreover, to learn the knack of introducing an instrument by sight requires no more practice than the guiding of it by the sole aid of the finger, and the- same may be said as to its extraction. After the tube has been placed in the larynx, and after the first effects of irritation have passed off, respiration will usually be carried on easily. It has occasionally happened that during the introduction false membranes have been detached and pushed down before the tube, thus causing suffocation. The accident is rare, and when it has happened immediate removal of the tube has almost invariably been followed by coughing up of the mem- brane. Should this not occur, tracheotomy should be done, and it is therefore well to have tracheotomy instruments ready at hand. 206 DIPHTHERIA. During the course of the treatment the tube is cleared of mucus by the ordinary efforts of respiration and cough. If it become clogged it is usually coughed up. There is, as a rule, no danger of suffocation in such cases for some hours, so that ample time is usually allowed to summon the physician or surgeon in charge. Sometimes the tube is coughed up independently of getting blocked. When the tube is very easily coughed up, it is an indication that the size used is too small. It is usually ejected from the mouth, but it has occasionally been swallowed, and in all the recorded cases where this has happened (with one exception, when it was found post-mortem no further down than the stomach), it has been passed without difficulty per rectum. The tube must be extracted at any period of the treatment if there are symptoms of its being obstructed. Otherwise, most operators do not interfere with it. In the course of from four to six days the swelling and spasm will have so far diminished that the tube will be coughed up, and it will then probably be found that it is no longer required. If about the sixth day it be not coughed up, it should be removed with the extractor and need not again be introduced if the breathing is easy. Some children after intubation swallow without difficulty both liquids and solids. In others, each attempt to swallow, more especially liquids, excites cough, owiiig to the entry of some portion into the air-passages. Semi-solid food is therefore pre- ferable. It is, however, usually possible to overcome the difficulty of swallowing, even of liquids, by placing the child on its back in a horizontal position with its head hanging backwards, as described by Casselbury. In this position the child may suck from a bottle or be fed with a spoon. In some cases the child swallows as well or better lying on the abdomen with the head hanging forwards— that is, in the same position as that found to be convenient in cases of dysphagia due to tuberculous ulceration of the epiglottis. CHAPTEE XII. HYGIENE AND PROPHYLAXIS OF DIPHTHEEIA. The preventive measures to be observed with regard to diphtheria differ in no great respect from what would be re- quired in the case of any other infectious or contagious disease. They pertain not only to the patient and his surroundings, but also to the nurses and others in attendance during the attack, with a view to the prevention of the conveyance of the contagium from the sick-room to others. Secondly, to the disinfection of the sick-room, furniture, toys, clothing, &c., and to the correction of all sanitary defects which may be in any degree responsible for an outbreak, and lastly to systematic measures of prophylaxis in schools and school-houses. As to the surroundings, every opportunity must be embraced of purifying the air of the sick-room and purging it of noxious ex- halations ; this purpose is best effected by securing to the patient an atmosphere well charged with oxygen. Every precaution must be taken against a further development of the poison as con- veyed in the defsecations and eliminations of the tainted in- dividual. All excretions should be treated with strong liquid disinfectants, and the w.-c. employed for their bestowal should not be used even by the immediate attendants, — in fact, in this respect every precaution should be observed as would be enforced were the case one of enteric fever. Since disinfection of the atmosphere by chlorine, euchlorine, iodine, bromine, sulphurous acid, or any of the other more active but somewhat suffocative disinfectants is not generally feasible in the patient's room or immediate neighbourhood, the atmosphere 2o8 DIPHTHERIA. passing to and fro the doors and passages of the sick-room may be asepticised by sheets soaked in Burnett's fluid, sanitas, eucalyptus, and similar solutions. A " Sanitas " kettle may be conveniently placed outside the room over a Bunsen gas burner, so that when the door is opened the air comes in not only warm and moist, but impregnated with oxidising constituents. Sprays of Condy's fluid, Sanitas, &c., by means of hand-ball or steam atomisers may also be employed in the room. Nothing should be allowed to go from the sick-room unless pre- viously treated with disinfectants. All utensils — plates, cups, forks, spoons, &c. — used by the patient must be immediately disinfected by being washed in some germicide solution, such as perchloride or biniodide of mercury. In cases where the water supply is suspected as a source of infection, all water used for the patient and household should have been previously boiled ; the same precaution should be observed with regard to milk, whether 'or not its purity be under suspicion. Old linen rags are preferable to the ordinary pocket-handker- chiefs, as they can be burnt after use ; and every dressing, poultice, &c., should be immediately committed to the fire, which for purposes of preparation of food, &c., should always be kept burn- ing in an adjoining chamber if the season of the year does not require it in the sick-room. Articles of clothing, bed-linen, &c., should be placed in a suitable receptacle containing a solution of 1 in 2000 perchloride of mercury, or 1 in 4000 biniodide of mercury, before being removed from the chamber occupied by the patient. The nurses and attendants should wear blouses which can be removed on their leaving the patient, and the medical attendant would also do well to wear a similar protective dress before entering the patient's room. Scrupulous attention must be observed in well washing the hands, brushing the finger-nails, &c., with dis- infectant solutions after every visit to the patient, and the physician would be acting wisely in refraining from visiting any young children for a few hours after attending a case HYGIENE AND PROPHYLAXIS. 209 of diphtheria, and even then only after a complete change of clothing. Sufficient insistance has been made on the all-important con- firmation by bacteriological examination of the clinical diagnosis of diphtheria directly a case comes under observation. It is also equally important that by the same means the thorough recovery of each individual attacked should be accurately determined. "We have already remarked that the aerial communication of diph- theria from bed to bed in hospitals is in all probability of rare occurrence ; but we are not at all so sure that there is equal immunity in regard to the infectiousness of such septic conveyance as may be due to the association of diphtheria bacillus with coccal organisms ; and Moizard has urged that in hospitals where diphtheria is treated, every patient suffering from broncho- pneumonia, or other complication of a septic nature, should be isolated as a routine measure. This course of action might, however, be somewhat difficult to carry out in ordinary practice, and its mere suggestion may per- haps be regarded as an undue refinement of prophylaxis ; but it is by no means as fanciful as may at first sight appear. For we have noted in quite a considerable number of our cases in which the first bacteriological examination has proved the diphtheria bacillus to have been associated only with single cocci or diplo- cocci, that a second examination similarly conducted in the con- valescent stage has — while declaring the bacillus diphtherise to be absent — noted the appearance of other organisms of greater im- portance than those originally present, especially streptococci. These bacteriological examinations of convalescent patients are of the more importance, because in diphtheria no clinical criteria exist of complete recovery similar to those evident in scarlet fever, smallpox, chicken-pox, whooping cough, measles, and the like. The length of period that the bacilli of diphtheria may remain in the throat in a state of virulence varies very considerably. Loeffler and Park maintained it in an active state for seven months on blood-serum. Eoux and Yersin found the bacillus in 210 DIPHTHERIA. dried shreds of membrane in a condition of virulence after twenty weeks ; and Morell Mackenzie has related several eases, which occurred in pre-bacteriological times, proving that the appearance of sporadic cases of diphtheria could only be accounted for by an equal or even longer period of vitality of the bacillus. The following statistics made by Park and Beebe are of in- terest .: — Out of a total number of 605 cases of diphtheria which recovered, these observers found that in 304 the bacillus disappeared within three days after the disappearance of the exudate; in 176 cases the bacilli remained for 7 days ; in 64 eases, for 12 days ; in 36 cases, for 15 days; in 12 cases, for 21 days; in 4 cases, for 28 days ; in 4 cases, for 35 days ; and in 2 cases, for 63 days after the disappearance of the membrane. In all of these cases the specific microbes, although growing gradually less numerous and becoming more admixed with cocci, were still virulent, and generally to the date of their final disappearance. In the foregoing pages we have reported how bacilli in a state of attenuation were found to be present on a wound after tonsillotomy, three months after the patient's discharge froin the hospital {Case. 4). We have also followed the history of another case in which diphtheria bacilli in full activity and virulence were found 80 days after the patient's throat was clear of all exudation. And a third case has been recorded {Case 13), in which the patient engaged officially in the diphtheria wards of an Infectious Fever Hospital, had four attacks of the disease in a period of three years. Never- theless, examination on the 24th day after the fourth attack failed to detect the presence of any bacilli of diphtheria in the patient's throat. And yet again, we have mentioned an instance of croup (page 183) in which there was never any but the slightest sign of exudation — and that only in the larynx. Bacilli, however, were found in the secretion from the throat upwards of a month after intubation had been performed, the only sequel* being slight loss of reflexes. HYGIENE AND PROPHYLAXIS. 211 In view of the existence of these elements of uncertainty, it would appear to be impossible to exercise too much caution in respect of definite confirmation of complete recovery. The throat of every patient recovering from diphtheria should be syringed, and treated with antiseptic gargles and solutions. Bacteriological examinations should be regularly made once a week, until they fail to detect the presence of the specific bacillus. Moreover, in regard to what has been said of the presence of the bacilli in the throats of those attending on diphtheria patients, the same precautionary measures of gargling and bacteriological examination against the conveyance of infection to susceptible persons should be strictly enforced ; for we have knowledge of the fact of diphtheria occurring three times in the daughter of a medical superintendent of a fever hospital (the lady in question never having visited the wards). Her first attack came when she was three years of age and the last when she was nineteen. In the event of fatal termination to a case, it is most advisable that relatives not previously in attendance should abstain from even visiting the sick-room, much less run risk of contagion by kissing the deceased. This precaution is to be specially observed with regard to young children. Doctors and nurses each time after being in close contact with a patient might observe a hint which we have adopted from the practice of a sanitary engineer, who, whenever he, was obliged to inhale any unpleasant effluvium, blew his nose freely, gathered his saliva, and expectorated. A recent editorial article in the Lancet has well said that " the prevention of the spread of diphtheria through the agency of schools is certainly one of the most difficult duties which devolve upon the medical officer of health. On the one hand he is prompted to school closure or the exclusion from school of children from infected localities or houses ; and on the other, he is anxious, as far as possible, not to interfere unduly with the educational work of the institution and the prospect of the Government grant." 212 DIPHTHERIA. We have already given our reasons for the opinion that the mode in which diphtheria is disseminated by what has come to be called " school influence " has been generally misunderstood, and have endeavoured to show that the disease does not originate in the school, but that it is usually introduced from the home, to be afterwards very likely transmitted and disseminated to other homes from the school. Many medical officers of health are commencing to realise this fact, and several have recently instituted a systematised examination of the throats of all children on the re-assembling of schools, relegating those who appear at all affected to their homes for treatment and exclusion; and for the inspection and remedy of any sanitary defects apparent therein. This last is essential in any case, and whenever operative measures, such as the removal of tonsils, faucial or pharyngeal, are indicated, it is desirable to insure that there is no diphtheria or other infectious disease existing in other members of the same household. Where these precautionary measures of examination have been systematically adopted a remarkable diminution of diphtheria and other infectious diseases has been noticed in districts where they have long previously been endemic, and as a consequence school closure and interference with regular education is becoming less frequent. But we would urge that something more should be done. We have seen that a considerable proportion of outbreaks of diphtheria has been preceded by attacks, not only of enteric and scarlet fever, but of other non-notifiable diseases, such as measles and simple sore throat. To these might be added chicken-pox, German measles, and whooping-cough, which are known to increase the gravity of an attack of diphtheria to such an extent, indeed, as to merit statistical notice in the Annual Eeports of the Asylums' Board for the current year. Parish councils, school boards, and other ruling bodies under the growing influence of extended local government should recognise their responsibility in the matter of other diseases, than those HYGIENE AND PROPHYLAXIS. 213 included under the Notilication Act, capable of being fostered in school buildings and others where many persons are coiagregated, and should make arrangements for the periodical inspection of all schools by responsible medical practitioners, preferably the medical officer of health. Indeed, such an- officer ought 'to -be attached to all these bodies, and we are convinced, from the present high qualifications required from public health officers, that their presence on all committees relating to the erection of new buildings and the maintenance of good sanitation would be attended with results of far-reaching value and of true economy. Throat examination. — For this purpose it is necessary to have a metal tongue depressor, a laryngeal mirror, and a nasal speculi^m ; a separate tongue cloth should be used for each child and immediately burnt. The attendant should, after each exami- nation, disinfect all the instruments in some strong antiseptic solution, at high temperature, of either lysol, eresol, or biniodide of mercury. In all cases in which the patients have contracted the habit of mouth-breathing, measures operative or otherwise should be adopted to reduce to a minimum the chances of recurrence of an attack of diphtheria, and the same should be adopted in other members of the family, and, indeed, of all children who are thus possessed in a high degree ■ of receptivity to diphtheria and associated infectious diseases of the throat. Preventive surgical treatment. — This is not the place to describe methods of operation, but a hint or two may be here given as to the removal of the tonsils, both faucial and pharyn- geal. (1.) When the faucial tonsils are unequally enlarged, it is well to remove both, for, as in the case of tonsillitis, the inflam- mation having been reduced on one side is very apt to pass to the other, so if one tonsil only be removed the other is very liable to become hypertrophied. (2.) In all children under puberty, and in some adults in whom 214 DIPHTHERIA. the tonsils are large, there is almost always similar overgrowth of the pharyngeal tonsil. It is not necessary to put a child to the somewhat terrifying procedure of exploration with the finger behind the soft palate for diagnostic purposes prior to operation, but the vault should always be examined and, if necessary, cleared as a logical complement of a faucial tonsillotomy. (3.) Cases undoubtedly exist in which the pharyngeal tonsil is enlarged without overgrowth of the faucial. In these cases there is generally some thickening of the faucial pillars, indicating chronic inflammation. By closing first one and then the other of the nostrils by the finger and causing the patient to breathe on to the hand of the examiner, a good idea of the amount of obstruction to nasal respiration can be obtained. In cases where there is reflex laryngeal cough, nasal catarrh, and liability to head cold, &c., one may with certainty predicate adenoid vegetations, and this even in cases in which there may be also evidences of a specific dyscrasia. (4.) In almost all cases of nasal and faucial stenosis there is paresis of the soft palate with relaxation of the uvula, but we make it a rule, to which there is hardly an exception, not to remove any portion of the uvula of a child under the age of puberty at the same time that we perform faucial tonsillotomy or naso-pharyngeal curetting ; having found in almost all eases that muscular tone will quickly be regained when once free nasal respiration is restored. (5.) In like manner there is some turgidity of the turbinal bodies in cases of nasal stenosis, which has been called hyper- trophic rhinitis, but this term is clearly a misnomer when applied to young children ; for one cannot talk of an overgrowth of tissues which are not fully developed until puberty, as is the case with the turbinals. On this account we rarely treat the turbinal congestion by any active means, finding that it also almost always disappears so soon as congestion is relieved by removal of adenoids and the re-establishment of nasal respiration. HYGIENE AND PROPHYLAXIS. 215 (6.) We do not advise the use of the nasal syringe in the chronic catarrhs of young children, since, as Bosworth says, the parts are already " waterlogged " by a hyper-secretion of moisture. In these circumstances nasal douches are but too likely to induce a life-long nasal catarrh. In any case we never syringe more than two ounces of a solution into each nostril on any one occasion, whether the patient be child or adult. Disinfection of the sick-room after the termination of a case of diphtheria. — Disinfection in private residences is generally carried out by officials in the employ of the sanitary authorities of the particular district in which the patient resides. All bedding, pillows, blankets, mattresses, carpets, curtains, &c., are effectually disinfected by treatment with super-heated steam, for which purpose they are sent to the nearest disinfecting station. The proper disinfection of the sick-room, however, offers more difficulty. Having knowledge of many instances in which the official course of disinfection has proved to be inadequate, a brief outline of the necessary steps which should be taken to speedily and effectively disinfect a room or rooms in which diphtheria cases have been treated will not be considered superfluous. Among the many methods of disinfection the burning of sulphur with the production of sulphurous acid is perhaps the most common and the most efficacious when properly carried out. It is necessary for perfect disinfection that the room should be as far as possible hermetically closed ; the windows tightly shut, the register of the fire place pulled down, and every outlet, chink, and crevice blocked up. One pound of sulphur — preferably in the convenient form now supplied under the name of "sulphur candles" — should be pro- vided for every 1000 cubic feet of air space to be disinfected. It is particularly to be noted that to produce the most effectual results from sulphur combustion an adequate supply of moisture must be present. For this purpose, the vessel in which the sulphur is burnt may with great advantage be placed in a large flat pan 2i6 DIPHTHERIA. filled with steaming water; and similar pans of water should be placed in other parts of the room which is to be disinfected. The combustion of the sulphur results in the production of the dioxide ; this gas in the presence of aqueous vapour becomes sulphurous and subsequently sulphuric acid. It is on these chemical changes that the powerful disinfectant action of sulphur in a state of combustion depends. Other oxidising agents, such as ozone, produced by the action of sulphuric acid on permanganate of potash ; nascent chlorine, generated by the action of sulphuric acid on a mixture of common salt (chloride of sodium), and dioxide of manganese, or by hydro- chloric acid on bleaching powder (chloride of lime), may be em- ployed for disinfecting purposes. The room should be kept closed for eight to twelve hours after any of these procedures. At the expiration of that period all the windows and doors must be opened, and kept open for twenty- four hours. Further, it is necessary for complete success that the wall papers should be stripped ; the ceiling redistempered or painted ; the floor, woodwork, and indeed the whole room thoroughly washed with soap and water, followed by a further cleansing with either a solution of 1 in 2000 of perchloride of mercury, or of 1 in 20 of carbolic acid. Unless some such means are adopted after a case of diphtheria occurring in a private residence, pro- phylaxis against further infection cannot be considered to have been pursued to complete efficiency. Finally all defects in sanitary surroundings which might be reasonably held to be responsible for an illness or outbreak should be rigorously searched for, and when found should be immedi- ately and thoroughly corrected. CHAPTEE XIII. FOEMUL^. FOR REMEDIES IN DIPHTHERIA. The following short list of prescriptions of the remedies useful in the treatment of diphtheria and its associates is for the most part limited to those mentioned in the text, and is by no means held to be in any degree exhaustive. To prolong it would, however, only lead to confusion. The dosage of the mixtures is — unless otherwise stated — arranged, as in the Pharmacopoeia of The Central London Throat, Nose, and Ear Hospital, on the plan of prescribing the amount for an adult dose as half-an-ounce. The quantity to be administered to patients of varying ages is, therefore, easily calculated, and may be indicated on the prescription by ordering the dose as 1, 2, 3, or 4 teaspoonsful, as required. In some instances it may be desirable to dilute these doses with an equal quantity of water. The interval between each separate dose should be from four to six hours. In the case of a disease such as diphtheria, which for the most part attacks young children, some variation in the doses will be required to be made for differences of even a year or two in the patients' ages, and also according to the personal equation of vital and assimilative power in each individual instance. To these prescriptions for medicinal remedies there will be added some formulae for preparing staining solutions for micro- scopical examinations, and a few directions as to beverages and articles of diet, which may be found useful by the young practi- tioner. It will be observed that there are no prescriptions given for 2i8 DIPHTHERIA. Gargles, but all the Lotions can be used for that purpose. Con- sidering the tender age of most of the subjects of diphtheria gargling of any kind is almost impossible, and even with those old enough to understand, as pointed out in our chapter on treatment, the procedure is liable, by putting the faucial and palatal muscles into undue and irregular action, to favour the occurrence and severity of palatal paresis. It is, therefore, better that the lotions should be used as mouth washes, or as irrigations with the special syringe recommended (page 171). When gargles are used the method of Von Troeltsch should be pursued. This consists in taking the necessary quantity into the mouth, closing the nose with finger and thumb, throwing back the head and making repeatedly the half act of swallowing ; the pro- cedure requires, however, some amount of intelligence to perform efficiently, otherwise the accident may occur of swallowing the solution, or of letting it into the wind-pipe. It is for this reason we do not recommend gargles to be composed of ingredients of a character likely to prove at all harmful to the general system. No attempt has been made to render any of these prescriptions " elegant,'' the agreeableness of a medium being a question which may well be left to the experience of each practitioner. There is, however, one exception. We have expressed a preference for mouth washes composed of mercuric biniodide over those of the perchloride for reasons of efficacy ; probably from their lessened tendency to coagulate albumen they are also more palatable ; nevertheless, the mineral flavour is to many a drawback to the use of either. This we have found may be greatly diminished, if not entirely overcome, by their administration in a medium of strong Elder flower water, and a form for such a prescription is therefo;?e given. FORMULM FOR REMEDIES. 219 Mixtures. (1) Mistura Sodii Salicylatis Composita. R Salicylate of sodium, Chlorate of sodium, Spirit of chloroform. Decoction of cinchona. 8 grs. 6 „ 10 m. to \ fluid ounce. Mix. (2) Mistura Ferri perchloridi. R Solution of perchloride of iron, Chlorate of sodium, Glycerine, Chloroform water. 20 m. 8 grs. idr. to \ fl. oz. Mix. (3) Mistura Hydrargyri Biniodidi. R Solution of perchloride of mercury (P. B.), 1 dr. Iodide of sodium or potassium, . 4 grs. Peppermint water, to \ fl. oz. Mix. Adult dose, \ oz. For children, 1 dr. (4) Mistura Ferri cum Strychnind. R The same mixture as No. 2, with the addition of the solution of strychnia (P. B.) 3 m. to 5 m. for each dose. The smaller amount can be taken by children up to five or seven years old. (5) Mistura Diuretica. (Kidney Mixture.) R Solution of perchloride of iron, . 20 m. Solution of acetate of ammonium, . 80 m. Chloroform water, . . to ^ fl. oz. Mix. 220 DIPHTHERIA. (6) Mistura Antispasmodica. (Croup Mixture.) R Bicarbonate of soda, . . 15 grs. Wine of ipecacuanha, 5 m. Syrup of chloral . 5 m. Water, . . to 2 drs. Mix. This is the dose for a child five years old or above. For children under five, the dose may require to be modified to half, or less than half, the quantity. (7) Potus Diureticus. YjL Solution of the perchloride of iron is added to lemonade or barley water (sweetened), in the proportion of 5 drops of the iron solution to every ounce of the drink. Children may take nearly a quart of this in 24 hours — representing over 3 fluid drachms of the iron — with no other than a beneficial effect. (8) Oonfectio Potassii Chloratis. R Chlorate of potassium, . . 10 grs. Honey, . 1 oz. Mix. One teaspoonful every 2 or 3 hours, for young children. Topical Eemedies. (9) Pigmentum Acidi Lactici. 1^ Lactic acid (P. B.) For application once or twice a day by the medical practitioner. (10) Pigmentum Acidi Lactici diluti. B^ Lactic acid (P. B.), . .1 part. Distilled water, . . 3 parts. Mix. For application by the nurse or attendant every 3 or 4 hours. N.B. — This may be employed as a laryngeal or nasal application by the medical practitioner, either by means of a brush or as a spray to the affected parts. FORMULM FOR REMEDIES. 221 (11) Pigmentum Ferri perchloridi. 1^ Perchloride of iron, . 1 part. Distilled water, . . .4 parts. For application by brush or swab. Dissolve. (12) Pigmentum Menthol. B^ Menthol, . . 1 part. Oil of sweet almonds, . . 5 parts. Dissolve. For application along the floor of the nostrils by brush or cotton wool swab. (13) Nebula Menthol. Ji Menthol, . 10 grs. Oil of sweet almonds, to 1 fl. oz. To be employed by spray to nose, throat, or larynx. (14) Lotio Alkalina Antiseptica. (Dobell.) I^ Borax, 2 drs. Bicarbonate of sodium, . 2 drs. Glycerine of carbolic acid, 4 drs. Distilled water, to 10 oz. Mix and dissolve. This excellent cleansing and antiseptic solution is prescribed in double strength, and should be diluted with an equal quantity of hot water to bring it to the proper strength and temperature. It may be employed by the syringe or by means of a Lefferts' coarse spray. (15) Lotio Alkalina. IJ: Chlorate of potassium, \ oz. Bicarbonate of sodium, \ „ Borax, . \ „ White sugar (in powder), 1 „ Mix. A teaspoonful dissolved in 5 or 10 ounces of water at 95° F. to be used as a gargle or mouth wash with irrigator, or as lotion to the nose with the nasal syringe. 222 DIPHTHERIA. (16) Lotio Hydrargyri Perchloridi. 5; Perchloride of mercury, . Water, (This solution is equal to 1 in 2000.) For application by swab or irrigating syringe. 1 fl. oz. Dissolve. (17) Lotio Hydrargyri Biniodidi. R Eed iodide of mercury. Iodide of sodium. Water, igr- igr. 1 fl. oz. Dissolve. (This solution is equal to 1 in 2000 of the biniodide.) To be applied as above. (17 bis) Lotio Hydrargyri Biniodidi Odorata. Ti Eed iodide of mercury, 2 grs. Iodide of sodium, 4 grs. Elder flower water (concentrated 1-3), 5 viii. To be used as a gargle, mouth wash, or for oral irrigation. One part of this lotion to three of water makes a solution of the strength of 1 in 6000. (18) Lotio Ohlori. R Chlorate of potash, Hydrochloric acid pure, Water, 30 grs. 30 m. to 10 oz. Dissolve the chlorate of potash in the water, and gradually add the acid. This lotion should be kept in a stoppered bottle, and should be made fresh every day. FORMULA FOR REMEDIES. 223 (19) Lotio Acidi Carbolici. R Glycerine of .carbolic acid (P. B.). For use, mix in the proportion of a teaspooiiful to half-a-tumbler of tepid water. Eecommended as a mouth wash or gargle in cases of pseudo- diphtheria, especially where there is much muco-salivary secre- tions (as in tonsillitis). (20) Lotio Acidi Borici. IJ; Boracic acid, . 1 part. Water at temperature of 100° F., 25 parts. Dissolve. For oral irrigation and also for syringing the external auditory meatus in cases of suppurative otitis. (21) Loeifler's Solution. ^ Alcohol, . 64 parts. Toluol, . 36 parts. Creolin or metacresol, 1 or 3 parts. Menthol, . 10 parts. Mix. For local application by brush or swab in diphtheria, but probably better in pseudo-diphtheria. 22. Unguentum Antisepticum. R Hydrochlorate of cocaine, . 30 grs. Boracic acid, 1 Salicylate of sodium, / of each 40 grs. Creolin, . 2 fl. drs. Eucalyptus oil, . 10 m. Vaseline, to 1 oz. Mix. For application to the nostrils. 224 DIPHTHERIA. (23) Vapor Pini Sylvestris. (C. T. H.) B FiFwood oil, . . . 40 m. Light carbonajbe of magnesium, 20 grs. Water, . . to 1 oz. Mix. One fluid drachm in a pint of water at 140° P. for each in- halation, either by special inhaler or in steam-kettle. (24) Vapor Benzoini cum Chloroformo. R Compound tincture of benzoin, . . 1 fl. oz. Chloroform, . .8 m. Mix. A teaspoonful in a pint of hot water at 140° to 150° F. for each inhalation, or as in the foregoing. Staining Solutions for Microscopic Preparations. (25) Loeffler's Solution. (Squire.) R Concentrated alcoholic solution of methylene blue, . . .30 parts. Solution of caustic potash (1 in 10,000 of water), . .100 parts. Mix. Place coverglasses in this solution for three to five minutes, wash, dehydrate, clear, and mount in balsam. (26) Roux's Double Stain. R Dahlia or gentian violet, . . ,0-5 grm. Methyl green, . . 05 grm. Distilled water, . . . 200 c. e. Mix and filter before use. Sections are placed in this stain for twelve hours, then washed, dehydrated, cleared, and mounted. FORMUl^E FOU REMEDIES. 225 (27) Gram's Method. (Squire.) Place section in the following solution : — Aniline water, . . . .100 parts. Concentrated solution of gentian violet, 11 „ Absolute alcohol, . . . 10 „ for one to three minutes. Einse in absolute alcohol, and transfer to Gram's solution : — Iodine, . . .1 part. Iodide of potash, . . 2 „ Distilled water, .... 300 until they acquire a brown colour ; this takes place in about one to three minutes. The sections are then washed in 90 per cent, alcohol, until they are a pale yellow colour, dehydrated, cleared and mounted in balsam. Articles of Diet. Beef Tea. — Take one pound of beef without fat or bone, mince and bruise the meat with pestle and mortar; place it in a jar containing a pint of cold water ; set the jar in a sauce-pan of hot water and allow to simmer four hours. N.B. — This, as well as other meat, broths, and milk, may require to be peptonised. The following directions are given by Sir William Eoberts for the preparation of peptonised nutriment : — Peptonised Beef Tea. — A pound of finely-minced lean beef is mixed with a pint of water, and ten grains of bicarbonate of sodium added. The mixture is then simmered for an hour and a half in a covered saucepan. The resulting beef-tea is decanted off into a covered jug. The undissolved beef residue is then beaten up with a spoon into a paste, and added to the beef-tea in the covered jug. When the mixture has cooled down to about p 226 DIPHTHERIA. 140° F. (or when it is cool enough to be tolerated in the mouth), a tablespoonful of liquor pancreaticus (Benger) is added, and the whole well stirred together. The covered jug is then kept warm for two hours under a " cosey " and agitated occasionally. At the end of this time the contents of the jug are boiled briskly for two or three miuutes and finally strained. When seasoned with salt it is scarcely distinguishable from ordinary beef-tea. Peptonised Milk. — A pint of milk is diluted with a quarter of a pint of water, and heated to 140° F. Two teaspoonsful of liquor pancreaticus (Benger), and ten grains of bicarbonate of sodium are then added to the warm milk. The mixture is poured into a covered jug, which is placed in a warm situation for one or one and a half hours, and then boiled for two or three minutes. It can then be used like fresh milk. Lemonade. — Pare the rind of three lemons as thin as possible, add one quart of boiling water and a quarter of an ounce of isinglass. Let them stand till next day covered, then squeeze the juice of eight lemons upon half a pound of lump sugar ; when the sugar is dissolved, pour the lemon and water upon it, mix all well together, strain it, and it is ready for use. Barley Water.— To a tablespoonful of pearl barley in cold water add two or three lumps of sugar, the rind of one lemon, and the juice of half a lemon. On these pour a quart of boiling water, and let it stand in lidded vessel and covered with baize or " cosey " for seven or eight hours ; strain it. The barley should never be used a second time. Half an ounce of isinglass may be boiled in the water. APPENDIX. THE SERUM TREATMENT OF DIPHTHERIA. APPENDIX. THE SEKUM TREATMENT OF DIPHTHERIA. PEEFATORY NOTE. The reasons for considering bhis subject as an appendix hardly need detailed explanation. Serum treatment is said to be still on its trial, and on this account as well as in view of the facts to be recorded, we do not feel justified in giving it a position as an integral portion of our therapeatic resource alongside of the older, well tried, and well established methods of the classical treatment of diphtheria. We must all cordially agree with Professor Virchow's opinion that the brute force of the figures which have been displayed as representing a mar- vellous diminution in mortality not only 'in one, but in many centres of observation, cannot but compel all humane physicians to give the so-called antitoxin treatment an impartial trial. On the other hand, many — and we are of that number — must sympathise with the modified ardour of Professor Bergmann, who, reported as still suffering from the scars left by the Tuberculin conflagra- tion, has deprecated acceptance of the serum treatment of diphtheria with that almost blind enthusiasm which was accorded to Koch's remedy on the high reputation of its author. We well remember the caution that Professor Syme used to give his students, that it was easy to discover any sequence of symptom or result which we might decide to find. In other words, that the adage of the wish being father to the thought is of special aptitude in medical diagnosis and therapeutics. And this is particularly true of all those remedies that come to us from the microbo-biological laboratory. If we were to judge solely by the mere returns of diminished mortality so prodigally supplied in current literature, the reputation of the serum treatment ought to be firmly established; but with all deference we suggest that these returns may be divided into two classes; the first, consisting of several short series of cases from observers of limited ex- THE SERUM TREATMENT OF DIPHTHERIA. 229 perience, which illustrate nothing, since there has been no distinction made between the mild cases, which, as we all know, have a natural tendency to cure, whatever be the treatment, and the graver class, which must constitute the crucial test. The other, and larger class, is repre- sented almost uniformly by the results in hospitals in which the former mortaUty has been abnormally high. Thus, the return made by Eoux of a mortality of 51 '7 per cent., reduced by serum treatment to 24'5 per cent., gives a ratio hardly better than that attained for some years past, in more than one Metropolitan Eever Hospital, by the old methods. Moreover, as conceded by Moizard, physician to the Trousseau Hospital in Paris, the diminished mortality at that institution (and at many others) may to a large extent be accounted for by the highly necessary hygienic improvements which have been carried out concurrently with the trial of this new remedy. It appears probable that in Serum therapy, as in the case of Antiseptic surgery, the scrupulous cleanliness which is indispensable to it may, quite irrespective of the medicament employed, be a not uniruportant factor in the improvement of results. The subject of serum treatment will be considered by us with all the fulness of detail demanded by the claims advanced on its behalf, and with every direction for its administration as will enable it to be pursued by those desirous of testing its efficiency. No attempt will be made to explain away figures reported by other observers. Indeed, they will but rarely be quoted, for our own conclusions will be illustrated by a com- parison of results in a series of 100 cases treated by the serum, with another series of 100 cases treated without serum, at a corresponding period of the previous year. The following is one of many circumstances of a misleading tendency which led us to take this step of separate and independent observation and comparison. An unofficial report had been published in the Lancet and British Medical. Journal of results in the Isolation Hospitals of London, after hardly more than three weeks' official trial of the remedy, cases being included that had only been admitted one or two days previously. The author of this report thus ascribed a percentage mortality of 4:'6 per cent, on 43 cases at the hospital where we have been watching the treatment — " the lowest mortality on record." Within two days of publication of these figures this mortality became over 8-0 per cent.; three weeks later it was 19 per cent.; and as the figures we have col- lected show, it was finally, at the end of four months, 27 per cent., practically the same mortality as had obtained for the two previous years by the older methods in nearly 2500 cases. Unfortunately,, the first percentage of 4-6 has been largely circulated, and is still accepted and quoted as a record. Again, we personally having stated that out of five cases we had already lost two, were credited in prints widely distributed, with three recoveries out of five cases ; whereas out of our first eight cases only two recovered. 230 • APPENDIX, The history of this method of treating infectious diseases by the injection of some substance which is capable of antagonising its specific poisonous effect is, albeit of some interest, but a short one. The application of the principle cannot be said to have resulted from any one brilliant discovery, but may rather be described as the gradual development and outcome of the labours of many individuals. The scientific investigation of the subject dates from 1860, when Pasteuk made the first announcement of his classical researches upon ferments. Thence he was led to study the mode of action of bacteria, and his labours in this direction prompted Metchnikoff and others to study human reaction to the presence of these pathological micro-organisms. Metchnikoff's epoch-making statement of the part played by phagocytes in the body is known to all ; but it is only fair to say that his conclusions have been vigorously opposed, and albeit they have been deemed reasonable by many competent critics, they must not yet be accepted as absolutely proven. The therapeutic method itself may also be said to date from Pasteur, with his discovery, in 1880, that a mild attack of fowl cholera can be induced in chickens by inoculating them with an attenuated virus, that is to say, with a culture of the pathogenic microbes of the disease, the virulence of which has been reduced by cultivating them in an unsuitable medium, so as to impede attainment of their full virulence. This mild attack rendered the chickens immune to fowl cholera, and the next advance was made by the same investigator when he applied this discovery to anthrax. In some respects vaccination for smallpox, may be said to have foreshadowed these and other similar results ; the difference, however, between them and modern serum therapy consists in the fact that the former, having been pursued on a much less scientific basis, cannot be looked upon as having done more than indicate the practicability of combating disease by methods of inoculation'. THE SERUM TREATMENT OF DIPHTHERIA. 231 In 1886 Salmon and Smith showed that the principle discovered by Pasteur was applicable to liog cholera. Eoux about the same time demonstrated that sterilised cultures of anthrax bacilli induced charhon in the subjects inoculated. In all of these cases it was found that the mild attack excited by inoculation with the attenuated virus rendered the animals immune to further attacks of the same disease, not only in attenuated but in virulent form. A further advance was made when Nuttal, Beheing, Buchnek, TizzoNi, Cattani, and others, showed that recently drawn blood had in certain cases an undoubtedly germicidal power. The same properties were also evinced by aqueous humour, ascitic fluid, and lymph drawn from the dorsal lymph-sinus of the frog. It soon became evident that the blood of different animals exercised, as it were, a specific effect with regard to definite microbes. Thus Behring discovered that blood taken from the rat or the frog was especially efficacious against anthrax bacilli, those animals being peculiarly refractory to the onslaughts of these organisms. It was further demonstrated, after a short time, that the germicidal power of the blood was only effectual within certain limits, and that a definite quantity of it was able to destroy only a correspondingly definite number of bacilli, so that its action was practically that of a neutralising body. Buchnee ascribed this ger- micidal power to an albuminoid substance contained by these fluids. In December 1890 Beheing and Kitasato made the surprising announcement that if an animal is immunised against tetanus or diphtheria, its serum, injected in sufficient quantity into another animal, was able not only to immunise against an attack, but to cure one. Here are the precise terms in which these two observers pub- lished their discovery : — " Our researches on diphtheria (Beheing) and on tetanus (Kitasato) have led us to the question of immunity and cure of these two diseases, and we have succeeded in curing infected animals and in immunising healthy animals, so that they have become incapable of contracting diphtheria or tetanus.'' 232 APPENDIX. After the researches of Beheing, it is only fair to mention those of Aeonson, who, with equal perseverance, succeeded in immunis- ing animals against diphtheria. Hankin, in 1891, succeeded in isolating from the spleen and blood of rats a globulin possessed of germicidal powers, which, in his opinion, constituted the antitoxic or germicidal substance. In the following year Beiegee, Kitasato, and Wasseeman cultivated tetanus bacilli in bouillon, prepared from the thymus of the calf, with the result that the bacilli became non- virulent, and did not form spores. Mice and rabbits, having been inocu- lated with this bouillon, became immune to attacks of tetanus on subsequent introduction of virulent cultures of the bacillus ; and further, blood serum from an immune animal, when injected into a susceptible animal, conferred immunity tipon it. Similar results were also obtained with several other pathogenic bacteria — as, for instance, with the bacilli of typhoid, cholera, and diphtheria. Soon after this, Ogata and Jashuea discovered that when bacilli, previously attenuated by being cultivated in the blood of naturally immune animals, are injected into susceptible animals, they result in a mild attack, which confers subsequent immunity. Aeloing has further shown that the reverse is also true — that is to say, that animals which are naturally immune to anthrax can be rendered susceptible to it if certain substances are mixed with the injection ; and Leo has claimed that white mice, which are naturally immune to glanders bacilli, can be made susceptible by feeding them for some time before they are inoculated with phloridzin. This statement, however, needs confirmation. Thus the last link in the chain was forged, and from this time on it was only necessary to apply the discoveries that had been made. In this field, the work of Beheing has been most productive. The next problem that presented itself was. How can artificially acquired immunity be conveyed from animals to human beings who have acquired the disease ? The supposition that diphtheria is a malady. localised to the throat, for a long time stood in the THE SERUM TREATMENT OF DIPHTHERIA. 233 way of discovering a cure on these lines ; and it was not until it was recognised that diphtheria, albeit of local origin, is a systemic disease, that any advance became possible. It will be well, at this point, to take a general brief review of the treatment of infectious diseases by the introduction into the body of the serum of artificially immunised animals. At the International Congress of Hygiene and Demography, which was held in London in 1891, Hankin pointed out that the bactericidal action of the serum of immune animals is due to the action of certain defensive proteids, and that, whilst some of these act by killing the, microbes, others destroy or neutralise the microbic products. At the same meeting Kitasato again mentioned his discovery in conjunction with Beheing — that the injection of the blood of rabbits which had been rendered immune to tetanus not only renders mice refractory to the affection, but also cures them of the disease when it is already in progress. Sidney Martin (1891), in a special report to the Local Govern- ment Board, further demonstrated the nature of these microbic products as regards diphtheria. Then in 1892 Klemperee stated that the discoveries with regard to diphtheria are also applicable to other infectious diseases, and in March 1893 Klemensiewicz and EsCHEKiCH rendered guinea-pigs immune to inoculation with diphtheria by a preliminary inoculation with the blood serum of patients recovering from the malady. Closely following on this, Behking and Kossel recorded thirty cases of diphtheria in the human subject which had been beneficially treated with immunised serum. In this experience they were supported by Heubnee of Leipzig. The culminating point of enthusiasm was reached by Eoux in his brilliant paper at the Congress of Hygiene and Demo- graphy, which was held at Budapest in 1894. He announced himself as enabled to confirm, by experiments in the Pasteur Institute, all that had been claimed by Behring and other previous workers. He recorded a large number of cases in 234 APPENDIX. which the treatment had been adopted on the human subject, and by comparative statistics, enforced the attention of the whole medical world to a consideration of its claims. In concluding our brief historical review of this fascinating subject, we may mention that Eoux in this address, advanced that " the question of preventive and therapeutic serums was born with the experiments of Maurice Eaynaud on the blood of heifers inoculated for cow-pox ; and with those of Eichet and Hekicourt, on the serum of dogs and rabbits vaccinated against septiciemia (1888)." Lastly, it may be recorded, C. Fkaenkel, Babes, and Fereein, have each made claims to priority in these discoveries which can only receive here the recognition of mention. Theory of Immunisation. — To render an animal immune to the diphtheria toxine, it is held sufficient to accustom it slowly to the action of that toxine. The serum of the animal thus immunised is believed to then become a vaccine, possessing qualities Jiot only preventive, but arrestive and curative. It is declared that this mode of protection is evidently immensely superior to the direct immunisation obtained by injecting the toxine itself, which is, moreover, too slow to be of use in the treatment of an acute disease. In addition, the action of the serum — this second hand product — is claimed to be immediate, with the further property of conferring a temporary immunity. Preparation of the remedy. — We are now in a position to study the processes employed to obtain the toxine, and to render immune the animal which is to furnish the antitoxic serum. A bouillon culture of very virulent Klebs-Loeffler bacilli is added to 2 per cent, peptonised alkaline and sterilised bouillon, in a 2-litre shallow and flat bottomed Hask, so constructed as to give the maximum of surface exposure. After the growth has commenced, each flask is connected by a lateral tube with a wash-bottle containing water, by which a con- THE SERUM TREATMENT OF DIPHTHERIA. 235 tiiiuous current of air is filtered and moistened before passing over the surface of the culture in the flasks.* The whole apparatus is placed in a chamber at 36° C. In three or four weeks the culture is sufficiently strong, and is passed through a Chamberland filter. The resultant is a clear bacilhis-free solution of diphtherial toxine, the virulence of which is tested on guinea-pigs. The next step is to accustom an animal to the action of this toxine, in other words to produce Immunisation of the animal, so that its blood becomes antitoxic. Since large quantities of serum must be available for the treatment of human diphtheria, a large animal — the horse — has been selected in preference to a smaller animal, such as the sheep or goat. Moreover, the horse tolerates the action of the diphtherial toxine well ; it is the easiest large animal to immunise; it is easily bled; its serum is limpid, and according to Edux and Nocard, is not injurious to the human organism. After eliminating the possibility of the presence of glanders and tuberculosis by the mallein and tuberculin tests, the animal is brought into good condition by rest and feeding. The immunising process is begun with ^ to 1 c.c. toxine solution, which is injected hypodermically. A local oedema with a slight rise of temperature follows, and persists for a few days. In three days another ^ or 1 c.c. is injected, and in three days more, 1 c.c. During the next two weeks, about 15 c.c. are given altogether in six separate injections, gradually increasing, till by the end of the sixth week, the horse is receiving from 30 to 40 c.c. three times each week. In ten or twelve weeks, the horse is usually considered sufficiently immune, and the antitoxic power of its serum is tested from time to time. This is done by injecting a guinea- pig with a mixture of a definite quantity of the serum, and a definite quantity of toxine solution of known strength. The urine is tested for albumen from time to time, to note that * These conditions for obtaining the maximum amount of toxine exist naturally in the nasal passages, and suggest the reason why diphtheria in this region is so exceptionally fatal. 236 APPENDIX. the toxine is not producing too much albuminuria, a point to which Roux appears to attach importance. The Serum. — A sterilised canula is introduced into the jugular vein, and 5 to 15 litres of blood are allowed to flow through an india-rubber tube into sterilised bottles, which are then placed in a cool chamber, so that coagulation may take place. The serum having separated, is pipetted or siphoned into sterilised bottles, which, a small piece of camphor being added as a preservative, are then hermetically sealed. To ascertain if the serum is aseptic after this manipulation, it is well to place one or two of the bottles in an incubator at 38° C, for forty-eight hours, by which time any micro-organismal growth will have become apparent. The next step is to test the antitoxic power of the serum. Suppose we take ten times the minimum dose of this toxine solution, which would be lethal for a guinea-pig, and call it 1 ; we then mix it with -3, -25, and '1 c.c. of the serum we are testing, and inject one of these mixtures into each of three guinea-pigs of similar weight. If the first develops no symptoms whatever, the second a little local oedema, and the last dies, we conclude that •3 c.c. of this serum is required to neutralise ten times the minimum lethal dose of our toxine solution. A serum, of which , '1 c.c. neutralises ten times the minimum lethal dose of our toxine solution, is what Behring has named normal antitoxic serum, and 1 c.c. of this has a value which he calls an imrmcnisation unit. He says that a single dose of .500 units is required, and is usually sufficient, to cure a child; but as 500 c.c. is too much for injection to produce a practicable dose, the horse must be inoculated with toxine till it affords a serum 50 or 100 times more active than the serum called normal. Behring's iirm send it out in three strengths, as follows : — No. 1, containing 600 units, is suitable at the outset of ordinary cases in children. No. 2, containing 1000 units, is for severe cases hx children. THE SERUM TREATMENT OF DIPHTHERIA. 237 No. 3, containing 1500 units, is for adults and very severe cases in children. It is very essential to keep the vials containing the serum in a cool place, not to expose them to light, and to keep the bottles carefully corked or stoppered; each bottle is stated to contain one dose of the respective serum, but the bottles being all the same size, this implies that the dose is the same in all cases. Theory of the action of antitoxic serum. — One of the difficulties in accepting this novel treatment by clinicians of experience has been that, close as is the connection between each link in the chain of bacteriological research, and precise as the deductions are by which the result has been attained, the adoption of the remedy as such is purely empirical, since its mode of action remains unknown to us. There is no shutting the eyes to the fact that we are entirely ignorant of the chemical nature of toxines and antitoxines, and that before we can pursue this treatment rationally, we will have to understand their chemical composition. If we could isolate and identify the active principle or principles on which the value of antitoxic serum depends, with as much accuracy as we can isolate strychnine or morphine, then we would have something definite to work with. A great difficulty in attaining this is that these bodies exist in almost imponderable quantities. But the ad- vantage of such information would be that we could employ only the beneficial principle, and reject the unnecessary and possibly noxious constituents of the complex body which we in our present ignorance call " antitoxin," and of the still more complex " antitoxic serum." We note with satisfaction that this vitally important subject has been adopted as the first for investigation under the terms of a munificent gift by a City Company for the purpose of further research into the many problems of diphtheria which still remain unsolved; and that the work has been intrusted to Ur. Sidney Martin, to whom we are already so deeply indebted for valuable contributions to the toxicology of the disease. 238 APPENDIX. If one could only accept the theory of phagocytosis in its entirety, one would then be able to appreciate the action of the remedy as a cell stimulant, and, indeed, Metchnikoff prefers to call antitoxins stimulines. On this hypothesis we can understand why such a propor- tionately larger dose is used for children than for adults. Not a few practitioners are said to have failed with this method of treatment in children, believing that the announced dose repre- sented that suitable for an adult. But no such regulation appears to obtain with regard to administration of the serum, for we are taught that an infant or child of tender years can with advantage receive with good effect an equally large dose as would be necessary to prescribe for an adult; and often double or three times the quantity. In other words, an infant weighing twenty- five pounds is placed on a level, in regard to dosage, with a man of twenty-five years. We ought to take it then that the apparent gravity of the attack rather than either the age or the weight, is to be the indication. If this is so, may we seek an explanation in the fact that the younger the child the greater the susceptibility to the disease, and the less the resistance ? Consequently, if, as is suggested, the remedy acts by cell stimulation, the greater the necessity for a large dose of the serum ; or, in other words, since the young cell elements are so extremely sensitive to the diphtherial poison, they require to be fortified all the more strongly in order to exercise an effective resistance. An alternative view of the rationale, of its mode of action is that of Klein, who holds that the toxines circulating in the tissues of the patient are neutralised by the antitoxin, without the inter- vention of the biological factor which is implied in Metchnikoff's theory. The same authority has proposed another method of rendering the horse immune. So far as we understand, it is as follows :— At the commencement of the process, a few injections are made with cultures of attenuated bacilli along with their toxic products. THE SERUM TREATMENT OF DIPHTHERIA. 239 The animal having thus acquired a certain amount of resistance to diphtheria, large quantities of toxine-free bacilli are repeatedly injected subcutaneously — each injection gradually increasing in virulence. By this method, Klein claims to have obtained serum of sufficient antitoxic power in as early as twenty-three days, whereas, Eoux, whose method is practically identical with that of Behring, by more numerous injections of toxine of definite strength, has not succeeded in effecting this end under ten weeks. In Klein's process, the amount of toxine is not definite; its strengtli and amount depending on the varying numbers and virulence of the bacilli introduced. Indications for serum treatment. — The essential one is the presence of the Klebs-Loeffler bacillus, either with or without associated microbes. But when a child, attacked by diphtheria or croup, presents symptoms of broncho-pneumonia, it is in our experience, as in that of many other observers, utterly useless to employ serum, and, indeed, it does positive harm if pulmonary tuberculosis be present. In one instance of which we have knowledge an injection of serum appeared to be directly respon- sible for a recrudescence of spondylitis. Dosage. — It is impossible in the present state of our knowledge to fix the dose of serum on the datum of age, as is the case with the generality of remedies. The first dose may be regulated according to the length of time which has elapsed since the onset ; and later, after a bacteriological examination has been made, the question of a repetition or of an increased dose may depend on whether the bacillus is or is not accompanied by the virulence- conferring streptococcus — in other words, if the case has proved, on bacterioscopic examination, to be a severe one. Eoux's first announcement, speaking of the serum from the Pasteur Institute, was to give 20 c.c. to every patient — adult, or child above one year, so soon as admitted, and even in advance of the bacteriological diagnosis, stating that for children under one year the first dose should be as many c.c. as the child is months old. 240 APPENDIX. In very severe cases, Eoux states that the dose may be as much as 30 c.c. and even more, notably in those in which it has been found necessary to practise tracheotomy. The following has been our experience, the serum employed having been that prepared at the British Institute of Preventive Medicine, and indicated in our records by the letters B.I.P.M. : — More than 20 c.c. has never been given as a first dose for an adult, and the average has been 15 c.c. for a child between one and five years. For a child under one year, treatment has commenced with 10 c.c. The number of repetitions and amounts of the repeated doses have been regulated mainly by the disposition of the membrane to separate, and by its effects on the temperature, circulation, respiration, and renal secretion. We are in accordance with those who advise that there should be an interval of twenty-four hours between the first and second injections. It appears preferable to make the first dose a fairly large one ; whether the following doses, if any, are to be more or less must depend on the circumstances of each individual ease. The largest total quantity which we have seen administered was to a girl of nine years, 120 c.c. in eight equal doses. Many cases required but one dose, and seldom more than three. To those who desire to use other preparations of serum, the following table may be useful : — Preparation. Dose in C.C. Dose in Fluid Drachms. Roux (Pasteur Institute), 10 to 30 24 to 74 Brit. Inst, of Prev. Medicine (B. I. P. M.), . 10 to 20 2i to5 Burroughs, Wellcome, and Co. (B. & W.), . . 10 to 20 24 to 5 Klein, 6 to 10 14 to 24 Aronson 2 to 5 itolj Behring (in three strengths), . 8 2 Eoux's serum is not to be obtained in this country. The syringe should be sterilised both before and after beina THE SERUM TREATMENT OF DIRHTHERIA. 241 used ; we prefer that kind called Eonx's (Fig. 63), made by Arnold, but that of Burroughs and Wellcome is equally suitable (Fig. 64). The following are the precautions to be observed during the employment of serum treatment :— The syringe having been taken to pieces, the separated parts Fig. 63. — Eoux's Sybingk i'Ok Antitoxin, showing how each separate part can be disjointed for the purpose of disinfection. are immersed in cold water, which should then be boiled for five minutes. They are then carefully dried. The india-rubber tube Fig. 64. — Bubroughs & Wellcome's Antitoxin Syringe, also capable of easy and efficient disinfection. is sterilised by forcing through it a stream of boiling water by aid of the syringe. The skin is washed with an antiseptic lotion, and having selected the lower lumbar or inguinal region, the skin is pinched up by the left thumb aird forefinger, the needle introduced, and the serum 242 APPENDIX. injected slowly. A pad of sublimate wool is placed over the site of puncture, and, with the exuding drop of serum, forms a sort of collodion. A local oedema is produced, which usually disappears within an hour. Results. — Many claims have been made as to the advantages of the so-called antitoxin or serum treatment of diphtheria over the former methods, but no comparative statistics have hitherto been furnished beyond those of mortality. These we now propose to supply by figures derived and classified from a series of 100 cases treated by the serum, as noted in the wards of a metropolitan fever hospital in the first four months of the present year, having taken advantage of the facilities afforded by the Metropolitan Asylums' Board to follow the course and treatment of this and other in- fectious diseases in the wards of their excellently administered hospitals. These results will be compared with the figures of another series of 100 cases, treated without the serum, in the same hospital at a corresponding period in the previous year, and therefore under exactly similar circumstances of situation, season, administration, and hygiene. This series of results under former methods is a somewhat detailed resumA of a portion of the pub- lished statistics for the year 1894. We have not failed to recognise the objections which may be made, and quite legitimately, against this comparative method of reviewing the subject. The first and most important one, viz., the absence of bacteriological diagnosis in the series of cases treated without serum, may be met by the reply that this cir- cumstance has not been held to reflect adversely on comparisons made in favour of the new treatment; and also by the well- ascertained fact that, in the institution in which these cases have been observed, the proportion of errors in the clinical diagnosis corrected by bacteriological methods has been so extremely small (less than 5 per cent.) that the discrepancy may be almost dis- counted. Other objections and possible sources of fallacy will be met as they occur on consideration of the various headings to be now discussed. THE SERUM TREATMENT OF DIPHTHERIA. 243 The points thus offered for comparison will be found to touch on almost every particular that has been advanced in favour of serum treatment : — 1. The mortality, actual, and as calculated for age periods. 2. The mortality after deducting eases fatal within twenty-four hours of admission. 3. The day of the disease on which treatment was commenced. 4. The prolongation of life in cases with fatal results. 5. The site of the membrane. 6. The day of treatment on which the membrane commenced to separate. 7. The day on which the throat was declared free of membrane. Under this heading will be subordinately considered the disposi-^ tion for membrane to extend, and to re-appear. 8. The temperature. 9. The pulse. 10. Skin eruptions and joint pains. 11. Adenitis. 12. Otorrhoea. 13. Eenal complications : — (a.) Albumen ; (6.) Urea ; (c.) Phosphaturia ; (d) Anuria ; (e.) Nephritis. 14. Cardiac failure. 15. Other causes of death. 16. Paralytic sequelae. 17. General well-being during treatment and convalescence. The serum employed was in all cases that provided by the British Institute of Preventive Medicine. Series " A " refers to cases under former treatment, and Series " B " to those under serum treatment. The latter comprises 61 completed cases, the first treated on January 2nd, 1895, and 39 who were still in hospital on April 30th — the last day of our observation — none of them having been admitted later than April 8th. 244 APPENDIX. According to seasonal mortality curves, the first three months of the year may be taken to represent a period of average fatality, and in the opinion of the Medical Superintendent of the hospital under observation, the disease, as witnessed in the early part of the present year, differed from the average rather on the side of increased mildness {Lancet, Feb. 2, 1895). The following division of our 1000 cases, in which there were 284 deaths, into separate hundreds, shows how uncertain these variations of mortality are : — 1st hundred. 2nd. 3rd. 4th. 5th. 6th. rth. 8th. 9th. 10th. 30 27 26 36 32 37 20 30 24 22 1. The actual mortality in both series now under comparison was the same, namely 27. It was 27'10 on the whole mjmber — 1163 — treated during the year 1894 at the hospital whence our comparisons were made. This fact, that the mortality in those under classical treat- ment represents the exact proportion observed in the total for the year 1894, shows that the series may be accepted as in every respect a fair standard for comparison with that under serum. On this point of mortality it is of course all-important to select as a basis of comparison, not the results at institutions of which examples may be found in any of the Continental cities, where the former mortality has ranged between 40 and 60 per cent., but the returns of hospitals which have shown the best results under former treatment. To reduce a mortality, as in the case of Eoux's Parisian statistics from 51-7 to 24-5, or of those of Budapesth under Bokai from 60'23 to 25-83, must carry a different impression to the physicians of the hospital where such cases are treated than it will to those who have been accustomed by long experience to a mortality of 26 or 27 per cent., as is recorded of one or two of our metropolitan isolation hospitals. THE SERUM TREATMENT OF DIPHTHERIA. 245 London, indeed, is not free from the^e discrepancies, for in these hospitals, all under equal conditions of administration, a difference in death rate may from year to year be observed to the extent of 13 or 14 per cent. In other words, the mortality in the hospital with the highest death rate can be seen to be half as high again as that in the hospital in which it is lowest ; nor can this difference in results be due to variations in type of the disease in any one particular metropolitan district, because it is well known that patients are admitted into our fever hospitals, not according to district but according to accommodation, a return of which is daily made to the central oftice. Mortality at age periods. One of the strongest claims advanced in favour of serum treat- ment has been that infant mortality has been markedly decreased under its use, but the following figures illustrate that so far as age was concerned, while the number of cases under five was consider- ably in excess in Series " A," the mortality was less by over 10 per cent. On the other hand, there is an improvement in the results at the more advanced age periods in Series " B." Series "A '—27 deaths. Series " B "—27 deaths. Age. Number of Cases. Number of Deaths. Mortality per cent. Number of Cases. Number of Deaths. Mortality per cent. Under 5 5 to 10 Over 10 51 28 21 22 3 2 43-1 107 9-5 43 37 20 23 3 1 53-48 8-1 5-0 rive cases were over 21 years of age, ranging from 22 to 36. Eight cases ranged from 21 to 39. Under former methods, no deduction can be made for withheld treatment in the case of patients adnjitted moribund or declared beyond hope, a circumstance which has undoubtedly obtained in many hospitals where serum treatment has been pursued on a large scale, and naturally to the advantage of their statistics. 246 APPENDIX. If, however, allowance were to be made in both instances for eases which have proved fatal within twenty-four hours after admission, as has been very generally urged by all advocates of serum treatment, the result would not, according to our figures, be in favour of serum. 2. Mortality after deducting cases fatal within twenty- four hours of admission. Series "A." Series " B." Age. Deaths within twenty-four hours. Reduced Mortality. Deaths within twenty-four hours. Reduced Mortality. Under 5 5 to 10 Over 10 10 1 21-5 7-1 9-5 3 46-5 8-1 5-0 At the hospital from which these figures were taken, 1249 cases of diphtheria were treated in 1893, with a total mortality of 332, or 26-4 per cent. Had allowance been made for 49 cases which died within 24 hours of admission, this mortality would have been reduced to 283, otherwise to 22-6 per cent. The total mortality for 1894 in this same hospital was 314 out of 1163 cases treated, or 2710 per cent. With similar allowance, the mortality would be reduced by 41 cases, in other words to 23 '4 per cent. 3. The day of the disease on which treatment was com- menced. A claim has been strongly urged for commencing the serum injections at the earliest possible moment, and elaborate figures have been prepared, showing the increased mortality in proportion to the delay in its adoption. But such a proviso should surely apply not only to diphtheria and to a particular treatment, but to every disease and to all therapeutic measures. In hospitals for diphtheria, where it is the rule for nurses who have the least symptom of sore throat to present themselves to the medical superintendent for immediate examination, and where THE SERUM TREATMENT OF DIPHTHERIA. 247 the disease is, therefore, attacked at once, a fatal result is almost unknown, and this under the former methods of treatment. In the hospital in which these observations were made, 42 cases of diphtheria have occurred in the staff during the last five years, without a single fatal result. The following figures show that there is no warrant for special application of the general law that the earlier the treatment the better the result, since the day of admission was practically equal in both series : — Day of Commence- ment of Treatment. Series "A." Number of Cases. ■ Series " B." Number of Cases. 1 2 3 4 5 Over 5 2 29 22 20 8 19 2 24 32 17 9 16 4. The following figures show the prolongation of life in cases with fatal results : — Number of Deaths. Day of Death. Series "A." Series "B." Within 24 hours, 11 3 2nd day, 2 1 3rd 4 3 4th 3 4 5th , 1 2 6th 3 1 7th , 1 1 8th , 1 4 9th , 1 10th , 1 16th , 1 21st , 1 32nd , 1 38th , 1 The average length of time before the fatal termination was 3-3 days in Series " k" whereas in Series " B " it was 8-79. 248 APPENDIX. This prolongation of life has been claimed as an advantage of serum, and without doubt, as a general rule, it implies an increased chance of recovery; but in the case under consideration it is capable of a contrary interpretation, for it would appear to indicate the acquirement of something in the system which entails a longer time for full elimination of the toxin of the disease, with a consequent diminution of recuperative energy, and final failure. Thus, while in all serum eases there is a tendency for convalescence to be delayed, in those terminating fatally, death is simply pro- crastinated, and the period of suffering of the patient and of anxiety to the parents is unduly extended. 5. The site of membrane is to be considered as an important indication of the relative gravity of the two series of cases, and although Series " A " has fewer examples of nasal diphtheria — the most fatal form — -pe-r contra, it has many more examples in which the membrane extended to the larynx, and a larger number of tracheotomies. Site of Membrane. Series " A." Series "B." Fauces, . . ... Larynx, Fauces and Larynx, Faucial and Nasal, Faucial, Nasal, and Laryngeal, Nasal, Hard Palate, Faucial and Palatal, Faucial and Buccal, Faucial and Vulval, 60 2 16 17 1 1 1 1 1 65 3 28 2 1 1 With regard to nasal diphtheria, whether in association with the fauces or larynx, or both, we have found in 1000 cases, tabulated with regard to site and other items of interest, that this variety was fatal in 67 per cent. ; and in the present comparison we find in Series " B " a total of 31 cases of this class, 16 of which ended fatally — in other words, 5016 per cent. This is in favour of the serum, for under the older method of treatment, as repre- THE SERUM TREATMENT OF DIPHTHERIA. 249 sented in Series "A," out of a total of 19 cases, 12 died— or 63-15 per cent. In the cases in which the larynx, was involved, in Series " A," 7 died without operation, out of a total of 18 ; these included one case which died within twenty-fours of entrance to the hospital, intubation having been performed previous to admission; 4 tracheo- tomies were performed, of which number 2 died. In Series " B " there were 5 eases of laryngeal diphtheria, and of these 2 died ; in one of the fatal cases tracheotomy was performed. These numbers are certainly too small to deal with, but evidence from other sources is distinctly in favour of serum treatment with regard to laryngeal diphtheria. 6. The day of treatment on which the membrane com menced to separate. According to Eoux and many other observers, the false membranes cease to spread at the end of twenty-four hours, commence to be detached twenty-four hours later, and do not persist more than four or five days. The early experience of English observers — ourselves amongst the number — tended to agreement with these statements. The membrane was generally reported to early undergo a whitening process, a Assuring of its surface resembling the "crackle" marks on old china, and a notable eversion of the edges. When it separated there appeared to be certainly less bleeding from the underlying tissue, and less haemorrhage was observed to follow assistance in removal of semi- detached portions. Evidence was given that the membranes, when separated, showed little disposition to re-deposit. When, however, these articles of assertion and belief come to be tested by figures, not much is really found to the advantage of serum on this point. It requires to be noted particularly that this point of speedy separation was not attended to very much under the pre-serum methods of treatment. Consequently we have only 50 cases in Series " A " from which to draw comparisons. It is to be understood, with regard to the serum series, that 250 APPENDIX. an injection was always made immediately on admission to the patient. Day. Series " A " (on 60 Cases). Series " B " (100 Cases). 1, • 2, . 3,. 4,. 5,. 7, . 12, . 10 or = 20 per cent. 13 „ = 26 18 „ = 36 7 „ = 14 2 „ = 4 1 per cent. 28 „ 36 „ 14 „ 2 1 1 The full number of 100 is made up in Series " B " by 2 eases in which no membrane was visible, 2 in which there was further exten- sion, and 13 in which death occurring the membrane had not cleared. 7. The day on which the throat was declared free of membrane. In Series " A " this fact was noted in only 67 of the cases, and in 92 in Series "B." Only 1 occurred in which membrane re- appeared, and that on the fourteenth day after admission ; whereas in Series " B " there were 5 cases of re-appearance, 13 cases in which it never cleared entirely, and in 1 case it was observed as late as the thirty-ninth day after admission, and the forty-first day of the disease. Day. Series "A." Series "B." 2. 4 or = 6 per cent. 1 or = 1-08 per cent. 3. 13 „ = 20 4 „ = 4-3 4. 14 „ = 21 9 „ = 9-8 5. 14 „ = 21 18 „ = 19-5 6. 8 „ = 12 18 „ = 19-5 7. 6 „ = 9 10 „ = 10-8 8. 5 „ = 7-4 „ 2 „ = 2-1 9. 1 „ = 1-.5 „ 1 „ = 1-08 10. 1 „ = 1-5 „ 1 „ = 1-08 11. 1 „ = 1-5 „ „ = — 12. — 2 „ = 2-1 13. — 2 „ = 21 14. — 2 „ = 2-1 17. — 1 >. = 1-08 24. — 1 „ = 1-08 28. — 1 „ = 1-08 39. — 1 „ = 1-08 67 74 + 18 as above = 92. THE SERUM TREATMENT OF DIPHTHERIA. 251 Eoux also affirms that the specific bacilli disappear with the clearing off of the membrane, or in at most a few days after that event. With this our experience does not agree, since in very many cases the bacilli are proved to be present for several weeks after the attack has passed, in spite of attempts to hurry their departure by means of antiseptic gargles and mouth-washes used twice and three times daily. In one instance under our observation the patient was still detained in hospital on account of the continued presence of bacilli as many as one hundred and forty -six days after all signs of membrane had disappeared. Probably removal to a convalescent hospital might effect the desired end in such persistent cases, care being taken to keep them isolated from those recovering from other infectious diseases. 8. As to the temperature, no exact comparisons can, of course, be made, but we must again call attention to the fact that in diphtheria the thermometer by no means ranges high, and is always low, even subnormal, after full appearance of the membrane, that is, after the second or third day. We, therefore, cannot appreciate the point made as to reductions in the " fever " of the disease. In no case have we seen any notable reduction in temperature after an injection of serum, as has been so frequently stated. On the contrary, there is almost always a rise, small it may be, and often of but a few hours in duration. We have no desire to magnify the importance of this matter of fact, but we agree with the remark of Variot that an elevation may be easily overlooked unless the thermometer be used at least every four hours. In non-diphtherial cases of membranous throat, this physician has noted that each injection of serum causes a rise of temperature of from half to one degree, and sometimes more. The temperature in pure diphtherial cases, according to Louis Martin, falls after twelve hours, but had he recorded the tempera- ture more frequently than twice a day, as his published charts only show, it is not unlikely that this fall would have been noticed to 252 APPENDIX. be preceded by the slight rise of temperature soon after the injection, of which it has been thought a duty to make note. In cases in which the streptococcus is associated with the diphtheria bacillus, L. Martin notes a rapid rise of about one degree after some of the injections. An examination of his charts of complex diphtheria reveals the fact that it is the rule for the second injection to be followed by a gradual rise of temperature for twenty-four hours, whereas, in purely diphtherial cases, the second and subsequeiit doses are not, as a rule, followed by elevation. 9. As to the pulse, after a dose of serum has been administered we find the rate somewhat increased concurrently with the rise in temperature — in one instance it went up immediately from 136 to 166 ; and we have been unable to detect any diminution in tension, as has been claimed by some observers. In pure diphtheria of a mild type, the first dose, according to L. Martin, at once diminishes the pulse rate ; but with streptococcal associations there is a very marked increase, always after the first, and sometimes after the second. Variot has lately drawn attention to the quickening of the heart's action, cardiac asthenia, and arhythmia of the pulse, as a sequel of injection of serum. 10. Skin eruptions and joint pains constitute another element on which no comparison can be made, for in Series " A " rashes were practically, and joint pains absolutely, absent. In one case erythema nodosum was observed, and in another, a male aged thirty-five, eczema was present on admission. In Series " B," 38 of the cases developed eruptions which varied in occurrence from the seventh to the twelfth day, and were of the varieties which have been generally recorded. In several instances, when a fresh injection was made, after an interval of some days, the eruption broke out anew. In four cases there were joint pains. Our figures are greatly in excess of those recorded by Moizard THE SERUM TREATMENT OF DIPHTHERIA. 253 who, out of 231 cases treated by serum, noted 33 rashes, namely, 14 of urticaria, 9 of scarlatiniform erythema, 9 of polymorphous erythema, and 1 of purpuia. This physician reports that urticaria is noticed at a period varying from a few hours to as many as fifteen days after injection. It is seen more or less over the whole body, in successive crops, and unaccompanied as a rule by high temperature. The erythematous form of eruption is more severe, as it is accompanied by high temperature, and, as Moizard relates by phosphaturia. Joint pains, simulating those of acute rheuma- tism, are distinctly more common under serum treatment; they are rarely found along with a rash, and are less frequent than skin eruptions. We have already noted in our chapter on clinical diagnosis that rashes are not unknown in diphtheria, but under serum treatment they are decidedly more common, occur at a different stage, and also in non-diphtherial cases in which serum has been used. Besides, joint pains in pre- antitoxin days were practically unknown, except in cases of complex diphtheria of malignant type. It has been advanced by laboratory workers that these eruptions and articular swellings are of no clinical importance. This opinion requires no refutation from a clinician; for such accidents, whether rare or frequent, mild or severe, clearly indi- cate a truly toxic origin. The serum coming from certain horses has been observed to have a more marked toxic effect, due, perhaps, to the species, age, or state of health of the animal, for clearly it cannot be guaranteed that absence of glanders or tubercle exhausts the whole gamut of possible blood infections. Does this suggestion offer the explana- tion of a difference between 38 per cent, of such undesirable effects of the remedy in our series of 100 cases as distinguished from 14-3 per cent, in the much larger series of Moizard ? With- out offering a reply, it would be well to avert the possibility of such an insinuation by employing a serum more capable of being accurately tested with regard to uniformity and purity. The suggestion of Fraser and Euffer to evaporate the serum in vacuo, 254 APPENDIX. and to obtain the antitoxic body in a solid form, to be dissolved in water before use, is a good one. Klein, we understand, is now working with this same object in view. 11. Adenitis was observed in 18 cases in Series " A," and in 28 cases in Series " B." In some instances the serum injection appeared to lead to a rapid, although sometimes only temporary, diminution in glandular enlargement where it existed on admission. The proportion of cases which went on to suppuration was about eqiial in the two. In connection with this question of suppuration, we may mention that there were two cases of abscess at the site of injection. The following is an example. A female child, aged 5 years, admitted January 10th, 1895, on the third day of her illness, which began with rigors and sore throat. On admission. — Membrane was observed in a thick mass on the right tonsil, which was enlarged ; the cervical glands on the same side being swollen and tender. Temperature, 98-2°; ^Ise, 100. 15 c.c. of serum (B. I. P. M.) were injected with the ordinary pre- cautions under the skin of the abdomen in the lower part of the right flank. January ISfh. — Membrane entirely gone, the throat appearing quite clean. Temperature, 98-2°; pulse, 100. February 9th, — There is a fluctuating swelling over the site of the injection about the size of a Tangerine orange, fairly circumscribed, and surrounded by a hypersemic zone; it is very tender to touch, and painful when the child attempts to move. Temperature, 100° F. ; pulse, 108. February IQth. — Under chloroform the swelling was incised, and a quantity of thin pus was evacuated. On examination the abscess sac was found to be multiple ; the whole cavity was thoroughly washed out with warm boracic solution, and a drainage tube inserted. Temperature, 100-2°. February I2th. — Doing very well, though a large opening remains where the abscess formed. Temperature, 99°. February 20th. — Wound healing. Temperature normal. Buffer has remarked how difficult it is to preserve the serum aseptic during the process of preparation, and to this cause we must attribute a certain proportion of the accidents of the treatment. THE SERUM TREATMENT OF DIPHTHERIA. 255 for they have occurred too generally to warrant any suggestion as to neglect of antiseptic precautions in particular cases. 12. Otorrhoea. This is a complication of admitted occurrence in the course of diphtheria, irrespective of treatment. It was noted 13 times in Series " A/' and 16 times in Series " B." 13. Renal Complications : — (a) Albuminuria. — This also is a recognised symptom of diph- theria. It was found 38 times in Series "A," and 50 times in Series "B." There is no necessity to quote figures illustrating the varying quantity under the two methods, but it may be stated that it was developed in decidedly larger amounts in Series " B." Both (6) urea, and (c) phosphates, have also, under serum treat- ment, been observed in excess of what may be called the amount normal to diphtheria. It is a well-known fact that the albumen of even a non- medicated heterogeneous serum introduced into the economy results in albuminuria ; and we have noted that this evidence of renal overwork has increased in frequency since the employment of serum. Lupine of Lyons, admitting that albuminuria super- venes just after the first injection of serum, asserts that it has no gravity and has no influence on the persistence of a diphtherial albuminuria; but, according to Eoux, nephritis and albuminuria are less common than under former treatment. Moizard, physician to the Trousseau Hospital in Paris, agrees with him, saying that albuminuria is no more frequent under serum treatment than it was formerly, and believes, with Eoux, that renal lesions are due rather to diphtherial toxaemia than to antitoxin. Euffer goes even further, and in the Medical Annual for the current year, wishes " emphatically to state that there is not the slightest foundation for Mr. Lennox Browne's statement that the antitoxic serum does cause any suppression of urine." 256 APPENDIX. But all these opinions are opposed to the results of the equally careful observations of Oertel, Eitter, Siegert, Variot, and many others, who accuse serum of directly provoking albuminuria. It is difficult to account for these contrary opinions, the practical outcome of which is that while some authorities state that the timely administration of serum prevents renal complications, and others that albuminuria indicates renewed doses of serum, a last set, of which we declare ourselves adherents, believe that marked and increased albuminuria, especially if accompanied by diminished quantity of urine, should be accepted as contra-indicating a con- tinuance of the injections. (cf.) Anuria. — Hansemann was the first to draw attention to the increased liability to anuria under serum treatment. We were particularly unfortunate in our own early experience in this respect, six patients out of a series of eight, and not inchided in the present comparison, dying with anuria as the most prominent symptom. In the series reported by Washbourn and Goodall, in which ten fatal cases were said to be due to cardiac failure, further information showed that in six of the ten there was partial anuria, and in one total anuria for the last fifty-three hours of life, the patient dying on the ninth day after the first injection ; in one we learn that cardiac failure was secondary to con- vulsions, but it is not stated whether, as it is fair to presume, the convulsions were due to uraemia, or if, in this case, there was anuria, partial or total. Anuria, therefore, was evidenced in 7, if not 8 of the 10 fatal results. Our table of 1000 cases shows that this is a notable increase on the average of this occurrence as exhibited under " classical " treatment. It has been asked, with regard to anuria and nephritis, if the serum would determine nephritis, how was it that there was not albuminuria in non-diphtheritic cases treated by this remedy (Lancet, Vol. II., 1894, p. 1539). But argument based on such an hypothesis is clearly illogical; no one has advanced the view that the serum will produce anuria in a patient who is not suffering from diphtheria, but only that it increasfes the well- THE SERUM TREATMENT OF DIPHTHERIA. 257 known tendency to renal complications in those intoxicated with its specific poison. However that may be, the figures show that this complication is of less common occurrence in series " A " than in series " B/' the numbers being respectively 2 and 7. Many of these cases of suppression of urine bear out the fact that anuria often supervenes, not gradually, but almost suddenly, and therefore depends frequently on a paralysis of the renal vaso- motor system, to which parenchymatous degeneration, when it exists, is secondary. This would account for the circumstance that occasionally, when the anuria has been rapidly fatal and short in duration, the post-mortem appearances of the kidney, both macro- scopic and microscopic, have given absolutely no evidence of morbid change. (e.) Nephritis. — During 1893, out of a total of 2848 cases treated in all the Metropolitan Asylums' Board Hospitals, with 865 deaths, 8 cases of nephritis were reported. In Series " B," out of the 7 cases of anuria, nephritis was proved to exist post-mortem in all the 5 in which a necropsy was allowed, as well as in 4 other cases in which death resulted from other causes. In short, in all the 9 cases in which a necropsy has been permitted, out of the total of 27 deaths, nephritis has been revealed, and sometimes in extreme degree. The peculiar conditions were as follows : the distance between each two pyramids was diminished and the apices of the pyramids flattened; in many there were haemorrhagic evidences while the capsule was sometimes firmly adherent. These figures are in accordance with those of Benda, pathological prosector to the Urban Hospital, Berlin, who has stated that on necropsy of 39 diphtheria patients treated by the serum only 6 were free from nephritis; 8 showed severe and 25 slighter parenchymatous inflammation. Hansemann, in a personal letter to the author, referring to a case of a child who died of nephritis after injections of serum, says it seems to him " quite indubitable that the nephritis was the result of the large doses of serum which the child had received," and he E 2S8 APPENDIX. goes on to say that, " it is known that serum from one animal pro- duces decomposition of the blood of another when introduced into it. This injurious influence may be all the greater, especially as we have no control as to whether the horses are thoroughly sound." Treymann has reported a case of hasmorrhagic nephritis in a child aged three years. Behring's serum was employed in large doses, "owing to the unfavourable condition of the child in the early days of the disease. About the fifteenth day, albumen, blood, and casts appeared in the urine, and at the same time a measles-like eruption, with high tempera- ture. Four days later there was anuria, lasting for forty- eight hours, and oedema of the eyelids. As the hsemorrhagie nephritis appeared during convalescence, and shortly after the last dose of the serum, and disappeared in an unusually short time, the author thinks that it shou.ld be attributed to the serum. Later, diphtheritic paralysis supervened in this case." Opposed to this is a record of the same nature by Schwalbe, in which hsemorrhagie nephritis occurred in a case treated before the introduction of antitoxin. This author remarks on the rarity of the occurrence in diphtheria, as contrasted with the nephritis of scarlet fever, and justly urges " that the same caution exercised in attributing favourable results to the serum treatment should also be adopted in assigning to it harmful complications." Our figures show a very considerable and undoubted increase in the proportion of cases of nephritis under serum treatment as compared with the old, for in our tabulated list of 1.000 cases, mortality due to nephritis was calculated as at only 2-7 per cent., whereas under serum it has been proved on necropsy to be present in one-third of the cases — 9 out of 27 — and from the imiformity of its occurrence in all those examined, may be fairly assumed to have existed in a similar proportion to that observed by Benda in Berlin — namely, 84-6 per cent. Our experience is quite in accord with those who believe that liability to this complication increases with the delay in ad- THE SERUM TREATMENT OF DIPHTHERIA. 259 ministering the serum, a period of the disease occurring at which antitoxin exercises a marked toxic effect. With regard to this parti- cular and vitally important question, it may again be asked, can the difference of experience and opinion be accounted for by varia- tion in the qualities of the serum employed ? As these pages are passing through the press, the statistical report •of theMetropolitanAsylums' Board for 1894 has been published, from which we learn that 84 cases of nephritis — occurring in a total 3666 cases treated, with 1035 deaths — were reported as a complica- tion, representing a discrepancy of "9 per cent, in 1893, as against 8 per cent, in 1894. But as the larger number includes 68 cases from one hospital out of a total of 642, while another does not show a single one out of 598, perhaps not much reliance is to be placed on these figures, and they are here given rather to enforce the desirability of a greater accuracy in recording these and other complications. It is only fair to quote the experience of Professor Baginsky, which comes to us still later. On a comparison of 993 _ cases without serum and 525 with, he has come to the conclusion that the injection of serum does not increase the frequency of nephritis, giving tables in support of his contention. This observer is careful to give separate and widely differing figures for " clinical nephritis " as distinguished from that observed post-mortem. 14. Cardiac failure. There was only 1 sudden death noted from Series " A " due to cardiac syncope, whereas 4 occurred in Series " B," and here it is again permissible to quote the experience of Washbourn and Goodall, who, ascribing 10 deaths to the poison of the disease out of 61 cases of true diphtheria treated by serum, afterwards reported, in response to enquiries, that all these died of cardiac failure. In a debate on antitoxin reported early in the present year, Baginsky remarked that " he thought attention should be paid to symptoms of cardiac failure, which seemed to be dispropor- tionately frequent in the recent epidemic, for most of those dying 26o APPENDIX. under the treatment died from cardiac asthenia." But quite recently he was reported in the Lancet to have said at Munich that " cardiac debility was very rare, and myocarditis was seldom found by post-TTiortem examination.'' The professors position would appear to be with regard to the heart — that minor degrees of disturbance are met with more often, the severer less often, with the serum treatment. On the other hand, Eauchfuss, of St. Petersburg, is reported in the Lancet to have said at Munich that, "under antitoxin, myocarditis was more frequent ; perhaps that might be due to the fact that a greater number of patients remained alive." It is somewhat difficult to understand how this condition could be judged to have been more frequent, except as a result of post-mortem examinations. 15. Of other causes of death in Series " B," 6 were due to broncho-pneumonia, and 1 to septic peritonitis. We may here revert to the very long period in which the patient's life is held, in the balance in serum treatment, the scale being in the end but too frequently turned adversely. Lastly, we must draw attention to the fact that more than one instance has been reported of deaths following an injection with more or less suddenness, which have been frankly accepted as due to the treatment, and not to the disease. 16. Paralytic sequelae. In our 1000 cases, and also in the 2848 treated in the Metro- politan Asylums' Board hospitals during 1893, paralyses were noted in 14 per cent, of the cases, and this is the exact number which occurred in the Series " A " and " B." The latter, however, includes 39 cases which have only been under treatment twenty-two days. In all of these the vital prognosis is favourable, but should a similar ratio of paralysis continue, the number in series "B" will exceed that in Series "A."* Baginsky remarked at Munich * No further deaths, but several more cases of paralysis (May 25, 1895). THE SERUM TREATMENT OF DIPHTHERIA. 261 that "paralysis is more frequent under antitoxin than before; perhaps because more children remain alive." If, as all are ready to admit, the serum acts most beneficially on that portion of the morbid influence which is due to the bacillus, as distinguished from those for which associated cocci are respon- sible, these results should be logically less frequent, rather than more so. 17. General well-being during treatment and convalescence. Some very roseate statements have been made as to the rapid and very marked and favourable change in the complexion, expression, and vigour which results from serum treatment. These we have not observed with such uniformity, or even frequency, as to justify the circumstance being claimed as a beneficial result of serum therapy. As to the later stages of recovery, any one who has visited diphtheria wards in which the serum treatment is used, cannot but be struck with the greater increase of pallor and listlessness on the part of the little patients than was formerly observed, even after the acute stages have been passed, and the throat is clear of membrane. This is in accordance with the statement of Sanarelli, who affirms that all injections of curative serum are followed by leucocytosis, which process, however, he believes lends support to the phagocytic theory, and to be there- fore beneficial. Mya has noted the same circumstance as the most obvious physiological, albeit transitory change in the blood which follows on a serum injection. While not appearing to adopt Sanarelli's deduction, he disagrees with the suggestion of Zagari, Calabrese, and others, that this is the result of any noxious action of anti- toxic serum, affirming that it is due solely to dilution of the blood caused by the injection of a heterogeneous serum, even in non-diphtherial cases. Nevertheless this globulicidal effect of seruni injections has attracted the special attention of our American confreres, who consider that it is a point quite over- looked by the founders of the treatment, German and French 262 APPENDIX. alike. Grabritchewsky and Morse, on the other hand, point out that leucocytosis is a normal phenomenon of reaction against diphtherial toxaemia. The truth is probably to be found at the crossway of all these various statements and opinions ; but whichever theory be correct, there can be but little doubt that, in respect of this as of other diphtherial process-changes, serum therapy does occasionally overshoot the mark. This we have seen to be the case in our comparative study of the clinical phenomena of the diseasa It is equally to be noted during convalescence. A greater number of children have been found liable to attacks of cyanosis and fainting, with a correspondingly increased demand for strong doses of nervine and alcoholic stimulants. Complete recovery is for the most part found to be greatly delayed, and an unexpected fatal result at a late period is more frequent. Conclusions. In our record of the clinical observations on this treatment, we have endeavoured impartially to reflect the experience of those Continental and home workers with whose results we are most familiar, and have recorded, with all reserve and deference, our own experience, whether it has agreed or disagreed with those conclusions. We nmst put it on the credit side of antitoxin that there is decided evidence outside our personal experience of diminished mortahty in infant Ufe ; and also of improved statistics with regard to intubation and tracheotomy. Our own observations record an improved mortality in nasal and laryngeal diphtheria, with a diminution in deaths from mechanical obstruction. In few of the returns has any statement been made — indeed, information on this point has even been suppressed— as to whether antitoxin was used as a substitute for all other treatment or as an adjuvant. The latter was the case in our series. The point is of importance from several aspects, both fro and con. When drawing attention at a meeting of the Clinical Society THE SERUM TREATMENT OF DIPHTHERIA. 263 last December to an increased liability to the most grave com- plications of diphtheria, viz., anuria, nephritis, and cardiac failure under the use of serum, we took occasion to express a hope that further experience might prove that the disadvantages of serum would be more than outweighed by its benefits. We deeply regret to be obliged to record facts which, if confirmed — and they are easily capable of being checked by parallel observations of others who may elect to make use of the opportunities which we have embraced — cannot fail to carry a contrary conviction. The ques- tion is, indeed, enforced on us as demanding an early reply, whether we are justified in continuing to pursue a treatment, the efficacy of which, in December 1894, seemed, in the opinion of the Clinical Society of London, "to be assured," but in which there is such a marked increase in some of the recognised complications of diphtheria, and the occurrence of several new ones of un- desirable, if not actually of fatal, significance. It may be that in some of the Continental hospitals, and even in those of our own city, where the mortality has hitherto been abnormally high, the results of serum therapy will be such as to suggest that the improvement is the direct outcome of the new remedy. But for reasons already stated, this reduced mortality may in a large measure be due to an amelioration of the personnel, which is the inseparable concomitant of all 'serum therapeutics, and by no means the legist important factor in the attainment of a lowered death rate. It is not unlikely that by a similarly increased observance of precautions against sepsis, the classical treatment will also in the future yield still better results. If further experiment be deemed necessary, the two methods should be offered parallel chances by treating in the same in- stitution each alternate patient by the one or other method respectively, with a careful comparison of the results. Whether the efficacy of the new treatment be finally accepted or disproved, we shall feel that we have accomplished a plain duty in reporting the foregoing facts as they have presented themselves 264 APPENDIX. during some months of close observation in an institution which has attained the premier position in regard to low mortality for some years past, by those methods of treatment known to us prior to the introduction of antitoxin. While correcting these pages we observe that Dr. Winters, of New York, has arrived at similar conclusions to ourselves on several of the points which we have considered. Employment of serum as a prophylactic. — The foregoing observations as to the effects of serum treatment will, we trust, have made it clear that the injection of antitoxic serum into a patient attacked by diphtheria is not altogether free from an added danger, notwithstanding that the amount of active principle administered can be measured only by millionth s ; and we have seen that the power of this serum to do good and iper contra its capacity for inflicting injury is in proportion to the duration of the disease — in other words, to the degree of the toxaemia. As a corollary, we might be able to pronounce that the power of antitoxic serum to act as a prophylactic against a possible attack of diphtheria is in proportion to the vigour and healthy blood condition of the individual in whom it is employed ; but the very minute dose administered for this purpose is evidently capable of being soon broken up by cellular action in the healthy. We can, therefore, understand the general admission as to the evanescent character of the immunity so obtained. Moreover, reports of cases are not wanting in which noxious and even fatal results have followed the use of serum when employed as a prophylactic. On all these grounds, therefore, we do not feel justified in recommending serum for this purpose. More real methods of preventing the spread of diphtheria are to be found in improved sanitation, in prophylactic surgical treat- ment already detailed, and in efficient isolation and disinfection. INDEX OF LITERARY REFERENCES. Abbott, Aetius, . Airy, . Aitken, Sir William, Albers, . Archer, . Aretseus, Arloing, Aronson, Asclepiades, 231 Baginsky, Baillou, Ballard, Bard, . Barthez, Benda, . Biddle, . Biggs, Hermann Billings, Biot, . Beale, Lionel, Beebe, Behring, Bergmann, Blaxall, Bleyer, . Bloebaum, Bokai, . Bosworth, Bouchut, Bretonneau, . 3, 4, 5, Brieger, British Medical Journal, Broadbent, Sir William, Brooks, . Buchner, Bulloch, Burrows, Sir George, Bury, Henry, Cadet de Gassicourt, Oalabrese, Carnall, Casselbury, Cattani, Chaillou, Cheyne, Watson, Cohn, Hermann, Corfield, Councilman, Cousins, Ward, 232. PAGE 43 4 . 19, 28 10 5 4 4 232 232 4 234 259, 260 4 28 4 183 257, 258 39, 40 44 182 151 7 210 233, 236, 239 228 28 201. 205 168 244 215 6, 7, 177, 200 . 65, 67, 185, 190 44, 58, 62, 232 229 10 8 231 62 9 17 185, 200 261 32 201, 206 231 45, 60 169 175 18 181 174 Daviot, . D'Espine, Deslandes, D'Hanvantare, Dieulafoy, Dobell, . Empis, . Esoherich, Evan Evans, Fagge, Hilton, Eerrein, Ferriar, Eox, Wilson, Fraenkel, . . 44, 58 Eraser, . Fuohs, . Etirst, Gabritchewsky, . * Gay ton. Gee, Glasgow Medical Jo^irnal, Goodall, Grant, Dundas, Grant, Taylor, Greenhow, Headlam, Gresswell, Guersant, '. Gull, Sir William, . Hamilton, Hankin, Hansemann, . Harley, Hayward, Hericourt, Herman, Heslop, Heubner, Hill, Hillier, . Home, Home, . Ingalls, . Jackson, Hughlings, .Taeobi, Jakins, . Jashura, Jenner, Sir William, Johnson, Sir George, Jurine, . PAGE 6 42 3 3 180 221 7 233 28 10 234 188 155 62, 182, 234 253 42 262 32, 99, 174, 195 154 177 45, 256, 259 186 . 53. 181 3, 7 28 5 . 41, 70 44, 58, 62, 232, 233 42, 256, 257 7 79 234 15, 17 32 40, 233 155 7 4, 84 28 201 157 . 3, 108, 131 177 232 7, 8, 33, 99, 149 27 5, 185 266 INDEX OF LITERARY REFERENCES. Kanthaok, . 62 Kelly, . .19 Kitasato, . 231, 232, 233 Klebs, 41, 42 Klebs-Loeffler, . . \ ct seq. Klein, . 48, 58, 64, 181, 238, 239, 254 Klemensiewicz, 233 Klemperer, . 233 Koch, . . 27, 41 Koplik, . . . 108 Kossel, . . 233 Kurth, . . 52 211. 229, 244, 256, 260 Lancet, 40, 45, Laycock, Leeuwenhoeck, Lefferts, Leo, Lepine, . Loeffler, ..15,41,42,74 Loiseau, Longstaff, Low, Bruce, . Maointyre, Mackenzie (Glasgow), . Mackenzie, Sir Morell, 3, 4, n, 92, Maguire, . . . . Marson, Martin, Louis, 45, 49, 60, 75, Martin, Sidney, '44, 58, 62, 65, Masselin, Medical Annual^ . Medical Press and Circular, . Metchnikoff, Meyer, P., Moizard, Morse, Murchison, Mya, Niemeyer, Noeard, Nuttal, . O'Dwyer, Oertel, 209, 229, Park, Parsons, Pasteur, Phillips, Leslie, Plant, . Poore, Vivian, Power, W. H., Prosskauer, . Pythagoras, . Kamsay, Rauohfuss, Raynaud, Renshaw, Richet, Ritter, Roberts, P., 41 177 232 255 170, '172, 209 6 13, 14, 18 28, 31 177 5 , 99, 156, 210 176 32 180, 251, 252 182, 233, 237 62 255 . 40, 45 230, 238 65 252, 253, 255 262 99 261 190 . 15, 235 231 . 6, 200 20, 182, 256 232 28 209, 210 28 41, 230, 231 86 52 27 28 62 3 19 3, 260 234 15,38 234 256 10 PAGE Roberts, Sir W., . . . . 225 Roe, . . . . ■ . . 201 Roux, 42, 43, 44, 51, 55, 58, 59, 60, 61, 62, 73, 74, 78, 122, 180, 210, 231, 233, 234, 235, 236, 239, 240, 244, 249, 251, 255 Ruault, . . 3, 60, 68, 182, 183, 185 Ruffer, . 60, 253, 254, 255 Ryland, .... 30 Salmon, Sanarelli, Sann^, . Saunderson, Burdon, Schech, . Schmorl, Schwalbe, Schwann, Siegert, Simon, Sir John, Smith, . Soerensen, Spear, Squire, Starr, Stern, Sternberg, Sweeting, Syme, Tanner, Thompson, Thoinot, Thome Thome, Thresh, . Thursfield, Tizzoni, Treymann, Trousseau, Variot, . Vincent, Virchow, Von Graefe, . Von Hoffman, Von Recklinghausen, Von Troeltsch, Wade, . Washboum, . Wassermann, Watson, Sir Thomas, Watson, William, Waxham, Weigert, Welch, . West, . Wheaton, White, Powell, . Wilks, . Wilson, . Winters, Woodhead, Sims, . Wright, Poyntz, . 6, 36, 37, 231 261 96, 177 7 . 87, 168 62 258 65 256 7, 32, 33 231 97 28 224 4 201 41 28 228 10 28,30 62 IS, 39, 56 . 40, 83 12, 13, 19 231 258 65, 67, 93 251, 252, 256 65 7, 36, 44, 228 7 42 44 172, 218 7 45, 256, 259 . 62, 232 7 177 200, 204 . 44, 183 43 7,30 28 79 7,9 31 264 55,83 16 Yersin, 42, 43, 44, 53, 55, 58, 59, 60, 61, 62, 73, 210 Zagari, ... . 261 GENERAL INDEX. As, unless oihcnoise stated, all details refer to "Diphthsbia, is not reiterated. this word Abscess at site of serum injeotion, 254 Abstract, tabular, of outbreaks, 1882-94, . . . 28, 29 Acid, lactic, in, 167, 169 ,, organic, of toxines of, . . 66 Adenitis in, . . 88, 89, 149, 254 „ suppurating, case of, . 149 Adenoid vegetations as a predis- ponent to, . 34 ,, ,, removal of, as a pro- phylactic, 214 ,, ,, removal of, during acute stage, 178 Advantage of laryngoscopy in de- ciding tracheotomy, . 194 ,, of laryngoscopy in diagnosis of croup, 185 ,, ,, in intuba- tion, 205 ,, ,, in treat- ment, 191 Age disposition to, ... 37, 144 ,, mortality in relation to, . 144 A.lbuminuria in, . 7, 90, 152, 255 Albumoses, action of, . 64 Alcohol in treatment of, . 162, 165 ,, ,, croup, 190 Algidity in, . . . 148 Anaesthesia in tracheotomy, . . 156 Anatomy, Morbid, of croup, . 179 „ „ of diphtheria, . 67 ,, ,, of pseudo-diph- theria, 72 Animals, domestic, in relation to, . 14 Antitoxic serum, as a prophylactic, 264 ,, disappearance of bacilli under, . . 251 „ dosage, . 239 , history of treatment by, . . . 230 ,, indications for em- ployment of, 239 PAGE Antitoxic serum, prefatory note, 228 „ „ preparation of, . 234 „ ,, results of treat- ment by, 242 ,, „ test of power of, 236 ,, „ theory of action of, . . . 237 „ „ treatment compared with classical, 243 ,, ,. ,, conclusions on, 262 „ ,, ,, convalescence after, . 261 „ , ,, weU-being during, . 261 „ ,, ,, skin eruptions caused by, 252 Anuria in, 152, 164, 256 Aphtha in relation to, . 98, 100, 101 Appendix, serum treatment of diph- theria (see Table of Contents, page xii.), 228 Articles of diet, formulae for, 225 Associates of diphtheria, . . 41 , , , , bacteriology of, 41 „ ,, in relation to virulence, 66 Asthenia in, 89 „ in croup, . 189 ,, treatment of, . 163, 165 Aural, complications in, 90, 94 ,, treatment of, 174 Bacilli, • disappearance of, under serum treatment, . 251 Bacillus coli, ..... 52 ,, of diphtheria, attenuated, 53 „ ,, description of, . 46 ,. ,, discovery of, 41 ,, ,, duration of activity of, 209 „ ,. identity of, . 42 „ ,, ,, arguments against, 43 268 GENERAL INDEX. Bacillus of diphtheria, identity of, grounds for, 42 „ „ in complex diphtheria (Fig. 21), 71 in situ (Fig. 20), 70 „ „ non-virulent, 53 „ „ toxic products of, 58 „ of pseudo-diphtheria, . 53 Bacteriological and clinical diagnosis, comparative table of, 82 , „ „ discrepan- cies in, 83 , , diagnosis of pseudo- diphtheria, . . 78, 79 ,, examination after recovery, 209 ,, diagnostic, 73 ,, prognosis in, . 137 Bacteriology of, . .41 Biot's respiration, 151 Bladder, paralysis of, 157 Bowel, ,, 157 Breath, contagion of , . 35 „ odour of, . . . 90 " Brisou" coccus, description of, 50, 78 ,, ,, diagnosis of, 78 ,, ,, in croup, . 180 Broncho-pneumonia in, . . . 89 ,, as a complica- tion of croup, 186 „ as a complica- tion after serum treatment, . 260 „ as chief cause of death after tracheotomy, 200 Bronchitis, as a complication of croup, 186 ,, pseudo-membranous, ,, 186 Buccal, site of membrane, . . -91 „ „ „ treatment in, 167 Calves, diphtheria of, . . 15 Canula, removal of, after tracheotomy, 199 Cardiac failure, . . 65, 89, 150, 259 „ „ treatment of, . 163 „ paralysis 157 Cardio-respiratory failure, . . 65 Case showing influence of prophylaxis, 1 7 ,, „ relation of measles to, 31 „ of non-bacillary croup, . 181 Cases of diphtheria of anus and vulva, 155 „ illustrative of country life in relation to, . . . 16 „ of bacillus of (1, 2, 3, 4), . 102 ,, „ with streptococcus (5, 6, 7, 8), . 110 ,, „ with streptococcus anddiploooccus (13), 120 „ „ with streptococcus and staphylococcus (9, 10, 11, 12), . 116 „ „ withdiplococcus(14), 123 „ diplocooous (22), . . 131 , „ and mycelium (23), 132 Case, indeterminate (24), . . 134 Cases, record of illustrative (Chap. VIII.), .... 102 „ staphylococcus (18, 19, 20), 127 „ „ and diplococcus (21), . 130 „ of streptococcus (15, 16), 124 ., ., and diplococcus (17), . 126 Casts, bronchial, in crou,p (Fig. 60), 186 ,, renal in diphtheria, . 90 Cause of, aggregation in school as a, 39 „ domestic surroundings as a, 22 „ infected milk as a, . 24 ,, geographical situation as a, 11 „ geological site as a, . , 18 Cfervical enlargement in, , . 90 Character of membrane in relation to prognosis, . . . . 145 Chemical composition of toxines of, 61 Chickenpox, in relation to, . 32, 100 Classification of microbes of, 81 Clay soil in, ... . 18 Climatic causes of diphtheria, . 11 Clinical and bacteriological diagnosis, comparative table of, . 82, 83 ,, description of membrane of, 92 ,, „ ,, pseudo-diphtheria, 95 ,, diagnosisof (Chapter VII.), 84 Cocci, associated, in relation to virulence, . Coccus " Brisou," Coli bacillus, Coma, toxic, .... Complications, after tracheotomy, „ aural, „ cardiac, . 65, 89, 150, 259 ,, laryngeal, . 153 „, neurosal, 156 „ renal, . . 152, 255 „ respiratory, . . 151 Concurrent epidemics in relation to, 30 Constitutional predisposition to, . Constrictors of pharynx, paralysis of, Contagion in, .... „ of breath in, Convalescence from, prophylaxis in, Convulsions in. Cough in, ... . Coverglass, diagnosis of, Croup(laryngo- tracheal diphtheria), (Chapter XI.), ,, abortive, ,, after-treatment of, 66 50,78 52 64, 152 200 90, 94 33 156 38 35 211 152 87 ,74 73 bronchial casts in, brush, .... canula, removal of, after tracheotomy for, casts, bronchial, in (Fig. 60); cause of death after tracheo- tomy for, . caustics in, . chloroform in, complications of, . cough in. 179 183 198 180 187 190 199 187 200 190 197 186 183 GENERAL INDEX. ■2h<) PAGE Croup, course of , . 186 „ descending, . 179 „ diagnosis of, 184 „ dyspnoea in, . 184 „ „ causes of, ' 185 „ emetics in, . 189 „ fatal issue, causes of , in, . 188 „ general therapeutic measures in, 189 „ hints for performing tracheo- tomy in, . . . . 196 „ intubation in, . . . 200 „ intubation compared with tracheotomy in, ■ . 191 ,, laryngoscopio signs of, , 185, 191 „ local measures in, . 190 ,, morbid anatomy of, . 183 „ non-bacillary (Fig. 59), . 180 „ case of, . . 181 „ morbid anatomy of, 183 „ operative measures in, . 191 „ pain in, . 184 ,, paralysis in, . . 186 „ prognosis in, . 186 „ removal of membrane after tracheotomy for, . 199 ,, sedatives in, 190 „ steam in, . . 188 „ symptoms of, . 183 ,, termination of, 186 tracheotomy in, . . . 194 „ ,, indications for, 194 „ „ mortality from, 195 ,, treatment of, general, . 188 local, . 190 „ ,, operative, 191 „ traumatic, . 182 Damp as a cause of, . 14 Death in, date and mode of, 158 Decayed teeth in relation to, . 36 Defects, sanitary, correction of, 216 ,, ., in relation to, 15, 16 Definition of croup, " 179 „ diphtheria, . 1 Diagnosis of, bacteriological,. 76 ,, clinical, . . 84 ,, croup, laryngoscopio, 185 „ by needle or streak cul- ture, . . 77 „ „ swab culture, . 77 Diaphragm, paralysis of, . 157 Diarrhoea in, . . . • 87, 152 Diet, articles of, formulae for, 225 .. iced, . .165 162, 165 206 199 30 1 23 11 27 18 3 26 „ m, . - „ after intubation, „ „ tracheotomy, Diphtheria, concurrent epidemics in relation to, . „ definition of, ,, drainage in relation to, „ etiology of (Chap. II.), ,, filth in relation to, geology of, . „ history of (Chap. I.), . „ importation of, . PAGE Diphtheria, intubation in, . . 6, 200 „ in relation to enteric, . 26, 98 „ „ measles, 26 ,, „ mumps, 100 rotheln, 100 ,, ,, scarlet fever, . 26, 96 „ „ sewer gas, 26 „ „ simple sore throat, 26,100 „ „ whooping- cough, 98 ,, of pigeons, . . . 15 „ preceding epidemics in relation to, . 30 „ school influence in, 18, 23, 26 ,, season, in relation to, 21 ,, tabular abstract of out- breaks, 1882-94, . 28, 29 „ tonsillotomy in, 6, 34, 213 „ tracheotomy in, . 6, 194 ,, tubage in, . 6, 200 Diplococous and mycelium, case of, 132 „ and staphylococcus, . 130 ,, and streptococcus, 126 ,, ,, case of, 126 ,, description of, . . 48 Disappearance of bacilli under serum treatment, . . 251 Disinfection during attack, . . 207 „ on termination of case, 215 Dissemination of, . . . 38 ,, by milk, 24 ,, by school influ- ence, . . 26, 39 Domestic animals in relation to diphtheria, ... 14 „ surroundings in relation to etiology, 22 „ „ in relation to prognosis, 144 Dysphagia in intubation, . 206 Dyspn ,, after tracheo- tomy, 199 ,, site of, a^ diagnostic. 91, 247 ,, solvents of prognostic, . 167 Membranous sore throat. Mercurial solutions in, . Methods of obtaining the toxines of. Micro-organisms associated with, . classification of, „ indeterminate, . ,, in pseudo-diphtheria Milk supply, infection of. 146 92 68 72 169 101 170 59 48 81 134 81 23 GENERAL INDEX. 271 PAGE Mixtures, formulae for, 219 Modes of death in. 158 Morbid anatomy of, . 67 Mortality, age in relation to prog- nosis, . 140, 244 245 „ in croup, 195 , , in relation to prognosis. 140 Mouth breathing in relation to, 33 Mumps in, . . . 100 Mycelium in, .... 52 „ and diploeocous, case of, 132 Narea anterior, as site, . 94 ,, posterior, . 94, 146 Nasal diphtheria, in relation to diag- nosis, . 88, 9^ „ in relation to prog- nosis, 146, 147, 236 ,, . treatment of, 173 Needle cultures, diagnosis by, 77 Neuritis segmental, . 66 Neuroses of, . . . 65 Non-baeillary croup, . . 180 ,, „ morbid anatomy of, . . 183 ,, „ case of, . 181 Non- virulent bacillus, . . . 1, 53 „ „ cases of, 109, 129 Nostrils, relative frequency of site, 91 Ocular, treatment of. Odour of breath in. Operation of intubation. Operative measures in croup, , , treatment in. Organic acid of toxines, Origin of. Otitis, .... ,, suppurative, Outbreaks, tabular abstracts (1882-94), Pain in back, in diagnosis of. Pallor in, under serum treatment. 162 of 175 90 201 191 176 66 14 89 255 28, 29 89, Paralyses in, . ,, facial, ,, in croup, , , intercostal, ,, laryngeal, ,, motor, , , ocular, . ,, oesophageal, , , of bladder, ,, of bowel, ,, of constrictors, ,, of diaphragm, ,, pharyngeal, . , , reflex, ,, sensory, . , , toxic, ,, visceral, Parotid, glandular enlargement of. Pathology of, ... Perchloride of iron in, . PAGE Personnel of, in prognosis, . 139 „ in prophylaxis, . . 207 „ in treatment, . 160, 229 Polluted vi^ater in, etiology of, . 14 Post-nasal diphtheria, treatment of, 173 Prognosis, elements of (Chapter IX), 136 „ bacteriological, . 137 „ clinical, . 145 Prophylaxis by uvulotomy, . 214 ., by surgical treatment, 213 ,, tonsillotomy, 213 Pseudo-diphtheria, . . 1 „ bacillus, . 53 „ bacteriological diagnosis of, 78, 79 „ clinical diag- nosis of, . 95 „ morbid anatomy of, . . 72 ,, treatment of, . 163 Rainfall as a cause of, . 19 Record of illustrative cases, 102 Rectum, paralysis of , . . ] 57 Relation of, to damp, 14 ,, polluted water, . 14 Remedies, formulae for (Chap. XIII. ), 217 „ internal, in, 161 „ topical, in, 162 Removal of adenoids as ", prophy- lactic in, . 214 ,, „ as treatment of , 178 intubation tube, . 204 ,, membrane, . 169 ,, ,, after tracheo- tomy, 199 ,, tonsils as a prophy- lactic in, ,, ,, as treatment of. ,, ,, hints on, . ,, „ case of. Renal complications, . . 90, 261 156, '260 156 186 157 156 157 156 156 157 157 156 157 156 157 157 64 157 90 67 168 Reports, tabular abstracts on out- breaks of. Respiratory complications. Rhinitis hypertrophic, in relation to preventive surgical treatment, Rigors in, . . . Rotheln in relation to, 213 176 213 176 152, 255 28, 29 151 214 87, 149 100 Scarlet fever in relation to, 26, 30, 31, 33, 96 School influence „ 18, 23, 26, 39 Season ,, . . 21 Segmental neuritis in, . . . 66 Serum, antitoxic {see Antitoxic Serum). Sewerage in relation to, 23 Sewer gas „ . . 27 Simple sore throat „ . 100 Site of membrane in diagnosis of, . 91 Skin eruptions in, . . . . 88 „ ,, after serum injections, 251 Smallpox in relation to, 31, 99 Smell, perversion of, . 90 Soil, ... 18 Solvents of membrane, 167 272 GENERAL INDEX. PAGE Specific causes of, ... 11 Spiroohoeta, a cause of pseudo-diph- theria, ..... 52 Stables, defects in, as a cause of, . 15 Staphylococcus, cases of, . 124 ,, ,, diagnosis of, 78 diagnosis of, . . 60 „ varieties of, 52 Stridor in, . . . 87, 153 Subdivisions of, . . 44 Swab, culture of, . . 77 Syringe in, 171 System, general influence on, . 68 Taste, perversion of, . . 90 Temperature in, . . . . 88, 251 Termination of case, disinfection on, 209 ,, croup, . . 186-188 Time for performing tracheotomy in croup, . 196 Tongue in 87 Tonsils, removal of, as a method of treatment, . 176 ,, „ as a preventive measure, 213 „ ,j case of. . 176 , , as a site of membrane, 92 , , hypertrophied in, . 33 Topical measures in croup, . 190 ,, „ diphtheria, . 190 Toxaamia of, 64 Toxine, organic acid form, . 66 Tracheotomy, compared with intuba- tion, ... 191 ,, cause of death after, 200 „ in croup, . . . 194 ,, removal of canula after, . 199 Traumatic croup, .... 182 Treatment of (Chapter X.), . . 160 , , after intubation, . 206 ,, of croup, . .188 ,, of pseudo-diphtheria, . 163 „ operative, . . 162 Turbinals as site of, . . 94 Uraemia, . ... 152 Urea, excess in, ' . . 90, 255 Urine in. . . . 90, 152, 164, 256 Uvula in, . ... 88 Uvulotomy in acute stage, , 176 in prophylaxis, . 214 Vapour in croup, . . . . 189 Virulence as influenced by associ- ated cocci, .... 67 Visceral paralysis in, . . . 157 Voice, change in, result of paralysis, 156 „ in croup, . . 184 ,, in diphtheria, . 87 Vomiting in, . , . . 87, 152 Water, polluted, in, etiology of, . 14 Whooping cough in relation to, . 98