Tobacco Documents Online

coroniry hln,rtl flow in the huntan hr.rrt, withuut rny traunratic prrtcedures T1iis rncthud mjy now t.c jprhcjhlc to imprttvcd assessment of coronary attcry cundttit.ns in /stTulatitN+s suhlcttcll to pn+spcclrvc stutly in rcl.tnm to environmental (actors Eilsewhere, the tole of blt>,xl sugar in regulating non cstcrified fatly acids in the serum has been clucidaled, and glucose kuding shown tu inhibit btnh the increase in Irce lalty scids and the increase in cardiac stroke vulunse that may be induced by nicotine or smoking under fastinR conditions. In ancxhcr IalxKatory the biochemistry of artcrioscleroric changes is under investigatiun with emphasis on the rok of arterial acid rnucr+(w)lysac- chsritks. An effect ts( nicotine in inhibiting the Irpid-clearing activity of hcpsrin has been rrbservcd ('crehral bkxxf flow has been measured by a phr+t<,graphic tcchniyue h>tlowing retrograde injeclitxs nf a cr+ntrast medium intu the brachiul arrcry (lgarctte smr+ktnR was found tu incicase flow in the tcrcbral aeterics 'Thrs effect is anrrhutrd t,+ thc carM+n rhuurk tnntcnl tu/ the smtrkc since it was duplicated by inhaktl (Y/, hw nrA prrrlutcd by nicrrline injcctit+ns lhrs study call, altl'n1Nrn t/+ tTx• {a+.uhle pharmacnlagical and physio- logical srRrr+ficancc t+t carM+n drt+srtlc in sonic effects produced by smoking Nuntcrt+us tNhcr UIt1/1.Yra~(UIJI +nvcsttgasi++n< havc been puhhshrd by vanr+us ( truncil Rrant rrt r(acnt. ilurinR the year jusl cntkd In the present cuntc.t they will not hr revttwcd in dtt.ul, but a11 arc li.ted and abstracted clscwhcre tn this tletwxt C ion.ctrtutioirul /•(rctnra vrt(l Smr7Ai,'t~,r Earlicr rc(xxts have referred to the rrlatiuns drscr+vcred between body build and smnkinR practices 7ltcse must havc S gcnctic basis f'rnjcctcd studies will attempt tu tk,crminc whether there arc parallcl relations between btxdy build and susceptibility to certain diseases 'T he studies showinR rcla- Iivcly close resrmhlance in snsoking rracliccs of itkntical twins as compared to fraternal twins ( nul (•ouncil-vptrnsnrcd ) have often been cited Thcse also reflect a genetic basis A current Council research prajcct has shown yuite siRnificant tliflcr- enccs in types of occupation selected by smrtkcrs as cumpared tn non- sn+okcrs, as well as f.etwcen thtr.c sclrctrd by cig.+rcttc, ciKar and py+c snu+kers Mnreuvcr, crrnsislcnl gratlyd solurnccs r+l arranRcrnrnls nl r+ccu paln+nal frcyurncirs arc ctnrrl.ttctl with rlrrrres r./ tttb,ttc+. ct+ntuml+w+n It is rcaturuhlr Itr tuncludc 111.11 snnrkrnR twhavit+r r. .rss+q r.rlrtt with t+crv-n atity, anrt Rrnrnt rnrl.hratir+rns may he I+tr.enl Srvrr.tl ncw .Ir~~trtt h.tvr a.t++t+I+uyly I-t't'n %t.ut+•d tn I-A (turthrr utlu .,n,l I+lnni~.il~lt .~. /Ur.~turct) .rt thc psychoingical level hy several diBcrcnt methods These may lay Ihc lounda- liuns (or later studies of personality as related to disease su.ceplrMltty Carcirnogenesis Studies Approaches to the investigation o( cancer have also been oriented on the basis of the three hy(x)fhcscs that have served in this report for classi6• cat.on of varitsus invcsliRatiuns into the etiulogy of uker and cardiovascular disease. The ('ouncil's ty61-64 Annual Report contains a dctaikd review of sptxtsored cancer sludics, particularly Ihtne crxrccrned with the bioassay of cigarette smukc. This previous report concludcs: "Tlte overall impression gained from these many bioassay studies is that (Uhacco smuke is inaclive or of etlrl•mely minute activity in Ihesc several artificial systcros, none trt which o( course actually measures human respunse untkt rcatislic conditions ibt results tend little to support the hyfxNhcsis that ciKarclle smuke can act as a direct conlact carcinogen in the human lung " 7ltese bioassay studies have been undertaken in order lu test the first hypothesis regarding reported association between lung cancer and tobacco use. It is recognircd, however that numerous factors, intrinsic as wcll as estrinsic, play a role in Ihc pathagcnrsis of canccrs of Ihc several sites. fieuer understanding tsf the relative tole of such factors, whether from the realm of cellular biology or (rom empirical ubservalion, may well bring atxwt more cllective prcvcntive measures in the foreseeable future. Such measures are likcly to ht multipk, and operable upon several diffcrent kvcls I (;anrrr oJ the ()rol (:as+ity Clinical cspcricncc and epidemirsltsgical observations have amply dcm- txnlratcd the asstxiation of liver damage with cancer of the otal cavity. ('truncil sponsored studies have investigated the effect of induced liver damage in mice upon their response to benzpyrcnc applied to the buccat n+uct+sa ( ivcr damage was produced by administratiun af catlwn tcha• chlnride with or wilht,ut alcohol Squamous cell carcinumas frnm bcn>•pyrrne painung rkvrhqxd eatlrest in mice with liver damage int4ucrd hy h++th carht+n Irlr,rchlurnk •nd alcuhnl, and afw+ul Iwo mr.ntlts later m Ihrrsr trt•atcrI wnh rnhcr rd thcse aprnts rltmr, and two nutnths .trll later and at a rnuth (nwer Icvcl I/, Ih1.1r trcall'd wilh nenhcr u/ Ihr Iwu liver lu.m. 1'arallcl gnrut+% in whith cil;:rreltc smr+ke er+ndensalea were altlrhetl tu Ihc huccal cavrly drvch+l+t-tl n++ tunu+rs 19

lhctc c.pcriments are currenlly hcing repeated with anirnels in which liver d.rnugc is induced by dietary ckficiency alnne, without tnsic aRenls, a srtualinn that may concslxsnd more chtscly 1o curnmc*n human csrcrience. PnssrhIc mcasures for prntecunn of the liver are also untkr investigation I: .rt'rnnrcnts with smnkc ctmdcnsalcs are being repeated with higher dosages. lhe ruk nf liver d:unaRe in the reslxmu of Mhcr nrRans to chrmical carcinrr- gcns is alsu to be investigated according to plans under development .Cturfira with f:rrm-Frrr Alicr The ('uuncil has sptmsnred a scrics of carcinogenesis studres with rrxlcnts whith arc not rsnly free frnm bacteria hut alsu front all tornmsm known viruses Subcutancc+us inoculation rd strrric 1 nscthylchrrlanthrcnc in nil was frrlHswcd by drvchopnscnl uf hKalifcd ncuplatms m Iwrr strains rr( Rcrndree rats and in fuur strarns of Rcrmhcc mrcc lhe trlx•s. locations aml lalcnl perKxls were snnJer tu those snduced by the sante agent in conventional control aninials It thus aprcarrd Iha/ bacteria played no role in this instance of clxnucal cartunnRenesrs anrl no funttUt+n of the cttmmun known viruses was observed A rrrle by s.rnse rx cult virus cannot be comptetely ruled out if dclrcurrn of suth thrruld trr IKyrmrl the scnsrtrvrty uf present detection tyslrnss In trthrr ctl•rrrrnrnt. Iynrlth.urt Irukcrnu w.r% rltcitcd hy whrrlchrxly X irr,rth.rlrnn rn Krrmtrtc nn.i rd \wr.. Wrhtt,r, ( 11I enrl ( t]I11 srrarns whcress it did nrrl rrcur in nrrn ur.rdr.rrcJ trrnur,lh Sinte cylrydasntic viral incluvrrrts cuuld hr dctcttcd hy clcr Irrm nritrrruut+y in crlls frrrrn the cn- brgcd Ihymus Klanrls, it was crmslwltJ that an rxcult IcukcmrrRrnic agent crrulJ hc Ir.rntnrrltcd ro sutccssrvc gt-nrr:rhuns by vcrUCal Irjts:ry,c thrrHrgh the ovum nr pl.ccnla 'Ihe rclcvancc of these studics tu tmtkrstrnding of the rclatirtnships between viral agents, radrannn antJ thcruical :rKcnts in earcintrgcnesrs is manifest ('irrrs tihrrlir•a InvcstiRnlirtns cnnlinuc tn rrhtcrvc thc hi.lr J:rlhrdugic~l c(Irtts rd cig- v,rnnrn rcttc srtnrkc mh,rlaurrn rin the Irml;% rd ntitr. Iw-rh alrrnc and with )trrtrcalrrrcnts rrf thr IunR, at wrrh vrr.rl ,r/-yrrlt ut thr• farM/uUu.n ril url.uc Inrns SJrctral rllurts arr Ja'rnR rn,rrlc i., .rlljtn Iw'r,rr yu.rnlnaUrrn rrl .rrrnsrrl rnhatAuun f.y rtrvrl,rtrmcnl of hrrKhrrna.) •nd I hyurrluKaal nrcth.rrls td tr vr c.nnr.rrmR rtlt,uvr twnaRe 0 Ir rN etlx'trcJ Ih,rr ncc Irrrrgurm rtf rnhal.rliun 0 ~ tturlrct wrll lie r.p.rnrkJ /urthcr as nir-rt' srqphr.Irt,rlcJ mclhrrds /rrr ctrn- 0 c a ~, 20 o r r trolling esposure are perfected, so that the effects of numerous possible vari- ables can he assessed in a systematic fashion. As a by-product of the work involving virus damage of the lun6s, es- planled kidney cells have been trealed with certain viruses in virro .nd Ihe morphological alterations observed. C. ultures containing altered cells are being transplanted back into host animals to observe their behavior. Observalions of the nuckolus as affected by carcinogens and other ageols have continued. Other reports related to carcinogenesis are abstracted elsewhere. Other Concer Studira The chromosomes of kukocytes cultured from cancer palienls, prin- cipally with lung carcinoma, have been studied for abnormalities t.cfore, during and after treatment by radiotherapy. Palterns of mcususis have been studied in  series of 5,RR5 cancer cases in Massachusctls. Melastasis to the lung occurred in 26% of all cases, most frequently from Icslis, breast or burse, but often also from other sites. 1 he persistent danger of confusing secondary tumors of Ihe lung with pri- mary lumors was illustrated by a substantial proportion of cases which showed misdiagnosis ors the original hospital repcsrL ('lassifscatinns of lung tumors into histological types was reported to be uf linrited value because of the prevalence of mised types and the fact that only the terminal phase of growth becomes available for analysis, with point of origin ubscure. 1'ulmonarr I'firsiology Two Council studies have begun investigation of the lung suriactant now recognired to he essential for regulation of surface tension in the alveoli. Effects of the absence or impairmenl•of surfaclant in various clinical disorders are being observed. 'Ibe site of origin of surfaclant and hitxhem- ical influences affecting production are under investisation. 1 he cnrrelatitm of ante rrsorlem lung function appraisals with patho- lugical findings in whole lung, posl-mortem. is being undcrt.rkcn rn a pro slwctive study Mure precise definition and diagnusst of chrnnic puhurm.rry diseases is the Rual uf scvcral clinical and palhuhrtiic'al studrrs /1rm'hemrr'al ,S'Irulrrs lThc isulrurrn and nlrnlnctatnnr rrf /xrlylrhtnals anJ rcl,rtrd suhtr.urrrs frrxn luhaccu and luh:rccu srnrrkc h.ss Ix•cn asrnimvd, wnh Iruhlrcauun nf reports during the ycrr 21

Thc lunR term systematic study of the mclah„hsm of nicotine in the maninialian bcxly, including man, has prtrcecdctl at a high level with pubti- catinn (I/ eight rcports 1 he general picturc rs unc of rapid tkgradatit.n of mcnrine into ntxr tutic mclafx)lilcs I nuum labeled intermediates have been used to tracc dispcnal rtwtes 1'hormnrfrlogy and 1'sychoharnrncrol(>t;r}• Systcmatic study of the mode of action of nicotine at various synapses has been continued Meanwhile increasing emphasis has been pl.ced upon the psychopharmacology of nicodine as mentioned clsewhcre in Ihu report. Dogs, monkeys, cats and man have been included in such studies in several ccnters. Specific actitrns on thc central ncrvous system have been described and (he eflects of Ihcse upon behavior are being srwght On September 11. 1964. a d.y-kx+g round tabk conference was held in lAe ('ount,l oRices for drscussion of 7Ar Dchavrtrrut t-flcrrs of Nicotine and Snsolint In addition to members of the staff and of the Scicntific Ad- visory Buard, (he ftslhrwing project directors and guests altcntkd. Barbara B Brown, Ph 1) ,('ahforniu C'olkge of Medicine E F f)omino, M 1) , The University of Michigan Medical Schotrl Paul S T.arutn, Ph 1) , Metlrcal Co11cRe of Virginia Edward W Pchkan, M 1) , Hoston llniversity School (if Mcdicinc Carl C Pfciflcr, M 1) , New lerscy Ncuro Psychiatric Institute Duane G Wcrvtl, Ph 1) , 1 hc Vnivcrsrty of Kansvs SchrNrl of Pharmacy Kcn ichi Yamamntn, 1 he llnivcruty nl Michigan Medical School Mr G F Ttx1d, 1 obacco Rcsearch ('ouncil, Iontk+n, England Clucs to the effects which seem pleasurable of beneficial to tobacco users appear most likely to he discovered within this ficld. In combination with studies of Ihe psychological kvcl, illumination of the needs which persons, particularly of cerlain typcs, seek to meet by snsoking may he at- tained in due coursc, with possiblc clucid.uun of the degree to which such needs are nsct by the practice. ,Smokirtbr arlrl I'ilanfin C Thc scicntific literarurc contarns scvcral rcfxals.urKctitinp, thal Irrhxto usr may thmim.lr thc effective supply of at. r'rbu at rt/ rn thr INNIy nr .n, rr:rsc thr rlcnunil fur Ilns vrUnun 1 hc mqpIrt.UrN~ ~d sur h rrlNrrls h thAl .rnnl~n~ nrtrht trrnlribulr I r t 'n.1rU rns mtturntrd hy •.r rnhr, rr r. l dcflt rrno y U 0 n Itrc ("nuntrl .INrrr acJ an rnyuuy rntrr aarNhrt atr.l rucuUnc rrldlurn 0 0 © ships on thrcc lcvcl. r ~ v. 22 o Animals capable of synthesizing their own ascorbic acid and others dependent on an eaosenous supply were both treated chronically with nico- tine, but no change in excretion or lissue content of the vitamin occurred in either. In vitro, a destructive effect of nicotine on ascorbic acid was observed, but this was found to be dependent on changes in p!t rather than upon prop- ertics inherent in the alkaloid. The effect was not considered likely to be of biologic consequence within the buffered systems of the body. Although chlorobutanol, which stimulates biosynthesis of ascorbic acid, protected mice significantly against toxic doses of nicotine, ascorbic acid administration did nW. Ftence the chlorobutanol eflect is not thought to be mediated through ascorbic acid. These studies did not sustain any claims that nicotine influences ascorhic acid availability or requirements of mammals. Summary As research gocs on, evidence accumulates bearing on different theories of possible action of tobacco in regard to various constitutional discaxs. Over the yean, however, evidence to support the thesis that cigarettes exercise a direct carcinogenic effect on man has not been furthcoming. 'l his has been a source of frustration to tlxne who hoped and hyputhesized that such action could he demonstrated and that one or more components of smoke might be identified as being particularly suspect, thereby creating an opp.xtunity to remove or to counteract such substances. Failure to confirm d'uect carcinogenic activity of smoke, despite estcn- sive research, has resulted in the extension and diversification of effort to in- clut'e other mcthtxfs of research and to evaluale other theories of ptnsibk activity. Whik support fnc direct carcinogenic activity has been lacking, evi- dence in support of the sts<alled constitutiunal theories of host teactiun to environmental challenges has been steadily growing by presentation of new data and by new experimental results. 1'he theory of constitutional diversity as the basis fur individual diffcr- cnccs in susceplibility and resistance to cnvirorsmcntal challenging agents involves grcal cttmplcmity and recognizes many obstacles tu srmplc unJ rapid analysis. Ihe hruhrRit.l .nJ thi4xhrmital 1rNrndsliun (ut suth inJrvrdoal drllrr ences is cstahlr.hrd at IcrtlluatUnn of the ovuro, by thc cnndrioasNm n/ thal cell wilh the slxrm 7 huusantts of individual hereditary chcnucat unrts called genes are cr+ntributcd by each of these cclls. This gencral prrwcsc is 23 N

commom to all kxms of animal and plant life in which sexual rTprcxluction e><ists, ('cxnpksity of the interaction of genes during subsryuent development of the individual and diffsculty in identifying them does not invalidate their importance even though it handicaps their analysis and manipulation This must he kept in mind because there are many who still mistakenly believe that unless the genetic basis of a situation is simpk, it cannot be considered of great importatsce. It is also well to remember that the esistence of a genetic influence has been established beyond any doubt by the isolation and perpetuation of many strains of laboratory mammals in which Ihe type. amounl, estenl, and lime of cancer incirkrwe is definite and predictabk and rrpealab(e In these animals genetic diflerences influence the manner and rate at which drflrrrnt organs and tissues age nd become abrrormal in function The brr.ad genetic factor has hccome ckarly evi,knt because one can manipulale the sekctivc process of inbrccdin6 In laboratory animals This, of course, is impractical in man. While we cannM manipulate human malerial, we can and should rec- o6nize that there is strong evidence that the vast number of different genetic backgrounds and types in man present a situation similar to that in other mammals in which individual resprmx to envirtxtmental challenges is, to a lar`e dcRree, and possibty to a most basic and imporlant eslcnt, determined by the genetic makeup of the individual It is also of interrst to note that the broad principle involved scrm. to apply not only'to resl+c.nse to chalknges tnward cancer hanutirrn hut al.n In those toward uker formation nd toward cardiovasculrr dysfunctirrn and disease. T7scre have been several separate studies in which comparisons between identical and non identical twins under similar and under difierent cnvirrrn- ments have been made and smoking habits, olher behavior Iraits, m<xbidity and mortality recorded All such studies have shown that The similarity in crxtstitutksnal reactioxt of identical Iwins is far greater than that between nun- isScnlical twins It shtwkl bc emphasized that in man the nature or degree rrf the process of transmitting by herality these various constitutional tyl.cs from one generation to another is not of prrnrary imlortancc 'Ihis ii im- pcxtant in animals where matinRs are planned and crrntrrdkd Ffut nrr rurc can, frrr a mtrment, believe that man will iunwrNrsly Idan Irr avrrrd mekruR The types of matinRs in which even the mrat serious rr( surh trmyrk. Rcnr•ta' factrxs may he involved And even if he drd srr (dan, hit rlunccs rrf crrntridGnR or eliminating individuals who present greater health rnks (by sr) drrinR) would still be nr•gliRihlc a a practiul mattcr U 0 0 0 nn the other hand, the recognilion of the unavoidable and universal esislence of diffcrent individual human genetic types and the search for criteria by which we can recognize among the population those individuals mosl likely to he a serious risk in the case of cancer, ulcer or cardiovascular disease is probably entirely practical. The recognition of the exis/ence of susceptibility and risk inside of our individual bodies is the mrnt eflcctivc and the nHnt hopeful way of being forewarned and forearmed in the application of preveotive medicine . i 25 24

Abstracts of Reports Fach rccipicnt of a grant in aiJ frnm The Crhrncil Fur Tobaccr, Re- scarch --II S A, is resl.onsrbk for the initial prescnlaur,n or publication of the results of his research at scientific meetings or in rl,Prnpriatc scicntrfic journab. Following are abstracts, Moved by the authors, of reSCarch rcpnrts acknowlcdtin6 support from lhe Council that have appeared in screntrfic journals since pubhcatirxs of the 1963-64 Rcport of the Scientific I)rrccttx. TAese abstracts have been grouped under the lulluwins headings: I Psycho-PhrsitAt~gical Studies, 11. Cardiovascular I)iscase, ItI. ('arcmo- Ecnesis Studres, IV. Other Cancer Studics, V Pulmonary Physiolog1 Studics, V1. ('hemistr Ir Biochemistry Studrcs, V11 Pharmaculr,gy Psycho Pharmacoingy 'Ludres, V111 Other Studies 1. I'ayclto-Phy,ioluRical Studies "TASTE THRFSNOl.F)S FOR BITTF?RNFSS ANF) CIGARETTE SMUKIN(: " Fly Arnokl R Kaplan and Edward V. Glanville, l.atxxatrny of Medical (ienetics, ClevclanJ F'sychiatrrc Institute; and Roland Frschcr, Research Division, 1)cpartmcnt of Psythratry and Ikpartment of I'hysio- H>gical Chcmrslry, Ohiu Slatc Ilnivrrsrty Mcdreal kh,r.d, ('ulunrhus, Ohru. Nature 202.1360. June 27. 1964 /(irrmtc Krhl.rnl T-his cummunicali„n rct,ads thc ..•-ruur,n I-Iwccn the srnr,krng hahits of 31 to S/) ycar old nulcs auJ I, nr.rli s. .,n,1 rh, rr taslc thresh,dAS (or two bitter-tastinR comlxrunds, yurmnc .rnJ 6 n la„I,yIrhnrur.rcrl (I'R(P). a phenyllhiourea com(xrunJ, taste scnsnuvrty lu whrth r% hum4l.rlly ,Ir,,rnb- utcd, consistent with the hypothesis of a snnplc Kcncuc Jrchotumy '1 he es(~crirncnls ctxrfirm a rclatiunship between smukmg :rnJ biltcr taste Ihres- holds. From a tolal of 266 subjects tcsted, only the 34 "heavy smokers" who used 20 or morc cigarettes daily and 40 mm-srnokers in Ihe samc age range were sckcted for comparative esamination The most significant Jillcrence in tsstc threshold for quinine was observed between the male smokers, with a mean threshold of 7.8, and the mak non smokers, with a mean Ihreshold of 4 6, a highly significant statistical Jrffcrcnce (P l/ IXII ). -1 he fcmale smokers were also kss sensitive to quinrne, but the drflcrence was lcss fiRnihcanl (P 0012). 'Taste unsitrvrty /nr I'ROP, like th:H /or yuinine, as luwcr in smnkcrs than in non snmkcrs in )Mdh nralcs (/' l/ l/lt ) and ~males ( P 0 (11)4 ) <i, OtA.r grenrer, Nati„nal Institutrs of Ilr.ltfh ( 2) u 0 m "A(i(i, SI:X, ANI) fnSll: SI:NSI I IVI I Y " 1)y Idw:rrJ V(il.,nvrllc, 0 0 B m m Ph),.nd Armdd R K.I'ten, 1'hl), 1)rl+rr,mcnt of Mcrhtal (icncthrs, I hve- c ?~ - a ,. s land Psychiatric Institute, Ohio, and Roland Fischer, PhD, Ohio State (lniversily Medical School, Columbus. lournaf of Grrconrufuty 19/4:474- 476,(ktober 1964 (Grantee: Kaplan) TTu c/fccts trf aging on taste sensitivity were determined in males and Femates between the a6es of 3 and 55. There was a gradual increase in sensitivity in both sexes up to the age of 16-20 years, followed by an exponential decline. Sensitivity to 6-n-propylthicwracil (PROP) and qui- ninc were similar in both seaes up to the age of 16-20 yars, but thcrealter male tasting sensitivitr decreased at the rale of 0 052 threshold per year For PROP and 0 066 lor quinirx, compared to declines of 0 026 and 0(N3 re clively among Femaks Females were more sensitive tasters of hydro- ic acid at all ages. OrJ<er grentors National Institutes of Flealth. "nIFFF ' RF:NT1Al, TASTi? St':NSITIVITIFS IN DUODfN/1l. AND (iASFRIC U1.('UR PAT'IE:NTS." By Arnold R. Kaplan, PhD. Edward V. Colanville, PhF), and Wilma Powell, Cleveland Psychiatric Institute, Ckve- land, Ohio; Roland Fischer, PhD, Research Division, Department of Psychi- atry and Department of Physiolcssical Cbemistry, Ohio Sta1e Univenity, Columbus; Mario Kamionk.owsti, MD, and Bertram Fkshler, MD. lkpart- ment of Medicine, Western Reserve University School of Medicine at Cicvc- land Metnqxslitan Cicnera111ospilal, Ohio. (:astrurnrtrolury 47/6: 604-609, December 1964. (Grantee: Kaplan) Genetic Factrxs predominate in determining taste sensitivity to 6-n- prnpyllhiouracil (PROP). They are less important for quinine, another bitlcr esmrpound, and appear to play a minimal role in tasle sensitivity to hydrochhaic acid, The distribution of taste thresholds For PROP is bi- modal compared with the morxxnodal or "Gaussian" curves obtained lot quinine and HC1. The possible rote of constitutional facton in ulcer was investigated by delcrminingg tasac sensitivity Fur PROP, quinine, and 11('1 in 121 subjects with duoJcnal and/or gastric ukcrs. SiRnificant diflcrerxes in tasle sensitivity for PROP were found between the 68 ducxlenal ulcer subjects and the 34 gastric ukcr subjects. Duodenal ulcer subjects were more sen- sitive tasters both by chi-square evaluatitm based on the assumption of a bimodal Jistribulicxt (P<.01) and by nnn-p~rametric tests which involve no assumptiuns as to distribulion (P<.001 ). Subjects having IrHh ukers resembled the duncknal uker group adhough the number of subjects ( 19) was Nro small to permit significant statistical conclusions. A volunteer group shuwcd I'RI )1' sensitivity similar to the Rastric ulcer suhicc,s Nu significant dillcrcnces were found Fsctween any of Ihc Rrrrups Fur either quinine nr IN') taac srnsitivily 'llusr dala +ulrlw,rt tlsr concept that gaslric and durwlcnal ulrrrs havr diRcyr~g consUwti~rnal baclrruunds and Ihat thcst Jdlcrenccs may rnvrdvc ilic genetic facturs. nthrr Rrnnrur: Natiunal Inslitutcs of Flcalth. 27

"OC('IIPAIION AND SMOKIN(: IN ('U1.1 Fi(iI? GRAI)1)AI1 S" 1)y ('arl (' Seltzcr, Rcscanh Fclluw in Amhroput,.Ky, 1'c.rtxaly Mutcurn, IlarvarJ lMrvcrsrty, arrd I),cpartmcnl of NutriU,rn. Ilrrv:uJ kh,Md uf )'uhlhc IIcalth, Ilustrrn, Mass, lou+ntrl o/ Applied l'tyrlro6rKy 4H/1.1 6, Febtuary 1964. "(X'('l1PAl1ON ANI) SM(1KIN(i IN ('O1 1 EGI: (iRAf1l1A I I•S" fly ('arl (' Scltzcr l'+vrholuRaul Rrvicw 71/I:I-I8. 1.uruary Vchruarv 1964 lhe results of a study of 895 nxmbers of the Ilarvard ( lass rol 1946. thirteen years aflcr gradualicxs, with respect to Ihc associatiun of ttccupa- lic)n and smoking bthavior, indicate tlatislically signnccant ddlcrenuatuons bctwccn smukcrs and non snwrkers; belwecn t'iKorelle, crgar, and pilx snwokcrs; and in accurdance with ckgtte or rate uf crgarcllc snrukrag Ihe significance of these findings a(Spcars lo relale 1u the influence uf Lcrson- ality and conslitulirrn un smokmK hchavirx. Smukcrs ate sigruficantly murc heavily rcprcuntctl in Ilusmcst ('unt.rcl (pnxnotcrs, salcsmcn• rNail and wM,ksak dcalcrs, buycrs, etc I and in thc held o/ ( Irg,rnrr.rntrn as a whrdc• as wcll as in tts subdrvtsuro rrl husrncts exccutrvrs rd all types Nun-smt,lcrs, un the tNhrr hrnd, arr sil;ruficantly mtrtc hcavdy rcprescnlcd in the licnrral ('ullural gruup c"nvtung rrl auurneys, collcRc prufcssurs• ckrgyrncn. tcachcrs ut high and rkmentary, schrNdt, anJ ctl.cctally in the "r,rhrt" Krncrrl culrur.il suhJivtsutn (p,ur- nalrsts. Irhraruns, rnuscum curatra., cth ) No srl;ndreant drllcrrnccs are apparcnt I-rtwcrn .nu,kcrs and n„n in„Irrs in thc I rchn„h,Ky• Ou1J,ru. Scicnce, anJ Ails an,l Vntcrlanuncnt Kr,•ulunKt, wnh the IM+ttihlc r>ccpuun of surgcuns 114.11 trm,krrt havc nnuc than Iwrtc thr Ianl,tnw,n of .urKcons Ihan srur,krts, wilh ncc d,llcrcntc tl,...ly alwl.ru.rthtng Ihc S^S. Icvrl ul siRnihcance lhe OrRrnirawm clmtd,tat„on, c.rn,l,Idred by the majr,r and minor eueculive sulKhvttuunt• dishlays an cutctt of crg.rr :rnd ciKarcltc sm<,kcrs over those e>;pcc'ICd• and a drfrtrency u( pipe smukcrs Ihc (irncr:rl ( ul- lural group eshd,rls a particularly large csccts uf prl.e smukcrs .nd a Icwcr Ihan espcctcd ptu(wrlNm of cigarcttc .mukcrs A(rorl fmm the Icntkncy for research scientists to kan luward Ilx pipe and crKar, and thc iuhjrcls in the field of Arts and lintcrtainmcnl lu snn,ke cigarcllcs only, thc rrmain- ing occupalicxtal classificalitmt arc not cs/xcijlly distinguishcd as to Ihe frxm in which they use their tahacco I)ata on the rate of ciRarcltc snu,krng strikingly indicate a numhcr of consistent, graded sequences of arrangr•rncnts trf the rrccupatitmrl frcyucn cies ccr,rding to the rkgree uf h,haccrr ctmsun,fdirm 'l hus• with rcyard lu the Organiralirxr Rruup, there is a prurrrssivc rncrcrsc of (Krtr,ns in this classification as thr amrwnl u/ c,rnrct/c smokinr incrrascs. Ir,nn 114^. amrmg 1Mru snurkinR kts thr.n It/ tir..vcttct J.rrly /.rrtYressivcly t„ 4'111"S• in srnukrrs r,r 1 nr m,we (iicks 1 djy ( unvcrsclv. rrt Ct it ntr An.l (;rnrr.rl ('ullute thrrr Arf t unvslrnl rr.ulr,) ,k, ,rjtrt m rr, ul,dla,n.,l Ir. Inrn, rrt wrrh mcrrauJ am„unt of tnwkmy 1'ratliu,mt'rt of Arts and I ntcrl.imu,irH trn,l 1„ Itc r,rhrr ., ry fu-.rvy .m,.lt•rt f 1,1r ,no,ri 11.1( l. J:nly 1,y .n,uAcrt nI "i r. . 1 11 1. 1 ., I,v U 0 0 0 . i It is of consirkrabk import that the results (sf the analysis of our data indicate Qre ertistcnce uf sulislically significant differences in tobacco hahits. If indeed the particular fors of occupatiunal ddlercnliatirm do in fact rcfkct sr+me gcnerat rclalionshipmto Iac(ort of ~serxn+ality, then it be- comes reasonable In ccmclude that smoking behavior itself is associated with the individual's personality. To what eatenl our occupational group- ings have genetic implications is difficult to ascerlain, but the constitutional elemeM is not to be ignored. These findings reinforce the evidence of other studies which indicale that snruking hrhavitr is significantly influenced by hosl factors within the individual and hence represents manifestations of distinctive crmslilulirxral make-ups. '1 he implicalirwu of this slalement relative to the pruhlrnr of smoking with health arsd discasc are not irkonseyuential. "STI /11IES ON FI('rI/RE I)RAWINGS: STRl1CTl /R AI. ANI) GRAPI II(' C'l1ARA( "1VRIS7I('S " By I crrna Wise )rmes, Phl), and ('arolinc Iledcll lhomas, MI), Johns I lu{rkins I lniversily Schoul of Mcdiciru, Ifallrnwre• Md 1'tri'hiurrir Ouurrrrly $upplcmcnt, Volume 39. Part I. 76 11(1, 1964. ((:ranlee: '1 hurssas ) A total of 725 while male medical students u( the classrs ut 1952 through 1963 participated in lakin8lhe Ilurnan FI((ule-1)raw/ng Icsl, a rec- ugnized testing procedure for personality assessmenl for nrnre Ihan Ien years llre evickncc rrrldcd by this study supports the hypothesis th•al slnrclural and graphic characterislics of figure drawings can be reliably coded for psychrdrrgieal determinations. 71se findings show (a) that drawings of individuals are mcoturahly different on a variety of characteristics and (h) Iha(, drawings have a mul- tiplicily uf crrmhinations of individual characteristics which can Ix uAjcrrivclY idcnlified. l his study therefore can he regarded as a prnilive step toward establishing objective means for Ihe use of the Test as a screening device in pcrxsnality appraisal, that can be applied also to other types uf subjects. Further Jesrarch as a part of the School's long-term Study of Precursors of Hypertcntirm and ('rxonary f)isease.houW delernsine (a) lu what estenl rinKlc variabks or r onrtcllatirms of variables can differentiate between prsp- ulat' s of inlellrKent, healthy young adults and (b) whether mcaninglul n cnrrcluriuns with other aspects of Ihe long-term study will Ix revcaled. Or6f.r Rrontor: National Ilcart Instilule. "PR/('l1RSORS OF IIYPFRTENSI(1N ANI) CORONARY I)ISFASF. AMONG III:AI'171Y MF i 1)I('A1. S11/h1:N•IS: 1)IS('RIMINANT . VI/N(-11(IN ANAI YSIS I l)SIN(i SMOKIN(: IIAI/IIS AS '1111; ('RIII:RI(/N" fly ('.rrrline Iledell 'lhrrmas, lArnnld ('Lrtc Rrns, aml ('rrulyn 1) IlrRudrrrh" -m, Ik',artrnrnl of Medk•ine, )rrhns Itoyr4urt Ilnrvrr frly kh,Md r,t Mrthtrnr, IlaluuuNC, Md NulF.rrn u/ the l.,hus IL•r'4r.rr ll,.rprruf 1I5/1 114 194. August 1964 ((itan/cc. ahruuatl '1 hc famrly hish,ry and psychuhrfit-aI arakcup o/ 111t.11 whrtc malc mcdreil tludrnh in the clancs uf IY4H to 1961 h:rvc hrrn t.uclullv rnvcs ~r ,, 29 a~ ? .~ ~ U e

IigaltJ and di><umented. The smrding hihits trf 4R1) were dctcrmincd Srnuatuc varrablcs mcasurcd were hrrRhr, brrJv NnKhr, blrNrl prr+turr, heart rate, and rholrorrrd lrvrl. Ihc psythodtrgrcal varuldts drfrrrtvnn, unrirry, and anger were measured by a chciklrst of 25 lypcs of bchavnn tn hahrls of ncrvous tensron Ihscrimrnant function analysis of the data f.ermitlcd s/udy ttf gnwp- ings n( the sublects with respect to a number uf varrahIcs and dctcrmmation of whether tht rtrops were ddferent, how they were related Itr each othcr, and which varra~dcs are of nsost value in distmgurshmg bttwccn the groups. 1 hc men were hrst combined into Ihree gruups: 3R6 nttn smokers and t.ccasionxl smtrkerr, 141 heavy cigarette smokers; and 165 inlerme- dute smokers: Ir6hl and modera/e cigarette smokers plus combined smokers of cigarettes and other forms of tobacco. 'There was a highly significant diflcrence in the varrables sludied between non smokers and heavy cigar- ctte smukers, a smalkr significant rhflerencc between nun svnrrkers and Intcrmediate smukers, and no significant drRcrcnce between htaty and in- Icnnedrate smokers f rrr further dixriminrrnl analysis, the men were divickd inlrt eight gn'utn ( 1/ ?9h Idclung nun smrders; (2) 116 whn snrtrktd less than once a day. O) 70 who smoked I tu 1(/ cigarcttcs daily; (4) S2 smokers of I I to 19 cigarcttes daily. ( S) I Sp smokers of a pack or more daily; (6) 4) prf.t unolcrs; (7) h(1 smukcrs of all three forms ril Itth.cctt; and (R) 56 es smtrkcrs, ) cigar and 4 prpc and cigar smukcrs wcre JnrardcJ as trwt few to nuaturc Analytrs td thesc eight groups showed vgnificanl overall drflcrtnccs it apf.cutd that non smrrkers, tKcasirrnal smrrkcrs, and pipe smttkcrs lorm a ctmsttllalrun td rather srnnlar rrstrns, whrlc loiriter smokers arrd mircd smokcrs prtar In f.t quilc a hu atrkc and lie atwrut half way between rwm srnolcrs anti hcavy vnuktrs In MNh three g.uup and eight Rroup c'nrnf.ansrms, the nrran discrirni- n.nt functrun scrrrc of non smokers was at tme estrcmc anJ Iha1 of heavy cigarette smtrkcrs at the other In the three group ctnuparisnn, heart rurr and aniirry contributed most to the differtnnatfDn, in the eight group case, hrart rare contributed the most, with rhrrlrsrrrnl. Jru+nrbc prrrrurr aml anger conlribuling to a ksser cxtcnt. llx f.cf that Ihe groups are found to be arranged in a meaningful or r by the discriminant functitxt suppcxts thc crmclusiun thrt real dif- ( cnccs between Ihese groups exist Orhrr grantor: National flean Institute li. f.ardiot'nstrrrlnr I)IvMIsP "NISI(K IIFMI('^1. 1)I MUNSIRnIION (Jf III'InK1' tlI I Xlltil: Nf)tIS NtIRI•I'INI•/'I1/(INI: IIY AIt/t1 Nl tt(ilt' I 1111 ItS IN I'llltrr" Ily 1. l Anr.clrlnt Isclrartment nl I'hy.adnyy. Il-./nn 1lnrvrr uy Si hrwl nf K1rd,<rnc, Ilu.tnn, 1.(ats .Srr.n, e 14 1 51/1 Sltd, luly 1I, I'l6 1 Adrencryrc hhcrs in isr,lattJ rat ins prcfi.rr.ruons wcrc Jconrm0r.itol htst,Khrnritally by ntc.rns rr/ the furm.ilJrhyJr t- -nJtn%,iturn Icthnilni ln the presence of aJencnine triphosphale (ATP) there was a ncl uplake n( nrnepmtphrrne added in vitro by thc adrenergic filrcrs, prrKlucing a markcd increase in tissue content and a striking increase in 1he fluuresccnce trl the adrenerRic fibers In the absence of Al Ponly a slight increase in flutwcsccncc was observed when the tissue was caposed to high curtcenlraUUns of nurepinephrine. lhesc findings indicate that the norcpinephrine taken by the tissue hom the medium is confined to the adrencrgic fibcrs. 7 he need for ATT lcnds sup- lo Ihc view that this consl,cwnd is necessary for the binding of catc- rlamiocs within the adrenertte strxage sites. Or6rr gr.nrorr 11.S. Public Healah Service. "ME('NANISM OF NICOTINE INDUCED VASCULAR Rf?SISTAN('F. IN l lil? Sl)f'ERIOR MESFNTERIC- ARTERY 01: 'fI1E ('A'f " Ify 1 P I.on nd C. 1. Hrghgenbolen, (kparlmenl of Pharmacolu`y, ('ullege o/ Met~icine, State llnivcrsity of Iowa, Iowa ('ity. Ar.hrvrt lnrrrnornrnulrs dr Phurrnorrrdynumir 149/)-4:Jd5-)92, June 1, 1964 (Grantec: l.rxtg) NiccNinc has been demonstrated in a number of preparations Irt mimic the eRects of sympathetic nerve stimulation. lltis study was designed lu test !he possible mechanism of action of nkotine in an organ with dual autonomic nerve inncrvatirm-namely, the intestines. The vasnconstriclnr and vasodilator resprsnscs to inlra-arterially administered nictrtine were sludied in 55 cats. Guancthidine, bretyllium and reserpine inhibited the vascsconslrictnr response of nicotine and sympathetic nerve tlimulatiun. IiexarnellNrniunt bromide did not antagonize the respon se to sympathetic nerve stinrulatirm or to norcpincphrine but readily blocked the vasrsconstrictor response to nicotine. Ilemicholinium had no effect on the response to sympathetic nerve stimulation or to nicotine if the vagal nerves were not stimulated, but with vagal nerve stinrulation, it readily inhibited the vasuconstrictur action of nicolitse. (t is postulated that the vasoconstrictor resprxrse to nicotine is indirecl, and that the site of action for nicotine is (he vagal nerves; and that this represents an example of parasympathetic activity modifying sympathetic transmission. i "GLl1('nSE R1.(X'KA(;F OF NnN-FSTi* i RIFlFh FAT1 Y ACIDS IN- l'Rf:ASI: PRO1)l)('Ff) BY SMOKING IN IIVAI'IIIY ANf) IN ('OR- C)NARY Sl1HJF(-1'S" Ily Inuis A Snlufl nd 1lcinr SchwartN, Division of ('ardiulogy. Tcrnple llniversily Medical C'enter. Philadelphia. 1'a Amrr- iranhrurnal rrl the Afrdrral Srirnrrr 24?/S:SRO SM4, May 1964 ((:rantee St r1oR ) 'fhc Idasnta wnA rtJ hhw+.t rrtl free fatly acid rttlarnsrs tr gluttvst Irrading wtrc rltlcnnmtd in I 1 healthy and 4 dia1N•lie sul.jet ts od 1wHh uaes, .It hathrtual sm mkcrs There was no change in red hlrwal ctl( fatty acid cnncen'r,rtitm 1 lie percentage dn.p in plasnra frcc latty acid was appruximattly the same in thc healthy and in the diahctic subjects Frwrnr 71

/rrarr symptoms of shock occurrcJ in the normal when his hlrxxl sugar fell to or bcluw the fasling level but was still within Ihe normal range. A subsequent significant rise in plasma free fatly acid occurred only in the normal and followed the ma rirnum drnp in hlrxxf sngar. Smrsking failed to change the free (alty acid Irallerns after glucose Ioadie If mcotine's presumed eRec1 in promoting atherosclerosis is solely lhrou8T; a rise in plasma free fatty acrds, the present studies suggest that rcvcral picces of candy txfore smoking would prevent the alleged atherot- ckrolic effect of smukin~. Ihis does not, of cuursc, exclude the possibility of changes in spcciRc (a11y acids or nicolinc as predisposing causes d alherosckrosis In the li6ht of these observaliona, the suggested significance of the re cd rise u+ plasma FFA in relation to athcrusclUosis should be rc- ' cslitated. ther rrowtor.: Fleart Associalion of Southeastern Pennsylvania and the Ar(erse Oickkr Research Fund. "G(.(/(Y)Sf: III (K'KA(;F: OF i11F INCRFiASf: IN STROKF? VO( l1MF? PRUI)lK'f?1) BY SMOKIN(i." By havid ('. Mcrses, Donald Powers and I.cwir A SokrR, 1)cpartmcnl cs( ('arJkd.rBy, Temple University Medical ('enter, Phrladclphra, Pa ('ircufanon 29/6 82(1 924. lune 1964 (Granlce: &)IoR ) 7lsc percentage changes in thc cardiac output, stroke volume, and heart rate were cktcrmrnrd in seven healthy h.bitual snrokcrs after smoking two cigarettes, after intcavcnrius gsucox, and aflcr smrrking precedcd by glu- cuse administration No significant chanRcs (sccurrcd afler glucose There was a signifit ant rncrcasc in cuduc uurl)ul, stroke vulume, and heart rale after smukrnR Pretreatment with Rlucusc did not change the heart rate response to snrr.king Ncverthelcss, thc carJrac out(.ut resprrnse was dimin- ished This rkcrcasc was due to a block in the incrcase in stroke volume induced by smoking The results indicate that the cardiac-output response to smoking canmN he clraracterired by studies limited to the posl ahsorptive state. After all, the amount of glucose used in these expcrinsenls was less than one fcwrth of that present in Ihe averaRe American meal The inhibiting effccl o( `lucrne on the responscs to tobacco su~csl that thcsc may he nutrilional resprmscs rathcr than harnrful ones Our unpublished ohserva- tiops indicate that mild escrcise after srnuking prrxluccs an additional rise i"carduc rwtput and stroke vcslume OrArr grantor.; Heart Association of Southeastern Pennsylvania anJ the Arlene 1)ickkr Rescarch Fund. "I:RYIIIR(K'Y/1(' PllOSP/lOI IPllt I INOI 1 1(' A('ll) IN Iti(-111 M1(' IWAR/ 1)ISFl1Sl: . AN(1 IN 111•^1 111 "(/y 1.-urs A S~drrtl, MI), I'rr+ (rssru r4 ( hnrr.l Mrdkrnr, •nd (Irrnr S.hwarV, Mt), )'hl), Itru.r.lh ( trrrrnrst, Icnlldc I/nrversily Mcrlrcal ( cnrcr, 1'hrl.rlc1Phia, 1'a I unrrr 2 116R 1269. I)rrrnncirr 12, 1964 (Grantce: GrloH) 0 ~ 0 r The erythnxytic phcxpholipid fatty-acid contcnt and pattern were uuJ as markers in a group of patients with acute myrrcardwl InfJrclNrn and in a group of persons clinically and radiographically free rrf athcun- clcrosis to Jctcrminc whether the diets in the two groups had over a long peruod contained different propoxtions of saturated to unsaturated fally acids. Erythrocylic phosphotipid linokic acid, which tends to vary linearly with the Iinulcrc aciJ content of a diel consumed for six weeks or mure, was the acid which displayed the greatest individual variation. But there was no statistical difference between the two grwps in the level of this acid The investigation therefore did nol support the view that the cause of myocardial infarclion is a diet high in saturated fa11y acids and low in luraled (alty acids. i.r grentorsr (1 S Public Nealth Service and the Hcart Association uf thesslern Pennsylvania. 16 "STROKE VOI.(IMfi ANtI CARDIAC OUTPUT AFfF.R SMOKING IN '1111: P()S11'W1N1)(AI. AND IN TIIF: FAST'IN(i S I'A 11: .." Ify I.ouis A. Scdofl, MI), and Ik+naW V. Powers, MI), Tempk Ilniversity Medical ('enler, Philadelphia, Pa. Anerrican lot.rnuf ul the Mrduul Srirncrs 248/ 6.69) 696, Ikcenrber 1964. (Grantee: Soloff) Cardiac output and slroke volume were measured in eight healthy male vuluntcers aged 19 to 26 years, who were habitual smokers, in lasling state before and at IS, 30 and 60 minutes after smoking two cigarettes within 1(1 to IS minutes. The tests were made 30 minutes or immediately aftcr ingestiun of glucose; after drinking a volume uf water equal lu the volunte of glucuse solU(Nm; and without glucose or water adrninistralion. The results reconBrmed the obserYalnM that smoking incrcases the heart rate, cardiac output and stroke volume of farlin¢ habitual snsokers. (iluasx by moulh, whether 1•rken immediately or 30 minutes before srnnk- in,;, blocked the increase in stroke volume and cardiac output provoked by smoking, as previously demonstraled after intravenous administration of ~(ucase. 1 he water alune had no hemodynamic eRccls and did not in- hilrrt the effects provoked by smoking in the fasting slate. These studies suKgrsl that the physiological act of eating sugar pre vcnts the cardiac effects of smoking which may occur in the fasung state ilic cardiac reslwrnse to smoking cannot be fully charsclcrired by stuJres lin eJ to the puslahscsrplive slalc. r~(Irf,.r Rrnnrr.r: 'Ihc Arline 1)ickkr Glass Chapler of the Ifcarl Assrrcia tiun uf Sr)unccatrrn Pennsylvania . "I IISIVIN'S Mn( I()RMnfI(/N 1)IS(Y)R11ANI INI/tA('AVlIAR1' 1•11('If((u'nf(1)I(K;/(nl'lll(' ANII I'RI•SSI/HI: RI•1 A11()NtiIIII'" Ity Slanlry S Mrrlrs, MI), Willisrn I lacrrhy Ir , MI), rnd Ilrnry 1) MrIntursh, MI), t 'rrdirrv.r.cular (.atKUaruy, (luke (fniversrly Mcdreal ('rn tcr, lyurham, N(' .(nt.rrr rrn l.Ournof uf ('urdiuf.rty 14/S.721/ 712, Nu vcrnber 1964 (Grantcc'. Mclnlosh) 33 31

Althr.uEh Jcxtifsed in 1966. tthe diaRnosis r>t Fhstcin's malfrxnulion wat nuck erc1usivcly at the autr>(+sy tablc unul 1950 Srncc thtn a clinical Qrcture hat cvulvcrl su that tht ihasuosrs may be strongly suspcclcJ rrn the basis of roulinc evaluatir.n It may tsc cr+ntitmcd by cardiac cathctcriratinn lhis case Jrmr.nsttatcs that mKmrl atrul inlrrcardiac clcctrical com- ple>;cs and ptessures can he ot.uincd in a paticnt wrth Fhstcin's n+alfurma- tn+n d thc Irp of the clectnKk catheter is withdrawn through that porlion of the vilve attached trr the true annulus of the tricusprJ ring False negative as wcll as previnusly reporlcd false pr,sitive trscinKs may hc obtained ('areful anaa,mic kscalizalion of the IncusriJ valve is rnrf.crative in patients tuspcclcJ o( having Ebstein's malfurm.ruun. llse JraRnu.rs can also hc cssnfirmcd by the production of vcntriculat cxuasysir.ks nr monu- "alrial- Phasic ventricular compktes when the ekctmde is pressed against y(d" ventticular enckkardium. L//OrAnr gr.rrtor: Nalirxsal Ileart Institute (2). "Nl1( 11:1(' A('Ih ('ONII:NT OF 1ltRKEY 11FART W1l-Ti A NOTE (1N III-MO1)YNAMI(' FINUINGS" Ily Rrrf.crt (: Sumncr, Mf),'lhumas C Iluyk, Ill. Itcnry 1) Mclnto-,h, MI1, and Rubcrt Fi. Whalcn, MI), ('ar- drovaxutar l aMxatrrt f)uke llniversrly Medical ( enler, I)urham, N C. Imrriran !r urnu! u~ rbysrulncy 2p7/S. 11U2-11f16, November 1964. (Gtanlce: Mclnfosh) In order to stuJy the marked Jisparity in the thickness of the kft and tiRhl vcnlriculat walls rr4 the turkcy hc.ut, ckso.yrrhunuclcic acid (1)NA) and tif>tmuclcir acid (RNA) and rrnlcrn contcnt of the kft .nd righl venfricular rnyr.cardrum were JclrrmmcJ in fuwl, .rRe 4, 6, and I I weeks and at maturity Tlse 11NA conccntratxrn in the riKht veniticular lissue was found to be significantly greater than in the klt vcntrKulrr tissue in each brtd of caoh age lhe 11NA cuncentr,liun of fxrlh ventncles, hrrwever, dt:creased with increasing xe Prrdein esstseentraurrn in fxrth venlricks increased as did prufcin/1)NA rali(n Although RNA crxxenlralirrn shrswed less cunsistent chanRcs with aRe, the RNA/E)NA r.tirr incrcascd II was corsctuded !s a result n( 11sexe studies that the prcdr+minanl ccllular changes that occurred with age were Ilx resutt of hypertnrphy. In addition tn the biochemical dettrminalions, ekclrncardirry.rarsss and hernodynamic data were ubuincd on birds in rrch Rroup. Although pol- monary artery pressure is con,pauhk Io that of othcr laboratory animals, a markcdty ekvated systemic hhwxf rressure dcvelr.rs in Ifse turkeys he- Iwtcn the ages of 6 and 1 I wccks -1 he role ul hypcrlcnsirrn as a Jelcnninant 6/ ccllul.rr size in the left vcntricle was not elucnletcd by this study (ltflrr Rrsntor.: National Iltsrt lnstdulc anJ Anrrrrr'an Iltart Assr,tr.rli-m ~., rn ~ ~ "AR IfRIAI A( It) M11('(11"t)l YCnt ('1lAR1U1: ('11AN( :1:.C 1fY I'Rs) I AMINI• " fly Irr 6"rc, k11), Hu0un 1 rniversny tia h~«rl of Mr•drr mr .rnJ Masuchuactts Mrrn"rral llr++f'rlnls; Yrrknr Ianak,r, MI), M~ssarhuscfts Mtm(qul flosf+il+ls, and IlrtulJ A Whitc, 1s11), llarvard IvlcJical Sihrr)l 1.1 P ? t and Veterans Administration Hospital, West Rosbury, Mass. Archivrr of Pathufoxy 7Rl3.lbl-IR5, Septcmbcr 1964. (Grantee: (:ore) After the repealed administration of prolamirsc by vc+n over a 1wo• weck pcrird, the putmonary arteries of rabbits display a 50% augmenla- tinn of their acid mucopolysaccharide (AMPS) content. AlthrYuKh each of (hc specific AMPS moictics par/icipates in the increase, there is suggestive evidence of a shift in their relative proporlions; hcparitin sulfate incrcatcs and chonJroitin sul/ale H diminishes. A smaller increment of about 20% was observed in the aorta hrrt was not associated with rectsgnizabk mnrpholasie alterations. E)espite the idcntity of the estraction proccdure. the f+nal yickl from the esperimcntal aninsats was not as purc as that obtained from controls. Substantial in- creases of reducing sugar and of protein were found suRResting a SI)co- protein constituent of the acute pulmonary arterilis which occurs in these rmsls. Olli.r R "U(.CERA flON OF ANf) EMHOLIZA-r10N BY AT11F.R(IMATA " fiy Ira Gore, Massachuse/ts Metrsorial Huspitals and Hoslon (Iniversity Mcd- ical C'entcr. ('hapter in "E'volutit„s of the Adxrosrirnrric Fluqur," R. J. funcs, EJtttx; published by the University of Usicago 196a:315-33:. Ukerated alhernmauws plaques re a eomplicatwsn of advanced imimal disease. 1'hey occur mure commonly in Ihe arteries of prrpula- tions affliclcd with a high incidencc of alhettrsckrMre Jisease, and they Icxnt a greater proportion of the intimal process in "coronary" than in "ntmrrxunary" deaths. Factors in the development of uleeratirms are mechanical stress, ischemic neerosis, and hemorrhage The conseyuences are an enhanced tendency to lhrombosis; weakening and atlcnuation of the media, the essential mechanism of neurysm formaliun; and the rckasc nf alhcrumalous debris into the circulation. Such debris may occlude small arteries in various orRans l he Irc- yuency of alhcromalous emboli varics with the extent of the ulccraled ksiuns; they were uhserved in about half the patients whu had aneurysms of the abdominal arrrla 1 csiuns are mo.t eommtmly observed in the kiJney, spken, and pancreas. Itypcrtension and aznlemia arc frequent findings with renal invulvcment As shnwn eaperimenttny, they persi%t frr many munths MyrrarJial infarcts and/or cerebral infarets are cutnrnnnly presrnt in tlxst palicnl, hrA rN+ly e.ct's( iw.nslly can Ihey be shown tu he rhrrt tly rrlrtrd tn athrrlMrnlMrlk• Invrrlvcment of the erarmar) anJ,hrr crtcbr.J urlrtir% ('rrrl.rul arlrrul a/htrrrtrulwrh are astrt•iA/rd wilh r hiKh fa~rtr rr tnrn M anrurysm% ur thc Ivrrairu,rl aurta ('nusrderinR the usrrat u•vtrny of athcrrr.rlcrusn us Ihc aUArrminal anrta, invulvernent of tFht Inwcr rit Iremiurs secrns rclarivcty uncummun. In parl, at leasl. this re/kcts the in- he uency with whah the Icfs are eRamined at aulupsy thrr Kran/nr: Natinnal tnstilutcs nf llcalth. • 35 ranror: National Institutes of Ilcalth.

"OI1SF.RVAT1(1NS ON TIIP_ FAlf: OF ('ll(11.1?S1FRO1. F-MHOl.l." By I(iurc, FI 1.. Mc(bmbs and R. 1.. Lindyuist, Pathology Ikpartments of the Ntaton l/nivcrsity Medical ('cntcr, Massachusetts Memorial flos- Fitals, and the Peter Efcnt Brigham /luspilal, Bnston, and Veterans Admin- rtUattnn l lospital, Wett Rusbury, Mass lournvl u/ Arhrrurcfrrnsrr Nurarr h 4/6:327-5)S. Novcmber l)e+cember 1964. (Grantee: (itxe) Following intravenous adminislratit.n of a su%pension of fine crystal- line chalestcrol in hrinxdosous serum to rats and rabhits, mullipk cm(xrli are found in the branches of the pulmonary artery. Farly they are associated with thrombosis and a diffuse as well as focal inflantmatory reaction of the vessel wall. Thc intrinsic acid mucopolysacchariJcs particjpatc in this pnx- ess. A prompt kucocytic response to the crystals early hecomcs mononuckar and foreign body giant cells appc ar s soon as 24 hours. licfore the end of the first wcck crxh)thclium has grown over the crystals. Smaller ksicsns become estrutkd into the alveolar spaces and these become fewer with time (Nhert become encased in fibrous litsuc and may slowly prnelr.te the arlerial wall to /tc in the adveMitta Fvcn after 4 months in rabbhs and 9 nyrnths in rals, chtdcslerol crr stals td embolic origin can ttill be dcmrxs- tt acd in the pulmonary arterial channtls. rArr gr.nror.: (/ S Puhlic llealth Scrvice and Massachusetts I(eart . ASttK1alK1n "111F. AN fA(;()NISM H!:1 WFFN NI( Uf INN AND M(1(Y)POI.Y- SA('('IIARII)li A(-I IVI IY " fly 11 1 Whrtc, MI), Harvard Medical Schaol, I(iorc, t•11), ll.,stom Ilmvrr"rv 1,h'.d .4 Mcdurnc, antl Il 1 I.arkcy, AH Vttrrans Admirn%tr.rnvi Il...Wr,t R,i.htuy, Mass Nrurhimrar Nroltoria crrrrmrnr.irr 1 J )lu! I1h, IWr1 ((irantcc Gire) In tuaminrng htwitytK ttrvrtt it has hrcn ,h,-wn that nxrlunc in• hibils Ihe ht{~arin ( nr other AMPS ) NmiuljtrJ.Ic.nng at uvuy ( as mcas- urcd uptically) tit the rtlcast of nrm c.tetncvd Litly rtid rn tura Meas- ured in vivo, howevcr, clearing factur activity hut not non cstenhed fatly acid producing activity is inhibited It would seenr that nicotine in small quan- titics aNcctt this rekasc of the lipolytic enrynte In larger quantiucs, though, nictNine Iso inhibits the prc-furmed enzyme. Clotting studies show that nicotine nlagonizra heparin both in plasma nd in fihrinogcn thrombin mistures. 1 he authors have no chemi- cal evidence of an interaction to esplain these (unctional antagonisms. "INFl.(/f:N('F? OF CORONARY AR1FiRIAI. PRI:,SS(/RF? ON (Y)R- ONARY VASOMUl(1R 1UN(1S" fly ('ccd V (-ross, Ikpartmrnt of Medical Research, St Joseph 11011F.1131. Burbank, ('aldtania ('rr.rd,nu~n Rrrran•h 15/2 Supplcmcnl 1:87 9August 1'161 ((iranlee: P F S.lis- bury- deceas.ed) 1ht tx•havna of the ctxonary vcssrls in Irrnt% n( cornnary vamnu4trr t rnus has been ctamrncd in dugs lo assisl in Ihc study of autirregulation t><curupary hhxxl flnw 'ihn auttxegulattun hccirmcs evitknl by a relatively constint fluw alicr chanRes in coromrry artenrl la.ssure; in this study it i was observed only under conditions that separated central coronary arterial pressure from atxtic pressure. ('kat evidencc of coronary autore~ulatioo was not observed when aortic and coronary pressures varied to~ethcr and the nervous connections of the heart wcre preserved. When the performance of the heart, systemic arterial pressure and central coronary pressure varied within physiological limits, changes of coronary flow appeared to be determined by variationa of coronary pres- sure. Ilowcvcr. it was not possible to decide whclher this constancy of coronary vasomolor tonus was due to an intrinsic property of coronary musck, such as reactive contraction in response to stretch or to rvout or otbcr rrsechanisms. Ot/ler gra,.torr National lleart Institute. I "N(K'LEAR RIi30SOMFS, AN EARLY FACTOR IN TISSUE RI?PA- RATION." By S(iwfbprnas.xr and C. IJc Schryvcr, Wayne Slak Uni- vcrsily ('olkge rr/ Mcdtcine, and I/arpet Ilospilal, Iklnrit, Mich. Bio- cArmiral and Biuphysica! Research Comnsunicmiont 11/1:12-16, 1964. (Grantee: R. 1. [fing) Myocardial infarction was produced in dogs br ligation of branches of the anterior dcscending coronary artery and glycmt-2-C" was injected intravenously. 1?re animals were sacrificed at various intervals afler in- farction, from 4 hourt u~ to 6 dayt, and cell fractionation and nuclear eslraction were performcd. llse data scem to indicate that immediately following infarclion and destruction of myocardial tissue therc is a rapid response and renewal of cell material replacing Ihe nccrotic musck. The early renewal of cell material was further indicated by the incorporation of labeled Rlycinc into nuckic acids of the infarcted tissue. The first step in the reparative process seems to he synthesis of nuclear material, followed by reconstruction of mitochondria and microsomes. ~tAar rraetorat U. S. Public Health Service, American Neart Association, Michigan lleart Asscscialicsrs, I.ife Insurance Medical Research Fund, Bunou6hs-Welkome Fund, and the John A. /lartford Foundation. "MY(K'ARf)IA1. PROTEIN SYNTIIESIS IN CARDIAC IIYPf=R- TR()PIIY." fly Sigmundur (iut)bjarnasat, Michael Telerman, ('hiyo ('hiha, Paul 1.. Wolf and Richard 1. Bint, Wayne State University College of Medicine, and Harper llutpital, Delr,oit. Mich. lrrurnaf u/ InArrruaay and (7inirof Mrdi, nv 61/2'.215-23), February 1964. "PR(Yfl?IN MI:IAIt()I ISM IN ('ARIIIA(' IIYPI:R'I"Rt)PIIY ANt) /11?ARl F111 I//(1? " ny Sirmnndnr (it/dh)afnasMM, Michael '1'clcrman and Richard I Hing Arnrnron ltwrnal of PAyfi.duty 206/2:294 298. Fcbruary 1964 ((:rantee. [ling) The rale of rnytx-ardial protein synthesis was studied in the hearts of nornul rabbib and of aninrals with esperimenlally produced cardiac 37 16 P O P