REPORT OF TW? DIRECTOR CF T?n HOSPITAL PM- OF THE ROCKEFELLER TNSTTTUTE FOR MEDICAL RESEARUH. Tuna 10.1916 c Since tbc last report the work in the hospital has .;tod chiefly in a continuation and completion of work atatad in my last roport to nrogrosa. . PNiWONQ: The study of Dr Stillman in regard to opidomiology, some of the . t s of which woro given in our last report, ie now about ready for publication. In ilon to the question of opidomiology an lnteroeting etudy ha8 rocontly bcon mad0 so-called houac opidomic at Nowburgh, N.Y. which was brought to our attention by tatc Board of Hcolth. Dr Chickcring wont to Nswburgh and obtained culturea f@m . ;in of tho paticnte and contacts. The fatnily con&ted of tho father, mother and childron, one P young baby. Tho mother was takon Ill first and died. FolLowhg four children ware G&on down in accordion. At the tiplo of Dr Chlckorlag~~ deit t,f theec chfldrcn wora @till ill and two wcrc convaloscsnt, Culturae wore mado from A four chlldron, from the t-m sick children, on0 of fathor and 1 rom the woman caring for them. From tho fathor tho convaloscontr and tho nurso, pnmmococci of Typo I cultitiod, The cultures from tho other convalosccnt child mro ncgativa. ThCeO lines scorn vary rignlficant and suggoet rtrozagly the poselbllity of cotlfagion in LUDO~i& The atudp of Drs. Moore md Ch$ckc;ring In regard to optachfn Is aleo a&Wet .,dy ta bc publlehcd. This .lavcstlgat~n has boon important ln d#ormU&ng tho propor 4z.c ia order to cenfcr upon the blood bactoricldal powor, 80 far tho romlfe of tho iJY indicate that bactericidal power of the blood glvcrr a true indication of clinical :cct, `hJWtY-n&no Cascl haw now been studied, and among tho eightson recOitiBg On@ ~8 dose follwod by frequently repeated mall onea only tno have died, and one Of ~0 received a do68 which Is now know to be too mall, taking Into account the patieat*s J might, 1Pho other patient ma fairly wejl treated according to present standard@ . the ergmUm rbtabed rt death prwei to ,be relatively ProPO to be sfffcaoiouB it reomB that it wiu.)r6bbly rf ret ". ff the ?rug doe6 br bearruse of thb soquired r'astnesa; By the present mthod it seems that in all cases tb blood can be m%de bactericidal for pneumococci. A very recent case has been very instructive; The Fatient was an old man and there u&s difficulty in obtaining sputum; Fran the sali= a Type. IV pneumococcus was cultivated. The patient was therefore given optochin and the dosage was correct according to our present conception. The patient, hawwer, died. When the blood cultures were carefully studied, homm-, acd also cultures made directly from the lung at the time of death, it was found that the infecting organism was not a pxmxnococcus but a streptococcus: The stu- dies of the blood showed that it had acquired very prqt bactericidal power for gneumococcua, tit, ae is knovm, optochin has no effect on streptococci. Stubs concerning prmr doss@ of seqm: At VEWIOU~ times during the mme of mr work efforts @ave been made to devise methods which wuuld enable us to determine the proper size and spacing of the doses of serum administered. Here- tofore estimation8 of agglutinative power have not seemed to give mch infomtion, tut lately the matter has been t&en up again and very thorough studies are being mb of the agglutination titm of the blood. The blood is being obtained very frequently both before and after the ad&nistration of senxa. Those samples are all kept and at the end of the disease these samples are all studied under idedi- Cal conditioae and curves are made'of the agglutination titre; In scme cases it 680~~ that there is too long a &lay between the first and seCOnd dose; By stud+ i ing a series of `the treated cases in this way it is believed that the Pmeent methods ofadnbisb=afioncanbe improvedandthe amount of senmusedFo~~Y~ &Iwed One of our last.cases received altogether 876 GO* of se-; The ptient -8 an al- ! i coholic, had ver$ violent delirium, probably delirium tremens. m felt it imd- : Visatie to stop tb semm until ~8 Pete quite sure that the pneumonic process w&S at an end. The patient has had severe serum sickness &t is now quite well and, con- sidering the severity of the disease, it is pro&ble that the serum L@S life saving* IWing the present season we have already had over 100 cases Of pnemonia* UP to the first of &ne from the opening of the hospital 382 cases pf pneumonia have ken treated. I\mOng the cases in which type has been determined, 112 wre of &x3 I. Of these, 70 have been treated with serum, and of these 6 have died, a -- mortality rate of less than 9%. Of the six ho died, two died of complications riot Of pneurnococcal Origin. Thrae :\ere treated late in the disease, only on the day of death, and only one received sex-m treatment in a manner we now consider satisfactory. So far as semm treatxmnt in pneumonia of Type I is conceL1]Dd, therefore, we feel fairly safe in considering that it has a very definite thep apeutio value. Capsular substance: Dr. Dochez ks been mking a study of this 9-s- Con and his report is as follows: Fran the study of the different groups ofpneumococcus ithas beCme apparent that there are differences in the amount of capsular develorolent by the organism3 of the four grape. The virulence &the grmp asmasumdinh~n 'wings is directly proportional to the degree of capsule fomation. Group IV shows Sony irregularity in the capsule formation. Group I has a RelI-defined CaPale; Group II forms a heavy capsule and Group III, in addition to a very vol- uminous capsule, gives rise to a large amount of mcoidmaterial in the e%Uat% which it causes in aniuale. The fact has been noted that Berkfeld filtrates of Pn~OCOcCus vultures V&II& contain no bacterial bodies contain in solution con- siderable amounts of bacterial substance which is precipitable dy specific imame senla bne'wouZi at first think that this specifically precipitable substam.x arises frQn the disintegration or sutolgais of the bacteria themsel~s~ lbi8, hwe=r, csn be shown not to be the case inaszxuch as it is present in considerable amoUntS before measurable bacterial disintegwtia has occurred as detennined by the p~SenC0 Of soluble hemolysin and from the character of the Curve representing the rate of grew+& !Phe substance is present in the early hours of growth tat the and of fW hours in cultures of type In) and is of undoubted bdmial origin base Of its specific pmcipitability, and caamt be entirely due to bacterial autolysis. The amount formed and the rate of formation corresponds e=ctlY to I `...d. _I . . --_ _ .^ l. .I.. ..I. -.._ + 23 %ree 02 Capsular develo~mt of tile different groups; Type III gives rise 3 the largest amount and Type 1 to the least. In cultures of type III there is ;r*sent at the end Of nine hmrs and amount of soluble bacterial substance &ich 12 rwly CWp2rabl8 to tk.0 tota; ,L;z;A1,t of living bGterh in the G= acmt of ;cAlt-a-Q. The greatest gomation of t,he soluble bacterial substance seems to oc- JX duing the period. of active growth of the bacteria The substance can be de- c.o=t=ted in both broth and serum broth culturns and also in the filtered blood of heavily infected animals. From the facts stated it seems unlikely that the soluble bacterial protein present in the early stages of pneumococcus cultures is ti to disintegration of the organisms, but mom probable that it is a produce of pwth. Ths close relationship in amount formed to the degree of capsular dovel- went suggests that tho capsular function is a contixxmue one, and that capsular xtCriLL1 is contimally fomd and thmm off into the medium of envirornrent~ pcmmq - Dr. Allen, Dr. Stillman and Dr. Fitz 1 - Rapid progress is ?Jin,- mie in the preparation of the monograph for publication. The preparation of graphic charts of the cases treated is not far fran completion and th daba Of the anti1 experimmts are also being collected and t&Mated. About a dozen diabetic patients are kept in the hospital, uMc+r car* of Dr. Fitz, In addition to observations of the relation of acetone bodies in bloQd andurine to the clinical condition, Dr. Fitz is now paying SpCid attention to the renal pemeability; findiq marked variations frcm the normal to be frequent in severe diabetes. da0 patient lately ahomd entirely noma1 win% wh~e m@ra acetone bodies and fat OFB'~ m&ably high in the blood, and the alkalinity of th* bloo& vss low. Sodium bicar'oonato caused a sweeping out of both sugar and acetone bodies abundantly in the urine. Animal experiments, which still continue, show that diabetic lipemia and PLebetic acidosis can bo regularly and positively reproduced in dogs, By varying tile conditions, it is possible t2 cause animls to go into cma onmixed diet and alsc animals to go into cog on fEst!ng.. There are also indLcactti.ons that the var- 2' as&d._ _.._"Ll _- 1 ._ _ _._ -._. .._. -. _ . . _ -a rL-'I$ ic xlal pO~~~bilit~ can be repro&ced in &iabetic an&a;ls m&r controll- . I :; .: ondit-1. ms c c;;?$T;l _ In this case the .:;s:; were repeated at frequent intervals, ti blood count on admission V&S . -:~.,OOO, and after a rmmber of treatments rapidly felA to about 18,000. The spleen, :Gsides a slight softening and the disappearance of tenderness and mn, has not been affected perceptibly in size, Treatment with penetrating doses over the spleen is now being employed. CARDIAC Y?ISEIA$E. - Dr. Cohn : Since writing the last report, no add6 tionsl problems have been undertaken. The experiments already reported corzemily; experimental cardiac hypertrophy are being contim& The study dealing with the action of digitalis in pneumonia is about finished and was reported in brief in Washington hefore the Society for mrmnm Ikdicine. It deals with the changes in the g wave and in the 2-g time in the elec- 'rocardiogrsm in pneumonia. A second paper, dealing with the dardiac irre@mi- ;iss in pneumonia is bei:ig prepared; it deals with the $jrequency c9,7$) Of a.uriCUkW rtt,;Ar snd fibrillation, tile :.:.c:-?erlcs and significance 3f khc @CCUr3'e:=lte Of eX" trasystolic irregularities, the occurrence of heart blocJ+ and certain alterations in the 2 wave in the curve, probably due to respiration and probably an e-era- tion of usual alterations. The collection of material for a third paper on digitalis dosage is al- roost conclude& As already reported, the problem is concerned with whether a large dose given in a small period of tirre (calculated on the basis of physiOlOg- ical (cat) units) is a satisfactory method afp *iAistmtion, From our observa- t ions, w believe that under these circumstances the digitalis is probably excIsted in Part, before a sufficient amount can be absorbed by the heart mscle. The necessarily slow anatcmical studies of hearts obtained in eqmriments and of others obtained fran human autopsies are being continued. The latter in- clude cases of txlndle branch lesions, heart block) suricular fibrillation, and one ofparwennl tachycardla. NEF%WIS, Dr.&Lean : the study 0f the 11~3~hdif3r.n ofurea r&antion in nephIdti6 iS bf3hg COAthWd. IA one patient the blood urea content has been varied frcrn .200 to 2.500 grams per liter by changes in the nitrogen inth, with- cut My symptoms, and without any significant change in the mode of excretion, the rate of excretion being parallel with the increased concentration in the blood, Athqta to influence blo& pressurn in cases of hypertensio% by varying the diet, have so far yielded negative results. Thb Study Of chlorid e%retion aAd the IIBchaAiSDJ Of its I%tplatiOA i6 biw contioarsd fn one patient with nephritic o&r~, not due to heart failure, Sat f6mmg produced edbme aAd Salt mt&AtiOA ~thc#llt any change iA the relatioa of the PI- chloridie to the rate of excretion. ft seems probable that salt retantion and edma are rarely or never ate to a primary inability of tb6 kidneys to excrete salt, but t0 SOlIN Mum which red&6 in t&e~ ret8Atian of Salt by the tiSSUeS* CHDlICALWORATO~-Dr.VesrSlyIce: For the most pe~rt, the problems discussed in the AprU report are being continued along the S~Z[IB lines. The fol- hving advances my, howover, be noted. CUllen and Mcioan are contiipling work on the fate of protein digeltion ro:bJCtS, Utilizing our recently perfected methods for &teId~tion Of @aSma pro- -ins. They have FM yet obtained negative results in looking for effects Of pro- -in digestion on fibrin, albumin, or globulin of the plasma. There is no evi- .cCe of the formation of any of the plasma protein6 direct from absorbed digestion *`OduCts. On the other hand, during the first tw hours of digestion peptides a6 ~1 as amino acid6 do appoar to increase in the circulation, although after six :a Only a&A0 acids CM be detected, It appears, thorefore# that during the .rlier stag08 of digestion it may be possible for scrne of tho intermediate products ; protein digeetion to enter the circulation, although during the later stage6 ..ljr the amino acids do so. The canparison of the proteins of human with those of ccusd milk, bgUn j' the chemical wark of Dr. Vinograd-Villchur, has been broadened by the CoopJmtion *' Dr. Auer and Dr. Avery, who are cctnparing the respective caseins and albumina L iol ogically. Dr. Auer is testing the identity of the cow and human Proteins bY .:.zM of the snaphylactic reaction, Dr. Avery by canplement fix3tioIL For the further study of acidosis, especially in diabetes, We ham heen prfectlng for use in further work a new method for the determination of B-owbutyric &$ IA urine, former analyses being either titxw-consaming or too liable to abjec- the influence to trust for even approximate results in the hands of ordinary &E+ lysts. IA the present method 2 to 10 cc. of urine are boiled for an hour in an Wenmeyer flask under reflex condenser with a solution containing definite cOnCeAo tmtbn8 Of sulfuric aoid, mercuric sulfate, and potassium dichrmfe* * Wbtyrio acid is oxidezed by the dichrcmate to acetone, and 6~~eously the wtone is precipirated as an insoluble mercuric sulfate capour& dich at the end Of the hour*s boiling is filtered and weighed. me mg&tS are accurate, and the i-~~itiatiOns EJO few and air&e that t.ha danger of subjective error appears to be :liminatad,