ro Iliii CCJH~'OR~;I'ION OF THE ROCKE,FELLE.R INSTITUTE FOR MEDICAL RtSizARCtl OCTOBER, l-317 THEBosPI!EAL RuftlB Cole Chngar In the Stnff. The entrance of our country into the war har led to the departure of a number of the mrrcberr of the Eoepltal St&f, to uxxlertake dutlem In connootion rrith the Azmy. Those V&LO have been called dlrectlr to this rrnlce are Do&ore Chewier, Fits, Morton, Larron and Yorlron. Dr. Chesney Jolnrd the Hospital Unit of Iaahingtoa Unlverrity and ir now with thlr knit in Fmnco. Rerioualy he had acoepted M appointment ar Aualrtnnt Proforror of Mdiolne In thir Unlrorritp, his uexvlce to begin thlr autumn, and he hae therefore permanktly sewred his oonnection with thi8 InatitUt8. Doctor@ Fits rai Morton Joined the Harvard Bars Hospital Unit No.0, and are aloonor in a&ire eonice la France. Dr. brron Joined the Medical Offloer~r Beaene Corpr exml '~llae ordered to Fort Bengamin Harrimoa Dr. Morieon almo Joined tha Nedlcal Officer' a Bersne Cop and utar de- tailed by the Surgeon General to join the rtaff of the Hospital for Cardlau Mrsaser of the Britlrh lyddlcal- Serolce In London. _ In addition:>to theae'men, *o havr enterd active mi$itary 'I' aexv1u0, Dr.~~Fklmer bar-left to:sreirt,:Dr:~loagcope In-thi.teachlng of,':,.: mebical~rtudontr'at the*Cgllege~of Physician; and Surgeons... Dr. mr<:'... hm~rotmlvmd an appointment'ar Amistant Proferror of Medlaine at Corn011 i Medical School, but will not take up his work thera untll'after the uloro of the w. Durbg the part year, in addition to the regular rtaff, four voluntary workerr have -been engaged in the study of problala relating to the diasassr un&r ixwestigetlon. There mentare Dr. Emert Stillman, .J!' f3q Doctors Blake, Levine and Imndrgaard. Dr. Stillman has rebeloed an appolat- msnt on the regular staff of tha aospltal for next yeubr. Dr.Blakehas . been appointed Asslrtmt Profesoor of Medicine at the Unlverslty of Ylnn- eeots, and has already oomnenced his work there. Dr. Levine ha8 entered the Medical Officers' Reserve Corps and has been detailed to tha Hoepltsl for Cardim Diseases of the British YeUcal Semlce la Imdon. Dr. Lunde- gaami will shortly return to DerrPark to again taks up his studies In the Unlvemlty lh Copenhagen. It amy be seen from the above that very serious inroada have been made into the working staff of this Hospl tal. This, however, rraa to be expatul, and It Is a source of mtlrfactlon that the Hosgltal has been able to furnish so msny men resdy for active service. Yoreover, during the year, and especlall~ during the present stmner, a mmber of thr mn have bssn engaged in aotlvltler w2dch are not dlreotly relrtad to the solentlflo lnvostlgatlons of the Hospital, bat which are of aid to the Nation or to the Stata. Dr. Douher wan given leave of absence during the months of Jannary, F'ebnmy and March to acoampany .,. tie; of sxmy mubal`offloers oamer& pneumonia, and in tsrohiag them .,' `- the aat$rl method8 to be employed in dwsis and treatment of thir direma. The Surgeon General* hrr also reqpert&l Dr. Cohn `to hstm& a mrpb& of of- :> floors of the Modlml Beson~ Co&s ti &s teehtdqw of &&atloa of iho Y .' audio-vascular system. In ooinpllance wlth thls request, a mmber of of- ' fleers detailed here for thle purpose are now being given a course of ln- structlon by Dr. Cohn. Dr. Van PLlyke has spent the months of Jnly ad Augmt at the LaborstoCy of the Hooper Pomdatlon at 8sn B'ranclsoo . He has gOhe there rt the lnvltrtlon of ths Mrector to danonrtrate to the msmbsrr of the staff of that Institution nsw chmnlcal methods which have been devel- oped In this hospital under Dr. Van Slyka's dlreotlon. Through the hSn&ess of the State Board of Hsalth, Dr. Stillman had the opportunity last winter of Investigating seveml small spldmnlcs of pneuraonis occnrrlng throughout the 8trts. This study gwe us umch Information concerning the mode of spread of thlr dlsame. 3~lentlflo Report. Aante Lobr Pneumonia. During the pa&t tinter, 133 caqes of lobar pneumonia were truted in this hospital, mnklng a total of 529 cases that huve been stud- led hare. Of these, 438 have boon shown to be due to Pneumococcus, and the type of lnfeatlng organism has been determined. 161 of these aa~88 were due to Pneumoooocus Type I, X33 ware due to Pneunocoocus Type II, 59 were due to Pnmasooocau~ Typ III and 95 were due to Pneumococcus Type IV. 108 -sea Of . Type I Info&Ion have ,beon treated wlth amam, with 8 deaths, 34 maem. Were treated dpring the' put `tinter, arxl only' 2 died; and one of three fatal oases -proved to be- aompllcrtod by.elct+nrive and aulvmiced tabemulorlr. The reaultr of somm troatmeat~ixa this"type of 0110, thereforei hews' aontimd to be es- oellont .' 8iadlir 'iwults have been obtalnod else~ere. MaJoir bTichols has lrts ly reported the treatment of 45 cdrwm atmng the t roopr on the Tens `( bordir ulth only 8% mortalty. This Wo* relating to pnmmonia ha* been oarried on in three directions during the past yew. First, attm#a hne been mde to render 4 the general routine treatment of patients tith Type I Infection more prac- tical and convenient. Second, further studlee hene been msde concerning the eFIdemlology of the disease, In th8 hope of devising rmasurea for lower- ing its vsehigh lncldenoe. Third, studies concerning the mods of action of the etlologlc agent have b%an contlrmed. The need for d%tenEining the etlologlc agent In every case of pneumonia before serum treatment Is undertaken prevents to some sxtent the general mployment of thlr method. Where the laboratory arrangsmsnts for making such determinations can be property organlrsd, however, the dlfflcul- ties are raslly not great; the m&hod 1s neither camplox nor difficult. It P has been thought however, that an accurate standardlsatlon and descrlytion of the msthod would aid In Its gonoral a@oyment, and this has been made by Dr. Blake. ( "Yethods f or the Detemlnatloa of Pneumococcus Typs~"`, Jour. hp. Mad., 1917, xxvi, 67). Doahss and Avery have danonstrated that aem frequently occur ln the blood and urine of patients with pnaumonla, so that If oamples of these be mixed with spscifla Wmne se- prsclpltatloa oocurs. ThiB fact may be made use of In the dlagnosls of the two of Infection. (Dochex and Avery; `The Elabomtion of @eciflo Soluble Subataaoes~by Pneumocoocus during Groiihs a Jour. Xx&. Mid 3 . .".. ..", ;; ._ .* ..:.`:i. , , October, 1917 .) All that, Is nsoessrry Is to mix ." i ,. . .; A': &' ,. ~. ; : * ;. ,. :..s ,-I> ._ i' __ ,: . . . . . + i ,:; 4 ;I,, .m , *..z ; !on small amour&e of the urine and equal quantltles of the various imnans usra. i" .,I _ .,.. ,9 :\ :, `, ;. *?, I . k i' . . ,`I . \;.. : ,. ..:`Lit a. 2'. .,, . . ; `, `A -;: ..&...lflJ `I 2.' - .x .3lr! A reaction occurring in one of those mixtures indicates that th; Infection _I..' ., , -I) `,,*. ., .:> 1, ?A...&.! , :I, .:;`:, ,r.,:, ,. I * Is due to. the o sa~ type of Fnmmoaoacus ~8 that rmp)oyed In producing the .,* . *_' ., $ _,." `. ,..6 .P `I , :: ., T _ r `:' *, 1 I ,T .`*.r$ `.`/i;' ;:f q'p,FI';.% SO~IB with which the reacbion occurs. In certain cases t'bs dlagnos~s of `. .,, .,,., .i 1.. *a.. b -\ w* (' , ,' :.: ,r .,a ,, ,,,_ ~ n ,* :i ,iiY#> -$a type may be am&e by this method rdthmt any trouble and almost it once, The ., -_ ., appllcablllty of the method for diagnostio~purposes, however, 1s limited by , the fact that the reaction occurs In only about one third of the cPses, `in L those more rwerely Infected, and sspeclally late In the disease. Notwlth- stanglng this drawback, however, the P]btho& Is of consldersblo practical value. , Effortr have aloo been made to detemlne more aocurately the beet method of admlnlrtrntlon of o enm, the proper dosage and fraqusoluy of treatment* . 8tuclier on animals and obrervationr nwdo in patienta during the part winter have rhown thnt, after lnfectlon has lasted for rome time, sab- rtancer are found in the prtient'r blood which nentrallre the imaMlty p&i- clpleo in the horee aeru~. (Cole, Vhe leutrdllration of Antlpnfsumococcuu Irmuuna Bodies by Infected Mt.8 and Saraa, Jour. Up.. Med., October,1917). This faut rttlkingly empharira8 what ha8 pravlotlrly bean inrirted won; namely, thst the treatment 8hould be cmenoed early and large darer of serum rhould be anployed. Simplification and improvement in the mattei. of product ion of the o ennn and lmprorauent of rm thodr of rtandardiratlon have baan needed, and the80 problem8 have been rtudied during the prrt winter. The old method of Mslng hot8er uonslrted la the weekly injection of cultarem ti increasing rirb, first of dead, then of living baut8r.b. To prodacs high grader of lm- munlty, It hu been thought necersary to ?ae very hrge darer. Studiem made daring the past y-r have shown that the lnnmmlzation of horreo can be much more ropldly ~uompli8hed'bymking inJaqtion8 of small dole8 every day on alt&nati w&a. ,, `. `; _,,I r). ,I , L'eL'yi ha8 been ah&n tlk'laria doiee of &.ht,e, mush am for the~peu310'~~ores should` conform. During the prt `wintkr the various antipneumococcic o e= produced by ktzufacturers la thir country wore tested, and mo8t of than were~found to hawe little or no cantent in antibodfer iOr . h. ,< . II '\ $`+ Type I pneumococcl. We have therefora worked out a mthod of standardization which we believe is as sstisfsctory as it can be made with our present know- ledge, and we have racotPmended that the Eiygianio Laboratory of the Public Haalth Service requira that all antipneumococcus rars #Old for therspeutli purposea meet the requirement9 that we have laid down. Major McCoy, Director of this Laborutory, bar v'bry luPillingly cdoperated with us in this mtter, amI It ir believed that all the serum employed by the Army, at least, will be of 8atirfactory potency. The production of serum of Type X In fairly large amounts is now under way at the fans in Prln0eton, and the production of thi8 merun at the Institute ham been dircontirmed. The 8tUdieS aonNming the epldamlology Of pneUUOnia baVe proved of great Interest and have ylelded reenltr whl&, it is hoped, afford a baSi8 for instituting ratio-1 preventive mea8urea. Up to the tima theme StUdi were pndO&&en, it war believed that iUfection in pnmonia is au- togenonr; that is, pereons having pneumonia are infected with the organiarlrp they habitually carry in their mouths, the reason for much Infection being a lowered genaral or focal resirtanue On the part of the ptioat. The ob8erva- tiom nnde here have brot@t strildng eviderme agaixmt this assumption, at. leaat as far am paeuuonia due to Type f and Type 11 pneunoco~ci .ia concerned, L `pbO$`, 8tI'O@y SU&(Oet $K%t pII8IXSQnis,.~at +LSt; Of thO80 tWQ typ4W, doer ,nOt, II 3diffrrrln thi8,:~e8pe~t,f~~lQther;iniecti~8 di#ea#e#, and~thlt,infeotlon ia iIl QlQSO GQntaCt ;rrith 8UCh patient@. :- The vfhrletier of pnamppoaoaal fmmd,in~ the mouths of pnknia patient8 &wing convalesceme have also been o ??????? d &to t&m Q&MB@ of pnmmococci found In the dust of mam8 occupied by 7 7% pneumonia patients, aLo well am those In the dust of rooma not inhabited by such persons. Without going Into the detail8 of the study, It may be rtatod that pneumococai of Types I and If ara practically never found in the mouths of henlthy persons not In contact with pneumonia patiente, al- though thaae two types of organirmr cau8e over 60$ of the cases of gneu- mania. On the other band, a conrlderqble peroentago of permona llolng in . close oontlrct with pneumonia patients, erpecislly manbJre of the family or friend8 who have cared for these patiantr, are fo\rrd to carry 0&ani@m@ Of the80 tSye8, the type of organism found in the carrier being always that canring tha disease of the patient. !ieithar the patients nor there healthy carriers, however, carry pneumococcl of there types permanently. Ueually the88 type8 Of ~xIWUKK~QOC~ disappear in thlse t0 fOUr WeekB, sad o itbbr no pnetznococal are then found, or if peasant, they are of the type ccxmnonly found in healthy mouths, Type IV. Yinally, pnvmnococcl of Typev I and II are not oomnonly found in duet, but thay my be prerent in the duet of rooms occupied by pnmmo& patients, oomaler~ents, or healthy carrlera. All this midermo stron@y indicates that info&Ion in pneui moniaLi8 not &t&m&us, bit that `thv orgerrhaai are `r&birfid by ihd; p%tivn! In any case, in order to reduce the vsry grest prevalence +,`. I of pnewnonla, measures similar to thoee employed to prevent the epread of b othar infectloue dlseasas should be instituted. This will be eapeclally important In the came of t roops,for pneumonls ordinarily occurs iith great lntsn8Ity among raw recrulte, and it 18 to be fearad that, unleee preven- tive mesru~ can be instituted, the hl8tory of thle direare in our own National Army will be the mama a8 that in other arm188 and in other warm. Another po88ible method for prtwenting the oacurrence of pneumonia 18 by the Qlployment of prophylactic vaccination. Thir does not sem prvotlcal In civilian populations, but among troops, where the dlcleare 18 likely to be wideapt&, thi8 method should be considered. Con8id3rabl8 work ha8 already been done in lnveetigrting whether or sot this procedure would be likely to be suace8rfW and if so, In devirlng the bO8t method8 for carrying it out. A number of problanr are still TJ.nSOttlOd, but sane of the80 are under lnvsetlgation by Dr. Chlckering at the present time, and it la planned to continue thir investigation daring the autumn. Since It is very important that the present knowledge concern- ing 8erum treatment end prevention of pneumonia should be readily available, this has been colleoted in a pamphlet which it is hoped will `be ready for :,J , " :.c- di8tribUtiQAAbefore this mv6ting of the Boa&b IA this -let .ia given : ,. i* ., ,` `. .,. t J :. ..* ..,::.. / a detailed ard practioal &ercription ,ofLimthods anployed. I ) ;~-;.::?.`i ,* I L Among the,eqperimental and theorstiu~~8tudi88 ~orrroming .5'" i&' . ..`.. ,. ; :, \ j . . I., :a* _. ,. . ,: ::. 8: f ' - pnvtmonia that have been aarri4d on during the $art year, arid0 fro81 th#r . % . .;. , .Gj .% `< . IC . , 1 :-, ,,.a\. - ,t:i a i i&e6 alrsrdjmentlonrd, ham been thorns of Dr. Donher; and Dr. Avery raacernlng r. .:I. ,L Y. .' . > ! ,. `. the nature of' the preclpltable subata&e arising &ring-the growth of f 1.7, ,' 1 pnmcoacl, both within and outside the'body. The porribl6 a& of thii \ i : . substance in the intorieation of the dir&me ham been investigated. Dr. : Blake ha8 also made further rtudl.8 COnCerIhg ro-cslled "antib~#tiQ' I 9 . iumtmlty, and Dr. Palmer has studied the question of the increased acidity of the urine In pnaunz3nla. These atudles are of much theoretical intsrest, but ara not at pressat-applicable to the practical problan relating to this disease. Heart Dlseasa. Thp work during the yeax has included a contlnustlon of that pretlourly carried on, having In oiow the lmprovapent of the msthods of treating heart disease, espealally the methods of using dIgItAllo. In addltlon to this wwk, the folloting specific problems htr been studlad: 1. XstImatIon of blood premare In patientr with fibrillat- ing aariclos. In such persons the pnlra beatr ara not only vary irregular In time, but are alro of wry uaequsl force. In ordlnarf msawure=entr of blood pressurn, the method anployed consistr in estimation of the force of the pulse beats. Since In flbrlllatlon no two of these beats my be equal, It Is evident that the ordinary methods are not applicable; To overcome thb difficulty, the attanpt has been made to estimate the pressure by determining the mmber of beats at each of ieveral levels of pressure, and obtaining an the aurlales are made to fibrillate. To estimate thnd blood pressure in uan at a corresponding level of the arterial tree, usz has been made of the Qtlrtnar tonoxneter, which was formerly used In estlmat lq blood pree sure, but tiich hea bean given up for other methods which are more con- venlent . Studies on a large muber of patients and no1~~1 persona have now been made in this hospital, and It hss beendemonstrated that it Is possible to make accurate readinga with this lnmtrunent, and that by thls method canelrtent and accumta detalmlnat ion of the @`effect Ive" blood pressure can be made In patients ulth aurlcular fibrillation. IX. Dr. Levine hae carried on a series of experimental o tudles to detennlne *ether the occurrmnce of digitalis effect, on the heart 18 dependoat upon a cortala concrntration of the drclg in the blood passing through the heart, or *ether this occurrence depends upon the actual amount of the drug which has been absorbed by the heart mumcle, even though the dmq Ia tiinlstered very alowly. Thlr point Is of con- rlderab~ Importance In connection with the problm of dlgitallr dosage. (. In those studlee cate have been used, and in the mame cat the results fol- lowing varloue~ methodr of adminIstratIon hsre been obsemed. It has not `,`: : been posrlble to obtain as complete ,molution of the problezP, but the rtud- 5 !IOB bdkate~ .that? both `the, totallaammt~ oft,,the .drug adminirtorrd and:itmd ' `. . .: 5 !rT `- 111. t Dr.% Moriron `bade -the very intdrertlng obrenatldn-.: . that eleutrooardiograma taken before and rftirr phlebotany rhowed oortalna difforencao. It wae thought that ~theme differsncem might be dependent WOP blood voltlp30,. end he her pydo a reriem of experimental o tudler In anlmsls and ha6 mad8 mznerou~ obsenations in patIoate t0 determine the s `,)-- .,d exact effacts, If any, which changes In blood volmm came in the electro- cardiograph, It han actually bean found porslkieto produce changes in the 8lectrocardlograms of animala, 8-116 ah0 Of ptientr, by producing Chmg86 In blood roluns by the adminlrtratlon of very large amonat s of water or by sweating end freezing. Observations on the blood, made at the same time, by Dr. Palmar, honed that actual chmga. in oolrme took place. Thea. stud- ier are of value in explrlning the form of the sleotro-csrdlograph, ooa- coming tilch there are aaveral theorlea. IV. Xkrly in the year Dr. kundemrd undertook certain stud- lee haring for thdr purpose the development of a method for detennlnlng the rate of blood flow, or the minute volume of the heart output. Before coming here, Dr. Lundsgaard bad conducted Important InvostIgatIonr on this problem aad had found that, whll. accurate results could be obtained by the method dwlred by Krogh aad Llndhard, thl. method ms not .ulted to clinical ln- re.tlgatIoa. It seaned possible that InformatIon could be obtained coacern- lng ths rate of blood flow by comparing the difference between the oxygen content of the arterial and the venous blood. If the metabolism la constant, the amouat of oxygea .rmored from the blood is i~8~eiy.ptopO~IO~l to the rate of flow of the blood throua the capillaries, Before aay practical i use of this principle could be made, honwer, it ha8 been neceeury to ob- tain much,aew &siological data,. for the matter 18 much more canpler than .i I the rImpl8 statement above might lndioate. So far as thl. method of 0.0 "' ' , timatlng rste'of bldod flow Is itrelf coakeraed, it $8 too o ooato say how great it. ollnical rblu. ppry be. !Phi itmiles on patients a0 far made in- dlcata &at, ae a mtkns'of 8stImutI& the chaages in the ratb of blood,flow in the 8ame iadIVIdua1 (as during compeasatioa'aad during decompenaation), . . w 8 .`a - F ., ,. the method gives very intaraating and instnztive results. Whether absoluie' stmdarde can ba obtained which hold good for different lndlvIduals, is not yet certain. At any rate, however, the method promises to have conslderablr valua for clinical study. Moreovar, out of this work has developed another llna,of lnveatl~tIon with very practical resulte. v. In the course of the preceding lnvertl~tlon it uvu found lmportant to have methods for the ready detexv$natlon of the fanctlonal lung , volume in any lndlvldual. Dr. Lundsgaard and Dr. Van Slyke have therefore carried on an lavestIgatIon to determine whether or not In nolmpl persons there is a constnnt relationship between the lung ro1ume and the chest ~01~~8. The lung volmne Is detanrlned by mearumnent of pulmonary gas exchange, and the chest volume lo dotenclned by sImy10 actual meamurements of th9 cheat wall. From the rtudy of a large number of N)IYY& persons It ham been pas- slble to show that there la such a constant relationship. From the chart volune, thersiora, It Is poemlble to calculate &at the no&l lung volnae should be. A aerIe of patients tith tuberculorls were then rtodied through tha klndnero and with the assistance of Dr'. Oarvln of the State Sanitarium for Tubarculorlta at Baybrook. In the& patient8 the actwl lung ~011~n8, 88 determined by phpiOlOgiCai methodo,~ was compsred with the lung volbe am ! calcula~~d.from. the cheat XIe+SUrm8ntS,-~,+8rg int8r8Sting r8SIdtS W8r8 obtained, :,It se~r,t~t,,by,~Is,me~hod~,the portion of ,,lung tlrsw: falling to functionate-oaa be, .at ~leart~roughly, detemrlaed. _. p `. ! .,.' `.r- Duril3g the pear Dr. Allen `has continued &d extentied hii studies concerning the disturbance of the metabollmof fat In diabetes, which were nmntioned in the &at a.nmxsl report. Thee0 8tudIes confirm the view that in the dIab8tIc organism fats and llgolde are lese readily taken 13 up by the cells from the blood, than they are In the no-1 Individual. In diabeterr there Is a primary and epeclfic impairment In the metabolism of fat, ae there Is of carbohydrates. These studies furnish further evidence that diets of low protein aul high fat, such aa were yravlously recamneaded for diabetics, ar9 improper, and It has been shown In animals that slmller diets may even induce a fatal outcar;e. During the year much study har beer. given to the anatomical changes In the pancrear occurrlng in dlabetee. The large amount of material obtained from dogs In which diabetes has been erperlmontally produced, az wall as a considerable amount of human wthological material which Dr. Allen has collected fran thlr and other hoopitalo, har rendered thir o tudy par- . Bible. Ever rlnco the demonrtrat ion of pthological changer In the pancreas, orpecially in the lrlands of Langerhanz, in certain cazez of diabetes, there has bson much confbrlon concerning the relation of there changea to the dlr- 0808. Certain pathologist@ have even denied thit the pancreatic changes WC3 of any 8IgnIfIcanCO. One roaaon for thla confuzion and doubt has been that in certain ca1~08 littie or no alteration ha8 been present, and that In general there haa seemed little relationship between the extent of the al- teration and thb' severity of the dieeae`e:' It has `hdw `bock shown that'iri"' ' ' orperimental' dkboter in' anImala, rpebific changes in ihe cells of the l~lmds if' ia,&;r&8'db .occur. ' I'. : j ; .. ,"", Those ciinger oonsirt of vaiiolizetion and'de~ki&&ion, and the intoneity ir psrallol to the clinical couxva of : : T, the diaeaae. 7 ,,:' ",-, . ; .,' t",.. halo rhown that an unezijectedly high &&kl&"of `&ire shb&;"iklar ,,_ ..I - changes. Thbre c&&k a&"not rtrlkiig, I$Uat bi ee&ched for, a&`@era undoubtedly formerly overlooked., One reason for thir Is that the tissker I , `. wore usually not flxei eufflclentIy fresh. By mean8 of the& changes It ha8 frequently been porsible to decide from the' elreminatlon of the panareaa alope that the patient had suffered from dlabat OS. lPheso changes, however, are not recognlesblo In the milder cosos. Tnls otstamant tlon of tha terms mild and severe. Dr. Allen thinks that b--lb> .d : L " raquirao a def ini- whether a caee Ie . mild or severe can only be detsntilnod by the reaction to proper treatment. Certain cases, oapeclally In the young, of apparently grst eevorit y may improve very amch under proper treatment 9nd acquire even high carbohydraio tolarsnco. Buch case8 are raslly mild, although wlt'n high fat feeding such patient6 might have died very quickly In, coma. In such 2 caee the finding of little or no change In the pancreas would not be an argument a¬ the r%olo of the panoroatlo changeo in thir direA8e. Dr. Allen thinke that, If tha pathOlO@Cal changes are intergretod in the light of the new knotilsdgo concerning the clinical course of and functions1 chanqee in thir di8Mb80, a parallolIam beoomer apparent. Dr. Fits hr completed a rtudy coincierning the ur01~ index la diabetic cema. Case% not in coma, but bordering on It, gave no evidence of kidney change ercopt pooribly hyporfunctibn. The fats1 camme), however, were accompanied by rigas of marked renal lnsufflolonap. ' Chmicrl Laborstorz: The rtudios concerning aoldooir Which have been carried on by Dr. Van Slyke and the men working ilth him, ami *&Ich have been referred to in prevloas repcrte, hava furiliehed ba8lr for an`extenilva report, oa- cup@ng 165 pei&a'of the'Joumia1 of Biological Chemietry, under the follow- i&itler: " `j .,i: * :; L,:: /=,"..*i, ;.`J *;.*: .1 `..' ,!`, ,+:"f?fff'"** ,`t,-1. Z. , ~`, ' The Bi:&b~nat e ~Cdniiintir&fio~~ df &he'Blood" Plieu& :`lt i" `? Significance, and it8 Determination as & lfearur@ of ACidQ~i# . rl Dr. Van Blyko and Dr. Cullon. . A Method for the Detennirrstion of Carbon DioxidC and Carbonates In SoLuti on. Dr. Van Slyke. The Electrometric !Pltre4tlon of Plaeuias i Mearure of Its Alkallno Berorve , Dr. Cullon. Tine RelatIonship Betwoan Allcsllnj Rsserva and Acid Excratlon. Dr. Flta and Dr. Van Slyke. Alveolar Carbon Dioxide and Plaarns Bicarbonate In Nor~~4 Man Dux?nt; Dlgastlva Best and Activity. Dr. Vsn Slyke, Dr. Edgar Stillman ad Dr. Cullan. Paa Elood, Urine and Alveolar Air In Diabstlc Acldorlr. Dr. Edgar Stillman, Dr. Van Slyko, Dr. Cullsn and Dr. Fltz. These studies bring evidence In favor of the Vibiv that acidosis mxma a de- pletion of the al'kalina rea3rve of tno body. This alkaline ro8arve conslets of the blood bicarbonate, In that it raprssante the base avallabla for the neutrslization of mora acide. The method devised by Van Slyko for the esti- mation of the ablllt; of the ylas;me to cornbind with carbon dioxide under definite tension, from which the blcarbomts content can be calculated, thorafore offers the beet method for estimating the degree of acidosir pres- ent . Thlr method 18 ertrmely 81mpl8 and ha9 slroady co~no into wIda u8o and will in the fit&e probably provs to be one of the 8tandard clinical labora- tory method8. Dr. Van Slyka ha8 ml80 developed a new, rlmplo and amurate method for the rapid detemlnatlon of oxygen in the blood, which has been employed by Dr. Lundage In the etudloe concerning rate of blood flow prw Iaarly mentioned. Indldltion, Dr. Van Slyke and Dr. Fits have devised . `. ,.- new method8 for the quantitative determination of hydroxybut@c and dla-,,,, * , `a , .' ..* I I( .,. ,. .,i." cetic acldr fa the blood aad &IN, and the method hae been anploysd by! is~x : ,`. * ,: * c . .