Document zd2K0Nr3r4K1keq08Z98x622z

___ _ mim& - r'V^r>t'>*v^?5S:"r which padenes received muscle adenosia phosphoric acid (M.A.P.) intramuscularly and in 4 cases in which patients received adenosin intramuscularly. Evidence is presented to show that these effects are not the result of vasodilatation but are the result of some direct action on the contracting ischemic muscles. ' BIBLIOGRAPHY. 1. Barker. X. TV.; J. Am. Med. Assn., 97. $41, 1931. 2. Barker. X. W,, Brown. G. E., aad Roch. G. M.: Trace. Am. Therap. Soc., 33. 115. 1933. 3. Elliot, A> H., and Xuram. F. R.: J. PharraacoL and Exp. Therap., 43, 463. 1931. 4. Fray, E. K.: Manciea. med. Wchcacor., 2. 1951, 1929. 5. Frey, E. Berlin Letter, J. Am. Med. Asa., 95. 676, 1930. 6. Frey, E- K.. and Kraut, H.: Ztichr. f. physiol. Chem., 157, 32, 1926.----- 7. Gley. P., and Klitainioe, X.: Presse 2, 1279, 1929. * S. Roth, G- M,, Barker, S'. W,, and Brown, G. E.: Proc. Staff Meet., The Mayo Clinic, 8, 481, 1933. 9. Schwsrxmann, J. 5.: Munches, med. Wchoeehr., 2, 1329. 1929. 10. Schwarzmann, M. S.: Ibid.. 1. 758, 1930. 11. Wolff*, J. B.: Trans. Am. Therap. Soc.. 31. 31. 1931. 12. Wolffe, J. B.. Findlay. D., and Dessea, E.: Aca. Int. Med., 5. 625. 1931. A STUDY OF THE SPUTUM IN PULMONARY ASBESTOSIS. By Robert C. Page, B.A., B.M., bssidext psrstetax, rutssmBLur hospital, Philadelphia, pa.; bece>t research ASSISTANT TO PBOP. L J. STCWAST. LEEDS, ENGLAND. PHILADELPHIA, PA. (From the Department of Pathology and Bacteriology, the University of Leeds.) So much has been written on pulmonary asbestosis during the few years which have elapsed since its first recognition (Cooke, 1924, 1927; Stuart McDonald, 1927; Merewether, 1930; Lynch and Smith, 1930; Kruger et al., 1931; Ellman, 1933) that only a brief introductory statement is necessary here. The disease is a slowly progressive fibrosis of the lungs due to the inhalation of asbestos dust. The fibrosis is widespread, mainly basal and subpleural in distribution, and leads ultimately to such extensive destruction of the parenchyma that the most serious functional disability results. Death is usually brought about by some inter current infection, tuberculosis, influenza, or some form of pneu monia. The length of exposure to dust has varied within wide limits, but it is clear that gross disease may follow even as short an exposure as IS months, provided the dust concentration has been sufficiently high. A certain interval of time must elapse before the disease seriously manifests itself, possibly a period of 7 years (Merewether, 1933-19:34). At a certain stage of its development the disease can be diagnosed with great assurance on clinical and radiological examinati- to asheso stages of that a les; The As* was out by n by Gloyn deposicio: silica gel. fluids. considers a spindk " swelling with the size "to h of asbest the bod> range in from pa mainly < correspo The b occur six or emb They wpunctur finally t the spu Haddov the lun vanced ' They s> tion of finding been e>: Perse on Prc gation on a fe eight i specim Of t was cc pulcio the pr lowed 5 adenosin phosphoric acid (M.A.P.) in which patients received adenosin v that these effects are not the result resuit of some direct action on the :ograpsv. jia., 37. $41, 1931. .ad Roth, G. M.: Trans. Ad. Tberap. Soc., .: J. Pharmacol, and Exp. Therap., 43. 483, "chnschr., 2, 1951. 1929. im. Med. Assn., 95. 873, 1930. :schr. f. physiol. Chem., 157, 32, 1928. 'rejft'mii, X 1279. 1929. iQd Brown, G. E.: Proc. Staff Meet.. Tbs . aied. Wchoachr., 2, 1329, 1929. 73S. 1930. ` ap. Soc, 31. 31, 1931. Dessen, E.: Ann. Int. Med, 5. 825. 1931. t IN PULMONARY ASBESTOSIS. . Page, B.A., B.M., 3?rTAL, PSILADEtPHtA, BA.; BECENT 8E3BABCH hr. STEWAST, LEEDS, EN'GLA-VO, "ELPSIA, PA. sad Bacteriology, the University of Leeds.) in pulmonary asbestosis during the since its first recognition (Cooke, i, 1927; Merewether, 1930; Lynch 1931; Ellman, 1933) that only a i necessary here. The disease is a :he lungs due to the inhalation of widespread, mainly basal and subiads ultimately to such extensive i that the most serious functional tally brought about by some inter influenza, or some form of pneu:o dust has varied within wide limits, nay follow even as short an exposure . concentration has been sufficiently ne must elapse before the disease : y a period of 7 years (Merewether, ;e of its development the disease urap.ce on clinical and radiological ifc * i * \ X i % 5* 5u I i I T* l examination, the more so as a clear industrial history of exposure to asbestos dust is ahnosc invariably available. In the earlier stages of disordered function it may be possible oniy to suspect that a lesion is developing. ' The Asbestos Body. This has attracted much attention since it was first adequately described and its probable significance pointed out by Stuart McDonald (1927). A detailed description is given by Gloyne (1932). The bodies are formed in the lung aveoli by the deposition around individual asbestos fibers of an Iron-containing silica gel, derived partly from the fiber, partly from the surrounding fluids. They are highly characteristic in form, while presenting considerable individual variation. The two chief varieties are: (l) a spindle-shaped elongated form, very slender in the center and swelling gradually to bulbous extremities, and (2) a beaded form, with the smallest elements in the center and a gradual increase in size'to large terminal knobs. In the latter form, the central core of asbestos fiber can often be made out very clearly, especially if the body has been fractured, as often happens. The bodies, which range in size from a few up to several hundred microns, vary in color from pale green through golden yellow to deep brown, depending mainly on their size. They give the Prussian blue reaction with corresponding grades of intensity. The bodies were first observed ia sections of the lung, where they occur singly, in small groups and in radiating clumps in the alveoli, or embedded.in the fibrous tissue of the grossly diseased areas. They were next recovered from lung juice obtained by exploratory puncture of the chest during life (Stewart and Haddow, 1929) and finally these observers were able to demonstrate their presence in the sputum of asbestos workers. Later Stewart, Tattersall and Haddow (1932) recovered clumps of bodies similar to those seen in the lung alveoli postmortem from 2 cases of asbestosis, one ad vanced and since dead of the disease, the other moderately advanced. They suggested that the presence of such clumps meant disintegra tion of lung tissue and was of much greater significance than the finding of individual bodies, which merely indicated that there had been exposure to asbestos dust. Personal Observations. The following observations are based partly on Professor Stewart's collected material, partly on a reinvesti gation of the cases which he had previously examined, and partly on a few new cases first seen during* the first half of 1934. Thirtyeight individual cases have been studied, and a large number of specimens of sputum examined. Of these cases 11 have died and in 10 the presence of asbestosis was confirmed postmortem. In 6 cases there was superimposed pulmonary tuberculosis, in 2 a terminal acute bronchitis and in A the proximate cause of death was influenza. In 1 case death fol lowed pregnancy and parturition and in 1 (Case 14) an abdominal -msk In this case no autopsy was obtained. Of the surviving with pulmonary tuberculosis., 2 doubtfully tuberculous, while 9 are apparently uncomplicated cases of pulmonary asbestosis of considerable and progressive severity. Four others present evidence of mild asbestosis. Adequate informa tion is lacking in regard to 7 of the remaining 10 cases, while the other 3 are in excellent health. Of these, 2 are office employees and the third was employed in an asbestos factory only after the introduction of modern methods. In consequence she was exposed to a minimum amount of dust. Detailed examination of these cases has been going on at varying intervals for a period of 5 years. Several have been receiving medical attention for indefinite periods and the sputum has been examined at intervals when conditions permitted. Patients with pulmonary asbestosis are extremely susceptible to chest colds and coughs, particularly so during the damp winter months. It is upon such occasions that the ever-present cough becomes productive and that sputum may be obtained for examination. 1 The best time to obtain a specimen is in the morning owing to the accumulation of mucus overnight. The type of sputum varies: usually in an uncomplicated case it is very thick and tenacious and when allowed to stand develops a very disagreeable odor. When tuberculosis is associated, pus and streaks of blood are not infre quently present. The consistency in many cases is not uniform; clear, thin, watery mucus, when present', tends to settle out from the underlying thick and stringlike portion. In conjunction with this work complete clinical and radiologic examinations have been done wherever possible. In the developed disease dyspnea and cough are the ever-present and progressive symptoms. Physical signs are for the most part localized to the region of the lower chest. Roentgen ray examinations invariably confirm the findings on physical examination, and when taken at infrequent intervals illustrate a definite bilateral progressive, mainly basal, fibrosis, with characteristic signs of old pleurisy, hazy dia phragmatic margins, and so on. Complications in the nature of upper respiratory infectious, bronchitis, bronchiectasis, empyema, pneumonia and especially tuberculosis, aggravate the symptoms to a notable degree, with greatly increased debilitation of the patient and evidence of right heart failure. In all cases the sputum has been examined for the presence of asbestos bodies (including clumps) and tubercle bacilli, and in a smalt group of 6 cases a special search for elastic tissue has been made. Technique for Demonstration of Asbestos Bodies. The method orig inally suggested by Stewart and Hacldow (Stewart. 1929) consisted in adding to selected portions of the sputum an equal quantity of antiformin. Follow ing gentle agitation in a test tube and the addition of 4 or 5 times the volume of water, the mixture is placed in the incubator at 37s C. for some hours. 1. PCLirON'ARY .^BESTOSIS opsy was obtained. Of the surviving wicii pulmonary tuberculosis, 2 are ) are apparently uncomplicated cases jr.siderable and progressive severity. : mild asbestosis. Adequate informaot the remaining 10 cases, while the :h. Of these, 2 are office employees in an asbestos factory only after the )ds. In consequence she was exposed ?se cases has been going oa at varying years. Several have been receiving ite periods and the sputum has been conditions permitted. Patients with remely susceptible to chest colds and : the damp winter months. It is upon r-present cough becomes productive \ined for examination, specimen is in the morning owing to vemight. The type of sputum varies: :ase it is very thick and tenacious and ops a very disagreeable odor. When :s and streaks of blood are not infre>tency in many cases is not uniform; |hen present, tends to settle out from Jaglike portion. vork complete clinical and radiologic : wherever possible. In the developed are the ever-present and progressive re for the most part localized to the toentgen ray examinations invariably deal examination, and wheQ taken at a definite bilateral progressive, mainly ristic signs of old pleurisy, hazy diaon. Complications in the nature of bronchitis, bronchiectasis, empyema, berculosis, aggravate the symptoms to y increased debilitation of the patient failure. In all cases the sputum has ?e of asbestos bodies (including clumps) small group of 6 cases a special search .de. : of Asbestos Bodies. The method origLiddow (Stewart, 19-29) consisted in adding an equal quantity of antifotmin. Followand the addition of 4 or 5 times the volume .n the incubator at 37 C. for some hours. I tt t I I 9 * iaKt % 7 PAGE: 5PCTCM EC PCUJON'ARY ASBESTOSIS 47 The supernatant fluid is now poured on and the last 10 to 15 cc. centrifuged for 5 or 10 minutes. The supernatant fluid is again poured oif and the pre cipitate, by means of a very fine pipette, is placed on albuminized slides. The 51rn< are dried, flxed and washed, and mounted in Canada balsam. Simsoa and Strachae ;.L93l) suggested a direct- method. Thick films of the mucoid portion of sputum, were made and dried in a paraffin oven at 54 C. These were fixed with saturated mercuric chiorid solution and sub sequently stained with hematoxylin and eosin. These workers concluded that "it was as easy to demonstrate bodies in the direct Sim as in the actiformin method" and recommended its use as showing both the cytology of the specimens and the incraceliular development of the asbestos bodies. Gloyne (1931) describes a method in which ammonium sulphate replaces the hematoxylin. After aat-iformin digestion and centrifugation the anciformin is pipetted off and replaced by 5% ammonium sulphid. The bodies as a result are colored black. The author recommends this method because it allows the minute detail of the body to be cieariy seen, while the central core of asbestos fiber can readily be observed extending between adjacent segments of the asbestos body. T)r. Norah Schuster (Ellman, 1930-1931) uses the following simple wet method: The sputum is mixed with an equal quantity of 4% sodium hydroxid and left in the incubator until the mucus is dissolved (about 1 hour usually). Following centrifugation a wet Sira of the deposit is exam ined directly without staining. The method used in the present study (Stewart, 1934) is substantially the same as the original. Technique for Demonstration of Elastic Tissue. The sputum was pre pared for staining by the method of Gentz and Ber.net (1931). Three or 4 cc. of selected portions of sputum are placed in a centrifuge tube and 2 or 3 this volume of 3% caustic potash is added. It is then shaken ener getically until the mixture is homogeneous. Heat to the boiling point is now applied. Rapid cooling follows and the mixture is centrifuged for i to 1 minute. The supernatant fluid is poured off and the deposit placed on albuminized slides and allowed to dry. After being fixed with heat the Alms are carefully washed to remove the caustic potash. Two methods of staining have been used for the demonstration of elastic fibers, one a modification of Barth's method (Calmette, 1923), the other a variant of Rappaport and Ellison's (1928-1929) modification of Weigert's stain. In Method I, Barth's orcein stain is heated to 55 C. and the slides immersed. They are kept at this temperature for from 1 to 2 hours, and are then washed in water, differentiated in acid alcohol (2 to 3% hydro chloric acid in 95% alcohol), washed again in water, dehydrated in abso lute alcohol, claired in xylol and mounted in Canada balsam. The elastic fibers are stained a dark reddish purple. __ In Method II, the films are immersed in Weigert's stain, &s prepared by Rappaport and EUison, for a period of 20 minutes, following winch they are washed in water, differentiated in acid alcohol (2 to 3% hydrochloric acid in 95% alcohol), washed again in water, dehydrated in absolute alcohol, cleared in xylol and mounted in balsam. Elastic fibers are stained a deep blue-black. 'Hie relative merits of these two methods of staining are as follows: The stain as used in the Barth method is relatively easier to prepare, and once prepared can be used for au unlimited time, while the modified Weigert's stain, besides being far more difficult to prepare, tends to deteriorate much more quickly. On the other hand it stains elastic tissue in 20 minutes, whereas the modified Barth method takes from 1 to 2 hours. The final result is equally efficient aad each can be used as best fitted to the individual laboratory. * / 48 page: sputum d; pulmonary asbestosis Ta^lj: 1.--List or Cases. ;s' .y Z :J- <i3:! -; 1 -C9 Li _= ~ji < S-f 3-f Jii .we X *9 5 5v ! 5? - 31 5" .Sfar -Ss - Ciisieii -jagowi* it am* oi jpucua -73mic2Ci';2. .. " .2 . Spuruo. 3 * 3 sZ -- - 3' - 5 5 -- -- 1? 4 * 2 a Matties* maL'iw^ 5 Aiwa** subject ani: Eoettfsa r zvfz'J-t for ooclj tuccrricxU ana iscustosis. No Oesnii* RoentM at rnuiace umioa. 3 4 -- ---- -- ---- *M 3 3 Now. 2 rear* beer, appanat.y la cx^ut nsaiti. 3 Very mild abfMu: coccaucus -ir- jitem.; tough. j _ --. 34 3M Still 7 Eieetfent health; so cough. 2-- 33 OSes apt- 4M " 10 son 10 EiceHeat health: oo m?V oe eapL Now, 3 year* bar, toll in exeeSea: hearth. 3 wots* 3 F 10 saa 10 Cold; coach: gastritis; thought to be duo to uito* 27 SpfeSK eapL dan: definite jaundice. 3 Pulmonary aebestceis. ID 3F 9 4 10 Definite prograeiee basal fibrnatt. 9 __ ---- -- --* -- 27 Teaser aadcorder 7M 9 30 Etfy i 10 Pulmonary tuberculosis superimposed oe Mtnwi. 9* Coauaed poeaaortea 7 month* bur. T+ 3M 43 9a dept. 9 134 4 13 Bilateral ich associated Cuberculoeii. Coofarad ooetawnea y*v bar. 12 ++ stm 14 RiUwnl fbihwnr^ lih^afrrfti with ciTfFWr) superadded tuberculous infiltration oi upper too* -- withmoeh clerk of right lung. . 14 ++ + -- 10 M 43 dot* 13 Whit* 3 13 No data. i 12 ++ _ .. Died ot pulmonary asbeetoeb with superimposed. tuberculosis 3 yean later coofirmed ixwcnocm! li y J I It ? 11 3 18 31 Mattme eardbe fttiun; eoanmed pesnnorterm t 16 ++ + -- 12 F 31 malar 13 **** 1 18 PtoqeetiTS pulmonary asbeetoeb oi moderate! severity. Suaihrmte. _: 1 13 18 +++ + ++ -- 13 r 1 13 17 Bronchia*. , 17 + -- -- UM 13 33 Spinner 1 uM IS 33 Foreman mattreee 18 M T< 17 M 13 9 33 20 Spinoer 13 flttJttr * 12 3 18 Emphysema with dyspnea, coujh ted pain is i 12 ;+++ Vy 01; ctftfaotti of SwC). L*Ut Upuotomy im dose; death followed. ! 13 +++ 18 Polmonww tubercubeie and aeheecoeb. Connnaed by poeoaortea 1 year bter. W- ++ : -- -- + 1 IS Pulmonary atbeelceb complicated by tubemdaMt.. IS ++ + +* (T) Tobereuloeb phte aabeatOMt. : __ --21 Piogteetra pultwnary aebettwb with eardiae; inToiraaent. ! 20+ + -- Died t year bter following pregnancy and parturi* 19 F 33 3 malf*# 20 M 17 47 Mattreee 21 F 9 43 Matties* *v F 41 19 13 2 13 4 22 Ri^tt'ded basal pleural thickening; dyspnea,! cough: cubereb tuapeeted; tuberculosa coofirmed.: 20 +++ + + Primary pulmooary asbeetosb with superiapoeed aetiee tuberoulosu. 22 PulaMary asbeemia --2i +-+ + + ` 19 -- Progwaave pulmonary asbesmeia. : + --' 23 Cerebral softening; acute bronchitis and bronchi 1 poeuajoi* with associated asbrstwts. 23 r/uioi-nd bter. pceaaortent ; 23 Cough, dyspnea; evidence of basal fibrosu bv P^encgen nv er.vniradoQ. : 21 Death ten acute inhussaa 2 yearn beer. +-- -- EUttic tissue prtent (Cases 3,13. il). PTTLAION'JlRY .ASBESTOSIS --LtST O? C.i.323. Clinical dligccra* i* of saotaa wamiaasoa. :rMtoiocmataMrrwh:ia?aj'acast?Mta*. a* amative isegea y eridcac* of tttaftdL a<slat-r.CwOOpC*fimOOuU-O74icsfeMxM^iJIeTasChOeUaSlBth. . 3; 00 COUgh. ' 34. - h: Mcwth. lur, 4ail in excctkac health. nfftta:'-Soughd bean* to abate* jaaailitt. oas*i. ~- 3 10 . -K : - **ii* baa* oirtWJu . * : + j - *fwlori* aoperimpcaeii on aabcwaai*. unortea 7 aoetbs liar. l -H- ,-*!+ ssMtn with amociaied tuberoulodn. xffaortta l year kar. - 12 f +-f ! -J* =04*17 Miawmrio with sunettad' tabtccslooladltnsoo of upper km ; "H* "on*7 sbenttu with nperinpooed 3 yean later; coostmtd poaosottea. ocean aabeatoait. bronchia* sad rt; cooanMd poetaoRMa. is |++i- SlWiii1cmu7 eeboBtnie of momenta i 17 ! + ! - with dyspnea. oooch nn<l pain inI 12 ;+++!- ton of ErerfT}. later 190*401007 > ath followed. usmious and aebeatori*. ^Mantua \ yeat later. UI? !i+++++l: -~ jI . ti bettoai* complicated by tuberculoti*.: IS ; +4-' + :i* phi* aabestoai*. : ' + .uiaooaor asbeatod* with cardiac; 304* + .Of foOoaioc pmataey sod parturi-_ basal pleunl thickening; dyrpoea,! :!eipeeud;tuberculasi*niraed.' ocaiy wbesiwis rich tuperimpeaed. ttuaSiotOti*d.lL 20 a 19 +++: + <-i-H-' +.1. :- iaixuty wbotons. . - ++,+! 3:;iSofa.ssscouctiaetebdrOaDsscebaicwbsUso. d broncho- f. ' :i 3 -r , + ! .ts; evtdssce at basal fibrosis by jxaaiaaaon. u ia^unsa 7 yean later. 21 - -` page: spctum i>` pclmoxary asbestosis Tabls I.--List or Casss--Continued. 49 Ciiaicoi cia^ou at time jpurusi iiaaiisasaa. 49. Macaw Moi puloooary corceis. P?opt8v pdaoaary asotftosu. o --' -- -- 24 ; F 4 ; 37 Spinner Mi F i 16 , 44 1 Mateet* l ; ?- 13 ! | 399 Matties* 1 u! f ' ta2a1iat II 10 2 24 . Ftusksuir aebestoM :th cubereuioK*. . : Aeoeetou* vicb eseneiv* pbtbisi* confirmed by . t pemwetem 1 year Ucer. : St^eedoa of pleural edusion. < : a* . ^^ . Ftopeanve pnJmonar7 Mbesusi*. , 23 : Two yean later, adruced ssbestoet*. dry couch. ; Pulmonary aebeRoda. ; I 21 1 | ; 1 Caeoopileatedpuiaonaryasbestostiof ptooounved; : severity. j wt; ftcgeanre putnonxy asbetwn. , 27 1 : 44 ' Mattress I maker 3; if 30 ; Stiff ; I 63 Cooler | eopL 1, '! 29 i M I U | Still 30 33 Cneompiieated puitoonaty asoettofo. ! 232 : Fery serer* dyspnea; miid pulmonary aster* tori*. : Pulmonary *benois sod tubexodosi* confirmed! ; { > later Mtnonea. ! +4- ' - :++ Ceneral coodioon fairly good. i 33 ; -H- ! - 1 - I S3 ;17*rejouM empL: 1 30; P mss I ` 31 I 4 ! 33 : FairiradtaseedSbroMtfSoenbfennyexaiwsacioa^ ++ _ i _ : 671 Mattie* ! ' ! Ptogearira tmcompEeated pulaoaary aabrntoria.; -f--r 1 maker > 1 j Adranced yrtoonary fibrari*. 31: Ml 33 f .. f 30 ; 43 : Fib*rop*| | 30 >++> - / ! !i ! ; ** ! iI t Long juice. 1 Elastic dasue not present on repeated etaininauoti* (Case* 26.37.30). Analysis of Cases. The present study includes 3$ cases of asbestos workers of whom`31, where full details are available, are recorded in the preceding table. The cases have been arranged in accordance with the period of time that has passed since they first became exposed to asbestos dust, which in several cases is not equivalent to the actual duration of exposure plus the interval since leaving em ployment, since some were employed irregularly or were absent from work on account of childbirth, service overseas, etc. Twenty-one of the cases are males and 17 females. The age at which they began working in an asbestos factory ranges from 13 to 39, average 21, but 17 of the 31 recorded in the table began work before the age of 21. The average duration of exposure is 15* years, with a range from as low as 1 up to 50 years. Tuberculosis was present in S cases, and in this group the average period of exposure was 9.2 years, as contrasted with 16 years in the non-tuberculous grouD. Case 2$ is exceptional in that he was not really a worker In asbestos and he is therefore not included in the averages gtvea. Sputum Examination. Asbestos bodies hare been present in ev ery case with the exception of Case 1, a woman, aged 25, who was in contact with a minimum amount of dust as a mattress maker for ..v.<>, - -*<#r*Bifc,Vif*T *? timr PCTJIOXART ASBESTOSIS i years, the whole period being subsequent to the'abolition of the dry method of manufacture. She has always been subject to respir atory tract catarrh, which may have been a factor in preventing encry of dust to the lung alveoli. With two exceptions (Cases 1 and o) bodies were demonstrated at every examination. In Case 5 the sputum was negative after o years' exposure but positive (a solitary body only) when examined after 10 years' exposure. The number and tj-pe of bcxiies were most variable. Generally the large beaded or "weathered" type of bodies, deep brown hi color and strongly iron-reacting, were most prevalent in cases where the interval since the onset of exposure had been long, including those where a long interval had elapsed since they were last em ployed in asbestos. Bodies recovered from those who had onlybeen in this employment for a few years were smaller in size, paler in color and less strongly iron-reacting. It is clear that asbestos bodies in the lung slowly increase in size with the passage of time and become in consequence both darker in color and more strongly iron-reacting. Clumps or groups of bodies were present in 10 of the cases. Five of these had tuberculosis, of whom 3 have died and the other 2 are critically ill. One of the remaining 5 cases is doubtfully tuber culous, 1 has died of pulmonary asbestosis with associated cardiac failure, while the remaining 3 are apparently cases of progressive uncomplicated asbestosis. In 6 cases (Nos. o, 16,20,26,27 and 30) the sputum was examined for elastic tissue by the methods described and a positive result obtained in 3. In Case 5 a solitary "weather-beaten" asbestos body was discovered after 10 years* exposure, yet elastic tissue was present (Fig. 1). In Cases 26 and . 30, bodies had been found on several former occasions but neither clumps nor tubercle bacilli; elastic tissue was absent from both. In Cases 20 and 27 clumps as well as single bodies had been found previously but no tubercle Lsosmm fob Figs. I to 7. Fig. t.--Caw 5. F, age 25. Elastic tissue ia sputum of asbestos worker. Tea years' exposure to asbestos dust. Only one " weather-beaten'- body found, no clumps, no tubercle x 300. Fto. 2.--Caw 20, M., age 47. Elastic tissue in sputum oi asbestos worker. Twenty-two years since onset of exposure (duration 17 years). Asbestos bodies and clumps prewnt, but no tubercle bacilli. X 300. ' Fig. 3.--Caw 16. M., age 43. Elastic tissue in case of asbestosis with tuber culosis. Eighteen years since onset of exposure (duration 6 years), Elastic fibers, asbestos bodies and clumps (Fig. 7) and tubercle bacilli all present. X 300. Fig. 4.--Elastic tissue in sputum of a pure caw of pulmonary tuberculosis. X 30Q. Figs, 5 and 6.--Case 2$. M.. age 63. Elastic tissue in caseous material in a phthisi cal cavity. Case of pulmdnary tuberculosis superimposed upon asbestosis. Interval since onset oi exposure 30 years. X 300. Fig. 7.--Cose 16. Small clump oi asbestos bodies in sputum, from same case as Fig. 3. X 300. -,g subsequent to the abolition of the She has always been subject to respiray have been a factor in preventing .soli. With two exceptions (Cases 1 .ted at every examination. In Case 5 er 5 years' exposure but positive (a \iaed after 10 years' exposure, cdies were most variable. Generally red" type of bodies, deep brown in .g, were most prevalent in cases where >f exposure had been long, including lad elapsed since they were last emrecovered from those who had only i few years were smaller in size, paler n-reacting. It is clear that asbestos ease in size with the passage of time >th darker in color and more strongly vere present in 10 of the cases. Five vhom 3 have died and the other 2 are naining 5 cases is doubtfully tubertry asbestosis with associated cardiac > are apparently cases of progressive ^27 and 30) the sputum was examined nods described and a positive result i solitary "weather-beaten" asbestos years' exposure, yet elastic tissue was 6 and 30, bodies had been found on nejther clumps nor tubercle bacilli; both. In Cases 20 and 27 clumps as n found previously but no tubercle R % f-: i for Figs. 1 to 7. tic tissue in sputum of asbestos worker. Tea one "Veather-beatea" body found, no clumps, dastic tissue in sputum of asbestos worker, sure (duration 17 yean). Asbestos bodies and !i. X 300. astic tissue in case of asbestosis with tuber* : exposure (duration 6 years). Elsetic fibers, id tubercle bacilli ail present. X 300. i pu.'e case cf pulmonary tuberculosis. X 300. Elastic tissue in caseous material in a phthisi- i!osis superimposed upon asbestosis. Interval JCO. asbestos bodies in sputum, from same esae as \* t `.I i .? Ft3. I TO 7. 52 pace: 5PUTOI EN' PCLMOXAP.T ASBESTOSES bacilli; elastic tissue was demonstrated in Case 20 (Fie. 2). In. Case 16, clumps, tubercle bacilli and elastic tissue were ail present (Figs. 3 and 7). These results are summarized in Table 2. Xo. 5. 16 . 20 . 2o T.K3LZ >.--Cas4 Ex.litE.-BD TOR Eu_\T!C TL Aicwos b*xii**. . . . - a) ... . . . 4. Clasps. -- -f-- Eiaacic tissue. + - -r -- rur,-ircl Discussion. The findings here reported are for the most part in accordance with those of other workers and show that the mere presence of asbestos bodies in the sputum of an individual denotes nothing more than that he has at some time been in contact with asbestos dust.. The actual- number of bodies is likewise of little significance. If, however, they are consistently present in consider able numbers the possibilities are that either the individual has been in coatact with large quantities of dust over a long period or there is some underlying pathologic condition of the lung, leading to gradual liberation of accumulated bodies. This is illustrated in Cases 14 and 19. In the former the sputum upon repeated examina tion showed large numbers of bodies, the individual in question having been associated at the time of examination and for 15 years previously with large quantities of dust. Case 19, on the other hand, also with numerous bodies on repeated examination, had only been directly exposed for a period of 6 years and had not been in contact with dust for 16 years at the time of examination. Clinic ally there was an associated tuberculosis. The type of body present is of considerably greater significance than the number. The formation of asbestos bodies in the lung takes but a short time. They were found by Simson (1929) in the lungs of a patient who had been exposed for 2 months only, and by Stewart (1930) in a guinea pig after 3 months' exposure in an asbes tos factory. Once formed, they can remain in the lung for an indefin ite period. In a patient of EUman's (1933) exposure was for 10 weeks only, and 5 years later bodies were recovered from the sputum. In Case 13 of this series, the patient had worked in asbestos for 1 year, and 17 years later bodies were still present in small numbers. Reference has already been made to the "growth" or increase in size of these bodies, presumably by slow diffusion out of silicates from the central fiber and their interaction with constituents of the surrounding body fluids. It follows that bodies of large size in the sputum indicate that these have formed around fibers inhaled many years before. On the other hand, small, thin bodies, though doubtless of recent formation, are no indication that their central fibers have been recently inhaled. "Young" bodies may be en countered in sputum from persons who have had no opportunity .TMON'ART ASBESTOSIS .strated m Case 20 (Fig. 2). In and elastic tissue were all present summarized in Table 2. :n-e for Elastic Tissce. T'.uiap*. Elastic tissue. Tubcre!# bacilli. + " ." reported are for the most part in workers and show that the mere e sputum of an individual denotes t some time been in contact with ber of bodies is likewise of little e consistently- present in consider- re that either the individual has ities of dust over a long period or >gic condition of the lung, leading iced bodies. This is illustrated in be sputum upon repeated examina- ^odies, the individual in question pe of examination and for 15 years of dust. Case 19, on the other ?s on repeated examination, bad period of 6 years and had not been .c the time of examination. Clinic- culosis. ` t considerably greater significance >q of asbestos bodies in the lung -re found by Simson (1929) in the xposed for 2 months only, and by er 3 months' exposure in an asbes- a remain in the lung for an indefin- '.an's (1933) exposure was for 10 s were recovered from the sputum. ;cient had worked in asbestos for ere still present in small numbers, i.le to the '"growth" or increase in by slow diffusion out of silicates ceraction with constituents of the ws that bodies of large size in the e formed around fibers inhaled hand, small, thin bodies, though e no indication that their central I. "Young" bodies may be en- \s who have had no opportunity T i t k f * i r i PACeT-SPCITM D.' PCLMOXABY ASBESTOSIS ot inhaling dust for many years, and it is known that asbestos fibers may remain in the lung for long periods withouc necessarily becoming converted into "bodies" at all. Another point of great importance is the so-cailed ``weathering" of the asbestos body. Many of the old large bodies present a dis tinctly ragged or weather-beaten aspect, often consisting, as it were, of widely separated irregularly shaped beads strung on the fibrous core. There can be little doubt that this process is associated with solution and disintegration of "body" substance and accounts, in my opinion, for the interesting finding of Fowweather that the silica content of the Sbrotic portion of the asbestos lung is much less in workers who have been away from dust for many years than in those recently or still in employment, even where the length of exposure has been the same. "Weathering" is probably a constant process in these cases, but may be accelerated by the occurrence of caseous or suppurative change. The clump-like arrangement of bodies within the lung alveoli was observed from the very outset of detailed histologic studies (Stuart McDonald, 1927). When the presence of clumps in the sputum was first reported by Stewart, Tattersall and Haddow (1932) it was suggested that this finding was a clear indication of disintegration of lung tissue, whether by a process of simple sup purative bronchopneumonia or as a result of a secondary tuber culous infection. In either case it was regarded as being virtually diagnostic of an underlying asbestosis. In the present study, 10 cases in which clumps were present in the sputum tend to substan tiate this view. Four of them suffered from superimposed tuber culosis!. Two of these have died and the remaining 2 are now critic ally ill. One other patient in whose sputum a clump was demon strated is considered as^a probable case of superimposed pulmonary tuberculosis. Of the remaining 5 cases, 2 have died, 1 of cerebral softening, acute bronchitis and bronchopneumonia, the other of bronchitis and cardiac failure, both with underlying asbestosis. The remaining 3 are suffering with definite progressive pulmonary asbestosis, fully confirmed by clinical and radiologic examination. While the presence of asbestos clumps in the sputum is probably indicative of lung destruction, the converse is by no means true, that is, the absence of asbestos clumps affords no assurance of pulmonary integrity. There are many cases in the present series in which there has been, definite disintegration of the lung and yet no clumps have been demonstrated in the sputum. Other possible fallacies exist. More prolonged and more careful examination might have yielded a positive result, or roughness in handling may have caused the clumps to break up. Lastly and perhaps most important, the underlying pathologic condition in the lung may have led to chemical or physical dissolution of the clumplike arrangement so that when expectorated in the midst of caseous material or pus, the clumps may have disintegrated into their individual fibers. t jm|pmjm|ig Gardner and Cummings (1931) state that in guinea pigs tuber culous caseation causes the asbestos bodies present to lose their golden-yellow* color: they also fail to give a Prussian blue reaction and later are apparently so completely disintegrated that not even a supporting fiber remains. Elastic tissue in the sputum, irrespective of the underlying patho logic condition, has long been accepted as unequivocal 'evidence of lung disintegration; Rappaport (1929-1930) mentions that elastic tissue may appear in the sputum of patients who present only very mild signs of clinical activity. He refers to Durand, a French worker, who demonstrated elastic fibers in the sputum of tubercu lous patients, both before and after the appearance of tubercle bacilli. The 3 cases of the present series in which elastic tissue has been demonstrated in the sputum illustrate several points of interest. In Case 5, the presence of the elastic fibers is difficult to explain. She had been exposed to asbestos dust, it is true, for the last 10 years, and during this time it is quite possible for a progressive pulmonary asbestosis to have developed. Vet only a solitary asbestos body was found on one occasion. There was no definite evidence of tuberculosis, but the possibility that this disease existed in an abacillary or prebacillary stage could not be excluded. In Case 20, the presence of elastic fibers is associated with a rapidly progressive form of uncomplicated pulmonary asbestosis. In Case 16, the presence of elastic tissue is associated with active tubercu losis and clearly indicates a state of definite disintegration. The underlying pulmonary lesion here is probably illustrated by Case 28, from which Figures 6 and 7 were obtained. These show, in sections of the lung, elastic tissue in the midst of caseous tuberculous mate rial, in a similar form to that expectorated in Case 16. A careful search for tubercle bacilli has been carried out in every sample of sputum obtained. Positive findings were present in 6 out of 8 cases of proven tuberculosa. The incidence of tuberculosis in this series is therefore 21%, exactly the same as that recorded by Wood and Gloyne (1931), but less than figure given by EUmaa (1930-1931), 6 out of 17 cases. Bridge (1931) reports an incidence of 31.5% in fatal cases. Conclusions. 1. The presence of asbestos bodies in the sputum is indicative merely of exposure to asbestos dust. If they are of large size it means that a long interval has elapsed since the onset of exposure. 2. The number of bodies in any given specimen is insignificant, but the presence of old and weathered bodies on repeated examina tions strongly suggests that a definite pathologic process is in exist ence. 3. Clumps in the sputum are definite evidence of lung disintegra tion, but their absence does not mean that disintegration is not in process. 4. Elastic fibers are probably indicative of rapid lung destruction. .I'.Xll) state that in guinea pigs tuberasbestos bodies present to iose their so fail to give a Prussian blue reaction completely disintegrated that not even m, irrespective of the underlying patho?rt accepted as unequivocal evidence of port (1920-1930) mentions that elastic itum ot* patients who present only very icy. He refers to Durand, a French elastic fibers in the sputum ot tubercuand after the appearance of tubercle .resect series.in which elastic tissue has itum illustrate several points of interest. the elastic fibers is difficult to explain, sbestos dust, it is true, for the last 10 * it is quite possible for a progressive ave developed. Yet only a solitary i one occasion. There was no definite : the possibility that this disease existed llary stage could not be excluded. In \stic fibers is associated with a rapidly Heated pulmonary asbestosis. In Case *ysue is associated with active tubercu0 state of definite disintegration. The 1 here is probably illustrated by Case 28, were obtained. These show, in sections the midst of caseous tuberculous matec expectorated in Case 16. cle bacilli has been carried out in every .. Positive findings were present in 6 ?rculosis. The incidence of tuberculosis %, exactly the same as that recorded i, but less than figure given by Ellman es. Bridge (1931) reports an incidence aace of asbestos bodies in the sputum sure`to asbestos dust. If they are of g interval has elapsed since the onset of ; ; * . ' : ; ' i . : ; ' i | ; ' t j j j in any given specimen is insignificant, weathered bodies on repeated examlnax definite pathologic process is in exist- > L . .ire definite evidence of lung disintegraaot mean that disintegration is not in >ly indicative of rapid lung destruction. 5. Elastic fibers may be present in the sputum in pure pulmonary asbestosis both with and without clumps, or in asbestosis with associated tuberculosis. 6. The routine examination of the sputum in cases of suspected pulmonary asbestosis is essential, as it plays a significant role in the clinical diagnosis. I wish to express iv sincere appreciation to Professor M. J. Stewart for the use of his personally collected material, his friendly criricisn and able advice. under whose guidance this paper bos been written, and to the British Medical Research Council iorIianmaaaclisaoi iansdseisbttaendceto. Dr. A. C. Haddow and Dr. N. Tattersail for the use of their clinical ana radiological material, and to Mr. Lawson for his technical assistance. REFERENCES. . Bridge, C.: Ann. Rep.. Senior Med. Inspector ot Factories, p. 74. 1031. Calmette, A.: L'infection baciilaire et la tuberculose. 3r ed.. Masson, Paris, p. 499, 192S. Cooice, W. E.; Brit. Med. J., 2, 147. 1924: Ibid.. 2, 1024. 1927. Ellman. P.: Proc. Roy. Soc. Med., 24, 523, 541. and 699, 1930-1931: J. Induet. Hygiene, 15.165. 1933. Fowweather. F. S.: Personal communication. 1934. Gardner. L. U.. Cummings. D. E.: J. Indust. Hygiene, 13, 65 and 97,1931. Cents. C.. and Bennet. K.: Acta Med. Scandinav., 75, 424. 1931. Glovne. S. R.: J. Indust. Hygiene. 13. S5, 1931: Lancet. 1, 1351, 1932. Kruger, E., Roetosld, O., and Sauce, E.: Arch. f. Gewerbepath. u. Gewerbehyg.. 2. 55S. 1931. Lynch. IC M., and Smith. TV*. A.: J. Am. Med. Aaan., 95, 659,1930. McDonald. 3.: Brit. Med. J.. 2, 1025. 1925. Merewether, E. R. .V.: J. Indust. Hygiene, 12, 19S, 1930: Tubercle, 15. 69, 109 and [52. 1933-1934. Rappaport, I.: J. Lab. and Clin. Med., 15, l, 1929-1930. Rappaport, I.. and EUisoa. R. T.: Ibid- 14, 261.1923-1929. Simeon, F. \V.: Ann. Rep. So. African Inatit, Med. Res., p. 64, 1929. Simeon, F. TV., and Strachan. A- S.: J. Path, and Bact., 34. 1, 1931. Stewart. M. J.: Brit. Med., J. 2, 581. 1929; J. Path, and Beet.. 33, 84$, 1930; J. Tech. Methods and Bull. lateraat. Assn. Med. Museums. 13, 70, 1934. Stewart, M. J., and Haddow. A. C.: J. Path, and Bact.. 32, 172. 1929. Stewart. M. J.. Tattersail. N.. and Haddow. A. C.: Ibid.. 35. 324. 1932. w * -ndfllovae. S.R.: Ibid.. 2.954.1931. ACETYL-/3-METHYLCHOLIN (MECHOUN). OBSERVATIONS CONCERNING ITS ACTION ON THE BLOOD PRESSURE, SKIN TEMPERATURE AND THE HEART, AS EXHIBITED BY THE ELECTROCARDIOGRAM OP HYPERTENSIVE PATIENTS. By Irvine H. Page, M.D., ASSOCIATE IN* MEDICINE, HOSPITAL OF TEE ROCKEFELLER INSTITUTE FOR MEDICAL RESEARCH, NEW VORil, -V. T. _ Hunt and Taveau1 were the first to prepare and determine many f the pharmacologic properties cf aeetyl-3-methyieholin. Major and Cline2 have s^mthetized it ("mechoiitr) by a process which has made it available In quantify. Recently studies of its pharmacology