HX64 148840 RC1 38 .P22 Diphtheria and allie RECAP PABKER DIPHTHERIA 9vU3£l E£^ Columbia 29nit)er^ftp College of 3^iiv&itim& anb ^urgeong Digitized by tine Internet Arciiive in 2010 witii funding from Open Knowledge Commons http://www.archive.org/details/diphtheriaalliedOOpark '•viombia Univere DIPHTHERIA AND •Allied Pseudo-Membranous Inflammations A CLINICAL AND BACTERIOLOG- LCAL STUDY WILLIAM HALLOCK PARK, M.D. NEW YORK Repritiied f7-07n the Medical Record, July 30 and August 6, 1892 NEW YORK TROW DIRECTORY, PRINTIirG AND BOOKBINDING CO. 201-213 East Tw clfth Street 1 892 Diphtheria and Allied Pseudo-Mem- branous Inflammations. A CLINICAL AND BACTERIOLOGICAL STUDY* The diagnosis of diphtheria has always been a subject of extreme' importance in medicine. Are all cases of diffuse pseudo membranous inflamma- tion of the upper air-passages, and all cases of membra- nous laryngitis, rhinitis, and tonsillitis the local manifesta- tion of one disease — diphtheria ? Are all these cases equally contagious and equally dangerous? These are questions which occur daily to the minds of practi- tioners. The marked differences noticed in different cases have always forced on physicians the possibility that, under the term diphtheria, we may include more than one disease. When it was discovered that two different conditions ex- isted in pseudo- membranous inflammations it was hoped that here we had a reliable diagnostic sign. One is a gangrenous inflammation, in which there is superficial ne- crosis, leaving on the removal of the adherent pseudo - membrane a bleeding surface ; the other is an exudative inflammation, leaving on the removal of the loosely at- tached deposit an intact surface. The first was sup- posed to occur in true diphtheria, the second as a result of some local irritant, either chemical or bacteriological. Experience proved this test, like so many others, unreli- able, and most clinical observers still thought it wisest to consider all pseudo membranous inflammations as if they were the local expression of the acute infectious disease which we call diphtheria. Since the discovery of the existence of bacteria, and of their relation to disease, a new hope has arisen that by the bacteriological examination of these pseudo-mem- branes we might get a truer knowledge of the disease * Alumni Association College of Physicians and Surgeons Prize Es- say, with additional cases. 4 DIPHTHERIA AND ALLIED called diphtheria, and settle the question, whether or no, under this name we should include more than one dis- ease. At the outset the difficulties were very great, owing to the multitude of bacterial forms present in the mouth. However, persistent investigation, aided by the improved methods of bacteriological study, has overcome all these obstacles. Although recent reviews by Loeffler,' Welch, ^ and others makes it almost unnecessary, it is thought best, in order to have the whole subject fresh in mind, to give as briefly as possible the reasons which have led to the ac- ceptance of the Klebs-Loeffler bacillus as the cause of true diphtheria, this sketch to be followed by a summary of the chief characteristics of the bacillus, and the more important lesions produced by it. Finally, to present the evidence that a streptococcus is the most frequent agent of infection in cases of pseudo-membranous inflammation in which the Klebs-Loeffler bacillus is absent. True Diphtheria. — In the year 1883, Klebs ^ demon- strated, morphologically, the constant occurrence of a bacillus in the pseudo membranes of those subject to epi- demic diphtheria. Loeffler,* in 1884, published the re- sults of a very thorough and extensive series of investiga- tions. He found the bacillus described by Klebs in the pseudo-membranes in nearly all cases examined. He proved by inoculating that this bacillus was pathogenic in certain animals. When inoculated on the injured mu- cous membrane it produced a pseudo-membrane some- what like that present in human diphtheria. He failed to find the Klebs bacillus either in the blood or organs of fatal cases of human diphtheria, or in the same re- gions of animals dying after inoculation. He came to the conclusion that the Klebs bacillus was the probable cause of true diphtheria. He considered, however, that further investigations were necessary to prove his conclu- sion. Since then the whole subject has been examined with great care, not only by Loefiler himself, but also, inde- pendently, by a large number of investigators, both in Europe and America. The work of Roux and Yersin,^ in Paris; Loeffler, in Berlin ; Kolisko and Paltauf," in Vi- enna; Ortmann,' in Konigsberg; Zarniko,^ in Kiel; Es- cherich," in Munich; Beck,'" Brieger," and Fraenkel,'^in Berlin ; Tangl,'' in Tubingen; Babes,'' in Bucharest; d'Es- pine," in Geneva; Klein, '" in London ; Welch and Ab- bott,''^ in Baltimore ; Prudden,'' in New York, and many others, has established that in all cases of typical infec tious diphtheria the Klebs-Loeffler bacilli are present in large numbers in the pseudo -membranes, either alone or associated with other bacteria, and that the Klebs-Loef- PSEUDO-MEMBRANOUS INFLAMMATIONS. 5 fler bacilli in all other inflammations of the throat and in healthy throats are very rarely found„ Pseudo-membranes, paralysis, and organic lesions can be produced in inoculated animals, similar to those found in human diphtheria. A toxine is produced by the bacilli which, when isolated and inoculated, produces the same results, with the exception of the pseudo-membrane, as the pure cultures. All the conditions have now been fulfilled which are necessary to the proof of the dependence of true diphthe- ria upon the bacilli described by Klebs and Loe filer. The Klebs-Loefiler Bacilli. — They are moderate-sized rods, usually slightly bent, averaging nearly as long as the tubercle bacilli, but twice as broad and usually with rounded ends. According to the rapidity of growth, the soil, and other conditions, the form and size of the micro- organisms varies, and the differences are striking in ap- pearance. The bacteria are sometimes enveloped in a more or less capacious membrane ; sometimes the con- tents divide into a number of pieces, separated by trans- verse divisions ; one end of the rods is frequently thick- ened like a club, or both ends may be clubbed, or one or both pointed. The bacilli are immobile and have no spores. The best staining agent is Loeffler's alkaline methyl blue. Some forms stain uniformly, others in vari- ous irregular ways, the most common being the appear- ance of deeply stained granules in a slightly stained bacil- lus, or of darkly stained ends with a paler centre. The bacilli are very often in pairs, never in chains ; they are semi-anaerobic, and thrive only at a somewhat high tem- perature, 20° to 42° C. The Loeffler bacilli can be cultivated upon all the ordinary culture-media, but grow most vigorously on a Surface Colony of Klebs- Loeffler Ba- Klebs-Loeffler Bacilli, highly cilli, on Agar Plate, slightly magni- magnified, fied ; twenty hours' growth. mixture of blood serum and nutrient bouillon, as given by Loeffler. On this, solidified, the bacilli grow as large, round, elevated, grayish-white colonies, with the centre more opaque than the somewhat irregular per- iphery. 6 DIPHTHERIA AND ALLIED Th.e Sections of Diphtheritic Membrane show on the surface and in the most superficial portions of the pseudo- membrane Loeftier bacilh mixed with more or less nu- merous other micro-organisms. In the middle and deep- er portions the Loeffler bacilli, alone or associated with streptococci, are usually the only organisms present. In the deepest layer there are very few bacilli and in the mucous membrane, as a rule, none. Extremely rarely they are found in the blood and viscera. Some of those bacteria which are associated with the Klebs-Loeffler ba- cilli in diphtheria, especially the streptococci, may be found in the mucous membrane, lymphatic glands, and internal organs. Toxic Albumins. — The toxic albumins produced by the diphtheria bacilli have been especially investigated by Roux and Yersin,-^ and Fraenkel and Brieger."" This toxic substance is of a proteid nature, precipitated by alcohol, soluble in water. Nearly pure, it is a white, amorphous mass of light specific gravity, and keeps its properties for a long time unchanged. Its extraordinary poisonous nature is shown by Roux and Yersin, in that four tenths of a milligramme of the substance, when in- oculated, was sufficient to kill eight guinea-pigs. If this poison be inoculated into a guinea-pig, it produces all the changes, except the pseudo-membrane, that the pure culture of the bacilli does. The long continuance of the toxic power of the poison in the body and its slow absorption from the locally infected tissues ac- count for the deaths which occur some time after the entire disappearance of the bacilli from the infected throats. The toxalbumin of diphtheria is very little, if at all, absorbed by intact mucous membranes, and can be swal- lowed by susceptible animals in large amounts, without danger. Lesions. — In animals inoculated with the bacilli or these toxalbumins we find at the seat of inoculation a grayish focus surrounded by an area of congestion. The subcutaneous tissues for an extensive area around are congested and more or less oedematous. The adjacent lymph-glands are swollen and the serous cavities usually contain an excess of clear or turbid fluid. The micro- scopical changes in the internal organs of animals dying of experimental diphtheria have been studied by Babes," Welch"^ and Flexnor, and others. In the liver there are found numerous smaller and larger masses of necrotic cells. These areas are perme- ated by leucocytes. Congestion with hemorrhages into the capsule and tissue are present. In the kidneys fatty changes occur in the epithelium of the tubes and glome- PSEUDO-MEMBRANOUS INFLAMMATIONS. / ruli and a hyaline alteration of the glomerular capillaries and of the smaller arteries. In the spleen and lymph- glands the necrosis of cells is also present. Both the cell-bodies and nuclei of living cells are altered. The lungs show areas of intense congestion with hemorrhages into their tissue. The heart is nearly always the seat of fatty degeneration. The fibres of the voluntary muscles show degenerative changes. The number of leucocytes is greatly increased in the blood. Experimental Immunity. — The exceedingly interest- ing results obtained by Fraenkel, Behring,^' Brieger,^* and others '^ in producing immunity in animals, gives the hope at least of practical results in the future. They found that the blood or serum of animals rendered immune against diphtheria had the power of rendering other ani- mals, when injected into their bodies, also immune. In animals already infected the injections had the power of destroying or neutralizing the poison secreted by the ba- cilli. It was also found that the offspring of immune animals possessed a considerable degree of immunity. Their success in treating animals has been so great that the endeavor to cure human diphtheria is soon to be made. , Duration of Life in the Kiebs-Loeffler Bacilli. — The life of the bacillus varies greatly according to the condi- tions under which it is placed. An agar tube-culture in the laboratory is still alive after seven months' growth, and a bit of membrane no larger than a pin's head still gives cultures of both the bacilli and the streptococci four months after its removal from the throat. Some have found bits of membrane kept in cloth to be still alive after six months. Probably in dark, damp, dirty places life remains even longer, while, on the other hand, under unfavorable conditions the bacilli may live only a few days. The Conditions Necessary for the Infection of Man with the contagium of diphtheria are of great practical im- portance. Whether this can be implanted on the normal mucous membrane in man is still a question. Undoubt- edly a lesion favors it. When the Klebs-Loeffler bacilli are implanted on the normal mucous membranes of sus- ceptible animals they do not grow. The researches of Barbier "° throw interesting light on this subject He found that a streptococcus which was associated with the Loef- fier bacillus in all cases where marked redness and swell- ing were present, when implanted on the normal mucous membrane of the vagina in guinea-pigs, produced an acute purulent discharge, with redness and swelling. If with these cocci, or even four weeks later, the Loeffler bacilli were brought into contact with the mucous mem- 8 DIPHTHERIA AND ALLIED brane, a severe diphtheritic irflammation was started which often caused death. If these results can be ap- pHed to man, they add a new importance to the discov- ery that streptococci are frequently present in slightly in- flamed throats, and to their frequent association in the pseudo-membranes with the Loeffler bacilli. Psendo- Diphtheria Bacillus. — The relation of this ba- cillus to that of true diphtheria is of much practical im- portance. Abbott " has recently given such an exhaustive review of this subject that it will only be necessaiy here to give a brief summary. The term is now used to de- fine a group of bacilli which closely resemble the Loef- fier, but which are without pathogenic properties in guinea- pigs. By some writers the term is used to cover varieties that show quite marked cultural and morphological dif- ferences. It has been established that bacilli with all the charac- teristics of the Klebs-Loeffler, except their virulence, are to be found exceptionally where pseudo-membranes are absent. These are never numerous, only a few scattered colonies being found on plates or tubes. In some locali- ties they are found rather frequently, in others rarely, or- not at all. Roux and Yersin ^^ found also that among those obtained from cases of diphtheria there were gra- dations in virulence from those whose inoculation caused death in guinea pigs in twenty-four hours to those which produced only local changes. They found that those taken from mild cases are, as a rule, the least virulent. Beck found in some cases of true diphtheria both viru- lent and non-virulent bacilli. As the result of a large number of experiments, Roux and Yersin hold that the morphological and cultural dif- ferences between the diphtheria and the pseudo-diph- theria bacilli are inconstant, and, when present, are in- sufificient to establish that they belong to different species. In this country the pseudo-diphtheria bacilli have been infrequently found. Prudden, in a large number of cases in New York, did not find them once. Koplik has found them a few times, and Abbott in fifty-three cases in four. In these studies the pseudo-diphtheria bacilli were met with only once, as proved by animal experiments. This whole subject needs further study. For bedside diagnosis all cases which give typical colo- nies of bacilli resemWing the Klebs Loeffler should be regarded as true diphtheria ; both because of the length of time consumed in animal experiments and of the im- possibility of being sure that because the colony from which the inoculating culture was made was not virulent all the colonies were the same. This merely compels a few doubtful cases of diphtheria to be still considered as such. PSEUDO-MEMBRANOUS INFLAMMATIONS. 9 Pseudo-membranous Inflammations in which the Klebs- Loeffler Bacillus is Absent. — The presence of strepto- cocci in the pseudo membranes and in the blood of fatal cases of diphtheria has been known for many years. Loeffler,^' in 1884, described a class of cases where loss of substance with a gray yellow or necrotic base was a characteristic feature in which the Klebs-Loeffler bacil- lus was absent, but a streptococcus very abundant. He concluded that in these cases the frequency of the pres- ence of the streptococci either means that the poison of diphtheria has been at first present, and thus prepared the way for the streptococci, and then vanished before examination, or that the streptococci are the cause of this peciiliar form of pseudo-membranous inflammation. He came to the conclusion that the first supposition was the true one, that the streptococci were secondary to the Klebs-Loeffler bacilli. ■■^'^irf*H. h^^i^ Streptococcus Colony, slightly magnified ; Streptococci, highly mag- twenty hours' growth. nified. This streptococcus he isolated in three cases from the tonsils and in two cases from the internal organs. Both the biological characters and the general effects upon inoculated animals seemed to indicate a close relation- ship with the streptococcus pyogenes and erysipelatus. The changes produced upon the mucous membrane by its inoculation did not resemble closely the cnaracteristic local lesions of diphtheria. From that time until the present year it seemed to be the aim in Europe, espe- cially in Germany, to seek out for examination only typ- ical cases of epidemic infectious diphtheria. In these cases the Klebs Loefifler bacilli were constantly found, and they came to be looked upon more and more as the only etiological cause of all extensive pseudo-membra- nous inflammations, at least when they were not compli- cations of infectious diseases. In 1889, Prudden ^° published the results of a very careful bacteriological investigation of twenty-four cases of fatal pseudo membranous inflammation of the tonsils, pharynx, and larynx, which were all considered clinically lO DIPHTHERIA AND ALLIED to be diphtheria. These cases were mostly young chil- dren in two asylums where they had been exposed to scarlet fever and measles, and in some of whom these diseases had existed as a complication. In not one of these were the Klebs-Loeffler bacilli found, but in all but two streptococci. These were present in most of the cases in enormous numbers, as shown by the cultures. In three cases in which the viscera were examined they were found to contain a moderate number of strepto- cocci. In the ducts of the mucous glands and in the lymph-spaces of the submucosa, the streptococci were found in greater or smaller numbers, also rarely in the tracheal and bronchial glands. The staphylococcus py- ogenes aureus and albus were present in varying num- bers, but hardly more frequently than in many apparently normal throats. In sixteen of the twenty four cases, broncho-pneu- monia ^' was present, and cultures made from the fresh broncho-pneumonic areas in fifteen of these gave large numbers of streptococci. The streptococci obtained from all these cases presented the same morphological and biological characters. They appeared to be identi- cal with the streptococcus pyogenes. From his investigations Prudden concluded that in a certain class of cases pseudo-membranes were caused by streptococci. Kolisko and Paltauf, Wurz and Bourges,^" Sevestre,^^ Tangl,^* Baginsky,^^ and others have found streptococci but no Loeffler bacilli in the pseudo-mem- branous inflammations occurring early in scarlet fever. Baginsky,^^ in his recent studies, found that in one hun- dred and fifty-four cases clmicaily diagnosed as diph- theria, there were thirty- four in the pseudo-membranes of which no Loeffler bacilli were present. In two cases of membranous rhinitis he found the bacilli present. These ran the usual mild course. Martin,^'^ in Paris, has just pubUshed a clinical and bacteriological study of the croupous deposits of two hundred children suspected of diphtheria. He found in seventy-two no Klebs Loeffler bacilli; of these, twenty- nine were croup cases. The mortality of these was far less than in those having true diphtheria. Some of the children had been exposed to scarlet fever and measles. He is of the opinion that the certain clinical diagnosis of these cases is impossible. A few examples of infection with diphtheria in the wards are given. He regards the association of different bacteria with the Loeffler bacilli as greatly modifying the course of the disease. As he used only blood-serum tubes, he probably has often overlooked the almost invisible colonies of the strep- tococci. He also believes that from the form of the PSEUDO-MEMBRANOUS INFLAMMATIONS. II Klebs-Loefifler bacilli one can judge somewhat of their virulence. Aim and Scope of these Investigations. — The object of these studies has been to determine by the bacterio logical examination of a large number of cases whether, in fact, pseudo membranous inflammations can be divided into two distinct classes, and, if so, in what proportion of the cases the Klebs-Loeffler bacilH are present ; also to go further and see if, by combining in all cases a very careful clinical examination with a bacteriological one, it would not be possible to iind some constant differences between the local appearances and general symptoms of true diphtheria and those pertaining to other croupous inflammations. The cases recorded in the following pages include all those having pseudo-membranous inflammations admitted to the wards of the Willard Parker Hospital during four consecutive months ; also a number sent to me by sev- eral physicians, and six cases of membranous rhinitis from the throat classes of the Vanderbilt Clinic and the Roosevelt Hospital. In all, one hundred and fifty-nine were examined ; these will be studied in the following classes : True diphtheria, those in which the Klebs-Loeffler bacilli are present alone or with other bacteria ; pseudo-diphtheria, those in which the Klebs-Loeffler bacilli were never pres- ent, but some form of cocci, usually streptococci. For comparison, the following were also examined bacteriologically : FoUicular tonsillitis, lo ; peritonsillar abscess, 5 ; acute pharyngitis, 5 ; chronic pharyngitis, 5 ; hyper aemic throats m scarlet fever, 10. Technical Observations. — To obtain the material for examination two methods were employed. Where a piece of membrane could be removed without injuring the throat, this was done by means of along, slender pair of forceps, carefully sterilized. For the cases in which this was impossible, a number of cotton plugs * had been prepared by wrapping small portions of absorbent cotton around the ends of slender sticks, one inch in length, which were then placed in a tube and sterilized by dry heat. Taking one of these in the forceps, it was rubbed gently, but rather firmly, against any visible pseudo-mem- * In a number of trials, in which, from the same cases, plates were made both from bits of membrane and from the swabs, the latter proved as trustworthy as the former. For the use of physicians, who supplied me with cases from outside the hospital, I kept a number of strong glass tubes, two and one-half inches in length by one-half inch in thickness. Each tube contained an absorbent cotton swab, and was plugged with cotton. The tubes and their contents were then placed in the hot-air sterilizer. These could be carried in the pocket. After use at the bedside they were returned to the laboratory, where the plates and tubes were made. 12 DIPHTHERIA AND ALLIED brane ; when none was present, the cotton was rubbed against the tonsils and pharynx. The bit of membrane or cotton plug was then gently drawn three or four times across the surface of a six per cent, glycerine-agar Petri plate, making equally distant lines of inoculation. Taken to the laboratory, here the bit of membrane or swab was drawn across a blood-serum tube and then rubbed in a few drops of sterilized water. With a sterilized platinum loop a drop of this turbid fluid was taken up and drawn across t^o or more solidified Loeffler's blood-serum tubes, and a second drop across a second agar plate. The tubes and plates were placed in the thermostat and kept at 37° C. for twenty -four hours. From the membrane, or swab, two cover-glass smears were prepared, stained with Loeffler's methyl blue solution, studied under the micro- scope, and the forms of bacteria seen recorded. On the following day the colonies of the Loeffler bacilli, when present, in every case had reached a size sufhcient to be distinctly seen on both the blood-serum tubes and agar plates, and, under the microscope, showed their extremely characteristic appearance on the latter. It is necessary to be extremely careful to have the glycerine agar famtly alkaline, to have proper peptone, and to use only fresh, moist plates, otherwise there may result an entire failure to get any growth of the Loeffler bacilli. In these investigations the special object in view was to discover in the cultures the presence, or absence, as well as the relative abundance of the Klebs-Loeffler ba- cilli, the streptococci, and the staphylococci. Any other forms of bacteria that appeared frequently or in large numbers were also investigated. The Comparative Value as Culture-media of Blood-se- rum and Six-per-cent. Glycerine-Agar.— On the solidified blood-serum mixture suggested by Loeffler the Klebs- Loeffler bacilli grow more rapidly and surely than on any other of the usual solid media. The growth of the colo- nies, though fairly uniform, is not sufficiently characteristic to certainly identify them, for certain frequently present cocci grow with almost the same rapidity and appearance. The usefulness of the serum is limited to tubes, from its slight cloudiness and the great difficulty of making plates. On glycerine-agar the growth of the bacilli is less rapid, but still vigorous when made from fresh bits of mem- brane or swabs. The gross appearance of the colonies is here also very similar to those of several forms of cocci. The appearance of the colonies under the micio- scope is, on the other hand, extremely characteristic and entirely different from those of any other bacteria occur- ring in the throat, with the possible exception of the pseudo-diphtheria bacilli. Glycerine-agar in tubes is MEDICAL RECORD. July 5oth, 1802. PHOTOGRAPHS OF PLATE CULTURES FROM DIPHTHERIA AND SCARLATINA- Park PSEUDO-MEMBRANOUS INFLAMMATIONS. I 3 much less useful than the serum, but in plates it has many great advantages, and if it were not that under certain con- ditions, when still capable of growing on the blood serum, the Loeffler bacilli are unable to grow on the agar, the agar plates could entirely replace the serum tubes. This ab- sence of growth on agar has occurred in two cases where frequent irrigation with i to 4., 000 bichloride of mercury had been employed, also from two long-dried swabs. In disinfection work, cultures would be obtained on blood serum when they no longer appeared on the agar. With these exceptions the plates always contained colonies of the Loeffler bacilli whenever the tubes contained them. Throat cultures show the most characteristic growth under the microscope when the plates are examined after remaining from sixteen to twenty-four hours in the ther- mostat. The colonies of the different bacteria common to the throat have then attained a characteristic growth and are still for the most part distinctly separate. At this time, after some familiarity with the work, you can rapidly run over the plates, placed under the microscope, with a low power lens, and acquire a knowledge not only of how many varieties of organisms are present but also the relative proportion. The colonies can then be further studied by a higher power lens and under the microscope accurately fished. For the photographs of six of the plate cultures, shown in the accompanying Plate, I have to thank my friend Dr. Edward Learning. These give the usual appearance of the plates made from fresh membranes or swabs. At times the colonies are much closer together, at other times less so than in these. They show at a glance the actual and relative size of the colonies, and to some extent their appearance after twenty to thirty hours' growth at 37° C. It can be readily seen how thor- oughly the isolated colonies can be investigated when the uncovered plate is put on the microscope- stand and each colony individually studied with any power lens desired. Explanation of Plate. Figs. I and 2 show cultures from same diphtheritic membrane — i, with numerous ; 2, with fewer colonies. The more numerous colonies are composed of diphtheria bacilli; the larger whiter ones of non- pathogenic bacilli. Fig. 3, pure culture of diphtheria bacilli from tissue of inoculated guinea-pig. Fig. 4, culture obtained by pressing a portion of a soiled sheet, re- moved from a diphtheria patient, against the media surface. Many- varieties of bacteria grew. The smaller colonies are diphtheria ba- cilli and streptococci. Fig. 5, a pure culture of streptococci from scarlatinal membrane. Fig. 6, culture from croupous tonsillitis. The exceedingly small colonies are streptococci. Some of moderate size, staphylococci. No diphtheria. In both 5 and 6 the condensation water has swept the bacteria over the plate surface, making a diffuse growth of colonies. 14 DIPHTHERIA AND ALLIED Glycerine-agar plates in which the media has been tested are sufficient when the cultures are to be made immediately from throats in which frequent antiseptic irrigation has not been used. Whenever the bacilli may have been injured from antiseptics, drying, or any other cause, the blood-serum tubes should also be used to in- sure the growth of the Loeffler bacilli. For the simple determination of the presence or ab- sence of the Loeffler bacilli the blood-serum suffices. I believe that the failure to fully recognize that there are many extensive pseudo-membranes, neither due to the Loeffler bacillus nor occurring after scarlatina, is owing to the almost exclusive use of blood serum tubes, since in tubes it is impossible to satisfactorily use the microscope to identify the smaller colonies, and before they become visible to the eye they are often overgrown by the more rapidly growing bacteria. When the colonies of the bacteria sought for were plainly isolated, tube cultures were immediately made from a characteristic colony ; when not, a sowing was made on a fresh plate and isolated colonies obtained. Animal Inoculations. — From the first or second genera- tion of the Klebs Loeffler bacilli, tubes of faintly alka- line nutrient bouillon were inoculated. The tubes were removed from the thermostat on the fourth day. Two- thirds of the clear bouillon was poured off and the re- mainder well shaken. One-third cubic centimetre of this fluid, turbid with the bacilli, was inoculated into the sub- cutaneous tissue of the side of the abdomen of a guinea- pig. Guinea-pigs were inoculated from cultures of twenty- two of the cases in which the Klebs-Loeffler bacilli were present. In nineteen death followed with typical pathological changes. In no case were the bacilli, or any other bacteria, obtained in the cultures made from the heart's blood, the liver, or spleen. In no case were any other pathogenic bacteria than the Kleb5-Loeffler bacilli obtained from the cultures made from the cedematous fluid and congested tissue in the immediate neighborhood of the point of inoculation. The temperature in the animals fell after inoculation in every case but one, in which a temporary rise occurred, and remained from one to three degrees below the nor- mal until death. The streptococci taken from four cases of true diph- theria and from four cases of pseudo membranes in which the Loeffler bacilli were absent were inoculated in rabbits. The temperature of the rabbits rose after inocu- lation, in every case, from one to five degrees. In two local abscess and sloughing of tissue occurred. In three temporary swelling and redness and in three no reaction PSEUDO-MEMBRANOUS INFLAMMATIONS. I 5 appeared. Four died between the fourth and fifth weeks. No streptococci were obtained from either the blood or viscera of the fatal cases. Description of the Willard Parker Hospital. — This hospital is under the control of the New York City Board of Health and to it are sent diphtheria and scarlet-fever cases. The diphtheria wards, in which the majority of the cases here studied were treated, comprise three large, high rooms, connected by a hallway. Two are used for the women and children, and one for the men. As far as possible, the convalescent and doubtful cases are separated from those having true diphtheria ; but owing to the frequently crowded condition of the wards, this often cannot be done. The floors are of hard wood, and are washed daily with i to i,ooo bichloride solution. The iror- bedsteads are carbolized each morning. Where patients soil their beds, the sheets and spreads are changed daily ; in other cases, v/eekly. All patients have their nostrils and throats syringed with a i to 4,000 bichloride; solution, the bad cases every half hour, the convalescents three times a day. No swabbing of throats is allowed. All clothes brought to the hospital are disinfected, and are only returned when patients leave. Patients are also required to take a bath when they go (also, if possible, when they come), washing the hair with a i to 1,000 bi- chloride of mercury solution. Cases of laryngeal dyspnoea when urgent, or when not relieved by vomiting and calomel fumigations, are intu- bated. The only routine constitutional treatment is to give alcoholic stimulants throughout the course of the disease to those showing any tendency to heart failure. Tube cases are fed lying on the lap with lowered head. These details are necessary to show the conditions under which the patients were placed, and to avoid a repeti- tion of the account of the treatment in the clinical histories which follow. The wards for scarlet fever are on a different floor, and have the same arrangement of rooms. Methods of Clinical Study. — I made daily rounds with Dr. Lester, the resident physician ; each case was care- fully observed, the appearance of the throat, and the complicating conditions of the larynx and nostrils were noted. As far as possible sketches were made, and the changes occurring from day to day noticed. The figures for pulse, temperature, and respiration were taken from the hospital charts — the temperature in children being always taken by the rectum, in adults by axilla. The urine analyses were also obtained from the hospital rec- ords. Cultures were made from every case on the day of admission, those which showed very numerous col 1 6 DIPHTHERIA AND ALLIED onies of the Loeffler bacilli were not examined again for three days, and then every other day till the bacilli had twice proved absent. Cultures were made twice from cases of croupous tonsillitis. Those having croupous laryngitis were examined daily, until all doubt as to the presence or absence of the Loeffler bacilli was dispelled, s;vabs and bits of coughed-up membrane being used. The same care was taken in extensive pseudo-membranous inflammations, in which the Loeffler bacilli were absent. During the last six weeks some of the cases were subjected to only one thorough bacteriological examination. True Diphtheria (Clinical histories and bacterial exam- inations of 27 illustrative cases from the 54 in which the Klebs Loeffler bacilli were present). — The aim is to pre- sent in the histories only the most important points. Case I. February 6th. — Molly F , aged five ; membranous laryngitis ; intubation; death. Chnical his- tory : Well nourished ; admitted with marked laryngeal dyspnoea; slight adherent patches on tonsils; no pain on opening mouth ; no swelling of glands of neck. Tempera- ture, 101° F.; pulse, 118; respiration, 34. Vomiting and fumigations not relieving the dyspnoea, she was intubated. February 9th. — Temperature has remained between 100 and loi"^ F. ; pulse and respiration remain about the same. Patient is very languid, and has at times dysp- noea, which is relieved by calomel fumigations. Patches still remain on tonsils. February 12th. — Tonsils clean. Condition unchanged. February i8th. — Temperature normal. Tube re- moved, March 2d. — Patient taken home ; she is weak, can hardly stand, and cannot speak above a whisper. Since the tenth day considerable quantities of albumin have been present in the urine. Considerable emaciation. March nth. — Patient returned for laryngeal dyspnoea, apparently due to laryngeal paresis. She was intubated. March 24th. — Tube removed. Patient is anaemic ; muscles are somewhat atrophied; some albumin per- sists in urine. Remains in bed. March 28th. — Is sitting up and gaining slightly in strength. Returned home. Died two weeks later at home, apparently from nephritis. Bacterial examination : Cover glass smear showed many fairly typical Loeffler bacilh. Plates and tubes showed almost a pure culture of vigorous growing col- onies of the Klebs-Loeffler bacilli. A colony was re- plated, and from this new growth a bouillon tube was inoculated. A guinea-pig inoculated with i c.c. of bouillon culture died in forty-three hours with character- istic lesions. A pure culture of the Loeffler bacilli was PSEUDO-MEMBRANOUS INFLAMMATIONS. 1/ obtained from the tissue at seat of inoculation, while the plates from the heart and organs were sterile. Case II. February 29th. — Harry S , aged two ; intubation ; membranous laryngitis ; recovery. Clinical history : Admitted with marked laryngeal dyspnoea. In- tubation gave complete relief. No membrane visible anywhere in throat. Very slight prostration. Tempera- ture, 101° F. ; pulse, 124; respiration, 32. On sixth day tube was coughed up. Except for the sHght prostra- tion there were no bad symptoms. Bacterial examination : Plates and tubes made from a swab of the throat contained a number of typical col- onies of the Klebs-Loeffler bacilH. Cultures made on following days gave none. Streptococci were always present. Guinea-pig died in forty-eight hours with char- acteristic lesions. Case III. February 20th. — Sarah S , aged four ; intubation ; death. Clinical history : The child had been intubated before admission ; heart irregular and weak ; a few grayish semi-adherent patches on tonsils. Temperature, 100.6° F. ; pulse, 134; respiration, 42. February 2 2d. — Breathing badly, swallows with diffi- culty. Died, 7.15 P.M. Bacterial exammation : Plates show many typical col- onies of Loeffler bacilli, and many of streptococci. Case IV. February 23d. — Benjamin J , aged two years and ten months ; intubation ; death ; extensive mem- brane. Chnical history : Thick, greenish-gray, adherent pseudo-membrane on uvula, anterior faucial pillar and pharynx ; croupy ; glands of neck swollen. Temperature, 101° F. ; pulse, 126; respiration, 38. Very restless. February 26th. — Intubated, with relief of laryngeal dyspnoea. February 27th.— Heart failure and death. Bacterial examination : Plates revealed a great number of active growing colonies of the Loeffler bacilli, and some of streptococci. Guinea-pig inoculated died between forty-eight and sixty hours with characteristic changes. Case V. — Private case, aged one ; intubation ; death ; extensive membrane. Clinical history : Soft, gray- ish, pseudo membranous patches on tonsils, base of uvula, and in nostrils. Temperature, 101° F. ; pulse, 120. Membrane spread slowly over pharynx, and on fifth day invaded the larynx; dyspnoea gradually in- creased ; tissues of neck became greatly swollen ; intu- bated with but slight relief. Died on seventh day. Temperature never above 102° F. Bacterial examination : Many colonies of the Loeffler bacilli and of streptococci. History of infection : Three days before first symp- 1 8 DIPHTHERIA AND ALLIED toms child had been put in a crib for a few hours, occu- pied, two weeks before, by a child who had passed through a dangerous attack of diphtheria. Case VL February 28th. — Rachel M , aged five. Death after disappearance of the membrane. Clinical history : Both tonsils, anterior pillars, left side of uvula, and soft palate covered by a thick, firmly adhesive, grayish pseudo membrane. Dirty discharge from nose. Temperature, 99° F. ; pulse, no; respiration, 24. Apathetic. March ist. — Croupy, relieved by calomel fumigation. Temperature, 99.5° F. March 7th. — Thick membrane has separated. Super- ficial ulceration on faucial pillars and tonsils covered by thick purulent discharge. Since the third the urine has contained large amounts of albumin. Is very weak and apathetic Speaks in whispers and swallows with difficulty. March 15th. — Copious discharge continued, and patient seems unable to swallow or spit it up. Patient suddenly began to breathe with feeble gasps and died at 7.30 a.m. Bacterial examination : Cover glass frorn smear gave an almost pure culture of typical Loeffler bacilli. Cult- ures gave a large number of colonies of the Loeffler bacilli, and a smaller number of colonies of micrococci which appeared as diplococci and in rows of two to eight. After the disappearance of the membrane no more Loeffler bacilli were present, the micrococci above noticed and many other forms replacing them. Guinea-pig died in forty-eight hours with characteristic lesions. Cases 7 to 10 in one family. Malignant diphtheria. Case VIL March 6th. — Cora B , aged twenty- six, the mother ; died. Clinical history : Has been sick five days. Uvula, posterior fauces, tonsils and pharjnx greatly swollen and covered by a very thick, yellow-gray membrane, nostrils occluded by membrane. Lymph- glands hard, slightly swollen. Temperature 100.8° F. ; pulse, 106 and feeble; respiration, 26. Is apathetic, can hardly swallow or whisper. Feels that she is choking. March 8th. — No improvement. Nasal passages ob- structed by thick membrane ; sweetish, offensive odor. Can hardly swallow or spit up the copious discharge. Patient grew worse on the loth. Pulse became imper- ceptible and death occurred at 4 p.m. Case VIII. March 6th. — Maud B , aged five, daughter of last; death after disappearance of mem- brane. Clinical history : Sick for three days. At base of uvula and on tonsils are large patches of thick, yellow- ish-gray pseudo-membrane. Nasal passages occluded by thick, fibrinous membrane. Same odor as from mother. PSEUDO-MEMBRANOUS INFLAMMATIONS. 1 9 Slightly croupy. Patient seemed at first to do well. The membrane gradually separated, and on the nth the throat was clear of membrane. Some ulceration on fauces. On the 14th began to vomit food. This con- tinued on 15th. Heart became weak and patient died at 10 P.M. Case IX. — Clifford B , aged one, son of Cora B ; died. Clinical history : Sick, three days. Pharynx, tonsils, and cavities of nose lined by a thick, offensive, ad- herent pseudo-membrane. Croupy. Patient is cyanotic and septic, and very restless. Died at i.io p. m. Case X. — George B , aged thirty ; father. Clini- cal history : Has had for one day sore throat, pains in limbs, and prostration. ^\Tiole right tonsil is covered by a thick, soft, grayish smear, which can easily be removed, leaving adherent follicular deposits. Slight adherent patch on right anterior faucial pillar. March 8th. — Merely follicular deposits on tonsil and slight membrane on anterior pillar. March 14th. — Throat clean, except small patch on right anterior pillar. March 17th. — Throat clean. Feels well. Bacterial examination : All four cases gave such typical smears on cover-glasses of the Loeffler bacilli that an almost certain bacteriological diagnosis could be immediately made of true diphtheria. Besides the Loeffler bacilli, all had many colonies of a streptococcus which grew rapidly without forming looped colonies. In hanging drop it grew in short chains and as diplococci. The plates showed colonies of numerous other varieties of cocci and bacilli. Guinea pigs were inoculated from cultures of eight and ten. The animals died in seventy-two and twenty-four hours with characteristic changes. The history of the spread of the contagion in these cases is interesting. Two months before, a child living on the floor below them had what the doctor called diphtheria. Until a few days before the sickness of Cora B , the two families had kept apart. For the last few days they had visited each other, and Cora had carried and played with the child who had recovered from the diphtheria. "When the mother took sick she was still allowed to nurse and carry the children. Three days later, the children were discovered to have contracted the disease. The mother, too sick longer to nurse the chil- dren, confided their care to the father, who himself became infected. Antiseptic cleansing of the nostrils and throat was neither used in treatment nor prophylaxis in these cases, before their admission to the hospital. Case XL February 23d. — Charles B , aged thirty; 20 DIPHTHERIA AND ALLIED recovery. Clinical history : Both tonsils, faucial pillars, and base of uvula are covered by a firmly adherent, thick pseudo-membrane of grayish color. Diffuse infiltration of adjacent tissues of neck, February 24th. — Membrane has extended forward over palate. February 27th. — Membrane separating in large pieces. February 29th. — Clean, except for superficial ulcera- tion of mucous membrane of soft palate. On first two days temperature was about 101° F., after that below 100° F. On the tenth day albumin appeared in the urine. Bacterial examination : Cultures made from bits of membrane showed many colonies of the Loefiier bacilli, until the 29th, when they ceased to appear. There were always many colonies of the streptococcus present. Case XII. February 25th. — Gustav V — — , aged twenty-one. Recovery. Clinical history : Thick adherent patches of pseudo-membrane on tonsils and lateral walls of pharynx. Membrane began to peel ofE on the 27th, and had all disappeared on the 29th. After the first day the temperature was normal. Most abundant colonies are of the Loeffier bacilli ; some colonies of streptococci present. After the 29th no more Loeffier bacilli present. Guinea-pig inoculated died in seventy hours, with usual conditions. Case XIII. February i6th. — Mary C , aged twenty ; malignant ; death. Clinical history : Has been sick two days before admission. Tissues of pharynx and palate swollen and oedematous. Whole of uvula, tonsils, part of soft palate, and part of pharynx covered by a thick, adherent, dirty gray pseudo-membrane. Much swelling of tissues of neck. The breath has a foul, sweetish odor. Patient is much depressed. Tempera- ture, 98° F.; pulse, 100; respiration, 28. The pharynx, tonsils, and soft palate became one swollen mass covered by sloughing membrane. Swallowing difficult. For the last two nights patient was delirious and restless. February 20th. — Pulse became rapidly weaker, and death occurred. Bacterial examination : Plates showed many varieties of bacteria, of which the Loeffier colonies comprised about one-third. Streptococci, micrococci, and bacilli were present. Case XIV. March 24th. — Polly K , aged thirty ; malignant ; recovered. Clinical history : Sick two days. Pharynx, tonsils, and soft palate swollen and oedematous. Tonsils, faucial pillars, and part of soft palate covered by a rotten, grayish-green, adherent pseudo-membrane. Great prostration. Temperature, 101.4° F.; pulse, 100; respiration, 20. PSEUDO-MEMBRANOUS INFLAMMATIONS. 21 March 25th. — Condition unchanged. Temperature, 99.4° F. March 29th. — Membrane nearly disappeared. Condi- tion improved. Three children of this patient died. Bacterial examination : Many colonies of the Loeffler bacilli, many of the streptococci and others. Case XV. — Child, aged six weeks ; death ; private practice. Clinical history : On first day small adherent patch on left tonsil and on base of uvula, also a piece of membrane hanging down from naso-pharynx, membrane spread over pharynx, and on third day into larynx. Child died on the fifth day. Glands were never swollen, and temperature did not rise above 99° F. until a few hours before death. The day before the illness of the chDd was noticed the mother was discovered to have diphtheria, and the child immediately removed, but too late. The mother went through a severe illness, also without fever, but recovered. Bacterial examination : An almost pure culture of Loeffler colonies on plates. No streptococci. Animal inoculation : Guinea-pig died in fifty hours, with fairly characteristic lesions. Case XVI. — Child, aged two ; recovery. Clinical history : Adherent gray patches, first on tonsils, then on pharynx and roof of soft palate. On seventh day spread to larynx and caused great dyspnoea. Calomel fumiga- tions given every hour. Child never seemed very ill, except for the dyspnoea. Temperature never above 100° F. Glands not swollen. Bacterial examination : The majority of the colonies were those of the Loeffler bacilli. Numerous colonies of micrococci were also present. No streptococci found. Case XVII. February 13th. — Child, aged six ; pri- vate practice ; recovered. Clmical hi^'tory : When first seen tonsils were swollen. Next day adherent patches seen on tonsils. Tonsils became clean five days later. Some days afterward child was noticed to limp, and slight paresis of muscles of left side was found. In the next house, the week before, there was a case of clinical diphtheria, and this child played with the children from the other house. Bacterial examination : Many colonies of Loeffler ba- cilli and many scattering forms. Case XVIII. April 25th. — Minnie M , aged twelve. Abscess tonsil ; diphtheria. Comes from an asylum from which three others with diphtheria have been received. Has complained of sore throat for two days. Both tonsils and left peritonsillar region swollen and hyperaemic. Adherent patches on left tonsil, fol- licular deposits on right. Temperature, 102° F. ; pulse 22 DIPHTHERIA AND ALLIED 90 ; respiration, 24. Abscess in left tonsil ruptured and discharged a large amount of pus at the moment of ex- amination. Recovered entirely by fourth day. Cultures gave numerous colonies of the Klebs Loefifler bacilli and of long-chained streptococci. Guinea-pig inoculated died in forty-four hours, with characteristic lesions. Plates and tubes from tissue at point of inoculation gave abundant colonies. Case XIX. February, 1892. — Child, aged six weeks; private practice ; death. Chnical history : Began with bloody discharge and membrane in nose. Membrane spread to pharynx, tonsils, and larynx. Death about the tenth day. Father of child had been attending diphtheria cases. Bacterial examination : Cultures from a piece of mem- brane gave abundant colonies of the Loefifler bacilli and of the long-chained streptococcus. A piece of mem- brane taken three days later from the nose gave very numerous colonies of the staphylococcus pyogenes aureus. Guinea-pig died in forty-eight hovus, with characteristic lesions, after inoculation with the bacilli. Case XX. February 13th. — Henry K , aged six- teen. Clinical history : For one week a room-mate had been sick with diphtheria, swabs from whose throat gave an almost pure culture of the Klebs Loeffler bacilli. On first day of his illness both tonsils and adjacent borders of pillars were covered by a thick, soft, dirty pseudo- membrane. The pharynx and fauces were swollen and deeply injected. Temperature, 103° F. ; pulse, 120. Glands swollen. February 14th. — The tonsils still swollen and painful, but the diffuse membrane disappeared, leaving only croupous patches confined to the tonsils. February 17th. — Small follicular deposits still remain. February i8th. — Tonsils clean, though still swollen. There was never any albumin in urine. Temperature and pulse sank to normal on the second day. Bacteria] examination : Very numerous colonies of the Loeffler baclli, some streptococci. Case XXI. March 23d. — Cornelius V , aged seven. Clinical history : Tonsils, anterior faucigl pillars, and roof of soft palate covered by a thick, grayish-white, adherent membrane. Temperature, 101° F.; pulse, 120. Marked swelling in adjacent tissues of neck. Consider- able prostration. March 27th. — Membrane peeling off. Glands of neck less swollen. Temperature, 100° F,; pulse, 130, Pros- tration still marked. March 29th. — Expelled a large piece of membrane from nose. PSEUDO-MEMBRANOUS INFLAMMATIONS. 23 April I St. — Throat clear. Temperature, 98.6° F.; pulse, 130. Made a slow recovery. Bacterial examination : Very abundant colonies of Loeffler bacilli and many streptococci. Case XXII. March 23d. — John V , aged five, brother of previous case. Clinical history : Slight ad- herent patch on left tonsils. Hardly complains at all. Temperature, 100° F. Mirch 25th. — Patch smaller. March 27 th. — Throat clean. Feels well. Bacterial examination : Cover-glasses show many typi- cal Loeffler bacilli, of chain cocci and diplococci. The cultures from both cases contained many colonies of the Loeffler bacilli, streptococci, and micrococci. The previous week the oldest sister had croupous in- flammation of the tonsils and soft palate. The children were not isolated. The second child had absolutely no symptoms. Treatment with spray and douche of i to 4,000 bichloride solution was begun probably a few hours aft^r infection. Case XXIII. February 17th. — Gussie G , aged three and a half ; diphtheritic rhinitis ; recovery. Clinical history : Slight deposits on left tonsil. Obstruc- tion to nasal breathing and dirty discharge from the nose. February 21st. — Small adherent patches still on ton- sils. Glands on left side of neck swollen and painful. February 23d. — Today a large, thick, fibrinous pseudo- membrane, four inches in length, was washed from the nose. It was a partial cast of both nostrils. Patient doing well. Tonsils almost clean. On the 25th scarlet fever developed, from which she finally recovered. Temperature never rose over 101° F. until the development of the scarlet fever. Bacterial examination : From the pharynx the culture showed many typical colonies of the Klebs-Loeffler ba- cilli. From the membrane from the nose only a very few colonies were obtained, among which were a few of the Krebs- Loeffler bacilli and a few of the streptococci. Membranous Rhinitis. — Case I. — January 19, 1892. Roosevelt Dispensary. Service Dr. Jonathan Wright. Aged three. Recovery. Clinical history : Right nostril occluded by a thick succulent membrane. Left shows in front small adherent deposits. Upper lip eczematous with a few pustules. Bloody secretion from nose. Pharynx and larynx free. Temperature by rectum, 100° F,; pulse, rapid. Removal of a piece of membrane caused consid- erable bleeding. Patient never seemed really ill. On the fifth day the nostrils were free from membrane. Still considerable discharge and swelling. No albumin in urine. Bacterial examination : Cover glass preparations from 24 DIPHTHERIA AND ALLIED membrane showed cocci, diplococci, and bacilli, among which were some fairly typical Loeffler bacilli. Cultures contained numerous colonies of Loeffier bacilli and of the long- chained streptococci and of a few other micrococci. Guinea-pig inoculated with i to 2 c.c. of bouillon cult- ure, second generation, of the Loeffler bacilli, died on the fifth day, with characteristic lesions. A rabbit was inoculated in the ear with i to 2 c.c. of a bouillon culture, two days old, of the streptococci. On the sec- ond day rabbit's temperature was 102^ F.; the ear about inoculation somewhat reddened. On third day temperature 103° F., considerable redness and cedema of the whole central half of ear was present. The temper- ature and local signs of inflammation then subsided. Case II. — Gertrude B , aged four. Discharge and occluded nostrils for six days; peevish; ansemic. Both nostrils filled in front by a thick, succulent, adherent, light-gray membrane. Free hemorrhage on removal. Pharynx clear of deposit. Temperature, pulse, and res- piration nearly normal. Urine, 1.007, dear, no albumin or casts. On sixth day membrane separated. Case III. — Tom Mc :, aged four and a half. Van- derbilt Clinic, service Dr Simpson. Discharge and oc- cluded nostrils one week. Both nostrils filled by thin, grayish- white, adherent pseudo-membrare. Tempera- ture, 100° F.; pulse, 130. Urine, i. 010, clear; no albu- min or casts. Nostrils clear sixth day. Case IV. — Ellen B , aged eighteen months. Roose- velt Dispensary. For six weeks has had an otitis media. For one week discharge from nose. On septum and tur- binated bones thin, grayish-white, adherent membrane. Child seeras well. Membrane all disappeared on fifth day. Case V, — E. W , aged five. Same history as previous cases. Membrane separated sixth day. Never appeared sick. Case VI. — Mary B , aged three. Membrane sep- arated sixth day. Never appeared seriously ill. In all the latter five cases of membranous rhinitis quite numerous colonies of the Klebs-Loeffler bacilli were present, in three associated with streptococci, and in two with staphylococci. From the first four, guinea pigs were inoculated. One died on the fifth day and one on the seventh. The other two appeared sick for a few days and then recovered. In the neighborhood of the inocula- tion some induration could be felt. The slight virulence of the bacilli is remarkable. These cases are very interesting. Like those observed by all other observers they ran a benign course. The only precaution to prevent the spreading of the contagion was antiseptic irrigation. No history of infection was ob- PSEUDO-MEMBRANOUS INFLAMMATIONS. 25 tained in any. In all six cases the colonies of the Loeffler bacilli grew rather feebly, both on the blood-serum and on the agar. The bacilli from the agar were small and often pomted, from the blood-serum and broth long and slender, with swollen ends. The cultures died out more quickly than those from ordinary cases. The bacilli in the membrane were rather long and slender, with few clubbed forms. Cases of Laryngeal Diphtheria Requiring Intubation. Name. Age. oi"^ C in " C 2-- s. "' s- « c u P< iH O in H Result. 'Lizzie D . . Maggie D . Margt. G. Lena G. . . Abram A. . 6 Ike S 71 Charles H. 8 Female . . . 9 Female . . . 4yrs. I yr. 4>^yrs. 2>^yrs. 4yrs. syrs. Syrs. 2yrs. 4yrs. 2}^ yrs. I yr. Croupous laryn- gitis. Croupous laryn- gitis : slight patches ton- sils. Croupous laryn- gitis ; tonsils and uvula. Croupous laryn- gitis ; si i ght patches ton- sils. Croupous laryn- gitis ; tonsils. Pneumonia ? Temp., 102 ; pulse, 130 ; rasp., 40. T e m p e ra- ture, 101.6 ; pulse, 118 ; resp., 28. Temp., 10 1 ; pulse, 150 ; • resp., 56. Temp., 102 ; pulse, 140; resp., 42. Temp., 104; pulse, 136 ; resp., 46. Croupous laryn- Temp., 100 ; gitis ; bron chitis. Croupous laryn- gitis ; scarlet fever. Croupous laryn- gitis ; m e a - sles. Croupous laryn- gitis ; tonsils and pharj-nx. Croupous laryn- gitis; slight patches ton- sils. Croupous laryn- gitis. Croupous laryn- gitis. Croupous laryn- gitis ; pharynx and tonsils. Croupous laryn- gitis ; pharynx and nostrils. pulse, 132 ; resp., 30. ;Temp., 103. Reported in his- \- tories of Cases No. 1-5. Intubated 3d day ; died 4th day. Intubated be- fore admis- Tntubated 4th day ; died 6th day. Intubated 4th day ; died 6th day Intubated be- 1 Died, fore admis- I sion ; died next day. I n t ubated on admission. Died. Died. Died. Died. Recov- ered. I n t u bated on admission. Intubated Intubated '. , Intubated . . Intubated . Intubated . . Intubated . . Intubated Recov- ered. Recov- ered. Died. Died. Recov- ered. Died. Died. Died. Whole number of cases requiring intubation, 14, of which 10 died and 4 recov- ered. Ages varied between one and five years. In Case 8 the bacilli grew and appeared like those in the membranous rhinitis cases. In 6 of these no membrane was visible anywhere above the larynx. In i scarlet fever, and in i measles ex- isted as a complication. 26 DIPHTHERIA AND ALLIED Table of Diphtheria Cases not Included in the List of Cases of Mejnbranous Rhinitis and Laryngitis. Age. Location of Pseudo-membrane. s 3 Tonsils. Oi Nose and phar- ynx. X a >. S , i-l- B 3 Q Result. I 2 3 4l s' 6 F. M. F. F. F. F 6 years. 4 years. 6 years. 12 years. 10 years. 4 years. 4 years. Follicular de- posits. Patches Patches Patches l* ollicular . . . Patches Patches Patches Patches Patches Patches Patches Deposits .... Follicular .... Patches Follicular Extensive .... Extensive.. . . Extensive Extensive Extensive . . . Extensive Extensive. . . . Extensive .... E.xtensive .... Slight Slight Slight Slight Extensive. . . . Extensive . . . Extensive. . . . Slight Slight I I Days. 6 4 4 4 5 4 4 5 6 5 4 6 5 8 Recovered. Recovered. Died. Recovered. Recovered. Died. 7i M. 8 F. Died. g; B'. 1 6 years, lo; v. • IS years. II F. i6 years. 12, M. 21 years. 13 F. 4 years. 14 F. I 6 years. I Died. I •• Died. Recovered. Recovered. 16 17 18 19I 20 21 22 23 24 25 26 27 F. 4 years. 5 years. 26 years. 5 years. I year. 30 years. 30 years. 21 years. i 20 years. 30 years. i 6 weeks. j 2 years. I 6 years. Syear.s. 6 weeks. 16 years. 7 years. S years. 5 months. I I I I I Ptiarynx Naso-pharynx. . I I I I 1 8 15 7 9 4 10 6 4 6 7 5 Died. Died. Died. Died. Died. Recovered. Recovered. Recovered. Died. Recovered. Died. Recovered. 29 30 31 32 33 34 I Recovered. Died. Died. Naso-pharynx. . Naso-pharynx . . I" Recovered. Recovered. Died. Resume of Points of Interest in the Fifty -four Cases of True Diphtheria. (The reliability of cultures and of the immediate diagnosis from cover glass smears.) — In every case in which cultures revealed the Loeffler bacilli during any part of the disease the first examination dis- closed numerous colonies. This would seem to show that cultures made from a fresh swab, or bit of mem- brane, can be thoroughly relied upon to show the presence or absence of the Loeffler bacilli as soon as the pseudo- membrane is developed. After the complete separation of the membrane they were in every case missed. In many cases an examination of cover-glass smears, when made from fresh swabs or membrane, gives an immediate reliable diagnosis. This requires great care and should always be controlled by cultures. Swabs from the pharynx of cases, in which no membrane was visible, also give knowledge of the bacteria infecting the larynx. PSEUDO-MEMBRANOUS INFLAMMATIONS. 2/ Methods of Spreading the Contagion. — Cultures made from the dried stains on spreads, pillow-ca'^es, and sheets, where soiled by the expectoration of diphtheria patients, showed, in every case, at least a few colonies of the Loeffler bacilli. (See Photograph 4.) We know by actual experiment that, under favorable conditions, when mixed with shreds of tissue and mu- cus, they live for many weeks. The sputum of patients, though apparently not containing any bits of membrane, is yet usually crowded with them. More than one third of the cases gave a clear history of having been brought in contact with the persons or clothes of those suffering from, or having recently had, severe pseudo membranous inflammations, diagnosed as diphtheria ; and in eight the diagnosis had been verified by finding the Loeffler bacilli. Case V. brings out strongly the manner in which diph- theria breaks out in unexpected places. The child, aged five, is taken out of town and left to sleep in an infected bed for a few hours, and dies ten days later. In another, a child is sent away for safety, but carries with him his infected clothes, and some of his playmates take the dis- ease and die, while he himself escapes. In another, five weeks before there existed diphtheria in the flat below. The first new patient taken sick was a child, aged two and a half years, three days later another, aged four, and then the mother herself. The children died, the mother went to the hospital and finally recov- ered. When she left home, her seven months' baby went to a friend's, where, three days later, two of the children developed diphtheria, and then finally the baby itself. The baby came to the hospital and died, one of the other children died. Cases VII. to X. show the methods of transmitting the disease from one to the other. The sick mother carries the children and infects them. The father cares for them and is himself infected. Physicians certainly are not careful enough to avoid carrying infection in their clothing, and to make sure that those whom they send from an infected house do not take it with them. In several of those in which the history of infection was investigated, great carelessness on the physician's part, in regard to warning those about the sick, was shown. The large number of cases of diph- theria which occur in the families of physicians should lead them to realize the danger of their carrying infection to others. The practice, in hospitals for contagious diseases, of wearing gowns when examining patients, should be par- tially adopted by practitioners. The frequent crowded 28 DIPHTHERIA AND ALLIED condition of the diphtheria wards in the hospital forces the placing in the same room, and often in adjacent beds, those having true diphtheria and those not having it. At first it would seem that the contagion must be car- ried from one to the other, but, as far as the Resident Physician knows, this has not taken place in the last two years, and it certainly never occurred during these inves- tigations. The great attention paid to cleanliness in the wards and the sterilization of instruments of examination ac- count partly for this, but the routine cleansing of the nos- trils and throats of all patients with a weak bichloride of mercury solution has also an important share in giv- ing this freedom from infection. The iiiportant fact is that it seems possible to almost entirely prevent the spread of diphtheria if proper precautions are taken. Age. — Of the 54 cases, 43 were under 10 years; 2 were under 8 weeks ; 1 1 were adults. Mortality. — Twenty-five died out of the 54 ; 4 deaths occurred in the 11 adults; 10 of the 14 cases requiring intubation died. Effect of Treatment. — The patients that died in the hospital were, without exception, those that on admission had either very extensive membrane or laryngeal compli- cations. In only three was there any extension of the dis- ease after irrigation with i to 4,000 bichloride solution had been commenced. In a number of families where different members had had the disease for different lengths of time, those longest sick without treatment did badly, while those just attacked did very well. In these cases the virulence of the bacilli and the family predis- position were the same in both the early and later cases, so that the great difference in the course of the disease in the two classes was probably the effects of the treat- ment. Location of Pse ado-membrane. — Of the 54 cases, in 6 the disease was confined to the nostrils, in 5 to the larynx and bronchi. In all others the tonsils were more or less involved. In bad cases the soft palate and uvula were extensively invaded. In the adults, the pseudo- membrane was generally thick, usually extensive, and of a dirty grayisji color. In bad cases, the membrane became very thick and offensive. In some of the children the mem- brane presented the same appearance as in adults, while in others it was thin and grayish white, often simply in the form of little patches on the tonsils, uvula, soft palate, or faucial pillars. Two cases with true diphtheria from an asylum, one appearing like a follicular tonsillitis and the other with an abscess of the tonsil, bring out the difficulty in making PSEUDO-MEMBRANOUS INFLAMMATIONS. 29 a clinical diagnosis. In most of the mild cases in chil- dren this was impossible. The severity of the disease seems to be almost directly in proportion to the extent of the membrane. The dif- ference in cases is very striking. Those of croupous rhi- nitis, and many in which the disease is confined chiefly to the tonsils and uvula, both children and adults, hardly seem ill at all. Others with throat and nose lined with membrane are very seriously ill from the beginning and usually die. The cause of the great difference in these cases is a very interesting study. It is certainly true that malignant cases usually propagate malignant ones, and mild cases mild ones. It is also true that now and then a severe case has received its infection from a mild one, and more frequently still, mild cases have come from severe ones. The most plausible explanation seems to be that there is a great difference in the virulence of bacilli from dif- ferent cases, and also that the degree of susceptibility of individuals varies greatly. Some seem almost to be im- mune. Whether the greater proportion of children in- fected is due to their greater susceptibility, or to the fact that they are so apt to put things in their mouths, and that, when carried, their faces are brought directly against that portion of the clothing most likely to be infected, is an interesting question. In the limited number of cases here examined the ef- fect of the association of other organisms cannot be safely judged. The opinion has been forced strongly upon me that the Loeffler bacillus is the predominating factor. Some of those having given pure cultures of the Loef- fler bacilli have been fatal, while others in which strepto- cocci abounded have been very mild. In malignant cases with sloughing membrane the surface is crowded with micrococci and bacilli, but the probability is that they find the dead tissue a good soil for their growth. In small children the association of the streptococci probably adds to the danger of a complicating broncho-pneumonia. The temperature has been looked upon as a test by some. It is the general experience of those who have inoculated animals with Loeffler bacilli that the temper- ature falls soon after, and remains subnormal till death. On the other hand, inoculations of streptococci, when they produce any effect, raise the temperature. In those cases of diphtheria in which the bacilli alone were present the temperature never rose above 100° F. In those in which the streptococci were abundant some had a high temperature, others a low. For prognosis the temperature was of no value except in children where lung complications occurred. 30 DIPHTHERIA AND ALLIED The marked swelling of the cervical glands and tissues was present only in those cases where other bacteria, es- pecially streptococci were present. In many fatal cases there was no swelling, while some in whom it was marked recovered. In the bad cases, albumin in large amounts usually appeared in the urine. In many mild cases, no albumin was ever found. The deaths occurring some days after all membrane had disappeared from the throat bring out a peculiar danger in diphtheria. The six cases of membranous rhinitis are of great interest, for it is only very recently that they have been thought to have any relation to true diphtheria. They seem regularly to recover. Pseudo-membraiious Inflammations in which the Klebs- Loeffler Bacilli are Never Present. — These will be con- sidered in the following clinical divisions: i. Extensive pseudo membranes, mostly confined to tonsils, soft palate, and pharynx : a. Uncomplicated ; ^, complicating infec- tious diseases. 2. Pseudo-membranes involving larynx (as only two of these were complicated by infectious dis- eases they will be considered with the uncomplicated cases). 3. Pseudo-membranes confined to the tonsils. Extensive Pseudo 7nembranes, Confined Chiefly to the Tonsils, Soft Palate, and Pharynx. — Case I. February 5, 1892. — Polly D , aged eight. Clinical history : Tonsils covered by large, irregular, adherent, whitish patches. Fauces and tonsils swollen, and livid in color. Temperature, 104° F.; pulse, 40; respiration, 20. February 6th. — Tonsils, sides and tip of uvula, and faucial pillars covered by a thin, friable, grayish pseudo- membrane, which leaves a bleeding surface on removal. The appearance is as if on a mucous membrane denuded of its superficial epithelium a thick paint had been ap- plied. February 7th. — Tonsils and faucial pillars clear of membrane ; superficial ulceration on pillars, and adher- ent membrane to uvula. Temperature remains between 102 and 104° F.; pulse, 118 to 130; respiration, 24 to 30- February i6th. — Ulceration on uvula nearly healed. Temperature normal. No albumin in urine at any time. No great prostration. Bacterial examination : Cultures were made daily from bits of membrane or swab, but never revealed any Loef- fier bacilli. A quick-growing streptococcus which often appeared as a diplococcus was always the most frequent organism present. Case II. February 27th. — Charlotte V , aged nineteen. Clinical history : Both tonsils, and adjacent PSEUDO-MEMBRANOUS INFLAMMATIONS. 3 1 surfaces of uvula covered by a thin gray membrane. Tonsils much swollen and painful. Great hypersemia of pharynx. Temperature, 99.6° F.; pulse, 100. No al- bumin in urine. February 29th. — All symptoms abated. Membrane disappeared. No sw^elling of glands. Bacterial examination : Almost pure culture of strep- tococci growing in long twisted chains. Case III. February 3d. — Rose L , aged sixteen months. Clinical history : Thin, adherent, serai-trans- lucent membrane on tonsils and adjacent surfaces of uvula. Nostrils occluded, but no membrane visible. Croupy voice and breathing. Slight swellmg of glands of neck. Temperature, 100.2° F.; pulse, 136; respira- tion, 34. February 4th. — Membrane nearly disappeared. Child nearly well. February 6th. — Throat perfectly clean. Child is well. Evening temperature, 100° F.; pulse, 118 j respiration, 28. Bacterial examination : Almost pure culture of a streptococcus growing in long chains. A few colonies of a short-chain bacillus. Case IV. March 14th. — George M , aged four years. Clinical history : Five days ago both tonsils re- moved. Now, on depressed stumps of tonsils, on an- terior pillars, and on adjacent surfaces of the uvula is a very thin grayish membrane. Complains of sore throat and not feeling well. March 8th. — Membrane has disappeared. Bacterial examination : Plates and tubes gave a pure culture of a rapid-growing streptococcus, often appear- ing as a diplococcus. Case V. March 25th. — Woman, aged twenty-four. Case from Presbyterian Hospital. History of sore throat and pseudo-membrane for a week. Clinical history : Pharyrx and tonsils swollen and livid red in color. Considerable pain on swallowing. Thin, flaky, whitish pseudo-membrane on the sides of the uvula, extending up a short distance on the soft palate, where the swelling has caused creases of the tissues, also similar-looking patches on the tonsils and pharynx. Temperature range, 100 to 101.5° F. Bacterial examination : Many colonies of the long- chained streptococcus. Case VI. February 6th. — Margaret M , aged twenty months. Clinical history : Uvula and lateral walls of pharynx covered by thin, adherent patches. February 8th. — Still remain on uvula. Temperature varies between 99 and 101° F. February nth. — Throat clean. 32 DIPHTHERIA AND ALLIED Bacterial examination : Cultures reveal many colonies of the long chained streptococcus. This case has an extremely interesting history. The child was exposed to scarlet fever for three hours just before its admission to the diphtheria wards of the hos- pital. On the eighth day the child developed scarlet fever. In two other cases, with similar throats, the chil- dren showed slight desquamation and are therefore con- sidered as complicating scarlet fever. In this case the history excludes such a supposition. Case VII. February 3, 1892. — Gussie G , aged nineteen. Clinical history : Hyperaemia of whole pharynx and tongue. Adherent thin grayish-white membrane on sides and tip of uvula. A few small grayish deposits on left tonsil. Temperature, 101° F. ; pulse, 98. On fifth day, no membrane ; feels well ; sixth day, discharged. Temperature, only on two days above 100° F. On the fourth day, trace of albumin in urine. Bacterial examination : Cultures contained no colonies of the Loeffler bacilli, but many colonies of the long- chained streptococcus. Case VIII. February 3d. — Jennie K , aged eigh- teen. Clinical history : Thin adherent pseudo-membrane on sides and tip of uvula. Some hyperaemia of pharynx. Temperature, 101.4° F.; pulse, 100. Membrane re- mained four days. After the first day, temperature and pulse sank to the normal, and patient did not appear sick. No albumin in urine. Discharged on the sixth day. Bacterial examination : Cultures revealed many colo- nies of the long-chained streptococcus and numerous others of various forms. Case IX. February 2, 1892. — Mary D , aged twenty-one. Clinical history : For the past three days, pain on swallowing and on opening mouth. Posterior half of left tonsil, and post pillar, and most of uvula, covered by a thin grayish-white membrane, easily re- moved, leaving only a few bleeding points. No appre- ciable ulceration. Temperature, 102'' F. ; pulse, 108 j respiration, 26. Glands of neck on left side swollen. February 25 th. — Still thin white membrane on both tonsils and adjacent surfaces of uvula. Bacterial examination : Plates and tubes gave a pure culture of the streptococcus. Five other cases gave histories and lesions so similar to the above that it seems needless to give them in full. Summary. — These fourteen cases present such uniform clinical appearances and histories that they deserve to be considered by themselves. The ages ranged from twenty months to twenty-one years. In no case was any FSEUDO-MEMBRANOUS INFLAMMATIONS. 33 clear history of infection obtained, or of exposure to scarlet fever or measles. The considerable duration, three to eleven days, averaging five days, is important. In these cases there is first a redness and swelling of the mucous membrane of the pharynx, tonsils, and fauces, with later a thin purulent discharge. Cultures at this time reveal very abundant colonies of streptococci. The epithelium of the inflamed mucous membrane, where the irritation is intensified by the contact and friction of ad- jacent surfaces, becomes necrotic, and the denuded sur- face becomes covered by a thin pseudo-membrane, composed mostly of streptococci held together by a small amount of fibrin. The streptococci may also penetrate into the denuded mucous membrane. If one looks at a well marked case, having the patient open the mouth slightly, and depresses the tongue just a little, one will notice the inflamed uvula lying between and against the swollen tonsils. On the portions of the uvula thus irritated by contact, on the faucial pillars lying against the tonsils, and, in extreme cases, on the lateral walls of the pharynx and on the soft palate spreading up from the sides of the uvula, one finds this pseudo mem- brane which is always light grayish in color, thin, and friable. On removal, a bleeding surface is disclosed. When astringent applications are not used, the membrane usually disappears gradually, and does not scale off in firm pieces of considerable size, as in many cases of true diphtheria. In none of these cases was there a fatal result ; neither great prostration, after-emaciation, nor paralysis. Except that these cases were never complicated by suppuration of the cervical glands and diffuse cellulitis, they other- wise appear to be the same as the pseudo-membranous inflammations complicating scarlet fever, the greater severity in the latter being probably due to the influence of the scarlet fever. The temperature curve varied greatly in the different cases. In these fourteen cases the bacteriological diagnosis was of great value in prog- nosis, for pseudo- membranes, so extensive in true diph- theria, would have made it grave. Pseudo-Membranous Inflammations Complicating Scar- latina. — Confined chiefly to tonsils, soft palate, and pharynx. Seventeen of these cases were repeatedly ex- amined. Except for complications, these gave exactly the same clinical appearances as those not complicating infectious diseases. Only six illustrative cases will be given. Case I. February 29th. — James F , aged two and one-half. History of scarlatinal rash. Died. Clmical history : Slight desquamation on hands. There is a thin, 34 DIPHTHERIA AND ALLIED gray, adherent membrane on tonsils. Temperature, 1 00° F. March 3d. — Thin, clean, grayish membrane on sides and tip of uvula. March 7th. — Throat clean. March 15th. — This child, with two others in the ward, to-day showed a re-formation of the membrane on tonsils and uvula. March i6th. — Considerable laryngeal dyspnoea. Mem- brane persists. March i8th. — Intubated. Bronchial rales over chest. Temperature, loi to 103° F. ; pulse, 130 to 150; res- piration, 35 to 60. Broncho pneumonia. March 21st. — Left cheek and lip swollen and oedema- tous. March 23d. — Extensive ulceration of mucous mem- brane of left cheek. Child very weak. Temperature and pulse remain high. March 25th. — Tube removed. Membrane disappear- ing. Less swelling in face. Seems somewhat better. March 31st. — Gradually grew weaker, with continued high temperature, until death. Case IL February 9th. — Frank McM- , aged two. Membranous rhinitis with pharyngitis. Death. Chnical history : Slight membrane on lateral walls of pharynx. Thick, whitish, succulent membrane blocking up both nostrils. Glands of neck swollen. February 12th. — Marked increase in inflammation of glands and periglandular tissues. Pharynx clean. Dis- integrating membrane in nose. February 20th.- — Glands suppurated. Had irregular high temperature, 102 to 105° F. Pulse above 150. Died in septic condition. Bacterial examination : Markedly twisted streptococ- cus, almost in pure cultures. No Loeffler bacilli ever present. Bouillon clear, with flocculent sediment. Case III. February 9th. — Edna K , aged two and one-half. Death. Clinical history : Tonsils, adjacent edges of faucial pillars, and borders of uvula, covered by a thin, pearl-colored pseudo-membrane, which, when removed, reveals ulcerations. Rash. Temperature, 103° F. ; pulse, 156; respiration, 34. Patient died on the 1 8th with high temperature, pulse, and respiration. Bacterial examination : Very numerous colonies of the long-chained streptococci and nearly as many of the staphylococcus pyogenes aureus. Case IV. February 7th. — William W , aged seven. Had had scarlet rash and high temperature. Recovered. Clinical history : On 18th, thin, whitish membrane ad- herent to tonsils. Glands of neck swollen. PSEUDO-MEMBRANOUS INFLAMMATIONS. 35 February 2'jth. — Incision of suppurating glands. Ton- sils clean. February 29th. — Better in every way. Temperature re- mained between 99 to 101° F. Bacterial examination : From throat and from glands a streptococcus, in long twisted chains, was obtained. From the thin purulent serum from the glands a pure culture was secured. Case V. February 23d. — Annie O'H . Recov- ered. Clinical history: Scarlet rash; no fever; slight hypergemia of throat. March 17th. — When apparently well, developed a thin, dirty-white membrane on tonsils, which left a raw surface on removal. March 19th. — Considerable ulceration of tonsils, and marked induration of glands of neck, with tenderness. March 25th. — Membrane disappearing. From swab of throat on February 23d nearly pure cult- ure of the streptococcus longus. From bit of mem- brane, March 19th, almost pure culture of colonies of a streptococcus, appearing as a diplococcus and in short rows under the microscope. Case VI. February x8, 1892. — Rose C , aged three and a half. Died. Clinical history : Child looks very ill. Thin, soft membrane on sides of uvula, an- terior pillars, and lateral walls of pharynx. When re- moved, leaves bleeding, ulcerated surface. Glands of neck swollen. February 21st. — Membrane nearly gone, superficial ulceration on sides of uvula. Glands hard, indurated, and much swollen. Died on 2 2d. Temperature varied between 103 and 105° F.; pulse, 160 to 170 ; respiration, 44 to 58. Bacterial examination : Almost pure culture of the streptococcus. Summary and Remarks. — In 1 1 other cases of similar soft membrane on faucial pillars, edges of uvula, and ton- sils, by far the most numerous colonies were those of the long- chained streptococci. In one case a streptococcus, similar to that occurring in the late membrane in Case v., was present. From 2 cases of follicular tonsillitis, and from 8 cases, without exudation, in which hjper- gemia of pharynx and scarlet rash were present, abundant streptococci were invariably found. In none of the cases were the Loeffler bacilh found. Of the 10 cases of scarlet fever, in which the complicating croupous inflammation appeared early, 6 died. In the 7 in which it appeared late, all recovered. In the 6 fatal cases, 2 had extensive gangrenous cellulitis, beginning in the neck, spreading over the chest, and causing the sloughing of an extensive 36 DIPHTHERIA AND ALLIED portion of skin. A third had diffuse suppuration in and about the cervical glands. The presence of streptococci growing in long twisted chains in the throats of all the cases examined during the period of the eruption is very noteworthy, and strorgly indicates the necessity of carefully looking after the cleansing of the throats, whether any visible membrane is present, or not. The fatal result in some seemed to be due more to the complicating cellulitis and abscesses than to the scarlatina. The possibility, suggested by some observers, that the streptococci may be the cause of scarlet fever, is worthy of investigation. It would take very strong evidence, and necessitate finding some constant differences between the streptococci occurring in scarlet fever and those appearing so frequently in other conditions, or the proof that they can at one time cause scarlet fever and at another a local lesion in the throat. It would seem more probable that the mfec- ' tious diseases, especially scarlet fever and measles, favor the development and growth of the streptococci, known to be so frequently present in both the healthy and in- flamed throat. In three of the children who were entirely convalescent the pseudo-membranous inflammation seemed to be the result of an infection from others in the ward. The pseudo-membrane hning the nasal cavities in Case II. is interesting, indicating that some cases of membranous rhinitis are due to streptococci. Pseudo-metJibranes Involving Larynx causea by Strepto- cocci. — Case I. February 13th. — Hattie S , aged five. Recovered. Clinical history : On admission, cyanotic from laryngeal obstruction; intubated, relieved; very slight, adherent, thin, pearl-gray patches on uvula. Tem- perature, 100° F. ; pulse, 102; respiration, 22. February 17th. — Patient never seemed sick; exudation on uvula disappeared ; no albumin in urme ; tube re- mained in five days. Bacterial examination : Plates and tubes, made on two days, showed no Loeffler bacilli, but many colonies of a long chained streptococcus and scattering forms. Case II. February 14th. — Nochem E , aged six. Recovered. Clinical history : Admitted with marked laryngeal stenosis ; intubation gave perfect relief ; no membrane visible. Temperature, 101° F.; pulse, 132; respiration, 34. From time to time some difficulty in breathing, which was relieved by calomel fumigation. For one week temperature varied between 99 and 101° F. ; pulse, 100 to 126. Never any visible membrane. No albumin. Tube removed on the fifth day. Bacterial examination : No Loeffler colonies found on PSEUDO-MEMBRANOUS INFLAMMATIONS. 37 plates or tubes made from swabs of pharynx and tonsils taken on the first three days ; numerous streptococci. Case III. March i6th. — Osthof , aged three and one half. Recovered. Clinical history : Admitted with marked laryngeal dyspnoea ; vomited, was fumigated, but without relief ; intubated ; both tonsils covered by a nearly white, thin, adherent membrane. Temperature, ioi° F. ; pulse, 128 ; respiration, 30. March 19th. — Still extensive patches of same mem- brane on tonsils ; breathes fairly well ; no prostration. On second day temperature reached 103° F. Now 99° F. Bacterial examination : Numerous colonies of strepto- cocci ; none of Loeffler bacilli. Case IV. March i8th. — Esther F , aged one. Recovered. Clmical history : Very small white patch, slightly adherent to right tonsil ; laryngeal dyspnoea ; made to vomit, and fumigated with calomel, but without relief ; intubated five hours after arrival. Temperature, 99.6° F. ; pulse, 120; respiration, 30. March 20th. — Seems about well ; tube still retained ; some albumin in urine. March 26th. — Tube removed ; temperature never above 100° F. Bacterial examination : Cultures gave abundant col- onies of the long chained streptococcus. Case V. March i9ih. — Morris G , aged four. Died. Clinical history : Intubated before admission. Temperature, 100° F. j pulse, 130; respiration, 32. No membrane visible in throat ; some white, flaky mem- brane conghed up ; large amount of albumin in the urine. March 22. — Chest full of rales; child drowsy and cya- notic, although there is no laryngeal obstruction. Tem- perature, 102° F. ; pulse, 150; respiration, 42. Swal- lows with difficulty. Died on 23d. Bacterial examination : Abundant colonies of long- chamed streptococcus and many of micrococci and other scattering forms. Case VI. March 21st. — Margaret F--^ — , aged four. Clinical history: Marked laryngeal dyspnoea on arrival, intubated one-half hour later ; large piece of thin, crum- bling membrane coughed up through tube ; swollen ton- sil^, with small whitish patches. Temperat;ire, 99 4° F.; pulse, 104 ; respiration, 26. March 24th. — Tube removed; seems well; highest temperature, 101° F. No albumin in urine. Bacterial examination : Cultures from swabs and from membrane coughed up had many colonies of long- chained streptococci and some of streptococci appearing in short rows and as diplococci. Case VII. March 30th. — Katie F , fifteen 38 DIPHTHERIA AND ALLIED months, sister of last. Clinical history : Five days before admission slight cough, next night awoke suddenly with croupy cough. The laryngeal symptoms increased from night to night. Intubated shortly after admission. Tem- perature, 100.2° F. ; pulse, 112; respiration, 28. Thin whitish deposits on tonsils. April I St. — Had an attack of marked laryngeal dysp- noea, requiring the removal of the tube. Attached to it was a long piece of membrane. Temperature, 103° F. ; pulse, 144; respiration, 30. Restless. Patient developed broncho -pneumonia. Temperature remained high. Tube was removed on the eighth day. Died on April loth. Bacterial examination same as in last. These two cases occurring in the same family, one eight days after the other, pomt to the possibility at least of a direct transmission of the contagion. Case VIIE. March 3d. — Jennie P , aged eleven months. Intubation. Death. Clinical history : Slight patches on tonsils, laryngeal dyspnoea. "Whole lower face badly burned, through attempt of mother to give it steam inhalations. Child looks badly. Moist rales over whole chest. Glands of neck slightly swollen. March 4th. — Intubated. The tube keeps clogging with thick purulent fluid. Dyspnoea increased, and child died at midnight. Bacterial examination : From first day many strepto- cocci, and many colonies of a quick-growing micrococcus, which liquefied gelatine and coagulated milk. The growth on the media was entirely different from the staphylococci. From trachea, after death, an almost pure culture of the micrococci was obtained. Case IX. March 17th. — James F , aged two and one-half. Intubation. Death, Clinical history : On ac- count of a previous history of scarlet fever, this case has been described under the scarlatinal class. Case X. March 19th.— William M , aged thirty. From Presbyterian Hospital. Clinical history : No spe- cific, alcoholic, or nephritic history. Symptoms began on the morning of the day admitted. When admitted, pa- tient was suffering from laryngeal dyspnoea. Examination revealed much swelling and redness of whole larynx, also a small patch of moist membrane on arytenoids. March 21st. — Dyspncea was so bad on the 20th as to nearly call for tracheotomy. To-day breathing eas er. Soft, dirty-gray membrane persists on swollen arytenoids. Small patches, also, on the false cords and epiglottis. Membrane disappeared after two days, and patient re- covered. The orderly who attended the patient devel- oped a marked follicular tonsillitis. In both these cases PSEUDO-MEMBRANOUS INFLAMMATIONS. 39 the most numerous colonies were those of the strepto- coccus growing in long twisted chains. Case XL April 27th. — Andrew I , aged forty- three. Death. On admission the history is obtained from friends that he has been three days sick. He is weak, sightly delirious, and appears as if suffering from some severe infectious disease. The whole uvula and the portions of soft palate adjacent to it are covered by a very thin, dirty covering which can hardly be called a pseudo-membrane. ■ The whole pharynx and palate are extremely hypergemic. Patient is hoarse, and has some laryngeal dyspnoea. Temperature, 103° F. ; pulse, 128; respiration, 26. Patient became violently delirious, and died the next day. No autopsy. This case is mteresting as it is the only fatal one in adults. It IS probable that the croupous inflammation was only a complication of some one of the infectious diseases. Pseudo 7?ievibranous Laryngitis, not True Diphtheria. — Table of Cases. ure, and .tion ;al. 3 Name. Age. Disease and g ..h'C complications. g__^ g- b Length of time intubated. Result. i p 3 I) c 1 g 0.- 1 H I Hattie S. 5 Croupous laryn- Temp., 100 ; Membrane re- Recovered. years.] gitis; croupous ' pulse, 102 ; m a i n e d 4 patch on uvu- : resp., 22. days ; i ntu- la. 1 baied for 5 days. a Nochem E 6 Croupous laryn- Temp., loi ; Tube removed Recovered. years. gitis. pulse, 132 ; 1 r^p., 34. 5th day. 3 Harry 0. 33^ Croupous laryn- iTemp., loi ; Tube removed Recovered. years. gitis; croupous 1 pulse, 128 ; tonsillitis. resp., 30. Sth day. 4 Esther F. I Croupous laryn- iTemp., 99; Tube removed Recovered. year. gitis: croupous ! pulse, 120; tonsillitis. i resp., 30. Sth day. 5 RosieB.. sX Croupous laryn- Temp., 99 ; Tube removed Recovered. years. gitis. pulse, 1 16 ; resp., 24. 3d day. 6 Morris G. 4 Croupous laryn- Temp., 102 ; Intubated be- Died. years. gitis ; broncho- pneumonia. pulse, 150 ; resp., 42. fore admis- sion ; lived 4 days. Intubated with 7 Jennie P . II Croupous laryn- Temp., 103 ; Died. mos. gitis; croupous pulse, 150; but slight re- 1 n s ill i tis ; resp., 40. hef ; lived i scald of face ; day. bronchitis. 8 James F. years. Extensive pseu- do- membrane in throat; cellu- litis ; croupous la ry n gi tis ; broncho-pneu- monia. Temp., 100. 19 days after admission in- tubated ; re- moved after 7 days. Died. 9 Barney S. 2>!r Croupous larjm- T e m p e ra- Intubated ; re- "Recovered. years. gltis ; devel- , ture, 101.4; mo ve d 8lh ■ oped measles pulse, 106 ; day. 8th day. resp., 38. 40 DIPHTHERIA AND ALLIED Pseudo-membranous Laryngitis, not True Diphtheria. — Table of Cases. — Continued. -r-o a .' S3 -6 Name. Age. Disease and complications. Temperaturf pulse, an respiratio on arrival. Length of time intubated. Result. ^ lO Wm.C... 2 Croupous laryn- Temp era- Intubated ; re- Recovered. years. gitis; croupous rhinitis. ture, 101.4; pulse, 128 ; resp., 38. moved 8th day. 11 Bert. P . . 4 years. Croupous laryn- gitis. Temp., 104 ; pulse, 144 ; resp., 48. Intubated. Recovered. 12 KateF... 15 Croupous laryn- IT e m p e ra- I n t u b a ted ; Died. mos. gitis; croupous | ture, 100.2; lived II days. t n s i 1 1 itis ; pulse, 112 ; broncho pneu- resp., 28. monia. 13 Margt. F. 4 Croupous laryn- Temp. 99.4; Intubated half Recovered. years. gitis; croupous tonsillitis. pulse, T04 ; resp., 26. an hour after a d m i ssion ; removed af- ter 3 days. 14 Harris A. 3 Croupous laryn- Temp. loi ; I n tubated on Transferred years. gitis. pulse, 144 ; resp., 40. a d m i ssion ; removed 6th day. f r mea- sles 9th day. \ « i| IS Wm.F.. 30 Croupous laryn- Moderately Marked dysp- Recovered. years. gitis. high tem- perature. noea. 16 Andrew J. 43 Croupous laryn- Temp., 103 ; Patient died in Died. years. gitis ; pharyn- gitis, etc. pulse, 128 ; resp., 26. 24 hours ; ap- parently had s m e _ infec- tious disease besides crou- pous inflam- mation. Fourteen of these 16 vi^ere in young children. In 5 of the 16 no deposit or membrane was visible above the larynx. Four of the 5 deaths were due to lung compUcations. Summary. — These sixteen cases, occurring in four months, prove that membranous croup is frequently an independent disease, having no connection with true diphtheria. In only two was any connection with scarlet fever or measles discovered. On admission, a diagno- sis from clinical history and appearance was impossible. In the majority of the ten cases that recovered, the course of the disease was mild After intubation had re- lieved the dyspnoea, the patients never appeared danger- ously ill. By the third day they were sitting up in their beds and plajing with their toys. The temperature aver- aged somewhat higher during the first days than in the cases of laryngeal diphtheria, and rose to 103 and 104° F. when the lungs became involved. In two of the children a pretty clear history of direct infection from other cases was obtained. In croup, the magical effect of intubation is seen, for without trache- PSEUDO-MEMBRANOUS INFLAMMATIONS. 4 1 otomy or intubation the majority would certainly have died. The good percentage of recovery, 71 J per cent., in these cases, as contrasted with intubation m diphthe- ritic laryngitis, 28^ per cent., throws much light on the problem why at certain times and in certain countries the percentage of recoveries is so much greater than in others. It also forces the query whether, m the future, all cases should not be examined bacteriologically, if the statistics are to be valuable. Broncho pneumonia seems to be the most frequent cause of death. Pseudo - membranes Confined to the Tonsils Caused by Streptococci. — Case I. March 3, 1892. — Genet M^ , aged six. CUnical history : From an asjlum with three other cases. Right tonsil is swollen and covered by a thick, adherent, gray-colored, fibrinous pseudo-membrane. Cervical glands considerably swollen on right side. Slight pain and tenderness. Temperature, 101° F. March 5th — Still thick membrane on tonsil. Nowhere else. Feels well. March 7th. — Tonsil clean. Is slightly croupy. March 9th. — Perfectly well. Bacterial examination : Cover-glass made from smear of membrane showed very numerous cocci in pairs, sin- gly, and in chains. Also a few bacilli. Plates gave an almost pure culture of the long-chained streptococcus. Nothing found in anyway similar to the Klebs-Loe filer bacillus. Case II. — Mark C , aged four. From same asy- lum. Clinical history : Pseudo-membrane on upper por- tion of left tonsil and adjacent surface of anterior and posterior pillars. Well on third day. No fever. Bacterial examination : Mostly streptococci. Case III. March 5, 1892. — Lottie E , aged twenty-one. Clinical history : Both tonsils are nearly covered by irregular, semi-adherent pseudo-membranous patches. Considerable swelling and hyperaemia. No swelling of glands. Not much pain ; slight constitutional symptoms. Temperature, 101° F. March 7th. — Tonsils nearly clean. Feels well. March 8th. — Perfectly well. Bacterial examination: Many colonies of the long- chained streptococcus and other scattering forncis. Case IV. March 12th. — Charles F , aged thirty. Clinical history : Two days ago felt pain and soreness in region of tonsils. Went to Bellevue, and was sent to Charity Hospital. From there taken to the Willard Parker Hospital. Both tonsils covered by a dirty- brownish smear which is readily removed, leaving ir- regular patches on tonsils. Pharynx covered by thick, purulent discharge. Tonsils and peritonsillar tissues are 42 DIPHTHERIA AND ALLIED much swollen, and the whole pharynx and fauces hyper- £emic. Considerable swelling of glands of neck. Tem- perature, 102° F. Great pain on swallowing and on open- ing mouth. iMarch 14th. — Still considerable swelling and hyperae- mia, but membranous deposits have nearly disappeared. Feels much better. Bacterial examination : Reveals mostly colonies of the long-chained streptococcus. Case V. March 13th. — Mary C -, aged four. Clinical history : This child is from the same asylum in which four cases occurred ten days before. Both tonsils are swollen, and covered by thick masses of exudate. Temperature, 101.4° F. March i6th. — Tonsils are clean. Patient feels well. Bacterial examination : Plates give nearly pure cultures of the long-chained streptococcus. Case VI. March 14th. — Annie E , as:ed six. Clin- ical history : Both tonsils covered by irregular patches of pseudo membrane, with intervening portions smeared with purulent discharge. Considerable swelling of ton- sils. Almost no constitutional disturbance. March i6th. — Tonsils almost clean. Bacterial examination : The great majority of the col- onies are of streptococci. Case VII. March 7th. — George M , aged thirty- one. Clinical history : Felt chilly and depressed two days ago. The next day his physician on examination found the tonsils swollen and covered with a semi-adher- ent soft deposit. He was referred to the Board of Health. The first examiner thought it a doubtful case, referred it to a second, who pronounced it true diphthe- ria. On admission, condition the same. Glands of neck somewhat swollen. March 8th. — Throat is clear, and he feels well. Bacterial examination : Majority of colonies, strepto- cocci in long twisted chains. Case VIII. March nth. — Lahd F , aged twenty- two. Clinical history : History of recurrent attacks of sore throat similar to present one. Swollen, irregularly excavated tonsils, with a few irregular, gray deposits. Pain on swallowing and opening mouth. March 14th. — Right tonsil nearly covered by dirty ad- herent pseudo membrane. Left, follicular deposits. Less pain and tenderness, March i6th. — Still small deposits on tonsils. March iSth. — Tonsils clean. Bacterial examination : The most numerous colonies are of a rather quick growing streptococcus which occurs as a diplococcus and in short chains of diplococci. PSEUDO-MEMBRANOUS INFLAMMATIONS. 43 Simwiary. — This disease is so familiar that it is unnec- essary to give more illustrative cases. In the 159 here studied 58 are included under this heading. This com- paratively large number would seem to indicate that in adults, thick croupous patches, adherent or not adherent, if confined to the tonsils, after twenty-four hours very rarely h'kve anything to do with true diphtheria. The same bacteria (the streptococci) which under certain in- fluences cause an inflamed throat or a follicular tonsillitis, under others seem to produce a croupous tonsillitis. In several cases two members of a family were affected, one with the former, the other with the latter disease. In a few others a very complete history of direct transmission of the contagion was obtained. The croupous deposit, or pseudo membrane, lasted from two to seyen days. All cases recovered without complications. The intimate connection of some cases of croupous tonsillitis with scarlet fever is brought out in the follow- ing examples : Rose F , aged twenty- one, was admitted, with marked croupous tonsillitis with constitutional and local symptoms, on May 20th. The three previous days she had taken care of a child sick with scarlet fever, and on the last day also of the mother, who was attacked with croupous tonsillitis. Both she and the mother had come in frequent direct contact with the child. Two physicians attended a gentleman sick with malig- nant scarlet fever and croupous tonsillitis. Both were attacked with croupous tonsillitis, and one with scarlet fever also. The streptococci, found in the pseudo-membranes, pre- sented some striking differences. By far the most fre- quently present was a streptococcus showing similar morphological and biological traits to the streptococcus pyogenes and erysipelatus. This streptococcus was pres- ent in all the scarlatinal cases during the eruption. From the different cases the cultures presented some minor differences in the size of the colonies and the ap- pearance of the flocculi in the broth. The pathogenic qualities varied greatly. Inoculations in rabbits from some produced abscess and necrosis, from others merely slight redness and swelling. During the last two months, cultures from a number of cases presented a coccus which formed larger colonies than the long-chained streptococcus on the agar plates, producing colonies with nearly even edges, of a coarse, granular, and blotched appearance. Here and there, from their edges short runners sprouted out, and in some cases short twisting loops. In bouillon, at 37° C, the growth of this streptococcus 44 DIPHTHERIA AND ALLIED is vigorous, forming, in twenty- four hours, considerable gray sediment, with cloudy bouillon. Microscopical ex- amination reveals diplococci in pairs and short rows of four to eight. In gelatine tubes the growth does not differ from that of the streptococcus pyogenes except in that it is somewhat more vigorous. The few animal ex- periments made indicated it to be less pathogenic than the long chained streptococcus in rabbits. Injected in the ears of rabbits it produced redness and swelling, from the second to the fifth day, with very slight or moderate fever. The rabbits after the fifth day seemed well. In- travenous inoculation was without effect in two cases. A third variety differed only from the first, in that the loops were less twisted. One of these forms, usually the first, was the most abundant micro-organism present in everv one of the cases examined, in which the Klebs- Loeffler bacilli were absent. And in cases of true diph- theria they were usually present in greater or lesser num- bers. The staphylococcus pyogenes aureus was only irregu- larly present in the cases examined, and only abundant in five. In these, from the blood-serum tubes alone one would have judged that they were the most abundant form of bacteria, but an early inspection of the plates under the microscope revealed the tiny colonies of the streptococci to be present in far the greater number. In those cases in which suppuration of the cervical glands and extensive cellulitis was present, the long- chained streptococci were always found, except for such complications the special form of streptococci present seemed to exert no influence on the severity or length of the disease. G-eneral Summary. — Bacteria. — In 159 cases of pseudo- membranous inflammations there were 54 in which the Klebs-Loeffler or diphtheria bacilli were present, usually as the only or most numerous form of bacteria. With them were often associated streptococci and other micro- organisms. In every one of the remaining, streptococci were the most abundant bacteria, and often the only ones. From various pseudo membranes the streptococci obtained differed in manner of growth and pathogenic action. The staphylococci were often entirely absent, at other times present in moderate numbers, but never in excess of the streptococci. Location of Lesion. — In both diphtheria and pseudo- diphtheria the pseudo-membranes occurred on the mu- cous membrane of the nose, pharynx, larynx, soft palate, and tonsils. In both, the tonsils were the parts most frequently involved. The nasal cavities were more often involved in true diphtheria. PSEUDO-MEMBRANOUS INFLAMMATIONS. 45 Mortality. — In true diphtheria, 46^ per cent.; in pseudo- diphtheria, 5f per cent.; intubation in diphtheria, 71^ per cent.; intubation in pseudo-diphtheria, 28^ per cent.; adults in diphtheria, 36 per cent.; adults in pseudo- diphtheria, 2 per cent. Contagiousness. — In quite a large proportion of cases evidence was obtained of the direct spreading of diph- theria through contact with infected persons and cloth- ing. In only a few cases of pseudo-diphtheria was equally strong proof obtained. Children sent away from diphtheria for safety, carrying with them their infected clothing, were in a number of cases a source of danger to the families who received them. Clinical Observations. — It is important at the outset to remember that true diphtheria is frequently associated with pseudo diphtheria, and this mingling of the two adds greatly to the clinical difficulties. Severe uncomplicated pseudo membranous laryngitis may be either true or pseudo diphtheria. The early clinical diagnosis is usu- ally impossible. Low temperature, great prostration, and heart failure point to true diphtheria. A high tem- perature, lung complications, and no history of infection are in favor of pseudo-diphtheria. Death occurred usually early, due to heart failure in diphtheria ; usually later, due to broncho-pneumonia, in pseudo-diphtheria. In both, early death from suffoca- tion may occur, if intubation or tracheotomy is not per- formed. Membranous rhinitis is usually a very mild form of diphtheria having a good prognosis. Membranes com- plicating scarlet fever are seldom true diphtheria. Pseudo membranes and thick deposits well developed on, but confined to, the tonsils of adults are nearly al- ways pseudo-diphtheria. Folhcular deposits confined to the tonsils in adults are probably always pseudo-diph- theria. Small or large, thick or thin, firmly or slightly adherent patches confined to the tonsils or extending to the larynx in young children may be either true or pseudo-diphtheria, and the clinical diagnosis is often im- possible during any time of the disease. Extensive thin, grayish pseudo-membranes, occurring only on those sur- faces of the uvula, tonsils, and faucial pillars which lie in contact were always pseudo-diphtheria. The prognosis is good in these cases, except v/hen there are early com- plications of infectious diseases. The thick grayish or grayish-yellow pseudo-membranes which cover a large portion of the soft palate and tonsils, often involving naso-pharynx and nostrils, were always the lesion of true diphtheria. These cases were often fatal in both children and adults. 46 DIPHTHERIA AND ALLIED Conclusions. — The results of previous investigations, with the addition of that brought out in these studies, seem to force on us the conclusion that there are two great divisions of pseudo-membranous inflammations, one caused by the Klebs-Loeffler bacilli and the other by some form of streptococci. The few cases in which the pneumococcus of Fraenkel or other cocci seem the cause naturally fall in the second division. The first is, from beginning to end, a local process, and its lesions are due to the effects of the poison formed by the bacilli in the pseudo membrane. It is dangerous at all periods of life. The second is also at first a local lesion, but may at any time become a general infection. It is peculiarly liable to cause broncho-pneumonia in chfildren. Both diseases are frequently associated to- gether. Both are directly contagious, though in different degrees. These two diseases, caused by different bacteria and differing in so many points, should no longer be called by the same name. The name diphtheria will probably be agreed upon by all for those cases in which the Klebs- Loefiler bacilli are present, whether alone or associated with other bacteria. For the second division some name will have to be agreed upon ; whether the streptococcus will be found to be in such a majority the cause that the name strepto- coccus diphtheria can be applied to it, only further inves- tigation can determine. Perhaps at present the term pseudo-diphtheria will be acceptable. In all cases where the diagnosis is in doubt, bacterio- logical examination should be made, because : 1. A correct diagnosis should always be sought for. 2. Without it, all attempts to learn from statistics the worth of special forms of treatment and methods of pre- vention are well-nigh useless from the frequent incor- rectness of the diagnosis. The fact that during four months less than one-third of the cases sent to the diph- theria wards of the hospital had true diphtheria, is sufii- cent proof of the difficulty of making a clinical diagnosis. 3. It is a great help to prognosis and rational treat- ment in the more severe cases and enables us to take measures more effectually to prevent the spread of the contagion. 4. It is certain, can frequently be made immediately, and always within twenty hours. The amount of familiarity with bacteriological work and the appliances necessary, although not very great, are still enough to prevent the great majority of physicians from undertaking it themselves. As the early detection of diphtheria is important for the general health, and as PSEUDO-MEMBRANOUS INFLAMMATIONS. 4/ this disease occurs most frequently and is most danger- ous among the crowded poor, who are unable to pay for special examination, it would seem peculiarly the business of the Boards of Health to undertake it. In small cities some central place could be selected where the neces- sary appliances could be kept, in large cities several would be necessary. From these laboratories a properly equipped man could be called to make the cultures and give the bacteriological diagnosis. Children's hospitals and those for infectious diseases should certainly give their pathologist the means to do this. To insure the safety of those not having diphtheria, these hospitals should have wards separated, where doubt- ful cases could be kept for twenty-four hours until the diagnosis was made certain by bacteriological examma- tions. Where this is impossible, experience at the Wil- lard Parker Hospital has shown that general cleanliness and antiseptic irrigation of the nasal and pharyngeal mu- cous membranes is sufficient in the great majority of cases to prevent the spreading of diphtheria. Care should be taken not to expose small children to pseudo-diphtheria, for it is undoubtedly contagious under favorable condi- tions and is in them dangerous. I wish, in closing, to express my gratitude to Professor T. Mitchell Prudden, Director of the Pathological La- boratories of the College of Physicians and Surgeons of Columbia College, New York, for his kindress in making many valuable suggestions and in affording me every needed laboratory facility for these investigations. I also wish to thank Dr. T. W. Lester, Resident Phy- sician to the Willard Parker Hospital, for his help in the clinical part of these studies, and for the use of the hospi- tal charts. 128 West Eleventh Street, July i, 1892. References. 1 Loefifler : Deutsche Med. Wochenschrift, 1890, Num. 5 und 6. 2 Welch : Medical News, May 16, 1891. 3 Klebs : Verhandl. des zweiten Congress f. Inn. Med., 1883. 4 Loeffler : Mitth. a. d. Kais. Gesundheitsamte, Bd. 2, 1884. ^ Roux and Yersin : Annales de I'lnst. Pasteur, ii. , 1888, p. 629; iii., i88g, p. 273 ; iv., 1890, p. 384. 6 Kolisko and Paltauf : Wiener klin. Wochen., 1889, No. 8. "< Ortmann : Berlin klin. Woch. , 1889. No. 10, p. 18. 8 Zarniko : Centralbl. f. Bact. , vi., 1889, p. 154. 8 Escherich : Centralbl. f. Bact., vii. , 1890. 1" Beck : Zeitschrift f. Hygiene, viii. , 1890 ; Heft 3, p. 434. i','-Brieger and Fraenkel : Berlin, klm. Wochen., 1890, Num. 11 und 12. " Tangl : Centralbl. f. Allg. Path, und Path. Anat., 1890, Bd. i, P- 795- '■' Babes : Zeitschrift fiir Hygiene, Bd. 5, p. 177. 16 D'Espine : Revue medicale de la Suisse ro., 1888, No. i, p. 49. i« Klein: a, Centralbl. f. Bact., vii., 1890, No. 17; 5, Centralbl. f. Bact., vii., 1890, No. 25. 48 DIPHTHERIA. 17 Welch and Abbott : Bulletin of the Johns Hopkins Hospital, February-March, 1891. '8 Prudden : Medical Record, April 18. 1891. 1^ Roux and Yersin-: Annales de I'lnstitut Pasteur, iii. , 1889, p. 273. 20 Fraenkel and Brieger : Berlin, klin. Woch., December 3, i8go. 21 Babes : Virch. Archiv., Bd. 119, S. 468. 22 Welch and Flexnor i Bulletin of the Johns Hopkins Hospital, August, 1891, March, 1892. 23 Behring and Wernicke : Zeit. Hygiene u. Infect. Krank. , Bd. 12, H. I, S. ID. 2* Brieger, Kitasato, and Wasserman : Zeit. Hyg. u. Inn. Krank., Bd. xii., H. I, No. 2. 25 ibid. 28 Barbier : Arch, de Medecine Exp6r., 1891, p. 68. 27 Abbott : Bulletin of the Johns Hopkins Hospital, October-No- vember, 1891. 2s Roux and Yersin : Annales de I'lnst. Past., 1889, p. 273. 29 Loeffler : Mitth. a. d. Kais. Gesund., Bd. 2, 1884. 3" Prudden : American Journal of the Medical Sciences, April, 1889. 31 Prudden and Northrup : American Journal of the Medical Sciences, June, 1889. 32 Wurz and Bourges : Archives de Medecine Experiment., May i, 1890. 33 Sevestre : Centralbl. f. Bakt., August 29, 1890, p. 301. 34 Tangl : Centralbl. f Bakt., July 8, 1891. 35 Baginsky : Berlin, klin. Wochen. , February 29, 1892. 38 Martin: Annales de I'lnst. Pasteur, May, 1892. COLUMBIA UNIVERSITY LIBRARIES 1 This book is due on the date indicated below, or at the expiration of a definite period after the date of borrowing, as provided by the rules of the Library or by special arrange- ment with the Librarian in charge. DATE BORROWED DATE DUE DATE BORROWED DATE DUE C28(|I4|)m100 P22 RC138 Parker