a Rm een ah 4 REPORT OF THE DIRFCTOR OF THE HOSPITAL OF THE ROCKEFELLER INSTITUTE FOR NEDICAL RESEARCH April, 1916. April, 1916. To the Board of Scientific Directors of the Rockefeller Institute. Gentlemen: - Tne Director of the Hospital has the honor to submit the following sugzestions in regard to future development of the hospital, and report of scientific work carried on during the past quarter. NEED FOR INCREASED LABORATORY SPACE : Since its organization, the activities of the hospital have gradually increased, both as regards the number of patients studied and the amount of work carried on by the physi- cians in the laboratories of the hospital. This increase in activity has rade manifest certain limitations in the facilities of the hospital and has inade evident that, for further increase, or even for the most aiven- tageous continuation of the work at its present extent, certain changes are advisable. The most evident requirement which has appeared during the past year has been the need for extension of the space devoted to laboratories, The work carried on in the chemical laboratories has in- creased very materially and as a result, the space originally devoted to this work has been mich overcrowded, four and five persons working in a space originally intended for two or three. The bacteriological laborator- ies have also been much overcrowded. It has been impossible to provide Dr. Allen with proper lsboratory space for carrying on his work on diabetes, and he has had to use several single rooms, widely separated. The Director is of the opinion that in order that those who are engaged in making clinical studies and caring for patients may also carry on expeérinental researches relating to the jiseases being investigated, it is very important that the laboratories in which these men work shall be in as close proximity to the wards as possible. He drew attention to this matter in his first outline of the proposed organization of the hospital, and his subsequent experience has confirmed this view. Moreover, owing to the advisable limitation in the mumber of patients, it is important that t:.ese patients be studied from different standpoints, that is, that fre- quently chenical, bacteriological, or biological and physiological studies be carried out simultaneously on the sane patients. To make this possible it is important that the men working along different lines work in harmony and in cooperation. If the laboratories are widely separated, this is in- possible. For this reason it is better that the men work in somewhat crowl- ed quarters than that they carry on their work in separate buildings, or in laboratories widely separated one from another. It is to be hoped, however, that it may be possible to make some extensions in the space provided for the chemical and bacteriological laboratories. To do this, I have suggested that certain of the rooms now used for bacteriology be equipped for use as an addition to the chemical laboratory, and that temporary changes be made on the west end of the sixth floor to provide for some of the bacteriological work. It is suggested that the changes made on the sixth floor involve as slight structural changes as possible, so that if later it is decided to use this floor for patients, it can be restored to its present condition with comparatively little expense. Sketches of the changes proposed will be presented at the meeting of the Board. It is expected that Dr. Allen's werk for the first part of next year, at least, will consist mainly in experimental work on dogs, and it is there- FOr ta e r a fore sugzasted that suitable arrangements be made for him on the second floor ef the present laboratory building, which will be made vacant by the removal of the chsnical laboratory to the new building. It is hoped, also, that on this flecr an oferating room can be provided for Dr. Cohn and also one for other workers in the hospital, whose work ney require opsrative procedures on dogs. ADDITIONAL ROOM FOR PATIENTS : The growth of the work on cancer will probably increase Slightly the mumber of patients cared for in the hospital. It is hoped that next year it will be possible to care for this Slight increase by moderate crowding of the space now available on the ord, 4th and 5th floors, and also possibly by using the isolation building for convalescent patients, when necessary. It is in.portant, however, that at this time the Board consider possible nethods for future increase of tha number of beds available. The Past experience suggests that the need will best be met by providing addi- tional single rooms. In a mixed service as we have, consisting of both men and women, it has been found difficult to separate patients suffering fron. various diseases without overcrowding certain wards and leaving other wards containing comparatively few patients. Such seperation in certain cases seas very important. For instance, certain experiences we have had have indicated that it is very important not to treat Pneumonia patients in ths wards containing patients with heart disease. It has not been wise to Place diatetic patients, who ars not acutely il1, and whose mental state is of considerable importance, in wards containing acutely sick pneumonia patients. It has also been found advisable to keep patients on whom very accurate chemical or metabolic studies are being made in single rooms. Moreover, the demand on the part of persons of the better classes for ad- mission to the hospital has grown, and it is found that in many ways these are the best patients for study, as they are more ready to cooperate in the studies being nade. These patients also require separate rooms. It would seem, then, that the first extension of the hospital facil- ities should proviie for aiditional single rooms. This can probably best be jonas ty using the seconi floor, now occupied by nurses, for this purpose. In ths original planning and construction of the hospital this floor was built with this possibility in mind, and this floor could be used for this Purpose with compsrativaly slight change. NURSES HOME : Such a use of this floor would, of cours3, necessitate nakins provision fcr the nurses alsewhsre. The marses quarters are already overcrowiei. In very accurate work ani complex studies, such as are méde in the hospital, the numbsr of nurses requirei is large, mich larger than nay be thought necessary by those who have only had experience in the ordinary general hospital. The mrses are neaied, not only in caring for the immediate neais of the patients, but they are employed very largely in assisting in naking observations and in assisting in tha technical pro- cedures «arried out. It seems, therefore, that sooner or later a nurses home should be provided. When this is done, provision should probably be made in this building for providing quarters for the doctors, as wall. Vhen this is ions, the second floor should ba available for patients. REORGANIZATION OF THE X-RAY LABORATORY : It has been well recogsized by all those familiar with the work in the hospital that tho X-ray work has not bean carried out in a manner commensurate with the other work done, The squigpment ard service have not been even so good as that of i the average general hospital. It is hoped that provision can now be nade for greatly improving this service. The work on cancer which it is pro- Fosed to do makes such a development very important. Moreover, it is hoped to make certain studies concerning the changes in the size and shape of the heart that will give information as to output of theoretical and practical importance. To provide space it is proposed to enclose the open space on the eighth floor, snd to use all the space on this floor not occupied by the operating suite. Plans of the proposed changes will be presented. Addi- tional equipment will ba required, the estimated cost of which will also bo presented. It is also hoped that one man can be obtained who will give all his tima to this work. With tha excaption of this man, the changes in tha hospital arrangements which will be suggested involve very little change in thea size of the staff. The chanzes will make such future increase possibls, but are not for the purpose of providing for any immediate changes. They will relieve the prosent crowding, and provide proper facilities for carrying on the work as at prossnt planned. Report of the Scientific Tork carried on during the Past Quarter. ACUTE TLOBAR PNEUMONIA :; During the present winter (up to April let) 70 cases of acute lobar pneumonia have been treated in ths hospital. Nf these, 14 dies, a mortality rate of 20%, which is a distinct lowering of total mortality in a very bad pneumonia year. The cases dua to pheumococcus “zype I were treated with serum, unless they were very slightly ill or were admittai very late in the disease, when serum treatment did not seem indicated. Of the cases due to type II pneumococci, a few were treated with the extract of serum precipitate. Many of the other cases were treated with optochkin, Our purpose is to treat cases of type II with a combination : cf optechin and serum, or optochin and extract of serum precipitate. It has oeen inportant, however, to study first the action of each of these agents alone. The following table zives a sumary of the cases and the results as regards nortality. Cases of Acute Lobar Pneumonia 1915-16 to April lst. Treated Cases. Untreated Cases Tyre No.Cases Mortal- % No. Vortal- No. Mortal- ity ity ity I 22 1 4.5 17 serum 1 5 0 IT 23 5 21.7 8 oReesce” 8 9 3 3 optochin+ 0 extract III 12 6 50, 6 optochin 3 6 3 Iv 13 _2 15.4 ' 2 optochin 0 ll 2 70 14 20 % The danger of drawing conclusions from mortality statistics in pneumonia must constantly be borne in mind, but as they stend the results seem interesting and instructive, The results of serum treatment in the type I cases add further evidence for the value ef the inmune serum in this type of case. Our conclusions as to the value of the serum, however, are based on the study of ‘the cases, rather than on the mortality statistics. The statistics give little infermation as te the value of optochin in the treatment of prieumonia. However, the studies of the cases have given us valuable infornation in regard to the use of the drug. Seventeen cases have been treated with optochin, 9 of type II, 6 of type III, and 2 of type IV. Of these severteen cases, twelve have been very carefully studied. These studies have yielded important results as rezards the size and spacing of the doses. Fron. these stuiies it seens that careful attention should be given tc the size of the body in deciding the size of dose required. It is now troight that at least .024 gm. per Kg. per 24 hours should be given. In the aurlier studies it was thought that in certain cases the drug was not con pletely abscrbed, but it seems now that these apparent jiifferences have been due to insufficient and improper dosage. It is epparently best to give a gcod sizei jose at tha beginning and to follow this by snall doses fre- quently rapeated. These results have been obtainei by naking studies of the bactvricidal power of the blood very frequently during the period of admin- istration. By this biological test tha amount of optochin in the blood at any given tins may b> estimated. "ith the axcaption of tha casa of am- blyopia which was observed earlier in the ysar, no further bad effects of the drug have been seen. In the case mentioned, recovery was complete. It is too seen to spesk of clinical results in the cases treated with optochin, but th: inpressions obtained hava been vary decidedly favorable. The clinical results obtainei, together with the experimentel evidence, make it important that the study of this drug be contimed further. It is hoped that ty combining the drug with serum much better results cen ba obtained in cases of type II ani type III than with either serum or optochin alone. Stugies have been mais by Dr. Moora conesrning the scquirement by bacteria of " fastness " to optochin. This is undoubtedly an important question in relation to treatmont. Th: vary interssting observation has bean made that whan pneumococci are grown in serum to which optochin has been added, either ty administration during life or addition in vitro, the pneumococci acquire very large capsules, much larger than those seer when the bacteria are grown in serun alone. By repeated transfers in optocnin-containing nedium, the bacteria are able to grow in very much higher concentrstion of the drug than was originally the csse. After only a few trensfers slight powers of resistance become evident, but several weeks or months zre reguired before the changes beccne of extreme grade. It is of interest tust when the organisms become very resistant to optochin, they zlso becore bile insoluble. Tie supply of optochin in this country is very limited, but per- nission has now been obtained fron. the Germen goverment for a sm.a1] amount te be export2d and also from the mnglish government to allow it to caus throu;h, so it is hoped that we shall now soon have enough for our purposes. Dr. Chickerinz is contiming his study of dissolved precipitate. In his work with Dr. Gay last summer observations were made which suggested that such precipitates acted not only by supplying immune bodies, but also stimulated leucocytosis and caused mobilization of tha normal antibodies. The present studiss ars being made tc determine whether or not the pneu- ‘mococcus precipitates thave any such action. The work has not yet progressed far snough to permit conclusions to be drawn. Pnaunococcus micosus - Type III. As previously mentioned, pneu- mococci of this type have been very frequently found in normal mouths. On he other hand, pneumocecci of types I and II are never found in normal mouths except in the case of contacts. Since the pneumonia caused by pneunecoccus micosus is relatively infrequent and is of very great severity, these results with pneumecoccus micosus are very surprising and make aifti~ cult the interpretation which has been placed on the findings of type I and + om mn seeanneege II as relates to epidemiology. It is conceivable, however, that the pneu- mococci of type III found in normal mouths differ in some way from the pneumococci of type III found in disease, To test whether immunological differences could be found, Dr. Avery has collected about 70 strains of this type of organism from normal mouths, and from patients with pneunonia. He has studied with much care, but no erltura. or other differences could be detected. Rabbits were inmunized to various strains and cross reactions with the various strains studied. The results, however, were negative; no differences between the strains could be made out. It will be recalled that in our earlier studies of this organism it was never fossible to obtsin an immune serum which would agglutinate these organisms unless the latter were first treated with acid to remove tha capsules. In our work rabbits, sheep ani goats were used in the attempt to produce an immune serum, but on sccount of the results obtained, horses were never employed. The immune serum from smaller animals had slight protective power for rats, but it had absolutely no effect when tested with mice. The State Board of Health under Dr. Wadsworth's direction, however, proceeded to inminize a horse, and after several months inmunization sent us Some serum for testing. To our great surprise it was found that this serum had well narked aggiutinating power for pneunecoces of type III, and also soms protective power for mice, 0.2.cc. serum protecting against doses as higa as 0.001 cc of culture. The agzlutination reazttion is very short and complete in low Jtlutions, but does not occur in high dilutions. The degres ot protective power 2oes not suggest that the serum can be of much effect in treatment, but the demonstration has been made that 2n inmune serum can be obtained from horses and it is not impossible that methods may be found for increasing its potency. This serum was tested by Dr. Avery against all of the strains which he had collected, and was found to be active against all but 3 cf them. These 3 strains were non-virulent and were from normal nouths. However, it was active against other non-virulent strains from normal mcuths, so that it has net been possible by this serum to distinguish between the parasitic and non-parasitic strains. In general, the strains from normal mouths 2re less virulent for mice than are the strains from cases with pneunonia, but this is not constant. The frequent occurrence of pneumococcus mucosus in normal mouths, therefore, is still obscure. Further studies are being made on this problen. Ths imme serum had no effect on four strains of cocci with large capsules and forming mucous, which, however, were bile insoluble, were haemolytic and did not ferment imlin, end have therefore been called strettoceccus muicosus. The serur, therafore, offers a ready ueans of distinguishing between Pnsunococcus naicosus snd Sterptococcus macosus. Dr. Avery hes also studied the effect of growing pneumococci in dilute solutions of bile. It has been found that by prolonged growth in this medium, gradually increasing the concentration of bile, the becteria become accustomed to concentrations of bile, which with the untreated strains cause immediate solution. This property, however, is lost efter one or two transfers on non-bile containing medium. Epidens.c.ozy. Dr. Ernest Stillman has, during the past winter, made a study of tia types of pneunococci present in the meuths of a large munber cf uvivial parsons, contacts 2nd convalescents. This material, in ary a addition te thtt already ottained by Dr. Pochez and Avery, gives considerable information in regard to epidemiology, though there are still many obscure Guestions. Dr. Stillman has studied 270 specimens of sputun. from 246 normal nouths. In 152, or about 50% of the instences, pneumococci were present. There has been no difference found in the percentage of persons harboring pneunococcus és studied in the different mouths. This study, however, has been entirely carried out during the so-called pneumonia nouths. Cont inua- tion of the study through the summer may show differences. In 2 instances the pneumococci found were of type I, 4 type II, 14 atypical II's (a,b,or x), 23 type III and @3 type IV. In all ceses but one in which type I or II were found, the persons harboring then. vere closely 2zssociated with persons suffering from tha disesse. The epidemiological significance of the carriers of atypical tyre II and of type III is more obscure. It seens thst in this respect the organisms more closely resemble the type IV pneumococci. The extrer.s virulence of the orgsnismsa of type III, however, makes this difficult to understand. In this connection a surprising obser- vaticn has been made. Pnewmococci of type III very quickly diseppear from the mouth end sputum after an attack of pneumonia due to this organism. On the othar hand, they may persist for months and even years in normal mouths. It is hoped and expected that other interesting and valuable informz- tion will ba obtained fron. this statistical data after the work has been complete 2. Production of Innune Serum. The two most important practical points to be solved in the study of immune serum are improvements in the methods of producing serum se as to produce a more active serum end, second, methods of determining proper dosage. A tes eat Considerable work has already been done on the first of these prob- lems. Last year the study of inmunization of rabbits showed that better results could be obtained by the use of small doses of dead organisms, freqcently repeated, than could be obtained by living cultures. This nethod nas now been epplied in two horses, one being immunized to type I >neumoceccus, one to type II. In both cases, after immunization over a period of 6 to 8 weeks by the method mentioned, sera have been obtained which are as zctive both as regards agglutination and protective power as sny serum. we have previously had, using other methods. Attempts ere now baing male to drive the immunity higher in these horses by enploying living cultures, accoriing to the method used by Dr. Flemer and Dr. AILoss. It is hoped that in this way the effectiveness of the serum can be increased, but in any case a mathod for aconomizing time and horses has been secured. Dr. Avery has also conducted some experinents to study the haemo- lytic sction of pneumococci in the hope of using this reaction as a delicate test for immune bodies. The experiments bearing on this problem are not yet far enough advanced to report, but he has brought confimuation of the con- clusions drawn from our previous studies, that the haemolytic action is due to substances contained in the bacterial cells, and set free on their solution. Dr. Chesnay's studies enabled him te test the haemolytic effect eof cultures at various stages of growth. The cultures began to have haenolytic power only at a period when Dr. Chesney was able to show that dissolution of part of the organisms in the culture wes occurring. This haenolytic power persists for four or five days, then gredually dissppears and after eight days is entirely absent. Dr. Chesney has contimed his studies concerning rate of growth of pneumococci. By means of observetions carried out on the supernatant 3 . Pte EES fluids ootained by centrifuging portions of a culture at varying intervals during the period ef maximum rate of growth, it has been demonstrated that toward the eni of the period of rapid growth substances or factors are present which bring about the death of a large proportion of the pneumococci, which substances remain in the supernatant fluid after centrifugalization. It has further been shown that the process of destruction or killing of the yneumococci follows or is identical in its rate with that of a so-called honomolecular reaction of physical-chemistry, and in this respect the effect of the fluid constituents of the medis upon the bacteria is analogous to the effect ( observed by other workers ) of bactericidal agents such as phenol end bichloride of mercury upon anthrax spores and upon cultures of bacillus raratyphosus. Furthermore, some evidence has bean eccumul2ted to show that these bactericidal substances in the culture medium disappear in part when the culture is ellowed to stand in the incubator for severe] days, for e filtrate obtained fram a culture at the end of 24 hours incubation shows decidedly more bactericidal activity for sctively growing pneumococci than a filtrate from the same culture 48 hours old, and at the end of 6 days incu- bation, when there are no longer any living pneurecocci present in the culture, the filtrate frem thet culture shows decidedly less bactericidal action for actively growing pneumococci introduced into it than did either the 24 hour filtrate or the 48 hour filtrate. | It has been possible te cause pnewmocecci to grow less rapidly by exposing them to the action of filtrats or supernatant fluid obtained from 24 hour broth cultures of the same strain, if, after exposure to such an envirorment at ice-bex temperaturss, th pnewuiecccci be renoved and rainocu~ lated inte unused broth. Attempts have been made te fellew the behavior of pneumococci from actively growing cultures (during the period of maximum rate or growth) when injected into rabbits intravenously, and to contrast, under these conditions, the behavior of these actively growing pneunococci with the behavior of pneumococci which would show a definite lag in the test tube. The study is not complete, but the preliminary experiments sugiest that ferhaps there may be a differenee in the behavior of "young" and "old" cultures of the sana strzin of pneunococcus, when they ere injected intreven- ously into rabbits, the individuals from a culture during the period of nheximun rate of growth tending to increase in mmber in the blood stream eof the rzbbit somewhat more rapidly during the period immediztely follow- ing injection than io the individuals from a culture which is no longer growing rapidly. It is proposed to carry out this study at greater length. Dr. Dechez has contimied his studies relating to the enzymotic activity of pneumococci. Ina previous report it was shown that antipneumococcus serum possess the capacity to inhibit the growth of pneu- mococcus in vitro. After this phenomenon had been definitely confirmed, an explanation of its mechanism was sought. In the course of the investi- gation it developed that antipneumococcus serum has the capacity to inhibit more or less completely the peptolytic and glycolytic functions of the Pneumococcus. From this it has been assumed that inhibition of growth is in part at least dependent upon the antienzymotic properties of immune serum. This quality of inhibition of metabolic function is possessed in varying degree by the sera of normal animals and may have some relationship to their natural resistance, Human sera during lobar pneumonia exhibit the capacity of inhibition, and the degree éf inhibition reaches its maximum grade during the period of recovery from the disease. It is thought that for the animal tody te rid itself of infection the growth of the infecting microorganism mist rirss be errested, and that only after this has occurred do the more specific substances have an opportunity to exert their full effect, An attempt has been made by use of the nethods previously described to throw some light upon the phenomenon of parasitism. It is obvious that, in order tor a microorganism to develop a parasitic phase, it must be able to grow in the 2nimal body, which implies the development of a nechanism for resistance to the antigrowth influences of animal sera. A study of the Pneumococcus shows that the metabolic function s of organisms recently isolated from the human body are nore resistant te the inhibiting factors of both normal and inmune sera than are those of organisms which have led & saprophytic existence for considerable periods of time . A study has also been nade of the nature of the antienzynotic sub- stances of the inmune sera. It has been possible to obtain specific inmuns bedies ina fraction of the serum which does not exhibit antienzymotic activ- ity, but no light has been shed, so far, upon the actual nature of the sub- stances themselves, or upon their source. They are thought to be non-specific in character, and their efficiency is helieved to be markedly enhanced by the presence of specific inmune bodies. Up to the present time, work has been carried on entirely with living organisms, a difficult procedure .in work ef this kind because of the low virility on artificial cultivation of Preumecocci recently removed: from a parasitic state. For example, it takes seme weeks for a strain of pneumococeus recently isolated from the human body to acquire a capacity of uniform growth on artificial media. A consid~ erable simplification, hewever, has recently been made in the fact that a pepteciybtic fesmant ass oeen prepared which is active in the absence of the livin; zsll. hit wethod should render the interpretation of compsarstive er res waooveee ny em, wi tosh | SRTOLVAMeATS Wash Wars reujiavie. DIABETES, Dr. Allen : The principal effort is now being directed toward publication of the dats st hand. The work still in progress centers around the acidosis problem. All diabetic patients are now cared for by Dr. Fitz. Practically no patients ere admitted except those with marked acidosis,ani Dr. Fitz is studying especially the concentration of acetone bedies in the blood and urine. There are two current theories of diabetic intoxication; one, that it is a pure acidosis; the other, thst it is a specific poisoning with acetone bodies. Acidosis is being measured by the c2rbon dioxide of the blood and alveolar air, and by the total acidity of the urine. The concentration of acetone bodies is being determined by a nodification of Marriott's micro-rathod. Obviously the typical patient approaching coma shows high acidosis with high concentration of acetone bodies, but in special cases it may perhaps be possible to separate the two factors and learn whether one or both may be chiefly responsible for the entire con-ition or for individual symptoms, or whether there may possibly be another factor, viz., intoxication by yet unknown intermediary products, especially these arising during fat metabolism. As is known, the treatment employed in this hospital aims especially to prevent this intoxication and to remove it when present by means of fasting and suitable diet, rather than to attempt to neutralize it. But in patients bordering on coma, the question of alkali therapy inevitably presents itself, and evidence is accumulating that intelligent use of sodium bicarbonate is beneficial at a certain stage in some cases. The ‘oses used. ere, however, reletively small, and the alkali is exployed as a temporary adjuvant, and not as the principal treatment. It is believed that the reproduction ef human diabetes in experimental animals, and the experimental foundation of the fasting treatment, are now & fairly complete, with the exception of the feature of acidosis. 4 few animals have been caused to develop what appears to be the same fatal intox- icaticn found in human diabetes. Hitherto no satisfactory reproduction of diabetic acidosis in animals has been achieved, and the present study is therefore believed to ba important, to complete the experimentel counter- Fart cf the clinical disease, and also to afford a basis for a more funda- rental study of the condition than is possible in human patients. Five patients of this Hospital have been studied in the Russel Sage Calorimeter, under Dr, Eugene Du Bois and staff. From the sane standpoint, a few diabetics from other hospitals have also been studied by Dr. Da Bois. A paper (Allen & Du Bois) now in Fress embodied the results with sll the Rockefeller Hospital patients except one. The results are essentially as follows: (1) The existence of the Lusk dextrose-nitrogen ratio of 3.65 : 1 in certain cases is confirmei, but this is not necessarily a "fatal" ratio and such patients way recover considerable tolerance. (2) The respiratory quotient under these circumstences is about 0.69, All the severe cases showed very low quotients, indicating that they were actually of greater severity than most cases called "severe" in the literature. (3) The metabol- ist. of severe diabetics is increased when compared on an accurate basis with that of similarly emaciated non-diabetics, or when the same patient with active diabetes is compared with himself when free fron active symptoms. These results sre believed to be important in this disputed field. (4) The metabolism is zreatly reduced by the fasting treatment. One patient showed a fall of 25% in the basal metabolism during the initial fast. The lowest metabolism observed in these patients is 36% belew normal. (5) The respir- atory quetients prove that restoration of the carbohydrate-burning function cccurs under the fasting treatment. (6) Respiratory quotients have been iourd quite Irequertly which are puzzling, because higher than can be eccounted for by kncewn facts. COMICAL LABORATORY, Dr. Van Slyke: “ith Mr. Cullen and Dr. McLean, Crk. on the fate of protein digestion products is being contimed. Up tc the rresent, it has been shown that amino acids increase in the blood during digestion, but that the intermediste compounds, or peptones, do not. The itudy is now bein, extended to discover the eifect of digestion on the wroteins of the blood plasma. | It was found desirable to improve the methods for quantitative istermination of the fibrin, globulins, and albumin in the plasma, and .1, Cullen has succeeded in making these cethods sufficiently accurate and conveinent te permit their use in experimentation on a considereble scale. Thefibrin is precipitated from th: oxalst) plasma by addition of calcium chlerid3 undsr dsfinito contitions, end is dotsrminod by Kjaldahl. The alburins and globulins aro saparated by tha ususl ammonium sulfata nethod. Ths difficulty here was to find 3 s&tisfactory moans of removing tha anmonia in order that ths nitrogen of the protsins might be determined. Boiling with svan dilate alkali decomposes the protains. It was finally found that if magnesium oxide were used as alkali and alcohol added in ascertained pro- portions, the ammonia could bo boiled off completely in 20 mimtas without decomposing the protsins. Miss Vinograd has been engaged in a study of the proteins of human rilk compared with thosa of cows! milk, the distribution of the nitrogen anong the various types of emino acids baing daterminad by methods woriied out previously in out laborztories. The problem was sugzested by Dr. Holt vecause of its interest fron. the pediatrist's standpoint. Tha results indicate that the zlbumins from the two milks ars of definitely different Nee N\, unr, ; wo. . amino acid composition, but no differsnce could be determined in the caseins. Miss Vinograd, cooperating with Dr. Losee ot ths Lyinz-In Hospital, has studi3sd tha distribution batween meternal and placents1 bloods of salvarsar. injectoc into prognent syphilitic women before dslivery. Ths arsenic content of the placentsl blood one snd two hours after the injection was much loss than that of tho natamal, end, in sone cases, was nil. From tic results obtzined, it appears, thorsfore, that ralatively littie cit tha salvarsan pesses tha placanta end reachas tha fosatus. Ths ersenic deterain- ations ware dons by mothods previously ievised by Miss Vinograd for use in Dr. Swift's salvarsan work. Dr. Palnar, in examining urinss of pnsunonia petients, has noted in s3ver3 cases tha prasonce ef ccnsiderzble amounts of sn arpsrently unknown orgsnic acid. Ho is at prasont endsevoring to isolsta 3nd identify this. He is also engaged in perfacting a msthod, preliminary work on which had bean done at ths Babias Hcspiteal, for datermmination of the total organic acids in the urins eftar procipitstion of all the mineral acids, excapt H Cl, by means of barium hydrate, Drs. Stillman and Fitz sre contimaing the study of the blood, alveoler air, and urine in diabetic acidosis. Tha raletionships of other factors to the bicarbonats content of the blood plasma have been studied, with the following results. Patients with B-oxybutyrate in the blood show a lowering of the vicarbonate below normal to almost exectly the extant thst is calculeted or, the assumption that the Beoxybutyric acid displaces its chenical equiva- lent of bicarbonats. This reletionship is temporsrily lest sfter adninis- ‘ration ef soiium bicarbonats, which mey rastore the blicod bicarbonata to wcmmal, snd relieve tha symptoms of acidosis without csusing the disappesr- ance of the B-cxybutyrate fron the biocd. yur. ’ The alveolar carbon dioxide is not so reliabla an indicator of the actual alkaline raservs of ths blecd in diabatics, at least when undergoing fastinz, as it is in normal individuals. A mombar of th? diabstics undor observetion show habitually an alveolar C O 5 tension 25 to 40 points below normal whan tho plasma bicarbonate is normal and there are no synptoms of acidosis. In such patients tho respiratory canter appears to bs abnormally sonsitive. For tha past yoar wa havo been attompting to find a numsrical factor for the acid excretion in the urine which would bear somo definite ralation- ship to tho actual alkaline reserva of th3 blood. The ordinary figures of ammonia excration por day, 2tc., vary so irragulsrly whan comparsd with blocd conditions that tha existenca of any definite relationship betwesn blood and urina seemei doubtful. It now appears, however, that the Anbard formula, hors frankly supirical, does indicate a relationship. Indicating tha deily excration of amonia + titratable acid, in terms of cc. of N/10, by D, the excration par litar by ¢, and tha body weight by W, tha formula oe gives a valus which varies indirectly as the blood bicarbonate, ves, it is nearly zero when the percent of 002 » bound by plasma is at its moxinan. of 80; it is about 25 when the plasna CO, is 55, both figures ex- pressing the extrem2s of normal limits on the border of acidosis; snd it is about 50 when ths plasma cO., also changing by 25, falls to 30 per cant, the point at which acidosis becomes critical. Liks the alveolar CO, , the urinary excretion is only an indirsct maasure of blood conditions, and de- pends upon the normal function of 2n ontire ex¢eretory mechanism, so that urine analysis can not bs so accurat; an index of intsrnal conditions as analysis of the blood itself. But thse ralstionship of acid excretion to intzrn21] alksline reserva appears now so much mora definite that a new Significance end valus can be attached to ths excretion figures. yom A study of the effect of bicarbonate administration on the alksline reserva has yielded results of interest. The bicerbonats is not retzined in ths blood, but arrears te be innediately distributad to 211 the body fluids. Ths ris3 in plasma bicarbonate following sininistration par cs or intraven- cusly is av>roximately tho rise that weuld be expacted as th result of add- ing ths bicarborats to a solution squal in volums to all ths water in ths today, s3tinating tha lattsr at 0.7 of tho body weight. This fzct is oi as- sistance in calculating tha sff ct of a given dos: of bicarbonate. Roughly statod, for an individual of 40 %g. woight vach gram of bicarbonate raisss ths plasma C Os about 1 volums p3resnt. S systematic study of ths thorapoutic uso of biczrbonat: in acidosis is baing taken up by Drs. Stillman and Fitz, and thus far tho clains of Nagnus-Lavy for th. indispansibility cf alkeli thorary in critical acidosis appear to b> substantiatsd. By studying simaltansously ths plasma bicarbonate and acid excration it is hopsd that the use of alksli thorapy may bs put on a more axact basis. Mr. Cullen is coopsrating »ith Dr. Chesn:y in a study of the develop- ment of aciiity during the growth of pnoumococci and the influsnce of the roaction of ths m3dium on growth, NEPHRITIS, Dr. McLsan: Ths study of ths uschenisn: of urca sxcration and urea retention by means cf the mumorical laws governing the rata of excration of urea is beinz continued in pstients with disturbed function due to nephritis, or secondary to disturbel circulgtion in heart failure. In over 1000 observetions made tiiese laws have been found to be valid and to give the maxinum ot infornation regarding the particulsr function of the kidney which has to de with the excretion of urea. It has been possible to follow the changes in-function during recovery from acute nephritis and the downward tendency preceding ursemia. It has been found that the so called tretention" of urea in the blood is, in fact, & compensatory mechanism, in order to provide the condition necessary for its excretion through a damaged outlet. Study of the chlorid metabolism is also being continued in a similar way. This work has presented somes interesting and complicated problems. A sudden fall in the concentration of sodium chlorid in the blood plasma has been observed in patients shortly before death from uraenia, the concentra- tion «f chlorid in the plasma previously being high. This fall has besn shown to be due te an increase in the H ion concentration in the blood, which causss chlorid to increase in the cells ani to diminish in the plasza, as had previously bean shown by Hanburger, both in experiments in vivo and in vitro, We sr3 attompting to oxplain certain fluctuations in the concentration of sodium chlorid in tha plasma, previously described, but not unisrstooi, such as the lowsrai concentration of chlorids in the plasma in pnow.onia, ani in disbetes. Experimental work is being carried out with Dr. Van Slyks te tost ths effect of the introduction of salts, acids, bases and non-vlactrolytss into the circulation on the chlorid content of the plasma , and it has been found, both in men and dogs, thet introduction of certain other salts into the blood by nouth or intravenously ceuses a dimine ution of the chlorid content, water, ure2 and selt is being studied. ENON H “Li eus The influence of dietetic therapy in nephritis, on the vzrious functions of the iidneys, end on edemz, blood pressure, end other symptoms, iS being ctrried cut on the pz:tients under observ.tion. Se fer we have not observed zeny direct rel-tionship between diet, especizlly with regard to its nitrogen content, 2nd the systolic or diastolic blood pressure, ART-DISFASE, Dr. Cohn: Eerly in Februzry, Dr. Jamieson left the hospital to join the Conedian Militery Wediceal Force for service, 2nd since then the work in hetrt disesse hzs been carried on by Dr. Cohn alone. The study of ths action of digitzlis in patients in pursuance of the plan formed some time ago has been continued. The study of the action of digitelis in pstients with pneumoni2 has, in pert, been completed end reported. Tho rasults have shown, first that digitzlis is sctive in pztients with fever. end second, that it mey ba of benefit in certzin c2zses of Fneumoni2. Tha quastion of the best wey to give digitelis in pneumoniz has 2lso rocsived attontion - for two regsons especially. First it is important to be 2bl3 te subjoct pnouronia patients to its influence 2s rapidly 3s possible; second, it has bean suggested thst if the total smount of the prep2r: tion ef known strenzth calculated for = pationt of a given weight be given at oncs, tine will be sevad snd more accurats dos2ge instituted, end simplifi- cztion in eduinistretion accomplished. Ve heve thought it important to test this second point, and heve accordingly treated pneumonia pztients with 2ppropriete doses, given in 2 short period of tims, end in certzin pztients 2ra compering both concentrated end fections1 mothods of 2dministration. We heva errivei et no isfinite conclusion 2s yot, but so far it =ppears thet in studyinz the question of edministration the rete of excretion of the drug, the optimun. concentration in the circulstion (efter 2bsorption), znd the attainment of its threshold value in the heart muscles must be considered. Tz svems thet by a rapid concentrated administrationaf the dryg, the heart muscle may not be exposed a sufficiently long time, =nd the threshold value m2y not be reached before excretion of considereble amounts tekes plsce. The object of single l2rge doses msy thsrefore be defeated. Experiments sra being mzde on the subject of general end special cardisc hypertrophy. The plan of these experiments hes been reported befcre. To produce gensrel hypertrophy we sre running dogs on 2 tread mill two or three hours © dey. The effect on their hearts is being ccntrolled by X-rzys and by the electrocsrdiogram. Ths post mortem findings are to be enzlyzed and cemperei. Spscis] hypertrophy we hope to see result from the expari- mental injury of 2ortic and mitr2l velves. The results of thes3 injuries sro to b3 studiod in tho sem3 wey as those occurring in running dogs. Earlisr oxpariments on stimlus production in the auricles, and on the vigil ind scceloretor control of the sinus ere: have slre2dy been re- portei, Tho anetomice] work is nesring completion and will ba reported later. Certein clinical studies of mors then usual intarast heve been made. First, two instances of vasomotor angina pectorie ( Nothnegsl ) in the case ef young men h:ving marked sortic insufficiency heve basen studied. Both petionts suffer from rapaated daily attacks. In ths caso of both the occurrencs of such deily sttacks is interrupted by the development of febrile sttacks of a few dys duration, accompanied by abdominel pain, In one caso the febrils period occurs with surprising regularity every two woaks, lasts 4 - 5 days, is sccompanied by 2 leucocytosis ( 20000 ) , with & relstive increzse in the polymorphonuclear leucocytes. A cause for the recurring febrile attecks has not been foupd. The tot2l1 cessation of engine] stt-cks during the febrile period is 2lso not explained. Second, a child has been observed during two 2ttacks of scute rheunatic fever with en interval of e year. During the interval the tonsils have been removed. In the first attack a green forming streptococcus was isolated from the blood by Dr. Swift. In the second attack, a similar or-~ ganism has been isolated and hes been given to Dr. Swift for study. He reports that the immunological reections which he was fortunately able to make ( since he hed preserved the original culture and also the serum of enimals immunized to it ) failed to show the identity of the two organiamna, Finally, we were able to observe rapid heart action (ventricular rate 250 - 240 ) in a child of 12 over two long periods, about 8 2nd 36 hours. The rapid sction could be termineted by left oculer pressure only. Tha Pparoxysms of tachycardia were auricular in origin end probsbly depended for their formation on a site st a low level in the auricular muscle. In inter- venin[s periois, the competition for dominance in stimulus production between this site and the usual one can epparently be observed. The heart of this child is enlerged; the valves sre apparently normel, There was no fever, Thers is a history of vague transient cervical glandular involvement. A progressing myocardial lesion seems to be the probable cause of the irregular- ity snd the hypertrophy. CANCER: This wor: is being carried on under tke direction of Dr. Marphy. Dr. Montgomery came te the hospital in the middle cf February to car? for the p:tiants suffering from cencer, 2nd since then threa such 2tionts neve baen tdmitted tri sra being studied. Sevaral more are now irs waiting to racover from operations in cther hospitels before ainissicr. It a8 80 fcr not been necessery to cpen tha specie] werd on the sixth ticor to core for these patients and, as the mmber of patients wit pneunonis will scen bezin to diminish, the present svaileble beds will probabiy be suivicisnt until noxt sutumn. Ths pragsnt purpose of the study is to ascertain whether by small doscs of X-rsy ths same response on the psrt of the lymphocytes csn bs ob-