Aphthae and Diphtheria THEIR ASSOCIATION AND DIFFERENTIATION BY ADOLPH RUPP, M.D. New York. RRPRINTBD FROM The American Journal of Obstetrics Vol. XXIX. No. 2,1804. NEW YORK WILLIAM WOOD A COMPANY, PUBLISHERS 1894 APHTHAE AND DIPHTHERIA. THEIR ASSOCIATION AND DIFFERENTIATION.1 The object of this paper is to call attention to the fact that although most if not all our textbooks scarcely comment on the association of aphthae and diphtheria, these diseases do occur " side by side " or concurrently ; and, secondly, although typical manifestations of aphthae can hardly be mistaken for diphtheria, even after a hurried or superficial examination, in most cases, occasions are not wanting when the mistake may be made by tolerably careful observers ; and, lastly, when the two diseases coexist in the same patient, aphthae may manifest themselves before the symptoms and signs of diphtheria have done so, and thus the benign malady will more or less mask the serious dis- ease. This last fact is not even hinted at by most writers on both diseases, and, although a contingency of not common oc- currence, it is of enough importance to be borne in mind. I. From the days of Hippocrates down to our own, confusing conceptions as to what should be understood by the term aphthae have been taught by representative authors. Taking the mildness of the malady as it is usually met with into ac- count, along with its accessibility for observation and study, one is at first surprised at this; but the mildness of any disease and its accessibility for study and observation are not always the factors that stimulate most effectually toward getting at its secret or essential characteristics. To discuss and enumerate the factors which have influenced the study and developed the various conceptions of aphthae at the different epochs of its his- tory is not the object of this paper. But so much of the his- tory of these two diseases may be reviewed as will help us to 1 Read at the January meeting of the Northern Dispensary Medical Society, 1894. 2 RUPP : APHTH.E AND DIPHTHERIA. form a clearer conception of the meaning of this frequently almost insignificant malady-aphthae. And though it may be interesting enough and hardly exhilarating, some food for mod- est reflection will fall in our way as we go along. Bohn states that the confusion begins with Hippocrates ; and Galen, who taught five hundred years later, added nothing to the knowledge of the trouble, but left the confusion greater. Indeed, some of this old-time confusion continues into our own day. Billard,1 who is praised justly and a good deal by Bohn for having brought the conception of aphthae within definite clinical limits, writes of those who taught before him as fol- lows: "The commentators of Hippocrates, Galen, Celsus, and Aretaeus have exhausted themselves in vain conjectures to ascer- tain to what alteration of tissues aphthae are to be referred." And Boerhaave, Van Swieten, Stahl, Armstrong, and Under- wood applied the term to ulcers, whatever may have been their origin. Others, such as Sylvius, Mercurialis, Ettmuller, and Pinel, regarded aphthae as being vesicular pustules with a red border and a white centre.2 Billard describes his own concep- tion thus: " The projecting points are neither tubercles, as M. Gardien has said, nor pustules, as has been said by others ; but they are evidently the muciparous follicles, as their central ori- fices and unvarying form demonstrate.3 The inflammation of the follicle is sometimes arrested in the first stage, and may re- main so for a longer or shorter time without giving rise to any symptom ; but as a rule these points enlarge, and a whitish matter spreads from the central aperture over the parts around, and ulceration begins about the same time. The aphthous fol licle, once broken, consists of a superficial ulcer with a slightly tumefied, congested, and inflamed border. The whitish pulta- ceous matter which adheres to the ulcer like a scab exudes from the centre and border (of the ulcerated follicle). The scab or grayish pultaceous matter is finally washed away by the saliva which dribbles from the mouth, and the ulcer is exposed. When the aphthae are numerous they may coalesce, and the ex- uded curdy matter then forms a membrane of greater or less ex- tent and thickness."4 Bohn supplements Billard's description of Boerhaave's and Van Swieten's conceptions of this malady by saying that these great men looked upon this membran if orm development as characteristic of aphthae, but Bohn thinks they 1 The small figures refer to the bibliography at the end of the article. RUPP : APHTH.E AND DIPHTHERIA. 3 were not particularly definite.5 Billard continues: " When this curdy membrane has formed, the malady has been con- founded with thrush (mug net, Soor); but the inflamed follicles and the solution of continuity of the mucous membrane do not exist in the latter disease. Sometimes the borders of aphthous ulcers break down, and the transuding blood, becoming dry, forms brown scabs ; then these brown scab-covered little ulcers are mistaken by some observers for gangrenous eschars." With- out denying that under certain circumstances follicular ulcers might end in gangrene, Billard believed such a result rarer than Van Swieten, Rosen, Underwood, and many others had af- firmed to be the case. So far Billard. About forty years ago, and about fifteen or twenty years after Billard had clinically defined aphthae, Bamberger5 claimed that aphtha* "must be limited to that inflammation of the mouth characterized by minute circumscribed points of exudation in (not on the surface of) the mucous membrane and its mucipa- rous glands." These transuded deposits he believed to be of a fibrinous nature, and not located within the confines of the muciparous follicle only, but scattered over the subepithelial mucous membrane generally. These subepithelial fibrinous de- posits with their epithelial covering disintegrate, soften, and begin to detach themselves, first at their (the aphthae) borders, and lastly in the centre, when they are washed away by the saliva and leave a subepithelial mucosa exposed. New epi- thelium rapidly forms from the borders and quickly covers the exposed surfaces. Bamberger based his views on post-mortem investigations as well as on clinical observation. He was never able to corroborate Billard's statement that the mouth of a fol- licle could be made out at the points of exudation. The next author whom we shall quote is Bohn, and he follows Bamberger by about twenty-five years (writing in 1880), and Billard by about forty or fifty. He has written on aphthae most clearly, fully, and commendably, and he is in touch with our own times. Bohn discards the implication of the muciparous follicles altogether. In this respect Damachino ' fully agrees with him. Bohn locates the trouble or origin of the pathological process- the inflammation-under the epithelium in the superficial layer of the corium. He denies absolutely the vesicular character of this disease, and, holding too rigidly to a gross biopathological definition of ulceration, he denies its ulcerative characteristic 4 RUPP : APHTHAE AND DIPHTHERIA. too. He claims that aphthae do not develop "purulent dis- organization of tissue," and therefore cannot become ulcers. However, he does not deny that tissue disintegration and so- lution of continuity take place, very superficially of course ; and consequently, according to another definition of ulceration, Bohn's contention as to non-ulceration may be fairly rejected, al- though his definition is not done away with thereby. The late Alfred C. Post, M.D., taught us the following definition of an ulcer: " An ulcer is a superficial solution of continuity due to molecular disintegration." This is a physical rather than a biological definition, and covers the meaning of an ulcer in the result rather than the process or genesis, and in so far is inferior to a biological definition. However, I have seen typical aphthae develop into ulcers which resulted from " purulent disorganiza- tion of tissue," and Forchheimer reports that in two cases in eight "pus formers" were found. These eight cases of aphthae were carefully examined microscopically by expert microscopists or bacteriologists, and because " pus formers" were not found in the other six cases Forchheimer pronounces, without further explanation, that the find in the two cases is accidental. The entire pathological process of aphthae is a very rapid one, and very superficial too as a rule; and it will be well, therefore, to be a little guarded against a too exact biopathological definition of ulceration, at the same time not forgetting that a difference in degree is not one of kind. Bohn pointed out how much aphthous stomatitis simulated acute infectious diseases. He also drew attention to its analogy with eczema and impetigo of the skin, with which diseases he had often found it associated. The subepithelial transudation Bohn found to consist of fibrin- ous matter and young cells, and blood only when the corium had been injured ; but he failed to discover bacteria and fatty matter besides, as others had.7 Coming into our own day, we find the affection classified by Frankel as a pseudo-diphtheritic disease, the exudation being fibrinous and with an absence of normal epithelium in the plaque. The seat of the plaque being congested and inflamed, Frankel found here different kinds of micro-organisms-cocci, especially staphylococcus citreus and flavue, bacilli, yeast cells, and mycelium.8 But, to quote Ru- ault, the discovery of the specific micro-organism which gene- rates all the pathological processes which have been observed RUPP : APHTHAE AND DIPHTHERIA. 5 by the different authors who have been quoted remains a micro- biological question awaiting solution. And now, at the risk of being tedious, the foregoing outline history of aphthae may be summarized and divided into five periods. The first period comprises the long stretch of years, over two thousand, from Hippocrates to Billard, during which no definite conceptions of aphthous stomatitis were formulated and generally accepted. The second period is typified by Bil- lard's clearly cut clinical description, but explained by a purely hypothetical and erroneous patho-anatomical assumption. The third period is a transitionary one, and is marked by Bamber- ger's modification and partial correction of Billard's pathological anatomy. Bamberger does not altogether exclude the implica- tion of the follicles, but makes the subepithelial mucous surface the seat of the inflammation and localized deposits. The fourth period is characterized by still clearer clinical conceptions and more definite pathological and anatomical notions, which may be stated as follows: A general congested state of the mouth, possibly, though less frequently, also the throat, ushers in the appearance of firmly dotted points of fibrinous deposit under the epithelium. Although the corium participates in the conges- tion, the deposit takes place on, but not into, it. These deposits are usually described as varying in size from a pinhead to that of a lentil, and as having a more or less well-marked congested border. According to my own observations-which I have frequently made with the aid of an ophthalmologist's magni- fying lens and a reflecting head mirror in good daylight-these deposits are at first all of them very minute points. Very often they can be brought into view by putting the mucous mem- brane on the stretch, when otherwise they would escape detec- tion even by means of the magnifying glass and reflected light. This would seem to point to a dulness of the epithelial layer of the mucous membrane. Quite rapidly many or only some of these minute points enlarge discretely or by coalescence. In very many instances I could not observe the much-described red border-not even around the larger aphthae ; but at times it was very well marked. However, these little dots may coal- esce so as to form serpiginous streaks between the papillae of the tongue (Bohn), or oval or irregular patches. When the thin saliva is flowing over these little dots of fibrinous deposits a very illusory picture of vesicles is presented ; but if the saliva 6 RUPP : APHTHJE AND DIPHTHERIA. is wiped away, and the parts are then examined in a good light by means of a magnifying glass and a reflecting mirror, a very different picture will be seen. The entire mucous surface will be found to present a dull aspect, and these aphthae as duller deposits under the immediate surface. Examining by this means, I have never been able to detect any vesicles in the shape of aphthae. Bohn (and he quotes others who) failed to find any fluid in aphthae by pricking them. Hence we may conclude that aphthae never begin nor are at any time vesi- cular. Aphthae are frequently associated with other mouth affections, especially ulcerated stomatitis, and besides occur along with constitutional diseases and measles, scarlet fever, malaria, and diphtheria, etc., etc. In two hundred cases Bohn found this disease affecting children from 10 months to years old one hundred and forty times. Bohn's statistics also show the malady to be most frequently met with during the summer and autumn months. The fifth period is the as yet incomplete bacteriological period-our own and the future. II. Diphtheria and Aphthae.-All of us have seen cases which tallied with what Sir William Jenner teaches,0 namely : " You may often suspect that the disease is diphtheritic before the exudation occurs, and sometimes be almost certain that it is so ; just as in measles or scarlet fever you may venture on a dia- gnosis before the anatomical character-i.e., the eruption-has appeared." However, in other cases our suspicions remain such until further developments allow us to settle on a trustworthy diagnosis. Suspicions always take much for granted; and al- though it is always easy to take a diagnosis for granted, it is none the less often a judicious and safe procedure. Diphtheria isalways a mean disease to deal with, and the negative bacte- riological examination of clinically indefinite cases does not always justify us to " go slow" in our treatment. On the other hand, cases turn up presenting exudative phenomena in the mouth and throat which, whether examined hastily or carefully, may mislead us into the mistake of calling them diphtheritic. Not by any means a serious mistake. Mistakes of this kind have been made much oftener in bygone times than is done nowadays, no doubt. When aphthae and diphtheria and thrush were looked upon as identical diseases such mistakes were nec- essary and natural. And so when we are studying the statis- tics and allied matters having to do with diphtheria prior to RUPP : APHTHAE AND DIPHTHERIA. 7 Bretonneau's and Dillard's times, it will be helpful in arriving at true conclusions to bear this in mind. Bohn 10 instances the case of Stark, of Jena, translating and editing a Dutch work on diphtheria about 1784, who shows by his annotations that much of his (Stark's) knowledge of diphtheria was mixed up with a knowledge derived from his observing cases of aphthae. It has been asserted over and over again that Bretonneau marked the distinctions between diphtheria and aphthae about 1826. Al- though the statement is not without some foundation, it is not altogether correct. However this may be, evidence is not want- ing that good observers since then up to the present time have been puzzled by some of their cases, for a little while at least, before they could determine whether or not they were deal- ing with diphtheria. In 1851 Dr. John Grove read a paper on aphthae, thrush, and diphtheria, and their relations,11 before an English society. The outcome of the paper was that " in all probability muguet (Soor, thrush), aphtha, and diphtherite were associated affections depending on a common primary agent as a cause of disease." Furthermore, Grove argued, "the most curious part of this inquiry is that the more severe diph- therite, aphtha, and muguet are, the more constitutional the other symptoms become allied ; whereas in distinct diseases the reverse obtains, for the more marked and characteristic the symptoms of any specific affection are, as a rule, the more clearly defined they become in proportion to their severity." Confused conceptions of this kind were shared by others at this time, and Grove quotes Bennett to corroborate his views. But even now, though guided by better founded pathological theories and clearer clinical conceptions, observers meet with cases con- cerning which a satisfactory diagnosis in these matters cannot be immediately formed. Francotte12 reports five cases which at first he could not positively determine the nature of ; finally he pronounced them to be cases of aphthse, and not diphtheria. This was in 1880. I will briefly quote his Case 5: Boy, 21 months old. Vomiting and diarrhea preceded convulsions. A day or two after the convulsions the parents noticed some- thing wrong with his mouth. The child was seen by Francotte four or five days after the convulsions. He found grayish plaques on the gums of the lower jaw near the incisors, and on the dorsum and under surface of the tongue near its tip. The mucous membrane of the gum of the lower jaw was lightly 8 RUPP : APHTH2E AND DIPHTHERIA. ulcerated under the plaque. One week later the plaque on the tongue had become thinner and slightly scooped, that on the under surface had thickened. After three more days every sign of a plaque had disappeared. Three weeks after the child's last visit at the clinic, smooth, superficial depressions could be seen occupying the former site of the plaques, which it was supposed marked the ulcerations before mentioned. At the beginning of the trouble the child had fever, and during the course of the malady his breath -was only slightly, if at all, malodorous. Some might suspect that Francotte had not made a correct diagnosis of this case. But in this connection Sir M. Mackenzie may be quoted: " When aphthae become confluent the whitish pultaceous matter which breaks up on being touched can easily be distinguished from the homogeneous, closely ad- herent, and tough membrane of well-marked diphtheria; but there are some cases which bear a middle ground and are very difficult to differentiate." 13 When aphthae become confluent a late stage, though not the last in their process, has been reached. Moreover, confluent aphthae are not seen very often. Barthez and Rilliet,14 who claimed never to have seen this form, stated that those who had claimed that that form had been seen really saw diphtheria or a complication of diphtheria and stomatitis membranacea. These writers, excellent as such, were too posi- tive, even in their day, in making diagnoses from observations made by others than themselves. Every eventuality does not turn up (or is not noticed) in the experience of those honoring themselves with the most ample experience. Forchheimer 16 makes the statement-whether based on his own or the expe- rience of others he does not state-that sometimes the whole mouth becomes covered with an aphthous exudation and looks the picture of diphtheritic inflammation. Bohn, whose obser- vations have been numerous, saw only a few such cases. I have seen only one such case, but this was associated with tonsillitis and rheumatism, and, having been seen from the start, it would not have been easy to have mistaken it for diphtheria. The mouth affection was first, then the tonsillitis, and last the sub- acute rheumatism. But had this case been seen during the tonsillar stage of its progress it might have been taken for diph- theria. Different writers hit upon different stages of these diseases in their descriptions of them as they occur individ- ually-from the point of view of differential diagnosis-and RUPP : APHTHA AND DIPHTHERIA. 9 as they occur associated. This may be due a good deal to the run of their experience and to other causes into which it is not necessary to inquire here. And so Jacobi, writing in 1880, though his description of aphthae disappoints one because it is dominated by the antiquated nomenclature and pathology ori- ginated by Billard, presents the subject of the "side-by-side" occurrence of aphthae and diphtheria, and in a light different from that in which they have been viewed heretofore. Jacobi says: " Stomatitis follicularis can hardly fail to be recognized by the gray discoloration of the superficial ulcerations. Such patches are very numerous in the fauces, and on the lips, on cheeks, and never on the gums except in ulcerative stomatitis which is not follicular. They are accompanied, too, by vesi- cles, containing more or less serum, which have not yet rup- tured. It must be remembered, however, that the mucous membrane, when deprived of its superficial covering, is liable to become infected, like every other wound. I have seen cases in which stomatitis and diphtheria existed side by side, the lat- ter having invaded the exposed surfaces resulting from the former." It will have been noticed that Jacobi's description is somewhat unique. His description does not tally with her- petic stomatitis, and we may be sure it is not thrush of which he is speaking. I have never seen the state of. affairs whereof he speaks. Furthermore, all so-called ulcers of aphthous sto- matitis do not become diphtheritic. My experience rather sub- stantiates Forchheimer's remark: "It is barely possible for the ulcers of this disease to become infected with other processes, but it is fortunately of rare occurrence." 17 Aphthae affecting the fauces and tonsils seem to be more vulnerable than those found on the tongue, cheeks, and lips, and perhaps here, when conditions are favorable-i.e., when diphtheria is about-the chances of infection are greatest. In a case of mine, reported below, diphtheria existed in the nose, on the tonsils, and on the soft palate, and yet the denuded or ulcerated aphthae on the tongue, lips, cheeks, and floor of the mouth pursued their wonted course, undisturbed by the propinquitous diphtheritic processes. This case was under observation from October 24th to November 12th, 1893, when the child was declared conval- escent. The parents of this child are splendidly developed p.eople of Irish descent. The child-a boy-is 22 months old and is still nursed at his mother's breast. The little fellow 10 RUPP : AI'HTH.E AND DIPHTHERIA. is quite small for his age, is rickety but not bowlegged, and anemic. The rickets is probably due to bad feeding and in- sufficient out-door airing. On several occasions before, he had convulsions when teething, but at no time had the convul- sions been so severe as at the present time. From 4 up to 9 p.m. (October 24th) he had six convulsive seizures. When first seen he was just recovering from the sixth, was somewhat cyanotic, and the muscles of the face and extremities twitched irregularly. There was no heavy breathing, but the child, though drowsy, could readily be brought to; then he would doze off again. The pupils were dilated, but reacted to light, and there was no pupillary inequality. Rude breathing was found all over the chest, and here and there a large r&le- nothing specific. The abdomen was swollen and hard. The pulse was rapid, but not otherwise abnormal. Examination of the throat negative by poor lamplight. The child suffered from constipation. The day before (October 23d) he had been allowed to have a good time with several raw apples, bananas, and pastry. Temperature in the axilla 103.5° F. The child having had convulsions before, the people had administered on this occasion mustard baths, enemata, castor oil by the mouth, and a mixture which w'as kept ready in the house for emergen- cies-" to prevent convulsions," the mother said. However, nothing had been done properly for the child's relief. Besides other specific directions and corrections, a mustard poultice was ordered to be applied along the spine, and two grains each of antipyrin and bromide of soda every two hours internally, but not if the child slept. I had hardly left the house when the child had a seventh convulsive seizure. October 25th I was requested not to call, because it -was sup- posed the child was doing well enough not to need a physician. October 26th I was asked to call on the child again, because he had fever, and patches in his mouth. The axillary temperature was F. Aphthae were found on the tongue, along the edges especially toward the tip, on the dorsum and under sur- face too, on the inner surface of the lower lip, fauces, and ton- sils-the tonsils swollen. The child swallowed without apparent pain. Ordered a borax and glycerin wash for the mouth, and two drops of tinctura ferri chloridi in water every hour. October 27th I found child playing on the floor with his father; the whitish aphthous patches in great part gone, and where so, RUPP : APHTII.E AND DIPHTHERIA. 11 superficial ulcers or denudations rapidly healing ; the little patches on the tonsils and pharynx dirty-looking, and, when wiped away with moist absorbent cotton, superficial bleeding surfaces are left. There is much dribbling from the mouth, a slightly tainted odor to the breath. There is a slight watery mucous discharge from the nose. There is no cough, no cramp symptoms. Child slept well through the night. October 28th (fifth day of illness): Child did not sleep well last night. Glands at the angles of the jaws swollen-at the left side much more so than on right side. Dribbling at mouth less than yesterday. Slightly feverish. Tonsils covered by a dirty- whitish patch, and arching up behind the palate on the left side. These patches could be wiped away only partially, and where this was done a raw, bleeding surface was brought to view. The discharge from the nose is thicker from the left than from the right nostril. After syringing about an ounce and a half of bo- rated water through the right nasal passage, a large, clotted, dirty- white mass of muco-fibrinous matter and muco-pus came away, in quantity enough to fill a teaspoon. This was followed by blood- tinged mucus. Injecting the water through the left nostril caused only purulent mucus to come away from the right side of the nose. The child was very much relieved by the nose- cleaning. The nose was ordered to be syringed every two hours, the iron tincture to be given every half-hour, and the child to be fed on soups, broths, and scraped beef. October 29th: Discharge from the nose continues muco- purulent, the discharge from left nostril thicker than that from right. The glandular swelling at the angle of the jaw on the left side perceptibly increased. The tonsillar patches thicker and of a yellowish-green tint, but they have not spread; did not attempt to wipe them away. Syringing of the mouth and pharynx, as well as of the nose, continued. October 30th (seventh day of illness): Child slept well last night, and wants to play around. Patches on tonsils have be- come smaller, but have spread forward on to the soft palate and anterior faucial pillars-more especially so on the left side. Carl Seiler's solution now used instead of borated solution. Discharge from the nose less puriforin and less in quantity. October 31st: Child coughs as though it were whooping cough -had whooping cough four months ago; coughs up a tenacious, puriforin mucus. Child is not hoarse, breathes easily, has a 12 RUPP : APHTHAE AND DIPHTHERIA. moderate bronchitis. A laryngoscopical examination is impos- sible. The same treatment is continued. November 1st: Child feels well, but coughs much and with a whoop. Coughs and whoops when he gets excited. Irregular small patches on the tonsils and faucial pillars. Glandular swell- ing at angles of the jaw almost gone. November 2d (tenth day of disease) : Diphtheritic patches on the right side of the fauces all gone, and almost so on the left side. Nasal syringing kept up into the nose and mouth, but at longer intervals. Child during last two nights was awakened only once to clean the nose and throat; on previous nights he had been syringed into the nose and mouth every three hours. Mucus from the nose now almost white, and thick. The cough and whoop are less, and there is no hoarseness. November 6th : Child coughs much, but there is very little bronchitis. He is not hoarse. No discharge from the nose. Syringing the nose now brings away only clear mucus. On the centre of the left tonsil a small, membranous patch persists, but is removed by a solation of papoid, a bleeding surface re- maining. The child has a good appetite, is constipated, and coughs up a yellowish-green mucus which probably comes from the pharynx, larynx, and trachea. November 10th : The child is doing well in all respects. December 31st: The child has had no paretic symptoms. A number of interesting speculations might be based on the case just narrated, but, having already drawn liberally on your kind, indulgent attention, I will close this paper by directing your attention to two or three points relating to the two subjects that have been discussed, and which the case just narrated illus- trates. In the first place, the origin of the case was ordinary enough. A rickety, over-indulged child is seized with convul- sions. After the bowels had been cleared and the child had slept, the next day finds it well enough not to need the physi- cian, in the family's estimation. Then the diagnosis of aph- thous stomatitis is made ; and had the description which the majority of the text books give been relied on entirely, no doubt grievous effects might have resulted from a too optimistic diagnosis. The two diseases probably began their work at about the same time, but the more active and benign malady masked the early stages of the grave disease. The swelling at the angles of the jaw aroused suspicion in connection with the running 13 RUPP : APHTH2E and diphtheria. from the nose, more so than did the swollen condition of the tonsils. Barthez and Rilliet18 had observed that aphthae may occur on the tonsils, but rarely. Ashby 19 also notes the occur- rence of aphthae and tonsillitis, temperature reaching 103° F. I would here recall the case of aphthae, tonsillitis, rheumatism, mentioned awhile ago. And, finally, the aphthae on the lips, tongue, and floor of the mouth healed undisturbed by the near- by diphtheritic processes. 1 might also state that the diagnosis of diphtheria in this case was confirmed by the bacteriological department of the Board of Health. It has not been an object of this paper to consider bacteriological differences. 406 West 34th street. BIBLIOGRAPHY. 1. Billard, C. M. : A Treatise on Diseases of Infants. Translated by James Stewart, M.D. New York and London, 1840. 2. Billard : Op. cit., p. 171. 3. Billard : Op. cit., p. 172. 4. Billard: Op. cit., p. 173. 5. Virchow's Handbuch d. spec. Pathologic und Therapie, Band vi., 1. Abtheilung, p. 55. F. Enke, Erlangen, 1855. 6. Traite de Medecine, tome iii., p. 23, quoted by A. Ruault. 7. Bohn in Gerhardt's Handbuch der Kinderheilkunde, Band vi., 2. Abthei- lung, pp. 5, 9, 33. 8. Baginski, A. : Lehrbuch der Kinderheilkunde, Berlin, 1892, p. 651. 9. On Fevers and Diphtheria, etc., p. 529. Macmillan, 1893. 10. Bohn : Loc. cit.,p. 6. 11. London Medical Times, vol. xxiv., 1851, p. 91. 12. Francotte : Die Diphtheric, pp. 207 and 208. Spingler's edition, Veit & Co., Leipzig, 1880. 13. Mackenzie, Sir M.: A Manual of Diseases of the Throat and Nose, p. 118. London, 1880. 14. Barthez and Rilliet : Handbuch der Kinderk., E. R. Hagens, Ed., p. 232. Leipzig, 1855. 15. Forchheimer : Diseases of the Mouth, p. 41. 16. Jacobi, A. : Treatise on Diphtheria, p. 134. Wm. Wood & Co., New York, 1880. 17. Forchheimer: Diseases of the Mouth, p. 41. 18. Barthez and Rilliet : Edition cited, i., p. 231. 19. Ashby and Wright : Diseases of Children, Northrup's edition, 1893, p. 53. MEDICAL JOURNALS PUBLISHED BY WILLIAM WOOD & COMPANY. MEDICAL RECORD. A WEEKLY JOURNAL OF MEDICINE AND SURGERY. 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