Document 93Mpv6bXoYKa9x0dDV9d30gL5

FILE NAME: Exxon (EXX) DATE: 1935 DOC#: EXX001 DOCUMENT DESCRIPTION: Medical Journal Article - A Study of the Sputum in Pulmonary Asbestosis Tir e E . H. TvKUM HIAAB, I O . EDITOR JUCH A E D A. ICE RN, M.D. ASS IS'['A NT EDI'I'OR N V. W S K R I R S VOL. ISO LEA & FERIO LE l'IIir-ADI-IUMNA ,11 s i t t i .m i x i m 'i a i o x a u v \ s j u n t o s i s which patients received muscle ailcnosin phosphoric aeid (M.A.fi.) intramuscularly ami in l cases in which patients received adenosin intramuscularly. Kvidenee is presented to show that these ell'eets an: not the result of vasodilatation hut arc the result of some direct action on the contracting ischemic muscles. miu.ioc.ii.u'iiY. 1. ll.irki-r. N . W .. .1. A m . Assn., 97. M l. 2. B a rk e r , X. W., Bidw u. G. K , a n d B o th , (1. M .. T r a n s . A m . T h e r a p . S>c., 3 3 . ur>. h >33. 3. FUiof. A. U.. a n d X i i/n n t, V. R.. J. P h a n m t ro F a n d Kxp. T h e r a p . , 43, il>3, 193F 1. F re y , K. K . : M i'm ch fn . m od. W e lm s rh r ., 2, 11)31, 11)21). 5. F re y , K. K .: i i r r l i n l.t-Urr, .1. Am. Mwl. Atasn., 95. b7t>. 11>30. t>_ l-'rey, K. K., a n d K r a u t , I I . . Ztscdir. f. physiol. 157, 32, l!)2b. 7. O lcy , P., a n d K isth m iu s, X .: P re ss e mi'iL, 2, 1371), 1021). 5. R u t h . (T. M.. B a rk e r . X . W., a n d Brow n, G. K.: P ro c . S ta f f M e e t., T h e M a y o Clinic*, 8. 1M. 1033. 9. Sch sv ar/.m aim . i. S . ^ M i m t lien. im*d. WVItn.st hr., 2, 1320, 1929. 10. .Srhu'arzmaiiii, .M. S.. Ihid., 1, 75'-\ 19-30. 11. Wolffe, .J. B * 'T ra ns. A m . T h e r a p . Soi*., 31. 31, 1031. 12. WoliTe. J . B., F in d lay , 1).. a n d D e ^ u n , I v . A n n . I n t . M e d ., 5, (>2o, 1931. A STUDY OF THE SPUTUM IN PULMONARY ASBESTOSIS. RESIDENT B y B oukut P H Y S I f : l \ N , 11U > It V T K ! U . \ N A W b i ANT TO IMIOK. ('. Pack, B.A., B.M., H O fs P lT \ f,, W i l l , \ UK L P H I P.\ . i II K C K N T M. J . .VC hU M U '. I . h h l H , I . N U L A N D . UKSK.N IlCII (From the Department of Faliiology and liaiderioio^y, the Cmwr&Uy of Feeds.) So much has been written on pulmonary asbestosis during tlie few years which lmve elapsed since its first recognition (Cooke, 1921, 1927; Stuart McDonald, 1927; Mercwether, 19d(); Lyneh and Smith, lO.Jl); kniger ft ul., 1!).'!1; Klhtmn, 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 sub- pleural in distribution, and leads ultimately to such extensive destruction of the parenchyma that the most serious functional disability results. Heath 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 cross disease may follow even as short ail exposure as IS months, pro\idcd the dust concentration 1ms been sufficiently high. A certain interval of time must elapse before the disease seriously manifests itself, possibly a period of 7 years (Mercwether, 19dd-l!).'i 1). At a certain stage of its development the disease can he diagnosed with great asairanee on clinical and radiological I'A C i : : S C U T l ' M IN' I T I . W O X . U I Y Vs 111I s T O s I s 'Ni, examination, tlm more mi as a clear industrial history of exposing to asbestos tlust is almost invariably available. In the earlier ' stages of disordered function it may be possible only 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 (lloyne (19:>2). 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: (1) 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 in sections of the lung, wheic the;, 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 Iladdow, 1929) and finally these observers were able to demonstrate their presence in the sputum of asbestos workers, hater Stewart, Tattersall and Iladdow (19d2) recovered clumps of bodies similar to those seen in the lung alveoli postmortem from 2 eases of nsbestosh, one ad vanced mid 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 bad been exposure to asbestos dust. Personal Observations. The follow ing observations are based partly on Professor Stewart's collected material, partly on a reinvesti gation of the eases which he had previously examined, and partly on a few new eases first seen during the first half of IOdd. Thirtyeight individual eases have been studied, and a large number of specimens of sputum examined. Of these (uses 11 have died and in 10 the presence of asliostosis xvas confirmed postmortem. In ti eases there was superimposed pulmonary tuberculosis, in 2 a terminal acute bronchitis and in 1 the proximate cause of death was influenza In t ease death fol lowed pregnancy and parturition and in 1 (Case 11) an abdominal 46 l'ACF.: S I T T l ' M IN l'l I.MOXAUY AslM'.STOS IS operation. In this case no autopay was obtained. Of the .surviving cases, 2 are now acutely ill with pulmonary tuberculosis, 2 are doubtfully tuberculous, while 1) are apparently uncomplicated eases of pulmonary asbestosis of considerable and progressive severity, hour others resent evidence of mild asbestosis. Adequate informa tion is lacking in regard to V of the remaining 10 cases, while the other 2 are in excellent health. Of these, 2 are ofiiee 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 eases has been going on at varying intervals for a period of 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 he obtained for examination. 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 ease it is very thick and tenacious and when allowed to stand develops a very disagreeable odor. When tuberculosis is associated, us and streaks of blood are not infre quently present. The consistency in many eases 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 progress)ve, mainly basal, fibrosis, with characteristic signs of old pleurisy, hazy dia phragmatic margins, anil so on. Oomplitations in the nature of upper respiratory infections, 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 small group of 6 eases a special search for elastic tissue has been made. Technique for Demonstration of Asbestos Bodies. The method orig inally suggested by Stewart ami ltaddow (Stewart, 102!)) consisted in adding to selected portions of Iho sputum an equal quantity of antifonnin. Follow ing gentle agitation in a test tube and the addition of 4 m turn ., the volume of water, the mixture tx placed in t h e imubator at .'7 (.'. for some hours. t a c k : s i m t i ' m in* i t i a i o n a k v a m u -v t o ^ k 'The supei 11.1Iant lliiid E 111>\v pi >timl i>ITand the last. 10 to I.'><( in i 11if11u<'E for 5 or II) minute.-,. The supernatant, UnitI is again [mured oil .nrI the pre cipitate, by means of a \ery line pipette, is pl.u.-eil on albuininiyoiI Aid,-. Tile films are ilrieil, fixed ami washed, and uumnted in ( an.uda balsam. Sinisou and Stiaclian (1931) suggested a direct method. Thick lihns of the mucoid portion of sputum were made and diie.d in a paraffin oven at 54 C. These were lixed with saturated mercuric chlorid solution and sub sequently stained with hematoxylin and cosin. These workers' concluded that " it was as easy to demonstrate bodies in the direct him as in the anliformin method" and recommended its Use as showing both the cytology of the specimens and the intracellular development of the asbestos bodies. Gloyne (1931) describes a method in which ammonium sulphate icplaces the hematoxylin. After antiformin digestion and centrifugation the antiforinin is pipetted off and replaced by 5% ammonium sulphid. The bodies as a result arc colored black. The author recommends this method because it allows the minute details of the body to be clearly seen, while the central core of asbestos liber can readily be observed extending between adjacent segments of the asbestos body. Dr. Norah Schuster (Ellman, 1930-1931) uses the following simple wet method: The sputum is mixed with an equal quantity of 4% sodium hydro.xid and left hi flic incubator until the mucus is dissolved (about 1 hour usually). Following centrifugation a wet him of the deposit is exam ined directly without staining. The method used in the present study (Stewart, 1931) is substantially the same as the original. Technique for Demonstration of Elastic Tissue. The sputum was [irepared for staining by the method of Gentz and Bonnet (1931). Three or 4 cc. of selected portions of sputum are placed in u centrifuge tube and :1 or 3 times 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. Uapid cooling follows and the mixture is centrifuged for 1 to 1 minute. The supernatant fluid is poured oil and the deposit placed on albuminized slides and allowed to dry. After being lixed with heat the films 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, BUS), the other a variant of liappaport and Ellison's (BUS-TOT.)) modification of \\ cigert s stain. In Method I, Barth's orcein stain is heated to 55" G. and the Aides immersed. They are kept at this temperature for from l to 2 hours, and are then washed in water, differentiated in acid alcohol (2 to 3 r,', hydro chloric acid in 95(A alcohol), washed again in water, dehydrated in abso lute alcohol, cleared in xylol and mounted in Canada balsam. The elastic fibers are stained a dark reddish purple. In Method II, the lihns are immersed in Weigerl's slain, as prepared by Rappaport and Ellison, for a period of 21) minutes, billowing which 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 libers are stained a deep blue-black. The relative merits uf the-e two methods of staining are as follows. The stain as used in the Barth method is relatively' easier to prepare, and once prepared can lie u.-ed for an unlimited time, while the modified WeigertA stain, besides being far more ditiieult to prepare, tends to deteriorate much more quickly On the other hand it stains elastic tissue in 20 minutes, whereas the modified Bartli method takes from 1 to 2 hours. The final result is equally eiheient and each can lie used as best fitted to the indi\ iduul laboratory. r.vfii',: s i t t ' m i x l'c m n x A i i V a s h k >t o s i m .. -- . ' ' ' 4> <0 ? : 1 ! i ! ti 1 . # ' s'h 9 9 o 2 e> .2 _ .J ~ 3 S '3 * ' M i . ,- ;3 b = 9. 7* y ~3 3 * o d-- a ~ 2 a -S T i b i .c I. -- L i s r n r C w 4. ( 'Iimcnl ,it lim e <>f sputim i ex am in atio n . Spulino z3 , r "I 1 ! ^ | Clumps. 1 V 4 j 25 M attress m aking 2! M 34 3 M: 36 | 1 Ii 4' M ! i 28; 5 F. , 27 , 3 Spinner 7 Onice worker ID Office worker 10 Spinner ! 3 1 Still I empi. Still em pi. ' Still empi- 6 ! T easer ami cordar ; 7 ! M | 30 L,,ve,Jry 1 8 1 M dep)t. ! 1 45 9 : M i i3i sun 37 IA-ssoauted trnpl. with m uch, clerk dust IO, M 12 46 Wduhaitle 11 V 11 31 M a ttre s s m aker 1 15 1 12j M attress | m aker 1 13 ! F 16 ! 44 15 14 ' M I S p in u ir 13 M 36 18 F orem an HidltrtN.'t 16 M m akt>er I : "17 M ; 20 ! (?) Spurn r 18 F 15 3 35 M attresd m aker 19 K 35 20 M 47 21 F 45 22 F 4 ( 6 lt> M a ttrt"vi um ktr 17 2 Mattr>n*t m aker 1 6 J 15 M attress m aker I ; 4 M altrcsa ! maki r ti A lways M ibjeet to c a ta rrh , Ib>cnti:rn ray neitative for Unii Inf n uhi.'iiA au< { o-'ln-to-i'i. 3 N o >Iehmlc Kt*'iitL;cn ray evidence `>1 a-slxMo-ns 4 | Now. J \ea rs lat'-r, apparently in c w e lh n t health. , i - 6 I Very w ild hbriM s; (o n tim m u s dry ha knu.' cuukIi. -h 1- 7 Ijtcellcn l In alili, no coni'll. 10 Excellent h e a lth ; no couch. Novr, 5 years later, sull in excellent health. 1 i" - 2 j + 1 5 . -b - ID Cold; eounh, u a s tr u n ; ih o u u h i to Inr Ino to L'lw'-ios d u st, dilnut jaiirniii i. I'ulm onary j.-,l>eslosis. D efinite progressive ba.sal fibrosis. 10 . lA ihnonary tiil*Tciilosis nupcrim poscil on nsl*t>io`>n 1 Conlirmcd postm ortem 7 m ouths later. 5 -- ID d* 0 \+ 1 ! d-d- _ -- - ' + d- 13 ` B ilateral a.sl>e>tOsis with associate! IuIx.tcuIo.sis. Confirm ed ixM tnoricm 1 >**,\r later. u 11 l B ilateral pulm onary asl>estosis w ith suiimM*! sujhraddi J tubertulous m filtrainm of upper one of riiibt lum;. Iu ++ j + + d- d- - 15 N o data. 12 | d-d- - - D ied if p u lm onary asU-stosW w ith superm um s1 tuberculosis J years later; confirmed jxr-im orteni. A dvanced pulm onary a-lx-Miosis, hrom hitia and 1 cardiac failure; confirmed j*o.stin>rteni. j 16 ' + + d- - ProejeMsivc pulmonary aslx-Mosis of mo*l rule seventy. , 16 + + - I - d- _ Similar state. i It) d - h -- -- Bronchitis. j 17 ; + -- - : Em physem a with dyspnea, couch and pain in | alxiotnen [ 12 d -d -d - - - Very ill; cuThoais nf ti\ir ( ? ) . lo ite r laparotom y ! was done; death followed. \ Ihilm oiiary ud*.ri.ultens an*l a-lx-stods. i 13 '+ + + - _ 17 d-d* d- | Coniirim d by jxxstnmrtetu l year l a u r | P ulm onary aslx-itusn compii at-d by tul* r u I<m s . , IS d*d* d- + (?) T u U ri ulosis plus osln sio-us. (- 1 21 Progressive pnljtnm ary .vd*-*tMis w ith lard in e involvem ent. Jtid- d- ' - - Died 1 y ta r later following prvenam y mul p artu ri tion. 22 llicb l-aid i d laaaJ pleural th i` km iui; d y spnea, ' ! couch; tut>**rciti suspected; h ib c m iln o s -onfirmed. P rim ary pulm onary aaU-slosis w ith supernn|*^*d 20 + + + ; + 1 + , j a c m e lui* r< ul>*es. 2' d -d -d - + ! d- 22 Pulm onary oslx-slntas. ' l*n>Kri"*sive pulm onary asU ^tosis, i `> d -d - - ! 22 d - d - . d - i - 2.3 IC erebral soft niitii; a c u te bronchitis a n d pneum onia with a>soruiirl tialicstosis. broncho 2- 1 . i i d- : - 23 Confirm ed at r. ixeilm ortcm . ('on}), d y sp m u ; iv id i m e of h.is.it fibrosis by 21 j j d- ; - ! - Hih IiICi n ray ro m in a ti-m . D m th from j i u l e titilli im i 'J years later. Elastic tissue p n s e n t (Po-s-i r>, 16 .2 0 ). r.\(;r.: M'i-n \i i \ rn .\io\'\u v xsimsTosi.s T \ h t,i. 1 - --L i v i > r <! \ ti --f 'm l/ o u n { `S,s -- u yr. 4 - r. c 7 -- a *2 il ^4 i = 7 - -- p = = 5 ~4 r / .C ?m - 7 = -= -- ~ = -- <`Umrnl di.e.MUV'J' .il lone of 'p iitn in i-xamiiiat mn. Xi 7 x ~ C H 'a - _y t i l -ut mu -- ~ r- z b ? 3 " r.i y 40 24 V 37 25 . y 41 26 V 39 27 r 4 b 2$ M 63 >> , M atin.". m aker 4 u ppmm r If. M attr -d mak r 13 M altrri-d m aker 21 M :nrss makt r 30 COrthier *> 10 2 S o il rm pl 29 M 35 ritill .10 \Van-hoi>e empl m an 30 F .H 4 67 M a ttre ss m aker 31 M 50 63 1-itit-r rijn> J> |>t. 21 M iM p u liu o n .m hhr.Kis I*fogn-vi\r pulmonar) 2 V i'u lm o tu rv l- 1 * stu si' with tuliereul<M->. A -la-r*-n w ith e \tu s i\e phthi'i-. um hrinm l |>\ l-.su ru -rti m l ,ir l,r* r 2." Mig_*i 'tu r n if pi. tir.il t. ]*ri>gn-"j\e |Mtltiii.n,ir\ a.-'ld'-iu'-i.- T w o u a r s Lili r, :ii\ a m d a.sU-ai-!', dr) cough. 2 Pu lm o n ary a-d*-loM '. I 'm iqnplu at 0 pulm onary of pronounced 'vi r iu 29 IVogriT-.-ixr pulmim.irv a.drfMmF. 1 m um plii .if< >1 pulm onar) tU'lie-bi'is. io \'i r\ -* i e rr ro u g h . il) nuld pulm onar) :l-1>cs- fo-ls P ulm onary am i iu U tcuIo-u u m h rm e d lat< r l>inn>n-m 35 G etn ral lo n d iim n f.iirlv good. 1^ . t 24 - 25 -- 22 -T 23 2J -- 2*>t 27 T " 2`J t -- 25 + -- 31) .55 - r - r --_ _-- ---- __ _,, -- -- __ --_ --_ _-- __ 35 Kairlv al\aneed filiro'i-, (Kornliren r a \ exam ination) 26 + 4- _ _ l `rogn-sM \e u m o m p in a ltd pulm<iiar\ a-'U -to.'is. 3 i ; 4*t _ _ 50 A dvanced pu lm o n ar) fiimna.s. 5*J F-t- - t Liuil' juii-f. I i'liL>l 1L lloue ni>t prt'MTil mu ri-j.i:it':l nwtn il '.m-i Jr>. 27. .top Analysis of Cases. The present study includes 38 cases of asbestos workers of whom '1, where full details are asailabie, are recorded in the preceding table-. 'The cases have been arranged in accordance with the period of turn; 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 ploy itient, since some were employ ed irreyidarh or \\ ere absent from work on account of childbirth, service overseas, etc. Twenty-one of the cases are males ami 17 females. The aye at which they beyan working in an asbestos factory ranges from id to 39, averaye 21, but 17 of the 31 recorded in the table beyan work before the aye of 21. The average duration of exposure is lb years, with a range from as low as 1 up to '>() years. Tuberculosis was present in 3 cases, and in this group the average period of exposure unis 9.2 \ears. as contrasted with !(> years in the non tubcretdotis group. Case 28 is exceptional in that lie was not really a worker in asbestos and he is therefore not included in the averages given. Sputum Examination. .Ubrxtox bodirt have been present in every case with the c\( option ot Case 1, a woman, aged 3b, who was m contact with a minimum amount of dust as a mattress makei for 46 1> \ C K : SI M' Tl / M IX VI I.MOX.VKY . \ > m X T f v K operation. ]n this case no autopsy was obtained. Of the surviving cases, 2 are now acutely ill with pulmonary tuberculosis, 2 are doubtfully tuberculous, while 9 are apparently uneomplicated cases of pulmonary nsbestosis of considerable and progressive severity. Four others present evidence of mild nsbestosis. Adequate informa tion is lurking in regard to 7 of the remaining 10 eases, while the otlu-r :> are in excellent health. Of tbe.se, 2 arc oflicc 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 eases has been going on at varying intervals for a period of 6 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 arc extremely susceptible to chest colds and coughs, particularly so during tiro damp winter months. It is upon such occasions that the ever-present cough becomes productive and that sputum may he obtained for examination. The host time to obtain a specimen is in the morning owing to the accumulation of mucus overnight. The typo 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 arc not infre quently present. The consistency in many eases is not uniform; clear, thin, watery mucus, when present, tends to settle out from the underlying thick and stringlikc 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 infections, 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 small 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 Iiaddow (Stewart, 11)2!)) consisted in inkling to selected portions of the sputum an equal quantity of antiforinin. Follow ing gentle agitation in a test tube mid the addition of 4 or 5 tunes the volume of water, tlie mixtiiie is placed in the incubator at 27" C. for some hours. l-.VCK: s l T T C M IN' m . M O N U i V . Vs l SKs TOSl s The siipri 11:11:i111 Ili11<1G now puiired oil and IIn1la-d, ID to I5 re. irnl lilum for 5 or II) minuter, 'l'lie supernatant Ihiid is again poun'il off and IIn- pre cipitate, by means of a very line pi|>e||e, B phneil on ulbmniui/.cd .-!ii!i~. The iilms are dried, fixed anil washed, and mounted in ( `amnia bnF:un. Simson and Strachan IlDdl) suggested a direct method. Thick lihn< ul" the mucoid portion of sputum were made and dried in a paralhn oven at 54 0 . These were fixed with saturated mercuric chlorid solution and sub sequently stained with hematoxylin and rosin. These workers concluded that " it was as easy to demonstrate bodies in the direct film as in the antiformin method'' ami recommended its use as showing both the cytology of the specimens and the intracellular development of the asbestos bodies. Gloynu (11)111) describes a method in which ammonium sulphate replaces the hematoxylin.' After antiformin digestion and centrifugation the antifonnin is pipetted off and replaced by 5% ammonium sulphid. The bodies as a result arc colored black. The author recommend-; this nu-tliod became ' it allows the minute details of the body to he clearly seen, while the central core of asbestos liber can readily be observed extending between adjacent segments of the asbestos body. Dr. lXorah riehuster (Fllman, l!)30-193l) uses the following simple, wet method: The sputum is mixed with an equal quantity of 1% sodium hydro.xid and left in the incubator until the mucus is dissolved (about 1 hour usually). Following centrifugation a wet film 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 Bonnet (19,ili. Throe or 4 cc. of selected portions of sputum arc placed in a centrifuge tube ami 2 or 3 times this volume of 3% caustic potash is added. It is then shaken ener getically until the mixture is homogeneous. Ilcat to the boiling point is now applied. Rapid cooling follows and the mixture is centrifuged for ) to 1 minute. The supernatant Uuid is poured oil and the deposit placed on albuminized slides and allowed to dry. After being lixed with heat the films arc 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, 192S), the other a variant of Rappaport anti Ellison's (1D2S-192D) modification of Weigm's stain. In Alcthod I, Barth's orcein stain is heated to 55 C. and the slides immersed. They are kept at this temperature for from l to '2 hours, and are then washed ia water, differentiated in acid alcohol (2 to 3% hydro chloric acid in 95% alcohol), washed again in water, dehydrated in abso lute alcohol, cleared m xylol and mounted in Canada balsam. The elastic fibers arc stained a dark reddish purple. In Method II, the hhns are immersed in Weigert's stain, as prepared by Rappaport and Ellison, for a period of 20 minutes, following which 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 libers are stained a deep blue-black. The relative merits of these two methods of staining are as follows: Tinstain as used in the Barth method is relatively easier to prepare, and once prepared can be used for an unlimited time, while the modified Weigert a stain, besides being far more difficult to prepare, tends to deteriorate much more quickly. On the other hand it stains clastic tissue in 20 minutes, whereas the modified Barth method takes from 1 to 2 hours. The final result is equally elhcient and each can he used as best fitted to the imliv dual laboratory. IS l ' w ' . r . : n i m ' t i w i x m . M n x u i v \ n i u -x t o k i T a u i.l 1 L i.s r o r C \> rs . Sputum . .it tim i' i>f -`p ittm n ex am ination. 3 Z 33 1 V 4 2 *25 M .ittrt-- n m k im : 1 2 I M 3-1 3 <3 Spinm-r tj Always vibj <l tu c a ta rrh . U>eiitcen ray n rcn tiv e fur 1h>tIt lull ri u k ^ ia am i a-dx-Mous .3 _ _ -- Ni> definite iC>-utticn ray e v id t tn e of asliestusis. 1 \ -- '-- -- Now, 2 n irs later, apparently m exeelhnt health. . (> \ er> mil! likm.-as, continuuU d d ry ha kiuj' couith. i -h 1 - - 3, M : 7 ! Sull 7 Ijte illc tit In a lth ; no 'otuili. *2 - | i 36 4 1M ! Ofhee worker io Office ! empi. ' S u ll em pi. IO Excellent h ia lth ; no m u c h Now, 5 y ears la te r, s till mi excellent health. j + ;' ! i 5 ; -p ; - _ i 2S w orker 5 F . 27 i 1 F ! -< 10 , Spinner 6 1 Teaser ta a J n iriiiT Stili em pi. 1 4 lo C old, couch iM stritn , th o u g h t to lx- due to :edx">lns dust: definite jaundice. Pulm onary us be* mats. IO D chm ic proitre.viue b.isul fihroois. i 5 Id -r ! -- - 9 i + - 1 1 7!M ! u i* j 30 | E very IO iA ihtionary tulierculoM.* su p erim p o sed <*u .tslx-stosia. D + -T ' + + Confirm ed posuuurtc-in 7 m o n th s late r. 1 8 M ; dept. u 4 l3 Bilulc-ral aslx-stosts w ith asso ciated Uiljcrculoais. i ' 45 Confirm ed (XMiinortein l >cur h u r 12 , + J + 9 1 M 1 1.11 S u ll 14 Bildtcr.il p u lm o n ary oalx s to sis with -.miiM-dcd I 37 ; Associate! empi- tm pcruddid tu b ercu lo u s in filtratio n of upper me i With UiOefi , 1.it rk of n^bt lum; , 14 ; + + 1 + _ 10 M 46 Just { 12 3 W hite 15 No d a ta 12 , + + - _ Died of p u lm o n ary asl* ?t>&i.s with sui>crjm|H>sel Just j tulx'rc-uhois 3 years later, confirmed postmortem. 11 F 11 1 3 31 M a ttre a s . m aker 12 V 15 ; 1 31 M u t i n e ' m aker Ib A dvanced p u lm o aary .slxnUiuid, b ro ii'h iits and cardiac failure; continued jxistinorti-m | lb u . IO ProKrcvjixe puiuionary' aslwalowis f mud rate ! seventy. 15 + + a ! + Sum Lit s ta te . i 16 + + ; - -- 13 F 44 1 . 16 17 Brorn h ilts. | 17 -- : + ji - 14 M 55 15 1 Sptnner ; 1 IO Em physi m a w ith d y sp n ea, ism clt and pnm m , abtiouu n. ; 12 + + + i - \ cry ill, curb) o f l u r ( ->). L a fir lnj)ar>iomy w:us done; <1a th followed. 15 ' + + + : - 15 M is ; j 30 \ orenoD 13 Pulm onary lid * reulo-us am i oslx.sto-.i-*. Confirm* d by postmru in 1 yar later. 17 + + 1 - + ! m atin ss m aker 16 M 0 li 18 Pulm onary aa Lewis com p In a led by tu b r iilteua IS + + j + 43 17 M 20 (?) T u U rculosia plus jalxstoM S -r t -- ~ (7) Spimi r 18 K 18 3 i l Progressive pulm onary ,wdx -l-os with lardiu' 35 M at trevi involv* im. n l. idd + ' - m aker Died 1 yar later following pruenam y ami parturi tion. 19 F :i 6 ; lt> M attrrvs 22 KiC.hl-oiih d baaol ph oral t In ki mm:, dy sp m o . ' c o u c h . ml* rcle* auspectci 1, tul* rm ilo-ts is>nliniiid i o + + + : + -h m aker l P rim a ry pu lm o n ary .e->latiii.sia with mi|h rimpo-u il 1 a etix c tuL.r n)*M:. 20 M 17 2 22 Pulm onary osIx-iUx-is 47 M d ttrc v i Propri ^->i\. p ulm onary aal* st>is -+ + 1 + + Id + + - -- 22 + + + _ m aker ' 21 F 6 ! 15 45 M aU riaa 23 Cerebral aoficnin. acute hronelntis and bnintln*- p lin iin n ju .i w ith a-ii iat> d ;cd>esloMx. 23 ! + + ~ m aker 22 F 19 ; 4 41 M a lt resa i f/i.ikt. r (>titirmd Liti r larstin o rtem . 21 ( 'm ath, d y x p tu a; vi1it . of b.is.il ilbnisi.s by H<x oliti n ray x;uiim.iti><i> 21 D eath from at nl- uillu n / a 2 year lati r. ! !- : - _ 1 * Kbe-du* tidin' present (C.ws r>, H. '20) p \ r ,v .: * p i t i \i \ p i i .\1o v \ h v \ ^ pi v l *o ^ n T m h . i. I - --I , i -*r >i* ( ' \ n ).* --1 'o n 11 'i Hi'il X~v v: z T ti 2 ( Mum nl ,u m i ' i>i s p u t u m - r f 4- c k - ' -~ - - - ill y , , MU M .itir. " 21 MiM puinn'n.irv I d .r.i'i' Pri-Ltri -v-\r pulm m m r) .ud* - t 21 - --- inukrr 21 F 1 1 1 21 I'ulrnoii.m .udx sli with Oil* n ulo'is 2 1 \-- -- -- 57 .''piiutt r A-l/* - t. e p with ( \ I i i i s i \ c p litlu Is i .nbrni' <i 1)\ I - `stnu>rti m 1 \> nr l.m r 25 . F 41 16 \J n ttri '.t M 27 'tt.u i i.f pl> ir.il i-lTu'Uiu I'ruL'n-'iM - puliiK-n.irx ,ud * s(<>-i:- 22 - f - 25 T ---- m:ihi r 1%w> i :u s i.t b r .n 1\ .io n <1 .t'lx s i'-!', tit) cuintli. 2t> F n 10 i'J M attr-^ m.iki r 27 Y 21 2 4b M .tn n " 2d I'ultmui.ir'. .L'li* 't i i 'i ' 21 -r ---- l in 1`in p l`i .in Mintlinonarv a.d.rstosis of proim um-nJ 'i \,i rt\ 2i l -- -- -- 20 l'r>n:ri-"iv* |>nt)it>ni.irv .t-'lit.-lo-i' 2i ~- -- -- l in <Mij>h* .itii piilntiut.irv .t-lx'st<>sis _",i; ------ -- -- 2$ M 63 ni:iP r ht ('a.-diter M ill , 10 V, r \ ' \ i n (ouylt, d> 'p n r a ; mild pulm onary .l-Ix's- tl>s)s 27 Pu lm o n ary .t-Ustisi^ anil tu ln r tn io 'H to n h rtn rtl ---- lali r {M.stmi.rii in do --* T -- _-- 20 M :$> S till 3 5 G imh ral eoiwlitnm f.urlv i*l. .15 T - r -- 1 o o W arehouse tMJlpl. m an 30 F 51 67 M a u re r 4 3 5 F .u rk a iK a m t il fil>riMs (Uin-ntL'en r.i\ cxaininatiom 26 + - -- -- P rtm rrv u u : um uuipln .m 1 puhnon.w \ 51; _-- 31 M m:tkt r 0 50 A iivam xl pulmonary fibroin. 50 r _ 6 3 H l* .r r-jp th-pi. t Lmn: juu-o { i:U>tc ll.-s^uc not pri m on n .iti .l ci .uinn.il ions l( _**i. 2 i . Analysis of Cases. Tlic present study includes .`18 cases of asbestos workers of whom 81. where full details are available, are recorded in the preceding table. The eases have been arranged in accordance with the period of time that has passed since they first became exposed to asbestos dust, whit h in several <ases is not equivalent to the actual duration of exposure plus the interval since leaving em ployment, since some were t mplov ed iu eyul.uh or v eie absent from work on account of child! >nill, service overseas, etc. Twent\-one of the i.oes are males and 17 females. M`he aye at which they beyan workiny in an asbestos factory ranyes from 18 to 39, averaye 21, but 17 of the 81 recorded in the table beyan work before the aye of 21. The averaye duration of exposure is 1.7 years, with a ranye from as low as 1 up to .70 years. M'uberculosis wa-' present in .8 eases, and in this yroup the averaye period of exposure was 9.2 rears, as contrasted with lb years in the non-tiibereulmis yroup. (,'a.se 28 is exceptional in that lie was not really a worker in asbestos and he is therefore not included in the averayes yiven. Sputum Examination. J.vh'sfo.v bodies have been present in every ease with the exception of Case 1, a woman, ayed 2.7, who was in contact with a minimum amount of dust as a mattress maker for ( 0 i i r n m in i t i .m o w u v . m m v r n s i s jc.iis, tiie whole period hcinrc Mib.wi nrnt to the abolition ol the lev method of manutaeUnc. She has always been subject to respirttory tract catarrh, which may have been a factor in preventing aitry of dust to the lung alveoli. With two exceptions (/.'uses l md 5) bodies were demonstrated at every examination. In Case 7> he spntmn was negative after f> years' exposure but positive (a solitary body only) wdicn examined after 11) r ears' exposure. Tito number and type of bodies were most variable. Generally the large beaded or "weathered'' type of bodies, deep brown in color and strongly iron-rcaeting, were most prevalent in eases 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 only been 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 bceome in consequence both darker in color and more strongly iron-reacting. Clump.? or groups of bodies were present in 10 of tlie eases. Five of these had tuberculosis, of whom 3 have died and the other 2 arc critically ill. One of the remaining b 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 Gcases (Nos. b, Hi, 21), 21), 27 and 30) the spntmn was examined for elastic tissue by the methods described and a positive result obtained in 3. In Case b a solitary ''weather-beaten'' asbestos body was discovered after 10 years' exposure, yet elastic tissue was present (Fig. 1). In Cases 2G and 30, bodies had been found on several former occasions but neither clumps nor tubercle bacilli; elastic tissue was absent from both In ('uses 20 and 27 clumps as well as single bodice bad been found pre\ inudy but no tubercle L l g k n o s t o i l F lU S . I TO 7. F i g . 1.-- Ca.sc 5, F , ago 25. E la stic tissue in s p u t u m of n-sixstus worker. T r u y e a r s ' ex p o s u re to a s l x s t u s d u s t . O n ly o n e *' w e a th e r - b e a te n * ' b o d y fo und, no dumps, no tu b ercle ba< itii. X 300. F ig . 2 .--Case 20, M . ago d7. Elastic tissue in sp u tu m of asbestos worker. T w e n t y - t w o yo urs sin c o n se t of ex p o s u re ( d u r a t i o n 17 y e a r s ) . Asl>Cstos bodies a n d c l u m p s p resen t, b u t tur tu Lcn h: baci l l i . X 300 F iq . 3. -- C a se It). M ., age -13. E la stic tissue in case of as bestosis w ith t u b e r culosis. E ig h t e e n y e a r s since o n se t of e x p o s u re ( d u r a t i o n t> y ea r s) . E la stic fibers, asbestos bodies a n d clu m p s (lug. 7) a n d tubercle bamlh all present. X 300. F i g. 1. -- E l a s t i c t i s s u e i n s p u t u m of a pun* c a s e o f p u l m o n a r y t u l x ' r c u l o s i s . X 300. F m x . f> a n d (>.- - C a a o 2 8 . M , a g e t 3 E l a s t i c i i s s u e in t a s o o u s m a t e r i a l m a p h t h i s i c a l c a v i t y < h v se o f p u l m o n . u y Lu I h t u l o a i s s u p e m n p o a il u p o n a s t n ^ t o s i s i n t e r v a l sin ce o n se t of exp o su n * 30 \c a rs X 31)0. I'm . 7. C ,u c 10 '"'m ail c lu m p of .sU stus U>dn a m s p i d u m , from sa m e ruse ns Fig 3. X 300. >-'v ? S f$ f 'S. "N s r t T i 'M in in *i,m o \ v u v x m u s t o ^ k Vr- *vW?l t I . ; v* K J jr -. '/f 'V V\ s < \** V Ku \ u) i . 1 M T T C U l \ I T I . V f o V \ i ; v a .-- 1 I 1 : i s l . s icilli; elastic tissue was demonstrate! 1 in 1C';im` 2U (!'i". 2). hi 10 , cllini] >s, tubercle bacilli and ela rstie rr. WtTi- ;tll priMHit and 7). '1 hesc res nits a re simini; iri/iM1 in T iiUe'2 T \ ui.i. 2. --(*\"T Kx \ mtrskt) i on Ki.tiiic Ti-'I r. ('A* No l>o<Jf<t. 1 U salle, '1itl.l-M!> 1>.i<til) T) - -Ml> - -r -- 11 *r T' + i- Jit ~h h -- Jl> + -- -- -- 27 + -r -- -- :sn -- -- -- Discussion, T h e findings here rt.-jji>rt<n! hit lor lire mu-.t part in accordance with those of other worker-' and show that the mere presence of asbestos bodies in the sputum of an individual denotes nothin;! more than that he has at some time been in contact with asbestos dust. T h e 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 lias heen in contact with large quantities of dust over a long period or there is some underlying pathologic condition of tlie lung, leading to gradual liberation of accumulated bodies. This is illustrated in Cases 14 and Ilk In the hunter the sputum upon repeated examina tion showed large numbers of bodies, the individual in question having been associated at the time of cMumuatiun and for lb years previously with large quantities of dust, (.'use H), on the other hand, also with numerous bodies on repeated examination, had only been directly exposed for a period of l> years and bad not been in contact with dust for lb \ ears 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. T h ey were found by Siuison (11)12!)) in the lungs of a patient who had been expo-ed lor 2 mouths only, and by Stewart ( t*).'>()) in a guinea pig after b months' exposure in an asbes tos factory. Once formed, tlice can iemain in the lung for an indefin ite period. In a patient of Kllman's (l!)bb) exposure was for 10 weeks only, and 5 years later bodies were recovered from the sputum. In Case l-> of tliis series, the patient had worked in asbestos for 1 year, and 7 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 In slow dilfusion out of silicates ) from the central filler and their interaction with constituents of the .surrounding body fluids. It follows tlu t bodies of large size in the ]i sputum indiiate that t h e s e have formed around libers minded mimv rears bclmr. On the other hand, small, thin bodies, though doubtless of recent foim ation. aie no indication that their central iibi-i s have heen m o n t h inhaled `Turing" bodies may lie en * >b., 11-i>, Inn 1 no i>pportunity I'M.I.: -IM'Tt M l \ IT U In V U lV M llS T f H - , dI' inhaling diist for main .war?,, and u is known that nsbeys libers \na\ remain in the lung I'm- long periods without mvessanhy becoming comvrted inlo ''bodies" at all. Another >oint of great importance is (In; so-called ratlii-rinL of the asbestos bnd\. Many of the old large bodies present a dis tinctly rugged or ueather-heatni aspect. often consist ing, as it were, of widely separated irregularly shaped heads strung mi the fibrinm core. There can he little douht that this process is associated with .solution and disintegration of `'body" .substance and accounts, in my opinion, for the interesting finding of Fouwcuthcrthat the silica content of (he (ibrotie portion of the ashesios limy is mneli less m workers who have been away from dust for many sears than in those reicntly or still in employment, even where the length or exposure has been the same. "Wealbenny" is probably a constant process in these eases, hut may he accelerated In the occurrence of caseous or suppurative change. The elump-like arrangement of bodies within the limy alveoli was observed from the very outset of detailed histologic studies (Stuart McDonald, 1(.)27). When the presence of chimps m tinsputum was first reported by Stewart, Tuttersall and liaddow (l!)o2) if was suggested that tliis finding w;(s a clear indication of disinteyiatioii of limy tissue, whether by a process of simple sup purative bronchopneumonia or a s`a result of. a secondary tuber culous infection. In either ease it was legarded as being \uuudly diagnostic of an underlying nsbestosis. In the present study, lit cases in which clumps were present in the sputum tend to substan tiate this view. Four of them suH'ered 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 "> eases, 2 have died, 1 of cerebral softening, acute bronchitis and bronchopneumonia, the other of bronchitis and cardiac failure, both with underhiny asbestosh. The remaining '! me sutferiny with definite progressive pulmonary ashesto.sis, fully confirmed by clinical and radiologic examination. Winle the presence o! asbestos chimps m the sputum is prnbabh indicative of limy destruction, the converse is by no means true, that is, the absence of asbestos clumps allord.s no assurance of pulmonary integrity. Then: are many eases in tile present scries in which there has been definite disintegration of the lung and yet no clumps have been demonstrated in tile sputum. Other possible fallacies exist. Afore 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 underhiny pathologic condition in the lung may have led to chemical or physical dissolution of the ihunplike anangemt-nt so tiiat when expectorated in the midst of caseous materia! or pus, the (lumps may have di .integrated into their individual fibers. 1 PAOK: SPUTUM IN PULMONARY ASUKSTOSI.S (irilncr and Cummings (198!) state that in guinea pigs tuberulous caseation cansos the asbestos bodies piescnl to lose their ;oldou-yullow colur; they also tail to give a Prussian blue reaction uul later are apparently so completely disintegrated that not even i supporting fiber remains. Elastic tissue in the sputum, irrespective of the underlying pathoogie condition, has long been accepted as unequivocal evidence of ung disintegration. Rappaport (1929-1980) memions that elastic tissue may appear in the sputum of patients who present only very mild- signs of cluneal activity. lie 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 \\ liieh clastic tissue has been demonstrated in the sputum illustrate several points of interest. In Case 5, the presence of the clastic fibers is dillirult to explain. SIic 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 asbe.stosis to have developed. Yet 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 ahacillary or prebacillary stage could not be excluded. In Case 20, the presence of elastic libers is associated with a rapidly progressive form of uncomplicated pulmonary asbestosis. In Case lb, the presence of clastic 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 l 'iguies b 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 1G. 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 tuberculosis. The incidence of tuberculosis in this scries is therefore 21%, exactly the same as that recorded by Wood anil Cloy no (1081), lmt less than figure given by Filman (1920-1981), b out of 17 eases. Fridge (1981) reports an incidence of 31.')% in fatal eases. 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, hut their absence does not mean that disintegration is not in process. 1 P l - w t i c f i b e r s arc nri >1 . ' d d \- im lira 1 1 v r o f rapid l u m ; d f s t r u c t i o n . p a i ;K : A C K T y ,-3-mk t i i V i.cn oi .i n 5. Klastio libers may bo p ru sen t in tin; sputum in pun- pulmonary a.slxwtosi.s 1>otli with and without dumps, or in asbestosis' with associated tuberculosis. (i. The routine examination of the sputum in eases of suspected pulmonary asbestoxis is essential, as it plays a significant role in the clinical diagnosis. T wmh tr> e x pre ss m y MitfiTf a p p r o d a t ion In P i o D ^ o r M . J . S(,-w :irt for t hr m o of h i 3 p er so n a ll y collet ted m a t e d .d . hid fr i e n d ly c ritid > m a n d able ad\i< e. un d e r whose gu i d a n c e (.I113 p a p e r h a s U v n w r itten , a n d to the B i i h s h M e d i c a l Ro -r.in h ( u u n e f l fo r finan cial as.->idani o. T a m also ind e bted to D r A f \ 11ad lo w a n d D r X T utter '-n ll for the use of their cli n ic al an d rad iological m at erial, a m i to M r. L a w ^ m for Ida te< him al u.^iatam *. REFERENCES. Bridge, C.: A n n . R e p - Senior Met). l iisp e e to r o Var toiied. I*. 71, 1941. C a lm e t t e . A.: L 'infoction bacillaire u t la tuber cu loso . 4 r ed., M a d o r i , Paris, p. 490, 192S Cook e, \V. E .: B rit Mod. J.. 2, l 17, 1021. Ibid.. 2, 102 1, 1027. E ll m a n . P .. Pro c. Bo y . S o r. Me t.. 24, 520, Al l . a n d l>90, 1920 1021, J. Ind u st. Hygiene. 15. I t o . 1944. F o w w v ath o r. F . S.. P erso n al c o m m u n i c a t i o n , 19-41. G a r d n e r , B. U-. a n d C u m m i n g s , D . K.: J . I m lu s t. H y g i e n e , 13. t'*5 a n d 97. 1941. G en tz. C.. a n d B o n n et, K.: A c t a Moil. S c a n d i n a v ., 75, 42-1, 1041. G lo y n c, S U - J I m lu s t. H y g ien e, 13. S'>, 1931; L a n c e t , 1, l .M 1032. K ru g er, K., R o d o s k i . ()., a n d S a u p e , E . . Arch. f. G e w e r b o p a t h . u. G ew erb ch }g , 2, 55S. 1941. L y n c h . K. \ I . . a n d S m i t h . W. A.: J . A m . M e d . At>sn., 95, t59. 1940. M c D o n a l d , S. : Brit. Med. .1., 2, 1035. 1025. Me re wot lier, K. R . A.: J. I m lu s t . H y g ien e, 12, 19S, 1940; T u b ercle, 15, 00, lOO a n d 152. 1044-1941 R a p p a p o r t . I.: J. L ab. a n d Clin. Mod-. 15, 1, 192 9-1950 R a p p a p o rt, I., and Klli-on, R. T .: Ibid., 14, 201, 192S-1929 Simaon, F. \V.; A na. Rep. So. A frican Instit. M ed. Res., p. 01, 1929. Sim son, V \V., a n d St r a d i a n . A. S .L P a th , a n d Baut , 34 l. 1941, S te w a r t , M. ,1.; Brit. Med.. J 2, 5S1, 1020. J. P a t h , a n d B a ct., 33, M 'y 194t). J. T e d i M tO h o d .s an d Bull. I n t e r n a t . Asm i. M e d .MiiM'imia, 13, 70, 1941. S te w a r t, M. J.. a n d Il.iddow , A. C.. J. P a th , a n d Ihu t., 32. 172. 10_.'9. S t e w a r t . M. .1.. 'Vat tors al. ami Hmldow, f Ib id . 35, '.2 1, P.) >2. B ooil, B". Ib, a n d G loyne, S. R . . Ib id , 2, 051, 1941. ACETYL-j-METHYLCHOLIN (MECHOLIN). OBSERVATIONS CONCERNING ITS ACTION ON THE BLOOD PRESSURE, SKIN TEMPERATURE AND THE HEART, AS EXHIBITED BY THE ELECTROCARDIOGRAM OF HYPERTENSIVE PATIENTS. A SSO IT VTK B y I r v i n e II. P a g e , M .P ., IN' M K D IC IN K , I l O S r i T M . O K T I I W I t n f K h r K t .L K I J K O H \ I U ) | ( ` U . i l F S K M t r t f , N K W Y O U K , N'. Y. iNStTL'l TK Hi, NT \Ni> T w K i i i 1 were tho firnt to prepare ;wul ih tt'rnhne many of the pharmaeologie properties of aertyT/-uictliyleholin. TSI:ij(uaml Cline- have synthetized it (" inecholin") by a proeexs wliieh lue imuic it available m quantity. Kecently studies of its pharmaeoiogy