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-- 1. a v_ Jou N r >: * <w y v ngianc 7 Uirar; .V* iUlU nai1__DGr_.a_i~yieG"! * icme ovoTn ' 't;j:rjsKEo by the Massachusetts 'rs.v.oi. society >U.:M 263 OCTOBER 12, 1961 NUMBER Ij ' OrijjinaJ Articles rvrntivc EiTcets of Tsoniudd in the Treatment of Primary Tuberculosis in Children . . . Prank W`. 'Mount and Skirley tf. Ferebf *13 :pericncc with Portacaval Shunt (or Portal Hypertension......................................................... "21 ('torge . Want: and Mary .-inn Pa.nt icration of Blood on Storage: Measurement- of Adhesiveness r.( "\Rins" Platelets and Leuko cytes and Their Removal by filtration . - Roy L. Sxank "23 <tontie>n of Kidney Fimcrion by Splenorenal Arters.il Anastomosis: Report ot a Case . . 734 '-`*i\y M Seikley ' M&ikai Pn>gr*<s :utr Glomerulonephritis vConclu:! d) . . Jerome P. rCuxtrer and Wlliient &. Schicart: 736 Medicai Intelligence Salvage of the N'car-Tran'metacarpal Amputation Stephen W. Meagher Isolation of Vaccinia Virus and Type 1 Adenovirus from Urine................................................................ ion Crasser ana Sidney Kibnek Current Concepts fa l.empy: The Treatment of Hyperthyroidism.................................................... E. M. Chapman 743 744 Ci>e Records of the Massachusetts Ethical Drugs r riitorials Generic -Names, Trademark* and "Physicians for the Futurr* -- /Joys of OYrtrn . . /j< 757 *svrhu-Mtt* Society asaches#tts Department nt Pehite JTewlth Notice* . 733 733 3C<orerkt-- ti*woenv<lvirendr* :ki JSS?1 wn, you '-3' ! " 1(*0>3<9<iieottt -<in ,i-- MitnaiK*iarursMieMrrirrt mm in -::::9ZZ% . - ' * 38 omfltmi Atiit* Oiwmecceews f**r>nettt ' 883R *- JT7 .* T' Ilosone' wor ks 'Sscto*j t -- 93-315 - ~-*'T ' . HeittMt to soeed tv- |-.j,-. I --. ! :r.. I - U1'. ...hm w ------------------ r~|--r _r ci^-.S3.S% 4.- recovery `(MrMCM , 'MMA i The usual dosage for infants and children under twenty-five pounds is 5 mg. per pound every six hours; for children twenty-five to fifty pounds, 125 mg. every six hours. For adults and children over fifty pounds, :he usuai dosage is 250 mg. every six hours. gg In mure severe or deep-seated infections, these dosages may be doubled. t\i Aeailoiu- ax: Puivuies*--12S and 250 mg. t; Oral Suspension--125 mg. t per S-ce, 3 teaspoonx.il; ans Drops--5 mg. t per drop. Product brochure available; write Eli Lilly and Company, Indianapolis 5, Indiana. "oowa (erasiew >3 ? MVIIIIMI S3 !* lawivi uilat*. UIItI 7).i '/ .W. * i: 1 i s I t; >1 5 5 1 3' ! \ i \! i ' ; J . ill 4 \t Ii ij C.\* ` **\1';* ' `I'HE `.!.\SSAC,:*"v"T'rt. \t H06FI i ;n ci'-ncii' on the :ror.i;:i'"". <. w.:n :..c u .. ..:gero*n! f . crtliy.-oid: .. " ::ildr . - t*sc at any age having irenr.-T.t di.-cus*- uurir.:* .regnant... rrrrun factor' -.u b* ;nus operation often insist on radioncth ' ceptru cs an :nd:c...:on for ;unrotal :i:y.- :dcc:-mv. S-'inc at an;. *cc from fear of radiation ind.-i Toxic re.-n -o drug therapy, rciap*- after re- :c?c treatment. IVw rufients scem-anxiouv --nv--*-- . -iged drug therapy, progressive en- loionged or repeated courses of drug therapy, iarttement .f the goiter under rruuirni treatment and aatients in this group are often restive and psychic factors in the patient or family that rcr.u. r operative in a successful therapeutic program. medical :hcrnp\ Inr herd .:rr each indications for >:ch the fetal uptake of radioactive iodine operation. T;:.' and safer- operative treatment 'gin until the fourth m..-nth of pvecnancy. [ after proper preparation wim .uv.hhyroid mea< ->< ; advise this treatment during pr<`ur:;mry at;d has decreased the incidence of f-. -.rspiicntiott* nebbed agnimt its use in those boiow a pre- very low level and ! '-'red the time required .. v.r.e : *-*n Hi'crmse of possible genetic damn-ce. hospital :r< an average of on:- week. Tine sk.d u; me ...... : llmii* h.ive varied since some age tv- individua. surgeon remains the decisive factor in u rri* introduced in 1944. At first, it was up reduction of complications, and so it is that '.by. years: more recently, it has been reduced roidectomv is no longer the province of the "generar* forty to twenty-five yean. However, the num* surgeon but should be performed by one espcci.dlv f citiidrcn treated individual physicians is trained in thyroid surgery. inir .1 'itrnincant group, for observation on the " iTccts of radiation. The late efTcets of this (Tn 'rmtinued) .=n will hi* wealed in time, but so far. '.he oc- R; rrttEXCZS ii occurrence of nodules of regenerative hyper<t adenomas has been most significant. .;h\nri drugs have the most important role in !. White. W. H. On t '(eenear* n-mptutm n{ rvi;lnii.iimic otrer. 3rti. M. ]. 2;13MI3. UUUt. 2. Gunman. E. and Mi: *.f. I Ci*rrr <-r:mam!---->. n( rirrrrtijrrotqst^ \'rt* Kit J. M.d. ZS4:i.*, i:*36. b CASE RECORDS OF THE SACHUSETTS GENERAL HOSPITAL Weekly Cinicopathologicsi Exercises "ou.voeo ;y vsha*o iasot S"v;.\:.un Castlemax, M.3.. Editor Betty U. Kieses. Assistant Editor CASE 73-1963 Presentation of Case trimissinn. A fifty-one-year-old man entered jitai because, of -leiV-ided picur.tic .-nest pain ' twelve hours' duration. . reviousiv he was admitted to the r.os.tu.h* ..f pneumonia of the upper lobe of the ng. At the time of discharge the x-ray films 't were nonnal except for a small rcsiau.-.. picuraJ effusion on the right side frig. ! '. . dr was well until the onset of the pw -;;t \c j.ad .ac: :..anv occupations, including work liioistercr anc in a siauehterr.r : .. P-'vrinninff nineteen yc^*s befoiv entry he worked for five years in confined spaces in the holds of ships, where he was exposed to dust and asbestos. On admission the \uicnt was acutely ill. with a temperature of 104'" v'. and bens of pneumonia in the upper lobe of :: left lung. X-ray films of the chest -'Fig. 21 dc-uousirareb complete opacification of the ieu-upper-lung iteid; the trachea was devi ated to the left- Penicillin, streptomycin and chlor amphenicol were given, and he began :o respond by the fourth hospital u.'.v. Sputum cultures grew out coiiiorro and protetj*. - mnisms, and a subsequent cuirure dcmon>tratet. rnedlllncierb organisms. A tu berculin skin t"'t was negative. On die eighth hospital day the fever rrcurred, and Staphylococcus aureus was recovered from a sputum 'uiturc. With sodium methiriliin {Stani'vhhn merany the pat:^*nt im proved. Serial x-r:t\ :d:ns of the ci---1 rc.-r-h-rj ,t progressive but inccmp.ecc reduction :n '-uumc of density in the left-uppcr-iung fluid. A film taken on the twor.ry.finc hospita: day frig. 3; demonstrated a cen;:.i.. rarefied area within the left apicai density that had a sharply defined inferif-r :::ar?in and pe ripheral air pockets. He w.is discharw^d unproved on* the thirtieth iiospita: day. Second n-itniisioti -two weeks later). In the in- crim tlu patient experienced persistent weakness, unsteadiness ana anorexia, although he c..inrd .) pounds in weigh:. No productive ch::!> < fever occurrec. X-ray dims of the <du**.t five o.;.- before admission again demonstrated .. .urze density orrr.rr.nn^ the 'V'"'*- ---- ` 746 THE NEW ENOE.^Wj* jV.1 * - ' 14 ,:~Z* ft*' w, . .?. *w*. - iiT-1 -T"~nr Fsoure I. Film of the Cl.*-: Taken Six Years before Ad mission. Showing a L*-euiuted Ptenral Effusion at the Jlipht-Lung Base,, .1 -til an Area of Pneumonitis m the Upper Lobe. ",,A.- "' . - FiiSUiit j. Detail f:on: v . Film >( '.u Ck< fining an Area of C ntrui : imtufenev in :he !./ V% ~ Suggest/?e of Loculared J-y-......or P'.emui 1 along the J.aii-'ui Chest Wall. > JS - Vf.v Ficvr.t J. ri'i'm <>/ /< > asst V ...* en : :'! Att::.. .s/iourm- Ova ,:-n of f/* L+fl (. : /<<.' /.,,>. thoras. with marked deviation of the trachea to i.;v left: .-nsidernbie io>> .! win-:v.-i me left upix*:' lobe. . ovation of ti:<- .oft hiius. d;iai-::on of bioncni and ;.:A Sbrotic changes were ooserwd ' .'.;cul examination . .-.dod a wo:! :.yu;- S'w.ciu.' ' - .. ,.:h sound: :hrot:y-.eu. the c: . .. .\ Urac<* . the aj.i' * no at-... - .. ...... The temperature, pui.se and /esphatium ' m;*l. The biood pressure wu*. !3j systolic. oj dl *1 urine was normal. Examination of tia revealed a hemoeiooin of 13.6 gm. per 1U0 hematocrit of 37 per cent and a whiuwei! c 7400. The pro'hrombin conn-rtf was ;'w` >* The fasting glucose was the htiuooin and the urea nitrogen 12 me. per iOu ml. T. line phosphatase was 3.2 Wodanskv units. . cepnaiin rioccuiation was negative in foiry-cigr The amylase was 9 Russell units. A 5ipoi s: raw a nt-viutw cruaiac test. A brop.eho'Couii u;..".(u: ivum .. :na:I.od inii.mmtatton and e-. . \ Mihceoi tnc d-p...;;:;rt*r-:ob' :i*ociius. A I v'.uu dc'.tionsua.. - hiiiue oi <<iisur\ i < :::r ieii upj^er lobe. . r. n.i> r .-.ue ! lion: tite wttuhera; braneues did i An .tcraiii :i was pertormed on i!.r id: dav. Du - r.;. i-vnAi DlACNOstsv Hsu:n S. Pit- wim -merrd *. : We haw the pi 'dial ait-.- ' z >`ui CAST ' THJv M ' SAC7IW.77S J-ACKAw HOS?r \l. ' ::-s. ; i: :por*ant poir.t* are br'Migh. : p-.tNt iu'- -v. ' ; years prcvv* :;v n?.*v ,ir. ".i'ijijs1 :sii?! i.-.c: a rrsts...tu * v;ur.. >n the right >idc whr. discharged. There _> *n of the rnditio:. -*f tJie left lung at that know that lie was then weii lor six years, i rotation ot interest is the occupational .iiich included five years of work in the ups. as well as employ-mem as an U;'n*;'terrr ianghterhousc at unknown tunes. nokir.M ,-)t the x-ray alms I ^nutlri iike to v ahotit rite first admission. The physical strd pneumonia with an open bronchus, and vonhy that the trachea was described as oward the lesion instead at away from it. rhnt the pneutnonia was superimposed on in a redueed volume from a pre-existing he <ame urea. The acute process responded ;n tiu* three antibiotics that were given iv pending the .epons ot the cultures. Hinder organisms were probably the im- and t suspect that t!v*y were present i.s<*u although not cultured until the second * t ilAt cite consolidation was apparently '-tent with FriecHinder's pneumonia. x perimposed upon an underlying proc- i^xr significant finding was the culture u>h. (tuii'us, perhaps secondary ro the anti- py. Either ti.r Fricdliinder or the staphy- ranisrns could have produced the rarefied no air pockets that were visible on the day. Now, may we see the x-ray films? u:d L. Weber: The films of the chest ars before admission f'Fig. 1) demonstrate a in rile upper and middle ficids of die `.nuMsicnt wi pneumonia and a pieural icn cieared with the exception of a small ight cotopi.renic angie. On an cxaniiaa- 1*2rs iatcr tlicre is no evidence of pncti- :nc obliteration of die right cosrophrenic present. :\n: Are die lungs entirely dear ru'ar the V<-<. On the first examination during iihio? -rig. 2' one can see a homo;irv ailing the upper chest cavity on the iterating the mediastinal border and ex.ie laierai chest wail. The inferior border d dinrply defined. The Ur/-. ;ulus is not there is no evidence of a mass in that r-lung firid and die right-lung fieid u opinion, the trachea is only slightly ie left. The visualized rih structures are ' hm t;uten right days later <now mul .i translucent areas within the previtrated homogeneous density, which bar red. A faiiiv homogeneous density is dong the ieft lateral chest wall. ;hTT*.\.v: T< that `isistcn; with Dr. 'A'l.ai-.R: I. eompa::* '* lncu!ated fluid in the upper du.-. cavity. Tk. amination per- ..formed -Ajew davs !a_a. how\ an increase the translucent area* in i:;e upper-lung field am! again the presumed fin id ai^ng the left up -or ch">t wail, with streaky dcnri.k" in the lower-.;.ig field that might be atelectruu .rvn.*. Dr. Pittman *. There aofinitdv is t-*m a pronounced deviation of the trachea toward the icsion. as I as sumed from the mx-.-iption. Dr. W>.r.F.jt: The patient had a slight scoliosis :>f the upper dorsal spine, w-.iii a comexity i.i the left contributing to deviatio?* f the trachea. Also, if one examines, the films in *-..vnee one nntires a slight deviadon that deveioprt. during the course ef the illness. Dr. Pittman: However, it doesn't imply the pre existing reduction in volume of the upper-lung field pulling the trachea over fiui: 1 had anticipated. Dr. Weser; The final examination (Fig. 3} dem onstrates more clearing or more transiucency in the homogeneous density in the upper umg. with persist ence of the nomogeneous density along the left up per chest wall, which is compatible with pleural fluid or perhaps pleural thickening. In iidbuior. to the conventional ex.-whnatiom 1am- inagraphic and bronciv-irapnic studios were per formed. Alrhougi: :hc u.v.chngram is inadequate, the trsr!ua. left-main--mu bronchus and the pri-uan* bronchi are well -down, and an intrinsic le sion is not evident. Titer*' is slight rievatinn ot tnc left-main--.etn brotu'aus. consistent with reduction in the volume of the left upper lobe. Dr. Pittman: Therefore, on the firv of the tw recent arimi'riou.s I assume that this nan had pneu monia. prooaoiy due to Friediancictb organisms with a superimposed stapnyAcoccni infection. When he left the hospital lie was not well, hut improved, and nine days after discharge v-my films mowed a large density peripherally, with io* of volume and eleva tion of the hilus. that wa- probable a p.; ;ral rather man an mtrnuuimonar- process. 'V> now have to consider ute syrurxoms .;;u 'igns in addition to the ennnees demonstrated radtologically that i>*d to the second admission. They were predominantly weak ness, unsteadiness, anorexia and -i heart murmur. The absence of a productive cough megests that thr proc ess that was present at that time did not communicate with die bronchuv and now that l have scon the. x-rav films I a: * u\inccd that it "as in the pleural cavity, anvwav. i uvre were no signs of nb*trt:rrion un bronchoscopic exanunation. svhich diowei; :m*:viy in flammatory changes. Tfive only abnormal laboratory finding was a minimally elevated bilirubin of l.' mg. ver 100 mi. The choice oj tests performed >uggest* that i;:: attending puysiciari.s had in mind a lesion in <! --- - --- US THE NEW ENGLAND JOURNAL OF MEDICINE Oct. 12. What processes must I consider In this case? Since the available data are sparse, I am trying not to neglect even the smallest hint In the information given to us. I shall rur. quickly through the pos sibilities that I considered before seeing the x-ray films because they no longer seem relevant. I thought of an ah uolar-celL. carcinoma, which__can produce fibrosis, but I was overemphasizing the tracheal de viation. Profuse sputum is usually a manifestation of that type of cancer, and tin* involvement frequently is bilateral. This man had a process six yean before admission and a recent process that was comparable in many respects, but the fust one cleared completely, and it seems unnecessary to look for an underlying, tong standing neoplasm. The lesion was not suggestive of adenocarcinoma, which is a peripheral process, and it bore no resemblance to a metastatic carcinoma, die suspicion of which, was apparently the motive for tiie tests of liver function and the amylase determina tion. Certainly, tuberculous could produce this pic ture, and the negative tuberculin test doesn't exclude it. but it does make it less likely. There wu< nothing to suggest sarcoidosis. Having di.-wmded thoxc entities, I turn to a consideration of the patient's varied occupational history, beginnhig with the hazards that he may. have encountered from industiial dusts. He was ex posed u? asbestos a number ot years before entry. Asbestosis is a form of silicosis, and whether or not asbestos gets into the ah. -on depends upon the par- tide size. I: is my undemanding that the particles that arc encountered during handling of the manu factured product arc too large to reach the alveoli. It is when one works in the asbestos industry itself that die dust exposure is dangerous ;:nd I'm going to rule out the holds of ships as resra/ds a diagno sis of asbestosis. ' Another perdnem pneumoconiosis is byssinosis. which is produced by cotton dust. That seems the most likely hurni'ul agent that he might nave bean exposed tc> durintr his care--- as an up holsterer, but ausin the particle sice wcuid have been too larse. and that condition !>n't sucsested bv -.his V* * picture. The question of infection rcl-ted to his cu nation ari^-* next. Admittedly, his occupation may have had nothing to do iih this illness, but I have to me the few tUL'.s g:ve:t in search oi a clue. Fungous infection?. :..uy he associated with many types of dust, and one uut l mink o: particularly is histo plasmosis. I don't be" * e time poultry is killed in Slaughterhouses. ana d . .. merely touch on tiiat diag nosis and discard it. ` -topiuj-?nosis can be respon sible I-.;: bbrodc peripr...-: ai nta^.es and tan induce cavitation, but otherwise ir.-v Tv-dings in this case .-mblance m it. Thor- .i;<: other fungi- hut :-'<r to take the tiir-i even to name them. An. . ...... v.jrhous* drier.*- thr.` ` shall n.-f.--.n in 'u.-.'i.:.. ri Hll rabbits i' . :.d . roduce abscess cavi'b-s that persist for months and can can pleural effusion.'*' I have come down the list to one other, more mon and to my mind much more logical disease a slaughterhouse worker might have. He .nay h: infected large animals, including swine, and : thinking now of brucellosis, which can cause ch pulmonary lesions and effusions; It is manifest, many systemic symptoms, and in working with meager history I cannot neglect the weakness unsteadiness that this man experienced and the diac murmur because brucellosis can produce t carditis and can cause murmurs without recog endocarditis.5 I find this the least unlikely cxplan of tiie patient's illness, both past and present. T fore, I shall say that he had on the firs; recent a; sion an acute lel't-uopcr-lobc pneumonia, pro due to Fricdiiincer's organisms with a superim: Stapit. aureus infection, and that that conduioi cured. In addition, I am going to accuse hi having chronic brucellosis, probably acquired infected swine while working in a slaughterhouse haps first manifested six years ago by die proc the right lung and currently pi-.-during elT fibrosis and possibiy some granulomas in the >e:t with a systemic reaction. ! ku Lawis W. Kane: Was dtis man m aicoi Dr. John H. Kxcwlss: No, lie ua< not. Dr. Benjamin Caetleman: Why du you av Dr. Kax::: This story is perfectly cur-i.stent multiple aspirations of saliva producing infeed die riffht lung originally and subsequently inn and ,, iung abscess on the left side. The n:i types oi organism in the cultures v;ppor: that nosis. I tiiink that the patient riuli-,1 up v.! empyema as well as a lung aiiv.-i-s> <>m the ha aspiiation o: contaminated material. Dh. Samvel Thier: I might add that bewa. epigastric pain and vomiting an upper eustroinu scries was cone during the first recent admissin was '-ormai. The question o' aspiration pnem was .-juddered. Aio observed at dun ti::v.* w: treme iettkopenia, which was tiie reason :' u-i-e with so many antibiotics while we u- -rv: decipher the cultures. The wime-erii co-.m \ the range of 2000. and this was ..::e of ae-. <-.ai ineumon.T oroc<- .wcomtAwned bv leu.v*vc::: r* had seen wit. .a tiie last few months. Dr. Warren Point: Dr. Pittman, do I unde you to iinpri that the pneumonia was basiea. dttced by SuecD-sis. or do y'u: think dun tin* l !o$is was s:-* h another inf- concur* cut w! e;ear-cut die pneumonia.-1 L'R. Pittv * I am <;.g*resung iti uiv fantast: he .. ' "... . edaSLS. .. ' \\do vou have :* brine thu. xniam eov.r..:ve -:*n. he v.. - . ^.uugiuc \% orker ' anti. r\$z Rr.CGivi> .)F -`-nc r-s gkattm ?u-v *O :'TMaN i i don't --* - ust Citi. . (Vi.: If t];i. was F.-k'dlKru!-: A pneumonia. ,::'i .- expcr- ...* ;obc to be iargcr aoiu- . with bulging downward. :r than ti:e mnikcci reduction in voiuni'.':* x, Pittman: I wouid. and that is whv. .i< i load .! record. I thought that th.- lung was rhc site .rvinu* change because of the r.catcd ir-mrion riatior. of the trachea. A chr.inimiiy seanvc: iooe reduced volume seemed th': only way m account : superimposed pneumonia and deviation of the .a unvard the involved area. I explained the mrour that was shown on the x-riv. aim :r nasis of hn increase in sire of a portion of lung conic: still expand. Kant.: What operation do you think was per* rri? x. Pittman: Previously, I believed that it was a '.cotomv because from the description of the x-r.w I c::tir:`.` expect an effusion and had in mind ;on of an area of residual pneumonitis or possibly muiomatous lesion. I now suspect 'hat the snr- opened the chest to drain an -:;npyc:na. \rlp. M. Chatman: Or.c occupational dis- '* you didn't mention i< so-called metal-fume . v .h is bclievevi co be allied to zinc and other i products. Such fumes arc chai.utteristicaily i in confined spaces in the holds of ships, and the >e prooahiy results from fine mrtai fragments that -gc the invg difTuseiy. That condition might formed a background in this case for the suosc* : bacicri.il infection, whatever it was. . Pittman: This patient last worked in the of 'hips fourteen years before these admissions. .. Chapman : I am speculating that the back- id was scairing of the it.:-; from fine metal par* :: -i he inhaled in those confined areas. . CASTLr.MA.v: What was the thinking on the > Ttnr.R: C"r initiai impression was that rhc tntgr.t ho . pneumonia. with the formation of a :b<rr*5. perhaps seconder/ to obstruction behind >piasm. and he was treated on that premise. 'urpoK' of the operation was to find out whether s a tumor and, if not. perhaps to resort the ved lung tissue. PVTHOLOCILAJ. 0: Dr. Ca-ti.f.m.,:.-: When . *.;r_ - ' : : u. patient's cites: .he found no fluid. The ' uppr? lobe .svas bound d-wr. '_i;e chest wail, and it was r.---;* sary to cmpl." to dissect the adherent vi* . d from :i a p;.r:e:..i pieur. which was extraord:;-.. :. thick. T'tfC j;'i? uper Ive had shrunk into an o* - .o mass, about 12 by 0 by cm., reminding the surgne. of the -i/c and .shape of a tangerine. T:.r dl-oa :cl no* in* - ivr the lingula of the upper lobe, !**? > wrciy die ups.rr segment. ..r.c! he was able to divret i; free from ti.r iinguii. which was expanded at tint rime of operation. Since the n-scctcd segment was hard and hbrotic, hr hciievrd that Iv* was dealing with a chronic pneuroeruis rathor than a tumor. On section the pleura was extremely thick, hyalin- ized and acclhd.tr. and it was obvious why :ite surgeon had difficulty in dissecting it. This is not the usual finding in chronic pneumonitis, even with extensive pleuritis. I think the area on the x-ray films that suggested iocnii/*-.! nv.pycma or fluid was the thick ened pieum. w-.ich in places measured almost 3 cm. Micros^opicaiiv. there was marked fibrosis obliterat ing portions of cite ring parenchyma. Section of another area showed vory severe, rhronic purumo- nitis. with cxtjdi.-.te in .-ome of the air spaces and marked chronic inflammation, including the phago cytes filled with lipid that one expert.' with any long standing, chronic nr.p-imr.mtis (Fig. 4'-. Cunical Diagnosis oneumonia. ? carcincm..'.. left upper lobe. ` wr. Helen o. Pittman's Ducnoses ohic .. .iccilosh with norosis. left ring, oral effusion. :o:b.. mnonia. acute, left upper iohe. prri-a'oly dto Fricdiander'* organisms, with sureri:npr<-d s//r *iA i.... ~..--J _ rto.uxe r. Chrtjnie PneumwiU'. The aivtolar xax/* ere tr.:ck/ied: the an rccs an `-..led } II (i II fi , * j l ;| ii l: i .i j ! t 750 THE NEW ENGLAND JOURNAL OF MEDICINE Oct. 12. Dk. Pittman: Can these changes occur during a $ix*wck course of illness? Dk. Cas*j !.M.\.\: I think they could, but in this case the background was probably much older than six weeks. Of course, we don't have a him taken during the* tluve y^ars bcfoie admission. but 1 ana sure dun something had been e* -.eg on for a matter of months, periupi even a vent. Careful examination of die air spaces under the microscope showed a r.ttmber of brown, irregular bodies with a knob at each end. characteristic of the clubbing and the irreeul.nhv of asbestos bodies (Fig. 5;. The fiber is in the center and !.* covered with protein, which then degenerates slightly to cause the irreguiarm. Aabcsto* bodies stain brown because oi the impregnation with iron that occurs in their forma* tion. Therefore, tite underlying disease in tliis case was almost certainly asbestosis. Some authorities' be lieve that symptoms and >i^ns and j pneumonitis arise only when a secondary' infection is superimposed on the pre-existing asbestos libers -- that the asbestos fibers are fairiv inert, but when a secondary infection intervenes pneumonitis nut develop. Thickening of u.e pleura (Fig. b is typical of asbestosis, and, in fact, a anthologist with ^ experience with the dis ease immediately thinks asbestosis when he sees that change. There were no metnplastic changes of the bronchi suegr-ting that a tumor war. ffeinu formed in this case, and we made a careful search because asbestosis :s one of ti.*- predisposing .wctor* for carci noma of the lung. Dr. Pittman: The findings interest me very u because from nay reading and from what l hate h Dr. Harriet L. Hardy say repeatedly, asbestosis d ops only after exposure to minute particles of a>l less than :J and no more than 10 micra in six didn't think that it was possible to contract the di: merely from applying asbestos in preparation anc dealing with die dust of the mining of asbestos. Da. Castleman:- Of course, the disease de\eK several years ago, when the hazards e%en in the of a ship were probably far greater than the\ are : when more precautions are taken. . Dk. Kane; The patient did have a lung aba didn't he? Dr. Cattleman : There was no evidence of a abscras at die time of open tion. He must have an infection in the lung tiiat shrank, but .ill our : ings can be explained by secondary infection o underlying asbestosis. Dr. Knowles : Dr. Castlemau, I don't n understand how you can relate the cxjoosurt asbestos to this man's recent illness. How can associate a localized disease in one little part of !un with the coin-, identa! fmdins of asbestos fin Dk. Ca> i undoubted.'-/. : He :..d die asbestos fibers Dr. Knowlee : But he had had those for nine years. Dk. Ha.stleman: Tliat's rii:i. and then a vcc ary infection developed in die left upper lobe. * 1 * . A* :Sat.v - Ficcsi. ;. mir'ioui Aibti Area. Ficuur 5. A. riu and Tkickenin.' X28) u., ?!t V U\4t RF.'.ORDS >F TIL VtA.'-ACHUS'. '/:tai. -m-LK- So tin . < . necessarily and slow. si,.- resp::': ' >r.. - . in..;:u .\a ru^D . out a ' ovonir orgnu:-* pi (he hospi-.;. vm- r.g or c.inrrher. -id occur:-.- i<%: ,t t * ?.* > on arrival rescaled a wcii < S-.-sTimposed on the a*i'estosi.s. ci' doped. u^:i non.-*1 d infant to appeared hvpr- te'tion is whethnr liic infection would haye_ ...thermic .;m. vus -y.m `tic and withrvr, respiration. ;ed without the asbestosis. `!:o fyi*N .*.:.d fontan'-- were sunken. The nose and Kx*wi.r' The x-ray films show only one wv;c normal. N- heart rounds were audible. on of pi'-ural thickening, and I find it difficult T:.t* edge of t!:-.- b-.er was palpable 2 cm. below the ain. even tiiough it was marked, the localized ' right costal margin. thickening, particularly in ar. upper lobe, on of j.-he'stosis. which ordinarily produce? .! lowm-lnint changes and !ower-!obe pieurn: The h^art rate. was i"< .ifter artificial respiration was instituted. While oxy-.cm was administered w.A-t pressure thro>;c.-. an endotracheal tube. iniro* U:g. .'A.stlfman : It isn't necessarily bilateral. Pittma.x:' How do-you explain the complete cardiac epinephrine was given, and a r-i'down for iiuravcnous-rhtiri -.{-.crapy was performed. After a mw minutes the baby became pink, and rhe pulse st mi. ; of the comparable process on the right side iizrd at a rate of 100 to I2i per jumuie. Spontaneou* before admission? Thi? man must also nave lcstosis in the right lung at that time, and yet it without tiie development of thick plcuritis. respiration began, he erica loudly, and good move ments of all extremiti'-' were seen. The lung* were clear. A cruticni macular erythematous *kiu eruption ' \srLKMA.x: It probably was a less sev-uc was observed. The imravirnous-fiuiri rhernuv initially !i consisted of ia mi. of mi line solution followed by 1 gm. of aibumin. Subsequently. a mr.Itipie electrolyte, A.XATOMICAL DlACXOS&S potassium-containing solution was im-i^ed. to winch put uivnntd<! and marked plcuritis, left l>*r lobe. ( chloramphenicol, rvyuiromycin ami ;.:cv digoxits me, 20 mg. ot cortisoj hctnisuccinatr were added. During the next four hours breathing stopped twice. Ti;* first time, tr-uscitativc measures were .successful lu Rf.FEREXCES 1 .i.:. <ri*'ininwrt. 1'ilar^mi.i: //. ZS ; '2 rW9 I**..', : r.iiarenne I'npumnnsa J.A.M.A. JOT: liT*110. I?36. \ U TU, y*tutr tt! ,'ii uerllniii. 4+* jjp. Minnranoii** \lmnrij P-r" ! . '.in Kr^nic/J*"m*/"h. wAi.. OE.ditPt^athboyiotfv o]t. pnK*i*nym.oeaonndin*Cw.. MIn. t~'x` :>t>. .'ion title, omwn. {&UJ. Cltatitrr 2. P. 32. restoring spontaneous respiration. The second time, during an hour and a half of assisted breathing, the. heart rate gram.*!!> decreased. The child died four and a half hours after admission. DlFTERE.NTIAL DtAONOMS Dr. Nath : R. Talbot*: la tin- rase one ran only -.mess the .hoiogicni diagnosis. Rather than trv to catalogue ail the conditions tlsat might have caused CASE 74-1961 tills child's exitus. I prefer to focus intention on the most common causes of this type of problem. In re Prescxtatiox of Case viewing v. hat little information we .have 1 notice that the mother had endometritis, and it would be inter A-weck-oi': male infant was admitted :o the because of rapid deterioration, i'.iiti was the product of a normal third pregnci deiivfx-. except that the mother was said iiad endometritis with a temperature of a few days after delivery'. The birth weight ounds. 14 ounces. The nconacai --xaminarion : a husky, biond infant, with a vigorous cn' evident abnormalities. He fed well and pounds. !0 ounces, when discharged on the turn uuv. He progressed normally umii R^iore entn*. when his nurse noted that he 10 p.m. and 2 a.m. .`'edings pooriy. Although by his condition m 6 a.::;, on rhe fifteenth fe. she delayed coiling the mother until 7 a.m. esting to know whether :i:~ placenta of this pregnancy was examined since the microscopical examination ef the placenta may reveal infection that can lie riiarrd by the baby. Dr. Jojix S. Robey: A fro7cn-sec::on cxarrsir.a. tion wasn't done, hut the. placenta was grossly noii'.ia!. Dr. Talbot: `Pnis baby wn> fairly iarge at oinh. Was the mother diabetic by my chance? Dr. Robey: No. Dr. Talbot: If the chiid had a h.,od incom patibility we wouici have been informed of it. I must proceed on the assumption that he was annarrmiv ail right until fourteen day? of age. Tbi' the .ige when congenital malformations and inborn errors are often detected, and one also thinks of trauma and *?" tiicr summoned.a p.oriinxrician. who found the >oriy responsive, with sunken eves, poor coior Aetiiif chief. Ch''dren') Medical Service. M.i*aeii:-4*tu >: Hotmrai: utociate prei--^or ai pediames. Harvare Medw^. Srhnnl. ^ No. 14 CAii RCORDS Or THE MASSACHUSETTS r.NKRAL IIOSHTAL 747 CASH RECORDS OF THE ' ssachvsetts general hospital Weekly CHnfcopathoIogicai Exercises fOUNDtO BY JUCKAXD C. CAUOT * 3e.vja.min CastlejiaJ1?, M.D., Editor 3etty U. XiBBEE, Assistant Editor CASE 62-1963 Presentation of Case :;ty-six-year-old plumber was admitted to the a? because of pain in the chest. tient had been in good health until twenty- ^ previously, when he began to experience idea chest pain. Six months later he was told i x-ray film of the chest* was abnormal. Twelve 1 * 1 .% , because of persistent chest pain accompanied ;pnea and a cough productive of white spuTh ere had been no chills, fever, weight loss igue. A tuberculin skin test (second-strength was reported as strongiy positive, but studies of turn.and gastric washings for tuberculosis were e. X-ray films of the chest demonstrated a ! density on the righr side, which was thought resent partially organized hydrothorax; bronpic and bronchogrnphic studies were negative. >ided exploratory thoracotomy was performed, ccortication of. the pleura; the pathological di- was "dense fibrotic pieuritis." He was disd home on isoniazid, 100 mg. three times daily. months after discharge the patient re-entered rsc hospital because of continuing chest pain, had not been improved by nerve block per- in a surgeon's office. An x-ray film of the .veaied thickening of die apical pleura on the - ~od a nncar'densTtyoverlying the diaphragm die left cardiac border; 'on the right side nogcncous shadow compressed the lung ard and medially and extended from the > die level ofi the second rib; another density d from the third costal interspace to the dtaThe fourth, fifth and sixth intercostal nerves < 'fieri in r.n attempt to relieve the pain, and v < \w....n.uii-o of a sprciimm of the pleura re relieved by the operation, and he was referred to a psychiatrist for further evaluation and treatment. Two weeks before admission he entered a mental hos pital for management of depression. Anisocoria was observed on admission. An x-ray film of the chest showed a decrease in volume of the right hemithorax, with partial collapse of the right lung, pleural elu sion, shift of the mediastinum to the right and an extensive density in the right-middle-lung field. Transfer to this hospital was arranged. Bilateral nerve deafness had been present for sev enteen years. The patient had worked as a plumber for forty years, having spent about half of that period Installing insulation on boilers and pipes. He had smoked V/t packages of cigarettes daily for many years. Five years previously x-ray films were inter preted as showing a peptic ulcer. There had been a loss of 30 pounds in weight during the three months before entry. * Physical examination disclosed a pleasant man who did. not appear depressed. A right-sided Hor ner syndrome and drooping of the right shoulder were observed. Dullness and diminished breath sounds were heard over the lower third of the right lung; the heart was normal, and there were no mur murs.- The liver edge was felt 2 fingerbreadths below the right costal margin. ^**4, , , AM MMAf* , % A 1W. OiiW* the respirations 22. The blood pressure was 120 sys tolic, 70 diastolic. , The urine was normal except for a rare red cell and 1 or 2 white cells per high-power field in the sediment. The hematocrit was 33 per cent, and the white-cell count was. 11.350. The fasting glucose was 100 mg., the urea nitrogen 13 mg., the calcium 9.0 me., the phosphorus 3.0 mg., the bilirubin 0-5 mg., and the protein 6.8 gm. (the albumin 4.4 gm., i . -269 ` No.* 14 * CASE`RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL 749 rovidc several interesting findings. First of all, a fairiy extensive reaction along the periphery right lung (Fig. 1). Its outline is irregular, i it seems to be a soft-tissue reaction extending mod the entire lung. This change means a de- asc in volume`of the lung, which is further indi- cd by elevation of the right leaf of the diaphragm d bv* retraction of the heart arid mediastinum to- id the right side. Within* the lung field there is a item of fine fibrosis and perhaps a nodular innl- te. I am less certain about, the findings on the left s, but there appears to be pleural thickening along . left lateral chest wall, as well as a similar but :ch ls marked pattern of .fibrosis and. nodular ii trace. The abnormality is-confined almost fin ely to the* perihilar and basal regions of the lungs. *.e lateral film of the chest taken at the same time ain demonstrates the elevation of the diaphragm d the extensive alteration that is apparently a ;urai reaction. A fluoroscopic spot Him (Fig. 3) <en shortly thereafter reveals a fine, linear, reticular :;sm that is probably indicative of fibrosis, and xed in with that change or superimposed upon it . see a pattern composed of very small nodules, rich in some areas, particularly in the lower tones, ce into conglomerate shadows. Finally, a high ly don film (Fig. 2), which was taken primarily hi-, it um c v* .jparc~ p.aura. renetzen, ;o demonstrates very nicely that in at least two *, the right fourth and the right fifth, the an- rior part of the cortex is missing. This picture is rtainly consistent with erosion or destruction, and ere is probably also slight erosion of the sixth and venth ribs. . Dr. Knowles: The films demonstrate that this an had bilateral pleural involvement, but pre- jjninantly of the right side. Furthermore, he had lateral parenchymal changes that were largely con- jed to the lower lobes. He also had erosive dissolu- an of at least two ribs on the right side. I'd like to k a few questions pertaining to the radiologic udies because the crux of the problem, as I see it, whether the patient had either bronchogenic car- noma or a pleural mesothelioma as a complication ' what I believe was diffuse pulmonary asoestosis. r. Dreyfuss, will you tell me about the character ' rise carina, in view of the fact that there might ive been metastatic malignant disease in the con- guous lymph nodes, which would distort it? Dr. Dreyfuss: The oudine of die carina is sharp, hat fact Is against significant subcarinai ade- j f. Hr. Kxowt.es: Secondly, would you say that the cural fibrosis on the right side definitely extends to the mediastinal structures and even Into the inracic inlet on :hat ride? Dr. Dkkykusa:..T1ic change tliac appears to be iiMiral fibrosis or thickening definitely, and probably ernfirantlv. extends alone the medial surface o( the the right lung along the cardiac and mediastinal border. Dr. Knowles: Do you see any evidence of a Fan- coast tumor, or so-called superior-sulcus tumor, in vading the soft tissues of the right thoracic inlet and thereby giving rise to the Homer syndrome? ___Dr. Dreyfuss: Of course, a soft-tissue lesion above the apex of the lung always raises the suspicion of a superior-sulcus. tumor, but I interpret the altera tion in this case as a continuous process actually encasing the lung. Another clue that I should like to see before making a diagnosis of a Pancoast tu mor is evidence of erosion or destruction of the first, second or third rib, which is not indicated on these films. Dr. Knowles: Can you state fairly definitely that fluid was absent and that the major portion of the change was due to fibrotic disease? . Dr. Dreyfuss: I am quite certain of the absence of a significant amount of fluid. The left leaf of the diaphragm is very sharp, and the usual tapered sign of fluid extending up the posterior gutter is lacking on the right side. , Dr. Knowles: One other point is that. even, though the" right hemidiaphragm was elevated the liver extended 2 fingerbreadths below the right costal margin. So I assume that there was significant K * *****Mn Iv ' * . ^ '" * Dr. Dreyfuss : It is certainly suggested. . Dr. Knowles: .As I see it, the argument in this case rests on four key findings: the disease was bilat eral and both pleural'ana parenchymal; the patient had persistent chest pain; erosive dissolution of the ribs had occurred; and a right-sided Homer syn drome had .developed. The last three features sug gest a malignant process and remove the disease from the simple class of just a fibrotic reaction to as- bestosis. The only conclusion that' I can reach is that he had chronic pulmonary asbestosis, and that a complication oFsome type had developed. At this point perhaps a brief historical review of asbestosis is in order.1 .\sbcstos is a Greek word meaning unquenchable or unconsumable in the sense of being indestructible. In 450 B. C. the Ro mans discovered that clothing made of this flexible fiber facilitated the collection of the asher, after cre mation. Its contemporary use is as insulating ma terial for pipes, linings for chemical containers and brakes on automobiles, insulating slabs and shingles, firefighter suits, theater curtains and tindercoating for ships and automobiles.1* Two years ago pul monary asbestosis was reported in Massachusetts in a man whose occupation included spraying under coating on cars5: the material used had an aphalt base with about 50 per cent asbestos, and he had true jjulmonarv Asbestos is the name given to a series of minerals composed of certain fibrous silicates, magnesium and iron. It is mined as crushed rock and is then carded, woven and spun VoL- 269 No. 14 CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL 751 Dr. Casti.f.ma*: The sputum was examined choice on the negative evidence -- that is, the nega both tumor cells and asbestos fibers, and neither tive bronchnsroptc study, the nonspecific radiologic found. findings with no suggestion of a localized mass and a.. Knowuss: My argument is becoming less the negative sputum examinations. I think that the reusable by the moment. Were the so-called asbestos operation was another right-sided thoracotomy, with, corns observed on physical examination? These arc I hope, pleural and pulmonary biopsies and per small, nodular fibrous areas that may develop on haps even biopsy of a diseased rib. I doubt whether uhe hands, arms and legs of people "wHdTvorX-with' 'curative surgery could be done. * * asbestos fibers. Dr. Lamar Souther: Why-do you think the pa Ea. :Ca-stlrman None were found. * tient lost so much weight? 'Dr. Knowuss: I should like to say a word about Dr. K.vowtss: I attribute the weight loss to the :he pathologic physiology of this disease, although debilitating effects of chronic pain and ultimate in-, it requires extraordinary courage to stick with ro/ vasion of the liver, either by metastatic disease or by original premise after ail these questions have been direct extension. Loss of appetite may be the key answered in the negative. -Pulmonary asbestosis is symptom of hepatic involvement. commonly associated with the alveolar-capillary-block Dr. Kzxxsth T. Biro: Diffuse lung disease, svndrome.* The full-blown syndrome is characterized whether or not of occupational origin, may result by reduction in lung volume, unobstructed air fiow, in weight loss. This effect is probably a manifestation increased respiratory rate and ordinarily cyanosis on of persistent hypoxia. For example, the presenting exercise, but with a normal carbon dioxide level or complaint of the patient with pulmonary emphysema* :ven mild respiratory alkalosis since there is no is often progressive weight loss. - obstruction to the diffusion of carbon dioxide. It is important to note that the crystalline form What else should be considered in the .differential and size of inhaled particles may determine the re diagnosis? Tuberculosis and fungous disease such as sponse of the host in pulmonary disease associated .ctinomvccsis are possibilities, since both cause pleu- with occupational exposure. CroridoHte, one of the -1 fibrosis and bilateral chronic disease, but there several varieties of asbestos fibers, may give rise not no* evidence of chronic infection in this patient. only to parenchymal and pleural disease but also * uis disease, with the exception of actinomy- to peritoneal manifestations.4 Chrysotile, 3MzO * ****, net erode ribc but a uciluatcai 23iO- is me mam asbestos of commercial use. jroiiferative reaction. So I can dismiss those two Dr. Castuzmax: Dr. Isselbacher, do you have a diagnoses. comment? The presence of the Homer syndrome bothered Dr. Kurt J. Isssibachsr: As Dr. Knowles men te considerably, but there is no question that a neo- tioned, in 1953 we became interested in a possible iastic mesothelioma, by Invading the lower cervical relation between asbestosis and the development of angfions and sympathetic fibers or the upper thorac- bronchogenic carcinoma. It seemed important to ; fibers, could be responsible for this condition. The document such a relation, if it existed, because of ict that it was noticed soon after the .operation the magnitude cf the asbestos industry in this coun '.ade me worry about metastatic disease or even a try. We were impressed by the preponderance of in ctle infarct in the medulla, but with no other volvement of the lower lung when the carcinoma :.sociated neurologic findings of the so-called lateral occurred in association with asbestosis. Another fac .edullary or Wallenberg syndrome one has to place tor pointing toward an association of the two en ;e cause of the Homer syndrome peripheral to tities was the high incidence of bronchogenic card- :e spinal cord and to the medulla. A superior- noma -- namely, 13.3 per cent. A third feature, :lcus rumor with invasion of the sympathetic stel- which Dr. Knowles has emphasized in this case, ;^as te ganglion or compression of the stellate ganglion the bilateral nature of the disease. In view of 'tne a cervical rib, perhaps due to manipulation dur- occupational history in the present case, I find Dr. g the operation, seems unlikely on both clinical Knowles's diagnosis most attractive. id radiologic grounds. A final point to be explained the elevated alkaline phosphatase level.' It is pos- ' Cuxtcal Dlacnoses ` aie that the high value reflected metastases to the ? Asbestosis. . or the fiver from a bronchogenic carcinoma, ? Carcinoma of lung, mterpret the elevation of the right leaf of the .* .gm as a sign of significant hepatic cnlarge- Dr. John H. Kxowi.es's Dtaoxoses em and choose to say that a pleural mesothelioma Pulmonary asbestosis. varied die diaphragm and also die liver. Pleural mesothelioma, with' invasion of medias My conclusion is that this man suffered from pul- tinum, chest wall, right. homtritnphrngm and onary ..-Mi diffuse parenchymal inter- liver. tial and nodular filnosis as well as extensive pleural >rrwis. In addition, I believe that he had a pleural Patuolocuoai. Dj<crssiox v 01. -'tUS .'"'O. I t CA.'iC i<. t^wJ v/f ijji, id or..\c.A.\i< uw^i'i lAl. . "The -patient died ten days after this operation. At axitopiy the entire right side of die chest was ob- crated by dense fibrous tissue that in many places s obviously neoplastic. In the region of die right cr lobe the pleura had a thickness of as much as 5 cm. As Dr. Knowles surmised, the pleural tumor had extended, through the diaphragm and overlay the surface of the liver (Fig. 6\. However, the paren chyma of the liver was spared cxccprfora'fcwsmalhmetastatic nodules. The neoplastic tissue extended into the lower lobe of the right lung, producing the serrated or cobblestone margin, as it projected from die pleura Into the lung, that is characteristic of the mesothelioma. The left lung was also involved by this dense pleural tumor, and there were a few small metastatic nodules within its parenchyma The tremendous mass of the mesothelioma in volved the entire mediastinum, and compression of the subclavian veins on the right side accounted for the Homer syndrome. The tumor extended down to involve the pericardium as well, and there were two small nodules on the epicardium, From the pleura it extended into the ribs, as was seen on the x-ray films, and two of the ribs were completely destroyed. The vertebras were also involved, not by direct extension but by actual metastasis. .As I mendoned, the huge tumor extended down from the chest i overlay the right lobe of the liver, and when it peeled off nodules were seen on the surface of liver. The omentum was completely covered with mesothelioma Implants, which were present throughout the abdomen, especially in the region of the right lower quadrant over the cecum, the ascend ing colon and the terminal ileum. Microscopical examination of one of the metastases within the left lung (Fig. 7) revealed mesothclial cells with a tremendous fibrous-tissue counterpart, which is characteristic of the mesothelioma, as I indicated (Fig. 8). In fact, an occasional mesotheli oma is almost- entirely fibrous, and at times it is very difficult for the pathologist to differentiate it from merely dense collagen or a fibrosarcoma- We know from experimental evidence that the mesothelioma cell, when grown on tissue culture, may produce col lagen, and that Is what it was doing in this metas tasis. On the other hand, other mesotheliomas are predominantly made up of large mcsotheiial cells. TiGUftt 7. Metastatic Nodule in the Left Lung. (X1S) r [ l \ rn;i xc 6. Sagt/tui Section through the Lotver Loire of the Right Lung, Diufihrugtn and Liver, he "esnikslU >na encircle* (he lung (above) anti *overf:et ' e -nsiteriuf surface of the liter (below). Note the pleural C.' .f, 1 \ -1 .9 ?*' .*>/ I'n.i *. !!. .!/ 'f'rt :h r t.lt r,;nee <d