, !.. . . . `: .a ? . .' i r. ,.`* ._ I . \I. i b. , I : -, ." I .r : , ,. I . . :,: ,.I t ;. ,L ` : ,: . . . m OF Tsn;: DIRECTOR OF THE HOSPITAL OF THE ROCSfEl'ELLER INSTITUTE FOR MEDICAL RE8EARCR, I Dctpbsr 1914. To the Yembers of tha Corporation of The Rockefeller Institute for Yrdlml Reremrchr r36nt lemon : In af report of one year ago 1 stated that a large number of thr mmbora of the horpital etaif had joined the medical oorpe of the army and many of them had been ordered o lrswhrrr. Thir exodus has oon- timed, and more of the rtaf f mmhera have .gone into the rervioq until ncr, Dr. Van Slrke and the `Dlr@tor are the only nembero not in, uniform. The horpital i&u alro reoeired a qutuiaril$tary oharaeter through ita dsrrignation M an +ilirry hoapitrl, and it hrrr now ormmd ~rire for :the Director; aa .j, ~011 & for Dr. Jhn Slykr,,.,$o apply,,for, y&ionm. . . 'fhir haa been' done, :. c.:+ `., and within a very rho+&f& the e&i!! &if ril&:~ooa8irt of anmf offioero. ..`:,Y rho Directo: hoper t&t, for the prrrent at leak, h4 will be permitted b.7 - * ,I the SW&~. tinoral to' Hin at the horpital a@ to confirm Its direction. . . :. , 3 . In' January' br. Co& entere.d the remice and in llarch ua% ordewed to Warm wbre he has been acting ,a8 a consultant in aardio- vikular diaeaees. In May Dr. Chicksring, the Resident Phprician, rau ordered to Camp Jackson to carry on inetruction of medical of ficsr8 in the diagnosie and treatment of pneumonia. Oroupr of offiaero have been ordered thers from time to time, and Dr. Chlakering's work, which ir still in progrerr, ha% been of much value. Hie departure left ue without any rerldsnt phpician who had had any aonsldsrabls experienoe in the work of our horpital, and to meet the emergency Dr. Stadie, rho entered the horpital in January to aasiet in the rtudlsr on ryphilir, ra8 mado sating rerident phyrlclan. In rpltcr of tb extreme depletion of the rtaff, it ha.a been porriolr to continue our aativ- t itier and oare for a oonridsrable number of patienta. Thir haa been rendered pomrible by the army rending to un IL eaall number of offioerr to bo trained in the diagnorir and treatment of pneumonia and dotailing to the horpltal eev- en1 men to aroirt in tti invertigatlon being made of the new drug for the treatment of ryphilir. In May a Board for the Invertigatlon of Rbrpiratory Dirsarer in the Army was appointed by the Searotary of War, and Dr. Co10 WLU made a member of thir Board. Thlr ha8 nea888ltated conridsrable abrsnae ix-em the horpital duo to. frequent trips to Wauhington,and to aa oxtended trip .to ;. 'I '4 aamps in -.tb wart .,.in.Yay ,md June, aad Irtoly o trip to routhem Tampa, `which ,: ,:I; ..j , 5: oooupied ,&bout three rsekr. .`: Thir, with, tha trip to ;Texa# lut ing fro noathr, : `::$; : .+;: of rhiah mention rlll,,beirrdr below, haa made it knorrible for _thr Dlnator `$ . ., .( ;, ,.y;g to giro tho'~mme. ooxitinuou%, personal attention to the horpitil 81 hru boon thm ? ,. Inku~tion for Army Of fioeir in the Inmtitute and Borpital. During the sntiro par eourmm in bacteriology for amy nedioal of 1 icerr have been given in the Institute. The Utruct Ion regard- ing the baaterir oonaornod in pneuaonir haa boon glron by msaberm of the hompitti 3 ' , etaff. During one week Of each month, thie teaching work haa occupied a large part of the time of Dr. Doaher and of Dr. Avery. They tive also bsen usoloted In this aark by Dr. Emoet Stilllean. Before Dr. Chiokeringlr departure for Camp Jackson, he hti ch~ge of the inetmction concerning the typhoid bacillus. On April fltat, a laborhtary couree of lnatruction in meciiccll chemirtry for chemist% in the f3anitary Corps WYB orgr*lireQ DJ f-r. Van Slyke, an-c hao been given in the hospital ohemiaal labomtory. Each month about twenty men have been ordered hare and hirve reo%ived inotructian in the methode of medioal chemirtry. This haa made it neoeretiy to turn over a con- aiderkcle portion of tha labamtory #pure to this work. The work hue bean under the tiediate direction of Dr. Van Slyke with the rrrirtance of Capt. Robinron, rho we ordered here far thir purpore. W autumn, aating upon the authority of the Board of Soientifio Director%, the Director cf the Horpital invited the 8urgeon General of the Army ta aen4 to the horpltal Ia llmlted xnmber of medical offl- aero to twsirt in the treatment of patient8 with pneumonia, in order that the officers could become thoroughly familiar with the methods of treatment ew ployed here". The Surgeon General bar reoponded to thir invitation by aendIng officera to the horpital from ttne to,tdao for~vclriour longthe of residence. , Up to the prerant, 27,*of fioerr have been detailed here. Some have remained .:,. .' . P', for only II) oouple of weet8, moat of tb for period0 of fmm one to three , , , !, ;;T: month@. Them of flcorr have lived in the hoepital and have taken the plaoer. of the horpital internee rho have entered the service. Thir arrangement has ' permitted us to aare for a aonaiderable number of patiento with pneumonia; which oare would otheniro here been impoeelble. On the other hand, it ia bsliaved thslt thie rervics bar; been of very great advantage to the amy. It haa been a source of gratification on vieiting the amy ho@pirale to find that the officer8 trained here, even though this training war only rar7 short and fragmentary, are being relied upon to direct and organiae the care and traat- ment of the patients ruffering from pneumonia. Tho problem of dotemining aocurrrtely the etiologic agent conoerned in Ca8e8 of pneumonia in the army hospital8 has proved a diffi- cult mkttor in rplte of the fact that leqo numborr of man have boon trained in thie work In the bacrtoriological oouraoe being given in the Institute labor- otorles. The chief reason for thir dlffloult~ hs bean that tho trained mon hfcve been rhlftsd about from place to plaoe, and from on8 kind of work to an- sther, and very large nunberm of there mon have been rant ovor8oa8. th0 OAly fon8ible plaa to m&o thir work ratisfaotory 8em8 to bo to train eepooi8lly for thir work romn who can be kept psraanontly in the camp horpital laboratories. With tho authority of the Board of Sciontifio Directon, wo have agreed to train women espscially for thle I)ervice, and arrangermbntr ha~o b8en made to rend hOr8 at OACO tOA UgDOA for euoh tl?aiAiA& For thl8 purpore we shall use the labor- atory proriour;ly occupied by the laboratory for thet rtudy of aardlac pathology and phpiology. -ical Studieq. During the paat you=, tha facilitier of tho hoepitti . , ':.,+ wards hmo boon emp$; al&t `intirely &. the oare of patirntr'rufforirrg;`frb"`i: ,T; . ; :,' .".I _`. ., pneumonia and *oi `iho. &f fering f&i' ;&hilir. .a ,,-:. ,,. .: . I_ 1 A la& n&b;; oi the +&tint. .: tre&ed have been"roldiorm rent in from nearby camps. : Certain diffioultl6r have arisen in the control of not appeared to be aorioua. that those dif ficultios could there 8OldiOr8, though thoso difficultier hare Houovor, it haa been felt by tho army authoritirr " beat be overcome by giving tho hoepital a purely IlO8dAd bX'El]r 8tatU8. Thii ha8 boon done by the army by designating the hoepi- tal U, S. Army Auxiliary Hospital Bo. 1 and by giving Capt. Edgar Stillmna, a C'G- member of our rtaff, the &srignation Co;mmlmding Of ticsr. Capt. StillEaA thon report8 weekly to th8 Chief Surgeon of the Port of Frbarkation the coadi- tiOn of tho 8OldiOr8 being tr8atod and inform8 him of the number of bed8 availsblo for pationtr. A lioutonant to acrt as adjutant ha8 al80 boon dotailod t0 the horpital t0 look after tho r8COtd8 Of the men. thi8 entail8 no added obligation8 OA th8 part of tho horpital and will probably enable u8 to be of o till gto&tOr 8orviOo in the way of oaring for sick eoldioro. IA th0 r8pOrf to the gOi8AtifiC Director8 for the m8otiAg of January lQth, I dr8w att8Ation to the fact that among tho oa8d8 of pneumonia in roldiero troatod in tho hospital, 4 wor8 apparently duo to haomo- lfiio o treptoooooi, all of thorn wer8 areooiatod with empyoma and two of them died. An autopoy ua8 obtained io ono of those Oalel. "The lungr iA thin 0~8 rhowod an lrrogularly di8tributod patohy pn8umoni9 proCo88, tho area8 bear- ing 800 relatqoo to the bronohi, but the ontiro pioture, however, not being a oharaoterirt lo bromho-pnoumonla. In certain place8 ~11 area8 word 8OOA whoro the ontiro lung tirouo failed to 8tsin. In other word8, thoro wa8 bogin- Ai:,g nOOrOri8 Or o b8Oo88 formation.W During the autumn and early winter, pneumonia had bun very prevalent In tho 08mpo, ospodially pneumonia in sorociation with m6arlm which rap prorailing to a very great rxtont. On Docemboi 4th C8pt. &c&t of our rtaff.had bmen ordered to Cmp.Bowie, Fort Worth, Toxar, to asbilt in invortigating the ptiumonia rpidario thorn. Ho war joined thero by Dr. Jobling, .urd fogother thay orrriod ia oertain studier oonoorning the etiology and pathology of the OUOI of pneumonia. 4he7 found a $arge nurabor of oawm of lobar pnoumonir uroaiatod with tho proronco of pnoumococci, but in addition they diroovered a wry .brge numbor of cam8 of bronoho-pneumonia or atypfoal 6 , lobar pneumonia, mmp of them a8eOCiatOd with or following msa8188. Autop8ier were pOrfon& iA 27 ruch C&888, and iA i)2 of thmi 8mpy8m8 was pf808At. k%- toriologiaal oxamtition of 16 of the ompysmu fluid8 ehowed the preeence of a hamolytiu rtreptococour in 13 of thsm. The pathology of tho pulmonary lorions wa8 not orhmmtimly rtudisd. ?h888 ObrorVatioA8 t&k8A iA COMOCtiOA with Our OWA lndiostod that the pneumonia prrttiling in the oempr war not all of the tfpioal lobar pmumonia, but that, a8 I 8tatsd ia lay rsport of January lQth, "two kLad8 of pneumonia axirted; ffmt, typical lobar prmumoaia duo to ~~OUIUOCOOC~ of th4 VWiOU8 typ88, snd o ocond, atypical or bronoho-pnomonia dw to rtrcrptococci and porsibly also to pneumooocci". In thi8 report I outlin8d the probbm8 which domand8d rolut ion. I COAlOqUOAtly brought the matter to tho attontion of Col. Rum011 and Col. Longcopo of tho Surgeon Gtmeri118 Office and requested that ia order to rolro there probl8mr I bo permitted to organiS a group of in- V88tigUtOr8 t0 rtudy tho IPatter iAt8A8iV8ly in 000 0-p. P8ld.88iOXl WM @%llt- od for thir aad Dr. HaaCallum of Ealtkore war por8uadod to join th8 party, rinoo it roemod most important that oaroful pathologio rtudier bo mad8 on the ca8o8 rufforing from the atypioal diroaro. A a80mi8sion wa8 organired oonristiag of Dr. Cole, Dr. Awry and Capt. Doohm `of thir horpltal, Dr. Ma&ll~m dnd Llout. VOD O;ldm bi tha Johna Hop&m Unirsrrity, Lieut. Blake, formerly' of thir horpital, apt. -. Kinoella, and Lieutr. Rirors, John aad Storsnr. IS.& dooided to carry on the rtudy st the Baeo Brpi- tal, Fort Sam Hourton, San Monio, Tsxaa. In tho prooooution of thio work the Director UM aboo& fram hir regular horpital duties from Jumary the 28th to Yaroh tho 25th. Th8 preliminary 8urvoy of the case8 in the baas ho8pi- tti made it evident that all the ea8e8 were not of th8 88rne variety slrd that 7 fk. - ' ,' -73-b L our present knorledge did not permit a ready differentiation of the case8 or the different Linda. An erteneive statistical rtudy was therefore out of the question and therefore a rory aareful clinical, baateriologiaal and pat holag- iaal rtudy of a limited nunbrr of oaaea wae undertaken. The following ie a copy of the conclurionr fran my report to the Surgeon General. ~ircurrions and Conclueions. `The o tudiea indicate tkat the aaoer of pneumonia at the Bare Ebspital, Fort Sam Houmton, are chiefly of tro varieties: firrt, acute lobar pneumonia, whioh do08 not differ esrentlall~ from that which occur8 eloe- where; and Iecond, bronoho-pneumonia, rhioh in moat aa808, st pre8ent at leart, fOllOW8 mOtU108. %O PU~IRO~ 108iOn8 in mO8t oa808 Of thi8 typ8 Of bronaho-pneumonia are oharaaterirtic md rpecifio and have been rtudied and d88flrib8d b7 Dr. UaCallum. The stiologia agent in all the aa8e8 rtudied by PI b&u been Strept'woaau8 hfWBIOlytiCU8. There is no evidence prersntsd by this work that indicate8 that pnemnococcus aau8es the leeions and 8ymptoms of thir aondition. Pneumonia following m8a8lss may be due to pneumocoaai, but the pulmonary leaion ir then of the lobar vtcriety. Thir aompliwtion of meaulee, however, ir emparatively rare. Care8 nay occur in rhiah both type8 of infeotion knd both type8 of leeionr are prownt. The requenoo of event8 in ,. ruoh oue'I ic diffioult to doterdim and'ir'probably nbt alnayo the 188~~ Btroptoooocur lafeationr' folla ing lobar pneumon& . oacur, nith oonridenbl8 f requenoy b thir hotpitd. Bronoho-pneumonia rrimi- lar to that following mea8le8 may alro probably ooaur i8 a reqwl of aaUt8 lobar pneumonia, though the evidino8 for thir ir not coaalueive. Whether in the maea of streptoooccue empyema, aamplioating lobar pneumonia, pulmonety lsrione due to th8 rfreptoaoaoi &re aba~8 prorent or not, ha0 not been deter- mined. "The mortality in the ca8ea of bronaho-pneumonia 18 pneumonia very high; that of uncompliaatsd lobarAis low. Practically all the fstal caeea of broncho-pneumonia are aompliaated by empyena. The inaidenar, of empyema among the unaomplicated ca8ea of lobar pneumonia doe8 not 8eem to be extremely high. "Th8 number of msasle8 ~a806 infsated with haemolytic streptococoi on admirrion to the horpitsl 18 not large. The majority of the patient8 with mearler aaquire thi8 organlaP during their rtay in the hospital. The ah&no8 of devrloping port-mezuler 8trf3ptOCOCOU8 infeatiOn8 i8 thet8for8 inareared by raridenae in thir horpital. "A very large number of the patl8ntr in thir horpital ruffering from mute lobar pneumonia have kbaolytiu 8treptocoaci in their throatr. We have no direct evidenoe that thg aaquire there bacteria in the hoepital, but th8 pr8rumptivr evidbnar indicator that many of them do 80. "The work in&loafer that the high inoid9nae of pnou- mania in thi8 horpital, and the r88ulting high mortality, ha,8 been due, to some extent at lea8t, to infeation oacurring within the hospital it88lf. The boa- ditionr are not unlike those rurrounding puerperal fever and surgical wound infeationr. ahile in me(ulee,,raW rurfaaee do not exirt on which infeation can occur, thir direare re'ndere th8 rerpiratorf muaou8 membrane o rp8aially vuln8ra- ble to infeation with rtroptooo&i. Po8eibly ia~othir dieoaaee, M rcarlet' fever and even lobar pnsdaoka, rlmilar `aonditioma' oxirt. When .infoetlon ir onae rtarted in a ward in whioh the patient8 s`n olooely amaoal.&od, the rtrep- toaoaci beaome widely distributed; they probably &aln in virulenoe with repeated transfer through the hum& rubjeot, and rsriour md widorpread lnfeation mrultr. "Probably the conditions in thir horpital are not unique. It 18 Qor8ibl8 that the Widerpr8rd incidence Of fatal QWWOnii in the other axmy horpitalr may have a rimilar e@anBtion." 1 9 Our etudier in Texae indicated the important part whioh smpyema played in the mortslity from.the etreptococcue pneumonia and ue rtrangly urged upon the officer8 at the Surgeon bnerril'r officr the Importance of further 8tudy of thir complication, espeaially with a visw of devising im- proved method. of treatment. The rerultr of our 8tudy in Texar were rapidly con- firmed by obesrvations in other oru~ps. The nature of this serious malady is now fairly well understood. T'here remain, however, many problem8 awaiting solution tiefore ratirfactory procedure8 for prevention and treatment can be oarriod out. Han7 of t'he8e problem. w8re considered in a conference of bac- teriologi.t8 and clinician8 held at the Department of Animal Pathology of The Rockefell8r Lnrtitute at Prinarton on June firrt. The rtudy of oertain of the question8 demanding early rolution ha. been undertaken by Major Doche., bptain Avery and Lisut. StillmM at this hoapltal, and the results 80 far obtained are deraribed b8low. Very ncontly a new form of pneumonia ha. appeared in th0 8l%f CMP8 and t0 o 1888 o d8nt among tb Civilian QOQubtiOn. but 8pring report8 app8fued in the nssrpapor8 of thb appearana8 in mOpean aoun- trio. of an o pidsmis.,of a&s `r&ir& orp disoass rrsembling inf luenra. This' ,.., dissaso has provailsd 6 `a"ao&dsrablo"e&nt~ In the armies abroad.' The..o&t : oxtent and `ssvsrity of `iI& disease there' oa&ot bo d8tormined irk' the toports` 80 far published. .' In eerta~"loa~itiss' at"least it doourred a8 a serious dir- sane. fhero meems as yst to bo no unanimity of opinion by foreign obrerver. as to the otiology, though cortbin observers have indicated their opinion that it 18 duo to the Influsnra Baoillus of Pfeiffer, and they believe the diseare to be identioal with that oocurring in epidemic fom in 1890-91. The direase ha8 now appeared with great suddenness and maverity in aertain of our anay GMpI* A8 a member of the Board for the Invert igation of Rerpiratory Dieeaser in the Artiy, the Director wee laet week callsd to Camp Deveno, Masacrchu88tt8, for coneultation. In thio aamp within two reeks there have oacurred over 12,030 CasB8, in a conrid8roble number of which pneumonia ua8 prerent and with a larg8 number of deathr, reaching on lome day8 over 80 per day. Judg- ing from a for autopsisr 8een by the writer, it ir evident that we now hay8 to deal with another dirtinct form of pneumonia. Pneuaococc 1 and rtrepto- aocci are prerent in there cIue8, but it 8eeme a8rtain that they are not the primary etiologio agent8 cona8rned in this dir8ase. At the time of my visit influenra bacilli had not been isolated in any considorabl8 number of uases, but Capt. Avery of our 8taff, whom I aal:ed upon to rreirt PLO, ruco8ed8d in domonrtrating the presence of these organinn in a coneidernble proportion of the case8 examined. Patient8 suffering from thir diseare are now being admitted to the Horpltal of The Rookefeller Inrtitute, and from mO8t of them it ha8 been possible to irolate the infhetm bacillur. It is believed to be important thst a coneiderable part of the reeimroer of thir ho8pital for so long ae may be neceeaarp be devoted to a study Of this dissass- Dr.. Avery 18 already busily engaged in attempts to improve the methods for demonstration of influenra bacilli in the rputum of ruch CamI* It is al80 Important that k- munologiaal rtudi88 be at oiao undortakon, and thi8 will be done by Dr. Do&es as soon ae he himelf reooverm iron an attaak of the &ease fraa whioh he is now ruf fering. ! ; I Clinical Studier `of Pneumonia. 6' .,`1 m During the pa8t year, 311 cases of pneumonia have been treated in this hospital. This is by far the largest nuinber of pneu- monia cases treated in this hospital in any one year since its opening. Of the patient8 treat8d 146 were eoldiere end 165 were aivilians. of the QaSB8 undoubtedly due to pneumocoaci, 34 per osnt wars Type I, 32 per oent Type II, 6 per sent Type III, and 28 per aent Type IV. Forty-four cases were due to Streptococcu8 haemol~icu8. Of the 84 cases due to Type I, 8 di8d - a mor- tality of 9.5 per cant. Of the Typs 11 aarsr, 9 dl8d - a mortality of 33 per cent; of the Typ8 iII cases, 4 died - 28 per sent; of the Type IV ca888, 5 ,I ied - 7.6 per aent. As in our previous experienoe, the mortality due to pneumococci of Type I: uas low. Tha total mortality also war low. This was undoubtedly due in part at least to the low mortality of Typ8 1 cases, most of which we- treated with .e1?rm, a. will be mentioned below. Of the 44 caaer duo to Streptoaoacu. haeaiblytiaus, 30 ware complicated with mp~ema. PiftSSn of the Strsptoaoaaus hamolytiaus aaser died - a mortality of 34 per cent. Of ths aases amplicated by ampyema, 28 wers operated upon md 10 died - a mor- tality of 35 per cont. Two of the empysma 0~00 were not operated upon and both died. @su Treatmorif. As statod above, the mortality ia m808 dU0 t0 flp0 I, 9.5 per cent, was vov low as compared with our o xporienoo befors wo be- thi tnatment of sases with sorwn. Two of the fatal aases Wore prti.nt8 ad- mitted very late to ths hospital - too late for serum treatment. If we anit these two Ca808 in whioh serum frsatmsnt could not be aarried out, the rortwl- ity was 7.3 per aunt, which is a most 8atisfactory relultr If seems that thers ~a bs little doubt that the exaellent result8 obtained by the treatment of this type of OMO bar been iargely duo to the propsr admbistration'of untipneuxococc icaem. The results 02 serum treatment in the army, as far as reported, have been quite uniformly oatiofaotory. It muat be stated, hon- ever, that In most camps it has been difficult or impossible to cam-y out the mruza treatment in the manner in which we have advised. In oertain omnpr no attempt has been made to treat only the Type I cases, and all cases, due to whatever type of organic, harg had o onan adminlrtered to them. In a few camps, however, notably at Oa~p Upton and Camp Jaoksoa, very agowrto deter- minations of the type of infooting orgaaia were mado, md the aarum was properly adPinister8d. In both these oampr the mortality in the ouod due to Typs I infeotion was very law. It ir hoped that during the oodaing winter rat- irfautory employment `of the forum art be 40 in a larger number of the omp~. Treatment of Cue@ +Lth tip- &IQ to 8trePtooooous hmmolyticus. The result0 of operative treatment of them case8 will be dirourmd in the repert fmm tb War Dsmonmtntlon EIorpitsl. The dkgnoelr of empyma 881 made early In all oases, rrnd the rurgmon war at once called in conrultation. III meet of the 0~08 operskion ~61 performed within a short time aftrr the diroorery of the purulmt exudate, but in me of the oamw, repeated upiration mu performed k;fW op@mtion. The number of ruoh OMOI, however; ia aa& mf f laiont for w `.Do drbu any oonolurionr u to the rel- atiw value of the tie mrthodr. The martalit~ in tha o&or of qym duo-to rtroptooooour wu Ugh, but not 80 high am tbrt obrerved in, Uoy of the ouopr, During the period when thQ ltwgert number of &oe OUOI oo&urred, the Director wae may, and no rrpsairl study dimoted toward demonrtratlng the advantage of Studies by Dr. Docher and Dr. Avery Concerning StrePtoccmus The probla urigned to ue me tho biologr of thir organirm,.baring partiutalarly in riew the charaater of it% immune reaotioar. Yuoh work has preriourly born devoted to thir problem, but there are et111 a number of qusrtionr to be anmered. A root important quertlon is whether there exirtr unity or dlverrit? among the rtralnr of Streptocooour haemolytiour known to bo pathogenic for human bringa. An rttempt to anewer thlr question haa been made by making uoo of the method@ previourly employed in the rtudy of the biol- ogy of pneumoooooua. A Irrge number of rtrainm of S. hLsr01lfi~u~ ~6x-a obtained from pathological leriom in human bsinge, the majority of rtrrinr bQing f mm pationtr rufforing from bronaho-pneumonia, and o lerrer number from infeatlour proosrtaee in other parts of the body. The organimne were rtudied with regard to the following paintat The general biologioal recrotione which would jurtlfy their being olaeeed aa S. hamolytloue; their riruience for the ordinary laboratory animalr; the production of aativo iamunity In animals to these organimas; the produotion of protsotirr immune o m;, the determination of the identity or divereity of different rtrrino by the prothotiw reaotion in animale; the relationablp of the agglutinatioi reaction to the protective ma& ion. l'ba tultural and f ermentative reaotions of all the o traino o tudled were ruoh M to justify their being included within the group S. haemolyfiiour or S. pyogenes, uhiohever nomenclature 3.8 preferred, All the organisms were rbund, gram positive chain cocci with the oharacterirtio cultur- al ohnracteru of S. bamolytfc~~. All were bile iaroluble, and all` dolyred red blood ~011. both when grown a. superficial colonies on blood agar plates and when a twenty-four hour broth culture was addsd to a five per cent suspen- sion or red cellr. The sugar fsmentatione of al 1 the strains were also tested and in general they corrsaponded to those already described for S. haemol]rtl.cue. Yost strains fermented lactose and 20 par cent of the strains fermented ma- nit. The oapaoitv to ferment these latter sugars, however, did not seem to be related to any other fundamental biological dffference. and could not serve aa a baeir of final claseifioation. II. m for leaoratorv aa&& . The rirulenoe of meet of the drains for white mioe, rats, rabbit8 end guinea plgr war found to be low, usibg pneumococous as a standard of comparlron. The virulence could not be mired to a high point for either rabbit. or guinea pig.. The 0rgmir.m war. somerhat more vlrulbnt for rabbits than for guinea pigr. The viruleqce could be mired to a higher point ior white rat.. Bv repeated passages through a rerie. of white Tat., it wae porsible to raise the virulenoe of a number of t4 rtrains, to a wry high point tar white mice, .o that in a oonsiderabl. nmber of imtan~er a da.e of O.oOOOOOOl co* of an 18 hour broth oulture ~a8 o uffioiont to k'ill t4 anl- ral. in tn.nty-four hourr.,' Thir high ddgmr of riruka ir n80~8~ in' odpr \ to titer .ratirfaotorily t4 $rot*ot&vo vilrro Of idane aera. in o wrhonts to tut oro.a Immunity botrsm diffomnt rtrqins. ' j 1 : types of ulimal weti wed, white doe, white rati and rabbits. The `hper~iati : . with mice and rat. were unatisfaetorv, no active immunity b8iaig.ob`rrmd after repeated inooulation of killed organism. In rabbit., howevar, .uffiCient immunity war obtained after three inoculation. of kiiled organire to enabl8 the animal. to withatad tan times a certain lethal doer of living virulent .treptooooci. IV. The devslortment OX Protective hune aera. In the effort to produce an immune serum which would afford passive protection to r;nimals against S. haemolytbcus, rabbits, sheep, doge and one home were ueed for purposer of immunization. All of these ani- Illals, with the sxasption of the horse, gave good protective sera. The aniuals were ixmunired by injecting first heat-killed and then living cultures intra- renouslv. The intravanous administration of living cultures had to be aban- doned because of the loaallration of the living organiame in joints and other' parts or the body. Ths subcutaneous routs was then substituted for the intra- venous. The imznus eera were oonsidered suffioientlT potent for use when 0.5 cc. given intraperitonsally in white mice afforded protection against 0.001 ac. of a broth culture that killed the animals in dotaer of from 0.000001 CC. to O.OOOOOOOl cc. in twenty-four hours. For the successful performance of the test, the serum must be given intrapsritoneally at least sight hours before the administration of the infecting doss of streptococcus. V. wv of stru of Strsot~cus ~olvtious. Use of the aoove #ora has demonstrated that strains of S. hasmolytiuus ers diverse in their immunologic reactions and do not consti- tute a unit group. Furthermore close immunologio relation8hip can be demonstra- ted betreen oertain rtrains and the svidenw obtained up to ths present points to tha o rirtsn4m of types of hmaolytio o treptocooai jurt as there are tYpea of pneumosooci and rmingoaoccl, At least four such types have boon identified so far. In general there o esms to be a reparation betman What 0rcr7 be OlMsed as the respiratory strains and ths septioaomio drabs, inoludiog in ths latter group &rains f roI rept iaaomia, osllulitis, erysipelas, puerpsral 8epsi8, etc. Wham the point 01 contacrt ir between ths8e two group8 ha8 not JOt b.sn detor- mined. VI. &zslutination reactions. Great difficulty nae experienced at first in the ob- taining of satiafactorp agglutination reactions. lith the very highly active imuune serum which me now po6seee more satlefactorp agglutination reactions are being obtained, especially when the reaction ie carried out at 55' C., and when the dilutions are mode in broth rhiher thm In anlt solution. Ae far aa the work has progrersed, the agglutination resctio- correspond with the proteotivs react ions. &ophrlmt io Vaco hat IQq. A few experiments have been carried out with a visr of studying net&ode of prophTla.ctic vaocination. It was found that nirtures of gelatin and agar OBZI be prepared whloh melt at 40' C. These have been used as a vehicle for the suspsnsion of bacterial vaccines. Such vacainss when in- Jetted suboutaneousl~ in anilcals give a good immunity and also produce a mild loos1 react ion. This method will have to be tried out in human beings in order to judge its' general usefulness. Differentiation of Streptooocci from Human and Bovine Souroes. I. Uith the assistance of Dr. Cullen, Dr. Avery hae investigated the Uniting hydrogen ion concent ration in aultures of Strepto- coccus haemolytious isolated from human and bovine eources. Many inveet igat ore, especially Clark and Lube, have shown clearly and conclusively that the final hydrogen icn ooncentration of a culture is a definite biologioal constant, but that the titratablo acidity is variable, depsndinl; on the buffer action of the salts and protein, as well as on the acid pr0duced.z This fact, not yet uni- versally aecspted by baateriologists, has bean strikingly demonstrated by Ayers, rho finds that aertain cultures may aotually show %egativs acid" upon titration, although the hydrogen ion oonosntration has increased. Approximately 125 strains of S. haenolytiaus from human sourues have been studied and compared with about 50 stralns of this organism of bovine origin isolated from mastitis in oows, from milk and from cheese. The lattsr were authentsc strains, sass of wkioh were obtained frm the Depart- ment of Animal Pathology and others Isolated directly by us. Ths hydrogen ion I concentrations were 811 made by the oolormetria method. A definite and distinct diffsrenos has been found between the bovine and human types of this organimn in the final hydrogen ion ooneentration of cultures grown in dextrose broth. Using methyl rod as an indicator, culturss of bovine origin isolated from milk, ma8tL tie and cheese have oonsi8tently shown a pH of 4.5, while those of human source bar. i pH of 5.1. Cullturer with the more -id rsaction rihibit a dafinito clarsti `: red color, while those with a reaction of 5.0 to 5.2 show only a faint ralmon tint. using thir calorimetric method, 90 to 95 per cent of rll knoWx$ 8train8 have re- acted true to type - th8 other8 forrming an intermediary group in which the "methyl red r8actiona fails in absolute claa8ifioation. By the ~80 of m8dioinal methylsno blue, a fw ther differ- ent iatlon hss been found between the human and bovine rtralns on the one hand and cultures of haemolytic streptococci isolated from cheeee, on the other. The fomer, the more pathogeniu group of human and bovine type@, Jail to grow on agar plates containing a dilution of dye 1:20,000, while the Irttsr,.the more vsgatative cheere varieties, grow luxuriantly. Iiaamolytic otreptocoaci, with the exception of these last named organiame,ars extrsme~y rennitivs to methylone blue, even in dilutions aa high ~8 1:503,000. The porrlble chemotherapeutic significance of thir ob- servation ha8 been considered, but father rtudy ia roquirsd betore any conclu- alone may be drawn. Penistenue in the BUBSI Throat of Eaemolgtic Streptococci derived from ldilk and Cheese. Certain lnv66tigntors hare raised the queetlon a8 to uhetbsr ths 6troptOcocci rerponeible for acuts respiratory dieeare in mrsr uny not bo acquired by eatins c'msae and drinking milk. The studies of Dm. Dochoz md Avery, and others have dsm~8trtbtOd cor~clu81~61y that ?? o t~PtoaOaci found in ???????*?? in man are not id6ntictll with the haamolytio 6tregtococci camnonly found in milk and Ch86ae. The epidemlologicerl canclueia~e concernin& thir f ona of pneumonia, howetsr, bare been based largely on cplt~re made fraa the pbar)pps of healthy Human beings as well ai from the throat of patient8 maffarin@ frm ths dissbso itself. The quaatlon bar arlsm whether there conclusions pray not be vitiated by the parsistenca in the throat, for a limited tina at leaat, of haraaolytic streptococci which ware preesnt in cheeaa or milk which bsd been ingested. To teat thir quostlm Dr. Ernest Stillman has mde titurms from tha throat@ of indiVidIXLl8 a ehort time following the ihgbstion of ppih and ch6660 known to comtain haemolytic 8tr6ptococci of tha bovine typs. @ltums fr& the sa. throats, made before taking tb milk or che@ea,' had been sho*i to be free from haemolytic streptococci. Tim experiments made with milk, which have been frequently mpaated, $I;* shorn that within an hour following the ingestion of the milk, ersa thapgh the latter contained large numbers of streptococci, no haemolytic str+3ptococcu6 colcmies can tm demonstrated cm %he rarface of the p1at.m inoculated by rwabr in tbs ordinary way Tb, rason for this is probably two fold. Fire t, bp natural ~~`0~860~ thy pharynx IS probably vary quickly rendered cleia of any Uril'K particlea, md second, the haemolytic streptococci in milk have a relatively slight power to produce hebemolyais when only ieolatad COlmi86 occur on the eurface of blood a@r. It la not likely, tharrfore, that orrora may arise from t'ha presence of milk streptococci in the human throat. da reg&rdr the cheees etreptococcl, howsxmr, there ie a gnakr poesibi~itp that they my give rice to error in epidem1ologlcal 8tUdleB. Tb grsateet length of time that these streptococi m&y bs found foIlOwing the ingestion of cbe66 haa not yet been d8t6tined, but certainly for several hours. In the firrt place thhese orgrulisme are more actively haemo1ytio, when grown ~1 the surfac6 of blood agw, thm bm ml& rtrains; &nd Secondly, tb throat probably rid8 ltoelf of the particles Of cheese with lees readiners tbtm it doe8 Of the milk. The pO68ibility of error due to this caum should, tbersforo, k kept in mind ln swing carriers, oat it is not likely that any considerable cantision he brisen from thlr 6OurCo in the put. Anti~ococcus Vaccination. In th6 annual report one gsar ago, at tention ua8 called to the posulbillty of amplaying prophylactic racclnatlcn in the pre- vention of pneuQoni& in the Axmy, and it wa8 etated that studies ocncemiog this method were being mada by Dr. Chickeriq. The nfmlt, Of tl*SO StUdi.6, 88 M)u b8 LIupbr0U8 StUd%OS~O by Dr. CdS inth, prO&lCtiOIh Of ixfimity in 6#i;imal6, 86 well as the 6tudl66 carried Out by Dr. &iStOr in Sa;lth Afrioaindicated strongly that pro&lactic vaccination in mm against pUWIl6OCOCCi Of Type6 i, II, and III would be very likely to yield favorable reeul t6. This aarrtter m bronght to the attentlan of Colonel Russell Of tha %wg6on @m?d~s Offica,and captain Austin was ordered to the Hospital to carry on lnve6tigation6 concerning the kchniqua of mfmufactura of vrccino. ?diso Paul1 wa6 employed by the fn6titute to a88flrt in this Wok by the use of a epscial form of centrifuge, it was found poaelLl0 to prepare large amounts of vaccine wi tbout difficulty, and tsets were made on rari ous members of the Staff to detsnntne the moet euitabls dosage, etc. With the cooperation of YaJor Cecil of Cami, Upton, a large mber of soldiers at that cxuq (about 12,000) were then glvon prophylactic inJectlone. The men remclined in tfre camp only for two to three months following tb injectione and wetb then tranoferr!d ' 0YerB.M. hrlng this period, howe-r, not a ca8e of pneumo~la due to the types of pna-tiocsiursd for the inotnalation occurmd among the inoculated man, while a canridsrsble number of such caeo8 oocurmd among the men not inoculated. Attempt8 mm mLd8 to obtain mcordr of the occurrence of pnemonia In there men following their txwmfer to Frame, and a grant of money was gemaraualy mad@ by the Mractora for thlr purpose, but for military raeaono it has boon impo88lble to carry out thir intention. The rem1 t@, ho-wever, have been felt to be 8ufficisitly prolkislng to ju8tffy the employment of thie msthod on a lar*r 8calo. Ths wozk haa been taken over by the Axmy, and the vaccine ir being pmpamd on a large roale at the Army Yedical School. By laaking 8n ed8iasl Of the bcrctsria in Oil in8tead Of in 8tit 8OlUtiOn, it is believ8d that one inoculation will suffice, inetoad of using three iqjsctionr am was fonner1.y done. Large numbem of aoldierr am now being inoculated by Drr.Cecil and Papghan at Camp Jackron, and by Dr. Austin at Camp Dir, bpici Method of Etiologlo Diagpoeir in the8 of Raaiamonla &a to Pnownococci. Ihriqg the p& Dr. Avery has aweloped a rmthod whereby the type8 Of ~wwIOCOCC~ pre8ent In 8pUtUm can be determined within five haarr in many oe.ee8 without autploping mice for this _ntlqose. By in- OCtiathg the rrjut~m in oflb per cent glucowe broth containing five per cant of blood, a rapid growth of goeumococci occurr8, while other organiUPe prwmnt do not multiply to any great extent. After the blood cellr and badaria are remomd by can trifugalizatlon, the type of pmumococcu which has grown uy be determined by the derr,onstratfon of the apeclfic prodpitina in tb mper- nutant fluid. Thir method, while not applicable In all carsr, baa prorad of great value in the campa, eepecitllly when mice we- not arailablr. Use of Maakr in Pnventing Infection in &ring the part winter gauro nrasks have besprr onqloyad in a nur&er of campy for the purpoao of protenting tb tranrformncr, of the bacteria cawing pneumonia frcm the per80118 rufferlng from the di8eaas to heal thy psroons. Tha ume of mark8 io bawd on the wall-known oxporimentr of Pfldgge ccmcarnlng druplot lnfactlon. No careftd exprrimmtr, howevw, have yet been m&o to detormiru the efficiency of the ????? o mplopd in this cam try. Caarequentlp, it was thought advieablo ta have Capt. Wt aad Lieut. Lyon, Amy Officer0 sent be23 for inetruction, invertlgata thle cub- ject. Thdy hAve repeated the erperlments concrrnlng droplet infection, employing masks prepared in different mnyr, and have dsvlred a psrk which ham been rhown by experiment to be efficient. They hava also rhom tbtst amy of the ma&e now being employed are of little or no value. The raaultr : i of this rtu4.y will b mbU&ed iun-iedistely and will undabtedly b8 of' ar;rch ,a : `_ : practical value. .. e'- &ring the year Dr. Goto, a voluntoor aerirtrnt, has, under Dr. Van Slykerr dlractlon, carried on a rtudy cancerairrg tin low tion of the: raemrrslrof minoral alkali which an drawn upon in aoidOrl8~ Ho har aleo mnde an intorooting study of renal d.iabetaa, and haa alro dwirad a method for dete&lning carbonatr in mineral analyrmr. 2, hmbY of Smdeq a voluntary a66i8tmt, haa rtudled with Dr. Avery the effect of the reaction of culture media ou the growth of pn*umococci. Under Dr. Van Slyke'o direction be has IdsO rtud1.d the autolytic enzgmOr Of th0 ti6SUe6. Dlabotm. Dr. Allen haa completed hl s studies In the Hoe~ltal concerning alabe toe, and the cllnicsl mport of hie work ir now in procear of publication by the Ilmtltute ar a Monograph. Dr. Allen hao entered the radical ~emico of tha Amy and ha8 ken o arigned to the hoepital at Usxood tb unciertake ths care of roldlers o uffaring from dlabe tam. . " Clinical StudieqJoncuthe Uee of A 169 in the Treatment m- .' y I -hilie. , In the fall of 1917, plane were made to teat olini- oally in the hospital the areenical preparation, A 165, which, out of a oon- riderable number synthetlaed by Dr. Jacob8 and tested on animala by Dro. Brown and Pearce, had been aeleoted ae the noat promiring for the cure of hums syph- ilir. After reveral conferences between members of the etsff of the horpital and the laboratories, it wae agreed that the hoopital undertake the problem of working out the clinical application of the drug. The responribility and OxFen#O of this work war to be borne by the hospital, with the exception of th8 preparation bnd rtandardlaatlon of the drug. Q&&&l Plq-gf lnv~ . The original plan of investigation was to take patlentr with Ntlve, primary and reconclary leliono, ae well aa porltioe `IImremumr,, in ardor that the effeot of the drug on both the lerioa and the blood reaction might be aecsrtalned. The pationtr wore to br chooen from thore who had hrd A0 previous treatment, Aa the drug, if rubcerrful, promised to have great mll- itarp kportanoe, arrangement8 were made with the officials at the Port of hbar- kation, whereby eoldierr ruffering from ryphilir uere tranrferred to thir hoopitrl (LI pdisAt0, where Dr. Stillman, and later Dr. Stadie, aooepted oor~aiarionm in the Medical Department of tha Army. The work was begun in Jaawy 1918 by Drr. Stillman, Van SlyLo and Cohn. It war plannod that Dr. Stillman should o tudy the therapeutic effect on the Vaeaormann reaction and the effect of the drug on active mifertstion; that Dr. Van Slyke ehould rtudy the mode in which the drug ~&%a ox- creted and retained: and that Dr. Cohn should control the eleotrographio behavior of the heart during and after administration. On the Xfret of arch, Dr. V. C. Stadie from the Free- byterian Hoepital war added to the staf I, and hae divided the alinioal work with Dr. ~tilltran and cooperated with Dr. Van Slyke on the problezr. of nrsanic excretion and dirtribution in the tieeuos. During the preeent month, Colons1 Rueesll has detailed to uo two additional men, Dr. F'ortuine, formerly of the Preebyterian Hospital, and Dr. Klauder, who had been for a considerable tim treating o yphilltic patient8 at Camp Upton. Occasionally Dr. Fordyce haa sxminad the patient6 and has asrirted with advice. Drs. Brown and Pearce have been regularly consul- ted in connection with the plans made for adminirtration of the drug. Suggsr- tionr which they have made, ba8ed on ths`ir animal experiments, have been utilized. The following pointr have been investigated. They have sot bean taken up chronologically in the order in which they tire given her8, as several points uere, during moat of the tirm, simultaneously under in- vartigatlon. 1. bt what dowmurt tm be niven to produce thmmeutio rerultti It wna found that the injection of dorage of 7 mg. of drug per kilo body weight once a reek roaulted in the dirappearanoe of the external leeionr within an a&age period of 9 day., and a negative larrwmann on an average number of 47 day-r. 6oma patien$ta oleared up much more rapidly than otherr, while some rb- quired extenaire treatment. Xn no oase, exoept there in which treatment was rtopped for reasons other than failure to tolerate the drug, did we fail to firullf obtain li,nsgrative W8rrermsnn reaction, Ae the roldierr who were patient8 oould not bo kept from th8ir military dutim for an iad8finitr period, the W?P- tiv8 Ka888rmaan ruaetion, when obtained oonristentlp and rapidly, ua8 taken aa lndb sting the end of the fro&net. 10 ham not, thWOfOr8, (LB 78t, and in the imrmdiat8 . . . i future may not have, data aa to tbrr frequancy of recumenoo, although it ir hoped that the follorr-up hiOtOri88 pay be obtained on at loaot ;pati of our discharged ptiOllt8. The7 bav8 all b8en inrtructsd to return to U8 on th8ir return to %aw York. It is probable that a aonsiderable number of navy men may ha thue kept under obrervat ion. 2. For the Riven rate of administration. the auertiozr -8 raised a6 to whether a cure could be effected more quickly when the drug was dleeolved in 2 114 f&8CUlee than when it was dissolved in 1 moleculp. The animal experi- manta of Dre. Brown and Pearce had indicated that only l/2 to L/3 as much drug WLLE required for a cure when a larger amount of alkali was used. Our' reeulte bve shown no differences whatever in th8 therapeutic ef fsct, whether the drug 1~s diesolved in 2 l/4 or 1 raolecule of alkali. Of sixteen camea trented with 1 moleoule of alkali, the average time to&red for negative Pa888nnann wa8 42 days. Of ninstoea oases treated with 2 l/4 molecul8o, the average t iae was 47 dayr. 3. The queetlon wae aleo rai8ed a8 to whether tha adminirtration of the drun with 8xcsrsipe alkali. namely 2 l/4 molecules. diminirrher the toxio effect in man. The foElowing toxic effectr wets noted for a reCord when they oaourred in the caaee Under each mode of treatment: Thrombosis, abdominal paln, fever, chill, headache, nausea, vomiting, appearance of albrrmin or cute. Of these there was no marked differences in the two series except in thrombosis. Ths oaurtic effect of alkali, when 2 l/4 molecule8 war8 used, resulted in,thrOntbO8i8 after 91 per osnt of the lnjsotionr, while, when only 1 rcolrculs Of alkali Wa8 u88d, throlnbO8i8 oacurrcrd fo11OWing Only 1.5 per 08Zit Of th8 iIl- i : : jsct ion8. Ths other sffectr may be noted by reference to th8 tab18 below. 1 Tab18 I. Relative therapeutic effect8 of A 189 dissolved in .-I ,. `. J and in 2 l/4 moleculee of NaOH. 1 2 l/4 siolr. No. cases treated with open 188ionr. 31, 25. Av8rsge no. days until lesiona hsalsd. 7.8 10.9 IJo. cases treated with positir8 U. R. 16 19 Avsrags no. days until F. R. becam6 n8gative 42 4'1 Table II. Relative toxic 8ffects of A 189 dissolved in 1 and 2 l/4 molecules of NaOH. . .I * i' ( 1 mol. 2 1/4 lG018. Total no. cases treated. (1) ' 34 37 Percentage of casea shoring adominal pain at caome rtrgs of treatRent. 41t2) Total no* of injsotions. 197 Percentage d injectionr followed by thrombosis. 1.5 a II a n a f8VSf. 14. I a a I " chill. 2.9 I a a (I n headache. 9.2 a I) I II a nau808. 5.8 5. a m 0 a " romiting. 4.8 a a I m o albumin or UaStS. 12.1 16 217 21.0 24. 17.5 12.4 11.5 6.0 25.8 (1) Only 71 of our osles hat8 been tnstsd throughout purely with either 1 or 2 l/4 moleculee of alkali. Of the remainder many have boon start- ed with 2 l/4 moleculer, and during the treatment ohangsd to 1 rolecule, because their reins were ssnoitivs to alkali and thrombo8i8 kgularly followed the in- fSCtiOn8. Suoh aam, are not includad'in the table. If they w&e, the psr- CentagO of thrmbo& rOeoid8d against. the'lj/l/4 aoleokle treatment in Table 11 would be inarwwd.' ' * . '. (i) The'oa~~e oi t'hi8 hi& pil'tJdnt4. Of p&AS 18 that 21 Of the 34 ' ,: I, a808 on 1 o olsuulo lkOE'~oeived ti(4. dri& at &o rate of 10 mg. per kilo ekrf . ' 5 daf8. $One of tkii 2 1/4 tiO18UU10 CaS88 wakiwd it a8 rupidly. Among 08808 receiving the drug at the e&e rats ths percentage of abdominal pains 18 about the 8tuw, whether it is given in 1 or 2 l/4 molecule8 of BaOH. With the dosage ChOSOn a8 the optimum, 7 ag. per kilo every 7 day8 the pains re~dom OCCUr with either 1 or 2 l/4 moleculee NaOH. Among theme effeots the abdominal pain is srpr~ially 5, `jl n important. It apparently occurs from administering the drug in darer of 10 ag. per kilo too cl~ealy together. When the dore mentioned preriourly of 7 mg. of drug per kilo body weight once per reek ir given, abdominal orampe are reldom obtained. When the dooage rae increaeed to 10 mg. per kilo body weight ever7 five daye, orampr rerulted in more than ons half of the CBIO~. They were extremely painful, oplio, and might occur within a few houre or creveral dam after tho lart injection. In no O(LIM, however, did examination of the urine indicate kidney injury, nor could any offset on the heart aotion be detected . by the electrooardiogram even during the attack. All patientr hating cmmpr recovered. In no oam was then evidence of penumsnt injury. 4. &&.!!m rapidity in which the drug oan be rdminirtered with rafatx. Thir point hacr been oonrldered in paragraphr 1 and 3. 5. mtiu. Routine axaminatione of tha urine have been oarried on twioo IL wrok on every patient under obaexntion, and in moot oabee the kidney function hu been alao examined once a week by t%e phsnol- rulphonphthalein o xoretioa nethod and by biweekly detenaination of the blood urea. Ocousionally Blight albumin and oastr hare been o ncountorod, but only in one oaaa war real kidney injury detem&i&bla. Thir patient had &eeiied about 7 graar of the drug, and rfter'tha krt dare ruddmly developed an~rir, He was treated by Ds. St+die in the.-r utilired for handling pat ienta kith biohloride podsoning aad moowerad completely. _. 6. mot of the ;Qoao;on heart aHA= . Eleotrocardiogrema were taken ot the patientr during the `lnjeotion of the drug, and at whtrrer other time8 promieed to be of interest; erpsuially during and after abdominal pain8 re- fsrred to above. The drug had no rffeot on the electrocardiogram, but an interesting abnornrrllty was noted in a considrable percentage of the o fphilit- ic8 who came to ue for treatment. Out of 85 ccuea observed, 35 showed a split T-wave in the third lead. Thin phenomenon indicate8 8ome aortic involvement. So far as 18 krqu, thir phenomenon has never before baen observed. It wae noted that this notoh disappeared after the Usrrertnann became negative. The exact cause of thir obrmgo 18 not at preeent clrar, but we hope to continue the rtudy of thir phenawmon. It may be of intereat to know here that this notch- ing ol the T-wave wa6 obrsrved in a oonvaloraing pneumonia patient who, upon exslpination, rhowed a four plur Wassentmnn. Another oaae war sent in by a doc- tor from Yontolsir who found this notch and wa8 unable to explain it. 8ub8e- quent examination of th8 blood ehowed a four plus Va88ermann. 7. Rate of eltiinatioa of aroenio rdminirtered m A 189. A practical method for the detemination of ananic in ths urine and feces was worked out. It waa found that about o qarl amounts of arrenic are eliminatad by the kidney and ths 1at.0tln.0. IPldnatim begina immiistely after injeatian m$ an ruccreding days bocanor gradually rlorrar. Within throa rrsokr aftor th8 mart rapid trmatmmnt, ths 8lbination ba8 practiaall~ C8a8ebr Similar oxmotion experimmtr wore perforrwd od rabbits, and thrir tirsuao wore awlymed at varying periods after the inJ"otion of l+.rge dome8 OiA 189. ' Ths anlarlr also SD abuut tthrro meka ihowb r~~~xbruM~ aanplatr o oo?o*??????? . It was bpocrirllp intetirting to note tb;rrt when o l@ination kr tlm url& atoppod; no a& arsenic could bo `imad in the tls- a&i. `3!Ur iridicat.8 thst the w i8 not o tored in the tl88w8, but 1, ,. oaD@lotrl~kmi.~~ aKib tiuit:riha 1t $8 not"ginn too trpidl,,' t&e ir probably no tiger of acxumul~tin offrot. 8. T& dirtributlm of a&nic in the ti8srrer 09 rabbit'8 aftar tha injection .of A 1es -8 8~tpdi*. It wag found that tba dang accuxunlater o ????o? ?* ??? o??????? The lungm, kidnap, intmtinom, aad nruscle8 aoa)- tained lore arsenic tbn tb liver. Tin admldstratton of th8 drug with 3 molectilo8 of alkali as ccutpared with 1 molecule had no effect on either di8tFibIltiOA 01: rat0 Of SlimirIatiOn Of tba ar88niC, 8xCept when Tsry masain dome worn girrn. Thm on0 o xc8p tion was noted when the trenmndoue dole, IUMIU~~ 150 mg. per kllo, WaS iq)sctsd. Whan this dare was given with mly 1 molocul8 of the alkaLi, largs 8mduntr of ar8onic wer8 found in the lungs, apparantlp becmss th8 drug uas pncipitatod in tbs blood and stopped by tha capillarlee of ths lungr. Whmn 3 molwulee of ulkali word given, this . did not occur. It oocurrod with OIW molrcule only when the above KELSS~V~ tset uaa given, not wh8n dorer cmparrblo with thO88 ased th8rapmtically worn given. Ihen nhen ths does8 w8n am high a8 60 mg. pm kilo or 7 timea the therapeutic doss adopted for mm, thsm wa8 no accumlation in ths lung8. In ruch doers the occarional a&all wa8 without my effect on the d~stribu- tlon of the drug cm the body. 9. lcho h?iSSRWUUl rMOtiOn8 ware followed at W88kly intOZ'V&S & at loart two l&borrtoriee. At first the blood specimens were SSUt to th8 Board of Health labo&tory and Dr. Jag18. Since then, howmv8r, the facilitior for psrfonning our bwn ~srermann reactions mro d8wloped, and the reeults obtained from theso laboratorios are compand With thorn0 Of Dr. Jsrgl8'8. Atpmrsntrrs arr nly$agopoa Qar own&~8mmmm8 88 th8 t8&lIi@W -8 derelopmd ta 8uch 8 point that thr la-t8 beaam8 thoraughly conkstent. 8' 10. l&&s-fiold d#t4BrPainrrtiaP38. b8iOm are regularly exmnixmd for 8pirOCht88 by th0 debk~f iold. On8 of the probl&s at pr8semt under iWBSti@StioIl cQD3Cems the length of time which 0bp8.8 aftor tb iirrt 11. charting the roslllts. &art8 mm printed in detail tab- in ulatu concise fom, both laboratory rrnd clinic& data, briagirq out al% PLANS FOR THE IYLMEDIATE RJ!lVB. At preeent the following plum seerm to be acceptable: A dosage of about 7 mg. A 189 per kilo body weight weekly ia the optimum. It I@ seldom followed by abdominal p&n or other aerioue effectr, and re- preasntta a umxlmum r&to of rdmlni8tratlon. It lr poseible to InJect this amount with only 1 molecule of alkali ainco larger amuntr remit in in- cremed percentage of thromborir without apparent affect in either lncrear- ing therapeutic power or dmraaaing toxicity. The follting problrms resm to be the next demnding rolution: 1. Tha optima cancentratlon for tb adminirtratioa of tb drag . Thu far tb6 caumntration haa bean varied fraa 1:lOOO to ItlSOwithout apparent affect 013 tbrapeutla power or toxic action. If tb drug is utiliud for military grrrporer on a wlda (I&O, it may be maw- o ??? under aam caulltlona to give it a man concentrated form rrith a 8yringa if it Is gimLl rt rll. Cmreqwrltl~ (I, &?a crmtixllally increauiag concon- tration in W&r to diminirh tIm volxtm. of solution injooteds. in order to detomira the greatest caausntntlonwhlch prap be given with rdety without rffeeting the tiherapeutio rlmlltr. ., `2,. Cambinatisn of A 189 I*ith mermxm. `Sinw it 18 glenemlly bsld that tM boat rmmlts tith mlvarua ati. obtained wbsn km treatment in relnforrmd with ppbraary, m ma attmpting to find whet&r the ldmb is true tith A 189. Coaseqwntly ? o eriee of caue~ have been rbrkd Qmb axa receiving A 189 aad rkuultaneaul~ bichloride and mrcury intr8mmCw larly . At preeent with tb `data which we alrsadg bara QJ1 w th@ MIPlk8 fran thme cues &cmld indicate rrlthin (L few wadko whether tb mfoory rliortem tb8 pertab rm@$r.d to obtain a neeptln Waarsrmm~~ 3. Coarpariaon with aalvsnan. After the appropriate mode of adudniatrring A 189 bar been ascertained, it appears dealrsbls to ccmpare it in the am@ wards with aalraraan on a sufficient mmbar of cases to get aatiafactory data on which a comparison of the pasallrr msrlts end dfaadrtuitagea of oath drug ml@ be tasted. 4. Ths world thua far baa been pqoasly limited for the moat part to primary and o ecandary caa~a*. It la now being extendsd to nervma, tartlary, and congenital ayphills. 5. We have been unable to find in the literature or in consulting with qphllologists any accurate date am to ??? o ????? neuro- mAdive. It, therefore, soems advisable in our treatment of au primwy and o ocondmy c&a08 to do lumbar puncturo before, in the aklddle, rad at tb end of our treatment in arch cam, in order that thir iiqportrrnt qusstlm may be settled. 6. It 18 a2r prposs to ocmtinur the eloctro- cardiogreph study mentioned abovo in order to clear up the catme of the anaumly noted and alao to find art,lf possible, whether this leap ba a ratbr iwortant diagaoa tic point in early vascular syphilis. SUhfMARY OF CAN!3 TEEATED FITH A 149 JLwdRf 1 - OCTOBER 1, 1918. 1. h'o. of O~B~B treated 2. (I I) 8 discberged ~BBCII?WUUI negative 3 o ? o ? ? ???? tiV@ 4. I n m under obsematlon 5. a I o disd 128 45 25 57 128 In the 25 came5 discharged -uith pOBitiv0 ~~550~ PBtbCtiOXLB, One refused Sufficient treatment, twsntp wera discharged ae unsuitable CQBOB for obaer?ation, end four were diachargwd for disciplinary I'O~OllB. The one death was In a case who died within four hmt8 of 8dmla- sion, bafore treatmsnt. Tbo cause of death as mvealrd by autopsy was due to cardio-vascular failure, rsaulting probably from diphtheria, .