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Effect of Smoking on Nonsmokers Hearing Before the Subcommittee on Tobacco of the Committee on Agriculture House of Representatives Ninety-Fifth Congress Second Session

Date: 07 Sep 1978
Length: 350 pages
03684330-03684679
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EFFECT OF SMOKING ON NONSMOKERS HEARING BEFORE'THE SUBCOMMITTEE ON TOBACCO OF THE COMMITTEE ON AGRICULTURE HOUSE OF' REPRESENTATIVES NINETY-FIFTH CONGRESS' SECOND SESSION SEPTEMBER 7, 1978 Serial No. 95-000 Printed for the use of the Committee onAgriculture U.S. GOVERNMENT PRINTING OFFICE 3i-121 © WASHINGTON : 1978 For sale by the Superintendent of Documente, U.S. Government Printing Office W ashington„ D. C: 204 02 Stock No. 052-070-04755-1
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® c 1 iP ;e n A0 ~-: COMMITTEE ON AGRICULTURE THOMAS S: FOLEY, Washington, Chairman W. R'. POAGE, Texas Vice Chairman E nE LA GARZA, Texas WALTER B. JONES;,North Carolina ED JONES; Tennessee DAW,SON D1ATH'IS, Georgia GEORGE~E: BROWN', JR., California DAVID R. BOWEN, Mississippi CHARLES ROSE, North Carolina JOHN BRECKINRIDGE, Kentucky FREDERICK W. RICHMOND, New York RICHARD NOLAN, '.Viin nesota JADfESWEAFER; Oregon ALVIN BALDUS, Wi'sconsim JOHN KREBS, Caiifornia TOM HARKIN, Iowa JACK HIGHTOWER, Texas BERKLEY BEDELL, Iowa. GLENN ENGLISH, Oklahoma FLOYD J. FITHIAN,,Indiana JOHN W. JENRE'rTE, JR., SouthiCarolina RAY THORNTON, Arkansas LEON E. PANETTA, California IKE SKELTON, Missouri JOSEPH S. AJSbiERJIAN„Pennsslvania JE'RRY HUCKABY, Louisiana DAN GLICK.IIAN, Kansas DANIEL K. AKAKA, Hawaii HAROLD L. VOLKMER, Missouri CHARLES WHITLEY, North Carolina TED RISEtiHOOV'ER„Okiahoma WILLIAM C. WAMPLER, Virginia Ranking Minority Member KEITH G. SEBELIUS; Kansas PAUL FINDLEY, Illinois CHARLES',THONE, Nebraska STEVEN',D. SYMMS, Idaho JAMES P. JOHNSON, Colorado EDWARD R. MADIGAN, Iilinoi's. MARGARET M. HECKLER, Massachusetts JA'MES M. JEFFORDS, Vermont RICHARD: KELLI; Florida CHARLES E. G'RASSLEY,,Iawa TOM HAGEDORN, Minnesota W. HENSON 1IOOR1•7„Louisiana E. THOMAS COLEMAN, Missouri RON \IARLENFnF., Montana PROFESSIONAL STAFF FOWLER C. WEST, ,$'taD''DireCtor ROBERT M. BoR, Counsel HYDE H. MURRAY, Counsel Jox,q,R: KRAMER, Special Counsel BERNARD BRE:v:vER; Preaa,Seeretary SUBCOStAfITTEE' ON TOBACCO WALTER'B: JONES, North Carolina, Chairman DAWSON MATHIS, Georgia WILLIAM C. WAMPLER, Virginia CHARLES ROSE, North Carolina KEITH G. SEBELIUS, Kansas JOHN BRECKINRIDGE, Kentucky JOHN W. JENRETTE, JR:,, South Carolina CHARLES WHITLEY, North Carolina
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CONTENTS ts STATEMENTS' Booker, Walter M.,, Ph: D., president, Dr. Walter M. Booker & Associates, Page Washington, D.C!----------------------------------------------- 64 Curriculum vitae---------------------------------------------- 337 Cohen, Reuben, president, Response Analysis Corp., Princeton, N.J'------ 69 Feinhandlor, Sherwin J., Ph. D.,, cultural anthropologist, director, Social Systems Analyst=.,, Watertown, Mass------------------------------ 56 Curriculum vit'ae---------------------------------------------- 331 Fisher, Edwin R., M.I):, director of laboratories, Shadyside Hospital, and professor of pathology, University of Pittsburgh School of Medicine,, Pittsburgh, Pa-------------------------------------------------- 2 Curriculum vitae----------------------------------------------- 232 Heimstra„Norman~W ., Ph. D., University of South Dakota------------- 21 Curriculum, vitae---------------------------------------------- 248 Jones, Hom Walter B., a Representative ini CongF~ess from the State of North Carolina-------------------------------------------------- 1 Knoebel, Suzanne B., M.D., Krannert professor, of medicine and assistant dean for researchy Indiana Unii-ersity School of Medicine, Ihxdianapolis, Ind------------------------------------------------------------ 49 CuiriculUm vitae---------------------------------------------- 322 Moser, Kenneth M., M.D., director, Pulmonary DiviGiony University Hospital, University of Californiay San Diego------------------------ 35 Curriculum vitae---------------------------------------------- 258 Salvaggio, John, E., Mi.D.,, Hendprson professor of, medicine, Department of Medicine, Tulane University School of Medicine,, New Orleans, La--- 46 Curriculum vitae---------------------------------------------- 298 Sterling,, Theodor D., professor, faculty of interdisciplinary studies at Simon Fraser University, Burnaby, British Columbia---------------- 41 Curriculum vitae---------------------------------------------- 282 CORRESPONDENCE Booker, Walter M., Ph. D., F.A.C!C., president,,Dr. Walter M. Booker & Associates, letter of July 26;1978---------------------------------- 79 Fisher, Edwin R., M.D., director of laboratories, Shadyside H'ospital, Pittsburgh, Pa., letter of: July 118, 1978'----------------------------- 78 Jones, Hon. Walter B., a: Representative in Congress from the State of Nbrth Carolina„letter of Aug. 1, 1978; to H'orace Kornegay, The Tobacco Institute, Inc., Washington, D.C---------------------------------- 7',5 Kornegay, H!orace R., president, The Tobacco Institute, Inc., letter of Aug. 3, 1978---------------------------------------------------- 77 r (IIr)
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IV STATEMENTS SUBMITTED Breckinridge, H'on. John B., a Representative in Congress fromi the State of Kentucky ---------------------------------------------------- Page 80 Farris, Jack Matthews, M.D., professor of surgery, University of Cali- fornia, San DiPgo. ----------------------------------------------- 119 Curriculumi vitae---------------------------------------------- 125 Fisher, H. Russell M.D., pathologist, Glendale, Calif------------------- 98 Hickey,,Richard f., research investigator, University of Pennsylvania----_ 133 Saunders, Louise Herou, president, Charlie's Cafe Ekceptionale,, Inc., Minneapolis,, Minn_---------------------------------------------- 136 Schrauzer, Gerhard N., PhL D., professor of chemistry, University of California; San Diegp-------------------------------------------- 139 Seltzer, Carl C., Harvard University------------------------------ --- 104 Curriculum vitae---------------------------------------------- 109 Stedman„RusselliL., biochemical consultant, Temple University---------- 82 St'atementsbefore Environmental Control Committee, Chicago, Ill.: Aviado, Domingo Mi., M.D., New Jersey College of, Medicine and Dentistry- 185 Ctrrricuium, vitae---------------------------------------------- 195 Langstony Hiram Thomas, M.D., Chicago Ill-------------------------- 158 Curriculum vitae----------------------------------------------- 173 Nylander, Lee R., Ph. D., vice president, Chemical Services for Polytechnic, Inc------------------------------------------------------------- 224 Curriculum vitae---------------------------------------------- 230 ADDITIONAL MATERIAL Cigarette Stnoking ani:1 Cholesterol Atherosclerosis of Rabbits, submitted by Edwin R. Fishery M.D---------------------------------------- 6 Influence of Nicotine on Experimental Atherosclerosis and Its Deter- minants, submitted by Edwin R. Fisher, M.D------------------------ 10
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80 age 119 12 5 I 98 ' 11133 i ~136' ~ 1~39 104 109 82 185 ,,195 158 173 224 I23o 6 101 EFFECT OF' SMOKIN!G ON' NONSIIIOKERS THURSDAY, SEPTEMBER 7, 1978 HousE OF REPREfiYNT ATIVES, SIIBCOai3rrrrF.F1 0~; TosACCO oF THE Co1SimPiTEE oY AGRICIIILTIIRE, Washin,qtanx D.G': The subcommittee met, pursuant to notice, at 9:30 a.m., in room 1302, Longworth House Office Building, Hon. Walter B. Jones of North Carolina (chairman of the subcommittee) presiding. Present: Representatives Mathis, Rose, Breckinridge, Jenrette, Whitleyy Wampler, and Sebelius. Also present : Representatives Fountain, Neal, Perkins, Nateher, and Hubbard. Staff present : Fowler C: West, staff director ; Christine Abram, clerk; Charlotte H. Far-well~ Carol A. Dubard,,and'Bernard Brenner. OPENING REMARKS OF HON. WALTER B. JONES, A REPRESENTA- TIVE IN CONGRESS FROM THE STATE OF NORTH CAROLINA Mr. JoxFs of North Carolina. The Subeommittee on Tobacco will come to order, please. I would like to announce to those of you who might not know that during the morning we will be interrupted by bells which means we will have to recess briefly to vote. We are going to attempt to do it in shifts so that the testimony will not be interrupted. We have schediiled' this hearing because of concern about an~ issue which is receiving a great deal of attention, that is, the effort to re strict smoking in public facilities. Bills are pending in both bodies dealing with this. Secretary Cal- ifano is talking about protecting what he calls "the rights of thee nonsmoking majority" while ignoring the rights of the some 60 mil- lion people who do smoke. Various agencies are looking into the mat- ter-for example, pending further action about smoking on aircraft by the Civil Aeronautics Boardl Some of the States and localities have adopted regulations to restrict smoking. That happened in Prince Geor,ges~ County, DTd.,recently. On, the other hand,, in the District of Columbia, the Councill voted d'own a similar proposition. For several years now there have been articles in medica.l journals on this subject, stories in thenewspapers, testimony before various judicial bodies, announcements by various voluntary health associa- tions, et cetera. For the benefit of the~ members,, I havequite a collhe- tion of these anti-items. We have built upquitea volume here. It lookss like public concern is growing on the question of whether tobaceo(i1)
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0 it ® M_ 12 a M In 0 0 M Cl a 0 2 smoke, such as that around the back of thisroom right now, is harmful to persons who do not choose to smoke. From the standpoint of this subcommittee, of course, tobacco leaf is a principal cash crop in~ the United States. A great deali of the eco- nomic data invol!ving this significant part of American agriculture can be found in the record of this committee as a result of the recent hearings we have conducted. Yet, no member of this subcommittee rv,ouldplacethe dollars and c,entsquestionsabovethequestion of health, whether the smokers' or nonsmokers'. I think all of us have heard,a great many negative speculations about this last point, and the, time has come to put some information from medical and scientific experts on the record to'help us in our own final j udgment. Accordingly, I corresponded with Drs. Fisher and Booker after hearing that the_~ -hadiapparent expertise in t.hismat,ter, and bothgen, tlemen ar,3 scheduled to testify this morning. Others who are present to be heard were identified by the doctors having studied this matter scientifieallyand they, too„will,be heard! I want to thank Horace Kornegay too for his response to my request for advice, and assistance in thisconnection. I think most of us~ recog- nize him as a man very knowledgeable in tobacco matters: tiVithout objection, we will see that the pertinent correspondence is included in the record. [The correspondence from Mr. Kornegay,, Dr: Fisher, and Dr. Booker may be found on pp. 77, 78, and 79.] Mr. JONES of North Carolina. The subcommittee is delighted to wel- come each of these persons who -will testifv as well as others, and weappreciatet.heirbeinri ablle to ac.cept our invitation. At this time I would like to introduce the members who are present. To my left is therankin.g, Republican member of' the Committee on Agriculture, the Honorable Billl Wampler from theS'ka.teofV'irginia. Tb my right is Congressman Charles «Zhitleyof North Carolina, a member of this subcommittee. To his right V is a member of the North Carolina~ delegation, t'~heHonorable L. H. Fountain. tiVitl, that, the. Chair is happy to recognize the first witness who is Dr. Edwin R. Fisher, director of laboratories, Shadyside Hospital. Pittsburgh, Pa. Dr. Fisher, we are happy to have yourhere. STATEMENT' OF EDWIN R. FISHER, M.D., DIRECTOR OF LABORA- TQRIES„ SHADYSIDE HOSPITAL, AND PROFESSOR OF PATHOLOGY, UNIVERSITY OF PITTSBURGH SCHOOL OF' MEDICINE,, PITTS- BURGH„ PA. Dr. FTS7IRR..Thanli yo11.,'M r. Cl1:IlrlnallL I am Dr. Edwin R. Fisl'a„r of Pa. I am currentlyy pro= fes.sor of t)ath0lo~nat the 1-ni<<l•iitv ~~fl'ittsburrlrSchool of ilfedi- cineand director of LIlwrntorir: at r!i,,~1i ysideHospital in Pitts- burgh, Pn. In udditinn. i,un n~Y n uln:,alt in !;ltlir,lo`N- at~ the Vete;rans' Adminr irtrntion 1T'ripital in T'ittI,nr_!1 :rn,l t1~r13'rownsville (7eneral Hos- pit~:Il of f:u„1.1 ]%tl; nraduateof theUniversitu of
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s I af CO- re nt e of ut m a1 `ter ~n- ent ter test og- is r.. el- We ~nt. on iia. 1, a the I ~ is fa1, A- _ Y, S- ro- tls- in- bs- of Pittsburgh~ Schooll of Medicine. I received postgraduate training at the Cleveland! Clinic, Cleveland, Ohio, and the National Institutes of Health, Bethesda, Md. I was certified by the American Board of Pathology in both ana- tomic and clinical patholbgyy in 1952. I am a member of the honorary medical society Alpha, Omega Alpha and Sigma,Xi, the honorary society for scientific advancement. I was the recipient of the Parke-Davis Award in Experimental Pathology in 1963' and the Man of the Year in Medicine in the city of Pit,tsburgh in 1966.. I am a memberof manyscientifie societies, including theAmericarr Association of Ciincer Research and the American Society for the Study of Arteriosclerosis. I am the.autlhorof150 scientific publications in American and in- ternational journals a;nd textbooks. Iha,oeserved on the editorial boards ofl the journall Cancer and of the American Journal of Clinical Pathology as well as t.heBoard of Sc'entific Directors of Ellis Fi'sche.l Chncer Hospital, Columbia, ]11o,, and the Board of Reviewers for t'lieAmerican Society of Athero- sclerosis and am the project pathologist for the National Surgical Adjuvant, Breast and Colon Projects oftheNlational Cancer Institute. I should fiistlliketo direct my remarks to personally conducted experiments concerning the possible atherogenic effects of nicotine per se. Atherogenesis is,the process which results in the disease which woconamonlv regard as hardeningof thearteries, technically called atherosclerosis. We have also conducted suchi experiments with actual cigarettiesmoke which, of' course, includes the relationship of carbon monoxide to the atherosclerotic process. Reprints have been made available to Yon describing these experiments. (See p. 6.)~ In these experiments it'was clearly,demonstrated in the rabbit that realistic doses of either nicotine or cigarettesmokef'ailed to initiate,, exacerbatle; or otherwise influence the atherogen2e process in that'species. Y'ott will notice that I used the designation "realisticdoses." I think that is eeryimportant. There have been some st'udieswhiclrhave exhib- ited minor orduestionable changeswiththe use of an eduivalent d'ose of 6Q.6~ or more cigarettes a da~~ in man. This is such ai large. number that I think man ~~ouldl find it~di'fltcult to findi tlhetime~to smolta~them. Another point which I would like to emphasize is this: One could justlysay you found nothnng in therabbit but can theesperiencein therabbite apply to man?' «'ell, we know that rabbit'shave their prob- lems and that man has, hisproblems. What the scientific etperiulentt in thelaboratorv can do is indicate.where we should look and perhaps «hat we should lbok for in the clinical se~tting. I'Vith t.hose: tn o pointsin mind, I should like to continue. It might be well toe-mphasieethat therei's nopharmacologic or other study of any scientific. validity oracccptability to mc~that indicates that nico- tine adrersely affec#s,coronarvblood flow. Indeed, most of the studies reveall that this agent actuallyaccentultes and enhances coronary blood flow. Accounts reliit-ing adv.erseefl'ects of cig nrettesmoke on angina, patients., that is, persons who:suffer chest pain, probably as a
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result of arteriosrlerotic heart disease, shouldl not beinterpreted ass indicating that cigarette smoke. i.s et'iologicallyy relatecl! to the arterio- sclerotic process. Again, one might note that this view is based upon studies that used! very, very small samples of angina patients-actualllp 10 or fewer pa- tients--which we would not accept as, a valid scientific example. Diy careful review of the literat'ure, confirming the conclusions based upon my own experiment~all data and the related work discussed, reveals a lack of scientific information which would allow me to con- clude that atmospheric tobacco smoke or its constituents represent a health hazard in nonsmokers. Notwithstanding the scientific facts,,there is a small group of'vocal nonsmokers who apparently have a special interest in trying to con- vincepeoplet,hat environmental tobacco smoke is harmful to their health. Although some nonsmokers are sincere in their belief that atinos- pheric tobacco smoke is harmful to the nonsmoker, their statements frequentlyy and, I might ad& , aLmost invariably lacka~ scientitic basis- a basis that would stand up under careful scientific scrutiny,. For example, at ai recent hearing before theN'ew Jersey Public Health Council on the t.opicof public smoking, bTs. Donna Shamp told' about her lawsuit against her employer in which she sought to preclude her co-workers fromi smoking in her presence, Ms. Shimp, who is not a doctor, testified t'hat she developed corneaI abrasions, as a result of exposure to tobacco smoke. She has a new etiological agent for corneal' abrasions. One might suggest that i f she had irritations to her cornea, the abrasions werethe-n factitiouslyinducedl Even some doctors make claims about atmospheric t'obaccosmokethat arenotsug ported' by scientific facts. At the same meeting of the New JerseyPukilic Health Council, Dr. La-ne,an allergist, seemed to attribute all of mankind's ills to cigarettesmoke, Hislist of maladies allegedlycaused' bytobacco, smoke ranged~ frorn headaches to arteriosclerosis. One might parentheticallyy note that it would bewond'erful if we could'say that tobacco smokeisthecauseofa]l of man's ills. I think this would make the scientists' jobandt'11ephysi'cians' job much easier. We know, however, that this is far from the. truth. fl, As an experimentali6t, or researcher, I have long been interested in, the etiology and pat~hogenesis of art'eriosclerosis in humans. As I noted previously, however, my own research an& review of the literature do not allow rne to,conclude,that smoking is the cause of arteriosclerosis even intliesmoker. Accordingly, it is impossible for me to understand how, on the basis of current information, a physician like Dr. Lane can conclude thatatmospherictobacco smoke causes arteriosclerosis in thee nonsmoker. Despite the lack of scientific proof, the sma]9 special interestgroup~ of nonsmokers continues in its efforts to restrict smoking in public. Take the situation of smoking on airplanes. Several years ago, the De-
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5 as pa_tment of Health, Educa.tion; and Welfare, in collaboration with rio- the Federal Aviation Administration, undertook a study of smoking aboardl aircraft. That study concluded that smoking did not present sed a heallthhazard to:thenonsmokers. Nevertheless, in, spite of't'hiscon-,Ipa- chision, the CAB has established smoking and nonsmoking sections aboard aircraft. And now the CAB is being urged to outlaw smoking a,sed altogether. ssed, IIowever„ as a frequent air traveler, I have observed that the vast oon~- magprity of a-irliiie passengers d'onot seem to be at all concerned with; nt a the smoking, going on~ in specially designated sections of the airplane. Indeed, one survey showed that airline passengers are bothered more ocal bycry,ing babies than by tobacco smoke in the cabim eon-One probleut that'we,face today is t.hat, reports of scientific studies flieir in theliterature and the lay press are often taken at face value by the public, and even sometimes by some members of the.medical profession. ;nos- I have already alluded to the results of studies, of 10 or fewer pa- tents tients. A recently reported study of 10, pa.tients with angina pectoris- tis- lrardlya scisntificor valid sample-ledthe author to conclude that atmospheric tobacco smoke aggravates the condition of persons with iblic preexisting heart clisease: This concRision, however, must be evaluated imp inlight of the fact t,hat t'heend' point of the.study,was highly subjec- t to tive,, that the stress factor was not controlled. ancll that % shamsmoke p, or other environmental impingement was not used. In other -,N,ords, not s aonlvwas,the samplesmall, but the scientific design was exceedingly ent poor. Yet', this work is frequently cited as one of t'~hebases for tlieelaimed hazard of smoke to nonsmokers. lthe Likewise, the few other studies that suggest a health hazard to the nonsmoker can, in my view; be rather readilydismissed for reasons of okeimproperexperimentaldesigni and'~lackofpracticaI significance.Ihavethealready. indicated to~you the studies which use unrealisticamount.softo ci~,rare-tte smoke. Thera are some studies in, which persons areplacedin ies rooms and the room is inundated with cigarettesmoke. These individu- to als~come out with all types of irritations. I submit to you, gent.lemerny that you could put some peopleini a room inund'ated' with rose petals we andltii-e woi>U all comeout with sometype of irrit-ation. ink In: summary, insofar as I am concerned, there is a lack of seientific ier. ini~orination incri'minating atmospheirictobacco smoke as a health hazard. This lack of information prompts me to conclude that the ihi proposals toplacere.strictionsupon t'he:useof tobacco in publicplaeested are at this time unjustifiecll dol I should like to close byy citing a«-ell~recogiiizecl cliche in scientific siscircles, Thecliche is,, °`In God .re trust, others must provide da.ta."nd What weneed is good scientifticdata bcforeIam willing to accept and ane submit to thepropositionthat smoking is a hazard tothe nonsmoker. is Thank youL FThe curriculhim vitae of Dr. Fi51ier may be found on p.232:] up Mr. JoNESof.YorthCarolina. Thanlk you. Dr. Fisher. lic. Without objec-tion; the material you rel'e«red to~will beinserted into e- the.record at this,point. [The material, referred to on p.6follbni-s:]
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s Cigarette Smoking and Cholesterol Atherosclerosis of Rabbits Edwin R Piaber, MD; Sfark Nholey, MD;.Rabert Shoemaker, MS', Exposun to smoke hem ena cigarett. per.day,ln'a slmulaeed amakftg maehim. for 11 to 1irnenths fa1lW laQUanlitahvsly Q qualltativNy' attsct atnsraaele.aata of aaRa and ex4amurall aa wNl aa I ntramural eoronary,arterias, vlaceraf:laslens, or sa- rum I('pids ef eholblercl:-fnd rabbls. SIm- Rxly: no dlMarencoa In Ihna paramotora wyre obsened.ln nonnoefselestaolemic rabblls sutiiected to "smoking^' aa ro pared to appreprtalso controla.. Smaking . alao fail'ay tD In1lWttca the appaaranca ol' Many epidemiologidal studies have disclosed an association be- tween cigacettesmoking (CS) ~ and morbidity and ffiortality.from arte- rioselerotic heart disease. (ASHD). This relationship appears lesss con- .immng than th~at'relatihg CS to res, piratorydisea,ses and aeausala role of CS to ASHD has.nat been eon,viadngly, demopatrated. Results of pliumacologic investigatiame-• con:- oeming the efiee6 of CS or nitrotine, the latter regarded as the cardio- .asntlAr effector of CS,',"• on the car- diovasc'ular..system have beencon- Ar¢pted far publioti'on .May 9..19]i Prrm tA. depanmenu ofpathctogy, (Dr., liahv and 6Ir. Shuemake.l and'~ndiuloyy (Dr. {vhdy). $hulY~ida Hmpjrtaiand'~tEe Unirenity et Pltubitr;h,(Dn. Fither-d Wholey). Plttr beeqi. Repr:nt:epuetbt to fineiwte, of'PSthalegy; 9hadp.idJ. Hupitai,: Snn Crnt.a. Ar., Pitta- eitr`lkPA'15= (Dr. Fuhey. CornnarY angiognarrta In rabbfta of gee eanoua groupa atudlid. Lunga frem only on. rabbtt swo/ectad lo. clgarett.smok'ing exhtbited rerslocPolmilld aypja al mueasal eplthelihm ef ma. Jorb'uonchl. Although :heseflndinga aro not necessarlly.appllcabla to those Ihat mlght oe ur In m varfhnleaa_ they, pravoke the need fore rtirfher Inquiry re•- gardlhg the eauaal~roh of clganette fmok-. Ing In tlfe developmentf of'ameroscleroVle hsart disease In .man. 8ictingand indeed!in some inatances eontradictory totb'e vieav reliting CS to. ASHD. . In a previous . studyper- formed'inour labo:ratory° it' was:ob- served.tliat the daily adrm:inisttation.of,ciieotine for three months failed to ~ quantitatively . orqmalitativeiyr affect atherosclerosis of the aorta, ectra- mural and intramural branches of the coronary, arteries, visceral lesions, or serum:lipidsin normotensive or hyr pertensive rabbits with andd without a dielaryy suppllment of cholesterol. The done of nicotine utilixe& was equivalent to that amount', absorbedi by m- stnoking approximatehy35ei:garettes per.day,The.purpose:of'the present'study was to investigatethepathologic et- tectsof"cisarette smoking"' on the razdiovasculac and other tiswesin rabbi ts as" revealed by coronarr angi- ography and apnropriatee histologicc techn.iques. Such studies,.as welt ass those ofsercm Jipids, tarrc pcrformed in untreated rabbits andthose sub- jected to hypercholesterolemia or in-d durrd atherosclerosis. Materfals and Mcthoda Forp'. two adulrmate and female alLino. nbbits, that imitiallyweigHed betwecn 7.6' and 2.okg; suncived or.s,-tcsfcdthc rc• qoiaemeans.e oL't}te.experimenl.Croup I mnsisted oFten a ls.that'~were.sub• jected'.to CS'ofane~ macigareote daily for siadaya per week. Fstimated o wcigha basis ome eigarette per-dayr in a ra bbit .is equiralknt tosmoking.30'cisxrcttcsper day id man.,TBey were maintAined on a standard la`oraturyration and:water adGbl Group ¢ consist.ed of:asimtil'ar nuenbcr that received tAe standard ratiun:to whieh. 2% choleaterol. was added.'. These anir..air were .placed'wi.thirc the smoking chamber, fon an equi:alcnt time to thosc in group 1 i except thaywere not esposed toC3. There were lY ani mzla in group.3 0at',.crcrc sub- jected to CS rs tho;ein.g.tnup.l. These. weremaintaimed om LSeratinn,comL.ini ma tholesttro). Ten rab~bits of group 4 rcceived thee ree lar ration without. eh'ole;terob Ttieae were placed aithint.he smoki.ng chamber but as with..tkose in gcoup2 weree nor-posed tcCS: All aairnalsvere kill'ed after 11 to. 13 months a! CS'~.r.dYor d:otrs;erd admimis- tration mr the SMam CS procMure A' smo:e.exposuue m..ehine (manufar: turedbyProcess and lrsttumenls. Corp,, under coners<t by the Couneil for Tbbacco Ps.earch; USS, fnc) was.utili:ed.to -puse LSe rahbiti to tobacce. smoke under cor.dii- tlons cnmparable to th'ose of',human imoke. •1a ArChi Pathiol/Vol 9B..Dec 1974 ClgarelleSmoking end Athero5clerosleJFiSher et a!.
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Onmed e sut or in- L~ albim ecn l.6 hc i c- 'oup 11 b~ r fur weig,ht, Ihhillis ts per Id on a eter ad snmlr'er s which tni~mals'bamh'er proup,l 'c 7T r e . u ~ Theu red Ctcrnl. , ok tlo 13 mnii- ulae- Corp, bac '7ose vr.dd- okc et al. ENect ef'Smoking" an Gholeslerol-Fed and Ndnchotest erol-Fed Rabba3 . Totall Gain BodY Chalest.rnl, Triaircnrides, Tatal Upids, Mrospheli'yids, f3{ipo- a-Ilpo. Group NA. Weiyht.9m. mq/f00m1' m9/IOOmI me/t0om/. me/IOOmI protei:n,•ti pmtein~".. t,S'mekennIl. 10. +1.5 35=f6 125=61i 255=53 95=61 ]5 65 2:Cholesterol an1Y. 10 +7.0 955~2311 35t~62 1ffi6=6a0 629=61d 90 10 3,:5moke and . Cholest<rol 12 . +11 1•195~363 3d0ciaT, f930G65a 6a5=1ua a5. 15 a, Connos- un[reated: . 10 +2.11 60=2a. 110c, ]0 1m190. 1as~•6 35 6e azpacuve.. Smoke wu prvduocdbypositi.e p.uf6ng (blowimg)' metered air through a hocrsnatallyy held cigarette enclosed in pl, ticrdome durioga timedisecood pu2 This'vaa.followed by aiSsecnd. hold pe- rial, for a total eepd.ure tiae of 1", seo- onds. Thiiwaa toll~owed by a 36semnd purgee perird to aweeprout the smoke and a19-second. rest period. Each dailiy sesvion of CSeon:isted of eight auch cycles. The ap- parstus was:calibnted so:that the avenga- puEf volume of smohe praduced Was 35 mL The smoke Iras pushed Intaa mnsttne Yolume (384 ml) omoke. expoeueech'amber. Uniformmizing waa achieved witha me- rhaniml m4zeo atta<hed to one of the ani- mat mae holder plAaes.:Sm+ok'e dilutione of approxi:ma6ely 1,11 were ach'iev ed with one vette being ;mokedl The animzls wereheld'. in cylindrical holden and breathed the exposure chamber contents with their eoues justinnide the ;moke chamber. The cigarettea employed wen reference re;earch ug•lrattes (1R3), (obtaiaedi from theTubamaand Heatth kesearch Inati. tute, Urviversity,of Rentucky, hexington, Ky),.Theamoke aailysiiof oimtine for this refereneecigaretw :eith.a 23 'mm butt lentrth as utilized;In th'e:e studies.{i 263'3 mg- Alll eigareltes were equilibrated tu a BUY,relativehumidity =t>wsphen 6yy plan- dg tLem unrvnppedinOo:a diyiceator mn- tainiog 75%WiW, glytero6'waeen aolutioa. Bixhemtml I re.actioos wen performed um amrtie bloodlobtained at time of'death atter an ueernight fast To+aV lipids,: tri- glyeerides,.tatal <holeaterol, pbospholipids and e- and'$llpapmteim were deter-ned ai described'~previously.^ Uoronary angiognphy, was perfor:ned by oth:eterixatlono{ the left temonUar- tery. Thecatbetenwa.tpnsi;ioned eixher sel4eti•vely in the left cornnary nrirtfice orat theraot of the aorta.atrlhe Idvei of'the.rnn onary, cuaps byy talevision fiuoraacapy. , In- jictions ofdiatrizante m~e+elti:mine (Reno. gra(fim 76) were delivered' bymanma!Ij•y mntcnlled:Now. AtJeut three.animala ie each group hsd su-ful'mronary angio• grams performed priort to death At neeropry the.degree ofeortic ath'- ercecleresia wae determined arbbtrarily by AncnPanioliVot 98,.Dec 1974 Fig 1. Sel«Gve lWcoronaryangio- gram ol rabbit fed cholesterol but not sub- )eCrad.lo amokimg.. AlFierasclerotic bead- ina.g ofiorcumflez.branch is Canspi0uous (arrows). oomputiAgg theaserage gndes ufatb- erosclerosia of boSb the thoracic andab- duminal lportions as desm'bed previously,A Blo 'csh of.lungs, h"-, sorta; incettise, panereas,spleen,kic4oeys,gonads,and![Sy, roid were.fixed irt.d% formaldebyde sol5- tioa. One m.threeblorka.obthekfcand rightt mrenaryurteries were ebtaiced within 2em ofthe mronary.erifi'ces.: Par- a1Hn section wcre pnpared in the usual msnner and stauned withhematezylan-eo- i Io addi'dion,, sections of mmnary ar- teries, heart and'aorta were seiined wioh thionine at'pH 4, f:1®,000 for ntim.tinn ofmetachrmmaain and the orceio. elutiea mechod..At least 12seetions of:lung fromeaeh animal.were st..ined aLso by.the PAS reietien. The sta.tistkal signifi®nce of dif- ferencea between grvups waa estimated by, the SCudent atesti Fig2:-Selective lart coronaryangld- gram ol,Gholeetenal-l5d rabait auaj¢cted to emoking.,Allhough most angicgrama In this group of nbbitswere c-parable to those inFig1, coronar+ea in this animal were indiStinguiShable.lrom those o6 no!- m«nolesesndamierabbmts w.im': and'witn- au1 smoking. Tnie Ynimal ean'ihin large GagonalI brand of Idtl main corwury.ar- te7 (arruw):. Results All animals e.zh'ibit8d~ modest weight gain during the ezperimental period (Tab'le).~ - - Tbta] serum lipid9,.cHolesterd, tri- glycerides, and lipaprotei6s were sig- nificantiy (p<.01) but wmpazably al- evated in animals of all groupsreceiving the clbolesteral diea.(Tabte). Coronary,angiography diselosed foci of atherosderotic beading and tsar- towing of oneormore coronary. ar- teries only in cholesterol-fed nb'bitS. (Fig 1)... The degree of change wasw unaHeeted!by CS and the coronary ar- Ciparene Smot.ng and Atmeroulerosia/FPSher et al. 419
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Flg 3-Schema0e oA aortlo amerescle- rosb in (A) cholesterd-fed snroking and nonsanoking rabbita; (8) non-amokirng ano amoking normoCRolsaterolaMC rabdtl. teriesof rabbits maintained on the atock ration withoot addedcholesterv6 that were subjected to.CS appeared unaltered being indastinguishablee from those of the sham CS memberas of group 4(Fig.2): Aortic atherosclerosis was noted only in rabbits receiving chdesterol. Cigarettesmoking had no qualitative. or qyantitativemacroscopical I e6fect on these lesions.(FPg 3). Similarly, no differences were encountered in, the histopathologi¢ appearance or degree of metachromasia intheatheroscte- rotic.lesions of aerta, romnary, or, uther arterinesio all chollsteroi-fed `1, 1 y, Fig 4.--tAn„Nistological 'appearanceof imltmal'cushiona In exvamunat tvaneh'~ ol ten Conanary artery of enotG-terol-/ed., smoking rabbiL This appearance 1s /ndlslinguishabte from tnat obaerved In nonsmnking, cnolcterol-'fed rabblts.. Rlghl- Normal strueture.or extrarn~uralcoronary,arteryeneounteredinnormochoealarolernic smokin~g anonon- smoking rabbits (orcein elaniu stain. X 100).. Flg 5.-Atypical'spithelial change accompanled ~by loss of cilia of bromchial epiehertum - encountere0 in normacholasterolemie rabbit subjected M1o smoking at IHO c^mpare0 to nermal mucosall epitheflum` at right (liernatoxy4incolin, x 250).: - rabbits regardless.of being subjected to CS ornot (Fig 4). No changes were noted in, these vesselsofrabbitss maintained on the regular ration th'at were subjectedtoCS...Nod qualitative or quantitative difference in lipig de- posits in theh'eart.orother viscera were evident between CS and non-CSS rabbits maintained on~.the cholesterol ration. Deposition of cholesterol was prononoced in the skin and eyes in a11 cholesterol fed animaLi, Fbcl of myoo- cardial necroses were also comparable in these groups.No increase in inci- dence of spontaneous medial lesions was enwuntered,ih any group. Sections of lunga showed only rarofoci of mild dysplasia of mumsal epi- thelial oe114 of major bronchi in onenb- bi~tmaintained on the regular ratianand'subjected to CS (group 1) (Fig5). This waaaccompauied by los3 of ailiaandabsence.of goble6 cells The re- maiuder of the bronchial tree in these and all other animala exhibited nor- maL appearine ciliated'mucosall epi- thelual cellls. No alveolar alterationswere encountered. .. Comment The results ofthesestudiesdad too disclose any substantial in&uence of CS on the severity, histopathologic, or angiographic deaturesof aurtas and' eoronaryy arteriess or serum lipids . of otherwise undreatedrabbitsor tAose subjectedto hypercholesterolemia, vis a vis atherosclerosie. These Andinbn 420 Arch PatnollVol.98„Oes t974OtgareneSmokiing amo'AmeroaclenasivFisner eE al
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9 ed ko nticn Ig 5). t cilia e re- these ed nor- .al epl- rations 6 fail to pence ofl Ilogi¢, orr rtas and lipidz of or those Emia, vis ~findings }re inaecord;with those of a previouss study recorded.b'yus in which nico- tineadEninistration alsoo failedito in- fluenes these varioos parameters in normo- and hypercholest rolemic.rab- Dits.'• Although sereral studies have claimed that nicotine may augment the athecoscletvtic processin this spe- eies'°^'it is noteworthy that the dlily dbse a6 this agent thaYwas: employed waa equivalent to approximately 1'65 to525 cigarettes per dayln man;; cer-tainlyan ezcessiveaad! unrealistic amount Further, only a "slightly" greatcrdegree ofatherosclerosis was noted in one study° whe.reas, othens cited subendothelial 8brosisu^ rather thanath'eromas asth'eresult of nicotine admia<istration. A high dbse ofnicotine as well as th'eadmin- istration of vitamin D mightarmuntfort the pronounced medlal effect on aorta and;coronary arteries norted :by . another groupof investigators,e' Serum lipidsth'at wereumaHectede by4S weregreatljr elevated in, cho- lesterol-fed rabbits.Absoliute.values in these animals that were subjected to the lipemic diet for 11 to 13 months, were no greater than in animals that we havestudied I previously^ receiv- ing thesame diet for a relatively sborter period such as three months. Therewgnition o6 the . more severe cholesterol deposition,in sucliaites u the eyes and particularlythe skin in the long term lipemic arvimals: than in those with lipemia ofshorter durationstrongly suggests that athresiuold level'of serum lipidsis reached after which such material . accumulates in the'tissues..This.possibility has.been alluded toby, Cunstantinides.'s Only, one (4.bA) of M rabbits sub-d jecteel to.(S developed focal.bronrhi- al mucosal change eharaoterized by s19ghE atypia of mucosal I epithelium. SuchchangeAas been observed with apparently more frequency ia ,human cigarettesmokess.P Whether such a pulmonary change would become more conspirtuous in rabbits subjected to CS for longer peririods remains to be demonstrated. The: results,of the present~ study, which fail to reveallanyadverse ef- fect of CS on th'esttvctulal integzity, of the~ tardiovascular system in the rabbit with,and without iadured ath- erosderosis, may not be appli¢able to . the .sltuatlon,{nnlan or other species. Nevertbeless,, theydo provokee the need for further investigation eon- cerning the.purported causal role of. CSinASHD. References LLanan PS„A..g I18, Sn+err. H: 7e6dao- r:,.per:we,r,t e.d'Ct;n:mr Sn~. Bammum, ww:me asxdktne ca 19sL 2 ltanhill S9J. 5.0.1 E4 geadl P. Cerdia e. W,tr rne2s el mld pre.:nr t<sta, ro-, beM na tllt: and enuking on smoken md nnmroukeR n+. aerr Sesso2ps,19se. s. Conman JD: Eemr o< p,nprenotd «t amd pruwra endrk/e Lo.. dwrieg ogaretm woldng. J CTi.. Pwrw.al 9]9-u-196A'. 4. Ar.e.,. w, Dendirg< J Iteka. 0: aeare rat. and eareee nona.el arr<r re,o« dn htgt,.b.-and.ooonmt,d<a¢arxusA.mdy, .,ale paweu .ic, aatie- peeer;a Aa. J,tr.r. Xrd "a49c-1e2, 191LA Tiamaa CB, e1 el Ob,enatie,n ee lbe Idd eidnal eeete of amoking un tlw blaod peusaR , beare u, ecmue selume, andadllc wlpntiu,. 6.alihr..yWngrdultt An. J.Lrw Md N874 as; t956. 6 Grrrigae B, J.in AC, Dnrla 1T. Th. dew4a- Inrr.t«poma w dgxta en.d13nget,.,c .nd after:ezadx A. J. Med ,Ri a.'[111719;196& T..Felt. LF, S.manek M, Asiedn DM: Cardio- ptdm.n.rr egem .r mbe<m, ana tewed >ud snnme 1L Cavnarr.ruw.r erceaa of agasew emokle end nimcne. A..d b^wet+b.. tLolt4 12~712-ns,19sa. i Pelikaa EW: Th. mesAadam of pnglfonfe blockedl pmddaM br,oimlina. A*. NYAcod Sri : a03L6p: 1960.>_. B,.n. Je: Aeudc ofn;mhne on m. Seaa Ave NY AmC Sd14ea: 14 Beu C, Bleaa 111, Tb. egaa of almtin. an dhemnn.rr erailionnuf dog> As tfmrt J ttxlos,'.1910, - 1L r,ra aA. sh-d TB: Aa.n of .Imen. aed'smokung oe mronen ci-a„t;on snd n+ro- eudia1:ocyg•m anf tioe A.. NYAevA &i pe:161-371, 1961 12'Leb G: et et ~TAe eRectef nimeine on en'er.i.. andwcal mmnary,bloodOer, ie the nnth u d dmea.a a g J rkn-s.v Tke t a>aIMn aa, 1970. 17 BaK Lpl laL.E.Re n.of, ogarttte smni g~ oblood n d ebd,r,n. G:r,.ra.mn ls :-,1-ti~. I9s1., e u I:ien Uaaek.r.v, sbe:..a Ta: Ani,,n os dgantm .meke .nareio.a,wl.r bem,ar- . ts Fed Pree 1a:317• 1957. 15. Btllet S. West ]W; CuMan SV: Graife enm a ia~.~.rnna,rr en,ena1 inleme,r of i c Anx NY Amd Sc, 9R159~.160, 19Fp.. n lb. Armnuge S1C. E(rec'.e of nim~u eed to- eano rmoke es Nond pceau.w aM'relesse af orecSal 'ea rn tb edreoal gl vda er Jleka. aml 29:51552b 1165. 17 L heal BIS Sch te CR; Emlq GS Tlw ml. of nn- u d.wminanrr oqamr. molung frwuexr .ab obx tians ete~r,in, r,rdioearadu enerr, an,e,;,t<d.;N,w. ae,mv d><sJeid a;. r~--.o+ n,.. sTaslse; 1967. 1a ls.ae PP, Band MJ: Bbod leeelr of Itne .ad pbYUdbgie eRaii .tter inb.latim of ' t.bea„:m.k. c.rJ P.S.-a e:Zs.ra3., lss9.'. 19. Firher r.B, n.wt<;n, IL' Wboloy a, et a Imwena.t nimcde en a:prri®e.•.a s>hem.ae- aodiu deserm;nmta And' Pacbt 96-~5 aW,~19TS 20.. Fisber E1L CteedD6, Baied W P: Er.aG ernnat!)9eramion on dnlutaml atAerwedeev.ia tn tAe nsbic L 8iswea:kolugia aea bior6emcaf aradie. La1 l.uLL 1211+a11. 1959. . aL.Stdanoeich V. e<al: Tbe ePfect of nimtlna w diet.ry,e S'emgena.u in nbbiuEryXd.c PaUu! 11'RAk.1969: a C=n +re-L3ea b A, D.e m grdra m Tn eres: of '..:a on T ~me de.a~ opmeut of r.L'erceditosu in nbbita Airw.fi+ri. Xarw Cer+e S41.dd.eki le:lbl+206, 1959. a[xllAnub y, et:ek Action rlJmNaue do la smtine sw l;mma aoruqne dn mpi,u.mauenn a•vn inbiblteve. ae un .srd... ()tA01 J Af.l.eorebr Jt a131 Sl2 19fi3 2l B G]L, 4nderbol' n' ' H eu AP. Prod eu'n otratan m tnenenoedi md tbeombo+reenei ath nimude .it.m+e D d dieurr rholnteroL A+n J 1tiLbo! 49:+J9-15g, 146a tl. FenaeliDG,.BeckloCGL: T3e e8ea of tvne en eal enmeeLl byp. amursrmletnia I, thie :raneil A,..Hw.,.m+ A.>ar sr: a13s a12195i ffi. W enml DC: Turva 3A; Yi l d: Ettert of aimUne en ctdetemt-,induead a~uerodeA.s io tlre nbbiG Cirt Ru 7256Pb1, 1959.. Zi. Wenul DG, ea eL Caedio.asalrr intc anida o<,ni®t ne" ergpne.;ee and hrpeed.el.. tetnlemia /d tae nbbit C:ic P- 9ti9i+f99,.196L Z& oomtaauniEea P: Fspr•+i-i Au- ero.e(..mv_ 4e..Yar1t Ue.ier.Cq 1965. a9. AuerMei O. Smo[',AP, Rnmmond JC,: et eL Cnaegh;nbmnretal api:b.iinm in ta.<;nn mdgereuu rmokieg and in relarian u Wng nvw- N 6npd J. Med :55253-257i 1961. Ianer, of al 1 Arcn f'allwl/WOt 98„Dec 1974 Cigarette Smoking and Atneroscbrosis/Fsher, et:at 421
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10 Influence of Nicotine on Experimental Atherosclerosis and Its Determinants Edu,in R. Fishe*, bfD; ReEerr Rothaerin..SfS; Afnrk N. tNhofey, S,(p; RieMrd Nelmn,,tfS,Rius6urgh A realilstio daily.pharmacolAgic dose of nicotiee. failed toqqantitawety or qualita- fiveh.aL"ect'athemselemsis at aarta and extramural as well as intramural coronary arterixs, wisceral lesions, pr seram lipids in nqrmotensive or hypertensive rabbitiwith and without distary cholester.ol I supple- mant. Na differenca in appearance of caro- nany.angiugrams ceald be appreciated inn niceeine-.trea:ed rab~bits witfi and wilhuud atheaosclaresis. This teehnique did reveal iess4ortueus toronaryarteriaa in hypenen, siven§Ei[s, which'was re(lemed nistoiwr cath/.bygraater lumiaal areas than in nor- motensive animals. Hypertension auyment- ad the ath'erosclemtic pnrcessin aorta and enronaryarteries ol . chaleslernl-ted nb- bids_ llitotine failed to influence induction . er maintanamee.ef renal hypartension: AI- L1ougt the clinical signi8canceaf thesa findinqs is cncertain, L7ey'pmvnke the eeed for further inquiry concerning the rols at aicotine in the..davelepmsnt of a0hero- sclerotic heart disease in man. 73lhem have been many epidemie- vlagical studies that shoo an as- sociatiorr.betbveen cigarettee smokieg (CS)and the mnrbidity and montalityfrom arteriosclerotic heart diseaseIeLsHlll: It is notexrorthp that th:ia relatioaship is less cvnspicuous thanan that for CS and disease.s of the respir- atory system. Further, a causal role of CS to AsHDD is lessclcar. Most antaeronists.to viewsrelating CS to AsI1D propose.a c'ornrttvn ~-netic fac- tor that may.berrsponsible ror both. Supin_'t forthis viesv appears.from IArpuL:~e~ewrnlur.u ll. tll3 .>p:.m~nxnrs and \~Lue and r..Jlnn~-,~Dr. Hu.pit, l.:,.nd ` ~il'il'.<I,v~;hrl)Aa..Fi.hcrandltiMl~:yLP,tl.- Iwrv<n K~-'• Nn.,L. tuln.tiuutn ofP,+ul.•lu~~,. ll~~.p~fnl, ?:W C.~ntn .iae. Yilt+- .~._~. the outstanding"tsvia studies'of Lundman' Some skepticism concern-g ing. the roleof CS in PSHD h'asd also been derived from the inconsistencies. and'somewhat paradozieal results' obtained fromepidemiological htud ies cons.ideringg the durati.on of CS and eventsoccurrin.g in ex-smoker; when compared to nonsmokingg popula- tions.'" Results of pharauacologic investiga- tions conoerni.ngtheefEect of~CS or nicotse onthe cardiovascular systemm often sho.r divergen6 results . whi¢hl , at'least im part„appe.ar, to.be related to,differeneesin.dosa,-e of'nieotinef utilized'and experimental techniess employed. Also,.most of thlese studies might be regarded as acvte amd there- fore unrevealing~.vith respeet to such a.chronicdisorder as AsHD. Never. theless, there is evidence irdicating thatthe cardiovascular effects of CS are.sytuonymous:with that of nim- tine-ir /n man, short-term studiess have disclosed'a slight pressore@acCr tachy-rardda and an.increase im cnr- diac output foilosving.inh'alation of cigarette smoke or intravenous injec- tions of'nicotin•,e."0 Although some." have found a morep;ol0nged pres,or effect and tachycardiaa in chronie smnkets than in nonsmokers fol'.o- ing.CS; otkenhare denied such dif- ferences'=O Studu"es ofCS or.nimtirte in animals rcvealicomparable.cardio- easculareN'ec-sl to thmseobsen'ed in, tnan andd are attFihuted to the sti.mu-g latingeffect of nicotine un tF.esympa-c thetic n u; system and.to care- cholamine rel@a•re."-' The net effect of theee actions ha,, . heen interpreted to repuesent an adver,e increa=ed oxy'gen demandb'y the hearti It li, notev.urthyi that dosea vPniiv'.tinef in dogs6 that a.ree apparently- de.uid of~ systemic effects not.only'reproducethese changes butalao resulfin in- creased coronary blood flo-" Tkias latter phenomenon appears to bee confirmed by. mosnrecent studies enn. . cerningthe.effects of nicotine or.CS on Rhe cardiovascular sys.tem.'+= Retrospective pathoioe c studies in man have7or the most partdisclAsed varying deo eesot increased aorticc and coronary atherosclerosis in heary. smorters (generally more than 20 icig- arettes. per day)ttian' in nonsmok- ers.- The. age ofmen exhibiting sudden death due to a fitst ep:isode.of AsHD has been found to be 16 yearsless ia heavy.y smokars than nonsmok- ers.and intermediate for ex-smoker and light' smokers~ Howerer, it sh'ould be indicated that mostoPthese studies failed to consider other deter- miiuants such as; serum lipids and hypertension, w4ich may, iinfluence the des'elopment' of AsHD.~ There have been surprisinglyy fesv experi- mrtntal studies croncerning the.eTeet' of CS or nicotine an the development of cardiovascular disease:="' The tesultss havee been conP'cting. and! analysisof their impor;ance is ham, pered, by differenees inspeciesn and techniques employed as well as rar}, ingdeses or nicotineedminutered.' Generally, the e~perimental designs have failed to consid8r other parame- tcrm that't erould infturnce or plap, a rule in atheevgenesia.. 'fh e puraorted i inporrance of eerum lipids in t)ie pathogenesi'.. of'ASfiD need;. no elatwration. The xlBec: of CS on this param:ter ha5 recciced a relo- tively. modest:t a .>unt of attertion.. Again, the results of im°esti^.ations in . this regard; aure inrorui:tentl, wmo ha- f.~hled to nntee any i rnediate etFects of CSin.man uppen srrum rho:- 2?9 ;,ic'. pathol,^!ol 96, No.v 1973 Nicotine & Atheiosc:ErosislFisher et at
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al i tr,;terol, ph'ospholipids;. or triglycer- ide+-'"•'r Free fattyecids appa.rentlyy increase after.. smokLngalthoui;h Finnkl et aN" believe this may repre- sent an ansietyreaction to thetestsbeingperformed., Although chmlester- ot may be unaltered after smoking; it iss claimed by, some,""' but not otheas; ° that habitual smokers ex- hibit higher levels of oholesteroland ,Q-lipoproteins than , nonsmokees. In animals, administrationn of nieotiae has been notedd to result'in an imme-diate.rise in serum triglyceridess but notcholesterul;tvhereas, t6econverse appears to obtain in morem chronic ezperiments?' A decreased rateof' cholesterol synttiesis as}vell as de- crcaseof'hepaticand rnyocardial cholesteroi content has been observed in nicotine-lreated! dogs.° AfesvA studies have b'eenperforn:ed concern- ingthe effect of CS adcoaa latios since alEeration of.thiesystem mayy also represenC another of the manyy fdccorsconcerned with atherogenesis. Generally, thereise little or no efCect on blbod coagulation in smokers or afterr smoB:ingr` although . increased platelett stickinessy and'd invitra thrombus formationi"e have been recorded. The purpose of this study wastoinvestigate, the pathoiogie e$'ects.oE nicotine, on c:.rdimvascular: andiother tissues in rabbitsas revcalcdby cnrn- naryy angiogaphyy andappropriatehistn6oo c; kistochemica.l and'ultra- structural technuques- Such ststdiesass well as tliose.of serum lipids wereperforaied in tmtreated rabbirtss and those: subjected too such determinants of.4sHD ~ as ~ h'ypercholesterolemia orr hypertens:ion,orboth. i+t a t e ri al s. an d'M e t h o ds Eighey.seven adultmale and femade alhi- rabhits we,ghing 2:0 to 25 kgsur- v ved.orsatisiB.ed the r qui of the ¢spenment. Thesee mmp;incd [Ns ~ follow- nupa Group 1 eonsi,ted ofl6'.that •i-d rnhbit chmrcontaining 2"rc.chp- Icatcrnl.. Geaup 2 mnsisted of ten that re i:,vd. the: n•:udnn ratim•.ifihwutmdaledl cheleetrmd b.ut w n>_t~'ven twiaedaily sul. inpeetinn.. of 0.5 mg rd,n d :.lidlin phiulAocsrlr P Inntie :ud[e led that P.I of nfav- u~ed a trveamuienrrise n6 IS w YO.mm IIp•^in htnod prv cndd tachycardia i nxnal Irahtiide. Thi~4wrd dailv.d~...e is ex- arch PatnolMol 96, Nov 1973 11 timatedun a weight:basis le hc equis•aicnl to.amokiagapp-imalely 35 cigurcltc-s par ddy in nsider g that t mg.of icrotinc isahsorhed frnmoneinhaicd ciga- eette.'rTher re 12 aniin.tlsim grow;+a, whr.e hyperteneiion was su s'uWyin duaed:by the metliod.of'Pave•r' cept that bheh unilateral: nephrectiimy. andl phagc enelnsure of the cantralateraI Ikid. ney,. re performed in . e stage.: Group 4 wnsisted of 12hypertensive rnbbits thax recei:ved nimtiete aa ddscrib'ed ahove- Gmup5waa mmprised of ten sholeeteml- fid hypertensive anitnaLs• and group,6, 15 aimilarly fed normotensive rabb:tsthat received nimtine as abo.-e.. Group Trond sisted of 12hyperteruive chelestervl-fed: atnitmalss that also received niwtine. Aaimals were killed 90.dayyfolloningoperation or the admi nuontiao of the diu• . Intenol diet or numtine injections Blood pressura was:estimated.indirectly at'biweekly iAtervalsb'y the sar capsu4e tech nique of Grant and Roohschild.'• AIC biachemicall reactions were performeden eortic blood'obtnined aathehmeofdeathaftler,anovern.ight,.ra-s! Total lipids w e.determined'by thephcsph-o m4lin rea 2- n;, Riglyr -des.b-v th'e au- temated calortmetridc pe -odnve reactien;, total ch'olesterel by the method of Li.cber- an arnd8urehard; and phosp5olipid; by y diRerentiacion...The. ,4-and n-lipoprotei.nswerecatcvl3ted as percent of lilpoproteins fiomm eeltufose acetate electrophor<c- ograms stained:with oil red 0 and total.l proteina by the biuret reseeioa Serunt t'al- cium, phasphorw, blood w nitroecn fHLiTry; hiliruh'in, udkaline phvsphatase;, lactic dehydmgenrne tLDHt: serum glu. umuc o.aluacetie txannaminase ISGOT),. and'aldcttvlytes by thee methods utilieedwith th'e'autoenalyzer": Coronary angi0grnphy, waa perforrnedby catheraneion of the lef[ femorai artery: Theeatheter waa positioned eitherselec- tivelY.in the I Rmmnutry orificc or at tlieront of the aorta at the.level of the aortie eunps by,television P.aaroscapy. Injectiooe ofdiaeriaoate meghuni.ne IRenogra'5n'61 was aavn.plished by.@ow-rate control at6 mVSec foratudaa a6 8'ml. Ininstamm of se:ective angia, ophy I ml was deli~ered h.m ualIwntrolladf'ox.fllms w expoaed'on arudl filns chaaoer,ararate of 4/see for twro seconds. At leasrfi- -i mais ach "-wp hadsua"sful coronar,-,:m-. gi.o/{rlrv perlbrme.l §uyt:priorto dt-uoh. At thee timeof'.dcath chehears, liver„ nd-cnal ^,1ands, andep(eerv .• ere dc-ed and ..r,;[hed. The de;- of aorti:c ar:.crt~- ac4,wie.d mined btrarily, b~oampueina th ,:e Iod. G athem- seh•~o sofbo~lt'thetl.torxeic.+nrl':[!wt,nmi-nil µrrtr~~ns aa ddscnbnl ipn.•vinii• IN ^ HI'ock, of hanrt, lirngs. x,rtn. small'in- testine; ppncreas, aplcen, kidncyv; l,•nnadi, and thynt&wcrchzcd In 4'+ formaldc-. hlydc solnCh,m Ilo>, neutnil. G.rmalincth'.we nf':id[c-i in both formaVdehydc- suiutim and Orth: f]uid. Onee to three. Elmksn('the Iift and riyhe cnrnnary.arte.ry eohtaincd- frow eoch ni4hin.2 cm of, themramary or;Fc- Thc .easdls in this locacion werefonthe mo.st part eatra[naral n position.:These were-0isectcd and one portioa was fnzed infermoldehydeso-iution and lheother in4% ;;4utoraldehyde for electron meroscopy. PanfOn, . aectioru re prepared inthe usual rnannenand .taiiud-ith hematnaylin<asin. In addi- tion,.section, orwromary arteries, hcart. andacrta w re stained with thiunine ®t pH 4, 1:10,U00 for esti.matiun of inetachro andlo-in elaativa and von.ICossa eaicium methode.. Adrenal glands te etained by theferrie-ferricyanidechro ma1[n tecbniquo. Portions of-ronary arv teriesfixed in glutaraldehydd w re.post. 5sed in LS oimium teuoxide, dah)JEated1 end embedded in resin t6fare;lAs, Ultra- th':in.sectionsfrn.m bothmranaoies inat', least fourani.maa in each group were ex- ami.ned by,an eVectten microscvpe.. Ttie1 l aalareaof: xtramuralb'canch- m pntedfrom similarlyma.-ited photo raphs of thesestnrcturei by the furmula A'-ab.. Compmisons o• suchmesturementsbetwcen: groups were e: pressed as r.rtios. The d:°•eren<es between g3oupa w.:u e> Hmaled Sy the Student / tent Results All animals gained weight duringg the ex~perimenthl period I•R•able. 11.! 'ITnis mas least promoumced in,Hyper- tensi4e members. YitpOine had no effect on body ~eighC . Blood pvessure uas comparablg (P > .05) '. but' signifncantty (P <.01) '. elevated in hypertensive animaLs:of all e owp.a..\icotine or hypercholes-a tervlemia or both',failedtoafLect tha level oFhype:tension (Table 10: Total serum lipida, total chnlescee- al, trigl}cerides„phosphotipids;.and12-11 poprutcins yeere signi hr ntly iP < .01).bub cempurati4y. (P> .05, eler•aL ed ih aninulsa all groupsreccivlhg thecholesterol diet. The adtnini_trn- tion, ofi r.~.utine or presenaee of'.h:, per tensinn or,burh hudd noetTecc on the-e aerum. lipi+~,. in. nonchol¢stnrol-fed vtimslsIP>.051. Total setvm ptn-, teins apfx•ared un- ,tered andi aiusular tn :rll grocp.IT~i+lr'_'I. No ch:mgcas in svrum c:trium,. pha plutorus. biliiubin- wnikcilinc NScoti:ne.6AtherosdernsisJFls^er et at 299
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12 r TaEle1.-Boa7 wfeigh't- Blood:Pressure-and Organ W'eignts of Chol¢sterol:Fed; Hypertensive, Nicotime-Trea{etl R30bits. CrwO CAanYein 6ne)t W'eiqhC A elcoaPressure..mmN: tInitial Finaf M'ear: Onqan t'rt~Znls•: Liver grrt ABrenslGlanls 1.cnolss;erol/eC1 •10. 96'_12 10c=10 56_8 95-30 1.010=21p 2.-mne .1.2 105_B 109+11 6.5_.9 104_20: .<90-.170 7, hyVertenvv> .:7 105.8 145 = l2' 8.8:_.i 99 _ 37 ~ .a9] _.2;0 4• hYcertensve.+Nitotine t.8 103 _ 7. 1<0- J. 8.6 e.B 90 z 30, .500-.130 5.nYDertensve+G+mresteeo1 a8 1o0~10 148=14 8.5c.6 100_.32 .983-.129 a cnaLesGeror.. Nicoane fi +9: 110 -7. 1M 11 6.0=.7. _25 105 .990 _.290 l;hrypertensrva+'CnDlescerol ..NiF,pcine ..7 105~10 138_B 8.8s:.7. 108_26 11P7=.320 Tab:le 2.-Serum Lipids:.Totali Pmtein in Cholesterol-F:ed, Hypertensive, aM MicpEine -Treated Raobits srDVV Total Lipd: nytao mt l rd3NesnCar m4t0o nt O6DMaeral my^0a mP. PntN, lipiES• my/'lo0 mr~ m tJDapreteiq. : TeLV enntestervt PnDteln, ' e.tije9rctein• : m; 1JenaCeY:erD4leG 2.d022500i 386=102 1:321-469 595-105 88: lE 2: nicatine. 314'- 74 95 t 209' 65 :20 154_ 80 45 ss 6.2 _.7 . 3.: hypenensive 320 _ 63 112~ 35 57._ 76 151 _ 75 55 45 6.6 _.7 4•arypertenyia. Nio:ine 320":65 78-20 110-40~ 132_6'a 50 50 6:5e:3 5•hYpentenfive+ . Chclssterul'. 2,3p8x3<0 335_110 1,200_320 773_120 85 15 b' ' 6.cndesterd« Nicc!irn 224a610 296e51 1.181:270 7a7_110~ 91' 9' 6.0_3 7, nypertenvve + GlDlef temL • Niccrine 2•652 - 710 420 _ 124 1,347'_ 420 BB5 x 98 88 12 &1 _:a Cont,rols 370-82 102:_ 30: 71_ 24 197 _ 66 phosphatase' were evident. Serum . lactio..dchydrogenase and''SGOT„al- th'ou;th greater than that ob'semed'in man, were in tha nomal mnge.lLDH, 175 to $50mi1Ci-units/ml, SGOT„7o . to 175 1 i Ili-units/mU for c0nurvl'.rabs bits in ail groups studied Serim elec- troIytes were comparable in a1ll groups, BUN was slightly but not signifieantlyelevated onlyin rab'hitss of group 3 that )trerem sutijented to the indiuctionofrenal hypectension_ Weight of the heart x•asgreater. IP<.011 in td:osegroups of animalss with hypertension; that of the adre- nal glands onlyin,those:groups.re• ceiving, thecHolesterud dietlP < .01)~ ITabla li., Coronary angiographyy disclosed foci of, atherosclervtie beading,.and nanzrvcin;:oF one or nwrc cu.ryn~aryartcrie.+y nnHin rholesterul-fed rab-hitA ~ Fig 1i and 21. Suefi ~ch.anges oc- r-,td. at varying sites ulune the., af= RrNd :vtory;md rrerr rtsost'frvyytent n tlre.c;umflc.r braneh,ofthe Iclt -~~th'atxppie:r.rcd: to be thc pre- d~ruinnnt've-el in therab'bltl Tlic nf cltan;;c:rplueurrd tob'e un.tF ic.-t~~l h~. thc ndminietrotien ofnic.+ tiim. lnrt ,•.i.: morn prvmnun¢edin thc hypert e n s i ve,. c ho l es t e ro L-fed a ni ma's Angiographically, coronariesi ofother?vise untreated hypertensive rabbitswe:re less tortuots dtan those of other groups:. Hype.rtensive;,cholestervl-fed: rab- bitsexhibited'moceextensive aortix atherosc!erosisthan normotetuic-e cholesterol-fed anitnals (Fig 3).' hico- tine administration failed too inAu-eocetfie severity of aortic atherosc!e: rosis. \oath:eroscletrosiaor other vascular ch'anges llrereobserc'ede in niaotine.tre¢ted or hypertensive and- malss not receiving th'ee cholesterol diet. The histopathologic appearances, degreeofela3tica alterotion, and inti- mal calcium deposition of theleeions oFtheaorta, mronary; and other ar- teries weree qualitatn-!y si:mi!hr in all'ch'olesterol-led rabbits revoadless of presence or ahsence of'.hy'per-en- sion or admini,tration of nicotine ard. ha%,e been rccountri itn.dctail.pre- viausly,°\Ietachrorrtasia appearcd increased'in aurtas fnlm nlA h_r-Percen- sive'rahbitswhethcr ur not the.-re- ceived th:eehule=th o!~diet:.In thc•v:e instances the metaeh'rotnatic mat^ri-:d w;u:esiden¢thnrugimut the cntiru medial coat as.well as in the intimal Irlsions o6 choleaterol-fed membets. .1a!ight',increase in metachror..asia+vaa appareiit in the media of the estra- mural branch'esof the coeonaryar- teriesof all hypertensive anitnal3 only, but thise char•ge was leas consiet. ent in other systemicarteriesof these animaLs No effect of nicotinee treatmenton the degree oPmetachro- masia wns apptecint_d. A qualitative diEference.in the t, pe of intiroal athetoselerosiss esisted between the lesiansof extramur31 . coronary anddisttibutino arterie; of simil9r size{600fr:to 1?OOµ lumical dismeter/'iFig<1 and tlie.intramwnl branchesof the coronatyv arteriass with Iuminol'di:aneter:of LQc to6i50µtFig cl. Ih.the former, the arttrro-matvus lesions tesembled thmee of the aorta xrith distinct fuamt411..; oun-- ing amoun6ss ofcollagen..and amor- phmns li.piddeposlts: t<here>; t!lu:e uf intramur.tl' b'ranches consi±trd. el- mo-t euhu- elp ofi"gie"Ihr!y shaped ucrtlular collatit ona'of opri- ea!h-clrar.lipidwith indi<tinct cell borde- : nndon!y ocr.t.'.orr:J nucleL. Th'is'Ic<inn nRen ap,pcand tD.o4+hrrr- atc the lumen_ Thc• ntcdi;t nf thltee 300•Ircl, pathol,:VOI i9fi, Ncv 1973 Nico:irne 3'Alt•.eroscterosis'Fisne^ et ~!
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13 0 0 Fl.g.. 1.-LeM1t. Ceranary angiogram of untreatld contrel n:vealing tilling of h:nt (R) 'anm lelt cerenanes FRI-I Ing el circumne. (076'ran¢h of ~IaY.er.'is greater Lhan th'at ¢I dncendimg IDI Yn~utary. Rignt, Angqg.ann f- Ayperlensive, cI+alK.er0ld/ed raEEil ra.ealing foci ot nLrowinj farmwsL in CPrcumllac prdmcn.~ \ Fiy2..-lbtt,selecti:va /efi:corana-ramgiugramid untreated, cemtrol: C, dreWnfles Crancn; o; descend;ng trltlutaty: Rignt. Angiognm orftper temslve. chaKterW-fed ra2bit.alscloses rocal narrowirg and;rregulariy. (srmwsl ¢f circumne.r and elscendidgfDl:orancltxs o/ lelt'.corenary. 1 \ tn! Archl Pa!not/Vol 96: No~ 1973 Nir,otene & Atf:er~sc;_ros~s:'F~ihe.~ et aL 7© t 34-121 0 - 78 - 2
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14 c(,~ FiQ3-Atnemsc4resis in aorta of;AtlwrmCtensive, ch0lesterohlfed ratoit5 wdn and+ah. ouP n.cotine aeminiatration:,(Bl.hypsrtensrv2.: cn'e!eae;:f.r..ed raeeits witn and ,rtnoun n,co-: tine:: an0 (C) ', n ncnoldsterol-Yed yntn~ nrpertenGOn arn icomne or ootn. F'g `. -Goss seenOns Or.eatramural brencM es of cO.cnartr xrtery from (len) :~wncnales[e~ok led, nicotinetrea:e0', r3b0iL (<enterlinonaro- Ititrcl-'e0, nyper,ensive rabbil~ (IJ,minal'anaa. is largerl. amd.IGg:ht) hypertemsixe: cholesta.vl. ted rattit revealln2 Inlimat evshnn end psaQua. ;ortein elastir~, x 621. 3o2:.r_- Novi973. iicvolved'. veseel3 wrass markedy, thinnedTheratioo6 theluminaa areaof ex.trnmuraf coro.nary,arter ies of h) perten;ive rab'bits to, that of; normaeensivc mernbcrs..vyq 1.5 to. 1.7whereas7 that'of other growps moreeloselyapprowinaated 1. The ultrastruct-ll features of cholesterol atheroma in coronary.ar- terfesnrere.comparab'le to,tkoaede-scribed previousl~y.iit aortas of choles- terol-fed rabbits by others.?""'\ico- tine or hypertension or both failed to infkuencethese changes.in cholester- ol-fed anis:alsor the normal app,ear- ance of these vessels in thoserece- ing2he oomuhalesterol diet. SectionsoF hemtt from, approxi- mat0ly one fourth of the rabbits from chmlesteroL-fedd gtoups.exh'ibitedmiI- iary.infarcts (Fig 6 and'7? orfoai:of subend'xardial necrosis in the my. ocardi.um of the left',veneriole: ln addi- tion, interstitial I infiltrates of Coam cells with or.vithout other-tnflamma-toryihfiltrate werealso observed in, one Courth ofcHolesterol-fed animal}. These appearedl tob'eo most pro- muneed in rabbits xith h) pertension and not7elaEed Ro.nicotin _treatment or levels of serum lipids: No distinct:qual itatire or,quantita~ ti've ditferencesa in lipiddeposits.ind oth'.er viscerawere.apparent in.any graup studied or.in the numbers.oE arteries in theminvolved with ather-. s omatous plaque., inchnle-acrn6-fcd rabGits.: \u diffcreruces in ferric-Gurri- cyani.de reactive chkomafiim tissue of adn`cnal medulla;,ras opparent in any group studied. Although the numbets oP,eachsesweresmall in eack group,.there.did not appear to bea.nyqualitati- orr quantitatlvediHerencesin the ath- eros:erosis,. angiooraphic,. orbio- chemical findine in.the male and female rabbits:.No increasein.inci+ denoeofe spontaneous medial 1 lesiona was encountered in any group. Commen:t The results of these studies fail to disclose any important iis2uer.ce of nicotine on these,erit}^e histopathol- ogia, uitrastruetural„ histoch'emical, or ang:o,-phkc feature; oCaortas and roronary arteries or serum lipids of other.vi;e untreated rabbits or those subjected tosuch determinants of athenxlerosis as hypecnhodestero- lemie orhypertension or both. Simi- larly, t4s incidence or se% 'erity of rnrc foci'of :n}ocardial necros:is n.as u1aL fectedl byy nicrotine administration. Theaemyocardiai changes have noc been observed svith any:dearee of ire- quency, incholesterol-fed rabbits nor receiving other thromb'og:en.ic factor,, b'ut was relativelyconapiacoua in this study.,OntheoRher hand, overt.my--ocardiul inFarction was not obaerved Nicotune 3.SlneMSt4ero~ri:Fl~stte& at 21
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15 Rq 5.-apid anhions occludln; lumena oe intrdmatr2f cCronary brar.ches oF cholefterod~ tad raab it(TematetyBntesin. original nnsyniti-: cation a 150N andenight be.explained by the pre- dbminant and ofte, exclusive.ih.- volvement of the ci rcumfleY branch of the, coronary system, a situation un- like that observed in max>_. The failure of niootine toauyment theathero.scleroticpracess even in cholesterel-fed kab'bits with hyperten-n sion isin agreement with results of provious studies inthe rat='and the dog,t'which fail to ascribe anypatho- logic changes in thecardiovase.ular system to nicntinc. It'should be noted'd that these species are quite resistant to atherosclerosis even.iiu the pres- ence of hypercholesterolemia. In the rabbit;,6Venzel et al,s-" us- ing gradedd doses of nicotine in drink- ihgwater, fai led'to discern any eTeet: of this agent on aortic ath'etoeclerosis: However,theydid'record "thickenin:g and fibrosis ih small Dranchesof coro- narie>' follo.ving nico5nea treatmenta!though detalsin thia regard were not presented: or depi¢ted.Further, ucclusive. corooary changes were en- countcred.innicotine-treated,choles- ternl-fed rabbits accompanied byy mcy:udiat necrosis.: Since this was nnt appnrent; in nimtir.etrcated anrhen. nntfedl chmlc•atei*d they, m.•la, crlth'attkeseeham;Ce•.vrredue. .~,-nnc Intora.ctinn.hctwcon tha:e ..,~,. ml:do thc,e auwhm.- r\'. ,,'m'd ..a. I-hility thut those ch.,n=,. .. ,-:d„eLtcSr,lc•,te-l,.-mu,nc 11, , ,,_!,,,n, hthi`..udy:5utu oitw ~~urm t hnit lhe refonnces lu uth',ro-. ~cld:r„nir. in.„Iv.,nu~nt i. cnncvned acn Pathot;VOl96. DLov 19:3 with intramural bnanches of the coro- nary arteries only. In addit'tcn, these investigatotsnoted that nimtinepro- dumd arise in chol4sterol in. malebut amt in female rabhitsi` whereas in our study.no serdi6erences were ob- sen•ed, aittiough the numbers of each were few. Stefanavieh etai=s found slightly greater aorti~c atheroaclerosis: and serum cholesterol inn nicotine, rrholesteroNfed rabbits.. However, these.investigatots did use.a duse of nicotine which, by, our estimates, appears to be equivalent toapprroxi- mately 175 cigaretess a dby in man or five fold tha6t used, in ~ these present studies. It:is of interest that they also ob~emed an.increase in serum phos- pHolipid9, which;,inouresperience with cholesterol atherosc!erosisinrabbits, is.attendantwitk a dectz:ued, severatyof thee vascular process.- The failureof nieotinee too influence aovtic aeid mucvpolysaccha,idecon- tent-is in ecc•ord with our histochemi- eaL findilngs in the nimtiiu-treated animals:.Inaeases in this moictyy have been noted1 in this andotl.ter studicsbyus in,situations is whiah the atherosclerotic p- in robhits is augmented.'•°•" The studies uf -Lxtto.ucti:eta1 "' ara Giifiriit tv. e..-:utu- ate s d e these invescigs:ors. utilix' .rquralcr,r .n of - n'ne• . focnd thiA sYn cit;nrettes,per uh-u.. .,,. ii..l gcr.t too induae an:rtic l fih,n.,i., thvt r.u anre'a:edto col::a- curnl-firdin„ butmind;clerl that pn.- dhredd b. :ulrra.,bnc:,nd •x.u IniuS'- i6ed'by monarmine oadase :inh iSi tnrs. This lesion isuniqueforwe have been unable to find any previouss or.sub~e- quent accounGs of a similar aortic change. Has;and- a:sociates" simi- Iarly: used an exceedinglyy highdose af nicotinee as well es vitaminI) in cholesterol-fed rabbits.Theyobser,ed a prvnounced medial er?ect on the aorta and other peripheral'.l arteries including thee croronaries, aswe]i as: intimal change includibg thromboses in these latter ressels.It is apparent that one of the major sources:of diver- genceof the.resultsof these studies from our findine may.reaide lnraely in e<perimental design, particularly that; con¢ernedd with the.duseof thenicntine utilired, whicA often.appeats to be in excess at that.which maybe regarded as realistic. It is of interesrth'at nBcntine failedd toaBeco theinductiom or mainta- nancee of 7enal hy-,, ertersion ~ in the rubbit- WenzeF and. Azmrch'r nntcdd sinulartesults on the inductibno- . renal hyperten;Ion inrnts. treatec!: with',nirotines but.asub'>eq•lent de- preasor- effrct afterI p ti- trcot- ment. Agaln the doarof nieutihe .e.., much erevter than [hat ux•dd in studi- It i. we11 r.co,~riz el ihat lo.r u,nosnf mcctine mac.ye dtirnu:L::im: ..whrr .'hecan.cr. . . aia, eghcr d,L.e n Thl<-tud -enlffrm . d;' ., ct rn hy r,erte : , n . n . , ., i- p -, r:,r:,,,::... Nvcotiurs atner-scier..,is ~Fisher et:ai 333 .
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16 Ree V.0 U §5 a ho7xrtensiec' abbita. not receiving [hr~ dtolcstorol dictt and! tFierofiro IavNiq~ achcrwehln;is. appeated Icc< turtuoas6y an,iugraPh)'• Thie wns r.•ftvatcd histologically by their sliqlydly, gg'cater: Iit'minalarual s.ug- geatin{; that urvcomplicated hvperten- Ston m3)'actYally' IltcTea9e COrUnaf)' blood.flna. The resul6a in the.puesent studyi, Vwhich fail,to reveal any adtl-ene:eBect of nicotine on the.structural intBgrity ofth'e cardiovascular eystem.in rab- bitss vrith or tvithowt sorne other deter- minantss of AsHD, Imapnot bee applitsble to the.situation in rian or other a{ucies. Nevertheles5, they:pro- voka.the need for further study.and sautinyy regardingg the putported causal :vle of CS or tucotine in?a?'}D. Thi. qudJ . w.wpppartd'bf: CruLL 6t9R1 frum the tl5 Oaurnl !or Tob.c<a Raxueh.. Refereaces l. Ltndm n T: Srnokinr, in relat n b mr.o nerytieerrt diJeoa+end Irhne tunaion:pn t.~rtu::A -nud audY: Atu bled Saaxd: Nppt d53,~pp.1-15;1966.. 2 Ru.nrk HI: Strea•: Iasuae.snd'ta.nna7 dixr.x m'orth Ammcarr pmleauwul rrr.upa JANA 19'!:69-19J:199:i: 3. Silti.rCC:. An, waluatien eC the eRe.t :of mul.inF on mmnarrl.eartdisen.e_JAdfA Tf11. t1~t3J:1946: l Seln-rCO:TheeB.taldtarel4enakinz rmrh heert dibe>se. ArcA E,avnn,HedrA YDJ {d-r~..19+'0.. S.Armiu,e Alt-ER nrni.atrr amd.tnb"c ann blaod. p{tvun .nd telaar- of ate- bnlam r- rmm the edrenal Clandi' B/ J PAon . d1 Si55R6 1985. 6.. t-hr GR SN er OR E le1 ~S:.The rv1. rA,nim.i e d[r..rmrmnt'of'.citarttu y(rtq "uencv 'ith ohxn ns d' <e.W:n cardinvsuular <ITeets naaoauoed .-i.th , tS'e tobaan..Ikalod C:in PM1armarol 7hrc e: . Ib9-iY6. 196T.. 7 luac Pe: Rand >tJ:i ebnd Ieveh or niovtineo andpS;.,okY~.e(-.+an- halrnnialtoGC-.. moSe. f.urJPAa•mc.v1d:169-!31::969.: m6' C.rRm.:n JI) Elhn or pmynnMol ln" blurd' dunn, aidareue emok- n. P/lormoav/9'JlJ4, 1909. ''J. .i:~n.w \t;, D;nd~n.r J. Rnkn.r SY:Ilean :,nJ,:r.6.n no ,.ide L-v.d:aner.n.,LnK hreh-: tr+...url nrn-r ea•vine avarc<r.m: A rtud~ .d. lun. nt- -th:ri'a pnWA...Ann /n- ~!In.r : t'6 . I9: I In Tx•m~.. l'tti, u.rh IM~tn.r:i~in+ m nco . h.li\~~Ii.rl .:L:St! N'rmrkrm;::en ILhludpnr,. I r -L I n ~J t- -y.rrln Ir,-.I Irl' n_ lult4 t lnnrr" 1/rr! 1..: _ ! 11_ ,1IL.rn„mf.-... .'.f.l]:.IiJT:Tie . . n_I,..~. m:..,`".u,.+nr..lrny nt r. r.:. ~ 304 Ar_H PStho{Mol 96. Nw 1973 12' I~tw,n P>. I ls,;: HIY.9:li.aa.. II,Td.,r,i.a Eynnmcn(d . d C(r•'•v/titudhx IU:Jinvrc••. tYVllion„ S.«'ill.i2.t'.~l'Mil. I::. 1lonnlrll «'J. sc,nl& : EI_ Kadi P. C'ar- dio.,cular,rtnJ~'Jo+ldyres Jl6headf up tiln. nrl,m+kin nnk.r nd n.u.mo. :~-29f.1 Ii"~: ~ -Oi. C~nr¢.i1; 91 tn It. Folla.LE'.Snmanek rl.A.rar1nD51t1ridi- opulmon- eRt.t. or tob.rno andrtla/edsWr.d cer: IL Comar. •'~+culnr e115- o( -'rette mnke and "i:IX- .; Arrh P.nriron He'a/tA. 1?T1?-'I16.1966.1SPelik'an E1P: The machaniem u[yanClim, ic bludade prnduced bj' vcx:me. Ann h')' Aied' Sh' 905'S fi9• 196d.: t6. BamJH: Action n! nieotine on tM heert; AhrtNY'AmdSai.903U.t3', t96u. 17' Rnaa C. Bleu bll: Tne ertece nr n'ri,r/ne an eh. mtvoar,. rinvld<ion ddMv Am HM J.' i9'.. 9&1VLa9"D.'1A l:iem GA, Sh'nrad TR: Action e( niwtim .nd anukihCon ~m.tonnry cirtulel'ma erd mr,. ec.rdiaL o,rpr. turhvuun. A"n A7 And Sei 90-..161'173,1960. 19 t<h,G,e[.I:Thee? tafnitvtineoneRec ti.a and torel tvronar,r binad Bor in,the anenhe-d tieedclos<dches: doE'. J~P1larmotd:andE:p . rherapruJ t,aalStJ~asao.; 1B.Tmn L)l. et LL ERcd'd djarette na on tononar:' bldod W.r and u.Iowrdra: neraboli.m- CerrJ"lion 16R 31-.b 7. l95'.. . R1..Kien GA, IsekYr \; Shbrnd TR. Aetion N daunue.mak. onnrdie.•mculer henWl'oam- in. Fd P.Q 16]1'-';195i. 22. B.Ilet S. R"eec J\Y, Gurma" SV: Cardiac etrat. of iner"mrronary', erterial. injrctiona o! nto pdne. An" NY Alad$~9D-: IMt60; I964i 93 StranCJPaaI:Onth.n.otlauianor<:[- a tne smokio' v ith corwur.-..od aort-ic athero- rclerwu JAtAervscle.!n.`u Rn. I030331'1, 1969.' tt SbrJ•ett Dd., et al Reloriun betv.e.n aortie .theraeektoaia and Yhe we pf a:nn<ue aod .6, mhaL NEe`I J]fed Zt9 ta13-tJ'!o. I96& 33. Averbad+ 0. ,Hvr.mond'EC, Gar6"keL I_ SmiinC ih nlatian to athanul:crosis of ihe wn- anarl anenos N Enz! J'a(ed PTJ:.775Tr9, 1965- R6 tYikna SL,P1air CSt Ci=orNrs amokine .rd .rteri :onck eo..is. Seienc.135:9'iW1;19Cv" 27. Spoin D. e! a1: 3ridden ddath due Ip mn> nutD atheroeclh.otic henrt dSeax:.l- >mnk- inC hbbit.. eod rec.nl thron'uuJA,Lt.A204:13J:1339:1969.'. 2Y Stefano.'tth )•. et alJThe edpet nf nitaino dietar. arhemgmnurnrabhrtv.Ezp bful.'e Pan!u! t 1.r13t,1969: , R9.. Cror),sLhwtm-idh A. Gonki; N; ICedn l1: Thr elhct nC "imtrneo vd eaReine nn the E/- reloP"'ena aE athrrn.cMroaie i" rabbin. A.rr UnwJlanar Cane Skradoa-ai t{a31208.. 19i9- 30. tenn hJ t 4, ch 'V'c d. l. ' ur l rnt ma aortipve d' un du lorrn tnflucr.e un Mibi nteue dela ryQrwrINAOr. JA:h; r.mlr. Rw•"x:F'I-3iIJ.nl9.i. 31. Hav G)l; Lend..rhulm «', Ilemmcne .l rrnducti:wr ar cakifnc.arA.mu.nennaclac.•r.•."nd' tb-- - -th n a miu D .ind' dietanrheldarcrvl. Am:J PaNrl,J9.:19-•.i'+, n:E SL: Th' _ LH (,T ' riae.p.i.nrny An" \'1 awW. cr Mt_ t~ -J•; tM+t.J3. tt' nn10)C.,6.xa:u'[:L~Thte1R Mnic•`r,perirmm~tul IM,yc4.karnJOrncr in thekrabMt: Am PAu•m A.wr.S•i[i~Ca~tl': 3k: S1. t1 I OC T / t L--J I}'Er•... .., ' . I .1 J .1 , h.ruclcn.~rr nrhenJJCC!e.lir, h'l:Ili: .,o. Dl.a.aht:rrd„+.+cutmm,rra. ..n nr n . rra Inthe ra/rMa~'C..irt ll.a 96'1iJi'rv., IxJ n Sn Knnni'.tw-n A: Ci¢amte.emrklri;;...d .e-.. rvmlipid.rn„wn~ OnAI'rd:ll.tll~.Ill6.. 196'!' 37 K<rsl.bhum A. BeIlrt S. Smrkin. +J a rar.. tor Inathlroa'lero.'u: A revew n.r.yiJnmioln,r... tali Pntibin_r.xl and eayenment>1 Jtud•.,. G:r. idrNr.21RI55.ITO11J55'. Ja. Frankl«',Friedm.n:R-SnIJfi1..l:.Cred:ac outpru. hXmd. prr.,um and rree r:ru ncid re- eP~rrras to ~nnkina in the nnnbea:rl.y;ate. An JNrdSCi25!:73Yii, 1966. a9.~&p'4 E, et aL SeNm: beta.h,prnteivnd'.elnlntenL in, eddttl menBe:nuwuhiy o, armkina, et and bdv, re:yA.c Cdnatner._+: teialt,I96S' 40.'F.nenen bl, et at.CiCe-te amok'ne chdot<mIJ b4od tre~sure und bal.' fat- nea.Obxrruipteln FiAlnnd. Loncee 1:J9'!-t9a- ts:,9 41 Pu.-rH;Rill mn..ID::E1".ecuremde-trtC nn pl•,cd<iott- uW lipd and h,roprnt.in le.ilr Iannt"/6D.131311 `l, t919 . 41- Aehesen R]1. Jes+np 1VJE: Tebs.iv+n~- ."d .erum lipds in old m..8A 31.d: °_ liOd~It11,196L. {3.'. CiJdblarnaron:S': EtTeetcCd'ronie nirn ad minietrauon ou cholere.ml mxabWu.n ur L- and brnn J. Phvnard £raThk~16'.i. T, eiSi. heart 1963 N.' :.FususedJF, Dturph. EA ES .n;..nnx- ina nnbbod cosCUlat ienard plelelK nurvi.el ta. mandr )red J 1:6n6xJ9;196'i.. ' ab. Ainbrua JL Mrnk 18: The e/fect oEdqa- wttf araekibC.un bkrod'coaqulaior. Ct-m Ph- aaaca(TAi/S:J_a.]l• 19L3. {6. E:+eerxrtH Cga.erre andtlne ntM the Iss vitro xhmmto.in orh- blocd. J-l•JA t9'3:: 1033-1D35;196i' it: O- S: SmnkinC erd isch'anri.-.heart dta- x..8r Hean J 3n1J5-156. 1963. ~a6. Pa~ Ifi; Sedmoi nah'n S1D. ]:lCvhbin J«:; Ob-tiona un th. roethod.. or producin- pen pSrie eaperimental hlyerteminri J'InbCt:' A7`d {6:91J!916, 1955 49 Gant :RT• Buch<hilid O Derice for eaa~ ninC binod pre.sure in th. rabhit_ J P6JS:dF' 61i26i ?63-1934. 60. . Flsher ER. Ceeed DL, Bai.SWF: EPea< a' nal h.perteruiaa:o"choleeteeolaohert•tclbcr n lhe rebbit. 1. Hiimpatholr~ie anlhiorhrn- tn;sudm.d . t.,t5 7a.eu :~^J' t-'_>:;, 195e' sl B.nd RC: The 6 ure nr h -. eedwh<Iiel lu.iuru . pe " ntal L eevl . ahervedemau or rabEiri Am J Pv bo! 3J:&9'., 910,t939.. 52. 3ull 1YJ5: \.rriort P!t CompnmN- marpimlo-ry nrtlu eer1Y atheroecletmt'rc I-cr- in.. roam. arvl dmlenenoL.nhemrclerorii i~ rhv nl bi4. en ekctron: nurrw.vpicuud;. J.iJAFeo• rdr R iJ:S-'t5ti 196:t. 51 L.~m E C.uny,rein the el..nmralateur.urtJ or the anrtn in hue,nn e'W eelzennae- nllm!k.,wcriroer. Li_ht and .-k.tion. m wty{e audler. .1lm Paehr..3firmb:W'8 Nypl:167. Cp I.B-'.:I Ww.. 51 F'-herES::(T IE,teml.atht*owh•m•r. , rabb s itharrhnixAmJP.whd.tuL::3'' 19tla. .-i i h .ER-ER :nrh-en: -S- kst mi n.hervxh+w n dr.iMie ..d.hie..l,.. Inn'N IrJ::61.}~ 1. 1!~•1:,, Fh ER. Sh. djt nlluerun , . ru I,irol.uter~ta he. 1 nws i!P _.. it' a Ch-II -- rwtrrnlnrntm.-:rndtN.bb.dpr.-.+ n."{,urr.:~ d: . I h P Jt.-rr....lhh (:' rh,rm...f-'rTF.rl Jb Ja.l'),n Yicotine & Ath'erosUerosiirFishar et al.l rel te: CC C~. ha
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17 E V. Vt a, Mr. JONES of North Carolina. At this time the Chair would like t.o recognize some of the subcommittee members who came in since your testimony began. We have Mr. Mathis of Georgia, Mr. Rose of North Carolina, Mr. Breckinridge of Kentucky, and Mr. Sebeiius of Kansas. Also, we are happy to welcome, two other gentlemen from Kentucky, Congressman Carl Yerkins and Congressman Bill Natcher. Are there any questions of Dr. Fisher? I do hope the members of the subcommittee can be brief because we have a number of witnesses. Mr. «"ampler. Mr. WariPLnr;. Thank you,, Mr. Chairmam I d'o: have one questiom Dr. Fisher, on page 3 of your statement, you refer to a Ms. Shimp wholestified that she developed corneal abrasions as a result of expo- sure to smoke. You testified that there is no scientific basis for Ms. Shimp's claim that she developedi corneal abrasions fromi tobacco smoke: Could you tell us what corneal' abrasions are and why they occur? Dr. FtsxEx. The most common cause of corneal: abrasion is a foreign bodyy in the eye. It is an ulceration or an abrasioni of the cornea-that part of the eye that covers the colored area. This is a very important part of the eye, obviously. Tobacco smoke in., excessive quantities might cause some people some irritation ofI the eye, but not corneal abrasions. Corneal abrasions caused by foreign bodies are unrelated to tobacco, smoke. I am talking about a particulate piece of matter. Secondly corneal abrasions ca.n be caused if you rub your eye excessively. Now, I don't know what her design was, and I have no reason to suspect any design on the part of' Ms: Shimp, but to me it would be a most unusual complication of the effects of cigarette smoke. Mr. WarirLEx. On page 4 of your statement, you refer to the study that was mad'e several years ago by the Department of Health, Edu- cation, and' Welfare in collaboration with the Federal Aviation Ad- ministration. They undertook to determine just how harmful smoking aboard commercial aircraft might be. I gather you thinktlieir action~ was rather precipitous when they segregated the aircraf'tt betweeni smoking and nonsmoking passengers. Let me ask youy in view of that, what would be your reaction to the requirement of having drinking and nondrinking sections on aircraft?' Would there be a correlation between the two or any scientific basis~ for that? Dr. Frsarrn. My reaction would be almost similar to that whiehI would give for smoking. I do agree, however, that some people for certain reasons seem to be annoyed when they arearoun& cigarette smoke. I sa,yannoyed because they are not subject to endangerrnent of their health, as far as I can determine: They become annoyedl and, of course, thecourteous thing andl the polite thing-andi I my self am, a cigarette smoker ifi I am around! people whoseemto: be annoy ed,I do not smoke. Thfisis nothing. This is jnstcommoncourtesy. Soi I' think perhaps there has been common courtesy demonstrated on tlheairplanes. Some people may not liketo~ be arormd people who drink. I think that is, a subjectivething. However, I do not thimkthereisany justi$cation, at the pres.enttime tosegregate the drinkers from the nondrinkers, although! one can seehoar this miglit;evolve,and theni we might think of a numl,er of ways that we could segre-gate.peopleon airplanes.
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18 © Mr. `VATNrPLEx. Then, from a scientific view, there, would be as much justification for being injurious to one'shealt'h to seb egatedri'nkers and nondrinkers as there would be smokers ~ and nonsmokers ? Dr. FrsxFx. At the present,time, I wouldlsay that is mvopinion;yes: Mr. WAMPLER. If we could carry this to its ridiculous aspect, if we had seg regation between drinkers and nondrinkers, smokers and nonsmokers, what is one to do if he is a smoker and a, nondrinker or a dMinker and a nonsmoker? He might have difficulties finding accom- modations on4heaircraft. Dr. FisiiER. He usually winds up as the pilot. [Laughter.] Mr. Wn.crnER. Thank y.ou, sir. Mr. JONES of North Carolina. 3fr. Mathis. Mr: M-,TTiis, Thank you, 117r. Chairman. Dr. Fisher, I have just one question. In your statement you refer several times to cigarette smokers and other times to atmospheric tobacco smoke. It is my und'erstandi'ng, that'the CAB' today is holding a hearing to decide the question of banning, pipe and tobacco smoking on commercial airlines. It looks like we may he in some trouble-those of us who oppose this kind of thing-with the CAB. Do~you have any definitivee evidence thatl there is a difference in theefi"ects of pipe:and cigar smoke vis-a-vis cigarette smoke in the atmosphere ? Dr. FrsxEx. Do you menn~ as opposed to cigarette smoke? Mr.MATHis. Yes. Dr. Frsfmx. No; I would say there isn't. Mr. MATirns.Do you think pipe and eigar smoke is comparable to: cigarette smoke?' Dr. FisziER. That is right'. The aroma; may be di'dl'erent. Mr. MaTHrs. 'So far as the harm that might occur?' Dr. FISIxER. That is correct. Mr. MnTxzs. Thank you. Mr. Jo`ES of North Carolina. The Chair is happy to recognize a guest, of the subcommittee, Congressman Steve Neal of Northi Carolina. Dr. Fisher, I have a question. Dr. I+IstiEx. Yes, si r. Mr. JiowFS of North Carolina. A number of reports sayt!hat tobacco smoke is a source of cancer-causing agents in the atmosphere. Have you reconciled those reports wit.h, your opinion that atmospheric tobacco smoke is not a health ha.zard ? That seems to be the gut issue. Dr. FisZ1ER: I am not prepared to accept this as an established dem- onstrated factl. You see, I think Ame.ricans are. in t.he. grip of a new disease, a very serious disease-two diseases, as a matter of fact-the manifestations are anxiety, fear, anger, rese.ntment, and panic. It af- fects the young. It affects the old. It affects male and female, tlhe.edu- cated, the not-so-educated. The disease I am referring to is usually transmitted by misdirected efforts,, the so-called consumeradvocates, certain books, newspaperhe.adlines; a.nd': so forth. Of course, the diseases Tam speaking of are smokeaphobia and can- ceraphobia. I think that if one were to accept these things at face value, it, would be very simple for t.hescientists-everybodyseems to know what causes everything today. It is totally untrue-totally untrue. I think there has been a great oversirnpli~ication of the com- m ve to ti•o ap in~ it : pe coi of arE 11 pos'. pu' Do I r An pul! coli sta; are int(I abl- if r an utai IistE Car:. you I) spe-~ Soc: c3iss, trou ingT caus «- and whio is nE have faul, and man
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~ nuch akers I ; yes. t, if and :er ocorrr- !s and nding~on of i looks ind of there rette ~ 1e to; ize a ,NN orth ; pbacco~ ve you bba.ccoa i i;I dem- a new a-t'he It af- te e.du- Isua11y ocates, rd can- rt face seems totally e com- 19 plpsitv of the scientific problems. The difiicult, staggering, devastat:- ing diseases are not, in myopinion, goingtobesolved by simple an- swers. They are complex or they would already have been solved'. Just to gliblyaccept that by smoking we are going to increase the at- mospheric carcinogens is hard' for me to swallow at present. It is not very palatable.. Mr. Jo-~ -ns of'Nort.hCarolina. Thank you,sir. Are there any othermembersofthe subcommittee whowoul& like to ask questions~?,17r. Rose. Mr. ROSE. Dr. Fisher, I am very interested in your statement and your testimony, especially the comments you just made about smoke- aphobia and canceraphobia. That rings verytmtet'o me. «'e are-latch- ing,on to the firstthingthat'appears as a cause of something t,hat it is not. But, as a broad proposition, it has been myy ea-perience that many people, such as yourself, in highly respected positions around the country, have,come up with some pretty sound opinions about the lack of proof that exists in this very emotional and very controversial area. People, like yourself, it, has been my experience, find it almost im- possibletoget'some major medical organizations or major medical publications in this.country to publish your findings and your results. Do you sharethat feeling? Dr: FISHEx: Very much so. Mr. RosE: W'hyhasn't the American Di~edic.al Associ'ationor the American Cancer Society.published, or presented', for the American public or for us in the Congress thepoint~ of vie« that y ou and' vour colleagues here today arepresent~ing?Iwish that -wecould somehow stage a showdown on this~ma.tter somewhere in a neutral foilim. We aregoing, to be accused, being ai tobacco subcommittee, of having an interest in promoting theuseof tobacco. Some of the press will prob- ably accuseus of tha'. I am not worried about that because I thinkt'hat if iveareinstrumental ini prese.ntingyour point of view and You have an .II.D. beside your name and that you worked' and earned the rep- utation that'you bring to: this, subcommittee,, people are going to listen to vou. Whydbn't the American Dledical Association and the Cancer Society publish theconflict'ingev idence that we have seen from youlhere today? Dr. Frsxna. That is a difficult question for met~o answer. I cannott speak for the American Dfedical! 4ssociation, or theAmerican, CancerSocietY_ I d'on't think thedifficallty resides entirel'y with them. The difisident' opinion-saying that cigarette smolte doesn't cause any trouble-is not as ne«swort]iy as reports that' cigarette smoke causes ingroavn t'oenails: or ci,~rarettesmoke causes cancer, or cigarette smoke causes headnches: Thatt is more affirmative. What. I think is needed at the present t'inaeis some equilibrium and a, careful look at the nroblem, and aar approach to theprobl'em which should beas scient~ificallvv imneccablleas possible. That is what is needed. We don'ti need emotionally charrred, issues, et cetera. We hare to reflect. It is not theA1L1's fiqu1t, and it'~ is notsomehody,else's fault. ~~'e just have to reflect on gettin~ back on center, so to speak. and attempt toreallvgo at these problcros in a very, ver}• scientific manner. ~
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20 Now, for some special interest group to seize upon somebody's studyy of 110 patients that hits the headlines. From the scientific standpoint',, that is setting us back. Maybe the reason we don't know about the converse is that there may not have been: studies which provide evidence. Theseare very difficult studies to design. What these people are saying is that their ammunition is proof. What I am saying, is that the ammunition they provide in defense of their position is totally inadequate. It is indeed totally inadequate. Mr. RosE: Thank you very much, Dr. Fisher and Mr. Chairmam Mr. JONES of North Carolina. Thank you. Do any other members of the subcommittee have any questions ? Would any of our guest's like to ask a question of Dr. Ffsher?' We are having a quorum call over on the House floor and we will recess for 5 minutes. Dr. FrsxEx. Thank you, Mr. Chairman. [Recess taken.] Mr. JoN-ES of North Carolina. The subcommittee will resume the hearings. At this time it is my pleasure to welcome to the witness tlable, Dr. Norman W. Heimstra, University of South Dakota Department of Psychology. Dr. Heimst.ra, we are delfighted to have you. Dr. HEI-NtsTRA. Thank you, Mr. Chairman. My name is Norman W. Heimstra. You! have a copy of my prepared statement. Mr. JoNES of North Carolina. Without objectiony your entire state- ment will be made a part of the.rec,ord at'this point. [The prepared'stat'ement submitted by Dr. Heimstra follbws:] greet vers: Profe Humar been agenc Seier, have Hum an Assoc the G I dir unit tory who a Ium V. activ: ment c
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!11 tie ~r. bf e- 21 STATEMENT OF NORMAN W. HEIMSTRA, Ph.D. The University of South Dakota Smoking Deprivation And Behavior My name is Norman W. Heimstra. L hav.eB.A. andiM.A. de- grees from the University of South Dakota and a Ph.D. from the Uni- versity of Rochester. I am presently Dean of the Graduate School,, Professor of Psychology, Director of Research and Director of the Human Factors Laboratory at the University of South,Dakota. I have been given research~grants for my work by a;number of granting agencies including the Department of the Army, Air Force Office of Scientific Research and the Council for Tobacco Research--Ui.S.A. I have been on the editorial board of Human Factors journal of the Human Factors Society and am a member of the American Psychological Association and other societies. In addition to my work as Dean of the Graduate Schooli and related Professorial work at the University,. I direct the Human Factors Laboratory which is an applied psychology unit which conducts research. At present the Human Factors Labora- tory consists of five Ph.D. level researchers, 10:graduate students who are working for Ph.D. degrees and a support staff. My curricu- lum vitae is attached to my written statement. We have seen in recent years a significant increase in activity on the part of anti-smoking groups to encourage the enact- ment of laws designed to restrict smoking behavior in public buildings
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2 0 and in the work place. The reasons for the sudden wide-spread and organized opposi',tion to smoking in publiic places are certainly not clear.. Regardless of the reasons, the result has been a surge of legisliative action which, in one form or another, is designed:to restrict smoking behavior. Sometimes restrictions which are sugges- ted or imposed do not have much impact while, in other cases, the possible implications of the restrictions are far-reaching. often, however, decisions to restrict smoking are based predominantly on information.and input from groups who feelivery strongly about the issue (and nearly always oppose smoking)' and who present data which, in their view, support their desire to restrict smoking in some fashion. Only rarely is there significant input,.based on hard data, fromigroups who oppose the restriction of smoking behavior or who could be considered as neutral. Recently, on August 22, 1977, however, this did occur when the Federal Aviation Administration denied a petition which had! sought to amend regulations to prohibit tobacco smoking on the flight deck and tobacco smoking by flight crew members for eight hours before commercial fliight operations. The petitioners had contended that tobacco smoking pre- sentedia hazard to airline pilots, primarily because of the claimed effects of carbon monoxide. The petitioners had also:asserted that nonsmoking,pilots were subjected to elevated carboxyhemogobl'im levels when other pilots smoked on the flight deck. The FAA looked to research conducted by Air Force scientists in recent years at Wri pos morn con- ~ the reqi , air< d'ecr to : conc adve repo Affe revi the that Yet, expe:. supp, . airl: pres< dete behaN react
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23 8 Wright-Patterson Air Force Base to heLp~answer the question of possible impairment in performance caused by exposure to carbon monoxide produced by burning,tobacco. In that study the scientists concluded--and I quote--"Carbommonoxide within the conditions of the experiments does not appear to impair the kinds of abilities required to perform space docking procedures, instrument landings of aircraft, or high speed automobile driving. Finally, no performance decrements were found in humans during the three hour exposure of 50 to 250 parts per million CO." The administrator denying the petition concluded that the unrealistic tests used to support a claim of adverse effects on nonsmokers involved "unreasonable"' comparisons. Tihere are important ihnplications in this decision. The report prepared by the petitioners entitled Smoking: LtsAdverse Affects On Airline Pilot Performance, represents a comprehensive review of the literature and a bringing together of virtually all of the data which, in the view of those preparing the report, indicated that smoking could have a negative effect on pilot performance. Yet,, when these data were subjected to careful scrutiny by neutral experts,, the conclusion was reached that the data did not, in fact, support the claim that "tobacco smoking presents a unique hazard for airline pilots that are incompatible with maximum,air safety" as presentediby the petitioners. Thus,, in the first major effort to~ determine whether smoking has an adverse effect on the wide-range behavior involvediin piloting an aircraft, the conclusion was reached that it did not.
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24 I was pleased with the conclusion reached by the scien- tists evaluating the petitiombefore the FAA, for over a year ago.I had pointed out that carbon monoxide--even when combined with high altitudes--did not have a detrimental effect on pilots' performance. I also made another point at that time, which was not necessary for the administrator to deal with in denying the petition. My point was that to keep pilots from smoking couldiresult in negative effects on their performance. Research in our laboratory has shown that involuntary smoking deprivation--teliling people they can't smoke--has behavioral consequences. While dhta are not available to specify accurately the exact consequences of smoking deprivation in the many situations in which it might occur, results obtained to date have suggested that when behavioral effects are observed they are negative or unde- sirable in nature. This has been true in studies we have conducted! dealing,with the effects of smoking,deprivation on psychomotor per- formance, risk-taking behavior and group problem solving. There are also effects observed on the affective or mental states (primarily, mood) of individuals. I.z. ~y S~. our research has indicated that in relatively complex psy- chomotor tasks, where an operator's work load is heavy, that not allowing smokers to smoke during,sustained operation ofl these tasks will result in poorer performance when compared to performance of
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25 B 0 smokers who smoke and to that of nonsmokers.- This tendency toward poorer performance is reflected'in several subtasks involvedlin the complex psychomotor task including both tracking and vigilance components. Analysis of the differences in performance between the groups shows that the poorer performance on the part of the deprived smokers begins almost at once and continues during the total period of:operation. Obviously, the performance decrement was caused by a psychological factor and not by physiological "withdrawal"' reaction of any kind. The time element was simply too short. It is probable that the poorer performance on the part of the deprived subjects is due to the fact that the subject views the enforced deprivation as a form of stress. The effects of smokimg,deprivation on risk-taking behavior are less obvious, probably because of the inherent difficulties in obtaining suitable performance measures for this type of behavior. The results of our study in this area are difficult to interpret and do not clearly indicate whether smoking,deprivation does, in fact, _ have an effect on risk-taking behavior, at least as measured by the tasks utilized. one of the tasks used in our study, called the "film passing" task involved having subjects make estimates of the last possible moment to pass a lead car and still avoid colliding with an oncoming vehiclie. This task was presented via 16mm color of actual highway scenes. It was instrumented in such a way that a
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26 V number of performance measures could:be obtained. In another task used in our study, a roadway was simulated on a computer-generated video display and subjects had to make a passing decision based on the speed of an oncoming vehicle. Again, a number of performance measures were obtained. However,, the results do suggest that there is an effect in that the deprived smokers appear to have less con- fidence in the judgments that they are required to make. In some risk-taking situations, this could have negative consequences. When the performance of deprived smokers in situations in- volving group problem solving was compared with that of smokers al- lowed to smoke and with nonsmokers, there were no significant dif- ferences between these conditions on the performance measures. In addition to performance measures, however, the behavior of these groups were video-taped as they performed on the group problem solving tasks and the behavior analyzed. It was found that smoking deprivation had an effect on the interpersonal behavior of individuals in the problem solving groups with the deprived smokers demonstrating significantly more acts categorized as "showing tension" than sub- jects in the other conditions. There is considerable evidence that smoking and smoking deprivation will modify the affective state of individuals, partic- ularly the affective state referred to as "mood". Dn,a number of
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I 0 r different studies, subjects complieted a Mood Adjective Check List (MACL) before and after exposure to a stressful task. The MACL des- .. cribes the subjects' current feelings in eight different mood factors or dimensions. Analysis of the pre- and post-test MACL's reveal'ed that subjects who smoked during their performance on these tasks tended to show much liess mood fluctuation or change than did the nonsmokers or the deprived smokers. These studies are significant because they offer some evidence, based on theorizing about the nature of "'good mental health," that smoking may, in fact, have positive effects on the mentalihealth of persons. The above studies deal primarily with the effects of smoking deprivation on behavior. Another important area of concern has to do with the effects of tobacco smoke on the behavior of non- smokers. We are just beginning to investigate this area. Based on our preliminary studies,, it wouldiappear that when individuals who have indicated that they are annoyed by cigarette smoke are in situations where they are engrossed with some task or are kept occupied, the potentiali annoyance value of tobacco smoke is reduced or eliminated'. Possiblie Effects of Smokin Deprivation in the Work Place There are numerous different types of work situatilons with different demands placed upon the indivi~duals involved. Predictions
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28' dealing with the effects of involuntary smoking deprivation on the behavior of these individuals would depend~upon a knowledge of the specific work situation. However, some general statements can be made. In most work situations, employers are concerned primarily with two factors--worker performance and worker moralie. Smoking,de- privation may have a negative effect omboth. We have shown in several studies that when mood is measured before and after subjects (smokers, nonsmokers, and deprivedismokers) "work" on a task, that the mood states of deprived smokers tend to show more change than those of persons who smoke during the perfor- mance of the task. one moodistate that frequently changes for de- prived smokers, by showing an increase, and does not change for smokers is the state that is liabeliedi"aggression". This is defined by adjectives on the MACL such as angry, defiant, and rebellious. it can probabliy be assumed that an angry'worker is not a particularly happy worker. While it might be argued that the presence of tobacco smoke in a work situation might have the same effect on nonsmokers,, i.e., make them angry, our data do not support this. In a recent study where nonsmokers performed in asituation where they were.not exposed to smokers and in a situation where they were exposed'to smokers, there were no significant mood changes in either case. In other words, in this study, exposure to smoke on the part of nonsmokers did not significantly alter their moodistate. I
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I i a 29 We also have data which indicate that deprived smokers, in group situations, will engage in more acts which might be classi- fied as showing tension or being unf'siend7y than smokers. Again, working in a situation with a higher level of tension andinegative interpersonal relationships could have an undesirable effect on morale. Based on our observations of a number of subjects in smoking deprivation studies, we know these individualis: (1) are often angry at the situation, (2), often wish to quit before complet- ing the task and, (3)I generally behave differently than smokers or nonsmokers. While we cannot state with certainty that smoking, deprivation would have a negative effect on morale, it probably would have. Another question, of course, is how much of a negative effect (on morale) smoking in the work place has on the nonsmokers. We have inadequate data to answer this question but the little data that do exist suggest there would be relatively little effect. The possible negative effects of smoking deprivation on psy,chornotor performance, which is involved~in many types of work situations„ have been discussed in considerable detail previously. We have found that smokimg,deprivation willi result i'n poorer perfor- mance on the part of deprived'smokers on several types of subtasks that are involved im many types of work situations. While the effects of this performance impairment in terms of production,. 34-121 0 - 78 - 3
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accidents,, etc., can only be estimat'ed, there undoubtedly are such consequences. When one considers possible effects on the morale of workers and on their performance, the total impact of' smoking deprivation in the work place may be considerable. It would seem~that decisions concerning restrictions in this area must be made with caution. This potential "cost" in terms of lower rrzoralie and poorer job per- f'orrmance of the deprived smoker against any "payoff" in terms of satisfying a very small but vocal!minority of anti-smokers who are actually seriously annoyed by smoking must be carefully weighed in arriving at a decision on the issue of smoking in the work place.
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I 31 Norman,W.. Heimstra, Ph.D. REFERENCES lers ;n 1. Arnold, J. L. and Heimstra, N. W. Effects of smoking depriva- tion on group problem~solving processes. Technical Report, Human Factors Laboratory„ The University of South Dakota, 1975. 2.. Arnold,. J. L. and!Heimstra,.NI.. W. Effects of smoking depriva- tion on risk-taking behavior. Technical Report, Human Factors Laboratory, The University of South Dakota, 1976. 3. Bales,. R. F. PersonalityandiIinterpersonal Behavior. New. York: Holit, Rinehart and Winston, 1970. 4. Bancroft,,N. R., Heimstra,.N~.. W. andiWarner, H. D. Relation- ship between smoking, psychomotor.performance, and stress. Technicali Report,Human.Factors Laboratory, The University of South Dakota,, 1967. 5. BergmanyH. L. and Pearson, R. G.. Development.of a noise annoyance sensitivity scale. Report No. NASA CR-1954, National Aeronautical and Space Administration, Langley Research Center, Virginia,, 1972. 6. Cattell,. R. B. Personali~tyand Mood by Questionnaire. San. Franciscoc Jossey-Bass Pub1'ishers, 1973. 7. DeKock,,A. R. Relationship between decision making under con- ditions of risk and selected psychological tests. Technical Report, Human Factors Laboratory, The University of South Dakota, August, 1968. 8. E1lingstad, V. S., Struckman, D. L. and Sebring, F. U. Abbott- 35616 (Tranxene)~ developmental study: Simulated auto driving. Technical Report, Human Factors Laboratory,.The Universi~tyof South Dakota, 1972. 9. Elilingstad,. V. S.,Struckm.an, D. L. and McFarling!,,L. H. A comparison of marijuana and alicohol effects on decision making performance. Technical Report,. Human Factors Laboratory, Tihe University of South Dakota, 1973. 10. Ellingstad, V. S. and Heimstra, N. W. Methods in the Study of Human Behavior. Monterey: Brooks/Cole Pub. Co., 1974.
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32 Norman W. Heimstra, Ph.D. 11. Glass, D. C. andiSinger, J. E. Urban Stress. New York: Aca- demic Press, 1972. 12.. Heimstra, N. W., Bancroft,.N1.. R. and!DeKock, A. R.. Effects of smoking uponisustai,nedd performaneee in a simulated drivi~ng.task. In H'. B. Murphy, ($d). The effects of smoking on the central nervous: system. Ann~. N. Y. Acad. Sci..,, 1967. 13. Heimstra, N. W. Effects of' "stress fatigue" on performance in a simulated driving situation. Ergonomies,, 197.0y 13, 209~-218.. 14'_ Heimstra, N. W. and. Ellingstad,. V. S. Humam Behavi~or:ASystemsApproach. Monterey: Brooks/Cole Pub. Co., 1972'. _ 15. Heimstray N. W. The effects of smoking on mood change. In W. L. Dunn (Ed.), Smoking Behavi~or:Motives and.Incentives. Wash, ington,, D.C.: V. H. Winstom.6 Sons, 1'973. 16. Izard, C. E., Wehmer, G. M,, Livsey,, W,. J. and Jennings,. J.. R. Affect,, awareness, and performance. In S. S. Tiomkins and C. E. Izard (Eds), Affect„ Cognition, and Personality. New York: Springer, 1965. 17. Loomis,, T. A. and West,, T. C. The influence of alcohol on automobile driving ability. Quart. J. Stud. Alcohol, 1958a, 19,, 30-46. 18. Loombs,, T. A. and West, T. C'. Comparative sedative effects of a barbiturate and some tranzuilizer drugs on,normal subjects. J. Pharmaco L Exp. Therapeutics, 1958b, 122, 525-531. 19. Lucas, R'. L., Heimstra,, NI. W'. andSpiegel,.D~ K. Part-task simulation training of a driver's passing,judgments. Human Factors, 1973, 15, 269-274. 0 20. Nowlis, V. and Nowl~is, H. The description and analysis of mood. Ann. N!. Y. Acad. Scil., 11956, , 65,, 345-355. 21. Marquis, D. G.,, Kelily, E. L., Miller, J. C., Gerard, R. W. and Rapoport, A. Experimental studies of behavioral effects of meprobamate on normal subjects. Ann. N. Y. Acad. Med.,, 1957',. 67, 701i-710. - - - - I Norm, 22. 23. 24. 25.
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H 33 i'- yf 22. 23'. 6 . k I I 24 in B. k.ems . 5 . W. 1'of Norman W. Heimstra,. Ph.D. Nowl'is, V. Research with the mood adjective check list. In S. S. Tomkins and.C.. E. Izard (Eds) Affect,.Cognition,and PersonaLit y. New York: Springer, 11965. Schori, T'. R. and Jones,, B. W. The effect of smoking on risk- taking inia simulated passing task. Human Factors, 1977, 19, 37-45. Stone, L. W. and Ellingstad, V. S. Validation of a laboratory procedure for simulating critical interval overtlaking, Human Factors, 1975, 17,, 24:3, 247. Tomkihs, S. S. Affect, Imagery, Consciousness Vol. 1. The. Positive Affects. New York: Springer, 11962.
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34 [The curriculum vitae of Dr. Heimstra may be found on p. 248.] Mr. JorES of North Carolina. Thank you. Dr. Heimstra. Are there any questions by subcommittee members ? Mr. Wampler. Mr. WAMPLER. Thank you, Mr. Chairman. Dr. Heimstra, in your statement you indicated that your studies mayy offer some evidence that smoking may have positive mental health effects. Would you elaborate on that,statement, please?' Dr. HEIMSTRA. Yes. I think that in general t'erms we do have data now that would suggest that smoking does enable a person to cope moree successfully with stressful situations. Mr. WaMPLER. During the recent recess of the Congress, I had the. opportunity to visit a number of industrial plants in my district. As a sidelight, I was interested in the number of plants which permitted employees to smoke during the production cycle of the day. In~ talking to many plant rnanagers, I think there is strong evidence to suggestt'hat those who are smokers and who are permitted to smoke during the production portions of their duties are more productive. Also,, the evidence suggests that you don't have the negative behavioral pattern that perhaps; as, youi referred to earlier, you might have when people are denied the right to smoke or are permitted to smoke under ex- tremely controlled conditions. Some months ago I was privileged to visit one of the large manufac- turing facilities in my State, Philip Morris, in Richmond. They also have ext'ensiveresearch facilities there in which they are studying all aspects of'tobacco; Apparently they are devoting a good deal of time and attention and resources to studying the very thing that you are talking about, the behavioral patterns in smoking. ~ The point I am trying to make is while the right to smoke or not to smoke, I think is a right, and! it shouldn't be infringe4 upon by G'overn ment or regulatory authorities, the point is that sometimes those who ~ in good conscience feel that denying people the right to smoke is the proper thing to do, it might be counterproductive to those who want to smoke. Is that a fair analogy ? Dr. HnrtiLSTRn. I think so. Mr. WAMPLER. You~ heard the testimony of Dr. Fisher who stated that in his scientific judgment, there was no scientific basis for segre- gating an aircraft or any, public facilityy into nonsmoking and smoking on the basis of possible inj ury to one's health from atmospheric breath- ing of tobacco smoke. `'Vouldlyou concur in that judgment? Dr. HFtr-NssTEN. I would hesitate to say. I am not a medical specialist, sir. I really don't have,that data. Mr. WAMPLER. Thank you, sir. Thank you,,Mr. Chairman. Mr. JoNnsofN'orth Carolinai. Thank you, Mr. W'ampler. Are there any other questionsfrommembersof the subcommittee ? The Chair is happy at this point to recognize Congressman Jenrette of South Carolina, a member of this suhcommitteeand another guest. Congressman Carroll Hubbard of Kentuchy. Our next witness is Dr. Kenneth Moser, professor of medicine, di':- rector of the pulmonary division, University Hospital, University of California in San Diego. Dr. Moser, wearedelight'ed to have you. STATE NAR FOR Dr. : My directc versit3, pulmo as a cl Healtll I rc. Medic, . affiliat Washi the hc period cal Re Agenc. Hospi I ar can C sional heart Soeiei Lung, Boarc Ih withboa.rd Myfi I a do nc tutes testif My tient tremc and t ordei As each resea fied I ousi the il In havi( infor a res chan gath give] 0
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35 [es may i health 7e data le more iad the ;t. As a ,mitted talking suggest during [so, the )attern people 3er ex- mufac- ~y also ing all p and ,, the not too vern~ e who I is the ant to ' stated segre- noking >reat!h- cial7st, iittee ?' 'nret!te guestl, ne, di- 3ity of STATEMENT OF KENNETH M. MOSER, M.D., DIRECTOR, PULMO- NARY DIVISION, UNIVERSITY HOSPITALj, UNIVERSITY OF' CALI- FORNIA AT SAN DIEGO Dr. MOSER. Thank youy 'Mr. ChairmanL lIy name is Dr. Kenneth~ lZoser. I am~ aprofessor of inedicineande director of the pulmonary division of University H'ospital, theUni- versity of California at San Diego in La Jolla. I am a consultant in pinlmonarv diseasoat the U.S.Navall Hospital in San Diego, as well as a consultant to the Clinical Center of the N ationall Institutes of Healtli in Bethesda, Md. I received my medical degree from, Johns Hopkins University Medical School in Baltimore in 1951. Between 1957 and 1'i968,, I was affiliated with Georgetown University School of Medicine here in Washington, D.C., where I becamechief of the pulmonary division of the hospitall and associate professor of medicine. During that same period,,I was chief of the pulmonary,section of t'heGeorgetown Clini- call Research Institute, which was sponsored by the Federal Aviation Agency,, and, a consultant in pulmonary disease at the U.S. Naval Hospital in Bethesda. I am a fellow of the American College of Physicians and the Ameri- ca.a College of Chest Phvsicians and a member of numerous profes- sional societies that deal~ with research in diseases ofthelunb , theheart: and blood vessels I am past president of the California Thoracic Society, and' a member of t11e board of directors of the California Lung Association as well as amemberof the Pulmonary Subspecialty Board of the American Board of Internall3Iedicine.. I have published moree than 120 papers and several books dealing with various aspects of pulmonary disease, and I am on the editorial boards of Chest and the American, Review of Respiratory Diseases. My ftiill curriculum vitae has already been presented to the committee. I am here today representing my own views and concerns which do not necessarily represent the views of any of t.he groups or insti- tutes with~ which I have been or am now affiliated. I was invit'ed to test.ifyy here today by you, Mr. Chairman. My medical career has been devoted! to~ researchy teaching, and pa- tient care relating to patients with lung disease. I am, therefore, ex- tremely concerned with det'erminimg, howand .vhylung diseases occur, and taking all steps necessary to prevent, improve, or cure such dis- orders. As a physician, my devotion to this cause has been strengthened by each patient I have seen whose life is, affected by lung disease. As a research scientist, my desireto learn the "hows, and whys" is intensi- fied by this interaction withpatient5. As acitieen, I have been vigor- ous inpromoting or endorsing public programswhiehmay reduce the incidence or severity of lung, disease; or improv e its treatment. In eac4 of these roles; I follow t'he same fundamental rulle of be- havior;,nanlely,that myactiens be based on, thebest medical- scientific information available. Whether I am at the bedsid'e of a patientor in a research laboratory, or in a forum, such as thi's, that ruledoesnot e change. Actions, must be, based'on facts, not emotions. However, the gathering of facts in science is ani ongoing affair. Therefore, at any given point in time, one must ask what is known and what is not
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36 known. Current truth is a composite of the answers to those questions; subject to modification as new information is generated. Every respon- sible physician and scientist recognizes this process. Yet, while seeking the facts; one would be remiss in neglecting, the intense emotionalism~ which surrounds health issues. Emotional factors themselves affect the health of each of us Patients with lung, disease are no exception. Indeed, emotions can have a powerful effect onhealth~ We all must becarefiil' to avoid injectinglarge doses of fear, guilt, and anger into people when we are discussing,health issues. Fear is a~ par- ticularly potent and dangerous kind of medicine. To use it as a direct or ind'irectt instrument of medical or public action ca.nnot., I feel, be condoned. There are already so many healthi fears instilled into our minds, we scarcely need newones. Indeed, my observations indicate that the mental and physical health of our cit-izenswoulds be advanced by the removal of fears not based on, sufficient fact. Otherwise, tahe~ average citizen is led to believe, so to speak, thatl, "Every day in every way I am doing something or being egposed' to something that is killing me." Mental and' physical health obviously are not fostered by such a belief. With regardl to: the question about publiicsmoking, and its possible effects on the lungs, the search, for a sound factual basis is espeeiallyimportant. I feel it, is absolutelyessent,ial that legislatived'eclslons relating to health, just like theonest.hat.I makeattliebedsides of pa- tients, be based on the best medical -scientific information available, and not on personal feelings or emotions. So, let me indicate to you the current status of our knowledge in this fieU In so doing, I think it is essential to beain by defining those issues clearltv. Those with strong biases tend to bltzr these issues. They have read. the last chapter ofthe myst'erynovel' and! . theyknowwho did it. I have not,,and I must accept, the story as it unfolds. Myr purpose here t'oday is to review what is known about the poten- t.ial health effects of atmosi?heric tobacco smoke upon.the lungs of non, smokers. Thatt is, the quest.ioni of so-called public, passive, involuntary, or second-hand smoking. In addressing this question, let me further define the issues which exist with respect t,olung disease, as foldows : First, one question is whether such exposures to cigarette smoke causee lhtng disease. Specifically, can such exposurescause asthma, bronchitis, pnenmonsa,,emphy.sema, cancer, or lung fibrosis? A second quest-ion,quitedistinet., is whetherindivi'dualswhoalready have lung disease are made worse by exposure to public smoking. The answers to t.hese two questions may well be different.. There aree many instances in medicine in whieh certain factors that do not affect healthy individhialscan affect persens with disease. Sblit isnecessary,therefore; to consider these issues separately. Let me address the quest.ion~of the liealthy indieidua]Ifirst; that is, is there any evid'ence-even preliminary-to suggest that exposure tosmokingin~ publfiac placesc.an cause acute, or chroni'c lung disease? I can report to you that there is no such~ evidence available. In at,tempt- ingtoanswer t;hisquestion, scientists havepursued tworoute.s. First,, measurements of the air sampled in public pl~aeesorin chambers in which cigarette smoking takes place. Second, st'udiesofselecteds groups of smokersand nonsmokers after special types of exposure to cigarette smoke. Iil tl tlliat in of mar I Iowev ,tance.smajor4 :L nt; -4elves. -tn nc;es: ~nb5ta.n ;rvroleil Even ()f ciga -~mok-er; 'Pliere t niaolv vof high, oranj'.( nftel are stu( j)arents;illd br( iilowe1-( . t h ab is; fift.ll,ye,Fnrtl nlents C irsg npC: -qune st. .-vmptcx. in «-hicll Now :Idverse IIere I of'p1Ib1 ],hVsem It; is ianusual (Irv air:, tlii) resi trQhes; iil Such nlar, ni Dr>sed tcIlowevc .rnd his (lirl'not In caii hltln`' w Such allieeallee bc>l ieftlbolief is
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37 De ple ,lsy bns pa- ~his ues iave lt.. I i ton- ary; is,is re t'o ~e?I ~ mpt- 1 First, ~ ;rs in °oups " Lrette ' In the first category: of study, numerous investigators have shown t hat, iii~ test chambers, cigarette ~ smoking certainly ea.n raise~ thec levels of many known components of cigarette smoke in the sampled air. IIo«ever, observations madeunder these highTyspecialiPed circum- 41;inices do not necessarily relatetothe public smoking issuewit'hout iuajor and unwarranted extrapolations. A numberof other studies have been done in public places them- ~«lves. Thesestudies have showni that, except under extreme circum- -tnnces, such as peak hours in poorly ventilated night clubs or bars,, ,nbstankiall accumulations of tobacco smoke, such as carbon monoxide,;tRrolein, et cetera, do not occur in public places. Even more important, however, is whether the demonstrated! levels of cigarette smoke in public places can cause lung diseaseini non- ~1r1okers: I am aware~ of no published data which support this thesis. 'I'lsere are parallels here with, theair poldut-ion, story in, which, after iu:niv Years of study, there is no proof that living, in an environment of hi,(;lr ambient,airpolltiition causes emphysema, bronchitis, cancer, oranv otherlung disease. Often quoted in connection with the question of disease causation are studies in whsch, retrospective questionnaires were use& to survey IP:ii'ents. Such studies reported an increased incidenc-e of pneumoniaiaid bronchitiis in, infants imder1year of a.ge. whose- parents smoked. lIowever, this increased incidence did not'persistt beyond the first year, tliat is. no differeuces were found in children in the second through fhft.li years. Fttrthei~nore, morerecEnt studies which inaluded directmeasure- inents of lung function, have not shown an io;npact'of parentalismok- ing upon either the sympt'omsor the lung function of children. These same studies did not show any impact of a spouse's smoking upon thesvmptoms or lung function of the nonsmoking spouse. This is an area in«liichmoreresearchisneeded. \ ow let, me consider the second' issue; namely, does public smoking ,ult-erselv affect the lun( ys of patientss whoaltreadyhave lung disease ? liere.I ha.vefound little scientific information regardingtheimpactg of publicc smoking on the patient wi'thasthma, chronic bronchitis,, em- l)lii•sema, Iting fibrosis, or othe-r lunb diseases. Ith is known, of course, that.the.bronc.hial tubes of asthmatics a.reuntisual2ysensit.ive t.oawide, variety of irritants, including cold air, (lrv air, and sulfur dioxide. It isalt;oknoR-n that asthmatics increase tlm resista.nce, in their airways, thatis, they narrow their bronchial: tlubes, if they directly imhale cigarettesmoke: S SiiehliYpersensitivlty -,.•,ouldl suggest that the asthmatic, in partic- iilnr, might have, increased symptoms-although transient.ly-if ex- i>o,ed to sufficient concQntrations of certain elements of tobacco smoke. Ho.vever, the onlyobjective study I couldlfind in this area. by Pimm~ and his associates, indicated that indirect exposuret'~o cigarette smoke(lW not a~lterthe hing functions of asthmatics. In cnring for lots of patients with lunr disease. I have encountered iibany who report increased sYmptoms in a smoke-filled environment. ~tach anecdotes, unfortnnatcly, are not useful in settling this issue because many other fact'~orscan provoke symptoms-including the belief that! ci,-'arettc smol:emave cause probllems, pa~rtlicularlyNN-hen thatbelief is stimlilatedbv thesmell of t~obaccosmoke.
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38 Therefore;base~d on theavailableevidence; I must concludethat there is no proof that smoking in publicc places adversely affectss pati'ent's with lung disease eitheracutely orc.hronirally. More research is needed in that area. In summary, then, I have tried to outline for you the issues to be considered regarding the potential' relationship between public smok- in;and lung,disease. The facts,that weno~v have do not establish that. smoking in public places either causes lung disease or worsens the status of patients with e.xisting lung disease: There are, of course,,a variety of reasons other than health effeet,- which mav lead to legisla.tion, that controls the publicc behavior of our citizens. But,in this society, we are all entitled to a, clear and honest statement about why our behavior is being restricted. Only then can we make ratfional judgments~abotit whether the financial and! personal price of such restrictions is just'ified-and whether it is better to:allo«• the private sector to deal with such matters. Whenever possible, hard facts should support public policy actions. In my opinion, there is not now a sufficient body of hard fact~s to support the view that. public. smoking poses a health hazard to the lungss of the nonsmoker. If there -were, I' would be among the first to press for ai legislativeremedy. I believe strongly that what weneede now is more research about the basic issues I have reviewed, not legislation based on the fal§c premise t'hat the answers,alreadv are available. To do so R-ould,in fact, indi- rectly st'ifle legitimat'einquiry into t.he.se-iQnport'ant health issues. Thank you. f The curricuiumi vitae of Dr. Moser may be found on p. 25$.] Mr. JotiFS of North Carolina. Thank you, Doctor. Do anyy members of tlie subcommittee have any questions? Mr. Sebelius. Mr. SFBr;,LiUs. I appreciate your comments, Dr. .lZoser, as a non- smoker and as a Congressman who has a distriet' that growsno tobacco. I have one question thatgoes beyond the scope of this heari'ng. Youaddressed this and Iwantt'o compliment you on yourrerslarks re('ard- ing the. effect of smoking on the nonsmoker. But if I can get. a free shott in here, I sat andi R-at'ched, a father-in-law, die of lungcancer R-howaso a very heavy smoker. I saw a very dearlaR-partner die of lung cancer and lsewas a very heai-yy smoker. Do you, in you: vast- experience in the fieldd of pulmonary diseasein medicine, personally feel that as far as theindividuad' is concerned and his own consumption of cigarettes, it could be acauseof lung cancer or an irritant, or n•hat have you? Dr. Mosra: I think vshatwe aretalkingabout here is statistics. Mr. SFBEr,rrs.I am talking, about theindividtlal himself who is a snioker. Dr. _llosEi?. I think wearet'alkingabout a statisticat anali-.siswhich has indicated that for some reasonunknoR-n, there is astatistical'rela- tionship between certain types of lung cancer and certain levels of' cigarette, consumption. That is a statistic anditl is notrea11y a scien-tific fact. Mr. SnBELics. Theincid'ence seems to appear often enouzh. I cite the two that, are very close and very personal to me. As far as t'he individuali is concerned,, it is somethiruc, that', he is taking upon himself.I d'on't desire to legislate anythiiig. I don't smoke and don't want to.. I have my sons and they don't smoke. 9 t B+ that t oda; upor I a.p TI 111 subc( _lII vatio the Y . '`in t abow with «-het!: Ii whiel Educ idm comn smok thele: estab_ I am taken a pol or fac Dr. It other:tolma ative, Dir. mony edge,, that . first t i rritial aroni< To when tee, a,Lppre Dr. _l:f r. Dr 01117 h could otller D r: recall peoplc
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e that iffects , earch I to be smok- h that xs the I yffect,, 5f our ~onest in can, tsona,l' allon- ~' hard ~ non- acco. G, You ?gard- !e shot Ib was ~ancer in the far as '7 Aes, it tics. 1oisal which~ I relal•els of scien- I citle as t'lie, msel'f. !int to. But, I am interested in seeing to it'thatwhen we react to something, that we react to it in a scientific manner as you have explained to us today. I am veryy averse to having the Federal Government impinge upon everybody's rights on the basis of supposition. Thrat is the reason I appreciate your test'imonyon, thespecificsubjeet we had today. Thank you, Dr. Moser and llr. Chairman. Mr. Joti Es of North Carolina. Are there any other members of t'hee subcommittee with questions?'b1r:Wampler. Mr. WAMPLER. Thank you, Mr. ChairmanL I hav.eone brief obser- vation. On page 9 of your statement, I think you really surnmed up the whole question before us when you spoke these words. You said,, "in thsssociety, we are all entitled to a clear and honest statement about why our behavior is being restricted." Now, I couldn't agreee withi you more. I thinkthat is precisely what the situation ought tobe , nhether we are talking about smoking or any other habit whichi wemight liave,,as long as it is]egall I refer again to Dr. Fisher's testimony earlier this morning in wliicrhhe was talkingabout the study of the Department of Health, Education, and Welfare in colls,borat.ion with the Federal, Aviation .~:dmini'stration when they undertook the study of smoking aboard commercia.l aircraft. As Dr. Fisher said, that study concluded that smoking did not present a healthi hazard to t~henonsmokers. Never- theless, in spite of that conclusion, the Civil Aeronautics Board did establish smoking, and nonsmoking sections aboard! aircraft. So, what I am saying is that decisions of t'hat type and other decisions being taken byregulatoay authority and legislative bodies, then, is really a political or an emotional decision and not based on scientific data or fact. Would you agree with that?Dr. Mosr,R. That is absolutely correct. I think as you haveheard' from me, and as you will hearfromr others, the data are not there. I am not one to say that if you, want to make an emotional judgment on an, issue that it is not one's prerog- at.ive, but at least you ought to tell' people that is what you are d'oing. blr. WarsYr,Ex: This is why I particularly appreciate your testi- mony and that of others tod'ay.. This is the first time, to my knowT- edge, that this subcommittee has heardtestimony of this type: I think that at least there ought to be abalanced' record. I would be theffirst to concede that to some people the smell of tobacco smoke is i~rritatingand obnoxious just as the smell of colobmeor other st'rongaromas miglit beobnoxiousto other individuals. To predicate these types of actions supposedly on scientific data wlien it is not. supportable, I think,,is, a, matter that't'his subcommit- tee, and indeed the Congress, should be deeply concerned about. I appreciate your testimony, thank you. Dr. bios~:a. Thanl: you. Mr. JoNFS ofl NorthCarolina,. Thank you, Mr. Al'ampler.lhi1loser, I belie.veyoui indicated that emotional fact'ors can affect our health. Doest'hat mean that ai penson's fear of t'obaccosmoke could actuallycause him or her tohave trouble in breathing orsomeother respiratory problems? Dr. '-Niosrx. Wehaveald been, ^fr:~r' Mr. Chairman, at times; and I recall the first time I made api ..blic -ment before several hundred people. I was pretty short of breath. `~ -1 a very rapU heart rate: I
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40 was perspiring, et cetera. So, there is absolutely no question of the tremendous impact of fear and anxiety on body functions. If you translate that into a cue, for instance, the smelling of cigarette smoke means I am about to die, that translation is unfortunately being madee by a number of people, and! I think that is a cue to have all of thee symptoms that I j iust described. Mr. JONES of North Carolina. I woulldl assume, then, that is about the same emotional reactioni that most of us have every 2 years. [Laughter.] Dr. MOSER. Yes. I would think so-about every two,, I think, sir. [Laughter.] Mr. JONES of North Carolina. Any other questions?'Mr. Jenrette. Mr. JFxxn<rrE. I would like to go one step further with the emotions, if I might. I wonder, would the same emotional effect, in your opinion, be prevalent for one that was e$cessiwely chewing gum all the time as a part of one's endeavor to calm one's self ? Is that ani analogy that eould be,made ? Dr. MOSER. I think perhaps a better analogy would be the person sitting next to the person chewing who feels that somehow that is going to impact on t'heirhealth. We are talking about the public smoking issue, that is, your perception that somethingthat'somebody eli;e is doing is going to hurt you~ That is, I think, what the gut issue ishere: If you are convinced that inhalation of alcohol flumes from the personnest to you, or the loud popping noises that sometimes come from chewing, or any of those things, are going to hurt you, you~ get a serious emotionall response: The more you areconvi'nced of that rela- tionship, the stronger your emotionali reponse and the stronger all these physiological responses I mentioned. Mr. JEtinE=. The same would be true of nail-bit'ing,, I assume. I have seen people that were just horrend'ously frightened about sitting by a person who was biting their nails all the time. Dr. bZosnx: And! the cues in society today to be afraid are mult.iply- ina -every dayy in the newspaper and television we see another reason why we are terrified to drink water, walk down the street, eat any- thing-and I think as long as those cues are mounting-one of them may be t'lie smell of cigarette smoke-we are creating al societv in which everybodv is continually seeing some cue that terrifies, them or annoy s them enough to have some reaction to it. Mr. JF:cREarrr:: I couldn't help bnt draw attention to television ad- vertlisements while you were testifving about the reaction, that certain animals have. When the bell would ring, the animal would know t~hat it was time to go get drinks of water or to hav.e some food. Maybe that was thee same analbgy. For those of us who are under emotional stress alll the time, as those of us in politics,, t}aebest and safest thing to do is to continmie wife-beating because that, at least, is in private. I Laughter.]!, Thank you,l4Tr. Chairman. Mr. JotiFs of North Carolina. Does anvbody else have a question?, If not, thank you verv much,Dr: _lfoser,foreoming this morning.Dr. IGZiosF~. Tharokyoil_ Mr. Jo.~-ES ofNorthCarolina, Our next witness i's Professor TheodorD. Sterlin(y of theSimon, FraserLT'niversityof Burnaby, British Columbia. t g STA7 i IA Bt Di Il I plin,I7 agen t ion, meni C.`an, and _lI and fiicm IB-.N . tami thel _li T: my data t'.liee heal lherk men T tion nu1r, ther ings and eli~ F srno polll Prc: S inlp n1eadhvc. T Snio I c,xtE .:T; the
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f the you moke made Ff the Rbout fte. tions, inion, time P that erson iat isi ublic ~bocly ssue from come get a rela- er all me. I tting tiply- 'eason any- them !tv in them n ad- ~rtain v that davbe tional thing atie. STATEMENT OF THEODOR D. STERLING, PROFESSOR, FACULTY OF INTERDISCIPLINARY STUDIES AT SIMON FRASER UNIVERSITY, BURNABY, BRITISH COLUMBIA Dr. SrrMr,rNc: Mr. Chairman, and gentlemen, I thank you for in, vitingmeto appearbeforeyoursubcomrnittee. I havea brief statement that I will read. I am Theodor D. Sterling, professor in the faculty of interd~isci- 1)linary. studies at SimonFraser University inBritishColumbial. I have served as a consultant on statistical problems and data man- agement to the National ScienceFoundation,Vetierans' Administra- t ion, Public Health Service, Department of Agriculture, Environ- nQental Protection Agency, Federal Trade Commission, Environment('anadn, anumber of citizen groups dealfingwith environmentallissues, and various industries. JIyresearchi has been supported by thehational CancerInstitute and other NIH institutes,, tlheVocational Rehabilitation Administra- t ion, the Council for Tobacco ResearchrT.T.S'.A., Cincinnati Milling, I I3.l1, and others. I have served as an expert on environmental con- taminants to a Royal Cbmrnission in Canada and! to committees of tlieIT.S'. Sena-teand State legislatures. My curriculum vitae has been submitted to the subcomrnittee Thefield in which I teach and in which I condluct't1iemajority of my research concerns the collection. processing, and interpretab'ion of data. Several of myresearch efforts haveconcent'rated spec.ifical'lyon thoanah-sis and interpret'ation ofdata concerning environmental lfealtli problems such as the effects oflead, radiation~, air pollution; and lierbicideelposures. DTy recent examination ofthe internal environ- ment of public buildingsis a~ reflection of these interests. Thef<ict. that the air in public buildings often contains concentra- tinissof fumes, dustls, and the like appears to have been ignored by a; immrberofscientists, environmentalists,, and architectis Nevertheless, there isa high exposure tomicroehemica~ls in the air ofmanybuild- iwI.-s. and any solutron that will help to improve the situation is needed~ andwelcome. I arn„ however, opposed to an approach that would restrict or elitninate smokingof tobaccoin, buildingsflor the following reasons: First, contrary to popular belief, scientific evidence shows that the srlroking of tobaceois a minor and often insignificant contributor to l)olliition. Elimination ofthat one source would not decreasepollutants IPresent toany meaningflulleatent. Second, a rulerestrieting or eliminating smoking would give t'he>>lrpression that effective measures had!been taken when in fact nosnch measureswould have been taken. Such a rulewould serve only to(lk-ert attention away from the real sources of the problem. Third, prol-iding acceptable indoor air lies not in interfering with S»>eker; butior effective v.vntilation practices. Ii tivill srunmarizethe evidence that supports these,staternents. A more oxtensiveanalIvsis is contained inimy, article, coaaithored by Kobavashi, x1>osure toPhlhltants in F)hcl6-ed Living Spaces," publishecU in theFebruarv 19-t7issueof Environmental Research, 1-35.
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42 To summarize, a good deal is known about pollution in public buildinb : Today's large office and other buildings are for the most part semi- sealed environments. In fact, they are very much like submarines with many similar problems. The amount of fresh air allowed to enter is carefullly regulated and recirculation of largeamount'sof used air is commoni practice. Spe- cial filters as well'! as chernical cleaning and! perfuming techniques are used to keep inside air clean. This clean air, or what is called clean air, may not smell foul, yet may contaiir large amounts of eontams nants. Incidenta.lly, this is also true for the many homes that rely completely on a mechanical indoor temperature control syst,em. Jfany such private houses and apartments arecarefully insulated to preserve fuel but lack adequat,e ventilation so that high levels of pollutants are sometimes generated :rnd! entrapped in~ such dwellings. But the laxgest burden of toxic air pollution~ contaminants is regularly borne by people who work in orfreqttent large modern structures, ~ The, article in Environmental Research I ment'iioned previously con- tains an exhaustive review of levels of pollhitantssuchi asdust, sulfur dioxide, carbon monoxide, carbon dioxide, and' hydrocarbonsfounds commonly in t'~heair of di6rent tlypes of buildings. Thesesubstanees,are ind'exesofl the contentsoftlheair. A good por- tion of these particulates penetrates a building from the outside and' becomes entrapped in it. Therearealsomanypollution sources indoors. Carbon monoxide, for example, is produced! i'nbuildingrs~bycooking, oxidat'ion of oils and lubricants, aging of paints-especially on steam- pipes, and any heatingequiprnent that oxidizes fuels. «hilethe amounts of carbon monoxide produced by aging paints, for example, are small per unit area, many=publicbnildingshave immensely large areasof painted walls and pipes, so that the contribution of carbon monosidetotlhe atmosphere from~ this sourceisfar from trivial. Extremely higheoneentrations of' hydrocarbons, come from cooking, paints, varnishes, lacquers, paint thinners, solvents, cleaning fluids, vinyl, linoleum, asphalt tiles, rubber and plastic cement, and bonding compounds. Oxides of nitrogen areformed by elecNric, arcingof armatures, short, circuits, and operation of any type of eiectricall equiipment. These same sourcesalso produceozone. H4~h levels ofnitlrogen diolideassociated with gas cooking have recentlyy been reported. I would refcryou to "Differences in -N©z Levels in Kitchens with G'as or ElectrilcCbok-e.rs," from Atmospheric Environment'1'2: 1i379-1381, 1978, by R. J. yV. lfelia and others. Sulfur dioxideand~ hyd'rooen sulfides from outside air aretrapped within abu2ldingand may alsobe produced bybact'erial actioninsidethe building. Ammonia~ is produced as a biological end' product in sanitary tanks and toilets. l:iercury vapors come, fromimeters and ga.ges.. Triaryl pliosphatleconnes from hydraulicflaiids: Formaldehydesand methyl alcohol fumes are end produc.tsof osi- dation, of the methyl alcohol used! in many t.vpes of office equipment. Asbesto& and other fibersar.-_ relleased into the air cir.culating, thrc latii SA heat duat F acti ;-1ar and oils, Sulf; and T: well carli: ing 1ng. pan< vou Gas adk,< autlliFc 'huce tihat peril Vidu level expc C, . «• it'hinsic: Oncc uut , In takei reltit cone agec cone in th Smo T [an, "Cor W.( •,92. In i'ndo( Fi aiir ii funic Se
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iublic i semi'- I with~ d and i Spe- es are clean ;tami- t rely Ntanv, ,serve its are a,rgest pe by I y con- sulfur found 3 por- Le and doors: teking, am- e the mple, ilarge arbon i. aking,. fluids, jnding short b same ci at!ed 7011 to Cook- J. VV. apped! inside 43 through between-floor airspaces that have been sprayed with insu- lating materials. Serious and little recognized sources of' allergens and fungii are heatino, and cooli'ng unit!s. Organic~substances grow inside ventilation diu:ts and are cireulated throughout a building. Finally, substanees, are introduced insidebuilelings by many human acbions~ Byproducts of inetabolicactivity include carbon dioxide, ;.;landularsecretions, organic dustpart.icles from hair and skin„mucus, and dead cells. From breath alonecome acetic acid, acetone, volatile cnils, methane, and hydrogen sulfide. Fromuriue-come.s ammonia and ,ulfates. From sweat and! glandular secretionscorneurea and lactic and ortanic acids; The danger of carboni monoxide poisoning from faulty heaters iss wellhnown. A ot sowell known are some of t'heother sourcesthataffect carbon monoxide.levels. In a new and not-yet-published study involv- ingprivate dwellings, R-efound that if gas, stoves are used' for cook- ing, very highleti-els of carbon monoxide are generated when potsor pans are placed over otherwise clean burning,- flames: i n ould refer you here to"'Carbon lionoside LevelsimResidential hitchensUsingGas Stoves" by T. Sterlingand E. Sterling. I would ah;o mention that. adrancecopies of the manuscript. may be obtained from the seniorauthor. , Forty to 120 parts per million of carbon monoxide may be pro- (luced iia tlie tiimeit takes to cook a meal. I should point out here, that 50 parts permi10_ion istheindustrial matiinum concentrationi I>erinitted in industry, but not,at home, I am afraid to say. All indiL viduals in the vicinity could be. rout-inelyesposed t'o carbon monoxide 1k,vels that equal or even exceed the standard for maximal industriall exposure. Carbon monoxide is one of the substances that is not only produced \vi'thin buildings but also introduced fromtheoutside; and its levol insideis directly related to the structure's proximity to the street. Ohce insi'de„eltlernallygenerat'ed carbon monosi& . issPread through- uut a buildii<ig, by the ventlilation system. In my review of data on pollution insid'epublfi¢ buildings,, I have taken special notice of studiesthathave measured levels of tobacco- related substances. Based upon my review of' these studies, I have concluded that carbon monosidevalues in public rooms under aver- age conditions of ventillation~are~increased veryy litt.leby smoking. This conclusion isconfirrned by reports that the amount of nicotine found in the air of publi'c phices iseztremelv small. I referhereto'`Tobacco~ Smoke in PliblicTransportation, D'avellinTsandl«'orkRoonis"by H. l1Iarulseiu and E. E'fTenberger, Arch. Hyg, 141: 383-400, 1957, and "Concentrationsof tiicotineand Tobacco SniolteinPubllic Places" by W•C. Hlilids and lI. W. First, New England Journal of lledicine, 292: 81I-8'115, 1975. In conchision, several iunportant facts emergefrom the study of i1odaorpollutants. First, alarge number of studies have now demonstrated that. indoor airin: most public and'many privatlestructures is polluted with toiicf tir»es, dusts, and allergens. Second, some of these pollutants may=reach very high levels.
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44 Third, smoking is a minor and often insignificant contribut©rtopoldutiom in buildings. If there is proper ventilation,, then under normal conditions, indborairwill not differfrom~ outdoor air or may be even less poll'tited, whether or not there is smoking in the building. If there is not proper ventilation, then indoor air will be more polltiited than outdoor air,, whether or not there is smoking in the building. Any approach to the problem of insuring a reasonably elean~ indoor environment that is aimed at removing a specific source suchi as tobacco smoke rather than removing pollutants in general v-ould' do little more than givethe impression that effeetiveactiions had' been taken when, in a,ctuality,littleor nothing would have been accom- plished. I must join with the first witness, Dr. Fisher, in putting th2s issue, aswell as tliehealth issue, into:some reasonableperspective. Tha-nkvou. [IThe curricuhzm vitae of Dr. Sterling may be found on p. 282.] 11Tr. Jo_NES of tiorth, Carolina. Thank youy Dr. Sterling. Are there any members of the subcommittee who might have a duestion?Mr. Whitley. Mr. WiiizLEV. Thank y,ou, 11Ir.Chairman. Dr. Sterling, you concentrated oni carbonmonozide from tobacco smoke ini your statement. Hlowever; I assumethat adequate venti- lation would alsotake care, of the other substances produced by tobacco smoke. Is that correct? Dr. STERLING. It ivouldl takeca-re ofa11 stbstancesproducedn-ithin tliebuilding-by the activities i'nthebuild'ang, by thema¢hinery in the building, or by the activityy of man in that bu1lding, includingsmoking. Mr. WirrrLr,Y. From whatever source? Dr. STExr.r.Nx. Ft•om, whatever source. bir: WHiTiLFy. Thanky.ou.I have one further quest.ion,Dr. Sterling, if I may.. It seems that either we are increasing the level of pollution in the air, or perhaps we are just discovering what has, been therealll the time, but it is a fact that while all this has been going on, thelifespan of the Americani people has been increasing. A~'Tould you not! say that. .ve~ have demonstrated a, ratherremarkable abillity to adapt b'o ourenvironment, whatever it is? Dr. STrRi.rXc. I would say so, yes: MnWHITLFY. As one of the earlier.vitnesse,s testified, every day and eveiywayy things are getting worse and worse, and everN-thiuigNti e do is, killing us. Yet, at the same time as we arebeingtr~ldl that, thelifespan of theAmeriean people has increased dramatically. Is that not correc:t'?Dr. STFRraNc. It isvery likely because the actions ofindtastrS whsch, very often. may produce something harmful, are countered by the public health community which, balances that. I think the modern buildina is~ a good example of what you say. Themodern~ building was first constructed to pron-ideman. with aclea.ner environment. Older buildings used to justt burn a fire in the middleoft:hefloor; and everybodyy sat aroundl choking. 1 effo n1@: bu2 cre. bui. pro _l. :! C not gas. ,t re bur; mat in t thati eXp( I acce D .\ 1 reas stie] ))am DD i t! ree safe toul siml vent ryas. _l1 mav D sour to 11 Sour D I wc hein «-o,u \o< Van S( _lI intel We \, T1 3x-
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45 ~utor to I p, indoor Jolluted, )e more ~ in the PI r indoor ~uch as ould do ~d been I I accom ~ ssue,. }s i ~H ~have a i !!t'obacco. e venti- iiced by ~ within nerv~ini ,'chiaing ~ in the all the ifespani 5av that '0 ;toour day and -%Z'e.(lo7s Lifespan ^orrect? r which, bv.the vou say. with a e in the Unfortunately, as the building becomes larger and larger, and more e1£lort is being,made to make this a high-quadity environment, more and iuore machinery is intiroduced, more and more fuel is being burned, the building is close& off to the outside,, and more internal problems are created! / Adequate ventilation and adequate d'esign for ventilation of a public building would controI that so that we may enjoy whatever air -God! provides for us in this country. Mr. WHSTLEY. Thank you very much, Dr. Sterling. JONES of North Carolina,. Is there anyone else ? Dir. Wampler. AIv. ti`':»rrLEU: Thank you, Mr. Chairman. Qh page 5 ofl your statement, Dr. Sterling, you say, "In a new and! not-yet-publi'shed study involving private dwellings, we found that ifryas stoves are used for cooking, very high levels of carbon monoxide :rregenerated wheni pot'sor pans are placedl over otherwise clean- lmrniQlg flames, and 4'0to, 120, parts per million of carbon monoxide may be produced in the time itt takes to cook a meal, and alll individualls in the<vicinit'y coul& be routinely exposed t'o carbon, monoxidelevelk that equal or even exceed the standards for maximal industrial exposure." I believe you also said that 50 parts per million i's normally the :<cceptedl industriall safety lovel. Is that correct? Dr. STI~',RILING. That is correct. Mr. W.v_NnPr.Fx: Well, onecould read this statement, and I have noix, a4on to doubt it at all, as sayingt'here probably could be more ,oientificbasis, for banning tlheuse of gas to: prepare your mealst'han hmnning tlieuse of smoking in public places. Would you say so? Dr. Srr:ar.iNc. The problems again, is adequate ventilation. Perhaps it reflects on the illusion we have had for many years that the home is al safe place and that cooking in the kitchen isasafe activity for a; woman to nndertake: It may not be and~ could be made again a safe activityy by si mply eliminating the carbon monoxide from the ki t.ehen byadequate Ventilation or, to do as you suggest, not to use gas-to forbid natural ,as. This might relieve Vour President's problems at this time. Mr. «'A.crLEx. WelI1,~I did not exactlyhave, that in mind, but, you mav be right on that. [Laughter.]I Dr. Sterling„in a serious vein, ifi' you arecorrect'that'therearemany~ources of indoor pollutants, can you explain .vhytheattention seems to ha~~ebeen focused on tobacco smoking and not some of the other sour.ces that you have described ? Dr. STERC,rNc. Tobacco smoking is visible. I am not an allergist, but' Ii would imagineapcrson with an allergy walking into a building,and bc'vir exposed to~various allergens growing in t'heheating and vent:ilat- ductlsand feeling poorly as a response, then spotting a smoker, «.oulel saiv, ccAh, that is where it is from." It is just the visible effect. \o one can see the fungi and bac?teriai ini the building, but everyone c'1n see tlie, person smoking. So; tosome extent, it isexplainablethat.vay. Jir. Jcr:~F.sof ~ort'h Carolina. Gentlemen, I am goingt.ohave to intcrnuptat this point. We have a quorum call.-ote in the nextroom~ so Nve will takeabout a 5-in inuterecess. 'Thesnbcommiitteestands in recess. 3 4- [21 0 - 7 8- 4
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46 [Recess t!aken.]j Mr. JoNEs of North Carolina. The subcommittee: will resume its deliberations at t.histime. At this time, the Chair is happy to recognize: Congressman Hubbard of Kentuckv for brief remarks. llr. H~L sBArtn. Thank yxou,llr. Chairman. I appreciate this: opportunity to visit with t~hesubcommIlttee and apologiee,forha.-ing to leave a few minutes ago for avote: I would like tobrieflystat.ethat, as'you mighte5pect, being froin Kentucky,I do represent t'~housands of tlobaccogrowers and foresters, as manyofl those in the roorn know. The tobacco industry-is verv important totheeconomy of Kentucky.. As a Stat'eSenatoriniIientucky, Ivoted for tax funds from our Statetobeused in researchf'or the real answers to4his controversial issueaf.v.hat causes diseases~such as,asthma, bronchitis, pneumonia. emphy- sema, cancer, 1ungftbrosis, et cetera. Hopefullv, as q- resultt of these hearings, there be more Federal tax fnndsspent for similar types of research on this controversial issue. Thank you, D:Lr. Chairman.Mr. b1ATxzS [actingchairman]. T hank you Dlir. Hubbard. Thechairmaji'spresenceis rectuired'in, theother comrrnitteeroom for a vote. In the meantime, .ve will be„ in with the next witness. Thenelt «-ithess is Dr:John Salvaggio. Dr. Salvaggio; we would be glad to hear from y~ou at•t'his time. STATEMENT OF JOHN E. SALVAGGIO,, M.D.,, HENDERSON PROFESSOR OF MEDICINE, DEPARTMENT OF MEDICINE, TULANE UNIVER- SITY SCHOOL OF MEDICINE, NEW ORLEANS, LA. Dr. SAr,VAccro. Thank ~~ou; Mr. Chairman. I am John Salvaggio. I~am a physician. My current position is that of theHenderson Professor of :lledicia_ieat TulaneMedical Center in New Orleans. I am alsoAirector of! theAlliergicDiseaseCenter at tihat institution, which is oneof a d'ozen or so in the Nationi doing research on allergic diseases. I also direct!the training program in allergic and immunologic lung diseases at. Tulane. I received an 3Z.D. degree frornL.S'.U. Afedical School and did mv ; ost.-gra.dlratework in allergy, and immunology at,theHar%-ard' A2edical School and Massachusetts General Hospital in Boston. Like theot.herdiscussants, I amamember of n7anz- professiona.l and medical societies. I think the most gerrnaneto this~diseussion are theAmericanBoa-rd of Internall 11Zedicineanrl the American Board of Allergy and Immunology. At present, I am one of the governors of the American Board& of Internal Medicineand the cochairman of the American~ Boardl of A1lerawand, Irr4munolog y. These are the certi fyingaaencies that pass on the eomlretenceofphti,sicians who: practic,ein these specialtiesin the country. I am also head'of a taskforce~of the National Institutes of'Allergy and Inrfectious Disease on Occupational and Environmental Respira- torv IDiseases, and I am on theadvisorv comrnitteefortlleDivision of LungDiseases of the. Natiionall Heart, Ltmg, and Blood Institutes. Ihavewritt~en about 190papersand manuscripts in the literature in this area, and you have my curriculurnivitae. Lik. and n( I h,, not ki ihere produ "7.ussm ,rre al, incliit-i ,ictual. Bif, feel it Iliscus I~t! i s vt erms. Arr f'inne the ey, ~ ornfb concer Asr ;Iir po least, (t64s high cl The t.rnt'is, are pr nonetl, Oir ti It is a of ant ~"lobul An proteci For e--, kind o and th outthE So, ; t:'ctit-eAn esterl i (liffere rnent o in(lhicec,ertiair The some I is usua nehessf An • popula popul~-
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ing front foresters, ;entucky. Dur Statle sial issue , emphy- of thesee lar types n is that enter in r at that research allergic degree allergy chusetts iona.l and 7 are the 3oard of ;rnors of tn of the ~rtifti ing actice in Allergy i~espira- vision of itutes. iterature 47 Like I)r. Moser and others, I ami here to express my own opinionss and not those of any constituent society. I hawe been asked to try to tell youi what we know and what we do not, know about tiobac.cosmokeand allcrgies, since it isclaianed that there are millions of people who are allergic to tobacco smoke or its products-according to estimates in the literature by Dr. Bernard 7ussmani, thereare up to 8 or 9 million "'tobacco: allergic" people. There ;ur also anecdotal reports that the conditions or symptoms of allergic inditiridualis and~ individuals with various respiratory diseases area~•t uallv aggravated by tobaceosmoke in tlieatmosphere. Bef©negettingintoai5-minute discussion of t.hese areas; however, I feel it imperative that I define three terms that I am going to use in my discussion. These three terms are: allergeii,,irritant, and! immunogen. It. is very important that we underst'and'the differences between these t erms. 1n irritant, in t'hecontegt that we are going to use it'today, is any fiuneornos~ioussubstancewhic-h results in sy.mptomsliketearing of the eye, coughing, wheezing, or similar nonspecific respiratory dis- ~umfort' that generally affects all people if present in sufficiently high concentration. As examples of irritants ~ce might use automobile exhaust fumes, ,i~ir pollntion andi fumes from industry. Certainly, in myjudgment at least, tobacco smoketivotild fall in that area. All of these fumes and (lusts can have this irritant effect if they, are present in sufliciently lligh concentrations. The nonspecific irritant response usually disappears after an irri- t,cnt is remoATed and I think the .ti idely held view is that these irritants :u-e pri'marily.a bother and a nuisance, perhaps: severe to some but, nnnetheless, only a bother and a nuisance: On the other hand, an immunogen is quite different from an irritant. It is a generall term for a cliiss of substances that indueet.heformation of antibodies from various blood proteins that are called immuno- ~~lobulins. ~_~n irnmune response to an i~nmunogen can either be harmful or I)rotective. It is usually thought of in the context of being protective. ToreYample, a common vaccination program would depend on this kind of protective function. One would beimmunize4 .vi'thavirus; and this would protect oneagainst development ofa: disease through- out the rest of one's life by development of these antibodies. 8o, an i'mmunogen isoft.en thought of in theconteat of being pro- tectin.-e and is quit'ediffcrent froman irritant. An allerg en4 on the other hand, which is what we arerealdy inter- (~stecl in, is still different from animmunogen ancU an irritant. It, is a(lhtTerent kiiid of an immunog en that reallyaffeets only a certain, seg- inent of the population in ettremelysmall quantities. What, it, does is to in<lilce a, 'sensitizing"' kind of an antibody response mediated by a certainkind!of inzmunoglobulin, namely immunoglobtilin E: The antibody response to t'heallergen is often thoiight of as causing ,0me ki2rdof discomfortl or symptom like wheezing or sneezing. It is 1isuallv thoughtt of, in thatcontett, as being harmful although not necessarily so. .1nallergen generallyafllects only a certain s~nall segment of the I~opulation, as opposed! to anirritant which may affect theentire Population.
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48 The allergic subject is, byy virtue of a certain kin& of genetic makeup, prone to become sensitized to an allergen. For eaample; a few people are allergictlo strawberries. A few people are allergic torag)veed pollent biost people, howev er, a~renot allergic to these substances. Contrary to claims about tobacco smoke allergy,,in~my judgment,,it has, not been clearlyestablished that allergens for man are present in, tobacco: smoke. To date, most previous studies have actually failed too analyze tobacco smoke to see even if it has immunogenicor allergenic properties. Furthermore, there has been, a general' lackofadequateclinfical information on the individua-lswho claim to be bothered by atmospheric tobacco smoke. As the other speakers have said, we certainly need more research in this area. The claims about tobacco allergy aetually stem largely from studies carried out in the past using tobacco leaf, and I stress the word, "leaf," as opposed to tobaccosmoke. These studies report that extracts from tobaccol leaf can elicit allergic responses in bothi smokers and non, smokers, but the presence of allergens in tobacco lleaf does not neces- sarily mean that allergens are present imi tobacco smoke. They may be, but one cannot conclude thelat'~tler from t!heformer. Why? Becauseof the very real possibilitvy or probability that these allergens do not survive the burning of tabacco. Most allergens, if heated or treated in certain ways, lose their potency, and are no longer allergenic.Indeed', studies by very reputable investigators at the DZay.o Clinic,Di•. Gerald Gleich and his group, have strongly suggested that there are no aldergcnsfor man in cigarette smoke. These investigators demonstrated a lack of an antibody response in man~ to smoke extract, using a very sensitive test, that is used to diagnose common allergies. In addition to the studiesof t,he.Mav.o Clinic group, there have beeny as you mizht anticipate, a lot of clinical'studies on persons.cithivarious, allergies like hayfever and asthma. These studies have tried t~o estab- lish somekibdi of correlation between tobacco productson~ t'.heone hand! and allergy orillhlesson theotlherhandL I spent a lbt of' time rev ieR-ing these studies., and' I think it is fairly safe to conclude that most'of tliem, suggest that t'~hepredominant effect,'of cigarette smoke is one of an irrit~ant and! not an allergen. In addition to these studies,oni allergicindividuals; there have been a few-and I stress, very few-studies onthe effects of ordinaryy atmos- pheric~ smoking on healthy, normal, nonallergic people. I willi justt mention one of these st~udi'es by a~ Dr. Speer. Dr. Speer studied 191 allergic and 250 nonallergic persons byy quesr tionnaire and byskini testing, with tobacco leaf extract. Although he reportedl positiveslcin, test reactions in 28! of these allprgicindivid- uals and, indeed, some of them-up t'r,one-fourth of them--developed some c.ough, or nasal symptoms, there was no correl'a.tion between the allergic kind of skin reactivity, on the one hand, and'the severity of the claimed tobacco smokesympt4ms. So, Dr. Speer correctly conclude.d from this studyv that't~he symptoms~rereprobably notallergicresponses but, rather, imrit'ativ.eresponses. Recently, Dr. Becker and his coworkers ihr NenrYork reported in very reputable medical journals that extraction of acertaior compound from the tobacco leaf as well as from tobacco smoke and tobacco! smokecondensat'e, produced! positiveallergy-ty.pe skin test rea,ctionsin 21, out of 31 subjects. They al'soreported an antibody response of tlie I IlFinr n1an; t her.e "4o th more Il the v «'c l;rbor i {k)es v;un s hittt r wlrile, Irenic nram ]te: ity of. LcforIn s~~iol:a immL I,onrr 1'1'1 JlrTh( C'artehndge So, [ RE 1Ir: der; p «'eThE the In We STAT' SOB' INI INI
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i akeup, people. rgweed Zent, it Sent in Ped to ~rgenic. [equate ,red' by td'y we sttidies`cle af;"' ;s from d non- Ineces- hay be, ~ecause !do not pit'ed in Clinic, ~t there ~igators ~Ytract, lergies. re been, p.arious estab- he one ~ fairly teffect' ,y ques- iugh he ndivid- veloped een the y of the ichzded sponsess rted in :ipound tobacco tactions, onse of the IgE variety that I talked about before in the newborn rabbit, iising this, . so-called purified compound. However, their studies inwan, at least, included only a small number of subjects, and more, t!iere «-as grossllyinadequate clinical inforrnation, available oir them. -~o the significance of even these studies is unknown, and! considerably more research isneeded in thisarea. I understand that there are other unpublishe& da-ta questioning1~hi, verypurityof Dr.Becker's compound, as well. We at Tulane are alsoleurrently doing quite a few studies in ourl;1boratorti,on tobacco leaf and! tobacco smoke. Actually; our research , ioesindiaat,ethat both the leaf and smoke contain components that c:ul stimulate an immune response in certain experime.ntaI animals, h1iV not necessarilvan allergic response. I'want to emphasize that, while our data demonstratethat smoke components are immuno- ,renic, they do not establish the allergenicity of these components in noan. Rc,earchis now underway in our labstot.est t-he possible aldergenic- it %- of these components in man. Certainlly; more hard data are needed h~fore.ve can make any definitive statements in this regard. Iin conclusion,, i't, appears to me t'~hat there is no proof that toba¢co<irnoke i's allergenic in man. It, appears likely that tobaeco~ smoke cer-; a inlY may he an irritant, and that it may contain components that are iinmunogenicine.xperimental animals. IN"hetheror not these corn- (>onentsare allergens is currently unknown. IThecu2•riculum~v.itae of D~r:Salvaggiomaybefound omp. 29$.] .1fr. JoNEs of North Carolina. Thank you very much, Doctor. The bells have just rung, and it is a vote which I think President t'arter is extremely intere sted in+-the veto override of' the. defensehu~lget. So, at thistime,,wewill take a10~minuterecess. • [lRecess taken,] ylir. JONES of1\Torth Carolina. Thesubcommittee wilt come to or- der,please. . We will continue -wit'li the hearing. The Chair is now happy to recognize Dr. Suzanne Knoebel from thcI~ncliana UniversitySchoollofMedicine.W'e are happy to have you with us, STATEMENT OF SUZ9 '-Tr r&NOEBEL, M.D., gRANNERT PROFES- SOR OF MEDIC1i;1:: ASSISTANT DEAN FOR RESEARCH, INDIANA UNIVERSt'1'Y SCHOOL OF MEDICINE, INDIANAPOLIS, IND. Dr. KrrOFnEr.. ThanP. you.>\'Ir.'Chairman. I am Dr. Suzanne B. KnoeheL of Indianapolis, Ind. I am currently t'11e Herman C. and Ellnora, P. hrannert ProfeSsorof Medicine and assistant dean for research at Indiana University School of iliedi- ~iole. In addition~ II am director of card'hovascnlar research at the, Vet- orans' admi>>i'stration Ilospital in Indi.anapolis. I am a 1960gr<<duatc~ of theIndiana University School of 'Medicine. .utd recein-ed postgraduatle training at Indiana. I ain al member of Alpha Omega Alpha Honorary.-Medical Society and Sig-rna Xi Hon- orarv Society for Scient~ificAdvancement.
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50 I am a member of many scientific societies including the American College of Cardiology, the Council on Clinical Cardiology of the Annerican~ Heart Association, andi the Association: of University Cardiologists. I am the author of over 100 scientific publications in U.S. and inter- national scientific journals: Prese.ntly; I serve on thc editorial board of the American Journal of Cardiology and Circulation. I have served on numerous review committees for t'he National Heart, Li:.ng, and Blood Institute. At present, I am a member of Resear& Review Committee A of the NHLI3I. My particular expert'iselies in the area of coronargheart'disease. You have myfulll curriculum vitae and list of publications. I' have been asked to discuss the issue of' so-called "passive smoking," that is, the inhalation of cigarette smoke by the nonsmoker andl its rela- tionship, if any, to cardiovascular disease. This raises the following questions: Can, tobacco smoke in the at'mospherecause or accelerate cardiovascular disease in the nonsmoker? And, can at'mospheric tobacco smoke exacerbatle preexistent, cardiovascular disease in the nonsmoker ?As to disease causation~ in humans, the first question is whether atmospheric tobacco smoke causes or accelerates atherosclerosis-so- called hardening of t'hearteries-in nonsmokers. Atherosclerosis is statistically associated with many factors: such as genetic background, psychological profiles; diet, and high blood: pressure. However, the etiologti and pathogenesis of this disease are currently unknown, and'it is unlikely that a single factor will prove to have any overwhelming, etiological significance: A limited number ofanimall studies have suggested that carbon monoxide, which isa constituent of tobacco smoke, might cause or accelerate atherosclerosis. A"otableamongthese are studies by Astrup., etall,, which reported higher cholesterol levels in animals exposed to carbon monoxide than in animals not' exposed to it. They also reported arterial lesions compatible wi'thearly atheroselerosis in the, . exposed group. However, other animal studies havee reported opposite, findings. And, veryrecently,, Astrup and coworkers have reported an inability to repeat their previous work. In commenting upon this netirst'udy, Dr. Astlrupstated t'hat "ap- plying the generally accepted criterion for intimal damage [that is,. damage to the coronary arteries] no direct toxic effect of CO can be demonstrated." Relevant to nicotine, animall studies by Fisher et al. using realistic amounts of nicotine for the srrnokercomparable to smoking 11/2 packs, of cigarettesa day, reporbed' noeffcct on the atherosclerotic procesa: Th~islh.•el of nicotineir far greaterthan the amount of nicotine a~ nonsmoker might absorb from the atmosphere. I would like, to point out that the. results of such studies cannot necessarily be appliedi to the human situat'ion. Experimental animal stndiesshould beviewed as contributingextremely important infor- mation on possible:areasof concer•ni and, even more, . importantlv, on basie mechanisms, of disease in order that meanin„ ful relationships can be pursued. As such, the.v necessarily have to be eltreic~ielywel2 controlled with only a single variable and, often, the.levclsof tlie fac.tor rnated Wit. levels The ;it mosl rarbor ]evels condit per m I lealtl -lloua The nonsrr c•ombi: rMmbil tionsI le\-.els t o be.l hare . in th( It 11 carcliff) "Theref rom,inalv: iiicoti aniy al To, tobac< hon n~ssin~ ~ ~pos incidlc It ' that : Pase. rlot ecl than 1 nvest tobac, mi~h Ia ltias n. in cir reacti A'r( ('onol Iia~ ai ihr r Is
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merican ~ of the iiversity I t ~d inter- oard of !r atiional!nber of xpert,ise ~iculmr ioking," its rela- il!lowing scelerate Dspheric ,inthe whether ~sis ~~-so- ,rosis~ is 'ground, ver, the wn,, and helhning earbon ,ause or ,Astrup.. )osed to eported esposed indi ngs. ,nability ~zat "a.p- [that is,, ' can be realistic /2 packs process. cotme a s~ cannott aniimal tt infor- ntly, on ionships ely~ well > of' the 51 f,«stor can be studied; that is, nicotine or carbon monoxide are accen- tuated in ordertha-t'stat'~isticallysignif'icant results can be obtained. With thisin mind, itis pertinent to consider what might be realistic li~~olsof t!obaccosmokeingredients that nonsmokers could achieve. 1'here, have been numerous studies on carbonmonosidelevels in the ,11niospliere from smoking. These studies indicatethate theaverage Canl,on monohide1eve1 is! 10 parts per million or less, even though lr%-els as h~igh as 42 parts permillion~ have been reported under seti-ere.011(litions. All' of these levels, however, are well within the 50 parts J)er million of carbon monoxideset by theLi.S'. Occupational and Ifra~ltli Administration as the li'mit for occupational elposureoveran --liourperiod. "I'herehave also been many studies on carboxz-hemoglbbin levels in rronsmol:ers exposed to tobaccosmoke.Carboxyhemoglobin is the 1,onibination formed by carbon monoxid'e and redblood pigment. The ~(Qnbined results of thesestudies indilcate that under realisticcondi- t ions and for periods greater than 60 minutes, carbozyhemoglobin I~ l~l in nonsmokerswill rarelveviceed ?'.to3,pereent. Ihai-.enoreason r~ofieliea°ethat these levels of carbolvhemoblobin saturation would iWnVeadverse cardiovascular consequeneesinterms of causing di'seasein tfie nonsmoker. Ithas long been recognized that nicot'~ine.strongly affects certain Cardiac functions in smokers such as heart rate and blood pressure.['Ihcreare, sonlestudies on atmospheric leNTe]'s of nicotine resultingh ronn cigarettesmoking, and the data are, complex. Hereagain, my,1n;tlvsis is that there is no reason to believe that t'~heamounts of nicotinea nonsmoker might absorbfromithe atmosphere would have nnr adversecardiovasculn.r consequences in terms of causing disease. To my knoavlecdge, thereare no statistical studies suggestingthattoba«co: smoke orany of its constituents. including particularly car- hon monoxide and nicotine, causes or accelerates theatherogenicproc- <-slin nonsmokers. In4act. it hasbeen sliownthat R-orkerschronicallP exposed toelevated levels, of carbon monoside do not haweal highenirio.idence of atherosclerotic disease than the general populationL It'~has been reported that cigarette smoke contains an allergen that might contribute to thed'evelopment of coronary arterydis- e.rse. Youi heard that from the lastit speaker. Hlowever, it should be notled that this report,n•.hich is based, on test'tube observations rather than live animal experimentation,has not been confirined by other iiln•.estigator5. Therefore, the question is whether the inhalation of tobacco smoke by nonsmokers results in t-hetype of react'ionthat mo--}ht lhaditoeoronary.arters disease. I am notan exper.tin this field~ bnt it, is my understanding that it has not been established that the reported allergen is actito.ally present in cigarette, smoke or that,if it'i6 present, it resttlt'~s! in a detrimental reartionin huinans.Fronl.my revienrof the pertinent animal and human data, I have to~ rouc]udethab, one, it. is not proven that atmospheric tobaccosmokeli€is an etiolo(Tical'rolein atherosclerosis in the nensrriaker; and, two, the ratibnale~for lnountinbstudies designed to: demonstrate such a <<istal role in~the human would besoNveak asto~beconsiKlpred! frivolbus. I shalll now turn totliequestion of whether atmospheric tobacco
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52 smoke can exacerbate preexistent cardiovascular disease in the non- smolker. Beforegetlt'ingintothis area, I would lhket'o digress for al few moments in order to establish some principles of cardiac physiology, as related! tlo coronary artery disease. Much of what I will say~ isover- simplified, but it should provid'e a framework for our common understanding. Under resting conditions, the heart extracts a high and relativelvy fiaed; percentage of the oxygen delivered to~ it in the, biood! via the coronary arteries. Because a significant increase in extraction of oxv- g'en is not possible,, increased demands for oxygen must be met byY increases in blood flow. But the presence of significant atheroscleroticc obstructive lesions in the coronaryy arteries prevents an increase in blood flow-the degree of impairment being dependent on the severity of the disease: Also, a decrease&oxygen~earrving capacity of the blood, such as caused by the formation of carboxy,hemoglbbin,, would result in an earlier requirement for increased flow.It is, convenient and graphic to combine the factors determining whether the heart will become ischemic-the state of inadequate oxygen-as a suppIy/demand ratio. AV, e can: then look at those factors that influence the rati&either favorably oradversely: The chief fac- tors, influencing demand are: One, heart'rate; two, how vigorousl1v the heart sqtteezes-its contractilfity;, three, the pressure the heart must generate to eject the blood into the rest, of the body; and, four, the size of the heart at the beginning of its work. The major factors influencing supply are: One, oxygen-carrving ca- pacity of thebiood!; two, heart rate;,three, blood pressure; and, four, the amount of atherosc.lerotic disease. If a patient with coronary arter.ydiseasewas exposed! to substances which, one, increased heart rate; or, two, decreased the oxy.gen-carry- ing capacity of the blood; or,,three, increased blood pressure or heart size; or,, four, increased cont'ractility. ;the supply/demand ratio~ could decl'ine and ischemia might result. However, the occurrence of ischemia varies considerably, almostindivi'dually, depending on the severity of the person's disease: The question here is what effects, if' any, do at'mospheric tobacco smoke constituents, particularlvy carbon monoxide, have on these sup- ply/demand factors in nonsmokers with preexistent cardiovascular d7sease?Unfortunately, there arevery few studies, in this area and, therefore, firm conclusions eannot bereached at this time. Data from studies using either pure carbon monoxid'e or actual smoking,are often difficult't~o interpret. For example, Ayres and co- workers showed that an acute rise in venouscarhox~-hemoglbbin to levels of 8', percent or greater, induced byinhalation of pure carbon monoxide, in four patients with coronary heart disease resulted in evidence of ischemia by the production of lactate. However, a sub- seqnentstudvbythesame group, ini which; etarboxyhemoglobin eleva- tion wasproduced by moregradual exposure to 1,000 parts per million of carbon monoxide for £3 to 15 minutes, did not show significant variation in lactat'e extraction in the three patients who breathed the lower concentration of carbonmonoiide over albnger period of time. In 1974, Dr. Aronow studied cigarette smoking and carbon monoxide breathivlgin eight patient~swith coronary artery disease. Pure carbon monoxide was delivered by mask but carboxyliemoglbbin levels n-ere ~ ~ ~ ~ : not that inde leve T som reso inde T und, carb can1 capt, reSu supl C1 for t been pres, theo, t~ient A~ etcei carb, box v coro31 of ca ]tnox+ Tt lie e n 10 p to th i Qicre and decre exerc Sir i>at ie a;•e perce Th tobeo sInnk "e.,n1i efilect Th, ll .1m t 'erta 1Mfor data . < mav in pai
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j thenon- j f'or a few hysiology. q is over- common ~ relatively /d via the. ~ n of oxS-- e met hyy osclerobic ;icrease in ~e severity the blood,, ktl& resultiermining kadequate isefactorschsef fac- yorously (theheart. 1, four, the, rrying ca- ~nd'y four,, I'~ubstances ~en-carry- e or heart fttio could ischemia ~ severityy c tobacco hese sup- ovascular area and,, or actual ss and co- Pglobin to re carbon ,sttlted! in er, a sub- bin eleva- er million ignificant atihed the 1: of time. monoxid'e re carbon vel~ were not given in the published results of that study. The study reported that "pure" carbon monoxide inhalation resulted i¢i a d'ecreased stroke index, a measure of contractility, while comparable ca.rboxyhemoglobin levels attained by smoking,d7d not resultin a d'ecreased stroke index. This raises, in addition to questions of application to smoking of~ some "pure" carbon monoxide observations, a problem, presently un- resolved,, of how to interpret the significance of a decrease. in stroke iiidex. The effects of carbon monoxide are highly complex, and until further understandiQig and quantitative data are available on theeffect's of carbon monoxide on myocardial function, levels of'carboxyhemogloliin (~annot be equated to a strict.lyy adverse effect on oxygen-carrying ~ apacity. This is because asinntltaneous deereasein contractility might >>esult in aloaver oxygen demand wh,ich n ould beneficially affect tliesupply/'demand ratio. Clinically, contractility decreasing agents are used almost routinely for the therapy of coronary artery disease. Carbon monoxide has also been shown to induce vasodilationi «ith, a secondary effect on filling, pressure of the heart and lower stroke volume, all of which, again tlteoretically; could actually be beneficial to certain subgroups of pa- t ie ntls with coronary artery disease. As noted above, carboayhemoglobin levels in nonsmokers will rarely exceed 2 to 3 percent. Assuming that nonsmokers, can reach levels of carboxyhemoglobin of 3 percent, what effect, can this, amount of car- hoxyhemoglobin have on myocardial oxygenation in thepatients with ceoronaryartery disease?Unfort:unatel~y; due to the complex naturee of'earbort monoxide effects, the answer to this~question is not currently llnown. The onlyy study in which patientswit4 coronary artery disease have been exposed to atmospheric tobacco smoke is a very recent study of 10 patients by Dr. Aronow. It was reported that patients exposed to thesmokcof 15 c.igarettes,withfin 2' hours~ in a well-ventilated room increased resting heart rates, systolic and diastolic blood pressures, and venous carboxyhemoglobin to an av.erageof1.77percent, and decreased heart rate and systolic blood presstire required to produce ;ingina-the chest pains secondrary to coronary artery disease-with exercise. Similar direct'ional, changes of greater magnitude were observed ini patientlswith similir exposure but in an unventilated room~ The aver- a,Te carboxyhemoglobin level in theunventil'ated room was 228'8 percent. The changes in blood pressureand heart rate at rest were presumed to be duetoabsorht'ion of nieotineby exposuretoatmosphericcigaret't'esrnoke: The reporte& decrease in blood pressure and heart rate which restilted in angina was presumed to be due to the carboxyhemoglobin efifect, on oxygen availabilhty, thus decre'asing the supply/demand ratio. There are problems~ wi'tlr the experimental design of this study. I am not, here to crit'icizeit; it mavultitrnately be proven to be correct. Certaidily, conGrmation is needed in a, much l'arger patient, population lefore accepting the validity of the findings. ?1liy role is to assess the Ilata as to whether or not thcv indicate that-atmospherictobaccosnoke mayeausedetrimental effectsin patients with cardiovascular disease, in particular, coronary artery disease.
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54 Quant'itative considerations lead to the recognition that the heart rate and blood pressure alterations reported in Dr. Aronow's study were very minimal. The maximum heart, rate change was 7.1 beats per minute in the patients exposed to smoke in an unventilated room. The maximum systolic blood pressure change was 7.6 milligrams Hg. It can be stated without equivocation that the likelihood that such chanbes woul'cll adverselyaffec.t a patient with coronary artery disease would be infidliitesimal except if the patients -wereseverely ill and had associated factors such, as anemia. GY'eatler heart rate and blood pressure changes than those reported by Dr. Aronow may occur in response to normal physiological control mechanisms as well as ini response to minimal activity. Considerably greater changes may occur with emotional stimuli. In my personal view, studies such, as those mentioned should be pursed in a qttantitativefashion. Theend point for an adverse effect should be the demonstration of actual ischemia, not simpiyy the poten- tial for ischexn2a, and the studies would need to be done for graded severity of disease. My prediction would be that inhalation of tobacco smokee under rea1- istic conditions will not prov.oke ischemia in patient.s with coronary artery diseasea~t rest, particularly when the emotionali impact of fear ofi tobacco smoke is removed. This is not to savt,haty under certain con- di't,ions, there are not some who are so extremeiyv ill that they might develop iseheiniai. As to the possible reduction in exercise tolerance from increased ca~rbonmonoxide levels, I can only say that,in myy opinion, it is yet to be determined under«hat'circumstances this mightbedetrimne.ntalt to patients.vit-h coronary arteryy disease. In, conclusion, t.hereareno indieationsthat tobaccosmoke, ini t1heat- mosphereeithercauses or accelerates cardiiovascular disease in, the healthy nonsmoker. Nor do av.ailable studies establish that atmos- pheric tobacco smoke under realistic conditions, adversely affects non- smokers with preexistent cardiovascular disease. However, more re- search is needed in this area. FThe curriculum vitae of Dr. Knoebel mayy be found on p. 322.]j Mr. JoxEs of North, Carolina. Thank you v ery muc.h, Doctor. Are there any questions from the members of the subcommittee ?' Mr. Wampler. Mr. WAMPLnn. Thank yony Mr. Chairman. Dr. Knoebel, in discussing Dr: Aronow's study, you talk about the emotional impact of fear of'tobaceosmoke.Can thisfearcausepeople with heart diseaseta egperiencepain painKNoERFL. Well, it has not been demonstrated scientifically, but itt could, byt.he increase, in heart rate and blood pressure that accom- pany fear which were mentioned earlier. This could c.auseincreased demand from the heart, and', theoreticalls, it possibly could-yes.,llr. IVnarLEx. I certainly wantt to thank you for a~ very compre- hensive statement thismorning. We appreciate your presence, and we part;icularlyappreciate your patience in bearinqwith the sub+ committee. Mr. JONES of North Carolina. Mr. Whitley?' Mr. titi~~ FiiTLEY. Mr. Chairman, I have one question. Dr. Knoebel, as I understand your testimony, carbon monoxide might, undercertain circumstances, bebeneficial to persons with heart disea, Nchicl Dr have facto E>oint ox v(; 1indcMi stud` thev` Dr Ml JfI ~•our . ~ n t :ulal` ['I
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55 ie heart s study 1 beats iltilated! ligrams od'~ that ~ arteryy geverely i !eported i control ;derably i jpwld bese effectt e poten- I'graded ler real'- oronary, ; of fear ain con- 'Y mig ht lerance , in my s might the at- ~ ini the atmos- ~Cts non- pore re- I tee? Mr. bout the e people a11y, but t' accom- ricreased -yes. compre- , and we ;he. sub- ionoxide ith heart disease. How do you reconcile this view with Dr. Aronow's studies which have been recentl~reported ini the press~?Dr. K-NoEBEr,. Well, I t.hinkI have stated that the end! point would have to be t'hedemonstratinn of ischemia by the supply/demand factors that I mentioned. Dr. Aronow's study used! al subjective end point. If you have a decreased contractility; this would decrease the oxygen demand for the heart. Theoretically, this might be beneficial under conditions where an increased' cont'ractility was causing angiuaa. Mr. WHtrrLEY. So, the mere fact that the 10 people in Dr. Aronow's study experienced certain physiological changes does not mean that, they experienced any harmf'ulleffects?Dr. KN.oEBEL: Correct. Mr. WHITLEY. Thank you. Mr. JotiFs of North Carolina. Thank y.ou very much, Doctor, for your appearance here this morning. Our next witness is Dr. Sherwin J. Feinhandler, a social systemsanaly,st, of Watertown, Mas.s. [The prepared statement submitted by Dr. Feinhandler follows:]
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56 S,J,,Feinhandler, Ph.D6 STATEMENT OF'SHERWIN J. FEINHANDLER, Ph.D I am Dr. Sherwim J~. Feinhandler, a Cultural Anthropol- ogist. I have studied at London Universi'ty and hol!d' degrees from the departments of Sociology at Northwestern University, Anthro- pology at Syracuse University, and Social Relations at Harvard University. I am presently a Lecturer in Anthropology in the Department of Psychiatry at Harvard Medical School and Director of Social Systems Analysts, a social and behavioral science research firm in katertowni, Massachusetts. My research interests include the structure and culiture of community life, and I have published various articles and presented papers at professional meetings in these areas. I have been a consultant for federal, state andiloc- al government agencies as well as educational and private organ- i4ations. Among my interests is tobacco and its place in society. I shall speak on the soci'a1i and cultural meanings of smoking, the interpretation of the anti-smoking, movement and is- sues concerning the regulation of behavior. Throughout the world today there is almost no society that does not have andi use tobacco. Agricultural tribes in Africa cultivate it and nomadic tribes trade for it. It is grown in gar- dens by Pacific Islanders, andi is now found wild in New Guinea. Asia and the Middle East are well known for growing tobacco. In almost every society, from the most simplie to the most sophisticated, tobacco figures prominently in the social and/or ceremonial lives of the people. For example, it is used in Pac- ific Island courtship rituals; in African councils, clan gather- ings and marriage negotiations; in North and South American Indian divination an& healing ceremonies; to seal bargains in Asia; and f'or hospitality in the Middle East. It is important to remember that tne history of smoking in western civilization incluoes many ups ano downs that are tne res- ult of, fasnion. Throughout history there nave been attempts to S_ ret tu. dul ki.i foi to: it~ peC' elo yez soc pho des bee puS cor seeE anc qui ref agc in cig ing has fro~ smo to1 the anx page 1
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57 ~ ~ I I Ithropol- ees from Anthro- Harvard r in the ector of research include lublished Itings in and loc- ;e organ- ,;society. ings of and is- S.J. $einhandler, Ph.D. regulate the use of tobacco. For example, in the Eighteenth Cen- tury a Turkish sultan cut off the lips of smokers and an Austrian duke put smokers in prison. In the Seventeenth Century an English king wrote tracts insulting those who smoked, taxing them heaviliy for his own benefit. Smoking in this country went out of fashion in the middle to late 19th century, a time when ideas of Victorian respectabill- ity held sway. During that period' smoking was associated with people of low social position. The middl'e cliass, forming and dev- el'~oping, wanted'no association,with this behavior. Less than 100 years before, smoking had been a mark of good breeding and high social status. Attitudes toward tobacco have again undergone a metamor- phosis in recent years. Folilowing lvorld War I1I, it was socially desirable to smoke. In the past decade, however, the smoker has been subjected to a variety of attacks. Anti!-smoking critics im- pugn the smoker's sense of responsibilfty to others, denigrate his concept of self, accuse him or her of discourtesy, and, in short, seek to humiliate and shame. Anti-smoking crusaders bombard the smoker with warnings and admonitions. "Protectors", convinced that the smoker should quit, have accelerated their efforts. This militant crusade to reform tne smoker has sometimes taken on a tone of hostility and aggression. Bewilderedi smokers are doused with water and sprayed in the face. They have lemonade poured over their heads. Their cigarettes are sheare&off with scissors. The battle-cry of anti-smoKing forces is "stamp out smok- ing". To some people the smoker nimself is an annoyance. These hostile confrontations point to an antagonism that possibly stems from basic differences in life-style between the nonsmoker and the smoker. Encounters between them are on a very personal level and tollerance of differences seems fast slipping away. To some people the smoker has become a ready target for general frustrati!ons, anxiety ano discontent. page 2
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58 S.J. Feinhanoler, Ph.D. Society has suffered enormous upheavals in the past dec- ade, and those tremors are still being felt. The phenomenon of anti-smoking fervor is, in part, a result of those changes. Individual's and groups in alli societies feel a need to es- tablish boundaries around themselves, a buffer zone apart from the larger society. Individual expression, however, is hard to ach- ieve in a highly mechanized society; identity becomes obscured easily. In recent years people have been involved in a process of turning ihwardi. For example, note the rise of EST, transcendental meditationy encounter groups and the focus on individual identity. For the nonsmoker, the physical boundary may take the form of nonsmoking sections in trains, planes, buses, taxicabs, public buildings, restaurants,, elevators, etc. On the symbolic level the smoker is seen as an invader, a poliluter of the personal space of the anti~-smoker. However, it is important to distinguish between nonsmokers and anti-smokers. Not all nonsmokers are against smoking. Furthermore, the anti-smoker infers a variety of motives and defects about the smoker: he is inconsiderate and has a weak character. The smoke creates the boundary, andithe smoking symbol- izes these perceived characteristics. Under such circumstances, tolerance falls to a low ebb; and that is presently the case in this country. The smoker with his visiblie smoke is an easy target for venting frustration. In the minds of anti-smokers, the smoke may even be equated with physical' assaulit. Convinced that their health is endangered', they feel the urge to "fight back", often responding with aggressive, hostile acts. A moral fervor underlies anti-smoking efforts. A linger- ing puritanism in American life equates pleasure with moral is- sues, and customs such as smoking, appear "moralLy wrong". Thus, the zeal of anti-smoking leaders has led them to be called "moral entrepreneurs".1 A Manhattan psychiatrist has even suggested that it is a struggle between the perceived machismo of the smoker and the puritan impulses of the reformer.2 The reformer sees tne smoker as powerless to escape the negative influences in which he is enmesneo and, therefore, must save him. i hel The qua kno, our wor. Sinc the have near autc as t move four thei burd or p latil has clas Smok ers stat i'a1l . page s
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59 t dec- Fion of I'i 'to es- lom the o ach- iscured tess of idental' intitye ie form 'publ ic rel the race of >etween tgainst notives 'a weak symbol- Cances, tase in target smoke their often linger- fal is- Thus, "moral ed that ker and ;es tne nicn he Also at work is a need'to assign blame and to enlist those held responsible for problems in eff'orts to alleviate them. There is a recognition of the relationship of pollution to the quality of life. Industrial effluents and auto emissions are known violators of our space, but direct control is taken out of our hands. This reforming culture holds society at fault, but the world of institutions and government and industry is amorphous. Since the individual cannot confront the real source of anxiety,, the smoker is the ready target for the blame for "pollution". 1 have several acquaintances who eschew smoking! but jog regularly near roads along the Charles River, one of the areas of highest auto emi'ssiom in Metropolitan Bostom. They are hyperventiliating, as they suck hydrocarbons and carbon monoxide into their lungs. The parallel between the anti-smoking and Prohibition oovements in this country is unavoidable. The parallel can be found in the moral fervor; the idea of protecting people from their own defects; the idea of social costs, work los't, children a burden to society,; and the idea of the offense to public decency or publiic comfort. Just as in Prohibition the target of anti-smoking legis- lation often turns out to be the working class and the poor. It has been reported that smoking,is more prevalent among the working class3 and that over 90% of persons appearing in the Chicago Smoker's Court are black.4 The ultimate goal of anti-smoking,g;roups is stopping smok- ers from smoking alitogether. They have not been reticent about stating that their main weapon i'n forcing,smokers to quit is soc- ial control. An American Lung,Association spokesperson has said: Probably the only way we can win a substantial red- uction (in smoking) is if we can somehow make it non-acceptable socially..... We thought the scare of medical statistics and opinions would produce a major reduction. It didn"t.5' Smokers are made to feel dirty and unattractive with such Slogans as, "Kissing a smoker is like licking a dirty ashtray." page 4 ge 3
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60 S'.J. Feinhandler, PhsD. They are made to feel guilty by leaflets which proclaim, in bold type: "How Not to Love Your Children." Anti-smoking group acro- nyms reflect the negativism: ASH (Action on Smoking and Health) and GASP (Group Against Smokers' Pollwtion). SMASH:, in Issaquah, Washington, is an acronym for Society for F1©rtificatiom and Smoker Humiliation. They have publidshed a manual of Drastic and Mortify- ingly Nasty (DAMN) Countermeasures.6 Cessation clinics dot the country offering group therapy. The goal for all is the one pro- claimed by the American Cancer Society: to move, as rapidly as possible, toward a nonsmoking society. A "health hazard! to nonsmokers" theme runs through the anti-smoking campaigns. Yet, there is no proof that tobacco smoke is harmful to the nonsmoker, according to notablie experts on both sides of the smoking controversy.7 ' In a major study, of the ef- fects of smoke oninonsmokers, publi:shed in the New England Journal of Medicine, Harvard University researchers observeo that: it is important to keep in mind the distinc-tion between health effects and annoyance. Unpleasant odors may be very annoying but have very little ef- fect on health except on,a psychogenic basis. It seems likely that irritating gases, unpleasant odors, peak concentrations, and high visibility play a part in the annoyance reaction to tobacco smoke.d ... Anti-smoking groups have won over nonsmokers with talk of rights and healith hazards and their concerted effort to turn the tide of public opinion against the smoker. They have drawn gov- ernment into the effort as wel~l, and public smoking legi'sliation is being enacted at the federal, state and local levels. Increasingr ly, legislation is being substituted for tolerance in,the struggle to maintain individual freedoms. During a conferencd in Munich on the medi'cal and 1'egaL aspects of smoking in the work place, the Director of the Bavartan State Ministry of Labour and Social Oroer brought up this issues: page 5 S.J. Fe ears ag .a1s wit r.ac rec '•as ceutl 34-12I,o.
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in bold~ p acro- tlealth) ~ Isaquah, ( Smoker (ortify- dot the ine pro- idly as ugh the ~o smoke on both the ef- Journal talk of turn the pwn. gov- ati!on is reasing- struggle unich on ace, the al Oroer )age V 61' S.J. Feinhandler, Ph.D. Tolerance towards the needs, lifestyles and opin- ions of others is a basic, indispensable prerequ- isite for a11 sectors of human coexistence. With- out tolerance, it is not possible to strike a sat- isfactory balance of mutual interests in the tense atmosphere between smokers and nonsmokers.9 As an astute editorial writer has observed: A little good will and some good manners will go farther toward solving mutual problems than givi'ng one side a legal club to beat on the other side.l0 There are serious issues concerning public smoking and government liegislation. In a society where tensions and anxieties give rise to anger and frustration, there is always a danger in aUlowing pressure groups to influence legislation restricting ind- >.vid'ua1 freedoms simply to alleviate annoyances to another segment of society. In times of high tensiom and anger it is incumbent upon government to move with caution and deliberation. In the smoking aebate government seems to have chosen sides in the clash over rights, and appears to support social controli efforts. Smokers may suffer fines, arrests, harassment and humiliation at the hands of enf'orcement authorities, for pursuing a particular personal life- sty,1e. With the widespread enactment of public smoking bans, res- tricti'ons on smokers reach into: alimost every, area of their liives. Recently, the campaign has been taken to the workplace where peo- ple spend the bu1R of their time. There are few totally free areas left except, perhaps, the home. The central problem of democracy, as Tolstoy knew 100, years ago, is always the reconciliation of the claims of individ- uals with the claims of society. There is cause for concern when tnat reconciliation curtails personal freeooms. As one attorney ^as cautioneo: page b 34-1l1 0 '- 78 -5
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62 S-.J~. feinhandler, Ph.D. The tone of spontaneity of spirit that character- izes a free society cannot survive in an atmosphere where all deviations from the norm are immediately noted by the state and stored for future reference. The existence of the file itself is chil~li'mg, even if it is never used.ll In recent years, we have tended toward alQowing a person to pursue his personal life-style without fear of reprisal. 8ut an about-face is occurring with the passage of laws allowing the monitoring of daily activities. , Smoking is a ritual' that welcomes strangers, providest companionship in solitude, f'ills "empty" time, marks the signif- icance of certain kinds of occasions and' expresses individual id-1 entity and personal style. Thus, the campaigns designed to change the behavior of the smoker are aimed at modifying,a life-style. In reality, these efforts by a segment of the population serve to obscure the real problems in society. As a result, they make enemies of potential a1'lies and turn social issues into int- erpersonal ones. Ultimately they are doomed to backfire. It is a dangerous precedent for government to choose sides in debates over lifestyles and interpersonal struggles to estab- lish individual identity. There wi11i always be a conflict of rights. Individual'freedom is crucial, and we are reminded that: free choice remains the essence of a free society. Either one does what one wants--within limits pre- scribed by tradition and nei'ghborly pressure--or one does what government says. The more ordin- ances, the more government we have; the more gov- ernment, the less f~reedom.12 page / 1 2 3' 4 5 6 7 a 9 lu 11 12
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63 S.J:'Feinhandler, Ph.D. r pre fy 1 REFERENCES Becker, H. S. 1963 Outsiders: Studies in tne ;e. Sociology of Deviance. New York: Free Press. 2 Dunkell!, Samueli V. 1197tt Quoted in "Huffing Over All that Puffing". Time Magazine. April 24. a person 3 Sterling, T.D. 1976 "Smoking Characteristics by Type sal But of Employment." Journal of Occupational Medicine. . 1$('11). :owing the 4 Editorial, "Against the Smoking Ban". Amsterdam News. provides 5 New,York City:April 29, 197d. Sullivan, Ann. 1975 (quote from ALA spokesperson), :e signif- ,id al id- 'Lung,Group to Open Drive for Rights of Nonsmokers." , Portland Oregorian. May 14', 1975. u to change Reported in,"'The City Window." 1976 The Kansas City '-st le Magazine. August. y . 7' Hine C'.6. 1977 "Second-HandISmoke -- Is it Harmful?". >opulation , San Francisco Examiner. August 11. tult, they 'into int- b Hinds, W. C. and'M. W. Fi'rst. 1975 "Smoke and Heat". New England Journal' of Medicine. 293:47-4y,Ju1!y 3'. 9 Schmatz, H., "Passi've Smoking at the Workplace", in ~ose sides Passive Smoking at the Workplace, Bavarian Academy to estab- for Inoustrial ano Social Medicine, March 31-Apri1 1i, 11977, p. llb. nfLict of 101 Editorial "Don't Tread on Corns" west Virginia Mail led that: I !1 . , . Charleston:March 23', 1976. Neuborne, Burt. quoted imiS_aturday Review. April 17, 1971. 12 Murchison, Vtiilliam,. "Is There a Ri'gnt to Smoke?' ii Dallas Morning News. May 13, 1974. 5 page i '~/ page o
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[The curriculum vitae of Dr. Feinhandler may be found on~ p. 331.] DZr. Jorrrs of North Carolina. Thank you, Doctor, very much for your appearance here. I am certainly intrigued by your testimony and very grateful for it. Are there any questions from members of the subcommitt,ee,? If not, we wi111 go onL Thank you,, again, D'octor, ffor appearing here. Our next witness is Dr. ~'Valter M. Boo~er of Dr. Walter :lT. Booker & Associates here in Washington, D.C. Dr. Booker, the Chair is happy to recognize youL STATEMENT OF' WALTER M. BOOKER, PH. D., PRESIDENT, DR WALTER M. BOOKER & ASSOCIATES, WASHINGTON, D.C. Dr. BOOKER. Thank you very much,llLr. Chairman. I want to express my appreciation to you for the invitation and opportunity to, file a briefl stat'ement'and tocomment on it at thistime. Distinguished Members of Congress, my name is Walter M. Booker. I am a consultant pharmacologist. I am president,of Walter bI. Booker & Associates, an incorporated biomedical group here in the District of Columbia, I am also professor emeritus of pharmacology at Howard Univer- sity where I was chairman of the department of pharmacology for 20 years. My professional training, after earning a bachelor's degree from Morehouse Col'lege in Atlanta, Ga., consists of a master's degree in cellular physiology and biochemistry from the Univ.ersity of Iowa and a Ph. D. in physiology and pharmacologyy from the University of Chicago. I also had the distinction ofenjoying,apostgraduat'eyear asasenior Fulbright scholar in Belgium an& Sweden, studying with two Nobell laureates. I hold memberships in numerous scientific societies including the American Society of Pharmacology and Experimental Therapeutics, the American Physiological Society, the American College of Clinical Pharmacology, and the American College of Cardiology of which I am a fellow, and I therefore have the privilege of adding FACC to the Ph.D. degree. The views I am expressing to you here, today are based upon my training and myy expe,rienceasa pharmacologist and as a scientific researcher. As a pharmacologist, mytraining, and experimental work have taught me to observe thephysiolo~xical reaction of an individual or ananirnal to a~ particular agent. While working with graduate and medical students, I was actively engaged in study,ingthepharmaco- logicall effect'sof' various substances in the experimental and clinical setting. Forexample; my experiments with nicotine focused on various physiological ll parameters such as blood pressure, heart rate, and car- diac contractile force in animals and in man. lTuch of my experimental nicotine work was reportedl upon at scientific meetings and wassub• sequentl,yy publishe& in the literature in the United States and abroad. One of health of i)11CCo smo. 1,avemea: -1noke. F4 f IIamburg tlieskin t, Of both a rnental ro of Passii-.( Tlie pu. <how biol hacco sm~ '.,lood pr, liarametewas no d (~ x posure This latt+ ~elrcherss measure c In the only a ve bti• the no A toba ~4inoker i! which ha Russe.ll a~ hemogloll }xiccosm\ onFmol• 'I'ohaccoHarke nonsmokProblem 1970.) HoR-e` Smoking levels-ll R. D. St, Blood D of 1974.) . Pe.rha kowski ( measure( ~nlokers1 oxide Fi mean:va ol~w., the ~1dded b( As noo research, sinoker lilost erl
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i t p. 331.] nuch for nony and ;? If not, e. 1. Booker ~: Booker. f. Booker 4 District I Univer- plogy for i ~ree from egree iniIowa and rersity of ~ ading the rapeutics, ;f Clinical of which ig FACC upon my scientific iork have lvidual or Juate and )harinaco- Ld clinical n various. ;; and car- >erimental ;1 t was sub- id abroad. 65 One of the majpr questions we are add4-essing todayy is whether the health of the nonsmoker is adversely affected by environmental to- bacco, smoke. In this regard, there have been a number of studies which have measured t'hephysiological reactions of nonsmokers to tobacco smoke. For example, an important study in this area was done in I iamburg, Germany, by Harke and Bleichert in which they measured tlieskin temperature, the pulse rate, the EKG, and the blood pressure of both~ active smokers and nonsmokers located in the same experi'- mental room. (This is from Harke and Bleichert's "On the Problem of Passive Smoking," in the Int. ArchL Arbcitsmed. of 1972.) The purposeof the experiment was to ascertain whether nonsmokers ~,hoiv bi'ologically determinable effects when exposed to ambient to- bacco smoke generated by act.ivesmoking. Measurement's, of~ EKG, hlood pressure, and pulse frequency revealed that none of these lparameters was significantly altered in nonsmokers. Moreover, there Was no decrease in the skin temperature of nonsmokers even after exposure to extremeliy= heavyy smoking for approximately 2 hours. This latter result was viewed as a highly important one by the re- ~:e lrchers because skin temperature is thought to be the most sensitive measure of the physiological effects of nicotine. In the light of these observed physiological effects, it appears that only- a very small amount of tobacco smoke could have been absorbed' hy the nonsmoker. V tobacco: smoke constituent often mentioned in regard to the non- sinoker is carbon monoxid'e-CO. There have been numerous studies NN-hich have measured CO intake in both simulated and real situations. IRnssell and others have shown an increase in blood level of carboxy- liemoglobin-COHb-to 2.6 percent in nonsmokers exposed to to- hacco smoke in a nonventilated room. (This is from~ "'Absorption by V`onsmokers of Carbon Monoxi'deFrom Boomi Air Polluted by 'I'olonecoSmoke, in the 1973 edition of Lancet.)I+Iarke has also obsenved an elevation of carboxyhemoglobin inthennnsmoker to 2.1 percent in an unventilated room: (This is from "The Problem of Passive Smoking," in Munch. Med. Wochenschr. of 1974.) However, when, ventilationi was introduced, t'lieCOHbllevels of non- 1~moking subjects remained well within the range of averageCOHble1'els-1.6 pe,rcent-foundin the U.S. population. (This is notedl byh. D. Stewart and others in "C'arboxyhemoglobin Levels in American, Wood Donors," in the Journal of the Americani Medical Association of 1J74.); I°e,rhaps the most relevant experiment has been conductedl by Szad- ko«ski et a]. At'the beginning, and at the end of the workday, they measured tke COHb of nonsmokers actually working in offices with `n1okers. (This is written up in the article, "Burden of Carbon Mon- o!+ideFromPassiveSmoking, in Offiees;"Inn. Med.1'i976J When thell1ean N-alues,of COHbinthe 130 nonsmokers decreased throughout.the. (I«v, the~ researchers concluded that the nonsmoker does not have an ,~rlded bodvburden from CO due topubl icsmoking: 1s noted earlier, nicotiroeabsorption has been studied bynnmeroush-earchers. The obvious question is how much nicotine does a non- `Iljoker absorb when exposed to realistic levels of tobaceosmoke? Klosterkotter addressed this question and concluded that a nonsmoker
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66 may absorb one one-thousandth of the amountof nicotine taken in ; by the smoker. (This was noted in the proceedings of a conference,' "Passive Smoking at the Workplace," in Munich, Germany, arranged' by the Bavarian Academy for Industrial and Social Medicine, Mareh~;: 31 to April 1, 1977.) Support for this measurement can~ be found inFi the published tests of nicotine in real life situations: Hinds and' First of H'arvard University, used nicotine as a: tracer' of the particulate phase when they measured tobacco smoke coneen-~ tration in various public places in and around Boston, Mass. (This is written up in "Concentrations of Nicotine and! Tobacco Smoke in= Public Places," from NEJM, 1975.) Based on their mea.surements,;, these scientists estimated that a nonsmoker can potentially inhale fromi one one-hundredth to one one-thousandth of a filter cigarette per hour. ~ Many of you may know about the recent study on heart patientstt whiehhas received media coverage,, and~ which was referred to bytwo~ or three of my predecessors here this morning. ~ This studyy by Dr: Aronow purports to answer the question of, whether angina patients are adversely affected by exposure to tobacco smoke. Unfortunately, this study fails to do so because of several serious deficiencies. First, the author does not present' the data that allows,one to reach conclusions about certain changes in physiological parameters. Dr. _ Aronow did not measure carbon monoxid'e or nicotine levels in the; experimental rooms~or nicotine absorption in the anginal patients. Some ~ of my predecessors have gone into great detail on that point and I will . not take your time discussing it further. Second, it is difficult to gage the effects of psy chological' stress on. the outcome of the experiment. That article has paid very little atten-' tion: to the psychologicat stressinvolbed in sitting in a small room for~. a period of 2 hours with nothing to do. Psychological factors may have * even affected the results t'o a point that they are not reliable. Third, the experiment was noti' "blind," and a reader must wonder' why this technique was~not used and consider the possible introdtiction' of bias. I.vould like to emphasize this by saying that Dr. Aronow and thcother medical personnel whotested'thesubjects in t.hisexperiment#s kneww exactly from which room every subject came-that is, whether or not the patient had been exposed to t'obacco smoke. There was ab- solutely solnt'ely no blindness intliis study. Finally, due to its limited scope; the result's of the experinaent can-1 not be generalized to larger populia.tions. In this regard, Dr. Aronow : has tll d b ~ apparen -ma e pu lic statements tht hiklietilli jas~worapps~o mons of people. . IVhen I seeresearchfindi'ngs extendedi in thiswayy gentlemen,my, experience as a scientist ]eadsmeto question both, the motives of the;authore and the meaning of thee experiment. Wllen dealfing with an issue like public smoking who,ch~ has strong ~emotic,nn1l overtone.s, it is unportrinf to lc^-y those factual data ir, mind.. Earlier this Veair; aii ellun;^nt Gerloan scienti-4 madeastat~emen[ that seems to fo11e%v tl-.:, riilh. Dr. G. Lclmert, president of the German Society for3ndustria1 Medicine, summarized the environmental to= bacco smoke issue in the folloaving manner : Passive smoking can certainl,4 lead to annoyances in some situations, such as for example, when there is insufficient ventilation. i I Scien smokim our knc Thi=. N-olum, As ~ wheth, ,dheth, I iterat absork 5inc oludin tunity i nvitir (Th Mr. 9ppea Are Mr:. Dr. the.sc and tl t~obenando. Dr. ~ampl the ir 'honl1 Mr. Mr. :;ide?Mr. Dr. tobac, smokE; Dr. Mr. Dr. ortot Mr stater Dr. Mr know tion t causelunten t his nrnm, W} Dr and :interc
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t4 as a trace? bke ooncent ~ss. (This.i? ' 1:4 > Smoke i asuremen inhale fro to per hour' ~Lrt patient~ ;d to byy tw r i i,question o ' e to tobacco f of' several i )ne to reacl: meters. Dr.% ~ve1S in the rrents. SomeY t'andIwill, i ;al, stress onr little atten " 01 room~ fof rs may hava# s ~:b1e knc1-_ mnnrla ntrodtictil kronow and experimene is, whethe~ ~ ` fere was ab-~ i iriment can= ~ Dr. Arono_4 s to million~ ~ttlemen, m~ itives of the;', has stron~ ata ir, mind. tementthat°; ,he German nmental W 67 Scientifically unequivocal and objective proof of harm to health from passive smoking has, however, not been produced to date for any population group, to mrr knowledge. This was noted in Arbeitsmedizin, Sozialmedizin,Praeve.ntimedizin, vohune278; of 1:97$. _~s a scientist, I am interested in reliable data which d'emonst'rabo adrckher a nonsmoker absorbs tobaceo smoke in public places andy if so, wlretlier theamount,, issufficient to cause adverse health effects. The ]iterature, in my opinion, d'oes not support the theory that a nonsmoker ;il,sorbs amounts which can cause liarmL tiince this statement isvirt'uallv a summary, I have no other con- (ilurling statement except to say that I am plieased to have the oppor- timi't)-y to bring these facts to your att'ention. I thank you very much for i nsitingine. ( Tlie c.urricul um vitae of Dr. Booker may be found on p. 337.]'I ltr. JONES of North Carolina. Thank you,, Dr. Booker, for your al)1)eananceherethis afternoon. Are there any questions of this witness ? Mr. Whitley. Mr. WHITLEY. Mr. Chairman, I have one question for Dr. Booker. I)r: Booker, is it not a fact that the most fundamental principle of tlle scientific, method! is that if one is going to study a small sample,rnrl then generalize from that sample back to the population, it has t(fre considered that you have to be very careful to draw a true nrnclom sample?I?r. BOOKER, That certainly is~ true. In addition, the fact that the ,ample is, very smalll ought tohave been one oft'helead statements in the introduct'ion to the paper. This, of course,, was not done. This -holtld have been regarded as only a preliminary study. Mr. IpxiTLEY. Thank you verymuchL Mr. JONES of North Carolina. Are there any questions from this 'irle?'M~r. Wampler. Mr. WA--NtPLER; Thank you, Mr. Chairman. Dr. Booker, other witnesses this morning referred to atmospheric tolmcco smoke. In your statement, you refer to environmental tobacco 'rnoke and then ambient t!obaccosmoke. Is there any great difference? Dr. I3ooxFR. No. They are essentially the same. Mir• WAarLr,n. It is virtuall,y the same thing? Dr. BooxEx: Yes-the exposure of an individual to an atmospheric Or to ambient smoke or to smoke in a room. ~j!r. ~V,~~zrr.Ex, I thank you, and I thank you for your excellent tatement. We appreciate your presence here verymuch: Dr. BOOKER. Thank you very much. ~fr: To-sES of Northi Carolina. Dr. Booker, recently, as you well kno~s-. Senator Kennedy, over ont'heotherside, introduced legisla- t i"n that wotild, in effect, restrict'smoking in Federal buildings be- Catlse.he said thatnonsmokershave aright to be protected' a,--ainst the1i-tentialJ liarrn, associated'with exposure to cigarette smoke. Of course, rl'is followed very shortly after Secretary Califano of HEW an- nnirnrerl his antlismok~ingcampaign. IN'habareyour views onithesestatements; Dr. Booker? Dr• BooKF~z, ~Vell, first of al14 I have great respect for the Senat'oramd for the Secretary. I read! their statements withi a great deal ofinterest„
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68 I see no reason .vhy Government buildings, per se,,should be sirngle&,. ` out. If tobacco smoking is harmful to the nonsmoker, it ought to a question of banning or not banning. I think, on the other hand, that the reason for the focus on Govern* g , p 1J p y olbgists,, of pathologists; of inen who are devoting their lives to study- In summary, I am troubled by such a move-a move without' suffi~ cient data. I would' hope that the two gentlemen would tend to slow" k down on this until we have had an opportunity here in the United' States to have a scientific forum of cardiolb ists of res imato h siJ spread this a little further on each subsequent move. ment buildings is to develop ai limited ban as an initial step and to"~ ing the things that we are talking about. I think it should be left i, their ha.nd§. Mr. JotiES of North Carolina. Thank you. Let me inject into the record at this point that the matlt'er we are just discussing, that, is, the introduction of legislation, is I'lie~ very. , reason for this hearing today. Those of' us who are attempting to~ba~ fair and impartiall and deal' with fact's, and not emotions, readize thati I hope we can cool off those who would save us from ourselves bef'ore there must be another side, and the jury is still out. they get too far gone. Dr. BoofiFn. 11Zr. Chairman, your statement is very much along the'! line that I int'endedtlo close with, but because of time I thought I, ~ would cut it short. Whale, sitting in the room al few momentsago; I sta.rtedt'o say;~ "WelL the jury is still out," but, since I hav~ebeenin'courts of law as ; an expert witness in various me.dical/legal situations, I do not think thattheevidencehasbeenpresentedyet.. [Applause.] Mr. Jo` rs of', N orth Carolina. Thank you, Doctor. Our last witness is Mr. Reuben Cohen, president of Response Analy- sis Cbrp., Princeton, N.J. [The prepared statement submitted' bybTr. Cohen follbavs:] I P P An be cl za to off ea ri th ti, ex us s ai St'- rt,e se al pr M co Un
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; singled ht to be j Govern- p and to, ~out suffi ~ to slow . e United 1-y physi- t'o study- be left in ~es bef'ore ~ along the hought I d to say,, ! ,of law as~j, hot thinl: ReSearoh Park'„ Rou1e206 P rimce2on, New.Jersey ,08540 (609) 921 -3333' 69 STATEMENT OF REUBEN COHEN',, PR.ESIDENT, RESPONSE ANALYSIS. CORPORATION, PRINCETON, NEW JERSEY My name is Reuben Cohen. I am President of Response Analysis Corporati!on, a survey research organi''zatiion in Princeton, New Jersey. We conduct surveys of the opinions, attitudes, and behavior of the American public on a w'ide variety of topics. Our clients include companies in privat'e industry, academic organii- zations, and the Federal government. We were asked'by members of the U. S. tobacco industry to'conduct a survey of the annoyances and irritations that are part of the everyday life of American aduRts. Interestingly, the only earlier large-scalie study of this type that we know'about was car- ried out in the 1920's. Thus, one of the purposes was to update the earlier survey by reporting on current annoyances and irriita- tions. Naturally, a specific interest of our clients was in the extent' to which tobacco smoke came up when we asked people to tell us about the kinds of things that bother, irritate, or annoy them. Briefly, our procedure was to select an area probability sample of adults who live in'metropolitan areas of the Unit'ed States. The sampl'ing procedure we used'is the most up-to-date method available -- the households and people we talked to were selected on a random basis. It is basically the procedure used by all leadiing survey research organizations to provide accurate, projectable results to the total population of interest (for ex- ample, it is the procedure used'by the Bureau of the Census in conducting surveys to determi'ne the extent of unemployment in the United States).
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70 In our survey, we interviiewed 799 people in 49 different metropol!itan areas of the United'States. Interviews were conducted in July and August of 1977. We included cigarette smokers as well as nonsmokers, and the results have been analyzed separately for the two groups as well as for the total sample. There are a number of ways of measuring attitudes and no one survey wi1l provide a totali picture of a complex set of issues. Two broad approaches are in conmon use in our fielid'. One is a recognition method; the other iis a recall method. The recognitiom method presents a list of issues to respondents to elilcit feelings and attitudes about those iissues. Because the recognition method reminds people of topics they might not otherwise have thought of during the interview'it often produces higher numbers of inent'ions on . topics covered in the interview than methods which rely onirespon- dents to recalli specific events or incidents. When the recognition method is used, the results are highly dependent on the wording,of specific questions and may be poor estimates of the t'ruliy annoying aspects of modern life. The method we used is basically a recall approachi, but with a number of questions and probes to elicit a wide range of responses. This approach is appropriate to determining salience: How top-of- mind is a set of issues? How prominent are they in the consciousness of the public? Specifically, we asked peopl'e alnumber of open-end questions about their personallexperiences; our purpose was neither to lead them towardinor away from any particular topic, but rather intended to draw out as wide a collection of annoyances and irritations as we could. rLS .rGh al-no. "cst tion, 'he cus anno r,the e:on of t
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71 For example, one of the several questions we asked was: Most people have some things that annoy them, perhaps things they might see or hear other people doing, or other things they might see, hear, feell, or smell. What' about yesterdby--what specific things happened to annoy you yesterday? The questions and probes did suggest that we were interestedlin events that might have occurred in a variety of different types of places, events caused by other people, or affecting the senses of sight, hearing an&smell or feelings. The aim in the survey was to obtain as complete a liistimg of annoyances as possible within a survey interview procedure. Our sample of adults mentioned a wide range of topics. Almost everyone mentioned at least one annoying or irritating item. Most persons mentioned several: the average number of items men- tioned was five. The listing of annoyances is quite extensive. Those at the top in terms of freqNency of mention include annoyances of varii- Ous types related to manners or behavior of "other"'people, and annoyances relatedito automobiles, trucks, drivers, and traffic. Other examples of annoyances ranking,near the high end were those relbted to household and family matters; political, social, and~ economic issues; and annoyances related to employment or school. It might be of interest to the Conenittee to mention some of the responses as they were recorded verbatim: 3
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72 "People who~a.re late." "People who are rude." "Parents shouting at' their children in public places." "Immodesty and bad language that people use in public." "Loud voices, people arguing." "When someone slurps coffee." "My car would not start."' "Rude drivers; drivers who won't yield'the road'." "Heavy traffic."' "Highway noise." "Kids fighting." "Messy house." ..dirty house and'a messy kitchen." "The smell of garbage annoys me." "Violence, crime; a big problem that annoys me." "We have been burglarized three times in one year." "Inflationary prices bother me sometimes." "Government prying into each one's business too mueh:"' "I am extremely annoyed by inefficient clerks." "Garbage collection spills out of trucks and stays on the ground." "The trash in the streets and on the sidewalks." "The smog and air pollution some days really, irritates my eyes."' "Odor fromisewer nearby."' "hoise„ traffic and machinery, lawn mowers, loud cars, andiother loud noise."' "Barking dogs in the neighborhood." "Dogs getting into garbage." :J } °±l r relate- to smol groupir i rriltai annoyar ty man) by the annoyar 1!ated t sllightll as an,a not men usually report~e only 1. in the smaking of even
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73 5 `d1 cF llu Of specific interest t'o:this Commiittee are the annoyances related to smokers and tobacco smoke. Some of the annoyances related to smoke and smoking as recorded verbati'm are: "It irritates me that people who smoke drop their ashes alil over." "Cigarette smoke being blown in my face." "Smoking annoys me -- anyone who smokes in public."' The number of mentions of smokers or smoke places this grouping as number 12 among,l6 groupings of annoyances and irritations. The total sample made over 4,000 mentions of various annoyances. A specific annoyance might, of course, be mentioned by many persons or by only a few. Of the total annoyances mentioned by the entire sample, only 2 percent related to smoking!. Of the totall annoyances mentioned'by the nonsmokers in the sample, 3 percent re- lated~ to smoking!. If one examines nonsmokers as a group~, about one in seven -- slightly less than 14 percent -- ment'i6ned smoking or tobacco smoke as an annoyance at some point during the interview; 86 percent did not mention smoking at all. When a smoking-related annoyance was reported, it was usually mentioned'lat'e in the interview and by a person who had already reported: three or more other annoyances. For the sample as a whole, only 1.1 percent of the annoyances mentioned first, second', or third ih the interview were related to smoking. Thus, we can concllud'e that smoking-;-elat'ed annoyances were generally not uppermost in the minds of even those people who did! menti'on such an annoyance in our survey.
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74 I understand'that high ratings for smoking-related annoyances have been reported by other surveys. As Lmentioned earlier, these results would~ be difficult to evaluate without knowing the specifiic procedures and questions. Response levels can be affected by the details of question wording or int'roductory material. Our data clearly showthat in the group we interviewed, which was a representative sample, smoking annoyances were mentioned infrequently compared to many other types of annoyances. Smoking annoyances were 2 percent of the total reported, and were twelfth among the annoyance groupings. Thank you. I am pleased to answer any questions. Mr. Jc a very in ran out t hour is 1 subcomir for a ree statemen Ifihile it does sE. ~riith the adt ersee Idonot alone in guished other eoI liave no nlode(aI am haveJus 1ociallyto teach ~upport „uiltfee al-ainst.t There subj ect.. needed k pressedL tutes un, consensu lead us tc I have tmrnl! Corr ('hica~o publie p' ~~. At tI Thomas rause of entered't [The t ?24.] And s inittee, Al[11'hei [Tltre. , tional m: IloN. HoF rhe Yobd, 1S'ashingtI)EAR B Nvith othe concernin Iamte ]ect on o:
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ices d 75 Mr. JONES of North Carolina. Mr. Cohen, thank you very much for a very interesting survey. Thebells have tolled again, and perhaps we ran out at just about even time. I have a brief comment or tv-o: The hour is lat.e and I want to thank all of you for your assist'ance to the snbcommitteetoday.Without objeetion t'herecord will be kept open for a reasonable time for the receipt of any additionall views or sta.tements. While I know each~ of us will want to studyy this record carefully, it does seem obvious to me that perhaps we have struck a balance here u:t'hthemany speculative claims wshaveall heard! regarding asserte& acit-etse effects of tobacco smoke on people who do not smoke tobacco: I donot believethat t,hese eminent experts we havehe.ard t'arlay are alone in their analyses. Dr:Arthur. UUpton, for example, thedistin- L,~uished director of the National Cancer Institute, recently told an- rltliercommiitteeof theHouee ofRepresent!atives, and I quote, "We, . h,tive no evidence, to my knowl2dge; linking exposuret'hrough this nlode (atmospheric tobacco smoke) to cancer and heart disease." I aini begoinning tounderstand, that theolde attacks on smoking, ]tave just shifted to a new ground and the idea is to make smoking ~-ocially unaeceptable. There apparently has been a concerted effort,to teachi nonsmokers that their health is in dangelr;then to use theiir ,Nnpport inenact'img restrictions on smoking-and even eultivating, a~uilt feeling, among the smokers themselves so they won't speak out a:,Minst these measures. I'here are going to continue to be differences of opinion on, this slibject. I hopewhat we have done today will provide an obviously needed better balance of public awareness as these opinions are eg- 1?rnssed. It strikes me that a good deal of what wehaveheard consti- tnt~es unassailablescientific facts and if we are ever going to have a ('ciasensus on this matter, it will be scientific facts, not emotions, that lcarl'us to it. I]iav.e learned that following a hearing byt'he,Environmental: Con~- t i'f11 Committee, andl after a 11y2-hour debate on the floor by t'he'fuld tIlica,-_o City Council, a proposed ordinance to restrict smoking in llublic placesa-nd places of employment was rejected by a vote of 42 to T• At t-hat hearing, statements were presented byDoctorsHirarn Thonlas Langston, Domingo, M. Aviado, and Lee R. Nylander. Be- rallseof thegermaneness of these statements toourhearings; I have hnthred them into the record. f The abovereferred to stat'emernt's maybe f!ound on pp; 158,,185' and '''z4.] -laid' so if there is no further business to come before the subcom- mittee, we are adjourned. F«-bereupony at 1:05 p.m., the hearing was adjourned.] IIThv correspondence, referred! to by Mr. Jones on p. 2, and addi- tiiInMl nrateri'al submitted to the,subcotnmittee: follow :] llot Auaus~ 1S 1978. T.h~ IIbRAQE KGH.TEGAY„ Thha.cco institute, St"QBh{>I /JtQRi. D, (~i ~ 1i"la Hoa_.cE : As Chairman of the House Subcommittee on Tobacco, along "it11 nther_liembers of CongFess; I have becomeincreasinglcaware of charges. ry'ncerning claimed effects of tobacco smoke on nonsmokers: 1 ain tentatively makibgplans to conduct Subcommittee hearings on this sub- l~ct on, or about September 7, 1978. I thought! it mightl well, be that you have
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76 knowledge of some experts or researchers in this particular area who you would~, like to invite to appear before the Subcommittee. If the meeting definitely mate- ~ rialiees I will notify you in ample time. ~t Already I have taken the liberty of' contacting Dr. Edwin R. Fisher of th"" University of Pittsburgh and Dr. Walter M. Booker of Washington, D.C., who have indicated a willingness to appear. I will appreciate it if you think it wise ` to advise the Tobacco Associates, Inc. and the Tobacco Growers' Information`- Committee in order that they might,be thinking of any, contribution they might ~, ,' make to this hearing. I appreciate your interest in~ this matter ; and with warmest personal regards,., I am. Sincerely,, wALTEB B. JO1tiE6,. 'n Member of Congress. Id TM .,-5 K~3'.'. Dra TOL : he Wall ~ ~. Was De a 197 con c1a a s kDOt ^'o eLc bee cor _ec si1cS occ 'ha ic.^.c •J^i Mak . I a _nd Ver w_t _cr cf Als Bil and'. tic The wit aoc the con Wit 34-
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77 would 1'mate+ of the ., who t wise nation ,might I gards, I r I Y ieaa. THE TOBACCO INSTITUTE t"6'.K.STtiEET. \ORTH`.cEST,w:qSHiVCtt7N, D.Q. znpos. :0?,<as7.aaooGUR TOLL FREE :VL?adEA IS, 800ta14•8876 T,he Honorable Walter B. Jones U.. S. House of ftepresentatives Washington, D. C. 20515 HORACE R.. KORtiECAY Prevd2nt 202.'45%-1fi:i0 August 3,, 1978 Dear Walter: ti )3 14 I A :3 7 -his is to acknowledge receipt of your letter of August 1, 1978, and to let you know I' am deliighted that you plan to conduct Subcommittee hearings an the charges concerning claimed effects of tobacco smoke on nonsmokers. This is a subject which has received considerable attention recently, both within and without government. To diate most of this attention has taken the form of one- sided unscientific charges that smoking in public places has beenishown to cause disease in nonsmokers. This is not correct. unfortunately Secretary Cal!i`ano's statements regardinq,this subject have not provided the type of dispas- sionate scientific analysis we would expec: from an -^dividual occupying his position. It is therefore extremely i°portant that information, concerning the true state of scientific knowledce in this area be obtained and made available =c decision makers in all' levels of government. The hearings which you are planning to conduct could be invaluable in making that type of information available. i am, v,eryp,leased to hear that Dr. Fisiieran1 Dr. Booker havsindicated a willing,ness to appear before your Scbcor=i,t*_ee. Very shortly I will be happy to advise you of other expert witnesses whom I am sure will be able to provide your Sub- committee with important information concernin.g the subject of your hearings. Also, I will be coord:na*_ing with Joe Williams, Tobacco Associates, Billy Yeargin of the Tobacco Growers Information Comnit_tee, Inc., and Frank B. Snodgrass, Burley & Dark Leaf Tobacco Export F+ssocia- tion,,Inc., to insure their attention to the heari'ng,, and your invitation to recommend witnesses is extended to~all concerned. The Tobacco Institute will be pleased to defer the costs of witnesses attendi'.zg your Subcommittee hearing if you deem this appropriate, but I am sure the witnesses would most appreciate the invitation be extendediby you as the Chaisnan,of the 5ub- comnittee. With all good wishes, I am Sincerely yours„ Horace P. Kornegay President The Tobacco Institu.te,. Inc. E 34~-[p{ p~-78 - 5~. ®
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SHRS'T'SIEDE HOSPITRL ~~allrIt~y cE •aE:.ve ~E . o,+ae. A:e .c. s:;e . X~&p{}(~(3fX. 412=622-2315 EDwi." a. riSnEA tit ~ oa-o.. July 18, 1978 WaLter B. Jones, Chairman, Tobacco Information Committee Congress of the United States House of Representatives Washington, D.C', 20515 Dear Representative Jones: I am in receipt of your Letter of July 14, 1978 relating to your planned seminar regarding the controversy about passive smoking,scheduled for September 7, 1978. I shall be most happy to attend'this meeting,and sincerely hope that it may provide information permitting for a more rational perspective concerning this problem than the public has been led to believe. Ii wouldibe grateful if you couldlprovide me with informationiconcerning the site of this meeting as well as its expected durationi. In response to your inquiry concerning other individuals who might provide some scientific input into the discussions, I have taken the liberty of providing you with the following: (1) Dr. Suzanne B. Knoebel Krannert Institute of Cardiology. 1001 West 10th Street Indianapolis, Indiana 462-02' (2) Dr. Kenneth Moser University Hospital of San Diego 225 West Dickinson Street San Diego, California 92103' (3) Dr. John Salvaggio Clinical, Immunology Sectioni School of Medicine Tulane University 1700 Perdido Street New Orleans, Louisiana 70112 Again, let me thank you for your invitation and the opportunity to participate in this very important meeting. r ~_ncere.ly yours >> • ~ EDWINi K. FZ: SHER., M.D. Director of' Laboratories Professor of Pathology. Uhiversity of Pittsburgti
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79 I il! I ~~illilL~~ . OR. INALTER'M. BOOKER 6 ASSOCIATES JOECAL CONSULTANT SERVECES . . . - . . . . Syccirr)ties. ,/ Ilae CONNEGiICUT AV2NUE: N W.' Herrody~amicsof G-~~g~. / 5u'1E eoc To.~,:1y.c• WASMINGr~N, D C2C6]b Bia.em'ca' St I 'EIEFNCNE 1]03/ 196-0C90 Honorable Wal ter 8:..JonesHouse of Representatives Washington, D: C. 20S15 DearCong.ressman Jones: July 26, 1978' Gra Ci Pro .. Med~atl leqa~" Azister., Iihavereceived your letter.of July14andgladiy accept' yourinvitation to.participate in a seminar scheduled for September 7, 1998; in Washington.. It is.gaatifying.to khoww that some people aretaking theop,portunity to study an, issue that has.b'een charac- terized1by so.much rhe.toricc andmisinformation. 91 Dr:..Theodor. D. SterlingDirector, Computer Seience.Program, Simon Fraser, UniversityBurnaby. 2„ British..Co:lumbia Canada 2: Dr..Norman W. Heimstra -- Dr.,Heimstra is-experimental psychologisn who~specializes in the analysisofhuman behavior. His Human FactorsLabo.ratflryhasstudiedvarious. aspectsof.thesmoking issue including.thebehavioraY comse- qpences of smoking,d4privation.. Hee canben contaoted.atUniversity address: Dr:.Norman W. Heimstra Deparsment of Psychology. Dniversity of SouthDakota Vermi~llion, South Dakota 57069' In accordan~cewith,your request for thenameso:f'otherqualified1expertsthar.are.know.ledgeab'lein thepublic smoking.area„ Iisuggest the following: .. .. 11. Dr. TheodorD. Sterling.--Dr...Sterlingisan act t scientist.in the area of environmental and occupational health. -In particular,.hehas written~on the subject of z ironmentalexposures i-nciosed "living" " spaces.. address is as follows: 3. Reuben Cohen- Mr. Cohen is a highly regarded specialist in the fi.eldlof opinion and attitude researchL Most recently, hisorganization has.conducted a large scale survey.of the American pub'lic.todiscoverwhat annoyancesandirritationsare.e~neountered in every'.day.life. His address is as.folM1ows.: Mi- ReubenCohen, President Response AnalysisCorporation, R'esearch! , Park, Route206. Princeton, New Jersey 08540' ~ You.a e probatilyay e tha.t Minnesorahasadopted a laww restrictingg smokingin certain public p.laces, It might be approp,riateto invite some- one to your seminar who hasknowledgeof the Minncsotaexperienc.. I am not pre_sently in a positibn to.suggest any particular person but I:may,beableto~make such a suggestion in~thlefuture. Thank you for your invitation and I look.forwardto.attending the seminar. Very trulyy yours, Wa.lter M. ~ookler;,Ph.D., H.A.C.C. Presidbnt I
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80 STATEMENT HON..JOHNIB, BRECKINR[DCETOBACCO:SUBCOMMITTiEE HEARINGS, EFFECT OF'SMOK'INGONNON;-SMOKERS SEP['EMBER.7„ 1978. Mr..Chairrnan,.Miambers.ofthe Subcommittee and guests. I am privilegedlto be here today'to receive the t'estimony from what appears to be a most distinguished'and knowledgeable group of witnesses reggrding the effects of smoking on non-smokers. The Chairman and Subcommittee are commended in~li~ght.ofr~ecent governmental and. Congressional efforts to present! a one«sided! approach to this complicated and controversial topic. Mr. Chairman, I wiLU be the first to admit that seribus.questions continue to persist about tobacco. I wilR also be the first.to say that my, state - Kent'~ucky - has made the proper and~logical response to finding answers to the questions about this crop which is so very important to Kentucky's economic well being. Caown in all of Kentucky's 120 counties, tobacco.d.iseetly effects more than 164,000. Kent'~ucky farm families and! 13,900.fartoryworkers;.allnost 25 percentt of Kentuckians, sxme800,000 p,eople,.are involved in some aspect of the tobacco industry.Kentuekyis the second largest tobacco growing and the third largest tobacco manufacturing state in America. Tobaecoy which has brought in $566 million last year, is Kentbcky'slargest cash crop. Uniquely, the citizens of our state have proposed a special tax on those who purchase eigarettestherein order to . support the massive scientific research on smoking and health now underwayatr the Universityy ofKentucky's.Tobacco~ Research Institute. 'lhrough research we work to identify alleged'in3urious substances found to exist in tobacco and to remove them, th'ereby to retain both the economic stability of the tobacco farmer and the health of the smoking public. Since the Tobacco Re.seareh.Institute''s creation in,1972,.more than$3.7milli~on has been directedlinto.unprecedented research and study of tobacco in addition to the University's ongoinggenetie researeh.and development which had then been underway for over a generation. Current research consequently focuses on.the relationship between tobacco srnakec.anpounds and any observed "abnormalities in the production of cells". Other projects examinetheeffectsofnicot.ime,,long a sus- pected~culprit, on the cardiovascular and nervous systems, and the relation- ship between aldehydes.(formed from tobacco plant sugars during curing)) and airway diseases - bronchitis and emphysema': as de, ni~ is coi of hai ch, . gr, Am, ce: inn th in wh: h o:. vol euj, de buw let imi, to of in am: tai quc
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81 ,ng ire ;c. ~ It ,ng .on ,tion- I find it ironic thatiwe have to contemplate a renewaL of government assaults.on tobacco at the veryt,ime when the marketplace itself issorapidlyd'ealing,with the problem that smoking adversaries talk so much.about.. Tarand'r nicotineyiel.d'shave.been cut in half in.recent years. Theeigarette industry is involved int~he most vigorous and expensive competition in it'~s historyy to convert smokerstM th'elow-tarbrands. We are seeing a clessic illustrati'on ofl tlie.value of fireedom,of choice -- the free choice of smokers on the one hand, to smoke the cigarettes that their, critics say are safer, andlthe free choieeof the manufacturers on.the otherhand~to respond competitively to that growing market. But, more importantly, we must struggle to receive andldisseminate to the American people the facts on the effects of smoking;. I do not suggest that ex- cessive smoking is harmless, but.wetodayhave an obligation,to present health information fully and objectively to~the American people. I am confident that the public, if given the fact'~s in a balanced and truthful manner, williact wisely in protecting its own health. I need not review for tbissubconmittee the economics.ofl th'etobaccoindustrywhich eneompasses.an appreciable portion of this country'sagrieultural 1.iveUi- hoods. Across the nationy over 700,000 production workers and farmers are in- volved in.the tobacco industry..: The 625.,0000 farmers rely heavily on thepr:icesupport program that was instituted 43 years ago. Tobacco price support destruction would bankrupt hundreds of thousands of farmers,.landowners, - businessmen, financial institutions and others. The UnitediStates, as we know, is the leading producer of tobacco and the leading exporter as well. With the difference betweentobaceoexports.and imports, the.tobacco industryprovided~anet eontmibution of over $1.1 bililion~ toour 1976 balance of payments. This economic booster is another indication of tobacco's impact in the United States - not to mention th'e greatest impact in the form of t~axrevenues.. Federal, state and lbcal excise.t~axes on tobaecoo amounted to $6,0 billion in 1977. Oneacre of tobaeco:generates $12,177 . in taxes that is distributedd to all levels of government. Hbw we can best deaTwith the.problems of smoking and health is aa serious question Ih'ope this hearing,wilil address today,.. Thank you.
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82 Statementt ofDr,., Russelli L. Stedman, Biochemicali Consult.ant, Temple University I am Dr.. Russell L. Stedman. I hold Bachelor of Science, Master of Science and Doctor oi Science degrees with majors in chemistry and microbiology. From 1956 to I'970 I headed;research on tobacco.and tobacco smoke at the EasternRe.gional Research Center of the U.S. Department of Agriculture at Philadelphia. During part of this time,,I aliso served on the Interagency Task Force on Smoking and HeaLth and assisted in the preparation of the annual reports of the Public Health Service on.Smoking and: Healith. Subsequent to 1964, my tobacco research group at the Eastern Center (which was the largest chemical research effort among Federal laboratories)) worked exclusively in the area of tobacco and1health. I became Assistant Director of the Center in1970~and:retired in119.72... From 1964-1902, a total of 42 technical papers were published by the group. My group at the Eastern Research Center spent'several years studying the brown pigments that are in tobacco leaf and in tobacco smoke condensate. In general we found that both leaf and smoke condensate pigments were highly complex mixtures that show some superficiall similarities but are,.infact,quitedifferent chemically. The lieaf pigments are apparently related to brown pigments found ihn a wide variety of plants, including potatoes and;other vegetables. Accordingly, they are not specific for tobacco. Since my retirement, I have remained professionally active. At present, I am,a biochemical consultant to Templ'e.Universityand \ a consultant to the tobacco industry in the same research areas in which I was involved at the Eastern Research Center.
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M rsicy rom pars Wco lcallyL q in !s. -2- During the past two years Dr. Carl G. Becker and hiss colleagues at CornelL University Medicali College and Center in New York City, have published articles in the scientific literature about a certain material which they claim to have extracted from tobacco lieaf, as well as fromicigarette smoke and cigarette smoke condensate. According,to these workers, this brown pigmented material, which they call!"'tobacco glycoprotein," causes alilergic reactions in humans and'might well be responsible for pulmonary and cardiovascular diseases statistically associated with smoking. Dr. Becker and his coworkers have also isolated a similar material! from eggpl!ants,, green peppers, tomatoes and potatoes.. Based upom my own work at the Eastern Research Center and my review of the scientific literature, I was unconvinced that Dr. Becker and his colileagues had'demonstrated the presence of a human allergen in either tobacco smoke or tobacco smoke condensate. My reasons can briefly be stated as follows: -- Dr. Becker reported the prcduction of allergic skin reactions in human volunteers with "'tobacco glycoprotein" but does not indicate whether the material used in these studies was from tobacco leaf or tobacco smoke condensate. Because the pig- mented materials allegedly isolated from tobacco smoke condensate and tobacco smoke had certain superficial similarities to the leaf pigments, he assumed that the materials were identical. However,, as noted above, the tobacco smoke condensate pigments are quite different chemically from the leaf pigments. \ V
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84 - 3- mLdegel electrophoresis,,which introduced an extraneous contaminant -- Dr. Becker characterized the extracted materiali as a "glycoprotein," which is by definition a combination of a sugar and a protein linked together in a large molecule. He basedihis characterization upon a few simple tests, as welil as various reports in the scientific literature including two by me and my col'leagues at the Eastern Research Center. However, neither the tests that Dr. Becker performedd mrthe sci~entific literature which he cites, specifically the papers by my group, establish that the extracted material is a gliycoprotein. -- Dr. Becker reported that "tobacco glycoprotein" fromm leaf and from cigarette smoke condensate contained rutin or a r•itin-1ik.e substance with certain biological characteristics. However, Dr. Becker presented no evidence that "tobacco glycopro- tein" actually contained rutin; he j;ust assumed that it did;. To the contrary of this assumption, our past work at the Eastern Research Center showed that rutin is a component in the brown pig- ment of tobacco leaf but not in the pigment from cigarette smoke condensate. This fact was published in scientific literature in 11966. . ( R. L. Stedman.et a1..,. High Molecular Weight Pigment in Cigarette Smoke, Chemistry and Industry: 1560-1562, 11966.) During the past several months I have been involved in research aimed at repeating Dr. Becker's work in order to see if, following his published procedures, a material with the claimed biological characteristics could be extracted from either tobacco leaf or tobacco smoke condensate. As a result of this research I must conclude that' Dr. Becker's methods pf isolation were not carefulQy selectedL Indeed, he used onelmethod;called polyacryla- intc Accc Be ck and sepa ;Ji e beer .:hic at t cene
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85 _q_ into the brown pigmented materials later used in biological tests. Accordingly,, the material called "tobacco glyccprotein" by Dr. Becker and his coworkers appears to be a mixture of tobacco material and substantial extraneous chemical's formed as side products in the separation step called polyacrylamide gel electrophoresis. t4oreover,, the fact that this technique introduces extraneous contaminants has bee.ndocumented in the scientificli~terature.. See attached article which~ appearediin Science in 1971. Unfortunately„ we are not ab1!e at this time to characterize precisely the chemical nature or even generally the biological nature of these contaminants. In~conclusion, I am not convinced that Dr. Becker and his colleagues have extracted a human allergen fromieither tobacco:smoke or tobacco smbke condensate. Further, it appears that the separation procedure that they usediintroduced a substantial artifact. a
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86 aep"r„zd Iro,m 30 Apa11197.1; volume 172, pp. d60-a51 FoEvacryiamide Gei E''eetrophorPsis A...Clirambach and D. Rodbard Fractionation of proteins, niucdeicaeids, and other chargcd ma¢romole- tulhs has gencrallyrequiredlsucceuive tue of severa] fractionation steps,, one scnsitivc primarily to molecuiar sire(sueh,argcl fillratVnm) and arvolhceb'ased mairtly'on molccu1ar ned eharge (suoh as free clcctropliuresis, ion exchange chromoro-gmph'y); . Zome . elec9rophonesis in polyaerylamid'c gel (1;,2); designatedl as polracryl'amidee gel' electrophoresis(PAGE), simultaneously. exploitss dPRer-eacesin molecular size and ehargefor purposcsof fractionation. Range.r o/,apVhcability: The sy nth'ct ic polymcr, polyacrlamide, can be madce to provide an eflcetive mediam pore radius.of'0-5 to 3'nm (3)~bytlu siinplce deviec of ad7wrslingg the total acrylansidc conccntration, dcsigoatcd. (S). %T (3' to 30 0w/v) (.r, 6), and the coocea- tration oCcross-linAing arent, designated (<).4'4C (1 to 25°0 of'.lotalimonomer). ' in ~ th'e poly ~mcrizati'ou reaction (Fg. 1). hrger poresius can be p,roduecd when the poly.;ter isstabi6ized by' agarox. (7-9). The pore siz`-s ean busclectcd for optimal -oluoion between anyy twospecics (!0). The widc rango of applica- biltityo( PAGE is iDlustrated by' the fractionatio.n of bligonuclcotidcs (M:B': < 1000) (5) and high-rrnokoulxr-weigh't RNA.(M.1v.> 10^) (6;.5; 9). Onc can', also optimize "charge separation" byoperarietgat any.pH betwecn3 and 11 tn provide the ma.aimal diffcrance be- 7TaanrMm a~rt .cnbrlnsaneaton tn Ws 1<s- Prod~et n.Rnearth aranan of n,e NuionY Iva Ch,iJ Neanl,'..nE Ilviea.,, il..efopment. asae. Ms.runa aa~s. (;Lpyripltt' 1`J7J Gythr AmrricrsnAvocih~ion for tlsrAdunecrmrnrofScience I'r+G t::crc 1Y1 • (75),. tracti Io.~JJ uf i Jo nnce Es ccper {~ul7r is or a tonn The facc and : thc g ~and nri c lae g ~mh ro. of v. th ol r'11 onwi mp:. C0U [iY<c su.:h ruhJ~ char :G)f Pl:ci Cucc (F /.nu (:41i d-C
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87 otol lacrylamide A (d) ~ %7 (3 od'the coneen- gent, dcsignated. Ictal monotner) action (Fig, 1)- pnoduced whan ed'I by agattne an ticselcctcd etw'een any'y two mge of applica- strated by, the ;Icoti'dcs (h1:W, ioleeullr-weight S; 9). One Can separation" byy wecn 3 and 111 ~ dif9erence bo- nh*on M us< Ae- f e Nulonal ro- mm~ ,De.etw~4 L.cen ~i,c ~~xtci~oiycs of~.niulcculdx(V/). PAGG can be earrfcJ'out at 0"C :~ wc11 I a.al hii;'hcr tcmptratures,and in t::crcfoeeapplkablr toensymrts (1?- ).q and other thermolabilr moln:a:ks (Y5),.PAGE can bo uscJ for.analyti¢al fractlonatlon in or below microgram bads orr for prcparativc' ftuctionation of' loadv' in thc mililigram and gramr.lnre: E.rrerimenle).Smpf:Eily'• The baacexpcnmcnEal sctup (16) (center of Fig : ]1 ie vmple. The gcl isformed by pnlynncrization of acryl5mide in a tubc or eslab mold. The gcl tubeis.posi- uuned bctwcen two SuBer ehambers. The sample is applied 10 the gel. sur" fa¢e in a 10. l0 50^osuerose so).ution,. anJ',,,n electrical field is applkd acroa. 1Lc.gcl. Each compomcnt migralcs as a band whti characlcristio elcerrophorauc :raGonr.ilc Jcpcnd.mp on its sizc and nce charge{Eq..21 (10. 11~ /7).,Fisatlon and staininr, or slicing . andlassa-v,.of i)mpcl isubscqucnt lo clcclropAornis re- vral. thccharaclcri.itrc bandIposilions, f'r'uriiiryy of pulyurryPdmfde. ge6. Pore sleo variabillry. achieved 'ayuce of vsriahlc. conccntratinns of reagrr.t<tha pnLymuriratinm r .-ion.(Fig. I): n"~nly rc. p onsiblc, ponsiblc fur lh'ce vcrsatiluy of l'ACiT. Furthcr vcrsatilityy can heoht, incd. (i) Gcl hufRrscontaining, urca (13). nonfonucc detergent (for es- ampl.c: Triton-X-100). (19): (ormamid! C'ul. ph'envl(?/),. sworusc (/6), or, Vjnrol (P?).com he a.cd. (ii).Polymor.s-hias agarose(7-9) or pmlyvihyl)+yr- roWo.ne.(23)• or vinyl monomers with~ chs,cd (24) or other hydroph'ilic (25; ?,).fL.nctin.nal proups can bcintroduoed ,mo the polymcrizatVOr• rcacaiom. (iii) F.I;ara.pfiorcaisi cann be uscd tointro- d•-ce iu:nie delergents (27); slab'ilizing aFcl',s,, cofactnrs, (2R),, ohclating . agents(Ai. li(•ands(/5), or redu¢ina agents (:97 inlothe gcl. .uch v rn:0Gic+a.c of PAGE imposcsresificriom with rcgard to apparatus, d-~gn zndcon;i ruction.. Adeqwmee wall'ad~<rcnce under wldely dL^,crin, anndi- I '•'nsia ohdc obl.dnedlin Pyrcx.tubcx or ' s. Ever: scllh gVass, wnlls... gefs of I"~'•t mounmer eoncentrmions(II tn 3 ~.~ ~/a nttd I staS'ill¢alion by. hydruslati¢ w;ill. roatine "ith li"~-r.^po''S;,crylAmidc (30) , onmechanf' cxf 'up;xom. Inylon mcsh or dia;csis. mcnnbran~n9(31). qnaliraricc roquanriian~< itecamcof itshigh resclving, applieabiluy to the entircmo- sccvl,ra-cight runge,. scnsillvity, versa- f-•7'. s.m'llcity, self'-suficiency, and KOnOmy: I'AGE hxs foumd widcs,^,rcad Cvz-c;,M!a-U It C-o c-0 NHi NN' I '~ I ,~^CK --o Clla-CN-CY•i; CN-CNj-t.li_ I f-o f-o 1I 1 NMa NMj NN C-O ', c-OCI '-O ~ [Nj- CN~ CNa--r - - iN~ fC•H}ON)i-CNiON t-~oa~-f', fsaC C-O, + fCHSIa-N-GN-Crra- f( fyC C /NN M •a> o F-F-: 1. Th polf"neri~auon re,cu firylinnid- The s:ruat resof acryl mide, N,N'-<thly:e h ac )linude and nf ....... ,at- ecgmer~ of c oss-linked'.p lyacryliLnide are sh-n ~/niu~cors, dnihnated hy i,shown ~.,.rc pcnulfaie. rtboflf.in,, and N',N,N'N'- tcrramethylcthy!enediirnine. Ligh~, i. designaied as 1- applicationsinccitsn introduation10 ycxrsago (1, 2)~A (sdd account of its app,licvtlonsand' instrunrcntationi isgiven byy two recent, monographs. (.j2) nnd b*ra, pericdicalfiy,updatcd bi~blinr- raphy (3.t). However, most'of its ap; pli¢s'tions havc u•cd onl~yy qqiali;tativr pattern inspcaionn for in~tcrprctiHion of rc.udts and h:.•r nottalen advsnlare ofthe quantilat-iPc physica4chcmicd nmluree of PAGE, which is thercforc cmphasizcd in thisrcvicw: Quantitativc PAGE is bascdd on (1) dcvrlopm¢nt.of methods toachitsre a high degree of pore sizc rcp,roducibility;. (ii)) dcvclopt ment of the ph)'xical-chcmical theory ofthe movemcnt.of molccules through gels„leading to the quantltntivc and sta tictical analysis of PAGEdata bycom- putorizedl mclhodi; (iii)i developnneat~ ofan ecacl theoryan&computer, pro-gram. for the generation of'multiphasic(disonti.nuous).buRer systems.oper:slive at any. pH. at 0^or 25'C. The three adyancesan~d the develop,ment'.ur, pre- parative PAGE allow forrnulation ofagencnl strato, gy applicable to the frac- tiomolinn, recolution• pF,ysicalKhcmiql charactcrizaiium, and isulatimn of macro- molcculcs. The PolweryLimidePisre ronNarun of areproduolhJc p,orer The polymerization reaction. (flig:. 1) that forms the gel . has to be earricd oul dc nosn priorto cach fractionation, sinec Ore sur(aec and'swctling proper, ties afllhe getland bulfer dlsconGnuiuies do no6 permfrsloragc„Sunce thirc.intro- dswes an elementt of irreproducibihty' imtoPAGE: it is.impcntlvc lo control polymerization conditiora to enab'~Ie onee to.intcrpretthe dsta quantitativefy: Thiscontroli is achieved in~ Bveways: (i). Rearcnts arc purifed.. Aerylamide and N:N-mcthylcnebis:mrryianild ¢-cthylcnebis:mrryianild¢ (8is) (Fig, 1)'.are freed of polcmcna.nd eon- tami-ting ions.bys reerystolldzation (ll: 34,. 35). Ethylcncdincrylatc (36) and N, N. N", .V'-l etra mcsh y1c t h ylQned iami ne' (TE\IED), (Fig, 1)arc rcdisti6lcd r, vaeuo..BuRers aree purified ifncces• sary: (iP) Optimal polymcrizatimeseata- lysts(miaiatort) andd eonecntratioos aroselccted for each pH end buHer: Cata- Iystn(potassium pcrsulfate (I1~ . 16), riboflavin (16,.37; 38), TEDtED! (l6), H_O. - Fr=* (.?5),, persulfate-bisulfite (40), and others (26, 4l)) are used in, sucK eoncentrations as needed toachievr polymcrization within 5 to 15 mimutes (l1, 33) forgels 6mm in diam- clcr and toachicve 95Soor higin•r convcnio•n of monomer to, polymcr(IY). (iii). Pol'ymerization inhibiton are reduced andmaihtained at a constant levcG The mov: important po)ymcr- ization inhi.bhor is atmospSCri¢c oaygeo.. On.yg~en coneentntion, can be lowered' by regulated and timed~'deacralion ({1)'or saturation with aninert gu such as argon (42). Thiss becomc es- senaial. when operating at O'C and at aeid pH (Il). Appsratus materia4smayalso inhibirt (polyp,ropylene (4311• or en- hance (rubber (44)),polymariznlion. (ir). Temperaturc of polymeriulio,is kepteonstant. Thepolj•marizalion rate ist h'ighlytcmperature depcndenL C6n- stancy of . tempcrature within I°C cao
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88 mly (<'. u_ !creundhion. o!. c0icix t. n.!: dbsipanun slncc polym- cnztlio.i~ iscxothcrmio. Ltmitat.iur ul', gcl thielness. (5.to 14.mm):,sae ofthiin glasse•alls, imincrsiori o(Ithe gel tub'esor slab imo IiGuid (Pig. 2):. and faprd cool:vnt Iluw. (ron, a revcrvo!n ofadbquaic oapacuty arc raquired. The tcm- peraturc of polymerizatimn shoull be Ifiessmeasthe tempemturcof electro- p,lwresis locliminale lhermal contrx• sion or cxpalrsion of the gel. (v);Auniform ratc of the polqm r_dion rcac:tion nnaiutaincd. Polrymcri-t- should. be completed wiihin 5 to I S,mih- utcs, as,jud9•cd by:fhterface sh'arpening Silnce cuimpletion ir approached usymp- wsiaall):, a py:tctlcal proccdurcr., to. Ic:we the rcacGon mixture: undisturb'ed for, a co.nstant,. arhitrarty tiiinc, such a300 mirmtcs (60 mimules forr preparative5 slzc geis), ( IJ, 35).. Po!ymcrization . tnq'should be at Icaat 95So; 91 sa:a.can hc obtalhied. (11).. PuriGcation of the p,ol}pmer tocliml- natc calalyats. mono.mer, and~sidc produets is usumllyunnccessarY. \\'hemn nddCnee ineiaca:c: rcaction bet.vicen, mplc and -tnlyst. (?Y, 45)i or rrtsidl u.il nw.mmnwr, f4nl: pwrificulimnof thc ,-'ci: u^.~y 'icpoy.i.hl, . by prc•,lr_Iru- Ishuresfs(d; 9)) or tiyf s eapiot; of thc. Fcf. wl4h th~o,llcol.ac (?9; Yore size..S.:veral models have b'cen, postul,tcdi for thre gcornctryof the rwl):1cryhmidc gol purc. (l; 47. -J4):,ii'. .d med. in ahcu nuodcls tha:l all Ixmr zliavc Ilu'sa. ic simande shapcn A morcc ealis:ic and informauive approachi tofnrego. anyy preconceptionof gcl structurc b~a.nd comsidcration of gcls , andom mcsh. orksof fiA'orr("fOgvon thmory:-"(4l)I. lhc statistical.thcory of~ such a gclIstructurc hns becn~caacn- sively : develo„ed(10. 49-31) and pro- vidcsas uniificd approach to.gcl ctcctro- p)iu-isandlgci Gltration: "Pores" are nul unifonn in sizc; ruthcr, they are diitributed! accordirg to~ a. slightl): skcucdd n .n-Gau,sian d,stribulion,(10.' 49, SO). Thc dimcnsions of the poly nery Ilmidc pore andd gel fibcr hava becn c. ! . ac:+insr tha knownn dinensinns of macromolceules by meanxof gel filtrullon 1J,.3?).nnJ gcl clcccrophoresis (70)- Tno mcdian pure sizc;.R„r„ for anv.g¢liconcemtratlon can be estimated as thcrad.iusof a macrornoheculcfor which the partition coc0ieicnt' A-„ = 0.5(?, .5~; 5J), orlur which Ihu clcc- Bl1riEF 0 a5 umH wE9nnvE B'SrM~6' " P57HI5' T.ao T1S- ].40 T[S unoer ' L] I 8 Ej 6. CA; 7.40 TES- upow Ge~' ~\1\ C 7.12 U' 7.60 TE5' ~~~~- -- --- IGr~ fffk °"` ~ ~~~.,},~-7.1a C ct' r.zs C<C- ~ \ 2 'r-62 el" ~:2e Ct^ Le.w nonluure!icrc mohiSit; is 0.5 . tSmes ffis. `. ficee niobility(70).~ Mcdiao pore s•tin ~ X,;;,,, is inversely related to the.square.` roott of total gel concentration, %T ;(Fig.3)(3, 1Q 49, 52); Thce effective.! length of:get fbers,pcr unit volume, _' L, ic propmrfloaa6 to gcl conccnhaticns q76T, 20ranyconstant cross•limking,', %C (j), Properticsn of the gel can be. ; altered significantly', by edangiog %C. ' I-ow crnssdinkiog (I to. 5 Sa C). yields . "long . fiber geli,", in which the frac- y lional voltsmc available to amacro- mo!cculde thcorcticafly dcpcnds on m0- leeuldr surface area. A Aigh: percent eross-li'eking(15 to 25 %C or rrsorc) may resuH.in "shoat.fibcr gels," which theoretleadly can be e%pecUCd'to ap• proach . apore size which exdudes . macromoleculcs on the basis of moleo• . ular, vofume (J„ !0, 51): The effective lhia'..'ness of the hydrated polyacry6 amide gcliflber.r (Eq- I) alio,dependl on percent cross•lihkiii low (I to 4).. 1"rCresulLs inif+ber thickncssofabout, I nms, camparablc to Ih'ab of' cross- linked dCxiran i(3); high (15 to 25):'1'vCresolts in a~very Ihick'fiber (about:3' nm~), eomparubte to that of starch gels' (rccafculntion of'dAta from (S4)). with an opaq.uc gel, po.sslblyy duc to ~"bun•`. dlimg?(3) or ta ~ fiber brezkape at ~ the poi.ntr of~~ cross-linking. Estimates of Bbcr tldcknessob'tained by PAGE ard gcd OflraGon arcin rcavonahld aSrce- mcnb with -lrtes obtained by ind4pen- dcnt mcasurcment (551. Thc dimensions of n 2:bC pofyacryiamide gel areeorts. - parobla.to Ihoscof:a eross-lihkeddec- trmn gel of simillr polymer eonceo- tration (3; 52): . Pmc grrrairnrs. Soverall worken bave uscd porc gradients.(gcl conccntralion gradcnts), to provide a widuspeetrumof pore sizes in a single fractionatiom (56-58): An exact theory of the be- ha.ior of macromolcculcs on~ both lincarr and nonlinear gradiknts hasbcee dCvcloped. makimgi9.possi0le to predid the positbn a:nd'veloci:ty for any mb letular species as a function of time (59).(Fq_ 1), p 5 7-S p, 15. XTi Fig. ?. Szhem.aic rcn:ncnoailmn,ot appry;.renns for onalyilca6 PAGE. Polyacqlamrille Bels. of 5, 7.5, 10. anul f5`:: a e show.n..Rovinexnim alh.umin ii.fraciinma•.ed. Char.acteristic. e syown for. sys- pH values fu- ihe s, 'n~ili.;,l a opcr,,fi.c t9:1 bufferphues ar lem D!71i. S~.tek'.m; ncl::a ind,ui2d. hyth'.ccr-u-haichcd'-s aMovee the sepsna- tion gclifJtotographs. Upper and lower bnlfenin rr:cir respeclivereservoirs arem shown wilh . sLic . Coo1a u w th n 11- j+-ACII c lowe r onv/r t represeeted'h'yseripr.nd t.ied : rnn ofuwl t f~wiv :.ated by the . short.arro s., GISTI."15= ftis{n-hvdroxyelliyi)ilninutri,(hydAnxy~Te:hy~llm~ iatf,:.ne; TF.S- A'-nslhydrnTymcth~yf). m<th'yl-2-a:ntnornetnanesnl/amic. a¢i.J'. C.-1C- ucnJyhc ari,f; Cr = hyJr,xhdnrii aeid: :oT= :Icpncen0rallon. 1og,fnn:u:r}exp(LT.)1-bT. z- -8as u. v-6e,v.r+eap(bT.). a0 where ax iss distanee: :1 is Gnne; v is its% star.urucour celocity;;ua. is free mobidity, b'V is. A, ~ log< 10; T is gel cnnccntratioawhcn := 0 '(top ef~ thee gel); ae is gd gradicnt'.(9T/Gr): andivaltagegraduent, is taken as unity: 'j lhcsu~ggcoti- that.grF gradicnts rarl,, 1 k
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is 0.5, timcs tha rIc-0ian pore size led to the square ksccnltation, %T )7). The effective per unit volume, gcl conccntraticn: tsntt cross-linking:.. /Itlseyclcanbe by changing %C.:.to 5 bC) yields~' which th'ee frae- )b'Icto a macro- /, dcpends on tssoa '! A high, percent 125 %C or more) I fiber gels: ' whlieh .i' e,pcctcd'toap:- t•'d vhich escludes :lie basis o5molko- ;'51). The eRective ydrated poly?cryl• 'q.. 1)' alsq depends k'ing': /ow(I to 4) ~thickncssa of about to Ihatt of eross- Bgh (15tn..25) 4eC0ek' Rber: (ib'ou9. 3 jthat ofslarch gcls laftotn (54fl, with 'sibfy duc to 'butn- :en brcakao at'.the kins~ Estimates. Of Ined by PAGE and 1 reasnnab)cc agree- bmined by iodCpen- ~5). The dimcnsions !lamide gcl are Mm- 'a cross-l:nkcd dea- ir pol)mcr conceo- Fvcral workers have k (gpI concentration kleae widk spectrum 'singte ffactionatioe ~ theoryof the be- on both ptolcculcs' Ir gradientsh'asbtmrt Irt possible to predict ~Clocity for anyttsd- la function of'titna rs i~+--~oxp(6L)I-b~i. I an. (1) ) (LT. i ~:q'. r~'la~ trme; r is 1iM typ no is frec.mobilit)C In is gel'corsccntratioF of the gcl)i a..ia i an1 voltage gfadieal Il ,that.gel grndi¢nts Cat _ _•c tuQmlcrutnmmuiecatar wci/;ht, (;IL580. bascd on concept of a"twrccpptarsinval7d (S9): Gel.gradc:cnsarc.not ad,antageous forthe frac- to C of o e Iwo„or only a fewI-1 sp c a (59) whcte a,uniqyre r.unnal.p.ore ean be d<6ned ((0)I fiomwc,:e gel brod.ients h'avcan importantt pat<nscd application in, tha "finger pr,:r.:ng" of multicomponen;sysiemsUru•di~mcnsronal maeromolcctulae map• p„v,r'dS L'. 60L , , ,.uSChemicu1 Use of PAGZ RrlJaroerrhips benvecn rnnb'illly„ grl' .~ ntnraioa; utrtrlrndmsiie nnJna ;, n,e. Lyuatic.n I indic:oCS..tAc reiation rcliti.e cFccltophorcticc mo- P.t, (Rrl; s,-h:ch is cqWOl to ab-lute mo~:bn-M. dfvCed by th'c.mo6idl~y of dyc.urothcr narkcr (/0); tl•; frce clecurophoncti¢ mohillty dfn„ -Jthe fraciionall volume available to tec n,,.crnle C Several: alternative, in- terchl-geablc cxpressionss are given, for l; a, opwhieh involre a negotivic enpo- n:n-l, term, and mvobea p:.r.meter ahlancterlvlc.of the gd (L=Y7) and ~p-mreter ch,,rzeteriitie of thee mmle- cv+; unuar study, 1$/ri--(R+r)'1 or a can,bruation of thcse 1:, (lt }', r)1(10)Itrc • ~ i.ng frcc sacclruphoretic max- bsb,hy 'd;,`in tc:mr of net chacoe Q, R, inJl cuumtrrloni radiurt!row:htfie:usc of equatiotu- of classi! cal electrophorai. (thcc term, in.sq:paree"o:kets in Eq 2): oncis ablelo cx- ,,. mohi4hy in gel clecnrophoresis e`'rly:n Icrmsof parameters of: the gel,. andl b~ufier. TGm of thl:r sult i rvolves many, ~- a'~o:.:,.,,dnpprox;m.~,tlonr (!0, f/„7), R _ hr _ A1., f. - (f SL/4)~. - ertp {7:. T(WS:.10)}: u+ n h 6.~R (I+.(r,+.2~)I~. %~e.p f-.IR+r)'f T)~ (2~)'. tc9athe~ mobility, Rr„ i; :nca- •LCC IA ca¢h of Gvee or morc.g:cI mo- ` rct.oa,. a linear "Fergusan-n p1oC' l.f lur ~1t',v rsur T( F"^: 4)) can b~ -tcd (st)~ Thc .clopsof IrSs Lrv- s ~ -rcrc~a moI<c~.rl:u.size (YOq,il~ 89 E ++. 2 I 11 5 1' 8 10'12 15 20 6.5 %T 0 FiS3. htedian pore rndlus (R..) asa function nf;el coneentration (5b7);,d- o!F:w.ceu und Morris. (3); 4.C= dt- gree of cro.uhnking,. 54,6/; 6.)land'dcsignatcd (f0)Ins:thercrzrdation eoefYicicnt, Kx, The antilogof, thc-y-iistcrcept of I this IJnc (Y„ = R/, whvn Te0).is.a mcasuce of the fr:c ehlctrophnrcti¢ mobilily (10; 11, 54, 62)) and lhercfnree of nol-chzrge (valencc) (1P). For g~iobulir proteins; thero isa linear relntionshipp betwcen (Ku)!"and molcculer radiu:,, R(!0; l l); which hlasbcen predicted theoretically (Eq..2) and cor,fiirmcd experim~entalt.y (Fig~. 5)) o.er, averywlde range of cond:itions (11). Fromm aknosvl:dge of trcc mability Af„ (calculated from Y„) and. moF-udar, radms R (calculated fromK,;):one can calculate the ret charge on rhe mole- eule, us:n el,assical Ihaary,of clectro- ph'oresis (Eq. 2) (17) Thesecalculb- t-nns ha . b'cen comp tcrizcd: Rr valuesfor each cN concentration nre cntcred, and radiusR,. nnol-cullr wcight:Alav., frcee mob5liryr Af,,, and. valhnce V urc provided v,:ith theirn 4S9oconfidcnce limits (11). The precision~of radlun and me,leeular wci'.xh't estimates depends on thc numSer of'standard proteins'used luconstruct thc calibration cune, (;C„)Nversus.R6 and'may.be.im~proved by usc of evpcrimantalllyy determined vaiues (instead of assumed values),for pr,nial spcci5c volu . ,hyrlra;tion, and s-al roiloO1), and by tmproving thee p,-sron,of K,, The Intor is achicved by ' inarcusiog , the number of' points on the Fereusun, p)ot.or by improving the preeisibn of the R, measuremene Thc lincar relation b'clween (Ka)st andd n otecular radius is epplicabkoniy tosph'er;eel protcias in a long-fiber geLl For dcnaturc[ "iandom coils:" the ndlos of . gyration R, ii proportional to (M.W,)ii, the effeetive surface arer is proportional to,Rl.W, (63): accordingly Kn,i.s linearl) , rellicd to M.1K Ptotcins treated withh detergcnls such assod.ium dodccyl su6fate (SDS) form ; rods or, random,coilswithl nearly' constant free mob'ility, (Afa and Ya)r Accordingiy: forr a constant gel coneent4ation,.thare is a linear relation between logRf and mo- lecular weighE (64). Whcn: PAGE is appl(ed to.an oligo- mcrit4scrirs (5, 64) thc rcictionhip between FLW; (or.the number ofsub- units), and Kncannot'be . prcd!eted un- Icrs onc alxo defi'nea a model fon the quuternary surueture of..the aggtegate. If theoligomers.arc. a lincar array of sph'eres (beads -astring) (50), th'en surface area (Kr,) is proportional to nhe numbcr oflsubunlts (n). It the sub'units eoalesc. intoa'o cormmmn sphere, th'enm the surfaccanca ('/:K) is asympuotiaa!'y, approachiner.`~ Closely pael`cd spherca willl give an, intermediate result: A cdosely pack'edd tetrahedrat tetramer will have essentialfy, the same surface arer asa lincar trimcr.,The relation between Kr,,and M1W, of xggregates is influenced by the ellocti:ve radius of the gel fiber r, especi.alfy when one deals.svith species of lowmolccular wcighq.or withihi~gh '<SC:. Gels consisting of points nndomly, suspended in sp,acc are, in theory (10), sensitive to the volumc of the moleculle under study..Thi: suggests t•hat.tAese "O,D"' gels (10)) should be used for, ddtermination, of aggregation state,, since the volumxof the aggtegate ispropor- lional to the nwmber of'subunibirre- spccaivc of~thc quaternatryy structure- In addition to Ihee abovee relations based on the Ogston theory (4S), anu.mber of empirical Irelationss hive been proposed and used for molecular weight dClermination by. PAGE within re steictcd rane^es(47,. 64):. When R, is plo0cd' versuslogM-W:, for nucteicc acids orSDS dtrivati',ves oCproteins, one obtainss an eacellenr eorrelation (Fg- G)'.(d, 64, 65): SD5 virtually eliminatea confiormational and charge dernity,d,if• ferences among proteins and ncduces lhe crtecl of variability in.partial spe- cific volume, hydration,, and asiaitr;rlio. Th rc is a semoidal relation benveea the parYni,bn eoefficienl K„ and log. M.W: (or log R)(66;.67), reprecenting \ I 0
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90 the in:e~rrl ofthe probability dcnsity functinn for the distribuGon of porc sizes(10. 49, 63). Thisean be aoprosr rssated~ by a straight line for a wide ran,e;.resullin; in an apparent linear relation betv,een K,, arsdIbghi.W: (66-68Y: When variability in free ma. biliEy is rcdcccd by SDS, the Rr is pro- ponibnad to K„ (10,64, 63)resulting in alilncar, relationship bctween~Rr and log M.W: A qnantirarive approoch 'ro liuofionn- lion by PAGE. Sinco the usual appii- eation of PAGE is fractionation; one may rcb.vd Cdct.la0ion of Ka„ Yp„ ra- dius, molncular weighti free mobility, andvalence as an op,lionall accessnry of PAGE (d'1). Hbwcvcr, thcsc parami- etershave direct bearing on fractiona- lion.,lnspccrion o{1:, snd1Y,; valuus allows one to discriminate between fracliunation based solely on ~ charge of Kn. Ye, ^nd prcferbl~, R I makesit povsibleto cadculate thegclconcentta- tions for maximal scparation (T,,,,) and for optimal reaolhtiom (T;,„) of the componentsof, interest (10, /5, 59). (Eq3T T_.. = to$ , (Y, K,/Y. K:) K;-K. 7.n c log,, f)'. X,11 K,') K. - i: , or rA.-n linn on a Ferguson plot2r parallel (IC, ,= K.); application of Eq. 3will I usually yield a T_ or T.t atT= 0in additibn to thevalue at finite 9aT. Zcru gcl conccntration~ mayb'e approzima.tedin practice by use of 20 ^.oC, 3%T, or on ezperirncntull,v de- termi.nod (30J 31) minimal-y restrictive pore s;zc Fractionation at 068T can be carried out by isoelectric focusing on isotach'mphore¢is (sce belbw) as weBIas in PAGE. The fractionation of co oligommric aerics presenls a special ease ofehacgeand siic antngonism (17, 32, 64, 69).1 But here the option of isocleetric loctu- ingis barred, since in this case the pl'sof~all spcci¢s are identical or very, similar. F:no.vlkdye ofK,: and Ya,mal-es it possiblb to predict the instantannow vclocityand position,(R)) dor anynolo- cnle in a gel gradient(Eqa 1) (59), and therefore to determine whether a gel gradient isapplicabie to anyspeeified fractionation problem. TheKa and Yo,valucsprovide a suf- fmient. rigonous,and semitivccriterion~ for testiogmolCeular identity and (5) ,vhcre Y, and Ye:,andiKt and-K2 amtht Y,,;sand Kp's forspcci¢s-1 and2. At the T,,,, the average mobility of thetwn speciesis approaimately equall to I/r' e 0.135 times the mobiddy at tbcpoiov of ihterseotionof~ their two, linc~ -thcFcrgusonploti One should attu:npl to optimice fractionation con- dltimns by sclQdfng a~pH such that sep:,rmions on the b]sis of size and of charge are synergistler (parnllel Fcrguson pbts,conctant Kx). fracticnation based sol?ly on sizc (inter, secting, Fcrguson plots, constant~ Y.), andfractionalion based in b'oth (both Kr,*s and Y„ivarv)i(61)fInanygiven cltctrophoretic system (pH, temperatirre I(K, - K,)(,Y, - Y:)<Of If fractionation proceeds undrcr con- ditions where charge and size separa- ubnsare antagonistic, (T), ionic strength (I)', 4eC)1, knowledge (I K, - K,)(Y, - Y,)> 0) `!t 660 tuo Oto 8t d.i0 aoe 006 0!01 not 0 2 e 6'. gq 12 N le I!. 20~ %T aCRMYIOt OB 07 06 04 0.3 Fig 4 (left). Plot oflogR! rersusgel eoncen9ntion T("Fer- gu- plot'): System B(VI ), eonsisting Of a aep-alioe g0 buf4er~40:3750M uis;0.06Mhydroohlorieacid), a atackingtel bu@er (0.058)Mtris. 0A320M. phnsphoricaeid): o eathmdie Q2 butfer, (0.0547Af tris. 0.0546Afglyoine); and an ancdic buffer (0.0625M tris, 005A4 liydrtxhdoric acid); 3%C. Frastionatson by: PAGEof bromphenolhlue (14); ovalbumin (d), bovine serum alhu.-nin fBSA)~(f0). andBSA-dlnner (16). The slope of each lineis designated asretandation coef6cient,K.. Fig. 5 (richt)- Standard curve for the esumation of molecular .rze. The abscissais the geometrie mean radius R; the ordwte lstbe square reot of the retardstion cocRc?nnt Ka, hlolccular s;1es arc, in scend"mg order onthe standard curvc, bron•henolb;ue, rnyogJobm, pep.in, rrvalburnin; hemogfohim, f15z 1tS:1-d-r. Bbnxcoeen, and'thyrvglnbirlin. SysremAttY)d 59cC. r D:I O[ , 5 _4 -3 _Z 0 ^ /7n I / I 1 I I I I rvtl I O t 2 3 4 5 6 7 8 9 Hnm
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91 tson plotars aion of Eq: 3.'' - ; or T,rr at '` 'lalue atfiniteiionmay be' by usc of20' ilnentallyy de- Ily restrictive 0%T'canbe' I' focusngor b) as -ll as '' la oligomerio bse.oUchange 1 32, 64, 69).' blectnie foeua- this cue the pticatior very I " ~I Yo~ makes it ' instantaneorss 'for.any mo(e- 1. 1).(59), and vhethee. agel Iany specified . ;zncity. Thc-: probability Ilhaa:l,vo ..i,-nt molecules woulW exFihit:idcmu.ai Ar;.wtJ Y„ rJuesa( thnt•J,vergcnt p)I -laer fs infinitcsi.mal. PAGHthus. prov,dcs the orW)tcst'.of~ identity, that an be performed on microgrmn nrno.unts of matcriad, in hcurogcncoas .ntuns, with, sensitivily. lo mihcu- J1pcnJcnd con(ormational chnnges and vatlon ~ of~ activity.. '„11, , ,,.,lving p.owor of'. PAGE c:m he t~pantitatively us,assed in any, par- ,c •+- expcnmcnt~ byc:+lculstion (F.q, 41 ot, Ihc number of,equivalent."then,_ r cal pl0t^,s•. N. (V0„74'-72), permir.ur:: comp.irfsnn with othermethods.. N'_ ~7,ls'=.5.55 ..ri/ tJ (d) s the migrztioredistance: n, is thc •.tzmJarddc.viatimn of peaAwidth: ard' ~ s the width ofband at,0.5' (na.-a amp,litude). In free clztro- pK~nn;alt iv powihltloobta:in 10(M) or, morc Ihcorcncal plales (7?I! Asimilur nurbcn nf"plLm~s" c-beobtaincd in pcl dactrnphoresis. (71): By contrast. pd 6i"r ndon os subject to thc binomial . amce ofany. partltion prt+ceg.' so Ih', I !v, vJluesurc u.uLily' bcldw I00., and rea;h :,, maximum, of :rbout 7(q' •dh coLunu;s I nncecn long (6R, 70):- R.6:, r. a!-PAGE.rmorhor.pln.+4 Llnlilcscdime.ntation cqui iurr„nn.. I'AqiL dac•s nou ptoviJo :ur nrolcc,dur wcrgh't. '+N~ ,n i thrv re,p~el ~ il iisimilar to oihu r ^rr ,c i. nt,of olccular size (get tomtrlm -cosrty+ ltghusc~t- ~r s d mcm. c o eioeiu} d:diRu- .•enlwhP.hare sonsitive to. milicu-dQ- P"Jcnt unturmation:,l changcx: In aJ•. PsCE - betscdt. m rc rrt en et.e~~n) . pH and Ihus too eom r•vr' t crat".n" e.rr,esI1J7. Thcra is s rcInor hp betwccn.the ratioo u sr iPAGF.onI'.the prrtion cu~ e'~< t h c I lflt •uion (lct, 67)_ ~mcty-livc ~ purocnt confidcnce: linrlts rx""'t,J tor c,tiniatcs.ofi radlus and. ~~:cullr, wci,-hr'i obtained byPAGE 'e•• app,e iule(11., 13, 7J); How'- ~w I c:l t t I)~ t q. . r.~ ~ . h,..,c r been u u I). . p. ph s'-1 hem cil th u.ircct compansnn. 06 M•r.:on t.not arailabLc. Hov,:evcn tAc H'rr•~on,o c>tim:ati, o( Rnnd %I.\\'. s~ .f cl.:rr„h.hnresi< a.npcar at ic.aw ~"r`n 'ro'n ga rtitration (11. 63) ~ ,,,,n,l ;:ornion Ur,.e' 9qCiF is h'aseJ or. ' •'anJ .r,eurate &,.meaxr.re- v'~ 7n•Yr• ncnarrnwau . 5t ~ . h.n... nxnu ocnend,~on atartingr zone wiitth„malGphn,lc hufi'cr s)ztcros arcclearly advxnt:.gcouc (1),Aecur.~¢) of inea.uncment n1 ndgraairm Jistancc.of nce, front aaJ Il:rc hanJr zr,J of the.change in geL length Jhr~ng stonn- g; lir-eclyJctcrmincsthu'.accurocy,ofRr (/./)_.Trfcrefore, measuzcmend mu,t becarrid out with earc; rrcferably nn pirot cgraph's {I1yor byy usc of densitum- etrrr (71),cvrve analyz-n: or cums pa:r::tDn. ProociAs can bv fizcd I in trichd••ror acetic. artid (TCA). solutto:nr (74). in amddo~black in 7% acetic acid (f6): or in methano)ic solatVon ((55)I Nucleie' aoIs and acid pd.Y>accharidos cannot hc fixcd'' p;crmancntly; ntthough15'.! acctic aaid-1 Sa l+nthanu-cetstc has been used (or that pucpose: (73). Pro- tei'.nss can,be stained by,Cuamassie hlue. (6d, 74):.amido, black (16);.(ast.green (76). or• the fluoraccnt dye amin~o- IpT 0 --- - naph'thob Ifomka:id (,7).. Quenc`.:in~g ~ ofifluoresccnccp,romiss to b'e a sensi- livcJctcctlhn luot (78). Nucldic acids can tlestaihc,i bymcthlylMeblue (8),., toluidine bluc (SL acrislir.e.orange(73)lc doublrst.randeJ nuclcoGJcsi mtybe de-tcctcd fl'uoromrttricnt!yby ethlidium b'romide: (79); PalysaechariJe stainsin- elude periodat-Schliftreaaqnt (80) aad Alcian bluc ontoluiWine blue (75). Den. sitomctric hz.ndd quantit5tion ofproteln banJ>(76, 81)iis fcaaib4c after amido:- blackor f-al igrcen stalning, and elc<tro- phoretic destaieting. lJnstained poly- acr)lamidc gds cann be subjectod to ultraviolet dCnsitomctry, f or nuclbic acida (34), but Ibis is just.barcVy'sensitive cnough' for p,rotcins- at conccntratiors comparable to those required forstai.n- ing (82). Alternative mel:hods formea- suremento4Ry employ cnz.vmatic(J3, 83), immu.no6og:icl!(34-56); or biologi- \ l I \ l l 1 t= J \\1 '1 3.5 3,0 2.5 ~ 2:0 L5. 0; or a J 4C5 )Df 01 5 10 15 20' M19ILITY,CG'z-V'pLT-(-SEC-1 X'10'' Fi^6: Stan,;.+nJ r rve fc.r the. e>timn:ion of mclkcu6arsi >(.1. C. Peccuckand C\J. n fi^~rc.1 in (5p:. ?hle -,hse:..a rnprx _ o~~hloietic mob'il,ty{ the ordirz r te. repr~r • cular ,,h :. rlim,Jc'^ ci 5 c ' r,n rvn eh., S:Ieristic fDr c: I:.d in the 1 A gaSrro~ . c e nuaui s~lf.5r.e throueho.ut; RhA' s..r cl,n.,c ~ e ctcJ l!-.y szJn' 1 t~,~.r c~•cr" ~en4s.a e(ractiona:ed. ECo/r l6S' Y b l S 1. 1 1 ~ l. 4 ( F.CaI•;S ECah'aS~ ~ )D~0 1 I ®
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92 -cai (J'77: nsray' ur isotopc unatysis aitor e3lSor cramsv_crsc (EJi..3S) or longitudi- nJ. (35;,86, 88)sldciegofithe gel. Foractirity measummen7; the mcromclc- culc(on iu.lig,and).may bceluted from' gel >licis(15'. 85). a~ srn:,ll substrate can'n diflu,c into the gel for.enzymati¢ assaygel sliccs<a.n be.dissolved in H.O1 (89). ctRyl:ne dl:,ery4ateeross-liik.ed gcl, c:,r. !c diuol'v.d hybase (J6i,491. N:N'-d:~liyltartardiamid:cross-llnkcd gels. o)') perioaat¢ (9/). Fur isotope a - ysh', the materiat in the tands may'liedi:7used tntoNCS reagent: (Nuclezr. !'hicago): (53:, 90);, Hyaminc (86), or, Triton-Xa00~(9:),.or gcl homogenatormay be su.cpcnd'.cd' in, I nstagel ( Rack- arJ) . (JC). Severall gel >liccrsarc usef ul: . wire slicers (33)',for5to'15: %T gelc, bladee cutters for solidly' (rozen; ver,v sufl (loH. S:/T) gels.or very hard (>15'. S°7)igeh(9P), and a no2ztee device' (99) tort cslrusion o1,lhc gel which lcnd5, itsclito the automated processing ofi largetrumbcrsof gels. Thc precision af'. R, mcasurement':on gel sllccs(standsr& dcvlStlon of. = 0.021 is:only twice th'at, fhau.l fur staiunl gcf, (YS),. Originally; PAGE was.carried out at either very iii~ghl (1. 2)) or~r vcry' low.'pH (94). This ansurcd!thal all pnotei'ns' mote h lhcmmc dilrection, but, minimizcddifferences in', net, charge and «duccdcffia:ency of -charge.fraotionationY (61); It isdenirablc to perform PAGE at: scveral'.pH valucs to.optidnizc fractiona- tion.. Freedom loQ opcratoate anyy pH; . isIcyuiredby, t}iepH:activity, profivae and~pH-stabiliycharacreristicsof pro- tcuns; and is necessary for homogeneitytestingy and' consttnction of "titrwion' entrves: How.eveq, pH bccomcs almostirrclevant when PAGE is applicdd to tnoleDUles with high, fised charge.dcn- sil)^ (that is, nucleic ncids (5;:8. 34), acid neucopolysaccharides(73). orthe SDS derivauves of protciels (64, 65)1. , '•Conrihuwu•' versrr.r •"rl;uanrinaous" bnQer syrn•.ns..When.PAGE isearried oou in a cont/nuous' buflcr, (jvhlcra th'ebwffcr is thee same in the gel I amJ ~ both cluctrode chambcrs)) pH variatio, iis read,lyobtainable:.lt havomly recently bucu:nc p,n,ihtc.lu'.tnc PAG&in d'.i.cnn- <t1rY32~r rw1G4P1100n U rU•Aa 05enuNUNBEtl.• CMRAMBACN5S YDe • OEaTENRERAtU4E• 0 DEG. C.. COIsIJrUGNI 1• Nn. 2< . NElEs' COMSrUrUENI 2• rW. 20 . C1600YLiC ACID COw51n/11EN1 3- nU. 99 . CrtlOR10E - COMSiJIt,^ENI A• 60. ]3.. BISIRts vNASES ASnnstll'2ETA/41. BE1At2) P1(asL1HaJS(B): 6sa+at3f. CI D.0<00 O.D<OO'0.0256 C2 0:05:9 0:O35L cJ0-o4a9Ceo.o3s] o~.osseo:0)or` D.21270:22I3o.zl6t rYElaC.JSn 0:396 Gwttti o+is2 0.1.50 •ntlil 9Nlt)1 .Nt/61 0.318 0.)1A. F>ttl)'. -O.o<2 -0.042' xNtzt'. an1)1. brtl6l. 0,144 0.1<i PN 7.16 7.10 EON.51R. O.CO60'0'.DO>D SILhA G-la! 0.3a1 alO.Y 96.. 96. bu. -0.tt^.. -allo ar O.I12JOL02o 1Ig: 1 i p. ctati ~ co t r n r ~~ohipr '. m ffe~ i ~ted on Jo'.w (IS). -..e.tr I° n. the k' -r ~...~ t..fhr m I - u t . .1 J n 4 t.,.d N1.1 - - v mc.o ._ t . syn .•.~ I t c 1~ y ~-. .i J S .i,_ ... p uaag,les rceusn, a,ln[e. ~ ^ f l8 s er b,ru)ry.J- ~ ~~'e^` -.,. ;~,le.'gnateo'.:u~- 'ihe s ing lim~~uo4'th,s .~ut ~sy,temr:~n~_-. . RFt', 11. 471 t (.. .•ltalu;+lerstacl;ng Iimit ~, Rll (..'_)I. ..a,io.n Fe: wiJ f, pe.iee. ~,.ah a-el]I,vc m~vhilitv h'el~Ow .~t'~t~l. =-~ . Avarnstivesucer,g I:Ir_;:• arc asuannil:bie from c„m.pattr omptn~, C.5o0 a.)O< 6.320 g 4.a23 ssi bllBo b s Thi th k it ., anC': 0.472 OLSiS O.^bh a rs.. ss eoryy ma es po , prcdict,.on thee basisof'the yX's and' a 1•no0 ionic mobilioies of the buffer comtitu•~ ., CLah3' 0.071 0.152' 0.20? cnts: all lof the following parameters; the ~ j vclAcitics.of all movine boumd5ries 6e-s .,.1 -c.zsa -0.164 . -o.su : twecn. phases„tFeconcentrationsof all'{ 0.320 0.02T O.OS• -L626 0.OT9 ionic constiments inIhe buffer phas6 on either side of the moving boundoriH i 6.15 0:0259, e.00 0:016e 7.62 O.0J)9' T.66 and'~pH;.eonduetance; and bu@cr value i D-D+a9 in each phasc. A computer program; 2.2i5 5«. 0.955 =3<. 2.977 T0). 9:4T5 based on this. Iheory, h'as' b'ecn des'd•-, 2201, ' -o.lto-oL:r7 -O.t72 -o:t72 oped and wed to generate 4269 mrslri:,y OLOal o.o4e 0.069 0:069' pha.sie systems operativce in, the o-s1 l des< plle uff the physt.rall propertids of a thodlcc or anodic dircction, at 0-S p thc h,.,c~o4 piz..e- n~.J ph 11 ~ thc. Iheory a ia Jesr^nstcd ted a 6, t~ ta: ~ t nd~~ prograrru o as~constiturn th . -t o tt lh Ul+pe f T. \[i interv'als ccrou.tlie.pH seale„at 0' o 7l t Ii.th'e 25°C (95),.The systems utclirs 45 avall- ~ '~Ih abhb tiuRor constiluenm AA porcion o IS ! r 7t a . F I 1 ' . a /1 tacA- ~s ,. I the.co: puter.oulput for a single mpre- 1 sct; i . , 1 r c ti.. th . ~ wi t~-g , 77 1 .et.. scntative mulliphasic buRer system is,, r" 4 G si, 't t.. d. ~ r h e dc m u8cr showntn F 7' • ~. '"R I0 tinuour(multip,hasic): bufier systems at anyy pH (9S); This makes it possiule to exploit the many, ad6antages of multi- -. phasic buQcr systems:.(;) "Stacking' (f) of molecules in~th'e moving boundary ~. b'otwcen two bulferphases makes it Fos- ' sible to sludyvery dilutc aamples.. (n) The final concentration~of a eomponent inI hee stack . iss independent off the start- imgconcentrmionof the sample and may, be as high as 200 mg/ml I(J, 95).; . Theulirathin starting zones (a6otsa 10-= cm) result.in markedly improved resolutiom. (iii). Siack'ing, "unstacking; and "restackine" can be used selectively for fractionation (see below). (iv) Stack- imgprovides a prcparative separation method free of load limitations (l). . (v) 1.ftdliphasic buffer syslemsprovide ~ a"frone," th.t is, a moving~ b'oundlry in'n fronv of'.the.scparalion phase, which. ean freqwently be marked'.by, a"track-" iiso dy•" ( J).~ This front is cortvenient in ~ followin-, the progress of,ar, experimenE.and im thccharacteriznlionofb'ands i0 ~termsof relative mobifities (Rr). Thie' major disadvantages of multiphasic buf- I fcr s)>tcross havc been that actual PH and other, properties in' the operauve ~' gcl bwftcr arc di0erent.(ronr thoseof thee buffer as prepared (Fig. 2), and t1Jatahesc buffer systemsheve nol6eeo' availzbld ex.cept..at.a.fewextreme pH:~ values.: ~ An c:<act theory of mulliphasic buticr t systcroshasbeen formulated(9S) I b'y~ o>;lensior' of the trealmen4 of movingboundancs for weakeleetroly}es (96),) to multicomponenl systemsconsistin~g o4'rnultiple stron and weakk acids and .I pp! . 11„ , phhnc b•ger.ryl-~ tnruro. /racriDna,;on. The comp)6te; chemk Id. sc.i:xi'onofFench multiphasiel bu:R.r systc,o (Fie. i(lintmducrs a OeW~ dlmenai-o! s'ersaulity'into: traetiona-3
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5SIOrRS . at wasi:.b13 to i of multi- tking- (1) ',boundartg ikes it p~s- ,mples. (i9) ~ pomponentt tthe start-binple and md (1, 95). ses(about yimproved Instack'i.ng,'' IS ;elective(yI (iv) Stnck- i separation Itations (I). tms p,rovide g boundary Ihase, , wF.ick by a "tn.k- bnvenient inn p o(perimenC of:.bands in Cs (ftr): The Itiph'asie buf- 4 ae.tual pH thc eperativc ,om those oU Fie..?), andlave not bcen ulrcme pH i jiphasi¢ b'uffcr Jatcd(95) by at off mnving Ictrolytes(96). ~msconsististg rk acids atsd s it possible to ' the pK•s and mffer consliln- parariseters::the bonndariess be' plraM1lons of a11l j buffer phases g boundarit7. Fd buffer v31ue 'puter prognam (as.becn dn'el- i te 4269'mts1U• P~e in the cl- lion, at 0.5 pN ~'; scatc„at.0' or utilize 45 avarT A, portion of5 'r a single repre" puRer system.k yisres.fa LuBrrays" t. The cornPlr~ i each multiphask f ntroduees a aee! ~ :yinto fractiotsa Ilor,. The known "bppur'• and"bwer .-s_,rn;limul-'• (ihc mubidrtics of' Ihc Ic-Jc., cnJ Ihc Irailing ions of Ihc s's=Y1 o:dow onc lo use slacbingselcc- 1•c;ly far Ihc purp,osea of fractiocation., T^^: w done by scli:ccing the upper anJ Icw.-• ssacki.nel,mits so that they brsc' :' the mobililtyy of, theeomponcnt oL:nmrestbutf are sufAciently•tzrrowto cncl-dc contamiinnnts from the staak.: I-Jm -th mohikities gremer than the u;pcr nacl.:ing limit will migrate ahead o,' th'e.front and~are usually.lost to ob- s;rval.oi: lonswilh mobilioies smallcr tb= thelower Stack'ing limit are nott enrcentraled and give rise to diffuse b'ands that entcrr the separa4ion, get uucn latcrlhan the'•front" andusually oumc:intcrferc with resolution, of the of interest. Proleinss have lower eenaV;.ient:m~ob'idities than most'buBer rons. cven in i Cna absence of'f mokcular maki,ne it neccssary, to-i~ni- r.¢r Ihc lowur stackingJimiti Nudeic aaJi: w0h their high fi.ed charge and Irra mobility, would require an eze.es: s.dy h-,gh; unobtainable upper suack- ~nf imnios in ann opcmporegqlE.b'y. an mcrc-, irn gel concentrauon their mo- b.'.,ty, isredwced bcloww thee availrsblc •mrslacking, liimits.: clOn: ccn alsovu sclcctive unvvaakiirg sr,} ralac[m~,: "Unslacking-" rcfcrs'" lochsn¢c d<onJioronxwhichrcd- tr. uf thtinrscrn-idm, c„nacn- u+l~sd ar a moving:buundbry;.bcio,v,the ..:bdhivofthc bufferions, delimitin^ nc tmoving boundary. This can be done s+ clnngng thc: pH, by increasingthe c•i cc^-rmoon, or, by changing both fIt and'.poresizc. SI!ec:- `reslacking"refers b the DI-b„Idyv of sub'ssilutingg or supcrim- Tti^g a.ceond: 1taiMngg ion on thc . n.4 u r buPfcn to.gcncralr a ncw• c bmumdbrythat' witN avertakc. and accelcrate a slnsvly migrar- ~t spec- lhisiy.potenuiatllyirnportanl t~ plep.-.lve PAGEE because optimal 'K{uuen often~ occun when nel charge a"e^'o~,Imyare small; preparauise, scp- vLO^ woulJ Ihcrcrorc be. assnd:rtcd-rlcd~ dlRuaion spreadine and ek+'sun unlcss restucking.isg empioyedl rhe nue alnmrrF('lhasle ~`~r•+yuemr ic PAGE. Fraetionalion w^V^:nasic 1ie04r syslems dcpcnds ~ uacl~re ofthe conponcnl of mter- ~r lna'n ,: be vcrihcd:by comdlucCm a' conecntrntion g~cl, and by' Wy'r for the:colneidcnee of the staek;, ~+" 7 r..arkcd by"a Irackino dyc. svith. ,e "- d b;nd or acii4ity chamctcr- Y' I° tM. mmponent' (17. 30. , 311. 'r've a6-nc= of a trxkine, thlc fs•.a: O~_ °.8 - " 93 posi~tion of the stack. can be formd by. analjsi..: for the IC~.dingor 1railih; ion. or h) d,tcrmining. Ihe in0'octiu.n point (or the qHlor cunductivity.di.contim,iryy across the stack(V1)1. PAGE in rnultiphnie buffer systemsrcquires p.rallcl surfaces between gel and1 sampli phaces.and thetefore verti- cal alignment of apparatus (1;.1; 97). The fragililty of stackingg gcls p:revenls use of"sample slats•' and re,quives me- chanical samiple partitions on sl2b ap parutus.. PnpanGve PACE Load capariryy o1preparnrfvr ap,pm- rmur.. If conditions for fractionation h'ave been properly definedand' opu- rmized. transition fromdhe analytical to Ilhe p,reparntive scale in, PAGE only involvez choiece nf apparatus, load. elir- tion buMcr. flow. retc; ge~ height, and current level. Load eapaei:tyin PAGEE is proportional'l to the cross-sectional area of gcl.. For separalion of' twoclouly adjacent bands• load should not eaceed. I mg per square eenoimcter of gcl. Ibzccpc for prcparativc stacking (isacacho.phoresis)). In view of thiililmi-. taaion, the wordl"preparative" appiLed: tn uva P.stile appanatus :may imply. e load capacity at the gram;, milligram:, or micra;ram l'nvel... Gnm,preparaaive appLratus has b'een, described (<?, 98)) bua idstill, desxlbp- mental.. cumbarsume. and nol genera4lyavailablA Three smallbr davices (or..mil- )i.ram scalc prcpanlfvc PAGE havee prosed', useful (94, 97, 99); thcp, are based oa a cornmon design (97) ~ and are commsrciallyavailable with voss, sectional arwe ofIS, 10; and~5em". Thisapparatuss contains a hollow' cy- Iindricallgel ring of.up to I5'm~mthlek- ness, with an.outer jacket andinner eooling cofc to provide constanl tem- pcrature duringboth polym~oriution and electrup,horesis. A symmetrical um- obstructod dectrieal'. Reld l and an eh's- lion chambcr otminimal size are pro- vidcdd by a porous glbss memb'rane: (or dia.lvsismembrane) as the floorof the olution chamber(Fig:.g)::Efution is sy'tn- metrical,. with'h radial now ofclution buffer from the circumference to a ccntral cap7llary. Byadjustmcntof pH,, ionicc slrcng;h, and viscosity, of thc elution bu?fer„it is pos.ible to.decelerate rig. 8 Alparcwfpcpar rc nAGE. ld 6n P natp.e (97)1~ Annular bands enrer i,to thc, minimally.s rcd elutinn channber.ar dd are swept:upward into a esntral eapi~llsry hy radul Low of etuuion b:ufl'er (inddcated byth:e arrows):..
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94 I I b: Gd.colan sreiq"t It: Pn. .5ua. Ca3 nrt chhr3e OjtiwuatioaP/I 7. PrtPuatis PA66 f 1 g. IFPA8. SiulySUU-Stas" emtpie.t' snstypeal pr,7arati•ra Pr.Pvti.e Fie-9: Oeneral Istraree for Irzotiomatioa by PAGE the migration of the band, so that thlee proteinisOush'ed from the elution chamber before it reachcs; the mem- brane and islost. Microgrurn-prepara.0iveeulumns based onthe same d4sign (97) with~ cross- sectionai.~cas of 3'and! 1 cm=arc also commercially available. Devices with twoo othcrc7acion ,mechanisms are.avail- able in.tfiis.load range (44, 100). Elu- tion from ana:.ytivatl scale gcls 6mm in diameter Sas- bcen ulilized torr micru- gram prepa:rative purposcs(101)! Thc:,e smaller preparative colunmss provide relatice ezseof'e operation at the en- pcnse of load caFacity. Problernrin',preparatr.ve PAGE.. Re- covcrierfrom PAGE areIbad dc-,en- dentt thle r::•overy has been observed to ihc case frormL0 ,0 90% w tn in- erea n lhad from.0.1 torn per squarc e^_ntimcl.-r of "l and Udefxnd on %T (?0). lot-l rccovericsare fre- quentlj']ower in vicwoflosses dur.ng suYscquenat coacent:ation ~ oU tbc d]luteehats. Ahother prob!em in prepa;ati.,ePAGE i: the eltlstion of a rondialyzuble irnpu..ity; e.hioh iss g:iven. oIIcontknw- ously during dcctrophoresis, gvcs aa pocitivcc reaction '.r. the eolmrimxtricc assaysfor prolcin, and', may be lin'.::r po!yacr lite (?0!. However, it can~be sep„r..%d from prouei¢s by gel fiitratiom on purified SepS'ade.< G-50 (10): Continuousrccording~ ofabsortix:•ce is of. l,mitcdunctulnessb.ccausen-:Li- tr.ree of eemponenugenera1l.y yieWov_r:a?piag distributioa curtvesahichrault in a cominuou.broad doniun pattern; endd bceause th'e high dllt~don t concomitant with'' continuous clutionn of ten reducerprotein eonceo~tratibns be- low deoectab fty. btem, . ren¢nt of pro-teinn cun.cen4r.iou in: duates byth'e f-owryy pnoccd'ure (y'3J I is usualVy p:c- oluded by in4erfeuing rwctPons:of buffer canstituents;, hut analysisof TCI,-pre- cipit:rt5s by the LAwry y method iss pos- sih'le.. Aitalytical PAGE appears to be generally tbe best way to monitbr'thc eluates. The 'high'h dilution of cluales ncccs- sitatcsauailiary conccntrating steps, sueh i ar dial) sis a,uinst vo:atile bufcer . fo;lowed tiy, lyophilizaoon, ullrafiltra- tion with Diaflo'(Amioon) mernbra:nes, or with dialysie:tubing, tunder pressure or vacuum,, dialysis agaiID;t 5056su- % nenu in a stack:.. Sinoe the syathetSe ampholytas, bave abroaddistribuSa~of'ma,ilities„ they. eaa be cSruen pfprovidc spaccrs bettveen any rwo pra., -.; teins. Eldttion of, the componentsn uf.lhi stack, separatcd by spacers, sbortld be' possible.within wide limits of load, will;Icssdependence on gel suffaee ata[ ---~- than in eonventionaliPAGE.. Isoelcctric Focusing in .1~ Palyaerylnmid. C.eI ~; Parallel lines on a`Fergsuon pld' indicate fractionation based entirclyty molecularr net charge and tSerefmse~ optimal separation (1, 11), oceuis if "zero"' gel concentration, that is, ` free clectrophoresis,. ineucrose tlensil}~ gradient electroptioresis, or.ir; a gel wifh_ anliconvectant but oo molaularsievi4 propertiis. When thiss is encountene{, isoclcetric focusing is tuually, the 1n>" tionation method of choice.: Isoclectrii.focusing in polyaxrylamide gel (IFPN, (30, 3)„104).providfs load econorto7; short running times„ and opcrationsf." sin,plicity,.Ttr_ fact Ih'at, most protc•iMy p,retipitat0e at' their isoetcetri¢ points 4 : (p1) isdetrimental whenisoelechS~ focrusing iseonducted in sucrose soitF~ tion but is turnedto,advantage in galY~ Unddr eondduons of . molecularssn.- ing„migration of proteins to their Iso~aq~ el-_th¢ positioms would rquiroverT:. Ione, times, Thus.1FPA' should be eoo*: dJsctcd at the mi,nirna1 gel eoncentra•tion that providesadequate meehmsia stabildtyand wall I adherence.. Mechaa4~: cal~support of the gel and hydrostak cquidib'r,.tion ave frequently, desirabl4,-a crosc, saturnted ammonium sulfate, A chemically', stable a11-glAss upparatm_ Sepba4ez; Aqyzeide. II, or Fieoll or , ith.good tieat transfer and bydrosta5oconcentration.by,electruphoresisinlar e equulibration properties has been tlr: s¢:ii.tggcl.s.(d0I)i v ieprd(30) for thispurppses fso:nrhopAorcuis. Aprounisiirgap- praach to ~ gram-prepamtive PAGE ul'7icss stcady+sta:c-stackiog (1). Thecempnnentse of thee sample are sub- jected,toPAGE.in astacking get andd are e]uted in., oriler o6 electrophorelic mobilit,vwhile still in the stick. Fraa. Yonxtioo improvcs with incr aang Ioad,e the. di:tance- between adjacent s:aa1.ed'' componentsincrcaies ass thalo d beccTrslarger Sincc tit¢aon;cn- Ir tir,niofi ear.;~.eoneponeot is rcgulated (1): A' modi6cction of th:imelh.od, designated (103). "isotachonhorcsis,"is of consiucrable.interest.. Here synthetic poiyamiropoiycarbatylicc al,phauic- am- pl4olyrcs: (AmpholEne, LF;13 Pro.ctuktcr) are u-ed!. as"spsccrs"; w•ith mohilitles in[ermediate between proteincompo- T4,c isnelcctriec state of proAeins b- best recoooized: in fFPAby a timo~ - stability. of the band pattern, doriafsseveral hours; Usualilya period'oLgb* I1 hoursat 40 volbcm, (regulated), 0'C, ': su.Ticient for the attainment W "isoelectric endpoint` positions of /hsibandsin gels of 5 cm langth. •IherateL at which buear pH gradientsand asyrrtp•.- totic values . of specific eonduetance a»'' ob:!ained aacnot'usetul guidesto l~bt~~rccognir,on, off the isoelQctric ecdpmat ~. (30, 31)! Theb'and patterns at the i$o-s electric endpointand pFI gradients!rs, un:•tables.ith time (30). TbisiastabilirJ-; can,be sigaiGcao.dyRductd by, the isr,~ corponation of 1,to 25Sasucrasl into the gel (31),for some Ampholirr~p ranges.. ln,tab.ility of pH gradientsvstar, si:.. u~,Y of IJ_;ritc~ ~,
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95 Ap,,ndic usOn p1R'q m0ircty q 'therefotg.oIKUA ,~ tbai u. ~,. deasff}' . in a gel w* ular sic_v~ia# .: Cacoun(r..etl y, the kagi yweleeClG.. agel (IFP/1~ d econat~r opc»tia4lfmost prote~i%.~ Ktric y.r~t n isoclee4ti . suoroso w~r.a'' ntage . in yv oleeularaieF to their 1rP require viej.' hould be.0ad~ gcl conatftii' temechaai(>i nce, .. nd hydtoftaw ntl)•, desir'abla L4ss apparl"• . nd bydroam* has. beets rt tpeseo of protritg-.! .. A by, a &0 Pattern dit" ; period of 1.r pm, (r~at!~ .. F atrairt.'tst:at~d oStttOna a~.-~.' n,gth.'Rte ~'fenu amdasM`'eonduetatap !t ~rp guidla~t'0 ~r ekctticc cac:pr~ ptems at ttre.10 H gradieaKr~; 7ttisini lduced by' dM 0' t ~° 23 fia st10~ Isame Amp < 7H LT*dit:a~ 04 ;tp ;2< lollaxvm: abbrc.iaoons are used: nht sct] aradiena - a<rrldn,iecm anonuionYw/v) rcrandvioncorMarna: (E,Sny) r:a Rr s".nuthylerrcb-rrlamide concenwation (w/.) Ry roz.ainknnz _ Bu/(AT Bi..) 5. niy SDS fraciis,n~1 voluma:a.vil:l: to m~lecuk rstekerrie focusina rn polYpcrrhmnJl.e-t r' neh' T p:~liunnce«Rei-t (S:) ' T rctarahtlun ~cnetFcmnt2 a.dat . " t:fmr sprcids 1 r.~tarJot~i,.n c,xth~mnt for st~ecics?. Debyc-lluckkl rcciprocal th,ck'nns pL 6T lanph (cm). oCsel lfib'en pcr . uAt votume (em') dcct/opLurctrc.m~biLty.(cm ee. 'volt-s) free clectropl,oretic mobdity' s mnlecuVar wcie4,t mbrr of'subuniis,ofan,olileumeric aeries, untbsr nf~ Iheereucal ~plite ~qumalenu pul:•acrYlamiJc sct. ckLvupluorcaissacl,c cpo-i muleculfrner charaeM binty rclarire to arbttary, iauf (or vuvine rno rnuneary) t rx.iw~ of mawo ,on. r,ute lo the- nonuni.'umm distributiocof nr.ently avzilahlaAmpholines acroesne gc' wrtrch r sults ina relatively earoszJ. conductivity'of the gel centcr ect'i+ny and p,H:ean bomeosnrcd on :ye idenli.al IFPA gel sl:ecs (31. 106). t.e sn'n.ng9 prxcdums of AACE can se =pN'cd'.if amph'oly'ics arcprcvioucly, •.-:cvcd w.hh:a u!tlTmiunt-d@sL,incr cm+- ..r,n Pnutivc (11); . altcrtuatlvrlY, pro- _ vbe st,in¢d by aprocedurc wrumvc to . amphol'yle.. (107)., ..fttr b•t.on.in TK:A, prccipirtate bands are• ond ::!Ww (cn utcctdve slici:nq of 'vs bmdt: c>tractbn os protcin,from "'. sr,;est a iow acida analysis (30). r--rasalivenI o mFPP; on getiwitha diam,. ^' o!ISm can accammoSateas eia`b-s2~nngof protmin per bznd1(90); as t -U of 1`AG4: D~ hc: tho d' cr iay. of ap lioatihneL~ P tiG17. i,: eral stralcgy~ ean bc ~`-v+?cd (f;ig~. 1). In~ this~ discusaion, t" tt"poncnt~ of intcrc,t will bs rc- aC~ tn~ ar th~ ~ pr t~uni altlhou_~n it oth chargod mol~ ulc, Cu- of st;:lkia.e: A: an ;a.mplei is.applled to.a tc 1. ::nl t)c f trc . ' P 's, n:-4~~c in~tha sta V,.~ dc A'I_r t ci:ing. has bee -ri~. .rndIlcnccrstad.-n, C,:Its ~' -'r~.vrdrto~on:tzon ash much.sclec- wa h,c ~ r~ oE st~eking: T}ic~r;H~, ' t xrcu e~ .. ~. g-.1 t.. „ticd ekctrophorenc mobilityy rtlatire to. Na• ndius of pol9aerYlarrude tal nber ndiun of ~coomtcriom, radius ofayntiots Stukei ndiua w.faa radium 6udecYlsulfaue standard'dcviatnn of,peai Hdth time temperatune totallpel ro cmunr;on (T=.A+Bh)('-/+). M c n for mal scpara-e T-c 'ad c ~oprima) resotution, TCA uichturoacecic acid~r Tc-AfED A',N,l.",N'-teuran+ethy(eNryknediamlmT, ari e - On top Of aet clmrophoratic mobifJp, q mohhiluY at r-, u.ecl c rnuatiea . ayi m bihtryof tlx'4adina ion iathe opentiJe mo upara;ion Dlsax vctocity, width of trak at halt-rnaaiwrsa seicfu v/r welrhi (.clume)-'distancc X,. (e RJ Ftcnry3 funetion Y; Y; for spccii. 1 ' Yr Y; for snceirts2 Y. R, when T= 00 systematically to determinee the pH rsnse avai.lable forr fraotionation: Thiss can be done by.changing buffer syntems;, or by modification of the buffcr,concen- trations within any one systom: J) hfacromolccutar, mappi,ng;: If the pnrposc is to obtalb a macromolecular map of: the components, fractionation .carrlcd ouu in twodimensinns, one of' whichis: usually porc-gr¢dienL clcc. trophortesis in either a slab apparatus or, a, preparative devlce- d). Fnrgvson plott.. At a de,inblao opcmtive pHl. a separatlon gcl is Se- kcted in a system prcviousl). •..x.nn to prav;dc soioking. The prctcin is.fra.- tinnated b'~y.PAGEat five or more pore. sacs, with a oonstant pcreentagee of: crossdinking: Nominal T values arc cnr-rccted for the degreeof completion of: the polymerization rcaction..R/ andT vslitsaro- used'o to comp,uteth¢e stopee andintcrecpr of the FerFpisnm pl6+ts. Kt..,Yu,,and. thcir95So confid.mcelimits (Il). 5)', Dclccmination of molecular sizo mJnet charge: Ferguson plots' zre, ibt,enedd for scvcn,or morc.et:mdard proteins of known moI•cnlar v•gh't. (cec 4). The molecular wci^,hl and molccu6ar, radius of th: protein e computed with:955b.conSJcncc 1-mits;.. I the fr rd: t oin.hlph:t ren (1 and F,Ifor the sWndarJlprmcnr. Yra t': Y'a. andI R, valucs and (Uc .4.u„ed o'm:asurcJ mobihty of t5rt bullcr "'front!" (95) tkenct.chargc-.of Ilic pro4c cornputnl !Il):. 6)IOptrnLatian cf pore slzcFrum thc. Y,x„ )"o, and R:vaturs o' thc p rnecin and anyy one contaminnt, the optimal gel concentration iscomputed(10, 19, 15) 59). I6 the . Ferguson plots o6 the Protcin, and any onc contamimant arc . parallcl, then T,nt.= 0 and fraetiona- tion is carricd out in~z nonsiewinganti-convectant gcl, a.suerose gradient'.col- uni by isoclectric focvsing (see.8)'.or.. by, isotachophoresis (sce.9);. 7), Isolatiortn b'y, PAGE. The protein is iroGtcd byy prcparative PAGE in appa.ratusof'tlse desired loa&eapacity, using conditiTnss previoualyy optimized on , the analytical scale. 8) Fractionatioa by' IFPA: Using a vcry low geL eonecntration, or cn agarosc-polyncrylamide gel, one forms am~imallymech'anically, stable get vith t signuficant molecu4ar sievietg: (Sta¢kicg in a mulciptiuic buffer s)stem ecwn be used ass an operational'eriterion for ab:encee ofsignificant molecular sicving(or p,roteins:) A narrowrangeof'w ampholytc pl's ischoscn for b'est't reso.lulion. Moderate voltag:: g:adiint4(4D volt/em);ICad to temporary pattern stabillty andl aIdneara p~H', gradient'in 8 to 1I hours,.09C. Stability' of gradi- e,us mayy in some cases be improved in gls containingg sucrosc.. Conditions estc - I shcd for anal~tica1 IFPAarr ap- pliczbte. tot1iemilligram-prepacati+eo luvcll 9j Isotacbophoresis: Tfie pH,.ionic strength, tcmperature, and ge4 eonceo- tralion :vc sclected, usua)ly on t'te basis of Fcrguson plots. In addition; on: must >elcctIh¢ '•spacers": eithet syntheticarrrphol:tes witha broad distrtibutionof'n mobilltl.r, or prcferably'spm_ifie iom .
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96 with nYCbiditicss imtcrmcJiac betwcen th'e pro!c:o andiL4adjacent eontaml- nantp;). lsoeachopho esii:ean,be seaLd up to aeeommodate gram loadsrels tively' unlnRucnccd by 'g_I size. Suannmp Polyacryl0ntide gel elecktopholesu (f'AGE)) prov'idesavers:eilc, gentlc,., high reurlution rxthodior fractionatiom and plnysi¢al-chc:nital eharacterizaNorn of':molccules on thcb'asis of, siu,:com formation,.and'net~eharge The polyfn, eriL'1:7ion reaclion ••ln be' riSorous:y controlled to provide uniform gels of reproducible, measurable pore size over a wime'rao"a,This makes it possib'le to obtaVn rcprodueible rclative mobilrty (RJ)O vallucsa< ph'ysical'ch'cm;ical con- stants: Application and extension of Ogslon'i. (randorn fibcr) modcl for agcl: allows, for calc:ulatiom of molccular vulJlm¢,. sunfircc arca, or radiu•, frec mob:iliiy, afxl ivalcncce from R, .mcasurtc- rncrvat al scver I gel' conccntralions, to. calculalc gel concentration for optimal resolulion, and to predlet behavior of macrornolcculcson, gell gradientsby: coml(encrizcdl mtthod<: Extcnaonn of, clnv.icalmoving lioundaryy thcoryhlasIwcn ua d'.to Ecncrat, hiph'naic hnG fert systclm\ (pmviel.insg sclective stack-ing. unrtacking,.restacking; and prepan• ativc steady-stale-staeking).with kn~o+vm, opuating charactcriat:ics for anypH au 0n and 25eC: A generall strategp, forisolaiion of macromoleeuless andl for macrom)alccularmapping' h:asbeens d.a-vclopcd. Prcp,aratFve. scalc PAGE isopcrnllonai for, mllligram )oadss and'fcaaibla for grum quanlities:. Rrrlrenee. arM No@a 1. /.. Umar[in„ Anw. N.Y. Arml.' S<l: :tl,. l21 f 194/):. 3: 5.: Ra.n.•~d and L\V:irurasb, Se/r.at LV: ]11 119'39)'. ),: J. 5 ra+aru. anJ C:..1. O.: R. Mwru. SrP., J:~. 1 .9 (19b) 5. II Ar<h., n 1 D~iolrhY .TJ,~ [Id'~ 11 L:1 7 t:L'. E1 aaW~ T, M] , Ar,ul.~'. H lrrr.. 2] 19J f1969/. 6~f . 11 L, B h . J. R CI YbrcoZ, S 5"Rel ~ rtr.; , 173 /19611:. n J Af ~ B' H.1~. 26 C. A. wrW. i. J~~Urc! anJ L. Srwnra~ 163, t4a.11966~:.. f. A.: O.~ P[.cark and~ C. W..Dinpnan, Bio- rA.... .Y 1. r.(t 119Nx 9 A: E. DahOA. r. C. W. D'nfman. A C. rrac ~~ Jn/ JI }9 a%a). IOL n~. R wb rJ~ anJ: A. Chramla<A,: P.vr. hol. Arad S . ( . 63~ 9)O.f194V1 11 ,-- B~ <0 9~f19)t). I2. 1_ Sr J.C~ rr' 21~~ ITl (19f61: A.YCA bxn', H. V, Ar.+. n U . :{ IfT (I%]).: WvrR.. Aw4 Biaohrn: la„S 5 110 r. U.5~ Sral, J: Cl.w.. ~crnW Af Nr.~26, 8J5':(19.6): P. Cnna1..A_ Cnnarrraacn: D.: Rw : Dan.run,./. D:al.i Chrm_.,In Pr.esa 16..B1 J! DJrrt.w....N.Y: A[M..Sct. Ill:.ank I`lal. il /1 . AD m L. 5:. 3' M. 11 G .n £ V h L IC:!'S-l11 ,.FevY k1' If. R D e . and \~ A. TT . n. CA tr. 33 96 (1966). J R. Fl.~ anG R. Bnv..:. An.l. 4v,rnim 30.353 P. FI. B[canw„ J. \V,. Parr~ak'~ A. C. Pc.c«k„ Drn„Arr... OrepAra.Acro Ill. 139 IW69). I9 R_ Llm and E. 7aJJnon, Ana., /ernrhrm 7a, 9'(19)U1.. 30 A., Chramnx.:... unPrrbl.ihed da:J_ 21.. W. (:orman.. H. R. At.hlc<: T. E. HwRy, BoyA..r.1=6.1 ( 2_.R, A W:::nuerR,. U. Loen,na M. \ S: P[nman, Pru<. Aan AceJ, S[/; US~.ft, 1 it (1961 : 1 1 C k A F 5 d: J...P'.. T A crl . .3 .I 9 11966) 21.,D~1i.£1.<:•uehnrrr~: Nr.al.irrrr,9, Canalln- nal CarP.,. R«:.dk. A1d.,.AUr I%l, 24 _ lunRa}monJ,.Anw, N.Y. ArW. Srr. J31. 11. 96JA: 25. 1 F, Ar(yk• !,APRL PPJy~+r S/:1. YI] fl'MSi: H. r W L, D. 1 be c.E.. L u:.Mc~ .J. CArrn..f3, 01( ]6: CnrnrrcrrY eJ. A r.b..:Jr: Ar-.ican: CYana-1 mid Oe:, Pt:rochrmucah Drm. )0 Rxke/xlter Plu~ Nc~ York 395n. 3]: D- L'.. Sunvrrrn, 1.~. V; Malrel,i. Jr.., J. E Damell. Il.; Pror. .\'rn. AcW. Srr. VS' Sa„ 30°. HD65). 2e. T. G. Frrrn, R.. E. Ea,Ierlint. R. E. Buaa,. wB-hn.n. a. l]] flnMy_ 39; J. M.. Drr.,r. Sr..r.<r lu„23s Ju: R FnlaYarn ar,d. A' onramb+c4 wnM. D,n- rhn+.. 44. ]%: II9}II! }I, P. Daer[ amJ A:.CnnmFa[h..18id.; in Pmc. J2. /1.. R: ASaurnr, Onk-£LrkrmyrAn<.v Idr Gnrler. BC:Ln„ 19F9{,: tnnslatitin p. pr.ep- : A. H. Gordon, E rrro 4Phbrr,/r . r/ Pror~rnr /r. Porlf~rYla•w/dr GrU /IOPIIaW, y.ndon, I9f91.. ]l. Orsc El.rrru,^M1Orcrir Hnhlbrrra+hr. Canal, Irr .1 Cn•p^ Rock.:ak, Md. N. U.'E:. L«ninc:.B.rrAenr. l. 102, 251 (1%'i.. ,11. N..i:mc.purYanJr'. 1. Alaacn, Anul. B- [6rm. ]6, 14 flr;0). ]6 GL. Cl-ru' nd: B: 11: 7'm. Ibd.1), ] s u% J. )] G. A, 1)wer, G Olcr. G...P t.l..Arr C Jr 5. -. 11, ' 3<I95T).: lf CT i Tr.k Sh ' B, 1„ Sb1me. C: A Dluhrc, J. Pna.m. .[r/! 39 , 391 ~(19.rr4. ]9, E. M.. InWa+j anJ S:.RaYmPnd. Arrd:.Arn.. e.m..1), 26J fl%91: <J,Y: Y. Gal:maa. B.nth:udr. 39:. 996, O%11, 41. C. S. H:. Chee, J..fPiimrP s[LI . P.H w): 110] II%51:. 4' . 5. Hinen..S. Jrnradl,: A. TJsrll'.w An.J.. H!orAr.n. 21, 10( aJ..D. M: NO•rnr,. /t:. BrecAlr•r.BiuPfrac-Anc If( sao:ln661.. N. I! XArnk<m: AI. LcrY.P. sV[, And,.A.a- <A:.. ss. Jn. a%{r. JS h H. F . -J t.. O, 5. F rnter, h 116:.71 W. M. M' h 11 Bu,- , nb.ra, uT. n( -L R:.F.. Pr•rrwm ar•J E. E. DnJMU~~:,Anslr. CIJS. Ani~r~can Ch[m:cal: Sn[ry. ASy_„ Ch1<sr.r, 10.,, 1961', A: SJ:Yna. J. CArnrrrw..[•. )•%. ]J9 (1963). <6..J. 1'..C.a. na and .\I. Frie2man, 8i'orFrmisr.r. II S 66 (t~6J)'. J \S 1 T S A d.G' Arm 13. 121 (1%3) L 1 p.. FI P T b; A Hst, L`/d 30.2 l19 r/ ab 5 R d d N' N' Gm lu,.lb d: J, 23 II61 6J.'1 fI9N1. a A G..02.wn, f[cWalSer. 7rant:.51.:17N 99t).: ]C. - andC. F. Paeld;: DrxAc.n4rrJ ]l, a21:(1960). 31 J C G J'Ihp E' K n,. C. P. Rw•[I I MN M9 t J Ah.- C rm ]i 4397 (195n)- 1.. A r L 6e lr A .r.Ulo. Nr.miarrY.enJ A/Plr[rrl.n BbhJY; T 5\Ybrk d E. S.e:k',.F.tv(^IomA.HolranJ Ams.er-C %9: S. T: C L rtn :W 1. ]UIIanJrc, l. [nromw 1 , ):9. (194aF: 3) G3^Ack: i!. D:al CI .. SJ3; 12JT % 1. fa: A. A. Fc<cuun, r/.r..Aun:.r 1}!9<al 9wnl.. >'.T. G. L II<k- . yxJ A. POlrm, LaulrArw.. B" . 16s, a) (19M1' 3 J Ff :K. G. Kcnr~cE Aunrm IfJ,. I]N al%)).. 31. J. Alarlsc anu. K:,G.: K'rnn<k, Ani j%7 .. ~. 35. NT (19nd), G_ G. 5larrr, 16f('j(„AIn)Y'(I : G. 1. rm..e h xFer, M:, DIp(- tl Bir E (/on FFDJ(F[a 'T[at~ R:r,rAr S ) L.rr! 3 III It9w). sf w lnn anaE. AA hl D:erJu.,..Blaf~ Arrl 1fA IJ3 (19681: ~. 19'. D_ KbdbaeJ, G.. KapadiS A Caranbal~ Arid: Dr,:.l.r.r. {9; 1)S (19]1): 0aI. ~ ,^ P•am. for Pp<iml'tallnn: 9f T aIM la f Y f ft +. eaxr I mplw.cvc ~t .:~abl . ( A Aadbar(~ 60. A: G. i.<nnct: and. l: Atirfeli4 Anal, /14y [nrrn..JJ..3W (t91Ui 61. l,.U. Hrdnck' .nJ~ A l. Smilh...An[1F. rArm, B.u;h)"r.: 126, ISa (I%r):. 6.'. C- J: f): P. MorriLPav[14r Bb:' Pra. C 1 b9' Dvrn IJ. SJJ (1966) Q. G~ K. A 1 .- Ad.or., P.Prrn. CAerr_ 24 SQ`. , . 9TW : M..A. L. ShsPrm. anJ.l. V,.Maricl Ah9:.BY rAi.n_ 29;,505 ()%91; A. UtfL ~ A C11ra~" bach': D. RmJbar4 r6id- : M prn.. mmpratd'. protrama Isr IessLa9u+rr+ linean n,~:. / R• Pn bF F1.K aW M.\Y'. o]of Ar ifa6k u <cqueY rrem D AwlbarQ:~ ~ w. Rrrwlc ana O Tanfor4 !. Hwl. CJ:.IIii, S13..5161 (19)nl. ss. c'. wrbr. ar•dA[.fhbpna„!, a4q Su,.un6 u%9i. 66: P. Aw-c,.1/'b[h.rm, A%, 393~.(19U1. 61..P. F. Da•:on; Srian[r./U, 906 JY%Sk N. il. Dcrernsvan, Gr! Ctrnwdar~PpJ</(SRIM~ re V<rlae NrrYort 19nR)'_ w. E.. V. Chrc.rr rvf U. J. Le.h, E.AIJ rob[Y a5, J65 (1%9).: T0..1. C. G~JJ:n{., UY^emi[r91 Chrolw~kf•; trapbr. (D[k4r. Nd. Y'ank, 19651.. ' - 71.I J. LunncY. A Cbr.mbach, D. Rodla!lAnrl, . Brr.rnrm. Jf, ISt.119t1J -JI. 7i l. C. G,dJmar,.SrP- SN.: 3. 111 (19w} Ci. nF.on, Nnn,rc.IS), 19J:(I9WA. ]): Mj Canv, A. CAramb'=h! E NF9Mt B-•n. B:PN,r,, R:[. Co•n•r,nn. »,. 90/ 119]On: H, Krt>ae, U.' W'w+n:vut51:. Canllll C.. W. Hall.. E. F. Ntufrld; b/d: 42. aR (I911). M 11:. A' (iFR: A. RHJ[W. SL.WY[Y~- 1. )Arcari, Anall BrbArrn. lG, 150 (~IM74~~. 75; F.. G: ItrcnkNa, J. A Cnll„\V'. B. Gratati 1hm. n<s' H9631J D. RxrdSaN, unP "••u lifa:1 C tl I n rrlrl P. A'..AVmeaaitlilip < vl..a 1 . J1;. 31 (1969). 16: Al. w. Gom>ntY: K. Carl•m..l. RmrabR~ wnN..B•zArm.: ]5,..159 (19]0).. '6f ]l: B. K. Ilanoran arW s. Udenlniee41f3L.~.. FI (19A9). ~'. 7t..2. P: Bwri. IIM J, N. Aba»0. I" 21) u969/.."i A.'T, M, JP.ie, AfrrAedi E.m-L 21. ~ 19111. 80. R..AII Zacharirq T. E. 2e11,: ), tL.h:arllaq'. . J. 1.. wdeda«k w.d. BJPrh..r. M. 14 l%91. il A, Yanat. H.. Nafavav; 1'.,. F £ndurn.ro:..l.P1f,.M5 (196t1: U.l.li~ 6!. L . E.. V: OBee : EndanfrW. R5, 69U (f 9„C.. S. h dhi l. A. P K: P. F nJO. C. 4V ' hb 1.: Jr^ !.'~ Inal.: <S; ItlJ (1969). il. J.. E.. Walkrn enJ R: A. NillGr, Aard Mrrn. ]J, JS.J (1970):. U. A. Chrambac), Jb)d, If„5<J (1966F !.Jwr.w 1 1 3. 6.18 (I9w3 A- Leui+Fla~ M: W.F' BI C/ CAiw. A[ft 9 II%I 95. P K. k \V B'dw A. Ohnrrba4'j Chn-.E d -, Afra6 33. 7.10 (I9111 IF B. Af- C V Ai.,ln 1 MPL BKark. Jah 40. 1 96 1: B. AIPa e.id N.P. !. , V6er. 3. , IU16.(1%f): ~•E~ A~Hirvlrmn, h'errrn 214. 703 119i1k ~a.. D: K I, dR: A Re a( Id. Prac rs.f.3 05 ft.I J0.(I%]).. +~.. [t. C. Fa b k. J C. ~ inrhal R-.[L Br.GmcAr. DIopA,r Rrr CD•r R19J (I 63 D. Nxh 4 .. EF V Shim rNar, Aj. K Sr/ ..5. b6 w t 663:: R. L+0. J• } 91Janc. G.A, D e:f,..Anal.. D1PMta /39691' tv.B. /•Ima anJ V. MIntram, l•x.~~n Srl ('_1':.5:. %T II9r.11: d 71/t~ IIc9r.tC.,. 1, Fr^r[in. A+ar.' Drash.d ff.~ 90..D! F. C- and R. E: Pilner, A.aJr a/df 23;, u Uv6a1.
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97 9(. If': !'. Anker, FERS' (Frd, E.r, CYrMen.. 393 (191r11. Hrbrhrnr, 15:,l6/nal 1~ G«sscl enJ1: WWOwr).ili, ibld.. : 152'(1959): H C B-rnbam, ID•dSJ 553 I9 91 D..GuI 41 . HW. S r9e (19AV1 i 9t. J. Y 6taluN, 1 5 rrcr151, 99e(1966). 11 93 1 P . Ir. R. A'..I ti.1rN.'. P: F. Hrrvclt . H I\ asibcE. L F.. VMIYeI. P. L'. -:n,!'rvc. Aur. AaW.' Sri. V.S. 5.; 7=3 YIr.61Y 91 -i. N..lorin, in nrtlaratlon:-. M_ L R.urrr. . CM1rameacF, Alvlriyhvl~ D.~rr ,u Oory~, 1 ~'alranal. Trcty.-al I INJr:na-' n, $rn1-,. SMintfirlJ. VaTI51, 1'1)0).: rl'B 196M5 ra I9W91. Y,. FnAlbrelf~ l. Ar,rrr., Ctrrm. Sar: 11.' -A1i (1950)r 91. T. S-in, A. CnrambxM1, M,: A. Na9yNOy Awal.' 11i.uh}wr, 9, )11 (1963). 91 .U. Dr„vn r, (ALL3I'23(1169).. 99.B B. Sa a ane Pr /( H man~, 81a. Arwr. J.. 1., 131 (1966)- X: 5 ,nf .nJ A. G. B BUrhr+r D h A/n111 ~]9.(19611. D B 5nrna ~JP,.Rarbnam, /: 8wr. CA Sal, 71M9 ((961),.R'. A. Rr/... Lrld, l. R. Inmaa R(: Miar„E A~P~IIi, H~w'hii./ r.y T; 13 11968,: Il. J. l<+u, C' V. Cf•cr.r.. B: 4a•q, Aw.l: 8nrhrm, 33! 16]'(1Y6L1-i V:. A6~Ix•aaM! Snan,l. J. Clur, Lub, ln,rrr..ll. 59 lIY6i1:'L/. l. Gcutd,:. J' C..PinJS H.,R. Ma.rhsr.,.A.ll. GorJun; AnaL,H;o h. m: 39, 1(196N/. IOD. 5.R,mnnE ani•1 &. Sl~ lord~n,SrOSre,, 1, 99/19M5.. IDIL. $rra~rR,FrorrJei Dwf. F/u/Ai CaLbp. Druiel IS, S)1:119611: U..A..N»•, It M. Tmiil..ll:P. RaPPiycrl A..LH/ox4.w SL,' 1_I'119h91.. 10_: A. U. - d'AFes and 1 i Pi. SaAeL'' 0,2. Sx' Cbl ..D)o1 ~V, IFl1 (1961).. IDl.: II. HArW, Sri: T L LT.('.1191D9.. 10/. G O J A: L L.a efLa rl196m, M1 ( Y6l/' J,.S:.F - lEh.T IFrd. Er: 8f.o h n-Srrra Lr a LI ('M "I)„FL lss !a[t aaO:A. C R' 8 n<Jrea -ihFr.: Rr . Canmiur. 72 ,ti (1961):.R.. F. RHty a.rd M. 1:. Cukman, J..1ab.CLn, Afrd: 73; lli (194F1:.C. W..WriL%e, J: CMrmqaal.. J[, )6_ ((068/: M. H'. I/aYCa arrd D. Wcllnrr, J. D.vI..CMni. 13i,;66)6'(1969;;.1:. C1!aiT Pwas, Sr~. S~t.'S, 5l1 (t`i10);. 1rH. R: Fra,er; Anal OnoMrwr_ 7l,.576(IT01. 106.R.: D. Mafl-l-i C. N. /aplan, .ti.CLrpn. -n; J. Chw.. f-n.. MrrcA' " IDI, Z L ArJS4 St, - TWL 16, ~' r(1969). 5~
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98 Statement of H. Russell Fisher, M.D., Pathologist, Glenddle, Calif. I am H. Russell Fisher; TLD., living in Glendale, California, and a pathologist certified in Anatomic and Clinical Pathology with a special interest in the study of tumors. 1 am Emeritus Professor of Pathology at the University of Southern California, a past Vice- President of the College of American Pathologists and a member of the Americ.an Medical Association, the California Medical Association and the Los Angeles County Medical Association. I am a former Delegate to the House of Delegates of the American Medical Associa- tion, which is the policy malang body of the national organization, as well as a former member for many years of the Council of the Los Angeles County Medical Association, which is the policy making body of that organization. Currently, I am the representative from , North America:on the Executive Committee of the International Council; of S,-)cieties of Pathology. As a recent delegate to,the American Ledical Association and former Councilor of the Los Angeles County Medical Association, I have a special interest in the decisions made by organized medical societies on matters of the public health ~ and have been deel?ly eonccrned that such d'ecisions can be emotionallqV motivated vrithout a sharp awareness of scientific responsibility and.., accountability. Actions by the House of Delegates of the American Medical Association frequently originate at the local leve3,, the county medical society. and because the same individuals who are infliuentia :'rom, tt I 1
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99 -2- at the local level are frequently representatives in the state r..zdical associations and in the American Medical Association, it is understandable that policy opinion can and usually does sweep from the local LeveL to the state society and then to the national crganization. 3imce the policy adopted by the House of Delegates:is often made by the same few people responsible for policy decisions at the local and state Levels, it is even, more ~mportant that policy at the local level be based on, scientific facts, not emotional pre- lndice. A recent example where this was not the case, was the action c° the Los Angeles Cour.ty Medical Association, (LACN.AY, the largest l3ca1 association in the country, on the issue of so-called passive or public smoking. The fundamental point here is that there is no sc:entific proof that inhalation in an atmosphere in which there is cigarette sr..oking presents a hazard to the health of nonsmokers. '- tase ay opinion on m•,v review, of the scientific literature, as well a; the statements and public positions of scientists who are both ;:ro and eon on the smokin~; and health controversy. Notwithstanding the scientific facts, LACt1& is officially sup- k:rting the California Clean Indoor Air Dnitiative G.h2ch, is scheduled to be on the California ballot this coming NoNember. This action f'~llows the recommendation of the association's Committee on =n*ironmental Polilution (1) to restrict smoking in LACMA's headquarters, 1
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100 -s- and (2) to undertake a so-called public edueation program about the a1'leged hazards of smoking for nonsmokeY-s. In making its recommendations, the Committee ignored'the basic its own invited specialistt in this field, Dr. Ralph C. Jung, Associ- smoke is harmful to nonsmokers. It even ignored the statements of fact that there is no scientific proof that atmospheric tobacco ate Professor of Public Health at the University of Southern Ca1i- fornia. Because I am not a member of the Committee on Eirnironmental Pollution, I di'dinot attend its meetings. However, the milnutes of the Committee, which I have examined, indicate that on January 25, 1978, Dr. Jung presented a paper to the Committee entitled "Pollution in the Interior Environment -- the Data Base," which is frequently the jargon for a paper about tobacco smoke inithe atmosphere. During a question and answer period that foLlowedithis paper, Dr. Jung stated "that there are no good data regarding health hazards among adult passive smokers." (Quoted'from minutes.), From a{y review of the scientific literature on this topic, as ~ well as from my, review of the minutes of the January 25 Committee meeting, I know that the experi~ments in this field are numerous. Many have beeniconducted i'n unrealistic circumstances that have little or no counterpart in usual or even extreme living conditions. To discuss all of these studies at length -- or even all of the experiments rel, Din` Accc -tuc aubi WeL" mea; usec souJ --mo} '.hai seal not real of C of ; .ion '_eve t
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ruri'ng ILs ee a± -4- related by Dr. Jung at the January 25 m=_eting,(as note&in the minutes), - would abuse the average read'er''s tolerance for detail. Accordingly, I will limit my discussion to only several of the studies mentioned by Dr. Jung. One study referred to ursealistic concentrations of carbon monoxide (CO) produced byy assiduous smoking for an hour in a 15 cubic meter room. Carbon monoxide is one product of smoking - as well as a byproduct of other types of combustion - that can be measured accurately in the air and in the blood. Hence, it is often used as an index of atmospheric tobacco smoke even tuough~other sources of carbon monoxide, wYLich are frequently more important than snoking, should be considered. It should be noted that the room that Dr. Jung was talking about was about 8 by•6 by 10 feet and was sealed. Such a room is smaller than many bathrooms and is cert'ainly not much of an office for people to conduct business. W'hat Dr. Jung failed to mention was a study performed under realistic conditions in whdch 49 business offices and 293 employees lnclud2ng 122 smokers were studied with air and blood determinations of C0: Rooms in which only nonsmokers worked had a concentration cf 2.59 pom of carbon monoxide and rooms with, smokers had concentra- ~'-azs up to 2.78 ppm. These concentrations are far below the 50 ppm :eveliset by the U. S. 0ceupational Safety andi Health Administration ns the limit for industrial eaTosure over an 8-hour period. More
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102 -5- revealing, the CC in the 3lood of nonsmokers exposed to atmospheric tobacco smoke was less at the end of the day than it ras when they came to work in the morning, due perhaps either to diurnal variations or traffiic:fluctat'ions. Dr. Jung also referredito studies in which concentrations of 30 ppm!were developed. Again, these studies were conducted under extreme condition s such as 2 people smoking 10 cigarettes in~an hour in an unventilated automobile and groups smoking'as much as they could in a sealed room. In contrast to these unrealistic conditions, Dr. Jung noted that a study on airplanes showed that with 50% of the passengers smoking, the CO concentration did not exceed 5 ppm. In light of these studies, there is little wonder that Dr. 3ung was unablie to point to any health hazard-to nonsmokers. Despite the statement of Its own specialist, the CommittQe concluded - without any additional evidence noted in the minutes - that "the data which has been presented this evening by Dr. Ralph C. Jung furnishes additional positive support'for what appears to be irre- futable evidence that smoking,iu detrimental to . . . nonsmokers (passive smokers) who are required unavoidably to breathe the smoke which is produced by active smokers." The regrettable feetsre of this is that, in the absence of ary scientific proof of harmifrom atmospheric tobacco smoke,, we are dealing with a social question and not a medical one. In this re- gard it should be noted'that, since fears and phobias can lead to ti Me c7 ti tY at tr
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P. 103 ill health, those who urge policies based on fear and not scien- tific facts could be making a medical problem out of a social one. ihis is indeed a strange prospect to see coming from the efforts of members of the medical profession. Smoking can be annoying to non-smokers, particularly in crowd'ed areas such as elevators, :~here smoking is rude and objec- tionable. But rudeness is hardly a topic for legislation, any more than garlic breath an& armpit odor, bot'h of which can be objection- able to smoker and non-smoker ali%e. Smolfing,has been an accepted custom since the founding of this count'ry. Medical societies, in officially supporting the Clean Indoor Air Initiative, are lending their influence and prestige to restriet' an established social custom •r,zt~r no scientific medical ;ustification.
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104 HARVARD UNIVERSITY . (6t7) a3r3F9 (6z7)495-" STATEMENT'OF DR. CARL C. SELTZER r sA I am Dr. Carl C. Seltzer, Honorary Research Associate at.the. :...: s Peabody Huseum„ Harvard University. I'vas formerly Senior ResearchAssociste at the Harvard University School of Pub1icHealth. My work . in the smoking and health area is extensive and I have published over ~ thirty (30) articles since 1964 on the subject, many dealing with the 1 relationship between smoking and:coronary heart disease. I was a consultant to the Surgeon General'sAdvisory Committee onSmokingand Health aa+~ (contributed a sectiont'a the 1964 Report) and am presently a Fellov of the Council', on, Epidemiology of the American Heart Association, lfy, investigative work in the heart disease field includes participation in studies involving 1" the Framingham Heart Study, the Veterans Administration and the %aiser-Permanente ;, Foundation. . „ In my studies of heart disease and smoking, I have found it necessary to consider a great deal of scientific literature in the smoking and health area. Most recently, I have reviewed information on the claim that the exposure of a person to environmental tobacco smoke represents a aerioushealth hazard. As an experienced investigator, I must say that most of the evidencee on vhich~this~ charge is based consi'sts of experiments which do not approximate real-life situations. Pzw.onr Mvszav tt @rocwnrr Ave- G'nYelIDC" MASL+IX.SETR.OSf38, tJ$.A.
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il ':1 neate to f a this 105 =2- Kany of the claims about ambient tobacco smoke have focused on individual conatituents.Carbon monoxide from tobacco smoke, for example, is often singledout' asthe greatest threat to non-smokers. A recent revievof the ciaimed hazards of environmental carbon monoxide generated by the burning of cigarettes has been publi'shed:by Wakeham in PREVENTIVE ?O DICIHE, a )ournalof the American~Health Foundation edited by. Dr. E.L. Wynder (1). In this overview, Siakehamconsiders the sources of carbon,monoxide, the concentrations of carbon monoxide in enclosedspaces,.the amount inhaled, the observed carboxyhemoglobin (COHb) concentrations and the response of healthy individuals to increased COHb levels.. Wakeham,points out that while there is a large amount of natural carbon monoxide in the earth's atmosphere, attention is generally given to~man-made sources, including smoking in "enclosed spaces such as ronme, buses, automobiles, airplanes, arenas, etc."' Pointing out that the AzierdcanConference of Governmental Industrial Hygieni'stshas established a threshold limit of 50 ppm (parts per million) as the maximum for daily 8-hour exposure (2)', Wakeham cites studies that show it is impossible to attain this concentration of carbon monoxide in a closed room. Due to ventilation, there appears to be an upper limit to the possible build-up of carbon monoxide concentration from smoking "in the real~lifesituation." Since themain.effect of absorbing carbon monoxide is the formation of carboxyhemoglobin in the blood, the levels of COHb are important. The YH0 has suggested a maximum of4Zearboxy.hemoglobin level to be safe from all Possible adverse effects from continuous exposure contitions (3).. 2-
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106 Non-smokers will generally, have less than 2% COHb levels and this level will depend on several factors such as type of occupation~ location of work and residence, etc. There is no convincing evidence that carbon monoxide from tobacco smoke is a health hazard to non-smokers. Nicotine from tobacco smoke is also claimed to have harmfulieffects on non-smokers. This elaim, must be viewed as unproven when one.considers that the 1964.geport to the Surgeon General stated that, as to smokers, nicotlne. "probably does not represent a significant health problem." (4); Moreover, when two Harvard scientists tested for tobacco smoke in public places by measuring nicotine, they eatimated that a non-smoker absorbs from 1/100 to 1/1000 of a cigarette per hour.. (5). With regard to the claim that the children of parents who smoke are adversely affected, I have revieveda number of reports. The eleim is contradicted by Yale University investigators who studied families in three USA towns (b)~. These researcher~s,after studying respiratory symptoms, disease, and: lung functiono concluded that "parental smoking had no effect on children's symptoms aad lung function."' It is interesting to note the position of the U.S. Public Health Service on the subject of environmental tobacco smoke as stated in their 1975 report to Congress (7). Chapter 4 of the report reviews recent findings in this area and concludes that theeffecta of cigarette smoke on healthy non-smokers consist mainly of minor eye and throat irritation. It does not elaimm that environmental smoke is a health hazard but.states onlyy that people with certain heart and lung diseases--sick.people--max suffer ^exacerbations of their symptoms" as a result of exposure to
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107 tobacco smoke-filled environments. This certainly does not support the extravagant health hazard claims of those persons who demand highly restrictive legialation,vith respect to smoking. The persistent demands of those in favor of restrictive legislation is in complete variance with the stated views of many scientists whose ar.ti-smoker views are well-known. Dr. Ernst L. Wynder, President and Nedical Director of the American Health Foundation has stated: "Passive smoking can make the eyes tear and eanbe otherwise unpleasant, but it'has no influenceonhealtb. In thi's case the doses are too small." (8) Dr. Jonathan Rhoads, Chairman of the National Cancer Advlsory.Board and a past President of the American Cancer Society in a discussion of smoking and health has said: "I do not have hard evidence in that •ii'reetion (that there is a harmful effect from smoke on the non-smoker). To my knowledge, it is not, in fact, actually harmful." (9) Finalily, Dr. E. Cuyler Hammond, Vice-President, Epidemiology and StatisticallResearch, of the American Cancer Society, stated that there was "no shred of evidence" that a non-smoker can get cancer from "second-hand" smoke and'"there is a lot of evidence that he cannot." (10)' In my opinions there is no scientific iasis for concluding public or so-called "passive" smoking is a health hazard to the non-smoker. Hence, fovernmental action to restrict smoking must be considered unwarranted under these.circumstances. 6-
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1. Wakeham, H. R, R., Envi'ronmental Cerbon~Moroxide from Cigarette _ Smoking - A Critique. Preventive Medicine 6, 526-534, 1977 2. Threshold Limit Values ForChemSeal Substances 1nWorkroom Air, in "American Conference of Covernmental Hygienihts," , Cited in Med, Bull. Exxon Corv, Affil. 36:136-171, 1976 3. World Health Organization, "Air Quality Criteria and Cuidee For Urban Air Pollutants." TechnicaL Reeort Series, 506, 1972' 4.. U.S. Department of Health, Education and Welfare, Smoking and Health, Report of the Advisory Co®aittee to the Surgeon General of the Public Health Service, Public Health Service Publication No6 1103, 1964 5. Hinds, W. C. and M. W, First, "Concentrations of Nicotine and Tobacco Smoke in Public Places," N,E,J.M. 292:844-45, Aprili 17, 1975 6. Schilling, R;S.F,,, Letai, A. D., Hui, S. L., Beck, G. J., Schoenberg, J. B, and Bouhuys, A., Lung Function, Respiratory Disease and Smoking in Families. Am. J. Epid. 106:274-283, 1977 7. The Health Conseauences of Smokinz, 1975.. U.S. Department~ of Health, Education, and Welfare. Public Health Service. . Center for Disease Control, Atlanta, Ga. 1975 8. Wjnder, A.L., Citedin.'"Schr+eizerIlluatrierte" October 25, 1976. 9. Rhoads, J6, Interview on station WTAF-TY, Philadelphia July 16, 1975. 10. Haomond, E,C „ Summary Proceedings of the International Conference on Pub1leEducationAbout Cancer. UICC Technical Report Seri'ea,. 18;13, 1974. j
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109 CURRICULUM:VITAE 4 ACADEMICTRAININC Datea June1929 Febrvary. 1933 POSITIONS AELD Dates 1931-1935 1936-1956 1937-1938 1837-1942' 1938-1941 1938-1942 1942-1947 1940-19501942=1946 1929•present 1942-1976 3 4-,21 0'- 7 8- 8 Carl Coleman Seltzer Institution Harvard University Harvard University Position Research Pe11ov Biological Science Anthropologist Research Assistant Fatigue Laboratory, Consultant Anthropologist Research Associate. Anthropology Research Associate Physical Anthropology. Anthropologist to Grant Study Consultant Anthropologist Associate Editorliember Research Fellor inPfiysicaL Anthropolcgy Degree A. 3. Ph. D. Institution Harvard University Harvard Uhiversity Harvard Ufliversity Office of Indian Af~fiira U.S. Department of the Interior 9arvard UnlversltySarvard'IIniversitg Harvard University Department of 9ygiene Robert B. BrlgAam Hospital Boston, Massachusetts American Journal of Pbysical'Anthropology American Associatiao of PhysicallAnthropology Peabody.Museu. Harvard University 0
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110 Dr. Carl C. Seltzer 1950-1964. 1957-1971 1963-1968 Dec.1964-present 1965-1975 1968-1976 1976-present Board of Free}maa Research Associate iesearch~.Ahsociate Physical Anthropology Fellou, Council of Epidemiology, Consultant Senior ResearchAseociate in Biological Anthropology Page 2 Harv.ardUniversity Adolescent Unit Children's Hospitsl Boaton,Massachusetts Department of Nutrition Harvard: Sehool'of Public Bealth American.Heart Aasoeiation Veterans Adminiatration, Boston Dutpatdent Clinic Department.of Nutrition Harvard Bcbnoid6Public Health Honorary Research Associate Peabody Huseum, HarvardUniversity
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111 BIBLIOGRAP1iY Page 3 "Physical Characteri'atics of the Yaqui Indians", Texas 2echnolo_gical _C_o}lege- Bulletin~ Vol.7CII, No.. 1, January., 1936 ° , "A Critique of the Coefficient of Racial Likeness", Ati.. J. Phys. Anthropology, 23cJuly-Sept., 193A,.p..101 "ihe Anthropometry.of the Western and Copper.Esifimos, Based on Data of Vilhjalmur Stefansson", &mman BSo L,5:Sept. 1933, p.,313 "The Jew - His Racial Status"',. - "An Anthropological Appraisal",Narvard Medical' Alumni Bulletin, dpri11939', p.1 'The Racial Characteristics of Syrians and:A'rmeniana", Papers of the Peabody Museum of American Archeology and Ethnology. Harvard University, XLI, 1936~ 77 "Contributions to the Racial Anrhropologyy of the NearEast"', Papers of the Peabody.Museum, XVI, 1940, 39. "The 'Masculine' Component and Physical Fitness", Am. J. of PhysicalAnthropology.,N.S. 1:. March 1943, p..95 "Anthropometry, and Arthritis: I. Differences betveenRheumatoid and Degenerative Joint Diseasee: Maiea"' Medicine,22,22: May 1943, p. 163' II. Differences BetveenAheumatoid and.Degenerative Joint Diseases:. Females, Medicine 22: May 1943, 189. . "The Value o.fthe Shoulder-Hip Ratio as an Index of Masculinity and its Relation to Dynamic Physical Fitness". Revue Canadienne deBiologie, 2:Auguat, 1943, 329. "Selection of Officer Candidates"', Harvard University Pre..s,.1943 "Anthroyometric Characteristics and PhysicalFitness"', Research Quarterly, March 1946. "Racial Prehistory inthe.SouthvesC and the Naeikuh~Zunis", Papers of the Peabody,Nuseum.,.XIQII, 1944, 33 'The Relationship Between the Masculine Component and Personality", American J1 Phys..Anthropotogy, N.S. 3:March 1945, p..33 0 0
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112 Page 4 '"Bodjr Disprop,ortions and'Dominant Personality 7raits", Phychomatie Medicine, VIII, March-April 1946, p. 75 "Somatotypea of an Adolescent Group'",.Am" Jl Phys_.Anthropology, Y.S. 4::June 1946, 153 "AcademitSuccess in Colllege.and Public and Private School Students; Freshman. Year at harvard", The Journal of Psychology, 25:1948, p. 419 "Phenotype Patterns of Racial Reference and Outstanding Personality 2raits"', J. GenetitPaychology, 72:1948, p. 221 "A Comparative Study of the Morphological Characteristics of Deliquents and Non-Deliquents",DnraveLing Juvenile DeLiqueney.,,Glueck and Clueok, 1950 "A Relationship, Between Sheldonian Somatotype and Psycliotype", J.P.rsonaldty,. 16:1948 "Constitutional Aspects of Juvenile Deliquency"„ 0o1d~Spring Narbor Symposia on Quantitative Biology, XV: 1951, 361 "Body Disproportions and Personality Ratings in a Group of Adolescent Males", Crovth, XXIII, 1959, p.1 "RSaturitygatings and the Prediction ofNeight of Short 14-year o1dBoys'",. Pediatrice„ 1961 (Gallagher, goswelQ, and Seltzer) "Skeletal Age, ChronologitaliAge and Maturity Ratings in a Group of Adolescents°, 196:1i (Gallagher, gosvell and!Seltzer). "Masculinity and:Smoking'°, Science, 130.:No. 3390, 1959, .p. 1706 "Some Narvard Men and the Smoking Habit", Narvard Alumni Bulletin,.Pebruary.4, 1961, "Why People Smoke", Atlantic Monthly.,,July, 1962"4forpjological Conatitution and Smoking", J.Am. MedicalAssoc.,183:639-645, 1963 "'Changes in Specific Gravity and aody Pat in Overveight Female Adolescent as a Result of Weight geduetion", Ann..N:Y,. Acad. Sci.110;913 „ 1963' (Coldman, Sullen and SeltzerY
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113 Dr. Carl C. Seltzer Page 5 "Satw" Iron ,{nd TFon-BlndingCapacity in.Adolescents. I. Standard Values", Am, J. Clin. Nutr. 13:343, 1963,. (Seltzer, Wenzel and Mayer). "SerumIron and Iron-Binding Capacity in Adolescents. II. Comparison~of.Obese andNon-Obese.SubJects", Am. J. Clin, Nutr. 13:3 Y., 1963, (Se.ltzerand Mayer). "bccupation and Smoking inCollege Graduates", J.. App1. Psychol. 1r8:1-6„ 1964 "!iorphc.lbgieal Constitutbon of Smokers", Special Report prepared by the Surgeon General's Advisory.Committee on Smoking and Health. O.S. Dept. Bealth, Educ. and Welfare. Public Bealth. Service Publication No. 1103, 1964 "'Body,Build and Obesity - Who.are the Obese'". J.A'.M,A'., 189', 677, 1964, (Seltzer andMayer). 'The Triceps Skinfold.al a Predictive Measure of Body, Densityy and Body Pat in Obese Adolescent Girls".. Pediatrics, 36:212-218, 1965, (Seltzer, Goldman and Mayer). "Constitutional Aspects ofSmoking and Lung Cancar^. "Psychosomatic Aspects of Neoplastic Disease". Pittman MeditalPublishing Co.,Ltd. 1964. (ihe. Proceedings of the Third International Conference of tbe. International, Psychosomatic CancerStvdyCroup held at NevnhammCollege, Cambridge, England.)') pp. 13g"151 "S'tandards.of Obesity".Seetdon for Obesity Manuali. Ditision of ChronicDiyeases, Bureau of State Sirvites, O:S. Public Health Service, Washington, D.C.(1965). "Hunger and Satiety.Sensationa in,Men,Women, boys and Girls: APreliminary. Report." Annals ofth'e Mev York Academy of Sciences. (Monello,Seltzer and Mayer), 131:593, 1965 "A Beviev of Genetic and Constitutional Paetors in Bman Obesity.."' Annals of, the Nev York.Acad..Sci:., 134:688-6951 1966 "Hungesand.Satiety.Sensations in Man". Postgraduate.Medicine, 37, A-96-100, 1965(Mayer, 23onelloand Seltser) "A Simple Criterion of Obesity Based on Triceps Skinfold Thickness", Postgraduate Medicine, 38:A-101-107y 1965 (Seltzer and Mayer)
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114 Page 6 Dr. Carl'C: Seltzer "Dimitations ofHeight-Weight Standards", NevEng. J. Ned.,.272:1132y 1965, "Appraisal of Nutrition" (Editorial)., The Nev Eng.,J. Ned.., 272:1129', 1965. "Some Re-evaluations of.Build and gloodPressure Study.,1959- Posderal Index, Somatotype, and Mortality," New Eng.J. Med., 274:254-259, 1966, "Constitution and Heredity in Relation to.Tobacco Smoking", Aan. N.Y. Acad.. Science, 142:322-330, 1967. "Standards of Obeeity'% Section for 06esity Manual, Division of Chronic Diseases, Bureau of State Services, U.S. Public Health Service, Puti. Health Service Publication No. 1464, 196'6 "Tobacco"'Smoke as a Possiblh Mutagen Affecting the II-Chromosome: Parental Smoking and Sex of Children", Am.J. Epidemiology E3:530-536, 1966 "Hov Representative Are the Weights of Insured Menn and Womenl:,. JAMA 291:221~224, 1967 "Body.Measurements in Relation to Disease", Part I'and Part II.Postgraduate Medicine 40:A107-A11l, A145-1151 "Genetic and Anthropological Factora in Obesity"',.Modern Treatment,.pp. 16-30, Vol. 4, No.6,.Hoebner6 Co. 1967 "Greater.EelSability.of the Triceps Skinfold over the SubaeapularSkinfold as an Index of Obesity", Am. J. Clinical Nutrition. 20:950-953, 1967. "An Evaluation of the Effect ofSSwking on Coronary Heart Disease@, JAMA 203:193-200~ 1968 "?torphological Constitution and Smoking. A PurtherValidation"„ Archives of Environmental Health, 17:143-147, 1968 "Genetics and Obesity", In Physiopathology ofAdipose. Tissue. Edited by J..Vague. Ewcerp.ta Nedica Foundation,.Amsterdam 1969, pp. 325-334. "Thromboembolic Disorders and Oral Contracep:tivea.- An Editorial oievpoint:, JAMA 207:1152'(geb 10). 1969. Dr. "Ove "Bod 'Cig "Cri "Age "Ant; . "S, "Dif "Adolescent At2itudes Toward Wei8 ht and Appearance'",(Dwyer, Peldoan, Seltzer and Mayer) J..Nutritional Education 1:14-19, 1969"
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115 Dr. Car1C..Seltzer Page 7 "Overweight and Oresity- The lssociatedCardiovaseular Risk"', Minnesota Medie.ine 52:1265-1270„ (Aug.) 1969. "Sodj. Build (Somatotype) Distinctiveness in Obese Yomen", J. Am. Dietetic Aas. 55:454-458 (Nov) 1969 "The Effect of'Cigarette Smoking on Coronary.Beart Disease - Where Do We Nov Stand7^, Arch. Environmental Kealth~ 20:418-423, 1970 "AO Effective Veight-Control Programia a Public School System", Ae. J..Pub. Hlth. 60:679-689, 1970 "Belieb'ility of Relative Body,Deight as a.Criterion of Obesity"', Am. J.EpidL 92:339-350, 1970 "Cigarettes and Heart Disease", N.E. J. tledL (letter),284:557-558„ 1971 "Twin Registrie in the Study.of Chronic Dieease", Report of an International Symposium i-SanJuan, Puertoflico, 1-4December 1969. Aota.Med. ScandinavianSupplementum 523 "Critical Appraisal of the Royal College of Physicians' Report on Smoking and Health", The Lancet., January 29, 1972, pp. 243-248 "Smoking and Nealth", The Lancet, Narch 11, 1972, pp. g86-588 "Age and Physique in Healthy White Veterans t aoston", (Damon, Seltzer, Stoudt, and Bell)., J..of Gerontology27':202.208, Y972 "Antrropometryin,the Notmative.Aging Study.of Veterans:: Physique and Age, Serism Cholesterol, Urie.Aci'd, and: Personality"', (Damon and Seltzer) Aging and Biman Development, 3:71-76, 1972 . eSmoking Among White, Black and Yellow Men and Women", (Priedman, Seltzer, Siegelaub. Feldman and Co11en), A.. Js Epid.96:23-35, 1972 "Differences Betueen Cigar.and Pipe Smokers in Healthy White Veterans", Areh. Environ. Health 25:187-191, 1972 "Smoking Sabits andtheLeukoeyte Count" (Priedman.,,Siegelaub, Seltzer,Peldman, Co1!len), Archives of Envizonmental Health, 26:137-143, 1973. 0
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116 Dr. Carl O. Seltzer Page 8 "Obesity.:. Bov it is.Measured, What Causes It, Bov to Treat It"' (Seltzer and Stare) Medical Insight, 5:10-22, 1973 "Nail Survey.IIesponse by.Health Status of Smokers, Nonsmokers, andEz-Saakers". (Oakes, Friedman, Seltzer),Aa. J..Epidemiology.(98:50-55, 1973)~ "Cigarette Saoking and'Exposure to Occupational $azarda. (Triedmman, Siegelaub, Seltzer) A',.J.,Epidemiology.98.:175-1g3,1973 "Relationship Betveen Emotional Stability and Phystque". JARfA 226.:86-87, 1973"More an Sznking and Heart Disease". Nev England J. Med. 289:1200-1201, 1973 "Cigarettes, Alcohol,.Coffee and Peptic Ulcer" (Friedman, Siegelaub'+ Seltzer)'. Nev Eag. J. Med. 290:469-473, 1974 "Cigarette Smokingand Longevity in the Elderly" Medical Counterpoint, 6:29-33, 1974 "Smoking and Drug Consumption in White, B1ack,and Oriental Men and Siosen (Seltzer, Priedman,Siegelaub)Am. J. Public.HealtS, 64:466-473, 1974 "Smoking and Canoer"'. Nev Scientist (letter). 62:195-196,1974 "Effect of Smoking on.Blood: Pressure"' American &eartJournal 87:558-564, 1974' "Bacial Differences in Serum.and Urine Glucose after Glucose Challegge".Diebetes 23:327-332, 1974 ((Dales, SYegelaub, Feldman,Frledman, Seltzer, Collen) "Smoking, Weight Change, and Age" (Carvey, Besse, Seltzer) Archives of Environmental Health, . 28:327-329; 1974. , "Heaffihg Loss inAdults" (Siegelaub, Friedman, Adour, Seltzer) Archives efEnvironmental Health 29:107-109.,,1974. . "Smoking Habits and Pain,Solerance" (Seltzer, Friedman, Siegelaub, Collen). Archives of Env.ironment'a18ealth„ 29:170-172y 1974 • "Cigarette Ssoking and Serum Chesiatry. lests" (Dalu , Friedman, Siegelaubj Seltzer). J. Chronic Diseases 27:293-307, 1974 Dr. Beal • "Eff . "S1 "Seo '7iai "Sco "Smo "Sto "Cha "S to
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117 a a ® Dr. Carl C. Seltzar Page 9 8ealtti Service Dtilization by Smokers and Nonsmokers"' MedicalCare 12:958-966, 1974 •'Zffscta of Selection on Mortality" (Seltzer. Jablon). Am..J. Epidemiology.100;367-372,1!I "Smoking and Cardiovascular Disease" AuericanHeart Journal90.:125-126, 1975"Ssoking and Cardiovascular Disease in the Elderly" An, Js Medical Sciences 269:309-315.,,1975 "Kail Survey RespousebySmoklog Status"(Seltzery Eosse,.Carvey) Aa..J. Epidemiology 100:453-457, 1975 "mokin:; and Heart Diseue" Ths:Lancet, April 3, 1976,.p. 741 "Smoking and Coronyry Nsart-Disease" The Dancet, June 19, 1976, p. 1351!-2.. "Stopping Smoking and G.H.D." The Lanoet„ February 19, 1977,.p. 420, "Cigarette Smoking Habits and Urine Characteristics" (Dales, Friedman, Siegelaub, Seltzer, Drey) Nepbron 20:163•170, 1978 "Ch'aracteristies P:edictive of Coronary,Heart Disease in Ex-smokers Before they. Stopped::;moking; Comparisoa vith Persistent Smokers and:Nonsvokera. (Priedman„ Siegelaub, Dales, Seitzer)JonrnaIChronic Diseaaes "The Absence of Excess Coronary Heart Disease Among Elderly ih the Continuation-of Cigarette S.okieg. A Eeply.". The American Journal of the Medical Sciences. 1978, "Stopping Smoking and C.H.D." The Lancet, 1978 0
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118 ,;~ty, r , _ T NI e -- ` + a . bS M, ~ ~ R ~ - k /0 o. e o .M __-i I % ~ i I I ~ I I F' ~ ~- ca~!ryi - H r ~ I ~. tl 1 Jill E i , I I at B.S fol whe: par Stai of S C31i F'bsp Cons I di tion of' S
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. 119 T j n- Statement of Jack Matthews FarrSs,.M.D:, Professor of Surgery, University.of Cal!iforniaa in San Diego~ My name is Jack Matthews Farris. II am Professor of Surgery at the Universi'ty'of California in San Diego. I received my A.B., B.S. and!M.D. degrees fromithe University, of Nebraska. During the following ten years I was associated with the University of Michigan, where I ultimately became an Assistant Professor of Surgery and participated in the teaching activities, directed research, and was involved in depth in both!graduate and'undergraduate level~s in the assumption of i'nd'ependent responsibildty for the surgical care of' approximately fifty percent of the total population,in general' surgery at the University Hospital in Ann Arbor. During World War II, I served approximatel!y 24 months overseas as a surgeon !'n the University of Michigan unit and ultimatel!y traveled through .uroce with the Armored Division of General Pat'ton, and rece,ved the Bronze Star. I practiced surgery in the Los Angeles area for 25 years as Staff Surgeon at the Good Samaritan Hospital!, Los Angeles; Chief of Surgical Service at the Harbor General'Hospital, Torrance, California; and Chief of Surgical Services at the California F'.ospital! Medical Center, Los Angeles. I also served as Senior Consultant to~Surgery,for the Veterans Administration, for wnomi 1 directed the surgical activities at Several of their institu- tions, in, California. I am a member of the Cancer Committee of the American College of Surgeons and formerly served!as Section Chief in Charge of I ®
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Cancer Activities for the College Surgeons for Area XI, which includes California:, Arizona, Nevada and Hawaii. I am~also a:mernber of numerous medical societies,,where I have served on advisory committees. I am~past Chairman of the Western Region of the American College of Surgeons, Regionali'lzation Program - Commission on Cancer. I have published approximately 73 papers in scientific journals and have contributed several chapters for surgical textbooks. My full Curriculum Vitae and list of publications are attached. I have followed with increasing interest the current controversy concerning public smoking and am surprised as we1Q as disturbed that legislation has raised its ugly head in an attempt to restrict smok- ing,in publi~c places on the theory that such~liegi'slation is necessary to protect the health of nonsmokers. If such legislation must be considered, it should be considered in light of all'.the scientific evidence on the subject, rather than in an atmosphere of unquestioning acceptance of policy formulated by government officals who may have incomplete scientific knowledge. In the past„ dissemination,of inaccurate and incomplete scientificc knowledge has created unnecessary fear and a public outcry for the elimination~of claimed environmental "health hazards," many of which claims have later been proved invalid. For example„ increased scien- tifi'c knowledge has shown that cholesterol may well not be the health hazard'that it once was thought to be. Publicity of inconclusive studies led to the unnecessary ban of cyclamates, red dyes, and cer- tain hair preparations. Dr. Marvin Schneidermann, of the National Cancer Institute, has for many years held the view that smokinR. C3L rye, ~ur c !t ::an:
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er than lated by edge. I htific Dr the )f which >d scien« ie health xsive i Lnd cer- 121 caases bladd'er cancer. Last year, in commenting on the saccharin controversy, he said: "Bladder cancer has, in fact, increased. de've generally attributed this to smoking, but perhaps we were arong,"1 Before plunging,into a morass of restrictive legislation, it is important to determine whether, in light of all the scientific kncwledge to date on the effect of atmospheric tobacco smoke on the nonsmoker, there is a solid basis for such legislation. Along withlothers, I do not believe it has been provedithat acr:osaheric tobacco smoke is a health hazard to nonsmokers. An Sn`arnational group of scientists supports this view; andi as a r..at~er of fact, came to this same conclusion at a workshop they attended in1974 to consider this very issue.2 The Secretary of Health, Edueationiand Welfare has urged a ban on smoking,in federal office buildings throughout the country because he is under the impressaon apparently that smoking,affect's the health of nonsmoking federal employees. It is of interest, however, that other federal agencies apparently don't agree with the Secretary of Health. The Federali Aviation Administration joined t::e Department of'Heal'th Educa*.ion and Welfare and the National :nstitute of Occupational Safety and Health in examining smoking on air~)lanes. This group study in 1971 concluded that "inhalation of 'he byproducts from tobacco smoke generated as a result of smoking atoard commerei'~al aircraft does not represent a signifi'cant' healith hazard to nonsmoking passengers."3 Furthermore, after examining the effect on nonsmokers of smoxing,on busses The Interstate Commerce c,^:nission came to a similar conclusion.4 And just this year, the German Society of Occupational Medioine,. -3- I
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122 an organization~of some 700 members, primarily scientists concerned with occupational hazards and their relation to disease and man, earefulliy looked'at smoking in the work environment. The Society decided that there is no scientific justification for prohibiting smoking inloffices and other places of employment.5 The work of Hinds andiFirst of the Harvard School of Public Health - which was funded by the Massachusetts Lung Associ'~atiorr - lends further support to these important opinions. Using nicotine content as a tracer, they measured tobacco smoke in a wide range of public pliaces including restaurants, cocktail and student lounges, and bus and airline waiting rooms and found that the concentrations of tobacco smoke parti'~culiate were infinitesimally sma11.6 This study was reported in New England Jiournal of Medicine. I quote from Harvard Medical School's Dr. Gary Huber's editorial comment on this study (Hinds and First): "Under the most severe concentration of exposure in their study the nonsmoker could con- sume an amount of tobacco so smalli that the risk of any adverse = health effect would be nonexistent, on the basis of any available data in the literature today."7 In light of these conclusions by independent scientists and - government agencies, i't is not surprising that some of tobacco's severest critics have acknowledged that smoking is not a health hazard to nonsmokers. For example, Dr. Ernest L. Wynder of the American Healith Foundation recently stated that he does not believe that "passive smoking really hurts the health of somebody who sits next to you"8 - and for that matter, Dr. Jonathan Rhoads, Chair- man of the National Cancer Advisory, Board, admitted that, as far
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123 th e 1. ,imally "~ Medicine. •torial severe Idi con- verse ailable ts and acco's ealth f the t believe who sits Chair- as far r _s he knows, tobaaco! smoke i'n the atmosphere "'is not ini fact a_tual'ly harmfuli."'9 Claims have been made that atmospheric tobacco smoke causes lunb cancer in, nonsmokers. These claims border on the ridiculous. ::•ring more than 25 years as a practicing surgeon, I have treated thousands of poeple with cancer at various sites, i~ncludi'mg the .:cbs. I may state categorically that the cause of cancer is not kncan, That is why there is a "war" on cancer. There Is no evidence that atmospheric tobacco smoke causes : ra cancer in the nonsmoker. Furthermore, there are many holes _.. :he hypothesis that cancer of the lung i'inismokers is caused bysmoking. Even Dr. E. Cuyler Hammond', of the American Cancer Society, has stated'that there is "ho shred of evidence" that a nonsmoker can get cancer from:"seeondhand" smoke but there is a lot of evidence ttiat he cannot.10 And one recent study reviewing data fromiseveral' ;.ricr studies, including an epidemological study by the American =ancer Society, found "no evidence . . . that nonsmokers who are cOcstantly exposed to t'obacco~smeke have a higher incidence of ..rcncial cancer.,°11 -In summary, there i's no scientific proof either that atmospheric tobaccoismoke causes lung,eancer ininonsmokers or that it represents a s=anifibant hazard to health. I't is my opinion, and the opinion~ -•" many others„ that tobacco smoke in the atmosphere does not pose a -•...._t to the health of nonsmokers. Therefore, I think it wouldibe -'^aporopriate, ineffectual, and misleading,to base legislation cur- ='-i'lin3 smoking in~publiic places on the premise that it does. -5- -4 0 I
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124 References 1. Gillette, Robert, "The Ban on Saccharin: How? Why?," The Los Angelies Times, March 20, 1!977• 2. Corn, M., et al. Workshop su.^mary and recommendations. Report fromia workshop on E mrironmental Tobacco Smoke Effects on the Non-Smoker, Ber:r.ud'a, March 27-29, 1974. Scand. J. Resp. Dis. Suppi. 91: 88-90; 1974. 3. U.S. Dept. of Transportation, Federal Aviation Adminis- tration, U.S. Dept. of Health, Education, and Welfare. National Institute for Occupational Safety and Health. Health aspects of srnokino in transport aircraft. Rockville,,Md. AD-736097, December 1971. 85 pp. 4. U.S. Interstate Commerce Co:a.:.ission. Smoking by passen- gers and operating personnel on interstate buses. Washington, D.C. No. MC-C-6Z43; Motor Carrier Cases,. 114: 256-278; November 17, 1971. 5. Arbeitzmedicin; Social Medicine, Preventive Medicine 2/785. 39. 6. Hinds,, W.C., First, M.W. "Concentrations of Nicotine and~ Tobaceo Smoke in Public P_aces." New Eng. J. Med. 292 (16)~: 844'-845; 1975. 7. Huber, G.L. "Smoke and heat," Letter to the Editor, New Eng. J~. Med'~. 293 (1): 48-49;1975• 8. Wynder, E.L. Statement made on Barbara Walter's tele- vision program."Not for Women Only,"' WRC-TV, NBC. Network, Washington, D.C. April 18, 1974, 9!:00 A.M. Radio TV Reports, Inc. Wash'_'ngton, D~.C:., p. Ll. 9'. Rhoad6, Jonathan Jr., Cor.L ent during "A discussion of smoking and healthy" Newsc_obe, WTAF-TV, Philadelphia, Pennsylvania, p. 9, July 15,. 1975. 10. Hammondi, E.C. "What are the high~risk groups for public education? How does epidemiology identify them?"' In: Summary Proceedings of the Internationali Conference on~ Public Education About Cancer. UZCC Technical Reoort Seri'ies, Vol. 18, Geneva, 1975, p. 13. 11. Garfinkel, L. "Questions and answers on cancer: bron- chial ca in non-smokers." CA - A Cancer Journal for Clinicians 26 (3): 181-182; 197 •
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125 CURRIC'JLU7d VSTAE JACK R!ATITE';'S FARRIS, M.D. Premcdical Education: University of Tebras,<a - A.B. 1933 University,of Xebraska - B.S. 1934 ~!edieal Education: University of 1~ebraska - 1I:D. 1937 Internships: University of Michigan Junior - 19G7-1938~ Senior - 19b8-19391 Residencies: University of Dfichigan Assistant Resident - 1939,1940 Residera - 1'940-1941 1i941-1942 1942-1943 Fe1lowship inAnr.erican College of Surgeons - 1944i B:,ard Certificationc American IIoard~of Surgery - 1945 Teaching Appointrtents: Instructor in Surgery, University of bJichigan, 1941-1943' Assi'stpnt Professor of Surgery, University of T:icLigm-,, 19<?5-19n7 Assistant Clinical Professor of Ss;rgery, University of Southenii California, 1948-1950 Assistant Clinical Professor of Surgery, University cf Calilfornia Los .1ngeles, 11950,1953 Assistant Clinical Piofesser of Surgery, University of California at llos Angeles, 1954-1963 , Clinical Professor of Surgery, University of California, Irvine, 1966 - 1972 Prcfc;sor of Surgery,,Universitv of California, 1973 - 1975 Professor of Surgery, University of California, Sari Diego and Veterans Adiministration }"ospital,,San Diego, 1975 - Present 34-12L 0 .-78-9 I
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126 Hospital ApFoint~^,cnts: Senior Consultant in, Surgery, Long Beach Veterans f'.ospital Chief, Stmgical Service„ California P.ospital ~'.edical Center, Los Angeles, 1956. Chief, Surgical 5en-ice, Harbor General 6osrital', Torrance, California Staff Surgeon, Cood Sairarit<n , ]:ospital P'edical Center, Los Angeles Other Appointrents: Chairman, Region D: (F:1asRal,, Havaii, i':-:sHinston, Oregan, Cal!iforr.ia, Aeti'ada, Arizona) , fr.ericar. Ccl'leFe of Surgeons Fegionalizaticn Prograr.i - Ccrrrission on Cancer. Professional Education Co:-z.iittee, Am.erican, Cancer Society, ' California Division. 1•~aedica] and Scientific Advisory Panel, Merican Cancer Society Of Los Angeles County Board of Directors, r_'edical Research Association of California. ACerabershiP, Medical Societies: Society of University Stirgeons - 1945 Ajr:eriican,T=cdical Association Frederick A.., Coller Surgicali Socidty - 1947 LosA.ngeles Count~• Nedical Associatiion. California, Mec,ical Asseciaticn Par. Pacific Surgical A'ssociation - 1949 Arerican Surgical Pssociation - 1950 Los Anr;eles Surgical Society - 195Q Pacific Coast Surgical Asseciation, - 1951 International A'cadery of Proetclbgy Societe IhtexTationale De Chirurgie 5ociety of Surgery'for the A1ir,.er:tary Tract Pheer.ix Sungjeal Society 0ionornryj Reno Surgical Society ([P.onora2y)~ }'Gnsas City Surgical Society (Honorar\')I British Cclu;bia Surgical Society (E;onorary) Cvers Pssig !a; ard
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-;i 127. hlilitary Record ;,ank: Dlajor Actire Duty: Uniited~States Arr.y Medical Corps, 6/10/ 13 to 2/5/46 GvQrseas Duty: Eioropean Theater of Operations, 5/10/43 to 6/15/45 tss igruaents : University of b'ichigan~ - 298th General Hospitall, England BYitish b:ilitary Hospital, Shaftesbury, England Chief, 4th Auxiliary Surgical Grcirp, Third Arn.y, Europe r.,:ards and Citations: Bronze Star Medal ®
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128 BIBLIOGRAPHY 1. Farris, J.H., Biisgard, J.D. The Relation ofl Cartilage to the Repair of Bone. S.G.o. 66:173, 1938 Ferris„ J.M., Haight, C. Tuberculoma of the Lung!: Case Report. JI. Thorac. Surg. 9:108, 1939. 3.Farrils„ J.M. The Role of Viatmin K,in the.Tireatment of Obstructive Jaundice. Univ. Hosp. Bull. Uhiversity of Hichigan 6:33, 1940. 4. Farris, J.M., Coller, F.A. The Surgery of Modern Warfare. S,G.O. 72:15, 1941. 5. Farris, J''.MI„ Collen, F.A. The Management of the Jaundiced Patient, with Special Reference to Vitamin K. S.G.O. 73:21, 1941. 6. Farris, J.M. ProgressihSurgery.. Encycloped'iaAmeric.ana, New York American Corp. 1942, 7. Farris, J.M. Tissue Reactions to Suture Materials: A Prellim.i~nary,Report. Ann. Surg. l1i4:159, 1i941i„ 8. Tissue Reactions to Suture Material as Observed in the Anterior Chamber of the Rabbiit"s Eye: A Preliminary Report. Univ. Hosp. Bull., Univ. of Michigan 7:611„ 1941. 9. Farrils„ J.M.,, Meade,. W.H., Lond~, C.HL The Use of' Cotton as a Suture Haterial, with Particular Referenceto.itsClinical ApplicaYion., J.A'.H.A'. 117:2140, 1941. 10. Farris, J.M., Coller, F.A. Wounds of 4larfiare. J. Lab 6 Clin. Med!28':4N'1, 1943. 11. Farris, J'.MI., Ransom, H.K: Total Gastrectcmy:EffectsuponiNutrition. andlHematopoiesis. Surg.ery: 13:823, 1943...12'. Farris, J'.Mu, Buxton, R., Moyer, C..A.,.CoIller„ F.A. Surgical Tnratment of Long-Standin9 peep~Phlebitis o:Fl the Leg: A PreliminaryReport. Surgery15'c749', 1944. 13. Farris, J.M., Romack,. H. The Effect of Streptomyeim.in"Closed Loop" Appendicitis: An Exoeritrental~.Study.. Univ. Hosp. Bb11., Univ. of Michigan 12:90,. 1946.. 14'. Farris, J.M.,.Jones,.Ti.B., So.Te Observationson:Wound Healing: A Clini!eal Study with aHote on Topical Chemotherapy andlSecondary Closure. S.G..O. 84:203, 1947. , 16, Fa Pa 17. Fa en. I8~ Fa St~ 19~ Fai Moc 20. Far 28 21. Far TrE 12. Far Tire 2 :'' 23., Far Wh i 24. Far 25. Far Med 26. Far Med' 27. Far Bu9 28. Far 29. Far Amo~ Hbr 30l Far cu1, 31 . Far Am. 32. Far: 127 15.Farri',s, J.M.,,Rormack„ H. The Effect of Streptomycin on Experimentallly, Ihd.iccd Appendicitis. Surgery. 22:305, 194'7..
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16. 129 Farris, J,H. Transverse versus Vertical!Abdominai Incision. Proc. Pan- Pacifiic Surg. Assn., 4th Congress, 1947,. 17. Farris, J.M., Ettinger, J..,,Weinberg„ JI.A. The.Hernia Problem,.with RBf- erenee to a Modificaiion of the McVay Technique. Sur,gery, 24:293,,1948. 18. Farris,,J.M. A Method for Removal of' an Open Swallowed Safety Pin f'.rom,the Stomach. Bull. Moore-White M!:•d. Foundation 1:1!4, 1949. Ig. Farris, J.M., Bishop, R.C. Surgical Aspects of AbnormallTwihning., Moore-White Med. Foundation 1:3, 1950. Bull. 20. Farris, J.M.,.Bishop, R~.C. Surgical Aspects of Abnormal Twinning. Surgery 28;443, 1950. 21. Farris, J,Mu, Wilkins, F.B., Weinberg„ J.A. Conservatism in the Surgical Treatment of Benign Gastric Ulcer. Surgery. 30:256, 1951. 22. Farris, J.M., Wilkins, F.B'., Weinberg, J.A. Conservatism in the Surgical Treatment of Benign Gastric Ulcer. Bull. Moore-White Med. Foundbtion 2':35, 1951. 23. Farris, J'.M. The Surgical Treatment of Malignant Melanoma. Bull. Moore- White Med. Foundation 3:27, 1952. 24., Farris, J.M. Surgery,o:f )nguinal Hernia. Modern Medi;cihe..p 171, 1952. 25. Farris, JLM'. The Origin and Treatment of Malignant Melanoma. California Ned„ 78:110, 1953. 26, Farris, J.M., Drake, H. Peripheral Arterial Embolism. Bull. Moore-White Med. Foundation 4':20, 1953. 27. Farris, J.M. Gastric Cancer, with a Consideration of Total Gastrectomy, Bu.llll..Moore-White Medl. Foundbtion, 4:4'4', 1953. . 228, Farris, J.M. Pulmonary,Embolisrn. Western J'. S•C.O. 61':524, 1953. 29• Farrls,.JI.M. Discussion,of "Cancer of the Parathyroid Glands: 4' Cases Among 148 Patients with Hyperparathyroidism;, Dilscussion of paper by Cope. 0. P:ordi, G., Castelman, B. Ann. Surg. 13£1:661, 1953. 30. Farris, J.M, AUsefulNew Tissue Forceps. Eull. of Instruments ofParti-cular Interest tothe.Surgeon. 2:5, 1'95i).. 31. Farris, J.M. Gastric Cancer, with a Consideration of Total Gastrectomy: Am, J. Gastroent:. 22:203,.1954• ,. 32. Farris, J.MI Thrombosis and Embol'ism., Surg. Clin. t7onth America 34: 1271, 1954. 8 W
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130 33. Farriis„ J_M. Evaluation of Vagotom,y with GasCroenterostomy Performed! for Chronic Duodenal Ulcer. (Discussion ofl Stanley,0..Hoerr's Paper). Surgery 38:149, 1955. 34.' Farris, J.M. Isolated Pipodystrophy. A Form of Mesenteric Tumor (Dis- cussion of Paper by J.T. Crane, M.J. Agui,llar„ and DrvilleF. Grimes). Am. J'. Surg. 90:169', 1955. 35. Farris, Ji.i Smithy G.K. An Evaluation of TemporaryGastr.ostomry. Ann. Surgery 144:3, 1956, 36. Farris, J.ML, Smith, G.K. Vagotomy,,,Cllinical Results. California Hedicine 85=394-398, 195'6. Farris, J.M., Smith, G.K. Ma.lli'gnant Melanoma:- Rationale ofi. Treatment. Current Surgical Management. W,B.,Saunders, Go., 1957, pp 447-451. 38. Far~ris, J.M.,. Smi.th, G.K.The Rationale of Vagotomyand Pyloroplasty, iin t~he. Manage.ment of' Bleeding Duodenal Ulcer. J':.A.M~A. 166:8, 1958. ' 39. Farr~is, J..M~.~, Sm~~iith„ G.K~,, Vagotomy~andlPyloroplas~t~y in Chronic Duodenail Ulcer with Spec.iiallReference to Techniqpe. A.M.A. Arch. Surg.78:652y.1i959•, 40. Farris,.J..M.„ Smith, C.K. Current Surgical Concepts of Galllblladder Disease. The Medical Cllinics of North Americay W.B. Saunders, Co. 43:4, 1959. S 411.. Farri.s„ J.M.,.Srmith,.G.K., andlBeattie, A.S. Umbi.lical,.Hernia:. An Inquiry into the Principle of Imbricationianda Note on the Preservation of the Unbi'llicall Dimple. Am. JL Surg. 98:2, 1959• 42., Farris,.J.M., Beattie, A.S., and Frempter, G.R. Hypatohyperchole;terolemie Cirrhosis - Report of a Case Implicating Cholrpromazine as the Etiolgic Agent. California Med'. 9'1:154-155, 1959. 43. Farris, J.tl., Drewer, L., et al. The Patholbgi'c Effects of MetallicForeign Bcdiesin thePu~lmonaryCireulation. Jr. T'hor..and Cardiovas. Surg., Vol. . 38,,No. 5, pp 670-6841, 1959', 44. Farris, J~.H., Smith, G.K'. Vagotiomy,and Pylbl'oplasty:A Solution.to theflanagement of B'leeding Duodenal Ulcer. Ann.,Surg. 152:1, 1960. 45. Farris, JLM. Panel Discussion on Pancreatic Disease. Am. J'. Gastroent. 34:4 198G 46. Farris, J'.M'., Comar~, D. Hy,pot:herm,iaiin Acute Surg;iead Emergencies. W. J',S.G,os 69:67-72, 1961. 4,7'. Parris, J.M., Smith, G.K. Re-evaluation of Temporary'Gastros.tomy'a.s a. Substitute forHasogastric Suction.. Arm. Ji. Surg,. 102, 1961. Farni of Gt y, Farri Ulcer 57. Far, ni Archi. Farri Vagot 52. Farri Llippi 53. Flarri gery, 54. Farri Vagot III, Farri ment Farr1 A.KeI 0. P' 1966. Farri Rev i e >°.Farri and P 1',16:4 Farr i the .. Farri Secor. Co., ll Farri~l AVn. J Farri'~.. l:nn. F r r i i Pep ti'.
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or cine t ~I959 t Pase. iry mic t 131 .?, F~rris„ J.M., Smithy G,K. Role of Py.l'oroplasty in theSurgica.lT'reatc.ent of~Gastric Ulcer. Ann. Surg: Sup. 1'54:6„ 1961. Farris, J.H,, Smithy G.K. Vagotomy and Pyloroplasty'for Bleeding Duodenall Ulcer - A Note on~Selective Vagotom~y,. Am,.J, Surg~. 105, 1963• - Farris, J.M., SmitHy G,K'. Some Observations Upon Selective Ga.st'ric.Vagotomy. Arch. Surg. 86, 1963. Farris,.J~.M'., Smith, G.K. The. Treatment of~Gastric Ulcer (in situ)~) by. Vagotomy andiPyloroplasty: A Cli~nical~'. Study..~. Ann. Surg. 15:g:3, 1963. ~. 52'. Farris, J.M., Ulneilical Hernia. Nyhus and Karkins' Bbok, HERNIA. J.B. Lippincott, O.o. pp,315-320i 1964• ~3,. Farris, JLM., Discussion, Jaboulay Py.lbrop.lasty.- Atlass of Techniques In Sur^ gery, 2nd Edlition~ 1964. Madden, J.L., Appleton, Century, Cnofts, Ine. i+.. Farris, J.M., SmitH~., G.K. The Treatment of Gastric Ulcer (in situ), by V_,uotomyand'.Pyloroplasty: A Clinical Study.- Current Surgical Management I!I,I „ W.B. Saund'ers Co. pp3.35-34'2, 11965.. . 55, Farris, J.M'., Smith, GIK. Tempora.ry,GasSrostomy... Current Surgical Manage- rent III, W.B!. Saunders Co. pp 355-359,. 1965.. Farris, Ji.M., Smithi, G.K. Some 0ther O.perati'ons for Gastric Ulcer: . A,KellinnrPlad'lenen Operation. B. Wedge. Resection and Pyloropdasty. Pyloroplasty(w~ithiulcer in situ)'. S~urgicallClinics.of NorthiAmenica. I I966. 57'. Farris, JI,M., Hietiert, 8,41, Hypert'rophic Py.lb:rik Stenosiss in~ theAduEt: Review of 22'cases. The Amer. Surg. 32:10, 1966. 53. Farris, J.M., Smith, G,K'. Appraisal of' the Long-Term Rpsultsof Vagotomyand Pyloroplasty ini100,Patients witih Bleeding Duodenal Ulcer. Ann. Surg. 1116:4, 1967. 53• Farris, J.H., Nagel, C.B. Clinical Experiences.wilth CorrectiveSurgery_forthe Dumping Syndl-ome. Am. J. Surg. 116:229, 19~63.. . !DL Farris,. J.H. Comment, Ohapter~ 9 entitled Gastriic U.Iker„ Ilyhus andHarkins' Second Edition of Surgery of the Stomach and Duodenum., Little,.Brcwm Gco. 1968. 61, Farris, J.M. Reappraisal of the Long-Term EFlfects of SelGctive Vagotomy. Am. J. Surg. 117':2', 1969- 62. Farris, J.M. Selective Gastric Vagotcry with Antrectomy or Pyloroplasty. Ann. Surg. 174:4', 1971. 63 . Farris„ J.H., Lessons Learned fromthc Use of Vagotomy iin the Treatment of Peptic Ulcer. Am. J'i. Surgs 124:121, 1972. (Discussion onl'y,): d a 0
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132 64. Rarriis, J.M. Procedures of Value for the Prevention and.Cure of Dumping! after Vagotomy and Pyl'oropl'asty,., Am. J. Surg. 124:279, 11972. Discussion ondy, 65. Farris, J'X. Uong-TerimiAppraisa.lof the Treatment of Gastric Ulcer in- situ by Vagotomy and Pyloroplasty. Am. J. Surg. 126:292-200, 1973. 66. Farris, J.M., Saik, R.P'., Greenburg, A.G., Peskin, G.W. Spectriumiof Cholangiltis.Amer. JL Surg~ 130t14'3-15Q,. 1975.67,. Fa.rris,.J.M.,, Truncal VagotomywithDra.ina.ge for the.Elective Treatrent Duodenal Ul!cer Disease. Controversy iniSurgery, Varco & Delaney, W.B'. Saunders Co. 1'976. of 68~ Farris, J.H., Gascrectnmy,G Py,lbroplasty: Surgical Techniques Illlustrated. Cittle, Brown E Co. 197b. 69. Farris, JlM:., Saik, R.P., Greenburg, A'.G...,,Peskin., G,W. The Practicali'ty of the Oongo.Red Test, or Is your Vagotomy.Complete7' Amer. J. Su.rg. 132:144, 1976. 70. Greenburg, A.G., Farris, J'.M. Special Commentary :"Complications of the Jaboulby Procedure" 3rd!Ed!ition of Stomach and Duodenum. L.M. Hyhus, Ed. 71. Sai'k, R.P.,,Greenburg, A.G., Farris, J.M., Peskin, G.W. Adequacy of Vagotomy Tested with Congo Red. Ohir. Gastr:oent. 12:1„ 1978. The Whar DseAanE I t versity istrf at ter, I II cther b: publict. Since CIchemica; .. the Uni, and boo)' Mu, restric in semi taurant organiz nonsmok fic fiD this ma T4+ s moking claim t sible i enclose as body control On causes places raise c is a nc the b1c tain fx rate at menta1i elevate example is accc
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133 UNIYERSITY of PENNSYLYdNId PHIIADELPFiIA 19104 The Wharton School CC (215) 243-ffi22 DBPAYTNBNr OF SIA71177i3 STATP•NIENT Richard ,1,Hickey,,,Research Investigator I am Richard J. Hickey., a research investigator at the Wharton School,,. Uni- versity, of Pennsylvania, Philadelphia. I- received a Ph.D. in biophysical chem- istry and microbiology.at Iowa. State University, Ames,, Iowa, in,1941.. T'hereaf- ter, I performed~research and.development.work on antibiotics, vitamins and other biochemicals. In the mid-1960's,.I became involved.in the air pollution - public health..problem inresearchinsti-tutes of the University of Pennsylvania. Since that time. D have been.investigatingn the relationships of environmental chemicals and other variables to chronicdisease risk at the Wharton School of the Universi-tyy of Pennsylvania. I havehad.published'numerous journal articless and book chapters, many of whichpertaim to environmental pollution. Much publicity, has been given in recent yearsto,the question of whether to restrict.orban tobacco smoking in areas used by the generall public, particularly, in semi-closedenvironmentsd such~as buses, railroad cars, airplanes, and res- taurants. The objections to "public smoking"im.such areas.arise largely f~romm organized anti-smoking groups. Emotional claims have been made that the average nonsmoker's health.is harmed~by exposure to-tobacco smoke... SubstantiaL scienti'- fi~c findings lendno.substanee to~suchclaims. L wish to,present my vi'ewss on this matter. Two principal kinds of allegations:have been made by opponents of public smoking, and these must be carefully distinguished. On the one hand,, opponents claim.that tobacco smoke is a nuisance beeause.of its odor, appearance.or pos- sible irritative effects. These effects are cited especially with reference to enclosed.areas that are.unventilated orpoorlyr ventilated. But annoyances such as body odors, cooking odors, and aromas from tobacco smoke can be adequately controlled byy proper ventilation. On the other band, a.more serious.claim: has been made that tobacco smoke causes disease in.nonsmokers. Typically, those who oppose smoking in publicplaeesexpress concern that carbon monoxide.in environmentaLo tobacco.smokewill raisecarboxy,hemoglobin levels in-nonsmokerstoharmful levels. Carbon.monoxiden is.as normal product of human metabolism,, leading to carboxyhemoglobin (COHb): in thebloodstream. Without any exposure to~environmental: CO.,.the blood may con- tain from 0.28.to.1.08: carboxyhemoglobin. However, individuals differ in the rate.at which their systems accumulate and metabolizeCOeven when the environ- mental carbon monoxide leveL is held approximately constant. Thus,.moderatelyy elevated CO levels do not.resul~tt in high COFib levels for all people exposed. For example,, smokers.have been found who display Low C013b levels. Fyrthermore, there is accumulating evidence that some nonsmokersdi-splay.more than 4% COPibunder low 7no 0 H 0 I
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134 levels of atmospheric CO (e.g.,. Less than 5 ppm). Genetic or constitutional factors,, then, can apparently influence individual COHb levels. Genetic fac- tors are known toinflvence individual levels of inethemoglbbini another hemo- globin~modi:fication which, likeCOHb, does not transport oxygen. An:individual's COHblevel also reflects his continui'ng exposure to motor vehicle exhaust and industriaL emissions,as well as tootner importantt soureesthat contribute to.urban.airpollution.. Tobacco smoke is an insigni- ficant source of CO as compared;.with these other sources. The combined re- sults ofstudi:es measuring tobacco, smoke components in~the indoor atmosphere under realistic conditions show.that concentrations may reach about 10 ppm: CO. At this concentration, an averagee individualwould,ha.ve to be exposed for eight eonsecutive.hours without ventilation in order to reach a COHb leveL of 1.9%. certainly well below the World Health Organi'zation~standard of 4%. Two recent European studies demonstrate that nonsmokers in work situations where tobacco smoke was present throughout.thedayt did not experience elevation of blood COtIl7. The German study showedd that theCOHb levels of office workers were higher upon arrival at work than when theyleft.at the end of the day (0.828to 0.634),, even though they were exposed:to cigarette smoke during the day. The second„ a Finnish study, found no increase in COHblevel5 in,nonsmok- ing office and restaurant workers in, spite of lengthy, exposure to environmentall tobacco smoke. Although~the restaurants were "smoky," the authors concluded that restaurant workers were not exposed to CO concentrations which exceeded the.occupational standard;(50 ppm.CO + 6 percent units COtUsL6'hrS exposure).. Those who claim public smoking leads to disease in the average nonsmoker often seliectiveiy cite studies in which~persons afflicted with~certain ill- nesses are subjects. For example, in the case of angina patients these studies have several eharacteristicswhichrender them questionable at best as scienti- fic support for the argument that nonsmokers in general face a:.hazard from CO exposure in public smoking!situations: (i)) alSi the people studied had severe coronary artery disease beforeexposure: (2)) some subjects were smokers rather than nonsmokers; (3)', the subjects being,testedd andthepeople administering, the experiments knew the purpose of the testss and knew,who was acttuallyy being exposed. This failure to use the "doublebli~nd" precaution permits an unknown, psychological reaction factor. If angina.pati~ents are to be studied,, compara- tive information should be provided of influences on angina of tension,, worry, fright, and other behavioral variables. It is noteworthy that many public health scientists disagree with claims that public smoking is a heaith~hazard for nonsmokers. For example, Dr. E. Cuyler Hanunond of theAmerican Cancer Society stated at an international caneerconferencein 1974 that there is:"'no shred of evidence" that a nonsmoker can get cancer fzom,"second-hand"'smoke and there is a lot of evidence that he can- not.. Dr. Reuel Stallones,.an advisor to the:Surgeon General's Committee,, was quoted as saying in,1974,. "In very direct terms there isnomedical proof that nonsmokers exposedto:cigarette smoke in ordinary relation with smokers suffer anyy damage:"And Dr. Jonathan Rhoads,.formerPresident of the American~Cancer Society, said in1975, "TO my knowledge, it ['passive' smoking] is not, in fact, actually harmful." Manyother scientists have published similar views. Confusion,over the issue i~ss most likely to occur among:thoseof the public whoo are not professional scientists. from find' is i and that cars node heal Pcrt iog, p2rs rent t' at
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a] I MN 135 prcponents of regulation of smoking in public places often cite findings tMm unrealistic tests conducted~ in unventilated enclosures.Dse of such (taCinqs.which overlook or minimize results where ventilation was.realistic yj inherently biased~andd therefore worthless.for pubiicpolicy purposes. Hias .ad motionali~sm asidA;, there is no ~ scientific evidence of which I am, aware, art tobaccosmoke or any.y of its components occur in buses,, railroad passenger (.rI,.corTCerciali aircraft,, restaurants,, and otherpublia places with~at least .uleratee ventilation at sufficient concentrations to constitute an authentic e..1th hazard to nonsmokers generally. Clbjective,, substanti~ve evidence sup- ycrticg allegations ofheaLth hazard too nonsmokers from realistic public smok- ;aq app.earsto be non-existent, apart from reactions of a few abnormally hy- pa.ensitiveindividuals who mayalso be hypersensitive to many other envi:ron- .er.tal faotors. In fact,, objieetiveevidenee is compatible with the position cms "public smoking" does not constitute.a significant health hazardL Ri'chardJ. ~Fickey, Ph.Di August 21, 1978 / I 0 fl 0 I 11 0 0 ® ® F
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136 STATEMENT OF LOUISE HEROU SAUNDERS President, Charlie''s Cafe ExceptionaLe, Inx_, Minneapolis„ Minn. My name is Louise Herou Saunders. I am~President and Chairman of the Board of Charlie's Cafe Exceptionale, Inc. in down- town Minneapolis„ Minnesota. I am a lawyer and a member of the Hennepin County Bar Association, Minnesota State Bar Association and the American Bar Association. I was a member of the board of the University of Minnesota Law School Alumni Association. Charlie's Cafe Exceptionale is an "Award Winning'," restaurant. In August of 1978 - Charlie's receive&its 2Bth consecutive Holiday Award. Also, this year Charlie's has received its third consecutive Business & Executive Award and the Four Star Mobil Award - plus other honors. Charlie's has been in operation for over 44 years. The restaurant seats approximately 374,patrons and is totallq, committed to the gracious service of its clientele in a relaxing atmosphere. On August 1, 1975, the Minnesota Legislature enacted'the Clean Indoor Air Act and later the Health Department implemented reguliations in support of that Act which limi'ted smoking in public areas, including restaurants. It is my opinion that such legislation is unnecessary, as it is the market place that determines to what extent a business should go in providing no-smoking accommodations. If the demand is present, a restaurateur will gladly accommodate those individuals who desire no-smoking accommodations. According to a survey conducted by the management of Charlie's Cafe Exceptionale, less than two percent of that restaurant's clientele actually, requested no-smoking facilities during the period of its survey. const Depar be eq reque prese time., prove no-sm reguliemplo, that , hos te; that ' and ae except occurx enforc other it is to an police dilema should being
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rs e ?l. 137 At Charlie's, we expended approximately $10,000.00 in construction costs to comply with the regulations promulgated by the Department of Health, thereby creating a no-smoking area that would be equal in every way to the smoking,area.of the restaurant. The requests for this facility have been very light and our no-smoking area presently consists of six tables which accommodate 20 patrons at one time. This space represents under 6% of our seating capacity and has proved to be more than adequate to accommmodate customers who desire no-smoking facilities. Another aspect of the Minnesota Clean Indoor Air Act and regplations has been to place a heavy burden on both management and employees. It is these individuals who must enforce the law. Proposing that a guest be arrested is not my idea of being a gracious host or hostess. The Chief of Police of the St. Paul Police Department said that "violation of the law ...is a misdemeanor of the lowest order and'as such will receive absolutely no attention from our Department except as it might be necessary to respond to specific complaints occurring within our jurisdictions." Enforcement of the statute an&regulations by regular law enforcement agencies seem an unfortunate use of tax dollars. On the other hand, it seems to me a bad precedent to even have a law if it is not going to be enforced. EnEoreement, of course, would lead: to an unfortunate and substantiali use of tax dollars for inspectors, poliicement, prosecutors, courts, and the like. I, for bne, believe the dilemma is best served by not passing a law. The problem of public smoking, if it aetualily be a problem, should be Ieft, in my judgment, to the restaurateurs rather than being the subject of restrictive legislation. A restaurateur, for 0 0 I 0 0
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example, is better ablie to determine what, if any, smoking accommodations or nonsmoking accommodations should be provided in a given situation. What might be reasonable for one restaurant could be total~ly unreasonable for another restaurant. Any arbitrary setting of a percentage of one'ss business aside as smoking or nonsmoking would, in most instances, create an economic hardship. A restaurateur can ill afford to have areas sit idle whilie turning away business. Usually smokers nor nonsmokers do not patronize a restaurant as a homogenous group.. Smokers and nonsmokers dine together as a practical matter, and it has been our experience that tables isolated in a nonsmoking area are not in~great demand. It would be highly injurious to a hospitalii'ty business to have customers waiting to be seated in a smoking-permitted area while an arbitrarily designated smoke free area sits idle. It has has been our experience that when customers are kept waiting too long for a table they simply leave. The people who leave are lost ass customers -- and revenues are lost. Over the years I have had a great many personal friends who serve in government and have a great respect for government. However, I sincerely beliieve that this type of legislation is not the proper domain of either state or federal government. This type of legislation, in my judgment, is another encroachment on our individual freedoms. It seems to me that the real answer here is simply one of courtesy by smokers and tolerance by the nonsmokers. No law will promote courtesy and tolerance but these kinds of laws certainly can and do work a very real economic hardship on the business people involved'. •r Profes:, ~anee:"r ep and relat 3GDPOXj IID3 :n 1977, :,ects of rtuere is factor j: ] Current publlc pi °aa.:2imat:
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139 STR=4T GF O:aFD N. SChT',AUZHFk. PH.ID. Professor of Chemistry, University of California, San Diego 4- s YW name is Gerhard N. Schrauzer. Since 1963, I have been Professor of Chemistry at the tiniversity of Califorr-la, San OizSo. I hold a Ph.D. deg:xee in~cherdstry from the University of }Lrich (1930), and am the president and founder of the International Association of Bioinorganic Scientists. I am also a member of the ;cerican Chemical Society, the Association of Clinical Scientists, t`e knerican Public Health Association, and Affiliate Fellow of the ti^Bri'can College of Nutrition. My main research interests are in cancer-preventicn, ca^,cer epidemiology, trace minerals in human andiarLimal nutrition and related fields of experimenta.l chemistry. I am the author of approximateLy 200 research publications and have edited 2 books. i.n 1977, I organized a Conference on Inorganic and Nutritional As- pects of Cancer. Claims have been made that tobacco smcke in the atmos- p^ere is haxr.ilul to ncnsmokers, i.e., that such smoke is a causative factor in the induction of many diseases. Are these claims valid? Current legis3ative activity aimed at t he restriction of strpidng in Fub11c places might lead~one to believe that they are. However, esa~nination of the scientific literature on this sub,ject reveals that 0 0 0
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140 these a7legations are unfounded. In the United States today, pecple do not need to fear chronic or acute poisoning due to the presence of tobacco sm.oke in the indoor atmosphere. Indeed, smoke-filled rooms have become a rarity due to substant'ia1 improverents in air ventilation and~air conditioning technologies. Since active smoking is claimed to cause lung cancer in smokers, it might be claiaed that atmospheric tobacco s^oke - either frcm 1lghtedicigarettes or exhaled from smokers - could cause this disease in nonsmokers. However, the etiology and pathoger.esis of human lung cancer is as yet unknowny marLy authorities agree that cig- arette smoldng is only one of the m3r~y factors that might possibly contribute to the development of the disease. In~¢any countries significant differences in the lung cancer incidences of males and females are observed. In the Nether- lands, about 15 times more men die of lung cancer than women. In Chile, Japan and Israel' about 3.times more men die of lung cancer than wcoen. There are also differences from country to ceuntry aarrng members of the same sex. Thus, the :m.].e lung cancer mortalities in 1964-1965 were the lowest in Portugal. (10.06 per 100,000 population, age-corrected) and the highest in Scotland (75.55 per 100,000 pop., age corrected). These large differences in mortalities carnot be explained by differences incigarette consurrpticns, types of tobacco used or the variation of smoldng habits in these countries. Obviously, other factors (genetic and dietary)eontrol the hLzan lung cancer Lncidence. In ~'_^egen on inhs c:..^.ogenesis, Dr bcratory - t = tcbacco smok _wntify a carc Whi ..f lur.g cancer '`at the nonsmo: ~ 3 cancer risl :a.-srcrond has saii stn,ker can get c '_o*t of evidence recent study tlm cluding an Amerj "!:o evidence. . 'a=~-`~er incidence Why ' resphere causes ^°norts - mostl nalss - of suspe sr-ke. For exam r`eferred to a st r.itrosemiR:es and 39-l21iO-78~~-IOi
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Incidence. 141 In arj.¢a1 experiments, tobacco is not a pulmonary ear- cir.ogen on inhalation: In conmenting upon experimental tobacco car- cinogenesis, Dr. Lijinsly - who is now with the Cak Ridge National Labrratory' - told Congress in 1971, that "in spite of 20 year's work on z;obacco sanking we cannot identify or nobody has been able to Identify a carcinogen to explain the incidence of lung cancer in man." Whil'e the role of active cigarette swoking'in the etiology of lung cancer is still controversial, it may be stated with confidence t~at the nonsmoker's exposure to tobacco smoke has no effect on the lun.g cancer risk. Even the American Cancer Society's Dr. E. C. Ha..^mond has said that there "was no shred of evidence" that a non- srcker can get cancer from "second hand" sanke and that there is a lct of evidence that he cannot. This view is consistent with a recent study that reviewed findirags fron several other studies, in- cluding an American Cancer Society epideudological study, and found "no evidence: . . that nonsmokers exposed to tobacco smoke have a higher incidence of bronchial cancer." Why then do we bear claims that tobacco smoke in the at- rosphere causes lung,cancer in nonsmokers? (he reason might be reports - mostly in the lay press but sometimes, in scientific Joux- na.1s - of suspected carcinogens In the atmosphere from cigarette snoke. For example, a recent editorial in the British Medical Journal referred to a study by Ernunnemazan, et al. reporting the presence of nitrosamines and benzo(a)pyrene in the atmosphere from cigarette saroke. I 8 34-121 0 - 78'- l0 I e M
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142 With the advent of sophisticated detecticn techniques, ccm.pounds such as nitrosamines and benzo(a)pyrene can now be identified at levels lower than ever before. This tectnological advance in detec- tion does not mean, however, that the presence of such substances im tobacco smoke or in other areas of our envimnment has etiologic sigiificance in cancer. As to nitrosamines, their presence in nitrate cured meat h.as generated a long lasting controversy about the safety of using nitrate in food'technol!ogy. However, while nitros2mines have been found careirtogenic in anim3l tests, even the British Medical Journal editorial admdts that they have not been "linked to human, cancer."' Accor3ing to the editorial, 8runnemann, et al. found that nitrosamines in sidestream smoke are 50 titr.es greater than nitrvsamines in the mainstream smoke. The editoriaL also referred- to their estimate that a ronsmoker in a smoky room~could inhale in one hour an amount of nitrosamines equivalent to s,king 15 filter cigarettes. It is important to point out, however, that &vnnem3nn and his colleagues also noted siggnificant dependence of the observed levels of nitrosarrdnes in sidestream suaoke on the experimntal ccn- ditions. Their data were accumulated by collecting-sidestream ssmke with air passing around the buu:^.Zng cigarettes at flow-rates of 1500 mL/min (=25 mIli/sec). Such flow rates are unlikely to occur under reallstic smoking conditions in rooms. The a.mcunt of nitrosa- mines observed at slower airflow rates was sigaificantly lower: At 1500 mL/ aere produc of air per 530, 250 ai cake reliaJ under real cigarette the atmosr room with in only a) this ccnm experimen ca.rcinoge able conc stances i charcoal as that one cigE air. Z1 (a)pyre; 'Ih.is sP exposedi i3ecat]sE.
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143 0 L; 1`, 0 mL/min, typically 680 nanograms of N+dimethyLnitrosamine re.-e produced per cigarette. At flow rates of 1000, 500 and 250 mL :.• air per min., the amounts of N~-dimethylnitrosamine dropped to =„o, 250 and 90 nanograrrs per cigarette. Hence, it is difficult to mio- reLiable estimates on the amounts of nitrosamines generated s,der :eal-life conditions. But, even if sidestream smoke from a ::,-aza,te did contribute 680 nanograms of N-dimethy]nitrosamine to =,e atmosphere, the smoking of as many as 100 cigarettes in a small :xcr, with a total air voltm,e of 800 cubic feet (28 m3) would result :.-i crly about 3 nanograms of the ccmpownd per liter of air. At :as concentration, carcinogenic effects could not be demnstrated~ experimenta]1,y. Likewise, benzo(a)pyrene - another well-lmovm anlmal carcinogen - is found in plants, soils, foods, and the air in vari- able concentrations. Eenzo(a)pyrene is formed whenever organic sub- stances are urdergoing eombustion6 It has been estimated that one :~rcoal broiled steak contains the same amount of benzo(a)pyrene as that generated by about 300 cigarettes. The Bri.tish Nsdical Journal editorial indicates that one cigarette may give off 100 nancgrams of benzo(a)pyrene into the air. Me editorial then states that this "smatl" amount of benzo- (a)pyrene "Gan be assumed to cause at least scme cases of lung cancer."' "^.is speculation, however, is inconsistent with studies of humans exposed to large amounts of benzo(a)pyrene in their work ernvironmnt. Secause roofers in the United States are e.xposed~to large amounts of
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144 benzo(a)pyrene by virtue of their use of coal-tar pitch, petroleum asphalts and other products, the question to what extent this raised their lung cancer risk was given serious attention by E. Cuyler HamDOnd and Irving J. Selikoff. Analyzing ep;<.deffiologic data for 5,707 roofing vrorkers, the authors noted only a slightly higher mox- tality from lung cancer aunng these workers co¢pared to all men of the same age in~the United States. They concluded, as a result of their study, that it is "unlikely that the smaLl benzpyrene eontent of air in urban areas has an appreciable effect upon lung cancer death rates." In light of this andiother studies reported in the literature, there is no reason to believe that the auch slral].er aalount of benzo(a)pyrene in the atmosphere as a result of eip,arette saoke presents a health hazard to the nonsmoker. In conclusion, there is no scientific proof for the cla3ln that atmospherie tobacco smoke induces diseases in the non- smolcsr. Thus, regulations fozmulated to protect„the health of the nonslmleer would accomplish nothing but act as a 71aYE.tation of personal freedom. GERHARD N. SCHRAUZER b. 3-26-32, in Franzensbad/dzechoslovakia, Naturalized U.S. Oitizen,, is Professor of Chemistry, at the Uniiversity of California, San Diego (11966-present),. He holds a Ph.D. degree in chemistry from the Uni- versity of Munich (1956)' and is the president and founder of the International Association of Bioinorganiic Scientists. He also is a member of the American Chemical Society, the Associiation of Cliinical Scientists, the American Public Health Association, the So. Calif. Council Against Health Fraud and Affiliate Fellow, American College of Nutrition. His main research interests are iin eancer-preventiiony cancer epidemio- logy, trace minerals in human and animal nutrition, vitamins, especiallyy vitamin,Bli2, and various fields of experimental chemistry. He iis the author of ca. 200 research publications and has edited 2 books. In 11977 he organized a Conference on Inorganic and Nutritional Aspects of Cancer. He iis known for his pioneering work on the prevention of cancer by the essential trace mi'nerall selenium and'in 1978 received'a special award from the American Cancer Society (S.Cliana Section). _. Tetracyclo 1403 (1958 (z:5)-Diph and Indust 3. Diphenyloc Soc. 81, 5 .. Bisacrylon Tetracarbo 5chrauzer„ C•~clooctat M.D. Rausc 5: Bisacrylon Soc. 82, 1 .. Bis-Duroqi. 8'., 6420 ( 8'. Ilhe.rdie CDiazoalkar Qhemischr 9. =urKenntr 94, 642(a .,,_ Pnfrarocsl und'Aerole S.. Eiciilei .2. Bin Beitr; 94, 1891 13. =ur~~ Kennn: nickel(O) 1- . Uber Re~ak~ Beitrag.:. Chen.. Be~rl 13. Salt9s of J. Am. Ch
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145 ent ten, rego a ~Cal ~. fge Memio- IecJ;a 1 1 y 2'books2 tpects of jed a 9 PUBLICATIONS Gerhard N. Schrauzer 1. Tetracyclone Iron~Tricarbonyl,. G.N.,Schrauzer,. Chemistryand! Industry,. 1403 (1~958).. 2:(2:5)-Diphenylcyelopentadienone Iron Tricarbonyl, G.N. Schrauzer, Chemistryind Industry, 1404 (1958). 3, , DiphenylacetyieneDerivatives of Iron~Carbonyl„ G,N. Schrauzery,J.Am.Chem, . Soc. 81„ 5307'(Q959). - 4.. 9isacry.lonitrilie Nickel'and Related Complexes from th'eReaction of Nickel Tetracarbonyl with Compounds containing Activated Double Bonds(I), G.N.. Schrauzer, J. Am. Chem..Soc. 811, 5'3101(i1959). Cvclooctat~etraen -Iron Tricarbonyl and Cyclboctatetraene*Diiron Hexacarbonyl, >I.D. Rausch and G.N. Schrauzer, Chem. an&Ind. 957.,, (1959)'.. 6. Bisaerytonitrilie NickelBistriphenylphosphine, G.N.Schrauzer, J. Am. Chem., 5oc. 82,.1008(!1960). 7 .. Bis-Ouroquinone-Nickel(O), G.Y..Schrauzer-and H. Thyret, J. Am.,Chem. Soc. 82,. 6420 (1960)1. 8. Lber die.Carbmnylierung von Carbenen und die.katalytische Zersetzungvon Diazoalkanen mit 8ickelcarbonyl!, Christoph RUChardr and Gerhard N. Schrauzer, Chemische Berichte 93~ 1840(1960).• 9. :ur Kenntnisvon Bis,acrylnitril-nickeli(0), III; G.N. Schrauzer, Chem,. 8er.94„ 642 (1961). 10. Infrarotspektroskopische Untersuchungen an Nickel(O)-Komplexen desAerylnitrils und Acroleins, HeinzP..Fri2z andGerhardIN. Schrauzer, Chem. Ber. 94, 650 (1961). Bis-(1,2-)Diphenylacryl'onitrile Molybdenum~Tet7aearbonyl, G.NI Sehrauaer and S, Eichler„ Chem. and Ind: 1270 (1961).. 12. Ein Beitrag zum Mechanismus d'erMeerwein-Reaktionz G.N. Schrauzer, Chem. Ber. 94„ 1891 (1961)I. 13. =ur.Kenntnis von Bis-durochinen-nickel(0)) und Syclooctatetraen -durochihon- nickel(O), G.N.,Schrauzer undH. Thyret, Zu. fUr Naturfbrschung 16b„ 353(1961),. 14. iJlber Reaktionen van Acrylnii[ril:-Komplexen des Niekel(0)',mit Alkinen. Ein, Beitrag rur.Aufkldrung, der Wirkungsweise.vonReppe-Katalvsatoren, G.NL Schrauzer, Chem. Ber. 94, 1403 (1961).. 3altsof the CyclooctatrieniumIron Tricarbonyl'Cation„ G.N. Schrauzer, J. Am.Chem. Soc. 83, 2966 (1961). I
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146 16. 17.. 18.. 19: 20i 21. 22. Uber Komplexe von Kupfer(I)-halogeniden.mit ungesSttigtea NiRri1'enundeinigen,Olefinen.M©dellversuehezumBindwngspro6lem,in Bis-acrylnitril- nick'el(0),,,Gerhard Y...Schrauzer undSiegfried Eichler, Chem.Ber,. 95.,,260 (1i962)... Radikalartige Nickelko;r,plexe von Derivaten des 1.1-Dicyan und 1.1.2-Tricyan- Ythylens, Gerhard N. Schrauzer, Siegfried Eichler und David A. Bro~ „ Chem. Ber. 95, 2755 (1962). KatalytischeReaktionen mit \orbornadien, Cerhard N. Schrauzer und Siegfried S], EicHler, Chem.. Ber. 95, 2764 (1962). Zum Mech'nnismus derCyclooctatetraen-Synthese nach Itl'. Reppe, Gerhard N. 31. Schrauzer und Siegfried EicHler, Chem.8er. 95, 550 (1962). Reaktion~von~Bis-dimethyiglyoxim-nickel.mit Borverbindungen, G.N:.Schrauzer, Chem. Ber. 95,, 1438 (1962). Neuartiige "Sandwich"-Verb'indumgen.desNickel(0). Zur Kenntnis von Durochinon- Sickel(O).-Komplexen nit cyclischen Dienen,. G.N. Schrauzer and H. Th-vret, 35.. Z. :iat.17b,.7.3 (1962)... Reaction of Diphenylacetylenewith Nickel Sulfides, G,N. Schrau:er and V'. ,,. Uber die.kate i t Si0-Vert and Peter G1Jcer Absorpt >lata.ll:<omoieG.S. Schraui Nay:eg,.J. Am. Chem. Soc. 84, 3221 (1962). 23. New Reactionsof Cyclooctatetraen-Iion Tricarbonyl,.C,D7. Schrauzerr and.5. Eichler, Angew:Chem. 1„ 454'(1962).. .. 24. Vitamin-E-Chinon-fiickel(0)-cyciboctadien(1,5), H. Thyret, G.N'. Schrauzer, Angew. Chem.. 74, 488 (1962).., 25. Durochinon.cyolopentadienyl-kobalt(IQ, H. Thyret, G.N. Sehr,auzer, Angew., Chem. 75, 641 (1963). . 26. Elecktronenstruktur, Spektren und Magnetismus von Chinon-nKomplexen des Sickels.,. Gerhard N. Schr,auzer and.Helmut Th'yret,.Theoret. Chim. Actal, 172 (1963). 27. Chinonk'omplexedes.Fickels mit.Cyclooetadine-(1.5), Cyclboctatrien-(1.3.5)) und mit Cyclooctatrienon, Cerhard N. Schrauzer undHelmut Thyret, Chem. Ber: 96, 1i755 (1963). 28. Zur Kenntnisvon 8is-acrylnitril-nickel(0). VII. Modellberechnung der Electronenstruktur von B'iis-acrylnitril-nickel(0), David:A'. Brown and Gerhard .. \. Schrauzer,. 2. Phys. Chem. Neue. Folge 36, 1(1i963)',. Coordinatio~. C~clooctate• and S. Eich. Freparation B:.odium„ an 86,. 326.5 (1 Coenz.ae B] SC56 (19647 Aach,eis ua~ G..\• Schrau Neuartige P JI A3u11er-h o.s (1963)... Eisencarbor Glockner, F' Metall-trie~ t';ge•.. Chec~. Tiris-stilbi FSack,..and Reaktionen ?ktalikomp. 195_ 192( '1I. Tri.s-dithi V. Dla~,eg, 42. So.e recen ,1dv. in Or 29.. Zur Kenntniseines Nickel~(II);chelates mit Kubanstruktur,Gerhard Y. Schrauzer undJosef Kohnle,. Chem. Ber. 97, 1727(1964)... -
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147 M Uber diee kata:ytische.Anlagerung.von Olefinen und:Alkinenan ?iorbbrnadien, mit NiO'Verbindungen und einem neuen NiII-Kemplex, Gerhard N. Sc}irau:e.rand:Pete.r.Clock'ner, Chem. Ber. 97, 2451 (1964). UoerAbsorptionsspek•tren und Konstitution von Organometall-*-F:omplexen. I. N2tallkomplexe mit Durochinon, Cyclopentadienonen und Verwandten Ligandeny G.N. Schr,auzer and G.Kratel,,J. OrganometallicChem. 2,.336(1964).... Coordinat'ion.Chemistry and Catalysis., Investigations'on the Synthesis of Cy.looctatetraene bythe Plethodlof W.. Reppe; G.N.Schrauzer,.P'. Glockner and S.:Eichler, Nide•+andte Chemie 3, 185. (1964). Preparation and Properties of Some Duroquinone pi-Oomplexes of Cobalt, R:.odium, and! I,ridiwn, G.N'...Schrauzerand.K.C. Dewhirst, J. Am~. Chem. Soc.. 86,. 3265(196s)~. 34. Coenzyme B i2-Dk1de11e, Gerhard N. Schrauzer and Josef Kolinle, Cfiem...Ber. 97, 3056. (1964}~~. 35. Nachweis ur.d Stabilisierung von Dithiobenzil dutch Komplexbildung_ HLW'. Binek, G.N.Schraucer, Angew. Chem. 76, 143 (1964),. Sa.. Neuartige P.lanarkomplexe von Uber gangsmetallen, V.P. Maywegy H.W. Finck, U. Nuller-tiesterhoff, and'W., Heinrichy G.N..Schrauzer,. Angew. Chem..76,.. - 3.5 (1964). 3;... E-senearbony.lkom iexe.von Cyclooctatetraein-Dimeren und von BulQvalen, P. Giockner„ R. Nkr~~nyi„ and G.N. Schrauzer:, Angew.,Chem. 76s 498 C1964). 35,. }L-:alil-trisdithiobenzilkomplexe,, mit H.W. Finck,.G:N. Schrauzer„ V: Mayweg, .Lgew, Chem. 76, 715 (19b4). ' 39'. Tris-stilbendithiolato Vanadium, Ji.H...Waters„ R. Wililiams, H.B', Gra,v„ H.W. F'.inck,.and GGN. Schrauzer_J. Am..Chem. Soc. 86, 4198 (1964). 40. Reakt'ionen von Uber-gangsmetallsulfidewmit Alkinen. Zur Kenntnisvow ?:btalikomplexen der o,9-Dithiodiketone, V. Mayweg_G.N. Schrauzer, Z...Naturf. 19b, 192(196'.4). :1. Tr,is-ditiiiobenzil-Komplexe,.desChroms, btol•vbdans und t4olifranes, H.W:. Finck, V. Hays:eg, G.N. Schrauzer,.Z. Naturforschung 15by 1080.(1964)'.... 42, SoWe recent advances in the organometallic ckemistryof nick'el, G.N'. Schrauzer„ Adv. in Organometalilic Ofiemistry2„ 1 (1964). I I
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148' 43. Organome.tallverbindungen von Cobaloximen und vom.Vitamin B12, G.N. Schr,auzer.r ;3~ Coordi und,G. k:ratei, Angew...Chem. 77, 130 (1965). Su~521 44. Die Konstitution von Vitamin B z Gerhard'M. Schrauzer, Richard J. IVindgassen~ . 3324'.(1965).. • und Josef F:ohnle,.Chem. Ber. 9i,s Si. P 'is-ac 45:.P.reparation, Reactions, and:Structure of Bisdithio•a-diketoneComplexesof ~ .566, Sickel, Palladium„ and Platinum, G.V...Schrauzer and V..P.Mayweg,.J. Aci. Chem. Soc. 87, 1485 (1965). •' 1[etai] 46, Trisdithioglyoxal Complexes, G.N. Schrauzer, V.P,..Mayweg and i1. Heinrieh,. ~:rand'. 7echni 47. Soc. ofChem. Industry, 1464 ('1965). Coordination~Compounds with DeloealizedGround States.. Bisdithioglyoxalnickel 3n Hy< ~ehydr and Realted Compounds, G.N'.Schrauzer and V.P_,Mayweg,..J. Am, CY.em.. Soc. 87, 3585 (1965) .. Cotial; 48. . Concerning the Synthesisof Dithio-a-diketoneCoa:plexesof Transition Metals ar,d A ;;indg. from Thiophosphates of1,2-Dithiols, G.N. Schraueer, V.P'. Mayweg and W. Heinrich, Inorganic Chemistry,4, 1615 (1965)... 53, S;.-nth 49. Electronic Transitions and Bonding inTetrakis(trifluorometh,yl)cyclopentadienone- s^.d' R ,. vclopentadienyl,,G:N. Schrauzer, Inorganic. Chemistry4,.2641(1965). cobalt C 5 . Jn CO 50. , The Crystal and Molecular Structure of MoS C6H6„ G.N. ScHrauzer,V.P. Mayxeg, Cbbam iird$ W`. Heinrich„ J. Am. Chem. Soc. 87, 5798 65:. -gan. 51. Uber Gobaloxime(II)und derenBeziehung zum~Vi'tamin B , Gerhard N. Schrauzer Schra 52. und'~Riehard J. Windgassen, Chemischc Berichte.99, 602~~~966). Elektronenstruktuur, Lichtabsorption und Reaktionen von Vitamin B , und seinenDerivaten, G.N. Schrau_er, Die ?iatur.+issenschasften 18,. 459 (196~J. On Tr 08 - i2h~Deiocalized Ground! States. Tris(dithioglyoxal)and oundsw Co i di 6'. The \ . mp r,at on 53.Coor Relatsd Prismatic a-Dithiodiketone.Complexes ofTransition~Metals', G."7l Schrauzerr and S':P. blar.:eg, J. Am. Chem,. Soc_. 88, 3235 (1966). 58 lri ndg i.on 54. Alkylcobaloximes andiTheirRe.lation to Alkylcob'alamirts, G.N. Sehrauzer and ?.11. R'.J. Windgassen, J. Am. Chem. Soc.,88,..3738'(d966). 6'3, CharF:. 55, Coordination Compounds with Delocalized Ground.Scates.. BisdithiodiketoneComolexes of Ironand Cobalt, G.N..Schrauzer, V.P_Mayaeg, H_W.Finck, and W. Heinrich, J.. Am. Chem. Soc.88„ 4604 (1966). 56. Polarographic Study.of Coordination Compoundswith Deloealized Ground States. 0. Diall Bis(c C`;er~. The. P Substituent Effectsin..Bis- and Trisdithiodiketone Complexes of Transition Metals, D.C. Olson, V.P,..Mayweg,.and G N. Schrauzer„ J.Am.,Chem. Soc. 88, 4876 (1966). 57. Pi-Complex?lulticenter Reactions Promoted byB'ihuclear Latalyst Systems.. "Binar-S"; aNew Heptacyclotetradecane via Stereoscecific Dimeri:ation of Sicycloheptadiene,. G.\. Schraucer, B.N. Bastian,.and G:A. Fosselius, J...am.,Chem. Soe. 88, 4890 (1966). Ezi& Lee :
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9 149 sl. Ccordination.Compounds wi2h.Delocalized Gcoun&States. a-Dithiodiketone- SWostituted; Group VI Metal Carbonyls and Related Compound5„ G.N. Schrauzer,. ;.P. >la.,eg,, and W. Heinrich„ J. Am., Chem. 5oc. 88, 5174I (11966):. 53:s-adducts of Group VIII Metal Bisdithiob'enziliCompiexeswith Phosphines, C.P. }lay°.eg and G.N. Schrauzer, The Chemical Society, ChemicaLCommunications, page 640. p;: "etallkomplexevon.a-Dithiodiketonen - ungewChnlicheChelate xit delokalisierten 4:Indtustknden, G.N. Schrauzer and V.P..Mayweg,"Nachrich't-en~ausChemie und''echnik" 24, 504. (1966). 61. On Hydroxyalkyltobaloximes and the Mechanism of a Cobamide-DependentDiol Ceh.drase, G.N. Schrauzerand R.J. Windgassen,.J.Am.Chem. Soc. 89, 143 (1967). 5:. Ccbalamin.Mode1 Compounds., Preparationand'Reactians of;Substituted.Alkyl- and Alkenvlcobaloximes.and Biochemical Implications,.G.N. Schrauzer.and R'.J. i+iadgassen, J..Am.,Chem. Soc. 89,.1999 (1967). e3'... 5'.-.t.4esisof Imethyl Groups Catalysed by Vitamin 8 in Vitroy G.N..Schrauzer ar.d R.J. Windgasseny Nature 214, No. 5087, 492(i1~~~) ~ e e 6 a+. :n Cabaloximeswitti.Cob'alt-Sulfur.Bonds and Some Mode1 Studies Related to 6obamide-Dependent Meth,vl-Group-TransferReactions,.GIN. Schrauzer.and R'.J. ciTdgassen, Js Am. Chem,.5oc. 89, 3607 (1967). 6i. Jrganocobalt Chemistryof.Vitamin B1~,Mod'e1 Compounds (Cobaloximes), G.Y.3ch'raueer, Account of Chemical Rese3cch, page 97 (1968), $6. 0:: T7ansition~Meta1-Catalyzed'Reactians of Norbornadiene.and the Concept ec - Cocpiex2lulticenter Processes,.G,N. Schrauzer,,Advances in Catalysis 10, 373 (1968)... 5'. The.\ucleophilicityofl Vitamin B12 , G.N: Schrauzer, E. Deutsc5,, and R'.J. '.;indgassen„ J. Am, Chem. Soc. 90, 441 (1968),. 5!. iron Carbonyl Complexes ofCyclooctatetraene Dimers, G.N. Schrauzer and 'J';'. Glackner, J. Am. Chem.. Soc. 90, 2800 (1968). =3!"-'~.arge Distribution and, Nueleophi4ic Reactivity in Sulfur Ligand Cheiates. Dialk.,l Derivatives of Nickeli(II)., Palladium(II)...and Rlatinum(SI) Bis(cis)ethylienedithiolates, G.N. Schrauzer and H.N:. Rabinowitz,J.Am. Che.: Soc. 90, 4297 (1968). -~TThe Reaction of Vitamin B1 and of Cobaloximes with Carbon Monoxide. Eridence fon Self'-Redu¢ti8naof Vitamin B in.Neutra3 Solution, Lian-Pin Lee and G.V..Schrauzer, J. Am. Chem.,Soc1250, S274 (1968). r M 0 I 0 0 0
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150 71. Methylcobalt Derivatives of Vitamin B1Q MbdhliCompounds asSub'stratesih Enzymatic Methane Formation, B.C. bteBride, J.M. Wood, J.W. Siber2, and G. N. Schrauzer; J..Am..Chem. Sbc.,90„ 5276 (1968). 72., The Molecular and Electronic Structure of Vitamin,B 2, Cobaloximes(II)i, and'Related'~Compeunds,.G.N. Schrauzer and Uian.Pin.~.ee,.J. Am. Ghem. Socs 90, 6541 (1968). 73: Photochemical and Thermal Cobalt-Carbor. Bond Cleavage.in Alkylcobalsnins and Related Organometailic Compounds. A Comparative Study, G.N: Schrauzer, JI.W. Sibert and R.J.Windgassen,.J...Am...Chem. Soc..90.,,6681 ('1968). 74. Coordination Compounds with Delocalized Ground States. The.Transition Metal Derivatives of Dithiodiketones and Ethylene(1,Z).dithiolates (Metal Di2fiienes):,,G.N. Sch'rauzer, Accounts of Chemical' Research, 72(i1969). 75. Electron Transfer Reactions Catalyzed byVitamin B12 and Related Compoundk: The Reduction,of Dyes and of RtiEoflav~im by Thiols,.G,N. Schrauzer and J.W... Sibert,. Biochemistry andBiophysics.130, 257 (1969). 76'.: Coordination Compounds of Unsaturated 1,Z-Dith'io1sand 1,2-Dithioketones, G.N. Sclirauzer, Transition Metal Chemistry 4„ 299 (1969), 77. Reactions of Cobalt.(t).Supernucleophiles. The AlErylationof.Vitamin B12s' Cobaloximes(I);,, and Related CompoundS,.G,N. Schrauzerand 6. Deutsch,. J. Am. Chem.,5oc. 91, 3341 (1969). „ 78. The Chemistry of Go(d) Derivatives of Vitamin B 2 and of ReiatedChelates„ G.YL Sehrauzer, Annals of.the.:~e~r York AcademyaF Sciences 158, 526'. (1969)I. 79: Semiconddretor Properties of T7ansition Metal Chelates ofLigands.Derivedfrom a-Dithiodiketnnes, E.Ji. Rosa and G'.V. Schrauzer,;J. of Physical Chemistry 73, 3132 (1969). 80. Methyl Derivatives of Tris(icis-stiLbenedithiolates)lof Tungsten and'Rhenium, G.Y: ScSrauzer, H.N. Rabinowits,. J..Am.,Chem. Soc... 91, 6522 (1969). 81. Organometallderivate desBis(dimethydglvoximato):-kobalts, Gerhard.N, Schrauzerund GUnter Kratel,.Ghemische Berichte 102, 2392 (1969). , 82. BisdimethyUglyoximatorhodium Derivatives. Analogs of Cobaloximes, J.H'. Weber, G.N... Schrauzer, J. Am: Chem. Sac. 92, 726 (1970). 83. Stabilization of a Thioketocarbene through e~Complex Formation. Synthesis and Structure of Trihav4o-1,2-diphenylthioketocarbene-Hexacarbonyldiiron,. G.tr. Schr,auear, H.`1: Rabinowitz, Je Ann K. Frank, Iain.C. Pau1,.J. Am,.Chem. Sac. 92', 212(19T0). 4
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151 84. >"ex. Catalysts of Stereospecific Norbornadi~ene Dimerization to."Sihor-S"' (1,2,4:5,6;8-Dinethenm-s-Indacene)„ G.N. Schrauzer, R.K.Y,. Ho:and Gl Schlksinger~„ Tetrahedron L'etters 8,, 5'43.(1970):. 85. Coec+-}me 61.2 and Coenzyme 812.Modei.Compoundsin the Catalysis ef'the Cehydration of Glycols„ G.N. Schrauzerand.J.W. Sibert, J. Am~. Chem. Soc.,92„ 1022 (1970). 86. Enz}aaticand'Nonenzymatic Demethy.latibn~of.Methy.lcobalamin~and of Abiogenic Cobaloxime Model Substrates. Methane Biosynthesis b'y.Methanobacillus omelianski~i, J,N..S'ibert and G.N. Schrauzer,.J. Ama Chem. Soc. 92, 1421 (1970). 87. Cobalo.ximes(II).and Vitamin B1.2r as Oxygen Carriers. Evidence for MUnomericand'Dimeric Peroxades and.Superoxides, G.N: Schrauzer, and Lian-Pin Lee, J. Am.. Chem. Soc..92„ 1551 (1970). 88. Chemical Evolution of a Nitrogenase Modei.: I. Reduction of Acetylene and Other Substrates by a Mol,vbdEnum-Thiall Catalyst System, G.N: Schrauzer, G. Schlesinger, J. Am, Chem. Soc. 92, 1808 (1970). 89. C?tar.iin B, G.N. Sch'rauzer, 1970iMeGraw-Hili Yearbook of Science and Technology2,385 (1970),.. 9- . Alkylcobalamins and Alkyicobaloximes. Electronic Structure, Spectra.,, and Mechanism of Photodealkylation,.I1.P. Leeand J.W: Sibert, G,N. Schrauzer, J. Am. Chem.,Soct 92, 2997 (1970). 91. Structure,. Alkylation, and Macrocyclic Derivatives.of Bicyclo.[2:2.1]hepta- _,5-diene.48ducts of Metal Dithienes, G.N::Schrauzer,. R'.K.Y. Ho6 R,P.. Murillo, J.:Am...Chem. Soc. 92,, 3508.(1970),. 92. Acetate Synthesis from Carbon Dioxide and Methylcorrinoids. Simulation.n of the Microbial Carbon DioxideFixation~Reaction in.aModel Systemy C,F. Schrauzer, J.W. Sibert, J. Am. Chem. Soc.:92,.3509(197.0). 93. Octahaotobic,vclo[4.2.2]dbca-2,4',7,9-tetraenediiron Hexacarbonyl. The. Siructareof the Reaction Product of Fe2(CO)g with Bullvalene,.G.Y. Schrauzer, P'. Glockner., Kenneth I.G. Reid, IainC. Paul, J'~ Am. Chem. Soc. 92, 4479 (1970). 91'• The Reduction ofVitami~n 612 by Carbon Monoxide, G.N.,Schrauzerand L.P: Lee„ Biochemistry and Bioph'ysics138„ 16(1970)... 95. r'ormation, Properties, and Structure.of Cation Radicals of cis-1,2-Ethylenedithiol5 in~the Oxidative Soivolysisof Metal Bis- and'Trisdithienes, G.N1 Schrau¢er, H.N.Rabinewitz„ J. Am. Chem. Soc. 92, 5769 (1970).. 96'. Cebalt-Carb'on Bond Cleavage in~Substituted Alkyleobalamins and Alkylcobaloximes. Evidence ford=0rbital Participation and Olefin n Complexes.ef Cobalt(I) Nucleopl¢iles,.Gerhard N. S¢hrauzer, James H. Weber, and Timothy.M6 Beekham,. J. Am. Chem, Soc. 92,7078(i19Y0), 0
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152 97,. SchweizerischeChemische Gesellschaft, G.N.Schrauzer, Chimia 24, 153 (1970). 98. Vitamin.812 and Vitamin 8 12 Model Compounds, LecturePape, produced by A.C.S,, .ii., UberdieKohlenoa . (1970). 27b, 577, 99. Chemical Evolution of a Nitrogenase Model. It. Holybdate-Cysteine and 1:.. 13tamin 100. Related Cataly,stsih the.Reduction of Acetylene to Olefins and Alkanes, G.N.Schrauzer and P. A. Doemenyy J. Am. Chem..Soc. 93, 1608 (1971). Chemical Evolution of a Nitrogenase Model.. IIS. The Reduction of I]3., G.N~.~~ Sch Pediatri: The Vita Nitrogen to.,lmmonia, G.N. Schrauzer, G. Schlesinger, P.A. Doemeny,.J.. Am..Chem. Soc. 931 1803 (1971). 5}-ndrome and G.N. 1101. Hydridocobaloximes„ G.N. Schrauzer and R.J. Holland J. Am. Chem.. Soc 93 11s., Vitamin , . . „ - 1505 (1971)1. 178. 51 102. The.Mechanism of Coenzyme B 2 Action~in Dioldehydrasa,..Gerhard N..Schrauzer, l 1:5. The Chem. 103, Robert J. Hollland„ Jane A..S eck, J. Am. Chem. Soc. 93, 1503 (197.1). A.lkyi Group Transfer from Cobalt to Mercury: The Reaction of Alkylcobalamins, G.ti. Seh Chem_ So .1likyicobaloximes and of Related;Compounds with MercurieAcetate, G.N. .._.. The Stru Schrauzer, James H. Weber, T.M. Beckham and! R.K.T. Ho, Tetrahedron Letters3;. 27S (1971). Complexe and G..V.. 736 C197. 104. Model Studies in.Nitrogen Fixation and Cobalamin Chemistry, G.N:.Sehrauzer, Advances in Chemistry.Series. 100,, 1J197.1L).. .... Reductiv, 105... 106., Hydridocobalamin.and a New Synchesis ofOrganocobait Derivatives.ofViRamin B!2, G.N...Schrauzer, R.J. Holland, J..Am. Chem. Soc..93„ 4060.(1971):. Interpretation of the Meth,vleneBlue Reduction Test of Human Plasma and the Compound: TransferTinothy,! Che:..istr 07. Possible Cancer Protecting Effect of Selenium, G.N: Schrauzer andW.J~ Rhead, Experientia 27, 1069 (1971). , Novel Degradation Reactions of Halomethyl Derivatives ofBis(diacetyldioximato).- 113. Coccernid Related I Intarmedi Soc. 95, cobalt, Gerhard N. Schrauzer„ Anthony Ribeiro, Lian-P. Lee and Raymond K.Y'. Ho, Ahgewandte.Chemie 10„ 807(1971). 119'. Recent Ac 108. Risks of Long-Term Ascorbic Acid Overdosage, W:J. Rhead and G.N. Schrauzer, Compound; Pure and 109. Nutrition Reviews 29„ 262 (11971). Recent Advances in the Chemtstry.of Transition.Metal.Complexesof Unsaturated; StabilizF Derivatih Bidentate Sulfur Donor Ligands (Metal Dithienes)~, G.NL Schrau¢er, Advances inChemistrySeries100,.73 (1972). 21. Horst Ki'a Selenium. 110. ChemieaL Evolution.of a Nitrogenase Model. IV.. Reduction ofLsoni'triles G.N... Scht , G.N.Schrauzer, P.A..Doemeny, G.1Y. Kiefer, and R.H..Frazier., J. Am..Chem. Soc. °94, 3604 (1972)., 329 (197, Dioldeh,vd. Oxide and Zeitschri
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153 111.. Uber die Methylenb'lau-Hemmung der Reduktion des.Hydro.xocobalamins durch Kohlenoxid, G.?f.Schrauzer and W.J..Michaely. Zeitschrift fUrNaturforschung 27b6 577(1972).. 112: 1'itamin.E, selenium, and the suddbn infant death syndrome, WiI'1iam,J. Rhead, G.\: Schrauzer, S.U.SaLtzstein„ Earle E. Cary, W:H. Allaway, Journal of Pediatrics 81, 2 (1972).11G, The Vitaminm.E and Selenium Status of Infants and the Sudden Infant Death Syndrome,.Wililiam.J. Rhead, Ear1b.E..Caryy W.H:Ailaway, S.L. Saltzstein and:G.N: Schrauzer, Bioinorganic ChemistryL., 289 (5972). 114. Vitamin,BL?,(Snorganic Chemi'atry.of Vitamin B12)„ G.N. Schrauzer, Science178', 51 (~1972)s 115. The Chemical Evolution o.f.a Nitrogenase Model. V. The Reduction of Nitriles, G.S. Schrauzer, P.A. Doemeny, R.H. Frazier, Jr.,, and G,W. Kiefer, J. Am. Chem, Soc. 94, 7378 (1972). 1!6. The Structure ofthe C1 H•Fe3(CO) Complex Derived from Iron.Tricarb'onyl Complexes of Dimers of ~y~¢o-oct~ate?raene, AndtewH:-d. Wang and lain C. Paul, and G.N. Schrauzer, Journal of the Chemical Society ChemiealCocununications,736(1972). 177. Reductive Dealkylation of Aikylcobaloximes, Alkylcotialamins, and Related Compounds: Simulation of Corrin,Dependbnt Reductase and Methyl Group Transfer Reactions„ Gerhard N-Schrauzer, Jane.A.Seck, Robert J..Holland, Timoth,vM. Beckham,.Edward M. Rubin, andJotin W. Sibert, Bioinorganic Cheeistry2,. 93. (1972)... 114. Concerning the Mechanism of.Action of Coenzyme B i2 in Dioldehydrase and Related Enzymes. Synthesis and Reactions ofPos~ulated Organocorrin Intermediates, G.N.,Schrauzer,.W.J. Mich'aely; R~J. Hollandy Ji. Am. Chem, Soc.95,,2024 (1973). 119. 12C. 122. Recent Advances in the Chemistry of Vitamin B and VitaminB Model Compounds: ReductiveCob'alt-Carbon B~ond:Cleavige Reactions, t;ZN.Schrauzer, Pure and Applied Chemistry 33, 545 (1973).Stabilization of1,3-Dipoles by m-Complex.Formation. Iron Carbonyl DeriM1•ativesofThio- and Selenoketocarbenes, GerhardN. Schrauzer and Horst Ki'sch,J. Am, Chem. Soc. 95, 2501(1973). Selenium and Cancer:Chemical Interpretation.of a Plasma "Cancer Test", G.N. Schrauzer, W.J..Rhead and G.A.,Evans, Bioinorganic.Chemistry 2, 329 (197.3)• - Dioldehydrase: New Observations Concerning the Effect of Oxygen, NitrousOxide.and Carbon Monoxide, G.N:SChrauzer, Jane A. Seck and R.J. Holland, Zeitachrift fUr Aaturforschung.28c„ 1 (1973):. . Im 0 I ®
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154 123.Aseorbic Acid Abuse: Effects of Long TermIngestion of Excessive Amounts on Blood Levels and Urinary Excretionj G.N. Schrauzer and 124. 125. 126. 127, . 128, 129. K.J. R:iead, International Journal for Vitamin~and Nutrition Research. 201 (1973). 45 , 167. . Chemical Evolution~of a Sitrogenasa Mbdel. VI... The Reduction of CY-„ S3, 520, NZ and Other SubstYatesby.NolybdocysteineCatalysts in.the PresenceoF~ Xucleosidb Phosphates, G.N. Schrauzer, C,W, Kiefer, P.A. Doemeny,.and Hl Kischy J, Am. Chem.5oc. 95, 5582 (1973). :3. Sudden,Death in Infancy and Vitamin E Deficiency, W.J. Rhead, G.N. Schrauzer and',S.L. Saltzstein„ British Medical Journal 4, 548 (1973)'... Reactions of Vinyl Ethers with Cobalamins and Cobaloximes, W.J. Michaely,.. .». ; G.V..Schrauzer„ J. Am, Chem. Soe. 95, 577.1(1973),. Reductive Co-C Bond Cleavage o_f.Alkylcorrins. and of Vitamin.Bl2 Model Compounds byAlkaliine C0,.5'Q , and'~Stannite„ GGN. Schrauzery,J..A. Seck and T.M. Beckham, Bioiaorganic'.Chemistry 2, 211 (1973). The Chemicai Evolution of'a NitrogenaseModei. VIL.The Reduction of S'itrogeny G.N..Schrauzer,,G.lr. Kiefer, K..Tano, and P.A.,Doemeny, J. Am. Chem, Soc., 96, 641 (1974)~. Selenium in,Human Plasma:: Cevels.in Blood:Proteins and Behavior upon. I Dialysis,. Acidification, and Reduction, W.J..Rhead,.G.A. Evans and G.V: Schrauzer, 8ioinorganic Chemistry 3, 217 (1974). 130. The Selenium Cataiy:ed'Reduction of Methylene Blue by Thiols, W.J.RheadandG.V: Schrauzer, Bioinorganic Chemistry3., 225(197.4), 131'. Inorganic Chemistry,,G,-N. Schrauzer (book review), in..Bioinorganic Chemistry 3,. 279 (1974)... 132. 133. 134. The Mechanism of BiologicallNitrogen Fixation: Recent Investigations of Model Systems, G.N: Schrauzer, P.A..Doemeny, G.W. Kiefer, H. Kisch and K. Tano,,Proceedings of the Climax First InternatiionalConference on the Chemistry and!Uses of }blybdenum, University of Readingy England,.Ed. Clietax.Molybd'enum Company;. Limited,Londbn,.1974, tdechani~smsofCorrih Dependent EnzymaticReacsions, G.N. Sehrauzer, Progress .5, in the Chemistry of Organir Natural Products.31, 583 (1974). Synthesis of Superconducti'ng.Compounds by ThermolysisofVolatile Hydrides and Organometallic Compounds on Glowing Wires, G.N. Sdtirauzer.and.H: Prakash, 147., Solid State Communications 14, 1259 (1974)i. 135. The Mechanismof Biological Nitrogen Fixation: Recent Investigations of; Model Systems, C.N. Schrauzer,.J.of the Less-Common Metals. 36, 475 (1974).
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155 156. Reactions of AlOrylcob'alamins andlof Related Complexess with Mercaptide Ions: S-Alkylation b'y, Nucl'eophilic Attack, G.N. Schrauzer and E. A. Stadlbauer,,Bioinorganic Chemi~stry:3, 353 (1974). 157. slethylcobal4min and Methylcobalt Complexes of Vitamin B Model Compounds as Substrates in Nucleophilic.Displacement Relctions, E.A. Stadlbauer, R.J'. Hoiland,.F.P. L'amm, and G.N. Schrauzer, Bioinorganic Chemistry.4, 67(197:4). 138. Effects of Selenium and of Arsenic on th'e. Genesisof Spontaneous Mammary Tumors in InbredC31<'Mice,Gerhard N:Schrauzer and',Debra Ishmael, Annals of Cii¢~icaiH and Laboratory Science,. 4,.. 441, (1974)I. 139. Sudden Infant Death Syndtome: Plasma Vitamin E Levels and Dietary Factors, G.N. Schraueer, Wi1liam~J. Rhead, and Sidney L. Saltzstein, Annals of'Clinical~ and. Laboratory Seience„ Voli. 5, No....1, 31 (1975). 140. Ethanolamihe Ahnmonia-Lyase: Inactivation of the HoloenzymesbyN20 an d' ~thed'~the Mechanism, ofActioro of Coen:ymeB 2.,. G.N.SChrauzer andE.A. Stadlbauer, Bioinorganic Chemistry; ~, 185 (,1975). 141. Neue Denkwege dbr Biochemie, Cerhard N. Sdirauzer„Bild; der_ Wissenschaft, 1925, pp. 82-86.. 142. Synthesisand'Electrical Properties of TransitionMetallMercaptides of 1,4-Dimereaptobenzene. G.NlSckirauzer and H.Prakash, Inorg. Chem. 14,, 12-00 (1975.)I. 143.. Nonenzymatic Simulation of Nitrogenase Reactions and the Mechanism of Biological Nitrogen.Fixation„ G.N. Schrauur., Angewandte Chemie, 14, 514 (19.75). 144. Chemical Evolution of a Nitrogenase Model.. VIII. Ferredoxin Model Compounds as Electron TransferCataly,sts and'Reducing Agents in~theSimulation of Nitrogenase andHydrogenase. Reactions, Kazuo Tano and G.N..Schrauzer„ J.A.C.S., 97; 5404 (1975).. 1451 Chemical Evolution of a Nitrogenase Model. IX. ConcernimgtheEffects of Adenosihe 5.'-Triphosphate and of Acids in the Model.System~. and the Adenosine 5'-Tiriphosphate Requirement of Nitrogenase, G.N. Schrauzer, G.W. Kiefer, K. Tano, and.P.R. Robinson, Ji.A.L.S.,,97„ 6088,(i1975). 146, SomeAspe.cts of.Current Vitamin C Usage: DiminishedHigh-Aititude. Resistance Folilowirtg Overdosage, G.N: Schrauzer, D. Ishmael, and G.W. Kiefer, AnnalisYew,York.A'cademyof Sciences, Vo, 258, p, 377.,, (1975):.. .-,... The Chemical Evolution of a NitrogenaseModel'.. R., Reduction of ' Coordinate&Cyanide.Ion..iit Cyano. Complexes of blo:ybdenum(IV)and Their Use as Catalysts for the Reduction ofbtolecular Nitrogen and of Other Substrates, G.YL Schrauzer, P.R. Robinson, E.L. Moorehead,.and T.}I. Vickrey,,J.A.C:S. 97, 7069 (1975). ® E I 0 0 a
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156 148.. Synthesis and Reacti'onsof Formylmethylcobalamih and of Related Compounds, Ti.!A. Vickrey„ R.N. Katz,, and GIV. Schrauzer, J.A.C.S. 97, 7248 (1975). 149., PhotochemicaliInduction,of Enzymatic Activity of a Carbocyclic Analog.of Coenzyme B12:A Contribution to the Elucidation of the Mechanism~of Action of CoenzymeB12, G:.N.,Schrauzer,,R: Nathan..Katz,.J.:Grate and'T..M. Vickrey,, Angewandte Chemie, 88, 186.01976). 150. Seleniumand Cancer: AReviev. G.N: Schrauzer,. Bioinorganic Chemistry5, 275 (1976)1. 151. Seleniumand Cancer, G.N. Schrauzer, Chemica Scripta. 1975, BA, 108, (Abstract). 152: The Chemical Evolution of aNitrogenaseMode.l. XI. Reduction of Molecular Nitrogen~in a Molybdocyanide Systems. G.N. Schrauzer,.P.R. Robinson,.E.L.. 4oorehead, and T.M. Vickrey> J.A.C.S. 98„ 2818 (1976)s - 153. Cancer MortalityCorrelation~Studies. I. Statistical Association Between Cancers at Anatomically.Unrelated Sites and Some Epidemiological Implications, G-Y. Schrauzer,Medical'Hypotheses., 2,,No.2,. 1976'. 1541.. Cancer SlortalityCorrel1zaion~Studies. II. Regional Associations of Mortalities with the Consumptions of Foods:and OtherCommodrities, Gerhard.N. Schrauzer, Medical Hypotheses, 2~ No. 2, 1976., . . 155. Hydr~ogen Evolving Systems_ I:. TheFormation,of H2 fromAqueous Suspensions of Fe(0H)12and'Reactions with, Reducib'le Substrates, Including Molecular Nitrogen, G.Y. Schrauzerr and T.D. Guth,.J. Amer. Chem.Soc. 98., 3508 (1976). 1~i6, New Developments ihthe Field of Vitamin Bi :Reactions ofithe Cobalt Atom in Corrins and in Vitamin B12.?lo.del Compoun7ds, G.N: Schrauzer, Angew. Chem, Int. Engl/Vo1..15, So.,7, 417(1976).157. Inhibition of the Genesis of5pontaneousMamnary TumorsinC3HMiee: Effects of Selenium and of Selenium-Antagonistic Elements and their Possible Ro1e in Human~Breast Cance.r, 6.N. Schrauter, D.A. White and C.J. Schneider, Bioinorganic .. Chemistry 6„ 26S (1976). 1>8. The ChenicalE'volution of a\iRrogenase Modp1..12. Stoichiometric Reduction of Acetylene and! of MolecularGitrogen by bimnonuclear Cyano Complexes of'. Oxomolybdate.(IV)~, E.L. Moorehead', P. R. Robinson, T:.M. Vickrey, and; G.N. Sehrauter, J. Amer.Chem. Soc. 98, 6555 (1976). 159. Detection of4',5'-Ahhydroadenosine as the Cleavage Product of Coenzyme B1z in Functional Holoenzymes, R.Y.Katz., T:.MI Vickrey,.and'G,N. Schrauzer.,. Angewandte Chemie 15.,,542(1976), ;c0. Th.eR. by Va J. ?.m :61i. 'tolyb in th De::i:e 1e... Biozo G.N. New.C Depen Intet ;,a. React of tt Proc. Clim;i Cer : Sbl and : 167. CanceDietc Bioic 105. Canc~ ' Selei Se1e+ BioV 15:9. Chen:. Ison: Cata B.J. J., A] :70. Phot, G,N. 34-121
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157 6 i .e 0A f. u2 n 1t0,. The Reduction of.Molecular Nitrogen, OrganicSubstrat'esan&of Protons byb'aradiua(II)„ S,I. Zones,.T.b[. Vickrey,.J:G.P:almer, an&G.N: Schrau=er, J. Amer. Chem. Soc. 98, 7289 (1976);. . 161. Molybdenum in Bi~ologiealiNitrogen~Fixation:,.G,N. Schraucer, 'Molybdenumm in the Environwent.'Vol..1. W.R.Chappell and K.K.Petersen Eds., Marcel Dekker, Ihe. New York, 243,(,1976). 162'. Biological.Nitrogen.Fixation. Using Simpler Chemistry to Study Enzymes. G V, Sehrauzer, Chemi'stry, 50, 13 (1977)i. 165. \ew.Developmentsin:theField of Vitamin B1 : Enzyaatic.ReactionsDe?endent upon Corrins and'Coenzyme 812„ G.~. Schrauzer, Angew, Chem. Internatl.,Ed.:Eng1. 16i 233 (1977). 16a'. Reaetibnsof Mononucliear Complexes of Oxomolybdate(SV)...etc.;.PART XIII of;the Series "The Chemical Evolution of~ aYitrogenase Model, G.N. Schrauzer, Proc. 2nd Internatl. Conf. on the.Chemistry'and Uses.of Molyb'denum.Climax Molybdenum Company„ London, 1976; p. 246. 155. The Chemical Evolution of a Nitrogenase Mode1i.XIV. Stoichiometric Reactions of Complexes of Molybdenum(S), Molybdenua.(SV),.and !fclybdenum(III) withAeety.leneand Nitrogen, P.R..Robinson, E.L. Moorehead, B.J..Weathers, E.A'. Ufkes„ T.M. Viek'reyand G.>f.Schsauzer, .I. A1ner.:Chem. Soc.:99,.3657(1977). 1s6. De.r 2-Chlorathoxy-carfiony.L-rest.Als:P-terminale, Mit Superaucleophi~len. SeQektiv.ibspalcbare.Schutzgruppe von Amihosauren, H.:Eckert, G.N. Sehiauzer, and I. Ugi,:Tetrahedron 311, 1399 (1975). . 16'. Cancer 4ortalityCorrelationStudies.Ill. Statistical Associations with Dietary Selenium Intakes, G.Y..Schrauzer, D.A. White and C.J. Schneid'er,. BicinorgantcChem; 7, 23 (1977). 1b5. Cancer \]ortalityCorre.Iat:~en~Stedies. IV: Associatiorswith Dietary, Selenium Intakes and B1ood Levels of Certain TraceEler..ents, Notably. Seleni= Antagonists, C.N. Schrauzcr, D.A. rihitzand C.J..:Schnei~der,. Bioinorg. Cbem, 7, 35 (1977). 169_ CrieaicalEvolution of a Yitroger.ase Model. X'1.Reduct:ion of Coordinated Isonitriles in.Nononuclear~ Complexes of OxomolytidareLIV)) and Their Use as, Catalysts for the Reduction of Acetylene and:Nitrogen, E.L. Moorehead, B.J.. lveat:iers, E.A.Ufkes. P.R.:Robinson, and G.N.Schrauzer, J. Amer,.Cltiem. Soc. 99, 6089 (1977). 170. Photolysis of Water and Photoreduction of Nitrogen on Titanium~Dioxide, G.N. Schrauzer and T.Di Guth, J..Amer. Chem~..Soc:. 99, 7189 (1977). 3.4-121 0 - 78 - l l e I
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158 The.fo,llowing statements are taken from a hearing by the Environmental Control Committee in, Chicagos Ilil., and arer~e.ferred to byMi+.. Jones on p. 75 Statement ofi Hiiam.ThomasLangston, M.D., Chicagos L11. I am Hiram Thomas Langston, a thoracic surgeon. I have practiced this specialty since 1941, and have been lbcated in the Chicago area since 1952. P am a clinical professor of surgery at the Northwestern.University Medical Schooll, and Chair- man of the Department of Surgery at St. Joseph Hospital here in Chicago. I am a Dipliomate of the American Board of Surgery, a Founder Member of the Board of Thoracic Surgery, a Fellow of the American Colilege of Chest Physicians, Past President of' the American Association for Thoracic Surgery„ and member of various national and local medical societies. Although my energies have been directed pri¢narily toward my medical practice, I have also published approximately 100 articlies anditextbook chapters - most of them,dealing with respiratory diseases, both neoplastic and non-neoplastic, and with thoracic surgery. Copies of my curriculum vitae and list of publications are attached. I have studied the relationship between smoking and health for many years and have recently also become interested in the so-callied "passive smoking"' issue. The current effort to restrict public smoking in Chicago is basedion the assertion that the health, as well as the comfort, of nonsmokers is jeopardized by exposure to tobacco smoke. Yet, there is no persuasive evidence that tobacco smoke harms,the nonsmoker. My :ence as a pt nature of c12ordinances ar In volume of wo, example, whe issue was su 1977. Durin he reported or plausible from passive K] Fi~sher,, for of' Pittsbur<, recently st 1 literature similar coi known prej
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11 159 My examination of the literature, as well as my exper- ,ence as a physician, has clearly demonstrated to me the tenuous ..cuse of claims regarding healith, hazards to nonsmokers, and of =i1inances and reguliations based on those claims. Interest in this area has resulted in a rather large r.:wne of work being carried out and reported from Germany, for c..:::ple, where the state of scientific knowledge regarding this :$nie was summarized by the German scientist Klost'erkotter in .f+7. During a conference on "'Passive Smoking at the Workplace," he repo:.ted that he had not "found any convincing facts, arguments :r plausible hypotheses supporting any probablie health hazards frcm passive smoking."1 Klosterkotter is not alone in this conclusion. Dr. Edwin R,. Iaher, for example, who is Professor of Pathology at the University :f Pi'ttsburgh and author of several hundred scientific publications, recently stated that: 11 the lack of'~ scientific information incriminating atmospheric tobacco smoke as a health hazard prompts me to concliude that proposals to place restrictions upon the use of tobacco in public places cannot be.justifi~ed on the basis of pathologilcc effects on or healith hazards to nonsmokers. As I have reviewedithe scientific and the popular literature,, I have been particularly impressed by the number of sinilar comments I have foundleven by individuals with well- known prejudices against tobacco smoking. For example, Dr. Reuel I E i 0 ® 0
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160 Stallbnes, an advisor for the 1964 report to the Surgeon General on smoking and health, was quoted as saying: In very direct terms there is no medical proof that nonsmokers exposedd to cigarette smoke in ordinary 5eLation with smokers suffer any damage. ' Dr. Ernst Wynder said in a published interview in 1i976 that Passive smoking,can provoke tears or can be otherwise disagreeable but it has no influence on the heal'th.4 In that case, the doses are too small. - Andimost recently, Dr. Michael J. Halberstam, senior editor of Modern Medicine, concurrediwith editorials publishe&in The Lancet andiNew England Journal of Medicine, which had concluded'that "there is no evidence of significant physical harm done to non- - smokers by smokers." Dr. Halberstam said "if we are to be scien- tific about smoking and if we are to take paranoia and pique out of the issue, we should also acknowledge the medical facts involved-- and to this date they indicate no physical danger to the nonsmoker."5 Much of the discussion regarding "passive smoking" focuses on carbon monoxide. Numerous experiments have attempted to assess the nonsmoker's exposure to tobacco smoke by measuring or calculating CO lievelis in various,situations, incliuding public transportation, offices, restaurants, etc. Many of these reports have exhibited an unfortunate tendency to equate levels of CO'. 41, ,i0 ,.,ith cigar only sourc ubiquitous t,ut also t externally CO,levels t:igher by were in tl moreclea_ comprehen T;gency pa ALi~terat(SOZ and such as p indoor pcoffices, that "Inc pollutiou the best lates an, be obtai of actua
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161 Q a Zt U r:7 .f q . '[9z> with cigarette smoking, as,if smoking were the prime and perhaps only source of CO in such closed spaces. In fact, however, CO is ubiquitous, andlindoor levels are affected not only by smoking, but also by cooking, heating, and especially by penetration of externalliy generated CO.6 Overall, tobacco smoke contribution to CO.L.evels is insignificant. In submarines, for example, CO concentrations were hiigher by, a factor of three in the reactor compartments than they were in the living areas where smoking was permiitted'.7 ' Studies of less exotic environments substantiate even more clearly smoking's relatively minor role. One of the most comprehensive of such studies is an Environmentali Protection Agency pamphlet titled indoor-Outdoor Air Polilutibn Relationships: A Literature Review. The authors reviewed information on gases (SO2,and CO2,, as well as CO), particulates, and viable particles such as pollen and bacteria. They examined all available data on indoor polSution in all sorts of structures--schools, hospitals, offices, public buildings, private homes, etc. They concluded that "Indoor air pollution is controlled primarily by outdoor pollution."' They also stated that "Under normal circumstances, the best available estimate for indoor concentrations of particu- lates and CO (and probably other nonreactive gases as well) can be obtained by presuming them equal to outdoor concentrations."6 If we put aside for the moment the important question of actual sources of COy we still find that the combined results ® I 3 N
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162 of studies on "passive smoking" using realistic conditions indi- cate that cO levels rarely exeeed 1i0 ppm.9-15 This is well' below the 50'ppm level' set by OSHA as the standard for daily industrial exposure over an 8-hour period. In-his summary of the proceedings of an international conference on Environmental Tobacco Smoke Effects on the Nonsmoker held'i:n Geneva in 1974, Dr. Ragnar Rylander discussed the significance of such CO Levelsc "Concentrations that are present under real- istic environmental conditions may reach about 10 ppm. . . It is true that higher concen- trations have been reported, but they represent only transient values or levels reached under experimental conditions . . . If the exposure to 10 ppm were to prevail for B hours the result- ing;COHb concentration would be1'.9% . . . . This value is well below the suggested WHO maximum of 4%. At these levels no adverse biological effects wi1L occur inia population that can be expectedito be present in such environments. It can thus be concluded'that the CO in environmental tobaccolisOmoke does not represent a heal~th hazard." Additional support for this position may be found in recent articles by Harke and Szadkowski, both of whom studied the effects of tobacco smoke on CO levels in the workplace. Harke, after measuring CO concentrations in office buildings, concluded that "No significant influence of smoking on the CO concentration seems to be present."17 Similarly, when Szadkowski observed nonsmoking workers' COHb levels during!the workday, he concluded that nonsmokers "were not subjected to any extra CO effects" from tobacco smoke.18' In fact, the Sza COHb levels actu to tobacco smoke Experi tobacco smoke he The relevance o: re.tes are smok questioned. In of such experim strong . .. . th expose themselN conditions."19 Deta: even under suclogicali effect After monitori ature, theres the most dramz caused a prec: such effect f. The smo cha eve cor .
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163 Detailed studies by Harkey et al.,ZO-ZZ emphasize that to ln fact, the Szadkowski article indicated that "passive smokers"" COHb levels actually declined after exposure throughout the day to tobacco smoke. Experiments reporting,"excessive" levels of CO from tobacco smoke have been conducted under highly artificial conditions. The relevance of these experiments, in which large numbers of ciga- rettes are smokediin closed and unventilatedirooms, must be seriously questioned. In 1975 Klosterkotter highlighted the basic fallacyy of such~experiments when he said "'the irritating effect becomes so strong. . . that even.indolent smokers would not voluntari~lyexpose themselves to such smoke concentrations under real life cond itiions.," 19 even und'er such severe test circumstances no evidence of a physio- liogical effect on the nonsmoker in a smoke-filled room is detectable. After monitoring EKG, blood pressure, pulse rate and skin temper- ature, the researchers determined that skin temperature showed the.most dramatic response to active smoking. Active smoking caused a precipitous drop in skin temperature, but there was no such effect from "passive smoking": on 0 9 I I The quantities,of smoke absorbed during passive smoking are too small to cause a significant change in the skin temperature of nonsmokers, even when the nonsmokers are located,in rooms containing extremely large smoke concentrations. I 0
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l 41 164 I might add that those experiments demonstrated a prompt +. fall in environmental levels of tobacco smoke components,, and CO . ~ ~?f in particular, when even Low,l'evel's of ventilation were provided. As long ago as 1955, Yaglou, Professor of Industrial `~ ~ Hygiene at Harvard School of Public Health, aliso noted the lack ~. of effect on the nonsmoker when he pointed out that "'the carbon .~ monoxide concentration was much too small to affect the nonsmoker, aJy: ~ even at the lowest air flow of 5 efmiper smoker, when the room ~ was fillied1with bluilsh smoke."15 , A few weeks ago I saw heavy'news coverage of an~article by Dr. Wilbert Aronow that was published in the New Engliand Journal €~ of Medicine.23 The article has been touted as evidence that nonsmokers in general, and'individuals with cardiovascular problems in particu- lar, are harmed by exposure to tobacco smoke. I believe, however, ~ that the article raises more questions than it answers. ra~ Dr. Aronow st'udied'ten angina patients, and the length 21 ~ .,~ of time between beginning of exercise and onset of' anginal pain~. ;f3# He reported that the interval was shortened by the patients' expo- sure to tobacco smoke. y Although I am not a cardiologist, I have read the art'iclie -, ~ and found several serious methodological flaws. The most important defect in the study involves the apparent totaL lack of control ~ over both the patients' and Dr. Aronow"s attitudes--a:flaw which L may have significantly affected the results of the experiment. The 4 article states that the patients received a"'careful explanation of the risks involved"' and that they "understood the experimental ~ design." Al' .ctroducing ,hat t he did e paroxysmal ic.pending des,:apect that ~-evelop anxi t.oo an agent l3gic effect Th iung disease -:ould! not, _:.•.ca 1 id ity, scoke in put these people certain adve nent, exerti Ir recent studi for the pref source of n: r„ight be af7, pesticides, ment of the accurate im, of' cigarett~
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J: ~M tj 165 design." A3thouqh Dr. Aronow states that he was careful to avoid! introducing "'psycholbgic factors," I suspect that that is preciseLy what he did succeed in introducing. The definition of angina is a paroxysmal thoracic pain, with a feeling of suffocation and impending death, precipitated by effort or excitement.- I strongly suspect that patients informed of "the risks involved" could easily develop anxiety-generated pain more qµickly when they are exposed to arn agent they, believe might harm them--independent of any physio- loaic effect from the agent itself. The question of protecting individuals with heart and lung diseases is a difficult one. Sympathy f'or their problems should not, however, obscure our recognition of the scientific v validity, based on current knowledge, of restricting tobacco s7ake in public places as a means of protecting them. In fact these people may have a far greater need for protection from certai'n,adverse weather conditions, general air pollution, excite- ment, exertion, etc. In addition to carbon monoxide and tobacco,smoke in general, recent studies have examined nicotine as a fairly reliable tracer for the presence of tobacco smoke--since tobacco is the sole source of nicotine. In special situations, experimental results might be affected by contamination from nicotine-containing pesticides, but this is probabliy unlikely. Therefore, measure- ment of the amount of nicotine in the air should provide a fairly accurate indication of the nonsmoker's exposure to the products of cigarette combustion, 0 I 8 I ~
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166 Although the technoliogy is still under study, exper- iments have been conducted to determine the concentration of nicotine in the environment, andito measure or calculate the amount of nicotine absorbed by the nonsmoker. Those studies, conducted in both experimental and actuali public situations„ have cliearly indicated that nonsmokers absorb only insignificant amounts of tobacco smoke.10,24-26 Hinds.and.First.,z6 from.the Hepartmentt of Environmental Health Sciences, Harvard School of Public Health and supported by the Massachusetts Lung Association, measured nicotine levels in several public pliaces, not just under experimental conditions. Huber, in an editorial comment27' on the paper by Hinds and First, has stated that their findings "demonstratethat in publ.icplaces nonsmokers could potentially consume 1/1000th to 1/100th of one filiter cigarette per hour, a level of exposure that has had no known serious associ- ation with d'isease."' There is no question that certain persons do not like tobacco smoke. In fact, an environment that is heavy with smoke produces annoyance and discomfort for smokers and.nonsmokers :+like. Such an environment, however, is rare, and when it does occur, com, mon sense dictates the necessary responses--including increased ventilation and decreased smoking. Tihe proposed regulation pertains far more to normal situations than it does to such rare occurrences. n .S hnd the ques emotional retihat actual Ir, re:;ponse may established al:ergic res leaf' extract s:roke. The Becker, at < producing aj~ however, ha;, andi Adams hand' whole s:M smoke may b psychoLogic to which va pollens, pe included in allergic re of concern regulation- tobacco sm emotional
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167 And the question therefore arises, why are we seeing such highly emotional responses, when scientific investigation clearly indicates thatl actual exposure is minimal. In rare instances it is possiblie that a truly allergic response may be exhibit'ed,, even though to date, it has not been established that tobacco smoke is capablie of producing a true allergic response. Standard allergy tests generalliy use tobacco leaf extract,, a.substance which may be very.different from tobacco s:noke. The few studies of actual tobacco smoke are inconclusive. Becker, et al. claim to have isolated a glycoprotein--capable of producing an allergic response--in tobacco smoke.ZB Gleich, however, has been unable to confirm those results,29 and Justus and Adamshaveconc.luded that water-soluble tobacco condensates and whole smoke db not produce sensitizat.ion.30: .. Most persons who say they are "allergic" to tobacco smoke may be exhibiting a sensitivity--whether of physiologic or psychologic origin. There are nearly unlimited numbers of substances to which various individuals may react, includimg,cat and dog dander,, pollens, perfumes, dusts, etc. Tobacco smoke may need to be included in this list, whether or not the reactions reflect true allergic responses. Although~the interestsofs such~people are of concern to all of us, they are hardly justification for sweeping regulation--whether it is designed to ban pets, or plants, or tobacco smoke, or other potentially annoying substances. Because scientific evidence fails to explain the extreme emotional reaction of a relative few nonsmokers when they are ® 0 ® I 8 ®
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168' exposed to tobacco smoke, we must look elsewhere for the explanation. Halberstam asserts that the symptoms exhibited by some nonsmokers "may'come from anger rather than from the smoke itseYf."5 A study conducted for western Airlines provides support for this theory of a psychological basis for the reaction. Robert J. Serling, the former.aviation editor of UPI~, wrote The Washington Post in 1977. He said: "'When pressure first arose to establish non- smoking areas on airliners, one carrier (West'ern)', went to Boeing and asked Boeing technicians to come up with the best means of achieving such segregation. Boeing's tests showed that the most effective way was to put smokers on one side of the aisle and non-smokers on the other--the ventilation system being such that it was virtually irsnpossible to smell tobacco smoke if the non-smoker was sitting on the other side of the aircraft. Western triedithis on one airplane--and was swamped! with complaints. It seems that all a non- smoker needed was to see someone smoking .. "I'm afraid this is just one more instance where emotionalism gets i~lthe way, of estab- lished scientific facts. Dr. Paul B. McCleave, while serving as a Director of the American Medical' Association, may have placed the matter in perspective when he wrote: z 4± 9 i c}ie smol becominc tory bo( :;ut by : the non eaists health m.andate ficatio
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169 0 Ck "As is always the case in any group that becomes anti of any situation or circumstance, there are always loud voices andimuch flag waving. So it is in the anti-smoking group. . . Smoking may be offensive to certain people but so is an alco- holic breath, a sweaty body, an unkempt figure,, a crying baby, or an undisciplined child ... if you ban smoking then will you bantqgse other annoyances.and inconveniences . . . ' . I urgee the: Committee to.adopt this reasoning and place the smoking issuein perspective. Tobacco smoking mayy befast tiec6ming the most popular "whipping boy" of our time, and regula- tcrl bodies must be swayed in this issue not by unfounded emotion, but byy scientific evidence. - An assertion that tobacco smoke is a health hazard to the normal nonsmoker is untenable. The weight of evidence as it efists in the world literature does not support a claim of adtrerse health effects for those exposed to "'passive smoking." The regulation of public smoking, under the guise of a m.andate to protect the public healith, is without scientific justi- fication. HiramiT.. Langston, M.D.~. ® 0 0 0 ® ©
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170 REFERENCES 1. Klosterkotter, W., "Passive Smoking at the Workplace," Bavarian Academy for Industrial antiSocial Medicine,. Munich,. Germany, March 31-April 1, 1977. , 2. Fisher, E.R.., Statement Before the New JerseyPubLic Health. Council, October 20, 1977. 3. Stallones, R., quoted in "Old Pete: He Smokes and'.Ilt's His Business," Reading Times,Reading,, Pennsylvania, September 17, 1976. 4. Wynder, E. L., "If You Smoke - Then Smoke Rather Harmless Cigarettes," Schweizer Illustrierte 25(10): 1, 1976. 5. Halberstamy M. J., "Smoking and the Nonsmoker," Modern Medicine, May 13, 1978. 6. Sterling,, T. D. and D. M. Kobayashi„ "Exposure to Pollutants in Enclosed 'Living Spaces,"' Environmental Research 13: 1-35, 1977. , 77. Ebersole, J. H.,. "The New Dimensions of Submarine Medicine," NEJM 262(12)': 599-610, March~24, 1960. 8. Benson, F. B., et al., Indoor-Outdoor Air Pollution Relation- ships: A Lilterature. Review,. U.S. Environmental Protection Agency, Publication No. AP-112,, Research Triangle Park, North Carolina, National Environmental Research Center, August, 1972. 9. Szadkowski, D., et ali., "Burden of Carbon Monoxide from Pas- sive Smoking iniOf'fices," Inn. Med. 3: 310-313', 1976. 10. Anderson, G. and'Ti. Dalhamn:, "The Risks to Health of Passive Smoking," Lakartidningen 70(33)c 2833-2836, 1973. 11. Cole, P. V., "Comparative Effects of Atmospheric Pollution and Cigarette Smoking on CarboxyhaemoglobiniLevel's in Man,"' Nature 255: 699-701, June 26, 1975. 12. Bridge, D. P. and. M.. Corn, "Contribution..to~the Assessment of Exposure of Nonsmokers to Air Pollution from.Cilgarette and Cigar Stmoke in Occupied Spaces," Environmental Research 5: 192-209, 1972. 13'.. U.S. Department of.Health, Education,, and Welfare, Health Aspects of Smoking in Transport Aircraft,, December, 1971. 14. Harke, H. gationso:f Int. Arch. 1i5. Yaglou, C. Trans.Ame 1955. 16. Rylander, Effects,"' Smoker, ed 17. Harke, H. : of Smoking Arbeitsmed 16. Szadkowski sive Smokii 1~. Klosterkot Arbeitsmedl 1975. 21j. Harke, H.1Smokiing„ _ 21. Harke, H. ]! Smoke Const'~ Function o7 Arbeitsmed. 22. Harke, H. I Inf'~luence cc mobiles," ] 23. Aronow,, W.~ NEJM; 2~99'~(1QI 24. Horning, E. Room~ Air," 25, Harke, H. I Mediziniscf 26. Hinds, W'. (~. Tobacco Smc 1975. 27. Huber, G. I NEJM 292(lE
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171 M 0 114. Harke, H. P., "The Probliem of Passive Smok,ing!. II. Investi- gati!ons of CO Level in the Automobile after Cigarette Smoking," Int. Arch. Arbeitsmed. 33: 207-220, 1974. 15. Yaglou, C. P.,,"'Ventilation Requirements for Cigarette Smoke," Trans. Amer. Soc. of Heating and Air-Cond. Engineers 61: 25-32, 1985. 16. Rylander, R., "Perspectives on Environmentali Tobacco Smoke Effects," in Environmental Tobacco Smoke Effects on the Non- Smoker, editediby R. Rylander, University of Geneva, 1974. 17, Harke,.H. P., "The Problem of Passive Smoking.. I.The Influence of Smoking on the CO Concentration in Office Rooms,"'Int. Arch. Arbeitsmed. 33: 199-204, 1974. 18. Szadkowski, D., et all., "Burden of Carbon Monoxi~def.rom.Pas- sive Smoking in Offices," Inn. Med. 3: 310'-313',, 1976. 19, Klosterkotter, W. and E. Gono, "Passive Smoking at Workplace," Arbeitsmedizin Sozialmedizin Praeventivmedizin 10(12): 233-236, 1975. 20. Harke, H. P. and A. Bleichert, "on the Problem of' Passive Smoking," Int. Arch. Arbeitsmed'. 29: 312-322, 1972'. 21. Harke, H.P.,, et al.., "PassiveSmokina;.. Concentration of Smoke Consti~tuentsin.theAir of Large andSma1S Rooms as a Function of Number of Ciggrettes.Smoked and Time," Int. Arch. Arbeitsmed. 29(4): 323-339, 1972. 22. Harke, H. P„et a:1.,."'The Problem.of Passive. Smoking. III..The Influence of Smoking onithe CO Concentration in Driving Auto- mobiles," Int. Arch. Arbeitsmed. 33: 221 229, 1974. 23. Aronow,W'. S., "Effect of PassiveSmoki~nl Angina. Pectoris," NEJM 299(1): 21-24',, Juliy 6,, 1978. 24. Horning, E. C.,, et a1., "Nicotine in Smokers,. Non-Smokers and. Room Air," Life Sciences 13: 1331 1346, 11973. 25. Harke, H. P., "The Problem of 'Passive Smoking:,'" Munchener Medizinische Wochenschri~ft (151) : 2328-2334, December 18, 1970i. 26. Hinds, W, C. and M. W. First, "Concentrations of Nicotine and Tobacco Smoke in Public Places,"' NEJM 292: 84i4-845, April 17„ 1975. 27. Huber, G. L., "Smoking and Nonsmokers--What i:s the Issue?," NEJM 292(116): 858-859, April 17, 1975. 11 0 0 0 a
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172 ~ 28. Becker, C. G. and T. Dubin, "Activation of Factor XI1I by Tobacco Glycoprotein," The Journal of Experimental Medicine 146: 457-467, 1977. 29. McDougall, J. C: and G. J. Gleich,, "Tobacco Allergy?," presented'at American Academy of Allergy Meeting, San Juan, Puerto Rico, 1976. 30. Justus,D. E. and D. A'.. Adams,"Evaluation of Tobacco Hyper- sensitivity Responses in the Mouse," Int. Archs. Allergy AppL. Immun. 51: 687-695, 1976. 311. Serling,. R. J.,"'Smoking on Airplanes," The Washington Post, p. A-16, July 7, 1977. 32. McCleave„ P. B„ "Where Do.You, Stop?,"'Wall'. Street Journall, p. 16, February 118, 11970. y F] F_eceof Bir'.h: Aio :a..eof Bi~r'-}i: Jar•t(C:f . t`;ez's Name: Alve 6ame: LomiI?-tion:. lToll; Ge~r Unis. Ur.i, Uni, ied: Helc e o-` Y.a:.riaoe:. Junc Cr.::aren: Pa•,:li Tho~ Qarc Bc- of U.S. parents. Ccr.vention.Educatec se=uer.t education as n i,y and Alptia Omega Y;er.rial F.ospital, s;a Y;ecorizl Bospital, 1'-7.-..:.Arhor,. 1!ichiaan, M_ctican, 1938.40; Ir Y.i:c.,igany 194D~41; Pzn szty, Cnicago, I11inc vice, Northwestern Ur J.fr:caand Ita1yy as C ly,avarded Army Co~ t?co.(D_ficer Gr,ade) v='-i, rank.of Assistar -oracic Snrge.ryy in I at Wayne University. 1.Associate Profess. 2. Chief Surgeon,.CFaea7th,.5tate of 211i Veterans A'•.srdnis.trati xug~stana (to 1971), a:=ycintedClinncal Pr cfMeCieint - 1962 ar „civersity of I11iinoi' (5<neral)AbrahamLir =_tencingThoracioS't %ro:esscrr ofSurgery,. 34-L21 0 - 78 - 12
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173 BIO,`,RAPHI:iL DATA: HIR.F`: :riC=AS :L'+LSIGN, Y..D~ S.ace of Birth:Rio. de Janeiro, Rrazil. ~ate o='Birtlic January12, 1912 (U:S.As Citizen by, Derivative Citizenship) '. • let`,er's Name: tto?-'s Naa,e: Alva B. Langston Louise Foe Diug•aid , C~~-a tion: Collegio Batista, Rio de Janeiro, Bcazil.,.to1928 Georgetovn College, Kentucky1929Ur:iversityof Louisville, l:entuckyy, 1929-30, A.B. UniversityofLouisvilSe, %entucky, 1930-34y x.D. Uni'versityof'Nichigen,. Graduate Sciool, 1939-41, H,S. ltarriec: Late. c. rir:.age: C^:::cran: HelenHl Orth - June 2]S 1941 Paula F. Ianastom, born June15, 1946Thomas O. LangSton~ born.Sep.tecber 5, 1949' Carol E. iangston, born5epter~ber 4,.1953 (Surgery) BRSEFCAR?~.ER. S'J`i'J,RY Doa: of U.S. parents engaged'in educaeional missions under theSouthern Baptist. Coa-ntion. Educated through.sopho:noreh year of colQege.in Rio de.Janeiro,, sub- se=uent education as outlined above. Elected to Theta Kappa Psi medical frater- r.ity, and A1pLa Omeqa Alpha honorary'medical.fraternity. Inte.rns:.ip: Garfieldeen_rialHospital,,uashington, D.C., 1934-35; Resident in Pathology, Garfield. eecorial Hospital, 1935-377 Assistant ResiSent in Surgery,,,UniversityHospital, Arm Ar3or,Y.ichigan„ 1937,38;. Resident in.Surgery, UniversityHospitai, Ann.Arbor,. kictigan, 1938-40; Instructor in Thoracic Surgery.,.UniversityRospital, Ann Arbor, KSchigany 1940-41; Private Practice aad Associate in Sur9ery; Northvesterr. Univer- aity, Chicago, Illinois, 1941-42; February.1942 to Febzvary.,,1946,.xiluta_ry,Ser- oioe, Northwestern Universitysponscred hospital (12-th. General)... Served in North A!rica and Italy as Chief ofThoracic Surgery. Rose torarilc of major, AUS; ultiaate- ly, avardedArarvCoim+.endation Ribbon~ Bronze.5tarHeda1 and Ordea do Atenito Aeroaau- ticc (Of.ficer Grade) (Brazilian Air Force). Aeturned.t-HorthvesternUniversityv!t`: rank of Assistant Professor of Surgery. In 1949 entered-rivate practice.of 7noracic Surgery in Detroit, Hichigar,~ and served as.Associate Professor of Surgery, ae sayne University.. Returned to:Chicago in 1952viih A?pointments as fol'lovs:1. Associ'eteProfessor of5urg.ery at UniversityofIlliinois. College o`f rie?icine. 2. Chief Surgeon,.Chioago StateTuberculosisSanittrium,.Depar=ent of.Public L,ealth, State of ISlinois. 1952-71. 3. Consultant im.Thoracic Surge:y, tothePeterans Adrihis.tration Hospital,Hines,Illinois. (1974) '. On the staff of au~-atana(to.1971) , Gottleib, Grant and Saint. Josep'; Hospitals. x?PC.inted Clinical Professor of e•.ss gery at the taiversityof Illinois, College c' nedicine - 1962 and,Professor of Surgery..,?.brahar.Lincoln~School~ of dYedicine, ':-.ivezsity of Illinois, 1973 to 1977 - Served'as Chief o`.T'noracic Surcery' IGrnezal)I Abraha~ Lincoln School of Hedicine, U1.iversityofIllinois, 1973 - 1°.75... A'te=_ineSuioracic Surgeon - Cook County. Hos_itall 1966 - 1977, Appointed Clinical~ 7cc:essv- of Surgery,.NortS:vestern Universitv Ysdical Scnool- 1976: 34-124 0-78-L2 Q1 I M
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174 Biographical Data of Hiram Thomas Langston,.M.Da - 2 -PRIt:CIPAL PROFESSIO.'V..'. OR BUSILSSACTIVITgS Diplomate, American,Board of Surgery, 1942 - Founder MesSer, Board of Thoracic Surgery, 1946 - Member, The Board'ofTnoracic Surge_ry> 1956-1961 - MeaDer of vari- ous comitteesof national and local societies - Secretary, American Association for Thoracic Surgery, 1956-1961 - Vice-President, American Association..for Thoracic Surgery, 1968-1969 - President, AmericanAssociation forThoracic5urgery, 1969- 1970 - Chicago Surgical Society - Vice President 1971-1972. - Pre.sident Jo`m Alexander Society, 1977. Chairman~ Department.ofSurgery„ Saint Joseph Hospital 1977 ` to present. Member,Editorial Board~of the John. Alexander Series, Charles C T.homas,. Publisher - 1973;, Member, Editorial Bm rd, Journal of.Thoracic and Cardiovascular Surgeryc Member,.ResidencyReviewCorar,ittee - Thoracic Surgery - RepresenGing:Aaerican . College Ssrgeons,.1967-72;. Cnairman.1969-72. vice President Staff Grant Hospital, 1972 to 1975; .Member,.Board of DirectorsG7ant Hospital,. 1973-1975. Thoracic Surgery.Representative,InterspecialtyCouncil AMA, 1979-1976 - NationalThoracic Surgery.,Manpo.!er Study - Executive Cocmmittee, 1971-1973. University ofIllinoisDistinguished.Serv.ice A.+ard„ June. 1975. (Department of Surgery) Me..~bership inMedicaL Societies. American College surgeons American Association forTnoracic Surgery American College of Chest Ph.ysioians (Fellov). American Medical Association American Surgical Association Chicago MedicaL SocietyQiicago Surgical Society IllinoisMedical.SocietyIllinoisSurgical Society The Institute ofMedicineof Chicago Pan-Pacific Surgical Association Society of Thoracic Surgeons Westera Surgical Association Societe Internationale de Q:irurgie American Thoracic Society Illinois Thoracic Soeiet}, Home A,3dress Professional
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17'5 K yyc..a_:ical Data of Hii&, Thomas LanSSton,.MLD.,- _ Membershipon F.ospital StaffsC1i~icaL Professor of Surgery, Universityy of I1linoisCollege ofMedicine - 1952-1978 Chief of Surgery,. Cnicago State Tubercu3osis Saniterium, bepartment of PuDliic Health,1952-1971„ State of, IllinoisConsultent in Thoracic Surgery, VeteransAdir.inistration Hospital, Hines.,Illiinois - 1952-1974 Attending Physician in Thor~acic Surgery, Cook County Hospital- 1970-1977. Grant.Hospital Henrotin Hospital - Resigned 1973 Aug-ustana Hospital - Resigned.197k Lake Forest Hospitial . St. Joseph Hospital .. ° Highland Park Hospital - Resigned 1971 Consultant in T'horacic Surgery - Presbyterian St. Luke's Hospital Lecturer - Abrah-Linroln College of Medicine- University.ofIllinois. Visiting Professorships Mayo Clinic Rochester - Sept. 27-29,,1966 Universityof Missouri'-Columbia - Feb. B-9, 1971 Universiky of Florida-Gainsville - Sept. 22-24,. 1971, Universi'2yof Michigan-Ann Arbor - May 16-18', 1973 L±: Hoae Address: 952 Pine Tree Lane, Winnetka,Illinois 60093 Professional or HusinessAddress: 2913.North C-ealth Avenue Chicago, I1linois 60657 I R ® ® ®
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176 Ym= CC?Y BIBLIOG?PFHY OF EIItA:1.. 1;1:GS'lO.i„ F;.D. 1. The Problea o: Catbst Sensitivit'y.rad its Relatioa to Rouzd Eeelin,-; AnralsoY Surgery,115,121-147,. Jas.ie-,y, 10:2: 2. Empye.:.ay Abstract in Qae_-terly 8.,lletin of Indiana UaiversityMedlcal Center, Ibdiana?o1is, Indiana, 4: October, 1942. _ 3. Tne Treatyent ofIntrathoracic ttounds; vith Wiliam M. RUtt1e,.M.D:.and Robert T. Crowley; M.D.; Abst:actia the b:edical Dulletin~.ofthe Nediterrrnean 15eater of Operations, 2: 142-149„ December, 1944. ^ibliop _cyc ?zfle 2 13. $eni&z E ZYan As so 14. 'lne Use ~ vith N.D. 15. . priz:a-'y. i vith Jera 16. Taoracic. Qu~ 24: , 4. The Treatneat,of Intrathoracio Wounds; vith Stilliem N: Tuttle, M.D. and~Robert T. Crovley,.M.D.; Sargeryp . Gynecology.&Obstetrics,,81: 158116a, Aigsst',.1945. 5. Tbe PatSology of ChronicTrau.:aticHenothorax; with W.illiam M. Tlsttle, M.Di;Journalof T:corecicShrgery.,.16: 59=11fi, Apri1, 1947• 6. 7• 12. 17. Esop1a€e= vith SurgE la. Benign EzA Col Gynec The Treataentof Or€a.nizisg Semotboraxby PalzoraryDeoortication; vith Ail11ez M..TUttle, Y..D.;. Journal of Thoracle. Surgery,. 16: 117-126, April" 1947' 19, The PerivN vith June, LungMobilization - Its Indications in the Y-~~enent.of the "Captiwe" Lung; Sargery,:'Gynecology&0'ostetiics,85: 301-307, Septe+=ber, 1947,• 2-'j, Intrathor Ianie Carie Pleuo-pul.monarry. Manifestations of Anzbissis;vith R. T. Fox, M.D.; Archives of S1:rger-y, 55:'618, fiovember, 1947. The Indication for Posterior Tre.nspleural Sronchotony intheY:a=s.geaent of Intrabronchial Tumors; - vith R'. T. Fox, M.D.; SUrgery,Gynecolog;/ & Obstetrlcs, 86: 1g2-196y February.,.1948. Intrabronchial Fibrcca Managed by Posterior Transpleural Dr.onctcafory;. 21, Rounded I with of Ra hoves SlirgeryoCGapt H.B. vi'tb~.R. T. Fox, M.D.; The Proceed3ngsoft,he Institvteof Medic:ne ofGGicago, 6icago Surgical Societyy 17: 53,Februery.15, 1$48. J. R. T eat Non-neoplastir.T%sefaction~of Rib - Renortof a Case; vith Edvard, Bi'gg, M.D.; @uarterlyBallean~of 1:o.Jlivestern University. Medi'cal ScLool'of Caicago, 22: 56-5g;. S?r 1-"-€ c,ur•,.e:., 1948. 23.. 24. The r vith Marcb Tbe DiaEP Tee Present'Status cf PulnonaryIkcorticatics;, Editorial in Shrgery,.G',{necolek~, & Obstetrics, 87: k78-L80, October, with Msrc3 1948:
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Eitliop phy.ofEirey T. Langston, M.D. ?abe 2 177 13. Besigz Endo3romchial Tumors; - - Transactions..ofthe 45;.GiAnnual Meetii:g o_t1e Nztionel T'uberctLosisAssociation,1949 . , 14.Tbe Use of Interstitial Radon.Seedse=3 Eeecles in Znoperable Lung Cancer; . . vitSZrving M. Ariel, M.D., Jerce R.. Eead,..{.D. end Edwa.-dE.Ave_ryy M.D.; Cancer,.2: 531-586, July, 1949..- . 15• P'ir,esyOarcin¢maof the Lung: A Clisical Study of1205 Cases; vith L^ring D:. Ariel, M.D., Edvar3 E.. Avery, M.D., L. Kantor, l:.D: tnd Jerme R. Bead, M.D.; Cancer, 3: 22~:-239, 7•arch, 1950. 16.. Thoracic StL geryin,the 12th General Eospital (U.S.),;. Qs..^tzrlyBulletin of Northvestern University Medical Scbool ofChicago,, 24: 210-221,.Fh11 Quarter, 1950i . 17- Esoi Duplications; vith Wi11ipm M. Tuttle., M.D:. and T. B. Patton, M.D., Archisesof Sugery, 61: 949-956, November, 1950. 13: Benign Eadobronehia,l Tumors; ACollecti4eReviev„ International Abstracts of Surgery in Surgery, 6ynecology, & .Obstetrics,. 91: 521-535, December, 1950. 19. ThePerivascular Space of the Puleonar3Vesselse AniAnatcmicDemocstrztion; vit2 A1Sred;M: Tocker, M.D.; TheJaurnaliof inoracieSurgery,,.23:.539-545,. June, 1952. . 20. Intrathoracic Surgical Procedures in Patients Past the Age of 60;.vith Daaiel C. Cezpbe11, Jr., Ma,jor.,. USAF(Y.C)g Joi the Americe•n Geriatrics Society, 3= 330-336, May, 1955• 2/. Rounded.Zntrathoracic Lesions.;; vit5 Donald W. Springer, M.D.; Paul E. Geiger., M.D:;The.Americe= Jotrnt+1 ofRoec`,.Renology, Redium Therapy.and Nucle:e.r Med;ciae, 74,5; e27-849, November1955. ~22. Surgery of the Chest; Cbapter No. 7'in "The RecoveryRoon - I~ediete Postoperative N.&nabement", W.B. Saun3ers Co.,. Pniladelphla &.London, 1956; Edited:byM. S..SZdove & J. E. Cross. 1ist.Editiom .. 23. The Treatmentof MetastatiePulmoRazyMalignancy;. vith Charles R. Aelly„ M:D.; The Journal of Thoracic Sw.:gery 31: March, 1956. 24. The Diagnosis of Pulmona•.ryLesions; . 2,a.°-315, vithNoble 0. Correll, Jr., M'.D..;,7Ilinois Medi'cal Jonnnal, 109: 117-119, March, 1956. 0 e 0 0 91
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178 Bibliogra_:.y of Eiie:-• T. Langston, M.D. Page I 25. An Aaalysisof the Late Results ofT'Loracoabdocin2l Wv.nnding;: : vittiAillie= M: TNttle„ M.D. and Robert T.Grovley, M'.D:;Aaerican Journa.1 of Su•geryy 91': . 578-58J,Apra, 1956, - 26.. Polyo.oidEndobronohSe1 ltmors; vi2h, Richarx' C. Povers,, M.D. and Melvi.nC.Godviny PnsD~ & M.D.; Archives of Surgery, 72: 984-990, J•,ine, 1956. 27.'lhe Cardiorespiratory Dynrlaics of Controlled Respiration in the Openen3 Closed Chest; with facHerS. Gordoa, M.D,.,, Fa.D. (By.7nvitat.ion);CcarlesS7..Frye, M.S. (By Invitation); Journal ofThoraeic Sargery, 32: k31-453, Oetober.,.1956. 28. ooK 29. Protective Mecbrsisns of the iYaobeobronchial Tree;; with Nobel 0.. Correll,, Jr., M.Di, ClinicalMedi'cine, 1i:61i,. January,. 19571. The Surgical 7reatmentof Pleural Tuberculosis;: Chapter VIII in the "Svrg'ical Maoagement of PolmonaryTubercvlosis"; with Noble 0..Correll, Jr., M.D:; Charles C. ^'J~oms - Publisber, Springfdeld,. I1linois 1957;.EdSted~J.D. Steele..lstEdiition ')DK30. The Postoperative Chest - Radiographic Considerations Foilowing Tnoracic Surgery; with Anton~M. Pantone, M.D. and N.yron Meia:r_d, M,D.; John Alexander Monograph Series - No. 2,.Charles C. Tnos2s - Publisher, Spriagfield, - Illinois, 1957. 1stEdition Pu].ronary LycpbatdcDrainage in the Dog: with Noble 0. Correll, Jr., M.D.; Surgery, Gyxecology.& Obstetrics, 107: 234-286y September, 1958. 32. The Surgery of Pulmonary T~berculosis; Presented at tLeForty-third Amnual Meeting of the Radiologicali Soclety of North Amer.ica, Cnieago:,,Il7inois, Noveober 20, 1957:;, p'ablis5ed in Radiology,.71: 345-34'7, Septeaber,.1953.33. Pleuropneumomeetoqy.in.Tuberculosi's; with Frank J. M.i]1oy,.Jr..,M:D.; Dlsease oftbe Chest, 34c 593, Dece.:ber, 1958. 34. 35. The 7ncidenceof Blood Vessel~ Inyasion in BroncLogenic Cercinoma;, with John F. Lavs, M.D., Elizabeth A. McCrev,,M.D:.;.ClarenmeBeidenreicL, M.D. andMir7i D.. Slc®inski,,M.D.; Slirgery,,GyvecoLogy&Obste:.rics, 107: 704-708, December, 1958. Sugeryof Pulmonsry. Rliberovlosis; Editorial in the Illinois Medical Jou-^nr1i,.114: 293-294,De.ceaber,,1958 36. Biopsy Procedures in the Diagnosis of Pulmonary Disease; The Medical Clioics of Nort3 Anerica, 43c 2^y1-296„ W. B. SaundersCo., January, 1959. -- Also spani3h ?'dition.. Bib1i oEr apn7 Y Ee k 37. persi A 3B: The B V J 39. Scace Pre-. v T 40. Pneuz . V J ~ 41. Ch-_ Dise_ z ~ F '~ ~ 42.. SargE ~ E ; 43. InJu: t )0;r, 44. . Tbe I i 45. Medi z 'r -L 46. Ful.n t3 47. SurE 48. Bile uh,r(
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Bibliog:aphy of Eirz:. T. Iangstony M.D. pEek 37. 179 Persistent Subarachn.oid-PlenralSpece Fiss••„1e: A.Czse Report.;; vdtS~Frack J. Mi11oy, M.D.. and 7:o_le 0. Cor-el2, M.D.; Journnl oftSe American Medical Association,.l69: 1»67, Ha-ca, 1959• 38.. The Bacterial Flora of the Bn:..an i7ac`_eo:rcnc:.izl T'ree; with Nrob1e.0. Correll, Jr., M.D:,.3r.1?h E. Eubble; Fn.D: eod Kecme:~~C.. Jo'nnstoa,MLD..;, The Journal of inoracic 5-.argery,.37: 3d7-373y.N-_rcz, 1553• 39. SgaceProbler.sin.Extensive. Resectionfor Pulmenary Tabercu,losis: The Use of Pre-resection 7"ailoring Thorecoplasty; with Fre-k J. Milloy,.M'.D. ar:d Ahsedi 1Ce.a.he: , M.D..;TLe Journal ofThoracic Surge.y,, 37: 1+42-4k5,Aprili„ 1959• 40. Pneumonectomyin theNazatement of Pu!no~ry Tubercnlosls;; vit':~F:~e.nk J. M:11oy,. M.D:;' Sugery,, Gynecolog-j& Obstetrics, 110;. 658-65L, June, 1960• 411. . Ch~otherapyy in Resection fo- Pu].:soy-ryTuberc•.:iosi':,: Problecsof Extensive Disease and D-ug-Resi6t&mt Organis_s; vith Marjorie M. Pyle, M.D. and Kz^l B..Pfuetz, M.Di;American Revievof RespiratoryDi~sease,.82: 51-58, July, 1960, 42: Surgeryih the Treatoent of PuleonaryTaberculosis; vith Joha. W. Broubard,.M.D. andFxRr.Y.. J.M31Soyy. M.D.;A.^chives of Sugery, 81: 269r27k,.August, 1960.. • J,K. 43- InJuriesof the Chest;, . Chapter inbook, "First Aid", 5th Edition,,eflited byNarren B. Cole, T:.D., Charles B. Puestov,,M.D.; Appletoe-Centv:yoroft., Inc6 Publishers, New Yorky N'...Y.;.1960. JCK 44. The Surgical Treat-ent: of Metast,zses to the.L.uig; - Chapter No. 24 in"TkieTreat.:.ent of Cancer and A111ed Diseases:",. A Coxprebensive Treati'se, 2nd Edition; L; 413-k23;.edit,ed~by C. T. Pack„ M.D. and I. M1 A:iely.M:D., Paul B.Boeber, Ihc., Publishers, Nev.York, N...Y.,. 1960. 1;5. Mediastinal Tumorsand~Cy.stsim theA&alt;- vithJoancides, M- Diseases of t3e Chest, 38: 243, . September, 1950. 7Ji.£ 46. Pul.nonaryTuber.culosls;, . - Cbapter No. 7iin."Ssrgi'cal Diseases of the Caest"', edited byBrian Blsdes,. M.D. with William M. Z1:ttle,. M.D:; C: V. McsbyCo., St. Louis, Mo., Publlsher,.January,.1961. 1sU Edition~ 47. Surgery of the Bronc3us.;The Uestern Journal of Sarge.ry.,, obstetrics & G?-cology, 69:.2`-'S-252,~ Ju3y-Aiigust,.1961. 48. Bilateral Si.mulca.neous BronchoEenic.Ct Repor~ o.'a Case Treated Surgicall.,y;; vithJcseob C. Sberrick,,M.D.; Jc~=z e..'rnorecic acd Car.iovasc::er S:L„er;•; L3: 742-7j1, June, '-p62. 0 0 E 0 FE
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180 . bibaiograp~y of EiramT:.Langstca,.M.D:Page 5 :_ol r ge "6z ~'9.. Pu:SO.^.a..ry:1:berct:Losis Lobecto=; &naoo_tysis} - . edited~by,NillSan~J. Donnclly:,MID., Caief,.Section ofRer..atoloz-y; P=nor't froc the C1inlcopathologleCo._fer:ence, Veterans A'fl`.^.lstration Hospi;zl, Hines, Il11noi's; Postgradvate Medicine, 32: 287, Sept'ecber,.1962. ' ;~K~ 62. 50. Patterns of Bronc5le-1i Arborizati on~in :he Lef:t Upaer Lobe: A Revieuof50J. ... Broacbograpbio St:'Jdies; with AnnStitt, M.D. and Fremk J..?a]loyy M.D.; Gue.-terly Bulleti:- of Norttvestern Medics4 SaboolofChlaago,.36:253, Fal1 Q;iarter,.19c2. 51. EXperiencesvith Autotransitssions; ' 63. vi'th~.Ceorge Talles, M.D. and W1l2iea Ielessandro, M.D.; Su.-gery, Cyn_cology. &Obstetrics,.115: 689-694,.Decesber, 1962. ' 6k. 52. Pre-resect3baRadiat ion~f~or Bronohogenic Carcinoca;; with L. Renfield Faber,.M:D. aad George D. Faiser, M.D:;.The Jou_^nal of '1'noracieandCardio%ascwlar S•ar5ery, 46: 227-231, AL:gnst,.1963. 53• FurtherExperiences vitb Aatogenous B1oodTrzmsfusions.p. 65 with GeorgeY..]1es, M.D. and Willia;Delessa=d:o, M.D.;presen`..ed before . the Aterican Surgical Associati'on, Ptioeclx, Arizona, AFril 3-5, 1c,1a3;; oubli~shed in Annals of Surgery,.156:'.333-337; SeP tember,1963. 6fi. ;OOK54.The Thorax, Pleura and Lungs: - Caapter 13 in Ch=iston3er'sTer.tbook ofSur.:ervy 8th Edition, Loya1 Dav1s,. M.D.. (ed),;Fniladelpnia: N. B..Savaders ooW a=y, 19`t'-,.Pp• 389-430. .. iL iv A t 67. 55. u otrans s n; with GeorgeMiSles, M.D.; The ModernHospit'al, 102:104, Diy, 1964. 56. Tracheostory.aad Assisted Ventilation: Use in Res.i:-atoryInsuffitiency in, . 58 •~ the Postsurgieal Patient; ' . vith A: E. Neville,.M:D..,.A. SpinazzoLa, M:D. andZ. P. Sciochihzmo, l.D:.,. Presented at tbe CentralSurgical Association Meeting,.Ro^bester, Minneso:a,?.-. Februa.ry, 29;. 1964.. PublisSed in~Arcbives ofSu;gery, 89: 149, July, 1964.. yk »K 57. Injuries of the Chest Chapter15.ia First Aid,.6th EditSoa; W. H.Oole,F1.D., C..B. Puestov, M.D. 69. (ed5.); Nev York: Appleton-Ceatury Croft, Inc..,.1965,,pp.267-23JL )OK 58'. T.-eataentof Metastasis to Lua:gs;-- Chapter in.Prss in Clinical Cancer,,Voluae I', Irving Arie1,.M.D., (ed)5 ~ r 70. 59. FevYork: Crune & Stratton, Inc..,,19o5,pp• 595:604. Zntrat3oracic Fatty Tumors;~ . ~ with E. ViLson,Stauh, N..D:, and Valter L. Barker, M.D., Diseases of the Chest, 47: 308, March 1965. ' 1. 60i Cardiogvlmona.rvBy'pass.During A'-- --~ S•.irgerl; vith Nillie= E: Neville, M.D., Bob?e Correll,, K.D: a^d Eay~rd P'sbeny M.Dl,. ', PjblisSed in The Jonrr.al of Thoracic and Cardiovascuilar Surpery, 50: r'5> 72. August, 1965.
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0 o1o3y f re vis, e 181 Ven4ils=oryL"prove_e :' Fo1lo-wing Dacart.icamion in Pu? ~orary 41:ber.culosis; ti_',,h talterL. MiD. era nerbe :l:ev:neus, M,D., Presen:.e3 at - Society of Thoracic Surgeons r:eeting,St:: Louis, h'.issouri, Je.nua_ry.25,c 1565. Published inTne P rmsls ofTnoraci'c Sur6e-y,. 1:532, Sep'-e=ner 154-5. ~~K 62. P.i.xone.ry Tuberculosis; - Chapter 7in Sureical Diseases of the Chest, vit.h Willia: ?:.. Tattaey M,D.; 2ad £dition, Brian nln3es, M.D. 'ed ;. St. Louisn C. V. MosbyCo-_a^y, 1966, pp. 176-196. 63... Etiologg by Edict -Editorial; published in The Journa?of;noracicand~Cardiotasculer S.irgery,.51:1+59; March 1966. 64. Postresectional Tnoracic8paces; with HalterL. Barker, M.D. andPaul Neffah,.M.D..; Presented.at the SocietyofTuoracic Surgeons Meeting, Denver, Colorado, January 24., 1956.Publistied in The Annals of Thoracic Surgery, 2;299,.Nay 1966. 65. Empyena Tfboracis- Ed3torial; Published im The Aamls ofT'horacic Surgery, 2:766,.September, 1966. 66. Surgery in Pulmonary,'R,bercul'osis: 11-year Reriev of Indications and Results; aithNelten. L. Barker, M.D:and Marjorie M. Pyle, M.D.; Presezted at the Aserican Surgical Association Meeting,.BocaRatony F:orida, Yar ch 24, 1966, Published'in TheAhnals of Surgery, 164r,567:, October 1966. 67.. 0 Uso de TransfU.saode.Sangue Autologo em Cir,u•gia;vithAlceu L.. Sca.'fa9edreira. M:D.; Published in A.Folba Medica; 53,Nover.ber1966.. Rio de Janeiro, Brazil. - 68. Pl~euralTzbereulosis; with Walter L. Barker,.M.D. end A11anA..Grelan, M.D.;' Presented ct the h7th Ann•aal Meeting.of the American Associat'ion for Thoraclc. S:rgery,, Nev 7ork, NevYork; April 17-19,,1967'. Published inToe Jou.-ne:L of Thoracic andCardiovascular Slugery,5k; pp. 5ll-519;. October 1967. 69. Pseudocavities of the Lung; vithSanSord E. Rabushka, M.D.; Published in The American Revievof Respiratory Disease, 97i:., pp. 644-654,.Apri1 1968. ')'K. 70. sSugery for Pul.nonary.'SSibereulosis; with 'dalterL.Barker, M.D. aadMar,}or1eM.. Pyle„ M.D.; Chapter 11-N in Lev1s' Practice o.'Sur€eryy F. B. El11s,,M:D. (ed.);. Vol. V: pp. 1-7C; Boeber M,edicaL Division, Sa.rper and'Rov,, Inc.; PatilisLers - Bagerste+ny Marylsnd, June 1968.. `'C;+.~ 71.~. 72. The Thorax, Pleura and Lungs;. Chapter 19 1a~Christ'oo3er.'s ;extSookof S•urgeryy Loyal Davis,M:D. (ed); 9t.b,Edition;.n'.: B. Sa,mders Co., Publisaer, Fniladelphia, July 1960.. Also Brazilian Edition. Reduce your 2YYansfusioa Bazard by 50'&'. Get'Of' the "One Traus:l,sion Bock"; vi.t5 George M111es,,M'.D..end 'aill~ir~Da.iessandro, M:D.; Published iL tLe CaicagoMedicine; 71: pp. 655-656;. A•.:6ist hW. . 0 m 0 M.
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182 =i'ri11ojre2cy' of °_sa= T.. Iznbston,, DL2.. Page 7 ' 73. A-.yi._~-s 'can End?. (W3itori=_` ' - ' PutiJlLshed im iae.Annzls ofTnoracic Suur&ery-; 7,:Februa.ry 1969. 74. lrny NottheNnole Truth? 97 i{ C3 Published in Surgery, Gynecolorj . & Obstetrlcs,. 128:pp. 1065-10=5;. ]'sy^,. = ~t 8 1969. 75. Autolo6ous.Transfusion; with GeorSe Milles,.M:D. and Willle.m ~ Dalessent.-o Pablis3ed in A:.D. , , Reviev ofS••u•bery;26: pp. 305-310; Septenber-October 1969. 76. A Sim-l?fied Metbod.for Ma_nageaentof DaLiSs;^.t Pleural Efaision; with Bernard J. LeininSer, Y.D. and Walter L. Be;ker,,M.D..,.Publis3ed Sn . TheJo•arnz3 of Thoracic end.Cardiovascular Surge.y; 58; Pp• 755-763,. November1969. 77,. Tension Pneunoperitoneum end Paeumothcraxint3e TTevbora;; with Bernard J. Leininger„ M:D. and Walrt.erL. Barker, M.D.; Published.in, The Annclt of ThoracicSarSery.;.., 9: pp. 359-363; April, 1970. 3>:K 8 'r~K 8 OK 78. Avtologous.Trans:Sision; with Millee, G; D:lessaadro, WW.; J..Alexar.der Moaog•a;~h Series - C. C. Thomas Publisher, 1971. lst Edition 79:Of Cabbaees--and.Kiaigs- Presidential Address; The JournaliofTLoracioend Cerdiova:scu3es Surgery - 60: 151-156- August 1970. Op?{ OK. 80. Injuries of theCSest, Chapter 15 in Fbergeacy Care - Sur6!oal & t;edicel; , vitSLeininger, B. J. and Barker, W. L.; Edited by Cole W. B..and Puestov,.C. B. 7th Edition.Appleton-CentuxyCrafts, New York, Nev Ycrk, 1y72. 81. Brush Bolder for Endoscopy 82. vithLeininger,,B. J. and Barker, W. L..;Published~in Cbest58:626, De.ceaber,1970. Pacecaker NsL•Sinction vith R_diotelenetry;; 83.. with Leininger,.B. J. and Barker, W. L. end D'Alessindro, U..;.Jou_^mal AMA.215o 796, Fetirvarylc,71 - Letters to Editor. BLood~Transil,.sions; with Y'lles„ G.; D'Alessandro, W.; Journal A.B.A. - Bospitals - Vol. page 63-64,.June,.1970. 8.4. }%P~gement of Persistent Sroncho_cleu_^al Fistulas;; OK 85. with Barker,,W. L.; Faber, L. P:;Osterci Lery W. E..- Journal Tooracic & Cardiovascular Surgery; 62: 3y3-400,Se?tE.::ber 1571. Caree of the Sugieal. Cardiopulncn3-y Pat'3'ent, Chapter 4- The Adult i~o:-e=1e SurgScal Patient;.; vi:,3Barker, W. L.- Ed.i'EorW. E. Iievil?e, lst Sdition,Year Book P'edicel Publishers, Inc. 1971. '
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183 Z I ?iD'_iogre~~;; of Eira:. T: Ir.ngston,,M.D:. ?.oe B !3:• I !xx 86. 4 in c vithLeini.nger., B. J.; Chapter 29 in GeneraliThoraeic Surgery - Editedby. Thomas W:. Shields; Lea& Febiger, Philadelpbia, lyj2:lstEdition 89.Decortication of the Lung; vitb Thos. U. Shields - Chapter 22, in General Thoracic Siurgery- Edited by Thos. il. Shields; Lea & Febiger, Yniladelp*-ia, 1972. lst Edition 87. Diseases of the Pleura; vit4B>.rker,.W: L.; Chapter 28ih General 2Lcracic Surbery- £;ited by Thomas W. Shields.- Lea & FetiiEer, Yailsdeipniay 1572: lst Edi:ion . DY.':85. Pleural Rhors; Knv 90• Surgery.Sor PulmonarylLtierculosis(A3dendum);. with Barker, 9. L. and Pyle, M. k. - LevisPractice ofSutrgeny -£dioed.by F:. Ellis - Thoracic Surgery,.Cbepterlli•7~ Perper Rov., PublisLers, Eas,erst~o'»•ny Y•eryleuid, December 1771. ASitplified~Method of Cnest Wall Reconst:vction;; vitb~Leininger, B. J.; Barker, W. L.- Annals of Thoracio Surgery 13: 358- 360, March 1972. 51. Lung Cancer - Future ProJection; Hireal'. Langston, M.D.; Journal of Tboracie and Cardiovascultr. Surgery, 63: 412-415, Afaroby 1972: 92. Te:ctbook of Sugery- Christopher Davis -10tb Edition, Edited by D. C.S3biston - 1972; W..B. Saunders, Pnile.delpyia - Section.53 - Disorders of . the Lungs,,Pleura and,CbestWall - Chapter 1- The Development oi Thoracic Surgery. . 93.B1ood for Autologous Transfusion B.T. Langston, R.S. [hii^ghan .e.nd, R: MebL - Bulletin De laSociete Internatioorle Db Cnismrgie,,Vol. )XXQ,.No6: 514-519,pov-Dec. 1972. 94„ Clinico PathologicConference No. 145. Painful Chest Wall Mass- Post Gredu- ateHedicine 53:175-178t Featvre Editor H. Sparagaua,y VeteransAdninistration, Hospital,.Hines,.Illinois,.Apri1, 1973. 95. Massive IntrapulmonaryVeno-arteriaD Shunting in Alveolar Cell Carcinoma;. H.C, Fishman; J.Danon; N. Koopot; H.T. Langston: J_T. Sharp - American Review RespiratoryDiseases, Vohnne 109,, page 124-1,28', danuary, 1974. 96. Dmusual Pleural Fiistvlas; with H. Melamed; W. L. Barker;H. T. Langston - The American dournal of Roentgenology, Radium Therapy and Nuclear Hedicine, Volume 120 No. 4, page 876-882. Apri1,1974. 9?', ~ 97. Surgical Diseases of, the Chest - 3rd Editionn witb.W.L. Bask'erand W. H. Tvttle (deceased);. Brian Blades Editor - Chaptez6 - P1eoroputmonary Rl,berculosis. C. V,.MosSy Company„ Pablishers, page 174-201, St. Loois, 2974. a 1 9
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184 -B'.5lcegrenny c=8irmT. rangston, ri.D. P>3e 9 ='~ 98. National Thorncic Surgery.Manpower Study - TheAmerican Association for, N My z Thoracic Sure.rvand Snrintv~f viRli,Brever,.L. A., III, M.D.; Ferguson,.T. B., M,D.; Langstoa, R. T.. i4,D,~ Weiner,J', W., D.P.B.r Cunningham Press. - Los Angeles, ApriL, 1974'. rcofessor of I ., 99. . . SimulatedParaspinai Tumor or Absces's by Ror,.u;dedAtelectasis of the Lover _bcali. Curre )R 00. i.obe; with Hel.amed,.M.; Reynes,.C.;Barker, W. L. - Chest,.Vol. 67, p. 497. April, 1975. Textbook of Surgery - Christopher Davis- 11th'.Editionj Edited by ~` w , ersey Co7 aia scientif _~,lc,y'textboc D. C. Sabiston - W: B. Saunders, Philadelphia - Seetioh 53 - Disordere of the Lungs,. Pleura and Chest Wall - Chapter 1- The Development of Thoranio~g.. .e.al with the Surgery: 1977:_ ~x 101. Surgical Di~seases of,the Chest - 4th Edition an', circulator with W: L. Barker;.Editor ponald B. Effler - Chapter on PleuropuLtionary lbberculosis. C-. V. Mosby Company, Publishers, St. Lo;ai's, Mo. - In Press research, I ha . , 102- Treatment of Chronic Enpyema - Thoraeoplasty sco;;ing and he Movie for American College Surgeons - Narrated at Clini'eal Congress ACS, Chicago. Oct. 1976. ~ c'.e world lite 103, Letter to the Editor ~ was one of 2 . Dual BronchogenicCarcinoma - Ann. Th. Surg.19(3):336, Masch 1975 104. Discussion - Rasults of surgicaltreatment i6.Stage I Lung Cancer. an~ internation 105. Nartin, N.s Beattie, E. 8.- JournalThoracic andCardiovascular,Surgery.74:.499-505,.October,1977. Chest Wa11Reconstruction - B'arker„ W.L.; Leininger, B. J.; Langston, R.T.T, 1977; Dal'Sas October f Sur eons A i C ll i N,cs-noker."1 •.arious aspect 1D6. . . g , can ., e program - mer o ege o Mov American College Chest Physicians, Las Vegas,.Nev.. Novem3er, 1977. Intrapericardial Diaphragmatic Hernia in Adults: Twocases and Review;. ence, not one' . lfeng,. R.L.; Straus,,A.;. Mi11oy,.F.; ]Cittle. C.F.; Langston, B.T; Ia preparation. ex ,,sure of th revvew of the
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Eor Uov 7. ® ers o== ozaciQ nary nasa ACS, 185 STATEMENT OF DOMING&M.AVIADO,. M.D. Nela.Jersey.College of Medicine and Denoistry My name is Domingo M. Aviado. Until recently I was a t:ofessar of Pharmacology at the University of Pennsylvania Medical 1choo,l. Currently, I am~Adjunct Professor of Pharmacology at scv Jersey Colliege of Medicine and Dentistry. I have written .:q}iti scientific monographs, two medical dictionaries, a: pharma- :o.o5y textbook and over 200 published articles, most of which :ea1 witli the effects of drugs and inhalants on~the respiratory ud c rculatory system. In addition to my laboratory and animal research, I have made a continuing study of the liiterature on coking and health. During the last several years, I have reviewed :he k•orld literature concerning smoking and the nonsmoker. ImL979,, :was one of 21 scientists, from seven countries, invited to attend Vl~ir:Lernatlional workshop entitled "Tobacco Smoke Effects on the ~'ons:noker. "l All of the participants had previously investigated :arious aspects of tobacco smoking. During this three-day confer- e:ice, not one conclusive observation was made to the effect that exposure of the nonsmoker to tobacco smoke causes disease. My :eview of the scientific literature published since the conference has revealed no significant change im the state of the scientific k-1owledge on this subjecti. My written statement, which L will leave with you, 0 W ® I 0 IN a 0 ®
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186 contains references to the scientific literature on the subject at hand. My curriculum vitae andilist of publications are also attached. LEVELS OF CARBON MONOXIDE IN SIMULATED CONFERENCE ROOMS Investigations have been carried out,, primarily in Europe, regarding the lievelis of carbon monoxide generatedifrom cigarettes in experimentalifacilities simulating conference rooms containing smokers and nonsmokers. The concentrations of carbon monoxid'e in simulated conference rooms are as follows: Mean No. of ' No. of CO concentration Room cigarettes cigarettes i~ illi h f i d 1 R our parts per m on S ze consume 0 cu m/ e . A 4.5 ppm 80 cu m 50/2 hours 3 2 20 ppm 15 cu m 7/1 hour 5 3 28:ppm 12 cu m 16/1i hour 13 4 30 ppm 170 cu m 105/2 hours 3 5 38:ppm 43 cu m 8A/1i hour 19 6 801ppm 98 cu m 62/2 hours 3 7 The above levels of carbon monoxide were obtained in test rooms that were either not ventilated or poorly, ventiliated. Even though the hourly consumption of cigarettes ranged from13 to 119 per 10 cubic meters of space (size of a closet),, the level of carbon monoxide exceeded 50 ppm in only one out of six investigations. The Threshold Limit Value set by the OccupationaliSafety and Heal!th Administration8 is 50 ppm, which is the maximum level to which workmen can be safely exposedifor 8 hours daily, 5 days a week for their working lives, without experiencing untoward effects. The one experiment in which the carbon m, room was comm the reported situation ex totally unre Th related' to v content were to levels le facilities, 5 ppm even t hour in a sp 7entioned, t eeasurement LEVELS OF CA Ca tration of c cannot discr words, repor smoking sinc kitchens and
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187 Ref. 2 ' 3' 4 5 6 7 the carbon monoxide level exceeded 50 ppm was quite extreme. The room was completely sealed to prevent air exchange and therefore the reported levels of 8-0ippm are of no relevance to the normal tiituatiom expected im publi'c places. I have listed it to show the tota:iy unrealistic nature of many reported experiments. The accumulation of carbon monoxide in the air is directly related to ventilation. As soon as the rooms with a higher CO content were ventilated„ there was a rapid drop in carbon monoxide to :evelis less than 5 ppm~ In public places with normal ventilating facilities, the CO concentration wouldibe expected to be less than 5 pp:n even though as many as five cigarettes are burned in one hour in a space 10 cubic meters in size (equivalent, as I have mentioned, to the size of a closet). This i!s confirmed by actual measurement i~nsidepublic buildings. LEVELS OF CARBON MONOXIDE IN PUBLIC BUILDINGS Carbon monoxide has been used as a tracer for the concen- tration of cigarette smoke in public places, although measurements cannot discriminate between sources of carbon monoxide. In other words, reported levelis of carbon monoxide are not due entirely to smoking since there are many sources of carbon monoxide incliuding kitchens andlautomobile emissions.9 ® 0
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188 T!he 1'evels of' carbon monoxide inside office buildings where cigarette smoking City(C.ountry) Fredericton (Canada) Toronto(Canada). Hamburg (Germany) London (J~ngland). 1.5 to 4!. 5 10 2.4 to 41.6 11 2.7 to 15.6 12 3 to 8 13 The list of public places in which there are measurements of carbon monoxide levels includes: Vancouver: theater - lobby, politicali convention, bingo game, cafeteria less than 10 14 Fred'ericton: restaurants, stores, mallis, banks, bowl'ing alley, legislative assembly less than 10 110 Observations in a reeent Federal Aviation Administration denial of a petition to prohibit smoking in the cockpit, or flight deck, may aliso help to put in context accusations sometimes made with respect to carbon monoxide and smoking. The FAAdeniedi~n. August of 1977 a petition that sought to ban smoking,because of its effect on smoking,pilots and on nonsmoking pilots exposed to smoke. The petition claimed that elevated carboxyhemoglobin levels caused by carbon monoxide produced deleterious effects. Scientists who addressed the problem for the Federal Aviation Administration concluded that no performance decrements were is permitted are as follows: Range of CO Concentra- tibn i~n.ppm References :,3 t A7 found per m; submit crew r LEVEL' to ci, of ni urine nonsm excre amourn the s the N the c resta na.cot whicY invee smoke and ( inha: an a< 34.C
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?tf 189 found in humans during a three-hour exposure of 50 to 2b0 parts per milliion of carbon monoxide. The report.r~ejected material submitted to support a claim of aduerse effects on nonsmoking crewmembers,15 LEVELS OF'NICOTINE IN PUBLIC PLACES The most direct way of measuring the amount of exposure to cigarette smoke by a nonsmoker is to determine the concentration of nicotine in the environment, and the amount excreted in the uriine by the nonsmoker. In the simulated conference rooms,, the nonsmoker absorbed nicotine that was less than 1% of the amount excreted by the cigarette smoker.5 In another comparison, the amount absorbed by the nonsmoker was 5% of the amount absorbed by the smoker.16' Finally,,in a report appearing April 17,, 1975, in the New England Journali of Medicine, Hinds and First17 measured the concentration of nicotine in public places in Boston, such as restaurants and cocktail lounges. The mean concentrations of nicotine were respectively 5.2 and 10.3 micrograms/cubic meter, which i~s far below the Thres}iol&Limit Valiue of 500. These investigators calculated the equivalent number of filter cigarettes smoked per hour for the nonsmoker to be 0.004 in the restaurant and 0.009 in the cocktail lounge. In other word5, a nonsmoker may inhale from 1/100 to 1i/1000 of a filtered cigarette per hour. In an accompanying Editoria1,18 andiresponse to letters,19 Huber 34 -t2I 0 - 78; - 13 C 0 I 11
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190 concluded that these levels of' exposure have no known serious association w1th diseases. He wrote: "The contribution by Hinds and First . . pro- vided a careful and accurate answer to [the question] .... How much tobacco smoke does the nonsmoker passively inhale in public pliaces? Under the most severe concentrations of exposure , the nonsmoker could consume aniamount of tobacco so small'that the risk of' developing an adverse effect would be nonexistent .... REACTIONSoF HEART PATIENTS In the July 6 issue of the New England Journal ofsMedicine,. Aronow20 reported the resulits of a study of 10 heart disease patients' exercise performance before and'after exposure to ciga- rette smoke. This article received widespread publicity because the author concluded that "passive smoking,aggravates angina pectoris." Unfortunately,, the study suffers from nurierous metho3o- l'ogical deficiencies„ including the following: a) Subjective reaction. Aronow states that he carefully explained the potential risks.so as to obtain a written informed consent. It is difficult to ascertainihow this procedure could have f'ailied to affect his findings. In other word5, the subjective symptom of pain was probably influenced by the protocol, and the patients probably expected a shorter duration of exercise time after exposure to cigarette smoke. b) Lack of quantitative measurements. No levels were given for carbon monoxide or nicotine in the experimental rooms. Furtherm absorbed and the occurrin of physi mental t patients very sma should n REACTION smokers between smoke an who disl plain of group ma since th individu has not
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H 191 Furthermore, there are no data to show that nicotine was actually absorbed!by the patients. c) Lack of "blinding" technique. Both the investigptor and the subjects knew when all of the experimental conditions were occurring. This could have introduced bias into the measurement of physiological factors as well as the reporting of symptoms. In short, the Aronow study does not prove that environ- m,ntal tobacco smoke aggravates angina pectoris or that heart patients will develop problems when exposed to,tobacco smoke. A very smalil experiment with serious methodological shortcomings should not be used to reach such conclusions. REACTIONS OF NONSMOKERS Since tobacco smoking first became a part of our lives,, smokers and nonsmokers have co-existed with~ 1!ittl!e, if any, friction between them. There are certain individuals who object to tobacco smoke and these may generally be grouped as follows: (a) those who dislike the odor or are annoyed by it, and (b) those who~cors- plain of irritation, primarily of the eyes and nose. The second! group may be experilencimg!i~rritation~which is not a form of allergy since the reaction may occur in both allergic and nonallergic individuals. Although the existence of allergens in tobacco smoke has not been established, accusations are made that might 1!ead Y I I 0
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192 REFEREN4 one to believe so, Many allergists make use of a skin test involv- > ing tobacco leaf' extract but such skin testing is not at all com, l. R• tJ parable to exposure to tobacco smoke. It is my opinion that should 1' a true tobacco smoke allergy be shown to exist, which has not been 2. Ai (I done, it would be quite rare. Estimates that large numbers of per- 21 sons are allergic to tobacco smoke are unsupported by scientific 3. Li d ta e; 1, . a There are,, I might note, a nearly unlimitedinumber of 4. x: (c substances, including,po3lens, molds, dust, grass andithe like to 01 which some persons may be sensitive. Is it practical, one must 5. He 01 ask, to seek to protect all individuals with such hypersensitivity?' 2: 6. Rii CONCLUSION nc Smoking in public places does not, in my opinion, consti- 7. tc He tute a health hazard to nonsmokers. 8. An 9. Dc Wc Fj 10. mE Ct i7 11. ar Gc 12. tc Ha Ei (Z or Ax
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193 REFERENCES 11. Rylander,, R. (Ed.): Environmental Tobacco Smoke Effects on the Nonsmoker. Report from a Workshop. University of Geneva, 1974,, pp. 1-90L 2. Ander.son,. G.. and Dalhamn, T.: Halsoriskerna vid pasiv rokning (Health risks from passive smoking). Lakartidningen 70:2833= 2836, 1973. 3. Lawther, P. J. and Commins, B. T.: Cigarette smoking and exposure to carbon monoxide. Ann. N!. Y. Acad. Sci. 1i74:1i35- 14'7, 1970. 4. Klosterkotter„ W. and Gono,. E.: Zum Problem des Passivrauchens (On the problem of passive smoking). Z. Bakt. Hyg., I. Abt. Orig. 162:51-69, 1976. 5. Harke,, H. P.: Zum problem des "Passiv-Rauchens" (The problem of: "passive smoking"'):. Munch. Med. Woschenschr. 51':2328- 2334', 197,06 6... Russell, M. A. H., Cole,.P. V. and Brown, E.: Absorpti~onbynon-smokers of carbon monoxide from room air polluted by tobacco smoke. Lancet 576-579„ 1973. 7. Harmsen,, H..and.Effenberger,. E.: Tiobacco smoke in public transportation, dwellings and workrooms. Arch, Hyg. Bakteriol. 141:383-500, 1957. 8. American Conference of Governmental Industrial Hygienists: Documentation of the Threshold Limit Values for Sulistances.in Workroom Air, Cincinnati, 3rd Ed., 1971, pp. 41 43. 9:. First, M. W. and Hinds, W. C.: Ambient tobacco smoke measure- ment. Am. Ind. Hyg. Assoc. J. 37:655-656, 1976. 10. Chappell, S. and Parker, R.: A Study of Carbon Monoxide Levels in Enclosed PublicPlace.s. New Brunswick Council onSmoking. and Health, New Brunswick, 11975, , pp. 16. 8 I a 0 I 111. Godin, G., Wright, G. andiShephard, R. J.: Urban exposure to carbon monoxide. Arch. Environ. Health 25:305-313, 1972. 12. Harke, H. P.: Zum problems des Passivrauchens I.. Uber den Einfiluss des Rauchens auf die CO-Kozentration in Buroraum,en, (The problem of passive smoking. 11. The influence of smoking on the CO concentration in office rooms). Int. Arch. Arbeitsmed. 33:199-206, 1974. 9 2 2
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194 13. Kimura, K.: Some problems concerning the environmental con- di!tlions in office rooms. J. Sci. Labour 49:425-447, 1973. 34. Perry, J.: No smoking. Br. Colum. Med. J. 15:304-305, 1973. 1'S. In,Re Petition of Airline Pilots Committee of 76, Public Citizen's Health Research Group, and Aviation Consumer Action Project, FAA Regulatory Docket No. 15614 (Aug. 22, )i977). 16. Horning, F.. C.,, Horning, M. G., CarrolLl, D. I., Stillwe7l, . R. N., and Dzidic, J.: Nicotine in smokers, nonsmokers, and~ room air. Life Sci. 13:1331-1346, 1973. 17.. Hinds,. W. C., and First,M. W.: Concentrations of nicotine and tobacco smoke in publ~ic places. N. Fngl. J'. Med. 292:814- 815, 1975. 18. Huber, G. L.: Editorial. Smoking and nonsmokers - what iss the issue?' N. Engl. J'. Med. 292:858-859, 1975. 19.. Huber,. G.L.:Letter to the Editor. N. Engl. J. Med. 293:0-49, 1975. 20i. Aronow, W. S.: Effect of passive smoking om angina pectoris. N. Engl. J. Med. 299:21-24, 1978. s Bo Ch
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t r Bbrn: 195 CURRICULUM.VIi'TAEDomingo M. Aviado,M.D_ August 28,. 1924 - Manila,Philinpines; Citizen of the Philippines possessing a permanent visa to the U.S. since 1952. Married Asuncion P. Guevara, August 15, 1953. Children- Maria Cristina (born June 28, 11954), B.S.-M.S. University of Pennsylvania, 1976_ Carlos Guevara (born March 2, 1957), University of Rochester, Class of 1979. Domingo Guevara (born August 1', 1959), Groton School, Class of 1977. Maria Asuncion (born June 11, 1962),. Groton School, Class of 1981. College Education: University of the Philiippines College 1940-1942' of' Liberal Arts University of the Philippines Coll'ege 1942-1945 of Medicine University of Pennsylvania School 1946-1948 of Medicine Doctor of Medicine, University of Marchil948: Pennsylvania Present Position: Senior Director, Biomedical Research, Corporate Medicall Affairs, Allied Chemical, Corporation Adjiunct Professor of Pharmacology,, N. J. Medical School Academic Positions at the University of Assistant Instructor in Pharmacoliogy Instructor in Pharmacology Associate in Pharmaco,logy Assistant Professor of Pharmacology Associate Professor of Pharmacol'ogy Professor of Pharmacology Member, Parasitology Graduate Group Acting,Chairman of Pharmacology 1977-present 1978-present Pennsylvania: 1948-1i949 19 49-1i9 50 1950-1~953 1953-1960 1960-1965 1965-present 1967-1977 1969-1970' IN a
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0 196 Miscellaneous Positions: National Institute of Health Post- 1948-1950: Doctorate Research Fellow Assistant Attending Physician of 1955-1972 Cardiology, Philadelphia General Hospital Visiting Lecturer in Anesthesiology, 1955-present Albert Einstein Medical Center Visiting Professor of Pharmacology, Univ- 1959-present ersity of the East Medical Center Editors (Philippines) Visiting Lecturer in Physiology, Women's Medical College 1961-1962' Consultant, Poison Control Program of 1964-1970 Philadelphia visiting Lecturer in Physiology, Rutgers University 1966-1967 Member, Ad Hoo Committee on Air Pollution and Air Hygiene, Philadelphia, Medical 1967-1969 Society Member,, Bronchopulmonary Panel of National 1'969-1970 Clearinghouse for Smoking and Health Chairman, Medical Adui'.sory, Committee, to the Cliini'cal Research Center, 1969-1970 Honors: Graduate Hospital of University of Pennsylvania Member, American Heart Association Ad Hoc 1969-1970: Committee on Cigarette Smoking Consultant, Council for Tobacco Research 1972-1973 United States Pharmacopeia; Delegate to 1976-19:80 1975 Convention; Member, Advisor Panel on Allergy, Immunology and Connective Tissue Disease National Institute of Occupational Health, Review Consulitant for Criteria Document 1976- National Academy of Science-National 1976-1979 Research CounciL Commi~tteeon,.U. S. Army Basic Scientific Research University of Rochester Member of the 1976-1979 Parents' Council National Institute of Drug,Abuse, Review 19'77 on Inha1'~ant Abuse Participant National Center for Toxicological 1947 Research, Member of Inhalation Toxicology Committee Department of Health, Education and WeLfare7 Consultant to the General - 1977 Counsel on Enforcement, Food and Drug Division Nationali Institutes of Health, Member of the Neuropharmacollogy Study Section 1978 American College of Clinical Pharmacology, Member of the Board of Regents American College of Toxicology, Chairman, 1978-11983 Inhaliation Committee 1978' Scientific Advisory Board, Envi~.ronmental. Protection Agency, C7ean Air Comimittee1978
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197 Ed~.i~torship.: Honors: Aviado - .. Section Editor of Chemical Abstracts 1952-1950~ Associate Editor of Circulation Research 1955-1962 Editorial Consultant of Dorlands' Illus- 1963-1967 tratediMedical DictionaryEditorilal Consultant of Stedman's 1972-1975 Medical Dictionary,. 23nd Edition Member„ Advisory Editorial Board of' 1965-present Archives Internationaliesde- Pharmaadynamie et de TheraPie Member, Editorial Board of Cardiology L967 present Editor, Scalpel and Tongs, Journal of 1971-1974 Medical PhiLately' Menber, Editorial Board of Drug 1974-present Informatibn Journal' Editor,Journa.l of' the Association 1976-present of Phili~ Practicing Physicianss in America.. . Alpha Omega Alpha Honorary Medical Society. Member 1'946 Travel Award, Rockefeller Foundation 11961 Linnaeus Medal, First International 1961 Pharmacological Meeting, Stockholm, Fellow of the Guggenheim Foundetion 1962-1963: Purkiinje Medical, Second International 1963 Pharmacological Meeting, Prague Physician of the Year Award, Philippine Medical Association (Chicago) 1969: University of Pennsylvania Under- gradtUate Teaching Award. 1971 University of Santo Tomas Luis 1972 Guerrero Hono.rary Lecturer - - Lindback.Award for Distinguished . 1974, Teaching,, Unilversity of Penna. Presi~dential Trophy (Philippines)' for 1975 Most DistinguishediFilipino Abroad Apoli~nario Mabini Educational' Award,, 1975 Association~of Phili'ppinePractici~ng. Physicians in America Honorary Member, Farmacologia y mental Sociedad Peruano de Terapeutica Experi- 1976 Honorary Member,. Angiologia Societ'aItalianodi~ 1977 Embassy of the Philiippines to the Uhited States Delegate to the 1977 American~Academy of Political and Social Science 9 1 0 m Eim H
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198 :,vlado Societies: Physiological Society of Philadelphia: Member, 1948; Secretary,, 1954-195B; President, 11959-1960; Councillor, 1960-1961. American society for Pharmacology and Experimental Therapeutics: Member, 1950; Co-Chairman, 11965 Fall ?^.eeting: Member Finance Comar,ittee, 1965-1970; Member Committee on Environmental Pharmacology, 1975-1976'. American Physiological Society: Mem:ber,, 1951. American Associatiomfor the Advancement of Science„ 1951. The Soci~ety of Sigma XI: Member, 11952. John Morgdn Society of the Universi~ty of Pennsylvania: Member, 1956; Life member, 1967. American Heart Association: Member, 19:57; Member Research Study Committee, 1965-1967. Section on~Pharnacology (SEPHAR): International Union of Physiological Sciences-Treasurer, 1959- 1965. I'nternational Union~of Pharmacology (IUPHAR): Treasurer, 1i965-1966. American Society of Tropical Medicine and Hygiene: Member,,1966. International.Leprosy Association: Member, 1967'. American College of Clinical Pharmacology; Charter Member,, 1971; Chairman, Long Range PLanni~ng Committee, 1976. - Society of Toxi'coliogy: Mem.ber, 1971. Drug Information Association: Merrber,. 1973. American~Medical Association: Member,. 1974;,.. College of Physicians offi Philadelphia: Fellow, 1975. Biograohi;cal Data 1isted, i;ne American Meniof. Science - 1955 .Leaders in American Science 1961 Wor1d Who's Who imScience (Marquis) 1968 Dictionary of International Biography 1970 Who's Who in America (Marquis)l 1'976 Who's Who in the East (Marquis) 1977
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199 LIST. OFPCSBLICATIONS Domingo '-`4.. Aviado,`ii.D. Page I. Monogranhs;.Textbook and Dictionaries 1. LT. Respiratoryy and Cardiovascular Reflexes (1949-1962) III. Pathologic Physioloc,ry and Pharmacology of the Pulmonary CircuLation (l952-196'4) IV. Sympathornimetic Drugs (1957-1963) Hynoxiia and'Autonomic Blocking IDrugs (19fi0-1971) VI.. Bronc:hodi'lators,. Antiast_hmati:cs and Antitussives (1.964-197.5)~ VILD. PulrnonaryEmphysem,.a, Prog.estational. 10Stieroids and Tobacco (1965-1976) VS=i. Circulatory Shock, Pulmonary Insufficiency 14 and Perinheral Vasodilators (1965-11976) Coronary Vasodilators and'Cardioactive 16 Agents (1966-1975) ?'r.a-rn:acolloay and Toxicity of New Anti- 18 malarial Drugs (1967-1972) Inhalat~onal Toxic.itv of Aerosoll 22. Propellants and Solvents (1971- )i XTII. Clinical Pharmacology (1975- ) 24 F.eview articles are indicated by amasterisk (*). A1L others in the numerical list are reports of original imvestigation.. 0 ® 0 0 8 H
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200 LIST OF.PUBLICATIO.}S Domingp M. Aviado,, M.D. I.MONOGRAPHS-,. TEXTBOOK AND DICTIONARIES Druas and Resoiration. (Proceedinqs.of the Second'Interna.tional. Pharmacological Meeting) Edited by D. 1,11. Aviado and. F. Palecek, Vol. 11. Pergamon Press, pp.1-241, 1964. Pharmac_olo_qy_of the Lu~ (Proceedings of the First International Pharmacological Meeting): Edited.by, D.M..Aviado, Vol.. 9',, part 2. Pergamon Press Oxford, pp.97-193, 1963. The Lung Circulation. Vol. 1. Physilologyand Pharmacoloay;, Voli. 2. Pathological Physiology and Theraoy of! Diseases,,D. ML Aviado,. Pergamon Press,Oxford,, Vol. 1. pp.1-590; Vol. 2. pp.591-11405, 1965. Dorland's Illustrated Medi'.cal. Dictionary. Pharmacology and Toxicology'words Edited.by, D. M... Aviado,. 24th.Edi.tion, W. B. Saunders Company, Philadeliphia, 11965. Antitussi~ve Agents. (Section 277 of Internationali Encyclopedia of Pharmacology and Therapeutics). Edited by H. Salem and,D. M. Aviado, PergamonPress., Oxford,.VoL. 11, 2 and 3, pp.1-834, 11969. S1-.cat`iomimetic Drugs. D. M. Aviado, Charles C. Thomas, Springfield, pp.1-615, 11970. Ph_=a¢ologic Princiules of Medical Practice. D. M. Aviado,8th Edition, The Williams and Wilkins Co., Baltimore,, pp.1-1345, 1972. Sted:.an's Medicall Dictionary. Pharmacol!ogy and Toxicology words Edited by Ds M. Aviado, 23rd Edition, The WilQiamsand Wilikins Company,Baltimore,, 1976. hyl Chloroform and Trichlorethylene in the Environment. ;4etl D. M. Avilado, J. A. Simaan, S. Zakhari and A. G. Ulsamer, CRC Press, Cleveland', Ohio, pp.1115, 1976. Nonfluorinated!Propelliants and!Solvents for Aerosols. D.. M..Av.iadoj S. Zakhari and T.Watanabe,CRC. Press,. Clieveland, Ohio, 1106 pages, 1977. II. RESP: 11. The r. and p R'. G. 97: 4 2. The m vario chemi Ji. Ph 3. Respil and'p Li, W M. R. 1951. 4. Early' antog, Schmi 5. The a crani A. Ce Exp. 6. Refle and'] 35: : 7. Cardi o f ti Phys: B. Para: Edilt( 6c 2' 9. Some D. M *'l0. Resp Avia Luis Isopropanol and Ke.tonesi!n_th_e Envtronment. S. Zakhari, M. Liebowitz, P. Levyy andD.M.Av.iado, CRC Press, Cleveland, Ohio, 155 pages, 1977.
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201 DMA - 2 II. RESPIRATORY AND CARDIOVASCULAR REFLEXES(194'9-19b2) 1. The reflex respiratory and circulatory actions of' veratridine and pulmonary,, cardiac and carotid receptors. D. M.Av.iado., R. G. Pontius and C.. F. Schmidt. J. Pharmacol. Exo. Ther.. 97: 420-431, 1949. 2'. The mechanism of apnea fiollowing intravenous injection of various antihistaminic compounds; its relation to their chemical structure. D. M..Aviado,. R.. G..Pontius and T. H. Li. J. Pharmacol. Exp. Ther. 99: 425-431, 11950. 3.. Respi.ratoryand circulatory reflexes from the perfused heart andipulmonary circulation of the dog. D. M. Aviado, T. H. Li, W. Kalow, C. F. Schmidt, G. L, Turnbulll, G. W..Peskin, M. R. Hess and A. J. Weiss. Am. J. Physiol._ 165: 261-277, 11951. 4. Early respiratory depression by curare and curare-potassiurn anto.goni,sm. T. H. Li,. B. R,. Jacobs, D. M... Aviado and C.. F. Schmidt. J. Pharmacol. Exp. Ther. 104: 149-1i61, 1952'. 5. The activation of carotid sinus pressoreceptors and intra- cranial receptors byveratridineand:potassium. D. ML Aviado,. A. Cerletti, T. H. Li andiC. F. Schmidt. J. Pharmacol.. Exp. Ther. 1115: 329-338, 1955. 6. Reflexes from stretch receptors in blood vessels, heart and lungs.. D. M. Aviado~and'.C.. F. Schmidt. Phy.siol. Rev. 35: 2A7-3001, 1955. T. Cardiovascular and respiratory reflexes fromithel.eft sideofe the.heart. D. M. Aviado.a.nd C. F. Schmidt. Am. J.. Physiol. 196: 726-730, 1959. 8. Paralleli lines, infinity and cardiovascular reflexes. Editorial. C. F. Schmidt and D. Mi. Aviado. Circ. Res. 6: 229-231, 1958'. 9. Some controversiali cardiovascular reflexes. Editorial. D. M. Aviado. Circ. Res. 10: 831-835, 1962. *10. Respiratory influence on cardiovascular function. D. M. Aviado. Inc Cardiovascular Functions. Edited by A. A. Luisada, Vol. 2, MeGraw-Hill, New York, 226-229,, 1962'. 0 I t Q
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D1LA IIIi. PATHOLOGIC PHYSIOLOGY AND PHAR`^:.•1COLOGY OF THE PULLMONARYCIRCULATION.(1952-19b4) 11. Effects of anoxila on Pressure, resistance and bloodi(P32) volume of pulmonary vessel's. D. M. Aviado, A Cerlietti, J. Alanis, P. H...Bulle and.C..F. Schmidt. Am. J._P_hys_iol. 169: 460-470, 11952. 112. Respiratory burns wilth spe.cial reference to nulimonary edema and conge.stion~. D. M. Aviado andC.. F. Schmidt. Circula- tion. 6: 666-680, 1952. 13. Eff'.ectso.fi pulmonary embolismm on the pultrnonary circulationwithispecial reference to arteriovennus shunts in the lung. A. H'. Niden and Ds M. Aviado, Circ. Res. 4: 67-73, 1956. 14. Effects of sympathonimetic drugs on pulmonary circulation with.special reference to a newp.ulm:onary, vasodilator. D. Mi. Aviado and C. F. Schmidt. J_. Pharmacol. Exp:. Ther._ 120: 512-527, 1957. 15. Pathogenesis of pulmonary edema by alloxan. ID. M. Aviado and C. F. Schmidt. Circ. Res. 1'80-186, 1957. 16. Effects of anoxia on pulmonary circulation: reflex pul- monary vasoconstriction. D. M. Aviado, J. S. Ling and C. F. Schmidt. Am. Ji. Physiol. 189: 253-262, 1957. - 17. The effects,of aminophylline and other xanthines on the pulmonary circulation, C. W,. Quinby, Jr., D. M. Aviadoo and C. F. Schmidt. J. Pharm.acol.. Exp. Ther.. 122: 396- 405, 1958. 18. Therapy of experimental pulmonary edema in the doq; with special reference to burns of the respiratory tract. D. M. Aviado. Circ. Res. 7: 1018-1030„ 1959. 19. Physiologi~c bases for the t'reatment of pulmonary edema. D. M. Aviado and C. F. Schmidt. J. Chronic Dis. 9: 495-509, 1959. 20. Respiratory influences on cardiovascular function. D. M. Aviadb. Cardiology. 2: 226-229, 19'S9. 21. Pharmacology of the pulimonary circulation. D. bi. Aviado. Pharmacol.. Rev. 12:. 159-239, 1960. 22. Effects of acute atclectasis on liobar blood flow. Ds M. Aviado. AmI. J. Physiol. 1198: 349-353, 1960. 23. Pulmon and hi 1036, 24. Digita D. M. 25. Refler of pul: Arm. Ji. 26. Nervoi Aviadc 4'4 6'- 4 `_ 27. Contri admixi M. del 1!55: f 28. I'nhal< bronck Salem 662„ . 29. Local of dri Mata , 295-3i 30. Effec pulmo: D. M. *31. Pharm refer pulmo 1961. *32. Struc lungs 1:962. 33. Respo prepaand D 34. Facto 5-hyd Res.
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203 DIN:A - 4 23. Pulmonary venular responses to anoxia, 5-hydroxytryptamine and~histamine. D. M. Aviadb. Am, J. Phvsiol. 198: 1032- 1i036, 1960. 24. Digitalis and the pulmonary circulation. Y. S. Kim and D. M, Aviado. Am. Heart Ji. 62: 680,686, 1961 25, Reflex stimulation of heart induced by partial occliusion off pulm,onaryy artery. A. C. T.aq!s.imi and D~. M. Aviado. Am. J. Physiol. 200: 647-650, 1961. 26. Nervous influences on the pulmonary circul'ation. D. Mi. Aviadb. Naunyj SChmiedeberg's Arch. Pharmaco L. 240: 446-452, 11961. 27. Contribution of the bronchial circulation to the venous admixture in pulmonary venous blood. D. M. Aviado, M. deB. Daly, C. Y. Lee and;C. F. Schmidt. J. Physiol. 1155: 602-622, 11961. 28. Inhalation of sulfur dioxide. Comparative behavior of bronchiolar and pulmonary, vascular smooth muscles. H. Sal.emand D~ M. Aviado_ Arch, Environ. Health. 2: 656- 662, 1961. 29. Local and reflex effects of bronchial arterial injection of drugs. J. Martinez, L. de Letona, R. Castro de la Mata and D..M. Aviado. J. Pharmacol. Ex._p..Ther. 133; 295-303,, 1961. 30. Effects of nerve stimulation and drugs on the extra- pulmonary portion of the pulrnonary, vein. M. Eliiakim and D. M. Aviiado. J. Pharmacol. Exp. Ther. 133: 304-312,, 1961. *31. Pharmacology of the pulmonary circulation: with special reference to drug therapy of pul'monary hypertension and pulmonary edema. D:. M, Aviado. Lancet. 61: 311-315, 1961. ~ *32. Structure-activity relationships of drug affecting the lungs. D. M. Aviado. J. Pharr,.aco1. Sci~. 51: 191-201, 1962. 33. Resoonses of the bronchial veins in a heart-lunc bronchial preparation. P'. Aramendia,.J. Martinez, L. de.Letona and D. M'. Aviadb. Circ. Res. 10: : 3-10, 1962. 34. Factors.influencing pulmonary hypertensive resDonseto 5-hydroxytrytamilne. J. Duteil and D. M. Aviado. Circ. Res. 11: 466-473', 1962.  0 ® 1 0 9 ®
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Dla;?' Page 5 35. Exchange of blood between the pu.imonary, and systemiecirculations via bronchopulmnnaryanastomoses: pulinonary arterial~ligaSion, embolization and inhalation of heat.P.Ararnendia, J. Martiuez,. L. de Letona and.D.M. Aviado.. Circ.R'es.11i8/0-8191 1902. 3b.*Pharmacologyofthe bronchial.circulationwi2h.special refereneeto a newhomeostaticw meenanism forbroncnornotor tone. Inr. _Phar-^.ecolo,v of the Lung (Proceedings of the First'Ihternational.Pharmacolooicali Meeting).. D.M. Aviado, Voll 9. Pergamon Press, Oxford'i pp. 12:5- 149,. 1i9.63• 37.; Phar~macolooyofthe Luna. (Proceedingsoflthe Fiist..InternationaP. Pha:rmacological Meeting)i Edited.byD. M. Aviado,. Part 2, Vo1.9• PengamonPress, Oxford, pp. 9.7-189.. 1903. 38.:* Chemical therapy of pulmonaryy edema. D. M. Aviado. Biocnemical Clinics: The Lun2 . 4; 273-279,, 119b4. IV. SYMPATHOMIMETiIC DRUGS (1957-1963) 39: Mechanisms for cardiac slowing by methoxamine. D-M: Aviado and A.L. Wnuck. J. Pharmacol. Exp. Ther. 119: 99-106, 1957. 40. The effects of molar sodium lactate on cardiac function: an experimentsl' study in dogs. S. Bellet, S. V. Guzman, J~ W. West.and D. M. Avi.ado. Am. J. Med. Sci. 233: 28b-295, 1957. 41.*DYugsaffecting thecard'novascular system.. ID.M. Aviado and C. F. Schmidt. Inc Handbook_o` Biological Data. Edited by W,-S. Spector. Table 333 in four parts, pp. 37o-382, W. B'. Saunders, Pnilad'elphda„ 195 1. 42Lt`Hypotens.ion and the autonomic nervous system. D.M. Aviado. , Ann. N. Y. Acad. Sci. oo: 998-1009, 1957. 43'. Cardiovascular effects of syrnpathomimetic.broncnodilators: epinepnrine,, ephodrine, pseudoephedrine, isoproterenol, methoxyphenamine and isoprophenamine. D. M. Av.iado„ A. L. Wnuckk andi E. J.. DeBeer. J_Pharmacol. Eicp. Ther. 122: 406-417, 1958. 44. The effect's of sympathomimeticdru;s onrsna1 vessels. D. M. Aviado, A.L. Wnuck and E:J'. DeBeer. J_Pha_rmacol._E?cp. Ther. 124: 238- 244', 1958. 45. Acomparati. D. M'. Aviad b'9: 598-60 46. *: Cardiovasci. Aviad'o. An 47+*New.sympat Editorial. 48. ° Cardiovasc, Compiled b Researcn C PP• 245-2' :}9.. *: Connecting Editorial. V. HYPOXiA 5D. Effects of ; J. Litwin, 51. Effects of control. I: 129:' 330-: 52'. # HemodynaCirc. Res 53. # Syrnpathet~ TdWi-10, B Am. JL M 54. Differentil resistanc< D.lvlL Avi 55.. Role of cc output dlrl Jt Physic 50. Stimulat;i Penna an, 1902'. 34-121.0 - 78
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205 Dh1A~ Paz -2 6 45. Aeomparative study of nasal decongestion by sympathomimetic drugs. D. M. Av.ia9o„ A. L. Wnuck and E. J. DeBeer. Arch.. Oto1'ary~,,,i._ b9: 598-60 5, 1'859: ta1'. q 3.4-121 0 - 78'- 14 45~..= Cardiovascular effectss of sorneo c.ommonly used pressor amines. D. M. Aviado. Anesthesiolbeg- 20s 71-97, 1959. 47. * Newsympathomimeticdrugs with selective cardiovascular actians.. Editorial. D.M. Aviado. Circ. Res. 7: 815-81i7, 1959- 43. `~ Cardiovas.cnlarr drugs. D: M. Aviado. In: Handbo_ok_of Circu?ation, Compiled byP.11. Altman for the NationalAcademyof'.SciencesNational Researcn CouncilL Tables 108'- 112,, W. B.. Sau..ldersCo. , Philadelphia, pp. 246-27Z, 11959. Connecting links to solve discrepancies of actions of prossor drugs. Editorial. D.M..Aviad'o. Anesthesiology. 24:. 7o3'-tcu4, 1903. V. HYPOXIA and AUTONOMIC BLOCKI.NG DR'UGS (19h0-1971) 50. Effects of anoxia on the vascular resistance of tne dog's hind limb. J. Litwin, A'.H. Dil and D. M. Aviado. Circ. Res. 8: 585-593, 1960. 511. Eff'ects of a new sympathetic blocking d'rug (Bretylium) on cardiovascular control. D.:vl. Aviado and A. Ht Dil.- J.. Phar,macolt Exn. Tner. 129: 330-33i, 19o0t ! 52. = Hemodynamic effects, of' ganglion blocking drugs. D: M. Av.iado- Circ•Res. 8: 304-314!, 1900.. 53, * Sympathetic nerve blocking drugs for the treatmentt of hypertension6 TM- 10, Beta. Tm-10', Bretylium and guanethidine. D.h:'. Aviado.Am. J. Med. Sci. 244: 650-661 , 1961. 54. Differential', r~esponse of renal andd fe:norali b;ood flowss and va=cular resistances hypotensive and~ hypertensive procedures. J.C- McGiff and! D.M. Aviadb. Circ. R~es. 9: 1327'-1335, 19*j1. 55. Role of carotid'andlaortie bodies in mediating the increase in cardiac output durino anoxemia. M.. Penna, L.. Soma a.nd! D. M. Aviado. Am. J_Ph,ysioa. 203: 133- 136„ 19b2. 50. Stimulation of aortic body, cnemoreceptorsbyganglionstimulancs. M.. Penna aaidD. Ms Aviado. Arch. nt. Pha-rnacodyn.. 140: 2b9-230.,. 19b2. ----I---------- 0 0 0
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206' DMA Pa;e 7 68.: 57. Pharmacological studies of hexamet}:yle.ne-bis-carbaminoylcho'ine. (Imbretit) on the cardiov.ascular and respiratbry, systems in dogs. S. Saito and'D.Ms Aviado. Jpn_Circ. J. 27: 791-79b, 19b2. 5i1•. Influence.ofbretyliumon.responses of thehe.art-lung preparation:, DMPP'and'.partial occlusiowofttiepulmonaryartery.. R. Castro 69.; de la;Mata, P. Aramendia, J.. Martinezde Letonaa and D.M. Aviado.J. Pharmacol. Exp. Ther. 135: 15o-1o3', 19o2. 59. Reversal of sympathomimetic bronc.hodilartation.by dicliloroisoprotercnol. R. Castro de.la Ivfata,Ml Pennaland D.M', Aviado. J. Pharrnacol. r Exp: Ther. 135: 197-203, 1962. V1. 60. Effects ofhypercapnia on thevaseular resistance of tnedog's nind'i1imb. J. Litwin, A. H. Di1 and D: M. Aviad'o. Pflu¢er Arcii, 277: 3'87-39b, 19b3. 70:*' bl'.-` Neww perspectives on the therapy of respiratory failhreand lung injury. In: Drues and'.Respiration. (Proceedingsofttie Second Inter:national. Pharmacological Meeting)~ D:M. Aviad'o, Vol. 11. Pergamon.Press, Oxford, pp. 229-z32', 19b4. 71. 62'$ Car~diovas.cular pharmacology. D,M. Aviado. Ann... Rev. Pharmacol. 4: 139-154, 1964'. 72. 63. Mechanism for bradycardia arising from stimulation of carotid bodies. H. Salem, M. Pennaa and D.IvI.. Aviado. Arch., Inb. phaimacodl.n. 1150: 249-258, 1964. 73. 64. Mechanism for cardiac stimulation during anoxemia in the modified heart'-lung prepatation. L. R. Soma, M. Penna and D1.M:.Aviado. PfluRer Arch. 282: 209-224, 1965. 74. 65~* Pharmacologic approach to the treatment' of shock. D. M. A:viadb. Ann. Intern. Medi 62: 1050-1059, 1965. 66.. Cardiovascular effects of: anoxia and the in.fluenc:e of a new bet~~ adrener- 75. gic receptor blocking drug. Ib. E. Folle and~D. Nl. AviadoJ. Pharmacol. Exp. Ther. 1t}9c 79-90, 1965. 67. * Ganglion stimulant andiblbcking drugs..D.M. Aviado. In: Drill's Pharmacolog y in Medicine. Edited by J. DiPalma 3rdEdition 76. . , .McGraw-Hi111 New York, pp. 524-543, 1965.
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207. DMA Page 8 68. * Pnarmacology of hypertension witth special reference to the cardio- vascular effects of beta-adrenergieblocking ag,ents.: D. M. Aviado. In:. Advance=in.Cardionuln-ronarvDiseases. Ecited'byA.L. Banyai and B.:L.. Gondon~ Voll IV. Yearbook Medical Fablishers,. Chicago, pp. 129-143, 1969. 69. * Ganglionic stimulAnt and blocking drugs. D. M. Aviado. In: Dril'1's PharmacologyinMedicine.Edited by J. DYPalrna, 4th Edition.~ McGraw-Hill, New York, pp. 708-734, 1971. VI. BBONCHODILATORS, ANTIASTHMATICS AND ANTITUSSLVES (1964-1975) 70.* Antitussive drugs with special reference to a new theory for the initia- tion of the coughreflex.and~theinfluence of bronchodilators.H. Salem an6 D. Ml Aviado. Am. J. Med. Sci. 247: 585-600, 1964. 71. Bronc?,odilatation by, a vater-solublee derivative of theobrornineadmi~nis- t~ration.by var~iouss routes. D. M. Aviado and V.:A.. Patel. Arc`.r.Lnt. PRarmacodyn: 150: 336-347, 1964. 72. *Pharmacological approach t~oo tr.e.atrnent of atopic dis.ordere. D.M.. Aviado. In: Immunoloeical Discases. Edit'ed by M. Samter„ Little Brown and Go., Boston, pp. 612-626„ 1965. 73,. Interrelationships betwe.enpuLmonar.y blood flow and bronchornotorr tone: POZ and PCpZ. M. Samanek and D. M. Aviado. J. Apnl. PhysioL 22: 719-730, 1967. 74. Mechanilsmfor the reductionin~pultnonary re=istanceinduced1by halothane.A.:M. Klideand! .D.M~ Aviado.: J.. Fharmacol'. Exp. Ther. 158': 28-35, 1967. 75. Pharmacologic potency and selectivity of a new bronchodilEitor agent: soterenol' (A'[J 1992). K. W. Dungan, Y. W. Cho, A. W. Gomoll, D: M. Aviado and P: M. Li'sh., J. Pharmacol. Exp. T`ter. 164: 290-301, 1968. 76.. . FSfirccy d'a new.bronchodilator, soterenol', onexperimental locked-lung syndrome in dogs. Y. W. Cho, D: M. Aviadb and! P. M. Lish.. J..°.]le.re. 42: 36-48, 1968. I 0 F ® ®
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208' 77. Bionchodilatoryaction ofpentaerythirtyl te.traniitrate in ea-peri- Xant~ mentalipulmonary emboli~sm~ D. M. Aviado, M.. Samanek,. i~~. and S. Belleti. Cardioloeia. 52: 340-361, 1968. Palecek H. S 78. Me.chanisms for the bronchodilatoryeffeets of cor4icosteroidss in the 91. • Antia Unitc sensitized rabbit. L. R. Carrillo and' ID. M. Aviedoa J'. Pharmacol. 822 Exp. Ther. 164: 302-311, 1968. , 79. Bronchopulmonaryandlcardiac effects of hydro:cortisone. M. Cskoui i2~..* Topi~ and D. M. Aviado. Arch. LnY. Pharmacodyn. 179: 314'-325, 1969. H. S 80. Cardiopulmonary effects of.norepinephrinef and propranoloL. M. 9.3.~* Phar d M O>koui and D. M. Aviado. Eur: J. Pharmacol. 5: 321-327, 1969. . e 81. Monocrotaltne-induced. pulmonary hype.r,tension and p-chlorophenyle- 94. * Prec d lanine (PCPA). L. R.. Carrillo and. D::vf.Aviado. Lab... Inve=t. 20:. a an 243.248, 1969. mati 82. The nasal'and bronchopulmonary effects of oxymetazoliae and KB 227. 95. * Prec S H L. Carrillo, T. kishirnot'o and D! M. Aviadb. A-nn., Oto1L 78: 1-10; . 831 . Bronchopulmonary and gastrointestinal effects of lobeline. P. J. 96. Antit i Cambar, S. R. Shore and D. M. Aviado. Arch, Iht.. Pharmac an B 177. 1-27, 1!969: 1975 84. Bronchopul:nonary effects of a reduction in oxygen content of bibod 97. Antit d c perfusing the pulmonary artery. V. Marco, C.D. Park, and D.M. tio 313 i 9 R i 26 3' A 6 1196 an Phar 85. - v a o. eso ra n. _ : ,. 9. Antiasthmatic action of corticosteroid's: a review of the lit'erature on their mechanism of action.. D; M. Aviado and L. R.. Cairriilb. J. Clin. Pharmacol. 10: 3-11i, 1970. ! Vll. PU: 86. Antiasthmatic action of sympathomimetics: a review of the literature ontheirbronchopulmona.ryeffects. D.M. Aviadb. J_Clin, Pha.rmzcol. Bror B 10: 217-221, 11970. 9 . 87. Bronchopulmonary effects of paraquat and expectorants. P.J, Cambar cons M, / 65 1 and D. M. A•riadb. Arch. Environ. Health. 20t 488-494, 1970. 9 88. Bronchopulmonary effects of caffeine in the anesthetized~dog. M. 99. Bror Oskoui,. D. M. Aviadec and S. Bellet. Respiration. 27.:63-73; 1970. Bror 89.* Sympathomimetic bronchodilator preparations available in the United and : States. D. M. Aviado and lI. Salem. Rev. A11er= 25: 441-4'50„ 1070. 1001 Bror reflt and -
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209 ?d e n ss DMA. Page 10 90.+ Xanthine bronchodilator preparationsavailabie in the United Stat'es... H..Salemand.D.M. Aviado, . Re.v: Allerg.., 24: 624-630,.11970i 914 * Antiasthmatic preparations containing corticosteroids available in the United States. H. Salem and D. M. Aviadb. Rev. Allere. 24: 8'1i9- BZ2„ 1970. . 99Z. * Topical nasal deoongestant preparations available in the United States. H. Salem and D. M. Aviado. Rev. Allerg. 25: 271-277, 1971. 93, * Pharmacology of: antiasthmatic drugs. D. M. Aviadb. Atti Acad. Sai. Med. Chir. 127: 158-173, 1973. 94. * Preclinical and clinical investigation of drugs. I. Bronchodilators and antiasthmatic:drugs. H. Salem and DI M. Aviado. DrueInfor-mat'ion Bulletin. B; 14-19, 1974. 95. * Preclinibal: and: clinical investigation of drugs. II. Antitussive drugs. H. Salem and D: M. Aviado. Drug Inf. J. 8: 111-143, 1974. 96. Antltussive Drugs. 1. Car~diopulmonary effects.ofcod'eine. A. Bianchi and D. M. Aviado. Arch. Int. Pharmacodyn. 216c 208-2'1i5, 1975. 97. Antitussive Drugs... IL Bronchopulmonaryeffectsofdextromethorphan~ and doxylamine. D: M. Aviadb, A. Bianchi and J. Drimal. Arch, Int. Pharmacodyn. 216: 216-224, 1975. VII. PULMONARY EMPHYSEMA, PROGESTATIONAL STEROIDS AND TOBACC0(1965-1976) 98. Bronchopulmonaryeffectsy of tobacco and related substances. I.. Broncho- constriction and bronchodilatat5on: influence oflungdenervation, D: M. Aviadoand M... Samanek. Arch. Environ. Health. 11<. 141-151,. 1965. 99. Bronchopulmonary effects of tobacco and related substances. II. Bronchial arterial injections of nicotine and histamine. M. Samanek and D. M. Aviad'o. Arch. Environ. Health. 11: 152-159, 1965. 100. Bronchopclmonary effects of tobacco and related substances. IIS. Axon reflexes elicited f>-om the visceral pleura. Mi Sarnanek, D. M. Aviadb andIG. W''. Peskin. Arch. Environ. Health. 11: 160-166, 1965, ' I k !
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D_,^it. PaOc 11 1101. Bronchopulmonery effects of tobaceoand~ relatedsubstanees. IV. $ronchial vascular and bronchomotor responses;, their suegesced defense function. M. Samanekand: D. M. A~,iado. Arch. Environ... Health. 11: 167-176, 1965. 102. Cardiopulmonaryeffrets oft'obacco andrelatedd sutistances,. 11. The release of histamine during i:Ltialtition of cigarette s:noke and ancxemia in.the heart-lung and intact dog preparation. D. M'. Aviad.o~, M. Sarnanek and,L.E. Folle. Arch. Environ. Health. 1Z': 705-7:11, 1966. 103. Cardiopulmona.ryeffe.cts of tobacco and related substances. 11.Coro- nary vascular effects of: cigarette smoke and nicotine. L. E. Folle, M. Sarnanek.and.D.ML Aviado... Arch. Er.viio^.. Health... iZ; 7.1Z- 716, 1966. 104. Cardiopuimonaryeffe.ct.s of tobacco and related substances. ,'.Il: Pul- monaryvascular effects.ofcigarettesmoke and ni~cotine. M. Samanek.k and D. M. Aviado. Arch, Environ. He.altn. 12: 7L7-724, 1966. 105.Pulmonary effects of tobac.coand.relate.do substances. 1. °clmonaryeompliance and resistance~in the anesthetized dog. P,M. Aviado~and F. Palecek; Arcli: Environ, Health. 15: 187-193, 1967. 106. Pulmonary effects of tobacco and related substances. Il. Comparative effects of cigareY.ee smoke, nicotineand.histamineon the anesthetized cat... F. Palecek and D:.M. Aviado. Arch. Environ. Heal.h. 15: 194- 203, 1967. 107. Pulrnonarvv effects.oftobacmand related substances. 111. lnhibitionn ofi synthesis of histamsnein various species. F.. Palecek... M. Oskoui and D M. Aviadc. Arch. Environ. Health. 115: Z04-213', 196;. 108. Emphysema iir immature rats condition prodticed by, tracheal con- strictEon andpapain.F. Palecek„ M.Palecekova.andD. M'. Aviado. Arch. Environ. Health. 15: 332-342„ 1967. 1109. Preventionof~pulmonaryemphysema in.rats byprogesterone. H.It'o Ther. 161: 1'97 204; 1968, and D. M. Aviado. J. Pharmacol. Exp. 1104 Puimonaryemphys.ema and cigarett'ee smoke. Eaperimentaliindu.ction~~ and use of bronchodilators in rats. H. Ito and D:,M. AviadD. Arch. Environ. Health. 16:. 865-870. 1968. 111. Differences in the effects oLinhalation of; sulfur dioxide and cigarette smoke. Y. W. Cho. M. Samanek and D..M. Aviado. Arch. Environ. Health. 16: 651-655, 1968. 1112. Ca rov smok Er *ir 113', Oral Aviac 1969: 114. Horn their Emri 115, Horn Shor 116. 1'dorn anes Heal 117. Ciga dilal Aviz 20: 118: Pha. D.1. 197, 1.19, Pha adr Pr.a 120. Cai rat; I2~1," Exl~, In: Ne 122, + Th 10
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211 D :4:4. Page 12 112... Carotid receptors and br.onchornotor responses. Effects of cigarette smoke, lobeline, and cyanide. A. M. Klidee and D:.M. Aviado. Arch. Enviran: Health. 17: 65-70, 1968. 113. Oral progestagens and experimental pulmonary emphysema. D: M. Aviadb and! G. R. Mc.Kinney.Pharrna.col. Res. Commun. 1: 2&3-287, 1969: 114., Hormonesand:pulmonary.effects oftobacco... 1. Corticosteroids and their antiasthmatic action. D. M. Aviado and L.. R. Carilio.. Ar.cn6 Environ. Health. 1B: 925-933, 1969. 115. Hormoness and pulmonary effects of t'obacco. IIl Progesterone. S. R. Shore and! D. ML Aviado. Arch. Environ. Health. 19: 59-69i 1969. 116. Hormones and pultnonary effects of tobacco., 111. Corticosteroids in anesthetized dogs... L..R. Carrillo.and D. M. Aviado. Arch, En.,-iron.. Health. 21; 149-153, 1970. 117. Cigarette smoke and pulmonary emphysema. Influence of bron cho- dilatorsand biogenic amimess inerperirnental induction,in~ rat's. D. M. Aviado, C. Sa.dhvongviv.ad:and L. R. Carrillo. Arch. Enviro n.. 1-?ealth. 20: 463-487, 1970: 118'. Pharmacological significanc.e of biogenic amines.in the lungs: histamine. D. M. Aviado and C. Sadavongvivad. Br., J. Pharmacol. 38: 366-373, 1970. U19.. Pharmacologi~call significance of bioggnic amines in the lungs: nor- adzenalineand dopamine. D. M. Aviado and C..Sadavongvivad.. Br. J.Pharmacol. 38: 374-385, 1i970 120. Cardiopulmonary effects of progestational a2ents in emphyserr.atous rats. T. Inoh and D.M. Aviado. Chest. 59:' 659-666, 19711. 121. x Experimental pulmonary emphysema and progesterone. D. ML Aviado. In: Pulmonar:y Emphysemaand.Proteolysis., Academic. Press, Inc.., New York, pp, 419-420, 1972. 122. * Thce casc aba....,. tobacco .s ...,.' c...sed.. D..... A:.ado.. -- - Health. 10: 11-5, 1974. ' 1123. Functionaland:bioche.mical effects on the lungfollowing,inhalation ofeigarette smoke andlconstituents. I. High- and low-nicotine cigarettes in mice. D. M. Aviado~and.T. Vdatanabe.: Toxiccl. Appl. P.`.armecol. 30: 185-200, 1974. M P @
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212 124. Functionaliandlbioche.micaleffects on the lung,following inhalation;of cigarette smoke and constituents. IIL Skatole„ acrole:in ar.d actealt',ehyde, T. Watanabe and D: M. Aviado: Toxicoh ApoL Pharmecof. 30: 201- 209, 1974. 12~5. Functional and.biochernical effects on the lung,following inhalationm.ofcigarettesmokeand constituents. :IQ. Roleof.b.iogenic amines,, D. M. Aviado. Toxicol. Auol., Pharmacol'. 35. 403-412, 1976. 126..* Biogenic amines, cigarette smoke andlpultnonaryemphysema. D. M. vuY.~ and 127. * The p patho,7 Editec pp. 1 ' Aviado.In:' Air Poiiutiion and the LunE.. Edited by E..F. Aharouson„ 128. Myoca A.Ben-IDavid and M. A. Klinberg, John.Wileyand Sons, New York, D.M, pp. 107-113, 1976, 129. Studie Y. W. Pharn 130. The m activit Cho, 1 1b7-li 131s= Physic Aviadc. Charle 132. * Ader,ot Traum, 133. Acute Arch. 134. * ~ Contro CardioNew Y- 135.* Ptilmo: Cardio Stratto 13o. • Drugs Aviado Inc., 1
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213 DMA~ Page. 14 VIII, CIR'CULATOR'Y' SHOCK„ PULMONARY INSUFFICIENCY and PERIPHERAL VASODILATORS (i 1905 - 1i97b ) 1Z7: *Thepuimonarycirculation with special reference to.it's ro1ein the pathogenesisof shock. D.M. Aviado. In: Shock and Hti-potension. Edited by. L..C.. Mills and J. H'. Moye.r.Grune and Stratron, New York, pp. 150-15b'y 1905. 1z8: Myocardiall metabolic changess during acute hemorrhage. Y. W.. Cho,. D.M'. Aviado and S. Bellet. Angiology~ 116:: 532-537, 1965. 129. Studies of my,ocardial oxidativeenzymesdurino histaminic shock. Y. W. Cho, J. Theogaraji D. M'. Aviado and S. Bellet. _Arch._InU. Pharmacodtim. 158: 314-323, 11965. 130. The myocardial', sucoino-oxidase and myosin adenosinetriphosphatase activites after coronary arderial infusion of' histamine in dogs. Y. W. Cho, L.. Bonet and.D.1J1. Aviado. Arc.h. Iht.Pharmacodyn. lo1:. 167-173', 1966. 13 1.= Physiology of the pulmonary and bronchialvasculor systems. D.M. Aviado. In: Vascular IDiseaseso.f'theL_un~o. EditedbyH.A. Lyons, Charles C. Thomas, Springfield, pp. 13-24', 19oY. 132. * Ader,osine diphosphate and vasoa.ctivesubstances. D. M. Av.iado. J. Trauma. 8: 880i-884„ 1968. 133. Acute effects of air pollutants on the lungs. D. M. Aviado„ and H. Salem. Arch. Fnvizon.Health, lbt 9J3-907, 19b8- 134.* Controll of pulmonary circulation. D:M. Aviado. lnt Clinic.al. Cardio ulmonanyFhy,siolo^}•. Edit'or, B. L. Gordon, Grune andStratton,. New York„ pp . 305-31i3, 1'909: 135. W Pulmonary pharmacologics. D. M. Aviadoand Y. W. Cho. Ih:` Clinical CardiMulmon_aUE_hy_siol_o-z,)L! Editor,, B. L. Gordon, Grune and Stratton, New York, pp. 714-727„ 11969. 13o. • Drugs for the therapy of pulmonary, disord'ers. T. P. Ptus.sand D..M. Aviado. In: Annu.al.R'~pnrtsin Medicinal Chernist~r~ Academic Press Inc., New York, pp 55-b2„ 1i970. ^-- - ff p M 9 0 0 0
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214 DMA Page 15 137. W Pharmacologic principles in the treatment of acute respiratory in- 5?min.Dr ~~ sufffic.iency. L. V. Balcazo,, Jr. and D:.bt.. Aviado. Treat. 3 (3): 241-248, 1973: DiM. Aviado and L. V. Bal~azo, Jr. J. F}:armacol.-Exa. Ther. 189: 157-166, 1974. - 139~ * ' Peripneral vasodilators. D. M.. Aviado: Druo L-if. J. 10: 36-40, 1976. 138: PYevention of acute pul:nonaryinsufLici~encyby, eriodictyoi'. 140. A compar.atives.tudy between tnecardiovascul'ar effects of cetiedil, a newvasodilator, and papaverine andiarninophylline. J.A'. S:ma3n, and D:1vS. Aviado. Ji. Pnarmacol._Ex_p. Tncr. 195: 14o-180, 1976.
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215 D:4A Page 16 IX. CORONARY VASODULATORS ANDCARDIOAC'D1VE AGE\TS(1966-1975) 141. The cardiopulmonary effe.cts: of quinidineandiprocainamide. L. E. Folle and D. M. Aviado. J. Pharmacol. Exp. Ther. 154: 92-102, 1966. 142. The cardiopulmonary effects of'a wuinazoline (MJ 1988):. Cardiac stimulant, pulmonary vasodilator and br~onehodilator. D: M.Av.iado, L.E. Folle and!J. Pisanty. J. Pharmacol. Exp. Then 155c 76-83, 1967. 143. The influence of anewa adrenergic beta receptor (MJi 1:999),blockingdrugon the pulrnonaryy circulation.. D:M.. Aviado, L.E. Follwand JL Pisanty. Arch. Int. Pharmacodyn. 168: 323-338, 1967. 144. Bronchopulmonary effects of:digitalis in the anesthetized dog. ' Y.. Marco, C. D. Park and D. M. Aviado. Dis. Che st 54: : 437-444„ 1968: . 145. Cardiopul4nonary effects of glycer,yl tr,initYate and isosorbide dinitrate. D. M. Aviado, L.E. Follp,and S. Bellet. Cardiologia 52: 287-303, 1'968'. 146. Coronary vasodilators on myocardial oxygen consumption and ammonia prodtrctiori';' D. M. Aviado, H. Ito, Y. W. Choand.S. Bellet. Czrdiologia.. 53: 27-46, 1968. 147. Bronchopulmonary effects of'pentaerythritylitetramitrate and isopro- terenol. D: M. Aviado, T. lCshirnoto and'H. J. Kneidinger. J. Pharmaco' Exp._Ther. 165:' 27&-285, 1969. 148: Stimulation of adrenergic beta receptors by halothane and its ant'agonism by two neww drugs. A. M. Klide, M. Penna and. D. M. Aviado. Anesth. Analg_. 48: 58-65, 1969- 149. Comparative effect's of digoxin and proscillaridin in the heart-lung prep- ~ aration. H, Ito, Y. W. Cho and D. M. Aviado. Dis. Chest. ' 56': 37-42, 1969. 150. Pharmacolbgy of a new antianginall drug: perhexiline. I. Coronary circulation andd myocardial metaboli!sm. Y. W. Cho, M. Belej and D. M. Aviado. Chest. 58: 577-581, 1970. 15L. * Pharmacology of aa ne.v antianginall drug: perhexiline.. LI. Heart ratee and transmembrane potential of cardiac tissue. S. Matsuo, Y.W. Cho and D. M. Aviado. Chest. 58: 581-585, 1970. 0 W 0 LJ,A ~
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216 DM_2 Page 17 152. Pharmacology of a new antianginal drug: perhexiline. III: Broacho- pulmonary system in thee dog and humans. O: Feinsilvery Y. W. Cho and D.M. Aviado. Chest. 58: 558-561, 1970. 153. .Effects of oxprenolol on coronary circulation and' cardiac metabolSsm. J. Drimal and D. M. Aviado. J. Pharmacol. Ezp. Ther. 176 . 312- 319, 1971. 154. Cardiac effects of sodivm selenite. D.M. Aviadb, J. Driknal, T. Watanabe and P.M. Lish. Cardiology'.• 60, "113-120, 1975. '.,.., ,
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217 DMA Page 1'8 X. PHARMACOLOGY and TOXICITY OF NEW'ANTIMALAP,'IAL DRUGS (19b7-1972), 355. Pathologic physiolbgy and chemotherapy of Plasmodium berphei. I. Suppression of parasiternia by sulfonos and sulfonamides in mice. D.M. Aviado. Exp. ParasitoL 20: 88-97, 1967. 15o. Pathologic physiology and cnernotherapy of Plasmodium berghei. II. Oxyhemoglobin dissociation curve in rnice infected wikh chlbroquine- sensitive and resistant strains. F. Palecek, Ml Palecekova and: D.M, Aviado. Exp. Parasitol. 21: Ib-30, 19o7. 157. Patnolbgic physiology and chemoty erapyrot Plasmodium ber£hei. III. Renal function in rat's infected with Plasmodium berRhei. T. Kisnimoto„ M6 Oskoui'and D+M. Aviado. Exp. Parasitol. 22: 160-177, 1968. 1158. Pathologic physiology and chemotherapy, of Plasmodium benQhei. IV. Influence of chloroquine on oxygen uptake of red blood cells infected with sensitive or resistant strains. Y. W. Cho and D. M. Aviado. .Exp. Parasit'ol. 23: 143-150, 1908. 159. Pathologic physiology and chemotherapy ofiPlasrnodium ber~hei. V. Suppression of parasiternia, diuresis, and cardiac depression by pteridiaes. D.M. Aviado. B. Bruoler and J. Bellet. Exp. Parasitbl. 23: 294-302, 19ots. lb0~ Pathologic physiology, and chemotherapyofPlasmodiumberRhei. VI. Mechanical properties and nistological features of the lung. C. Sadavongvivad and D. M. Aviado. Exp. Phrasitol. 24: 313'- 32b, 1909. lol. Phthologic physiology and chemotherapy of Plasmodium berpheiL VII! Electrocardiogram in mice treated with quinidine and guanidines (ICI 3349! and WR 81, 844). M. A. SiUver and: D. M. Aviado. , E>.~. Parasitol. 24:' 152-1o2, 19b9- l02'. Pathologic physiology and chemotherapy, of Plasmodium ber~hei: VIII. Liver enzymes and 6he inflhence of hexacnlbroparaxylene (WR 17, 206). D. M. Aviado, Y. W'. Cho and' J. M. Smith. Exp_ Parasitol. 25: 283-290, 19p9. B 0 I g 01 A u ~ ®
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218 D1J.A Pagc 19. 114. 103. . Pathologic physiology and ehern,the.rapy of Plas_modiumberPh~i DC. Gastricc secretion~and! tnee influence of 1-a-inocyclopentane carboxylic acid (WR14, 9.97), or Cyoleucinc). D. M. Aviado and H. A. Reutter, Jr. Exp. Par asitol, 26. 314-32Z, 1'9b9• 175. P 1b4. of PlasmodSum ber ng ei. h siolo Patholo ic and ehernothera m p y. py g dy, 24 X. Pulmonary edemaand napntnoquinones (1'r R2b, 04'1and W.R49, 808). D: M. Aviado and! P. J. Cambar. Exp. _Parasitol. 26: 176. P; 354'-3b8, 19b8. ]b5. Antimal6rial and'antiarrliythmic activity of plant ext'racts. I. W Cinchona and quininee in Pla_srn_odSum bcrgnei in immature rats. D.M. 177. Co Aviado, R.. R'osen,. H. Dacanay and S. Plotkin. Med'. Exp. T 19: 79-94, 1909• . 15 ]bo. Antimalariatand~antiar~.rhyttimicl a~ctivi~ty~of'.plant extracts.~ 2. Acid'~ 178. Cc extracts~of~plants. D~.M. Aviado and H.~ Reutter. Med. E?cp. 19:'~. an 95-100; 19b9: lb7_* Chemotherapy of Plasmod[um ber hei. Including bibliography of 179 Be I ' . nf P1 as.modium_ber.phei. Parasitological Review. D. Ml Aviado. E~.-n. Parasitoi. 25" 399-482', 1969. on 103. Pnarmacoiogy of new antimalarial dr~ugs. IL Sulfones. D..M. Aviad'o- 180 an C , In:.. Mode_of Action of_Anti-Parasitic.Dr_ugs (Proceedinos of tne 3rd . a ch: International Pharmacological Meetings, July 24-30, 19bb~ Vol.. 1,.. Ca Pergamon Press,, New York,, pp. 51'-0~!', 19o8- . - . 18'I. Ca 109.. .Pharmacology of new antimalarial drugs. II. RG12,. sodium.antimonym me salt of astiban and kethoxal-bis: tniosemicarbazone. D.M.Aviado.,. Ph V. Marco and D. Weed- Chemotherapy. 13: 339-3551 1958. 182. Ca 170. Pharmacology of newantirnalariaLdruas. III. Sulfonamides andd trimethoprim. D. M. Aviadoj G. Singh and R. Berkely. Chemo'_herapy. miI 19b9. - 14: 37-53 mi. 101. , Pnarmacology of new antimalarial drugs. IV. A piperazine which 183. D.: Ca: exerts an unusua) type of adrenergicblockade. Pl J. Cambar and D.M. Aviado. Arch. Iht. Pharmacodyn. 1t93; 10t-12b, 1970. aci R . 486' 172. Pharmacologyof new anlimnlacial drugs. Two quinolinemetna3ols. D. M. Aviado,and M. 13'elej. Pharnnaco~ln _,Y. 3: 257-272, 1970. 184. Car 173. . Pharmacology of newv antimalarial dru.,s:tnree guanylnydrazone.s. a r D.1 R.. Rui~zand D. M- Aviado. PHarrnacolot;y,. 4: 45-62,. 1970.
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219 D1A.Page 20 11,1. . Pharmacodynamic effects of ttiee dSformyl deriv.ative of diaminodiphenyl suifone (DDS).D: M.Aviado,. G. Marroquin and S. R.Shore. lnt. J'~ Leprosy. 3b: 43Z'-441, 1902. 175. Pharmacology ofmetachloridine;;with~special reference to it's anti~ malarial activity. D. M"Aviadb and A. Ike. Chemotlierapy. l 13':. 289- 302', 1968. 176. Pharmocologyrofnaphthoquinones:y with special reference.to the anti- malarial activity of lapinone (WP. 26, 041). D.lti.. Aviado and D:H'. Will. Am. J. Trop. Med. Hyg. 18t 188-198; 1969. 177. Comparativee toxicityofchloroguanide andnitroguanil. D. M.. Aviado, T. Inoh and Y. W. Cho. Toxicol Appl. PharmacoL 13; 2Z8'-241, 1968. 178. Comparativtoxicity.of-chloroquine.andbis /(chloro-7"-quinolyl-4:")~ amino-2'propyl/-1., 4-piperazine (WR: 3863)'; D. M: Aviado.and'S.. Bel.let. ToxicolL Appl. PharmacoL 15: 331-344, 1969. 179. Influence of chloroquine and phenanthrene methanols (}9R'33„063) on content of biogenic amines in themousellrng. C. Sadavongvivad and D. M. Aviado. Mi1. Med. 134: 1i106-1118', 1969. 180. Cardiopulmonary effects: of antinialarial drugs. I. 4-aminoquiuolines: chloroquine quinetholate. D: M. Aviado, C. Sadavongvivad and P. Cambar. Toxicol'. Appl. Pharmacol'. 17: 107-1:17, 1970. 181. Cardiopulmonary effects ofantimalarial drugs. I1.Phenanthrene- methanols. R. Ruiz, M. Belej and D.ML Aviado. ToxicoL. Appl. Pharmacol. 17: 118-129, 119706 18Z.. Cardiopulmonary effect's of ant'imalarial drugs. IIL Diaminopyri- midines: Trimethoprim (WR 5949) and 5-piperonyl-2,4-diaminopyri- rnidine (YR 40, 070). S. MaUsuo; R. Ruiz, J. Smith, Jr., and D. M. Aviado. Toxicol. Appl. Pharmacol. 17: 130-150„ 11970. 183. Cardiopulmonary effects of antimalarial drugs. IV. Tereplithalic acid,d and its dihydroxamine derivative (WR'74., 106). E.O. Grigas, R- Ruiz and D~ M. Aviado.. Toxieol. Appl. Pharmacol. 18;: 469- 486y 1971. 184. Cardiopulrnonary effects of' antimalarial drugs. V. Cycloguanil and a new triazine compound (WR' 99, 662). R.. Riiie, E. 0. Grigas and D+M. Aviado. Toxicol. Appl. Pharmacol, 18: 487-497, 1971. 8
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220 DYJ.fc Page 21 185. Cardiopultnonary cffccts of antima1hrial drugs. VI. Adenoxine, XI. .. quinacrine and primaquine. S. Bass and Di M. Aviado. Tokicol. Appl. Pharmacol. 21: 464-481, 1972s 186. Cardiopulmonary, effects of antimalarial drugs. VII: Coronary vascular effects of pyridoquinolines. M. A. Rarnirez, J. Drimal 187, , Ca In: and ID. M. Aviado. Toxicol. Appl'. Pharmacol. 21: 482-494, 1972. To Pa ]68. , Kr. Av. Ed Pu' D. 189.* To. An Re 29: 190. * To: Ed' ?91, Z;o. 5 y: A. 1192. To sy! . S.. 34" 193, To w 6y: tor To ]94. To sy: anc 195. . To ~ sy, Be 34-12L C
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221 D14A Page i XIt INHALATIONAL TOXICITY OF AEROSOL PROPELLANTS AND SOLVENTS>(1971-, ) 187..„ Cardiopulmonaryy effects of fluorocarbon compounds. D. M. Aviado. In: Proceedinfis of the 2nd Annual Conference on Environmentz1 'Doxicology. Aerospace Medical Research Laboratory, Wright- Patterson Air Force Base, Ohio, pp. 31-39, 1971. Kratschmer reflex.induced byinhalhtio- olaerosol propellants. D.151~ Aviado. In: Conference on Toxic Hazards of Halocarbon Propellants. Edited'byG.E.Thompson,.. Dept'. of }lealth,.. Education,., and Welfare, Public Health Service, Foodland Drug Administration, Washington, D. C., pp. 63-77, 1972. 15I'. # Toxicity of propellants. D: M. Aviado. In: Proceedin.-s of the 4th Annual Conference on Envirorimental Toxicolbg y. Aerospace Medical Research Laboratory, Wrig}tt-Patterson Air Force Base, Ohio, pp. 291-329, 1973.. 191. Toxicity of; propellants. D. M. Aviado. In: Progre ss in Drug Re search. Edited'by E. Jucker, Birkhauser Verlag, Basel. 18: 365-39$, 1974. Toxicity of aerosol propellants on the respiratory and circulatory systems. 1. Cardiac arrhythmia in the mouse. D. M. Aviado and M. A. Belej. ToxicoloRy. 2: 31-42, 11974. 192. Toxicity of aerosol propellants on the respiratory and circulatory systems. II. Respiratory and bronchopullnonary effects in the rat. S. A, Friedman, M. Cammarato and D: M. Aviado. Toxicology. 1: 345-355, 1973. 193. Toxicity of aerosol propelIlants on the respiratory and circulatory systems. III. Influence of bronchopulmonary lesion on cardio-pulmonary toxicity in the mouse. R. S. Brody, T. Watanabe and Dl M. Aviado. ToxicoloRy. 2: 173-184, 1974. 194. 195. Toxicity of aerosol propellants in the respiratory and circulatory systems. IV. Cardiotoxicity in the monkey, M.A. Belej, D1G. Smith and D. M. Aviado+ Toxdcology. 2: 381-395, 1974. Toxicity of aerosol propellants in the respiratory and'circulatorY systems. V. Ventricular function in the dog. D:M. Aviado and M.A. Belej. Toxicology. 3: 79'-86,, 1975. I 3i-12.1 OO - 78.- 18
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222 Dt.1f. Pace }~ 196. Toxicity ofaerosol propelllant's in the respiratory and circulatory ~ systcrns. VI.. Influence of cardiac and pulmonary vascular lesions in the rat. R. E. Doherty and D. M. Aviadb. Toxicolof;y. 3: 213-224„ 1975. 197. f Toxikit'y of aerosol propellants in the respiratory and circulatory systems. VII. Influenc.eofpulmonaryemphyse:ma and anesthesia in~ the rat. T;, Watanabe and D.M.. Aviado.. Toxicology. 3.:225-Z,10, 1975. 198.. Toxicity of aerosol propellantsin the respiTatory and circulatory . systems. VIII. Respiration and circulation in primates. D. M. Aviado . and D. G. Smith. Toxicology. 3: 24'1-252, 1975. 199. Toxicity of aerosol propellants in the respiratory and circuPatoryy systems. IX. Summaryof'the most toxic: tr~ichloroPluoromethane (FC 11)i D. M. Aviado. Tor~. 3': 311-219, 1975. 200. Toxicity of aerosol propellants in,the respiratory,and circulatory systems, X. P1-oposedclassification . D. M. Aviado. Toxicolo~y_ + ~ 3: 321-332, 1975, ft 201.~x~ Toxicity~of aerosols. D.M~~. Aviado. J.~ Clin. P}ia~rmacol.~. 15: 86 ~•. - ~ 10§s 1975. ,. _. ,'i 202. Cardiopulmonary toxicity of propellants for aerosols. ML A. Beiej and D. M. Aviado. J. Clin. Pharmacoi. 15: 105-115, 1975. 203. Five fluorocarbons for administration of aerosol bronchodilators. D. M. Aviado and J. Drimal. J. Clin. Pharmacol. 15: 1Q6-128, 1975. 204. Hemodynamic effects of aerosol propellants. L Cardiac depression in the dog. J. A. Simaan and D. Ml Aviado. Toxicology,. 5: 127- 13$, 1975. 2; 205. Hcmodymamic: effects of aerosol propellants. II. Pulhnonary circula- '' ' tion in the dog.. J.A. 5imaan and D. M. Aviado: Toxicology., 5: 139- 146, 1975. 206. Hemodynamic effects of aerosol propellants. III. Vascularresistance 208.* L a 1 209'.* L 9 1 210.* C n 1 211.* B: HI in,theeanine hind limba J. A. Simaan and D. M. Aviado. Toxicology. 5: 287-295, 1975.
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223 XIiI. CLINICAL PHA&MACOLOGY (',1'975- 207.* Regulation of bronchomotor tone during anesthesia. D. M. Aviado_ Anesthesiology. 42:68-8Q, 1975_ 208.* Drug action, reaction and interaction (DARI). I. Cardiac arrhythmias. D. M'. Aviado and H. Salem. J. Clin. Pharmacc 15: 477-485, 1975. 209.* Drug action, reaction and interaction (DARI). II- Iatro- genic cardiopathies. D. M. Aviado. J. Clin. Pharnacol. 15: 641-655, 1975. 210.* Drug action, reaction, and interaction (DARI). III. Dopa- mine for Endotoxi~c shock. J. Clin. Pharmacol. 16: 88-98, 1976. 211.* Bronchodilator and~antiesthmatic drugs. D. M_ Aviado and H. Salem. In: Bronchial Asthma. Edited by E. B. Weiss and M. S. Segal, Little Brown and Company, Boston, 715- 725, 1976. 212. Inosime as a cardiotoni~c agent that reverses adrenergic beta blockade. A. Juh'asz-Nagy and D. M. Aviado. J1. Pharmacol, and Experimental Therapeuti'cs._ 202: 683- 695, 1977. 213. Pharmacologie du tonus bronchommoteur au cours de 1'' anesthesie. D~ M. Aviado. Ann. Anesth. Franc. 18: 569- 573, 1977. 214. Preclini!cal pharmacology and toxicology of halogenated solvents and propellants. Edited'by C. W. Sharp and M. L. Brehm., National Institute of Drug Abuse. Review of Inhalants: Euphoria to Dysfunction. Chapter 10. Monograph 15. 164-184, 1977. 215. Adrenergic agents in,bronchi:al asthma,, emphasizing, undesirable reactions. In: Status Asthmaticus. Edited by E. B.. Weiss, University. Park Press, Balti~more.,215-223,, 1978. 0 N I ~ 0
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224 ~ a K-) STATE1fENT'OF LEER. NYLANDER„ PR.D.. 3740 Morse Avern.e . . Ch ca94aLitireotrwro©d); , II Iinois:60645 (312)677-0450 ' Members of theChicago. CityCouncil--b7yname is LeeNylandkrand I am Vice-Pr~esidhnt of~ Chemical 9ervicesfor Polytechnic,. Inc. I have a doctorate in.inorganic.ehemistry and special training in the areas of meteorology and air pollution conirol... A listing of myprofes:sional specialities and.association memberships can be found in t'~heresume which~is att'~ached to this statement. Some ofthe.recent~ literature on.the publi.c'srnoking question centers.on cartiom monoxideas- the constituent of tobacco smoke that presents a potential health~hazard to nonsmokers. Polytechnic was retained byy t~heIllinoi~s Association of Tobacco and~Candy. Distrihu- torsto evalluaUeindoor and outdoor levels oficarbonrnonoxideactuallypresen.t im andd imrmediatel~y, outside of nine indoor public pliacesttiat permit smoking. All the public places arelocatiedlin the City of Chicap,o.and the arrangements for testing.were made through the cooperation~oft~heChicago andiIllinois Restaurant _ Association'and.theChicago Hotel and. Notel Association. - Continued - of in suli and has The sam for ilnd car mai for are R'ou Sam ran eit sit cou 6:0 wer con usi Ene mil
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225 F e 1645 t, 1450 C C~F S -Z_ Polyteehnic, Inc., is a Chicago basedieonsulting.firm.consistingg o.b engineers andd chemists servingindustry, management, and government i'n the areas of environment'~al engineering.and testing, chemical con- suliting,and analysis, hazards.and safetyengineeringy and accident and forensic investigation. The Chemical Serv.icesDivision of Polytechnic hasbeen~performingenv.ironmentaL testing for t,helast.seven years.. Theseservi~ceshave included OSHA airquaLi2y evaluations, source sampling,., ambient air surcveys„ and the development.ofianalyticad methods for air pollution.. These projects:have been sponsored by both privateindhstry, and.muni~cipal, state,, and'.federal agencies... The purpose of this project.was to evaluate.the actual 1'~evelsofcarbon monoxide present in the dining areas of four restaurants, the main lobbies oftihree.hotel's, and thee waiting.areas at.two terminals for public transportation. The names andladdresses for these locations are listed in Table1.. Sampling.timeswere scheduled such t'~hat.theyt wuuldd be representative: of normal'e usebythe public. For example, sampling was performedd at either lunch~or dinner time foreachrestau- rant.when they were full or nearly full. Hotel lobbies were sampled either in the.late morning or e.arlyafternoon, while people were sitting in and wal~kingthrou.gh them. Sampling at the airline ti~ckett counter andiat the bus terminal was performed'betw•een 5~:00P... M. to. 6:00 P. M., and. 4:00'P. M. to~5.:00 P. M'., respectively, when people weree waiting in lines and walking.throughithe open areas.. Both indoor and outidoor carbon monoxide concentrations were continuouslry.y monitoredd for a total of thirty minutes at each.loeati~on using.portable Ecolyzer carbon monoxidemonit'~orsmanu.fja:ct'ured by. Energetics, Inc. These instruments have a range.of 0 to 100:parts per million (ppm) for the measurement of carbon monoxide. - Continued - M ®
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226 ~' :. -3- Toinsure accuracy.,,both.instrumentswere.calibrated with the same .~' 50 part per million carbon monoxide span~gas and zeroed iirvmediateiy. - ~4 Ir before being used:ar.each area tested. Both instruments were also te equlppediwith a continuous strip chartt recorder so that time.averaged and . sh instantaneous concentrations could.be measured'. ' mi Indoor locations were di~vided! into approximately.fourequaly OS areas at seven of the locations and three equal areas at two of the ho, lbcatiions to evaluate spacial variationsinicarbon monoxide levels. al Sampl~ing.times for thesampling,areas.were seven to eight.minutes ` 35 for the locations divided into four areas and'tenmihut'es:for the ond locations separated into~three areas, respect~ively. The airinlet. '~. mon for the indoorinstrumenti was locat':ed.atapproximatelyhead level s ta for a seated adult so that carbon monoxide could be measured in the bur i t proper resp ory zone. ra Out~doorconcentratio ns wene.measured justoutsi~de the.main for entrance of eachibui'llding. at a he ight of approximately.f~ivefeet sbo abovegrounde level. Iindoo r and o utdoor instrume.nts.were calibrated `ti exc, at.t'~hebegining of each sampling period with the samespan gas, soo tim, that comparisons could be made between instruments.., ~ be ' Air quality,st~andards for carbon monoxide have been set by, the '2:, a. Occupational Safetyy and Health Administration to,protect.workers, and indc by the Federal Environmental Protection Agencyy to-protect the general leve public. The OSHA.standard limits carbon monoxilde exposure to an `i F.' for average value of 500 parts per millionforan.eight-hourtime periodl. {The.pri'maryambient'air qual'it.yy standards for outdoor air limit average.ca.rbon monoxide levels to 35,paits per million f~oranyone-houraveraging time, and 9 parts per million for any.e.ight-hour averaging time. - Continued - Atita.
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227 Tlie resu.ltsof the.sampling survey are shown in Table 2. Indoor 30-minute time averaged carbon monoxide levels observed for all Locat'~ions ranged between 2 to6'parts per million,, whileshort.term, peak concentrations rangedi between 2 to 20 parts per million.. These values are we1Q belowthose considered safe byCSHA for occupati~onal exposure to.carbon monoxide overr an eight- hour work day., The observed average carbon monoxide levels are also well below t'~heEPAprimaryambient air quali2yy standard of 35 parts per million-veraged.over aa one-hour period. Moreover, on]y one.indoorsampling area out of thirty-four had.a.carbon monoxide measurement that'~ exceeded t'~heeight-hour ambient air standard of 9 ppm and.t'hiswas due t'othe use of a.portablie cookingtarner nearthesampliing,area. Outdoor 30-minutie timeaveragedicarbon monoxide levels observed for alil locations rangedibetween 1 to 188 parts per mil'~lion,with short term maximum~concentrationsaveraged over 3}.mi'nutesonce exceeding 40 part'~s per million. Based upon observat.ions.made at'~ theti~me of sampling, these higherlevels,of carbon monoxide appear to be the.resulit of emissions from motor vehicles. In summary, average carbonmonoxi.deconcentrations at all of thee indbor locat'~ions wheree smokingi'~s permitted were found not'~ to.exceed levels considered to be safe for~ occupational exposure.by OSHA,,.and for the.e general public by the EPA. Respectfully submitted~,~. POLYTECHNIC, IN Lee R.. Nylander„ Ph.D. Vice President-Chemical Services
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228 TABLE 1 SAMPLING LOCATIONS RESTAURANTS W'ALGREENS RESTAURANT llERCHANDI SE MART PLAZA SEVEN CONTINENTS RESTAURANT RESTAURANT BUILDING O'HARE INTERNATIONAL AIRPORT NICK'S'FISH MARKET 1ST NATIONAL BANK PLAZA . LA CHEMINEE1161 NORTHlDEARBORN HOTEL LOBBIES DRAKE HOTEL EAST LAKE SHORE DRIVE & NORTH MICHIGAN AVENUE PALMER HOUSE STATE AND MONROE BDSMARK HOTEL 171 WEST RANDOLPH PUBLIC WAITING'AREAS UNITED AIRLINES TICKET COUNTER & BOARDING AREA O"HARE INTERNATIONAL AIRPORT GREYHOUND BUS TERMINAL CLARK & RANDOLPH F ' ly,:5._,iCJSr~ LOCA 6'ALG CA 7-C0 DI NICK f.fA R ROO LA C RE DR1K biA PAL'3 f.1A BISnI MA O'RA TICh. & BC GRFY' TE
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229 TABLE 2 SUhIMARY. OF SA\IPLl'NGIDATA INSIDE CO)~, PPM OUiTSTDE (;CO):, PPM I 30 DULN. 3'~~. MINUTE AYERAGE, 30 MIN. 3j'. pIINUTE AVERAGE~ I QU;'ITO:; AVERAGE 6lAPi~IMUM1f~. i bIINIF1IIM1t. AVERAGE , p1AXIb!U~-0 ~~, L11C:I~!Ut•I ' .1LGRF;FNS I C:A'FtiTiERIA 7 8 5~ 4: 15~ 2' -COXTI'U~ENTS DI.J~IN~G, 9REA~ 6~~ 7 5 4 5 3 ;IOE:' S~ FISH "^,~R7CET-DIN~I~NG RQ01S' 4 5 2~ 1 3~ 1 ..A~ CtiELR~1I!\i:E, 8 20. 4~ 6 8~ 2: itESTAUR.INT I JR:19iE ROTELV p1.yI'S~ LOBBY' 5~. 6~~ 4 4 6 2~ PALIIER'~ llOUSE~ Dii1I:i'~ LOBBY 5 6 4~. 14 28 . 4~ HISIdiRK HOTFL ~ 2 38 43~ 7~ AlAIN~ LOBBY 2~ 2~ ~ 0' H.ARE~. - U~~. S . TICI:~FT COUNTER 6 6, 5 15 28 8. &~ E0~1RD1NG AREA GREYIIOJND li ~ 8~ 4 8' 23 1 TERMINAL 6 ~ A3 1 I 0 I il1
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230 PROFESSIONAL BAC[iGROL'ND ANU EXPERIE\CE Lee R. P Lee R, Nylander -r. AIRVice.Presildent-Chemical Services ~' POLLUTI( „ Polytechni.c,.Inc. ~~. 3740. West Morse. Ave.nue.kChicaga.(Lincalnwood).,.. Illinois 60645. (312) 677-0450 HOME: 1113 GreenbriarLane„ Northbrook, Illinois 60062~ (:312)~498-5479: EDUCATION: B. A,Chemistry„ Luther Colliege, 1962Ph.D.Chemistry.,, Loyola University, 1972 INDUSTR' HYGIENE SHORTi COURSES.:. "bl0teoroliogyy and Air Pollution Control", I TOD'tIC' AmericanInst.itute of Chemical Engineers, 1973 "StaekSampling"', SP. C. DlcCrone Associates, Inc., 1972 "Hazardous 3iaterialis",, National Hazards: Control. Ins.titute„ 1978 . "Fundamentals of Fire and'Explosion Hazards Ebaluatilon", American Institute of Chenical. Ehgineer:s, 1973' INDUSTiRIAE EMPLOYMENT: - Helene. Curtis Industries - Chermist,, 1963-1964- Iinstitute of Gas.T'echnology- Instrucental.Analq,tical Services - Specialized in infrared and gas chromatographic analysis,,1965-1966- Polytechnic,. Inc. - ChiefChemist,. 1071-1975 Vice Piesident-Chemieal Services, 1975 - Present bSEMBERSIiIPS: American Chemical Soci~t',y Air Polluti~on CbntroLAssociationAmerican Council of.Iindependhnt Laboratories American I'ndustrial Hy.giene.Associ'at'ion, Chicago Section SPECIALITIES:, Air Pollution - ambient, source.andl.inrplant Chemical hazardA. Instrumental and wet metihods ofichemical anallysis - Continued- HAZARDS FiRF. AN ~ EXPLOSI INDUSTR CHE6tICP ANALYSI
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, bhlc 0 I
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232 Curriculum~Vitae of Edvih R.,Fishe.r, M.D. BLO:ioorap',ry,- 1. *' Succeas:ul x:ana^s~_r.[ n: ir:iantiledf arr'ne,in ~enercl~ 1:=spi.a1, ?ti. 29. * Tae p~~ . J. Di~,bis., 17:33::-337, 1930. the Sit 2. •:o?,-rtari[is a"osn ;.^.:a'_vi~~ tnc fea:.le.p^nital Lr:•.cc. A:a. J. CS. 29. A ecnm 6' Gyn. 50:445-.- rabbit 3, Obsen'ations oa~cha.eosinophil ccane 1n mzns a pronosedlzest of c~ccnal 30. Cbserv: eortic_1 func[ior,. ._.,. J. :'ad.. 5ci.. 22.1'-121-132:, 1'5i. 31. P'.etac:I„ 4. Eosinaphiiic gra:ul=a of rib. J. Ti:or..ciic ScrS. 2i:25-29„ 155". bonds. * 5. * firarra.a of t2,e pcricardiu~: L~^r,phc:ic .y-re... Clc¢,. C!ia.: Quart,. 18:12-'_7,. 1951. 32. N acu:e. Shope 6. =P:.icrryliicit:s plas6ica carciccaloP tnncolbn. Clav.. C'_zn. - 33. Purtlier 7,, 217, 1451. 13:21C ~c t;odulcr goiter and.csrcincaa of the thyroiC.. .'~. J, Surg.62:202-2Go, 34'. pancre: Tre ca 1a4-il 1:51, S. ~ BLecdln; duodenal.u?ccr. associated-.i>_heereSellar tcco^ L-i c`.i`_lchcod, - 35. = Glcze_ Castro~n~:raiosy 13.:62o:-ti31, 1951,. 36, * The c: 9. *Tntcacraaisll e?e,:c;r.c,a>. C1_'n:ccantSolo~ir eb;;ervetiur,s. C;zv,.C1in,: ' 37 2:a1-a kTn ocar:.18".L50-270, ti~1 . . . e :oa. 14. r.Conch:c-fi'-n para"p. -iicaa. o," ..,_ orcio. Cs:e=__ 5:521-5'_: 1S'5:, Path, His:o,o-ic and disir'_7e[ia:scvdiasof radiozc'iic ,r,oid.; n th^_C^ihca 33. • Alkali pig, &~. J. :C2d. ,ci. 233.:;07,-511, 19521, tnbule 12. +r-'.:enoolasto~,aof.chac+: ;:ry. A:n... Surg. 135:5+?-Sko, 1952. Anat. 13. :<Coarcca•ic^ u: c:ie abdo^inal' aorta c,-i:h% resulcca '^,;'.cnt=aica...cc?t. 39. hepiro iart, `-.d,. 9~,3-95C' ~952, Physic 14'.. *Linitis plast. ca- incma of the st:o^L^_n,.ztit si:-la ang a.eolc.ic 1esi~cn... Czctroe'•;cercla5y 2Q:59.+325, _._-. 40. The ef Se:r. 15. * Ary1'o;'.$' trnor. of t:'r•z ucina^r, ti1cc.:.cr, J.a'.1:.A, 50:4g-93,1752. 41. • Cytopl 16. *To.e oi inv-cslva. zad inte--t5r.si poly~s.. Clw. Clin.: Q•aarc.1y:G2~-b7', ir. 1'v57. Their cytcpl 17..: :IaliCn=nr loiyns of the .ectn.^.,.t:.d''si5noid: T4:e - ra-y b=s_d on _^r.o!o;ic 42. *The.oce oansiiar~: ecs. S:.G. L'O. 94rG19-623s 11)32'. in the 18' P of 'ali aat the rec:tcm: Follw-cp ob_-ar.• atioas on 27 pa.-ieotc. 43. Livar , _y Posc Gra~!U~te ..ed, 1932.. hepatC'. 19. ^ He~-ng'oo_:icpcc~a: Sc°cial histologi'c aad tissee culture scudiz„ .L.i.uJ'. Patn. 28:u53-5o1, 1:'°-. 44. * The d: speci:: 20. •Thj--i_ nEoplaszs. J...of, iloracic Sur,. 2b:5S c9,.1952. , 261-2/! 21. Paoholn¢'c rha::ges io17.o^r>r.C bila'eral n^-o:~'°ert=yis doos a:drats. 45. 45 * "Psuz,: *S= J.:of: Lab. I:vest. 1:351-363, 1732• . par:: 22.: *.bilticle r..asotUhalial clsts of the peri~coa¢cr.z. A,:.. J.. of Scrg. 47 patno;; ~ Th .. 23. 330, 1952. Tht relation bet:.e=_n benign uleerr and, carcinc.a c° the nco-sch.. ..: e p:P earc4-4 1953 Gastsaecterolo,y22:103-111,. 1932. . 24. Ybo n^?h:otox4c Z..__c.n ofProc. Soc. 03Der. 8:.a1_.. fi 43, ~`F:nip? h 80:452-454,.1952 - 0 Ss:o ' 25. Sir.+:ltaneuus oucurrenee of ti:e thi+rui'ditis actd' papi11ar7c_^cinor..c7 o: 4 * Conbib thyroid. Ca c^rG:57-53, 1,953'. eta 25. * Diffuse p-pi'acnatouspoiyps (vi11e•,:stuaots) oi c= colanc' Pr.tcolagic 50, *Satiz ar,d'clSnlcaid ob::crvt,*_icns. Am..J'. Sucg. SS:L=5-151, 1933. Clin. 27. * The dbst:uction of.cytcp.lesnic basopbildau-ith micaral acids.. Stain 51. * i„e c Tach.: 2E:9-12y.1953. venou 1955. 52,. ~Cvari * Lr.dicatao senior or sole author. 53 . Ef~fec56':54 *L9diCatef
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233 Bioiiography - I'ali+inR.Flsner„ ::.D'. 28. * T1ie p:.tholczyof a p^eunotrcpic vi ruslntcat in 0-3-'.i aice carr-7i'ng the Ei::n^_r nilkfactor.. Arch.?ath. 55:1G-1'9„ 1953.. 29... A r.aturaiilyoccurri:c tc:or oP cray'squi.-rels ralated to the Shcpe rabbio fib-caa. Proc. Snc. Lsn..°.io. L6?:203-301, 1953. 70. ' Cbsarvc.cio-scn thvr.oiu cclloid.P.rch Pacli~ :G:2i3-235,.1933.3L. Y.etaeiinonaticbasc~'.ii'-iaa ofI:eratinafter o;ciJa*_ion clasva-,e of disulfidebonds. J. 8istochaa. G CStoccea. 2:95-1D2', 1454. 32.*Raturea d staining razationsofthePibro.nac^_11 izciasio:as o: che Shopaiibrcraof r:a`-S'itts.. Ji. H.at'1. C-ceriaatitutc 14:335-365, 1353.. 33. Further eoservacions on tha:role of bile ia.ta_ patho,eaesis of p,aa.reaGitls. 9urr. Forcn„ Vol. 4:4GGi-412, 1953... 3'+.. i: e pat;ao7,aaesis of farc=a in, cottcncai'1' r..uhits. :,a. .Ii. ky3iene 59: 104-112, 15.54. 35. '' Gl-arular llpoictosisin.dog kidney. An. J. Vet. P.es. 15:225'-2$6., 1954. 36. * T.`ie e-- t of aethy.l'aticn cn b3s.ophilia,'.,J. F!iscoch- & Cytoc^.ec_ 2':81-87; 1954. 37. * Tae patiiolooy, and pathorenesis of sparn.ine induced reul'.disease..l.rch. Path. 57':2w4-254., 155a~. 38L A1kalYce.?hosuhatase ardl;.eri'odic acid=Schifcreactioa in t4e?rosical tubuli_ o_`the' vert_brate'Yidney: A study in segcental d.i:feraatiaacn. Anat. F.es. 120:1-21, 195». 39. \ephrotoxieaction,c:c sperr:ine end related anines. Prnc. SIXInte-iat. Physioli.. Congress. 714-7'13, 11953. . 40. T'ce.effcct of increased hepatic blood fleuuroa liver re3e.r.eration.. Arch. Surg. 69.:'_63r27.2,,1954. 41. * Cytoplasaic liver cell inclusi"6nsfollh•_dnfi arterizli'catden inthe dcg: Their nature., signiiicoace azd relation to other ezp_r'=_a^_a1lyinduced' cytcplas:nic inclusions. ?~n. J. °ath. 30:937-1083', 1954. .:42. *'P.ie occurre: ee of c+,•ooplias-ic 11N~r celiL inc'_`asions iolla•.r.imgacterlolizaoiorg in the doa.Fed. Proc. 1u.:L2o"-429„ 1954.. . 43. Liver re:zenzracion fol:o-'iagcc:.~?iete arterializatio.^" aidd inceesee in hepatie b'-cod!flew... Fed..Proe. 13:44, 1954. 44'. * The d'lfferentiatioa of 6neneed-Ster.^.ter.^ eell end, re=ckarypcyte with special rz.ecance to the periodic acid-Schiff reneticn..L::.b. Iwves. 3:' 26.1-269, 1934. 45. *"rscedbWucinocs"'cy;tedano^a - A nimne^er? OSstb'Gy::. 4:a16-621~„ 1954. 46. * Henarie lesionsoiacuce he-rrcao?'c panc.-eacitis:Tnei'r nature andpati~ooar.esis.. 5--_ .37:213-219, 1355. 47. w The praceScal valuee oi histopacnole3ical classification of gastric earcinecac an appraisal basad'on 1100 consecutive cases.Caecer 8:389-355,. 1955. 48. A l:nipp'_e'sDisease.: Report of case aoparently cured and discussioa of ch_ hls.occenicai features. Clev_01in. f}sart.21:213-221, 1954. 49. * Co=bi;=d Go_orim_tSedsforthe cerens:rao:on e= panereacic a1?ha a-dbetz.cells. A~..Jt CLin. Path. 24:1433-1434, 195'+. 50. * Satiaiactoryslidecar=!ers for Stander andCo?1in contaicers. P~. J. Clin. Fath. 24:1435-1436„ 1954'. 51. h The cytoLcgiedascnstxation.ar.d significances of tumor ce1'_siathe cesan_eric - venouss bload.in patients with colorectal carcinona. S.G. & 0.100c1'02-103,, 1955. 52.. *Ovar'_an.cystoaas: CL'ni--pathelogic ebser.at'-o.a. Cancer 8:437,-445, 1,955. 53.. Effeetso.f re^in in rats treated c.•itti.eethylzndrostenadiol. E.^.do cia. 56:541-z46, 1955. * Indicates senior or saIle audnor. H9 'N i fi 17
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234 Bibliogrcphy- Ed:znR. Fisher,li.D. 54. *Strc:.a L~;:.,_hcr..ctcsa (Ilnshi:c.Dco) in inc nalc. 2,^. J. Scrg. 91:60-65, 191-0. 55. * Scrc-bot'_c tii=crSoc•;cc7en1= uvn~,:ra< Ce;ort c:faocse~rithdi'scussion ofiCn tinctoric: . stcres. ._,. J. C:in. Cath, 25:E20-..- , 1955. 56. The ce~ericy of aorcic a.carioccl'arosis :¢ cc: r.i:c:iseaces: A neeropsysoc:p,. !- J. ::_.,. Sc. 232:335-3~1,. 1935. 57. The steriiiz.aionen: storcge of iyophitb-ed; bio-d vnssals. Ara. S,rg. 143:71--EO, 13i6. 58. = 12or-apinephrin^_ ce11s of the adrenal: ca_uLla foll-:rin; hypot;-e=ia and unilc,:ara1 adre-c'-ectcWyin therat. Prcc.Scc.'v.~ec. 1,io1_6:!ad.69o 140-142,195:. 59. Fu_tSar. e.o^ri:_~:aca'_ observationson ani-el!s witi' artcr_aliLad livers. Sur3. 33:181-195 „ 1755. 60. Renal lesions of sulfcn.u.eide typefol'_oain8 adHinistration ofacecazolrt-.ion (Diar.o::). Ji.k.ILA. 160-204-206,. 1956. 61. * Dariar's disease of the A.>i:A..Oto1a;yng, 62:438-+41., 1955. 62, *`7eurobla.te~as of the nasal fossa. A.M.A. Arch. 2eth.60c435-439, 11955. 63.*ice na^ure of the periductcl scro~a L1 2ynac-ascia. Lab. Inves:. 27.5,1956. 64.ih.e heoatotoxic effect of nitro^en c•,stardfollbwino direct '_ztraportal injections. Ccncer 9:14+-147, 1955. 65. * Histccnenical o'ose n,acicas on an alveolar soft oc:: sa.-coWac.itHreferance tohis.ogzaesis. .IlLJi. Path. 32:721. 1956. 66. Faca of au_o~~:ous s<in, t~be-- as aortic gra`_t-. S.G. & 0 102:309-315, 1056. 67. Es?erihestai reeaastruecion of the aortic bifcncation. SarB, 39:940+949„ 1956. 1 68, The effect ofinduced arCCriosclarosison freshiric7ohilized!.-.crtic horograftsin tcerabS:t. Serg. 40:523-532, 1950. bh. Maligaant blue nav-u-s. A.U.A. ArcF.Dar.aatol. 74:227-2-21, 1956. 70. Sexdifferancesinn'ne sprec3 of eoloreccal andivesicla_ carcincnas. A'nn,. Scr.,. 143:2&4r'_~5, 1955. 71. * Cletfareation in the eer.aonduct anenuscsl ce-..l:cat*_on of prica.-yhzpatic carcinc=. A.M.A. Arch 5urg. 73.:251-255, 1536. 72. The effect of h}?ctherr_ia upon induead baciereaia. fied. Proc. 15c514„ 1956. 73. * The nature of diffuseintra-a-t^_riolar occlusios in patientswithcarcincna. ?`!. J. Pzth. 32:1185-1203, 1956. 74. * Does the zcrtiahenograftd~veiop arte_riosclerosis? An experiaentali study. C1ev.C1iz. Quart. 23:159-160, 1956. 75. * Parathyroid cysts. Cancer 10.57-62,1957. 76. Postnatal char.;eLz the a1laaLinechosohacase actlvityaad the per•:adic eci'_-StF.'ffrecc:ion of the r..ousc kidaey'. Q.Ji. M!c.Sci.97:187,i95y 1956. 77. t E-ctrc°a-:nary Pcget'., d'seosa. P.^e._. J. Scr„ . 94:493- Sd, 1957. 78. 0bserratio.^.sconcer..inSvacuoletionar.d decosition ofglycoEen in nuclei of heoatie c_11's. J. Lcb. Invest. 5:324-333,. 1957. .79. The effe_t of hypothe^.ia upon iaduced baetereaia. Proc. Soc. E:eper. Bib1. & ::edl. 93:510-512,1956. 60. = Polyarteritisnodosaassociaoed vithrheuaacoid crthritis. All. J. C11n. Path. 27:191-205,. 1957. 81. Paaer e1'ectrophoresisof seru.c nethods and applicction, Penn. ):nd.Ji. 60:972=97.5„ 1957.. 82. Soce practi'ca1 applications of histoehenistrj. Penn. 11e3. J. 60:1467-1472, 195 7 . Dibliiogrpahy 83. *ManinE 84. Stress 1957. 05:. ..u1ti~ 32:107 86. Brcnch Are 87. A k:is: aice. (>:Ll' 88. * Trans: 89. * ALcerc Fed . I 90. Paohc: Are`.. 91. H_s:o, % ne2 hr, 92. Pat:^o scler 93. Focce1959. 94. F-ib7:573 95. Epi:'.e 96. * Poss 97. C"Ser Su•,~,, 98. Pro~ 99. * Effec de?:y, 97:4r 1C0., A:-airt 101.Sacc: 17:4 102. * Ef:e- rabb 7:23 103. * EfE: rabb 104. So.ii ti niv 105.. *An~ 16 : 3 106. *Patti 9:12 107. ^C+tc 103( 108L Obse neur * IndEcatei * Indieates senior or solie author.
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;t 235 E blibgraehy - Cd inR'. F.i' ner :I D 83, *Meningzal hm,aaoioper.ccra.., lrch zo1. bPs ck:et.,79:C0 -, 1557'. 84. * Stressor eff.cct of hypo na.--1a in O_rat.c k~. J. Phys_oi. 13. 470-41^_', 1957. I 85. ~T :(ulti?1e endocrinoo tumorsar.d peptic uloer. Ga:,crceaterolc0y321073-1Gr4105785.. Brcnehaolz e p rs Ta.(so-ecllednusculer cirrFo:,isof the lcn3s):.. A..~ J. Parn33:113 '1b2, 1557. 0 105. * Ana~naPous reduplicacian of tneeircl~e of Idillis. J. Seuro-suro. [im . 0T. AA h.istocne^.ical bas.srcr cncr.qas in . rena1 t¢~ular zu-:c:ron iaycun; c.ice.P-=rait ces. Coaotesi:a:-4usle .-scciatio:des :,nat=is:es (,,:iL'I)! ecr.ionAr-. 25-33jiu'_'1'a , ^55):. 58. Transitional ceil carciocna of ti:e~urachcl apex. Czncer ..,245-249, 89'. *' Aloerat?on.oi rsnaT sucoinilc d'ehyZrogenasa in.nepiirot.o~uc sa^~a naphrosis. Fed. Pros.. 16:356,, i957'. ,' 90. *°athologicacd hist'ec`ia;ical~ observations ine:cp,erl=eaaln hypccSar_ ia. A'rc:. Snro. 75.:817-i127, ,1957.. uA'_scochemioal cbsecvaribr.sconcer7irg sor.,a renal enzy~es in n^2 hrotoxic nephrosLs in~caerat. A:ch. Patfl. fik:n64-672 „ 1;57- 92... *P.a.ho:cgic obnervacions contzrning che kzdr.ry. in.?rodress;ze systcn:c scl~erosis (~?.S.S.)'... Arch. Path. 65:29-39, 1953.. 93. For.cedhoriconcalconysugaze ga=e in-an. ... Co.~y. Yeurol. 1i1C:257-263!, 1959. 94. Hamiballis.=us.secondar.yta cetastztic carcino=a ofgallblcdder.. :Geurol. 7':573-374, 1957. 95. En'-d^-r~al c;•s^_ ir..boce. Canc^:r 11:643-645, 1953. 95, *' Post infl~natorytuaor (: aatho^.a). of 1un-,.. Dis. ofC".2st 36:4'.-43'y 1i?59.. 97. Cbserva aocs ceccer~in^ bact'eria'_ defense aec:^.enisrs duringh;;pocnerr..?a.. SurF:. 4:3.:C07-314,.i953. . 95. Frc;ressive dystrop7iic e: tornali opt4alr.o?legis fo1lowing, tzauaa. P..M..1. Arch. Cc:ht'aal . 6U :422-426 ,. 1953. .99..* Effect ofr.epfiresi's onn renal c,0.2~ and' h'-'stec^.e.^..ica1 apoeaeance o?snccLtic dei:ydrogEn;.sesa:d cyrochroceoxidase.°roe. Soc. Experr. Bio1....6L'zd. 97:44'0-4j2, 1933'. 1C0. *P-~inonucleosiLa rcpnrosis in rats. A.:Isa. Arch. Pa[h. 65:545-553, 1958. 1011, Successicl si:in homograits in pyr'-doxin_-deficient rats. Fed. Prod. 17:469, 1958. 102. * E.`:ec0 of re1a1'l:yTerteasicn..on choiesterol atharosclerosi~s in.n the rabbio I. Hisr.opathologi:c and biociemical studies. Lab: invest. 7.:231-247,1958. 103. * E fact of reaai ny2artension on ci:olestsrol ac::erosclerosis ih the rabbit. IIi. ClactropSoretic studies. Lab. Ir.ves:. 7.:515-523.,.'_995. 104. Sodi-n dizc.ecr:zoa:e (hycac_e sodiun)~ in cerebralangiogrep:.yl llnCv. :!icri. )Eedl. iu1i1.. 24:7r'_2., 19M. 16:3311-336, 1959.. 106, * PatSc=,enesis of. oancrsatitis. Am. P.ractitio^er and Digesz ofTreatnenc.' 9t1253-12~55, 1958. 107s *Cytc^egaiiic incLu-sionn disease in the adult. ICesc Eng. J. :{2d. 258: 1036-1040, 1958. 103. .. Obse;vntioas on the treat-ant of b.ai1 abscess bv direct instillaticn of neuer.antYbiocics.. Univ. of ilich.b4ed. Ci11. 24:61-65, 19581 *Indi'cates senior or soiee author. I 0 F 0
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236 }l.Slio~;raphy - Ed.~n I:. FS.s~net, ,I'•D.. 109'. Effact of nyriua;aae dcficiency upons,:i~ p-af[s in~ti.. :ac. Scicnce 1953. 110'" * Ic:c:ai~ticcsicc. c: ::'.:c c-c.o-i•_a1 C-:r.eC in pscudo:ant':-.c;:.a elesticu-:. .. 7. Psz.. . 33:977-99 t, 1;'5i:. 111. * 7ct11clcCief~`_;id?n„s' in .ic..,seof .,.hy::cpi'.tui[_r.i: _,.:c. cicS.etes rcl:ti,.c too h'r.~:nttiyiaT_e, ?-:Lciocr:. .:r,d. "..-_.a..- oT~Pa" inczcrzlcticr:S:ps. d'.::.,,. .._cn. 2a::I. Ji;:232-2^3, 195B 112. t 7eriaaal rhaSa~~yoszrcc:;a. .4'.:i.A. nrch. 1131 * Tt:~.-v~a and _Woz oiacie insu£fiei:ccy. A.tLA. Arct,. Ir.t. ..__. 103'; -'_^'-' 1959. ~ 114. * M:oc±rditis ~ji'th eacu_aulial, elzstocyo:lbrosis.(£-.3). An. Heart 1. 51 6:537r552, 1958. 115, * OSs.r:o,ioss coacc-aag cha ?atNoyc:,esLs of c^docard":aL tnic!:eeing intnc adul: hez a. P,. H~r_rt J. 55:553-561, 1953. , 116" .°.e^al lesio~s of r.i-cnuolacsidar.ea res=s as -ied byeiectron, ierestopv, La` Icves:i^_:icn 21.3:/1-585,1559: 117. * LcEorsto:y and cli:zcal ci_for=_nGiaeicnof' cSrmnic lo-=rclesephrit'_s aad! neohrosclerosis. ?-. J. i._U. Sci'. 235:551-5.5.0„~1958. 118. . `Cs93fy,itg =etas:ati0 c_rCl .,0=3o' i.eJo=t o".a O::~e V. :. rel;,ti"a to Aiscege^=_sis cf ectopic:ossi:Sca abn. C.::cer. 12:=57r2u2', 1959. 119. The ?avorable ef_eet of pyridoanc d.i.czencyon s:vin:-•o:oHrsft . survival'..: Sun~er,~, k4:4n-1ci,. 1958. 120. Zihrc-'votic thrc-Socyto-_aiat pur•ura :; c: .:se af r.,assivegast-o- incestinal Cascroent_roib.^y36:132', 1559.. 121. * Giffenc~:i~ricn of nzop'-astia 1'zsicns c:icra_ce:'_=^d.bylsc~;e,.vacaola_edintraepic=r=a1 (P_getoid)iccl'". .H.A. .4rch..?a.4.,67:1i4'0-146, 1.c.S9. 122. F.eticul= . cell s-rcona of brain ('aicrcglicca). .1.P'~.i_ Aruh. I7euroi~.~ Psycaia:.81:591-595~ , 1959. 123. = E£sper_r..=^tai studi_s:of' 'aetors inflcenc'z0 aeratzc _'_tascasesI. P_ o°_ ncmSer e:tc_?r eells injzcte_ a:.cs tina.oi3ro•.;cn.C:ater.'_2:'2t~-921, in_ 124'. h".;:~_.-i~ental st'_c`_esof f_etcrs '_..°lcznc'_~o be~atic natastasesID. Z_fec.t of parnial.hapatectony. Cancer..12:137-932, 1':S5J~ 128.. Denignn retro;.zr'-to::eaL r.aseaciy-w-,_a(i4aarcc~a)::,rcS. Sucg. 78:975-97ES'y D95' 128..^ .._ =e.•:-b.-anous. 2;ld proliferativa glcceculocepStitis of}ie?atie eirr^csis. :,n. .1. C1in.Fath.: 32':4i.-55, 1959. 12T.* His[cpiasoosisas a ccuseofsoli'tcryp•_lncnc.rygrzaulo-cs ih Pennsylvznfn. Penn...ll. J. 62:197-i00, 1959'. 123. Papi'~11ary a2.enosa of.--pu11a ofV,cter. A.~..,,. Arch. Su_o 73:..03-1156, 1959., 129.. 6.:peii:..antalstudies off'actors ii::luencii.- .%_ ___ atastnscs ?IL.Effact of, sur;ical trauca vich.spacial refer--ace co injury. A.^i" Surg.. 150`.731-7+4, 1999.. 130.. 9histoe;:e=zcal evaluaCicn of hetesoropi.c oss-ficetio.. a:d dystropai:c calcification Snn the er.;)eriaant'alilySaiarcced rat 65i=ccy. A.)LA. Arch..Panh. 69:32-92„ 1960. 131. *Iavestiaacios of rejr:ction of canina, rencl.ticcotr=spliaats byy thefluorescent.:ntibody,technic. Pr~oc. Sac... Exper. B?o1. & lied. 101: 259-261, 1959. BiSiioor.;a 132'. 133. r-~t P: hca. 134. } ('ab r:a 13:. Es,, 130 136. i;at F.-d 137. ~Fur C.1~ 1138. * Vne, o7a 1i'.9.. A D1'u. 1140. 3._1 39: 141. Ecs 142. * _.._ 143. nes Car E3: 14'4'.. * c:.:o 145. * Ef: ~ of 146.. iae 147. . 'TP~t. A. 143. * De; A' 149. Acr tre 150. Ef: gra 151. *' E? f r.e: 152. Sur of 153. Chr 154. * Car cOr h.i 155. F1c 72:: * Indicates senior or sole author.. * IcdYecte. 39-121 O''
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132.. *°._ct of- cor_isona , nd aoienal!ectu-y on Eeoatic r..,;tastesesfoilc•,:ii; t:ca int•-_':o: c-!~ injca.. c.`. i..ah.cr 255 carci-oscrcc: a. 9GCh.,75cc9::-699, 1G•~9. 133.A .'ll'C:J!'uC'1!_31 c'1=1,C' ^a of h::v'i0.'_CP:^ '._ ess_fiC:.t--C> ..d dy,s_:opt1:-zz Ca:C____:a~cn i--v i:1fCrC?_J1of C:.2 r::t [._Cne.'r (cos :ac:) .'~. J. P.a:h. 3..701-?03, 193?. . 1;+. a=fcct o: -aps:n.. J. .. ~tuoi:an.: G C;:'oc'.'em. 2:102-104, 1;60. 135. E_ip•=e_=-rcni~•:iE=ae: ic sepport of, lth^dor-ssts tu:ao: ec11i.: Sciec e_, 13J.:9=;-?1", 1939. 130. . =..:. _a='ien of s_-.i^ic danycrog_nase cnd cyt.ochrc:-e ox!das..e i.n rat k-Ca_y. .._oc. 9oc -:?er.. Z_c:. L,.d. 10i:731~; 1-D137,.. aFu:zb.=_c ~. ho'_ogic ooserr•acions on cne svcdre_s of p!cpti_ u1ce: asd eu1C'_':.j1eendocTine ca=.ors.: Gas.c.._.. enelog;• 33:7.53-4'5c.156C.- 135. * The a;sociaa:n oiScio^~::hic h'_:-ochrC^._=osisG9d e±:cessive iran o^.er'_osd`. P,e:ort of a ensu vit:i~ cc-=enc to t`re concevt cie_:o,z::r-s ~er.oc'~ro_atosis. A':cn. pa:h. 68:'33~fi3:8, 19=0. 139. * 7SGC~~i; accd at'ec_..._te,a e~ocli. 6,. JS ..ed. 29:17a-io"•J, 1960', 140. Bilacnral! i.wasiv=_^primarycarciaoca.of lucgs.. Dis.. of. Chesc. 59:421-42!~, 1561. 14'1.Eosia_p:^ilic pe:itoaitis. Ann. Int. 2(?d. 51:301-309, L959. 142. ^_..a. o_ciccic acLd-Sc:i`.f-: tiez as as aidin.the dif.ferenoiacicaof vasoc;;e1_cca. Cancer. 13•:i:)7-o41, 1950'. 143. Care-.c-eoF prestate in~:i:e ausence oti'tas:iculartissez.. J. L'ro1o;?.y. 83:+03-4'70, 1S'60. 144. T-::oer__e:a a s.edzes.oifact:o~s in:lucccizg se^atic r..atzstases. IV.. E::i: t of CirraL34S'. G:-.^.c.-r. 1i.n0-(:64:, 1960. 1+5.. *~<c^^..._•.cr1 s...di'^_so:s_=or.sinflu.nci:Ghepatic r,.ztascases. V'• E:=eat~ of ccctis:caaand a!relcleccesy: Caneer Rsse-r.cS. Z0:L'92-496, 1560. 140. xT:1e __c...._ ofhy2l=rcension cn, ci-.ol~zste:cl a_har._sc'^ros'_sin.c._:aSecic :aJoa-_ ia*.... I::vastigati:cn. 19:3b1-372, 1.61. 147. 'ti ?hthcl':;;yo.`-___o;leral vascnlc!- diseases. In ^acyclo?edca of Card:olco.y. A,. Lci..nC~ap. 10, b4°41959', ;cGr~s+- ;11, 17i3. * D=:g -~r:ati.~averrucal endoeard:bsis. In B:c7cic,nd:a o: Cacdiolooy.... A. L~iise9~ Ldi_c C.hap.. 33:, 1i70-172, 1950~, ..... 149,. AorticG')2•ofno-ai, c'nolasCe::cl.-fed, hypertensivaar.d certise:,e- tr^_acedrabb'_ts. Fed!. proe. 19:1.4',.1950.. 150.. ..::ect o_' h;•arocor:isone, escradioland.nast eell!de?leticaon c-rra,geenia: grar,:! omay Fed.. Proe. 19!:1+w„ 19E0. 151. * E=fect of e._re-:;i?cco~y co:tisoneacd hypopcqsecto=ycz a,itoaccleoside nea::ro-,is ia.r.ets. Fed..2roc.. 19!:229. 195.1. 152. SurSicall i-~!ac.cat!cs of tio3gY.in's di=ease of' tiiestccaeh..to thesan ofaSdee.ir.al ::ali'~. Ps:Z. Scrg i50:IC0~-i005, 1959. 153. Chr:::.icr.=iienucleo>idz ?rocainuria. iaS. InvastiC:atian. 10:C44-4:0,. 1961. 1154. * C2rra,g^enia granuloma in the guinea pi;, and rat'. 1. hyd!'o- cortzscne, escrcc'_o'-!zad casc cell Lzplerion on '_ s tiiscolr'_cal aadhistoeh°~ical .¢a:nr^s. ek.:{•A'..tr^h..Patn.. 70:55`-575, 1'96'0. 155. Florid ^^pillc.ztosis of oral nucosa and'lar~:x_ ~.4.i:.A. Arch. Ocolia:ynh.,. 72:593-553,.1960.
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238 EfS1:cg,a?;:y - F.d'.:"n R. Fisl:ar, >I.71 EiSlio~rnpcy, 156.' Df..ct o:'r-.rcin cnn c!ioloscerol. ..::heros::~.or~a i'ut thc raS~'i:b i+:oc. 180. ~l'lr-cs Soc.. G:7cr.. ifio:. t1:c c .. 157.. *El'it'..a- in suopor: of cha neopLzsc'_c ett,ru efca:dicc ny: ona. A"a. 1lelrt Ji. 6'0:U:i:1+u.D.,, 1':60. 181. *.C,-c.. r:-. , 158.. * Ti:e Tissue : as:: Ce:i. J.A'.:..r.. 173:17d-173, 19u0L 182. L, 159..i0 EPfeci ci: rcoal }q'puro=r.sion cn cholestero'_ a--eroscle:osis i¢.corcic:e-e- 8;.:31. Cra~.edl ,1h. J. Pat... 160. * Lff:ect of: , chnizscerol _;F.^:ose'_!crosfs, -;.n~_^c.-sic^ ,...- ...,_;_seae na1 103.. ;:"_ P aort?c n!-,~:-n consn_poica in „hc rab.'ci.c. ^ 184. . ` S; :720-8_[0, " 19001 .. In : 1I< 161. F_<peri=entalstudiesof factons ihfltencingho;'atic catascases. VI, LrV.^.: L r.ccc o8 nutridan..0arcer. 14::..47-555,. _.__.. 162. Pa.:'r.ulop_c cbser:aticnson t?ia cu:cneo" 1-.oaofpro;ressi::zs;~sco-ic 1~5. - <ffcc' P.r.:. 7 sole.rosis: ,.-, electr-aicroscc: ic, hi=[cc i'ct.ical ar.a 18;i. +' ;i:+d??- soudy. Arthritis 3:~36-545y 1,960. sco~"' 163. *' Effect of e:dr_nalectar.y, corcao-a ar.d i:yecn:-ysecte_y-on. ~inoncclecsida 187. ` Diff.rc neph:os!s. A.II.:,. i.ath, 71I:12S-13o',1'.b1'... gic: d 164. Observ.at'-ons concerning the si.g,ra',zcaace cf f:Srous andf_tty tiss-ja ic 138. . _ n^edle 'oiocsies ofthef li-r. Sz_. 2 39':~-4D2, 1560: Effac 165. * So-ca1~1Ld'Collagzn,Disaasxs. In 3:cod r~nd L,-,-,ni+ Vessels. D.I. A::.=scn., Hioi. Ed'itor..Aea'_ec:ic P.raas,.Inc , ;LY. 6GC-,7U „ 1;.J_ 166. w Eari:y, of'hepatie c atasresesin,cirr::osis - Ani .. scoaceptic. 1i59. ^ Er.pxrof ro 1L7G:366:-370~ 1960 ` 190. *::rc_. . . 167. 1T.eeffect of alteratieaof liver blood f1^w uac n e~:~_N_=z~ta1'.he~ztic ~ Arch. cecascases. S.C. L0..11"2::1i1-15~, 15u1. 1911. .. Nost 168. * Effect of ::,at ceil depletion oa.~:ound:heaiie.;, 36:139-191 1561 S..Ir.ceat. D=_rxa:oli.. 192 Ik-eri c * Gra: , . 1169. . *:;:estructure off the respiaato./eni't in cor.c.ec a~d uncc--ca~ . . ch-i types. ..~"':. Rev. Diseases. 51:733,1'i~0.. (Cr~n 1170. * Renal lesicns associatzdclch ranin protaL^cria ~ revealeu.hye L c[ron~ 193. Sc:e nicrosco?y. A.N.A. P;_'ch„ Pa:n,.71:4o0-4Z4, 1:01. o' [c 101. * cff^-cE of:eticuloen.lochei.iaL inte:ferer:ce ca~esoerin_nca'_ 19,-. Arte Sur3icali . Foru= :{i., 57-59, 1560. . stud 1172. 0 E:cpericoncal1 sCccies of ..cnors...Flicanciag ::ecatic n__as...ses. V:: 195~ '~ Gltr¢ E: ect of te,iculoeecothzlial ii:car2ar.cee. Ca.._zr ..3saarc:^.. 2.1::z75-3--.i:... pro:^ 173.. Ohs-r-rionseor.ce-n i^ sple.en henoe.r.aasplcnca:io~ cormal a.a ir_a:aa._.e 195. Libor anitaa'_s. S.6. 60.. 12:2.:655-G62'„ 1961. 197. *1?ole 174..' i,l~ectrcz microscopic, histoc:.enicai and Histalcgic :eaturzs off t.._ 75:51 t`alker carcizoaa. Cancer ::esearc'i' 21:52T-:31, 1'9E1. 175 ~[Uoleof :+cculacansa in ranan :ornat'ion. Pcc. Proc..20.c:1 „ 19v1.. 198. effe: 17.G..* Correlarien of jus~~g].cnecuian ~_r.nulaticn, pressor ae:iv.f:±.end enc-:r.es. rat. of'r,acula dense in experieentaS c_•,pertcnsicn. Lab. Ir::ostc~atica. 1C:707- 199. . * t.'h;'nc 71:8 1961 21O Fibzc , . .. 177. Carciaoaa in situ a;ising in.squanous m~etaplasis oi~ paacroaticd:::cts. A h 82' 674 5 673' 195' .. 201 aea. Cral rc ... urg. - : , _. 17.8. * Cogan'ss,vndror.eand sfstcaicvascular disease:'Ana;ysisof paoholc¢ic . ra cr< featuresvith refereeee co its r?1'eticnstip:a t3rcrfroanoiais oS>:i.eracs 202. ` Gaud (Duerger). A.:1.J.. Arch, ?ath. 72:5i2-5.92„ scop,: 179. - oer•~..earaL studies offactors: _nfluenci:^ opatic -~.....ast:ases. V.LiI. - Effect of aa:icoaCuin::cs, Suroer,.. SC'cZ-C-24i, 1°5'c *Indicates : *Indicates senior or sole aui.io:.
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239 ;i31i.;;::.;.t:y - [d,i, r.. rist:cr, 180. -`PLtres:tructurc ofcoPcaic vitiu c;eci~l rrfzrcr.c~ totlie e:'ilii:e11a1'inc'_u5:ir.,oi (::.::.cer 15:i60-17.0, 1?c_'. Curac,, t::_ar)) of tl~eu.inaryJSlcLder in d:c Ji. Ubo1'... 1"u3. £.>:~t-i-_ntel s¢utiies of factorsir.fluu~ci::^li~:ctier_,..atascs.. „• 'Z,.,; v 15Gi. :.^.n., Sur; 15+:3+7-3:!', : 184. ••'5,^_....!c .^d'.1'ncai £oc.ors _..;1u.:.uei:;;',dav_Loane== c.i.^_oaCic r_cWC:ases. In:, Lc. i•ord IPCSt I:::=r:.e1Lticnsii:ps. L 'L:J:~:, Go., . .4:3-.62.',2' n 135. =ificc_ of hy;.erteosie os.cc,cular m:dio.t:er lca-bnsof sertr. sici:eess.. J: Pat`.icic;,y. 185. *?f.~ih~Le's d sca<>_: ?•;,_;~~o~r.ecic cansic:era::ionsS--d on electron nicro- scopic sad 196?. 187. •Di£;ereatial ci'L_aosis o*apiller.~, care=:•.'.ras.af c'n;.:raidand s. + .!'v;,ry g..iwcd ori';i:a. h.^. J. C1?a. rath. 37':'vJ:-633, , .76?' 1"06. s.ud''.es of c:.oto.sinauer.o:.ga~a~!c -.cLstases.._. E:ffaeu c:hepetic tta_-a in nypo?iysec[cc-!zcarats. Prec...Sbc.. roer• Hl.iol. G ?Ied'. 11-3:52-u.4',. 1:%4:. 18.9, xEn?er:-catal stu_~-_es of .-cters i.^.~'~licsn,[z,>,:':^pa[ic r_ zstzses. of r_.c.iculoendne:^ollt1l st:c.uU_t+onc C-.ccer 5:. ._ _,..__ 1.9:p. *. P.r^'_uc^_on of hapacic La.a:.,° Cyrac.icuicuaco~_iieliui interiere. nce.. kr.c7r. :'sch. 75:1:91-195 ,. 14&3. ., 191'.. ti6s: fzctors of r=c_stcsas. Surg. C1in~i.. 192. * Cr.a:~ular-c~11 :.y^61z_ao-~- l..niss.or..ac... :1^ctr,~r..Yiccos.coa~a s..d i:isno- che-i_e1 ev.ic_nceccaccrni:; its Sci::a.^.nc_'.~~: detiia-:.icn e:.d'~na-ure (G:cuuiar-cc11 So.`:::au:cc~ a).~ Ca^.ccr. 1'5:9:5-95:', 1932. _ 19:3... ' Son.er fnrt:^.sr eer_iaza_ cor.ai•=c:atic ~si_^crcicr,: t..cco-.?nra[_ve toz'aic-~ nf. cc:zz:ast .,.__eihls forr t.i.~ do?kic; e;. ' 1S >. Arterioi•enaus fist•aas scd 'o<:ctcriai e ndocarcitis. Ar: _~pari :=cta1study. Svtr;ery. 52:.5:3-357', 1952'. 195 ~t Uit.~st:cc:•o,zl ciia,:-gss of .... ..•:dnay ef:er _efucion of :^.o~.olc~ocs PiOt-ir5. Fed. P.r.o.:ecCi:'~s. 31:470., 1:'~?. 195:. L.v^_c reF,aaaration ahna... Sur:C=_r}5'_:.. '-1G2. 105., 197. *' Fo1° of. Sd^.v.^nn.. ce}'.ts -in Vaileri~aacag-r.cra.ioa. ....i.a. .1:ch,. 75c51!7-527, 1553. 193. of croo=ir.ncia. Pu?eticral azC'u!rrasc-v^^c-a% cor-_~'at'_cz.efeEfeccs _ in;i:>io:: of hc:-ole~qusaad ire[arolooocs proccin (35A) in t.._ rat. La}i_ icvest. 11:oi7,-b37; 19.i2'. 199. dis~ase. Ecitor`_n_. J.~... . 131:.34-e35, 1902. 2CGL 2iS_ocalo+_f: co_f:c due:onatcplas:a :zpsu!~tun. ..e•a -,-,F. ... Fizd. 207:593-5::5; 1962. 201. Gral florid p=_pillccztoai- Clinical, nath'o:o7,iss1 x=.cd d aic=osco?ic ooser:atior.s. A.rch. L'ercatoL. 202. . ~ Gaudtzr.'sd:seasa: Paeho-,ere[ic consir'aratic.ns cr.sed oa electrorv.ri'cro- scopi~c rnd his:oohemical o'oser~.^ations. ..`Z. ?. Pr.i:. 41:6'79-592'., 1952. . . *Indicatesscnior n: sole autNor.
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240 8ibliiogra~h7- L'dais R. FisS'er, tI.D. II!blioqrapny - 203.. E_:perir::^ntal f`_c,Crs; in[luerc!r.c hep,cCc e^_.as*_zses., XTL. Efcect of 225, • .ep irot, iacrz::;,- ar;ar:cli olccd f1o<: Proc. Soc. Lzpcr. 3'-0l. 6 tfed. 1`2:. 1?6-1_; ii53 , h 20'a , . x Pa h J h f d ~ '' 227. T':_•c_pl .. t o .o;y o :^.;:s an t i's.rei .:tio;.sh n to hina^.disease. In: The h 223, An evai! Th•r us in T.r~-.unoSiblcry -c . 1;:A. Good. 1 oe'ocr L ilh-cr. Ciuapt. 36,. 1964. n., f ren- 205. GCa.nt c•-11 ccrcd: oe„ afl 1cn0. Canccr 1i5.: 10-30-?0:0",. 1953. 229 . . 1lce.r Ca 206.. *' U? tresrrc:etural oS;.rvacicnss cencern'-ngtl:e effect o`.. auer.icee on :_n.iia- . . Fo:us~ 1 e nncl-~eani~.e r.eAnosis wich reierc:.ceoo chaz.echar.isn.uf prnteiccria. 2-:0. For:iicr. L;.b. I:-esc..12: G59-5'_1., 1Su3. a^ ci•;it 207... ?Baal! ...~otra-s?'c~.tation inr.r.d thee effe_ct n, p;y,ridorir.e 23i _ 1 *'? $ d+icieaey Sar_ery :- 79C-79J 1963 . a.o o .. . , . .232. P.ro'-ot: r,. 203.. UStrcst:^::ctura! stndyofy sdenir.e iahibiltion.of an.cor.ueieos:de nephrosis.. , .stula f~' Fed. 7roc. 22:.2-,7,,.19"u3. 2::i3 - ro' d * Tti 209. *Lfi~ect of renal hvper:ension in sec':u deficient rats oa.jc_otnElo~_r::1zr .. - y A~1. J . ir.carand zona g.o,-;u,losa. 2roc-Soe.Espzr. Eiol. L:'ed. 113: 37-39', 1^>63 234'. P.at.`.olc. 2).0. . ^=>:;ari^.cnt1alL factors iaflualcin" liepao''c netas.:eses. ):LTi. Effect of 35 nhlcrs- _an- Si•: hepa;ic r.animulatior.and partizl he?atsctoayin parabiotic pairs. .. y of i : Car.cer Rex. 23:"065-900, 1953, . 23i . ...,.. * 211. Investi,aGions ccac-_rang thee role of a hc.:.orali '_actor ?n liver . . ta reg^_necstiaa. Cc!;cer Ses. 23: 914'-920'y 15?i3. • nec-s C - ' d 212. *Uitr,s:ructcral hep=tiacc:-3es fo1lo::ir.;, partial ImDatceto~yy and 237. 23E ero : . - Acc_SLA poroa.cavat shuat.in thenac... Lcb.. ?nve.st...12: 1963. . l l 213. ^ E::~zric_atal stcdics of factor.sinil_3:,cic;hepatic r..ztastas-. kIV,.. 239 ct_ra Dios•ri'i Effect of.nrolactin. Car.cer 7es. 23:,1532-153?„ 1963. . l 2214. ~?ct_-uc:ear f.zctor insensi'cizcd 1i-.rti.and.serum ?roc slti~-hcaog-afted 240 cr.:J '1 *' nole cc dogs. Proc. Soc, [Yie1. 6..7:ed... 113: 872-876', 1933. . 215. Lnea1 £z._^orsc'.fe.cci'n0 tu=ar ;,ro--th. 1. Efiect o6 tis sue hcrsobeaaces. 241. Re: -1 c ; l1 T Ccntec 7as. 23.:..1951-1557, 11yG3'. 21 2 rzn p . ~• 216. Ti!:sue trcnscl'ancat':ca aad zaa reciculccndatlieliel s•;stc -. I... Eff.ect of , . . z . F t4 i slcian f;- -_., in rtocaali aai::als. T..aaspiantacica 2:22°-23 4 195 4'.. 243 . a l f 7 % .217'. Iissue trens=l:ar.tccion end retic-uloendoa.`.eliai sy>tc:o. II. E ffect' o: . .a;.o - . - f vita_in _5Lafic!ency i:r.pra:uLoyec_ic ac.:i1•ity in sScin Eraf~te d ar.d zo. - o G !'e< ' ncn-or._fted.an:~sls. Tran~pl'ano_t:_on 2: 235-24.0,.196A. : .. * Ll tt 244 218. Ultras.rcctura of r.pnin0.,r_as ~aith cc.-en.s r_Lative:o the de ri•:atzon . tr..s th t end; n__urz of the'-r cellular cor:ponen*_s. Caacer 17: 233-241, 1954. o e 245 3. l 219. ':zyali.^.^_ droplets of renal tubular and glozanslarr epi:he'-iun: Ocsar~.a:'.or.s . o c;? `er, C co: ac::.i:.^.-, tae.:r nature a nd derivatica. J. L;2er... 6:IOlecaiar. Path. on ~~ 3:304-319. 1964. Qholes> 220. , PhysaLi_°:,rous variano of carciaoca.of eoLon._ Czr.cer 17: 259,-253.,.1504. 46:577- 221. The 'oiolo^; of'. r.etastases. ?a:Cerrenc Conce?ts im Scrgery. P.c.. Jo':a 247. 1. s,ac:< L C. ;n 1?. Davis... 2,eGra--Iiii1 Co. C;n;.pt. 8, 321-351i„ 1965.. ~ 222. ~cost.iafluence on t:=:o: ,r,ros.th tnddiiszce_ination. Ir.~iolho+cal 9ase.s ~P.e~a1 ~ 24&. E S ofRa.'.!a.ioaTrarapy. F.&. E. Schwartz. C::apt. I.:. J. ~.. i?p.zacc_p : oc. * Co.,,..pp. 4E4-5.1T,.1:66. Lac, o: 249. 223. Effect off experi'centcl oerfusd~on upon thebialo;.`c a:d'~pacSolcg!c lla&. 1. Li 250 iS bcSavior of. :unor. Sa:rde^r' 5'S: 6e_-,562., lc5q.. o u:.,~ . 24' 'A34 224'.. * if.`ect o: sadi- onjuxta~lo,-.erulari¢d_xn cnd cena g1e::e.n:losa?.a : e.~per~.aatal nephro~is. Croc. So¢. Expar. 3:c1. & IdzdL 1'_'.:54':--,4'4,.1963... L^ di 225. * F;zet is.tce r'talig^~at poce~cia'_ ofcoloc'_o po._7ns? For-, L'odec: . cates. 2:edicine. 31 :1+8~-130., 1i363'. =Iadieates.senior or s.ol'eauoiror.
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241 G!b1r oSr. p'ny~ - Ec-.aln. ,.. 1.D. 226. s're~~ nenFc.i'.rt^in t!iyn¢c[c :i;:ea rnU. Pre-r.. Soc. Ezr^_*... liiol'.: F .:`_d.. 115: i3c-1o 'i54. °27. Sc~ ~ n:.pHroti'.c :ndre:-eJn ^-.... D; _oe-as L2:45S, 'S6J, 223: Anevulno.oionc_ :k:a ii'r,,•r - as„•a frc:i .n~tir..nt5 ,._:h ccn=or. Cinccr 229. 4lst_ccnsesin ?-,_ab"oticanio.als fc.llow.inglive_ injun•. Su-;ica1 230. Fnrcn o;,ser.:.cior.s on c ,lor.eru'__r -^11sand ronal ,:resso: ac::vi.tvin .e::^-ria^_nra1 Lca. Inv_~t. 7.3:321-333, ..3L,.* Ro1aof c::Iis in cr.c'7.~it .-:_tioa. ?-rc:'P,r.th. 77:a-3-55.2, .354_ 252. P.`o'un.r,edsurvi•:al o: s'<inhoro^,rn:s in~do„s vi-h t^oracic duct fict'ala. 5•_r;.. -o.cn 14.:142, 17:i3'. . 233. *'TNyro`_c!'a1 ini.lu_nee on~e::r_r-4-.ental choiasaecol atnarosclero!is. Pa. J. Pech. 19d1• - ' 234. Pathalczich'_stoei.e,aicnL end ele.ctron.nicroccnnic r..bso=.ati.ons in EhLar-,-Dziles Scodr.ace. :1rch. Path. 77:613-'_,.,064.. 275. SPryrep-ta*_t:•••ro:''_' h'er.o.crarssplian:ati~os b'v :'aaeu:zr znas'.o.-ns!s -..f.`e.et of i_:a::aoscnnrassi•ic d.ru;s. A.rcn. Su_~ 89:55-C5,. 1:6-. 235..'`•E::~cr!r.=rta1 stuci;., of, faccors iof_lccncin;,. Gevcloo_~acof hooatic ' c£tastases frcn circulntin „ ejeor ce.:ls. Acta C;:tole,3ica 9:1=6-159.1255, 237. Ce.ro-:' -1i::e c,:....ic ...ioc tosis. J~ C1ii... ?atS. 4?:=31-SS3. .~v. 239. % A cc_'air,°c to_-.-.vrpLic^e7iii,^rnaiand sd.axal r_-or in ncvus unius lato.-alis. ll=_:~.c`.o1c^.:cz 130's150-i3k, 156i. 239'. Di-=_oclation ot~:rpn, i~•srcl r.ncer.t : nd r_., r:7, oi f•onalo- tro:ain iit c,r. n.;sis.. Pcoc. S^c. E;~ r B_b1~. S1i6.:1:22- C24, 1'904:. r_r g-o:+th., .1rc:: ?ach. 79:-s5-191, 1353. .. 240. '~ Eola c? -ns' _in - .r.o 241. Re.._. h.c:aotrc~a:lli:, an..atiba. i:1 r.=onncz_'_ c:yr._ctc=isad?cr, ias. Trzn;p~1_ntatizl ..49-53„19G5.. 242. `L'^tic.and elec'ron c±crcccop,ic stcdies.c€ rhincscie:orz. Arch. Path. 7°:50'_-5'13, 1'364. ' 243.. *°.- ct.o8 aldbsteronc nn ji:::^aglrnernlar inuexar.d zona.olo^ecuIesa of nc =ooe->ive.end h.pp,ertaa i•re. rats. Proe. Soc. Expar• Bio1, & ":ed .. 11E : ~''J1-4U5 , 1>b5. 244. * D1tr~a.tr3cnural rcnzlchcc^es in r_ulti-aie noyelo-a v±c:S eo.cs-sr.ts ri.lative~ to the ^•edi3:aisa of pmCeiauria. Lc6. Invast. 13`.'15iL-1Lj74, 11964. 245. Bibic-,ica1 aspetcaof'canc_r cell spraa3. ?roc. :[at1 Cancer Co:.f'crence. Co., PhiS1delpSir. iNi-122, 1963. 2:6. * CF.olesocrol ach~=csolerosis. in rau~-its ui~h czir^.o3.is. .L- J. Pati. 46:51,7-525,. 1:'65. . . 247... .L sy-.cadldridS tec:-ic forrzotd ruscle bio;~sy,inautpstier.ts. J. Lab. & C1i,.. Xcd. 65,523-525~, L965. 243, *'= P.ena1 renin is ualaterally~zpl•,r^_ctcnfa=d hy?,=rteesive rats. Proe.. Soc. Excar. Siol. L21ed1, 1.1iS:119.1-119„ 1S~6:i. 249. * Lackoi th7.--ic ci:ect onvacnd haal'ic,_ Proc. Soc..Expe,-,..?.io1i. & tlad. 119.:61-63,1S'S5. 250. ~+Sodiu~.r aad renal rczin in racs idah.re.^.::i hy,certensiba. Fcd!. P^oc. 24:434, 1955. ~ - Iad3cates senior or sole aunhor. 0 ,~
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242 tiblib; r'_''y - p3u;i1: 2'. Fintier, :1.D: 251. (caliCnant c8enc:.:atoe;t t:.r.or. r.zsonep~lac., so- dr=ral c:.cico-:a o_ J. Uro_ . 1d.a. 252. Reic of in .:u ..nd'trr,o: [rc^sploac;:ciun. in ca~. ra:.. Lah.. I:1ti~ 1t1e111tiJT555„ 1'253.::ri::aacai of. r..:Cast-ces, t:::_°uct oE. 254. 255.. L'.7 tr::c:r.ucn.*eof ac_c_1r.-.d -ec, ii sri'^ ,-,res¢-..u: ~-~ic:r ccc-er„s rz:c,ive to p:c'.:ccia, zL:ects of hcy--.c::cl ra,uit.. An~ : J. Clia. . ~,h. I:(;:1.1"._ LJ!~ ~, 5. 256. of .act.o.s . pnr. 'c IiF.=olc ~.__'.. -.,s. Ca..cer ~ 5 . 2G:ia"s-1S-, 1.">.i5• 257.... i+ola oc .. inrcuii:.-irdne2dl iicCertcr.sicz. L='o. i:rv.as:io~tion. 1:.a~9-G54; - ... 258.. Co..?aris.on o~~~p •:•~loZ_c ef_`r_.cts c5 inp.ri"ilieral ;.,,_ pu;nonary. _.:eriess of thzra:_Sic. =;reh. Pct:z. 0~:5F:-vZ9,1,55. 259... ~-,•luatioa of :. cices o? ju>aa,^,'_c-'rulcr celIsa d Zoaa gLc_.ar•__osa in !w.an e-r=l-o3i.s:. J. LzS.: [ Cli._..::a?. 67:193-- 2C3,. 1?5'E.. 250.: ~Hf.fecto.° sodi;:.n stateoa rcactivity7 of re.n.al.ju:;ta~loncn:iar ce1ls. a._ cdre:,al zo. z glo:ezuio_a. Pmc. Soe. E%.•:=r. :;iu1. & .:Cdl. 1211: 142-1 1,' c. 261. Shc of i.omatoo_nous and 1}-;.:;aczc tc-or. cell d.>. 'c~ir .rib^. _ ,~=:ire-.^al ., S. L U1?:? t ,m. lreba 262~.. -raot s_. c secse, C3nCer i9.:1.,iS-1t9'i 263. .. rat -..c _.,d ;.nc-a!ocs decclcp=_;~C of 3_p: - -L ,- . ve.saaasa cuuse o: nsecdbeardic-ege1y, pu:er. ... C1ic:c,.PLOh. 4b:: 1966. 25:4'. ~li11.-ascrcc-cr_i cosercc*_:n-s o: rssc'z in nYooz-cy ..r.y rtea.:::pr.th}- •i.th so=cisl -~ eLarmaceto rusculer ciystropay,. Le.li.Lxves:. 15:77i,-?9; 265. Fol=_ of th.e 1y~inatic _}•stcn~ im tcr.or In: rncee_di:1Gc Iarcr:nt. Con[. o.r Lyc-.:'.1 alyd Lyannacics. C.C. Tl:cr.as Co., C'ap:.15" pn. 324-247„ 1;05.: 256. ' L>:~ci:r..cntal.ct.udies-.`.`aet'ors ie:'lc_ac4ng ~r.elopnznC of ;egn'zc nc_a.._a,,.,,. SL'1r~.. ?.o1c oftayeoid. C-nce L-~. 26: 22,~.-2254, _.;u. 267. . .__ ases. of: Cencer Cciia. • ,. ,odk.'i:: C..: cee .oseaccile cd.. H. IIcsch,.7.cc,_..Lc .r_ss. Vol. 1,CnsF•~9,,.pP. 243-235.,!1567.. 263. Sra: t-in.natibnoc. lirnp,h codts bytuzorceils... Scier.c°.152:, 1397- 13:3, 269. -Ly~csox3l nc.ure of jcxtc.glu.r.erulzr gresule.s..Scicace.152:1752- 1753„ L:6'S. 270: ' llltresc:,utural .,tu:::es in `.*^.ertec.s:icn. I. Coc:pariscn of vsocular ..ad j,-,;c^lac,a?-. aticcs _n.esscnti:l _ndrc-in' 'n;:pc_t_csiwnin.ncn. Lau. Iavcs:. 15: 1GG?-i>33, 1956. r$' BiC11~og; 271. *'F. v C 27 2'. ~ L• i' 273'. T~ 274. S • „ 275. S 276. I c 277. i C 27:8.: A~~.. 1 / ~ 239. ~ 283. = ? 264', 285. ~ 286. * Icdic i^dica[es senior or sole au:hor.
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243 Si6liogrcpnY. - Ed,in C,. Fi.ahec, .I,D.. 271. * .IaUi nsuip o y ad~ o t^r c ct sis a: ho.cc] o: iS~ =u1 r di. st i . . „ ecs. e pl_.aa C_ '~ ie+ prog ssi';c sYst-_e _.._.resis. _aS, _^rest^115: 14.36_:. _„iu. :Y,.. 273. Ttzuna ..d.J~ca1i:aci ozc: euro_ ccll~s. C-.,.c_r21:.23-30.,.1^57,.~~ 274. S.`:cn~:2ots aad diaoetz> rt.__ ::as. Aa..,J. ..... :- .ti.131: 5%0-571 275. ct_rrolcc:in an e a.r c t ._y ~.li Pe:ie -tastaacs. Pzo.e. :~.. Soc.. E_.. "io.l. 6..__. 123. co 1.,.7.,1i_t.:. ~'27,6. rInvesoica[cmi.of die cffoct c= c1d t`.:berr~lza .~r.-.'. C.:6 oa ?er.tal c::olesterol L;ie-_cselerosise:n-s h.yp,crt_asicz ia....._ ra'a~it. J. ht*:zrosclerasi~ 2es. 7: 307-37:1,, .~,7:.~~. . 27.7.. T1:r or~p.n cisaribct'_cn oL.L!ssCa'_:aceC C:Si ?a6alc.d t.:•-•cr ce11s. Car.ce,- :Tes..27: 4'12-42u, 1967. 278. kaiLoa3cliaaCS:.ad tur.oz ceil Lodae~mnt.. Ccacec :es. 27: 421-425, / 1957, " ,~279.:ectrcn.n.ieroscepicsrcdY of de:re.a1 ca2 i1'_aries in dCa'cztcs eellib_e. - LaS.invcst., 15: 1494-2006„ 1;56.. :~- 280.. y i:ost-Tc_or relatioasRics iat^.e de~elo=ent an•_ g:cw^_Sof :nep,;tic cztas:tases:. l.rgo,.:.e CLr.cer IIospi al Special .: orr of I ntcr-:atioaa'_ Chzpt. 1'0 , 1.9-i~o6, 1967. 2?1. S'2._cacc oS.serretic:rs~r=_ictingto ccnccnts o: ra:rstasis. Arch. Pzch.. .. 3=1-72: 19G7. . 2- *' P.el.a..,-s: ioof h)',i =[e:sicato':~.scuiar ch=. cs. I. C~nel :.d' eztra-rar.al .ascularch:...v;es. In: P.eaa1: Pa~-'c, - I._. =d'tCu~G:n, J.., Ycnr 2oo6:.Pu5'_±s:Lrs, C:~ica^p, ChcaZ. ., ,r 372-395„ 282. 4=.f^_crs of Fotasez- dcfic.icocycn e::csr`_-er.tal __nouescular hyper- ^ tension.. LaS.. Invcst..1uc S7.^-5c9, 1_°6v'. 254. -;:pcr.i:..eatal studies o: factersiaf11c2-c•_r., ceoc_:c r_etast:ses. 5ioni;zcaac_of [rcDped tur.or c^_i!:.. Proc..Scc. 124:: °01~339, 11967. 285. x Yfi~ ',hyr-: 11, Lndccri'na P.t:~olor,y.. Ed. I. L L!ilk:ins Co., ChepL. S, ,-. 1.97:223y 7966:. •- 286. Escir.=_tion of zecosal -ucin.as aa aid i.i.tF.^_ dif'f:=reneia_'_'o^.or7 cclceic .. Crohn's di'sease CCDC) ..r.u e'.:re::ic ulce:ztiv.c coei__s .._. J. CLia. :ac'.i. 4~: 259-2ii9.,. 19u7. -'~ 287... a. Correlation of iaicrastructur_ and pr:eseVlaticn of; ca'ir.e kid:eys.. Lab. iinvest. '_7. 97-1'_9, 1So7'. 2CS.. ~Lltras:n~cccr.l .enal chcs-os,ir- jµve^i~le dicbe~_cs,,it'rr s?ecial rof.creaee to art^riniar i'i^oais. J.?..?L. 207: 289.: Stcdies of: :[etascatic:ee5anisr.s e-_o•rin : L..6ei: -7 ~Tccor Cells. h: = The Prolif:eration :~.ds:pread oc'eoni~stic Ce11!s. A collectie,ef pz; ers pre.._..tad at [iia [:.°~c -fi~rct ....:ua1 ., Ca:.c_r Rzseerch, 1967: 555-582, 1968. " Icdi'cates senior or sole author. ¢ E ' ' if11~ ~
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244 DiSliograaay. - zCvSa 4. , >I.D. 2?0: *Cytc;,:r.esa cc:icatofibr::---- aad d_:-ac:o.;as re:raledl'oycluc':oi Clin.. ?:.:5.. !:9': 1t.o . 291. .. Yiy.ro'_d and rar.a:::.=t, en S-ar;ety'62:.1L -lOJS, i567. 292. tiv,c: atro;pny . G_r ~,c:tccava: s5u nt: A' furti:er e::pc-ir~~ta1 eval-tic.n.S.G. G J: 1_J;1u~o/.. 293. Ult:z~ur~.:cturai studies in !:vocrtcnsions LIi. C.:uty'ne?Srooath;. L.ab. ?:cvest. 1~:.543-150, 294'. Rzsoonse ofe'c.cri::_ gUc^.csef rat to ir.~ccz'_'ssea_i- ;,yn~r^.easica, uren:a and alta_at_c:.s oi sodiun~state'....r:S~ Dzrr.~97,:1c°-2v1 295, The ;iarrier actLez of :~lyr_h r.od'e zo-.cr-.cr ce71s ~-d er'}•.throcytes. I'.. ....-°.al acdes. 2i9:, -^,O7r19i:o, 1:67. 296. The' bircic: fi:action of _i•.a 1•n~n coce to z_--or c~? 1s. II. Effect o:: -r_g,, c^d tueor o:o~:th. Ca:zccr 20: 191C-1315„ 1?~7. 297. i Eistol''cgic, histe~:ca~_ee1 andl elactro- e'_crosco~:o'fsaures of the s:-Inn sr.ots o: d.ia-tes An..,. J. C1in.?n=:.S... 5C7-_L4, 1963. . 293. *Exaeri'-•_',ncai stcc;;, of relat;o^::ai~ tiec, :ae•,t~'^y,7e- r.scca~ o ti~.en gro-:th zzdr...__~-_~-_ , Srit.. J. Canc=_. 22': 3.'2-J:5,.'1Sc3:d 299. y' =_ra'±es in :iyrc:teacic:'.. In: ..nd (:en'-:, z...a.s Ia. E::aa. ~en_~~ Pat.`.oi~y, Vol. ?V:. -., Pajuc_, ... a,dl Jas:.i'_a, C.. S. r er, :I'Y. Crl np.. 3i~251, GB'. 300.* E::pa-i~:ea:a1rcaai' veiaz cons:ci~c:ion. Its re1'ct_cr, to re-,:1'le;io-aobser:ed i•t c tients witi ro-,a1va_n.l th-or.Soscsne.d t:ic' 1ep:]rcic sy,d:cr,._. iab. Lr:est.. 18: 0°5-655', LSI53• 30L. M1a cf host czc tc_or calcica in n...cstcee s. C'a:cer 2cs.28: 1753-17i8,, 1563. 302.. *.?SC^_nt:.tica of Ir.: 21g::er.ts. in 2zc-.o''e^,}:. Ed. brol'=a::. .. ,. Ac;dccic Press, H.Y., Cha_t. 1ba"oE-5CS', 1=~59. 303.Ef:zot of lo-: r.n'_ec.:lar 1-zi,;nt ccr.t:an onhz7atic ~_tzc:ases in r'ahbic. Cancer 8es. 23:15Cu-15c9', 1;53'. 304. The d4,-seaznc:i~n oi •~Lccca:ccvs:y. _:.osulated~ee.11 sus„a~sions. Arch. Sare. 98:2+7-3°11?59.. 305. * Ci'arSotic (i~e^at:c) lobular glonarulcneph,r.itia: Corrcla.icn~of •j'-tra- st:ucturl o.^d elinicali =_st'::res. Ay. J. 57.:' o59_OSO, 1953.. 3Cti. * Repair by regeaerntio~: ?atho'-o.gic, el^ct:C' a.n~ ' pr7si'o1o71'c _v_.._es, In:. ..et`^1o3y. ,.n.nu__, 1Sc91, =_d. S.C. Sc:.__-rs, AnpLcton-Cent.u:y-lao.f.ts..:7'.Y..., 1969. 307. * Tne co-callad co1lc+;en dise;.ses-:d elrst'o_zs of sliin. Ia: of ..in .achollcgy ar.d ?at::opnisioloty. flaluij, E.G., Ed...'.<il*1-`'cn.s & Bilkins Co. 30o'L * Se-cconin,_nfus•_on in raos cith~renovascular h7,pert=a3ion. J. Phara.Sci. 57,:'196G-195d, 309. Electronnicrosconic study of a':eae1 cortical `.:yperplJzziain Cushing'ssyndreme. Arcn. Path. 56'.::419-426, P°58. * Indicates senior ors'ole.author.r ni..i.ubr.'.IJI.:. :10. rcoa' 311. Intc:. In: i\eJ' 312.xM:ro(. 313.. * Eff'ec. synsc 16-li, 314.. * Uitr<. An. J 315:. Elect. Qacr 316. =Effect-'or 31'J'. *Ultr: Annua 31b". *Ef_'ec ultra 319. An ev235-2 320. 0%'-36vith A..^ier. 321. Antil hri-nn 322. Theeantil 323. ni.'sti 1'969. 324. * The b, carci 312-3; 325. Coopaadren, 326, x Effec Soc. 32'1. T_anor 1970. 328, Ultra 329. Ultra 330: Di-onn edl S 331. *' Ultra 54,: 7 332. *' Id'enu plasi eleco 12t36- 333.. Histoo of co 610~fi
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;10. * Paihogenesis o.`hypcrt~e.+;s'_on.:nci pathnlc3i'ochcrycsin er.u=ri.aental rcnal ir:cd'1at'.icr. La'u.. I^vcsc_. 19': 530.-13.`'.y 19Lo. 31:. Interrelheioc_chio of 1..-.-7Fatic tu-or ce11 disse:ina~i.oa. In: A'ricl, I... Ed, Prcgrersia C].iaicr.lCar.ccr,Giunc SSt:atton„ Ine., Ede•aYork, p.p..... d'--96+ 1nJ70. 31L_i:ltoc'aondri.:'_ayop.~:.hy. l.m. J. Cli; ... ?at'n. 51:.. 61P-6.J0,. 1^69_. 31;.*Eff:ect.of antily:?hcc7re serc3 c::Pa:ar.ete:.s of t~.::or yrovt.h in aa syngeneic tu^cr-hos.t syscea.?rvc..Soc. E>:p. Biol. Ned'. 131a15':-1'7, 1969.. 354. *Ultrastruc.tur.I s,:udicsin hy;.e_rtcesibn. II'.Ta::e.iaof prco.^.a~ey.. An. J', ?ith. 53: U~9-132', 1969, 315. Elkectron.microscop,ic.study, of pri.zaryreric.+lLnce11 sasce:z o` b.rain (t:icrogliona). .;,ch. Path. 37: 605-516y -9E9.. 316. * Effect of antili~phocyce se:um, on p:raaet.erso3 gro::zfi~of ::C4-=:Juced tumors. \atura.221:387-383, 1969.. 317'. * Ul.trost'ructure of h--.an.noraal ar.d ccojlas:icpr.-3tate: Ih:. ParholcgyA'nnual, ed. S,C.. Scc-,ars,. poletoa-0zr,o~,iry~ Cr~Pts,. P+.Y. 1~26, 1970. 315. *Effect of on^paramatcrsof tu~or 3:ro::t:ny histolo;;,v andultras:ructure.Czncer ? : 39-55„ 1963.. 319: An evaluation.cf rznal biopsy in preonaary toz-`+ia. OSst. S.Cyr.. 34: 235-2.411„ 1969.370.. 0%i-365. Anea ser:ally.trans.plantcole hunan~bro:.ene~genic cercf:a- witih invasive and netastaticprnoe:uia.s in i6s hamster host. ?roc. ?.mer., Assoc. Cancer Res. 1Ct 30.,,196'9. Anci1V:..ptiocy,te serum and'-llogeneic inhibition.. Ca ncer. e'.es. 30.:hn-nh,. 322. The effi~et ofthenuTber oiinjieetia:u ofzn.'a~genon eE;ou.ivanesso.fant''-ly~sphocytic saran. T.ansp'_antzfion 82 303-305s 1~69. 323. &i.stioeyoic ned'ullary.reticv.lbsis. Acta~F~matul^oica. 42: 50-57, 1969. 324'. *T'ne basal cell nature of the so-calledtra::si~t_nna1cleace,eciccarcincaa of anus as.rzvealed by electron.:z:c,oscopy,. Can.cr 29; 312-322; 1969. 325. Comparative ultra.strueturaLl studpy oi.aldcsteronc-a and non-:unccicnin3adrenal cortical edeno^a.d'reii: Pzt'n. 89.: 165-1^1,.196G°.326, * Effect of esogonou.s erythropo:etin on j=taglu.,ierul'ar cells. Ftoc. Soc. Exp., Sio1. ::_d. 132: 367-371, 1969'. 327. T,.i.,ior and host ca.lciuain hunan.colon carcino-.a. Cancer 25[:.41-4~4,. 1970. 3281 Ultrastruc'ureoichordcc.a. A'a. J. C1in.Path. 53:54~4-551', 1970. . 3329; Ultrastruvzureof rnatidomyosarc.csa. ki. J. C1i.n.2ath.53.:.555-554„ 1?7-3.. 3301 Disoaosti'c probDs:.sinvclNing r.cdal ly~ph.cmas. Iht Pa.tb.o'_coyncnual edL S.C. Som:.+ers..App,lecoc-Cenrnry-Cnofts,.t:LY. 91-129, 1970. 331. * Ultrastructure of plasna cellsia parap_o.ceinccias. i+~. .7. Clin.. Path: 54: 779-789, 1970. .332.* Idont'i~ty.and nature ofisclated lyiaphoid tu~ror:s (so-called ncdali n oer- plasia„ hanast=a and a;•eioaauocsSn-.arto-;a) a:, re'sea:ea by'aistoi.Lzc, electron nicr~oscopic.and hetero-trans.p,i:antati.on srud.ies. Cancer 25: .. 12fl6-1000, 1970. 333. HSstogenetic relationship b'etn+eencarcinoCds and :nucin-secreting.carcinomasof colon as revealed by neoerotrancrlaccacion.3rit. J. Cancer 24: 610-614, 1970.
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246 31b1icr,r.~7hy, - Ed•:rinR. Fisher, >i.D. 33:. :;,~nr;cm.ic growth andhySrid'cho_acter'.iaticn of ahynan P1:-47,3, ia untroaced h'testcrs. :rar.s.?.r.r. Assoc. Cancer ._.. 30, 1970, .335..Surther ebservabions eoncernin~ effects of act'_1•.-n~hoc•.t.eser- . entumor groc:ch:: '.d.ichspeciil re=erenceta.alioger.e!~c inhibition. Cancer Res.30: 2035-2044'., 1970. 336.*:i.stopathollogieal~ andlultrastructura'_ study, o:.allic9anei.c heoatic transpla¢ratioui.in isogeneic rats. Lab. Investigation 23.:.3 9-325y 11970. 337...°OLtrastructaral chenSes in renal ar:eriole.s andjjjuxtaole-,arular cells in hype:.tension. rv7. ileart J. 31; 125-135, 1971. 338. Conparison of conccnitant and siicccaitant'tc,r.cr i-auni,y, Proc. Soc.. Exp. Sdo1.6 Y.xd.. 135; 68-71, 1970L 339. *Electron.t:icroscopicevidence su>_3esting,the ^;•c;enous derivatibno.Pn the so~ca.1R!zd: ali.eolar soft ?.art cn,co.z: Cancer 27: 1'S0-15'9:,. 1971. 340. *Actilyr..~hocyteserca in ae;.hr.otozic serum .nepnr-ti;. Proc. Soc. Exo.. Bi~ol.. & :'ed.133: 1342-134;, 1970~ 341. Experiences iai.h 1•nphocycei-unotSerapy, in er.periceaial turror sy.stens. Cancer... 27: 77'_-731,.197.1.342. Evaluation of ah::rnora.L factor i-.li'+er r.eceeesat_onctilizing liver transalants. Cancer Research.31: 322-331„ 1871. ' 343. Erridence for a portal blood factor (.PSP), as ttie. nu:oral'.aSent in liver re3eneration. Scienc.e.171:575-577, 1971. 344. Studiesconccrni'ngrhe regicnal lys¢p'.i node in cancer. I. InUtiaoion of' icc.maity,. Cancer. 27.:. 1001w10C'+,. 1971. 345. Rod nyppathyv bioc:err:cal, i-nolug:c and moriholo0ic studies. _. \euroicgy.. In,cress. 346. Casilla_rybesen.ent cz,-.brance thicknessands the pseudo-diabetes ofnryc_arh;•.. An. J. i;ed. 51`.. 757-766s 1971. 347. *'A7cuholisa and other coceoaitants of .inac!iondrial iccLusionsinskeletaL mis cle. Am. 5.. Med. 5ci. 261: 8.5-100y 1971. 343. = Esper.ic+ental productibn~of: so-ea1!rd'.sp,ironoil.actone (aldectcae)bodies. Arch. Path. 91:: 471-478, 1971 349. Gro::rh and 1'atei.liZing ho.-:une decreases durilgg nafznoiz acid ther.a?y. Pol. Med. Sci.. & Hat:., 14: 148+153.,197.1i. 3534 *Aelationsnip of antiSodylocalizaticn to lbsioas of ne;hrotnxic serua neYhritis. :d:e?hron.8:.. 56'6-574, 1971. 351. Studies concerningthe re_.i,onal 1y-cnh n.edein~cancer: II }'g::nre,.sr.ceof.imr..unitycaicer, Iin press.... 352. Ultras¢ructur,alstud_es of~ basal.c.e11 carcicc:ca ar.d itsverd,cts•.._taco=-ts onn histog.enesis. Arch. Dac:naoo.iio,y. 104,: 132-ii0„ 1971. 353. TaS'ulat.i!onof~ fiidiys cnt'ne nusculn_" dvstronniesand in, ny,cr_onis dystr~op:nic- Aic5. Physical! ?ied. an& :2ehsb...52:. 193-200~ 197!. 354. *Local 1yr,.?:ioid response as an indexcf t:umor i Wunity..Aroh..Patn. In press. 355: *'U1Crastructurall feat.uresof aldbsteroneproducriom.. Arch. P:atn, 92: 172-179, 1971. 356. *'O1tra.structural featuresof'~,ycosis fungoides. A'm. J. Clin, Path. Ln pces:s.357: Effect of tur.or.cell coculac 6n on ciroclating 1;r.,anocytes-. Proc. Soc. E±:p, Biol.. i4ed.139: 787-792, 1;.72. 3581 Fo~.,al -scie capillaryb'asecent me:r,b:anc in juvtenileand'youngadult onset diabetes oellitns. :ietaSclism. In press.
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359. Insulin levels.,,nilld glucose into!eranc.e aed cusale sapillaryEasemenc vcmbrane. J. Clin. Endocri~n3lcoy 52tcraSolis.n. In.press. 360. *Unique coneentr_cally. 1c-,inatea; rer..branous ' inc?(uionss inc.~ypfiters- Am.J. C1 ih. :'ach. In press, 36L. *Analysis of histopatholcadc and elcctron nicrescopic detzrainancs of kersroac_ntheea and squar.ous cell carcir,oc•,a. Cancer. I, press. 362. *Commp,arative uitrascruccur.al study,of so-called renal~ adanon~a.and ' carcinoma. J• Uro1. Inp,ress. 363. Hiscochcaica'_ an.dultrastruc.tural di'.`ferenciation of spleric lipidosess with special reference to the synQro~e of the se:.-blue histiocyte. Arch. of Path. In press.. 366.~Lym?hoid; iadex in.alloUeneic inhibieion. 2r,oc. Soc.Sxp,. Iliol. :Sed: In press. 365. 17(OH): corticosteroi!d and estrogen excre.tion, with, virilizieg adrenal tunors. Hor-one. In press. 366. The ceroid cature of the.so-called.Ha.azaici-'.Zesenberg,bodies. Aa. J. C1in..Path.In.?ress. • 367.. *The fibrocytic deri~.•acicn of the so-ealLed~epi:chelioid sarc-a. Cancer,. In,press. 363: Ultrastructural features oPsubacute gra::ulcascous thyroiditis and Hashimoto's disease. Am. J. Clin, Path. In press. ., 369. *llltrastructural study of viriliaing adrenal cortical adenona. An. J.. Glin Path. In press. 370. Studiesconc^rning the rcoional L-ph,node.in.ca~cer.r II Rcspons.ee oiregional lycph node cells f:om breast and coloa car.cer patientsoo PHA s:i^~ulacion.. Cancer. In pres.s. 371. *Ultrastruccural chzn~;es inslee-etal n•_scle of muscular dyscrnphy carriers. Arch. Path. In press.
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248 CURRICULUM VIiTAE' Norman W.. Heimstra I. Biographical Data Born: October 14, 19301. Mitchell, South Dakota Married: Three children, ages 20, 18„ and 15 Present Address: University of South Dakota Vermillion, South Dakota Present Position: Dean of the Graduate School Professor of Psychology Director of Research, Director, HumaniFactors Laboratory IIi. MiLitary History Five years U.S. Navy--1948-L953 IIIi. Academic History B.A. University of South Dakota, 1955 (Psychology)'. M6A. University of South Dakota, 1956 (Psychology)', Ph.D. University of Rochester, 196A (Psychology) IV. Related Experience 1. Current Position - Dean of Graduate School, Professor of Psychology, Director of Research and Director, Human Factors Laboratory. Since July of 1974', I have been Dean of the Graduate School although I have still maintained anIactive teaching role in the Psy- chology Department, and have continued to direct the Human Factors Laboratory which is an applied psychol- ogy research unit. As Dean of the Graduate SchooL at the University of South Dakota, I have been respon- si~blie for providing, academic and administrative direction to a gradlaate school consisting of approxi- mately 1,000 students involved in programs at both the Ph.D. and Masters level. As Dean, I have also been responsible for the development of several new graduate programs. My office is also responsible for administering the General Research Fund of the Uni~- versity. Two years ago I obtained funds for and establiished an Office of Research within the Graduate Office. The Of f i~c super Level ing E As Pi cours resee suppc extei The F comp7' cepti pliec of f; den t: of 1` sourc 2'. Assi: Dakofi Psyct dire( sear(, the r was from 1963 i 3. U.S.Ii Dako anim+ monk- d_. Rese. cond, ing - 5. U.S... (195 6. Rese sity and! e lie c oped avia
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249 Office of Research, which is under the immediate supervision of an individual trained at the Ph.D. level, is responsible for assisting,faculty in obtain- ing,external research support. As Professor of Psychology, I teach at least one course each semester and direct graduate student research. I also maintain several ongoing externally supportediresearch. I also maintain several ongoing externalily supported research projects. The HumaniFactors Laboratory, which I direct,, is a completely externally funded operation (with the ex- ception of some faculty salaries) which conducts ap- plied psychologicali research. At present, it consists of five Ph.D. level researchers, ten graduate stu- dents who are working for Ph.D. degrees,, and a staff of 15. We maintain an operating,budget from outside sources of about one-half million dollars a year. 2. Assistant Professor to Professor, University of South Dakota (1963 to present)i. As a faculty member in the Psy,chology, Department, I have taught the usual courses, directed'Ph.D. and M.A. level graduate student re- search, served on numerous committees, etc. Possibly the most significant achievement during this period was the development of the Human Factors Laboratory from a one faculity, one graduate student operation in 1963 to a sophisticated research facility. 3. U.S.P.H.S. Postdoctoral Fellow, University of South Dakota (1i961-1963'). Worked in liaboratory on various animal behavior projects. Conducted studies with monkeys, rats, fish, and other animals. a;. Research Scientist, HumRRO (1960-1i961). Designed and conducted several investigations dealing with train- ing of Army helicopter and fixed wing aviators. 5. U.S.P.H.S. Predoctoral Felliow, University of Rochester (1959-19fi0)1. Completed Ph.D. degree. 6. Research Associate, HumRRO (George Washington Univer- sity )(1i957-1959). Responsible for the development and evaluation of a new approach to teaching basic electronics to low aptitude personnel. Also devel- oped and helped conduct a world-wide servey of Army aviators.
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250 7. Teaching,Assistant, University of Rochester (1!956- 1957)',. Was responsible for several sections of in- troductory psychol'ogy class. 8. ResearchlAssistant, University of South Dakota Pri- mate Laboratory (1955-11956). Assisted on several projects concerned with the effects of irradiation on various aspects of behavior of monkeys. V. Membership inlOrganizations, ConsuLtantships, Advisory Panels (Past and Present) APA, Human Factors Society American ASsociation for Automotive Medicine Sigma Xi (President, South Dakota Chapter, 1965-11966) Phil Beta Kappa Highway Research Board Liaison Representative--University of South Dakota Member of Special Committee 11--Driving,Simulationy High- way Research Board, National Academy of Science Consultant--Department of Army (Design and Measurement of Performance) Advisory Panel--American Institute for Research Editorial Board--Human Factors VIi. Academic Experience Courses Taught: Introductory Psychology Physiological Psychology'(undergraduate), Seminar in Physiological Psychology (graduate)'. Industrial Psychology (undergxaduate)' Personnel!Selection & Training ('graduate) Human Factors Psychology (graduate), Seminar in Accident Prevention Research (graduate), Psychology in Environmental graduate) Today's World (undergradlaate). Psychology (undergraduate & Ph.D, Dissertations Directed - 17 M.A. Theses Directed - 47 VII. Research Activities 11. Research Grant Activities: Since joining the faculty at the University of South Dakota, I have been re- .k.
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HEW' U.S. Bureau of Roads South Dakota Department of Highways Air Force office of Scientific Research U.S. Army Medical R&D Command The Councilifor Tobacco Research-U.S.A. Automotive Safety Foundation Sport Fishing Institute Bureau of Sport Fisheries and Wildlife (With R. T. Davis and J. P. Steelie) Effects of various food deprivation schedules on the dis- crimination learning performance of monkeys i~r- radiated with,X-Ray irradiation. J_. Psychol., 1957, 44, 271-281. (With G. Newton) Effects of early experience on the response to whole body x-irradiation. Canad. J. Psychol., 19601, 14, 111-119. (With G. Newton) Effects of prior food competi- ti~on on the rat's killing response to the white mouse. Behaviour, 1961, 14, 95-102. Fffects of chlorpromazine on dominance and'.ag- gressive behavior in the rat. Behaviour, 1961, 233-244. 18, 313-321. Social influence on the response to drugs: 11. Amphetamine sulfate. J. Psychol., 1962'„ 53, - - Effects of amphetamine sulfate on the behavior of paired rats in a competitive situation. Psychol. Rec., 1962, 12, 25-34. Social influence on the response to drugs: II. Chlorpromazine and ironiazid. Psychopharmaco- logia, 1962, 3, 72-78.
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252 (With A. McDonald), Social influence on the re- sponse toldrugs: III. Age factors in the re- sponse to amphetamine sulfate. Psychopharmaco- logia, 1962, 3, 212-218. (With A. McDonald) Social influence on the re- sponse to drugs: IV. Stimulus factors. Psychol. Rec., 1962, 12, 327-330. (With R. T'. Davis) A simple recording,system for the direct observation technique. Animal Behaviour, 1962, 10, 208-210. (With T. M. Mast)~ Effects of prior social ex- perience on amphetamine toxicity in mice. Psychol. Rep., 1962, 11, 809-812. (With T. M. Mast and1L. L. Larrabee) Effects of' fatigue on basic processes involved in human operation performance: I. SimpLe vigiliance and target detection. Highway Research Record, 1963, 55, 17-20. (With A. L. McDonald) Modification of aggres- sive behavior of green sunfish with D-Lysergic acid diethylamide. J. Psychol., 1964, 57, 19- 23. - - (With T'. M. Mast) Effects of fatigue on vigil- ance. Ji. Engineering Psych., 1964, 3(3), 73-79:. ((9ith H. F. Jones) Ability of drivers to make critical passing judgments. J. Engineering Psych., 1964, 3(4), 117-122. (With A. L. McDonald)i Agonistic behavior in several! species of fish. Psych. Rep., 1965, 16, 845-850. A further investigation of the development of mouse killing,in rats. Psychonomic Sci., 1965, 2, 179-180. (With A. L. McDonald) Social influence on the response to drugs: V. Modification of behavior of non-drugged rats by drugged. Psychopharmaco- logia, 1965y 8, 174-18-0. ~ ~ 3'4-L21 0
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253 (With S. Sallee) Effects of early drug treat- ment on adult dominance behavior in rats. P~- chopharmacologia, 1965, 8, 235,240. (With N. R. Bancroft and A. R. DeKock) Effects of smoking upon sustained performance in a sim- ulated driving task. In H. B. Murphy (Ed!.)',. The effects of smoking on the central nervous system. Ann. N. Y. Acad. Sci., 1967. (With V. S. Elli;ngstad and1A. R. DeKock) Effects of operator mood on performance in a simulated driving task. Perceptual and Motor Skills,, 1967, i25, 729-735. ^ (With A. L. McDonald and D. K. Damkot), Social modification of agonistic behaviour in fish. Animal Behaviour, 1968',, 16, 437-441. (With V. Ellingstad) Velocity-time estimation as a function of target speed and conceal2nent extent. Human Factors, 1969, 11, 305-312. (With J. Nichols and G. Martin) An experimental methodology for analysis of child pedestrian behavior. Pediatrics, 1969, 44, (part 2) 832- 838. Effects of "stress fatigue" ' on performance in a simulated driving situati;on. Ergpnomics,, 1970, 13 (2) , 209-2118:. (With V., Ellingstad)i Performance changes during sustained operation of a complex psychomotor task. Ergonomics, 1970, 13(6), 693-705. (With H. D. Warner) Effects of intermittent noise on visual search tasks of varying complex- ity. Perceptual and Motor Skillis, 1971, 32, 219-226. (With H1. D. Warner) Effects of noise intensity on visual target-detection performance. Human Factors, 1902;, 14(2), 177-181. (With M. A. Hofmann) Tracking performance with visual,, auditory, or electrocutaneous displays. Human Factors, 1972', 14(2),, 127-134. -6-
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254 (With H. D Warner) Target-detection performance as a function of noise intensity and task diffi- culty. Perceptual and Motor Skills, 1973, 36, 439-44i2. - - The effects of smoking on mood change. Iin W,. L. Dunn ('Dd.) Smoking behavior: Motives and ilncen- tives. Washington, D.C.: V. H. Winston & Sons, 1i973. (With R. L. Lucas and ID. K. Spiegel) Part-task simulation training of driver's passing judg- ments. Human Factors, 1973',, 15, 269-274. (With G. L. Martin) The perception of hazard by children. Journal' of Safety Research, 1973, 5(14), 238-246. (With G. L. Martin) Consumer input for child safety programs. Journal for School Health, 1974, XLIV(2)!, 80-$2~ (With L. H. McFarling)' Pacing, product complex- ity, and task perception in simulated inspection. Human Factors,, August, 1975, 17'(4),, 361'-367. b. Technicali Reports and Final Progress Reports: Because of the nature of applied psycholog;ical research, much of the funding is in the form of contracts which require publication of "tech" reports. Reports from these t_vpe projects are liisted bellow. (With S. J. Goffard, R. S Beecroft, and J. W. Openshaw) Basic electronics for miniimally, qual- ified men: An experimental evaluation of a method of presentation. HumRRO Tech. Report #61, 1960. (WithiN. B. Louis and'A. Young) Survey of op- erational fixed wing aviators flying activities. HumRRO Tech. Report #76, 1962. (With T. M. Mast and D. K. Spiegel) The relia- tionship between operator mood and performance in a simulated driving task. Technical Report No. 2, Human Factors Laboratory, University of South Dakota, 1963. (Prepared for the South Dakota Highway Department.)
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255 (With T. M. Mast and H. F. Jones) The effects of fatigue on performance in a simulated driving, task. Technical Report No. 3, Human Factors Laboratory, University of South Dakota, 1964:. (Prepared for the South Dakota Highway Depart- ment.)' (With H. F. Jones) An investigation of the re- lationship between performance on a"speed anti- cipation" test and driver performance. Techni- cal Report No. 4, Human Factors Laboratory, Uhi- versilty of South Dakota, 1964. (Prepared for the South Dakota Highway Department.) (With H. F. Jones) Signal detection as a func- tion of location. Technical Report No. 5, Human Factors Laboratory, University of South Dakota, 1965. (Prepared for the South Dakota Highway Department.) (With A. R. DeKock) Effects of sustained per- formance on differential angular velocity judg- ments. Technical Report No. 6, Human Factors Laboratory, University of South Dakota, 1966. '((Prepared for the South Dakota Highway Depart- ment.Y (With V. S. Ellingstad) Performance decrement during 15 hours operation of a complex psycho- motor task. Technical Report No. 7, Human Factors Laboratory, University of' South Dakota, 1967. (Prepared for the South Dakota Highway Department.) (With D. K. Damkot and N'. G. Benson) The effects of silt turbidity on behavior of juvenile large- mouth bass and green sunfish. Technical Paper, Bureau of Sport Fisheries and Wildlife, 1968. (With V. Ellingstad) Estimation of movement as a function of target speed, display distance,, andiconcealtrnent distance. Technical'Report No:. 8,, April, 1968:,,Human,Factors Laboratory, Uni- versity of South Dakota. (Prepared for the South Dakota Highway Departr[ent.) , -8- I r a I 11 I: il I a Bf
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256 (With G. Martin) Perception of hazardibg young children. Technical Report, Human Factors Lab- oratory, University of South Dakota, 1970. (With C. R. SCoughton), The effects of smoking on peripheral movement detection. Technical Report, Human Factors Laboratory, University of South Dakota, 1973'. (Prepared for the U.S. Army Medical Research and Develiopment Command, Wash- ington, D.C.)' Year 1. (With C. R. Scoughton) The effects of smoking on peripheral movement detection. Tiechnical Report, Human Factors Laboratory, University of South Dakota, 11975. (Preparedifor the U.S. Army Medical Research and Development Command,, Wash- ington, D.C.) Year 2'. (WithiJ. L. Arnold)' Effects of smoking depriva- tion on group problemisol'ving processes. Tech- nical Report, Human Factors Laboratory, Univer- sity of South Dakota, 1975. (Prepared for the Council for Tobacco Research, U.S.A., New York, New York). (With J. L. Arnold)i Effects of smoking depri- vation on risk-taking behavior. Technical, Re- port, Human Factors Laboratory, University of South Dakota, 1976. (Prepared for the Council for Tobacco Research, U.S.A., New York, New York. ) (With S. T. Breidenbach and J. L. Arnold) The effects on smoking on time estimation perfor- mance. Technical Report, Human Factors Laborar tory, University of South~Dakota, 1976. (Pre- pared for the U.S. Army MedicallResearch and Development Command, Washington, D.C.) Year 1. c. Books Heimstra, N. W. (Ed,.), In'ur Control in Traffic Safet . Springfield, I11.: Charlies C. Thomas, 1970. Heimstra, N. W. an&Ellingstad, V. S., Human Behavior: A_ S s~tems Approach. Monterey: Brooks Cole Pub~li.sFiTing Co., April, 1972. I -9-
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257 Heimstra, N. W. and McDonald, A. L., Ps chol'o and Contemporary Problems. Monterey: Brooks Y Cole Publ!ishing,Co., February, 1973. Ellingstadi, V. S. and Heimstra, N. W., Methods in the Study of Behavior. Monterey: Brooks, Cole Publishing,Co., October, 1974. Heimstra, N. W. and!EmFarling, L. H:., Environ- mental Psychology. Monterey: Brooks/Cole Pub- lishing Co., August,, 11974 (being revised for a second edition). -10- 1 0 C E rI Va 0 us 0
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258 CURRICULUM VITAE GR POST. ADU MOSER, KENNETH MILES Consultantitc Beth d Mc Date of Birth: April 12, 1929 Place of Birth: Baltimore, Maryland Social Security No.: 220-20-8585 Married: June 17, 1951 - Sara (Folk) Children: Gtegory; May 11, 1955; Kathleenj , February 9, 1957; es a, Assaciate Prc Medicine, W Auociate Prc Margot, June 18, 1959; Diana Joyce, Decemb'er26,,1963. School of Me EDUCATION: HcverFord College, Phi Beta Kappa, 1950, Director, Pul Sch l f M Clemetine Cope Fellow, A.B. Joh'ns Hopkirs University Medical School, M.D. 1954 oo o e Consultant ir POST GRADUATE TRAINING, TEACHING ASSIGNMENTS, STAFF APPOINTMENTS: Medical Dire Interrmshiq, District ofl CoVumLiia General Hospital, Geongetown University 1954-55 GrossmoMr C, Medical Service, Washington, D.C. Resident, Internal Medicine, Georgetown University Medical Service, District of Columbia General Hospital, Washington„ D.C. Resident, Pulmonary Disease,, Pulmonary Disease Division, 1955-56 1956'-57' Director, lUC Professor of h Medicine, G District of Columbia General Hospital, Washington,, D.C. Resident, Internal Medicine, Georgetown University Medical Center, 1957-58 Washington, D.C. 1 Chief Resident, Medicine, Georgetown University Medical Service, District oflColumbia General Hespital, Washington, D.C. lnstructor in Medicine and Preventive Medicine, Georgetown,lDniversity 1958-59 1958-61 I. School of Medicine, Washingtonj D.C. Head, Pulmonary Disease Section, Nationall Naval Hospital, 1959-61 Bethesda, Maryland Chief, Pulmonary Division, Georgetown UhiversiFy Hospital,, 1961-68 Washington, D.C. Chief, Pulmonary Section, Georgetown Clinical Research Institute, 1961-66 Office of Aviation Medicine, Federal Aviation Agency,, Washington, D.C. Consultant in Pulmonary Disease, U.S. Naval Hospital', Bethesda, Maryland 1961-68 Assistant Professoa ofMedici.ne,. Georgetown University5chool of 1961-67 Medicine, Washington, D.C.
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PCST GRADUATE TRAINING, TEACHING ASSIGNMENTS, STAFF APPCINTMENTS; Cont'd. Consultant to the Clinical Center, National Institutes of Health, Bethesda,.. Maryland! Associbte Professor of' Medicine, Georgetown University School of Medicina,, Washington, D.C. Associate Professor of Medicine, University, of Califamia, San Diego,. School of Medicine, La Jolla, CaliFornia Director, Pulmonary Division, University of California, San Diego, School of Medicine, La Jmllay California Consultant in Pulmonary, Disease, U.S. Naval Hospital, Son Diego, Calif. Medical Director, Inhalation Therapy and Biornedical Technology Schools, Grassmant College, San Diego, Califbrnia Director, UCSD-NHLI Pulmonary Specialized Center of Research Professor,of Medicine, University of California, Son Diego, School of Medicine, La Jollby, California ~
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MEMBERSHIPS and OFFICES; ARTICLES: Americon Physiologioal Society' (1): Moser, Fellow, American College of Physicians Fellow, American College of Chest Physicians (Member, Education Committee, 1973- ) South'ern Society for Clinical Investigation (1965-69) (2)' and An Moser, Western Society for Clinical Research (1969-present) .2 Cor Pu Society of Nuclear Medicine (1966) Editorial Board; Chest (1970- ) (3)', Luchsir EditariallBoard; Archives of Ineernal'Medicine (1972-75) relatioi EditoriallBoard,. American Review oGspirato . Diseases ciency California Thoraeic ociety (Chairman, Scientific Council, 1971-73; President-elect, 1976), Medical Society of Son Diego County. (4)'. Moser, Member, FDA Cardiovascular and RenallAdviaory Committee (1968-72) National Advisory Board, National Society of Cardiopulmonary Technologists AmericaniHeart Association (Executive Committee, Council on Thrombosis, 1974- )' American Thoracic Society (Chairman, Fellowship Committee, 1971-72; I 5) Capobl Dis, 7! Moser, Chairman, Medical Education Committee,, 1973-) Americon Federation for Clinical Research (Past President, D.C. Chapter)i Association of American Medical Colleges (6)' Approo Luchsir American Association for the Advancement of Science Member, Board of Directors, D.C. Lurg Association,(lfce-PresidenY, 1967-69) Cardi oi 35:52, Member, Board of Directors, Lung Association of'San Diego and'Imperial Counties (President, 1971-73)' (7) ~ Luchsir American College of Chest Physiciars,, Potomac Chapter (Vice-President, 1965-66; Diagno President, 1966-67) } Member, Advisary, Panel N6tional Heart Biood VessellLung and Blood'Program, National Institutes of Health; Chairman, Venous Thrombosis Task''Group (8) Bulletn McCuii Member, FDA Pulmonary and Allergy, Advisory Committee (1972-74), California Lung Association (Member, Board of Directors, 1974'- ) of the , 4:42-5: Membery Pulmonary'Subspecialty Board, American Board of Internal Medicine (1974- (9) Moser, (10) Man . Moser,, and EfF 1959. (11) Moner, (12) Fibrino Moser,, in Acu'
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261 PUBLICATIONS ARTVCLES: (1) Moaer, K.M.: Intiamuscular Injection of Trypsine Its Valle as a Thrombolytic and Anti-inflammatory Agentl. New Engl J Med 256:258-263, 308'-309> 1957. (2) Moser, K.M. and Shea, J.G.: The Relationship Between,Pulmonary lnfaretion, Car Pulmonale, and Sickle States. Am JiMedo 22:561-579; 1957. (3) Luchsinger, P'.C., Moser, K.M., Buhlman, A., and Rossier, P.HI.; The Inter- relationship Between Car Pulmonale, Capillbry Bed Restriction Diffusion Insuffi- ciency for Oxygen in tfie Lung. Am Heart J, 546106-117y 1957. (4)' Moser, K,M. and McCuiston, C.F.: Achalasia (mega-esophagus)i A Condition Capable of Simulating MediastinaLNeoplasm. Am.Rev of Tuberculosis and Pul Dis, 76:480-490;,1957. (5) Moser,. K.M.: Thrombolysis andFibrinolysis(Plasmin);-ANewTherapeutic Approach',toThromtioembolism. J.A.M'.A., 167:1695-1704, 1958. (6) Luchsinger,.P.C., Katz,.S., McCormick, G.F.,.Donohoe, R.F.,and Moser, K.M.: Cardiorespiratory Studies in Hamman$ich Syndrome. Diseases of the Chest, 35:52-61, 1959. Luchsingery P.C., and Moser, K.M.: CorPulmonale: Part Ii Etiologic and Diagnostic DifferencasBetween Anatomic and Functional Forms. The Heart Bulletin, 82-5, 37-39, 1959'. (8)', McCuiston, C.F.,, and Moser, K.M.: Studies in Pericarditis: I. Differentiation of the Acute Idiopathic Form From ThaYOccurring in Disseminated. Am J Cordial , 4:42-55, 1959. (9) Moser, K.M6:. Effects oflntravenous Administration of Fibrinolysin (Plasmin) in~ Man. Circulation, 20(l):42-55, 1959. (10) Moser,, K.M.: Intravenous Administration of Fitirinolysin: ItsSystemic.Toxicity and Effect.Upon Components of the Coagulation Mechanism. Angiology,. 10:253-258, 1959. (11) Moser, K.M.: Clinical Observations in Thromboembolic Disease Treatfd with Fibrinotysin. Angiology, 10i319-331, 1959. (12) Moser, K.M., Hajjar,,G.C., and Sulavik, S.6.: Fibrinolysin (Plasmin) Therapy in Acute Deep Thrombophlbbitis: A,Controllad S'tudy. Circulation, 21:337-352, 1960. t M 0
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262 PUBLICATIONS ARTiICL5S, (Continued): (13) Moser, K.M'., Luchsinger, P.C., and Katz, S.: Pulmonary and Cardiac Function in Sickle Cell Lung Disease: Preliminary Report. Diseases of the Chest, 37(6)6637-648, 1960. (14) Moser, K.M., and Hajjqr, G.C.: The Combined Use of Flbriholytic and'Anti- coagulontlAgents: Laboratory and Clinical Considerctions. Am J Cardioll, 6:496'-502„ 1960. (15) Moser, K.M., and'Hajjar, G.C.: The Effect of IntramuscularTrypsin in Acute Bacterial Pneumonia. Am J Med Sci, 24(4):423-435, 1961. (1'6), Moser, K.IvI., Hajjar, G.C.,, and Sulbvik, S'.B.: Fibrino6ytic Thercpy in Acute Deep Thrambophlabitis: Interim Reportlof a Controlled'Study: Angiology, 12(5)d195-200, 1961. (17)' Haflar, G.C., Whissen, N.C., and Moser, K.M.: Diurnal Variation in Plasma EuglobulSn Activity and Fibrinogen Levels: Preliminary Report. Angiology, 12(5):160-164, 1961. (18) Moser, K.M.: Throm6olytic Activity and Related Phenomena. Thrombosis and Diathesis Hem (Suppl)t 6:305-315, 1962. (19) Moser, K.M.: Cun•entlStatus of Clot Dissolution Therapy. GP, 26(5):95-102, 1962. (20), Moser, K.M., Pen-y;, R.B., and Luchsinger, P.C.: Cardiopulmonary Consequences oflPyrogen-lnduced Hyperpyrexia in Mon. J'Clin Invest, 42(5)f626-634y 1963. (21) (22) (23) MeTommmany; J'.R., Moser, K.M., and Houk, V.N.: Disseminated Bone Tuber- culosis: Review of Literature and Presentation of an Uhusual Case. Am Rev Resp Dis,$7(6):889-895, 1963. Houk, V.N., McClenathan, J.E.,,Hufnagel, C.A., and'Mosen, K.M6: Chronic Thrombotic. Obsttuetion of Mc.jor PuImonaryArteries. Am J af 1Sted,. 3(2):269-282,. 1963. Houk, V.N., and Moser, K.lv1.: Cortieosteroid~Theropy.for Boeck's5ercoid. J-A.M.A. 185(12):973-975, 1963. (24) Moser, K.M., and Hajjar, G.C.: Thrombolytic Therapy: Progress and Problems. Sobretiro db Memorias del fV Cangreso Mbndial de Cordialogia, 4;-B:3-8,, 1963. ARTI (26) I (32), 1 (357'. (37)
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ARTICLES, Continued: 263 PUBLICATIONS (25)I Moser, K.M.: THerapeutic Fibrinolysis in Angiopathies. Verliandlungen des IIw Intemationelen Gesprachs uber Angiologie, Verlag Darmstadt, 213-218~ 1963. (26), Hbuk, V.N.,,and Moser,.K.M.: Unusual Presentationsof'PulmonaryHistoplasmosiss Med Ann Dist~of Col; 33(10):467-476y 1964. (27) (28) (30) Moser, K.M., Rhodes, P.G., and Hufnagel, C.C.: Chronic Unilateral Pulmonaryr Artery Thrombosis: Successful Thromboend6rtereetomy WitH Thitty-MontH Follow-up Observation. NlEngl!J Med, 272:1195-1199, 1965. Moser, K.M., Houk, V'.N.,, Jones, R.C., and Hufnagel, C.C.:: Chronic Massive Thrombotic Obstruction of the Pulmonary Arteries: A'nalysisof Four Operated Cases. Circulation, 32:377-385, 19656 .ouk, V.N., and Moser, K.M.: Pulmonary Cryptococcasi's: Must All Receive Amphotericin B? Ann Intem Med, 63(4);583-596,, 1965., Moser, K.M'., and RHodes,P.G.c Acute Effecis of Aerosolixed'Acetylcysteine Upon Spirometric Measurementss in Subjects With,amd Without Obstructive Pulmonary Disease. Diseases of the Chest, 49(4):370-373, 1966'. (31) Moser, K.M., and'FreyyM.B.: Comparison of Caseinol!ytic and Fibrinolytic Assays For Plasmin (Fibrinolysin), in "Fibrinolytic Agents."' THrombosis et DiatH.Haem, 25025'[-271,, 1966. (32) Moser, K.M. and Hajjar, G.C.: Age and!Disease-'telated Alterations in Fibrinogen- Eug/bbulin (Fibrinolytir) Behavior. Am J Med Sci, 2511(5):536-544, 1966. (33) Moser, K.M.: The Comple Fibrinolyticisti A Study in Septophrenia. Fed. Proc. 25(l):94-99, 1966.. (34) Rhodes, P.G.,, and Moser,, K.M.: Sources of Error in Oxygen Tension Meesurement:.. J Appi Phys, 21(2):729-734, 1966 (35) ' (37) Moser, K.M., Tisi, G.M'.,Rhales,.P.G.,,L'andis, G.A., and Miale, A.Jr.: Correlation of Lumg Photoscans With Pullnonory AngiograpHy in Pulmonary Embolism. Am J Cordial, 18(6):810-820, 1966. Moser, K.M., and Hajjcr, G.C.: Effect of Heparin on the One-Stage Prothrombin Time: Source of Artifactual 'Resistance" to Prothrombinopenic Therapy. Ann lotem Med, 66(6);:1207-1213, 1967. Strickland,,G.T., andMoser.,.K.M.c Sarcoidosis With Landry-G uillhin-Barre Syndrome and Clinical Response to Conticosteroids. Am J!Med, 43(i1);:131-135, 1967. i tH I
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264 PIJBLICATIONS ARTICLESy Cantinued: ARTICLES, (38) Moser, K.M., and'Miale, A., Jn.: Interpretive Pitfalls in Pulmanory Photo- (49) M scanning. Am J Med, 44e366-376, 1968. ,7) fa 56 (39) Tisi, G.M., Twigg,,H.L., and Moser, K.M.: Collapse of Left'Lung Induced byArtificiai Airway. Lancet, 1t79i-793, 1968. ~ (50) Po (N,0) Tisi, G.M., Landis, G.A,,, Miale, A., Jr,., and Moser,K.M.: Caucntitation of Ar Regional Pulmonary Blood Fiow: Validity ond Potential i Source of Error. Am Rev ' (51) Mc( Resp Dis, 97:843-BS0, 1968. on., (41) Gluck,. M'.C.,, and Moser,. K.M'.:Harartoma of the Lung Presenting,.as a in Mkdiastinol!Mass. Arn Bev Resp Dis, 98t281-286,, 1968. (52) BuO (42)', Miale, A., Jr., Landis, G.A., and Mosee, K.Mu Lung Scanning with the in Scintillation Camera. Proceedings of the Symposium in Nuclear Medicine--Ih (53) Mo (43) Current Status in f4ledical.Practice (pp246-280), U.S. Department of Commerce, Springfieltly Virginia,, 1968. Hansany+, P'.G., Rius-Gortiga, J., and Moser, K.M.: Acute Hemodynamic (54) of I PuE G I: Consequences of Ligation of the Inferior Vena Cava.J Thorac Cardiovasc Surgy 57:442-449, 1969. Ver (55) Shil' (44) Foti, P'.R., and'M.aser, K.M.c Laboratory Guides to Scalene Node or Liver men (45) Biopsy in Suspected Sarcoidosis. Am RevResp Dis, 90:6'10-613, 1969. Shibel; E.M., Landis, G.A., and:Moser, K.M.; Inhalation Lung Scanning (56) THo Ashl Evaluation: Radioaerosoi Versus Radio-Xenon Techniques. Dis of{hest', 56: 284-289, 1969. of A Mec (46). Shibel, E.M., Tisis, G.M., and Moser, K.M.; Pulmonary Photoscon- (57), Lcnc. ' Roent§enographic Comparisons in Sarcaidosis. Am J Roentg Qad Ther and Nucl Medy 106:770-777, 1969. in tl Aml (47) St(emh'olm, M.R., Landis, G.A., Marcus, F.I., Miale, A., Jr., Moser, K.M.: (58) Mos. 48) Perfusion and Ventilation Radioisotope Lung Scansin.Stenasis oftfie Pullnonary Arteries and Their Branchea. Am Heart J'78:37-42; 1969. Cerbonell, A.M,, Landis, G.A., Miale, A., Jr. and Moser, K.M.: 59) Reve (Prel Most , Construction and Testing of a Thormc-Lung Phantom to Aid'in Scintiphotograph interpretotion. Investigative Radiology} 4(4):275-285, 1969. of Pv Scin-
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265 PUBLICATIONS ARTICLES, Continued: (49) Moser, K.M., Nublby L.E., and Torzewski, D.F.: P.actical''Computer Program far Routine Spirometric Testing Using the "Time-Sharing" Concept. Dis Chest, 56'e92-97; 1969. (50) Foti, P.R., and Moser, K.M.: An EffectiveSimple Technique for lndwelling, Arterial Cannulation. Angiology 20(B):439-445y 1969. (tT)' Masery K.M., Hananyi; P.,Rius-Garriga, G., Guisanp M., Landis, G.A., and Miale, A., Jr.: Assessment of Pulmonary Photoscanning and Angiography in &perimenthl PulmonaryEmbolism. Circulation 39;663-674, 1969'. (5'<) Butfer, E.H., Moser, K.M., and'Kot, P.A.: Distribution Volume of Isoproterenol in the Isolated Lung of the Dog. J of Leab ond Ciin Med; 74(1)c129-137,, 1969. (53)', Moser, K.M.: In Vivo TesHng,of Synthetic Fibrinoiytic Agents. Chemical!Control! of Fibrinolysis. Joseph M. Schor, Editor. John Wiley,and Sans, Inc. - Interscience Publishers. New York, NY, 1970. (54) Gluck,.M.C. and Moser,. K.M.: Pulmmary,Artery.Agenesis. Diagnosiswith. Ventilation and Perfusion Sc in ti photography. Circulation, 41h859-867y 1970. (55) Shibel, E.M'., and Moser, K.M.s The Relbtionship Between Spirometric Measure- ments and Arterial'Blbod Gas Analysis in Patients with Chronic Airflow Obstrvction. Thorax, 25:598, 1970. (56), Ashbum, W.L., Guisan, M., and Moser, K.M.: Digital and Analog Processing of Anger Camera Data with A Dedicated, Computer.{ontTOlled System. JiNbel Med, 11:680+-688, 1970. (57) Longo, A.M'., Moser, K.M., and Luehsingery P.C.: The Role of Oxygen Therapy in the Rehabilitation of Patients with Chronic Obstructive Pulmonary Disease. Am Rev Resp Dis, 103:690-697, 1971. (58) Moser, K.M., Harsany,i, P., Harvey-5mith'y W., Durante, P., and Guison, M6:. Reversible Interruption of Ihferior Vena Cava by Means of a Balloon Catheter (Preliminary Report). JiThorac Cardiovasc Surg, 62:205-212, 1971. (59) Moser, K.M., Guisan, M., Cuomo, A.J. and Ashbum, W.L.: Differentiation of Pulmonary. Vascular From.Paremchymal Diseases by. Ventilation/Perfusian Scintiphotography. Ann Int Med, 75:597-605, 1971 .
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266 PUBLICATIONS t ARTICLES, Continuedc ARTICLES, C (60) Moser, K.M~: TB-No Longer an Educational Dropoutl. National Tuberculosis and Respiratory Disease Association, Bulletin. p 11-13, October, 1971. (70)', Cuo Cap (61), Moser, K.AiS.:Antithrombotic and ThrombolyHc Drugs.. SearchFor New.Drugs. Alan A. Rubin, Editor, Marcel Dekker, Inc., New York, NY 1972. J Ai (71) Ung (62) Tisi, G.M., Trummer, M.J., Cuomo, A.J'., Ashbum, W'.L ., and Moser, K.M.: Lang Term Autotransplanted Canine Lungs: Baseline Ventil6toryand Hemodynamic Arcl Function and Vasculbr Response to Augmented Pulmonary Blood Flow and Alveolor Anoxia. J Appl Physioll, 32!113-120, 1972. (72) htm. in C Intn (63)! Bcrtimmo, E.E.,, Jr.,. Guisan, Ms,, and Moser,K.M.:. Pulmonary Involvement in Fabry's Disease: Fact or Fancy?' Am J Med, 53:755-764, 1972. (T)', Mos. Scin (64): Guisant M., Tisi, G.N1,, Ashbumj W.L., and Moser, K.M.: Washout of 133Xenon Gas From the Lungs: Comparison with Nitrogen Washout'. Chest. 197.• (74) i Moss 621146-151, 1972. and, (65) Maser, K.M.: PulmonaryRadioisotopic and'Radiographic Technics: Whct They Show, Do Not Show, and Why. CllnicallUses of RadionucIid'es: Critieall Embc Comparison With Other Techniu. Francis A. Goswitz, Gould A. Andrews and Manuel Viamonte,, Jr.,. Editors. U.S..Atomic Energy{ommission. Oak Ridge, (75) Mose Chro Tenn. 1972. (76) Liebc (66) Moser, K.M., Guison, M6, and Bartimmo, E.E.Jr.: Resolution Rates of Experimentvl'Venous Thromboemboli. PulmonaryTflromboembolism, Kenneth M. Dysp Moser and Myron Stein, Editors. Yearbook Medical Publishers, Chicego, Illinois, (77) CooL 1973. Rate (67), Ashburn, W.L., and Moser, K.M.: Pulmonary Ventilation and Perfusion Scan- ning in Pullnonary Thromboembolism. Pulmonary Thromboemboliim. Kenneth M. Moser, and Myron3tein, Editon.. Yearbook MedicallPublisher,.Chicogo,. Illinois,. (78) Hala: Mose ofPh 1973. Surg, (68), Moser, K.N1., Shibel, E.M., et al: Respiratory Stimulation with Introvenous Daxapram in Respiratory Failure: A Double-Blind Cooperative Study. New Engl (79) Reppe tion < J Med;,288:427-431, 1973. 3:12- (69). Minh, V.D.,, and Moser,, K.M.: lvlonoradicular Electrophrenic Respiration. ($0) Hcbei J Appl Physiol, 34:504-507, 1973. Ashbi Ttach
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267. ARTICLES, Contiiued: PUBLICATIONS (70) Cuomo, A.J., Tis~i G.M. and Moser, K.M'.: Tfle Relbtionship of Diffusing Capocitiy and Km to Alveolar Volume and the Ptrtition of Pulmonary Perfusion. J Appi Physial 35:129-135, 1973. (71) Unger, K.M. and'Moser, K.M.: FatallCompliaations of Transtracheal Aspiration. Arch Int Med, 132:437-440, 1973. (72): Moser, K.M., Shibel, E.M., and Beaman, A.J.: Acute Respiratory Failure in Obstructive Lung Disease: Long-Term Survival After Treatment in an Intensive Care Unit. JAMA, 225:705-707, 1973. (73): Maser, K.M., Longo, A.M., Ashbum, W.L., and'Guisan, M.: Spurious ScintiphotographicRecurrence of POlmonaryEmboli.M'Am J Mad, 55:434-443, 1973. (74)1 Moser, K.M., Guisan, M., Bartimmo, E.E.,.Longa,,A.M., Harsanyi,.P.G.,and Chiorazzi, N.: In-Viwo and Post Mirtem Dissolution Rates of Pulmonary Emboli and Venous Thrombi in the Dog. Circulbtion, 48:170-178, 1973. Moser, K.M., and Brounwald, N.S.: Successful Surgical Intervention in Severe. Chronic Thromboembolic Pulmonary Hypertension. Chest, 64:29-35, 1973. (76)i Liebow;, A.A., Moser,, K.M., and Southgate, M6TI.: Rapidly Ptogressive Dyspnea in a Teenage Boy. JAMA, 223:1243-1253'y 1973.. (77)i Cooleyy, W.L.,and:Maser, K.M'.:.. A.Simple SignalProcessor for a Respiratory ~ Rate Monitor. IEEE Transactions on Biomedical'Engineering, 10:309-3'10; 1973. (78) Halaszy N.A., Catonzaro, A., Trvmaer, M.JS,,Tisi, G.M., Salt:stein, S.L., Moser, K.M., and Hutchin, P.: Transplantation of the Lung. Correlation of'Ph''ysiolbgic, IMmunologic and Histologic Findings. J Thorca{ardiovasc Surg, 66:581-587, 1973. Reppeto, N'_P'., Uhger, K.M., and'Moser, K.M.: Changes in Oxygen Consump- tion~.and P50 in COPD Patients AfterRehabilitation Program. THe NSCPT Analyzer,. 3:12-14'1 1973. Habermcny P.B., Green, J.P., Archibald, C., Dunn,D.L.,.Hbrwitz,.S.R., Aihbumy W.L., and Moser, K.M.: Determinants of Successful Selective Tracheobronchial Suctioning. N Engl J'Med,,289e1060-1063, 1973. I I f I 01 I; 1 4'
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268 PUBLICATIONS (81) Minh, V.D., Kurihara, N., Friedman, P.J.,, and Moser, K.M.: Reversal of the Pleural PFeaure Gradient During Electrophrenic Stimulation. J1AppI Physiol, 37(4):496-504, 1974. (82) Hougie, C., and'Mosery K.M.: Modern Concepts of Fibrinolysis. Advanced _ Hcematology. Butterworths Publishers, London, England, 1974. (83) Goldzimer, E.L., Konopkar R.G., and Moser, K.M.s Rlversal of! the Perfusion Defect in Experimental Canine Lobar Pneumococcal Pneumonia. J Appl Physiol, 37,85-91, 1974. ARTICLES, Car Unger,, Failure Unger,, and'-fv1c Patient (96) Minh, ' and Ma in Tfion (84) Albertini, R.E., Harrell, J.H., Kurihara, N., and Moser, K.M.: Arterial (97) Moser, Hypoxemia lnduced'by Fiberoptic Btonchoscopy. JAMA 230:1$66-1667; 1974. Antitry (85) Minh, V.D., Friedman, P.J., Kurihara,, N., and;Mosery K.M.: Ipsilatercl (98) Catcnz, Transpulinanary Pressures During Unilateral Electroph'renic Respiration. J'Appl _ in Cocc- Physiol„ 37:505-509, 1974. (86) Mink, V.D., Kurihara, N., Friedman, P'.J., and'Moser, K.M.: Reversal of the PleurallPresure Gradient During Eleetraphrenia Stimulation. J AppllPhysiol, 37: 496-504,,1974'. (87) Catanzaro, A., Spitler, L.,, and Moser, K.M.: Immunotherapy of Coccidiaido- mycosis. J Clin Invest, 54:690-7011, 1974. (99) ( 7 00) Hill, R toryDi 83:523; Hill, R D Istress 21;199- (88) Moser, K.lG1., andShibel, E.M.: Heparin in Endocarditis. JAMA 229:1422, 11974. . (101) Spragg, Platele (89) Kravis, T.C., Shibel, E.M., Brooks, J.D., and'Moser, K.M.: Ihcorporation Int Org ofRadiolabelled Fibrinogen into Venous Thrombi Induced in Dogs. Circulation 49:158-164, 1974. (10Z Bracii, - Lavage (90), Sgroiy V.L., J,nes, G.R.,Ashburny W.L.,and Moser, K.M.c A Simple and' EfficientMethod of Dissalving 133Xe ihto Soline. JI Nuc Med Tech, 2(3)::115-716, (1Minh, ' 1974. Hyperir 40(1) 6 (91)'. Kravis,.T.C.,Brooks., J.D., Ulevitchy. R.J., and Moser, K.M.: Purification of Human MM and:ZZ Alp,ha-l-Antittypsin. Chest, 67:338-340, 1975. (]04) Brach, (9L)I Albertini, R.E., Harrell, J.HL, and Moser, K.M.e Management of Arterial Hypo- xemiaJnduced,6y Fiberoptic Btonchoscopy. Chest,,67:134-136, 1975. Sandweiss, D'.A.,.Hareon, J.C., Gosink, B.B.,.and Moser,.K.M.r Ultrasound' in~Diagnosis, Localization,,and Treatment of.LoculatedPleural Empyema: Ann Iht Med, 82c50~53, 1975. During
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(95) 269 PUBLICAT'IONS Unger, K.M., Shibel, E.M., and Moser, K.M.: Detection of Left Ventricular Failure in,Adult Respiratory Distress Syndrome. Chest,, 67:8-13; 1975. Unger, K.M'., Shaw, D., Karliner, J.S., Crawford, M., OlRourke, R:A., and avloser,, K.M.: Evaluation of Left Ventricular Performanee in Acutely III Patients With Chronic Obstructive Lung Disease. Chest,, 68:125-142y. 1975.. (96) Minh, V.D., Dolan, G.F., Kurih'ara, N., Friedman,,P.J., Kanapka, R'.G.,G and Moser, K.1J1,:, Stability in LokiarVentilotion Distribution During Change in Thoracic Comfigurotion~ J Appi Physiol, 39:462-467, 1975. (97) Moser,. K.M'., and Kravis,.T.C.:.. No Statistical Refuge for the Alpha-I- Antitrypsin Deficient Smoker. JAMA, 231:625-627y 1975. (99) (100) ('101) Cotonzaro, A., Spitlery L.E., and Moser, K_M.: Cellular Immune Response in Coccidioidomycosis.. Immunol,, 15:360-371,.19756 . Hi11, R.N., Spragg,, R.G., Wedel, M.K., and Moser, K.M.:, AdulrRespira- tory Distress Syndrome Associated With ColchincineIntoxlcation.. Ann Int Med, 83:523, 1975. Hiil,, R.N., Shibel, E.M., Sprogg, R.G., and Moser, K.M'.: Adtrlt Respiratory Distress3yndrome: Early Predictors of Mortolity. Trans Amer Soc Artif, Int Otgans, 21,199-204'y 1975. Spragg, R.G., Hill, R.N., Wedel, M.K., Masterson, A., and:M'oser, K.M.: Platelet Kientics in Venovenous Membrane Oxygenation. Tians Amer 5oc ArtifInt Organs, 21:171-176,, 1975. (10Y) BrocHi B.B., Harrell, J.H., and Moser, K.M.: Alveolar Proteinosis: Lober Lavage by FiberopHc Broneh'oseopic Technique. Chest, 69:224r227, 1976. (I 03)., Minh,V.D'.,. Dolan, G.F.,, Konopka, R.G., and Moser, K.M.: Effect of Hyperinflation on Inspirotory Function of the Diaphragm. J Appl'Physiol,, 40(1);67-73, 1976. (I04J Brachi B.B., Yin, F., T!imms, R., and Moser, K.M.: Reduced Inspiratory Effect During Intermittent.Mandatory Venti'Ihtion with PEEP. CriticallCare, 4:142,. 1976. 34-12'1 .0 . - 7'8 - 19
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270 PUBLICATIONS ARTICLES, Continued: ARTOCLES, Contir ' (116), Moser F (105) Moser, K.M.: Ventilation- Brach, B.B., Escano, G.G., Harrelll, J.H., and PerfusionAlterations Induced by Fiberoptic Bronchoscopy: Chest,.69:335-337,. , ofMed: 1976. (117) Lanky, S (106) Spragg, R.G., Hill, R.N., Wedel, M.K., and Moser, KJvta Thrombocyta- penia Induced by Extracorporeal Membrane Oxygenation. Sourcebook of ' Pleural E Membrane Lung Technology and Prolonged ExtracorporeallPerfusion. Warren M. - Zapol, Editor (In Press)',. (118) , Kline, L and Mose Patients % (107), Sgrai, V.L., Brach, B.B., Ashburn, W.L., and'Moser, K.M.: Ligh'fSources as a Means ofReprodueingPatientlPotitioning.. Radiology 123:234-235,. Apri1; (119) Minh, V. acit Ca 1977. p y (120) James W' (108) Moser, K.M.: State of the Art; Pulinonary Embolsim. Am Rev Resp Dis, 115: , 829-852, 1977. 1 Accesory Lesion. <, (109) Kidokoro, Y., Kravis, T.C., Moser, K.M., Taylor, J.C. and Crawford, l'.P.: Relbtionship of Leukocyte Elastase Concentrationlo Hemozygous Antitrypsin- (121) Moser, K Deficient Persons. Am Rev Resp Dis, 115:793:$03, 1977. 134-140, (110 Menn idResolution of a Pulmona 111 Moser Ra S S J K M W Ja (122) Moser, K. ) , , y. p ., . ., . .: mes, . ryEmbolus in Man. Western J af Med; 128:60-64, 1978. Poti ents. ' (123), Sgroi V ll (111) .G., and Brach, B.S., Chao,,R.P., Sgroi, V.L., Mlinli, V.D., Ashburnt W Moser, K.Mso 133Xenon Washout Patter.e During,Diaphrcgmctic Breathing. , . Detection Chest 71:735-739, 1977., ' (124) Bookstein, James W. (112) Brach, B.B., Moser, K.M., Cedar, L., Minteer, M., and Convery, R.: Venous Thrombosis.in Acute Spinal Cord Paralysis. Jof Trauma 17(4):289-292,. , in Hemopt), 1977. (1I13)' Moser, K.M., Brach, B.B., and Dolan, G.F.: Clinically Suspected Deep Venous Thrombosis of the Lower Extremities. J.A.M6A. 237(20)':2195-2198, 1977. (114) Mosery K.M., Kidikoro, Y., Mansh,J., V. Sgroi:, Biologic Ha1f~Live and Orgon Distribution of Radiolabelled Human PiMand PiiZAlpha-I~-Antitrypsinin the Dog. J Lob and Clin Med, 91(2)c214-222; 1978. (115) LeMoine, J.R., Mser, K.M.: Radiolabelled Fibrinogen and Impedance Pletflyemography in the Diagnosis of Deep Venous Thrombosis. Vas. Surg, 11c216-218, 1977.
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Moser, K.M,:, New Diagnostic Tecliniques for TFvombophlebitii. Western J of Med 330:331,, Ocbber 1977. Lonky,'S.A., Catarsaro, A., Moser, K,h1s, and Einsteinj H.: Acute Coccidioidal Pleural Effusion. Am Rev Resp Dis, 114:681,,1977. Kline, L.E., Crawford, M.H., MacDonald, W.J., Schelberf, H., O'Rourke, R., and'Moser, K.M.: Non-Invasive Assessment of Left Ventriculbr Performance in Patients with Chronic Obskuctive Pulmonary Disease. Chest, 72:558-564, 1977. Minh, V.D., Dalant G.F., Brochy B.B., Moser, K.M.: Functional Residual Capacityand Body Position in the Dog. J Appi Phys, 44(2)291-296, 1978. Jbmes, W.S., N1inh, V.D., Minteer, M.A., and Moser, K.M.: Cervical Accessory Respiratory Muscle Function in a Patient with a High Cervical Cord Lesion. Chest, 71I:59-64, 1977. Moser, K.M.c Developing a State Plan For Comprehensive Care of COPO Patients. American Lung Association Bulletin,. February 1978. Sgroi, V.L., fv1^ser, K.M.: Technical Aspects of 1125 Fibrinogen Testing for Detection of Deep Venous Tlirombosis. J Nuc Med Tech, 6(2):65-b8, 1978. (124) Bookstein, J,J., Moser, K.M'., Kalafeo, M.E., Higgins, C.B., Davis, G.B., James,, W.5.: The Role of Bronchial Arteniographyand Theropeatic Embolization in Hemoptysis. Cnest, 72(5):658-d61, 1977.
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272 PUBLICATIONS BOOKS: ABSTRACTS: (1) Rossier, B'uhlman and Wiesinger: Respitation: Physiologic Principles an&Their (1) Calcific Aortitis. Clinical Applications. Edited:and Trams ated' y P.C. Luchsinger and K.M. Moser.. C.V.. Mosby and. Corr-?ony,St. Louis,. Ivlissouri,. 1960. (2) Physiolo (2) Moser, K.ML:Use ocAnficoagulont',and Fibrinolytic Agents. Disease-a-Mbnth,. P.C., h, March, 1960. (3) Mathemr (3) Moser, K.M'.:Th'ercxutic Implications in Fibrinolysis. Controversy in Medicine,. in a Fix, d L l: (4) 135-148, W.B. Saunders Company, Philadelphia, 1966. Moser, K.M'.: Harrison'! Principles of,lnternal Medicine ($ixth Edition), Chapter (4) an uc The Effe 273- Diagnostic Approac tof e Patient with u monary Disease.. MtGrow-Hill Publishers, New York, 1970. (5) Luchsi nc Coagulo (5) Moser, K.M'.:. Harrison's Principlesof Intemal Medicine (Sixth Edition),,. Chapter Plmmin 277: PUlmonaryThromboembolism. McGraw-Hill'Publishers, New York, 1970. (6) Analysis (6) Moser, K.M.: Maximal Voluntary Ventilhtion in Mon: Prediction Formulas and singer, Normal Values. P. 71-72 iniRespiration and Circulation. Edited by Philfp L. Alhmmn Th Ditirner. Federation of Americani Societies for ExperimentallBiology, and Dorothy S (7) erapy ' . Bethesda, Maryland. Moser, Kenneth M. and Stein, Myron, Editors. Pulmonary Thromboembolism. 8) and Lbb, W. E.. Effect oi (8), Yearbook MedicallPublislher, Chicago, Illinois, 1973. Moser, K.M.: Clinical'Application of Ventilation/Perfusion ScintipRotography. Stoker, Textbook of Pulmonary Diseases, Second'Edition. Gerald L. Baum, Editor (9) Effects c . Little, Brown and',Ca., Bostont Moss. 1974. Moser, 2:86, 15. (9) Moser, K.M.: Diagnostic Ptocedures in the Patient of Respiiatory Disease. HarrisonY Textbook of Medicine, Seventh Edition. McGraw-Hill Publishers, (10) Couse ai New York, 1974. (11) and M!a Effect o (70): Moser, K.M.: Pulmonary Thromboembolism.. Harrison's Textbook of Medicine,, d S Seventh Edition. McGraw-Hill Publisher, NtwYo , 1974. tu y. (11) : Management ofiAcute Respiratory. Failure. Harrison's Textbook of Moser K M (12) The Effe . , . . Medicine,.SeventhEdit'ion. McGraw-Hi3lPublisher,NewYork, 1974. Functi or 15 8 66 : , (92), K.lv1., ArcFibaldi, C., Hansen, P., Ellis, B., Beaman, A.JL,, Moser Modtak M. , , , BetterLiving and Breathing: A Manual For Patients.C.V..Mosby and Dunn DL: (13)i Behavia ,. . and'Companyy. St. Louis,NSissouri,. 1975. S.B., N.
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Calcification of the Ascending Aarta: A Study of'its Diagnostic Specificity for Luetic Aortitis. Leonard,,J.J'., and Moser, K./Jt.. Circulation, 1957. Physiologic Definition of Pulmonary Vascular Stattn in AtriallSeptol Defect. Luchsingery P:C., Moser, K.M., and Buhiman, A.. Circulation, 1957.. Math'ematiaal Analysis of the Role of Contact Time in Alveolo-Capillary Oxygen Exchange in a Fixed Pulmonary Resistance System. Moser, K.M., Katr, S, McCormick, G.F.,, and LucWinger, P.C.. Clio. Res., 5:224, 1957. The Effect of Pblmonary Capillary Blood'Flcw Upon Alveola-Capillory Gas Exchange. Luclssinger, P.C., McCormick, G.F., and Moser, K.M.. Clin. Res., 5:118, 1957. Coagulation Changes, Systemic Toxicity and Fibrinolytic Activity Following Intravenous PPasmin (Fibrinolysin): Infiision in Humans. Moser, K.M.. Clin. Res., 6:204,, 1958. Analysis of Factors Influencing Alveoio-Cepillary Oxygen Diffusion inthrLung. Luch- sfnger, P.C., /vloser,,K.M., and Katz, S.. Clin. Res., 6:313y 1958. Therapy ofthe Human Thrombo-Embolic Disorders with Fibrinalysin (Plasmia)'p Clinical and Laboratory Evaluation. Moser,.K.M., Ryan, T.J.,.Sulavik, S.B.,ond DeGroot, W.E.. Circulation, 1958. EffeaYof Oxygen Adrninistration on Various Forrra of Cardiac Disease. Luchsinger, P.C., Stoker, M.C., Leonard, J.JI, Moser, K.M., and Katz, S.. Circulation, 1958. Effects of Induced Hyperpyrexia Upon Pulmonary. Function and Hemodynaimiain Man. Moser, K.M., Perry, R.B., Sulavik, S.Bs,, and Luchsinger, P.C.. The Physiologist, 2:86, 1959: Cause of Dyspnea in Chronic Congestive Heart Failure. Luchsinger, P.C., Ryan, T_J., and Moser, K.N1.. Circulation, 20!731, 1959:• Effeat, of Human Fibrinoiysin(Plasmin)~UponDeep Thrombophlebitis.in Mcn: AControllLd' Study,. Moser, K.M., Hajjar, G.C., and Sulavik, S.B.. Circulation, 20i742, 1959.* The Effects of Induced H'yperpyrexia Upon Pullnonary Hemadynamics cnd'Alveolb-Respirotory Function. Moser, K.M., Lucksinger, P.C., Sulavik, S.B., and Peny„R.B'.. Clin. Res., 8i66,, 1960." Behavior of Pulmonary Emboli in the Dog: Physiologic and Anatomic Studies. Sulavik, S'B., Moser, K.M., and'Luchainger, P.C.. CItn. Res., 8:193; 1960.
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274 PUBLICATdO NS ABSTRACTS, Continued: ABSTRACTS, Continu (29) Cordiopulmonm (14), Diurnal Variation in Piasma Fibrinogen Levels and Euglobulin Activit'y in Normall, Diabetic and Cirrhotic Subjects. Hajjar, G.C., and Moser, K.M.. C1in. Res., 9:21 1961.** Maser,. K.M:,. , (30) Pulmonary Angi (15) Peripheral Arterio-venaus Fibrinogen Levels and Euglobulin Activity at, Rest and Moser, K.M., Exercise. Moser, K.M., and Hajjar,,G.C.. Clin. Res., 9:163, 1961.. (31) ClIn. Res., 14: Potentiation of (i16): Heparin-Fibrinolytie Synergism In Vivo. Hajjpn, G.C., and Moser, K.M.. Clin. Res., 10:26; 1962.** G.C.. Grculb (32) Quantitction o{ (17) d8) If hibition of'Fibrinolytic Activity 1h,Vitro and'In Vivo by Lysine Monohydrachloride. Moser, K.M., and Hcjjar, G.C.. Clin. Res., 10:26, 1962. Plasma Inhibition of 5peciFic Fibrinolytic Substances: Its Variation. Moser K.M'. $cintillttion Cs K.IvI- Clin. I d9), , , and Hbjjaq G.C.. Clin. Res., 11:33, 1963. Importance of Duration of Therapyy in Inducing ThrombolysisIn Viva. Moser, K.M., (33) Correlation ofl, Pulmonary Emb, G.A.. Clin. I and Hajjary G.C.. Clin. Res., 12:34, 1964. (34) Pressure-Flaw-` (20), Results of Steroid Therapy in Patients With Pulmonary HistiocytasisX, Moser, K.M.,, and'Moser~ K. and Reilly, M.J.. Clih. Res., 12:45, 1964. (35) Effects of Hypo (21) RespirctorInduced Apnea. Moser, K.M., and Rhodes, P. G.. Clih. Res., 12:70, 1964.* Fed: Proc., 26 (36) Plasmih-Induce (22) Sources of Error in Oxygen Tension Determination. Rhodes, P.G., and Moser, K.M.. . Fed. Proc 1964.' 23:468 Moser, K.Iv1., ., , 36:11-193, 19E (23) PostHyperventilation Apnea Maser M. Rh'odes P;G and Kwaany P . Fed. K L . . ,. . . , ,. ., . (37) Effect of Acute (24) Proc., 246273, 1965.* K.M Polcrographic Measurement of Blood Oxygen Tension: Sources of Error. Moser and'Mbsery K.i 25) , ., Rhodes, P.G., and Kwaan, P:L.. Clin. Res., 13:51, 1965. Rote Mos.er . K 1v1 . and Rhodes P Effectlof Nebulizedlsoproterenol Upon Cardiac G (38) UK-Plasmin Th~ J., Moser, K., , , . . ., . ,. . . . .. Clin. Res 13:27 1965. (39) Insight Into BIb ., , Via Ventilatior Res., 16:57, 1' (26) Intracardiac Venoarterial Shunting in Pulmonary Emphysema. Bostock, B.A., Westura, E.E., andNaser, K.M.. Cfrculation, 32d11-55, 1965. (40) Acute Hemodyr (27) Scintillation Camera Studies of Lung Blood Flow. Miale, A., Jr., Moser, K.M., and Harsanyi, P:, Landis, G.A.. Clin, Res., 14:105, 1966. (41) Pressure-Flow i (28), Effects of Pre-Medication and Anesthesia Upon Fibrinolytic-Caagulation Behavior. K.M., Harsanl, Hajjar, G.C., and Maser, K.M.. Clin. Res.,, 14:53, 1966.
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Cardiopulmonary Responses to Acute Hypoxia and'Hypercapnia in Aviation Pcrzonnel., Mcser, K.M., Rhodes, P.G., and Westura, B.E.. Fed. Proc., 25:390, 1966'.• Pulmonary,Angiographic-Radiascan Correlation in Patients With Pulmonary Embo{ism, Moser, K.M., Tisi, G.M., Rh'odes„ P.G., Lcndis, G.A., and'Miale, A., Jr.. Clin. Res., 14:105, 1966. Patentiation of UK-Plcsmin Thrombolysis With Heparin. Moser, K.M., and H6jjory G.C.. Circulation, 34:111-176, 1966. Quantitation of Regional Pulmanary$lood Flaw In Vivo by DigitallDcta From the Sciniillatian Camera. Tisi, G.M., Landis'; G.A.,, Miale, A., Jr., and Moser, K.M.. Clih. Res., 15:48, 1967.•• Correlation of Angiographic-Radiophotascan-Anctomic Findings in Experimental Pulmonary Embolism. Moser, K.M., Rius-Garrigo,, J., Hajjar, G.C., and:Lcndis, G.A.. Clin. Res., 15:75, 1967." Pressure-FIow-Volume Profiles of Respirators. Rhodes, P.G., Youngchciyud, P., and Mcaer, K, M:. Clin. Res., 15:48, 1967. Effects of Hypoxemia on Blood Ammonia. Termini, J.E., and Moser, K.M:. Fed. Proc., 26:334, 1967.* Plhsmi.n.lnduced Lysis of'.Moderate and Massive Experimental Pullnonary Emboli.. Mcser, K.M., Rius-Garrigo, J., Haaany,i,, P., and H6jjPr, G.C.. Circulation, 36:11-193, 1967. , Effect of Acute Changes in Po2; Pco2 and pH on Digitalis Toxicity. Tisi, G,M" andlMoser, K.M.. Circulation, 36:11-250;,1967, UK-Plasmin Therapy of Massive Experimentcl Pulmonary Embolism. Rius-Garriga,, J., Moser, K.M., Harsanyi, P., and Hajjar, G.C.. Clin. Res., 16156,, 1968. Insight Into Blood Gas-Spirometric Disparity in Chronic Obstructive Pulmonary Disease Via Ventilation/Perfusion Photoscanning. Shibel, E.M:, and Moser, K.)vl,. Clin. Res., 1657; 1968. Acute Hemodyncmic Consequences of Inferior Vena Cava Ligation. Moser, K.M., Harsanyi'y P., Rius-Gorriga, J., and Guisan, M.. Clin. Res., 16:72, 1968.
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PUBLICATIONS ABSTRACTS, Continued: (42) Diagnostic Value of Combining Ventilation and: Perfusion Photoseans in Pulmonary Embolism. Bronikowski, J:, H6rsanyi, P., and Moser, K.M.. Circulation,,38; VI-48; 1968'. (43), Specificity of Ventilation Plus Perfusion Pfwtosoans in Diagnosis of Pulmonary Embolism. Bronikowski, J., Harsanyi, P., Lanids, G., and'Mosen, K.M. Clin. Res., 17:47, 1969. (4it)i Induction and Reversal of Hypoxic Pulmonary Vasoconstriction. Shibel, E., Harsonyi, P., and Moser, K.lSt. Clin. Res., 17:50', 1969 (45) Effectof Progressive Pulmonary Arterial' Narrowing Upon Pulmonary Vascular Resistance. Guisan, M'., Horsanyi, P., and Moser, K.M. Clin. Res., 17:81i, 1969. (46) Post'rMortem Dissolution Rate of Pulmonary Emboli in the Dog. Guisan, M., Harsonyi,. P., and Moser, K.M. Clln. Res., 18c146, 1970. (47) The Physiologic Profile of Long-Term Autotransplanted Canine Lungs. Tiei, G.M., Trummer,,M.J'., Cuomo, A'.J., Ashburn, W.L., and Moser, K.M. Clin. Res., 18:1!46, 1970. (48) Vascular Reactivity of Long Term Autologously Transplanted Canine Lungs. Tisi, G.M., Trummer, M'.J•. Cuomo,,A.JL, Owry; J.H., Ashburn, W.L. and Moser,. K.M. Fed. Proc. 29:528, 1970.* (49) Composite and RegionallWashouYof 133Xenon Gas from the Lungs: Comparison with Nitrogen Wash'out. Guisan, M., Tisi, G.M., Ash'burn,, W.L. and Moser, K.M. Csin. Res., 28:4$4, 1970. (50) Pre-and Post-Mortem Dissolution Rate of Pulmonary Emboli'in the Dog. Moser, K.M., Guisany M., and Horsanyi~ P. Clin. Res., 28:488, 1970. (51) Differentiotionof Pulmonary Vascular from, Phrenchymal Diseases by. Ventilation/ Perfusion Scintiphotography. Moser, K.M., Guisan, M., and Ashbum, W.L. Ann. oflnt. Med'., 72:808, 1970. (52) The Effect oflnspited CO2 on Hypoxemia Due to Regional Ventilation-PerFusiom Inequality. Reid, D., Tisi; G.M., Minh, V.D:, and'MOser, K.M. Clin. Res., 19:147, 1971. ** (53) Diophragmatic Dtsfribution of Phrenic Roots in the Dog. Minh, V'.D., and'Moser, K.M. Clin. Res., 19:146, 1971. (57) A3STRACTS, Cont (54) Threshold Di phrenic ResF (55) Threshold Dii phrenic Resp System and I Jr. Plenum (56)i Ventilation/1 for Pulmonar Ann. IM~. M Dimensional Tisi,, G.M., 243, 1972.' (58) Regionai Ver Pathophysiol, Moser, K.M (59) I ; Radio-labell Kravis, T.C. 105;990, 19,- (60) Cuff-Inducec C.R., Dunnj (61), Diaphragrnati Minh, V.D. (62) Change in P1 V.D. and'Mi Coccidioidon Maaer,, K.M'. Analysis of R 133Xenon. 1 21 i: 668, 197 Defective Ce Moser, K.M.
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Threshold Distributions of Phrenic Nerve Motor Fibers: A Factor in Smooth Electra- phrenic Respiration. Minh, V.D., andlMoser, K.M. Clin. Res., 19:192, 1971. Threshold Distributions of Phrenic Nerve Motor Fibers:, A,Factor in Smooth Electra- phrenic Respiration. Minh, V.D., and'Maser, K.M. p. 109, in The Nervous System and'Electric Currents. Edited by Norrnan L. Wulfsohn and Antkony Sances, Jr. Plenum Press, New York. 1971. - (56) Ventilation/Perfusion Scintiphotography in the Pre-Operative Evaluation of Patients for Pulmonary Resection. Cuomo, A.JL, Oury, J., Reid, D., and Moser, K.M. Ann. lnt. Med., 74:8401 1971. (57) Dimensional Response of Central and PeripherallAiiv+ays to Trarspulmonary Pressure. Tisi, G.M., Minh, V.D., Friedman, P.J., and Moser, K.M. Clin. Res., 20: 243, 1972 " - (58) Regional Ventilation/Perfusion Profiles oflthe Pink Puffer and Blue Bloater: A Patflophysiologic Basis for Their Divergent Pattern of' Breathing. Keens, Ti.G., Moser, K.M., ond Tisi, G.M. Clin. Res., 20579,, 19772L• (59)' Radio-lbbelled Fibrinogen as a Method for Studying Experimental Venous Thrombi. Kravis, T.C., Freeman, 5., Baooks, J.D. and Moser, K.M, Am. Rev. Resp. Dis., 105:9901,1972. (60) Cuff-Induced Ttacheal Injury,: Influence of Ihttacuff' Pressure and Hypotension. Dunn, C.R:, Dunn, D.L. and lvloser, K.M. Am. Rev. Resp. Dis., 105;1001-1002, 1972. (61) Diaphrogmatic Ton a: A Third Factor in Determining the Pleural Pressure Gradient. , Minh, V.D. and'Moser, K'.M. Ciin. Res., 21: 278, 1973.•• , (62) C}iange in Pleural Pressure Gradient Developed'by Lobectomy_ Dolon, G,F., Mink, V.D. and Moser, K.Iv1. Clin. Res., 21: 277, 1973.** (63) Coccidioidomycosis: Stijdy af Cellular Ilnmunity: Catanzaro, A., Spitler,, L. and' A>loser, K.M. Clin. Res., 21: 214, 19Td'. (64) Analysis of'Regional Dynomia During the Forced Vital Capacity (FVC) Maneuver Wsing 133Xenon. Minh, V.D., Overton, T.R., Sproule, B.J. and Moser, K.M. Clin. Res.,. 21: 668;, 1973. (65) Defective Cellular Immunity in Patients of Coccidioidomycasis. Catar¢aro, A. and Moser, K.M. Am. Rev. Resp. Dis., 107: 1084, 1973.
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278 PUBLICATIONS' ABST!RACTS„ Continued: (66) Gas Exchange Abnormalities Induced During,Filiereptic Bronchoscopy: Herrelll, Ji.H., A'Ibertini., R.E., Kurihara; N., and Moser, K.M. Am. Rev. Resp, Dis., 107: 1091, 1973. (57) (68) Detection of Left Ventticular Failuro-in Patients With Acute Respiratory Distress Sy,ndrome. Unger, K.M., Shibel, E.M., and Moser, K.M. Am. Rev. Resp. Dis., 107: 1111, 1973. 1251-Fibrinogen in the Diagnosis oflDeep Venous Thrombosis. Moser, K.M'., G.F. Dolan, R.E. Albertini, and A. Catanzaro. Clin. Res., 22: 119A, 1974.*' (69) Occurrence and Reversibility of Pulmonary Perfusion Alterations in Experimental Pneumo- coccal Pneumonia. Goldzimer, E.L., R.G. Konopkat and K.M. Moser. Clin. Res., 22; 132A, 1974.*' (70). Lob'ar Interdependency in Ventilation Distribution. Dolbnt G,F., V.D. Minh, N. Kutihora,. P.J. Friedman, and K.M. Moser. Clin. Res., 22: 199A, 1974.** (71), Effect of Thoracic Configuration on Airway Morphometry. Kurihara, NL, P.J. Friedman, V.D. Minh, and K.M6 Mlser. Clin. Res., 22h 201A, 1974. ** (T1) Lobar Ihterdependence in Ventilation Distribution. Minh, V.D., G.F. Dalan, N. Kurihara, P.J. Friedman, and K.M. Moser. C1in. Res., 22! 510A, 1974. * (73) Differentiation Between Pneumonia and'Pulmonary hn6oiism by Perfusion Scintiphotograp6y: A,New Approach. Mhser, K.M., E.L. Goldzimer, ord''W.L. Sperling, Am. Rev. Resp. Dis., 109:696t 1974 ' (74) Transfer Foctor?herapy in Coccidioidomycosis. Catanzaro, A., L.E. Spitler, H. Einsteinj and K.M. Moser. Am. Rev. Resp. Dis., 109: 724, 1974. * (75) (76) (n) Reversal of Pleural Pressure Gradient by Electrophrenic Stimulation. Minh, V.D., N. Kurihara, P.J. Friedman, and K.M'. Moser. Fed. Proc., 33:440, 1974.* Effect of Hyperinflation omDiaphragmatie Function. Dolan,, G.F., R.G. Konopka,. P.J. Friedman, V.D. Minh, and K.M.,Moser. Clin. Res., 23: 1116Ay 1975." Resting Lung Volume and Pleural Pressure (Ppl) in Immersion. Lihaweaver, P.G., G.F.,. Dolan,,R.G.Konopka, D.W..Hauer,.V.D.lvSinh,.and'K.M..Moser. Clin. Res.,.23:. 117A, 1975, " ABSTRACTS, (. (79) Unger, R.: Le Citauld (60) MacDa Echoca Clin. I (81) Minh, During (82), Brach,. Spinal (8.3), Shepan on Gas 113:16' (84) Kline, E(eatia Rev. Rf (85), Brach, Dlaphn Am. Re (66) Brach, Extensi (87) 1vlinh, ' on FIoH (88) Francoa of Vent Lavage (89) LeMoin Compli, (90) Moser,. (78) CephalbcaudalLExpansion~ofRegional'Lung Units During ElecttophrenicRespiration. Minlh,, and Per V.D'., N. Kurihara, G.F. Dolan, P.J. Friedman, and K.M. Moser. Fed. Proc., 34: 430, Chest, 1975. ' (91). Sander L. Al LeftlPc
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Unger, K.M.,Shaw, D.,, Karliner, J., Crawford, M., Moser, K.ld1.,, and O'Rourke, R.: Left Ventriculbn PerForrnance in Potients with Chronic Obstructive Lung Disease. Citculation, 50:T4y 1974 (supp)'„ MacDonald,, W:, Jr., Kline, L., Crawford, M.HI., Moser, K., and O'Rourke, R.: Echocardiographic Assessment of LeftVentricular Function in Chronic Lung Disease. Clin, Res., 24':B6A, 1976c Minh, V.D., Moser, K.M., Dolan, G.F., and'Btoch, B.B.: Regional Lung Stiffening During ChestlWall Distortion. Clin. Res., 24:160A, 1976. Brnch, B., LeMcine, J., Dolan, G., and'Mosery K.M.: Venous Thrombosis in Acute Spinal Paralysis. Am Rev Resp Dis, 113:142; 1976. Shepard, JLW., Jr., Hauer, D., and Moser, K.M'.: Effects of Isoproterenol Infusion on,Gm Exchange and Distribution of Perfusion in EmboLized Dog$.. Am.Rev. Resp. Dis.,. 113:167, 1976. Kline, L., MacDonald, W., Crawford, M., et aL: Echocaniiographic and Radionuclide Ejection Fraction Assessment of LeftlVentricular Function in Chronic Lung Disease. Am. Rev. Resp. Dis. 113:177, 1976. Broch,, B., Chao, R., Sgroi V„ Ashbum, W., and Moser, K.M.: Effects of Diaphragmatic Breathing on 533Xenon Washout Pattems in Normalland'COPD Pbtienti. Am. Rev. Resp. Dis., 113:215, 1976. Brach, B., Minflt V.D., Konopka, R.,, and Moser, K.M.: Chronic Overinflation After Extensive Lung Resection. Am. Rev. Resp. Dis., 113:249, 1976. Mink, V.D., Lanky, S., Konopko, R., and Moser, K.M.: EffectoF Chestwall'l on FIbw-Volume Curve. Am. Rev. Resp. Dis.,, 113:255, 1976. Franeoz, R'.A., Konopka, R., Sgroi, V., 8mch, B.B., and'Moser, K.M.: Evaluation oflVentilatian and Perfusion Changes inAnesthetizedDogs Follbwing Saline.LoFioir Lavage. Chest, 70:427, 1976'. LeMoine, J.R.,.Brach, B., Convery,, R..,and Moser, K.M.: ThromboemFiolic Complications Following Hip Surgery. Chest, 72!404,. 1977. Moser., K.M., Kidikoro,.Y., and Landbn, C.: Topographic Differences in Ventilation and Perfusion Distribution, in Patients with ZZ and MM Alpha-l-Antitrypsin Phenotypes. Chest, 72:408,,1977. Sanders,.B.S,,.Shepard, J.W'.,.Jr.,,Job'e,.A., Miyai~ K., Moser, K., and Gluck, L.: Alveolar CO2 Tension as a Mediatov of Lamellar Body Release in Experimental Left Pulmonary Artery Occlusion. Chest, 72:411y 1977.
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280 PUBLICATIONS ABSTRACTSy (Continued)t (92) (93) Spmgg, R:G., Loomis,, W.H., and Moser, K.M.: Prolonged Extracorporeal Bypass Without Thrombocytopenia6 Chest, 72:413, 1977. Shepard, J.W., Hauen, D.HL, and Moser, K.M.:' Mechanisms of Hypoxemia During Pulmonary Vascular Occlusion and Following Reperfusion. Am. Rev. Resp. Dis., 115:161, 1977. (94) Bmch, B., Sgroi, V., and Moser, K.: Postural Changes imPullnonary Blood Flow as an Indieator of Pulmonary Hypertension. Am. Rev. Resp. Dis., 115:308, 1977. (95) LeMoine, R., and Moser,, K.: Does A'Safe"' Form of Lawer Extremity Deep Venous Thrombosis Exist? Clin. Res., 26:136A, 1978. (96) Kalafer, M.E., Catanzaroo ,A., Harrell, J.H., Bums, D.M., Francozy R.A., and Moser, K.M.: Human Airway Lymphocyte Response to PHA and Antigen. CI6n. Res.,. 26:122A,,1978. (97) Francoz, R.A., Bums, D.M., Kalafer, M.E., Han•ell, J.H., Sgroi,, V.L., Catdnzaro, A., and'Moser, K_M.: The Effects of Saline Labor Lavage in Normal Human Adults. Clin. Res., 26e13,5.4, 1978. DIVISIO NAL AR Marke~ FI Braschj R 2. Structure Hathway, 139d,1401 3. The Tubes Termini, 41. A CompuU Sehmeehe DIVISIONAL AB° 1. Structure !c%` 2. Hathway, IhVivo Bn Cleavage 654'y 1972 2. Identifica ' Presented'atlNationol Meeting 3. Kravis, T Dimension " Presented at Sectional!Meeting pulmonary Dis., 1Q5
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DIVISIONAL ARTICLES WITHOUT DR. /v1OSER'S NAME Markeo Hypercapnia Secondary to Severe Nletabalic AIkalosis. Lifchitz, M.D., Braseh„R., Cuomo, A.J. and Menn, S.J'. Ann. Int. Med., 77: 405-409, 1972. Structure and In Vivo Behavior of' Hbman Fibrinogen Fragment D1 . Catanzoro, A. Hathway, G., Skathern, J. and Edgingtan, T. Proc. Soc. Exp. Biol. Med., 139:1401-1406, 1972. 3. The Tuberculin Test. Effects of Storage and Method of Delivery on Reaction Size. Termini, J.E. and:Wijsmuller,, G. Am. Rev. Resp. Dis. (Accepted for publication). 4. A Computer Program to Assist Acute Respiratory Care. Menn, S.J., Barnett, G.O., Sclumechel, D., Owens, W.,and Pontbppidan, HL JAMA (Accepted for publication). DIVISIONAL ABSTRACTS WITHOUT DR. MOSER'S NAME 1. Structure and In Vivo Behavior of Human Fibrinogen Fragment Dl. Catanzaro, A., Hathwcy„ G., Strathern, J.,and'Edgington, T. Presented at FASEB, Chicago, 4/71. 2. In Vivo Behavior of TenninallCleavage Products of Fibrinogen Compared with Terminal Cleavage Products of Fibrin. Catanzaro, A. and Edgington, T.S. Fed. Proc., 31: 654, 1972. - 2. Identification and Characterization of Antibody in a Four Hour Rabbit PCA Reaction. Kravis, T.C. and:Zvoifter, N.JL Fed'. Proc., 31e 757, 1972. 3. Dimensional Response oflCentral and PeripherallAine•ays to Lung Volume and Trans- pulmanarq Pressure. Tisi, G.M., Minh, V.D. and Friedman, P.J. Am, Rev. Resp. Dis., 105: 101i4-1015, 1972.
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282 CDHBiCULUC VITiAE Theodor D. Sterling EDUCATQOH A.B. (CUtf LAUDE)i, 1949, e.A., 1952, University of Chicago; Ph.D. 1955, Tulane University. PROFESSIONAL AFFILIATIONS Present: Professor, The Faculty of Interdisciplinary,Studies and Department of Computing Science, Simon Fraser Dniversity. Previous: Visiting, Professor, Department of statistics, Princeton Qniversity,, (78). Chairman, Department of Computing Science, Simon Fraser University„ (72-77). Professor in the Department of Applied dathematics and Computer Science, Gashington University, St. Louis, Missouri (66.72). Also Joint appointment as Professor in the Department of Sociology (66-68), and Visiting Professor in Computers and Humanities, Hebrew Union College, Cincinnati', Ohio (fi8-7D). Professor of Biostatistics and Director of the Computing Centre, college of tledicine, University of Cincinnati, Cincinnati, Ohio (58-66):. Previousl'y instructed in the Department of Statistics, tlichigan, State University and Department of nathematics, University of Alabama. PROFESSIONAL ACTIVITIES Present: President of the Computer Science Association of Canada (75- ); Chairman Ombudsman Cemmittee, Canadian Infbrmation Processing Society (73- );; Chairman, CIPS Special Interest Groups, Humanization cf Information Systems (73, ), Chairman, SdGCAS Committee of Information and Public Policy (72- ). Previous: President of Biological Information Processing Organization (64-65); President of Missouri Chapter, American Association of Workers for the Blind (70-72); Member of the Panel for Biology, Management, and Social Sciences of the Mathematics Association of Ameriea (62-67); Chairman, Committee on ProfessionaL Activities of the Blind of the Association for Computing Eachinery (63-71); Chairman, Ad Hoc Committee on Accreditation, Association for Computing Cachinery (66-67); Committee on Radiation Dosimetry, American Association of Physicists in medicine (66-69)i; National Lecturer for Association for Computing Machinery (72"3, 75-6)~. EDITORIAL ACTIVITIES: lssociate Editor - Canadian Journal of Statistics (73-78), Editorial Board - International Journal of Biomedical Computing (69- ), Computers, 6 AppLied Mathematics (73- ), Humanist in Canada (73- ). GOVER6EENT Ab ConsuLt' . Commissi Eesourcf Also se, (fli~nnesc. Associa! Control. PROFESSIONAL Can. Ii Cacbines Amer. Assoc. Epsilon;
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283 hnd 8), "on "cs ne, sly a te a. ada ion est an, ;ing can inel acs on for on 7) ' I of tiori GONERHEENT AND: OTHER SERVICES: Consultant/adviser: (in Canada) - Environaent Canada, The Royal' Commission (B.C.); (in U.S.)i - NIH, PP95, EPA, FTC, SRA°;Naturali Resource Board (Slisconsin); (in Kutiait) - Hinistry'y of Healith.Al~so served asadv:ser to Environcen~tal Defense Fund, GECCA (Hinnesota),. Citizens Against Tczic Sprays (Oregon), Consumers Association of Canada, Society for Professional and Environmental Control. PROFESSIONAL AND HOBORABYSOCIETIES,. RONORS, AWARDS Can. Inf. Proc. Soc.; Can. Comp. Sci. Assoc.; Assoc. Comp. tlacbinery; Amer. Math. Assoc.; Math. Soc.; Inst. tlath. Stat.; Amer. Stat. Assoc.; Biometric Soc.; N.Y. Acad. Sci.; Amer. Assoc. Phys. tled.; Assoc. Ras Opthamaloqy; Sigma Xi; Pi Cu Epsilon; Morrison Cressy Award in Natural Science. ( k I u .l i R Ka ®
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284 BIBLIOGSAPHY Theodor D. Sterling Books System I 11 Guide to PL/1. Holt, Rinehart and Winston, February, 1969. the ACM. second edition - 1976. Essentials of PL/1. Holt, Rinehart and Winston, January, 1973. Frequenc J. of Cc Visual Prosthesis - The Interdisciplinary Dialogue. (Editor), Academic Press, llarch, 19711. Computei Society Computing and Computer Science vith PL/1'. tlacmililan~ January, Computet Pe s ]i 1970. r ona Coaputing and Computer Science with Fortran IV. eacmillany January, 1970. Smokinq Archiv e: Introduction to Statistical Data Processing. Prentice-Hall, Frequenc Cha e June 1968. rg Advances in Biomedical Computing Applications (Editor), annals Compute3 of The New York Acade®y of Science, Vol 128, 1966. Does So Health : Computers and the Life Sciences. CoLumbia Press, December, l 1965. low i Fo n preparation: People are Trouble: The Human Side of a Computerized Society. Columbia University Press, 1979. Computers and Programminq - An Introduction. Holt, Rinehart and iiinston, 1980. A ustr alli Programc A. G. ac Technol< Humanizi and Ken1 Carcel I
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1978' System Errors and Their I~®pact on End Users. Coamunications of the ACM. (In Press) Frequency and Types of Ccmputer Related Errors Among the Public, J. of Consumer'Research. (In Press) Computers, danagement Information Systems, and Democracy. Society (In Press)i. Computers in Developing Nations:, A Cautionary Tale. J. Personal Computing (In Press). Smokinq Patterns by Occupation, Industry, Sex, and Race. Archives of Envircnmental Health. October. Frequency of Coaputer Related Errors Among Holders of Credit, Charge or Bank Accounts: Report of a Study of the Vancouver Computer Ombudsman. CI,PS neviev, 2/5: 19. Does Smoking Xill Workers on Working Xiil Smokers, Int. J. Health Services, 8/3: 437-452. Follow up: New Evidence Concerning Smoking and Health, tlad. J. Australia, 65: 38u-387. Programming in High Level Languages in delzsr, J., Holzaas, A.G. aad Kent, A. Encyclopedia of Computer Science and Technology, riarcel Dekker. Humanizing, Informa ti'on Systeas in Belzer, .T. , Holiz9an, A. G. and Kent, A. EncycLopedia of Computer Science and Technologg, tlarcel Dekker. 34-121 0 - 78 - 19
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286 3 1977 Natural Language Compilers and Interpreters in Radiation Treatment P1'anning. Proc. 6th Iat. Confce. on Use of Computers in Radiation Therapy, Goettingen. Computers in Developing Nations: d Cautionary Ta1le. Communications of the ACM. December, 20/12: 971-972. Per Evidence Concerning Smoking and R'ealth. ried'ical Journal of Australia, October, 2/538-542. Fold, Spindle and eutilate. Bumanist in Canada, tlarch. 40/1b-20. Exposure to Pollutants in Enclosed "Living" Spaces. Environmental Research, February,, Vol 13/1. 2,4,5-T .... Teratogenic Embroyotoxic, Fetoqenic, lfutogenic, Acres U.S.A., 7/7. 1976 The 8uman (or the Inhuman) Side of eanagement Information .Systems. Datamation. December. Smoking Characteristics by Type of Employment. J. Occup. Eedicine, November, VoY 18(11): 743-754. Do We Need & Computer Ombudsman? Canadian Datasystems, August, 62- 64',. Programming, 1127-1156, Ralston, A. and Heek, C.L. (Editors), Encyclopedia of Cosputer Science, Petroceili-Ch'arter, New York. , Single-Track Universal Curriculum for Computing Science. IHFOR, February, Vol 14:1, 40-52. c Can Ag Herbici 2- 7. Additio Bearing Journal Relatio the 0. the 197 Humani z: Their Ii A Critic the Cal Septemb( A Critic Fertilit Lung Car Etiologi Essociai senior z Rel~atioa the D.5 Ch ron i c author.) Guidelin Repcrt November Vol 10 (
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287 tlan Against Himself - Biological Dangers from the Use of Herbicides. Humanist in Canada, February, Number 3(Pol IX), 2-7. Additional Comments on the Critical Assessment of the Evidence Bearing on Smoking as the Cause of Lung Cancer. American Journal of Public Health. February, Vol 66:2, pp 161-164. Relation of Place of Birth anditligration in Cancer tlortality in the U.S. - A Study of Ohio Residents (1959-1967), reprinted in the 1976 Year Book of Cancer. r<< I 9 1975 Rumanizing,Computerized Inforaation Systems: Guidelines and Their Implications. Science, December, Vol 190: 1168-1172'. !" A Critical Reassessment of the Evidence Bearing on Smoking as the Cause of Lung Cancer. American Journal of Public Health. September, Vol 65(9): 939-953. A Critical Review of Reports on the Effect of Smoking on Sex and Fertility. Journal of Sex Research. August, Vol 11(3) 201-217. Lung Cancer Among,Black and White Migrants In the U.S. - Etiological Considerations. Journal of the National Hedical Association, March, Vol 67(2): 106-111, 102. (T.F. Gancuso, senior author.) 1974 Relation of Place of Birth and Migration in Cancer nortality in the U.S. - A Study of Ohio Residents (1959-1967):. Journal of Chroni~c Diseases. Vol 27: 459-474. (T. F. Mancuso, senior author.) Guidelines for Humanizing Computerized Information Systems: A Repcrt from Stacley House. Communications of the ACe. i November, Vol 17 (11): 609-613. (Reprinted in AEDS Journal, ; Vol 10 (1) , Fall 1976: 1-1 0. r a 6 ® ® n
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288 5 Teaching Simulators of Ideal Teaching Machines. SIGSCE Bulletin, kCM. June, Vol 6(2): 45-56. A Proposal for a New Curriculum Approach. University Affairs. Simon Fraser University, Burnaby, B.C. tlay, pp. 6-7. Difficulti Effects o Ideal Teaching Machines -- s Solution to the Pedagogic Language. American A communications of the ACM. April, Vol 16: 207-208. 1972. The Use of an Informaticn System to "Humanize" Procedures in a• A Versati Rehabilitation Hospital. International Journal of Bio-Medical: Computatio Computing. Vol 5: 51-57. Vol 2: 17 Information for Publ~ic Policy. Computers & Society. Vol 5(2): Fitting tb 2. (Invited editori'al). Technical Internatic The Simon Fraser One-Track Universal Curriculum for computing Science. SIGSCE Bulletin, ACe. February, Vol 6(1): 28-32. The Incide to the Eti Bealth. I 1973 The Statistician vis-a-vis issues of Public Health. The American Statistician. December, Vol 27(5): 212-217. -- Eztending the General Field Equation to fit the Dose A Critica: Distributions of a Variety of Therapy Units. British Journal of Lung Canc. Radioloqy,. Vol 46: 983-990. (J. Sieinkam, senior author.) American on Smokin, Air Pollution and Smoking_ Environment. Vol 15(6): 3-5, 25-26. Dynamic Display of Radiotherapy Plans Using Computer-Produced Films. Radiology,. June, Vol 107: 689-691. Humanists and the Computer Community. Humanist in Canada. Vol 25: 2+-6. Computing and the Humanization of Medicine. International Journal of Biomedical Computing. Editorial, July, Vol 4(3). 159. Difficult 2,4,5,-T Qol, 174: Some Thou (proceedi Badiother Glicksman Special B Radiology. Three-Dio Films. C
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1972 Difficulties of eeasuring the Effects of Air Pollution vs the Effects of Smoking. Presented at the 139th Meeting of the American Association for the Advancement of Science, December 1972. A Versatile System for Three-Dimensional Radiation Dose Computation and Cisplay, RTP. Computer Programs in Biomedicine. Vol 2: 178-192. (J. iteinkam, senior author.) Fitting the General Field Equation to the Siemens Gammatron 3. Technical' Report on Research Agreement N'o. 1D51/CF for the International Atcmic Energy Agency, Di~enna, Austri~a. The Incidence of Lung Cancer in the U.S. Since 1955 in Relation to the Etiology of the Disease. American Journal of Public Health. February: 152-158. ,'. 1971 A Critical Assessment of the Evidence on the Ciqarette smoking - Lung Cancer Relationship. Presented at the 138th lSeating of the American Association~for the Advancement of Science, Symposium on Smoking and Health Nor. Philadelphia, December, 1971. Difficulty of Evaluating the Toxicity and Teratogenicity of 2,4,9,-T from Ezisting Animal Ezperiments. Science. December, Vol 174: 1358-1359. Some Thoughts on Treatment Strategy. Computers in Radiotherapy (proceedings of the 4th International Conference on Computers in Radiotherapy, Glasgow, September 1970). Edited by A. S. Glicksman, tl. Cohen, and J. R. Cunningha.. Published as Radiology, London. Three-Dimensional Treatment Plan Display on Computer-Produced Films. Computers in Radiology, pp. 12-14. Speci~al Report No. 5 (1971) by the British Institute of
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290 7 A Reviev of the Claia that Excess Corbidity and Disabiliity Can Be ascr+-bed' to Snokinq,. Journal of the American Statistical Association. Vol 66(334): 251-257. a Critical Heassessaent of the Evidence Bearing on Smoking as the Cause of Lung Cancer. Special Report on the Washington IIniversitp Project on the Review of Crucial Data Bearing,or, the Saoking! and Health Issue, St. Louis. Robot Data Screening, An Intelligent (?) Data Search Technigne. AGARD Conference Proce4dings No. 94 on Artificiali Inteiligence, 2-1-2-8, Technical Editinq and Reproduction Limited, London. Coament on Saoking Dogs. Letter to the Editor. Archives of EnvironaentaI Health, vol. 22: 631-632. 1970 A ut eul Aca A C Jou Rob in Com rtea Arc Problems in Determining if a Commonly-Osed Herbicide (2,4,5-T) Has an Effect on Hu®an Health. Proceedings of the Sixth Berkeley Syc+posiua on tlathematical Statistics and Probability, Coi Beld at the Statistical Laboratory, University of California. Ro:' . University of California Press, pp.479-49u:. Ago Experience with a°Oniversal" Introductory Course in Computer oP' Science. Pnoceedings of SI,GCSE Technical, Symposium oa Acadeaic Ro1: Education in Computer Science, November 16, 1i970. Houston, Ag• Texas. SIGCSE Bulletin, Vol 2(3), Association for Coaputing Gachinery, New York. Di Co Robot Data Screening,, An Automatic Search Technique. Ce Bio-Hedicall Computing. Vol' 1: 61-74, (From the Broceedings of In the Conference on Statistical Computation, University of >_ Wisconsin, April, 1969.) Report on Progress in the Develcpment of Visual Prosthesis. The Hew outlook for the Blind. February, Vol 64: 41-45. Au Eg Vc 40 Oa As
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291 8 1969 Automatic Data Screening: A Practical Solution to the Hultivariate Problem in Clinical Data. Annals of the New York ,cademy of Sciences. Vol 1611: 632-640. A Comment on "Air Pollution -- The Industrial Viewpoint". Journal of Occupational tfedicine. July, Vol 11: 381!-383. Robot Data Screening -- A Ubiquitous Automatic search Technique, in Hilton, C. R. and Nelder, J. A. (Ed.), Statistical Co®putationy Academie Press, New York. pp. 31!9-333. Measuring the Effect of Air Pollution on Urban Horb3dity. Archives of Environmental Health. April, Vol 18: 485-494. 1968 ~' Computer Interface, Input riethods, and Presentation of Results. Role o= Computers in Rad_otherapy, International Atomic Energy Agency, Vienna. Paper No. 15, pp. 135-141. Optiui2ation as a Joint Result of Plannir.g and' Iaplementation. Rolle of Computers in Radiotherapy, Znternational Atomic Energy Agency, Vienna. pp. 163-167. Display Devices for Computer Translated Braille. Proceedings Conference on New Processes for Braille Hanufacture, 1968, Center for Sensory Aids Evaluation and Development, Hassachusets Institute of Technology. February, pp. 14-20. 1967 Automation of Radiation Treatment Planning, VI: A General~ Field Equation to Calculate Percent Depth Dose in the Irradiated Voliume of a Cobalt 60 Beam. British Journal of Radiology. Vol 40: 463-468. Urban Hospital eorbidity and Air Poll~ution: Second Report. Archives of Environmental Health. Vol' 15: 362-374. i
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292 9 A New Direction in Rehabilitation Through Advanced Instrumentation andi Computation. Journal of the American Medical Association. Vol 200(7): 625-629. The Use of Computers in Therapeutic Radiology, Summary Report of an International Conference held in Caabridge, England, June 1966 (Editor). British Institute of Radiology, London. Pinal, Narrative Report, Training of the Blind for Professional Computer Work. Department of Realth, Education, and Welfare, RD-1485-5-67-C2'. 1966 Robot Data Screening- A Solution to Multivariate Type Problems in the Biological .and SociaL Sciences. Cooaunicatons of the ACM. Vol 9(7): 529-532. A Biologica11y-0riented Computer Language. Annals of the Nev York Academy of Sciences. Vol 128(3): 755-765. (S. V. Poll~ack, senior editor.), Cancer Therapy - Computation and Visualization of Dose Distributions in External Beam Therapy. Journal of Chronic Diseases. 9o1 19: 523-539. Use of the Computer to Teach Introductory Statistics. Communications of the ACM. Vol 9: 274!-27b. Computers: No Longer a Big Bargain for Uneducated Users. Computers author.) and Automation. Vol 15: 1-4. (S.4. Pollack, senior The Selection, Training, and Placement of Blind Computer Programmers. Report of the Association for Computing Machinery.. Is Medical Diagnosis a General Computer Problem? Journal of the American eedica 1 Association. Vol 198(3): 281-286 Befogging the Issue: California has discovered that laws can't control auto exhaust fumes. Barron's, May 2, pp.5, 14-15. Qrbao Mc Environa The BLiL 7 (1)': i Role of York Aca The Roli Annual Yashinq; Automat Proceed Sensory Institu Automat visuali' R adio lc Robot Epidem: Seience The Ro] annual B. Go4 Spring, Comput< (Ed. ) i, York, ' Tovard Resear Procee
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293 10 Urban lforbidity and Air PolIuti~on: A First Report. Archives of Environmental Bealth. Vol 13: 158-170. _. ii The Blindias Computer Progsammers. Rehabilitation Record. Vol 7(1): 7-10. Role of Statistics in the World of Computers. Annals of the Nev York Academy of Science. Vol 128(3): 1108-1115. The Role of the Blind in Data Processing. Presented at Third Annnal Conference on Computer Personnel Research Group, heldi at Washington University, 1965. Reprinted in Computers and Automation. Vol 15: 24-27. Proceedings on the Braille Research and Develcpment Conference, Sensory ]lids, Evaluation and Development. tlassachusetts Institute of Technology, November, 1966. 1965 sutomation of' Radiation Treatment Planning, V: Calculation and Visual:isation of the Total Treatment Volume. British Journal of Radiology. Vol 38: 906-913. Robot Data Processing Techniques for Huitivariate Epidemiological Predictions. Annals of the New York Acadeny of Science. Vol 126(2): 779-794. The Role of the Blindi in Data Processingw Procedures of Third Annual Computer Personnel Research Conference, June 1965. (n. B. Gotterer, ed.) Computers in Personnel Research Group, Silver Spring, ed.; pp. 31-39. Computation of Radiation Dosages, in 5t'acy, R. and Wasmaay B., (Ed.), Computers in Biomedicali Research. Academic Press, New York, Vol 1 (Chapter 18). Tovard an Undergraduate llathematics Program for Future Researchers in the Fields of Biology and fledicine. Federation Proceedings. Vol 24(1): 5-9. - ' I
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294 11 Careers for the Bl~ind in Electronic ' Data Processing. `FD Electronic Data Processing, occupational Outlook Quarterly. `1 Vol 9 ( 1) : 1-4. Do Hal? -e-; EmpLoyment Potential for the Blind in Computer Related Fields. '"s The international Journal for Education of the Blind. October, Radiatia II.S. Di pp. 1-5. - „ MEDCOMP, ~ Univers The B1!ind in EDP. ACM Committee on Professional Activities of the Blind. Boron, i : 4 Archi~ve. ~ senior + 1964 Potenti Health. Design and operation of a Bedical~ Computing Center. Annals of ± Carcino the New York Academy o Saengar, senior author). f Science. Vol 115(2): 591-599. (E. Reviey. senior Planning RadiationiTreatment on the Computer. Annals of the New Automat York Academy of Science. Vol 115(2): 976-997. System Professional Computer Work for the Blind. Communications of the ,i Distrib ACM. Yol 7(4): 228-231. -ii : 9 Intrave 6 of Acut Computer Qork as a Profession for the Blind. Journal of senior Rehabilitation. Vol 30: 20-21. . oa ,. f j Automat Epidemiology of Disease Associated with Lead. Archives 333 8 ' of i NcnrCoa -34 . Environment a1 Health. Vol 8: . Radiolo dT Mathematical Analysis of Lead Burdens. Archives of .d Environmental Health. Vol 8: 44!-51. ,3 'qt ; Automation of Radiaticn Treatment Planning, IV: Derivation of a Robot Conferc. Hedicin 299-31'. Mathematical Expression for the Per Cent Depth Dose Surface of '1 Cobalt 60 Beass and Visualisation of tlultiple Field Dose Distributions. British Journal of Radiology. Vol 37(439): Robot I on Dat 544-550. York, 1 . zr Locatinq Placenta Praevia. Procedures of the Rochester Conference on Data Acquisition and Processing in Biology and •. sedicine, New York, 1963. Pergamon Press, Nev York, pp. 103-111.
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295 { 12 P 1963 Do ealignaacies Result from Diagnostic and Therapeutic Radiation? Genetics and the Epidemiology of Chronic Disease, U.S. Dept. of Health, Education and Welfare, pp. 355-371. CEDCObP, Part I, Statistical SYstems. dedical Computing Center, University of Cincinnati, Ohio. Boron, Cadmium, Chromiun, and Nickel in the Blood and Urine. Archives of Environmental Health. Vol 6: 286-295. (H. Imbus, senior author.) Potential Hazard of Exposure to Lead. Archives of Environmental Health. Vol 6: 255:272. (R. &ehoe, senior author.) Carcinogenic Effects of T131 Co®pared with Y-Irradiation - A Review. Health Physics. Vol 9: 1371-1384. (E. Saenger, senior author.) lutomation of Radiation Treatment Planning, III: A Siaplifiied System of Digitizing Isodoses and Direct Print-out of Dose Distribution. British Journallof Radiology. Vol 36: 522-527. Intravenous tlethotrezate (Asethopterin) Therapy in the Treatment of Acute Leukemia. Pediatrics. Vol 31: 834-839. (J. Perrin, senior author.) Eutomation of Radiation Treat'ment Planning, II: Calculation of Nca-Convergent Field Dose Distributions. British Journal of Radiology. Vol 36(427): 63-67. Robot Treatment Planning. Procedures of the Rochester Conference on Data Acquisition and Processing in Biology and Hedicine, Hev' York, 1962. Pergamon Press, New York, pp. 29 9- 3'1 9. m, Robot Data scrEening. Proceedings of the Rochester Conference on Data Acquisition and Processing in Biology and IIedicine, New York, 1962. Pergamon Press, Nev York, pp. 231-242. 0 I H
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k 296 13 1962 ~%. Occupational Exposure to Organic Lead Compounds. Archives of: Environmental Health. Yol 5: 532-536. (R. DaTriville, senior, author.) , . . ..i•. y New Developments in Chronic Disease Epidemiology: Competing Risks and Eligibility. American industrial Hygiene Association Journal. Vol 23: 433-446. ,,_„I' Radiation Epidemiology. Cancer. Vol 15: 489-503. Comparative Studies of Certain Lead Alkyls. Archives of; Environmental Heal'th. Vol 5: 525-526, 532-536. (E. Bingham,; senior author.) 1. _ ,•~ A Practical Procedure for Automating Radiation Treatment- Planning: British Journal of Radiology. Vol 34: 726-733. Epidemiological Hethods and Community Air Pollution. Erchives• of Environmental Health. vol 3: 267-275. (J. Phair, senior_ aut'hor.) _ . -. .;L':• Competing Causes of Death in Coal Tar vorkers. Eettering.— Report. a3: , 1960 Cesium-137 Retention and Distribution in Z-Irradiated Rats.- U.S. lray Hedical Research Laboratory, Fort Knox, 1Centucky.; Report No. 504,. (G. Keriakes, senior author.) Seasonal Variations in the Birth of the tlentally Deficient? American Journal of Public Health. Vol' 501: 955-965. The Lead Content of the Atmosphere. Presented at the 53rd Annual rieeting of APCA, may 1960, Cincinnati. (J. Cholak, senior author.): Yhat Ps ych c Heopli Condi! (E. : Public from Americ Pulnon Vol 30 Tables Kreger senior The A Feedin and Ph senior Source Journa Aborn, Effect Psycho A Cent: Projec A Gen eichig;
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14 Yhat is so Peculiar About Accepting the Bull Hypothesis? Psychological Reports. Vol 7: 363-364. Neoplasia Following Therapeutic Irradiation for Benign conditions in Childhood. Radiology. Vol 74: 889-904. (E. Saenger, senior author.) 1959 Public Decisions and Their Possible Effects on Inferences Drawn from Tests of Significance - or Vice-Versa. Journal of the Aaerican Statistical Association. Vol 54: 30-34. Pu3monary Function in Chi'ldren, I and II. Journal of Allergy. Vol 30(6): 514-533. (I. L. Bernstein, senior author.) Tables of Pulaonary Function Values in Children Ages 6 to 14. iCreger Printing Co., Cincinnati, Ohio. (I. L. Bernstein, senior author.) The Anoreziqenic Action of Deztro-Aaphetamine Sulfate upon Feeding Responses of Differing Strength. Journal of Comparative and Physiological Psychology. Vol 52: 179-182. (P. Siegel, senior author.) Sources of Contextual Constraint Upon Words in Sentences. Journal of Experimental Psychology. Vol 57: 171-180. (l7. Aborn, senior author.) 1957 Effect of Irrelevant Drive on Extinction of Bar-Pressing,. PsychologicaL Reports. Vol 3: 615-618. A Central, Surveillance System neasurement Codel, Part Projeet Michigan 2845, Z914, University of Cichigan. I, I'I. 1 General Survey of Statistical Decision Theory. Project Michigan Z915, University of Gichigan. r'-
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298 cuRRIGULUM VITAE JOHN EDMOND SALVAGGIO Date and'Place of Birthc May 19, 1933; New 0rlcar.s, Louisiana Edocation: ti.I,.H. Re 3. Io•:ola University B.S. 1954 Louisiana State Cniversity School of Medicine M.D. 1957 Postgraduate trainin.g* Intern: Charity Hcspital of Louisiana in New Orleans 1957-1958 Resident and Fellow (Internal Medicine): Louisiana State University Charity Hospital' 1958-1960 N.I.H. Fellcw (I'„.::zunolo8y, Allergy & i.heumat'ology): Departsent of >;edicine, Massachusetts General Hospital and Harvard Medical School 1i961-1963' N.I.H. Special iello. (sabbatical leave): University of Colorado Medical School Immunology 1972-1973 Teaching Appointeents: .aE1 Professor: Louisiana State Universitv School of Medicine, Medicine and Microbiology (Allergv- Rheuaatoiogy Section) 1964-1975 Directorc Interdisciplinary Program Louisinna State University School in of Immunology, Medicine 1'972-1974 Senior physician: Charity Hos?ital at %ew (;~ri?ans 196?-date Visiting Physician: University of Colorado `tadical h l S 1972 1973 c oo Henderson Professor of Medicine: Tulane Medical School, riepartrsent of Medicine - 1975-date N.I.H. Research Activities: 1) Principal :r.vestibator, NIAID resarch grant No. AI 03754, '7fe~.`.anis-s of _c_-rdiaoe and Deiaved ~e~eiti'vity,' 1964-1973. 2) Ptinci'.al Investigator, "Allergic Diseases Canter," grant No. Al 13401, Louisi.:na StateCnicersitv and T.:lane CciversitvMedical Schools, 1973 to date. 4. 5. 61 7. Sc S( A; At y 0 la National 1
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299 Cur:'. m iL --e Jonn =., Sa_:ace o pa,:e '-ao N.I.fl. Research Activities (continued)~ 3. Director,,\ational Institutes of Health Training ^.rant No. TO1-AI~00°_97, LSU Medical Center (Allergy, i-.munology and:Rheumatology Fellows), 1965-1975. 4. Co-Associate Prii:cipal' Investigator, .\'ational i^stituta for Occupational Safety and Hea1Kh, Tulane and LSU Lniversity. Schools of *fedicine, "Studiy of Ittmune Responses in ;dor:ters Newly Ex?osed to Isocyanates," 1973 to date. 5. Co-Investieator, "Immunological Factors in Inte:stitial:Lung, Diseases,"SCOR HL 15399 (Principal Investigator, Dr. Jordor.. Fink, University of Wisconsin and'y+.edical College of xisconsin), 1972' to 1977. 6. Associate Principal'Investigator„ USPHS, HL-6A740, ?ulTonary SCOR Grant, Tulane University School of Medicine "Occupationali and Environmentali Pulmonary Diseases,"'1974 to date. 7. Director, National Institutes of Health Institutional Training ~fi Grant No. 1 732 HL07376, "Training Program in Fibrotic and 4:F Immunologic Pulmonary Diseases," 1978 (5 year acard). Societies: Alpha Cnnega Alpha American t.ssociation for the Advancement of Science New York Academy of Sciences. American Federation for Clinical Research American Acad'emyy of'~ A11=rgy(Felilioc¢). Society for Experimental Biology and Medicine Southern Society, for Clinicali Investiaation American Association for Immunologists American Society for C1inicaP Investi:.ation American Thoracic Society American Rheumatism Association Reticuloendothelial Society American College of Physicians (Fellow) Orleans Parish Medical Society Louisiana State Medical Society \atior•,ali Society Appointments and Offices. 1. Southeast Im.munologv.Society 1969 to date Executive Committee 11 f R q
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300 National Society 1oocincr.tncs and' Cffi'ces (oontih'.:ed) r-,;~..'ci.....' 7..-- :;e. _:,n r.. ...C;~-. Z_io Pa=e M_ee 2~.. Southeastern Aliergyassociatiion1976 Hal M. Davison `lernorial .,-:ard' 3. A.,ierican Thcracic Society . 1977 to 1'978 Governing Council Member (re?resenta- tive for Allergy and Itmunologv) 5, .kl 7. - 4. 'American Thoracic Society 1978 to 1979 Scientific Assembly (A11ergy and Iimnunology). , - .. - . 84. President American Academy of Allergy Program Committee, Scientific Coririttee, Inhalat,on Challenge Corunittee, PoLlen and Mold Committee, Sci'entifie Eshibits Cocmittee, Graduate and Undergraduate Education Comittee 6. Minority Biomedical Support Ad Noc Consultant 7. American Board of Medical Laboratorv_ I:mmunology - ' Advisory.Panel 8. American Tho:acic Society/American Lun¢ Pssn~ Ccm-.)nnent Cortnittee on Research 9. AliergyFoundation.of A'merica Board of Directors Yational~ BnardsandCouncils 1. Journal of Allergy ^ and Clinical Iz. unoloev Editoriali 9card 2. American Board of Allergy and S=-uno1_icga, a Coa!+oint Board of the American 3oard of Intecnal Medicine and the American Doard of PEdiatrics Board of Governors -- 3. ?meri can Bcard of Allergy and I_=unoliogy,, CS-ABL*1 & A3Ped Examination Committee, Cc-Chaira.an 4. P1nerican Bcard of Allergy and I=unoiog.•„ CB-.kBI1H 6 A'BPed President Co-C::aii-an (internal ''edicine)~ National Ins 1. D 2. b 1977 to date 1973 to 1979' 3. 1978 to date 4 ' . ,. :9'2 to 1977 5. 1974 to date 6. 1974' to 1976 7.. 1975 to 1978' 197b to 1978' 1975 to 1380 34-12
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1!. National Heart„ Lung and'Blood ?nstitute 1973 to 1976 Respiratory Diseases Task Force Paneli:denber (ImmunologicaLly mediated pulmonary diseases) 2. National Institute of Allergy and Infectious 1974 Diseases Career Investigator Academic Award (Hypersensitivity Disease) Award'deciined to consider acceptance of depa:t-ment chairmanship which was also su5secuently declined. 3. National Iinstitute of Allergy and Infectious 1973 Diseases Grant Review Speci'al!Study Section 4. Food and Drug :,dhini!stration, U.S. Bureau of 11974 to 1975 Biological Standards Committee 1 ~E (Evaliuation of delayed hypersensitivity skin test antigenss and vaceines)', ,~.'~fi 5. National Heart, Lang and Blood Institute 1975 to 1980 ~I Pulmonary Diseases. Advisory Council, Y,ember 301 ..u_iona1 :~card's and Cous~cils(coni.inuad), utrC_u'_~m Vit~.e ;chn E. ~>1; g_io ? a-e Lour 5. z:,erican Board of Internal ?iedicine 1974 to date Board of Governors and Exaninacion Co=i'ttee 6. American Board of Internal Medicine 1975 to date Co;u cil for Subspecialty Medicine 7'. Arcerican College of Physicians >JCSAP IV Program, Faculty 8. American Board of Medical Specialties 1975 to date National Institvtss of 6ealth Committee Appointments 6. National Institute of Allergy and Infectious 1977 Diseases Task Force Occupational and 'cnvironraantali Ast'ima „ Chair.-an 7. U.S. Veterans Administration Merit Review Study 1977 Section (pulmonary diseases)~ 34-121 0 . - 78 - 20. I !b r~i 6V•, +.'+'if?.=, I
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302 ~." u r~: ..a yP .-._ ..~. Local!hedical Scnool and Hospital Co^unittees (past or p*esent sarvice) . .'lnimal Care Cc^mittee Curri'cul'um Cc,axittee Reeearch Co:,mittee 2' Charity Hospital Cancer Center Coordinating Ccrmittee Human Exoerimentation Committee Radioisotope Comnittee Microbiology Cnairxar.s6ip Search Cc--,nittee . Obstetrics and Gynecology Cnaircanship Search Cor_ictee General Medical Faculty, Clinical Science 2epresentative Military Record . U,S. Aray Active Reserve (Lt. Colonel, `;edicel Cora),1958 to 1950 Hospital Staff: 5. Senior 7aysician (`{edicine), Charity Hospital o`_ Na:: Orleans Consulting Physician (;3edicine), U.S. Veterans Adzinistration Hospital 6. Active Staff (Medicine), Tulane Uaiversity Hcspiral Director of Iaununology Service Laboratory, Tuiane '?zdical School University Hospital (private)l: sero3ogieal, ,isrologic and in vitro ceilular immunologic laboratory nroc2iures. • Board Certifications american Board of Internal Medicine, Dipiocace 8. S American Board of Allergy and Imcunology, CC-A'3I^f 6?S?ed', Di'plo¢ate 9. S 10.
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303 9i3LICG _=.=:'.y. John E. Salva3gi'o..)7.D. 1. Salcaggio, J. and'F. Gonzalez Szvere.toxic reactlio^ss associated with sul_anetnoxjpridazine Aw. Int. Med'., 51(il'):60-67, 1959. 2.: Wilhela:,.R., J..Salvaggio„ and:.Iris. Krupp Ar.aphylactic shock in zynosan~pre-treated guinea pigs (a study on thee pcssitile role of Properdin) Int. Arch. Allergy, 18:31g-3?9, 1961. 3... Salvaggio, J. and E. Crane Severe aliergicreaction after ingestionofacetylsalicy,lic aeidd comDoundsJ. La. State aed. Soc.,, 113c292-294„ 1961. 4'... Saivaggio, J.,.C.A. Arnold,,and C. H. 3anovLong-term anticcagulttion insickle-cell disease (A clinical study.)Sew Eng. J. ?ted., 2fi9:182-186s 1963. 5.Saivaggio, :, J.A. Cavar.augh,.F.C. LoAe11, and S.. LeskowitzA' coapard.son of the immunologic responses of normal and atopicindividuai~s to intranasallyadministeredantia_en - J. Allergy, 35(1).:62-69, 1964. 6. Salvaggio, J.,, A.S. Keitt „ F.C. Lowe11i, and;W. Franklin A'spiiin-induced bronchial asthma. A diagnostic problem J.A.*4.A., 1'88:3^_3,326, 1964. 7.Saivaggio, J, and,S. Leskowitz A comnarison o: the in.-unoloaic resoonsesofnormal.and atotieindivi~i:a_s to pareiterally'injected, alum precipitated protein antigen Int. Arch..Al;ergy, 26::264-2'79, 1965. 8. Salvaggio, J..-M.HL Flax, and S, Leskowitz Studiesin i=unization. III. The use.o_' berv.llGum as a granuloaa- prodUcinc_ agnnt in Freund'sadjcvant J. I:..ouno.., 95(5):846-854:, 1965. p {I G iI !I 9., Slvaggio, J.,, H ka}wan, and,S. LeskovItz- i~ I-.runologi~c responses of atopic and nor-al indivicualsto aerosolized deatran_ I } ~i~! J. Allergy,, 38(1):31i-40, 1966. 10.: Salvaggio, J. - , Nasal aliergydue to inhalant factors. Section in Current. Tberapy H.:Conns Ed., ~:.8. Saunders, Philadel!c::aand London, 1966. . i t i"
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304 ._~.- -_ --,2 11. calr.,.- _io,. Ji., H.A. °uac`ner, J.H. an ...,:q,:a-.oourg E-._asscsis. I.. Prac-_pitins a- :cst :.~....ctsof.ruce `_-sse in tiie serum of patients - - Ann. Int. Med., 54'(4):748-758, 1966. 12'. Klein, R.C., an&J. SalM1aggio - Fonsoecificity of the bronehoconstriotir_g effect ofhista•-ine andace*-yl- beta-rethvlcholinein patients with obstructiveair-av.d'is=-ase J. Allergy, 37(3):158-168, 1966. 13. Salnraggio, J...,, H. Buechner.,, J.Seabury,, andH. aagues;.ack Bagassasis....Ii. Skin reactivity. to crude bagasseextractsand atcpicstarus of patients Int. Arch. Allergy, 31:1-1'3, 1967. -- 14. Salvaggio, J.,, and R'.C. Klein New Orieans,, asthma. I. Characterization~of i'adiviuuaPs invo:ved in epidemics •J. Allergy, 39(4):227-233, 1967. 15. Bailey, G., J. Strub, R'. Klein and J. Salvaggio Dextran-induced anaphylaxis . -•J.A.M.A., 200:999-891, 1967. 16. Salvaggio„ J,., and E. Gastro-Murllilo " Mjrcobacterial substitutes.in "complet.e" Freund's adjuvant. Effect on antibody production anddelayed.hypersensitivity to bovine sercm albumin J. I-_munol., 100(6Y:1340-1352„ 1968. 17. Salvaggio, J., and J.P..Seabury " 9agasse worker's lung Amer. Rev. Res. Dis., 98:724-725„ 1968. 18. Seaburv, J.,. J. Salvaggi~o „ H. Buechner, and V. Kundur °agassesis..111. Isolation of t'ner^cchiiic and mescrnii:c.actinc~vcetesan&fun-<ifrom moldy.bagasse Proc. Sac. Exp. Biol. Med., 129.:351-360~ 1968. ". -.. - 19. Salvaggio, J., andE. Castro-Murillo Autoallergic diseases (Autoitr:unicad:mecanismospaoonenicos). . Acta Medica Costarricense,. 12(2).:165-178, 1969. 20... Salvaggib, J., P.. Arquembourg,. J. Seabury, and H. Euechner Eagassosis. IV. Precipitins.again.st extracts of th'erm.o~hilicactinc- mvicetes in patientsmith bagessosis Amer. J. :4ed.,, 46(4).:538-544',.1969.- 21. Salvaggio,.J., E. Castro-?furillo.,,snd V. Kundur Imaunologie response of atopic and normal individueSsno '-e::holelim9et henoccanin J. Allergy, 44(.6)e344-354, 1969.
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III 305 22., Klein, R„ J. SaYn_ggio, and V.KunCurThe response o.'patients ~.ith "idionat-i'c° cc~cr:cti.e.= _-~~rary disease and "allergic" obs=ructive or3ncnitis to ?redhieWne Ann. Intern. `3ed., 7_1(4):711-718y 1969. 23.Arquembourg, P.C., J.E. Salta3gio, and J.S. Bic.L`ers Priaer off lr_munoelectrodnoresis, with 2n.arpre.arationm.o`.' Patboicgic. Husan Serum. Patterns. S... Karger Co.,,°_asel Swiczerland, `lunich and ... New York, 1970. . .., 24. Salvaggio, J.,,V. Basselblied,.J', Seabury, „ and'li. Heiderscheit Sev Orleans asti~.a.. IQ_ Relationship of clicatoicgic and seasonaD factors to outbrFaks J. Allergy, 45($):25?-265, 1970. 25. SaSvaggio~ J..,., and V. C.[Cundur The usee ofcarrageenaa as agranulbsa-produci~og agent in Freund's adju+ant Proc. Soc. Exp. Eio1i. :4ed'., 134(4)1:1116-1119, 1970. 26. Salvaggio,. J..,.and fi.. Buechner Hypersensitivity di~seesesassociated with precipitating antibody.,. _. In '4vcoticDisease of the L'vr.e„ H. Buechner,. Ed., Ccarles C. Yho-:as Company.,,Srringf'ie1a,.I11., 197,0._, ._ - 27. Salvaggio, J., P. Arcuembourg, and C. Sylvester Aconparison~of the sensitivityy of electr.oi--unodiPfusiord andd si'ng1eradial'diffusicn in cuantitation of iscunoglobulins in dilute solution J. A11'ergy, 4_6(6):326-355, 1970. =8. Salvaggio„ Ji. fiyp,ersensitivityy pr.c.monitis:"Pandors.'sBox"New Eng. J. Med..,, 283(6).:314'-315, 1970. Z9. L: ke, ?:.W..., and J_ S>1•:zg~io , Hvpersensitivity.pneumonitis in Alier.gy, and'1.-aunologySect,on. R. Slavin4 Ed., Tice Practice ofKedicine,.Earperr and'&ow, Publish'ers,. Inc., Vol. 1(Ch. 41). 1971. 30. Salvaggio,.J., L. Zaslow, .1. --reer, and J. Seabury ~ . SewOrleans aathms. 111. Seaiauantitatiroe sercm.etrie.pollen saap?irg.,. u,.1967and1968 ~ Ann..A2lergy, :3:305~317, 1971. - .i 31..Salvaggio, J., and.J. Seabury New Orleans asthma. IV. SEmiouantttati*oe airborne soore sa-nling, 1967 and 1968. • J. Allergy & Clin. hounol.,.48(2).:82-95, 1971. .. . 0 {
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306 32. Salva2_gio; J,.J. Seabury„ and E: Schcen?:ardo - - _:ew Cr'-ansasoh-a.. V. Relat.ionshipLat.ee,-, C,arityHospi~tal astt.:.aand ad.asion~rates,~ samiouantitativepollec and f:::_sal spcre a^,nts., and total particulate aerer..etric sel.pli.^.g dataJs Allergy~6 Clin. L.~uno1., 48(,2):96-114, 1971. . - 33. Bice, D., F.Schvartz, W.. Lake, and J.,Salvaggio The effect of carrageenan on the establisFccent of deiayed hcperaensi, tivitv Inc. Arch..Allergy SAppl. I=unoli., 41:628-636.,1971. 34. Fink„ J'., A.J..Resnick, and Ji. SalvaggioPresence of thernophilSc actinomvicetesin residential heatina-s.•stems Appl. Microbio., 22(4')~:730-731, 197'1. 35. Lake, W.W., D• Bice, H. Schwartz, and J. Salvaggio Suppression of in vitro antigen-induced 1}-phocy.te transfor-ation by J. Irmunol'., 107(6):1i745-175,L, 1971. 36. Salvaggio, J.,, P. Arauembourg, J. Bickers, and D. Bice. - The eff!ect of prolonged plasranheresison imm:unoglobulins, other serumproteins, delayed hypersensitivity and phvtoheaagglutihin- iaduced lymphocyte transforr.ation Int. Ar~ch. Allergy & Appl. I::.aunoL..,.41:883-894„ 1971. 3:, Fink, J., A. Sosman, J. Salvaggio, and J. Earboriak Preeinitins.andthe diagnosis of' a hypersensitivity pneuz:onitis J. Allergy & Clin, Immunol., 48(3)0199~181, 1971. 38. Y.acai, I., J. Salvaggio, W. Lake, and J. 0. Harris Fxoerimental!production of hypersensitivity pneumonitisvith bagpsse andthermophilicactinomycete antigen J..,Allergy, & Clin. Immunol., 50(5):276-288, 1972. 39. Leskowitz, S., J..Salvaggio, an& H. Schwartz Aahypothesis for the development of atopic a1~Lergy in can Clin. Allergy, 2(3):237-246, 1972. 40.B:ce, D..,.D.G. Gruwell, J.E. Salvaggio, and E.O: Hof.`vans Suppression of primaryy immunization bycarrageenan - A.anropcage toxic agent carrageenan,.a macrcoi:age-toxic agent Iawunol. Coma., 1(6):615-625, 1972. 41. Salvaggio, J. - Diagnostic si'gnificanceof.serumprecipitinsi~n hy,-ersansitivdty pneumonitis Chest, 62:242, 1972. • 42. Salvaggio,.J., R. Waldman, M.H..Frunhtcan,.F.M. Wigliey,, and,J.E. J^h^son, Syste~icand secretorv antibody response ofatopi:c and'nen-atopie individuals to intrsnasailyadhinistered'tetanus tcxoid' Ciin.Allergy„ 3(1).:43-4'9,. 1979'. 44. ep C. SalvaR 5. Ce sL Ch Seabur. Ch c 1! '-6. J. Lake,, I7 _. Al: . pg 47~. F.awai~~,. _ 48. Al th Cli Salvag ... Sa no J.. 49. Fawai'~. 0. Pr bv, C'n l<e s s e 1i ~ ,`Re An Ac 511. Seabur 3~~ i 52. My. A-. Cohen „ :~ We Cc. '1 . 53.. Arc.ueY ~ De ISi 54'., Ir' i.ake, - Ir _ ;?. Ali p€'
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307 43., A n-3gio, J., I,Fewai,. and J!. Seaburv.?cc: Orleans epidpmic asths,a: S.emicnantitative aero-etmic car-'_-_, eoiJenioiogic.and i.--munologie studies . , - C'nest, fi3:14„ 1973. 44. Salva¢gio, J.,. T.. Kawai, and J. Harris Cell mediated (Type IV), hypersensitivity in e:<peri--enrainvpersen- sitivity, pnetznonitis Chest, 63:51, 1973. 45. Seabury, J.,. J..Saiva.ggio, J. Doner„ and'T.. f:awai Characterization of thernophilic aetinomvicetes isoiat'ed from resider.- tial heating and humidification svsre_s - J. Allergy & Clin. Immunol., 51(3):161-173, 1973. =6. Lake, W.W:,.J. Salvaggio, H', Buechner Infiltrative Hypersensitivitv. Chest Diseases, inAnncal 3.eviewoc Allergy, 1973, Med. Exam. Publishing Co., Fluseing, N.]., Chapter 13, pgs• 252-294. 47. Kawai, T.,.J~. Salvaggio, J. Harris, and P. Arquembour;g -Alveolar macrophage migration inhibitionin~aniaals i=unized with thermophilic actino:cviceee antigen . _. , -Clin. 6 Exp. Irmunol., 15(1'):123+130„ 1973'. 48. Salvaggio,.J., P. AYo,ueobourg„ R. Waldr.an,.M. S1},, and :'. LopezSalivar,v, nasal'vash, and sputum,IgA concentrations.ir..atopi: an& non-atooicindi'viduals - - J. Allergy 6' CLis. I:mrsnoli., 51(6):335-363y 1973. 49. Kawai. T., J. Sal~aaggioy P. Aiqueab'ourg„ and'~.D~. 2•arsh Precipitating antibodies against organiedustc antige.^.sin hur..an sera bv counterimmunoelectrophoresis C'nest, 64:420, 1973. 50., t.'eisel's,. F., J. Salvaggio,and >!. LopezAnimal ®odeUs of hypersensiticitv pneumonitis Acad. Vet. Allergy Ann.:Meeting (AVAA), 9:58d„ 1973. 511. Seabury, J.H.,. M. McGuinn,, an&d. Salvaggio.. . Mycetona randib'ularis due toFotardia ne'1atieri' A:.~er. J. Med., 55:846-850, 1973. 52. Cohen,.L.K.,. T.F. Thur:ran,.andJ. Salvaggio- Wernerssvndtome Cutis, 12:76, 1973. 53. Arcue!:bourg,. P., M. Lopez, J. Biundo,.anc J. Salvaggio Detection of anti-D'lAantibodies bycounterirnunoe;ectro.i.noresis Ir-+unoiogi'cmethods,,5:199-202„ 1974. 54. . Lake,.W.W:,J.F. F.s'_vaggio and H. °uecl:ner Infiltration c-;perse.^.sitivity. LungDisease, in Aar.ca'- Eevicw of Aliergy,. 1974,.`tec. Exam. Pubi''shing,Co., r^.,usHinS, ~.1`..,. =napter. 11, pgs-ZTO--239, .. jli r.!
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308 3ice,, D., `1. Lopezy H. Sothschild, and J.,S3iz.aoeio - Coaparison of candida-del+ved h;:p~rse^sitivitys:intest size vith 1;-_hocvte transforration, :-IIP ichibitery, '_sctor rro?ucticn and anti'-xlv titer Int. Arch. Allergy & A'ppl'. Inmunol.,, 47:54, 1974. 56.. Gauc.er, H'.R.,J. Salvaggio, K.,t:aston, and H. CPa~an . Cortisol inhibition of i=unplogic activity in guinea pig alveolar exudate celils . Internat. Arch., 47:54', 1974. 57,Karakitsos, R.,,J,. Salvaggio.,,and K. 2dathevs"-"- Conparative nasal absorption of allergens inn atopieand non-atopic subjects - 58. 59. 60. 61. 62. 63, J. Allergy. 6 C1in6 Im¢munal., 55:241,, 19756 Salvaggio, 1., P. Phanuphak, D. Bice, and H. ClaWan - Experinentalproduction of g-anulo:.atouspr.eunonitis - • J. Allerg. & Clin, Iamvnol., 56:364,, 19756 -- Butcher, B., J..Salvaggio,, andG, Leslie --". Secretoryy and humoral antibodyresponse of atopic and non-atopic individuals to intranasally administered antigen Clin. Allerg., 5:33, 1975. Kimura, P., M. Lopez, and J. Salvaggio '. . Characterlzationoftypes of enzyr,atic actdvi'ty.in somatic.extracts of selected fungi, theraophilic actinomycetes andpollen byi~.-nuno- electronhoresis - Clin. Allergy, 5:331-338, 1975. Lake, G. W:, and J~. Salvaggio- - - - Infiltrativehvoersensitivitvchest'disease . - R, Slavin, Ed., Tice Practice.of ?fedicine, Harper and Row ?u3lisners, Vol. V., 1975. [.ei1T,.H., J. Salvaggio, A. Nielseny B. Butcfier.,, andM. Ziskind- Respiratory e:feetsin toluene.dii.socya°ate canufacture:. A culti- disciplinary approach Envir. Health Prospectives, 11:101,. 1975> :- - . - Biundo, J., M. Lopez, P. Rohler, and J.Sa!vaggio . . •Incidence of serumanti'-DfiAprecipitins in.patientswith systemic lupuserythexatosus by counteriarmunoelectrophoresisClia. Allergy, 5:165-174, 197; E5. L 66. 5 67. L 68. H 69. S 71. B 72. c 73. Lc 74'. Bi Phanuphak, P., J. Salvaggio,.Ji. Fink and P. Kohier 64. Incidence of serum~precipitinsabainst organic dust antigens in 75. 1 different populations byy countericnunoe;ectrophoresis - Chest, 68:753-758s 1975.. - -- '
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309 . :U 6.5... Lonez, M.,,J. Salvaggio,.and F..tiessels •- - Ezvircr^ental Ast:a '(microbioiegicai'~ andcli-.arol~~osa'ca1 cc,siler- ations),, in~Bronchial tcstiL:a.: "echanisns snd Ti:era;.utics, ?ubla`~ers Little, Brown, and Conoany,.9oston, _9ass., 1976. 66. Becker,, B., J. Seabury, and J. Salvaggio - -- -' Home-humidifierthermophll~ic actinemycete isolates J. Allergy 6 Clin. Immunol'., 57:174, 1976. 67. Lopez,.M.,.and J.Salvaggio Hypersensit'ivi2y.pneunonitis: current concepts of eticicgcy ard'catno- genesis -- Annual Rev. of Med., 27:453-63', 1976. 68. Harris „ J.0., D. Bi'ce, and J.. Salvagg.io Experimental granulora.tous.pneemonitis: Bronchopulnonary response to M. faeni in the rabbit Chest, 69:287, 1976, 69. Stanford, R., andJ. Salvaggio Experimental granuloratous pneumonitis: Iaaunologie, histologic, an& -ultrastructural corsel~ations- Chest, 69:259,. 1976, - - 70. Kohlier„ P., G.Gross, J. Salvaggic,, and J. Hawkins _ 8umidifierlung: Hypersensitivityy pneuffionitis.related to ther,otoPerant bacterial aerosols Chest, 69:294, 1976. 71. Harris,.J.0., D. Bice, and J. Salvaggio -- Celluiar~ an&humoral broncnopulmonary imaune res:>onses of.rabbits iSmounized with tnere:ophilic actinomycet'e antigen Am. Rev. Resp. Disease,.114:29-43„ 1976. 72. Sal:aggio, J.. andD~ Bice Application of immunologic p:rincipiesto peripheral air;ay"hypersensitivity" 1ung.diseases J. LouisiacaState Medical Society. 128:181-87, 197.6'. 73. Lopez, M, J.. Salvaggio„ ar.d'B. Butcher Allergenicity and iemunogenicityofuasidi'omyeetesJ~ Allergy.6 C1ia. Inmunol., 57:420-88, 1976. 74. Bice, D., J...Salvaggio,.and;E. Hoffmann Passive transfer of experimental hypersetsitivitvpneu-moniris with lymphoid cellsJ~ Allergy6 C1in.. Im<-unol.,. 58:250-62, L976. 75. Lake, W1W. and'~J. Salvaggio Hypersensitivity pneusanitis„ in Practice.of Yedicine,.C::apter 41,. Publishers narper andRow; Inc., iiager.stovn,.*aryland„ 1976, d
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310 87. Schuyle 76. Bice, D., D'. Gruvell, and J.: Sa_•.aggio Ce Inhibition of macrophage migrabicc Sy apla_:afacoor frum cancer patients and norr.ais . J'. Ret~iculoendoth. Soc., 19:281-.89, 1976 38. t_ Davies „ 77. 3utcher, B.,, J, Salvaggio, H. Gei11, and?Y, Z3skind'Toluane: diisocyar.ate (TDI)) pul!~onar;~disease; I:-.unologic Oc J. and inhalation challenge studies 89. Salvagg 78.. J. Allergy & Clin. Immunol., 58.:29-100,. 1976 Kang, K.,.S. Shi¢a„ an&J. Salvaggio . Re J. Study on~the influence of asbestos(aWi'anthus). and Eery,lDiimon 90. Saivagg macrophage of the lung Japan Theory of Resp. Liseases 9ssociationJournal, 14(10):578-584y 1976 An pu Pr 79. Kang, K., and J. Salvaggio 91. Schuyle Experimental study on zizconium~and aluminum compounds . Step.s in Medicine, 98.(10):665-66.8., 1976, Hy H. 80. Kang, K., and J~, Salvaggio 92. Salvagg Immunological E-perimentson Beryllium Pr Steps in Medicine, 98(13):843-346, 1976 r~ A1 81. Rothchild „ H., M'. Wilson, M, Lopez, J. Salcaggio, L evy, and D.Bica ~ 93l Wilson, A immunologic investigation of a.`amilqvith,chror.ic auecocucaneons candidiasis Ae of Int. Arch. A1QergyS Appl. I=munol., 52:291-296,. 1976 J. 82. Kang, K.Y., D: Bice, and J. Saiva3gio °` 94. Davies, Delayed hy;persensitivityy study'on zirconium compoends and . ~ k- . Th. beryllium sulfate MedL J. Osaka Univ., 26 (3-4):131-145, 1976 ~q ~ cy pr+ 83. Kang, K.Y. and J~. Salvaggio J. Effects of asbestos.and'3eryllium compounds on thea.vzoiar 95... Sbarbari mac€onhage :F and E. 1 Med. J. Osaka Univ., 27 (1-2):4'7-58, 1976 Sk: 84. Butcher, B.,, C. 0'`ei1,. H. Weill,. 0.. Carg, and JL Salvaggio Det TolueneDiisocyanate (TDI)') pulmonary disease: I=unopha:racologic .~ 96. Bice,D, and mecholyl challenge studies P.at, J..A1lergy SCl~ih. Immunol~., 59(3):223-227, 1977, ~; J. 85.. t:ang, K.Y:., D. Bioe,.and J. SalNaggio~ >~. 97. Lehrer, ExperimentaL studies on hypersensitiaityto beryllium, z_rconLum, Eli and aluminumsaltsin the rabbit . voi J..Ailergy 5 C1in. I=unol., 59(6):425-436, 1!977 Cli 86. Butcher, B., R. Jones, C..O'Keil, HL Gliindce}•ar,D. Eng, J.Dum, V. Dharmarajan,.H. [deill, and Ji. Salvaggio Long;tvdinal study of workers e=pioyed in the manufacture of Toluens Di-isocyanate >: Amer. Rev.. of Fesp.. Dis•, 116:611-421, 1977. ,
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311 4 87. Schuyler„ M., H. Ziskind, and J. °_alva2~eio Cell cnediated i-i::.unityy insilicosi~s Aiser. Rev. Resp. Dis., 16:147-151,. 1977. 838. Davies., R.J., B.Butctier, and J. Sa1vag¢io Oceupationalasthma caused by lo•..> nolecular~eig}it c.`iE-1'eal agents. J~ Allergy and'C1ia. I=unol., 60(2):99-95, 1977. 89. Salvaggio, J.E. Recertification: Quo Padis?, J. A1Lergy & Clin. Imruaol., 60(3):153, 1977. 90. Saivaggio, J'. Animal models in the pathogenesls ofi=unologicall,vrsdiated pulmonary disease. Proc. Int. Union Tuberculosis, LI(1)2:443-449, 1976. 91. Schuyler, Ml and J. Salvaggio Hypersensitivity pneu=onitic,, is Current Die=_nosis (5th edL)., H.F. Conn and R.B, Conn, Ecs.,,W.B. Sauncers Co „ Phi1S, Pa., 1977, 92'. Salvaggio„ J.E. Present concepts on pathophysiodogyy ofinterstiti4l pneu.^:onopathies Allergology, Proceedings IX'.nternation Oongress,.pp6 369-373, 1977,... 93. Wilson„"l.R., H.R.Gaumer,. and Ji. Salvaggio Activation off the alterr.ative co~olament pathway and generationn of chemotactic factors bvasbestos J. Allergy. & Clin. Imuaol., fi0(4):218-Z22, 1977. , 94. Davies, R.J., B.T. Butcher, C.E. 0'~Teil, and J.E. Salvaggio The •_n vitro effect of toluene diisocyaraate on~ Lyr.phoc.,,te cyclic adenosine monophosphate production by isoproterznol,, prostaglandin, and histarcine: A..possible mode of action J. Allergy & Cli'n. Immunol'., 60(4)',:223-229, 1977 95.. Sbarbaro, J~, C. Cacpbell, 'r. Kantor,. C. Kob'arashi~„ Ji. Salvaa_gio and E. Wolinsky Skin,test antigens; Federal Register . Dept. Health Education and ti:elfare, 42:52674-52723„ 1977. 96. Bice, D:, G.. Heins, D.. Gruwell„ and J. Sa1•:aggio P.abbit alveolar macronhages as indicator cells in ?fIF assays J. Reticulcendoth. Sot. (in press). 97.. Lehrer, S.B., E. Turer, H. weill, and J..Salvaggio Elimination of bagas.sosis in~Louisianap.apert:anu=actu: ngpiant workers Clin. Allergy, 8:15, 1978, - ii. ki ® ®
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312 98.. Cashner,.F., M, Schucler, and J.Sa1-:a3gio.Effect of cortisoneacetateonpulro:ary.lesion.s in a rab'bit~ model of hypersensitivity pnaumonitis . ... Infect. & =ua.. (in~press)i 99. Cashner, F.,. H. Schuyler, and Ji. Salvaggib Iamunologic andphysiologieresponseof primates to~inhalation of detergent aniIB_ Subtilis enzyme Arch6 Env...Health (in press) . - 100. Schuyler,. M..,.and,.J. Salvaggio, Hyoersensitivicy pneumonitis in Clinical Challenge in Cardio, pulmonarv'fedicine. American College ofChest Phy:sicians, Park Ridge, Illinois (in press)~ 101. Stankus, R., M: Schuyler, and J..Salvaggio Bronchopuioonary sensitizing potentiallof alcminum and~zirconi~um 109.. Fink 113'. Lehi l[ sa s Clin. & Exp.. I2munol. (in press). 102. Schuyler, H.,T.. Thigpen, J... Salvaggio Local pulmonaryimmunicy.in.pigeon breeder's disease Ann. Int- ):edl 88(3):355-358, 1i978. 103. Davies, R.J. and J. SaLvaggio~ Diagnosis, prevention and t:anagement ofoccucationaTf asthma Consultant (in press): 104.. Karr,. R.M., P.F. Kohlier,.and J.. Salvaggio -- Hypersensitivityy pneumonitis and'extrinsic asthmar. A case study.of an unusual association~ -Chest (in nresc)~ 105. Harper, T.B.,. W.W. Waring, A.J. Amziann and J.E. Salvaggio Chronic pulmonarydisease and partial cellular immunity, in cartilage hair hypoplasia: Report of a case . , J. Pediatrics (3n~press)' 106. Bicey D'.E.,. K. JfcCarron, E.O. Hoffman, and J. Salvaggio Adjuvant propert3ess of Micropo h-soora faeni'. Internat. Arch. A1liergyApp1'..Imnunol. (im press), 107.Karr, R.M., R~J. Davies, B.T. Butcher, S.B. Lehrer, M.R. Wilson, V. Dharmaral.an, and J.E. Sal•:aggio Occucational asthma . . J..Allergy: 6. Clin. Icmunol'... 61i(1):54-65,. 1978. 108. Stankus, P.., F... Cashner and J. Sal•:aggio Bronchopulmonarymacrophage activationin.the pathogenesis of hypersznsitivitypneumonitis. Ji. Imbunol. 1i20.:685, 1978.
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Bic:'i~~ra-hy. 11 109.. Fink, J.N. and J.. E.Salvaggio„ editorsNIaID Workshop on antigens in hy?ersecsitivity pneumonitis J. Allergy C1'in. Immuinoi. 61(4):199-239, 1978. 110. Stankus, R'. P.,, Y, R. Schuyler, R. A. D"v-.atos and J. E. Salvaggio~ Bronehopulmonarycellular response to alcainumandlzirconium salts_ , Infect. and immun. 20(3):547-852, 1978. 111. Kaug, K. Y.,.P.. D'Amato,.M. Ziskind and J. SalroaggioEffeczs of asbestos and bery.lLium on release of alveolar macrophage enzymes Archiroes of Envi'~ronmental Bealth (in press) 112. Schuyl~er, „ M. R.,. M. Ziskind, and J1. Salvaggio Lymphocyte and monocyte function inn silicosis Chest (scSmitte&for publication). 113. Lehrer, S, B.,, R. M. Karr,and,.I. E. Salvageio Extraction and analysis of coffee beanallargens Clin. Allergy, 8(3)c217-226; 1978. 114. Karr, R.M., S.B. Lehrer, and J. E. Salvaggio Coffee vorker'ss asthma: A clinical appraisal usingRASi J. A1lergyClin. Immunol. (in press). 115. Lehrer, S.B'. and J.E. Salvaggio Charaeterizarion of Theraoaetinomvices saccc.arSantigens infecc. and Immun,, 20(2):519-525„ 1978'. 116. Lehrer, S.B., `!.R. Wi.lson„ an&J.E. Salvaggio Immunogenic prcnerties of tobacco smoke (submitted for puol~ication). 117. Stankus, R. P'., K.Y_.Kaag, and J.E. Salvaggio Macrophage lysosomal enzyme activation in response to~aiuninum and zirconivmsalts (in preparationY 118. Stankus, R.P.,.5.J', Yevich,.M.R. Wilson, and J.E.,Sa?vaggioComplement aetivationand'alteration of F>L1activity, folloving metallic salt exposure (in~.preparation)' 119.. Stackus,R. P. and J.E. Salvaggio Dermal ser.sitizationroaluminum salts (ih preparati'on)
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314 °blishec - 120. Der.son, L. J.,, L. V~ )'._~olitanoj J.. Salvaecio„ and 17, StoofordOccupational dzseese:::`en the workplace is the etiblogpPatienc Care KI(5).:10E-128, 1977'. 1.. Sa'_va@ 121. Aarper, T: B., A', R. Gaur..er, H1B..Liseckl, R..B. Brannon, G, ;, and Ji. E. Salvaggio ' "aring, t;c Fe Aspects of T celli i=unity in children caith~ est's,a: a Con A'induced suppressor. Tcell derect (subcittedfor publication)~ Eve dence for e . Salvag A in Fe Salroag . In de J. Klein ;ro be J. Klein, . '.:e•, un J. Salvag;, 7. An Cl Salvag; . Bai of J. Salvas£ . Bz£ ph. J. Kandar, vii his 7. 10. Salvagg An. Oii
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13' 1. Salvaggio„ J,., :1. Flax, and S. Leskowitz 2Fie adjpvant effect of beryllium on,ornduct of antibody and dela;:ed'hypersaneitivity _ Fed. Proc., 22:267, 1963' 2. Salsaggio,. J., H. Kayrar., andJ. °_abin Aeosparison~of the iamunologic responses of norral and atopic individuals toparenteraily injected: proteia antigen Fed. Proc., 23:402, 1964 3. Salvaggio, J.Ir:munologic responses of atopic and oorWal individua s to aeresoi'ized dextrao J. Allergy, 36(2):194', 1965. 4. Klein R., and J..Salvaggin tionspecifdcity of the broncor.strictingeff,ect of histas,ineand atetyl'- beta methyl choline in patientswith obstructive air~ay disease J. Allergy.,. 36(2):213, 1965. 5. Klein, R., and J.. Salvaggio 5ev Orleans epidemieasthaa:. A clinical comparison of involved uninvolved individuals J. Allergy, 37(2):11i, 1966. and 6. Salvaggio „ J'., H. Buechner, J. Seabury, and P. Srquenbourg. Anti-moldq bagasse precipitins in bagassosis Olin. Res., 14:96,.1966, 7. Salvaggio,.J., H. Buechner, J. Seabury, and P. A.rquembourgBanassosis: Precipitins against extracts of crude bagasse in the serum of carientswich bagassosis . J. A17ergyy, 37(2):'107y 1966. 8. Salvaggic, J, J. Seabury, and H. Buechner Begassosis: Demonstration off precipitins against extracts ofthermo- philic actir.omycetes in thesera of affected individuals .i. Allergy, 39:106, 1967. 9.. Kundur, v., audJS Salvaggio -:=unologiic response to keyhole limpet hematoccanim.GKLH) inrpatients with atopic disease, normal.individuals, and subjects with familyy history of atopyJ..Allergy.,, 41(2):101,. 1968. . 10. Salvaggio, J. Ant-Sbody f,oraaation,in atopie and normal individualsClia. Res.,. 16:44, 1968. ro
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316 -.:cl ed :~s--- ts acont ad). 14, 11~.°al-=_ga.io, J., and V. G. R--r 22. Salvag New Orleans epidemicasthna:. Relatior.shipbet-:een outbreaks and infiuxN2' ofrag•seed- pollien J • J. a1Q'ergy, 41(2)<90, 1968. 23. Sai•.ag 12. Salcaggio,.Ji., P. 2,icuembourg,. J. Seabury,,, and',F:'• 3uechner Ne Bagsssosis. IC,.Precipitims against extracts of thermoID:ni~Lic actino- 19: :aycetesin~patients with bagassosis Ai J. Allergy, 39(3):22, 1970. 24. Saivag: 13. Aleins R., J. Salvaggic, and:V..G...Kundur,~ as The response of patients with "idiopathic" obseructiWe pulmonary . J• disease and: "allergic"obscructive bronchitis to ?recnisene _ - J. Allergy, 39(4):26, 1970L 25. Bice, Sc 14. Klein, R., J. Salvaggio,.and!V. G. Rundur • . _ aa Corticoid trial in obstructive diseases of the lung Fe Mod. >Sed., P. 210, Feb. 23, 1970. 26. Arnuea 15. Arquembourg.,. P., J. Salvaggio, and. D..Bioe ' De Effect of prolonged plasmapheresison~i=nunogiotiulins,, other serum .- C1 proteins and delayed 'nypersensitivity. ,. - Clin. Res., 18:81, 1970. 27. Sa1vaE 16. Salvaggio, J..,,P. Arc.uembourgy and G.Sylvest'sr Quantitation of iamunoglobulins and albumin iad2lute solution by. _, electroi-aunod2ffusion (EID) and siagleradial diffusion (SRD)', 28'. Kawai, Clin. Res.,, 18:84, 1970. Di - J. 17. Salvaggio, J.,, R. Waldcan,. J. Johnson,.F. W"_g1ey.,, and~)1~ Fruchtsan _. ,,. Secretory Igaand ragweed hemagglutinating activity in acopic and '_9L Kac,ai'. normal individuals _ - C' Eaccerpta ?iedica (Internat. Qong.).,, 21:13, 1970., . C- 1'B.. Salvaggio, J. . .. .. . ,. .. ,. , 30. Salvzs "Allergic" reactions.. . . .. h' RewEng. J. Med., 283:820, 1970. __, . . -._ .... a, t, 19. Salvaggio, J., P.Arquembourg „ an&G. Sylvester -- AQuantitation. of immunogiobuliosin dilute so,u^_ion and parotidsaliva-- by electroi=unod2fPusion and'single radial di'iusiow 31:. Salva; J. Allergy, 45(2):128, 1970. D A 20. Salvaggio.,.Ji., W. Lake, D6 Hice,,and'B. Schc:artz-__ . . The ef.`een of carrageenan on delayed hyperse^sitiroitc32.Sa1va C1in. Res., 19:450, 1971. ~ e 21. Salvaggio„ Ji., R. Waldmany P. 9'rnue^:bourg„ and J. Johnson . _ C - Systemic and secretory antii'oodyresponse of atopic andnc.-a1 individualsto intranasally administ'sred tetanustoxoid'J. A11'ergy, 4_7(2),:117, 1971. 34-L21 0
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317 15 Pub1<s:-:ed Abstracts contim:e9). 22. Salvaggio"J'. . New Orleans lstiv.a Seasonal Eoizemics 218(:1):24, 1971. .. 23. Sa1•.aggio, J. and 3. Seabury Sew.Orleans Asti=a. IV. Samiquanti~tative airiorne spore sa.pli,g,. 1967 and 1968' Air Pollution, 2(11):67, 1971. 24. Salvaggio,.J'., A.S..Keitt, F.C. Lowe11, and W. Frankiin Asniric-induced bronchial asthma. , J. Allergy, 29(4):50; 1972. 25. Bice„ D.E., D.G. Grvuell,and J1. Salvaggio Suppressio,, of anti-SRSC antibody.fornation byy car:aeee^an- a aacropt,agetoxic substance. Fed. Proc., 21(2)::929, 1972. - - 26. Arauem.bourg, P'.,J.,Biundb, J. Salvaggie, and M. Lepez Detection of DSAantibodyA bv.counteri*_imunoeieetropnorasis (CIE) Clin. Res., 20(3):505, 1972. 27, Salvaggio, J..,,T. I:awai,W., Lake, and .I. iiarris =:;perimental production ofnypersensitivityf pr,eumonitis Jl Allergy b Clin. Immunol., 4_9(2):102, 1972. 28. Kawai, T.,,P. Arquenbourg, J. Salvaggio, and D. tarsn Detection,ofanti-house dust preeipicins in can J. Allergy & Clin. ImmunoD.,, 49(~):134', 1972. 29. Kawai, T., J.Salvaggio, and J. 0. Aarris . Cell nediated~iseaunity in esperi:mental tiypersensitivity, pneunonitiis Clin. Res., 20t511„ 1972. 30. Salvaggio,. J' , J. Seabury, and _. Schoani:ardt - AevOr'-eans Asthma. V. Relationshipbetueen Cnarity.hos.itab asthma acmission rates, semiauantitativepollen and fungal spore counts, and total ^articulate aerometri'c saapling data- Air pcllution, 3(6):96, 1972. 3L Saii•aggio, J. -. Diagnosticsignifieance of serum, preoipitir.s in 'n;p.erser.si dv'_ty.pneirnrnitisAir PolRution, 3(fi),:96, 1972.. 32. Salvagsio, J., T.. Kawai, and J.. Seabury .- NewOrleans epidemic asthma_. Seruiquantitative aercmetric sa~.pling, epidemiologic.and'imunol'ogic studies - Chest, 6_3:145, 1973. . 34-121 0 - 78 - 21 i~ { 6 ! I E f
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318'. 16 33. 25;:ndb, J..„ J~. Salvaggio, >1. Lcpez, and F.. Sohler - - t etection o'_ anti'-DSA un;ibodiesin.s;s:azie lupus eryfi:ecatesis `oycounteriacu-.oelpctrophoresis (CIE). - ""J. A1lergy & Clin. I--munol'_, 51:101, 1973. 34.. Lopez, H.., D. Bice., and .I.. Salvaggio - Dissociation between aacropHage inhibitionfactor production and '_;zFho- cyte transforation in patients with mucocutanaouscandidiasis" Excerpta Hediea, 300:1'3, 1973. 35. Kawai', T., H.. Lopez, J..Biundos and J~. Salvaggio - . ". Gse ofcounterimunoelectrophoresis(CIiE)f to detect anti-organic dust, fungal and D.WA antibodies in-an. _ . Excerpta Medica„ 300:30, 1973. 36. 3ice, D.,D. Cruvell, E. HullandJ. Salvaggio "-- Inhitdtionofm.aerophage migration by.plasra from patients cith nec- plasms and aged individuals C1in. Res.,, 22:27, 1974. 37. Lopez,.H., D: Bice, H. Rothschild, and J. Salvaggio.- Lackof correlation between lymphocyte transformation and; 'SIF 38. 39.. 40. 41. product':ion Olin, Res., 22:29, 1974. 4 ?utcher, B..,,C. Leslie, and J. Salva;gio Secretoryinmunologic response of atopic andnor.-atopic individuals to,tooicallvy aynlied'antigen - --J. Allergy 5 C1in. I-mmuuo1., 53:115, 1974. 4 ' H: Claman Gaumer,.H.R., J..Salvaggio„ W. Westan,, and Cortisol inhibition of i®munologic activity in guinea pig alveelar exudate cells _. _ Fed. Proc.,. 33(3):789, 1974. -- ` 5 Karakitsos, K.J., J. Salvaggio, and K. Mathews -' Comparativenasaliabsorpt~ion of.allergens in atopic andnon-atopic subjeats 5 J. Allergy & Clin. Immuno1., 5?:y3', 1974.. J. -- Salvaggio , Immunologic response of atopic and non-atooic ihd:viduals 5:I Clia. Allergy, 4:223, 1974. 42. B'ice „ D., D: Gruvell,E..Hull, and J. Saivaggio Inhibition of macrophage migration by plas.a frompatientsc.it:hneo- plasms and aged individuals Clin. Res.., 22(1)a27A, 1974.
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319 --- cts (cc..ati„ied) 43, 5ice, ^i,. '. Salva;gio, and G. Heics. Cozoa:ative r3'togen~inducedly'mphocyte stimula;ion in : .ients:rith nec?liastio diseases -.. Clin.. Res., 2_3(1):2?r1„ 1975. ' -- - 44.. Lopez, M., J. Salvaggio, and'B. Butcher . . . ,~ , . ,. ... Basid'iomycetesas aeroallergens " . - J. Allergy & Clin. Immunol., 55(2):90, 1975. 45. Eutcher, B., J. Salvaggio, H: Geill, and M. Zisxind' Toluene diisoccanate (TDI)') pulmor.ary disease: Seroiogicand i'nhauation chalienge:studies .. J. A1lergy and C1in. Irmunol'., 55(2):129„ 1975. 46. Bice, D.,,J, Salvaggio, and E. HoffJann, Passive transfer of experiaenta.l hypersensitivitypneur.oni'tisvlth 1 Wohoid ce11a ' J. Allergyy and Clin. hmunoi'_, 55(2).:5:1„ 1975.... , 47. Lopez, M.,,P. Kiaura, and J. Salvaggio ' Characterization of enzymatie activity in sos.atic anti^.ens ofselected'fungi'„ th'ernophilic actinomvicetes and pollenby icounoei'ectrophoresisClia. Res.,, 23(1):24A „ 1975. 48.. 3ice„ D., J. Salvaggio,.R. Stanf.ord,.P.Phannpak„ and'.H. Clar.an Ex?erimental production ofgranulc:atous pneumonitis vith?arti:culate thermoohilieactinomycete antigenClin. Res., 23(~1):49A, 1975.. - 49. Idei11, H., 1. Salvaggio, A. Neilsony B. Butcher, and *1. Ziskind Respiraror: effects in toluene diisoc,vanate(TDIY rsanufacture _ EnvironaentaliHealth Prospective, (June, 1975). . ; 50.Bice, D., G. Heins, D. Gru•ae11, and .i. Salvaggio . Rabbit alveolar macrophages ass indicator cePlsin`fIF assays Fed. Froc. 35cfi70, 1976. 51. Bice, D'., J...Sa h•aggio,,6. Hof':f::.ann, and K. McCarron~ Adiuvant eff~ect.of `Licroeolgspora faeni on delayed hypersensitivicy, J. Allerg. and Clin. Immunol., 57(2).:20T, 1976. 52. Butcti'er,. B., C. O'Neil, 0. Garg, H. weiQd, andJ. Salva,ggio. 7oluenedi?socyanaUe (TDI)) pulmonary disease: Im..~unophar:racologic and mecholy.liinh'alation challenge studies . J.dllerg.and Clin.Inmunol.,. 57(3):212, 1976. 4 n e
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18 64. 5 53. .°.arri~s, J„ J..Salvaggio,. R. Staskus Bronchopulmonary icm~une response*_o}ticrnnol~s~ora fazni . 54. J. A1lergy and Clin. Imnunol., 57(3):2=4', 1976. R.Y'. Fang Bi'ce J. Salvaggia D ., E. Hoffman ,. , . . , Studies on delayed,hypersensitivityy to zirconium cerv111un and'~ aiuminumsalts in the rabbit Cliin. Res., 24(3):445A, 1976. 65. Sc Sa 55. Schuyler M. ,J: Salvaggio ?i. Ziskind H', keill , , , , , ll di ed i l~ - 66. Le 56. -ne Ce at mmunityinsi icosis.. Chest 76(3):440, 1976. Schuvler„ '! M: Zi~skind H. 4'eill J. Salw•aegio. 7, , , , Selective depressionoflyuphocyte stimulation in siliccsis Am. Rev. Resp. Dis., 115(4):73, 1977. Stankus R.P. M. Schuyler J~. Salvaggio ' 67. Ra. 8. ,, ,. , Bronchopulnonary celilular sensi'tizing.notential of a1-.:rinua and zi~rconiumsalts.. J~. A1lprgy and Clin. Imnunoil., (In.Press).. Lehrer R.M.Karr J SaLvaggio, S B - 68. Jor H. 9. , . . ., , Anal~sis off allergens present in green coffee bear.s . Ann. Allergy,.38:3^;, 1977. , - Stankus, R.P.,.F.`!. Cashner, J. Saivaggio .. Hypersensitivity pneuaoaitis and cellular hypersensitivity 69. Ann. Allergy 39:76, 1977. . - 70. Sch 60, Cauner, H.R., MIR. LHQson, Jr.,. J. Salvag.gio Activation of the alternative coop+le^aent --oth'.av by asrestoss 71. 9ut fiber Am. Rev. Resn, Dis.,..115(4):56, 1977. , -. . 611. Stankus, R.P., M.R', Schuyler, J.E. Salvag_.ioBronchopulmonary cellular respcrse toaluminu¢~andzircanium , ,. .~ 72.Star.. salts ' _ Olin. Res., 25(1):55A, 1977. 62. Cashner, F.M., `S~R. Schuyler, J.E. Salvaggio _ . i 63. Effect of cortisone acetate on.pulmonarv esions in a.rabbit nodeL of hypersens:tivity pne•.ronitis ._ Clin. Res.,,25(1):22A„ 1977. Stankus, R.P.,, F. M. Cashner, and J.E. Salvagclo Bronchopulmonary macrophage activation in res,r,nnseto "icr^^olys~ora faeni Clin. Res., 25'(1)'.:25A, 1977. ....
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r_o 321 '•-blis`:ec :Sstracts (continue3). 19' 64. Butcher, B.T.,,R,J. Davies, C.E.O'Seil', and J.E..9alva;eio Toluene diisocyanate ouimonory.disease: InhibCtory e.`:ect of TDI upon stibulation of.cA:1P'leveUs by isoproterenoi,, hista :ne andd nrostaglandin.E1. Ann. Allergy, 38:381, 1977. 65.. Sc%iuy.ler,.M.R., H..Gaumer, R. Stankus, J. Y.ai=a1,. E...Iioff=an,. andJ.E. Salvaggio _ -' Pui^_onary aUveolar cacropheges in silicosis- Ata. Rev. of Rasp. Dis.,.117(4).:79, 1978. 66. Lehrer, S.B.,,4.R. Wilson, and J.£. Salvaggio Itmunochenicai properties of tobacco smoke and'Imafd conponents Fed. Proceedings, 37(6)j1456,, 1978. 67. Karr, R.M.,.S.B. Lehrer, B.T. Butcher, J.E. °_a1•:agg.io andHL '.:ei11 Bean hypersensitivity in coffee vorker"sasthna Am...Rev.. Resp.~.Dis., 11~7~('4)~:245y 1978.. 68. Jones, R.N., B.T. Butcher,..J.E. Diemj H... Glindneper, J.E. Salvaggio, and: H. Wei11 Influence of atopy on dust-related bronchoconstriction Am. Rev.. Resp. Dis., 117(4):244, 1978. . 69. Rar., R.H..,.S.&. Lehrer, B.T. Butcher., andJ.E. Salvaggio Investigation of coffee worker's asthca withCne use.of radi'oallergc- sorbent test J. Allergy Clin. I.:runol., 61(3):184, 1978. 7.0.. SchuyPsr, M.R.,. H.R, Gaumer,..R. Stankus, J. KairaL,, and'J.£. Salvaggio Broncticalveolar lavage in siliccsis J. Allergyy and Clin. I=unol., 61(3).:161, 1978. 71. 9utcher, B.T.,.R,M. Rarr, O.E. 0'heil', R.J. Davies, and J.E. SalvaggioToluene diisocyanate (TDI), pulbonarydisease: Studies of inediators and inhalation challenge testing in sensitized Vo.rkersJ. Allergy Clin. Immunol.,, 61'{3)m138, 1978. 72. Stankus„ R.P., S.J..Tevich,. and Ji.E. Salvaggio - Alteration of complement and polymorphonuelear leukocyre activities bpaduminum salits . Fed. Proceedings, 37(6)c1478, 1978 19
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322 t CS)RRICU*A!SVITAE SDZAMrZ B. =oF3E.,. 2(.D.. Date and Place of Birth: Decembar 13, 1926; Fort Wayne, Indiana `` Suzanne B. Present Nationali2ys II.S. - Aeademic Ap Social.5ecuritPN=ber: 313-22-7010 sac: .-Female Present Address: Educaticne Department of Medicine (eontinued) Indiana Uaiversity.SchooL of Madicine - 4 Hospital An 1100 West Michigan Street Zndianapolis, Indiana 46202 Goactiar College A.B. 1948 Inter- DaltSmore, iad. ... national Relations Post-DOetoral TraininS:. Indiana Dniwersity School of Medicine Indianapolis, Indiana - M.D. 1960 Internship: Madicina, indiana University Medical 7/1/60- Center,,tna+anapolis, Indiana 6/30/61 Residency.: Nedicine, Indiana University Medical 7/1/61- Center,. Iadianapolis, Indiana 12/31/62' Fellovshio: USPES Postdoatoral Research Fellow (Cardiology)~, Department of Medicine, Other Aapo. Indiana University School.of Medicine, 1/1/63- Tnd""polis, Indiana 3/31/63 Visiting Fellov. National Institute of Health - 4/1/63- Bethesda,Naryland' 6/30/63 Chi'ef Residency: Medicine, Indiana University.riedical 7/1/63- Center, Indianapolis, Indiana 6/30/64 A++ards • Sr.vestiqator: Heart Research Center, Indiana University Schoolof Hedieine, - 7/1/64- Iadiana?o/is,.l.ndiana _ 3/1/73 Aaademic Tnnointaents: In3trnctor.in Medicine. Indiana University6choo1of Medicine 1964 - 1966 Honorarp S Assistant Professor of Medicine Profession Indiana University.6ci+ool~of Medicine 1966 - 1969 Lxeeutive Offiter,.Departaent of Medicine Indiana University.Schoolof Medicine 1966 - 1971 Associata Professor of MedicineIndiana Universith1..School of Medicine 1969 - 1972 Professor of t!edicine Indiana University School of Medioino 1972 - 1977
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44 323 _ , _ - . Suzanne B. Rnoebel, M.D. Academic ADpointsents: Aasistant Dean for Research (eontinued)'. IndianaDniversity5chool of Medicine 1975 - pres . . o•^^a^ C. and Ellnora D. Xrannert . -. _.-... , .. Professor ofliedicine ?ndia^• Dniversity5chool of Medioine. --1977.-pres Hospital AocointmentsAttending Physician, Indiana Dniversity Medical - Center Hospitals, Indianapolis,,*^dsa^'.. ..... 1964 - pres .. ~ AssociateVisiting Physician, Marion County CeneraL Hospital, =ndianapolis. Indiana 1965 - 1966 Visiting Physician, Marion County General 1967'- pres. . Bospital, Indianapolis,Indiana ' -- Visimq Physici.-in, Veterans A.drniaistration Hospital, Ihd''a^apolis, lnd'_ana . _'... . 1966 - 1974' Other Aneointmentse .. Director,,Cardiology..Marion Couuity General - Hospital,,I^d{anap^lis, Indiana - 1966 - 1974 Attending Physician (Director. Cardiovasoular.- Research), Ver•ras Admitistration.HospLtal mdiaoapolis, Indiana - 1974 - pres Research Associate.. Rrannert Institute of Cardiology, - Indianapolis, Indiana 1964 - 196E Eenior Research Assooiate,. Rraanert Institt:teof , -' Cardiology,.Tndtanapolis, Zndia_^a. 1966 - 197, Associate Director,Rrannert InstitutLe of Cardiology,. Indianapolis,. Indiana 1974.- pree Awards: Physiology. 1956 OS-CYN 1959' Serck Award 19W lSosby.Award 1960 9romen's American Medical Assn. 1960 .. American Boardof. Inter.•a1 eledic+=e, Diplomate 1970 Honorary Soaieties: Alpha Omega Alpha Professior•al Societies: American College of Cardiology,. FellowAmerioan Federation forClihical Research Association of IIniversityCardiologists CentraL Society for Clinical Investigation CounciL on Clinical' Cardiology,.American Heart Association,.Fellow Sigma )Ci II iI C 7
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Suzanne B. Anoebel,. M.D. Offdces and Cormittees: 324 - 3 - Suzanne B. Biblioaran American Journal of Cardiology Tape Journal, ACM ., Associate Edi2or 1969- 1974' American College of Cardiology, LegislatiNeLiaisonCoarmittee 1971 - 1974' 1. Hunter American College of Cardiology, National Self-Assessment Committee 1971 - 1974' fetal American College of Cardiology, 25th ScientificSessionProgram. . Committee,.Co-Chaizman. 1975- 1976 2. Xnoebe American College of Cardiology, Long Range PlanningCOSm ittee 1975- 1976 ccmpli American College of Cardiology, Board of Trustees 1975- 1980 American Collece of Cardiology, Liaison Cosmnittee for Educational Programs 1975 - 1976 3. ]Cnoebe American College of Cardiology, Nominating.Co®ittee 1975 - 1976 American College of Cardiology, Learning Center Committee, Chaiffian 1977 - 1980 4. Fisch, American College of Cardiology, National Continuing Education Programs Coisnitcee 1977 -1980 conduc American Heart Associatitn, Council onClinical Cardiology, Executive. 5. Fisch, Committee 1974 - 1977~ potass American Heart Aseociation, Liaison Committee en Educa".icnal2rogr~ 1975 American Heart Assoeiation, Long Aange Planning Committee of the Clinical 6. Mrsenr Council, Chairman 1977 - 1978: Indian American Heart Association,. Arrhythmia Data Base SelectionCoaittee 1978 NFLBI, ad hoc Committee on.Myocardial Infarction 1972 7. Fisch, NHLBI, MLRU Comaittee. - - 1972 System NfLBI, ad hoc Committee onIsehemic Myocardium 1973 Basel, NELSI, ad hoc Cosanittee on Lethal Arrhythmias . . 1973 NNLEZ, Advisory Committee on Cardiology ,.. 1975 - 1976 B. Enoebe NBIu3I, Research BeviewCosffiittee 1976 - 1980 prable NELBi, Joint US - Italian Committee on "Measurement and Control of Cardiovascular Risk Factors" 1978 9. Arnstr Veterans Administration,.National Merit ReviewCommittee on from f Cardiovascular Diaeases .. 1976 - 1978: 10: Fisch Editorial Boards: -American Journal ot Cardiology 1976 - 1981 . phasic Circulation . 1978.- 1983 Cardia 11. MCNenr cample 8eart . 12. Ncaenr supara. 13. Fisch, and Di Aszhyt pp. 38 14. McNear ooinci Physio 15. Rnoebe bility 60c156 r
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Suzanne B. 1Cnoebel,.M.D. .. Biblioqraphy (Scientific) _ „ .. 1. Bunter, C.,Lansford, K.G.,.icnoebeli, S.B. and Braunlin,.R.J~.: Technique for reeordingg fetal ECG during labor andd delivery. Obstet. Gynec. 16:5, 1960. 2. 1Cnoebel, S.B., &ing, H. and Fisch, C.:Termiz:ation of sopraventricular taehycardiacomplicating the WPW syndrome with external countershock. Cizculation 28:L'1,1963'. 3. Rnoebel,.S.H.e. Ion transport and the myocardium. J. Indiana Med. Ass. 56:165, 1963. 4. Fisch, C., Gre'enspan,.X.,.unoebel,S.B. and,£eigentiaum, e.: Effect of diqitalis on conduction of the heart. Prog. Cardiovasc. Dia. 6:343y 1964. S. Fisch, C., Rnoebel, S.B. and Feigenbaua, H.: The effect of acetylcholine.and potassium on repolarization of the heart.J..Clih. Invest. 43:1769, 1964. 6. Hc3enrl+ P.L. and &noebel, S.B:xSuper,nornal excitation of the human heart. J.Indiaaa Med. Ass. 58:125, 1965. 7.. Fisch, C. and.lCnoebel, S.H.:The effect of Potassium on Atrioventricular Conduction Systen.Eleetrolytes and, Cardiovascular Disease. (E. Bajust,.ed.): S. 1Carger AG, Basel,.5witzerland, 1966, 2:339. 8.. Enoebel. S.B. and McHenry, P.L.: Atrial fibrillation.and digitalis. A complex problem. J. IndianaMed. Ass. 59:135r 1966. . 9. Armstrong, W. McD+ and Rneebel, S.3.: The effect of serum album.in on the efflux of R42from frog sartorius.muscle.: J..Cell Physiol. 67:211,. 1966. 10. Fisch, C., Knonbel, S.H.,. Feigenbaum, . H. andGreenspan, lc.:: Potassium and the meno- phasic action potential, electrocardiogram, conduction and arrhythmias. Prog.Cardiovasc. Dis. 8:387, 1966. - 11. tYHenry,.P.L. and Rnoebal, S.B.: Acceleratlon of the sinoatrial rate leading to complete heart block. An unusual machanism for the Adams-Stokes syndrome. Am. _ Heart J. 72:681,. 1966. 12. HcBenry,.P:L., Rnoebel, S.B. and Fisch, C.: The wolff-Parkiascn-Whitesyndroae with supernormal conduction through the.anomalous bypass. Circulation 34:734, 1966. 13. Fisch, C., Rnoebel, S.B. and Feigenbaun, E.: The Effect of Potassium. Acetylcholine and Digitalis on Atrioventricular Conduction. Mechanism and Theraoy.of Cardiac Arrhythmias. L. 5. Dreifus and W. Likoff (eds.)i 14thHah'nemann Sytipoeiumi . 1966, pp.. 384. .. 14. (icHenry„ P.L. and', Rnoebel, S.B.eThe measurement of coronary blood flow with a coincidenca counting system and asiinglebolus injection of Rb8'(C1..J. APpl. Physiol. 22:495, 1967. 15. Rnoehel, S.B. and Meaenry,. P.L.: Theeffect of potassiianonthe ventricvlar excita- bility.thresholdinpatients wittiimplanted cardiac pacemakers. J..Indiaaa Med. Ass. 60:156, 1967.
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326 Suzanne 8• Suzanne B...R.ioebel, M.D. d "- '- ~ Biblioqras Bibliograchv(6cientific). - continue 16..Enoebel, S.B.,.McHenry.,P.L.,. Steih, L. andSone1,A.:Myocardial~blood flow ia -- 31. Knoebb t t man as measured by,a coincidence counting system and a single bolusot Rb84C1. ' e a.s ow : Fl Circulation 36:1B7~ 1967. . „ -:. , , .-... . , .. , ,... , , ~ 4 ~ . _ and Stein, L•: Myocardial blood flow in McBenry,P.L., Pnberts,.D. S:B. 17 -Rnoebel ' 32. 1D:oeb- , , . man as measured.by a coincidence counting system anda single bolus of Rb$4C1• and t LI W Effect of nitroglycerin. Circulation 37:932, 1968. ~ . 1i972• 18. Fisch, C. andlCnoebel, S.B.: 'Wedensky..Facilitation" and the human heart. Am- Heart J...76:90y. 1968. s 19. Greenspan, 1C., Ed¢'aads,. R.E.. Rnoenal, s.s. ana riscn,. ~•: aome et.... oncardiacautomaticity,.conduction and inotropy. Arch. Intern. Med. 123:707y 1969. 20. McHenry, P.L., Cogan,O.J~, &noebel,.S.B. and Elliott, W.C.: False positive ECG response to exercise secondary to hype=ventiSat:ion: Cineangiographic correLation Am. Heart J. 79:683,1970. , .. , ..,. . 21. Xnoebel, S.E., E1liott, W.C.,.PCss, E. andMeHenry, P.L.: The effect ofcardio, acceleration by right atrial pacing onmyocardial blood flow in normal human aubjects. Cardiovasc. Res. 4:306,1970: 22. Fi'sch, C. and Rnoebel,S.B.: Recognition and therapy.of digitalis toxicity. Prog. Cazdiovase. Dia. 13:71, 1970. . .. , ... 23..Fisch,.C. and Rnoebel, S.B.: Junctional rhythms. Prog. Cardiovasc. Dis. 13c141, 1970. 24..Fisch,.C.,.McBenry,P.L. and lcnoebel, S.B.: CardiacArrhylhaias. Tice's Practice Prnr lishers Vol 6 Chap 4 1970 ub d H i 1 • 33. Rnoeb xther 34. Enoet circc 35. Ronec acute 36. HcHe= treac arte: 37. 2ipe. resp 38. Raoe: flow Circ .p Me icine. azper • •, •. 0 39. Rnoe 25. Davis,. R.E., Rnoebel, S.B. and Fisch, C.: Pacemaker induced, arrhytkmtias. Cardiovasc. Clinics 2:163,.1970. - 40. Fi'sc arrL 26. Rneebel~,5.3. andMcHenry,.P.L.: Myocardial blood flow. Measurement by a coin- cidence counting system and single bolus of84Rb. Arch. Intern. Mad. 127:767, 1971. 27. lmoebel,.S.B., Elliott, W.C., McHenry, P.L. and Ross, E.: Myocardial blood flow in coronary artery disease:. Correlationwith.severity of disease and treadmill exercise response. em. J. Cardibl. 27:51, 1971. 28. Davis, R.E.,.Sehuster, B.., lCaoebel, S.B. and Fisch, C.: Myxomatous degeneration of the.mitral valve.Am.J. Cardiol..28:449,1971. .. 29. Moore, E.N., Enoebel, S.B. and5pear,.J.R.: Concealed conduction. hm. J. Cardial. 28:406, 1971. 30. Anderson,. G.J.., Enoebel,. S.B. and Fisch, C.: Continuous prehospitalization monitor- ing of cardiac rhythm.. Am. Heart J. 82:642, 1971. - 16L,: 41. Rnoe eng, Lss. 42. Tao. el.• 43. Rno• aor exe 44. Eno car art
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327 -6,- Suzanne B. Rnoebel,. M.D.. _._.. _".. . - . Biblioaranhv. (Scientific) - continued 31. rnoebel,,S.B..and McHenxy. P.L.=Myocardial bloodflowincoronaryarterydisease- a steal syndrome? (Proceedings of the Pi'sa,,ItalyConference). Myocardial Blood Flow in.Man. A. Maseri (ed.). Torir.o, 1972,pp.513 32. Knoebel,. S,B..and McBenry.,P..L.: Myocardial bloodflowin coronary artery diseasee andtreadmill~-exercise response. Atherosclerosis and CoronarvHeart Disease. W.Likoff, B.L. Segal~and.E. Insull, Jr. (eds.). Orms and.5tratton,, New York,. 1972,, pp, . 155. 33. Bnoebel, S.B.,Rnoecke, L.L. and Fisch, C.s Paciag,.inaryocardial infarction. Atherosclerosis and Coronary Heart Disease. W. Likoff, B.L. Segal and E. Insull, Jr. (eds.);. Grune and Stratton, New York, 1972, pp. 412. 34.Fnoebel, S.B.,.McHenry, P.L., Phil2ips,J.F. and.Pauletto, P:L.: CoronaiT.col2ateral circulation and myocardialibloodflow reserve. Circulation 46:84,.1972. 38.Konecke, L.L. and Knoabal,.5.8.: Nonparoxysmaljunctibnaltachycardial complicatingg acute myoeardial infarction. Circulation 47:367, 1972. 36. McHenry., P.L., Phillips, J.F. and lcnoebel,. 5.8.:: Correlation of cormpmter-quaotitatedtreadruill exercise electsocardicgraa.s with arteriographic location of coronary artery disease. Am. J. Cardioll. 30:747.,1972. 37. Zipes, D.P. and lDSoebel,.5.8.: Rapid rate dependent ventricular eetopy,. Adverse responses toatropiae-indacedrate iitcrease.Chest 62:255,,1972. . _ - 38. Haoebel,.S.B., McHenry, P.L., Bonner, A.J6 and Phillips,J.P,: Myocardial blood flow in coronary,artery diseaseeEffect of right atrialpacing and nitroglycerin. Circulation 47:690, 1973. 39. Rnonbel,. S.B. and Fiseh,. C.: Concealed conduction. Cardiovase. Clinics 5:22, 1973. 40. Fisch,C., Greenspan, R. and Knoebal, S.B.: Electrophysiolegical basis of clinicall arrhythmias. The Paul Dudley White S-noeium.on CardiowascuAar Disease. H. I. Bussek (ed). Williams and Wilkins, New York, 1973, pp. 309. . - 41. Xnoebel, 5.8. and Duncan,.G.: Mortality study of157.noasargicaleases of c3r.e- aagiographicallydemonstrated coronary artery disease. J. Indiana State Hed. Ass. 67t87" 1974. 42. 7.noebel, S.B. and Fisch, C.: Accelerated junctional escape: A clinical and electrocardiographic study. Cizculation50:151, 1974. . - 43. 1Cnoeoely S.B.,,McHenry, P.L., Phillips,.J.F. andLowe,.D:H.: The effect of aortecvronary bypass grafts oa myocardial blood flow reserve andtreadmill ezercisa tolerance. Cizculation.50:685. 1974. 44. Itr.osbelbS.B., MsBenry,.P:L., Phillips,.J.F. and'Widlansky, 5.:Atropine-inducedcardioacclerationandsry+ocardial blood flow in subjects with and without c•oronaryarterydisease. Am. J. Cardioll. 33:327,1974. 0
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328. Suzanne B.Rnoebel. M.D. . _ Biblio4rachy (Scientific) -- continued . .. .. 45.Lowe, D.R.,RotEbaum, D.A.,.MC=eery, P.L. end Rnoebel,S.B.: Myocardial blood floww response to isametric(handgrip) exercise in coronary artery disease. Circulation51:126,. 1975. . . , ... 46. Rnoebel,.S.B., Pasmussen,S., Lovelace, E. and Anderson, G.J.:Nonparoxy'sral junctional taohycardiainacute myocardial iafaration: eomputer assisted detection. Am. J. Cardiol. 35e824, 1975.. ,47. Rnoebel, S.E. Rasmussen,. S., Noble, R.J. and Mihalick,. N.J.: Nitroglycerin and premature ventrieular complexes in myocardiaL infarction. Br. Heart J. 37:1064, 1975. 48. Corya, B.C., Rasmussen,.S.,.RnoeheL, S.B. and Feigenhaum,.H::. Echocardiographyin aeutemyocardial infarction. Am. J. Cardiol. 36:1l, 1975. - J : and Anderson G 1DLOebaly S H NaHenr P L Rathb m D A J b mem . . .,. . . . . y, au . . .,. .,, 49. No le, R. Noroallzation of abnormal Tvaves in ischemia. Arch. Intera. Med. 136:391,.1976 6. MeHear; 50. Rnoebel, S.H.., Lovelace,. E., Rasmussen, S. and Wash, S.B.: Computer detectionof premature ventricular eompleses: a modified approach. Am. J. Cardiol. 38:44D, 7.lfeHenz* 1976. meat J 51. Lovelace, D.E.,Rnoebel, S.H. aad Zipes, D.P::. Recognition of ventricular extra- .aystoles in sedentaryversus ambulatory.populations. Proceedings of Computers in 8. Am. Pau1a Cardiology. I~ Inc.,.Los Angeles, 1976 pp..9~11. prote 52. Rnoebel„ S.E. and MeHenry, P.L.:. Myocardial blood flow response to isometric - 9. Rasad (haodgrip) exercise: a model for stress coceparisons. Herz (MVnich) 2:27,. 1977.. , to de 53. Corya, B.a.,. Rasmussen, S., Feigenbaum, H., Rnoebel,.S.E. and,Black,N.J.: Systolic 10. Rotti2 thickening and th:nn.+ng;of theseptum.and posterior cra1L in patients with coronaryy artery,disease, congestive cardiemyopathy and atrial septal defect. Circulation iaagi CSrcc 55:109, 1977. - . 11 e Cor 54. Rasmussen, S., Cosya, B.C.,. Feiqenbaum,.H.,Black, H.J., Loveiace.D:E., Phillips, . y find: J.F..,Nob1e,.R.J. and'Rnoebel, S.B..: Stroke volume.caloulated from the mitraL valve echogramib patients with and without ventricular dyssynergy. Circulation (Sup) 58:125. 1978. 12. Miha: PVC 55. Raoebel, S. B., Lowe,. D.R.,I.ovelace ,,D.E. andFriedman..J.J.: Myocardial blood flom.measured by fractional uptake of 84robidium and microsptieres. J6 Nuclear -;r. 13. Bmth Medicine. 56. Rnoebelb S. Zn press. B. andLovelace,.DiE.: A two dimensional clustering technique for i Py84 14. Loxe identification of multiform ventricular complexes. J. Medical Instrumentation. Inpress. - . myoc 15 cor . ] 11 57. Lovelace, D.E. and Knoebel, S.E.: An adaptive algorithm for noise rejection. J6 .~Eelm MEdical Instrumentation. In press. - ~' Cir: Suzanne B. Abstracts 1. NcHenr3 single 2.Ross,.l with a' 3. Stein, on myo 1969. 4. xnoehe and e: artery. 5. ]mo.b. t c
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329 - 8 - Suzanne 8: ttnoebel,. N.D. Abstracts 1. McHenry, P.L. andKnoebel, S.B::. Tha.use of a coincidence counting systemand a sinqle slug technique to.measure coro.^.aryblood flow. Clin. Res. 14:255, 1966. 2. Ross, E., Elliott, W.C., HeHenry., P.L. andKnoebel,.S.B.: Myocardial blood flow with atrial pacing. Cliin. Res. 17:2fi1,. 1969. 3. Stein, L., Boss, S. and Knoebel,.S.B.: Effect ofisoproterenol and eorepinephrlae on myocardial blood flow in experimentalcardiogenib shock. Am. J.:Cardiol.23:140,1969. 4. lswebel,5.9., Elliott, W.C., XcHenry, P.L. and Ross, E.. Myocardial blood flow and e:ereise electrocardiogram in cihe arteriographically demonstsated coronary artery disease.,. Am..J. Cardiol..25:110, 1970. 5. KiwebelL9.B.,. MeHenry: P.L., Phillips, J6P. and Jacobs, J.Ju Objectiveassess- nunt ofsaphenous vein bypass surgery. Circulation 43 6 44 (Suppi.. ii).c187.,1971. 6. McHeary,,P.L. and Knoebel, S.B.: Myocardial blood flow in coronary artery disease - a steal syndrome.. Gteulation 43 a 44I(Suppl. 1S)s199, 19711. 7. NcBenry,,P.L., Rsoebel, S.B. and Phillips, J.F.: Correlation of degree of S-T sag- sent depression during erercise with presence and type of coronary artery collateraU. Am. J. Cardiol. 29:276,. 1972. _ B. Pauletto, J.J., NcHenry,.P.L. andIQ:oebel, S.B.:Treadmill exercise versnsiso- proterenol (IIsuprel) in ECG diagnosisof coronary disease. Clih. Res. 20:771, 1972... 9. Rasmussen,. S. andSnoebel, S.B.:. The response nf premature ventricular complexas to decreaaed venous return. Circulation 45 a46 (Suppl. IV):234, 1973.. . 10. Rothbaun. D.A.,.viellman,H.R., Lowa,D:K. andl0zoebel, S.B.a RubidiumQ1 myocardial imaginq: correlation withelectrocardiogram and coronary cineanqiography: Circulation 49 6 50 (Suppl. III):243, 1974. 11. Corya, H.C., Feigeabaum, H:, Rasmussen,. S. and Knoebel,.S.B.: Eehocardiograp)v.e findinq precedinBmortal3ty in acute cryocazdial infacetion. Ciseualtioa 49 e 50 (Suppl. III):29., 1974'. . 12. Mlbalick, ri.J.,.Rasmussen, S. and Rnoebel, S.B.:. Theeffoct of nitroglyeerin on PVC in acute myeear3ial infarction. Am. J. Cardiol. 33:157,1974: 13. Bothbaum, D.A.,. Lowe, D.K.,. Wellman,:S.R. andlcnoebel,. S.B.:: Comparison between Rb84 myoeardial blood flow and Rb81 myocardial scaa. Clin. Res. 22:597a, 1974. 14. Lowe, D.K.,.Rothbaum, D.A., HcHenry,,P.L. andKnoebel, S.B.: Handgripeffect on sryoeardial blood flow. Clin. Res. 22:630a,.1974'. . . 15. Corya, B.C., Rasmussen, S., Knoabel,.5.8., Black, M.J. and Feigenbaum, H.: Echoeardiographie leftventricular function related to coronary.arterydisease. Circulation 51 0 52 (Suppl. II)',:133,1975. . . .. , . p,hl,l. I 0
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330 - 9 - Suzanne B. '.Cnoebel. M.Di Abstracts - continued . 16. Bothbaum.D.A., Lowe,.D.K.,,. Kephart,.J. and Knoebel,S.B.: Comparisonof 84Rb and~ microsphere total blood flow deterninations with coronary artery,ligation and isoprotarenol. Clin.: Ras. 23:206a, 1975.. . 17. Fssmussen, S.,COrya,,B.C., Feigenbaum, H., Kaoebel,.S.B. and B1ack,.M.J.s Sys- tolic wall thickening and thinniag in patients withceronary artery disease. Citculation 53s 54!(Suppli. II):189, 1976. 18. Corya,.B.C., ++as*u-sen, S., Lovelace, D.E., Noble, R.J., Bl.ack, M.J., Knaebal,S.B. andFeigenbaum, H.a Correlation of echocardiographic calculations withh stroke volume in patients in a coronary care unit.. Cizculation53 t 54 (SuppL. 11);:233, 1976. 19. Corya, B.C., Rasmussen, S.,.FeiFjenbaum„ H.,B1ack.,M.J. andKaoebel, S.B:c Echo- eardiograpbiedetection of scar tissue in pati.nts with eoronaryartery di'sease. Am, J. Cardiol.. 37:129,. 1976. _ . 20. Rothbaum, D.A.,.Wellmaa,.E.R. andEnoebal. S.S.s Clinical implications ofmyo-cardial perfusion scaaning iacoronary artery disease. Am.:J. Cardiol. 37:168,. 1976. 21. Wakefield, D.L., Rothbaum, D.A.,Faris,.J.V., Wellman, H.R. and Knoeliel,S.B.a Honinvasive left ventriculography in coronary disease: evaluation of the nitro- qlyeerine ventsiculogram.. Am. J. Cardiol. 37:179, 1976. 22. Rasmussen. S., Corya, B.C., Feigenbaua, B. andKaoebal. S.B.:e Left ventricular wall motion ih subendocardial infarction evaluated by echocardiography. C1ia. Bes. 24s237a,.1976. 23. Faris, J.V., Burt, R.W., Graham,. M.C. and Knoebel, S.B.: Computerired'statistical enhancement af stress Thallium-201 images. Circulation55 F56(Suppl. I3'S).:140,. 1977. 24..RUffy,. R., Lavelace, D.E.. 1Cloebelb S.B.,. Eiw.rre , V. and Zipes,. D.P.: Relatiom- s1¢ip between left ventricular electrograms and regional blood flow in acute ,. myocardial ischemia with and without stellate stimulatiom.. Cizculation 55. (Suppl. III):529. 1977.: 25. 1C:oebel. S.D. andLovelaee,:D.E.: A two dimensional clustering technique for identification of multiformPWC. Presented to the Association for the Advancement of Medical Instrumentation 13th Annual Meeting,.4iashington,D.C., 1978 _.. ., . 25. Rnoebel, S.e. and Lavelace. D.E.: Anadaptive algorithm for noise rejection. Presented to the Association for the Advancement ofMedieal Iastrumentation 13th Annual Meetin q Washington, D.C., 1978. 27. Paris, J.9.,.Burt. R.W., Grah=,,M.C. and Knoebel, S.B.:. Improved sensitivity_ in detecting coronary.artery disease using.computerstatistical analysis of: Thalliusr201 scans. Fresented;tothe.5ociety of Nuclear MedicineAnnual Spriag Meetinq,. 1978. Name: Sherwin J Address: Social 2 La1ti w0tert Phone: (617) 9, Social Security Citizenship: Ar Specialization: Education:: Har Mak Afr Soc Lor (Sc an( Sy) No, Languages: En Fr Ki Sw Empioyment and Dates I 2/70-pres 1/70-pres 1/70-pres 28: Lovelace, D.E. and Knoebel,, 5.8.: Operator assisted automated review system for 44 aebulatoryECGrecording. Accepted forpresentation at the annual meeting of the 9/72-6/77I.E.E.E. 'Computers in Cardiology.' ~
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331 Curriculum Vitae of Sherwin J. Feinhandler Name: Sherwin J. Fei'nhandler Address: Social Systems Analysts 2 Calvin Road Watertown, Mass. 02172' Phone: (16171924r1611Social Securi3y-No.: 360-26-2761 Citizenship: American Home: (617) 969-5347 Specialization: Cultural and Social Anthropology; Linguistics; Language and Communication; cognitive and meaning systems; Tobacco, alcohol and drug research; program evaluation; Ethnography of everyday life . Education: Harvard University Makere College (East African Institute of Social Research) London University (School for African and Ori'ental Studies) Syracuse University Northwestern University 9/58-12/67 Ph.D., Social Relations 7/60-12/62 Associat'e 7/60-12/60 Special Student 9/56-6/58 M,A., Anthropology 4/53-6/56 B.A., Sociology Languages: English: Speaking, reading and writing French, German: Speaking, reading Kikambaz Speaking Swahili: speaking, reading and!writing Employment and Research Experience: Dates Title Institution 2/70-pres Director Social Systems Analysts 1/70-pres' Lecturer in, Harvard Medical School Anthropology Dept. of Psychiatry 1/70-pres Assistant Dept. of Psychiatry Anthropologist Massachusetts General Hospital Responsibility Admi'nistrationy research and consulting n E M Research in verbal and „ `0 non.verbal' behavior Coordinator of, Alcoholismi Training,Program to 1971. Supervisor of Street Youth Program to 1973,. consulting 9/72-6/77 Lecturer Simmons School of Research Seminars Social Work 94 11 ~
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332 S. Feinhandler Date Title Institution 1/70+6/73 Adyunct~Asst. Dept. of Anthropology Professor Boston University 6/28-12/69 Assistant Division of Psychiatry Professor Boston University School of Medicine 9/67-12/69 Assistant Dept. of Anthropology Professor Boston University 1/68-5/68 Research H.S.G. Cutter Associate Brockton V.A. Hospital Brockton, Mass. 3/65-12/67 Research L. 2. Sherman Assistant Brockton V.A. Hospital 1/61-11/62 Ethnographer East Africa C. 0. Frake, Supervisor 9/59-6/60 Research R. F. Bales Assistant Harvard University 1/59-9/59 Research M. Orne Assistant Mass. Mental Health- Cent'er 1/59-6/60 Researcher M: Orne 10/57-4/58 Research N.Y. State Mental Health Assistant Research Unit, Syracuse 10/56-6/58 Instructor Syracuse University 10/56-12/57 Researcher G. Agogi'no 12/54-4/55 Statistical R. F. Winch Assistant Northwestern University. Consulting,Experience: - - Responsibility. Teaching -2: Diirector of Evaluation, of a Housing Program Teaching, Researchion alcoholism and comnunicat'ions Researchion alcoholism and social structure of the hospital„ Research',with primary focus onicogniti've anthropology, social structure and medi'cine Researchion inter- personal behavior Experiments on trance Fieldistudy of Penecostal ' church'es Researchiin Schizophrenia Teaching _ Archeological Digs Analysis of data Dates Institution Responsibility 11/73-2/74 National Institute on Alcohol Study of bar behavior Abuse and Alcoholism, 6/73-10/73 Mass. Committee on Criminal Evaluation of delinquency Justice prevention practices S. Fe Dates 6/72= 3/72- 3/71• 4/71F 5/71. 4/70 9/70 11/6 1/67 5/66 3/65 Cour Ir.t- Inti Inti IntE Den FolO Prir Lan, Med Ant' Res Pro Horn '9_S Fel For
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333 S, Feinhandler -3- Dates Institution Responsibility, 6/72-6/73 Cross-National Drinking Survey of Drinking Practices. 3/72-12/72 Practices Mass. Committee on Criminal Evaluation of methadone day- 3/71-9/72 Justice Division of Drug Rehabilitation care program Evaluation of Marathon House,, 4/71-6/72 Commonwealth of Mass. Beth Israel!Hospital a drug rehabilitation program Dept. of Labor Study of Job 5/71-7/711 Boston University School of Imp,rovement' Proposal for comprehensive Medicine, Division of Psychiatry treatment program for alcoholism ® 4/70-12/70 Harvard University Programion Designed and conducted'survey of 9/70-8/71 technology and society Barss, Reitzel and Associates public attitudes or1 technology. Office of Education M l 11/68-10/69 Harold'.Cabot Co. Library Program Evaluationi Studies of Consumer Cognition 1/67-6/67 Boston State Hospital: and Behavior Proposal Treatment' and Research 5/66-7/66 Harvard University School of in Alcoholism Curriculum Development on East II 11 3/65-9/65 Education Charles MacArthur Africa Study of Smoking, behavior and P ~ Harvard University Health Services cognition 11 Courses Taught: Introductory Anthropology (1-year course),, Syracuse Whiversity. Introductory Sociology ('1-year course), Syracuse Universit'y. Introductory Statistics (assisted~lecture and lab), Syracuse University Intermediate Statistics (assisted lecture and lab), Syracuse University Demography (lecture), Syracuse University Folk Systems of Classificat'ion (seminar), Boston University Primitive Religionjlecture)',, Boston University Language and Culture (seminar), Boston Uhiversity Medical Anthropology (seminar)', Boston University • Anthropological Linguistics (lecture), Boston University Research Seminars, Simmons Schooliof Social Work Program Evaluation. Antioch Institute of Open Education Honours:' ss7~isi'ant Editor, Deltan Fellow, Social Seience in Medicine, Harvard University, 9/58-1/61 Ford Fellow, African Field Research, 1/61-6/62 41' 0 0 a rsa V N 59 M iM Is, s M 3A-121 0 - 78 - 22 IVA
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334 S. Feinhandler -4- Professionally Related Experience: -S. Feinh'anc Nardt, R: a Relat Confe Leading therapy group of wives of alcoholics Feinhandler Leading therapy group of married couples ., Famil Leading therapy group of alcoholics Leading,"T"' group of Psychology Trainees (graduate students). Evaluating referrals on closed circuit Telediagnosis System Curriculumidevelopment Professional Memberships: Fellow of the American Anthropological Associ'ation Society for Ethnomusicology International African Institute Fellow ofithe Society for Applied'Anthropology Society of, Medical Anthropology Publications: Agogino, G. and S. Feinhandler. 1957 Amaranth Seeds from a San,Jose Site in New Mexico, Texas Journal of Science. 154-156. Freeman, L., Agogino, G., Feinhandler S. J. and'N. Goldman. 1957 Further New Concepts in Family Sociology. Deltan. Spring. Feinhandler Famil Feinhandler Brocl 1! Mass< i! Annui 1'. St. I 1! Uect Hardt!, R. and S. J. Fei'nhandler. 1959 Social Class and Mental Hospital'Prognosis. 1' American Sociological Review. 24:815-821. Inno Feinhandler, S. J. 1969 An1waluation of the Human Side of a Housing Rehabili- . 1 tation Program. In Innovations in Housing Rehabilitation. M. R. Levin4 ed. Scie Pp. 48-52. Boston: Boston University Press. . 1 Feinhandler, S. J. 1969 An Evaluatibrc of the Boston Rehabilitation Project. Annu Monograph submitted'to the Department of Housing and'Urban Developm.nt. To be published as a government paper. Chaftez, M. E., Blane, H. T. and 5. J. Feinhandler. 1971 On the Training,of Leaders in Alcoholism~ In Recent Advances in Studies of Alcoholism. Mendplson and Meltoj eds. Pp. 845-862. Rockville: N.I.MiH. Armor, D. and S. J. Feinhandler. 1971 How People Perceive Technology. In, Program on Technology and Society, Sixth Annual Report. Pp. 21-24. Cambridge: Harvard'University Press. Feinhandler, S. J. 1971 A Cross-cultural Study of Trance. New York: American Psychological Association. Feinhand4er, S. J. 1972 An Alcoholism Training Program from the Partieipants" Point of View. American Journal of Orthopsychiatry. 42:318-319. Papers Read at Meetings and Invited Lectures: - Agogino, G. and S. J. Feinhandler. 1956 Report on the Earliest Cultural Affiliation with Amaranth Seeds in North America. American Association for the Advancement of Science. Dec. Hardt, R: and S. J. Feinhandler. 1958 Social Class and Schizophrenia. New York State Sociological Society. May. . 1 psyc 1 Univ 1 Soci References Prof. RobE Prof. How Dr. MatthE Prof. Harc Dr. T!. Har Prof. WiiP Med• Prof. Helk Dr. Emil I Prof. Lew'
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335 S. Feinhandler -5- ' Hardt, R. and S. J. Feinhandler. 1958 Some Social and Clinical Factors Related to the Duration of Hospitalization. New York State Inter-Hospital Conference. April. Feinhandler. S. J, and J. Orenstein. 1959 Recent History of the Extended Family in India - Part I. Southwest Social Science Association~ October. Feinhandler„ S. JL and J. Orenstein. 1959 Recent History of the Extended Family in India - Part II. American Anthropological Association. October. Feinhandler, S. J'. 1966 Diagnosis and'Treatment in an East African Tribe. Brockton V.A. Hospitali. 12th Annual Lecture Series. Feb. . 1967 Some Ethnographic Observations.on Drinking. Seninar on Alcoholism. Massachusetts General Hospital. 1967 Effects of Alcohol on Behavior. Brockton B.A. HospitaJ. 13th Annual Lecture Series. . 1967 Diagnosis of Disease and Healing Categories in East Africa. Court St. Regional V.A. Hospital. July. 1967 Transcultural Psychiatry. Taunton State Hospital. Psychiatric Lecture Series. Oct. . 1969 The Human~Side of the Boston Rehabilitation,Project. Institute of Innovative Techniques in Housing. Boston University. Jan. - I . 1969 Conflict and Conflict Resolution in a Housing Program in Roxbury. Scientific ColloquiumL Boston University School of Medicine. Sept. 1971 A Cross-cultural Study of Trance. American Psychological Association. Annual Meeting. April. . 1972 Evaluatfon of an Alcoholism Training Program. American Ortho- psychiatric Association. AnnualiMeeting. 1973 Drugs and the Counter-culture: An Anthropological Approach. University of, Rhode Island. Police Training Institute. June. 1974 An Ethnographic Approach to the Streets, Drugs and Drug Treatment. Society for Applied Anthropology. March. References: Prof. Robert F. Bales, Social Relations, Harvard University Prof. Howard T. Blane, Dept. of Psychology, University of Pittsburgh Dr. Matthew P. Dumont'. Dept. of Mental Health, Coamonweal!th of Massachusetts Prof. Harold Fleming, Dept. of Anthropology, Boston University Dr. T. Harford, NationaliInstitute on Alcohol Abuse and Alcoholism,.RockviilJe, Md. Prof. William Malamud, Jr., Dept. of Psychiatry, Boston University School of Medicine Prof. Helen Reinhertz, Simmons School of,Social Work Dr. Emil Rothsteiny Associ6te Chief of Staff, Brockton V.A. Hospital Prof. Lewis J. Sherman, Chairman, Dept. ofiPsychology, University of Missouri
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336' tcS CIAL SYSTEMS ANALYSTS (s1n s2a-1s» 2 CAL VIN, ROAD, WATERTOWN,' MASSACHUSETTS 02172' social SystemsAnaly.sts has successfully conducted work in areasrelatedto,socib-culturali and behavioral issues si'~nce. . , February of19706 Types of projects inciude:. -. - basic research - program evaluation, . . = surveys of - planning - pubLic.attitudes - management oriented - training, information systems Specif~ic content areas have ihcludede mental health - drug abusejuveniledeLihquency tobacco ageing, housing employment - criminal justice - alcohol use and abuse - community social structure - service del~ivery- learning and language disabilities . - technology. - energy use.. .., PARTIAL LIST OF CLIENTS Pederal - Department of Housing and;Ueban Development - Office of Education - National Institute on Alcohol Abuse and ALcoholism. - Nationali Institute on Drug Abuse. State andiLocal- Arlington Council on Ageing BM I. :RA B.A k.5 Ph. .I'1. TEA ' Z92 Z83 -- - - - Massachusetts Committee on Criminal Justice Massachusetts Defenders Committee Massachusetts Department ofMental Health - Massachusetts Div.ision,ofDrug Rehabilitation Educational. - Emerson College,,Robtiins Speech and Hearing.Clinic - Harvard University Prog.rarion Technology and~Society - Harvard Universi~ty School of Education 794 - New Brunswick PublicSchoo1System_ . - UniversityofMassachus.etts - Universityof~ New Brunsvick ' Z94 Private - Barss,.Reitzeli Reitzelland AssInc. . , . . - Harold Cabot andCo,,. Inc. Z94 - Insti~tuteof Canadian Bankers - Massachusetts Association ofGeneraliContractors - ria55achusects General Hospital . - Philip Nonr.is Incorporated Z9$ - Research~.Triangle Institute
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337 CU.;L4_CULIM VISAF of DR. WAvTE? lA. 800:{ER BIRTH DA.£: BOr'!ff*r:R 4, Z,4C8 BrRlB PLACE': LITTLE ROGX, AFi:Y.4NSAS B.A. Alorahouse CoZZege, AtZanta, Ga. Z928 ,FI.S. L'niversity of Iooox, Z932 Ph,D. Lhiversity of Chicaco, Z942 ~. TEIICHING EXDER,-7^E 1'928 - Z929 Iristructor in BioZogy and Chomatzy, LeZand CoZZege, 3akrr, Louisimra ZS32 - 1943 Insti-<ctor in BioZogy and Chenistry, Prairie V•:.ed CoZZeae, Prairie Viem, Tesas; Head of Departnent of BiologiasZ Sciences, Prairie Vicw CoZZe3e. Z943 - 1944 ~ Instruator in Phm+rtacoZogy, Howard Uni, ersity, CoZZege of Medi,-iw, (Left Prairie Viera vith rank of Professor of PkysioZogy). 7.944 - 1948 Aasistaxt'Professor of Pha*naeoZogy, Howu•d University. Z948 - 195: Associate Professor of Phca•macoZog~j, Howard L'nivarsit•y. Z9S3 - Z954 Acting Head, Depaz°Srnent of P&crmaccZogr, Howard flniaersity. 1s
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338' TEACHING EXPEP.IENCE - GTiNT'D. PUBLIC 1954 - Z973 Professor & Chaismas, Deparbment of PhramzcoZogy, 8oward University. Z973 - Present Professor of PharmacoZogy, Haaard University, Z. CA Ci 2Y^ III. lffML7RSSIPS. - Co . The Ameriazn PhystioZogi.caZ Society The American Soc-iety for Ph[anacoZogy and'~•^perimentat Therapeutics The American Society for CZiniczZ'Phaz+nacoZogy The Sig+nz IZ Scientific Society The Endocrine Society The Ameriauc CoZZege of CardioZagy SPECIAL HONORS - Ac An Ch Ar; St: go+ Fsn Tht Re, (At Rer Senior FuZbright Scholar in Bei:gium (Ee,;vuzns Inst'itute) Z957 - Z958. Abc 2% . Representative of the American Society for PFca-rnacology and FsperinaentaZ Therapeutics to the HationaZ Research Counei.Z, Z959 - Z967. Th6 Pra ~ - Chairmon, Cornemittee on Resem+ch, CoZZege of Medicine, Howard University, Z955 - Z969. Chairmm:, University-Wide Committee on Hionaz Researeh, &xaard University, Z970 - Z973. Chairman, MadicaZ SchooZ Cararrittee for Hwnan Research, Eomard University, Z966 - Present. Member Research Comrtittee, Washington Heart Association, 1966 - Z97Z, Chai{rrian, Z97Z - Present. Menber of Board'of Directors, 1Aashington Heart'Assoeiatian, 4he' Prc Pta Per Stu The Act Use Ass Phu Z969 - Present. Member of Board of Advocates of Meharry, Medical CoZZege, E'ashviZZe, Tennessee, Z972 - Present. FaZZow, Ameriaas CoZZege of CordioZogy, Z973 - Present.
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339 PUBLICATI01'S: 1. CARDIO4ASCULAR CircuZatory,and Respiratory Effects Resulting from Dawnward Tracttion on the Liver (Demonsvated before the International Congress of Anesthetics), Anesthesia and Anatgesia, 2941. Anesthesia and Analgestia, JuZy, Z943. j' Acute Effects Resulting from Dow,m:ard 2haction on the Liver, Chronic Effects Resulting from Dowtauard Traction on the Liver, Archives of Surgery, July, Z943. Studies in Abdcmi.naZ Distention, Anesthesia and Analgesia, November, Z544. Further Studi.es on the Acute Effects of Intra-Abdominat Pressure. The American Journal of Physiology, May, 2,947. Renal Function as Related in Increased Intra-Abdominat Pressure (Abstract) Federation• Proeeedi.ng3, Maeh, Z948. Renal Function Related to Acutely arud CJironieaZZy Raised Intra- Abdomi rn'na lnal Pressure in Anesthetized Dogs. American Journal of PhystioZogy, October, Z95Z. The Effects of Cortisone on the IsoZated and Intact Heart'. Proceedings of the British P'hysioZoginzl Soaiety; JuZy, Z956. The Action of Some Cardiac Lrugs on the Heart During Hypothermia. Proc. of the Int'ern. PhysioZ. Congress, July - August, Z956. FSarther Studies on the Effects of Cortisone on the Isolated Perfused Rabbit Heart; Relation of Potassiwn. Ibid. Studies on the Acute Toxic Effects of Cortisone on the Heart. Ibid. Pharm. et' Therap., January, Z960: The Effect of ATP on Heart Action; Relation to CatecIzoZamine Action. (Abstract) Fed. Proc., March, Z959, (an:th D. Ed,oards) Use of the Isolated Ferfksed Cuix,ea Frb Heart as a Biological 'Assay Method for Adrenaline and Ror-Adrenaline. Arch. Int. da
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340 CARDIOVASCULAR - CONT'D. CAl'"r'CHa Conpc=ison of the Action of Epinephrine and Nor-Epinephrine Sent on the IsoZated Perfused Guinea Pig Heart During Normothermia to 1 and Hypotherm::a. Ibid. Februaz^y, Z960: Compra-ison of the Action of Epinephrine.and Nor-Epinephrine ~ Stu Against Cocaine Depression in the IseZated Heart During the Normothermia and Hypothermia.''Ibtid. Lars PossibZe Use of the IsoZated Perfused Guinea Pig Heart'as an Pur Assay for Angiotensin. Mari.Zyn Watson and WaZter M. Booker, in Fed. Proc., March, Z965. Law Studies on the Possible Sensitization by Nicotine of the BZood Fta` Woodrow MitcheZZ and Pressure Resporse to Catecholmrrines met' . Walter M. Booker, PharmacoZogist, August, Z965. 12: Further Studz"es on the PossibZe Sensitization by Nicotine on ThE the Vasoeonstrictor Response to Pressor Agents Lynnee Gray . T- and fdaZter M. Booker, Fed. Proc., Maeh, Z966. 3 EN! The Effect of Mephenternrine on Digitalis Induced Arrhytlz-mi,as. B. Bhagat, D: Sodhi and WaZter M. Booker, Arch. Int. de Pharn. et TTxer=p. VaZ'. Z6Z: Z, Z966. Acute Hypertension by Debuffering; the response to . Del Re; 47u Ant'ihypertensive Drugs in the Anesthetized Dogs. Lynne Gray (A1 and WaZter M. Booker, PharmacoZogist, JuZy; Z966. Fsa-ther Studies on the PossibZe Relationship Betrueen An_atiotensin and Norepinephrine at Sympathetic Neuroeffector Sites. RandaZZ Maxey, M. AZexander, R. EZZis and WaZter M. Booker, PharmacoZogist lA: 293, Z909. Th, Em Fe. To PossibZe Adaptation of the Myocardir.arr to Corona:y Artery Pa' Constriction. S.N. Dutta and HaZter M. Booker, Arch. Int. da Jo Pharm. et de Therap., Z970. Do The Effect of PropranoZoZ on the Carotid Sinus RefZex Response In A. Hyde and WaZter M. Booker, in Anesthetized and Conscious Dogs F.Z . Pharmacologist t2: 188, Z970. Ph Fc tiT I ~
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341 CAl"ECBOLAFITh`ES - GTJAT 'D. Sensitivity,of IsoZated Atria frcm Reserpine-Treated Rats to 1Vor-Adrer.aZine. B. Bhagat', Walter M. Booker and WilZiam L. West, Z964. Studiss on the Synthesis and Release of CatechoZamines in ., the Isolated Adrenal Gland of the Dog. Melvin Smith, Lawrsr.ee Brown and Walter M. Booker. Fed. Proe., Mcaeh, Z964. Further Studies on the Synthesis and ReZease of CatechoZamines in the IsoZated Adrenal GZand of the Dog. Melvtin Shrith, Lawrence Brown and Walter M. Booker. Fed. Proc., March, Z965. Further Studies on the Possible Central Action of Alpha Methyldapa. A. Fletcher and WaZter M. Booker. Pharmaeelogist Z2: 187, Z970. The Influence of Nicotine on the Synthesis of Norepinephrine. J. Stewm^t and Walter M. Booker. Piarmaco"aogist Z2: 468, Z970. 3. ENDOCRIf`E Depression of Thyroid Activity by SuZfonaraides; Tkyroid-Pcviareas ReZationship, (Abstract)' Fed. Proc., May, 1547. The Effect of ACTB and Cold Stress on Ascorbic Acci.d Metabolism. (Abstract) Fed. Proc., April, Z950. The Influence of AdrenocorrticaZ Extract on the Dayy To-Dad Ercretation of Ascorbic Acid in Dogs. (Abstxact). Fed. Proc., April, Z950. Tolerance tc Ascorbic Acid and Changes in Sertan CboZesteroZ in Patients Before and Daating Cortisone Therapy. (Abstract) Journal of PharmacoZogy and Experimental Therapeutics, ... Decenber, Z950. Influence of DCA, ACE and Cortisone on Blood Levels and Urinar-y, Eseretion of Ascorbic Acid. (Abstraet)'Americaas JournaZ'of Physiotogy, December, 1950. Factors InfZuencing the Survival Tiuare of AdrenaZectomized Mice - in Ccld Stress (Abstract) Amer. Jour. of Phys,. Dece.m3 er, Z95Z. :~ o ~~: Fbm 11 I 4
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342 EHDOapuw - co:vT T. Response of AdrenaZactomi,zed Rats to Pen*obcabitaZ Sodiun. (Abstract) Amer. Jour. of Phys., Decereber, 19st. EsperimcntaZ Studies on Ascorbic Acid Metabolism. Amer. Jour. of Phys., Auguat, 295Z. Influence of A,drenocorticaZ Eztmct, Cortisone and Desozy- Corticosterone on Blood Levels and Urtinaxy Excretion of Asmrbic Acid. Proceedings of the Society for Esperimental Biology and Medicine, Z95Z. The influence of Adrenocortical Estract, Cortisone and Desoxy- Corticosterone Acetate on the Blood Levels and Urinary,ESCretion of Ascorbic Arid. Proceedings Soc. Exp. BioZ. and Med., 78, Z95Z. Effect of Cortisone on Tolerance to Ascorbic Acid and Level of Blood Cholesterol in Man. J. Clin. Endvcrinol. and Metabolism, 12, Mzrch, Z952. Analysis of the Electrolyte Changes in Blood, Ur^:ne and Tissues During Cold Stress. (Abs tract) Fed. Proc., April, Z952. Iirtplications of Potentiatz•on of AdrenocorticaZ Hormone by Ascorbic Acid. (Abstract) Proc. Am. Scc. for Pharrnacology. Studie Whole The Ef Certai PaZL h 27se Di Uns tri and Di The Rd Fed. ] Recen- Clini4 May, T7te H Cold , PP• 4 The R Septe Influ Again Febru FurthPS Studies on the Implication of Potentiattion of puro, AdrenocorticaZ Hormone by Ascorbic Acid. (Abstract) Proict Fed. Proc., Mwch, Z953. ~ Inter-ReZati.enahips Between Changes in Adrenal Ascorbic Aci.d, 4. A1VES7 Electrolytes of Blood, Urine and Tissues and Corticoid Activity During Cold Stress (Abstract) Ibi.d: Obse2 The Influences of Testosterone on the Rats of Pentobarbi.taZ Anes- Anes. Metabolism. (Abstract) Ibid. Studies in Qrygen Consmnpttion of Liver Tissue of Intaet'and AdrenaZectonri.zed Mice. Fed. Proe., April', 1954. The Influence of Some Steroids an the Metabolism of PentobarbitaZ Sodium. 'Ibid. Inte: Fed. - Soee (Abs
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343 Studi.es on the Cs„vgen Cansumptioro of Liver Tissue and of JnoZa Bodies of Mice FoZZcjing Stress. Federation, Apri1, Z854. The Effects of Ascorbic Acid, Cortisone, GZutathione and Certain Enaymes of 0--ygen tlptake of Liver Ti.ssue of Rats. FaZZ'Meeting, American Society for PhasnacoZogy, September, Z954. The Distribution of CZ4 LabeZZed C'rtoZesteroZ'in Stressed and Unstressed Intact and AdrenaZectomized Mice; Turnover Rates and Distrributi.an in Dogs. Amer. Soe, for Facrm., September, Z954. The ReZation of Succinate to Adrenocortia2Z Function. --- Fed. Psbc., Z4: Z, Z955. Recent Advances and Concepts of Adreno-CorticnZ Fiasction with CZinicaZ Importance. Jour. of the N¢t'Z. MedicaZ Association, May, 1856, YoZ'. 48, No. 3, pp. Z59 - Z64. The ReZation of Ascorbic Acid to Adreno-Cortical Function During CoZd Stress. EndocrinoZogy, Ya1. 56, #4, ApriZ, Z955, pp. 413 - 4Z9. The ReZation of Suecinate to AdrenoeorttieaZ Fwsct'ion, Ertdocre.noZogy, September, 7956. InfZuence of N=atZy1-Nor-Morphine on RenaZ' CZearance; Antagonism Against Cortisone. .7. Pharm, 6 Exper. TheraF+eutics, Z29: Z34, February, Z957. Further Observations on the ReZction of Suceinate to Adreno-CortieaZ Function (with WiZLi;1m L. West)'. Fed. Proe. Z6: Z, N=ch, Z957. 4. "ANESTBESIA: Observations on the Carbohydrate Metabolism During ProZonged PentothaZ' Anesthesia in Dogs. The BZ'ood Sugar and the Liver GZyeogen. Aneatnesiology, JuZy, Z946. I Intermediary MetaboZisnr of Carbohydrates and Proteins. (Abstract) Fed. Proc., March, Z948. - Sane MetaboZia Factors InfLuencing, the Cou-se of Anesthesi.a. I (Abstract) Fed. Proc., Apri.Z, Z949. ©
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344 Changes in Blood Vohcne During, Prolonged PentothaZ - Anesthesia. (Abstract) Fed. Proc., April, Z949. Further Observations on the Effect of Prolonged ThiopentaZ Anesthesia on Metabolism of Carbohydrates and Proteins. Jour. of Phar.rr. and Exp. Ther., June, Z949. Studies on Renal Funetion in Various Stages of PentothaZ Anesthesia. (Abstract) Fed. Proc., April, Z950. Further Observations on the Effect of PentobarbitaZ on AdrenaZectomized Rats. (Abstract) Ibid. The Metabolism of PentobarbitaZ in AdrenaZeetomized Rats. (Abstract) Ibid. Some MetaboZic Factors Influencing the Course of ThiopentaZ Anesthesia in Dogs. Amer. Jour. Phys., Vol. 170, No. Z, July, Z952. S. CENERAL a. VITAbLT1V C EsperimentaZ Studies on Ascorbic Acid Metabolism (Abstract) Fed1 Proc., ApriZ, 1949. - CZiniail Studies on Vitarain C. (Abstract)' Fed. Proc., April, Z9:9. Implications of Ascorbic Acid Cholesterol Antagonism. (Abstract) Amer. Jour, of Phys., Decenber, Z950. Further Studies on the Antagonism Betveen Ascorbic Acid and Cholesterol. (Abstract)~Fed, Proc., April, 195Z The Relation of Glutathione to Ascorbic Acid in Adrenoeortieal Funetion. Proc. Intern. PhysioZ. Congress,•Canada, Z953. The Effects of Ascorbi,c Acid and of Cortisone on Heart MuseZe. PalZ Meetirng, Amer. Soc. for Pharm., September, Z954. ReZationship Betweer. Clutathion and Ascorbic Acid in Adreno- Cortical Function. 4'he Amer. Jour, of Phys., Vol. Z8Z, 9: 2, M¢y,, Z955. b. Re-E Fed. The Anes Anal Re-E Agen Thar Prim 1qsy, d. The ; Acca of M Laba. Influence of Ascorbic Acid on the Dis tribution of CZ¢ Labelled Cholesterol. Ibid.
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345 b. DRUC E7ALAATION. Re-EvaZuation of Metra.zoZ as an Analeptic Agent. (Abstiexct) Fed. Pnmc., Marcic, Z948. The Effect of OnetkyZ on Respiration and on Blood Pressure in Anesthetized Dogs. Current Researches in Anesthesia and AnaZgesia, Mazj - June, Z949. Re-Evaluation of the Effectiveness of MetrazoZ as an Analeptic Agent in Barbiturate Depression. Josr, of Pharm. and E.,-p. Ther., ApriZ, Z950. c, PATH©IACY Primary Carcinoma of the Liver in a Dog. Archives of PathoZogy, May, Z948. d. 'TEACHIfiG METHODS The Project Method as a Laboratory Teaching Technique During the AccaZerated MedioaZ Program. Journal of the American Association of Medical Colleges, Novea+ber, Z944. Laboratory Teaching of Tozi.coZogy, JAAM, 28: 4, Z953.
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