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[Kloepfer Ny Class Actions Dep. Exh. 128 Tobacco Institute Pamphlet, "The Cigarette Controversy," British Journal of Cancer, "A Study of the Comparative Carcinogenicity of Cigarette and Cigar Smoke Condensate on Mouse Skin," Davies R.F. And Day T.D. Proceedings of the American Association for Cancer Research, "Effects of Saturated Solutions of Tobacco Tars and of 9,10-Dimethyl-1,2-Benzanthracene on the Hamster's Cheek Pouch," Tabah E.J., Gorecki Z., Ritchie a.C., Skoryna S.C. Symposium on Chemical and Biological Problems Related to Smoking, "Experimental Investigations on the Possible Carcinogenic Effects of Tobacco Smoking," Druckrey H. Z. Klin. Chem. U. Klin. Biochem., "Nicotine and Arteriosclerosis: an Experimental Contribution to the Influence of Nicotine on Fat Metabolism," Schievelbein H., Lalternative Hypotheses, Causationondong V., Lonpa-000465 Dong W., Grumbach H., Remplik V., Schauer a., Immich H. Arch Environ Health, "Effects of Cigarette Smoking on Dogs," Hammond E.C., Auerbach O., Kirman D., Garfinkel L. Arch Environ Health, "Pulmonary Neoplasms," Auerbach O., Hammond E.C., Kirman D., Garfinkel L. "Many Workers Still Face Health Peril" [Quotes Hammond Ec], New York Times, P. 1, 20. Publication, National Heart and Lung Institute, Submission, Hearings Before a Subcommittee of the Committee on Appropriations, House of Representatives, P. 281 Clinical Research, "Clinical Epidemiology: Cigarette Smoking and Lung Cancer: the Problems of 'Detection Bias' in Epidemiologic Rates of Disease," Feinstein a.R., Wells C.K. New York State Journal of Medicine, "Lack of Correlation Between Antemortem and Postmortem Diagnoses," Prutting J. Supplement I to Circulation, "Coronary Heart Disease in Seven Countries [Page I-106]," Keys a. Supplement I to Circulation, "Coronary Heart Disease in Seven Countries [Page I-188]," Keys a. Journal of the American Medical Association, "Coronary Mortality: What Is Going on?" Walker W.J. Hearings Before the Committee on Interstate and Foreign Commerce House of Representatives, "Cigarette Labeling and Advertising - 1969," Testimony of Dr. Victor Buhler. Department of Public Health, Tohoku University School of Medicine, Sendai, Japan, "Cancer Mortality for Selected Sites in 24 Countries, No. 5 (1964-1965), Segi M., Kurihara M., Matsuyama Transcript of News Conference, Report of the Advisory Committee to the Surgeon General of the U.S. Public Health Service, "Smoking and Health," Terry L. Press Release, National Interagency Council on Smoking and Health, "Statement of Emerson Foote, Chairman, National Interagency Council on Smoking and Health," Presented at Meeting of the American Association of School Administrators at Atlantic City, Nj, "Cigarette Smoking in the High Schools," Horn D. Hearings Before the Committee on Commerce, United States Senate, Eight-Ninth Congress, Pages 123-124, "Cigarette Labeling and Advertising," Hearings Before the Committee on Commerce, United States Senate, Eight-Ninth Congress, Page 133, "Cigarette Labeling and Advertising," National Tuberculosis Association Annual Meeting, Chicago Illinois, "Emerging Anti-Smoking Activities of the Federal Government," Terry L.L. Actra Genet. Med. Gemellol., "A Twin Study of the Influence of Smoking on Morbidity and Mortality," Hauge M., Harvald D., Rein D. [With Attached Memo by PM Dated 1/4/71] Dis. Chest, "Physicians' Attitudes Toward Their Involvement in Smoking Problems of Patients," Green D., Horn D. Hearings Before the Committee on Interstate and Foreign Commerce, House of Representatives, Ninety-First Congress, "Cigarette Labeling and Advertising - 1969," Statements of Williams a.C., Brewer L.A., Zeidman I., and Sommers S.C. Medical World News, "A Letter From the Publisher," Cohn H. Monthly Vital Statistics Report, "Births, Deaths, Marriages, and Divorces," U.S. Department of Health, Education, and Welfare American Medical Journal, "Mother's Cigarette Smoking and Survival of Infant," Yerushalmy "Study of the Biological Characteri]

Date: 1974
Length: 341 pages
TIFL0305350-TIFL0305686
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JD-080326
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Brody, J.E. 1
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1974
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368
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Doj Civil
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01 Sep 2004
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sbh45a00

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Statements in this booklet are fully documented. For a list of reference sources, or lor lurther inlormation, write: THE TOBACCO INSTITUTE 1776 K Slreet Northwest Washinglon, D. C. 20006 1974 0 THE CIGARETTE CONTROVERSY TIFL 0305350
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Preface 1 This booklet is presented by The Tobacco In- sOtufe in the beliel that full, free and inlormed discussion of the smoking and health contro- versy is in fhe public Inferest, and irt the con- viction thaf the controversy must be resolved by scientific research. For many adults. cigarette smoking is one of life's pleasures. Does 11 Cause illness-even death? No one knows. The case against smoking is based almost entirely on inferences from slalislics. The "con- venllonal wisdom" about smoking came Irom judgments expressed by commillees of doctors in England and the U.S. In our country, anti- smoking organizations pressured the govern- ment to endorse these judgments. Never before (or since) had a committee "discovered" a single "cause" for so many diseases. A number of respected scientists do not be- lieve a causal relationship bebveen smoking and illness has been eslablished. Others believe that it has. 11 smoking does cause disease, why, after years of intensive research, has it not been shown how this occurs? And why has no in- gredienl as found in smoke been idenlilied as the causal factor? 1 T q0i07OJ - TIFL 0305351
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some divine Intuition or were not telling the trulh." 24- Ssld another pathologist witness: "It is not possible, grossly or mlcroscopically, or in any other way known to me, lo distinguish between the lung of a smoker or a nonsmoker." 02..,+ Later, to illuslrale an environment story, a medical news weekly Iried lo find a"clean lung" photo to contrast with the darkened lung of a 4&year-old man who was born and died In New York Clty. Said the magazine: "Only by photo- graphing the lung of a four-monthold infant who died of epilepsy did we find Ihe expected contrast."~fr Smoker's lung? Yes, yoti II hear of it now and then, even from those who should know balter. It's handy, just like the "300,000 excess deaths" and the "100,000 doctors." But it is hardly truth. Thus have critics of cigarette smoking con- ducted themselves. adopting aggressive post- lions, reaching for the most sweeping and dra- matic clalms, often beyond statistical orscienlific fact. Smoking and Women You've become accustomed to seeing maga- zine and newspaper articles which say that smoking can harm your unborn child. Studies do show that smoking mothers, on Ihe average, have slightly lighter weight babies. Yet with more women reportedly smokinggIi~fant mortality rates keep reaching historic Iow5`'~ome studies . have shown that the lighter babies of smoking mothers actually have bettet survival rates than similar weight babies of nonsmokers. 27-Ig-a4, A suggestion thal smoking may not be the cause of slightly lower weights among newborns came from a California study of more than 13,000 mothers. Some of them began smoking after their first pregnancies. The babies they bore he/ore they were smokers also tended 10 be Jighrer in weight. 30, Thuss thero mny be other, more significant differences helween groups of smoking and nonsmoking mothers-age, economic status, employment, race, diet and many other char- actelslics that could affect Ihe oulcomes of pregnancies. Many Contrasts Smoking and health statistics have been built up by comparing smokers and nonsmokers. But when large numbers of people are sorted into two groups this way, are there no other differ- ences between Ihem? Dilferenees which might accounl for contrasts in health patterns? There are, indeed. say authorities who have studied such things. Some of them are sur- prising. Smokers generally are more commun tive. They are more creativ more energet drlnk more colfee and IiquA~~arry more oft prefer spicier a_ny sallier fodv. They ta 9, part more in sport~nd change jobs often~r° They are more fikely to have parents wilh heart disease and high blood pressure!35! These and other findings, accumulating in the medical literature, raise Ihe question of whether smokers may have higher illness rates because of the kind of people they happen to be. Science has learned that a blueprlnt of our consliluUonal, physical and chemical makeup Is laid down at the moment of conception. This Is genefics and, as Ihe saying goes, we cannot choose our own grandfathers. The blueprint is still fuzzy-we do not know, for example, the 8 9 ~_ 0h21U7p,9
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Those who consider smoking a menace, rather Ihan an enJoymenl, have acled as prosecutors, lrying to convince the public they have an air- tight case. But isn't Ihe "jury" entitled to some serious doubls, ror example:  Smoking cannot be the sole cause of any ilb ness, because in every case nonsmokers are aflllcled too.  Research suggests that because a palient tells a doclor he smokes, he is more apl to be diag- nosed with an ailment "associated" in the familiar slatlstics with smoking.$  Those statistics themselves are shaky. In cases of fatal IBness. causes are verified by autopsy in only about one-litlh. As one expert says, "meaning/ul morlalily stahslics can be assembled only by analysis of postmortem observations, not by guesswork, no mailer how educated the quesser."<)  AI Ihe same time that increases In lung cancer have been reported, new techniques and equipment have made it possible lo idenlify more cases wilh cerlainly. Thus statistics can help suggest the incidence at any given lime, but they are of doubUul value in telling us the Incidence of one time compared w/rh another, or whal the real trend is. • Too many conrlicting reports are ignored in Ihe anti-smoking messages from "authorities." For instance, the American Heart Associatlon warns about tobacco but doesn't remind us that in Japan, where the smoking rat is much higher among men than in the U.SI . the heart disease death rate is far Tower. Or that thsl U.S. rate has been fa0ing for the past 15 years In the /ape ol inaeasinp smoking'~_  We are told that more people have begun smoking at younger ages, which suggests lo some that Illnesses associated with smoking should appear sooner. Yel the peak age for lung cancer stays righl around 60 and, if anything, may be mnving to older age- t3  Whlle women the world over have long since joined men In cigarette smoking. the lung cancer rate In men is Inexplicably higher: About a 5 to 1 ratio in the U.S., 2 to I In the Philippines, 16 to 1 in Finland, 15 to 1 in the Nethertands. I 'F Such observalions, needless to say, do not exonerate cigarettes. Yet, drawing conclusions against cigarettes is equally uniustifled. Deceplhe Propaganda _r.n. s wynnr. SnM.,d E~r~~oorm~ m~,a•vr Have you heard these canards? "300,001J peopfe die each year because Ihey smoked." "100,000 doctors have given up smoking." "Smokers have black lungs." Where do these ritually repeated claims come from? Take the "300.000 dealhs" charge. One gov- ernment ofticial said years ago that such an estimate would involve "making so many as- sumplions" that it might be "misleading."LT Yet, a year laler, a former advertising execu- live who Just doesn't like smoking announced that cigarettes cause 125.000 to 300,000 deaths a year. 16 Another government ollieial agreed, claiming smoking was responsible for at least 125,000 premature dealhs a year. He acknowledged getting the ligure from the advertising man, 1'l So the advertising man was asked in a Con- gressionat hearing where he got his estimate. 4 5 ~ OU;"U'7f/7
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Smoking-Health Statistics Slatislics are said lo show that among the 60 million Americans who are smkers, some may fall victim sooner or in greater number than other people to three major types of ailmenls- cancer, diseases of the heart and c+rculalory system, and the pulmonary illnesse.^,s emphysema and chronic bronchitis. These happen lo be our greatest medical problems, coming to the lorelronl as the major infectious diseases of the pasl were'bonquered" through scientilic research. There have been other coincidental trends, amnng ihem the growth in popularity ol cigaretles- 4ientists call these heart and lung problems "degenerative" aifinenls, for they seem to de- velop very slowly, through some kind of distor- tion or breakdown of body mechanisms. Though each illness is very different, all Ihree-and more-are blamed by some sources primarily on one faclor, cigarettes. Laboratory Work We hear about laboratory "proof" that smoki ing causes cancGr. Mice have been painled, hamsters swabbrld'and mis injecled with "lars" condensed from tobacco smoke..Jn laboratories but not found in ~e smoke itsery~ Rabbils have been led nicotine: Dogs have been forced to "smoke" through holes cut in their wirdpipeSS Subsequent "changes" in various cells of these animals have been cited as evidence that cig- arettes cause disease. though production with smoke of human-type lung cancer-or heart disease or emphysema-has never been verified in taboratory experiments. II is no wonder Ihal an American Cancer So- ciety ofticlnl has said that "a clever enough researcher cnn make almost anylhing induce cancer in anlmals, but his findings may have no refevance to human exposure.'(o Somehow it's possible, the argument goes, that direct exposure to tobacco smoke can - damage cells in the respiratory tract. The human heart is not exposed to smoke, and so there is even greater guessing aboul how it might be aftected_ The Problems of Guesswork Simply blaming cigarettes for heart disease doesu t help. In some countries not even sla- lislics fit that notion. The governmenl's National Heart and Lung Institute points out that we've learned so much aboul how to treat heart ail- menls that we overlook how fitl/e we know about their causes. "We tend to obscure our ignorance,° the Inslitute says, "by making it seem Ihal a problem has been solved when it has, in fact, been only ha/f solved."" Emphysema. which makes breathing d8/lcult is a kind of lung damage typically found in older persons. Doctors ponder whether, among other ~ Ihings, it might be caused by inhaling some substance or whether it might result from some blood circulation difficully. In any event, and - despite speculation Ihat smoking has something to do with it. Ihe official view of the government instilule responsible for lung research remains candid: "We do not know the cause ol pul- monary emphysema, how to stop its progress even if detected early, or how to prevent heart disease caused by emphysema." r-l ~ 2 Qp'. ~07ns V.
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is His reply: From the government' The govern- ment man tried to justify it. He took some er- b'rlrary percentages of the annual deaths from various ailments, including several which were not even Claimed by the Surgeon General to he causally related to smokingl 19 Later, the Surgeon General himself undertook to exptain the 300.0P" tigure. He did this by- 1. Taking as his basis the unsupported estimale above. 2. Adding to il another unsupported 102,000 deaths-"from diseases where the reletion- ship to cigarette smoking, while nol so ob- vlous, Is nevertheless clearly indicated" 3. Adding to this enother unsupported but "rea- sonab!e estimate" of 60.000 excess deaths for smoking women, who had not been in- cluded in the earlier estimales.l9 Nobody took the trouble to expose this silty game, or to point out that the "authorities" considered nothing but smoking in comparing Ihe longevity of one group of persons with an- other. But sclentlsls, quietly studying twins, made a significant contribution. Let us see what happens, they reasoned. to people with identical genetics and different smoking habits, What Scientists Found By 1970 there appeared a study of Swedish identicai twin pairs with differing smoking habits, Including cases where one twin didn't smoke at all. There was no association between smok- ing and higher overall morlalit?.oLaler similar findings were reported among Danish twinet0u1 tobacco's foes s1it1 repeal that number. 300.000. A slmpte, rounded, large, impressive-and meani ngless-stat! stic. What about those "100 000 doctors" who have quil smoking? A govnrnmenl bureau coined the slogan, "Maybe they know something you don'1." This is supposed to scare us, too. Well. Ihal figure came from a government- sponsored mail survey of 5,000 doctors. After several fnllows-ups, including phone calls. the survey peopie heard Irom only a third of their sample 5,000 and of those a third said Ihey were ex-smokers. So the government people multi- plied the whole U.S. doclor population (aboul 300.000) by one-third, and claimed 100,000 had quil smoking! 22` The Truth Comes Out Don't biame yourself if you can't follow this. It makes no sense. The "survey'ilself was never published. A disillusioned government agency spokesman recentty confided: "We never did finish it. There were Ioo many errors in it, so many errors that we couldn't do a thing with il. Every time you turned a page there was an errm. .._ It was a wasle or money, but, whal I object to more, it was a waste of Ome.'a.3 No maller. The 100,000 number, so carefully manufactured, no doubt will endure! What about the third canard-the so-called "smoker's lung"? Can a doctor really look at lung tissue and tell whelher it came from a smoker? Nol long ago. a president of the Amer- ican Cancer Soaety lestitied before Congress that this is possible. e't-rt Well, said an expert to the same Congressional commitlee, "I would estimate that of 1.000 pathol- ogisls in this country 998 would say, 'I could not tell; and the other two would say-'I could lell; and that ihose two who could tell either had 6 7 > flOZ 0 7(1R
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Needed: Objective Research It is human naluro In want to assume some things we don'I really know. Certainly that has been the case among many people who have had somelhina to say aboul smoking and health. But that is not the spirit of science. True scienlists make assumplions on/y for the pur- pose of testing them, proving or disproving them. In thal spirit. nolwilhslanding Ihe easy an- swers some people ciaim to have, scientists throughout the world continue lo seek the froth about smoking. Both the U.S. government and the Il S_ tobacco industry are probably the largest sponsors of such research. Over two decades, since the beginning of their joint program, our tobacco companies and grow- ers have committed some $50 mlRion to help independent scientists and research institutions who are seeking the truth. r13 Im many years, their commitment has ex- ceeded the governmenl"s. And there are "no strings: - no industry con- Irol. Every research grantee is encouraged In publish his results in Ihe scientif{c gferature. Since 1954, the Council for Tobacco Research, guided by its Independent and expert Scientific Advisory Board. has awarded about 500 grants and contracts totaling atrnost $30 million to 221 medical schools, hospitals and other research institutions in the U.S. and live other nations.yil In a ten-year program begun in 1964, some $15 million In tobacco industry lunds, adminis- tered by the Education and Research Founda- tion of 1he American Medical Assoclallon, sup- ported 222 smoking and health research prolecls In 87 inslltutions.43 More recently, there have been three addi- tional, major projects sponsored by Ihe induslry. i In 1971. Washington Unlversity, at St. Louis announced a $2 m0fion tobacco industry grant for Ihe study of imrnunalogic factors In cancm.1S In 1972. Harvard Medical School received a $2 8 million tobacco grant for a major investiga- tlon ol pulmonary and cardiovascular diseases.r/u In 1974, the University of Calitornla al Los Angeles was given a $1.7 million industry grant for research on lung defense mechanisms and early delection and treatment of cancer, u* "1 Elusive Answers Throughout these years. answers have been slow in coming, and paradoxically, theories about causes of iliness have broadened as a result of research sponsored by many different sources. Heredity. Stress. Behavior. Air pollution. Viruses. Occupational hazards. Immunology. Things we eat. Things we drlnk. These and more, as well as the hypothesis that tobacco Is at fault, occupy the interesls of inquislt'rve scientists today. As one of the workf's leading scientific jour- nals, Natnre, said in a very recent editorial: ^it is the mark of the successlul scientist that he has rich enough an imagination to look for .., alternative hypotheses, particularly when the conventional one is popular." yµ6 12 13 T dDt7;-'u711
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ertenl lo which our genes may map our actual behavior and choice of Ilfeslyle, ard how these in turn may affect our relative well-being. Researr.h, said a 1974 Congressional r,ommR- fee report, "is making grnat strides with the dis- covery of genetic factors in the predisposition of people to lall victim to certain diseases" Lung cancer and heart disease were among those mentioned. The committee noted that recent research has shown, for example, that some persons produce In their bodies an enzyme whose aclivity Is highly associaled with lung cancer7LOne pathologist has said this could exptain why there are people who "don't do anything Ihal woutd be consid ered conducive to cancer-and yet they develop cancer orlhe lung at age 50. There are others who smnke three packs a day ... and they die at 90 of something else.'3.1 Thn Congressional panel said certain genes have been discovered lo be present in some persons that cause brood disorders leading to heart attacks and may account for a fifth of all attacks in persons under 60.3L Similarly, there's been a recent discovery that some people lack a biological factor which, when presenl, helps protect the tungs frorn emphysema36Whelher this dehciency is more common among smokers isn't yel known. The Nonsmoker Some persons who believe smoking is harmful to the smoker have also jumped to Ihe con duslon that tobacco smoke harms ihn non- smoker. There has been considerable investiga- lion of the goeslion-aM here are some of Ihe re5ults: 10  In California, the Public Ulluties Commission was asked lo ban smoking on buses. Bul alter a bearing the Commission said, "there was no testimonythat the average nonsmoker's hee/fh is impaired by exposure lo the smoke pro- duced by a nearby smoker:' 31  In Washington, D. C.. Ihe Clvll Aeronautics Board was asked to ban smoking on airplanes. Instead, the Board formalized the airlines' ar- rangemenl to seat smokers and nonsmokers separately lor their mutual comfort, citing a US. governmenl study that concluded, "in- halalion of the by-products from tobacco smoke generated as a result of passengers smoking aboard commercial aircrafl does not represenf a significant health hazard to non- smoking passengers."-k.~ IS In England, a medical committee appointed by that country's /eading anti-smoking group, Action on 8moking and Health, concluded in 1973: "There is no evidence that other people's smoke is dangerous to healfhy nonsmoker.s.. _ ." -/ / Scientists have conducted many experiments to measure any effects ol smoke on nonsmokers. They've carefully analyzed the alr of "smoke- lilled rooms," looking lor"pollutants;' under ex- treme conditions rarely if ever found in a normal social situation. They ve shown there is no valid evidence fo justify a claim Ihat the heallh of non- smokers is harmed by smoking of others. 4;Z Yet some persons would like government bodies to adnpt new laws or regulations to curb our right to make our own personaf decisions about smoking. In this case, the solution seems clear: Personal courtesy, thoughtfulness and tolerance by bolh smokers and nonsmokers; a few simple, volun- lary practices in special situalions; and respect for individtral Ireedmm of c,hoice. 11 ' OU;~p'710
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8017SE SKIN CARCISOCENICITY OF SMOKE 365 bfieewererandomlyalloeatedtothethreetroatmentgroul doachtteatmont was applied at three doea levels. Condensate llose level mg./weck Number of mioe/ doselevel Standard cignrette (T4) . 300 150 iS . 16{ . Small cigar (CI) . 100 75 37•S . 144 Cigar tobacco cigarette (C3) . 150 iS 37•3 . 72 A preliminary trial showed that mica coukl not tolerate os high a dose level of cigar smoke condensate as cigarette smoko condcnsote. All mico receiving 225 mg./week of cigar smoke condensate developed severe symptoms of nicotine toritity, aud to in the experiment cigar smoke condensatq CI and C2 were . administered at lower doae levele. Condensate was applied according to four doeing regimea, but in all regimesthe total weekly amount was the same. Repiwue 2 Twice weekly 9~ Alternate dayaincluding weekends 1 33 Monday, Wednesday, Friday 3? Tuesday, Wednesday, Ftiday Applfmtioa of materiale to tAa aCin Condenwtes wen applied by means of a foot operated automatic pipette, delivering a volume of o-3 ml. to an area of dorsal skiu 1•S cm. wide extending from the nape of the neck to the base of the taiL The hair was shaved with electric clippers before the tiest application and subsequently at week(v intervals throughout the expetfineat. Condanaato wu applied for ohe entire •life of the malam Port Otortans agd hi.to-patMtag.p :.Fttll puat mortertt examination was performed on all mirr (except in caaee where autolyeis'wat Ioo ads-anced). which wero found dead ovcrnight. appeared ireecoverebly ill, or tumour bearing animals when the tumoter appeared malignant ~ ged by the apparent attachment of tlw tumour to deeper structures of the Hietological preparntions were exam ined of all skin tumovn, an arw of painted atbb and any other organ which appes.rred macroecopieally abuornul at poet morteta eXamiuatian. If aa.vtis Hodilfatanese were found in emults obtalned with the foucdosing regimes and so all results and final attal.xs were b.,ed on totals for each doee level. The numbers and percentagee of tumour Eeanng animals at 53 weeka and at the completion of the exporimettt ate given us Tables I and II• and the 9nal 5gures of carcinoma bearing animals in Table Ift T00;!0462 ~.~.. ~.-r...~_, ._._ .. ._... _, ~.....,. .,., TIFL 0305360
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E<pe»mentaf inurstigaeions... 31 nn- at in complete as possible, since many experi- ments suggest that incomplete combustion may be an important factor for the car- cinogenicitv of smoke condensatea In both groups maLgnant tumoun developtd, mostly sarcomas at the site of injection (Figure 6) and this octvrred in all stnins of rats in the same way. In mosc cases the tumoun contained residues of the in• jected condensate. A transplantation expe- riment was succesfuL One mruour line has been transplanted now in more than 100 genentions A survey of the results obtaissed with condensate A is given in Figure 7. The percentage of the surviving rau is plotted on the ordinate and on the abscissa the lifetime in number of days. Each cimslar dot corresponds to a rat with a malignant tumour in the experimental group, the triangular dot in the control group. It is outstanding that in the experimental group, treated with smoke condensate, one tutaour comes after the other especially in the end of the experiment As a whole 15 out of the 75 rats developed malignant tuttsouts, corresponding to 20 per cent. Calculated against the 68 rats survivins at the appearance of the first tumour, the yield of malignant tttmoun is 22 per cent as +se \r- .as his to un- r(s_ o- nd at. of or at or a m Ic w { fitarr 6. Laed sproeer in rW of di//nrna BD-Rreiu prederrd mitA ri(amr srno6 eeedrnNan a tAr lirr ef isjrrliae. T011204'74 TIFL 0305372
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26 X. Drua.bay Fi,ryre I. Ineidrnce a/ ne•d.ee eceinunto rn depenLnee on the tntal dma o/ 4-DASr lo. 7 repoate damrer raerinl Irom 03 to 3.4 ma/ki pe d.9. Feed. i.l e•pa.imen4 in BD 11 rNe, continou aeatmens ap to ta- ma.r eppae•anee. Datt raep. erocru: rab uith eertiaomd. Or- dinata: Probitt, Psfeanteees o/ earsinomar. Abtainu S bn.e eknaWd_ Fl•re 7. L(nanr dtprndenq oj the mreinofanfe total dou (Dr) an thc daJj dase`e o) 1-DASt. Fndia` e~penm.nts in BD I! mty cuntinuooi Naatmane. R.aleH 3 stendcrd deviations of the nedi.m eafues a/ the total dmet Ordtnata: total dotss adminirtoad up to tumose aphonaee in 60 Per cent o/ rab. Abuiu.: daily dosape in mr)ks 6oIJ ueiaJM" hardly deteetabie in the diet of the rats by chemical means. Since the induction time in this dosage gtoup wm 900 days and is thetefota of the same crdeea the ma,dmnm lifespaa of rats, we can cna- dude deGnitedyrehat the effeca of afl succeniw dases, even the sma0etr reeains completeky iaevenble over the whele lifeipan, aed thee effe:ob sum up uedl fina0y the manifceadon of a esrcinoma oceua The medium value for the torol das (Dso) and the induction times (t,5o) eb- served in the different donge gtoupe ate sunnnatimd in Table 2. They shmw that with the highest daily dosage of 3.4 mg/hg the antal doee for the production of rancer in 50 pa eme of the rats was fiS0 mg/kg against only 90 mg/kg with the smallest dosage of 0.1 mg/day, the difference being nearly tenfold. daJ7 dony mL/k( indaaeYn tuna deN total doafa i..r/kl 3.4 250 852 2.0 342 685 1.0 407 407 0.5 560 290 02H 607 170 0.2 675 135 0.1 900 90 7.61. 2. Dwnaapansa rdaennehips 6s /ht psa. dueNo. a/ anwduel creinomm 671-DASS. Pead• inl rrrerimme in BD l! eaa. T 004!0469 TIFL 0305367
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MOVSS SKIN CARCISOOE\ICITY OF 3sfOKB 367 increaw in the incidence of spontaneous adenoma of the lung or malignant lymphouta. DISCL'SaIOA Results obtained from these experiments are cnnsidont with the work of- Homburger cl al. (106:4) who found no aigniticant difference in carrinot-Mnicitv to mouse skin between .smnko rondensates prepan•d from cigarcth:ti made of cigar tobacco aud th~ made from U.S, h•)m <ignrette tobncco. "I'hcv are in aontrant to the Sndings of F;tsnev (1Da7) who reported that when the back.o of mice were painted with condensate front the smoke of cigarcltes m:.de from duo-cured and cigar tobacco ren(>rctivclr, the latter gave rise to pnpillmnnttt in u0i; of the surti- vare in contrast to sm tuntours with the lluc-cured contlcusnte- Croningcr et nL (193a) com)wtrd the earrinn/lonicity nf cignr smoke condenNitq both nicotine free aud containing nicotiuo in Swixs and (:Apt stralllSnl Ittice. They showed a statistically xignificunt difference between rigar and cigarette smoke eondensates in papillonta production after 12 months applic:uiun but oatlv a borderline signiflcauce nfter Is months. They concluded that to establish the relative carcinogenic activity of these tars further. additional studies with a larger number of animals would be rvquired. Kettsler (19U'2) in a simflxr comparative etudy sttuwed that the incidence of papillomas produeod by cigar smuke condensate was no different from that of cigarette smoke condcosntc. Homburger et al. ( IOG3) suggestcd that differences in carcinogeniltity between various tobacco stnokecuudenaates in various reported studies• may have been due to differences in combustion. pyrolysis or skin application, rather than to the nature of the tobacco. In the present series of experiments a number of these possibilities have been eliminatetl by the use of standard methods of condensate production. skin n),pliratinn. and che uso of tbc same tubucco fur the manufartute of the cigan and the cienr tobacco cignrcttes. The differmnce in carciuogenieity between the condensates appears to be due to some factors connected with the physical differences between a cigar and a cigarette, e.g. the difference between gnnulated and shredded tobacco, rather than to the nature of the tobacco. An interesting finding in these experiments hae been that in life time painting with the three condensates, providing tho weekly total umount of condensate applied is constant, similar tumour yields nre obtnined by twice weekly, three timee weekly, or alternate day apl,iieations. All the major epidomiological studies of cardnoma of the bronchus in the United Kingdom and North America have shown a much lower incidence for cigar smokers compared to cigarette smokers, although a higher risk titan for non~moketa (Doll and Hill, 1964; Lombard. 1905; Hammond. 1966. Kahn, 1966). This appears to be in complete contradiction to the evidence from these experi menta. Homburgereta[. (1SW3)statedthatthamouseskinbeantlitttetesem tanc to the human lung and while it tomains a valuable tool forthe study of cnrcinogerte- aia, data derived from it are not directly applicable to the evaluation of the significance of results obtained by clinical statistics. This may be the simple aaswer, but there is however, evidence which suggests that other factonr could account for the discrepancy. One theory of carcinogenesis postulates the direct interaction of a carcinogen and a t.uget organ. The presumed carcinngen for . human smokers is in whole tobacco smuke, while in motne skin experimenta it is T0o4"0464 TIFL 0305362
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J6g R: F. DAVIES AND T. D. DAY in the condensate. The target orgon in the mouse is epidermis and in the human smoker the brondtial epuhelium. In the exlxrimentil proccdure ne ensure thaa tho two interact by directly applying condensate to the epidermis. In man the interaction requima the nctive inhalation of the smoke taken into the mouth. A eurves of the uthaliug habits of mule smokers in the United Kingdom (T'odd. 1965) showcd a higher pcreeutaga of inlmlen among cigarette smokers thaw among cigar smokera, a differcnce which may possibly account for the epidemiologied data. .16 the present time smokers are being advued to change from cigarettes to cigan. Any asaessment of thc relevanee which our experimental results may have to this aSdce. the responsibility for w'hich resta with members of the medical profeasion. oupht to take into account a number of factors. e.g. the extent to which meuse skin painting results can be estmlwtated to man; the importance of amoke inhalation: aud the extent to which the inhaling cigarette smoker alten hls smoking behaviour when changing to small cigan. Much mote information about the iuhaling habits of smokers of cigarettes and amaLL cigars is utgently needed to permit a comudered )udgment of this problem. . atiMNASt The carcinogenicity of smoke cordensates to mouse skin prepared from plain cigarettea, small cigars and cigarettes manufactured fmm cigar tobacco hee beeq compared. A staciaticallY significnnt increase in mouee skin eareinogenicity has been shown with cigar smoke condensate compnred with smoka condensate from either flue-cured or c enar tobacco cigarettes. There was no signigeanb difference in mou.q skin carcinogenicitp betweep smoke condensate from cigarettes tnade of flce-cuted tobaeco or cigar tobacco. Thcro waS no difference in incidence of spnataneoua oocurYing tumoursofother organs folluwing applieation of any of the thn.a eondensate. , We thank alr. P. \. Lee for the statistical assistance attd Dr. J. IS. Whitehead for providing the apeeimetn of condensate and their analyee.. REFF.RE.\CF8 Giw:rmuw, A. 8.. Uu.uuM. & A. Avo WYxata, E. L.-(1988) CeearrRei..18,1263. ~ DaY. T. D,l1nG) Br. J. Connr, 71, 5& , Dota. R. eVn Hu.c. A. H.-(IU6i) 8r. mef. J.. 1, 1389. F.Lretttotuvq H.-IIfM1R) /kitr. TnGtl•Jorark. 3, 101. -H.vxoxn, E. C.-{ I Olie) \'rdw. Cnartr I nM. ]lonegr., 19,127. Hoaarxnxe. F.. Taan;a. A. a~o V.tnan. J. R. (I:IO3) J. n•de. Cancer 1M., 31, 1446. IGns, 11..1-J11u4q \'ntn. Concrr lnel. Anuogr., 19, 1. IsxstsnC.J.-{101L'')'Tulueeoomllicakb'. Spring6ukl,Illinola(CBadnC.'3ltomaa) p.t5. La:xex)_ A. lf. ..a H.txaet.L. 'r. e-1MM) ,leufyt. Cherx, 30, itl0o. LoMaASD. H. 4-(IUWiI Cmaer. Y.Y, 19. 11t/1. pAsaxx. lt. I1.--{Itnlt) In;' Rcvicw fi':•ctivitira 1963JiN'. London tTub.eeo RcxerCh Cwmeil) p• :15. Tone.ft.p.-Itut16l'~latiaticnnl'SimrkincintheCaNedlCingdan',f4edon. Tobacco R~reh (fauncil, ltrrarch 1'nl•* So. I. Ww;r.t. C. U.. Sw',u%, 31. I.. ..Nn CoweLLY. J..1.-{11kiU) .lanlyt. CRr/a., 27, 630. T0020465 TIFL 0305363
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32 H. Druc.F,ey 0 iee tia in .m in in raa an xa ias ~w rw Fisxre 7. Appsarence of malianaet rumo.rs and death rats of .ats injeatd with tedaeeo rmeke soa- dmtatt A(thtek line) in aomperiwn t0 that o/ eontrol raa injeaed with the safoant (thin lina). Cirsular dolr: malignant Iamo.n of tha aaDtiTantal rct! (75). Triuda/ar dot: malifnant tamotar of tka sontrnl els (75). OrdinaL: Persantade of ra®ioiaf rcb. A6reiosr daF of twwad tinu. against only one single tumour in the cea- ttol group, an abdominal sarcoma. With condenrate B 13 malignant tumoun have been observed nearly all of them rarcoma at the site of the injections (Figure 8). The causative role of the smoke wo- detvata in these experimente is indiuted by the following faeb: te y 1. the tumour production of about 20 per cent in the experimental groups . 2. the local development of tumoun at the site of the injectioro 3. the accutuulatioa of tumour develop• ment at the end of the experiment 4. most of the tnmoun developed more FiPre 8. APPeoere of mali,tnant tamo.rs awd d.ath rate of set+, iyrsf.d aritk ro8aeso nnuke se.- detuatr B(tktck tlv) in aompantan to that of sontrot rea injeeted adth ehr Pa.r tolwet (thim liae). Cisalar defc mdla.mt tweowr of the eeparimannlat .asr (76). Tnaa fulo dou mdirnqt , torwaar a/ the soebat rnu (7J). Ordi.eJe: Parunteee of nraioinl rats Aouurar da7+ of .u.eitd time. Toatioq7s TIFL 0305373
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/ mr-daa +rndrnve ne -OdSt )or 7 e..rlns frm. o~. F..d- RD ff rau, vp to eu. I Dntt retp. .«noma. Or. v/. a: S Wn.J rIN smallest ~rcnce being D. in 1ke pro- rD.iSt. Fe.d- Erprrimento! inurrtigationt... Plotting the results of table 2 on log log coondinates yielded a strikingly linear rela. tionship between the cazcinogenic total dose and the daily dosage. (Figure 2.) The fint conclusion from this is, that the production ot cancer showa a clear and surprisingly simple dox.reponse relation- ship and does not need any metaphysical assumptions. On the other hand the results show that tutnoun can be produced by con. tinous eapostue, e.en with such a very small dosage as 0.1 mg/kg per day, but this only after a very long induction time of 900 days. Since the rats at the begin. ning of exposure were already 100 days old, the tumuuo developed at an age of f000 daa, which is the maximum of life. span of nts Thetcfore the use of smaller dosages was not feasible because the in- duction time would then become longer, uader such dxurmtsnea, than the life- span. The linear relationship in figure 2 shows condusively that an extrapolation to threshold dosages, which can be con- sideted as "safe" on continuous exposure is not possible. All my ettdeavottn to find 27 an indication of such a safe dose with carcinogens have been fntideas. The im- possibility of giving a fair estimate for any safe dose with carcinogenic substance is a very serious problem. On the basis of our experimental results the limiting fao tor in the production of cancer is appa. rently the limited lifnpan. For such reasons the t.ay in which the normal death rate may interfere with the production of nncer must be investigated. Such an interference naturally has to be respected the longer the induction time becomes in the case of small doses of po. tent carcinogens or of chronic exposure to weak carcinogens. These possibilitiea ue demottsmted sehematically in Figure 3, which is based on experimental results with i-DA8 carcinogenesis in rats. In this figure the variatfon of the percentage of tutrsour appearance with induction time, or age of the animals, is given by a number of sigmoid curves, each representing the action of a certain dosage. The curve for the notmal death rate goes invetsely with age fresm 100 per teae down m rero. Fi- aA r YA t r f . -I I ~ t I N4 ~ I i I t! i u! I I ~ I I I I Fiena 4_ Srk.wa fo, the inee.r, of eaarn in.idearr mith Jratonaetiwt of tAe Gfapa Fpn 3. Tka depe.deaa" uj thr I.waek of the iad.ala. Nn.e ewd of tAe i.mew )i.dd Pon rkr dotan far tesen dosye arVYN t(hin rarats/ aad the istnf.r(nee of the no.w.f d.uA rata Ithiak ear>el- Ordinm.: Po- Mnaae of tYmoYra rlJf. Vf JYI. muarr. A6rsitn: time (H. Lnakrq, Arta Uaio ieternet. C.aa.r 10. 39, (19!{). TIFL 0305368 f
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3 Experimental Investigations on the possible Carcinogenic effects of Tobacco Smoking Professor Dr. EL Druckrey, Freiburg, Crtrmatry The possible cancer risk of tobacco smoking is a serious problem, not only to the medical profession and to scientific research but also to the manufactureo of tobacco producn. At the same time it is certainly a vety difficult and complicated problem, which in my opinion needs a vere close cooperation between scientists in different fieldt, as well as between health authorities and tobacco tnaoutae- tutea of all interested couetries. As a result of my eaperience in timilar fields I am con%inced that real progress will atise only by such coopention with genuine mutual confidenea Being an optimist I think that, in principle, the technical pro. bieuu can be eventually tolved. At the preent'iime howevet the povibk risk of tobacco smoking should be conaideted purely as a.ciendGe pmblem. That means, it should be invatigattd witheut any pts- judicq without any bias, and cumpletely uninfluenced by comtttetdal viewpointt. If the ptobiem is ditcusted in such a way, and in full confidmre between meaeeh workets asd indtutrial invmdgaton, dtee I think a tympodum lihe this may be very helpful for futwe development. I vrry much apptecate the fact thit the Swediah Tobacco Monopofy, oorganized this sympo- s9um and I am very happy m participate in it. When considering the po:u3le cancer risk of tobace.o uooking we have to deal in the main with two gtoups of pcoblemsc 1) the chemistry and physical ehemisety of the suspected materials and the ptoeea. sa involved 2) the medical aapectr, espo- cially pharnueobgy and pathology. Being a phatenamlogist I want te restrict myuJf to my own field. As far we ean say at the moment, the meCltanltm of CarCnngtaSla is in some respects different from what we know of the tnechanimt of other drugs. Many ape. ciaf problems ata involved which must be in.atigated thotoughly. In order to form a proper pharmaeobgical attessment the first question would wocan the natuta of the active su6stenee or substances and the specificity of its posible catcioogeaio action; the second would conrern the na- tnte of the dosenteapome relationship. This includes the problem of the efficacy of small doses and the eairtence of a thresd hold dose, which can be considered as "tate". Ite final problem is that of the scvenibility or itterenibiliry of catcinose- nie effeas and the time factor involved. It is the wiyat wmae in phamucology to statt an inretdgation with quantitative aspeeo in mind, so as to lay a ptoper basis. Sinee such quaatineve experiments ate .ery difficult with tobacco produea and 'r 00'.'.046"1 I PA -000467 - TIFL 0305365
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28 H. Druckrsy gure 3 shows, that the tumour yield is nearly constont at 100 per cent up to snedium age and only the length of the induction time increasea with decreasing doszge. But the more the normal death rate interferes, the more the percentage of tumoun decseases until finally it be- comes zero, apparently because the ex- pected induction time becomes longer than the maximum lifespan. Strikingly similar results have been observed by H. F. Blum (6) in the production of cancer by ultn• violet light. from this it follows that when dealing with weak cardnogem or small dosages each increase af the lifespan should prv duce a corresponding increase in the fre- quenry of cancer. Figure 4 shows schema- tinlly how a prolongation of the lifeapan would leadso a higher frequency of can- cer for two different cwnditiom •(from point A to B or point C to D). This eor• responds very clearly to practical e<peei• ence with hsutun cancer. To invat'sgate this expeeimentally we tried systematically to pmlonge the life& span of our rats by increased care. It was pom'6k to reach a medium life span (50 per cent sutvivon) of 930 days against 550 days in former ynn. Only under these conditiom could the cardrsogenic action of stnaB dosages, such as 0.1 mg 4-DASa, be desntsnnnted cleatly, which wae not feasible before. From rtvs the great im- portance of the time factor in czdntr genesis can be clearly seea In this rnpeer the posasble risk of diY condnued eaposwe to a carcinogen is of special inteseat and this was also investi- gated eapetimmtally. Itata of our BD TII inbredd saain have been treated with 4-DAB in the dieq the daily dosage being a comtant S mg per rat. After admtn+°A- thm of a ptedeeersnitted total dose, rang ing from 1000 down to 200 mg the tteat• ment was stopped but the obeervadon of the rats continued until normal dnth. The results of these experiments were as follows. The smaller the total dose was, the longer was the induction time but on the other hand the tumour yield decreased considerably from 81 per cent in the group with the higheu dosage of 1 000 mg per rat to only 20 per cent with 200 mg. On plotting the percentagen of tumour yield on a prabit scale against the total dose administered using a log dose abs. cisea a linrar relationship cesulted (Figure 5) corresponding to the observations Fif.rr 5. Lndms. rf fiwr enter it rur u dw y.ndsnt on the solal dorr of 4-DA8 ednrinlrte.ed 3F di,emuinud e.eposrre. Ths trretmed ws fa- knupbd a/fer . totrl dan ef 700; 300, 300, 700 ad 1000 snl 4.DAB rsrpssqwaF. mentioned before (Figute 1). 1lserefore an exteapolatias to the parble risk of smaller doses is valid. This of musm can only be calculated in tetms of prob• ability, in line with pharmacologica! T 0020471 TSFL 0305369
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c, HzsA!, ia. fG,i papa is nGo puWtihed us a rt.ppbmmt to ua/uae .7n/rq6r oj ACTA MEDICA SCANDINAVICA Symposium on Chemical and Biological Problems Related to Smoking Stockholm, May 2-g, t g6o The Medial Advisory Council of the Swedish Tobacco Monopoly and The Tobacco Research Committee of the Swedish Medirsl Research Council STOCKHOLM tg6t roU~. .o486 TIFL 0305384
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386 A. F. DAVIES AND T. D. DAY Tsnts I. Tumow Bearing Aninutla aJkr 5'2 utiekw CondwuNA 300 mg. 1S0 mg. TS m;. 37-5 mg. TI rtend.W cig.nt4 (H{mie./pooPl . . l7lil•B!rel . 16(i1.1%) . 2(1•4%1 . - Cl aig.r (Ua mice/pauuP) . •- . ?2 (iS•3!:) . 6441S) . 1 (0•1%) C3 eigv tob.e<o eipnte. a(6.3 ie) . 0(0'0efe) . 0(0' 0%) TABLE II. Tumoar Rearing Aninwla aftar 116 utieke ConMrt. 300 mg. ISO mg. IS mg. 37•5 o+g. T4 rt4ndvd eiEe.wue . 49 (31•0 a) - 30(^7-eq6) . 11 (S-d a) . - Cl eigv 64 (44~4%t . 30 (SO'a%) • 9l6'r%) CRCigvtobeacungartne 23(31-9%) - 4(5•6 a) ?(2-6%) TAnt.z III.--Carrinoma Bearing Animnla after 116 useks Cond.n..b 300.4. 130 mg. 73 ar1. 3"I -5 mg. Ti41MHdciEWNw . 3f(:0•1?y) . l9(132%) . 1(0•7t/) . - CI<ig.e . . • . 1 • 39127'1%) . 1011I•1%) . 3l3'1%) C_eigvtob.eto cigrMOe . - . 1002.0%) . O(0•0%d . 0(0P0%) One problem trhen comparing the careinogenicity of different materials is that of differing mortalit.• rates bet..een trmtmenta and several metlwda of gtandatdige- tion for incrsased mortality have been attempted. The mortalitr ratca for thia azperiment are given in Table IS' and it can be scen that theta is little difference betwcen Uro mortality rates. age stnndardiaation for mortality rates wag applied, but, aa expected made no difference to the final analyses. T.ntt IV.-.Vortality Rata Numbrr .nd I~,eentege of mieft d..d Tsw~ Initil nunhw ef miq 52 wwb 72 rveea. y 91 Y'ceW 116 T4300mg. . IM . 67(31•4%) 91 (g3.Y$) 133/02-4%) 114(100%.) T41S0ny.. 1" . 37("a•7o) 67(W•{%) 134/93'1$0) IN/IW%) T471mg. . 144 . 33(21•9%) 74I17. 4°~) lle(02•690) IM(100%,) CI130aq. . iM .=9(20•1 p) 93(17•gq'r) 131(91%) 1N(1U0y,) C175mp . lN . 30(70•g?;) 6aN5-0?e) 107(7i•39e) 11t1100y~) C137•5mg.. 144 . 33(2t'=:) 6a(47-9?I) It6(e0~6a) 1441100%) C2160,.g.. 71 . la(r1-0!'y) 3$(4a'e%4) 57(76-E?$) 72(100%) CP7gme. . 72 .. 1@(I6.7"e) 36(50•09J 63(661!') 721100%) C937-Smg.. 72 . IO(13-9 a) 33(43'a?'e) 63(94'4 0) 12(l00%Q _ From the results in Tables I. II and III it appears that the conden3atw from small cignrl is more carcinogonie to mouse skin than that from either standard eigarettosurcigarctteamndefromcigartobneco. Anoutalyxiaofvarianeeconfirmed th6ligniBraneo of thc9c results at the P< 9•46leveL The results alao ehow that there tino significantdifference in the mrcinogenici6y to mouse akin of condensate from cigarettes made from flue•cured tobacco and from eiyattettee made from cignr tobacco. The incidence of other tumuouts in the mice wna similar in the three treatments and did not differ from that found in 13'B) untreated control :mimlda from another experiment housed uudor identicaL conditiotw. In )ptrticuiar thore was no Too~0QS3 TIFL 0305361
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11•ntoked to- nt alcoholic r ci~ uecta, d~e afco- Lnll'etion at ihis proce- :J.,ut 200 g !.,t iocuhip: f. 20 to 100 ..rra ~moke ,mnt of the .,,rrage. No a pmctical ihc csttact rqual patts doolml to a . nt. Control .laswellas ~rrol inject• .%.rd no Gai- '-.tract waS iion in the -"uwing the u~cd in the . 'akc conden- r rvfctrod to -rtions wee timc of 465 per rat, iihcformer ~atct. Then d with to- '.11 injection :'cing for a 'vr content '• recovered :.,,t depress- about 800 -t reduced ~ rats. Four '..Ing Of the '1rr of rata .r thcro sar. 1 (•'.xprrlmentaf in4llfiaationl ... ---•r- - ~ 4` 7r-1 y 37 Filttrt 9. Lataf rarecmas in raU pndated a tke rite of inlesriont with a 70 per tnt elmAolfe .bed of mumoked tobaeta. comas at the site of the injections (Figure 9). The experiment is not yet Fini.hed. Up to the praent moment 18 rats have showed malignant ttsmouti. 49 died with- out tumour and 18 rats are still living, some of them with developing tttmoun (Figure 10). Therefore the tumour yield is in the order of 22 per cent against 20 per cent in the experiments with smoke condettsates. This striking carcinogenic effect of tobacco extract is more surprising since the total dose administered, 3.2 g . s. ------------- J ~ so m n «.. r:.a:.. - e a. sno ze a sw wa sn .u. rm ww .n Firurr 10. A,pment* of ma6rnant tumoart a,td d.ma reb of 7J rat, in/rrtrd with a 70 pn eent aleoholie .xtraeJ of anouoked eiparab tobaeto (not yet )iaisard). Blaek dob: malif"at tuna..e Opan efm4r. 1.naiae tamoan. 7ooL>oq5o TIFL 0305378
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f $93 ~ A STUI)1 QF TIIR C.U?II'.l1t.ITl%'I: CARC'I\Ut:1sSI('ITl- OF CIGARETTli AND C1t:Ak 3Mu[Ui C'USllL•'\5:1'1'4: US SIUC~SG bliIY R. Y. DAVIEY lsu T. D. DAY Front the Tal.xev RaMrrh (:'ur,<ii LaGoratwin, llarmgai Rea11Yd M publkettcn kYluuvy 7, 19aD A Yaeveol3 puhlicatior. &unt tiusa ).aborntnriei (Da.r. 1957) reported the carenoganic action to nmou:r• nkin of ri¢urcltc smokc eonJ~are.atc altpliai cithcr aa ?i hour condetunte. stordl coudvmute or the ncutrui frnetion tn,nt .tortd aindc•n. uato. The work now relwut.•d ia a cnnrywriwn uf the rtroci6c rnmt~ =kVn carcinogenitity of ~muks rundem,ur» prrl.,nd from small ~i;ntx, vfeart•tres manufactured from cigar tobacco, and cigutcttes tnwwfaetured from (iue-cured tobaeco. Ptavious stutlie+ rnlwrted by other trurkcrs tC'rouiqt•r rt al.. 19:,a. 6etmler. 1999, Hombutger a at., 1943( u.ing tvbeaeu pruducta rommerctallc ncai,abk in the Lruited Statca at thet time. have xu~PP.ted n greater carcinugenie activity of snnoka crondeneatc (runt ci¢nn1 lhan smoku rundeneato front ritqrcttCt nmuu- ~faetured from blend, conlaining both air mld ttue-curud toba<en. but atatistieahy signifieaut differences have not been obtained. >t szaaau ..a u )t cittn oa Ciqare (Ct) Small eigatw (length 83 mtu.. circumktt~tscn 33•7 nun_ average uei¢ht 1.89 g.) wers speciallY rnanufactured frorn a com(w.ate blrnd of chtnr tobattv relucamtting emAU cigar bmnrls smnktd in tttv Cnited h:inudom. 77tc tillrr was eranulated tobacco and the unyqer nnd hindcr nntutrnl Lenf. (Cinrs.ceec t.rapprd indivi- dttally in trllophane and packal in b:uch.* of Brt• in cartlbuurd aatmis which urrn aleo trrappcd in cellophaue atd atoted at ".t' C. and commikd hnmidit}• of G9ie RH. before uee. Cigardha (cipur tobncrn) (C'~ ) - . C4ganttw (lenReh 71) mm., cirttmf<n-nce '.i-t mm.. avernge urigltt n-ol g-) nete apeciagv tnanufucturt+t front ehe ~me toltucro w uwtJ for the risan drscrilxd abo\•a but ln,stead of bPing Ml,tllattd. the lotvle'eo \eYa Shre/}t(ed aL 54/ :/tta per inch atd wrapped in normal ci2aratto yapa•r. They a•ere lutcked in batches of . 50 'ut t•aeuum•aealyd titu and etoenl at 1' C. before uee. CoMrol r(gardrra (Ttl Plain oigarettes (length 4o mm.. circumforenee 3a•S mm.. pvetnge xeiqhb 1•99 g.) were apeckdl,c mmtufuctuted (rotn a comprwite bknd of Nuc•euted tobacao represettting the major plain cigntctte bmuda xmokOd in tito UuitKl AhtgdOm, packed in butches of 3u iu vncuum-rcaled tius and stored at i' C. bofwe uae. C1/ PA -000465 •7-G02U460 TIFL 0305358
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IC ncer J in utty ,<es• ospe. Being r.Izelf i, the scme >w of Y spe- utbe form the < of the cnic ina- / of uss Ia Ihe oge• d. t°gy itive xsb. are and t s r Esperimentaf inontigatioer... have not been feasible until now, I want to mention a few quantitative experimenes we made with other carcinogenic substan. ces in order to provide a definite basis for the discussion here about the rype of risk which may be involved with tobacco smoking. Our first quantitative experimenta (1) were carried out with 4-dimethylamino- azobenzene (4-DAB, "butter yellow"). This substance produces liver cancer in feeding experiments with rats aftes ehso- nie exposure. The results of these quand- tative teats are summarized in Table 1. a daify doraae nt( r 7.,d.ctiue t:m~ dap D totai d>n nsa 30 34 1020 20 52 1040 10 95 950 5 190 950 3 350 1050 1 700 700 Znble 1. Dorean)ens. rstederuAiP{ ie Me Dro- dYLttGs of eePatEn1Y bl e-DdB. P.ed'era rn Onimeate iw 9D Ill retr, euvYrtvout er~afraent. They show appruximately an inverx pro- portiottaGty between the length of the in- ductioa time and the daily dosage. TLe total dote adttdnitteeed unal the appe+- rence of the mmour is near)y the taree in all groups and is not inereased by fneaio- nadon. From tho it follows that the pro- duction of the liver rmcer is a funaion of the mtal dote, evm if its administration inclrtdet the whole life spaa This tnearr, that the effece of all successive daaa re* r/tairl eotnpletdy ir[eVCrsihlle oveT the whole life span and integnte with time. Thetefore we proposed for this new type of pharmacological acdon the term "sum- mation aetion^. It is defined as a function of the sum of all sucowive dom (2). According to phamtacologieal eaperien- ce the rtsE of a poison by chronic exposuse 25 depends upon the reversbility of the ef. feces (3). The lesser and slower the reven. sibility is, the more the effeets accumtilatt up to a summative effect. Since the effeet; of csrcinogaa, as will be demoeetrated later, are apparently hmn;,ersible, such substattces must be cotnidesed as especially dangerous. The reproducibility of the ressdu ob- senrod in the eaperittxnts with 4-DAB had to be tested with other aecinogens pro• ducing other types of cancer. We used the 4.dimethylamitto•stilben (4-DASt) which, according to Haddow, Hartis, Kost and Roe (4) produces earduct arcinomaa by oral adtrdniuntion in raa The quantita- tive experiments have been performed with my coworkers D. Schttrihl and W. Dischler in a similar way as before with 4-DAB. Seven dosage groups were used with contnnt daily doaagn of 4-DASy narnoly 3.4; 2.1; 0.5; 0.28; 0.2 and 0.1 mgJkg body weight. This tteatmmt wea continued until the ftnt appearance of a tumour. I3e total dose adaoisistesed up to this time was then noted for each rat The point is that, if the catdnagettie sc- tion is really a function of the sum of all successive doses, i.e. of the total dtee, thm a clear relationship belMlm tnIDtwr appearance and the total dtue snuu be WTecte& The results were as follows. On plotting the appeuarsee of ear)s malignant tusttoer on a probit grid which has the peremtage of carcinomas on the ordinate and the log of the total dose on the abseras a raeer liomr relationship in all diffemst dasage groups was obtained as is shown in Figtre 1 (5). This fsgure demonstnts ahcady that the total dose neoasary, for ptodocing carcinomas in the different groups is ssnailer the lower the daily dosages shat have heee used, and this holds down to the very amall dossge of 0.1 mg)kg per day. This dosage is so small, that it is 7-uo2046s TIFL 0305366
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364 A F. DAViE3 AND t. D. DAY Smoting proudure The automatic arnoking machine described by Day (1D67) wu used for smoking all these products, a separate smoking disc furnished with appropriately sizad boldere being fitted for cigar smoking. The sama aturdard smoking patumeten were used with respe<t to puff •roluate (?5 mi.). puff duration (-' seconds) and puff interval (I minute). The cigarettea were smoked to a 9o mm. butt langth and the cigars to ."_3 mm. butt length. The average number of puffs required to produce these butt lengtba were: (a) cigars 19•9, (b) cigar tobacco cigarettes 6•a, (c) conttd cigadttes 10•9. II'Aole emats wrdenmte ( IYSL') Cigarette smoke was collectM in a glass trap of similar dimensions and construction to that deseribed by Elmenhorst (101io) edoled in ncetone/crushed aolid cnrbon dioxide. It has been found thnt provided the bottont end of the central exit tube of the trap is within : mm. of the bnee of the jacket and the well of the tntp is filled with glear helices (4 mm. dinm.). the metal sleeve nead by ELmenttaryt is not rrquimL On completion of smoking, the trap wns allowed to attain room temtnrature. condonard smake was wnshtd from the trap with acetone (about 700 ml.). the wasltings tiltened t)tmuyh ghut wool and nn uliquet taken to eheek twn•valncik whole smoke yicld bc determination of nicotino by tbe method of U'illits. Swniu and Conne6y (lbnu) si modified by Laurene and Harrell (I9L8). \'on•svlatils u•hole emoke condeneote (.VVIYSO) Solvent nv removed from the acotoue sulutian of WSC in n weighed Aaak, using a rotar,r evaporator on a water bath kept at ao° C. with a water auction pump at a vacuum of about 2 em. of mercury. evaporation was continued untiL the non•colatile re.siduo attained rotutant weight. The average yields were: pq . 'i¢:m. :17am,.cigcr. r,tn0t• ~4T413my!;viu;tr, (b) eigart•tten made of cigar tobawv. 1a•i nsg./cigarette. raoue 1'0•:.-_i-7 nsg..cignrette. (e) eentrol cigarette, 20-3 ntg./ci{rarctte. cunga 9i4~_tl-i mg./cigarette. All doses of all materials applied to animals were extxcsrd in tcrms of the weight of \PWSC delcrtnined in thia way, each individual desc, irrespective of weight, being delive:ed in the ateandard volume (t/•3 ml.) of solutfon. Slond ecadaneafa XVAS(: collected over 4 weeks was combind. stored at -^_9' C. for a further 4 wxeke, discnlced with conatant stirring in ntutone/u•ater (9 : 1, z-/v) and the solution dilutad to the appropriate volume uitla the same solvent prior to skin applicaWn. dfiee Fetttab, albino mice of a specifie pathogett•free strain were obtained from the Pltarmaceuticala Divieion, Imperiul Chemical lndustrien Ltd.: at 4-e weeks of aga. )fin were housed three in a boa. in stcriliscd galvanieel iron boxes containing afcri(iecd sawdust. Mice in each box n•ere identifitd by ear punchuta. They wae fed paateuriwetl Osoid Lreoling Diet pellets and provided with drinking water in etarilix+l bcttles ad libilun.. r002046j TZF'L 0305359
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36 H. Druckrcy tion of similar effects an subcutaneotn tissue, especially in rats. Since moreover in this species only I per cent of the observed carcinogenicity of smoke condettutes can be attributed to the benzpyrrne content, it seems reasonable to look for other carcino_gem rather than tn discuss the possibiflty that 99 per cent of the aa tion should be due to cocarcinogens. For such aasumptions no sound scientific back• grotmd exises, which it is indispensable to have. On the other hand the carcinogeni- city of tobacco smoke condensates is now established beyrotmd any reasonable doubt experimentally in mice as well as in rabbits and rats, it seems imperative therefore to look for other carcinogens without any bias. The first problem to be considered is whether or not carcinogenic substantts are preexistent in nonsmoked tobacco. With tobacco extracts prepared with methanol and aftenvatds with methylene chloride E. SM'vnder and G. Wright (11) obtained papillomas and carcinomas in mice using the skin painting technique. The tumour yield, however, was considerably lower than with smoke condensates. This may be due to the solvent used. On the other hand there exist sotne statistinl indications for a causatfve role of genttine tobaoco in human cancers. V, R. Khanolkar and co- workers (13) reptsrted, that taaeer of the mouth cavity, the incidence of which is outstandingly high in India, representing about 50 per east of all cancers in men, is observed mainly in people who chew tobacco. Therefore the possible prtsence of carcittogenic substances in tobacco leaves was disnased. Furthermose R. L. Cooper and j. M. Campbell (14) directed attontion to the high frequency of cancer in the nasal and sinus cavities in Santu negroes who have the habit of taking to- bacco snuff but smoke cigarettes only to a small extent. These experiments gave fur- ther impetus to investigate nonsmoked to- bacco for carcinogenic activity. For this purpose 70 per cent alcoholic extracts of tobacco, as wed for cigarettes, were prepared. Alter estmction the alco- hol was removed by vacuum distillation at low temperature. Employing this ptvice- dure 1 kg of tobacco yielded about 200 g of extract. Therefore the relationship: "extract to original tobaccd' is 20 to 100 against the 2 to 100 for tobacco smoke condensate. The nicotine content of the extract was 1,5 per cent on the average. No benrpyrene was detectabla For prdctiol application in rat experimenn the e:azaet was diluted with a miature of equal paru of glycerol and 70 per cent alcohol to a final concentratioe of 33 per cent. Control experiments with pure glycerol as well as with distillation rrsidues of glycerol inject- ed subcutaneously in rats showed no car- cinogenic activity. This solution of tobacco extract was tued for subcutaneous injection in the same strains of rats and following the same dosage schedule as was used in the former experiments with smoke conden- sates, each dose being 57 mg referted to the original extract. The injections weee continued once per week for a time of 465 days up to a total dose of 32 g per ru, the same aatountas was used in the former experiments with smoke condenuta Then the injeations were stopped. The number of nts injected with too- bacco extract was 75. After each injecdon the rats showed convulsions lasting for a few roinutes, due to the nicotine content of the extract. But the animals recovered very quickly. The vitality was not deptes. ed, the medium lifespan was about 800 days and therefore certainly not reduced as compared with the control rats. Four hundred days after the beginning of the injections a considerable number of rab developed tumoun, nearly all of thesn tar To0::0479 ! TIFL 0305377
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34 H. Druckrey span, two years after the beginning of the exposure. This corresponds to 50 to 60 lean for human beings. Therefore, as far as results from animal eaperimentation can be applied to human conditions, the mrdium cxposure time or induction time for heavy smoken to develop lung cancer may be longer than 30 years as generally assumed but should be expected to be of the order of 60 vean or even more. This means that the manifestation of bronchogenic canrir occurs only in the mosc sensitive persons and therefore in a limited number of heavr smoken whilst the greater part does not survive long enough for tumour development. This cor- responds very ..nB to experimental results given in the fint part of this paper and is certainly not a mystery at all. But it leads necessarily to the very important praetieal eonelusion, that young people mwt be warned especially, at least not to start smoking too early. In principie the cancer risk is greater the younger a person is at the beginning of exposure to tobacco smoke. Therefore the protection of the youth from any carcinogenic risk must be considered as fundamental for practical cancer prevestion (9). This applies also to pregnanu. A further indintion that smoke con- densates aro only weak carcitagem fol- lows from the faet that the subcutaneous tissue of rats u relatively sensitive to Io- calfy acting carcinogens and that the tu- mour growth was slow. However, the pto- duetion of local sarwmas as the site of injection in these experiments cannot be considered as a nonspecific effect since practically no mmoun have been observed cutaneous tissue of rats is apparently mota sensitive than even the skin of mice. This is especially important for the investiga- tion of csrcinogem as weak as tobacco smoke condensates. Now the fundamental problem of the chemical nature of the carcinogenic mate- rial in tobacco smoke condensates appean. At the present time the higher aro- matic hydrocarbons are blamed, main- ly 3:4-bentpymne, since it is one of the most potent carcinogens, and its pres- ence in tebncco tar has been demon- strated conclusively by many investigators. But on account of the very low cancen- tntion of only 1 mg benrpyreae per kg ssnoke condensate there remains soox doubt as to its decisive importance. Siaee every prejudice in this field may be mis- leading, we considered it as necessary to perform comparative , experiments with solutions of pure 3:4-bertzpyrene. For this purpose two eaperimenu have been started. One group of 47 rats was ttested with subcntaoeous injections of crystalline 3:4-berarpyrene dissolved in a muttsre of pure trirsprylin and alcohol at a deaage of 1 microgram once per week over the whole lifetime In a se. cond group of 46 rats a mixture of I pg of benapyrene and f0µg each of py- rene and astthracene per dose was used. For control 30 rats were injected with the pure solvent. The results are presented in Table 3. With benrpynme I abdominal sartxma and 1 lyrnphosarcoma waa ob, served, but this ady after 1 year of treat- ment, whilst the nts surviving loregee ro- mained without tomour. Since these types of nunoun occasionally occur "spontane- in the control rats treated with the puttr,i ously" in our tsts and have been observed solvent at the same dosage schedule. Ao- in the coettol group with at least the same carding to our long experience this sub. frequency, no causative relationship to the cutaneous injection technique in rats ptov bentpyrene treatestent can be assumed. ed to be most tsxtul in testing substances Only in the semnd group, treated with the for local carcinogenic properties. The sub- mixture of the three hydratarbons, ane T00204'77 < TIFL 0305375
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Experimental inaeuiqationt... 35 ms hsre r'.,15 Wat ctions of !ccd in a alcohol ,ncc per In ase- cof 1 ~h of p'• .ras used. Lid with presrnted J,dominal I nat ob- .r of treat. Inngcr re- ih..c types .ImntanC n "lurrvad •L tISC Sallle rLip to thc a..umvd. :. J cith thc .~eLnns, one rats . eRp°swa sotal dose injresed mal' . treatment aucaba I time daYr bs•ruyyrcm solveat eL,m ~n I I m¢x°`. i mt ll h.nzp.rene 47 ~ 800 106 j 5.5 ' 2(} nr) lrenxpcrene I I nnthracene 46 : 900 116 i 6 4(9 ry) p. rene ~- ~ 30 800 0 ~ 5.5 2(6 9a) ~ ron ~o l Tab/e 3. 9tn;pyena and a muture of hirher asem.0ir hydrosarbou tabd fur runaosnir actir- 6y i. maU dmoIa by <onein°ur rubeulanrou injeetionr in ratl. sarcoma developed at the site of the ia- jcction and one rat died with lymphatic linkcmia indicating a certain carcinogenic L[ft-ct. Therefore, under the conditions of our e,epeivoent, a total dose of 116 tnicro- ^.rarns oF benzpyrene mux be considered is on rhe borderline of the threshold duce. Additional expetimenta to investigate thc dose-response relationship of benspy. n-ne in onr ratt are under way. The raults with pure benzpyrene solu- tions have to be compared with those nhrained with tobacco tar. The corlcentra- liun of benzpprene in tobacco smoke ton• drnvm has usually bem found to be of Lhe order of 1 mg pa kg. With the con- dvnsates used in out experimettu a lower rnntent was found of about 800 mlero- truns per kg, too low for an accurate .,tirsution. Recently P. P. DtYua (10) in f.rnis,crad recormxnded that one should nl.lkc ute of the faer, that by invesrigation Of ..,lutions in the fmua state at the tem- pcraturc of liquid nfaogen (-195°) the hnv structtua of fluorexerlce specta is Abt.linod. Thit me6tod he found highly -nsirivc for the detection and admation ,•f t•Srou small uacea of higher aroresatie hldrurnrbom. Doctor Dikun kindly offer. ,.I to Inake a quantitative detersnination of the bentpSTene content of our smoke condensates, but the resldts am not yet at hand. The total dose of condensed tobacco smoke adminfstered per rat in our e.cperi- rnents was 3.2 g. Supposing a benzpyreae content of 800 micrograms per kg this corresponds to a total dose of 2.6 ng per rat. Sinte, with the pute hydrocarbon at a total dose of 106 ug, practically no maligtsant tumoun were produced in con- nsat to 20 per cent with the smoke coo- detuate under the same cottditiom, it autu be concluded, that the betsapynsne content can eaplain only about i to 2 per cent of the actual carcirtogenicity of the smoke condetssate. Sirnilarly 6. Wynder and G. Wright (11) have already stated ehat the bentpyrene concentntioa is far too low to account for the carcinogenicity of wn- deresed tobacco smoke. One may auume that perhaps eoatd• nogenie factors ate contained in smoke condensate, which promote the aut•.im. genic action initiated by e.g. benzpytme. However, although such mcantinogwia effects apparently play an impottant role in the careinogeoeoa on the skin of tmc4 as with tobaeco tar (12), dsere is acaord- ing to our present knowledge no indira- To0zo47s TIFL 0305376
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40 H. Druckrey tance of the time factor in urcinogenesis is .~elf known. All that we should have in mind is to serve human health and to con- trbute as much as possible to practical and useful means of cancer prevention. SU M>fARY 1) Quantitative aspeees of cucinogenesis especially dose response relaeionthips . are presented as a basis for the assess• ment of the possible risk of environ- mental arcinogens. 2) Two types of condensed cigarette smoke have been tested for carcinoge- nic actitity b,v subcutaneous injections in rats of different BD-sttaains. At a dosage of 55 mg injected once per week for a period of 60 weeks up to a total dose of 3.2 g condensate, corres- ponding to 160 cigarettes per tat, 28 out of 150 rats (19 per tett) developed malignant ttttnours, mostly at the site of the injeetions. 3) Control experiasetsts with the pure sol- vent (tricaprylin, alcohol) gave cotn- pletely negative results. 4) These results confirm the carcinogeni- city of tobacco smoke, as observed be• fore on the skin of mice and rabbin, also on the subeutaneous tisstu of rats. Considering, however, the relatively high dosage used, the low tumour inci• dence and the length of the induetioe time obsetved tbe carcinogenic activity is apparently only weak. ' 5) The repetftion of the experiments in rats of the first filial generation gave the same result with condensate A, but a strikingly lower tumour inddenee with cottdensate B, probably due en a more complete canbustioe. No indica- tion is found for a t-ansmission of the carcinogenic effects to the progeny. 6) Solutions of pure 3:4-bentpyrene, or of a mixture of benrp>rene, pyrene, and anthracme, injected at a total dose of 116 micrograms of ben2pyrene produc• ed practieally- no turaours as compared aith controls. Since the benzpyreste content in 3.2 g of tobacwsmoke con- densate as used in the experiments is less than 3 micrograms, it can account for only about 1 or 2 per cent of the carcinogenicity of the smoke conden- sate. Therefore it seems necessary to look for other caminogens without pre- judice. 7) A 70 per cent alcoholic extract of un- smoked cigarette tobacco injected snb- cutaneously in rats of the same BD- strains following the same schedule has produced malignant tumours in 13 out of 56 rats up to the present, mostly at the site of injection. Fourntore ttemoun are still grmving. The total dose of 3.2 g extract administered corresponds to onn- 16 cigarettes against 160 dgarette with the smoke condensate. This sug- gests that the'areinogenieity may be inherent in the tobacco itself and that the smoking praess should be cnnsi- dered as a denafificatioa rather than a todcating ptocnt 8) The positive outcome of the erzperi- ments with tobacco extract is not con• sistent with the view that cocarcita- gens possibly produced in the smoking process, play an essential role in the carcinogenicity of tobacco prodacta. This even tnore so since such cocar- cinogeaie effaets, although well estab- lished on the skin of mice and rab- bits, have not been observed for the subcutanema tissue of nts 9) Possibilities of practical cancer prtr vention ate discussed. TIFL 0305381
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38 H. Druekrey per rat, corresponds to only 16 cigarettes against 160 cigarettn with the smoke mo- densare. It follows that the caroinogeni- ciev of the tobacco eztract.seems to be considerably, and perhaps ten times, higher than that of the smoke condensates. The positive outcome of this experiment is so clear that no doubt seems to be poss• ibte. But in view of the practical corsa- quences this experiment should be dupli- cared to make sure whether or not ossi- nogenie substances are really present in the tobacco itself. Il so the main problem is what chemical nature these substances might have. A contamination of tobacco leaves by higher aromatie hydrocarbons, resulting from air pollution or from the drying psocess may be conceivable, but the pos- sible amounts are far too low to explain the obsened carcinogenic effect (15). More attention should be given to the alkaloids and to the arsenic content. Since it is known that one cigarette prbduces only 0.01L microgram of benzpyrene but often contains SO pg of arsenic and about 20 mg of alkafofds it seems some- what premature to concentrate the investi- gadons on hydrocarbons only aisd to neg- lect other possibilities. Since arsmie is car- cinogenie to man I feel obliged myself to ttcosamended aa apraetieat contribution to cancer preventions even if it is not the deeisive carcinogen in tobacco, that in the production of tobacco no arsenical itsseeti- cides should be permitted The strikingly positive results obtained . with ewacts of nonstnoked tobaobo indi- cate that perhaps the greatee part of car• ciaogem is peeesostertt iu the tobacco and not produced by the psocer of smoking or pyrol77it. The same would apply so co- can•.inogetu if they play a role at all Therefore the stmking should be coruider- ed, noc only as a toxiating process, but rather also as a detoxifiotion of preform- cd carcinogens. This seems to be conviriw ing to CTery chetoist. For instance it if t.cll known that, even in the group of higher aromatic hydrocarbom, the mmt potent carcinogens are especially sensitive to oxidation, so that the detoAification may be enhanced if a mote complete com- buauon is achievable. This of courte has some bearing also upon the interesting anumption that the free radicals (16) de.roloped in the combustion process may be one of the agents responsible for the carcinogenic action of tobaccq srnoke At least ia seems worthwhile to investi. gate the tobacco ioelf for carcinogenic ae- si.ity without prejudice in order to pro- vide a proper and sound basis for the problem of tobacco smoking and its on- cer risk. However, even if the real nature of the rausative ageats cannot be establislud at the moment, the apparent carcesogerdc risk of tobacco smoking demands prsvea- tive messures. This even mote so beeause it is certainly not the only carcinogen to which human beings are exposed on a large scale, but only one of many. These facts increase the responsibility of both scientists and tmnufaetutess of tobarm products. For a proper asarnmmt of the possible risk the problem cf dose-respome relation- ships must be considered as fundamental. This was the reason that led me to premt the qtantitative aspecn of ratvtsogenesis at the beginning of my paper. In this rnpen I may mention some expetimenu we made some 6 or 7 years ago studying the fluorescence of eigatette smoke as an indicator of the absorption due to diffe• nmt t)pn of Imoking (17). The method was as followe: one puff of eigarettee smoke was blown into a washing-bottle filled with pure nonfluoresoent benaetsa Then the bottle was shaken for complete absorption of the stnoke and the fluotwacence inten- raU20481 th th all an dif etI tita sho un hali cem Sam der Si week Nre The of $n halim to sa) fe TL lint sntokr appan quessn stnokct cigar s TIFL 0305379
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~.runrinc- -:anrc it is Cn,up of Orc nsosa •~:tsitice ' ~~.iflcation ..plc;ccom- , nuae has ~ntcresting ' ..ii<als (l6) I ' "MCFS may ~ dc for the >tuoke. At io investi- :.ngcnic ac- ~ ..,T to pro- I .-is for the ~ ~ nd its can- .~ :ture of the ::,bli>hed at trcinogetde ntl! prCVen- so beeause .rcinogen to ..;;osed on a _::nv. These ;v of both f tobacco thc possible .,r: relation. ._1dxmental. to present . inogenesis ~r. In this '<pcrimen0 _1t studying ',nkc as an I- to diffe- '~ic method tte smoke f i Iled with llun the ah,orption "ucc inten• Expnimantaf innasti;ationr... 39 sity of the smoke solution was meattued cinogenicity of the smoke condensates has quantitativcly. Figure 11 shows 3 cuvettes: been found to be praetirally the sanx for Figure 11. Ftuorerrmue intnuny of bsn:mr jo. fueionr soaainin; ane puff of tiSerette rmoke tok.n b, ,nouth-nnokin; Itrft auartb) nd alter drsD inAafin; (right one). Tbe awetu in tAe midde tuatains Dars 6.nuna. the middle one contains the pure betume, the one at the left the solution of smoke after one puff taken by mouth and the one at the right after deep inhaling. The difference is so striking that this simple nxperisnent is very convincing. The quan- titadve estimation of the fluomcesue showed that 85 to 95 per cent of the smoke is retained in the organism after deep in- haling compared to about 15 to 20 per cent by smoking without itsltaling. The same results were obtained by E. L Wyn- der as reported in his lecture. Since tobacco smoke is certainly only a week tarcinogen, every reduction of expo- sure should reduce the risk considerably. The differences of the abaorbed amounta of stnokq observed with and without in- haling are so sttikitsg that I don't hesitate to say th;t thr rfsk oJ fus,{ ceneeF is not so much a problem of smokinr bus in the first Plaee a problem of inhafiq tht rntofu. This explains in the sante way the apparent statistieal differenm in the fre- quency of lung eancer between ciptette smoken on the one hand and pipe and cigar nnoken on the other, since the tar- all of these products (18) s.fiereu the habit of inhaling is related mainly to ci- garette smoken. Nearly all in,cstigations of the tobacco problem have been stuted with the assumptions 1) that the carcinogenic agents are produced only in the process of smoking and 2) that higher aromatic hydrocarbons, especially benrpytene com- pounds, are the main causative subatance. This, however, seems to be a pn:judice. The results of our experiments corsfuming the caranogeniciry of smoke condensate also in the species of rats lead to the con- duiott, that only about 1 per cent of the effect, or even less, can be explained by its benapyrene eontent. Furthermore the eom- paadvely high carcinogenic activity ob- served with an extract of nonsmoked to- bacco suggests that one should look for other carcinogenic substanees in the to- bacco itself and consider the amoking pro. cen not only as a tostfcadng but rather also as a detosdfieation process. Although these experiments asuse be duplicated, to tnt the reproducibility in other speoies too, the results should sti- mulate further investigation and open new possibilities of reducing the carcinogenic risk of tobacco products, especially tiga- retter. It is my optimistic feeling that technical problem can in principle be solved. I am convinced that it will beeome an interest. ing and stimulating field for the ehemists and technologists of the tobacco indust:iee to try every method of reducing the cancer risk of cigateao u far as feasible Filters can ceetaistlyy not be considered as the so- . lutioa to the probktn. Crgamtte smoking is a habit and it seems unrealistie to change such habita of maa But young peopfe should be warned against an early start of cigarette stttokistg since the high intpor- T 00,?0482 TIFL 0305380
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)cr the lop• t nore EsQerinssntaf inaerti~ationt... than 100 days after the treatment had been stopped 5. the negatice outcome of the control experiment 6. the conformity of the results with that observed in experiments on the skin of miGe. With respect to the irreversibility of the carcinogenic effects the problem arises whether the effects of the smoke conden- sates ate transmitted to the progeny or not. Therefore the experiments have been e.tended to the first filial generation, ac• cording to the recottsmendations given by Getnan and international expert groups for toxicity tests with food additives. The breeding of the rats used in the former experiments with smoke condensates A as well as B}ielded a reduced fertility which proved to be restsicted only to the female rats. Therefore only a limited number of animals were at disposal for this second experimentation, namely 30 rats for each condensate, A and B. The procedure in these estperimenta with the first filial generation waa the same as used with the parmt getera- tion. The carefully prepared condensates were administered by subcutaneous injec- tion once a week for a time of 60 weeks. Then the t:eattnettt was stopped, but the obsenztion of the rats has been continued over the whole life span. With the smoke condensate A the week- l•v dosage was 43 mg and the total dose adtninisteted 3 g per rat. Fifty weeks after the stan of the experiment one rat died with a lympharie te•Yemt• Later 5 atidi- tional nta developed tnalignant-tumoun, ataongst them 3 at the site of the injec- tion (2 sarcomas and I carcinoma of the skin) and 2 remote carcinomas (adrenal and esophagus), which indicates again, that also systetttie uneinogenie effects are to be considered,. espeeially with the con- densate of the type A. The total tumour 3-6I30t 33 yield was 6 out of 30 rats, mrresponding to 20 per cent. This corroborates the re- sufts obtained with the parent genen- tion. ?.B 30 control nts treated with the pure solvent remained without tumour. The condensate B was injected in the first filial generation at a weekly dosage of 53 mg up to a total dose of 3.2 g per rat in 60 weeks. Surprisingly only one tu- mour was observed in this gtwp of 30 rats, a sarcoma developing at the site of injee- tion in the highest age of 870 days. It may be that the improved method used to gua- ~ntee a more rvmpiete combustion in tyte smoking process with the cigarettes of this npe B is responsible for the small ntmour %ield in this group but on account of the limited nutnber of rati no final conclusion can be drawn. However it seems encourag- ing to investigate thee poedbilities mesa thoroughly. On the other hand the results of both these experiments are of special impor- tance insofar as there is no indiotion of aay trammiteion of the carcinogenic ef- fects to the progeny of the f3tst filial gene- tation. Also the lifespan observed in both experimental groups waa the sasne u with the control group. As a whole we have to conclude from the results of all theae experiments that tobacto smoke condensate must be conei. dered as a real catcinogen and this mainly, but not exclusively, of the lorally acting type. However it is apparently only a weak carcinogen for different reasons. Fim1y one needs a very high dosage or concra- tntion tu produce malignant turnouaThe total dose of stnoke eondenates injected in these experimeats (3.2 g) cortt•sponds to 160 cigaretres per raf. Secondly, the tumour yield of about 20 per oent is onfy small. This is in gtsod agreement with the results obtained by H Wynder. Tftitdly, the induction time is long. 77se tsnaoun developed moatly at the end of the llfe- ro~Lo4~s E._ TIFL 0305374
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30 H. Dreekre) am aware that a great amount of investi- gation still has to be done before any defi- nite conclusions can be drawn. For such reasons we preferred not to publish the results of our experimenta, which have been systettutically in ptugrass since 1952. My coworkers are Dr. D. Schm3hl and H. Beuthner. In our experiments rats were purposely used. Firstlp, benuse nearly all e.ryeri- menu until now, especially the basic work of Dr. B. Wy der (8), have been doae with mice and it seemed to be useful te have experiments with another speciea. More- over, with mice skin the special problem of cocarcinogenic facton u included which, as far as we know, does not apply to rats. 7}se second reason was that in the field of cancer production we have eape- rience with our rats for more than 25 yean and we c2n employ 10 different in. bred strains, developed in the last 25 years. All of these have been used so as to avoid special results which may be obtained with a special strain. The administration of the eareinogen was always done by subcutaneous injea tion. This has the advantage of an acros. rate dosage. T7te main reason, however, was, that with this technique local as well as systemic effects can be otae:ved, whilst skin painting is limited mainly to such carcinogens as can be deteeted from their local action. Finally, according to our experience, the stebcutaneona tmue of nb is sensitive enough to show the effeen even of weak carcinogens or small dmea. In 1954 a close cooperation with Ger- mao tobaao sc6entfsts waa initiated. In the first groups of esperimeaa we used agarttte smoke condeasate which had been prepered in their laboratories. Thesa cotttknsatea were produced by a standard smoking machine and collected by the electrostade as weg as the cold trap me- thods. Nicotine was esteacted with dilute hydroehloric acid and the benrpyrene tpes. tent was determined by Dr. Grimmer at the Institute of Organic Chetnistry in Hamburg. Subcutaneous injection was dora; with a dosage of 53 mg per rat, once a week, the condensate being in 33 per cent solun uon in a mixture of tricaprylin and ako- hoi All solvents were carefully checked with ultnriolet light in order to make absolutely sure that no impurides of higher aromatic hydroorbons were ptesent. The control group was treated with injectiom of the solvent, i.e. the mixture of tria. prylin and alcohol, in the same dasage as was given to the experimental goupt After having administered a total dose of 3.2 gof the smoke mndersmtes, cor- responditsg to 58 weeks, the treasmsenc was stopped. The reason for the use of this "stop tet3tnique" was that, according to our pharmacological escperieace, the um specific tmtic effects ate commonly revers- ible within a few days whilat the carBno- : genic action is principally irreversible and progresses even after discontinued trve metc Therefore after the interruption of the applications the unspecific effecta or lesions will disappear with time, so that the development of rurnuurs weeks or months later gives better indication for a real careinegenie action. "Itse observation time however was esnettded over the whole lifespan, which we tried to prolong as much as possible by proper atre of the rats. After natural death each rat was dissected cateSully. For the bistologieal diagnosis we are indebted to Professor H. Hamped, pathologist in Bonn. In comparative eaperimeno two diffo- rent types of cigarette smoke condensates have been used, called A and B. Tbe A-type was irom dgarsstta produced ia the normal way, and in the production of the type B aa attanpt was made to tttake the combustion prncest in smoking as T 0020473 TIFL 0305371
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, -: ----- '°" n( pµysst d•idereaoe &toern test alsimalsand tantsols of In nble 2 the composition of the esrer:fied fatty acds '' `bet° the sasne age does not esst. The free farty adds (lig. 2) of aorm, heart, and serum of the cxpctimental ani¢u15 : pet- .n_ ,E the utam we:eineteased at the beginning of nicotine is shown. There is no segniEicnr dderenm 6etwtas i sppliotion, moderatdy elevated aEtct 8 months and io conaols and trested anirnals. ' the tange of contsols after 20 mocths. .kfter 20 montba lirer .;;,q„ty the eoncenention of the P-Gpoptoains of the test group r.d tht (ti1 mgf100md) Was higha than dsae of the ceottols ~ avr~+n (66 mgf100 en~. As ehese findings are statistically not ^a, significant they must be considered as a chaace peoduct. ~ ~ The values of the Gpids in liver, heatr, and aorn aftet ~ i 20 montfu are registered in table 1. There is eso dideretuq .~ d d ~ tween the trmte an Retstarhable be the control group., ~ tsca however, is the strongly decreased concentration of < oE bodc neutral fat in the liver of the nieotioe-eruttd animals. ~ and the The <oecentracon of free fatty adds in liver, heatt, ~ -crimenc and aorta is given in figute 3, which shows that the q` '. mar of - concentntion of free fitn acids in liver and aoru ot ! the tsicotine•treated group is significantly increased compated with the controls. The activity of lipoptotein • lipase in aoctic tissue of the rsicotine treated animals is :h.a san:e ' signi5owrlP higher chass rhsr of the controls (fig. 4). 'c petiod -.ole dose -:nce aPter sed that ~ -:d been ~z za5 ~ . content, a ral : u . s a e c .Lnd aorta ~ 9 hours. 1 pots, and • a sas is in ` te0i -a u..... '. d q Plt. 3 Frq fatty acieL in ilver neart ann aorta at ehe ene of tne eenerlsent (aU mentha} WM<e ban: contrelr tutanM Dan:.reten t[meMA] Heart Aerh I towards Pit. 2 Mt• 4 - Frea fatty atlet In the blood aflef 9.13 and 20 montbt White bars: ActlNty of li9opetein IIeav In heart ane ror1\ sfstr 20 mentha the Con- eontrob; ratNea trn: tn\taY (FFA - rret fatt9 acida)• b~hlta Ge: eontrols; fiatchM eanc uueM e, Clfe riSt change in Tab. s age these e1914.In oraw afUr 10 raentha, L'Llus In mtl100 e ffeh +eieht, nautN fat rflealatq (ess4M) 'i. .~ sigttr : . N.are Lt.et Aarta ' ftleellM CaalLOb Nketloa Controt. Nicvtlna Gntmb r <reaeq trntta treatea f' Tu4lnylae 31N asls a5tl Sena 9a1a 9a1a ` TataltbohWm ' 159 151 431 395 ]91 353 tl 13 FratthaltapeW BO 5] 101 79 6556 ~ EsterIllM I\ety aelY I1a9 laBO 1526 ISM 0421 s Fnmpnaneb 1513 t55Y 3035 Zt99 SIS 795 , Seeiyfat 100 19e 45 411 820 $704 TaG l tatuinen fatty adCa In bluae anu 20 months. PefoeataP \la'tDvebe (maam) EsterlOM /itty adds AwY . ~ C-Atoma:eaubl" bcnM Centfnla Nitetina 14 9Al 1.71 16 29.11 20.03 - saum after le: { 6.11 5.46 cM. IB 6.11 8.15 :•nlr 19:1 RSAti 32.96 . :atan tala 1936 ]6.03 16:3 4.37 3.80 ' ~:a 02I 09J • a . CannW NYn NIntW Senq Controls Nlcotine 196 1.05 0.81 O.N ]2T0 18.31) 2100, 22.25 3da 2A9 3.01 a.b/ ll.TO 1116 lLaa IOAa 19.91 YIAe 2130 1L.1] M .33 . 33 lf'.aa 35.Oe 39.17 a.53 2.70 2.76 346 T.99 6J{ 16e 21+ ) rp.LaflntWNfanMLWlerro T-0020430 0 :9A7; Hdt i Z• tlin. (yrro. yue, g}empn, i B. jabry 19701 Hctt 3 a3 TIFL 0305388
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!n P ar a .t ~ lt aI CIGAR6TTE S3fOK1NG AND DOOS-XAbf.l10ND ET AL 749 Ta !,PweMbge Ola/rfb900n o/ 8eGiena by Grade 0/ Each of Five Types Of Niarobgic Changes in ule Lung Pannehpn. Noe6Ner. rluntiltar. Oroup N• Graup n• OraaeefQa Aiilen O.ya o.ya oaya Days 0•Y9 37.49!(%) lOOd]!(%) 676i99f%) !]l9!(%1 50047!(%1 ilErefls 0 ... ... ... ... ... t ... ... ... ... ... 2 23.6 ... .. [9.! . eA 3 ~66.7 47.6 9.3 7i•4 47.6 l•5 9.! !L4 91.7 9.! 47.6 Tor,l 100.0 - 100.0 100.0 toao 100.0 EmMya.n•e - 0 t.i I ]6.7 ).1 t.2 639 14.3 2.3 2].6 99A 96.6 33.7 a6.7 Tatal 100.0 300.U lo0.U 100.0 100.0 pa6•lit.em meeu 0 1 ... ... ... ... ... l221 1i7 I.4 l0.0 143 2 47.6 93.3 97.6 l0.0 eSJ Total 100.0 100.0 t00.0 100.0 100.0 T111CRne11 pl 6s of eapnWaa 0 100.0 64.3 $9.3 97.6 85.7 ' I ... 35.7 35.7 2.4 11.9 2 6.0 2.4 Tatsl 100.0 100A 100.0 t00.0 100.0 TlwGtneY 9t 0 Yl.ura 2.4 4.6 . 2.a ' t 76.2 26.2 9.5 64.3 _ 30.9 2.3 2].e 7L.4 90.5 30A 66.7 TatN 100.0 100.0 100.0 100.0 100.0 noofe9p No.atfee09 6 6 12 6 6 . 4i 42 94 42 42 • Oraup H np A aap 4iN in G{Mnent ye.laW ct9ma fram N, 2.Wo from group F. 39% Conlldermg fndi9iduel d085, the d1I- from pW p L, and 4L7% ttom group H tec.oro! between groups F and H and be• (Tsble 4 L and H are atadstic6tly d Fig 9). twceh groups Co ' the Wilcozoo mnk sum test 'g individod dogs, the diE- signi6eent by fex.nus geoup F and H and ba- (PG0.0001). The d'$aana h9twwen tween L and H ate statistically gmup. signiBauL by the Wilemcmt esn7t sum t66t (P > 0.05). (P G0. d,.-we will d,.-w . 1). Thero was no di[tersnm bo- 1Sen. T4ol tween gm findings in telation to the lime of deeth of F and L Thickn the dogs that died before day 875 and in of Pleura,-'fhe thidanw of the ple wa9 evaluated mSrade 0 in comparison to findings in those that were 30.40 grade 1 in 69.6% of sections from killed. group N. Sections ftom the Iwegs of Lwo dogs which Thicltltels of grade 2 or 3 was faund in 0 had smoked only filteo-tip cigarettes and 19 of seetione from group N, 10% from grou F. 21.4% frotn group L, and died blfaro day 57 showed a slight degree ot 90.5% fro gnup H(Table 4 and Fig 10). 6bea.si a very 9light degree of emphysema. Arch Enwen n HMth-Yp[ ?7. D.c 1970 TIFL 0305401
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CICdRETfE SMOKING AND DOGS-HA.ILIfOND FT .11. Tat I and latar lust weight Howqver, the groups of dogs did rot vary signif- ly ia this ropect. o dogs of group F and tuo of Btoup L before day 876. Their weights shortl.y death were approximately the same as p start. Of L group H dogs that died Areh Enu4un Healqr..9oi 21, Dec 1970 -1o02ocoo f - r it.~-lunq ParanchYma W a yreuP N r.pn.mpMlnq Flq ' Coq ryIHG cn pay 903. Grad. 0 M,pia anA emphr• sama ItroCUaC Iram x 30)) raus4 death. Dog H658 died suddenly after smoUin8 his fifth cigarette in the morning He bad pulmonary flbroeia and ero- ph ma in all lobes, the degree was proba- bly ' ufHcient to account for death; a large n r of granuioma/a with brown pigment and at in all lobes. shown in Table 2, noninvasiva btao- chial veofar tuupes wete found in the lun of 12 of the 28 dop whirb died and in ive bronchiotoalvaolar tume[a were fo in the lungs of four (dogs h626, h649, H71 , and H753). These tumon will be ibed in detsil.ia th. second peper on this ~ubjectrr which follcws. ght chanstr.-7rr qenerai. the appetite of e4nokin` aa well as noaampkiag dogs sa good. They usually ate all 400 gm of tood Rovided each day. n t dogs ffachta0ed somewhat in wefaht. A f lost weight and regained it; a few TIFL f I t 0305398 , I
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CIGARETTE SMOKING AND DOGS-NAMMOND ET AL 747 CPr a Imonal• (pulmpnary tmPhyfem. 6 li aus WT n5ht aVial anC ven 'su4• tma.itmtnt ef natA/ Oulm nary Inbrp9an B(On CPM4mYMal moi nen of toa< , Day. 57 ThreuOh e75, Da9s e) Oroupc F. L,N,hanCN Fint(•T/p. Gro4F l NOnbtP, Gr04/1 L rlCnMtM, 12,040 N NCnNIM. GrOYp h NPnsmOMry, GrPVII N TPUI t 2 5 9 3 1 4 1 .. .. 2 .-. ... z l ... 3 2 2 )2 12 a z5 19 1o L2 2s 6 65 12 12 24 36 a 9+ eOI tnt+t Eo{sapParmtll tie0 ot t cambinatbn Piqusas(q. pWrnbnary amaMysamt. PulmCnary rieievs n. ettn tne na4 tw.re coiMlban. pW.nanary iNa2UOn. an0 prenenoPnaumOnu). In mlf ta01. u0n Ooln Is ctluili.a attpra0a tP .ntt .PP.•,b Tabl. 4--PUwrb99 D154)buDOn of Stetions by GnM of EscA of Fl.. Typn at Nialo/a9ic Change In Lue9 panncMn+a . iop (IlOht avd OraCe »0 /bNVy , ar.o Or.oc Gr W. ol ConCitlPn Np.vntYen. Gro4F F/tenTlY. OreuP NPnnltar. Groue L (%)' Nbnfrntr, GrouP N(%} FlbmsN 0 10.7 ••• 1 69.3 5.7 1.4 ... 2 .., 52.9 21.4 3 ... $5.7 64.3 6.3 4.5 5.7 12.9 91.7 TPba 100.6 100.0 1011.0 100.0 EmpMNma c 100.6 L.a ~ 1 7aa " i.2 1,3 12.5 2a3 99A Total 100.0 100.0 100.0 100.0 P.C.pM. attW~m.nta 0 •c.6 ... ... ... L 66d 77.1 2.4 2 22.9 0.6 97.6 Total 300.0 100,0 100.0 100.0 ThkMn.q af arttHOlerals 0 100.0 97.1 97.1 584 1 2.9 2.9 35.7 2 a0 TPbI 100.0 100.0 100.0 100A TMeYnan 0/ p~tWa 0 30.4 2.9 1.t • 1 69.6 97.1 ]7.2 9.5 2,3 10.0 21.4 90.5 To W 100.0 t 00.0 100.0 100.0 No ol6oltt 6 10 10 12 . Nb. Pf atctlons 66 70 70 84 • Gaps IubJ aHtr 975 Eayf ol amP\m9. Axh EnP'von Htnl)h-Ve1 91. De0 1970 T ppyo5~1 TIFL 0305399
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Expenmentof invertigutians... 29 :I dcath. . wcrc zs J're was, ic but on ~Ncrcascd Lc group mg per (1p mg. tumour ,he total losc aba- I ( Flgure +nations x Ts/At mol de.. rat. a' de. ~~fnut.r./ .nttnetia. 100t 500: T6erefore rriskof 't coursa af peab. icologiol experience. From the results in fi, ue 5 it can be concluded, that below a cer- tain dose the probability of cancer matti- festation becomes so low that it can be neglected. This indicates the edstence of a threshold dose. But two things have to be borne in mind. The threshold dose cotuerns 1) only the total dose, i.a the sum of all successive dose administered, and 2) the manifestation of catxer. When wn- sidering the carcinogenic effects of succes- sive doses, however, no threshold droes caa be demonstrated as shown before. Fue- thermore we have to distinguish becween the cireamstanca of animal experimen- tation and those in the human situation. In animal experimentation dase-retponse relationships can only be investigated pro- perly down to about 5 per ceat proba- bility at the lowest. For lower pertmeaga one would need heratombt of anima4, which is not feasible and I would not like to take the responsibility for doing this. When, however, linear dose-reepona relationships cdst then eztrapolatioo to lower probabiliua is peemissibk For human beings, however, the assessment is necessarily completely different A ptttb- ability of a few pereettt, which meam nearly nothing in animal expertmenta- tion attd annot be proved in a quan- e titatfve way, meatu, in contrast, a lot of human beings considering the hundreds of millions of people which may be expoaed to eertaitt atcinogene. Thero- fore we havc to extrapolate the dcee- respotw cueves to probabilities in the order of 1:10,000 to give mffident sfety and to be able to guanutee noararcno- genio activity (3). This is an a.pete of highest practical importance. But the strik- ing point I want to stress once tneta is that all contiderations concerning thre- shold dosn emst be made in rdatioo to the totaf dose of exposure, and thfs fur- thermore not only to one careinagtm but to the sum of all carrinogens which may be present in the human environment. From the experiments with limited ex- posure to 4-DAB reported here another conclusion follows, namely that the induc- tion of cancer includes at least 2 ptoces- sa. The one is the carcinogenic acdon proper, this means the effects of the cau- sative agent, convening normal cells seep- by-,tep into cancer celts, and therefore happening on the cell level. The other is the multiplication of the previously pta duced cancer cells which, according to the total dose administered, pta>gmsn eonti- nuously as an autonomous growth, even when the expoaute is discontinued and the causative agent is not present any more Therefore, since two psogrcmve eventa are apparendy involved, the ardnogene- sis as a whole is regarded ay an accelerat- ed proeev, which risea to the square or - even higher power of the time, as already suggested by experimental observations (6) (7). T3tex are some aspecta and experimm- tal raults that I wanted to mention for a better underitanding of the pmbletm under disetasion before I come now to atr experiments with tobacco and tobacCo smoke condenntes. The main problemt ue these of coune: Is tobaeco tar or stooke condentate really a carcinogen? And if so, what type of carcinogenic substance is contained in it? Does it originate from the pyrvlyrit? Is it niated m higher aromatic hydtorar. bosu? Or, on the other band, is ttAta¢a . smoking only related to hsng tancere in an unspecific way, being perhaps a mee m- rarcinogenic factor or a complete uueped- lie irritutt? Ia the discussions of these problems them are se matty diwepancia and in- wttsisteada that it seems highly advisablee for roe to keep to facts and expafinentd results and to avoid going any further. I Tt,u2u472 T=gli 0305370
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I 756 ClGARETTE 5.1(OHI.VG AND DOGS-AUERBACH EY AL Tam6 1. DaM pn Dogs With Lunf rulRerS. rrpe of ru+ner and Lpbe Jn Which Tumor Waa Pound ~ Af.se Loeea wnn Bren</rote~ NwNMTUmorf{ [arh 5puemaua GII G ou p O+Ypf MatM Mo.ol C."aanNef Death (0) ^NOMmaNw n.rssne BrpneMM Cxamms GraupN Oen empkwf)N 904. ... 5.1 U 9C4b ... 4,9 RA GreupF( rilla rtip)F 878a 6.161 5.1 U 379a 6.170 4.7 LA a85. 6.224 5.2 U 890a 6.269 5.4 LA GreupL( hpn lilla)L • 347 1,055 3.5 U.LC 612 . 2,6.7 5.1 RA 676a '~ 3.103 3.1 LA,RA 87L 3,107 5.2 U.LC Be2a 3,127 5.2 U.LD 596e 3,183 5.3 U.RD 899e 3.195 5.4 U GroupNd non RlteqN 133 519 2.5 RC 259 1,343 3.3 U.RA,RD 563 3,404 4.7 LG.RA 716 4,689 5.0 U 753 5,030 3.6 RI LA.RA.XO 760 5.088 4.2 L A 898 5.970 5.3 U 876. 6,129 4.9 ' LA,LO.RA 877e 6.138 5.4 LA UBB 878{ 6,U7 5.3 eA LA 8824 6,18.1 5.4 U BLL 6.192 4.7 RAAD.RI U BB66 6,210 5A LA,RA LMB BB9e 6.246 5.0 U 6991 6,236 4.9 LA 692e 6373 5.7 LC.RA 6920 6.273 59 LARA B9b 6.316 5.2 RA 8f7B 6.218 4.5 LC LA Oreopn RRer)b 60E 3,769 4. 6 LA 626 3.928 4.4 U.RI 649 4,143 6.0 RI LARA ' 794 5.400 53 LA.RA 70020520 ~foa p61nB6optbepaYpfpeatnln6iGtseNenumberel6aysNrmeehqCfaneFn{.TnuN[n.a6fatews ! h:.i'.f<~1 tna C.Y C C.atN p1 yeff MB4E aR.r CaY 875. t LaRa 'aNleba,UaeflurE.ae.LO:uRabpnrpma0c.l0:rI6M.pk61.RA;ryAttar6nn,pC:riBntinlermlU'rh, ' fic•_'".f:: RL riybt fepnqfm.9e, RD; left apicai bran6n bronClluN UBB; INt n41n EronMUS, LMB. , Arch Enriron HeOIth-Yd ?!. Dte 1970 IIII • {/ a :'J:CC d.-:mc[ !o.^ rtiC 0', ~tt` de[[e° L , Tr.'t G I 1- Ca•. ;:r, iaIL tr-_;.lC pp:Gn-le• pLL:.•A10L tF:a b: pio[IC' jlytcdOtt tl:'.:.YY3 t{0' 4g_ 10z "~~~SL'^.:a n] ' ~ TIFL 0305408
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750 410W 0 SYp DOCs Ga01I / FlLR.T'tY CaA I GICYa l /q fILTfl1 40I YO I~V ooa eanu w lilf~a ClCARE7T£ SMOKING AND DOC3-HA:1l:VOND ET AL 1 I 1 0 t 2 0 I 3 4 3 I flq 4. raN 0f fCrvfis found in eauY of stm flRlma f T 1a<tl Of t1N !pf Mat vNM 1i111M ~ after 875 caYS. Eldl d9t rcpresmts ona faeeen. The sevm Eota an e lins rpMent Ma Uvsn JK• . :iena Of Iv Garanc/ymY fr01n a paRicular Oae. i 09 6. rapb ttYn.iry yucaa Of faetbns rM ab 7.-GrapY sYaWig O.nwt a seceens with ~ I , prea. a e 9 across in duas 0f 9mupa ta: 5 L 9raas 2 ar 3 s/rpnrurns ~n deps N qnvps N, T, and M tMe ran qllad afUr 873 eayL L an0 N tM1et wn MYMY aay 875 Crya, .a Gq Patj•lilLno7IDa1 thi 4ewfel ple. roanY sect' .3ettl069 In differ atuch ticnad ahoc I$12 were . like attaflta 2) wete Eov: dogs. Table 5 s: Arch .Fnoircn fledth-Vot?1. Dae 19:0.,r••n~OSn4 ; ~~ TIFL 0305402 CMp[ OI [YnnfW 1 2 Fig S,--Gnea of empiqfama bune In .asN uf favan faetleni herrl eaen e/ Me eeea 1(Nt ara Fillee after 875 da9a. EaN dot rpraaenh ana sae. . Hm. T)fe fauan deta m a Ilne rcCreaant the eeM I aaelimn of IuM Ganne/iyma M1om a paMeular da9. ~
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41 nlsion of the pro4my. ,(" wone, or of , IaMne, and mtal dose of "rnc produe- .,, compared • Iknzpyrene ,~ .moke con- .prrirnentf is :can accuunt r t-ent of the '-Ac conden- itcccssuy to : without pre- -.rract of un- injected mb- ~I., same 8D- :, .ncl has • :,ours in 15 out -•-n1, mostly at t InotetUmOUA -:.S dose of 3.2 ,nrrceponds to ; 160 cigarettes .,:c. This sug- -nlc{ry• may Ise t~)f and that uld be ceati- i mther than f the cxpeei. 'n is not ccn- uc tccarano- 1 iLe smofting i( rnle in the ~<n ptcdueu- I tnc coGar- at•Il ptab. v and rab. :rad for the rancer pro- References 1. Druckrry, H., Klia. Wocbmtchr. 22, $32, (1943) 2. Druckrey, H. a K. Kepfmuller, Z• Natur• forath8. 36, 254, (1948) Duekny, H. u. 1:. K6p(mdller, Dctb orW Wirkung, Editio Cantor Aulendorf, Wnbg 1949 Druckrer, H. u. D. 5chm5h4 Jledia. IClinik 55, 648, (1960) 3. Drvduer, H. Armeicuttelforrehg. 7, 449, (1937) 4. Haddmy A., R. J. C. Haria, C. A. R. 1(on and E. M. Roe, Phika. Tranraee Royal Soc. 241, 147, (1946) S, Sahmiltl, D. u. R. Nfecka Jr., Z. 1. I.Geba forxEts• 61, 230, (1956) - Druc}rey, H. Arclt. eap. Path. LL PhamalmL 238, 67 (1960) 6. Bluta, H. F., Cateutosenew by ultravioke 6gh4 Princemn iinivenity Prees 1959 7. Drucluey, H., Arm.lmitulfcrxh8.' 1, 383, (1951) S. Wyndery E. 1-, 1:. A. G.aham and A. 8 Croningo, Cancar Rea. l3, 835 (1953) Wynder, E. L. and D. Hoftmann, Caeeer 12, 1079, (1939) _ 9. Dmckrey, fL, 5rrablmrhempie 93, 165, (1934) Oncolo8ij 7, 155, (1954) Acta U,do Incera. Canc. 10, 29, (1954/ JO. Dikun, P. P., O.rcdosij 5, 677, (1959) 11. Wynder, E. L and G. Wnght, Cancer 10, 255,(1957) 12. Gellhom, A. Cancer Rer. 18, 310, (1538) Roe, F. 1. C., 31. H. Salaman and J. Cohm, Brit J. Cancer 13, 623, (i959) 13. Sm:h.ri, L D., K. C. M. Ran and V. R. Iihauoikar, Brit Med. J. 4922, 1111, (1953) 14. Cooper, R. L aad J. `L Campbeq Brft J. Cancer 9, 528, (1955) 15. Kennaway, I. L. and A. J. Lindtoy. Brit. )led. BulL 14, 124, (1958) 16. Llonr, Jf. J. J. F• Gibson and D, J. E. In- gnm, \atun 181, ICOS, (1958) ' 17. Scbmihi, D., U. Consbrvtlt u. H. DnacL, rey, Armeimittelfaetchg. 4, 71, (1954) 18. Croningv, A_, E. A. Gnham and E. L Wynder, Prx Amer,' Ara Cane- Rev 2. 269, (1958) DISCUSSION Pro/. 7flein: PrnL Druckrey, whm you am dealing with nu how do yon mana8e to Inea. lue thr site of injection? I rhink rhu mutt be a pmblam• Prof. Drae.krq: Of coune, it is a prablmt, and we have the eame type o1 problem in, for io- aranee, the skin painting technique, but with a little aprirtw it can be done ptoperly. Prof. KLet: You don't think that then is a diffetence in this reapeu bawem pun eatdne. gena and toDacro snolue mndenate? I mead the .roluma injected and an on. Prof. DneYrry: The vohuttp an alteaya dr .une- We haw taken as a prindple only to have roM varlabfe factor in our eaper®mta Prof. Kfria: Pmoided there aee pmmetin= mb, atuar pt.rent ir the tmoke condenwe, do you tJqnk t6at they would be dirtsibuted aver a laryer arnt Prof. DrtrMy: This ma. be a, but on the n,ker hand the potitive outmae of our saperb mmu .rith eatraeu o1 ulaaeked mb.cco rheo" that either muat this mcartinosan be pnemt aM reedy in the extract or we have to deal maidy vdth a pure <ardoogauc action and the mtu- cno8ra ir only inertating ehe eftacr. Prof. Klaia: Are the typa of tumeun obeain.d exactly the tame with tubama exaact and with saeke eendmree? Praf. DrreMy: E:eacd7 the aamr. T6e tmrour yield was grt•anr with tobaem eatne than with anoke condensate and I think it is .err plauuble to a chemia that a combustian pts ces muu be considered nm only aa a tmdtarim pmcm but also as a deroxintim procesa tuaa we kno, thae many wbrtmca an droeyed in dfe combustion and the more re the more complete the cemb.ution ia. I think Dr. W yvdet wiB agree with me that it is advisable m tendc the condwtdoe in robaern mq4ie8 a eempler aa potribla T U();;0484 i _. TIFL 0305382
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CIGARETTE S,VOKINC A:VD DOGS-H.111}fOND ET AL 745 C:din¢ = 6•io. , ;;i!1ed fi99. 903 anCP dogs l day died; zuo F +r half -•.ost a death d the mean ^nt. -es of ;:y of Toked. ,.d 6>. do; _'. I on :Ci Of each i'dof -Il had .t lea6t iound was 1 to be Im of -ec of •Y ap- dog's dog's •re due d em- All ten . ns H ing. Ilt o!arge- "' por- -',c than !lphy- uulmo- In the th~e a left w in Table 2.-tAoddit/ gspariaeee ef ClgaetU Smok7eg and Ronsmoking Dogs From Da7 57 ihrougn 673 oay N0. f al CIe.. oestn etd 259 1.31 271 1.44 287 1.5 289 1.59 3<7 1.05 360 2,l <t6 2.3 e66 2.3. 517 3.06 563 3.40 606 3.7 626 3.92 6,9 <.1< Oy Dey and Caua. at D.a/h• op.tn.(X) ii1Gn TiO. Oeouo Nao- tiN.r, Glaup Nen- tilGr- Group Nan- filtu, Orevy Non. amolur/. Group Nen Invu Inva- aivo sWe Tumor hmOr s L N n N Princp./Caua.e/0e,th (1') (u) ' X Poimpnarymrarcuon % PulmpnJlyinrlretlan % Uncorbie T % BloneM1OpnWmann _ x , BrnnanopnWmOnii % PulmonarY /nfaralian X ' BroncnOpMUmOni~ 6 YWmOnary+nrae0ibn T % Pu/men,ryinfarctlon Z arCnchaOneumonla.Nn.eaepe. X Uneertaln % 6sa~auaneftana r a ,cqrahenaftead X Nlmanpryln/sre110n X PWmpruryinbrql0n % PWmoeary pmp6ywm. & ebresn X Pv~monary.mpnys.mp 61i0ro1b T % Ca1 oulmenele T x Cor polmonel. T M % CoI pulmonaN r M X CW pu/mOna10 6 pulmona rnbroean M X CN pu1mVNM r M X Cw oulmenab T % Cor pulmonpM % Pwmen.rylnf.renon6pelwlmonY. z Ccrpulmnn.a •T X Pulmenaryin4reu0n T z A,Irnomry InfareJan X Un<pn.M T 2 2 12 12 10 to 12 2e 8 11 12 2, 38 8 the vaead ava and swerd had thrombi in othee Follr th. (h19& H2O8, H239, and x~7) due principally to btollr}mpoeft- trtonfa, one irofma, pulmoltary Infarction end, ia sorond, puitmmty abe(xes wnteib- uted to th. All four had moderately ad- yanced ry flblosis and slight to mod- emte em y9ema. At au y, food particles wer6 found in the la of orte dog (I347) and in both lax and tlaches of another (F390) 1. the The lun of dog F380 were milupsed. One ot thex oga de.d suddenly tv{file smoking a cigarette and the other,'shortly after amok- inb Asphyxiation resulting from aspiration of food appeaeed to be the major ause of deafh, but reduction of oxygen supply or aNts tOXto eHecta llxy bava been centribuP ing nnua Tne principd tause of der;th of three dogs (H133, h289, and H868) is ttererfain Dog H333 had slight to modetate di8bu 5btosis with emphysema in all bbes of the fmfgs. Dog h289 died shortly aftee the morning smoking session. In this dog, pulmonary fEbr66is and emphysema wers present in all lobes and orgartized btanzhopnerlmonie in the left dia9hnlgttmtic lobe, but these tnor- phologic changes did not appmr sufficient to Arch Enuiron HeNtL-Va! 21, Dee 1970 TIFL 0305397
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CIGARETfE SHOKIJfG A:YD DOGS-AUERBACH ES AL .ien I~~'n~baY~insan, X K01• -7 -~ Q~_~~ ~ T Fig L-MI(Mpe.w vi~r ei aneUM IKlbn e/ wm. an~ aa In FI/ S.Iwin( aW~neF 0 la.M mwnbtirF (am.w./ in arr al im~ = l. Ir 1 Yi/ 2-Mip1~..(I YiM 0 aneHwY Nna/ I.t4en e1 L,1b IM(Y/nj /ams » in Ii[ !, 9stun~nt mFml.an. s aef(M ewr ~e.w peRbn Gt bH41w (.Ilvw nruw.n,i,.w X s1G. . ATch Envisvn Hnlth TIFL 0305415
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-U D 0 0 0 A V N
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CIGAREI7E SA10XfNG AND DOGS-XAMEIOND ET AL ' 743 able S.-Oa7s o6 F6d1p7N0 dfa/6 H6eql6s of GroupJ F, l, N, h, and N .J balf !•~rinE isct oida. c'ets vettss ainder dop but J rin5 : Aogs ditftuttoe .sh o! / Blter dpe >n th. 11775 dqa 7 .~ (n 661im6ti „ r aaim6b . :~r end ~ of toYea n 6 nu °Y I ren5nn, Ti . s~e ~ cunaumed der67• ys5itnrnup6M _.p et.nn ( .r u .uun.p( ~) raunpat d 6(yrl 0ldestda6' q ~ WNint at sL Me.n vN91 ti6nNet da NeeNest d (day 1) ,x6(R) Y6(Ib) k6(Ib) da61n875dayat eipntteeperday 0, aa 0prene pw 0ie(150Jb)/n.n aat reiprelte(mf) eetperNtan9bOnlV 873 dayw per da6 eperda6 oo3qe in 67 d.yr rr/6tNe te sLrtin6+« nlr Gnma af r Cw 0eun0 pt.d6pt Gramraf tMepwpundN r.ynt Fllter.nY. Nanliter, Nanf,INr, NanNtpr, Npn• vne4ry Graup F Group L GrouF N Group n Group N 12 12 24 38 e 2 2 12 12 0 16.7 16.7 $0.0 31.6 27 2.7 2b 2.7 2.6 2.1 2.3 l.6 1.7 2.4 3.1 2.9 - 3.3 3.6 3.3 11.3(25A) 10.0(22.0) 12J(2a0) 11.6(25.1) 2.1 (20.0) 12.8(263) 11.3(25.0) 9.3(20.6) 13.2(29.0) 1{S(31.9) 13.3(29.3) 17.7(39.0) 13.9(30.7) IU.0(22.0) 16dP63) 6,163 3,103 6,12V 6.12! Nenw r.(r! 3.94 - 7.00 7.00 ..• a2.1 21.3 s2.0 328 ..• fYtw.Np NantlNw Nen614r NanNn6r 17.6 34.3 3<.8 30.9 1.17 1.85 11811 1A6 1093 103.5 207.8 207.8 7.19 6.66 11.12 1L12 4.17 4.12 6.31 6.51 ' 0.2p 0.22 0.4 0.35 • Tne anwY n9 dale wn driOM tnto Eroups F,1, N, ane n an eb 67, r rneae 66 apnly anly to da6a thMt turrNW e75 an ar tenpr. - • OOp of up L N. 404 n.,Maad NItw.Vp d9wetNe du-e . M1tINnE p.tlael at tIM abrt af tM nperlnnM• butamplu6 tltlerCpr.npvlMrehw. i aaookin( filter.ap snd aen- mneh .Itpo6un la niootitr Y Erottp L - wa6 tak6o inta 6aount in cum• Tbe 6Ebrw LbNed "«Nbwlent autnb6r ot ': tae 6td Irieotine 6otmn1t6d durinE nE6Mte per day for 68.0•kE (150 Ib) mpn" in I ain of the anim6l w6e tenaiderW Tpb(e 1 se haaed upen the 6ottmplbe th.6 . eNMi96 doep,171e body wiybt haldutE aba)W e dwp batata516, 2elatte d66- the start of th. 6Eperimntt was Ve is Sa'stsN1 Prnpott3tuul to body e+i[ht• . av6ni9nt me6sYn af tira For th(9 7tiee dWn6 are (al.nded only to shpw that, t sho.. 6rama of tar and nicotine in n16Npw tn sir.e, the dop in this esyeriment 875 days divid6d by th, m.nn smobad np maro ciE6tNt6p per de9 on the , _. i sfattint we Ekt of each Roltp of attimeL. H7 awtaE6 than tn6ny habitual attmkeN. . ... dota ~ this (ndex, p b had lower eHertiv6 exposu» !n otder to perrttit hi6f6ioEia erpmin6tion ot . to tar aad 'ent(ne th6n 6roup H: {2oW L hsd lutq utwt6 fnm 6mtF6 af dop thri h.d "2 pnr' II half that geoup H: and Ooun F had 1,06 rtneked 6bout tN 66ta6 IenEN of t/m., it rras ' _ '-°'dinE ! tirln a6 m eb espoeure to t6r and 129 titne6 as decided that• wMn ha() the heesle in any v The i h Enruron ' flsallll-Vpt 21 Dae 1970 QQ'.'.Q49"1 ~ A n: . ~ ~ .
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Effects of Cigarette Smoking, on Dogs 'he following original crticlee by Hammond and +uerBaJt « of are haeed on uelbds- aig ed stud.es, conicientiuruty executed. The ar.. inat oersfons arre the sab%ect oJ contracer, +y in thr lay prem, statements by the Tobacco 1 fitutt, and uy the Sur`eon Gerterd's o/ltct- It ' unfortunatc that research on anokins ..a o/t suoko panfonofe rather than drtaehed Ea tselNOlteaty, was patfannW an 97 nnla bea• Ag but eight (group N) wen tteinN i0 ke cigareltn av.r 't4e flr.t 56 daye through tu ' Iran e elguntt. halder to 6w ener.eoetomn. 01 tM 6f nnaking dop9r two died and ane w.e wi drswn dud: g this paied. On day 57, Me rw m ing 10 dogs wen divid.J Inb four groupe ipted to vsrleue ueeuing eslegorlee, sorn. ing 611ehlip end othen nonnnee dgr.nea Alny an d.y 2711, sN swvWing dogs were and lung seatlaaa wen eeuAnW mimn. kaly- The tueyp d 1M 1" N dage w.r. nohtlN whtle histepetlabgieet ehanges wne hi aH snlOklnrJ degL Or661ap1 ChM1gN wesa en the lnpe W dope smokinp nanhhee dge-. meat hese]y. mittsd fae pua4atl^a Suly 29, 1970; eeeepetl Jaly 4p. }am ehe .SmniC.a Ctaa.e Sonely, lae.. Mew Ye~dt tlk. fLmmrad ar.d b4. Cer9nkeU. eed the Ve4~ea Adm6vrtntioe Hu.piW. Fat O,.np, NJ Auw6a3 end Mr. ICinoesn). Mlan tbe oc±entifle serien of the areting of ItM 8obd ot DSMtan of the AnNrioa C+nor , New Yak- i-eb 6. 19:0: and in peet befa. 8ieliea an Diar.es ot the Cbst at the 119th teapnWw of the Aeeri.v Medid Aag aa Chiayn, Jue. 4s, 1970. teodat i to Aauniran Crnc.r Saesty, Ia4 2I b' 42ad NwrYork 10p17 (Dr. ffammmd). L Design of Esperiment, .1Iortality, and FindinRs in Lteng Parenehyrna 8. Cuykr Hammond. ScD. New Yerk: Oscar Auerbaeh, ,11D, East OrmryR NJ; David Xirman, Ea.t Onange, N~, and Imannce GarfNkd, Sid-Netu York IN NUMEROUS epidemiologic and his- tt>logie stvdiee, it has been fotmd that adverse health elfects of cganlxte atnokulg inazea: with increasing ntcrben of cigarettes smoked per day,14 indiotlng a dose-respetne rela- tionship. The doee of tar and nicrotine de- livered in the smoke from a aguetfe an be reduced in several ways, induding use of a filter. Thus, if tar andrnim/vle are respcta5ble mainly for the ill effaW of smokmgL then smkins edg9refte6 equipped with an efficient filter mAy be tes )smdul than smokatg the same ntcnber of identfai eigaretles not so equipped. The press++t enperbernt was cco- duckd totest this hypothesis. A teasonbly atiatactory enimal model should texet the following speciflrations: (1) The animals should inhale atnfoe daily di- rectly hom cipuettq and, telatiw to size, should smoke no map taga7ettea per day than ete.amoked by amme mam. (2) Undes th9s ceeditioro the animsL should develop one or mwro of the diseeeee oc pathobgic conditions which in men are associated with cigerette sewl®s- (3) 1T)e atlimals used should dentormtrate a doeereapatme nlation- Arch Enei-en HeaNl~Vol 21, Dee 1970 - - T 0020494 PA - 000469 TIFL 0305392 shil F dog prel gle trnc tet char as t Pmd I trac deli~ betw I az onlam I airth LF Cignn I sea rette. on It' ' inctet cigare ( her to Tet in ehe seven wea 1: died a von: a pulmo larged broneh distent inchl(di atypia epicsi The that be tain ef agarett wntinu method ing the e'~er, tb indiute long pe zure ws Re)imir The i primaril ing cissl
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.r Jf CfGARETPE SMOKING AND DOGS-AUERBACH LT AL ir7.c ol /nrpai.. Lung Tumors in t; Nt Smok.d NmWtr. Cigcrclfn InMUVe Crml[nioltr alveolar tunprwY/l Ma76f (LA) M611a (LA)t M66la(RA)t Maa9e (LA) M69zs(RA) M891p(lA) M8)6a (LA, LD• RA) h6SA (IA.RI) n619 (LA,RA) M1t6 (lM M163(LA,RD) • LeR mal pronahuf. LM6: laft apkal Eransn pron- Mu.. LA6B: etl ap/eN lopp. tA: len Eiauhrqmetle. LD: ri8htapiul Ao ri8ht inVrmWieb. /tl: ri/M Claphr.8- m.tk, RD. } Dep MSJr7, anb MaBL..aeL nl WH<e e.<.n.vly taa•meua CI,III p/pnCnl./ ClrClnUma. i116 nab an in. ruiveprene tbla•.Iwbtartumbr. rr41~'.•> J > .~ ~tl {~ {e or~ `/n ':`00~' ` . dto'. .i6/ (A -tJn('L,f !•! r • :~T ~ i l. 759 r10 2"-Ta0. Imaa/v. bonenipb.MWpr tumar in emoMi/q beg N676a Na haC anqke8 6.129 eigaratts (rpducep fmm x 100). Bot~ Y6gn•On.+r '^w, ca pprtian ot hmor pt tGp anCwing <vn/lu.m tYma m6as. NuGa of tumpr nlb nty in La .np f W M.M enw prominMt nuckqi (reduaA hmnx Jp0). Q RY __.... . y. L ,\: .... ~;,P ,~. _. \J.`~ .~.,r+• T`5 ~ Qa.',r Lr ~r . .,t~j •YL ~•Y• ~ {I~ _ . ,•~J. . ,1,I~ .~ ~,•~;- 0 R, +,1In fJ,~ ` ~.t.> ~U:) ~ ~ Arch Ertniron Hrplth-Yat 81. Dec 1579 .- ~ w TIFL 0305411
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CIGARETTE SdfOXfNG AND DOOS-AVERBACH E•l AL from another. In other instantan, it ap. peared mote likely that two different foei of neoplastic rolls etcae independently. The grossly visible brottehioio-alveolar tn- tnore varied in sia from 1 mm to 3 x 3 x 2 cm. Microscopleally, eaeb tumor was cnm- poeed of numeroua f«i of neoplastic alla together with areaa of nonneoplastic tisue. Small foci of neoplastic cella within a tvmor were nodular, and, to the naked eye, reaem- bled miliay tuberciei They often tended to merge imperceptibly with the surrouatfing parenchyma. The somewhat larger Focti of neoplastic cells were generaily more di8uae, gray. firm, and f1at. The large9f foci wete usually yellow and visibie through the pleura. Norro of the tumora found ia the dogs resembled either lobar poetmmnia in the stage of gray hepetintion or lipid pneumo- nia on gros or mictampic The histologic pietme varied from one tumor to arrother. The neoplastic foci were invariably associated with a bronchiole. The Fig 1.-Tap Nenlnrstlve bmtrMeroahreelar tumor b nanamoldnp dog N904 (relutM erom k let). aMNm. Miee•¢mau vihr n/ pmean et tumor at top .hewing aMM wrlatiun in sin anG seape yf m/eIN (renuteG trem rt iee). s.i^ ~ /~ ~ A q ~ s s r1 J a 1 v1 .I ~ . ~ ~ a ° ~ vi ws i • ~ " )• • ~ • a:u }.A ' S1~'- ~;`~ -~e ~ A ,4. • jte n ?Alu ;s ie ~ ed2 39~°0 ~ e.• i NY OO / S~ ~ ? ~ m~l r '!-~9 Tj - 4' 'a ~' C :In ii.Aft7zo • rns._~% Up _ . _..': .3 A - Arch E..d- XreLA-Vet 22. D.v 1970 Toozas22, Tsete C a.e¢.. wur. ceM: imnv.a : .i+eat• fauaTf ® r TIFL 0305410
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Histopachological findings Tbarerit anrrr. In 3 animals the inrima showed changes: Ttuckening of the intima (3 uaccd animals), inc=a sclerosis (I uatedwimal), aadathavnntosis (1 control). Distinct medial sdecosis uv found in 5 treated aoimalt the norrnal range, when humaa ralues are taken foc comparison. .j summan• of the blood cell counts is given in uhle 4 and 5, them ate no dilferences, eacepc for a small and 3 contcolt, to dfare arrrrHr: Evident medial sclerosis was found in 2 treated animals, the aortas of which were without 1at• degeneari.•e alterations. In 2 treated animals and 4 controls there mas a slight pacchy thickening of the intirna. In two wo onlq the .udaa III staioing was unsigoiflcandc positive for lipid deposition in the intima (I control and 1 rreated uumnl). CoronarJ arrerrer: Only 2 controls showed alterations which resembled medi2l sclerosis. In 13 controls and 9 treated animals pericascular and interstitial :pmphts- hisduc}zic infiltradons of .-acious degree were found. In these sections alreaadons of coronary arteries With respect to fncima prolifention could not be ob• serced. Benal arurin: 10 controls and i«eared animals showed aaeriolosclerosis, occasionally combined with slight arterioselerosis. CereGral arrrria: In 7 controls and 11 treated animals perieascutas round cell infiltration was presenr- OrGer ergaer: ficer sections of most animals (17 controls and TL treated animals) showed sound cell infiltrations in the petiport2l tields; in some animals proliferation of the bile duas and centrolobular h}peraemia could be obsmed. in addition in 3 controls and I tceared animal there n-as a diriuse and ritee vscuolar fany change of the liver. Degenerative alterations of the hepatic vessels could not be seen except for one tase of subendothdial amyloidosis which was also found in the rensl glomerula. Tubular nephrosis was found relatively often (7 controls and 12 treated animals) aith reabsorbed pigment in the tubular epitltelium and with intrarubular calcitiation. In 19 animals ( 11 controls and 8 treated animals) fnrer- stitial round cell inr.ltntions wen observed, somedrna combined .vith the above mentioned tubular nephrosis. The epirhelium of the urinarc bladdex of only 4 conaols wu changed as in estarrhalic cystitis. Striated muscle of 1 conrroi showed inlsimnseular alcfietioa. No remarkable ehaaga were found in the secdons of adrenal glands• panseas, aad iotntiae. t 6 Fie. 5 GISUm [oefent /n aerta aner 20 months. \Vnite nane cnntrols; hatantd em; ereetra Servm enaymr a/Ter 20 montN (meam = ee) Hntyrea ml::ml Nicattnadrratee anlmals amrlar. u6 (n - li) etb cnartlnatu9 cnm;nnterw 31.3 _ 18.8 (n - IB) IA~0.] (n - IB) ntmu aeevamsatut. H.B±6.9 (n . 19) leucne amino peptidaq 182 _ 1.6 (n.19) 'o.eltol atny6res.n.r 6.4 e 7.4 in . 18) alanure tramemmw t0.o _ 2.5 (n . 181 ascartaretranaaannw 12.9-e.i (n - IT) i1ki6ne vneavhat'a' 19.0 _ 13 tn - IB) 61< Taa. 3 - ol Ccnrol animalt w, pe 272 = 118 (n _ 121 °f~ 21.i _ 6.6 6b (n - 12) 0.7690.2 _ (n - 12) i3.2:33.8 (n - 11 Di 21.6 _ 6.a ln _m in - IL u: z 3s DC /n - 121 a fe. 10.4 24 M - tl) fro 18.0 c tA tn - 12) • yni tan. 4 CrythntytA Oloo6 GL[.Nb, nemoelC6ln and eamatoult arter 20 montin (mean.-to) Suela« erynlroeyte cwnt m~0ient 6at mrne Eloe6 nemnetee/n s lao ml n1eeA nluma or ernbec,rtee rm• nematntnt nane8lealn ceeunt af sin ee nLps.ryelrraeyt. vt Ulm muea Bb le t000imm• SicotdteArtatW Control anirnalt anlmats 4.3 = 1.2 4.4 i 0.8 (n-1 Ils = 1 I) ,,.i ~ o~ (n . IT) (n - 12) 90.'f±51.0 B1.0v20.0 x(.3-s: 35~6-ioe 708 _ 21 IT) 26.1 4.4 i00.6 = i732 2917 e'lie) x (n - 1s), (n - I]) Furtherresuln The calcium content of the aorti of the test group is Tab. s - signi6andy inaeased compared with the controls oranuleertn. vertettase aunielnton ana 2o monena(meaeq Table 3 shows the activities of seoersl serum enzymes at the time of sacrifice of the anirnals. dn inaeased activity, of the amrlase, acid phosphatase and cholin- ceteraae and a decrease eE the eti.ity oF lacnte dehydTo- gensse in the trated animals nn be seea. These chan,ges, hoaeva, ate statistically not signifitanc and atc within 1 0020491 I.autocyta :lkotinareataa animan controlan/mau I[u[etyrn eount 2.9 2.9 , IOp) Ger mnM b10n6 ert.sGted tanr a o.s r, u~re etamentt6 21.1 8.8 i>rnane[y,•e Te.{ 6,± tonnoVnllr IA mon9ct p 0 0 eseopniltl - 0 0 hu, mo cig nic to thn this eari dos tmt Fat Th( sigr ben tCSc ndd hut tind aorr canc tatiC .\S / eHtt Z. klin. Chnn. u. klln. Biacaem.; &)asnf. 1970 i Firlr3 Z N TIFL 0305389
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cAnOBSciai l f ~~ ,jovma o the ~ '°~O RE~4YFj ~'y. C/q~17Can 1Fc~ APr 27 ?p <i c.4ssoc~atiaa Inc. \~.\sF.~e<s.~~ . . culatlon '~ VOLUME XLI • NUMBER 4• APRIL 1970 SUPPLEMENT NIIMBER I CORONARY HEART DISEASE IN SEVEN COUNTRIES dnce! Keys, Ph.D. Editor
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:w. CIGARETTE SMOKING AND DOOS-AUERBACH ET .4L 757 TabM -Numbv W Dcqa in WWcA One pr M6re Tvmon (NonMreai.e ar li.reare) Were faund and Ne Number ot Loon /e WMI7l tMe er More Such Tumors Were Found Nonam<bry Giltlnlip. KunlinM. NCnLRY. NCn/Jlv, Group N Group G Group t Gra.p H Grwp b Oppwnl nCis6b.fenGeyel6 Np. ut ep ... . 2 2 12 12 NO, wit eu01e1. 0 2 7 a - Ne.pll b.. ... 1• 14 a. ea No. n+t tumor. .. 0 3 13 6 Opgs kill .e.r d.y 915 Na e/ n6a 9 l0 10 12 ... IIO.wN tumar. 2. 4 5 12 ... %wltb mprr 23.6 10.0 50.0 100.0 . Ne. ol l b4e 56 70 ]0 a4 ... Na.it lumary 2 4 9 22 ... %MIM lunpn 3.6 5.3 12.9 26.2 tot.I:Ak ryupN,F, tlndMdeas No. M ga a 12 l2 24 ... No.Nli tVmCrs 2 4 7 19 ... %wiM umor. 25.0 33.3 993 79.2 Ns of b.. 36 64 e4 1" ... Na.n t.mprs 2 4 ' l2 35 ... %rith mwk 3.6 4.e 1" - 20.9 ... • SgVr Cmin.d becM/M no rroup n Cags w.re kilbd. prim tutnor with metastasea. The term years of age at the time of death and the invasio as used hen, means penetratiun of oldest dog (H977s), was 5.4 years aid; the a lurno into the uaderlying strcraa with meart age at death of the 12 dogs with deetru of the alveolar ardtitectuze and invasive tumors was 4.9 yeetam to of rnnfluent tumor masses. AIl the Detailed Desoription of Bronehiofwdvecler iavasiv tumors had squamous celf foeL Twoors.-Many ot the broocttiolo•alveoler They f 1 into three categorfee aaording to tunma lisied in TaNea 1 to 3 were found by degrse t pleural involvement "' microscopie rather t[nn by grau e3amina- . Ten gg had invaaive broncltiolaalveolar tion. In other instancee maseea were found tumors hich did not extend to the pieurafiat by grvss eramination. Miemsmpic ax- (Table and Fig 2). fhte dog,.H848a, had amination of the gross memea revealed sonte an in "w bronchiolo4iveolar tumor e:• to be areae of organizing brondmpnetunonie tending lo the plettrq with neoplaetic cells but the majority were tumors. The word entangl in the eleWO fibers at the pleulo• tumer applies only to lesions in which there pulmon jtmetion (Fig 3). Four dogs were foei of neoplastic eelb. (H7b3. H86o4 and H89:b) hed in- In son» dogs, as many in 20 tumors were vaaiw 'oloalvenlar tumors extending found in the seme lobe, sufficiently eeparate into the pieurn beyond the pleuropulmonary to suggest that eeeh was independent. Eactl juncti (Fig 4). Some had eeveral invasive separate tumor wae multio.ntric in the sanw tumors Table3). that aome foa of reoplastic cells wete sepa- The rat inve6ive tumor was found in a rated, or partially separated, from other loci dog (h 6) that died on day 626 after hav- by atw of nonneoplastic tissue. The rela• ing s ked 3,925 clgarettes. No invasive tionship among the various neopiastfe foei tumor w s found in 15 dogs of groups H and within . the same tumor mnae was often un- h which died before day 6_6. The youngest certain. Irt many instattrat it appeared that dog wlt an invesive tumor (H7b3) was 3.8 one focus originated by direct extension Arch Enuiron He61th--Vol 21, Dre 1970 TIFL 0305409
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~InOfficaal ` ,~EpICA( !~ Journaloffhe~ ~tnET]CdA~Eflff , ~o ~ ° > ~dvE•~ ,; C. RW 27 7p ~ c~+atron lrtc. VOLUME XLI • NUMBER 4• APRIL 1970 SUPPLEMENT NUMBER l CORONARY HEART DISEASE 1N SEVEN COUNTRIES Anoei %eya, Ph.D. : t. EWtor,'
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t 762 ClCARHTTE SMOKING AND DOCS-AUERBACN ET AL '9 1• Q . LI.. ? j i V s %'t, ';, - '= ~ i~ : d, ~ ' A,'D~ 1 1 . ~ 'YN ~~ .~~ ! r s ,,.; s d , y!; ToP BnnC~ a/ ieh aO~W lobe rron<nu\ 1nm ooy AW)a tlut IW emaka6 6.338 ei0 reltb 1t~ordn9 uM invaaien intn undarlping attCma (tMYUU trom x 2W). Battam. Xiglparar Na of same tumor enowiny muitide nn9an4W; imaaas ~1 tna uneuty/n9 ttroma (IaGUUd x S00). Ry'. .., ~r Q 1 . ; s J . ., )i} '/~' w ~ _ ' .. . _. b . . ~ * ~ I~... s . Arch Erwiron Nedth-Yo[?l. Drc 1970 70020516 f TIFL 0305414 ~-
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I~ARETTE SMOXING AND DOGS-HAMMOND ET AL 1 751 I w.o ao urw.: a:wa F: urou. t: uaua W IFn• FM1T[IFTp MC/iRre M9q,Trn I N/oYIA tWt.O t Fl9 a.--GwCh .lip,.inp One.nt d sacNma wiM praG 2 yabliM ailtaetumnta b a/wWw spb In Coes o/ qmupa N, F, L ana N MK w.nt ki!IN ahar 875 Caya. a.r oa~NYGr w aF~ Cnqtr t: a+ou. r: -~p q /NTw ns nLTq aw.w ~~ Fl9 10.-erapn ' parNnt 91 ltetk+r9 wBa prad. 2 er d a d 9M.a in de9a of 9rap N. F. L and N w.n i1eW anr 676 Nys. no paddiloa a to ai.eoLr aepN, normal thidarw of ar6eFiohr wdl9, and no gceeter pleunl t' 'dmes th6e that found in many sections the nonsmotring dogs, Sections f7om F380 and F954 did rnt differ much frem thoee of the two dop men- tioned abova. from dop L347 and L812 were about the same exwpt that p®d- lihe attadwrents (erad. 1 and a fev grade 2) were found in atl sections ftrun these two dogs. Table 5 shotq th6 peroenWge distribution Fq p~.p/i rha..i.9 ~l a/ Yctlana w{p 2104119 1 nr 2 tnicMnm q wa/N of ubrMan In Oa9s 9t 9:99pa N, F. t. an0 H tNK w9n W/W abr 977 6.R of aea,iiom by gnde of each type of finding in six group H and 8 group h dop which died betwe9n days 37 and 499, a9 well as in the six group H and six group h dogs which died batween days 500 and $73 and the 12 group H dop killed betwKen days 878 and 899. In gmup H and group h dop, Pmdtes+ion co- curred in the degree of each of the five typee of histopathobPic dnnp• In both H and h dopr graeter chaeges were found tn sections fmm dop dying between days 500 end 875 than in thw dying between days 57 and 499; the greatest changes wem fouod in saa ti9m f7om group H dop killed b9tween days 875 and 899. comma& The oriiin.l pfsn wn to obtaiL dop 9617 doae to the a®» .{s and we7aht and divfde ttwo into tour gtoupe: N. P, L, and H. Groups N, F, and L weta ta be of equal siae and group H was to be much larger. Atl swr9iving dogs of gtoups N. F, and L, and a rsrtdam sample of group H dop wera to be kflfed when helf of those in any one gtoup had died. Half the tetntinutg tawp H dogs wen then to be taken off smoldog and the r..ted.r were to mntmtte stmlung until mo9t had died. The r.bov. plan wae modified when we w9le unable to obtain dop very doe6 to the ArnS En.Len NaltA-Vof 71, Dee 1970 - TIFL 0305403
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itnouuon En turo veiop a identi• Belgium nts and' ect of political e repre• ,ork ef-i 1hup risr in oil vastly tnagnified of inflation and which it affects ments of society. It Is beginnin= stood that the structure an whic d Den- Goverrt• ly week France mly in intense runtled resident d Chan- f West iccused; ;nce, of leader- policy Market, perhaps olitically e vision• ithout a ons on ,ilt seem ielves a id large, )st other planning had bee been distorted an e. e,uc cn~., pNccy hau; he problere:,• he wsy arious seg. i be under• hole prfte econo?nic based has that trade and therefore employment are likely to be twi kilter as a result. The political in all the affect wwa.e rnn >n C : ,~r~ Catholie Acc ( - by C. F18Eg of the 16th Century-need not A joint cor~ntission of Unitedilon;er be a "barrier to recon•~n Ic of their churches ciliatEOn" . States Roman Catholic and Lutheran theologians issued a' S:atement' In a 5.000-word "Common,s the scholars en- o study yesterday declaring that;vis;oned a time when Lu-~o papal primacy-a major issue thcran and Catholic churches Contiaued on lage17, Colttnm 1'in the Protestant Reformation,,would be part of a single ~ "larger communion" - autono- jmous but linked by common orkers Still Face recagnitian of the Pope in Rome as a visible svmbol of Health Peril Despite Lawl The recent disc liver cancer a chloride workers renewed attentio ment, labor, i medicine on the By JANE E. BRODY very of fatal each day ong vinyl diseases. 1rorn c,yttsh site by rescue workers from occupational has focused The General Accounting 0f- of govern- fice acknowledges that there dustry and has not been nearly enough housands of money and staff allocated to and as yet make a dent in the vast prob- th hazards tem of occupational health. In that face 60 mil+ion working known, suspected unsuspected hea al prob- Americans. tined the Despite the p I of gov-1years ago of the i Europe. Safety and Health nflexibil-i every American partisan+work without ration of threats to life an s appear Ss of sil- overwhelming workers are not E capitallby the law's pr 'lack of this pr dommon ldreds ot .vorke ssage three Occupationah, Act, granting he right to job-induced health, the ajority of et protected visions. For tection, hun- a are dyins addition, fundamental scien- tific knowledge is lacking upon which to base remedial actions, and without more funds the necessary research is not forth- coming. Historically, occupational health has been a low-priority item for both government and medicine. Yet, each year one of every Continued on Page :f, Column 1 A their underlying unity. The statement, whose formal title is "Ministry and the Church Universal: Differing Excerpts from conclusions are printed on Page 25. Attitudes Toward Papal Pri- macy." was adopted by the 26-member Lutheran-Roman Catholic Consultation in the United States. The commission. which com- prises 13 Roman Catholics and 13 Lutherans, was appointed in 1965 by the National Cotn- mittee of the Lutheran World Federation and the Committee for Ecumenical and Inter- religious Affairs of the National Conference of Catholic Bish- ops. The Lutheran delegation includes representatives of all major branches of Lutheranism in this country. TIFL 0305419.001
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lg? >~ie.a{brio, V. Londong, W. r ondong, GNtobeh, Rmtpiik. Scirauer, and Immich: \7eatine and vte.imdrrocu Bh. Pxking: I0?. dicthylsuaio.re on ebtomosorb W, A0.'- D\1CS, 90 to 100mesh. Tempentum: inicsion point: 310, , dateceur 3t10', ovcn lprngraauuated): 110-190', 2' per ow:ute, reJ(minvq, upptr limit 20 minvn. Canic gaa: nitrogm 40 :\'ineine nn.nariw wss pedcmied by pa•chmtrotogephF artord• bsg to a mehod published nrli¢ by the ptvmc luehcn (32). FinAr en164: Ser[[m enzytnea: aspuvee snos+mmaae (EC 26.1.2) (I:cu[ax (33)). alanina «amaotenae (EC 26.1.2) (\C'aoe• rzasct and LnDes (34)), twditol debrdrogenafe (forbirof debidto- gmur, EC 1.1.1.14) (Hotsaa, H.uv md Sn~ou (35)), leurm aminepeptidee. (EC 3.6.1.1) (N.eu, Ksvo and Sexauer (36)), aamTlaaa (EC 3.212) (Soroan (37)), acid phoaphatae (EC 3.1.3.2) (Fuwu.w (3g)), alkaline phoaphaau (EC 3.1.3.1) (Ba- ser,1qmtr and Beooa (39)), lwate debydrogeesu (EC 1.1,1.27) (Wtonawxsu and L.D.2 (10). Hewerolupial rJerbw ww6eJr. Etythtoa7ne•, leucoelee- and tlveetn bo.~u<uuntfog vith <ounting chambrr. ffemogl.obin as cfan• bemigfubin Esci[mcion of K•, \a`, and Ca-' in the cmum n'ith Bame photoeweer, uren with uteas.. Blood cugae enzymuiesllr mith the gluwt. o.idaae/peroaidavmetbad. bFrvm pNteins dec- wphontidlY. Cakium e¢imation in aonie tissw aeeotding to Fnm and FLue (41). At the md of the eaperimmt the astimis xen ana[beswd by a blos en the euek and waw bled from rhe A. nneis. The orgw to be inrexigatsd .ae either remored and deep Gotei umil ptoeetsing, or a Fo"r•Sesa,tr earras me ptepated. For the mirtorion of the olchun contetse and anof tbe lipopeetein lipafe of aottie tbNe, eaenfy the sune pan of the .caasl a aa a(vajs uaed Sututue" werbdr: 7Te girm pteblem include the comparison of tso netmmn, namely "nicotine" spd'•coetrol". 3fonoeee the ctfevs of the fxron •'age" and "setum" bd to be invotigued. thaelore the wllti of rarimm has bem chosm as an appto- prute stariuial modeL The aoalysis of neisstee requires mump tioas u follon: (I) hor[naLLy diatributed dan (11) Homosedsaaidq (IIi) Balante of srcup (IV) Iudepmdcccy d date Aasumptions (1) and (ff) hare beee ful9led b7 rnnefonoacion of tbe original daes. The balsnee of goonps hea been produced by uFe of nndout numbn>m fod.pendeew Ms hem aimed hr tbc ' tsethod of linmr conmse. The dfsm of tteatmsno han been comidand like fse, [he aefem of "sge" aad "spum" a. esndem. TLe p.aunu[ion of eeeW[s of the amdysb ol .aaiance teswuncr a ditplaF of sutd.rd dee'stiona 5etne of the data art ptefented oNy ia tablea ~i[h,wt the uec oF terrprocedura Ia tbeae tabin the anndard derutin.u hna bevt compoted. in eseimrtiun with theea panmt..n ~ac not _oe,. fo,med; beeause af thc ilight deeiariops of the nlun the d's- uibuelone of the nrigimllan ha.e nue been cheel<d H'mlyir.l vndvL; The aorn, main aeteriy, hett, I[id'e., liren srrhrod ir%ncle, pnneteoa, intntine, snd bnyt aerc in•eseiga[ed mic[oxopidll.. Frnne wme of the anitrola the ad[emL and the urinary badder ~ate tlso inresrigued. Aher formalin nnnnn (10%) panifin rcaions uem uaiaed n'ith hactntosvlia-eane_ F[esulo Body weight Hoth groups showed a normal dn-dopment of body weight with no di$erence bertceen the controls and t.he nieotine-treated animals. Ac the end of the experiment the mnn weight of the controb was 4.04 and that of the nicotitsetrnted asumsls 4?21:g. Nicotine concentration The blood of animals created with nicotine in the same manner as sha esperimcnta) group shomed in the period from 15 to 60 minutes after uptake of the whole dose 0.2 to 0.03 pg aicocioefod blood. A rough balance after estinucon oE nir:otiae in faccc aad urioe showed that praetiafly the whole ssnounr adrnioistcred had been resorbed and tttetsbolized. From the smmsch content, about SO0/* were resorbed after 13 minutes. in snml organs, brain, heattt, uiivary gland, adrecals, and aorta traas of nicotine could still be detected after 9 hours. This observed resnrption of aicodne into depors, and especially into the walls of the blood ressels is in accordance with fadings of other authors (42). Fat metabolisnt Total eholesterol, phospharidet and esterifed hecr acids in the biood rise toward the middle of the lifetime of the animals and begin to fall romards the end of the esperimene (6g. 1). ]3ecause the cen- centmion of free cholesterol does nor change, the rise uf rotal cholesterol mussr be attributed eu a change ia the kvel of cholesterol esters. With regard to age thne r}unges ace staeisdally sigsfificant: (P - 0.01). A sigtti. P To/ef GylCr TFhdOeJetMat lreeOddupl frhnRN PMapSetiaW feNy .Mldi p n p p Ii / sr 0 R ] t IG e II M ! 2 tJ 7 R 20 I R ID Fte- I eCnunlnltea W npfee in te[um atur g, 12 ene 10 nMetht Wlete bene mntrae hatcheC ban: tr4ted ' (J(,""()98.9 Free ieW ruia/ e'rn e?ier Poaq ~N[I TIFL 0305387 zldfe.amr-e.f[B=.Bi,rb.nr.lt.7ahrg.t9ra(xda3 %~ib
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befn, V. Loodnng, R'. Londnng, G[umb.ch, Asmplik, Schauer, u+d Immicb: \icaine aad artcrio.daoria !9j J Ta4. 6 Compealtion af serum prateim 4ur a0 montha (means [ne nnR) Alaumin r11..: rM~° cmm~m raL.-y q/100 n,1 Ya,al 1 ,100 m1 AUp (n i } 13) b 6 10 16 1 4 1 <antro t - sp1t tt L 4p 7-12 ID-20 0.83--ISi . e.1--6.7 nKOth,a[YtN ad imals tn - 17) s0 6 r 11 16 1 5.9 - 3-M s-77 11-27 0da-1at e.9-7.1 incrnse in seg ented cells in the nicotine-ttated group. Table 6 gfs•es t e compositioa of the serum proteins. The total protein i lower in the eest group, obviously dependent on a decrease of the globulins. The concenm- ions of elear 't:es, uca, and blood sugar of the test group rescmbl, chose of the controls (cable 7). 'dl tF.ese findio¢s hare, csuse of the slight deviations, as already mentioned, no been statistically toted. Therefoce anr kind of genera idon seems to be impossible. ran. 7 elKtrntyue. u.e# and hlood roru afeer x0 mnntb (rneaY p fn) bbaC compenen I Discussion \ku,ina-trearee Contral areup e.9 ~ 0.4 (n 7 In) rn . •1 1 143 _ 4.2 1J1 = .6 1 . 16) (n-IU 1: e0.7 4.3 _ 0.7 (n . 16) tn - 121 2a t = tl.e 2ad_-1. um 9 - ss) =~x In - IA 207 a 96 (n . le) (n . Im :\[iroiim dpiogs rtd r~rtnrtrratipx Depending on merhodiol difficultics, there exist vets few obscrntfo on the amounr of nicotine absorbed from tobacco moke by the human organism. From snimal esperi enrs and from tlimone estfmations in -human blood •e aa conclude thu an arerage of not more chan I g•nicotine may be ruorbed from one dgarerte br i ing (43). Under this assumption the nicotine dose u ed in this esperimenc would cocreapond to the dose a smoker is inhaling who emokn more than 100 dgar daily. .4ilrFtough the dosage used in this e:eparim is deflnfdvelr lower than in most culier ins•estig tfoos, it should be remembered that this dose is higher than an be ezperxed evea by heavv smokers. te] _ 4.4 1 Fat nM4bL~m The composi*n of blood fac shovn a stadstially slgmaant alte aon accoratng to age, oln no aurereoce bcta•een conr and oieodne teated aofmals. Tne results with r rd to the concentration of free farty • Imunn : acids in sem ue in fact mtisdally aot si¢nifianr, buc seem to be worth repadng, beause of the nnding that t e activity of the lipoprotein lipase of .aie riasue = ehe nieedne-ernend ani[nale is siqrilff- cindy elevated and these conditions may be an adap- tation to - sed lipoivice activity. As mentioned a4esdr, nicotine has a marked lipolytic .' c9ect via rdeas of arecholamines. This has been proved i in our ou•n experiments (44) and br KFa.sN6Aes1 aod coworkers (9). This Eaa caa e.plain the high concentn- don of free fatty acds in the scrum and in orSans, as well ae the decrease of the coneencration oi neutral Eu, espe,aaflc in the liver. \icotine t.4erefom does nor promote lipoidosis, on the coneracr, it relasa free httv acids from tsaglrecrides, according to its above mentioned metabolic actions. These results are in accordance wich hndings of Cc=~'~s.ex.sst and Fxsn~o (45), who showed that the tneat from nicotine treated pigs is prorein-rich and poor in fat. For the (irsc tirnq we were able to show an increased activity of the Upopcotein lipasee in heart and aorra under the influence of nicotine. This result seetns to be an impomnc point for further iavesrigation. The acti.ity of this enn•me in the blood of the nicotine- treated anirnals could not be estimated, because of the vcn• low activity of the etrs}-me if not stimulated by hepatia Heparinindon could net be performed because of the possible influence of hepuin on other parameters to be masured. It has been assumed, d•ut a chronieallv elevated leiz! of free fatty acids in the blood may Lead to an elevated level of cholesterol via the $-osdation of free fattc acids and subsequene disposition of C-2 compounds for cholesterol smthesis. Our results do not favor this theory. -Oar results are in accordance with 6ndings of Gta aJ.+aNasoN (46), who, after nicotine adntinistratfon te dogs, found basically the same results especlallr with reaud to the eolscesttnooa of fat metabolites in serum and organs. He moreover found an inhibition of cholesterol synthesis by nicodne and a sisqltifiom pro- longadon of the half life of administered cholesrcol in the nicotine treated aniesals- Our results ttnv esplain the surprising results of othec authors, mentioned in the inttoduction, that the level of aiglycerides in the blood is decreased in smoL-ea in long time and acute aperfinents. The increase of ehe scn.ity of Upoprotein lipue may be the explanation of ths phenomcnon. Etls6p pf, nrrrrfax6rafs Our results show, that nicotine alone does nor produce a Upoidosis even aher prolonged adttlinistntion to .nimels, who rend ro.poneaneousdn-elopeneet cf aneeie. sclet.osis of the main atteries. On the contrary, aicotine aco IipolytEcaUs' in a¢ordancc to iu known pharn»- cological effea. ZratpLEvn and coworkers (47) showed in rabbia an incremed lipolytic activity in senfc dssue T 0020492,
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Program Ekhfy-seventh Annuat?(eefing E ASSOCIATION OF AMERICAN PHYSICIANS Pennsylvania Room, Hoddon Hall Atlantic City, Netv Jersey Tuesday, Muy 7, 1974 MORNING SESSION 9:00 A.St. Genent quxines~% Nleelin89:00 A.M. e+idential Addrt.+ 11•'renae E. Yl,ung cieutifie Sestion iawxce E. Youn;.Praldin: I. HETEROGi!. F.ITY OI' INSULIN RESPONSES IN t.1TENT DI OELES. S. S. FajmuJ. C.I'Icyd.Jr,• C. t. Taytond S. Pek• Aao Aebot, blichipn. - peg S67A 2. >(INERAL A 'D *,"ITROGPN M1(ETABOLIC STUD0. IF.S ON' SKY .AII ORBITAL SPAnn FUGtfiS. G. 1). tvhnMn. I Lot-:J,' :. HciJ,• P. RandqU,• \/. Mbitt'<.• %1 Srddh and C. (s:acb-{tontoon,• Sethesda landl SepW+M4 CalifOntie: and . Y.omton. Tr. ' pse S70A ,_ ABYORafAL THYROID FtIl9CTION AND TAE - RESPOSSF:'1 IDUIDF:3LNt75TICFInROSIS I+. nzisi.• D. If: d.y.• .1. Va¢nnk'u,• G. Pnrtnay,• II. Shuz.hman.• S. (n--ber. aod L Blaweman.• ee.oon, Aluv.huana snd San Franrieea. CaBfornnv . paRf 556A 6. F:~PRESSIM OF Tt(F FAMILI.V nYPIAiC71f} I,I'\I I Xlt1.P Il.t CIPNF IN III't'P.RfI%YU(rl7iS: )i(11/L1 I Ult r1 IwMINaNI' UI3111tU1'.R IN AIAN. J. 1.. G..IJJ. u•.n.l M. S. Hru..n• llnle. 1, Il_ lV. S.:IdInL I}Ao . Tccvt poye 55VA 5. 6LO61\ NPSSfi\OER RIRONCCLlIC ACID CDN- 'fE::T DURING LRYTNROID CELL DIFFEREN• TIA71OJl. F. Ram'vee-• R-Camb:ne,• 1. Banlu.` R. A. RiRand. P. A. Maaka" and A. Bank; Nea Ycrk. Ne.v Ynrk. paqe 561A 6. PL.iTELET COAGU(ANT AC[IVITIES AND VENOUS THROMBOSIS AFTER HIP SLRCERY. P. N. N31.b• (•alr.by S. Sherty), Pniladetpnia, Pm+. sylvmia. pnte 163A 7. IMMUNOLOGIC PARAMETERS FOR MONITOR. ING IA(.NUNOTfiFRAPY WITHT'UNOR SPECIFIC TRANSf'•F.R FACTOR. A. S. LeNn,• V. S. 6ym.• H. H. FodeMsr, and 1. E. wybran," San Fnnciaco, Catifolnie. pnp3'704 " 8. AGF..ASSOCATED CHANGES OF AN A1IYLOID ' REUTFD SYRU)1 COMPONENT. C 1. RorntaaM , and L•. C.. Franklia. Nea York. New York. pefe 5eR1 9. PRESENCE AND ROLE OF LYSOZYM2 IN HU- AIAN OSTEOARTttRITSC CARTILAGE. 0. 5. Howel(. R. D. Ntmn.• 1. C. Plta.• and S Kuet- tner,' .%temi, FIurida, and C11io8o.IEinoia. t~ JRJd lu._CIIURPTI'C s>,101:(NG ANU LQNG CAN('FR: 'rilb: PROOLI!NS tfR "DFTECTION etA$" IN F31DF?110LUGIC RATF.3 OF D(SBASE .A-R. Feina:.in ~n6 (:. K. LL Jlt • Nwr Harm. Cnnneti~. ' p.xelJlA T00::0523 177 / TIFL 0305422 _I
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CANCER MORTALITY FOR SELECTED SITES IN 24 COUNTRIES No. 5 (1961-1965) BY Miteuo SF.C1, Minoru HURIHAHA and 1Yuneaki MATBUYAMA' IN COLLAH(A2ATION W]TH Mureka [TO, YarLi NAGANU, Tukoku ARAYA - anr/ tkulr NASH[HARA DEPARTMENT OP i'UBLIC HEALTH TOHOKU UNIVERSITY SCHOOL OF MEDICINE SHNUAI, JAPAN August 196' PA - 000478 TIFL 0305440
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CfGARETTE SS(ORIVG AND DOOS-AUERBACK £T AL bronchiole was completely or almost com- pletely surz ounded by the focus, often form- ing a sphe In some instances the tumor extanded ward the pleura in a linear fash- ion and th pleura overlying the focus was thickened. e close relationship between bronchiole nd surrounding tumor was ap- parent by e number of openings in the communiea ions between the bronchiolar Iu- men and t surrounding acini in the tumor (I,atnbert's canals)? In some areas neopleetfc cells were ar- ranged as a ini while in other aress, partfcu- larly in th periphery, there was a papOlary formation. e epithelial cells of suchacini and papil • losmltiwn varied from cuL•oid- at to col r in shape. In the most be- nign-appea ing forms, there was a single tvw of cubo dal cells. The nuclei were slight- ly enlarged d the cytoplasm increased and paler than uaL The beonchiole in the cen• ter of the or often had the same type of epithelial lls as those present in the acini, particulart at the site of Lambeet'e canale. The snom in such areas was dense and f 761 cnmpased of variable amounts of fibrous connective tissue among which were itrands of smooth muscle bundles. There were sud- den or gradual tnnsitiona from the tumor to normal parenchyma. The tumnr cells were often present on the adjacent supporting alveolar septa In other tumors these was an increase in the number of cells with an alteration of their cytologic characteristics. The luroens of the aduu in the tumor became small from an increase in the number of rowi of cells The cells were often arranged in sheata The tendency toward a squatrous character was greeter when papillary formatioro were pres- ent The nuclei were larger and omtained prominent nucleoli. Ocasionally, mitotic Ngures were preeent fixtensive peribrsmchi- olar fibrosis occurred often. In other instances there was greater varia- tian in the s'vr, shape, and staining rlurac- ter of the nuclei. Nucleoli were more promi- nent and mitotic flgurn relatively frequent. 59tamous changes with we{ldefined inter- cellular brfdges were extensive. The nuclei i'p 5.-LSh maln bronchus fran doe HaaS, that hse smoWd 6.210 elOS• rsns shaWne urtj imasian inro undu/yine tinue pnev) (nunamsylin,wain, x 160). Arch Environ Health-Vol ?l. Dte 1970 TIFL 0305413
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CIGARE7TE SB(OK1NC AND DOCS-HArtLNOND YT AL the smoke thc by reducing tar and nlcotiee rnntent So far we know, it retnovee only a small proport' n of the gasea from the smoke- Thus it seeme that the quantitatiwly different effect on the lung parenrhyt7u of dogs of smoke from SEfer-tip and nonAltsr cigarettes must have been due mainly if not entirely to the 1iRerenm in the tar andlor nicotine conte of the smoke. We believe that Hndinga ' this experiment provide strong support or the opinion expressed by a group of im igatora who reviewed the question at the request at the Surgeon Gen, ewhr: "The reponderana of scielti8e 753 evidence strongly suggasts that the lower the 'tad and nicotine content of cigarette smoke, the ltag harmful are the effects." The filter used in this expariment reduced both tar and nicotine in the smoke. Since both were redursd, we have no vray of ktqw- ing whether it wae reduction in tar, in nico- tine, or the combitxd reduction which accounted fa 6nding lesa pulmonary emphy- setna and fibrosia in the lungs of filter-tip dgarette smoking dogs than frr the lungs of nonfilter cigarette smoking dogs. '17ue study wts auppqrted in pert by .,rtmcp gnnt ttota the Ameeieut Cancer Sueiaty. Ine Refer.ete 1. Hammwd - smekiea ia reWbe to mortd'w ty aad owrbidity Findlnp in ant 34 moetn. of fcllnw-up is a P pettiv, study thebd io 1999. J Not Canrrr Inet 3 :118I-118a, 1961 S. Hammotd C: Smokiua in rAtioa to the d.ath retm an million men end woma Not Conce, lvt Mon tAtfl-'JOt 19ai 3. Haba HA: e Dete u.dy of atmkbts aad mordlity atatos U• S. vtbnnw Aeport on 8% ynes of obama ' Not Gnto lart Monop 19:1- 125, 196a 6.Iblt R He A8: !.teAslity la tatetiee te amek4ns: Tea y« abaervettone of eAtLh danon. Ertt Sltd J 1:1 1410. 1'JBL S Auairah 0. Stout AP, Hammord EC, et aL• Smokioj habiU .p is .olation to pulmesary chaase: Ruptun of avwl.r sptuma. AOroeb and thickentns of we of small arteeim and aMtioiee. Nrm Lnr J Ntd 10t9•l0et, tael 6. AuaberL q Stout AP. Hammatd EC. .t al: ClungM in tptthttit® ia n4tlee to ttp4 tott. xwldqr ud is n6fiee tn lueg ae:ter. Nro Ent d Mtd 78eM&287. 198L 7. Rahq EE: Evolution of cirenlN tmakitar t.eheia ia dqe. l.t SuH td:~W,1ea6 e. AumMre 0, Haomtnnd EC, $kms D, .t eL• Empbyxme podot.d ia dora by cisvate rmohioa JAMA 11eQf13M. 1&17. . 9. Auerbech O. Hammend EQ HLmu A at aL• HLtoMaie th.neee io bnnthial hdns of tiPtrttt tmoluar daar. Caartr ZO:R065.EOG6, 1967. 10. 6h.a WO, Kinoea D: An e9eetlv. syateeo end peoedure rer, eiror.Re tmoldna by doe. J 5urr E.M e:Ser-895, 18ee. IL Aunh.ch 0, tfemmmd EC, Kirman D. K al: Edaeta of cinutM amukina on doxs II. Pulmowy awpl..me, Areh £n>iten HraitA SWn476a. 1910. 12 Tr.dmnay of WilNam Sttaart. bf. D.. Sun reen CrMAI. Public Htdth Seroier: Xwnear Be ler. th. Con.umtr Suteemm(1tw n) the CanmiMer wt Commtnr. US 6enaw, 90th CoosrwS 8rat su- ame, Aus u.1967. . Ao6R[ElIOM CON7HOt TO IN7[tuCTUat. BOUNTY Profeseer ttMz mdntamu ttat the history of the id.ndert-who ehaqed frma tatw n3ats to ami fratatad people in a fevo s.neraaee.-.demonetsM man'e abiI- ity te ooa 1 his agpeaoon. '2[ the fearsume onaibe6 could chanp rapidly, ona they no needad te fwr their tNlow men. when in fact tetair dicritm wae no lontler eat or be ea en, them is a ohanoe. at Itaat that v tee may learn to enjoy the bounty available to not that frnm a ts.ming otean or a ptoduceve wirnnia aoil, but frotn our teemin and productive minda"-Hrupp 0. miw of Lidr T: The penenr His Denrlopmr Thruut/rout the Life Cycle. Saturday Rtoiru, Nov 16, 1966, pp 48-49. uy TIFL 0305405
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t* Cemet may lead M ier toxicil Coses - levei deter 'iC rea[iiM trVeH. smla ,roeo;e +n ranpe fral sma~~er epor ~nUg1d mscwn ' nonsu ;Arvxt ie mea p cline 6. cy..n :obralbn ieU «u eE eQ , easaE f 3ie beeM1 arca ra ms in .v .~y a Case Re Medical Arts and Le ers Edito 'als ILSet the exam PA - 00047 Scien Aiti Clinicopatho Electrocardiogr Anesthesio 0 AUGUST 1 / 1967 Lack of Correlation Between Antemortem and Poet- mortem Diagnoses . . . . . . . . . . Prutting 2081 Amniotic Fluid Embolism . . . . . . . . . . Philip 2085 Lung Scanning in Pulmonary Diseases . . . Touf and Wagner 2089 Arterial Hypotension as Temporary Means to Control Catastrophic Elevation of Cerebral Venous Pres- sure . . . . . . Owens and Passalis 2096 Community Cancer Demonstration Project Grants . . . Handy 2100 Recent Onset of Pruritis, Weight Loss, and Dark- Colored Urine . . . . . . . Lenox Hill Hospital 2103 Electrocardiograms of the Month. . Rubin and Frieden 2114 Severe Gastrointestinal Distention During Nitrous Oxide-Oaygen Anesthesia 2117 Pernicious Anemia, Polycythemia Vera, and Acute Myelogenous Leukemia in Same Patient . . Roener, Rubeberg, and A2ta 2119 Adult Hemophilus InBuenzae Meningitis . . Joffe and Diamond 2125 Pregnancy with Diabetes Mellitus and Addison's Dis- ease . . Strickland and Sode 2127 Prolonged Survival in Abdominal Lymphosarcoma ' . Tobin and Argano 2132 Intussusception Due to Pyogenic Granuloma of Ileum . Payson, Karpas, and Exelby 2135 Pulmonary Alveolar Proteinosis . Lynton and EorreUt 2139 Conan Doyle's Dying Detective . . . . . . Ober 2141 Physician heal thyself; Results of health screening es- aminations among body of physicians and em- ployees 2077 ,, Complete TaEle of Contents: pagas 2048, 2d90 p!e-use seat belts! ss;ss r, 4s1l 1:Ea4U 'ST/~ / x.ta,zcjjl TIFL 0305424 ~3a$a F;i 3G ~3Sssan~ufl
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TRANSCRIPT OF FEHS CONF'cR_°:dC° SU8GE0: GENERAL LllTE[F.4 L. TERP.Y _ On Rcleasa Of "S?[OFING M\D HEALTH" REPORT OF T3[EADVISORY C0.PffTTEE TO Tr.E SURGEON GECIEP.AL . OF THE U.S. PUBLIC $E4LTH SERVICE January 11, 1964 WASHIHCTON, D.C. T00ti0532 TIFL 0305445
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42 Prn(. !i(rin: Perhaps 7rou would like to com• ment on ihis, Dr. WynderT Dr. Wyndrr: Actually, all I have to my I had planned to say tomorrow because all the points which Prof. Drucktey covered we planned te cover in our presentauon tomerrow. I am de. lighted to xe thu the same type of ptogam that we are carty+ng on in the United Statei is being ca[ried on by Dr. Druekrey in Germany on a diffeeent animal system, and I believe that these studies are important enough that diffa rent investigators throughout the world nut only duplicate these studies but wark an difLa rent animal lystemt. Certainly these studim show that mbacco smo4, is carcino{enie not only to mice but aho m tatt. We will ditcu» tomorrow how we think the careinogenic etfett can be elphined q1 a combhtauon of initiating carcinogens and ptontating rubstances. One of the things we do Imow, of coune, is that initiatu ing subwneP in vary minute tonemerationr, s.e, one mtcregnm, can produce cancer s.hen followed up by ptvawting substances. For ex• ample. it has recently been shown that as litde as one mittcgram of D.NBA aeted as an initiating eateiougen. And our turmet belief is that thir ia how the polyryclie hy drecarbona in mbareo sotoke act, batauee we have shown that if we can remove the hydte- cubon fraction from tahauo smoke conden• sate it lous more than 90 per tent of its cardnogenk atdvity. I,et me nra that we b~ ]ieva that it !a only acting at an inldatfnf eu. cinogen. In a recenr study that Dr. 8ofttnamt and I publ3thed we pointed aut that, by itself, this fnedoa could rxeaunt for not mure dun 3 per cant of the mtal activity, which agsaa perfectly with Dr.lMxknys findinF - I have one questien. In our estpsrinsmt on mheoco ess* tnct which was published k 1977, I be6eve, we catraeted the teheeee wEth keasse end, ao. tually, dte amouat of tobecce esuaet we ob tained was about 3 per ant. At that time we found a number of polyeyclie hydteearhea, in this tabtaeaestraet. The qttesdon I would 8ke to ask yaw'Dr. Dsuekrey is: In your 70 per cent aleohol eaaatdon, how much did you eatrace theas? Haw mueh tobacro dfd you obtain on a gram besi.' it fr, of counq qaite conceivable that yme atugei is different from oun Certainly, ms the retaW bated upon human am&ea sfin.fng tktl tobaeee ehewen have an increased ruk of mouth mcer we would predict ehat tkae mmx be sotoe easelno- genie effem ako in mbaeeo exerau. In fact, even in our experimen• we got a few tuamun occuring very late. And, of eourse, I am mte• rested in finding uut in what way your eztraee may have differed from ouss. Pro(. Druckrry: To answer Dr Wyndea's quer tions, I should like to my that conudering the problem of inidating and promoting acsiqa we worked purposely with rata. As you certait. ly know, until now this problem haa been shown • conclusively to exist only in mfw skin, but we have ne indication that the saens thi,>g happent in the subeuuneous tir.ue of rats. My personal opinion is, therefore, that it would be worth6 while to look for a naf catdnogen and only aftet having found this should one search for cuncomitant facton, coeatelnosees and so oe. But everybody baa hia own way and it is aho lutely necessary that everybody foilows hia own way very strictly. We should not forges, how- ever, that the corareissogeeie effect can be shown ossly on the skin of mice and that these is no such thing in the tttbrntanecut time of nlt. - The satned potnt. Of aoune the est, tnuions with baxaoe and alcohol, rtrpeetively, an not compatabi.. The asswunt of exerattad material was about the same as the amumst of srnoke cendentate which mmn from a cigarette, i.a. ia the order of 20 millignms per dgaretts We are tryitng, of eoune, to investigate other exvutr, mo, with other tonemeneiow af aleo- ho1 and other solvents in the hope that psrhap it will heeeme posslhle to astnct seme dnsgeo- out IDatOYl. Dr. wyndn: We rtudied the same tan as yen have studied, urt A and 14 and we foessd a sGgktly ]w acdvipoE thow t.wo tast durt Ior th. •^e• an cigarettm. We thnug6t, psehapa, one raaeon might be that these tan had been ded- sndniad I wondee whedter it would be yettla Ie for yeur nts to take the total tar ineWdug the nimthta or wonEd this be mo totde2 Pre(. Dnekrqr Not it is poeble. And we wiY do Ir. Dr. Carratknr: I would k'ke te ask Psef. Dtotb my about his tebaeeo asvaetb. Was it extram. of green tobareu loaf or cured leaf? What ia the difference hetwem your eaadeeeus A and B? Pre% Drnrkrry: It wu leavta aa urd for gareete esamttatson, i~ evnsd leaf. - Whereas condouets A romea ftom nottnal ciguateet, In condosaw 8 it was tried to make the cigueao- hum more eompletsy, the mbncw luves wen cut moee fsnely, the petteity of the papee w.w inaeated and sa one ~ a0204ss TIFL 0305383
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~190 Schie.elbei0. V. Londong. W. landong, Gruiobach• Remplik, Schauer, md lounich: Nimtine and anerinxlauau I Z. klia Ctum. u. klin. 8iorhem. g. )g., s.190-196. wi 1910 Nicotine and Arteriosclerosis An Ex -mnval Coatri6ruros a the Lffraitre of n'irotiar oa Fat eVuolnfir.ar B H. Sclnevtusca, vooso, 1V. Lo.voso, FF. GavscgecH, V. Remut lutflrrt fi7r Kllnisba CSemirs nsd P.linrglx Biorbt,dir br Urarrrfttct J1ancFen (Dire.Uor: Prof. Dr. Dr. H. IVsrls) A.ScHniEs ParMloyuhr Iarrir.or der U,utrrrirar ,{idarbe.r (,Faner. Dirrlttar: Prof. Dr. I[Y. Burtgrler) snd H. 11nHCH Inutitrr2 fiv Dolw.at.uation, lefarnretioar mrd Stasittti.E enr Dratrrtua IFrbrfarsrbangr~enernm Xrr.LG'nr3 (Dirrktar: Prof. Dr. C. Wagnrr) (Eingegangm am 9• F<bwr 1970) Rabbits were gisas 1.14 mg nimt4ne pe kg bodp axight rriee dail7 for 10 monchs. The follaming male. <ee ehoie4d; 1. Total eheieuasel, nwal lipids, atecified faree geids and phaphniipida aro lnemsd toe.vds the middle of the ccpcnmene end appeoxi,nue to.the seaning eeluea at she end ef ehe s.aperimesu. Thete arc no dideeenrn burem niemmeseatedaniemis and conne/s. 2 Free faup acids in she blood of nicoebutmred aninnla an: dented aftet 8 nenrhs, IrY so after 12 months and the same as the con. tsala after 20 mnneb; rhere ehange, howtec, art nor staeiseiollg signiennt. The 9ualitetive eompn.aieioe of ehe areieed larey ecA in the blood of the nicosinessoad anisrola shoas no ditTesance as enmpued to the wnr.els• 3. $•Lipepeneains and j-lipopeotein eholastanl in she blood of the nieocinetanted anisnah w.re ssot inermsed after 20 mon<hs. 4. In nieaine<eeaeed animals, the aboee I Ipids show no inesese in hmts, lirec and leeea• eitb she esception nf feee fytr adds, which ase ele.ated in liver and aotm. In the lita, the nemnl far is aignihaneli dateased irt nicaineitmted anirrols. 5. The aaitin of tiperronin lipse is unemi•elr Inaeaxd in han and aoen of the nisorimeseee.d gmup. 6. The mnrens of nleium in the aorn of the niemine<erned gtoap is sienifitanslf incrosed. 7. HistobgioBy change aae observed, wh4ch in addition to oeher pathological endings• .hoa a sendencs to denlep anerieselen.e, bus thae ehanga eauW be abeereed in the nicaine amated and the eoneml gswtp wiah the same fsequeney and eo the aame onear. 8, When the atumels uxsn saaificed afser 20 moatha. sh: following funher rtaults t.cre obmined: In ehe hleed of ehe eau anfn.le, nn ahmuiam men ebsened in: semm crcyma, pmsebu, red and .hks blood mll mun, dseemi..e wntect, le.el of urem and blood wgas• 9. It is eoeduded from rhere saula: Snriuial•epidaaiologiai eouelaslnm bera•em the merhidiq of corumef haee dise.ee and eigasene smokieg an nor bu e.plaie.d b7 che?hasmaooingieLL ateee e4 nieeeine dane, a•hkk, rhswth.hr tde.x of oaeclwlamina, is lipol,rrk: InseaHget4em aa 4oathes umke eaastieumss am indieare.d with rtgnd m cosea.ry heaet disease. fCaokiehm eebielem eihrmd 48 3[oone 1,14 mWkg \Ikaem 2mal rlgl4eh, die loigmdm Esgehdsse svadm edsehm: 1. Lo Blus sind daa Gaemetbole.aln, GermNipide. die •caesresens Fendusm emd d'u Phesphuids neh 12 J[nnaem vehohe ued aind gegen Ends des Eapuimmoes srieder gleicls dm tuspegsrertm Ummriehiede aa•4sehm deu nikoenshehandelrm und dm Koasoll- eiam heatehm nktr. ' . 2 Die frdm Femlusm im Bloe der n7rotmhehanddsm T[ese ratm tnQs 3 J{mntea eshdlst, tach 12 Jlonarm rmiger stark uhdhr ued gleleh dmm der Kamsollm meh 20 Notutm Diaee [:ncenahied sae stuistiseb niche sigrifikasu. Die epmlinti.e Zusamrrn- taaang dar+aneaew Fetauem ko 81ur der nikennbehmddtee Tiem war nieM eenetriedm .on deeimlgm der Kmnsollm. 3. P-Lipopewiw und S-Lipoproadneholmer'ut waren sesi 20 1lonaaaa sdehe neMledm sairehm beidea Grcppea 4. Dk erayhmm Lipo4de e•aaes niehe er6blu in Here. L.ber and .korm der nikweinhehandsltm Tiau, mu .iurnahme da freim F~ aeurm, welche In LcWr and Aona aigniiikanr «hdM wum In der Labcr dct bohandeicm Tsese war der A•earsLfetryehalt emiedrigr. Si Dfe Akei.kle da lipepseteW ipesa w-ae eeh6he in Hen und.lorea dee behmdehm Tua. 6. Der Calriamgehale der inea der behandekm Tirre av ahbka. 7. HiarologiseL konaan Verinduongm beobaaluee merden. adNe. nehen and.nse patholog'nehm Befundm, die Teadms sur Ent- vicklung einer Astedne.klesere asigtm, diese Verindeeungm .ved.o jnleeh in bshvdelws ued unbehaW.km Tiesm In der glcichd H3uagkeir und dem gleieheo Auema8 bmbaehea. 8. I.ach Toswg d<r Tiese nadt 20 Monatm avrdm die fnlgendm weireea Behende erhohm: ICtine Vedrlderang wlyde Im Biae dH niknilnbehatideltm Tltre gehlndm bei; SCmellmi'JmCI, Senunpeoteiom, aocem und a•silfam Bluebild, Elekerolytgehek, I{tenuoHfpiegel and Blunnekennieqel. 9. E.:;ad .us den Eeyebniaaa gueLba.en: Sev.a:.el..pidvn.:doguei,e BaivLunqen z..ivA-, dee Sb,6Wi~ a,. w,auaan Hsa+. erl-ankungm und Zigacettmnuehm kdnnm dutth die pbaemak,ibigirchen \1'irkungm des \ikaka aLein nicht akl2rt veMea aelden auf dem 14'sge da Fselsaaung mn Creehinaminm lipelreisch wirkr.ll"eieese [:mmuehungen isn Hbsbliek au4 din Beefliw guag andeta Bauehbeumdtdla in beaug 1uf die comnasm Heeatrkeankangen sind mgae4ge. PA - 000468 TIB'L 0305385 T0020g87 z.klin.a.m.a.klin.Blaeee:.re.tahM lr.orHdr3 '•'
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1-188 (2) tJOTlCE: T`iIS M,ATERIAL A4AY SE f's?i; iT-.CT 3Y COPYRiQHT LAW (TRL£ 17 1:.S. L:iJ+ir_) tables and death rates in U.S. vital statistics for 1962 (approximately in the middle of the five-year follow-up). The least favorable aU-causes death rates, expressed as ratios of observed deaths to deaths expected to match U.S. experience, were east Finland (0/E=1.34); Slavonia, Yugoslavia (OlE=122); west Finland (O/E=0.96);Crevalcore, Ita1y(0/E=1.00); Zutphen, Netherlands (O1E=0.95); and U.S. railroad men (O/E=0.82). The tanfavunble mortality in Slavonfa was accounted for by death causes scarcely seen in the other co- horts-tuberculosis, suicide, cirrhosis of the liver, and acute alcoholism. The U.S. railroad men, being fuUy employed at entry were expected to have a lower death rate than U.S. white men in general. The other ten cohorts were expected to provide 3A4.7 deaths; the observed number was only 188 deaths, 0/E=0.545. Great differences in CHD death rate accounted for most but not all of the differences in all-causes deaths, In the same ten cohorts for which all-causes death rate KEYS gave 0/E=0.545, the ratio of observed to expected CHD deaths was 24/139.2, or O/ E=0.172 in these ten cohorts there were 157 fewer all-causes deaths than expected; the relative rarity of CHD in those cohorts accounted for 115 of the 157 expected total deaths that did not occur. In contrast, in the other six cohorts combined, all-causes deaths were 98.4% of those expected to match the general population of U.S. white men. Among U.S. railroad men age-standardized death rates from all ratues were higher among switchmen (physically active) than men in sedentary occupations while the reverse was trne of CHD deaths, but in neither case was the difference statistically significant. The same was true when comparison was made of men free of CHD at entry. Ineidence of Coronary Heart Disease Among 12,529 men judged to be free from CHD at the entry examination, the five-year CHD experience, in a hierarchy of mutually exclusive diagnostic categorles, was as fol- lows: 116 deaths from CHD, 113 nonfatal Figure S2 Aqealand..dised manee yearly CHD ine6len<e rates per 10.000 nr I-0:da meu es d 0,19. iudai 1 to be free of CHD at the outs.t, follonal fue et'e yeare. Son-f:asl CHD luedence in Jnpan u not precisely Indicated becease the rnkvant i-year rlinicnl unJ F.CG reconla atre nnt inAependently m rierved rt the University of \finnetola ceater. MEN 40-59, CHD-FREE AT ENTRY CHD 1tdCIDEtJCE110,000lYEAR 15-20 JAPAN 32 GREECE 53 YUGOSLAVIA 100 ITALY 7 33 23 56 139 NETHERUNDS 177 U.5 RY N8 FINLAND S.Ods.ws I a Rs.41 . Vd.. X11 wd XOI. .ladi 1910 TIFL 0305432
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(3} NOT,CE: THI$ MATERIAL INp,Y BE PROTECTED BY COPYRIGHT LAW (TITLE 17 U.S. CODE) La k of Correlation Betw en Antemortem nd Postmortem Diagnoses` JOHN PRUTTING, M.D. New York City A ending Physician, DCCtnrs Hospital and Belbvue oepitsl Center, Second Comell Divisioe . L. Merrc N defined a judge as "a law student who dea his own papers." A similar view ml ht be taken of the physician who fails to su m]t his diagnoattc skills to that impartial grader, the autopsy. It is disappointing o have one's diagnosis of coronary occ] 'oa become, at autopsy, a pulmonaey e , ruptured sortic aneu- rysm, dissectin aneuryam, or an abdominal disease such nj paneeatitia, but nothing is more instructi , The case for the autopsy rests solidly on the we3l-do ted fact that antemortem disgnosis is uently refuted, clari8ed, modified, or ~ borated by postmortem ez- amiaationu e caee against the autopsy reate on a gruuada, priacipally lay re- sietance and e lao]t of time by profee- u oaal pereona to perform the autopsy. -Ia tha com etition for the time of the 9eJOian, the autopsy bas two atrikes Bsiaet It: t e emotional reactiona of People, inclu ~ TL6, ai pp ~p ey aa~m ~ b A 0*ON eNT6N0aTari D1AGN0®a fs fr&juent(y n- /a1ed, rlariJied, modified, or elaborated by poeanarcem eran<nation. Nothing ia more inRructiuz than autopsy. Autopsy is needed =o oorrxt false diagnoses and to enlance medi- cal .Fnoaiedge and diagnostie sbiR. difficulties in obtaining consent because of archaic state laws. But means must be found to educate the reluctant and to bring about a change in such ]aws. If un8niahed autopsies pile up in the pathologist's office, the solution is not attacking the autopsy but supplying the pathologist with the equipment of modern technology. I Literature The literature abounds with ezamples of i antemortem versus postmortem discrepan- ciee. Some of the more striking ezsmples include: PvcatoNAx: snsolasm. Of pulmonary embolism cases studied at autopsy, an aver- age of less than 50 per cent had been diag- nosed correctly ante mortem. This figure ranges from 10 to 89 per cent in various aeries.' Hodgson and Good+ believe pul- monary embolism to be responsible for 47,000 deaths annually in the United States. The awareeess of the incidence of pulmonary embolism, as detected by au- i topsy, has enhanced treatment and preven-- tion. Eztensive use of the autopsy can only incease medical knowledge about this dreaded pathologic proceee. - GAaTAOneTSB'raUC gMggo3aseGm. In 200 terminal caaes of gaatrointeatinal hem- orrhage, autopsy showed the clinical diag- nosis to be inoorrect 38 per cent of the time. The most common causes of hemorrhage ., were peptic ulcer (85 patients) and esoph- ageal varices (70 patients). Bleeding peptic ulcer was misdiagnosed in 37 cases.. Esophageal varicea were incorrectly diag- nosed as peptic ulcers in 11 cases, and gas- August 1, 1967 ( Nrw York State Journal of Medicine 2081
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742 C(GARETTE SDIOKING AND DOGS-XA.HBIOND F.T AL . warda by com uter-genera7ed random numbers, Eight (group .), seleaed by random numbenm never smoked igarettn, but their tmcheosto- maa were kep open fnr the duration of the erperimeat B chance, one or mom of them was in each of e five warda. During xve consecutive days the other 89 dogs (ie, all e t the eight group N dogs) were gtven un ihted cigarettes to familiarfae them with the situation. The smoking of light- ed <igareltn gen May 2 1967. "day I" The first 55 dayt en us+d to train the dogs to smoke and ha itwte them to tobacco axoke. OnlySlter-tip garettee were used during this aeriod. On day, 1 through 14 each dog smoked one filter-tip ci arette in the moming: on dayY 15 through 21 ach smoked one in the moming and one fn th afternoon: on days 22 through 35 each smoke one in the morning and two in the afternonn; on days 36 through 56 each smoked two ithe morning and two in the afternoon. Th each dog (ezeept throe de- scribed below) smoked 154 filter-tip cigarettes during the firs 56 days- From then until the end of the ea eriment. each dog smoked ciga- rettes in the orning and in the afternoon of each day, seve daye a week. Tbe tbree d zs mentioned above .vere elimi- nated from th eaprrimaat before day 57. One swa withdra., from the study shortl-v after day 1 when a ophthalmologist examined all the dogs (inct din,e group N) and discovered that this anim had a brain ttmtor. One dog died an the 3+ d day of smoking atter having smoked 61 61 r-tip dgarettes. Autopsy re- vealed the ca of death to be pulmonary infamt7nn wit multiple embolf in the lunga. Another dog d ed of bnnchopneumonia nn the 52nd day aft having smoked 134 fl(tar-tfp cigarettas, les 'ng 86 smpking doga in the study. On day 5:, these 88 emoking dots wen divided into to r groups; F for filter tip. L forr light smoken of nontllter cigarettea. H for heavy smoken f nanfilter cFganttn, and h for another group of heavy smoken of noaftlter cigarettes that weighed mon. There w.n 12 dogs in gmup , 12 in group L. 24 in group H. attd3gingrou h The 48 ligh dogs in groups F. L, and H wen divided stnti8.d random aelaetion to irnun that e fnm eatIs grnup would be In each of the p air+.onditioned wards in a new. specially eted laboratory. Each ward had 20 pges tstl an alcave at one end with equipment for ing dogs to cigarette smoka A hood with exhaust fan was placed over the eqtdpment so that smoke would not eetvpe into the ward. fnitially. thelpump waa wed to deliv.r smoke front cigarettn into the trachea as previowly deacribed After a few weeks, the dogs became habituated to cigarette smoking and seemed to enjoy it as indicated by tail srag: ng and /ump- in; into the "smoking bos" vafuntarfly. There• after, the usa of the pump waa discontinued and the dots voluntarily inhaled unoke by dmwing on the dgnrettea. • Days 57 through 140 constituted a transition period in that group F doga u'ere kept on filter-tip digarelt.a whila grcup L, H. and h dogs were changed gradually frvm filter-tip to nonfilter cigarettea. On dnyz 141 through 210. group F dogs smoked six filter-tip cienre<tes daily; group L dogs, three nonfilter cigarettes; and group H and h dogs, six nonfilter ciga- rettea. The daily number of ciganttes was increaed gradually thereafter to nine ciga- rettes per day for group F. H, and h dogs, all of which smoked nine cigarettes per day for 29 wealo before aoy wen killed. The plan was to expose group L dogs to half as much tar as the group H and h dogs during the experiment To campeneate for the fact that all doga smoked the same number of ciga- rettea during the &nt 56 daya, group L dog. were given fewer than halt aa many cigarettee as group H and h dogs during the remainder of the experiment Survteing group L dogs smoked fiw cigarettss per day for 49 daya hut lesa than this number on all other days. During the last year befon being kliled these dogs amoked only four cigarettea a day. During the experiment three dogs betame acutely ill with fewr and other symptoms. One belonged to group H and two to group h. These dogs were taken otT smoking for a few deya ard tnated with antibiotics. IVhen they recovered. they were put back on senoking. The group H dog (H692b) survived until the end of the experiment when he waa killed The degree of librosia and emphysema was about the same as in the other group H dogs at the ttme they were killed. Both of the twro gsoup h dogs survived until after the time dogs of groups H, F, L, and N were killed. Table 1 provides some informatfon on each of the four groups of smotdng and nonsmoking dogs. For aomparuon, data aea given on the total expwun over 875 days of dogs surviving for that long ar longer. Ftgares for total tar and total nicotine conaumad are based on the as aumption that the dogs naxioed the same Quantity from each cigarette as when cfgarettes were smoked by a smoking mnchitte. The dogs actually received a Little less tar and nitotine than indicated by then figurea sinee aame por- ticalate matter corklensed in the ntbing leading from the cigarette to the tnehemtomt The Tat No. cf aaaa on eay . Dceme un eays 5 Z deed Ag/ at stsrt (day 1) uean ate (yr) vovnaesteo,t(rr) OWest eat (yr) wergnt el enrt(ay M.en vpgnt .g (1'. Ganteatdoe srfIc He.d.rt CV4 ka (fr Cfg.rettea per ae"n Mean Me. ef dgarr Eeuiralent No. Ef e day rsr 6a.0.k; (: ryce ct desrenes; Te, ryneMt Mr ngr Nieetineeomeneor Tobl dowa. in ars c. Gram. at ar oer do: Gnms of nifotlne ae oasaga n 6)5 Gya n startingrMgnn Gnma ol tar ov p Grameof n1coMIM: .eight - Tne fmok/ng doqa t These nguns eaali :Oegs er gmua L. M aut amoMee nonPoUr C difTerence between filter cigarettes was puting total toc anc 875 days. The size a In estimadng adecti. of animals at the ar taken aa a tomtnier reason. Table 1 show consumed over 875 starting weight of c this index, group h ir to tar and nicotine t, half that of gmup tirres m much extwr ArcA Enoiron Haalth-Vo1 21. Dee 1979
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t:zt '.L-er.. c=-_ -e any _*co:-daag~in~ in ._^s oi r•h.:.°: aci:ons ar3ag9vo~:_::ce Sor PA - 000479 Q=na_.__nts. - Qu_s'tion. Ar- T^rry, ir. t2_a li~it o: :~2 dc2____c_css o° the '':..^.d'sags oi Lis rxport, in tua iiglit of yo:zr , _s C ~e_Abes ec `CG! _.J::sv oi_*:eieC_tes oT L._,. lLBric:7 to !i]OS• ?olL ' co'~.~.1°^_t on 'C1e ae?`1on or Go_^a arOD~r'~ IS° •.^.aCt_o7 ..~ ._,. .u~. Ec~se o4 DeLeg~tas at itz most rscent neetiu~- on 2h=s sa°.j_ct oi .._a1t:i _......_ds of c_... „ . Dr. Ta^y: I;Os?da't 1i1.'e to co:u2rt ot tL^a actlioa or inactioa. c..u:cly, in aaay res?zcts I tcia,:L~'.e I[c-~ o= Delegat3s si6Gt Fs:ve Leen disC cot to tal<a any '•ctLO+3 avaitlr-s '~:Qis .-aport since I b=iieve nost o£ us Pelt it ce= a nost co=nrahaas've raport aLd un8ost_s.t^_iy c!a could not eake it a:a?lable a.t c2:e ti::e o-- C_e 3ouse of Deleeatescoeting in early Deceaxr. F Caonld not be crit¢c:1 of r!hat has been done. I'•+ou?d bs very aa.:icns to see ~T`t nill be done by the P.3L1. . Question: D.^. Te-ey. 1.Gon't hnoa i£ t`e Coamittc involved in any s13•„Fr?Lne of ¢•.:abars,• , brt i£ tuere is if sce one oa the Co^?ttee cou2d. aay vay oY Sayi=,- this./h tu~ vere aa s:.oain•; ia t._ tiait^_d s..-tes toGay, vhat anprecicble dif2ereaca =-z'd it p_an to ;iggures far tlis A.Tar,c.:n po,ulnt:aa: Dr. D=. iButl _y, I:i::e to -Ci° Y, 'T0020530 7~ TIFL 0305443
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-Z- Nov of course the death toll due to cigarette ssoking is by no meaos the only harm that cigarettes do. The amount of illness and suffering short of dwth caused by cigarette smoking, is truly of staggering proportions. It may b said that the emerging medical view is not that eigaretta asoking seriousl damages the healtb of s' people who practice it, but that cigarett smoking damages the health of most people who continue to smoke. All this is why the 17 organizations which meka up the National Interagency Couneil ve before th® such a great opportunity to help awe lives and to help imp ove health. It s most eneooraging, as Dr. Terry pointed out this motving, thst there ha already been soma reduation in cigarette smoking and we may " act more res lts from the many veil organised education programs now being carried in this country by thousands of dedicated people -- sueh as the progrems referrad to by Dr. Marrill. But we believe that wost 3ecisive progress _ossrd reducing cigarett cooneption cannot be made while cigarette advertising ia allowed . to flour ah unchecked. Cig ette advertising is now running at the rate of over two hundred million ollars a y.er. The contiaued exiatence of this volu.e of advertis- ing offs ts, or one might aay engulL, counter-edncationel efforts. Nobody in the I tarageney Council believes that the aala of cigarettes should be prohibit , but we do have grave doubts about permitting the promotion of cigerett sales -- to people of any age.. We elieva it is not morally justifiable to encourage people to kill therelv.ie. T 005:0534 TIB'L 0305447
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. Editminl TRE UA\V77[ORNE EFFECf Roben!- Loineond Era D- CeAm ABLE DATA: PUBLISH OR RE]ECi'? Lou OedrPsy py+ 111 pqelll • Artidn - - QU4LtTY OF CARE ASSESSMENT: THE1FtOLE OF FACULTY AT ACADEMIC MEDICALCENTERS `RobetH.Brook pqe11S AN EXPERIMENT IN BLL+iD PROGRAM SELECTION . Harold O. C~ pe,p 129 Poiitian Papq , POSITION STATEMENT OF THE AMERICAN FEDERATION FOR CLIIYICAL RESEARCN V THE PROPOSEDPOLICIES AND PROCEDURES FOR PROTECTION OP HUMAN SL'BIECTI pep Il1 , SLBS/1i7E0 TO TRE A-MERICAN 5OC367Y FOR CLDOCAL NVP1VIIpY --qrye 5794 ACCEPTED BY THE NORTIlwE,SP SOCIETY FOR CIINICAL EESEARCB - Pera S87A wESfERNSECRON . . Cutayo,Bloo: . <RNSECItON . ; Slasbmatb 5 tiTNERN SECTIOP( ~ O:lnro.loui:aro tw scenv:ecclvsf . ATLANTICCITY,.`AAY4and5.1974 PROGRAM AN NUAL MEETINC OF THE A1IERICAY SOCIETY FO R CUNLCAL INVESTICATION, hteetin,,e1, ~ ~ NATIO:IAL MEETL`3G OF THE AMERICAN FEDERATION FOR CLINICAL RESEARCN. d. Ci tomi w.(. 147 - , ATLANTIC CLTY, SIAY 6,1974 PROGRAM p.ge 177 ANNUAL M,EETLYG OF THF ASSOCLITION OF AMERiCAN PNYSICIANS, . ATLANTICCITY.5IAYT,1974 PROGRAM pase 177 SPRINO SIEETING OP THE SOCIETY FOR 1N VESTtGAT1V6 DERMATOLOGY. • _ ATLANTIC CITY,MAY 4, 1974 PROGRAM pqh 179 , ANNUAL MEETING OF THE AMERICAN SOCIETY FOR CLDiICALNUfR1TION:. - ' ATLANTIC CITY, MAY 4,1974 - PROGRAM yoy. 181 . ANNUALNEETDiC OP THE A-MERICA,N COLLEGE OF CLE'UCALPHARMCOLOGY, -. ' ATLANTICCZTY,DtAY7aud4,1974 PROGRAM pqe/8i BtEElIlVG ~ - ANt1UALMEETUtG OF THE NORTHWEST SOCIETY FOR CIDIICGL RESEARCtL -" Cosapundenee pap 139 ' NotfC4. pese 1lI ' VANCOUVER,BRITSNCOLUMHIAMARL$1.1974- PROGRAM pesel86 Ab97BCD . 'SUB)IITPEDTOTFM ASftRICANFEDERATIONFORCLLYICALRESEARCR paselJyA* - -" ACCEPTEDBY TRE SOQETY FOR UNVEStIGATNE DERS(ATOLOGY,ItIC port j7J.! - Oaobw 2, t974 IanafPtOdt,l973' ' la.uaq ~DA.brsar 1, 197! Oeroen11,1974 -~- Pe6eeeqb~B,1973 ! OOZ0Jr24 •
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i NATIOnN. ~lRPSNCENCY CCONCIL ON Sh10RIIiG AND HEALTH 8600 IJUeLn Avenue Hethesda, Maryland 20014 FOR RE<l.IA4E AFTER 12 NCCN, EST, MONpAY, JANUARY 11, 1965 Stateesnt of Pmarson Feota, Chairman National Interagency Council on Smoking and Health . The ational Interagency Council on Smoking and Health is meating here •in Washin ton for two days to add impetus and planning to a movement already well ,mde y in many parta of the United States. This msant happens to be th• greatest life-saving and health im- ptw®ent enture of our time. I refer to the national moveaent, made up of many 1 a1 movamints, to reduce theconsumption of cigarettes. For c garettas kill people. And they kill people in very large numbars. Ths ited States Public Health Service knova this, The American Cancer Sec ety knows this. The American Heart Assoeiation knovs this. The American P lic Health Associstion knows this. The National Tuberculosis Assoc£ati knows this. The Royal College of Physicians knows this. Physicians all over t a world know this. Just ov many p•epl• do c`_g•retees ki1D Even the most expensive computsr couldn't t 11 you exactly. Est tss oad• by scientists, who have spent years studying the problm, vary d ing upae the wy that the data •re interpreted. but 1 mq be said with nteaess that cigarette smoking is today responsible for at least 123, deaths each year in the United States. Cigarette s.oking 2!1 be re onsibl• for as many as 300,000 daaths_per year in this country. figure repraseats a national catastrophe. EitbE There are, of course; many hazards in life but in peacetime ther•.La noth£ng e1 • lik• this hazard -- not automobilas or anything alss anyone ' w esn think Af. r 00;:0533 TIFL 0305446
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1-109 ,_ ......... . .. .„ .uct.lJiECrEt3 Bv COPYRIpHT LAW (TITLE 17 u.s. CODE) at anushimaru. roughly double among the you ger fishermen compared with the farmers of orresponding age; for systolic blood pr ure of 180 or more at rest, the probability of hance explanation of the differences is p c.02. At ages 50-59 there was oo sign cant difference in high blood pressure pre alence between the Japanese fannen and the shermen. A all ages these Japanese men were clearly less prone to high diastolic blood pressure th the U.S. railrced men of the same age. The differences shown in figure X.1 in the pre lence of diastolic blood pressure of 100 or ore mm Hg are highly sigoiJ3tant with p<.01 for both age groups when the com iued Japanese men are compared with the '.S. men of corresponding age. Diastolic bl pressure was measured in the fifth pha (disappearance of sound) in the Jap e men as in all other men in these stu 'es: Conceivably, the fatter arms of the Am ricans may lead to earlier d'uappearance of a dible sounds. It is notable that as shown in gure X.1, the prevalence of systolic h rtension among the Americans was not sig cantly different from that among the Jap nese. e distributions of serum cholesterol eon- cen tlon at ages 40-49 and 50-58 are sum arized in figure X.2. As in figure Xl, the dat concern the men found to be CHD-free at he entry examination. In none of the coh rts covered in figure X.2 was there any sign cant age trend from the forties to the fifti ; presentation of the separate data for the two age groups simply emphasizes the co istently marked differences between the t cohorts. The most eztreme difference is tha between the Americans and the Japanese in g rai, but there is also a highly significant diaerence between the men of Tanushimaru,~J wnh the center of their distribution close to = 170 mg/df and the men of Ushibuka with a corresponding figure only slightly over 140. Attention to the cholesterol disaibution in more detail is illuminating. For Ushibuka 95% of the cumulative distribution is reached at less', than 200 mg/dl while around 300 mg/dl is the] corresponding value for Tanushimaru, nut_ very much lower than the 951 coverage poin[ of a little under 30 for the U.S. ruilroad men. ;; Blood pressure distributions are shown in' figure X.3. The usual trend of the systolic' blood pressure to rise with age is coosiderably more pronounced for the Japanese than for the Americans. At the younger ages very high blood pressures were more common among the Americans than among the Japanese; at the older ages the situation was reversed. The meaning of these differences deserves more study. In smoking habits there was very little difference between the two Japanese cohorts. Both at Tanushimaru and at Usbibuka more than 70% of the men were regular cigarette smokers; 408 of these men smoked at least 20 cigarettes every day. At entry the Japanese were, in fact, the heaviest smokers of any of the cohorts in this [nternational Study. Japa- nese men have tended to be heavy smokers for many decades, a fact noted in our surveys in 19G6. Unlike the men in most of the European cohorts of rural men in the present study, the Japanese smoke cigarettes made of America4 "V'uginia" type tobacco. In the U.S. and European cohorts in this study, the proportion of men who have quit smoking increases with age, but this was not true of either cobort in Japan. Tables X.1 and X.2 concern physical actlv- ity. Very few of these middle-aged farmers TABLE X. I RURAL JAPAN. Pereentages of men of specified age in physical activity classes: 1= sedentary, 2= moderate activity, 3= high accivity. Entry data. ACTIVITY rANGSHIbtARU USHIBUKA 40=h4 45-49 $0-54 55-39 10-+1 45-49 50-54 i5-59 1 3. 4 3. 4 5, 1 L. 7 2. 6 7.6 7.2 11. 7 L . 36. 6 41.9 ,... 4019 ,#6,.2 le. t. 16. L_, 10.3 24.4 3 58.0 54.7 54. 0 ?t. 1 79. 3. 76. 2 82. 0 63. 9 SMCf.+r>Y f te CircWis.. Va6. Xfl .et Xtlt, ACra 1910 TIFL 0305430
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-3- Never beleas the members of the Council would not favor a lav pro- hibitiag c garette advertising. We do feel, hovever, that legislation may vell be ne dad to counteract the effect of cigarette advertising -- by requiring varning message in all advertisements and promotional mAterials. However, t sre may be another wy - even though it may sound rather out- landish o first hearing. That would be for the tobacco companies to voluntaril suspend!lcigsratta advertising, This would be more in the American t dition than =n sort of lav requiring tha restriction or altering of cigaret e advertising. I bel eve that the tobacco companias would do this nov, except for one thing. I an only guess this; but I don't think the people who run the tebseco c anies evan yet believe the evidence about cigarettes. I think thatif the felt as va do in the Council they wouldn't wish to advertise cigarettas I hav great reapect for the tobacco cosqanies of this country and for the c tribution they have made to the etonoodc welfare of our nation for 300 years. I believe that these aospania are run by responsible mm, who vant to do the ight thing. Yros ublie stateswtts they have made, it is evident that soms of the people in arge of the na:_on's tobacco companies feel that tobacco bas alwys be under attack b7•one group of zealots or another and that, to use a phrs ei "this too, shall pass swy." But the point is that when King James I uas writing his "Counter-Blaeta Againat Tobacco," there ueren't any scient fic facts on either side. It has only been within the past 30 yatr: eha! s<ieae. fve reelly geni eo vnek en Cha to6:cee-haath vroblat 70020535 TIFL 0305448
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-4- end the idence eonfirming the lethal affecta of cigarette smoking now amounta o a tidal vave -- coming frw all couatsies of the world, on both sidu of the iron curtain. ld sisply lika to suggest, most respectfully, that the gentle- men in.charge of our tobacco companies re-think and reconsider the uhale matter - re-examine the evidence open-mindedly. I think it is poasible that such r ideration migbt'lead to a decision not to advertise cigarettes. I d not mean to be preaumpttloua but suth a decisiop would also appear to have his advantage to the eoeqranies: it would definitely isoprove their short-te profit position -- during which time conversion to other activiti s could be undertaken. Als , vhile we fully recognize that cigarettes today make up the largest ad most profitable part of the tobacco business, they are not all of it. d both pipe smoking and cigar emoking fall into an entirely differ category than do cigarettes. Re t scientific studies indicate that inhaling is probably responsible for moa of the health damage caused by cigarette ®oking. Hot many people inhale ipe or cigar emake. Th e is no question that serious illness is caused in soss instances by both ciger and pipe amakin4 but every mortality and morbidicy study aIr shoae this to ba very much lover level than the effect produoed by cigaratle emcking. ng personally, 1 am not.against tobacco. Z am against cancer, heart Wsease,and eiqfbysema which are so closely linksd to the use of tobacco, spacifi4ally in the fors of cigarette smoking. Even ao, I a not against the sal of cigarettes; but only against the proaotion of cigasettes. T 0020536 TIFL 0305449
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CIGARETT Cwnx The committee ^u}burn Houae I~residing. LABELING AND 3DVERTISI\G-1969 ffiO=&Y, APIIII. 28, loee Horse or Rrsarssa°rsTt.•es, rra o} I.rraararx aaD Foaxmv Coxxeace, li'axhfngton, D.C. met at 10 n.m., pui9mmt to notice. in room 3133, 6ce Building, Hon. Harley O. Staggers (chnirmnn) 0 The Csata>L.N4 The committee n-ill cotne to order. We are in conrnuntion of the public hearinFs on all bills pending hefore the comtm tee relntins to ct~nrette labeling and ndcertising. Our first Ritne this morning n~il1 he Dr. Victor Bultler, pathologist, ]umsas City, 31 Dr. Bubler, ue ~tre hnppy~ to hare cou nith us. Do you hare al long stutementi' STA H„er; 0F DB. YIGTOE BIIHLEB, PAT80LOQI3l, SdR9aS CITY, Y0. Dt•. Botasa.l'rybrief.3fr. Chairman. You mny proceed An pou see fit. "Ll:e Cxaatua. Dr. -v name is \"ictor Buhler. I nm appearing before . BC•HISa. ~ the committee o the request of An attorney in Kansas City, who represents the to acco industry. At the present time, I am the path- ~Jngist at St. Jos ph's Hosprtal, Kansas City. 6So. I formerly serred x, pathoio~st at General Hospital. Knnsru-City, Mo., and St_ ~Iar- tu•et's Hospttal nd Providence Hospital, Fansas City, Sans. I I estimate that .\t oue time, whi n , T00. In additi ertions and muc I was gtaduat deitr•ee and in 1 q deportment performs about 300 autopstee a tear. at General Hoepttal, the figore was probablf closer . of coane, I see ihousands of biopsies aad frozen other patlwlogicalmaterial each year. . d from Iiansae University in 1930 with an A.B. with an M.D. degree. Following 1 year of a rotating enr as a resident in medicine at dttcker Hosuitnl in 0 internship and 1 S•. Pau] Minn., serred } years as a resident in pnthology at Cmneral SG„hit:~ in%an City. I nm cer6i8ed y the•?.merican Board of Pxtlwlogy in both pnth-. nln_ ic anntomv a clinical pathology. I hold a tenchi eppoiatment as acesxiate clinical orofe-nr of path- In~md oncul at the Lni.vetsity of Kansas School nf ~Iedreme: ~'nneology"m thestudyoftnmors,inclndinlCCnncer. I seraed ftom Odober 1963 to- October 1985 as president of the N'Ile2e of Amer an PatholneiaM. This is a national or2nniaation nt pathologists, ith a membership of appro:imntely 1,300. I have `M' T0020526 TIFL 0305436
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10. Malignant Nenplanm of Lung, BronchuR and Trachea (3) NOTICE: THIS MATERIAL MAY BE PROTECTED RY COPYRIGHT LAW (TITLE 17 U.S. CODE) The fiznea in Or.nk ader. 1950 -51 Male 1952 1954 1056 1950 -53 -55 -59 1960 61 106 64-65 1950 -S1 1952 -53 1954 -55 1956 -57 1958 -59 960 -61 1962 1964-65 Sex Rslin 1964-65 19.54 22.24 26.13 20.33 29.37 32.46 32.29 36.71(11) 5.67 5.47 4.72 6.63 5.83 6.23 6.14 6.52(6) 563 Gnd~ 14.26 16 97 19-36 21.59 23.35 25.42 28.77 30, R3(16) 3.05 3.42 3.76 3.4a 3.49 3.64 4.32 4.73(13) 652 Chilc 9.88 11-22 12.62 12.58 I3-64 13.57 13.83(23) 5.35 4.74 4.40 4.48 5.01 4111 4-69(14) 291 Un~d.l Si:nn, W6i1c 18.44 21.39 24.03 27.17 29.37 3L36 3.90 36.86f10) 3.83 3.95 3.97 4.20 4.41 4.69 5-2Z 5.83(9) 6 32 U-o-d Sialcq Nanabdc 14.51 17. 8:1 20.33 25.17 28.23 31.08 4.66 37.72(9) 3.44 3.72 4.07 4.28 4.94 4.77 5.55 6.09(8) 619 Israd 12.94 12.95 16.42 17.70 17.06 19.10 17.35 20.83120) 5.76 5.94 5.13 7.82 7.72 6.59 6.03 6.75(4) 309 lol.m 2.65 3.61 5.25 7.07 8.64 9.97 11.45 12, 64(24) 1.02 1.37 1.94 2.58 3.25 3.67 4.09 4.4fi(15) 283 Gcmm.y. I°nl. Hrpnb. 22.39 25.16 29.52 31.64 34.73 38.37 40.30( 7 ) 3.81 4.03 4.14 4.23 4.50 4.80 5.15(11) 784 Ausha 38.78 40.01 45.15 45.92 48.85 48.89 49,39(5) 5.30 5.18 6.14 6.30 5. 5-99 5.70(10) 866 )SclBimn 25.92 29.74 31.90 27.89 42.14 46.72(6) 3.56 3.45 3.65 94 4.23 4.41(16) 1.059 Ihnnvrk 17.77 19.58 23.30 25.59 29.75 32.14 35.84(12) 4.21 4.26 4.40 4.50 5.50 93 6.57(5) 546 Firderd 4.'5.26 44.82 47.4/ S.S.OR 55.98 59.19 60.12(3) 4.22 4.26 3.84 4.07 3.25 85 3.77(20) 1.611 Fr, re 10.70 73 24 15.62 18.13 19-01 22.22 2.9.77 25.55(19) 3.11 3.18 3.28 3.39 3.37 3.38 3-58 3.57(21) 716 Ireland 11.02 10.07 21.25 22.26 26.09 26.89 28.00(17) 3.57 5-55 5.82 5.28 5.75 6.90 7.0](3) 412 Iraly 11 13.79 17.00 18.55 21.46 23.81 2t 57(18) 84 3.08 3.44 3.42 3.92 4-03 4.34(17) 635 Nnr..ay 7.20 8.22 8.86 10.64 12 32 12.62 13.89(22) 2.6.5 2.45 2.41 2.48 2.51 2.58 2.57(24) 540 Ncdrerlanriz 23.78 6.41 29.97 33.84 31.30 42.32 47.47 51.12(4) 3.29 2.92 3.01 3.13 3.00 3.40 3.34 3. 39(22) 1.500 Ibe6g:J 7.23 7.86 8.72 9-70 10.09(25) 2.46 2.05 2.37 2-44 2.19(25) 461 ling)nnd x,d Welks 39.08 44.49 50.49 54-75 58.90 62.22 65.05 67.72(2) 5.85 6.24 6.50 6.91 7.34 8.10 9.80 9.70( 2 ) 698 Scndand 38.59 46.32 50.30 56.30 61.91 66.06 71.57 75.55(1 ) 7.'72 7.24 7.51 7.69 8.95 8.71 9.38 11.44( 1) 660 N~rthcrn lrelxnd 20.47 22.78 28.46 33.76 34,05 36.24 38.51 39.49(0) 3.32 4.60 4.87 6.17 6.18 5-19 6-14 6.30(7 ) 627 S..aJcn 9.On 10.34 11-I1 13.0n 16.49 15.19 16.44(21) 3.74 3.45 3.80 4.03 3.71 3.85 3.78(19) 435 S.~iiurlmd 23.68 26.20 27.20 28.03 30.32 31.70 33.39(15) 2.96 3.00 3.19 3.05 2.70 3.28(23) 1,018 Amtral:. 13.89 17.29 19.42 22.48 24.57 27-6 31.52 34.58(14) 2.80 3.33 2.94 3.26 3.21 3-41 3.80 4.19( 18) 825 Ncw 7,lnml 17.42 2120 23.81 27.44 28.37 28.5 34.33 35 ,712(13) 2.89 3.17 2.67 3.N 3.70 4.41 4.80 4.92(12) 726
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281 w ettll do t knw hw to oANro that owry child with a Nso threet has a threae culture or hw to trtN dl sweqttble ehlldrtA la omup to prtwat bNtt dtsrN. ln the pNt rN d.eedN. w bew leetAJ hw to uN nw dtup a lowr blood reeNro in hypKtoaatw Ntttaee to leNU the eisk of strokes d heert tollurb ltut w still do Nt kaer uhat csuNs Nst otu of hith blood ptuwN, hw to weteots the popolttion t be trrtdetd fot h!M blood prtseure, et bw to initiate and inuin otteatiw thotApy is all thooe with kyh hlow ptost Me bew lot how to oubtttrtAe the burts ot t.sll bdttot to tdtnttfy o onltal heart loslou. W hw to dateNt thw by epN heart o racteta. eut w do net tror hwr ANy Noysaltal eoNita dot a uo ynotts or hw ry rdlNt the ewitarot of the ltcus tld, e70tapt fN adtl ddfKtA hnew to ht dea to rubolla viru, w do wt tmv hw to pNwee owjesltH hurt d1oNN. . vo knou hw, y Nr{laai pnwNures, to entoae or byaoas atheNatlaN ie otatruttione in the IrtNNt. tut Ye d. Itle knw hw to pre t ethtreoelorwia w hw to dl.pNO d treot it Nrly. . ve haw eoth tteatN physteleoul NsN that tell us prtataoly . the tunstiN dofssta of dlssttoo et luass. 7ut w do not knw the eoNs et alsonary wthrswt, hw to atq !ts ptottoN ovon if dottttad set , or hw to prowN fswt dts.se stusod by t.physoto• . tio tasr the lfit olottiy (wtw MotA dstlstaety atww hd.etrho{s yaltntd v1tA Nrt`ttle. fa to troN thoN petioato rsplrN hs Nlh{ No lwcAts (tt+A vtyo thaa 70 pyewt of the nulsul hl supply. W do Att tatr kw to oktelA thtN f.eew. Yltk tNN LA eett•AftteelwYM{ AAlt1Nr haeA w dlNewred altotnAtiw ottrneo. ao tsM to ohat t aor itNrento by dthlW it Nr that a pNh1sA bN Mon Nled uhN it h.o, taet@ booe oAly belt MIvM. We etss taee uy to our /twNnse is eonr ito tors d Naop{!as thN a wttttly ditatrwt type of hewledp tho w nn htw nlll be ANaoNyy to fully Nlw t/{ow prNler. t by u e surNt wy so Nw the prblta'o beoltfrdAllor to tho lws tYA !s o e tin a e N•oa1M untswtdedtAq ef tho onalunltr eausl.t hNre• b1oM weNl, lua{ a blood dtsoN.o to pt"t Rovwttw or taqloes auN. rhe iNO w know eMet a tasNd, the 1Ns spsettlc !s the trsatAwt aM the Scastor the test. tpe/t/e ravantlw NA de!lAttiw trNt.Nt uanolly eeot rttattvely littlo eN ayt t.al trsr/atw Mte KNNtw Netw. • iv.nty-Htt Ns ys, all w eouU offer Ntlsets rllh eoNreulosis wo ANyee te .e.aertr os survied sara uhieh uN rery Nsely aod not wry etteetlw. Ye w hne spNttie sh.wehorayt ts !e both a!lett& and ehN". • rtWtq fsst rt thot trtdws rhowtie te.w ad a uq to pNwet ehourt/t h rt dlwaN haw prewd te be for tNS Natly thsn eedtrs dte ate atd surileal trNeNAe of Metwes wltA Isrpd bMtt wlwa TIFL 0305420 
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ClGARETTE S.VOK/:V6 AND DOGS-AUERBdCff 6T AL in such sq mus zones had nuclear atypism similar to t seen in the acini. Giant nu- dei also me more prominent in the tu- mor foci. Conm tant with the more 9urid praaas found onl in dogs of groups H and h, there was an ext fon of tumor calls through the basement bnme into the underlying s,tcoma, a mpanied by destruction of at- veolar ar 'tecture and fomnation of con- Ruent tum r masses. This occurred iti 12 dogs, sonu of which had tumors of this type in two or ore lobes. Although the tumors were multi le, they were genen119 concen- trated in ne area. The tumor cells were bizarre wi giant nuclei; mitotic figuzas were p it and squamous areas promi- neM Calcifxs 'on in the form of rounded la- mellated, oma bodies was observed in a number f tumors, although not as fre- quently av in human lungs, as reported by Liebow.t In four with invasion of the underly- ing stro there was also in.asion of the overlying eura. . In no was ttwn evidence of inetesta- sea to the cheobroncitial lymph nodes or to distant 'tes. The fee ro of the hronchiolo-alveolar tumora bed previously are illustrated inFiglto Involv n4of a bronchiole and its prox• inilty to n plastic adni are seen in Fig 1, a photomi ph of a nonirrvasive bron- chiolo-al Iar tumor tound in nonsmoking dog N904a The tumor cells lining the acini are retati ly uniform in size and shape The n aee not praeni.rttt and, when viewed the miaroecope. the nuclei are fairly in staining character. The cells are t arranged in sheet-like forms- tion. Figttrea and 3, photamiaegraphs of in- vasive b chioloalveolar tumnrs found in smoking d p H8i6a and H878a, illustrate the sheet-Ii e arrangement of cells, variation in size an shape of nuclei, prominent nu- cleoli, and arrowing of lttmene of neoplas- tic acinf i©Ily found in invasive tumors of this t Figure 3, in addition- illuslrates t•xtension tumor cells to the pleura Fig- ~re 4 inuat etea invaa:on uf tumorcelle into ihe pleura. 765 Squamous Cell Btonehiai Carcinoma^ An invasive squamous cell carcinoma of mi- croscopic size was found in a bronchus of each of two group H dogs that smoked nonfilter cigarettes (Table 3. Fig 5 and 6, and color Fig I and 2). One was in the left main bronchus of dog H885a. killed after having smoked 6,210 cigarettes in 88i days. Serial sections were made from the blocks in which this tumor was found: photomicrc- graphs of three of these sections xre shown in Fig 5, color Fig I and 2 Figure 5 is from serial slide 55 which contains several serial sections. These serial sections were stained with hematoxylinsosin; the magnification is x 250. No basement membrane can be seen at the spot where the an»w points to a nest of col6s which protrudes into the underlying stroma. Color Fig 1 is from serial slide 56, which contaim several serial sedione, stained with hematoxylin..rosia The mag- nifimlion is x 400. The crrous point to the same neat of celh shown in Fig .5. No beae- ment mambrans is discernible at the spot to which the arrow points. Color Fig 2 is from serial slide 58. The tissue was stained with silver methenamine to show ttrore clearly the huemettt membrane where present. The magnification is x 650. Study. ing serial sections mieeascopi®I(y proved that this nest of neoplastic cells was an extension of the seme nest of cells seen in Fig 5 andcnlor Fig 1. A basement menr brane is clearly seen between the surface epithelium and the nest of reoplastic cells, but thete is no basement membr^se below the nest of neoplastio cells. ?A clear mitotie figure is present. The seoond squamous cell carainoma of microscopic size was found in a branch of the left apical lobe hrmechus fram dog 877a killed after having aaaked 6,135 cigarettes In 877 days. Figure 6, toq shows a section of this cancer stained with hematoxylbt- eoain at a magrti8nticn of x 250. The tumor extends below the basement rtsmbrane into the underlying ti%ve. F3gure 6, bottom, shows another section from this cancer at a magni6cadon of x 400. The surface cells and the cells below dtert have nuclei which vary in size, shape, and staining dtaracter, they have prominent nucieoli. An at,vpicsl mitotSc- 6ttuw is prexenk. The eells' ire' sheet-like in arrancement. Multiple Snger- Areh Eaciron Henlta-Vol 2r. Dec !9N 7-oO:?C)5-/8- TIFL 0305416
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-7- Ont de of the tabaceo induatty a reduction In cigarette eonaumption vouid hav ecoacol.ca7ly n•°libla effects and, on t2ie othen band, voitld probabl,y e economie S%3ai through ivcressed 2eogth of ]ife and a c¢t in Iast due to 171ness. Plirthermore, it is hard to thiak that money aot spmt for cigaaettes vodd all go into eaviags. It vessld most likal,y be spent or somethtag else; there am still matiy umsatisfied wants ia this cauntry. Finally eA ths eeoncrosle aide, a aatim vhich haa 4ust experieaced a forty b on dollar increase In gross national product cannct conceiroably have any peat diftieulty sdjustiag to a gisdual redacticm In ons aegment of the ec which, by the most elastic cemyutations, accrnmt for a total emrnmt of ecenomic activity tmder bea billion dolJaYs. Aed the added prodncti ty of paopls who live longer aad are healthier asut all be on the eo c glns side. Go back to the matter of cigsrette advertisiag, if the compaotes do not xt to consider the aatter of suapmdiag this aavertising, then ve be]i steps mnst be taken, ia the yublic interest, to counteraet the effecti eas of cigaaette advertising. We believe that this can be dome by requirza a clsarly-veaded varnina msssage to appear In all cigarette adverti ts aad 'at t]u sad of a11 cigaretts commercial• on telsvislon and radio Snaa Hsubexgsr hss a.IS'sdN touched aS this point. The Camcil has agpointed a laoslative eo®q,ttee to recomiend steps irhich we my believe to be nec ssary. 7 00210539 TIFL 0305452
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-6- Al1 era of this Crnmoil are veil aware of the importance to the satiaa'a conc=7.o well-being of such thiaga as ~obs, farm incou, profita and taxss. We are aware that s substantial reduction in cigarette consuspti - for vhieh we ars uorlting -- would adversel,y affect all of tbees. er, ucdsr ao ccoceivabls eircumstsrces is the tobaeco industry going to cllapse overnight. In the firat place, we are tal7dag about suspenei or restriction of cigarette psometion only, plus edueational activitie desigaed to reduce cigarette consmption. In Itsly rrhere cigarette advertising vsa banned by govermeeat edict, cigarette sales gained at a SMLlLftr rate in the first year following the ban. Io tEs two years prece3Sas the ban oigarette salee in Italy increased 6 percent each year. In the at year fe.Llovtelg the ban, they Iaoreased on7y 1z percent. This on xas not necessarily a direct result of the ban, but it is one of the few clues ve han ae to vbat might happen if there were a snspensi of Mgatette sdnrtisiag in tMa cocytry. Oae aflght expect the effect 3>n thSs conatry to be greater -- becauae both the relative extent and rela n.effeetiveWss of eigarette advertisiDg In the United States are prababl4,at a bigber lavel than they were ia Italy. $ any event, cigarette sales are going to deClease slowly aod there syLonid be c®siderable time for all those engaged in the indnscry to sake t. T OOL011338 TZFL 0305451
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eave mi dovelop by just calling o?ea1Y, lions of livaa. 6ut the Yole of tha taacuot vill not ba :ylip 4 vntil the echool aL2iaia=tian e:.courcdaa it--cncousa;oo i: ra: allowiag a Icaal voluata.y healzS agc~c~ to cSov a fila, b-.:= by togatSem t.tie £aaulty cssd cha acSSaia~asiaa to diG.uao. aad the p:oSlem qad itn solu':oa.
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.... C!_::i t:.o Ca-_.i''c:oe a= ~i3 : L•ote__ v; aa:. to L_i_.. ~. _'se Cc.=^_ittae consii:ars -LLa aoss_u_' _, ':o m.1Se si'C.1 cP.lcIIlLY,o9s, but it __?6_'ves o o=ny assuaptions tLat the Cc=ittae fe<t tLat it \ ~ ;oa13 not ..E=--yt._tlis,-ttat it a:1_i ha Lis . _s=aad:-o _s~ :t ras =n':oraaC /. "_~.'Tr y, 'J..^s -r3s1L..nL` JOi=on saca tte . C°70-t and i"! ~.'.3 Las, 5:::at !:3s 13._s r31ctioE!? Dr. ieSry: I Ci'JII!. ICP.Oi~7 C''Aettle'S P_^e.SiGCntuDL`.IIs6n- 'as .--9= the reyort. Copies La7e D32i sent to t12 L'.;? °.9 iLCl2S°. 6•aestioa: Dr. Ter--, I could IiLa to !-2-17e Dr. r:.'ett9 Cl,23'3'~J for Se i:.e ~S^'L'.~°- ^°-^ t<'e t"~iJ t.^.teCBDlls. CiG'dTette G=ol:j.=~ is a cause o_ cancer, n-nQ here is a c-susel r2lation5ain o2ct^aea Ci-.ratte =_ao?;iaC a.nd aacer.. I eoulu ?i3:e to get. tt: t c.:1e distir.ct?y czear. Br..Dt:=d3tte: PerIL^.7sID.."'.ter aL•SIIEF t3i.s ior ., yse2P ?m-ther than for the Co=nittae. iaere'is a br_e_ H H O:;siC:o•_"at'_oII. 7y: here ol' tr;iis to establish a C.Ii311 ~ r `~ 0020531 el=t=oasri2 and ,he so-Ca11e:i criterin io> the ;;u3gzlente o w ehe-a p e Ccm-.itt2a felt/cI±=re cas o:Iy a ntatisticzi assoc_It:oa v+ - ,a ~ ,p hat tilsep croulfl not co :c'iucie that t-e.-e •s_3 ;L causal cl..._caoaip. TL•_s eean= tI:•_rr acy =e.a caussl _aln._ nst3~,
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12, ?54 Procredtngs of fhe American Association for Canaer Aeseaxh y ~[A , ti a 3 cent we,e given injectiom of _0 X 101 Krebs4 mcita tumcr cvlls, they rhowed a smaller incaeare in frae tumor cell population at 7 days tfmn did normal tumor- beoriot nuee (OOS.g f 413 X 10- veeaus iSg.O t S?.4 X 10` ceLLs). Thus, in the diabetic mouse, along with increased peritoneei fluid glucoss levels, ascites tumor growth is slowed. DITERGr1T PE\-ETR.'„YCE OF POLYDAC. T1ZD1 L1 3IICE. Lsowas C. Srsoxo. (Diologi- cel Station, Roeweil Parl- ]Gmorial SPst.. Spring- sille, S.Y.) Six sublinn of a single outwss hetweeapolydectylia and C57 female., bseed upon maternal age at the time the oHspring were born, have been coutinued.Only data on polydactyl'u penetrante ate reported here on the earliest maternat age demnt and thatbetween 101 and ?00 days of age. Ia the F, and F. generations penetrmce of polydaet.'liawaeidentienlinthe twosublinea(8.49 pv, cent compared with 3,47 per cent). Penetrnnce In- creaaed at identical r.tes up to the F, generation. Diver- gtnee appeared first in the Fr generation and brame progrenively ineeeaeed iry to the end of the esperimtnt in the Fu. Penettaace in the F~rFu geuentions wes 7537 per eent in the early litter descent but nnly at.9b per cent in the other materod age deaomL The .tigai& canee of this obtarvation to onoc:r researeh liw in the (act that similar tnnds btoe been observed in nueepd- bility to chtmically, iinduced tumore. The biological na- care'nogms- tun of these trends is disevteed in order to determine Saturated soiutims of tobaRO tars or mlutiacs of bow much or how little morphological and physiokgical characteriuties have in eomamn with the origin of vori- ous types of experimental cenar. dltemstive esplaoa- tioos of this divesgeaa in the penetmnce ot a moepho- logie.l charneter will be distassed. TH8 EFPECT OP TRidZE.'1E.4 ON TEM G80t4T8 OF A 1:4RIET'Y OF MOUSE, RAT. A.MD lil]L- STEB TL7I0R3. S.zctarm Strorva.. (Div. of E>perimental Chemother.py. Sloan-Kettcring Inst. fur Canm Reaeach, \ew Yark N.YJ This report conssb of obtetvatiom on the e9ects of II,9-dimethyl-l-pbenyl teiesm4 9,9-dimtthyf-1 pnitro- Yqelohatyt.M1metbyl-l-p•tolyl phmyl triasena and eri.z.ne on the growth of sirt..a anlid tumos of the moore, four sotid tttmcu of the rat, ona aolid tumor of the hamster, and three.aedrea tumuu of the monx. In geneed, the &st in4speritos.nl injeetiomof mmpouadr' wera gisee 1-7 days after tmam transplantation, and injectiom wese caatfnod for 7 dye. Daily maamns tolsrated da.es o! S0 mg/kg ct g,9- deeethy4l-pbanyl triwao bad a deatruative effect on Crabb hemstar nreema and 1Gehe 3 aetitn cucinoooa; & marked inhibitnry effect on Saloo® MA 987. Ebrfieh caldnom4 botb rolid and aetites fotms, Adanon+cino- ma E 0771, Carcinoma i0gd, Rfdswsy osteogeaio snrw- ma, +3Iecea lymphowtcoma G6ema >te, and Sueoma IeO.rcites tumor,a moderauinhibitory eHectan SGyo- no odeaoeaeiaoms. WagtsQ osteogeeie sneoma, Gard- nar lymphowtcoma, and Walker etreiooenreom. Pbg; a slight inhibitory effect oe S.reoma 190, Sneoma T 441, Hashford cueinoma 6g, yewi. Inag enacinoma, aed Fksner•Johling coreinoma; but no iubihitory eBeR oa Lewis bladder cojeinnma, tLanliog-Patrey melanoma, Jensen sareoma, rad 11:urpb^aturm lympborertoma, The tQceta of 3.9.dimetL~,-f.p.nitropbenyl triasece (460 mg/kg/d.y) on these di tumora wera esaential{y similar to thote of 9,Sdimethyl-l-pbe4W triasene. S-CyctohezylS-methyl.l-p-tolyl tnasene (SLi0 mt/hg/ day) waS much lev effective. It had a destructive eHeot on Crabb hnmrt.r euwmat a ntoderate inhibitory effect on Caranomn 1025, Ridgway osteogenic snrcvms, arsd GGoma gE; but there was almaet ao inhibitory effect oa the other twenty tumom teated. Rerults obtained with thete sad other triasenet on eh r eyecttum wilt be presented. EPFECTS OF SATQS.4,TED SOLL'fI0A5 OF TO. S!tCCO TALBS A-\'D OF p,10-DIdfETHYLI.9. sE.zA.v~THRACErrE ON TEM gUrSTEas CHEE$ POIIC& E9w.an J. T..aas,e Z Go- esat,e A. C. Rsrozz& and Sswtrtsr C. Scoatxa. (Depta of Eipeeffiental SurgetT and Patholop, McGill VPiv. Moatn.l, C.nad.) The cucinogeuio effects of tobeora taa on.the mooe. rldn hav. been reported by several inveatigatore. In thi. esperimeat it was attempted to obtain data on the eti• cinogenin Proptrtiee of tobnoeo tan in relatioa to a mutau membr.n., u eampu.d with a well Imown 9,I0-0imetby41,4-benztntbruene were app6ed 7 t®es weekly to thw cheek pouch mucon of ham+ters. lot a period of 14 montha. A atursted solution was prepaeed in chloroform, which was allowed to evaponte before the appiication. Iu a cuntral group of animale mm 04 skae was tned. In the group of h.mstera in which rtunted solution of mbarm tan wu ueed, nodulei and thicttening of the distal end of the pouch wae observed to develop attat 4-g mcathsof applicatioe, in es per cent of nnim.lr.ln someot these animals the nedalnrnotved eponhnewuo ly after " wee18: othen perairted until the taimale were seerifitW. H6telogieel ssetiom of pauehes beaiag palpabb aadules showed maeloed fib,eblastie p,oti/eef tioa beneath the epithelial surface layer, which was f». quently ulcerated. The newly fnrmd toll.g.naus tiretr extended for a condderabk distance m the mbmuwr and in maLy plenu tepiaced muscle or salivary gitad. ~pp~ wu that of marked and slightly atypied In the dimdbylbeeteatheaeet. group, tnmms wers obs.ned to devtlop in 10 per cent of b.mrtera. The tn- mara .pp.nnd to a.i.e from the sqaamuae epith.lium of the ehadr pouch muema snd were eLrriSsd ru sqYn. maasedl papillose" and necmom...CLIIVICAL EFFEGRB OF AC'ITt10S[YCIN D. CaArtoasa T. C. T.a,e hL Iam Litntrar. Huots W. Daaosotr,` and JtlnirY 1L RIIaCniYAt. (SleeM ICettering Inetfor Cancer Rrxueh and \Iemeei.l Center far Canev and Allied Dituees, Iiew York :f.YJ r6020466 PA -000466 - TIFL 0305364
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meen ~uld !;:tve to questif+n the etlect which the trauma itself might have hud iii I lte result. at~topx~ obacna.teona It ,s almost impossible to completely study the human lung in mv _•rent Qernil i living humans. However, detailed ea:uninations can be iunde in nut sies or following surgical removal of a lung. As ,t p:+rl:ologist, I maLe m any hundreds of such examinations ecen~ year. 3ome mees igatots clnim to have observed abuormalities in 'lnng tcsue that th y deseribe as "precancerous." These same investigatots alsn report ;m nssociation between ci~atette smoking and the iucidence ~+f N+ece nUn alities From these reported observations, they con- lude that ci nrette smoking causes certain reported chnnges ~chich prozie?s into wtg cancer. First of all let me say that no one can tell whether or not a lesion ,lescriUed as ` precancerous" will or will uot progress into cancer. In :mc erent, n ether or not tt particular fmding is to be termed -ptr ;+ncerous' i not easy to determine. For exnmPle, hyperplasia (m- ~rense in nu ber of cells) and metnplnsia (tissue changee) hnce :ometimes Ce a termed "precancerous." Neither of these States should ue considered as precancerous. Hyperplnsin and metsplasia is n fairly cnmmon findi m For example, over :0 percent of women over the age of 30 have sq amous metaplasin of the cervix. It has never been shown :md only inf uently sngges tesl that metaplasia of the carvix is a precsncerous lesion. }Ietaplasia is frequently found ia the lungs of older petsons Rhetiter thev smoke or not. Calluses o our hands, for example, are hyperplasia. Cancer, ho.v ever, rarely evelops and no significant assoctation between calhtses audcancer as been obserred. Metnplasia nhich has been reported in the bronchi, occurs com- monly in th trachea-or windpipe-but, as nored earlier, hncheat ;nncer is e~t mely rare. >Innv obse ers, including myself are tmabie to confirm the reports that signific nt cell or tissue chanr,~es occur in smokers more fre- nuently thn in nonsmokers. Cettamly there are smokete with no dtanses and nonsmokets with changes. I hare exn ined thousands of lungs both grossly and microscopic- ally. I cana tell yon irom examining a lung whether or not its former bost had ]ted . 4. Conchtai The evide ce supporting the theory that cigarette anokinti cnnses l+mg caneer onsists almost entirely of epidemiological studies +rhich repnrt an a istion heteeen the two. These studies ate b:uedon deatU certifi atioas which are often inadequate, and there are many, umnv incon 'atencies. ?..nimal e riments do not support the theory and probnbly do not offer m ch hope of doing so. Pathoiogi al and clinical observations are most uncertain to d:tte. As a of ail this, I-must conclude that cigarette smokin_ has not been p an to be the cause of lung cancer. (The atta hments to Dr. Buhlers statement follow:) -T00:'.0528
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page 2 .cient'ists of the vorld. A consensus ap nearly unanimous as say eonaenaua - about a health hasard is ever likely to be. This, hen, is the problem. Hhat abouC a solution? Unlike many probloma, this . one ha a very simple solutions all cigarette saokers should atop aad a11 non-s kers should never start. . . There eems to be a fairly pervaeive belief in this country that there ia little to be done for th. amoker; thae ue should concentrate our energies on that st oomplex of all targets-teeaagere and prr-teene. That is, the non. amoker, or perhaps, bettery the prevseoker. a have some serious reservatiooa .I about ,tais coucentration,of energies, but for the moment, let us consider it. There hava been a nuaber of studiea about teenage smoking. They vary vidaly in their ophi.tieatioa and thoroughoess. 8ut, in spite of shorteooings. certaia. quite lear concepta have emerged. Thara are fev emokers before the age of 10 or 2. Exploratory smoking increases rapidly to junior high school and fairly regular smeking begins to get a Pootbold by the 8th or 9tb grada. During high a hoolo the pereeotege•of regular smokers risas rapidly until abeut halt .' of the teenagsrs are regular cigarette smokers by the age of 18, ' . • Rates ~sty from ooe past of the country to anothare with more sod saslier • seokin in cities than in the oountry. Girla' smoking pattarns seem to vary . more f om ons school to another than do boya0e Considering the aanas separataly, sevara Interesting veriations appear. Girle start ®oking later than boya, but th percentage oz girls amoking increaaes more rapidly during high school so th t smoking is aa tommoa, or even c.ore eommone among girls as ameag boys by th end oP the I2tb gradee 2Moreover, Sirl'smokers seam less inkersatod in quitting then boys. r0020542 TIFL 0305455_.
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r _orcm Auobceh. afD. Ea<e Orange, NJ; E. Coyln Hmnmond. SeD, N<w York; Dacid Kirmmt. Emt Orviee. Nd; md Lmurrnu (7arflnk.l. dlA. Neto York 86 do90 tqlriod to Yroko throu9h a ImM. 12 degs (9roup F) tnmksd 81NMip, 24 up H) and 78 (grovp M tmaked mnllM taNU, and 12 ;9rdup t), hah ae ~unY non. d9arotw, 6i9ht dera (9roup N) naoer od BY dqq 878, none o/ the N dogs, 2 F 2 l doW. 12 H dogs, and 12 h do9a had and Iha roaek::n9 N. F, t, aM N de9s wor. Nenlnnalw bronehfeto-ale.oMr hunors EXPERIIHENT wen undertaken in primarily to determine whether 9rook- cigarettes equipped with an et6delt would be ks harmful t}uw amckins ter d/pueNee. Tbe problem of ex4apoa B atperimtntal 8riditlg in dcp to what oectte in man has been disctmsed, and Is of the ezperlment and Ardines in to mortalityt tauua of death, and NmlogF (othdr Nan nwplams) of pulmonary pmta•hyma h.va been fee ptmlratias Joy 28, 1970: accepted 4pL the Votenol AdroioLhatim Ho.pital. Saet H7 (Dr. AurVneh and Me Aitmae>, and the IA~ C.aew SodotY (OC tloemned ted MrsraaeBnk.N. b.fmo dr admNBe wtttae et th. mntoat Boud of Dtnxbnf ot tlw Amadm fm..r •. New Yodt, Ftb 8, IY6, and in part befos tlm en Diartw o( eha G3ef at the !79th convention at dfe Amerinn Mediol Aun. Cbieete. J®o 8t. 197tF t rqurla b V.MUM MladniaRatbe Roe• . gat Orange, N167019 .Dr. Auabtrh). wen lound Itr do9a of all M1n 9roupa Invafiee brellchktle.atWdR tUmers Mers foand only in It and h dWje In twa o/ 12 9mup h and 9recp H dogs, rapomtrdp, whteh died, and si9ht ol 12 9roup N da9e which wen kilted Ona extended to and four Into Ine pNUea. EsrtY inruin aquamaus cell ureinottu was found In btontid of twe a/ 12 9roup N de9s which wero kllkd reported.t Hrooehiolaelveolar tumors atN tar19 invasive bronch3sl ctrcinonwe ase re• ported here. itSafeeiN aod hletltaL 'fio materials and esperimentel ptoeodurea of this esperimatlt wor_ desmbed In the pt~ cedint pqi.r.t C18amttao used were at onc BItK•dp brand: non5ltor ci8frottes werm per parsd by remo.int the filter. Smoke from each 6ttar-dp ciptretto conlalnod 17.8 mt of tar and L17 m6 of nieotiore witlput the 81tar the cmuko contained 34.8 mlr ne tar and L88 mt ol niaotirte. Eight of 97 rracheoebmis.d m.4 beo8lo does n.v.r smoked ogeratn (group N). Durinr the &et 58 dqs, 89 doP w.ro entiMd to mabK two of them iUod rod eno was foutd to hm :r brain tumer and ws removed from the experi. ment On day 57, the remainint 86 mokine dop were dividod into tour troupo: group F (12 dogs) amoked filemtlp n9antn. therr after. 6roup H(2i (1er„s) end treup h(26 dnWt tmekW non®hr ei=aretteea: gmpp L(12 depl amokd ewndlta dpneNos but only hail 3* ~ Areh Enciron Heti(fA-Vrd 21. Dee 1971) i manr n h.:p'ler 'hm for 4~,ent7 d:3: 2 0l .ud 12 0: .wl H de .ero Ialle Autops dter dee Auted& by I.,de rolu unpofl the ribht: It WtCre: ..qMCt of dut(Y. TF ••'fre we wvws we rnu~heobm Ne Lmaa r . ~.hirh ai +tttion we in blotb (nm the Theea 22 s Iq foe bron evmoin.d 1 ••a3 eroy.i Soctiona (n incd mieee, (wn esrh wen eram NVfubtit t :mN1~ Tab(- L hl, the da• one orrnGt :he rttm•rber • the dog at tunmr, apd a'a fotmd. nuotber of . ing. Iadivid and deY cf I(ter day g7 ,(trr day E"- hnter o or t nne group I A2: H8926 killed the sar Ttrrrtors . •!ne. The n >ive and in,
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-8- em opttZiatic that it will not be long before people will no longer be eeeburaged to smoke cigasettes, either by the voluntaty suspeaaion of te advertisiag or by xedu^~+.*g its effectivsaess through legislation. t even beiore that happem, mnch progress can be :oade aad ts being vade. Wbat is now going on in Ca].ifornia aad uhat is being planned for the tu in that state, as we have beesd thd.s morntng, holdn maoh prcmlss. We are of the go.ing to have a meetiag this afteznoaa of representatives frva 25 29 etates vhere Interagecoy Counoi.ls bavs bem set up. TtrLs will be a aee to exchange iafozmatiaa on state pxograms and to help p]aa for the . Most of these state setivities are, aad will bep carried out ma1s7Y by volunteers. These are peopls deeply devoted to the principle that c people ahoolda't die and suffer unneeesearily, in large mtiobe , rahea this can be prevmted. I kaov that they are going to acc ah great things. m large nzbers of Americeas set out to help evea larger numbers of cans - tbrougb education, guidaace) and enceuragemeat - great thiags asy bamd to happen. W are just begiaaiag today the fim asjor meetiag ot the National mcy Co®cii ou. 9so$ing aad geslth. We sre e very aar argantation -- onlp a fer months old. We can teli you more abcut.aur Rxture plans and opea ous atter tbsse two days sre over. Aad we will be glad to ttaaish any ozm.tioa you naat. A the m®ent we aro- Just certain of one tdiag: cigarette deaths and ci e disability are largel,y preventable. cre are going to prcveet au ve c.a. T00Z05h0 TIFL 0305453
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APPENDIX C, ---- crntinuecl S+wJ+ Afr'wa <:on.rU Chile . RI Snlvadur Ilninxl Suies, N'hite IL+nnl Smtrs, Nnnwbile Niramgva I an: R ~:n enrrw . Venr..rIn • China Taiwan • Ih.nB KonR Isocl 1 nxm Philippinc • Cl.~llund crrm,ev. Fai. Relub. Aaslria Belginm Uevmrk I i~nL rvl Fraue Irtlvwl Ital- Nnrwny NetLnlands • Pol:-d 1'nrm8x) Gq;l.nd .nd Wnles °coJand Nonlrm Ldnrd SweAcn S.vu.erl.rd . C.~.M.invakia . Yeqosla•in Australin I 152 - 19:t Inlesline. exc^p1 nrh~n~ M I F 0-78 (15) 3 42 13 .98 ((31) 0-63 (40) )3.69 l )3 11.33 (13) l 69 (38) 0.12 (41) 3.61 (32) 4.13 (30) 3.06 35 4.47 20 6.49 125 7-21 (233.32 C131 2.08 (37) t.22 (39) 9.96 17) 10.35 16) 12.24 )9 3.13 (34) 13.60 (2) 5.19 (26) 11.53 ((1) 4.48 (27) 7.58 (22) 12.70 ( 17 8 11 (20 8.27 (19 10.86 (14) 4.23 (29) 7-74 (2D 11.02 (10) 16.14 11) 13.06 (6) 9.57 (18 1L37 (12 7.10 (241 2.19 (3(,) 11.85 (11) 15.34 l(I) 4.73 27) 0 85 (39) 12.84 (7) 11.62 (12) 2.77 (35) 0.39 (41) 3.75 (331 4.48 (29) 4.31 (30 4.28 (31 4.98 (261 7.69 (22 :1.16 (34) 1.65 (38) 0.81 4U) 8.95 17) 9R26 U61 12.36 (9) 2.69 (361 13.60 (4) 5.60 (25) 10.19 (14) 4.60 28 8.13 21 13.12 5 7.58 (231 8.36 (201 11.60 (131 3.86 (32) 8.63 In 11.91 10 15.19 (21 12.73 (8) 9.35 (15) 8.61 I9 5.70 24) 1.97 (37) ISM1 Reunini M r 4.21 (25) 6.80 U 13 2.19 (321 0.18 (40) 5.40 (201 4.71 ((241 0.31 (39) ) 2.08 (33) 1.89 (34) 1.70 35 2.39 31 4.73 3) 3.32 (28) 4.74 (22) 0.91 (36) 0.1014)i 8.16 (8) 9.90 l( ))6 9.19 3 3.56 27 11.53 1 5.64 (18) 6.82 (12) 0.62 (38) 6.73 (15) 7.43 (II 5.29 (21 5.57 (19 6.79 (14) 3.26 (29) 3.74 26) 9.25 2) 8.9A 4 8.11 (9) 6.40 i )6 7.66 10) 8.95 ( 5 ) 3.0 (.UI) Ne. (calnrd 33 (5) 14.04 ( 8.36 (7) -16U The ligu+e. in ( ) shmv rank order. 161 162 -- 163 UrYn. Lung, bronchus uod vacho F _ M - r- r M 3.45 (19) 2 83 (lfi) 0-2 22) 36.71 (12) 6.52 (9) 4.30 (13) 1.83 (271 0-25 25) 3U.83 (19 4-73 (201 2.18 (32) 1.64 (29 0.25 (24) 13.83 I30 4.69 (21) 0.40 (l9) 0.29 (401 0.72 (36) L29 (40 0.71 ( 140 3 36 (22) 2-04 (19) 0 22 2 (27) 36-86 (I11 5.83 (15) 3.38 (20) 2.56 (17) 0.32 1R 37.12 (101 6.09 II 0.96 (35) 2.02 (201 0.54 5 6.50 (361 3.57 32 - (41) 0.62 (371 - 41 0.40 (41l 0.51 41 0.91 (36/ 1.50 (321 0.47 (7) 5.44 37) 1.94 38 1.32 (3M 4.03 (61 0.52 ( )6 10.95 331 4.05 (27) 1,61 (33) 3.43 (12) 1-57 (1 ) 12.92 (31) 5.99 (12) 2-43 (30) 1.47 734 0.55 (4) 8.88 35) 5.95 (13) 2.90 (25) 1-86 241 0-31 (19) 29-80 201 14.57 ( )1 2.37 (31) 1.83 (261 0.22 (26) 70.83 5271 6.75 ( ) 7 3,46 (la) 1-52 (31) 0.32 (17) 12.64 32) 4.46 (22) 0.65 (37) 0.46 39 0-30 (21) 3.99 38) 2.12 (37) 0.03 (40) 0.12 41 0-03 (39) 2.13 39) 0.85 (39) 508 ( '8 1.99 (21 0-15 (34) 40.30 8 5.15 (18) 5.67 ) 2 3.80 (9 0.18 S32) 49.39 6 5.70 (16) 5.64 3) 4.20 (4 0.26 23) 46.7'1 (7) 4.41 (2 )3 2.64 (21) 8-84 ( e) 0.36 114) 35.73 (14 7.15 (S) 6.79 (1) 1.22 (35) 0.21 (29) 35.84 (13 6.57 (8) 4.46 (11) 3.70 (10) 0.15 (33) 60-72 (3) 3-77 (30) 3 70 (15) 10.16 (1) 0.38 (l )3 25.55 (25) 3.57 (31) 0.57 (38) 3.90 (7) OAI Oo 29.30 (21 5.54 17) 4.89 (10) 4.17 1 )5 0.39 411 34.00 (17 7.39 4) 3.62 (16) 2.17 118 1-13 ( 2 2a.88 (22 7.01 )6 3.19 (23) 5.34 (2 0-31 (18) 21.57 (23 4.34 (24/ 3.10 (24) 0.62 (38 0:05 138) 13.89 (29 2.57 (35) 4.38 2.49 (12) t28) 1.58 2.84 (30) (15) 0.21 (30) 0.30 ( )20 51.12 26.65 (5) 24) 1.39 4.25 (33 12 5 1 2-72 (26) 5.05 (3) 0.44 (B) 10.09 34) 2.19 (36 5.42 ( )5 1.94 (25 0-35 11 )5 67.72 (2) 9.70 (3 .,.54 (4) 1.9a (221 0.39 (12) 75.55 ( )1 11.44 (H) 5.30 (6) 1.96 31 0.78 IB) 39.49 9 6.30 (10) 4.12 114) U.64 361 0.01-( J40 16.44 20 3.78 129) 3.53 (17 3.17 (14) 0-12 135) 33.39 Ie, 3.28 34) 5.12 ( 7 3.19 (13) 0.22 (28) 56.41 )4 5.92 1 )4 2.44 (29 3.62 (11) 0.44 ( )9 21.78 26) 3.87 28) 2 1 76 28 0.20 (31 34.58 (16) 4.19 (26) 4.94 9 1.47 (33 0.08 37
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! LISaAftY ~ 'S017IIOC0 I.18x.1CL'C8. IIIQ• CIGARET • LABLLIt;G AND ADVExqTI3MG HEARINGS aerosa T= co°fIT'rEE ON Co`„IIIEItaE Ui TED STITES SENATE IGHTY•N7.~TFi CONGRESS FIRST SESSION ON S. 559 and S. 547 BILLS T REGULATE LABELING OF CI6ARETTES AND FOR OTHER PURPOSES . PART 1 ' Hd.RC 20- 23. 24. ?S. _9. 30. APRII. I AND R, 19&S Serial 88-d 7 flW~U55A PA1nt#d ter tM mm of UN Commithw on C~ I II.S OOPtR.IAfSVT PELVTLNO O!/!a' IYYI R'.1$Ii[NCTpN : 1203 r....~. w.y. s..e.a....,.~.,. d e..,...e.. u s. e......... a.ru.. oem. TIFL 0305466
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5idtaria usually ba fawe prograo The ree smoking of reas It took immuniz attempt goal to would a fruit i out a I non.ata and beh are cha element had the relate wdth altars as possible over a period of time. Meaguremenc of aucceaa or failure meana a before and afcer quaetionnaL-c and the hope that thera vill ~ smokers at the time o£ the poat-progra.n catharsie. Many o£ these ~ are pl.no.d aod caraied out by the .cuLence ehemaelvee. . Its have been discouraging. They range from a decrease ia studant ' of a few percentage pointa to a tuofold increase. Thera are a.nVZbar s why we should not be too diacouragad about these early aLte,mptao an enotmous effort for genjamia Waterhouse to convince people to be d against amaiipoz. These first afforta, etu, after ail, "ea:ly" and we are learning fast. So produce behavior change is a diLficult achieve. To produce a change in attitude about smoking or smokers ao be a positive accompliehment. A chanae in attitude migbt bea: a few years when the ceenager becomes a parent; buys a house and takaa fa inaucaaoe poliry.Another problem is that of trying to meaavra a.' : 1e change. It is apparent that teenage smoking attitudea, beliefs :~ svior have been changing rapidly in the past 10 years. Noreaver they nging differently for boys and girlo, To measure the effect of a aaw, ' we haw to be able to predict vhere tne change would have taken us, nw elemwt not been introduced. .: .innl problem in meaauremant is to this, The fact that we are iatRreuted in bringing about a cbanga t the subject Smows that we are intereated in bringing about a caaagee. the .xiatiog pottsta itsalc, iadapacdaat:y of toa tachniriuao w usa. ~`flIJ2p545 TIFL 0305458
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-5- T"cere are ~nY things that people do for their ea,{oymsnt aod pleasure which are not goo#~1 for them; which, in some cases, detract from their longevity or cause their il2ness. But tmlaes such activity affects a hum proportion of emp those in them, then they shoald not become a mtter of public cmcera. Based evidence accttmalated up to this point, I woaT,d say that cigarette ldag is the CDly fOra of the {lee of tobacco which JSL9tififs at{y kinfl of res ctive actiea.:" Dhay ople say cigarette amakJ.ng is like driasing. But it is aot. Only e- people are very badly affected by drialcing whiskey, or other alcobolle beverages. IReeeatly Rutgers lhiiversity, which has for years cenduated !~'"s studi.es of aleoholim, reported that only 10 percent of people who drink coho]Sc beverages suffer any ill effects theretrcw. If we ought that cigarette smo14ag edversel,v affected the health of on.Zy 10 perceat of those who amoked cigarettes, we wouldnlt be here this morniag. It is because ve feel certain that coatiauad cigarrette ®olCng adversely s eets the health of a ver3r larae proporticai of those vho smoke cigarettes, aad.canse the pr®ature death of a substeatial proportioa, that we believe peeial affi unusval steps ehovld be teken. Aud that is why this Ccumeil vas formed in the first place. We be eve that it is amatter of fact, not of opinion, that eigarette smoldag c titutes a to MIM heelth hazard, for6ua4tely not matched or even app by any other health hazard; aad that it must be recogeized and dealt with accordingly. TIFL 0305450 / 0020537
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pago 6 Current school activity ia cancencrating oa the plrs¢oiagand developmant of . units o smoking rithin the school curriwlua utilizing the wide variety oF materiai presently evailable and being developed. Material an the physiology, the phy ology and the psychology of omo.aing Ls being developed for-fcctual. ' presenta lon. Dcmonstrations, euperimanta aad audlo-vioual aida are aa®oaly • used, 0 s particularly interestiag dave:opment is the diacuasion and dissection of adver ising by the students. ' Theee ax not new ideas. They are not even secvre fror attaok. Sume have questi d the value of independent units an smoking and health as distinct .. fror oth r areas in health education. What after all, are our goals ia health aducatio T To create inwture and amateur physicians with a fund of l,mdaquats . kmvladg to use all their lives? Or is the aio to teach•children chat their : actions 0 , indeed, have lasting effects upon their lives, that ill-hulth can be c used by their aetioare that what they do aad how they behave can me'r.a a differ nee to their health, and that thay have a responsibility to maintaia : Smoking epreseate a wlque health hamard, providee us with a good cxampla of behavior health interaction, and gives us a good opportunity to explare our , ability o influenae behavior ch.nge. Tae uniquanase of the harard is ralnted to its p rrasiv.ness. ita impact and damage, aad the uselessneso of the causati ageot. :t baa been aatimated that if the smoking patterns of 1960a196~wera to ¢ootidue, over 1,000,000 childrens now alive vill die unaecesa~~~uuueeeily of lung cancer aloae. If we ooaaidar heart disease and reapiratbry diaease, the nurber affacted could be four or fivo timaa w hiZS. . .. ... . . . . ~ r ~. . . . ,.. ~ TOO: U546 : TIFL 0305459
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148 ~ ClGARETTE S.1fOK1.VG A.VD DOGS-HAA(3fOND ET AL before y 876, two had gained weight, three had loat Neight, and seven were close to their starting eight3. Of 12 group h dogs which died, ei t weighed less just before deeth than at t is start; one had gained weighR and three ha maintained their weight. Of 4 dogs killed after day 875, 21 weighed ore than at the start, 17 about the same, d hvo (one group L and one group H dog), ass than at start. Fin ' gs ln Lung Parent9synu and Pleura. -lhree dilferent grades of fibrosis and em- physem aee illustmted In Fig 1. to 3, pho- tomicro aphs reduced from a mengiftation of X 50. Be©use of the magniftcation, only a small p lon of each lung perenahymsl sec- tiom is own. Grading of each section was based u microeeoPic examination of an atm uring atout 2 x 2 cm. In y instances, all seven sections from the sam dog were graded the same in te- spect t a particular type of finding and there ee no instances in which the seven sections Irern a dog varied greetly. Beceuse of this istency, in Tables 4 and 5 the 5ndings are shown in terms of all sectiom (rom "Eed groups of dogs rather than for each Individual dog. Figure 4 shows the findings in greater detail for fibrosis and Fig 5, for phyx,nra We 11 discuss first the findings in group N. F, L, and H dogs killed after day 875. Fib ie.-Fibnsis wae classified in six grades, through 5. Figute 4 shows the fmdings in dogs killed after day 875. Each dot on t graph represents one section. The seven d ts on each line represent the seven sections of pulmonary paratahyma from a part' dog. The sections were read indr pantiutty without th.•lmoodedge that they came 1 the xme dog. As shown in Fig 4, with t exoeptiom. the seven sections from an ' dog showed the seme cr dow to the ~ade of flbreais. For esgmple, there no instance in which some sections were gr de 0 or 1 and other sections wae grade 3, 4, or 5. Eve section fr.e nt the 12 group H dogs reven] a muck higher degree of fibtasia than an section from the eight group N dogs. Every fte of the 12 gtrup H dogs had mo» seciion of grades 4 and 5 than any one of the tan group F and the ten group L dogs. On the average, sections frorn group L dogs reveled a greater degree of fibrosis than sections from group F dogs. The diSerence between groups L and H is highly statistically significant by the Wilmr. an hvo-tafl raltlt sum test (P < 0.0001). The difference between groups F and L is also statistim0y significant by both tests (Y < 0.05). The top part of Table 4 shows the same data aaxmbled difierently. For each group of dogs the percentage distribution of sec- tions is shown by grade of fibrosis. The per- centage of sections showing grade 4 or 5 fibrosis was 0% for group N. 53% for gtoup F, 12.9% for group L, and 91.7% for group H (Fig6), Emphyseeu.-Emphysema was classified in four gradn, 0 through 3. Figure 5, similar in format to Fig 4, reveals that every section from group N dogs was grade 0 while all but one section from group H dogs was grade 2 or 3. Every one of gtmtp H dogs had mme sections of grade 2 or 3 than any one of group F and L dogs. On the average, sections from group L dogs had slightty more emphy- sema than sections from group F dogs. The differences between groups H and F and between groups H and L are both statis- tiwliy significant by the Wilcozon rank sum test (P < 0.0001). The differenee between groups F and L is twt staatisti®]ly significant (P D 0.05). Table 4 reveals that grade 2 or 3 emphyse- ma was found in 0% of sectionl ftvnt group N, 12.9% from group F, 24.3% from grvnp L, and 98.8% fmtn gmup N(Fig 7). Pad-Like Attaciprteats to Alveolar Septa. -Pad-like attachments to alveolar septas wete faetd in over half the sections from group N, but none wes above grade 1. Gradr 2 padli/ro attadvnenta were found in 0^% af sections from group N, 22.9an fran group F, 48.6% from group L, and 97.6% from group H (Table4ard FigB). Coosiderfng individual doge, the diderence betweer, groups F and H and f»twaen groupa L and H am statutimlly significant by the Wtlcosun rank stua teat (P < 0.0001). Tlte diRetstce between groups F and L is afatisti- cally significant (P < 0.05). Thickness of the Walls of ARerielet.-The walls of arterieleswere of normal thiclmese in all the sections (rom group N. Thiclauss nf grada 1 or 2 was found in 0% of sections Tal G+<e et ca nn,otaega n>. at uNan~ • Groue M a. from group from group (Table 4ant Cwuiderir ferences beb tween grotrt significant h fP<0.000t tween gtoupv Thietmex the pleura 30.4% and f etoup N. T. (nund in 0!';, from 'roup 00,5`9 from.- Arch Enuiron Heefth-Vof 21. Dec 1970 TIFL 0305400 j I 7- 0020502
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ao CIGAgbi18 S'IOxINO IN Tl:B U2CIt SC80GLS* by Daniel lko,rn~, Ph.D. Chief, Speeial Projects Section Cancer ControL Progr®, Division of Chronic Diseases 8.(o#a plungieg into a discussion of the taenage smoking problea let us take a feM~ minutes to review the health hazards of smoking. te from the Surgeon General's report raleased in January of last years • "Cigarette weoking is associated with a 70 percent incraaaa in the ' ags-specific death rates of m.les.... "Cigarstte smoking is causally related to lung cancer in men.... .. "Cigarette smoking is the moat important of the causes of chrecic bronchitis in the United States and increases the risk of dying from chronic bronchitis and eaphysaaa.... "It is established that male cigarette smokers have a higher death rate fram coronary artery disease than non-sanking malea.u This La by no msws the end of the appalling list: peptic-ule•rs, cancer of ., .. thh uth, threat, esophagus and bladder, traffic accidents and fires.ara all ; rel ed in one way or another to smoking. 7Aerson Yoote, Chairman of the Nati~boal lnteraganry Council on Smoking and Health, haa stated that cigaratte em• ieg is responsible for at ieaet 125,000 prematura death• this year. That ma • that every 4 mlautea aomeone in the country dies prematurely because o! i• cigarette smoking, This is indeed a national catastrepbe: states•ats and conclusions are not the far-fatehed tbought• of a few wild-eyed ralonar•. They represent a consensus of opinion amoeg ths *Pr sentad at the .eeting of the Aw*rican Aasociation of School . A inistr4eqro at.Atlaatie City, Neu.Jsrseyr 7ebruary 17, 1965s r0°~0s~i ~ I~ - VVV7V 1 I . . '~ •= TIFL 0305454 • •
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p:.;e 7 Raving pent all of this time on fa'irly ca:o $raund, I would li':.e to tt.:3 now to more discouforting subJect--ourselvaa. I noted earlier th.it : h;.d aame ra ervationa about concentratinS our eaorgiaa on the pro-amcaer. In.tSa first p aoa, tho.. 125,600 pco?lo who vi11 d!J pra.atursly thls yoaz aa a' result f their cigarette smoking a:a =t taaaagerst Tney are adui:a .:ad . those a e a lot of people to write-oa with .:n idle etatc~zant. Sacoadly, aomethi can, in fact ba done about thao. Withaut anybody really doing anyth to them except to provide them with ioformotion, about 12 percaat of the eo who vers smoking in thia couat:g ia 1962. hava quit. AatSar tSaa writs t e adult off as hopelesa, we ::e, :a :.:ct, atudying this very Cozraa phenome n of quitting so as to c,:adnito t8a e~:iciency with vnicn ::aa ch:.aga can be rought about. Finally, and rmost import:.at to our diseuasioa tod:.y we must re ognize that many adults serve :a esemp:ara to youth. ?arenta, physic •, dwtists, others in tha haaltS proaaasions, miniaters, athlataa, aod, ia us not forgea, the teachar. . SSe sea with whieh we ignore this ?l.aituda ia ironically humorous at tizas. Almoat 11 of the 36 state medical sociaty reaolutians about smokiag :ingla . out you h smokiag os their prime concr.a. Almaat without exceptioa inta:aveaey councils oo Smoking and Healtis, vhile ataaa„ .'saC they are conca:..ed chiefl7 with ab ldrsn, haw no twnagers in attondaaca either as membars or obcarvarg. , :nosa uth groups which are mamibea, c:a uaaaly repraaeotad by sa adc:t, As adul x5 sit asound ia otc pl:.:.atag coc.cila tad acy, in afface, "Sat'a" . go af th.'kidae but le.vs mo out o: thic"I hcva eyouES :oub2na al:ezdy." 3esidss as evezybod~;ewrrs7 you ea': :o cythL: ~9Ki adulto 7 00Z0547 TIFL 0305460
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CIGARETTE 5MOXING AYD U005--AUERBACti Er AL 767 iated :herv hiole ~~Yh i the. lsof ;rting ^ary uded .ir tu- J~s of r. our - hron• de- - i'lID[e . rcgen_ - oread . have . . <illed-. cd a t.he rs, has not been found in any rasive branthiobelveolat tumors in the alveolar t eight nonsmok- orgare will be studied like arrmge- o(ourd These more inte iveiy later. A st,eet- micrvscopic Expecimentally lungs of dogs two (Fig of I1. our ProTbstedgroup of werauced of Tumors in ment of Is was an extremely frequent size and were not found by gmsa examina- e tumars of smoking dogs and in the more malIgnant finding in the more frequent forma L amtas that squamotzs meta- Dogs.-Sq.zamous bronchi in dogs has been produced by the plasfa in ronehiolo•alveolar 'urnora in hu- m znapplir~tion of tobacco smoke cnndansate.rs , having been present in zn bein is rare, of h' 20 rases Clarke and assotiateazs administered PuO: in an aerosol to 40 beagle do~s. Five Carunama.- f ten dogs which euwived front 29 to 56 .~ly saviw Bronchial fnvasive uemous cell corcinoma of rnicro- of size was found in the bror.:hi of two mantha developed bronchioloalveolar cxrri- average aga at death iug tion. cell carcinuau of the 17u Wmar[• were accompanied by dogs whi smoked nonfilter cigarettes. nwna. extensive pulmonary and pleural fibrosis. Theee' two caroinontas were indigtinguiah- The microscopic findings of bronck~ioloal- able from many very small cazcinomas which we have observed in bronchi of hu- veolar tumors with subsequent malignant are in many ways, similar to the man beia who smoked cigarettea.r= character, tumors in our series. The Natn (kcuairg Pulmonary Ttiuncn more advanced ertensive Pleoroorphism of the ortb, the in IIogs nary tumors in dogs have of giant nuclei, rnitaeea, invasion of been deser d by several authors. The prev- prerRnce the underlying atroma, and, finally, invasion alence va ies fiom02% to 0.6%% at the pleura, are comparable in the two of sulopey.u. I Nielsen' tound the sWdiea (hr study differed in that we did not observe metastases to the erariteobron- fOr dogs with such tumors The to be 9 yee chial lymph nodes nor did we find distant of tt]e dogs with lung cancer in average a metastases after 875 days of smoking. eported by £.:odey and Craigz% the serirs and the youngest dog Was 7 was 10.8 y ars, years old. The lattr[ authors stresa that Conclusions carcinoma of the lung is a disease of old dogs. and ppears rare in those undar 7 Noninvasive bronchioloalveolar tumors y~ of aq were found in some dogs of all our groupa, . A revi including dogs which did not smoke ciga-. of the literature by Broday and C:aigu ' rettes. However, more surh• Wmors were losld 103 rsnix lung tvmor; 68 of which were found in smoking than in nonsmoking dogs; . adenomrcinomas. Jubb and KenziedY' significantly more were found in dogs smok- - on the other hand, state that 78% of pti ing nonfilter cigarettes than :a dogs smoking ry tumon ofthedogare bron- lar tumors. Tumora may be chiolaralv filter-tip cigarettes. ~t`e conclude that the multicentr smoking of cigarettes greatly increases the in one or both lungs but occur typf[af{yy probability of development of such tmmn soFitory nodules which arise in the perip in male beagle dogs and that smoke from o/ the diaphragmatic ]obe. These filter-tip cigarettes of the type used in this _ n grow•by'eapansiaur and in- filtration:- study is less potent in regard to tumar pro- istokgiceily they are acitnr tu- mors of ra duction than smoke from nondfltar ciga- !r benign appearance in Whlchh grow rrminly on the welEs -- the napp cely rettes of the type used of the al Invasive broechioio•elveolar tumors were.. . i Only a small proportion of. tarmcies metastasize. The microscopic s•u~ . found in four of 24 dogs that died after 626 . appea to 753 days of smoking tr,ny nontLLtar ciga- ._ of canine hrmon described in the litera uzettes and in eight of 12 dogs killed aFter 875 is similar to the least Acrid of the nonin days of smokfnS nonfilter cigarettrs. No in- 've tumon observed in our so- ries. -- vasive tumors were found in the other ght of the rarity of pulmonary In the1 groups of dop i nonsmaking dogs, dogs tuznonr; in :moking filter-tip ci;arettes. and dogs which dogs asxPOrMd in the f[tem- ture,z'•z'•zr we were surprised to 8nd nonin- smoked half as many nonfilter cigarettes as AreM L'nuven Heelrh•-Vu171. Dee I9i0 ~ TOO.,O.~w~ TIFL 0305418
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paae 4 in thelriak of a heart attack? Do we tell tSem t.Sat it ia socially Saaatyre and a rign of veakneas to anolu--chat only sheep smRai Ae ara in rather a naw eroa in amoking oducation. L'alika trying to moavatc people to do acmethiag once, liKa getting a chaat x-ray or a tatnaua cSot, and un ike tryiog to teach children to do aesatiiing always such as 'Sruao your t eth aftar every maal," we ara trying to perauada peopla to NOTA do aomet forever, go old techaiquaa, vai:e not neceasarily invalid, muat be atu ied carefully before we place too much faith In them. 7inally. the ; very £ et that teenagers are avore that "vs^ aa adults ara tryiag to cbanga them, :o study theo, to "manipulate" them makae it vary difficult to ?laa and evalua e a program that ia meaningful. In the Portland, Oregoa schools, six years ago we studi.d £iva different typaa . of app oachs conteoporary aapects of amoking, chronologiully remote aapacts, . ' a both aided approaah, sa authoritative a?preach and an adult role-taking approa h. TM results ahored that the last tvo approachee had no affect in . reduc g the rat* of takiog up saa1sciag. liia both-aided approach vea Pairly : effect ve with both unaa. Maphasia on taa Samediate effects of tmoiinZ vas: : effeet ve only ameog girls. The approacb that concentrated on taa loag term healt hasardvaa .ost effective with both groupa. to the extent of cutting ~. the r ef taking up amkiagia half ovar a aingle school year.. ' . 'L'here ave been savera: atteopts sinaa thaa to maasure the affuctivenasa oi aa an i-amokiag prograa aad more are ia 7r4Craaea tfost do not icvolvs relisau upoo a techniqve os another but attcmpt to osqoaa tiw studanta to aa much T00zo544 ~ . TIFL 0305457
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trointesti l bleeding was completely misaed in 6 patients.4 necrss. Of 85 cases of liver ab- IavEZn eee, 53 ere uoauspected during life and st disco ered at autopsy.' BRONC OOBNIO CARCINOMA. Metastatic lesiona, 'rularly thoae affecting bronchi, may prod ce clinical and histologic findings which au gest a diagnosis of primary bron- chogenic arcinoma. Positive differentia- tion may not be possible without autopsy. Primary ronchogenic carcinoma may ap- pear evid nt clinically and be confirmed by roentgeno am and by supraclavicular lymph no e biopsy, only to be discovered at autops to be secondary to carcinoma of some oth organ, such as the pancreas.' In the p eas, disease may flourish before any sym tome appear or before any changes i roentgenogram isotope studies or chemi 1 analyses become evident. When se ndary lesions from such a hidden site app in the lung, they often are diag• nosed as p ' y. Svs'LnL c AoRTzTla A review of 13,082 autopsies ormed at Kings County Hos- pital Cen in Brooklyn, New York, be- tween 195 and 1960, revealed 100 cases of syphilitic ortitis in which only 17 had been correctly iagnosed ante mortetn.* SARCOi s. A review of 6,708 consec- utive auto sies in Malmo, Sweden, showed histologic dence of disseminated aarcoid- oeis in 43 cases (0.ti4 per cent) of which only 3 had been clinically recognized before death.' RExeL NrAECTrox. Autopey data sug- gest that e vast majority of renal infaro- tionsare ecognized.' CrRaso Is oa Tna uvrae. Hallen and Nordenu int out that cirrhosis of the liver may cause few if any symptoms, especially in elderly patients with other major dis- eases. It ' ACtrrs tis ie &e manifesti nary dia pleural e atypically rs 4 shock. shown it ~ nodular .:I.- ' guiahable MsocAR ' I ' patbulogi ften is detected only at autopsy. CREATlTt9. Acute pancreati- ently misdiagnosed, cliaically itself aa some type of pulmo- , pneumonig, pleurisy, or n. It may manifest itself acute renal failure, ascites, or cent autopsy studies have masquerade ae subcutaneous .t neerosia, clinically indistin- ary.t6em. aodcwm-•, iT18. Ricetitetlir' claims that have stood alone in streasing the importance of myocarditie as a disease entity. He cites Saphir who found that myocarditis was present in 4 per cent of i 6,000 autopsy cases." In another series of 625 autopsies, it was found that in 9 pet cent of the cases there were in8ammatory changes in the myocardium. "In these pa. tienta, myocarditis was rarely diagnosed before death and in most of them it was not eveneuspected."1t BACTERIAL ENDOCARDtT1S. In a report *9h f th Phil d hi l G l H rom a e e a enera p ospital of 96 patients with bacterial endocarditis who -4 died and came to autopsy, the diagnosis of bacterial endocarditis was "more often missed than made."" OVER-ALL DISCREPANCSES. In a recent report from France it was demonstrated that in 1,OOO autopsied cases, antemortem diagnosis was accurate only 55.4 per cent of the time. In 23.5 per cent of the cases, there were serious ancillary pathologic con- ditions which had not been diagnosed clinically.l4 Other findings These are but a few of the many docu- mented discrepancies. What other discrepancies might there be in the 70 per cent of deaths in the United States which are not examined by autopsy? What is the incidence of antemortem velsus postmortem discrepancies in hospitals with low autopsy rates? The department of pathology at one hos- pital was interested in an increase in their autopsy rate for their teaching program. A survey showed that the autopsy rate was maintained largely by a few physicians whose percentage of autopsies was between 70 and 90 per cent. A program to stimu- late interest in the autopsy, however, in- creased markedly the general percentage of the hospital and the number of participat- ing physicians. The department of pa- thology held "organ recitals" once a week late in the afternoon, when physicians were more likely to be free, for a review of au- topsy findings. Cases of interest were pre- sented from time to time at monthly con• ferencea, and the pathologists diecuseed autopsy casesat a monthly review of deaths before the medical board. In thia way the staff was made aware of any antemortem versus postmortem diecreparfdes." Ze92 New Yr}rk 3tete Joumal of Medidne / Augusil, t%7 TIFL 0305426 + 1 111016 Case I te band night 'Phe c ~ce p ,cam l'-m c pronc who : unary his w had a drink, fonne had f little cLuse a,ked portec in the He wa a fsw of ste: Co histo. natio migh bask, shou: ~pous taugt• The that. cyan that eatin cand: the I: Mamt omy saved Hee nj~y With topam
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CIGARET'TE SMOKING A.VD DOGSL-HANNOND ET Ab F N lb d i H , esu n groupa . ogs °rou died the remaining L, d H would be tilled Kllling was rnnduct- ed' stratified random order, stratifiatfon be- Morfality.-Twemy~ight dogs, including ing •ch that the dop of each of the thxe hnlf of the gtoup H dogs died by day S.iB. grau were kePt alive fnr npprasimatdY the A1l remaining F. I4 and H dogs wex Idlled, length ol time. Until killed, eaeh r.main- beginning day S76 and ending day 899. ' di fdttip cigarettes a og smoked nneer Gtou N dogs were killed on days 9Q1 p each L dog, [our nonfilter rigaretts. a day; through 906 d seh H do;, nin. nonfilter dgaxttee a aY eri th t lity h e mor a exp ence ows Tahle I s p\ doga wrx killed atter all F, L, and H~ h the smokin d d T th d ~ g ay w en oga a m a a y , ing doga had been ki14d. :opsy waa perfoemed and the lungs re• were divided into four groups. through day as soon as poesible after death, The SiS. None of the eight group N dogs died; wex inffated by instillation of gravity-fed deaths occurred in two of the 12 group F td.hyde solution (fonsulin) into the tra- dogs, two of the 12 group L doga. 12 or half after which tfnie v.as allowed for ade- of the 24 group H dogs, atxl 12, almOst a firation of tissue. Dogs' L.ngs have s.ven third, Of the 38 group h dogs. The death four on the right side (ie. apical, csrdiac, rates of the five groups of dogs parnllekd the ediate. and diaphragmatic) and tftxe on the eft side (ie, apical, tardiac, and diaphxg- mati ). One specimen of tissue was cut rautise. ly t om a specified Iocation in the superior po on of each of the seven lobs, artanding in rd from the pleux about 2®. The specl- men was always takea from the specified loea- tion regardless of the praenca nr abeence of ap rent abnormality at that loxdon. A micro- e se<tlon measuring approumately 2 x 2 as prepared from each specimeA. agether, tbex wen 490 microseopta see- seven from each of the "0 dogs that died re killed (including the two dogs that died e day 57). The 490 stides weee randomized mputer-generated random numbeta and, in this otder, labeled with mmantive bes. Thus, when the aestions were e=gm- microscopicall,v, the xeder (0. A.) had no to the identity of the dog from which a on was derfved e degeee of ueh of tha follawing faotnx estfmated: (1) llbtesia, (2) emphpama turing or desteucdon of alveolar septa). ad-illre attachmenb to alveofar septa, (4) w, of aal)s of arteriole, and (5) ehfek- at the plevea A grading system .ea used rd the degrei of aach type of histologic ln eaeL inahncs, "grade 0" meeat "no go or normah' For esemple, Hbreeis was ified in grades 0 thxugh & Grade 0 5btsis t no iadieation of fiMoais and gtade 1, a rltght degree ae abao.is. Emphysema was claaFifatd in four grades, 0 thxugh & Normally theafls of arferinles ara thin and the pleux 1a fair y thia Grades above "0" lndiote ppter '•narmal" thickness of these eteuctures. e 0 for pad-like attachmenta to alveolar m.ant ttmt no such attachmente wex dosage of tar and nicotine relative to tnean body weight at the start of the experiment. Table 2 shaws the principal cmvn of death for each dog that died, the day of death, and the number of cigatattee smoired. Hereafter each dog will be identified by group and day ot death. For e.rnple, dog H287 meang the dog of group H that died on day 287. Table 3 summarizes principal raltxe of death as aseertained at autopsy for each group of do&a. Some dogs apparently died of a combination of causes. At autopey. all had microscopie evidenoe of prlettmonia at least to a slight degree, but no bacteria were found in the exudate. For Table 3, each dog was classffled accordmg to what appeared to be the most sevem morphologic manifettat;ee of diseese. In several inatattas, the degree of morphologic damage found at autopsy ep- peared ituwtfic]ent to account for the dog's death. Two de.aths (HE17 and H563) were due principally to pulmonary fibtutis and em- physema, and eight to cor ptdmotde. All ten of these deathg oemuted in doga ot gtoupe H and h, the Btst after 517 days of smok'atg. In dogs (lying of ca' pulmoerele, great :nlasgr ment of the right gtrigl and ventrilatlar por- tiom of the heatt was mar, promment than the degtee of pulmonary fibtcsa and emphy- aetna. Nine of the 28 deaths wete due to pulmo- nary infatetion. A thrtunblts was found in the right auritular appendage of most of these dogs; several also had a thrombus in the left atuiculer appendage. fJne b.d a thtombua in AreA Enuiren Health-Vnf ?l. Dee 1970 Table 2- 281 1.5 2" 1.5 3< 1.0: 320 2.1! ~16 2.3+ abi 2.3. .517 3.0. 563 1.u 60a 3.)5 625 3.9: 6<9 a." )16 4.66 753 S.U: l60 f.OE ez 6.11 767 S,Ic )9M1 5.<0 the vena othervein Four c H287) we monis. In and, in a - uted to d, vanoed pu emte empi At auto the larym the Iaryn: The lungs of these dt cigarette c T 00;;0q3g TIFL 0305396
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-7- llle JC u.e3d is 12S,,c and C:76ueZ,~inS--in reSea-rca, in greventio.^., 81'•d in p%~z1te i.Z_olaaLion cn8 cduention. ',te must wr:e harder net orly to prese:vo the Geins we .ave au•ce but to cia<a he.:dz•r.;y a;aSnst the continuing tides of pubLic :nertia and nivate self-interest. t•:orking together, I am confident we ori_L1 f ~lrv f:.U. TIFL 0305475
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pbo3 ~ . :his pro lea of exemplara and the aduit :rolo ic cc=,~ded for ,eae::ora. pa hava,fou ht a long battle in this country to ya:n personal freedoa :or tesaSa:a. :he righ to be seen at a party where liquor vao :a.1ad. The rigot :a d:aoa casually around his home aad on weekanda. :ae rigat to smoke. Taia v.:s ao.ad_ !.a a ree rrah moeoraodm Lram the Ndtional Sducation Aaeo<istioa in D.uo3Soa, ~1960, vh h was concaroed with school .-.a:aa,q policies. Scbool ai~i:aa :a:or0 are, I t ink, reluctant to discusa t:ia probiea with teacuera eo: fa« o: appaar to be iaterfering, with paraoaal froodom. Koreover,'if the ~aol adminiat tor emokes, it beeomea douSly di:ficuit for bim. Out will t:w . problem 80 away if ve ignore it? The Natio ago repo permitts districts RcVorter oEtheec 1 Education Association Reaaarc5 :eror:adum mentioned az:a-,xnt ted that wlile onLy 13.6 percent of tSe urban school diatricts quoried , any student smoking in or near ac4ool buildinge, 66.3 perceat oY the had facilities for faculty ew:dry;. Tne ELucationaL Reoea:ch Serviea in April took up the problm ae.:in. at that tiari, only 7.3 percoat. hoola baoned saoking by tecaSera " t1w achool grounds or ia t3e =- teacbers ia o:a district had an aali.-;S:aair,Z ' buildinga. A mamorandum sent to . raco®endationa I iacourage smoking by faculty ce..bers in 'open' areas. 5. ( uotation t+arka were in tye original.) (Scaking should be one only Ya Ieloaed' areas cuch as the .`zculty lounge.) ` io ia necesaary if the ataff is :o sat a good exsmpla in a rograa to discourage smokiag aoon3 out youth." ; This aa to strike a rather anoaaloua poatcra.. W::SIa reeognising tha'e::eapl« rote, we ke prwisioaa to saoka, but ean't 1e: the kids faculty tateb,ua.:k Aa•if they do r.otraco„»i^•a'Che c:4uda to13.iIZ out o: t5a . oom. .. ,, %tQ0Z054£, . TIFL 0305461
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page 3 • uhy do th4y .tart? Several aseociatioas are conaiotently found in the studies conducted smok• the if hia or lower goa questions do not be smokers, who smoke non-smoki up of smo component so far2 1) the child is much more likely to smoke iE his parents . if they do not emoka: 2) the child is much more likely to amka her friende emeke; 3) smokin.- is aore eoooon among children who have s, lese ability and achieve laaa. Thaae findiags raise u many as they answer. For example the children of some smoking paraata we snokera--uhy? Conversely eoma children of non-eookera become hy? Does the nmoking boy or girl tend to associate with people or do his smoking associates cauea hia to start? What about the g studant?-Wny doesn't he :iod it necesaary to smoke? The taking ing undoubtedly baa its cultucal, its social, and its personal , bleodad together in a fairly unique composite for each child. We could ontinue to ask and attempt to answer questions such ae these, gut , the quese a before us ia how to eope with t:u probiam. Considering what we presently know about starting smoking, w3at can we do about it in the scheolal.` A great d al is going on in schools aa va all kaow. Very few attempts aL -• avalustio have been made. Currently 44 states oava either developed materiala ~~. apecific ly for use by teachers, or they plan to do so. These materials potentiy y reach ]4yj percent of our seboel-age children. yilsa, postars* exhibits, pasphlets,.books and speakers are alaast universally available to •4 earey t message to the studeqts. What mesaage? What do ve tell thea? Do we te7LI thes that smoking..ia dirty or expensive, or that it stains the .fiogara,latuots the growth and tuts the viad? Do we teil theo that smosing causea_c4 lncar ind respiratory diseases wd iaassociated_wttn sn iaeraase T OQ20543 '; TIFL 0305456
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LIBFL~Y The Tabacco InstitIte, Inc• iGAR~.iTt: LABELING ~,dD ADYERTISMG HEARINGS .. ~ T= COAMITTEE ON COMRCE IINIT.ED STATES SENATE EIGHTY-~YTH COil'CIiESS -BTBST 9E59I0?7 . ,.,. ~ .. . : ._. S. 559 and S. 547 SII.IS TO RECIIL3TE IdHELING OF CIGAREITES AND FOR OTHER PURPOSES - PABT I . ]tA808$25,2i2R.^J',3D,OpBII.idL'DT,SDQS - Prinbd tn W ~ u! tII. Commiw. an Commaae as eovsn,mnyre rnr.ixr.rG Oar=ca ' aAsstrGTOV : nea Fa a40~ti. Yprpb.y.enf Do.oswb. U.B.OS.eevmst lelntlq Oms wrWe~mb D.C~9w: h1miSOD 70020555 PA - 000483 TIFL 0305467
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- 2 - efCorts'at Suba rCiag Anti-SaoSaing Activities. These efforts surfaced ia tr.ahington last month during heasings on cigarette advertising z-:d 1abe11ng. Testina , as you know, was supposed to deal with health warni:.3s, aut S-ioking and He Ffe heard The evid can't ?rove a: And this: hest disesse. Also thi ,.ion2 And this: cealth. You map changed their ei look at the wh As for he the arguweats They'=e t::e health dsnge decisions. Also this you can't tell h-zs spent in challenging the scientific velidity of the th Report. ' such things as this: nce of the ha.-zf*,Sness of cigarettes is statistical--and you hix6- by statistics. Ci=arette smoScing has not been proved to be a direct cause of Therefore, rare research is needed. . Don't blame lung cancer on cigarettes. What about air poLu- Xedical opinion is divided on the relationship of saoking and t have heard this one: tFembers of the Advisory Cocaittee have s about the Report, so r,+a;rbe you had better take another thing. th warnings on cigarette pacicages and in cigarette advertising inat tcm run like this:. scessary. A-erica-.s have a11 the information they need about s of cigarettes aad they can be trusted to make their own or.e: - Once the gover-rmient' starts enforcing warnings on cigarettes, ere t.J will stop. Maybe i:ax-,ings; on alcoholic beverages or ea ax9oTWSiass 5+~il 'vs ro"t. 6!ay pio:c a~ ciaa:e`-~ss? 0555 -t- p02 TIFL 0305470
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of the clini ' n. Meaningftll mortality and morbidity a tistica can be assembled only by analysis of postmortem observations, not by gue work, no matter how educated the guesser. Conclusion I have p posely conHned my remarks to the diagnost c aspects of the autopsy and to the role of , e practicing physician. This is not to sa that I am unaware of the im- portance of' dynamic pathology" in educa- tion and for naic medicine. Nor am I un- aware of th psychological, legal, and prac- tical diHicul 'ee inherent in any attempt to increase the autopey rate in this country. The improv ment of medical statistics and the ultimat improvement of diagnostics is of su9'rcien importance in medicine to warrant an onest, thorough evaluation of the autopsy nd our attitudes toward it. We stand today at an awkward, uncom- fortable po t in medical development. We are bet een the age of diagnosis by as- sumption, h ry, and simple tests, and the age in whic the computer and more elabo- rate diagnos ic technics and services will re- move the work from diagnostics and narrcw the ap between antemortem and m dia postmorte gnoete. Amr !N 19' udde "ear ( not n baugh pulmc They TT violc uter. patis cbill and• to sh and The consid waa ti vesseL squaa alone. They eaper: cond:' Senior citizens in New York State References 1. PrDkiot.J.: addmdacnWe:Dbo(ead.>'..urnp.y~ J.A.M.A.1e4r 12YI (Dee-1J) 196a. 2. HendsuoD, R R_- Pulmunary embclim Dd iDfare- tim, M. CUD. North Am.in 48: 1425 (196Q. 3. Hodtw, C. H., ond Good, C. A.: Pubncn.ry emboWm and In4eetbn, ie/!. 48: 9" (1964). 4. aerkowits D.: Patal tatrdnt~Nml b.me:hap; d'uavoae implinUue. eum a rrudr of 200 oen. Am. J. Ga.tramteeL 4e: 372 (196.9). 6. D{deD, W. W., Hmue. P. R_.nJ Rl.a J. n.: U.w sE.u., PMP.d. M.d. ae: 11 (19et). 6. TriNdad, S., LN., J. R., tuL Ro.onelaet M. a.: a,mcAapnfv u.+imm..im.ilatd by meuaatie Wma,e, C.w.r it, 1e21 (196a). 7. Hertv.K, H. A.: Sypbi6tlc anrUt4 A duveo- catkdoric euu,rr,rudy of too aw, 1s30 tc 19001 c1,cela. em f9: ale n9eq. a rnael. H. LL ee,ouiLeai, Pu>ter.d. NaG. ]a: 496 ass+>. 9. Pml.nd, M., aDdd Pvamm, T. N.: ReDel arpacb of uNlac diw.r, M. CIiD. North Amerlp Sai 266 IJen.) I98a 10. 1YLLa, J., and NcNa, J.: Livo drtbo.o uw,u. prxM durint 116% A r.eis ad 79 ur, J. Chnaio Dd 17: 961 (1994). 11. arLr»r, R. W., and M.Imoq %. L aubcub,wu. neduW GR Dwxo.ie in p.mestltie, Arah. rnt Med. 110, Bsa (r1.o.) 1905. 12. RImWll, M. L.: ttywrdia di.nw in [ha a{ea, Ine7mUet a•e.•ie. ef ehe libnw.. J. M. c.ri.<ne 8ee. 1Gt 4 IApr. n 1904. la Cnayv, &. S.. cwpr, J. W., .ud 9cpneYl, T. c., Jr.: Pitrilla in We dugcaia n[ Lavlerfd enday.dita A r.vww er 169 P~b wae ®phaw m 96 wiW autopey, An3 LR Ntl. ltat 55 (July) 196a 14. Hb.ecan ]., C8n9ue, J., Jr., odDdarien, P.: AD- pniW or oDe ~ nwot .naemeeliWe.t conhmn. tlcu, Bdl. Aod. oat med.14T: iiel (196a). 3a. Do.Wt9 HoWtt.l, N.w Yoek, N.. Yuxe: Dnpub. 14eee dae4 196e-186T. 16. Cr..WekD., N.; penen.l ^^•••-s•^+rtiDD. ADN, lse.c group ie expected to increase steadily, reaching I nearly 3 mihion by the year 2000. lli{lllAmong State Health Depsrtenent progrnms, coa of particular help to older persons involves screening clinies for varioua chronic diseases. f I.ongevity, the ultimate reward of good Some 12,000 people were given a total of 50,000 health, is on. the upswing in New York Stat., tests l.st yeer at multiple disease screening according W State of New York Department cliniu in 18 communittea ' of He.lth. o afate in the nation has more Majes chronic dieeeeee that aHect the alderl Illly residents in e Mediearevge bracket, sisty-five uu:lude arthritis, heart trouble, diabetes, cancer, , and older, New York. Membership in the stroke, and vision imp.irment, Studies bav 'e elite cent club hae quadrupled in one shown that in the popu4tion as a whole, 46 deeade, In e most reeant estimate, more than per wnt of the people have at iesa6 oae of these 1,000 New Y rk State residente are one hundred conditiolta In the aizty-five-and-older group, years old or older- Even motherhood is en- thi.perceotageriseeto88s loyed by aa lder-sge sroup: Esch year, same Incidenta W, although New York State has 360 babiee ar born in the Stats to women forty- the largest block of elderly citizsns, it ie by no flve to fiRy, Oae or two bitthe a year are te- meeas ac "old Stats." A.aording to 1966 portod lu w h the met6er's ape en si.w as cawn Laarw, New Yvrk'e saY1y-Lvr.ad-elds : ovar 5fty, rdSng to the latest figures, New group comprises 10.2 per cent of tpe total York State 1,886,000 resWenTL aged sisty- populstion. Seventew other etatea heva higher 6" or older. The number of people in this age percentages. 2084 New Yor State Journal of Medicine / August 1, 1967 TIFL 0305428 huma. the m fluid. nism, shock They rence obete In amnic tient from tiseum report that '. esp'ue •Pw KbOas 4
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I Emer ing Anti-S.9aking Activities of the Federal Govermeeny" by Luther L. ~ ;d. D. Surgeon General, ?iolic Health Service U. S. Departaent of Health, °ducation, and Nelfa-e Shortly after the Report on Sa:osing snd F:ealth was released, one of the first to take ssue with it w-s that a.cster of light verse, Go^den Nash. In a poec which app ared.in the Saturday ?ver.±^c 2cst in March, 1964, he aade it quite clear t he ic not a slave to tobacco, but added: "It's just t:-iat _ cm a cross between a and a mzvericCt, "I woa't allow -.,r life to be regulated by reports whether rct'-1y opti.istic or gloomily CaGtJC:iC." . ;ae ti`IC of t4ae verse, inci:.ent2.l.Ly, was "The iCinsey Renort Didn't Sipset :ie, Eit: r." . . ti Of colR'•e, a'. ..~.. :P:u Zom P:.d is ::.t Jlone in his view. There are o:i;ers w'ao hav yet to 13e eon•r.nocd of the •raiidity of the Advisory Cocaittee's Reoort on the ealth »azards of ciHz,.rette =olcing. There are the sincere disbelievers - and what naw 'snowled; e has -ot broumhtt in its wake a minority of . s;:apti6s? And there exe others 6rimo seeic to discredit the scientific evidence. aad foster the illusion that cigarette c:o:aiag is not injurious to health. As part of this afternoon's toyic -"-.:Ter3ing Anti.Ssoking Activities of tha Federai Governmant" - I orould a.ie ao talk briefly about reaent *'~a;ion.STube cLlosis Aasociation ;.:.:.ur1 :•:eecin.~,, Chieago, T1i., TL9% 31, 1yo'j •-T 00::055'7 - PA - 000484
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s_ -3- s: Yobod}r will pay attention to health warnL-gs aay.vey. by no aeans exhausted the list of arguments and I don't think we our tice here answering all of them. Most are broRen-recard ave heard since the day the Report appeared. Many are repetitious nnipuLated in a conti::-ing p:roZrem to shake public confidence __y e iatended,.as. i reccaa arti._r in Science N&g2Sine has said, e '-ression."thatt there- is- no nore evidence against tobacco thaa - st~t~a.ton;so• "" . ..c:, ,xP..._- . . . ._3 a ence needs no brie:ir.g on the evidence or how it was arrived =o:r the history of the Re7ort, for 'r:ie National 1liberculosis Association paY of it. •_v w too, that the Repora con:Yr-_e:: ':3e evide:ee a."ter a massive study __ And'I r.ay add that none of taa Wsoers o: ~;::a Co-ittee has •- nd on the findings. Come to think of it, there has been a change. % had been a cigarette =mker until the Report was issued, has given ^,f the nost persistent ploy of the dissenters is the charge that 1 s stat.stiea.l and therefore inconclusive. Icsow, the statistical relationships involved in the Report . -'•d ed that smoking is a liice]y suspect and led to further investiga- ', experiaents, and clinical, autopsy, and population studies. These es of e+idence resulted in the indictment o£ cigarettes as a hazard. *00Z05Sg TIFL 0305471
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7f$1 CIGARETTE S.ISOKl.VG AND DOGS-AUERBACH ET AL n we smoked by other smoking dogsl. We ude that the smoking of a large number of on8lter cigerettea daily for over twu y iyll lead to the development of inva- siv bronfiioluwllvcular tunlula in Iltale taa- gle ogs. of the remaining dogx that smoked fll -tiy cigarettes and thaae that smoked ta ae many nonNlter cigarettes were killed aft 875 days of smoking. We have no way of ing whether any of these doga woutd hav developed invasive tumois eventually had they not been killed. B uamow cell bioncAia) carcinomas of mi pie si2e were found in two doga that amo ed many nonfdter <igarettes a day and we killed after 875 days of stmkiltg. Such mrl ts were not found in any of the other do We condude that tnale beagle dogs are suitable erperimental animais and that mu procedtues are satisfactory (or testing the nilative potency of various typea of ciga- rettea in respect to the pmdist/an of sqtia- mous <ell bronchial arcinoina, provided that a large number of animals is employed and that the dogs smoke for several yesis. '17,b ftudy "~ mpWried in pert by a tea.enb tswt 4<m rhe Anwlina Onco Soeiety. Ine 2ha fnttowiag phyiaiem tevi.wed minmrepie 9idw from .aar- in .11 c/ th. tmnear ,Iolu 61. Brle. \iD. heed Epidemininrit P.Ihota;y Uait \.doop C.x.r Iwiaw, l:atioeal )astih.an of Haalta, Beihe.dq Wdt B.uM Gne, MD. chi.t. L.bmaop Servfc., Ven.an. Admieiabeiiee, P.Io Allo, Cal1t: Sv.nd lY. Nie4.n. OVJL Drp.rlmeel of Anlovt Diuoro, Ueireoity of Conneettcut Staea. Ccu; ShiNd. Wen+4 MD. Nw Englud Dneona4 Ho.pitd. Bmmx +ad R.Ymand Yu- oer, MD. CMd of 5mg and C6iM LaboMory S..- vin. Veynn Adminisnadea Haepiml, Wrs Hav. en, Cona. 1- J. W.lYr P~And .tl .hotaanMlia m.bri.l tor IL'a etudy. . Iiefaex.. 1. d EC, Auw-0.cb 0, Kimra D, et .1: Eg of cipntte amoklag oa dop: L Dniga of az oiottatlty. and Budleoq 'vo lual w~ c6 Arch Ena(m Hentth 21:,'10.7:a7, I9i0. 2. ebow AA: H.enehielwlv.al.e eueinem.a A rn lntern .Ned 16:179.7l6, 19dn. 3. R Jll', SchultelWld D, Hutter RVP. .t al: Hia bry. Epidnnlalory, and End Rnuffr. The Ilem ' Ho.piml Cnaao Rea'vlry. Nw York, M.m ri N Hoepi4l tor CwM.v ud ABied Dis..ae; 1989. [4. .mmead ER Hom D: Smeeiog .nd derdl n Report on ai mwrlu of faile.-uP of 187,7e3 m.o: IT. Deat6 at.e by nur JAMA Ia6:l2G- 33oa. r9se. S si W, Ionland Dq Siefm MD: Llmg moAali/y a. nletsd tu resid.xs ud amoW ing tetlee: L IVhlt. :Wea J Nat Caneer, fnat la:9e .Inel. 196t. 6. d IC: Smeklee in nletiae to d.oM nir 1 mlBiee mri end wanrs Not Caneer !na bf p IB:L29-te{, 19e6. 7, tdD, ABu WH: BlvaOtoloeiwcler tn. IDeo et tae hag. gaB HopRur XaP 1a211b133. 19113. & CF. Rmdt.es KP, C.wnar. Iil: Sroa. oDb fe1v.W.r MI) eueesme o1 tM luy. J T Sarg2esv41uR WeJ. A y 2C s6urise JtS Gw WE: Hno- 1%R I0.!.e) . lalvwler wID tumwt Arca Peth $P:3556, pexwH, ReYqaC PVhaaury (bnnrhio- Imta J Pefh Beer 71:1I6151, lAi6. 1L C.mpoaum 0:'DIe cbu.Rni.tin ai p.eipl. xd luryr Wspn that wtiAt dwr bnnehid.o..lvr ler ante. Bnr J Canal YAe56w4 IeeA 12 Aueeh.cb 0, Staut AP. Hemmoed EC .1 .1: Caang.w in bnovhial sptdMWm In nlelioe m Cir.- rotto .moking and luag eanew. Yw Ena J bfod 16114253-467, 196L L7. Niala.n SW. He.... A: Prim.q Wlmee.q tumon of the dor: A nport of 16 nwa ! Amv Vet Rs 33813$'„e. ]9te. . 14. Ni.4m SW: Cempoeeli.. pNholagy of pul- meeery dia.w, ie Lieba.. AA l.dl: The Lure,- npnegnpe 6. Intemuioeal Aa.d.my c1 Pataolegy meaaavpha, Baitimmq IVillie® i Wilk4n Cq 1987, pp 2M-tN. 1S. Btodey B8, Cnie PH: Pr+mry putmonary . asoplurro in th. dor A nview al 29 oa.. J Amer ye1lled Arree i{7:16n3~1613, 1966. 11 Jubb KV7, K.nn.dy PC: Panbtory or De- merar Aninr4. Nw York Andemir PAe lae, 1967, oel 1. 17. blanlue W9: PrinsQ Petmmery nepta.,w ie dcmeftio eninln4 Seumspt Var 6t131-1.U, 1964. I& HaR.y EB, gPeer FR 7hompeen BA, a•I: £qp.im.eW endy oe .deet or riprotfa smnl4' cundatoob m brendd.l mtsar. JANA 1a716et- ]090.19at. IA Clarke WJ, Prk Ji, PeloEq JL at al: Ptutonium ialldetiea .mdiw: VIL B:vadrida+l- vwier nlaime of the o.eme Iwtr fdle.ie( plu- tandtml pardrle ioh.LYae. Hwtd PAye IeboP6u, 196H Toozoa"2 A-A 6..w:ron Fle>/tA-Vnf 31. U.e 1979 TIFL 0305419 Lo Gu Ycvs. Krnry 7nnt 0.13, 1. nary lu+ umq n- cemWer bon nqn c/langr. He:nelok won na riral w- .4mhla' the ypuF denot an many pr,, 57 waeb: Ieraaled i 5.72 ppm Crepe In . penlyd by S VLFC7I . . of ilrban a the s®atti, in antnfatet diwted tu 1Dlnfeey ' Submilttl •retl y Fpmi/y} sCe4a Gnh rt Ihe Dei.e b•. M4Fed., vfw. Ont.eim Repr'vlt :pl. t9Boz]B.F: ii-
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%." paaa 9 . IIy providi diacuae th smoking. ?craonal 1 problems f call a fac :hio shoul to hia rol cmoking be about the about amok g the teachers with a hir.covt `z ct.ici to c,:ce cad :ail_r~ -.o problaa, we may be crcati:Z :a cyri:n:-aat :aroraS1e `.o ciz;.::eta ow that fraewa froo cr~:aic::aavo ca::ol of tha tcachcr1a fa La a faL-1y accura .c..c. ia a c,at tr: a to ciccuca cwa of :ka " an&ly and openlyl : vau:c: pza?o:e t:_t t::a ocaaol aL»'ai: :c:Cca .. 1cy eeeting co di:eu¢a, ....-.:ay, t:,o ...a:.yl.:: :ola of :ha Zoccaa:. be doae not to'prea.ure c^.ycao into oto?pL^.g but to o?ea hic aL'd aod to gat hiai or her to roaiize Gtia vGrea to dnich 5a o_ haz - avior affacta hia ovs attitudaa tad the effactivena:a oF S:z tc:.chi:g ffecta of iaiOkiap°. Cqa ihe J:an^o teac::ar i:.aor7orata L:8 -rvlledoa Ag aad health into hia or baa a`.:.aa rocn dincus:ioaa ct s.aoly cs the non-e kiag taacharT IIy the s"a to::^•n, c.:r. the aWokiag aLaiaia.:ccar encourage e davele;=aat of a noa•c-o:S:Q = iaeu co readily ,:athe taa-«aadminiatr or2 The creation of a"aoa-wo:ciag." milieu ia of vital `saascs. It is the rich coil Sa'.o which we caut t::a caeda of idea groeth cad davelopmaat. It need no eonauae valuable curcieulum time. S+Caaa the ::athe_Ciea taaahea discusses rapie cauld ha use lung c^..:.:er deatb rateol Could the ZZ;~raS teacher cuaa a8vertisiay eopy= Xi;,ht t:.a C:vica or ni:tary taacSa: di.aca:aa : - the role f Coagreas ead the Faderal Trada Co;=iaaioa in davalopi.^y ecnci:.a: :_ '. , eafagw aad the s::aota or Saduc:.~j :abSia:.T In ahort, we naed to Sacome coaacioua o: =kiao =d ouz attitudaa ccwLdo it. We ad to t9iaags the atmoaphere 2:w oao ia which ..Woi1a„ L: _ accaptabl to one ia viich it ia sot ca a:ocopt:.31a :orm o: baSav:or. Z_.:a teaehera tisg.tada?eadently, is an oaar.tial caa?onent ia thi:. attc...~t ta ?-005'0.710 .TIFL 0305462
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Surgeo General's Report The Sur;eon Ceneral s Report on Smoking and Health' and .he vigorous educat onal program against risk factors !iy the American Heart ssociation coincided with the on- set of the change in ortality trend. This encouraging fact should lead to redo bled efforts to prevent atheroscle- rosis, However, the rep rted gains are small; the magni- tude of the problem i vast. To meet the challenge in- telligently, we must kn w the trend in 1973 for immediate feedback to assess and odify ongoing programs. Could a corporation survive tha has not yet completed its 1969 an- nual report? : Its operati g executives would learn of plans to deal with the NIiddl East oil crisis in 19T8! Dr. Ingelfinger, in a recent editorial in the New En- gland Journal of tMe icine," has pointed out the in- congruity of Washingt n spending $80 billion yearly fcr health care, yet hesit ting to allocate 1/4,000 of that amount to the National Center for Health Statistics to ob tain facts that would h p decide whether this huge sum is being spent appropriately. It is time for :he American 3ledical Association, the American Heart Association, the American College of Cardiology, the National Heart Insti- tute, and the Congress of the United States to demand more timely, factual information, and for :nedical spokes- men to utiliae it more meaningfully and accurately. WELpONJ, WALKEa..'ID Editorial Board, JAMA l. W aqner HN, Stnu® H1Y: A New Apqcadt to Cmnnan' Heart bis. ease. Circ,dction ta22Y"31, lBiB. 2. Cordav E, Sman HJC (zds):.NVarardia! MfereHo. New Per+rlires in Diaynwie ond.traxayrmen(. aaltimare, Williams &\Gilkine Co. l9'i3. 9. Smtistim! BefteHx VetrApdiln. Li/r In..rann ioapan N. 54:11 I Feb. ruarr) 1973. l S4uRiag aed Health: Report q'the Adeixa.y Cummitrrr to the Surqene Geaera/ q'the Pohlie HeeIM d.mra. US Dept of Health, Edmvuon, and w.ifan, 1964. 5. Ingelfinger F7: Nationat Gntsr for Health Sladstirs..v E•p J dfoi 284114&1143. 1979. I 1 U C CRITIQUE &CAVIL . e e This commentary f lows up etn an earlier promise to discuss unusual c ndltions tnat cause coughs and thal coughs cause. You may recall that a report of a hair impinging on e ear drum and causing cough (JAMA 223:1269, S 73) led me into the cough chron- icle. But before I d ve into specifics, perhaps I should snare with you suc vital data from my fllesas the tact that the air stream eloeity of an American cough is about Mach 1 or t speed of sound (750 mph at sea level) (Can Med Ass o J 75:524, 1956), whereas the air velocity of a British ough is about 200 mph (Br Med J 2:223, 1960). This Ispartty in cough air velocities is somewhat disconc rting; perhaps it reflects on the one hand an Ameri an tendency to be explosive, and on the other hand, a British tendency to be discreet. Another item of i telligenca from the files is the ob• servation that a co gh sprays partlcles about 12 to 15 feet from the ema ator at a speed of 160 feet/sec (JAMA, 158:565, 19 5, as cited in Am J Surg, February 1955). Don't yield t an impulse to equate lhis to mph or you may be non lussed as I was by difficulty in re- conciling the reaul with my, prevfousty cited data. And now, what are some of the unusual causes of cough that have been documented? It a hair on the ear drum can trigger cough, it shouldn't be surprising to see that excessive cerumen, a small foreign body, or eczema in the external auditory canal have been In- criminated as causing vigorous coughing. There Is the so-called psychogenic cough or cough tic (Clin Pedietr 8:560, 1989) and the elongated or edematous uvula is said to be an unlikely cause of cough. Uvulec- tomy is not recommended as appropriate therapy. One patient coughed spasmodically whenever he turned his head, this curious concatenation caused by a neurilemmoma of the vagus behind the lower portion of the sternocleidomastoid (Chest 60:355.. 1971). I have a report of paroxysmal cough induced by a trans- venous pacemaker (Am Heart J. 81:719, 1971). Finally, rhinolilh, cerebral neoplasm, parathyroid adenoma, and anomalous innominate artery (pressing on the trachea) have all been implicated as causes of cough. dEoneF x. Tpr.ae. MD CoraributNg Edtor b c r 1046 JAMA, MarOh 4J 1974 ' Vol 227, No 9 TIFL 0305434 Coronary Mortality-walker
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/^ b PA - 000488 23 '7 0020575 TIFL 0305487
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Aaa Geneic2e ptediae et Gemeltologiae ically simil r individuals. The present preliminary fiwra seem to support the xssumption hat tobacco consumption is associated with angina peccoris and chronic bronchitis, uhcrezs they do not pcrmit any conclusions regarding the other disorders and sympto s. The det 'led results t.ill be published later. Dr. 11. H.ccz. The [.'niverau. Imtitute e( S(uman Geoetio. 7ag~q t, Cnpeuhegen V, Dsavu>!c .; ~ 002U$:? 336 I. (Ayc, Terr: vore irSez orot di L dou tita me sok la po F: F TIFL 0305484
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A saconc t'%in co:c~_ises L11 tne ±nvastzqa: p:o^ine:: Brit :rot=ca1 fiedic s_ates =.`.et ao ase.'~. -cYt21i- t-,ny was basad or. tho Danish T;•rin Regir__, ,r.',ic: born `_ : Den,a_k bcte:een 2.870 and 1920. u:a cf rs conccc=iny this study was Dr. Donald D. Ze'_c, .; sh eaiCe^iologist of the Lonco.^. School of :'.vcie ne ar.'. ne. The praliair•ary =eport, ?ub1`s::ad. in 197J, e of the pairs o: tusins"sho'•re3 any ta.^.ce nc~, to incre- in tha hzavies s_o:.iag co-ttriIs". Preli-inary_cs~lts hat there aOpea_s to be no significant association a nd coronary occlusions, one c the co-=ocest causas ? ti ~til~ Lo-~ ti- also incicata " be.::een s,o:c:: o: ceaz:. PA .000486 TIFL 0305482
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-6- Intereg ncy Councils an S,ao'sing and Hea3th are operating in 29 states, -;ore than half of them having begun fo].louiag release of the Advisory Ca.aSttee Reaort. - The Se: te Cosseree Cocittea has approved health warnings on cigarette ?ack+es. The labeling requirement does not go as far as wa would li'.te, but it, s in the right d'rection. The Interagency Council plsyed an important role in the Congressio a1 hea.ri.ngs. -y A Yatic Clearinghouse or. Sxo'sing ar.d :'.ea1t:: is now operating in the c Health S rvice. The House has epproved a$2 million first year aapropriation to yerait this .it to serve as a central point of study, coordination, inforxation, -^.d liaison for prograas in this field. This, too, is the beginaing of real progress. The Rea rt an Smoking and Health has gone into a second printing, with more than 35C, copies already distributed. Five separate health inforas.tion pa.»:1etsderiv d fron the Report are bcing distributed by the tens of thousands. We are voived in a numbcr of studies on the behavioral and motivational aspects of the kin„ problen,'includi:.g st•es of adult and youth educational programs, wiffcI awal clinics, the role of ph- ysicians and other professional health wor:cers, and th value of grou.) tres.tment. A Public Sealth Se_-viea last fall showed a drop in the proportion of adult cigare te sWo:urs iroa 59 percent ia 1955 and 1962 to 52 per cent today. Expressed anoth r vay, a;;e decline of thmsa seven percente,e points, added to the 18 ter cent of ult r..an +_ready of:' cig_ eates three years ago, means t:at nearly one out fe•,:r o3•,St n en is smoker. Thus, s of ts enerLing activities have hsd a discarnible and eacoureging ef°act on the s_ Iaing preblemn. Others havo fr.iled. Reth the successes-and tne f.:ilares are he7J,ing us to loa:a hoirbest to m_at the problem. I T oo20ss2 •. TIFL 0305474
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--..:.:. CIGARETTE SNOKlNO AND DOCS-AUEItBACB ET AL 756 Inrastve :nly In H group H -ht n/ 14 -..;zded to quamous ,o Jt 12 ors and ; are re• -~.adurea che pn- 01 one dre pre- am each tu and !er the :imgof ...:cle dogs 'aring the smoke; n have a e eaperi- <moking zroup F :3 dogs) i2 dogs) half aa many the other dogs. Group b dogs wen hearier thsn the othen; we planned to uae them fo a long-tems experiment Twen j-eight dogs died between days 57 and g7n: 2 o group F. 2 of group L, 12 of group H. and 12 1 group h. The remaining group F, L, and H s, and all eight of the group N dogs wem kil ed starting on day 876. Auto woa performed as soon as poe.ible after do th. The lunp were removed ard in- Bated h gravity-fed intillation of fornmlde- hyde eo ution (formalin) into the tmchee. The lunga of beagle dogs heve sereo lobes, fnue on the righ aide and three on the left A epacrmen of pere r1ayme was escised from the superiee aspect a each lobe and prepared for histologic study. he remsiaing portions of• th. lungs ..are a rebed for masaee of any Idnd: such massee en prepared for hismlogic study. TAe tracb ronchial tree ..+a th.n disr<ctd out of the 1 and divided into 131 pordons, each of which embedded in paraffu A histologic section as prepared from each of the parat- gn blx from the upper main bronches and from th right and left apieLL lobe broochi These sections were se.rchd micrr.copiol• ly for h evhiol tumnea. (The other 109w01 be ssamin later.) All the semeining lung tiane uu em added in 40 or more paraffin blocls Sections from each of these blacks were exam- ined mi rwcopically for tumors \tany ssetione from a b tumor and its surrounding tissue were e, in.d microacopicalfy to determine histolo tyye, sin of origin, and extent of growth. Rentlte Tab] I shows the group (N, F, L, H, or . h), the day of death of each dog in which one or re pulmorrary tumere were found, the n r of ciganttee stmked, the. age of the d at tM titne of death, the typo of rumors the lontion in which the tmrtor knd was f . The day of death means the n of days from the first day of emok• ittg ''dual dogs are referred to by group and of death. Dogs which were ldlled aiter 613 (4ncfuding one dog which died eftc y 875) are identiRed further by the letter a or b. For example, H89?a idetti@es one list up H dog which was killed on day 592: FI 9?b identifiee another group H dog killed e same day. Tum rs were found in the lttngs of 36 dogs. majority of these, both noninva- sive an invasive, were in the apiml lobes with a predilection for the lefL Two tumors were early squamous cell bronchial carcino- mas and the others were bront4tioto•alveolar rvmors Twenty-four dogs with bronchiolo-alveo- lar tumors had noninvasive tumors only; seven, invasive tumors only; and five, both invasive and noninvasive tumors. The rela- tive prevelence of tumors in different groups of dogs mey be compared by disregarding presenre or absence of invasion. Table 2 shown the aumber of dogs artd the number of lobes in which one or more rumors were found. The prevalence of rumors was highest in group H dogs and lowest in group N dogs. The prevaleace was somewhat higher in group L tlwn in group F. Of the 24 group H dogs, five had no bronchiolo-alveotar tumorg; nine had a tu• tnor in only one lobe; aia, in each of two lobes; two, in eaeh of three lobes; and two had tumors in each of fotu labee. Of the 12 group F doge, eight had no brotuhioloal- veolar ttmton and four had a tumor only in one lobe. This di8ennee betwaep tpeup N and group F is statistiolly signifismrtt by the Wilcoxon rank stun test (P<0.01). 'Itte differences. between groups H and L and between groups L and F are not statisti- cally signifietnt. Nodavatii.e Broncbfoloalveoler Tltators. -Noninvasive tumors (Fig 1) wete found in the lungs of 29 doge. Since they were generally mufticentrrc, the number of truly independent tttmon is urtcertain. Howaver, in same dogs such tumun were found in two or three different lobes; one nuy asmtme that noninvaeive ttmtora found in differem lobes are independent Noninvasive tttmots were found in 41 of 203 lobes of the 29 dogs with sudt ttlmots .. invasive Bronohiolortlreofar 'htmon.- Invssive bronchiolowlveolar tutnors were found in only 12 dogs; all had antoked non• fUter agarettee heavily. The 12 dogs wen distributed as follows: two were among 12 grpup h dogs that died: twc, among 12 gteup H dogs that died; and eight, emong 12 group H dogs killed after day 875. Six dogs had invasive bropdtiolo-alveoler tttmom in only one Iobe: faur, in two lobee; and two, in three lobes (Table 3). Tumors in two or mon loba appeared to be inde- pendent primary ttnnon rather than one Arch Enairon Hrofrf-yvl 31. Dee 1970 T puM0509 TIFL 0305407
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Stat factor in ti full. weight This is what r of lung canc alu;ual cc: sPoKe cigare nreaature de aay think. LC t c :ai.^ns.-t of that cigaret as many as 3 said. Tae" aor`.ality..ra ycar die,.pr 138,ooGCaLt defiaitely- cavity"Ze heart diseas diseases:.whar nevertheless to :.ea.. ou;y, stic, caac_ed us to pinc~oint cigarattes as a ncjor causative d a- tic rise in luag cancer deaths. I prooose we usa the of sta;istics in another way - as an instrisnent of persuasion. I cean: people consider the health risks of cigarette smeung in teras r alone. a^ne chances of becoWing one o£ the estimated 47,000 tics :Som the disease x„y seaw rz,.ote to :ail_'ions of people vno tes. 3ut smo:cers need to be reair.ded tnat their chances of escaping th from diseases other than lcag cancer are not as good as they 'a ni:az^f 11, there was a great hue e.nd cry when .rsersan Foote, e?iationa: InterageneyCouncil on Smociagand Health,decl.ared, es are res}onsible for at least 125,000 premature deaths, and maybe ,000 deaths, in the United 3tates a year. Exaggerated,.the critics r-Heeltti--8ervice-b¢fieves~thasa~estiaatea"'are valid: -'Stn:ler`of""-` ioa.o:.asosersacd.non-smo:cers--~Lzdieate-that-240,JOO.men.rdlt.thia turely_£xtm.diseases associatad..with- eigarette.s~oking_•About~ sreuess osmprecatur6=des;ttisrrfit 5e frcrdiseaserclearly end sociated-witb;-mofdag;::sue3> as "eancer o! the lungr.laryroc, oraL :u ^aad_bladder„as::weT)_^`as+`oroac5itis-;xemghysecu.and.corooary~y : aao'~.2ie=•-102~000:-exce'ss+~or=p=caitiCtre~dec`~hs;villresultYYoor~~ thC:rei.ltionshiiYcto-.ci~ar3....?..:.:«J:~no, ~whilC not. so~obYiolls,.-is+~ ear]y•ir.dicated....;aLs -total-of 240,000 premature deaths apglies' ecause.-ia wst. cases. `.he-dnta, for womea-are iradequate to aa:cr -j'00Z0560 TIFL 0305472
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752 same age and that groups close to the cided that t ceed 4.1 kg selected by other dngs we the limited n major part dogs were p resttictiona w' .. smoking dogs and H. We d CIGARETTE S,1lGK1NG AND DQGS-HA.tIafOND ET AL weight It was most important L, and H dogs be reasonabiy, weight; we arbitrarily de- weight range should not ea- (9 lb). Group N had to be raadan numbers before the trained to smoke; because of ber of dogs available for the f the esperirnent, only eight ced in this group. With these would be left with addStional not suitable for groups F. L, cided to use these dogs (group h) for a pret~'minary long-term experiment on the effects ~of smoking nonAfter cigarettes. Haeed upon pected that h than light d smoke over a As of day previous experience, we sus- vy dogs would survivi.longer s when exposed to cigarette ng period. 7, there remained 86 smoking e start of smoking. 48 weighed dogs; before t 9.1 to 13.1 weighed 13.3 The 48 ligh groups F, L, in group H g(20.0 to 29.0 Ib) and 38 to 14.9 kg (J.3 to 32.9 lb). r dogs were divided atruurg H. Twice as many were put in groups F and L because we sustMcted thak thero would be a high death rate among djgs smoking many nonfilter cig- arettes a dayl . The 38 heavier dogs were put in gtcup h. Because of ing- group h nor group L. ffermces in weight and smok- s not comparable to group F roapa h and H are compva- had the same exposure to ble since cigarette smo of the dogs. taller and la group H do group h dogs died. This e and differed only in the size group h dogs tended to be es .veli as heavier than Within 875 days, 12 of 38 ied and 12 of 24 grdtp H dogs ifferenCe is not statistically signiAeartt. tje mention it only because it maybeotin Group N age, than body weight test to other iweetigatms. gs were hertier, an the aver- F, L and H dogs. Whether aay In9ttettcv on ocntrtenca in nonsmoking dogs is a of lung dtatt matter of groupNd daily. Doing more compe experimental nonsmoking unlighted ci and portly eattce, We cvneidered having "stmke^ tmlighted cigarettes would haw ntade group N le to other groups in respect to rocedures. On the other fuutd tanan beings do not "smokd• ttes. Partly for this reason use of having a)imited mmt- ber of technicians, we decided against sham smoking for group N dogs. The main purpose of the erperirnertt was to determine whether group F dogs would develop less pulmonary damage than group H dogs. Findings in group N dogs have no direct bearing on this question Findings in the study indicate that smok- irtg cigarettes equipped with et&ient Altera produoes lesa pulmonary abrosis and emphy- sema in male bmgle dogs than smoking the same cigarettes with the filier removed, dun- Hon of smoking and number of cigarettes smoked per day.being the same. The rnain question is whether this finding in dogs ean be extrapolated to man. In a preliminary expertmert, we found that the heavy smoking of nonfilter ciga- rette led to pulmonary emphysema and fibrosis in beagle dogs.' This was aonfirtnad by the present study in which we found that a greeter degree of emphysema and fibrosis was produced by sraaking a large number of nonAlter cigarettes than by smofdng halt that number. This dose-tssponse relationship par- allels the findings in studies of human be- ings,ta 27» dogs in this study inhated smoke di- reetly ftom cigarettes. They did not smoke cigarettes in identically the same way as cigarettes an smoked by men. Nevertheless. the types of histologic changes produced in the lung parenchyrna by cigarette stnoking were found to be the same in the beagte as in tttanst in both species thers is a dose-ro- spanse relationship; in both species the de- gree of damage to the hmg parenchyma in- creesee with arcrmsing duration of cigarette smoking- These similaritiee between rrwn and beagle held true when, relative to body wei,fit, toughly the sarne number of ciga- rettee per day were smoked by dogs as are smoked by many msn. For theae reasons, we believe it is reasonable to extrapolate tho findings Irom beagle to man. We conclude that Fndings in dils study strongly suggest that amaAing oigorattee tpit)t an e/rrcrent filfer will produre tav damage to the hrunan lung parenrhyma than smo.Hngidrntiaot cigorettn mithout (rlten. Finally, we tome to the question of tar and nicotine. A cellulose aostate filter such as that used in this experiment removes a certain proportion of partieulata matter from the smoka content So small pm; srooke. Thr different el dogs of ~ cigarettes o entirely to nicotine co: that findin strong suoc group oi : question ac erair=: "'I7 t. tt.e,n~ea. ry od amrbi- ret+aww a.., Nne Ccnvrr dn z rr.e,mw.. dslh nus r Canew/nsr Af 1 Kaha H. aortatity am. ye.n cf ah~ t25.196G 4. Dott R rmoldas: T.n g,it Sted J tf t 5. Au..b.ch smekiee habitch.opn: Ruptt a,ir)<.aine w , ,Yru Eee J ]fr 6 Aue,EecH Chanre ln b.e~ Pmfem mbala to I ity to mr they na to eat or be , availabb I our teemlt Decelnpmr Areh Enciron Aeo11A-VoI 27. Der 1970 T oozosos ~ ~ TIFL 0305404
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~:---.--- _5- nrecise est' tes. F;zere data e.rc available for women, mor`„a;ity ratios for r-.oarable ' vels of smokir.,g appea= to be similar to those for men, but :oz:eunat 1oi-. r. A reasonaSleestimate of excess dea`:js among xomen, added, to . the total 0 240,000 for men, '+ould bring the overa7,2l tatal to 300,000.. I consider 's total to be a reasooable estimate. This situation needs to be driven home to ir.press =okers of their ir.- creasin3 erabiS.ity to sicknesa, disability, suffering snd earlf death. And let us s,a:ce clesr.to our young people that zaon3 men who begaa sxo'r,ing when they were teenag rs, the death rate ii 100 per cent higher than for non-s-okers. Of c urse, there are those who admit the evidence but continue to smoke under the h y delusion that whatever bad happens vill happen to others. statistics an help puneture this "?text Gqy" thcory. If ee are to take the con- servat:ve c-ti.:.ate o; 125,000 prersiture deatY.s a year, this means that every four minutes, s eone in tais country dies preme.turely because of his cigarette smo:ci;ig. This is a r al Amrsiean tra„edy because cost of these deaths could be prevented. To g t people to accept the idea t:.at smo'sing causes them personal harm is no easy s:t. The major obstacles to this objective, as I see it, are the continuing resaure o.°.cigare:te advertising,- the continuing efforts to discredit the evidenc or confuse the relationiaip between cigarettes and disease, a.id the . traditional aoa`-h;/ of htman beings to accept and to act oa new information. Sleve theless, despite these f.iffinnlties, we are making progress. One f the aost si.-nifieanC dcvelopments was tue establishment last July of the aati nal Ir,teragency Council on Cs:3 and Realth to consolidate a•.d coord:.:.ate ti-s=oking activities of the Satioa's lesdiag health and educational orga:.izatio.s. Tae Council's first ?.u:oL'.c -cetir.S Iast,JanuarJ cxt an event of national i-'2ort.ar.ce, :.:dely a.-sd.eXa.:sivel, rooorted. TIFL 0305413 7-002oSF1
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CIGARE7TE S}IOXf,VG AND DOGS-HA.1ldfOND 8T AL 741 ing Dgs 1d his- Averse itcreaee srnoked c rela- :s de- ,,n be .-aofa art;ible ;. then .~,Ticient i ng the not so ueoo- awdel 3: (1) Jtily di- to eize, :,er day Under . nc~elop ai~otoafic d with h used : aation- ship such that noted in human beings. RnckeY ublected dogs to inhalation of cigattttte s ke through a tracheoetottu; his dogs deve pulmonary changes.r In a pretiatitta . esperiments.10 we exposed bea- gle dogs to cigarette smoke irdtaled through ttadteos . In smoking sesaiorts, the poly- tef (Teflo ) tracheostomy tube was ex- changed fa another polytef tube equipped so as to coup it with longer tubing. Potytef ' produotd n tisaue reoction at the site of the tracheoeto A small reciprorating pump delivered t e stnoke in intermittent puffs. In between eo h flve puffs (or mare often when neassary t prevent anoxia), the tube was clamped o allowing the dog to breathe freeh air through is mouth or nostrils Uyon t irt'rtaling smoke from a rmnfilter cigarette, d gs usually showed sigtn of nau- sea and ted in a way reminisoent of the ris reactions o a child smoking his first eiga- rette. This overcome by starting the dags on just an filter-tip cigarette a day; then increasing e number, switching to nonfilter cigarettes d gradually increasing the nunt- ber to the dmired level. Ten txm le dogs inhaled cigtuette smoke in the m ' g and afterttmn of each day, seven days week. The maximum expnsure ~ was 12 ciga ttes per dog per day. Five dogs I died a•i ' 413 days after which the survi- vors were led and found to have advartoed pulmonary emphysema, fibrosis, and en- ' larged +: the glands in the walta of the I bronctdai bee were hyperplaatic and had distended bfet celle.a Histologic changes, including ourrenn of many eelb with i atypi®t nu lei, w'ew found in the bronahial epithrlitcn; no lung tumor was fotmd° ~ The pre iminary experlyrtent inditated ; that heagb doga an euitable for teating oer- I t3in eHMa on heshh of various typee of cigarattet e results aleo suggested that, it ~ continued a tong period of titr>•, the Illtt methodolo might be siaidectory for study- ing the ment of lung tuncrs. How- ever, the hi death rate of the smoking dogs ~ indimted R to haw manY does survit'e for per I long ot tlme, a lwnr leval ot expo• suro was irable than that usad in the ~ nrelimitury e~tperiatntt. I The p nt experimeett was undertaken 1 primarily determine whether dogs smok- ~ ing csgar equipped with efficient filters would develop pulmoftary emphysema and flbrcxie to a lesser degree, if at akl, than dogs smoking the same number of non5iter eig- arettes per day for the same length of time. Materiels and Methods It was decided to attempt b 8nd a aigarette w'ith a diter which removed about half the tar and fwlf the nicotine from the main.treem of smoke when the cigarette is smoked mechant- catly under standard test conditfoea, compsred to amoke from the same cigarette without the filter tip. A chemnt with long experience in this field teat.d sev.rol brande of tOter.tip eiga. reltes for us and designed one that most nearly approximated the pre.iously mentioned speci. fiatione. This cigarette was 80 mm long, with a 17.nua white cellulose acetate filter. In chemi- nl testing and later in the actual experiment, each cigarette was smoked until the ant 49 mm of the cigarafte was contumed (ie, until the glowing tip reached the 49-mm mark). tVith the filter attached, the msoke contained an avera;e of 17.8 mg of torB ter (dry weighU and 1.17 mg of nic°tins. With the filter re- moved, the smoke contained an average of 3e.9 mg of tar and 1.86 mg of nicotine. Thus, the filter reduced the tar by 49% but the nicotine only by 37%. We purchased 480,000 of these cigarettes which came parked in well-sealed boxes, each containing 60 cartons with ten packages of cigarettes per carton. The boxes were smr.d in a t.mpesntar.-centroiled, humid. ifled roaeo until ufed ' Ninelywven pedigreed mela beegtee wem purchased from breedets who stated that the doae wn in good heeleh. They wen kaat under observation in our teboramry for several weeks to make sure that they were in good health. Trachemtomy wee performed an each dog. The tracheortome waa kept open by a hollow polyuf tube. In smoking. the tuW was changed to a polytef tube equipped with a socket for coupling to tubing leading to a cigarette holder. The dogs ranged in age from LT to 3.3 yeara, with a mean age of 17 yeara. They ranged in weight from 9.1 to 17.7 i.'g (20 to 39 eb): the mean was 12.3 kg (?83 ib). Ttuoughwt the experiment the doae were bomed in flve alr- condition.d w.rds, each having 20 ragr. The dogs were fed daily after the afternoon ameking session, a meal consisting of 400 gm of amtmer- cial dog food (Purina Dog G7+ow), wet weight suoPlementd three lima a week by an equal mixture of this and an°ttwr eommeraiel dog (ood (Ken-4Ration). .-. The 97 dogs were aatigned to eaaM in five Arcfs Srwiren FloaftA-Yai $1, Dw t7vo ~ ~05:0495 TIFL 0305393
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» Iy n 6S. If cignrette smoking causes Iunt; cancer, +rhy daesn't ib~-` aru Moner iu those who start smoking early in life 1 . ' If igarette smokittg does cause cancer, why doesn t it occur mmeK- ofte in the lan•n=. rocal cords, and the Findpipe where there is tlte ^ren est concentrntion of smoheittihy Ronld cigarette smoke act ona the I g tissues but not on the other tissaes with which it comes in:, cont et in greater amountsi These tissues are all lined by the same*, type of cell. Yet, even though all of the inhaled smoke must gase s thro gh the .rindpips is extremely rare and mortality rates from . canc r of the larcnz have hardly changed ocer the pnst 13 or 20 yeats -:. ' R ll ncer iD liercent af nll lung cancer occurs in males. For larynx cnnc r the fiEuve is over 90 percent. If tobacco smoke is the eausatire , fact q=hould it not affect both seses alike? I cannot teally take seei• . onsl the suge stion that smoking habits nre similarly weighted. IfA . lun cancer is, on the other hand, predominantly a disease of males, : for i a=aus of constitutimt orgenetics, then patterns of cigatette anrok. ing i:a, be no mote than a coincidental nssoctation. Constitutional tbe--: ort , uttfortunately, have received far too little nttention. It seems to me that thete are so many associations reported beteeeene - cigm ecte smoking and various human ailments that there just cotdd a nnt I nn}• reasonable mechanism which would make all these associa. . tion cnnsatire. It also seems to me that new conditions attributed,>;• to a tokiug are called to our attention erer,r few aeelw. Again, this reeu s to nu a case of "proring too much.° TaLt, for example, the =tnti ical association betrveensmoking and cirrhosis of the liver. Thi is a etronger asaociation, according to the 1964 Surgeon Geoeral's Ren rt, than the association between smoking and heart disease. In t111S tn.itatlce, hORevTr, we do not near 1 great Qeal aDOnt stnoKing cn ag cirrhosis of the lirer-for the reason that cirrhosis has beea , pop arly associated with heavy drinkinee-and smoking in this in. stnn e is t~retty trell recognized as an innocent third party. ~ T e nrincinle is the same with respect to other associated diseases: 4 a iationis~notcau3ation. $. . n„nazerperiments E perimentallF, it is reported that applications of cigarette smoke con ensnta (`tar) to the bncks af mice have produced skin rancers F.e embernoR, this tar is an artificial laboratory product which does not ccur natunily in smoke. The amounts used nn the animals nte ext elc'reat and totally unrelated to human smoking. The amount= of t r u=ed in at least some of the experiments on mice.has been esti• ma to ue ataut eqqqt, tr any compnnson couta oe made at au, ro a m n's smoking 300,000 cigxrettea a day. . I would would seem far mote reasonable to conduct experiments in mbi lt nnimals inhale cigarette smoke into their lungs. To this date,• hos erer. when inhalation experiments with tobacco smoke hace been unc r.aken, the results, in terms of ptoducinR a squamous-cell lungi: cnn r-thekindsaidtobeassociateduithsmokinginhumanbeings-; are eCatin. ' I must alsobe remembered that inhalation e:perimentntion is beutQ dor e on nnimals. In some instances, there has been considerable trauma of ±e sre such that even tf lung cnncers were to be produced I tronld tn t te .ejpirntory system of the animal by the procedures uaed. Somer Irt re to question the edect rlce result. ', C4dnical and atdop+nj ol It is almost impossible t -_rreat detail in liring hnm, mnde in autopsies or fol p;dhologist, I mnke many Some mvestirntors clai, tissne that they deecribe a Also report an tFwintion I A these abnormalities. Fr , htde that cigarette smoki hmgrreas into lung rancer. Ftrst of all, let me say t ,lescribed ns "ptecnncerwn any event, whether or not ~ineerous' is not easr to 'rease in number of celii ,ometimes been termed `prIa.considered as pmancen i•nmmon finding. For ecam ,+f 30 haresqtmmous metap oud only inftequentdy~ sug premncerons lesmn. )fetaf olderrexzonsRberherthev: Calluses on our hands, € erer, rarely develope and i nnd eancer has been obser Dfetnplasia, which has b monly in the trachea-or t-,ncer is esnemely rare. Many observers, includin that significant cell or tis quently than in nonsmoke dwngea and nonsmokete u I bare ernmined thousan nlly. I cannot tell vou ftvm r host bad smoked. 4. Conctwioru The evidence supporting htng cancer consists almost report an nssociation betw, death certifications which a many inconsistencies. Animal espariments do r much hope of cloi nat offer Pathological nnd clinical Asareenltofallthis,It not been proven to be the ce (The attachments to Dr.
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~ speciaf Co munication (5) NOTICE: THIS MATERIAL MAY BE PROTECTED BY COPYRIGHT fA1y (TITLE 17 U.S. CODE) Coronary Mortality: What Is Going On? CORONARY heart dise is the leading cause of death in the UnitedStates. Duri g the past decade, medical and governmental leaders ha e proclaimed repeatedly that n'e are having an epidemic nerease in death rate from this disease. Within the past ew months an editorial in Cirrv- Iorion stated, "Cardiolog sts must be'unreasonable men,' if they are to find a way o slow the rapidly increasiug in- cidence of coronary hea t disease.", The preface to the proceedings of a recent stgraduate course sponsored by the American College o Cardiology indicates that the rate of deaths from my cardial infarction continues un- abated: The introductio to Mediral World Nnra Cardio- vascular P.erieu 1973 co tains a similar statement. A re- cent national television p gram, "The Killers:'Heart Dis- ease-20th Century Epid mic"' indicated tltat prevention n•as not working and m dicine had failed to stop the ri<- ivg death rate from coro ary artery diseaee. The vital statistics of he United States tell a different story! The only meaning ul rate is the age-adjusted death rate, which poaked in 19 .Y and has declined since. To con- tinue to disregard this f ct would seem to be "too unrea- aonable." The Table in tudes the most current figures from the National Cent r for Health Statistics. Figures for 1986 to 1967 have bee adjmned to be comparable with the Eighth Revision, Gtt nr¢timtat Classi,ficatfon that has been used since 1968. Th table indicates the age-adjusted death rate has declined i each decade from 35 to &i yeans and has increased only yond 8&i years of age. The latter is an open-ended group nd the increase may reflect that the average age at dead has increased. If so. subdividing the group would alse eveal a favorable age-adjusted trend. Actual veraua roeta!med Death Rates How can one explain e actual and proclaimed death rates from ischemie h disease going in opposite direc- tions during the past d de? Medical spokesmen have ap- parently failed to diHere tiate between crude and age-ad- justed death rates. The crude death rate from ischemic heart disease has incre in the United States. This is probablyduetoashifti theagtcampoajtioae;Shspp~-,lation Repeint rmtnene 1a CuatoDU awnnY Lemntor3'. W~Ite dlemanl nedb 101 Canter, li_'0 Broaklpn Ar Lus Angeter, CA 900141Dr. tralked. JAMA, March 4, 1974 • Vol 227, No 9 This increase will continue su long as gains in life ex- pectancy result in a bigger population in the older ages, even though there may be a decrease in mortality for ev- ery individual age group. There is a three- to four-year time lag before age-adjusted rates are published. Crude death rates are currently available. National age-adjusted death ratea for 1969 are still incomplete! No age-adjusted death rates ars available for more recent years. Also, re- cent revision in nomenclature has made it difficult to fol- low an unbroken trend for age-adjusted death rates be- yond 1967. Purywseful medical planning and leadership in combat- ing the major cause of death in the United States will re- main largely meaningless unless it is based on factual knowledge of what is going on. There is a need to utilize more effectively the facts available. Necessity requires leadership that demonstrates the vision, wisdom, and firmness to demand better aod more current facts! How can we move into the future without knowing our starting point? We may later learn that the favorable mortality trend from coronary heart disease that started in the early 1960s has been reversed in the early 1970s. Most en- couraging is that mortality from isehemic heart disease of Xetropolitan Life Insurance Company ordinary policy- holders in 1972 was only 93% of that in 1967 to 1971.' Ape-Adiusted Death Rate From tachemic Heart Disease Per 100,000 Population In the United States' Aae. Ye Yeu 331" 45-54 55-64 6S7a 75& ?a1 sse 56.9 232.7 fis6.e 1.62s.e 3a64a 7.069.3 +959 St 6 233.r 655.3 1.6426 3.959.2 7.321.0 '9m 571 238.0 66'S.5 1.553.7 3,434R 1.4104 1961 579 235.9 W9.4 1,541 A 3.18nb t3a1.3 96a ss.+ 236.4 560.4 1.ses.7 s.ea9.z 7.szs.x '9e3 610 240.3 668.4 1.819.1 3.4956 e.165.8 1954 51.0 Y95.6 66n3 1,50e.7 3za8.6 7,865.7 1965 eou 2x6 657.4 +.5u.0 3.422,0 11.0882 19e6 $9.8 236A 861.4 1.609.9 3,413.6 6.nTr.7 t . eo.t.. 2atA.. s4s 1.555.9 a. 4.2 'ran.s :. 19e1 se.9~~. 2su 69a.r tssta s.N1J 11,41111.7 1 55A ~ 2103 96A 5 1.500.3 3.361.6 8A00] 'FrYm vn.1 sen.e,u ar un:esd se.r..- x.e.- m. leea ro wer fplled by 1,1457 to make comparable to 196661969 rataa. Coronary Morta!ity-Walker 1045 i PA - 000476 I TIFL 0305433
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A 124 CIGARETTE LABELLm ANn ApVERTISLtiG you quote him. That is the way this Lhing gets going. They support eachothor. ,1Lr. Foorv_ ,1.bsolutely noi May I correct the impressioa created? Senator 3tontox. Certainly. bir. Toorr. Would y on like to knorv where I got those o•wes? Or would pou care? Senator,llox•rov. I would be glad to hear where you got the fio res. I am merely saying that Dr. Hora is r.ow.quoting you as the authority for these figures. .1Ir. Poorc. If he quotes me, that is fine. I dida't ask him to quote me, and I um not the authority for the figures. Would you care to lmow where I got the figturs? Senator3LoAxox. Certainly. - bir. Foars. ~T got them from the U.S. Public Health Service. Jnd they had plenty of t3me to check the ftdues over. Senator Jloamv. It is intcrestiaR to note that vitaYstatistics for the United States for 1983-that is the latest one ont-eacs that 18,S6G deaths were reported as being caused by l,tmg cancer Rhich originated in the lung, and ?,417 deaths Rere reported as resulting from cancer of the laryns. This would make a total of a little. over "1,000. .1.nd your 9pres are from 1.5,000 to 300,000. Mr. ToorE Senator MoNon, sir; are you seriously implying that I said those deaths were lung-cancer deaths? I can't Irelieve it. Senntor blortnx. Does smoLin,, cause a lot of other things? Mr.Foore. Of coutaitdoes. kbudon'tlaowthat4 Senator Dlosrov. I knon- that this report right here says, aad I use the word "causal," not "casual," there is no causal signifir.wce between coronarv and smokins,r. . Mr. Ibtrrr_ You didn't read the whole thing, Senator. Eacuse me. Senator Dloainv. I hare read this statement more than you have. Not just. as much. Mr. Foorr. May I sey this, sir: The figures that I bave3iven are aot only the opiaion of the Public Henltk Service. Dr. Diehl onmy right is a medical officer with the Americaa Cancer Society. :1sk him. His figures are the ones I mentioned. the higher ones. You will get testimony during this week from scientists with the highest re~+ute,..hosefintttesRillconfirmRhatIharesaid. Senntor lloerox. And I feel sure, Mr. Foote, tlmt.re will hear testi- mony thnt I consider of the highest repute from scientists who might hanDentodisatrteewithsomeofvourconciusions. Mr. Foora Ma' I say one thing, Senntor9 I think thttt this com- mittee, and indeed all of the Congtess, has got to decide whether it is goin,qto base laws to protect the health of the people of this countn• on the overwhelming mafority of inedicnt opinion or upon the medical opinion of what must be re~.trded as a mther strnnga microscopic h~n+tment o f the:lmericnn people. Senator Jioteto_*r. I think it is more than a microscopic fragment. But I will snv this, that- as I said at the outset of the hearings this mornin„ with one or two ,mendments I can accept the Chairman's bill. I am perfectly nillin, to vote for n bill in this arna, even though I do coma from the bi-t-gest barley tobacco-producing State in the country. I will vote for a bill, but I don't want to rate unftirly the iadusxrvoutofbusineas,andIamsuroyoudoa't . Dir. Fovrr_ Thank you, sir. r00.20553 TIFL 0305465 t ,:- Lw .:;.
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?IIEDICAL WORLD ;tuy seem ismo Icros x .y. The lreast d r cnan ei um ® 0 w N I October 10, 1969 NEW VOICE FOR THE SURGEONS: WITH GOVERNMENT,NOT AGAINST IT' I I I
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766 lik~ Nto CIGARETTE S.SIOKI.VQ AND DGGS-AUERRACH ET AL invasions extend from this area down Liebow- for such tumon occurring in human the underlying strorna. beings. We used the term bronchiolaa4,ro- Ccmment renebiofo-alvsolar '1lrmors.-While the ma' rity of cancers originating in the lungs of untan beings are squamous cell and un ereittiattd uranomas, bronchiofo-al- veo r prcinornas are not rare. Llif6cult,v in esti ting the proportion of the latter arises fro the use of variorts terms by different pa ologists. Sometimes tumors of this type ate reported as "adenoearcinoma," not un- r bly, since they are glaadular in ap- pea anoe in many areas. In a series of 2.436 pri ery cancers of the lung included in the Me rial Hospital Cancer Registry, 1,799 wer recorded as carcinoma of specified hist logic typet Of the latter, 214 (11.9 0) we classified as "terminal btonchiolartar- cin " An additional 162 (9.0%) were 'fled as edenocareiaoma, and a few of th may have been bronrhiolar in.origia I a prospective epidemiologic study of cen of the lung by Hammond and Hom,• a d finits aswciation was found between ciga ette smoking and death rates from ad- en reinoma of the lung ("alveolar nrci- no " and '•bronchioler rarcinoma" being ind ded in thia category). Haenstel et aN foun a similar association; the stardatd ized ortality ratio for "adenoarcinoma" of the ung was 26 times as high among man who mokad over a pack of cigarettes a day as a ong men who never smokd. In anoth- er p pective study by Hatttmond.e over I mi11 subjects were traced for up to six yea In a reeent review of the records of that atudy, 47 male subjects were recorded as d ag of alveolar cell carcinoma or bron- chio eereirtoms, and another 199 male sub' of "adatmraroinoau•• of the lung. S for age, the death rate from bro 'oler and aivedar carcinoma was over times as high among men who were cu t cigarette smokere at the start of the stud as among men who had never smoked regu rly. The death rate from adenocaeci- nom of the lung was over five times ae high anio g current dgarette Emokers as among w kers. W applied the same criteria for bron- chiol alveolar tumors as those used by tar tumor rather than bronchroloaioeolar carcinoma for the reason stated by Kreea ard Allant that this term doee not consign the entire group to a benign or malignant designation. Liebow's criteria,= generally acctpted,t•tt are that the tumon are well-ditlerentiated adenocarcinomas occurring in the periphery of the lung; they must be in a bronchiok beyond a grossly recognizable brond,ua with a tendency to spread chiefly within the c+onfines of the lung by "aerogenous" or lymphatic routea. In addition, the walls of the dietai air spaeas often act as supporting stroroa for the neoplaeUc cells. A primary source outide the lung must be excluded before a diagnosis of bronchiolo-alveolar Sur mer can be made. Although the histologic dnractaristics of the brcnrbiolo-alveolar tumors found in our smoking dogs are not identi®1 to the bron chiolo-alveolar turmn in human beings de- scribed by Irebow* the overall picture jus• tifun their inchrsion in this category. Ttrto are several differences. In the tumors found in our dogs, aerogen- ous spread occurred but lymphatic spread was not a feature. It nmy or may not have occurred later had the dogs not been killed. The vralls of the alveolar sepfa formed a supporting structure foi the tumors; the spreed of the tumors was not sa es3anaive as that reported in human beings.r In some of Liebow's ryses there waa a striking resemblance to pneumonia In the stage of gray hepatiration of lipid pneano- nia in which gelatinous or tnuwus material exudes from the surface. This was not found in the bronchiol"lveolar tumors of our dogs. Another contrast between the human aad dog brenchioloelveelar turtorslies in a dif- ferenee of lymphatic and hemstogenoua dia• semination. According to Liebo(e,2 lympho- gerrous metastuee occur in at leasst 50% of the cases. We have not oheer.ed thii in our smoking dogs. Liebow also stata tlut there is frequent Invasion of the pulmonary arteries even in the well-differentiated nmtorar Diarant in- volvement, such m brein, liver, and other orgatn in some human tases of brondtiola aN2r; of ouu more ment fu dir Was :- forme plasi` n,~+t three Ear Invas: acvpic dogs Tlxse i able w'hich man h \atL in Do: been d a)ence autops. \iet, totx9 averai: the :er N8$ ili. years : o;rcfno- dogs a: years o: ?A re• Craiglt of whic Fenned 75e of clvolar. multicer t}pioll; the per Tr.ese c 6ltraticr mon of the neoc of the a such tu: appeara: the liter, the non: ries. In th, tumon : ture,u.i, Areh Ensiron Health-Vol 11. Dee 1s<e "~UU~U519 TIFL 0305417
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s t 510 IMORTALITY IN Sb10KING DiSCORDA.YT TIyfiYS-FRIB£RG ET AL Table 1.-Percent of Twina fn Smoking pisoordant Pairs (HonamekersSmokers) Born in 1901 ta 1925• Men Ybmen DZ MZ oz MZ Na.efu9 r3tlN perG y NOn3moker3 SmOYtI3 NOn3mOka.3 Sn10I4r3 NOn3maker3 Smo4vx NonimoYfl3 SmOkar3 Non3rno4 rs taO <l0 I 66 t00 ... 100 .,. 100 ,.. 67 ... 62 .., 6a 11Q0 I ... 29 ... 30 ... 17 ... t5 D2D I ... 3 ... 3 ... t Totall 521 161 664 21Z • 8, na~per Vr clPrene3 Smoked, \ea, ane lyjeilly. Table 2.-ABe Diatrfbu0on (Pe.renq ln Smoking Discardant Pairs Born in 1901 to 1925 bp 6aa and 2r9osiq Men SYOmen Lasa ESposed- leu E.oo3ed- Non3mok)n5moher Mnre r}p4ud Nonsmoken5m4ke! t.lare FivYSed Yro191 n DL M2 oz MZ oz MZ oz rAZ 1901.1 05 13 14 10 12 0 8 6 0 I t1906-i 10 17 14 16 LS 16 LG I1 5 F -- 19111 ta 20 19 17 22 19 2= 1, 22 1916.1 20 25 2• 27 25 24 24 24 25 ,I 1521-: 25 25 26 30 Z6 32 31 a2 41 ~ Tmel 521 161 la5 66 654 D2 97 53 1 Table 3.-Numoer ef Fiak fPSUs7 an0 Number of Deains in Smoking Oiseordant Y..ala Twin Pnirs Bern in 19C1 le 1925` p/sy6o:ie. Monotysalk Deaths 0aelha Y/p16in11 lotalNE. Non3mEkV3 9mokNit Tot3/Ne. t/oY3mEYer3 9mEkem 1911-19 364 6 10 115 2 2 ~ - 1901-191 iS7 3 13 45 2 3 1901-192 92l 9 23 161 a 5 L.sa ESVo3ee Mple Eipeaed 1911.192 S01 9 14 1901.191 205 4 20 1901•l92¢ 706 13 34 Less E.004" More Expeaea 177 6 3 69 a 6 246 1e 9 e 9y rr SRy and Smnkln{ s1aN3: le! eao4nation ol smokin{ wtu; see Mem6a3 u3Gen el q3tL tlolms amelNrain4uc.U. smoke=a than among the nonsmwkea. Ap from the groupa discua.eetl here there ar several other groupa discordantin smokin habits, namely groups diseordant for ciga ette smoking but concordant or dis- cordant for cigar or pipe smoking or both in diA'eren way.e, illese groups have not been include in the above pre9entation, as it seemed de.9r whether or not they should be co idensd discadant. Table 8 shows TIFL 0305478 7t1020566 ~~ mortality in thoae groups combined. They have been defined ae leea exposed and more exposed, according to eigarette corl3ualptioa The nelmbers ace too small to allow conclu- sion9. Data by smoking habits, ser, zygcsity, and cau.ee of death are given in 7able 9 for twin pairs born in 1901 to 1825, correspond- ing to Table 3 and 4. The numbers are Small and formal statistical tesfing has not been csrricd out Arch EncLen Hea2lh-Vnt 21. Oct 1970
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] .,94I 1.d,]p ~ VO..]1.Na10 CCVVC~ .cNE 1),i3ia I VITAL STATISTICS REPORT ~ Provisional ;Stat~ ANNUAL SUMMARY FOR THE UNITED STATES, 1973 BIRTHS, DEATHS, MARRIAGES, AND DIVORCES U.S- DEPARTIDIENT OF HEALTH. EDUCATION. AND WELFARE PU6LIC HEALTH SERVICE HEALTH RESOURCES ADMINISTRATION NATIO\AL CENTER FOR HEALTH STATLSTICS Roc4ville.Naryland Y085R TIFL 0305500
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T. . . ....y4.,..,~,..-~ .-: .. _..~ .. . Part 3 CIGARETTE LABELING AND ADYERTISING-1969 HEARINGS DQOt® T0. COBtbIIT'PM13 ON . ' INTL+'It,S'1'ATE AND F01i,1IIQN CObiBiER.OE HOUM OF ItLPitlrS}3NTA~Z~LrB 1 . ,,,.1. -- ~rnxE'r4-Fins1 CoxaRie449 . , . . . • . • ON H.R. 643 A BILL TO A/[6ND ?D! /SDP•AAL CIOANNIT~ LADSLINO AND " ' ADYDR[I8IN0 ACT wiru AN6l•9Rr0.1D ¢ItN 4b1LiN0 OI PAC6 "DS OP CIOAItNI•t'Nt• AND PON OTLNM PURe'oW0 ., .. " (A.ui Slqll.r DU1.) . H.R. 1237 A i1LL TD'DID6DL TIIO FIDJEAAL CONIIDNICATIONA CO?WI!- '' SIQlt " 69tADfAOD RNDULATIONA P\ODIDCITI/D CL6TAIN : 9YOADCARINO OP ADYNmIlAIKO OP QYAib1Qw1 ' , ' (A.A 61WMr DUIq . . . .• • ..... .. H.R, 3055 • A EILL DO OZYOIOTDIIY C'ND PNUNDAL G6AR/iTi IABALINO ~ AaD ADYfxirlASO AOit .. tNA• - _ . . .. °c H.R. 6543 1J A DICL lV L<reNU PUDLIC I[NAVeU PROPIUIIION WITH .c C scscP aD claAuUrrN BADIaT:O AAD loA DTpD{ PVAPOACA C/I (AN Au./Ml UU#7 ' ~ N A.YItiL 16,10.17, 13,21,22.23.24, 2•u,14, 20, 80, AND MAY 1 Serial No. 91--12;0 CrlutaV iot fUa 4so of the Commltlca ou 7otcretote uud ibrefpu Commer<e n.w. ~nvwnv.,vvm rn..rt•~n nc.+.n.+ TIFL 0305493
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'--.'"""~ r i' :L •s) MZ , crs Smokers ~ 84 I 1 S : 4 I ! .\ :.SacfeE. i -•':Eaoss.a ! 147 0 9 2 29 5, ' - I Smokerl 2 3 5 a.e Eaaaaso 3 9 bfpRTALITl' ZN SdIO!'+INO DISCORDANT TS9ZNS-FlIBERG ET .4L 511 ~fable 4.-Numbes aE Risk (Pain) and Number of Deatns in SmOking Discordant I FemalaTwin Pairs 8orn in 1901 to 1925• Oicytelic Monntyaollo Oeatba Deatha Tr CI elrth Total Np. Nonamokm SmekOSt Total No. Nonsmpkera 9mak.M 1911-1925 SID . 6 11 213 4 2 1901.1910 174 11 6 59 0 4 1901-192! 68a 17 17 272 4 6 t.eas E+poNp More tupoaeo l.ess EapOSSO Mors Fjposeo )911•1925 668 6 12 262 4 2 1901•1910 193 12 a 6a 0 e 1901•1925 761 18 20 326 4 6 • ey rya9w ano smpkm6 status: tpr aap4nation of anwkina status. Ne Melhopa Nction ol usL ( FormM e pkarein{ludea. ' Table 5: Nvmber af Risk (Pain) and Number of Dalbs Among Nonsmokers : - and Former Clgantta 8meksn• Diaytatie Deaths Deatha TeLlNO. Nensmokers FprmMSmNan TutalNo. Non9mpken FormerSmokers Men 146 2 lo - 60 2 2 Y.'mnan ]22 3 3 57 1 In empbn discerd.nt twin Nin bern In 1901 to 152S by ryaoany and sas. able 6.-Number at Risk (Pairs) and Numberol Deadns in Smoking Discordant Twin Pain Born in 1888 to I900' DiSyaota Monoay8pue Oealhs peHhf Total No. I Nonalnokan SmokerSl Total Np. Nanamakela SmCiMar Mn 67 22 17 39 5 4 WaTell 58 8 9 14 1 3 laia ExppNe MOM FJposeO . LoN EapoNd Mary Exttote6 Men 89 30 22 60 5 5 ~NOmen 58 8 9 18 2 5 • By fu, zya ailT, aM Mlpkin( Matus: tpl eaplanalqn o/ fllloklne StatYa~ 0a0 Metnopa 3ap!•9n al tN1. t Fprmer am Mr. inNUOW. Table 7-Nrmber at R/ak (Pain) and Number of I Table e.-NUmber at Rlsk (Palrs) end Number or Deaths M M e Twin Pa)rs Bom /n 7907 to 1929' Dasfbs in ldale Twin Pain Benl 1901.1925' Deaths Clpr and/Or NOnamakars Pipe SmOksrs 12 4 ManOlye4nc DNtns Total No. Laas Eaoosep Mure ~pasao Oltyeotle 112 3t I: Monoay8olic 55 1i lf • DiscorpanttorCi`areRe LnaYina, tlutenn[araanlar a/uerpant tor e1Nr or Dipe amuki n8 or oGtn In aiNerlnt 66 3 2 -tCOrorury hnrt diNaaa. two ussa; acrJp.nt ane I use. • Dneordsnt ur elpr Or pipe smeklna or belh. t oWaes. iGnesr. / C.prONry hurt aliNaN. LL -70U,zOrJ6"y (.... Arch Environ HaOtth-V6Z 21, Oct I970 E TIFL 0305479 t- t. 3
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Part 3 CIGARETTE LABELIPIC AND ADVERTISINC-1969 HEARINGS DBIIO[D TBr CO)S{11iITTEE ON INTERSTA,TE AND EOREIqN COMMERCE IIOUS~ OF IIEP1tESEN`PATIVES.::,=1,,,, ' . .,,I.. : . NINNTY-FIRST CONQRES& ' . -BIRSTSWSDION . . .. .. .. ON . , . li.,~ . ..v.. ..~,I ILR. 643 A DiLL TO ANUNU TDD FYDRR.IL CIOARflPTB LADOLINO AND ADVYRrISII/Y AC[ @l2n RD/IPUOI' NO SIIB LABSLINO or YACIC- AGCB Ol• CIOAUilTDl. APIDYOR OTDCR PUiP06BB . IAW 61oWr DWq H.R. 1237 A DILL?0'DIRRCF TnD FKDNF6L COWIUNICATIONS CO>1nI& 6ION 00 F.91'ADLISD nF.OULA?ION6 FROn10D[INO CORTAIN' DROADCA6TINO OV ADVF110161FO or CIOA3OPID6 "' IAnu 41.11.1 DR9/ . IUL 3055 A DlLI,O'O BlBt11O6'OPN RnD FIMDDAL C1Oei11T1 WBOLINO ABD ADVDRTIBINO AOP . Und 61mll.r DY1.) . . . .. H.R. 6543 a BILL BO DAPBND PUBLIC DDALPII PDOLDOn0N NITD R®- 6PICP DO CIBABDFtB DdIODINU AND lO6 OSDOn PUBPUDD6 pnd D1sILr DDi.) APRIL 1D, 1t 17, 1& 21. 24, 23.24. 26, 2& M 30, Ai1D MAY A Serial No. 91-12 Pcinted &t the Dae ot the l•ummlNee ou lOtecWte Bnd FOre/Qn Cunmerte n.M. nnCCnvYC)IT nnrNTlNn nr'NI~ TIFL 0305497
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!Y A f t rzi of ccn• .::ouy con- : :,nnw,llY -in;?,eforo ~ ca smoker< ; of a mmt ~ ,ponsibili-. i ~r as for a 1 - -lic Health ~ •<pectnney cesmnkers j !r,ulce more ~ =hon•s th:,t 1 11 packages frequently t ich is rare ~ uoking ;u i ~ s ble for ~ .- sale nud t I!eahh hnc . rhe health ~ ey smoke ~ = to protect I . cltemtcals ( mission to ~ are nn_ ~ i ify nico. + .: tu•esenrn. p F of Cnn- : ;s uf the t. _,inst the ./21 The l -~eitful.nr F ..her nrno- i ';i1 Imlie,ros t hnziu•ils nf j- nur fno1+ ' •i:ots that f ~ ~.n•tl" anrl_ ' ' ln untnkn } ,hat "tbe t t CIGARERTR LAH8LLV4 AMDeDVERTI5LY6 I`L.3-3 To fn to provide such warnings permits smokers to rationalize and eneoura children to believe that if smok3n: is really bad for you, dio Go,ernment mould say so and would not permit the -inds of ulverti ments of cigarettes to which they aro exposed evors day of thcirliv s. We ieve that such warninp vrill diveourna smoking, particularly among me of the boys and gtrls who have not yet becorue habit¢ated tocicntr ttes. - Your committee, therefore, apparently faces a basic issue as to .vhethe in a democratic capitalistic society, human life and health cnn be 'ven precedence over financtal~a~a for those who produae and sell a p, duct which the highest health anthority ia our Governmen6 statesumjurioustohealth. •. Sena rHnet: Tbankyou,Dr.DiehL - . . - . Sena rMortoti4 : ' Seua or MoRmx. HIa Foote, in your smtement you tell the com• mittee, `What is scientifically sound.' Have you any background nsasci tistt . oora. It seems to me tlmt I have the sante right as any advoo- , 3fri - cate, or attorney, to quote the scientific figures, if rquoto tlrem-ee=-- cutatel . I notice no hesitancy on the pat•t of the members of the. $ana rs;Siorrox lny I don't quastion that at all. I merely want to know if ou an a scientist. Mr. ooan= No, sir, I am a layman. I ata only quoting acientisb. _ Sena or 3Eoatoa. As a matter of fact, in Advertising -A„"e some tinte a you are quoted as saying; "I am not a scieotist; I am not a . _ scionti authority; I am a pro dist.1/ I heve nothing against that, ei her, because to be in po •t~yoa havs to be a little bit of a pE19 latindisto: _ . . ns ~tn wlto speak thea w~t6 of what thi'scientiats -. - P e~ savtot epeopie# Ur. Perhaps a little more than that~ sir. I presume to speak as the rmer chairman of the e:ecntiw committee of the American C¢aeee 3aaiety and as tha chairman of this counciL I presmne to ap¢al: the members of this couneilt both scientists and lay leophe, atn It nlitGemorethaapubiicrelnttons. Sma hfoarox• Your trackcroand prior to your present :~~eooia-~ ' tion intheadmttistt ~-Beld4 JIa otme. Yes, sir.• for about 3;tfz naes. Se or3ktem:4 Witha.cryrood~irm. '- . ... . I fr. oore. I think sa ;•IcCatm-Eric3ann, and one called Foote, Coned: elding,nhichisnorvonthebigboard. Sena or Moemx. Did illcCann-Etickson have an account from ; . Durhn il.C.i , hir. uars No: but they had cigtttbtte acconnts nrouttd the wortd. . nntl I as one of their laruest stockholders. I hm-s been to Durham. Sonaor3lotrm.r.Dr.Horn,s'hnwnshereafexmumenten,o,rend- . _. in„ f the New York Tinu~s, of Febrnat;v 1R af thiH ytvtt: he aid. - ilu0rlR you as his aathnrit}'. ".1t trast l:n,Mw, Pn•omtnse .1..1t.w kt.:a }•car a causmd b9 smokin_:' This intere+ts mn, that tha scientist. thc d tor, shmild be qnntiny you, the ndverti+in; agent. I sttppose TIFL 0305464 ~ . T00%:Q552 PA - 000482
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t a-1 win Regi,ter The Landon School or H,giene f Stedical Oenetiu . and Trapirat M..licine London r .,.. •.,-~ A Twin St~dy of the Influence of Smoking on Morbidity and Mortality The Danish win Reo sccr, which comprises all twins born in Denmark benrcen t87o and !gao, as becn used for studics of selected problems in the field orepide- miology and p bHe health. This report gives a survey of the preliminary results of an invatigat on of this type, which intends to amplify the present kntnvledge about the possi Ie harmful cffccts of smoking on health, by taking adtiantage of a twin material ., ich makes it possible to keep the genetic factors under control. A series of 62 MZ and same-sexed DZ twin pairs, which had their smoking habits mapped - 1959, has been followed eootinuousl•v, and the mortality which has occurred in this group has bcen analysed-in-rel:tion-to.tobacco consumption. NeitherliZ nor DZ paits showed-any tcndescy.to increased mortality in the header-,sntoking cotwins When the material was subdivided according to cause of death, no conspicuous Nception from the general pattern was found, but the subgroups were relatively mall. The distribut on of selected diseases and symptoms, mainly of the cardiovascular and respiratory yscems, was studied in this and a second series, followed since 1966, with a total of g8} pairs. • Fatal corona occlusions and nonfatal occlusions, diagnosed in hospitals, showed only a slight an nonsignificant tendency to be associated with higher tobacco con- - sumption, and i\(Z pairs where only onecotrrin had had an occlusion, he was equally often th heavier smoking as the light or nonsmoking one. Astgina pectoris was significantly more frequent in convins with higher consumption of tobacco than in those tsith to rer or no consumption. A similar significant associatioa tvu ob- served with resp ct to chronic bronchitis. Intermittent claudication of the lower extremities sho.v the same pattern, but the differences beta.•een heavier and llghter smokers were s s marked and did not reach the level of statistip1 signincance. Symptoms of p ptic ulcer were more often reported by the cotwins having the higher tobacco onsumption. The follow-u of these series will be continued and provide a broader foundation for an ecaluafla of the influence of smoking on morbidity and mortality in genet- 33J n.v c.a.'. at.d. c.nwd. trvt4, u. sas•us TIFL 0305483 ~-QOKU$71
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°~ ~z Parf 1 CIGARETTE LABELING ANA AllVC1tTfSIP]G-1JGJ H E, ARINGS 11KV111114 TIIN OOhI h11/IY1Il/1h/ ON IN'l']U38'1'A`I1113 AND 1!'0].t]T[GN C0MMEM01 HOUSE 0I? 1iYPIt]PSl/]N:L1A'l1IV]I;S j'IIN];fT-RIItS'P WNURRSS „ .• FIRS'1' NId&4ION ON ILR. 643 - A DILr. TO ANKN TRN FSDn1lAL C10AKNrrII L.u16:L1N0 ANN AUYNIp'IS1NO AlT' q1Y1I IIKNI'KIIrS'OUY1N I.AIINLINO OY 1'ACr4 AUTAY OM CIl1ANN111'SS, ANb YUN Irt'llKll 1•UIN•UN1.9 ' IAuA NIm11.r 1111b) II.I2. ]2:17 A 111L7. fCU DIIINUr T11N MNUNIlA1. 1:UN111/N1UATlllt/9 COIIAII• 1110N rfO ltyl'A11/.IN11 ItWAl11f.AT1UNN 191OIINlUNNU Clill•1'AIN DNUAUC.1NfINU UY ]UYNNfININII OF l'rU111N3IJ'NN /And Nlnll.r INIle) II.R. 3055 A D11J.ffO/rTIrDNOYN/1N rl'11N FKUNYAL CIOASNTTN IdVDLIKO ANO A/1YS11'LISINU AOC (,1nA NIMI1Ar 1111b/ II.R. 6543 A RILL SO AAT/INU PUIIr.IC 11NAfA'11 I'NpYWT1ON \YITIt IIM tlPBOC U'O C[OAN/TITN NNIII:INO AND FUI{ UTIIEII rUlll•O5L'9 (Au,I SIroIMr 11111.) . AI'R1L i6, 10, 17, lA, :1, 22,':/,:4, 22r, 23,20, 30, 3N1) MAY I Scrilrl No. 91-10 1•rlNiell for lLo use of llm Colnud[leu oN I nler.hlla KNd ForeICN Colnmerce V.6. OOYVIIN\II1NT 1•1116TINO OFVICN N-90 \Y.1:il l lNO'1'Ua I 1110u
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/I ~ .__...._.._-_ CIGABETSE LABELL\G A.YD ADVtn'fI=G .133 d back .°oote carlier, in :•.as not implyiny =cr. •st 125,000 deaths ufisyou nre taik- „son tries to lialet _. "500,000 people •-ic heart di;ease~ lung Cancer, GII{ . dd them up, pnu nchitis-lung dis. .~,c, they say later . ucameen cigarette _ 3,000 come from Y - ete is ao proof nf -, and it thini ; the n1 relationship, if -rour 125.000 came adsateII.Iam. 'n't ma~•e up the 'iltSer~ce. This ...:ccptioually low 'i an nmatenr epi- _ accountsforpart 'icntific man here. II.S. Health Do- "dor if we could ,h"'e figuas came t eot here. They ~. Perhaps at this :formation before r sclmt their c?ti- _hborlwod of tLe ..v contact is Dr. ,i!, nnd al_o chtot ...rica Dr. Guthrie talkal with his o:cn scientists, whom I do not l=2on, but he had quite a bit of time to work oa this, and he iurnivhed me with tleese lie^ures. I I icould also like to point eut that I had these in my speech, which was cleared with a numixr of phy;iciuns in tbe Public FlctitG aen-ice, and that I used the fiFures in front of 9 out of 10 of the members of Dr. Tcrry's udvisory eommittee, to wbom carly in the meetiu.g I said, "If you don't li!<a auy fie Ics meuioned today, please spea's up," They didn't speak up. Senator Haa•r. I wonder if Dr. Horn has any figures lie would IiL-s to state atthis point. . Dr. Hox-~r. 'l:he Bgpre of 13-a 000-whiCh is a very low estimate of the totall number otdeaths^-wiiich represents the excess number of deaths, occur in cigsrette smokers aver what wonld have dccnrred if they were to die at the same rata as pw~le ~^.ho hnd never smoked cigatettes. It ceus"Ists of appl}tinF the 1fl62 death rates to the diseases in which a enusl relationship au been indicated. Thesa include coronary heart disease, lung cattcer, bronchitis and emphysema, catuer of the oral cavity, caacer of the esophagus, cancer of the luyns, and cancer of the bladder. I am indebted to the oririnal set of figtu~es here, which have ap- peared in stAtementa of the 1'ubllo flealtd. Scrvice as long ago as last .lugust, and to Dr. Levin, who has published these figures altd is, I believe, scheduled to testify tomorrow. The aumbar of deaths from coronary disease, which is included in that, is approximately SO,000. The number of deaths from ltmrn cancer is 38,500. The number from bronchitis and emplly~.ema is 15,500. Canoer of the oral caritr, esephaa~us, latTns and bladder, add up to 8,002 T11'v lotals 1"S,C~O, which is a little higher than the ortginal estimate of 123 000, but is based on applying these to esti- mated 1063 deaths from t~tese causea , This 5gtue is obtained by applyia~ rates anly for thesa specific diseaxs and only to man, sincs tlit bulk of the epidemiologicai studies which have hean done have been done on men. . Senator 3foxxox, May I ask the Doctor one questfoa 1 Senator Sser. Yes. Senator 3lomos. I am a Iaymaa What has cancer of the bladder gottodonithsmokiagcigarettes? Dr. Hoarr. There is a~creat deal of epidemiologi.cai e~•idence indi.- catingthataancer of the bladder- Seaator 31omx. I am,qoinc to quitright notv. Dr. Hoav. Is higher amon„ cip rette snrakera. I tltink you will Ond in the history of carcino;enesis that the bladder is an, orantt of !he body thut frequently corwentsates carciuo;,enio matercnl before it is exemted. Therefore, it is particularly sueceptible to activity by caminogeaio substances. . Senator Moatoci. I am sure gettingnn education out of tlsis luariug, Lvillgparnntesyouthat. _ . ScnatorHAa•r. Senatar7lnminiclts Senator Dnsnams. Mr. Foote, I have really quite a lot of problems with these figuree, hut I dun't knom that tLis really mnkd very muclt difference. . . .. .-. , T opw0556 TIFL 0305468
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One of the re glaring areas of inexact diagnosis as d onstrated by autopsy is coronary occl on, cynioally regarded by some as a"w ebaskat diagnosis" for any inexplicable su den death. The following case history in 'catea how an autopsy can correct the dis osis and enhance accurate statistics. Case report I received a lo g-distance call from the hus- band of a patien who had died suddenly the night before of a'maeeive coronary occlusion." The couple had be n eating in a restaurant when the patient clutc ed her throat, became cya- notic, and fainted. A physician in the restaurant examined her and guessed that she wes the vic- c;m of a massive pronounced dead who listed the ca ronary ocolueion. She wsa by an ambulance physician of death as massiva cor- The husband repnrted that onary thrombosis. his wife had been had wine, preced had a history of drinks. I sugges fonned. Later th had found a slig llttle alee. Thar cause of death to asked if he had c ported seeing wha in !he larynx, as He waa asked to r a few minutes late of steak which he COMMENT. T history isthe rol nation in pointin might have bee basket diagnose should be a spouse of any taught how to The physician that she had cyanotic immedi that a person w eating steak sim candidateforim the larynx, the Manual removal omy with a r saved the patien Had the fa diagnosis, anoth nary occlnsion Wit.hout auto topsy--we cann eating steak at dinner. She by martinis. The patient equent gagging after a few d that an autopsy be per- pathologiet told me that he tly scarred heart valve but fore, he was changing the rheumatic heart disease! I cked the larynz, and he re- appeared to be a small clot the patient bad bled a bit. heck "the clot" and returned to report that it was a piece occluded the airway. e significance of this case of the poetmortem exami- out how the woman's life saved and how waste- are still common in what cientific discipline. The hronic choker should be medy such a condition. the restaurant learning ped her throat and turned tely, might have deduced o had been drinking and taneously could well be a ction of a foreign body in -called "cafe coronary." or an emergency tracheot- urant knife might have e life. y accepted the original false statistic for coro- uld have been recorded. ~--caeeflil, thorough au- expect to learn the true incidence of "cafe coronaries" or even the true incidence of coronary occlusion. Comment That autopsies often correct diagnoses ia not so much a reflection on the state of % diagnostic medicine today as it is an objeo- tive commentary on how much medicine ~ still has to learn. ' Diagnostic medicine is continually im- . proving, especially with such refinements and improvemente as ultrasonics, electro- microscopy, isotope scanning, arteriogra- phy, serum enzyme studies, percuteneous intracavitary electrocardiography, per- oral intestinall biopsy, and even biatrial intracardial phonocardiography. But these valuable technics, unfortunately, are not readily available for everyday diagnos- ti®. The equipment is expensive, and in- terpretation of results is often difficult. Even when such highly refined technics are a standard part of diagnoatics, there might well continue to be a lag between diagnosis and ultimate c'onfirmation at the autopsy. Until the unlikely day when diagnostic medicine is close to 100 per cent accurate, there will be a need for the autopsy to cor- rect, aa well as to con9rm. Beyond that utopian day, there will be a place for the autopsy for its contributions to our under- standing of disease and the evaluation of treatment, research, and tissue and hor- mone salvage for the living. This should not be such a revolutionary concept in a society which prides itself on the high quality of its standards of medical care and research. In Soviet metropolitan hospitals, virtually every death is examined at autopsy. Even when a patient has died at home of seemingly evident cauees, rela- tives frequently request an autopey." Professional resisrance or apathy to the autopsy is still an important obstacle which cannot be ignored. The practicing physi- cian must be convinced that routine post- mortem examinations will enhance his own medical knowledge and diagnostic skill. Moreover, once he is convinced. his success in convincing the next of kin to give per- miaeion for an autopsy increases draroati- cally.- The participatton of the clinician in the autopsy today is widely regarded aa in- cidental. This is unfortunate, because the autopsy enhances the skill and knowledge August 1-196J / New York State Journal of Medicina Zoa3 TIFL 0305427 I I {'
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r 512 dORTAL1Ty IN S]fOK!\'G DfSCOCD.aVT TWL\•S-FRIBERG ET AL Tabl 9.-Cause of DeatA in Smoking Disoordant Vein Bern in 1925 by Sex and Zygcslly' Men Waa.n Omyeetie Mpnury{o5c Oizyap6e N.e-esyentie Net . Nan. Noo- r nom Smcaerst amu..r. smas.rst-smww Smown. moses 5masersn ra a a t<fa More Lel3 Mpr. l.r. MGre Ler. MP/e Causs fnwtn Espcsed Espasee exppssG EspcasG Espnnd faposee ExposeC Espwed C:roneryh anals.ue 5 a 5 6 3 2 0 0 Gsspro.as u4•Cisans ~ 3 1 1 1 3 0 1 nncsr cf s Wna o a 1 0 0 1 0 0 pnce.,oan rform. 3- a U 1 8 7 3 3 sm6das 0 2 0 0 0 2 0 0 aiCenh 1 4 1 1 0 2 0 t omerwuse 4 6 5 0 6 3 I n .nc.uws 13 34 14 s Ia 20 a 6 - FO. eaP~ nalion of sman:na atatua. wa MethCda %CnYn of leal. t rormer rnaa.r. inc/msa. 'hhe el I11ort.^.11ty of emoker5 in the able that the different results in the two male dizy otic group is due to several causes graups of t.vim are the consequonfx of dif- and {tis ot possible to associate it particu- ferencee between ostnokers and nensmokers arfy a-i any specifie dLsmsa Of the total in genetic and other factors aseociated .vidt number o 21 cxce.5s dcaths associated with the twins' behaviur and exposure to physi. mol:inr, three w'ere caused by coronary cai, chemical, and social environmenrs. 1~at heart dis asr. Four case5 were due to cere- such differences exfst has been showni= bfovaxul, r diseases, one due to lung mr,, In most of the analyses iormer smokers cer, five ue to other forrrs of cancer, five have been included amonR smokers. The due to sui ides or accidents, and one due to separate analysis cwrrird out on former ther ta smokers sltows that this approach is justified One m ue of hutg cancer occulaed in a atlesstformenbomin1901to192at male mon zvgotic twin belonging to the less The results for the women are inconclu- xpesed g up. Four suicides or accidents sive and to some extent contradictory. It is ccurred mong female dizygotic smoken obvious that it will be necessary to obtain ompared to none in nonano:en, information from future follow-ups . In this analysis it has not been possible to Ccrtttaem associate the extxu mortality among male, dirygotic smoken with any spcriRc cause of 'Ihe n ber of deteesed tw'nu in sawking death. Several muses contributed te this iscordant pairs is small. Only time will exces mortality, but the numbers are still how whe er the trends found in this study too small to allow Lonelusions. There are re atable. Howaver, even now the data sug- cetain findings, though, which are intrigu- rst that the differences found have a ing and worth point'vtg out. The four ®ses i7nificaat biological meaning. There is no of lung cancer among diz,vgotic men oc- mdicltion in the present data that the dif- curred only in stnokers. Accidents and sui- erent rel tionships seen in the dirygotic cides taken aa one group seemed to be asso- mups co pared to the monezygotlc groups ciated with smoking in the dizyRotic twins, erc cs d by differences in smoking hab- partiLtdarly if the dam for both man and ts, or age distribution. For both variables women were combined. This finding is of ~f?ry simi4 r distributions were found for the interest since, considering the nature of Wo zygos ty groups. It 5eerra mcre resson- these deaths, it supports the hypothesis that Arch Environ $ealth-.Vol Tb Oct Z97D o 7-0Q056g smokin; pemlu .Sur.u Suggest srooker factors Itu' 1. TA li< 13ec Dept o: Hadth : 2 I{. mis ol ledK E CM1.on, Hes1;h, Senice 1fl66, p a.r. Reppn Cenef c. C m! S oE Slu 5. T vith p to cer frcv, r her CS epi:au w{ih r aal C. x,.f:: z. c aatid gira xaelf
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PARLNtAL SMOKING u tY asl n t r.t 1 n(.:.rv•..uii't I u u I nuawwtu .Id s ~ o n..nun O YM ~ ,o u.. cw... 1a s» A 34 » I n.aar.n..r. u a N' 1 .,I(a(MpM Y„lMY{qY tpIWIl01l.Y FM \.(la. na. a. /Htr u.pN,.Y(w..t i..p.wq. u1.Nlna 1. wex,nnl ui.tliq Y.ytR Tha ncideaoe oF ppakmeph[ita, abruplio noosaokeea. Furtheneeee, this lack o( signi[- placen and plaeenta pmia did not show Scant diRa:eaee wae pracat whcn pe[inatnl a dfr nlation(hip to the aataunt s(ooked; motntity wu divided lnto aaonatal deaths how , when. _ . the patkats were govped as md adllbictht. The petinatal death nte in s~ke and nmtonokers, the smkas bad a premature intamn clasaifled by bi~th weight, ei8ni6e t)ncreese (p < 0.0!) ~~ was ei=aifitanty (p < 0.01) bwa among eomPll tltuu. No sigeilleaot (P > 0.05) e8. ~~n, . !ea w demonctrated whh b)peesm.ion ,_ To exoludc the known in~ocaee of race wieh a d whhoae axeml.. ~l. 3l~ .. en. birth v~eiSht, pmienu weta tlauided as . . . .. ~ bkthsi 3 Caucasian or otha (TabL 4). There was a bghec pereentage of r....,...pr in the teod- enta and the heavy smoking 8irrupst'this hpot fhould have wnttibueed «lati.ely heavia iafants. 7Lh maka the tamof af the IiQhta birth weishts aaompaekd by maternal smoktag evea mora siydRcaaL Maternal smokiap.did aet rigni6amtly adat the mode o( ddiveryt the cesarsaa sae- tiea rate was equal ia all Oroaps (Tab(a 5). TIMN 0154234 TIFL 0305512
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~ 774 ~ Crsr.rcccnl ~C¢at oe {'tcroa B. Bcn::g. 1f.D.. Sr. Taar:ra Hoarc[]l, liaaas.at>dc CRT, SIO. Callega ed4catlon: Southwestern College 11Y39-77; liansa.e Uutirerstq 1v^7. d B aegree. . . Stedldne 1/U0-Si: ]LD. degree..5: ][edicel sc aol: 8aasas UDirerri4 BrSOO] of Iutarnsnlp au nsitleacies: ln[erny8lP Annaer Hoapital, St. Paul, lltan., 1dya..,~t ;~ Ioy3: Reside [ W aediccine. dudter Boapiwl, Sc Paul. Sliaa., lxi&-i8ae; Ren4 a;uc iu Pstn logT, Geoenl Hospital, Saaata Clq, Slo., 193g-19e8. Speclalty rsl5oaelon: dmertcaa Board of Pathology-PStholottc .lnatomy,ar. 1W1: Ameri a Dnord of Pacaologr- Hllinical Pathology, 1'Jf& T, Hnspltal e polatments: GenenL Hoapltal SC., 110., Pathotogla4 1eie-195e;:n St. )largure[' HOeDlta4 SC•. SS., C4aaattla$ Pathologlst, 1ai7-1a39; Proaldenaw s' Hoepiral. %. .. Ss„ Consuttlng PathologisT, leCS-Dreseat; President ot )tedial'.:StaG. L'.Aa; oeen o! the World Hospltal, 6.C., )lo., Canaolting Pathologla0.:.:; Ipei:~7JK,I rvetdent of lledical SIaR, 19aa; 3a Joseph Hospn.9, &.C., 310.:,.Y Pnthalo, st. oJtl-Uresenc 4 )lilitarr d ty: U.3. Naral Dispensary,'lYeasure Istand. Californla. Juae 19i2-' Aug. 1tKl; .3.3. Retie), dug. 1Nt-Jaa 19LS; U.S. \aTat Hospital, DuDha,• - Geor~ia,Jan. . Preseot S ms: uapcaln, Hedical Corps, U.S. Sacal Reserte Unit -No. S-46 S.C..llo. - 11em0erh' in proteaslonal medical organlaations: 3[ember, Jackson Connty..~ (\Iteeourl) edlcat Sorleq; wseouri State 3ladlcal dssncuttoa: emedala lted-;ec Scnl Sseocla on: Southern Medical lSaoClatlon: Fellow, Amerieea soclety of Clinleal Pa olegists; Amertean College of Phyaiciana; CoLLe{e of Americang Parhologtsta lfemaer, futernatiooal dndeIDy ot Pathology; Academy of 8nrr i l H t BL • aa 0 cln dsaec a md rican Thoracla Sodet7: dmel eneic Sd ; Ame Banls; dm rlcan Therapeutic Sotled: Fellow, faternattonal College ot S Seooa; Item t, ]tlssuurl SCCtety of Parhataal+b: 1alCCfate Ilemhee. Sa Socieq oC iLOloglsb; Aseociata.llemeer, Siaaa Ctq Soateq ot Internal 31 tclne: 8onn ry NemMr. Jllsaourl Socieq of Hedleal Tachaologaats; >fembv Snnsas Ctt Scademr of Medicine; Saabaa City Southweat Ctinteel eodetr:. Sensea CI Sneieb of PatholoPlata; and htlsaoarl darxlatlon ot Bloud Rattki IScenaun Sansae, 19341 ]Bawuel. 193T. Teaching pl>ointmaata: Aaaociate CI1nWel Profeasor of Pataolup and On Lnlce ity of 8anaae 3ehooL of 3ledioae, 19g2-preeai ogs . ]Iedieal s cietr actlvLtlea-Y1Gasuart 9tate Medical Assoclatlon: Chairmaa the Conncll li3111,1982-193g; Preetdenteteat, 1938-193ri; Praldee6 1a33-1 6aasaa 3ontDwaat Clinical Society: Preaideat<lect, 1eEg-19aT; PreeidmC•. 19i7 :938; aneas Cttr Socleq nt PatSolaa7ata• Prasldeat, 1952; 3~4: 6a rLV Rina C.Id • Exeeutlve commlttee. 1948-1969: dmeriGn Society ot C1fl Pathoiogie : 1lemner, Doard ot cenaon, 19e5-1939: cbafrman. board of cen 19Sg: 3liss uri SocUq ot Pathologlan: PrddeatalecL 1gaT-1A58; DnstdeaC 10::s-10a3; L'ege of dmertria Pataoleglafs: Boara ot Gorernon,193a-1ea1; TI 1 -10eS1 penldeatelect 1ge1 13gg; aIId Dteldeat, 1e93-1995. Drealdeat , Pubtlntb na: Errehxeblaatoela la Dlayaotic Twlae. J Ma 3t. i. ge:108, 1ga2: ._ Bacterium 'aerephoraa Septlcemla ta 31ea dm. J. CB0. Pata. 1Y:See, 1915: marologtcnl Condlttous P[eralent ta 2t0plal inaa: Treatmmt with Hear7 ates of Ll rlolet Bay, II.S. Vaval Sled- HeB. 45:119g, 1PS4; PatholoTy of cenome of t e Cerrtr, S- C. Med. Jour. 18:Y, 1047; The Ocearnaee of End T.plma Fe er in 8aaaaa Ctty,'JfissoarL J. l[a. )fed..laoclation 153g'f, 1pa8 Changing aeeob oC Carcinoma of the Cerr1; !al J. ooa ,tt Gy'a 66:112, 100 " 1951 • Gangrene of Fatal at cal Acid Fast Infectioe, 1m. J. Path. ZS:T5.7, 5crotum m a Cumylketlop of Ret[oDeritoaeal Infactioa. J. Ctoi gg:188-0.'t. 1953 Huaun I tlon x-Ith abpleal Aeld Oegadma. lm. J. Cin. Path. ?8:8a8-m: "' al E 1933: The ltnral Ctlaraer.rlrttca and snlmal Pataogeaeeiq of ea AtTpic -' I Fast lThich Caasea HaIDaa Dbaae, Aat Rev. Tubere. 71: Ta--e7, Fatal Ccm cations of Retatirelr Trivial Ialurfu, Proe Nat'l .lnnm of Coraua; -" 1e53: Cn a Ilonosfda Deaths. fald. 1036; The Health i\eeda at )HSeoari, eunrl ued. '113-18. 196a t Ruman infeetlon tyith ^Tellow•' Acid Fast Saelllar ' ~ ~nuual nue0. am. Ber, lbaese- 73:p17-frN. 2966: i Rap --" t Coloalr from N Ie hod Co DI [lagabhlaa 'Jqqeal ( YNlow) Aeld Fas SMdea. d J. Cun- Pat6 78:+25-29, 1887_ and BaLasr, Victor B. and PSD, U8in3 Ba~i loaotla'a I'a Iadinated Humaa Serooe Albumin, Ctln, Orthopadl 39:1''~-3i, T 00J:0529 The Cn_tlt•~t_ts. TLs.nk cnu, I Mr. SntterfieVd, do.~t.o.~u llure a \Fr. C.12TiRFfrtA. 1P.SItS COI: The C11.~1uv, Mr. Springe, Mr. SrxnN-asae. Dr. Buhler, sol I:nown to the committee for a I no scientifio evidence of the rel: hnve known that for a lon,g tim resolve in my own mind here i trvingto limit what cancer reall Someone said the other dac, a :md I tri=h I had cut it out of tha disease from 37 to 63. Would Dr. Brtv.an. Certain cancels, that occur at a much earlier : occur even later, The at'erage much earlier. The same is true .•oma, so that when tnlldng nbt ne has to be rather specifiSIr. SPnr.rata \ow let us cc -h1110 nle, that statement. He seemed t question of n-hen the cancere ac whicn I did not laow befote, a cancer occurs in men. Haa anyo Dr. Brasa. SVhy? Mr. Srr.weve. Yes. Dr. BcsneR. I do not think thinL- that there are plebably the occurlence of carcmoma, ~)11'. SYRrs-o6R Let me n51". ,fn tutes of Health, U.S. Public included women in this as 1re11 s Dr. BvB1,FJt. Ia some inst ineluded. Mr. SPxxrcu. This soparem is only one-fifth rou~hly or on+ o one-fourth the chance amot SBtraxls. The thrffit of m- 3Ir. SPetaoea Even if they di Dr. Btrar.zg. The thrust of tr. ply as follows. That if smoking rinn of cancer, then it would sel alift in the avefngo ap of cance age, instead of what has hnop/ tcould alsu seem to me that if t causative in catcinorm of the It eame as it does in men. Mr. Srarxcss You nsed anc out: "The disesse seems to appear nnd heavv smokers at aboat the e Notr m}tat is that age4
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: VNDERWDOD ET AL. grm a previous report• that the larger the moN , the larger the baby, and vice vena. spec (Tab iaan Th1s there mothers were grouped as to We o uimesror in whieh they smoked a 2). These data suggest that smoking tcimestar d^cremes the birth wcighL as not srmistically signifieant because M au 100/ e5 .«...n. were small numbers of patients who ap smok#d only in a single trimester, bownver, signJicaooe was esubRshed with smoking in all tri A the (Fig. Wi birth eantl birth deg=e gay rlse r esters. Iteo-tipped tigarene did nm influence ect of smoking oa birth weights )• maternal smoking, prematurity by eight and gestational age was tignifi- inereaied (Table 3). Prematurity by weight rose directly to a signifieant (p < O.OI ) with each smoking eale- prematurity by gestadoa age did not portionally (p > 0.05) among each smoking group; howeves, ia each smoking 8ra'I oaatq aoasi lated signil founl (Teb gestational prematurity was signifi- (p < 0.01) higher than the rate for oken. When prematurity was wen- with the fathers' smoking habits, no eant dl&rences (p > O.OS) were by birth weight or by gestational age e3). r+utu t Wtu n .rean wurwY u• Na. e- rR.e .r aew.liPM epah,la *. ..fios a1M r.iehh N hla.M Ye,e IM .uwuM9 .naen. Some major complications of pregnancy were evaluated in their relationship to ma- trraal smoking habits (Fg. 5). Both mild and severe preeciamptia dcemased propory donally to a sigaiBtant degree (p < 0.01) with the number of eigerettes smoked per day. Again, the maximum offeat was reached with moderate smoking. Of those with pre- edampsia, a significantly smaller proportion (p < 0.01) of smokers bad severe pre- eclampsia when compared with nonsmekers. Conversc7y, premature rupture of the mem- branes increased signlfleantly (p < 0.01) in each group with Ibe amount of matemal smoking. i.ass 7. Muw Lam Womxr ar 7aovane a Moraot{ S.a+apn Mwia fox oulY Seewd aJy Fblrsud SeN.d 7MN anry Ag Mothen (He.) 2/.a9a I7s 139 371 301) 20,006 Bhth weiahr (ya) fAr 1 3.10! 3.7t16 ]261 I,)77 3Jp 7.na 1 Peacwuae a Paew.+uea n~.am Aeeoamxi ro Patuvr.r. AaKOw f4ans Ctrarrt#sOrrdW' Ierous Naa /-m 11-l9 O.nJo Malws fnfaabunder75C0jam 3.7 7a 9A 11J laqeq 9edv 76 wda lJ 69 7.S 73 F:rhaa fahna andre bou tan. 6.11 a1 3.4 ii hdano smdsr se s1a Lf SA !6 9.6 4 eMYwn.N e..«.~... 0154233 . TLMN TIgI, 0305511
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1 A Study on the Swedish Twin Registry Friberg. JlD; Rune Cederldf. FhD: Torbjdrn Lundnsan, ifD: and Flans Otesen, J1D. Stockholm _ Among 709 mal , dilygotic. amoking disccrdanl twin pairn aarn I 1901 to 1925. 13 deaths oe. currad among no mokers or ta» exposed part- nan agalmt ]4 ag ng smakan or more expas.d to 24e correepca lag monolygotie pain ths fig- ures were 14 e ainsl 9. The exene morulity among TaN dixy otic smoxers .ras not afeoci- ated with any spa iie cause of dpth. Pour caaes of lung canear a ng malts occurred only in smoken. Aociden a and sutetdes seemed to be between smnkers nd nonsmokers. Only tims will show whether ire de found are stablb The date suggest however, that part ot tha greatv mortaL Ity In smokers is 2ua to smoking ps se but val to tacton associa ad with rnokirg, asvCeiatad with s oking, wpper[htg the hypoth. eees re3srding illarenoes in personality type eral diseases.L: smokers might groupo of twins rience..Even if between smokin was forrned. Th ing the registry with both memb I0,000 twin pai in the country up in the ye THE SVl'EDI 1{yq4nt. ForoUnsA 04 (Ur. Flibera/. Reprintrequestn aal DeprtmenL Imdtuts (Dn. x..un RAv, rnos herclineka rnsdtut submilted ler March 11, 1970. Fmn the depa PA - 000485 ortality in Smoking Discordant M{~nozygotic and Dizygotic Twins H Twin Registry was set 1939 to 1961. It contains of the same sex born with- twaen 1885 and 1925 and rs living when the registry main reason for establish- was to study mortality in ith diRering smoking expe- positive asaoeiatioa e.risls and early death from sev- exdea mortality among are g ven or w n pa ta orn in 1888 to ot necessarily be caused by 1900 The report includes mortality from the is ot en.tranmeatal hydsatk ad Natfcml Lstitms of A:blic a/e pderldlL ead tae .1e91. taynimtr FiosplcsL Kareiatska and Olaqnl, 5lnekholm. smoking alone. Smokers and nonsmokers are not comparable in all respects, partly because of possible differences in genetic characteri3tt4 releyBnL to the occnrrenlM of di:ease, and partly becnue of tttany other environmental esposure factors which may be correlated both with smoking and with the diseases The advantage of using twins has beer. discussed at a meeting arranged by the World Health Orgattization in Geneva in 1963:' by Cederloi in 1986,+ and at a meet- ing in San Juan. Puerto Rico in 1969.1 Since the establishment of the registry sev- eral atudies on smoking and health have been carried out - both an the Swedish reeistry and cnll'aborativeiy with the US Twin Registry of the National Research Council.'.4t4 The Swedish contribution.e in- clude quastionnaire studies on the entire roster as well as clinkak studies on subsam- ples. A questionnaire study was cenduc'red usine the US twins. The present report prosenb data on mar• tality. including caure of death, in senoking discordant monotygotic attd dizygotic twin pairs in the Swedish registry born in 1901 to 1925. Mortality data without oause of death i f t i i b forming of the registry until the fall of 1986. i f ~ General fntormatioo ~ the taln registry ~ is given in an eartier pubiration.r Smoldtta habits wert dMtermined from quesdonnOinr t1. pliae ~btainetl in l9tft. The subject& wew usked whelhrr thwy ware amokers nr nenemokent, t o Deparlnwm of Eavironroea~st lnsliM1~la. St04 ul staekbnln, Arch Enpinan Health-Vol 21, tJct 2970 f t ro020s(; TIFL 0305476 ' 1 11OHT abOLLt tlte ty1W . cigarette tonsua- more tt•an '.) C The mortalir. lisbed in the Lo: all nwins tegu:'r boatdc which arr nsidenta in th.: reduregices de of death r~es , The iniorrtcui:- matched a;a.s-. Cerlifuntea a[ i -tn this w y ti signed the dt= deceased h, in the n.une o; t^ HospitaL rttor prscfi5onera. 7 was Ihen e.ac made without : R'hen medic;,i the rauee of , certificates. Foe 95 death beth +.ere aza malion ~ v nh 14 cnacs enh' in tuv ~.s ~ t.vo latter rn "other cau+ea: The eniu:: ellaets ot <a. eomparint de=: nonsrmkes ic respeGRn9(.'- C smokers -he The eapoa presented in 19%. Ttfero L diacrxicand In order t, the comt>zris' a "less ex,d•s nonmsuken : snwken. Th. opera6anal:~ Leu Er L Ggaretta+ (mm: 144 69 N1Z: women. 9 43 . IZ) 2 Caerens <30/d: (men: 1r 6m7:
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agm. I I • .- 4 I MONTHLY VITAL STATISTICS REPORT in L972. and represented decrease of 9.8 percent from the estimated rate in 1972- Bronchitis, mphysama, andasthma-_In 1973 the estimated de th ra[e [oz Bronchi[is, emphysema, and asthma was 4.4 per 10Q000 population, an fn- crease of 4.3 per ent from the estimated rate of 13.8 Death Ratas by }19e. Color, and Sex Curing 1973 all the age-specific death rates per 100,000 populati n decreaeed from the t972 rates except for the ge groups 1-4 years, 5-14 years, 15-24 years, 75 64 years, and 85 years and over (table D;, The i rgest declines occurred in the age groups 35-44 y ars (down 4.0 percent) and 65-74 years (down 3-3 ercent), Wh:te mote ,-In 1973 the aga groups under 1 year, 35-44 yea s, 45-54 years, 55-64 years, and 65-74 years ha the lowest estimated age-specific death rates ever ecorded for white males in the United States. The age roup under 1 year had an estimated death rate of 17. per 1,000 population, a 1-7-percent decrease from t e estimated 1972 rate (table 5). .4R ofher les,--In 1973 the age group 65-74 years had the owest estimated age-specific death rare ever record for the category "allathermalesl" The age group nder l year had a death rate of 33.0 per 1,000 popula ion, an increase of 8.2 percent when =ompared with he estimated rate for 1972 (30.5). Table U. pEA'('H RATES 8Y AGE: tNl'1'ED STATES, 1972 AND 1973 ~dnaM on n 10•pen:dnt sample of deaths. Rates pQ 100,dn0 peputa- tian in spenined gronp3 Age 1973 1972 PerGenC differ- ence All agsst - 942.1 942.2 -0.0 Under 1 year- --- 1,796.0 1,195.4 0,0 1-4 years---- -- 79.9 79-4 0.6 5-14 vears--- --- 41.4 40-7 1.7 15-24 years-- --- 130,6 129.0 1-2 25-34 years- --- 152.7 156.9 -2.7 35-44 yeers-- --- 289.0 301-1 1..0 45-54 yeara-- -- 698,6 714,2 -2,2 55-64 years- --- 1,607.0 1,612,L -0,3 65-74 years- - 3,434.7 3,551,7 -3,3 75-8G years- --- 7,976.7 7,901,3 1,0 85+ years--- - 17,446.6 16,222-6 7.5 groups. ' Ftgurea for age not stated included in "All agee" e not dlatributed smottg age Whrte females,-In 1973 me age groups ur:der I year and 65-74 years had the lowest estimated age• specific death rates ever recorded for whfce females in the United Staces, The age group under 1 year hs.d an estimated death rate of 13.1 per 1,000 popular.an, a reduction of 9,4 percent from che estimated race for 1972 (13.7). Alt other Jemales.-tn 1973 the age groups 15-24 years, 25-34 years, 45-54 years, and 55-64 years Sad the lowest estimated age-specific death rates ever recorded for the catngory "all other females," The age group under 1 year had a death rare ot 29,4 per 1,000 population, an increase of 13.1 percent when compared with the estimated rate for 1972 (26.0). Maternal ond Infant Mortahty In 1973 the deaths of an estimated 470 women were assigned to Complications of pregnancy, child- birth, and the puerperium. The provisional maternal mortality rate was 15.0 per 100,C00 live births, This rate is che equivalent of one maternal death for every 6,683 live births. The maternal mortality rates per 100,000 live births for 1950 and the last 14 years are as follows: 1973 (est.)------- - 15.0 1965------------ 3L6 1972 (est.)------- - 24,0 1964------------ 7?.3 1971 ------------- 18.8 1963------------ 35.8 1970 ------------- 21.5 1962------------ 35.2 1969------------- 22.2 1961------------ 36.9 1968------------- 24.5 1960------------ 37.1 1967 ------------- 28.0 t950------------ 83.3 1966------------- 29.1 In 1973 there were approximately 55,300 infant deaths resulting in an estimated infant mortaliry rate of 17.6 per 1,000 live births. This was the lowest annuai rate ever recorded In the United States and represents a decrease of 4.9 percentfrom the esti- mated rate of 18.5 tn 1972. The infant mortality rate was a record low for every month in 1973 except February. BOth the neonatal (under 28 days) and the postneonatal (28 days to ll months) monality rates declined in 1973 with the neonatal rate showing a proportionately greater decline than the posmeonaral rate. The infant mortality rate increased far two causes of death during 1973 when compared with 1972-Certatn gastrointestinal diseases increased 50.0 percent and Birth injuries increased 20.0 per- cetu, TIFL 0305501 I
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284 Ycrulhol y 8• .1cDon.~l , R. L., and L.nfnrd, C. F.: Obit<t. CncroL 26: 470, 1963. 9. Abernathy J. R., Crccn6uy, 3. G., tt'clls, JL 0., et L: Arn. 1• Publie IIctlt/r 56: 630, 1966. 10. Rcinke, } A., ar.d flnxlcrren, \Lf Arclt. Swiron. f.nhh 12: 6ri0, 1066. 11. Rarcnholt IL. T., Lninski, \(. 1., lcI(ut, D. J., m, 1'alrnn;a, }t.: .1x. y Ons'ar. Gvsracni.. 96: 71i7, 1966. 12. Xfser, S., Rev. ObneL CineeoL Veno. 27: 593, (907. 17. Terris, N[, and Celd, E.: Ax. J. Oueres. Cvs[cuL. 103; 358, 1969. 14. Dunehcr, . R.: Ax. 7. Ossrn•. GvaaeoL. 103, 942, 1869. 15, Slnlcalry, lL, SfurGhy, J, and Slartia, F.: Ax. J. OsTr.T. GC.+'iCCL. 106: 703, 1976, 16:. Savel, L., d Rotlr, E.: Obrtet Cynccel. 20: 313, 1962 I7v O'L+n4 . hf.: ObRCt• Gynr:coL 22: 181, 1963. )& U,tderwb. , F., Hcrler, L. L., Lalnta, T., Jr, and rcSB R. V.: Asr. J. Osrrn. GYYLGO4 91:2i0, 1965• 19. Petonan, N. F., \Larfey P.• N., and Xal- emider, I . P•: Obxet• Glnecel. 20: 778, 1965. 20. Doaein;, 1. C., ond Chapman, lV. E.: CaGL 7ded. 101: 187, 1966. 21. Robimm~ P.: PIacnfuah69: $7, 1045. 22. Jaunan, .: Acta O4ncL CyacceL 3and. 45: 279, 1 66. . I...+n ti Isrx 'M. J, UbnrL UrurY. 23. 7•une, C. R.: IIn ~fcd. 7- 2: 673, 1959, 24. Pauier, T. \(., Da'ir, C. If., Gokhtcie, H., nnd Coldbcrg, f. D.: Au J. Ousrsr. G ea LeroL. 61: 9811, 196 t. 25. Zabri.kic, J• F.: Ommt CynccoL 21: •105, 1063. 26. Rusvll, C. S., T.ylor, R., m,d d(add'uvn, R. V,: J, Oh,rrn Cyarcol. Itr. Ccmmawr. 73: 712, 1966. 27. Cmnclock, G. 1V., ar.d Londin, F. E.: Av. J. Oss•cen Cvaenut. 99e 708, 1967, 28. 5(u.~hv, R., .a.,A Xnass4 1. F.: Aso 1. Ossrcm. Gvaiz:Or. I01: 61f, 1969. 29. Xu6snd<r, S., ^aA Ks17en, 0.: :4u Obnret. Gynecnl. Sawi. .i0: 83, 1971. 3Q Underr.mod, 1'. P., f:esler, K. F., O'Lanq I• .lf., cr a/.: Obrtet CyneeaL 20: 1, 1967. 91. Ranu:al[ia, P.: Aem Pxd'un• Seand. 1911 1, 1969. rSopPl•) 32. Sutkr, N. R., and Albernun, E. D., editcrs: Perinarcl \fnnnlity, Edinburgh, 1909, P. & $ Gvingstanq Ltd. 33. Ycrudtalmyy Js Ard J. Epklemiol 93: 443, 1971. 31, Spapirv, 5., Schlcein;ee, E. R., nnd ~ed,itq A E. L., Ja: LJanq Ye.imed, ?Gtera>I and CbiWlwod )[urtality ia the Unilcd Statea, Gabrid9e, 1969, f[.nvd Univenity Press, rv 51. 35. TSyiar, 11r. F.: In Fnm, F. Clarkq edimr: TLIrd [at. C~ faaLnce on Cen3cnim[ ]lalfurrantions, Atnrtsnbm, (970, E-.ee:pta Jfdica Fcundatlea T faa hu rnr or, pr, for ui [ic j.N, rt: TIMN 254631 TIFL 0305523
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. VNDERWOOD ET AL. a ......ee TIMN 0154237 TIFL 0305515 10.0 we• 1. M. Snnx fetal elken ne esrmal C' arare rmaWng. OMur Cruec J7att• 19 . L, md Rorn, L ERecu of fnwking h prernancY: A rontiauin` ntrppeetiee rudy. O nrl C1wee 20:313, 19f1 'li aex, F. U. Clpreue mw9tna io prey e7, NM yare I MN I1:1945• 1941. 11. 91[tTnN, W: J. A prellmNary npat aa er.ntn unekint snd ms ieeidencs ef pre• AooW~~~irtrtuTrlry. Ann J 06rree OS•ere 7)a12. 1937. It 9 .c, L W.• and Wa.uR R. F. EOee1 ef aruM rmeefnt: durinp prepnanqq upon feral he nte. Anmer I Obrar Gynre 29:77, 19J5. 17. awr; C H. Lo>AS.rr. C F. Fenm:c• F. S„ f.eue. A- 3_ and Eusraow. Af. hldividual and hospital mmes. s. Any publiettiom which may result from Ibis research will maintaia woaymity tetria and gyneeology fo hospitals with approved ohstnde.gyaeeelorie reddea- digent. Latey this year a qnesuonmire will bc maikd to all cha'vmsa ot depanmeats of don'to all pademt, but with partkalar emphas3t oa ssrvtees for tbe medically a8eeting the availability of eontraxplitte advice, sterifiaQon, and thenpemic elud'olg the teobiag of ths rhythm mnhod. The study wf11 also be eoneerned with is study is one of a series designed so explore the tfa3ning awilable m members the health professioas eiuh regard to assisunee with methods of family plaoniag• meriean Public Health Acsodadoo (Joww W. Ettoi. M.D.), is being plao0ed. Ilege o/ Obxtetrician. and Cyneeologists (J. Rosaxr W9uaotr, M.D.) and the Altentbna in reproductive funeuotr ef wline ranS nsoehud vl:h da9y e+Msun b niroliRG I P/nrnposl Eap FArr f7:1. 194& Ii. Unernweep, P. s., Nama. L L• Lrnrri. T., WA Ot/no. 1L V. The nduiaesElp of uealdne to the earenme of preran9. Amer I Odraa G7ne 9137t1. 1963. 17. Yaauanaary, L MotherY dpr.tn arnokles ae0 ainival of iafaet. Anxr l Oban Gynrc Ld:50.f. 19" 11. Yeturuuw. I. `Smetieg Ha6W Of F'Nher Weltht pt 1ndn.' rn rubnern end VTAera~ Spr(n9field, Ilf.. 19Q, p. 216. 19. Luurru. I. R. EAep of eipanW amvtinp dutie f%Lt possaafty. Obrm Gyna 1f:e03, Study of Famtly-Plannuzg Training and Services in Hospitals with 0bstetric-Gynecologfc Residency Programs A study of hospital teuhin;.programs, policies, and practices in the areas of nuacepdon, sterilization, and therapeutie aborUon, cosponsored by the Ameekaa
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pAAENTAL SMOKING of inembranes eoald account in part for the irlrreasad prcmaludty. AIMMeeT A prospeeti9e statisticaf sntdy of 48,505 feGe on lha rnee. FareMlr Med 11:133. 3 4 ~ 1964. b yy~ CRR~g M 3. &mo:u.0. 1. M., ScnWU+a. 1. V» and PA1nes, A. R. EIhoM at nleeline and piguetle enaRe aa OreJ/aant (amate albino na and their oR/ptn9. I Lab GMe Arrd 31:701, 1939.40 M d «a r; . 4. Puau~ T. h1.. Devs, G. H. OunsrMM. N» and Oetneur, I. D. C6.retM rmpWa6 ud s L 4 pregnancks was wrriad out to evoluate thc eQeeu of parental smukinr on prognaacy. Allhough the infantt were smallcr and the aeidetlce oI prematutity waa gr¢ater, oo ad- vetse effeat of maternal smokingduring preg. I h 2 1 I t I t i ~r. aRnry was sho.rn in terms of perloatal teor- taity. The incidence of pteecL]mpsia Was decreased with tRatarna{ smoking; however, 3 other, more freqaen4 complications of preg- ~ 4 lunty were increased. Neither smokin; by ~ a ~g~mlk R- 16then nor the use of 6ues-6ppcd dYarcttea Rfeated the outaome of pregnaney. : ~ 6 d '°..nr., R A U. S. Naw/ Harpile. NeaionalNal•alArrdlralCeater i A ~ laheed.. INA. ?0a.11 RrtrrMe,{{ Y ~ ^ . '1 R $ 1. Aneoc, A. O. Jnat. O. D. Laue, W. E., tame. W. A. wd Ca.v.ativ, D. A. Pra aG i ~nwG ~'r.y^ a .J e malurity: A mere maim spproach to iduu& atlen. ObruJ Gylne II:761, 196J. 2 Rsatwl.an, P. Smokirg ro Pre'nalsy IC Ef• >, aa.le. M.1 M~.w,rleer wwR w.~ t~1'i.. Oal Grxrc d!916. 1 61n Mudy. AMMr l 1. HruwN, J. 61.. IalMSalr. It 1.. Tou.fu. W. E. aM lawn. E. H. Some laclen a6• fecYn9 Itr fetal heen nlp. Aewr I Obrrce Oleee 6J:toss, 1961. L Itnwar, A., Rluema W. Z. W Hnrmv. F. E Cigarette rmoklne in Pleenancy. taacn J:TIt.1967. 7. LnwG O. R. EfeM ef Illottlefs rmokine ha6iU en Litth ,aeleht of ttMfr chitdren tNr ARl! 3:673.19l9. R M.chfuwM, E. Auult, 6t. aad Swea, 8 l. lniant .ei9ht and 9ananl tasaktna Mbib. Unp.llished dul. 9. MeReewM, T and Receea. R_ O. The Ia - Ruenm of body *vi9ht en tapmdeclhe (uoa• rian te wuxa. I Eedacr 11:410, 357. T TID'IN 0154236 TIFL 0305514 --
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_..... ~, . w,.w,. s, vr_moaca, rtemPn~, acnauer, aoa Imm,m::\sntin<and artermsclermo aher cholesteroi fe din_q; thus increased lipolrric atuvire smoking" in coronary hart disease. In this conneetion, ~ does nor seem to csdude sdecosis. The inaeaee in a paper by HFSS and FROSr (49) may be of some im- tise amsin• of li rotein tipase mar be a consequence portanca These authora demotsstated alterations in of a disturbed m bolism of the eortfc wall which aortic intima with a new electron microscopic techniq,e . seerm to be the e during sclerosation and which in rabbits after relatively shnrt exposure ro robacco could be shown several iaresdgadons on enzymes smoke And condrmed aith these findings eazlier rnuhs : of the sclerotic resfd (for xeferences see Pt.Srr (48)). of SHSU.auoro (50). It seems possible, that a prolonged A very important nding in the present investigation is nieotiae action ma,r produce aicification in tussues, ' the sigaiGcaadp el eaced aldum content of the aorta of the nirncine-c red attimals, with no inaesx in the calcium concent on of the serum. Further int•estigo- tiom eill be nee d to eonfirm and to eraluare the mechanism of th' finding; Ho1ee5•er, it seetm that alteradons in zrt rial tissues are biochemiolly de- monsttable before angee an be shown histologipEly and that the estima 'on of the cslc,em content is a useful method For the esi ation of the degree of ca)d£iadon. Ccne/aJivn be~laea o4iea and rurenur}• Jxert dinnr plp some eaidence for a possible participation of ni otine in an earlier manifesration of coronarc heart dis~sse in smokers. But considering the amount of nicotine possible ditTerences our experimental likely dut nicotin admiristered in this e<periment And in resorption between amokers and onditions, it seetns mus not vety alone represents the "risk factor altered by other conscituencs at tobaceo smoke> there- fore, further substances shauld be sought in tobacco smoL•e, which mat be connected with this problem- In . this canneeriott, «sults of 3stntT and coworkers (il) . should be mentioned, who found havc arcctiscleroclc : iltendons in the coronur arteries of rabbits, esposed to cholesterol feeding and an elevated concenrration of -, carbon monoxide in the cespintioa air. .' With regard to the tosids,r of chronic nimtine ad.airi- i stntion, no indication of damage to organ s}tttems has : beenfound;espeeiallynotescorthyistheabsenceofpatho- ` logical values for serum enzymes. TJewoRr (52) found an increased value of aspartate ennsamimu Xe did ~ not observe a change in aspartate mnsamioaseacti~7n, ; ahiehcorrelates.t-iththeabsenceoFhistolaginlnadings. ' .{ Btanr ftcm nc. "nisaenseh.hlkhe Foes<Isung»selk im Vm i band dee Cipnenindurtrie, Hambueg•' is gntduLLy acknovt. ~ ed8ed. Refernncea - - 1. Smoking and H alrh. Reperr of the Adriscfe Commimrr ro the Surgeen Gen 1 oi rhe Publia Halch Semm Public Helsh Senice Publi cion No 1103, G'ashingtun DC (Tan Rcpocs) (196a).-2. he Hevlrh Conseo•uenees of Smok- iag. A Pubife Halrh <rsiee Re.iw-. C.S. Depanmenr of Halrh. Eduocion ard Wetfare lC'ashingron DC (196%). -3. Doru, J.7., T. R. D..ascR, ti<. B. 'n..u•. S. H. Fc.cst and H. A.J. Amer. Stcd. 1r. 790, 686 (1964). -4. OsaaanrruR, W, .lted. l\ eir /968, 2478. - 5. .{cssa.sex, 0.. E. Hnsmm.n And L GeR- xc,c¢, \- En8lard . Mcd. 2:), -:3 (1^•65). - 6. Kunar.t, T. C and D• T. v'err L.{ppl. Phxsiol., lC'ash. 19,40 (1964).- 7. Scsrwot, E., \. A T.tta, P. Wc%TSa and L 7acsu, Yrrb. Dech. Ge.. inn. Nrd. Tr, -01 (1963). - e. Vasos, A. S., Beis. J. Pharnucot. 24, 256 966).-9. Ksassta.cu,.{„ 5. Buurand J. Jnaai; J. Am.er. d. Au. 19), 1093 (1966). -I0. CseetrR.t- Ln,,osaca, A„ M. oRSU ar.d N. Kaos.y Ann. L-ni<. Stariae Curie•Sklodoetka Q( d.) 14. 181 (1939). - 11. Txlc.v, C. H., Ann. \. Y. {~(, k 90 239r1960).-12 H.ss, G. 3L, l7. LuaeR- swus And A. H , CucrJanen 3a, Supg1.3, p. 14 (,lbstnct) (1966).-11Gan r,Y.G•,G.,lxeanw, J.Leuarcn. B. J.a cororarsdJ.•LBsu .,.J._{chawdrxAes.3,291(1963).-14. wc~~ D.G. and G. Beea•on, J..{ctr. Pharmacrnc.{ss• Se ed.31, 338 (t938). I3• Gans.uv, J. W.. F. T. LmneRN, 8• Sr*raosna, O. F, sr-uta, F, Gr-sarsR and A. T..usu., Geriamb, NbaeeaPelt 10, 349 (1935)• - 16. Kna.•e.2., 3L, H.Ousa, d• Kass, F. ros.za end J. Baases, Ianur, Loodon (1959/3, 491 - 17. oonuSrevRar, 6, Brit. \led. J. t961/f, 379. - 18. K/aaR "- B., L K. O%muae and T. R. Dw.•smr., Schcec. mrd R'xJr 95, 18 (1965). - 19. Kesusn.nr, A., S. Braur, E R. Dte rtn sad L J. Fsrx;vne, Cir<ulaL Res. 9. 63t (1961). - 20. Ss ts, A. And 1. H. Paoa, J..1mer. Sfed Aa• r9S. 138 (1963} - 2 . He.ntv, 5., in: G. Schenltr u. R. Sen- mald, Epideesiotegie der Koromegeisfkrkeankungea Padse. phlsiologischr ur.d kt -{apekra dq FearoBu•tcltsela, Thirme, Srunprc. (1966). - 2 t:R.tuaR. K., S. Pncu~ And L. IX'eRRo, Ciraslanon )i, 388 (1 66). - 23. A. And AL A.JF. s.eurz, Hrie. Ved J. 1963(1, 830. - 24. ENnaeua H., Cireula- (0020493• TTFL 0305391 tin,n P, SuppL 3, p. 10 (Absreaee) (1966).-29. Dcseessse, n. G.. }, Biochem.J.B.t,t(1963).--26.nsotreR,B.,1ml.hb,11,1t / r (1963). - 27. Geurn, P., C:in-ehim..{en (.{tnsreniam) 6,'I9 1 J (1961). - 23. D•, Clin. chim. A<u (Amuudam) i, 637 (t960). - 29. Cacuaos. C. and J. CarRaN.Ar, Preare med., Paris _ 96. IT13 (t937).-30. ZiW.vax, S., and D. EsdweeM, L7uer• auchungund8rsaimmunSderLipeideimBlue,Springer(19651.- i 31. Scstses;, H. And J-H. GatuRSrs..v, Z. amt.e. Chem. t01. ~ 1412 (1960). - 32 Setatnie.assv, H., And f: Gu~eu, Z. `,. . . anal.t Chera 2)7,1 (1968),-33. IL.aun, A.. J. CIin.lnvne I{ 'i t31 (t9S7). - 34. n Ros[isfsu, E. And J. S. L6 Dce, Proe Sx. I eep. BIoL Jkd. 9), 569 (1936). -33. Hot:sR, H., J. H.kv And I 5. Sen.aosR, Bioenem. L J26, 451 (1957). - 36. \nc~ 'a., i F. K'rs.ue and F. H. Scxsrror, KI(a 0 sehe 42. 447 (196a). -; 37. Soaoun, M., J. b(nl. Cbcmmn• 127, 399 (1938). -38. Frsre- ~ u.s-v, n'. H.. J. biol. Chem'srry 100, 69 (I953),.-39. Busar• O. 1., ; 0. H. Ltmnr vsd M. J. BRocC J. bioL Clanisoy 164,321 (19a6). i 10. 1VROrtemsK; E- and 5. J. La Den; Proe SoG eap. Biol• >ted 1 90,210 (1953). - 41. FutRU, P. V. and A. B. H.ast. Amer• J. Oin• ~ Path.28,9)8,689(1937.-425estvtreRtar,CG.srMEHU%s • sox, in: l).S• .. Eccen. Tobetm aialeids and mlated compoundr, j Pergamaet Prm, ORfmd (1965). - U. Semas•a~* H., in: ' H. Sertus'oJnt; \ikoein, Phanerkelogia und Toaikeb8ie / desTabakauehee, ]hfene Snrttgset (1968).-M. Sessrnaaun, ( )F. And V. Ia.ssoseo, uapub)ished. - 43. Ct.rnesr.ur, H. UL f and D. W. FRtnv, J• Animal Scf• 24, 41 (1963). - 46. Gco- t s)nt ..sCoi. 5., J. Pbumsepl. Erprn Thevp., Balsti,nom rss, I: `r (1968). -47. ZssartIN-M T., Z Lo)ss, 0. MRStw.y ia: Sn..msR ~ and BocR~z, Atheeosdemris and iss origist, Aaderefe Press. \es• ! York, Londen (t963). - 4L Pacn, D., Med. Klin. 64. 126t ( (1969). - 49. Hess, H. and H. Faoer, Faraehc 1fed. 86, 841 i (1968). - 50. StmGSrme, Z. Asian med. J. 3. 479 (1960). - i 51..{srnue, P_ K. K)rs.esw And J. rP.t~Rrr. J• AchmweMesis i Rea. l, 343 (1967). - $2 T)wavnrrs, 4i'. W., Vleebo.a 4ch. ; parn. ,{ML Jid, 29 (1969) fr. Pmtt nr. H. Sebie.elb<in, 8db Murxhn ls. Nnsabeuneee 20 I Z kBn. Chmr. n klin. Bieeham 1 8. Jahty 1978/ Heft 3 i
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----`` RANTAF;P.L 0, ?aula, Dep.2rtm.=nt of Pediatrics, University o? 4alu, Finland, Group'at risk in 1oa-birth-weight intants and parinatal nortaiity," Acta ediatrica Scandineviea Supp].cment 193, published 1969 bv Rimqvist & Mik cll, Stockholn, S~edcn (71 pages). ' ' Tne object of the study ~!as to pic'i out thesc mothers tatose prcQnnZ,;1 k:very discriai:Lnt ran a ri k of perlnata]l morta.lity or loa birth maighta function analysis involved two groups,one consisti.ng of 1000 conCrol casea (taken b rand;.m sa;apl.ing from sox^_ 10,000 cases) oinile tho ochreprcented a risk r ~ , as folla:•s: . . Anat lysis Aisk groUZ''' No. of cases A Birth weight less then 2500 g, all cases 1~99 9 Birth wei;ht less than 2500 g, deaths o11.y 164 . , C Birth weight 2500 g or more, deaths only L'9 The 15 variables with the highest weighting (of 43 used) in discrir- i~nt f nction ana vsis A are liate3 in ordar of decreasing power of discr_m- ination (smoking is tenth). The 20 variables mith the highest i~ref.Ehting in ane si B_ are liatod in ord.er o.* importance; smoking is 16th. The 15 varL sbles w th the highest weighting in ana sis Q are listed in descending order of disc iminant power; "non-smaxer" is 15th. . "Mother'a smokin . The distribution of all cases by this variaL•.te is pres nteln le 2f sce below).... As can be soen...mortaTity rates ~rerc lower ' both weighs ~,roups if the nother had smoked than if sh= had not. Sa the bir h weight group of 2500 g or more the 3ifferonde was statistically signifi ant. The Lo'.+ birth weight rate arw'ng smokers vas, however, so vuch higher hat the tq}&.L.gartnlity rates we-re the same for smokers and non-srokors. In the iseri~uinant functidifZ'S{IysB' , mo+ ne er. ed o e associa e w. the ris gror-n {A or BJ...and with the control group in analysis C. 21.5 per of the eent of all the mothers of the series sno:ed.... . "Of all mothers of 1ow-birth-weigtt babies, 32.1 per cent mere sao.cr:, others of lovrbirth-•weight infants whose baby died during the perinetal period 8.4 per oent smoked; of all mothers giving birth to i.n£ants weiQhirg 2$00 g r more, 27..0 per cent aere smozcrs; and of the mothers of this bir',;:1 veight 19ss babies witiose baby died during the perinatal period 12.'( per ceot smoked. ' TIMN 254784 TIFL 0305507
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I i UNDCRWOOD ET AL. Teett L Q..ayne.vm.v oe O~newn w R.ee wm f..oarrvu H.artr CWRms pn Gi• Iar4w N.w f-70 fI-i0 OinJO Toul No. 2t 74f 10.079 U,3Tt ft7 t'+e<,wa (q,) x: ns s1.1 954 Other (R) ti.g 17.1 69 u T.ut i Maniae os Durveav .wo l.f.tnwa f,urd6 il.am . [tp..oa p" d.v awaMA.r /Va.r I-b ILfO O.erJO Tntal Na. 21.349 104171 t7,273 $17 vednd ma 9" 97.3 e7,o 97.1 Cssarsa asden (%s) 7.7 2.7 sA 23 Table 6'shows the sex ratio as influenced by mothen' aad (athers' smoking habits. This table was compiled from similar Navy data cards for 1964.• It adequately shows that the sex ratio it independent of maternal and/or paternal smoking habits saeusuor. Infants born to mothers who smoked weighed kas and the incidenee of prematuo- ity was greater. The clinical importance ot these findings was minimited ainee there was ao iaaease in parinatai monality. The ab• senee ofiacreased perbtatal mortality related m snaternal smoking was sorprisint beause our data demonstrated a definite decrease in birth weight and increase in prematurity in these iafanta. The decreased perinatal mor- tality In the premature Wants born to emok- ing mothers can be eaptained by a lower mean birth weight but greator gcstatlowi mamdty. This was consutent with the Bnd• ings of Asetil es ai. of a bwer pminatal mmtality for premamre infants with longer Qeatadenal a{es. ITd•decroase in birth wei&ht of lntants baas to smeking mothers vas present throbCbout the third trimater, confirming I By R Bueeeer ae dn slamrd &6eel of pW/k slah4 the findmys of Frazier et af. Our data suggest that smoking in any trimester decrcua birth weight Paternal smokfttg did not deercuo birth weight at any gestadonat age and was not assoeiated with premature deliceries. The surprising and significont decrease of preeclampsls among the smaken was with- out explanation. The lnddcncc of prceolanp- sGL both mild and severe, decreased directly with the aowuni the snothen smnked. Fur- tbemWte, it preeelampsia was pcaent, a significaatly (p < 0.01) higher percentase of the nonsmokers developed the sevete tarm, lendinr credence to the theory of a possible protective e8tet of snrokin; on toxemia. A similar decreased Incidence of preedampsia uith smokieS was supgested in the data of fTnderwood et d. The eBect of smoking on preeclampsla will be further evaluated in sesttlt of factors other than, but associated with, smoking that may have io- ftumeed this decreased inddence of pre. eelampsis. Although the incidence of pya lonephritis, abruptio plaeeuue, and plaeema previa wa statistically significantly fnvemued, the elinieat unpatance would seem small bc. eartse in aach easo this fserease was Iess than 166. Premature supture of the mambranes in the smoking mothers was likewise without eaeplanadon. This earlier apontancous rupture 6 eY„iiM, N errWe TIMN 0154235 TIFL 0305513
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498 70SEPH D. .NAT.IRAZZO AND GEORGE SASLOW and s oking in any of the three groups. Thus, studying a total of 294 in ividuals of widely varying ages a d a considerable range in socioec nomic status yielded the finding at smoking seems to be un- related to this measure of socioeco- nomic tatus. However, a study by McArt ur et al. (1958), described below, indicates that, for Harvard underg aduates, "nonsmokers tend to be ower-middle class in origin, upwardly mobile, earnest young men . . . " (p. 274). These authors (p. 269 cite a survey published in Englan in 1948 which "suggested that onsmoking was commoner among men of the English middle class w ile heavy smoking was com- moner ong English working-class men." These results appear to con- flict wi h our own findings. Further- more, ur own findings with the Hollin head measure of socioeco- nomic evel seem to conflict with the finding by Sackrin and Conover of a relatio ship between earned annual incom and smoking. However, when i is remembered that educa- tion a d occupation (the Hollings- head easure) do not correlate highly ith annual income, and that in all robability, neither correlates highly with the McA.rthur et al. meas e, it is apparent that better indice of socioeconomic status are requir or, in their absence, a study emplo ing the available indices with the sa e subjects might shed some light o these inconsistencies. Edu and cigarette smoking. The ost direct results bearing on this elationship were given by Lilienf ld (1959, p. 277). His study showe that adult smokers and non- smok do not differ significantly in final umber of years of schooling compl ted. There were as many smokers as nonsmokers who had had no schooling, or who had attended college, etc. For people still in school, since age and number of years of school com- pleted are obviously correlated up to about age 25, it can be concluded that up through high school, college, and professional school there is an increase in the percentage of smokers as grade level of students still in school increases. A study of 6,374 college students in 11 Texas colleges (aged 15-39) by ICirchoff and Rigdon (1954, p. 296) showed just such an increase of 30% to 63% during the four college years. A study by Horn, Courts, Taylor, and Solomon (1959), on the smoking habits of the 22,000 high school students in Portland, Oregon, extends these observations backward into the high school years. For boys, smoking increased from 14.5% of the total in the freshman year to 35.4% in the senior year. The comparable increase for girls was from 4.6% in the freshman year to 26.2% in the senior year. Raven (1957) provides some anecdotal ob- servations on the smoking habits of English schoolboys., A study made of a group of college students at Antioch by J. R. Earp (1936) showed that of 177 students who smoked, 57% failed to graduate; of 176 nonsmokers 31.8% failed to graduate. Vallance (1940-45, p. 139) correctly points out that this finding is merely a correlation and reveals nothing about smoking being the cause of college failure; individuals who earn poor grades might be the ones who take up smoking. A study of smokers and non- smokers as related to achievement and various personal characteristics made by R. M. Lynn (1948) showed that adolescent boys who do not TIFL 0305542 Soci Inde M A IQ: n F An I Ps• Sy Cu, Lic a r sn- w< fa. tr c: re: sic sr. sr a: a r. s1 sc
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t - ! dfOR7ALfTy IN SSfORING DISCORDANT TIVI\'S-FR[BERC ET AL 509 f ~nt -Lin5 ind nonsmokers ,l respects, partly rJnces in genetic !ha oCcurrence of - .• of mony other ::on w•hich mav -nuking and wit.h .e t.cins has been .•-Mnged by the r in Cer.eva in ' and at a meet- Rico Rico in 1'59.' the registry sec_' 111d health have ..'t the S,.edish : ~• with the CS .t:onal Reeearch .oatributions In• ; on the entire riles an subsam- : was conducted '-s data.on mor- _.~ih, En smol:ing 9 di.rygOtie tnin horn in 1901 to ''. cause of death' 'm in 1886 to ••tntity from the : ii;e fafl of 1968. :hc nan reyrtry .-ntfom~ Smo:dng •s~erlionnalh te- wert aaked "r nunsmocen, about e type of mtoking. and .vhetMr their rigaret e conswnption was 1 to 10, 10 ta ?0, or more 20 dgarettW The mortality among the twins was sstab. tished a the following way. Liata enumerating all hwi regfstered were sent to the county boarde hfch are obliged to keep reeerds of the reside in their respecdve counties. This pro- redure 'ves time and place of death. The caux of dea uas obtained in the folfowing way. The i ormation from the county oeces was ma against the Centrat Registry cf Death CertiRc tea at the Central Bureau of Sralisties. ]n t' way the name of the physician that . aigned e death certificate was obtained. lf the deoe twin had been treated at a hospital the n e of the hospital Lould be deterroined Ho.pi records. inforamtion from general practid rnn. and other pertinent information was th examined. The 8nal evaluation was toade e thout any knowledge of smoking status. lPhen 'cal information was nat a.ailable, the n w of death va obtained from death cerd tea For deaths hospital reeorda or sutopsies or both w re available. and for Me deaths infor- madon was obtained frarn local physieians. In 14 only death oertifl.uta were uesd and in two ses thete was no information. These two la ter rvses have been included under "olher nuseal" The evaluation of hvpothesea about the eGects f smokin; has been carried out by compar ng death data for cigarette smeken and r.onsmu en in dia)'gotic and monosygotfc pafrs- respecti 01, Cigarette arnokera include cigarette smoke wha aLo smoke ciga» ur pipn or both. Thr sfwsure to tobacco in these grvups ia prasent in Table 1 for pafn born in 1901 to 1925. T em is practically no dilfewnt, tvtween diryge " nnd menaaygotic pain. In o er to increase the number at risk in the com riaon u.ing smoking discordant pain. a'lw spa.ed" group has been added to the nonvpa en and a"ttwre exposed' group to the smok. These two added groups have been spemti nally de5oed . Expoted More Exposed 1. CGga tes only, Cigarttea only. <1 /day 10 to 20 per day ; (men 144 DZ pdn, aqrNte, - 69 f2: 10 to 20 pa day wo : 95 DZ, end cigars or 49 IZ) pipe or both 2 Ci neeonly. Cigaretrsaonfy. <1 /day >20/day: (m IBDZ, vigarettes. G Z; >20/day and women: t DZ, cignn or 0 NIZ) pipe ortroth 3. Cigarettes only. Cigarettes only, 10 to 20 per day > 20/day;' (men: 25 DZ pain, ciganttef, 10 L1Z pain: 120/day and .vomen; I DZ pair. cigara or 51vtZ pain) ptpe or both In all comparisons when not otherwise speci• fied. amokers include former smokers. The age distribution for disyaotic and mono- sygotk twie pain born in 1901 to 1925 iis shown In Table 2. For the meu only minor diHerenteu between dizygofic and monoxygctic pain exist. A somewhat higher proportion of the dirygotic than of the monorygot(c women was classified into tbe otdest age group in the lets expoeed-more exposed comparison but not in the smoker•nonsawkor compatison. Results Table 3 and 4 show the number of deaths among smoking discordant dizygotic and monozygotic pairs born in 1901 to 1925 for -men and women, respectively. It is apparent in the male dizygotJc paits that ehe smokers have a higher mortality thazt the nonsmok- ers. This excees mortality is statisticalfy s'.g- nificant traing the \' statistic (P< 0.01), The nwrtclity of monozcgotic smokers is nat greater than that of the monorygotic nonsmokers, and it ean be shown that, re- gardless of the natura of the association, the monozygotic and dizygotic samples did not come from populotions with the same amok- ing'effect (P < 0.01 cne•sided test). For women of either zygoeity, no arreiutent or statistically significant differences can he seeR In the analysis tarried out above, former smokers were included among the smokern. Table 5 shuwa data for nonsmokers com- pared to fonner cigarette smoken. The asso- ciation with smoking among dizygotie males born in 1901 to 1925 is statistically signif- iant using the X' statistic (P < 0.02). Table 6 shoaes mortality of the older age grottps (bore in 1986 to 1900) by amoking status, zygooity, and sex. No increased mor- tality assodated with strtoking is found. Table t shoas tttortality data for pairs where one member is a nonsrttoker and the partner smokes only cigars or pipe or both. There is tw excesa mortaifty among the smnk- en. In fact then are fewer detttha among the Arch EnuGon Xeallh-Vof 21. Oct 1970 T0020565 f -' _. -, x:-...._... TTFL 0305477 ~
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6,1-w ~G ++ I o 0 STET!N1ICS -°G l~T (1 ClO~]G 0 GY Joarrnal of THE AMERICAN COLLEGE of OSSTEfRICIANS and GYNECOLOGISTS Volume';9 January 1967 Number 1 f arental Smoking Empirically elated to Pregnancy Outcome PAUL S. UNDERWOOD, LCDR (MC), USNIt, 1(ELVIN F. KESLER, LCDR (MC), USN, JOHN M. O'LANE, LCDR (%iC), USN, and DWIGHT A. CALLAGAN, CApT. (%1C), USN, F.A.C.O.G. IN naCt. xt:Aas we ba~ro beea frequently semadc of the threat of tobacco prod- vcts' eSens on various orgem aod s)3taos. With the erseasitig •aumber of women smokers am the ever-growlog concern about envimnmen al aIIaets on the fetus. the rda. WL».W.t a.w. trar The Opiei er aspttbne eemHeed haeie an tba privaa e n af tFb whea aod an a0t a be aonurusd as eiol eor n rMaalne rief ethvlwa of tbe gutnu )cedieiee and Surpry e Navy Deyanment. r the navaF aervla at bn9e. Subminr4 publieadea May 77, 19" risneee. From the bsteuleat sed Gsxoalc9faat Seraa, U. S. Naval }Ins9ilal, National Na•at M.diW Cenfer, eah btd., the Obnenieal and Gynn enloaieal Se e, U. A Tea stuien, China Lake, Catif., and U A Naral Heapaal, On.t Lnke.. DI. Thuda w dua Mn. lane A. Maesxt, 4t.3.- of the Ollla D'wmary. N.tional Institute 0f 5(eatal Heal , for the statistical anals+6. sad me Du. P anea Diritton; 6er.au Ot Sfedtrina and luracry. Naq Depaamea; fer brhnipl ao- PA - 000493 tionship of smoking to the outcome of preg. oarlry has become an Important issue. Animd experimeats"" heve domond strated a decrease In birth weight, an ia. ctease in perioatal mortality, and a deaease in fertility when the mothers a•ere exposed totobac0ostooke. Sanpg and Wallace reported an incease in the fetal heart rate with matemal smoking. Hellmea rr al. con/lrmed that Gnding, but noted a frequent increase in heart rate aa the cizaeue was Iighted, suggestina more than the simple trattsptxcnml pamsaTe of tobacco by-produeta. Reportsa... s.. u. u. v, t4 sy t. tu.e shown that fnfants bom to mothers who smoke were smaller and the incidence of prematurity was larger. O'Lane fa+nd isttaau bom to stnoking mothers to be 4S inm sburter md to bave a slightty lower Apgar Pq TIMN 0154230 TIFL 0305508
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i 502 JOSEPH D. MA?ARAZZO AND GEORGE SASLOW that o e certainly ahould not con- clude f om Vallance's negative results with crude laboratory measure of sugges ibility that the issue is closed. As a atter of fact, the study by Horn t al. (1959) of 22,000 high school students in the Portland, Orego , metropolitan area shows just such i fluences. In addition to many other ' portant findings, their data reveal that: (a) the percentage of smoke s is highest among children of familie in which both parents smoke cigarettes, and lowest in familie in which neither parent has been a smoker;(b) the percentage of smoke s is higher in Catholic paro- chial s hools than in the city public school,andislowestinthesuburban public high schools; (c) the per- centag of smokers is highest among studen s who do not participate in any s ool activities; (d) the per- centag of smokers in this young age group is inversely related to the educat onal level of the parents; (e) the p entage of smokers is higher among those students who are behind their a e-equals scholastically, thus confir ing the findings of Earp (1936) and of Lynn (1948). Emo ional status mted cigarette smok- ing. s part of his study of 903 smoke and 903 nonsmokers, Lilien- feld (1 59) utiliud a 31-item ques- tionnai e made up from a list devel- oped b Stauffer et al. The 31 items selecte were those which differ- entiat a "normal" from a "neu- rotic" up. Examination of the 31 items d by Lilienfeld (1959, pp. 264-26 ) makes clear that this ques- tionnai e utilized items very similar to tho contained in the MAS, CMI, nd the Saslow Psychosomatic Screeni g Inventory (see section below). Lilie>hfeld's findings (p. 269) were that 'the responses by cigarette smoke on the questions eoncerning emotional status were consistently more 'neurotic' than those of non- smokers." Nineteen of the 31 items reached statistical significance: 11 at the .001 level of confidence, 4 at the .01 level, I at the .02 level, and 3 at the .05 level, all in the direction stated. The remaining 12 items were nondiscriminating. An additional finding (p. 278) was that the smokers had had a signif- icantly greater number of hospitaliza- tions (p<.001). The author sug- gested that while the excess number of hospitalizations may reflect neurot- icism, they also may reflect other reported associations between disease and cigarette smoking. LiIienfeld (p. 276) reports that an analysis of the reasons for these hospitalizations is now in progress. These findings of Lilienfeld, while in agreement with the findings of Lawton and Phillips, and our own, are important for several additional reasons: (a) the sample was large (N-1,806) and was an adequate representation of the entire normal adult population of a large city; (b) the sample contained two groups matched on four important variables (age, sex, race, and social status); (c) there was a reliability check on the findings. Unlike the two other studies which used selected subgroups in the population (university under- graduates, student nurses, psychiat- ric patients from a large medical center, and VA hospital patients), Lilienfeld's study dealt with a non- institutional sample of adult nor- mals which was more representative of the total sample of adults in the United States than were the other specialized samples. Yet the fact that his findings and those of the other investigators agree is striking. At this point a comment is in order about a potential shortcoming of theae three questionnaire studies h a F. C TIFL 0305546
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CHAR4CTERISTICS OF SMOXERS AND NONSMORBRS TABLE 2 S8x AND SmO62NCl (Smoken in the United States Aged 18 and Over) ;rs with d social lf these ' as of eumma- eadings. IASLHS he data stracted Only a ;e of 10 his very - ameri- °gins in hus no '3 0-17 .Is have >ast 50 :hange, id ado- flation- +rs that in the pproxi- o) indi- lcreases ividuals sp (25- for the : about . Addi- :ing are (Ham- Heath, Dickin- , 1957). r-: Malea T tal Group" R lar Smoker (cig., cigars, end/or pipes) S oked Oceasionally N ver Smoked N Data N % o! Total 49,581,000 33,566,000 68 2,448,000 5 10,704,000 22 2,863,000 6 Regular Cigarette (only) Smokers 23,411,000 47 Females 495 N % of Totsl 55,096,000 14,953,000 27 2,259,000 4 35,785,000 65 2,099,000 4 14,953,000 27 A Abatncted from T>bla 2, V. 57. Haeuul, Shimkia. snd Miller (1956). 7hlt tutal doo act saual tbe wm of tha aamber Ywwa below Enuw .ame .mokto, yrimaAr aaoco nuln, oft n amoka piGet aad dian. a. wen w dprettn, aad thaa anyy vea iadividual mar be tepmmtad hwine, anoa es Resak smoker aM ooce r a Reaulx Cip..tts (on1s) 5meker. Sex and smoking. As is suggested i Table 1 and summarized in Table 2, fewer women (27%) over age 18 t an men (68%) over 18 smoke r gularly. In women, smoking is al- t exclusively confined to ciga- r ttes, whereas with men 68% smoke r gularky in one form or another, w ile only 47% regularly smoke ci arettes exclusively. Although not s own in our Table 2, the data g thered by Haenszel et al, further s owed that in the year 1955, in the 1-24 age group, 34% of males had s arted smoking by age 18, and 50% h d begun by age 24. For females in t e 18-24 age group, 16% had s ed smoking by age 18, and 36% h d begun by -age 24 (Haenszel, et al., 1 56, p. 56). Although the figures on percent s okew for young males have changed li tle in the past 50 years, young wom- e have shown a substantial in- c ease. Whereas few women now in t eir 40's and SO's smoked at an e ly age, 20% of the women now in t eir 20's were regular smokers by p habits (Kinsey) smoking habits of women born in the past several dec- ades are very different from those of their mothers and grandmothers. A progressive loosening of "moralistic" attitudes in the past 50 years has been suggested as a contributing factor. Evidence that the relationships shown in Tables 1 and 2 between smoking and age and sex are not unique to the inhabitants of the United States comes from a recently completed study of the smoking hab- its of the entire population of Israel (Kallner, in press). Except for minor differences, the age and sex relation- ships were similar- Race and cigarelle smoking. The United States data of Haenszel et al. (1956, pp. 36-38) permit the follow- ing conclusions: The age and sex dif- ferences noted above hold for non- whites as well as whites. In the United States, there is no difference between the percentage of whites and the percentage of nonwhites who smoke. However, quantity of smok- ing differs between whites and non- whites. Among smokers, there is a e age of 18.5 (Haenszef, et al., 1956, 17). Thus as is the case for sexual TTFL 0305539
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CHARACTERISTICS OP SMOKERS AND NONSMOKERS 499 rs who had had - had attended ~hool, since age of school com- orrelated up to be concluded school, college, 'ol there is an .age of smokers udents still in study of 6,374 Texas colleges off and Rigdon d just such an 3% during the study by Horn, iolomon (1959), s of the 22,000 s in Portland, se observations gh school years. increased from n the freshman enior year. The for girls was =shman year to year. Raven anecdotal ob- Dking habits of group of college by J. R. Earp >f 177 students .ed to graduate; ;1.8°Jo failed to .940-45, p. 139) hat this finding on and reveals cing being the ire; individuals :s might be the >king. kers and non- to achievement I characteristics 1 (1948) showed s who do not Variable Socioeconomic Indes: Mean Range SQ: Mean Range Anxiety levela Mean Range Psychosomatic Symptoms: Mean Range Cupe of Coffee: Mean Range Liquor Score: Mean Range TABLE 4 M8AN9 AND ELNCE9 O) SMOrEi9 AND NONSYOYE8.7 PsychiatricPatienh Student Nurses (N-40) ~ (N-114) I Non• Smckeo emokera (N=31) ~ (N=9) Females Non- Smokers smcken 60.2 57.9 44-73 14-77 93.6 98.8 77-109 79-12 28.9 25.9 13-39 6-45 12.1 13.9 2-23 1-44 2.8 4.2 0-8 P-13 1.22 2.06 1-2 l-6 48.6 11-73 117.6 103-130 12.3 3-26 6.3 0-22 0.9 0-6 1.0 1-2 • Meen dWercnc<s Itnifxant at Ibs .eS kvd. - Mr.n Neennae.Veeleant a the .001 lewl smoke, on the average will gain more weight, make higher grades in school, fail less often, cause less disciplinary trouble, make better scores on psy- chological tests, be troubled less with respiratory diseases, than the occa- sional smoker and the habitual smoker. The study showed also that smoking and poor scholarship do not always go together, iil that scholastic averages according to age favor the nonsmokers in some cases and the smokers in others. Participation in spnrts and cigorette smoking. Lilienfeld (1959) found that smokers had participated to a Univervty Undergraduates (N-140) Females 'lales ymo~~ Smoken s okers Smokers 46.2 43.6 42.1 49,8 45.4 11-77 i1-71 k1-73 11-77 11-73 118.4 110.9 109.2 107.9 109.2 103-12 87-129 92-122 84-130 89-131 14,8• 12.0 15.3 11.0 14.7• 3-34 5-28 6-45 2-30 1-33 8.2• 3.7 6.l 3.3 3.9 0-IB 0-14 0-18 0-12 0-19 2.6` 1.5 2.7 1.0 3.5" 0-10 0-10 0-6 0-6 0-12 1.2• 1.3 1.5 1.5 2.2" 1-2 1-2 1-2 t-5 1-6 greater extent than nonsmokers in certain major sports (p<.01), had participated more frequently in a miscellaneous grouping of other non- specified sports (p<.05), and, at the time of the interview, were par- ticipating in a greater number of sports (p<.02). What relationship, if any, there is to Heath's finding that smokers had more combat duty in World War II than nonsmokers, and Ianni s finding of more driving accidents among smokers, is unclear. These studies will be described below. Driving accidents and cigarette smoking. Data for this variable were TIFL 0305543
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Y,ycSdunwl ddld~ I~O. V41. $7. Nq 4. 493-513 Fsy. min 3ri0. ates i. F. ;:cd >on: 385- . aze Soc. R., +AS, ctd > in ol I (31 isUTiCc: TSfi~ PAATcr.:AL M,.': i~~ 'rii0 ~ C:TED ]'1 YJ' ) BY COPYRIGHT LAW (TITI.F 17 U.S. CODE . PS CHOLOGICAL AND RELATED CHARACTERISTICS OF SMOKERS AND NONSMOKERS JOSEPH D. MATARAZZO.vm GEORGE SASLOW Ueiners:ly of Oreron Medim! Schoai Consi ering all the evidence avail- able nc the writers themselves cannot doubt thaan extremely high degree £ association exists between cigarett smoking and lung cancer. This ociation has been reported indepen ently by many different investi tors who cannot all possibly have co mitted the very same errors. The ev dence appears to support strongl the hypothesis that cigarette smokin is a major causative factor in~ung ncer. The present status of the cau e-effect controversy is de- scribed ost cogently in the articles by Back tt (1958), Hammond (1958), Little ( 957), and Rutstein (1957), the revi w by the Study Group on Smokin and Health (1957), the book b Northrup (1957), and the public s atement by Leroy E. Bur- ney.' A Rutstein (1957) has pointed out, the eneral health problem posed by ex ive cigarette smoking is of sufficien magnitude to warrant con- siderati n now of what preventive measur may be socially possible and des rable. Although data now clearly i idicate that any reduction in the nu ber of cigarettes smoked by an ind 'dual reduces the health hazard Hammond, 1958, Figure 6, p. 338) the percentage of smokers who ha e given up smoking is quite low, f ing somewhere between 10 and 18. % (Haenszel, Shimkin, & Miller, 1956, p. 24; Hammond & Percy, 1958, p. 2956). In vi w of the current widespread + S n General, Public Health Service, Vnited S tee ikp.rm+en! er LSeatkL, Fd..ea- tion, and Welfare, July 12, 1957. interest in the smoker, it has seemed to us wise to review the literature on what is known about the psycho- logical, personal, social, and situa- tional characteristics of smokers and nonsmokers. Few systematic studies exist which are concerned directly with this issue. Some of the pertinent findings are summarized below. Two of the best studies apparently have not yet received wide attention. The first of these was a study by Haenszel et al. (1956). As a supple- ment to the United States Bureau of the Census Current Population Sur- vey (CPS) for February 1955, smok- ing histories were collected from ap- proximately 40,000 men and women 18 years of age and over. Survey data were adjusted to include unsur- veyed population groups (Armed Forces, teenagers under 18, and institutional population). It was possible with apparently a fair degree of accuracy for the au- thors to generalize from this repre- sentative sample of 40,000 subjects to the smoking habits of the total adult population of the United States (some 105 million adults). Adjusted estimates largely based on data from this 1955 survey, the 1952 survey of some 187,000 older men made by Hammond and Horn for the Ameri- can Cancer Society (1954, 1958), and a variety of other statistics-gathering agencies (Haenszel, et aL, 1956) indicate that the total number of smokers in the United States and in overseas forces as of early 1955 was close to 60 milfiou. Of these 54 millioa smoked regularly (everyday) and rhe rnt «asieeally (not evervdaY)- The numbv of regulrr and ecetaional smokers in 493 TIFL 0305537
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' PARENTAL SMOKING a y.1 y.Y I,•Y I . ~ yy daTA emte ne• I tl.nt. Meon ..{eAI d:11.n+au W..d, .4 ee11M1..• uMly 1. ,+si:.y Maan. N wN\.n. lia. 2 . lNrAl/. M.ae w1aAI d~la.nw. by .wk, al pp.y.., uaMdiM le..lwa kaAll. of l.bw. tKe eaa ' ele. a. Mero Nw .: M. /w on aAIM, uadty Ie nalA n• sieA/, jgq u,d a.a.el .wekW. ~ ttie rtW p w.n.nu n Iw. yw„p, QFMtWPI e/ lIl L..a L L l1:3 I_! 1~~ L_:~ ~J _lri~ l LI~T .. HEgS'YlEI6NT5 "I~~•, "'°" Of as signi9cenL the times as large as the diHereoee. Iotaats bom to signiRczatly small smoken. This diffe number of cfgarNt i8erenoe had to be 4.9 standard deviation of smotiag mothers• were than those born to 0oo- eneo increased with the amoked per day, rt:ach- ing 213 gm. for tl}e heavy aelakee. Heavy emoking did not s~gniReandy decrease the birth weights over group. The mean were essetttislly t according to fatb weights were s/go th bora to nonsmokin flag ao effect oo hi nnoking. Fgurs I ahows smekieg on birth w trimesses. 4'lte m9ats were detee those of the modatne irth weights of infaats e same when grouped ' smoktag habits. Thus same as those of infants mbtllpss, dearty lndiea- wefght from paternal the e8eets of maternal ight throughout sLe third n birth weights of afl tned for 29-34, 9S-3g, vY, H. N.•11Y I hwry and 39-42 weeks of gestatioa and compared according to mothers' smoking habits. In each group the aonsmekers' iafanu were heavier than the group i mean wei_eht and a progreesive decteasc io birth weight with in. ereasity materoal unnking was adted. This was most apparera in the 39- to 42-wroek group, the dilktenoe being 204 gm. ta the same manner. Fig. 2 shows the e6ect of fathers' smoking habits. It does ttet show any relationship of birth weight to paternal smoking. Figure 3 shows the birth weights aaording to maternal smoking habits with mothers gtouped byr their prepregnant wefghu. To each group, progessh•e deercases in infaats' btnh weiehts were denqastraud with ittereassd smoking. This excluded the possibility that the observed decrease in birth weight was doe to the smoking mother's weighing less thao the aonsmoking motLer. Also, this Ipn. 3 TTMN 0154232 TIFL 0305510
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a 496 signific heavy whites than th percent for non ference evidenc is invol Alth( ers and race, hi fact tht differer ers, the found I than th author this dif Mar ing. T (1956, elusion sexes, of sm, widowe among marriei individ age 45, of smo dividui are mo never s individ (in the slight age grt Lili.e one asl etal.,i presen ferenti the srr signific 0un Amonl portio emplo; JOSEPS D. MATARAZZO AND CEORCE SASLOW ztly greater percentage of technical workers, although having cigarette smokers among the highest incomes, have a low (more than one pack a day) ere is among nonwhites. The age of white males is 13.3 and white males 6.9. A similar dif- is found for females. Indirect :e suggests an economic factor ved in these differences. )ugh Lilienfeld's (1959) amok- nonsmokers were matched for s data show that, despite the ft their own birthplace did not Ltiate smokers from nonsmok- : parents of nonsmokers were :o be more often foreign-born ose of smokers (p <.001). The states that the implication of ference is not clear. ital status and cigarette smok- he data from Haenszel et al. pp. 44-46) permit these con- s: For all ages, and for both there is a greater percentage )king among divorced and :d individuals than there is both married and never- I individuals. Among single uals (never-married) under one finds a smaller percentage kers than among married in- sls of comparable age. There re single individuals who have ,moked than there are married .uals who have never smoked 18-45 age group). There is a reversal of this trend in the wp over 55. nfeld's (1959) results bear out xct of the findings of Haenszel a that he found that, although t marital status does not dil- ate smokers from nonsmokers, iokers had previously married :antly more often (p <.001). :patiort and cigaretu smoking. ; males a slightly larger pro- 3 of the unemployed than the ied smoke Professional and smoking proportion (also see section below on Income). There seems to be a complex relationship between social class and smoking patterns. White collar groups (professional workers, managers, etc.) have fewer smokers than are found among craftsmen, foremen, salespersons, operatives, and similar groups (for further data on this "social class" variable see sec- tion below on Socioeconomic status). It was found that military life is asso- ciated with a higher frequency of smoking for all age groups (25-65 and over) ; veteran age groups were found to have more smokers than the non- veteran age groups (Haenszel, et al., 1956, pp. 38-44; Sackrin & Conover, 1957, p. 5). In the sample of 1,806 Buffalo adults, Lilienfeld found that smokers change jobs significantly more often than do nonsmokers (p <.001). Additional (longitudinal research) findings on the relationship between occupation and cigarette smoking have been reported recently by Heath (1958) and McArthur et al. (1958). These data are shown below in Table S. Urban-rural residence and ciga- rette smoking. Present urban-rural residence differentiates smokers from nonsmokers sharply. There is a smaller percentage of smokers of both sexes and at all ages in the rural farm population than in either the rural nonfarm or in the city population. Rural nonfarm persons resemble closely urban dwellers in their smok• ing habits. Among males there is little or no variation in smoking pat- terns from one region of the United States to another. On the other hand, the 1955 Census results show that cigarette smoking is more prevalent among women in northeastern and -At west Uni Sac: I mai (19: Am Tat in smc por Th larly annr of th to $7, the droF L, sok sma to a of .` wor ,Lkr I rat, reg, flat ter reg ag, inc co cig ag- (P sm AI TIFL 0305540
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CHARACTERISTICS OF SMOKERS AND NONSMOKERS 501 .ted by us were .ble also. The ed in each case nifest Anxiety -easonably well astionnaire de- scious anxiety x Matarazzo, ylor & Spence, 4, for the 40 : mean anxiety smokers (28.9) is very high he mean anx- amples of nor- from 11.0 to d nonsmokers. xes for the 40 -e very similar by us for two :ations studied iversity School :t Clinic (Ma- hile the lower two normal in the range elected groups ,, et al., 1955; Table 4 make normal sub- igher anxiety s. While the =ans are not reach statis- )5) in two of ow a similar ale university ative to the two_ normal 1xiety scores nokers, place it along the ,h is closer to psychiatric g of a higher nokers, rela- tive to nonsmokers, was not obtained in the psychiatric population may well be a reflection of the higher over- all level of anxiety found in both smokers and nonsmokers in this population. The amall number (nine) of nonsmokers in our psy- chiatric population does not permit us to establish this point. Psychological knsion and cigarette smoking. In an interesting study of 63 (normal) medical-surgical male patients and 32 psychiatric male patients in a Rhode Island Veterans Administration Hospital, Lawton and Phillips (1956) used the Cornell Medical Index and another specially devised questionnaire. The CMI is a well-validated 195-item ques- tionnaire (Brodman, Erdmann, & Wolff, 1949) covering a wide range of somatic and psychological symptoms, not unlike the Taylor MAS. The authors concluded that among their normals, "Heavy Smokers," when compared to "Moderate Smokers," showed a greater number of signs of psychological tension (12 p values from .01 to .05). They concluded that the present data appear to indicate a very real tendency for this present group of heavy smokers to exceed the group of moderate smokers and abstainers in various indices re- lating to presence of "nervous" traits. In both number of somatic and psychological com- plaint.; the heavy smokers seem to resemble the emotionally disturbed individual more thaa do the moderate smokers. In the man- ner in which they are willing to describe them- selves (on the Adjective Check List of the second questionnaire], the heavy smoken .,. [deacn'be themselves as] less agreeable, happy, and relaxed ...(and specifically rate them- selves more often asl nervous and grouchy (p. 401). In addition, it was found that there was a significantly higher percentage of Heavy Smokers as against Mod- erate Smokers in the sample of 32 psychiatric patients than in these 63 nonpeychiatric medical-surgical pa- tients. Thus two conclusions from Lawton and Phillips' study are indicated, First, that Heavy Smokers among the normals are more like the psy- chiatric patients by these various in- dices, and second, that psychiatric status is associated with a higher frequency of smoking. The first conclusion bears out our own observations on anxiety, dis- cussed above. The lack of compa- rability on the age factor between our own two normal samples and our psychiatric sample precludes any useful test of the second conclusion drawn from Lawton and Phillips' data. Suggestibility and rmoking. Stimu- lated by the statement made by 29 out of 35 college student smokers that they had been influenced to take up smoking by their friends, Vallance (1940-45) studied the suggestibility of smokers versus nonsmokers. Using Hull's body sway technique, he found among Miami University stu- dents (25 smokers and 22 nonsmok- ers) just the opposite; i.e., that the smokers were less suggestible than were the nonsmokers on this meas- ure. With the subject having his eyes closed while standing erect, the suggestion was made by the ex- perimenter that the subject was to imagine that he was falling forward. Under this set of suggestions the smokers swayed only 3.83 cm. while the nonsmokers swayed 5.27 cm. Other measures of suggestibility con- ceivablycould show different results, since it is well-known that Hull's measure is not highly correlated with other measures of suggestibility.' There are such strong a priori reasons to think that parental and peer influences are strong factors in the initiation of the smoking habit TIFL 0305545
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_~p/FD4C s^\,`„R ~ssJ;`e' -°R1A'~ • FIFIiJIS }" ACTA pA DIAT SCAND SUPPl: 143;[41, 5`71)1g64RANTAKA LIO.. P,/fWASZ,HOeKERT. 0; JARUINE;A,. P.A,. PFLTDfIEO. T., HAAVID 4A~Elk1~,6„ H~RYNEt{ P`; pARTANf=N..T.. K[LP1, Y.. MALENEM TROQ . A, AlL4$ A41C'fE(t. IL. DRELL, P., tdEEMINE 3:A. ; `ro\f" G\M 1 ;i R(SK (i1 LOW BERTH WEIGHT IPIFAtlT° A:9D PL.-Ct'-L '-" °2!l7'ECTEVE STUDY OF THE EIQLOGICAL CHA^ACTrR(ST(CS AID `.: _-';:iQfl[C ~IRCUMST.'diCES ~F MOTHERS [Pt 12.06`J JELIVE,°.IES !'M lhFTH F1NLPA 1966. A D(SCRIMUiANT FUWCfIOt{ AAALYSIS. /TRA ISLAT:3 FROk! SINGLEi INLAND, REP6ESFsli~I1Z6~ ~!QOXIMA?Ef:Y ~ IN ORDE ,~Ta OE~~E~ . ,~ ft f 1~ RAfA RtSlt' dv PEi~t-. RTnet?Y'~~A L -~. '~~-.. . ~vR[lsF~'~~:~STUtk`f.dlC21;9~5 - . Ttr~ S"ru Y,e v ~ 7~- rl ~s4iC : , tsoAtrt"s tt6r 4m OK''ititc t oi.To. THE P*%ata- :._: ,.. ;,.. _...,._.., _...:: +...:.: W f AMR' R .~1~t:SrElBkrOF 80'.1'~.Tll~~tt-' E ; ?I4,Hat D" 'n* *ISt. OF _TNE . ` Pl~~[?{A_T?~4 ~~GwOk ILor PtOt OGf FS +nt~ g~u7PL~{1~F1ST/{t) ~~ Yi1{tff, L(11f ~STS OF,Tt1E FORaER: _ Fi~. ~05 l~i :'. ~~~.~~~~61~tHk Tw;',tmc~:40'9r uY$cAter((t"r" ..- MORE, b EVEN.AT LESS. THA IESS 1'H! :~R 7 THE JfF ~i~E7~29F~L:. •I vBkSEMTED.: S LYSTS f~tE T.OfX3 FI6EKS,fk-CAi.ES YIHkRE ['f WAS . .F.-ir ... .,~ . . f TNE Etdf.DF PERI- S. ~ ANll SH FJP! AIR[71[6 .~~('IE` ~Q r CKBO : TkII FtYLI01tt9~ yR~fAI StR7H ttEIGitT ~ Gff CRSES~:I`Bi SER'fN tIEfGHT ~ C~S~ES:'.'AI~~LC)~8[RTli'.kE2GHt 2SW S OR YAEtFR~TfQN~ 3Ii ~tRI~ WEIGHT tvERE" SFGlELFLCAfIT .~ S/A}~{Q~FA~AG~S ~t THE 468 :{.9W.flIRZFk IiE[GHT IFtFaYT.i. ;l PA - 000492 ._ -- TIFI, 0305504
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nnd vfs• con- xids .hicb arnt. -dvte and inn, j sind zro14 ich< :rrem Fert- ;dg, Sehieselbein, V. fnsdong, W. fundong, Gmmbueh. Rcmplik, Schasuer, sod Immich::Cimtine and aexriaademsit In seceral «trospetrive and prospective statistfcal- cpidemiologicaf studias, cigarette smoking has been connected wids coronary heart disease (1, 2). In the so nllcd „Frarrungfnm Stud,v" (3) dgieette smoling has been rewgnized as a„r'vk factor", which, together u;th other faaors, may lead to an euliec manifesation of coronary heart disease in smokers than in non- smokers. From a statietinl point of ciea, the relation betaeen coronary heut disease and cigarette smoking is not very strong (4), but considering the very high mortality by coronarr hesn diseas4 all risk factors are ne e:ninent impornaee. With regard'to the influence of tobacco smoke verc little is known about the mechanism, which tmy possibls- contribute to the manifnration of coronary heart disease. In an autoptic st:udr on patietus sho had died of other than heart diseases, .jt'ERe.aett (3) showed that smokers had earlier hiscologitally demonstrable manifestatfons of coronarv sclerosis chan noa-smoken; moreover the extent of coconary sclerosis has been stated bc.it.2RSecs to be correlated with the number of cigarettes rnnsumed. From these and other investigations it may be cottduded, cHat the main nuse of coronary heart disease is corotute sclerosis. With re¢ard to the in(fueete of tobacco smoke, the problem arises as to which consdtuent of the smoke is responsible for the erFea described. Administmtion of nicotine leads to the «lase of oreeholamines- epcciall~ ftom the adtmal medulla. This has been proved by the ending of inerassed excretion of arechsalatrdnea and their mea- bolireo in the urine of smolcen (6, i). In addition to rhe phamw <ologlal effsets, especially inctaae of blood pressure, the teleasa of admnaline and nondrenallne nuse metabolic edeas uhen «laud, namely inerease of the blood mgae le.el and ris< of the commntmeion nl free farp-aeids in she blood. The release of free fatty acids by nicafne via rdase of ateehol- amincs and subsequent aaivation uf the trigllceridc otenae of adipose rissue has been shown to oecur in esperimentsl aninals (8) and also in humaoa (9). Beause it has been proved, that ehs etTea taka pfse also atter adminhtesim of tobaao vtwke ne an assume, that this e3ea is due eo the phanseologiol eReue of nieaine. . . \Vith regard to these facts, sevetaf autftoes bave tried to ecaluate the effect of nicotine on eaperimental arterio- scierosis and on fat metabolism in humutt. CsoeftR.a- Ln.LNon-ta (10), tsnsves (I1), Hsss (12), and Grtosco- csAr (13), using diffecent ecpedosentil assays, observed an increase of arteriosclerotic changes, following the administration of nieodne to rabbits fed an acmiogenfe diet. Several investigators found elevated Wood choleeterol levels after nicotine administtsdon (10. 13, 14). In humans contradictory results have been obtained; incrased eholesterol levels in smokers have beea found ' sn"I by Goc>u.. (15), KAecovcv (16), Bsto.zeSrew•Aar (17), .:d,en: and Kt.~-ex (18). The concentration of ,B-b'faoproteins ! in the blood of smokers has beea found by neerly all :iGcm! the above authors to be elevated, while the level of ! triglrcer+dee in smokers was mosds unehanged (19, 20. 'I~rs21 22) or decreased (23, 24). The above mentioned esperiments vere perfornsed h (ch3! 2• uin. Cheru-um kfin. B(oehem.l8. )ahtg. f9701 fieft3 r as i generally for a reelatssrly shoa peaad; mcotsae 191 used in addition to other arteriogetdc factors, especially cholesterol feeding. Because of the above mentioaed results and the pharmamlogical actions of nicotine, we incestigued the effect of nicotine in the rabbit under the prolonged influence of moderate doses in order to approsfmate as closely as possible the conditiotu of smoking. The diet was normal and conditions were comt.nt. At the same time, the biochetoical and morpho- logieal effects of chronic nicotine utminisnation exre tested. ivlaterinl and Methods V,hite 4w Zalsnd fennfe nbbio aged 40 dan a-ae disided into a nicoc'vu trated gtoup (n - 33) and controls (n= 23). At the end of the experiment (man life rime+'_0 months) 2? ani- enls of the nicotine trested group and 17 animals of the control grtwp s,ese uill livfng. 2 months after the xare of the e..penmem ae*eral aninuls felt sick aith coceediosn. Thercfon allanhaals o.xre rrmted with a sulfonaetfde prcparatfoa (Gandf Vit A - Da - E) and a .itamin preparation (Vitamia-f:omplect \'bamin- BCI.-) (both peepsration Dr. Aentfehls[ S Co.• hupheun). 3 mentha later sevenl animals suticred from a arurssalic infection af the upper airea.l which was ttared wkb paremenl applin- rions of 1(I0mg chlotampbmieol (Panaitt, Boehringe; ]Iann) heim) subeuasmualy dailye). In add'uion to the deuh of some of rhese anitmis we losr snme animals fsom tumors of the smrn- ach, oraries, .nd he orhita_ Ul animals tereieed ".Ustostisa f:" (ium of Altrogge, fagS WetGmtsatsl) ad libimm as stmdatd dirx without snT supplemene (eamposmon In?o: nw ptotein 161: raw ebte 13.9; fae 4.9; ash 73; \-fae eaaso smtenal 13.2). \"ireli,nr 7be esperimaltal grWp reraned 1.11 mg nimrine (ftee base)/kg body weight nno tims daily fmm \fotday to Fridxv and once daily on saturdays and sundap in the dcinking water. This douge ov, chosen uah refeaesce to nicotine amoutm sd- miniuered by other amhon aich subaequent de.ebpmau of anedoseleeoais and wirh segard to human smoking beha.iour. P.se nicotine dou was adspted during the finc ucdo of ehe experiment ta the ierteating veight of the stffl growing anismli Temporary wiehdnuaL of drinking wvter before admhsiseatio,r of nimtine auuted the uptake of the total nicaine dose cithfn abcm 30 minuteat moreo.ar, tht nlenttne eenetlltfYian in the blood and in se.eol otgans has bee nrimated in a iurther grnup . of animah, undergousg the »me srestesmt (sae under "reeuLs'•). Orrlrfs tw/re4 wea pedartned asaerhl). Far .erreM/irerr For eahradon of fee meabolrte, blood was with- dnwn frum an esr, .ein afrer 9, tO and 20 months. 'Witlsdrswal of blood "s performed always ae the sama time of day and thetc fore under the same dicuae caesdfriom. Fne Jaw,h addr: Copper mashod, a¢ording to Dt:.eosrn (75). P8erp6rlip6: Esrhmtion ot organie pbosphorus in ptoseia pt.- dpiure scmrtling to WaosRee (26). Enri/hd/saj esi4: Ffydmc amic add method of Geass'rt (Z7). Beu.1 d fsre rbeh+feef sritb the Lneaauxv-8cacsauu teeion tnodided according to W.as- so. (26). Tord lipJds: Yanillln method according to Cx.eeGa and Csusoc.nr (29). Aairity of the GpepreMn L'pme u desctibed by Z$ccvctt and Eaaesswsaa (30). Qd'wle ufiwaias .J rbe umi/irf /retefee .f J.rry aai4 aed or;ear wv performed by g»thnmatograplsy in a Fotas- Sraenr saasaa prepared immediately after u<rifice. >L.thllarion of htry• acids (Scstseuat and Gucertat.w`) (31). .lppaneu: Hewktt-packssd \tddd $10, FID, meeaf rolumns 48", lmgth h We ere •ery gratefuF to Dr. H. Senar.t, Imtitue fue Sfikeo- biologie und fafektionsltaankheitea derTiae der (:ni.aaid,: M0o• chen, for d'pgnosis and shenpaurfe suggexime- r0020488 TIFL 0305386
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160 Physicia s' Altirudes f oward -1 heir 1nvolve eni in Smoking Problems of Pa±ients` Doroilry E. C een, Ph.D.," and DanieI Horn, Ph.D.f A recently pleted survey conducted by the National pinion Research Center attempted to atxiwer a n ber of questions regarding pltvsi- ciatss' opiniors about smoking and health. A ques- tionnaire •v,u ent to a random sample of'S,C00 practicing phy -cituss drawn from a univer:e of r 212,5W. In aI), three mailings were made, svith a total of Y;SC6 pond'uig to one of the three mul- utgs. i sample of nonrespoadents was followed by telephone inte iews; 283 cases svere derived from these tal1;. Th tesults of the telephone calls were appropriately weighted, assuminirtbe telephone r spondeats u•er like the nonrespondents rather lilce the mail r pondents. Of particular interest t us are those q tioar concerned with the physi- daris percepti of his respoasibiliry to his patiena., and of his be avior with them in relationship to stnoldng and h Before repo patient.vnnts laroer prenorti cvnvince his p 'It is the p .. tots polled ( +T indinsee that tonY The resu How do th doctortelis the h. g these results. I would like to diugs obtained two years ago fzam general publia Thev very definitely far help in smoking problems: ree in a national sample interviewed ago agreed that it is the doctor's his patients to stop smoldog (6r, per cent), that doctors should set a good example by notsmoldng (69 per cent), and that the,v should be activein m Iseg speeches to thegetteril pubiic about the harm Inesf of cig:uette smoking (69 per cent). Also, 75 per cent felt that if a patient wants to quitt it is the iocme`s job to help, and 84 per cent believethat m patientt will not quit unless the job to convin about two v dbouttwoof look to the phy meation some a sample of th io do so.. opinions agree with those of doc- is of the receat physician survey ovvtrhelmirtg majority of the doc- er cent) agteed tvithh the statement 's respomibility to attempt to tients to stop smolirtg.' An even m(SB per cent) agmed that iE a stop smoSdng, it is the physieiaris -rresrmerl at ;raoenal Foram on OHtce )taneee+nerrt of Smol,lny P hkau, :.lanbn btomr Hntei, Chieqo, tulnow, April 11, 1966. "Cl~it{, prnmm eteareh Sectton. lDireao.- \'ati mi Cbnnnsmmuie for Smo:ine and Hmlth, \',tinn I Center fnr Cnronle Dfi.au Contnl, Our-m ~i Dis Pre.xnnon ard EnNronmentol Con- trol, Dnhlic H nft Serrim, U. S. Depomnent of Heatth. Fs:ucatian, and R'etfam. Arlinqteq virainia ' 12 Too,05'73 PA - 000487 IG c ~oa ~N' .---. responsibility to help him accomplish this. Seventy- two per ceot agreed with the statement "It is the physician's responsibility to set a good exampla- by not smoking cig:trettes.- Two oi thr-e think phv- sicians should be more aelive in speaking hefore lay groups about cigarette smoking. Physicians unquestionablv recognize cigacette smoking as a serious health hazard. ~fore th:ut SQ per cent associate smaking .vith chronic bronebitis, Iuag cancer and en:ph,vsema, and almost as r.un,y associate it with peripheral ntscular tlisease and cor- onary artery diseose. About three of four physicians associate cig.vette smoking tvit4 lan'ngeal cancm leukoplakia of the mouth at:d lips, aad oral cances Only about half of them indirste that smo::ing' is associated with any soft tissue lesfon of the lip aurl mouth„md onlyone•fourth associate it with blad- der cancer, indi©ting a much lower ncceptance of the sigpi6cance of an,v relationship between ciga- e rette smoidng :utd these conditions. Most physicians, then, do see cigarette srnolm3 as a hedth haard and feel responsible For chanqin, their patientz smoking bchavior. What do they do.' The doctors were asked the following questsnn- 'Among your cigvette-smosang patients •vho ds not have any condition related to smoldng, ho« many doyoa advise to give up tsgarettes (orrns: down sharply) as a general health pteeaution?' and were asked to reply by sa.ing all, almost all (95-99 per cent), most (63-45 per cent), ete_ down tv none. This question tcas followed by a similar ques-- tion asking about the proportion ol patieats vitk each of a number of speaBc c»nditions who-.rere given this advice. Looking only at theproportion oE doctors giving this advicr to 'aB' or "almost nll' (9Fr106 per cent) of their pataents,.ve find that:,S pec cent oE the physidam. say that they advise ail or almost all of their patients who do not havramr cen- dition related to smoldng to quit or to cut doavn- This is in sharp contrast to the proportion-b8 ier cent-+vho give this advice to their patients uit'a lung and pulmonary conditions. Other conditions, and proporrions of doctots -1ving advice to tdt or d- most all lnttients, to quit or to cut dotvn, are (in descending ordcr): peripherpl .vrasiar disease; Sl per cen t; hatrt tvndition, 74 per aenp upper respir- atory condition, i1 per cent: peptic ulcers. '1 per cent: mouth or lip lesion. -1 per cent. On the othrr DIS. CNEST- vnl _ 5e un a SE.'TE",78ER 1.963 TIFL 0305485
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vrtllmt IR Low-bidh.wright in(ants and maternal smoking 28,7 -.,,L I ~uu,Vh,Uer2 tc,.vmas' swa.,eo H<ertT M PREV;OUS va(aryqHE/CS NONSMOKER , SMOKER e,lnMn ,lL PREONINC,(S SMOKER [ErCaE SHC ST1qTCC CY PAST SMOKER S[rJR! SHt tadT S4aMNa 0MI +M1linkpr ynRCmtl \r• [.01 O,MIbLeSYr Wbnesnl )eDt of totmnokon. 1l\c tow-bitth-scci;ht itxfants of moking ntothcts hasro considornhly lower pct'natnl tmft:dity r,tcs Jmn low-birth- w LL infants of nonsmokiug n+othert. nokcts difCcr gt'catly from nolv<;noken In nundxr of modo-oi-lifc cbatnctcristics, . Th latter epixar to liso at a tnuch slokvcr aut tnoclcrstc pare than srr.okers. Thc two gra ps were fouuu to diffcr alao in somc bio gic chamctcristics. For cv+mplc, tlu age at mcnarchc is Io\rcr far stuckcra than no sntokcrs. ldcd to thc;c are the findingT of the prc nt paper thnt the reproductive per- fon snncc af futtu'o smokcrs is much liRc thx o( smekcn cven in the pm:otf heforc th ' startt'd to snx+kc and that past smokers' rep nduetice fxdonnonee before they ryuit stn Wxsg is mnch like that of umucn who nl'F •r s[notrd. 711ese findings mise doubt and al3nee L i / I e Q ,e xc r~[e[xr 28, Fip B, Per cent of lovbirdt-+rcight btuk• infants by smnking statur of 4heir methm . lower d dur. , p < same stbom :duced ic.s as onsbip uctive cd on, 2 data onned ;en•cd thcm- ukcrs, t'uups the that, ke in t!are, o the i ;ttc c cf mhrr :re n fanir, utl'cr thae PERCtnr Low-S+4rer(roHr inrp-5 r"-_ .~.x ~.-...._ NG 4 fcrn with the inUautoricc development of the fettrs. Rathcr, Ihe evidcncc appaus to support thc hylwthcfs that the Lighcr inci- dcnce of low•-bisU+-t•riyht :ntants is due to tIta rmoker, not the nnod•ing. Hosecrcr, the fmdings relatc to a single study, and thc snmplct arc not lnlgc cnough to ixxestigntc the role of correlated \:uiablcs- IItxause of the imiwrtanc implications of tlxso fiudiugs not ottly to Iho qucstion af smoking and. prcmaturity but also to the other aspects of the problem of smoking and health, the conclusions must be considered tentativo. Tte findings, hoeccer, m:rkc a strong case for Uxe need to incesti3n:c die pmblcnt en murit lasgor sarnples of births and to fncludt: for study many morc vvi- ahics. I thank Dr. IIra J..nn den Bcrg far as.fsennce in :uuly'sis Ond tifrr. Dorothy I'ricdumn and Mr. n ing t the proptnitinn that cigatettc smok- nets as an ctatgcnoxrs factor u'hidt intcr- Fnd Slmub ,rho perfornmd thc praggcnmming and eomputed tzlstdatione. R!7/!!NClS theL T.. +.R(an: TA.nrrn .nJ ficnl+h. 1. $imrynu, l\". I.: Aa. OnsTWt Cvw:cct. 73, Spvu,Pfidd, Iltinoiy Iffi?, C:horlc+ C:'I'hnina+, 08, 1137. ' t'ubli•hvr. 2. Ifm-riut, A., 11iUwi<z, \V. Z., and Ilytten, 5. hfurdock, U. E.: Nebr. State \ted J. 48: P. B.: Lancet 1: 771, 19G2. 11, 60i, t9ti.'x. 3. Yillumun, A. ]..: t'geskr. Ixger 1N: 630, 6. hlanteN, 0. Ua ti. Z. hlyd. J. 0; 601, 196 s. 1962. 7. hlac\lallon, lt., Alprrh M.. and Salbcq E. 4. YerushalutY. I•: In Jaxxtes, G., and Rnxen- J.: :Sm, J. yaridrmioL. 82: ?i7, 196.5. TIMN 254630 TIFL 0305522
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Oo:d- dtoes: 71, 5. xnd 109: 2anon, 1971. Pardf, Pmg- :iuical Press, 969. PA - 000494 ~. . x„ Infants with low birth weight born before their mothers started to smoke cigarettes 7. YERUS.HAL'MY, Ptr.D. ' &rkrfq and Oaklnnd, CalifOrnia TRe ttudy eeaplorrr thr eccrtinn ah•!Fo thr innrau in le;oi7r<A-:odtht infantr te tmnking grnridot is dus tn f6e smokirot nr the smoier. The nvlhod u'at that eJ iare,tirnrin6 Ihr rrpron'ar/ir< $rrlarmanu of fu/urr, neo@crs durin,{ fLr peuiodr ' bafaro thry reqnirrd the ,mndiee Aabip I:.rar found ehnt :r ,eAe suut.q,rrstfy berame nnekerr had a hi;h inri:rr.rs v( fo:n-lirth-rvn;Fe iairnL aha dv.inq ;he period brfau ihry reartcd to menhs. lt eat rnnrludrd that tbr /ndiner raite dovbt and areve e;ainrt rhe proyorition that <igautu mtakinS ea er an rsoyenvur farter whieh (noerfaru a-itlr eLr iatrnu/erzne da~etoyv:urt o/ th<(eeu- Ra:hu, u,r r.idrner apprerr to rupper< Ihe hypothuir tha the 4iy1•.er inrideuee rf tom-s'vth-mcieht in(ants is dae te We snaF.uq not fha srnoking. . 1y u s t. who smoke <igarettcs during p natxy gico birth to a much larger pro ortion of '9otv-Uirth•sceigiu" infants (iv'gBing 2,500 orams or Itiss) than uonrcn wh do not nnokc- 11tis observation, frnt ma c by Simlaons in 1957, has becn c•an- fir cd by many imtstigators.r-ye An in- cse so in the incidence of low-birth-weight inf ts has very serious implicalions, for it is cil kaowu that infants wcighing 2,500 s or less suffcr a neonatal tnortality swtc (tlr risL• of dying in tira first mondt of lirc) mo c than 20 titrsot as high as tl:nt of hats•i- er i tfauts." rrom the finding that rclnticely nr as many infants of nnokin,r mothers are of low binlt tmight than am tlrosc of non ntoling nsolhcts, it may be expcncd to far 'that isdants of smoking snothers suffer ' Frvm Child Ilralnf nnd Drvrlnpmrnt mo7 Sevdier, Dinisinn ul /lin•:nwtirq 5, oi Pu6tis l!<.Lh, Uui_euity of Cnllfnrsin, and the %ai:rr Faandalinn Rrrru!ei, Inr!iena< and 11:e Permmern:r ,7frdf<e7'Cros p. . Supparted br Crun/ Na. I1D On7tR a1 tha 8atienal lnrtimla nf 11<alth. • Rrerived for pvbliraeiee Oetebn 4, 1971. . Repint reqarrtc JSG7 Ifo;re St.; Onkfend, G•chlurnia 1916,11. 277 considcrably highcr, risks or carly dcath. Howcv•cr, mast studio did not find such an increase, atxi the treight of etidence is thnt infnntx of snwking motLen do not e:~Terienec higher pcrissttrF ,nortafity rntes tSast infants of nowmlacg tnodun- As of July, 1971, +~t were able to identify 33 studics rqsorting an incmise in thc inci- deuca of low-birth-weight infants tn smok- ing mothcrs. or these, 15 stopped srith this obsenation and did not in.cstientc thc rnor- tality ratc.r'a Tlurn .vcre 4 sludic.sraa" bucd on larger nenples u•hicis uill be discwsed sefmrnccly: T}:c rernaining 14 studirs ditidd d eqnallyg secensa~ found no increase in mor- tality tate, and seveu'e"' fnund so:ne in• crease. Ia iuany of the latter, the incrra.c was hot very large. For e.ampdq sotne of the autlton commcnt as follour. "Sinra thc total numbec of deaths was only 47 v:Is could casily be a clonce eTeat,"r' "Womcu tcbo stnole have a slightly highcr inri;lr~n.c of aboninuc,"rs "it w:u cmtduded thnt thc ftntlinros trern not cansistent tddt thc ht-- potlmsis Ilut there w;ss a direct c0'ece ou fctnl or iafant hctith:'r' \foremrr, the pmbability that 7 of 14 studics, cacb of which was 6ved on sonw 2.000 prrgnnnctrs, wadd miss a 35 per ccnt increase in nroc- TIMN 254624 .TautntnCta~.~r:St~uira.a$1..~~wC~t£a~t~- ?74a4(.S jI47~, TIFL 0305516
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CHARACTERISTICS OF SMOKERS AND NONSMOKERS 505 :nown Study :rant Study), lected "nor- .vere studied juate years ve been fol- d question- le present- he smoking he main ob- ut have re- McArthur 1958). Their of anecdotal ns which are id for which Id be con- 61 (24.2ojo) 7.7070) were 96 (38.1%) During the mokers and nber of con- which are )le 5 taken idy are im- irts and letters ioa adjusted, com- portant because, as a 20-year longi- tudinal study, it contains the only published observations of their kind. The findings point to many psycho- logical variables which deserve fur- ther study. However, since many hundreds of variables were studied by the several Harvard investigators, and since apparently so few vari- ables (those shown in Table 5 and a few others) reached statistical signif- icance, there is always left open the question whether or not the reporfed findings are due to chance phenom- ena. IvIcArthur et al. are aware of this possibility (1958, pp. 273-274) and offer some cross-validational findings from two classes of recent Harvard undergraduates. The bulk of the findings, while very suggestive and stimulating, needs confirmation, however. FACSOBS INFLUENCING THE INITIATION OF SMOSINO Despite the likely importance of this subject, little systematic study has been made of the possibility that the factors associated with the initia- tion of smoking may not be the same as those associated with its continua- tion. In our own opinion, there is considerable a priori reason to be- lieve that the factors which motivate people (especially teenagers) to start to smoke are probably very different from those factors which help per- petuate the habit once smoking has gone on for any length of time.' The earlier described study by Horn et al. (1959) of 22,000 high school students points to factors as- sociated with the initiation of smok- ing (parental smoking habit, par- ticipation in school activities, etc.) which could hardly be thought to r To examine this hypothesis, personnel and facilities of our department were made avail- able te ]-lera ef the Amerlmn Cancer Sedety. have equal importance for continua- tion of smoking in later years. This age group provides many oppor- tunities to study both peer and parental influences associated with teenagers' beginning to smoke. The recently published results undoubt- edly will prove interesting and pra vocative to other investigators. Ex- cept for the few indirect hints arising from the 20-year follow-up study of Heath (1958) and McArthur et al. (1958), little is known about why Americans continue smoking once they have started. A second study has been carried out by Phanishayi (1951). Although the number of subjects studied was smal] (48 male college graduate and postgraduate students), and the country (India) not our own, he was able to gather suggestive data on self-reported reasons why these col- lege men (mean age 25) began to smoke and also, once having started, why they continued to smoke. Pha- nishayi prepared a 48-item question- naire on which each student was re- quired to check for 24 items those reasons, and only those reasons, which were associated with his be- ginning to smoke and, for the re- maining 24 items, only those reasons why he continued to smoke. Some of the items in the two lists were identical. The two parts of the questionnaire thus had certain ele- ments peculiar to each smoking stage and certain others common to both. At the end of the 24 state- ments in both Parts I and II, a pro- vision was made for the subject to give other causes if he had any. In addition, each subject was asked to rank-order his own choices as to the three most important reasons why he began and why he continued to smoke. The 48 subjects were told the purpose of the i:.restigation and TIFL 0305549
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504 JOSEPH D. MATARAZZO AND GEORGE SASLOW port that oking helps them keep down their eight. Brozek and Keys (1957), in study indirectly bearing on this p'nt, have reported that over a S-y ar period, smokers who discontinue smokjng for a 2-year period sho a statistically significant (p <.001) eight gain compared either to emselves or to a control group of okers who continue to smoke. T e smokers who stopped smoking 510w ed a weigltt gain of 3.73 kg. (8. lb.) relative to their own previous we ght, while the continuing smokers sh wed a weight loss of .50 kg. (not sig ificant). Hammond and Percy (1958 recently have confirmed this weight ncrease when smoking is discontinue . These authors found that, of 333 ex-smokers, 246 (73.9%) said they "ned weight when they stopped sm king. LONG-TH STtJDIES OF SM08ERS We were ble to find only one such study: a 2-year longitudinal study of 252 smok s and nonsmokers from Harvard C]kge. These were all . participants in the well-known Study of Adult Development (GrantStudy), a long-term study of selected "nor- mal" college men who were studied during their undergraduate years (1939-1942) and who have been fol- lowed by interview and question- naire from that time to the present- a period of 20 years. The smoking data were incidental to the main ob- jectives of the study, but have re- cently been reported by McArthur et al. (1958) and Heath (1958). Their reports contain a wealth of anecdotal and statistical comparisons which are not easily summarized and for which their publications should be con- sulted. Of the 252 subjects 61 (24.2%) were nonsmokers, 95 (37.7%) were moderate smokers, and 96 (38.1%) were heavier smokers. During the 20-year period hea.vy smokers and nonsmokers showed a number of con- trasting characteristics which are summarized in our Table S taken from Heath (1958, p. 387). The results of this study are im- TABLE 5 CON}RASTlNO CHARACTSRLSTtCS OF NON9MOSaRS AND HEAViER SMOaPRS- Most stable sonality Major in co : natural aciences Carsen: che istry, physics Like: seiena arch worker Physical sden Bland aAect Inarticulate We11-integra Dislilae: sales anager Psychotype: brotonia Anawer questi nnaias promptly ~ Armed : Navy; well-adjusted, twncom- bat duty Respiratory te: slow Sighs and lows: diminished Re9ezes:in eed Less akahol s coffee s 7 Heavier Smokers Cultural Lack of purpose and values Less well-integrated Practical organizing Less stable personality Major in college: social studies, arts and letters Careers: social relations, educstion Like: judge D'ulike: science research worker Psychotype: viscerotonia Delay answering questionna'vea Armed Service: Army; less well-adjusted, com- bat duty Respiratory rate: rapid Sighs and swallows: increased Reflexes: decreased Moce alcohol and coffee TIFL 0305548 port tudi publ The logic ther hunc by tl and able: few icam quee find: ena. this and find'. Har of t and how D this has I the ' tion as t] tion con: liev peo: toE fron pett goa Hor sch; s0ei ing ticil whic . 7 laciii able :l
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d. M..L ARCNIVF.S OF INTERNAL NEDfC1NE thi Claw it sern Nn4 by defieition, since tha~mett were selected as "nortnal;" it is etml" to sntoke or not to smqlae as the euy be. It is not to be ecpeeted that fin inga could be exaetly duplitated in nu ther seament of .ociety. The renmltn, ho r, suggest stmngfy that smoking o mo than a suPer6cixl ha6it over4yed imimtely opon a. group of mm but h snme otigias at fettst in persooatity and p siologie eltaraaetistlo. Such chacacter isti a eny have jnst aa muh right to a place Iu e etiology of ditesse as the to6aem e ke ingatloa itselL To-prove such a po' t, of eoarat: further inwntigation is ited.' 'a f'cltetC Hooper IM~, 124 Prof®ces REPERENCBS LI L[aArlhs C. G; WaM4ca S, and Diduv anq J.: The Parelmtotq of Smnldns, to be yub L Heth. C W., et af.: Wlnt Peopte .4n. GwEetdin, Mau., Huvaad Uni.eni:y Prca, 1947. ,J. Wdis, F. L, and 1Vopb, W. 4: Omacvding TraiNt fn a Seleetsd Cdkae Grouw with Sane Refartnce to Grter Iuereta wl Wa Rern.db Cw:aL P.ychuL Moarop. 1S_t27-230, 19G6& l YeArthur, C C: LugHem Vatiditt nf the Strvne Teat ia Two Submltme; J. AppL PareMl. Jaa+6ast Lnd i Medv. I- P.: CoRete Men ae War, &etap. .1erAan Aeademy of Ases asd Sckntn. 1057, 6. Sdtac, C Ct Wdfs, F. L., md MeTennn. E 8.: A Relatiomhip Betreaa Sheldpdan Somw Inpys and Pr7e4a»q 1. Pmaa.. i6:471-4.i6. t9/t 7. Bm.dr, 1, aad Keyy A.: Cianaee ef Body Weiehr, is Naend Men tVhn SMp Snatuas Gprttlts, &lace 125:I29X 1957. & Ioh:eay B. E; &u" L. and Du1iq, R. C; A Teat nt Phyeid Fhneas /oe Strenuau Fsertimt. Re., emd& biaL t:wt-lOS, 1912 TIlVIN 0000629 3U T075911 TIFL 0305535 ---•---c
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e 7 AL - lY9asily' ~ ~•b+oryioMC I ohe,e Smo,enf I u mare >uJ Etoosc /1'le 0 ( ' 1 3 0 0 1 : in the ,two 'aencoo of dif- ' nonsmol:ers ::nciated with -.:re to phy:;- That t- 'vcr stnokers ;,Dkers. 1ne '. on Sorrner h isjusfified . ire Inconolu- Jietory. IC Ls 'ry to obtain ~ ~o>sible to rang noele, "ac muse of to this ^ ar_ still Tnere are are mtpQlt- four qsey men oe- -'- and sui- ~ I" be as,co- <ntic twjll$ men and '•'il': is of rtature of ...,.x,a nc~t b1ORTALITY IA' 5.110K1\'G D/SCORD.iVT TtVt•VS-FRIBERG ET AL 519 g may be a symptom of a mrtain petsottality type. under study and also to get new data on smoking and an eocioeconomic and other encironmentalfaators% g up all the evidence, the data that part of the greater mortalityin smo " is not due to smotung per so but to factors aasociated with smoking. It t t be valuable to follow the groups 1. Th Hwfth Camteurncss af Smohiny: A P.b- tic Hea lA S.rr(n Rerieu, publication 1696 US Dept Haelth, Educniun, and R'dfort, Publie Hsllh rvice• 1967. nvi.d 1968. pp 1-227. 2 Hi trued E: Smokina bt ralanoa tn Ihe death mta of ne miWon mee and remsa ia Hseerel W (cd/: E demialoyal $adr o/:Can.r and Oths' Chronte D'u.a.er, asavotmph 19. lis Dept ol Health, Eiuatiott and Welfan Public Health Sen'ice. Nationsl Gaaer Instimu. Bath..da, ?Id. 196& Op ' .2pL . & T6. Lba of tWNe in .pidemtala`Ital enldteF Report a\YHO mcetiy ol isa•atidaton. Aem Gmet S/ d IStl09-[2B, 1966. 4. C.i iH R: Thr Tmin h}ethod in Epldrmioloe• iral St en Cluvnit Diu.aa, thasis Vnfveni/,. olSkrJr6 Im• 1956. A ' naistriu la the atvdy af chmhic disaaa v.itb part cular nlaeme to the relation at smoktaa to caNl lar sad lxdttwury diseaes: Repo[t hom a line ia Saa Ju.o. Pu.rto Rico, her ]9e9, eta Sfed Seand, tn be publi.hed. 6. C.4 rlot lt FriEera L• Junwn E. at at: Hr rpintary ymplens and °on~`JU pKtorit' in IWlns wlth nfe ee lo smeYin{ hnbitp >a sPidemiotn.i- mi sh+dy with a,.iled pvnlionnain. Arrh Enrirnn Hntih 1 726-737, 19eie. 7. Ced el R. Jotuwn E. Lundman T: On ehe vsiidity o rnsiLd tlwaCOM.ira la d'uaaaaina "an- jina pec ors" aod "brenchitia." Ar:h Enuirart Hrafth 13 T3y742 19BG This invectigation w•u .uPPO.4ed by xrrtna from the Atnevic.n A4ediaal Amacutdoa Cducafion aM Research Foundation end tha Sw'edish \lediwl Rn aaarch CounciL References B. Cederb( RL Urban factor and prwslears ef rnpir.tary sytaptoaa end "apina p.ctorii': A studY en 9,tea twin psin with ihe aid at mait.d ytstionatirea. ArdY bne4vn Heahh 17Gil.7ie, latie 9. Cederlbt R. Friberr Y. Jenasms E: Hereditary r.chn and "andiat pscmris': A atudy en twin pairs with the aid cf eviled auesaoansirsa Arch Ent'iwn Health 13t39;-IOrI, 19u7. 10. Cederlol IR Edton NIA. Fribe:g L, et al: Heredibtry hetotw "apootonaou, ceu;h" and "smokers eouth": A rtudy on 7300 twin.paira..ith tha aid ol tneiled Vu..tionadnm Areh Ent,irwr H.alth Iisial.aaQ i96T. ll. Codertat R- Fribeq L Hrubtc Z: Cardiovss• misr and nyiretory synptonra in relatieo to tolnc- eo smoking: A study on Atnenean 1,1. ARA Lnviron H<alt41et831.aiQ lee9. 12. Cedarlel B, Fribw9 L Hndet 7•: BeckrruuM ol "atletW pea•IMii': fteladonsbip bawvM amnking end other soeinl eud mvitonmenul faeton. R<ad Leran the Fitst tnrereatiar•d Sympwfum on Twin Snuliea P.omt. 19n9. 13. Lundmm T: Smoldat in Mation tn mronary heqt dixaw and lun,t luacdon in rwins: A ro.t..in wnttel itudy. Arla dicd Scand 180(suppl iuda. n• 1966. ia Csderlaf R• Fltdstus B• FribeR L• Cancer in inotos)'aotic and ditylNtft twirs Raad befon the Fint Interaalionel 5ympwium m TwinSludies• Rome, 1969. . 61OOERN LOSS O? VALUES T becottu ill theae days or oth.nrisa to stnFaL in [ifa'a patude is perlwpe a mite sof [lwn for a beboon to Lll lrhind the trepp In the .vilds of A,f[ica. Tlte tneraphysi<t of tural inequaliry• be it physiml or mental, senea the abplutist well. Our hrosh, nois uarld is doing strattge ehin(s to people as man takes sntnethfng of a beating from nvn. Th, medical student and physfeian would nat be expacted to escape the mtdern ali tiaa. ' It d be tem.rtable If attitudea wer: not se debaseed as the enrirone• where the rapi poUution and deterioration of the bipsphete. and the aubtitution of the "experi. enci for the artistic ars orders o[ the day. I. it to be waadeted that mannen, diptitY, seni , mont~, and elhio and initiative are at something of a disceunt^ The limw are co tive to etxlz, to vulsarity and to the dwaluation of honesty and aserry. of divti y, Iove• rppect, and fair play,-,>,ring CD: The Phyxaiaas t;onatituHon. The Ph of Alpha Ome;e Alpha 32:3-5,17,1989. Arch Enuinn Health-Vol 21, Oct 1970 -Cp0205Fn T1FL 0305481 ~
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. igh having ave a low see section seems to be :ween social -ns. White al workers, er smokers craftsmen, operatives, irther data .ble see sec- nic status), life is asso- equency of (25-65 and were found m the non. szel, et al., 3~ Conover, 06 Buffalo iat smokers more often .001). Ll research) -ip between e smoking +cently by thur et alA own below and ciga- irban-rural okers from :ere is a :ers of both :ruralfarm : the rural population- resemble their smok- es there is -ioking pat- the United other hand, show that prevalent astern and I ?s CSARACTERISTICS OF SMOKERS AND NONSMOKERS TABLE 3 Irtcous erro R.ecvt.an Ctosesrre Sxomaw Males I 1954 Income % Smokers % Smokers Less than 61,000 39 19 52,00047,000 56-60 28-33 57,000 and Over 50 32 23 • Abrtr.cted from 3advlu red Conu.v (1957, pp. t-t)• western states than elsewhere in the United States (Haenszel, et al., 1956; Sackrin & Conover, 1951). Income and cigarette snwking. The main findings of Sackrin and Conover (1957), from their study of 18,000 Americans, have been abstracted in Table 3. It is clear from the results in the table that regular cigarette smoking is, in fact, related to re- ported annual income. The proportion of males who smoke regu- larly increaus from 39% of the men whose annual income is kas than SI,000, to 56-60% of thos in four income braclreta from $2,000 to $7,000. For men receiving $7,000 and over, the proportion of regular cigarette smokers dropa to a littk over 50% (p. 2). Less than a fifth of the women whose per• sonal incomee are lesa than S1,000 a year smoke regularly, but the proportion iecreases to about a third for women receiving incomes of $3,000 or more. Abcut a fourth of the women who receive no personal iacome (largely hume-maken) emoke agarettes (p-5). Income appeats to hava a greater effect on ntn of smaking than on the Percentage of regular emokeis, although differences asso- dated with age and other population charac- teristiu were noted also. The majority of all regular cigarette smokers smoke from 10 to 20 cigarettes daily, generally regardless of age or income leveL Enough men exceed this raage to bring the ovetall daily average to 21-22 cigarettes for male smokers. The daily aver- age.for women... is 14-16 cigarettes daily (P. 8). Socioeconomic status and cigarette smoking. From our own department, Allen (1958) reported the smoking Femalea 1954 Income 497 Less than t1,0o0 $2,ooo-g4,ooo $4,000 and Over No Money Income (Homemakers) behavior of three different groups. The first was a group of 40 psychiat- ric patients from the Massachusetts General Hospital whom we studied by means of individual psychiatric interview of a special standardized kind and by a battery of individually administered objective and projective personality tests. Of this group, 31 were cigarette smokers, 9 were non- smokers. The second group consisted of 114 female student nurses from a school of nursing located in the north- west, of which 50 were cigarette smokers and 64 were nonsmokers. The third group included 140 male and female university undergraduate students, also from the northwest. Seventeen of the females were smok- ers, 31 were nonsmokers; 54 of the males were smokers, 38 were non- smokers. Characteristics of these groups are given in Allen (1958) and Matarazzo, D4atarazzo, Saslow, and Phillips (1958). The measure of socioeconomic status used in each of the three groups was the HolCingshead scale (Hollingshead & Redlich, 1958), an index which combines own (or par- ents') education and present oc- cupation to yield a single socioeco- nomic status score. As can be seen in the fust row of Table 4 below, no relationship was found between socioeconomic status TIFL 0305541
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AMONG N(5 ':Ai:1ATIVE lDENT I CAL TO PURELY THOSE GRO MIGRANTSr ACCORDINGI TO THdS ITYPOTHESIS. THERE.'SFT~O~L~D.9~~OT1iER F'ACTORS CON- TRtBUTIN 8 ( RTia wE URBAN `lH El:FECT. O OF SING4 u 01fl.U: ..-z . - z i ,s~ivs3e '" STUt!Y, p1tDYH04Is . A ~~IRTi+ w PROSPEC7 YE NUND , ,. ASSQCi B RiNATAt-MOR~`~ f; M~lc~wl AGE j l7 ~ ~REFYr~ t~~3RfFI ~ PARtTY p SOEi B1R WEt. NT ~ ~ ~ y ~ ` ASSbc, P R tNATAE ~NoRT~' ~~r""[ { FfiATER ~ ~ pEt~ry i4E (6HT' DECRSA5E SOGlOE OMIG FE~Tt~R$.,~SS4:,PER1fitAT 1a, IG FACTOAS:~ ASSOGt ~ RTH }~~E~/~iH? t~~~A~t ftYf.~~1~YN~~JL°, FERtR Tl~LPtOA'(~ALfTY ; FlRdMATA ~10 INt3UStlkl G ~ i~L~F~S~RS AaSQC. ~ ~ x~~ ~1RTH ~tGt6T , CIGARET7 8 . r4 E L~IN .S~ DECREASd P{I 4 ~~.~~~~fLEHL~`Af~BTEQIS Q ~ ' NQNASSOC ~Rl eNAfICY JN(~~~~T~ '~tn~~ N~tb~~~.3~ATEIRE ASS C. PERINpT MORTAL311 KA ~_ L STqfiE1AG y~` .~'~RtNA~AL NORfRtITw, MATERNA . WE1Gk•T A88o0.~RTH• WfiI~N~ N~QH~. 17~RAS5~t Ci BlR7~t WEIGNT CREA$1 MpTI RIfA~ ~P~[4~ ~IL~~~ PP~~jI>74E~4 PRRCAF,1 GY: MATERfFpL: ~ C4~ ~dKfNr~ NOI~ASS4C~ ~ ~i :@RAtfV SMONENG NONASSOC~. fSOHSMOKSRS,P3lt + ~~~. ~ ~ ` SjVetjIRTM w~j6NY pECRIASE QER1dAT L MORTAI:I.TY PHYStCAE YI~AGTIYl~ i OCCUPAT ONAI. FACTORS ASSOC, BtRTN;I'IF,L6N'G'~ihltll~TKIAY.,F&CTDf2S,N0?/ASSOCi r:,E 'iOH.Mt';RANTS. "r~`1E IDENTiCAL LOW BIRTH 'dE[,H" 4ATE; A~tTS AND NONMi^uRAN'f8 D0 NOT NECESSARILY MEAN THAT THE rACTORS 2E3ULTIMG [N LOH BIRTH WEIGHT INFAHTS ALSO '~ERE iHE LOW BIRTH WEIGHTS OF SOME INFANTS MAY 6E ATT?IBUrED MEBLCAL REASONS, AND BE RBMOVAL;LE BY MEDICAL MEANS. IN PS. WITH HIGHER TOTAL MQRTALt,TY.RATES:~THE'..GROUPS OF NON- TNC.SE REASONSMAY BE ASSUME)~~O`$E `IY4E l;08f(MPORTANT-." TO 7N6:,C.oN ::9~iR1~H W'EtGH'1";LM10N~RNNL;_hYr0ICNTsi.. LoM: Ht AND PERINATAL MORFAt 11Y; _.R9 E~ G`E'AL*f kCGHLa IK •vsda~,r> IN RURAL AREAS. hIULTIPE.E: pAC~ S~$fSC BHdv4Et4 1HAF THE , .. THE. ~TKiit VLQdec VAR'i 14 - $TU4CEB` FACTZ}f{S, y'ARRl.ESQ~.001. B4g~~~~'f'%k'flb~'{'AL d{~?RI~i /~K~ ., r
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232 Ycrushalmy Jan~>p 15,:772 vam' An. F ow.r. crn.mx nv.Ps GRryllaA5 SMGPIFO MLS1is Ma4 MirQNP/1Cre] NOfJSfdOKER PrPCENr IW-MRTNYtIGMr IMIYRr M oirr. . . ..:..-.J a ,<, . ~. xors ..:- p Q ntlureay enr,pu P.aa '~g. 5. P4Ir cent of Ioo•b'vtL-wclght nhite infants by smoking atatus of Iheir rnnthen- nuokess duriug iods before they startctf in mwkc tras sy ifica nclp higlur than that of infants of u thets who never vnokcd. (Y' = 0,69, p 0.01). Striking also is the fending that pnst smokers durinq the period huforu thoy quit moking gave binh to mta- tivcly few loTr-bi tls-wcighc infants. The in- cidence was sigui seantly lower than for in- fants whosc moth •rs stnoked during all their pregnaneics (Xx 5.61, p < 0.02). Ho.r- et•er, for many of these the ngo at ts{tfeh the u-oman start(3l t smokc aas not known. Canscqucndy, so a of tlso infants of pnsc +tnoken ma.' hase been burn duting peti- ads before thcir others acquiseed the smok- ins habiu. \tost of thetn, ltascn•eq must hate bccn bnrrt uritsg pctiods of nnaking. It is, tht•mfotcc, ndiartal that e>en while they smoked rrot cn trfso subsequently quit xuuking differed in their rcpnnluctice es- pcricnce front cot tinuous smokcrs. Pig• 6 ptcrcuts similar elata for infants of black tvomeu• It is seen that tlm tortdcncw is siudf•ir to du fomed fur uititc t1omen. Ho.rcecr, tlsc diR •runcd am of smnller mnq- nitudey cspecially in tftc eottepntisou of in- fm¢s hont lxfocc thein nxodtcn acrptircd the sntokinq habit T, tlt tlrrac nf infants whose m,nqu3u ncrt'r wt kcd. •t'he tii0•rrcucc is not - .ieuific~nG f,e -- 3.31, 0.05 < Is < 0.1). Iloacecr, die iucdeucc of low birth weight uf infauts of p:++ sowkcrs hom brfnrv their mothers quit m»kin, n;n significantly loscer dun of infants whose mothcn smokcd dur- ing all 9neir prcgnaneia 6,38, p< 0.02). In ordcr to adjust fcr pasity, th'c sarne comparisons were perfonned for Hnthorn infants onty. The numbcrss Mrore reduccd considenbly, but the sanso tendencies as found above were noted. Comment Tlte findings concerning the rclationship of the nwtfser's amoking to her reproductire pcrfantvntxe cannot ccuily be reconcilcd an a auscdfect ba>is• To bcgirx trith tlrc data are dericed frarn ohsenadms of ecff-fonnaf suhgroups• 71tc indicidunls luingoh;crccd rather rhnn the invcstigator made for tham• selces dtc crucial choice of being snsoken, nonsmokcrs, or past susukcu• The snAsgrou}n formed by sel(•srkelioo do not antinfy the Laeie rule fnr calfJ mientilie infercescc Ihat, n priori, groups brin, crnnpnnd }w alikc in nll fxrtincnt dtamctcri.tic:. It is, t6endom, asscntial to inquire more thoroughly into the obscrtrd relaiton>hips aad us intrstigntc critically tluir iurplicationx in the case of ssnokinq and low birth avight, a numbrr of qttcstions ari>t•. Snrokin;; ntnthcts have a hiqlu:r incialeuno of kntr.hittlt-~.ci,ght iufnnts, but fnfauu of nnnking mutlwn do not stdfcr higher lrcitcnal meirtality r.rt Y dun dwse ofnc of m pcria t.e;gf Sri in a The and. ~roq biofc age noa•: .1c presc form that tfuy rcpr nno ncvc T ati in" TIM1V 254629 TrpL 0305521
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JOSEPH D. SfATARAZZO AND GEORGE SASLOW TABLE t AGB ANn SYOa'L`26' (Regular Cigarette Smaken in the United States by Age and Sex) Ma4s Females I s«a se.6, Tnyt N emopn % Tob/ N Smcken % Total N Bmcken % 5,403,000 2,i87,000 16 7,160,000 2,316,000 31 12,865,000 4,BA3,000 38 21,820,000 12,378,600 57 13.660,000 8,933,000 38 45,500,000 21,311,000 41 16,034,000 7,L10,080 45 16,695,000 3,]95,000 20 32,729,000 10,543,000 32 6,522,000 1,296,900 20 7,361,000 379,000 3 13,383,000 1,678,000 12 49,581,000 23,411,U80 47 55,096,000 14,933,000 27 104.677,000 38,364,000 37 •~babute6 Irum TabL 2, 0. 97, Haeawl, SLimkin- md Miller (1956). the 'vilian, noniostltutional population, 18 yea and over, was about 51} million- n y half of this population segment. The n of male smokers totaled more than 31 mil n who sntoked regularly and 4 million who smoked occasionany. The number of le e smokers totaled 14 million regular and 2 Aion occasional (pp. 11-15). he numbers shown in the tables pre ented below vary slightly from the , due to the assumptions made, esp cially regarding the unsurveyed (in titutional, etc.) groups (Sackrin & Co over, 1957, p. 1). he second study, by Sackrin and Co over (1957), was a direct out- gro th of the study by Haenszel et L. and was based on a subsample of 1,000 of the 40,000 cases for whom H nszel et al. had smoking histories an on whom it was possible for Sac in and Conover to obtain addi- tio al information on income. The per 'nent results from both these stu ies are given in terms of Varia- bl Age through Income below. third study by Lilienfeld (1959) al appears to be a major contribu- tio in this area. A representative s ple of 4,456 adults (18 years of age and over) in Buffalo, New York, wa studied by face-to-face interview and multiple-choice questionnaire to det rmine whether cigarette smokers diff red from nonsmokers with re- sp t to emotional status and other sel ted charact.erisdcs. From this sa ple, 903 cigarette smokers were matched with 903 nonsmokers with respect to age, sex, race, and social status. The chief findings of these three major studies, as well as of numerous others, will now be summa- rized under their appropriate headings. PER.4ONALSITIIATIONAL VARIABLES Age and cigarelte smnking. The data in our Table 1 have been abstracted from Haenszel et al. (1956). Only a very few males below the age of 10 and probably no females in this very young age group smoke, For Ameri- cans, smoking apparently begins in the early and late teens. Thus no data are given for the ages 0-17 years. While smoking patterns have changed markedly in the past 50 years, and are continuing to change, in the year 1955 age (beyond ado- lescence) had a curvilinear relation- ship to smoking. Table I shows that for the two sexes combined, in the younger age ranges (18-24), approxi- mately one out of three (38%) indi- viduals were smokers; this increases to one out of two (47%) individuals in the early middle age group (25- 44); and then declines again for the older group (65 and over) to about one out of every eight (12%). Addi- tional data on age and smoking are to be found in other sources (Ham- mond & Horn, 1954, 1958; Heath, 1958; McArthur, Waldron, & Dickin- son, 1958; Sackrin & Conover, 1957).
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..efgh`ts in ;. mdy uomtuuk. is not encoWt- .ery vn- i by the td aWLLt ,ed one ious rt- ly early I ssnok- view so n thrsc :ly thnt f qum- to the >postso .ant is be sc- gation ,dc. at oe. N.hich :ht of n'hite mul- nictu D tile ved), ue,tt- ln4u. t i: vim~ser Z 1500 r000 t5J0 SCOO »00 t]00 e. 4. Per cent di5uihution of birth areighu in rcaious yreYnaneier (by hinors) and in study presnen<ios (e4+onzd) fer smcking aad no.umok- ,as; black graridu. ly botn to the multiparas, as well as those born to primipnras. The inclusion of die lat- ter assures that the two group: are com• pamble by parity and age of mother. It is scct that the distributiot: by birth weight as obtained by history and that ob. served in the study births asc nearly superv imposed one on the other. This is tmc for white and black smoking and nonsmoking gracidas. It it, thm<forg obvious that dsc d-ata are suitable for present purposes. Thcse data are now tssr.d in Ihe following way. Thc women ut the study divide thent- sel.cs in 4 different gmups: (1) those who never smokcd, (2) Ncomcu all of u9susc pre- vious- pregnancies occurred during pcriods of ,meking. (3) sntokors who wcrc delivered of live infants in the lsetiod before they started to emoke, and (4) past stnckers tvho tvere delivered of li.o infants befose thcy quit ssrroking. It is, therefore, posihlc to fm+exiigntc thc repiuductivc fx:rformancc of ttvttun of Cmup 3 during their nomtmking pcriotis and tcomon iu Oroup l during pcrl- ods of miokiug. 'I7te data am praented for all births that' oceurrel to wostsen at age 2i years or Iess and are conlt5etl Io women who atartcd to snsoke at thcsu ngc.c '1'his is dope in otdrr tow-binh-wcight infceb and muwrnal smoking 191 to nnrrov thc age ran-c of the wonscn in the 4 groups since agc is avociated with inci- dctscc of low birth trcight. In addition to the ago restriction, data arc limital to thosc obtained from mul- tiposas about thcir pretious licc births tvhich occurred before they came to the study. Year of birth of the gravida and of her previous licc-bern iu€ants had to be knotta, as ttell as hcr snsoking status, including the n;c she started to smoke. An esception with respec: to the latter tras for past stnokcrs, because at the bcginning of the study, ago tvhcn they started smoking %+as not asked of diosc who quit smoking. From the information on the year of birth of the mother, the age at which site sthncd to smoke, and the gcus of birth af hcr prc- viou licc-born children, ic was poaiblc to identify the infauts ttdso were Uorn before the woman started to smoke. IIirthi which occurred on the olculnted calendar year in which the woman started to smoke scere cicluded. Data nrc presented only for wbito and black ba.:das. ;1te number of inernt+ers ia Ute other etlmic groups in the sausple .cere too small and were, thcrcforq e.cluded. With the cxception of the amissiano mcn- tioncd above, all the lise births which oc- cur:ed in tile previous reproductive hutory of all muttiparas aro inciudud. 'lhere were 3,422 white women who satis- ficd the above conditions. They reported a total of 5,466 prottion pregssancies. Therc trero 1,635 Waek wosncn who r<Iwncd a to- tal of 3(!Oi preeious prmnancies. 17tcce can- stitutc tlu: study population. Findings Fig. 5 prc:ants hy ssno'sing atatw thc inci- dcutc of Ivsc-birtll-tvcigl¢ infants iul the pre. siosts ptr,4mmVcics of w$itc mothcn. Thc stnlsing ftulin,, relntes to infnnu born to future snso.erss durina thc pnriod hcforc tlsey started to snwke. It is secn that it is . as higlt as tlx incidcnce for inhutts of n5oth- en ntt of whose ptrgnancics occurred dur in; periods of sntoking. 74se incidcnm of low birtlt wt•iyltt for iuf:nns barn to fulure TINLI~S 25Q628 TIFL 0305520
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- -- - --~ i .,~~ Accsnt], 1772 Am. 1. Obirt. G,ncwL The pnrposc of this pnpcr is to inccxtigtitc the qucstion of nrm4tr roreus smokina usore dircedy by cez uatinq thc iueidcneo of lo+r- birth-treigltt in :nds hom' lo snMkr,t3 durin prrioc!s hrfnre tfroir nwahcrs startcd to srnokc. If .mro:iu~ ca<vcr thr..iurrcnic ht lose•birdtncci~h inGtnts, thmt tile incidruce nf lou• hinh n'c ght for infnnte Isnrn to smok- iqq molhcn rl riag tlw pr.rind before tlscy aeqturcd tnc su nkiu; itabit, shoald be rela- tivcly lo%,- If, n the ot4cr hand, thc hie~it incidence of lo r birth t,right is due to the :moker, thcn i shouid be ttigh for infantc of future stnok rs also nitr.n thcc ucrc born before thcir m thars started to sasokm Matcrfal an method The data a e derived frnm anr Child Health and Dc c!opment Studies (CSiDS), a comprchensit inresti;atiost of all prc- nancics that ccurrcd bctu'nrn 1960 and 1967, among w mon in thc Kaiser Fotmda- tion Health P( n in the Sart Prancisco-L•.ast Bay Area. •lltc Kaiser Aualth 1'Lin is a prc- paid mcdicnl e program. The members represent a bro d rangc in economic, social, and cducation h.itnctcristics. It is drlcicnt only in the tw catrcmu: the very afflacnt and tile very i digcnc portions of the popu- lation. Pnrticipation of the grasidas in the study uas ncnrly 100 pa cent. The tromcn uctc intervimvcd in Icptft on a variety of inedi- cnl, gcnetic an enstironrnenttl sthjectx, in- cluding bchac' cariables, sudt as smoking, cfrinking, use o contraceptive rnctitods, and tile like. Tlte m%YIMY was conducted at lcisuse and too place early in pmgnartey-. 7lta infonnatio wau tLus deriset prr><pcc- citrly before t! smnsau kttctr the outcmue of tile pregnat . 17te dtild cv.ts folloucd to ctaluate his pl ssicnt and ntcntal desclup- rm:nt includiny sun'ital asid tile duscLop- mcut of mngcn tal anonsalioa. For dte pup ars of the prc:essc imcstiym• tion, nvo main sets of data arc med: (1) the age at tvl ich die tvwssan started to smoke, and (~ the very t!etniled infonrn- tion on t!tc tc usans pre:inus tcpro.h.cti.c history. It is irn wrtant to state Grst that this r< to u i 3 is Y s ~ -or Msre.. -ourevm nw-wa.we w.T_/-"I f I I ~wo rcec aw sooa s»a ww u..n.r~oxn cn+us ylpkr0i ~ o t f t nV0 ]CO4 ls00 ]0>O SIOe .OM Flg. 3. Prr nnt d'umiLutlnn of binh rcights In preciov pn•Ynaeein (by hlanry) a,d in st,uiy preqaancirs (oburrcd) for nnoking and uonsmok-- inY srtute sravidar. . infermation, afthougls retros!sect!ee, is not likely to suffer frorn biases usually encoun- tered in retrospeetice atudies. It is very un- likely that die infonuation pro.idcd by the %..otnen about their sookusg habits and about their reproductice h!story tt'crc biased one by the other. The qurstion on prcviom rc• producti+n hfstory tsm takca rclaticrly carly in thc long intercicw. TUc question on nnok- iqq nas touard tile end of the intcrvicw so that about an hour clapsed het..xcn these hsa qucetions. It is, tfumfme, not likely that tile awsxtn'e ans,cers to the smoking ques- tions .rerc influenced by her responses to the question on hcs previous pacgnancics. This does not mean that evrry response is absolutely corrrct R9mt is intportant is Ihat anc inaccumcies in thr dot't not be sc- tcalcc for tlw probletn mttfr.r incestiqation atd tlsat they not be o( largc maamitttdc. Evidence duu snah tt'kctiun luts not ec- curre( is ptovidcd by b•i;:s. 3 and 4 tduch pracnt thc distribution by bitth wcight of infants of auoking and nornusaking white - and black gracidas ns rclarted by the mul- tiparas among theus on ^i[ their previous pregtmneics (by hlstory) <ont),awd to the distrihution of the stud,v iuf..nta (observed). The Iatter include all die iufan6 culueqaent- TIMN 254627 TIFL 0305519 tra set nr vi of of tr q' in W P' a
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llllm.....e'~ i soo JOSEPt3 D. MATARAZZO AND GEORGE SASLOW mad available to us in a personal com unication by Ianni and Boek° (fro Russell Sage College) who foun , in a well-controlled study, that in a group of 161 drivers who had ust been in a driving accident, ther was a higher frequency (76%) of c ent cigarette smokers than in a can oI group of 196 nonaccident drive s selected from the same driv- ing pulation which had only 54% curre t cigarette smokers (p com- pute from their data is <.001). The num r of ex-smokers was 13% in both the accident and nonaccident contr l group. .4nq~iety and cigarette smoking. The .50.'• YC80LOGiCAL VARIABLES IQ and cigarette smokisg. The three groups studied by us provided data for this variable. IQ was de- termi ed by the Wechsler Adult In- tel!ig nce Scale for the 40 patients, and y the Otis Test of Mental Abili for the two younger age grou s shown. As can be seen in Tabl 4, and despite the adequacy of the I range covered by our three samp es (77 to 131), smokers do not differ from nonsmokere on this vari- able Thus ft can be concluded that IQ is probably not related to smok- ngi he relationsfup between this flndin and the previausly cited find- ing t at nonsmokera tend to earn bett gradee is unalear and points to the n d for further rexarch. How- ever, t should be remembered that, as poi ted out by Super (1949, p. 90), 'the rrelation between intelligence tests and grader is not especially high ... the modal r's being .30 to '[anaii.,F• A.. & 6aek, W A stady of the relatbnpiup between mo[or vebitk atddmta and cauitaln cbaraetetistia of driven. Un- publish manwaipt, 1P58a three groups investigated by us were studied on this variable also. The measure of anxiety used in each case was the Taylor Manifest Anxiety . Scale, a reliable and reasonably well validated 50-item questionnaire de- signed to reflect conscious anxiety (Matarazzo, Guze, & Matarazzo, 1955; Taylor, 1953; Taylor & Spence, 1952). As is seen in Table 4, for the 40 psychiatric patients the mean anxiety score for both the nonsmokers (28.9) and smokers (25.9) is very high (p <.001) relative to the mean anx- iety scores in the two samples of nor- mals (means ranging from 11.0 to 15.3), both smokers and nonsmokers. The higher anxiety scores for the 40 psychiatric patients are very similar to the scores reported by us for two other psychiatric populations studied at the Washington University School of Medicine Outpatient Clinic (Ma- tarazzo, et al., 1955); while the lower mean scores for the two normal groups also are exactly in the range typically found for unselected groups of normals (Matarazzo, et al., 1955; Taylor, 1953). The results shown in Table 4 make it clear that, for young normal sub- jects, smokers have higher anxiety scores than nonsmokers. While the differences between means are not great, they nevertheless reach statis- tical significance (p<.05) in two of the 3 samples, and show a similar trend in the third (female university undergraduates). Relative to the nonsmokers in these two normal groups, the higher anziety scores among the (normal) smokers, place the smoker at a point along the anxiety continuum which is closer to that characteristic of psychiatric patients. That a similar finding of a higher anxiety score among smokers, rela- t1Vf in wel all smc PoF (nir chi; usi F smc 63 pat 1 par Ad j Ph ii bi e de•. is tio J Wc sor. ~ not ~ aut nor con sho psy fro: tha the I ten smc em lati nur plai ~ the tha ner seh sec [de an< seI• (P• wa of era p3: TIFL 0305544
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508 I 70SEPH D. 3fATARA2Z0 AND GEORGE SASLOW the num er of smokers in both groups was hel constant, this significant differenc still existed. Despi e this greater knowledge and/or nviction in the lung cancer scientist group regarding the health hazard brought on by cigarette smoking tawton and Goldman's next fin ing was that there was not a significa tly greater number of lung cancer ientists who had quit smok- ing in t e period 1952-1957; nor did a signifi ntly greater percentage of them ex ress a dissatisfaction with their s oking habit (25% in one group a d 27% in the other expressed dissatisf ction that they were ciga- rette sm kers). A fin part of their study showed that ex ressed attitude toward lung cancer usation did have a signifi- cant eff ct upon the smoking be- havior the psychologist sample of smokers smoker-psychologists who felt tha smoking is a cause of lung cancer t nded to have a lower current incidenc of smoking (p<.02), at- tempte to cut down the amount of their da ly consumption significantly more (p .01), had a greater number of (uns ccessful) attempts to stop smokin (p<.05), and expressed more di atisfaction with their cur rent s king habit (y <.02). The fact tha there were so few (3 out of 70) lun cancer scientists who felt that s oking does not cause lung cancer nade a similar analysis of these a titudes for this group not meanin ful. However, the fact that, relative to the psychologists, there was no a significantly greater num- ber of uitters in the lung cancer scientis group, with their greater ex- pressed conviction of the health hazard, again emphasizes the im- portanc of noncognitive elements in smo 'ng behavior, and highlights the fac that even for health experts the health hazard per se is not a suffi- cient deterrent to cigarette smoking. Thus, one is not surprised that Ham- mond and Percy (1958) found that only 6.3% of ex-smokers said they quit smoking because of the lung cancer reports. Whatever factors motivate continuance of smoking are thus seen to be more potent than scientifically accepted probability statistics showing a greater health risk. Study of Harvard men. McArthur et al. (1958, pp. 272-273), reasoning from a very small sample of those smokers in their sample who could stop and those smokers who could not break the habit, found some slight suggestions that early breast-feeding habits and later personality integra- [ion seem to be related to ability or inability to quit smoking. Flowever, these findings and those of Bergler (1946, 1953) on the reasons for exces- sive smoking probably will have to be investigated by other measures of "personality integration" in addition to the clinical interview and the Rorschach inkblot technique. DIScVssIDN Table 6 is a summary of the char- acteristics which do, and those which do not, differentiate smokers from nonsmokers. It is clear from the studies just reviewed that our knowl- edge of the personality and psycho- social characteristics of smokers and nonsmokers is only in its beginnings. Nevertheless the studies do suggest some answers to pertinent questions which have been raised in this general area- First, the question of a"smokes s personatity." Inspection of Tables 1 through 5, plus consideration of the other studies reviewed makes clear that while smokers do differ from nonsmokers in a variety of character- i Age Sex Fore Curi Oca mili Frec Urb: gesi cc Incc Soc: Cof. Def Cha m Bod Dd- Par Ta, Psy Psy. Pryr Emc Extr Nun Coff Alco wei{ Dar: Can Smc Edu Owr Part Far istic a si. clu=- plet this su:r coli trut son. Ta Mec nific r.on. TIFL 0305552
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UNDEAWOOD 117 AL. rati g. Ne also found that placental weights w aqual for smoking and nortansoking m bers. Machfnhon er ol. reponed that the differetres in birth weisht batween bab es born to smokcrs and nonamokers in- t:r sed with parity; however, they fnund no diR enea in weight fot these children at I yea of age. Bernhard found a lesser effect on irth weight for hensy smokets than fcr m tinle oncs, postulatinF a tolerance to sm •ing. Herriot rr al. and Underwood er DI. rep rted eontradictory diQerences in birth wel ht when comparing smoking habits and soc' onomic atatus. Yerushalmy*T found no i erease in perinatal mortality with smak•- ing. In evaluating the effet.1 of fatheri smok- .ing abits, MeeMahon er a/. found no effect on Irth wdghi with paternal smoking: bow- eve Yerushatm)•'• found increased prcma- tari p. F om interest stimulated by these reports, a pr spcctive statisticai study was carried out to d termine the effects o( parental smoking on egnancy and its outcome. M4ita14L AND MEIMODl de shects wve submitted from 44 wor wide naval installatioos. They eons'sted of 6 columns of information pertaining to prcg ancy and patental smoking halsits, in a suit b}e form for transfa u data processing n Thcse code sheets were completed by the Dem1"mg physicians upon the mother's adm sion to the labor room. Between luly 1. 1 63, and lune 30. 1965, 48,505 women with single pregnancies were delivered of int ts weighing over S00 gm.; then eatts for the bas6 for this report. When intor- tnat was ineomplete, the case was ex- ehd from statistieal rnnsideration in that persi War groop; thus the number of eases in dttte enr categories varies. Ila smoken were divided into 3 groups: B moderase, and heary smokeesm aaeord- ing the numbcr ot cigarettes srnoked par , sd 1-10, 11-30. and over 30, respea . T1/M1a /. 3~:INn ma,n aLSTYnY ~lri{A1pY Su6,str Nrr C/tarrmr yri cbr O.er t-ro rr-b m Meders Na 2s,e65 T,YA 14A50 1370 % 31.3 13.7 Pa 3.7 Sponsc ot.eenneaine modrrs No. 91 3,/93 t0A03 1,330 $ 31.7 1e.2 41.7 3.4 tively. Approximately half the mothers were smokers, the majority in the moderate group (Table 1). In a preliminary report of this material, it appeared that fathea' smoking habits in11n- encad pregnancy outwnse, as bad been ro ported in the literature by others; however, elose observation o1 the data revealed that an ineraased number of wives smoked when their husbands dso smoked. Tberctme, this evaluation of the effect of fathers srtoiung includes only fathers married to nonssnokine mothers (Table i). There remain 24,674 fatbers,otwhomi smoked. assws The mean birth weights for an gestational ages, according to the smoking hahits of the mothers and tathers, are shewn below, aaM•ra, IM6,.raW pe do) (fm.) Modass Nene 1395 1-f0 3766 11-30 3196 rrwr3o 31e2 FNaen Noae 33% 1-10 3319 11-50 3391 Osa30 3393 The etatistical signigeme of the data penaining to birth weights was established by the She1[e multiple comparison procedure. For a dnfcrcnea between means to be staled 2 -- r~ 4154231 TIFL 0305509
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5,9SS0£0 'IaiS {(H)'> . I }.' w{ I i TCA) '> f"{T P:'C e a-1 T00': 5 Tl 4 -'{' i I I :Gp O] TOL i tacx .ir.p Sryx Jc as7z bodo et;: :n( op q 9r+as i naar.-e.c.nJavmo6w aidoad op aai7o J:oJ{ ' ' {.i~yom.l I ve :Jnuaa:amL us I ....;n , v pva rc:.er.: v:i+sc:,ojv aCna3 iv~:::.u fo aauo[r,vJ $O• i. ._ S6A1n-e~O.C CSt" CJ3):O:TS d0 WII91Y:.:7~2t'8D s E ~._..._.....t+uo.une - 0 i. . . .14 IMMJOM W .. !. . . .. . . J e i Gt. . ' S91 La r~~~ ~ i ~1Lt 71~Oqn SYr•0a ~~~p ~ . ' aa.q ot.9o7 :uo nu6 CQ I JO. ~ .............. Lp~e i 1SOa1 TOL [IOL•at 4{TJnSyQf lno.( ai}q -aae noL piQ T ..........~Ja~A . ......._..c+.~omog !plcc 'Oa p.q no.c qcr,rn ao;tj noL i I Cvr7 Lm coiJo no[ oQ { 5 7 ...........y.j10 8'OL ~ ..............~ti I Zar~aau ao Lr,m,aR~ so6 a,,,. no1 ~aq.a qmJq. jo «an~roq. .cq 4,oq aoaq zAO no asg ~ 9 ;S ' .............. vyJo .......... nw;taucs i f 7.9 { ............ ( I' jSUwr~a ' p~ dv:cp Ss:7 naY: 1t~i1 i yY Yp_~.im5 fiIDt•U JnOn I nq jvpi:/W::YA9 nC.C aJS' ' I N .f . ....... . . V CIJa fJa:T {"IC L".. ----- -iL't:NVCs 1. ~ i~~TTf nx0 JIi~Y pIIjIG ~ T, YdVY.1 114; 01 +-+CJ CDf JH ' nOA IY.i: p~=~ nVS Ct7 • L.........v~ o4a 1 .l ~.. .. . .. . . . c, c ^o:.~ng `, i .... ....tas :c 1autu a
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ot a suffi- smoking. aat Ham- und that said they the lung . factors )king are :nt than ibability r health IcArthur easoning of those zo could :ould not le slight t-feeding integra- .bility or iowever, Bergler or exces- ave to be sures of addition and the he char- se which rs from om the - knowl- psycho- <ers and ;innings. suggest uestions t general smoker's I'ables 1 n of the es clear er from aracter- Fo CIiARACTERISTICS OF SMOKERS AND. NONSMOKERS 509 TABLE 6 Sawaas Axrn Not+saorinu: Stnouxr or D.ra Ravrewac gn-born parents Cu nt marital status; marital history Oc pation, including unemployment Mi tary servioe, curtent or history of Fre ueacy of job changes Urdan-rural residence R In dence, United States coastal versus nom taI clau, including social mobiGty College graduation history Delicate motor coordination cteristia from 20-year study sum- rixed in Table S B y sway suggestibility Dri 'ng accidents P icapation in sports Ta lor anxiety soore Pa hological tension level (CMI) Ps hiatric versus medinl status Pa chosomatie symptoms, number of Em tional status ("oeurotidsm") Ex nvendon-introversion Nu ber of hospitalizations Co ee consumption Alc ol consumption We ght inereax D k adaptadon Ca ttr-scientist versus psychologise-scentut Sm king habits of parents Ed cational level of parents Ow eduration-age concordance Pa ial venus public school attendance P Ucipation in school activities isti~s, none of the studies has shown ngle variable which is found ex- clu 'vely in one group and is com- ple ly absent in the other. While ttii is true for all of the variables su marized in the appropriate col mn in Table 6, it is especially tru for the variables measuring per- so ality characteristics. Thus, while Ta lor anxiety score, and Cornell M ical (psychiatric) Index, etc. sig- ni antly differentiate smokers from no smokers, the mean differences are I Nondi6ereotiating Characteristics Race, United States white versus United States nonwhite Hollingshead fndea of Socioetonomic Status Education, highest grade attained IQ Mental and motor functioning, immediate ef- fects upon not large. Examination of the means, standard deviations, ranges, percent- ages, etc. of the various published studies makes clear that while group trends suggest the smoker to be more "neurotic," on the average, there are still many individual smokers with neuroticism, or anxiety, etc. scores lower than those of many nonsmok- ers, and vice versa. Thus a clear-cut smoker's personality has not emerged from the results so far published in the literature. This is not surprising TIFL 0305553
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C2tARACTERISTICS OF SMOKERS AND NONSMOKERS 511 smoken and Six pain, differences in n one smoke smokee rigars .e pairs, less show distinct moker and a Id a cigarette c pairs only alike, while Iistinctly dif- gainst 24 per ; several ways h attention is the smoking : monozygotic J fewer diver- ioubt that the le influence on .lar habit of :tudy of twins is competent aidenbk dif. ween the dif- :hemselves as it classes of the other hypothesis maybesome in both lung oke cigarettes. wever, if it is ina cigarette lerably in the :actor of this ridely spread ~ many coun- This seems a ~d imaginatior. :ivable mutual ne has yet pre- t of them.... sex dlfference, time trends in rette consump- ausal hypoth- nce all point- I no evidence .n, I can only i my opinion, factor in the 0). I,4 is clear from his remarks that ammond is as skeptical of the evi- nce suggesting a hereditary predis- osition to the desire to smoke as he i~ to an alleged hereditary predisposi- on to lung cancer. However, in fairness to the genetic ypothesis, it should be pointed out at the possibility exists of a con- s nt frequency of genetic predisposi- t on combined with a progressive in- c ease and availability of cigarettes uring the past 50 years. In short, an i~teracting, ecological relationship c uld exist between genetic make-up nd culturally determined economic c nditions (mass production, market- i g, etc.). A third question that deserves con- s~deration is the possibility that s~noking behavior is determined by u2liple factors rather than by a s~ngle factor (personality or geno- pe). Table 6 suggests that for any ven individual, his smoking be- avior may be socioculturally deter- ned, age-sex linked, related to oc- cupation, and/or associated with a ariety of personality and other be• avioral characteristics. The present eagre available evidence does not ermit the determination of the rele- t weight of these pertinent factors s~gly. Nor are there studies which s ow the multiple correlation with s oking across individuals, or within single individual, of the various aracteristics shown in Table 6. In addition to these uncertainties, should be added that none of the studies here reviewed provides an nswer to the "cause and effect" uestion in the relationship between ychological characteristics and s~noking behavior. It will be clear to tlte reader that the studies just re- iewed showing, for example, slightly ore "anxiety" or higher "neurotic dices" in smokers compared to non- smokers were merely studies of a re- latioaship between smoking and these personality variables, since in no way were the studies designed to investi- gate cause and effect. There could be a complex mutually causative rela- tionship between smoking and the various characteristics shown in Table 6 (as well as smoking and lung cancer and/or coronary heart dis- ease). As Hammond (1958) points out, at this stage of our knowledge, for example, there is as much enson to suppose that ciga• rette smoking causes nervous tension as to beGeve that nervous tension nuses cigarette smoking. Perhaps they are mutually musa- tive as in an autocatalytic type of reaction (p. 352). A similar statement regarding cause and effect could be made about each of the many other characteristics re- lated to smoking shown in Table 6. Longitudinal studies of youngsters before and after they have begun to smoke might provide some leads to a partial answer to the "cause versus effect" question. One such study might employ an anxiety question- naire and could provide information as to whether nonsmoking youngsters with higher anxiety scores begin to or do not begin to smoke in greater per- centages at a given age than do youngsters with lower anxiety scores. In addition, readministration of such an anxiety test several years later would permit study of the question whether or not youngsters who take up smoking later earn higher anxiety scores than control youngsters who have never taken up smoking: or earn higher anxiety scores relative to their own presmoking anxiety scores. Numerous other designs could supply additional information regarding cause, effect, and mutual interaction. In summary one can suggest that, while this review and the data sum- f J TIFL 0305555 ~
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csA^_.r-=^_szca OF ::.:o:Zrs :.xa sua:cur.sa= T. 237 45 L-Tfap]nar (mn?Or..nr. Lf ,•,!I:1~}n{ ,)r0p{'a 4( p~ f./.![i Rry. i.Yfa cr.C senar...:v.r in pa;:ennuoirr r•v ~.-::{•.::a! r~:r~w•-t;oa[iou•d ' Cli ' . n ,.:r... QI:NIlN[[ Cll':'• : ~J:Y 'TAfvtL ' • .r.a:.• . J.~rar P c[[c ,mn s.•: .. . ~.CAXa•a~ . ahrCa. I .... sourr:rru;a[ AImw:nt•.•t:..... 5nsctum•i..... ... .. Ycrv ufh~u......... I 21 Haer z.e[ nmr 1•sd aq' ~ 41 5 [: 7 fl. _..I S a.: ~ I i ~ (4intin~ s;+e[[aT - i , \nrrr.....•...... .: ;GS! : ~=b'= I -x[1{'i: Lp 'J4mrtimr..........i rG= u6..•. ~ OTmn .............. : ]t t ac { r ~ 22 Do rnu bita your anqna+ t na+7. nW f \c.ror ..............i Sctue:!mey... . UftcR .............. '_ I - i r ~ t r 2$ Hatro -ou enr h.<o ; be,ehrwd by prrmums Io ; tbu headT i \evcr.......... A (os timo.........~ , - Oftsn ..............1 An pou nver troubled / [ ritb yinL h..nJytS1a' ' . Worrr.•...........-1 SL D . ' .O./I $o[nrtitrxl. : .. Ofam ...... .......~ 3.3 310. wuuul .nu .n}' pw. i 2rou l•ncv faet ab..[t I ~ u . N[ROtt aU I!Yar :ae... ~ i.. I . Jfmtof thcm likn enr.. aa n A fe[v like me....... 1 •• 7. - Altrwt nonu Iike mu.1 0.2 2Q. Do yC[[ NLrry W'rY IAOfJ •lout thinp thnt miSht IyDp~u W ywT bot ni a3L.......... Nhsu ~eo *ete rro.tug' up, dtd 7nu hurr .nT eroudlo xtth sluteM ia' ~ . . .N ~a .............. 7^_ 2 D3. 2 Bome[itou.... ... fl a . S. 7 ~-~ Ohm ......:.......i L&, . LI ,J Y-0.Ia. 5- i 1Hwor lYfe T0020g94 . I TIFL 0305566
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CHARACTERISTICS OF SMOKERS AND NONSMOKERS 513 I stud- rs sug- e next ;reater entists luman =. Ex• i, Sept, smoken intern. .Ith and ntal in- ,.J. A. uxpiora- v York: Sociaf : York: 2.M.,& g among 51. Hltk., 74-7 , (Repeinted: Ca: BvU. Cancer Progr s, 1958, 8, 49-52.) LzNN, . M. A study of smokers and non- amok as related to achievement and va ' personal eharaaeristits. U. NC Ree. s. Progress, 1948, No. 464, 164. (G . Seh. Series No. 56) (Absaract) MeA¢ 00. C., WAt.uaoN, tu.aN, & DteuN- soN, . The psychology of smoldng. J. abn a. sac. Psyckol., 1958, $6, 267-275. MATA o, J. D., Guzs, S., & MArARAgzo, R G. An approach to the validity of the ylor uuiety scale: Scores of inedical and chfatrfc patients. J. abnarm. soc. Pryc 1., 1955, 31, 276-280. MATA o, Rtrte G., MAiAttAUO, J. D., SASL, w, G., & Punztrs, JaANrs S. Psy- cholo 'cal test and organismic correlates of in 'ew interaction patterns. J. abnorm. soc. ryclal., 1958, S6, 329-338. Noara ar, E. Scienu looks at smoking: A nrw nguiry ixto tke effeds of rmuking on yocr . New York: Coward-McCann, 1957. PeANts vf, R. A. Causes of smoking. J. -Edac Psyckol., Baroda, 1951, 9, 29-37. RwvEN, R W. Smoking habits of schoolboys. Lan 1, 1957, June, 1139-1141. Russ, Smoking and its effects. New York: lan, 1956. SAC®1N, S. M., & Coxovsa, A. G. 'Ibbacco smoking in the U. S. in relation to income. USDA Markalt res. Rep., 1957, No. 199. SASww, G., CauNn, R. M., & Dv Bots, P. H. Evaluation of a new psychiatric scesning test. Psychosom. Med., 1951, 13, 242-253. SCaosaxx, D. S. P. Personality impGcations of cigarette smoking among cnllege stu- dents. J. constrlt. Psychol., 1959, 23, 376. SSODI GAOVe oN S1fOAING ANn HeALrs. Smoking and health: Joint report of the Study Group on Smoking and Health. Sciesu, 1957, 125, 1129-1133. SutEn, D. E. Appraising uttotiowl j~hssss by means of psyckofogicnl tests. New York: Harper, 1949, TAnon, JANer A. A personality scale of manifest anxiety. J. abnorm. soc. Psychoi., 1953.48, 285-290. Twnoa, Jwxst A., & Sraxec, K W. The relationship of anxiety level to performance in serial learning. J. ezp. Psyr$oE., 1952, 44, 61-64. Tteoesser-, R. G., Dwvv, R. T., & HENnt.ax, C. D. Dark adaptation as a function of caReine and nicotine administration. Prac. S. Dak. Acad. Sci., 1951, 3D, 79-84. VAttr.Nes, T. R. Suggestibility of smokers and nonsmokera. PsychaL Rec., 1940-45, 4-5, 138-144. smoking Psyclni. 50). a of the n presaM phed re- State of Smok- Texas. -299. :igarette iology of 1958, 13, The rela- te smok- 4mer. .7. id other smokers pidernio- nd other 1959, 22, ing: Fear 757, 200, Rtixs N, D. D. An open ktter to Dr. Ch ct Cook Little. Athntic, 1957, 200, 41-4 .(Reprinted: Ca: Bali. Cancar Prog- ssss, 958, 8, 46-08.) (Received June 17, 1959) TIFL 0305557
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nsistently e of non- a 31 items nce: 11 at s, 4 at the and 3 at direction :ems were 278) was a signif- xpitaliza- chor sug- ss number ct neurot- ect other en disease Lilienfeld nalysis of :alizations eld, while .ndings of our own, additional was large adequate re normal city; (b) o groups variables i status); check on cwo other ubgroups ty under- psychiat- : medical patients), .th a non- _dult nor- esentative ilts in the the other e fact that the other ing. .ent is in ortcoming re studies CXARACTERTSTICS OF SMOKERS AND NONSMOKERS 503 and several of the others here being reviewed: The differences between smokers and nonsmokers were based on self-report. While it is probably true that smokers and nonsmokers have similar "test-taking attitudes; " there is always the possibility that the "response-set" of the two groups differs in such a way that smokers have a lower threshold for admitting "neurotic" items than do nonsmokers. No study suggesting such a poasibil- ity is known to us. ~ On the other hand, there are sufficient (neurotic) indices not based on self-response questionnaires which significantly differentiated the two groups (e.g., Lawton and Phillips' finding of a greater incidence of Heavy Smokers in their psychiatric sample in con- trast to their nonpsychiatric control sample) that, in the absence of data suggesting otherwise, it can be pre- surned that smokers and nonsmokers have similar test-taking attitudes, and that the obtained differences re- flect significant differences between the two groups. Even if it were shown that test-taking attitudes mere different, this fact, by itself, would still be an important psychological difference between smokers and non- smokers. Psyehosomdu sc.cening inventory scores and cigaretie smoking. Table 4 contains for the three popula- tions studied by us mean scores for smokers and nonsmokers on the Saslow Psychosomatic Screening In- ventory (Gleser & Ulett, 1952; Saslow, Counts, & DuBois, 1951). This test requires the respondent to check from a list of 23 symptoms (dealing with bodily and mood dysfunction) the particular symp- toms he or she experiences in every- day anxiety and anger situations. In all three populations studied, the smokers report a greater number of psychosomatic symptoms than do nonsmokers. While these differences reach statistical significance only in the student nurse group, the trend is obviously in the same direction with the two other samples. Cqfee.and alcohol consumption and cigarette smoking. In our own three groups, coffee intake was scored as number of cups consumed per day, while alcohol intake was estimated on a weekly basis by a crude scale that gave differing weights to beer, wine, and whiskey. A score of 0 was given to nondrinkers while a score of 5 was assigned to 21 or more glasses of beer per week, or 21 or more glasses of wine, or 21 or more single shots of whiskey. The results shown in Table 4 are all in the same direction, and reach statistical significance (p<.001) in two of the four comparisons for coffee consumption. Thus, smokers con- sume more coffee. For liquor, again the trend is in the same direction for all groups, and the differences reach statistical significance (p<.0o1 and .05) in two of the four comparisons. Smokers also consume more alcohol. Both these findings (p<.01) have been reported independently by b4c- Arthur et al. (1958; p. 269) and Heath (1958, p. 385). An interesting observation in the literature on the possible interaction between coffee and cigarette intake is that by Troemel, Davis, and Hendley (1951). Studying a phenom- enon (dark adaptation), long of in- terest to experimental psychologists, these authors report an increased speed of dark adaptation after in- haling cigarette smoke, which could be counteracted by the simultaneous intake of caffeine in a small dose but not by a larger dose of caffeine. Little systematic research has ap- peared describing the relationship between food intake and smoking. However, smokers occasionally re-
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A. N. A. dRCXlYES OF tN7&SNAL .MBDfCiNB rial wmparfsons with other factors were but have not cevealed consistent relatiutt- shn with smo)dttg. Some of thpa are li d a•s fnOnws; . W}iaht od vdprb ratnnR ber see sevuilr ct IHU ;Itumu , of ARa&Yvilshs dunng cetiq{e ueeq ot meuaoa eddf metabdism Icbfn 6tnyt: dandca of nm' lcaf atness: eaoaveeY hda." ry Satess: lanie sod sft.r tua rrta COS. MS, 115) sr rate (emeking iu mtlrge) toliu6/ced laaore ' 064 bioed prmme of teetk fl0ed or spaaeg of IwfY re of Nte P 1170 010 Q41 ¢19 arr 0.3c a57 0.80 0.1z 0.6{ 0.'0 027 O.R 0.1Y 0.ne axt 031 aa 0.{S 027 0.96 ffroy 0.H1 A rating vf the uumher of sldn moles. de: during the medf®t eaamination, coo- ed atrprfsittgly with the OS. MS, HS egories (Pr!0.01) (Tabke 10). An exees ncrnm0ltets had onfy' rare body moles te 10, hwrerey is not consistent, aod is fdt tMt this may be an Cnstance of (Slnee: there its 1 chance in 100 P eqWtmg 0.01, it is to be rxpeeecd d.mee eloee will account for such a oosbip whee smny coemparisaos are ) However, ft ia conceivable tlmt nmle may be rdrted to tumors of'the' hatory epitM)fwn, which is also drrfvcd cc0.crferrn. Suoumry, and Conclusions Two hundred fifty•nvo sdected colfcge men, fint studfed in 1938 to 1942 and fol- lowed by intervietv and qtkstionnaim since that time, have served as subjem for an investigation of possible d.Rcreucee in persoimlity and physiology between amnken and nonsmuken. The collection of data on ssooking was & pact of a much hrger ml- teetfon of Cttfeamufert fran the sabjects and waL neeer stressed. After observation of individual sosokiug habits. iwer the years, a division of men according to smoking ImbCts was aa folkwrs: 61 nmumoken (242%), 93 moderate smknrs (37,i'ye), and 96 hcavier tnenkers (J8.196). Aentnparfxat of the aase records of the 6ve hcsviest rnmkers (two or mure lwckages of cigarettes dailT) with. those of 6w uott- snwkurs choaen at random showed marked contr,uts in pcrsonalitics. Thee smokers showed great energy, rcseleasness, seeking for d.itsgee, and a kind of inderendenm which keeps utem v.tively mgxged in same entwprire which aypenft, utd they had Aifficultip with marri;tge. The nonsmokers werv aeady, dependable, and hard worken, with stable marriagm and histories of ry,ninlised, uoncomfut war dutics, and.they, led rather quiet progressive lives. Sttdt dif[erences were statistically bnmc out for the whole grottp when canparsfacs ~e made with certain personality tnib tlstt hud already beem ®tegoefzed aml with uther di4. which distinguish porsons from one atsuthax The twnwrokas, as a group, Iwsstsx the more slable qualities of depend- ability and good Aircetion of aims in life, althnugh they are somewhat on the bland tmcunummieaHve side. The group of smokers appeara to wntain moru oC thc men wlru are energetic, searchutg for aima and '.uut tR-Ne~~E ~'~~+ Rrkrad ra purposes, verbal. variable, aml perhaps, al- ~ though Rsa stable, nwru intcrtyting. The nonamokers lend,.d to major in natural uw t~ .~ . sciences, particularly physics and chemistry, a s q 1a.t~ while in college; the smoktrs tcndcd to ~ p w p dmnv: mtjon in soci:J studies aml art.e and letters. The noaunwken tended to enter T075909 YeL lOt, FeA,19Sd WIA1 0000627 0305533 ,. _
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7. Are you over Irau6lcJ by your Aouds nsnwllng u ley c r p noJ elswuq9 . 52.1 13.79 <. 001 0.80 6: 1'>. 3 aa 6 1. 13 3>)'>.2 . B. 116" pou ever Leeo LotAcmd by tlloftuna ol r. Ilreillr wheu you were lO K4rk- OUt OY 1 o }1 > en ` 1 r 61p hpnlt a0. 2 13.73 <, 001 O/.a 10.69 .01 57. 9 G 74 ~.01 i n 1 0 0. Do )'YII Y/I4n My L111/1p )rou lotrr u1.4 yuu IwA 1 j ' no) e111J1 64.9 12.3 <. O(/1 52 U 1.09 .30 51. 1 I. 49 _ .20 ~ 10. Illd yw cvar Wlo yaur Oltliurunlle wl/cu ywl N'lYY 11 e1/il.l7 51. 0 11.7 < 001 SA 1 0. 111 711 111. 0 LL70 5?/y.lt 9 11. 11n )'.m rr.rl pw w1 IAnr . nnrl /I/aruurnpeA tlnl )1i11 4~MMI/'r UI4'III('1 suyWinl~ e+ 4•IrILw646:' Il'. 4 11, 111 C. fYll J . 1 /. is 115 3s. 7 5. 111 12. Aro v.nl ev.•r .ar•rrir+l nn/l ripa.17 U. IOL ;.01 I. fi(1 211 W1 I G.A9 <. U': 13. Ilset• yno rcnr W.,n aoubb•J 6y '•rnlJ b 0 \r Iar4al? '7 00.7 B.UI <.UI ' OY.6 I O.IN GU 01.I R. _•i .e 1•1, 11s1w' p.w ever 6oJ ryralls ol dirrNT 6U. 0 7.74 <.01 57. 1 j 048 ` 50 {6,0 1.67 ` .7/'>.1 O 15. llo Z-ou 11•d you Fot Inorc LLnu your s6nre of LIIJ lurk7 40. 6 7.011 1 <. 01 61. 0 i 1. 47 .3>/'>.2 43. U 2,81 I . IO;+Pj.05 ~ I ~ 10. llcva )•ou evrr lrccn LnlLorcll by rnn. LuuL Le.ainU Imol'1 51.3 5. OU i. 0'1 '1- )'>. 01 bs, 1 I a U;t I .61Yj.3 /2.9 ( 1.51 ~ .90 H H hd r 0 w 0 tn tn ~ 0
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278 Ycrvshal Tab'c 1. Peri Y by mothcr's. *uol:fng stmus in 4 Inrgn studies Per emt Icx~birrA- •tiihf ie/enls (S~ ff0 rrsl n r 7nrrdifnMr 1 Prnr ,Yn of - tr Undrmoad sn omodurs°o 1967 +8,5I1.i s.7 Raotakaliiu°[ 1969 11,931 3.3 Brnler and euil agucssr 19u9 t6,994 3.4 1•ctwhalmr's 1971 11•hite 9,793 3.2 Black 4,?90 7.8 -Yrnulubnr r an w iw..,.r,t dmrh mlr. tality rate, if uch an inercue really a<istccf, is ccry srnnll p < 0.001 (35 pes ecut sras ttsed in tite alcuL•ttien becune an iscrcasc of this magLudc is czpccted from a nro- fold incrnsc in 9m incidence of low+birdt- tccight infan ). Tutc 4 stu ics trhich sccrz based on rcla- titrly large amples consist of the follow- ing: a study y Cndcnwod and asaciattn° bnserl on se e 483000 prcgnancics of dc- pendents af tatml Pcrsonnel obtained from 44 t+'orlchcid rmrtl installatioat, a study by 1Lntakullio"s on seme 12,000 tases repre- unting ncarl - nll ptagnancics in tttro psnv- inces in nont ern Fl:dand, a study hy I3utkr and colleagu s'r lxased on some 17,000 preg- nancirs rcp tung all the births which oecurrcd dur ng ena week in England and 'k1'alr.r, and study by Yemsltahn3's based on nearly 10. 0 st'6itc and over 3,000 black gnci<Lu.rcp ting all prc;uancics in a si.-yenr peri in the I:aiscr Hospital in Oakland, Ca •fornLi. ButkMs study was ret- rospectiNe, t other 9 large studies vere prospectiYe. f1 dte 1ar;o-uale studies w'itlt the e\ceptim of llutlr:r's found no escca in Ixrilzuu nto tality rate for {nGutts of smok- biq nsotlsets Tahle S). Cndesssvo and aasneiatcs' nnd Rnntakal- lio's data rclt tc lo pcrinatnl monality nstc-- lattt fctal mn neonatal deaths. Yenlslsalmy's studicts cnns dcn•rl only neonatal dt•aths. ilau'cvcr, T3 ylur's imxstigatcd fetal doath in thu rlala f o111 tilU l:IItIC ttudlZY arltl A,Itttl tLat thl•. tik of fr:txl doadt iu carIt nlnath of Pt'cgnancy is af tho suun order of nl:rGai- t11dC for stllO lct's Iltld nnuenwkcrs (L°ig. 1). Q too t 0 Jems<y Is. 19R t»,...r. crK,d. Perfrtnb7 Jrntbr Der 1A00 i'omf <a,iao cr,onr 19.7 '+1.8 ^-a9.0 107A ^-9 = 23.4 149.G '87.6 32.4 {4.8 281.i ^.GBS 11.0 11.3 210.3 IIS.9 17.1 ?1.5 201.6 It1.6. : 7o u G.ttelien cav. lvnm mamh. Fip. 1. ProbabilA7 of fetal dcath In srcdAcd month of prc,±r.onry and all fubuqvcat manthr occordinS to smokin8 nuus of white ;raridu (Pe..m Tatiorq W. F.ssJ. The Itandosical plsenonsenan of an in- crease in the proportion of lmr-birth-%cight infalte Withaut :rn incrcasc in I>.:rinatal snor- tnlity mtc is csPl>incrl bp tlta intcremting fsuding that lotr-birlh-mcight infants of nnokin, motltrrs have utnch loscer peritcital rnortalitp ratcs than luw-birtlt-arriylrt infants of nonnnokiug mctltcn. Tbis waa found in all tlm Lvgc-sc:da prospcctice atudics m may be sccn in Table I.. . grnm a retimv of nll lhe cVidcncc, it is, thcrcfnre. Ikri~,ilde to concludc ttith [onfr- drocc dud: (1) a sulsstarLLiaily Iar3cr pro- pnrtian of inGurts of >makiug Ihnn of unn- e[uukiuG umtlsts '.tn of lotr birth .rciylsq TIMN 254625 20 alnl dcatln* among all infants and among loa•-birtlt-svcig.ht infants 6.9 6.1 9.3 birthr S~.nvnNVrlSnm4ri .CnunntrrlSmnhn .\'onnrt.•lerlSrroker t t TIFL 0305517
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1' . ~I T.yLF 4^CN'IpqrMY1F YI rrfpxNNi IN'nlIMN49rr11 NI RMOIIOHnI fIYIN1 J!! InIyFMMCFfJ yrONP ' 4yYrllkYNp..l,u mld nannvYt•r., fur MYk DrrssYi ' i . . . , „ . . odu, and far Amlry.wuler. N.dy Q H H ~ r 0 w 0 Ln tn 01 to y t wnnl 4 A Ixn • o t / . 3. Il/f xl.ur Lund. rvn • . -Ir 1}IIrnM11gh1u1Nx6.r j . Pmlf . ,. ..: . . 4, sm 711u 1o111.rqA by ~ , fn . 11t}1'U11WNW, ,'1 .: - ~ ~ ~ rV P .S.IlOW, aIYN dn pwld.• C ' g 1tr1 na 1u11r uxrVrY w. (JI t IIMt 1'ou tiaut lo du Ju,{ ~ 1. l1n ),w •vl•r lrel lic M ymi.l,iuM IId1Wtl 1cr } RYY11 I,nNMIt , . :. 1/nu~ u/lrn'luar II qmk" Y/NI Wnn Ix I~Y.vI po,id': € Illeulq.r•dlaufwlutllnq p { ..0, I)O p nl 11.14 tbnl 7nY 1 n11eu Ln/e la ICII proplu ~ln nl!nd Id-ir 4M'4 bOaj- iulnlgruql . }lainl uul;• _ . _. ~ . Perrr ul uf ul},r I IN Y"I/{CF 1 Y(Y . n41x'1,~'! fn n$4•b w f!d yl.ro I flqlra/1C ' 4' - !r. [IF•IrMll: } d 1' NnwYYr. y. . nnnkw. ^ ~ ryrl~ ' j antl IY.IIOIII„1.[[ .~ I MJ .. . Illl IMIM11n~:aI1 y 1r:0.1 d41N /IJ 4 !. aY1fC/1 . . YCM•..1 ''1 I 60.'Ir LI,3 i •';.uul 7 1. !1 I 5. 97 ~ -..U': I •189 74: ! <,00! ~al.U I 3.0s l .u r•t?.Oc I ~ 1 1 1 . T•:.3 -0.:4Y I <.Oot , 41.6 ' : {.36 1 .L LL1 . •~ ,{{. 11 IR6u i - •:.Ix1t. . l i, 19 1 <.6oi •17, 2 1{.5 1 I 1 <. Iw r, /A ~ i 1 q 5N ' . <. 02 - IIw1T . ~ . . 1 ' {5, 6 Ilr.n~y nlnnA,•rs Pvrcrul uf I I n6/1MIM'i I l'll! ir/uGiall e,,r.Mr ~ rilb'ralr f 1 I prr' I' xu.4oro nd d1/NI~ I I~.al~llx~l:,•rn '.KI, 'd ( . . ., ... . _ __. .. .._ I.. . I . d:LU i LSNi 1 {s :, lu Inn I 67• 0 111. 7 . . !• IS!1 n,U+ {7.5 S. 01 i <. OS 61.0 : x:a I r .r>.1
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_ ... . _ . _ . _ . . . . a--~ , as7~~ yn~ ~ ~~ :fass~ .i4g- is: of infant other's cigarette smoking and survival a•r~dry, C.4/.ni. YERUS1fAL1tY, Pu.D. A. t w a a nf recent invmtigatinns Iwve aonhmavi t original obtervationt made by Simltvn in 1957 that mothen who snwke during pr naary have a much larg'r pro- portion nf thcir bfrtht in tlte "low bath weight" gr p(2,300 gr+tns or less) than methen o do not smeka."r It u wcll knewn Uta infants of "low binh wcight" experitucu very high neonatal moruJity, ru<s. 'I'hw Shapiro, in a study based an over 800.J births, records a aeanatal mor- taiit,v raao of 173.7 Cor infanta weighing 2,500 gnt or less at birth and 7.8 for in- faota with 'reh weighu of 2,50f grams or more.' '7hc lnrge esersa of infmtu of "low binh ~.xigl t^ should dwrvfora Le aceom- panied by sltbstantial itutease in the ncvl-,_ natal mor iq rate of infants of smoking - mothcn. S att mwr however, iw not b~ron d mtntstra,ted TM ftudip found, ,; at best. not 'nnafl diRerence in ttaenanl' mortality, d ehett wpe not ststbefeatly tiymiHetnt. SaW! aad Roth' ttate: 'Betal wastagq ' bireh; and aeonad deatlv mem s unin by the emoking ha6iu of the - mothen." aompebon.ive atudy ef Yrat`6 tier and asse tommeau: "Although the tuona death- ran, for infaab of Y. tA. CoeNrafr SAh al ChY! D.fe'wot n/ du O:.inn ef __ !h une7 of C' e.:14 l..k.1T1 tM: r« nrr Al.t7w Gry~f .n ta. O A C RasiareA l+Ml " aiitwo T8 , .a rr u.MnN i~. C. : Nrw~ ~ .ef fAi NMiwf nnnken t27.5 per 1,000 live hirtlui u Creatar than the rate for the nonsmoker qronp (23.3 per I,IIEO 6ve births), he d{i- ferenee is nnt signi8eant." This failure tc flnd tutatantial ineteaxa in neonaul mnr. tality in infants of snwking mothers cannot c.vily be explained and calls for mere coln- prchrnsive itrvestigationr of the observed aaoclatloa between mother i emaking hebht and the birth weight of their infantx At the very leue it is detirabk m expand the invntiaation to encompass the :hroe fatton: birth weight, length of gestation, and zurvival of ittfant. Such an investigation is neernary not only for providing a wunder basis for advice to the gnvida wncerning amnking during gragoancy, but also for whatper.light it might throw on the more generaf question of the validity of interring causal mlationshipe from observed attaria- tiats. The purpose of ttiia paper is to present the results of Lt- inoett7{.'atfon of the outcome of pregnancy of stttakin6 and nonsmoking gnvidat with respeet to birth weight, kngth of ;eaation, and nuvival d infant It is, of taanq nesestary m expand the studies in scope te allow for the invatigation of many other variablc in an attompt to undeataad . the complex phasomWm of the relationship of nmking m heafth. Such expanded sttsdies, which inelude sterh teoton at length and hral cin'umfnreneo of the infant at b-vth, nw.uw•Js :.e oha and prepropnaney weigh4 F,ain in .,vght dur{l pregnaaoty, and Caiwr's rnul habitt are tmw ia pngteo and wdi be reported in ftttun pub0eadwt. 05 . TIMN 0072108 '' TIFL 0305502
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506 JOSEPH D. MATARAZZO AND GEORGE SASLOW were re uested to try to be true to facts as far as possible. The results of this s udy were as follows. Initi ion of smoking: the reasons checked for the beginning of the smokin habit are diverse and varied, althoug the most frequently stated reason i a curiosity as to the nature of pleas re afforded by smoking. The most fr quent reasons for beginning and the percentage of the students listing e ch were as follows: I wan to see what sort of pleuure I would get out of it (75%). I thoug t there was nothing wrong in doing so (52%). I thoug t it would help me sit up during nights for study (50%). I thoug t there must be something attnc- tive abou it because so many people do so (48%). I thoug)tt that a trial would cost nothing (4a%a). Two of Ithe reasons with the lowest frequenq'dies were: • I was pted by the advertisements (4%). I wan[ to rebel against the authority of my paren ane amoamg is one ot the ways of doing (4%). Conli ua0ion of smoking: the rea- sons ch ked why smoking is con- tinued em to have a strong psycho- logical asis, especially involving re- duction of anxiety, tension, and lonelin s. The most important stated r asons why these 48 students continu d to smoke and the per- ceatage were as follows: It wv as a companion when I am alone (75%). It warq4a-me up when I am cold (71%). It help~ to forget my worries and anxieties (60%)- It fac itates thinking and gives inspira- tion (32 ). It m me to acquire new friends easily (44%). The lowest frequency reason given for con~t~tnuing to smoke was: To gt up would be a submission to orthod (4%). Despite the few subjects studied, Phanishayis results suggest (1951, p. 36) that the causes which prompt a person to nke to the habit (curiosity, especially) are diffennt from those which are responsible for its con- tinuation (tension-reduction capabilities, es- pecially). There is every reason to expect that the several expected reports from the sample of 22,000 high school students of Horn et al. will yield re- sults for beginning the habit similar to Phanishayi's, in addition to others which Horn's different methodology may unearth. As a matter of fact, unpublished findings in the longer report of Schubert (1959) of 226 northeastern United States college students indicates that the reasons given by these students for beginning to smoke were not too unlike those of Phanishayi s sample. Schubert (1959) also found that for both his male and female subjects three scales of the MMPI (Ma, Hy, and Pd) differentiated smokers and nonsmok- ers. As to the reason for excessive smok- ing once the habit has begun, Berg- ler (1946, 1953), on the basis of five cases of compulsive smokers who un- derwent psychoanalysis, suggests In all cases, a similar neurotic substructure was found: These patients represented a spe- cific type of masochirt who unconrcruusly wanted constantly to be reftued. To counter- act the inner reproach stemming from their inner conscience, which objected to the wish to be refused, they "[uo`+ed" that they wanted the opposite-to get. The outward sign was getting a cigarette, an oral "paci- fier;' reminding the individual of his first reassurance in life (1946, p. 320). FACTORS INFLUENCING THE TER- ffiINATION OF SMOBING How many people quit smoking once they start is not yet well-known. Recent studies (Haenszel, et a1.,1956, p. 24; Hammond & Percy, 1958, p. 295 20 i rece (19: F IOF low. 0, tekf who habi smdW the cenm cg2 alir wac (70 c saic rep adr up eff< oci reg up ug: duf wo: sco: smc me: ~ tes: (al su: 24 wE P iu TIFL 0305550
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/ PHYSICIANS' ATT{TUDES TOWARD THEIR INVOLVEMENT 181 hand, for pregna. , the proportion was 3i per reasons,or because of pressure from professional centt and for nerv umess, loss of appetite, insom- colleagues. Of those who quit, 37 per cent had nia, it was J6 per t; both proportions were about smoked cigarettes for 20 years or more. . the,same as for as ptomatic patients. (All physi- Many of the physicians who are StAI smoking cisns did not answe the question for all conditions cigarettes are not satisfied with their smoking be- because, uaderstan ly, all physicians do not treat havior. More than half say they have made a ser- all cnnditions. Per tages are based on the number fous attempt to stop smoking cigarettes entirely, atiswering fn each e. ) This is reflected in the ac- When asked what they would like to be doing tian of various sub oups of physicians. Obstetri- next year at this time, 52 per cent say they would : oaae, foi exampk, moro likely to warrs pregnmt like. no longer to be smoking cigarettes, another women than are p ioans hs general practice (49 14 per cent say theywould- like to be smoking pei osut vs. 38 per t). However, of these physi- fewer cigarettes than now. These physicians con- cians specb~liaag 1n obstetrics and gynecology, only stitute a gmup, of long-time smokers. 63 per cent 28•per oent.advise eir patients who have no con- having smoked for 20 years or more, and only 3 dition related to king to change their smoking per cent less than fsve years. - habits, whik: 5e per cent of those in iateraal medi- cine and 37 per ce t of those in general pnctice rnsummarymea: advise all or almos all of their patients to do so. . 1) the general public expects the physician to I -Although.84 per at of the general public think take an active role in convincing them that they people will not qui smoking until the doctor tells should stop ssmking and in helping them to do so; them to, 77 per t of the physicFans think that 2) the physicians' attitudes show that they accept "most patients will not give up smoking even if - this role as appropriate; 3) in actual practice, how- theirr physician-te them to." This large propor- ever, physfcians apparently Eall far short of com- tionindioate.s that at least some physicians are pletelyfulfillingtkis,goaL giving advicewhil being doubtful about the re- For patients with conditions which demand bn- sults; others. may e ress this attitude as an escuse mediate action, physicians see themselves as having . for not givmgad ' . : responsibility to change smoking behavior aod at- When VJGen asked wh t methods they have tied in tempt to tuiSll this responsibiiity. About 90 per cent order to assist patle ts to stop smoking, a majority give advice about smoking to their patfents who of physicians said ne or more of the following: have already contracted a disease or have a con- inform them of fu - health risks, urge use of will dition related to smoking. power,• and relate oking to thets current cotuff- In contnst, however, when dealing with the tieri: Only about o in ten indicates that they asy'mptomatfe patient and in taking an a primarily preyentlve role, physicians do not preach what recommenddrvgs help patients change their smoking~behaviorg o of three say that there is no they, as fo the case of their own cigarette-smoking method available ay to really help a cigarette behavior, actually do practice. While prevention smoker who wants qedt, but who mnnot do it was the main reason for the strildng curtailment on his own. Thepes imism about their effectiveaess of cigarette smoking among their own profession, and lack of con8d nce in adequacy of methods only 38 per cent take on this preventive medicine availabfe~may.be e reason why more physicians responsibility witti,regard- to their ownagaretts do not advise more atiertts to give up smoking. smoking patients. ' . . ' - Whit have ph themselves done about 4. One of the reasons for thu may be found in their ownsmokmg viorP Of all physicians who the pesaimismexptesssed by physicians as to their have smoked some ' or another, more than half capability to change the smoking habits of ihev have quft:-When es why they stopped smoking, - patien ~ md this in turn maybe a function of their vtore (60 per cent checked "Protect my future . expressed dissatisfaction with the ef&acy of ineth- .bealth' than any o er category. T'be next most ods curreudy availab-3e. - frequentresponses ere in tbe' categories 'occur- . This suggests that: (a) more reearch is needed renro of certain ptoms" (47 per cent) and to develop effective cessation methods, particularly "sdenti8o: ceporo vfnoed me" (43 par cent), as related to use by physicians worl,dng with thcir . Abotst one in four-checked "self-&sciplfne• and . pitients, but (b) it also suggests that'regardless of about one'in S4e, cked "set a good 'esample their belieF about the eawcy of carrent methods, . for children asid nagen." Very few indicated physioians must gain more confidence in their abil- : that .they: stopped to save money, for religious ity to achieve their goals in this kind of effort. DiS:.CHEST, VOL.- 54- NO. 3, SEPTEMBER 1968 ~" 1 . 13 Q0; 0; 74
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2eo uDtE].LLn _ , group of Lvslbac viGtirs and of co::trols wich resprct 11. . acmbcr of charactcr'stiu, among wcCcL wt, sttul:in~ (2). Tns that there wxu more lseacy c•iyrletts saukccs aatone ti:c.ru " among the trostbice cictias (tnb!c 1;. ~ ¢s,isi,tinterpretacio¢..t;,u~ buoci[itou~`~.`vioul'~-"b'o-"~t8e~56iicbc,,-amtte~ s::ola;rbld-;c ~ proecct:a- inQSetiib'.agnu`tlCffiostbtlA "Thr invrsti-tunc did cot iatrrprrt the de:e in such a msacr, but thoue!tc tant :r-n heacc smokir.g bcLit •x,. a+;rr_ Gna of. intrinsidemotioutl aad per<u:aity factors, ead thet tL•t--:,- factors were of etiological importnnca in frostbite. Thus, tho c e:dve statlst(eni ssaociatioa of frostbite aaS smolciny was considerrd to be a result of factoss that selccted indiyidnab for botlt etnokira• and fmsthlte; at least it was.so interpretal by thaw u•ho car•icd out this study. Ut:- viously, in an intarprctation uf stctisticai axtociationi determined by epidemiologicc1 etudies, it is importaut to er_luate the possible inAunucr " of this typo of selt-seleetien. . . . Oae app:uaeh to such on evaluation istlw comparson of smo4ets acd nonsn:o:•en with rtspect to varioua cnrsactcci3tics. Ii sntoL•en nnd nou- smoL•ars am sltl`cs in a ncltitr.do of other ebancteristies, it waui,d be difScult to secept a s.If.:_lection h_,totl:esis. IIow-ovar, it nlwuld be - empbcsised that if di[or,:aca aro fouad betweon smokots and con- , ffiokers, it doee not nece„ar.'ly meea that the'assniation bctasnn e ;• particular disoase and sn'w::ing is tha tssult of ;9lretito fectars. It u .' quite possible thatt the cliseWrstics in which unokets arul noasmosers ... differ may ba of no importu:ce ia termsof the mdociatiou of swa:i:•; to ~ the particular diseaseof ssttcrost. Ic would be aarissary to deterttine, by further .tudy, whether tbn cLenctcristie dseinbn:bbinc sanoksn from nonsatokets am indopendcatly roleted to the disease. If they are not so related, thou °'seU-saloction" ranttot be a reasoaablo o-cplanation for the - assoniation of smoking with disease. Ou tlu other hand, if t.fwy- rre . related, "aclfaclection" may be a reasanab:o esplenation. In line with . this reas7bnittg, inforotation on tbe rhur:utoristie of n-eampla of smo.l-ars . . wme of the issuea disaussed. - _ :. . . . . • ~ . . ~ . endd notwaokors in sa trban populac3on was collectcd during 195a. IMAis ia a report of samo af the resare of this stuscy that have a hearing an .T.aaE 1-CewPoMOn oJ aG! vieSVV ef Jrwl6fb an6 :j3 baek...r~n4 r~ruralo ~~.1 . . wswt ra doity onwet N•moki.q: Ge.o, rSS1-a:'t l8s E19a•"
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cxaaac-ca:ar,ca OT .t:,*:E-~~ A\L 275 Tw ~x i-Co+parucr. J`4ip.<:r. aa.,,4" n. r• .. ,.= . .''n..> r;cr,.±vd.o ' , c7...:•aw ..~. - : P - C.IU ; $S. V ID: wevl" !~l ~ i I Iri ~ j3, $ Aid d?y(ahrrp.nu, ' .7 Tete! . .,•. . InU.t• a>u: 1Jn.u '0 19SCO:Ywrr:u9:LU.ore..:.a.ac.:.:~:.« . . W 9autLL.on~nWL TA '_I: '!.-Corr,pnr.'aon eJ .p..r ' P:r!irf0:fi..o dwin.r!(i.::,:% . Alitelr......... .•.. :0.1 1 : A lat 2i . 1P(J<IpllaD 11 ' Gn+'~a.• ' \s:. ['CMqd 'lf :' .•..r r ~ .~''~ . . ... . . . ~_ . .. . . \otatail....... i 33.9 i ~a5.r. i A lltrY.,•.•....• 2i. 9 I:otstall...... 80•8 • A o[.•••..,.... . A G4ik.........1 ls A ~ 7[. (1 r Ti. S . !: 7 F :ba3 or noeeet: GI Cl ,.au: i I o i ii..,i ~r•J t <.Olll Agitlc,•_•„•, l2 Soia:all......, 8L0 11 :I : i 68 Al ketLell: - I ! Alittle..._...~.I KG ~ ?S:, 3S3 . IL2 i GOUI ilotauait....... 1 &J,:. 1 90. 4; A littlo.........~ S? C2. Nutaia:l.•,.•,• 7Si ~ SI•3 ft Y~,loi ( 2 2 I " , . ~ . A:a:lL.........; aL9 xC% ,t , 5„_U k i . ~ i . . ~ . . . . 61. :tilet.:.........I sn~r i 1 e. 5 .. 7~L C. .. .. c. 01 . Alot........... 9,5 i 1. rt 1 ~ , I .. I t V! m~ C7 ue. 1 Y o~r or barb atou: I I . . . ~..I . . .-1 . O So ............ .: ii8 i . . . i . :iotatall••.,_..f . 521 I s:,i 1 . . r4 ra, }.- s. /aL...n tVY+ r ()640602 TIFL 0305574
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tltS AND NONSAlOKL+Rti . i-. pneuttwqmpb reqNrat.wy mlu, 1Ithnu)Sis several wceks or months may have lah•ed between the two (r=0.69). Smeking during cnltcge comparctl with respirxtnry ntas shmws similnr trends to those givenin !he tahics for r"piratnry ntte Aurin,r tnedieal etantinatinn (P=0.0i). . Thtu thrre• is a tmttlcncy ftx nonsmnkcrs to be+lew bnathers and for hovier smokers to he rapid breathers. 'ISie habit of .mmk. ing is, of crNS.G partiatty a respirauxy functiort. - When one is a rapid breather, his tidal air is small and the dead spnns of the lunga are less apt to be filled. There even may be at times au uncomfoslahte ac- cumtJatkm of arbnn diuxicle in the blood. Smaidng perhaps gratifies these ..iullarer brmetftary by inveasng o:eygen intake attd bfowing off ctrbon dioxide at timeq ir- rMtective of other satisfaetiata. ff rapid breMhers (attd, therefore, shai- low breathen) tend to smoke more, we shxthf F.nd n rd:tinnship bettveat smoking and thfof air, the amtwnt of air inspirtd aidt eaait breatf, This is the etw whest tidal air is cnnrpared in the gtbups OS, MS, and HS, although P(0.t3) is not in the nnge of wn8dence. Ventilation per minute (the amount of air inhaled every otinute) does not show a ralationship (P=0.50). If msything the smokers have greater ventila- tims thu the nonsmokers. Xavier smekers also were fouud to xigh moro frequently duringg the pneumo- grapk rhan uon+mnkess or moderate aookers (Pa0-22)- t7u-square is not in tM esitga of eontidetue, but the finding is eensistent with the thesis thst smokers, as shallower breathers, ncsy neaf to 68 and enqdy their' lungs, at tinr:a, mnre fully. The henvier smokers swailow ntore fretpsently than do the nommokers or the moderate sntokers (P=0.04). Swallows aro recorded cn the pnamtagrsph as little notches wheeetesgyitation was suslicadet( while the subjeet swallaved. Presvmably such swailowing is due to excees sa6vation fevna the eQects nf the rubber nunathpieeq psychntv,ic.N or non The possibiGt-v of a T075906 3" MIN p000624 TIFL 0305530 TanalT.-ResPiratery Retr ~a Tiwr ~f Mrdis+i Bl+~xuxNbx Rsfofrd W Siixrlix0 7{ebJ. sm~r ~a xx Na Re gNS.0. a a~m a /a aa by the phyaidan, are two positivn which ruve important tturttitxc: nta and re8exes. inltOry RatG-flnt4tnlokei5 eCnd tn simwet respiratory rates than dn RespiTatory ratu were taken on aeosions: (1) during the nm6at ion, with the subjat in the sitting nfter the pndia was 4kea, and (2) time of the hasal memhol'nm, the hnving fasted nad being recumbenK tlng. 'i1he latter was recorded by ph. aliowing for the simukaneaus ng of other re+piratory fundiau: Gda[ air. varatiots of breathing, numher of sigh xnd svaflowa. Tnbkx 7 and 8 itive tlx rel nnships of rrspiraeory rate and the 05, MS, and HS chsaifreatloos. T ble 7 shtsws extases of OS tnasn with sto n.uf difh Asa for respiratory rates and excessas of HS with rapid respitaWry rates. (The entx between the respiratory means is thsn 3X P. L for 05, MS, attd 5, H5 di/Earences, but nnt (nr i{.4. H3 di8eratms)'. T bio 8 abavs ihe aarste «mds as Table shough P is nae zs low. Numerous Irvntlons bave ahown that penom hxve ieatory rates rmdar standard mtttlitions are cbaractelstiagy knr or high or ge. Thtp, for our subjects the tesptra- rata atthe time of the tnedital exatn• is rather dosely related tn the " Srelk RrkNd &.x~l 4 n eMwO feaM S tas~~,`1 :wiw ~y ~t Na [Ne: n~'.. u a m N.lol
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I i 510 lbSEPX D. bfATARAZZO AND GEORGE SASLOW when it a remembered that approxi- mately 0 million Americans over the ' age of 1 smoke. It is hard to believe that the would share in common one personal ty "type." This is not to imply, h wever, that the various psy- chologic dimensions along which smokers have been shown, as a group, to diffe from nonsmokers may not suggest n important single process, or proce ses, underlying these varid'Sts demons rated differences. Further research may indeed so systematize the disp rate findings. While the evidence for a smoker's persona,'ty is not strong, it is possible to think that there may be in certain individu Is a biological or genetic pre- dupositi n to a strong desire to smoke (as well s to lung cancer). To estab- lish that cigarette smoking is geneti- cally de ermined would require stud- ies yield ng more definitive data than are as et available.' Nevertheless, Fisher 1958) believes this genetic hypoth is has some merit on the basis of a reported German study of monozy otic and dizygotic twins-in which t e smoking behavior of 51 pairs o monozygotic twins is re- ported o be more nearly alike than that of 31 pairs of dizygotic twins. Fisher rites: The da so far assembled relate to 51 monozygo ic and 31 disygotic pairs, from Tubingen, Fnnkfurt and Berlin. Of the first, tbirty-thr pain are wholly alike qualita- tively, na ely, nine pairs both non-srooken, 4 After his review went to press, Eysenck, Tarrant, oolf, and England (1960), in a study of ,360 British male subjecta, reported finding t cigarette smokers are mare extro- verted t nonamokera Reasoning from Eysenck!a earlier work on a suggested genetic basis for his extraversion factor, they con- cluded, erefore, that'genocypic differences exist be «n smokers and nonsmokers, and bet een cigarette smokers and pipe smokers. They suggest a number of further studies to establish this hypothesis even more soundly. twenty-two pairs both cigarette smokers and two pairs both cigar smokers. Six pairs, though closely alike, show some differences in the record, as in a pair of whom one smokes cigars only, whereas the other smokes cigars and sometimes a pipe. Twelve paizs, less than onequarter of the whole, show distinct differences, such as a cigarette smoker and a non-smoker, or a cigar smoker and a cigarette smoker. By contrast, of the dizygotic pairs only eleven can be classed at wholly alike, while sixteen out of thirty-one are distinctly dif- fuent, this being 51 per cent against 24 per cent among the monozygotics. The data can be rearranged in several ways according to the extent to which attention is given to minor variations in the smoking habit. In all cases, however, the monozygotic twins show closer similarity and fewer diver- gencies than the dizygotic. There can therefore be little doubt that the genotype ezerdses a considerable influence on smoking, and on the particular habit of smoking adopted, and that a study of twins on a comparatively small scale is competent to demonstrate the rather considerable dif- ferencea which must exist between the dif- ferent groups who classify themselves as non-smokets, or the different classes of smokers (p. 108). Hammond (1958), on the other hand, believes this genetic hypothesis untenable: It hae been suggested that there may be some hereditary factor which results in both lung cancer and a strong desire to smoke cigarettes. This is an ingenious idea. However, if it is true, ene must asaume that (since cigarette smoking has increased so cansiderably in the past half century) a genetic factor of this sort appeared and berame widely spread throughout the populations of many coun- triea during the last fifty years. This seems a bit unlikely. Anyone with a good imagination can think of other such conceivable mutual causation hypotheses, but no one has yet pre- sented any evidence in support of them. ... Other evidence, such as the sex difference, the urban-rural difference, the time trends in lung cancer death rates and cigarette consump- tion is consistent with the causal hypoth- esis.... With so much evidence all point- ing in the same directon and no evidence pointing in any other direction, I can only arrive at one concluaion. In my opinion, tigarette smoking is s major factor in the causation of lung cancer (p. 350). It is Harr. denc posit is to tion Hc hypc that stan. tion ereae duri intei co¢1 and con ing, A side smc mui. sing type give havi minc cupz varit hav: mea perr van sinh sho smc a s cha: L it a stu! ans qut ps) smI the vie, mor ind: TIFL 0305554
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I3, 19)r f..raa I 19031 an in- -svcigltt aL snor- cretting Itts of rrinatat btf:mLa ,uud in as map e, it p, Cnr1h• tT pto- f non• ~ccight, olmulLl ' Low-hirln.waigln infcnls and malcrnol smo6in9 979 .nh.r 1 8kthweiqhl L 2500 0. % Mean 9estarion, days Anomaly rate, cor 1000 SAe,I 6,a,h.nL_~sne4~ny Tahan Telt welAer.~_ NsntmoU+q ma1A.., inl r ' ..- .-~Fl64 >.o I I 12 239.1_~- ' -_115]l 911J1 -__~1p1 955~ `~>l.> Ubt 119.1 iR9 Meonclnl morrelfly, per 1000 1uvn, . t17.3(1990 1.11 monlh. mcrtarly, aer 1000 211 ~-_ ]]e 1e.6~-------I --1:U Raproductice 7mrfnrmmrce ef norunwking and srmkinS Bravidas contnsted Milh thet of tall uul short 6ms'ides (Frcm Yenlsllalmy, J?). ) pcrinatal nlort:dity rate is nol highcr f r infants of sntoking rrutdters,'mtd (3) the crinntnl mortalitv attc of lotr.birth-tcnght i f.ints of sntakilg nmthers is subatarttially I uror than that of infants of nousmoking othert No rc:uonahlc ~phumtion for tiwse henomcnrt .tas found uilrn tlse data rtcrc lyrcd for a.arictr of factors." -A cemltari.wn of sntoken nnd Itensmokcn s m.cd tGt tbc two difl'cnd rnarlcallp along s r,ral cn9ironntrntnl, bchaoioral, and bio- ic a•ariabin. For example, sttttskrts are I ss likely to usu contncrpticc m9thods and t plan the pre~n:mr.•. '1-hc smoker is ntetc I kely Lo drink coffce, heer, and whisker; and tn nonsntok9q tea, n»lk, and wine. Tlla ker is ntorc likcly tluui thc ummno6rr to 'tdulgc in.Lhese h:kbits to tscras. In gcnrn4 t c ntsnsnu+kcre atv rerr-altYl to be nsore 4•ntc th:ut thc snrnkrLS tvlm are slwwn t be more c.trcmc atut carcfrce in their utde of life. &ynr hink~ia didoanres trvre Lro noted 15etumru thun. 'Ihus, stnuken I nee a higher la'innin6 ente (truu only fot hitc.), and Lhcir aqa at nsmuu<he ic lo.vcr t tan that of nrnlnnoken?a Thtse 6ndin.n saiau duaht tlun ri,mrctte snoking act, as nrl CSrPOCtIbW f:¢Wx tvhidt iutcrfern ttith tlte intrauterine dc.nlopmcnt of the fetus. 7ltc findings girc equal suppert to dte ht•pothesis dtat smoket: represcuc a group of lmoplc whox apwdt:ctssc ecpcri- ence uauld hate dnplicated tlte observed patterns adtctiur or not duy smokrd. :n other words, the obses.ed dilRTCUces iii inci- dumc of lotr-birth-tvci~ltt infanta mny be due to the mruksr, not tho nnuF.iug. :1ss indiscct svggestion tchkh snay jnvtitv the abovo spcculadms tru pru,'idcd by thc fact thnt ts'osnns ahu arc dilfercutiamd aloug a specifie biologic cbartrtcclctiq that of brigltt, duylie:ne similar <GIt<reness in rrproductiott as found fur stunkrrs aud non- snwkcre. Pig. 2 slroos tb>t thc pa«ents of ineidenee aud of dcaLlt of lmv-bitdt-tmi¢ht infants of Short and tall .vouun ~rcte ucarly identinr1 lo Lhat of .u,nkev and nonslnol:cls. 'f'ho lfiflvrrncc in incidcnre nf Iott'-bitnl• 1cciGht ildauu hcluct•u sluokiug nnd non- stuaking ..nnlrn wat idrnticai to that 6c-hrpcu sinxt aud idl vmurv. Yllc s:ultc tra.1 truc fa• Immy of tltc dmmcLCristiu fnwtd for (nte-hitth-a'right inf:utts: inran Imt,tlt of.gcxtntion, uronatal dcath, rntc of sct'cre rnngenit:ti aMntmliea, and Iwstncoualal dezth. TIMN 25462d TIFL 0305518
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'-»o~i; 1 s=a (3i: Selcctmd CZ::=- acicriaiicg of Ci~aratic Szzio':ers ¢s•.ti 3 \o.-ismo?ta:'s as Rc?aicd 20 Epid:-nioioo- ical Studies of Lura Ceztcc: ;.z;d Other Diseases , ' daaass. NL -r ra.- p:LD. .•.LP!1» D:pan. ment o(~adti.yia -crsd -£,idcn<i'wpiad P,c'y+vat. Xusscll P;uk ]Iwear~l lns:itsut• Y.ufjuc. \rew y'an': ! • Sssmsaary - - Ir. 1936 o pro'aabiliH~em,,le cF tSe c.'ult :opulerions eF 3cEala, IQzw Yor., wes int¢nri¢we2 to dalarmin: wh¢lhcr cigerana smaklea difF¢red 'c= nonsmokea with respect :a amo;ioncl aat'u and e:hcr s¢lectad chenacisEe. From this samp(t, greups o: cigerene smokars end non- r..-rokan wsre matched 6y eg¢, s¢x, --ce, ar.o secial cless. Tl:is com• parisan inaJCarcd tf.at tmpkeR al.{af f:am nJns.:AkCR in their regles_to ° ° " ° Cuestions concerninq emotional sA:cus. E~cTetii?imafiie r r- m rnare ou.a•'~a"' m1P ~tt7 zxt~htsmciaaaFtar,ipnoiw:7i:erf natt ar• - .c~+n,r~,o~ r.,-, _t a~onsmo.een. Abo, theat pai~ " oeaoeasaisfi. •! .`bnnethen~"irFae`ors~ufc,erx No di6aences werenoteda in bir>haioee, religian, advxtion, pr¢sent masitel do/es, and proportfon of iiietin¢ spent ln larg¢ dties. Peuiblz inte~rssetsom of tSae results ar¢ discussed, emphasi:inq their bearing arl the statistieel eaociafian of cis=rsr.a smek:ng with hm•g cancer end o:•.n disecsa. .iarimseodi.drsheoegeaecoi.,difEer¢nce,,. boiw¢.wsmeliee:m oswnokec,s'ias..Ea~~tG;Se~~,rro~ai:cocnrfct:the:;• kiq~deget:o(r~..e ~:ee~b6awacn:d;ei•.te:',anokinq.ond.;luag eancr^ and,dsavos~'ocoisb3orinffaeua..~ia ceusai_~r.f¢t¢9ea: desfeed.lromthia _aaopch~lheu9~Yii~au3~~CSn~flT3en~Stas¢xPFeimthe~associctlon• a6•~ . uSa' ei6- elu'isgirftlepe(f- .'tCU CGafOnesy~asfardis¢qy _F-unker sludics are needad to tasf : esz Pcssibihl ~es.-J. \ai. Csncr S.mt. Z": SA-°31,1959. . . . 0 af tba oLjections~ to iaturgrec:ng tlie atatistiral essocin:ien ot tto aaokir.g with lung cancer ~r'_ oWCr .li:aucs ut indicatine . ' reL+[iondlip is that the essecic:ion n:a; iw: a result of "aelf- . sdc iuP" (1). ~ VcL3DV ~a : u~ t on_sn. ~ureto.~iacD . 7ee[m 'i;4lldttEMwc~',MfWe tvpe uf :¢Y.suniag is ilivstrsLA in an epi- - . 's~sra~~d_t~ei,e~id6'iet~r.cziarL'oss•w~m8tioree:; ~qCpsRr~tta~Ween3ME.YSfm•cotiiass~mr.oEmg! . •Tneawn~in.a.w.eietwaM..•Was:GVmtxsrs:~.:'r=leaaa.rra>y,u..~.~a . j . +.+.a .tIWL•.!.lsd"aYu'v•S.e.In. . . . . I tintnv-Dw`JSea(ClwabCaa.x:'S.4'.-:•~.;.i'mt'.! Ytae!de:l:n.w.e3T:aJe- . :..~.. :.. w.:.e~ DwCUVn<.uu. ?59 T o0z0see I PA -000497 TIFL 0305558
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SNOKGAS AND NONSMOdSRS scieqStifie eimrs;the smokers, areers in relmiont, edumtlon, andL tvritin& Modermc smokers woe repxsrnted pre- {nnndy in business and medieine. The mokers e<pressed preferenee for the mr of scientific resrasch worker but da- likc for asscrs such as sates snosusger, tor, mrpnrsiton lawyer. The heavier rs wrcased few prefertnccs but did the earter of judge, disrkiag that of sct ure rexrrAs worter In Wodd I-Par II msamokets wera listed segnlQenatly in b cha of the Navy, hesvia setokas, in efx Army. Betttr adjaument to the armed was shown by nonsmokcrs and e smokers. Heavier smohars were among the mea who bad combat du. There is slight evidmce-not eaw el .e-fram a study of psydsotype that a okess tend toward cerebrotonis, m tate smoken taarard stmatvtoois, aad ssnokers teurud vis•-n+ s Nen- sm~hers answered a questionnaire mcre ly than did the otloss. compaiisoa of smoldng habits with a wibe nriety of physioforie snd medfol da* such as physical fitnesa, heigh4 wNgh4 ber of colds, pulse, blaod prqsnre; and tan xcmnpasying srressfnl eF , gsve larselr aegativt results 6 fmdiogs. Lowe.er, are aateworrtyy is a strwsg tendenr.y for nonsmokers be sfmr btrafhas aod for ba.ier te bs rapf8 btnthers. TW& was by puemnogrsp6. tahen at tbo tsme the basa[ ntelabolirm- Rapsd bresl6ing isI rdated to, am¢ ndat air andd suggests - nred: fbratasioaat dap brerths (as ic- efglrettn). gtiYfrl stnohers Sigh freqaetlfy- 3nd swallow more fre- y- when thve is a rubber tewthpseta R}htionships of tfwse' cespiratory phe- with pas®lity traits saggest eon- csn of traits assd physiologic facrors tb smoking habits. 1Cnte, snkle, bsceps and abdominal re- ft~os show treods which suggest that they m differectiate smokers as a cl.vs from n tumokess. The sefteces of smokers tend to be scdviced. Such rerex,s also hive sug- ge.live relatious with tr.uts and respiratory rates, thtrs asfding to the aborcmentirned tonstelhticas. . Other find"issis are that the heavier ' makcrs i,du[ge more in llcohni lnd ia coHa than do thenonsnwhcrs; the modente smokcrs tend to gain more weight during the years, the heavier stndcers to tose wcigbt; the no.smofxcs have (ew body nsales, nlthough this moy havc beea due to chance distribution, despite a value of P- ODI. In thfs study the attempt was made to cross cbcdc whenaver possible with similar dats (foe etcunpk, respiratory rate at the tirm: of the medial etamination and st the time of basal wetabolism, respiratory ntes with tidal alr, and different Wnds of re- rc:ces)i This was not passih[e with skin, atoles. The charuteristia whieh seem to differessti.te smokers frons ncnxaoktrs (fcr simplicty on9Cing the MS categery) may be .utntntsrsed as in Tabk.11. 'l7see semss to be Gate doubt that this group of inen eus be differmtiated as to smoking habits by certain pessonality traits and physiotogio aiteria. Although the +ob/em show a wide geographic and toeie- emnomitr distribution and in many ways luce di.rrgeot personalities and physiques- they are navctfteless restricted to a seg- utent of mregtmea of a certain age and in s:mse respects to an intelkcttnl chta, For 'GS~areewApa °~.1~sF(esofn S°Itkaks .°4rr °/ 94010"U" i.:'~~m1~~~N!rt,~.p •_ M plvN mti~•L Ca nea~°iWYti.Wnt. aaxmeti.ns.wtr nwsn: aM una.r rr'IFr1p:~ rrnW Amn•werWYN A~WW° i~WfJ~4 R,r~ua~YrrrM°:nor rs.Yla s..wrewwmft T0'75910 a«..rt.w. 1h IvNb1lYtYt c~uri.n: r Wii•MnY/Y~i Ar am aw.Ya smarc .rrae u4•ym NTFWYOr.YVnYW W~Y7 Yrwerc °umr> AmM l.nN: Amm Mt 7~w~IyW~rIpr~.~M, maMt M eltNw°. w.rs~rea° R.e.r« de.R.ma sunNtalmuurar 397 TIMN 0000628 TTFL 0305534 ' 7
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t 512 JOSEPH D. MATARAZZO AND GEORGE SASIAW marize in Table 6 make clear that smok s and nonsmokers do, in fact; differ n a number of psychological, person 1, social, and behavioral char- acteris ics, it is equally clear that re- search in this area (including appro- priate election and sizes of samples, contro , etc.) has just begun. The number of recent psychological stud- ies of smokers and nonsmokers sug- gests that publications in the next few years may reflect an even greater interest among behavioral scientists in this very common form of human behavior. REFERENCES Au.aN, saNADENE V. An investigation of the te ationship between smoking and per- sonali y. Unpublished MA thesis, Univer. Portia d, 1958. BAC , E. M. Advances in preventive medi ne. Prarlitioner, 1958, 181, 494-502. BEEGLE , E. Psychopathology of compulsive smolu g. Psychiaf. Quar1., 1946, 20, 297- 321. BExGLE , E. Smoking and its infantile pre- curso . Int. J. Sexol., 1953, 6, 2t4-230, BaonuA , K., EsDluxtr, A. J., & WoLaF, H. G. Tha Cornrlf Mcd(ccal Indez manuai. New ork: Cornell Univer. Medical Coli.,1949. Baozes, J., & KEn, A. Changes of body weigh in normal men who stop smoking cigare es. Science, 1957, 125, 1203. EAar, J R Cited by A. G. Ingalls in If you s oke. Scient. Amer., 1936, 154, 310- 313. Evssx , H. d•, TAaaAerr, Mou.cs, WooLr, Mvla & ENOLAtm, L. Smoking and per- sonati . Brie. med. J., 1960, 1,1456-1460. FtsasE, R A. Lung cancer and cigarettes. Natar , 1958, 182, 1o8. GLESE$ GOLDINB, & ULETT, G. A. The Saslo Screening Test as a measure of anxie -proneaesa J. din. Psychol., 1952, 8,279 283. HAetr W., Sanattr, M. B., & Mn.uan, H. P. Tabacco smoking patterns in the Unit Statee. Pub. bkb. .Nonogr., 1956, Np. 4. (Public Health Service Publim- don, 956, No. 463) HAltuo , E. C. Smoking and death ntes: A ri e in cauae and effect. Amcr. Scien- /ut, V 58, 46, 331-354.H.tttseo , E. C., & Hoax, D. The relation- ship tween human smoking habite and death rates: A follow-up study of 187,766 men. . Amer. Med. Ass., 1954,155, 1316- 1328. HAxaao o, E. C., & Hoats, D. Smoking and death rates: Report on 44 months of fol- low-u of E87,783 men. .7. Amer. Med. Ass., 1958, 66,1159-1172,1294-I308. HAIeMOND, E. C., & PERCY, CONSTANCE. Ea- smoken. NY S1ate J. Med., 1958, Sept.. 2956-2959. HEATe, C. W. Differences between smokers and non-emokera. AMA Arch. intern. Med., 1958, 1D1, 377-388. HINELE, L. E., & Wot.re, H. G. Health and the social environment: Experimental in- vestigations. In A. H. Leighton, J. A. Clausen, & R N. Wilson (Eds.), Expfara- tions in accial psychiatry. New York: Basic Books, 1957. Pp. 105-137. HoumosasAD, A., & l2EDUCa. F. Social dass and tnenfal illness. New York: Wiley, 1958. HosN, D., Cotrnrs, F. A., TAn.oc, R M., & SoLOBoN, E. S. Cigarette smoking among high school students. Amer. !, paM. Nkh., 1959, 49,1497-1511. Httu, C. L. The effects of tobacco smoking on mental and motor efficiency. PsycAot. Mencgr., 1924, 33(3, Whole No. IS0). KALLNBa, GEaTetmE. Smoking habits of the population. Stafist. Bull. Israd, in press. (English translation of a mimeographed re- port, Central Bureau of Statistics, State of Israel, November 1958.) K[BcaOFF, HELEN, & RIODON, R. H. Snlok- ing habits of college students in Texas. lez. Rep. Biaf. Mrd., 1954, 12, 292-299. LAaaoN, M. P., & GoaalreN, AE. Cigarette smoking and attitude toward the etiology of lung rancer. Amcr. Psyckologisc, 1958, 13, 342. (Abstract) LAwton, M. P., & Psn.ues, R. W. The rcla- tionship between eccesaive cigarette smok- ing and psychological tension. Amn. J. med. Sci., 1956, 232, 397-402. Ln.tsahELD, A. M. Emotional and other selected characteristics of cigarette smokers and nonsmokers as related to epidemio- logic.al studies of lung cancer and other disexses. J. Nat. Cancer Inst., 1959, 22, 259-282. L1TrLS, C. C. The public and smoking: Fear or ralm deliberation. Atlantic, 1957, 200, I i .74 P LxN sr vz R. (C Mr' so aE MA' A' th ar P Mn cl n. PE. E RA~ L. Rus ,i RUT C'. 41 re: TIFL 0305556
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t ~a:z... >._. . -- A. df. A. ARCffIVG4 OF INTF.RNAI• AffiDFCENf TnNS L-4vr.nwry of Dete ue S+unkwg ffnGifi Clv.na onh' Yte Caft11M~1n, I+w tlw. 1-1 1 rsbri .IM W f' M Drl1y' at Mw. I<~~ UJI /el Tl el IAa Iwi f0/ K as u u lu ua vs ma sr Iat pn ua • L 01 la, us y 1 M ~ l y Iw. u L y ~ IY Ia.i ; IaA an .u N; ii A Ioa xus vs TJ i.i U IY >~ ~ 31.4 ro~ ~ ii nt• y or intermittently. Only 51 man have and 51.491, Iha largest nambers fallbsg dur- ing college and in recent years. N+hen oue con 'ders the history of nnokink over the wh le period of some 15 yi.nre, the numbvs of smokers are eonsiderably reduced be• ca a of thase who took up smoking tend- a nonsmokers vaded between 4429'o smoked (20%). The table shows an e o£ hesvia smokers (one packnQe or pe or cigar smuldng was Im frequent eiganute amdting. Cfgar and pipe packages a day in 195t, r to 195Q F•leven maT smekad two or at u timet should be dixouoted Relatively f nxrt nrwked hvo or more padmgea of ei ettcs a day, not mosc tiran four nsen ntemrittent espcrimont, and the figures daify) tu a peak of 35e/v in 1943 and a diminulion of atnstbera to 29% in t yws. Smoking dtrring college in to 1942 xas, for nwly men, ntercly g will be essentiatty disregarded In d one or more padr.iges of cigarettes du all of those smoking up to 19 ciguet- tea kaity nnd also 30 men who were chiefly ci , or pipe smakess. The remainlcr; talicd hea icr smakers, tomlling 96 mm, or 35195, etvtte sntoken, 95 mclp or 37.7%, in• se tlen of each subject. The mcn who eev smoked aya grnupcd with 10 man wln am rarcfy and intennittently only before 194 , and they ;ve considered nonsmokcrs• Th totaf 61 rYtly or 24.2%. A group of threefold dassiftauioll of smoking has ooestrtsemd, based tlpnn Inng•tenn ob- the present study. dnily, cither nlntinmwsly nr fur a nrajnrity of the years during which they were fol- kswetf. .. IT• Personality Aif£erattees , . Caaa Daecltptiana The records of the Study uf Adult De- aeiopment are a rieh source for cve descrip- tien. Verbal descriptions of peraons an suppfy ample evidence of persooality dif- fenytces without lerAing then:selres to any easy statistiell hand&ng or proof. A tead- ing of records showed marketl differences between some of the smokers and the non- smokcrr. The fdlowing brief ase deeerip- tions, solnewhat disguised, illustrate this. The 8rat Sve etses are the man who smohed moaa he,tvily (two or more packagee of cigerettes a day for a prolonged period of time). Furc Hraoiat Smokera Gsc 1. A p,edlet of a ruor fandty, sith doeiwlfas ankd Nreels, he hal to wo,k h•s way thruuaL mtkg. He du.e s.Wlpwm braneb of the almed servke dluiaq dle wnr, olm fer whieh he bnd ukaitud w.w fear, vld ful6llad his dmla watL Acdve T*7strN wer£: far 2 large fimt whkk un salndmdi for emOkryees but pro- vides hauiuq; panlon and insaranm plaa Sane msriod dilfavulss: Samewhu swVlcous at otAen, Cwsa 2-Ilarddriving and urivtng worker. Remarkable randnt rrcord during the war, indud- ulg lon tlerials of denaeraus Rehling mul sewat wauuLL Psyehosolawle syaptems on relarning to avilfan fife. A atanly <ouruhiq but evtntualty a auemafld nnrringe and sutuafot caeeer. Aa- aresiive worker in a highly m,nPetitive busincis Rdd C.Ve 3tTlds Ir.u was rmt off by n braken fimily at aut nrly age to ,nnke his own way t'n4 1o1, FeA., ]9Jd T075901 TIIyIN 0000619 .......---- ........,--..._.-,___ ~..._.. TIFL 0305525
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TuwulBroup , . aJY1.A 4rlly' _-__- 1`ereanl ufl ra lwnu• in xlJclr eiKerellu pnoken •U'1 I (+UI p/nnre (1 Aryrr dn.~~ 1'orr.rol of rvaurnl••y In aidrh cil:.a•11. elrWla'!.V nn. 1 <'IJ .ul.wrv f rlr~n .f frrr-' ' , wnnnoCrnl nerteJ I uurnrnVl:erY' '1 u1 , St4 I L. :IG .0.1~.• r~•. 0'd /1:. 4 0.:11 ;l'>.r. 111 9 -' 590 ,. 2s OU. 2 1.27 59, 11 dLL 0 - 4. U7 LO •1 8. aS <.01 47. 1 43.5 3.26 . S0> /'>, 05 40.0 1. SJ .20 III. B lIK I 2.02 .2U>1'>.10 83.0 0• 0P1 185 TL 5 1.62 .20 . 7LL 8 0.07 .80 23.2 52. 0 I.L8 ! .80>I'>.20 Ba. 0 0.20 ,7>J'>;L 0•!. I 17:'( I.01 ! >•]0 c0.a o. ;Is ,7>r;,s n, 0 q 8. p v ~ _f Q 91. 11w* yon a•er LnJ any , ~ . ~ . InLN!u8 qNa!aT , I Un l~wl Ullu J'uur Onger• C ' tC Nall. nnrl ;. tb .~ 23. lln.'. you cvrr baen ~~ UolLera~Uy rcunnesur 1 _ - palur /n iho Yca41 ~ - f'24, Aro')vd ctr! IrouLled' • -u'/lq Nek Or.JncLnr7 f ; rU710nIrJ /11'utrllONntllrr o11 rrnFrrYNV1.MOIYr I1( JyrY1 r/n1lrfY/f p0 VP .1 r1pCrr/If, rM9IY rr 4Yr/ nDVIYM!!'/IM~ f,n mak pv..xr w onl9, anJ/or arorY rnoGrM ady---Qqninu.J . 10 17. Io eonend, hnu- .vonld I pou ay 7cur lenl arusL ul U/O /inw, In Ouod cplriln ' or In luw aldrllu} 18,'Are )•.w evcr Lulhcrcd !.r Ir.vInB niFU/marM7 19. llu )'uu ollar hNVU lryu- IBU {n gtlliu8 lu ulrwp or : .I.yliyl lwIcy.T 4E 20. lluq•" oflrw rlu people >Y ~8r Lurl our j Ilr.'.vv suudnrn I 1 9 7.t 1 .10 0. 12 1, le1 2,58 .2>/'>, I 1
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/ , T~e4r: I I--Cnln)uriun u! a~:prllr .Ywt:'rn on./ uunurx4'. n¢i/h nyud lo at:rird lhYr.l.i. riNin 'TY1nl tt.Ylp ' . I CIwrYGlrflaic 1. ..... ..q. !. 1.un.l. r:.1 I l:lw a uuvrlyd. .., ~.NYYd.~r IJ lo.q:hnli:~xl4.ne...... •1. NNelrr Yf dllirrvua naLlr•YCrL .. 4 Kur:16:•r n/ S-ny ur Omwnweple eswnq:ntlmas.iWiae 17 umntd! pnroYAlnµ Io1rP9eY .: ........:.. B. Kwm1Y•r ld X•rwr nr redluu: IlreUn:•INe durlul{ lif.ihwe... , .. l. \umbr•rYflqnlrls...••,,•.... . FIIM:1,•'rT I I ulLulr 11.-YCC emr.krre nYIA' .YYr4~r) ! /IliYll• J....a ; S: 1' \I:d~..:nlc .Yxdrn I la.n- .I'.11 u-nYl •15 I i-. 10 I 1. I:1: , 10jP;,.OS I -.01 I 0.12 I . JV
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75. lluw woulA )nn, sy Iwo01s yW twlw 1r.1 µ• nm<h :Lwt lhium 11m1 I ndgbt lmlqmn to yuu4 27, LL'lu•n yun xerc µn.w'luµ up, did you Lnrc my uuuhlr wllh aulleriuµ In lnur apwrt.Y 2B, Iluw IJbv. oru •p.w Ix'11r• er.+l bq Incluµ nn u1M.•t N•nnRdit 20, 11. y.,u Lnr" wn_c p=w- IIrnL.r ply'drid w M011. IK.I1.11'nlt :111. A. /ur w. /.,'. l..o. ....r.. Ixrlrr...Ll/ wr• 31. IM r... u.uxlly IiL•: 1n Ix. bI ronrall ur to 1.• aflLolLri /+.•/•4.• 41.1 1111.11 49.1 III.:1 0.0 Q1 n A. f dt b B_00 ao2 0s. A8y I IL1B1 jk~l' •11µ 0. 3 111.9 i 1415 ' .TO I 1• , 11. 3 fi0 ,10>r>. 05 0.43 a. 0.93 . Bu . 41/"?. 6 :dA 1 ~ /L 'lt. I . fAl I„'ll'•/••,1111 1,41.7 I IN I I`, u :-a
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67% wE ACCURA THAT E 3ELOW DOUBTS WEIGH E oRE,-WTURE, "ALTrfOUGH GESTATIONAL AGE CANNOT SE DETERMINED AS ELY AS BtRTH WEIGHT. RESEARCH WORKERS IN THIS FIELD TODAY AGREE EN A CHILD BORN AT TERM MAY HAVE A BIRTH WEIGHT CONSIDERABLY 500 G. ON THE OTHER HAND, SOME RESEARCH WORKERS EXPRESS THEIR AS Ttl NNETHER THE RELATIVELY WIDEST RANGE OF VARIATION IN BIRTH IN THE EARLY WEEKS OF GESTATION IS REAL.° THE RISK OF PERI- D YATAL GRTAL[TY WAS~HiGH£ST FOR PR[MIPARAS AND 1NCREASED AGAIN FhOM. t 9ARITY 4UPSVAftAS;. PARITY WASALSO PtlSITIVELY CORRELATED WITH BIRTH - xEIG HITH HkJ HATER ' WAS •A ~ ;~1 , ~T~A a T :THE qpRTAtll'f 3YA°CES` (lK J*'$o~,t THAH 7ne R~Te~"~a ~ .. , ~QRH,.::a6 • ~~4`~'f' AEF~RE~LCE .FS MADE T~G`lHt;'h S1'IflttE@ .N`Ef~',:w . NAyE... T' T DIt-'~E`klaAL`'~'~ REGARDING 'IHE"EFF`E0OF MA1ENTi~.`~SI~OKI. 9N`~I~R n 6E4TATZTSINAI: LEN&TkI. 14 A910UNT OF kOR1C,: ` P~R/ } NC~'~A,SE_T{~E RIS.K~ R:F,~i0N aTI~TH Nt~~ 4` V 4lORk`1RCREASEu TaE R[§K 0 ~F P~9 apR~i~o~E. T~ M(lTli~ ~ S~ SA~JtYA~CE~ Pt(``~ PEihdATALt DLBWT. Loyk`8t ~~,AN~f it MA~$E`'FHA4~TlfES"SITE t5.AS3"~GI+[[EU~ ~ HOttK. THE':i.EdEL.o~ tTitltlSTg 1AtJZAT79µ OF Tj{ K ~ GREATEST JtAPORYANCE BNLY FOtt PERJNATAL . DEATFI, R7 AL:N'6 CHANflE OF RE~JtiEN£E~ INS 0fiOCJATER" ~ WlTifr GR'i RATE YtAS-:I4ENTiCACV`. L~t A~'•~[~J6 INCR~SE~`~}li§ ~ItS~T~JI'Y:I"'ik;EfTFANTS flF~7~l ~`~~OR MOR~.. SMO~(It~(r~J5Ckf611lIA'fE15~RAjFiER TOYGIR~`IQs 'f 'wM L[~i~ FK THE ANASErC*NCE*ED` w[T!{ 1APJ$IRTH ;- jHE_.R;SK OF.PERINATAL MORTALITY ANO LOW BIRTN WEIGHT INCREASED -~ XAt~~_s"ANA-L AGE ANI7 SHQIIT hIATERNAL 9TATURE. LOW JAATERNAL J~ ~tiC~r A~6`~I~THE t~ISlE pF COV7 $[RTf{ NtaGHT. BUI 1$E CORRlLATION CF ~ , WEJ2~"i!Y ~!Y ~Jf~ATALa~b~ITY :V7AS Lt:'sS 09YIOUS'. ' E!•LESITtnaCY : E~$f'~ P~~C_ r<L~ ANALYS&EAEPT~fOR P$B'JRATAL 1*~THS OF;.2SOQ 6_-- R GARbtES56'H~4 THE .SfSC .YCE,GONdMt~ YEVEL GMA$:McASIiRED, t~ ~~ ~~~1~REX~~ T~ ~af~`O~~IITGi V$TR7H' W~tUHY AN~ s: ~ 'ft'C TlMN 254182 TIFL 0305505
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cttwntCrS::aT:cS qi .tsD SoS53:os_.^_ _°77 a.:.= 10.--Cmwycriran ur a;:^.'cc r:i::-: :r« .ocrr.a':.r: lr..^'. rrnr:~ :a rr::_er: Che:.criritit ~. C'aet! . . e_.o.c.s ........:•r. . s:.-. IlKina: CaGOlie..........i Jew~i L.. .........: :• i Oll:c :... . . . . . . .. .' U. !r So~~....... . ...~ 0.6 ~ Y:n:yn; \Larr.rd........... i1._ l': id:.rruA......... K nWOrcut ...... ~ ~r.r.ud...:::,' ~ 't' 1 X-a•ornwrrimt.... ' !•Co Aamal.a.........' iL.^. E ucat!oa (atnal• . n~enn 1~1•cli: \onc... o:,-m~te:rho_ kml tL.:t Cn.de •chnut 1 cnr,ypl..rpl . 1 i. S ll : W. /t SCn.b l:ICl..c'uyd~ LFgh .elm..l rr:na• : pktN........ : :L . Atrtnded vtt.in,.: li.l Yvttcu.. ..... ;at n ~ p . l'nit<rt stxtoe,. . I',. 4 . t 1. L 1. 15 I G• tW 1 fioth hurn •xlt„idr ' ` - IInirrd ir~c. :CC 3 ;1 . ' P ta' b¢thpt:ue: Both born iu I:nItRL 1Ltlc... .! Oee 1r.en it One ur0'e:h un- -• . I knoan... ...... ll G. 0.!. . ttl~er: ' . BuRwG.......... ~ S2'J j Ita r n( L'nitnl 1 i S[nv~----- . / Y1:. ~ Pn'snd... .. .. I. : _ L'aly .............: 3. L • Othar onr~u:e ~ United l4uh+....j ' 1R 1 loL•iR;, in ct•nlant9ng :kaie :•nr _a•' tactor. _Ltcr stirEt ndjlWtotrRL, 1>,~rn t o'4!rlmn" faetar is stFrl p:mcca (7k. Tht+w• rtrijuatmrnts have 1ICd to [tlaCC Of rC3trICRh' tlL c 4pp•ICL• ti11tC lL'37:nilf Yt thC time of u lun„ cr.ntrr (6). Hua.re-, oi....., c:,;.!tru.• smokipe 4 mur.+lrcr•tv.•Rt it u:`r-•n thec in rural srpas, it 4or-'lw.•n Rocc+>urn to hlijum forr,igar<ttc . v+L OL Y.- a r.Y...r rWe ./ WVMLOt1~ - TIFL 0305576
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?n° uLtS]rS:.D . Stouff.r enIf eeicr,r`:urs ite:ns in the adju:xt by qccs:iar.ic;; a g=np of •.r.urT!1,•" nn,? ..... .arr,ibs"; t9,: nospo^sa for each iieat repurtad. Tce :il qucstl.-r- ir. :i:c pr.•S<nt studl• w•ecc ai:o.r in wl:irh thcrc l:'cru di: eroic :ryw;so betwcen th.so •'no;n:al" ..:.•f °nourotie" ;,Tml"a. To compare ci,e,arcttr, atr.~~ac': .:A e:ourrno~:C3, tt P'1L rn,y;Ld.:,.i ncca.aarc :hun the 2 gruup. Lc xith :0 agr, soc, raca, r.nd snci:d sultur, sinro tl:ose h, i::dep,:u:an:hrrburvi tu tbe ehkractcr'utirs of intvreer. Oci or tiir total en:nplr. . of 1A'13 prrxa•st cignr~ttc tmokrr3 n'>= m: Ichnt witS u gruup o: :ruc; With raapoet lo thu fue:r e}c, s.•s, ra'a, cibt vorGil stuua \an- smol:nx an: deL•neda:< thu>e tr.,,. i:nd <rnnlknl te:i thcr. 5 t.. 10 parars of GI,C,ar::ttr5, lc.i Illatt :iU40 i i rl•,'.npa, !,y6 ttnm $ tn 5 pal'i:aoU5 or pipe tobneco, unJ 1:arl ebeln.l t~r. 3 to ~ p;ue of cSewiag tobacro duTtcg their lif.titne. For m.trbiny `.,y sgu, Sy ~+ar a.c a-meps were :u.~! re'.her than thc evtr.t age; for e.ram f:.-. q sninker R:, yrars of age n•c. rnetched with a nnrsmoker t!f br,•tt.•.•c n al .mii 7fl.6 Y:•xn ni ugc. For aocial status, the matching a•ai_et•wmpluh.•:i i:y m.i:.;; the aoricl quarculo of r.~idcucu. Tluqc were deternuitrd rs int!ou3: T!n• 'rrnsus traeta ie BuiFato weri nnked aeeordinst+ nl«dtaa au.:'::iJr ::~aal es rletcrmi,ed by tha 1950 census, and thca asarn:i.!a! i::lo quurtil:-: so that uppmsiamtrl. :S percent of the city's populsli:in iell into cne!• qunrtile. T'•onntore, a Dcilfalo surbttrh, waa consiJi:-crl nr n st•pnrate naft fur tnatrawty, puraoses. Tba mnlien tmmlLJy n•ctal w::s eousidered: a eaiid indrs nf rnlxtirc sooincconnmic ctat:tt heeaycn uf ia hf"!i cnrrrlatiorn u•itb other•im4•n~, sueh as fnnti?p iacotoe, ycers of ;4•Ixioliag t+implcttKl, uui o¢eupetion. ddmittedif, thia ir not :h:, rmnl reAncd ir,•lcx of norial staeuu, but it wss . tha raost practi._ll and eppcaen atlvtunte fur the prosent purposes. Tho distribution of tbis lnatci:cd gnu:p hc ago, scr, mrr, aad socia[ o,uar,ila is prt•scottd in tal>hv S,md .'.. t•b-m t4•x tablea we note that a rest T.aai °-Aianhulie. •j wntrn,.t gro., y end .eamukrrr, Ay ..". 40-44............ 10 60 TD 1 I. 6 I.: ' / a0 . I Y 5 7 ta-LO_......:....~ 40 7•_ 4i ( ~ 77 '! Ot1 a0-St .............. L.S : SN ii ' 2 fn 6a 4 17 60' 7T .......... 18 I1 SS 2 +. 2 1.t 20 42 92 ' 60-rA............ I'o :S "1 il 2 0 R is ?S 43 - a5-an..........., 14 13 ta ..1 :.•0 1~L 1323 2: . 70.ad orer.......i 1S 14 f ./ 0 • 0 0• ~ Is 14 -' ' 29 . .iY aEp..-........f. Y70 _I GOI ba l9 i 63 E3 S39 i tbi 00.." .~~ . ]S-W.....-...:..f- Ii L8 i 3" r` / 5 3 ~. 14 ~ RS ^_11-.•......_._. St a9 I ln 1 r. 1 f 7 .^3 1 4 24 ~~...._.......~ 70 i 9' 3 t 14 ~ ( .3T ' l5 0 30 30-3i....._......I L7 Ti ' 1 3 f 12 JS-78...... ....... 13 ~ ~ 1nS , It 13 l'r 101 S~3itr Ago Cnanl.itv SWthneo ~ . . t}Tya Fa. U',tS 1 1.Gt„ ~ F.. I 1'.n41 \INa I Fa lb:h . ~ meta I. new t : mal. I w•vw 7 I tnale ~_ es,~ wwJ .r .M 4a..J Gr. Lw.w. :
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r l The I-fealth Consequences of Smoking A Report of the Surgeon Generel: 1971 II.S. DEPAET37E`IT OF HEALTH, EDUCATION, AND WELFAflE ' Public HeeltL Ses.iee 7 0o:!oszs TIFL 0305599
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CHARACTERISTICS OF StfOKERS AND NONSMOKERS 507 studied, st (1951, to take to re different br its con- iilities, es- j expect reports ;h school yield re- it similar to others .iodology of fact, e longer of 226 s college 2 reasons )eginning Ike those Schubert both his ree scales and Pd) ionsmok- :ve smok- n, Berg- is of five who un- -gests ibstructure ited a spe- comscfously 'o counter- from their =o the wish that they ue outward oral "paci- of his first HE Tp,1t- ~ smoking ll-known. al., 1956, 1958, p, 26) place the number at under 2%. One of the best studies is the r ent one by Hammond and Percy (1958). Hammond and Fercy study. Their pulation and results were as fo1- lows: f 3,560 out of 5,992 men (selected from ephnne directories all over the country) wlko filled out a questionnaire an smoking its, 2,498 (70.2 per cent) stated that they oked cigarettes regularly or had done so in past. Of these 2,498 men. 472 (18.9 per t) stated that they no longer smoked ttes or tobacco in any form. A question- e asking why they bad stopped smoking w s sent to the 472 ex-smokers, and 333 (7).6 per cent) replied. Only 6.3 per cent of the 333 ex-smokers d that they gave up the habit benuse of reborts linking smoking to lung cancer, and an ditional 2.4 per cent said that they gave it u1~ because of reports that smokfng has a bad ea on health in generat. In other words, oily 1.6 per cent of inen with a history of ]ar cigarette smoking said tlut they gave the habit be~use of reports relating u ~ ci ette smoking to lung cancer or other . Some condition apparently made se by smoking was given as a reason far pping by 208 (62.5 per cent) of the 333 ac- okera Coughing was the most frequently tioned reason for giving up the habit. Some improvement, such as less coughing, k shortness of breath, etc. was noted by 272 ( 1.7 per cent) of the men as an apparent re- s It of giving up smoking. Of the eu-smokers, 2 6(73.9 per tent) satd that they gained ight when they stopped smoking. .. It is obvious that only a very small per- c~ntage of cigarette smokers have given up tT~e habit consciously and admittedly because o reports linking cigarette smoking to lung neer and other serious diseases. Even if the reported link with lung cancer was a con- ibutory factor in several times as many caxs ai recorded on these questionnaires, it still as relatively unimportant in terms of induo- i=~g cigarette smokers to stop. On the other nd, reports on lung cancer and longevity ay well be a major factor in the remarkable increase in popularity of filter-tip cigarettes hich are advertised as having "less tar and cotine" (p. 2959). That the findings of Hammond and ercy that the many reports linking g cancer and cigarette smoking have apparently induced only a few smokers to give up the habit are probably an accurate estimate of the facts for the general public is drama- tically attested to in a second study. Lawton and Goldman study. These investigators (1958) conducted a sur- vey of 72 internationally renowned lung rancer scientists who attended the American Cancer Society spon- sored conference on lung cancer at Virginia Beach in 1957. Their control group consisted of 72 psychologist- scientists from the Division of Ex- perimental Psychology of the Amer- ican Psychological Association. Both groups were matched for age and sex, and roughly for scientific nature of their interests. Interestingly, the two groups did differ significantly in (a) the per- centage of current cigarette smokers (p <.01, one-third fewer current smokers among the lung cancer scientists), and (b) past incidence of cigarette smoking (p<.05, with one- third more lung cancer scientists hav- ing never smoked). This difference in current and life-long smoking pattern, with more nonsmokers among the lung cancer scientists in contrast to the the behavioral scien- tists, would appear to be an inde- pendent confirmation of Heath's (1958) finding in the 20-year follow- up study of college major and career choices of Harvard smokers and non- smokers described earlier (see Table 5). Lawton and Goldman's next find- ing was not surprising in view of the different areas of specialization in- volved (and thus presumed firsthand familiarity with the scientific liter- ature in each of the two fields) : 83.3% of the lung cancer scientists versus only 63.6% of the psychologist-scien- tists felt that cigarette smoking is a cause of lung cancer (p<.01). When t
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CFJ7LSCTZ.Z1sTiCs OS 5Y0J:1'as 1SD SO\SCOXS:.i - '~a$ TA~•:: (ItAr:9:•AA GI M1nlrl-lz c1iYY';1 SC, CIJt 9Aa:: :IGJ tl•tJtv i N o6T:,1:C I ID-t: =r•~ -- ~\:da i Fa ; e.- . Uot~ i mate m:.> ~ sara ; =~ ee:de ~>rGt l t(~ aZIue e!L)........I -S ~ Lr.3 I 141 o i 1 I 1' Cs ~:PC ~ j!.,S 2.,.. ,,..,,, , yl t L35 ~ 1,14 :: 11 , li i+' Iri .O7 3••~- 5'= ~ lin I L'L' 9 .i I"' Vl ! ial ' 1.l i(low CL.......i 41- i 110 i a57 S ~ 5 ~;i3 I 19 ( 141 ! 1:h1 anmun.. .. i 0' 20 ~20 : _ 0 0; 0 1 9 I:0 i _9 - Totnt......1 220 ~ 60I ~ a'JI ~ 79 ! G:[ i 3'= ~:.R9 i UQR . I majo tp (about 75 pcracnt) of the matchcd Woup cre fe-Iatas. This sex distri utiaa is diffcrcttt front that of the total sar,lp!e b.:causc only aiu,uc s0 l at of female. saioke, whcrn.aa about 75 pereent of mules :-rc / cigsre tc sn:eke:v Coaseyuatlc. it was csix to abtuin a matrhod group of femies than of mslcs- It -ould be Lighlp deairublr to ot:nlpxo all tse u.•ai!ablc ir•fomwtiorn from he sarnple and not fintit it to tnatahed pcirs selec:cd, but r,•mputa• tional tGfitcuhies result if each of thu reapunscs is w anulpzcd. Hat'evcr, such n analysis is being initiated, n;iiizi:tg an cinotion:l scoru nrnip,ded from he respoaus of ail the items. TLc asults n-'lI! Lu reportal u'I.ro compi •taS. Co parson of smokers and nonsmokcrs is prasented as the percent disiri ution of rasponem for each item irn earl• e-svup of quutions tvitL a quaL• 've response. In the stststicnl ansl;-.is uf theeo result4 it was n to take inte account the fac. tilat n-d •.crrr dcaling witit muu•LMl group • The rosponso: of anwkvt, a:.d nur_vnoken Latl to bu crnss- dessi, etl, and the ahiaqu+ru t:at zu;:c~tri bv Coe!ven ior'utaud:,.l Frou was Csed to test atattStlcal sl`Fn'-1(h1llLe (B)• For acample, in a ;t•ca ry reepottsa, smokers and nonsu:oke.ti wore crossela=,ifini as fnlln . . . ' r Sr•nker< , . ' \.cer comstimes Ofteo S.ea NrAaC1ry. $enNt/Otq Often Tte e~ib roatainiagsn xrepresent :•-sponsn in which smokers anil no okers a,r.reod. The pooled crl:- a,-:a_nt.-d by A rapresent smokers Y-- ~ r.aw..r 19a0 7 oozo59p > t TIFL 0305562
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SA1f)XIiRS .dNll NOKPAfpXFRS' Sn~oNso f1aAi4 1>,iud'utR of Iniman siluatlan; tMt is, if --- -~- st tmits uot without vnlue for the TAav a-Arm eJ Cnlleve Atnjn RHmJ iu anc n imngine one persnu posscsscd of ar of t e.c oehtandiug trnits (perhaps a con- fusi g concept) ane can concaire of the pers n utilizing me agaia.t the nther to adva ttage in daling with ollter hun>.vt be• ings. There is ma case in the series which wns ssigncd cdl Eve traits. There is on{y nnet saigtu:d fonrof thene (without thetrait vitnl aRect): he is a very stteceasful b ac v,. i ass sr , nverer, amatrQ. d if d h the Si Twentyone others were aarignal thr of thcse outstmding traits apiece. The 21 i en distributo than.eelves as follows: 05 ,bfS1f,HS6. iin of the outstanding traits aca mu Ily esdusive, or nearly so, and show cnu sting tmuls which strqngly suggest diR tcei in personatity ammng the three types of snsokers and twnamokers. Thua the Il-intcgrated group matafns au eucess of S, wheress the less well-integrtted g.rnt cenains an cxcess of H5. Tha in- artic Inte ar¢ reprtitiental bysn eeceas of OS, herete a group alled "verbal rich- ness" contains a slight estcess of MS and HS. The group chuacterized as shy mn• tains excas of MS. but that chatutetized as ' bla contaim an eccess of HS. The gr with the naitr bland affaet, contains anex affeet Ceai of ess of QS, bet that with the trait, vihal (colorful, rfdt itt eapression), an ex t MS. It is inlernting that a group men assigned 'unstable autotpntid' (pert e anxiety, trmwtoasneu, blushieg Pass ring, Wipitatioq aud other functional oms) had a normd distribution of sm ng habits (P=0.71). A tar clasaifiatites of the mas rccading to " arty sLtbifity' based on ymn of fdil ttp after tnllege, what compared to the MS, and HS ategories, shows an exeee of OS and dfS for the moat stable, and exeess of HS for the least stable (N= 06, P=0.09). Tn nury, a study of a comparison be- tw personality tnits and smoking habits w te that nonsmekers, as a group. pns' f/tutL AroafNyw Na Ni nn0.. Nna,N,Nen<s a L m i..,u,na,IW n T < N~eO ~M1. bMa. 000 IOIIesp,T~ ~ JA ~ P<eM xss the more staMe <ryalitics of dcpend- ability and good d'ttettion of vrns in life, atthough they are somewhit on the biand, colorless side, whereas the smakera appear to cnntain more of the men who are energetie, searching for aims and purposes, and pertnps, although less stbie, more interesting. . Cttefee of Major In Canege Whaf a uaut actually chooses for major in college and what arcer he goes into are more tangible criteria than are traits which are subjectively assigned. TabLe 4 shows a rdatiat between genwral area of r..ajor in college and smeking habif.., The 05 qrmtp shows ut excess of inen dronsiug the natural sciences, the MS and HS gro•tp. Quasa of men choosing social studies and arts or letters. bfora speei8tally, the OS group chose partiadarly chemistry and physics and the US groap, fine aeis, foreign langunaat and social sciences Carsv Ctsofee Only one <arecr area reveals a rehaiaa ship «achbtg significance. Of the 31 men ia seienee and engineering there ia a signifr- ont otcass of nmmmftea. This is ii- lustrated in Table S. Eaesoo of HS were present for secial relations (P=015), education (P=0.40), and writing (P=093). F.xeesrs of MS T.n.t i..(S.n. CH, lotcd tn SnxNnp a.. ~nv Taae T075904 M n 1 N~tn /S rt n PieAt M 91 rt 381 TIlVIN 0000622 - ~-TIFL 0305528 --
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ci:.2ce;sarsztes or dnroxses :aa .o\*s,tos_c:s ?di Stethod af Study 1bc afo-=atio- r.•ss obtaiRp cA edrd: p, an•:, C1S yc 3 of a;c and owr) in ali r: c aatr.p!c of at!d:caac+, ond a nlc of adu!u in iudgin; ir. I'.u:1";2o end IiLnatotr, \e,r York. E'der•ts of hospitals, conrer:c-, ,iar::iu?ci,•;, ctc., axte cot incEcdod in :h ar.mp!e, ead therefore ttot,: in:1 n•prtm.•nted tic nnainsti- tu oaefizedpopulatiou. Inbr.:yc!„_rc;;.dt:::<id:s~esettdlod;;isg!rocaes, th samples were aJected so thce uav rrsui;,•d in an ovc~u1 ~ur.ptiag ctioaof1in15. . - - systemstic samplo of url,Ir,~.:s w-. dnuen front G!:a Bu:falo City Di eeto.y of 1758, supplemr:,;e.: L;. i l:.a of nxu-bt:ltiina er!dre'ses ob •' cd from p,•rmi[s imued by- w,: 3ireun ot Bciidiugp. To ulanw far o' ioaa from tbe direetor}•, [he --Sei.`.oIen in:cn-uY' mcthod, doscribod by Taus (8), was ttud; addre-a:cY t!:ru; obtint t uc: u addal tu ti:c or(~.anl 1is :ndepsndo:tt. araal samptia, ,:urlies Ind;¢;tterL that }er.- tes r.d- dr were atissad by thcsu mer6i.!<. mWhods wcr•- rL4iY: for sr .pIing apartment housn, lin:,aea .t a.'. (;;. 'f•ho s.p?iag of lodging boases was car•'c,+, out ;-mn lists obtnintd front :.he e Couty HealtS AWpartment wherr cavn !udgine boudc is :cListered; a e'.Jatie San[ple of individuals u'rts tlran':: :_-unt thl3liit, 1,'itft 4 9M1m- p g f:.Atton of I[alJ. &ter 4t!':ctiJrt r:'Ls •'an[plLtxd, stLT.ple add.-C.tS{S sr e{u•tane d iato socioewanmi, quand, ot the oity popul.afon as d :ainod frorn census-tt•mx dat:.. ddrfrca•, were amigacd to inter- sie s so that eaaft iatetsiownr ha,l s rrpresectution from ell socio- ec omie stmta. total of 4,4,50 adults was iztcrciewerl. About IJ p,acc¢t of tho sd •s in the ecloeted >,trnplo +ea> m,t interrie%wd for var.ous :vssons. So e refnsed, othora u•ere too ili, ::nd s[itl otl.us could twt tw contacted d ite repeat'ed ettcn:pts by thc i:aa•n-iu~rrn. - aa iafo.-mation can be dicidac 7:to 2 pert:,tieprnding on the me:!,od by which it wus obtained. The fo!]nuing wus uhtaim,t 7rom each ree ndcnt byvtircct intcrrieK: n4e, sex, racc,lifotime marital !:is:or}', ed caGnn, oceupation, lifetimc ro,idencr history, :itetimo smoldng history, his ory of hoapitul'szations, esposum to diabmostic uod ttterrapeutic X rura, at tuda toward smo!dng, and, fro:n eaoh u•oman, a contpiete menstrual an pregnancy historv. An attontpt was madu to.determino the omo- tio ataWU of the respondents by means ef a mult!ple.•soice qucstion- n' , which was hnndad to t1w :espondcut to cScck the approprictc eas er; this compriaed a majar portion of the sce7,nd part of the intereiew.' -T' ehcel- list induded a quntioa on rrliS:ous preferoncr and one on ~ cision (the lattar to be aaswtaed by malee), which a-em consdered too peraoaal to be asked by tho iatx: riewem Also iaduded were scrcrnl q tioas on participation in sports. Ia ;ome instances, beeatae of lan ~a„e or reading di&cultim, these questioas had aobe asked by tho in 'c-3wer, somotimn tided by aa inta.Rreter. - he qtntiom on amot!oaat sLns wera obtained from a list used by S es G af. ia developing a\eu.•opsychiatric Screening 3djcnet (o'). nL ~.. n. f. r.lw.q 196V T0020588 .
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1050 tlisapprnr.'I'bi> briuws its In thn fnrtrth obscrvnlinn qaoted earlier, Iho . tla'crra>c iu iuride.urc of hnt" taulcer in U.use wl+o glvo ap suwkiu~g. (t ) A mnjar Ilit of I:be evldtsun for n demYnse iu rdu ot lany; cinfer iu e.-snrokcra iv iourrd in u Ilritish studyof lloll.qnd Ilill. 11orn is on _: . iutllurl+fut quulu frn+u Iix.IF I1t16Ilu1ttlUn::~f,~a1tp'of Ulo nftmj ILOWAVet•, 'nllu (mstnl un srntdl liuutbwy;-midtaltlwtl~hltltly`mnl, cwntrtbatuuso-;. . fnllytothogcucrnlpictmntbny'cunnutlwrcllalottiitdi0iddr1ly,nThis . stnlewcnt n-ould cartuiuly-npply'to-Ulo debrossed Inng ta+taer rato in oz-sntokels.'1'be //(leaa'('asing f.laff iabesod on 116 detttl,ts from rcligirly dia;,noscd lung auleor oY'syn 1Q-ycar. Pcriudaabjs PPl't.er Of cust~ Is Inwleqnnto to i119ti1'y the S[ntlllleltt"ti+llftresiVntiORrof~nnokil[g leu419i to.:.. _decreasoal rlde of lung canoc'rA 'Evwt if, iu 016 long rnu; onouglt dntn'accmmalnto to support tite nbovo treald--lhetv is still Ito proof that emoking enosts lung I:alurr. 'l'hoso who wcro able to give tip nnoking may'bu constitationslly or bmnornlly di/forcnt-antl so Inay, bdong to the gronp not flastilcetl to tluvolup cmu.•r. Or did a simibtr cJmugo in another babit, ns drillkillg, occur nt t7w timo whett onolring sloppal S 17rnrn is n fairly atrong cor- relotion bctu'txn slunking nud Imnvy tlrinking. Vnrtnus liqumn ouldnin n variety of cmnplos cotnpomtds of unknown au-cinogenicity, nnd sromo Of ChaSrn culn)wultds aev released itum the bot1Y t:hrough tlto Imlg nnd breath. Perhaps n dccruasaf cotlanmption of ltquor may aecottnt for tho decreased t'ate of luns cancor in ec-smokers-plroenming the dectrn.setl rnto is real. lYith thls type of evidenco for'calfsntiolt, then, it would srcm n'nso+rnblo to nwnit tnoto thrta nnd to explore dfangca lit otherhnhiLsnniur.idtsd.witht.honms9tofnnroking- I - - 1n i11a ffool si ftin4 of nvidmtcu for snnikiug as a cnusc of h+ug cvitcur wo lind morlt sug/,natlvo ovidcnco which ann be interptr.ted in a vnriet.y of \rnys'ILr. mufor poitd of the plpponenta co/lccrlte tito cortc{ntiou bctwcmt lmnvy clgarotlo anuking alld lunq enncnr, fo repent, It n lrrnnl; to ~Itcslmm thnt conelfttiat is oquhvltlont lo cnnsu and efcct. As ment.mtcd nbrrve, tloro is yuad em•telntimt•bettroen heavy drinking ' and ci••tttotlo wuokiog. No omlo in his right mintl wollld aavtmte tlmt 'ukeollo~'ism is cnnsed by tanoking mtha' than by a/efdml. Dot1t eondi• ' l t > ti it ' p s ona _const n ions .+n rrvbubly products Of n Llsyclwlogical ol nf n1tnnm- n 1111n1, n9 ccs ur.uc.o....y o,....... .^-• -.• •-_.. -_ _ tivc, lunnnrrnn.untin8 oxpimrntions for much of the ovidence linking slunking to lung cnneer, it is di6foalt to acef:pt the direct entl/~-and- c/fect prunonnconu;nt of otho+'s. in my opinion, one can tatlt only in r1• ' .. - . . . . .. ~. I:. .. . . : . .~ . lor+ns of posribilit7. . . . : ! ho.llachmeulstoDr.Zcitlmnn'set.tomontfoNon:) D•r.t Vnee or l.vma Zoolurr, 8ooln/ h1L1u+V Nmn: alrrch 17 1018, Cumden, Nmr Jerur , )Prrled: 10•vs to F•Unor 6lacper, Doston, Nnc ' (2nldren: Two U.B. Annp: I042--00 1015 1 8cfndqla Afrlury (lullcac: U. of P., 1034-J1-A.If. IJC01cu1 Sahuul: U. 01 1'., lU3i-Il;N.D. - lntcrnshlp: Caoper lluvl•llul, Cu,udeu, Nun Jcrsey-1041-d9 . U.S. Anur: 1'ntboloCtst-101?-10 SIa1t1 lleluu'Imeot uf Pathology, U. Of t'. yfadlcnl Sehool-1011l-1'ruzeut Ia•urc-ot-ehacnec: lrlib Dr. 81,101,13 Wnnnn, Cnocer ltco.erch Dwtilutey ~ Uoalon~ Nnns-103~1 . I!15U-lOLLt Arvalnle Profenmr of I•ntbolaCy : - lUOt Prorescor of l'ntholu,ry PHndpta lnferest Cnucer Research. Problrn.r In metnstaala, ynttlcuhtrll Uw sprend or cAnoer tu t4o lymphatlc eyalcul. lfonrd q;mfUtoo/loar - MenAet of the .lmerican Uonnl ot PntlwloCr-10i7 8ocfcfy nmqOcrsnfyl ruae.lo,aTlCen ~.1. (Jhcunrnl D'nNOn In Wo llueml Adhenlvoaryn ot RpIlhelhA Cells, Caneer ltexcnrrL 1: 360-.780,1047. 2. 1'allun Of 115nlurmdrtnoc to lucrenso the Inrnrlrcuew uf Ncopl;mm.. Co- nutlmtro-Dnlo A. Coman aud Murlon llcCUtcbcou. Cmrttr It,•.ct•nrch 7: Bsa-98G, lutP. t. •t SFmplc llrtbml at NeusnrlnC Ihe Surfn<e Areu of Small Oblect.e at IrrrCu- hq Shnpe. BclcucraBE: t11-2111, 161ff. '4. PJteet of '1S:min'ntura mr lhr abd,nl Adnculvmn:w of Alnthclful CeIU. , Nc[emc 1119: 6U0,1U10. 0. Foelore ARectlnC the Numberr o[ 'rnmur Aletnntrsru. P:y,erh,.vnls nlth a •l'nruplmtt+,blc lfouso'1'mnor. Co-wnhors-alorfou lleCulclu•m• alu1 Dnlu ]t.Cmum,.(OlntrrAesenrcb/a::/G7 UGO,I:EA- 0. 1DC 81C+OMuuco Of Lnn Culdom n+'d IIICh 1'Wnu /unt Oontcnt hr NrvVl.nlIc 7fyuC I:onulNUro-Aubcrt t'. 11c1.uuC nud 11o1c Il. Counn. C;u,cr•r A: 718-721, 1950. 7. 'IIm,rpulnwtu,rr Pi,sanCe o[ 1Lmnr Ccll Nn,4nl1. Co-nnlhar-.luA,me l(. 1hus. ' Cmrccr Arxcnreb IY aq1-78:1,1968. '. (:uuarltesenreptl;sS-EU•100L A,ncrlean A+soclatlou for Cnnttr Iteaenrclr .tenarlrnn Ansoclatlun of l'rtnruluClnlr A IlnclrrloloCl.vts Fellow, Anrurk,n, Asvarl.tlon roe Adr.ncema+rt of [klc+rte Alpha Omeqn Alpha l7cml.er, Nco Yor'k•Afadcrq of :f.denun Aucrlcnn Soclely for Ccl[ lllology ' 1. RJfoclbxnc" of 101: 1q'mpn NWIu nn n tlarrlcr to thr 1'nsvnge of . Pmbolle Tnmor Oen•,. Cwmdhur-loAm,o lt. 1/na. Cnuarr nereureh J.I: '403-I(Cy ]U34 - O.P.Ypedmenlal Sludlcs on tha Sprend o[ Cnncnr' Lt t4c Lyuynml/e 35xlan. , 1t. Absence uf n L7mpboUe Supl'It In Cnrcluomo. Cuaulho,n--Lrndlcy Copelnod mW Shlelda 1Vnrreu. Cuneer 8: J?3-1^-7.11F,sS. 10. Sr1kM,nen[nl Btudlea on tno Snrl:od o[ Cxu[cr et lLC l.nnPl~nllc Syslew, ' . III. n1n'ct t'aenntu.f Tu,nor tA•11 FLnnnll [rom'19rm'nok Duct lo Lrmld, Nodee. (Smrcr Acsenn:6 15t 7J0-i'! 1, 10a;. Il. Immedlnla Possage nf'1L+nur G•11 Uun,oll TArmq;h Ihe 1•Irnr nnQ lUdury, 2ulhon-trulter 7. Camblo nml l}'1111nm 1. C1ur1a Cmrer RrmmALch 0:St4-OIG,1060. 12- thJOSebin: A 11orMw nrAceent A3vutccs. QinrcrAeuarch R; ]zi-IG?, lufil, 13. 3[a7rerrlmentnl 8tndltm on Ihe Surend of tfinrer ht lue lryn;pbatle fialrm. IV. Rennsmdo Sprrnd. Owcar Itrsmrcl, 78: /111-1117, tu..0. 14. Tho flno of Ulrenlalh,C Tao;or lkld. 1. 1'nKaCo of (klls lhrnugh CnPlllorlra.
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264 . - uLtzs:`zCO who rr-rpor.dcA u hocieg o=ora frcq;tcady' ttc.n yoc- pit;nkcn. en rr_srd to tce co^strokcr}, tho e.•ls ca dcdi'~+:ec~ by L'. Cni squara was coslputed es (;' li~!1= Ttte pt•obaai:ir: o.?t:cs (r1-1f) for r:,e1: of thesc tests nrr pr-.scn:od c:ie'.: cach itr•n: ut ndditioa a, et.< pt•:cont r,:• malcheti pailg %r4e:: ri-s;tor.ae: cnna!e:oly sgoe. For t•.ch oi tlu rtr• ponsrs on qUarditath'r icrn:e, t6w ntcen tli:?cn•r.ct•a, +t a:dard rrroc. of rnvnn diQrrenet•s, nad t:rt• prrrr•nt of n,rec•atrnts aro prosent.vl; n t o+t for pair: xrt parCm:aed, a+:d CaP• jrtoba'siiit.: ]crcls at tht~c tests arr atso presentrd for cacl: it.n:. . Emotional SEatm . ' ' A contjmr6ro o( titr n•:Iwia~c: ~,t c:g:uatte +inokrrs ur•d nonsnlokcaz to cacl: quration cnnocruitt;: stauts is prt•ur.ted in tuSlc 4\Cn notr that o-cwkc•s tecrrm si_:;if.r.rd!p dut•rcr.t from nonsmokers in 10 out uf tt,r Sl iku:as nt Peob:l,Il71T Uf or leSs. If 0.03 is uiNt as atc . si'"tiGcenct• Icrr•1, dt? ~rtiUpS •UarRtlln tJ i4Ln%. In aII those at47ti0us innhi,:!t tLt• 2 gronpe .r.-rc ;ie : iie^aat!v d'u7ercnt, ttteres onari6Csa7d1:EM u~m~rscw~[torrr " •'~ tiecotra'uflssL _5 ourour ~_., r attntnpt t.ill be nt:.!r tn daflto- titc tecn:'htcu:utic.'• \n douSt t4crc uc T~1t2 i.-l:apnnra ron?riron oi :y.~<F.••! g: n.~s ~/ rigin::r tMFM+ as.l ,trari4rrr . . . in qaest:ar.nei•s ••a.n..Gna r:C:w ' . QYtit:n+ , , ' Y~re~nt. diaribn. { i erce~; ' ' ~ ' ~tiVncS:-mtwreenC:, n: rc• n hc h . ~ r:rmFsot~ i d.rre. YV !ci- am a a~rerd l . q f I C3Car- l. X04 IprMfwrra, af~1eF cttb i linnl.cn isnd aan.f ~'n~ 1. Dc nu -t•nr fr.•t 1i1.• i smav6inx thinta tcr ac. ; gnnd rraeun'. :' S . ~nmrrirtth•.....•.•.! :2S . Vcryu(tca......... .1 :.0 I i I ~ I bia i f5• -12L'S I ' r 6 I .. -T 11{ 0 . I . tt mt. c n y o . e a Almuxtna.ar••••.••. 3r_: 12T'! <3.: ~70.r 2. Aow eRcn ded it tnato t'. Sou scrs tu hava fcnplm t ll 'S t d 2C.cror.... .•.- - -.:- :90.6- bS1' 7Z3 8orntrtitnn........... Sd tl 31.: f . . . Vnynftcn.......... 11).S S. j. L D&yYneBandsn.<rtnm-- ~. bleenauFbtobotGar.eu: ' " `Jnrnetueas.......... 17 I ' IR 3 ~ . ............. 2b' k. 1.-t .:..\re yott bot4ftedd wi1A
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df• .t• ARCNlV1LS OF INTERNAL ll1iD76lNfi ere pnaeat for business (P=0.40) mtd cine (P=0.36). The distributions of S, MS, and HS wcro apprr.~imnt<ly nvrn Iar (P-0.93) nrnl frrr a ntisuellaneoas up of oernpatiana. In the 1953 questionnaire sclectcd qucs- ons taken front the Stroug Vocntiotul tertst 7ilank wae nuerted. (The Strong 'est has bcen found to he a good predieter areer, larticufarly for a mkklle dan tun:') Of the 25 atrcer questiona cattr red to mtmEting habits, 2 showed rekttioss ips to the txtent that P was less than the 01 grute, and for 2 nehers P wat 0.04. OS group tcndni to dislike the areer f sates mmnager, the MS group to like it P<0.0i). The OS group liked the rareer / aefentilie research worker, and the HS pdisliked it (P<0.01). The careen farmer and also staalistician were liked iHS, dist'dtetl.by HS (P=0.04). Other tds were for OS tn like rhenis4y but o iGslike the cer*.et. nf far.ner, .roror,.tion wyr:r, pdvertisar, judge, manufncturer, and te imnnger and fnr HA to like the areer jutige. The trcnds bear simil,iri4' to for choice of majnr in coikge nnd reer. Armed 9ardees• mat were antung fhe nonsmokers and motlernle stuokers• Tn a smatl group nf 19 mrn poorly adjasted to the armed serviceta therc was a fmalt cterss of non.vnnkcrs. Heavier .mnken tended to be in ex<eaa nmong the mxn who had conbat duty as npptned to thoae who had noncanbat duty. Ysschatype Sanatntonu, cerelsrotnno, w.d viscero- tama, arcording tn the Sheldon Tem(xn, • ment 5rnk,s were crnnpved to snoking habits hut revenled very little (N=243, P= 0D9). The OS grnup was in slight exces.s nmmng the « rebrotonitc (valuing (das); the NiS gro,tp, among the smmmtntnnics (tikine (or action); the HS gmup, an,ong tht vis<crotonia (seeking romfort and pkasttre). Sittee stnoking, as a soaaficd'bral plrnsure," in9uetxed the assignment of t•naes lo the viscerntoeva etfegory, the hmling of au excem of HS here rnn he dts.•mm1e~L Answedae the Questlenn:he The OS ;roap nnawered the 195S qu.s- tionnnire more promptly than did the b(S or 115 gtoups (N=251, P=0.03). Cnnseiendousneof, as a trait of the OS gnxtp gocs very well with sann ot their The tendency in respoct to broneh of . ahu tmitK: btantl, weR-integmted, sciences. rrice dtsring• Wodtl War II was for HS .The a{S group was iueerttxtg.itq and the ehooee ths Mny nnd fnr OS to chaooe HS group was the slowest in attnvering. Nayr or to tettnm m en•dttm hfe Out of 62 men not answerin in four g uswtly fo a speetailnd xienti6c nreaalied mauths thure taetn 33 of the HS men. There the war<Hext). This tendtrocy Is showtt Table 6. h carefully draatt satht of adjustmcnt thc armed servicea showed suggestise ttottehips ta atmeking habita (N=214, =OtM). L•xensea of the huet adjusted was no rcbtion between the fuQews nf.the answers in the returned questinnnaires uul smnking habit.. ' III. Physiologie and Medical Faeton Physiology, viewed in a broad way, ia- Aufas ptrscnality, for human brhivior is the functimting nf body in its en.9rcnmunt. Y:vcu with otu• rul,itivdy enute ntethatls of meuvring and recording physiology we shottkl not be surprised to fiid physiologic diRercnen between sntokers and non- ymokcrs. Out of many comparisons in this area, including smne of ehe medicnl findings pnf. lAt. P.b.,195J TO75905 r~ 0000623 TIFL 0305529
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274 utt-":: z:.t, T.n:S ir•C<r.yrl6.w. fs•:e. \n.• __-_.' .., . ~ Tur_t !L':rv s j• ! ~ 9 : r i - : lt ts : ts Li ' :t: 16 •- ~1-\,raear.x+slaa.:..cw'-.. Detailed ia4.rpteticn s,n pnrtictphiion itu vnriou•t spnct: tc`: obtained since it ws•a thuugLt Utut >ilnr:+ artiritv u'auld ntitet eonatitutioaal di6ert•uce+s• For exuntpL', s hte•a •r•hosA ntblrtn tttuy not bcgin to stnoko betatu:o of pnrtieipntiau in cd:L'tire. ~'uch an ocesrunce vradd su5pr6t that nnnsntokl•ra, au tur z•ha!c, mil'st b.: coustitutianal!p LurJier thnn sLto!:ef.L . . . . . . . uuotnmti:.::. iu tnowods of obtuinin;: tL,. j~prterii.r.fiun Ly$~¢ry&w • tiuata .vcrn utuw•crr.! by i'nv rats tLruueivct r>rrpt• i5 .. sn.r•ll numLrr of in:<tnnc.:.. aia r.,,.;.i.buu,- I/c tL.: i:urn•i.•.crr ur oth.r , cnutix ~.u,c m~•r,otsn• b,.xusr tn inryuire xh¢tlur xntuke:• nrvi p•y~•u;nk•rs airTrr•,! ia tht.- rr•-p••rt. Iu tr61o S, stlokura nud nmuaaukrn in tili: nsn:•.rllr.l _rocp arr rnr::pnr•d wid: n•.rpect to tht•m.•ane um•1d iuoirtaittLy the r.wpo:av>. Rs a nee;otity nf instanccs (S3 te S7 p:•rrvut). res!w:sw;c; rorapl.•u•d it•-n qurxtionneirc tL•cmycicct, tJthou;f!t 4 pt•n•m¢ utoru :In:so:.,i:. r~ rct_::irrc! ss:isu:nrr tt••nn diu stnoksra. T!tufi it is unlik.•!>- t!:nt t!:r in r:~u!t L•nm diLte[ences . A compat•t+tIn of ci;ua:etc ~tuosen nnsl no:ct,::okcn in stwrtn ptrti::?e- .. titin i+pre+ented in tobb.9..t-it{CII 5!:nK. t!IYt, iez youeo,Etl;iQ~qs~•em~d~d"3T pss ~~~eag... ' t.arat~:uteauokr~ti, aad tt:eso.lificrctscos wern stau,ai.ell}• sy,n"'i 1 a.-. nt a pi~n t'~auilicy luvcl of •t)1 or 1r>s. In one oth¢r sport, either. tennisor badr,tiutou, t!:n ditferenco spprvechcd statisti- , eel aienificaeee roith a probnLilite level between .05 and .10. For o.
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1rf~1~S . tt fA-GO 6 TO-:0 ? Su8'J l Totral 91 okcrm in S, at probability leceb of .03 or !es>. TLis dccrcanv from tLu aNa]ablc for comparison. Suni!e.r compad+otn trnre afso madn for nh ryamoSine mttYory, uefiucd s those wLo snokcd I pack or murc a t aaed degree of e3_~t~ttuion, si::c^ ic may ruleert tho sntalL•r nutuLer.. atber in the total >;wup adwuld ::o~ be iatcrpretrQ ns inQiratiu;; u dc- reeularlyJ titete are also preiv!ttcd in tublc 0. Ifere aj,'uin, difivrenc,~ to group, i.e., the 16 ai„Ttifirantly d'uTvrcut itomx ut tha totcl grLup in • etl thts S itcros fer enrh of thry.• :iubgroups. netlter :urthwl rif eeneparutp e:cvkors anrl untutunkcrv was ns,.! fo thn intfividual items. For •arh ite:n, itAUaol'G atld noainluke2Y \onra ee pared in torms of thn dircution of thv- rnspouae. For example, in ts e 4, itom 1, smokers tarr n?o.co: pcrccntu~:n u( "nevt•r" msj:onar+ th n nonstttokors and a higitcr prre,:nt of:utd "rm~ ofton"T' o tfinction of -tha rcvpotsse is twcant tcitat may lie coctsitt.cr.d "nrn- . ro ic." We oan,desibrontt' sxch :t di'.G:renr,• b,•t;ctra stuokers aau tinn- s oL•ees aa boiag "positie. " f f: ic aune::to!ccrs' rc+pur.so for an itcm . is the "neurotic" dircction, i.a, mur,.• thua Utat u( titn imokrn', a'e rau d'gnata this dilIetence aa being "negrtict:" If ttterm is no diUerencc be aosa the 2 groups, we desi;nato this na a"0." In sotne u,stnnca,+, th ro inay be no waaistant pattrrt:, i.t., smr,kers have lcss nf n"ucvt•r" ponao, c.ore of a"aometimc" rce norsu, an,: !.: e of aa'°ahrncs" recpvuac; th tspe may Lo designated as "qcrstioasb!,:." Thew ilroii;nations Lacc beris applied to antokCr•ttoumtokor campuci;ous fur earh iUVU aad an• p ted in table t. lt is nntawur.hp t!tat, fur a rust majority of the , smokers consistentlr respo:ul.KS !n a"uvuro(ic" dirrctiun. This true wis for items in whu•h no ai.^.twruily si;niCu:ettt ttil(crcnrn, in raii poma were iadirated by earlier ane1.'xis. . ron th.eta data it is appareut that tite responses by cigar.ate smokers on tbe yGastions coneerniug .•mulioow status were cunsistently ature "n urotie•" than those of nonsmokers. As mnatiuned ea~rL'cr, thtse quto- diQarentiated snwkerx .ud Conintnktvi wer,.` the Same as for the .05 or lesa. In ln'n.rul• tor Lutlt r•tal.y and Lrary sutoken. tLc itema . stacisticaUy- sigttiGcaot for S out of 16 SI itt•m+, at probobility lrrds .-4 n..x- r. r.Ya,b isso CSAT~fC:S.`.t-Saes 0_ 5~•i~_:5 .:Sn ]O~a~o'~iS neir~ 4r. exe:ia.;~G<::su:arGSyb, T•rrinL rrf'nCMi \n YRI~ : ! }p~4/:!'a Cl..1 r.Yn• pr,4.C<'a•C~fH: I'pCk4t /i'.tSV'i.cM which e.;a:ettc \sa:L,•r in }CA:LnI >GQ 36:-, alnv:a[.Y.Vit aF'<YtriO:" : TOUzo59s - I
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?Q8 LILiZ\•°c2J • TeoGt :: •r~r!pnnn. a s. y,ri.n:: +..•.•1 ~ -r e/ cq:rr8r ueaica er.: n ~ r:~aU_ j 1'errret i ntr.- ~ It QwotiOn .rL -. I 2S. ltr:w ntc. : nn ;~oc h.rtto- ~ ..- .•nrl ny r.aciae ae u7fe[ ~ \ rrnr .............. \uc wry ~dt, o...... I 'a,. i %'nnn,• ntusr..... ..j 7... ?ci•ly uil :SC Gmo...l 1. 1 : :0. llo pon tare m:y pnrtr 1c- i nlar pl:cxiCO1 or heah4. prol4yn' . . l.a....... -• IC 9 \ o.... . .. . .;........ ... .' 7;t. 1 Cndcr.ided.....y ?t a 30. :Ll tar nl )•wt :IqW, ,YCrr:'. u Se:dt4p rhi111 ar a: ntt:wr xiuae nmd ~ ?.i 7 ' $hihecelohty,.,,,,.. ll/ 31. Uu rau u.unll,r like to he I by yatn~il nr to be e•ItL i ' attuepee~~Ie7 ' Rftt4 othrr Itrr,plc...~ c6. a of matehed males iss rrfstivc{T small (?30),. which mtnt be cwtnidcnd im evaluatin; this cnmpariaoo. Of the 31 items, moketa diiferad from non- ~ wa,-Iier, and the prebabtTity t.cels are sbotrn_ , tinfortuaatolp, tbenumbor.: :_ : agreemeats, the chisquaro values Which were computed . as deserihod.. . nTNL( ........ ~ r. y ~ GndefiYrd.•.,../...i 11.1 f• many who would diaegreo with iw uso in the prtsCnt ewntat, but it is or.ly beule used to fadlitatc tlte prenenta:ion of results, end it ahould l,e vibw-cd ae merely inlicatittf; the types of response eicitc.f by the specific questiota For our ptupoxon it i: suflieir.nl to note that oi;+aretle antokera us a grnup n~npondal in a manner difforout from nutumokets. Of interest in thedistribution of items, arrortiino to the percent of respnnaes, in which smokcts and aonsmokcrx :s;rca. This ia prts+cnttvl in table S nhore.re note tbat, in a mejoritc of lhn items, more tban 5t7 percent of the mstched gruups' re•pottses was in a;rcantcnt. • -• Sinae the incidence of luag cat:r.er is higher amonv males tSaa females, it Ru of interest to make eompirisons for maln only. Tlteee results are presented in summary form in tabie 8, together with timila: raults of the total groap to facilitate comnarisoa. in this iable, oafp the percent I
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Vdu,r 7 . . 1pd.•! .tYt'Ct-h' nY t'tlwb].1NY DI56A5R A.\o 111PflNZEC5toS 203 11, and a few Ina in Grcup I I f. \'exrly onc-thinl foll in Group I V; thc rcmaiudrr csltnot hu dcfiuitulq cl:u.ifictl, chicdr hLrause uf Imccrtaintp in rth;lnl to p:lrtutal hietorica " , - r TA.Ltt IV. DCieTIC ~ , 19DKIal'ALCNAYnRL•NIST(CY ATY I I NTICN. K'afltCT wQ ONttt'l' rANL.~.TAI. NICNMY OIULYf TNDM. YIK•Y,RnxpleN\ (YYNNr(NII:NT AXU/nN I NtGW.N N.f. Idrl(u ~ Nt~Nl:N al'tCTI\IT NNAMT I mGnL NAtN I A.•all)N N+/c+ tit'YLl xNM111"Nrxv) I f exlscliw Sttjt l `Y T ' _ ' . + I + / - '1•-- t3t01 t + + tt + + I + utna 36106 . I + + + + I/' + - + + + + i - 51140 - - I + - - t I l310a 11 - - + . + + + ss2.u 37134 ~I - - + .~ }~ - - - - + + +' ~ - 3 V 55139 itl t + - + 51102 ~I + + 11 IV 3.7105 - 37103 ~ rRm Aaa. taL MLt. 17J16. tGSt. TA.La V. TNs RAno or SNnASns n+ \owaxnNr.YS axoMa \1w01uL Sreaw\H OYa-.eD. r1aoNDINr, t'o A•sa:rnNlLiT tn IiYrf.wTE.~slas.t.m/na CDNONANT f1lawAx rOUN-RAY ~ iL'rarrlelLITY lflnwws IaQlfxnk/xLI aetter N tVM}/c+ . NATIU 1 - 74 Ht;Y 60.a .79.2 1.6 it and 111 ti7 i lntenaed~te f0.a ~ 49.6 Lo IV . 129 Lur 41.9 aa.l 0.7 t ' ' Sueh a cl.wifuation may a4n rnn tribute to the further undcntanding of the f susreptible individual. For irotance, bertuse of current concern over a possible ` link between smoking antl <nronan. dise,ise, we have looked into the smokin* h' habUe of the students chusilttNl according to the four-way ¢roupGnp. \Chetets .t 6l per cent of thane in Croup 1-the highly susceptible group-a'ere amokm , and 34) per cent tt•are unnmttl•cn, just the reverse was true Ior those of low sus- ceptibiiity in Grnup I\" (Tublc \l. lu Groups ti and ItI thctc a•cru atw+ut e.rtt numItNrs of sntukcrs ;md iwnsmolcrs The actual nlrtnbcr of smnkarn a.qk,-tcst aud obv..w~.l in s;lrh nf thc four crnut+, fs shu.•'n in T:.hle l'1. When Gmul++ I I and iif are efintiaatal and \I tcith one dn,aeeof freetlum is rtlruland for smo'.cn T ooxosi3
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a 1 L The Collection af Data on Smoking •Ilu nricitml group of Irartir,ilmnts crsn• pri,vnl N>`C ua•n. Tcu of Ihcse Icft tha s1uJr durinC Ihc fniliat ycars and six wcn: klllc ~d , durnt,C lhr uqr, lcaviu3 Iwn hmnlrcd Siffv- twn nxn. Tbrt•c arlQitiurml inru hnd not re- plicd tn rltM<tlntnairrs Ft11AVi<ntly to br lududohaud nnc nmrc wns acduJed (rnm the grnup by the unhtrc nf his !ckctinn aud by IlerVnllhf)• iIiEFKitRitX Sfuwevcr, frwr referred rue, werc inclmtcvl. Tlxse e'cre meu whn 6ad been thnlietl in precisely sinillar wa)., whnsc suh.reqncnt cxrccrs have shmvn ,vnuwl actouplislm+cnt aixi wha havc hccn faithful in follnw•up qncalnn- nnires, 1*or this Innt group of 2$2 mcn thennnunl qtreslwnnairu have httn returned hy Bo$i rns 'tbe nvcngc frq- onrh Ninety Ixr rent of Ihe mcn hnvc returnwl at lu-t4 onc rtnc4rnnanirc cvvey two •et•ars. Durinl,r the iniliat uwiliC'd eknmi,r.riinn io 1938-1942 Ihc smMtin(.r hnbits, mnnng rahcr luabits, were recnrded Ly the fo7lowing taLu- lar sclunic: lnbacm--unnq dnily, varies; cigaroltcs-Q, 1-5. C-ff1. 11-19, 1 Pnck• 2+ paelus per dq: Ix•r day; ci~trs--0•I•2•3•45 par rlay. In'nd• ditinn, the p+ychiatri:ts :urtt olbers ntnrded for many caxca the participants' cntnmcnts abnut 76c- rmuking habils. F~t<It full qucs• tiononirc in ytnrrs snhacqucal to World War If han cnnu.incd tfx: nbovn labulnr aclxme under a acctint un hvaltlt and habits. Tabk I shnrcs lhc nurubcr nf man aoswcr- Ing llx tobacco alucsllnn each year and the per ccnl nf mat uuder caclt c'ncgory of ,<md;inF. 'Phv vcar 1945 is omittetl ber.tusc of Im few rvslvntscs. This was the lasl' year of the nar nd wn+ prcttcrled by a r(uestinn• nairc airtl imuudiatcly follosval by a Atnrrnrgh qucstiarunlre conccrncd with actir- ilipr dnriug thc wnr- T075900 .m TIMN 0000618 ' v. lw/ 1 - >,~ •-'oo fe;3. ~ tI• .k 3( Differences 13clween Smokers and Nonsmokers lAlIX W, MnnN. M.D. M..r Why some men smolce nnd mhen do not has never been adeqtntcly cxplaintvl• The uestion has umrc mcdicJ rckrmrcc nnu• hnt Ixnv-v oru,king h.is hccn ehnwn tn have elttianzhip In lnng cauccr and pussibly to ornnnry dixnrc nnd sirme there /vire Leon ertain tumapeutle indiaatimts for tNe <nn- rol of +mnking. It is at least theoretically trsaible that smnkin; is oftcn a synqaran <iQrt of physiologic or pcrsou9lity tnractcristitr whirh l/xmsclvcs mny iu- ucncc discasc. Thc oppnrttmily hns eeattly mme to explore some datn alrczdy ollectetl in respect to differenees of phy- ique, physialno•, nnd pcrsmaiity bawccn mokcrs anr( unnnmokcrs. This ie a part of larger e(nly of sntokine hsbits. Chnrla . hfeArthur. 1'6,f)„ is nrclurinQ matcriaf raa the stntc .srnsrce ni the psychndy- rnics of nnnkingj nnd Carl G 3ellzcr, h.D., on phyuque of stnolrcrs. The group under Itudy crintprises 252 ollege gnrftdtes, now in the ak%c nmge of 3 to 37 years, most of them married and ttled io a tvidc varicly of ocairntions rou)•hnul tlte country. They at•e numbcrs f the $tutly of tldult Dcvclqxncnt (Grant tudy)? which is a lang-tcnn entdy of I kaal "ttonnap" collc(7o men, who were rst sccn in 19.SS to 1942 nxl have been urtucd by intcrviesr vtd quationnairc to ry the gntlxring of tlte he presanl. Dnrir~, zt~ inquiry into smoking ktbits sns given c samc (kgree of ntuntion ns otlrer aspects f in(ornulinrl nbtabted about these ponf<i- ts• Suhn(ucJ lor txdak%dor Sent 30. 1957. 1Li11meniGtli,wr waf xuerytrltll in pnrt Ly the dnrm 7rduMry Rrreardt Cmmmullar, \~ York. Fran the Suoly of AAoll fk+chyxrmu (Grant tmbr), Irealu, ierWces, IlurraM Wercrslrs•, atkiete, dfaes- PA - 000495 I TIFL 0305524
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mnl ucm.nx,kt•rs in ( ; rnupr I nud IV nnt, • Ilo, diRcn•nt~r ir +icniIll-.nnt :u thc I par t'cut It-\t'I. fn ntlcar wonl+, a Ixcrallcliwi st•om, to c\ia ln4st'm) ILc ~L•prci' of eunrcplil/ilily In luturc ranliur:,.ctdar Ji~.n+c aud Ihc IuLil id .mokiu~. :Itc hl`ht"n JIn.JMRtlnll nl xmnkcra urrnrring in Ihv t;runp w'illr Lighst .uv'cpliliilitc aud Ihc lowt:•t I,rupurliuu of .mukt•n iu the Ica+l auv'clrtildv gr-wqr of ntuJcnt.. \'i. 'Ille 1'M.e+rtnn ~n ~wou:Ms.lm..r.qo IL".u.tus Snpr.rn GM.rcrcn.ltrn.nr.c. ~`Tn IMnM.\n1.b.11'?l'I~,rllnn.lrl' iV 1't"11'MI: IIl'IYM'n[?MUN isn:u. ('~nos.iMV It.\aritr.M..eMftt+.(4~ ' . . . ' ,vW~xhld S~r]evt~ClM] . : . la . Irdi /s . 172 1 Y.xx-waT c.nrr X . - Nxl:.rrlMUfn' n.n+~c+ . 1 ' 71 Iliyh un+ 15• e3r. ./0.6 u~u. ]v f.Rr. Ii 4 II ' 7: ' Imrrnmmii:ur 15 .15.6 .t7 .16 4 III 65 lmrnmdialc !+ .t7.1 .11 .11.V Il' . 1?q L-r SY 63.6 73' - 65.i •%; - 6.8 p a 0.01 T.\.IS: \"I I. . ' /AMYCTAL/I\'IXMRS54~3 )4iKIMi ILtI1rTx rMFyi.ST oM tn'YMTp.]TnrY. .1M`f]T nMnTrIRStl I/lll .'.\/. ',nS. x\r. Fn 1.44 .i 106 t91.7 1t1ti1,4rRnMJtn+ . tld nu.i . Itl? to5..t ~ s~l- ssi n.n+s > p > o.ul ' . . . . \Ce.thcn +ludiad Ih, rcl:cticin+hip of xnlukinl; to thc rviou+ rumJ>nncuts (+f the (rnrr-was• c1:uMifit.uinu tn sLa w'hcrhtr antn(ciug is nasrn•csttr3 with lxairisr • paantal history, with fxnwtirc indiviJunl tmitam or bnth.' Thc main IinJint,: ' n( this uuds'•nwnm tn Lc publi+hal• cui hu mt•titinntrl nlJp hrictly hcrc. ThJ :_i_~~Iertco:uLparnrr.tl h~~pe7tens~rnLuu1 crxrirL~n-cG.L.l~e'uaslill,htcamnnF~uh-.;. JcetsscG'ol-' rMIIUbir+mol.r~t1_w_rtamnn4..yubjeeacw'fio.w~nnnnmokersnc~.T.~~ " Che dilTerntce xw highly elgui6lmnt (p t.0?5) w$on .ub- . jirl+ w'itli ;I f+arenlal hislur}' of dlainile or qtnytinnaLfe h7•Jn:rtrn.rinn were cum. , I4cn+1 .ritll +uLjv'ts n'h.sc p:cruuts were fnr fnnn that divinlcr (1•atd¢ 1'II1. S1'hcn SIII/JlY"I5 \cilh :wd without a hiw/on' of p:ircntxl t•ornlctn' hcart div:ax wcrc cnml,.,Ml• Aly dilTert-n•e tvai mct sit;uiticurt. :1lthunFh it apprcnlrhad the TIFL 0305588
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~bmn b 0011'ne''"" se•sas u^~n w tJ; a, mrwwete is m s v.ra welM naPn Nalrar,mu 43 y N w it os 1d1 P . mark dcgree between the two groups. 0,7s), Iesswdl-integrated (P=0.06)• faek Oot.emdioe Traits of Purpoae And values (P=0.2t), ndturat fa he firnt years of the SLudy, white the torn ern yet in mll<gt, the psychitit:ists d<• (P-056), And practical orl,nniaing (P= 0.51). The five traits which had thc greatwt n u a 6rst attempt at persanolity dcfickMies of HS reprexutatives were ns ela.esi ntion, a list of 26 "oustonding ensits" follows: dP-eottsaious and {ntrospetYive whieh were auigned to persoas whenever cti, les Onfy two of these tnits, when (A=010), well•intc;rntcd (P=0.13), in- pm articulate (P=OAI), shy (P=0.26)• and com r,Nl with smoldng 6ohfu, showed bland affect The terms uacd to refntf ships whieh ttarlt statfsfie+[ con(r designate traits are self•eaplsnatory. T<cuu desxe The uulha<l of comparison is shown such y"less w.Jl-integmted" and "lack of in Tks 2 and 3. purpose And vilues° shoukl not be cau• III d affect is defined as "Tendency tu be sidered evidence of psyehopathobgy. The cnlorl and neutral; plain, undistingulshed, subjects • were all well within nnn.al un . 91ir..tca And emivent+onaL" lnertico- I,yys.lwtogic liut;ts of lxaonaltty, if we de- late ia defincd as "fnnbifity to esprCSS one- fine normal broadly es ehose .vho funceroo self i kent}vaget inability to daaibe thdr welt atd usefully, who arc hcalthy And feelin s And experirnw." The nons,nokets •..gooi., In a mimber of senses: Rood fathera, have fiem assignai these nw n7fes in de cccess good buainessmrn• geod seicntists. tcarkursM mo :md professional pcopla N ough therc were only these two out- Among the OS the excesses arc of the standL tmfb which, when canpared in fdbwingtmit+:well•imelfrated.iturticuhte. smoke and nomnwkun• reachad sig- ni ce, certain of the «maiuing tnite ~ud afhct, end physirnt sdences. The when arrangcd acrosding to eicessa or ~le5ciendn are of the following trnFn: defui cies Iof the nonsmokers (OS) aod verb''f richnss, domimnce of moof, txk of ,~ . yw ~~n () ~~ ~~ ~F puspose aml vnlua, and less well-integnted. teena f trnits whids suggest dilfetetteee of Th~ i°gS~ts that tlro smokers, in ecnerast P Ity. T1wa the five tmifs which to the nmwmokers, may be nuu who have the greatest ex¢vses of US repre- more dilfinultics of adjushncnt but afeo may senteti wenas folluvrs: least sound (Pa• ~'nO1 who are mars c<prasivq perhaps more imnginntive, and vnriebk. Taaa 2-Namneter~ at.iemer Semkrrr, aml For the utoierate unokers (MS) group eaner Sseeknt ChuneNri--e{ by the notable =eenscs in numbers of mcn are "9/ear,AdM' • found for the traits: sdf-eonsciom And . nuwenes intnxpective, shy, vital MfttY, huministiC, •neu a,.,u,,. tww . oe. sts, ns, a:>,l pmgercetic; the notable defidcnciez xre n• w• Ne• found for the tnit, bland affect (pnnically sew NRn m u n N-rn alono, with the possibk axklitimrof the tmita, xn aesu.we a ,u . Pcaat a sa iavticulatc and sensitive affcct). All of the os. * attl.vwsnuevew.rs:llM.tw.kra,wt. IICC ti'.liLs having noGihk cNCCSSes of MS vaPh,.Yr.hwlbYJ.ql.fqvelw. luv. d¢Fr6m.ics of QS And 153. They all dB0 . 1194 Idl, P.A. J9N A. M. A. dRCNlVnS OF fN7ERNA6 DfEUlC6YE mn t war duties: and lesdiug rather quiet Tnwts 7.-Nunnwrkrn, ,tlMrrame Sumie.r• und pro .\s lives. The nonsmokers have the Hratder Smvkeri Chururrnyrd by "r,.rl4WNr- mnre staady depcndahte saa•going r;ualitin; the a ken are the more disfting, eoergetic, im 've, and volatik. A study of values might reveal marked diRerences. Hypo• thetl II Y, it rtsly be usWnCd that an qhicnf moNv of "keeping healthy" would vary in T075903 TEWN 0000621 --- TIFL 0305527
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, s SEOb' RI'.PHESE-tiTiTI~'E3 ( RzroRZ 1 \0.93-1L40 ~ 23 S¢c ~ ~ Z'i'Z$ .36 DEPAET-IE`1TS LjBOR, AND HE3LTS, EDL3CaTI0~i~3~i~ AND WELFAR , L\D RELATED AGENCIES 3PPR0- PRIATION BII.L 1975 7cvc 24, 1974: Coomi «d to the Committee at the WLeie Huuaa en the State of t e iaioa oed ordered to be prieted Mr. FLOODJ from the Committee oa Appropriatioa5, The Committee o explaaation of the - f Departments o the Food and Dru Indian health acti dian education, em Uoited States), Public Broadcas the National Co Natioaa! Labor R including the'Na Safet< and Heal Board, and the Sol 034050 submitted the followiag - REPORT together witft ADDITIONAL PIESP9 LTo actompenr Fi-R 1ib801 Appropriatiana aubmits ths folLowiag report in ccompen~ bill maldag appro riations for the or, and SaSth, Educatlon, aadelfnrs (esttpt Admjaiqtration, the Offiee of Consumer Ageirs, ties, conatruction of Indian health facilities, In- rsfencs health, and assistance to refugeee in the . tion rdomsstie propnms), the Corporation for the Federal Mediation and Concilistion 3eraice, sion on I3brasiea and Jnformstion Science, the latiocs Board, the National ;dadiation Bo.rd, ,al Railtwat} Adjustment Boad, the Occupationei Review Commiasioa, the Rei)toad Ratuemeat iere' and Airmen'a Home. I T00Z0619 ;-? TIFL 0305593
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.'fM~IA'/(!A' .'I ND NONS'A(O.r!<ft$ IIIS ty intdlf{ein, hitt<q aftfrat he Icn n¢t ona sel ck after artatllcr, ustulty e( hi, o,.n wakine. Di uh7 RtGnt Into onvrnliaoat svdd life; oantv Io nRairs. Di/OCnity cuntroifing drinkhm.. 6tns at I raunl a sclisfecmry esreer m ui,i<h hr wpr f wilh nimat detpen'e etergy. srz 4.-A rdwt nxrgetie Itcethlnmg fdlmr. who bruke f'ram kis cmnemtire fnmilY nhile in teNt . 1014 it110 hmWlt, hCf(ormed imMllsiR nets, atul ,Itne.at was a Imdtlem to Family and rnlleFe. ZYte Mychiatrht nllkd h-nn an irregdir atd imy taunfie boy." In Iris junior yese he had a "ra,r nngqueue o( kbars" ,utd beexue a I(o•1 atml t. lfa vms tamlmlekr et a cmrtbat tmit o( 250 nem dnrlug the vr.rr. Sinee Itwt he h.is heot ane tie,rHnrnl<o(rndnl refaenMarvladiVelT ns Itis idav itun eHtet Mndenua tnvriiee difi-. culli S.-In oallags deaabd as n"gr•ad-lao(c- ittlt feeeuertm6atlJelfeAor." Oneof the few wkll bnnn nnrkt. His onllier snld "He qivrs hirt lo a nw, ide. sud fnll. in love with n new girl ry dq.' Iaairig the war wSS a nami n0iar in bat flfs work remrirn trard in fereign ctwm rin •vd ecasiderWle inftLitiva and phtakal ad' 'ty. Mardeqe resulted in divoree. ece is no ouatien ttmt these five neclt hav# aomethinR in common. They dww seeking for danger, rmllesncs, aud it of itrdependevee which kceyas them acti y eltgngcd its some enterprise which app Ws. They are intetesting nxn who Per- f t useful work. They seam to be wel[ sex but they have had difficulties with I iagc, perhaps stetttming frons their io- Ik edent aatures. Their smtJdng to ezccss e to he a syrtrpton trf their dTeat rest- lea randnm atnple of S of the $f non- ,amkea was hken, atsd their brief erso are a follows: Pfne NnrrutaFetr e 6-06Wncd perltaps the higlnet. Atuty s won of the stodr. Puhlk sehonl uut jtitWle 'N Yefegtoasl. Parents both died wlun he .vo 7oen attd he was raifed by an older sixnr who him good teeteily Imder the dremnata,uxit. lie s quickly to tinests Let atunts to nnrntai q' IX SRdnGud nunmttOst dudes during the was His {utdleeumt qualities are reeos+eud by eud s, its which he Is iuersadngfy, tuaeufnl. Dc ed, csrtuf, and intelkcelet ie all his niFafr.s; has braad geaso of erans nraund hiah a 7•-Slfs wung man wme frern . faor0y of vhty modat menra an( bigh smnAaMS in rhr: Nm/1h - Middia Wmt lle put hmaav)t qhrnnuh cullt:z ,x, tdmiareWW mul by worklnC. Itis (ield it, phyrinl seienee was cJn.en in Ynmh and pununi wlm,mt quatimt tn Ihe prun% snA in a vcry sutiiLutorl mmmee. NM athlede he h:ul troddt•" iu coeiolielnr whart in edmJ, I(e ie a man of reetdzr WUu and devpted to his w.nk, with rather liinitn( inteteects oWSik of Ihis wnrk. 'Ihere Inve Im, a fer ainnr myclum,nvlie rrn'uaka cmmeclcd aPh inter0eranN minlions at his loh. lie Il:ts httn threwd in de.ekry.ng Iris rnrtler. I(e is cnmfnrtahly nurrird. Cue &-A brilliant youne mae fran Ilhe Sfiddfa Wot who I. Mw,ing a aciemiec carcer. lte Iua taund it dl0ieult m laeue himxlf in n nirnMc 6ranth c( hif fidd M nark More +hnn llq ~nutJ mtmbCr of illnVas. A sYCStss(ut (nmily rnam C~ e: Tall, nntNl4ave, CIeI NllnpatCl,l nun of science frmn a hame in the N(iddk West in which same of the patriarchal autonu o[ Lrnrope have betn hatrla( dcwn. He h.u bevt Warnugh ud qttenmfe In pianning the hfghsat geeda of training ha his eehL Ilaa had Irmdtk dechGng between Geie research alvl slmlied edente Mtt at length hu fmmd a good emnpromise Happily married md devete! to both his own oad his wife's yarante A qtdet leader. -GSS t0.-'I1tls -'ams tnn ;xma trom ar sqri- cultmal onlmunEty in the Middle West, of uprishl url strict tnrenu. Since diiWheed fe dw.nd evidence of mnF(ming cvery job with great de- tem,kqliou. HN "mema( alame» is uass ot cviteral altafneneeL.." Lsmo.ge albtM dusing the war. See.dy pta,mtiarn in his work, which is a Eahl• of husiness Ha(qily Imnfed Fritnd(y. aiergette, depaWabN. It Iappats that each of the five nom smoken, chotett at ranrklm, ctxncs from the Mickile-West whereas all, of the heavy stttoken are from the Pastont 5eabtard. Of the whole gnxtp of 51 nron who never vntoked, 19 camc from the XitkEk West, 26 frvwa the Pastera St.itea, 5(rom the West, and I from the South. The geo- graphieal factor may be partly an artifact because of college atLnissitnv Iwlicies and other f,xtors, and it ulay, contribute a cultural influence towarda nonstnnking, such a.e stricter Qodes of eondtnl • It is evident that the brief case deserip- tions of the Fre nonnmokers are En quite uuarEted cnntrv.t to thosc of,the five heavy netukers. The nonsnrokers are steady, do- ptndnWe, and hard worken, with stable marrinhres, histories of specialized, non- T075902 ary T1MN 0000620 TIFL 0305526
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r ^9)6 THo~t:YJ l. y N 195ul , I abovo), the snud:cn prMomiuatc. Thls is especially trueforrhu63 hqpercholes- ; ten-nnic subjects, 61.5 per cent of whom were smokers. Usin* 25D mg• yer 1(A1 cc. : as the cutting point for "lnw•er" versus "higher•' choiestcrol levels, ue have com- ~ ptral the cx(rLrtL.f altd obxrvetl number of smoken and nousmoken-in this four- ~ (oW tablcandl fiutl that the assuciation between the habit of smokioK and higher ~, cholasterul levels is significant at the 2{x:r etut level (Table Xf). Our data do ~ not indimtcwhclhcrsmokiuFiucrettses theluvel of cholestcrcl or whetherstudents I with higher Ohnlesterol levels are morc likely to smoke. However, the fact that ( the pan.•ntal historid of smokers and nonsmokcn are not just alike leaves open I the prwibility that differencus in indivnlunl traits may be genetic iu origin, at ~ I©st in (t.ut. . Tsu X. Cxseestnu: or S>.uwxxs .wn ~~+xeauxexa 67 Eatx Cxntssn:xw. tr..zi. xlnxr]r CHOLY.tPIYf1L llLltL ( svoccss N 264) vmaunxews (.r~ 2d1) (YO. .i) (' Gr) ) ~ t 200 {j.{ 33.6 200-L'1 47.5 52•5 r 275-_'i9 47.7 $2.3 2so-Ha 55.7 l{.7 ~ o vsn 33.0 - 45.0 h jolli 62.5 37.3 TnsLU :U- Cuxrt~xrn,.v nr Skacv CtnwstuMn>. Lsvttu nt Sfwcsu.LVa \~xa.msss I llrnxRrl xnVfLnxeY! xwxvarcxrn.rs. (v. 264) (x- 25.) rxsnt. La~st (s«L',:1 • ows- cxv- • nss- I so. Cn,ter 250 - ( 149 1 161.6 I 170 I. ISJ.1 Id0 nr.al.ne 115 102.4 1 111 I 99.6 . Xi-5.2 0~Q02 ~ . . , ~i ~ j S j il r ~ . The ultimate siunificanre of our own observations in terms of prevalence of ~mn3fovuscular dismse among the various groupe of sttbjeets studied must amatt r follnw--up studirs over the years to conte. However, reports of other prospective : . studies Iwv the a,unc•cuimt of multiple (uctors with later diaense, using older sub. ~ . jectti nhscrncd for scvcral years, arc now bLginninY to nppav.'• This year the ~ Fmmin);ham Study grrntp published findinge basL.tott the fint t.year follox-up % of their caniin.axtdar survey of n cross sertion of the Frnmingham population : who were a/;t.l Jf1 to 69 yatrs on cntcring the etudyJ^ Thcy found signiBrmlt ~ statistic:d am+xiatinns Letwcen high bLxxl prLxsurc,• excusnive wciwhr alHl%or hiSh chuksterol levcls, and an inrrca:vd inciulcnce of suh,,aluent rnronars-he,trt ,' • WnnMe ohnnN. r euwlnnn., anl .M.nw ar ner ~eWwI rllp Gr~.ar.e lran alr.r. , ~ a~~osls TIFL 0305590
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C S.W'OKGRS AND .VONSNOR1iRS va nea of food ItlLtke for each mmt enuld be ub . No de6uite rehtionshipa between habits and dnily iuCc<liat of rip (P-0.6F3), fat (P=OAB), protein =0.36), or crbohydrate (P=0.51) were However, for each of these faemrs tarire smokers tended tm mmane the t k ataa,na ha hearier smakers cawunted more sugar (PG0.0S) durine colfeRac This 4 y associated with a largcr wffee in- iiu'gettce (P>•020). Coffee drinking after egc is positively related to stnoldng (P< 1). Aleohal'indulgence is mther closely red, after coikge, to .nnolong habits <0.01). Candy etting was about equal the three kinds of smokets, Such Ctnd- suggeat cotnmon habit fonnations whirh mi~ht depend for their natere upon asEtat the ea ronment has to o$en Wefshe e might e:cpe:ct that the heavier smoken Id be the anes ~.Iw would gain more weight beraux of Lhe exidenst::, of car!ier sutnptlon of more alorieaOver the rs, howerer, it is the hewfer smnken tended to tote weight. Shs moderate :an had atnang thsm the mnst weight en, and the nensu.okvs Iail an m.<ms osewhose a2ight stayed abouttha ssne 0.05). We hsee nu «tiabte Rgur,y food =,umpffon efaer eafeg., and so no conetuiions as to a rdatfoaabip heewean ta muke astd mmEdnt at this time aa fx mad' Tfts yltt ot mlgltt of sncn who smd.ing has been studied by Rrasek Keya• Slappsenis )7asmL Ottm ougtt smoking is oonttttcnfy ontait[ ere to be a`narvova habR," certnin data do~ifet enn/irm that it»prewitm.t DurinF inttiN axdiql wetmhmtiot considerabfe A hmddowe of Ow esaspt of °ner.os<' or e is ncMel ARhwsh the darem ot stmu ender atm den net hem shmr relations to itec it >.af hamt 'v the previeum t<ctlas Ip Isary'sttqkvs ten6 to pare etmdnuun dri.p m . nsueamea, ete, wh&h mi>dtt he ee'uidered Rereot kb.l at 'Siotvauneu" 'a,re was talnit to obinin infomtation abmtt the kinds and qualitita nf symptoans which young tncn shrw mder streas. (The ttnn- ntan strssecn vaperienad were particularly rxaminations, atlektic gamee, oral rceiL.- lions. and social oceasions, and symptonta werc especially anticpatory ones.) The syntptoms vaperienced were the cnnwwtt functional ratn of palpitation, easy perapir• inG and gastrointestinal or, urinary symp- tauro- insmmnia, hodaches, nail biting, freeryent colds, hettseerhoids, and other ,,mmtoms that might be 'assodated with nervamness under tension were also ran- sidcred. Note was made of the degree uf +ppreheasiott whids ms shown when blood was taken frnm the arm by veaiptmcture. The fpifowing list is of faetcrs whidc were compared with the OS, MS and HS ate- p,oriea, with their P vaItte.. Ftataancy of udtrti4 P <¢Of Oiarehea tt2B Reiettrit>' of be.d mevmemt 0.12 trretaenn• cf heMet ne.etnnt o.sa ran,titatiw nav 7.nuof appetitc u eamet LL75 Haaon•hoids 0.70 OrsuautesW.l tract hridbilitr ' 024 Ciratrtm7 awnntes,s 0.9i De¢tn of shus anhYtamia M19T lknsatosraphiw 0.75 Nal 6iUag 0A7 Rnct;w to.enipweuue OA0 hnema aeo Frequenq of heafrcho 016 fGatorp of har fsrer or a.unaa 033 flreualf fmlyment of .nb{W7 of aManamie netvatl spkaa 0.7t Only one of the itelns showed a rclation- shi0 whidn muld reasomably aceur other than hy cluutcG That item is freqttency of uritm tion under str ss. The figure of P<0.01 is ntostly duc, however, to only one u0 in a 3X3 tablu. Out of an expccted number af tO nonsmokers only 1 had nwderate to n6irked frcquettcy under seress. The rt- maindcr of the table is not suggestive; in fat•t the hetvier smoken • had about the c<pated tlistributinn vuong the three factors at fnquenev of urination which were to+ted. T075908 ~ TIl1IN 0000626 TIPL 0305532
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r 202. Tnt u1.t:1 T v.ev: »s '. i atr,tsiou, i< ntueh nroru frLr(uent among the oBspring of parcuts with eorounry' ' dislr.l.c than cnnoug tlul.rc uith unrotal luuunts.r In thu cutirc 6roup of h}per• . cholcsten:mic aulduuta, 32 fxr rrnt had a parcnt with curouarc discux in con- , trtat to 12 Ixr ccnt of tltrnc tciih nurmalcholtroG:rol values-a highly signihr.utt , statiulical dilTerence. It aplxars, then, that ptssitivu parental historc and posi- tivc intlititlu:A traits often go Icmtl iu hatul. ' , We have rtrocntl)' a(L•st'rihcd a nea• four-w;ty `muping of heatlth.` subjects 'atrortlinl; to bntk purental history and individual charteteristits.` This cLzssi• ' titSUiou is prn(nlx.l as thc bnainfnr seleetion of highly sltsceptible il,dividuats . in teatinl; pretwntive Inr•n.ures at;tinst hylxrtension nntl eoronary heart diee:LSe. The four-way Itroupin4 is shoteu iu Table I f t. "Group I, where both the parental attl intlLyitlual (aattrs are pcoitivc, at:ulds in sharp contr.ut to Group t\', where . both thca'e siy;nilit•ant farturs are u.getive. Thenc two groups are e.e(k•tte6 to prntluce the highest and lowest atL•tek nttt•a respLctively. lu Group 11, where , famil'ctl antf iutliviQtutl [Artun are tliacortl,ittt. the izvmtt may devclop disease , later, thus tr.ut:(urmiul; a Group I I iutn tt Group I suhject, or the traits may be ' inherital as rta•uafves. or the tr.lits may be Jue to cnvinlumental factors. Group ~ IIt, also dixon4tnt, iucludt•n those who have est'apt•tl an atlverx inhcritunce, ' thosn who are healthy carriers of rLctvive trtits, and those who may develop ' positive tr.tits at a later time. Group I provitles subjtrts most suitable for tests _ of prevencive nt<:Isures.' TAlLe IIL FM:II•wAY GMUCYI]O rN IICAITNt' $L'DJY.R1 AS A AAf15 7.4 PNLtTirTri9 \I1A9:1R1 i • AG\IY3THlreeteVY1UF(H}) A8D/UeCtIMI~'AYl Hr_t.rDtseASe(C}) 'J14\irltA%T r.Kn1M! ' l'JUH'F - i - FXnlABILIT'OYOet4LOel]O ' eAMY\S.IL IYn1V'IrIkAL Ct3eA5K 14F/ea' TIIAITn _ , Hqth Fatriy h1yM1 Unuhtful Law •ms?ns Inu. ]Ld. ttJYJ. It4iT. Tnbk 1%, gi.rs some illustrative eaamplLy o( subjvcts front the four groups. "The ptlsitive traits apta•ar in varying rumbinatinns in di(Tcrerlt individuals. The likcliht..1 that a singlu Iw.niti.e chanctvristic muy be fortuitous or have little mtamhlg in ternn of life eµwet:mcy has Ietl «s to phu•e ptTsons shotcing such au ipnland Ir.it itl the'nrgative tr.lit' grotq». The rehttive size of each group dct'r'ml4 ulxrll such tletcrntinants us thc agv of pnrcnts auld the arflitr.ln. limits rhtar:u in dc8ning ;t; 'troFit ivc' and 'm$ativr' trtit: which artunlly van' rontin- unnnlr. 1'siug, dcfinitinna ruu.i;tent Wit)t those prLV'iuu>Ip puhliaherI, wc• have (nun/t, .1(ter ri-viewing thp lindir.g» an 5.4 stttJentn in a•cen col:r.vvti.e that .dwwt imc-aivh uf thr <ui.j:ct+ (:dl in Group I, a einlilar numt>:r in Group 7 002U612 TIFL 0305586
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t.L..r- \rtl.-J .uYECTS UY CUKUS.\KY Dtat\YF .\XD 1Il"l'F:Q7Z'\.alUti . IIM) TletY I. CAee%T.LL 1IYILK1eYNY% A%aAue Ca4\VAY1't)1l4fF aQO%G 724 J.W%Y /h,l•GI%p MKY1Gl SILIKYft • 193L-19S1 1955-1959 '. TntLL x'Yl~l . . ' % ~ 333 x - 371 . % - 711 •rl'aRin a[p,KTL\1i . . . . I %0. 1 :e a SO. .. . a Isusnt: dath lmm thu.v cau.ea y7 7.9 . A txuent with uvtte 6i.mae (atrake. caro-' 26 : 7.i ' 2i ~ 6.7 - 31 ` 7.0 mr) oeduwon. hrart failure) A Ipnnt with nwdunt. 6taeey (uesina 16 4.3 ~10 .. 2.T 26 3.6 ' peeroris, enlaruad henn. etc) ' A rytent w(thmiW hpp.rttnwnn 1 24 6.6 -. ; 32 1 D.6 i 56 ' 7.7 Total with Psidle purentnl hi.tory ~ 9! I 26.3 i 9: i 26.1 i 190 '` 26.2- Hopkins Schooi o( \It:dicine, using thc medical scudents Iw sui>jats.r? Based ou the h)-pothirois that eaeltei:d hypertension ulul eortmury• hatrt diseusc aro +suo. . ciated disorders in which multiple factors PhtS a determining roie, the incestil;n- - tion w:•u for the purptme of seeking out factors which may be of \;liueio the,pred•ution and pruvention of such so.callatl •'deguncr.tticc" eaetlie.asntfar disr.tse- ' Thex factors were thought to include constitutionul differeut•es txisnf on genetic. - inheritwttro which may be itientified before the estnhlishment of clinicJ diseasc. . Accordingly, we undertook to study the occurrence• nature• nnd intcrrelntianship . of tt variety'of gcnctic, physiologic, psycholn,•n: ~, aud mctuhofir chnntctcristics ot - yotntQ adults und by follow.up studi" to determine which traits arn emm,t (re- y quently asenA-ttl.d with e:trly onset of disease. The evtct furm of elis.:uu andd age of onset in a giveu individual were thouyht to depeud upon the nature nn/l - num6er of the factors in his own ganetic inhcrftmtca in eotttbination with the particuhtr environmental strt:ires enc•nutttcred as he gees through life. The possibilitinl opeual up by such an apprrKtch were CvsL and ufter eleven yr.ln of pursuing some of them, it may- be saitl that we %cem to be engagml in more of a r(.ewis:utd Clurk expedition than an orthaha eqridemiologic study! . Fnt, t shall show.some results of the fDmily-studiex U ith the :ISSisr.mce of ,' the stuefenes themselves• Ire have obtuined dutailetl information c/xlcerning the ,- oceurrence of hy'pertensintt and coratary di+l•:u..:ts well as d'ett7etes :uul obesit.v• atttong their gruldparetrcs, aunas• uncltss. antl-mlat impnrcalrt of :Ill-thelr - - . pnrenta.• - Table i gives the epcetrum of p•rrayteul lty7xrtenaiun mld coroilary• - . dise:tse as reportal by the students while in tnetliral school. The purenta were -` .; . almost all between 45 aud 64 yr.en eld, at a meon ageof about 57 years for father» =and 53 yvus for mothetx~. Thepnrental history isshowrt hare for two groupaof =°-- -' sttKlencs^ the findings reported (ur the early ctassea (t9,*8~y97-t) have alrend,.--: : beeD publishal: thtqe for the cl.•tswls of 1955.1959 are very similar.' 1Chcn thc r~ - tNogruu(narecombinLrl,th¢ajtectromprnvitletfbythepare.ntalhistory m:..-bc . . tuntm:lrizetl :es follows: - . ' . - . .. . 1.' aninng 724 subjects whnsl: pannmt history is knnwn• 39n. or 26 per cent, hcul at Ic:mt one parent with detinitc hyperteKsion or c•nmmtn• dix.tse.- . T oozosos TIFL 0305583
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A.Yt'L'CTS OF CuR4.l'.\kY Di56,\Sa A\D H\'PfikTLYStOR 207 \.w4r i disr,ue. Most impurt:utt. the use of three facton in combination-bfootl pres- sure, relative weight, and serum cholnterol-permitte<I the separation of their subjects into groups with highly divergent risks oT coronary diseuse. The inci• dence of new disease w;u L43 per 1.000 in men with two or more positive trsits . as opposed to 10 per I,000 for those without any of the three traits. At the s:utte time, groups from Albany and Los Attgelp reported on cardiovascular population studies with followwp informatiat for periods of lesm than three cears.iO.O• The Alb:uty group faund nearly six tih+es us much coronary dise.ue appearing in thox with initial cholesterol levels of 273 mg. per 100 c.c. or over, as opposed to those with initial levels of less than 200 mg. per 100 c.c. Also, those with gross ovenveight, w'ell•marked weight g.tin from the aye of 23 on, or abnormaL eletEeocardiognms deveioped coronary disease two or three times as often as those who did not. The interaction of these fcutors was not analyzed- The Los Angeles group found a higher incidence of wronary disease among men 40 to 54 years old with higher relative weight or higher systolic pressure or higher diastollio pressure to begin with than among tnen of similar age without these attributes, but the positive associations no longer held in those over the age of 53. Nothing was said in two of these studies about the sigttf6caace of a positive family history of hypertension or coronary disease. In the Albany report it - was statad that "a family history of vascular disease. .. failed to show sigttificant associations with ixhemic heart disease;" but the particulam were not Viven• However, in a recent analysis of the prognostiovalue of life insurance mortality investig,ttions, Bolt and Lew brought forward the importance of a family history of cardiovaicular-renal disease.'t For the Rnt time, studies were made an a group of 11,600 insurance applicants who reported two or more cases of cardiovascular- renal disease occurring in persons under the age of 60 in the immediate family as compared with standard risks. Over a t5-yenr period: thase applicants, abed 30 through 64, whose family history was marked by early cardiovascular disaaae, _sufieretl from 1.4 times ns many deaths as did the standard risks. The group with positive history "was characterized by an exeees mortality from raraio- vaaeular•renal conditions; in the aligregate the death nte from these nuses ems .. . nearly double that for standasd risks and accounted for meat of the eccesa mor- ~: tallity.' A supplementary study showed: "among insured persons who, in . addition to having reported a family history-of earlyctrdievasculnr-renal disease, . . Ieitherwereslightly overweight or had a slight elevation in blood prrssure, deaths .. j. were 1.7 times those among standard risks, whert;ts, among those reporting a family history of early cardiovascular-rettal' disease but free from thesr impair-. meats, deaths were only 1.25 tiines thase among standard risks. The dit7ere+\ce ' ('between 1.T and 1.23 may seem smail, but statistically it is signiticaut .... ^.. Insofar as ihese 8gures go. they indicate that a combination of a family history- •" of early cudiovascular disease together with conditions associated with aardio- i vaxular disease, such as excessive weight or hypertension, is of much greaeer consequettca than chese associated conditions alone." Cholesterol levels were nnt includcd itmtheir studics. . . . 1Pith alt these facts before ua, it is evident that the long Rnt step has 1xti•tt . taken. In yenentl, we now rnow who the hiyhly susaeptible candidates for caro-
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L ) and with the sandanl dCwiatinn of T^Wr cient of varnttnn of the tidal sir (P= o,a.a„e ! u ti t rnn 'mnpnrluan of 1J5, MS, aud HS with the a~..a n a a :1. lf. A. ARCftfY1S.1 OFlNTtiRNAL llF,OIC•1NU TAna 9.--Addewdd RrRrse. arRcfold to Sowtine ffabitt 6n wetl wnnh invcaRating- ,tac..W a.ya. awr, > na ve. nxr<. dil urad. ~naWh phyvlulogy, that ix, a dlf- f nt Aow of salica atul u+ote npid a~ivtlry rc . of the nnnloers, ia a puint W+iett wnudd ti<btl air (P-0.37) nre not consistont• tetulatcy is for hrnviernnnkers to hnve renriability in the depth ne respirationa esti+r.ttruy rate and ti4+l aie are afae ted to outstanding tnib. Thua, ataw, theta aea in aara auwng the folletw trxit fra+pe: pragmatic, humanistia ttnl, ntul pru.tial organiaiug. ILipfd then aro in excem amonR the following t grotq+s: shy. ideational, tcsa welt-iato 1, nnd aaocial. Again we mny be ing with crnntelLitione of tnib atd nloRical futtNiana. with smohing habits t of the oonetellalionx Crequettt sighs swalbws also wtd to relate themssfves ayain tn(is h, the expeetttl fanhien. e secros to be an n9atiooaltip between iratory rate and pitq emnfdng. The ro diderc+tces n¢ur betwecn itonwnelesn cigarette snakcrs. Fipe smokers, as a do not inbale, sach annlinq heing more nuth, lipa, and tongue artivity'than one hieg the hmR... Redsa a were recorded (IuritK the ph aied e.•uwkatiat on a thraefofd acale aed) for fms- .(n _.. .---3o ftl/,detn tr s ~ ~ ~. ~ . ~ wy. atd~e'i .w.q,ee ~ NIQ. Of!! Whan a ntatt had actiec knc jaks Vaualtr ]ad aeCvr eeQ•tites ehmwlwe, tha was uet alorays trem Ltdt of the x(teatn thowed sim7ee rekuionships- anckinp hobita, but the rt•Iationship was re fnonouucul for the abdominal (Table 9).* Ttq abkwiml rAM was ubWrcd by saatd+- Ike fow mwlrnnu with tha IAsrp t+aet of n kn apdkatue te ran of dixranotwo he- pnx awl Io•.v nltetet an averape was at Active tl.teninnl te0eao often occurred in fhe ioon: tieMWh mbjmes• Aeeeam whid+ re- Sfqt cut teinln.ae.nene le dtafn th wen FWmk.t ftllQafL . ... ~de4eYMr • Ttr neneweH..Er..w ueutn.a er x.wtm. u. at. pnFUnt. auT tL.al.rp pn~M c/ a awl,a yiM19Yr. f~ Mfs af JYn.nrntl 41N.n rq,w xe ~n.w n4w. en aar.r. rb n}nMl ~Mp~~.C..,~ W WMht1X~,a~iunn Wtna M n~ N,aOtpb INVY wM WIWNY ayVMaw~1' M~n~~~' The table shars that abdominal ydk•<es t[rpl •to be intReased fnr nononokera+ tk- crmsed or nonnnl for the smoken. The mme tendency esiafs for the bi k (P=0.05), ank/¢ jerk (P=0.07), anl nee jerk (P=d19). It seanx tmhkety that niCx- tine ingts["qn or other etTecUc of unnking «wkt can.o reduction of n0exer, which were tested during cnllage when amnkinF hnbits had eot been fully atablished. Tlhereare olso snmc intere.ating diffettmlce9 {it ouotanding traits for fuat atnwifyt Nn varima tyres nf .e/lexes. Mot with ie- cretuet ntkacM tmrl to hxvc traite stldt a.a wdt•intearated (P=0.02)• shy (P=0.0S), inartim!«c (P=0.10). bhnd afFrct (P= 0.17), physical sciaxe (P=035), whfeh ue nmtly those cnnunon for txmanxikcts U we group normal antl diminished relkmx tngether, eaeesxa aru present for the trtits vit.i affect (P=0.11), lack of puqtose and nkes (PrOtTZ), and kss well•integrawl (P-0.07). ~ Thele ie nla9 R moderate n:(ltlon9hip detaonsMbtc between a6danrfmt neesa and rppiratory rntea (Pmg,p5)r those with waeased «fitxes tendSn` fo be'aBwer breetherx, thnse with nomal or decce•t.ed rNkxo tending to be more rapid beeothers. No clear relntioteship of a liks kiud wasohserred, hewzvc, bLLweea the olher re- Nc:es a+ul respiratory r,ua. 7f,tllac and adefdnc xtlifs Whm+ the harficipants were in +vllege, a carcfuf dict.iry history was ol%ainal. Mewurrntents of the acrrings were m.utc in eotk•ge dorenitorics so that the tclativc ..- YaL 10f:Pehi ID56 TQ75.907 ialviN 0000625 TIFL 0305531
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\..L... r Anl•F'.IT511t'ruM.rX\P1 Itlvh:.lali.UUI111Y114:\.bl\ . pli i pvt.rnl h-rcl ITahl.• \'IIIL It >hould Lc rt•rall..l hcru th:tt Ihc iuc:ut aKC nf iht•v lart•nl. tcn+:IL.mI ii c..lrn. .\trnnlfnglc, a largc hropurtiuu of the 6uher: .1nJ tnulhva Jtytiucll Lu dccdup hvPrnonilNl uf thc /IiuNtulil• tcpc havc alnudy d.nlc w/ u'hcrt•:IY tuany uf thc Guhrrr und alluuNt :tll uf thc luuthvrY wllu, t.ill IAtinvu.dy huev, tvnNtnry hcart Ji.avv an: +till iu pINNt Lr.tlth. Then w,n uu~ru nnu.uwkcrY nud it•wcr rq;nlar Ymn1a•n th:u, mIN,tu+l :unung Ihlr suhjtct+ ulu+Yc Ixlrent+:trc Iwth cntircly fr.v (nnn Ityp.rttvl+iuu :utJ curalwry hr•trt Ji...-1w• :1. - co1nlTlnrL IXitf1 JR uriuT subjtrl>;. inrfudiing fhoaC t'hR..~ punutY lxtcc cariuuY 6+rms uf thu+c tlieunlerl• (TaWc IN 1. 1ltc dilTavvncu WaN sit;nilGr.nq :rt thc 2.5 pcr trul Iv.1L . . r.VUI[.\L t'INU].\NY I/N.\Nf In..Y.LL! \L.~YI\/:fl\I./1• 1•1114\T.nl ~N'Y}TI~NIIKK. .t11~1\S . /IN~. ITr: . Iw\. Y{V. .U.o.m..L..n fd . T1.M1 . 114 ' !Ut.f -------- ~ !.?./ n.fo> V>o.n3 ._ Texl.e. 1\• ~ mNN..r.u.wlsnwr . . - . . .mm ~\Nn]19 YNYN rN,.u' MN PN M1TI T\Y.RT. tPml 11NY11?/t16\NITY)IYRMRFrM~s.\1IM1 1•..IITIYY..~jl'Y1rM1•~AhLF.nN IW iTl'bRSTf . Onrti.INS bll6.LSM. . r\N8uN5 ulerouv , . CXR - ; . ufM. . rSr. ' 1kxNk.r tirwk.r. " ' 140 ~ 7 ' I8S 173,.1 --_-_ •~ \.T- 3.17 QOdS>P>o.ulo . . /)f the iwGciJual Le•tnro audia.L mle of the rnrnr si>;ni8c:tnr d~ff.rcnroY . lwlw'ual Ymnkcrn aud unuYtnakcn \r,ls fnund in reslNSt tn thl: x•rtun chuksteml Ie,dL This Clct iY a ncw tindiug, uf a.meiQenlblr pnurfi:d init•rt•.r• 1 13 T•Iblc \. r'Ir Ycc that :It the Ihrtn lu\I•cr cholc.tl.•ml Icvdx (unrlar !511 mg. Ixr 1tA c.c.1. Ylnukl:rs arc iu the minurip•, ahcrr.ls :tt higher IL•vcb (of ->Sq mt;. pcr ceut nr ~ 00::0615
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I 'Ihn t)•,r ;••.I i! hr. S. , td•.o r'. F. . r . palltntn~74, \r+r r- ] ork• \.I', STATEfIE!:T OF DS. S1iLLD0F C. S0:15:EkS, PAT$OLOGISi. • YEN YOCS, ti.Y. '1'hr t.lr.auor.u. N-elrome to tbc cnnmtit fcr, Dr. Soamners- You nray ptnmc•d aF y-mr see fil. lit. Snnu:us. 'Ilmnk a-nu, Mr. Chairman. I nm appearin~g at the requesl of represent:rtivrs of tlre tobacco itrdusfry. ]fc nnmo Is $heldon C. Sronmers I mn a physiciatt specinlizine, in pntholorv and director of labnrutories, Icnnnx Iiill Ilnspitnt. ~tien~ Tnrk, \.'1.; clinical professor of pnthloo ytColumbia Univelsity Col- kqto of Physicinrs and Surl;mns, r~'e>c 1 orrr, aml ctinirni prnfcss>r of pnlhologp, University of Soutlrern Cnlifornix Sdmol of Medicine. Lw Angeles. I also tcaclr nt Cornell ltledieal School, Tnfls-Now Eq>•Innd Medical (kot.er, and New Xork Medical College. I arn n{reterans' Ad- ministration hospital consultant in pathology. I am the editor of Pntlmingy Annnol, a renrly EClmkrl•l,y lnthlicntion compoaxl nf e'.inys I writtcu br nnd for pnlholnpists; I srrre en tbo editoriol Izarrds nf 1 no jonrnals haro nbmd 2?0 medical publications, and nrn tlm coauthor of I a gyrrecwloD•y texttxmk. My curriculum vitae and publications nro attached. For 2% A enn I hore been on the Scientilic Advisory I3oar'd, Council , for Tobaceo Rescarch, and mn currently servinF on its snbemnmittee ~, to rrrrnhlate rrsr.arclr proFrnms nnd plnnninq ro the ficld of tobacco C and hrnlth. Rcecntly I Imve been appointed rusenrclt dircctor of the C Council of Tobnlwo heseareh, as part of a newly initintcd prot;ram ! 23 to broaden Ihe sco1ie and slrarpen the obje.eLires of Ure supported ro- C senrch.'I'he fnnds budset.od for these parpuses have been considcnbly ~ Ln aucurcuted. ~ ,~ Attlri.• pniu41 fu Chnirmnn,ynay I present for tln, recnrd stntcnreutv b D v c Cfareuw Cook LRtle, ~rho is tle selentrfrc drrectoq nnd Dr. I_(olm_ rt C. llnckett, the assoemte scientilie director, of tAte Cotmcil caroh t TI>n orr.,m.r..x. Witlront o octton, oy nr tnc u m or•d follolvinF ymlr testimony. Dr. Snarirnte. Consideration hn been given extensivelv in the cm•- rent Irenrltlgn lo tlre lptcsliou of smoking anrl hralth. Ilmre=t n-ialo diRerences of opiniorr as to tlle importanr•e of relwrerd stntislicnl ns- •or•intiong betare.n cigarette smnlrmti arrd vnrinns diarnuw ain held by liresently active vorhet9 in the pertinent 6r.lds of inerlicnl science. It wonkl he uninir to druy the exi.qtence of evGkncc both fnvnring end opposinlr t.ho belief tJrat cigarettes may be or are asso;inted sln- tisticnllp with varions human diseases. Each individual srorlring in this field is nntnrnlly in0ucuced Mhis particular scientific discipline, experience, and the results of his own experimcn,nl projects. I nnr a physician particularly interrsted in lnunan discases, their consee, the staFes of their development. and the cnnscr~ucnt opportunities and strategies for their control and pre- centlou. DlnFnosis of aisense, paticnt care, and disease prevention are 1;:;;.,., r:mi rr bas arou.-e.1 ILr er•-alrq puhlL: ah•I C')1frlJr.r,ltal ill Irn.l. L-Irc mrrt rnmrmm lvlns nlfcrl Inal+.= fnt' nr >I. Umra o,•rt nfr..:1 tlc•n (rc,rdc=. \o ll,rurc of rnus:dinn l:un..u I>ns mh"q•mtet e.)d?iued thisslrilcing sex tlilfrrence. +4 omrn, .clrrlhcr r6ny smolce or not) nrc le , eus+cpl ihlo. It i~ 4nul• fuI rhal notable I)enelitr.nnlll lm anticll>ale+l in prec¢nlin" lunp, co>u nnron^ Womcn hv nu~~ Inoscnt puhlic hcaltI> ptngram. -1monE men, rvho ure relnticely more likely to drrelop lun- ennee only a srmdl number of nren heavy ci„alitle smnkcrs nre found ha~-c cmrccr. "Fhis nssociation dncs not cotislit tile c'msation. OI thc lut )wpvlation nwst kcacily ccprxsed unly a snnll minoril.y suhprot is affected, anll why is unlrunicn- Lmtq tanccr does not occur in tl preat. nmjority of eit.her moderate or Ireary smolcerx. S:nlistical cot pnrraons l>et,areeu smnkcrs nnd ueusmnkrrs mr di Rcult to wnl:c ai Ilm mlroducinp two scrious types of scimriilic bins: (1) 1>cople s:lf-sclc nlwther to smolae or not, nml tiw populations stnchcd lhus uro n rnndnm: (2) no mnthetnatics exists for 5tntistical cOlnpal'150I13 •nunrandotn' or sclected pnpulntions. Medically trnincd pntLolo•,Iuts would not emplny dcnlh cet4ificn . diarnnses, unconfirmerl by a slody of tissnes grosslv nnd microacoy cntly nt surRerr nr nntopsy, in snclr inccslipnlions.'f'hc ovcrnll autoll! rale in thr. United Stntcs is below 10 percent, mrd without suptwrhr datn there are too many death certificnto errors in distinRutshir betAeen primary Im>a cnncer and secondary sprend to the Inng r other cnru:crs, nmong n number of dilBculties in the scientific use r death certificates• (.nnp cancer is of sarious typcs, and severol have no inrfAied rel:. l ti ~ i f r on ien mp l.ionslnp to any envirmmllentai ngeut.It is a firosa overs lump together nt. lenst nine different tumor types nnd nscrrbe tiem a to anr ngent, including ciRarettc5. l rl`ter at least SO ycnr5 of r.~pcrimeutnl v:orlc, and many smo inhalntion experiments iu animnls, lun~ canr,acK nf the mosl commmo rqmunons cell huumn typo hnve nnt been prodnccd. It is usunllr •liffi<:u to 1lrnro a nep,nl ive, bnt if ciqnrrl fc srnnke +rns n cnnso o f hmF canccr, is thdecll sm.prisinF thnt nn nuimnl csperintent5 hare srlxectle4 in i tore stud). is m'Yrntlv ncaled of Arlmt other faclors, Eurlr ns rrrn5r- url.:m air inlhrlaots nnd dr~enrndivo chauM cnMrihnte to luo cancer devnlopmmit in nnimnls nnd mmr. \fedicnl fashions change; for esnmple, RO yenct ngn nnQmritics cor sidercd tuhcrculosis llm mo!A, r,nunuon cause of hu>f; cnnrr.r. tt is alr evcll to mootion that tu+tlcrttanrliu~. the fmmation of loup; cnnccrs mre of tho most. compleX nnd di0ir.ult prnlrlenrs iu uu,cer resenrch, m prrr~utJy ,rcll nnderelnod nnd not ciel,amg simplo an .accrs. A rccnud even Inoro ecrinus mcdical '>roblan is cnnllorascolnr dl eaec,sinru it cnusesaLmlt half thc total Ilcaths in tlw Unilerl Statcs au orernll nifeGs InuFecity. Innre lhan lnn~g cancer. Agniu, it ntencl mid,lle-aqed ornlen more oftrn tluu, femnleq for onl:noirn rcnsnn In tes'rect to 6tmkinfr ns a pnssible cnuse or contrih,dinp factnr, nen-r multifnctnrial statistical al.ndirs I+Izo pnint to a fnmilv bislory nf heai hisease, diet, blood clmlosterol, bnde lrelqht and hlnwl presvnro I
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-3- The findings are not secret All the above reports have been published in medical and sci ntific journals in the United States and other parts of e world. The e documents are available to scientists and doctors int ested in pursuing the scientific truths on the smo ing and health issue. The work should cLo forward Theare eminent scientists who believe that the question of king and health is an open one and that research in thi area must go forward. Frcm the beginning, the tobacco industry has believed that thelAmerioan people deserve objective, scientific answers. Wit rea 54 qQu this same credo in mind, the tobacco industry stands. y today to make new commitments for additional valid tific research that offers to shed light on the stion of sasoking and health. The Tobacco Institute ,7u1y, 1974 7" 0020636 TIFL 0305623
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,,~..- \unw.i AsPHt'Tw uY roNrl%ANY UIKP_\66 A?U INr4;8TF:N+InN 201 Wc have reputcd the precnlmtee uf hytu•rteusiun uud cun,unry dixax. LotIl setztratelr and cnntbintd. iu twu surressivc l;tvter.ttiuns.• ln this Iwrtiou of th, studa•, the grandparums of the stutlents u•cce eulled the purrnrul ,trnerutian while the studutttu fxlrunts. xunes• and mteles comprising the sc:coud geuer,uion \cere called the offepring. Three typef of parontai matings were cmoshlvrnl: Type I where both marital parTnets were uRccted, T}'pe 11 where one partuer was:uf\cmd, and Type I I I where nuither Iztrnutr,vas;iRceteKlr lit every case, thc prnportinu of affected utfspring was I;reateate where both purents sutFerutl from some form of these disortlen an8 laut where nvither parent was aRected. Lt the c,vc of the combined disorders. for c.xample. the intidences of disease in the offspring of the . three typas of mating were as fullowt: Type 1, ?2 per cent: T)'Pe f f, 12 per cent; and Type f I I, M per antt. Thus, Zi times as many offspring of Tppe I matinFs were afft.•cted as offspring of Type I f1 emttings? The gr.tdution in disordermtus among thyoRsprinK of the three types of mating is consistent with the \Itudcli;w law of seHregation. More evidett\e is ntaltYl, huwc~er, before the gntetic basis for these disordcrs is full.• establishal. The vttrious pnttcnts of purerttnl discose pro.-ide u basis for ckls.ifyiul; suh- jects so that the frequencv of a trait among studettts n-ith adverx.iuherit:mce . and among those with nonnul purcnts nutY be comfztred. For e.vmplc, a studp was made of the diRerenco to be found between the oRspring of hypvrtensLr parents mtd of normal parents in regard to a number of characteristics relat\YI to blood prttwure• heart r.ue, circulatory h,rperrtttctivity, and overweight.' In ttener.tl, highsr, more labile blood prasurc mtd heart rate ans{ eveneeight werc more (reyucttt among students with a positive parental history of hypertmmion_ ilthuugh thddilierettce between the turo groups as to incidence of single tnuts was often not great, about 40 per cent of the offspring of hvlXrt\Y151ve parcnts had muf7ip/e ptxitive traits, two and a haif times as many as were fouud amnnz the offspring of nvrm:A parents. 5[uttcnts with ktyp¢ttensive parents were also more reactive to cit;.vetre amokivg than were subjects with normal p:lrents. while thosu with coronary parents were less reactive The efftct of sntoking x singfe cigarette on s.ytoiic prescun, diastolic preesure, pulse pnxure, heart r.tte.- strot:e a•olume, and card'cte output was measurtd un n table bullistocardiograph.t The peeeentage incrdtse or detrettse from the control vnfue proalund by smokinlt was determinett for Kroups of snbjects which differ as to inheritance. The ofT- .prinx of hyperrvtsivc parents were characterized by an extiti:erated lnen.'Jse in cardinc output amountin4 to 992 c.r. per minute. or 13 per cent above control ralues. They ulw had the grr.ttest average rise of systolic and diastolic prersure and he.vt rote, and atroke volume did not decrtasr. On the other hand, those with coronary parerts were chararteriztd b.• the mnst marked diminution in stroke volume of anv Kroup, so that the inerease in tmnliac output after smnkint: was much less-only 117 cc, per minute. or 2 per eent; compared with 399 c.c. (S per cent) (or subjeets with namul parentt Thtse diEEcttnces vtre statistically siKttifitant and strongly su•s1~eat that thv circulatory response to smoking in healthy young adults depends ilt part upon the physiologic heritage of the in- dividuzl. Turning to the coroturv end of the spectrum• we have found that hcper- eholestercmfa, or cholesterol [evels of 300 my. per tC0 e.c. or more amt at l=st one 1 I T' oozo611 TIFL 0305585
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think this is gain to be our only rr New York Medical College in New coursu e•ith this isease. With surgery York City, whu has built a sttong case and radiothemp _ we am not saving against cigareties witls his smoking 5rm of the 63, 0 cases that occur beagle studies. About a year ago, Dr. , annually:' Saccomanno began a study with 300 i Dr. 5accoman o now feels hc has men who hud cither stoppad smoking. ~, histologie proof o healing to back up mining, or both, and 50 controls. AI- fhe statistical da of Dr. Oswr Aueo- ready, the sputum samples from some f backt the patholo ist at tho- VA Has- of these men show improvement. In pital in F~st Ora ge, NJ., and at [he checkiny baok, it turned out that for March toward m cells shad into sp pathologist sees But carcinoma in lignaney in three autopsy specimens was retlected in rturrt. At regular and irregular metaplasia, iape for complete reversal if smoker stopsL situ is probably a point of,no return. ~ v 3N J}~w~ -. ; ~l'. z ~} . ,.. Je(E q.. ..Yi~.~ _ ,.. most theioxia inhalant had been re- moved about three ycarx before. sug- gesting the time required for healingto become evident W henever Dr. Succomanno does an autopsy on a victim of lung eaneer, , miner ot not, he sends the lungs to Dr. ; Auerbach, who makes two sets of ;." slides of serial seaions of all the bron- clii,bronchioles, and trachea. Dr. Auerbach keeps and studies one set, the other goes to Dr. Saccomanno. Then both pathologists examine thcse . secdons and determine the gradual •changes in the lung. °We actually see areas of perfealy normal epithelium, araas where the epithelium shows basal xtl hyperplasia:' explains Dr. Sacco- mmmo. "We can find areu that show svdiation effea, carcinoma in situ, and invasive cancer." These areas ate mapped out on a schematic tree that . was devised by the N ew Iersey pathol- ogist This intensive e:amination has yielded some interesting findings. In 1965, Dr. Saceomanno diagnosed lun., . cancer in a patient on the basis of his , sputum sample, but x-rays could cot locate a lesion'. Two years later, the . patient suddenly developed a tumor -that was visible on x-ray. This malig- naacy wos rapidly fatal and at autopsy, D r. Saccomanno found an olattlf can- eef, a highly malignant type. And he . found another leaion-a carcinomn in ' . situ that he suspeeb produced the ini- .. . tial atypical cells two yeats before- Another patientt a, woman, was t'irst diagnosed as having tumor eells - in L962,but x-rays were negative. It was October 1969 before the tumor became evident.radiographically, Dr. Saa«nanno suspects that the tumor lay quiesant during the intervening - ~ nearly eight years, in a sort of balanee. . - betweee the patient and the turncr.: For this panialar patient, Dr. Saao-- manno is quite opdmistie The lobe ~ has been removed, and she has quit smoking. "I think her chances ans . gotict.., But he prefers catching the growth before the point of no return at carcf- noma in situ. As for now making it pcssibte to acert a nrslisnanvy thnt may be ten years away, the muJest man of the mountains quicoy says: "What nicer thing cuuW one do for .hummtity?" • ro
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2t10 nn 2. Bcfurc graduntiug frum un.lirul n•ha>I, nsarlr % pur ccut n( thc studcots h:ul lost nnc I;arcut fmm lhesc diae;unt, inrluding xudden dcath. . 3. Atmtht:r 7 per ceut have a parettt living with severe disease, uy indietted by a history of coronary uecluwion, stroke, or cartliureuJ fnilun•. 4: Eleven per cent of the students have a parent living with malente or mild diseusc. int'ludiny;mgina pectoris antl the less severc fornq of h}pcrtensian. S. lu udditiat to thtrsu with positive pa reutnl hixory, approumatcly10 per cmtt of subjecta have a p;trettt with questionable hppa.rteusiou or corou;uy disatse. while a similar numher have an obese ar diabetic parent. - - 6. A fexsubjects cannot deterntine their parmtal histon. acrur.ttely br cattse of divorco, eurl}-death from othercauses, and sn on. T. No more thau half•of the students in medical school c:ut de5tdtely state that both pamtts are thus far free from these four closcly related disorden. l TAnLB It. 37 FAT.LL C.tet:S nf IlYt'eeTtlsnl< AXn/Un ClN1U.'AYY t/1lYAik :\IN\1l: h\el:ITS /W 724 Jnn.ve H(wae,s \tt;acAL Sn'utnta I Alie AT 91:ASM T[M]II~AL rAMR qT CILY9[TW~ . AIr4CiL0 S' I ~ 39 0 I i 39 59 10 30 I 60-09 7 :9 ~ . ) - 3 ~ ~ - - ~ 0- Cmumry O.rltuwn Fathm ~ 34 - 2 7 ~ 16 j 8 ~ 1 . }tochty. J 2. 0 . 0. t I 0 5tr9[te Fathers ~ 8 0 1 I 3 I 2 Aiothen 3 0 0 $ 0 0 CGtdioreeal Fattune Futhen 3 0 3 1 1 0 >tuther. ~ 2 0 1 1 o i 0 Futhen ` 47 I 2 I 1t 19 I 1 2 ~ 3 I \laehen I 10 1 D ~ t 6 l ; 0 Total . . I P2rtnts ~ 37 i ; i 11 i 2.5 ~ ' 13 I 3 Analyrois of the 57 parental deaths shows that coronary oarlusion, Inclucfing sudden denth, accounted for about ttvo-rhirtls of the fatalities (Table 11). Stroke ' crused nearly one quarter, while tardix or renal failure accounted for the re- tttaindea \eaAp Hve times as many fathers died :>i mothers. Thirteen of the 34 fathea who died of rnronary occlusion had had one or more prerious attacks: half of those who dietl a coronary death in their 50's had had their first heart -. nttaclsintheir30's.-Votonlydidthemaleslier predominateinregart{totnronan• deaths, but more fxthcn died from stmSte as vell. Before the age of 60, 32 of - the 714 (athen and 9 of the 724 mothers had died from etrdiovascular disease of ~theso types, an incidenoe of 44.2 pee 1,000 and 12.4 per 1,000. tenpeetively. These mortality-rntes are by no matns final ones, since the majority of parents were considerably undcr 60 when the data were obtained. If. in the coming yean, the prevnlenve of ch.x disorden remains the szme, well over 5 per cenr of male meditnl students may be espected to die of cnronary dise:ue or snme farm of hcpcrtensi0n when in their 10'3 or 30's- .
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1 Z 1047 E I Organ des Berufsverbandes Deutscher Internisten m 0 a Jahrgang 14. Heft 5• Mal 1973 der Umweltgetahrdun a- ~- ^ ' Internistische AspekteJI! -j Redaktion dieses Heftes: W. Ruge, ann~er; F. Valentin, Miinohen W. Rugs, F. Valentin: EintUhrung zum Thema 189 G. Lange, G. Klein, M. Zimmer: Gefifhrdung der Gesundheit durch Abgase 191 H. Liabmann, K. Seherb, N.•H. Relchenbach•Klinke, B. Wachs, M. J. Forstner: GefBhrdung der Gesundheit durch Abwisser 196 A. Stier: Zur Bedeutung der Biotransformation von Fremd- stolfen: Primilre Giftwirkung durch kovalents Bindung 202 L. Loeffler: Umwelteinliusse, die das Erbgut verandem oderveriindern ktSnnen 212 E. Wende, J. Kiitter: Menach und Umwelti8nn 224 G: Terplan: Umweltbedingte Rudcst9nde in Mileh und Milch- produkten und ihr Risiko tUr dle menschliehe Gesundheit 230 H. Schievelbein: Zur Frage dea Einfkissesvon Tabakrauch auf die Morbidtt9l von Nichtrauchern 236 Buchbespreohungen 244 Tagesgesahtohte III Indexed in Current Contents Springer-Verlag Berlin • Heidelberg • New York TIFL 0305612
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Imandin4.qu.. l.,ii! s unt n ruua~. A nundxyr of studics shmv nnrclntimt of sn~olciu;; Iu Lnarl Jiscasu nnd nu;;Ll not lro i~norecl. Aging nnd cucniu,ry urlcriuvam•usiv, of rums,, nvors;lnulou• uthcr proccsv-5 ttud c,ma-i Lcun Io LLc mu~tcnimnon typu n f Lau'Ldisensv. AnotLor dilllcully tvitl, u.rnuxry henrl. tlisensu couecrns how nreo- uHt•Iy thc Ai;.,mnvis is mnJn 1VLat 1116 mo.st xdvuncrd clinical tests nrc.umploy,d, ovidum:o for .•nruu,uy disensc is famtd in nLmost Lnlf uf nll mou ~.ror -lu yc+us. IlY this ngo lirnctimdly nll the cormcrty ,u'tcrics shu+v somc pnlLalugic lesions. Sinco both eoronnty dia:nso nnd cigerette smol:in.• tuo sd common in the U.S. mnle poltnlntion, it is qmte dillicult to Ilnd aduqunte numbers of pcoplo for compm•ison who have nuitA+cr, or only onu of these couditiuns. A well-known shdis- s of auch unequal siu; nro emnparod. - - - - Emphysanm hns now been added to the list of disensea blamed on ciaittottosmolciug.'Phu newest medical pnblicntions nnd governmental vcpurts emplmsize Imw dillictOt nro the diagnosis, tho clussificatiott, nnd lhc giudiug of suvariLy of pnhnonary etnphysnno, evut mnong ov tcrts. 'fhu cnuu: ndmilledly is unktrown. One common form dn- vo~ops in cret•Y put•sml with age, mtd lnmping sevornl types as if they comprised nu entity is unworrnntod.'Plnts death certificnto dingnoses or n tnutino tmlholo••ic clingnosis ot emp~,ysomn nt pmsont aro sri- entificnlly 1nor.ticidly a;.eless oxceet in a fotv specialized research contets. ln Ihe curreut era of t•elattve ignornnce concerning ho.r to delittu nnd Wcn,nizo emphyscmn nnd ollwr clu-onie tung dise••tscs, no swrepin~ q+~uundirntim+s us to cnusntion cnn be justifictl. ]n t•uvieu•im• nbovo a few selected disca.~pancies, difficultios, short- comini,ro, nnd imsulved problems in the field of imoking nnd health, there ts no u•i41t to doniotrtu tLe eoncanlavtcd ettor/s tlmdo by mnny wm•kere to liutl unswerv. It is simply tlutt tlw fickl is too now, the fechuitla4w still Leing developed, antl the conclnsive proofs not yet iu. It is Ic.,; tbnu 90 yonrs since hotg surgery bermy for esmn~~~la A ferv ilcros iu tlto testimony of others mny tnsnfy wmmont.'1'hs . ' Surgoou Qenernl cmnpmnal inubility to demonstrnto the formatiotr ~of lung eaucets in erIu:rimental anioluls eaposul to smoko witb hick ~of expor3nteulnl protluctiott of leprosy. Itowever, leprosy hns.been prodnud in nnimals. . Somu confnsion. uroso througlh use of the word uoddictimP' in con- nection with toLacco nse. tty, ut (,ernll accepted WHO critcrin, smok- in~,•~ toLscco is not considctcA nn uddxction. , Urk Williams of thu Anrerican Cancm•-Socicty stated that nt>hysi- - einn looki» g nt n slide of Iwtg cimcor without mfm~mation cauhl tell in sumo detail ubout.tho poUent's social life, ciem•otto smoking for sontu "0 ycm•s, tmd so forth. On tho basis of my dnily oxpcrieutu as. a putholot;ist, whmt one lonlcs nt u slidu of lung cancer neither a ~ patlmlc"ist nor othor f,hysicitms cnn tell vrhetLor it Is from a ntmr or wonnin, aod tltos cunnot nccntKlely describe tho social life. hor- ther, it is oot passiblo Srnssly or mfcrosco~ticnlly, or in mty other lnty knowu to wu, to dtslingotsh lmttyfco tlto hmg of a amoltet• or it nousloolccr, lllncl:uning Ql htu69 is Yrnm carbon particles, and slltok- ~ iP8 tobilcco doc; tlot intrahtcc inrbml pnrticles uttQ tho hnt~..'lYlu I cducnt.ionol vnluo of ll+o vtuious stttoimcns sbotvn the comtni~tce in ILis siltllttimi csrupes mc. , I . . . , • As to coron:u•Y Leett discasc, n spokeatnnn qunted LLe dnnn of ]1nnaL Sinni hfetlit..-tl SchoulYn thn e11CCt thet the relntiory of cignatvUee smek- ing is ns linnly u;•ltrLlished t4s Ufo lltcr+pmdir. uso nf nnticnu(.ndxnl:: fnr treating ntyocmvlinl infnretiuu. A rc:out ttblicutiou fl'nm l'nlo Eledi- cnl School amtlyv.e-v titc usu nf tutticcxa•n1'nuts nnd conclmlrs that ll+o studics m'n twt wcll enough du-ligtuat lu draw aty nw:ftd ctmclu.r-imts. 'f7tesu arn cited as ovet:Anlemcula or ntiaslntumuttv uf inedicni knowl- ed•m mndu by sotnu trilucssrv. T'Lo ff;/-Letrr.pyrcuu is nut proved to Lc restwusilde fur humnn Iung cnncur, mtd eonseynen9y its maouut m• tl.n ronwvnl of it ezut sanrccly he considered at present crucia l snieuli Qe mnUcrs. b y Cigarott.u smolcing is unt a uuiqtw health lmtnrd, ns clnimed Chnirman ffvde of I?CC. As llr. ICatin pointul ortt, no myst ical prop- orties me M r u ' otcttt h.s oot bcmr proved to be a LeolUt hnzard at nll. Many figures wuro cited eoncernin{; 90,000 or 60,000, ar'200,000 per- sans per yenr huving or dyintt frola Itltl° enlleer ol• tlle nther (lttirn9e9 bcingconsukt•ed..${nco tt ts nct known u"hat tlto cnutscs uf lung cancer, eoruunry henrt disbnso, or bronchopnhnonury dlsensro are,llto nudlipli- entitat of uwnhers does twt amtrtLuto to undetsttutdiag tltrm mtybettot•. Ouo recent article oit the millions of porsons reported to httve otia of a lonA list of disnnses c•nncludes thnA, lhere nntst bo scm•ccly any hoalthy peoplo left. . Now to review brin0y tlte spcoifie u•eas of deficiont knmeledgo :md ll+e resean,h nexlect for bettcr undcretandity; of tlte major discuses c6timtsl tn Lu assuciated with citi rretto snokin{s. As eancents lung eancor, uudtifnetorinl st+J.istical tcchniqnes nt•e noe in usu opidemtologically, and t.1u+y tnnp lw expected to provido qumditutive esttmates of tho tclntivo stntistlcal iumwttancu of urbnn tmtideuco, nceapation, luug infet:tiou, uud Inherited tuudencies mnong other pns.viblo factors, ineluding eil,ntrettes. \Vo strive for a better ngreetrtetd tnt the eWsstficntion. of so-htlled prouncorous lung contli-- ttnas and cancers nnd this is slowly being achieved, pmtly by Inter- rurtional aoperntion throu lt 1Y$O. Teehniqnes to study virnst•s, in-n cluding chronic virus inffi.r.tions aro now becoming moro tvidety applicublr. 'f'ho preduminnoca of maleg n•itlt lung cnncer mtd the evtdeneo tltnt mon who knvo itntg enne¢r• nrn endncrinologiattly hb- notnmtl ldqn deserves mm•e study. . Tn nninral experimonts, a sttitabluhntg bionsstly model for lnhnlntionstudies is earnestly stntl,dtt and tcelntical advances rnny be nchiernl within /he nc>t year, Notv tccMtiqnes of histologic, histochcrmctd and biochemical stndy noed wider appliantion, mtd pothola•ists rrill need help to npPly 17tese speoisl matltitds n)ore widely Lotlt to iuunan and mtimnl ntatennl. Exposttres to buth tho gns phnso nnd lurrticulate phnso of cigatette smoke nntst be designed so tlint tlte chemical rcoe- tions at parttctdnr sites in the lnu},c nray be nnderstnod. lloses nud ro- ]atcr) responses must bo evahtataT. Although hitherto not fonod, an mdmal model system for pruducing lung cancers lil:e the comnmon hn- tnmt tylxs still nceds to Iw aoul;ht. ; Tn rrofetenco to cnt<liove'nmlar di"tnses, ndditiomA nmit.ihutorinl stntistical nnnlysos nnd pntholnr ic stuclics nre needed.ll'o will andem'nr to determine uceurntcly whet6cr artcrlnsctcrosis of tl+o enrotnu•y at•. tories und anrto diA'ots in its derclotnnent or <ncnlity nr in Qu:u+tity
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2L [.w4 P. S., Slvelt0._ Ciuiul studies, Suppl. yioe C'e. 197i. p. IIrson, P. S.- Silvette, 3p, UvAhR. P. 1, Can 135 (1970} 31. LuWette. A.7., 10, 533 (1970). 32. McFv]au4 R. A.: P. MOtW9., P„ O'Donne N.Y. Aad. Sci. 174, 34, , teuc.t4 O.: Tabalva und Filrntion. In: H. H. Sc11(Nelbein: EidluO von Tabeknuuh auf die Morbiditit von Niebtnucbpn : in 26, S. 434. B. L: Ann. N.Y. Aqd. Sd. 174, C. W., Ma'd, D. ].: I. SrA. HBh N.Y. Aead. SeJ. 174, 301 (1970). , R., Heio{i, P, Theodose, L: Am. (19ID). rA - BAdunp, Zuslntmemetzun¢ bein, Nlkotln - Phwukn• loiie des Taba S. 5. Slungart: Ihicsw 1968. 35. Ra9, A. M., Rock.all, T. H.: Aan. N.Y. AcW. Sd. 174, 243 39. Syeer, F.: Arch. eovrtonm. Hlth 36, 443 (1W~ 40. Sr<h, M.: Dlteh. Z. ges Eerlcht. Me,t 60, &0 (1967). 41. StewasD R, D., Petasoo, 1. E, luetn, E. D., Bachmd, R. T, Hosku, M.1., Henmem, A. A.: Arch. emiroom. Hlth 21.154 (1970). 42. U.S. Public Hea1W Servioe. Air Qualit9 Odteria for Carboa Moooxide. Waahiytou, U.S. Dop. of Health, Educatioq and WeRVe, Public Health Servia, Nat. Air FclWtion C.entrol AdodniMtiao Pubikation No. APE; 1970. 43. WwquP, ]., KycMSeo, K, Astruy, P.: Atta path. mkro• biol. ssmd. 75. 353 (1969). 44. Wilbert, L,: Med. KIln.66,1190 (1971). 45. Zovmen, B. M.: Ann. Alkr® 23, 371 (1970). Prof. Dr. IL Schlevelhdn 36. Savel, H,: Arch. mv'u . Hlth 21,146 (1970). Inst. f. Kliniscbe O,qole uud 17. Sehulte. 3. H.: A[dl. ,¢omn. Hlth 7, 524 (1%3). Klinivche Biacbevde der UnivenitCt 38. Smuklnt and Healtb. Pot of the Advlimy CUIDminet to Abt. f. PHvennvmedlzin the Surt•on Gemnl tbe Public Hralth Servits. Public D•B000 Munchen 2, Noqbsumttr. 20 Health ServAe Publiat an No.1103. Wohm{ton 1964,p.49. BundesrcPuhGk Deut4chiend a 4 TIFL 0305620
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the n aidng controls. No relationship of this increased prava- lence ould be demonstrated to alpha,antitrypain deficiency (see below . In addition, nonsmoking relatives and smoking controls were bserved to show appro.cimately the same prevalence of ab- norm itiea. &owever, due to the large proportion of females in the nons king relative group and to the clustering of two-thirds of the ected relatives in 10 families, fu2n conclusions cannot at presen be drawn from this study concerning the relative contriba- tions smoking and of heredity to the pathogenesis of COPD. In o der to determine the relative significance of smoking and heredi in the pathogenesis of COPD, Cederlof, et a1. (.;5, :B) have used t e twin-study methodron registries in both Sweden and the USA. e specific details of'this method are described in the sac- tion a Coronary Heart Disease. As may be noted from a summary of the work at the end of table A2, the authors compared the sympt m prevalence among monozygotic and di2ygotic twins who were oth discordant and concordant for smoking habits. They observ that the hypermorbidity for COPD symptoms related to smo ' gpersistedevenaftercontrollingforzygosityandconciuded that a usal relationship of smoking and COPD symptoms was sap- po However, genetic factors were still found to have an appre- ciable nence. Lundmann (159) haa applied this method to the study f pulmonary function. Ha studied 37 monozygotic and 62 dizygo c twin pairs, measuring forced expiratory volumes and nitrog n waehout gradients, and matched the various pairs for sme ' g discordancy. He observed that both of these parameters were versely affected in twins who smoked and that these changes were rreiated with cigarette consumption.'Che results are out- lined a the end of table AS. - A(p "~('A;A1')--Of'nwrrrecent.notrand-disem-~--• sion beew tfsediseovery of an assoeiation.between aa hereditary predis ition:to..COPDand the relative-or- absolute-abseoce' of' alphs.trypain;..a.asntm glycoprotein enryme. Eriksson (78) was first Investigator to observe a relationship between the pra of markedly deereased serum trypsin inhibitory capacity and p obnlar empbysema. Since Eriloson's paper, much added researc bas been published concerning many facets of this intrign- ing It a that A,AT defidency is Inherited as an autaaomal recros' e trait (78, SIe) although Kueppen (t:3) considers the trans sion to be by an autosontal ecdomtnant allde. It haa been eatima that up to 5 percent of the general population may be hetero g6us for this gene (155) although full crosrsectional studies of the population remain to be done. Hom rygous or seven deficiency of this enzyme has been asso• Too2os23 3k 1' ciated with a part(• majority of Iungs centrilobular defo: hereditary disordee lower lobes (1o1, found to have the include a greater p served in the senee earlier, is more se tough, and frequer bronchitis (101, 21 patients have reve: and increased vxsc estimated that betr this homosygous dc found that almoat : by the age of 40 ani in pulmonary func sons with homozyg uals, 4 smoked nni of the two asymptt vital capacity. Au and to have decrea: - It has been su- hibitor in the serc emphysema in the blood contain simti . the overall defense these cells during : monary tissues an itor, may contribq- lung tissue. Heterozygous ir levels of A,AT in' with homoxygous debate about whe greater risk of de.diEtenlty is the la present, the best n appears to be thc cause levels of try to rise acutely wit Welch, et aL (- creased. sasceptib studied showed a:
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fit.\:6\fTL'R:B:iCn :.r : ~aoxsrs ;.ro n'os:atr,t;zP~ '.+51 1 te: s c•. dccnoinr w•Eta~:.trt or n i; r-.,linr._: f^r.nts taty be .v:^.. dr;cvr. . iaderllii)-:eu,t••.! I:i t9t•tP nI t!IL• :>utt3 of . ~ lLe pn-.rut +I cdy. suris r.n L=,_ a. ,. :,-,>a!d apprar pr•,uta6!i•0 6 eIY:M)n 1QCB'prn %r•r:LtOna: (r.::,:f. .tat Ct~~rcttr f:nr•r;,~. er. la•Clr- dH uf tne t-pXtC:WC:o_o .. :.t.;; rl:aeer. r:nt, t6r k,•]r rspluna:ion af 6,1- r:+E.r+r,: L•roriati0n i:r;v:a,•:t r.~atrtr.• s:::okinp rd in t!:a pr,-srnt >ta,ly, cb;,•; :. t tn 6., sulGocmtk !:i,b cn 6p lune.cmrrr. To oLtcir. n! t::r of n.~in:ion hr- twrn r•motinnal nspunsr and tn- er.lakir.~:, a'c tl:nu;;i:l it s,.u i i,e of nreaL 10 run,lAttt• t!:P ri:k u. !~ti•.qtr .n:•,wing for y`'ftrnNlii~• res nee relit9rr tu thnt of arr!ry:,uac• n~it!t a ntr(!lod . Slt h'itn! IIV C+Urialrtlt U0). t!.r rn.pntwvs ,c,•n• riQ,.•r in :r ••r : not bu:JUUmorl ore thr•I,a,i.,:,';i,i• prt-rut .lata. 1 rr t'eGnl+f.:uetlmdd mi+;L•t the oi tiitfr:vnrr. hut ti::+ rrtto s:nokrn ns ,~oatpar•rl lo r.( nun•nl.,i;cr. L7fi. .Li:,piu,d!y. ou tnctiwd of mre.+urintc r:no:io::,:L asnn:.• v rntt:rr or:nlr• m:d !n-ril,p+ cic n to arrottnt fnr thr tenfnid nl tuort:tlitr for ri.x- cris: oLtainetl a-ari ?.. Ol:cin::_Ir !his d,}zr•- •.r iatinu ia r.at r.untue nnd the noytflQrr :ra,, "tmat:etirnti.;' •I'ilr hi_lu•st n•L•tti.-n t4snluptinn Iliat :hv.iu'nl:ul3: "anur,iiic'O ra;r;Y•ri,x Worp h"nol:TUti<••• n'. 6lntlrr °no4nPUMtN:'• . tiiL:lih:[ rPt::pn:alinn- acvrr thrn nMtle Un,l,•r th t tln• mt>,t "nrurutic'• ratt3.v:^ n';s a"::rurutic° r.-pnrtsr wad tit.• caln),rories, cnwpntations a•crn lint rdri,v o:u undrr tho cc+unt,;6w nether phrnotncnun wV,dd !u.m tu Ix- cspluinad u, n„tku t!tr .rlf- rtalitf f!uriltg [Itr !m!r 2 U. s rt,,a,t:+ i! 21. it t+'Ul:ld ltr ntrMaar: IO rtiun hyNtiu+i+ trnablr: danu-h, t6r mnrkr,i inrrva+r in lun;;-rnm:rt ttt Is r:rtunily not ua•ui!nhir, sn•i: u nmrk•d rhx::;r pnd,ahlt• hn+ nos ac..d' durns Ihr +nnu• ,,•t'iud. Slthuugh ,!.:u:iticr n-i,lrn, ~+ or. :L'u mn t!ntt lhr frvqnaut•}•t,F "nrun,ti,•:' in tht• txtpldn:cnt Itns nl•I• in• okirng and orher tVwro.,•s. sueu u< n,rnnnr}' 1:•t••n• di.e,.n.,• end prptir t ia.postihEn th:u: the.'yt,•nrol[r" :raits nf e;eon•ar Nlrh,:i,•IM1:n:tj• hC t•:crylanation, in avhnlr or in pr.rl, of Ihn aavrriatiun hrnrern eiunrrttr - t-:nrrr. p0thnis that riFan•tto eno•kint i+ nr• ,-tiolr~i:•s1 furtnr in ltu:g nk:•rv nrn umn• •5tm:n':Ib••' rhln nnn.m,lkr. du.y.n:,t ~irrrnrl frum tllo :rrrti. On tln• hasis t.f pr+-rnl rvi.L^nrr. Qlc lnrl lhnt'rig.rotre . te stuokinF is Lto t as stmn;; as t5,• Snnrt•,•n ,•i;ntrrt tr -tno;ti::= :tora. . For itatanre, t11r ti'Writillun !TtnaOatt 1!,esr ,Iii1:L'VA un/i ?Itlt- , r, em•h of ,ehirh may lw• rrtnlyd i+t ansu• n:nuai•r m ry rriu,&:~i.ml • )_ With rtropev6 to' prptic ularr. iL is thu~u;itt fhal, iu 13ritain, ahc lumr r:w.rr. .,llrn, the inrrru.w of i oronan' urit•n• cieeasc mortalitprluti:mt a.+6•rett as tllat (,f luul; r:utrrrducrq; thr pa+t 2 tn a dt•ewitv ct:ec of ).mstric ulrcr has art:rn+rs' Ihal of dun.!rnal tJcnr . inrn:uaed. althout;tt'ia the r!10 =t:uLairal at+sociation a•ilh planutinn fur the aswciation of rnoptic 'arcr end avrottaq- discttao \eith eette• emo!tinL is ft•sa (fy ). Tl. r. scii-s.•Iw•ti~n?+a,r bt• It n•asonable tie xmokirr,,. Snediae of tlt:• n•Lltinl>:hip of rtantional fectors !n T 00;:0606
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py: •. f-ur.,ca•b„t...l, l•.i•._r nca T,.orn:r:,t..r,..rT L:,. 11.a.la.ir-I',L., _ n.ll'r,...aa..:,l.l.a.rati..n!'.-. Gtt Tnalurut rf Hrn+Irual tNemJrn lu u.arrr~l 1'n.IL.•..In=.•„n ll•tvE•.% ' Jan..l:`In. 61. The 6nri. Dinp,r,i, nnd Treulmrnt of IMHUSSI+. Irlcnun Jfofi,ln< .,n. :• -1 : N .T+..Inn. U6W. 61 EnolngJ nml Trcalrrvnt of Lowered Drslslauce to GI'Ver Ilr.pirnlnr,r in- fectton. FrACraUOnYrocrMfn7r 12, *1, 1033. 63. 1'hw/ntoal, and Cllunul Annenm,lw6 at Atben,sclerusls and Curnnnq Il,rart Disrn.r. Frdr.rnllnu Prnorrdf.vr 10, f!1 :, 1957. In1th PdLrrt lr• llnrnrn) _ 04. Itoh' of Ihe TAyrold In Coronary Arlcry Dlsease. Frvaccdm96 IV, fntona- /lonatCmrprersDlncAcmis/rq,Yknna7R38 Qo. A\ev .\Dnmach to ll.rperlenslon aud Atfer/osclerasla Federation Procced- h lve.18, # 1, Ala rch 1Ril). 60. ProPbllpxls of ]schaemk lteart Dlena b7'1Lrrotd Therapy. Tne Lnne<t, Auc. 22. 1A,0. Pp 140-62. 07. Arter/osclerosla In 10,000 Autopeles and the Poeeible Role of Dietary Protein. Frdrrattnn Proccedfnpe )0 #1, Pt. 1, dlareh 1000. (e'llh dfnz Ilalaenholer uld O.Tscherne) OR. One Paclnr hl Increnn af Ittochlal Oatclnema. JdHd 17d:Yr20, Ihe. 31.1000• ( a91I1 11. Ilnlxenhater) EO, p'hy Ikart ,Utarka Drcrensed In Enrope during lhe War: Fnt ra. Proteln. Brd6aflnn 1'rocrcdixps 20, #1, Harch 1001. (trith 51. Rnlzenhoter) 70. Prrv nlfnn +md Ttrahnnat af Cnrawq IIeart Dl.mnre• 1'nrt I. From a 8clcn- tinr fixhlldt at fhe Am. Dled. Aseoe. Mr.ntln;, Deurer, Colorado. Noe. 24. l0ai. 71. GiroanrJ llrnrt Dlsra,e: a Prerentabte tlelabolic Dlsordcr. Acdcrunon Pmccca/aw2l, #n-• Itnrc. Apnt,111o2. 92. Coronnrr 1lrart DIr•rn.r: A Nelabo0c Dlsorder 1'rercuted be the Thrrold ltnnnnne. li.rcrrp/n liedlca• Inlernnuonnl Con6rc.s Serles id& containing a4yrnclr nf 1'reo Cwno.,un,lentiuns read nl tha XXII Iutensatlonal tbngrsss of Phfrlnlnelrnl ~ciena•x. f.eldeu frlnlhmJl, nept 10.17.11Mt2 73. Prevtntlon nud Trenlmeul of Coroonq ficnrt Dtncaee, 1'nrt II From a Selea- t10e F..,hildt nt Ihe SS I I Internallonal lbnOrexn of Phratalesleal Sclencea, 1.¢ W cn. Ilollnnd. SeVt. 111 .17. 11K?. 74. lln.e Autibinllra lndirronp lncanw•d trentt Atlreker FHOrdfor ProauQ- fx9,r 22. ',fR, 1003. (1rllh llex Ilnrrenhofcr) 76. Do 1'cmale 5rs ilor.nmms I'rereut Denrt Atlacks? Fcderaf lon Prnanad9q6 28, .'1, 2, llar.-Anr..1nM. (a 'IW Mnx Rntsenbufer) 90. A I'rnenrnl Diet for R'elrht ltwhmOon. Acdarotton ProecMtup. 24, #$ Dlnt. _, Anr..lau ,: 7T. ExDerhuentnl Thyrold DcOclencr Iu Ualue. Preseoled nt SRISI Intsrautbnal C Crnrgra.+an[Ph.alolr.glrnlSckneesTohyo,Japao.Se0L100s.T--vt aJ_ C Apr 1M10 Mnt r ^ f4- u 2 d0 / F ., , , . rorer ,o on ernf - - 711. 6nscePlibnfty to Infccllon nf Ctetin tllelne• FeduraBon Proeeedngt 20, #2, Cruen) - D C 11N17 (nilh I) -\ 7 1 • . 1 er P .-•. 60- Why rdmpnSaunn, i+rna CS,nrer and DlTocurdlnal Infurdlnn7 From a Seten- tlll< 6zhlh)t, Amerlcna Arndemr of Oeneral Practice, Ddlne. Texas, Sept. /s-_L Inm. 8L 6neMV116t111F to Tuhereutusla and Ilne Rising luddence of Lung OaaceR lTarraflnx P+'ncccJiuy.27. ,'fR, ]1ar.-Apr, 100.A 88. Th-rroid ThernpT nx 1'rnphrinsla nnalnet Comuarr Dlsenae. Pre-venlcd at S\ir Imrr,mtinnnl Cnnrrees of t'byelologlnl Sclrucex. 11'woL P/• Prnrredlapp of the fnlcrnntfm,nf U+,fon of Pkpdnln9/caf SN"ttf S3. Elrhlceu-TeAr Fnllva'up en Tb.ruld Thetooy lu 1'roil hrlaxle aud Trcrlmtat uf Cora+mq r'b:ea,e. f'rJoailoo P+omdln0~ °-•°•• ,][ar.~-\nr., 1011.9. ?Ilr-e.ln-ruro:r.n. Our next. lritness is Pr. Irving •Leidman. SVelcomo to Ihe rnulomillrr. Dr. Zcidmuu. IM you have a llrepnred emtemeutl Dr.7,r:lwtlN. 1•rs•sir. ' \Ir. C.m-r.r.ruaJ,. Is it. rcr,v lnng L hr. 7slrol.l~• To. it is nue of tlto shorlcr ones I think. ~Ir ~.crrannt:rn. Fine-The nnh• rensmt I nm mrntlnnin~ it ic Ihnl I 1017 is .clting Intu If yourare to prv=cnl. yuur stMemcut I,o Irill be glad to reecit'o it. STATEMENT OF DR. IRVING ZEIDMAN, PROFFSSOIC OF PATROLOGY, UNIVERSITY OF PENNSYLVANIA , Ih'. "/,Eloltert. 11ly nAme is Irdn Zcidlnau. 1 grndunled front lho University of Penns)trunin Schoo~ of Dledicine irl 1911. lfter ou intc.rnshi') mn1 4 years of ser.ice in tho Army, I reten'ncd to Ihc Metlicnl School nutl joined tho Depnrtmont of I'ntLoloFry-, For over 20 years I have been here in an academic position, tenching merlicul stu- dents about cause nntl oRects in disease, and doing cnnecr neenrch. I- am no.r a Professor of Pathology. Ify chief re5enrch e/forts have concentrated on the way cnnccr spreads fl-mn its site of origin tn dif- ferent parlx of the body. Trery Yeor one of my lecturcv to students deals, in part, rriUl tho relntiollshlp of tobacco to lung caneer.'I'helc- ` fore, I have made extra elforls to keep abreast of deve/uptncnts in this field. rl'lle fact tlsnt I am a smoker hns also slmrpenctl nly inteteslA in the icsue. I cnn stnnlnnrize my opinion in t6e tohacemrnuccr cmd.rvreasy by saying that the evidence pointing to smoking ns a ennse of llml{ enncer, is tncom))lete. Nomovel•, in exptaqsing fhis opinion to mcdlcal stu- dents--the future doctat'e of the Nation-I feel oblihnted In dn nloro thnn present the punely scientific facts. I ennnot ienre stuflenLS with the feelil>,Lg that tobacco is deBnitcly not a cnmse of Iung cancer, ns there is httle evidencu for this stand. Thercfore, iu presentino the issue to etndonts, fhe pros and cons are reriea'ed, and the follolring conclusion is then offered. Consirleriug nll lhn nvnilable iuformntion, it is safest to assume that heavy cigarette smoking mny bu e.cenk cnln:er-Prr.htcing ngent in a snscepl iblo lerson• O1>,mrve the use of the a'ords ".safest,' anssutne,u "n-eak,n and ".sus• ceptible.J"I'heso are hedging .rords nnd tlmy nre uscd purtlosel)•.1'ho medical students will be ndvising pnticnfs nnd families in tko fulure. With the nltol-e conclusion in Inind, the doctor cnn advise lbe 1Byenr- hl '~' -~ - -- o not to start snloking; thot e ma cert t Iongh 16 avoid tbo stnrt hn1'd to sto ilOd th nld , p ., c er hsbitnnl smnker may lw ndvised to stop or co)ttinue slnnltinir after .cei,t.hing po.ssiblo tobncco ]mxmds on thomteside, and-ou tla: ntbcr- pos;lble psvchologicnl distnrbnnees, viceigtlt gain, mtJ other ef(ects re- Infevl to Irit)Idrnu~nl frnm Inbacco.In short, if nsked Ihc qucr-linn: ")Iny henvr ciumutle smokin.- cause lang cnnccr?" I nm like thc cautious prn,iicinr ~Ih,qsicinu nurl I nnsvrr: "]t Inay.~~ Ifo,rcrcr, if askcd Ihn que.stinn: " A+es Iten.-y cigarette snwkinq crolsc Imq,r cancer?" then I nm faced widl a moro Epecific qucstion nnd must nnsvcr ns a sciootist. The InIfilPer is, "I cannot, tclL 'FLO evldencU is stlg(;estlve, but fnil9 short of beinF i ncoldrovcrtibin and cm,cl usive." Why all this hedging Ir)rcu there is so rmlch sog„rstire cridenco thnt. heavy cig'Irette smoking causes Inng cmcerl (I) Eatracls of smoko certninly ptoduce cancer of tllo skin of mice. (2) '1'he incidcuce of lung rnncur is rncrcasing, nnd to is the cigarette consurnptinn. (S) Peoploslnoking tlro or more pnelcs of cignrcltev n llnr hnce n drridrdh• .
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PIPE S\-D CIG.L2 SMOIiI\G The Rcpoat of at :upcrt Group sp{wintcd by . Aetien on Smoking and iL:alth . L 67-, Fou.ovcrsa the publiation of its Ietnt report, 'Smo3dn; and3lcaldt \osd in January tVt, the Aocal Calh~ge oE 1'hysicians of London rctt up an or- ganization to rafly volunttry• ctfurt in this ficld to supplcmtnt wlnrtcvcs• aetion nny bc takcn bc thc Dcpartmcnr of }Ieah4 aad chc Hddt Eduatlon CeuneiC 'this orgsnizstion, knawn ss.Aetion on Smoking :hd Iialth' . (ASH), reechrs many inqu'vio, amon; the most frequcnt of which are thato eonecmed with the relative safety of pipe and dc smoking compared trith , dguette smokul,. It seomed dainble to sunun__-+•izc the pracnt endeavnurs un the problem to guide inquirers and to help doctors in advising rheir pztionts An_tezpcrt group (u~hose mcrnbers are listed at the end oE this rspert) u•~s appointed to Ionk into the Question ancw. This reporrcoasidea . the direct risk to the pipe or cigar smokei s own 3ealth, the eftccs on halds.- of changing frtmt tiyryreta: to pipe or dgar srm:ing and the risk and dis-. comfort aused to non•smokgts who ae ecptsed to smoke produced by -. smoken in their immetliate anuoameao--to-e.lled 'passive smoling; . . Pipe smof:ingand cigar smoking are mnsieicrnE together mther thatt scparately becettac: the risks of thne nxo tbw^Is of smoking cre siutt'lar, •.their chenial cturaemristia cre sul••ilar, and bceuse in many m{wrn they • : _ hare bcem mrtsidcred together s the ntutdsets of'pute pipe er'pura' ctgpr emokera ixere too unal1 for seP=^•^= anai}'sei -.. , . _ •(I) TMA Ri>w TO THE 83i08E3t' OWN M6ALTIt -- ZSeteist•.odaubtthatmen.rhosmokcontypipesandcgcniutrermuehless ~ risk of injury to their health than those who stao4e dgatcttet_ . •• . (.r nYATM3 FRCA ALL CAC3L3 ' - . -- Many largeaan•e}•s have shown ihat ci;areetesmokcrs have bcnseen aSo and too per eont. grr.ter death nte frotuall caurs tlun noo-unoker.. Thcas . who smokeooly, pipe: or cigms have a mueh smatler inercare in rttost8t.: .. rsnging Gem.t per cent, to:o per cenL in the vztivws atudte Pipe or ci,~ . smokcra who rmokc moderately snd do not ir-ttalc have only a txty smvl ;. " ieettasa in ris3:: but ttte minority tslm smo.t;e heavily (to.n or more ci.-ars -, or tscenty or more pipes daily) utd inhale, inetar a risk to life simiLir to that . of ]igltt cigarette smoktss. , . ' Practitioncr, ;ay 1973, 210, Gd5-52. tl LUNC CABCEA . , - In fivc Iarge, forwwd-loaldng studia involving nearly oae 'mBlian pcoptq dgarette smekers wera (ouad to haee a nine- to (ourrcn-Foid inarase of. .. risk of death (rem lung cancer, temparedteitb aonsmol•m (H-^'^^nd md •AIay 2973 . Vot. zxn (643) . . . .. .. T 0020626,. TZHIr 0305604
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Tobacco Industry Research on Smoking and Health For t past two decades, hundreds of scientists have per- forme thousands of experiments and written millions of words in a dedicated effort to explore the question of smoki g and health. Resul : So far, in spite of this massive effort, there are emine t scientists who question whether any causal relation- ship as been proved between cigarette smoking and human disea e--including lung cancer, coronary heart disease, or emphy ema. They believe that years more of exhaustive in- vesti ation will be required to clear up what is indeed now a mu y picture. What a been learned is this: Establishing cause-and- affe t relationships, which have been claimed to exist by gove ent agencies and other groups, is much more complex than originally thought. In fact, even those who claim a caus -and-effect relationship has been proved admit that no p rticular ingredient, as it occurs in cigarette smoke, has sea demonstrated as the cause of any particular disease., Who sponsored the research Ther, are those who believe that voluntary health associa- tion have provided the money for most of this research. Othe s think it was strictly a project of the various O. S. 6ave nt~departmente. " It i true that both have been...and continue to be...active in is field. But--a major portion of this scientific in- has been financed by the people who know the most aboa cigarettes and have a great desire to learn the truth... the bacco industry. And e industry has committed itself to this task in the most objective and scientific way possible. • A $48,000,000 program In e interest of absolute objectivity, the tobacco in- dua has supported totally independent research efforts with completely n,on-restrictive funding. In 054, the industry established what is now known as CTR, the ouncil for Tobacco Research-OSA, to provide financial supp rt for research by independent scientists into all phases of t bacco use and health. Completely autonomous, CTR's re- sear h activity is directed by a board of ten scientists and hysicians who retain their affiliations with their res- pect ve universities and institutions. This board has full auth rity and responsibility for policy, development and 7005:0634 TIFL 0305621
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:S2 ucf_x;~o CGttlnCrf (!t*PSSi antt f.i',La' =1"or II4::in:pr]C!Y 3CGSIQ tJJ t'arr:£1 out in slxd furti_s !::i.t •xt Furtl:cr aaaicaa of dmsc ohtai:v.? ia tar ,:c>.•n! san•o< is in pro~~oa< and will iM i.'pArtC+l nt a Itt:.r datr. I: tio::td Lc of intrrrst to.LC:c::aina if ta•r.• i, nt ltrr iarme oi (ubncco c;v ar.c e:notiJncl faclnr.. lldtrcU:!uLLrl}', r:.utrLrd ~•)a.pa:ira!:~, :milar to :ic ouc tacc in t6u rrinr•t. e•rn' ent i:o,.ib!t•. a: tht• iatall tu:mJers, ar.1 Q,e dnta will has•c tv br onal:: xe.l lt.v oi r•r tuor.• rorap!rz mel!lo.ls. _tL<o t!;r - n'httlntUlllp 1. t•.crru .'_:<or+ tt*•! in n:c:c•.•:n;:. sarit ns >FOCfi e::, etC., atul +nlooiC~ l.nltile c;Ni r:::n:Nt:;ai ix•aon i. uC iacn`st a:d ~ ocir.e naalsZpl. - ' - I:efrrtr.t•e~ - (1) QsAaeos. J.: G•o)wh:,c nt! laag ca.n.<er. 3'.,cso ob;rr•st:.ne nc ana rcec.:: rcry,rtw J. Atn. drat. A..,c. R3: 'h-35. Utid• . . (9 Seut•v.., I.. :.I.: Cn4! inpiy-aa rpi:n::::ub.eir appanca.' L'u::. Cn:c. )(ina. (laapr-k 1'i33. (9•1 Y1TP:•, F.: 4.a:p!ia't =nd't2. SCr• Tor:, llnfturl•ub.CO,u11:i. - - 11': \., atn! }Luow, tt-. C, ; 1y:npie 8nrrec S!e'b.v!n aml Theory. )&tlwdn nna ,appticsttinnr. SeN Yor:, bwn 1t i:r7- @z-m.n, . (ue., 1033, rnt. i. /C;S pp. ' " .(3) BToema, i.1.. « M.: \!,:,au:ntrtet wtd Pmli;t!wt tixndiiy a tntial t»y- . aholuK}•y in World War Il PriurnWa 1 nir. - 19311, vn!. 4. (6) Contas, lF. G.. antl C•ac. G. \I.: ksy:r!ronstti ~{,+rl;tns, 4nd ~4' \ev Tod:,. - Jol,0 tCiler g $oo., :nc., I'-•." P. (7) $.txsame. P'., aM 8xtr:::s, df. $.: dnwki:rn p•r•1.•r.e aad epidcnialn>;y of . 1uup,cmeer in th: G:ioa 'Y.tw>t: Arr tlrc uumpatib!r'. 1. Sat. Cwecr Iu2 ' 1G: lilT-li{1, I1t5G. (S Fpnx• P.: TL'n ml. nf at:mtenlleic , uIL•:t!on in :h. pithtqeerolruf pwyum.~emrtcr: ,t ATirta Csr.e!t Iloa. 16: 3?5-393, 1036. (8) HC.rn, C. 1C-- f7Rh•:wu•> bcareen r;n•:krts 4ad nuneaok"• d.1f.A. .1ra§. Int. )SCdL ltlt: 37i-35a', ip38- ' (t0y Coa•nruao, J.: A mcthod af .atitvt:in;t ruup n.~:i:v tat~ fvm Applien:!un in nn>ar nf ti.• !n8• Ln~t, oad crn•is. J. Sat. Cauue: lcst. t1:.12fi9-13"ib,10u1. - - (Ill li.x>an.o, F.. C., nrnl 1L•nx, D.: 3nto'sing ncd deuS atea--rapo::.or• f•ar•y- fots fnontS><of fulin.n.np o2IS7,T53 mrn. J.d.3t.\. SBa: 1t30-IG2,M4- 13p8.1933. . (18) Dotta, 11. F.: 1[orbi!&, anu :aor!aliuyitnm ranret at 1•e luttx In tSe Seesi 6tstee. Ana Luin ic: a:aL ~,ntn c=nrnttr. 0: 1SfrIS3, t933. (13) Leo, E. A.: Smro i:ut.''+tvae ef nosttx!itp natistiea re!at!ag tn covnan' artery A6uvn J. D'w r.- t.J-"-d9. l!/3T. - . -(1<) Dutl. It•, Jna3e, F. A, .mt PY,nrr, P~ Eflor.of sanhice ua t!teplwt::ct:cn ... .- and mainceasxe ut aaS du•:•4sr.a1 a(cr... L+neat 1: t4+:-M::. t03S. { TIFL 0305579
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]fl.rvi 1)r. %c 'vt! a. Sir, I Lkiulc ,Ynnr qne9tinn to Lhe previous witnc~s wns ur o4 hn:. ~I f intrruuro tcns n~4:16 pcru'ntiltto of nulUl*+nty lun dunr, in husI'ilals. Al lt 11! rr"n.v. 1• e+, ci r . . 11c. %I:In:,len. 1Vbuu 1 uty Iru pcrcrutt I nm talkiug about pcrcr.ntago af uulnllsics dnun in nll drnLhs iu Lhu cotnttry nntl mlury of IIn:Sn IN:oplc n-hndir.oulsideuf LltehuspillJofr.vmrserkrllotgel:nnynulolr.ly. Mr. \V.rrsuv,'Phal n'na thu roal frgnlv I was Intcrtwtod in.'1'hnt is yonr figure :uld uceordimr to your shtlelnuut uoly about 10 percent of u11 denths, iucht4ing 11011! in nnd out of lhe hopsitals, are folluwcd by nn antoIxy. You cedninly mako it mighty cleat• hero that while wo lilst Lavo lltu relationship or nt least tho fact thrtt thc alpoltt and llm discaso noalr lo~ctltcr, tlm uthcr factors nro donrly missing and /hat is the corrclnGmt between sluoking and lung canect• in LIm aleGml cz- prrintrntotiay aud t11o proof Of tlu,f, uud to We you Ilrrc prWeltted a Imgldycompcllingnudcanvincingargumont• ' , I would only nule In• (ako exception to one gttttolnent on your last pnnrgl•aplr on 1nlgu 0. In tho secolltl uetllmce you say, nlritst, l.o ntd.ey tlutt tho can,ntirn trgent mrd the disenso rrccarring togethcr" I think if you would wnnt to Iw totally objoctivo ubout it yotl wonld goy first hc notes thut tlw sllslxxted cnaslttivo ugmrt. If you know it is the rnus- utivoapentnrby 'rrur.cotl W tlronczteWpi • • - 11r. /.Innar.tx. C1:9, a11'. • hG'.1VA'ISnN.'Chank yoll,hlr. Chairman, ' - 'Che (hf.ululAN. Mr. 1'rnyra• I ' . . Dfr.l'Nrut:u•,lutt.l.rvobrief t limis, lka'lor. . \Yo havo luul a discus.viou ~ur_sInto oadiot• of cxtlerts on tho subject of whotlrer you cau tell smokors from tho nmrsmokcrs hy oslunininq the Jmtg. You arc INnft'swr uf pntllology ot tlle Unlvcrsity of Ponnsyi- vr1111ni Dr. 7ecmarAx. Ycs, air. ' Mt'. Pl:crer•. I wntdd be iutcrested Ingc ttin~ yonr opinion on that, Dt'. As I undersland it, ynu Ilnve2wo lungs in the hmlds ilntl ynu hwk nt thcm and by the pIgltlcltt nnd so forth you can say this IlelonRa to a smuker unll this does not. I also luulerstluld suvcral OiAllusaidlhcycollldtclltkis. • - ( I\vould rslnna u ut u . .. . would s:p', n.l conld INIt lull II nnd tlm nilmr twu would eny,.rrl cnuld i i i v no n- lcll;!t nud lhut lhosi+ two w1m could tell either llnd eoma-d tuilionurwcn:nul.tcllingthutruth. ~- . . klr, 1'agvrx. Yon sly of a LbottsAiui pathologists you would guess - . . ''. .,1 . . . 9931 ])LZ4:1ntlL\N.YeV,tin'. Mr. lrlmvkn. Su lha'n is nu discoloration wlsich you saw, no turning black. pr. '/.laonr,tx. Disc'olorulion is not related to smokine, but is rninted lotlnstiulhuair. '. . ' A6'. Pm:~'ut 00.4 wonld slty you cwn't toll, and tlrcn yon used nutno istlhaL un tlm Inlllon~ot pngoti you etatclwhnt youl tlliql:~p oj ~Ittdo atnlc - 1 . ' - . - . \Yn]dd yog;;,•ty this rvoold ho 11 ptvla5o 7ulrolhlq of it algltrclto pnck• Ili!F.ur adtwltlgklgl lllleayy clglaY:tte g11WkIng.I11Ly tlo (L tleak cl]In1W' . . __ .: r........ . ly t.h:dl yonr jntlrum.nt Of wlmi, is Ihn must cNnct InImI ln put un u wntailto i Yolt.quuic t4i.9 in yuw't.nl ituuuy. Uc. TaundN. l•'ur WRPrlin•,r, mrINIM6, r\II•.1'cr:reN. iJuuol.ntr:m[Irni.-..- 11t•. Zr.loalnN. Wcill I tilinlc tlrlt is Ihu Lriresl J;dclual6 that can Iw _ m:ldu although yon uru couccrurll Lcru only with cancer. 1'cs, sir. AfnPur:ren.'1'hntworlldbonGrirul.LLcmontl 1J1'.zT:II1nL1N.!]'f9jsil"` ~1it•. PNCYr9t AII rlght.'.Chllllk yUll, A'N;lor. 't'Im Cl1nunwn. '19aullc ytiu very kindly, Ductor. 1)r. Ir.11rMAN. 'I11a111r yoll, sir. 'I•ho CunulanN. We npin•ccilrlc ynur cmuin'rmld givin., ns thc bcnc- frt of your tJrinltinp,. loa Intow it ix nu'ftd lito hcre tmlight mrcl rvo almost havo to Iqwlugizo fnr rminiuit so hdu but n'o run tryin~ lo accommotlnte uvoryuuo that wu can nnd wn npptrr-isto your leslinlony. Dr. Zntnrfnn. Inp neclatoyonr givingmeyourtimo. TltuCrt,vnuAx. T~Innkynu, At this timo I uvrldrl liku to plnrro in tlte tccord ot stntrmrlrt b•v Dr. Lymmu A. llruwer l I I„e tholncic xnr],n•on n nd profc.cwrr nt We Tfnlicnl School of Lonrn Linda Univctsit.y iu fAn Angclcv. Ile lnts In nvLJut1 n sttttemeld to Lhe cnnuniLttro ou mcdicul nslrccts of Im' nnd nicoUnr•,. If thoro is no objectimq Dr. Ilrovm-'s slnlaumd will bo itlsl•rtr•tl nt tll is point in tho lccord. . It is so ordered. ('PlloshttulnwltofDr.Drewel• follnws:) 6YATCnIrNq er t)11. LYYAM A. IINMW.Jt 111, :1'Irtn1An10 4UY1'IUN Alrll rr.rWrYwux AY tnY a1rLmAL 84.34006 er rvtrA rJNnJ UrrrTb YIYi, tNs •tNnCIJS4, IiAr.1P. As n npeclsllxt In tWeares of tkr ckest the wrltrr 4ns Inmle,l Inorr Ihun ntlc thonsmNl cescs of nrpultry enrclnuulu or Ihc luug.'lYds eqa~rlrnrc Irns rrurrnlrtl a greut In1crW t In l4e lruneudara Lm4lvprn Vn'^rldcn by 4rm,rbogrnir rnrclnnum. neclnrse muu euonot be used ss m, cY4rrirnenlnl moAcl for t4r Inlrn6lvncbinl lu7rcllor' ot ysrlaw 7oasi4le cnrelnoqrry Ulcro Irnn 4cen a nn4vut uxe of h1UurN- torr onlnnllq to tlCterru4re wh0lher or uot luna enocr cou1J Uo pmA1mN Uy thr lotrotluctlort ut vnr'loas anbaolrceu thungLt to Uc cnrctunqr•nlc. 6ndr e¢ncrlulcnls nI111vA:A "samking unuhlnes" to collect 4rrv nnll rasl,Lui, frn+n clpnretlu soN•1:••. 711e.rn su4rtnncoa c'cru tlu:n rVl'ltcd tn Ilro rA91 uf csr"rlwr.nlnl nnlnmlr h: hi'4 wnlceatnrtWus, Intnil Illnher t4en It 19 urrr Ilu.,xII11C lo Illhnll hl Ihe Inng nf mml by clCnrrlte wnohing. dfler lhe IqN'llesllon nf Iht•sr rnuAe cantenhnlrv un lUr. ikln emlccrn rrr•m nU:•rrcrd, '1'W.v d/iarrnllou Uue becn antluly eml'IunAzcll. Uolh ,1 Iln• I)u trl \ n,v nln abroutl. e. n druuNralrnllnu nf Ae/llrltc Wunf 11nA IUa I"rn nnd ruaWurs In rl_ u- cllc sulukn producu prlmnry bnlucbnl'rNr cnrelmnnll. It In n4vlnua Io nuy -•Iru- Ilst rrlu/ Innku Al Ih,re rxrcrimrtpa nbl"''llvrlY 14at Ibn unly 4.rt 4rorr/1 /x Illnt very hlglt cuurcnlrulbnn nf rlgnrrlle mnrrl:e 4'..v Ilull rca4lur.v~ If yl:lrrtl ulr IUO sU 41, nlny nnldnre JJn unnccr thl cx VI: rInlrnlnl nnhnn iv. Ponowtng I41v d'•wuustrnlton thnt ekln enrMrr enuW be I'ruJuerrl lo t•~Vrrl- mcnlnl uulnluls bY l4o cstcruul nVPllnl/luu of tnas unrl renahlur Iron, vlNnlrilc tmoLq farther exprrlmenle were cnrrlrtl wtt lo nnemnl to prore .InJlnrly /hol carclnmmft of the Irnchtbrotu/nnl trceN co.ud Uo Vruthlrcd 41 t•~Vrl'iniryl4d md- mnls by Instllllng these mra nnd re+ltlurN tllrnclly bltu Ilm Irurllen. Drspllr carnc•vt antl cnrefnl enorts, nle tclN•nlyd nttcuqAS by vnriuun b.rrsli••ntola le ~ ~ H r~l r O O lll IP t0 0 rrnlloeo UruntlmSenle enrelrlonnr U~ Ihe Ietllllatlon uf clpnrcUn sv"ul:c lnrw nml Q' [ukWucs Into 11" lraclmub+oncUlnl lrrn Uuvu i.tc•m m~mrrvs[ul. 'r4nn, nlanlel evidencols UIc4/oy lhnt I4r bnrnln'chunl yd'olubtrnNlnl of lur. n.,.l rra- durs .frtnn eitinrutla alooke rrlll runldl Itt cutnlnIrut ttnp ol•Ind/lea WrulnrUwl oL tmchcoLronNdnl-pldmonnry emucr In csprrhnonWl nnhunlv, cr.•u nUen um-lro llo.wlu ot thrnn sn4Muucci ars r/nplnysA.'1'hrnu n•yulla huru 4mn111w ennm .,llrll"r t4e anbstum.CS 4nro Leeu Inslliled at l4irrnlfa ur nrlro nerk[y urcr n IK'"loll of
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-2- diree ion of the research effort. Each researcher receiving a qr t has complete freedom to publish the results of his work, whatever the results may be. As of this year, CTR has de grants totaling about 26 million dollars. In 19 4, the tobacco industry made a comnitment for addi- tiona independent research that amounted, during a ten- year rogram, to 15 million dollars. This cosmiitment was made o AMA-ERF, the Education and Research Foundation, an arm o the umeriean Medical Association. Under this pro- gram he ERF, like the CTR, made grants for scientific re- searc with complete freedom and autonomy. What they did As o January 1974, the Council for Tobacco Research alone has arded 480 separate grants to scientists in about 218 medi al schools, hospitals and institutions in this country and ive other countries. Duri g the ten years of the Education and Research Founda- tion proqram 222 grants were awarded to scientists in 87 medi al and research institutions. Whil the projects of these researchers may be considered rela ively aarrow in individual scope, the industry has not verlooked its research responsibilities in broader area . In 1970, Washington University in St. Louis an- noun ad two million dollazs in tobacco industry funding for tudy of immunologic factors in cancer. In 1972, Harv rd Medical School announced receipt of a 2.8-million- doll tobacco industry grant for a five-year investigation into pulmonary and cardiovascular diseases. And in mid- 1974 the UCLA School of Medicine announced a 1.7-million- doll r, industry-financed, five-year program of research on 1 q defense mechanisms and early detection and treat- ment of cancer. Tha omhined co~iUnent by the tobacco industry for all thes projects amounts to nearly.48 million dollars. In many years, the tobacco industry's commitment in this area has exceeded that of any government department... aad as aome to millions more than the research expendi- ture on smoking and health reported by all the voluntary hsal associations combined. What they found The indinqs of research studies funded in whole or in par by the industry have already resulted in publication o! 1,850 scientific papers in professional literature. T uqb this work much valuable data have been produced abo t lung cancer, heart disease, chronic respiratory ai ts and other diseases. eowever, there's still a lot more to De learnaa. • T001:0635 TIFL 0305622
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SI:IRN'1ll~I/: AI)\IS(/IOY Itl/\Itll I•, llr. (~our,cil Lalir.curlr -11 [;\ Inc .r.rl l)crauhtr tI. I'r7A SIII'1 1)I)N 1'. SOn1Ml'NS, ,M.1). ('1r,.irnnor birn nlvrnr.oiri. I.rn,•< 1 hll 11•.<pil:J ( l+rrirrrr rn~r.~.,,•r r,j rrnLr•r•.v,' f'.•Iktt nf I'hv<ici:wc •E Sun•cnnv nl (1•lumhia l Iuivrc.iIv Nct. 1'r•d. Ni-..- 1'++i k ItICIIAIiD M. RIN(i. M.P. nn,vmr.•/frn.li,dn••r rrnJ Invrrrnrrrnl ntrrli• inr 1lunlim'lan Mrunrri:d I Iu,pil:J. I'aurJcn:r.1 ;difnmi:t 1Sn/n.orr r•f MrJirinr . llnitrrsilv nl Smdhcru (";diforni•t Schrr,l uf Mcdieinc I.rra pnrrlec. Calilornia IOSCI'I 11) . Pf.LDMr\N. M.I). Rrnd.l7cpamm~v of InuuunnhNhrdn.•c Scripp' ( linic :rnd Rc~r:v:U I'nw.d:uiun La Jdlu. ('alifornla WIIJ.IAM IL (iARDNRR. I'H I). Srirrrli(ic l)irrr lu4 '1 I,c C'rnrm-d (.•r l••I •.n,• • Itcxorc6 --U $. n.. Inc. N. K. fJnm l•.ulrn.n -•/ .1r..o,.- n•n••rrui I Yilc llnrvcnrlv Scl.,•d rd M.JU.nce Ncw I I.rvcn, Connccn' ul ROIM-RT J I II1f.11NP.R A1 1) (Ai•i. Vir:d ['artinr+terw~ria Pru¢rarn Nafir+n:d C:rnccr InHrwlt Ilalxsd:+, PlarcLmd LGON O IA('(H1SI)N. M 1). /)enrl uJ ILr Ai,'irirn+n/ IfinlnYir'.rl.S.ir~nr'r.e !L'A.wain!'ruptcvrr n/ rtirdqcirnl Sr inur+ (/nivr•dr....f ('hlca:v. Cl+ica,..•. I Ilitx.is n V PRII.L. A. 1.11iHr) W. M.1). /'rn/eavrr nnd ('Arrirmrnq Ikp:nm,eal uf 1'alh.dr,'v llnlvrrrily ul (~allfumia S.'Lnol.d MCJidur S:rn Diren. ('aliLnniu Of_NRY l'. LYNCH. M.D. 1'rn(r:r.t'or rrnd ('lwinur+n DrpaHmcm uf Prcvcrtlivc McQicinc ~nd I ub/i.: lloalllr C+righlrrl Ilnivrnilp Sdranl uf McJicinc Omaha. Ncluaska I VtNS Mii1FR. O.V.M_ Dr. Mcd Vrl.. M.K.S.I1. ,Fv trnll Srir.rriv l~hc Jackvnn I.ahor.rhrrv Ilar Ilarhor. M:riwp . IONN I'. Wvn'I-I'. M.D. Pi%rrro. TnLacto ;nal Ilcnllh Rracardt In<IBulr: l)nircrsilv r,f Krnlucky Lcrinrlnn. Kcnbrckv Rrirnlifir ti1nR uf Tlu• /:r..ur6l WII.LIAM 11. GnRDNER. PH.D. $r'irrrlir ic !)irrrlOr ROIlERT C. I1OC K F.'IT, 1'H. D. Rrserurh I)irrr Iru JO11N Ft. KRI?ISI IRR, f n.l). PRL:DGRIC W. NORDSIF.K, Ih/.D. A.cnx'iNr Itr.r'nrrlt AirrOrr il.rmrcintr Rr.rnrrll tlirrc9ur DAVIDSTONE. PH.D. VINCENTK I,ISANII. U.MD. ApJfXiOlr Rt'.srMl'/l /)irP[ Inr Rcrrmclr A s.nu inlc TIFL 0305626
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646 • . TttE rancr[rfoNEa. Ilorn, tql3; Uuf! and flifl. 14154, Rest, 1966; Ifammend, 1966; r::hn., tq6(>). (:y cunq JnYnn, tuc iuerc•as.el ri:k (ur plpe anal;vr u~ar unukcrs u1i . much stnullcr, earyin; from the snme-risk iu nnn-smokers (Ilatumond and. Horn, tq;S) tu;! timty tlut riit (Uoll, rq;_). . - Recent Swiss repu(ts (;lbdin and Gscll4 tq6;; CseB and dbclin, 1972) Lave becn interprcecd as su-,;esting thac p;x and cigar smokiqg nuty be u dangerous in relation to lung ancer as 6, rctte smoking. fn tt>rscstudin, hotccrcr, only hcaw, pipe anrl:or eigsrsmo{ang nm assodatai with a high risk of lung ancer. The Hndings may also be eritieixed on sercal grounds, chiefty because they aore based en srnell numbers; pipe and cigar and . dgarctto smokers uure compared without strict coasidendan of the ansounrs , Ciwth OamMCUS Laqruc Lwe KsrnmrYW 4 . 3. 30 . Pipeand;atepn ~ ~ . enty • rt. . s a 47 Grar.eu.edr re rf ' 23 tes '.T.urs 4-Tnn~d dorh roro mrw.mu milrapd 6f a N Y~ reweme.eso[wieu.wolYaln.r7be). . ' srttoked, and smoking historfes, obtained fnm ineenieu: aith eeiati.nea o(' . deeeascd srnakcis, may not h3rc been aatsrata Further the findinn tmy not be reks•ent to British srnok•ers, for the Sv:bs tyyo of e5„ar or'stumpm are different front thosr usualiy smuked in this country and the smaltn is more often inlnled. . It is reasonable to conclude from proan evideacc that light cie r or pipe ~ smokirrg (cnc or nrn cigars or up to four pipn n day) do= rwt inacose the''. risk of tuns cmeer, but if consumption risu abo^ this [rna an in==xa1 " . •risk in eneouneere.d (tS')nder, There is no doubt thac for equat.- '. amounta of tobaarn smoked the risk of det•doping lun; anecr is much ..' . greiter for the cigarett,e smoker than for the pipe er dgar smokcse- - . ' - ~ ' Clu) OT714i CAnCSAS.. - . The risk of developing oneer of the rnouth, awpbagus or luyn.e is rmtelt.; . 'nfeteasedbyaifformsofsmekiug.andtheinerascissimilnrforpipeand.'oe .• L'- cigar ond (or t:igocette smakes. Yhe risk, houe.zr, is not cmrir u gsvt ds -• that which aanrette smokcn run of developins lung etncv_2Ttis is sbon;o ~ in Cble I frotn one latge amcrican stud,v (ICahn, eqG6). ,- . _ . In Britisb nten, death ntes from aoeer of the mouth, oesophagus and .. larytur haee been falling over the past forty yeus, dapite m incr+ascd mn- . sumptiwt of tobaeco. Although ci;arette smekin~~ mpidly inereased bMSeen , . -.. _. Igoo and tW, pipe and eiyne rnasumption stesdily felLLnptoeed trtaueettt 7 may have played a part in. taducing the mortdicv. but pcotubly We doan-•-- ward trend mainly rcBcetsa rnl nvuctioo in iuddrncs, siocc the registra- r:-. tiou o( aew eua has a(so beca dcertsaing.l7tcre Hzs abo a npid reductioa "_
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! Organization and Policy The C'mrucJ lor Tul.acen Research--U.SA., Ine', is Ihe spnnsoring al.Kncy of a prupram nl reKcnrch into questions of lobacm uve and heallh. II is the ourgruwrh of an orpani¢ation fnrnscd eatly in 1954 by represrnlativrs of tobacco mannfnclurers, grnwers :nrd wa¢bou.cemem. Hesearch supPnrt has b«n mainly through a Prngrmn nl gruns-imaxl mpplcmenlrJ by rnnlrnels for research wirh inslimlium xnJ Inhonlnricv. '1 Ac Cmmdl does nol operate any research facility. the Scientific Advisory Ilo.vd lu The Council meets regularly to evaluate applications for granls-imaiJ and for conlrncls, judging them tolely on the lusis of scienfific meril and relevonc<. The Council awards ¢ecnch grants to independent scientists who are as- sured complete scientific /recdom in conducting rheir smdies. Grantees slone an responsible for reporting or puhhxhing their fsndings in the acrepled scicn- lific manner - through medical arrd sciennfic jnumals nud sociedes. Another dfslingushed scienllst joinrd the Scientific Advisory Board in 1974. He u Dr. Joseph D. FcWmun, Head of the.t3eparlmenl of Immunopathobgy at the Scripps Cliuic and Research Foundation, La Jolla, California. Dr. Howard 8. Andervonl, a long-lirne goard member, resigned during 1he year. Through December 1974, The Council .pproved research projects for 323 iqvesrigatun In 223 medical schuols, hospitals and research institutions. These awars6lotaled more than $30,000,000. TLis Report Includes a brief summary of The Council's preseot program as well as lisu of the current and previous research projects supponed by The Couaeil. Also included are abslracb of 92 research papers, acknowledging CratneB support. Ih.f were ptsblished in scientific joumals during 1974. Projecl recipients have so far published 1,262 such papers. H. H. RAy.aa uman a ro 1 9 7 I 1t IC I' 11 IC'1' nt 'i'111': Co11N1'.11, FI/It IUItA1aY1 Itl'SP;AIt1al-It,ti,.l„ br., '1'11h: t in Nrll. Pf qt '1'1116H:1't/ Iti(V Utt I 1111~.n.1 :9th Glr,.r.l. IV.rs. York. N.1. 1//1/L" TIFL 0305625
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276 .^JiSCeItCGC6u3 KrouPirs aR'CYtCr IrtYll'bAC3' of 'f"L-::::(•:,C~'. ~t .: ItiLL:JI!C~ ICPC! oi hv :c+_a .03. u'1_ Acelpais cf tSn r...: •,.I:ir.I lusi '.' n•:I•rdi:Pl•:: nru br,tWCr.l :4nON:ri . -.tll •+i RY: Icu >ISf:al:;a!1)' siguific:mc nl n In swumar}•. tct-r n~,wrr.l.+•tia~rett+r•tawvun~partil+n;rr<-•e~ mort: fn+quc::avu`uLjLti.n:r.rc+puetd'ti:aan•si Ru`itt•rs d:+, un ubsen'utiun. ; lilCMla.liL,l r 1t4fro:L K L- AU~ CpU t vy_ lI t .. !`:.L Clfa3DRhi. ,:-~ ~cet'~,~s`u~•ayemei~i5~•~ •erlr.*%wrhf•~r •tate-:hsr ~ir.eri{ta-seunl..i~'are.--~ . hliedicrindicniunLi:iie:euc+ai•iokrrr__:; . . . ~ ymolGl•ra :tL1I {In::.:n,npr:: 1+..1.•• :•ntcicil rt•j[.^.rl: En bthlr d:~~rsl~• lt•rLilit•i, nd1rC;}, rt:!i, I ;iu::, nl3filnl Lirtltplaa: nf uan•nL<, ,tila'YLIOn. :Wra^;;. .4 L^n1!P`r nf Iltnrn:h•I-, ntaltnCr Jf time• emp~~!o1}•cd, nu~t~r.hl•r t•i L;lefli:alr:::il•r:. ::.calnr of <!i6cr1•rlt cici:~ or to}Yn9liCry in, nRr44nPr ra.cirt•d dur.lt11 a IJr.^.t.uti: I:or!•,I pr•.r,iin;; illl,.r~ia+r..ud .^.unthcr of \-rn•r or rnJilul: lrt.,:tu:.~n:_ d:::L:g _ li:vtilu.•. 9•!1:• n~R!t+ or thcsc . cot:tpnrisuu, urv prc,l•at.•d :a ib al:d 11. No Ji/rrr.mr.~ rsial to nliFinrr. mIR•irul atnltt+. :L+ lu perenta' Lirthp!nce, it ii Id :,::,•rra th::t a ai"'niL°ciUUiv 1s:grr pmpnruon of purrnte of nuu+mnk•~r~ v.-r,• !Haa out~i,I: th: Vnithl atnrl-r. Tl:r memli:y; of tLL+dilf,•n•vuc rl:d sr.u,::•r: nitil n+lp.vt tn l4r frt•rlur.nril•s of ntarria6r• otc. (tnhlc I I: :.uiirxtc r;::.t i:t r:ntnhcr of tlnua ,-n:pEo.',`d, number of times nnarr•.,L as.3 r ' 6u=pitrlixu:'a,nc, rins•{-,;: zmokrls u.cred nursa:n;. r: lutt!i=ntoW f:n-:d' qu.ntl}'th_ne("noc:ini,6 ri:.ttnrC~c'.ri:rv,lit rcnrl_twtrei~-g,4tr_o+whas..r stutwtico:aignifii•Ir.evlr_d::. ..~;I~.( indiat;::us;lc S~~ny . t:Cllteltn4llpltA or r::RUnla vf nC ruWl::lt :raalltPn, rtK•OiC(•d IiLLrlitb a liftlima ~ Thr exrt•axt•s notl•d G:•r dl awi: r:criuhb:i ,t>•,:mpln~•Ir•e:L, . matrit4•^es, t•tc. tnat' I>,+ n+a;s:. I:: ,.itl: t!1:' nsult<nf tl•c 1'IRnt iur:ul,+tutus questionnuiru. ';p,a:pwi_lutumlt<.ehun;;cjuhsmnrn often, movu.mon• often. r•t•: Ttlr ,xl•IS• ramI,•r 4 !,tapitrtimtionh is oi inturl•st ru/l mn}• el.:.r rrllert.yac+tuntici•s4" It woldl! Lr Rf inlenxt to d'etetvtino the rrna)tu fu: thrs.• luut• n.•ilrcl elltcr , raportad asaoriutiotu bcttn.:l do_I-o.w an,I ri~•arrtlr snlokiut;: such an ane.lysii is in ptvgrl.y.i lutd :cPa ue r,purtt•:1 latrr. ~ in Ltir~r !'irirx . In epidcmioiogir.l stndir+ n! !rrg cuna•r. it 4.- LI•.m :'..-1n.1.tLat fttn~ eancer is more frequrnc ir: cs!,nt: tinnn in runti ares, (T). TLis W :ad . to the lt}pothru tL•st ntntl~p!.rnr pollutint. mnr LI• nn ct•u,G.r•u:a faccor ~'oozosna TIFL 0305575
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r PA - 000499 r , r: ~ ' J. cM1ko~J. ~~_ ~~! r, ~T<< r .J F:\Mlt.t.V. AND ETIUtc31It)L(KlIC ASI'k('T'}i OF (1/RDN:\RC DISFi:\Sf•::\\U HS•!'G12't'l:\SI()\ CmRnt.txM. Nr.uel.t. Tnuat.t.•t. M.D. tl.Tt>1f,Mfi, \10. /imll /4r D<pllr/M.+t .J l1rilsil., 7•le ld.s t1sP„rs S'tFwf e,f dlN:ai.r . ;j(Rn-a+rMl 6w MlLluat'Mn Det.0. 195T.) Tt1 11 E\I the rieinK tidv o( hp(x•ttcluiou and cnruuar} heart disatiuc in mle o( the most chilIlenging pn+hlemn in preventi.'c metlicine. Pkap,te the Luc that elu•It eurt[iuva.avLtr tlilla,ur• t;lux•k& nfnrr than half the dutlth5 iu thix t.ottntn- pnkt)'• itsorigin is littlc luMlcnn•d:uld.rt•srmUla•sR'inetun ('hun•hill'sdctiuiriuu of Ruwlia: ••It u a rithlle »r,lplx•tl up iu a mc.tcry iusiAc an cni);rna:' It h:u ', hMt* heen llMmRht that tr.ul»itnrc elulatinn o( hluxl prci+ure ur esaye7rc rtri- ahility uf the hllatl pn•xMlre were ecitfcut•a of ;t fxnxihk pnh~'l,er[vtnliec state. but not until the aludirM of hh.wl Imsvurc in arm,r nHiarrs b?' Hil(mau, Lcvq, Stnwul. aud \1ltitr was this nhten•:1[iwt a:Nahlishnl mi a iltuutl fnctu:tl h:txis.l••r 'Thl••v alal rtcllit+i lhc pm{:ulelir si);nifir.auc nf tr,mvicnt ntchv.ynfia ;uld of merwa•i{;ht?I•' Tnn>ieol h.•Iwn.uMhw. tr.ulaia,t tavhyc:lnfia, or nvcraci~ht• Isleh bc itrai(, n:lM fuunJ ln inrn:l:IQ the {xnbabifiq• af the I:qsrt(ca-clopnlenc (if 311}rlltlelI h)'{Wrtrll%IMt :NItI o( Qixttwl{ty nr Jenth from rnnlinvaxvlnr nn:d dirolx. Ot aJdiu<wt• it t•'aa tlvullxl+lrtlat that the prt+a•ucc of tte0 nf these lron• <IltitMls u:ns u( );r•atar imfMlnalM.t• in tha.r• n71n•ctM than :u+y, nne alrlno• whilee the pn•rt•nrr uf :dl 16rrr wa> a rin•tnnwauvc of nc+jur pn+gunntie xictiltiarona2. ' Thua uhrlt tr•mvaq hy'{n•n1:+nNm, Ir.u,went tachcnlntia, :uul ncrnreight were :dl prt..+n iu thc+ltua• in,iici-hml. thr r,tta• <,f ,Itllxrqurnt +tmr,lin.d hcprrteusiun d•:a twehr timas n: high a, amnn4 ahanr with uune of thulr trtita. - ThtTr• WtlrY rl•InMtKi'l1Va' ?II/IIir6 with Iittlilt111/M1Y imlxlsa.l hr the fsrts nasliLd/ir. T.. Iuc il <ras apycin-nl th:u Jet:.ii..i in(<xnmtinn annrernin} mws,r nM+n! (lMtnrp W:IS In\~fPl I•YLM• th<}p ta'Ulll[1 IR• !l rHllnlUll IY.Isii for f+n•l•aqltiYC tnr,auraw and th:u thar• dal.r c•wW la•vlti.(aetnrily uhlain.l mds• AI•ferr ruh.rc , th:u, m}ri dt}curr.llire pn..+..+ ucrc retal/lil:ha+I. •Cha•tt(an, n><ltulc oF fw~tnn - ahirh nmp 1..• .i¢nitr~.+al t•n, nr.+r. <.1 h)'{la'rtlbiMrMl ,+r Iv+nc+an- he.rt di.r:ue K:wl:lu,u~hml in 11>•M. mlJcr Ih.~ Illyartalent r.f Pa•.~inier \II•d'xilleat thr Jl.hns ~ IY.~.//-/arlM.tnewlftw./..11YAr~alYmnrT,+rtow,dl•w•r,•nnu•NwIMV•tlrrNyJ• IML. Vn.. to. +•L:r. IIVnM tr Ib Lmon.m . W t b. •••w. fn.m • M1•• rilw.lmr .•um••' n••..wM. nnwe Vt :<b 1-nhwl }IM- 1111•:ir Il..an+l ..•/,..• 1••Llfl -VII) \p•wIY: tYml. TYIw arN/.1M•• rnr r~p1,`T M1) .nMbw, lil.•nl. Y.11 IJIb .n•1 •~.+•pnq. L.I•,L IJM+JPMM~. nN':drn. \~nw1M /')anamLl l'utA• ya). 1'awM. nea. x•.1 •'...1.IruY. 11•1••ww I,m,W): Iln..amA 1~ 1/'1 \ 1~.~1\L-~:A. t'n.wl.. 4bnlN.~au.n: N.++•~s ~buTn.l.•1. vM.wA 14vr lo..um~. In~ Tna,.v In.lu..y N-aml+'C..nlmr+- ' tri T~o^=qFq9 TIFL 0305582
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PtPE AXD CIGdR SStOICINO 649 . it~re to vnukc riC.ttatts wade uf air-eurcd tuLacem like I~ipe and ei~r tol4.lcens, the rie:l: to hc:Jth r:unld be -rc~tly n.tlnn~d. '1'Lis .<treCc+tinn is b•ctI mainly on a rc-nttllfr lutr luug-canrcr incidcncc in 1-~acrn I:urcpcan ntris-in rarticuLr thu USSR and PuLnd-tcbcre such cigarcttn are sr{lakcd. In f:tcc, lun;-canccr dct$t rsus in these countrics nn: similar to nsn in ntost \t'atcrn countrilY ieisere d,~rettes, uudc of oven-cured aeees, are useJ (Doll, ]qGy), so tlut Ihere is no valid evidcnn: to wpport (st) DO CtGARETTF SatO.CERS ]r1rO SWITClt ~ I TO SSSOFI50 PtP6S A80JOR CIO.SAS . SEDVCE TIIB nISI: TO TllEtn ftIALT311 . Uhfortunstaly, there 's no clear answer to this question. To obtain the [denee on which an xnstcor cou1J be based, ls ,c numbers of cis;arccte eker3.muld have to he studied both before and for some ceus after they. . d nude the chut;c, togctbcr with cqual numbers who haJ eontinuad to . ka ci, rectes, and this itat not yec been done:' Some doaorswho hs.e stopped smo'sing ci=arctus in the past eo years e becottte pipu :nd.'or cig-jr smokers, but mest of thcnt are only occa- . si nal or light smokeo, so that in considering changes in dteir mortalitj rs~es it may be difficult to distingui;h the c/i.ct of the chanae in type of .. cL•ino frmn the ell¢tt of chun;wn the antouat smoketL On tho.[nsie oE . esquotedbyTodd(t47s)•aboutlvitthec~-ei~ rettesmo:axu$ottsed tolinhale at leut a fair amnunt still did so on chxn.ming to cipis - I.t tltat ean be said in the Iioht of present knoxtedge is that those eigar- : ce mmkvs wha cftsngc to pipc snd,'or ciCar smodia~ and smaka less to Lh~aeeo a•fd inhalalesa, arc likely to hat•e a rcdr•rn3 risi T,wse u~ha sr.~a~- as mudl tobacco as before snd contince to isluL_, are uoltk.ly to have ten ns - ond luay ]rctt inctewc the risk to their ceal:i:_ (tIl) tNt POSSSIILL Rl'aF TD Tllt IILdLTII OF - NON-SStO•ran3 YROM ?ASS1Y8 SMOKING • ire smoking mearts the inhalation by othon of tobncro smoke in the aie oflctldosed.spaos .rhere pcopte are stnokino. - . gnifiant air pollution tnay occur under such mnditions ZVe mnsider th matter here, since pipe and ci, r sDlokers en produc more snmke in ' ih ir immtnlintccitinity titan cigvrcttc smoken. Ir is impattcu to knovc both th lerel of tmie substances under such cendiefons:ati .eiuther dli3 wuld , aQ* the heattlt of nan-smokets (I) TILE LEYEL OF POLLIITTOH • ' - Tn a Ccnnan study (Fiawwwrr.sol., IqG3) it+na round that cnn-smokcn '' in thickly atnoh¢-fill confaencc roatna, nstaennts or rntl.uy arria_es - -mi ht inhale three tit•o millit:ranu of nicotine in one hour, the equi.alent ' .I of t least oac eia •ex snakud. In theu crcumstartces, dse erbms-atoo- '
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:ased ptrova- '. 'iciency (aee I i::g controls i Ivnce of ab- ~ 1:1ales in the i ~I:o-thirds of .< cannot at e contribu- ~ C'OPD. aoking and ~,:6) have ' :ien and the ' in the sec- a summary :npnred the avins who , :il;its. They . < related to ; -I concluded . ,Is was sup- . ^anappre- '-iwd to the -tic and G_ .. ?urnes and pairs for - r.cmeters - -echanges .. s are out- . . :vl discus- i:creditary ~ :,~cnce of ~ ~,on (78) ,meen the capacity ;h added Is intrigu- ..utosomat ~ -iders the :•. has been : may be . -=octional en asso- ciated with a particular type of pulmonary emphysema. While the majority of lungs of emphysematous patients reveal bullous or centrilobular deformities, particularly of the upper lobes, this hereditary disorder reveals a panacinar change, most severe in the lower lobes (101, E15, SP6). Patients with emphysema who are found to have the homozygous deficiency have been observed to include a greater percentage of female patients than is usua)ly ob- served in the general emphysema popnlation. Their diseasa begins earlier, is more severe. is characterized by dyspnea rather than cough, and frequently is anasaociated with a history of preceding bronchitis (101,YZS,YY8). Radiographic studies of A,AT-deficient patients have revealed decreased vascularization of the lower lobes and increased vascalarization of the upper lobes (101, 213). It is estimated that between 1 and 2 percent of patients with COPD have this homozygous de8ciency (78, 216). In family studies, it has been found that almost all the homozygous individuals are symptomatic by the age of 40 and that those who are not usually show alterations in pulmonary function studies. Guenter, et al. (08) studied 7 per- sons with homozygous deficiency. Of the flve symptomatic individ-uals, 4 smoked and all bad abnormal timed vital capacity. Neither of the two asymptomatic individuals smoked or had this change in vital capacity. All 7, however, were noted to be hyposemic at rest ar.d to hava decreased puLmonary diffusing capacity. Itbas•.beetrdcggwted:(15S) that the lack of this proteinase in- hibitor in the serum of bomozygous patients predisposes them to . emphysema in the following manner: Leukocytea present-in the _ blood contain significant amounts of proteinase enzymes as part of the overall defense mechanism against infection t thebreekdown of thew-cd]s durlneacutrintectioa..releeses proteinasee•intc6 thepul- monaq. Siasuas.andcthewc--mithouttho-preaenceof ar normah inhib: itor.ma.YContribnttrtoWthebreakdowaof theatraetural proteinsof, lung tisaw. . . Heterozygous individuals have been defined as those who show levels of A,AT intermediate between those of normais and those with bomeapgous deficiency. At the present time, there is much debate about whether or not heterosygotes for A,AT are at a greater risk of developing COPD than are A,AT normals. A major difficulty is the Iack of a precise definition of heterozygosity. At present the best method for the determination of the level of A,AT appears to be that of crosaed serum immunoelectrapboresis be- . caaae levels of trypsin inhibitory capacity (TIC) have been shown to rise acutely with infections. ' ,. Welch, et al. (P26) feel that heterozygotes do not show an in- creased susceptibility to COPD. The heterozygotes which they studied showed symptoms of bronchitis and did not present the . -~,0020624 ~ ~.'. TIFL 0305598
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F tlitt)I.\S J. t'n.,,:r n.•. La•rh• P15.A naT' :tnd Itrltcrten>iun ;ttc ndmcir, Iht..+c uidt :t Vurtiticc hcrita>;c altd I ntulriplc Iretitivc individu:d tr;tils. Whilr uot ;tll murh (:roup I indMAuaIs Icill ' tlcvelup tlwav in tuiddtc lilv, a aubnl:wti;ll pro)natinn o'l/!. Xutr 6 t11c time to : .titrP Iltc acnml tm.rvk nf prt•vcnliun. 13p ~rltti'ting thcr xwrcptiLlc wul:jct•ta ml a' .cule st'ale antl di.'iJiuK tlhtn into Ie+t :wd t'(Attrtd grunpa• the Way is clc:tr to ' Iw~;iu the :tpprnktl nf earitnlv mt:murta t':dcttkttctl It> PtL.1IKtnc und ultitnnlclc , to preccnt thcx Jisaa.v~. ' 4 Th•nu •- Ttr•.u ' Ui.nae-In1. \lol• t:dJ9, 1957. . t.,C.I4.: Thrllvrinur•Jllqµrtrmiwt..\nt.1•\Ad.S'.~tc;rti.In3i w G It.. Il.ttrnulp '. I.., ILldl.•r¢, F:. F.. mnl 1luelhlil, 11, J: UAwnmhm. ut thr 6.)ivWn:d F:14,.L.J tintn4in/: un thr Ilin.l IYrs.urc. Hwn Kute. Stmlc \'.iaun:. uuJ \duh Wn Int \( l Ltltl71 t2Wi d H d h 1' . n . . . ~ . . r. t •nnlR . Canlute Uutrwn . Y J. .Tlu.m,v. C. It.: Ulnen'.eti•ne rm Snne Pu.,dJr 4 F::.wd,:l Il.µant.i.m and Cnr•nlan•:\nm'. Ui+vw. C, Ilyµn:h•Ja.ha.utia in ile.Jthy \','uuq .lJult•. .tn1.7. \tnl. tit'. 2•ISsR`i't. 195tx 9 In, ThunmwC.Ii.t'fl.l»: Ivl.ll-holl Slt•arariu¢ the Ki•k 4 ('•.r•,uln' Ilr.nt 1)ivstv in.Wnlt P.qu4ti.xt Gnnlln: .l SpmPv'iuut. Am. I• I'nL. Ilc:tlth IT: m•. 4 tiupplcnen6.\I•fl. 1957• IQr. ihtulnr, '1'. K.. 1La.e. F. t?., Aud .lluen• G. V.: Uw•nury Flrart INwJ.r in the FrxnLnthant Sttnlr. p. 4. i Itlh. ILrh•.1. T., Iteun• :1• S.. tlilla.m. ft. F F•~ntRl, P. F., wnd R.wne, K. F.: .\ t ~ Pmyln'Krv Stn.b- •d DrVe.ntutirr Cunli•w;wvhv tti. m:111nuv: Kepun uf Thne \'sv: Kwprriwuv-1. I.ehrntir Umet I lirar.p. !S, I lk. Chapuuu. 1. ]t_ Ocrltr. L. \, Itivwr, N'., Lnrlalnl. I/. H.. and ITillipn, t;•; The Cin'aal Sr:um d a Hq .ulate.• Gruup:+ Lw. •\nlrrlea 1'ntlar (N.»reut:nt fw '1'ttu , MKFFKEI.'4Y t. Ilitl:nan, C. C.. La•e,r. K. L.. Nnnu4 11•. t). alul ISMtr, t•. P.: Stmlia~.1 01~..1 I'rvsrnrc in .\rtpy OHittn: Olrnrnntiat. ILiv.l un an .\ICJc.i„ d Ihr tlnlnni Kn.'nb .d 11 i J l Uf6rcr: d thr I'nitn lSt.iu+ Army, I'H1: I bt 1=R 1tL9, P/Nt h'r 1YR:In!'t. 19i3. (AI I39:}yj. 1915: n•- Ia1:93t. 191n:....1 d' Ilia:7. 1917. L Kae.an'h(1r,lat!15•I•.S,I'uLlicllrillh\.ritv.\::lunullnaituhadlkvhh. .\,lmd)'u( tha• Faatur. \Chirh ]lalHo.•( \'alur In the 1'n+lirtiun:wd 1'revvntLw 4 11.pertnuive and .\ttt++••+Imair Ilv~a 1)i.-..v..•. I•nq.a.v.l u: )Lay. Itl1h: 6uuKuntnl ~nt (kY. f. 1146, .1. Thnntah C II•: Uln.•rvdlinro.rt Flmw• P-.i1Je I~m'n1..n •d Ii.,.•inial Ilvlwn. 6a. au:l Cun+ury.\rtrn' Ili-caxt Hull. fuhu~ Ilnpl:iu• ILnp1 bValV• 1951. i. TMwtctn. C. It_ aud Cdtno It. 11.: 'I'hr Fav.ilul Urr.:rmnr ut Ilrlxnrn+.umtd G~r.wun• ' •\rtrn'Ili,ax•.1CithUlnanatio.oClr.cYninvOLa±ilynn.l Ili;i6vtt:..\nu.lnl.)InL t2e+tt; 1933. S. Thnna.n C. It•: CA..rxYa•ri>liva •~f ILv Ln1i.iAnal a> GuiJ,~ry.r. w.Au Pn.uniua u( 11mn ' to Thnr i.l. ' 11. (4Jt. 1t'...Inf La+'. E. .1.: E'n"u.dc lLluc n[ U(r Ltr.r.u.rr SLrtd:n• Inrutig:ati.xr, T O0L,o ~ --------~~_.~ TIFL 0305592
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OVEOICAL WO It LD NEWS _ [d/lee', MORRIs flSNaeIM. M.a. II caw551NMt Edhe.: RCWAPD A. USR M.D. EdkMbl AlW/eq aele4 in Pr E. Am+n, Pn.O.. alaRe [. cir 1. ancllYd, M.D., Surch, M.D., MIaI1M E. I D.BIIMY M D., IUrdd 5. DIIM. M.D.,:ct~n H. AMrlq, M.D., A D, eIM.W 3. M.Mx, , ~I4. ln. ND.,WMW , Mce/lt M.C., IEM t. awree . M.D.. enrdon A. Vln . Dhbn. M,D. !yFaeeYW. EJMer•. NOWND M - Mtn,afne Cdav: JOxM P. efla AA7 :/kt,nt AMneChlC Edaa.' MALD 5. AU&a - ~-Mlkns. CGxaa: MMqi o. NPSxaq¢q, W/IL/AM 6 M R I N R 1 4 AR/N.1 [CF Y , Y EM CNRN 1 I .'AkE$ W ' RICE Spechl YroMett EdMv: 9AM l l[s$q Medree1 O/e.atuw LAVIG x, M eMEA. M.D. : AI< Dlnclan 105EPN MND[ MI«t ECINn A. x. TAMNtx ; Awca.M Mwn [diror. MM W. P,T,m I N,tb+.« CeenePendenfv b eCa R MIppn, AsleR 4. IUmE. Ia} Mlme tuel ' SWer WrrMC Alsnd D. 9 Cretm emlb Mu . . R, Wn M enM°L Nm N MA[II, eM, 4. 61n.6tn d „4eseLt. Edasr« vnu1e 4 Anmry, IuDN C. Fnn, t:.,.e 1 elyenle, nM M na, 1eMY L. PShete.n, Ma/iIMA Ru511, Doulki W. E. W P/n Mehl Weall AtMbnt edttun: M.ry V. epe , IMP. N<r4ebA MWM 6Yr.w1: MlalenP, ollsEy Y/DDOSIM (CMen, pnn M. aMmpM wn lr n Ie e n r M b mP A/ \/ r tn.W.. Ednor, Medid / a I M M i r t [AIH[a, pLY9 N, vAT Icnie ...rl/, Alrt OereimsYl evN/CUe/n[ td/l.r« 4arol ne, larcha MeLWINiA, Mlvelel D•Deneell. M.D; P/W IPr N., MM AnL S R. i yllen, Ph,O.: smld sPYtePn. E [m. 1. nyler, Icnn W ia McGnMlnr Mwn 9Yr.w.e 4MUr Meen (e~nRnr)1 hmee a, $YIIIYm tClnMl M [/r/, 1W.5I6mC tM.u Pr. Wmeetk e;lleauen teu Ieo1,A (M,MAM, Meitll Bmcue4 DensPfA: av nd LAINa: A4xa, inn<b AiAEny: 4hkIP~ Aa iP: CIPdu1L Atlnur 'E~mmemqn; Wllu. MMn P x.aMCn. Iklley Des.nan; t a L 6 'Er nMeIt LTU WHP: ,1/p IP. AALRnI MNWyr Iw M S [t A MSeu[M stew ensMN I . W `: ` P M1 e aW MM, t ,M MI,~ T I ~q RURE'M -M/le / IrMFI ~ s « M r W1 [ ' DerdI1F, IrvM8.4 lnM 9NIA , K M[aj x/tl Man.dl Ih tIMPn, lolln ahNn; c leex SOr; M//n.. n[e WN I . DenN n»., N A «: PWe AmM rMla: a .MUeauMM.LUwan.n,.e Nes re.Mn Coy Wst ChNL OLIV( A CaMld lan0 ceor [Cnarr. M31 IPL CnnY DM.6 vnn !nK Itb ubwll. . Seenly M,eins, sUrrarer 9.M5 Mym ~. uLr,rkn: AanMe )rn Mln: erlb.4 Avfuc wnllaAa EveuaY. AYlseentl: aMn 010 N[14 GM[w n,p, eqsla. Lwlq nik!~, RPMnsen, AN, Y !I bi5 I<ew, CMSeMe PuF RIORNe. M1rMP PMl1. ry N nSb ~,[dae.l,flukWtrDAflMM A.IrOMSr,IdiDlatMwq ~ An Edyln ADCeU Le'Clrer A/WatN AM DlMpes . Af4rt 9,nenPAMp T) WAy: M.Men qeEMS M ' IknnF. M.nn, SIMP r dp d~ r•oa~RD M nM Yw MqLER N o~l/u :, ~ A D . C, AS / IMbn4 LIIp. N. Slunw/ll nAWIeA UsPn FradYetNrl Af.ny,r. MI M.nyn: AMn areq f1 xECM~/1PP ry~o- YI Tn a11N+e1.N.netNMFLDI G CM A»emh md Clrtur.MOn a heyw rDNll WAT[eM r4.Alr s.M, Aeen. 1. [MDLEy MacAIAW 4.MnDPLEA.[AUOA . .. »e sP AdeDr...MI4 N leserona bMOL M. Allr„ NIMI MI R Emlrr, 1 IM n e M l fllen TuuM[, saINI Vk. YN. hntd/nli 4au N nb; er n . M P. P.esbwb: bM R G [ - R LNrerMll P.W r. Ca.V. Drsa4tlmpMl IL NON M MrnMee~turln ; JlromC D. MlnMll, KIIL4 e1Nd 4 JensMl, te, PMIYSMa rA dlel0p AdInMI Wlllen; AoWt M. INnMI1M','si,lj/lp, t OWn d~ ~ ~f Y M e lN S I I OMIr M iwG l /^.noe, NeW raS N, r. 1.0 7 I P r1 N 4 W . Ylr» trd aMeN. Idll IntlWY tr }wr N1es1 sop/ ea 1 N Nr. AIIM e» [ al Mlr a/ eN, .Ae Mf /M1tA A LETTER FROM THE PUBLISHER (3) NCTICE: THIS MATERIAL MAY BE PROTECTED 8Y COPYqtGHT LAW 1TITLE t711.S, s;ODE) E xecutive editor Howard Cohn recently addressed the annual con- vention of the American Medical Writers Associatfon. The tltle` of his talk was: "When Medicine and Journalism Meet," and in it he set forth three standards which have been MwN goals since this magazine was born nine years ago and revolutionized medical jour- nalism by introducing rsewsmagazine techniques to a periodical for physicians. I believe they bear repeating. The first goai of the',fwn reporter, said our executive editor, is to present the news in perspective. The writer must go beyond quot- ing or paraphrasing a clinical paper, He must ask questions-of the author, and of other investigators in the same area of research. When an earlier theory is contradicted, the proponent of that earlier opinion must be con- tacted for reaction and comments. The phy- sician reader is entitled to contrary opinions and honest appraisals. Failure to recognize this tenet would be a disservice to medicine. Secondly, we consider it our obligation to ferret out important stories. The "scoop" is as honorable a word to Mwu as it is to the New York Times or for CBS News. We took and take considerable pride in having previewed the results of the FDA report on the pill before public release; of getting the medical exam- ineri fust-hand, behind-the-scenes report of the autopsy squabble in lhe Kopechae-Kennedy case; of describing the dramatic English cx- periments to bring sight to the blind. In all ca]es, axclllslve reports must R.eet the goal which supersedes all others: complete reliabil- - ity. But how satisfying it also is to know that CoNn:mteewelive6y they were seen by readers in Mwu hnt-for at our magazine being first with a significant story is one of the yardsticks of success. Finally, our executive editor told the assemblage of writca, there is a tool of the trade we choose to believe cannot be ignored: the English langs:age, Medicine is a science, and complex, s<ientlfic terminology obviously must be understood and emp loyed, But clarity remains a prerequisite of communicating. We refuse to accept a veneer of pretentiousness-obtuse, involuted sentences and the over- use of multisyliabic words in place of the more easily understood ones which should have been used. 'Thtxoughness in reporting, initiative in finding and developin Ig news, ckarityandstyleinwrit'L1g-,atMEDICAlwt)RLDNEWS, wesub- I mit that these are the cornerstones when journalism meets medicine just as they muu be the standards for vibrant, responsible journalism in reporting scientific activities everywhere. TIFL 0305499 9
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; I ~ add four-I'Fancer grant A member olf the editorial boards of the publications, Archives ef Patholoav.l Diabetes, and Laboratory Znvestigation. Dr. Lacy is the autho:l of many scientific articles and chapters in leading medical t~xtbooks. 3/11/71 # # M 7'a,w0s87 TIFL 0305674
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rere •tvn Ctr•„trt sntorIxc 6st One a11tIMr,IdhMrJn• rniay im1rYl IIiR 16 rRr cent. nCa eram nCalt.'reic s.ulcnts YerC rI11Me'AIt\' pC14111t~ 1,1IIII•aecu..~••L, aml tau•:I•a r( f i{.r, i•pil tlut I; t<r a%:tt. of pati.+lq arith rv,Gdcltnry all.r.;y b>tt r,..ai\r x_in teaa ta Sn a rt+rdqtr rtlutly (]ptar. I7o.{ a ElCN• cnnry, d nnn.+nd:an \r'+t .pu-NNnud uKlw{01l' YNt1C tea tt'ere allen_ie. llu'rc wetr In+plan ownplaintf ot e.v irntuinn in Iw;h enw; a. . but u.+sal .pmluuu. mu4h and uIn'a:ut3 occurred tnaro uften in tlc all¢rs'ie yatienq. It..'as mnsillcrt.'tt that the cffect of tobacro smok: \ras irtieti.c mther, than truly allerec•nic.'('hia ecidenea eonfirms the genenl impjeasion ttnt noo- f smokers are ofu•n distrcuad by a stnwy ntmosphcre. . . Apart from the p>sxihle ht_lth huisrda, dtc nuisnna ralue of nttotdrtg in general, and pil:e and ee r smnking in partieuiar, ncedsconsidcration.So:ne non-smokers wfler considerable discom(ert in thc pr¢:ucee of smokers and this is certainly not limited to d~~rttte smoking. pipes in portiotlarctn pro- . duce objt:ctitm.ible t•n[umrx of smoke, apadally in cnrlostd spaca. \on- - stnoL•ers are often u{.set by inving to trork a!otysida stookets. In public placcs, the right to be Icec from wtoke siteiald have a higttQ priority than .. . . hinnetf a nuuanw to other psvipl.'- J. S. Atat.; :_ ' thuafarl-nniteJ;hemustnetnul•e - ' . °!vo liberty of the i»d'i\iduat.macbo . . . ~ - ~ ~ the right to smoke. moking at borne, a'hilc en.rllina, at \terh, and in plaecs of entertaintnmr, wring ttut so doirV .rill not upsct nort-sntokers who atapres¢ne'lllwn rtnal prsedee, and special arras should be set asido far those trho wish to oftc $mokets should not smokeacworkor in +aerdoyz tsithout.fiet. ln pubGm pL•rcu, tho right.to be frce fraurs smoke shoutd have a h-;her. tortty tkut the ry,•ht to stnnk~ Van-smokin, should ba mslsidercd the. . eatth is not to srnako at aLL 1'hc t•iprette unoker.cho o unable to stop, er aq not trisb.to do so, might rui!uoe the risk by chaorinq to pipa or ~i;x kingso long as lta smokp !cu tobacco and is an'fu[ not to itthakt .• - udt as eats, smnkinF on lead to a orbon-rnonosit[c leed of go p.p.m. or orcqu•hidtisaboctttheleeelpennittcdinindustry. ' Tho only aa,r in which toba.eo smol'ers san a.roid the risks to their ung disnsa •Il:c sntokc frotu pipes and cigats s at !cx as icriruinq as thu rou cisarettes In alr-eroulktt, ifI•ra.•w?ated roomx or in enclosa[ spam tttcreased tiatt of de.elop:n~ lun~ ar x a r.>r:oh teas for !oa~ snnd'rn~ ,::pe ' and;or cigar saxkers than for d, rena strwkrs aad tke lattcr may not reduce their risk if dteydtan.n to pipc or eizar sttta'.ing. -. ' ; . There is no avGkneo that oal:cr people s smoke is dangerotti to he.'tlth,v ~. non-smokcts, but it aut be estrrmdy irrit:deg and ettusa diatressing symp- onn, espeeiaUy in aller; o(wsons ot in thtsse already affeeurd by heart or - Thc smoking of pipes or rigtrs is a much kss dangerous habit tisatt the. ~stnoking of eigarv'tta• but it does ineraue t&a rat: af detZIoping wnexc of -, .. rhe mouth, throat,aesaphagtts and lung abocc that of nen-rstwkera. Tha 511dtNARY~A\D COYCZOStO\Y -
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add two--' ancer grant $1,000.00 0 0 in equipment which is applicable to the research and has acquired lan additional floor of laboratory space. Drsj. Tillack, Rosai and v.T. Marohesi, who is with the Nationallinstitutes of Health, have developed a new method for extracti the specific antigen from cancer of the colon in a highly p rified state. The antigen was originally identified by Dr. Phil ip Gold of McGill University, Montreal. The antigen is released~into the blood stream of the patient, and if the body is unsuccess~ful in producing antibodies to attempt to destroy the antigen and the cancer cells producing the antigen, the cancer of ther colo. continues to grow and spreads into other organs. One would ex.ect to find the antibody to the cancer antigen in the blood st eam when the cancer was just beginning to grow and before the pati nt had clinical or X-ray evidence of the tumor. Several laborato ies including Washington University are working to develop a blood 8eat to detect sp-cif_c, antigen-antibody response in patientslwith cancer of the colon. if a satisfactory testing techniquo~ is developed, it may be possible to screen large populati ns of people for early and curable cancer of the colon. Af er the Washington University scientists have completed their st dy of the colon anticen, they will use the information and techniqu s gained in this work to attempt to isolate specific antigenslfrom various types of cancer of the lung. If tumor- specific could be cancar_ antigens of the lung are identified, then these antigens used to try to develop blood tests to detect early lung r0 o'.7 u bb5 - more - TIFL 0305672
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Intemiu 1{I. 236-243 (1973) :fl by Spd ae-verlat 1971 (BY COPYRGHT IAWT(Tp1LE MAY U.SE Pt;ppE)~~~ Zur Frage des Einflusses von Tabakrauch auf die Morbiditat von Nichtrauchern* H. Scbievelbein [rnntm fur Klinuche CTUnie uod KlinisrM Biochemie der tlmvenltlt M¢nc5m, Abtelluna fur Praventivmedizm (VOntelmr: Prof. Dr. H. Schievelbein) I Es i t hekannt, daB statistisch-epidemiologische Korrela 'onen Zwischen dem Zigarettenrauchen und bestimm en Erkfankungen bestehen, und daB das Zigarett uchrn als Risiko(aktor bei Erkrankuogen bestim r Organsysteme erkannt worden ist. Dieae Beaeh gea betreffen Raucher (Obersichren s. °). Die erwahn n Beziehungen sind in den meisten Unter- suchun n dutch Vergleich der MorbiditAt und der Mortali -t zwlschen Rauchem und Nicbtrauchern a- arbeitet worden. Sie sagen aichts dar4ba aus, ob die passive xposition gegenuber Tabakrauch such ein er- h6hta isiko des Exponierte¢ gegenuber dem Nicht- exponi en bewirkt. Dieses Problem ist im Zuge der Diskuu on uber die Umweltverschmutzung, in diesem Fall de Luttveru¢reini8ung, aufgenucht uad wird gegen nig kbhatt dislo¢iert. Unt rsuchuagen hinslchtGch der Kodie¢tration da Wirkun der Exposition gegenuber Rauchbestandtei- len in r Atmosph3te sind lange nicht so intensiv und gut ko trolliert durchgefilhrt worden ais dkjenigea Untea hu¢gen, die sich aut das Gesundheltsdsiko des Ra chers selhst beriehe¢. Die vorliege¢de Uba- sicbt u r die vorhandene Literamr soB wie folgt ei¢- geteilt aden: 1. Di Konzentration von Tabakrauchbatandteilen in er Luft L t. Ni ti¢ 1.2. K hienmonoxid 1.3. K hlenwsaserstoffe und weitere Rauchbatand- tei e 2. ' Aufnahme von Tabak:aucbbeuandteilen in de Orgsaismus 2.1. Ni tin 2.2. K hleamonoxid 3. A ute biologiache Wirkung des Rauches und vo CO ' Diese Ubar9cht +vrde anae(artiet unter Zuhilrenettme der Publika'on: The Health Consequences of Smukina• A Repon of the uraean Gananl: 1972, U.S. Departmeut of Heah)y 8duati n, and WeBere, Publie Health Smvim I Larsa P. S., Haab EL a., Sitrette, H.: Tobacco - Fipmt- mensd dtnfe.l Studlro. Ballitssatat The Wihiams and Wi4 kiaa Cu tB61, SuppL 10611, SuppL n 1971. - Seainemein, H.: Nikutin - Phermako/opw dn Sabektautltee. SNnprt: Thieme 1968. Wyndec, E. L., Horfinemi, D.: Tobecco and Tobeso smoko. ew York-London: Acadeimc Pnaa 1967. 4. Chronische biologische Wirkung des Raucha 4.1. Arterioakkrosc 4.2. [rritation<n uad allergische Reaktionen 4.3. Periphere Durchblutungsst6rungen 5. Gesundbeinkhe Wirkung der passivea Inhalation von Zigarettenrauch im Tierexperiment 6. SchluBbemerkungen. 1. Die Konuatratioa ron TabakrsucbbestandteBm In der Lsdt Tabakrauchbesta¢dteile in der Luft stammeo aus 2 Quellen: aus dens Hauptstromrauch und aus dem Nebenstromraucb. Der Hauptstromrauch kommt aus dem MundstUckseade der Zigarette wdlsrend des Zie- hena da Rauchers, wahrend der Nebea4romrauch aus dent brenoenden Ende des Tabakproduktes und aus dem MundstGck zwiscben den Z1)gen stammt. Zum Nebensrromrauch z5hlt euch der Rauch, der durch das pordse Papier entweicht, der Diffusions- strom nach Neurath (34]. Der Tabakrauc8, der in die Atmosphgre abgegeben wird, besteht also aw dem gesamten Nebenstromrauch und aus dem Tell des Haupntromrauches, welcher eatweder in der Mund- h6ble da Rauchers oder in die Lungen eingeatmet und wieda ausgeatmet wurde. Die Konzentration an Tabakrauchbestandteilen in der Luft hangt ab von der Menge da produaerten Rauches, von der Tiefe der Inhalation durch den Raucher, von der Ventilation des betre/fende¢ Raumes, von der Retention von Rauchbesrandtei[en durch den Organismus da Rau- chers und von der Seditnentation von Rauchbestand• teilen. Wie von Dathamn u. Mitarh. (9J gezeigt werden konnte, werden beim Rauchen durch die Mundbtlhle ungef8hr 60% der wassalSsGchen, fliichtlgen Kom- ponenten (LB. Acetaldehyd), 20% der oicht wasser- Idslichen, flik.ysNgen Batandtcile (a.B. Isopren), 16%s des Kondensata und 3% da Kohlenstottmonoxids resorbierL Auf diese Weise „filten" der Raucha, der nicht inhaliut, eine¢ Teil des Raucha in seirser Mund- h6hk, bevee er sk wieder in die urnQebende Lu1l ao- gibt. Beim itlhaliaetsden Raucher retitskrt dcr Orga- nismus 86-99% der fiBOhtigen Substanun und des Konde¢sata und annihernd 54% des inhal/erten CO. n TIFL 0305613
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March 10, 1971 C O P Y Page',- 2 - are ery much aware of the rapidly materializing national goal to conquer cancer. They are mindful of the current reco endations both of the President and Leaders in Con- gres with respect to this, and at the same time they appr ciate that government funding of research, though likely to increase, will remain subject to practical limi ations. They are further impressed that the scientific team being ass led at Washington University is unsurpassed in its cap ilities to contribute to what these scientists them- se1 es foresee for the immediate future as a potentially evo ving "era of immunology of cancer." In t~his situation the University's efforts are deserving of he widest possible support. It will have the good wist~es of people everywhere for its further contributions to the well-being of man. I Sincerely, I II' Horace R. Kornegay njpi I T o0::0ss9 TIFL 0305676
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NEW~ FOR R~R W A S H I N G T 0 N U N I V E R S I T Y OFFICE OF IN RNATION U 6510 BLLBNM00 sT. Louls, rls usl alas FOR Ii~AfEDIATE RELEASE VO 5.0100, STA N 1207 Stl Louis, Mo,--A $2,000,000 grant was awarded today (3/11/71) by seven tobacco firms and a tobacco growers association to a basic research program at Washington University on the imnunologic properties of cancer, University Chancellor Thomas H. Eliot announce'i. It is the largest research grant ever made by the tobacco 'ndustry to a single institution. Ch ncellor Eliot said in making the announcement, "This unpreced nted grant by the tobacco industry makes possible a major and fund ental program in an exciting frontier of cancer research." St dies to be supported by the grant are under the direction of Dr. Lauren V. Ackerman (M.D.),-an internationally renowned authority on cancer, and Dr. Paul E. Lacy (M,D., Ph.D.), one of the world's ~eading experts on cell structure. Dr. Lacy is Edward Mallinc Irodt Professor and heads the department of pathology, Washing~on University Medical School; Dr. Ackerman is professor of patholoI I y and surgical pathology. 'l~ ~e grant was made by the R.J. Reynolds Tobacco Co., Winston- Salem, I{.C.; Brown and Williamson Tobacco Corp., Louisville, Ky.; philip rris Inc.. New York, N.Y.; Lorillard, a division of Loews Theatres I Inc.. New York, N.Y.; Liggett and Myers, Inc., New York, N.Y,p La~rus and Brother Co. Inc., Richmond, va.r United States TObacco'ICo., Greenwich, Conn. and Tobacco Associates, Inc., an organiz tion of tobacco growers, dealers and warehousemen, washing~on, D.C. -more- T0020683 PA -a00507 TIFL 0305670
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IS i1or) mnlic,v rd• I'rincetnn, in tvhieh Iru agrees life scicntists aro ovcruwed ' hy sLntistics. ~ I rcnr we hnve nll bn:o iullnenced by stntisUcnl relationships whcro if wu had obscrvntionnl tlutn wn woald discard them us not really cqeent• I (cnr l.ltat• . . . . . h.' . I Jfr. Tc.r:n,tnrr. Lrt mre nskJ•on (his quastlon: 1)o you think it would hr, ara ucunenln slnlcment to say Lhnt in mmt untlol• 5ll,henvy cioarotlu sumkem hnvu n hi„her incidcncw of heart disease thmr rtmtemolml'sl 1),•, Sou>t.vs. I xould havn to ask which men, bucauso iu n group uf fnrutets ropnrlyd by hfm'rin ((:annd. Mcll. AssoC. J., 1007, volume (1G) iE uppcureJ Lhet (heir fnrtusug prvteutall thotn.irom aty effects Utat mij;4t hurr. Iroral tluo to CiqaruttCa. .. .. .... i: -; It••..•': ;-.; 111.16 Awcriruu Indimt population it wns not proved. So I would - hmc lu Lnow tchich ~opulntion. r 1: .•:. , . ;. .- ..i iSlr. I•k:unemrr. 1\e miqhE xuy Japaocse-Anlaricnos would bu ks.s- li Ecly Imccroso of LIm stndy of 1Lrn.sluma• r 1)r. Saautans. No, sir. Tlad doesn't applyto Japanese iu Iiawnii nudonI.hcrnainlmrdofthcUnitedlitntr.s• : . .. : - :- .. .: . 'Fho.vap:utcso coronn.ry disense study by iCimnrn (Adn. Mral. Scuml. - 1967, tiuppl. 91io) simply slrowedd that smokcrb had lo~rer bloot~ ptesstux. . . .. r . , . itir. 7:cunnnrrr. titrt• bccmtr•r, wo find slwcillc nrena whoro n• r•on- I rnr•t- resnlt is discnvrred, dee•s this rnemt that wo ennnut make a stktb mcnl: wiUr tm.spccA- to Utc t{enel'nl mnlu population umbr 611 if our nnncintimt statisticnlly is as shnlr as it appears to bo {n tho Jenkins Peporlf .. , . Dr. Soatau;ns. TTn, sit• i I would not wmd, to vmko one (wcmtse I feur it would };iro nn impracs:on of cortainty where 9txtistias enn nevet' I sCiriortsly utcmt this sit-. - ..: , , . ~ , . . The Crrntvar~a. Mr. f'reyor. i1(r• 1'ur:xr•n.'Chnok you,lrfr. Cbnirrunn. 1A•. Sonuner.t, you Imve chnllcn gerl sovernl statements mntlo by other wilncwsesltcrc in a dircr,t way. Ot,o of tnY eolloagms just mcntionetl that thn hexry ptcpondernuco of tlHO eviacnea sa 1rMl'In•Ard showed ~I.bntsumkinqc:utaosdiscnsa ,.: . . t.~.. . . . A fow dnys ngo, mtothor collr.ng uC cotmnentrcl that elmnat every " -c-witm•.M1 vith tka avcnptitot ofpo.L1s _ Otte pntholnqist Il.•stifad thnt ~ n pkysicinu cordtl examtne a kmg and fcll whother the person was n (n smnker or nnt. pp IE secm.^• tat mo thnt idcn Ims he.rn tol.olly destroyed htna It srrrns (a i\i mo tJmt tonnp nf tLu thin :•s a-hicfi the geumnl public fe4ls nro trtm mtd .vhich Ilhink members of Uus commit.tca Ehonght tvmro irue, prny not, . infnct,betruo• . , ; • • . ..:. j. • , . . • 11'hnt wo a1v itrnolred in is wnighin;j the evidence, to nsorlbe n vnlun to it.. Your qunliftcnl.ions srcm to jw aLsolately impeccnirla So somn of theso mnt.ters uu which you r,lnrllcugnother.vilncc:es are impm•tmrt• Tirst, mt I hc hlnck lmag cnntroyotsy, yon stq to flatly that you cannot tell frmm it lnne tehnlhr.r n petY'nu is n wnokcr,Rr nom~nnkcr, nn4 )on challcnt/e Dr. lYillinms of Uto Amnricnn Cnncnr.Societ.y on that. Iio - `nrartsa fnr ns lo say you coukl delormino a porson's socml lifo from oxamining a Imtti. You say ynu cntPt tnll wlwthm• It is n man'or p , wommr, whrch is a drnrchnck in dclermlahrg their so:ial life. .. 1101 You say tlntly tlmt yon cmPt distingtlish bchvicen tho lung uf n smolcermnlanoustnul:crf . ~ 1)r. Sontau:nv.'Ihut is cormct I cunnot tetl Lhu diltcrcncnl hir. f'nsran. Is Llut Iltu genctnl Ieeling uf Inast palhuln~isls9 •I)r. Sututr.ns. Sir, it is nly bclinf that tho knou'IcJgo of whn.t tho, black pigmentaulavcanl.v,rnnnwly- eruinur ir•trUclev ur conl dn'l, is known to ovnry woll teniucd scrmnl-yr.uu• mcllicnj studenly nnd lhnt it , is nnt possiblo to equato hlncl<cniug of tho luug loexposuro to tobncco prodrretA'.--__.. , . 1t issimply frnm Lho ezprKwv: Lo mbnn itir in {[encnJ m, in Lho cuso of conl minur's, in tlmir n•ork they inlnrlu Lhe coal dust pm'ticlos. .. Mr. t'anxt;a. So Utaty ou Ihdly clurllwq;c Dr. }yitliains of tlw Autcri• dm Cnncer Societ.y on Lhut slnleumutt J)r. -Sotta[r.tts. Phnt in my opinion, is misiufurumtion, e:ir-fruut bukinq nt u slido of lung unna:r, thut a lAtysicimy lie didu't say a p,ttlrologisl, can tell sumethmg nccurntely nhout the sociul lifo of the patient.. ' . . Cno caunot tall nnylhing beyond tlm fact that it is n cnucm; and I Lelicvc you cau tell it is a hmumr being. 'Phnt is about ns fnr as I could go. - • ' lfr. 1'tmvt:n. You me.ntionod that tlte Snrgeon Genernl tastiGrd hcro tbat lm I,nave as an oanmpla of Um innbility to chtpliun te huu tan discnses hu experrmoutal animnls the ensn of laprosy, which ho said could not bwiulrvduccdlnexpct•imentnlanimnls. . You say that itlLns been producr.dt Dr. ..yoMRalls. Yes, sir. Dr. ]lurford, who actually works for Lhc 4ovornmmtt domooskated it somo G years aqo nnd he receivr.d a prizo frorn t1m Amcricmt Society of Clulical 1'atlrologists for this. I nm smprisctl that tho Surqcon Qemmal had not kno.vn of Ihis. kIl•. I'drsrur. (leuoasally npenkiog, is it truo Umt you call duplicnto mosE human disaar>os in r.xpcrhnoutnl mumals or nott . Dr. So.ncsuC-lYoll,sir, iE vnrien. Cortoiu hncl.orial and viral diseases emt bo duplicnted. Certain rlcgenerxtive rlisen" am be dnplicated. Ct.herdegonartd.irodisetts~nretnorodillfcnltludnplicnle,foresniuplu, tuicriosclerosis is more difficult to produca 'I•hcro atr aomna disoasen which aro, I tLink, not fomad iu nuinmis bnt mJc in hum:rn Imings. . \{r. 1'nr•nn. lYhat I wns getting lit wns how imporlaut Is itto y'ou esautple, in mrimatvt 1)r• Sorv.u:ns.'I'u mo it is vcry impnr/mtt t.hnt tcu krep I ryin~. Next mrmth Uaere am three nrtv sumktttg rnnchinec t;aing to he examiurJ und compnred. 1Vn tmtst try to do um' ut.nuust lu get nn esperimrnlnl mndnl that cnrresponds to tho conmmn type of humnn Imtl( canccr. 'Phcrn nro !mveral trnsaav fnr tbnt. Ono is that wo tvill lumc snnro udiouuago I.hcn loward bimtsvny. ilnLil you htn•o mt ndtqttntc c.xpct'i- mmttnl modcl it is ntvfully hard to Im:n out vn.riuns cmupoucnts of mi.dtro nn<1 dcrorntstrntn n dumgo in Llto rffrct. Alyo, iL is bmrd to nnnlyr.u Ihe che.misUy tknt goes nn in lhe lissnn whrra~ fhr.m iu samo dnmugc. TkaYa arO tn'e funTUn9.'f•kctC tlrCn nnnl- lror of other rensonv. . ' - 1 f no ]rmi n hmg r-nnccr modul eompmnblo to thn hmnnn in nnlmnls, t,o rnnld ull^.r thctc hnrmnno bnlnuce. We cuuld eltQr thrir nutritintL
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March 11, 1971 Dr. ~au1 E. Lacy Dr. Lauren V. Ackerman Depa tment of Pathology wash ngton University Scho 1 of Medicine 4550 Scott Avenue St. ouis, Missouri 63110 Gent}emen: The undersigned companies were very pleased to receive froml'iyou an application for support for a research program in tlhe field of cancer immunology. we understand that the purppse of the program is to isolate and characterize specLj.fic antigens of cancer and to utilize these for the earl~+ detection, treatment and possible prevention of canci¢r in man. We are advised that cancer immunology at present is one 'pf the most promising fields for basic research and it is h~ped and expected that from properly directed research in "is area it may be possible to identify specific -T 00120690 TIFL 0305677
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THE TOBACCO INSTITUTE, INC. 177E'j H STREET, NORTHWEST WASHINGTON. D, C.2O0O6 aae-e.u. R KoMwenwT C 0 P Y March 10, 1971 Thoma H. Eliot, Chancellor 'ai11i m H. Danforth, M.D., Vice Chancellor for Me ical Affairs Kenton M. King, M.D., Dean, School of Medicine Washiington University St. 'T1louis, Missouri 63110 Gent llemen: It isl my privilege to deliver to you the enclosed communica- tion, which informs you that seven manufacturers of cigarettes and n organization of tobacco growers have agreed to provide $2 million to the University to expand significantly its re- sear h program of isolation and identification of specific canc~r antigens. The qompanies, members of The Tobacco Institute, are R. J. Reynq'lds Tobacco Company, Brown & Williamson Tobacco Corpora- tion,~ Philip Morris incorporated, Lorillard, a Division of Loew's Theatres, Inc., Liggett & Myers, Inc., Larus & Broth'er Company, Inc., and United States Tobacco Company. TobaEkca Associates joins them in this agreement. This~'is the largest research grant to any single institution in t2~e 17-year history of support from tobacco sources £or inde~endent, objective, biological research, and the latest in aliong series of such commitments which are approaching the ~40 million level. In r@aching their very favorable decision with respect to yourllresearch proposal, I know that those who are participating j 002U688 TIFL 0305675
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, add one--hcancer grant Ho~ace R. Kornegay, president of the Tobacco Institute, Washingt a. D.C., and spokesman for the tobacco group said, "Professors Ackerman and Lacy are known throughout the scientific communit~ for their distinguished contributions to medical knowledge. They lea a highly talented group at Washington University that is committe to a long-range research effort which will broaden man's basic understanding of cancer."_ Clprification of the immunologie processes involved in cancer could halve important implications in the early diagnosis, treatment, and pre Intion of certain cancers, and in further studies on the basic nature of malignancy. TM~e Washington University research program, to be supported solely qly the tobacco industry grant, is aimed at finding and analyzi[~Ig specific "foreign" substances called antigens within the human ca~ncer cell which are not present in normal cells. Usually the bod responds to antigens by producing antibodies to destroy the ant gens and the cells producing them. This is known as the immune esponse. r several years the department of pathology has been prepari g for a research program in the iaomunopathology of cancer and has had senior staff members in training towards this objective. Dr. Th as Tillack will return to Washington University in April from th National Institutes of Health after a five-year training period nd will be accompanied by Dr. Juan Rosai who has been there for one year. In addition, Dr. Richard Lynch is completing two years o training in basic imnunology and iawunochemistry with Dr. He n Eisen, Chairman, Washington University's department of microbiology. The pathology department aloo haa mere thar - more - T 00;:U684 TIFL 0305671
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.:: ' . -rtb. It, 196t apJ Wo sa0, A Resenrrh. \ye a L +Llea for a TA3TL PL•RCGI'y10N IN SAfOtCGRS iesn Cosmeil ler SeientiGe and Indaslrial otateGd to Professon A- W. Slcan and aaoe orea. Wn aa.J• N nud - locJ eel 6,LerMOnI ain ' dE ri e . 6 ala4.aes. A. P. 1 J2). 1'are. ne1.7Rlt!!'0lTI _ ' Yranu.9ewatt, n. 119f6). Srtr. nw.r. J., 2, 450. C.oapee, It. bl., 11 1ffi, 1. aW Zebck, J. P. (1959). J- Geronr- 14, x EMDar.dl, A. p. d Dourm 0 It. (1931). Selren•. f13,660. Faleener 46-7). A„n. Enpcu, (LpndJ, Lt 2i1• ' pw n. L(19J2). Prw. e.a. Arnd. Se/. rrre,h.r~A• tts. ~ Polton, J, P. lt 7f). M1'lnr6soR el PhY+iWsaY. D• 377. Ssw+ds•n, Hd A. (19Sf). T1. Pba•.needfot nl OWdimn. L. S~ nd + oul. et Te nfer, 2M ed., p. 620. ASaemiltae, Nev ~~' 1L (19sa1) A 6 (Ld) r,.nn.uarn.or.. 15. 4 The Flenl Afl+dafds, n 35. Chutetull, 6ouans D. A;935). J)u.+ren Phytsalocy. 2eda„ p. 924. 1de(lrarr-Itdt Nrv Yate. Kalmnr, kl. (19f A'm• hun• Gtnet. L. 22L ?aaRWm 1t. 11. 1959). Aurr. )• r11n. Nurr., 1,280 . RieLfet t. p., ao GmpbeY, IG, }1. (1940). Amer. I• [hy+(of., $stmm4 'T.')•r. a d A!aledee, A. P. (19]s). Prae• cer. Ar~d. aq, IVmhJ. 1 7a. Satler, 1V T. ( 3D. 7eneopk al PtarnucvbeY. p- 763. Srnnbfrs, pM de~ p`ia and Landon. SWlniam.7. f193 7. .:.tt,we.-I el Plunnneelagy, tib d. p.45t. - ayuadm, Pal ody.Jn nad fcndcnM i • SAi4ISING I AND FOOD nn~,r.,gEn,~,•n ",g Y Rexdrch Dicrtrtan $ IIRUT, Ch,O. . ;Rermrcl5 Dnrser MOf4It.:,O J. PIItRLN, D.3c, Di9.LVct ' Prom are nrps dsul Groore s VART, ASD„ U.tLC.P. iysftfdn end Senlor Lecrunr aarr ol ~frrrfe/ne. Urduc.+fry of Capetown, nnr florpdpl, Copeto~n• Jarrrk A1r+K 34 F4wMalaynu /t // __ St:rnndl i y n conjunctiun wilh the queslianary a dii ,,e hislory leas tal:en by the systam of recall, payin.. par- sieutar attontion fo Ihe (nreontent of the dict dorived from common foods: 63 smoken and 62 non-smoken acre qucstioned. ' . . Fnally, the mato smeken faQ smohinS more tbnn 20 oilnroltcslday) and nomcmokcn, wtqso aSt•s mamhed, were srJened from tho ittsumnee psnoncel tested fo: rnste sensitivity. Thus sez, ago, and saeio•eeonomic . background wero matehcd se that the reriable (anor= were limited so far at pesefbk. From thc:e men, twe amcit Sroups, A and 0, caucistin0 of heavy smokcrs aad oon-smokcrs, wcre sekcted with the use of random number labip (Pisher anti Yatcs, 1957) fot a owrg dctailed diotary iavestiSatian. N'me smokcn and eight nan•smolcers formcd group snd eie.•en smot:crs and niee non-smoten group 11. rt dclailed dcxnptioa of lha d,uly diet was oblaincd, paying attenticn not only to the maite meals but nlso to snaef;f, Ibo vsrletient during the wak nnd xtek•ends, and Ihn nmlhods ased In cool:ing. The amonnts acteo wcre gauged on avermge porlions, bet it there were ebs•ious deviations these v.vro Ufcen inte aaoant. The tat eontent of various foods was obtained Crom staodard food tables (t'os aad Golborg, 1944; AfeCanee snd Niddoason, 19Ad), , . Rewu . . Snbfeetiee Tosre PrrJrrence3s-Of the 79 smvkers who completed the quastionory on thefr preferences for salty, rpieed, sour, and bland foods, 36 mid they preferred sally foods. 50 spiced rood, 24 slsowed Dreterence far tour feed tvhik 40 prefcn'aJ btsuti lood• Of iho Tt non-ssnokers, 29 prelerred salty (cod, 39 spiced, 30 sour, and 61 b!^ad food. The dilYerencos: n•era si,nificnnt for bland foo,d (P<O.OOI), but for talty and sp(ced food combined (0.1>t~0.05) the rcsult rias not qulte signiGcaat ' . . Ssmf•qrmnrrrarivc D'uMry Surpey.-Tho tatat fat assrsred from common fatty faorLs came to a mean af 577 g.)xeel• for smokers and 543 C/o•eek for oon- smokers-that is. smoken nte a sEghdy more fatsy diet than non-smakcra I3owcver, this brief history did oot ' take into account all the fat eatcn in the diet, and We results were not ti;yoi0eadt . ' tMatkdDterepgmefa detormioe whetber Ihe diRerences in In group A. smol•ers consumed 1215 g. fatJweck as Itsvasof inter t in tatto pcreeptio that taist betwan smokers and eon. compared with 1.071 g, fetJxxek for eon•smotcrs• but smol:m (Kr t Parrie and Broate•Stcp~ary 1961 ) this sns not smtisticaQy sigrilficanc (03>P>D.J). Oa • bad any bear n: oa their food prefetences. There muro datailed uomiactiao, hov:evcr, mzi'ked diBemnces is a betief I t smaken do pseftr ntore savoury raisted in Iho typ:s of fcodz Wnt conaituted Ibc ovcr:Q foads, and tha with abstineoee (rom snsaking, mroner fat intake in those two grouq••s. f)eavy smol:ers coo• foods aro Dttf rred, and this passibty nctounts tor [he sumed i;niGcandy more mcat and moro r~5s dun did subtnQssenl ia rasa in n'efgh[ Wat bar bcen reported ncn•snso: ers, bu non-rmoLrs eousunxd somewhat (Ura2ck and t937). As thc3e impcczsions are morc L•t in tho form of raf:a, sxttt& and cha:olntc. withont any I cmaI foundalion, this study xas planncd Almost the same resulrs xzre shaxa in group Q-ibat te oblaio data - ihis regard. - Is, the total fat nns 1,155 e.h'•zcY for smoterz aad 931 g.fweck for non-smokers. Similarly, heavy smokers d DIcthods Malerlnl na consumed si,niQcandy more nuat and more eggs ihea 7ho subjeet of this shrdy wtra samp(rd from two did aan•nlwke[s, bu[ tho inwke of fat from other foads soutcn-a Lro'p o[ SD srrond•)•car mcdi-a, students and i.as e~ain not cery different (ri,^,. i). a Srpup of 7 malas Snd femaln from an insucance for Iho purpm: of sntistical ¢nalysia, gtoup A and firm letmse ag s raoScd from 1 7 yeata le :0 ycart. group I) wrre eomuined and the results shoxn as a rrslly, in pfinteJ r,ucslionary the subje:n, who mcan. The dLTcrentcs bnwan smokers and noo• eonsiNCd of 7 mnokers ond 77 non•smeken, w•ero ssked smokers fo: plcat :nd eSgs x_^[c rirpi0eant for tlssa to indieaee U ir preforences for eatty, spiccd, sour, or samPtcs (0.02>Pn0.01 ar.d QOS>P>0.02 Icspaelivcly). 'bWVa tooa., ~=...pl~: or •><6 kied bei„e aiven. . No rtatintiraCy fiClL1(L9t1t dlutiCllee was S:en in lba. TI1biN 0000616 TIFL 0305580
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2. antig ne for various types of cancer. You have informed us through your proposal that a speciific antigen for cancer of the colon has been identi- fied ~y Dr. P. Gold and his co-workers in Montreal and that Dr. J. Rosai and his group £rom Washington University haveipurified this antigen using another method. we unde~stand that similar tumor-specific antigens from cancer of the lung will be searched for: that it is hoped that serological tests might be developed for screening popu7.ations; and that iaununo-therapy could be contemplated. We are aware of the facilities and equipment available at Washington University and we believe that the intel- lect~al resources that have been developed for the support of this program are superior. Therefore, the undersigned complpnies are pleased to contribute to Washington University Schol~l of Medicine, to finance the program which has been outl~'}ned for a five-year period, a total sum of $2,000,000. The contribution of each company participating will be pl~aid in quarter-annual installments of approximately equal~l amounts. Inasmuch as the contribution is to be used I 7 00:'.0691 TIFL 0305678
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• Tlitl PItACrtTto:\En ~G.}$' . ahout 5 per crnt in ci_nrct:c and ci~.v smotc (tLe conceiturion inetetcin~ . as smnkin; prncac(1s) ~ut in uwch luwcr cnnccntntion in pitic smoke. (St)ntd.r an.l I todncn, tqG7). f n ci ~arctte smokers up to t j pcr cent. of the hanun•,;lobin nuy be contbincd tt:dt arbon mono.eWc as euba~rhacmo- glolrin, the atnottnt inerta+iag with dait,v consuntptinn and iniulnrion. Levels are much Inwer in pipe.or cigar smokets who do not inhalc(Larsoo et aL, tgGt).:lurup fnuttd dut thcrc t..n a gmccr incrtas. of athctonu in the aertu of eheleuerobfcKl nbbits e:posctl to .arbon mona.idp than in eun- - trois, atnl he su~..rts that arhon munoxide is a much nwrc important ause unoken are juse as urcrely affeued as d, rctte snofttxs. . (Vineent's gin~^icids}, lltis di;casc may result in premacurt Io:s of teeth whieh is much more often found in savuers than in oon-sttmSteca. pipe , Many studies (U.S.-PuGlic I{eilth Srnice, tgGg) have shonv tbat smoken _ are more often atfecsed :by scrious inflammition and evtadatreaion of thc gums and hona supporting the tecth, and are more liable to acute infcction of thc gums (gin,;.itia), capcciallv an acuce form with ulccn " (v1),DtsLASE3 oP Ttttt TBETU AND OD]t3 tigar sma'scra wmpar.d with ugarcue smokers. - . of arterial disase than nicotine (Astrup, t97_: Astmp er eL, tgv). This is consistent with the much lotscr risk of mrornry heart disose in pipe and;or s fatr ameuny campared aith3S per ¢nt_ of cigar smokers and 6 per ~-_ tt of pipesntnkep. Ci,^ar sutol:cn aho smo&e onlp dgats or who smoke :~~ 'gara and.pfper.idtale luss thaa eigar smokcn who also mtoko dgareua - c dsarctt¢ stooketss in the Unitul IiJnytfom.atate thae thep itilulea kt.'~_; ~ mpanti.dy few pipe or Ci;ar smoken, inhale the smake:73 per cant of :- - - tokmg probably hes tn the faet thnt most dgnrettesnwlaa, but only- '• The di/ferenee benveea the dan;erom mnsequQtco of the tuo tvpes of . .: - - ~ assay rt aL, t97r). . . . , ~ .. ~ imilareoeemnatiotu of sntake ftom aguetta made of dgar tobaao, :.; ts exposed to cigarette smoke Ince a hieha mortaGty thaa rass nMOCCd te .. . Animal ttsts have shown that condensed i ipe and'cie r snudce is mor_ t,.ti`„ty to prnduce cancer when npPiied to the skin than the wrulatsatc from eigarcttc smoke (lhcies and Day, t9Gg; ftouwwng- c« 4, :ir), and, when iuhnlctl, ttu smoke from cigar tolr.teeo produces a graxr inc:csse of resistance to airflow in the bronchial tuhes ttun d:3rette smoke (Itobc7tsott st aL, tg6g), so dtc smoke is not in itsdf Icss harmful to tissuee.This is coo- firmed by the similar fisk of aneer of the mouth and thime aad of ehronic gingi%itis of pipe smokers and cignrette smokers There is alto cridcnee that . .(vn~) WitY IS PtPe Ac4D CtOAA SMOKING NOT AS OANCE0.OCS AS CtOAaETTt: S}tOKt1Ct ~ Some prees publicity has rccently been gisa totheo idaa that if peeple,-:~ aoua.agjzf,.... . . . . -~ .
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add threer-cancer grant Amore distant possibility that could arise from clarification of theseliimmunologic processes is that specific antigens could be used to timulate further antibody production in a patient in an attempt t~o destroy cancer cells. Because cancer of the colon and lung cauq e the most fatalities in the United States today, initial work in qhe Washington University research will be directed towards these twpl types of malignancy. Drl! Ackerman is a member of many leading medical organizatiQns and serv; s as this country's representative on the World Health Organiza a member ion's International Reference Center on Bone Tumors and is of the National Cancer Institute's Board of Scientific Counselo s. The author of numerous publications on cancer, he is a member o the editorial advisory committee of Atlas of Tumor Patholo and is associate editor of the journal, cancer. Last year, Dr~ Ackerman in collaboration with Dr. J.A. del Regato completed the fourth edition of their classic text, Cancer: Dia nosi . Treatment and Procmosis. Later this month, Dr. Ackerman will rec ive the Janeway Medal, the highest honor bestowed by the AmericanlRadium Society for outstanding scientific contributions. Drll. Lacy has received numerous awards from this country and abroad f~r his outstanding research on cell structure and function. He has b en chairman for nine years of Washington University's departma t of pathology, now recognized as one of the top academic patholo departments in the nation. He served first as a member and the chairman of a National Institutes of Health study panel which re~viewed research grants in the field of cancer. He presentl} is chaili}man of an NIfi study panel on ~docrinology training and o~n the National Academy of Sciences Committee on Pathology. serves I - more 7-00;;0686
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INDEX OF PRINCIPAL INVESTIGATORS Aviado, D. M., 26, 27 Barger, A, C.. 42 BeO, B..nd Rose, C- L., 63. 64, 65, 66 Bhagal, B D., 32, 44 Bing, R. 1. 33, 34, 35, 36 Chdon, l., 13, 32, 33 Cochrane, C. G., 13, 53, 54 B.~ 23Z~ Cohen, A. Cron, C. E., 28, 19. 30 Domino, E F., 43 Erickson, C. K., 50 Essman, W. B., 44, 45, 46 Fisher, E.R., 37 Friedman, 0. D., 58, 59, 60, 61, 62 Fudenberg. H. H., 52. 69 Heracowilz, H. B., 54 Homburgu, F., 19 Lauweryns,l. M., 20, 22 Jrrncr, R. A., 17, 55, 56 Leuchtenberger, C.. 17, 18 Loosli, C. G-, 21, 68 McKenlus, H., Jr., 70 Meier, H., 14, 69, 71 Mitlman, C., 66. 67 Niden, A. H.. 31 Rose. C. L., 63 Selrzer,C. C.. 62 SkinhOj, E., 39 Slotkia, T. A., 50, 51, 52 SobB, L A.. 37, 39, 39, 41 Ttavds, 1., 25, 26, 71 Wenul, D. O., 40.41 WestfNl, T. C., 40, 47. 48, 49 Whilmire, C. E., 15 m T 0020682 INDEX OF SENIOR AUTHORB Acow, D., 40 Ambiavngar, M., 33 Andets,T. It., 64 Aviado, D. M., 26 Bhagat, B., 44 Bing, R. 1., 34, 35, 36 Boa6, R-. 63 Cochtaoc. C. G., 53, 54 Cohen. A. B.. 23, 24 Cros; C. E., 28 Daks, L. G., 58 Domino, E. F.. 43 Erickson, C, K., 50 Fsstnan, W. B., 44, 45, 46 Fadali, A. M. A., 41 Fauv<l, l. M., 36 Fisher, E. R., 37 Foa, R. R., 71 Fozard, 1. L., 65 Friedm.n, G. D. 60 Garvcy. A. 3., 63 Germa, D., 52 Green, H. O-, 52 Hashimolo, H., 35 Herd, 1. A., 42 Herscowilz, H. B., 54 Homburger, F., 19 Hung, K.S., 21 Johnson, D. A., 25 Kennel, S.1., 55, 56 Kingrhury. D. T., 17 Klalsky, A. L., 61 Kouri, K. E., 15, 16 Lacku. A. G., 37, 39 IJUwcrym, J. M.. 20. 22 ltuchtenberger, C., 17, IB Lindsey, J. R., 69 Loosli, C. O., 21. 68 --Ludowieg, 1... Mallory, P. A-, 26 McKennc, H., Jr., 70 . ' Meier, H., 14, 69, 71 Mitsman, C., 66,67 Musza/a, M. G., 28, 29, 30 Niden, A. H.. 31 O'Br¢n, R. L-, 57 Pachinger. O. M., 33 Parker,l. W., 56 Russell, S. W.. 13 Rulenberg, H. L., 38 Seltaer, C. C., 59, 61. 62. 66 Sicgdaub, A. B., 62 Skinhyj, E., 39 Slolkin, T. A., 50, 51 Tra.is, l., 71 Vidic, B., 32 W atanabe. T.. 27 Waugh, N. C., 64 Wenael, D. G-, 41 Wrtsfall, T. C., 40, 47, 48, 49 Whismire, C. E., 15 Wuepper, K. D.. 53 99 TIFL 0305669 L
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_~ - :, 5~' ~rP~~ r d R~ a lr- 36 C tw J~;I r' use of-tb meuutss tiuoq¢tuut the counu,"v will :ave many livee, Some 30 000 dmeeieans ate injured b7 5re each year-12,000 dfe ead,_pa y 50,000 undergo hospita1isstton for periods rangicg from T oo;,oszo orders nd that a wholly new chapter in medical science is about to be writ ea.. The Iostitute therefore beQeves that the time is ripe to est Iisb specialized interdisciplinuy molecular pnthology centers to expl re hon our ceUuler power plants become deranged and how tnia e be avoided or corrected and to translate and apply the new lmogte de of cellsa to the diaqaosie and treatment of human diseaae . ese =ah on geeetica and hereditary disordern is malda3 ~reat strides th che discovery of genetic factors in the predisposition of peop e to fall victim to certom diseases. There is evidence now, `rJor e~ ple, that susceptibility to1 yn2 cs` r~ is inp art iahherited. 8ome p tsoat, ic wss found, react to to'S.cco smoke and other nocoaa ft urdroc boua bo producing sigoi8cantly ittcreaxd amounts of an enzpme whioh converta these substances into active, cancercauaiag torms w' others, who react by producing only minor increases of under s e o 80 Tha• 'bl • LL b h -~ revealed the esstance of three major anag, eac'alti'of which causes one of very arcent . common fipid metaboliam dijorden which together ueamat for 20 of all ecutlcotoan7 epusodee in patients the e e, are mueh lasa likely to develop lung caacar. The heredit pa tern is suFneieaUy disttoctiva to maie it possible to dieide po ation iato thres groupd of varyiag susceptibility. Work Kis fn p greaa to perfeet a simple blood test to detect these geaettc diHeren . Studis•of the famiiiaa of heart attao survivors have• s raspona e ganes may we s 6 a most .. ~-Prevslea •dnann-Ixoduringgenee,in,-Lhs dmerican po.pulatiox: There h also been notable progass in the seerch for a reliable test to detee the carrier state ia cyatse fibroais, in order to provide a reliable asia for ReaeUe scraeniag,~~e aetie counseiing and family planning..It is e,sttmaisd that two CS carriers are mated in every 400 in the United Staw. hdany such couples are unaware that th te a 25 percent risk ia eeeh pregnancy that the resultaat • ehild wil be a victmt of this serious diaeaae. The I atitute's trauma rasearch centers program is desigped to lessen th toll of death and diaabUity by improviag the e@eetiveness of care for • juzed patients in hospitals throughout thacountry. The gosls in not 4nly to develop better methods of treatmeat but to demon- strate th in practiee for the benefit of emergency medical personnel and pati ts and the Committee will expect arepost on the rolsplayed . by't6 trauma centaq in the new Emerprattey Medical System _ being de oped by the Health Services Admmtstrstion.Ia one such center, e devdopment and use of new treatment measures, has re- duced th mortaitty rate for severe burns &am 80 to 57 percent. Iy , what ma well have been an historic feat. doctors at this center wan abla tc s ve the Iife of a 9-yeaoold gir! suffering butaa over 92 percent . of her b dy. The sucew was attributed to such measures as rapid restora ' of fluids lost from the damaged tissues, early recognition end rev af of an.mis, close attention to nutrition, highly selective aaUbio ' therapx, and the application of fresh, immunologically matched cadaver sldn m~afta dttrmg anesthesia with greatly lowered blood-o tolesemblood flow and blsedin:. Adoation and routine TzFL 0305594 'i 6
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rtrE ntin ctonn s7.totcxNc 647 in ~pirit consunmptiou durin; this pcricxi. and :dcahnl is alao known to be rct ted to cmcrr uf thenwueh (I:innie ct ul., t97-)4 n t9tS, d':\rcy I'ows•r, in a reric~c uf un~cr uf thc ton`uc,;mlictcd thu the~ inercased tol-teeo eonanmptinn durinS 1l'„rSh cCar f~~~~uLd Iead to a , gce'at incrtase in dte incalence of cartcer of t::c tongue; he did not rcal•u•o cigarcun tavuld lud to much more anccr oRhe Iung mdtcr than o(the to ue. A rcvrml of arnolanG habits in fa•vur of pipes an' cigan mi;ht rct lea to his predietion pravtng correct, e•spcc.tlly if the rceerit increasc in spi ft conswuptiom mndnueam cer o( the bladder occurs about tt.ice aa often in duarette smokers ss t non-smo@en, but thcro is no evidoncc of an inaessed risk in pipe andf or 'gnasntokan(Do1LtgZ). • Ctv) GlrtoSte aso.cxtiTl7 . large prospeRire studiesindicate that the risk of dving ftom bronchitis phFscnia is'tnro or thrce'times grerterin'pipe or cigar steokers tlun in -smokcra, compared aith a tenfold itunasc in r;garettc sntokers. ]fany cs of the prnalance of productia•e cough ha.2 pro.idmf similu cen- ts in the frequancy of this symptom and hsue shosn that lung funetion. n at•eraac only sfighdy (+bout 3 per cmnf.) rcduced in pipe or eiZar ktrs cornn;nrcd n9th non-snioken, wharr.u the arerage reduction in rette smokers is of the onler of to percent (U.S. Public ffealth Servioe, ~ ~ . . - , . ' . .. } (v) conox.tar ssxnr ntsawsa 11i rshtdicsshntclitc'einerr_•edriskofrmronaryheut'diseneinthosepipe_. and cigu senokcrs who arc mainl v ti;ht sr^..okers The fw who sntae • hca •ly, or.rho inhale, run an inerosed risk, but thies ia not aslarge s tlta in •ligls ciptrctta sntoken (Ilanuaond, 196tt}. Or.e reecnt sasdy in \ew t-or;: . (Sh piro at nf., t9!xl), hoaetor, found an ina•a•ased incidence in nipeand'or '- ,. cfa k s.•nohms scnilar to drt iu modcnte cti.rcttc sraol:cs. "lptc effects ot ststottittg on the heart and biuod ressds may be due to both nic ene and earbon monoside. \~cotine. by stimulating the reiea.e d ca oiasnincs, makes thc hcart more (iable to dangerous disturbanm of its •' bea and inerema its erork.'11te rise in Woorl-fat Icvel (fae fatty aeids) is F ; _ iess ftcr pipc or cigar smokin; than after ci%•srette sroakiag, so long as the is not inhaled (ICcahbautn and BcL'Lt, x9GS). cotine in alkaiiac cigar smoke hax ba.r found to be absorbed throur,4i the (tmuth, whilst that in more acid cigaretw smoktcan cet into the blood onI hy nay of the fuao (_annitage and •furnur, tg7e). This implies dss ., ciga smokers maybe able to obtain a satisfying dose of nicotine ttithout inha ing, whilst cigarette snwkers have to inhale to get their nicodnea R t eaidencc has emphasized the role that carbon monoxide may piay •. in c usioe hart diuase in smokeo. It oceurst in mneantratioaa of up m • T 00z0szs TIFL 0305606
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1 238 H, Schievelbein: FmfluO von Tabaknueh aur die Morbidilit voa Mchtnuchern lnr.vo z<ntration etwartet man keine SchSdigung bei acha stfindiger inwlrkung. 11. Kohlenmonoxid Sreh (] beobachtete, dai3 das Rauchen von 10 Zi- garetten ' I Std bis auf einen 5 mm Smmmel in einem geschlosse enAmomit2,09mrVolumeneinCO-Niveau bis ztt 90 pm verussachen kanns. Lawther and Com- mias (30] die tnft einer ventilierten Rauchkammer arbeiteten fanden ein Niveau bis zu 20 ppm CO, nach- dem 7 Zi aretten in I Std geraucht worden waren; Spitzenwe auf dam Platz neben dam Raucher er- reichtea ppm, aBerdings aur fGr wenige Sekunden. Coburv u. Mitarb. [8] beobachteten eioe Konzentration von 20 p m CO in einem kleinen Konferenaaum, nachdem 0 Zigaretten verraucht wurden. Ia Ta elle 3 wird eine Ubersicht Uber die von der Arbeitsgc pe Harke uoter verschiedenen Versuchs- bedingua a gemessene CO-Konzentration wiederge- geben. Fa ist besonders darauf hinzuwciscst, daB diese Tabelle e' e stark vereinfaehte Zusammenstellung ist, die nur ei n Anhaltcpuakt Ober die zu arwartenden Koozen 'onen geben soll. Einzelheiten sind der Origina beit zu enmehmen. Cano . Mitarb. (71 landen bei dem bereits oben erwahate Vetsuch aach dam Rauchen von 178 Filter- agarettea ia einem 66 ms grofkn Raum 40 ppm CO. Bei eiaer nrersuchung Ober die CO-Konzentration in ame ' ' hen Verkehrsmaschinen wurde von dam National stitute for Oocupational Safety and Health eln Mittd ert von 2,8 ppm bei eiaer Gesamtzahl von 12 F(flgen mit Messung an vier verscbiedenen Steilen im Flugze g gefundea. Zur F age der MAK-Werte titr CO, s. unter 3. 13. KablensvasserstoJfe und dndere RaucRbestandteile Galus ' ova [151 fand elne Konzentration von Benc-a-py en in einem rauchigen Restaurant von 2,82 bis 14,4 g pro 100 ms, verglichen mit der AuOen- atmosph- mit 0,28-0,46mg/100m'. Hier mu0 be- 3 Diese V wmde aue fotasismen Groaden unternoo. men, ee ist re0ritanntiv tar notmale Verhilmism. achtet werden, daB das Verbrcnnea von Nabtuu~; bestandteflen zu der Gegenwart von Benz-a-" beigetragen haben konnte. Kotin und Falk (271 reigq4 da0 das Rauchkondensat dee Nebenstroms von Ziga: - retten dreimal so viel Benz-a-pyren als der Haupt,;, atrotttrauch enthalten kam. Hier mu0 jedoch auf dfe enorme Verd'unnung hingewiesen werden, die der Nebeostromrauch erfihtt. Der Tabakrauch enthilt auch Stsckoxide, besoa. den NO und NO,. Ober die Konzentration von Nos _ in rauchgef011ten RAumen ist nicbts bekannt. Es ware T~ sehr wichtig, Daten zu ermitteln, denn durah dfe R Untersuchungen von Freensaa und Haydon u. Mharb. ~, (12,13, 14, 20, 21] und von Blair u. Mitarb. (6] ist be; x kanut, da0 Nagetiece, die ]iingerc Zeit niedrigen Kon. ;" zentsationen von NOr ausgesetzt wxrden, L3sionea im BronchialepitMlundimLungenparenchymentwickela. ' Von Harke u. Mitarb. (181 wurde bei der oben et. wahnten Vermchsanordnung Acrolein und die Alde• hyde (a1s Acctaldehyd berechnet) gemessen. Acrolcin offenbar wegen seinn Reizwirkuag au} das Flimmer- epithel des Bronchialbaumes und die Aldehydtrektioa, wei( ihr eine relzende Wirkung, z.B. auf die Conjun~ tiven, zugesehrieben wird und fiir die akute Bel3stigung des Passivrauchers veraotwortlich gemacbt werden kdnnte. In eiaem 38,2 ms groBen Raum wurden nach dam Abrauchen von 30 Zigaretten in 13 min 0,46 mg Acroleln/ms und 6,5 mg AcetaldehydJms gemnsa•s, beim Verrauchen von 15, 10 und 5 Zigaretten vermin- derte sich dieser Wert auf 0,23, 0,16 und 0,07mg AcroleinJ m°. Die Werte fOr Acetaldebyd unter den- selben Bedingungen waren: 6,5, 2,9, 1,9 und 1,3 mg Acetaldehydlm'. Der MAK-Werr fur Acrolein ist 0,25 mg/m' vad fur Acetaldehyd 360 mg/ms. Harke u. Mitarb. [t8] besdmmten auch den Gebalt an Aerosol untar den erw8bnten Bedingnngea. Sie fanden nach dam Verrauchen von 30 Zigareue0 eine ma:imate Rauchkonzentration entsprechend etwa 9 mg Polystyrol Latert und nach dam Verrauchen von 5 Zi- garetten etwa I mg Polystyrol. Diese Werte sind ab Nsherungswerte aufzufassen. Vergleichbare llnter- suchungen sind nicht bekanat. Bei der oben erwahnten Messung der Kabinenluft in Verkebrsflugzeugen wurde 2. D wohl steilt dam parier decan tanch- gsner dcr f Aktit her g &ref 0 lirh n aufn:. Kohi ErgeF Es untcr sind : da8 ' 170tr ten (' relati nomr aufn; schei sich t in de Tabelle 3 VernuehN[ Tabak ce. Gramm GsbBa des Raumes (-rl) Raurhdamr (min) Belmtung (.3IStd) Maximase CO-Komeenulon in dec Raumiun Bkrt[ (ppm) akec 33 42 LBSren<n 32 57 16-t8 - 48 ( ,4 Fner: 429saatten 32 37 l6-la 408 10 102 Zipreuen• 170 120 - 28 Fllten. 102 Tigm<tlcu• 170 120 4W 9 O7,4 r 1g0Ziasralten 170 32-34 - 53 Nichtr 9 9garren ds 57 30-35 57 97Jprraa 4L 57 30-35 WB 20 Nkhu 8 Ptdka 24 57 3$-10 - 10 (33,4 r 8 Pfaifm 24 57 37-10 408 <10 • 0,9.' • 7lsuetern wuNea maohinelt abgaraucht aI5 TIFL 0305615
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3. only #or the specified project, we assume that if any part of thE funds is not needed, or cannot be usefully spent for the al~vancement of this project, that the undersigned compaq~ies will be so advised and their respective contri- butiol6s reduced proportionately, we would anticipate recei~ing periodic progress reports. It is understood that the undersigned companies are to be the sole sponsors of this project; however, you and the Washington University School of Medicine shall have sole ;control over the conduct of the project. Would you please indicate to each of the undersigned companies if you are agreeable to receiving the proposed cont~ibution for the pursuance of this research program by sign~ng and returning to each of them one of the enclosed duplj,cate copies of this letter. We wish you success in achieving the objectives of your'iproject and we feel certain that the efforts of your grou' will contribute importantly to fundamental knowledge conc rning cancer in man. (Sig}1ed BY: H H N R. J. Reynolds Tobacco Co., Winston-Salem, N.C.; 8rown and Williunson Tobacco Corp., Louisville, Ky.r Philip Morris Inc.. New York, N.Y.; Lorillard, a division of Loews Theatres Inc., New York, N.Y.; Liggett and Myers, Inc., New York, N.Y.; Larus and Brother Co. Inc., Richmond, Va.; United States Tobacco Co., Greenwich, Conn. and Tobacco Associates. Inc.)
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.•.....,.....,,.,,...:, uum,p-o,svc,u,nrcSSUre:,. lVe nnut recognixc, nlnrcovcr, llmt Ilte lobaccn intlnstry stmnds about ouo-qunrlcr of a Lilliott dullnlv n yqlr, ndrertisiug cignmttcs on tcle- vision nnd radin. . Cnt•: qu. rler n( a llillion dnl Inrv-Uutt's ahout $0 rnilliun nwra thwr tlre enliro 1968 budecl of Lhu National Camccr InstituLo. (1nc+prnrtcr uf atiil I i uu dolIurs-thnt'x nbaut tlto nmum+t hcin~r givcn Ly priraln nud plddic aaencirs to sapport eoucur resrlrclr ut the Uuilyd Slnlrs Ihisl'cur. , Qlrntly,'rt.isliula.fur/nnrc rv•Inv,linlr+ation.R'c dn nnt Imlicvo Ih:tt tia, Frdcrid Cii;+netLo LnLeliug AdvnrtLving Ad tcWdt ynu onndrd in 1965 11.19 nnrred itv tmrpu'u of prnlur.t 2 u prvt do'i hexltlt. 1Vo feel 11m1. tl+o ]uvnsmn prnlwu:d by Cont,~rcx9- tm Inhn iluts of Cnlifornia nnd Ly 93 of 6is callenguus m excdlcut: nolmnrtity, npptoronf iis In'upnail fnt' n runro 1'oRllstir,, et.rmrl;er lvnrn- iu~- stnlenwnt nn Fac:kngos mtd the inclu+ion of this trornmg in nil rig•arell.c ndvutiising; tro rndorsn tlto n•~ uiren •~ ro ln el'L• 9 erl Crf(nIV' n t):1 llges and In advm'tising, 'I'l lc A meriutn Gutcer Society is tlrmly oplwsed to legislation trhictr n•ould cslr•nd indr.fiuilcly [Improhibition against Fcalulnl m'Stntoac- tiounncignrcllendvertismg. ' L] lhn nud./cr of cnnlrolling discltso through redncinLg cigarette srnnking, tvn am coufrnntcd rrith mnll}• problcurs. The sitttatron is de- rclnping, twoplc's nttitudecs and ltkblts aro clmngiug .orj rapidly. It drux nnt svvw clmu'to ns u'hn0 tvo Inny face in tho funnn. I9lmafore, tco thinlc it impnrt+ult ttlnt you givo to tlro Nqleral Cmmnunicntio»e Cmnmit-ion Rutl the Foderul Trndo Cominaisirnt the authority to rogn- ]n/o ci(;nrette ndvcrUsing, nndar yaur supervisron and roportutg rq,ru- Inrly to Yon. 1'ht+ other day, tho Ama'Icna Cancer Society llnd R note from a U-ye:r-old girl who a•rotc: . . . I tem I n.Aerct+nd tkls, on TV nw7 I+nra a cnmmerclnl thet anyr "dau't tn,.,k+i' nod tlx•u Ilier hnrv a amnumretal that mYt ".ntvae lylvnlcu'• • \PLYdothuydnlblat • . ... 7Vu think tbat Ibis yarmg wdtcr luls n grwrl point. Our Chnlruuul of tlle 1Murd of I)in,ctols, William 13. Lowis, a tormor ndvottising execntive, said recently: - . . : tt Is m,o or Ihn daobr. urnnltcrtatlons ot the mntl tlowa in ahlclt tvo llre t6nl, nlKht nller rdqhl, nttcr u1-gl,t, on the .nurn iry HlnnuN and on tlta enmo reelo trrrour•mv, ma hrnr ovcr xna oror ornln the contrndtNorv ndrnonlllnns'Boroku. $,nnto. KnmM. Uoq't mnuke. Bnrokr, Suwke Bonko. Ilortt ®uoke,• ;, !f vrnrs to in Ilmt it is tiran ta prvxunt In brrnulcnslin;,r a mom Imiticrl rictr uf cil,ntretl.n snnnking/ oato Uurt n+llects Um anud.ry'w Inecl- iral nnd nracntilin r:alx:icncc, fn vlowul+l and listcnel:s nnd parliculndl' to )'ountj 'KOple. - ~~e Olllllf Q/nt ille rttf$StrgCY aga1119t elgntolto arnoking olt tulm'isinn ahotdd ccl'I niuly ho cout.imred ae R puhl ie sa'vuoc. They are doing a must effective and irapollud. pira•s nf edncntion--ilt fact tve tbink they nhntv very .voll thu raluo of ndvwtising. We feel Utey, m•a esszutinl nud clearly in tho public intcresf, Jlnt it is orlr strvng convietion tlrat ttm ndce.rtisiug of croarot.tcs should be stopped. . . t,+uk,.r ~ocucl iy furUtcr li. T;rowa unt oi luy dca.p pen:unnl canvirl inr~ ~ aud tho capcricncn of somo 80 yaaua a§ n CAdlolo;livl.. 1tndiotu~,risfs xr,. nhnost afl lung canccr pn16:.1t9 b',tt nnfotfllnntely tou niulcy lon I+ttc. As yon iaron-, only about 30 pcrccnt nf thn luufr cnnr.oa~ cnsry ntn tn,lny dingttu:rd whon (hey nre olurabic, 1'hu distmso In nvcll nn insnns om•. nndspra+dssornpicI ty. ' I I hnlvoludly hnvu nlalmd 00 pptiralFs ceclt ycnt' n•ilj, lon;. rnnrc+', nud it is n dlsl+ent-telt husiness, CJIO ulure sn siure thoir ilhtrs,; i; usuoIly thu rn;ult of c1gurefio smoi n hnLN. (hnt is so widr.ly nrlrn- cnled on tclhrlAlnn. 11: 1$ SmIfIelrlllM1 to nnllle In/rnc frorn a day nt (hr. Lnspi/nl in ichicL I Itnvo siuund in tlto nlfntts to s+wo a lifo frnm lun:; cancor rvith n cohnlt homh nntl to sit I+:(nrn my Iclevlziou andllror nf•rnp,clmen+inf; invilxtion tnnmakoucigmrlle. 1'l+o tray h, a,ubot Itnrg cnursr is Id,rongh prr.vcul.inn and ILa ruad to inovcnlion is throtlgh rtvoidour:u of nir'etlo sruolainp" , tVn r1n not Im.lroro thn.t Lhe end uf ei(;ntrollq Rdvnrt/sin witl u•. ei,rnretl. ' v )erlrlln,Or5le11i11itqtCJnlalelln o laaiuvo it is trmo for nl l a f u9 in lho Un iFed Sl+rlav, mrd pnrticlJn rly thoso in tlto lobnrro industry, to recomliut olu' rrsprrunrLilil.g in ndvcr- tising a ptndnck thnt causes so mu~ husfritxlixnfiun, disrdritity-, nnd prenurtuln drnth. , Thnnkyouvcrymuch. 'a. . " .. 1'hoCnnrn.rntr.Tlrnntcyou~r.I3atcor• ' Dr. lVillimns, if you wotlfd non prnrcrd nnd thut wo tvill Jmvv quostions. . , STATEMEETUF DIt. ASlIEEL 0. WILLIAfifS Dr. lirn.r.lnrls. Thnntc you, 3Sr• C9lninnmt. -I nln ARlrbcl C.1Villinms, a snr con Sroln Jnclwunvilla, Fht, n ditlln- mn#e of Eho Amm~icntt Iionrcl of~argcry nud rucrnhur of Lho Cnnccr Comnizion of tlw Amorienn Collegu of Surgcots, nnd I spenk tndny on behalf of tho Anrcrican Cancer Society irtroso ptrsidcnt I was m 1U07• L'or mlmy yPara, I lLnvo opetxtcrl nn Jrntiott9 for cmlelr, includiu" cencer of tho lung. Iatng cancer is tunque; it is a disenso in trhicli / a physicinn nced mclrJy Ionk nt Lho living lung tirsno uudnrr n micro- scopo, niUwut noy Iwotvletlgo of Ula nnticut'slusttn'y and ho cau tull , yo6 m sonm dcl~til about Uln pntlent'e socinl lifc. In olt prnhnhility the patient slnokctl eigamttes for at least 20 ycars and inhaled dceply-- ' and his wnsnmptmn nas prnhably k pack n day or nmro, . In Iimaimt roulrlfc, yon tmt onn Imllct In a t'orolrtn• nnd Ienrn frrn cbnntln+rs nnl1tty,'J'ho ndds nrn nnn in sia Umt ymr ndll Io.m ymrr lifn on tlro 6tst cltot- But with cil,mrcttus Ilia ndrls nro fnr trol':st•--if not fnr denth nt least for ln>'rr ltcidttl. 1lvury tegutnr c;;dreW, smnLrr drmtnf,a•s himsclf, fhouglr not in fho samo degnco.n Smnko cnongh cif,n- Ictlc-s, Inng cuuugh, nnd you will nhnost corlnitdy rlisnbin or dcslroy yonrsc•tt pronmtlircly by enneor, emllhysrmn, or lunrt nnd vnsctdnr diseaso, or peritnpa ulcas of tho stonlnch or duodcnuu,. Ifut ercry . r]rn yanq n. C.. Naw YT•Idenrn pv llp YRM4 or abellnp ArrLlrn or Lvrlranwmlpl nrnnk, Nuv.,nhrr 100% p0. 0n-0n. ~ T Up1!US I r;' 7 ~ r f .TIFL 0305488
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2.2.2...tobaccha industry grant including lungj cancer. An expanded program in the early detection and treatment of all types af malignant disease is also planned. The tobaqco companies selected the UCLA School of Medicine because of its strong researdh programe in host defense methanisms and malignant disease. Dr. Cline, principal investigator of the research project, was recently named Bowyer Orofessor of Medical Oncology at UCLA. Previously, he was professor of medicine al the University of California, San Prancisco.Dr. Cline will work with a distin#uished team of nationally recognized medical scientists, which he has assembled at YCLA. -UCLA. 7 00Zo6s7 TIFL 0305684
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othcr feod f.ts-sbat with I,929 The , miUt, aad cambVOOd rvmaie.s almost eoostant for food consumptton as a whole btu trheo om paya 7mDtoss d non-smotcri Cereals ara also catcn ia attention to iudivHnal feod ttams. It wm Beceusa of elmost tbe snme qaaudties by these two troups- hicat this that the anat5sls of fat intake from the diQerent rood aod eYg, hich arn savetery foods and are often cooked ilems ,ws reprued fo a aceoad rnadom sampte (Oroup vritb additi rtsl faL are prrferred by the smoker, xheseaf B)- tba rnuits af sshkh confemsed the findiogs in 8toup sweet foo am preferred by the aoe•smokor (Fit. 2). A--nansaty, that a sianifecant diQoreow exius benveco _____-_ __._ ._.. __.___._ ...._ .~_._ .. .............._ mo,'.(.e . a tmn nraees.nd..,... • , . Q,ear•sroaer. fo rnntrolfed fcedirtB aludica (Uroote-5tcenrt a ot., 1950 it tvns shoo•n that maat utd ep6s elevate the seram cholesterol levels mata rapidly aad to a greaser eatcot FI ..1~ 'r'reT thaa most othartau. . . G . b' at i so1 Pdsrt7siy fbb eeubl scc6unt for the d(6crences in sentns cholesterol lasds tbat have bcen reposmd in soneys od smokers amt aoa-mnkers (Gofnc.n er nl., 1955; ?homas, 1333 ; 1Cnrvaoen et aL. 1959/ Hrante. Sscwarr,1961} - • - . . ' Summm : . y . e rur =""C"M ruts o"ao,o21 ~a 71ts 156 iadividuafs who u'ete subJected to the laniqs Pso. 1.-~ro fot Iemke apreesd a peromna0s Wkina ~~0 9uasssioocd about their food pr.fereescas. ooasmete u 10Y6 in .sen eae), mqae~ne tanmsraa.c resuw L Whether they preferred salty, spiccd. saue, or bland rre0 Afedtleaabia tbadYlMmf00d eraaeL Innd_ rr .un e1.- r4.r ... .. ..4., ..L....A wr..A SMOi:ING AND FOOD PRCFfiRENCES ¢roups, nor in the diRerence belweco tu1a1 Ihe 1955 survey bs,ehe earne asoa (UronreStcwart, i956). , 1.176 Q. fitlureek tor smokers eompared Hourover,thedU[ereneesinfondpreferexos,particuWrly fat(vreekforneo-unokers(0.1>P>0•05Jr a9th rog.srd to fatty foods betrveen smekers and non- eMge of fut derlved froM ahcrae, butter, smoken, is eceu to bast advantage not wMm one t•vl•es food, and a fairly ti Oh proportion of smoiaas profctrcd salty and spiced foed. 2, lo additioa, the fat content of their d:et was analysed, aad it was shown that smows wosamcd saore tat than nan-smokets, but the d6tareac.x -:rc ama8. . 3. On rifore dalalled ewminatiom marked daRercnces exirted to the types of fooda that eaosdtuted the overall fat intake in two iadependeat Lroups. Hvaoy lnokcrs wotumad, si0nifecamiy moro meat and e;,~s than did „.... s'y non•smokers Nort•smnkecs eoesumed morn fnt in the ® translation . . farm, of cakea, awects, aad ebaealatq. It aas conrJuded that in these samplea dparette mr.dirmroafeD of wetlcb dlmry 6e. J} ~amtre [makina e~eeted food preferenees rar to sm toae et aeeken eee.aered .m noe- " Ne ro,rs d yavearr Ws. Nae da-menu:m rasen 7bese studm were simpoeted In put bY rneatcb prsnts faedtitsberaWt0lthdrmrmukara. aMttmSoutbAfdanCnanra'Ifor$sieotiBeaadloda:uiai f1llteaifeII . X=CU'Cb' ' . Baalr~Leas Hy the ~ oaluto, dielaty FWays cannot prOVide Droola5teofir 0.(t9$0L drh. wrd. 1.,; W9. , absolute lues. aadwQh regard to food preferences -'"f1161x, sbm.e 5~9. aae has rely o¢ sab/eeHw infotmation. For this .-~j awn, M bala. J.. aae 8rocp 7. p. p9fd1. Lare, t. reasaD, fer as ,sN possible, tdo information was N~,k 7., and Kers~ h(195'(~ Sdenee.125, 1d01. toUsatad blindly ia tbot the Indlv(dwl recording 160 p1ei'ja''AUtA w'T~d ~~ 1f9~~ Ruertxl. 4p ed.~ D• p16. dletory, ,was tlnawarft whether a emoktt oe f aon- O1,v en~9oyd, CJinem£ls nM LonJeaa sntpkq, 6cf danld. W. sed GrWker• L(1 14~ Sonu~ A/rl.mr Paod Tcara: ~ q~ Clruekd ConDne!Se. cnd Ylmnde Can:enr ol Caamon T7a biem was tackled osina three diQerent " SewA dlrlmn }•oer~staG>!. . S. Afr. Ime Med. ars, approae FIrsLLY. tha subicets indicaied their G,rn°n,-oi,cs~.rlint{neo,P. T svisawvr. n" DrL,m: 0, . Gwfm~r,. to. H9. 9roferM foreenain foods with distinctive rsstot, Next P., nao j:c.^a4 A•~t955) ,M^'a"'a• Irt, Orma, , lCeys, A., f•ieaan, P., oad teolck S. as a.tseb ent of the tat intake ftom the nlon common L- foods in heir daiy diet was nudc,' Fimlt , tao (195s), r..:r.v >. <91 Y Y sCparala l:rvq L H. rarln, e.:nvca, 1„ and nranm-Starmrq a. (t961). riadotll mplCs. drawn on two Separnte ect9aions, N'e!e subjeet to a detesled dietary analys•u. McCaeee, R: A~y aN t'.iddseson. C AL (1976). Spee. Rep. Ser. eLanrJ. nnd. Rrr. : m0 Ilaeh proaeb direats ono s attentioo to dilFeraners ia Th~ G 0.(l9Sl. J. daex. Afs. t, 198. foed pt femneoa bmezea smokcrs end naa•smukers. A txv British Stzndxrd (hS. 3214: 1:60) eihieh de:critxs '1Lo te: ts indicate that smo!ets an the ammCC saek • iho mcihod for la6ontury cvaluuiun cf didnfe.taet xtivir( 8e1nntn tuisfaetien in eonsum:nC foods that have had: at qumaincry mum.wium Wm,7unods by suspmsfoo tut nnir aa. ura nd [yfat,bilhY eeheeedd bY slMetl. hcrhs.yru«3u- :a ne ~..^JL 61e, nnd eepiee ieaY Be eblfined vinegar, olWunanl0, aod.tat. The dlRcmrnes in total Pmm tleo Od:Ide.Sta:•d.rC. hm6todeo,S.lor Deseeh, 2 Patk fat inC , a1s4a1Ch not traat, were consistent and of Sv:eL Condun \Y,1. lt msts 6s., and PonaCO W extn to 1he sa order in each inssanca This oas ako seea in - aon•mbu:ibcm. : r~,h .f&;r, rN ora . ' . . J 4 TIFL 0305581 -
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2.2.2...tobaccP industry grant including lungjcancer. An expanded program in the early detection and treatment of all typea o'f malignant disease is also planned. The tobaclKo companies selected the UCIa1 School of Medicine because of its strong researcM programs in host defense meehanisms and malignant disease. Dr. Cline, principal investigator of the research project, was recently named Bowyer Professor of Medical Oncology at UCLA. Previously, he-was professor of medicine a~ the University of California, San Francisco. Dr. Cline will work with a diatinguished team of nationally recognized medical scientists, which he has assembled at IJCLA. -U6LA- 7 002069"y TIFL 0305684
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Introduction CUNTBNTR 5 Canccr-Rc1aIM Slndics . . . - . - ~ ~ - . 7 AbslGrcts nf Reports . . . . - - ~ - ~ - 13 Canccr-Rclntcd SmJics . . . . ~ ~ • 13 The Respiratory System . . . . . ~ 20 Hcars and Circulalion . . . . ~ ~ ~ 33 i l h h 43 u ogy np ys Ncuropharmacoingy aud Pryc Pharmacology . . . . . . . . . 47 Immunobgy and Adaptivc Mechanisms . 52 Epidemiology . . . . . . . . . . 58 M-rsccllancou.s . . . . . . . . 69 Activc Projects 72 Completed Projccts . . . . ~ - ~ ~ ~ 79 Index uf Senior Aulhors . . , . . . ~ ~ 88 lssdcx of Principal Aulhms . . 89 '1'he invesrigarions supporl«I by The Comcll for l'olmeco Rcsenrch - U.S.A.. rnc. that •vcrc pnMished during 1974 arc wmmnrircd in rhis Annn:d Keporl unJer rheir xpecilie Iirloe T1mse invesliganuna rcl.lc la.gcly tn 4udier of ciparcltc smoking :md snsnk derivativcs ,od pmblcros ur Imallh. They havc been greuprd inlo enlc(prti[5 Ihnl are oriented towdrJ either SpCCilic difCasfs or organs, or that are discipline.asssnciMed, ie., .-piduminloyical, immrmological, or psycho- or ncrm+(ihannacologival. The hcallh-rclaled disturhances ne+ncialed with cigarclte smoking are also ngc-assuciated mnnilcGaliuns that nflen rc4nire prolonged pcrinds of nh<crvation in intact animalsl Iherc/orc, i, rinu crllulxr studies and cven sluJics wilh microhiul mukls have bcrn umlcrtaken. Man is the only animal that smokes for his own satisfacrion. Hcncc- ssuJ- irs are continuing on why man snsokea and those Ji.sn>xs to vhich he is sub. jeel and whieh may be associated with smoking hehavinr. Such nl..serr:qinns supply inferences or associaliom hut fail to densonslrate causes or mechamems. Animal models musl M: tucd for such experimentation. Animal models for Ihe slrwly of the problcros relating to tobacco smoking and heeilh are not easy to devise. Smoke exposurc 4s stres.ful for nnlmals and presumably prolonged perioda of smoke exposure will hc requircd. Extensive seWics bave been undertaken during 1974 to determine the nwrt satislaclory animal nmdel for smoke inhulalion sludics. Mice have been chosen hecause theyhave bcen inbred and selected lor differences in response to stress, sns- ceptibililies to diRcrent diseases, and diRerences in hislocompalahgdy and anlig<nie characleristics. Mice of diBerent inbred straim diRcr in the capacilies of Iheir liver microsonses to increase the levels of enzymes that nselnlwli>e a carcinogenic hydrocarbon, 3-methylchulanlhrene, following Ihe injection of inducing agenls. Thc+e enzymes, aryl hydmcarbon hydroxylases (AHlis). are inducible in mice of some strains so that cancer may be expressed while not expressed in mice of other strains. These enzymes arc under genetic control. The availabilily of mice of inbred strains provklex much genetic control for the animal model. The interaelion of environmental variables on essenlialty identical genotypes also can be studied. The human counlerparls to mice of inbred strains nre provided by idcnti- cal twins. The Swedish Twin Registry, which Iras provided dala on the smoking hlstories snd the ineidenco of pulmonary and vascular disensc symptnnrv in monorygutic and likc-sexed twins born in Sweden 1wlween 1986 and 1925, has been expanded 1o include nimilar data on twins born between 1925 aand 1959. This wiR provide additional dala on x population that has a long life expect- s(arted in Finland where Ihe reported incidence of lung cancer is about five times greater than that in Sweden. This should augmenl grndy the nnmbcn of identical and nomidcntical likesexed swins that .rc discordant for snsoking esperknce and other environmental expnsures. Furlhernmre, the twins among those receiving midsiphasic health dca'kups in the Northcrn Calaornia Kaiser Permanemc Medical Care Program am being surveyed as a potential source at identical and likec.mxed non-ideniknl twins that have rnlher extensive nsedi- cal and health histories and are from different racial grunpa. Significant diQcr- ences have nlready been reported in Ihe pulmonary function lexls of repre- 5 TIFL 0305627
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3 iiachool days, Dr. Huber has been interested in pulmonary diseases. Since his medical! After undergradualFe training at Washington State University, Dr. Huber received his M.D. degree in 1966 and the H.S. degree in electron microscopy in 1970 from the University of Washington School! of Medicine in Seattle. Presently, he is Chief of the Division of Respiratory DiseaFes, Thorndike ttemorial Laboratory and Harvard Medical Unit, and Director of the R'pspiratory Diseases Clinic, Department of Health and Hospitals at the Boston City Hospital. Dr. Huber is a member of the Pulmonary Diseases Advisory Committee of the National Hi eart and Lung Institute and a member of the Cardiopulmonary Council of the American Hear~ Association. He is also a member of the Board of Trustees of the Tuberculosis and ltespiratoty Disease Association in Boston. D.r. Ruber served his internship and re',aidency in nedicine on the Harvard Medical Services at the Boston City Hospital. T~n the two year period of 1968 to 1970, Dr. Huber was a research fellow in the DepartmenC, of Physiology, Harvard School of PuLlic. Health, and a research associate in the Departmenc of Health, EducaLiun and w=::ara's A.__ Po'7::tion Control Administration iz} Cincinnati, Ohio and Durham, North Carolina. During these years he investigated the':role of certain environmental pollutants on pulmoary structure and function and the~l~capac y of the lung to clear a bacterial challeu,e. Dr. Huber #sa native of Spokane, Washington, where he was botr: on January 30, 1939. Among hislprofessional memberships he lists the American Pederaalon for Clinical Research, the American Soeiety for Microbiology, the American Thoracic Siciety, the American Physiologic Sodiety, the American College of Physicians, the An•erican College of Chest Physicians and several other organizations. The Huber fpome is now in Milton, Massachusetts. (end) ," iJ0'..'0695 TIFL 0305682 ._
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2 causal relation hip for any of these or other envirormental factors has not been clearly demonstrated, bur proposal will provide a research program relative to tobacco and health, one of whose goals is to provide contributions of significant data-.to help resolve sose of! the questions that now exist concerning the effects of cigarette amoking. In adI dition, studies on differences in host susceptibility and the effect of otber.enviroPmental influences on the lung will be undertaken." . Dr. EpateI In noted that "though cigarette sacking may, and is thought by many to be, a major cau~e of lung cancer, emphysema, and chronic bronchitis, many other factors may be equally or more important in the pathogenesis of these diseases." "There arl6 nearly six hundred billion cigarettes sold in this country per year," said Dr. Huber.ili "That represents over four thousand cigarettes per year for every adult member of our p~ppulatiea. No one knows how many people in this country smoke. Estimates oa tl.n prrcental,ge oi auuiCS who smoke xuu from to aiaty per :ent. With tha= many people smoking,he emphasized, "it is of the utmost importance that any question relative to tob'aeco and health be clarified beyond any question of doubt. This contro- versy must be Y,esolved." , Speaking bn behalf of the donors, Mr. Alexander H. Galloway, chairman of the Executive Commi~lttee for the tobacco companies, said fhat Harvard is the logical institutio in which to con ytinue what he called "the insistence of the tobacco industry to help find answers to mae~ questions about smoking and health." "The Cha/q~aing Laboratory at the Boston City Hospital," said Dr. Kasa, "has a long and outatandingj~ history of interest in the influence of environmental factors and therapeutic agqnts on the defense mechanism of the host. It I well equipped for a malti-disciplidled and comprehensive approach to this complex problem." The reso~{Irces of the Harvard Medical Unit at the Boston City Hospital, the Mallory Institute of Ya'Ithology and the Thorndike Memorial Laboratory also will be available to the project inv~eatigatora, as vill the scientific knowhow or neighboring inscitutlons. (more) T 00;;-0694 TIFL 0305681-
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Bso. ' . .. TI1L• PRACTITIO:fER oxidc Icccf iu the oir could unrJ 5o Pans par nt{I(inn, the!n.Leinuun fcr- rnittcd tcrcl at uvrk. lu a fur:!a•r xwdc, in (lambur-, (lfar1cr dtKailcd incrstiT.niuni of cubon-monosidc Icvcls in die atmuydtct4 and in tt:c blonsl of pcrwns cNposcd to cnrting contcurrntions of snwkc in tftcoirs - n•crcnrrialout. In 3 rmm m.merin2 ahout ro x ts !'ert (7 x s•s metreA. ss dennttes tteea smo!ccd in t6 to tl m6mws aitiuwt vmmlu:nn. CO emut•ntnd-ns uf y5 to gs p.aatr r ind niCetinu IXVteRltmti~wn of ey0 to O'54 m'1.;'nlt'it mctN WtYS r.T'lLeVl. \\ ith venrilariaL s!uw !••a•ta fdl rnrilly- 'lUt• rnokina: of niue eivn en 7e en Ii rnenuto toused carbon-monwrida !¢ra!s of 55 to 60 p.p.m. and nicaslne le.'a{a nf rro5 .n•ij ' cubic mctra 1Trt snwke fnm+ eic!tt to nine pipes of rofaeea ouscJ rathrr laaxr -' . inhaGng one eigaretce (Ruucll et el., t97-'). ' eorbon-monaNidc let•cls could be ruised to go p.p.ru in an enedoscd ar after the smoking of taa cigaretta: theCOl-lb in tN: blood of nan-smokers ttould,.' (inrsatse (rom a per c¢nt to g pa eunt. It has atw been founi (Lautf.cr and - Coromins, 1970) tlut o•hcn sm•cn cigarettra mrre smokad in an endoud -aparx, rarbonAnonoaide leeels reached so p.p.m.. but thr:re teere tnnaimt =' peaks of go p.p.m. in the sir inhaled by a parsot sitting ttca to tbe smo'ua -.' The increase of COl•Ib in non-stnni:ets in just over aao hour in stuht condidont has becn found to be simt7ar to dxit cauacd by ssookiall; mrd+ smokers cccept under unusuaitv atnoly conditions tvittwuc vtvtffation, such r/ as those found in the erparimcnti. Another acchur (Stcit, tyrr) found that ` tltu. wMunaY: COI36 uf non-araL•cn tme kom o•q ro s< prt csnt utst 1erela of tint of snsoken from ]•3 to T3 Pur eene . . ' , . It wu concludetl thnt passive smoking ttns nota signifiemc haard to non- u CAV 4ASSI\ C S>I06I$Q At1SCT THF. -" mrottary.heart disc•aso may w(Feradvcne he:Ilth clteea. . ,- . or a dosad car, but patients skretdy suffering (rotn chronic bronnhitis ot apart from e.ceeptional etpmure to tobaceu smoke in an uncaaiLted room .. , evidcnoe Indiata that there is virtuaily no risk to the bdthy non-srnokes 'f. rcccnt United States rcport (t,.r.S. PubGeil~tt.4 Scnim tq7a).1hc presmt.:- ing the eRectof passire.smnking on healthy people ia %vil reticurd in s- (A) ecs tr aL, Sq7o). The variation in the rtsuas of dilknst triuis inmtigso-': . coronary heart disatse ivere expos¢d to 5a to soo p.p.m. of arbon monoxidq evidence u•n found suggesting a rcducion of oxygen to the Itrart muscle_' bcart unable to ftnd any impninnent of functinn in nortnal pcopic aposcd co :bett.ean go znd sSo p.p.m, of earben saonoxide. \Chm paticnes uidt - Atthough sonte uwr':crs have four•.d atidrnwt thut che 1--veLsaf etriwn mon-1-. ot;idc which mrf be found in smake-tilhd rooms may be hu5oful, others lum• ~ " `'. REALT%OFYOx-SStOI'ZRSl.-~-' -~ . . . ' ' (rP) DIEC01tFORT'TO aOK-SUOClIIS' -' toms on exposure to tobactum snwlce'. . ':;;..~ • .. . ..-... . hcace tho d=and foc non-smokina rompatmcat>'; Sruno deveJap sl7ap- : , Rtany nortamoL•cra.tlis[ifte uor@ing,.or traa•ett.ing inm smoly atmospherv:.::• 16
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240 Ta Hw schisrelbJn: Elnrlub oa Tabakna<h auf die Morbidii3t oon Nkhtnuchem l,vrry~ Ik S. COHbGehalt dea Slutn bai Rauehem und Nchlrauchem (Raunyt6lb 170 ma). (Nen\ Harae (171) COIm Raum (Dpm) 2ipnttan (InrBwmt vernuchq COfluns (0(Peton und Std) Var dem Ruxhen (COHb-'%) Nach dem Reuchm (COHb-%) Zuerdnurrs 30 103 - 3,4 7.! 11 Rwcha - 0,9 2,1 7 Nkbtramisr 3 107 16,1 3,3 5,8 11 Raucea 16,7 09 1,3 7 Nkhaaucher <5 101 33.4 27 5.0 ll Rau<ha 33,4 l,] 1.6 7 Mchuaucher i{. Hei der ercits mehrfach erwghntea Uatersucbuag vonHarke rdendieinTabe11e5aulgefuhRenCOHb- Werte getu dea. Ans der Tabelle ist ersichtlich, daB der COHb Spiegel wie erwartet bel Rauchern uoter starken Ta ucheinfluB sehr stark erbdht ist, daB jedech bei en passiven Ranchern der COHb-Spiegei auch un diesan extremea Bedingungen uur cia Niveau err bht wird, das nicht i3ber dem liegt, das durch die Exposition gegenuber der Pollution der Atmospha dutch z.B. Autoabgase erreicht wird (s. den Bei g„Lange" ditus Heftes). Nach 1 ntersuchungen von Stewart [41] wurden Probandeu die nicht raucbten, einer CO-P.oazentra- Uon von ppm ausgesetzt. Nach 15 Std erreichten die Proban en einen COHrSpiegel vou 7-8 %, auch nach Iinge Exposition (bis zu 24 Std) erb6bte sich dieser Wer nicbt, ein Gleichgewicht batte sieh offen- bar einges Ilt Nach eiaet 3stundigen Expositiou fiel der COH Wert innerhaib von 2 Std nur von 3,7 auf 2,7%. 3.Akote biologisehe Wirkmg ies Bauehsf smd von CO Nach uquette u. Mitarb. (31j soll eiae rauchende Umgebua einen Eiatlu0 auf die Herzfrequenz, dea systolische uad diastolischen Blutdruck bei Kindern im Grund hulalter ausubea'. Harke d Blaichert [191 zeigen, da0 sich EKG, Blntdtuek, Pulsfrequenz uad Hauarmperatur beim passiveo aucben nicht ver6ndern, sclbst untcr Be- dingun bei denen as den Autoren fur die Proban- den katuo och zumutbar ~erscbien, sioh in dem tauch- getOBteu um aafzubaltea. Wit in dem Abachnitt I dargelegt wurde, wird drr btAK•We fOr CO (5oppm) beim Abrauchen ~on Zigaretten nur unter Bedingungen mit extrem bohen Rauchko ntrationen erreicht Es liegen jedoch Ar- beiten ia er Literatur vor, in denen Ober Beeiatr3ch- tiguag b immter physiologiscbu Funktionen bci die- sea uad licben CO-Konenttatiouen berichtet wird. Aus diea Grunde mu6 hier aut diese Untersuchum gen ein n werdea, da es leicht vorkommen katm, d sich die Abscheidung von CO aus Tabak- rauch aus anderen Quellen addierea. 5 pu Ortalu.l dleaer Arbrit,ne aicht erreld5ar, a las nur an unvoQalindiga RCent ror. Bei den masten der Uatersuchuegea wurden Z,' positionea gegenBber CO-Koozentratiooen zwischn 50 und 100 ppm durchgefOhrt Beud vad Grandvtatt [5] beobachteten, daB die Expositionen gegeniibe 50 ppm fur 27-90 min das Htkvermdgen uad die Sebsch3Ae beeintrfichtigt und die FSbigkeit, relativei Helligkeit zu uaterscheiden. McFarland (32] beohacy-~- tetcq daB COHb-Konuntredonea von 4-5% die . Wahrnebmubg optischer Schwellenwerte becintrdch- ~ tigt. Ray und Rockwe8 (35j, die uber das Fahrverhal-* ten von 3 Personen unter verschiedenen CO-Konzen- trationen berichten, beobachteten, de610% COHb mit einer verl3ngerten Reaktionszeit fur das Beobechten von SchluOEchtern und erbbhter Unf3higkeit, die Eat- ternang zu schitsea, einhergeht. Sehulte (37] beobach- tete eine Zunahtoe der Fehlerquote bei psychischen Testverfahren sehon bef einem Niveau von 3% COHb. Es ist jedoch dantd hinzuweisen, daB einige Autesen bei scbwierigen psychomotorischen Tests keinea Ein- fluB von CO-Konzentrarion von 50-250 ppm gesehea habea [3, 4. 16, 33, 411. In den USA sind kurrlich die Hinweise binsichNCb der Wirkung niedriger Koazentradonen von CO zm sanstnengefaBt uad ausgewertet warden durch das "National Air Quality Criteria Committee of the Nafional Air Pollution Control Administration" [42). Der folgende Absata ist der publizierten SchluDfolga rung diesn Beratungskommittees entnoawen: „Eine Exposition von 8 oder mebr Stunden gcgen- aber ciner CO-Konzentration von 12-I7mg/m' (10-15ppm) fOhR xu elnem COHb-Splegel von 2-2,5°6 bei Nichtraucbern. Diese COHb-Konzentra- rioa kana mit gesuadheitsschfldlichen Wirkungen in Verbinduog gebmcht werden, wie an dem beeiatr3ch- ngten Zeitintervall-Untencheidungsvermogen eaehee werden kann. Es sind auch Hinweise daf4r vorbandee, da0 eine Exposition von 8 oder mehr Stunden gegen- uber einer CO-Konzeatsation von 35 m8/m' (30 ppm) COHb-Sattigungsgmde von etwa 5% bei Nichtrau- :nern bewnkea Diesa COHb-Konzentratiou bewirkt den pathologischen Audall psychomotorischer Tete. Es gibt Hinweise dafir, de0 htlhere COHb-Kommmar liottaa phyeiolosuhe Stresa-Situaponan bei Patientea mit Herzlrrankbeiten bewirkm k6nned'.Wie benitg ew8hnt, entaprechen diese Kon7sntrr noneo daf Qronu dq ~rimPwvignsed a~paa°°°t -' treshold limit value" von 50 ppm filr eine 40 Std- . Un bei: rd„ Chh bu 1vi 0. boi mi als au F, At rer M. dc H Ik dc nc ra In zu Ei: ak TIFL 0305617
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.---~ Ul~LA UN:YERSITY Oi C4IFORNIA, LOS A[JGELES D~'ite a( Pal$Iic !n(ormation 1p5H118udA.enue • iLosAntela,Calilonia90024 Dial: ~'UCL1-59S Release NOT BEFURE: Wednesday, June 26, 1974 Al Hicks - 825-0519 UCLA GETS MAJORIRESEARCH GRAHT FROM TOBACCO IHDUSTRY A five-yea>` independent research program on lung defense mechanisms and early detection and t>Tleatmeut of cancer has been launched at the UCLA School of Medicine with the support of a $1,700,000 grant from the tobacco industry. Companies supporting the project are Brown and Williamson Tobacco Corporation, Philip Morris Incorporated, R.J. Reynolds Tobacco Company, the United States Tobacco Company# and Tobacco Associates, Inc. In a joint~listatement, the tobacco companies said: "This major new grant expands our sup~ort of independent scientific research. It reaffirms our efforts over the past tyro decadee to resolve questions about smoking and health in the only way possible --!by independent scientific research." A tobacco fompany spokesman added that grants of similar magnitude have recently been mede to medical schools at Harvard and Washington (St. Louis) Universities. . The resaarfh at UCLA will be conducted in the Department of Medicine and affiliated departments. Dr. Martin Cline, Chief of the Division of Medical Oncology and Hematoiogy,~lwill direct the program. The division already has an active program in chemotherapy~and i®unotherapy of cancer. "The provifiion by theee companies of research funds is an important development in bionadical rpseareb," Dr. Cline commented. "Such support is critical in the exploration of navel approaches to human disease and asaential for promising young medical scisntists in an atmosphere of intellectual freedom." Dr. Cline said the research will be concerned with the defense function of the lungs and the piriasible influence of various factors on these defenses. A major emphasia vlll bR on the study of a possible relationship between tobacco and disease, PA - 000509 -more- -rou::069s TIFL 0305683
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2 Tt1L t'RACTt7IOh£R :p(c prxisinn should Bc madc tn a(lose the increasinC umnber of non-, o4crs to brcal6e sir fr:v frWU 1tul:utiun by'tubaeeo suws•r: [rmlur:cft6rli.(wrsGeuup-. Dr. C. \(. Ph:eLeq M.D., F.ILC.P. (Chnirm:nl. Rn.a) Postenduato 1Ted'td - luw(} Dc.1. \)'. D.muc.n, )(.I7:, !'h.U., Lt,nJon :.hnol oi I•le:-rnu al.i Trnpica( ~ ( -' ' ' ' P \Callr )(edia icine: I ro4vor 1 1 lalhr \LD FItCP )(r R ...c..,........,. exrelt Cmmail3 Air Potlucinn ltaerrh l:ait and Dr. K. P. Ifall, \l.l).. FAC:S'. „ . e7), Gnua1 Vid.:1.~.x LleapitaL ~ ' J(tfCfClee3 . ~ . - . _ hrfln, T., anJ Ossll, O. IL (rq67): Cc.rrr aa, taSB, rmi4:e, A. K., And Tumer, 1). )L (t97o): Nauus (bond.), nb, ra3s. . tsu4. P. (te17-): iLit. n.e?. ].. IY, 447. ' , Kklds.n, K., and ll':mstnlp, ). C. (t~o):.Inn.'N.Y. Arud SeL s7.(, ar}{. ~: iref, S. \I., Cismtelli, S. Jr., And \luellv. )L (t97o): 1(dd..17J.-63. esr, fi W. IL (tq661: :a (:auadian StudY of Snw(dns uid t(mWs: Uspasmrooto6 ~ .'asionnl t(rJth ud )Cdiue, Ottawa. innio, W. H., Cu.v,n, R.:1., Hi(l, C.. 6., and ^x'aFer, .L £(197s):~ Swd&s oA : \lediml and Ponulatinn 5uhjren' Na. zb H-MS.O., IAndon. .. .,. acics, 3L F., And Day,T. pe(s9G6): BL.7. Co.iei. ay 363- oll.It(InGo):JtL(..n.w - - (sq; a): 'Catuzrs ralated to smn4(ne" in'The Semnd [Cur(d Confmsnae as . Smouln(•. nnY tlealttY, t'91man AIttLt9t l'uWUq14 " Ln4 1AYdaf). D. tC. ~ .nd1R11,e\.It.(t9fi+):Aeis.araL1..(,137D. ' ~ sen, W. u.. anu wuumu s. U07a/: J. oar. ta.ai Ima. ya. t7gS.=: . ' ammom4l_ C. (:gGG): \ ut. Caurrr Jm7..lbt.e~ No. tA p. ta7:: And HvnyD. (rn:k1: L,lne.. u,ed slv._ t66. Ixaa_ A.. tt. p hnro4 Il..wf. ...A. tN..l.. ..n_ - ^ " amnm+, JL and IiR.nhantr*, !: (rea. LfyR. n. JJaf:C- r4& 333. :. 3ambutCee, F- TnYerr, dA, aud )A4ar, 1. R. (t563): J. va6 Caaser Irt. 9. . . 1MIS• - hn, FLA.(v]W):.,\rt1.Canrrrr.nr.d)uw.,'r.,:O.iq,p,1. - nhbavm. A.. snd't)d(et S. (sN+S): CerinHirr.:?, ea6. .-"_ .... . non.:'. S- I!a:" H. O.. and Sllcetsc. !!. (t95a]:'Tdaaee.ve E.pzrimnttat =d'-- Clinial Stwlin, p. soS. . nreher, P. J.. and Cannsuu, It. T. (ttre)7 An,:. ,1r.Y. Arad: Sd, t7{, qi. . auay, IL D. GL:c~etore, u)kurbrieA-5nulh, D., arvd Jona,tt, (ty7s): 8rte . med. Y., (v, x05. . . na. D. ]L (tnss): dwr. df(nr.. tE. m.r.' . . .. oaek D. (tnt8lc [frit 7. Sun:._ 6. r.6. bortsen, D. G., tt'ussel4 0. d.. X.utao-Jonr. 1. 3, . And F(arLQ, G. a7- - (tq6q): lrnr. tvN. j, iiM ~6.j. . .. u , usau, ai A. tt: CJu, P. \'.. And ncewa, C. (a973)• za.rar. i.rrS ~ . ha0iro, Sr \t'uinblan, E, Frank, C- lt'., mrt saser, R. Y. (s969):.Ztw. X yv6LJl(d4,$% suppl.,June. . . . _ , __ ..~ pwr, F. (tq(S): 'Itch. weiewn..17(rL, 36; i;3.. . _ rch. 7lL (rn6+1: Otrd1.7 rn. ee.irht..)led_ 60. fle. -' eWi, ~ P. 1tq731:'3utuun el 3cw.mQ w tGe vmtau twruumr avw.aw . Itasavtls Caunsil. Londun. .$. Public )iahh Snrvicv t tq6ry): "the LTralth Consaquanm eESmnenq',19G9 SuppWnene m the sq67 Publ(e Itcahh 3cirnce Raristv. t'tt8 Fublioeioa ~a. . xGq6-a,elnptert. (1970- "tAa t(a1tS Con.equence af Smohinlx:.l Rapas os aSo Suel.'eon GanetA', DFIL•)~ PuLliatias \a. (t18~t)TMSt7, A't^6-+' (N7)1): tN.L.7:-7AG. C!uptur K. .. - 1wdet, E L. (toTa):7f nne Ctuerr lurt.. aS. r7.p1. . . .. , _ . s esW 1(Mfman, U. (Iq67):'lwb+ca and cuqacce Sn+wo",.~namu6rray. . New 1br4 and Lnndon. p. is3. .,. ... - uumuy ll. t\L ((0o)t.Lrn..AUtr:Y,=S, 37 s•
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HARVARD UNIVERSITY RELEASE; WEDNESDAY MOHN2NG, aECEMBER 27, 1972 UNIVERSlTY NLWS OFFICL OIaECfOR OF MF.OICAL iNfORMAT1ON 25 SHATTUCK Sl7lEET aOSTOY, MASS. 02115 P6nu: RE 4-3300 A five year investigation into pulmonary and cardiovascular diseases has been launched by the Harvard Medical School with a grant from the following tobacco companies: American Brands,~!~Inc., Brown and Williamson Tobacco Corp., Larus and Brothers, Inc., Liggett and Heyefis, Inc., Lorillard, Inc., a division of Loew's Theatres, Inc., Philip Morris, Inc., R.a. Reynolds Industries, Inc., the United States Tobacco Company, and the Tobacco AssociatRs, an association of tobaceogrowers. • The studyl~lwill be.conducted in the Harvard Medical Unit and the Channing Laboratory of the Boston Ciry Hospital with Gary L. Huber, M.D., Assistant Professor of Medicine, as the principal in{~estigator. Franklin H. Epstein, M.D., Professor of Medicine, is head of th^_ Medical Ul~tit and Edward R. Rass, M.D., Protessor o: is eir^r*nr of the Channing Laborat~ry. Drs. Epstein and Rass, with Ramzi S. Cotran, M.D., the Frank Burr Mallory Pro£essoF of Pathology and Head of the Department of Pathology at the Hospital, will serve as pr~ject consultants. Some 23 olkher investigators are now working !:ith Dr. Huber. "At this tiz:e, wa already have an i extensive research program concerned with the effects of environmental influences on.th~ lung." Dr. Huber said. "Among a variety of other environmental influence! to be studied, a~tention will now also be given to any specific effects cigarette smoke may have in the pevelopment of such pulmonary diseases as emphysema, chronic bronchitis, and lung cancer,llland in the development of heart and vascular diseases. While it is common knowledge that cgarette smoking has been alleged to be a major cause of these diseases, many other factol~s, not so well publicized, may be important. These include exposure to air pollutantthe Senetic differences in host suseeptibility, and so on. 'A direct (more) PA - 000508 ~ 002~sy3 TIFL 0305680
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U LA ~ Release UNIVERSrfY OF CALffORNIA, L09 AN6ELFS 0~'ice of Polblic Information 10`i Hilgard A.enut •i I Lm Angela, Califmoie 90027 Diil: "VCLA4BS HOT BEFORE: Wednesday, June 26, 1974 A1 Hicks • 825-p519 UCLA GETS MA)ORIRESEARCR GRANT FROM TORACCO II7DUSTRY A five-year independent research program on lung defense mechanisms and early detection and treatment of cancer has been launched at the UCLA School of Medicine with the suppoYt t of a$1,700,000 grant from the tobacco industry. Companies 'supporting the project are Brown and Williamson Tobacco Corporation, Philip Morris I'~corporatsd, R.J. Reynolds Tobacco Company, the United States Tobacco Companyli, and Tobacco Associates, Inc. In a joint,t statement, the tobacco companies saidc "This major new grant expands our suplport of independent scientific research. It reaffirms our efforts over the past two decades to resolve questions about smoking and health in the only way possible --~,by independent scientific research." A tobacco~,icompany spokesman added that grants of similar magnitude have recently been made to sedical schools at Harvard and Washington (St. Louis) Universities. The rsseattch at UCLA wi11 be conducted in the Department of Medicine and affiliated departments. Dr. Martin Cline, Chief of the Division of Medical Oncology and Hematology, will direct the program. The division already has an active program in chemotherapyf and immmotherapy of cancer. "The provi~sion by thue companies of research funds is an important development in biomedical s;assarcb," Dr. Clins commented. "Such support is critical in the exploration of~!novel approaches to human disease and essential for promising young medical stientiste in an atmosphere of intellectual freedom." Dr. Cline~ Isaid the research will be concerned with the defense function of the lungs and the poseible influence of various factors on these defenses. A major emphasis will h'e on the study of a possible relationship between tobacco and diseasee mo e rU(I::U696 PA - 000509 TIFL 0305683
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® ® m am ® ® ® I 0 1 1 UtiiN 750 Np '11l-•IrO1C/iL IIUVARY , UIl!IV JF "!1wNF5UT4 oI=HL HnIL KIrlvEnpOLIS NIw 55455 0 1 9 r1 i ,d I 5 I .f W U U W a+ F 'eZ:Y:s~'ar4 a
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. SUdavelbein: Einflu0 von Tabakrauch auf die Morbidiut von Nichuauc6em 237 Der inbaliereade Rauch rauth also sehr wirkun die umgebende Lu(t abgi Hauptstromrauches bei ist oichts bekannt . Der exponierte Nich - die den Nebenstromrau „filtett" den Hauptstrom- oil, bevor er ihn wieder an 2 IIber die „Filtsadon' des Ausblasen dureb die Nase ucher atmet also Luft efn, enthalt und den Teil des Hauputrotruancbes, der durch den Raucher wieder ausgealmet wird. Der obaliermde Raucher atmet oaheru den gesamten Ha ptstromrauch ein, einen Teil dm Nebensttomrauches owie cinen Tell des Raucbes, den ar selbst und eventue I andere Raucher ausgeatmet haben. Der Raucher, d verbindungen auf, wele in dcr Muadh6ble und resorbiert werden sowie ntotuell andere RauchDa Pfeifen- und Zi innalieren als Zigaretten Zigarettenrauchern tine mnen Hauptstromrauch Die Entstebung des pliziettea physikalische gen, tine Ubersicbt Obe und Filtration gibt N bindungen sind Im Tab Der Rauch kano untert und die Gasphase, eau beJinden sich die einzel beiden Phasen. TabeUe Uber die Zusammen Gasphase. r nicht inhaliert, nimmt die aus dem Hauptstromrauch eus dem Nebenstromrauch o Raurh, den cr sdbst und ausgeatmet baben- rremaucher weniger hiofig aucher, geben sic gegentiber relativ grof3en Anteil ungefil- an die Umgebungsluft ab. hakrauches unterliegt kom- und chemischen Bedingun- Bildung. Zusammensetzuog th (341. Nahezu 1000 Ver- rauch nachgewiesen wordea It werden in die Pardkelphase rechend ihrem Dampfdruck a Verbindungen in einer der und 2 geben eixo lyberblick ung der Partikel- und der Tabelle l. Z=mme setrung rkr Partlkelphase des Haupu¢omra hes. (Naci Neurath (34D Wasw 10-20% A1ip6atische Kohlea rrrerfe 3- 5% ?.ramatischeKOhleo entofte 1% C.vbonylverbindun 8- 9% Alkobole 5- 8': Ester 1% Saurm e-13% Hasm I :a Niwlinalkaloide 6- 8': phenols 1- 4% Sterne 0,5- 1': Tabelle2. Z der Gaaplwe des Hauptstrom- 4urhar (waperfrci) . ' he Gue. (Naeh Smokiu8 acd H th (38D stiekstnff 73% Sauartoff 10% Kohlendioxid 9,5% Kchleanoono' 4,2% Wmsaotoff 1% Fdelaaee 0,6% Aaunoniak 0,03% Slickoxide 0,03% G7aowaslCratt% 0,16x• Schwetelwss t aH 0,(k14% le,nytl 14.ltlae Welche Konzentrationen an Raucbbestahdteilen konnen nun erwartet werden'" 1.1. ,Vtcottn Harke [17] fand nach dem Rauchen von 42 deut- sehen Blend-Zigaretten von 85 mm L-ange und 18 mm Filter in 16-18 min und ein Abrauehen bis zu einem StummN von 25 mm in einem Raum mit einem Vohs- men von 57 ml einen Nicotingehalt von 0,57 mg/m'. Mit guter Luftung fiea dieser Wert auf ungefafu 0,10 mg/m' Nicotin. Des Rauchen von Zigarren (9 Zi- garren eines helkn Sumatra-Tabaks, in 30-35 min ge- raucbt) in demselben Raum bewirkte dne Nicotin- konzentration von etwa I mg/m', wi(hrend Pfeiten- rauch (3 g Navy-type medium cut-Tabak, geraucht als 8 Pfe(fea in 35-40min) eine Nicotiekouzentration von etwa 0,5 mgJm' bewirkten. BeiOftung des Raumes mit etwa 400 m'1Std bewitkte ein Abfallen dieser Werte auf 0,38 bzw. 0,10 mg NicotiuJm'. Cano u. Mitarb. (7] fanden oach dem Rauchen von im Mittel 109 Gauloise in einem 66m' fassenden Raum eioe Nicotinkonzentration von im Mittel 0,032 mg Nicotin/ms Luft. Nach dem Rauchen von 179 Zigaretten eines Typs mit hellem Tabak fanden die Autoren im Mittel0,037 mg Nicodn+ma Luft Diese Autoren geben an, da6 die LOftung des Raumes in einem „gescblossenen System" erfolgt sal, leider k6n- nen jedoch keine Angaben iiber eiae eventuelle Ftl- trierung des Rauches aus der Arbeit entnommcn werden. Beim maschinellen Abrauchen von 30 Zigaretten in einem 38 m' gro0en Raum faaden Harke u. Mitarb. [IB} in einer Sammelperiode zwisehen It und 75 min nach Rauchbeginn eiue Nicodnkonzentradon von im Mittel 0,51 mg(m'. Bei diesem Versuch waren Fenster und Turea fest gescblossen, nach 90 min waren die Nicotinwerte bei diesen extremea Bcdingungen auf im Mittel 0,26 mgJm' abgcsunken. Beim Abrauohen von 108 Zigaretten durch II Raucber in 2 Std wurden 0,11 mg Nicotin/m' in ainem 170 ms groBea Raum ge- messen. Es ist darauf hinzuweisen, da0 die Arbeit von Harke u. Mitarb. besonden gut kontrol6ert durchgo- fiihrt wurde, und daD Angaben, z. B. zut LTiftung, der relativen Lufdeuchtigkeit, Windrichtung, Windge- scbwindigkelt usw., der Arbeit enmommen werden konnen. Der von einer Sonderkommission der Deutschen Forschungsgcmeinschaft I968 festgelegte und vom Bundesmiaister fur Arbeit und Soaalea herausgegebe- ne :vfAK-Wert (maximale Arbeiuplatzkonzeutration) fur Nicotin liagt bei 0,5 mgJml, d.h. von dieser Kon- 2 Im folgendea wsrden haafig die Konttmratioampbm in .,ppm•' semaeht. Diae Angabe bedonat „parta oro miniae", alsu LB. bei Gasea I mVm' Lutt, ba Manm 1 mglki. Da be( der Bezeichnung ppm nicht erkeoabar ist, ob das Hwwnan elne Maua odee ein Volumea irt, sollte diesa Braichnuaa oicbt mehr verweodet wetden, dtiedoch aucy noch utfmdk Angaben, wie Ln. die MAK-WerOe in eee aeemcht werden, sog eie filr dlaen Bailna tolerial weedee. - MAKzmaxinrab Arbeav platzko>u<ausdon. TIFL 0305614
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242 ~ H. Scb;evrlbeio: Eisdlu0 von Tabakrauch auf die Motbidislt von Nichuauchem inr.mer ser Meinun zu Hnden. Wilbert (441 kommt zu dcm folgendm hlnH: „Bei dem bohen Prozentsau von Rauchern ter Patienten mit arteriellea Verschl(tB- krdnkhaite crscheiat uns die Diskussioo Gber das sog. ,,passive R uchen", d.h. Eiaatmen von Nicotin in stark verra htm R3umen (Wirtshausatubea, btfent- liche Ver 'uel oder Konferenzs3le) unerhebtich°. S.ICesuedheitsachidBche Wtrkmgm der pas.tivm Inhalstlon von Zigarettemaeeh beE Tkrm In der 'teratur wadea zahlreiche Versuche zu die- sem 7hema beschrieben. Die Exposifion von Venuehs- tleren ge dber Zigarettenmuch ist bisher durchgo- tl5htt word a, nm Ver3nderuogen an Organen zu er- zeugm, di denjenigen ahaeln, die bei Mmschen auf- tretea; im esentGchen dieneo sie der AufkliTung der Atiologie d Bronchialearcinoms. Aus diesem Grunde sind die Ra dosen bei dieseo Versuchen so hoch, dag sie mit d menschlicben Passivrauchen nicbt mehr vergleicbb sind, sic sollen deshalb bier nicht be- sprochen rdm. Der Referent schliegt sich der Met- nung der merikaoischen Wissenscheftler an, die in dem la "Report to the Surgeon General" (s. FuB- note zum stel) zu folgendem SehluH kamen: ,,Die se digende Wirkung des Ranches bei diesca Tierexpe ' enten wurde nach 18ngerer Exposition gegeaiiba hohea KonzeatraEionen von Ztgattttm- rauch beo achtet Es ist aicht bekanat, ob eiae Ver• gteichbark it der Tierversuche mit der Exposition von Measchep in rauchgefullten R9umen gegeben ist So ist m gege wartig aicht mdglich, von Tierexperimenten auf da.s A maB der Sch9denzu schheBen, die wahrend einer Ian auernden, aber intermiHierendcn Exposi- tion gege mlber niedrigeren Konzentrationen von Tabakm beim Menschen vor sich gehen k6nmmn". Aueh us eitta kritischea Obersicht von Larsen und Silve (29) eba die neuere Literatur zu der Frage, ob assives Rauchen Broncbialcarcinome indu• zierm ko en, ist kein positiver Hinvrcis zu cntoehmen. 6. ScBlagbemerk(mgm Dm rliegendea Untersachungea k6nnen Beweise fisr eisro G ahrdung der Gesundheit des Nlchtrauchers durch „passtve Rauchm" nicht eatnommen werdea. Es isi ieha, deD sich viele Nichtraucha dutch die Expositio gegemiba Tabakrauch in ihrem Wohl- befinden «intrschtigt fGhka. Nech da WHO ist Gesundhe t defiaiert als da Zustand, da nicht nur dutch das Fehlen von Krankbeitea and Gebrechen ge- kenrizeieb et ist, sondern atsrL duzcb das Vorhaoden- seia einp vollea physiologischm, gdstigeo und sozia- len Wohl etindms. Wean man diese Definition akzep- tlert, so i der Niebtrauober, der sich in einem Raum mit Taha nch mcht woal[Ublr, nicht mehr gesund. Zweck dieses Berichtes ist, eine Bestandsaufnahme =unserer Kenntnisse zu dem Problem „Passivraucheak .C• vorzulegen. Es venteht sich von selbst, da6 Spekuly . tionen und aus SpekWationea gezogme Konsequenree :~ keinen Plaiz in einem wissenschaftlichen BeriUlt fih- A den. Es erscbeint notwendig, auf diesen Sachverbalt -; hinzuweism, deen selten wird auf einem Gebiet des arztllchm Bereiches mehr spekuliett ala auf dem Ge, biet „Rauehen und Gesundheit". Es wire wiinschenswert, da0 die Unrersuchuope * zu diesem Problem iate0siviert und erweitert wiirdrn, 4 insbesondere verdient nach Meianng des Referenmo -, das Kapitel „Biologische Wirkung kleiner CO-Kon. zentratlonea bei Einwirkuog Uba laugere Zeit" be. soadere Bedeutnng. Literuur I. Andabub, H-P., Hofa, P., Scheaer, M.: Schwdz med Wschr. 100, 739 (1970). 2. Asnup. P., Kjeldsen, K.. Wensnup. ).: 1. Alherostla. Rea 7. 343 (1967). 3. Baek-K. C.: Proa 51hAnnual Cosdaessce on Atmaphesic Contaminatlon 1n Confined Speceq Sept. 1969. 4. Back, K- C, Deminr~ A. ]l.: Prea 4th AnnuQ Cnn- fettnce on Atmospheric Comaetinanon in Confined Spacm, Sem. 1968, 5. Beard. R. R, Graadnaff, N.: Am N.Y. Aced. Sci- 17,1, 385 (1970). 6. BIa1r, W. H„ Henry, M. C. Ehrlkt, &: Aech. earironm. Hlth Ig, 186 (1969). 7, Cano, J. P., Catalin, 1., Badr6, R., Dusnas. C., Viila, A, Guilbrm0. R.: Am pharm. fmns.2a. 633 (1970). g. Cobom, R. F., Fors[a, R. E., Kaee, P. B.: J. din. lnvar. 44, 1899 (1965), 9. Dalbanlq T., Edfurs, M: L., RYlandar, R.: Arch. eavi,oom. Hlth 16, $31 (1968): und 17, 746 (1968). 10. Donrenwih, W.. Hark4 H: P., Baar0. A., Goertz, E.: Arrs- nNurinel-Fusxh. 21. 142((971). 11. DuBah, A. B.: Am N.Y. Acad. Sd. 174, 425 (1970). 12 Freeman, G, Crane, S C. Stephem. R.1., Funosi, N.1.: Amer. Rev. reap. Dls. 98, 429 (1968). 13. Freeman, G, HaydoM 0. B.: Arch. env4omn- H1rh 8, 135 (1964). 14. Freeman, G., 3tephem, R.1., Crane. S. C., Furiosi, N.1.: Areh, envircHIM. tUm. 17, 131 (1968), 15. GSIusklnovL V.: Neoplasma (Bfrnsl.) 11, 465 (1964). 16. Jlanb, T. 0.: Am N.Y. Aud. Set. 174, 42t (1970), 17. Harka H: P.: MWch-med. Wschr. 112, 1328 (1970). 18. Harkn, H: P., Baen, A.. Fnhm, B., Petert, H., Schuls:.Ch: Int. Arch. Atheiumed. 29,323 (1972). 19. HerkqH.P., Bleloben,A.: Zum Problem des Pasdv nuchms. Int. Arch. Arbeitamed. a9, 312 (1972). 20. Hayden, 0. B, Davidson, L T., LiBinaton, G. A.. Wssscr man, K.: Amer. Rev. reap. Die. 95, 797 (1967). 21. Haydon, G. B., Freemen, G., Furkei, N.1.: ArmL cn- vironm. HBb 11, 776 (1965). 22. HelluoFisrsen, P., Laune4 T., Kiddsen. K., AstNp, P.: 1. Atherosda- Rea. 8, 343 (1968). 27, Hess, H.: Reaeasba. Jb. aral. Fortbild. 13,219 (19651 24. Johaanon, C. R., Ronp,14.: Nordt hye. T, 47, 33 (1966)7 und 46, 45 (1961} 25. Kjeldsee,K.: Smoking end arhaosderors. Invesaratiuos on the sigoiBmm of tM nrboa saotso:ide ceuteot fn tubucw smeke in etberosenusis, Copnhagm: Munksastd 1969. 26. K)ddsen, K,: in 25, S.42, Z7. Kellq P. pelk, It, L: Cancer (fEned.) ra, Sso (t95o\ TIFL 0305619 .A~
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HUMAN PANCREATIC ENZYMES: CHARACTERILAI[ON OF ANIONIC HUMAN TRYPSIN Recently improved procedures for purifying human pancreatic prolesses have made it possible to delecl an anionic form of human irypsin, as wcll as to purify thia prolein and investigate its properties. The cnryme was isolated from acemne powden of human pancreas by salt Iraclionalion fullowed by ioneschange chrom.tugraphy on SP Sephadcx C-25 and on DEAE-Sephzdes A-50. The preparstion war homogeneous sa determined by disc detlrophoresis arul sedimentation equilibrium centrifugation studie., the laller also indicating an estimated molecular weight of 25,800 for this enaymo. Comparison of aoionic Irypain wilh the calionic enryme shows a high degree o1 similarily nm only in molecular weight, but also in the amino acid composition of each pro- tein as well aa PH optimum and ability to digest casein. The anionic form, hoaever, has only a weak cross-rcaclion with antibodies dirocud toward the cationic ensyme, and is much less stable Ihan that proteare. R is also rapidly inhibited by soybean trypsin inhib{lor erd. lo a keaer eatanl, by porcine Kuet pancrealc inhibimr and ovomucoid; all three are paor mhibitars of c.lionic trypsin. Mallory, P. A. aod Trnvlr. !. BiachemiAry 12(IS):2847-2851. 1971 , Other anpporl: National Institutes of Health. From the Ihpanment of Biochcmistry. University of Georgia, Athens. tion of exposure, indkating that both an: caused by a combination of the nicotine in particulales and comlitueno of the vapor phase. The decreased pulmonary compliance was elicited by inhalation of fresh whole smoke but not by Ihe gas-vapor phase. This would indicate that the uusative faclor is in the particulate matter, probrbly nicotine, because thr appearance of decreased compliance depended un the nicotine level. The decreased tidal volume as well u increased pulmonary raistance, or bronchospasm, occurred nqre readily in ICR strain nriue Ihan in the Swiss strain. Both strains developed Ioierancr: to bronchnpasm a/ler ten weeks of exposur<. These waa no increase in functsoml residual capacity and, heace, no functional sign of pulmonary emphysema in mice that had been eapowd to cigarette smohe for five or ten weeks. Arfedo, D. M. and W atanabe, T. Toxicology and Apphed Phorrtracology 30(2):185-200, 1974. From the Department of Pharmacology, University of Penmylvarua School of Medicine. Phihdeiphia. I PUNCTIONAL AND BIOCHEMICAL EFFECiS ON THE LUNG FOLLOWING INHALATION OF CIGARE7TE SMOKE AND CONST77UENTS. II. SKATOLE, ACROLEIN, AND ACETALDEHYDE Daily exposure of mice to 1he gm-vapor phase of cigarette smoke for Bve or 1en vrceks has elici[ed broncho.pasm aod decreases in functional residual capacity. To help pinpoint the causative factors of theae effects, three ano- a~~ of the gn-vapor phase, skatole, acelaldehyde and acrolein, were AND BIOCHEMICAL p.FFECfS ON THE LUNG FUNCIIONAL tetted in male Swiss mice. Onl ingestion of statuk caused pulmonary con- POILOWINO HIGH- 1NHAI.ATION OF AND fAW CIGAREy7E -NICOTINE SMOKE AND CIGARETTES Besrwn thal was maoifaled by an Increase in pulmonary hemoglobin content CONSTITUPFNTS. 1. IN MICE and a deueaae in pulmonary phoaphoOPidc Then was no increase in functional residual capacity and, hesloe, no pulmonary emphysema in mice that had either Thh atudy has examined the effects of chronic inhalation of eigarctte ingesfed skatola or been adminisured an intratraclreN injection of papain. The smoke In two strain, of snhs, ueing lechniques previwaly developed by theu: latter procedure nufed dcenases In pulmonary compliance and in the anti- iuvestigaton for measuring puhmnary function in this species. The Influence trypsin activity of the blood, both of which are coincidentally seen in human of aging was investigated prior to determining the effects of smoke inhalation. forms of pulmonary emphysema. AcenHehyde, the second constituent of The nicotine content of the cigarette and the duration of exposure were varied cigarette smoke studied, when Inhaled by mice fer Bvr weeks caused a reduo rn ex tion in tunGional ttaidual ea eily sirml.r to Ma1 erlcwntend in mice ex- eRect relationship beMeen cigarette smoking and chronic obsgructive pul- pded to the gas-vepor phase ef cigarNrc e. e n, ud com d Inunary diaeue. Daily inhYatqn of cigarette smoke for five or hn weeks whose elle.da are herein reporKd, caused a reduction in pnhmnary cumpBaace, did, however, cause the following: (1) incrcased pulrnonary reshrance; (2) but this effect is not seen in mice eaposed l0 the gas-vapor phase of cigarette Ran«smoka de ed funeGan.l tmidual ca aeil •(3) de ed uhnon. cum crcm p p a y P ry ue (4) decrcased tidal volumn; and (5) inaeased wet weight of the lung nlalive lo reduced body weight. There was no change in phosphalipid contenl of the Im1g. The incre.ae in puhnonary resistance and decrease in functional residual capacily wen ehciled by rreshh whole smoke as wcg as by the gas-vapor phase. 7Dey were also related to Ose nicotine content of the cigarettea and 1he dura- ?V0~06S1 26 Watanabe, T. and Avfado, D. M. Toxicology and Applied Pharmacoingy 30(2):201-209, 1976. From the Deparlmenl of Pharmacology, Univenlly of Pennsylvania School of Medicine. Philadelphia. 27 TIFL 0305638 I
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Rosae, R. and Rare, C. L. Journal of Nealrh d. Sociaf Behavior 14(4):381-3g7, 1973. Other support: National Ckaringhouse for Smoking and Health, U- S. Pul~ lic Health Service. From Hellenic College, Ikookline, Maa., and the Veterans Administration Out- patient Clinic, Boston. EFFECfS OF AGE UPON RETRIEVAL FROM PRIMARY AND SECONDARY MEMORY There ia a demunstnted leammg-memory defkit that is associated wilh advanced age, and it has been proposed Ibat retrieval processes account, at least in part. (or this age-related de8cit. To teat this experimentally, the retrieval processes of young (X = 21 years) and old (A = 56 years) subjects were compared in bmh primary and secondary memories. Subjects of both age groupa conducted aerwl and exhaustive retrieval searches in primary memory. The speed of the young subjects' searches was about twice as fast as those of old subjects. Similarly, all of the aubjeets conducted serial and eahaustive searches in secondary memory. AN searrbes of secondary memory were akwrer. Young mbjccn, however, maintained Iheir speed advantage over old subjecls. Theae results demomlrating the old persom' slower retrieval searches In secondary memory, in combination with Ihore In primary memory, extend the scope of the original proposal that retrieval processes accauN, at least In part, for Ihe leaming-memory deficit of individuals of advanced age. Andera, T. R. and Fozard, 1. L. (Bclf, B. and Rose. C. L) Developmental Psychology 9(3):411-415, 1973. Other support: U. S. Department of Health, Education and Welfare and Canadian Department of Nationa/ Health and Welfare. From Ihe Depanment of Psychofogy, Dalhousie University, Halifax, Chnada, and the Veterans Adminutralion Outpatient Clinic. Boston. EFFECTS OF AGE AND STIMULUS REPETITION ON TWO-CHOICE REACTION TIME in this study, mak voluntmn, ranging in age from the 20's through the 'l0's, performed a two-choice reactiosaime task. The subjects released one key wilh the right hand upon presentation of a red light and another with the left hand when a green light was presenled. Each stimulua occurred an equal number of times in a sequence of 40 triah, but the probability that il would do so twice in succession was only .25. Mean response latency increased with age, although varnability did not. Stimulus alterations were generally responded to more rapidly than were stimulus repetitions- This "negative recency" effect / tJtXl7(fl~ 64 0 is cunsistcnt with an eapcclancy theory of choice-reaction time, airsce stimufl and responses were repeated only rarely. Older individuals responded as rapidly, or even more rapidly, to altemtions than did younger ones; they were evidently guided to a similar extent, therefore, by the sequential dependencies inherent in the series.af signals. Although the older men were indiv{duafly more variable than younger ones throughout the coune of thc.eaperiment, they were more honsogenous as a group. An analysia of the frequency dk- trihutiam of response latencies suggested that the older individual's longer choice reaction-time reflects impaired psychomotor rather than decistiun-making efiriency. -PauTN: C: ea aT. loanwl o( Geronlobgy 28(4);466-470, 1973. . Other aupports Veterans Adminiatnlion and National Instilulea of Healrh. From Ihe Department of Psychiatry Research, Massachuselb General Hospital. Basaw. FACTS AND FICTION ABOUT BEHAVIOR CHANGES WITH AGE: IMPLICATIONS FOR THE CONCEPTS OF OBSOLE9CENCE AND VITALITY AS APPLIED TO Tf1E ENGINEER Section 11 of Maintaining Technical Competence in the Older Engineer deals with behavioral changes associated with aging The major,purpooe of thie article, and of two othen in this sation, is to provide background infor- malian about behavioral aging. AII Ihree articles .tresa that chronological age itself is not a auMcient basis for understanding individual differenm in the behaviors labekd technical obsolescence or vitality. They also point out that concepts such as obsolescence and vitality have little ulilily either aa descriptive labels or as guides to action when their meanings are restricted to the work role of au individual. In order to understand the meaning of obsokscence, the totality of the interena, morives and personality of an individual developing through hit middle years mual be taken iplo account. The present arlfde, moreover, in addition to presenting a framework for interpreting social and psychological aging, goes on to make some general reoommendationn, related to obsolescence and vilality, to Ihe individual engineer and to the urganiration which employs him. Forard, 1. L. (Bell, B. and Rore, C. L.) In: Dublin, 8. S. and Shelmn, H. S. (eds.): Matntaining Technical Comprrrnar in the Older Engineer, Washington, D C- American Society for Fngimering Education, 1974, pp. 55-71. Other auppnrl: Normative Aging Study of [he Boston Veterans Adminialra- lisn and National Institutes of Health. From Harvard Medical Schaol, Bnston, and the Veterans Administration Out- patient Clinic, Boston. 65 TIFL 0305657 i ~
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semativa of the di/lerent racial groups. Not only is infarmalion being obtained on smoking experience bul on s wide range of environmental exposures and ora:upational activities in relation m morbidiiy and mortality. The twin rcgis- tries should provide a valuable suurce tor many other studies that will include the effects of multiple environmentd variables on individuals of iientical geno- types and during Ihs process of aging. 3lrsdiea on familial predisposition to d'nease are also being done. The teodency for concers to accur in sorne farnmiiies is greater than in others. This tendency may be restricted IV cancers of cenain sita or to two or Illore siles. The predsposition of peraons with known genetic comtitutioos so acquire emphysema also has been drmonsVated and may be causrd by deficiency of a wbsance or substances that inhibit proleolylic enzymes. Individuals with this genetic deficiency. fortunately only a small percent of the population, are par- fipdarty vulnerabk in "mmg" environmenb. psrsphysema aiso ouurs in iMi- vlduals wBhuul this specific geoetic defaiency: a special risk indicator is pto- .ided by the family history, an indication that other unidentided genelie deter- minart; of prediepoei/ion may eaist The epidemiological projects of interest to Ttie Couneil Involve mostly prospective atudia of selected populations that pto- vide special contrasts for genelic or environmemai similarities or diHerersm. Buic research is aisn being funded on the chemical identiticNlun of proleasa and their inhibhors and how they inlerect. The leveb of praleases In dNerent organs and in rnamai, embryonic and cancerous tissues are being mrsdied. FurtBermore, exlenai.e efona are being made Io improve she AHH aasay, ssing human tisua, to promole its application to human epidesniologi- wl atudia. Wilhout basic investigation, the improvement and perfection of amafytieaf sechniqua and the developmcnt of new or modified concepts of disease prevention or control wiN be limhed. Wu.t.usa U. Ganmsn, Px.0. Scientiflc Director Cancer-Related Studies Among the diseases that heve been associated statistically with cig.rctle smoking in population studies, carcinoma of Ihe lung has apparently received the greatest Ntention. Nevertheless, this disease oceun only in a small mhar- ity even of heavy smoters. This emphmius that research on its pathogenah must include consideratiun of possLle substantial dilferenua among individuals both in their genetic eharacteristics and in the numerous condilioning ingu- esrca to which they han been subjeclcd. Many anomalous and contradictory aspecu of the epidemiotogicar findings have been described, and the gmat di/hcuhy of conducting human sludia with comrols adequate for resolulion of thesc anomalies has been recognized. The masom for thu are both ethical and pnclleai. Hence, the crucial questions "whether, how, to what extent, under what condirions- and In whom" smoking could contribute to pathogenesis of the disease remain unanswered. An dterrx4ve approach to the problem of describing the Interactions of intrimic and extrinsic hduenw in the process of cmcioogenesie lies in the design of suflabk model syslems involving animah, animat tissua or cells ar, in some isatances, hurnast tissues or cells. Superficial aperimenu with irwde- quately degned species or straim- whether whole animals or their tisua or cella, will twt aolve these problerm. There u slrong basu for doubling that muu.e .kin painting wilh etored condensata of the particulate phase of smoke, aihred in physical asate and in chemial compoaitioo and laeking most com- ponents of the gas-vapor phase of "trhoir, fresh uormal smoke," can establish, defirse or quanNtale the "carcinogenic hazard" of smoke IrtANalron by mao uoder life mnditiom. The design of auch model aystems is a most exading enlesprise, since the question of the applicabiiily of ihe results trom tlrese models to man ]n his actual environmeats must be asked at every sqge and eventually answered. The Councii haa, navpthekeM, undertaken 10 develop a series of model sys- tems for the plssptaes muslwned and lo explore slrategia for relating the resrdb to nuu. - Carcinogenesis as a MalgfStage Proeua Though the term "earcinogen^ h often applied to indivWual chemical canpomsds or mixWres an if "carcbmgenicitj" were a specific or unilary prop- erry of matDer, like a molecular weight, an absorption spectrum or a dipole moretnt, It Is well-known thal this w not Ihe cne. Induced cudnogenau is ----- - ------- - logical syalems of the hmk Ttsees:, in tu.n, are presumed In depend both upon Nse initial, gern;ticagy influenced characteristics of these systems and also upon a seria of separate actions by ahe aalernaf inciting ageot or agems that require quite specific physical or chemical propertia and cosrdiliom. Such agents havt habitually been grouped together as "carcirpgena" or "poteutial cueinogens." Neverlhelep, it is wel4known fhet a"cardoogen" for one specics, strain or tiusr under particular clrasmstanees, may not be a"eercinogen" for another specia, strain or I:sue, or qnder other oircumstasrcea. Metabolic modi8cation may be necessary to convert the external "pnlen- 7 TIFL 0305628 l
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suring lysosomal iermeabiiity could be used to detect early stages of cell dam- age. As pan of a continuing study of Ihe direct toxicity of various agents on From the Department of Surgery and Medicine, Temple University Health speeific cardlovascular eeBS and of their paaiblc rok in the etiology of cardfo- vamular di¢mq Ihe authors describe a method for meauring lymsomal fn- gjlity. The results are reproducible and wn be tested for statistical significance. Cultured neonetal rat heart endothelioid cdla were used to evaluate hypoxia. nicutine, carbon monoxide, and hyperoaia far their potential labiliring efkcls on /ysosomes. Although all lrealmenn were trsxle in that they reduced cell mr r, on y mc me ' - eoneentratiorn tested. The increased lymsomal permeability produced by nlco- tioe was followed by extensive ceilular .ansolation. and the reaction was both time- and coneeolration-dependent. While hyperotia affected a similar change in lysosomal permeability, the increase wu rapidly followed by cell death- These results, however, do not preclude the possibitity that nh:otine, hypoaia, or carbon monoxide might interacl to produce effects not seen with any of Ihese agents alone. Wened. D. G. and Reed, B. L Rrrearch CommuNcarionr in Chemkaf Pathology and Pharmacology 7(4):745- 756 1974. Other snpporfe U. S. Public Health Service and University of Kansaa Oen- eral Research Awards. Prom the Department of Pharmacolop and Toaicotogy. School of Pharmacy, University of Kansu, Lawnnce. THE PHYSIOIAOY OF STRONG EMOTION: CANNON'S SCIENTIPIC LEOACY RE-EXAMINED In this paper. presented on the occasion of the 16th Annual Bowditch Lecture and the IIXlth anniversary of Cannon's birlh, the author recrounls some of the scientific events shaped by Bowditch and Cannon which have led to current concepts about behavioral control of physiologieal phenomena. As a young researcher who had rlarted x-ray observation of perist.1lic waves at the suggeslion of Bovyditch, Cannon observed sotrMhing during the course of his gastrie motility studies which caused him to deduee that excitement might pro- voke a gow of adrrnal medullary accreeion, ud that changes originally in- duced in the digestive orgam by omvom impulses might be continued by cir- eulating adrendin. Three techniques that Cannon later introduced to study this emotional production of drentdin were based on: (1) an adrenalin bioassay. (2) the supernormal sensitivity of the dcncrvNed hean lo circulating adrena- lin. and (3) removal of the cerebral corlea which caumd "a sort of sham rage." Througboul hia adnnat<molioo studies. Cannon described the pbysio- lygical IrKehanisms wherein behavioral phenomena might promote organic disease, described what is now called the "defense-atarm reaction," and postu. 61ed the dekterious organic effects of physiological reactions in modern man uoable to counter enviromrrmd threats by physical activity. This hypolhesis Tu0zo6ss 42 was qill not thoroughly tnled a we entered the 70's. but there are now experiments under wny at Harvard Medical School which suggest that beha- vioral phenomena may induce organic disease. These experimrnls are fully described In this paper. Using squirrel monkeys as subjects primarily, the au- thor and other investigamn slarted studying the long term dlecls of behavioral phenomena. Because the cardiovascular system responds quickly to environ- mental stimuli. they used continuoru meantremeMS of systemic arterial blood pressure and heart nx to quantitate reactions to varioua behavioral prooedurea The objective of these exprriments wu to induce consistent cardiovascular ~;-tlrae--- behavanl procedures which pr most effective in producing hypertenaire responses are being tested for their possible rok in Ihe pathogenesis of hyper- tensive and uleriosderotic cardiovascular disease in aubhuman primalea. in retrospecl. Cannon's hypolhrno dut strong emotions might induoe organic disease seeans entirely reasnnabk but It has taken 60 years m develop La havionl techniques for eaerting sustained control over physiological phno- mena. The idea stated an Cannonl diary that pathologicaf eRects of emolian are due to failure to have ruwmaf exit in muscular movement can now be tested prospeclively in snbhuman prinsasea. Herd, f. A. (Barger, A. C.) The Physiologist 15:5-16, 1972. Otker anpport r U. S. Public Health Service. Frum the Department of Physiology, Harvard Medical School, Boston. IV. Neraropharwaruotosy rurd Psychophysiology TOLERANCE TO THE EFFECTS OF DAILY NICOTINE ON RAT BAR PRESSINO BEHAVK3R FOR WATER REINFORCEMENT In Iha rat, chronic nicotine admintalration (0.25 mg/kg nicotine tartrate, (.p., twia a day for 15 days) caumd initial disruption of bar pressing behavior for waUr reMforcemem, followed by rapid development of tolerance. Beouse ndcollee aku causes Ike release of anlidiuretic horenore (ADH) which migh( reduce the animal's drive for water reinforoensent. the autlsors leared the effect of ADH administration (5-10 units/kg. a.a) as well. Since, in contrast to nico- tioe. the hormone mppressed water drinking behavior only after an initial period of latency, the authon conclude that nicotine has a direct effect on h.r pressing behavior which is unrelated ro the release of ApH. and that daily exposun leads to tolerance. Domino, E. F. and Luta. M. P. Plraimarology Biorhemhtry and Behavior 1(4) :445-448, 1973. From the Department of Pharmacology, UniversNy of Michigan, Ann Arbor. 43 TIFL 0305646 FA
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1 Hung, K. S, and Lovdr, C. G. The Amer'san Journal of Anmomy 140(2) 191-2UB, 1974. Odae/ aarppost: Environmental Protection Agency. Howard Hughes Employ- tea Oive Once Club, and the Hasrings Foundation Fund of the University af Southern California. From 16e Departments of Anatomy, Pathology. and Medicine, University of Saulhem California School ol Medicine, Los Angeles. tls uptake ard removal of partieles Ihau The fymp)satics aad seem lo pl.y a amRrypsin Irom sab' b w)Ifs phenolype Pi.a- In this improved melhod. Ihree MECHANISM OF ACTION OF a-l-ANTITRYPSIN ' Biochemical evidence auggetn Ihal a-l-anulrypsin has two inhibitor sites, one containing a positively charged residue and the other an aromatic or leucine residue, with both sites having a binding site for the active moiety of seaine pratesses. Experiments designed to test this hypothesis show that: (1) trypsin and chymotrypsin compete for inhibitory siles on puri8ed a-l-ami- trypsin, suggesling that the inhibimr has Ihe aame or overlapping inhibitory siles for there Iwo enzymes; (2) trypsin inactivated by di'vopropylphosphoro- 8uoridale fails lo occupy inhibiting sitrs on a-lanlilrypsin: (3) a-l-anUlrypsin inhibits sublillsin, a proleolytic enzyme Ihal contains serine, hislidine, and as- partic acid residucs at ils active site in common with mammalian scrine pro- kasea; (4) a-l-anlitrypsin fails to inactivate aoelylclmlinestuase. a noapro- Ieolylic enzyme whose active aile contaim a reactive serine residue, suggeslissg that this residue alone if not sufficient for inhibition by a-l-antitrypsin: (5) treatment of a-1-anlitrypsin with phenylglyosal hydrate blocks in adion on Irypsin but not on chymotrypain, a change in activity which is presumptive evidence that arglnine residues were modified by the lreatna:nt; antitryptic saivify can be regenera(ed wilh removal of the blocking groups. -liscse results are consistent wllh the hypolhesis that Irypsin and chymotrypsin are inhibited at Iwo different dles on a-l-anlitrypsin and wggut that the trypsin inhibitary site ctmtains a positively charged amino acid. Cohen. A. B. ~ The Journd of Bioloyical CAemtnry 248(2)0) :7055-7059, 1973. Other suppon: U. S. Public Health Service. From the Medical Serviu. Sen Francisco Oenual Hospital. and the Specialized Center of Research and Department of Medicine, University of California. Snn Francisco. PURIFICATION OF PHENl7fYPICALLY UNALTERED ¢-1-ANTITRYPSIN tldes an smn In micropinocyloslc vesiclea and toared vesklea: (5) blood This procedural paper describes several modifications of the, method of eyrllaries in the inler-alveoiar sepla are morphologically much leas adapted for Shamaah and Rimon Ihal enable puriflcatiou of phenolypically unchanged a-t- THE ROLE OF THE PULMONARY LYMPHATICS IN THE DEFENSES OP THE DISTAL LUNG: MORPHOLOGICAL AND EXPERIMENTAL STUDIES OPTHE TRANSPORT MECHANISMS OF INTRATRACHEALLY 7NSTILLATED PARTICLES This paPer, which also contains a brief «view, of the authon' earlier studlu en the mittoscopk analomy and ullraslructure of the pulmnnary lym- phalict, presents an expuimental study of the uptake and removal of intm- /rarheally inatilkd carbon and fearhin particles fran ihe alveoli of ne.)man rabbitt. Resulss abow that: 11) in the alveolar lumen, terriain panicha mia rmteh rrsore easily with Ihe surfactasl material than carbon pnrllcbn, allhough both are pbatpscyhaied by alveolar macrophages and neutrophBS: (2) since the alveolar eells are lightly interwnnclyd, forrtnng an impermeable barricr, the tracer parlielea can reach the inlerrntial turuc comparlment only by a Iranf- txtlular ronla. Type I alveolar edls reem to have a veskular type of Innspott for ferriun and carbun, with laidy 4rge numben of (errilin molecules being phagoeytiaed and apparently dtgawed m¢c,aa/ary sysosomu: type 11 alvedar cdh alsophagucylias both uacers, upecially fcrrilin, strongly suggaling a double guoctiw /or thn w11, namely awetion (e.g.. surfaclanl) and phagocy- raw (e.f.. Ierritin, carbon and lamtllar material); (3) interstitial connective Ihaue ulla of debatable origin also contain phagocyliaed carbon or ferrilin particles; (4) the tracers very rapidly appear in the lymphatic lumina mainly through shs open imeroellular lymphatic Iunetlom which act as inlet valves arnqled by ghe anehoriag Blameou. Lyssrplutie endothelial oeih also phagoey- Iine feariUa panicln In large vacuolea and secondary lysoammms: ferritin par- caYed Clara celb, are also eapable of phsgocyliring ferritin moleculea. Iaawsryns, l. g!. and Baert, l. H. Arana6 of lfse Nen York Academy o! Scfene<s 221:244-275, 1974. Fmm Ihe Laboratory of Hialopathology, Kalhdieke Universiteit tn leuven Sehoo) o/ Medicine, Leuven, Belgium. mnvsd bP ciliary activity; (7) the bronchiolar noncilieled rylindrinl, or ao- m carbon; (6) many particka ne relaused within the lerger airwayr to be re- and alcohol concentrNlans, anion-exchange column ehromatography. and pre- ~ 0020643 pua6ve polyaerylartsidt gel electrophoresis. All the modiflcatloos described herein occur in the lhird technique. This method results in recovery of an average of 12.1% of the trypsin-inhibiling capacity of the scrum. The a-[- amitrypsin prepared in this manaer nainl.ins the heterogeneity in acid starch gel-immunocronsM gel ekurophoreaia that chanrclerius o-I-amitrypsin in whole suum. This observation provu Wat the phenotypic characteristics am not dependem upon serum factors. Alm, this purified inhibitor resemHes a-I- antinyprio In serun mote closely than n-l-anlilrypsin prepared by previowly, 23 TIFL 0305636
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that both acetyichoiine and melhacholine preunt the release of IsHlnoradrena- line ('H-NA) by nicotine in the gninea-pig perfused heart and show that acetykholine fails m release sH-NA from the perfnsed heatl except when used in vcry high wncemrati,ma (10-0M). However, if atropine (lOsM) is added to Ihe perfusion solution. 1O eM atstytcholine will readily release stl-NA. Theee results are comhtent with the given hypothesis and demonstrate that muscarinic agonius also decrease the release of nondrenaline induced by aico- tine Further, evidence is presenled suggesling that the muscarinic inhibitory receptors are much more sensitive to acetylcholine than are the niwlinic reeep- mn. This reporl, therefore, supports the coneept that Ihe muscarinic inhibitory mecaanirm :rls s nf r g lan rine tM releatn_p(_npridr<nlift- WesQaH, T. C. and Hunler, P. E. lonrnal cf Pharmacy und PAarmacobgy 26(6);458-460, 1974. Otker support: U. S Public Health Service. Prom the Departrnmt of Pharmacology. University of Virginia School of Medi- cine, Chulottesvilk. SPECIFICITY OF BLOCKADE OF THE NICOTINE-INDUCED RELEASE OP sH-NOREPINEPHRINE FROM ADRENERGIC NEURONS OF THE GUINEA-P10 HEART BY VARIOUS PHARMACOLOOICAL AGENTS There is now convincing evidence (hat, in addition to many other egecls on the nervous ayst<m, nicotine and related drugs can induce a direct release of norepinephrine from adrenergic nerve lerminals. A large number of pharma- coiogk agenu, however, have the ability lo block this nicotint-induced release of norepnephrine. Among these blocken are hexamethonium, morpNne, co uine, brelylium, fidocaine, phen.xybenzamine, and damethylimipnmine. This study uxd perftaed guinea pig heans to compare the ability of several of Ifsese agents to after the releass: of nicotine-induced norepinephrine, in order to ob- tain isfonnallon oo the mechanism of this blocking action and to aesess hs specigcity. Tyramirte. KCI, sminophylline, and prostaglandin Es were also studied, as were proslaglandin Er and calchicineq which have recently been ehown to decrease the release of nompinephrine after nerve stimulation. The following agents inhibited the nicutine-induced release of sH-nnrepinephrine by more dran 90%: hexamethonium- morphine, cocaine, bretylium, and lidopine. Cocaine and bretylium decreased the rekase stimulated by lyramine, but only lidowirse lowered that induced by KQ; none of these agenls blocked the stim- ulating effect of aminophylline. Cokhicine significantly decreased the nico- tine-iMuced rehase, but not that induced by tymmine or KCI, Prmtaglandins Es and pa. however, decreased the release of sH-norcpinephrine induced by nieotine, KCI, and amirsopbyllinc, but nut that produced by tyramina. The com eiwione are that: fl) lidocaine biocks the nicotino-induced release of nor- epinephrine by a local anca0setic action on the adrenergit a:onal membrane of the pnoea-pig heart, whereas hexamethonium blocks the nicotinic receptor; (2) cocaine, bretylium and morphine block the nieotinic receptor, or acl at aorne later slep between receptor activation and norepirtephrine relene; (3) T o0;:U662 48 colchicinc appears to havc a specific anticholinergic effect in decreasing relcase of rsorepinephdne; and (4) prostaglandins Es and Es both decrease the release of norepinephrine at a step in secretion coupling common to nerve stimulation ard the administration of nicolinq KC1 and aminophylline. WearJad, T. C. and Brasted, M. ' , TAr )ournal oJ Pharmamfagy and Experimental Therapeuticr 1 g9(3):659-1i64, 1974. Other aapport: U. S. Public Health Service. - _ -. - Pan. lbe DepindrreM-Of-Plsarmaealn$y. IlmverS11y6f-V~INa ga`_-~ _ ~.(lda--- cine, Charlollavilk, EFFECr OF AMINOGLUTETHIMIDE ON NOREPINEPHRINE TURNOVER IN THE RAT HEART I r Ammoglulelhimide, which interferes with cholesterol side ehjin cleavage in the conversion of cholesterol to pregnenolorw, has been shown to inhiblt synthesis of all adrenal steroids of biological activity. With this action, amino- glutethimide could be a valuable tool in enabling ane to selectively inhibit adrenal cortical steroidogenesis without significantly disturbing Ihe (uncUOning of the adrenal medulla. fn this sludy, Ihe authors attempted to inhibit selectively the adrtnal cortex with aminoglulethimide and thus to determine the extent of involvement, if any, of the adrenal eortex per se in the control of synthesis af norepinephrine (NE) in the rat hean. To do Ihh. NE turnover was measured by two different methods in male Sprague-Dawley rats. Results showed Ihat inhibition of adrenal sleroidogenais with amitrogeuelhimide does not change eodogenous NE levels in the rat heart, does not influence cardiac aH-NE up- take in the ral, does na a11er the urinary excrelion of epinophrine or NE, but does result in an increase in lumover of cardiac NE when injecled for six or ten days at 200 mg/kg/day. Similar observations have been made follow- ing adrenakctomy and hypophysectomy. Adrenal cortical insufficiency is a common denominator of all three of /hese experiments. Results here also indi- cate that the increased cardiac NE turnover is not seen before six days. This slssdy, thetefore. succeeded In demonslraling an increased turnover of NE in the rat heart on inhibition of adrenal teroidogenesin with aminogluletMmlde. This adda to the evidence that there is an interaction between the adrenal cortex and NE Iurtwver. West)nU, T. C_ and I<wis, T. C. Procetdings of the Socierr for Experirnenrnl Biology and.Nrdicinr 142(4):1295- 1300,1973. Other aupport+ U. S. Public Health Service. From the Department of Pharmacology. University of Virginia School of Med't cine, Chirloltavitk. 49 TIFL 0305649 9
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CORTICAL CUPS FOR COLLECTiNG FREE ACEfYLCHOLINE IN AWAKE RATS The conical wp procedure, which is becoming on increadngly popular lechnique for collecting the acetylchuline spontaneoudy released trom the sur- face of the cerebral corlea, generally requires that throughout the experimcnl du animal, be either anesthetized or immobil¢ed wilh a neuromuscular blocking agent. This paper, Irowcvcr, describes e method for the collection of aeNyl- choline samples from the cerebral cortex of fredy-moving rata with dsronicaily brIanud bilateral cortical eup. The tnnmarent nylon cum remain mabk for at lusl two months after implantation and will hold enough L.ackee solution /or the xelykholine rekared In a l5-minute period to be analyzed by the leed muscle bioassay. The fact that the release of acetykhotine Increased after nkotine administration (0.4 mg/kg i.p.) iltustratea that in rala the melhad is suitable for determining dmg-induced altetations in neurotransmhter release during on-going behavior. in addition. when It Is combined with appropriate chemical or bioassay methods- the technique is potentially useful for collecting other putative neurmransmisters released Iram the cortex of the rat. Erkkmn. C. K., Onham, D. T, and U'prichard, T. Pharmacofogy, Biochrmirrry and Behavior 1:743-746, 1973. Orherswpport: National Institute of Mental Health. From The Department of Pharmacology and Toxicotogy. University of Kamas Sdmol of Pharmacy, Lawrence. STRUCIURE-AC7TVITY RELATIONSHIPS FOR THE BESERPINE-LIKE ACTIONS OF DERIVATIVES OF A-CARBOLINE IN VITRO Although the experimerds reported here were underlaken to determine wherher physico-chemical facton play a significant rok in the activity of A- carboline derivatives, The resultant data suggest instead that it is the structural speciheity of the she of action that determines the derivative's activity. tn this study, the abgitha of 10 derivatives of j3carboline to canperilively inhibit the ATP-Mg++arisnWatcd uptake of epinephrinc wcre examined in isolated rat adrenal meduliary storage vesictes. Uptake was inhibited 72% by hnrnine, 64% by harmaline, 59% by Lmethylhannine, 43% by barmd and 25% by harman. Norharman, 6-melhoaylrarsnaq 6-rrrethoxyirMole, 6-melhoxytetm- hydroharman and yohimbine did oat inhibit epinephrine uptake, nor did any of the 10 derivatives affect metaramirrol uptake. The potencies of epinephrine up- take inhibitors werc unrelated to the lipid solubiiiry or pK of the drugs, sug- geating that difference, in activity reflected differences in aRmity for the cate- cholamine transport site. Harmnt, 2-methylharmine and harmaline were them- eelves incorporated into the vesicles, bul their incorporation was less dependent on Iemperamre than that of epinephrine or metaraminol. These data suggest that j;~carbuline derivatives iuteracl with a calccholamine carrier on the out- side surface of the veaick membrane and that the attachment involves at least T 00Z06(;3 50 thne portions of the molecule. The different structure-aclivity, rrelationships for inMbition of epinephrine uptake v<rau uptake of the (f-carboline deriva- Gves themselves indicate that two separaie processes, inward tramport and subsequent intnvesicnlar binding, contribute to the meaeuted uptake. Slotkin, T. A. Li/e Sciences 154 3): 419454, 1974. Other aupport: Amcrkan Heart Association and Faculty Developmenl Award in Pharmaeology, from the Pharmaceulical Manufacmren .>\ssociation Foundaroo. - From the Department of Physiology and Pharmacokgy, Duke University Medi- calCenter, Durham, N. C. DRUO-RFSISlANT EFFECT OF ADENINE NUCLEOTIDES , AND MAGNESIUM ON CATECHOLAMINE EFFLUX FROM ISOLATp.D ADRENAL MEDULLARY STORAGE VESICLES Adenine mscleotldea and divalent ulbns han vital roles In Ike uptake, storage and release of catecholamines from adrenal medullary vwiclea The flKOtporalioo of amines ime isolaled vesides is slimulaled by ATPP and mag- rsesium (Mg++)- which have alsu been implicated in The mechanism of cale- ebolamine aeaetion. Rexrpine inhibits incorporation of amines. The inlra- veakutar storage complex probably consists of four molecules of catechola- mines combined with one mokcuk of ATP. A question which the aurhors are attempting to answer in Iheir series of experiments on Isolated rat adrenal storage vesides is whether ATP and Mg++ directly affect the rale at which aminn leak outward aaose Ore vealck mcnsbnne. Their data support prevlous observaUom that adenine nsrcleolides, divalanl catiom, and reserpine decrease the binding of calechdamines to prsrified adrenal storage vesido membrntea. Results ahoau0gest that: (I) egkas of catecholaminn from the vesidm Is not a simple digmlon process but may requlre the interaction of Ihe amirse with a specific component of Ihe ve.kk membrane; and (2) the reduction in amine eglux produced by the addition of A1P and Mg++ may result from Inlerfer- eoce with this Inleraclion. According to the authorr, these studies demonstrate thaf ATY ond Mg++ reduce amine Mlut by a mechanism Independent of Its uptake into the vesicfu and not blocked by drugs which inhibit uptake; thia effect may play a role in the stability of catecholamine storage. SlnsHn, T. A, and Oreen, H_ O. Biochemical Pharmacology 23:2190-2192, 1974. Other aop ort: U. S. Public Health Servir.e. American Heart Association and North CaroPna Heart Association. From the fkparl.rrent of Physiology and Pharmacology, Duke University Medical Center, Durham. N. C. 51 TIFL 0305650 ~
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RESERPINE-LIKE EFFECTS OF HARMINE ON ISOLATED ADRENAL MEDULLARY VFSICLFS Because of its strucnsral similarities to reserpine. the actions of harmine on adrenal medullary vesicles were examined in order to clarify the mechanisms involved in drug eRecb on amine uptake and storage. Harmine markedly in- hibited the ATP-Mg++-0ependeM ineoaparatian of epincphrine into isolated ral adrenal nsedullary vniclea The inhibition (g5% of epinephrine incorpora- Bon) was both competitive and reveraibte. in wnlrasl !o this, melaraminol In- corporation, which is prcdamimnlly ATP-Mg++-independenl and reuapine- imetsciY.~wsdecreascd-oM9 23%: Hafmrne a no e on e ux o epme- pM1rine from adrenal medutlary vesicles- indicating that the effect on incorpora- tioo was due solely to inhlGlion of uptake. No temperature-dependenl uptake of hamine imo the ve.ides waa dete<Ied, implying that the eRecls on the up lake aysrem are purely inhibitory. Thi. report also describes dre effects of harmine on the binding of amioes to vesicle membraou and ih effects on severJ of the enzymes involved in epfnephrine bimynMesh and degradalion. The data suggest that the Pcarboline group of the harmine and reserpine slruc- lure b responsible for the aBinily with the amine uptake mechanism and for inhibilion of uptake, while the remainder of the raerpioe mnlecuk confers irreversibility. A mobife carrier In the adreml vesicle membrane may be the site of selion. Green, H. O, and Sfurktn, T. A. ' Molecular Pharmacofogy 9(6):748455, 1973. Othersnpporl: North Carolina Ilon Associatlan. From the Department of Physwlugy and Pharmacology, Duke University Medi- csl Cemer, Durlum, N. C. V1. Immunolo6y anrl Adaprinu Mechanismg STIMULATION OF HEME OXYOENASE IN MACROPHAGFS AND LIVER BY ENDOTOXIN According to the evIdence presented herc, endoloxin slimulates heme osygena.e (HO) in macrophagea in vitro and m liver in vi.ro. The activity of this ma:msomal enzyme nystem, which converls heme to bi/irubin IX. is nor- mally stimulated by heme and hemoproteim, presumably reflening substrate- mediated enzyme Induction. The stimulation of HO by endaloxin, however, ap- pears to iovolve a mechan'sm which may dpfer from Ibis type of hrduclaa In rN perironeal macrophages engaged in eryahrophagocytosis in vhro, emiomxin stimulated HO adivity which was additive to the enbrlnlr-mrdiated enzyme induction produced by Ihe ingested erylhrocyte henwglobin. Endnloxin did not appear to injure the erythrocytes; nor did it enhance the rate of erylhro- pMgocylosh. In intact rau, endotoxin IreatmeM increased HO activily in both parenchynsd and sinusoidal cells of the livet. It is likely that endotoxin slimu- lates HO activity directly, which may necount far the reponcd rise in bilimbin r VutiussQ 52 formation in endulaxin-1rcaled animals. This effect an HO may represent part of the general activation of phagocylic cells by endotoxin. Oemsa, D, Waa-C. H.. Fudenberg, H. H- and Schmid, R. The loureol o/ Cfinicnllnvestigarion 33(2):647fi51, 1974. Other au(rpora: National Instilutes of Health and the Walter C. Pew Fund for Gaslrosntestmal Research. - - r:hc-•^efa•::..en:~f cinc, San Francisco. BIOCHEMISTRY AND HIOZ.OGY OF COMPONENTS OF THE PLASMA KININ-FORMING SYSTEM The author deBnea Ihe.Inleractiom among various components of the ptasma kinin-forming system, with particular emphasis on Ihe mokcnlar char- acteristics of kallikreln and Factor X1 of the blood dnuing ayslem. He de- scribes a human prekallikrein degssency previously known as the "FklcM1cr factor" coagulation abnormality. In the absence of prckailikrtin. neither the inlrinsic clotting nar Ihe fahrinolylic system is ade9ualdy aclivaled when plasma is exposed 1o gloss. This observation, coupkd with other laboratory data show- ing that kallikrein activates Hageman faclor- prompts the author to propose that this enzyme mainlains optimal rates of coagulation and gbrinolyais through its reciprocal aclivalion of Hageman faclor. Wrsepper. K. D. (Cochrnne, C. G.) In: Lepow, 1. N. and Ward, P. A. (eds.): Inllamrnnrion: Meohnni.v,u nnd Control, New York: Academic Prers, 1972, pp. 93-117. Other supportc National Multiple Sclerosis Sockly and U. S Public Health Servia. From the Department of Exper:nenlal P.Ihology. Scripps Clinic and Research Foundalion, La Jolla, C.I. THE STRUCTURAL CHARACTERISTICS AND ACTIVATION OF HAGEMAN FACTOR The structural characteristics of Hageman factor, the parent component of the intrimic clotling. kinin-forming, and hbrindytic syslems, have been characterized. The subslarsce has a molaolar weight of 80,000 and it is aelf- vared in both solid ard fluid phaxe. In the solM phase the molecular conBgu- ration ctsanges, exposing enzymatic sitn. In Ihe fluid pha¢, on the other hand, enzymatic activation induces molecular cleavage yielding enzymalicnlly active fragments. Plasma enzymes capable of activating Hagernan factor in the fluid phase include kallikrein, Factor XI, and plasmin. Each af these is part of a system ectivated by the parent molecule. Thus, there is a reciprncal acthalion of Hageman factor by its subsltates. On a molar basis kallikrein possesses the greatest activity in this regard. Solid state activators include vascular basement 53 TIFL 0305651 r~
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197J ltS H , e 1(.Ir., g°- ren ga- 'pt- die der Jn- Ot :re .1ie rb. be• -n• im (n. er- le- :in °'- ro ing .len ich mg eo, in- mg :n• :ng ist FDkdose sdiwane Zi a 1,la ma Nicada im He n. Die Befunde von Harke u. Mitarb. werden gestutrt durch Untersuchungen von Cano u. Nfitarb. [7]. Diese Autorea fanden bei Rauchversueben Ausscbeidmg von Nicotin bei Rauchern und Nichtrauchern in dir gleichm GrbBenordnung. 2.2. Dfe Aufnahme con Kohfenmenoxid belm parstoen Reuchen Die Aufoabme von CO bei cincm Individuum hangt naturlich von der CO-Konzentration in der Atemluft ab, daruber hinaus von weiteren Patametern, so z. B. vom COHIrAusganganivezu,von der physiscbm Titigkdt und viel[eicht auch von dem Gesundheitszu- stand. Die Einstellung eines konatantcn Zustandes zwischen dam CO-Gehalt, der der Lunge angeboten wird, und dem COHb•Gehalt bendtigt etwa 12 Std Exposition. Die Halbwertszeit von COHb bctr3gt zwi- schen 3-4 Std. Bei inhalierendm Rauehern kann der COHb-Spiegel bis auf 10% ansteigen. Bei dem vor- [iegenden Thema interessiert das COHb-Niveau, das bei passiven Rauchern beobachtet werdea kaun. Die Frage ist schwierig zu beantworten, da eine ge- wisse Vorbelastung wohl itnmer gegebm ist. Die Frage ist auch noch offm, ob physiologischerweise aucb ohoe Exposition ein gewisser COHbSpiegd vorhanden ist. Anderhub u. Mitarb. [1) fanden bei Nicbtrauchern, weEche keiner feststellbaren CO-Exposition ausgeseta warm, ein COHb-Niveau von 1,4-2,4%. In dieaem Zusammenhadg sei daraut hingewiesen, daB die Aoa- lytik geringer CO]Ffb-Konzeotrationen keiueswegs be- fried[gend gelost ist. Ein unter extremm Bedingungm durehgefubrtes Experiment, das hereits oben erwahnt wurde, wurde von Srch [40] durohgefBhrL Er beobach- tete, daB das COHb-Nfveau bei 2 Nichtrauchera von 2 auf 5% anstieg, wenn die Versucbspenonea in einem Auto saBen, in welchem durch Rauchm von Zigaretten efne Koozentration von 90 ppm CO in der Atemluft herbeigefuhrt wurde. Bei den Rauchern in dfesem Ver- such stieg das COHb von 5 aut ]0%'. 4 Sieha FnOnate 3. enn und Cotlain im Ham be( Rauchern und Nichtnuchem, Mittelwcie (usch Harke I171) rr KBrpv- gew cht Zigatten- vld Ham (mp pH Nieotin Cctinin (a'B) GrB) Re) (yro Penun) L'uftung 7 77 8 800 5 622 577 tuna 6 66 9 1050 6,5 1160 906 treb ohne LOftunj 4 73 II 1100 5,7 1526 1199 «ea mit Littuaa 5 72 I1 3600 5,7 2198 1583 ) g 7 71 t1n7 5,9 W 34 7 71 1239 6.3 18 19 ptitromnuch. plalranrau4,. TIFL 0305616 H. Schievelbeln: Einflu6 voe Tabaknuch auf die Morbidilat von NichtnucMm 239 weniger als 0,02 ppm A oniak und an gesamtoxidie- rmden Substanzen (al 0zon bereehnet) weniger als 002ppm getunden. 2. Die Auhohme v n Tabakrauchbestandteilen In d Orgamsrnua Die Messung der ufnabme von Tabakrauch so- wobl bei den aktiven Is such bei pasaiven Rauchem steUt fiir die Forschun zu diesem Thema ein beson- detes Problem dar. ontenvdll u. Mitarb. [101 pra- parierten Zigaretten mit n-Hexadecan (n-Hexa- decan-I!'C) und IieO syrixbe Goldhamster pass] I v raucben. Danacb wurd die Aktivit9t in e(nze[nea Or- ganea gemessen. Bezo n auf die Flhchenanteile zeigte der Kehlkopt vor T chea und Lunge die hocbste AktivitAt, ein Befund, er die von den Verfassern frii- her getundene stArkate gewebliche Reaktion in diesem Bereich erkl3rt. Beim Menschen k" nm derartige Versuche eatvr- lich nicbt durchgefuhrt werden, als Ma8 fUr die Rauch- aufnahme bat man aher bisber nur Nicotin und Kohlenmenoxid unter ucbL 2.1. NteoNneuf hme hefm Passimauchen Aussagen uber die icotinaufnahme lassen sich nur indirekt durch Messun der Ausscheidung von Nico6n oder seinen Metabolit n machen. In der Tabelle 4 sind Ergebuisse von Harke [I7] zusammengesteB[. Es haodel6 sich u denselbeu Versuch, der obm unter 1.1 bereits g ildert wurde. In der Tabelle 4 siad :viittelwerto an ehen. Es erscheint auffatknd, da6 trotz der extre n Bedingungen (RaumgrbBe 170 m4), innerhalb va 2 Std Rauchen von 98 Zigaret- ten (obae Luftung) u d 108 Zigaretten (mit LBftung) relativ wenig Nicotin durch die Niclttrancher aufge• nommen wurde. Auff lend ist weiter, da8 die Nicotin- aufnahme, gemessen n der Nicotin- und Cotininaus- scheidung, steta hoher bei BelBfmng ist. Viel[eicht 1a0t sich dies durch eine re uzierte Bereitschaft zum Ziehen in dem nicht geliiftet Raum erkl5ren. Tahelle 4. N - p3,4 m> FrischluEt/Pcrw a' Filutlqa rcbwerac ZI SlmdNlerdaantlaa ohrm glendfilrerel9uetteamit !! (33.4maPrtschluftlPerse NichtraucherohoeLar f N46tnucha tM Lnnun ~ (33 s -, ,4m Frischiutt/Pene ( • 0,95 mg Nleetin im Ha [i
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Imernin 1 . ll. Jr.. Relt S, 1973 I H. Schierelbdo: fanflu0 von Tabekraur2l aid die Morbiditat ven Nchufurhem 24l ~ 4. Chro¢isdse bkiogfsche WMtsmg gesetzt. ;. Scnkung dieser G nze auf 25 ppm wird diskutiert. - In der BRD i t der MAK-Wert mit 50 ppm fest- Woche (funf 8 Sto-Tage), welche in den USA fur die - Iett<ea 7ahre vorcbrieben war ([l]. Eine weitere Passbtaneiena 1. drtesiasklerose :en Ea. wisehen ,nd5tarf ,eniiber und die relatis eobach- die Itrlch- rverhal- :onzen- )Hb mit bachten die Ent- to6ach- :hiuhen COHb. Nutoren en Ein- gesehen ichllieh CO zu- ch das of the ," [a21 :Sfolge- _egen' mgms al van lZenOrl- agen in mtrach- ersehen sacden, , gegea- - 0 ppm) chtrau- heWlrkt Teste. )zeatn• ,Heotea Izentn- adond -i0 5td- Dutcb die U ersuchungen atu dem Arbeitskreis om AstruP, Kjeld en u. Miurbb ise die chranisckte Ex- position gegenB CO als mbglicher Risikofaktor filr die Ausbildung e ner Arteriosklerose sehr Icbhaft in der letzten Zeit d skutiert worden. In eiaer Ubersicht fuhrt Kjetdsea [2 ] vevsohiedene Autoren an, die beim Menseben und ' Tierexperimeat nach chronischu Expositfon gegen' ber CO 6ber Herzscb-adigungen und Veranderungen in den GefBDea berichten. Kaninchen, chamitStandardfutter + 2% Chole- stenn gefilttert w rden uad zusitzlich einer CO-Kon- zcetntion von 0, 2-0,036% in der Atemluft ausge- utzt wurden, en wickelten bei einem COHb-Gehalt ron 10-20% $ were Arkriosklerosen der Aorten und einen signifi ant h8heren Cholesteringehalt des Blutes als Kontr ]Itiere [26]. Spatere Untersuchungen zdgteo deB die 0-Exposition per se schoa arterio- sklerotiscbe Vera derungen in der Aorta von Kanin- chen bewirken k [22]. Derselbe Ar iukreis berichtet ilber ausgiebige Untersuchungen zur chronischen Wirkung von CO beim Menschen Ubasicht, s. Kjeldsen (25]). Es besteht ei e s[atlstBch hochaigni[ikaate Kor- relation zwische dem COHb-Gehalt und dem Serum- Cholestennspieg l bei esner grdBerea Zahi van Pro- banden. Astrup [2] berichrete iSber 17 Rauchcr mit Winiwatar-Buer rscber Kraakheil, bei denen die 0,-Dissoziations urve nach linksverschobrn war, d.h. bei denen der s gerittger war ala bei 176 Fatienten mit aaderen Kra kheiten, unter denen sowohl Raucher afs aucb Nichtra cher waren. Die Verfasser kommeu aufgntnd ibrer Untersuchungen zu weitreichenden Folgerungen in ezug auf die Wirkung des CO fur die Atiologie der onarerk[ankungen und der perfphe- ren oblikrferen en Gefiflkranl5heiten. Sie sind der Meinung, da6 ' geschadigten Coronatien der 8lut- ,: durehflu8 nfcht rh5ht werden kann und dadureh der ,.# Hypoxia tsicht tgegengewirkt werden kann, zusatz- ` -' : Bche gerfnge M gen von CO kSnnen die Hypoxie d erart verstSr , daB akute SymPtome auftreten kdn- nen. Die ehroni he Wirkung kommt nach der Aut- ~a~ fassung dieses A beitskreises dmdt die SchSdigung der Ii ntma und der ockierung CO-empfindlicher Enzyme zustande, welch zu GefaBlBSionen und nachfolgender Etalagerung vo Fettmetaboliten fuhten kann. 4.2. Irrha~fonen ond a/fergfsche Reaktfalen be! Ni htrauckern unter dern ELrflu/i Von Ztgaretfenraaah Iohansson und Rouge (24] beobachteten, daB die akasaa Irritatidnen der Nichtraucher in Gegenwart von Tabakrauch in warmer trockner Luft als ma.dmal empfunden werden, und daB Nichtraucher mehr nasale irrimtionen als Reizaogen des Augea im Vergkich zu Rauchern vetspuren, die ahnliehen Kon7antratioaeIl von Ranch in der Atmosphare ausgesetzt sind. Speer (39] untersuchte die Reaktion von 441 Nichtraucbern, die er in 2 Gruppen teilte. Die eine Gruppe von 191 Personen bestand am Individuen nsft allergischen Reaktioaen in der Krankengeschichte und die andere aus 250Individuen ohne eine solche Aaamnese. Die Gruppe der Allergiker wurde hautgetestet hinsichtlich einer Uberempfindlichkeit gegenuher Tabskexuakten. Die Nichtaltergiker-Gruppe wurdc nur dutch eincn Fragebogen abgegrenzt, in welchem aach subjektiven allergischen Reaktionen gefragt wurde. Uegd-ahr 70% der Personen beider Gruppen klagtea iiber Imta- tionen der Augen, wShtend andere Symptome in fol- gender Reihenfolge der Hiufigkeit angegeben wurden: Nasale Symptome: Allergiker 67%, Nichtallergiker 29%; Kopfschmerzen: Allergiker 46%, NichffiBergiker 31%; Husten; Ailergiker 46%, Nichtallergiker 25% und Niesen: Allergiker 22%, Nicbtallergiker 4%. Der Autor meint, a handele sich wohl mehr um Reizungen als um allergiscbe Reaktionen, jedoch wurde dutch diese Untersuchung gezeig4 da0 Tabakrauch das Woblbefinden vieler Mensclsen beeintrachtfgen kaaa. Andere Autorea baben versucht, untar ihren Pa- tienten diejenigen herauszu[faden, die spezifische Allergien gegenilber Rauchbestandteilen besitun. Zussman [45] land, daB in einer zufz0ig ausgesucbten Gruppe von 200 allergischen Patientea 76% klinisch hypersensitiv, gegenuber Tabakrassch resgiertea; eine Mehrheit dieser Patienten konnte durcb elne desensi- bilisietmde Tberapie geheilt werdea. Savel [36] bericl>- tete kOrzlich tiber 8 Nichtnucher, bei denen eine klini- sche Hypersensitivitat gegenuber Tabakrauch bestand. Nach in vitro Inkubatioa der Lympbocyren dieser Patienten mit Zigarettenreuch wurde tine erhbhte In- korporation von Tritium-markiettem Thytnidin fest- gestellt. Die Exposition der Lymphoeyten von Nicht- hypersensitiveo ergab eine Verminderung der Auf- nahme von tritiiertem Thymidin. 4.3. Perfphere Durchbfuttmgssldrungen Die Frage, ob das passive Rauchen zur Atiologie der peripheren arterkllen VersohluDkrankheiteo bei- tragen k8aate, ist in der Icttrhen Zelt sehr beftig dis- kutiert wordea. Ausgelt4st wurde die Diskussion durch efnen Beitrag von Hess [23], der herichtete, daB unter seinen weiblichen Patieaten nur 50% Raucherinnen waren, im Gegensatz zu 99,1% bef Minnern. Unter den 60 krazlken Frauen waren 9, d.b. 15% IaagjShng im Gastst8ttengewabe tIItig, 6 von diesen Patlentinssen weren selbst Nichtraucherinnen. Hess meinte, dall dfee Beobachtung ein Hinweis auf eiaen mbglichen Risikofaktor „passives Rauchea" bei da Manifesta- tioo euws obGterie.mden AagiGpathie eein kbanta. In eiaer Ubersicbt tibcr neuere Litetatur zu diesem Thema (Larson [28]) ist jedoch keine Best9tigung die- TIFL 0305618
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REVERSIBLE DAMAGE OF RAT UPPER RESPIRATORY TRACI CAUSED BY CIGARETTE SMOKE Ikcause of the need to determine the spccific reaction of the maxillary glaM and slnus to an experimemally-induced environment, this preliminary in- ves4gation was designed m clarify: (1) the cBect of whole cigarene enakc on the rnuilkry epithslNm aod gland; (2) the progress of marphologic changes lu the epithelium and gland as a function of smoke dmage; and (3) the snm- phobgie changes in the epithelium and gland during the period of recovery. Adull Sprague-Dawky rats were cxposed to whole cigarette smoke for diger- eut pe.ioda of linae and Ihen sacri&ed at various stages of retovery. As studied under light micrmeopy, histologic preparaliom of maxillary sinuset and glanda showed seeeral changes: (1) the mauillasy epithelium lost columnar ciliated cells and hyperlrophied; (2) she aubmucosa displayed evidence of an acute in- ganmlatory reaction; (3) in addition to other morphologic modifications oc- curaing in the matcillary, gland, Individual goblet cvlls containing acid mucotub- shnas dlRerentiated within uew rmaillary epithelium; (4) eanvascular lymphocytes, polymorphonudear kukocytes, and macrophages migrated in great numbers from the aubmucma to the sinua lumen by way of the epi. thelium; (5) some mignting ceUa invaded the lumina of excretory ducm; (d) dse maailMry ainsn contained a mwive amouM of pur; and (7) micreahoesaea were scattered throughout the epithelium of animals expoad to smoke for a k>pger thrre. In spite of the morphobgic changea induced by the experirrreot- enernal stmeture vornd the maxillary sinus was re-established quickly aller cessation of smoking and througboul recovery. Vidic, 8., Raw, M. W. and BAosar- B. 0. Archirss of Orolaryngobgy, 99(2): a 10-117. 1914. Oa)ser support: National InsdwM of Menial Health and U. S. Public Health Seaviue. From the Department of Analmny, Georgetown University School of Mediclne, Washinglon, D. C., and the Deparlmenta of Anatomy and Phyaiule gy, Saint Louis Univessity School of Medicine, St Louis. CNANOESgN TRACHEOBRONCHIAL CYTOLOGY NOTSD DURING ANPSTHPSIA In thb trarbeobronchid cytologic dudy. smcan from 4.573 patients un- deqoing Broeni todolrarbeal aueqhesu were screened for the early dugnosis of sslements - bbl nuclear score, percentage of gohlea ccih, total cellular xore, pereem.ge eg muhimrdea(ed cdls - was nsade, according to Ihe patticular slydy in pogram. R.wlla fell either under the heading of ehaogea in cytology erwed by taeaWeia or cJnngtl in cytology coisa:ident to anrsthaia, and ehe foBowing phenoawna were discovered: (I) significant cylorrsotpkologic changes ocan in the epithdid celb of patients who inhale dry anesthetic gases for longer than nne hour; (2) the traeheobronehial epithelium undergoes varretions Ib mmphology which resemble changes found in the endometrium during the urmuuaf cycle; (7) iocreased numbers of multinucleated ciliated epitlselial celis and a generally higher degree of muhinucleation are found in patients wilh exlrathorscie malignancies; (4) cytomorphologic damage in smokers pre- cedes redactiom in lung funaion; and (5) tracheobronchial washings may be used to diagnose iohaqlional iajuries mstained in fires and, of course, tu dla- cover unsuspected malignant conditions of rhe lung and bronchus. CAdon. J. 1 New York Slare Journal oJ Medicine 74(12):1 t85-21 g9, 1974. Other support: National Cancer Institute and American Carr«r Society. From the Department of AncAhesinlogy, Alherl Einstein College 69 Medicine of Yeshiva University, 71re Bronx- N. Y. TRACHEOBRONCHIAL CYTOLOGIC CHANGES FOLLOWING LOWER AIRWAY THERMAL 1NIURY: A PRELIMINARY REPORT Eafeliativa cytology is a technique which might provide a relatively nnn- invnire, atraumalic meam of making a definitive diagnosis of the therrnal damage lo the lower airway etuaed by amoke inhalation. In this paper, the in- vesGgNon describe tnchrobroochial cytology from nine patients with over- whclming clinical evideoce of inhalasion injury sustained in fires. Cytology was grossly abnormaf in two patients; there was moderate evidence oP damage in four more casea; and smava from the lad three patients wbe normal. Them was a ptuitive correlation between cytologic damage noted In smeare and severity of clinical findinga during the Brd hospital day. Sequemq' I serid cy- tobgy in two patiems reflected the couru of the lesion during Ihcfepy. Thcse sesults appear very promising both from the diagnos4e and prognostic points of view. 71re method is eimpie, praeticd, and ineapmsive; perhaps it should be evaluated at other hospitala. Ambiavagar, M., Chafon, JL and Zargham, I. TArJounmlo/Trarsmo 14(4):280-289, 1974. From the Department uf Aneathesidogy, Albaf Einsteio College of Medicine of Yeshiva University, The Bronx, N. Y. , Heart irc op CORONARY BLOOD FLOW ASSESSMENT WITH XENON AND RUBIDIUM This paper presents a clinical review of the methods using sasXe and wRb for the determination of eotonary blood flow. Although coronary blood flow ha been measured in man fm over 25 years, an Ideal clinically applicable 32 93 TIFL 0305641 7 t,O;;0654 1 I
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PRIIY(IRAL INVESDCATOR OR INSTITU]7ON MICROBIOLOGICAL ASSOCIATES, INC.- Bethesde, Md. CHARLES MITTMAN, M.D., Dirrcror, Depornneel al Respiralory Di.senser, City of Hope Nalional Mediyl Cen- ler. Dnarte. Cal. GEORG B. NEURATH, PIr.D, Mirra- nnnlyriml Luhwmnry. Hamburp West C.ermany. ALBERT H. NIDEN. MD.. Pro/es.ar of Medicinr. Drew Posllraduate Medical Scbod and Uuivendy of Southern CaG/arnia; Chir/. Rrfmnnary Diuare Secnon, Martin Luther King Haspilal, Los Angeles. OAK RIDGE NATIONAL LABORA- TORY, Oak Ridgq Tenn. MALCOLM C. PIKE. Pu.D., Professur of Coaimonily Medicine and Prdi- auics. University of Srmthrrn Cahfor- nra Scbod of Medicine. Los Ankeles. PROCESS & INSTRUMENT CORPO- RATION, Brooklyn. N. Y, RONALD E. RASMUSSEN. PnD_ As- .,rmnr Re.aearcA Phpiulogirn, Univer- sity of California Cancer Research In- slilule, $an FDnciKo. T 00206'76 PROlRCP TyyLE Studies of in vivn chemical earcirbgene- s[s fmyrovemem and nandardistlion of tests for aeyk hydrnearbon hydroxylase in- drsdfon in human Ussues Developing mouse carcino4enesis, modrl ayslems for one in inbalatson sludks PRINCIPALINVPS77GATOR OR kNS11TUHON TIMOTIIY 1. REGAN, M.D, Prufrssnr of Med¢ine; Dfrtcrrn, Div/uou of Cardiovrrscvlor Diacarer, College of Medicine and Dentistry of New Jersey, Newark. DANIEL B. RIFKIN. Pn.D.. Maisnmr Pr.ufrssor ol ChemicM BfMngy, The Rockefeller Universily, New York. Study af earcinogens (MCA. DMBA, )OIIN A. ROSECRANS, Pn.D., Auocw Mo), cigarette snqke cnndemYtl and are P"fessor of Phnrrnaa+fogy. Medb condemale fradions by subeutanews ca11 College of Virginia. Richmond. and pulmonary inuoAsclian into mice Development of faciBlip for, and inilia- RONALD P. RUBIN, PxD., Asrodure lion of, a sndy of ehronie lohaxo ProJesear o1 P6amracoingy. Slale Uai- versrly of Ncw York Downxlale Medi- amoke Inldatioa in mouse slnim cal Cenler, Brooklyn. (Now Pro)esr.or with coMrasNng eusceptibllilim to car- of Pfmrnmcalosy, Medical College of crnogenmir Virginia- Richmond.) Heredimry, suseeqibili/y to bronehiis- UNA S. RYAN. JM.D.. Srafnr ,yckndsr, <mphysema Papanicolaou Cancer Research loslitu1e. Miami: Assismnl Proferaor of Medicine, Universily of Miami School ol Medieirx, Miami. Fla. Kinetics of nilrosamin[ fnsmalion in IP bncco smoke B. V. RAMA SASTRY. D.Sc., PH.D, F,Beqs of cigarette smoke. noxious tumea and drugs on the terminal airways The chemical, physical and operational characleriaalion of two types o/ do- virex for the generation and oubse- uenl exposure of anhnats to tresh y PruJes.ar oj Pharmarology. Vander- bill University School of Medicine, Nashville, Tenn. SCkIPPS CLINIC AND RESEARCH FOUNDATION, La Jolla. Cal. CARL C. SELTZER. Pn.D. Nanomry Rrreorch Associmq Peabody Hureum, Horvnrd Universily, Cambridge, Mos. LUCIO SEVERI- M.D, Oirrcror med PROJEa.T Ty1LE Variables agectinR the ceNiovascular ro sponses In chronic emokin{ Prolcases produced by mammalian Ihsue Slale dependenl propertiet of nicpHne- telared eompounds The aaion o/ nicotfne on the adrenal gland The role of endothetiN and epithelfJ cells in rao-ventilelory funetiom of thc /anka Influence of nicotine on the release of acelykholine in thc human placeMa and its implication on the ftlal growth Immunological toropelence of mouse strains in retalbn to chemical earcino- genesis ConstRulbnat sludies relative to smoking and coronary hearl diseasn Allempls to idenlify the viral agenl(s) cigarette nnnke Study of Ihe relationship between sol- Dmn. Irururde af Anoronry nnd Pathnl- U"y. Division of Cancer Research, versily ol Pemgia. Pemgia, Italy. respomible for shcep-lung arknomNo- sia and to tramfer abis neoplanie dis- nsa to rodenls mplibilily- to certain cancers and aryl hydracsrbun hydroxylase (AHH) ae- CHARLES B. SHAW. MD., Ch1eJ, Sec- Hydrocarbon membdiaing ensymes and livily rion nl Mr4imf Grnrrio, M. D. An- lung cancer dcrson Hospital ard Tumor Inslilusr, Prufesrcv of Rioingy, The University Comlru<lion of an experimenlai device of Teaos at Honnon, Houston. for monitored exyosure of amaB ea- Perimcnlal animals lo Inbacco smote SI OANF Pn NATHAN H D Prnfn- Effect of bcnm la1 pyrenc ard dcriva- rnhal.bon - . . . ., sor of Biochrmi.nry, iTe Universily Iives on mammalian lung cdls Modigcalion of Wallon smoking machine of Tenrrcssee Center for the HeJth in connection wilh a new prololype Sciencea- Memphis. SI OTKIN Ar- THEODORE A PN D Mamralion nf tTe adrenal medullae cam- Effect of cotxrcirrogens end lumoe pro- . . , . ., sirlnnr R,.lrunr of Plm rolnpY cholumine stores in normal and hyper- motnrr on DNA mpair in mamm.llan , Duke Univcrsity Medieal Center Dur- irnLve ralr cells msceplible to chemical Innsfor- mrtiun , ham,NC. 76 77 TIFL 0305663
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comparing the tlfects of chmnk make inhalnuon In two etrains of mice. SneJl'a and C57 Black, selacled for their respeclive tcndenoies with aging to derdnp spontaneous lung cancem arsd vascular alteratium in lung and hean plus lymphaid cell infiltrations around bronchioles and bronchi Only rarely do Snell's mice spontaneonsly develop such vascular lesions, while C57 Black mice do not develop sponranwus lung carsxrs. The hlter auain is aho espe- dally well known for its excellent immune response. The two mouse sypea indeed bad a notably different response to chronic smoke Inhalation. Afler mh.ling whole cigarette amoke and eepecially its gas vapor phax. Sndl's mice developed lung aderws'.arrinoma more frequcndy and earlier than the canVol animah, while the C57 Blacks did not. Tinse mice, however, had a higher incidence of vascular change in lung and hean after whole cigarette make lahalallon - and not afler Ihal of the gaa vapor phase - while sw such eHen wan noled in the Stsell's stnin. Jtesults suggeel that cigaretle unokc rnhances existing genetic sueceptibilities in Ihesc Mo slrains, but immunobgial pro- eesaea may play a rolr in theee diflernntial responsea as well. Chronic exposure m the gas v.pm phase decreased the sotai number of Immune competent eells per spleeo ia Sneirs mice and still more prolonged exposure to higher smoking levels lowered their mtibody-hinding capacity lo polyvinyl pysralidoac. These observafions mggesl that the presence of IympMid cell infiltrations in C57 Black mice may aller their lungs' response to cigarctte amoke. The relation- ship between lymphoryles and the frequency of spomaneous lumors in dilfer- em slralass of animals and their respomes to cigarette make merits further invetliPlion. Unchunbrrger. C. and Lcuchteaberger, R. Onsnlogy 29:122-138, 1974. . From the SWiss Inslilute for Experimenlal Cancer Research, Laus.nnq Swilzor- laod. THE EXPERIMENTAL EXPLORATION OF HEALTH DAMAGING FACiORSIN C(GARETTE SMOKE Allhough several studiea have wggeeted that cigarette smoking ie a health hazard, beog particularly Imponanl in the etiology of human lung cancer, it is preseaty dill dilheuR to delermine which speciBc make wusponents are swaiuus. The make reamns for Ibis uncertainty are thc large nnmber of smoke pomponen ing daa humsn asnoking habit in laboratory an:nals. Aceording to the amhms, however, dse available experimcnlal dala jusli/y the following conchulons: (1) Health damaging facmrs, such aa Nose contributing so carcinogenesis, am gound is both pnrsiwlate asd gas vapor phasca of cigarette rmoke. (2) Pdnling aaperiments in animals and exposure of cultures In the paniculale phase, ss,mely cigarette 'Yar." have shown that this fraction has carcinogenic properliea in akin. trachea esd 6rynx. (3) Inhalation experimenn in animals and eapaaure of animal and human lung cultures to fresh cigarette smokt have dmmmtraled esdsasscement of carcinogenesis rsol only after exposure to whole ?VO^'0647 lg cigar<ue make but also dler exposure to the gas vapor phase alone. (4) It is urgent lo characterize the responsible cumponenes in particulate and gas vapnr phasc and their meohanism of aclion. (5) The public should be informed that, based on preeent knowledge, cigarettes with either reduced "tar"or reduced gas vapor cronslituenu cannot he considered safe. Ilmt h, amoking Ihese does ssa diminele demage to heaith such as the risk of hmg cancer. Leushsenbergrr. C. and Lwchxnberger, R. Sozle!- und PruvrmivmediaW 19:41-45, 1974. Other fupporee A. S. F. C., Switzerland. From the Department of Experimental Cytochemislry, Swiss Institute for Experimental Cancer Reseatth, Lausanne, Switrerland. MODIFIERS OF CARCINs'X)ENESIS The envhunmenl usduubledly determines to some exlenl the'outcome of iWeracsfon bdween chemical carcinogens and cell comtituen/s. Any environ- snentA factor affecting th'u reactlon, therefore, is a modifier of the carcinogenic praroar, as am aome a[ the inlwroM properties of both carcinogesu and cell ceonimenu. While modfiers operase n of the moment of wolacl between oeR and carcissogen, Wey rnay in fact ha.e been ataive in conditioning one or the olher prior to contaal and urcinogenesh. EquaBy impomtn is the posai- bsTiry that modifias do nM aRaet the cardnogenic (xaccs, itself, but the devd- upmeol and growth of she resulting ncuplMm. Conss9u<nlly, numetoeu faelum aueh aa ooeucl.ogena, promden and inhibitara of caminogenesia, immuno- logic.al inhibiton rrf nmor grawds, vehicka and routea of tlminh(ration, and hap factora wn be owidered modifiezs, The arsthar9 objective in this lengthy revkw deding with AeMwl modigers Is to make those working toward 1he development of an effective syalem of cancer pmvemion Ihoroughty aware of Ihe available data. Ilq canprdreaaive duansfun preenb the variuus npeck of dse sub('ect usder fite main headlnp: (() Importance of Chemical CarNno- gesn for Man: (2) Binbgleal Modiflerr, (3) Physical Modiflnn of Carcmo- genesh; (4) Chemical Mssditkra: md (5) Discussion of Inhibitora of Cheusical Caminogegea's. Graphs and tables are sned whemver neeess.ry and a very bug bibliography s appemled. Hornburger, P. In: Homburgu, F. (ed.): TAa PhyibparAolugy, o/ Cancer: Biology and Bto- cAsmbtry. Baael: 5. Ksrger, 1974, vol- 1, pp. 110.154. Osfser wpporz: U. 5. P+bBc Health Service, Americao Canccr Sockty, Fannie E. Rippel Foundation, Virginia and D. K. Ludvig Foundation, and Blo-Reeearch Consuganlr; htc. From the Bio-Reseaseh Instilulee, Cambridge, Mam. 19 TIFL 0305634 I J
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EFFECf OF NICOTINE ON THE SWIMMING ENDURANCE OF RATS Swimming to exhaustion (forced swimming or swimming endurance), as determiaed by (heir inabiliry to surface after repeated atlesnpts, is a convenient method of exporiog laboratory animals to exetcise. It has been used extensive- ly to evduate the action and effectiveness of drugs on physical perfornunce. This sludy attempted to delermine Ihe effect of nicotine at various dose levels on the swimming endurance of raa In a walsr wb. In an attempt to gain in- sight into the mechanism by which nicotine agecls endurance of swimming rats. theinBuenee of various drugs (sedatives, anlideprettanla, central slimu- -~ants-)_OA_(ka1...a•ngn-~n rin.e b,.baced by nicotine waa examined also. Remlts showed that nicolirse, in all doses Injected. produced significant decreasa in the sw