Document MZw8Yw2w0G2zNGbBd6k9VZXz

FILE NAME: ZW^W^ DATE: EZ DOC#: W^ DOCUMENT DESCRIPTIONW:Z I H, ll 1 .1rt. :'.>f :i1!!l . r,. :L.,: f"!'. .. !1 . Case Reports _-\.s1Jestosis ~nd Btonchogenic Carcinon1a* R!jirJJi :!( One Autojx,ied Case and Review of the Available Literature K:.=_;- J. Js:;EI B.\CHE1~, M.o., H.\1''.\'A Ku,cs, ~1.n. and HARKmT L. H.\RDY, ~1.0. Boston, Jfassachusdts r 4:1r ;~== a:, in -'.:i-~il a L~ a-..,:Jal:,k St'\ t'ral reasuns for prL",cnting c~sc report and~ re\ic~\' of the luer.1turc dcalmg with tlw curtains and clothing. The chief operations arc di,integration of the crude mineral, carding the fil>cr, ~cparating the more mcful long from the ::'.:,1:~:1s::i::, h.>twcc-n occupational l:--.posurc to . - ,:,:os ~,:-.d respir.itory tract nwli_;nancy. The short fiber, spinning, plaiting an<l \\ea,ing the :ish('stos, often \\'ith cotton. Insul;:ting matnial .;.i;).::-tnt ::1erc-asc in hronchogcnic carcinoma, -;, . .i:,;:: i:1 1:.?.ks, reported in the pa.,t dcc,idc ..,~ ;._.a , ) 0 .:-ruriny of rcspirabk dusts as pos~ilik ::,,).,c-Y >1u;:: r.nglish ol>sentTS1- 3 arc ~atb!ied : :-: iL. :, i;: a statistically signific-,,nt incrc;.?sc- is prodt1ced by mixing magnesia, diatomac:nms earth and other materials ,,ith asbestos to m~1ke cements or fillings for in;u\ating boilers, engines ancl pipes. Other nun-le:-til<.' asl><.'stu.:; products so made inclu<lc a~bcstus Celllcnt, sheets, brake : ul:::.:1:iry rnalign;1ncy among aslystus .:;.;,-r,. '-,n:, ..\mC'rican "ritcrs con!->idu that , ,p,:icncc 10 datL' docs n:,t ~upport this . ::c:.1i,-... 1 = Tl,.: \\ork ofGraham,fi,; Doll and ;rn<l dutch linings, ehctrocks and S\\'itchboard panels. .-\slicsto[ is a h: d1 atLd magn<"~ium silicate. The chil'f supplies arc in Canada, Cape Pro,i11cc-, :~_;:_' an:: Och,nc1 .ir, ha, crcatcd much intcicst :: t:,,.' CCirclation of ci:,:;ardtc- s1:ioJ..ing \\ith Italy, Rl1ocksia and R.u,sia. Asbestos dust gi,en off in manufoct uring pi ocesscs consists of ira~- ._,::cLo,,:,11ic carcinoma. E. R., ,\hose- case is mcnts of fibers and small rounded or angular . :c;r, :rt'~cmcd, was C')..posed to }urmful particles. Actual studies in industry show the -: .-.,: :,,'r. :.,:,.::i.~ of ~:~lxstos dust and \\'as a chain This p10,..-icles speculation as to the >.'f,;:)k r...,le of two etiologic agents. F c,, r,-~1orkd c:>.ses of lung cancer rd,itcd to sizt and shape of the particks of ;.ishcstos to lie such as may gain cntran<:C' into the b.-onchiuks. ll E:--pt-ricncc- has led to the acceptance of fi\'{: million particles of asbestos per'cu 11ic foot of air, .:::it.:':ri.:d ashe"stos exposures prm ide cbtd on ._::, c:~:,,r:1ntT ,md quantity of dust <"XJK'Stire. of smcill enough size to be respir:ihle, to Le the s::ifc \\'orking concentration . ::::,- !5 a :;.,rious ddicit in exact stud: of etiologic Some operations lwc.iuse of their du!--ti:1css . -,;,e':;;ic,a. In the clinical report p1c~('nted arc more h,11.ardous than othcrn in :1sbt".,tos :,~in S1c:.tc authorities have dl"lcrminecl h, manuf.:lcturing. Bagging the asl1cstos, separating t::,-urc,:,cnt that the asl)('stos dust c:--pos.,r(' : ::-.i.- m:; n during his t\\ ch-c years of \\'Ork \\'as the Ion~ frum the short filJcrs, carding, spinning and "ca, in~ sho\\ a greater stat i~tical c,idlnce : .:::;.id<",,1hly ahO\-c- the safe lc,cl, which i<; con- of asbcstmi~ than du other opcratiom. .-\s might <::t':("d to he fi\e million particles per cubic _. -:,, of ::-, i, for ::in c-igh l-huur worki1._'.' day. lie e:--pcct<'cl, the longer the duratiun of exposure the greater the number of cases. In the hkrc- It i;; p(!'tinent to this prei-rntati,. that there "ether and Price ~cries then: \\'as one case under .. :-c prob:i bly a bout 10,000 worker., 1 ngagc:-d in :,.,:-~n1i:1!ly hazardous asbestos manufrtcturing four years'. exposure, and up to 53.6 per: cent with fifteen to nineteen years' exposure. 1& . ~,-:::nions in the United Statc-s. 11 :t-.fiddkton :-;-:;-is the nrnnbc-r in Great Britain as between _: _.-. ,1 to :i.000. 1' :--lost of the industry is engaged C\SE Rl:PORT .. R. (J\,IGH #735586), Ha forty-one year old 3~:x:~1os textile manufacturing producing asbestos mill \\'Orker, cntcnd the 1-L-1.ssachusctts :-:,c.:bting 111:-ittnsscs, !wake linings, fire proof G~ncral Hospital in April, 1951. The chief =l Fr,,m ,h<' Department~ of :l-,kdicinc.- and P.ithology, and the Occup:itional Medical Clinic, Mass:1chusclls G<Cncral :,;.?:tal, Beston, 1\lass. This work w;,s supported in part by the: ::--.a1ional lm1itntcs of H~alth, Di"ision of Rc;arch ......~ _....... ' : ,.- L ~I 'i' ,. R , 1 9 :> 3 721 .i C Asl>cstosis, Bronchogcnic Carcino1na-- Issrlliachcr ct al. tions 30, and temperature 99F. urally. Hb chest was thin and shmH'd poor expansion. Thrre were dullness and reduced breath ~ounds at both lung bases \\ith sticky inspiratory cr.icklin~ mies m-er the region of the left Iowa lol;c. Tlic lc-f1 l;orckr of c:a1 di.ic dullness was 10 c111. to the TAllLE I l'l'UfO);AR\' Fl"\C.l lu~ ~Tl.'.DI~. * !<LFuRL -"'D .\Fll:R ACTH t &fo1c AC'l II .\f1rr ACTJI .\1Jpro"<imate l'\rn 111al \'al111.~!,l11 -, trI ____ : - ,:, - l=',...:....;.;.~ .,_ -~ -...! : ..,. Fw. 1. X-rar or clwst. The lo\\'cr lolws ,ire rcduc ed in size and s!,:,w a "homyc omb" p.1ttcrn. Tht1 c i~ an inn c,,sc i,l linca, and nudul.tr marking,. .-\ den,ity is scrn in Ill(: region of the lingula with cnL11 gnnent of lymph nnd<'s in tl,c left lung I oot, suggc,ting; a tumor in that a, ra. complaint was prugrcssiH' low hack pain "hi<h had been present for four months a1Jd was only partially I dieYcd b) aspirin. In aclclition, onemonth before admis~ion the- patin1t noticed incrc-asing dyspnea on c-xcrtion, a \\'Orsrning of his chronic producti\-c cough, night sweats, anorexia, fLTcrishness and a 10-pound ,,-eight loss. He had worked in an asbestos mill for about twelve yc-ars but had stopped working there fur t,,o yc-ars prior tu this hospital admission. In the mill he had s1wnt one year in the "picker mom" whcrc crushing, grinding and wrting of long aslJC'stos fibt'rs was carried out. He also worked Jl\e ) cars in the carding room where the concentration of fibers had been determined b7 authorities to be considerably al1uve the safe lt'vc-1. He used one can of muff and smoked on an average of one to two packs of cigarettes daily for many' years. For se\'Cn or eight years he had Leen aware of clubbing of his fingers; <me flight dy~pnca was present for about two years. There had been no hcmoptysis. Physical examination re\'caln.l a chronically ill and <lyspneic man "ith c,id1.:nce of weight loss nnd cynnosis of the lips and nail beds. The blood pressure was 110/7 5, pulse 96, rcspira- \"1:.,l <ap.t1(ity (L.) .. ......... ..... ' ~la,imum Ln:-:i.1hl11g ( .Jp.1.< it> (L /i:-iin.) ...... Rt<;iduaJ \Oln111(' (L.) .. J:ITt"Cti" ~ ah t"d..ir \ tnti!a tion .. (!../min) ... Ah.c-ol.r pO: (mm Ilg\ ,\1h11.il pO~ (nun H~) ... :: ., .. ... j Ar:e,ia! pCO: (mm fig) ... .\11ni.tf Ot ~.:nuratiun (:) ...... Sc1um pH ......... .\1'tol,1:-1r1tri.:1I 0: drif~? nee (n,m Ilg) ., .. 2 4 5:! 5 I :>75 7 63 115 0 88 0 3(, 0 97 3 7 45 27. I 2 .18 3 9 79 l 5 49 I 10, I \(l 5 48 105 0 76.0 42.0 94 4 7 42 s O! 105 JO~ 95-97 40-43 95.97 7 39 29. 10. 1 hc,e <1u-::lit, ht1t Jlt"li, 111nl h~ D1 John .\ncldt, IJtpJrtnw11L of Ph~--in!o-:~. JIJr\:nd ~.. h,,nl or Pulil,l Hc<1lth t -\(:'Jll 100111~ i11u:irn11,luLul} fur 1ru<la~s ! B!JC~ "Ur'"(, a IC"a ,\ ,t" 1.62 ,;<i ,n. left of dw rnidst(-rnal line in the fifth intn~p:1ce; th('rc were occasional extra S) stoics; P2 was greater than .-\~; there was some pulsus p:Jradoxus. Li, er and spleen ,, ere not felt. There \\'as tc nd<:rne!>s of the spine OHT L-4 with sp.1sm of the lumbar musculature. He had extreme clubbing uf fingvrs and toes. Laboratory data rcvcakd a normal urinalysis. Hemoglobin \\ilS 14.0 gm. per cent and the white count \\as 5,700, with a normal differential. Chest x-ray re,-eakd the lo\\'er lobes rcduccd in size and s!io,, ing a honeycomb p;Htt.:rn. (fig. 1.) There appt,l!",d to be a hum, ,gcnous density in thC' lingula \\'ith cnLugemcnt of lymph nodes in the left lung 10ot sugg,-sting a tumor in the region of the left lo\,Tr lube. Films of. the spine indicated areas of incrca~cd and decrcasl'd density in the fourth lumbar \Trtc!Jra gi\'ing the appearance of melastatic mali.;nancy. Electrocardiogram showed nun-specific T wa,e changes. Non-protein nilrogen was 27 mg. per cent, CO 2 29.4 mEq./L., alkaline pho~phatase 4.9 Rodansky units. Repeated c-.xaminations of the sputum were negative for acid-fast organism,, asbestosis bodies and malignant cells. Two bronchoscopics re\cakd obstruction of the left lo\\'er lobe bronchus. The patient was giYcn a trial of ..\CTH 100 mg. dail}' intramusculti.rlr A ~I le: R I c.; A N J OU R N A L OF ~I E D I (; I :S I: _.,,. .... ------ ) t t \ ft,r tt'I c:-.cq>t ('.JI di,ll ! ,vfore i ,j SI I jf.C f1 ,:,thett l l ( l t i t t I I l .\ i>iJfO' norn Bcfu1e AC'l l .-\ftc, f :\Cl l''-l'IL .ind ::pp: BtI r;-idi,! 1l'licf Fo ,l'l'lll "ork ::ml l\\"U of 1Cl 30 J 1110d \'CJ'~ insp: the I huh' .I tact; l"hcout 11111( <lo,\ Asbcsto~is, Broncl1ogcnic Carcinoma---/11rl/1rl(hrr cl nl. 1,,i ten clays. Clinically tlwn was no change , :-.c cpt for euphoria. Pulmonary fl;nrtion and r,1rdiac cathetc-rization studies \,-<Te performed 1,tfurc and after AC:TIJ and likewise showed no ,i!.!llificant c!.ang<:s. (Tables i- and 11.) Cardiac c;:theterization did rc-n,tl chronic cor pulmon:1lc bloo<l count \\"li~ G,:i00, hnnoglol,in 11.S gm. pt:r cent. It \,as liditTed that tlw p,1ticnt had pnrn- monitis in thc right lower lolJc ;rnd early ror pulmonr1lc with eon:,.::-sti,e failure. l-k was digitalized, gi, en mercurial diuretics, anti- :- .. TABLE JI C.\ROl:\C CATHI-:1 t:RIZ.-\'I 10-.: STtmn-:s * Bl:roRE ,\-.;n ,\ FTER .-\CTH t -~! c.,.,<: J . C..on,Oum, pt1.on,1 2 .t. J p..l~1 I> I (cc./min./ ~q in.) la, ia :\rt cry (cc./100 cc. ) O, Content Radial Artery ( cc. / 100 cc. ) I 0: . Sat11ra, tion Radial ;, A(r<t:n7 -)Y. I /t ! i ' Pulmon,u->-' 1 fran I I .\1 tcrv P11lmona1yl : P1csu~e :\rtery : Pn-~sun . (mm. l lg) - . ( mm. Hg ) I 1 C:.-11 diac lnd..-x (L./min./ sq. m.) - - - - - - - - ~ - - - - - - - - - _________1________ !____ ! - - - - - - ------ --- -- ------ ----- \ l'l ,roxin,att' nonnaI va1ucs 3 '' 145 ! fl, fore { Rest. ....... 1!!0 .\(:TH l\lild cxc,ci~<'" 1 (2 min.) .. 370 .\f1cr { Rt'st. ...... ,I 1S6 .\CTJI .1\f1l<l exercise (2 min.) .. : 349 I 20.0 19.0 96 30/10 15 3.2 19.3 18.1 94 36/14 21 4.47 43/14 28 5.55 17.4 16.6 9$ 38/15 23 4 02 52/22 36 6 97 These ,tudies We're p:rfnnn..d by the Cardiac Cathcterization l'nit of 11,c '.\!..;,achusl'lts Ccnn~l Hospital- t 11,duding Dr~. G. S. '.\fycn ..\. L. fritd!ich, .I. R. o:,.;:cill, G. e,_,hen and J G. Sc-.mnell. :\Gl H 1O(J mg. intnunu:-c11la1 ly for trn days. \\ ith slight pulmonary h) pertcnsion; after l~.crcisc the pulmonary hypert,nsiun incrca~cd a11d significant arterial oxygen unsaturation app<ared. Before discharge from the hospital he rccei\-cd radiation (1,200 r) to th<' lumbar sinc \\'ith no rdicf of the hack p:.-tin. For several weeks aft<'r discharge- the patient .,eemed somewh;it bcttu and rcltlrncd to li~ht work. I lO\\TVei-, th<.' cough innc,-:s-:cl markedly and he h.-1d se"vcre dyspnca at rest i;o that after two months he had to lx: n-admittc:d. Physical exa1nina:io11 on re-entry rr\cakcl a temperature ofl00.4"1.-. rectally, puJ--;cof120-1-'!4, respirations 30 pl'r minute. I-fr had m:i1kcd tachypnea, moderate cyanosis and such d) spnea that it was \"cry dif1icult for him to speak. There were m.iny i11spiratory and c-xpiratory wheezes throughout the lung ficlcls. At th<' right base there were moist bubbling ralcs togc-ther with dullness, reduced tactile frcrnitus and increased \'ocal fremitus. The- left border of cardinc dullness now extended out 12 cm. from the midstcrnal line. P2 was much lu11<kr than A 2 The liver was percussed down two and a half fingcrbreadths and there was 2 plus ankk ecltma. At this time the white N O \" }: ~I II J;. R , 1 I) 5 3 biotics (penicillin and streptomycin), and \\"3S in an O:-.)_tr<n tent rnost of the tim<'. Chest x-rays no,, \\ ere su~:i.:c~ti\c of 1) rnplia tic sprc"d of tumor. In spite of all therapeutic m,a_c.urcs frvn, <lyspnc-a and c:-,rnosis grc-w worse. He became confused and diccl on the thirt) fuu1 th hospital day. At necropsy the p:iticnt wr1s cm,Kiated; the thorax wao; lcngthenC'd in the antc-roposterior diameter. There \\as clulJhing of the lingers and toes. On opening the thorax the lungs did not collapse but remained inflated, completely filling Loth pleural ca,itics. The majority of the pleural space was oblit~Tatl'd bilaterally by dense fibrous adhesions bet wei-n tlic \isccral a,\d parietal layers. Both the \isccral and parietal pleurae \,-er, markedly thickened, gray fibrous membranes 1111a,-uring up to 0.3 cm. thick. There were 100 cc. of clear straw-c-olorcd fluid locul:itccl in tlw left base. The intcrlob.ir fissures were oblitt-r.itcd by fibrous tissue. Scattered througl1out the adhcrc-nt layc1 ~ of the diaphragmatic pleura, especially on the right, were ;\ numLer of whitish gray, shin) plaques O.S cm. long; these- rcscmlilcd silllilar plaques II A~bcstosis, _Bronchogcnic Carcinoma-- 1ssdhacha cl al. t 1 I.,,.,.. ,. -~ .., {f>-~-- ......, , i I r I l l . i -. , . - ' 'ff' ..-'i' t, - ..- (. , 1 '/J--:~::_~~~:i\~r,}_/:_- -'.:-.-;~ ': -_: l ~ / J; ~ 4 ,: ~' :~ ~ ~ ' FIG. 3. .-\;bestosis ];,di,, in the lung. The club-shap,d, -,..~,.., : ,..7, _"..""7::--,C~\,J:'a. , a - ,., --~::..~:'..'j_~:_::~t:S~-:~~~;;~~~:~_:,_;~J FIG. 2. Cut su1 fa.:e of left lung aftc-1 fu: ::ialin fixation. uc:aded asbc,10,is lio:li,, ;uc sren in tlt,: ah,ol.1r due-ts, su1-,-ounckd by mac, opl,.,::;,s and 'dust c.-11,"; X 900. ,,as colla1y,c of the inttT\Tning parcnch: 111c1. :i'\otc di!Tu~c pul1nonary fibrosis and marktd pleural The \Tins and arteries appeared normal. thickening which obliterates th,:- intc-.-lobar fasure. There \HTe adhesions between the \'isceral and parietal p<'ricarclium both at the apex and seen on the upper surface of the lher, to be the base. The apical adhesions were thin fibrous described. The lungs weighed 2,710 gm., were strands but those at the base were extensions of ,oluminous and vc1y firm throughout; no dis- the firm tissue described in the left lower JoLe crete nodules could be felt. (fig. 2.) Multiple bronchus. The ht.:art ,,eighcJ 360 gm. There scctions showed a uniform hro,\'nish gray surf;1ce was imol\'emcnt of the kft atrium and auricle throughout except in the kf1 lower lobe where by thick, firn 1, grayish pink tissue for an area there a ppcar{'d to be a cliffuse m;1rkecl fibrosis measuring, 2.3 Ii) 0. 7 cm. The remaining 111) o- throughout the parcnchyma. The left lo\\"er cardium appe;_ired unimoh-cd and mcasured lube bronchu~ was compktely occluded 1 cm. 0.6 cm. thick in the riglit ,cntricle, 1.~ cm. in from its origin by pinkish gray, firm tis5uc fur a the left. The cnducarclium and , ah-rs \HTC <li~t;-.nce of 1.4 cm.; here the bronchus measured nt~gati, c. 0.7 cm. in diameter; the firm pinkish gray The diaphr,1;ms contai1wd firm grayish pink tissue extended into the pare:1chyma for a areas of plaque-like t!1ickc-ning which measured clistd11ce of 1.7 cm. SimiL.r ti~s11e extended from up to 0.5 cm. in diarnder. These \\ ere seen un this point i. the- bronchus to the pleura and into both the pleural and peritoneal surfaces, \\"Cre th, wall of ,he left atrium \\"hieh was adherent apposed and loose!) adherent to similar con- to the pleura at this point; the gross atrial in- fluent areas in Glisson's capsule. The remaining volvement mca~urcd 2.3 by 0.7 cm. in extent. organs, with tlw e:-.ccption of the fourth hunhar The upper lobe bronchi wen ri--_:.l and nar- \'C'rtebra, were negati\'c. This HTtcbra appl'an-d ro\\'cd by a thick, white fibrou, ,:. The right opaksccnt and rescmbkcl marlilc, but its con- lower an<l to some extent the I mi<ldlc and sistency was softer than the adjacent ,c-rte!Jrae. lc:ft lowr-r lobe bronchi ,, ere dii. d, and thc.rc The body appct1rcd to han: incrr-ascd powsity. A M I: k I CA 1' j OU k 1' A I. 0 F ~1 C n I CI :,; 1c: II! The scctioP nl',H tJera} an IJl seen Filno prulifcr the art am] pl p('rilJ1 c apices, demon fi I>rnsi.s t ft, ] d 11 a1 c;is l firtllCd .-11/,,-_ in all : fil >(TS SOllW C \\ liich prep.Jr prcpar larger, )',,"0\'I.\ J\sbcsto1;is, Bronchogcnic Carcinoma---Jssdhac/ier ti al. 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'l._"' ~ .. , ;: .f " ; t::!~~.J... -~-"--~,~":..':~-...,. ~,; t\" !' l , _ ,."=; ~~-;.-:-...,..,.,~, _..,.-. ..._... :_"""- ~.:-;;:~ ~-..-.~ ... :,t;-~-,:..:e~-_----.:--..:~:-7--~.r-..- .;...-:.,:....- t., ;--~ \ , , -..... ........ t-'..: .. ,'__..~ . ,f_,e.~t.,\ 1 .......~. --- .-., --~ ~--~t;...," o":~~:._. ~-- .;:-:, ......... \ -~-, &~~-~;.~~~ ='";;;.~!~:.i---~}~~;- ~ E!t:6';....__.;_.c..;..i'...-.-:-~..~--1,rt..-~-'-?!aC.-.r::.~--~<.:""....~~_.~t:.{~~-t:-:_..~;"t.-1~~=---."" ~.;.~!:::.~-hs:...;:.~;-., ;: ._t .~-... :,~;<-::..":v,....\...._"':!":"''- ,_~.__...: ''Di ~ ~:~~-1#"- ,- ~-i .:..,_'-.~- ""'\ -.....:::_~'-':-' -,..,~ ;_,.~"'r :_ \ <~...., -. .-r..- --~.. :-r: , (.. :!--.. ~i \ ' 1' \ll /, j.; .. .:;-:;.~<t~ ..-x_.... ,.,.;,4~ ..... :-"";"{;,,.;.~4".:.-".'..~_..- !,..~/,,~~ {;. ~ 4.;,. '; t:1 '"::\: -\.1:.~"-- ., . ..... ~--~:~tl:~".:-;:~_r,47~:,-;:~~.~ i;~_..::~.~,:::t:-:~~;;~,~~i-,,c 1:.:-1_::,:_{~';..,~.. .-;!1,!1-~f:' ..":f~,.,';;:~~~:c.~. ~ -t--.) ~ .t,.r-;:';.. \t. f ;, -:- -... ....:,, V t\ ,~.:-..-,f ;, . '- ~,; ..~.:.,a .;:;:, -..~-:-:.... \.t'l " ., ;~....,.,. -z,.11~,.;.. ~-,-..{.!"::,, >... "'.....<, f.. ':!\ .,. \ .... -;, ,.. -. ...... ,..:.ii' ~ 1 .. ...c.. ... ->.- t:,--.. ~- "' .. .-.-'". " "'"<I : ,, ~ ..,.../..-./.....,--..,..~,_;,i-,.-.~-',. 14~~-,>~~..._..,....;..i~. .l.,i.,,ttl'.."'.....j:-'-: . .,.:._. . ...',:.-<;-,,.r..~.,t-,,,,:......,,_.,_,,_,..,.,..,-,~':1.,~9'"~--f~r,,~-'"----'--~~:--'.~. ,.J... )i!~ ~-~-.l, ~7,,_,-._;~_.~Jo-:' t'/"'-.-..,\t:~~~~I I~---' \ :.,. -:/~-:_,, t j:f.,-...._ .... ~.!,,~ ...,""'- ...;."j ; ~;:.:J,"t~:-:--t'~f>'/{r-' r(; -~ ~..;:._,,,:-.....- "'; ~- ~~~~ ~/::; " ...,~ t l -' I ,f I C {' ,- ,\ ,- d I) ,~ \- d ll e - _! I' J - . . ,:;:,; 4 5 Fie. 4. Squamous mctaplasia in the aln:olar ducts; nc,te also a;licstn,is bodies ,,nd intn,titi,,I lil,ro,is; X 100. FIC. 5. Adcnocarci.noma invading the myocardium; )< 100. The lungs were t-cctionc-d topographically; sections from all segmental hronchi were taken near the hilum, the mid-lobar and the peripheral areas. These basic histologic patterns could be seen: Fibrosis: Throughout the lungs thc1e was proliferation of fibrous tissue around thl: bronchi, the- arteries, alveolar ducts; the intcrlobar septa and pleurae were also thickened. There was pcribronchial and alveolar duct fibrosis in both apiccs, and slight alveolar wall thickening as demonstrated by connecti,e tissue stains. The fibrosis incrcascd in the remaining portions of the lungs, was hcavic-st in the hilar and mid-lobar areas but extended to the pcripl1cry. This rnnfirmcd the gross impression of diffuse fibrosis. Asbestosis bodies: Asbestosis bodies we1e present in all sections. (Fig. 3.) These were segmented fibers averaging 50 long, some straight and som.". club-shaped, others rtscmblcd dumb bells which stained dark brown on hcmatoxylin-cosin preparations, and blue on Prussian blue (iron) preparations. Particles of iron-staining dust and larger, easily identifiable asbestosis body pa-rti- 11. ov E.M BE.R, 1953 des, were present in the 111acrophages. The distribution was equal bilaterally, being slight to moderate in the apic:il segments, quite marked in the remainder of the lung and occurring with equal intensity in the hilar, midlobar and peripheral zones. \\"hilc most of the asbestosis hodics were seen in the bronchioles and alveolar ducts, a few could be seen in the ah-coli, and fragmcnrs m;rc found lJoth in the macrophages and in the lymphatics. ScYcral aggregations of aslKstosis bodies were found in the bronchi. fragmcnt~-d a5bc~tos fibers were found mostly in the ma,ro. phagcs but occasional iron-staining particle~ ,nTe found free on the ,'.~--Tolar w::ills. :!\Juch, but by no means all, of this rnat<.:rial in the macrophagc-s took the iron stain. luflammatvry roj1onsc: The chief inf1anunatory cells responding to the irritant were the m;,crophagcs. These cells were seen in abundance in every section; they lined up along the wall.5 of the alwolar ducts, filkd the lurnina of bronchioles and ah-coli, and \\Crc found throughout the septa and fibrous tissue. :Most of these con- Asbcsto~is, Bronchogcnic Carcinoma -Jssr//iacher rt al. - :;~-:~;!~-/f-"~;.T-~~~.i.:~ .;~:~-~-~ .: _:~~~ ':. ~ - - -r~~ ~-~~_._:..~- \-:.~::r~~.:~:~ . rt0.:djjff:~:t~:h.c ~-, i:::~_::::.:~?SthS . FIG. 6. X-iay diffraction film of lung residue of E. ,R. The lines li~ll'd whc n compared to the l,,nown pattern for asbestos gi~c.11miti\"c p: ouf lhal the lung residue is c,,entially .t~bestos. \ < in,.i k occur " l'llllCL'11 n1bic fo t The f inh:ilat w he rather, Table of ''D"' lines: 4.52 2.42 1.61 i 4.20 2.38 1. 531 I \ 3.35 2.115 1. 49 2.98 1.84 1.44 2.67 1. 70 1.38 I * A 68.5 gm. sample of formalized lung tissue was digeslt:<l in 20 ,oluuws hydrogen pn o,.i<lc, the digc<tion being accekrated with gentle heatin~. The residue f, om the digcstiun w,H treated ,, ith d;Jutc hych ochloric ;ic.id, filtered, "ashed and ignited at 500F. The ignited residue was analy/.td U)' x-ray diffr.tlliun by the m,thod described in the article by Hanawalt, J. D., l~inn, H. \\'., F1c,cl, L. K., "Chemical analysis by >,.-1ay diff,ction," ]11d11st. & F:11,!!, Clw11., AMI. Ed., vol. 10, no. 9, 193S. This w01k was done by R. I. ChAmbcrlin and:\. \\'ocwucl-.i, Jr. oftl,c :'\fa.s,.trliusctts Bonding and Insurann: Company, Boston, :\fass. rrorn fi The in to pil5-S so they rc.icti,> The:- p con,ick dc,q11:11 ,>f a,-\,e Tlic li,ling tainccl brown pigment granules rn:rnr of \\hich B!oud Vl's.1r/J: Thc arteries ;mcl arterioles of the i1 I ita ti took an iron stain, and portions of asbc~tosis right middle and buth lower lolics sho,,-cd 111at1.:. bodies ,n-rc also found in the m;,crophagcs. (Thcsr cells have been called clust cells :.ind arc moderate intirnal thickening with hyalinization ancl naiTo\\cd lurnina. This \\as most nwrkecl phagol ;tslw~t, thought to lay do\\'n the iron on the asbestos fiber, constituting the asbestosis lmcly.) Anthracotic pigmc-nt was also present in the macrophages. M ultinuckatn:l giant cells of the foreign near the hila but ,,as found occa~ionall) farther into the periphery. Tunu,r: Adenocarcinoma ,, as found 01 iginating in the infn io1 lingual scgn1cnt of the kft pli;igv: .1,lwst, ,o-c,ill f10111 , Locly type were found in abunda11cc in all areas; upper lobe lJronchus. The tu111or was present partic many of these contained birefringent asteroidal in the mid-zonal area of the :qiical pmtcriur ing o! lioclies. Few 1) rnphocytcs ._n:rc seen; those present were scattered around the bronchi near the hila. A few focal areas of bronchopnn1- segment of th<.: kft upplT lobe, the entire lingula and kft lo,\'Cr lobe, as well as the right middle and lower lobes. It had spread by suh- cour.,< ,, h icl irrit.i monia with polymorphonuckar infiltration were present; these had no particular rclatiun or location to any grouping of the asbestosis Ladies mucosal and lymphatic routts. Sections of the left atrium showed clirl.'rt extension through the left hilum into the pericardium and myoc;;r- ,p11tu Thi1 to asl and were unclouhtcdly a terrnin.il phenomenon. Throughout the lungs many air sacs were dilated a11d contained a granular eosinophilic material, probably fibrin. Some of these plugs \,ere undergoing org,mization, mainly in al\"e- clium. (Fi~. 5.) Metastatic tumor was seen in the fourth lumbar ,-cndira. Ashrstos "g1m111lo111as": The \\'hite plaques dcserilwd in the diaphragm and Glisson's capsule \\'ere made up chiefly of h) alinizcd con- ::n ir Tl is th tion :md olar ducts; this type vf fibru~is probably accounts nc:;c-ti,e tissue. 1\'o asbestosis IJodies or giant corn for :-i srn,dl percentage of the total fibrosis seen. cells \\Crc scen. Thcse clistincti\'e areas grossly in Cl H1011rl1i: The l,ronchi of the lower lobes sho\\cd sug~csll.'d gr;rnulomas. 11,H) markc<l Lronchiectasis; there was dilatation, X-ray diffraction studies ,,ere ca1 ricd out on the fibrosis of the muscular coat and pcribronchial a sampk of fornializcd lung tissue. The resulting par: fibrosis. \\1hile the latter \\'as most marked in pattern indicated that the lung residue was a fi the lower lobes it wa,; seen in the hilar and mid- mostly asbestos. (Fig. 6.) lo" zonal regions of ali, -i~t all segments. Another up1 striking feature w,b wicksprcad squamous CO~!~m:-:Ts metaplasia of the bronchial epithelium. (Fig. 4.) Asbestosis may lie <lcfint'd as a ~pccific occu- pre This was most marked in the alveolar ducts; it pational disease caused by tlw inhalation of tell was found in all areas and was not particular})' a~bestos fibers and leading tu a progrcssi,c Cl.'c related topographically to the adcnocarcinoma fibrosis and scarring ,rithin the lungs. 17 It ha,; to de!.rribed later. been ck111onstratcd by Gard1wr~0 and ;igain by tio Asbestosis, Bronchogcnic Carcinoma- -Jssrlbad1cr rt al. \ ornald 1~ that usually the disease will not .In grncral there is a clday of fiw to scHn .,crnr with fibcri: ki-:s than 20 in length or a years bct\\ecn the initial exposure to high con- r"11ccntration below fi\"e million particles per. centrations of asbestos dusts and the onset of o1hic foot of air. clinical asbestosis. The a,cragC' interval re- Tin~ pathologic processes re~ulting from the ported by -r--Icr<.'\\-cthcr is elcn-n years. 17 \ \'hilc inhalaticm of .-asbestos particles arc hclicYc-d most patients ,dth asbcstusis han_ had an to lie due: not to their che111in1l nature but, c:-.posure of ten to si.<te('n years, it is important :,itlwr, thr conscqup1cc- of mechanical irritation to r<";ilizc that the disease has occurred with as fi 1>111 fibers lodged in the respirator}' trce. 1s-:o short an industrial exposure as 0.5 years. 12 The inhakd particles arl', in general, too large Usually no S) mptoms appear until a large 10 pass beyond the respiratory bronchioles and part of the rc3pir2.tory rcsc1TC has been reduced _,o they remain there to initiate a fordgn body by the fibrosis. ~krcwcthcr has frcgucntly com- reaction ,\hich n-cnt ually leads to fibrosis. 21 mented ho,, markedly th<' lungs can be affected Tlw pathologic sequence of cnnts can he and )Ct the patient be fairly comfurtahlc. 17 cunsiclercd as occurring in three stages: (1) HoweYer, when symptoms once bcgin and d,,quamation and n,mlation, (2) formation significant dyspnea lxcorncs apparent, then is "f ;:sliestosis bodies and (3) filJrosis and scarring. usually a definitc and rapid progn.l-sion. Then The long fibl"rs traumatize thC" epithdial cells producti,-c cough, anorexia, ,\Tight lose; and lining the smaller bronchioles and the constant fatigue arc thc common complaints. Death irritation and friction cause the fflls to dcsqua- eventually result~ from intncurrcnt ink( tion, m:l!c. t>-1acrophages pour fortli in an effort to eor pulmonak- or carcinoma of the lung. ph;igocytizc the fibers. In our case fragm<'nkd The Ca!>c ht-rein presented tkrnonstratcs many ;1~l>cstosis ho<lie~ were ;ibo se<'n "ithin macTo- of the significant ft-aturcs in the p:itlwgnwsis, ph,1gcs :me! lymphatics. A second rcac-tion to thc s;-mpiornatolog: ;incl n,tlurnl course 0Ca,l1l,,1osis. :1sbc,tlJ, fiber in thc lung is tlic production of thc- The pa1i,nt Lad worked for t\lcln years in an s(1-calkd "asbestosis liody." 21-~ 4 This results atmosphere ha\ing a concentration of a~lwsto< lrom a reaction occurring het\\'een the asbestos particles known to be suffiriC'nt to p1 odtHT p:irticlc and surrounding tis~ucs. It is a thicken- pulmonary p;ithology. Hm, c,cr, it ,,a~ on!) ing of the fiber due to the dcposition along its during the last year of life th;it d~ spnea, cough, c,n1rsc of a protein matrix containing iron anorexia and \\'tight loss rnanifcst(d tlwmsdn:-s. ,,hich probably serves to n-ducc thC" chronic Clubbing h,id !wen prcscnt for at lc;ist five irritation.~" Tlwse bodies may l1e found in the years. He had a wry rapid downhill cow sc, dm sputum, lung, pleura, lymph nodes and spleen.~$ undoubtedly to the two <1ssociatcd factors--thc Tlwir presence is held to be c\'idtncc of exposure asbestosis and carcinoma of the lung. The to asbestos but hy themselves are not necessarily physical findings of cluhliing, cyanosis and ,111 indication of ashcstosis. 1i, 27 ,26 dullness at the lung bases were all consistent The third and most significant tissue r, sponse with .isbestosi~ as \\'ere the x-ray findings in the i::. the production of filJroblasts and the deposi- Ju :~, .:part from the c\'i<lcncc ,uggcsting nco- tion of coll;1gcn about 1hc distal hronchiolt"s pb~m. Thc out!'tanding s: .11ptom, the severe and aheoli. There ensues a cliffusl.' fibrosis which and prog-rc~sivc dyspnea, was ;ittrilrntcd to a cornprcsst"S thC' ahToli and capilJ;wics, resulting combination of pulmon;iry fibrosis, superim- i11 complete obliteration of the invol\'cd pulmo- posed and spreading lung neoph1srn, pulmon;iry nary tissue. This process is more pronouncC'd in infection and fin::illy congcstin failuic on the the lo\,cr lobes of the lung for it is there that the basis of cor pulrnon;ilc. particks are mo~t abundant. Br x-ray one scrs As indicated in the case histor:, the trn-d.-1y a fine, ground glass or granular pattern in the period of .'\CTH therapy was accomp;rnird or.I} lower lobes and frequently emphysema in the by euphoria but objcctin me;isurcnwnts rc- upper lobes. vca1'-d no significant changes. This was not The sc-quencc of pathologic C\"Cnts c.kscrilxd suq,rising for two rea~ons: (1) the fibrosis had previously occurs slowly. In man the fibrosis ob,iously been of long duration and therefore tends to progress even after the c:vposurc has one would not expect it to cha11gc nrnch at this ceased; ho\,-c,c1 in animals this docs not seem time; and (2) he had rnpcrirnposcd 1Jroncho- to be the case. lt m;iy he that intcrcurr<"nt infec- 3c-nic carcinoma. It is of interest to comp.ire ~ . tion contrilmtes to the progression in man. 11 these- rc~ults to patiznts with chronic IJerylli111n ~ i,; 0 \' E M J\ 1: R ' l 9 5 3 L A~bcstosis, Bronchogcnic Carcinoma----lssr/1,arhrr fl al. poisoning who usually show a fa,urahlr re, sponsc to ~tcroicl therapy. 2 _ Two further aspects of this case merit more dctaikd consideration and analysis: (1) the pulmonary function and cardiac cathctcrization studies; and (2) the sigr,ificance of the superi,11posed broncl1ogcnic carcinom~.. num!Jcr to be of significance; otl,ers, especially Von\"alcl and Karr, haYc stated that "inhak<l dusts, txccpt those cnntaining recog11izecl carcinogenic substances (as radium and tar) cannot in gcn<:ral be cor,,iJcred as etiologic factors in the development of prim;iry pulmonary carci- T.... H1.r: Ill the pne series S. cuniusis 1 Gloync't pC1iod ,. to intLT\ 1 the inn 1 PUD!O=-:.~RY FC:--.1..TJu:,; ..\.."-:0 C..\RDJAC ISClDEscr. OF ..S..5.HF.S."l(J<:::ts ASD C.\RCl:\"0~1.ti. Of LU~C populat' C:.\TiiJ.:TEIHZ \"fJ(J:,; 5Tt:l>JE.S I Table 1 indicates, as one might e~pcct, that I the patient had a rtduction in ,ital and maxi- .\Hhor Xo. of j D,aths "ith .\,b<"sto;is ~u. Due to Carnc1 of l,ung Incidence (7c) mum breathing capacities. Howc,-cr, the finding of an ah-colar-artcrial oxysrn gradient of I 27 mm. Hg dnnonstrates that on,.- of the dis- l\krcwcther' ..... II 235 turbances in pulmonary function ,,;!s a defect WWcydelrcsr' .'.................. :: 11925 31 13 2 15 16.3 17 14 8 }l in the diffusion of oxyg('n from the :ih-eoli of the Lynch, Cannon'; .. i 40 3 7.S lungs to the capillaries. Tr.is corrcspo1,ds to the Glo}ne3 ; 121 17 14 1 syndrome of "ah-cob.r-capil!.lry block" de- -----,----- ----- I scribctl by Baldwin, Cournand and Richards 3 1.32 Total. ........... l 603 83 13 8 and ag;iin by Austrian er aJ.?-i This diffusion I defect is not surp: isin; v. hen one recalls the noina:~ Our conclusion at present is in fayor l fibrosis about the aln:oH, 2ln:olar ducts, capil- of the concept that the association of broncho- laries ,md bronchioles that occurs in aslicstosis. genic carcinoma ,,ith asbestosis is more than In order for the patient to maintain a near coincidence. That there is a significant incidrnce normal artnial ox)gcn saturation, a high of lJronchogenic carcinoma in ;isbcstosis is ahcoLir oxygen ,,:is n('Cts3ary; and this ap- app;irent from Tal>le III. parently was accomplisl-.ccl in part by hyper- Mcrewethcr has cited the largest series -of ventilati.,n. The p:,!ient had ?.n a,cTa~e 235 ca,es of asbl'stosis there \\"C'IT thirty-one with .J re~piratory rate of 40 per rni:mte at n:st. This bronchogC'nic c;,rcinoma, or 13.2 per ccnt. 1 An cvrnpcm ,tory mcch;rni,m :1p1):-trcntly was not an:ragc of the fi\e analyses rccc,rded in the adeq:1atc clui-ing stres!- or excrcis(' for uncler literature is 13.8 per cent. This is comidcralJ!y those conclitiuns the ancri:i.l oxygen saturation higher than the incidence of lung carcinoma fell. There was a consid:r::i!Jle degree uf pulmo- in routine necrop,ies, which in a comparable nary hypertension and, as in the t';iscs of pulmo~ nary fibrosis studied by Cournand and his period (1935-1948) ranged from 0.8 to 2.4 per cent. 9,4 ,_;4 associates, a rise in the pulmonary artery In contrast to asbestosis the inciclcnct of pressure- occurred with <::-..erci:'e. (Table n.) The bronchogcnic carcino111a in silicosis as recorded partial pressure of carbon dioxide in the blood in the two l.::.rgest snics has lxrn similar to (36 111111. Hg) was lo" no:-mal rather than ele- what might be e:-..pccted in the general popula- \'atcd. Had there been a defect in alnolar tion. The data co1i1pilnl by J\.fcremtlicr1 rind n:ntilati<,n, the pCO~ ,,mild probably have the ~Iiners Phthisis ~kdical Bureau of South been higher. As Arnot c:11p:1a~izcd in disrns~ing Africa 50 are based on a total of 6,884 and 1,438 this casc-16 larlion rlio:-,;idc is not impilircd in autopsicd cases of silicosis n,pcctiycJy, and its trdmJc:r from the- bluud to the aheoli because disclose an incicknce of lung carcinoma of o::-o of its great difTu~ion capacity. This !-p,xd of 1.32 and per cent. \orwald and Karr found diffusion plus the increased ah-colar wntilation two lung carcinomas in 136 silicotics (1.4 7 per no doubt accounted for the lowered pCO2 \'alue. cent). Klotz 06 noted an incidence of 8 per cent, ASflEST()SJS AND C.\RCJ:--:0'-1..\ OF 1 HE LUNG but his series of fifty cases docs not seem large enough to be ~tatistically significant. However The association of asbcstosi; ancl carcinoma Gloync~ in. re,icwing necropsy material from of the lung has been m-::mio:-1('cl frequently in 1929 to 1949 (796 cases) also dcscribc-d the the liter:1 turc. 1- 3,34-3 Hcreroforc some authors surprisingly high incidence of hmg carcinoma ha,e bdit'nd that the cases were too few in in silicosis of 6.9 per cent, and 7.7 per cent in l,Jy is l 111a tc-ria in "\iicl! Glov1 "ith a'sll p;ir;dkl. ;rncl is 1 silico,is.1 panick, ,,Lile t con~ick siliczi. 1' Care ncnt in tliit l'.'-C. cent, zi' 1hr inci ;1 u 1np~\, arc- a\ (21 pc inciclc:1 in the- 1 Lincl;:\., Crahi!c rent ;11 figure ash<:!-to E:--p< clcrno11 ti~,ues tl1e ck ticks, a~ me, 1]1 c} i\I I fcmnd con,cc l ,'spir; !--CJUan cdluh initial cell c A' possil i~ cha that e.,pm A~IERICA!-. JOUR1'AL OF UI.:DICINE ,uvE .. ~ .... _:..:...~:-............:,;.:~...;...~::;.'.~~-,;..~.--~ :---~:~.;,":;., ,_-. - : ~..- . ~ ~ . . . : :..........:.:.:....:;.__.__;.,.;_ ----------- - Ill rci- - I 2 .3 F, s .R l\'C.,J' ,Lo!i;,n ,nrc s 1, .-..f.l,.[ \\'it!i I An I Jhc- ably 1oma t ,able f 1 per I :c of 1r(kd nr to pula- and Otith 1,438 and i of ound per ent, L1rgc ('\'Cr rom the I oma '.:, ,~~ 1 I Asbestosis, Bronchogcnic Carcinoma-Jsselbar.ha rt al. the pnn1moconioscs as a whole. In this same ~cries 8.3 per cent of cases without any pneumoconiosis had cancer of the lung. Mcrcwcthcr and Gloyne's casrs were analyzed oYrr a comparable period of time so that it scrms unreawnahlc w intcrj,rct the figure of 6.9 per cent as rcflcctin!; 1hr incrc':s~ of lung carcinoma in the general population.'-The discrepancy in the data probably is explained by the fact that Gloyne's material was sell'ctcd from the pneumoconioses in which the historks and x-rays were "unusual." Gloyne noted that 14.1 per cent of patients \\ ith aslxstosis had hmg carcinoma. This figure p:walkls the observations of JXeYious workers and is significantly above that recorded for silicosis. As has bern mentioned the asbestos p:irtick probably acts as a mechanical irritant ,, hilc the pulinonary changes in silicosis arc ronsidrrC'd due to the chemical properties of ~i!ica.1s.20 Carcinoma of the lung appears to be prominent in females "ith asbestosis. Of ?vfc-rcwcther's thirty-one cases nine were fcmaks, or 29 per cent, and in Gloync-'s srries of scvc-ntccn cases the- incidence was 41 per cent. In the published autopsy reports data as to the sex of the patient arc available in t\\'enty-threc, of wh ;ch five (21 per rent) were frmalcs. In contrast, the incidence of bronchogcnic carcinorn~t in frmalcs in the general population is considcrnbly IO\HT. Lindskog noted an incidence of 4.0 per cent,b7 Graham 7 5.4 per cent, Doll and Hill 6 8.4 per cent and Ochsner10 10.3 per cent. The highc1 figure in aslx~!o!-is supports the theory that asbc-stos particles act as carcinogens. Experimental production of neoplasms has demonstrated that chronic irritation of body ti!-sues by mrchanical means may predispose to the dC\cloprnent of malignnney. Asbestos particles when lodg,d in the finer bronchioles scnc as mcchanicnl irritants to the bronchial epithdium. The squamous mctaplasia of the lungs found frcqurntly in asbestosis is presumably a consequence of prolonged irritation in the lower respiratory tract. Some pathologi~ts consider squamous mctaplasia as an alteration in the cellular structure that may precede or be the initial step towards the development of squamous cell carcinoma. I>6 A "lag period" bct,H'cn the exposure to a possible carcinogen and the onset of malignancy is characteristic. Nordmannu noted in his cases that the average duration between the initial exposure to aslwstos and the development of bronchogrnic carcinoma was about eig-htccn years. Similarly Mcrcwcthcr 1 found that patirnts dying of carcinoma of the lung had a longer mean exposure to asbestos (16.S years) than those dying with no evidence of malignancy {13.4 years). Finally, a short but "adequate" exposure may be followed by pulmonary malignancy many years later. In 1\'fcrrwethcrs series is the case of a \\oman who was an asbc-stos ,rnrker for only six months yet later ckwlopcd lung carcinoma. Gloyne~5 reported the case of a wort'1an \\'ith an exposure of nineteen months \\ho died fifteen years later at the age ofsc\'C'ntronc with a squamous cell carcinoma of the right lower lobe. Table n- summariLcs the pertinent information of the twenty cases of asbestosis with hmg carcinoma th:-it haw: bccn autopsied and recorded in the available literature. Four C'il$C'S haYe been added to the list compiled by Homburg, rH in 1943. It is noted that in about fourfifrhs of the cases in \\'hich the primary site is indicated thr origin of the neoplasms was in the Jo,\cr lob,s. This is in contr~1st to the general population where bronchogc-nic carcinomil seems lO Le more frrriucnt in the upper lobes. In Lindskog'sh9 series there was an incidence of 57 pc-r cent in the upper lobes, 26 per rent in the lo\,er lobes. Od1sncr 10 found SG per unt in the upper lobrs and 35 per rent in the lowc-r lobes. No condl!Sions should be drawn from the small number of cases listed in Tal>lc 1v. ::'\e\'erthcless, since asbestos particks lodge to a greater extent in the lower respiratory trc-c where the changes of asbestosis an also more pronounced,. a higher incidence- of carcinoma in this location should be expcctc-d if an etiologic rclatiomhip exists. In our case the asbc~tosis was widespread and severe, and the tumor, which originated in the inferior (lin~ual) sc-gmcnt of the left 11ppcr lobe, \\as 111 an nrca signific:mtly imoh-cd by the fibrosis ;rnd inflmnmation of asbestosis. It is ,1hl) notf'd in Table 1v that 11,-che of the ninctren prc\'iuusly recorckd c,ises had lc~iom of the sriuamous cdl type. The incidence of squamous cell carcinoma is said to be high in male cig,uctte smokers with pulmonary malignancy. 6 At autopsy our patient showed both squamo11s mctaplasia and adcnocarcinoma of the lingula. It may be of significance that he "as a chain ~molcr for o,er twenty years in \icw of the ob1;<'1Tation by \\'yn<lcr :rnd Graham 7 th;,it males with adcnocarcinoma of the lung arc I\OVl;Ml<F.R, 1953 - II_-,'- ,~- ,,,,,-~- - --- ,'-~............ ~>.I--,,---,..__.__..;.. - ~ ,_J,..... ,~........... . v ,\:-dx~to.-;is, Brunchugcnic Carcir101na frniucntly chain ~ll11Jl;crs. Hm,c,Tr, it is our lJdid 1h;1t the prncnct of an adenocncinoma r;ithn 1h;m om: of the ,quarnous cdl type may. h, c.,plaincd by the foct that it is not unusual ru find snerill cclluhr i) pes in \'arious S('Ctions of 1he same tumor. 5 ' Therefore morphologic c,ircinoma in 13.S per cent of tlic ca,cs t ikcl in the litcraiun. In silicosis the incid\'l1l'l' is cr,nsidnably less than this. Tlic: :dJl'stu, p:1rlick ma: ~l'f\T as a c;1rcinugcn IJl'c:iusc of the rhrunic 1mch:rnical irrit:1tiu11 it prmlun,._ 5. Since tltne dl"C appru,irn:nl'ly 10,rIuo TABLE I\' Sl,1\1\L\RY or ll"J,l.l<;,IJ-:lJ C.-\SE ]{E}'(liZTS IX \\'JllU! ,\l TCJl'SY D.\T.-\ .\R.C: (;J'JED ------- . .\utlior)< Clo~ !)t 1 ~ .. (;J(Jy11<. L:~!u:rt. Cti_',CJ.:JI. C!uyHc:t .. ~ ,-,.' .,, 1 ,. -,I!I 11)3) ,II 1c:is i I 1J3~ I I I 1936 .. i 1936 193~ ~ex :ind .\ee ()1 niJi:l!i(1n l---~)111:t!;,,n of }~,pi1q11c ()L) I \f . .'.\7 \\"t:!\rr F, 3S Spinner r. 71 I \_Ltfll('',; ;111d open- ' 111g d,p:!!lJ:h'tl(!-. \1,..: 1 \\'<-:J\ er \!., :i'J Pc1d.n. ~: 1H<> c.l(""- ( varnnnll F. 3S: Ca1dn. ,p;nucr, 11 I 7 10_1:, :'( >J drn. t,n \ 'Jlli \I._;, !'",pinning ,-1..,,,-,nh)~- rtJ1n1 l 1!1'J \I,_)() \\"\.-1\C'I 13 l :1:1L.1,!.. \\'cJ!n 41. I ) ~; I !C' 1 I( ' C \ .) l. ~..I . !) .,,.)l:ll :c. t'! .d. }l 1uhu1 ('":l c~ ) J. mhll:~,~r. }lnml,u::.t1 .. . i I '14 l I l 'J4 \ 1<1..;1 \!. &1 :,.t_ - \1. \L 4~ .\f. ---,_.l J, ~') ;\Li, l:ii: .1c:_1;1,1ur J=i,t~'.\._',U ~-n,_ k11(1\\n ~-{,, \ lHJhn ~l>; ,;J',\fl I lHl\;1ct ,, i[f ,,i.~linto.~ 2S > 3 25 ?.2 20 (),\ii,i-1_ ~;l'iJ. II ..~s, :\ngrl~ti:-: __ l 'JS l 1'JS I \1. :/1 .-\~!Jt-;10, v,ud.cr _\1, sl(I' l'ifl' ('O\l.]("J \f -: 1 .\(L,v:o~ 111d! 1 \\(J;{c1: "-Oilt"r frp.~'JIO f111:;J [:-,.;-_.,,,.urc 1....-f,)lt' f)~."l:h ""'"'I i i I'" r 1. I 1"""' u Prioi.11}" Slit I) yr. 15 yr. i s<1:J.,1no:1~, r-11 I 1 Sq11.1!1)(.Hl' (df '~qi. t!TIU'IS ( tll I ' J..t LL. k.l:.L. IU .. L. I I ' 1.1 1~ f' J,: J, L. l'kllr .1 !\ l II], ..., '\u11(" ) yr. 1() ~ r. 1 !ll() -1 rnr;. 1 " l..., n,u ~r, YI. :\IJu1.:t -1- ll c:Lu1d11l.1r 0.1t tell I.I.I.. 1.1..l. I l..l .I.. ; S,11,,1ml!:J"- \\i:fl 1 i,;Lndu!.tr I fr.1[urc.,. :\", >" ~- , r ., : i :1 i;, ! lni :JJH)US " , : O.n <-::-l! ! s~ 11,.1:1H1ti, ( ell \hc,.\..r rrl! ; S,.p1.1:1nu,: ell ; Sqt1.:11110: cell \ri.1ph-:t1( , ~q'.:,11n(11,, <ell h:.L.L. i R l. l. : JU_f._ ; I, li:ll'...'. 'R !uw: ::( i'.lt~ : },:, lunt..; l..l..l.. ' :\dc:wc.ti cirHJJll.t ! 5 ~ r . .\n.:tp!..stic II . .-\dniucJJ cirullna lZ. Iunb ~o ddinl\c' sitt' I .i11~ t1l.i iI \\"I( l,-~p1 <'. .i.i I. l' .1 ; nl p!111r,1. : Li\ er, i.i, 1ic> ... I . \\;.1, 'I'"' .,d I P:n1r.1. 11-nJi- i ,1-.:111,d I odes :\"one , l'k11r,1 : l'ict!? ,l l>).q,l.1. . 1'l('\IJ0:1 J .i\ 1:1, .-td c:1.d, SlO:ll.H )_, hll;1 I I~ m1,L 1 -1d{'.'- !i l'ci i, ,n ~! dll, I J..j, :/1('\", ()\ .ll ;l'~i I r.-n1t1~ ; ~un1: ! L.idn ]i\ Cl n- . . . li::1in, \f: ,i. .1rd :11:1, 1,cri- c;111 :it111 , ~[>Ii::.':, f( b:t1:~.,l 11udt~ 1 diffc,,nns rn cell arr;rn~cnH111s may not rc,ill) r,;;rc:;cnt diffrrcn1 ctiolu,:-ic , arictics of cancer. 1. :\ case- uf aslicsto,is \,ith supcTiill/HJscd ;,ckn,,c,rcinuin:i of 1hc lu11~ \\ ith nwL1.,t;1scs, fullcn,iilg docurn,ntcd k,rnJul indu',trial cxposur(', is prescnl<'cl. 2_ ACTH (;1drc-noconicotrophic l:orrno1w) was !!l\Tll ,,ith no olijec1in' chan6cs in the patient's clinical cour~t. 3. Puln1cm:1ry fullctiim ;,nd cardi:1c c1tlll'tcriz:t1iun ~tudies were pnfurrnld bcfofl' :ind ,iftcr .'\CTd. They 1T'.cakd an ,1heolar diffusion defl'ct ;ind pulmonary hypi.:nn1sion. 4. A~bc,tos i~ ,1~soci<1tccl "ith lJro11chog1nic \HJrkcT, c11gag(-d m potcnti:11!y ku;ird,.,u, aslJc",lU\ upnations in tliis cu11nt1y, it is c:1:m;il>lc tu ;1,,u1nt i\1:11 there arc n1:JI1)' 1,n1,-ct'g11i;-.cci c;1sis of ;:,Ll'stusis. f'ru1n the nick1;u pn ,-.;1tcd ,i high,-r incicknn of ll!'uncl:<J'.',l'ilic t :11 < 11:u11u shuulcl l,c c:\p,_ctnl in this ,:ruup. .lr/r/,-,,,,';;n;: Si!lCl' tl!, ,ulrn1is,iun of ti:;, 111c11uscript a siu1ilar case has li1-c11 olJstrY.'cl IJy us (l\lCH ;77820'i). The p:1ticnt \\:ts a furt,-si:--; year old Cci11tr:1ctors helper ,, hose \,or:-: ,illCC age sc\n1tcen cun:~ist("(I uf cutting and ,;iwing aslJc,:rus l;c,ard to in,uh 1l' pi pcs, boi k s :rncl n'frigcrmors. For ) till's he had s1nokcd one pacbgc of ci~anttcs cbily. I k died afin a ycM of illness dt1ri11~ the bot fuur rnnnths uf \'>hich he ffCTi, 1d ,~,1)(10 r of dffp ;,.,:-ray (u the ld. chest. 0 Jlli i'\( l_j !, II'. 1 I I' / Idin l lJt1- (iCk t!1e I,f /I){) n.t!, hd. 1 1 JC:\ll1, Ill!\. jlt . "'!';:}, :,.- .. \1, i...: ~ l ~I..) i1 - ~ 1) lzcc~ .'\I_ n 1,_c: ill;JJJU- hy 11,rt y-si, ,i11c,: ;1\\ln~ s a nci d one a , car . ,,, l1irh , 1 '"l. .'\ 1 /,.,.,_.,;,_,,,_,_,_,.,_ e,.,...,~.....,_._:~_"._...., ...... :~- ~........................: .:.,,,.___._._ __,_..,. ~~..:.-:.~.........~-;,.....,__....:._- ..~-~~ _;:__-..,._,,.,,. ' . Asbcqosis, Bronchogcnic Carcinrnm, !.1sdbocl1rr l'i al. .\t :1utopsy the lungs ,,T1-c finn and \\'cighccl :,,.;.:;o gm. There w,1s a poorly diffcrcntizitcd :1dcnocarci11oma ,ni~ins from the left lower lobe l,ronchus, ;ilmost co111pktdy rcpl,icing 'the kft lu11cr lube. The l urnor had spread to the left 11ppn- .)olJC, hilurn, pnicardium, pleura and di:1phragrn; ilncl had mct;1stasizcd to the right lung anc'l ~adrenal. The rLrnaining hrng tissue :chu,,Td pnilironchial filirnsis, foc.d aln:olar wall thickening and 11u1nc-rc>'1, asbestosis 1Jodi,:s, surru11mkd by rn::icruph:1gcs filkd ,,ith asbestosis I,udy p,wticks ;111d fon-ign body gi,,nt cdls. The 11slic,lo,is lJ()di,:~ \,Tn s,Yn in equal clistriliutio;\ in :tl! p;1rts of the lu1igs not CullljJktdy imolvl'd IJy t11J11or. 1. \lr.;,r:,,r1 liLR, E. R. ,\ ...\)lrrnal Rq,on of the Chief l!!<pcctor of F<1ctu1,,s. J.,mdon, 1947. H. \1. St;nirmci y Office. 2. \\~1t.rz\:, lL .\~bcstl>sis. Pu1f. G~ra,!. _,\J. J., 25: 631, 1 ')4~. 3. (~x_oy_,,,,;E, S. R. Pncu1nl)cuniosis. ;\ histulo~ic sur,d_-y of Jl!"fTOi)s:.y lli<1tc1i;d in 12n:) Cl_-.,l'S. f.til!Ct'(, 1: 810, 19'iL 4. \t<JK\\ ..-...1.v 1 .'\. J. <1nd }~ \J~}.:._, J. \\' Pneurnoc1inio...:i'' and pul;11orj~try c;trci11urna. .:1m. J. Potlt. 1 14: 40. 19:18. :-i. VO}{\,.ALD. :\. J. Pcr:-.on:J n.i:~:-::u1!;c:1ticn 1 1952. 6. (;lL\Il.s\\1, E. :\. Prirn::ry c1nctT uf the h1ng ,,ith sp,,cial considc.ration of its c1iology. /lull. Xn, fork c1{(Jd. ,\!of., 27: 261, J9S1. , . \\'y:,r,cR, E. L. and G1, ..,1,,'.,1, E. A. Tul,:,cco ,.mok- ing as ct pu-.sibk etiologic f:1ctor in bro11cl1ogi-nic Glffinoma . .I. A. :If. A., 143: 320, 1950. 8. Dou.. R. and HH.L, ,\. 13. S,nukin:; and c:,rcinc.ma of dw lung. Preliminary Report. 8ril. :\f. .!., 2: 739, J9:iO. 9. Ot:ll'i'CER, .\ . .llld D,:H.,KEY, \1. E. C:ucin01na of the Jun;.:. :1,rh. S:11g., 42: 209, 1941. 10. Oc11,:--;,:1c, .\., ])d1,,1-:1:y, 2\1. L, DEC-,,.11, l'. T. and HAY 1 (~ .l. Bru11cllc1~<.nic- ca1 cino1na . .l. A. _,\f. A., 148: 69!, 19:,2, 1 L L;c,;1.A, A. J. Pnsoual cornrnu11ication, 1952. 12. L,';; A. :\ . .I. Silicosis and Aslwstu,is, p. 386. N,w York, 19:08. (hf,nd lilliv. Pnss. B. !ckrn, p. 327. 14. \\'oo:>, \\'. B. and Gu1v,-;1-:, S. R. J\,l111cm;in ;i:bcstosis. l.u11ctl, 1: 445, 1930. 1 S. \h:1n-:\':LTHt:R, E. R. /\. and P1ur.r., C. \\'. ]{cport on the Fffrcts of ..\slxst"s Dils! nn the Lungs :ind Dust Suppfcssion in the As!J('Slos Industry. London, 1930. B. o'<L S1.1tiunery Office. 16. Ca.SL Records of the ~i :,ssachusdts Gcn~ral l luspita! (csc- 3S221). :Ym f:;11g!1111d J. ;\/,-d, 246: 867, 1952. 17. 1'fr.><E\,1:r11c><, E. R. A. ;\ memorandum on a:sbes- HJsis. T11l,nrlt, 15: G9, 109, 1933; T11iodr, 15: 152, 193 1~. 18. \'cmWALD, :\. J., Di:Ri-,,N, T ..M. and Pr,xrr, n. C. / Expcrinwntal studiLs on adwstosis. Arch. Indus/. s_ 11J.!f, 3: 1, 1951. 19. (;LOYSE, R.. R.caction of tiss.lll'S 1o ~1!-hCShJS fibre-) ,,!th reference tu p11l111un:-1xy ;t~hcst 1--.:.i,:;. 'Fn!1_,,c/t 1 11: 1.;1, 1930. 20. GAKD:--.Tl-<~ L. L:. l',tiuk1?;y of pn:t11lltJ(oniu~ii;. J. :I. .\!. A., 1 l 1: 1925, 1'.7:l8. 21. G/daJr,;Fk, L. l'. and Cc,1,11,;c;s, D. 1:,. S1udi,c, on t::\pc-ri1nnnal 1n1tun1ucu11iosi.s: VI. Jnh~tl:ttion of aslit_"5to..; <ll:-:.t; ib tfftct u.pon print.i y tulJcrclll>H1~ infection. J. l,:,l,,,t. IIJ.~., 1:,: 65, 97, 19,1. 12. Cr,oi;,;, \\'. E ..\,l,v,to.s dust ;rnd tlw cll1io11s ho,Ecs found in pulmc,n:u-y ;;;l,c,tosis. !lril . .\! . .!., 2: -~;'8, 1'!29. 23. \le Dos \LI), S. Hi~tolu~y of pul11w1 .iry :ishst,,,i,. Brit. .\I. .I., 2: 102'>, 1927. 24. Siu,.,nT, \I. J. :rnd lL,1,11(1\\', /\. C. D,1"<n1;t,.,tion of the ptc11Ji,1r l>cidit:S of puln1c..n:1i-y ;~:-Jq ..:::tq~is (;t-.lwsUJs!-.. budic.-~) in 1n:ltlTi<1.l {J~1::1incd Ly luI1g punctlll"C a11d in the ~-uutt1Il). J. /'1,tft. C j{,;r/., ?i2: 172, 1929. Cu,, c-;1:. S. }Z. Tl,c pn--cncc of ,,,b,stus !JLn in the lesions nf :islxsto., ,n,,k,:r,. Tn/,,.,rJ,,, 10: 404. 19'.''J. Sa\\ART. Jl. L, };1,c11u,, C. L. ;;nd C,11.1 .i,c,;, E. H. ,\,lKslo,is, l\,o c;isrs. . !,cf,. /'1111:., 12: 90'J, 1'J3 l. 27. \\'()UJl, \\'. B. ;,nd S:uiys1:. S. R. P11lJ11u1",r) a.-Lcc-,Iosis. Lr;,,rr!: 2: 1~8:\, 1')>4. 28. J.y,cctt, K. '.'.!. l'11lrJ1on:1ry .tc-1,c,lo.is. J .i. .\I . .l., 109: 194, 1'!36. 29. ~yn1p0:~iu111 on the. t1 e;\lnh'tH or chr,.-J\1;(" 1JtT} l!i11)\1 pc>isonin~ \\itli .\(:r11 :1ud cur~i'>t)IH' . . -!,(h. l11d::1f. lh,1.;., 3: 54:'>. 1'hl. 3U. H.-\.Lt)\,1.,) L. }Ji.I-'., (\J1.. 'J~":.\"-D, :'' aiid J-~HH,F.. !\',, I).\\., J1c Pul1nun.1ry in~1.1f1lcic Ky . 1. l'Jiy.,,iul.1:i- c:d rla--=sifiL-~l{i(Jn. dinic:d 1n,-t1od.,. of :1n.d;--.is. :-L1nd:1rd ,:dtH':-. in nu1 nLd '.--:.tt 1Jj,ct:-;. J/1-,/,:i',;,_,/' 1 7..~': 243, 1948. 31. B.,LD\\\,, D. lliF., Crny,.,,n, \. :-11,d /.!.,,;; ... :1Jc:. IJ. \\'., J1-c Pu)Jn(,u;1ry i11->11fFli< 11<.. y. 11. :\ :-:.tt1d~ CJ'.. thiny-ninc cas;cs of p1il111u11d1) fi'.;10:-i.s. Jf1d,,-111,. 28: 1, 1949. '>2. B,Ln.q:--;, E. Ui:f., Cnt:J(;{.>.:Sn . .\. ,md R,u, ''"'' ]). \\'.~ J1-<. PuJn1onary in5uif:< it~ncy. 111.. .-\ ~l.11'ly of 122 Ct\S.ts. of chronic ptdin, J11;1r;- c:ni il !~.--.,111:t. .\frr!lti11t. 28: 201, 1949. ,r.. c,.,.":. .,.... ,,. 33. ,\ts1R1,,c, R .. \lcC11.,n:;..:T,.l. H., l,:.,;;.1:in. ,\. ,l n":-.,,1.0. K. 1,111,,. R. L. ""d (:lillit-:d Jnd phy".--:io1o_~ic fr:ttll (.'-": <if .s11;~1.- 1)"/". ! r puln1on;-1r) disca-:cs \\'ith i1:1p:1'.n11. tit uf ~d\c,,:::: <apilLi:y diffu,ion .. lm . .J ..\f,d., 11: 66~', l'J",l. 34. LY:'\Cll. }-~- \L and S\1lTH 1 \\' -\, Pul;11,Jn.111, ash, ,<().;;i-:; UL C~1rcino1n,1. u. lun)~ in ;1.-.:\1i_<t ~ilicu.si~ .. 1...t. .J. C,n.(o, 2~: :;(1_. 19:;5_ 3). Ci OY.---.:L: S. R. r,,o l"~Lc.:. uf ~qt,;1111(1l:S c::t, !l) 1 1i'!"l: :1( the lun:'-! in ;,:;;.ht..:-.Iu.s;is. 'f'ul,drl 1-;: '.) _ 1<):::,.::,. 36. C10Y'\L, S. R ....\ C.-\:.:c or U.tt Cl}] l.;.:icin(1111:1 {' /l\ 1 L!~ occurrill.~ in ii.~,bc~.u,,o.:;i,. 1""zd:~, It,: 1~;: 1UU. )~fi.., ::.r_ 37. EcHYKT, J)~. S. ~1nd Ci rcr:r:, :\. J_ PtJ~1:tq1J;..,ry ::.__\w,;- tosis and cuclno;n~1. 1(~:p .1n of ;-, l-~~=--1-- \\itli nlcrop:<-y findil)~S. Am. Rn. ~'',tlillc., 3~1: 1-i~> 19~1G. 38. ?\'uKD\t.~~:--:, ~L I)er HcruL~n. h dLT .\~t)~:-stt)~.!'. h:t- l<T. 71,rhr. f. Rr,l,sfoi,r/1., 47 2SS. l 9:,8. 3'J. Js,cu1, K. !\f. and S\1t1H, \V. 1\. l'ul1t,tJ11 ,r\ asbe:-tosis. Y. :\ 1rpurt uf b101i-.h;;d c.1rc;i'.t 1 '' and epithelial mcupbsia. .-1m. ). C:.,,.rr,, 3(,: S67, 1939. 40. Ko1-:u;c11~ F. Lungcnhrd)s u 1d Bend. /.11.fu1.',I,/ G,,,.,-,/,,./1_1_,;., 27: 32, 1940. N (J V E M ]{ F. k ) 1 9 S 3 Asbestosis, l3ronchogcnic Cc1rcinoma--- Js.1c//){lc/ia el al. J.1,1.nAc.11, A. J. and \\'u>J.ER, H. \V. Asbestos und Lungcnkn:l;s. ,1rrh. J. j,ath. .11101., 307: 387, 1941. 4:!. N'ORD\l.,l'.N, M. and So1ua;, A. Lungcnkrcbs <lurch Asbeststaub im Ticrvcrsuch. Ztsdir. J. Krebs/orJch., S1: 168, 1941. 43. D1-.s,1EUJ.ES, R., RoussEAU, L., G1Roux, l'\1. and S1R01s, A. Amiantose ct cancers pulmonaircs. Lmal mid., 6: 97, 1941. 44. I-101.u:ll, H. and Asc1usT, A. Bronchogcnic carci- noma wit'h-pulmonary asbestosis. Am. J. Path., 18: 123, 1942. 45. \\'1-.01.ER, H. \V~ A~bcstos und Lun~c:nl-.rcb5. Drut,c/,r mrd. Wch,urhr., 69: 575, 1943; ab,t.-acted in: Rull. llyg., 19: 363, 1944. 46. HO\rnURGER, F. Coincicl<'ncc of primary carcinoma of lungs and pulmonary asbestosis. J\n,d)sis of litcratlll"C and report of thrC'c cases. A1:J. J. Path., 19: 797, 1943. 47. l,y:-,;cu, K. M. and C.As:-os, \-V. M. Asl.iestosis VI. Analysis of forty nccropsicd cases. Dis. Chest., 14: 874, 1948. 48. HuFPcR, \V. C. Environmental and occupational cancer. P11b. llcalth Rep., Supp. 209, 1948. 49. Ct:Rt:TON, F.. J. R. Squamous cc-II carcinoma occur- ring in asbc-.stosi~ of th1 lung. Brit. J. Caner,, 2: 249, 1948. 50. S,11111, L. Pnl't1moco11io;is and lung cancer. CQmj,ms. .\/rd., 2: 3, 1949. l~t. OwF-., T. K. Carcinoma and asbestosis of the lung: Rcp:1rt ofa case-. I',,it. J. Ca11crr, 5: 382, 1951. 52. S101.L, R., B.,ss, R. and .-\:-.GRIST, :\. A. .\slxstosis as,oriat,d with brunclio;;enic carcinoma. .-t,c/1. Int..\J,d., 88: 831, 1951. 53. Ht, l'ER, \\'. C. En,ironmental lung cancer. fodurt. ,\!rd., 20: 49, 1951. 54. Rc-gi,trar-Gcneral. Sutistical Rn icw of f.ngland and \\"al<-s fnr the Year 1948. London, 1950. H . .\l. Statio:ie, y Offict'. 55. Report: :\liner, Phtl,i,is :\kdical Bmc-au. Unio,1 of South .-\frica, Pretoria, 1936. 56. K1.0Tz, ~1. 0 ..\s<oci:1tion of ~ilicosis and carcinoma of lung. Am. J. Ca1:.-rr, 35: 38, 1939. 57. L11rn,i,;,,r:, G. F. :rnd BL00,1t:R, \\'. D. Brnnch0gcnic cardi:oma. Ca11a1, 1: 234, 1948. 58. \\'1LL1s, R. A. Pathology of Tumors. St. Louis, 1948. C. V . .\fo::by Co. 59. I.1-..D<;:oG, G. F. Brondwgc:nic- carcinoma. .-11111. Su,g . 124: 667, 1946. i \ \ { ' I I I rap,11 cnt pritll,H; n;u-y d granult pncu111di:.t:i!SC groups SOll1('\\ gcne1 , matte1 abanJ ?, 1is~o-: dust ir dust f old cl -~pi<>CO' tower Ill ar. said 1 Th gripr a di appr and: bc 51 proll 1110n sist<:: chc, fil tr: rem dn, C\111 SC\"( 1 def fine on< AMERICAS JOURJ'\ ... L OF ME!l!CINE