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t 312 Preliminary Communiration CUMiJLATIVE EFFECTS OF LIFETIME PASSIVE SMOKING ON CANCER RISK* DA1E P. SANDI.ER: A1.c.EN!J. WILCOX R1cH,1RD B. EvERsoN Epldnniology Brancb, Blb+ncrry: and Rirk Asreufnenr Pragrarn, Irttrtr'a>tal Iruttrutu of Emmormeextal Health Scie>tcas, Reuarfh 7rianglt Park, North Carolina, USR Summary Cancer risk from cumulative household~ exposure to cigarette smoke was evaluated'in a case-control study. Overall cancer risk rose steadily and significantly with each additional houaehold member who smoked over an individual's lifetime. Cancet risk was also greater for individuals with exposures during both childhood and adulthood than for individuals with exposures during only one period. These trends were observed for both smoking-related and other sites. These findings are preliminary, and must be eonfirmed with other studies:. Nonetheless, they suggest that effects of exposure to the cigarette smoking of others may be greater than has been previously suspected. IATTRODUCTION INCREASED risk of respiratory illttess in ehildren,l'3 changes in respiratory function in children and adults,`,S risk of childhovd!tnmours," tmri Tie;k of lung cancer and possibly other adult cancersa" have all been reported as possible effects of exposure to other people's cigarette smoke (passive smoking): Adult cancer risk from childhood exposure to parents' smoking has also been discussed.'6•]s These studiess considered the independent effects of ezposure in one period to cigarette smoke from only, one source, even though individuals may, be exposed to a number of sourees over their lifetime. •Some.of this m6rcrial atrn premted at the 6naoal meetnna of the socicty.for Epidtmiolopc Raearcls, Junr, 19A4, Houseon, Tesas USA. THE LANCE-r,FEBRUARY 9;1985 In a study of adult cancer risk rtlat'ed to parents' smokingl s we collected data on:ezposure to cignrette smoke of not only parents, but also spouses and other household members. In the present study cancer risk in relation to cumulative passive exposure to cigarette smoke was estamined: W e didborcollect data on exposures outside the home, but were able to consider whether cancer risk increases with the number of household' members who smoke. METHODS Study methods have been reported elsewhere.13:15 Cancer patients were selected from a bospitahtiased tumour registry. They included all those with ancer diagaoaed between July 1,,1979, and March 31, 1981, and assumed to be alive on March 31, 1981. Patients tartged'from 15 to 59 years of age u the time of diagnosis, , and all ancer sites except basal1cell cancer of the skin were included. Patients were restricted to age 59 and younger to ma=i**++v the likelihood of tmtertnl amokirlg, since few women were smokers before 1920. Of 740 eligible cancer patients identified from the tumour registry, 107 (14°1u)i died before we could contact them. An additional 115 (16%) either refwcd to p.rticip.te or could not be contacted. 518 (70°76)'patienu completed questionnaires. Control tubjeas were cancer.free and of the aame race, sex, and age (t5 years): as patients. They were friends or acquaintances of p.tients (nw309) or were randomly selected by systematic telephone sampling (n - 209). Patients and control stlbjpcts were also similar in occupational category and smoking habits. Analysis was restricted to individuals who lived with both natural 'parents for most of the first 10 years of life. Results are reportedifor, 369 patients and 409 control subjects who supplied information about the amoking habits of their spouse and parents. Information on exposure to cigarette smoke was obtained by taeans of a structured questionnaire that was sent to all subjects. Another questionnaire was sent and follow-up telephone calls were madrwhen a response to the first questionnaire was not obttined:. Childhood exposure to cigarette smoke was assessed from questionnaire reports of smoking histories of parents and informauon on other household members who smoked; Subjects were considered to be exposed during childhood if! one or both parents smoked'cigarettes in the house before the subject was 10 years old or ifone or more other household members smoked during that period; Passive exposure to cigarette smoke during adulthood was estimated from the number of years ofmarriage during which a spouse smoked. Subjects were considered to be exposed ifahey had a spouse who smoked regularly at any time during the'u marriage.. Active smokers were defined as those who ever smoked as many as 1 cigarette a day for as long as 6snonths. It. H. WIEDMANN AND OTHEILT: REFEiENCES 1. M.il. a, t.ma DJ.. t.anceern .Ja.ii: Suppeeom m1iw w.wdped.iJ acuee iefeniau Sry.enu. Sawwor 196.T, laa: ao-e l. I.:Ne.We.DI, Hdmn AT, W.oal AG, rwboU..l.wue eucu6ee fs n9u ev.l 6epaitu.. C7m Err lwwrus/ 197%. ah a 7-1a.. 3. W imb Jx, PenonoJt., Alpe.rt E, ladh.e6ee]U. Cst4eedrm6 im.ooinr mnvee d ehaoie 6eptier. f C6, /.em 1975; aa:921-29. 4., Mto M, Mvsauebi Y, Mome T, ,Yr.eeoro S, Mor.ow.S:. &udw m the wDPopuWeieo dl4nctiae d PcipAer.l lrmyleeTtee,.d inhibuar m PHA wLoulerias emtiy, m the arumd paiem sL Ii.a diw- llwot..w.~7q 1975; 3a:.3a7-13. S. Nikw M; Mueauebi Y, Meme T, Yowmoto s, Moeir.. S. Seudw m.a iahidtony f.ctu[ ro pEpoatem.a{Ibtiniwiedund:ytaploc7u oamdamam. feond in W e .cnmdpnYmn.ial.rtiar li.er diern. da. }Jq.+.G.un+us.1197a; fa: 335-43: 6n araty N, aa{ PA. SeruamliEiterr r.eoee (SIF) mp.cieaa .itE ocu.e d efvmk brcpriti. d Yhor c4aid.qei6ooa. Ci. EaP lwwrd 19176,09 40-49. 7. NeLon DS, Cnni IU..Hmnat,l 5nonm%ueacioa Irmpba7ee ersfsmaae.NY. AfWV .1976; 21: 261-341. a..l.e.r GA, Cluui PV. T!e immrmopnhoacmiw dtirerc 3DV induaf 6+v d"w.... SP.iWr..S+.i.Iwweee.p.e6./.19a1; a, 639-S9. 9. aratia NW, SeLRmpf-DecYu GE, at6d1 CW, tiera PA. Ismeeoapt.ato+t wtnm6,nao in.vd 6eRUirc'r. n.. titnher rLo.c.ervoiemn dtvumie~ 6eeer.fSIF7 . r d6~areoqad aokvk Hya.bay 1963; >s 647-SS. 10. hottia NW,. Dva PA. Immam.app- .eum6tmI mv'vd t,epaim. L.. Chvaeeairniee dneum lebitiltm BetoRel whmfh.,Re amo+cu..evf N; HJP.rd~ 1903; k 63a-96: I l. Y.mir Z, Lakic ML, Cwerio M, Sfmir ASM. Sarom mLiMton d mitoaso-uducedT eelU prolifemtioe (StMTP).rweietedmth pvaaea::6apnoctlluLrmim7,aftc .ie.l bepaoitie (.ben 9.6.11) :IV: Iaarn.ooo.1 ceogee dimmuuolOry, P.rr,19a0.12. Gnutr W, anni{ NW, ScLomew H. fr6eovGj aer6 PA. t®uno.uppreai.ew a+um factun in.inl9upaitum ltt..Prepw.ncrtlenoce dtoeem,oh;bUOrr.hctor d.erum ieAibitm f.nor in KUtee d clrmic lepu~ Hq.rrskp.19N; 6:15-19. 13. Suociu L, Cbtrirw D, Par.u N, aadu D; Dcjiu D, 6orpn V, Urnn5. CelNJir and Sumonl immuae mmifambaes ie.cveleqnier H**.C.,rtr.u.d 1962;.t9: 66;. 19: Sc6oeoenu H, W icdmem JCH, Ibll! W, et el. (.) C3.nideanl•7 in the tre®ent nf.~,f avtr.ue,l bepaituA tdomreed amroll.d vid. Heio.r.iaey 19M;t:. )H-35 IS. F+6.ner GG.~ Sehomeru.H,. Wedm.oe RH, et, al. Duanmait gif,aanci of O. qu.ntnnm determmnioa of 6epeenit a wrSee .e.ip= mtcnu d.d riroou \epo,aie a iefettim. ErR JCti. Mr+o1..1.19at; il:Sb5a. 'V N Is c46ra1 tmmuedop. IiHO. rd Jtq Sn 1973, se 696.. ~. . 17. NiN.en JP, tAeaicLem O,..Elliis P, « a1 IaoOeuce and ee.nioa of puswaoer of w Aunrdiaueiaeniopaisao.inlacueefrynitae4.Nopmmtde6reaoc6ep.urum fr • N.Eqf ) Md 1971; faf: ~~ 1157. W_ 18, haore G, Dmoico P, Aepnno G, laped6u I?, Sclinadi O. hnmeas du aesuen a. a ewit k a r 1979 71 f L i l 4 17-20 pr {A mu u e ttune . , c . ; ep.r o y : . . 19. aer{ PA,. amtia NW; Die leAeutwu iemmreauloti.a FJnoetn Rt d,e N, pseaaawucle:aeunnluna dn Vau.6epniua.. Md Khr.l9a2; 77: 619-24:. /w 20. 86ptpoo.TS. Immune rwpoewd ii.erdre:.aut ha.bwn uW t.p V ~o Asknees7 Hq.rs/s0 1963; 3: 767-66. 7ll aat PA, at.ai6 NW: Da Srruwiohi6rooa.6lxa Eiei der.Jyree V-.6epetar Lr6n M.rw Aer. 1904; 6: 361-69..

THE L.ANCFT, FEBRU rtltl` 9,1985 TABt-E 7-OVERALL CANCER RISK FROM HOUSEHOLD EXPOSURE TO : C]GARETTE SMORE Number of h'oue:holtl tnemtien who smoke 2 3 or more Cowt6itted6roup~ Patients 54 127 123 ' 48 Control subiects 99 161 97 34 Odds ratio ]i0 1,4 2-3• 2' 6'"t Acrme r"atsrr$ Patients 60 78 35 Control subjects. 38 73 60 25 Odds ratio. 1•0 1-4 2•2• 2-4•t NdRnnroken P.tients 32' 67 1 45 13 Control subjects 6] 68 37 9 Odds ratio 1•0 1•5 2.3. 2'8't •Statisticatly sigaificam differcates berween risk with specified atunberof esponues and with no exposure, pC0 • 05... tSoatiaioll~significartt X'' for trend, p<0 • 01. $Current smok'erssnd es•smokers. W e have found 13,15 that exposure to parents' or spouse's smoking eontritiuted independently to cancer risk-ie,,adjusting for one exposure did not alter the risk associated with the other. Thus we tssed'two approoehes,to measure the effects of multiple exposures: cancer risk was examined in relation to the total number of houschol& members who smoked, irrespective of when ~ the exposures occurred, and in relation to the period during which the exposures occZUrsd (childhood or adulthood only, orboth periods)'. Odds ratios were alculated and a chi•sqware test was used to assess statistical significance. A chi-square test for tinear uend was used to evaluate the risk with ineTeuing numbers of exposures in unadjtuted16 and adjtutedl7 analyses. RESULTS Cancer risk usociated!with exposure to increasing ntlm- bers of householdmembers who smoke is shown in tablt 1. A smoking mother, father, spouse, or I orr more additional household members who smoked during the patient's childhood or a spouse who smoked while married to a patient each counted as one exposure. The total number ofexposures is the stun ~ of the individual'exposures. Overall cancer, risk increased signifitxntly with~ increasing numbers of aposures, with odds ratios rising from 1• 4 for 1 exposure to 2• 3 for 2 exposures and 2• 6 for 3 or more exposures. Statistically' significant linear trends were also seen when smokers and non-smokers were considered separately. Adjustment for potential differences in age, race, sex, and educational level did not alter thest trends. TABLE II-OVEltAI1 CANCER RISK FROM HOUSEHOLD EXPOSURE TO CIGARET7E SMOKE IN CHILDHOOD AND ADULTHOOD, Age period of tapo.ure No exposure ChildEood only Adulthood~ osly:}'i Both Patients 54 107 I 98 145 Control sabiects 99 ,I 124 72 98 Odds ratio. 1-0 $$$ 11 1•6 1 L•9 2•7$S 1•5$, -E=poaure too smoking mother, father, or other hoosehold rnember during childtiood. •f E:posuro. to smoking spouae. $Sutistically,significami diRereaces between risk with tpecifrede:pmstue.nd sso exposure, p<0 - 05. SSutistiwUy sigaificanrlioear trend: ooo ezposure,:ezpotasre in only otx time period, exposure in both time periods, x' for rrend - 23 ,7,.pG0 • 01. 313 We also measured cancer risk in relation to the period when exposures occurred (table 11). Risk rose by 60°rl% for individuals exposed during childhood only and by 50%a for individuals exposed during adulthood~onNy but was more than doubled for those exposed during, childhood an& adulthood (odds ratio- 2-7). There was a significant:linear trend in risk for individuals exposed in no, 1, or 2 periods. Again trends were similar for smokers and non-smokers and were not affected by adjustment for potential confounding factors. TABLE1l1iCANCER RISK FROM'.MULTIPLE HOUSEHOLD EXPOStJRES TO.CIGARETTE SMOKE: SiTES' WITH 15 OR MORE CASES' Number of ezposures. Site Number of':ases. 1 0 1 2 3 or trwtt.. Allaiies I 369 1•0 , 1i•4 2.•3 2•6$ Smok'ingrelatedt 115 1•0 1 P•8 3-0: 3•8$ Othcr~ 254 1•0 1•5 2-4 2•6$ Buccal rn•ity.and: I I pharynx 15 1-0 4•9' 5,1' , 2•9 Digestivetnct. 30 1•0 0•7 1•8 1,3 Respirasorytnct 19' 1•0~ 0+7 0-6 2-9 Breut. 48, 1•0~ 2,0 2-4 3-3$. Cervix 62 1•0~ 1•6 3•6 3•4$! Eye„br.in,, aad otherr nervous.system 29. 1•0 2-3 2-3 0-7 Thyroid 19. 1.0 1-0 3.-1 8-7 Leukemia and lymphoma 37 1-0 2-5 5•1 6-8$ •Odds.ntios are given. •}lnclirdesonl uvity.and.ptiarnyi, oewplnagus, partereas, respiratory tnat,., urinary tract, aad cervu. $Statisticaltgy significant linear trend.. Cancer risk increased with increasing numbers of household exposures to cigarette smoke for smoking-related sites and for other sites that are not thought to be smoking related (table III). Smoking-related sites included cartcers,of the oral cavity and pharynx, oesophagus, pancreas, respiratory tract, urinary tract, and cervix.ir,ls For smoking- related sites odds ratios for 1,,2, and 3 or more exposures were 1• 8, 3• 0~ and 3• 8, respectively. The trend for the other sites combined was also statistically significant but the risk was less than that for smoking-related sites. The trends for cancers of the breast and cervix and for leukaemia an& lymphoma combined were significant, but the trend for cancer of the respiratory tract was not. DISCUSSION If passive smoking has an efTeeZ on cancen risk the nature an& extent of that risk are likely'to differ for childhood and adult exposures. The clear overall trends found in this study might be associated with carcinogens present in tobacco smoke acting through multiple mechanisms at ditTtrent periods of life.. We found the risk of all cancers increased steadily and significantly with cumulative lifetime exposure to household members who smoke. This tren& was not altere& when adjustment was made for confounding variables. Our findings must be regarded as preliminary. Prompted in patt by experimental evidencetq we initially intended to measure the effect of transplacental orr early childhood exposure to carcinogens on cancer risk in ~ adulthood. W e chose to investigate cigarette smoke because exposure to this carcinogen is both crommon and measurable. The finding ofa cumulative lifetime risk from passive smoking was ttnexpected.

314 We collected information on most possible sources of eigarette-smoke exposure that would be encountered during childhood but the only adult exposure we considered was that resulting from the smoking of a spouse. We did not validate information on smoking habits of spouses but interviewe& more than ~ 700 relatives of patients and control subjects to validate the quality of parental smoking histories provided by adult offspring.. Study subjects provided adequate inforntation on parents' smoking, and the quality of these data did not differ between patients and control subjects. For adults in the United States exposures to cigarette smoke outside the bome may be important.20 Also the frequency of exposure to other people's cigarette smoke may change with age, with the peak exposure possibly occurring during a person's 20s.20 We did not take exposures outside the home or age-related changes in exposure frequency into account. Our data are limited by small numbers of any specific cancer site, byrersain characteristics ofour study sample, and by other features of our method.ll•15 No conclusions about the impact of passive smoking relative to the effects of direct smoking can be mad'e,,since the selection of friends as control subjects meant they were usually matched with patients on smoking status. We confirmed the quality of our data and ruled'out many, but not all, potential confounding factors. Although the passive smoker receives a quantitatively lower eZposure than the active smoker, that exposure iss qualitatively richer in many smoke constituents: there is 3 times as much'benzo(a)pyrene, 6 times as much toluene, and more than 50 times as much dimethyknitrosamine in a fixed volume of sidestream smoke in the gas phase as there is in cigarette smoke inhaled by the active smoker.ls The potential for damage from passive exposure may be greater than has been previously recognised. Our finding of dose-dependent cancer risks for sites not considered to be relate& to acti've smoking might be questioned because active smokers are also passively exposed. For some sites it is not clear in the literature if no risk from direct smoking,exists or ifa possible link has not yet been investigsted. For other sites, such as the breast, some studiess have found no cancer risk associated with smoking.2' One possible explanation for this discrepancy is that in studies comparing smokers with non-smokers, passive smokers are included in the non-smoking group. This would make it difPicult' to detect a small difference in risk due to smoking. Few studies have evaluated thc effects of passive smoking on risk of cancer at'sites other than the lung. Furthermore, there is little data available on the effects of transplacental or childhood exposure to cigarette smoke on cancer risk in adulthood. Data from biochemical i and experimental studies support our findings though many of these reports must be regarded with caution: There is evidence that non-smokers are exposed to potential carcinogens through the cigarette smoking of others. Cigarette-smoke by-products such, as cotinine and thiocyanate have been measured'in the blood, urine, and saliva ofnon-smoking adults, children, and fetuses exposed to smokers,u-TO and'there has been at least one report of raised levels of mutagens in urine of passive smokers n Greater activity of earymesthat metabolise bcnza(a)pyrene has been noted in placentas of amokersis)o and', even passive smokers.11 Similar increases may occur in tissues of fetuses, children, or adults exposed to smokers. Studies in laboratory animals provide evidence in support of an adult cancer risk from transplacental or childhood exposure to cigarette smoke, but this hypothesis has not been TtE LANCET, tEBRU1YRY 9,198 5 tested directl'y:19 Data from these studies show that many carcinogens, including those in~cigarette smoke, are active when administered transplacentally or during early life and may produce effects at lower doses than those required for adults.33" Some low-dose exposures which are not in themselves carcinogenic increase the sensitivit~ of exposed animals to later carcinogenic ezposures.17 In other experiments tumours resulting from transplacental and early postnatal exposures were not apparent' until the animals were fully developed and did not necessarily differ in site or morphology from spontaneously occurring tumours.32,39 This is consistent with our finding 47f raised~ risk for adult tumours at many sites. Future studies should include cancer sites not necessarily associated with active smoking and should take into account childhood sources of passive smoke exposure. Correspondlnce shoild be .ddrescd'~toD. P. S, Epldemiotogy: Branch, NIEH S, PO Box 12233, Ntail Drop A3-02, Re:uardi Triaoete P.rk NC 277p9 USA:. REFERENCESt. scbmli:r MB, Swn JM, Speiza FE. Ralfoctas for chiid4ord respireory dreaee.. The eRen of bon, finon ood bme en.ummranl izpowrm. Aw RftReP D_ 1983; 12ai 1038-4i: 2. H.rlcP 5, D.rna AM. lafmrcdm- to hspiut tmd mrema hmoito{. IArn 1974, 1 :.529-32: 3. Camcron P, Robcrt.oo D~ EAm ofhome mnroomeot toE.® ®otc m4mily,he.hh, J.App/ PiyrtAu/1973;, 57: 142-47. 4. Tqer IB, R'e,n STS Munox A, Roorrr B, Speittr FE. I to8i:uiiiasl.rody of rlie eHero of:mner,ul .motin8 on ptlmonuy funmoo. mrLildren. NE.E)) Msd 1%3;1N: 699-703: S. Vhite JR Frneb HF. Small.ir.on dyafuncuoo.in two-tonoienciwnioBy ape.eSto ro6.cco.mute, N,EiYr J.Md 1980; sss: :720-23. 6. Neurel Cl, Buck C: , Eften of waLrnB" dww8 pqeta.nq, ea eLe . rret of anar, itcdildren. J.No+I Ga.ealwa 7971; 47: 59-63. 7. Peoron<Martin'S, YuMC„Bewoo a, Hendir.oo.BE. N.eiaoo-Pouadt mdchlldhood bnm tumoun: A csesmrrd audy, fw+toe Ru.1962'; 42: 5240-45 8. Grulrerman S, d'.nl HH;,D.Loo4 ER, . Kimm SYS. Dtlhll I ES,FWtnr JM. Enruoomentil frcton ,n tbe atolocy of:rhs bdomyao.reomt to cLJdhood. J Nsrf ' Caww l.nr 1982; 68: 107-13. 9. Hinyt®c T. Noo.amolin/ ..ivn of bn.y moken b..e a hKher ruk af lunrooar. A study,from J.pan. BrMed )19'81, 2i2: 18Y85. ID. Trchopotulor D, Kalaod,d, A, Sporro. L, MrcASahon B: Luq nocer md pmve ,motm{ l+r J Gatw. 1981; 27: 1-4:. 11. BucYley,1D, Huru R W C, Doll R, Veeey:MP, a'iW.ms PT. Gr<oorrol study af the bosbonds of romen rnrh dyapWau a uremom.of tbe nma unn.!<wun 1981; u.. 1010-15- 12. Bro.o DC, Penin L, Ger>rr JB: C.ncu of thr ov.i: ond tLe oaiSnB hutib.nd. G+ Hw PAynno+ 1982; 241: 499-502: 13. Smdlcr:DP, Evenon RB, Wllcoa AJi P- .motuy indid,Loed ond onca rnk. A. J,Ep.dnw,ol.1985; 121:d7-48. 14. Coero P, Puke LC`, Fon,E.m E,.L. Y,.Haedul W..Pru.. makio8 ued lunr onna , la.cn 1983; u.. 595-97: 15. S.ndiee DP, E+erwn RB, G'Jco: AJ., Bro+der JP. CGmcer rau.duPohood frame.rly Lfe eryature totarrni Y®o40= (m preaq; . I6. Rahm.n KJJ Bmce 1D. Eyderniolopewlyue.nh a propammobk calcuJsnr..US. DHEW, NIH publicaioo no7A1649, 1979'. 17. MroteI N. Chi~.quve teso irD.oee depee dtmadoeo:Eaesio. ofMaoul-Hamaul prondun. J,A. S.r Ae+a 1963; N: .69o-700. 16. United 5uto tkputment of HealdD eod Humem Sernns. The bdth mmequenca of emokint-A eepnrt of the Siv{an Genv.l. DHHSptbliotuo nc (PHS) 82-50179,1982. 19. E.ersoo RB. titdt.iditele tr.mpl.cmtaay eirposed totrtan.l tmolin8mey be a inneo.edc.oce ri.l' mtlult hB. L+ur 1980; ¢ 123-27. 20. Friedm.o G D, Perirri DB, Bo.ol !RD! Pr-Umc od cortsLreof pri.e rmd+nl. An,JRi6Y,r }IrdnA.1983; 7!: 401-05. 21. Ro.enber8 L,.Sc6.irr8I.PJ, K.ufm.n DtQ, a.1; Brean onea amd npnare ®olios. N EKl J Md 1964; ? 19r 92-94.. 22. Ba,ome SF; Kuhart BR Kuhnrn PM. Aeesc AL. M.rcreel p~.e wolto{.od feu1. .num elvaquure Ie.ds..AetJO6wr G3+~ 1982i 166i:787-91. 2J. 5mirL N, Awrco J. Roaee ClTenury,®ak,nt hy rhe feru. Lam 1982; i: 1252. 24. m41d NJ, Barebam J, Baiky A,1t+,cLie C, Haddo.JE, KnYBLh G. Urirrry.connoeoe a rwrloof :bruthin8 tMhn peopli r. to6occo emo\c. li.m 1984; i:.23fH 31. 25. Gteenbaf RA, 1Lity NJ, Etttl RA, ladc FA.. Mmunct the aparvn of:mhata to roEao ®oLe: Nicaihe aodcuiniee ie urioe .nd rli.a. N EVr JMd 19f4; slt 1Q75-78. 26. MnnJmn 5„T.mdrrto T, ttiuoe N, ee .1.: Efraen dsorimnmeoW to6occa®oYe o0 oriony,rnatine aaetiooihnoemolenEndenct for ps.e tmoba8. N Eq(J A4d 196f 711: 828-32, . 27. Bo RP, Tbeu.e JLG; Her>denaePT: E:neoon dmutnsae to liumao uritxafte.t poriw tonotin8. C..or. Lteun 19113; t.: 85-9a i 28. rAekb RM,.H.nuom YE,Cooury: AH, Prypen PJ, Fmnc.M.: CKvene ookrn6.. StimuLrory: dfect, . oo menboli® of 3, 4•.bensprrme by tazymnm bum.o plocema Soev1.968,1Mr 541-42:. Rrfnorm m.riwred ar foor of wecr poN