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Abstracts uE llcpxorts Fach recipient of a grant-in-aid from The Council for 'Iuhaccn Re- scarch - U.S A. is responsible for the initial presenlatiort or publication of the results of his research at scicntific meetings or in appropriate scientific jcwrnals. Ftdlnwing are al.stracts, approved by the authors, of reports on new eRperimental research acknowkd6ing support from The Council that have appeared in scicnlific Kwrnals since publrcation o( the 1966-67 Report of the Scientific (hrcctcx. '1 he name of Ihe grantee is in italics. These abstracts have bcen grouped under thesc headings: I. Psycho- Physiological Studies, 11. Carcinogenesis Studics, I11 ('ardiuvascular Sys- tem. IV. Respirattxr System, V. Neurophysitdngy, VI. Studies at the Cellular I.cvel, VII ('cll and Insuc Culture, ViII. fpidemioloRy, IX Pharma-:ology and P.rycho Pharmacohrgy, X. Metabolic Studies, X1. Chemistry an-F Bio- chemistry. XII. Other Sludies, and X1I1. Reviews. 1. I'rycho-PhyaiofrrRicrn[ StudiPa ALTCRATIONS IN TIIE 8I:IIAVIURAL ANO 111(X'IIF: .MI('A(. EFFECTS UF Ii1.EC1R()CONV(11.SIVN SII(K-K WITI1 NIC(YIINE Flectroconvulsive shnck (F.('S) adnunmtcrrd tu esperimental animals riRftt after condrtioned-response training priKlu.cs a rNrr,grade arnncsic effect. In eapcrimcnts wherc mnc wrrc IacUCrtcrl with nrtraunc sellatc, this amnesic response to shrxk was srfnrhrantty hhalcd by thc JruR Ihc attenuation of the relrogfade amncsn w.r% pirtrtutarly apl.arYnt whcn drug treatment was given 45 to 60 minutes fauir Irr trarnarg Ihc high incRlcnce of conditioned response retention in drug trcatcd nirce was paralleled by  reversal of the predicted cRcct of L'CS upon brain senNonin levcls. While the rclationship between ECS-induced clevatitm in whole brain scrotonin kvel and F.('S induced retrograde amnesia is n<>t necessarily causal, the niccNinc-induccd reversal in hcwh areas of the customary F('S enects sug- gests a postibk corollary of the drug-irxluced facilitation of memory con- solidation. E.-simon, W. F.. Steinberg, M. L. and Golod, M. 1. Ptychonomir Srirnrt 12 ( 3): 107-1 OR, 196R. nth.r Rrnntnr: National Institulcs cr( I Icalth. Front the Ihpartmenl of PIychr>tr~gy, Oucens ('ollcge of the ('ity (Inivcrsity of New Ytxk, I lushing, N. Y. 1AS1l; IIIR[SIIO1.1)S IN 'IWINS ANI) SIItLINGS l aste threshrdds for hydrrtifiluric acid, quinine, aud 6-n propyldrioura- cil (1'Rt)1') wcrc dctcrmincd in pairs rrf munu7yg.rtrt' tM7.) twins, Jvygr+tic (1)7.) Iwins, and siblings (SIB). The numbers of pairs involved wcre 75 MZ, 71/ I)/., and 7R Slli, for the latter two compounds; 26, 45, and 45, respcctively, for dre acid. Significant differences in intrapair valiance werc found ( I) between the MZ and the same-sex I)Z pairs in thresholds for bittcr-tasting PRUP, and (2) between the male MZ pairs and the male UZ or male SIB pairs for hydrochloric acid. The difference in intrapair thres- hrrld variance was not significant for bitter-lasting quinine. Intrapair differ- ences observed in the ML twins indicate that nongenetic (actors also influ- ence taste thresholds. lhugs, smoking, and the menstrual cycle are among the environmental factors t:ut may aRecl taste thresholds. Other obscrva- titxu showed that, with all three contpounds, repc a.ted taste Icsts on the sanre subjects yielded high numbers of results similar within a single thresh- old range. Also, in 31)R subjects, ccxrclatiorts between thresholds (or the different substances were positive and significant. Kapfort, A. R., Fisher, R., Karras, A., (3rifftn, F., Powcll, W., Marstcrs, R. W. and (ilanville, (:. V. Acra (:enrrirae Afrdiruc rr CcmeffolrrRiae 16(3):229-244, 1967. Ot'h.r grantor: National Institutes of Ilcalth. From the 1)epartntent of Genetics, Clevcland Psychiatric lnstitutc, l'Icvr land. • I 1'FIYSIOIACiICAL ANU PATIIOL(Xi1CAL CORRlil-A I IiS 01: E)II'FERENCES IN TASTE ACUITY l he effects of various parameters (genetics, dietary prcfercnces. age, sea, smoking, biological acutty, personality, mcnslruation, dutxlcnal ulcers, and gastric ulcers) upon taste acuity are surveyed in this relwrt. When nxinu7ygutic (M/.) twins, OizygtNic twins (1)Z), and mxMwin sibling (SIR) pairs were tcstcd (or intrapair differences of taste thresholds, it was seen that Ihe intrapair differences in the MZ pairs were significantly Icss than in either the UZ or SiFI pairs. In other studies, sensitive tasters of quinine and 6-n-pnrpylthinuracil (PROP) reF+orted relatively large numlrcrs rd fo«Kl dislikcs and a pre(crence for mdd-tasting foaxls, comparcd tu inscnsitivc tastcrs. -Ihe xnsilive tasten included a relatively hiEJr pruprxtinn ul nrm- smukerc, compared to the insensitive taslcrs, who includcd a relatively high proportion of heavy smokers. Taste threshold was ncN found to hc relatrd to age or sex when smoking habits were cspcrimcnlally cuntrrrlled, but heavy smokers were observed to manifest decrcased taste scnsitivily with increascd age. 1'hascs of the menstrual cycle were srmtctimcs a.srK•ialcd with significant changes in taste thresholds. Apparently, hiRh taste sensitivity for Ixrth quinine nd /'ROI' may be assrKialcd with hiRh gcncrol systcmic rr- at'tivity, and vicc vcrsa 'I hcre also a'~pcars to tic a INnsd.lc aa.rriati~rn with pcrsun;rlily di/lercnces. Imlividual JJkrences in tasle acuily pattcrua, rr latcd tu Frrth genetic and nrxrgenetic variables, have also 1K•en assrK iatcd with significant dillcrcnccs in peptic ulcer pathrdr-Ry. UurKlcnal ydtcr 11.1 ticnts, as a grr.up, were signiftcarntly more acnsilive lu thc taatr ul 1'I(/ lt', but not rd yuininc rx hydnx•hloric acid, thrn either gastric ulccr paticnts of nonpaticnt c-ntrols. IR 19

Kal+lnn, A. R. Prngrrrt in llumnn Rrhaviur (;cncrirl, F)ahimure: luhns llupkins Press. 1969. pp 11- 66. (hh.r Rrnnror.: State of Ohin, 1)epartment o( Mental Ilygicnc and Cra- rcclion; and the Nalir,nal Inslitulcs of Ilcallh. Frnm the I.atxxatury of Mcdical Genctics, Cleveland Psychiatric Instilute, C]eveland '1111? !)IS(-nNTINIIATION OF CIGARETTE SMOKING: A MUI-7IPI.E !)ISC'RIMINANT ANAI.YSIS Multiple discriminant analysis, a technique which permits analysis r>( categorical dependent variablcs, is described in this paper. 'Ihe slaled technique was applied to an analysis of the relationship between a smt,king discontinuatit,n lypt,logy (smnkers, smokcn who have been unable ta quil, and quillers) and 11 psychological ard socinlogical facttxs theoretically rclaled In srnnking behavior. 7he II indcpendcnl variahlcs studied were: (I) average daily cigarette consumption; (2) mention of specific present health ailment; (1) smr,king behavior of wife; (4) aRe; (5) educatNM; (6) age when started smoking regularly; (7) chance orienlaliun score; (R) e+ttraver- ti(.n scfqe; (9) neurr,licism scrtte; (Itl) consumption of hcer, wine, or whiskey; and (11) Ilr,rn's attitutk tr,w,rd smoking scale. Using Ihcsc vari- ahlcs, a ma>timurn (IkeIIINMN) (llnllN,n (nt eich sml,king group was cr,m- puted in nrdcr to stuJy gpr,up crMllifurihnns in the prcdiclr,r space lhe results of this statistical sludy are inturf.,,ratcd in Ille hdlnwing related abstract. Straits, H ('. (Karr, F7du,l Srudirt nnd lJrurr in Smr,Arnx lrrhnrr.,r, '1 ucsrm I he l)nivcrsity of Ari- zona Press, 1967. pp 79-R1. RIiS(1ME UI-' '11I1i ('lII('AGO S7lIUY 01: SMOKIN(: Ill?11AVIOR In order to examine the pnx•ess of giving up cigarette smnking, per- sonal inlcrviews were conducted with G,ur groups of males: nnnsmr kcrs, es-srm,kers, current smakers who tried hul were unable lu quit SmckinR, and current smokers whu had never made a serious attempt tu stup sm„k- inR. In additirm, brief interviews were cnntlucled Willi the current asstf-iates (clnscst relalive-- usually Ihe wifc, clnscsl friend at wurk, chnest friend away frum wtNk, and family doctor) r,f the resprmtlcnts in nrdcr to eaanline interfxrsrmal cnvinmments An alleny,t to r;tl,p s,nr,king was aarwiatcd Willi the prescrxe uf physical ailnlcnls (cspcti:dly Ihtnc ca-ily cr,nnc(tcd Willi snloking), heavier tobacco cnnsumlHir,n, less sul,lnulive intcrpersr,nal environments (I,arlicularly if the wife was a nnn.rm,ker ur an e><-srn,-kcl), a relatively unfavr,rahle altitude /l,ward srn„kinR, and a nr,n fatalistic r,ut- 1rw,k r,n life Sur ressful quitlers trndcd h, f.c r,l,lrr anrl lu hnvc the alw,ve- mrnti,mrrt char:,,trrialics (wilh Il,e er,el,ti,al n( I:,lalisrn) Irr a Frcalcr , tti n/ Ih.,n IL••~i im.,l•Ir 1„ %1,-1, Slrails, 11 C (Knlt. I:Idru). .Studn•t mul lsrucr in SrrurkinR Rclravirrr, Tucson: l he llnivcrsity of Ali- rrma 1'ress, 190, I,p 7)-7g. Fn,m Ihe lkparllncnt of Suciology, University of ('hicagr,, ('hicaRu. TASIIi, OIX)R, ANf) TAC"T'1l-G UISCRIMINA'1:ON llliFORI? AN!) AVf I:R SMOKING !)iRetential sensitivity was measured before and after sntuking a ciPa- retlc by seven snlokcrs, using sia mmsnNrkers as controls. Stimuli cunsi.tcd of the tactcs of slcruse, sodium chloride, citric acid, ca0einc, and quinine hydnKhloride; Ihe txftm of vanillin and 2-hulanonc; and Ihe viscrnily Pro- duccd by a carragcenan gum. No significant "just noticeable dillerenccl' were ohscrved between smukers and mm-sn>okers, nor before versus after smoking. 'I-herefore. the data supcxled neither Inng-term nor sharl-term in- fluences of cigarette smoking. Practice eRects were noted among the control gruup, as mrxe correct resprrnses were obtained on the second than on the first set of sulutions in most of the test stimuli. I'nnxhr.rn, R. M., TraMre, 1. M. and flarylkcrPikiclna. N. 1'crcrydiun and P.rychrrplrytic.r 2(11):529-512, 1967. Frcxn Ihe University of C'alifnrnia, 1)avis. 1'fll?('t O1' ('I(iARf:7-fl: SMOKING ON PAR(YI'IU SI'.('RIi71ON l he eRccts uprm unilateral parotid secretion 44 indcpcndcnt visual, taclilc, nlechanical, nlfacttxy, arKl irrilational slimuli asslKialcd Willi srn„k- ing were mcasurcd in a small graup tA smukcn nnd ntrosrn„kcrs I llc I,acc effect r,f srnr,kiog per se was eslahli.hed se'taralcly using a);n,up of SII su/ukcrs. In all gruups, smoking Irrr rr slgnihcantly increased pan,(id secretion (1 5 to 2.1115 tinrcs greater than resting Icvcls) Silnple 1•rclhlc, dfactury, and vi.ual (watching another smoke) stimulalit,n I,r,oluced nn significant difJcrcnces. The act of drawin~ through an unlit ciparcllc and of inechanical hlrKking of the rn,se, causing muulh hrcathing, resultcd in siRnilicant incrcascs in secretion Snloking a ciRarcllc while wcaring I;npl•Irs which cumpklcly climinalcd visiun pnwluccd considcnl ancl hil•hly sl)~ruli- canl dccrcascs in sc.rcliun crnnparcd t„ smr,king withr,ul visu:rl „hslrur- lir,n Since rcalin/ kvcls alsr+ wcre Inwcr wht•n visirwn w:rs I1LK kcrl, it Is snfp-slyd 111.11 Intrr(t•rcnle Willi Incnt.ll l,.ncCnlydUwn m lllt(nUmn rc~ullr,l in inlnhdinn 44 «, rcliun which is undrr aultwrumic t uuur,I Ilarylkt,t l'ikiclna, N, I'nnrtborn, R. A( and Shannr,n, I 1.. ArtlnVfJ o/ I!nvin rrrn~nlnl llrvdllr a7(S) 71) 71R, 1968 Frnnt Ihc I)c1+:rrlmcn/ nl Vrw,d Scirncc and 'Icthnolnry, 11„i,cr"ly ~d ('aliltxnia, I)avis. 21

E1SITEII.NI:SS OF I'(iFR RAl1NGS (>1: t'NRSONAI.IIY IN FI)UC'A'1 tONAL RIiS1:AR('ll 1 he rclatitxnhip between personality nd academic success, thnugh recr+gnired as im~+cxtant, is not well urxkrttaxl. 1)a1a repuled here (ctm- IriMrlcd hy 1,42R students from colleEe, high scMr)l, and nursing schtMd) indicate that rccr ratings of personality can be hclpful in clarifying this clusive relationship. E/sing this metlwJ, rafers e>tamined each of 42 hipdar r rsrrnalily Irails nd selected the five members of their pxr gn,up nun/ c the left hand {xde (positive nominatitxu) and the five most like its of+posite on the righl (negative). The theoretical rationale umkrlying this rating method and tlre mctlxulalogical probkms encountered in its use are disrusscd in delail Results are presented conccrning the reliability and factor analytic structure of peer data nMained in all three fxq,ulalions studied, and cnnrcrninR the prediclive vatidity of pecr and mm '~cer data obtained in one sample of 349 college students It was concluJeJ that Ihis rating system is a valid and useful one, and, particularly, that the peer variables hehrnRing Iu the factor called here "slrenRth of character" are impxxtant rxminlrllective eorrelates of academic tuceess. Smirh, G. Af. f:durorivna/ and I'tvr hrr6oRiro/ Mraturrmrnr 27(4).967-9R4, 1967. Othrr Rrnnrorr: Il S Public Ileallh Scrvice and Spaulding Polter ('har- itable 1 rusls. From the Ikpartnrent c,f Anesthesia, Ilarvard Mcdical Schoul, and Ihston Elniversity, Ekntun 11. (:arrinrrgcrer'si. titrulira Animo/ Experiment. 111JPA11C: CAR('IN(xIENFSIS IN ('11A/('h/Sc MI('E? ANl) ('b/Se RAIS hY ISONI('UIINIC ACII) Ill'URAIIUI: ANt) I IYURA7.ING Sl11.P11A1 l? I rrr appro>tirnalclr ten ycars, rcccarch in this latwralury (in iscnict,- linie atid itydraride ('NII) has IKxn Jircctrd luward elardying whcther INII and its dcrivatives (1) act carcin„rrnicany in lung t'antrr reso+lanl mice and in rats, and (2) induce tunu,rs in muuu and tat Iissucs rrthcr than those of 11re lung. lhe rresent palxr sununarires this actunwlalcd wtnk and puts tpecial enq.hasis ufx,n tlata perlaininR to Ihe numlx•r, inci- dence, nd induction time t,f turnqrrs i4 thc liver in c.pcrimental rnitr anJ rats On Ihe basis nf the accumulaled resulls, it ii cmncluJed that a njaliK- nanl /umur nray result from the use tA INII lhe validity r,f Ihis t'unclu- sio,n is attcstcJ to by the fact that hydraiinc, which has bcen shuwn to tK tartinr,Kcmc, is the prrrxipal mclatw.lttc ol INII Sevcri, 1.. and Niom rfi.,ri, ('. I.-urmJrr/ drr lYnnunal ('onter Institute 41:331-349, 1'76R. Ilthrr Rrnnt.rr: Anna Fuller Fund. From the 1)ivision of ('ancer Research, University of Perugia, Italy. E/t:IRASIR(Il'IURA 1)1?1 'IUMORI POI.MONARI INIK)7-1I ('UN IURAY.INA SU(.FAIO IN 'IU1'1 IIALtI/c/C'b/Se 1 he ultrastructure of pulnN,nary tumors induced in 16 (iAt.ll/c/('h/Sc mice with an ayucous solution of hydrarine tulphale was studicd hy light and clectrun nricrrscnhy. tlrxkr the light micnscupe Gre pulmtrnary turutus werc c1•rssificd ns srrlKl arwl papillary atknomas slwwing st+nrc dcgrce of anald:nia. t)ndrr the ckctrun microscrpe, a chnc similarity was (uund Ix Iwccn Ihe atknumalous tells and normal alveolar ccl(s suggcslrng au alveolar tttiFjn of such Lulmorury tumors. The eresense u( Ihrcc lylKS u/ viral particlcs, namcly: rn,racisternal 4A> parlrcles, elongalcd or tuhular parliclcs siluated in the cislcrnae of endoplasrnic rcticulum, and inunalurc C particlcs, is rcfxulcd here. Bucciarclli, E., Rrnncifiuri, C. and Rosi, F. l,ov../nnr. Pat. l'rru)tia 2R(I):41-55, 1968. I)tlh.r grantor: Anna Fuller Fund. From the 1)ivision of C'anccr Research, l)niversity of Pcrugia. Ilaly. 1?SISl1 NLA E)1 lIN I~ATTOR1: ORMONI('O NIa I.A ('AN('I:R(X:I:NFSI I'()I.MUNARF . DA II)RA"1.INA llx sp.ntancous incidence of lung tumors is low in intact virgin and pmadretomircd ('11A/C'b/Se mice of both sexes. IliKh daily duscs u/ hydrarine sulphate (h s ) increased the incidence as (ulhrws'~ intact virl;ins: malcs 7I.%., fcnialcs 91/%.; gttnadeclomired: malcs 72%, fcmalcs RII^,- Il.s. given in smallcr dtncs is nwre active in fcnule than in uudc virgin r»ice. In grrnadectr,mired mice, the lung lum(x inciJencc is lower than in the treated intacl virgins (a11Kit hiRJrcr than in unlrecdcJ cunlrt.ls), and Ihc dillcrcncc Ix•twccn tlrc sexes practically disappcars. I)aily du.cs rd t) 56 mF of It s. gave R7'"• lung tunaxs in inlact (cmale virRins and N/;t. in inlact virgin malcs; (12R mg daily gave 56'iS •rrnd Ih"'o reslrcclivcly, and 1/ 14 mt; duily 41/%„ and 7 %. 'fhc lung lumur incidcnce in grmtadcclr,nmcd mitc was 2R^ln in fcm:dcs nd 21% in malcs with 56 mK daily, 24''1~ and 1 I'"• reslK•tlivcly witlr 112R rnK Jaily and R^,4, and I1"L- with II I•1 rng d.uly Ithcsc results sul-yc~t that a Ih4unu,nal fatl4u may Ir inv4,lvc.l in I ulnum.uy carcinr,grncsis fry h s in ('DA/('b/Sc mite liionr,151(ori, ('. Lav. Anat. Pat 1'cruRia 29(I) 29-41, 1969. (hhir grantor: Anna 1-ullcr Fund From the l)ivisirro of ('ancer Rcsearch, llniversily of PeruFia, Italy. 23 22

A('('Ii1.fiRAIION OF GROWlll OF ('IIF?MI('A1.1-Y 1NUtIC'I?1) TUMORS BY USE OF '1 RANSPI.AN fA l IUN 'I I;C-I iNI(' Previous studies of subcutaneous tumor formation following irijection of SIK/ r-g of )-1,9,10-dihenypyrenc (henrcr(rs1) pcnlaphene) have shovn that, in general, 50% lurrxrr inciderKe is reached in 11 ttr I S weeks, and I(X)% tumor incidence is seen after 25 weeks In the present study, subcutaneous injection sites /rnnt 40 donors were pr><.led and transplanted into 10 recipi- ents. When carcirnogen had been kft in nfu in the primary host I'or five weeks or longer, tumors arox from transferred injectwm siles in ttie sec- ondary hosts with great speed which was significantly incresud over the rate of tumor development observed after primary carcinogen inirction. The 50% level occurred as early as nine weeks and the 1(K)% Irrel was reached from eight to 12 weeks after the original carcinogen InCctMrn, or about threc to seven weeks after transplantation at the injectwon site. Thus, this technique shortened the time required /cw carcinogen Iesting. Results of this esperiment suggest that five weeks of contact with caninogen suffice to cause malignant transformation of mouse fibroblasts in vrvrp. 1lnmAur)irr, F. and Treger, A. C'ancrr Rrrearch 27:1203-121), 1967. Orhrr Rr.wf.r.r U. S. Public Ilealth Scrvice, Virginia and 1). K. Ludwig Foundation From the BioRcscarch Institute. (-ambridge, Mass. EXPIiRIMFiNTAL S1l1DIFiS ON lI1F. INFIIBIl1UN OF CARCIN(XiENFSIS BY ('1(iARETl1' SMl)K13 ('UNDfiNSA'fES AND C'ARC1N(X;F?N-RELAT EI) SUBS I ANCI:S A series of esPerirnents was undertaken to study inhibition of tumor growth in mice by crgarelle-snwkc condensate. llrese experiments included: (I) quantitative determination o( spontaneous lung adencxnas in female A/He mice receiving intravenoaa cigarelte-smoke condensate injections; (2) aystematic st.dy o( the lung idenoma incidence in untreated A/Ifel mice; (3) determination of lung adenoma formation in mice receiving i.v. injcctions of TcAon particks in Rin6er's solulion, Ringcr's solution lone, or denkotini:cd ksbacco tar in the same vehicle; (4) olnerva(ion of the eRecl of i.v. (njections d condensate on induced subcutaneous sarcomas, and (S) on transplanted sarea.nas. In addilirm,  series n/ espcriments was run with the derivatives o( benro(rslllpcnlaphene to determine the carci- nngenicity of these poteaNial inhibitors. Resulls indicated that the i v injec- tion (if tobacco-smoke condensate arrested thes~+~mtancrnua lung uknornas of A/Ilel mice at an early stage and inhibited thcir suhscVucnt pr+wth. Tlre growth rate of induced and Iransf.lanted urcr+mas was dnwed sigaifi- eantly by the condensate. The tested inhihiaNs reduced the number of lung tumors and reduced overall earci nic putency. 1 hw, evidence is ~e- sented here that ciRarelle-smoke corx nsale contains subdances that reduce lumrK growth under certain circunntances llnmhurgrr, F.,'1'rcger. A. and Roger. P. T'aM•nrd A I rrs llorm/ul ('iRorr(fr, National Cancer Institute Monugraph No. 28. pp 259-270, 196R. OIb.r Rrnnror.: National Cancer Institute. 1)ivision of Research Facilitics and Resources; Virginia nd 1). K. Ludwig Foundation. From the Iliu-Rcscarch Institute. Cambridge. Mass. MUDIFIfRS OF CARCINOGENESIS Sludies are presented here on two experimental systems for the testing of carcinogens in mice; namcly, subcutaneous injection and site inspection, and intravenous injection and study of lung tissue. In the first esperimental system, the eflccl of sia Jiflerent vehicles upon Ihe carcinugcnicity of S(10 r of bcnzo(rsl)penlaphene (DBP) in (*S7B1/61 mice was esamincd. I)i0er- encea in the rate of Iumtx dcvelop rnent were slriking, with average lalency pcrirx)s ranging from 16 weeks svhen peanut oil was used as the vehicle lo 62 weeks when 11,0 was the carrier. Concomitant studies showed that nxidative derivatives of UBP administered to the test mice at critical times reduced the rate of growth of DBP-induced tumors. In the i.v. sludies, lung adenonu incidence was measured in DBP-Irealed and control mice of ten variant strains. Both strain nd age differences were appreciable in these tests. llere, also, derivatives of UBP tuch as diacetuay 1)111' and 1)11P-quincxte acted to inhibit the growth of spontaneous and induced lumorc Since complex mixtures such as tobacco snkrkc, air prrllutants, and fossil fuels contain tumor initialofl, promoters, and inhihiturs, it is imprutant for this to be kept in mind when such mistures are being tested for carcino- Renic potency. llurnhurgrr. F. and Tregcr. A. 1'rrrKrr+t irt F.'rrnimentul Turnor Rrsrarch, Bascl/Ncw York: Kargcr, 1969, vol. 11, pp R6-99. O(her Rrnntor.: U. S. Public lleal(h Scrvite. Virginia and I). K. I.udwig fuundatiun. From the Bio-Rescarch Institute. ('ambridgc, Mass. A('C'FiLERAl7:U CARCIN(X&N 11?STIN(i In expcrimcnts with male ('5781/6) micc aud m:rlc Syri:rn Iraurdcrs, transplantation of combined carcinoKcn injcclion sitcs frrmt (unr 'aimary hrnts into une secrmdary host siKnfic:urlly acceler;rted lumnr Krrrwtlr in thc secondary recipient. 'shis aeceleration of malignanl Rruwth rr-curred re F:udlcss ut Ihc tirc rd the initial drnc td catcinoRcn. 1fi.trdnr~i.nl, ryUo Irrrical and cytlKhemical studies of Ihe carcinuFt•n injecur,n srlr•s tn ruue shrrwcd nn inrtial.lassical frncifn-l>taly rcacliwrn Irdl4rwinl; vilhhIc inlc4 lnm While this rcaclion rcKresscd in cunurrls, in thc 1)HI' inlcrtrd ;ronnals atypical RNA Io:rJcd fiF,rrrhl:uls incrcascd in numl+crs a.ounJ tFhc inlrr umo sitc and aaswucJ tlic Iraltcrn typical id /ihnrsarcrmoa In thc inilial inllammalory rc-'ptmsc was Icss rnarked. Ilonvcvcr- thc alyllis,J Iihiu 24 25

hlasts seen here occurred in small clumps Ihrrrughnul the suhcutanclrus fat as well as through Ihc periphery of Ihe injection silcs, 7he results rr( trtcsc euperimcnts suRgcst that the RNA loaded fihrnhlasl represents a prcnt rlig- nant cell form, which, kf1 in thc original host, tkvclrrps into fihrrrsarc irna slnwly, and when transferred into a fresh htnt, more rapidly expresses its malignant behavior. flomburRrr. F. and Baker, 1. R. PrrrRrrtr in Ezprnmrrrral Tumor Research, Baacl/Ncw York: Karger, 1)69, vol. 11. pp 354-394. Other grentorrr (1. S. Public Health Servlce, Virginia and I). K. I.wlwig Foundation. From the Bio-Research lnstitute, Cambridee, Mass. TIIF. Nfl:t) OF EXPFRIMENTAL INIULATION STl)UIIiS IN ANIMAIS FOR 1111: PROBLEM UF 'lllli INI L(IIiN('1: 01: CIGARIiI-1E: SMOKE ON THE IND(1CTION OF LUNG CAN('I:R This report stresses the great need for experimental model sys,cros which permit JupAication of the human hahit of cigarette snNrking as clrrselr as ptnsihle in lalxsratory animals. Tht autfwws review their own work witfi inhalation techniques and express a desire to stimulate concentrated ellurts of and ct>flabtxatiun between scicnlisls from varitxws disciplines nf chcmistry, biology, pathdngy and expcrimental cancer research in developing and pursuing large scale inhalatitx+ wtxk with fresh cigarette snsoke. Su;h a rNnt and concentrated pmgram would pcrmit direct analyses o( the hiu- hogical cRetls trf many sushcctcd faclnrs, intlutling air pirllulants, rcy+ira- ttxy diseascs, rathalinn antl rrlhcrs as wcll as tig.uctle smokr It wuulJ oku permit asses}rnenl and exclusion t>t thute faclurs ulxcurinR an c.act cvalua- liun between particular factors airrne or in comhinatinn and Ihe qKcur- tcncc of pathtsingical Itcntitrns, and thus it would he nf great valuc frrr clarification of causes and pathogenesis of lung cancer in man. l.euchtenhrrRrr, C. and l.euchtenbcrger, R. Zrirte-h(i/l fur Priivrntiv-Mrdizin 13:122-129, 196R. Other grantnr: ('iba-Basle, Switzerland. From the Swiss Institute for Experimental C'anccr Rcsearch, l-ausanne. RI:PROl)t1C't'IV1: FFFF.('fIVFNFSS IN CROSSI;S BETWI;FiN FIVE INBREI) S7 RAINS OF MI('E In Ihc course of ongoing genetic studics of carcinngencsis in nrice, detailed records were ke~ on ccrtain uf Ihc rcp rt~luclive uclivitics t-l micc protluced by 14 crrnxs fxlween Ilx /ive inbretl strains ('311/llrl, ('57111./ 1+1, MA/Myl, ('31IcB/Fel, and A/I lc) I lie data presented here rcprc- srnlinp tNdy Ihe first F, litlers prtnluccd hy Ihe (ruracs 14 the five parcnral sUains incluJc, for each of tlrc 14 tn,sscs, di.lrnbuti4rn of liltcrs hy silc uf liltcr; age tr( rnrdhcr at hirlh (r( firsl litter; tnlal in/ant nwrlality; R, of "lusl" Intcrs; raliu of inlatl tu tkplctrJ litlrrs; sizc (d inlad and Jchlctcd litlcrs; ^,i. (if t)c/dctrd litters in each size categttty, and sc>t ratios of intacl and depleted hllrrs. 7 his material is presented for Ihc frnelit of trthcr in- vcsligators inlerestcd in analyzing the genetics and physitduRy rd mice with di/terenl viral and constitutional faclors in various conrbinatiuns. l.ittle, C. C. and Murray, W. S. Journal of thr NatNpfal Cancer InJfltntr 42(2):219-225, 1969. Other Rrnntnr: National Cancer Institute. From Ihc lackson Laboralory, Bar Narbor, Me. C'AN('FiR(Kif:N1:.Sl FPAT7CA NF.1 TOPI CDA/(b/Se F N1:1 RAl-11 Cb/Se 1)A Il)RAZINA SUl-FATO 7 he spontancous incidence of tumors of the liver in ('BA micc is 11% in malcs and 4% in femaks. Administration ot ist.niazid (INII) tlid mlt ahcr the numhcr of liver tumors, but hydrazinc sul'thate (IIS) raiccd their incidence It. 6296 in males and 71 % in females. 'l lte avcragc induc- litxs tinrc was 6R and 61 weeks, respeclively, after start trf Irealmcnl. Ilisloingicalty these tumors were hepatocarcintxnas. In ('b rats, liver lunwrs were olrscrved in fuur out uf 13 IIS-Ircalcd rals and in une uf 49 INII- trealed animals. Spontanetws liver tumtxs are never seen in ('It rats It is emphasized that a malignani tumor could originate (rum tlrc use uf INI1 I Scvrri, l.. and Diancifiori, C. F'pmnrfnRia 13(2):199-20R, 1967. Other Rrnnfor: Anna Fuller Fund. hrom the 1)ivisiun of C'anccr Rtsearch, University of 1'crugia, Italy. TIIMORIGUNESI POI.MONARF, ('ON O SI:NZA INFA/(II 1)A I-I.11OR(X'ARUON, l)A ISONIA7.IhG (1 IURA'LINA SU1.1-A1U IN RA I 1( ()SIIORNE-MI:NIN:L/Sc (hhornc-Mcntkl/Se rats of both sexcs, with and without Ilwtrticarhlrn- induccd nrulliplc pulmonary inlarcls, were irxrculalcd intralxrit0nc:tlly with high doscs of isuniazid (INII) and hydrazine sulphalc (IIS). I.unF Iumrus dcveltMxd in Iwo male rats treated with INII ant) in fuur 11% injcclcd tals Pretreatment wilh Ouuracarlxm did nu/ enhance the action rtf INII and 11% as could hc clearly seen by the fact 1ha1, u( the sitt tuntors, three tlcvcLqTd in Ilutatkarhtwr Ircoled rals and the other three drvclulx•d in rnls withmut OuunK•athtm induccd pultntutary inf:ut/s. IlistoluKically, Iwtr rsf Ihc lumms were early atknonurs. Iwu paprnary cntcinrunas, unc ana1rla~tir rart rn"mu artd tme undi/lerrntiated cpitkrmoiJ cnrcirHrina Ncithcr /N11 nrrr IIS was t'alrahlc uf inAucing squarnuus mclahlasia even in hrunthi oud hrrrnrhnrth enclorud wilhin pr.nunlarct uirndie areas In adArliun, Ihrt•r r:r/s rnrK ul:rled with IN11 dcvch.twA tlrar ccll t'rrtimmrns rd thr knlmy Ilrts kr'lnry t'arcinuma is a lunrsrr which ducs not t><tur slwntancuu.ly in t6c ulncro,cd strain of rats. 26 27

Ribacthi, R. and Giraldo. G. (Scvcri, l.ut in) (.av. Anar. /'or. PcruRia 28(I) 5-19, 1969. From the 1)ivision of Cancer Research, University uf Perugia, Italy. ('AN('E ' RS INUtI('1a) IN UIfFERFNI' SPIi('11:5 llY ('UN f INIIO(IS , RAUTATION Although s/xcics and strains o/ animals differ in their tcnt:cncy to develop tumtws srt,nlaneously, radialion cacinuRcnesis Icnds to ovcrride cspccted diHercnces in susceptib8ity. A y source t>( continutros radialiun (cobalt (H/ wires) implanted in young adult rodents and capablc of inducing canccrs of the types expected in this sptcies, will also prtnluce cancers which rarely tkvelt,p spontaneously 1 Etese are epitkrmtad carcinonta td tfte esopha8us and lung and, also, tntct>Renk sarcoma F.Lcrirnests with micc, rals, harrntcrs, Ruinea I+iBs, anti dwarf rabl.its show Uut the ral appears susceptible to lung cancer; Ihe mouse and hamster slightly r.uscepli- ble to tnteu8cnic sarcoma There appear to be Oplimal drne and dtne-rale ranges frx carcinogcnesis, but thcsc may be obscured by biological varia- lions. f4'arren. S anti (iatcs, O. Archiver n/ Envirnnmrnrot llralrh 17(S) 697-7(14, 1969. nOther Rrnnrtrr.r U. S Public Ilcalth Srrvice and Atomic Fnerfy ('um- mission From the I alMnalowy of 1'ithM--Fy, IL~~.irJ ( an,rr ('iunmic~i ~n, anrt thc (•anccr Rcscarch Instttutc, Ncw I rtl•LjnJ Ikdtunta Ilrslntul, (:linir•ol Inrr•sfiRafirrna RIiSII)IIAL CIIROMOSOMAL A13fiRRAlIONS IN FI:MALE CAN('ER PAltENTS AI--fF.R IRRAh1AIlON 11Il:RAPY After thcrapcutic irradiation c><{~ostrre, residual chromtnomal defccls were repeatedly seen in the culturct) I)mplttxylcs of 14 patients studied. Radiation ellccls were assessed by analysis (r( cells frur» serial, s~ntcd pcrinceral Mmnl cultures obtained durinK arKl allcr Ihcrary. 'Ihe rnilial and nttnt imnxdiale eRecls were quantilalivc, anti affcclcd the rrcyurncy of eclls with chrtNntntrrne conrplements devialinR frunt Ihe nrxnral cunytle- mcnl of 46. llris increase in the numbcr o( ancuPhrid ccllt rose tu a Plitcau thrrinR therapy Althtw8h by rnte year after the crrtttlusisrn id Ihrrapy Ihe numl.cr of cclls with Ilte normal trrnqrlcmcnl u1 46 chrnmu.rrmcs LcKart a shrw rise to Prctrcalnxnl Icvcls, Pt•rsisling slructural alxrrathi-ns ul the thrinnrnrnncs wcre sccn long after the tcrminalirm uf raclialion Ihcrapy. Arnmrr.rr, A. I'.- Plotz, 1? J. and Slcin, A. A. Ft tlrcrinrnrtnf and Molec,dar I'adroLrRy 7(1):58-91, 1967. 11rh.r Rrnnror: Antcrican Cancer Society. From the fkpartmenl of (Nntetrics and Gynecology and the Institutc uf Espcrinrcntal Pathology nd 'inxicolo8y, The Albany Medical ('ullcge (>t Union Univcrsily, Albany. N. Y. t.A RI('I:R('A Ula.l.'ASI)ESlO NE:1 T(IMURI MA1.1(;NI PRIMI7IVI 1)1?L POLMONE Forlr-cirJrt lung cancers, collected over the Ihree-year pcriotl 19067. were analyred itx asbcsha bodies. Oihcr p+ssible causal facturs suth as smokinR and the prult.n(Ccd adrninistralinn uf drugs used in hrlrcrculusis therapy were vlso crmsitkrcd. Of the 4111 cases sludicd, 23 were srra at nccrtqny anti the other 25 at surgery. Ilis/olo8ically these lumors wete as fulluws: anaplaslk (69%), squamtws (22%), adentkarcinutna (4^G0 and nrirtcd (4%) in thc necrepsy malerial; anaplastic (2R7o), squamous (5670), adt•nncarcinoma (4%) and mixed (12%) in the surgical ntalcrial Under Ihe given experimental conditions, no asbcslos bodies were found in Ihcst IunRs. As rcl;:uds Ihe tNher facltxs studicd, o( the 23 necrtq.sy ca.cs, 15 had been srntrkcrt, scven had been treated over a prMracled PcritKf with drugs uscd in Iuberculrrsis dterapy, arwl four were ExMh smukcrs and had had anli- luhcrcuhnis Irealment. Analysis of this material showcd that clinical diag- nosis anti diaRntnis at necropsy are still dillicult. 'Ihesc ubst•rvalirrns serve tn limit tbe value of statistics on Ihe incidence of lung carcinrNna. 1'eactK•k, 1'. R, Riam-ifirrri, C. and Bucciarclti, li. l.uv. Anar. I'ar. l'rruRia 28( I):29-)9, 1968. Frum Ihe llnivcrsily of Peru6ia. Italy. 1?XAMINA'f1ON OP Ll/NO SMIiARS I-OR ASI1F.SlOS BO1)IIiS IN 109 ('UNSIi('(IIIVr: Nti('ROPSIfS IN PI:Rl1GIA Smears prepared frtxn the necropskd lungs of 109 Lerstms dying of various causcs were examined mkrosttq.kally fur asbcsltn twulics. 1•ivc ol the pcrst„u nccrupsicd were Ieenagcrs, and the aKcs nf the ulher aubjrcls rangcd /rnm 23 lu 9(1 years. Ashcsttrs Mxlics were found in rmly unc caae, an R1-ycar-old man in whom two ashesttn btKlies were dclrt'tcd All hul 11 rrf Ilrc Pt•rsons ncerulnicd had bcen residcnls rd Pcrugia. a nmn irnduslri:J city, ra rif nciyIiIwirinR small tnwns and villaRrt in tlnttai:r 'Ihr I4iw in tir(rttcc ( I%) nrdrd in this rural area stands in auiktnF cr.mr;rtl In thr 211'X% tur nnnc incirknt'c rcpKlctl hom nuny other Parts td Ihc wrald widr ulhrrwisc cunyratatrlc hospilal IN'pnlati,Nrs and lalwualtery I.rtihtrc. . 1't•acrKk, P R, Rr'nnrfirra, ('. an4I ISu.ciatclli, I: liur,yrrnn Inu.nrd rr/ ('unr er 5' 15 5 15 R, (969. 1--rum the Ilnivcrsily of I'erugia. Ita1y. 29 29

RI:fROSPI:CIIVIi SIiAR('II FOR ASRIiSIOS 11OUII:S IN Nli(•RUI'SII;S ANI) /f1Ul'S1f;S ON ('ASL'S OF PRIMARY MALIGNAN f I)ISEASI? O1~ 1 I IE 1.(JNG A total of 53 primary malignant Iumors of the lunR, diagnosed be- tween 1965 and 1067, were hislolo6ically confirmed. All the lumors, with Ihe exception u( five observed in scalene node biopsy, were re examined for possible assru'iation with asbestos bodies. No ashestos bodies were found in any case Smoking and antituberculosis drugs were also invcs- IiRated as Pxnsihle causative factors, but it was not possihle to establish a definile asstxiatitxt with the (umors. (H the 53 lumtns, 39 werc in srnokcrs nd 14 in MM- or es-snwrkers. Anlituhercutosis drugs haJ been used in seven cases in which there was also active pulmonary tuhcrcuhnis assuci- a/ed with the malignant disease. Peacock, P. R., Rinncifirrrl, C. and Elucciarclli, E. F.nrupeon lrnunal n/ ('untrr 5:147-133, 1069. From the Universily of Peru6ia. Italy. l1N T RFATFb Ilt.AhUFR CAN('FR: 31 AUfnPSY CASES Tumrrr histology and patterns of spread were studied in these 31 un- treated blatkkr cancer cases. Nu metaslascs were found in I I cast•s, cipht patients had mclattases in regional nrnlcs nnly, eiPJrt patients had mctas- lascs in regional mKlcs and elsewhere. aud four patients had nrctattascs at sites other than regional r>,Klcs lhc frryucncy uf mctaslacis in this serics, as in scrics of hcaleJ cascs, is relatrJ Iu depth r+( lumur penetrati++n in Ihr bladder wall anJ to bl+w+J vcsscl mv,rsnrn by lumr+r IlnttduKically. Iransi- tional cell carcinonia was sccn in IR ta.cs, cffrJcrnund carcin+rma in II) cases, and fxw+rly drfferenli:rtcJ adcn+K art inr+ma in Ihrec. ') he histologic grade nr type of lumrrr was nu/ appircntly related tu either the dcKrec of estensitm or Ihc distribution of nrctaslascs. Frirdrfl, G. ll and M('auley, R L. The Journal of IlrrrlrrRy IIN):293-296, 19hR. nth.r Rrnnror.: U. S. Public Ilealth Scrvice and Atomic Energy ('um- mitsion. From Ihe 1 alwualory of Palholr+Ry, PrmJville Ilr+spilal, Wallxrlc, Mast., and Ihe Cancer Research Institute, New England lkaconess Ilospilal, buslun. lII1? VAS('III.AR SUPPLY lO MFIASI-A'll(' '1(1MURS O1 IIIIi 1.UN(7 I'ulmonary arlerial anJ venous patlcrns in 44 mclntlalic pulnu+n:uy nc+qd:tamt wcre invetthRated hy meana r+f vinyl ncclalc cr+rrrni+m sfwt nnrn%, r+n ntf•tvnq ral+hit' r.nminatirrnt, an+l mi+rmrnfjvltr:y+hii late stnrhrs I hc vinyl att•Iare s/xtirncns rcvcalcJ ccntral nvaaul:+r arras with Ix.+lu.c fa•riphrr:J l+ntm"rn:rrv :rrtrrial anJ vcnr+n. :nlti+rrnrtiun Micrr+stry+ic stuJrca Ir+4 .I. I J. h.. ll. ++iJ,n„ +d la,lh Lnlrm,n.nv .rrtrri.rl :mJ vt'nuuc vrl+l+ly in all spccimcns. •Ilte histologic tlemonstralion of pulmonary arleri+dc- vcnulc shunlinp within Ihe ntulules supporls this previously /w+dulatcd mctfianism for hyl+rt.cmia in hematoRcntNrs spread mrlasl:dic pulmunary nctrplasms. Signrficanlly, the denwmstratitns o( arterial presence in all mctaslatic pulnronary neuplasms studied lends supput to Ihe cuncepl of pulmrmary arterial infusion themothcrapy fur metasutic prdrnonary Jisca.c. hronchial artery infusion is, however. the rtwte of preference (ur brun- chuRcnic carcinonta. Millrr. R. lL and Rosenbaum, A. S. .Slrrlrrry, (:ynrrnlr+Xy ti Obsrrrrirs 12S(5):II)09-1012, 1967. ntlrrr Rrnnt.rr: (I. S. Public Ileallh Service. Frr„n tlte I)anicl H•auRh Institute of Anatnmy, 1cRerson Medical ('ollvKc, Philadelphia. STtll)II~S IN "1111? lillO1.(x;Y ANI) PREiV[iNflON OF Itt.Al)1)I R CARCINOMA I:xcrction of 3-IIOA and 3-110K before and after thc aJrninislration ttf a 2 gns Iryptophan loading dose was evaluated in notmal individuals, Paticnls with a history rr/ bladder lumor, arnf smokers. "1 his samt• cvalua- tion was rc ateJ after nral administration tr( cnuuph ascorhit: atiJ Iu secure siFnif~ant ascorbalc kvels in Ihc urine. Smokcrs were included in this s1uJ~ because of previously publishcd ubservalirrns sup);t•ain); a rcla- lirrnship bctwecn cigarette smoking and bladder carcint„n:r. Ntr dillcrenccs were seen in the urinary excretion of 3-11OA and 3-I1OK arurnrK the Ihrec gruul.s. I kterminatic.n of cinnaharinic acid (cumprwnJ I V) was fuunJ to he significantly higher in the urine spccimens fronr p:rticnts with a history of bladder luonrr, dun in the urine from norrual nr+n-smnkcn Ascurhic at'iJ adutinislra(iors uniforndy prevented consfxrund 1 V fuunatbun When urinary chemiluminescence (('1.) was measured. Ille mcan rnunl appcarcd cun.iJcrahly higher in urine specimcns from palicnla with a history of bladder tumors and smukers than in urinc sl+ccimcns (rr m mrrnmal non-smrrkcrs. Oral administration of ascorbic acid suf+f+resscs (l in all instances. Sr lrlrXrl, l. 11., 1'if+kin, (7. F., Mishimura, R. and I)nkc• (: A. 7lunurrrinnt u( rbr Amrrirun AtJrKioliun .+/ (:r.rnu-I/rrrrnrv .Irn/rr+nr 60.14-21, 19hR. Othrr Rrnntur: Nalional ('ancer Inslilule. I-'rom Ihe Ik•I+arlmcnl r+f SurRcry. Scttion of (1rulrrFy, 1ul:rnr tloivrrsily Stlurd of McJrtrnr, New Orkans. I h11'1ASIAIIZ/.n/IONI{ 1'O1.MONARI? Ii A1.1.(1IRAI'IANIAIIII 1IA (SAR('OMI MIIKINI I)A MI: III.(YIt.ANIRI•NI-) In a study uf nrclattalic Rrowdu JcvclrqrinK in thr lun/;. Ihrr c mrrhyl chr+lanlhrcnc-inJu+cd munnr sarcr'mas wcrc Ir:msld:rulcJ rn .r•nrs aml thc IKhaviur +rf the Ir:ur.l+lants was oh.crvrJ I:xannnalinn fur lunl nr+t.r.l:r.ct 31

in Ihc rrcipiemt of the ttrain specific lumnr iarfraftt gave t'nntlanlly ne0alive results, even in the cates whcre the Rralt h:rd hccn rcnuwcJ to prolong the life of the mr.use Asf,ecific suhlincs uf thcsc lum,qs Rave risc In lung mclastates only in the rccipicnts from which Ihe graft had been surKically rcmrtvcd 'Ihe highest irx:idcnce of lung mclastaat (3A 5"7,1) was in the recipients rif atrecific lumnr isngrafls from which the Iunux had hccn surKically renroved during the third or fourth weck. f ussitde faclrrrs allowing the IunNrr cclls spread by the primry growth In survwe and mulliply, in spite rr( the immuniralinn of the recipient induced by the antigemcily of the tumor, are discussed. MaltVeff, N., (Srvrri, l..) l av- ,/nal. f'ar. 1'rrnRia 2R: t 29-144, 19hR. Fnrm Ihe 1)ivision of ('ancer Rcsearch, University of 1 crugia, Italy 111. (:nrrtiornscttlnr Svafem llrerf A ('OMPARAIIVI: S/IIUY OF NIIR(X7LY('FRIN ANI) PRO1'RAN( )LOI. A newly dcviud strain gauge cathctcr was utcd to measure the action of suhlinguwl nitroglyccrin and mlravr•rnrut prrqa.rnulul on slwnlening of right venlrit'ular fihcrs in paticntt wrlh and withrrul coronary arlcry dis- ease. Ilcmrxlynamic pararnclcrs and changcs in Ihe nsidatirtn rcductirrn prNenlial of hearl muscle were also drtcrmincrl Nitroglycerin dccrcascd ahortening and vchxily of .htrrlcning nf vcnlricular lihcts in n-mm:d anti artcriusclcrolic suhjects Alw tfcctcated in LtNh Rruu~s wcre Icft vcntricular cnd-diaslolic and syslemic pressure, Iensinn-limc indca, stroke inJcs, peri- rheral resistance nd left venlricular minute work, whereas heart rate was mcreaccd Intravenrws pntpratNdol Icd lu a fall in vehtcily of sh<xlcning uf myrxardial fibers, heart ralc, stroke imkx and left ventricular minute work. Ilowever, there was an increase in lensiun-timc index antl peripheral re- sislarxe with no change in syslcmic pressure. Lcfl vcnlricular cnd-diastrrlic pressure rose significantly in artcrfusclcnNic paticnls.'Ihe tnycxarJial nxida- tirm-reduclion potential increased after nitroglycerin whereas it fcll after prtrprandrd in nnrmal and artcrirnclcnrlic patients. Rrrhin, I' , Cnwan, ('„ Puri, P., (ianguly, S, Ik Flrryric, 1: , Martincr, M, Stock, T and 1lrnR, R. 1. ('irr nlanrrn )6(2):175-1 R6, 1967. (Itfar Rrnntnr.r 11 S 1 uhlic Ilcalth ticrvice, Mithir.an Ilcarl Aartiatinn, Aorcric:rn Mcdical AsstKiatirrn I Jur•rriim auJ Hcu•arch Vuund:rti-rn, anJ Ik•Irriil (icncr.d (lntpilal Rcscarnh ('rrrptrratinn Frurn Ilic Ik•pirlmrnt of Mcditinc, Waync Statc Ilnivcrtity SchrK l nf Mcdi- t ine. I ktrr,il 1? IIIT(T 01: NI(Y)IIN1: ON CONIRA("III.f1Y (1U "1111? INIA(-I III ARf A slrain RauFc calheter assembly was uscd tu study thc cffccts of nicrNinc rHr IhC inttantanfrNlt frxce-veh,city rclalirms of Ihe intacl Icl1 vcnlriclc in chrtcd chctt dugs Nicoline was adrninitlcrcJ with anJ withuul prior "a adrencrgic blockade with propranutul in an allcnr'rl 146 dclcrminc whether Ihc myrxardial eRccts of nictNinc arc mediated IlurruEh Ihe rc Icase of nurepinchhrinc. Results show that nicotine augments mycx'ardial amtraclile statc as indicated br an incrcase in Mdh the furce and vckxdy of shnrlcninR I~indings ncNed when hela-adrenergjc Mr><kade hrcccJcd nitvNine adminittraliun suggest that pntpramdrd impairs the norcpinclrhrmr likc clfccls of nicotinc (xr the myucardium while it cnhances Ihc pcriphcr:J vasr+presurr action (ol nicotine. f uri, 1'. S, Alarny, 1) and RinR. R. 1. Innrrruf .r/ (7init al 1'lmrmaoluRy ond the Journal u/ New 1)rugt R(5) 245- )(11, 196R. Othrr Rrnnt.rrr: ll. S. f ublic lkallh Service, Michigan Ilcarl Atsrciatirrn, American Medical Association Education and Research Frrundaliun, and 1)ctmit (icncral Ilospilal Research ('orporaliun. Frtmr the 1)cparlmcnt of Medicine. Wayne State University SchrKd of McJi- cine, Iklroit. F.VALl/Al ION OF MYOCARDIAL FORCl:-VFI-()('I l-Y RI?I.A'11ON IN ('LOSl:b-('1 ILSf IXX;S 'fhe furce-vehxily charactcrislics of the left vcnlriclc in 35 chncd- chcsl ancsthclitcd dugs were sludicd by means of a slrain-gauKc catheter asxmhly. Instant:rneout velocity of shortening wat dclcrmincJ at an isri- Ienglh (.rtin/ un the curve of fiber shortenin6, by drawing a tangent tu the curve relating height of dc/kclion to time. Ventricular pressure relaled in lime lu thc isrrlcnRlh pptinl was uad as a measurc of force. Inslanlancuus fracc-vehKily relations at a constant nrusck length could thus he stuJicd. Alterations in afacrload induced by inflating and deflating an intra-aorlic balloon and by mclho taminc kd ta rcciprt+cal chanFcs in frace and vehKily. Ptsitive inrNrr>(»c dru(Cs, i c., epincphrine, mxcpinephrinc, and isripnNCremd, on the other hand, shifted llte force-vchxily curvc upwatds, ur upwards and to the righl, indicating either an incrcatc in vchKily :drme or an incrcate in fnrce plus vehmily, resl.eclivcly. '1 hctc results Innnted tu an augmentalirm uf the contraclile state of the heart. Itcta adrenergic hhxkade with pnq+ranuhJ Icd to a dcclinc of twrth forcc aud vchk:ity. Puri, 1'. S and RinR. R. 1. Arnrriean luurnal u/ l'hy.sLrl.rRy 214(h)1271.127'), 141iR Othrr Rrnnt..rr: 11 S('uhlic Ilcnllh Srrvicc, Michyg:ur I lcarl AstrK i.uiton, Amctican Mcdi.:d Assrrcialirrn Udutatirrn nnd Rcscarth I uunJ:rtiun, enJ Ikhrrit (:cncral Ihrslrital Rcscarch ('orprtratiun. Frnm thc I)cparlmcnt of Mctlicine, Wayne State llniversity Sclirwrl uf MrJi cine, lktruil. 33

LUII-ISUEN'LYMIiS IN INFARCTIiU IIEARI' Ml1S('l.li Myocardial infarction was pnKluccd in 20 drrRs fnr Ihe purprrsc of studying Ihe e0cct (4 coronary artery occlusion and myocardial in!arction on the 1.1)tl isocnzyme pattern of the ischemic heart muscle N.IlrrwinR infarction there was a siRnificant change in the number of Ll)II i-.nzymes in the ischcmic liuue. In normal dog hearl muscle l.l)II displays unly three isozymes, whcrcas in the in(arcted heart muscle all five isrrzymcs can he observed. The qualitative changes in LDII t>t infarctcd heart musrle were accompanied by Quantitative changes (n LDIa activity in the ischen ic area. Activity of LUII declined following coronary occlusion and dirninshcd to 219G of normal kvels ten days afler in(arclion llsis diminution is in put due to  rekase (if l.1)1I into Ihe coronary sinus blood and in par: due to inactivalion of the enzyme tx altcred enzyme kinelics accumpan/inR the changes in isoryme pattern. Gudhjarnsson. S. and Ptivcr, I). M. (Rinir, R. 1.) l.i/r SG ienr rs 7:621 627, 1968. OOther Rrnnturrz 11. S. Public Ikallh Scrvice, Michigan Ilcart Assrxiation, Amcrican Medical Assnciatinn Education and Research Foundalion, and Iktroit (kncral Ilrnpital Research ('r-rprrraWm From the Ikparlrncnt of Medicine, Wayne State University School d Mcdi- cine, tktroit. CNS IiVOKfU C(1RONARY ('IIANGUS AN11 ('ARI)IA(' ARRIIY?IIMIAS AN11-ARRIIYIItMI(' 1'f(()1'FRIIFS l)f MC.IIUrAMAII: Cerehral mapping of ncuroanalomical hxi having jurisdittion over coronary blood flow and other cardi«lynamic altcralirms has la-cn accom- plishcd in unancsthetizcd fiuser drrRs. (N.scrvatiuns bascd on 1'/ success(ul eRpcriments in adult doRs of both uRCs show Ihat, of Ihe 1,977 discrctc (xoints stimulated in the tcknccphalon, dicnccphahrn, rnescnccphalun and metencephalon, 7R1 cvoked changes in axrmary blood nnw, aortic- hkxxl flow, aortic blood pressure, hcart tate and myocardial tension. 'I hc highest crmcentzation of positive cerebral points which elicited cardiuvascular changes was found in the mescnccphalon. These expe rimental resulls appear to implicate discrete cerebral hxi with the productirro uf specific disnrdcrs of cardiac rate, rhythm anti cunduclinn. Other c. `xrimcnts with mebulamale shuwcJ this drug hr tie an c0ective anti-arrltythmk aFcnt aRainst Ihosc autonomic end c/lccrs evoked by clcclrical cscitaliitr of the reJ nucleus and/ur its neural cunncclMrns ('orrult, A/. N, 1r., I.yun, A 1: ,(irrlirnko, R. I , hunst, M, RcnF, I1. V, Jr , arN1 Vrud, 1). II Arz hircr Inrernurrunufr dr 1'hornwt oJyrwrnir er Jr I hrruprr 17 1(2 ) 462 474, 1968 Orl.rr Rrnnr.rr.: Wallacc 1.slMUalorics and lhe Merck Inslitutc (ur *lhera- pcutic Rcscar(Il Frorn the fkpartmcnt of Medicine, The Drookdalc Ilrrspilal ('entcr; and 14e Ik•parlmcnt of Analomy. State University of New York. I)uwnslate Medical ('cntcr, flrooklyn. Itll'I.ANE ('INI:.AN(:I(KiRAP111C UIiTI?RMINA-11ONS (/1' Llil'I' VIiN'1 Rt('III.AR FUNCf IUN: 1'RESSURE-VOI.UMI; RI:I.A'rI()NSIIIPS (nslanl lr.instant changes of left ventricular volume in ntan were mcasured using a biplane cincan6iocardiosraphic technique. '1 he results of prnl-nMrrlem studies in 13 human hearts and of studies in six patients with various forms of heart disease are presented. Nincty-sevcn vulunu ubscrva- liuns uver a volume range of 30 to 150 cc were recorded in the 13 pust- monlcm hearts. (N the six Patients studied, one had no valvular disease, one had patent ductus arlereosus and a vcntriculat septal dc(ect, while the remaininR four patients had valvutar insufficiency and/ur stenusis. 1'ressure and vulumc were related for the construction of pressure volume hNrps and the tkterminatioo of the klt ventricular pressure-vrAumc work for e~'cction. ('nmparistm tr( pressure-volume work determined fronr Ihc IrMrps and sUuke work calculatcd from conventional laboratory techniques shuwcd that Ihe dctcrminatiun of the pressure-volume work was more infutmalive Ihan the conventional calculation (if stroke work. Racktcy, C. E., lkhar, V. S., Whalen, R. E:. and Mtlnruih, fl. 1). Amrricmr Ilrnrl hrurnaf 71(6):766-779, 1967. Other Rrnnt.rr.: National Institutes of Ileallh, American Ilcart Assrxia- lion and l.i(e Insurance Medical Research Fund. hr+xn the ('ardiovascular I.aMrralnry, Ikparinunt of Mcdicinc, 1)uke l)ni- vcrsily Medical ('cnter, Durhsm, N. C. IN('RIiASI'1) StIRVIVAI, WITII f'ROI'IIYI.A('lIC (11I1N11)INIi AIAUR IiXI'VRIMI:N I A1. MY(X'ARI)IAI. INUAR('I I( )N lixperimcntal myrrcardial infarction was pnaluccJ in (,1) farm piys by Rradual cnrunary rxclusirm with an Ameruid conslriclor placed arounJ the Ic(t antcrior dcsceiMlin6 coronary artery. "1-wenty animats were treated wnh 10 mg/kR/h hr of yuinidine (an anli arrhythmic agcnt). Icn with S rng/k/./h hr, and ten with 2 S mR/ kR/6 hr fur a lulal Ix•rirKl r>< 72 huurs I wcnty animals scrvcd as crrntrrrls Scrum (IuiniJinc kvrls were mcawrcJ al h hour intcrvuls SiKnihcanlly irxrcascd survival, wlrcn .onrparcd tn r4rnlr4d%, was oha•rved in Ihrr.c aninuh Ircalcd with S and 11) mR/kl;/fh hr rrf qtnmJinc, but nul in Ihrnc rcccivinR 2 S mp/kR/h /rr. (tuJcr Ihr rlc.rrilK:d c.lw•ti mcntal cundilinns, dc"iprcd to causc a rcpr4Kluirt.le, t irn.nr"nt int,u,lu"u, yuinidinc Ircatrrn•nt in niMrlo.ic and well tidcratrJ Auacs signiliranlly uw t'tcascd survival Vurllxrnuuc, thcrc is n du.e Icvcl hclow w/nrlr thn cllc.t is lost Whcthcr Ilic results uf this s1uJy arc •rpphrahlc lu ru,rn in I,rcvcnr ing suddcn Jc:rth is unknuwn 35 14

1 r Ilurst, V. W., 111, Morris, 1. 1, )r , Zefl, I1. 1, Ilackcl, 1) II and M(lntush, 11. 1). Circulation 36(2):294-303, 1967. Oth.r Rrnnfor.r Natilmal 1leart Instilutc, John A. Ilarlfnrd Foundalion and North Carolina Ilesrt Associatiun. From the ('ardiova+cular Laboratory, Department of Medicine, and the Ikpartment of Path/dosy, E)uke University Medical ('enler, I)urhanr, N. C. PRF_SSIIRE ANI) VOLUME CIIANC;ES OF TI lE: LEI'f VEN7 RICLE IN A('l1TE PIiRICARf)IAL TAMPONAUE In experiments with eight do6s, acute pcricardial lamporna 1e pro- duced the eepecled hemodynamic alterations, namely, depression in cardiac oulput and elevation r>t left vcntrkulsr end diaslolic, right alriat, and perK•ardial pressures. I/eart rale was not significantly altered. t-ell venlric- ular end-diastolic volume also behaved in the expected manner and was found to be siRnificantly reduced. The phasie pattern of left ventricular diastolic filling was not altered although the rate of early diasl/>f,c filling was reduced. l eft ventriculsr end sysil>fic vdume was not significantly changed. Although left venlricular funclion was shown In be tb'presscJ by significant falls in ejeclion fraclion and nxan systolic ejection i ate, the relati/mship of Ihese parameters to myocardial cunlractility was eanmined and found, under lhese esperimenlal condilions, tn he inconclusivr. Craig. R 1, Whdcn, R. F.., llchar, V. S and Ml Inrlrsh, !l. 1). Amrril'an Journal n/ (-ardadnRy 22( I) h5-74, I VbA. ()th.r Rrnntur.r Natitrnal Ileart Institute and North Carolina Ilcart Asso- ciation. ' From Ihe Cardiovascular I,ahlxalory, Ekpartment of Medicine, Uuke Uni- versily Medical Center, t)urharn, N. C. PIION(X'ARUI(X,'RAPI-IIC 1)ISCREPANC'IES IN TIIE ASSE:SSMENT OF MITRAL SI ENOSIS PhonocardioRraphie, cardiac calheleriratilxs and surgical data are an- alyzed and compared for six patients exhibiting milral slenosis whose phonocardioRraphic findinRs failed to predict the milral valve area as esti- nraleJ by the other two methlxfs. 7 he corrected Wells' indices (01 minus 2 OS times) ranged from - 5 to I I and were discrepant to actual valve site in all sis patients Analysis of UI and 2 OS intervals usually permits a reas/rnable estimate of the degree u( stemnis of the mitral valve. Iluw- evcr. the intervals are altered primarily by pressurc changes. Altcralil,ns /,f other factors such as flow, valve slillrsess, snd regurgitation may resull in discrc'nncics c>f these mcasuren,ents As dcrnlntS lralcJ in Ihcsc paticnts, the Wclls' index is not an aln/Aute crilcrilNt ld Ihe scverity 44 rniiral {IennSi7. Racklcy, ('. E,('raiR, R. 1, 1<1l lnroJr, ff 1) and OrRain, 1: . S Ar/ lucrt of Intrrnul Afrdn inr 121 SI1 S1, 1968 16 Ofhe . 6rnntor.: National Inslitutes of Iledlh, Amcrican Ileari Associa- tion and I-ife Insurance Medical Reseirch Fund. Frurn the Ikpartment of Medicine, Dukc University Medical ('enter, Uurham, N. ('. NORf:PINIiI'IIRINI:- AND IIEPARIN-1NUUCIiI) C'IIANGIiS IN PLASMA fRFE FAlTY A(.'ll)S: A COMI'ARISUN Ii1iTW1&.N PAIII:NI'S Wllll ISC'fIf:MI(: III:ART I)ISI:ASE ANI) N()RMA1. YOUNG AI)UI:IS SiR nrxmal subjects and six patients with  history of nryocardial in- farclion were given rwxerinephrinc (1) 2 rg per kilogram per minute) and hcparin (1(X) mR inoravcnausly) in an cRort to determine wlrclhcr Ihe druRs' r spective lil.ulytir eOecle would reveal changes in plasms free /atty acids in tlre diflerenl subject Rrtwpq. All studies were done after an overnight fast and an overnihht smoking prohibition. Free fatty acid increases in plasnra after mrrepinephcine occurred more slowly and to a significantly Icsscr degree in Ihe coronarr group. This diminution was particularly apparent in rcRard to pa:milokic sciJ. The heparin scnsilivc lill/d fMMd in the clxunary Srlrop eemlzined significantly nNxe palmiloleic acid than the rnnmal; and (>tl minutes after injection, significantly more slcaric aciJ re- rnaincd in Ihe plasma of Che crxrxrary subjects. I leparin was alut Kivcn five minulcs after norepinephrine infusilxr was stopped '1'en mimrlcs later tlrcre was a significantly 6realec increase in the two saturated acids, myridic and Palmitic, in the coronary group. Thest findings seem to support previuus rnvesliRaliuns which have flwnd increases in the more salur:rlcd fatty acids in the plasrna uf patients with coronary artery disease anJ indicate Ihat this is a rcOccli/xr of IipoRcnesis from carbohydrate. Rulenherg, 11. 1.., Schwartz, 11. and SrrfuLY, l.. A. American Ilrart Journal 76(2):11f3-192, 1969. OOther Rrnnfor: 1/. S. Public Ilealth Scrvice. From the Ik partment of Medicine. Temple University Ilcallh Sciences ('enter, Philalklphia. ('ORONARY AR71?RY DISEASE ANb 'I III: CUN('1:1' fOF CARI)IAC FAILURE In this discussion papcr, a plea is matk to abandon tile ahslracl, n/rn- upcratiunal term heart failure and to descrihe the ways in whuh the hr:ut functions abnormally. Such an opcratiunal apprl,ach clcarly shuws that any lyl•c of failure clinical, hinphysical, f„lMitcmital, m/,lccular ucty Lc presenl in Ihe alnence of eonPestive heart failure, a lyl.e that reyuirrs Ihe pnrtiril,ali/wt ld ealratny/M:ardial (act,us. I-orrlhcrrunre, Ihc ul,crariia,.ll apl,raianc tlrarly indica/cs that one cnrnn/,t dt.tinpuish Ihc lau.c lil,m cOccl without knuwlcdKe u/ Ihe IcmfM,ral rclaliuns of Ihc Iwl, Ilctauar /d viciuus, invululcJ caust cflccl-cau.e circlcs, dcath is usually nnt causcJ by eichauslilro uf Ihe hcarl hut hy eslracardiac faclurs that arc ini,nnl,.inhlc with life. 'tlre intcrrclaliun%hiln of Irllra anll c111ran1ylK:IrJ1aI IaltUrS I,ar- 37