1; Hoa,lt Al B,lblrc' Hanritz P&k@48 1 - 17 la -7 -ad 28 ? o ? "1 . ":, : \ `- . , REPORT OF Ti3E WORK 13 TZE HOSPITAL. Dr. Cole. `a\ During a large part of the past quarter the director end eeveral mezubrrr of the rtaff have bean aww from the hospital, engagsd in amy actiTitle8. While their work during thir period wa8 not carried on rrith- in the walle of the horpital, it neverthsleor w&a dirsoted toward the rolution of problem m Whioh the hospital staff hm been engaged, and therrforp ohould bo cor~idetod a part of the urtual work of the ho@pltal. In npr last report I ~dreu attention to the fact that pnetxaonia due to rtreptooouol r)ru .probrbly brooodng preralent in the ammo. Thh view w&a bared on the following oboonatioar. Among 7G ouea o? pna\rmonis in soldiers treated in thir horpltal up to the middle of January, 4 were dw to streptooocd. In Deoember Dr. I?oohor WIU o ?? by the Swgaon General to Camp Bowie, and hir obrarvationr them lndlastod thrt.a con- siderable ntznber of the cams of pnrumnla occurring there were not oaaea of. typioal lobar pa-La, but mro ea8& of broncho-pneumnia srsocisted with the preranao of knolytia otrdptocoooi. `Two autopsies whibh had been parform& hero on the rtreptococcur cma8 and the obrervationr of Doahes mnd Jobling at` Camp BOUTLO indicated that the pathologica+ anatomy of the rtraptoooemm CXMOI differed eerenfiallp from that of true lobar , pnsnBlonia* It sekned of great importance to lurra more eoncern$ng the nature of thir acute pulmonary infection. Thir was ompeoially :lmportault for US in riew of the fast that oon6lderabls difflcrrltp. was being encountered in certain of the caaxpm 1~ determining the tspo oP"@mum- OOOOUR responrible for a considerable numbefr of the cmeo, and alro that, owing to thir diffiotity, a sstiofactory oeleczlon of c38ma -2- /' @ suitable for rs-uxn treatIoent wag not being uade, Coneequently the matter was presentad to Col. Burrs11 aad Col. Lbngcopo of the Surzoon General' 8 off ice and it wae decided that h grot;(p of men ehoull be sent by the Surgeon General to one of the q c-r for the pwcose of studying thi 8 problam. In order to carry on thlr work ratirfaa- torily the civlliane in the protlp chosen were given temporary conmir~ionr a8 contract surgronr. This coumirrlon Included Dr. Cole, Dr. Avery aad Captain Dochez from tklr hospital. In addition there wet0 Dr. YbbOallum md Uout. van Glahm from the John. Hopkino Xorpital, who were especlolly detaIlad to rtudy the patholqlcd anatonpl, Lleut. Blake formerly of thlr hospital, Captain IUnrolls and Liautr. RIvera, John and Stevenr. It .uae decided to carry on the study at the Base Hoopitol, Fort Sam Houeton, Ban Antonio, Texas. `In the prosecution of thir work the dirsotbr was absent from his regular hospital duties from Sanuary thd 28th to Idarch th4 25th. I The prellmlnar;r survey of the came in the base hoepl tal mad8 it evident that all the oases were not of the sac variety and that OUT present knowledge ,dld not petit a ready differentiation of tha caaeb of the different kbde.. ,An extensive etatirtical otudy was the'refore out of the ?uerti.on' *L$` t)ieTe'fore a very careful clinical, bacteriological end patho- lo&al rtudy of -a limited number of caseo was~~rtaken. The follouiag ' is a pop of txs qnOiG8i0n8 from & report to tikict ,`, . Surgeon Generali. DiSdUSSION AT?% C'Ol?CLUSIOQ nTh6 studies .iniicate that the oamea` of pneumonia at the Bare Hos'pitsl, Fort Sam Houston, are chiefly Of two v8dtle8: fl?8t, Crcute lo& pneumonia, which doe& not differ eerentislly from that which occurm elsewhere; and. eeconri, broacho-pneumonia, which In most caees, at pre8OXlt 1 at least, follow8 me88108. The PUb'OW~ l~8iOn8 in ZlIOSt c8808 Of this type Of broncho- pnmmonia are charaaterlrtia md specifia and have been studied and de-' raribrd by Ik. IkXalltmr. The etlologlo. agent in all the case8 studied by US h8U been 8tr~tOCO~CUS hnrmra~tiaU8. There Ir n0 evidence pre8ented by this WOrk that indi08te8 that pn@WCOC~ ~USOS the lO8iO~8 and aOllmptOm8 of th18 condition. Rmumonlr following mba#leS may be due to pneunococu~, but the puhnnrry leDIOn la then of the lobar variety. This corsrpllcatlon Of XWlShIS, howaver, 18 UO~W8tiVOly rW.0. ~808 miy occur in which both types of inf8ctIon and both types of le8lon8 are present. me requenor of events in rash &Babe 18 difficult to dsterminr pd 18 probably not always 02 the w. 6 0 Streptoaoccur lnfectionr follorrlng Jobar pneumonia occur with - oon8fderablo frO4UBncy in this hospital. * Broacho-pneumonia rimll8r to that followlng ~marlsr mey also probably occur as & 80~~1 of acute lob& pnetmsnla, though the evldenw for this 18 not coiclu8Ivo. Whothor In the case8 of o trept0c0ccu* empyama, mupllcating lobar pnmmnla, pulmonary leDiOn due to th0 StrOptOCOoCi are &Way8 prOHut Or XlOt, h88 uOt been detmninsd. Thei mortality in `the oa8es 6f broneho-pnewmnia is very high; that of unaorqpliaatrd lobrr pnstnnonis ir low. Praotimlly all the fatal . cams of broacho-pneumonia are complicated W o ~yem~. The incidence of myems among the tmcompliuatbb eares~of lobar pneuwnla doeo not seem to I bo axtremsly high. The bumbet of measles cases infoatsd with hae!mlytiC rtrcpto- COOCI m adndrrion to the hospital i8 mt large. The &sJority of the patients with m4aShJS acguire this organism duriz@ their stay in the hospital. The chance of developing yort-maslso o trUptOCOOCus infOCtion8 io therefor@ increased by rerldenoe In this hospital. A, very large number of tae patients la this hospital mff ep 1% from acute lobar pneumonia have haemolytic streptococci In their throat 8. We have no dlnat evidence that they acquire these bacteria in the horpital, but the pn8xxuptIvo evidence indicates that m8ny of them do 80. The work. indicates that the high Incidence of pneumonia in this hompltal, and the resulting high portiallty, has been due, to some estent at least, to info&Ion occurring wIthIn the hoopltal itself. !Fhe condi tionm are not ualih thorn marrounding pumpral fever and surgical wound infec- tionr. Uhllr in meaI108, raw 8urfauo8 do not exist on whl& infection can i 1 OOCof, this dlwsse rOILder8 the reapIr8tOry mucous membrane especial~ rplnerablo to Infection with streptocoocl. PO88ib~ in other di8tBt%8f38, a8 scarlet fever and even lobar pneumonia, similar COndltiOn8 exist. When infection 18 onae rtsrted in a ward In which the putients are ~1088~ ar8oclatsd, the streptococci kcoms widely dlstrlbated; they probably gain in vilplencs with ropoated Wanrfer through the human subJect, and seriour and wide-mpread Infection results. Robably the conditiona la this hODpIta are not unIqts~. ft is possible that the wide-mprwi lncldeno of fatal pneumonia In the Other + ' army hoapltalr pay have a rikl1a.r explanation.w @on our ret\rra from Texar we lmrned that a eonslderablo number :of soldlsrr &faring from &ate pulnwnary rtreptoooccw inisotion were alro be& admitted to the Eospltal of the Rockefeller InrtitDto. Mart of there coma@ givi no hia;tory of previoor mearlmr ikectlo~~ A Coruldwablo msaber of them maffer from enpyem. It bar bsen imposisibh to learn as yet whether or not there case8 are identical rrith tho80 seen at San Antnnlo. In 8ny C&&SO OBfpyO~ 18 i mO8t 8erioU8 co@i~tion and the further study of thlr condition la meet important. About 1% ctituree of haemolytio 1) treptococci, the mo'c~pce of eech one of rrhich in know% WOPO brought bat& with w from San Antonio. Dr. Dochsr md Dr. Avery arr now engaged in a oomplete rtudy of the cultural and especially of the.imPrmologfcsl properties of thee0 strakm. It is abv~ously of very great importance to lawn whether all bhe organ- lama obtained from there CIOOB of pneumnia and empyema are ldenticrl and rrpeo1all.y whather th@ are identical with the heanolytic o trsgto- cocol whioh wo have irolatod from normal throatr. During pqy ahrmoo the ho6pita.l faullltiee have been largely devoted to the arr of patienta ruffrring from pnemrrmis, soldier@, ralorr gDd civiliuu, and to the lnrtmution of m medical offloerr in the unre and treatment of patienta suffsrlng from thir dlmeaee. Sinoe November flrmt 25 w medical offloerr hnve received or axe now receiving traniag here. The 1-g. armmt of olinicf%l merterial has tie it porrlbls for them man to reoolve an axtenrive e~srieace. Sines October firrt of thie par 235 pa$lentr mffering from pnstxaania hnr been treated; 100 of them were roldierr, 28 aailore, and 107 civiliana. Our reeordr ehow thst of therm oaee@ 186 were frank lobar pnmaonIa, and of there 66 were due to Type I pzmkcocoi, 32 Type II, 26 atypio+ Type II, 13 Type III, and 49 Type IV. Of the reminder of the O~L)I 41' ham been oonridored to be due to rtreptoooooi. Thir figure, howover, ppry not be abro1utel.J correct ow5ag to diffioulth8 in diagnorir. Thlrf) five of the patient8 have suffered from empyema. In 10 inrtanesr cultures from the smpycrma fluid showed the prerenCs of pleuaococol. In 26 oase8 etreptococcl were prorent. Of the88 28 aa8e8 12 have already died. Thirty-tm of the cmea of bmpyema were operated won; of there 10 have died and 22 are rtill living. The high mortality in the empya CBS~B evsn under condition8 80 ratirfaetory a8 there iza our om &r Demonrtratlon Eospital afford further evidence of the great need for further study of thir condition at the present time. Antipneu&oooio Vsccinst ion. In qy lar t report I 8 trted that prrllminary work on thir 8UbJeot wao being mdertaken and that Captain Austin had been detailed to tha hoopltal to work on thir problem. The work ban been oontinued during ~qy abrmoe and lta prmtlonl appllcrtlon,ln a conrlderable au&or of roldirrr ha8 been made at Camp Upton. All the vacoino haa been prepared here snd the work ha8 been uarriad on Jointly by Captain Auntin working hers end MaJor Cool1 st Cw Wpton. The following report h68 been preparod by Captain A-tin. nTho following report oovor8 the propxratlon mnd adminimtxmtlon of aatipnaunococoio vacolne and the o taby of the effect8 of the vaccination on the sera of a few of the vaccinated ~a888 and the 0 tstlotloal data qmn the inoidence of pnrtarmnia wrong the maobated end unvac+mted troop, up to March 24. . PREPARATION: The metlia &opted we8 0.5 per oent glueore broth, one liter of which inotiated 12 to 14 hour8 givsr the 8&u jrielb u 10 liter8 of plain broth or as 100 Bl8ke bottler of glueore agm. Organlrnm grown In gluuocrs broth give a8 good agglutlnin production in r&bit@ u tho8e grown in plati:brofh 8nd better than those grown on agar. Centri- fuging was done at flrrrt on the two large bucket centrifuger, taking 2 and 5 liter charge8 rerpootively. R\;m 0ontinlaoufIly `from 9:30 A.m. td 5 p.m. ( there would centrifuge about 18 liters. A Sharp108 oentrifugrl wmtrif$2~ latsr i.nrtalled in the laboratory, which centrifuged 15 liters in 90 UdnutOS and could be prepared for a repetition of thla yield in a half hour. Ihim made the haadllng of 25 liters of broth daily, the capacity of the media mom, rrrlly poralblr. The vaccine haa been auepended la ssft solution mnd has received a double heating at 55 degteae for a half hour, once before centrifu&g end again titerwards. Stwulardization bar been done by dilution and cou@arlron of the opacity with easled tuhaa of knom m~psnslonm, controlling this method uith freqmnt Wrisht counts. Trloreaol was add8d md the vaccine was bottled in 20 cc. bottler. One doae was aontrlned in each 0.5 co. . AlRdIKISTRATION: Prellmlnary o xperlxmta on nine membera of the Hoapltal rtaff were made, each receiving a flrat dose o ubmtansously of 8 bllllona each of types I, If and IfI. Severe general reactions fol- lowed in three cares and moderate to 8evere local reactlonr in aeven ~3aea. The dorsge for use in the Cemp was accordingly reduced, 1 Efllion of each Qpe I, II and III being given at the first lnoculstlon and 2 btlllona of o och typo at each of three StiB8qWnt laomilatloa8 at weekly ir)temalr. Ths total dora$s was thersforo 7 billions of each of the three typea. All InJeotlonr were tie 8ubcutaneou8ly. - The vaccine was distributed by &aor Cecil to the Regimental Infirmarl~r arxi the lnJeotiOn8 and recOrd8 wore mde by the regimental surgeons mder; hla dire ctlon. KtZSULT9 : The oora of 13 aa888 were studied before inoculatiOrL None ahomd any agglutinlns. Only one ahowed any protection bgalnrt 9!fps I). The aerli of 33 cauea were atudled 8'dayr after the i&St laocula- tlon. 16 ahowed agglutinlno agcrlnet Tppe I 8ad 14 against `pgps II. In 7 carets the agglutination occurred in a dilution of 1:lO; in the other c~aen at lower dllutlonr. Protection teata were made on 28 of the 30 ama a.- , !1. Mioa were protected agedmt 0.001 cc. of culture (WC!0 lethal doser) of Typ I in 16 aa and agalnrt l/10 this doee in 21 ca8e8. Nice were proteatsd egainet 0.001 cc. of culture Type II in 15 aa808 and agalnrt l/10 thlr dose in 24 c(ues. No agglutinine again@ t Type III were Ob8OXTWd. Miae were protected againat O.aOOl cc. of culture of Type III in 6 C1LIO8. Eight of there 30 O-08 received about l$ timer the standard dare; two racelred $ the etendaxd dorm. The increamod dooe lnarwed the mount of qglutinine definitely but h@ very little effeot on the protective power. Nine CMM received the total rtandard dare in o ring10 injeotlon; four rscelted the total standard do80 dlridad into 7 daily inJeotion8. No olear differmoo botwean the rerpon8a In there groups oould be detect& STATISTICAL RESULTS: Average 8trength of Dlwlrlon Feb. 4 to Mar. 24, the period of the inoculation, Nuribsr of troop8 vaccinated againlt pnoumonla, Ntaiber of `8evere looal reactions, rmny with sterile ab8Ueb8@8, Number of revere geX'Mr8l reaction8 (quarter8 or horpitti) Nuuber of case8 of peunonia ocuurring among unvaccinated troops, Feb. 4 to Mar. 24, Etiology determined, 63. of T@a I, II or III, 14. Nuhbsr of uama of pkmuonis occurring among vaccinated , troops, Feb. 4 to Mar. 24, Etiology of all determined, of Type I, II or III, 1. (A Type I cam ocaurrizig within 36 hour8 of the flrrt inomlstion). 30,ooo. 12,670. 194. 25. 83. 17. c -9. b' !' Record8 of vaccinatsd troops have been made end complete recordr of Cal68 of pneumonia occurring in the Division are being uadb. Arrangement 0 have been nade with the Divieion Surgeon for the continued typing and recording of all case8 of pneumonia occurrlny in the Dlvi8ion during it8 foreign service and the necsrsruy diagno8tlc sera have been provided for thlr pwposa. The o everlb local rsactlonr, occurring In &bout one came in 65, wnountlng in t~omb CB~BII to aterile abacele formation, occur apparently in certain anrasptible individual.8 and there lndivldUl8 raact severely to each lqloutloa. `phry my davelbp a 8evere local reaction to the firrt Injection, an abac.88 after the second (or vice Vera) or thay may de- velop an ablCe88 after each inJection. `ha nbsce8ser davelop crlowly, beglnnlng to fluctuate about the revun:: &'y after inoculation. !l?~ey have not incnpacitsted the men nor kept them from duty. C~tl.ll-38 from the abrwroe~ have alwuoay, been sterile. Re have found that theea asma men develop a marked rsactlon to the lntrcideznal iqjection of a dllutr pneumotoxln prepared by dirrolving pneunococci In bile. !l'hle reaction ~cay serve ar a meant of plcklng out euch Individuals befors vaccination. It ~111 be of irrpostance to study the serum df 8uCh Individuals before Inoculation and CL0 determine whether they are imn&~e. It ie al8o poreibl0 that thlr te8t mey pormlt the inotitutlon of 8ome modified method of in- oc+ation,. by which the abrceeo fOMtiOn may be avoided. Studier are in progrerr COnCOming the relative mesit Q< antigen8 prepared from broth and from rolid madia, heated and killed with- out heating, and inJected In oalt solution or in oil. " `Dr Cohn' The latter # of J&w~uary Dr Cohn entered the army and he been engaged an the organiz8tlon of the cardio-vamcul@r Work- HBrly in March he left for duty in Fn~ree. Dr. van Slyke. I. A clinical rtudy of the action omilltlcr of the dw "A-189", eyntheelzed by Dr. Jacob@, wau begun on Jan-r-y 3 by Dr. StIllman. Recently Dr. Stadie hka entered the hoey,ital from the Presbyterian Hospital and taken part in the work. The Initial doaago and mode of admlnlotration were based on the animal erpertintr of DIP. Brown and Pearce, and planned In consultation with them. The effect of the drug on the heart during and between inJectIona was controlled by Dr. Cohn with tha o lectrocardlagram, the result. being conairtontly negative. The offset hn the kldneyr was oontmlled by urea, chloride, and $hetnolmalphonphthaleln excretion teeto, ae unll an by albumin and micr~rcopio teatm, llkewlee with negative reeultr. No evidence of organic Injury could be obtained at any stage of the treatment. At flrrt the attoqt wao 40 to InJact intravenously the drug diesolved in 3 timer the amount of oodium hydrate required to neutralize Its phenollc hydroryl groupr and dissolve It. The reclson for 80 dolv, :vae that the results of Brown and PetLrce hrzci ahown excees of alkali to decroaee the toxlalty of the drug In rabbltr and increare Its therapeutic effect, without Injury to the velnr. In patlentr, however, the &lkall cauoed thromboels 80 frequently that tha exce~e~ was redused until at present only 1 mo~eculr lnrtoad of 3 10 pled to dirrolrs the drug. Under there conditions there lr no vein'inJ%uy, md the therapeutic effect moema to be mintained. The mb- etunce birsolvad In 1 molecaile of alksLli can be iajaated In a conaentration 0.f 1 to. 250 without vein inJury or dther apparent harm. ) Ikifavorable reaotioq on the part of the patients during or after Injection appqwe to be mpch 1~1s than in the cage of Sslvarran. In two out of thirteen cama the flrrt injeation warn followed by a temperatwo of 101' to 102' and &ht discomfort, Subsequent injection8 did not elicit thlr reaction even In these pstlente. In the othere there wae no dlrcomfort either during the Injection8 or the 24 hour@ following them. When, however, doees were crowded very aloeely, two or thxoa of 0.5 gram each within a week, o evere abdominal cramp8 rerulted In most patienta, The aramp8 bega 1 to 3 day8 after the lart inJection and lamtrd at interval8 for 2 or 3 daya. There wae no evidence of Injury to heart or kidney function, or of other organic irrjury either during or after the attackr, and they left the patientr without any dstectlble reeldual damage. With dose8 dlatrlbuted at weekly lctervalr there has been no reaurrence of the wt tacks. A8 the remit of the flrqt three monthr' sxperlenc8 we believe that we have overaome the dlfflaulties in the nay of a fairly eatlafactory adminis- tration of the drug. The mbrtence is dlsrolved in 1 molecule of Y/Z rodltm hydroxide, and diluted with 350 prrtr of 0.9 per cent rodlum chloride. !Fhe rolution thuo obtained lr injeoted lntravanoualy by gravity. The flrot dole lr 6 mg. per kilo. body weight. !Fhree bay8 later, and thereafter at weekly Intervals, dore8 of 10 mg. per kilo. are given. No other drag ha8 been given until negative Uasoemann reactiona have been oonei8tentQ obtalmd. There- after mercnrio intmotiona anil iodide therapy are instituted preparatory to di rch&rging the pat lent. Thirteen cama have been admitted to the hospital rincm BeaultQ. J-3 - 11 ooldierr and 2 olviliaar. Twelve of theee ca8eo are rtlll u&r observation, Om of the civilfanr refared further tre+wnt titqr,4 .: injections and wan .diachcsrged from the hospital at hir own rii&ot. (a) Clinical manifastatlsgl have been cleared q in a raoet rstir- factory manner. (Chancres , cutawous rasher, xrmo~tl patche a and condylomata. ) -3- (b) tielOn# COntiitlning treponemta have been stsrlllzed after 2 to 3 injsctlon8. (a) Waaeerrnwm reactionq. Of th.e 9 patients who have been under treatment for more than two mOnth8, 7 have changed from + + +r + to negative WaSoerapaOnr. One, a ~1~111an, refused further treatnumt after four doses. Ths rmining ptiont hi!&8 ahanged faW8 + + + + t0 +, -0 excrstagg. The arsenic of the drug ia excreted partly In the urine, partly in the feces. me drug is retained in the body for a aon- riderable time, as ercretlon continuer for three weeks or more after dosage i8 atopped. During this period the retained drug appears to continue to exert its therapeutla action, for'at least two Wassermann reaction0 were observed to clear up two or three weeks after injections had been tsnlpor8Xily euqmnded because of the cramps reported above. lkperimmtr on rabbits Indicate that the final ellmlnatlon of thr arsenic from the body Is complete. Rabbits were heav1l.y lajeated, and kept SOmb week@ until arsenic no longer was excreted in the urine. They were then killed and the different organs analyzed for arsenic. No more WELLI found thsn the tracer Observed in no-1 controls. Apparently dl8appenrance of arsenic from the urine indicates that the drug hai entirely left the body. 2. With Dr. Falmnr wOrk wae reported last yea? on a method for the estimation of total orfzaic a&&&3 urine. The process at &hat time involved a combination of gravimetrl'c and volmtric methods, and was rather laborious. We now find that it can be greatly simplified. By shaking vith an ~~~088 Of calci~ hydrate ~bOWh38 anb'phosphatee are precipitated. !Fhe filtrate Is neutraliaed to phenolphthaleln, and is then titrated with acid using methyl orange as indicator until a maximum color change Is attained, which occurs when the hydrogen ion concentration reaches that of a t1louuetndth-normal H Cl solution. At this point organic acids are practically all set free, but mineral acids, aside from carbonic and phosphoric, to ohly a slight extent. Consqwritly the titration following treatment zith calcium hydrate gfver an approximate and extremely slmgle eetimtion of the or.gcJlic acids. In diabetic urines tested the orgsnlc acid excretion in ketonuria exceeded the normal excretion by amounts correepondlng closely to tha sum of the hydroxybutyric and diacetic acids present. 3. Dr. Goto, a voluntary asslstant,is sngagsd in a study of the location of the reserves of mlner~l aUrali which are drawn won in acidosis. Rabbits were given doser of N/SEClY b:rstomsch tube daily In such amounts that death occurred after 2 to 4 weeks. The soft tissues md dcslatono are being analyzed separately for phosphates, sodim potassium, and caloium. It Is hoped that the results nil1 indicate the relative extent to which the skeleton and soft tissws contribute their mineral constitwnte to neutralize unusual amounts of acid Introduced into the organism. The urines are trlso being subjactsd to mLnera1 4. b. GOtO bib8 study of renal diabeteq on lmaly8es. also, rrith Dr. Allen's . himself. Be regularly advice, made an interesting ercretes small amOunt Of 8ugu after taking meals with ordinary smauits of is not accqprpanied by hyperglycemia, however, and of sugar-burning power. carbohydrate. there appeara The exorstion to be no lorr 5. Dr. Goto's work required a msthod for estimating caPbo=teo ~FOW ent aa aalcium carbona& in bones, and a method ~a8 consequently devised which i,s apparently wrier in speed and simplicity to the conventional mthods nOW used for determining carbonates In mineral anatiser. The proceso depends, . like the blood bicarbonate method previously reported, on the rapidity with :vhich carbon dioxide is removed from water solution in a vacuum. In this case, the solid carbonate is weighed into a test tube, and the latter la suspended . in ir euztion fl~ak &lch contains an excess of N/lQ barium bydroxid8 solution. The flak is evaeuated, and dilute hydrochloric acid Is run onto the carbonat in the test tube. The CO2 eacases immediately, and is completely absorbed in about 3 minutes by the barium hydroxide. After f llt8cing off the precipi- tat.8 of barium carbonate, the excess of hydroriie titrated with N/10 acid. 6. Dr. Dernb;e, a voluntary assiat;;Lnt htzs studied wlth Dr. Arm the of fe& of the reaction of culture media on the urowth of pneumococch. The latter were found to be sensitive to relatively slight changes In hydrogen ion concsntration. The growth tone for all t,vea lies between neutrality (pH - 7) and an alkalinity (pH = 8) about equal to that of blood serum from which CO3 has been allowed to escape by exposurs to air. Outside of this . narrow zone no growth occurs. Within it growth is most rapid at pH -7.8. 7. Dr. Der&v ha8 also studied the autolstic ermmes Of the tiesues. He find8 that each of th8 tlssws 8tudi8d (liver, upleen, pancreas, stom+ch . mucosa) contains both trypsin and pepsin, althou& in the pancreas trypsin ii so abundant that special methods are, reidred to detect the pepsin, while con- ditions are reversed in the stoma& mueo)a. The Optimum conditions for 8elf- digsrtion of tiesues appear to be those under whiah both enxymes Oan act, the popein a~complishlng the fire$ stepr bf digestion, the trypsin completing the hydroIgsie `to the. stage of amino acida. Theee conditions are met by a hydrcgan ion concentrat$on' of 10 -6.6 , which permits both enzymes to act, although it is not the optimum for either. The conditions are alao met by first suspending the tissues in acid solution, In which the pepsin acts, then trHnsferrin& them to alkaline solution, where the trypsin becomes active. Dr. Allml. The clinical monograph ie now complete a,~ far as the writing 18 concerned. while I think it auf fers from the defects which I pre- dicted, it will be found to contain groups of clinical ex>erirPentr which I huve been able to carry out, concerning the influence of metabolic variationr represented by ererolre and more erpeclally by changee In the fat and total osloritte of the diet. The barlc principle of limiting the total diet and metabollcun in the treatment of diabetee ie believed to be adequately sstablirhed by these o aerimente. The permanency of the rarrultr effected by this method bar alro received a tart, 10 far as!tho principle of tI%i3tmeAt has been followed. I am convinced that certain came6 of diabetes nil1 progrerr downward in rpite of any dietetic treatment. Theee rpparently are not more than a mm11 minority, a8 far as preeent evl- dence indicates. Vs bare IL rsries of patient8 In rarioue rtegea of diabetsr, rho have been under observation for from 0x10 to four years now, without alter- . ation in tolenmce except B,I oan be rooounted for by diet. At one sxtrsars are youthful patients taken in the early and more hopeful stage of their diabeter, such aa Natalie Colby, who bar shown no decline In tolmmoe, and Stuart Bradley, who apparently is progrerding toward feoove~`Y. There patient8 appear normal and lead k0rmm.l. livee, with care only in diet, though they are of the type who fomerly died regularly within a few months. At thp other extrane are the examplee of dlabetem oi maximal rererity, suoh aa Stepha O'Brien and Uieo Martin, who are hopeless invalida, unable to 11~0 outs+.do thir hospital. The Important `feature of euoh oaeee is that even theee patimtr apparently eontinue to live through months and pear@, unable to @in tolemmce, but yet not in any ray perceptibly progreseing domward. The obserq , >`i' vatione would indicate that' `in the majority of cam, the etfo%%ic basir of diabetes is not an inherently progressive process. The great majority of Our NO PrOPortiOn Of deaths haV0 been due either to disobedience of patients or a riletaken plan of treatment. . It has been impossible to pursue the clinical study intelligently without an accmpanying pathological study. This has Included both anlmale and patiente, and a pr8lkcimr)' sketch of the reeulte io includsd as one chaptar of the monogmph. There ie reaoon to believe that the basis of dia- betes is invariably pancreatitiq, probably very often of acute chaacter. This hold8 out the hope of preventing downward progress if injury from diet is svoidod. The ncrturo of the injury from diet is conclusively eetabliehed by both animal experiments and obrsrvstions of human speclmans. The func- tional overload results in a oharaoteristic form of degeneration of the ielandra of tungerhanr, which doee not ocour when the diet is kept within tha true toler- moe. In addition to the elrteneive animal work, I have already examined several bndred human speolmens, and there Is a little more work In this direc- tion to be done before complete publication. It is hard to make B detailed report of the chemical studies now approaching oompletion, except by reference to previous outlinea. The con- ception of diabetes as a disorder of total metabolism rather than of carbo- )@rate combustion alone, which is the undqrlying baeie of this treatment, presents a broader problem and require8 more extensive experimental support than has apparently been appreoiated in this inrtitute, and the work involved . `ir not likely to become clear $0 others than the participants until the fin- ished material can be turned in for publication. The following lines, which I sketched in Staff Yesting a year ago, are included in this work: First: me defect of carbohydrate metabolim i8 dietiaguiehed from the rimple loss of eugar occurring with such conditiona as phloridzin poison- a* Second: The defect of protein metaboliem necerekily appears in the form of the carbohyirats and fatty end-products, but a few wggeetiva obear- vationr conaerning -ino aoide hnvs been made. Third: Since carbohydrate and protein were sltcady restricted in diabetic diet,, the chief investigation h&e been dazusnded bJ th3 fat metabo- llm. Thir hae been in two branchee, the first indicating that diabetic scidoelr lo a rpscific, fault of fat metabolian and not due mere17 to lore of uumr, the recond shoring the rpecifio nature of diabetia lipemia. There studier will give the treabent a o ???*???o? inrtaad ?? o n anpirioal barie. Thsy ciin earl17 be finlrhed by thir mummer, but I am not cure that the long reriea of papere giving the reeultr will then be complete. This pub1 ica tion map encroaoh by a few months upon the coming year. As the research, BO far a6 I have guided it, ham been a unit, its completion mark. a good stopping point; and In view of the militav situation, I shall acquiesce in bringing the entire investigation to a close.