REPORT OF THE DIRXTOR . OF THE XSPITAL. saxluary 1915. 3V.L.i;;; t?ie last yL..artt:- :*a.l.:- ;:%ie::ts C.V.ifeYiiis f:+C;.. Ci;3 Or` tha fcllof;ing 3: . &a . . . C.lb 3s :i:--d `. ;s;l 22.i'ite& to tile Ilospitzl for trear,ant 22-d S-tLi;-; xm.:;e 1oSzr ~ne~;c;:ic., .li?.`ce",as, an2 heart disease. A few of the patients foz:erly under treat- mr!t fc: bv-= ,+ilis of t!le cectral nervous systen have been readmitted for short periods to raceire additional treatLent. I Amfa Lobar hieuizonia: The work on acute lo'car pneumonia has beor, mainly a cant i2mtion of that carried on during the past uears, especially along the lines discassad ir. ow bast report. The rxrmber of patients adLlitted furing the present quarter is ajoLt k-ice as large ae the r,mber admitted last year during the same period of firm, so it seems probablg that quite a large number of patier,ts wili be available for study durirg the preser.t year. Unfortunately, so far as testing the value of the mthod of treatment by t;ezle of ij-.zur,e SCI-LK i-s concerned@ very fern cases of Type I. have beer. admitted. On the other hand, an unusually large proporticln gf the patients so far aduitted have been infected nith pneutxococci of Type II, Fur- thea. experiance yrith the serm treatnent of cases of Type 11 indicatss that ths value of this method of trsztkent ii1 tkesa cases is not nearly so great as it is in the cases of Type I. This ms to be expected from the experimental studies. Further efforts are being nade to deternine whether or not sor:e uodification in the nethod can be made Thick xi'1 iiy!,rovo the results in this type of cases. The results of serum treatment il? cases clue to Typo I, however, continue to be very encouraging, and there seems svery ~'a2802 for believing that s3mti tresrment in cases 6~s to this type of organisx I is of veq Great value, ?hon one r~~az;l~erS that the n%i2er of deaths in New York, tile IO ;XlX~Oi'iia caused by pneu;-.lo;oc;l of Type I is Lreater t:_all t!;e deaths due to di;ktheria, and muc11 greater than tl-ia total xxf;er of ieaths ilv.e to scarlet fever, cerebra-spinal fever, and typhloid f3ver 2o~l;>imad . d 6. L, it is i;ite evident that we are I , : : , -$- I justified in considering thi I type of pneumonia as an entity, and in feeling zmch encouraged if the mbthnd employed is able to materially reduce the mortality in cases of this one typo. It is planned during the cnming winter to supply a limited XGXt cf sel-uiz to sevaral other hOSpit8lS, so that it is believed that by sijring ;;c i.2ll obtain Sufficient Statistics to pe;rtit of a definite judgement as to the therapeutic value of this serum. During tho present quarter the studies of Dr Dochez and Dr Avery concerning aptidomiology have been extended, and the observations previously reported have been ccnf iItled. The report of this study is no.-{ in press. Dr Avery's study rf the dis- 2ijution oi the tie substances in the various fractions of the protein of the -eru;;i have also been extended and completed, and the report will appear in the Feb- runry nxioer of the Journal of tlturiaxxx&& Experimental Medicine. The studies ~2~6 Sho:m tilat practically all the iL-.~une substances are contained in the fraction of protein precipitated by 38 to 40s ammonium sulphate. Since this precipitate con- tains only one sixth of the protein, it is evident that a method has been found for reLcving a considerable amount of the protein of the serum used in treatment. This is no';l being carried out on a larger scale, so that treatment `may be made with such zcncantrated serum. This work also has considerable pusely scientific interest in relation to the distribution of tiune bodies in the 1 rum protein fractions. Q , Owing to the fact that Dr Dochez, as resident, has been compelled to give a considerable amount of his time to the care of patients, he has had less opportunity than Previously to carry on experimental studies. However, he has continued his study of the nature of tile immnity in Pnmmococcus ir~lcos~s infections, and it is to this ;;r031~ that his experklental work roil1 be largely devoted during the coning winter. Eie kCooratory studies o f t:?e r\,irector cf tLe Hospital have been aatil~ ovctecl to a e2.l; of mthods of qAclvl A-Ay 2rokcinz activa ixmnity and to a detemi- ..::tioC of t& 3est ;I;etIlod `oy ahich such rapid active imzunity may be obatinad. It P c 3 :: - - k.lS Sac2 four-d that if even the slig:ltost graze of ?.ctlve immunity is produced, the ".ii&C;' of LiilLie S,!XW:, in such ai:knl, is Lnor..O*~sl; inCrcas3d. 17ith the methods SC frtY t,St?d, ho..v3r, it 113s be3n L;poscii;l3 to ErOd-~ce t;v3n tilisslight graG.3 of 23tivo irl;rdr,it;- infibe of ;t period of six days. It is hopod thnt i: zthod x;- be :,-.-i;cd for d;cr;asing thi3 porio;, in order that ~.;`e ~27 h5vd expel*imcnt21 justification ior Co:..`Jlnir.; vaccination ::itL passive: ii:~:.ur,itatior in our pati.eShed, alcohol-precipit ated ani g:ouiid pnemococci, is apparently 35 protect ise agains': p~euz~ococcus ir,faction in mice and rabbits as an aliquot amount I of -i;hc o:*it;inal serz. T!:is preci2itat.e r;ay furt.;ler be waAe;l in saline and still retain its CUl3tiV6 pl"3p6rti33, ar,d in som imtmces, -Aen freshly produced and dis- 301'13d b]' a S:zli amount of alkali(iIaCi!) will sti$l retain as mch curative value as tha o:`iginaI serx: fro- which it is do:-ivsd. The addition of tco grer,t mount of al- `2. .' ..k -A, evea ii it be subsequently noutralirod vlith HCl, may destroy the curative value. T:ie c;LLie efiect, ho\:`ever, is also rpoduced by the addition of large amounts of alkali to 310 originnl diluted serum. This curative precipitate contains a ver; %x&l amount of pxteins as dstorzimd from the tot:1 nitrogen. mereas the origiml 6erum con- tnins 6 to 8: of protein, various speci;.;ens of the specific precipitate, restored to th origiml volum of &term, have been found to contain from .18 to ,345. From the ob- sorvations hitherto LBde, it would seen that the strength of the protection afforded 2: this pr3ci7itate io not Froportionafo to the percentage of protein present. The concsntration of the precipitate in smaller volume apparently render-e it possible to protect mice against soner.%at larger doses of the pneumococcua than can be :rotccted again st by the whQle 30ruu. The serum from which the precipitate has been rxoved contains much less protective value than the original serum, although it USU- ally contains a perceptible amount. The method for producing the maximum amount of pre.* cipihate, the possibility of putting this precipitate into solution without destroying its protective value, and many other problems remain to be worked out in more detail. YJe do net know, for instance, whether the precipitate itself is the protecting substance or sone other combination of antibody adherent to it. It seems evident that the pre- cipitate does not protect in some mechanical way, owing to the fact that it may protect equally well when dissolved,and also owing to the fact that the undissolved precipitate does not protect against a type of pneunococcus other than the one against which the s0nu.2 eqloyed is active. It rrouid seem that there observations open a field of considerable interest for inns s t igat ing the satwe of immce bodies of various sorts, and indicate a rneansl of con- zeidratbig iZfWne -2OdiaS il-4 a SOh-tiGL irk treatmfik, tot 0Cy cf priemo:&, &I, of 10:;; protein coii*uent ?:Jhici? .tzay be advantageously yosslbl;- also r;I' otLer icfecticns. Dsc. 14tk. - .i . DllutEt2 ser-d2 0.1 + Culture heumcoccuo I 9ai 3.05cc Survived ? . . . n II 0 .Q?S n 2' n n 0.025 n 4, n n 0.0125 n 5. n n 0.00625 + -- 14 ---- day6 -- --- ---- 6. - ---. Dlnoclvcd precfait;7.t3 0.: f n n n n II Survived 74 n n O.G5 fl 8. n II 0.025 n a ?? o * n 0.0125 n 10, n n o.co625 e 11. Exhausted Serum 0.1 n 12, II II 0.05. + 13. 366 II 11 0,025 + 36O lict Contra1 + 0.05 + 200 15. n + 0.0001 + 16. 180 " + 0.00001 + 4o" 17. n + 0.000001 + 48O t \ .- ~'ti -\- . . , Diabetes: During the past quarter tha efforts of Dr Allen and Dr Stillman have been mainly directed to tha treatment of patients suffering frca diabetes, along the lines discussed by Dr Allen in his report to the Doard,last April, It nil1 be re- ~~11~4 that tile studies on animals suffering fro m experimental diabetes led Dr Allen to believs that for the successful treatment of diabetes it would be important to keep th2 ;:.t.ier,t on as loci ?IS caloric diet as possible, in the hope that the demand then r;scie upon tha assinilativa functions of the body would be reduced as far as possible, the thaory being that any increased demand made on these functionc, over that absclubely t-*ecess~,r;- for t3e supply of suff5cier.t enorg; to carry on the activities actually necessary for life, would cause a strain on thq organs functioning in assimilation, in- cluding the paIlcrea8, and SO reduce the functional power of such organs. It will be re- . called that Dr Allen showed that if two dog8 be each rendared diabetic 6a the Sax?10 grade, and that if one be fed on a high caloric diet, and the other on a low caloric iict, the one receiving the high diet would, in spite of this, lose weight, and would also become feeble, and finally die. The other one would al80 lose weight, but rsmin n?;mently active and in a comparatively normal state. Twenty seven patients have now been admitted to the Hospital, suffering from diabetes. Sixteen are still in the Hospital. The study of these patiects ha8 shown that, by the withdrawal of all food except alcohol, all patients suffering from diabetes can rapidly and completely be relieved of glycosuria. It is also of very great impor- tance that, at the same time, the excretion of the abnormal fatty acids is also reduced to a minimum, 80 that, instead of the withdrawal of food causing an intensification of acidosis, it is the best mean8 of relieving the patients from threatened acid intoxi- cat ion. In order to obtain this freedom from glycosuria and acidosis, it is sometimes necessary to withhold food from the patients for a considerable length of time, in cer- tain case8 as long as eight days. After the patient is free of glycosuria and acidosis it is then necessary to get him back to a living diet, containing a sufficient amount of the o-ariit?s kind8 of food. No effort is made to have the patient increase in weight ,5(b - a 1 . . I \ iioxever e If he is emaciated, however, it is thought important that the weight should rarzin stationary. By carrying out these simple measures, it has beon possible in a lmge number of the cases, to keep them free from glycosuria and acidosis and on a caloric diet of sufficient size to maintain life. It will be remembered that in his previous rapnrt Dr Allen stated that he thought t!lat by this uethod, the total metabolism night be reduced. To test this hyl;othesis n series of calorimeter cxperir.lents have been carried on with Dr tusk and Dr De Bois, ti:c pntients being temporarily ret;ovcJ to the Bollcvue Hospital for this purpose. This study is still in process, but in one cast, at least, a reduction of 205 in the basal . .ctzbolisc ?..a$ been observed, follouin,; treatr.:ent as outlined. Ilost of the patients llli'e sho*;:n ir.creased tolerance to carbohydrates and protein follol::ing the procedures .iGccribed, though it Is still irlpossible to say whether it is essentially greater than that cbmrved nhen patients with diabetes are made free of glycosuria and acddosis by th_) sloY;er methods previously empJoyod. It must be rerler:berod,however, that with the :.-thods previously used it has been impossible in r:eny cases to render them free of -1ycosuria and acidosis. Only further extended studos can show how great prolongation cf life nay be expected by the method employed, as compared with that obtained by ether :.:ethods. It is generallt assumed, however, by clinicians that in the treatment of dia- betes it is of great importance to render patients free of glycosuria and acidosis,and that thereby tolerance may be increased and life prolonged. It seems that the m&hod ,?coposed offers an improved way of doing this. That the total caloric value of the diet is of importance, and not merely the actual amount of glucose-producing sugars and proteins, bs shown by the fact, now well established by these studiss, that where a patient is free of glycosuria and acidosis on a given diet, containing proteins and f?&ts, with of without carbohydrates, the addition of a given amount of pur fat, without any change whatever in the amount of protein and carbohydrate, nay cause such a patient tc -;nin become glycosuric. This fact together with the fact that pipaemia so Often `3c3curs in diabetes, has suggested the importance of further study of the fat metabolism ir. diabetes, especially a study of the fat content of the blood. Consequently it is - - - \ f ::: ,j r :Lxxed that durlcg the coming quarter Dr IIclean and Dr Stillman will carry out furthor studies dealiz;; with glycaemia and >ipaemia. Dr Allen is also engaged in the study of the pathobogicsl material obtained from experimental animals and cases of human dia- betes to study further, by means of more delicate stain ir. tLe ;onncraas occurring in diabetes. , Sieart Disease:- Studies concerning the mode of cor.tinuod by Dr Cohn vliththe assistant of Dr Jamieson. the action of digitalis in patients with nomal cardiac blcod pressure xithin normal nrc bein made of the action ir. patients in which oedema, lir.:lts, are nor in press. reactions, the finer changes action of digitalis have been The studies made last year of rhythm nihhout oedema, and with During the present year Studies of digitalis in patients with abnormal cardiac rhythm,and and abnormally high blood pressure are present. Special Studies are being made of the mode of action of digitalis in patient6 with fever,especi.- 4ly in cases of pr.eunonia. In previous studies,in order to determine that digitalis was actually active in ?r. individual, it ha6 been necessary to push the administration to the point of alter- in: the heart's rhythm(heart blcok)or of inducing gastro-intestinal symptoms. These wer~~ the cost certain te6t6. In reviewing the electrocardiograms made during these studie6 it has been found frequently almost uniformly - that before these signs became manifest the shape of the so-called T wave in t:>e electrocardiogram became altered. With greater attention to the details of calibrating the curves, it has been found that the beginning of this change can be detected easily - in two to three days - after giving the drug. This chage,together with a change in conduction between auricle6 and ventricles,which also.often occur6 early,offers two new,sure criteria for deciding early that digitalis is acting on the heart. By observing these signs,patients may be saved from the dis- agreeable effect6 of this fom of treatment. In a single instance abnormal primary negative T wavea have been seen to become less negative, and later positive, These changes persist varying lengths of time, and the curve6 return to their initial form after about ten to fourteen days after stopping the digitalis. Tests of these signs in patients with fever(pnsumonia patients) have been nade. \ b.3 4 - . - * 1 4 (. 'Ihe faih.z of digitalis in these circuzx+tznces to lower hsart rate is fmiliar, and it6 u6e by wnp peraons haa been di&xntinued. In xany 66 thew Fatiants the elect--o- c:rdiogx~Lic charges z?rez:-- : entice, :.lsc ccc: r r.ftcr the a;l,:inistrxtion of digiteli" pi`oi;ally 2fte;- t:?e S3za l,r.4!1 of tir:e, r.r.2 ::it;; the sxil:e iosa&e, 2s in casas of czk-iiz,c diva 2.f;d. If f::rtl;er ~::;z~-ic~ce SC-X cc-i t::esa obsa;-vnticcs, -.ic skll hara vf.lu2.ble na*:. sethods oi judging 'tke value of c6t-t2in stii.u.1ant.s in Case conditions. It h3.6 previously been 6upFosed tk? for di&itz.lis$re~:~?ticn to be ef fecient i:; 22335 ::,i+v:l fa-le- . ;.:ore thm the usucl Jose ::aS req:irod. Dr J.z:ieson 1x6 therefore cc:.:;;zrdd t::e latk2.L iksa cf c-ystallins Strc;il:Ilti:in ir. xcz-,:?l czt; ar.d in c2tS t;rit:i 3::;erimnttl ~~8~..5:'+2, ir.Gccai by ir.;:ffl:tion. He k.6 fcucd t;:-t in bct.11 series of ?.T.ixlS &at:1 tcct~r3 after tk s?za z-.~cnt of t::e LiYs 11-s been injected;that tk3re iS nc differarce In the z.c',ior, G stro;ahthin in the ihfectsd 2nd ih the son-infected ?A- riS. . . This result barxllols +,>e ojsarvations x.do in -,?:I;ionts. IIoaever,:Aiie the in- fact6.i cats 6:Acxed zall-* ..xl:ed consolidation of the lL:ngo,they fzilcd to develo? fever- It is ~osaibla that the absence of fevar fr.,iicates that a true intcxicatios,interfering *::iti: the actior. Ot digit21:6,-ifaS a'3sent ,nnd tha';,had iever been Frcsant,tha result ::ocld iare been different. It is planned,thercforc,to re;eaf tkese e::;oAklents in dogs. I&mm heart6 in which electrocardiogram have sxrplied evihnce that the sriallor 'crazches of the auriculo-ventricular conduction systec had undergono pathological changes (bundle-brazxh lesions) have been studied in serial sec'iions. Structural alteraticns mre found,but it was ixxpossible to say definitely r,hether these x-o to be correlated Tritk the alterations in the electrocar&iograi:s. The hearts nere sx;plied 5y Dr Tho';346 Lmis in a state of dissection designee fcr wigking the czvities scparately,and were nc;t TAta fitted for the Itrrpose of ths Xstological stcdy Secauso the continuity of tke endoc2rdkm had been scrificed. Tl;a t;".ilm-s to find an adequate lesion to zccomt for the c!xz~;e 2.7 lia in this cir2~*ust?3ce. vrt;lez e:r?eri;:lents on t:ia dip+, =4.i;-~tion of tka vzgus nerves and nore es:eci6lly Ci tile 2.CCG13iTdtOr n:rveS Era in progress. It ;ES ba6n found that t:ze sinus node doss 7,. ,~,' ,,, I.--_ -k- ilct for?.: a reiay in t;i~ path of th3 vagus nQ:`vcs. The ncv; oxpcrimnts are based on the i;;a th2t An-5.35 left yaps st~ul~t~on, th2 azc2lcrator wrvcs csI,sclally am rcspon- Sib13 for 2o;:finu;3 auricul.ar activity. a Chcri.ical Lsioratory:- Thz foil:voing is a report of tlio nork carried OT: by 2: `.i^:; y]v::c . . 2r.i t>*;: pkysici:ns r:orl:ing under his irzcdiato direction. i?;:. s;i' 1;. or' t;;s iat' 0 f t;1o prokcts of protein dig;stion,bct;un t-::c years a&o .:it:. ijr ::-,ys:- , a:;J ir,t ,rruptcd last ycrrr in ordor to dcvclop rcliabl:, mthods for urea Jit,r...ir.ation in blood a3d tissue oxtracts, his beon taken up agairi. i!r Cull>z azd Dr !Ick:an havti invcsti?ntcd the question of urea formation in the liv:r ir. Cti;t:yi;dd Jc;s. Perfusion of excised livers by tho Folin schoqi failr;d to ~cv:al an ability on the part of this organ to transfom acino acids into urea, and has :hrorm doubt or. the fomcr vim that the liwr is the chief seat of urea formation. "0rkir.g nith liv53 aaiziiils at vary i-7 ..b psriodc aitor mat fcodingr$ovover, it has been found that ;i;c `nepatic blood in cvcry case contains urea in groatcr concentrstioa tha- th3 portal,t':ie iccroase in the urm rosulting fron passage of the blood through :he 1i.m-z vzrymy, in diffr:rent oxpcrimnts froLl 3 to 15 $ Passage of the blood through the IXSCIY C;?USOS relatively siizht increnae,ususlly none, Mr Eajling of Dr Carrel's departnent, is experirienting with portal vein fi.stuLS in Zc.;s. Then the exporimnts are successful, as procises soon to be the case, it nili be pcssible to follow the tize cunro of the rise of amino acids in the portal blood hftbr the ingestion of protein; by determining at the sam tim the curve of the blood urea, the two curves nay be related to the progress of the food proteins along the alimentary I , I canal, as show by X-rays. It vi11 be of interest to ascertain how soon after the in- gestion of proteins it is possible to detect the presence of their products in the blood , / an2 how soon after this the fomation of urea begins. It is also of theoretical interest to ascertain whether the body begins to brwk absorbed amino acids into urea as soon as their absorptior? is under vay,omhether it waits until the tissues in general have be- co::;o charged with zino acids in OXCOSS. T?ith 12 rjdling it is also planned to cxperti.lent with dogs having thoracic duct 2 .&w & f istulas, in order to deterr.line horv important a chnnnol the lymph is for protein ab- sorption. Mr Cullen has assisted Dr Avery in studying the effect of irmunizing horses -5 - -ainst ~trrvp pneunonocci on the relative propostions of the different proteins in the blood. It is of interest to determine wether the protein fraction containing the i:.sune bodies increases during ixmnization, and whether such increase in any way Para- llels the protective power of the sex-m. :*:ith Dr of urea Dr lIcLean is making a study of kidney function in diabet3s,and, in conjunction Cohn's dtipartmect, in heart insufficiency. The ratios of the concentrations and chlorides in the blood to the rates at which these substance6 are elininated by the kidney has been nathematically expressed in equations by Acbard,and Dr IdcLean~s studies indicate that these ratios are very delicate indicators of the excretory power of the kidney. The effect on these ratios of the adr.linistration of digitalis to cdecatous heart patients is striking, and it is hoped that a comparison of the results of this study with electrocardiograms may decide the question as to whether the primary sffect of digitalis in such cases is on the heart 01) the kidney. Some of the diabetics show a pecSiar,abnormally increased permeability of the kdineys to chlorides,the significance of which is still uncertain. This condition is also being `studied. In order that sufficiently nmerous data on the blood chloride6 night be ob- tained in the above work it was found necessary to devise a nethod which would pep nit accurate determinations with mch less material than the 2Oc.c. required for the usual Volhard tit rat ion. Dr Van Slyke and Dr McLean have devised an iddonetric aethod wb.kch permits the determination of the chlorides in ace or two cat. of serum with m error of less than 1 part per hundsad.' The study of the chenical constituti&(anfno acid content) of certain food proteins, begun by Miss Vinomad last spring in conjunction with Dr Osborne of New Haven is being contimed. / A- \ bliss Vinograd with the collabcratioz of Dr Losee of the Lying In Hospital is 2r.taCed in a thorough study of the Abderilalden serum reaction, using the Van Slyke ?.r:ino nitrogen :-.:ethod in order to obtain a gunr,titc?tive masure of the extent of pro- tiolysis occurrir.~. Tha technique has been so developed that an active serur.1 usually -.iv?c aT: ircrease of 1005 or nore in arlino nitrogen; so that there is no longer doubt ?P ..J to dither the occurrence, or the dc;ree,of proteolysis occurring under the conditions ci the reaction. It does not appear that the reaction is very specific; but a final decision ::.3 tc its value has not yet been reached. Recently stiwral European writers have announced that in the roost dangerous tyrus of diabetes the orSar,isn loses not only its ability to burn sugar, but also its -.:ildty to mtabolizo the alimentary ar-:ino acids. In consequence an abnormally large ,;rc,;ortion of the, uricary nitrogen is in the fom of mlino acids. The datemination of z..ino acids in diabetic urine is subject to poculiar pitfalls, and it appears un- certain that ar.y of the clinicians reporting the above result& have been aLiars of them. It is planned therefore to take advantage of the diabetic naterial in the Hospital to obtain data on this ir!portant point. R.I. Cole .\ I