REPORT OF THE ! : DIRECTOR OF THE HOSPITAL. OF THE ROCKEFELIER INSTITUTE FOR MEDICAL BESEARCH, January 1916. PHY : Rari? Rene NNT eee ALR Aap ARERRNRERS rendered this impossible. Several men are now under consideration, and it is -pad to begin adritting these patients very soon. ACUTE LOBAR PNEUNONIA: During the past quarter the work on pneumonia has rreceeded largely along the lines indicated in our previous report. The nutor of cases for study has been mest satisfactory. From October first Jamnary first 41 cases of pneumonia were admittod. This is to be compared with . 0 cS cases aimitted during a similar period last year. Unfortunately for the progress >! our main study only seven of the patients have been of Type I. All of these have teen trated with serum. One of those cases died, but this was a case admitted only sc. the 5th day, and treatment could be very inefficiently carried out. Death oc- curred on the 6th day. A striking fact has been that 8 of the cases have been due to pneumococci of Type III, pneumococcus micosus, a much larger proportion of cases jue to this type than we have previously seen. 13 cases were due to Type IT and 11 cases wore due to Type IV pneumococcus. The fact that so many of the cases were due to pneumococcd of Types II and III explains our high mortality thie year, and suggested that the great severity of the pneumonia now occurring in the city at large may be due to the increased frequency of cases due to this type of pneumococed, One of our cases vas due to a gram negative bacillus. This organism resembled somewhat Friedlander's vacdllus but had no capsules and did not grow in a typical manner on agar We have previously had other cases due to a similar organism and it seems that this bacterium is a etiologic agent in pneumonia not previously described. The studies concerning the epidemiology of pneumonia have been continued by Dr Ernest Stillman. He is studying the flora of the mouth in a series of persons vithout pneumonia, using the persons coming to the dispensary for this purpose, and is also studyingtthe mouth flora of the members of the families of patients, and also cf tne nurses caring for pneumonia patients. It is planned to continue this study | aqhcbae Re arm . ~— Z dicta Reg — 3 Wray HT 2 EA wos \- ~Ti.g tee rear. Tuco results so far sontirm those previously obtained. In the mouths ot oO * ! i ' wi 4 ay ao oO $s a) ec : S tie preu..csocsl presons aro of Typo IV, except in certain instances ~O.5 th@ tersens clos3ly associated vith pneumonia patéents, in which case pneumococci 7. i.xe. trros mar se present. In three instances(noimal persons} without history of ivact, pneumcecoscuc mucosus has been isolated. Dr Avery has now collected about X strains of this type of pneumococcus, including those fron patients with pneumonia, a3 912 25 those from normal nouths, and he is raking 2 thorough study to detersine, 2 possible, -sesher any conetant differences(cultural or imsunological) exist between 2 Strains fount in diseaso and those precent in health. It is too soon to report i. the results obtnined. ' ur Doshes jis coatinuing his study of anti-blastic immunity. At present he - atteupting to isolate the substances in the serum which aro responsible for the in- - ition of the negerdal protedl;tic ani glycolytic action. D> Chiskering returmed on Decerber first from. California where he had been vreang vith Dy Gay on the treatuent of typhoid fever by intravenous injections of -2n8itised tyrkoid vaccines, The work was aided ’y a grant from this Institute made 148 ausuum. The therapeutic results are interesting and suggestive. One observa~ sa0u made oy Dy Chickering seeus tobe of considerable value, that is that the mumber oi typhoid bacil1s in the blood during the course of the disease is of considerable trognostic importance. Apparently the injection of the vaccine is followed by a de --9ase in the number of bacilli in the blood or they entirely disappear. The work a8 also confirmed the observation of Gay that such injevtions are followed by a wave t: leucocytosis. The injection of vaccines is usually followed by a severe general vuactvion aud certain of their observations suggest that such reactions may in some ture way be of protective value, even when they are non-specific in character. pas Ae ol 2 ff ; ~rX- wei E Tas subject is worthy of further study. Fer the present, Dr Chickering is busily te ng eae bee: sngaged in prvparing a supply of bacterial precipitates, as studiod last year by Gay ond Chickering as it ids planned te treat a series of cases duo to pneumosoeccus ef Type II with this preparation. Dr Chesney has almost completed a study eof tho rato of growth of pncumo- coccd, especially of th: phonemonon which has ben describod as bacterial "lag". In broth cult. s there usually first occurs a poriod in which multiplication is wry slow. Fora tine no militplication whatever may occur, indosd, as Gillespio hos shown whon th numbc inoculated is small there may ba no growth at all. Follow ing this letont period a poriod cf vaximum rato of multiplication occurs and then acain a yricd of decline. Chosey has shown that the occurrence or degree of lat-nt poriod,or lag, depends upon tho stzge of growth of tha culturo from which tho subehiture is mado. If tho forrer be in the stago of maximum or logarythmic a growth, the subculture may show no lag whatever, whoreas if the culture be in the earhy or late stage tho lag may be marked. The curves of the firat fow hours of growth of the sub-culture parallel almost exactly those of the original culture during the same period)h If during tho period of maximal rate of growth, the cul- ture de placed in the ice box and kept at 0°C, the culture coases to grow, but on rericval from the ice box it will again grow at maximum rate(without lag), even if kopt on dice for as long as three days, and subcultures from this same culture kept on ice will also grow at maximo rate, without lag. | Pneumococe’ of Type IV, when freshly isolated fron ths human body, show a very marked lag, nuch greater than pneumococci of Type I or Type II frashly isco~ lated from the human body. The minicum generation time of pneumococci (Types I and IZ) has be sn found to be from 25 to 30 minutes. The idea is entertained that lag is an expression of injury,which view is sor’ ad by the experiments so far performed. Attempts have been made to deter~ WE Sr ee SRN oe 2 ate + tera: sete oo es aay mina whether cultures showing marked lag are less virulent for mice than those not ~%- oe ke ohowang Lar, cat it has not been possible to secure clean-cut results, as yet. “itu. ta Cullen, Dr Chssney hes followed the change in H-ion concentration “hich o¢cur in a calture of pneunccoccus during its grcewth ond the experiments done thus far show «. striking parallelia: betwen tho growth curve and the H-ion con- ccntration curve up to the point where growth coeasos. After this point is reached, tho i-icn cencentration re:ains constant for days, although the pmsumococci dacrease in numder and autélysis occurs as is cvidenced by 2 partial clearing of the culture. Cultures of both Type I end Type II pneumococci attain the sems H-ion concentration, ana growth in cach caso caasas at this particular level of H-ion concentration. It is interesting that at the tim at which this lovel is reachad, the culture of meu- aoececua Type I shows twice as many organisms per unit volum as does the culture of Type II. This would indicate that the metabolic activity as masured by H~ion con contration, is areater in the case of Pnoumococcus Type II than in the case of Pneu- noceoccus Type Ty. Dr Moore has been civen charge of ‘the preparation of irmame serum and is also continuing his study of the action of ethylhydrocuprein. Attempts are be- ing made to produce rapid and effactive immunity in horses by the daily injection of small doses of cultures, as was shown last year could ba done in rabbits. ‘The préparation of the immune serum for experimental and therapeutic purposes has now Srown to be a considerable undertaking. A very large number of clinics, boards of health etc, are now determining types of pneumocecci by the methods devised here and almost daily requests ars received for serum for such diagnostic and experi- mental purposes. We are also supplying serum for a few clinics for therapeutic usése It is impossible at present, however, to do this except in a very limited Serux of Type I and Type II is now being prepared, however, by the New York Way » C.t7 Board of Health, the New York State Board of Health and the Pennsylvania State 7 ee ee . fe ates ast ' -\- djoard of Heabth so that it is hoped that we shall be relieved of the need of com tinuing or extending this work. The New York State Board of Health is making pre= saraczions t¢ determine the type of infecting agent for physicians in the larger cities of tre state. In this vay will undoubtedly ba obtzined observations and statistics of great evideminlosic=~l significance, At prosont o series of coses due to Pneumococcus of Type II and Typo II! <6 veins treated by ontochin(ethylhydroduprein). Lost spring Dr Moore made a ctady of the bactericidal effect of ths blood soruni of rabbits following the adnin- istracvion of optecnin. Curves made by plotting the b-ctericidal power at intervals Pollowing the aduilnistretion of the druc wre ods. Similar studiss were also wis On 2 few acrml persons. This study permitted the development of a technique suich may now be employed in the study of patients. The number of patients treated is still too tow for any conclusion to be drawn as to tho therapeutic effect of the x3, but so dar the results cre promising. In any case, the effect of the drug in. increasing the bactericidal power of the serum can be readily demonstrated and repeated doses have a cumlative effect. We have already had a distressing example of the toxic effect of the drug,khowever. One patient 16 years old, received four doses of the drug 0.5gm. each, over a period of 36 hours. Following this she be- cam? completely blind, and the total loss bf vision lasted six days. She then becane able to distiguish light from darlmess and there has followed a gradual im- provement. It is at present impossible to say whether or not complete recovery will occur. This seems te be one of the most severe cases of amblyopia which has ocourred following the use et this drug. Some cases are now being treated giving very enall doses of the drug every two hours, but administering a total amount of 1.5 gm in 2% hours, as it is not likely that any smaller doses can be of any valus. It is planned later, in a series of cases to cambine the drug with immune serum. Last yeer Lister in South Africa, published a short payer setting forth that when pnewmsecoccd are grovm in dirane sera they become more susceptible to won action of nomml ssr2n as shom by the power of normal serum to cause agglu- tin:tier und clse opsonization. This phenomenon he called piantication(to fatten slaughter). He showed also thet such organisms becore less susceptible to the act: cn of tha izmuane serum. A sories of studies have therefore beon made by Miss “or te investigate this phenomenon, studying pnoumoceccd of various tyres. It has tocr found trae tint when pneumococcus of Type I for instance is grown repeated- ly in serum of Type I it may become Ho a slight extent spontaneously egglutinable vith nerm:l ssrua, but more strixing and of grecter significance is the fact that it boctsws much less actlutinadle with the homologous serum, and alse now becomes readily agglutinable with serum of Tyre II. With this change in agglutinability the pneumococci lose their virulence. If such pneumococci were now observed for the first tine it would be difficult to at once determine the type. Passage through eninals, however, readily brings bacx their virulence and elso makes evident the specific cgglutinedility, which is always of tha some character as thet originally pre sont. The change in the orcanism occurs after five to six passages through oroth containing one tenth part of immune serum. Orzanisms have now been passed thooack as many as 95 transfers in serum broth over 2 period of one year, ‘The chanzed character of the organism may persist for as many as 50 transfers on broth, thcugh, as previously stated, it quickly reverts on animal passage. The inter— pretation of this phenomenon is at present difficult, and studies are heing made vy immunization of animals against these changed types etc., in the endeavour to fing underlying factors. At the presentt time the significance in relation to the question of epidemiclogy and origin of tyres does not seem to be great. In any case it is entirely different from the socalled transformation of organisms as described by Rosenow, oo ee be i ast rE UE NTI EGS IE SO, OEE IT RT! oR Chae BR Sake I ELUTE TI rs re ‘ | Sao 4 i hogan } . : i i j a —~- —-_ i Diabetes: Only children and adults suffering from the most severe type 6: this disease are being admitted for study, These cases are under the immediate core of Dr Stillman. Dr Allen's study of this disease has made two radical inno- wtions in the treatment, first, the valuable effect of prolonged fasting has been onstrated, and second, the important rOle which exercise plays in the treatment wos been shown. Moreover, it has became evident that the treatment of the patients —wr they have becans aglycosuric consist in education « teaching them how to live “itn their restricted functions. This cannot be done by general instructions, but -awh patient(or 4f a child, the parent) mst take a course of instruction in the diet mde which are believed to zive a more suvistactory account of the effect of di-italis on blood pressure than do fisures can r3sed of averaces, The time when the Clinical effect of digitalis becomes evident ia being “ocpared with the time when alteration in the 2 wave occurs. Studies are also bem ing made te decide whether a larcer dose of digitalis given in a short time has the sare effect on the electrocardiocram aS & small dose given over longer periods. The action ef dimitalis in 108 cases of pneumonia in respect to chancea ia the T wave and in conduction time has been atudied. 58 cases that took no disita~ | lis served ag Gontrels. 50 oases took digitalis. Of these only 40 were available ter Study, the others not havine had an anount of dizitalis sufficient to influence the curve. Of the 40 available Cases that took disitalis, 37 were studied. Briefly stated, the observations showed that in the absence of digitalis 90.3 per cent of the 21868 showed no chances in the electrocardio-ran while of those who took the druc, “8 per cent showed chanze of ene sort or another, These figures show that dicitalis | ~ Tiv< “odaces an effect even during the febrile period in pneumonia. As to wrethor the drug is beneficial in pneumonia the observations offer -) ;rccise information, We can, however, draw some deduction fron the following ts: din examining 126 cases(those (108) already mentioned, torether with 18 other -.5S not inoludec in them for certain reasons), 12 cases(9.5%) developed either fib~ ‘lllation er flutter, 9 recovered from the irre ,wlarity; 1 left the hospital with it; 2 died while it was still present. When the irrercularity beczan 4 cases had had .2 di italis; the others bad had very exall doses which could not be rerzarded as the -2.se@ Of tue irregularity. If the irrecularity existed and lasted sufficiently long, | 2italie was able to reduce the heart rate by blocking auricular impulses, just as it -#S under ordinary conditions. In these cases showing these irregularities there~ sore the beneficial action of the drug is very evident. We are continuing the study of the action of digitalis in fever with the view cz ottaining an effect more rapidly than has been possible by the use of the doses rieviously employed, narely 0.4 cram per day by mouth. Digitalis is now being em ployed in doses of 1.0 cram or more by mouth in 12 to 24 hours. Cpystalline strophan~ thin ds also being given, using very suall doses, on account of the unexpected irregue larity in results encountered some time ago. These studies have ‘been begun too rea cantly te give a report of results. | Experiments are being conducted with the purpese of studying hypertrophy of the heart and its influence on the form of the action current of the heart. The nature of hypertrophy is being analyzed by studying the weight of the layers of the heart as obtained by dissections made according to the method of MacCallum and Mall. “hen the layers are separated by this methods they are not coextensive with single caanbers. The methed of study is as follows:~ after X-ray plates and electrocar dicgrams are obtained, hypertrpphy is produced in one group of dogs, which are made to work by running on a tread mill, and also in other groups in which different val~ ~ YK vulnr lesions have been artificially preducei, Xeray pletes and eleotrocardiograms are made reyeatedly durin; ths period ef observation. On the conclusion of each ex- viens, the heart is dissected in the way described and the layers weighed and the Li'LtS tarared with controls. Chezdcal Laboratory: Dr Van Slyke, with the assistance of lir Cullen and lz .kLecn has continued tre wore on tne fate of protein digestion products in the body, ocmocrith Dr Layer. The work with Dr Leyer had snom that amino acids from digested croteins enter the circulation urnchnnged, and “0. it are absorbed by the tissues, each 3: which possesses its own store of free arino acids. It is mown that the greater mat of tus protein nitrozen absorbed is turned into urea and excreted within a few wee > appeared possible,however, that urea formation might not begin util the vicsusa da general have taken up such an aiount of the avsorbed amino acids as they eijaire, the ureaeformine mechaniagn serving to rid the body of the excess. Consequently lo-s after a fortyeeicht nour fast were fed with meat and the blood urea was determined several times yer hour. Ir some experiments X-ray photocraphs were made in order to correlate the nrogress of tne food throush the alimentary canal with the production of avsae It was Zound that urea -ormation does not wait until an excess of amino acids abéve tne requirerer.ts of the orcaniam have been absorbed, but begins the moment ab- sorrtion starts. Increase in bleed urea occurred within mich less than an hour after reading, as soon as the X-ray showed the first passage of food inte the ducdemm, and 23 S000 as any increases in the amino acid nitrogen of the blood could be detected. The urea-Pormming mechanien is, therefore, immediately atimilated into action by the absorp- tion of amine acids, and does not wait until they have accumilated in excess. One other point in protein metabolism attacked has been the question as to “tether not onl¥ aming acids, but also peptones or other intermediate protein products are absorbed from the intestine into the circulation. The blood proteins were pre~ cioitated under conditions which leave intermediate products, not only peptones but ~ tr- vex, aloumesés, in solution. The amino nitrogen was then determined in the filtrates verors hydrolysia(free amine acids) and after hydrolysis(increase = intermediate prom -.0ts,rentones or albumoses). It was found that, althouzh in the sare experiments .rlé increases in fre amino acids of the blood occurred during digestion, no increase 24 all da the intormediate protein products could be measured. Consequently little cr no eoserption of "peptone" as such occurs. All the protein,eo far as determinable