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36 CTR HN 011360

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ti(:IF;NTIhI(: AIWIC(/IIY 1t(/A111) to the Tohacco Industry Research ('ommillce . KI:NNI:1'll MURRII.t. LYN('F1, M.t)., Sc.l), 1.1..1)., C'hnirnran 1'rrti.frnt, 1)ran of Fnrulfy anQ 1'rnlrtrnr nf I'mhnlnqy McJical ('rdleRe of Sou1h Carolina ('harlesu+n, South ('arotina RIC'IInRI) 1. I11NG, M.h. I'ro/etJ.rr orrd l'hninnan. Department of Mcdicine Waync State Ilniversity Collese of Medicine Ik(mit, MichiPan McKr1" , N CATfPI.I., Pn.D., M.D. I'ro/rt.rra F.rnrriwf of Phnrmorolrrgy ('nrncll I lniversity Medical (b11eRe New Ynrk, N. Y. ful.luS 11. C'OMR(1f•., la., M f). INrrrarr, ('nr(linvascular Research Instilute University of ('alifornia Medical C'enler San hrancisco, ('alifornia (.1?ON 0. 1A( Y)IISI)N, M.D. Pr.,/rrmr .r/ Mrdir inr, llniversity of Chicago I)i.rrtrrr, Argonne Cancer Research Flospital ('hicngo, Illinois PAU1. KO11N, M f). I'rofrrtnr of I'nrlrnlogy Ilniversily of SGrolhern California. School of Medicine l.os AnReles, California C'I.ARrN(-f ('CN)K I.Il-11.r. Sr.n., 1.1. 1)., I.ITT.f) Srirnnfir I)irrr-rnr, Tohaccrn Induslry Research ('nmmitlee I)irrrtnr fnrrrine.r, Roscoc Il. Jackson Memorial Lnbrrralnry Ilar Ifarhr+r, Maine SfnNt fiY P. Rf;IMA NN, M n., S(' h. .Srir.uifir 11i.r.t.N /inrrritn., The Institutc for ('ancer Rcsrarch 1)i.rr rrn Fnrrrirrn, 'I he I.ankcnau I Iospilal Rcseart'h InstiNrlc F'triladetphia, I'cnnsylvania WII I.InM F. RIFNIIOr F, Jra . M.h. .1 rtrH ialr 1'rn/rrvn n( SurRrry )rdrna tlopkina Ilniversity Schnrd (if Medicine FI.iItirurrrr, M:nylanJ f:hWIN It W1/ CON, f'rr 1) . I 1. 1) l'r.+frrtrrr lrrrrrilrrt o/ I'Ilnl PMrttir 1 I I.rv:urt I lnivrr6ly ('~mhri l~e. M.res~thuc~tls Ittrltl'ItI (' It/x Kl I'1, 1'rrl) 4 r1.,i r,ur No rrrrrrh, Itr.r~ hn

CurrClit Statiis of ''o l~~~ccc~-I Ic~iltla SIiiclics Preface lhc cllral Ir+ rrl•I.rin new km+wIrrlt-c r+f Ilrc rnil•in nnrl nalnrc (if the tn callcd cr+n.titulinn.J rrr chrnnii rli.r.rtrt it wiJc tl+rcarl \vlrat ,rr Ilrc I+rr+hlcmt~ Wh.rt h:+t t+ct•n arcrun/dOhcrl :+nd wlrat rrr rn.nnt I++I•c .r+rrl•hl (r.r, rlrttr+vcrnl :rml .+n.rlv?rrlr Vrry rvrrlrnllv n++ cr+n+l`Ictc dnlNl'rt tr+ Ilrctc yrrrtlir+nt t':+n yet hc rrvcn Onc n+.rv, hrrwcvrr, cr+nrrnr.nt r+n t'cr/:rin cvidcnce nf hrn/•rctt snJ drantt trcnAt :+nd Ivr+al+ct'tt th:rl tccrn tn thc wrnthy nr aIlcnli+rn It it hrrl+cJ th:rl Ihit Rrpr+rt will srrvc Ir+ m:rinliin am1 tlin+ulatc inlrr- ctt in, and .nlq+rnl rrt, Ihe vaw ~nrnmrl yd retr•:rr+h Ihat ttill ncCrls In hc rhrnc hrhrrc r+rrr knnwl+'rll•t' -.1ml tctlrni,lnrt c:m t+rnlrrd t+r ptcvcnl tht-tc ditratet At Scientific 1)irct'Ir+r, I thr+nlA Irkr Ir+ :rckm+wlcJl•c Ihc dcvnlrrl and untcllivh c/furt. (if rny attr ci:rlct t+n the Scirnli/ic Arlvitury Iln:rrd Inrl :rltrr Ihc crw+l+cralinn anJ crcalive cr+nlrihuliuns r+f (nr granlcet anrl tcicnlific crrntullintt I thrnrlJ :rltn likc tn cmphati?e 1/•nin the vilal I+art in r+ur whrde cflral plivrd hy all mctnt.crt rd the lr+h:ucn Inrlustry Rctrirch ('nnm+il/cc in rrnvirting crmrf+lttr frrcrlmm ilf rl:nurinF and :rrtirrn In Ihntc whr+ :rrc rctrr+n.ihlc f-n its tr icnlifii rctc:nch I+rr+r.r:trn (• (• I iltle Sticntific I)ircclnr 1 he r:rt/ ycar Irat rrrxlucetl an inleresling and prr.vtx'alive Si/ualirm arisinR frnm thc activilics uf different rese7rch wnrkerx indrl+endcnlly in- vetligartinR Ihc prrttihlc trde ttf smrrking at one nf many Lrcturt hcing t/udicd in human health prrthlcntt. What haprc•ncd in 1V54 was the aprearance of many mnre retearch findinRt anJ cnnmtcntt clearly thrrwing the uncertainfies anJ Jivcrgcnce nf npininn amnnR dnctnrt and scientitis in rcgirJ ta tuhaccu and hrahh. f)ivertily (if resc'.11rch pnrlrlcmt and tf,eculalir+n ahnut Ihem have rxitlcJ tince 19Sq, hut in Ihc patt year they became more rnarkcd in :rrliclct anJ ditcutsirmt rrfrrrinP frr tmr,king. lhcte Ihinl•t, nf cnnnc, t+/ten charActerise nny phate of a cnn+IdrR rctc:rrth lunblcrn :rnd trcnr In atise esrecially at the slarc whrn the urge Irr srrlve :ury rrul.Icm cr<ccclls the knnwlcdgc neccstary hr enahtc ns Irt dn tn. 'Ihit it m+1 a causc ftrr alarm t+r fumlamenlal ditlurhancc nf any kind. It it Ihe rt•flcclinn nf natural cvnlutitm (if trur knnwlcdge .rf the prr+l,- Icnr and ilt cllcct npnn Ihc Ihinking nf the f+ctqde cngagcd in efinrls tr+ fiml ilt tnlntit+n. TIIF.I)RIF.ti ARO11T Tn11AC(:n nt an eRanrple (if snch cvrdutirm, we may cile tcveral Ihrnrics Ihal have Lccn f+rrttul:rtcJ in ancnrrtt Io eapl:tin the limilcd J:rla Ihat alry.c:v In indic:rlc the tnf+fMrtcdlv harrnful eflca'Is nf tmttking, esrccially wilh resprcl Irr c:rncer rd Ihi• lung On prescnt eviJcnce• any tine nr somc cmnl+inatirm trr Ihctc crrnct•ptt, r+r (if rHhcrt yet lo he nffcrerl, ntay hc Irur, r+r m+ne (if Ihcm m:ty Irc. nnu+ng thcse Ihenriet are: 1Yrrnry 1. Thrrr are tb.nse rrlrn nrgRi.t Nrrrr rnnv br rnrrin.r• Rrnlr .rrhatnnrr. In roLnrr.r .nnrfrr t/rot nrlK/rr rnnrr lirrmnn /unR rnnr.r• by rlirerl nrllnn, f'rnclically Ihc trnty tufif.rvl for Ihit theory is Ihc rcaclinn nr Ilrc akin nf snmc I:rlwxatnry animalt, nnlahly certain mice. In the af.plicalinn (if crmct'ntr:rtcrl cr+nJrntalct (if trrhaccrr tnnrkc prrahrccd I+y r+nr nrcchanic:rl rh•vitr nr anrdher I Inwever, nr+ .rrhuancc h:rt f.ecn fr+und in f++l.act'tr smt+ke in yu:rnlitirt suflicicnt Irr accrrunl /r+r cven Ihc rntrute tkin rcaclirmt that h:rvc hccn rc fwnlcd AIttr, /hcrc atc many rr•lanlt t•t runutc akin I+aintin0 ct/rr•rinn•ntt th:rl dirl n+H rctnll in Imn+at 6

i Repeated etpcrimenlt in this cnuntry and ahrnad in which laboratory r.nirnalt wrre induccd to inhafe trrt+.rccrr cmnkc I„rrr fnrlyd n, pr,,,h,1 r n tinqfr IunR cnnrrr of thr rypr that it prrvnlrnt in mon. It it Rcncrally accertcd Ihat IunR titwe rrf mice ic mmore c'rxnfi:uahle in lunR littuc ..f man, anti that tmr.ke directly a(+rlied to the IarRrt titauc hy inhalatir.n it mrnc like the actual pnK-ctc t+f huruan tmr,kinp than is Ilre arpGcati,.n rd heavy thnet of amoke cnndencatet tri mt,mc skin '1 here hat been growing recognition of Ihe irnfautance of nce cn<alkd negative evidence r,htaincd from inhalatinn cxrerimenta. flhr work of Pattey, described in the report af the 11ri1ich 1'mpire Cancer ('ampaiPn, iuued in the summcr t.f 1959, made this clear and gave aclual inctancec nf the ea(+crimcntal work th.ne. Scicnli.ta and the puhlic will recrrRniYe that there is mrnc dirccl and applicahle evidence in thit inhalation re"arch than in the mnuvr tkin riinlinR lyf.c nf wrrrk 7lvu.~ 2. S,.m• r.rrans hnl,l thnt rnrohe nury nrt no nn lrrl. fnnr rnntrlLufinR tn N.• in. rrn.r.f prob,,hifirr o/ n.nflRnnnt rlrnnR.r fhnt pr1mnrify r.urlt from nth.r intrnrsflrJnr /nrtnrr. Thit ther.ry, e+.cnlially hated r.n Ihe atsumptinn Ihat tobacco may have a cnntrihuhny effccr, hat not been cfudicd In any Preat degree and therefore nccdt further etplt.ritir.n and tcttinR lhc varirrut methtklc r,f actayinR the cRectt of tnh.ccn tmr.ke mutl he invcttiFMcd furlhcr to find nut whelher thc rearc,mrt of the larpct fitsur are q•rcific for tobacco .mr.ke, or whether they rcprctrnl a Rcneral rcactir,n that may he ttarled hy a number of different inrernil anrl!t,r rtternal aPcntt Thrnry 3. Snrnr ruRRrrf thnt rtrr.ar. .nrnkintr prn,lnr.• n "Rrnrrnl .frLifity" fhnt inrrrnrro thr prnlrnhifity nnrl Irn.frn. Ih• npprnrnnre n/ n whnle nrrnv of LnthnRrnir plhrnnmrnn. lhe lerm "Reneral dehility" is r Irx.ce nne, and tuforlortrrt ol thit idca are unahlc tro rkfine it 1)chility may be cnutcd in different Lce.ple at different timrt f.y different circurnctancet and difTerent aprnrc 11 nrly dcccril.c diflerrnt types and dcRrrct of internal dicturhance and unhal:tntc Altn, "etcetcivc vnrrkinR" aml "ctcccc" in any other human hahit arc furlher vatiahlet Ihat niake this Ihcory difT'icull tn prove r,r to di•prt.ve, nr even to define in a concrete anti analyyahle ft,rni What rnay t.c °eitcet." for rine pcrtnn may nr.l, in any eppreciahlc way, anerl fhe phycinlury nf another If tnhaccn is t.t be clittifird in the catepory of ar.rntt that pnalnce "Pcncral dchility." it will join e whole hr+.t rJ r.thrr arrnta and inffuencct that prr%urnallly can dn thr tame. To .rf..rarr t{hr I rflrt tt rd Inhat, ~, fl,,m rllrt It .d .+thrr thingt will (6 he a must dillicutt latk and will require a great deal c,f planning and ac- cumalatirm of fundamental rrsearch to find out what really are the fxst mcthr.dt of ataay. Thit f,arlicular concept secnn Iu have originated in an effort ttr inler- firel the reported claticlical ata.clatirm between tnhaccn use and various ailments ftir which there wat nit satitfaclrwy evidence of direct caucation. TRrory -1. Th. rlr/rr.e of u.e n/ fnhnrrn mrry b..IJnRnnrtir n/ fyp.s of p.r.nns orhn hntnw dfff.r.nl health ri.kr Lrrnu.o n/ their fnnnle nnlur., or IIr.Jr rntr of fir- InR anti r.nrFlnna to fR• rvninna pfry,lrnf, mrnrnf nnd •mnllonnl rbnfl.nRr•s nnd alrr..rp of li/.. The data concerninR this theory have been accumulalinR rather raf,idly and frr,nr a nurnhcr nf diflercnt aourcct One it the cnntinualinn r,f ctudict t.f fhum;.n Iwint, h,rlh idenlicad and non identical, that indicalc a c..mlifu- lirrnal factor Ih..t may influence smr.kinR habits. Recently f..ur Swrdith tcicntitti puhlithcd a ttudy Ihat in many ways parallelcd .rne Sir Ronald A. Fisher ref+ruled lact year.'Iheir study cante In the cirnc cr.ncluciun. Ihat he did, namely, Ihat irlenlical twins more t.ften had the same tmr.kinR hahilt than did nrm-idcnlical rwinc, even Ihough Ihc degree tt, which hrdh lyrct of twint encountered a tirnilar environment wat cascnlially thc sarne. Other dala have conic from tcveral types nf psychohoRical lesls that are heinR Riven in "captive" pnpulatinnt of people to find oul the mental and emotional Irailt nf smokers and compare Ihem with thr+ae of nnn- tmnkerc. A recent paper reported on certain significant mental and cmn- linnal differences between the two categories. AllhouRh ilt nuthur did not interpret it ac cnnclutive Ihat Ihe type of pertnn is an impralant faclnr in Ihe titualinn, 1he fact remaint that a difference was demnnctratcd. 17rit difference will have tr) he e.ldained and evaluated ahmR with other aacn cialionc of a clalialical and semi-alalitlical nature. 'fhit last Ihrray rcally indit-alec thal "e><ceaaive" snu,kinK is aymptr, matic nf a ccrtain type nt types of rersnn and is nur a fximc fact,.r in crealiny nr ealahlichinR the types nf f•crsnnt wh.o are had health risks 1 hcrcGae, il is nrH an arrcalinq In Ihtne wht. arc hlcJl•cd Ir. auhtl:.nti:rtinP a caucal relali..mhip We find Ihat we now have nt Icatl thete (nur theories, Ihe ahar.lute and relative inrpontantc td whith is uncerlain ru unknown We dt, n,.l Arrn.r•, and rhnt iS Ihe inrla-tant IhinF tu rememhcr, Furllrer rrtrarch il neede.l '1 he far.rnr .ituntion indit'atet Ihia UrrerlnlvnCally, nn.I it lanvr. Ihe witd.un nf tlir a11r1uJr rd ..irn/ific c.marrvntianr I 7

l)ftSF;R1 ATIONC l)N llF,tiF:ARf.ll In the 1VtR Rrp<+rt il wat fx+intcd <+nl thm the prnponentt of the Ilhrtxy td i Irrhaccrr link 1<+ lunp t:urcCr hit/ rCatcd thcir t'Iaimt nn a"Irifx+d" td d.ita - ttitklica, I+;+Ihtdow, and animal c.l+crirncntatinn, In file patt «vera ycart r.1th IrR td Ihc "Iril+ud" Ihac hCcn arhjccl In mrrrc an1 ntnre uC~~ncttct• analytit by inrlcl•rnJcnt invetliRatnrc whtr havc I+oinlcd t+nt thr dcficicncict nnd ctcn crmtrnditliuns in the recultt Rl.ti.tir. hurinF Ir150 adrlitinnal slatictical mnlrri:rl rcpr+rting in atax'iatinn Lctween snu+kinR intl certain ciutct t+f de:Nh aprcircd Itr t+c muth file tame ac earlier dara. Ihcre wat ctmcitlctahle criticitm nf the ctmtlucir.nc drawn frtrnr Ihic tyf+e nf tlalictital w<rrk whcn file nriginat dala al•liearcd antl /hit criticitrn hat ct+nlinued. l wn intlivirhrat in parlicular hivc fnr urmc yrirt been ch+trly .nalyz- inR and cnrnmCnting tm Ihc tlnlitlical wnrk arnl thc trvcr intrrl+rctati<tn t+f it Iha hat f+rcn t<+ writ (+uhlit'ircd I hetc are 11r 1rnCl+h Flcrkarn, head n/ file Section nl Iti<+mrtry and Me<Iical,Ctatittitt :rl thc Miyo ('linic, R<x hecler, Minn , and Sir Rnnild f ithcr, a horrncr Arthtrr Ilalft+ur prnfcctt+r of genctict at the tinivertily nf ('aml+riJFc• I:nl!l:rnd I)r Itctknrn, a rnctnf.cr tr/ the Amcrican ( ancef Stx:icly cnmmitlce that crtmcnrrrl a numctic:tlly I:rrgc .t:tti.tic:tl ctutly nf sm<tkirrR antl death rttct, h:tt puhltthcd acvcrnl ll:q+crt rcl:<tinpi tr+ clalittit'a) invcttiRatinnc nf Itrhaccn antl IunF c:mcer Ile h:rt taid Ihat il wic ptemiltne fn claim <rn file hatit t•f tlaictical fmttinl•c Ih:tt tnurkinf- c:rutct canct•r rd Ihc lung (:nnrrr IflrrlnRir 1'rnhlrnt, lV.rr Srnri.rirnl ('ancer, :iccortlinR /n I)r Ilcrkcnn, it hatically a hinlnpic, not a clalit- /icil, rrnhlCnt, antl the ttnlittical c<rntlutG+ne wrruld have 1n hr t't+trtrbn- r:rtcd fully by ctl+crirncntal antl tlircct t+htcrvatinrtal tludict Ix'hnc they ct+uld he c<tntiJctCtl It+ I+c etit•ntilitilly ett:thlithcd l here it, ttc taid, virtually nt+ cuhtlantiat clinical, rathtdr•1•ic <+r rrthrr dirt•t'I cvitlcntc that tm<tkinR it Ilhc t:rrr•r <+f Itnnl• tantCt Sir RtrnalJ, in :r rcccnt paml+ldct c<+nl:rinin/• Irit v;trinut Inrhlithrtl fsapCrt nnd Icctutrt tlcaling with trnrrkinp, ctrmnrcntc fxrinlcdly rm file ttalittical wnrk t+r twn Ilrrlith /nvctli)•:rltnt wh<+tc <I:rla inrlic:r/crl Ihat in h:rl:rtirm td ci)-ircltc crn<+ke :rclrr:Jly tt'cnrcd In dirrrini'h thc chancr trf Itmp cancer in Ihc I+rq+rrlitinn tturlirtl Cir ITr•n.thl, in crmnnentinl• un Ihit, hat t:rirl "lhrre it nrrthiny 1<t m V1 tlrrP Ihr+tC wh<+ t•rt•:tttv drtirc it Irnm Irclit•vin!• th:rt hmr. c:rnccr it t:rntctl ~ by trmrkinr til•.ncrt t tltry tlrrnrld :rlan hchr'vc th.0 inh:rlinp tip.rrrttc ~ vrr••tr it a I•rnrr,trr•rr In 1•rlirvr rilhcr, it, h••wrvrr, hr run Ihr ritl yd I I failing In rcc<+pnirc and, thcrclnre, failing to prevent nlhrr and m<rr- Rcnuine cauccc " •Crnti.rirnl I)nrn 'L.rRlrnlly Inrorn prtrnt' Other f.ertinent remarks on the siatisticnl studics have cnnre front I)r. Ilnrace W. N<nlnn, prnfettnr nf stalittical aeaiRn and an:dycit at the Uni- vertily of Illinnit (l+I1cRe nf ARriculture, who dctcrilxd file present dat• nn sm<tkinR and lunp, cancer at "h+Rically incompelent." I lc further wrote in a recent puhlithed communication: "I m:tke a f+ka for integrity on the part ttl Ihnce afGrminR that smokinR cantes lung cancer 1 rt their vari<+ut papers and puhlic slnlcmenls include ( I) a lrank ac- knnwledgement that any such aflirmative conclusion is a mere nl.ininn and (2) a familiar ct:mdartl of comparicnn, chrxninR tomelhing trver whit'h we h:rve, or oujiht ttr have, strme vuluntary cun/rnl, such ns the death file natn- cielcd with file use <tf the nuttnntrhile " Addilianal cihnifit'anI cummenlt have hcen made hy I)r ) Yenr- thahny, St•htxd <.f Public Ilcnllh, l)nivertily of ('nlift+rnia at Ilt•rkeley, and I)r. (•nrrnll 1~. 1'almcr, (I.S. Public Ilcallh Service's Tuberculosis PmRram, in a diccusti<m u/ file slaticlical wnrk in a recent nrticle on thc nrcth<xhrhrpy of invedigalinns of etiologic (:rcltns in chronic diteatet. l hc I:nge nunrt.cr of tmnkerc who do mN have lung cancer "•tcttify to the inarllicicncy of sm<+king as n eaute nl file diteace," they wrtste, noting Ih:rt "Ihe exiclence t+f lung cancer palienle who have never tm<rketl cle:rrly indic:rlct that cmnking it not a neceeeary came" Agrcil deal t+f retcarch rRYllt to hc done to find nut where the truth licc- if, in facl, it lice in nny of Ihe eltitlinR ennjecluret, which it very writ mny not 'I hcrc it yrnwing suRfxrrt for the point trf view that t/hc ttalic- tit:rl accrtci:rlirrn rLtintCJ hy vutionc tludict hat an cwplan:Hitro t+r cnrlana Ii<mt tlrnl ruiy tlill ntrt Le aliparcnt Imrn our pretcni knt+wlcdpic rwlf.nlnRy lhc cccontl Icli- <+f the Iri/xxl I+ath<dr+Fy- hat retlctl tra vcrv Iirnirrrl m:tlcri:rl ()n thc I+:nic of a relatively few c:nec, it w:rs cl:rirned Ih:tl Ilrc hnrr,t t+f vtutkcrt trmt:<inctl ch:uactcridic Icsitrnc, t+r tl.<dt rd tt--ltt+nrcrl littnt•. Ihat wcrc cnnatlcrctJ Irr t+c Irrcc:rnccrtrac contlili<mt In /acl, 1hc.C t(.r+1t w(YC t:rllcd "t:utinrrm.r r.t vrn•• (h-c:tliicJ eancer) - in ittt•If a cnnfutcd and tnnlr:uliclr+ry Icrrn Vrry rarly, the Stit•ntific Arlvittqy Iln;rnl Irr file Irrhacc<+ Inrlutlry Rc.circh ('r•nunittt•c y,r na•rrtl :t Inty timc tln<ly <d ifrC f.:rlhrrlnl•y <rl hum:tn Inn/•t hy 1) Ir:rrlrnr I+.rthnlr+~ittt in di/fcrcnt f+:trtt of file crrnnlry nll Ihc,r I+ithrrhr/•ittt lnunrt v.nnrut Ic.itrnt frcynrntly in Innr~t r+f nrrn tmnkrr} it wrll R 9 t• t"

at in tmt+kcrt, in f+ertnns of h.+llh acxct :rnd r+f all apcc and of di/lrrent placet of tetidenceI l hey did not believe that thetc Ictinrn were indicative and tlinpnr+dic nf iirct'ancernut crrnditirrnt ('nnflrmatirtn of Ihe need for cnntinn in interpreting such tludies came thiq year frt+m ('unninp,ham and Wintlanlcy in fnplantl In fiathnlnRic tludiet of human lung tittuea, they were unahle trt confirm fintlinpt of "car- einnma in tiru" or of an ata+eiatinn of certain nlher chanRet with the tmnk- inR hiattrry nf the ratientt. Animal F.xl+erlmrntwllon 7he third leg of the lrifxxl, aninral exrerimentatitrn, hat rrlicd rnnctly on cnnlinucd.turlret in a few lilxrratrrrict It hat hecn reported thal repeated painting nf crrmlcntatet of anrrke nn the skin of certain thaina r+f mice wat followed in tnmr nf thece animalt by overgrowth of the sk in and, arrnetime, hy c:+ncrr of thr tkin Frnrn tuch dala, il wat arRnrd fry a frw .h.1l there mipht be nrMlincct catcinnRrnic It+ people in thr tmnke ctrmtrn:alrt nnd, tlherefrrre, by inlerrnce, in thr tmr+kr of a ciP.rrtte aa cnnturned hy a tmnker On thr hmit of Ihcce animal t+aintinR c>trcrinrrnla, Il+r Ihcrrry wat pro. f.rmndrd In the effect that if the adirtt in cipireue. tmnke were teduced, the arnnunr of tkin cancrr tin mice wr+nhl lie rrrlncrtl, and the chance r+f hune+n IunR cinter wrrulJ hc tin+il:+rly rcrlntcd llrrwcvcr- an atlcrnill at quantila- live cttrarrdarinn (rrmr mitr I.r n+.u+ ur.nlrl cltcctl ctientif+i linritc 7 hr crmrinrrinp rrl-nr% ..1 /.uturr tr. rn.111r r Inn)• t:rnr rr in :+nim.tlc with dirrC'1 inh~l.rln+n t,f trt, .rrrlrr.ru.. ~rrr., I/ .rrr r~~n.nlrrrrl hv rn;rnv I.. hc rUrrr(` tipnificint th:+n alt+n p.urnrn+r• hrr.rrr.r vrr„Ir~ rt.rlf n utrlrPril :rnJ Ihr titvrr challcnPctl it lunp. rnrt skrn, rr~•nr ln :+nv cvrnr, IFhr.r rrcrrht h.+vc c:rllcrl for a re evahnurrn td the vm.kc tr,nJrnt.+tc. .kin I+ainlmp ar/'rnncnlt trn which, tip to nrrw, the whtrlc "HrirJ Icp" of anin+al ctlrctirn+nt:rtit+n hac retted. (tr.f-.tlon o/ Air rnrrnlhrn F.aretimental work hat indicaled that advertc eflet-It on hcalth may retult frnm the rorctrnce in rnan'a environment of "tmnR" or c++tnhutlir+n f+rrxlucrt of Rattdine. r+il, Raa, crt:rl, nr nther air fx+llulantt. Of ctrrrce. the cxittcnce of thcsr factntt thrct nnt rncan «icnlitlt ahtruld ditrcp:ud tt+haccn and r+ther facltrra- eithcr intcrnal or c>atcrrral - in their invrttip:+tirrnc Ilnw- ever, the f:rct 111.11 Iherc :ne trlher vnl+ectt in lunp cancer, cardirrvaccul:rr dice>tae. and r+thcr ailmcnlt fitruld crmteivahlv aflcct and nnalr/y the t+ver- intcrprclalirm with rcPard tn H+hacct+ A recent ttmly in Struth Ahira .nppr.tt air rr,llnfirrn may he invnlved in the cant:rlir.n r+l Innr cancer A rrfant f.y I)r Grrdiley flean. pnhliahrrl in rhr ID"nJr ltl.,lr,.rl /,.rnn.rl nr,tr,l rlt.rl wlrilr nrntr Srrnll+ Arric:+nt havr I long been tha heaviett cigarette tm<+kert in the world and yet they have a relalivcly low InnR cancer mortality rate. Itit study, hated on IV17-36 male lung cancer deatht in the Union of South Africa 6y age, country of birth and place nf residence, shnwed that hritiah immiprantt tu South Africa had much higher lung cancer mortality ratet than Uninn-htrrn men or immigrantt from other eounlriet. f)r. I)can .aid: "The relatively low incidence of lung cancer generally among Ihc heavy-ttnr+kinR Snuth African men, the higher and rapidly in- creatinR incidence in the growing eitiet, and the high incidence in the yrnmper age Rroull of immiRrantt from I/rilain found in the pretent study, supRccl thal the air fxtllulinn which rtccurt in mrxkrn inducUial life -- tmoke, sn,nR, traffic fumes, ete.--may he a major factor retf+nnsihle for the alarminR increaae of (unR cancer in South Africa and Ilrilain, and prctumahly eltewhrte.° 11r. Ucan'a findinRi are timilar to Ihote reported three yrart aRn hy I)r. 1)avid F. Fattcnll, nttidanl directar t,f the Natirinal Ilenllh Instilute of New 7ealand I)r. Faqcott altn frwnd that immiRranlt frnm the I/niled KinRdnrn had a higher incidence of IunR cancer Ihan native-Ixtrn l+ertnns nf the same tttrck and that diflerencet in tobacco smtrkinR did not seem to be involved ll+ere it. therefore, an nhvinut and prettinR need for invediRnlinR the Ixtccihle role of tuch air I+nllulantt in IunR cancer and other diteatet. The e><ialence of these and other sutpected factnrt juttifiet Ihe atlitude of hal- anced tcepricitm toward claims that the problem it srrlved and the inti.tence nn further retearch adopted by the Tobacco Induslry aetearch ('nrnmiltee and nthcrt rI'lic rt'.1.R.C. Rcsca rch I'r-ogram Il A Sfr rRfNrlt M.f+;.S ('erlain hatic Inincirkt influence the 1nnR range planning of the Sci- entific Advia+ry Ilnard, which it re.fxtntihle 1nr Ihe recrnnnrrnJNitrnt fha dittrihulinn of rctr~rch hmdt from Ihc T.LR (' lhcte principlet nre broad and preaurnahly admittihk by all Ihnar interetacd in adv:rncinR knnwledRe nf the eause and prevention of thtwr cnnctilutinnal or chn+nic diteatet allrihuted by arnte, nl Itatl in frarl. ttr tobacco nae I unp can( rr and cardinvatcular di[ente are :1t roretent ernt.hn%irrrl in Ihe TI R(- I'r+rpr:+m, hnt nrhrr di.cnact anrl rrtr:rrch frrrJrlrmt altn air inr lurlrrl Ir) 1 1

(':+nccr antl cardir+vaccular tlitc:+te arc Jur It+ chanFct in Ilhe cclls intl tittncc r+f IivinF f+ctqde Ift+lh cnnrmr+nly t+ctur :+flrr a Lcra+n hat livctl fnr a nunrher r+f ycart, nnr1 tr+mctimct afler a prr:rl nnmhcr 'lhere are wide and uncwplainetl in+livitlnal vari:+tir+nc am) cuacptihiliticc in Ihic respcct. ('anccr ic usually rnicrt+ct'r+i-iitally Ir+t:rl in r+ripin, i e, in a cinplc cell Carrlinvaccular rliacace cr+nnnr+nly rniprn:rtcc at a rt•cnll (+f chinpet in titcnc nr tyttrm r+f ticcvcc, i c, Ihr+ucanJt t+f millit+nc td ccllc are cimull:rncr+utly t+t cnr+rtlin:+lrly aIlrclctl '1he nririn t.f e:vch cateFnry it extretncly cr+mpres and is untlrmhlcdly dne Ir+ m rny inrlrl+t•ndenf and inlcracling t'antcc II mucl l.c rccr+pnircJ :rrnrl adrnittctl flrit t+nr knt.wlcdpc in tlhcce fichls is rn:ukcclly irnrerfcct and tle- ficicnt I Fn• mnl6lde cautrt antl inllnt•nccc nray rq~crale in rliRcrrnl dcprccc, in rhrTcrcnt nrrtcr, antl with diflcrc•nl tclalive iml+r+rlince in diRcrcnt hurn:+n intlivirlu:+lc 'f hctr pt•ncr:+l laincildct thr+uld cv+nc/antly hc ht+rne in mind by Ihncc tul+lu+rlinF rt•tr:rrth in cifhcr firl+l, by Il+t+te dr+inp and infcrl+rrtinp Ihc re tcarch, nnd hy Iht+vc infrrrminp the I+uhlic aF.nul Lrcvt•nlit+n, cautalinn, Ireahucnt r+r cure • Itecaucc r+f Ihc nurnl+cr anJ v:trirty nf Ihcce forincif.ltt, rescarch rn+- Rramt cht+uld fx• divcrcifictl in rnrlcr In atlvancc nur tntal knnwlcdp.e with Ihc Rrcalccl rsr+ccihic tf.t•cJ and h:rl:tntc Any t+nr phate trf retearch nr re• tearch al+f+n+;rth it, hy the very n:tturr rd llrc rliccaccc. IimitrJ in ilt pr+tcn- tial valuc anrl in itc appfic,ti.n, tn Ihc trd;rl Prr+hlcrn. F'A(:TORs; IN l:IN(:F:R-I: 41Ifl/l1)1 fu1//. 4R I/ICF:ACr: Ilrt+atlly cl+cakinR, t-anccr anrl t':+rrlinvaccnlir rliccacrc invt+Ivc at Icasi the fr+Ilr+winp ficldc I llrrr.filv what rflccl tlr+rt il Iravc r+n thc I+irKh<mi•.':+I and fenclic nalurr td Ilrc inJivitlu:rlr Sr+nrc inJividn:rlt in Ihr s:unc cn. virrmmcnt tkvclnp thccc di.c:rccs whilc r+thrrc drt nr+t 2. In/rr, rr.rn hrrw orut It tlr+ hmclcri:r antl lnr virutct, cithrr I+rccent tx frcvi.+ntly t•'<frrirncr+l, influcnrc t'cIl nr tistue ch:tnl•c1r I r+ wh;rt ettenl tit+ they inerca.e thc rick uf I:tter diceace? 1 Nnnirrnn - hnw mnch tL+ thc v:+rinnc nnlritive nt:rlcrinl. I,kcn, al+tr+nc~rl, cN+rcd ur ctcrrlctl hy Ihc in+lividnal aflctl ccll r+r ticcue ch:utpe-0 ( ln.leslrrrd it ++ne .ul+vlant e nnw unrler e.tencive in- vctlipatinn, hut vil:rmin rlt•lit icncicc :nnl r+thcr nnh:tl:mccc nc+y f.c iml++ntanl 1 ll.•.rrr..nr• ht+w mur Ih rl•+ thc I+rrtilrrctc rd Ilhr vari++uc I•Lrntlc r+f intcrn;il cccrclir+n. IramrnillrJ hy fl+c L+.Jv Iluirlt, :dlct I t cllv ++r li.arrt cith+r hy arn.•unt anrl r.rtr r.f a'crrti+.n nr hy +rnl•.rlnn+c' It ic krn+wn tlrrr Il.rv havc :+rn iml-nr.+nt tnl+• in lut•.r•t t:+n+cr :+n.l a+Ircn:+l d.n... 1, .~. L..rr 1•. .i. Irr..n. .r•. n+n+l+ Innl• ..u+. rr aa S. Nrrvnrrt trroin or rension-how much do thcse factnrt in- fluence thc at'livily and hmt'linn trf cells aml fianet rd varitrut sycleruc rrf the ht+tly nther Ihan the nervtws syttem ilcelf? lllcer ic rccr+fnircd at a ditcavc in which ttress ic imfxvt;mt. Slrccc it arriarenlly af.u in vrdvcd in carthuvatcular diceace. 6 l-nrirunmrnr--hnw much do phycical nr chemical cr+mpr+• nents of Ihe envirrrnmenf, intn+tlucetl as foreign nnn living aRentc, allcc'I thc ccllt tn licsnec'? Air ptdlutantt, irratliation, humidity, tent- (.craturc• tr+haccn, rx'curalional e><pt+cute >•nd I+nstihly t,lhcr faclors are rnvrdvctt in thit yuesliun. ~ Slutliet nf these fields are important in obtain a better and, evenlually, a cnnrplcle untkrclandinR of cancer causation, and all, or a majority of them, are tirnilarly to he cnnciderrd in the causalion of cardirwaccular diseate. 'Ilre 'fnlracco Induslry Recearch ('ammillee has oq+porleJ and initialetl retrarch in thete fit•h)t and will e><pand its activity nt nl+p,+rtnnily ariset r+r can Ibc crcalctl. nr:rF./.71PIN1: I.rNF:.c 7rF I7F:SF.ARf:/l In the pact, ccrtain lines of retcarch have been mentitmed Ihat seem In give prnmice t+f confrihutinr km+wlcJge essential to the umlcrtlandinR, analytis, and evenlual soluliun nf srvme or the majnr prohlcmc relaleJ lo Ihe cause and Jcvelrrhment nf Ihc cnnctitaliunal nr chronic tliscacet Thete linet r+f rect•arch include~ /. 17..n.• 1 rdFnrr 1 hc Iraininp nf fclhiwc and the dcvelnpnn•nl of tcchniyuet in in virrn cullure trf human lunlp tittuc have prncectktl satitfaclnrily al )r+hnt Il++pkins Ilrtivcrcity, the Ilrnivcr.ily rd Nchr:rtkn, the I/nivercity t+f Ictat. amI thr AIf.crt Vinstein Schrad nf Mcrlicine 'fhe dist'rtvcry by a retearcher nf nl Ieasf one entirely tynllretic cnlture mt•diurn frn mamntilian liceuc is n wckome and InnR•awailerl key that thr+uld nfa•n Ihe dnr+r trr a whr+lc new t+rder of qualitalive anrl quanlilafivc an:rll•cic t+f thr I+hrnt+mcna t+f Prnwth in MHh m+rmal and nery+laslic lisaret 2. Il i..nttnv Oictintt adv:rnct•c havt• Iw•cn madc in iniliatinp I:rrfr te:dr reccarch tleci/-nt•rl N+ prt+viJc the c:trt•lul e'r+ntrn/s eccenli•rl tt+ sut'cesdnl, tynanfil:uive clantl:ntli»tit+n nf such wirlcly ncrJ mclhralc r+f ascav at tkin painliny nr injccti+.n with v:uir+us :ycnlt Aa:rv I+y r.+lt• rd fruwth nf, ru rrat lir+nc Ir+, lransl+L+nlrJ nnrrnat antl nr+q+la.ric tt'llv :rn+l /i..uct r+f knnwn I•cnrtic n:Hrrrc in /•rnctit:rllv t•++nlrr+llyd hnclc it nlhn wcIl unJcr wav Ilhe cllt+lt d Am+wn r h:+llrnt•nn• :+t•, ntt in the snrviv•+I ..I 1•+ur r I.+nrt ++1 I'nrn.rrr. rrnn .rrt :+I... I•rin/' rnvr•hl•:+tcrl in Ilhr hnl+r th:+t rrt h.+tN:+v n+.+v I1

I+rr+ve to hc a r.f+irl, rflcctive, and cl+nvrnirnt adjtmct fit other tyla•c nf nccay ('+nnfrlrilivc rrcultc nf «•vrr.+l Ifitlr•rntl lyl+cc of :+c.:ry, wl+rn Il,r c•unc ilrnlt i . rc• ucrrl in cach, may well tlmtrihute ciKrtifit.utlly to c/ur :thihty to anrlerctind thc Ir+tal fxt+cctt of accay nlrnc cnrnplclcly, 1• Inffurnrrl of 1'..nrurrrnf nr 1'rrrf..rrr Infrrfi..n •1hc qvrcti/+n whrNher nenf+llcia m:+v r+ccur it or near OrraM r+f infcc- /irn+ hat hrcn raicrJ hy many in.cttiRalnrc r.ver n c++nciderahle f+crirrd r+f yc~rt. lhcrr are af Iract two broad fic)dt nf interett involved thil are l.rinp invettiRated both ctl+rrinlent;llly and clinically at prctcnt. A. f)r+ nrcat nf tittue, dintaprd or allercd by prcvinut infectinn, hccnnte suhject to malflmctinn nf intert'clhllar t+r inlcr-/iccuc c><- change7 ('nuW this in turn lead to chemical unhalant•e recultinR in intracellvlar chanRc or ntutatir+n hrnn a nnrntil to :1 nrnfd.lctic• lyf+e in arlj.iccnf nr tnrrnnntling fittur't It Ih• invacive apentt, tvth at non f+athr+prnic or lalrnl or (+ar tially, inaclivatrll virutet, ctitt in non ne1q+I,tUc ccllt nnd, if tr+, what caf+.city +h+ Iht•y fHncctt for Irincfnrnutirut In an active ttate within the cell Ihat Iradt t/+ ilt uncnntrrdled divisir+rl7 '+• r 1yrlll)r/lnlnllr In/f1llnrre lhere hac been a cnntirnrinp prr+wth of intcred in the ptychr.a+matic atf+cctt of tmnkinp 1he number r+f dittnctir+na >,nd puhlicalir+nt in this field hnc incrcitrd mmkcdly, at have I+I:rnc fr+r, anrl inception nf, rtew rc- tearch. 'This indic.llct that the rmtf+ut fit rccrarch and itt imrr+rlancc in t+htaininR a wcll rr-nnrlrtl I+itturc r+! Ihc cnrolinp h:+hit will prr+w lhere are and will t.c ntnny rli/ficnlliec in thc development nf thit field on the hacit r+f tlircct, nhccrvalir+nal, and eRl+crintcnfal mcthr+rh Snme fit thccc dilfrcultict will hc inherent in Ihr nalnre Id the humin material ucrd, tuch ac dre cttahlichment and maintcnancc of adcqn:+le fnl- h+w up technirlrrct tn neccstary to hmPitudinol ctudict. OIhcrt will involve careful cvaluatirm nr v3rir+ut methrklt of recc.rrlinp• am1 atsaylnR varinut 1.cychldr+Ricil or rscychc.cnntatic charactcritlicc and prra•ettet. Even now it it f4+ttihle to rcach crrlain penrril cnnclutionc on the relitinn of behavioral traits In IFIC incirlrncr, tkvelnpmrnt, nnd crtlrte nf the crmctitulirmal or chrtmic ditricct It ahnaAl be rec,llyd that it it t'hirfly in that grnup r+f ditt•atct that cert:+in atalitticiant h:rvr reported nta+r ialilln between "cxccccive" c•ip.irrrte tmr+kinR and pilhr+prnetit S. (.Inlfff 1n,f11rnrrr lhe r.rnctit- rnllrrrnrr ic r+ftcn nricrlnrlcrctrH+rl :tnrl Inicinlcrt+rrtcrl I I+r rt:+rnf,lr. il trrnra trl t.r .+ t nrrtnu+rn rrr/q h+ c tf+rt t Ih?1 Ihr prnrln ( inn.+/r ) rlr rnrnt r.r /ar t.rr ir, Il'i, r r+ml•Ir. l~rr~hlru+ wrll hr :r cin/•Ir. t Ir:vr rrt, Mrn dcli:+n pcnc fr•r ' vm•kinR.' or "nrm crnlrking"; fr+r "IunR cinccr" r+r for "no lunp t:mccr"; for "cardir+vatcul:lr tliccace° fir for "nu cardir+vaccular diccase.° I he nhcervcll hc•hivinr ttails of individualt in relation In Ihccc dis- r.ltcc prccturlc the ecictente of a simple uni-gcnic relation as hcing of prirnc in/l.rutant'e. Slatcrncntc rd Ihic kind reKrcttably have led a number of individuals to Jitcnunt rdf genetic innnence and It+te interect in the evidence of cnntplet hut nr+ncthclccc real pcnclic influcnces at wtlrk. This is, of cnurce, a tragic error in analylical Icchniyue. Studicc fit twint, at well as of various pcychtdnRical end emotional Irailc, shl+w thal there can he strong genetic firedeliclinn to certain ahililics, sk illc, and reat linnc. l heu genetic inlluences oflen diflcr in strength and in tenacity r+f rrcurrcnce and of esprettinn-even when envirnnnunlal f:rttr+rt are hchl tl+n.tan/ Intlividu:rlc may tlill tlirTer in recfa+ntc hec.utc fit their innatc charactr•ridict. 'In cnml+lic.+le rnattrrt hnlher, tlte cnvirnnmcnt, and Ihe t'h:JlrnOet thal it pretcntt tll in+l+lcrncnt or to r+l..trucl the development and c.l.rt•t. cinn fit innatc th:v:tclrricticc, ucually change radically in varirntc wayc. Icmf+l+c, intcncilicc, LCrcitlencc, and dcprce• Stm+t• prnctic rey,rm.cc tlccur with cL'vity and tlclinilcnccc when Illc cnvinlnntcrtt Lrrccntt a t•Icar anrl fi>ted ch:tllcnpt' 1 hit citu:ltinn ia, hr+wevcr. Ihc rnarkerl cu'cptir.n. Much more r+ftcn there will lie ctwnter- f.Lly and intcrplay r+f Ihc innate nnd fit the cnvirtmmcntal influences. re- cullinR in a ch:tnping, living ct+mpelitir+n. At one :lpc :utd unJer r+nc ccl ot circumslancec the innate inllucncct mny lie in c+rntrr+l, while at annthcr age and under different circunlctancet, cnvin+nntcnt:tl intluenccc m.-ty dctern+ine what nccur.. '1 here it nr+ dt+uht that differenl individualt havc difTerent inherited Icnrlcnciet trl dcvehlp a1 certain ra1et in various tictucc and nrpant lhere are ht•rcditary trnJcncicc fnr different urKant and ticaret fit ape al rlifTcrent ratct All of 1Ftic cr+n+f+lc>< internal balance and cnnnter halancc aflcctc cucc•critil+ility In l+:uh/+pcnic t'h:trlget antl ditcate. (.. SIrn7n rrr Trn.fnn I hc atrt ~. r•r Icncirrrt f:rt trn it fw•pinninl! 11+ actnrnc ru/ne in+f+r+r l:+ncc I hit I:n Ir+r :+Iqvr.rrt :+t tnuc. Ir+ hc :+ccr+ci:dc+1 with thr cnu+kinp h:+bil A1c1+• it it wcll rcc/ rnvc+l :+. .r I+rcllia/M+.inp tnrl/nr cnrHrihufnry f:nl+a Ir+ ccr t:+in rlicc:tcc• In cv:Jrratmn of Ihc cu:+in Icn.ir+n Iaclrrr, it k well to remrn+hrr Ilnl .rn.itivily I++ r++r r'I+iti .n rd clrain v:vit•c prr:rtly in inrlividnitc Sr+ rh+ rrtcn li.+n I+f Ilhr cllr+ l. +d .tr:nn :+nr1 1+1 nC+nr+l+flytinhq•ital Icaclir+n fit it I Is 1d

tn 0• i• . j r) lhe pencric maltrnp nf Ihc inrli.irlu:rl anJ thc lyl+c arnd ctrcnFlh r+( cnvirrtnmcnt.d atnnnti m c :rp:nn tl.c f:rtlrnc Ih:rl drNCrnrinc ht•Itwu+t re:rc- In+nt Ir+ Slf:rrrl, Icnclr+rl, flt/l•nt•, frn.tr:rUrrn, Inmla'Irln+n. :rml :1 twhnli hr+.t of Ihe irvnl+rmrnt prt+hternc of nnnrlcrn Irfe. lhc rate anrf amnunt uf cif+.ircttc cmt+kinp ft+lluw very ch+ccly Ihc etfr+sme of t'rrt:rin inJiviJualc anJ rry.utatirmc Ir+ cihcrlitmc invr+lvinl+ int'reacinP of rlrtrracrnR crrccc and ctr:rin I t+r ct:nni+h•, in Wrnld 1Vnr II Ihcrc wac a rn:rrkcJ rice in per caf+il:r til•arcltc tr+n.urnl+tirm hnth :rmr+ny civiliinc anJ rnrht.rty pcrtrrnncl *1 here ic cviJrnct' arfl-c.tinF Ih:rt thr vm+kinp n/ :tn inttivirhr;tl ic tlcrcr mineJ hy hic inncr rrat'tinnc ac charctl by eutrcrncly cnmplct inJ varicd Fcnrlic r.ntl envirnnnrrnt:rl f:rctr+rs In t+thcr wnrdc. Ihc cmt+kinF Ir.rhit m:ry I+c a rr/Irr rirnr of Ir.titc ralher tlr.tn n rfrtrrrnirrrr of Iht•m 'I hic carlrjrt t t1e ccrvt•c frntht•r t tl+lnr~linn l 11~1(l,vc Srt,filr.4lrt, 4n'n r 011 It will Irr rrarlrly accn Irnnt 1ht• rh•,r uccir+n of v;trit+ttc 1cluclc of In h:tct't+ and Irr:+lth tlh.tt thc cnl+iccl ic hrr+aJ ,ml the pn+hlcrnc cnmplec 11rr inrl+rrrlrr.rr fh+rnr it rlrnr nn m r rrrnulntirrn rrf nrrvrrrnrt of rirrrern- tlnnrinl or irr/rrrnrurl rfnrn it nrrr n tulrtnrurr, frrr rt/+nirnrnrnl nnrl rfinirnt rrirlrncr hntrrl.nrr dirrrl nh(rrt•nri.rn On f)cccmF+cr I?. Ihc lr+rrrnnl of rlrr Arnrrirrrrt hfrrlit'rrl Attnrinrinrt, cnntmcntinR etlitnri.illy nn'•Snnrkinp :mJ 1 nnr ( inccr,° cnitl "Nrillrrr Ihc rrty.r+ncntc nor Ihc t+phratcntc nf Ihe cnn+kinr thet+ry h,vc cullit icnt cvitlrntc In warr:rnt Ihe :rccnmpUrm ttf an :rll r+r nr+nt• authrait,uve rt+ailum " lhcre are rnany (+erct+nc, hnth intclly't•nt Lryrnrn anJ atitntict., wihrt will aRrce with that clalt•mcnt.'They will ntrt accel+l :, citnl+le cance anrl t•fTt•ct rclalinnchir in canccr anrl cnrdir+v:racnl:n rlictacc unlrcc cuch a rt•t:ttir+nchil+ can he proved f+y srnncthing mnrc than tli.rutcJ ct:Nicticc. IrancfeneJ inlcr rrclitinn frrmr anirn;rl wru/, nr lirnitctl :rtttnpcy /inJinl'c Neither will Iht•V rejt•tl a prncihlr rr+lr (rn trrl+:rttr+:rlrrnl wilh nlhcr t•nvirrrnnrcntal rtl+rrcnrr unlii cvirlcntc Iwnuifv :t Irtue cv.rlu.rtrr+n Ifrlirf. (llrlrrlrl f1y I'n.l f..lrrrir•n.r. Ihe cxl+cricntrc r+f the Lict cix ye:trc :rnrrly jndify ;tnd cul.l+r+rt Ihrtc hcticlc hcld hy tlrr Itd+:rccrr Inductry Rc•r:rrth ('rrmrniltcc iml r+titrrc I Any rr+lc of tipmeltc cnu+kint• in luunl• c:+ntrr anJ rt•rt:rin nthrr rlicricec Ir:+c nnt ht•cn I+rt+vctl nt rmrtnnvr. ? If hrlr.rttn h.ra :rny tnlr it i. nntt'rLrin nnirlcnhlrrrl. :u rl rrn in.. 1 N 1ur Ir rnrrrr rr•.rnrt Ih ia nrrrlr rl In hrllr t Inrify ;tnrt rlrlinr Ilrr I lr cipnilit':rnt I+rr+hh•mc, antl Itr Jctertninc thc hcct wny Irr liml the ancwcrc tn Iht•m 1 ,411 cviJcnt'c• int:ludmF th:tl which Jcnumctr:rtec Ilrc P.y+c anrl unicrlainticc :nrJ ct+nlrYJiclitrnc in txur knt.wlctty,c, chtrulrt hc rte scnlctl ttr /hc puhlii httnestly and (ally llre indivincirl can It+rm his nwn cuncnJcrt•d r+l+utirrn tmly un llrr hu.h u( .rnrrfrlrlr nrfrnnrrrlrr.n A Iln/nnrrd Aflirude l he l nh:rccn InJuctry 1(ccearch 'Ct+mmittce hetieves in Ihc crt•atittn and mainlcn:mce of  h:JanccJ :utiluJc ItiwarJ the ttrhacco and heallh cilualinn. It Jtrcc not hclicve tlt:rt Ihe cittr,rtinn h:tc ht•cn ctrlveJ, that Ihc prnh- Icm has Irccn lakcn carc of, and Ihal tlte :tnswcrs are kntrwn. We Jtt know Iltat Ihc prttblcmc in cancer anJ cirJiuvascnlar Jiccaccc arc Ircrncnrltnrcly cnmplic:UCJ :rnJ the chancc ttf ftndinR a cintplc ancwcr is cmall t+r non- eR1{1enl. I.ct uc Lc l+irfctlly wrr ttf wh:d we cnll cstal.liched t'iuca) I:ttlnrt, and let uc f+c huncct in r.ur cvalu:rtittn t+l whal we >1Jvtn•ate ..l Ihe tnundnctc anJ value trf eviJence---hefnrc wc altcnrfH tn ct+nvincc Ihe puhtic of :rny proven Fuill trr lack of Ruill in any widespread huntan uc:tp, ta cudr+m, whclhcr It.hact•n ncc nr cnrnclhinR clac. Whilc this illilude hac hccn crilicirctl by a ft•w ac hc•ing tnktruclive, it is actnally, frorn the InnR-limc (N+int of view nnd fnr thc ptH+J of ccience anJ hurn:mity, f:rr Irt+m hcinp cn It is ntuch hcltcr to prt+icctl nccuralcly :ntJ cltrwly ttt rcvullc thal will l:t.l. Ih:tn it ic In (+rt+icitl a•nc:rtir+n:rlly :rr.:! r:rl+iAly Irr tcnt:ruvc rnnt:luatrnc and l+atl-trullt. thal rn.ty I:rtrr havc Ir+ hr ah:rmlt+ncJ llre lt+h:tccn InJuttTy Rcccarch ('t+rnmitlce will incid nn t't+ntinnnlirm of cttncerv:rlivc, t+hjectivc, :tnJ painct:rkinr rccc:uch trn whith Ir, cct:rl+ Ii.h :rnd cxlcnJ hum:rn knnwleJhc in lihhting Ihc ctmctitnlir+n:rl ncm-accc '1 ht•cr Jivcact c:uc :rntl will I.e rn:m'c yrcal Lcacclimc cnrviv:tl I+tt+blrmt i 11

Rcsttlts of Rcscarch '1 he proRrcts tit the research fnrlRram hat hecn reflected in a cnn- tlantly Prnrwinp numhcr tit hnhlithell fahcrs th.rl nre ahc/r.rctc/l inJiviJrrally rrnd lictcd clccwherc in this Report Ncverlhelea, in order tit rrnvidc snme pcrtrcclive trf thc Rlan and «rrpK rd the prnrr:nn and tit Ihc hrctcnt statc of knnwledRc, it scemt pertinent ala. to ttnnm:rritc the finJinRa anll tech- niquet in tevcral imf+nrtant frelds or inveclipalinn At tnmc Ixrinls the tum- msries may Irnrch upon work whnse resul/s havc nr+t yet been puMithed in full Naturally, mrt all the work under w:ry nr crlm/rlctcd is diccucud hcre. 7hese sumrnaries sre: I Smuke Inhal:ttimn Studies: II 1 unR Pathnl- nRy; II1. ('arcinnpenicity and Ilinattay: IV, titcuc ('ulturr; V(->,rdinvas- cubr Rrcrarch, VI f'aychr+ f+hyaiolrrpital Stuncrt, and VII Miacrllancrnrs 1. .Smtrke InllrrGrlirrn SIrrrlie. 1 hr I I R(• hat ttir.narlrerl /r mnnlx•r erf ttnrhet in which e.lx•rimrnlil animalv wcrc rnrlnccrl Ir11tIh:rlr l rPa/rtle tulnkc Sr.ntc trr lhctc ire f;n enrruph PhrnR to inrlicalc ccrlAin finrlinR. In line ttully .cienlielt ethlree/l mice r+f twn alraint tit ciparrtte snulke inhilalilm in i m:lllunc whitIr lrrrrlrnlt Ilrc rrrllinp cnnditirmc Irr timul.rtr elnacly the mnnnt•r tit hurn:m tnrrrkinp, fra rcrinrle ai-IrrrrathinR Ihe entire nnrmal rrcar,n nf the anirnalt aftcr weininR Nn IunR cancert tit the tyhe prevalent in hum:int were fnrrduced I nnf ademrrnas tit the type thil nccur naturally in Ihcte micr r,ccurtell nm mme freyuentw than in unr><pr+ud mice Another researcher afwlicd Ihc efTect rrf srnnke inh:llalinn by (T, mice which were iltn piintctl un the akin with Ihc potent c:rrc'imrl!cn, mrthylchrd anthrene Nr+ syncrPislic cfTect was nhartved In a third atutly twn ccicntialt tcl ur thc necccairy rnichincry frrr intrrl- tlucinR frceh ciparcltc srnrrke directly intrr Ihc lunps rd drrps thrrluRh irlifit i;ll t+peninRe in their tr,chc:rt 'Ilre tnurkc w;tc rnxlucrll unJer carefnlly crm trrlllcd cnnrlitirrnc rrf RuninF vrrlrnuc, tlrn;rlirrn anJ frcrlucncy in r+rdrr trr aature Ihm Ihe cr+rn/areilirm rrf thc vnwkr wrurlrl rctenrhlc c/rracty fl.:rl rrf trnnke nrnmally inhalrll hv hnm:rrra Ihr tUuly wac trsntinncrl frv rurrrr tll;rn Ilnrc yt'art inrl im/ivirlnal rL.p( rrlclvcll .rnnkr rrf /r1 ?/I cip:rrcllc•• ll.lily frrr nriny mrlnlhc Nrr Inrnp cincrrc rlcvrlulrrl In artnlFhrr Ieluvalrlry acicnti.lt h.rvc rcc'cntlv nnrlrrl.rlrn t r.nlyct/ nrirr• Irr t i/•.rrrltc trnrrkc rnlr:rlatirrn hrr :r trrrul-whal dr/lrrcnl I+nr/urtc Il.rvm/• Inunr) Ill:rl Ihc tu,r t phhrlity rrf nrit c In Irmt• :ulrnranea rd Ilrc tNl r IIr .1 l.r.n 1•r unlu, r~I F.v I... Ir•"• rt.r nr urr Ih.rn, .l. y-,-l•. ul,~~n rb, •.rr1~IJV id nr.n nr Ithrv with trr dclcrrnine whethcr any ingredient of hd.icco, amlrkc t'an influcnce thc effective cufrldy nf thit vilamin either dircclly tit inllircclly. Anrrllrcr invcstiR:rtnr h:n dtrnc the mlrst e rtcnsivc tludy Ilrat has been sfxrn.nrt•d hy I I R('. rrn elfccft of ciRarclle smrrkc inhalalitln hy mice Crrnupt nf fem,le CF, mice were c.f+tned five lirnes a week tn Ihe snutkc frum four to six ciFarclles over a fverirxl of nearly two years. No invative carcin,rmat nf the lung were found, although sontc mice devehrl+cd a hnon- chilit. 'I he txcurrcnce of >,dcnnrms in Ihete c.fxtced animafs was ntr greater than that nnrmal to the strain without smoke etplrsure. ll. Lunlq I'aIboloRy Work in the field of lung pathology hat been nf two lyl.ca: tludics rrf hnman hrnP litsues acyuired at aulrtpty, and sludies of anim:,I Iunpc fnlhrw inl; crrnlmlleJ snulkc e.lxnure. STr/IIIF.S f/F IIIIMAN I.INVI: 7'LC.q/F.S f?arly in 14SS twelve palhnlnFictc located in hnspitalt in varirrns harlt rrf the cnunlry from clllst to enatt undertrxrk e ccwrnlinaled sludy tu deter- mine what kindt nf abnormalities occur in the lungs of human suhjectt thal cnme trt iuhlpty. The incidence of such ahnormalitics wat ta he dclcrrnincd and the relation nf the incidence to >,ge, sett, tx•cupalinn, tetir(rnce• envirnnmcnl, and eaute of rlcalh was to he dclermincd as f.r at prrttihle. Six clattificationt of cellular ennditinns were >alnpled and alx.ut 2000 N/rmps were cadlccted and e><nmined over a period of two and a h:rlf ye:+rt II was ftrund Ihat data could nnl entily he pooled I+ecause nf diRerences in Ihe classifieation tit litcue seelir.nt hy diflerent nhservera I he.e different'et were revealed hy circulating two sliJe cnlleclinns under crxle for indclx•ndcnt claaiftcatinn hy severaf pathuhopiafs. f rcliminary cr.nclusitrnt front Ihi. stNtdy were: 1'1 here w:re no aFe dilTerence in the prevalence tit clranl•ct. ctatccd :ta "hylx•rfdisia tit mclaplacia," at any ape nhrrvc 2% yr:rrc I ccs Ihan 1/1 lx•rcrnt rrf :dl catcs ttuJicd, inctudinr Lrrlh .c.ct and :rll :rprc. h:rJ mucutae cl:raecQ aI "nurmal" in :rll lire .ct lirrne Ihal wrre ccuninrlf 7 M.rlcs thlrwt•t1 chanpec deRarting flYlrm "n..crn:rl" mrrrr rdl,-n than frrn:rlca. hut htrth mrtal+lasi:r aml hylx•rlilaaia rhrl rrt cur Irc qut•nrlv in frm:rlra I Cip:rrNle amr+krr.In Ihi. ahnly femlctl tn fclvc frwcr "nrnnr.rl" crt'lirrm th;rn rtrm cmnkcrc. •1 Ilv i rrruph divitinn rd trctur:lliuna into "h~r:nrLrrrt" Ithrrtr wlrir h mx. Ir.rvr .r hi/•h r/carh r:dr Irrnn Innp t ancrr 1, Il.-r irr Inrrn in/•. :rn•I ulhrr., nrr t'nnaralrn/ cqrca rlf rncl;llrl:r.r:r r~r Irl,lvr1,t.r.r.r ;rl'lu-:rrrrl m:ulv nl rhr.c Ihrcr 1•rrrnllt Ix

I n N S StudV nf the Ix'currcntc elf rnrlaf,l:rtia nr hv(•crl+lati.r by Ihe ti7c +d lhr I:rrFrtt city in whitIt Ilrr c:rart ever rctidcd revralctl nn sipnificanl diflcrenccs. 6. Me/if+litia wa rresent rnnre frcyucntly in thntc tlyinR frnm InnR cancer than in Ihtxe who dicd from (rtl+er canccrs or rrnm III trlher cautct. 7. "('arcinnma-irr trn!' (a cl.rttificatirm Ihal h-it hrcn utrd hy snmc r:+thnl,+Kittt In detcrihe a cnnditinn thit Innkt rnicrnact+~ically like c.ntcr hrrt has nnt shown invativc grnwtlr) w•:rt rarcly diifnntrd hy any elf Ihctc 12 rathningitts, and Ihcn utn:rlly nnly when inv:rtive cancer w:rt ,la, prctent. One pathnlr,pit/ it cnntinuing a part nf Ihit ttndy by nrakinR a more minute eRaminatirm nf his collected IunRt by serial srctinn ('nndilinit of the IunRs will he con+pared in relation tn retidence rnvirnnmenl 1 he relation nf ine/aftelaia or hyperl+lasia ln cincer is unclear hrr autc elf the diflerinP cr,nt'rf,tt as tn how cancrr :Iritct in tittoe OI+ininnt rliflrr widely at to whrtl,rr tuch tnmlitiunt :+rr tn F,r (r,ntiJt•rt'rl :+t "l,rrcan crn+at'• in any trntc c1'lrl)If•:S OF Il1'lnf ll, r.trrv(:.C r f'rnm tturlirt t,f Ihe cellulir cnnrhur,n of mnnte lunpt h,llnwin` ct pnure nf Ihr rnitc Ir+ ciprerrtte Imnkc inh:rl:rtinn trnrlrr rcl:rtivcly vcll controlled cr,nrhlirmt. Icvrr:rl nnl,r rr.,nr lin•hnl•t 1,ucr rctnltr rl I Snr»r elf the nrirr rtlv"rrl I„ vn,•tr rnh:rl.1l+•,rt rlcarl,+(, hrr'n chitit ~1 c hrnnir inll:rmm.ln~n +,f thr- hnn,t lu.rl Inf,rt f Itlrrrt tlrnw no changc flum nnrrn:,l wh.rtr.rr 2 1he intirlrnce elf hrrrnthilrt rn Ihr nnrr vitrrt (•tratlv frnrn one Rrnuf+ tn enrHhrr even Ih,~ul•h thr rnrm.rlt :rre frt,m inlncd ttnckt presurneti Io he identical anrl have rrtrrved Ihc time diclt, care, ind treatment tn far at known 1'f he numlKr nf cases of hrnnchitit in any Rrnup or Ihe tcverity of the inflirnrnalir+n tccnrt to hcar no relation either to the intentity of the tmnke dt+taRe or to the length of tirne thnt the ecpoture w;rt cnntinued. 1. The hrnnchi of rnice with hrnnchitis tht+w varinnt dcRrert of hyf+crplatia and mctarilatia very timilar to that nflcn fountl in humin lungt. S. Cnntinualinn t+f the am+ke inhalalinn tlurinP thc entrre life span even nf the hrt+nchilie mice has not prnJucrd cancer. 6 When amnke e.l+nturr it rhtcr+nlinueJ m Ihe elte r+r I,rnn chilic mice. Ihr almnrmilitict (hyl+rrl+lati:rt :rmi nrclal+latiiatl trnd tn ditappear. Thetr „Ltrrv:,/innt c:+ti tlr+uht nn Ilhr inter/,rrt:trir,rn 1h:+t havr hrern nly+hr+l l,y .+une I•+Ilr„Ir,~itlt tn tinnL+r ;rl nnrrnalrlirt in h+nnnn Innrt at "1•rr1.1111rr."lt Ihr n,.,nnrr rn wlrith „nly tert:tin nritr rlrvrlol' hrnnchitis when exfaned to smoke points strongly In a di/lrrrncc in drrtr-rpnhiricy in the mice Ihcrosclves, of a nalur0 not yet ditclnted. A I"nttihlc hyl+r+thctis, which it being pursued, is that st+me uf the anim:rlt may have a latent virus infection that becomes active The e><planalinn nf Ihit phennmennn may produce some valuable leads for human studies since hurnans alsn arif.car to differ greatly in their resrCrntcs Io smoke inhalation Ilr+wcvcr, these cal.criments so far reveal no rcla/ion between brnnchilis antl cinccr elf Ihc hmg in the mice. l:nnferenre on ('Irr..nlr LunR /)i.enae. On Scplen,her 11. 1959 an informal -conference was held for dis- cutsinn of chronic lung discates at possible antecedents to carcinoma of Ih- lung The conference hroughl together hoth eaperimental scienlisls and clinicians Inr consideration of the prnhlcnt from these opMning Jirecliont of apprnach. 'Ilre slimulut nf Ihe settinn acrmt likcly to Lear fruil in Ihe farm elf new retcarch 1,1ant for allack (tn tevcral pIratet of Ihit prnhknr. Flesides memtxrs of Ihe Scientific Advisory Ilr+ard, the following were present: 1)R CYRIIS C hRI('KSON, t rolettor of ralhnlnRy, university of Tennettee, Mrmphit, 'rrnnetsee 1)R. WAI ll:k I INKE, 1)epartn,enl of McdKme, 11he (ienesrc Ilntlalal, Rtrchcttcr, New York 1)R. r111R(:IiSC I.. (;ORI)ON, I)irectnr of fducatiun, lhe love- lace hnundalion, Albuquerque, New Me.ico 1)R. IIARRY S. N. (iRP.liNl:, I'rofettor of 1•alholnRy. Yak l)ni- vertity School ol Mt•dicine. New llaven, Conneclkul 1)R. l'F('1111: 1111('IIIUNRIiR(:F.R, Senior I1inlnRisl anrl ('ytn chrmitl, ('hiltlren'f Cancer Research 1'oundatiun, Ilnttnn, Mat)achnteltt DR AVI:RIf 1. A 1.11: 1 nOW, rrnfetanr of 1'rrlhnloRy. Yale llnivrr sity Schtx.l nf Medicine. New /laven, Connecticut 1)R. BIARNIi PhARSON, Profettor of 1 alhntnpy, Wayne State llnivenily ('nllele nf Medicine. 1)etroil, MichiRan I1R. ti/1111)ON (' SOMMURS, PnlhrdoRitt, Maaathutctlt Mrmn rial I Ioy.il:dt, Notlon, Mattachutelt. 1)R. 1)()ll(31 AS 11 SI'R(1N1, 1'rn/cttor of Pathnh.Ry, ltnivrrtily uf I ennratre. M emphit, 7?nnestee 1)R AR I It1/R 1 VORWA1 O, Prufetanr and ('hairrttnn, 1)rt„rr ment r,/ InduHrial Medicine r.nd Ityltiene, W:+ynr St:rte llniver trtv ('rdleKr ot MrJit ine, Ihtrnil. Mit'hiRan 1)R k11S%/ 1 1 W WI 11 Uk, Ifirrtrnr t,f I~/w+urlrrrir., 1 I,Lrat. ('„n+munrty /1„ynt:+l, /'I,f.r.da, 1'rontytv:rni:r lll. Crrrr'inrrgrvrir'ilv rrnrl liinre..ny C/rin frnir.rin~.. K1:rnv cllr,rt. Ir:+vr f•rcn rn.,J,' hy v.rnnut invrtti~:rlnrt In drlcnnrnr, I 21

through animal ex)+eriment, whether ciRarette smoke ha• any direct cancer- producing activity. The most common type of test has contitted n( painting smoke condensates on the akins of animals, etpecir.tly mice. Widely diflerinR results have been obtained by diflerent retearchers. A few have reported cancers resulted on tkins of aome nf thrir tett mice aftet very InnR painting with high concentrations of smnke cnndcntates. Others have reported that no skin reactions occurred. One InvestiRatnr has painted Swiss mice with cigarette smoke con- densate, with and without mechanical irritation and with and without irra- diation with X-rays Some benign and malignant skin tumors were pro- duced in all Rrnups so painted regardless of coincident irritation. In Swits female and (',II male mice, inlense irradiation of  smalt, ditfant skin area increasrtl the tcnsilivity lo trnnke crmtlentatrs. 'fhe interpretation of Ihete experiments in trrms of their nvaninR for humnnt it very rtil)icnlt fnr tcveral reatnnt' (a) the mctht+dt r+f tmr+ke prntlnctinn have t,ftrn been tuch at to rai[e dr+uhtt whether Iihe chem- ical cnrnl.r+tilinn it cnmparat.le In • that of antr+ke I,rralut'rd in nmmal Ihu- man trnnkinR; (h) the rlif)erencet in [uttel+tihiGty n( mice anJ I+t•r,plc are to Frt•ol tl+at nt+yn:+nlil:rtive tr+nclu[ir+nt tan t.c drawrt ttrnn thrtc mnuae exrcrintrnI[ cr+ncrrnrny h:vartl[ (r+r m:rn frnnt tnn+ke inhal:rtit.rf• (t ) Ihc ttr+[:iRrt u[rrl irt trc:+ting ntr+u[c akint are tr+ prril Ih:tl they I+Cir nn re:tli[tit' relalinn Ir, Ihc ktnJ[ 14 [nnrlc Jr+..t~ct :+tlrctlly cncrnnttrrcrl I+y pcr+(+Ir in rvtlin:+ry [mr+kint•., :snrl (tl ) Ilrr Irrnr• h:tt an tnut lr n„+rC tllit icnt c/r:rmnt• r.ncch:rni[rnt IF,:rn Ihr akin Ilr.tl rlrr,t/ t+~rrt.rct nf trm.4c trmatrlarnt. ..ith Iht' Inng it rt•I.rlivrly hrrrf 2. Othir Afrrhorfr nt Rinn..nv. ftccau[c nr Ihr uncertainty of mnutC [kin I+.rintinr :+[ ;t Icd h,r the c:tn cer activity of a tnhalnnce, numert+n[ t+thrr methr+d[ havc hcrn et(+It+rtd Ir+r a tlnickcr• mnre rclc,t+lc• ;tnd nunr ca[ily intrrrirt•tcrl Ic[t A tc[t Ih.rl wrndd tic mcinin(-Iul in Icrm[ nf hurn:tn ctl-cricntc wr+nhl hc :t valtcrblr cr+ntrrl+n tinn nnl only in thc cr+ntirming luhattrr rc[t•:rrtlt, I+ul Inr all Ihc r+lht•r [uh- a/ancCt trr wltith /+Cnlde :nt' t'trr+[ctl in thcir rlay It+ rlev hvinlt, If• at h:,[ ht•cn arF{,cttctl, we livc in a"[ra nl tarcinr,fcnt'• it it ctrrt'ntrlv iny,rnlanl tt, lintl a way In rlctcnninc Ihr iticntitic[ inrl tlu:tnlilict td Ihrr[t' [ufrtLtnrrt Ilt:rt mey Ihave att t'tlrtt r,n la•r+(,lc I wn [, rcntialt have [cwn I+rllrt. Ir( Intb:tctt+ intr, tlrC n ccck I+r+ut hct r,f Ir.tnr[rrrt Ir+r I,n,r Lt-rir+d. t+l Iinrr 1,111 nr+ t:urtcr[ h.tvr hrrn I+rralutrrt l hc [entr rnvc.trl•.rtr+rt Ir.+vr aluAu l Ilrt' t,rl,l+rcatir+n td titr trh:+trnu[ ui.l. „f .i.i. , r.n I„ ~t,- It Ir.r I„ . n r I.,nur ,I I,y .+Iln r and their ahility to auppress these Rlands in the skins of mice. An ext.nalve study, hnwever, showed the tett to he low in power of dixrimination. Mc>rv over, the test was unreliable because some substances known to he carcino- genic gave negative results and vice versa. An eRort to rate tobacco amoke condensate by this test gave an indea number of 20 for ti•re smoke from a whole carton of cigarettes as compared to a rating of 10(10 for the weakest known carcinogenic hydrocarbon tested. On Ihis basis, ciprette smoke would be considered virtually negligible in activity in terms of this test. In another study. Spra6ue-Uawley mate rats were fed diets containing 2-acetylaminofluorene to induce precancerous changes In the liver. One Rrnup was eapnted to inhalation of cigarette smoke and another was injected with a IaM+ratnry preparation n( smoke condensale (probably abnormal in coml.nsitinn ) prepared by bnrninR cigarette tobacco in a glass funnel. llnth lubaccr, tmuke e.powres scemed tn delay tomewhat the n(,pearance n( hrccanttrrtua liver tlranRes. Similar espt•rimcnlt with a smnke (+reparalinn frnm a csrefully reRu- I:rlcd mathinC that c'In[ely dnl+lirnlct huacns tmnkinp were rnatlc hy injcclinR lhe rrrr,:rralit+n inrn, or painlinR it nn, m:Jc alhinn ratt on dictt containing either 2 arctyLnninnflunrcne or 1'-mcthyl 4 dinrcthylaminnhcn7cne. '1 his cnnJcn[:HC h:rd nn ellccl on Ihe ratc or incidcnce nf liver tumnra in ratt fcd either anhtl:rnce. Ili(/er.•nrrr in .Snruke (:nndrn.nr.•a I hCtc fintlirnFt cmph;r[iac lhc ditlcrcnt't•t in varinn[ tmt+ke cnndcn• [:ttcc ;md illuttralc the nccc[tity nf u[inR smnke prndut'ctl undcr nnrmal ctrntlitinnt. Othcr invcttiF:rtnrt havc tturlicd the (vrtt[it,lc cn c:ncinngt•nic t•I)t•t It nf nilrnr.Cnnns ct,nrivnuntlt frnm tuh;rrcn (in ( t) Ihc incitlCntc of ttinn I:rncr,ut rulnn,nary adcnnnrat in Slrain A mice, (2) nn urelhane imtncrd I,nlmr+n:ny atlcnt+rna[ in Slrain A mite, (l) nn X•ray indrttt•d lyrnl+hnncrt in ('S7 hlatk mice, nnd (4) nn tdlravinlet (iFhl induce•d tkin ttnnnrt in Swi[t nritc Nrt arth cflcclt were fnund. l7rrv havc fnrrntl that injcctinn nf fincly tlividrJ carhnn pnrlirlrt inlr, thC hlra+J[lrcant will rtrcally increate Ihe numhcr nf Innr, lumnrt Iltat n.+rnr.tllv tMtnr in Srr:rin A mitc A nculral fractir+n nf t,d+atcn amr,kt• :rd [nrhrJ on [uth c:,rhnn I+:trliclCt trlnre injcclinn tlit-h/ly drrrrntnl Ihc nnm hrr of lumrrrt lanrlutrd I+y IhC carf.nn It w:n :rl,r+ Irrnntl Ih:tl a niarin tleficit•nt dicl in Srr:,in A ntite will frrally int rt.r.r- Ihc intiJcnct' of [I.r,ntant•r+ut IunR n1lr/+nr11:1t, wltrrr.lt :+ vrl+/+/rmrnt r+l ni:a in [crvn[ In I+t• I+rrdrelive I rrvtinr. 1 I+yrirtyl nrr•thvl Arb.nr, :,n r•.+L,ri n/+rr,+lutl nf nitnlinc 111.11 cr+ntt'ivaldv t"trlJ :trt :+t :t ni.+t in :,nlnuct.rbr~lrtcl a1+1+c:vcA tu :+Iltvi:tfr• IhC ni:trin tlcliticnr v:tnd dr

I crcice thc Innu+t int'irlcnce 1 Irr ~r+aal~Ic :It tinn (if whi+lc inhalr l smc+ke as in inri ni:rtin aprnt is nuw unrlcr .Imly Anuthcr acirnfial hat e.Fh+red acvcril mrlhnJ% that mighl Jrveh+F inlrl nu•lol hir+:rccay Itthniynrt frrr mc:tanrinp, carcim+Fcnicity llsinp a suhculinrmn airhnnth for Inrnrrr Irinapl.rntatn+n, hc has mca.meJ the effecte c+( Inr+wn c:+rcinr+Rrnie aRenfa in enhanrinR trr inhihitinp• Frrlwlh. fohiccrl amr+kr c(mJrnsates sn far emphrye(1 have ahr+wn no actit+n Smme c•nnrplicatirms hivt• dcvcltq.ed in the np(+licntitin nf the metht+(I and il hat nul yet cvr+lvrrl rntr+ a whnlly talit/aclrny ted rrr+t'etlure •I hr Utrrine crrvu nf nltCe hai been uaed as a lesl tisaue (nr rlclermininR the r+t)tency t+f apenla susf.c•ctetl (if tx•inO earcinnpenic. lhit tisa/e re- semhles lunR lissue more closely thin dr+es Ihe skin (•iRareue arnnke cnn- dcnta/es were applied In the eervix and uFl.er vaginal area td mnrr than 21m) UI/A I mite r+vcr a I+critwl of many mt+nth.. ('nnlrrdt receivetl a+lvrnt alr+nc, mrthylch +l~nthrrnc in the same at+lve•nt, t+r twahhinR with A dry cnlltrn Iil+l+er1 al+f+lic:rlr+r l hcar nlit'e f+rr+vrJ a+ Le trir srnailive In firnrhlce a valid /cat sintt• Ihr trdvent al(mr rt tht• dry afydicatrrr rraullctl in r»rne tumnra Ih.~n diJ Ihr alqdicati(+n nf 111, anu+kc crmdrncalcs In view r,f theae resulls, it has been necrsaary nf cnurte trl :Ih:tnrA+n Ihis rnelhntl as a valid tt•ct While t+thers have crrnsidererl sipnifieant the intluctir+n nf tumnrs at this cilr with smr+ke ci+ndencatcs, thc hi{•Jrer incidence (rf /umtrr induclicm with a pI:rin arplic1trrr in Ilric wrrrk raiacs scrinot dr+uht as Ir+ the validity t+f any such cunclutirrns ('nrrln.rRinr.i. In r.ynrph•1.ar .Inlnrnfa (i>ttensive studics have been maile erl carcutn~enesis in ducks and chickens by mcrhylchnlanthrene api+licrl In variuus tissncs •1 fre resl+rmaes of animalt eq ripl.c•J with !c alhrrt insleatl trf fur anrl IackinR lyrnl+h rlanrl% were ctmsidcred wl+rth tlnclyinR frrr ct+nlr:rst willt Ihe mtxe f1rniliar re- tF(+nsrs t+f marnrn:rliin sFeeica M:/ny inlereslinp nhservalitrns nn tht in duclinn t.f tunrnrt and on their behavior have hcen rcrnrJed Mt,d rele- vanf perhiFs is the cnntrasl in aclir+n r+f rnethylch(danlhrene inlrtnlutrl intn lltc Iracht•i in I+canut t,il sr+lulinn :tnd that tlf li+hacct+ srnrrke cmnrlcn aatet intrrrtlute(I in Ihe t:lme vchicle -lhe nrrlhylchr+l:mthrenc qirickly lantlucra :t very inlt•nae in(limm:rti+m whilc Ihe tir:rrctle vn +kr ic I+rac fit:rlly withoul r/frcl Another invralip~tnr i. ttnrlyinr al ll :rnr+lhrr I+hrnnmcnrm that aly+r:rrc Prnmicinl• :+. .1 I+t.ia fi+r a Ir.l ncll+0 11(• L:r% r~harrvcil Ihnl trtteirt Irnnrua whi+h r.innnt nrrlinerily F.c Ir.m.ld.rnlcd Irr a atrain nf mi,r in whirh Ihcv u' .ilirn wi1) "t:rlc•• an.1/•rnw i/ thr :mim:+lc :u,• fir•t t+nm/r,l (ni fr.l1 w.ih 1 m hy~hn~:+rl.nna lur :r Ivri.nl n/ Innc I+n.•r In Ilhr ?I i Ir:Inal+l.rrV I hc time tlurinR which fhe trancldant will Frtlw is tclalcd In tlre dr+a:r~r r•f hythr+catlHrn given Wilh cullitient drr.apc, evcn nnrmal skin (trnn Ihc :rlicn str:lin can he Iransl.lanted suct'ctdully fur rcrintls rcLtlyd lu thc lh+a:rl-e 1 his nlcthtKl apl+c:us Itl be wcll suitcd Itr quanlilatiun and its evahctlinn fly ctnnpariam r+f a large ctdlet-titm nf Iv+lynuclc:n hydrn- cathtms is undcr way- One scirntial his undertiken to Ruide fnrlher sludy (+f a carcinn- Fcnit'ity ataay IIIrI111NI h:Itetl trn Ihc rcallrunc nr a pttdt.rrran (I'rnumrrrlrrn rr+rJunrnr)l Irr ullr:rvitdel light frdluwinR ealxnure in Ihe tlark lu a prrly- nnclear Irydrtcarlarn. •Ihe resrt)nte is reputed Itl he related Itu carcinogenic :rctivity (+f Ihe hydrtrcarhem. Cnrnfiarison tlf a large numher of such hydru carbnns is to be made in parallel with IPtts by the mclhtrd deu-rifred in the preceding paragraph. rrrnna.ny Cnnf.rpnre A ctmference waa held St•rtemher 10, I9t9 for discussitrn of car- cint+p,enesis and hir+issay methnde ('ritical an:tlytit was matle trf hilhrrln Frevalcnt mt•Ihtala and nf recent dutlics supFcatin(; new al+lnr+athes to Ihe prtrblen,. '1 he discnnsion retulletl in the planning td several new cn t+rdinalctl siurlics to compare the resullt nf different ntaay Ieclmiques. fletides mcnthers of the Ilt.ard, tlrc following were presenl: 1)R. R S. 11F('KF••R, A.u+ciade Prnleasnr of ('hemiury. Ilniver.ily nf I lnutam, I lotrston, 7 eaas I)R. R K. II(/111WF11•, l4.arciale 1'nde.aur of Oncoh+Ky, llniver- aily nf Wiscnn.in Medical Schnr.l, Madhnn, Wiac•nnain 1)R. (7IlISFPPr°. 1)Fl.1,A PORTA, 1)ivisinn of Oncoia{ty, Ihe ('Ihi eaRo Medical Sehonl, ('hicaRn, Illinais hR. I(11115 h. rIr-CUR. Prntesan cd ('hemiUry, Ilarvard Itniver sily, ('amhridRr• Mas.achuactts 1)R. I RF1)1)Y 11OMIIUk(iI R, PreaJent, Nio Reartrch Inuiwtr, Inc , ('amhridRe, Mas.achuaus 1)R. A W IIURION, Aa.nciatt• Prnfestnr of Indu.rri:rl Itralth, lluiver.ily of ('incinnari ('tdlege of MeAicine, ('incinnali, (Ihir. I/R. MnItRI('IS LANI)Y, llcad, 1'ntyaacchariJc Scctinn, I al.nratr+ry r+( ('hcntical I'harmacnluRy, Natinnal (-ancrr bnrnute• Ilrrlrr. la, hlaryland 1)R MI I VIN S Nf'WMAN. 1'rofet.nr r+f ('hemiury, Ohin Clac l /nivrraity, ( r.lumlac., (/hin 1/R. Wlt I InAI 1~. 1•/)1 1, kr.rartlr At.rai.rtr in ('h•uPr, 1:,b,+r:rrr.ry (r+r I%t+rronenlnl ('.rrcimq•rnrait, Ilnivcranv r•( 1'dlabnnrh (:radu.itr titluN+l u/ I'rJ.lrc Ilrallh, Purahurrlr, P,•on.)Iv.,ni.r 11R FtI NIAMIN A NIIIIIN, naar.l:nd 1'r,dct.r+r rd I{•idrrni.d,41y, Il:rylor Ilnivrraly ('ulk{tr nl Mrvlirrnr, Ih+minn, /r.aa 1)R LII/KR,1Y ) 5111'AR, ( hirf, 1 nl,.nrlnry t+f ! hrorir.J 1'h.um,r tnb•Ry. N.+tn+nal (.rntrr Inalilnlr, llrthrart., M.uylnn,l MI\\ /(/nN %Afllll, (Rc{+rra- r•rin{• Ilr 1/t/ Cninrl,•ur. If•t+.i1 rnrnl of 7rwrtuRy. Indi.na llnivctvty, IIln,rminRl,+n, InJh•m.1l 25

I)R t'AtII 1? S11'IN1:1(, 1•athnlnri.t, 1hr tna,rutr fnt ('aatcr Rr- tr.irch• I'hd:rdrll,lri:r• 1'rru,cylv.u,/.r lyR (' S Slll'l1ANt1, 1lircttnr r.l krct3rth• Strl,h.rnn I+rr,ll,rr.• Inc, I'hilaJcll•hi., 1'rnncylvanis 1)R IOIIN (' S/I RII• Acanrrar 1'rnfct.r,r t,f 1'h~rmscolntY. 11~1 hnu.ir llni.rrtrty, Il.rhla, Nov.+ Ccutia f 1', Ti..rrr (:rrlllrrr In Ihr hnl,c Ihat Ihc olncrvatinn nf hurn:rn lunf lictne Frnwn i.n t•itr.r nnrl ttudy nf itt rc.pnntct tn carcinnFrnic and t,thcr aFcnts ntight prnvidc ncw nntlcrtlandinR tit thc nilure nf catcinr+fcnccic, thc cullure (it cuch tit- au hat hccn undcrlaktn. (iranlc have hcrn maJc ttt hnrr lahnrnlnricc h,r ( I ) traininp, f,crsnnncl in this kind of wr,rk, 12) :NtctnrlinR tn c•lahliah sttaina nf v:,tit+us httman liscuet, csficcially Innr, tic.uct, I 1) rrt+ccrvinR Ihc n:rtnrr nr t hanpct Itnrn nnrn+al h+ matirn.,nl tr1h, and (d) t+hsctvinp :,ntl tksctif.inr Ihc trct,t,nact nr tuth littnc lu Inl•:utrr crnr•1C inkrcJicnlc and tHhcr aFcnlt 1'. ('rtrrGrrrrr.Prrlrrr IT.•.errr.-h lhc Scicntrfic A,Ivicmy Itr,.url h.rc t•,nlinuctl ilt :rclivc ittlCrcct in thc ficld r,( c:rfthr,c:rttnl.rr rrcc:,rtlr wr11r ./,cti:rl It•fctrnt'c 1r+ 1hC c(Ictt td nicntinc antl tnn,krnr ,n tht• tirtnL,linn /(r.c:trch )'r:rnlc h:rvc hccn tn:rtlc hy IhC 1 1 I2 I lr, cnl,l,nrl wr.r1 rn 1b tcrtlt'r, t.mtcrnrrt wHh c.trtlir,vacculat rhycitdt,Cy antl ttc rlnr•rtlcr. lThc I'M Rclnnt r•t Ihc NciCruriit I/rlCtb,r cont.rinctl tlratil,+ita+c r+/ lltc «'ttf.t tttul, vthc-n 1c:trl.rblt•• thc rc.nltc nf tnany ((ojctlc cnlq•ntlctl hy Ilht• 1 I 11 (' Sincc Ihcn, a nnnrhrr tit (,ul,tit :rlrntnc havc :+~) r.trrtl in Iht ct icntilit (itcrltntc :tml atc ~h.tr.,ctctl in Ihrc I(cl+.•rl G,mc tlc:rl wrth h:r.ic rr.•l,lr rnc in c:trdinv:rccnl.rr I•hy•ir•h•Ry whilc rrlhcrc art• tnntcrnc,l with tlran)•t•c in thucd hy nicntine :+ntl Ihe snnrkin}1 of ciF_:ucttCc In view tit Ihc cl,ctul:Hnrn :rhtnrl Frt'.rvy cnn,kinp onrl dc:tth. (1r,m ttx,+n-.1ty diccacc, :t 1•rit-1 rcvicw t,t ccitlt-ntC• rclolmC tn thc Cllr•cl nf nrc"tmt• anrl vnt,kinp, nn Ihr cnrr,n:rry t ircnl.rti..n :tnt1 h:tccrl r.n Ihc rccnltc rr 1„+rtcrl hy I I R(' €tanlct•c, nt,)thl t.e •4 yctial intert•tl hiJjrrrnorr. In Rr.pnn.r Sincc tnn,Arnl' .,r Ihc rnlrttr.,n .,f nur,linc rrn,uu„nly rt-tinlt. tit :+ rc tlrrt/ir,n in Ihr cnl,t•tti,i:+1 tittnt.,In•n• .+\ i+r,lit'.rlrrl I,y Llrlhyat,,.•)•r:rl.lut nrr:rtnrcrnt'nlc r,l thr h.rnr) „I hy :r f.rll m.kin Icml., r:tlruc. ment h.rvt• cnntirlcrrvl nit,qrn, t„ l•t• :r )'t n, r.r1 v:+vn „n.Intl„r .tp, nt I l,t. „vrrl,,,,k. Iht• 1_rtl Ih.rl Ihrrr• .,rr /•rr.,l rlrlicrcrnr. in rh.• rc•.)•,•n,c .,1 ,hl)crrnt v,"r ul.rr I.r,lc t,. rn.,ny r I,rnut nl .,)•rn1\ It h.r. 1,.n)• In rn knnv.n Il,nl 11„~rc i•, a tc, tt• rt,t-:tl :tc'tirrn I,ctwccn Ihe vatnnutlt.t lnnt tit Ihc dt•cp and arrcificial vee- sclc '1 hat is, whcn Ihcre is cnnslriclion in one arca, at durinR aneslhttia tit atpltyxia. Ihcrc is dilat;clit+n in tht olhct. This rerttttn(h tin asfxct tit hnmrr,tl:rrir rr);nl,lir+n Ihrnuhh which the total f.eriphtral resiHanct .nJ thc copacily ttf tlte v:tscular syslent rcnmain ct,n.tant 'I hus Ihc cirtliac nutput antl l+ltw+tl presnnc m;ty hc liltlt aRcclctl in the fact nf rclativcly IarRr tltangcs in pctil.hct:rl tcai.t:nxt nr tht+.c ntikinatinR in citl,cr thc dccp nr tnf.crfrt•ial va..cul:rlurc( lltcrt is qcncr:tl aRretmcnl Ihat, in the knlatcd htart, nicntint added Irr tht pt•rfucinp, tncdiurn resulls in clilnlation nf the cnrnn:vy arlerict I Ittw- evcr, it w;tc nt+t ju.ti/icd tt+ aaunrc ftrun this td,urvalit.n that anth is thc c:r.r in Ihc inl:+cl :rnirn:tl, since nicr+/int allt•cts rtlhcr cltut'lurcc that ntay ccctrnttatily inllucncc ta+c ctat+naty hltw+tl flt+w. 'Ihut the ctlcclt +,f t),inc• hhrinc t.n Ihc t ircul:rlit+n rcccntl.le in m:roy rccfut'tt Ihtnc of nictdint•, and sintc nict.tinC .tituol;+tc. thc atlht•n:tl Incdulla, it it I+rt.hahlc Ih:d thc cf,inc Idrrinc rrlc:tcctl ctmuil,utcs trr Iht eh:rngrt t+h.crved 'I hcrc it a faitly extcncive lilttalutc tin Iht tffcct tit smttkinR on 1ht crat+nnry cirtul:rlit+n Much t+f Ihe wt+rk turn whii h Ihis is hatcd is nnl I,rtq,c•rly ctrnUtdlctl :unl ncctl ntH l.c dcccrih(•tl hcrt:. Ilnwtvcr, tctcnt ahnlicc in hr+llh m.rn and r+lhct m:rmm:dc Ic;rvc nt+ dt+uht that nictdine hnA (-Ir:Irfllr cnn+kc tcarlt in an int rc;t.c in ct+ttrn.+ry hht.+d llnw '1 he siFni/icancc ++f 11hik nt•t•da Inrtht'r cnnciJt•t:rtinn cincc Ihcrt• is ;rlstt an int'rcacc in hc:rrl r:rlt• :rnJ in thc ft,tcc trf t t+nttat tir.n duc, :tt Iratt in patt. In a dircct atclit+n r+f nir++tint ++n ittlr:K:rrdiac •frtrcltlret In vicw n( thc f:trl Ihat nictttinc inctcacts cattli:,c wt+tlk, 1hc Iprcclit+n :Irict•c ac In wht-Ihcr, undcr Ihc.c circnrnttancct, Ihc cirt:ul:rlitrn kcCpt pacc wilh tile ntcl,ltidic tcyttitcntcrHs td the htarl. In dt+Ps, intr:lvrtlnl/t Infntlt,nl td rticrrtinc aml tlirccl injcctinn intrt Ihc crtrrmiry :utcrics recullctl in e dc/inilc inctcasc in ct+trmary flow. In thctt c%i.crirnt•nts thcrc w:rt a t-nr- rc.l•rrntlin(• int rc:tcc in cattli:rc wtnk, hnl hccaucc in cnme inct:rncct Ihcrc wcrc ch;tnyt-t in thc A VlnxyFen tliftCrcncc :+ntl invrrcir.n trf thc •1' wavr. thcrt m:ry h:tvc kbrt•n tnmc inrcrfrrcnct willr Ihc ulili~:rtiun nf t,tvrcn a r++ittt +Ic~crvint• „f (rtrtlhcr alttcly. f urnlrlr. (. ri..n ..f /yl.ulinr 1hc tlcrc.tr,.n r.l I.I:nlit;+1 crnnrrn ic lltc c(1t•t1 tit cmnS,inl. r.n tort.n:+rv 16,.v in rnr.rn 11,r :u lu,nc rrf nir nUnc :rrc cr.ml,lrt nn.l int lrn)t ttinur Lrtir.n tit tlrl+r..•.r,.n nl v.+rir.nc 1..a1% r,t thc nt-tvr,ns cyslt•nt :+mt Ltvil.lhcr:rl tlrtn I,nt t cur h.r. th, mn.r Ir. :rn.l )•Lrn.lt I lt'nt C, rt it iru/,nrlnnl t,. .Ir Ir rrnmc whel 1r rly.r n•. In Ilhc t nt..n.nv t irt+rl.+lir,n nnrlt-t nnn+,.rl i r.mlrtrnn. r.f cnrnf<in)• I tl•rrirnrnl. h.rcc hccn c:rrrictl r•trl n/iliiinh Ihc Icrlurirlnc r,f T .r 2) ~

inccrting a calhcler Jnectly in/n the coron:lry cinus lhe dala nhleined ahnwed 1th.r1 amokinR resuhs in n aignificant increaae in the cr+rnnary hlrx.d f6rw and a siRnifit'ant declinc in Ihe crnrmary vascular reciclance. 'Ihete wac a fall in myocardial nsygrn e tlraclitrn, hnt since thia was prnror'innal Irr the rice in cortrnary hlrrrHl fkrw, it wnt concluded that the r+tygcn con- snmrlirrn wat not .ignificanfly changetl 'Tlhc rxfrriments jvst menlioned are in accord with the r.hcervalion that rlcctrocartliographic or hatlislocardioRraphic changes are not se!n in healthy individuals aa a retull rrf smnking. Ilowever, when the coronary arlcrict Rre discacrd, tmokinR commrrnly prnchrcec ch:,nges in the electro- cardiogram charnctericlic of anoxia, and Ihis has been employed at a lest of coronary funclinn lhere is aho the fact that in an cccaaicrnal patient with anRina peclnris an attack of pain may he precipitated hy cmoking or c.thrr activitirt I hrac nlncrvatinna cugResl th.l Ihe elleclt of .mrrking rrn the diarase hratt may md always he the aame in heilth and This is an irnh-ntanl frrr+hlcm for furlher invesligatian Sinrr tome ri.k miy Lr invrdvcol in cnr li:/c cathrleriyalirrn in the iarccncc (if crmonaty diaeacr, nther Icchniyues for Ihe mcacnremenl of hlocrcl flnw arc under sludy In Ihe rncanwhile a ctart hns been matle rm laboratory studies in which the rffcc/c (if nicntinc h.ve hern tected in rahhitt rnatle athero- cclerntic F.v hipJr cholralrrrrl tlirls 11 hat been rerv<atcd that in the mamal hcart, i+crfucirrn with nicr+tinc rranltrd in a brief drereacc in coroniry flow that gave way to a more rirr+ttinprd incrcice in the ratc (if flow fhe lattrr phaae, refireccnting a rlilatation r+f the cinr+nary arlrrirs, wis ahccnl in the atlhrrocc'krotic hearl In another dnrly of rahfhifc main/ainecl on 'a high chnlcctcrnl dirl, the oral nclministntion od nicoline rlid mot aRecl the Irrum cholrctrrvrl and phrrchhnlirii(l valuca (if the tlcr-.rrc of arrrtic alhcrtrcclrnrait, hul d 1 rranll in an incrciscd mrrrtalily and incrrased incidence (if fiilhnic.pic,l ch:rnPcc iii the hcirl and reriphrril vascnlatnre Similar exrvetimenlc in chickens, hut with IarFrr rhnes (if nicrrlinc. pnwluced nit significant carrlinvascular l.athtrh+pic changca ovcr Ihrrcc rrcnlling from the hiph chnlrctrr<rl dicl ;rhmc. '1 hc rrculls of hnthrr aluJira :rhmg thcac lincc arc nwaitrd with ai ct ial inleresl ('.nrfinr•n.rrrfnr ('..nl/rrnr• (irI ntrca nnJ r~11,-r a<irnti.I( di6 nr rru:rrrIr in Ihr t.rrrhn1•.r.rut:rr f rhl ntrt /r-r :r r-nrr, lditcu..i-n I nr I J 1'/1'/ In .~ I lili n In n rrirl' rra 1.1 Ihr ccirnllfsr nIl% i.my It,~:rr,) Ihr f~dL~winp wrrr fnr.rnt IIIt 1 Itr~t',t rr A t Iltlr,l It n, 'a-, ( nv /t. .1 Il".r... I •.1.. • . I 1)R KI/R I 1)i'. ('R1NIS, Grddwaler Mrmorial Ilnapilal, Welfare IJand, New Ynrk, N.Y. hR. f'RANK W. 1)AVIS, lR., lohnt liolrkint Univertily Schrxd of MeJicinr, H:Jlimore, Maryland. IMrml,rr, ('ommiltre on SmokinR io Relation to ('ardinvatcutar 1litraae, Amrric.n /lrarl Aauciatiun) 1)R 111OA1AS R I)AWIIF.R, National Ilearl Intlilule, flcthr.da. MarylanJ (Mrmher, ('ommit(ee on SmcdtinR in Relali.rn to ('ardiovaacular 1)iseatc, Amcrkan Ilear/ Aasnciation) DR. /A('K I RI.UNI), Medical ('..IIrRe of VirRinia, RichmonA. Virginia UR. 1Ah11 S GII I fTTfi, I at+Mrralory of C'hemical Pharmacology, Narional Ileart Inslilule, 1lelhcada, Maryland 1)R IIARVIiY 11. /IAA(D, Medical College of Virginia. Richmond, V irRinia 1)R. PAU1. S I.ARSON, Medicll ('o1kRe of VirRinia, Richmnnd, Virginia 1)R. ANI(1NIU fyE 11'ON, PhiladelPhia General Ihxpilal, Phila. drlPlria, Pcnntylvania OR KI•t I.Y I McKF.E., Merlical ('ol/eRe of Snulh ('arnlinn. ('har Irclr.n, Grolh ('arolina 1)R /11 RIII RI MtKI?NNIS, Medkal College of VirRinia. Rich mond, VirRinia DR. I:.I)WARI1 W. PFI IKAN. Rotlnn l/nivertily Schnnl of Mrdi cinr, Itnttnn. MaacacAn.etlt DR. WAL I FR RF.UISCII, New York University--Rcllevue Mrdical ('entrr, New York, N Y. 1)R. SFYMOUR It. RIN-7.I FR, ('ornell lJniveraily Medical ('ollrRr, New Yrnk, N.Y. I)R. l1 RKY f. S(.'IIMII-IIII?NNI:R, l.ankenau Medical HuildinR, Phila.lrlphia, Pcnntylvania hR. ('AROI INF H11>F11. IIIOMAS, lnhnc Flopkins Univrnily Schnrd of Medicine, llahimnre, Maryland hR. lAN1 1' IRAVI:I I., (brnell Univertity Medical ('nikRe, New Yrnk, N.Y. I)R. 1)IIANF . (i WFN71'.1 , llniveraily of Kan.as, I nwrrncr, Kanaas I)R. 1. F1)WIN WOOI). Medical ('ol/rRe of GrnrRia, AuRucla, (irmria I'l, I'.yr/to-phyaiol-roRirnl Slri(1ir+ 1)uring the course of the pasl year several new sludies were inaug,ir- rated in the fic6k of psychrdoRy or of ptychrr-pllysioh,Ry. Onc un,lcrl:tkinp is lo ctudy smokinR practicea nf yrrung coIlrFe dudrnls in rcl:ltinn Irr C:unily hislnry, type nf secnndary t'hr>,dinr, ac:rrlcmic inter eala, :It'n/tl'/lllf :Il hlfvrrnNlt, an1l tnrlal relal/11n{hil+t. Aeurthrr rrmrlr ic e+ldnring 11rr la•havinral rlfcelt rrf arnokinp unJrr atrcas conAiU -n. Irr drtrnuinr whclhrr aurll c/1ct'Ic nrt' trnryr,tr.tl.lr I, thw'r rrf rranilnilr7rnr. Aro/•a Iln,ly m.n1.Fh.. l.-l-y (n rrLrli"m t'r tirh:trtn u.r i: nrtw Ihr ar,hirrl nf .r al+t'cial invrcli/-aU"m 7y

rr, tn C> fJ A)tilnl alutlv rll cnnikinp h.lhitt annlnp f.lllcr pcrtnnt ic 1,rinp. nt:ltlc Ithtrnl/-lh Iht' Al-i ( t'nlcr tlf Ncw 1 nl•I;tn.l r rr. nri..-r•rrr)tlt•rrtt. rinQ nn thc cancct prt/hlcm irc onnmiri>'rd hcre. Scvcral alutlirt hc- Unr tcirnlict hat I~crn invcdip•,linr Ihc ctftrarr ftf varinua tracc mrtalc in ht+man hmpa and li\cts in «arch td ptlstihlc cluct to the rrcvilcncc of p:trticular diccicca in cerliin Incalilics. I urlhcr invcctiFmtnn hat hecn tnadc (tf how carcinnFcnic arn flycs arr incnr(+nralrtf into crrlain protein cnnaiiluentt of the liver. A scicnlicl hm ntidc a hacic tt+nly n( tl+e mechanicm nf hvf+c'rrlacia and retiatincc Ilr hac chtlwn how irrilminn will ftrcl prndnce protein dcrlrlinn f+1 a lictnt• ac rcflcclctl in citculatit.n nf ccllnlar rt<+tcint at pttlhu- lirlc in Ihe ccrtun, Ihrn increaced rratlanCr to fnrlhcr tlirnipr. Ac rccict:•ntr inrre tccc• t11e irtiti.tl hvl+crpl.talic rrtl+,+ntr faNc tdl cha+l+ly antl Il.e tc citt.tnl akin Itltcc ill hyl+rrf+l,tcia "kin rr\I+ttntft ill tflhatcn cnntltr rtlnctt a it rlr,rt In nlhcr nprntc /k hacic ctully wav mitlc frf Ilu ttnthnlnpy of human t+ral licalrt, rc rrci.dTy ic trl.llcrl Ift ,pinp (1h1 Chrlt X t.ly (+Ilt(-t t.f f,rttr+nt Mhn wrrr rvrfltll.llly (I6pn"tcrl 1% havinp Illnp c:lnt rr wrrr tlnrlirtl 1}tc tn.tin rtlrf•r,ct• waa tn imj•tt+ve Ihe intctf+r{t;llil•n t,f llrr t'.IrIu.1 , 1. rlllr t.Irlrrar,r rJ hrnl• r.rm f'r :1• rl rr.llcil hy ritliulnpy At I hy (,r-hli I r•1 It- .lu•1, .vl nn I1\tr+ wat tn:trlr r,( Ihr IYctltfl;ltirlnt trf tl1(' 1+rfl/+f1[ t\ll.~ll' Irr•1.•Iri +\\l /r' r r`Ilrr Ir'rl I I11• l/rr.Nrrl th'il pcrtunt whrltc rr t nl+.lrwn. tnhlrt tr,l Ilirrrl t„ nltl.rlnlinn 1,/ rluvc im1 fUtnet wetc nmtc IiLclv 11+ t+r hr:l\v tttt,•krl. llt.tn t•t'relmc nol vl c.lrrr.rrl AnilVlic.il atutlicc wcrr rn:1Jc ill crrnllt:trc Illc Lratra ill rfdynntlrar llyflrt+cnrlrfrnt in mainthcartt nnll aVtlrt}fcanl tmt+kc f+tt+tfncctl nntlrr v:uinua crtnttilinnt lhc e1TccIc of tmnke nn Ihr ciliary :tctivily ~rttl Inut'flut flnw in ianlatrtl hrr+nclti ill crvcral animal tl•ccict :tlct+ were t+l.ccrvcct Frlfnrr.frff. Prr+Rrnm lhe rnrtlical aturlrnf fclhtwthip prnptam, tttirin:tlctl in IQSS ttf+nn rrcrrrnmrndalinn nf thr Scirntific Arlvia+ty ISn:tn1 anrl tcncwccl cach ycat tincr, ctlnlinucd In chnw enctrurapinp rrcnltt in I')Sr/ 1 he lirnpram it tlrtiprtctl It, tlimniatr intrrc\I in t.:ttii rcacmt FI amr. nr nlrrlu:tl tchr+nl tlutlrrtlc whtt, willh Ihcir aJvi.frrc, flrcirlr nn tht tul.icr tt Ir.r ahldy Rctillirnth /,f /hr /rllrrwthil+t ;arr crlrtlctt I+y thr tlr:tnt ill Ihr mrrlira) alh.u.lt Irq wrrff< ill lllr trln+lnt~r r.t r.tllt'r n/1 1+tnt lirlrr in tllr f.lhul.rl"vrrt t,l t.l•r rirn. r,l r .. rrlr•.It Crli,6 nr• w1r.. I/nvr t~.util il, rtr ~I m tl.r lury.r.rnl 11.1vr ,.r~r. n 1•,1• ~ ~.. 11„ n r.r Irt It .1,~1 ,..nrr ,d I11, r 1,.1\r 1•ct'n t.rrl,ll.llrrl rn r . /1bst t•acts of Rcpc>r1 s Fach recipient ill a•T<thacco Intluctry Research ('nnmtiltce Rrant ic tccPnncihle htt thc inilial prcscntation or pnhlicalirrn nf thc retuttt r11 his tetcarch in cv:icntilic meehnRs or in afpmpriate scicntific jt+urnalc. FolhtwinR are ahctrat•tt, appnwal by Ihc aulh,rrs, of rrtcara'h.rcl+t+rlt wilh acknnwtctll•emcnt af cnpptttt (rcnn the 'f ( R C. that have arpe:uctl in ccicnlific jttnrnalt tince the f,isl Rcporl and IhruuRh July 1959. Ahttracls t)f earlier rif+crt by Frantect which appearcd in previrnrt reLnrls of the Scientific hircclta arc lictcd af Ihc entl (if Ihis tection. -Ihc namc uf Ihc ccicnlict Irr whutn the I I R.C'. grant wRs tnaJe is Rivcn in p;ttrnthetis where tcynited. lhctr rthshnclt have hccn grou(,cd under five henllinpt /('ancer Retcarch: 11, Ilnroan I.unr, StuJiet: 111. Ilc:vl antl (:ircul:tlitar; IV. "Itl hac'cn (•Itt•utiatry: and V (thet Sludict. 1. l'nn.-Pr It errnrclr "T"ISSUF SI'I'('If K'ITY 01: SF.R(IM ('OMPONF ' NlS." fly S 1) Yrrl, M I) , W I: Scll•, It S, C. IltrRt,l. A tt ,:,nA F. W. IIAPNra Ilk , M 1)., wilh the aid of R. Rtlttrtutrr>tn, M f)., 1)cismlrncnls ill Mctticinc antl Phytiu- 1ttRical ('hcmictry, 'I hc Inhnt Ilnpkinc ( Inivcrsily SchtN+l .tt Medicine. II:Jtirnore, Md .•/ A(. .1. Arfhll'r,t n/ Jnlrnnd Afrdfrirv, Volume I(11, par.cs 411.V4R, /unc IVtV• (T 1 R.('. gr.mlee: I4atncc) !'urf+o.r n j.rrnf.: Scrum prrtlcins incorporate amintt aciAs very raf+idly, anJ it tcernt jnatiti:thle 141 cnncluJe Ihmt Ihie prrKCas likec place within cells. linder a Ityf+rllhecit derived frnnt a Iheory uf cell retlwmce Itl tlanctRe evttlvcd in thic lahoratttry, thc teramt Rlohulirts havc a ccllul:tr t+tipin Itt+nl a l:rr fe variety r.r LWrhart all of Ihe litcucs of the h.K1y; they cai:t(+e :unl circul:NC in Ihe 1wtJy Iluidc, and Ihen reenter Ihcir recrcclive cclh ttf nricin In rrtume Ihe (olc in prtacin nrelalHtlictn in which they were involved before leaving lhe cell. 1:><fx•riulenls were devited Io Iesl Ihe thenty that the ct++n- Tv.nents nf notmal hnm:ro cerum I+tnecss tisene afxxcificity. 1•r.rrrdnr..! 'I iatncc frttm hmnan nrF:mt (kidncy, muaclr, tkin, thyroid) were obtained frcchly in the r.peratinR rrKtm whcn prtstihle; and hunt:tn heatt, hrain, liver. cpleen. lyml+h nr.de, at+rla tmd cr+nnective licate were nl.tained Lt+t1 rm+rtcn. Fta injcctir+n intn rahhitt, thc matcrial w:ts utrd firsl ac a cutf,rncirtn in c:ttine anJ I:rlrr in the It+rm of a eenlrilulteJ aul+cr- nalan/ nf Ihr cutfrcnairtn Imrnnniralir+n of Ifhe r,thhils (trnccrtfcrl until an adrqnate level rlf :rntihttdica wat ehuwn ('tnac rraclivily wae temrtveA It,r aetlain tanpea nf tlihttL+n t+f anlircn arnl anli.ctttrn 1 he I+rrt'if+illn Icat w.te nscr) ttt rttintatr 11Lr Lr+.crhlr lintila t.f nnknf/wn arrum fq ft/ ;tnti/v-n fhlu /ifnt ami nlaft (ft .I/rlnf•cinl.tlc Ihr ttrtlrr rrl rnnpnilutlc t+f Ihc antiprn .In1lhnJy I+ret ipiLtlr Al+lrr/rlai.tlr t nnrrt4 Iealt :thn wcrr ettnlfnt IrA (lr..finlr•r Itlt• Irtulta tll..w Ih.d Iltc auti\cta Itrclt.+rct1 rrt,m :tnr+lhr•r tltc circ, willt rt•I:rtivr tf.ct tlit lly frn tvanf+t+ncntc ill a ainp/c Mnn:m tlrp.ln, will Ir:tclinnalc ft:lrrt tl1 Ihc .rrunl ftrtrtcinc nl inllivirlual Ilrrtnnt hy ftrt/~lnt t/r.n {I

nf rret-ihilinc lhc tctrtlt[ art rcl+rr,tlucil.Ic: alart c.rch ftt•tcc.n at t•arir,nc lirncc fhat i tlillc'rcnl I+itlcrn nf t+rccil+ilin fr:rt'lirtnc, Int•:tcurt•rl I,y lruri( n1 scrnm thlu(7nn 'Ihrcr fnttt imlicntt Ht,rl acrunt ptntcinc atc cttt:tinly nnt hrrmnRcncuuc f+ul can t+e tlivitlcd inlrr many indcpcnJcnt fl:tc/ir+nt I+y anti- lictnc tcra, antl he11, In cnnfinn ffte cnnccf+t divclr,f+crl ftr+n+ wr,rk /+n litanc d:ttnne thul (,rnlcrnc rlctivctl fn+tn ntctny ticcucc tircnlalc at [crunt prr, trint lhe rccnllt ilctr fur+virle furlhcr cvirlcnce 111a1 titcnc tpccificity tlr.ct titt in Ihc tuarurnal U/hrr I:rnnfrrrr: Ametifen Cancer ScKiely (Natitmal antl Nlaryland I)ivicirtn), Americ:rn Ileart A[st+eiatinn, N:t(inn:,! Imlilulcc nf Ileilth, Oamnn Runyt+n Memr+rial l-uncl• Millnn M. Frank I-nundalinn, an<1 1he Nnt)ema ('nrrt,nlir.n "-IIIM(/R-11OSf RI{I.A'CIONS htIRIN(i f)F.VII(/fMFNf ANO A1-- 1FR ftT (7RFSSIUN tW 11(I? TttMt)R " 11y 1 rnctrltt R C'Fnrt+t>,+. 1'.ttWARtI 1t/1ftNlr K nnll f'I,wAtttt 1 S< Illrn/ Ki, f)cl+,lrl/nent of IfirKhrnt itlry, I'ntdh:tnr I/nivercity, New Yr,rk ('ity (1)r ltrecnitk it now 11 (he Wclltnmc Rcac:rtth I ahrnatnticc. Iu/k:thnc. N Y 1.4rrlucrt of llin,lrern irrn, nn.! hinlrht.ir r, Vrrlumc R1, fi,pct 4•1 S\, )uty 1'1S~>, ('1 I R(' Rtan tre ('etccttl,+) 1'urprr.r n( .Nnlr: f'revirwe ctutticc in /hic I:thrrratr+ry hive chnwn that ciRmficanl than~ct txcur in Iltt wcil•19 antt alan in (ttc nnclcic aciJ ct+ntcrn Iralinnc (if [I,ccdic tictncc tlurinF Ihc 1.•rr,wth of Iunrrut in ihe ral, anrl tha( fltt(+resence n( aul•l'1r1:1ntn1/t h1lnl+tt c11tt('c MCeta[et in (f1e llcncytll+/tnttctetc nci/l ( 1)NA I et,ncenlrahr,n nf Ihr Iivrr :tnrl Itmp, where:tt rtrncenualir,n 1+1 rihnnucieie acirl 1 ftNA 1 nray r+r tnay nr,t chanFe, tfcltcntlinr nn I/te t t(+t uf Itumar. ln view uf tht n:tture ind ncwrihulirrn of (.r+/attium antl ite inl- pnrtance in cellulir nrrl•rhulient, it. 1rvclt wcre ft+untl tt+ 1+e rcl:+tetl In nllter rhennmena characlcriatic t+l ner+ldatlic rrr,wth It wac decitle'l Irt t.:uninr Ihece facttrrt in ct+nnrcturn wilh Ihe prrrwllr :uu1 rcl•rcacinn of v.1lion[ n'n rlacia in rntt nnd mice I'rnrrdnrr.: '1ht Murf+hy Sturm Iymphrnarcnrn.j wic Irancptan(ctf in Ihe f+ecloral rcFir+n of m tle 11r+tVman tate hy tntant of a trtrc-m antl tttc )cntcn sarennri in flluc Slrntce f arm[ tatt Suy.cncit,nc c,f ('14r)R rnvcl,tiJ lenkcrnia ct•II[ were inrrcolaled in the ri)'tlt fcrhaal rcRir,n nt malc ('57111 / ft1(11)2 mice f.iver[. hrnR[, kidneyc and [Idcenc were u.lirpated after the anintalt were cacrificrrl, antl tf+t'cilnent of hrrne m:trrnw and h1tMNl a1.n were Iakcn ('hemical antl rhycinh+yical th:+nt-cc duting dcvelr,l,ntcnt and afler rePrettit+n t+/ thc Intntnt werc [Ihulicd 1'-inrf7nK.: (itrrwtlh of 11rc 1vrnplnrc;ncr,ma in Ihe tat wat accntnrmnitd 1+y an incrt•act in 1)NA ctrnlcnt of livcr, lanp antl cl,lrcn anJ a dccrrict t+l I)NA in htmc ntnrrnw; rd lhe litcucc mcnlirmed. t1,lecn alnnt• th/.wcrl a clrar.`c (incrra[t•1 in c,axcnir:ttirrn r+l 1(N1; Ihc I+,+la[tinm cr+ncrn(ralir+n uf livcr ntlarr rr+cc (',+ncrrn(ralitm nt I)NA in Ifrc lunf rrru dnrinp Iht• rlrvrl O, rn f. r. nf,rnrnl t,t thr Icn.rn a:vtt,nrl, whilc I(Nn tctnainctl nnth:tnrl•d; fhrnnt Plnhin, ef,etilic prac•ity, anrl Irdil tnlirk rd Ilrr blraHl were rlcl,treactf tn:ukcrlly. aml a1l:mtrtl rnininrum Icvt'{c wlrrtt lumr+t circ tccr(hrd 2(Ir: ++t Ihc l.rK1y writ•hl If,r Icrrktmi;r h.rrl n„ cllrtl r,n 1hr 1)NA n/ livrr n, Iulnr, rn Il,r n,.,.,•. 1-, u..1n,i,1 t rnr ur tmr/• tTNn .,n.l a.Irlrrnv m „1 Ilir .r tr•..nr r t When thr•tluce afnre-ntcnli.nncd u+mnrt tegreaced, cach of the chanRes lcctril+cd w:t[ rcvcr[ctl and n/.rrna) pal(crns were re cslalrlishcJ ONArr Rrnnlrrr: Nalirmal ('anccr Inslitnle. "A('(ION OF ('1(iARlil'17: TAR ANI) SMOKfi ON ('111:.M1('ALI.Y INI)Il(•f~l) ('Alt('INO(;1?Nf~SIS." fly I(t1WAR1t 1~ IIt/1tMAN and A. ("I AwK (ir+rt / tN, 1)c~:vlmcnl of C'hemislry, Stanfcrrll l/nivcrcily, ('ali(nrnia. Prr[rnl alJdrec.rc: tiunt t.ahcxalory, f:. 1. du Pnnt de Nemunrt & ('o , Ncw;trk, 1lctaware, anJ I)cparlment of Ilinclrcmictry, (lnivercity (d Te><at MO. Antlcrctm 1(narilal and '1-umar Inditule Tetat Rrprrrrt .rn IlirdrrRv and Afrdit rrrr, Vul 16, pages 333-145. Fall 195R. (T I R.C. Rtanlce' Ciriffin) Pnrlrnrr nJ ,hrdy: Ac certain weak earcinttaent or nnn-carcinnpent have acted hath at tyncrgittic and as anlaRnnittie arcnlt in animal e.(.cti- mcn(c, it wac cnncidcrccl tkcirahle In dclern+ine whelher ciparclte crn/,ke or ctmdcn[alc wr.uld enhance (or inhihil tbe ernrrse of a wcll cttahlicfx•rl c:nt'inr,genic tcrlurncc, namely Iha/ rc[ttl(inR fram feedinF Itt rale a Aier tt+ntaininh liver c.rrcinrrgt•ns. • l'r.r.rrhrrr: In thc /ira/ e+lxtinttnlt Iwn Frt+upa n/ SpraKnc 1).twlrr lualt ratt wcrc ft•d rliclt cnnlaining I/AF (2 atclylamintrflnnrcru ) (t+t Itt•nlxlc of (wtt and Ihtce m/.nlht. Onc Rn+up wat c>tlarted ttr the srunkt• /d claml.ird fillerlets cipatrrte[ cannked in a rnachine at the tnte uf 20 eiRatettec an htrur, R hnnrc daity, fnr 12 tn 14 wccks. In tuthcequtnt Icslt (he ratt rrccived amnlee al tF/e rate of S ciR:rrcltct nn htrur. R hnun daily• 1 he uther Rnrur n( ra(e wac injectetf nn allernnte t1ayt with (11 nrl of n ennclencale rre- rarrcl by hurninr ciparclTC Inhat•co in arlaa (unncl: Ihe cnntlcnca(c waa sutftcndcd in Itt•hnut oil at a cnnccnlr:rlinn ut S11 mR./ntl. ('nntrlds rtcciveJ Lear,ul nil nnly. 1n 1he secnntl exf+t•rimenls eiaaretle smnke eondensale, commercially preparetl in a smokinR mrchine cltxely duplicaling httman smnkinR, was in- jcctctl in matc :rlhinrr ralt nn dicts cnntaininR tither I)AF or 1'.Mc11AF1 ( 1'-tnclhyl-4-dimtthyliminnltentenel. Other tals on Ihe samc rliclt werc rain(t•tl Iwice weekly wilh the tamc cnrtt/cnsale on shavecl arcat on Ihe hat'k of Ihe ncck. FinrlinK..: lnhalalinn (if ciRarelle [rnoke antl injeclilrn of thc lahura/r,ry ciF;nellt cnnricn[-.1te tfclay the al.f+t•arance of the prccanccrrnr[ [Ia1e in raft fetl 1)AF, nt ctrn in frrrcc tlam:tpe to the liver and in delay n/ tihn/lyvin h+werinR nf prcc:rnccr•+uc liver Nn protective actinn tu( laf.crralnry ctmr(cn t:tlc w:rt tdncrvctl in r:t1t fcd 1'-McUAFI, however. Atlutiniuralitrn ld thc cr,mrnercially prrl.:tred cil!arelle [mnke enndene;tle trt ralt Inl eilhtr car cinnp,cn dirl nul alfrc/ thc ralc of cnnccr indnclinn of Ilre (inal Inm/+r irtci drnce 11 nrutl t+c r(.ctq•nirrti Ihat Jiflcrcnl clmtkt lar frat'lirrnt v:rry cnn tirlr•taldy in c•rnyurtutir.n rlcl+endinR 11114111 n Ihe cnndilittnt of cl+tn(at[linn and n(fher (.rr/.qt, "t(YAI l/ftt)NA I I IN-1('( IVI' S1'RUAI)IN(i ('Al'1(tR OF f•IIIRINI: t:N1)11M1•((tl/11 CI('1(f•111)NN 11111Itt)N11" fly F. IlrrKrnl,lRr:rP . M S(.R/K[KIAH, ;IrIrI P (' IIARrt t, Ilin Rtatatch (mlilulc, Inc ,('arn hrirlrr, M.rat, an,1 1>r+[tt.e II )alktnn Mt•mrni:rl I thrrr:rlruy, F1nr Il.rrhnr, (tfr f'r..r rrrlrrerr .•( Ihr S,r, rr fr f.•r ( t1•rrirrtr•n6d nt.,f..pt• rnt,f Mi dn tnr Vnl t)'), r.r/•r. t.+,S r,hR. 1)rtrmhr r 1'/tK ( 1 1 R(' rr:trtlcc' 1h,ml,tirl.cr 1 11

Prnfrn..• nf -trr.lr: Ihe erpcrinrrnrt wcre tlctil•nrd hr rnracnrc the clTrcf rd ulert+nc in tl.rciding Intlin ink in file rlcrmic uf Icct animilt antl to cluci- d.ttc itt n+rthini.m lhic rt•cc:uth it intt•ndct/ lt+cl:ttify r+hccrvafitmc rnatlr during tfuJn•c td hi+Jr+gic activifirt rd t'n+h+ntctrial cccrctit+nc (ntrr++nr) t+htiint-tl f+y ccrvit'aI lipatinn in mit'c, which rcvrilcd thal crntle uft•rtme t•nhancec inlrndt•rm J clrre:rd nf lndia ink. I'...r.•.fhrrr: Inrh:r ink w;rc injt•ctrJ inlt:nlcrrnally in Rn+upc t+f rnature malt and frmalc RI M antl IIAI It 'c micc Sit grt+uf+c cnmfxitinR ?7 1(I M malrt rccciveJ India ink nrarker cnntaininR 611, I?lt, SIIU aml IINI(1 of hyilurtmitlace, (1Vytl:rcc), and fhe cprcat) w:rt cr+rnhatctl wirh thal rccult. inP fnrnr cerum t+r RinRer't solutinn. Five RUM milrc rcceivcd India ink ,nd frcch ulcrnnc trt+nt micc rtf the aame tl.t•cicc, :+ntl rhe ytrc:td w;tc c++mparcd wifh thtt in mice receiving Intlia ink anrl tcrum. FfTcctc t+f utcr- r+ne frnm IIAI ItIc rnite wcre rneaanctl in 19 m:rlr intl IS fcmalt rnice t+f that tpecirs given India ink n+arkcr aml utt•rt+ne in five difTerrnt cr+nccntra- litmc, antl the cprt•ad was conrpared with India ink and scrurn injrctiont FiRht IIA1 11/c rnalct were given India ink antl hyalurtmidate diccr+lvrd in utcn+nc frtnn mice r+f file tame cla-cicc I urlhcr It•crt were rn:ttlc in dc:+tl fiAI Il/c mice ckin (•t+ntnrl e>rcrimcnlt wcrc c++n.lutlcll in t:thhilc. file standard accry aninral I++r the cprc:,Jinf I,tfnr. F inrlinR.: I lie rrcullt indicutc th ct+mrnt•rcial 1Vyrlocc en!h:mrcc Ihe sf+rcat!ing td Intlii ink in thr dcrmit ~+1 f mice rnnch at it th.cs irt file rnhhit. Intratlcrn+al injct li.+n t+f rnnrint• ufcrrmt• frtnn IIAI 11; c rntl Rl fv/ mict• enhancet tKrcntlinR nf India ink in live mice of thete trecirt IIAI rl ic utcrnne rv+Irntialcc file ryat•atlinr t•fictl r+f Wytlicc in livc 11A1.11Jc mice. hnt is wilhtmf cflt•ct uf+++n injctlit.n inltr dr;trl IIA1 Il/c ckin ItAI It/c uler- nnc dt+cs nnl drltt'Ivrncrirc I+valurt+nic :+ri+l irr r•in.r '11rc pt+trn/iilitm nf Wydatc hy ntcrt+nc t++n4d hc cr!+Ltinctl hy incrc:tcc r+f inrr;t tlcnnal laccanrc ciucctl hy infl.in+nr:tfi++n nnrl t'ncuinF wiJcr tlrltuci+.n nf thc en7vmr. ht•nce a grealcr tfircatt 1 he nalure t,f file cnrnrt+ncnt r+f utrrt+nc rec!tnncihlr h+r prnvt+kinr. inl!:unnr:+li..n rcnlaint tu I+c +Ictt•rrninr+l :rnJ rn:ty wt•II hc a nrucr+~rnfcin. • RAlOA('AN111I1NtA I'Xf'I:R1l1f N1A11 Y INT)ll(•U1) WIIII A11:11IYt ('lll /! AN I11/11 NI: IN 1111 ('Itl(-Kf N" Ity R 11 Rv;retrN, M f), 1'rn(racr+r t+f 1':+rhnlVRv. I/nivcrcily t+f Icu:tc Mctli( al (lranrlt• C:tl. vcctnn ••1 MA .4rr lnrrt rrf f)nrndh+l. et, Vrtl 7'), Irar.ct 11').147, ( c!. rnary 1959 'lhit r:+!rcr ditcncuc the cimiLrrily nf a alnarut+nc cr1l tuntnr frt++luted in file tkin r+f (hitkrnc aflt•r h+c:tl afq+licilinn r+f rncthyhhnl:tnlhrcnc ttt thr kcr:ut+actnfhrmri in rtnn "1111: ItI Sl'IIfA IUftl• til•S11 M IN I111: N(112MAI. WIIIl'1: 1TKIN I111(.!( •' Ily It I1 lttr.ru+v, 1)rl+:nunrnf nf I'ctfhr+hq•.y, llnivt•raity r+f Ictac Rlydic:rl Ilrint h, G•tlvrclnn I'nrdrr r C. irvn r Vrd 1>t • I+al•ct I'1!+ 710. J tn uary I')tq. "•n1f'('IIANICM (1! 1tfM(rVAI O1• I t tffl) ANI) rAlt l lClft A I1 h/Al1 1(fAI 1 ROf\1 1111: ftI Sl'IftAltlltl• IItAr 1OI 1111 I)I/CK " Ilv It 11 Itu.rw+rj I At /.4r, /rnrt .f I'.rlln•L rv, V.•1 67. c I r1+ru:uv f'rn f..... ..~ .In.ll.. ,\n.+ln+++it .rl I+n.ln+l•. n+.lrtt +n Ihr •.Imly ++I inl+++r+l I 4 I ' carcint+grnecic in Ihe recpiralnry Iract af file white 1`ckin thrck m.ide if nececciry In cclal+Iich Ihc "nnrmal" for this hird While 1lhc analunric ttruc tarr l,f the req+u,lt+ry cycft•rn ic similar in many wayt Itr thal f+f rnammalc. Ihere arc cerlain rnntl:nncntal different:es Iha/ tupgctl afotrssihlc v:rrialir+n in funclit+n l.inlc :tflcntinn hat been given to file mcchanitm trf file rerncrvcd nf Onid anA p:trlicnlare nr:Nlcr frrrm the retpiratttry tract nf hirdt. Pr.rrr.lur.•c: In llre first tludy I:Hen was injected ttt protluce rnnltlingc (tf file rt•crir:rtnry tr:xrc td duckt. Tt, study hhaKl capillaries in the InnR, an atlult hirrl wak cacrificed and salinc injected immediately into Ihc pul mr+nary artery; wht•n Ihe saline returned fYnrn Ihe pulmttnaty vcint free t+f rcd cellt, India ink was injected into the pulmonary artery; after the ink h:rd ctnnrolcted a tr:rntit, secfinnc uf Iung were preparetl fnr histologic ttutly. In the tecttml ttntly itntnnit saline, flnnretcein stxlium, saccharatcJ iron t,xidc, India ink, liquid petrnlatum, .nd l.iptvdium spnres were given intralracheally tn sep:tr:rte grnup~ nf duckt, which were sacrificed after varying intcrvalc of eafyt'turet. lhe thoracic and abdominal vitcera and fhe air sacs were nhcerved under ulu,violct light for flunretcence in the IunRc, air tacs, liver, gallhlatlder and intetlines lhe Irachert and hrngs tuhce- ynently were renn+vcd intacl, and scctitms were taken Grr hislningic stndy FindinRs: lht•re are nn lymph notlcs in the duck, unlike rnantrnals 1here are lymrh channelt in Ihe lung which drain inln the larger lymphaf- ict, which in turn cnnunnnicalc with Ihe thnr:rcic tluct and then ernply intrt the vena cava When particulate matter is put into the Irachea, it rnually can he dcmimcharcd in the dilatcd parahrtrnchi at Ihe(+criphery tuf Ihe lung and in thc larger air tact. l he cilia on the ervilhelial cellt in the respiratttry tract degencrafe rapidly following deoth, sn care mutt he e><crcisrtl in e.prescing an t+rsinittn trn Ihc ciKnificant:c td Ihc ahtence of cilia frtrm the will of the Iraclhca. In file ccctmtl ctutly, taccharafed iron n.itk and flunrrtccin ttkliurn p:rccctl direclly thrrrurh fhe ervilhclial layer nf the recpirnttrry 1rac1 inlrr the ctruma and Ilutruph file wall t,f Ihe hltwwl ve%sclt aml/t+r lymphalics P:utirh•t nf India ink, Flt+hulct nf l+t•Iralatunt, antl I ilawliunr cf.oret nroi gr:rtt'd 1hn+uFh Iltc I:tyer of epithelinnt and cither cnlercd the hhw+d vetat•Ic antlinr lymhh:rticc ,hrectly t+r were pFhagtrcyti,etl within Ilre ttrnrna hy fihrn. hlaclt anJ hictrK yfrt. 'I he Irancfer nf Iluillt nml patricnlatc m,tler frnnt Ihe rccpiratt+ry Ir:u't Ir+ the v;ttcular syVem nccurreJ rrin,:trily in Ihe air cact "('AN(T.It O1: 11I1; I lIN(i - 1111[ SFX RAfIO A RFVII*W OF '1/1t: . 1'RO111.1AI " Ity I lrt rN Klar tntt r ind R 11 Rrr:rx)n., I)t•partmrnr nf P,Ihr+h+py, llnivt•rc+ly nf Ie.:tc Mcdic:d Iiranch, (ialvcttt.n 7rtnr ltrpn.tt rrn /1..rL.et urrJ Afrrlirmr, Vnl. 17, raFct 2'1 4R, Slain(! 1959 (•1-1 R(- pranlce: Itirth+n) '1 Irc nv:tiLtldr lilcr:thrrc r+n Ihc cex rnlin ttf cancer nf the lunr, ht•Iwcrn IR71 and 10S) t,ac hct•n rt•vicwcd 'Ilrc rnalc tn ft•rnalc rntitr in 1(IR atuttict 117.6119 t;rct•c t+f Iunr. c:urcrr 1 v:tricd frnnt (1 7. 1 Itr 21/ 1!. 1, with Iht• nvrr +( r r,+li.+ Ihvt• rnalr t.rct'c It+ t+tnc feur:dr t:rte I rnm fht• l+v:ul;rhlr tl.+ra it n1+IK•:u. Ih:t1 file int rrntr in lmrl.. c':un rr hat hrrn rrralr r in rhr m:+lr Ihan irt file frm:Jt• IIr+Wcvrr, flle IfUt•tlJt+n mav Ihr ;t%k r+l hr+tv n++r. 1t +•/ Iltit thtfrtrnt r It rt•nl antl huw rrrnt h ic nnly a(+ I+.trcnl'r Ihi, rt•vrrw .ht+wc file clalt• nf t:nnfncir+n rclcr:tl.lt• A+ file inci+lcntt• t ( 15 14

rd Inng can(cr in fbe milc an<I ft•rn;t(c. I)ita are avail:thlc tn chnw th:lt the malc frnlile "mnrlality rRtcs'- fnr tunr rancer w•cre i1 alwnrt the camc Irvcl in Ir)14; f,y Ivl() Ihey werc 1 7:1 anJ in IVNI hacl increiccd t<+ 4(, 1(('utlrr, 1. Am Stat. Acsn t(1:7(+7-2R2, In reviewing all the tlali, it <Inec nnr af(,e.r cnrrect fr+ accer/ Ihis r;,rin of 1 7: 1 a4 a ctirling pr,int It w(wld arrrar fr<,m this tevicw Ihat the malc-ftmale ratin of lung canccr w,c arprn.inrelrly t or 4 /n nne in 1`)<x) inrl 5 nr 6 tn nne in 1955. "1Yf•f:S Uf KI Rn1tN17A11ON IN llfl' I((/MAN CfN(71VA." fly ). P WitN+,IANN, M I) , and ) Mr n R, Ph 1) , 1)ivicinn nf (h:rl ParhnlnRy, l/nivrrcity of Iliinnis, ('u/1eRe of Dentistry, ( hicay,o Inurnnf of lnvrsfiRa- ti.•r t)rrrr4lft,LrRv, Vnl 32, p,ges R7-94, f"chru:rry 1959. (T I R('. Rran- tcc: 1)r.lsaac S(hour) )'rrr/+nr• o/ rtudy r in sludying thc cpithclial cntfacc in the human RrnRrva, four tyl,cs of staininR rcaclinn werc fnund. 711rce cnrrespnnd fo tbc prrvinucly rccnRnhed dicfinctit,nc of hrll kcratinitalion, par:+krtatnaic, and nqn-kcratiniratinn, which atc ct,nsidcrtd as nnrmal varianls nf rhe RinPiva. 1hc fnurlh hsc nnl been dcscrilrcd hithrrto, and thc tcrm "incom- flcre pinktr:,lncis" ic cnFRcaled h,r it In tadt•r In clarify thc cr,ndiliunc in which thesc tyl.ca of ktr.nini?atinn t*ccur, i1 ii necec.ary lo suhdividc the gingiva inln analnrnically diarinct tcFinns 1'rn-,furrr 11ir,(.cy af,ecimcnefrr,m (hc cusrid reRion t,f gingiva or 32 rnen 27-711 ycan of age were sturlird microscnpirally. ('rlycorcn cnncenlra- (inn, tsrimatcd ae the dirlcrcnce in PAS fx.citivc mntcrial without and with diaHaac trcatmcnl, an<I the t/rprce of inff:rmmsliun in Ihe undcrlyinR cun- neclive tiseue, wt•re clacciticrl ae O, alifltl, antl r<,ncenlrated nr scvere. 'llte ennlycic includcd crcu and nr:11 cnrfaec nt the frce I-ingiva and Ihe alr:rcheJ PinRiva -__ the P<,rlinn in ri:rrl atl:tchcrl fn thc t,n,lh antl in f,arl tt. Ihe hnccal c,r linl;ual cur(acec <t( thc alvct+tar hr,ne FbnfinRrr lhe type nf keritinirntinn wac aaterf:,ined in a trrtal nf 214 rcginnc nf the RinRiva 1he relatinne hclwecn <lcgrce t+f kerstinit:,tir,n and Ilre ~,resrnce nf Flyct+Ren and inRamrrrslir,n diflt•r <lunnlitativclv, but nnl yuatrtativcly, in the crecl, nral, rond atlached areas 'Ihe dictincti<,n r,f "in- cnmf+Icte parakcrala.ic" -- madc p<+caihle by very careful ct:lininP It•t'h- niquee -- Lcrmiltcrl ecrirafe dudy nf aht,ut a Ihirrl nf nce par:<krratulic JrrRinns f'arakcralncic clill rcmaincd the sinFtc mncl ftnyncnt type nf kerntinitatinn. riccnrrinF in a litttc nvcr h-l1f nf the camrlr. Othrr Rrnnr.rr: Natit,n.il Incritutcc n( Ilcalllt 11. llrrnrnn l,rrrtr ,Srrtrlir•. "I tING VOI.I+MI' IN SMOKI'ItS ANh NON SMOKf 1tS " Ily IIr NRy IIt A( KnIrRN, M I) ,)rKll: ItRt171 R, I'h 1) , nn,l Itt NRV 1. l'AVt r+n, Ih I) I alw.tal<,ty t,f I'hvair,lnpit•at 1lvpicnc, llnivrraity nf Minnca„I:r, Minnc arnlit ,4nnrr/t r./ Inttrrnnl Afrdirrnr• Vr,lumc 5I, papca GR 11• luly I')tr) ( 1 I R(' f•r.,n(rr (Ir<,tc4 I I'nrpn.. ../ .tn.f.: lrrhattr, ann,linf- h,rc Irrnp t,rrn .rrtl,rrlyd :,a nn rlirdr,r.ir (:r<n,r in rral,ir:,lnry awnl,tr,ma nn<( l.rraxl,r,l,,,lnn.n:rry <litraar• l..rl•cly r.n Ihr haaia r,( t linir:r1 iml,rrai.,n It w.n r ra,vrlrrrrl 111m mr:rcurrnrrnt nf .,n.,l.rnrit (unp r r.rnt,.nlmrrn/t in rddr-r im/rvr,ln.,l. mirlrl fht 1 91 r exfxcled lo prnvide cr•mc infnrmati<,n concerning ulrimale lifclimt effects of smnking on brnnchnpulmonary function. I'rnrrfirrr: 1):rta were cnllecled for 221 business nnd firufessit,nal men of Ihe -I win C ilicc aged 47 lo 57 who participated in a lQ-year longitudinal study nf cardlnvascul.•rr aging. All were actively empl<tyed and were fsee of manifesl heart diccase, hyperlcnsinn, and grnss parenchymal lung in- vnlvement. All fi(Ied uut a questionnaite on smoking ha(.its ctvntparahle In Ihat of Ilamn+nnd --llorn of the Americin Cancer Society. Vital ca- pacity rf each cuhjecl was determined at reat, antl residual air vulume was delerrnincd a(ter forced expiration with the suhject submergcd in water in a s1inR sen1; 1wo tror more preliminary tesls were miJe to "train" the suhjer•1 so that minimsl vahtcs of recidual lung volume might he obtained Aftcr Ihe final immersinn, the subject was raised and breathed 0, for seven min- utes. Residual volume and nitrugen cacretion were Ihen measured APe and body si?e were elirninated as variahles in the lung rnfnme comparisons F7ndinR.: Vital cnpacily was smaller in each caterry of srnnkers. The diRercnce from non amnkcrs rt:xhcd a statidically significant level fnt all smnking categr,rics cnmhined. ResiduallunR volume was larger in alt cate Rnricc of amnkcrc, htd not conciUtntly at slatistically ciRnificanl lcvels 1'nlallung raltacity was not siRnificantly diflerent hetwecn Rrtmrs -Ilsc tatit, of residual volunu to total lung capacity was significantly plealer in smokera. ln a group which had saceesafully stnpred all cmr,kinR. Ihe lung cnmpartment values were similar to those of a group who had never smnkcd, and the r:+tin of residnal volume to tntal long esr:+cily was siFni- ficanlly smaller than in the current cmnker.. Stringent scrrcninR of lhc samplc for alhn<srrnal reapiratt.ry m:tnilestalittns, such ae hiatories of clinical asthma, puhunnary Iutxrrnhrais, chrunie prtNtuetivr cough, anti ehesl de• farmily, etcIudcd 11 suh)'ectc (22 smnkers and 11 "Never" n( "Stnpf,ed" smnkers): this left a rrcitlnal r+f (RR men in whom the same onler af di(fer. encec in IunR vnlume prevailed between cmukers nnd nnn-smukere as in the lotal samplc. The diflerences recorded were in the direetinn to he expected it amt.k inR is a facNCr in prtalucinR a furxlional increase nl airway resialance Jlhlhrr Rrnnt..r: Nati<tna( Flentl Inctihde "IIIf? [:1 11'l'IC O1,~ SMOKIN(: (IN '111F. RPSPIRATORY SYSII M IN NURMAI. INI)1VIfyl/AlS." Ry KFt.r.v T. M( KFr, 1)cparlrnenr of Medicirte, Mc<Irca1 ('nllcge of Snnth Cartdina, C'harlectt,n ,Cnurhrrn Rfrdi rnt lnurn<d. Vrrl 51, paf-es 111(1.11 (5, Seplemher 195R. 1'urpr..c rr/ .rurh: Itcc:+usc rtf the aancwhal cnnnicting cr,nclucinnc tlr:lwn frnm a numla•r nf aludics mea•urinR varinns napcclc nf I,ulmr,n:,ty functi<+n, it accn,c<( w<,rlhwhi(c tn sludy -1 rrrnr(, nf nurnr:rl inJiviJu:rls, cmr,kers nnrl nr,n crnrrkcra, tn dctctminc whrtltcr any cir'nr(ic:,nt tltl(clrnlr in t•aaily nrcaaurt•d vrnhl.llnty cnnq,nncnrs nf hrc:rllrinf cnuld hr nhtcrvrd itn 11re lwrt ~rnuf,c I'r.r.r.hn.: h1r•.,.urrmrnla t,f the vital c:yonr ity nnd m,r.irmrm 1.reathinf c:r(,aily wrrr t.,nir<I ,ud in 171, yr,unf, mrn :+(trrl 7(1 In 41 (RS^. wrrr 21 7R), in<turlnrr t.lt nun amr,krrc. 7) r.( tlre an,r,krtc .na 1cd Irt,wrut t,nr aml tw<r t,.r<k. rd ril•.:ucllrc d.uly tnn<) thc rrrnaininp 44 nnr h:r11 Ir, 17 1 r, ~ C.

tn r') t,nr /t.rck tleily 1huilir,n trf cil•art•Ilr nt:rpc in thc ctrru6inp pr(mr v:rrit•d /rnm trnc In I S yc:rrc In St/ td Ihc tnrr,kcrc tlrt• mc;rtnrcnrcnrt wt•rc ntaJc ht•/nrc an<I irrrnrerlialely aftet tmnkinp nnc tipereftc, :rttcr :r 1+crintl nf alrttincncc trf fnur t,r mr,rc ht,urc F-indinR.: Sliphl f,nt rrrrh:rhly m,f ciprtilic:rnr dccrt•:rtc in A,I.rt vitil ca- p acity in hcivy tmnktrt at ct,nrp.rctl tu nnn-Nlur,kcrc w:rc m,lrtl A tirnilar very cliFhf rlrcrcace in rnatirrrrl hrenthinp t:rl,.rcitv in hr:r.v vnr,kcrc ac cr,mpare(I fn nnn ernt,kere was nt,led Nr+ Ircnrl ttrw:rrd :r tlccrr:rte in rrn,timal LrrathinR caliacily with int-rcacinp yr'•rrc trf ( rp:trCllc nc;rl,c wl c nF+tt•rvc•tl 11 wt,ulrl ahrear• (+n fhe hasit t,1 tlrc.c dnJict, tlh:u n„ cvidt•ncc has Lecn lantluct•tl ttr thtrw 1h:d vcntilmt,ry lunt Iirm ic ti)•nifir;rntly itn raired in y(,unp, cmnkere ~t cuntrared wilh nr,n crnrAert, rnu ic Ihcre any defini/e evidrnece Ihal venfil:rtnry funClit,n in Ihcce emr,kcrc tlillt•re ar frcciat.ly aftcr smukinR ;( eiparetfe iflt•r crvcr:rl hnurc fir :nc~ftinence 1mm .mnk ing "SIIII)Ir:S ON Ilrl: ' NATIIRI? (W IIYf OXIA WI"r/l ANf) WI711(ltt1' ('1'ANOCIS IN ('/IR(1N1(• 1'Itl M(/NAItY I)ICI ACI''• Ilt Ilnnttv 1. !tlntr r v. M 1) , 1'rr,fcctt,r td Mcdrt inc :mtl 1)rrct Irn t,f Ihr (;rrrfnrrtl,ir;rb,ry I ihryefr,ry, Ihri.(rtily r,f Cnu/hrrrn (:rIrlnrni:r %tlu,rd f,f 1\ltrlrcinc. I nc Anprlcc (:..rrrrrrr r, Vt,l 1 1, 617 f,11• (/tlnF.cr I')SR 1'u./rn.r ../ urrdv: IIrit dudy wat nrarlr trr ,1(•tctminr Ihc n.rlntr r,f the arlrriis hlraul tlrrn/,t•c in Ir:r/icnlc, wilrnrnl t•nrl,hyccrn:r, cr,nrl,taininp nf Jycl,nca nnrl I:rlipuc trn rtrrtir,n :rnrl with„ut cy:mr,tic Ilrc :rrtcri:tl h1,rt,J rcflcctt tht• F,Ir,tql pnt c.ch:rnrc in Ihc lun/- " t Caruf,ht fir r.lnr,tl frt,m the frmr,r;rl vcin have hcen nutf:rlrn fnr :nlcri:rl fcm(,ral hlr,t,tl, whitlr tnay he tlirk in Ihc I'rccrn(c fir hl farcia 1'rurrrfrrrr: I r„rrtcrn mcn :vnl cic wr,mcn ;r/•crl 1 7 Ir, R I ru:rrle fir Ihe stntly pr(,rrf,; Nrcrc wcrr 14 cacc. r,f /il,rr,trc fir unknr,tvn t'tinlnFy. twtr caces of c:rr(t,iJntlt, Ilrrcc trl :rthctlr,vt :rnrl r,nt• t,l Irrl,uc crylhrm:r/r,cut In nnc fihnrcic t':rcr Il,r•rc w:rc actr.t ia1cJ :rl•.nnncrl•L,I,uhn :rnr•mia :rml in nnr,thcr hnmt'IrircI:rcic r'trinrr.n.rry fnnttirrn n,c;l.nrcnr(r,IC nnrl(•r varvinf, * Iccl crrn tlitit,nc c(,ncitt(rl fir Irrnr. vrdurnt•, ;rrtrri:rl Idnrr,t, ;rrrrl fminn,n:rrv vt•nlilalinn lhe Infal Irrrrr, t af.:rt'ily w:tc tlct rc:racrl in :rll catcc, :rn,l cnrrhyct•nn wns nut a factor. FYndinR.: llrrcc ctu(lict intlit'a/r that 1lrc ilvcr,I:rr c:rl,illiry nr(•rnl.ranc hlr,ck it nr,f a tipnilicanl ficfnr in Iht• hyfa,ti:r td rwlnrnna(y fil,rr,tic, cm- f,hycc•ma. In,l in nrrrcf fir Ihc rcl:tlcrl (r,ndilir,nc, tnch :)c tht• (r,Il:rfrn prnnp r,f tliccatct. Ihc trne cincc rrf tl.it (rmrlili(,n ic f,rirn:rrily r,nt• r,f rnc%truc/it,n irt which thc :rir ),rr:111rfrl /lr,ec rnr,t /•(t rlnwn Ir, tIr(• 1Ivcnl;,r Icvcl wht•re Ihe hlta,rl p.rt rtt h:rnl.t• t,ct rnrt l hit Jr:r/•nr,tit Ir:rt I,t•(n nnittcrl in Ihc pacf antl inc(,rrt•ttly tlrtcril.ctl F,r(crucc Ilrc /•r:rilc,l h•vrl% r.f hil-h ntv/•rn I,rc;rtfhint' ( 12 In 4(/" r,typcn) wcrc m,t ntr•,f. ctlq•t i:rllv wifh cct'rl mc flrt•nllrinl• 11111^.• rrcyprn m rcct crrnt/i/rrlct :,n in.trlt•rlu.,fc Irtl I,y whn h 1„ rnl(• nul chunfinp it Irhr :rlvrrd:rr Irvcl \. lllhr. Rrnnrnr r N;rfir,nnl In~lrrrrl,•• nf Ilr.,lt/r "II11 NAII/ItAI IIICItrItY t/l ('AIt('INr)IttA fll ftt! ItIN(i" Ily ( ir rrRr,r I INr1 rr.rrr( C\1 I) Mt.lrn C I 41 I/ .rnJ ('ncer r~( Cnl ewrrrtr It1 I1 , Ilrf,.ulnrrnlt rd fl1<'Ju inr.If nrl,~J,.t•y ,rnJ Cr•r/•rry. I l,r I Inrvcr.ilv •,t It,•• I.r J,r C, h„nf ,.I N1•.1h• rnr :ur,l 1 1, nlr•.Iry. If•v hr tf,r. Nrw lk I I Ytakf lrrnrnnl rf 7lunaric .ArrArry, Vol. 37. pages 2V1-.11)4, March 1959. (T I R C. Pr.rnlt•e' ShcrwotNl) I I'nrp.rv .r/ •rody: 'I tre principal objective hac heen trr pain new infnr- r f i m: tnn :rhrwl c:rrly cFhanpec in the Inngs precedrnR the drapntnrt n car- cinnma of Ihe lung anJ, where ptnsibte. In obcerve the alteratior» in tt-ray thaduwt, prc(eamp Ihe apl.e:rrance of clinical synrplums, with Ihe patsage (r( timc. 1'rrrrrrlurr. Over 41K) catet nr pnlmt.nary cancer seen in the llniversify fir Rtrcheclcr Ilr,cpil:rl were reviewetl• covering )bt) proved casee, tht: ma- jurity having bern diapnrrted within the pad 15 years. Rccort)s were ah- str:rcteJ and inh,rmathr,n was solicited (rum stnvivinR palienls, familiec, phyciciint, hncpit:dt, and other inclitutions where radit,praphe may have hecn Iaken. Any pact raditrgrapht availahle were fitheretl aml reviewed in c'tmjunctit+n wifh later filrns ntatle af tite time nf tliapnnsis trf c:)rcin„ma. ('ertnin ancill-my ttalictic:rl Jata were inclutled far general interesl, withtnrt for Ilrcr el:rhurali„n. F'irnrllnR.: Itarlirqtraphically, ohctruclive pncurnt.nitis was pretent in 17^1• trf fhe (:ICCt. Ir:ucnthymal rnacs in 21';•, hilnr mwlul,rily ill 2t)"S , hilar rnasc in atclcclacic in metliactinal ntwlcc ur ntatc in r)^.•, pIcural cllucion in R"',, parcnchyrnal fihrrttn inlillrate in t^;•, and nricct•Ila- netrnc MhntrrrncAitics in 4';:•. •Ihc ave•r:rp•e inlerval between firtl cyaq,tnnr anJ clinical Ji;t/ nt+eic wat eevcn mtrnfln. 'I he inlerval Ixtwccn the firtl radit.praphic cvirlence rrt cancer anJ its tliaFnrnic was frrur rnrrnlht ftlr all caces; Ihic lipure in(ludce a large numht•r where ntt x-rayc were laken rnrrr tu tlrc limc rrt ccl:rhlidrinF the tliaRmrcis. In the mtae eignifit'ant ptt,ul+, where raditrgrarhs h:rd been matrc cir< mtmlhs (u mcxc frit+r In clinic:rl t1i:IFntnic, thic dcl:ry was 16 mnnths. 'I'he ia,Lttett p:Irenchymal ntnlule muct he tkalt with ns malipnant until proved t+llrerwict•, cince eatirp:ttirrn nr the snrollesl ptracihlk rnalipnant'y Rivice fhc hcct pr„Fntrtic llle authnrt nlar repard the frcrciclcnl infiltrative dencity wilh cqnal sucricinn nnd slress the importance of slttdyinF such radirrFrirhit• c'hanfcc witlh carcfld attention tto cornparistrn uf Ixccc•nt find inr c with :rll nvairahle previnus raainRraphs. A mtrre cele(tive appmach is rectnumended in macc screening InJi vidnal p:rrt•ntt, Larli(nl:rrly fht'ce nver 40. shuultl I+e cduc:rlt•d Irr have ratlit,pral,hc rn:rtlr tmcc fir twice a ycar• by the sante inctallalirrn, tn facilitatc c„nt(.aricrtnt t,r Lrt•tt-nl antl pacl radiuprnphc. II ic nrpcrl th:rl alt n,t•ntpcnt, rtr.unc hc kcl,t av:til,hlt rtrr faturc ct,mparicnn, cintc cuhtlc chanl•.cc are I,ccl cccn Ihy (rnnl,:rrativc ttudiec 1I1. llrvrrf ltnrl (:irr•ulrUinn '•('Altl)IA(' 1l 1 I('1C (/1 IC(11'/tOII RI`N(/1.. NOKI ('IN1 1'lllttNF ANI) I 1'INI 1'1/1tIN1 INl'1/A11'I I 11 A\' 111 Alt) Ill fIt K IHtItINt3 1!(I ItIMI NIAI At•1I11)tIC ANI/ IIYI'l ItKAI I MIA " Ilv Cnr(rfe(.n ~' (ar/r,rAr4, 1,11 I1 A rrruNnr (' I)r 1/ ItN, IM , It1 I1 - In~1/1 1V 1V( cr, 1'h 1) ,•rml ~c~rr•r r Itr r/1 1, ~11) ,('hrl.nlrll,hi.r (irntr,rl II„tl•rl:rl :unl 1 Inrvrrtrty r,l I'rnn•.vtven,.r tir lnHrt fir I\1rth, inc ( nr r.LNr.m Rr v rnr h. V,•I tnut• 7. I,:,1•t t r,r,r, t,! `. lulv 1'tt'/ I I I It (• ctantrt• I1, Ilcl I 1')

I ll ~. I 1'urp...r nj rturiy: A mm+)xr ur synlralhlrn,irnctic nminrt have hcen cflrcfivc in rcttt,rinR cardiac aclivily doring Stl,kcs-Adims atlacks and catdrac arrest (fom other cansct, hu, thcy tail 1+r rcstore cardiac healinR or tu incrcae the slowed venlticlc rate in slanc uf thcsc stalrs Since mular xwlium lactate rraduced favt+rahle respt+nsc whcn Ihesc Aminrs were incf- fcclive, stutlics werc tmdertiken in an attcmpl to elucidate snn,e nf the underlying mcchanitmt in the alteration nf cardiac rhythm and tcslasnse to syrnpafhumimcti< amines at vati/+us plt lcvclt Proor.dur.: ('<,n,plcle hearl hhKk was prlyduccd in mongrel dogs and respiratory acid,rsis was induced by inhalatit+n n( 2(1 percent (-t)r in nayRen (or pcri<Kls of R to 12 minutes Metabolic aciJt,sit wat produced by intra- venous infusion of ommonium chloride ftrr a period t,f 316 to 4 hout.. Ifypcrpntasscmia wat prnttucrd by infusinn +,f ,sutl+nic pAassium chloride over a f+Cri<K1 of 10 minutes to one hour. Serial arlcrial hl+w,d san,ples were ohtaincct al a~hn,priile pcritkh in eacf, +,f thc ecfrcrimt•nlal ct,nditions: Acitlosis and hypcrkalemia, for dclenmininR chanRrs in p}I, ('O„ Ur, K, Na Antl ('I. In another serirs of ecf,crimcnts the circumrks hranch nf thc left cornn,ry arlcry wis cnthcirrirrd in t+rdrr tu :uln,inislcr drupt rlirrclly Io a Il,cali?rtt fa,rlilm t,f thr heart in flusrt largc cnnuRh to clicit h.cal trsl.ansc wilht,u/ I,r+ulucinR sysrcmic clTcctt Ffndi'nR.: Am,nnniurn chlnrldr acidnsit retulrrd in drerrates in pll and fr,lal hk-x1 (Y)t content astrxiatcd with a significant tisc in potassi++m and a fall in arnrm sodium kvclt, cnncrnnitant with a dnwinR uf the carJiac vcnlriclr ralc Anll t•lct'hl,canli/,Fraf,hic chanFcs similar to the find- inRt in hy/.rrf+nt~~tcmia f',rri.il r/ rrcttil,n /,f thc acidr,sis t,y inlravrnl+ut in(usion of nu,l-Nr sr,olrtrnl l:n t.,tr rc.nl,rrl rn .1 rrturn h, n/.rmal :,nl) in anne inNant-rt lu rn inrrrisc in alr..crltrr„rl,rr r.rlr t,lnrfic~nrly prc-llrr Ih;ln the cnntrl,l rAtr. 11cfotc an11 altrr aculn it, ,hr rr.l...n.r nl c:rr h.nimnl In v;,rinus in Iravcnnut tlntcs 1,t Ihc Ihffcrrnl trnll../lhr,rnin,ctu annrlt•s wat dctrtminctl, and a nearly lincir c,arcLali„n u;ls f,+um1 f+ctwcrn t11c +tccrrasr in rraf,t,nsc fu the aminrs ar,d thc +1rprcc nl ;,ciJ„cit In illditinn, there wns a dimin- ishcd risc in 1,14,40 (,ressurc Ihc intracurunary injcctinns hcftxc ncillusis rctultetl in inrrcasrt in irlil,vcntticular r:ltr cumr-In)tle to Itlotr f/,1111winR intravcnous injcclions uf thesr druRs. f)urinR acillnsis, thc pnsitivc chr+,nt,- trnpic cffect from intracomnary injcclirrnt uf +hctc :+mincs diminisht•t1 ac- cording In the ttccrrasc in rll; injeclinns nf trnall amr,untt nf mnlar trxlium tactate or sr+dinm hicarlwrnale at /his timc I+nalucrd a lransicnt chanRc in pll only within the vicinity of Ihc itlit.vcntticular picrm:,kt•r, hul injcctir,ns t,f thr AlkalirinR ARcnlt were inclTectivc in incrcisinp, the cardiac vrntriclc rate in the ehsencr +d at•ith,sit •Ihcse stutlirt lhctc(t+rc taF/•cs) tho the rrfraclnrincst In Ihc syrnra- thnmimctic aminrs is tluc lo Ihc h,wrrrll I,it and that currrc li+ln nf Ihr I:,Ut•r rrsll,rts their cflrctivrnctt. J Oth.r Rrnnrl.r: nmrricnn ltcarl /tstlKi:,tintl "•1I1N(•i1t)Nn( ('AI'II I ARY 1111)o; IN '1111' IIFAIIN(:, K(l nlt R1 C11 11 nNU K( l nrtl(l IM lt t't /t11tSl lt 1\tYtst Altltllthl trl " 11l(: I1</(; " flr S 1t %1 Itr rrn,r rra, I'll 1) , ir G . nml ht K+ras, r/, A1 1/ , , . F •11/ / t1+ ,c. I)rpartmcnt of Analnmy. University of Illinois Colkge of Mcdicine. Chi- caRn; and R. 1 IStNC, M D., Washin6lon University School of Medicine, SI. L.ouis, Mo. Cirru(nrion Rettnrch, Vol. 6, pages 600-611, September 1959. "F.hI:I:Ci- Of' IN7 ERRI)h17ON OF CORONARY CIRCUl.AT1ON ON METnI1Ol.ISM OI. TI(E ARRPSTED lIEART." Ily O. MrcttAt., A. 11rVRrN, C. S. IIIK:ANCAMP, and R. J1. f)INo, Washington University School of Medicine. Amtrirnn lrnnnol of rhysielfngy. Vol. 195, pages 417-423. November 1959. (T.1.R.C. grantte: BinE•) Pu.pn.e nJ .t,.r+r..: The Grst report deals with a morpholoRic study of Ihe (tmclional capillary vascular bed of hearts obtained under the follow- ing Ihree conditiuns: (1 ) the htart still bealing, (2) the heart arrested for varyinRp~ ritxts of lime, and (3) the heart arrested for varying periods ot tinte and then rrperfused The second investigation concerns the influence of myocardial ischemiA on certain functions of tnetlty production of heart m.,tcle. rrorrdurr.: In both sludies, the arrested heart was perfuted In ,rltu withrnrt inlerruplinR cnronarp circulation. immediately after intrtxluction of polassium cfdoridr tn provokc cardiac arresl. Special calhclers were intro ttuced pcrmiltinr the tolkcHnn nt sirnultancous hltwnl samplea /rrn,, the inflow tuhing anti the coronary simn. 7 he samplet were analyred for osy- Ren. Rlucose, ryruvate, laclale, and ketone,tMxliet ufam pcrfusinn, while rrtfusion was /merrupIed for varying peritxls, and alto when rr•tumed In part two of the first study e>tcised organs were e>tamincd hislofoRi• cally. The hhKnl contained in all hltrnd vesscls at Ihe time of perfusinn was trapped by simultaneous clamping of all vasculat channels. Ilear+s reper- futcd afler ri9 to 5 hours' circulatory arrest were atso esamined by Ihis technique. Erythrocyte sludics permitted contrasting analyses of arteriolar, capillary and vemlle relationship upon perfusinn aftct circulatury artcst, and in hearls which had remained in situ for the same lengths of lime withmrt tepertusinn. In part two of the ucnnd sludy. the chest of the animal was npencd, and circulation slnp(+cd by severinR the arxla. A sample of hearl muscle was removed immediately from (he left vcntrick tube used in manomelric 41 1~ es(x rimenls. The chest wound was covered for periods ranging from 4 htnrrs and another sample of heart musck IAken. Thus, each animal served as its own control. Slices from the heart musclet were takcn, al thickncsses within the limits for su11'icienl diliusion of oayRcn, and trans- terrcd into Warhurg vcssels, gasad with 95% (1, and 5% CO, for 10 minules; rendinRs of rrxlaMrlic activity wett started and continued at 10- minule intervals /nr RO minutes. FlndlnR.: In normal hearts, erythrocyte counls n( open ca~/illarks showrd a unifnrm dittrihulinn in 1he right myocwrdinm, and A Rradlrnl de crensinr. frum Ihe rpicnrdium toward the end++cardium in the left ntyn cardinm 1'ulaasiunt 41+hnlde arretted hrartt shnwcd a revcrac irradirnt in Ihr Irfl mr+r•nr+hum 1hr rrj'thnx:ylrt were I+tirntrd in t•apillAtics witll Ilrrir flnl tlJr. (Yin~ rninsl /1rc nralctl my+r'.P1rltial cell in nlmmal hralts, but frw nt nt,nr I,ar1 this rnlc++tadnn in Afretlcd Ilcal/s I"rvlhr/K ylrs In thr nrrrslcd hcarrs wrrr twr,tlrn, rnundrd, ur packed in c/nn,l+t' •11, n/wto I. w~ r..l...... •...11 n.l.n..w. 1\rr.•. m.nl ..t blr.tl.lwt. w.,nr t...r ,.r M.Jl.lwr, 11.,..•11. M,.,. I 41

I '11he arrcclrtl hcar/c ethrhilcd a weakcninR t,f the connective ticcuc elrnrentc r,f the Inytrt•ardiurn. lhe wcakcninR incrcated ac thc tlur:rtit,n t,f rnyr,cirdiil arrccl incrcaced In the src'r.nd ctody, etl.rrimcnlc nn the whnle heart recnltrd in a RraJual decline in mytrcantial n;yRcn ucage after Iwu hrrorc nfter four hrrurs, rrrtyFen uciRe wat ncRliRihk. Severe alleratit•na in carhrrhydrate mrtal.r,licm were r+h.ervr•J, such ofs a tiRnificanl increace in myr.cardial Inctate prnrlvctir,n. (n e.fa•timcnts with licanc cliccc• myncardial ntvgcn usaRe dec•Iinerl rnr,re rapidly and aerobic Rlycrrlycia lrhrk place in Ihe hearl muscle. ntRrr Rrnnt..rr, Puhlic /kahh Scrvice, 1hc 1 ife-Incurancr Medical \Rescarch Fund. American licart Asstxiation, and ifurrtwRhc. Wcllcnlne and Cn., Inc. "Tllt? F i 1TF.("T UW ('OM/'I.F.Tli IS('1I1?MIA ON TII[: INTRA('Iil.l.ll. I,AR Iil.f('IRI('AI. A('1IVIIY O1; "1111i W/If)l.li MAMMAI_IAN IIfiART'." Fly Mrt ir,r+ KAPtr+rcr rt, M 1) ,('h,rlct F. I1rK:AN( A10r, M 1) , and Rrflteter. 1. HIN(:, M.1) , I)cr:ulrnent of Medicine, WachinFNtn Ilni- vcrtity, nnd rhe Wathingtrrn Ilnivcrcily Medicil Service. Vctetanc Arlmin ictratirm Ilnarital, St. I.ouit, Mo CbtrJnrinn /trtrmrh, Vol 6, haRrc 115• 721/, Nrrvcmher I9tR. "TRANSMI.MItRnNE I:I.IVTRI('AI. IY)1I'N11A1.S IN Vf'NIRt('AI. TA('lIY(•ARI)In nNl) 1 1111ZII.I.A I I<)N." Ity ('nARI ts 1: . IIrr;ANr'AP1/r, M 1)., Mlt rrrN KARnrst rt, M 1) , Wlt t tuo,t I I f)ANr(/R //t, M 1) , an1l Ru /tAalr I. IIINr:, 1\1 I) Anrrrirnrr llrnrt Jrnnnul. Vnl. 57, paPes 214-222, Fchrttary 1954 ( T I R(' Rranlcc- Itinr) I'rtrp...r nf .rrulGr.r Recent cturlicc in Ihit lnhr,rilory hnve chrtwn Ih:rt the conrraclilc prr,tcine pre),:rred frr,nr humin hcartc retain their collrac- tility ac lale ac 12 hrrurt after dcalh r*! Ihe paticnl, ind Ih.it Ihe t,xidative en?yrnec in hcarl mueclr rerniin fully active for ccvctal hrnrrc aftrr inter- nvirm rrf cr,rvmnrv crrculalinn Ihc fucl ctudy ic cr,nccrncd with /hc ctlcclc t,f complete icchervii nn Ihe ef.,,nlinenus venlrictrl:rr action and rrclinF pt+trnlials rd the itnlated whole dr,F'c antl rahhil'c hcarl lLc accnnd durty aprliet Ihe micrtrf.unclure teclmiyne (+l I unR ACcranl (1. ('ell h('r+mp. /'hytird. J4 :1R 1, 194') ) Irr Ihc ttudy rd intlividual myrtcnnlial fihcrc antl attempls tn rclate electrical inJ mcchanical activity in alternation nf the heart in Ruinea piRt Prnrrrlrrrr: Seventeen rnhhitc antl frrur sm:rll dr+pc were ant•clFhetited :rnd whrde hc:+rrc wcre qnickl~' rcmnvcrl 11nm Ihe animalt and tUilq.t•d nf their re•ricardium f'crfucir.ns ht•Fun Iccs than 9(1 secr,nds after internrfHinn af tfre circulvirrn retnlted in immerli:rle frrrceful muccular crmtriclir,nt. •ihe (+rrfusir,nt were mainlaincd tl a cr.nst:ml lacctrne, with the hcatlc kept in a hathing etrlutitrn. Sfw,ntanerrut h•ft vcntticular mernfhr:rnr nclirm and reatinR ptrtcntiali were rrF.taint•rl hy rnicrr.r4cclrr,dcc arul rrcr+rrk•rl I rrlhrwing a hc•rirKl r,f alahiliralirrn, f.t•tfutir,n wac corldenly ur,l.l'rrl anrl the halhinr, a•hrlirrn rrl,lnccrl hy nnr,/lhrr rrnth rrtl ntyyrn frer 1•y I,rn,r t1turntinrt rnA c'vnlinunut huhhlinr willr niUr,t•crn, rhu. I,rrHlrrciny .rnr•ci.r In Ilrr tr-r rrnrl clurly hrirlc wrre tlnit klv rrm,.vcrl /rran Drlctrl,f I,/r,l rrrinri I,ir. 1-r6-l in 1 v,l,rlr,•n tr•n.l.mllv r•n~•.r,l 1.y e rui.Inrr n/ 'It• .,,,, r„ -,I s r r 1 I r.n „.. n. l•r Ir-n t•,•rr'nrr.rt• tt, tn rJ r; were recorded by micrtxlrclrntlea. Iikclrical I+otentialq were recorded frt,m mullipk sul+erfrcial vcnlricular cells in each preparatitm. A cnrldcn drop in I+trtential evidenced entry into a fiber. After preliminary trhservalitrnc and recordinRc td cnntractions in the spontaneously bcalins or electrically driven vcntricles, arrhythmias were produced by applying acnmtrne to the heart aurface. FindinR.r In the finl cludy, slxmtaneous membrane action potentials (+ersislcd for 20 minutes following the cessation of coronary perfulion lhc earlictl change in the action putential was a shnrteninR of itc duratitrn, followed by a prnRrescive fall in the amplitude of the spike. The resting potential shnwcd a diminutiun to 65% nf the control value. Sudden ex- hrsure of the whole heart to anoxia markedly shortened the duration of the action 1+otenli:J four minutes after interruption of the coronary circu• lation. The findinRs suRRest that it is the active stxlium pump mechanism that is injured by annxin. 11 ic pnccihle that the chanRes observed in the mem. hrane reclinR ptNenrial are due to the inhihitit.n of otidative phtxpht+ryla- tirrn by annRia, which is very similar to the eRecls of inelahalic inhibitors rrn electrical Ikdcnli:dt in Ihe Ixnrl, In the secr•nd cludy, simullaneous recording of eleclrical activity frtrm two fihcrs on the vcmricular surface of Ihe guinea piR heart revealed partial cynchrnniem of action Rr+tentialt when the fibers were in chrce ptoeimily, hul not when the e>aplnred fihtrs were at a distance. Single fiber electrical altcrrnnc was frequently uhaerved tlurinR venaricular Iachycardia ancl was accr,cialed with mechanical allernans. It would appear that alternation n( the hearl. both electrical and mechanical, may he related to alternate varia- ir,nc ii hehcwinr nf individual fiber rnernhrane and contractile elemcntc. ~()tfrr. Rrnnrnr,r American Ilcarl Atcncialinn, Ihrhlic Ilcallh Service. VJ lhe I.ife Incurance Medical Receareh Fund, Rarroughc, Wellcttme h('tr . Inc., and the Veterans Adminisrratinn. "l llt: IIt: ' AR"r IN ANOXIA ANI) ISC'IIfM1A." I)y Wn I uost 11. 1)AN• Irrtttu t1MI RIt IIARr. 1. ISrNr;, Ikpartrnenl of Medicine, Waehinrlrm Ilni versity, St I.rnris; Mrr. Rririch Inurnal n/ Anrtthr.tio. Vol. 111, Irar~es 4Sh• 4R5, Ocltncer I9tR "f111: . SIIRVIVAI. Of- I--.X('ITAIIII.ITY, 1?Nt:RGY PROh1t('TI(1N ANI) FNFR(:Y III'11 17.A•11ON IN 1111' ' IIIiART." fly 111rt trrN KAa 111 cr It, M I) .('ItAel r s t: 11rr;ANr Amr, M/) , and Ru ttAt+l, I HtN(:, M 1). ('irt rddrinrr, Vtd. I K, pagec 915-945. November. 195R. "MY(K'ARI)IAI M1: .'IA11()1 ISM." fly R 1 It1Nr,, 1 1) ('nrrnlrmrltv, (; Mtt nAl, and K KAICtr Annnlt of Inrrrnaf At'rclirinr, Vul. 49, raRec 12111 121 S, Nr,veml rr I95R. "Ml'(K'nRl)IAI 1 1 I l('11:N('Y " tly R 1 IStNrt and (7. Mlr ttAt - Aanul, .•f rhr Nrrr Ynrh Arrrrlrnrv rq .Crirn(n. Vr+l 72. Article 12, r:rpct 5tt tSR, I rhnrcuy /', 1')Srr ( I 1 it (' grantee IIinR) All h,ur atuAirc I,rrct•nl rt•viewc n/ work hy Ihe oulhntc nnrl nlhrrc 1'rincil,al cr'ntiuciunt rn Ihr frrct ntr Ilhut Ihc cornldclcly nnrtclc hc:trt wrll cr,nlinrrt• tn frrrxtir,n ;rc n I,nnqr rrnly art hrnr. nc the res/inr mrnrl.r:rnr Iw, Irn/i:d rrrrrnin. .ullr, rrnrly )ri/•Ir n.n) ar tinn fwHrnli.-tlt nrr Prnr-tatrrl an,l hrr,l,:rt•.r/cJ Ihe atrurn 1N,IC11Ilalt rlrtlrne anrl dicalqxar r,ver at,rurl 211 41

i minulrt nf c1m11,lttr /tcl/Cnlr;r At tll/t flrllC, nl-IIIICr 111C mct:lhr,lic prrKCStCt nor lite cl+nlrnclilt rrnlcinc :Irc irrcvrrcrhly Il:crnarcll 1 hc cetvmd review Jiscucacc the Ili/lt•rcntc in turvival limt of the three mvj1,r hinlr+pical hmctinnm nt Ihe annwic heirl rnncclc. ('arlhic excita- hili/y it nlntt vlrtnerahle, while energy Trnrlncli+,n and pirticul;lrly enerp•y utiliralir,n survive Irlnper As Ille al,ilily rd :1ny c,rp•an Il/ functinn tlt•Ivtndc urnn the rctitr,ncc nf lite we:lkcsl link, Ihc 1,1tc nf ea•ir,t.rlity nf canliac n+ua-Ic whith is induceJ ra/.idly Ihy icchtmi:l IcaJt to Jc:r111 l1f Ihc whnlt nrRanicm l he third diccuscinn it a revitw of carlliac rnetahnlittn nf /he heatinR and the arreslcJ heart, a matter of increatinp impl+rlance to the heart sur- Rtnn and the intcrnict. It alan Jeals with Jicnnh:lnces nl carcliac mctatwllism in congestive heart failure anJ in mytKardi:J icchcmia and annxia. In cnn- Rtslive heart failure in man, mrlahr+lic chanpts are ahsent anJ myocardial otyRen consnmplinn is n/amal In cfxintantous heart failure, myrrcarJial o><yRttl cnnsumrtinn and efliciency are diminishtJ, but the nsyRen ertlrac- tinn ratio remains unchanged In exlxrirncnl:ll rnyncardiat infarcti/m in ani- mali and in hcrnlnrhagic shlxk, on Iht other hanJ. lite heart rnuscle rtleates lactalt and Lyruvale inln Iht cr/rnnaty vein t,l/wwl Tht tamc nhservatinn wnc made a/lcr intcnuplinn nf lite lnrnnary tirculalinn /lrr varyinR mricxlt of time. •To tlale, cnrnnary artery ta/hctcriyatinn has failcd in the Jctrclil+n nf mclalallic alttratinns in heart mutclt cellc which wnu1J cithcr preccde cell dtalh nr take(+lace in cellr in whith mttah/+lic chanpes are revertihlc. I~ulure sluditt Lrllhahly will he JircctcJ Inw;trJ a cnmhirntirm nf mctalhnlic Ihal- anct slu/lirt utilitinR coronary cinnc c:llhcteririlinn and rn7ym:uic sludics on heart rnucclc alices. I hit c.in t.cal he accnmplichcll by lite uce of rnJi/.- isotnres lhe fourth review finJs Ihal Ihe decline in cardiac efliciency in a ntrml.er of chnil-al cnn,hrinnc, p;lrricularly cr+nRetlive hcarl failure, retults from lowered ntyl+carJial energy prllJuclinn rather than energy utili7atinn "('IIANGF"S IN IRANSMIIRAI-(TNIRAC VF.NOl1S I'RISSIIR/i IN MAN 1)IIR1N(7 IIYPIiRVF-NIII A1ION" fly 1nnN W Fr ucltlN and WII t tAM K. IlAk/lt TfIN, Iletnr+tlynarnic I.ahnralnry, ('ardinv:rtcular Re- st•arch I.nhltralnrics, Ikpirlment of Internal Medicine, anll 1)ivisinn nf Anesthesinlnpy, Ucparlmen/ uf Snrpery, Stite I/nivtrtity nf Inw:r ('nllche of Mtdi(•ine, Il+wa ('ily. Inurnul n/ (Yinirol Irrrr.lricnlirrn, Vul :17, (iafts I SJ7-I 541, Nnvcmhcr 19SR ( r I R(' Rrantcc f ckstein) Plarpn.e of .rnrlv: If the JcnamatralcJ tllill nf IarRe ammunts of hIrH+J (rnm Ihe Inrtarm vcins durinp hyl.crvcnlilitinn wac pl-ncrali7rd in lite heriphtry /d lite hnJy, Iht vl,h//nc I+I hInINI in lite central vcnr,nc rettrvnit might incrcast: hut the fall in la•ri/dltral venlws Tressure which al•.n lxxnnt during hylxrvcnlilatinn iml+licc thal ccnlrcJ vcnl,us hrccsurc :Ilc„ Jr(rraccs lhit s1uJy wat undcrtaken t/+ ,ttt•ts /he na/nrc Ind mapnilnde nf ch:lnpct in rntan r.rnrvrnnol ctntr:J vcnnus l.resacre du/iny. Ihy(,l•rvl•n1i1:1ril,r+ PrnrrrfrVpt SIInUltancnus mr:lcurrrrncnts rd t'cnlr:J vl•nnnt I,rtaurr; in Ira rdrural 1lrraalnC (raul~cd I.v (hanprs in tanl,hal•cal hrl•aslnr, whil Il Icnd h11,t f+.ratlrl), rr,nrlrrrn.nl crnlr.ll vrm,us Inctamt (t11t 11i/lrrcnlr brtwc/•n IhC firat Iw1+ n1r:ltnrr111Cr11t). r•ml Crld r.l,lr:lllqy I t1. 11nH1'r+lrelr~•p, were q.l made nn a pn,utv nf rncdical ttudtntt in res/in6 cnnclilinn anJ again after al least two minulet of roa><itnal intpiration and passive ewhiraunnc lhe hyptrvcntilalinn was practiced while breathing air, while hrealllinR S% ('U,, and while breathing 5% C'Os after inlravenutn adminrclratian of 5 mg of phcnlolamine methanesul(onate. Fin.lirlR.: Mean intrapleural Presture fell about the same nminrnl in each kind of hypcrvenlilalion. Mean ccntral venous Ptecsure fell rtRularly during air hyfx•rventilalinn, hul remained essenlially unchanRed Juring ('U., hyrervcntilalinn; it fell siRnifKantly, hnwcver, after phcntnlamine aJminis- tratinn. The pressure ditlendins the central veins (transmural pressure) in- creased JurinR hyrervenlilAtitM in almost all e><Ixrintentt hecanse intra- pleural pressure fell more than central venout Pretsure. l-ransmurat Prea- sure was siRnifrcanlly Rreater during Ca)r than during air hyptrvenlilalinn hecaute central vcnnut pressure did n/N fall appreeoahly. Tlte increase in transmural central ven/ws Pressure suppnrtc the sup,ges- 1il+n that Mnoll shifts centrally durins h~Perventilatian. The enhanced eflccl uhnn COr addition is consistenl willt 1he auRRestion that hllxid is pumped Ietc rapidly rrnrn Ihc central veins. lhis could he attributed to lite dnwer heart rale with ('O1 hyperventilation II could altn mean that diaslnlic ven- Iricular tone it incrtated with the higher concentration af ('Or in the in- spired Ras. Tlu respnnse to phenlolamine administration it aJJilinnal tvi- dtnce that CO, breathing is associated with an increa.e in the circulating level of cateclud amines. ~ •'('IGARf:TTI: SMOKING, SERUM ('llOLESTf?RO1., f11.(X)T) PRIiS- SIIRE, ANI) II(/1)Y FAT-NF.SS nI1SI;RVATIONS IN FINI-ANI)" 11y MA11tt1 KARVl1NFN, M f)., Ph.I)., and Fstt/t ORMA, M.I)., Instiwte (il Occupalional (icalth, Ileltinki, Finlaml: ANrFt. Krvt, M A , Ph I) ,)rrcr'F IIar17P1t, Ph l)., anJ FLAMtNtO FIOAN7.A, M.1)., 1-ahlttalnr7 r+f PhysiolnRical FlyRiene, llnivtrsity of Minnesuta, Minneapolis. (nr. htJanza it now al the Inctilute of Iluman Psychology. University of Nr,ples, Ilaly.) 7Ar fnn- crt, March 7, 1959. paRes 492-494. (T.I.R.('. grantee: Keys) Purpo.c• n/ arnrfy: flnth retrospective and I+rntpective slatislical stndiee show hipher'mnrlality rales from all eautea and (in anmt Iral.ett) frrlrn ischernie heart disease amonR amokers than amunR non smlrktrs In the ahsence of evidence that habitctal ciRarelle smukinR directly accclerattt atherngenecis ta incrtates suaeep/ihility tn thrnmhneis, arRunlenl as tn whether a caust-andtlfect relationthip eRitts helwten cmnkinp and heart Jiceasc it s/+eculative. l'herefnre, it wat pertinenl tn inquire whelhtr sm/+k- t•s lend t11 JilTcr ftmm non emnkers in characterislics nlhtr than emnkinR hahit, cuc'h at scrurn chnleslernl levelt, nrlerial hhwrJ pretture• anA relative nhetity. Prn.•r.frrr.•: An tl•ilkminln~icnl atudy wat hepun in 1')56 /+f nacn livinp. in rnral an•as /,f Vact anJ Wccl I irdand, later t.(`anlleJ tn inchlJe mrn of lite fitt dl•pat/l.vnl nnd I,usintss nnd rn+tcasinnal rncn in Ilrltinki In M,th rurnt nrl•as nrcn :yrJ ?(1 Sl) were sclcctcl) in a nurnlar of tmall cr+nnnuni lirs, twclultirnl. civil c/•/varnls. Itrn(Hxary residents, nnd thllsr knnwn 14, I+t ill Mnd r1f lite men w/•tt fann/•rt nr limhtr w/nktre, 1,u1 t'ar drivrrt, mrlh:lnics an11 alu,l,kr•cl+crs were alalr samt+lyd 1ht rnl•rt w/lrr Iltnnr/hl 1/+ t.t rc(+rtccnl.ltivr nf IFhcir arc ptnul,s in ,ht twr+ :Irt:n, hllt Ihic waa nnl 41,

t <7+ r] r) nrccatarlly trite of thc Ileltinki r.lmple. All the men were acked In rrfxnl for etarninalinn in the mr,rninR witht,ut hrcakfatt, hur no inctructit+nc were given ahtwt tmr,kinR. therc were 160 rcRulir ciRarelle cmr+kerc and I(.5 men who ncvcr amnkcd in Ihe curvcy. F7ndlnR.r At alI aRec and in all rcpirrnt (cxcel+t in the Sp 59 aFc praup In Wcat Finland) Ihe tmokcrt had ciFnifrc:mtly higher average ccrum chm Icslern/ valuet tlun the nnn vnnkera At all afcc anrt in all rrpinnc the tmokers tended In have slightly Inwer hllxxl rrestvrec Ihan the nnn- smokers; the Jiflrrence in tyckrlic hhxatl prctaure wac hiRhly tiFnificanl. that in diastolic Idrxxl prcasure significant hut Ircc irnprcctivc. In htllh rural rucat the srrlnkcrt rcndcd In he tlifhlly Ihinncr th;m the ntm smnkcra, hnl in Ilclsinki there wat nn clcar reL•nirln between tm„kinR arld laldy fatncta. The dila frr,m f-inl:md divlay inlercdinR dincrcncea between tmt/k- crt and non tmr+krrt hut they dll not evlain tllc uriyin nf the differtncec, and the cnnchrtiun Ihat hihilual cip:netle cmt,kinR c:lncrt srrum chnlrtlernl tn rice, hkxxl rrcewre to fa11, enA Wy tn hrtc rit ic not jnttified lhe kind of f.rra,n whtl trntlkes, in cnntracl Itl the nnc who ic nnt inclinrd In take u(~ amt,kinO, may Le einq,ly sn ctmctituted nthcrwiu thal he Irndt tn have elcvatrJ ttrurn ch,llcttcrrd, hlw hlrwwt preasrnc, and Irl Le rcMtivrly Ihin Orl..r Rrnnt„r.r Americin (lcart Atatlcialil,n, r-innith Ilrart Aca+cia litm, the Sciencc Iltrard of the ,1Clile t+( f:inlind, and Ihe Sipr1J Juccliut i Stifrlcc (Ilrltinkl). "1'1IR11117R Slltl)Ir;c IN ('rlUl /?S7FRO1. I f:.VFL.S IN 1111: JUIINS IIOI'KINS MFI)I('AI- SI111)I NIS 1111: . 1~11'I:('f O/: S1RIiSS AT EiXAMINA 1IONS " Fly ('sat,t tn+F 1110111 'Inrl01ut, M 1). and Fnkalrrn A. MuRrtty, M I) , f)erirtment r,f Mctlicinr, 1 lie Jr,hnc f hlpkint ltnivrr- Sily Schtxll td Mhlicine, Ilallinunc, K1t1 , InrrrnnJ trf ('hrnnir l)itrntrr, Vnl R, pages (,frl (+6R, 1)ccrnlfrr 1')tR I I I R('. p.rantre: Ihtnnac) Purprrrp o/ .tnrf.r At part t,/ a InnR Irrrn ctntly r,n (a,cciF.le frrcurttlrc of hyfx•rteneit.n and cnrnnity Jiacacr• c,+ntinw,uc ctutliet have been nlade nf the ehelleetertd Icvelt u/ succeecivr cliceet nf rnrJical etutlenta I he clasc of 1961, entering in the fall r,f 1457 wat the ftlurlcenlh elatt repietered in Ihr shtttr. 11 waa deeitled lo tlhtain chnleaterr~l dclrnninalit,nt nn Ihat claas durinF tlie ftnal anatomy eRamina/inn Itl cnnlfare with the Icvelt t,htainrd trx+n after admittirro, durinR a f+critxl of etrese in which a Mnnan cadaver wat being ditarcted by the tthnlcnta hrr the firsl lime• and (lurinR a nnrmal dnJy f.eritxl 1 he final anatt,my t•watninatitm it rn,hahly the Rre:r/ecl ttrrct en ctlnnteretl by the aturlcn(c at a prt,uh durinR thrir ftxn aeatlcrnic yrirc Prnrrdrrrr. I)txly weiFhl, hl+xal rdrctcrne and hcarl rate were nlraa,rrctl. then hlrxxl wat drawn ft,r chnlrctrr,d dctcrnlin:+lit,n and a circulafirlr, rntin n(+hil colmt' on adrnitaitm In rnctlit'aI c(ht,r,l ('I rct I -Oclnhcr 14t 7), dutinP final an:dtnny ret;lmin:llir+na ( I rcl 11 . Jan 6 I(1, I')SR ), an,l tlur inr. IiIxrratray ttudy la•rirxla (lyd 111) hctwcrn Jan 21 and Af+ril 74, I')SR, l)le ct;llituical analycia it haced nn the ~n,trx r+la nf Il.r S) mrn with cr+mplcle r'h++lectrml ttata /r+r all tlhrre tcctt Wr+n,t•n were rctlutlrJ bt•cautr of nnctnatrt+nt in chtdc•clcrtd Icvclt witll thc nlrnctrn:ll cyt'Ir F7nrllnR.1 Illr Illr:+n c111/Irtlrrl+l IrvcIc :lt lratt I an,l II were ci/•nifi+antty hirlhrt Il,in :,t Irvl Ill, a limhn). t,mciH, nt wirh Ilrr hyl+„Ihr•cic 1h:,t •rtnm tl,+dretrr+.l I, vrl, ri.r I,rrinr I+cri,xlc nf trcct Ihc rucrnnl+h,l tl:,t:, tul+la+rl Ihe view that the studentc were cxfrcriencinR more strrts at Test II than at '1 eat 111. '1 here were nn tipnificant diflcrences in hndy wcipht between the t rce lettt and no pronounced variationt in hahitc of e><ercice, dict, or S I nkinR. l.rr Rrnnror: Natit+nal llearl Instilute. "OIISI~.RVAIIONS ON SOME POSSIIIL.E: PRFCURSnRS OF FSSr-.N- TIAL IIYI'f?R I I:.NSION ANf) CORONARY AR11iRY UISFASF.. VI. COMPARISON OF IIIF CIRCIJLA'IURY RI:AC.TIVITY TO TIIE ('OI-f) PRF.SSUR T[ST ANI) 10 ltll: SMUKIN(i TEiSI'." Ily ('Arut- ur+r Drnrtl.'Inrrn+As, M I)., rA(-P, and rntulrNn A. MuRrt)y, M.I)., E)e- Partmenl of Mrdicine, lhe Johns Ilrtpkins University School of Medicine, Haltimore, Md. .lnnoh o/ Internal Midicine, Vrd. SO, pages 970-9R(/. April 1959. (1' 1 RC. Franlre: Thtnnat) Pnrpn.r nJ .rurfy: It it generally recnRniscd that hyE+ertentive patienta thnw greater lability nf hhx,d precsure under various fnrmc of strcts Ihan do nr.rmotentive Lertl,nc, and Ihat such lability it a characlerittic of the individual which rrrrrdr. the development of hyf+erlensitln. NormtNentive suhjeett with esraRl;eratcJ ree(~tmtct lo the cadd prestnr anti to the Lallictn- cardit+Rraphic tmt+kinR tetts Irave heen called "normal hyl+erreactnn; •.s there are markell individual dilterences in reaction to Ixlth tetlt, a clnter ; definition of nnrnlalily aRExart detirahle. Prorprlnr.: Cold preasnr teslt, with hhxxl pretture and nulce rate meas- ured after immersinR Ille hand in iee waler, find hallittr.cardinRraph teslt after smoking nne ciRaretle, were enmtucted on .1R6 heallhy medical tlu- dcnts, includinR l(1 wnmcn, about a year aparl. Of the mcn, 162 were smnkcrs, 155 m,n-cmt,kcrt, 19 former smnkers, and the hahitt of 20 were unknown. FJndinR.: In thr cold pressnr tett. Ihe average hlcxxl prceture ritet for rncn and wamrn were quite timilar. Thit was not true of the heart rate chanpc, where the men showed a mean risc of 5.4 hcatt I+er minnle while the women showed a much smaller chanRe, plut 1.2 fx'att per minute. There wat a tendency frlr the rnapnitude of resfxtnte In decreate with aoe. No tiRnificanl diflcrencea in reslx.nce were found amrrnR the different smok- inR calcKrKies. In the hallicltlcardinpraphic tmnkinR lett, the mean riaet nf syatrll•ic and di:ninlic preeture were tmaller than /hate fnund in the cold ptesa,r Itat. Averal;c I+Itxal pretture chanFet were not tipnificanlly diflcrent in wrlmcn and nlrn. I+nt the heart rate chanpe of Ihe fcmale suhjrclt was tiR- nificantly Freatcr Ihan that h+und amtmp the men Iltre alan there was a Iemlcncy fnr tlhc rccrr+ntet to dt'create with aRe. Nnn tmt+kert shtlwed a tipnifit':1n11y Frr•.llrr rice in cyehdic rretture than tntt+kert am) a vnallrr riu in hrart ralr Ih:rn cithrr arm,kers nr hxmrr crnt,kcrt. It is intercclirlP t1,:11 tlle tiFnific:utl er+rrrl.llirm hrtween syttnlic re atw,nae to trm,kinr and diactt,lic rt•tlx,nce lu cnld was farririrr in rnrn aml neRrrriri in wtrntrn I?ach td Ihc Ihrrr mt•.1turrmenta in Ihe Iwtl Icelt chnwcd ahlar+amatrlv n mirrn:ll tlictriF+nti„n, ar, th,t they all ~~fx•ar L. I+r tr,ntinurnrt variaf,Irt Any llivitlint• lint• +•r c„tt,nr la,inl tll dichnltui.h hyf+rrrracltat ic thcrrft,rr f.utcly :ul•itrarv It it tt,ntluJcJ Illal indcl+enJcnt inlt+rmati„n lc pamcd 47 d r+ m r.

I frorn each tesr. Accurdingly, Ix.th Irsrt n+ay contribute to the appraisal uf individual circulalnry reaclivity, and nnc tes/ dt,cs not replace the other. (Ithrr Rrnnt.,rr: National Ilenrl Inslitule and Velerant Administration. "VARIATII(JTY UI' ('IIOLES71iROL Lf:VEI-S IN INI)IVII)UAT. IUFINS 11OPKINS MF:I)I('A1. SIUI)ENIS, WI111 O1ISI;RVAIIONS VN STOPf`IN(: SMOKIN(:, VIIAMIN Br= AhMINISlRAI7(sN ANI) A('U I F INI E( I IUN." Ily ('APrrt tNF IIPIrFt t- 111(IMAt and I-R1FnA 1-AI- MAN [?rSPNaPR(i, Uepaflnlent of Medicine, -The )Vhnt Ilnpkins l:nlvcrsrty School o( Medicine. IrullNin o/ rhe Inhnr NopAins llotpifal, Volume I(15, pages 1 4-50, July 1959. Purpo.w of .tudv: Previous slutlics of ch<,Icsterol (evels in rncdical slu- denta showed that although the mean level Icnded to rise with age for file group, the factor of age alone did not account (ru the widc ddlcrences in cholesterol level, nor did age always parallel this level in a given suhject on repeated fesls All Ihe varied findings suRgest that there is much more to Ix learned about the binlrrgical variables allecting Ihe cholesterol level in a given individual, nnd ir wis dccided to study the cffecl of three such variables on the choleslerol level in n/ew indrvidnals in a particular envir- onment, ralher Ihnn file more utunl trrxt-secliunat sludy of a large Iti,ptl. lation Pr..redurt•r: Five male and nne, fcritalc slotlcnts whu vr,lunlrerrd to slop smoking during Ihe tesls and itve mile contr,ds fillcd out delailed yucs- linnnaires on srnt,king habits; an nl•pf.risal of f:rl content uf the tlirl also was mdc, and sernm chr,leslen,l Icvcls were dcternrined fxfrnr, during and following the tesls 1)urinR hcrithl I h,dh SS and (' Rrnupt snu+ked file cut. ttrmary amount: durinR Ircrir,tl 11 Ihc SS slutlcnrt give up tmuking and file C group continued to trnokc, as Ihcy did tluring pcriud III; in 1)u Ialler, Iwo SS audents resmnetl srnt,king nflcr 7 R wccks uf nul .rnt,kinR, t,ne after the tenth weck, nnd the olhcrs willydrew frr,m file enperimcnl afler 5-7 weeks. 1)uring peritkl IV vitamin 1117 wat atlminislcrcd Ir, the 5(' snhjectt and to one SS suf+jcct who h:rd resmnr,I smt,kinl.'. Scrum chnicsrrrr,l kvels were also studied in seven u/ Ihc tuhjccls who h:rrl icute resl,irnlury infec- tions. FindlnRre Tlre six "ttop anr,kinR" vnlunfcert, whn startcd with low cholesterol vahres (nn inleresling tlcRree nf sclf-sclectinn as et,mpared In their elrqmatet ), showed no dcfrnilc lendcncy to devehqt significantly lower eholeslerrrl valucs tlruing file etl+crimcnl; only tine shr+wcd a nr:uked gain in weight, beginning tr><m after ttnpping smr,kinR. 'I'wn of file tix suhjeclt showed a significant f:tll in mcan c1u,Icatcrt,I Ievclt rI11rIr1R vil:rmin Il,r adminidration; thcrc wcrc no t'r,n.iclcnl ch:rnpcs in lattly wci/fit, hlr,nt( pressore or ceart ratc during Ihis tt•%l ntnrc inlcclir+ns r,f file inllucn7al type wcre act'umranied f.y a sh:rrl. transitr,ry rall in chnlrsicrnl levels in three suhjects When suf.jrcls were grr,ul,c,l f,y Ihr pr:tnrl nrr:rn n/ .111 chnlratntd vnl urs per man, llre total viri,hitrty and thr l ird„)vt al v;rri:rhility r,f Ih„sr with higher valnct wrrr r,n file wh,dc I•rr:rlt•r Ih.tn rd Ih„sc wil/t Inwt•r vnl,rt•s At any given Rranrl mt•:rn thnlrstrrr'l It•vt•I. Iht•rt• at•rr imlivirlu;rl ,lillrrrncts in file Irmlcnt y a,w;rr,l t nnN.,n, v~,/ t hutr.lrr,d 1,•vrl, r,n thr rmr Ih:,n,l, nr I,m rn.,rn,n, nn Il,r n111rr I4 i nthrr Rrnnt..r: National Ileart Institule. "1'I•I T('I OF NI(-UI INf:ON CIIOI.IiSTfiROI.-INI)lt( I~I) A'IIIf~RO- S('(-IiRUSIS IN '1111? RA1211fT." Ily 1)IIANP (i. WPN7F1.. Ph I)., IAMFS A. Tuan,Frt, M U., and Or/NAttf Kttsn., M.S., I)eparlment of Pharma- cningy. Ilniversity of Kansas School of 1'harmacy, and Veterans Adminis- tralinn llospilal, Kansas City. Mo. ('irculatinn Rrsrarrh, Vol. 7, rapct 2tf,-261, March 1959. (T.I R C. grantee: Wervel) Pnrpn.r of .rttdyc It has been reported that nicotine increases the plasma chrdestcrol levelt of male rabbits on a chuletterol-(ortified dic/'. The purfxrse of this cfudy wat to determine the eRccl nf graded doses of nicotine plus a high cholesterol diet on atherosclerosis, using the following crileria: scrunt chnleslcn,l an(1 phosphnlipirl levels, electrocardiographic chanp•es hcfnre and after crgrmavine slress, and gross and micropatholoRy of lhe heart and conliguont vcssels. Prn.•..iur.: Six groups, of twelve albino New 7.ealantl silt-weck nIJ fcutale rabhitt e,ch, were fed varinut etperimenlal diets, antl dclernsina- lions of htnly weiohl, scrum chole.terul, and phnspht~fipitt and electrrK:rrdi- ograrhic activity (hulh with nnd without erRunovine) were made initially and every eirht weeks thereaPter for 24 weekt. All surviving animals were then killed In arldilinn lo ennmination for nitcroscopic palhr+ttrRy. file dr- gree of aorlic sclerosis was grossly graded on a 0 to 4 scnle (less than 2% trp In R(/ % (if the ttdal surface involved). FindinRs: lhe addition tu fhe choleslernl regimen of nicotine, equivalent in amount to human consumplinn of twu packs of ciRarettes daily, did not significantly atfect body weight. serum cholesterol or lipid phosphnrus, ur grots aorlic allleftKClrrtKrs under Ilre c.mdilions of this test. l he nicnline- choleslerol grnula dernnnslrated greater rnorl, lity as well as grealer elcctro- cardiographic anJ palhnloFie evitknce of cardiac involvement and peri- pheral vascul:tr changes than did tire ehnkslerol onl7 or nia,tine-only rahbils. It it suFgesled that prolonged constriction of the vettels involved or other undefint•d aclinns of nicntine created the proper physieal and/nr metatarlie envin,nrnenl fr,r the tkMrsition of cht+letterol 'Ilre nbscrvaliun that the vnalt ct,mnary vcsselt were Ihit'kencd and fibn+lic in Ihe nictrtine only group wnulrl slrenRthen this ptrssihility. IV. Trrlrnrr.. CItr'miar,y "METAROI.ISM O1.- MtillllnNINR ANt) Pli('T1N IiS'l l?RlF(('A TION IN A PI.AN f I ISSI I1: . " fly ('t FrFtran S SAir). RtrttAan 11. Iln'RrttrM. I't tr tt At nt "srlrlnr, nnd IAMFS IIrrNNF", Kerckhofl I.ahotalruirt rd Ili olt,Ry. (-sh(tunia lndihrle rd 'TechnnhrPy, Patatknn Lnrrn,rl r,f IfL,I„ALrrl ('hrmiurv, Vt,l 211, I,:tRcs 12R-1}I, luty 19tR. ('T.1 R(' ft:rnk•e 111,11 ncr) I'rnp.rv .rf srrnfv: Althr,nrh the tranarer of mrthyl frtrm mrlhinninr lu nitrt,rcn is knuwn I„ „t(ur in Ihe tynlhcsis rd hl:rnl alknL.irls, thc nrctham ism rd sut'h mcrlryl:rtir,n :rnd of mrthy) transfer in gt'neral is little un,h-r sHw,tl In Ihit sluJv. Iht• trans(cr nf file mcthyl 411 mrlhir,ninc 1„ I+cclint the Lrint ilrrl nr, thyl :u, rl,t,n r,t I,IaM lissurs, h:rs 1MC11 invratit':rtcrl. es wrll .rs I,r,%.il,It' inlt'rn,,,h.rlt. m file tr:rns/t•r In a,lditi„n, the t'r'nrvs ,d mrlhvl

grnnlrt frnm ft+rn,altlehyrle and the N+le t+r phr,tl,hnryl chl'linc in rne/hyl transfer hia hccn ctu/licrl. 1'rn-.luri: 1 he e><hcrimcnlc hnvn been c:lrricd nu/ with r+il ceedlinp, cnler,ptilcc eacictd front the l+Llnt and flr+atcd in Ihc dccircd qaantity of mclahrrlitc. It hac been thnwn in carlit•r sturlict 111:11 Ihc Iranclcr t+f mcthyl to faclin n+clhyl cstcr grt.ups is spccr/rd in thic ticcuc by the I,reccnct nf the plant hnrrnnnc indrrlcacclic acid 1 hc efTt•cl r+f in,lr+lcacctic :ICid t,n methyl gentsit and Irantfer his Illercfr,rt alal hccn invcclirated 1•7nrfinR.: Oit tcclit.ns nxidirc mcthiuninc tr, itc sulfnxide, h.,lh irt t•ivn in living and in hlrnu,Renired scctirms. '1he rc:rctir,n ic cctcnlially nr,n revertihle. Mctltir+ninc sulfnaidc can donate ilc methyl FNnrr ta rcclin and lo prt+tt+pcclin at well as trancfcr itc mclhyl grlmrs In nrcthir,ninc +vilh Ihe fnrmalinn (if mclhyl nrcthinninc. Mclhinninc culhrxitle c:lnnr,l, huwcvcr. serve as a methyl acceptor. '•MlifAllOI.ISM UI' NI('O11NL 10 ( I)(;AMMA-(1 1'YRIf)Y1.)- (7AMMA-MF.IIIYI.AMINO111r1YRI(' A(•II)" Ily ll/r+nrrtr MrKrN NIC, IA., I.rNN//7( 11. I I/ANN1111 ,,1nrl Ilt1WAA1, R IIr1WklAN, I)CI,.Ir1111CnI nf /'hannacnlrrpy, Medical (•rritc)'c Ir/ VirFini:l, ((i(hmttnrl /,rrnn,rl rr/ the rlmrrrrnrr (-hr•mmal Srhirlr•, Vrrt Rt/. I,:Ir.rt hS47 hMN), I)cc '/l, 1')SR ( I I R(' pr;inttt I)r P S I artrrn) 1'nrlrnrr nJ .tNFrr: In a f,tevir+ut cr+mrttnnicati„n fmnl thit I:,hr,r:la,ry, tl.ita were preccntrvl trs thnw Ifurl /•amma O I,yrirlylI-)(:Innna nn•Ihyi:rnl- imrhutyric acirl ariact rlnring Iht• nrct:rlruhcm r+f nicntine in Ihc ch'r, antht•n- Iic:rlinR in far/ n frnt•r:ll hyf,rrlh, tit:,I rnnte for tuth mct:rhrrlicn, ( Inlhcr slorly rrf Ihc thcmic.rl rc:ntu,nc .rml t,rl,.tantcc franrcrl w:lc n<•ccccary In .1 fullcr Irn,IcrN:rn,l,nl• nf Ilu• mr•I.J,.•L, I•rr,r r t. I'rnrrrfrrrr.: I+•Ilr,+.in/•. rnlr.n~ n..u•. r0 rrrrnnrrni-m ru+•dinr• (11. thc nrine rrf it nLhlrl 1. - 1,11 ' rrr.l Ilr, n I,I ,r i rl rrn r r rrlrrrnn wl,it II rcliinetl all K,nnr(• 1nr.,/,tr rrr,thrr•Il rlri.„i.rl ++.r. rrunrtrrl hv rlulir,n wilh N/I ammnnia ,.:,It•r :In,l .cf+n.,lrrl ml...r1 i,rnct Irl+••n f+.,lar rl,rrrn,.i- Inr.r:,f,hy with :rrurnrmia clh.nv•I hulenr•I llhc ir•nct al+.cnl Irlnn cr'nUul urine. were t'tanharcJ h,r f,r+cllrnn I+y t+rt/nnrnatrrl•r.,hhy w,lh nitr,linc anrl a numher nf itt elcrivativec; the m:ucrill at Rf 1/ It wac g:lrnm:t 1/+ylidyf- gamrna-rnelhyfhrn,inr+F,ulyric acid (11 ) NitlHinc, ct+tininc and unknrrwn at Rf 1/.61 were c>ttraclcd and the cr+nlrinncnt at Rf (/,15 ret:uned (V 2^:• t,r Ihe adminicttrrd dlrct nf nicnline /On hcaling. this m:der611 rccanlc chlut/, hnm solnhle anrl chanRed in Rf v:lluc tn Ih:ll r+f t'r+tinint, Icadinr Irt une- yuivncal chcmicil il/cnlificilinn F'7nrllnR.: C:Imma (1.Pyridyl) r-:nnma mclhyl:unimrhulyric at'irl, in the tnclahrrlitm nI nictdinc, ic nn rnrrnul rrnundc Irrrtll a prccuran :Ind mcl:lf.u. lite 1.f entininc it wat rlhccrvcd (rcyncntly Ih:ll nldcr t:nnrlcs r+f Inirrc crm tained inertacinply Ltu)•e atnramle r+l m:,rcrial in tllc t'nlininc rr+ne nf clnr, m:ltr+pramc and int rcatin/•ly cn+:rllc•r cr+nt t•ntratirmt r+f 11 I Ihit .Inmlan, nut I:u'finli~alir,n ic in :,prrenlcnl wilh tht• r.rt•virurdy n,ricrl inelit,ility rrf Ihe cnnlfwwnd Irtt•y+rttrvc td Ihe initi:rl Inr•rlr rd ilc furnnlir,n, a+n,r II will ccrvc as a I+rctrntr•r nf trrlininc in Ilhc 1•inln/•it:rl tyclunrt ttuJird II it I,nthrr cr+nrhrrlcd Ih:,l .rny Airt•tI r„nvt•rtirm rrf ir•lininr tr+ 11 wnnlrd rlrl+rml rrl+r,n 111r• Iqrtrnr t- rd .,n t'nivrmrlir tv,trur 1.I•.rrrrnrnl. in ,.Irir Ir r r•rinr,rrr. ~nl,l.lrr•I Irr Iln .,n.,n.,I ina+.,il yd n,r r.lirr.nreV •rrvr 1++ elucidatt the fx+scihle rale of cotinine as an intermediate in the melaFx,lism of nicotine. "A ('ONSTANI-RA-ffi INFI)SION APPARATUS." fly UIrFNTIN S. Mr'- KpNNB, f.DWAAr, R. IInWMAN, and (IHnRF11T M('KrNNIS, lR., I)frarlment of Pharnlacnh+gy, Medical ('tlllcge of Virsinia, Richmond. ToaicnfoRy onJ Applird /'hernracrrlnRy, Vol. I, pages 61-64, January 1959. (T.I.R.C. grantee: Dr. P. S Larsnn) In the cnurce of studies in which dogs were given aqueous snlulinns of nicotine inlravenoucly over an R-hnur Ixriod, it was desirable to develop- a moderately priced apparatus for simultanann infusion al cnnqant rate to si>c or more animals. '1 he wide range of applicability of the simple device developed for Ihis purlxse prompted a re(+rrrt on it. "fIIE IIACf1:RIAL UXIUATIUN OF NI('(711Nf?. I. NI(Y)T1NIi OX- 11)AIIUN NY CEil.l.-fRla; PR[:PARATIUNS. II. Tllli ISOLATION UF 11IE FIRSI' UXII)ATIVIi PRUI)U('f' AND fIS IhI:Nl'lhl('A- TION AS (1 )-6 11YURUXYNIC'OTINE." Bp L. I. Hrrr'rrsTrtN ancf Srn- Nrr C. R/trrNnrran, 1)tpartment of Ilacterinh+gy, llniver.ily of Southern ('alif.rrnia, IArs AnRcIts lmnnnl of RinGrRiral (•hcmitny, Vol. 234. pagcs 15 1 155 nnd 116- 1(+11, lanunry 1459. (-1•.1 R C. granlee: Ri/atnherR ) /'Nrfrn.e ../ .rn,ry: Varit,us pathways have been f.rtdulaled fnr nirnlint dep•radatilln involving an initial allack at eilher the pyridine or the pyrrnli- ,line rings. In an ennrl to avoid Ihe diaicultiet inherent in the use r/f clan- rlex sydcnls, stwlies c,f nicotine melahnlitm were attenrplcd at Ihe en?ymt level cmplnying crude and fraclionated e>tlracls derivcd from a hacterinm. Identifrcatitm td the first meWFwrlile itolaled cunlinued Ihe slutly. Proc.•durp: A Fram neRalive nxl istdaled fn/m toil and capable nf using nicntine as ils sl,le st+urce of carlwln was Rrnwn in a n+cdiunl containing trace salls, nicutine, yeast e.trict, and rlthcr trmpttmds. 'I he ima'ulated medium was Irealed with sterile air at rtxlm temperature, and the cutlurc was harvestcd aflcr it reachcd the ma.imum stnlit,nory phasc. tlllravinlel ahcnrplinn sfa•ctra nl cell free e.uacls were dtlermintd, and oxylten can. sumrition and car)w,n dioxide I+rtductinn were measured. F'lnrllnRa: Nicntine oxidation proceeded lhrouRh a serics of sharp changes of rale nc•curing after the uptake r.f 0.5, or muhiPle" of (/.S, pmnle nf t/>tygcn per rntnle of nicotine. Each pnint of change of rate coincided with the Icrnrorary accumulatinn nf inlermediales in Ihe nxidatinn ae- yuence, and none of the serinlly accumulated intermediales are uxidired until their preclncnrs are e><hausled. lhe first o.idative prntluct nf nicotine degradation by Ihe snil hacterium was identified ns (I )-6-hydrtlraynicnlinc by cnmparisnn with a synlhesired cnmPlrund. "IyARK I:IXA'tI()N (NF ('O. IlY Sll('('UI.fNT 1.I'AVf?S: ('nNSf'R. VAtI(/N OF '1llf? 1)ARK FIXIif) ('(/- lINhFR 1)Il1RNAL ('(1NI)I TIONS" fly (i/r,nr:r KIrN1TARr nnd PAm SAIIMAN, 1)eparlrnenl t,f Itinchtmislry anA Nutrilinn. St hnnl td Medicine. I/nivereity t,f Srmlhern ('alifnrnia, I r+s Anp-clct I'Mru /'hydnf.rkv. Vld 11, payt•5 41N1 4111, Nn vcmtxr 195R. "I)ARK FIXA1ItIN (1F (•O hY T(111A('(Y) I FAVFS" Ily tarr~r:r K/rNtrArr, ('I vnl Nrlr r. nml PAlrl SAI rMAN. I'Irrnr r'lrvr r•l.rcr. VnI 14, L:tRct 171 127. M.nr h 1')ti') ( I I R 1• p.raMrc S:IIUnnn ) m SI tn r, +n -J

Purro.e o/ .Iudf..r AlthouRh earlier .tudies etron6ly .uitgest that dark fl.atron of CO hr nrcculenta and nr,n-.uccuknts is ubiquitoua, the nature of the biochem~cal rcaction. Involved ir rxot fully understood. Lcaves of the succulent drryophyllunr colyclnum S.lisb. and of the non-succulent Nlco- tlnla raAocun, were .tudkd concvrrently. Prprnfrrwl Random .ampka of the Ieaves of the foregoing plants wete placed respectively in an apparatus which permits eitpc~sure lo C"O, In total darkness for varying pericxfs, and identification of the labeled photo- synthetic and dark products was made on aliquota of 80% ethanol soluble fractions. Flr..lfnR.r Tobacco kaven have the ability to incor~c~rate C"O, in the dark Into aeveral organic and amino acids, identi&d by ~,aper chrornato- paphy Rnd rwdioautoRraphy. The Initial rate of dark fixatron In tobacco Is more rapid than that of the .ueeulent R. calyclnum, but the total amobnt of C"O, Axed by tobacco after e:tended periods Is much kss than by the aue- eulent Ieaves. No carbohydrates or phosphorylated sugars are labeled tter extended periods of dark e:posure, suggesting that light is needed to furni.h the .f+ecific power to reverse Rlycolytk prooesses. "Ol1ANTltATIVP, STUI)IfS UR SCOPOL@TIN IN C/(IARETTE SMOKR ANf) TOR/1(X'O." Py (.I/AOIIWA YANO, YASusrrt NARAOAwA, and S/MoN WrNora, Chemistry Departnxnt, University of Oklahoma. Nnrman. Analyrical ChrmMry, Vol. )1, pages 2041-2041. December 19SR. (T.I.R C. grantee: Wender) * Purpo.e o/.rrdyr f)iscovery that the mainstream smoke from ciRarettes commonly used in the United States contained acopoletin has necessitated the development of procedures in determine quantilatively the amount of this compound in the smoke and in the cigarette tobacco before nmokinR. Pro.wlur.r Cigarettes of 24 diRerenl hrands and sires were anatyred individually or In comprsite by smokinR on a standard smokinR apparatus, condensing the amoke in flacks, and by RrinrlinR the tohacco from ciRareltes with the filten and paper removed and extractirm on a steam hath. fkfer- mination of the acrnf+oletin content was mar7e by paper chromatography. Fi'nrflnR.r lhe amounts of scopolNin in micrograms per Rrim of tobacco ranrcd from 66 to 123 for reRular, menthol, f'ilter, and king cire ciRarettes, and fmm II to 4R fnr denkolinired cigarettes. The amountc of scopolelin recovered from smoke, in terms ot microRrams per Rranr r,f cigarette smoked ranged from 14 0 to 27.4 for rePJar, menthol and king sire ciRar- ftes, from 12.1 to 17.9 for filtrr ciRarettrs, and from 101 to 11.4 for denkotinired ciRarettes. A ciRnificant percentage of scopr+ktin pacsec IhrouRh the filtert of the filtrr ciFarrltes nrnlyred. (1rlh.r Rrnnrnrr Ahnnic I"nerpy ('nmmiccion V, O(Fevr Shrrler. "Mf'.f)IC/11. IISfiS OF TY)Iln('('O, PAST ANf) PRI'Sf NT." Ily 11 Stt.vritr, Pth I) , f'. S. I.AacnN, Ph 1)., anrl 11 It IIAA(t, M 1) , I)rirrrtmrnl of Ph.nnncr Ir ~y, Mrdicnl ('rdlrRc r f V irginia. Richrnnnd. 1'ir rirri,r Mrdi, nl Mnnrhlv, Vr,I RS, r.rrc 471 4R4, Srrtrmt•cr I')SR ('1 I 11 (' frrantre' tt1+r ) In this review of the literature, no attempt has been made to retovh' the earliest history of tobacco aa a drug. The year 182R haa been taken as the dividing line between the "ancknt" nd "modern" pharmacological history of tobacco, because nicotine was dlscovered by Posselt • Relmann in that year. Although tobacco is no kxtEer an oe4claf dru6, it still Is fte- quently used as a tolk-medicine, the authors report. A bibliography of 166 papers on the.ubject is appended. "Tobacco made its world-w/de conquests under guise of a dru6 " an epilogue to the study says. "But the dangers attendant upon ita ttler:peutk: use, as well as the discovery of aafer, +nnre efficacioua, and often more specific remedies for many of the diseases in which tobacco was once emplored, have taken Il.rpo Panacea out of the pharmacopoeiaa, and, indeed (in spite of more scientific theraPetltic tests by some rncxkrn phy- .icians). generally out of inedkal praetroe at well. Tobacco as a drug M now primarily of only medico-historkal interest. ~(h is it7 llave we not forgotten that most esscntial and charactetistk of all the pharmacoloRical - and hence therapeutk - properties of nko tine: Its unique bipha.k aellon on the hiRher, if not the highest nervous centers of man? Ilave we not forgotten that, by virtue of Ihis ertect, tobacco hae been used and cekhrated for over three ce.rturks as what we are now pleased to term a'tranquilizin6 drug - a'tranquilirer,' moreover, with perhaps a higher therapeutic Index ot safety and a lower incidence of dan- gerous side-reactions than any white tablet or colorful capsule similarly chronically used." "ST(11)II:S IN 1OBACCO HYPERSENSITIVITY. 111. REA(TIONS TO SKIN 7F.STS AND PF:RIPIIf?RAL JASCI)I.AR Rf?SPt)NSPS." fly VINfrNT J. f'ONTANA, M.D., WAt.TrR Rcnesctr, M.D., R(nr l.rr NlMIR, M.D., MARJ(Ntlr K. SMtT/t, M.D., KtrRT qrCarNts, M.D., and MARION H. Slrtzeraora, M.D., New York University Post•Ciraduate Medical School and New York University Research ScrrSce, ()oMwater Memorial Ilospital, New York University-Blellevue Medical Center, New York City. lournaf of AIIrrRy. Volume 30, pages 241-219. May-June 1959. (T.I.R.C. gran- tee: SulrherRer) Purpo.. of .trrdyr Tbe divergent views and findinRs in the literature on tohacco seneilivity prompted the further investiRation of the pocsibility that certain tobacco effects are based on a specific allergic susceptibility of par- ticular per.rros rather than on obligatorily toxic pnxlncts in tobacco snrrrke. Prnr.dNr.a: Skin reactions to tobacco eatracts were Iectcd on 641 heahhy adalls and 294 children Rnd hietorical data on the suhjrcts were colleclyd. '1'rrhaccn exlracts were prepartd frnrn Ilnrley. VirFinia and 'lbrk- ich cnred k+biccrn and from a blend, in equal parte, of the arhacco .nd parrr from ci>t principal hrands of eiRarellrs: two lyrec rd Ihe miced lo. h,eco e.trnctc were Ircted: one wns defnlled with tuluene before aquenuI rxtractinn, rrmr.vinR arrme organic cuhsinnces which miFht nct ns allrrRene; the r+lhrr wac nrrr ttratrd before e1lrAfti/rn. In a ut'wrJ r.prriment. R() hrnllhy adultc who had I+rcn ckin tcclcd wilh rrrhaccrr rctr:rct were stuJicd brfr+re smakinR a cifliarrlte and at vnrkd intrr vilc Ihrrritrrr, nn,l a srrirR nr carJirrvaccul:rr rnrACUrcmrntc were rrhtninrd FindinR.: AnumR the artultc. IR 4'::. rrf the amrrkere ahr,wrd markrdly

ra,sitive reiclitms tt) nne or more or the Inhaccn c>ttracts, cnmpired tn 11 R^ or Ihe m/n vnnken; the drRcrcncr w;)s nnt fllund tn he statisticalIy sip•nificant. '1 here were more "markeJ" rcaclilmt to Ihe nliled It.bacct) e.tract thal was not Jcfaltcd (9 R^ I than to thc dcfalted eatracl (f50';,. ). Sex Rn(1 age did not seem rn rlay any role in the incillcnce of 1he rrictiont to tobacco in Ihe varit/us Rrtlurs testctl peripheral vatcular symprtlms among 177 tmtlkers tested with Vir- Rinia tohaccn exlract were aboul twice as common ( 20 to 1(1 % cnrnpired with I I In t S? ) in vnokers with positive skin lesrs than in smnkerc with negative skin reicti</ns. In 200 non sntnkers, the incidence of these symp- loms was afa•nt the samc (10 to 19^'r enmrared with I I to 14% , respec- tively) whether the skin test reaction to tnhaccn was prnitive or ncRalive. In the Rrnup of sn+/)kers with a personal history of allerpic manifesta- tions, SJ 5% were rnund tn react )+lwitively to one or more of the tobacco e(fr.cb. In ct/nerast, only IR.7^ of the smokers without history of allergy reacted tt) Inhacco extract Among nnn-smnkers, the fipures were 40 9'"i, and 14,7:n resl.cclively for Ihnse with an(I wilhrnu l.erannal :111erpic his- Glries lhe skin scntitivity to Inhaccn crnlllt wcll l.e rnnrt readily aclluitrll hy the Rcnrrilly .Ilt•rpic I•ent)n Ihin hy thc penerally less allcrFie nne nn imimate r/r cnsuml cnntact with klhaccn smnke Rnd prlKluctt. No significanl diflt'rences were frvrnd in electrllcirrlinprapflic, hillisln- cardinp(aphic, and hLM,d flow meisurement chanRes after smnkinP. On Ihe other hanJ, skin lemreralure chinRes were noted in 2R7 of the smt,k- ers giving positive skin teat reactinns to tnhaccn and in only frlur per ceni of those ~.ivinR neparive reictirlnt -lhe diflcrence ic atatitticalfy sipnificint. Of Ilie 294 chilllren apcll Iine rll five years skin testt•J, I 1 5'":, rcicrcd rotitively to tme or ml+re tlf thc ttlhilt-n e[trac-Is Oucstinninp or Ihr pir<nts or 2(.9 or Ihe chilrlrrn rcvealc/l no evillcnrr of atlrrpic manifest;llirrnc; or Ihese, si>t (~r cent re:)cted faltilivcly In It.h,cctl e[tr:xl Of the 2S cllilllren fnund In he allergic, Ir4',",. have evillence Iif skin sensitivity to Itlhaccr+ Practically all the children were er<rxncd tn one or m.rcr sml+kem within Ihc irnmediile family al hllrne 711ere were nn apc or srR Ilillerencrs. On the hasit or tht•ce fimlinRs, there is a snppcstilm that the skin tru with Irlhaccn may f.c hclpful as :1 "s('rcrninR" trst tn aid in rlcterrnininp the possible imra.rtrnce of Illhiccn at an ctild/)Fical factllr in certain fllrrns or peripheral vascrllar sym111rlmatolrlpy. FnllnwinR are litlcs or abstracts that appeared in the 1957 and 195R Reralrls tlf (he Scientific f)ireclor: "(ARI71At' Fr1F('t5 or INTRAt'ORt)NARY ARTFPIAI. IN1F('flONS OF N/('O 11Nti " ny l.Mre w. Wr.r, R S, S.wrl..rn V. M I). and S.MI/rl Pr/ r rr. M 1), 1Mp•rln.rr.l .4 /•h.rm•rr.InR7, t/ni.traily rd t•rnn.y/.•ni. Ar1rv1 of Mrdirinr •nd Ih.ifi••n of t srdw•l.rtt, 1'h.ladrlp hi. Urnrr•1 Iluy~./a/, 1'hll•drlphib, P.. (Mrrf.ra.n R.vorA, Vol 6, No !, p+•Re. lto 193. A1.) l; tt. (t R.(:. Rr•nlre: Ilttkl' "t f)NtPr(III IIY ANU FXIRACTAn11ItY (H' 1/1'ART A(ZnMYt)SIN AFTFR DFA t t/ " R7 1. Derrl r, M 1) and R. 1 Rnw. M t), 1)rp•rlnrnr of F.Perwnrnl.t M.dlcine, Ihe Mtdicd ('.41rte of A(•h•ms, PHTinahsn\- ( brr/IIAM Rt.r.rrA, Vol. 16, Nn, S, p,art Sts 122. Sr(wemhrr I6 "t t7N1RA(lIl I: 1'R(IPIiRH6TIFS OF A(TUMY(1SIN TIIRFADS AND BANDS rRPrARfl) I RbM t)t1/:S' /1t''.ARIS" Sr L. Ihtnr, M.11., and P), saro, M t) Anrrrl..n Inrr.n,d nJ PAyrMrloer, Vnl 107. No. 1, oars 145-150, t)trnlvr 1956 "1-/11r-t t)f(lt7APt IlF SMt)KIN4: (IN ( UPtINAPY RtO/1D I IOW ANI) MY(L ('APl/lh(- MF1AM)I ISM." R) L. M. S..na.nw, /., M11, 1) FM.rar. M1), F. (inrr- M.I1, A('.srrnr.rrm, M1), A. Srrrlrr, M1), and P. 1. Rnw, MI) (Y.r~l.rlnn, V.d It, Nn 7, psre. 751717, r.hnur7 1957. "IHA(iNOSllt' VAI l/f' Of At fIVtTY OF MAI IC t•F.IIYDP(J[:FNASF ANt) 1'11t)t. 1•1111111:Xr/S1: 1S(/MFPASf: Ihrbrwin.rr Pr/~ntH of /indinas In PalirnH alh M7or.rdi•I In/nrlM.n •nd Ii.rr 1b.r.v" 11) Rrrnae ) 11rnn, M1), Al.r.)o t'•trrrl.w.q, M17, and A.•.nur Srrr.rr, M A, /nrrn.l of rAr An.rrk.n Aftl4.l Anra4rA.n, lune a. 1117, r;p•ar. b•7 6%n "IN t1 PMINATtONt OF hPN (TPNI TItIAMINP- AMtNO ACIDS ANI) AMINO SU(:APS IN /11(K11) tll ANIMAI S WIf111 XPIPIMiNIAt. MYIN APDIAI. IN/APt'l It/N " n7 (I t..•ru, M 1), A PrvrAr, M 1). ond R. 1 Srrro, M 1), I)ep•r/menr nf Mrdl ci.r, W•.hinalnn I/ni.rr.Ny Scho.d n( Medkine. Sr I oait, Mn (Hr.rl.rlnn Rr.r•rrh, Vn1 6, Nn I, p•srs 15 I9, lanu•.' 195/1 "MFTAR(HIC STI/DIFC ON T11P- ARRP-STP.D ANI) FISRIt.1.ATtN(I PPRFUSPI) 1 IIIAR I" Rr Auu,e Rrvr/., M t/ Cruu rs Sr.saf, MO, and Rn n.•n I Rrrrn. M 1), / A(-(' Anrrrl.nn InNIINf nf (.rJJoRt• Vol 1, No I,pae. 10l112. l.nu.r) I~Sa "(UNTRA('T11.IIY (// A(IUMYO5IN SANI)S PRfl'ARFI) FROM NI)RMA1. AND FAII IN(: IIIIMAN IffARIS'• Ry K. Kato .nd R 1. Rnrn•. lmren+/ n/ ( tlnlr.l Inrt.rle.. Non, Vol )7, Nn, 1, p•te. 461 1717, MarrA 1950 (T.1 R.C, {unler: RinR) "A StIRV/?Y or (I/MPOUNUS Ft1R A('lIV1lY IN Ttlp SUtFRFSCt(1N OF Mt)tISF. SI-RA(1OtIS GIANI)S" R7 1•rn (i. Srna and Rnm. Mlnw, Ro-etl (.rk Mtmnrid Inalilulr, Rul(.to, N Y. l.rnrr Rrv..rA, V.4 tt, Nn- R p~t. RR/ M2. 4Olrrnhrr IoSR "('AR('INlK71NI(A(IIVIfY O1t'I(iARF.ll/i SI~OKI'. ('(INt)PNSAtF I Itlrct nf lr.orna anrl Rtmu/r X Irr•dialion" R7 Ir.n (i P..rt .nd (i.rNn1 H Mnrwr, Rn.wrtl Puk htrmraiat Imlilldr, Pufl.lo N Y lrrn..f of tA' N.r4r..d (.nerr lw.rlmrr. Vul 22, No t, p•Itca 4111 412. 1 rhnr•ry tslisa (T.1 R(' Rlaerre: Pnc1) -•t IIAN(IfS 1/f: POI)Y WIi1Gt1f IN NORMA1. MFN WtIQ STOP SMl)KIN(i ('I(3AR. ..rdn.' of PA7.{nMtir.l 11', ienr, School of 1'uhlir 1I'11 t" R2 I R•r,r.a •nd A K.rt- I L 11.•t/h, llnr.rrul) nf Mmnrcou, Minnt•n•d'n Crlrnrt, la[R 14, 1951, P•ae 1701 11 1 P(' RranlYr:nn..rk) "NU( I l~lt' A( 11) Ml TFPNS 1)ItRINI) (IROWTII AN1) PFGRPSSION OF TIIF. MtIRPIlY StI/RM I YMI•11()SAP(Y1MA IN 1/1F RAT." Py 1 Pnrrwn R( r.er rar and I nw..u P.r.r.r.., Ilrrartmrnl n( nirwMrniar/ fr.rd/h.m Itrmrrrrilr, Ne. Yors. R4rrM.w. l.• er Rr••pA Jr. Ar.. Vd. 21, Nn t, p.Re JI76, ).nu•a~ 1977. "tII1M1(A~ ('IIANta'.S IN ItIN IttNGS l)111tM1/P IIRAR/NO RATS" Pr trrlrrMn R(r•rrrtn, /nw.•n O•r.wna, 11.•.• tLrw.r•.w., Iletrlt L. Rrw.arnr.[. Fnw..n 1 Guu•r.r, n•t tnw.•n I S/rr.e•, .NA Ihe rrw~.rr•IM.n nf VIN/rMr S f•.Itu.n.o, //rr•a.rmrnr nf 1•alhrAnal, MraJo.hrnn\ 11r..pU•1, IIrn.P.Ir.d, 1 nn' tJ•nd Nr. Ym1 Rbrrhn nn rr RA•rAru.n Arr.. Vol N, Ne 1, P.arr VI 61, April 1•/7 11 1`l t' snntrtr rlrrrA..) "I l lf( !(IP f'I(7AR1-TlF SMOKINI: ON (iAC1Rtt' SF('RFTtUNS t1(' PAl1F:Ntt W1111 I)111)1WNA1. III/1.R" 97 t'nule (r.rrrll, MD, A.v.ci•le r.nfr+.n. uf (-1{ni trl CurF rr7• Rnu..n Um.rrailr Srhrrd r4 Medi.ine; th4f, Suralcat Srnicr. nd rlfreNr.m, Curaa•1 Pra•nA 1•Lr.r~l..rr. VHrr•r.. Adnrinidralwm 11n.pilal, Rro•iJente, PMnlt td•nd, •nd l.ur. P Ka«wr, /• , M 1), Pr.Mknr in Crupr7, Vr/rranm Adrninial.•liwrn slnqal•1 1•rnadnn r•wd M.a.~. hnx/la Mrnwwi.l Ilnapird., Rrraun, M•..a h1.a11., Nrr I nel.n,i I.rr.rnrl n/ 1lfednnrr, )utr S Ilt6, p•ft 17 21 "1/sYtt /11' lt(:ARt t-IF SMUKIN(7 t)N 1'X( RI1tt1N (IF URl)PPPSIN ANt) tY1N (/ NTRA11ON 1)1 PI ASMA Pt PSINtR71 N" IN Prnrre fr.vr.. M tl, 11.•,nn I ttr/a, MI1, t:rnn.N / Mr.•.., PS, aml W Il...nwr.. Mtl, RA•.Jr hl.nd AIrJ..d Vnl ul, Nn 4, r••aer 711 )1& A 7t1, Apri1 1911. "11/ Ft / 01 l I(;API 111' CMr)K1N(l ON 1111,Ct)1 V11) t7ASfR1(' R11r(IN[ ANI) VlStt/\IIY t/t IUC1N11 11I1(/ ° Pr /rrurr t...rr•, M/), ~rlrr.m Ad.u •11, nl..• 1. n- 1'r••r...... .w•r 1 A.I,n , Ir.r•.,r.nr••. ,•/ Mr.11,Mr, wrr r~r.r. Lnl.rr• r 1..Ir.t• ,.1 M.•I,.,,,r, I.r.•.•1., MI,A 1 54 SS

11r..riUl, Rrnn., N Y,.nA ( Gnir.l rrr•rr+anr nf Su..rr' AIMrI hir,alrin ('r•Ilrnr nf Mr,b<,nr, Nrr Y,•rl \u v. M 11, Il..,.r n W~ Ilcu,•wr• M 1, Vr,n.n. Adn .Irnn IA,.(.nal, 1•,n..,lrnu. R 1. nd Il..a.«, I/,u.rrvr) nf C,b~«.t nf AlrJnu~r. IL.a1n.,,rM. r•.I Il...r,rrl. 11 Pnr.r. A H V./n.n+ Admn,nalr..h.,n 1h„ra.l. drnrr, R/, c:n .n.nrr.nfnr). V,J 1). No. 6. paRr+ 9t9 9(•7. f M<rmhrr tvS) ,•i "111P Il/lt I frl~ (II:ARI tI! CM/)KIN(: /IN INIMAI;A\IRIt" RAII(HIN rR/C SIIMP ANf) 7I MP/ RA71/RP. (ll rA111 NIC W1f /1 Ult(/11! NAI. 1/11 1R "' Rr rrr„rr ri Atl/ Il.a.,rr. w M I). n I C,rr«, AI U , .nd p S Vnt1S, Nn 2, r+p, I161t7. A„t,ra 19+t1 1 1 I R(, 'ranlrr (,v.fvr / 'hR/ CCl/q/: V1/1 I/Ml ( IIAN(~F~C IN Tltf 1(1R/-ARA( VI INS f/l~ MAN /)UPIN(' IIV/•IHVI N11! AIIUN" Rr h•«« W Irvrr«, N'urru, K Il...nln« wn•t 1••n« M11, Mrl Ilrpa,lmn,r, ,.( l,nnnal Mr.l ~ rcmr an•1 CnrR.rr, %I.Ir I/n,.rr.rlT nl In. (nltr[r n( Med4inr, to-., I A7. lnwrn.l of (71wl.wf In..nltwr6,n, Vn1 17, Nn 7, rarr/ 9tA 9AI lul' 19111 I R( mlrt/ alnrinl "tMM17N1)I(M;1(AII I ACrll .r1S O/~ tI1M(('tl ANO CK/l)KIN(;" tl) II SN.rrrr, rlrr), rs 1u.n« rn1/, .m1 It P Ilun M11, /MPa,lmrnl n) 1•harmranl••.., Mr,L,.l ( ,•Ilete nf V/r.ini.,Rk Amnml Aw,rrN.n /,•,nww1 r/ rAr Afr.b, wl Sr rrnrrr, V,•I 71t. Nn a raAre MI 119, Nn.rmMr 1951 111RC pranletIIa.R) ~ "IN/YIRfN(IC tI1- IWI/N SM(7KI~RS ANI) Nt)N CMOKFRC" R7 Ct. W/lr.rn. Atl), /lealh Crr.i,r+" Iln.,rd t/ni.rnat. (-.mhrNl~r, Mna+ AA/A ArcA„rr n/ Iwn,«nl ALJ«Ir.r Vri Inl. Nn. 1. rqr. t/I tR11, IrMlmr' 19111 "NI11 F(/1 1)!1 IARV / AI IN tI1/MAN N1/1MI I11)N 111 f)/1 I ANl1 Tllf 1 r11/1 k/t 1111N;Y I/I !/1RIINARV III AR I t11\! A\I Mr A«.rr Kr.a. Pn 11, ! AI•11A, an,l /..« I lv.. 1:..«w. At !/ t a/.•r.dorr n( 1'l, u,.l,..l, al 11/.«rv. I lm..rvq n( Al,mv.nla Almne wp.,h. .(,..r,awn 1.•..r.... I •I Vr.l 41 Nw 12. F,.r. 1+7(1 ISln, //rumMr Ivtt I CCUNC I RfIM CIPI'M t/1t/11 C11 P111 C11'l/l C IN )AI•AN, IIAWAII ANII 1 UC AN/;IIIC" n) A«rrl kr... rn1), an.1 M.u..e.r 11c«re Kr.,, t9tr ~. M,nnerr,•1:.. Al,nn: Nr,a•wu A11l.nr1 Au. M/1. P R.n«rr[rr».r M I/ ,//.for•1, I~nrL,nd .nJ Nn . 1.,r «. 1~ 1) ,/ At r, Ilnn,d,Jn• I/1 Adr ..l L,rr.«wl Alrlr.l..., V..1 44. N., 1, p.a.r+ /lt 94. )rnll.nl 19+/1 11 1 M( /ranlrr Kr/./ "(:AMMA - 111•S"RII1Y1 1 .(;AMMA A11 1115'1 AAIIN/)nU11R1/A( Itl AC A IrMI NARY M/"IAnr)1111~ (/l N!(/)IINI- H. 11r.wr.u A1.Kr««r+, ). Ir««,,. R ll,.rr ,•Ir,.n,llnr..nM n••.....« 1)rt.a,lmrn/,•frhnm.,,,,h•r),MrJ{,.11nl,rrrnfVi,R,n.. R.chmr.r„/ l,•r,r.... .l rbr L.,r.r..,.. 1 I,...... .,/ Vot )V 1, 19t] • . r.rr+ R11161tt, I)rrrn,/vr "MI: JAROI llfC or NI( IIIINF ANi/ A fVN/11Pqt (1/- NOR NIt()TINF " Ry Ilr..ra AIrK/««ra. /r, 1r-««n, n lu.«wn,l Il...r. N Wr«..IUIq /.. .nd 1nrr,r I 1)rwf• 1,•n••,.,! ,./ rh. 1«...r,n« ( Ar..... .rl ,C,•,r.rr. 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Inlr,n,1r, t r~nlr., 1, „rn A,I.,. V,.1 /S, N~n 1 . r,rr: 617 619. 1vtN /1 1 M/ ~.anlrr: ( c,Arr 1 ru,h/n,Mr~r.Ir "Illt P[Y( IIr11/Y 111CA/1/K1N1;" Rr I n.uc+ M,A.rn,-r. Illr« W.rnrr,« ,nJ )nrr« nnr«+..«, n.arh Crr.,,.a tl,r•„J 1'rr:..,.,/,. 1,n,l.r,rl/.. A(.... Jn«.,.nr n) .IA «• ••rnl nnA S,rb.l V,J aA, Nu 7. /•.•rra 2A1 71a AL,,,A lYtt 11 I M 1 .r.rqrr- M.Arl/v,r1 ' '1VAll'AIIIIN(1I CIIRCIAN//CrAtrCINl;1rIC\c)1 C/II~(IIIIIC(;1ANI1C1N/11.1 M111'\1- CKIN" nr 1.rrr (; /6«., A1 C. ..r„1 1/n,./.. A1n«r• RC, P,•,.rlI 1'..\ Alrr,.••„d ln.ranlr 16,f1,1., Nrw Y••r1 7........ I .•/ I,.. ,r,, I•..rr•.rr.•V.•1 7h No A 1•,.. .)91t1, h ,r n tva(. I11H1 r „otrr / . . . "( I(;AM/11/ CAl/)K1 IICll/lf 1 IrN I•t-IM11NAMV II- N( 111)N MI ACI'RI M1N1C"" nc 11,1 LL,rrre A/ll „r,l ISu,rcu I Kr-..a.« k/tl, /-h- Rral.:,alnr. .,L1.rrn,r \,1««-1 n/ inr I,•. Anr,lr. f nI.I.•••„w Af.,l\'.•I . 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SoR 517, Winrrt 1111,10, 1 f 1 R(' p.nlec Mi.,Mn/ "1I1//)ARK I 17(A I IUN OF (()' RY C1/C('111 FNT I FAVFS: MFTAROI It' ( IIANGFC SIIt1C/1)111NI 11) INII/A-1. fll(AT1t/N° Ry Pun Sa11.r.M, Vwllo/• 11 1.«rn. l:r.r,a AI Kn«Ir..r. lrtnc Culc .rN11b..ru \r,nrr, 11eparlnwnl nl Rinchr.eiall) ald N«un.,n, C, I«r.J .4 Mrdia inr, l/ni.ereit/ nf SarWhrtn ('dil.nni., ( ne AnRClr. Pbnl PAIV.•1 12. N„ 1 P:,4e. 197 ?1f1 M.11 I9S7. 11.1 R(' p.nlre: Callm.nl "M111) 1I1' NAII /1! I:INl:IVAI. Fr11i1111M IN IW/) A(:/: (:R(11/1'S" Ry Irnr. RC, Au.r«r C ALwur, RI)S,.nJ InvrN P. W./«M.HN, MIT, 1)~.IdY.n nf /1,a1/'a/h••k.fr. I/m•rr.n) nt 1111nru+ 4 rrlltle d(Mnnap7, (hkap ./onrn./ n/ InarcrlR wlhr ll.ro.,o..h•er. Vd 71, No 1, pqr. 211 2N7, IknJ,e/ Na6 IT 1 R('. Rr.nlrr: 1 ScMrwl "VI Nttl A1111N IN ( IIMIINI( rl// MI/NARY FM/•//YCFMA 1. rrteeule Vnlnrc.r nd 1•.r.aurr I h,r Mrr.n1,q•. II 4 nr. rlalinn ..I t.nnrhanrr nnJ Mrthnni4.1 Kevd.nre WrUr Mnnl,ne I'Nbn•,n.nr INmli„n Iral." R/ I-1.ac 1) Aclpa:r, Mr..ul M GI•In.rrl«, and M.u.N• S\rau, I)rp.uln,eo/ nf Mrdicine, lofN Ilnlvrldl) tchord n/ Mrd'N/nt, t1..ann. Maaaa.h,wn. .Ln.r«rw Rr.l.rn/ 1«Arrrr.L.dr .n1 I'rdnr.•nn.r 1)rvw.rr, Vnl /4, 1 N.• 7, ryRr, 2111 219 .nd 22tt 22I1, M.RNCI NSA "1 11-t ( IS /)1- tM/1K 1N(7 1/1'r/N 11119 MI:( IIANI( S OF /IRFA 1111N(i " I In Nnrma/ Cul•/r,la 1t In Parrr,n. .,.h c arJuy.ulm,.nar. 1)iva.r" Ilr 1.«v1/ Arlr«ar., Me.u/l M•rMI MNnnr S Crc.r. )Ar A«.r.NOC Rr.Mr n/ TrrArrrnh.rl, nnA faL •• rwn Ihlrnv., Vol 77, Nn 1, paRe. 19 and 11/ IA, )amnr) 19y 11 I R(', .canler SrR .11 "IA/MfllfAlF. IIIfIT M' (IIEWIN(; TOPACCO ON ('IRCI)(A110N OF IIARII IIA1 I IIIWI RS" 11) Ucvm I SIYIw, MI1, A«IMn Imatun, MI), lnnrr R. R..un vrr«, M I), .n,l R,•tlwt I~ R..rl. (.r,riaa' .nAyldnry, Ikpalmrnt of IMtroal M.Jnlnr, ("incinn,li (7rnrral Ih.ap:lal and Krl/rrinip I at.nralra), llnlrrr.il) nf ('inrinnwlJ 116in /.•«..,.d nJ rAr A.•rrrr•,,.r At.Jr„d Ar..'r4rw.n, /eMuar) 2. 1131, P.Re. 1SA.1SA 1~ t R('. /raatrr: 6'rnnnl "CI)l l/Rl h I IVFR h rR(I11'INS hIIRINO IIFMT(1CARCIN(x;t'NFCIS RY AMINO A71/ IIY/ S ANt) 2 A( I 1 V1 AMINl/1I1r(1RF11F IN T11F RAT." P/ ta.r Crnnr, 1•n/e A/. Y«r,«,:, anA M.ul.r. (3 (/ft, Inatiluor fue l'anrrr Rrvarch nJ I.nlrn.N Iloy.:lal Re.raah Inab/u/e, 1•haadrlPhi., Ptnm~I:anl. (...rtr RnrurA, Vnl 10, Nn I, pacr, 1144. )anlur) 19S/1" (1 1 R l uMte' SIN..) °( IIARAt'/.R/:TIt3 O/~ 111F INUSVII1l1A1. AS (1JI1)FrOSTS T// T/11'. PRFV('N 11UN (11' Il1AM1 111C!'ACI~." Rt (an.r/wr RrrM/l THnwaf. M11, 1A( P, Aaa,rl.lr 1•r,Arww nl Mrd«i•.r. 1r•hn. //nplim llni.era.q• ScMw,I of Mtdiclnr, ILUimuce, MI) Annnl, r,/ Intr.nwf AlrJwrnr, Vnl ell, No 1, raRN 1A9oln1, Stplrmhrr 1951 "I AM111A1. ANI/ P1•1111MI(Il(/(;t(' ACPIft IS (11' (ORl)NARY I)ISI:ACI' ANO IIY1111411 NC1/1N " Rr 1...n /«r R.Iwr r IrN,.r... M 11. /.«rrw.f n/ ( A.un/r Nrvw.rr. Vrl 7. Nn 1, palr'a Ive 1oR, A/:,r,h 19SR, •'/1h (IR( 111 AIURY MI CP/INSI1!) SMt/KINI: T11F VARIAI1/1N IN nA1/1C1t1 ("ARI)IIM:RAr111(' CMI)KIN(i l1~STS IN 11FALTIIY VUIIN(i MFN" fly t Il/lnll Iww.a, 1,111 anJ t oM„«r. A M1'arN.. R1 1 /nr,.nwt ../ ( h.,•wa fNvwvr V,J 11, N„ 2 r.rra !n7 17V. A,vuU 19111 11 ! R('. p.n/rr Ihnmaa) •'1111N/111t AIt//N (H Gnt•111F(IN IN 1'1(3ARF11111)RA(("11 ANI) CM(IKF'n/ /u.u 11wa Ya«n, Va+uun 1) WtMIN., IIr(,A1/mrhl nf 1 Mrn.a 1,), Iln:.rr.dt nf UI1,/„•nr., N,um.n. Jn«rnwf n/ //.tnnr. ( Ar«dv.r, Vd 21, Nn 7 IV+11 p~na 7M 7nt / rLnrnv "I II/tA1A1111N tll Cl')1•IH 1 IIN I RIIM 1°C11/11N ANf) FC( 1)11'lIN IN 1111' PAf ' /1r l N.r, 11w• Y.«,i, 11 11 Ru..ar P. 1. M R Snrn a •n,l C 11 Wr«nr. (.,Anrr.•1I1,..,lrr,.,.•... .r•.111«,t.Alr«r. V,•1 74. N„ 7.1•:,.ra S•nS19, )nnr Ivtlt "C1/11'1/11 11N IN 111MA/1 RI lA1 Ic111A(1/1 1'R(11/1'/ IC" R) l/lw• Y.«,. V.vr.nl N...r..w. nd C,u,w 11 W.«w. Vnl 1, r.,p. I/t 11. A„r„al 7•. I9at /1 I'H 1 /r.nlrr WrnJrrl °\nM! \IA11\11/ At r1R\I IIVAIIIINC /IN A(il(/r/ RA1IV1 C111IrY III /111MAN 1'1'IMrr1JANV 1'A1111/1/N,V" Ilr I w,• ,r• P Nrr.••r. wnJ A1.. 11 h,ur L,•....L.,r, „/ rh. N„rl I,.rJ....• •.I Vr.l 41 . 1•rrra tn/l 1/,I11 11.,r,n/vr. latl. w,l ~. C(, t7 n Oa B

IrnrrrlGrr n/ rM N.rbn.1 Ardrn.r o, Srlrwrrr, Vol. 41, p.lr. 111V 191. Mvah 1•10 11 1 R((r.nlrr t'vh,•1••1ir An.rornktrudrl CI)MPARAIIVr: VASrM /)NStR/( I(/N r-/I1( iC (IF INIIAI IN(; rOPA( ('t) CMItKF IN WARM ANI) ( UU1 I NVIN(tNMI NIS ANt) RI 1 110F ANt) A/ 11 R APV INI N( I IN()M 1(/RA((1)'nt )rnrn W. Fr.a/.n., MI/., 1 Innnr W,.re. M 1), and N,....u W Wn.wt, M IJ., (.rdn....ruI.r F..nr MrmI41.t L Maa..<Auvl/a l;rnn.l /6npi. 1.1., .nd Ihr 14p.rrrnrnl .f Med:,ine. Pn.t..n Uni.rraN) S(Md of h/edninr An.rnrrn 11..rr lnr.nel, Vnt ./ Nn 1 pnRe, 4~14A1, M.rrh Ia47 "t-/ /l( I/I1 ((N)I.IN(i ANh III CMt)KIN(; (/)RA(( 1) 11PON 111F PI(1(7(, 11(1W (/( RIAt11VF /1)1'FNIMIA e)/11r/? R7 /.r 1) I.,rr...w, Mlr, 1/nwrr. W+*'++. M 1), .n.t P.....r W Wn ar«r, M 1/ ( brol.rMn, Vnl It, No 2. p.Rr. 17/ 102, Au.wr 11a11 I I I R( p.nrrrWrr.d) . I I Recipients of Grants FnllowinR ik a litl of all recipienta of granta approved by the Scientific Advistlry lklard -.ince initial Rranh were made in lete 1954. It shr)uk1 be noted that some of the projectt have been completed. GItAMTF.F. AW// IN45T'ITIrTt(1N PROJE(T TIT1.F. I"C" ..r.....r r.a.n r...M.wd: ..r' i.A-r . ..o.n .. -«L Lr t.... HIr(4.tf ( 1 ARI'NC'F M A(7R1'SS, M 1), C'Aic/, ('nr,bnr•nu rdnr I aharnrnry, Veter.ne Admini.lr.tinn (rnter, I n+ AnRelen 25. ( lB/urni• 1) MIIRRnY nN(;I:VINF, M1), Pr.r. fr(rnr n/ ParhnlnR., l/nlar+ily of Wh. tnnain Medic.t Gha.l, M.diann, Wia. rnn•in i fR1 I1FR1('K W. PARNFt, 1R , M Il„ Pn 1) , Annclnrt rrn/rr+nr of MrJirinr and 1•hrrinlnRlrnl ( hrnJrrry, Inhna 11r.P1im I/ni.eraily School of Medicine, Pehimnre S, M.ryLnd CAM11U1 RFI 1 fl, M 1), f)/rrrrnr. pl. ririnn n/ ('nrArnlnRr, Phil.AelPhi. Oenera Ilnapit.l, Pbil.dclphl., Penn.yt. rrni. RI('IIARI) I PIN(i, M.I), Prnf.rv+r of Afr.lrrinr nnA ('hnirmnn. 17r/+nrrmrnl n/ AlrAtrinr, W.Yne St.le t/ni.ertily ( Id1cRe of MeJicine, Iklrr+il, Mkhl(lan IR111 () P(K K. MS. Pnl), Srnlnr ('nn. rr Rrrrn.. h l, rrnrid. I1rnllh Re- ar:u(h Inc , Rnawrll I'v1 hiriann, nurtaln, New York (.rr M.n+re) IAMI C 111(INNI~R. Prt I1, Prn/r+anr n/ The Me..urernenl of Ihe Functional Str lln of the Ilum.n He.rt hy Frequency S(reclrum Anaydi of iM Vihr.ti..nnl Fnet.y P.Ihnln(Ik -- Annlnmk Study of C.11uLr (h.n(te.In llumnn ilrnn(hi (C) The Rnle of llyptrpb.l• in Tiaare Re aPouae to Chronic 1).m.Re (C P) The FRec( of Nknline on ('.rdlae Irril+- hlltly in the Preaence of Reaerpine, and Ihe FRecl of NicMine on ('nronary Rlmd Flnw of t)nRl with ('urnnary Inaumciencr lP) The FBecl of SmnlinR on the ('oron.ry Rlnal Flnw and Certain Ph.ai of Myne.rdi.l Melnl.nliam in P.lienti whh ArIerioailaMic or Ilyperten.i.e l'.rdio•.xul.r I)i.taa ( P 1 Snhlie. in Ctlhd.r PhydolnRy of /le.rr Mu.cle MManremenl of Cmnnnry /llrwwl Flow hy Mt.ni of R.din.c/ivaed nlhumin Inve.IlRainn of Iht Rir.lo/irnl 1Rtr1I of ( iR:+retlc Smnkt I(' 1•1 I nryrnalic S1nJy of Mrlhylnlinn Rr.c (T IIr,.R.r•., ( ahrnrmn lnainne of Irrh nnlnRr. P:ra.r,lrn., ( ~..Irf.nnin lrnna In Plnnl I iaaur /t 111 V+ r.. I/7M (; r.h.r nr 11t1W1 RY, Pn il /'runiAr Rrr I.J.......... r. Ih..ni.rrr l+rl•nr NnN1. / nr.dm. til.rr / nllr~r. I/N: en.l f'ndrin -;rn.Ar (P/ Rrai~lnr. in !ir.rrln RrlriRh, Nnrlh ( nrohn. n SQ 59 rT ti-,

i fatANlFr: ANIr tNS-nT1/T1(/N M nRO71 K. Prt t), rrn/r,rnr, fnh,•r,rrnrr n/ rhlunlnRirof 11rRvnr, llniveraly of Minnraol Schnnl nf ruMic Ilrntth, Alinnrnry,li., Mmntar,U (nnw l'n•/rr.nr ,rnd ( hnlrrn,rn. 1)trarl~ mtm nf r.rch(`lnRy, 1 rhlsh llnirer ci/y, RrlMrhrm, rrnncylvani. ) I- M H(I1T, M 1), rr,./,,,nr nJ rnrhnlj nre. lJnivrrvey of G.u/hern C./ifnrni. Scl,nnl nf MtJ;r;ne, ( hrr/ rnlh.rl„Ritl, I rn AnRrlts ('nunly Iln.r;l.l, I ns nnrrlt+ 11, ('alifnrn;. RI( /IARf) 1/ nVr RRl/M, rn r), rrn. /rtrnr of ('hrmlvrr. MkhiR~n Stale l/nivrraily, IC.H I.nainR, MichiRnn WII I LAM 11. ('ARNCS. M f1, r.n/rtr,rr .•I rnrhnL,Rr. 1)nlvtr.;/y nf tHnb ( nl. Irre of MrJiclne. S.It 1.Ie ('11y, I/r.rh 1) ( 1 RI'( /II(1, Pnll, rrn/ra Ri- Lrrni,rrr, Inrdhnm I/nivtrdly, Nrw vnrl IR, N YY rnnw r,.,. /rn... nf Rbrrhr,nr•nv nnA Nunui.•n I/nirrnily n/ rurrlo Ricn. San 1n.rn rurrln R;rn) II.ANS 1( I ARKf~, 1hCr rr,•/„r•„ •.l Rinrhrrnrtr.y. I nlurnkl. I/nivrr.irv ( nllr~r of .rnrl Cnr.r,,,,. Nrw Ycul, N Y I.rr (:r.llar h..ll t tUl II/S 11 ('OMR(tl' /. , M It 1,,.,• tnr, ('nrAi,w.,urdnr Rrrnr.rh Inuu,•rr Vnirtrdly n/ (-.lifnrni. Mr~lrr .I Schr,nl, Snn frnntlarn )7, <nlifnrnrn I/1'AN M('ONN11RS, M 1), Arrr,inl, Ih.rrrr•r. I)rJwrlvnrnr oJ InFn,nrnrr Afr,Nrinr, St M.ry'. 1loari/nl, Mnai.nn {, W;acnntin rI111 Ir (Y)()rf R, M 1) ,('hir/, ,l Srrri,r, Vrlrnrn. ^Jnvniatralinn Ilna (,ir,1I, Rrnnc, Ntw Ynr1; ('Irni,nl ,•/ .(urRrrr, nlherl I ina/rin MrJiaal ( n11rRr, Hrnn. R/- 1)AWCrtN, rnll, rrnfrra.•, n/ Rnlnnr, Inlrnnhia l/nireraily, New Vn.), N V J, 1 I1WnRl/1 Itr)MIN/t M 11, A,r;,r,r.,r )'L,.r•..n...L•rr Ilm.rrarr, ~ ~ tJ 1'/(()J1fT TI7LF. piulnRia..1 fhar.rlrrial;r. Of Mrn n,l Ihrir [mnlinR lL,hrlt ((/'/ SInJy nf lr.re Mtlal SlnraRe rd Inh.n„n ary anJ I ivcr lnane by ~LrclnRra(.hir •n,I ( hrnlrtal Mr1I1nd, I(1 Pnlhr+lnric Analnnmic SIOJy nt (rllnlar ( hnn/rel in Ilum.rn Hrnnchi /( / pi,rynlhra;, of the ryridinr R;nR of Nicnline r.,Ihn/nR;c Anntnmic Cnn1y of ( rllulnr ( h;rnfra in 1lnman Ilrrmalri I(1 A SInJv nr Ira,ly ( hrmiral ( I,anrra in Ihe I unR. nf lumnr (1rarinr R.il. :m,l hOae I( r) 1•rn/r„I,l;r n,r;vir;r, of Ihr Whilt fllnrwl 1 rtt. nf Mrn .,n,l Ihr I 1)ral nf N'lurr rll A~ n.rl,r. n/ /,rr, ,„rrna r~~•4rr•,•n .,n,l rnhrr In/lnrn.r. 11 1 //v 111•,I „f CnnJ,nR trp.•r, 1n av Rr A Sthrdy nf /he ^Ileralir.na in /1„ Iluman Hranahi:J W.11 1)ccurrlnR wilh nrr;nR. ,.i1h rarlicnl..r tmrh.aia nn I l.ralit liaane ('h.nfrta and Aa.nciatrJ ( hanRr. In the Hrnnctrinl I umrn S;re A Clmly nl the I Rrc(s n( ('iRarNlr Smn1 iny un I evela nf C.-Wric At i,l, rerarn :,ml l/rnrrp,;n ((' rI A CrnJy nf Ihe I~Ilecl nf 1'tlrrcla of In h:,ccr, nn (ultures of lumnr and N•nrn:,l ( rll. Arumal Irin.l.line, r,f I umor I ia.ue fiom I iaaur (ullurr, 4n lnvrali,3l;nn nf Ihr MtLA.,di.m nf 1'yriJmr ( nmLnunJa in Ihr 1„Ln„n rt,,M IR,rra o/ lnhn,n Cn,n1r .nJ Nl,nl,nr ,~n Ihr ( rnrr ,/ Nrr.nu. Cyarrnr Id i G1IANTF.E AN11 INSTIT(rT10N )UIIN W. 1('KS11'IN, M I), Aidrlnnf I'rnJrtrnr n/ IMrrnnl M.J;,inr, (o11eRe nf Mnhaine, til.rt l/nrvrraily of lowa, tnwa ( ity, Inwn ItANS 1 FAI K. rn 1) . Atil,rnnr rrnlrr- t•rr n/ Rin, hrnun.., llniversity of Snnlhern ( ntifnrnia Schrvnl of MtJicine, I 0. AnRrle. )), ('rd;forni hnN/1 I FARNGWORIII, M D, Ifrnry K(1lfrrr rrn/rrrnr n/ IfrRrrnr nn,l lli rrrlrrr n/ Unnrrrilr llrnllh Srrrirr,. Ilarv»J llniver.ily, ('.mhriJRe 1R, Mu.aachuaetls /sre I/ealh anJ McArlhuw ) 1'RANK C Ff R(:IICON, 1% , M I) , ('hrrirnrnn, I,rrnrrtn,nl n/ rhnrnrnrnf nRr, /1lhany MtJical ('ollt[q Albany R, New YnrR RI1CS1'I 1. S t'ICtll'R. M 1), fAlrl A(r,l iral Ernnrinrr, Slate nl Maryland: /'r,• /rrrnr n/ I renl Afr,lirinr. I/niverHily uf MmylanJ MeJicnt Sahool, Rnllimore, Maryland H I I RFF1)1 AN111'R, M D., Dbrrrnr nl ('nnrrr Rrvnrrlr, M1. 7inn Ilocrilal, San Ft.nci.co I1, ('alifornia lsec frrnch) I RI t1/ R1('K A I RPN('I1, Rr.rnrrh Arr,nrrrrr, Mt 71111% 11n.pilal and McJical l'cnler, S,n I:,anciaco, Califnrni 1•ee FrrtJl.ndrt) /n( K fRl 11N1). M I), Intu.nln rhar rn,wrrlnR.. .Irrnrnnt ;n Afrdirlnr, Mrd knI 1 nllrRt nf VirRini., Richna,nd lo, VirRinia I'/11/JF./T TITr.F: Realrw,as of Ihe rtrirhrr.l Veinm in Man to the Inhavennus Adtninialralinn of Nkoline (r) Fnol Rlr.,d Ilow Rearonaes to Smoling in the Preaence of Ily(urliremia and I lyperleminn F..aminalion of CiRarelle Paper and <'!R.• ecOe Smoke ('ondensales ftx Aromalk Inlytyclic Ilydrocarbons (C) A Cnmrilalion of 1'luoresencc Srectra of Pnlytyc/ic Aromatic Ilydrocatlwns nJ ( loacly RelatcJ (-tvm)x+unds Whkh Arc of Inlereal in the SIUJr of Alr Pnllulanfs, and Ciprerte Smo'e In Re- lalion to I ung Cancer F(lology Ptraonalily and Smo11nR In Cnllefte (lr.d. u.Ir1: A, FFifltenYe.r Foltuw up Sludy ((') 1'ffects of Tnharco Smnlr I)pon Ihe Iunclinn at Iht ( mfiuv.uul.r Syattm in Aniu,nis anJ M.n P:dhalnRic Anatomic Slu,ly of (-rllyd.r ( h.nRes in Ilum:m 1lrnmhi W) 1'.trtrimenls on Ihe ('nrcinnRenic and Co tncinnRenic Atliun of lohncco rrol1 IK1s 1P1 ('atcinnRtnirily, (ocarcinnRrnicily and Anti carcinnRenicily n/ 1)ielary 1'clors in Relatlon to Pulmonary I umnr.. Pns slMe Interrrl.Nnnahip of Inhacco Rnaea anJ IHrlnry Inclur. ( hrrnicnl Sluditc nn PyriJine hacta IncIu,linR Nincin An aloRc (rwrelalinn of Mollileclmi..l rr..ctdrnev PttfrwmtJ nn the rtrirher.l (irtul. linn nl Narmal Individunl, in Rernm htnt an.l ISrecl rnailinnc anJ Allrr I.tttiae /lrfrae nnJ Altrr Ch.m and Aclu:r) Smn/inll A SInJy u/ Ihe IIltrta of ( IR:urtle Smn1 inR r•n Ihr 1'rri('llrlnl ( irculal;nn nf Indivialual. wida l~tlrriuulrruvia llhli /er:mv anJ olhrr rrriphtr:J Va.cul.u Ih.r..ara, lll;li,rnR hArdri /t, Imu nl I'rn trJurec 61

CRANtFF: AtVl1 IrySTITtrT'111W (:1 ()R(:F. O nl'Y, M D., Itirrrrnr. linnr.lhrrrrll ('mrrr Rrvnrrh InA. orol,v.. 1)rrnrlmrnr of .frnerry. lohm /lnplin. Iln.ri41, R.Ilimnrr, Maryl.n.l OFR 1 R I/hr Y C(y1 rS('l1Al t., Pw h. Arrrilnn/ rrr+frrrnr of Ri,~hrmlvey, hrpnrrn.rnl of rnrhnJnRy nnd AArurna hin/nRR Ihe RMlefeller Inlailule rnr Medic.l Rt'w.rch, New Ynrk 21, N Y. (Ke ( l.rl e ) A(-/ ARK (7RIF/ IN, Prt I), Ilend of S/nrhrminry nrl.nn,rrrnl. M f) Andrnnn Ilmpit.l and runux ln.tilutr. I/nF.ertily n( lr.al Medical ('enter, //nu.lon 21, lccn. MI)R I(/N IORIYCSMnN, Pu f) . M 1). Arrnrndr ('Lnirnl r.,+/rrrnr nf Alr•h r, ltnivrr.ily nf r..(r(nrnia MrJicnl <rrnler, I r.a ^nRrlra 71_ (~.bfnrni. ('ARI COR11//71T, Prn 1), M I) a Arr,viorr in rhy.iuL+r. nnA PAnrnrn rnL•Rr. 11nivrrrity of Pennlylvanln (7rndrule Schnnl nf MeJirine, Phit. Jrlrhin 1, rennavlv.ni. (nnw Irrnnrr in rA.rinR.Rr, l/nrvrrv/y nf I/nnr Kont) /1 n/IAA(7. M r)- r,,,/r,.,+r nl rhnr rn,rrnhrRy, Me.lical ( nllrpr nf VnRmi. Richmond IV, VirRini. /OSt rl/ It IIAI KFNC( 1fIFt , M 1) . /lirr.M., ('nr.li..prd..r.+nnrr f/nir I.n +~f ISi Irn.u /loapilr.l, rhil.rlrlrhi. 1/, Penn .ylvani• rrr~+~~rr+~a.... RI( /IAR)) rr.,/r.rr+r f'nlifnrnia I It of Mrd AV1'I , IN 1) ,,~rdv„nr Mr,l;r Inr I/nivrr.ity nf ic.l Cchrrr+l S.m I r,,n ci.cn (-alifnrni , • r.... , Ilf'RnFRr R IIAWTIIf1RNF M11 , . ('hnlr.non. Drrnrrmrnr nf .lrrrerr. (lnivrrdly o/ Prnn.l/vnni~ (:r~Jualr G InrJ nf Mr•6c irre, rhil.drlphi.+ 1 rennayl..ni• . r t ARK W 111^l11 MO rlh.rr,lnn YY I rry.rr.m.nr rl Il r e„ " ..r.~r. d.,. r r. I I- n,1 1 4n q/ . r. 1'11O)F(T lllLF: /-rn.rwahir. fnr .ClndyinA the ( uhure nf Ilnnun ( unR licwr anJ /he /flrcf. nr Known and Pnnihfe (.rcrnnRrnic A/trnh I/rrrn Snch lraaue rrolrolylic Aclivilir, of Ihe Wt+itr nLYrI Celi, nf IN..n .nd 11.r IRe(r nn Whilr R/ranl Irll Acfirilira nf (~..rcinnRrn., Nutritiun nJ (/rhrt (nflurn(r. The r'rfrcf of P..(rnarne to (-iRnrrlfe Smnle on Ihe Indnclinn nf ( anrer by ( hemical (nrnl.rwndt f(~ r) fhe 1 Rrcl of SrnnlinA nn (rrhur (:.vrlc I uncrr.rn. PhvmarnfnRir' Srndy nf Nicn/int an.t Rr I..reA nlt.tnid. /() rrrr,rarinn fnr rnr.lir,rnn nr a nr+.,l nn Ihr Ilr..lnric n.l.rr 1. rrf I r•h:+rr n.nd i/. Srn.+le (r) Mraarrrrmrnl of (rvnnary nlr.nd Ilnw ('.rJiac Wnr1 and(ardi.rc (lay/rn.rn,t (arhnhyJrilr Mrrnhnli.rn in Nnrma, fenaive Su(yref. Rrfnrr nnd Afler Inua vrnrnra Niculine and Afler SrnnlmR S/nnJ.nd (iRnteltel ((- r) A S/uAy nf the rflrclI nf Sm..lin1 and Ni(r+linr Adminiatrann on Symnmho adrrnaI 1-nnclinn anrl Iafly Arid MrUr hnharn Atlempf. /n Inducr rulmnnary Nrn pliarn- in r.(.rrimrnf.~t Anim:ila by 1.(vrvrrr nf Ihr 7r.vlrrn /Irnmhi:J SY. Irrn In Iul..u.n Crmrlr //1 rrr,r.n./iry .,ne Cnrr,lir+, in r,•nrrr r:r.,.l ir I'r (:RANTFF- AfVt) t'VSTIT(rTI/)rl PA(II INF? FIFt7FR, PNt), Rerr.rcA Arorlnrt /w ('yrnlnRy and Cyprthtm- Irrrv, S.n Franci.co Indilwe of Medi- cal Science+, San Prancnto IS, ('.li- fornia (+ee Richard.) Rl)Stf'1 ( 1. 11(11 MAN. M(),Prn(ttror ond llrnd. Itr/vrrlmrnr n/ rNhnfne1, I ovidan• Slafe Oniva.ily School of Medicine. New Urlcant t2, lordliana F. II(yMRURCFR, M f), Prtrldtnt. Rb- Reie•rch I •bot.fntiel, Inc.. C.m- hridRe, M.aucMnetM IrRRY IIARr /A( r1RS()N, M 1), In rrrrnr of flrrrrnphyu.+hrR., New Yr+r1 Vye and Far Infirmary, New Yrwl 1, N. Y. i ANf)RF.W A. KANf)(rTSCt1, PnD., ttn17 Srirnrirl, Rnacot R/aclann Me• mnri.l I.horato/Y, 9ar Ilarhor, Maine AN( J'1. KFYS, Pln 1) , Prn/rnor n/ rhq- inlneiral ll yRirnr nnd I)brrror, f nA. nrotrrry of rbrrirrl,reiul ll r/rirnr, (lni- verlity of Minnean/a Srhrn+l of Public Flealth, Minneapr+lit 4. Minntaol• 1()SFP/1 R KIRSNFR, M 1)., Prn/r.- rr.— r+f Mrri'i. inr, t/niveraity of ( hicaRn School of Medicinr, ('hicaRo, Illinni. IffNNI: .IIt P. KN(Ity1S(1N, MI), Ar ridnnr (hirt, lnAnrnlnry Srrrirr, Vcl- eran+ AJmini.lrafinn Iln.piul, Sealde, W.ahinRton, rrn/r.rnr of PnrlrnlrrRr, l)nivrr.tly n/ W.ahJnRlnn Medical ScMrn1, Sea/lk, WaahinRton AI.VIN 1 K(1SAK, ru f) . Atrnrinlr rrn• of ('hernrary, Wa.hinRlon Syu.re Co11rRr. Nrw \'m1 llnivervily, New Ynr1 Ih. N Y MARVIN K11S1lINI'R. M I), Prnhr+- rrf rorArrlnRr, New Ynr\ Univeraily ( o11rRe of Merh.rne. I)rrrrr.rr rrf rn rl„•l.•cv. Ilrllrvnr I/n.rit.J. New Ynrl la, N V IltttMAS (- I AIPf 1 Y, M 1t, Arnvinre •I I•,rrb..h.c. N.•rrh.r,rr.n (/nr.rrury Mrdrr..l Srhrnd, ( Li..~rr, llhnnia P/l(/)F,IT TITt.F A ComParaive Slndy of Farty Iliaotn1ti- cal and 1)NA ( hanRt. In Ihe hPiJermrl of T.o Slraini of Mice (t 37 Rl.clf and S.h. Wehder.) After 1)aity APPlict+/ionp of WLo1e ( i6areue SmcJt ('omknvte IAhrne and ( omhined with (-rmnn Oil) and the CarcinoRenf 7(/- MclhykA.danthrene and ),1 Rentpy. rene P•Ihnlnek - Anatomic Sludy of Cellular (-hanffe. In Iluman Bronchl (C) The InRuence of Inhatrn Smoling on Acute Myocardi•I Infarctinn Stucliea on ('arcinnReneail aml the Rio ....y nf ( atcinn(tenie Agrnl. 1 t' ) ( nmP.ralive Snn/iev r.f ( Rerla of Vari ocn Inhxcn Cmnlt ( undrn..lec on Sl<im of Mice A (bmPlriann of Flecltnte/innRlaphr al • Meant of FvalualinR the IiRec1 of VacrKnnalrklnr 1)ruR% llron ( ereAral and Retinal ('ircuFalinn Wilh e)Iher lechniQue7 fne'Ihia Otltrmin.linn W) To f)etermine to Whaf Flrnf tobacco T.r Mimkl Ihe Action of ( arcino- Renk Ilydlnt.uhonl in Ihe S1in and 1/lher'1ia.uel Characlerialk% of Men. ImludinR Smo1• inR, In Popnlalinna 1)iflerinR in Ihe InciJrnce of ( rNnn.ry Ilearl 1)i.e.ae (C rt lhe F/Iee1 of Tnhacco SmnlinR (Ilw.n naul C.vrie Seerttinnq in M.n PalhnlnRk-Analnmic Sturlr nf (~rtlul.r ( hanRti In Iluman Rrnnchi If / Ihe lanlalinn nnJ Irlrnliflratinn nf ( rr I.rin I nwer IluihnR ( nm(w+nrnf, of ( iR aretle Smult I(' 1 Palh.dnRic Anrlnmic StuJy .d ( rlhJ.r ( hanpea in ltum.rn nrunchi 1( / PnlhnlnRir Analnmw Slu.ly nf ( r/lyd.r 1/+:.n/ra rr. Ilnn+..n 1lrurnlrr Ir 1 bl

i (:ItnN7I F A(vrr IN1;71TIrTN/n P^111 S I nRSftN, rrt 1) • Prnf.rrnr of I'bn.n.nrn(n~r, Medical ('olleRe rd Virgini.. Ricbrnnnd 19. Viriffinis ( 1?( 1111: 1/ 1!('ll l l'NRf R( FR, Prt I) , Srnr,.. Rr,•l,.enr end ('ynwlrr.nrv, ( hit drrn's f ancer Reaearth hoandaion. nn,/nn, Maa,achu,Hls R(Inf'RTIt 1 tNNFI I, PrrF), Arrnriotr rrnJrrrnr of ( Annivr~. t)ni.rr,ity of Vermont, RurlinRtnn, Vermnnl /)AVIf) F MANN. Irr, Pnl), Aurrlntr rrn/rt.rr. of rhnrnrn.nlney. Temple tlni.er,ity Schnnl of rhnrmacy, Phrla Jclrhl. .o, rrnnayl..nf, t/IARI f'C C. McART IItIR, Pn F) , Prr rA,rln,ri't ro t1.r f/nivrnrry llrnlflr [rr rrrrt, Ilar.nrd (/nivrr,ity, ('nmMhlRe )/t, Ma,.achuarll. I,rr I .rn-nrrh .m/ 11r.1h / 1'It(I)FIT T1T1.F: I~ntvmarit lr.nafntmari.rrn .•/ Nltnlinr nnal Ktlaled ( nmpoun,t, 1 r) A ('nrrelare,l I li,lnlnl(ic.l, ('ytnloFienl and (ytnchetnic.l Stu.ly of Ihe Ira<hrn Ilrnnthii/ lree frnrn Micr I:i. prr,eal ro ( rR.rrr/e Smnke (I') lht O.i,Ialion of Nicntine hy (a,enu, OsyRrn: Methaniam, rrn,lucf, anJ Kinelica FRecl of Tn/..1cco Smnle nnd Tnhacco Revidur, (,n Melhyttholanlhrenr. InduceA Skin ('.rcinnRenr,n in Mice 1( ) S,.eiil and rrr,nn.l I)etrrminanh nf [ranlin1 Hrha.ror 1( 1'1 ( IfARI F.S H Mc( ANTS Prt O, Arr„ Ar,enit ( nnrent nf Soil, and Ahanrp/inn rrntr nf Schty.l of A/rie Lv the Inhatru I'I.rnr cutlure, Norrh (arnhna S41e (nllrlte, R.(eiRh, Norlh ( arnlina Kf:f 1 Y 1. McK/ l'. M 1), Ar,..rinrt rr,. Gudy nf I anR funcrion in Smnlrr, -J /r..nr of A(r,lu,nr Mrditil (~nllrRr of Sunlh ( volin., ( harle,lon, South (~.r oiina Nnn Smnlrr, (l r 1 FAMf S(7 M11 I/'R. M I) , rn f) , rrn the nr/uvinral 1"(Tects of Smn)inll 1!ndrr /rrc„r of PnrAinny on,l I'.nh,.L.R., end /)irrrlnr, Mrnr..l Ileallh Rr,enrth In,lilutc• Ilnirrr,iry .,f MithiR..n, Ann Arhnr, MithiRan III!(:11 MONIC(1MFRY, M1), Arr,ni urr rrn/nr.rr nf A(rfi,rnr, tlni.rtcily of renn,ylv.,nin MrJia.l Cah,wJ. Jrlrhii 4. Prnn,vlvania (:I OR(1F' 1' h1Ot+RF, rn f) , M Il . I+r r„r,.r Rn,wrll r.n1 Mrmnrijl In.ri rrnr, Itu/(..In 1, Nr. Yrn1 /,rr lhnl/ t111R1 1-Y 1 11 Mn) I 1 Y M 1) , r.,•Irr Rrrl•,rnr,•. y 1 nl•, .,i . rl /mvrr.ily uf C„urhern ( a1r!rnni.. C.hr.nl nf Mr,li . nr 1 m nnr,lr. I). r.J,fr.rnn Slrr„ InOurme of Ir.h1tco SmnkinR nn rhe III,MMI I hIW n/ Skin arol nf Mirarlr. nf I .rtrrnilie, in SympathrttnrmrrJ and Itn,ymp•rlhrclnn.iYtd Snhjrcf, (C) Inflnrnce of Nicotine (i v 1 .nd lo/acto Srn.rkinR on Ilhrxl I~Inw in Iluman C1in and Skelr/al Mu,tle An Invr,liri/ian nf the rhy,inln~i,ar f'f Irrl. nf tlirrtt lnhal:rtinn nf Iuh.cto %mn1r hy IIhntanry Anirnala ..n,l the CmAy n/ the 11inlnRiral Rr,l•.'n,t nf t.rhr.ralnrv Animala 1n ( nnnnuuu, In Rr.ri.•n nf I)irr Irrhatro 1'rr.lurl Mr rrur, t( I A Crr,dy of rt.r 11)r,tc nr Cn,,,linr nn Pirirnrn,.,ry tr,n,r,,.n It 1'/ I (:/tAWTI•.F. AN1r IrVV"TI!TI//rV Wit 11nM S MIrRRAY, Sc 1), Rrtrnrrh A...r.inv nnd A.Arunietrutinn f)irrrrnr, Rn,c..c H lnckann Memorial 1 ahnra• tnry, H.r Il:nh.n, Maine f)ONAII) M PA('F, Pttl), Prn/rrrnr of rhvtinlnry nnd f)irrctnr, fnrtilntr (nr frlhdor Rrrrnrth, ttniversi(y of Nehra,ks, I.inccdn, Nehr.,k• rl)WARI) W PFF IKAN, M h., A>'sn- tiotr Prn/rrtnr n/ rhn.mnrnfnPv nnd F. tprrimrnrnl 7 hrrnpwtlrt, Bn.Inn University Schocd of Medicine, Rrn/nn, M.n.chuselts C M POMFRA1, Pa1), rrn/rvnr of (-srnloll., tlniar,ity of le..s Mcdic.l Rr.nch, (7.l.eston, lesa r II R. PRi1TT-T11OMAS, M h., Prnfrs- rnr nJ rotbnlniry, Medicrl ('niklte of SmNh Carolina. ('h.rleslnn, Smrth C.r- otin. VICTOR RI(-IIARI)S, M.F)., Pro/rrsnr n/ .CurRrry, F..rrnNrv IFrnd, f)rport- mrnr of .ttnRrry, St.nfnrd (Iniversily Sthtrd of Medicine. San Ftancisco IS, ('.lifnrni. (see Ileirrr/ R II RIOFN)N, M 1) , Prn/erenr n/ rn fhnlr.Re nnd fhrrr n.r, 1 nhnrntnr. n/ F rprrrmrnrnl Ibrh.•fnRe. t/niveraily of 1 etas Medic.t Hranch, O.Iseslon, lena SYI)NI Y C R I T-1 f NP1 R0, Pn O., Pro- /r.rnr n/ H.nt.ri,dnR.R tlniver,ily of S,rathern (ahfnrnia, I cn Anltelrs 7, ( alifurni• RhN1AMIN A R11111N, Prrl), Anirtnnt rrnfrrr..r nl I'uhh, llrshh snd fYrvrnrirr A(rJr,lnr, Il.ylur (Iniver,ily ( rdltRe of MrAirinr, /lmra/nn, Itr., 1'It(/)F.IT T1TI.F. 7he Prrt/ncfion of renellc.Hy l'nnlrolled Anlm.ls and Itumcwa lot t/se in 1'trer• imenbl Rex.rch on Tnhacco in Ret.. tinn lo Fle.lth by (a) the Fer.nsion of Kno+'n Inbred Sh.cks .nd Srwrces of Tumtw SurNy: (b) the Production of Such Ilyhrids or tlelerntylorn Typn n Recame Necessny;.nd I c ) the Re~ I.linn of (his Material to Speciflc Pa- perirnenla/ Work.llhe I.horaorl (C) Fellnwahiln fne Tr.ining In lissue Cul. Iturt lechnp ocs Sludy of the F°Reels of 7oh.cco Smote ('nnaliluenlf on V.rinus Slrains of lis. stre ('ells Cultivated In Vltro A Shaly of Shtrc/ttre-AcN.Hy Rrl.don shlps AmonR I)ruls Which Af/ecl NicMineSensilive rhysiolnlic.l Mech- .wiams Fetlowahips fnr SHnlylng Ihe (-ulture of lluman Itune tissue and the 1'RecM of Known and Pmsihle ('.rcinofft•nk A(lents Upon Sr'ch 1 i,sue App/kHlnn of • Ner Rin A,s.r Tech. nipne In F..minatlon of (1R.rette SmoRe ('ondensates for Pnssible ('arcinoRen. (C P) Palhtslollie-An.lnenie Slydy of Cellul.r ('h.n/(es in l,lum.n RronchF (C ) A Ctsmis.r.Nl.e S/w1y nf the FRecls nf Whole .nd Fr.cHnnal Falr.cl, of ('ilh .rctle Smoke nd lho,e of Known (.rcinnRem on 1 11 '1 he ('rlo/c.q' and Nnclenr 1)NA ('onlenl td 1~'tdermis In V.riorn Strains of Mice .nd/nr ()) lht C~totogy .ml Nuclenr IINA Cnn /enl nf 1 ung .nd 1'rithelium n/ Ihe Rrnnthi.l lree of Mice nd llnmalrts (C) •I:Recls of Toh.cco Smoke ('nnden,are on 1he Rrcpirnlnrr Itnct .nd Other 1 iavres of Ihe 1)nc1 ( P/ 7he Rnctetial Ik(trndatl.xl of Nicotlne nd Rrl.led ('omrrnmd, 1 he (Ihjee li.e of the rrnjec( i, the 1:1rx idarfnn of the Inlermrdinry Metahcdi,rn o/ Nkm (ine Oeidnlinn (F') An 1'valonrinn of Ihe Phennmrnon nf lomn. Ornwlh Inhnmr.nrot ., an A,sny fnr ('arclnr.Rrn, mmonR the rolyryctit /lydnM'nrf•nn, •n,l Rrl.tr.l ('nmr.nmd. 6S

cIt1NT1.F: ANI/ INCT1l(/111/N WII I InM O. RUCSI 11_ M t)., rarhr,In. frrr rn chir/, M 1) Andcru,n Iln.rilst •nJ T umnr Inuihne, I/nlvtr.ily of tear Medic.l ('rnter, Ilou.lon 27, Tesss PA1/1. h S/1tTMAN, PNI'), Ardrranr rrn/rrtnr o/ Rr,rhrrn/ur~. (Inivcr.iry of Snulhern ( 1lifnrni. Sc hnol of Medkint, I os Angelr. 7. Cslifornl• A1 VIN R. S('IfM1f)T, PI/ 1) , n1rrernr of ('nunrrAnjr, i,dr. (lnlrerdly, Medford, M....chu.elr+ ICA_A(' S('/1r)I/R, t)I)t, Prr1), hSc, !•r.•lrrr..r n/ Irrv,dntr onJ Frnhry,.l..rr, and f)rnn. I)nivrr.rly of lllinni. / ol. Irefr of 1)rnri.rry, ( hicqn 12, Illinoi. MAI/RI( F S SF(7AI , M I), Clinfral rrnfrn.rr of A(r,lirrnr, luflt liniarfily Sthrw,l of Mrdicine, Rr.dnn, Ms.t•chu.rll.; I)nrrr„r !rr/a..rnvnr n! lnhalnlrnn lhnnpr, Rn.lr.n Cily I/naPil.l, Rminn, Ms,.ahu.rtl. (-AR1. (' Sf 1 T7FR, Prt 1) . RrrrnrrA frll,rw• In Phrrirol Anrhrnl..lor(r, Ilsr. rard Unirrrdly, ('smhridRr, M..vchu .ell. ('NARI PS p. S11PRWt7OD. M 1) , ArJrrnnl rrn/rlrnr of RnAlnlnRy. I/nl•rraty nf Rnchtatr Srhn.,f of Mcdi. cine •nd Uenliary, Rnthe.ler, New Ynrl I/^VII) I SIMON, M[), lnrrr~rrnr /n A(rAn rnr nnd frflnr in f'ardlnrnn rJnr Rrcr.nrr h, Ilnivtr.ily nf ('incinnnll ( nl~ Irse nf Mrdicine .nd ('.rdise 1 sMrrs~ Inry, ( ineinnnli (ienersl Ifn,pil.l, I in tinn.li 29. UMo 1'flllJt:(T Tffl.F: rnlhnlngic An.rnmic Sludy nf (rllul.r ( hsnRri in Ilum.n Ilronchi (C) The 1'nrymslic Mrchsni.m frx the h.rk Fisu/ion of (Y), by tnhaccn ((' r) Some As/,ects of Amino Acid Me1aM,liam in !oh•eeo I esver Study of Aldtude. Tnrsrd, s. Well .r F./rnl, Tyre snd Itivory of, lnhscco Smnking in • YounR Cn11cRe Pnrut•. linn. S/udy of Sr.n,e nf Ihe Rrlalinnt fhir. of Smnling snJ Nnn.mmking to Fnmilr Hidnry, T~.e of SeconJ.ry Schnn1lnR, Acsdemc Intcrr.r., Acs- drmie Arhlevement, and Socisl Rels linmhi(n ('h.rscreri.lits tlidnlr.Rlc ('h.nRr. In Ihe ()r.l, rh.ryn arnt .nJ Ns..l I i..uel of 1./,rrimrntnl Anima. Suhjec/tJ 1. Tnl...co Sn.oke . (( r) /1)ectq of ClRarerle SrnnkinR on 1 ung t-unc/iun in Nnrmel Suhjrcri nnd P.. tirnl. Wilh ('trl.in RttPiranry 11i.rnae ( nn.6tinn. (t, r) Rrlilion,hip nf ( iRsrellt SmnlinR to ( hrnnic 1Oh./ruU,a) Pulrnnnsry 1'm rhyarms Mrurhn/nRy snJ SmolinR in ('nlleRe (:rnJnarr. A I i(tern Yr.r Inllnv, lIr SluJy In.e.liRslinn Into Ihe N.thrr.l /li.trxy nf ('srcinamm of Ihr I unR Wirh rnrlir 03, Reftrente In the RsJioRrsrlrie Arlr.r- snce nf Srn:h Prr.cr..ra, the ferlrral Msnifrat.tion of (nnter nn ( htd X Rsy PholoRr.rh. .nd 1he Tshulslrnn nf the Rtlslir,nchir, of Smokint Ifshitr •nJ (tccnPs/ion Wilh Ihe InciJtnce of I r/nR ( .ncer (C r ) lhe I-RrtrI of Chr-inR Toh.tco on Ihr l.nlrn..atutsr Syatrm nf M.n ((' P) Ihr 1(Irrl. nf Pipe SmolinR •mt (iRsr Smr.)inR on the (srdinrnacul.r Cyarrm nf M..n I M S()NNI:Rf)RN, Pu 1) , t)IUfn ( fhrrIrnl nnd I.rrn~linR Ithr Crrrh.nn rrdrhr.l trrrlrr I'r..frrrnr nl 7m.6.rr. I',r..r..rr,rum Ira f.a (~.rcinrqrnn.rr Iroh.n. I/ni.rr.rrY, Ilhwmdn~lr.n, InJi 1 (:RANTF'.F. AN11 tNeTITItTI(ttv P1111)F.(T TITI.F, SAM SOROP, P/t [), Rrrrarch Ar.arlarr, ('hemk•1 •nd Phy.k•1 Slrnlit. of Ihe )he Inailute for ('sncer Re.earch and Ti.are Proltin. Inrolve./ in Chemlc.l 1•nkensn /loapit•I Rt.rsrch In.dtule, C•rcinoKne.i. (C- P) Philadelphia 11, Penn.ylr.ni• FRFI)FRICK 1. STnRP., PH 1')., P.o/rs• Ptlrrtrnent•1 SluJies of Cancer 111I11rIng rnr of Norrirlnn, Il.rr•rd Schod of • Ne.r Technique to Sce If V•rkws Public Ile•Ith, Rtnton 15, M•vchu• T•r: F.wfr•cled Frorn Tbb.cco• May ,t•1/s Incite the Formation of Lung Tumorr (C) MARION R. SU/ 7RFROFR, M D., Pro. Inve+tlRstlen of the PRects of Tobacco frr.nr and Chalrman, 17eporrmrnf n/ on the Ilum•n V•xul•r Syslem, R.sed 1lnmarnlnRy anA S)phitnloRr. New on the Fact that ('erl.in Toh•cco Ff- Ynrk Univerdty Rellevue Mtdk•1 ('en- fecb are Uue to Allergk SuuePlihility ler, New York 16, New York of SPteUk tndi.Mun1. Rather Ih.n lo Ohli,atnrily Tn.k Prnducts in Tobacco Smo1e, and Ih•1 P•tknls with (kclu- sive Vs.eul•r (N.es.e. Re.pomt I)ifler• • entlf th•n Hesllhy Smokers (P) ('AROIINF RFI)F11 THOMAS, MI), Tlx SIRn1Bc•nct nf DiRerrnt Indlvldosl Arrr.rlnrr rrn/rrrnr of AlrAlrlnr. Iohnm P•Itern% of Circld.lory Re.ry.n.e 1o Ilnrkln. Itnirerait) School of Medi- (-ig.retle SmnlinR (P) cine, R.llimrwe S, Maryland Studies of Genetic 1)Illtrence+ Rttwetn TISSIIP. Cl/l TURF ASSOCIATION (PrrrlArnr, 1)r. M•rl•rrt R. Murr•y, Acrnrinrr lrnftrrnr n/ Anatnmr, Co. tumhi• llnirersity Co/leRe of Phrel, cisns snd Sur~eon., New York, N.Y.) IANFT TR/1VF1.1, M D., .Innciare Pro- /rcrnr of ('l/nirnf PhermacnlnRy, Cor- nell llnirerai/y Medical ('otlege, New York 21, New Yor1 F 1). WARNFR, M 1), Prnfrrinr of Pa rhnl.re . Sl.te l/nlverdtT of Iowa ('ol- trlte nF Medicine, low. ('Ily, 10.•• RI(ltARt) 1. WF( IISI FR. M[), l~hnl. rnl Phy.i.JnRiU, Mnnte6r.re Iloaritsl Inailule nf Rr.e.rrh, PilHhurRh I1, rrnna)lv•ni• R11tCF11 W WFI I I'R, M 1), rnrhnlo eru. Mrrnorinl 11n.pil.l nl ( l,raltr . 1'nun1Y. Wra ( hr.4r, Pro (v.,nu Arr..r inrr, rrr.lr.rr•r, nf I'nrn.I Il.rhnrmann Mr.lh nl f o11rRr, 1'hAs./rl phie ), rrnn.yLenis Smnkers s.d Nnn.mo\ers (P), StuJrrs of P.reholo(tkd t)iRerence+ Relwern Smolers •ml Nonsnx,lers •, Shown by CornP•risnn of FiRure 1)r.winlts To Mal.f In Fetahll.hmtnt of Summer Tr.ining Coune In 1 i.are ('nlture T'echnlyuti sf l/nlreraly nf Colorado MtJk.l Schod, tknrer, ('nlnr•Jn ((') Pflectq of Nkollne In the Rabbit .hh F.Perimenl•I ('oronsry Atherr.aclermi. PsthnloRk•Anslomk SIuJy nf ('elhd•r ('hsnRe. In Ilumsn RroncM ((') Correlation of Rronchi.l FPllhtli•I ('hnnRet oilh Comparable ChanRe. In (Ither (h11.n.- A Pslhnlnpic-An.lornic Sludy Fflect of ClRarelle Smoking on Cerehrsl MtlshnN.m, Rlnnd Flnw, Cerebral Rh,nJ p/l, Arteri.l rnl.e 1'rr.aroe Crovr., 1lltclroc'.rdinp.m., snJ I:Iecnoenceph.InRrsm. ((') Pslhnlnl(kAnslnmlc Shwly of ('tllulsr ( hanRti in llum•n Rromhl A 41ctItJ, I~.tended nd 1)rladed Ctud) nl I lum.n Rrnnchin) Muc r,.s 67 0{1

(:ItiN'I t F. AN11 tNfl I t l l-I I//rV SIN/I/N /1 WINIIIR, rn f) , Rrrr.rr.h /•rrrJr •rr ../ r J....... rr t/„i.rr,rl, nr It{I.hnnr• Rr.rarcf• In.rirnrr, Nrnrn,.n, (N/.hnrn• IIIIANI I7 WI N71 I rn /) . r.nlr.r..r n/ rhn nl••Rr CrhrKd nl 1•h~nn.ry. Ilniver~ilyrnf Kan~ , I...rrnrr, K.n u. I Rf'//1RIt K f' Wl1ISKIN. M 1) _(' M, l7,rrrrnr, hrrrunn n/ llrnlrh nnA rrr nnnlrJ, FprnlrMnnn, I h, AIr ( tnlrr nf Ne.v inRl.nr1, In, , nn. lnn 16, Kla, ..c hwrll, 1 II,WIN WI)/1/l, Alln, rnr•rr••- qlr,)rrrnr Mr•fua I rdl"r ol ~u~u.r.• (irrvRr. Ifr/1N r W Y A I1, MII, r..•lrrr~•r .•/ rnrhnL•Rv SI I ...... Iln .rr~rr~ C•hr.d ol MrJninr. SI 1nnr. Ir. h/~.~nurr t•11(1)F/l ltftt•: A Ouolir.,live inJ Ouanlit.rIivt Shrdy of Ihr lndrviJn:J PrdVrhrnnl (~nnlrnl nf ( iR..rrltr Inhaccn anJ if Ihe Smnle nnJ 'lar,' RrwllinR hnm (iRerrlle SruolinR, nnJ Alao St.rJy of Ihr Pale of 1 he,r ( ornrnunJ, in the Anim.I Rr,r6alory Sy,len. W P) ihe hrtermin.linn of Ihr ( hrr.nie I rtecl, of [)ralfy AJminiurrcJ Nicnlinr on $rrum ( holr,ternl .nJ rhn,phntiriJ,; the I Itcl.ncarJinRrarhic Rr.Mrn,e in FrRr.nr.vine; anJ /hr Va,cular ralhol nRy nf ( hnle.lerol fed R.hhie. 1C - PI PJot Sludy if /he Smr.linR Ilahil, if ARr, ( rotrr Mrn.hrH Ihr I /lrcl nf /•rnlnnrr•I /nhrdarnrn nf I oh u ur I n.rdr and nf 1'rr.InnRtd At. /n/•ocrn nn 1luvnce frnm thr Il" of Ihz t•rrirheril V.anrler Rr,l•.r- to Arnle In/nlnrinn nr Inhnro Smnlr in Mnn /(' 1'1 An Invriti~..rinn Inrn /f,r Nalorr rJ Ihr 1'rprrnrnl.rry I tiir•n rn ( rnlrilnf•ul- I ny•6y.rma I, Y A 8 0 a 13 0 ® 0 F7

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