Diptheria, its nature and treatment

Preface

I have been emboldened to offer the present work to the Profession by the many gratifying- assurances which I have received that my previous writings, which appeared in 1876 and at several subsequent times, have been of service to some. Those writings consisted mainly in statements of my own clinical observations and experience. My chief motive in adding* the present one has been a desire to express my views on various important points somewhat more fully than was possible in them, and in connection with related facts in the history, the etiology, and the pathology of the disease, and recent advances in its therapeutics.

To have made this an exhaustive treatise would have been impossible, in view of the great variety of aspects which have been assumed by the disease and its complications in occasional epidemics and individual cases, the wide diversity of the views which have been entertained as to its pathology, and of agents and methods which have been employed in its treatment, the resulting vastness of the literature relating to it, and the limitations of the time and space at my disposal. I have, however, endeavored to present a clear and succinct statement of those facts in existing knowledge which are most essential to the formation of an intelligent opinion as to its nature, and of those therapeutical principles and details, the

IV PREFACE.

comprehension and application of which will, as I believe, enable the physician to treat it most successfully.

It affords me much pleasure that Dr. O'Dwyer has kindly consented to treat, in this connection, of that very important addition made by him to our therapeutical resources in dealing- with the most distressing- and fatal form of diphtheria, — intubation of the larynx.

C. E. BlLLINGTON.

New York, April 15, 1889

Etiology 259

INTUBATION IN CROUP

And other Acute and Chronic Forms of Stenosis of the Larynx 265

DIPHTHERIA;

ITS NATURE AND TREATMENT.

Chapter I. Definition And History

Diphtheria is a specific disease which occurs sporadically, endemically and epidemically, and is contagious and infectious, its essential characteristic being an inflammation of mucous membranes, or of the surface of wounds and the adjoining integument, which tends, by cellular proliferation and degeneration and by fibrinous exudation, to the formation of a false membrane, and also to the production of a poison which, when absorbed into the circulation, causes morbid changes in the blood and in various organs of the body.

The name diphtheria was first suggested by Bretonneau,

who in his earlier publications employed the term diphtherite,

derived from the Greek dt<pdapa, a membrane, the termination

ite (err}?) signifying inflammation, and the compound word

thus admirably describing the " specific phlegmasia" which

constitutes the local affection; but in his fifth memoir he

adopted instead from Trousseau the name diphtherie, which,

without the limiting suffix, more fitly designates the entire

disease with its train of local and constitutional phenomena.

The equivalent name, diphtheria, was thence adopted by Dr.

W. Farr, .Register General of England, and has since been

universally employed by writers in the English language. 1

Although this name and much of the more exact knowledge of the disease which has accompanied and followed its introduction are of recent origin, there is abundant evidence that the malady itself has prevailed widely among mankind since the most ancient times. In the sixth century B.C. or thereabouts, D'havantare, an Indian physician, in his " System of Medicine," written in Sanskrit, described the symptoms of an incurable disease called " closing of the throat," and " arising from phlegm combined with blood," which could hardly have been other than diphtheria. 1 The assertion, which has been made by some, that the disease is referred to in the Hippocratic writings, 2 rests on very inconclusive evidence. Asclepiades, in the first century B.C., is said to have performed laryngotomy. Aretaeus of Cappadocia, in the first century a.d., gives a graphic and unmistakable description of faucial and laryngeal diphtheria under the names ulcera JEgyptiaca and ulcera Syriaca, which are significant of its wide prevalence. He says that " some ulcers on ths tonsils are mild and others are pestilential and deadly." The latter are " extensive, deep, putrid and coated with white, livid or black concretions." He then describes the development and extension of this form of the disease in the throat and the mouth and as a phlegmon on the neck, and its fatal result in "not many days," and adds, " But if this malady invades the chest through the windpipe, it causes suffocation on the same day." He then vividly depicts the symptoms and the struggles which are too often witnessed in the later stages of a fatal case of diphtheritic croup and completes the nosological picture by adding, " Children up to the age of puberty are chiefly affected by this disease." 3 Galen probably referred to diphtheria when he mentioned the expectoration of false membrane from the

'Quoted in "Diphtheria, its Nature and Treatment," by Morell Mackenzie, M.D., p. 14.

2 Hippocrates : "de Epidemicis," lib. v. cap. iv., and "de Dentitione." 3 Aretaeus: " De Causis et Signis Acutoruni Morborum," lib. 1 cap. 9.

pharynx ana the air-passages. 1 Coelius Aurelianus in the third century depicted the symptoms of diphtheritic laryngitis and also mentioned the imperfect articulation and the regurgitation of liquids through the nose in swallowing, which result from diphtheritic faucial paralysis. 2 Aetius of Amida in the fifth century described a disease of children, in which the whitish and grayish faucial appearances, the dysphagia, the suffocation, the characteristic symptoms of resulting palatal paralysis, sudden death after apparent recovery, and intolerance of too harsh local treatment form a complete clinical picture of diphtheria. 3 The probability, from some passages in the historians, that severe epidemics of this disease may have occurred in antiquity, of which we have no record by medical writers, is illustrated by Bretonneau (second memoir) in the instance that Macrobius in the year 380 a.d. speaks, according to Julius Modestus, of sacrifices which were instituted in honor of a heathen goddess, " ut populus Romanus morbo qui Angina dicitur, promisso voto, sit liberatus."

For an interval of more than a thousand years, which constituted the " Dark Ages/' there is no distinct record of the disease, probably not from its non-occurrence, but from a lack of competent observers. It is with good reason supposed that some of the "plagues" of the Middle Ages may have been epidemics of diphtheria. Among these were the pest called " esquinancie," a form of angina maligna mentioned in the chronicle of St. Denis for the year 580, and a destructive "pestilentia faucium " at Rome in 856, and another in 1004 recorded by Baronius, and a fatal " cynanche " in the Byzantine empire in 1037 recorded by Cedrenus, and an angina which carried off many children in England in 1389, referred to by Short. 4

In the sixteenth century records of the occurrence of epi-

! "De Locis Affectis," lib. 1. cap. 9.

8 "D'e Acutis Morbis," lib. iii., cap. 2 et cap. iv.

3 Petrabibl. Sermo viii. , cap. 46.

4 Cited by Hirsch, Geog. and Hist. Pathol., vol. iii.

4 DIPHTHEEIA; ITS NATURE AND TREATMENT.

demies of diphtheria beg-in rapidly to multiply. Among- these an epidemic in Holland in 1557 was described by Peter Forest l as an " angina malig-na contagiosa," rapidly fatal b}^ strangulation, and another in 1564 and 1576 mentioned by Van Wier 2 as an " angina maligna," particularly common among children and fatal in from one to seven days; others occurred in the Rhenish provinces and in North Germany, and one in Naples and Sicily. An epidemic in Paris in 1576 was described by Baillou, 3 who mentioned false membrane as observed in an autopsy: " Pituita lenta contumax quae instar membranae cujusdam arteriae asperse erat obtenta."

In Spain a great epidemic, or succession of epidemics, of angina maligna, there known under the popular name of gar rotillo, raged from 1583 to 1618, and was well described by a number of medical writers. Beginning in Seville in the former year, it reached its widest diffusion over the country about 1610, and in 1613 the mortality was so frightful that that year has since borne the name of "anno de los garrotillos." Among the best descriptions of the disease were that of Villa Real, 4 who minutely described false membrane as seen by him, not only in many cases during life, but also in autopsies; that of Herrera, 5 who also observed diphtheritic false membrane in autopsies, and described diphtheria of the skin and of wounds ; that of Mercado, 6 physician to Philip II. and Philip III., who noted the slight degree of fever present in some very grave cases, described diphtheritic cervical adenitis, and mentioned an instance of a child communicating the disease to its father

2 Van Wier : Observat. lib. i, sec. 3.

3 Epidenriorurn, lib. ii., Genev. 1762.

4 Villa Real : " De Signis Causis, Essentia, Prognostico et Curatione Morbi Suffocantis," Compluti 1611.

6 Consult, med. lib. cons, xiv., in opp. Frankf. 1620.

by biting- his finger; and of Heredia, 1 physician to Philip IV., who distinguished the two forms of the disease, the suffocative and the asthenic, observed paralysis of the palate, the pharynx and the limbs, believed in a secondary infection by the resorption of morbid products, and recommended for its prevention the early employment of cauterization.

An epidemic in Portugal in 1626 is described by Barbosa. 2

In Italy malignant sore throat, having been prevalent in Mantua and Lombardy in 1610, 3 broke out in the city of Naples in 1617, gradually overran the kingdom of the Two Sicilies and the States of the Church, and prevailed in various epidemics and recurrences in many parts of Italy until 1650. Among the accounts of these epidemics are that of Sgambatus, 4 Carnevale, 5 Aetius Cletus, 6 who vividly described not only pseudo-membrane in the fauces, but the gangrenous, the laryngeal, the toxgemic, the asthenic, and the nasal forms of the disease, and also the protracted debility and the paralysis of the vocal organs of those who recovered; and Severino, 7 who described diphtheritic membrane as seen in an autopsy, and diphtherial paralysis.

In the eighteenth century angina maligna was even more prevalent than in the seventeenth, occurring in nearly every country of Europe and in some portions of America. Many localities in Spain and Portugal were invaded by it between the years 1701 and 1786. It prevailed in Paris and in many other towns in France in 1743-50; again in Paris in 1758-9 and in 1762. The first of these epidemics was described by Marteau

5 " De Epidemico Strangulators Affectu," etc. Neapoli, 1620. 6 " De Morbo Strangulators opus." Romse, 1636. 7 " De Pedauchone Maligna," etc. Neapoli, 1643.

ITS NATUEE AND TREATMENT.

de Grandvilliers, 1 and by Chomel, 2 who accurately described paralysis of the soft palate, and a case of diphtheritic strabismus. Epidemics occurred in various portions of Italy between 1747 and 1786. One which prevailed in Palermo in 1747-8 was described by Ghisi, 3 who observed laryngeal croup and pharyngeal angina gangrenosa as each occurred separately, and when both were united in the same patient, and noted the phenomena of diphtheritic paralysis. Epidemic outbreaks occurred in Holland between 1745 and 1770. In Great Britain an epidemic of angina maligna, was described in 1713 by Dr. Patrick Blair, 4 under the name of "the croops" as "universal" at Coupar Angus. In 1748 a fatal outbreak in London of scarlatina anginosa, which was complicated with diphtheria, was described by Dr. Fothergill. 5 In 1745-8 a "morbus strangulatorius," which presented the characteristic features of malignant diphtheria, prevailed in Cornwall, and was described by Starr. 6

In 1765 appeared the treatise on croup by Francis Home of Scotland. 7 This work is very important, not only from the completeness of its descriptions and the logical force of its deductions, but also from the fact that it, for the first time, clearly depicts a form of pseudo-membranous disease which was regarded by him and has since been regarded by many others as distinct from diphtheritic angina. According to him croup, or, as he names it, " suffocatio stridula," is a disease which " belongs peculiarly to children." It " has a local

1 " Dissertation Historique sur l'espece de Mai de Gorge Gangr6neux qui a i'6gn6 parmi les Enfants Fannie derniere." Paris, 1749.

2 "Dissert. Hist, sur l'aspect du Mai de Gorge Gangr6neux, " etc., Paris, 1749.

4 " Observations in the Practice of Physic," etc. London, 1713.

5 "An Account of the Sore Throat Attended with Ulcers," by Dr. John Fothergill. London, 1748.

6 " Philosophical Transactions," 1750, t. xlvi., p. 435.

7 "An Inquiry into the Nature, Causes and Cure of Croup," by Francis Home, M.D. Edinburgh, 1765.

DEFINITION AND HISTOEY. 7

situation," being- "seldom found at any great distance from the sea-shore/' though " very wet and marshy situations sometimes produce it." Its occurrence is also favored by cold and damp weather, and recent attacks of measles, whooping-cough or small-pox predispose to it. It is "a disease of an inflammatory nature," which " appears to be confined chiefly to the trachea, as the patients have no pain in deglutition, and as the fauces are at most but a little redder." " The place first and most particularly affected is the upper part of the trachea, about an inch below the glottis." " The cause of this disease is a preternatural white, tough, thick membranous crust covering often for many inches the inside of the trachea." " This membrane is not attached to the parts below, but is easily separated from them, as there is always matter behind it." There are two forms of the disease, " the inflammatory and less dangerous, and the less inflammatory and highly danger - ous." This description is based on twelve cases, of which three were of the former or catarrhal variety, and terminated in recovery, and are given as examples of those which are "common." The other nine were fatal ones, and in all of these autopsies were made, the membrane as above described being found in every one. In only one, which he regarded as complicated with " angina," the throat and tonsils were inflamed and " covered with mucus." There is no mention of an epidemic character nor of contagiousness in the disease described, but it is possibly worthy of note that two of the fatal cases (IV. and V.) were those of a brother and sister, the former having been attacked September 29th, 1760, the latter, October 5th. The treatment he advises consists of blood-letting, blisters, emollient fomentations and cataplasms around the neck, inhalation of the steam of water and vinegar, and gentle sudorifics. Emetics he had not found useful. When the membrane has formed he recommends bronchotomy.

Diphtheria again prevailed in London and in some other localities in England in 1790-1793.

Epidemics occurred in Germany in 1752, 1755 and 1790. In 1778 Michaelis 1 in Gottingen wrote in confirmation of the descriptions and views of Home. The disease prevailed in the Simmenthal, Switzerland, in 1752, and in many places in Sweden in the years 1755-62. In the latter country Wilcke in 1757 described pseudo-membranous angina. 2

In New England an epidemic occurred in 1735, which was described by Dr. William Doug-las 3 as originating in Kingston township, about fifty miles eastward of Boston, and after prevailing with great fatality in the surrounding country, at length reaching Boston, where it was much milder. The symptoms of this malady, which are fully detailed, are clearly those of scarlatina, but in many instances there was evidently a complicating or secondary diphtheria.

Two years later a similar epidemic is described in a letter from Eev. J. Dickinson, 4 dated " Elizabeth Town, New Jersey, February 20, 1738-9," as having occurred in that place some time previously, a portion of which description is so vivid as to be worthy of quotation. He describes the disease in six forms, the first being evidently scarlatina, or possibly in some cases measles. The second form " frequently begins with a slight indisposition, much resembling an ordinary cold, with a listless habit, a slow and scarce discernible fever, some soreness of the throat and tumefaction of the tonsils; and perhaps a running of the nose, the countenance pale and the eyes dull and heavy. The patient is not confined, nor any danger a/p-

2 "Diss. Med. de Angina Infantum." Upsala, 1764.

3 "The Practical History of a New Epidemical Eruptive Miliary Fever with an Angina Ulcusculosa which prevailed in Boston, New England, in the years 1735 and 1736. Printed and Sold by Thomas Fleet.

4 " Observations on that Terrible Disease, Vulgarly called the Throat- Distemper, with Advices as to the Method of Cure." In a Letter to a Friend. By J. Dickinson, A.M. Boston: Printed and Sold by S. Kneeland and T. Green in Queenstreet over against the Prison, 1740." Jonathan Dickinson was the first President of Princeton College and the first pastor of the Presbyterian church of Elizabeth, N. J.

prehended for some days, until the fever gradually increases, the whole throat and sometimes the roof of the mouth and nostrils are covered with a cankerous crust, which corrodes the contiguous parts and frequently terminates in a mortal gangrene. When the lungs are thus affected the patient is first afflicted with a dry, hollow cough, which is quickly succeeded with an extraordinary hoarseness and total loss of the voice, with the most distressing asthmatic symptoms and difficulty of breathing, under which the poor miserable creature struggles until released by a perfect suffocation or stoppage of breath. This last has been the fatal symptom under which the most have sunk that have died in these parts. All that I have seen to get over this dreadful symptom have by their perpetual cough expectorated incredible quantities of a tough whitish slough from their lungs."

Dr. Cadwallader Colden 1 traces the progress of the epidemic from Kingston westward, it appearing " first in those places where the people of New England chiefly resorted for trade, and in the places through which they travelled " until it "spread over all the British colonies in the Continent," "children and young people" being "only subject to it; " but he adds nothing of importance to the two descriptions of the disease just quoted.

In 1771 appeared the classical treatise of Dr. Samuel Bard 2 of New York, who described with clearness and accuracy pharyngeal, laryngeal and cutaneous diphtheria, occurring separately and in the same patients, from clinical observation

1 " Extract of Letter from Cadwallader Colden, Esq., to Dr. Fothergill concerning the Throat Distemper," dated Coldenham in New York, 1753. Published in London Observations and Inquiries, vol. i., p. 211.

2 "An Enquiry into the Nature, Cause and Cure of the Angina Suffocativa or Sore-Throat Distemper as it is commonly called by the Inhabitants of this City and Colony. By Samuel Bard, M.D., and Professor of Medicine in King's College, New York. Printed by S. Inslee and A. Car, at the New Printing-Office in Beaver Street, MDCCLXXI." Reprinted in Transactions of the American Philosophical Society, Philadelphia, 1789.

and post-mortem examination, as pseudo-membranous but not gangrenous affections, and believed that these various forms of disease, with those described by the Italian writers and by Home, Fothergill, Huxham and Douglas, were essentially related and "arise from the same leaven. " He also described consecutive paralysis affecting deglutition, speech and locomotion, and emphasized the infectiousness of the disease and the importance of isolating the sick.

Although the masterpiece of Bard has in recent times been appreciated at its true value, it does not seem to have commanded the contemporaneous attention which it merited, and the ideas of Home maintained their ascendancy.

Their influence is illustrated in a "letter on the croup " from P. Middleton, 1 M.D., to Mr. Richard Bayley, surgeon, New York, dated New York, November 30, 1780. He says, "When I first came (from Scotland) to this city in 1752,1 found complaints of the throat not infrequent, but most of them were usually considered as having a malignant tendency if not actually anginse gangrenosa?, and in consequence of this general belief antiseptics were the remedies used in preference to all evacuants except perhaps emetics." He proceeds to state his belief that croup is " totally distinct from malignant sore throat/' and asserts that though the two affections may be united, he has never seen such an instance.

Similar views appear in a letter on the croup from Professor Richard Bayley 2 to William Hunter, M.D., London, published about 1781. He quotes with approval the post-mortem observations of Bard, but regards angina trachealis as an " inflammatory " affection, and, like Dr. Middleton, has treated it successfully, even in its advanced stages, by the vigorous employment of venesection, blisters, mercurial evacuants and emetics.

Dr. John Archer, 3 in a letter to Benjamin Smith Barton,

1 Medical Repository, New York, vol. xiv., p. 347.

2 Medical Repository, New York, vol. xii., p. 331, and vol. xiv., p. 345. 8 Medical Repository, New York, vol. ii. p. 27.

M.D., of Philadelphia, dated Hartford County, Maryland, March 17, 1798, likewise considers croup as a "topical disease, confined to the trachea arteria, and the several ramifications thereof/'

In France, also, at this period most writers held the same views regarding" the distinct nature of croup and angina maligna.

Several members of the imperial family having died of the former disease, a prize was offered by Napoleon I. for the best essay upon it. This prize was divided between Jurine, of Geneva, and Albers, of Bremen. Jurine recognized the fact of the frequent concurrence of croup with angina gangrenosa, and expressed doubt as to the actual existence of gangrene in the majority of cases of the latter disease.

At length appeared the writings of Bretonneau, which may be said to have founded on a firm and broad basis the modern knowledge of diphtheria. Many of the facts which he announced respecting the disease had, as we have seen, been previously observed and stated by others. It was his glorious achievement to establish them by incontrovertible demonstration and to present them in their true relations. The principal writings of Bretonneau x consist of five papers or memoirs, the first two of which were read at the Academie Royale de Medecine in 1821 ; the last was published in 1855. His studies of the disease were principally made in three great epidemics, that of Tours in 1818, de la Ferriere in 1825, and Chenusson in 1826. The most distinctive feature of Bretonneau's work was the great amount of necroscopic research which it comprised, sixty autopsies being referred to in the first epidemic alone. Among the most important points established by his observations were the absence of gangrene in most cases of diphtheria,

1 " Des inflammations speciales du tissu muqueux et en particulier de la diphtbeYite, ou inflammation pelliculaire connue sous le nom de croup, d'angine maligne, d'angine gangreneuse, etc., Paris, 1826.'" " Sur les moyens de prevenir le developpement et les progres de la diphtheric " Archives Grenerales de M6decine, 1855.

the nature and the relations of pseudo-membrane, its frequent continuity and its essential unity in the buccal, the naso-pharyngeal and the laryngotracheal regions, the specificity of the diphtheritic inflammation in distinction from the catarrhal and from other specific phlegmasia, the non-identity of membranous and "spasmodic" croup, and the true relation of sequence and causation between the local and the constitutional phenomena of diphtheria, which he expressed in the phrases, " localized primitive diphtheria " and " the secondary or constitutional affection." x

The teachings of Bretonneau were ably seconded and amplified by various writers, among the earliest of whom were Guersant, 2 Louis, 3 Gendron 4 and Mackenzie, 5 the two latter of whom were among the earliest advocates of the topical use of nitrate of silver.

During the earlier half of the present century the prevalence of diphtheria greatly diminished, except in France where numerous epidemics occurred between 1810 and 1843, and again from 1816 to 1855. In other European countries and on this continent it was either unknown or occurred only sporadically or in occasional and limited epidemics. In 1856, an outbreak having occurred at Boulogne, in France, which was especially fatal among the resident English, the disease was conveyed to England and prevailed there in numerous and fatal epidemics until 1863. At about the same time a new and more general outbreak than had ever before occurred began not only in Europe and America, but also in Asia, Africa, Australia and Polynesia; and that general prevalence of the disease has since continued, though often in a greatly

1 Fifth Memoir.

2 Dictionnaire de Medecine, Articles "Angine Couenneuse," t. ii., " Croup," t. vi., and " Stomatite Couenneuse," t. xix.

3 " Du Croup consider^ chez ladulte," Arch. Gen., t. iv., pp. 1 and 369.

4 " Observations sur une Angine Couenneuse," Journal Compl^mentaire du Diction, des Sciences Med., t. xxiii., p. 346.

5 "On the Symptoms and Cure of Croup," Edin. Med. and Surg. Journ., vol. xxiii., p. 294.

DEFINITION AND HISTOKY. 13

mitigated form, until the present time, so that in most of the cities of the world at the present day diphtheria contributes a considerable annual quota to the list of mortality.

Under these circumstances it is not surprising- that the literature of the disease has assumed enormous proportions, and is less and less occupied with accounts of particular epidemics and more and more with questions relating to etiology, pathology, and therapeutics.

As various writers will necessarily be referred to in the chapters on these subjects, but few additional ones need now be enumerated. Deslandes, in 1827, 1 in considering the question of the identity of pseudo-membranous angina and croup, gave a minute and valuable historical review of the subject of epidemic sore throat. His views on the question referred to accord affirmatively with those of Bretonneau. The doctrine that diphtheria is a primarily constitutional affection was advocated by Emangard, 2 who attacked the views of Breton neau from the point of view of the "physiological" school, maintaining that the disease is of malarial origin and of kindred nature to typhus — a " gastro-enteric angina." Fuchs 3 also, after a historical review of the subject, held that angina maligna was a " typhus " identical with the pulpous form of hospital gangrene.

Both of these questions, namely that of the identity or diversity of membranous croup and diphtheria and that of the primarily local or constitutional nature of diphtheria, have since been discussed by many waiters from opposite points of view, representing a diversity of opinion which continues to the present day.

Trousseau, 4 the friend and pupil of Bretonneau, was his

Journal des Progres des Sc. Med., t. i., p. 152.

2 " Examen Critique du Traite" de la Diphtherie par M. Bretonneau." Paris, 1829.

4 "Memoir sur une epidemie d'Angine Couenneuse Scarlatineuse, "

worthy continuator, and supplemented his work by addingfrom 1829 to 1858 observations which were necessary to the complete description of diphtheria, especially in reference to its cutaneous form and its constitutional manifestations, including- albuminuria and the various forms of resultant paralysis. Trousseau was, moreover, like Bretonneau, a warm advocate of tracheotomy, and devoted much attention to perfecting- its method and details. The statement of Bretonneau that diphtheria is never accompanied by true gangrene, was shown to be subject to many exceptions by Trousseau and also by Becquerel, 1 Rilliet and Barthez, 2 and Simon. 3

The occurrence of albuminuria in connection with diphtheria was first discovered in 1857 by Dr. W. F. Wade, 4 of Birmingham, and was soon after independently observed by Dr. Germain See, of Paris. 5

Diphtheritic conjunctivitis was first elaborately treated of by Yon Graefe 6 in 1857. His publication was closely followed by that of Prichard. 7

The first important publication on the subject of diphtheritic paralysis was that of Maingault. 8

The first precise description of the anatomical distinctions between the different forms of inflammation of mucous membranes by Yirchow in 1847, and the first announcement of the discovery of a supposed bacterial cause of diphtheria by Lay- Arch. Gen., t. xxi., p. 541 ; " De la Diphtherite Cutanee," ibid., t. xxiii., p. 383; " Lecons Cliniques sur les Angines," Gaz. des Hop., Nos. 86, 89, 100, 104, 109, 115, 119, etc.

^'Relation d'une Epid6mie d' Affections Pseudo-membraneuses et Gangr6neuses qui a regne a l'Hopital des Enfants," Gaz. Med., Nos. 43, 44, 45, 46.

2 " Maladies des Enfants," t. i., pp. 285, 316.

3 Considerations sur l'Angine Gangreneuse et de son traitement, " Bull, de Therap., t. xxiv., p. 401.

4 Midland Quarterly Journal of the Medical Sciences, April, 1858.

5 Union M<5dicale, 1858, p. 497. 6 Archiv. f. Ophthal., b. 1, s. 168. 'British Med. Journ., 1857, p. 981. 8 These de Paris, 1854.

cock in 1858, and many important subsequent pathological and etiological investigations by others, will be more appropriately referred to elsewhere in this work.

In treatment, hydrochloric acid, alum, and later nitrate of silver, were locally employed by Bretonneau, and in some cases mercury internally. Tonics were advocated by Becquerel 1 in 1843; alkaline treatment by Baron 2 in 1851; chlorate of potassa by A. Smith 3 in 1855; iodine by Lecointe, 4 and bromine by Ozanam 5 in 1856; muriated tincture of iron internally by Heslop in 1858 ; 6 iron and chlorate of potassa by Kingsford; 7 sulphur by Duche 8 in the same year, and turpentine by Perry 9 in 1859.

A method of intubation of the larynx having been devised and warmly advocated by Bouchut, a report on the subject was presented to the Academie de Medecine by Trousseau in 1858, so unfavorable that the procedure was condemned by the general verdict of professional opinion, was abandoned by its author, and fell into such oblivion that when Dr. Joseph O'Dwyer, of New York, a quarter of a century later, invented and perfected the method of intubation which has rapidly won acceptance among the great therapeutical improvements of the age, he did so in ignorance of the fact that his idea had been anticipated.