Document J3L19wp8EB6bNr1p6bXa2M4VB

'l l u ^ y a . ] PLAINTIFF'S The gTew England tore XKI3IT # |foumal of Medicinei formahoi ERRHStaUkha* uuuutte raw araura jocuax. or rameira m nraour VOLUME3M Original Articles Faauiy Kanagaaanc in tba Pnawaion af Eaacarbarioaa of Sehaophrsnki A Coacrotlad Study...................................... I. R. H. Fauooo. J. L Bon. C. W. MoColu J. Bacam, H. B. Mon, am A M. CtuwtMA* Tfca hnnnlwi of Alpha Thilawamia and Hoamffoiu SickU-Coll Diaawa.......... 0. R. Hiaoa, I. E. Auaieaa.j. Lam,J. I. Cum. D. J. Wcathuau. R. J. Hato, Y. CtAjcaneo. Y. Lame. K. 7. Maooo. S. E. SuKAJfT, Ajro C. R. Sujtur Medical Prognss Tha P>ii|iom'i of Aabanoa Awwinrad J. I Caahwaao am B. T. Manoio JUNE 17. 19a Editor^ M Albatoo and Hnuo Umh, I M. L IlfBAil NUMBER 24 1441 Soonding Boards Aftv Laatrfla. Wkaaf...................................... XXCAWin A Fuan Skaraga of Raatdaney Training Paaidaam Dflaanaa or Opporouuty?... 0. A Kama am S. C. Oonun I4tt 1444 '.Correspondence 144S I af OfWkaJoda Tlwolal. Medical Intelligence Dm TSwapjrx Alonolot and Tlaaalnl. Too Now Syaaala 0 Adranaaafiw Aatagoaiats................................................ W. H. 7> 14M Dlaraniam Cottiaol Ratponaa Eiaganm'iii 2X7!ACXH and Iaaalia.Iaducad yawinjn Patirata PUauCary Diana*. G. C liar. H. J. Moanaao, AM J. T. O-laiAB 14a Inararantriealar Uaaaorrhapa in ike Prawamn fnPiati A Oianafaa Outlook...................................................... S. liani ia. R. A Vanaa. K. Oaamin, A J. trSawA, J. Auw, amJ. M. haaw HMni^|o(t QgMriM Uaiaw Ltahacytm Eapaatd is Cjradaa Diwatkyl Eaaar........................... R. Iiwanaa. P. IWn, T. Tunc, A llnint W. A Can, amJ. IX tnaauna I4S4 14(1 i Recorda of the MeseechusetU General Hospital AII>Ysnr-OM Waaaa arkk Ckrwric Askan and IlaaaofMyia...................... 147! N. U. fcAAunr am K. J. Maos Paadhla_AlWariaa of Maeaaidawla Hmhidliw Cm* SanaMi mA Cmmm.......... . KteW Am tmm* Kaiffct mm Ummltf ftaaMiil I --f-Tt-- Cm . 1 UMUai AS^mkkm fcr TkM kru I Cm Irak Raricwi. tfi Special Report Tka Madatar Madkal lawgrawd Carrkalawt Aa laaaaatlaw in Kadiaal lAacaomi.......................... AJ. Cumt, E. H. Imam. amJ. L lu 1i44s9e4 1499 14*1 tot 14 14ft 1499 14*4 1499 1499 I4M 1499 ISSt IMt TnNarW iAPiAiiAiAAMac.a)Haua. waatf mi ramiASTUbt UAHIIA - .UAWtlM. NBJMAQ 308(24) 1437.1904 (1992)' <WT> jf t t W t y P - 'i -- J .V v; ' - C' 1;' DU 037588 140 THE SEW ENGLAND JOURNAL Of MEDICINE Jum 17, 1912 The New-Engiand Journal of Medicine exposure to asbestos and HUMAN DISEASE _ OfcWOnproC *-- Ms--win-- Madinl Mr Duxo the put two decades, ill health malting front exposure to asbestos hu been the subject of in* Fwvy W, W--nua. ALU. tensive observation and reaeareh1 -- probably more inteaiive thtus research on any other environmental WUIaai E Miur, M.D. fa-- Km Karyi--k-- Charles S. Ammvtmm. Jr. atent.2 In the most direct target organ, the lung, and in ia pleural covering!, there it a wide ipectrure of rcaponte after exposure; not only acute and chronic i ft'v his Whut ar tvs Caaamti am Pwotim inflammatory diacmaoa bat alao cancer of there organa ortua Mmnawm Msatau. Socixtt may occur. Research hu bees stimulated by the belief l Jaa-- T. ilcDaaauf*. M.O. rUirmmt that the more complete our understanding of the Jaka t. Saw*--, M.O. Join C Aviso. M.O. meehaniama of pathogen--, the better will be our WUSaat H. S--. M.O.. D-St Wiliam >. Mmwa 11.0. ability to control the continued ure of this mineral in Fraal E. SJshr, Jr, MJX Sum K. S--mt. 1L0. today's complex technologic world.1 Arnold S. tefinaa, M.D. Eamn Mania Aagrl. 1LD. Dtrtrrv Canoe Uia W. Salamaa. M.D. Oaavnr Canes Aa--aura Earn-- The review by Craighead and Moumart of the pathogenesis of ubestot-related diseases in this issue of the Jmami* which covers recent work in cdl biol ogy, is act in the contest ofpathology but also discusses the use of there minerals and regulatory consider Ja-- r. Dnftrgw. M.D. Nana-- K. 1L0, n>.a la--M A. Mali. MJ>. Man-- N. Swans. MJJ. Frankie H. Epanie, 1L0. ations; it complements other recent reviews of the epiocmioiogy of there diseases,1 their impact on poblie health,* and current clinical issues.' Also important is Fraw* 0. Users. AID, Ihi JUvmw Earn-- Jake C. Mar. 111. SLD, Sransness. Canmw a recent repert that provides criteria for grading the pathologic changes in the lungs associated with ashes- JaapkJ, Ha, lr, Maaaaaa a* Can--tat. Pan in--i ta--f t la-- Aa--rant Can-- tea exposure.* Systemaiiation of paihoiegteal sue--menu can only enhance the pooling ofexperience from Mill-- A. Ttarar. Earnout. Oma Man-- dificrent cental or countries by maximising the com parability ofstudies. The international diniAcatiau of radiographs of pneumoconiosis' by the International Ekhart H. Eqkslk. 1LD. _ Fsal Pikk--i. 1UX BufcGtnM. MJX Jawph a. Uaaaa. MJJ. RafcmJ. Msysr. 1LD. rradanck N'lkslie. ltd Aiwa V. Outiya, 1U1 J--a T. Unlit--an. M.O. Ha-- Kaaa--. ltd Katumk Meta-- MO. Kan--* J. EfXbmaa. Dr.F.H. DtvdG.Nttkan.MJl Kan J. Back. M.O. LawsseeaG. la--, MJX J.aaa.lUX Labour Office is to example ofsuch systematization, and the dividends asocialad with its use are generally recognised. Perhaps the major contribution of the review by Craighead and Moismin (and this may surprise read er! not familiar with the field) is the emphasis placed on the shortcomings of our present knowledge of the Jake K. Ickkarc. Saaau. Caaaamiimcirr FrakaHck las--. Ill, Ocaasna -- I--can Oacaana-- t--M IL l--a, Maaaaaa -- A--aan--a * Miaaaran Wllaa H. hip. Itaaaaaa -- Fai--icnna * 0--aiaunaci ' Mil-- C. hint, Jr, Co--otrstrr pathogen--is of aibestas-rciated disease. Considering lint the (ate of inhaled fibers in the lung, it is now evident that the dust burden ofthe lung is primarily in the form of unrooted asbestos panicles/ whether or not these conform to the definition of a fiber (i.e., a partide with a length-to-width ratio of 3:1). This defi nition probably originated rather arbitrarily Crum a need to standardise what area considered a fiber for -- a-- at---- aaa --a p-- purposes of mdusirial hygiene*; it is now widely be lieved that a much higher ratio, perhaps 10:1, would have bees a better choice. Both fiber length1* and I Manana t-- atananV-- EghadJ--ItfJMBah --niik napikia TW>--tt tietnS-- mafia--iniHikr--r--iaiaW mineraiogic type11 are important determinants of whether a fiber becomes coated and to takes oa the Suniliar appearance of the asbestos body. Moat aabso- tea bodies found In humaa htftgt contain an ampbibola ____ UCM CKman I Iff* Ml pr--mean-- wekrua IB |-- wan ---- SB ym --A G--aka <VA k--a aaMt IB -- war (la-- nkkn-- Ml pap-- --k--a SB -- wad. Mel cknta w *-------- ft---- 9XX --a 4772. I--on. MA OBIS. ........... rlniaii laciaa il la. Os-- MV StMl I--a-- --slana--sno 1--aa-- 11 ri Gaaa'iiaiu i-- la--a. MABIB. fiber as a core,11 exes though ehryiotile accounts far the gteatCK use sad prcam--bly the most exposure.' What permui tonre pardcki m lie apparently donna- in the lungs for loag periods before evoking aa organ response is not known, and there it no good explana tion for the fact that ail the disease consequent to --bassos cap--are (including fibrous of the lungs and mmermwa DU 037589 <fiJliatteV -1---Agi-.-?*& tar. VdW KfcH EOITOXIAI. IOI pleura m well u cancer of 'hoc orgins) may appear long after exposure hat ceased. Fibrosa of the lung (aabcuosuT waa recognised by . the Brat decade ofthia eemury and hat been the subject of much research in animal models. Xcvcnheiest, Craighead and Moaaman conclude that the patho genesis of aabestoaia remains to be established,* as does the importance of exposure dote aa compared with individual "susceptibility" in the initiation and the progression of the fibratic reaction. The finding of aa acute inflammatory response in some early human lesions* raises the issue of whether there is a reversible component to the acute response in human beings, aa suggested by work in animals.11 Long-term studies in sheep11 may help to answer this question. As (or whether asbestos acts as an initiator or u a promoter of lung cancer, the authors of the review* favor the Utter view; perhaps particles act aa physical carriers of other environmental carcinogens to the basal epithe lial cells. It is also possible that more than one meehntiiam is involved.' There is perhaps even more uncertainty about the pathogenesis of pleural reactions than there is about parenchymal lesions. For instance, it ia not dear how often acute exudative reactions, uch is effusions (pre sumably usually clinically silent), precede the more chronic diffuse or localised fibratic reactionrofvisceral or parietal pleura. It is also unclear how fibers reach the perietal pleura aad concentrate there in suds a way sa to evoke plaque production after a long delay while leaving the visceral pleura intact; an adequate hypothsais Car the pathegenssts ofpleural plaques js needed us explain all these features.'* Perhaps even more pes tling is what determines whether the pleural reaction will be benign or malignant. Not ail would agree with the view expressed in the snick* that maiigruat mesotheliomas are pathognomonic of asbaios caposure: these tumors were described by European pa thologists in the 19th century -- long bcibse major commercial exploration of the ubestos minerals11 -- and there it little evidence even today that asbestos ia responsible for many eases in men or women outside industrial centers.3-11 What are described in the pres ent review as "casual** exposures (i usually domes tic or neighborhood) are exposures that are intenektent but have often runted out to be to very heavy dual douds of line particles.1 In spite of considerable current interest ia the topic.' the issue ofwhether asbestos exposure is ssseei ated with airway abnormalities ia not addremd by Craighead and Mossmsn. The imuls-cmcat of small airways in the cariy stages of aabeatos-reiaicd lung ftbrain has in aU lifccfihuod its clinical counterpart,' although there ia no evidence about w hether these abmmaiHrirt are reveraiidr nr not. The assuesatiae be tween asbestos exposure and miser forma uf airway response, such as bronchitis nr emphysema ia rhe ll> ( of aabrstosk- also remains u> br clarified, aa do the confounding rileets of cigarette smoking. Finally, there is (be question uf whether liter* are diflerenees in the pathogenic potential of the various-fibers m this mineral group. Of particular ootieun is -whether chrysotUc (which has accounted for over 90 ' . per cent of commercial uses during the past teverxi. decades) differs from the two amphibok fibers, croeid- elite and amosiie. which were used extensively during World War 11 aad in the postwar building boom. The tissue has been bedeviled by problems of comparing . bke with like,5 by the difHcuity of toning out the rda- rive contributions of exposure (duration, level, and .parade size) and fiber type, and by the differences between exposure in the mining and milling of fiber and the secondary application of fibers in manufactur ing. Thus, although it is clearthat the rates ofmesothe lioma are different in different exposed populations, it has usually not been ponbla to assess the extent to which these differences are due to fiber type or to otitcr factors- Same darifiestkn has come from the applica tion ofmodern methods oflung-dust analysis to autop sy material. In two easc-oottirei studies of mesothdioma. an excess of imphiboles (tmosite ia North America aad aoddolitc in the United Kingdom) was found in the lungs of the cases, whereas chryaotiie contents were similar in eases and controls.u* In a study of chrysook miners in Quebec, almost as much iremoiite (an atnphibok eomaminadng some of the mitred rock deposits) was found In the lungs aachrysodie, although the latter was dearly the main environmental contaminant.'' There results are consistent with what has long been believed on the basis of more tenuous evidence -- that there it preferential dear* am ofdwysodlc. as eomparad with amphlbuic fibers, from body **---- aad that this may contribute to the differences in the patfaegenk potential of the minerals^ Epukmioiofk evidence for a fiber gradient in pathogenic potential ia strongest for mesothelioma. with eroddoiite more strongly implicated than citryrodie, and atsaosite probably in between- The evidence is also reasonably sueng for lung cancer, with erecidolite agmia more strongly implicated than chrysotile. Par pleural reactions (pleural plaques and fibrosis), there may also be a fiber gradient, although other factors are almost ocrtatriiy involved; fire parenchymal fibrosis the evidence for a fiber gradient is minimal. At proent it dr believed that the biologic activity ofasbestos pprtides relates so the degree ot penetration and the amount of deposition in the lower respiratory tract, both ofwhich depend xreialy on their physical ehataeterittks. in cluding their acrodynamk properties. Parttek sis* (aad particularly length and fineness) may alio deter mine oneogenkity. However, biologic activity is likely to be modified by the leHgth of time that partieki survive ia the lung without denaturing, which may be related to their chemical characteristic*. The mast plausible explanation lor diflvimeos in the pathngmk uf various fibers ia that these differences re sult from differences ia bush the physical and chemical propsxtka of the filters. What la the clinical ini|xmaacc of the issues rarsrd by the review in tltcjkmrefl Perhaps the moat impor- I 0936365 DU 037590 1443 THE NEW ENGLAND JOUtXM.itOJCI.\E taai it (hat health risk* in aiarion to exposure ia sibes- to* vary according to environmental factor*. Some of thete factor* (such at exposure dote, particle site, and fiber type) are known, but there are undoubtedly oth er* ool yet recognized. Hoot efiarieternises probably aiao influence the response to exposure. Thus, in contidering the individual patient with a disease known to be related to asbestos exposure, the wise dinieiaa should avoid regarding any particular exposure as tooshort, coo remote, or at too low a level (eves ifenviron- mental counts were in compliance with the present regulations) to have accounted for the diaetac. Assess ment of the importance of particular environmental exposures is often outside the diniaan't expertise; it should be referred to appropriate consultanta in indus trial hygiene, engineering, or physics. In lung cancer the stadsdcal probability that a given ease is attribut able to asbestos exposure may be estimated from expo jure-response data,'* which far priedcal purposes can probably be assumed to be linear, provided that the data available are applicable to the industry in which the subjact was employed. Finally, the unpredictable clinical course of these diseases demands vigilance by the clinician with respect to past exposures, and the mow powerful indicator remains the careful, complete, and predie occupational history.' Whether the dust oonceatnuions pemrined by cur rent regulations will ia fact dhaiaaie the future risk of asbetmair, as Craighead and Mossaan suggest,* re mains to be established. Similar suggesdoos ia the 1930s moved to be premature. Evaluation of the im pact of present oantroii oa health issues is an orgeat amtttr me rnssrHi Furthermore, a total ban on use annas uniiludy ia technologic wottiti,1 ia which it may be considered preferable to retain diets verntik minerals far certain uses. Until it is established that asbestos substitutes do not carry health risks,1' re search into the "***"'", by which isbcctos parti- dee produce ill health should be vigorously pursued. ftfaCH IMm% Mvanls PQ KlA Xft4 CMUM MsMSMt R. BgCSUAU, MJJ. ,, *"" SOW n an IMS Ire! tr/hSMaL ttSkiTJMT*1 <> Cass AIf. Sans _ .1 md mtm Snw Anite " IA OM. b| __ tr I fa* Ma*. iftl: ** ft. Wipna M. MmS.tf. 4 *riaM*M*iMd*a 14. Hll U. JC. Mrflnill AD, IplluMliB mm MM. Pm M*. IfH; fcCW*4- I*, ilrfdads SO. McOia<<C.^dwW. MlsHtwsntdns Ism la naaMdd maan a Hmm > aa a. sas Oaan Mss. in areas -IT. retire K OMs ow. MareaaM so Airerea ares a re are, w "Satan-- -ralal aIjreax.ua.OatasHas.<n II tarefltem. AenSanfeCfer d na dat at aarerean. dan itex re Jwd tAasansJJM. isttn-ML """en'waae* unsadi ~ Ureirere SOUNDING BOARDS AITBM. LAETWLE, WHAT? Laetulx ws* moribund befisre Mosrtd et ai. laid it to rest with the rtetnt repoet of their proapcgive dialcal trial.1** It had been replaced ia popularity by so approach unusual ia the amsiit of unorthodox cancer therapy--one that rcprsssaa mere of a challenge than did Laetrile or ia predecaamcs. This is the `natu ral" approach m malignant disease, which emphasizes cure through punfleaooa and the body's capacity to heal iaetf. The cuneatly papniar aiwrnailv* apnrsnch ia rooted ia hoaeopatUe and naturopathic beliefs, Indian and Oriental philosophy, and 19th-etnrery theories of intestinal putrefaction. Promoters alien evoke the rime-worn conspiracy dogma, which tates that the medical system, the Food and Drug Adminis tration, sod the federal government withhold true cates from the public, thereby perpetuating therepeurieally usdeel tad biologically harmful eaaear treat ments ia order to farther the Eirablithmeat's aooaaota ic interesta.1-* Alternative eanctr therapist ia vogue today differ importantly from Laetrile and from other uaproved remedies of the past. Previoas unorthodox treaemma were "medicines" or t( least "recdidasl" F.ssmpiee were Or. Bye's ComWaation Oil Cure, Or. Chamiee's remedy far removing cancer virtues from the blood. Dr. Leach's Caacmi, Or. Koch's gtyosyiide, sad maajr others that attained great prominence in their day.* They came in ampnlo, viala, or syringes, mim icking standard msdlcatioaB; tad they were raid and administered ia the usual critical f-->*i-- by people ia white coats. Today's alternative remedies explicitly reject sasoriarion with standard treatments, eavitoomeau, and paraphernalia. Them are aati-medidacs, eraphaaixing pnrifirsnon through dietary regimens, dttoxificatiaa 99E9E60 dfld DU 037591