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BFG17432 18 R. K. French 11 Litlrc. E. (Iran*.) Oeuvres Compfe/es d'Hlppo crate, vol. I. Paris, 1839. 12 Chadwick. K. J., and Mann, W. (irans.) The Medical Works of Hippocrates, Oxford, 1950. 13 Castiglioni, A., A History of Medicine, 1947, p. 136. 14 Ncuhergcr. M., History of Medicine (Irans. Play fair, l*.)\o!. 1, p. 116. London, 1910. 15 The Historia Animalium was designed to give an account of the characteristics of animals, and De Partibus Animalium conducts an investigation into the causes of these features. What Aristotle has to say on the soul is found largely in De Anima. Aristotle's works are conveniently con sulted in the English translation of the Oxford edition. 16 In particular in his De Usu Partium: see the English translation hy May, E. T.. Galen on the Usefulness of the Ports of the Body, Cornell University Press, J96S, 17 Thi* has been translated by Hurihult, F. R., `perl Knrdies*. Bull. Hist. Med.,1, (1939) 1104-1113. 18 See l*o>d, G. E. R., Aristotle, Cambridge, 1968. 19 Historia Animalium 496a, 513a. De Partibus Animalium 666b. 20 Quoted from Cole (1949) p. 39. 21 Historia Animalium <96a 20 note 4. 22 Historia Animalium 513a. 23 In De Somno et Vigilia 458a, the aorta is Mid to be connected not to the middle cavity but to one of the side ventricles. 24 De Partibus Animalium 667a. 25 Wilson, L., 'Erasistratus, Galen and the **pncuma** \ BJl.M. 33 (1959) 293-314. 26 See also Historia Animalium 496b. 27 Aristotle says 'even the two small (cavities)* have channels to the lungs. Historia Animalium 496a. 28 Platt, who makes the suggestion, extensively re stores the Greek to get an answer to the problem. Platt, A., `Aristotle on the heart', in Studies in the History and Method of Science, edited by C. Singer, vol. 2, Oxford, 1921. 29 The anastomosis between the vena cava and aorta apparently described by Aristotle is not dealt with here as it seems dear it k a textual corruption. The reader R referred to the notes by Ogle and Thompson for further details of the various attempts to interpret Aristotle's statements on the heart and vessels. 30 Lloyd (1968) p. 74. 31 There is a possibility that the vena azygos may have been represented in the traditional accounts and Thompson thinks that the vein here des cribed by Aristotle may be bused on an imperfect know ledge of it. 32 historia Animalium 511a. 33 De Partibus Animalium 666b. 34 Harris (1973). 35 De Partibus Animalium 669b 15 note 2. Requests for reprints to: R. K. French, PhD, Director, 'Wellcome Unit for the History of Medicine, Univer sity of Cambridge, Free School Lane, Cambridge. MjatJOL Thorax, 1978.33, 19-25 Polyvinyl chloride pneumoconiosis1 A. ARNAUD, P. POMMIER DE SANTI, U GARBE, H. PAYAN, AND /. CHARPIX From the Clinique de Pneumo-phtisiologie, HSpital Sainte Marguerite, Marseille and the Laboratoire d'Anatomic Pathologique, Hopital de la Conception, Marseille, France - Arnaud, A., Pommicr de Santi, F., Garlic, L., Pavan, H,, and Charpin, J. (1978), Thorax, 33, 19-25. Polyvinyl chloride pneumoconiosis. A 53-ycar-oId man, who had been exposed for 23 years to polyvinyl chloride (PVC) in the bagging area of a vinyl chloride polymerisation plant, presented with a diffuse micronodular infiltrate on his chest radiograph. Light microscopy of lung obtained by drill biopsy showed a diffuse infiltration \yith histiocytes and mullinuclcatcd giant cells, with some collagen formation. Ultrastructura! studies showed foreign particles in the macrophages, which were identical with PVC powder viewed under the electron microscope. Incubation of PVC powder with human lung macrophages in vitro showed that the macrophages engulfed the powder to give a similar ultrastructura! appearance. Pneumoconiosis due to polyvinyl chloride (PVQ was first described by Szcnde el at. (1970). Several epidemiological studies have since been made, which lend to demonstrate that PVC or vinyl chloride (VC) inhalation may be responsible for abnormalities of pulmonary function and chest radiograph (Lilis et al,, 1975, 1976; Miller et a!., 1975; Suciu et al., 1975). However, histopathological descriptions of this disease are infrequent. We describe here one such case and a study of the ultrastructure of a lung biopsy specimen. Out report A 53-year-old man was referred in April 1974 for investigation of diffuse micronodular chest radiographic abnormalities (Fig. I). He gave a history of chronic productive morning cough for three years, and for three months he had noticed mild weakness and slight exertional dyspnoea. He had smoked 20 cigarettes a day since age 22. The patient had worked from November 1945 until December 196S in the PVC bagging area of a vinyl chloride polymerisation factory. Since 1969 he had worked as a shepherd. A chest radiograph performed in 1968 as a routine factory check-up showed the same micronodular shadows. No fur ther investigations were done. Previous chest radiographs were said to have been normal. Physical examination was negative. A scratch 'Supported in part by (I* Inititut National J< la Santi c| l< la Rechcrwbe XiiAcale tuberculin skin test was weakly positive. Sputum examination for Mycobacterium tuberculosis on three specimens was negative. The red blood cell count was: 419X10*'/l; haemoglobin 13 2 g/dl; leucocyte count 6-6X10*/! with 40% lymphocytes and 60% neutrophils; platelets 294X10"/!; erythrocyte sedimentation rate 6 and 20 mm/h; cholesterol 2*11 g/; total bilirubin 6 mg/1; serum alkaline phosphatase 53 U/l; SGOT 25 U/l; SGPT 39 U/l. Pulmonary Function tests showed forced vital capacity 3-S2 l (expected value 5*29 !); forced expiratory volume in I second 2 82 1 (expected value 3 S9 1). Arterial blood gases: Pao* 84 mmHg; Paco. 40 mmHg: pH 7-39. Carbon monoxide transfer factor 32*14 ml/min/mniHg (predicted value 31-75/mI/min/ mmHg) 5*0-7 mmol/min/kPa; 106 mmol/min/ kPa). No abnormality was seen on bronchoscopy. A lung biopsy using Steel's pneumatic trephine was performed. LIGHT MICROSCOPY The lung specimen was, for the most part, diffusely infiltrated by histiocytes, in which were seen a fewalveolar ducts (Fig. 2). The cytoplasm of these histiocytes contained clear vacuoles. Giant multinucleated cells with vncuolateJ cytoplasm were also present (Fig. 3). PAS and alcian blue stains were negative. Polarised light revealed no intra vascular birefringent particles. The cells were arranged in a collagen matrix, which was of thinly fibrillar aspect: a few smooth muscle fibres were also seen. WIU'TO! 2199G0O1 A. Arnauil. P. Pstmmier it Sttnti, L Carbe, H. Puyan, and J. Charpin Polyvinyl chloride pneumoconiosis **,. ' l ,, ;. . * Fig. I Chest radiograph showing disuse . micronoduiar Infiltrate. 21 BFG17433 Fig. 2 Lung biopsy shmving diffuse infiltration with histiocytes. (Jioemataxyiin and eosin XJfi) Fig. 3 Clumps of histiocytes and some giant cells showing a finely vacuolated cytoplasi ELECTRON MICROSCOPY The specimen was fixed with 3-4% glutaraldehyde in a cacodylate bulTcr; post-fixation was with 2% osmium-tetroxide. The specimen was then de hydrated in acetone and embedded in Araldite. The sections were cut by a Reichert ultramicrotome, then stained with uranyl acetate and lead citrate. Examination and photographs were obtained by Philips EM 300 electronic microscope. The cytoplasmic membrane of the macrophages had thin expansions; the nuclei were small, and chromatin was either irregularly disposed in clumps in the cytoplasm or placed against the nuclear membrane. The cytoplasm was, for the major part, infiltrated by a non-homogenous material surrounded by an electron dense mem brane, whose outlines were irregular. This material was either granular or of a fluffy appearance; the granules were 0 3 to 04 microns in size (Figs 4 and 5). Between the phagosomes, thin cytoplasmic layers covered the organelles; the mitochondria were small in size and had well conserved cristi. The Golgi system was normal. These grains were connected by.PVC bridges or by the interposition of smaller granules of 0 1 micron diameter (Fig. 6). Phagocytosis of PVC powder by olveolcr macrophages Human alveolar macrophages were obtained by bronchial lavage. About 2 to 3XI0'; macrophages were incubated with 0- ml of PVC ponder for 90 minutes at 37*>C in a mixture of 20:1 of compound 199- and 80% of feta! calf serun'.:. The macrophages were then treated and examined with the electron microscope according to the method previously described. The absorption of the PVC particles in the c>top!asm of these cells was rapidly accomplished. The particles appeared in the phagosomes as cither oval corpuseules cr clusters which were variable in size (Figs 7 and S). At this stage, the panicles showed no evidence of degradation. Thinly granular hsosomal material was deposited against them. The cjioplasm of the macrophages contained mitochondria, bundles of microfihmcnis. and multiple bsosomes. Electron microscopy of PVC powder The PVC powder1 was composed of oval grains. whose size varied from 0-5X03 to 1X0-3 microns. `AFCOVYL11, rcchincy. W Saint Auban, France Discussion In this case of discrete pulmonary fibrosis ass4.vi- Mnititut Piutur, 75 Pari*, France 21990002 BFG17434 n.r^Ui E0006GT2 0|nurj3 |c.vj durAsq suo;s3| .n|l uoiicujiucx* i.'iq uq spoqioiu |>*nsn ?qi. ,\q pAUins ion .'J.'av qjiqn s.'>|nucj3 ?imsriJoii.TJiui Jinujiu pomci uio sum wqj. sj|3P poic.-q.uiuiiimu uc;3 puc SAjcqJOJJClU JO pOSOdlUOO |3A3| jqO.lqC 1C UO|l oroi jpijjcs uc pAoqs s3;J-cou|n3 oqi jo uojicuj jjcvt] pj55cq sc.w JApvod ^.\J JJcqvs iuooj * ui sqiuoui ujaos 01 o.wi uiOJJ situ puc sSid-CJUjnS pcsodsi O'jn '(r^l) '1 13 C|5uoj;j -<q poqOA -ojJ a'uciuciuujJa'J csoq] sc dues cqi sic suo;so| OS.^m. SJptUCd ICUOUqod JO pjOAO pjuicjuoo S|J33 ssoqn suo|so[ snoicuio[nucj3 |C.toj qiiw pcicnossc stsoiqij osnjj;p pnuoqs (sdoiq .Ucuouqnj sjn]|cj AjoicjjdsJJ 5J5AJS pcq ludicd siqx OAd jo spAaj q3jq 3u;u;riuo3 lUCUiuojjAUO uc ut sqiuoui Zl joj p.iqjo.w pcq oq.w uciu pio-jca.t-if c jo csco cqi p.iuoJjJ oqAv `(0461) 7 >3 opuozs 3q popjoo -3J Jsoqi qiin jcouuopi ojc oqijjsop o. suo|S3| IcoiSoioisiq cqj_ SA\opcqs oiqdcjSoipcj issqo jcinpouojouu jo/puc JtqnouoJ JAcq sjca.( OZ iscjj ic joj isnp 3/vj 01 qjo.vs jpqi ui pssodxs sjjqjoAv jo %9-Sfr 1CIH povioqs sjoqinc csoqi `(iL6\) 1 t* sqn <q psqucssp osoqi sc siucs oqi 3JC s|U3|icd jno ui SAiiqciUJOuqc ojqdcjSoipcJ issqo 3qj_ uoiicicqui Z0A.d 3q poonpu; sisoiuooouinsud sq .<cui Siqi icqi iss33ns 3f\ sujcis icnsn sqj itq poyuuopi sq lou p[no3 qo;qM sspiucd psujcjuoo suois3| sqi uoipcsj snoiBiuo|nuiu3 c qiiM pole (J UJ) (UcJoJoUaJOxjijOJ;JviU3J) .*(--) JOljJlOUt jOWQSOf.f/ jojnt/o/J Xpuy Xq pJputtojjrrt SsiutauiOi *pt/;;;no JOjnSjjJl /;i.h 9-ti ujMurt [o SJtpoq fv*o SutMOqS iZoqiOJlOlU JOjOJXjO uo Xq tr.otx^oSoqd aptuod OAJ lo Spnts 0J1L\-U[ l Jij (ooo ax 3) t-) s33Dt<, "? JV9nj}UOi *JD sutoso3otfj '(zj) iuojqiunu 9SU9p o Xq pjpunojjnt Siuqino jojnSJJJt i/;>m jotjjtvut Xffny !u9utptds Xsdotg 5 *Sy VA /. AT ^W y' . ,;f, iW %I w > vv > 3,? -* v.-v-.v > . . i : 1I.t'.*-'.*. * *\ \ > . . \' :'X` ' V. ^f (006 T/X /Vj) "O) 9So/fo^ '99uojxqns jojnuojt Xffnjf o Imutotua* SJU/oioSoyd piwjino Xjjain?9jjf Xq pdtdnj^o Xjivout tuxojdotX9 9ip :(jq) sn9pnu oujum* ipws p i;;/m iXdohs}H y Sij f000 9fX JV3) (--) JitfOlUt Xq j\(n2oj jjo Xi{i :j?h iqoi/9\ jo sjtunqnt ]0.\O fo tpoiu JtpMOt 9 `Sij s;xo}u&3oiunud ipuojqj jXuiaXjoj WAsri' r'-ssr-ur-4* .* ' -* . ^ Vi' `vi**'s-%?r - ` . , Js.i -T, z' 24 A. Arnaud, f. ^ Scn/i. L.Garbc, H. Payan, and 3, Charpin Polyvinyl chloride pneumoconiosis 25 knee of disease among vinyl chloride and poly vinyl chloride workers. Annals of the Sew York Academy of Sciences, 246. 22-4J. Lilis, R., Anderson, 1C, Miller, A., and Sclikoff. I. J. (1976). Pulmonary changes among vinyl chloride polymerisation workers. Chest, 69, 299-303. Miller, A., Tirstcin, A. S., Chuang, M., Sclikoff, 1. J., and Warshaw, 1. (1975). Changes in pulmonary' func tion in workers exposed to vinyl and polyvinyl chloride. Annals of the Sew York Academy of Sciences, 246, 42-52. Prodan, L.t Suciu, I., Pislaru, V., Ilea, E, and Pascu. L~ (1975). Experimental chronic poisoning with vinyl chloride (Monochlorocthene). Annals of the Sew York Academy of Sciences, 246, 159-163. Suciu, 1., Prodan, L.. Ilea, E., Paduraru. A., and Pascu. L. (1975). Clinical manifestations in vinyl chloride poisoning. Annals of the Sew York Academy of Sciences, 246, 53-69. Szcndc, B.. Lapis, K., Nemcs A., and Pinter, A. (1970). Pneumoconiosis caused by the inhalation of polyvinyl chloride dust. Medicina del Lavoro, 61, 433--436. Requests for reprints to: Dr. A`. Arnaud, Hopital Sainte Marguerite, BP29-13274, Marseille Cedcx 2, France. Fig. t In-vitro study of an alveolar macrophage in contact with PVC for 90 minutes. Particles of PVC are eccumulatcdsn a phagosome, which occupies almost all of the cytoplasm ( Smaller phagosomes engulf oval corpuscutes and small granules of PVC. (Af X6SOO) mas. Examination of rats showed more pro nounced initial fibrotic lesions but later lesions were comparable with those observed in the guinea-pigs. The identical morphology of the intracellular foreign particles observed in our patient, and the microscopic appearances of the PVC powder and of the inclusions in human macrophages which have engulfed PVC powder in vitro, arc convinc ing evidence that our case can be considered to be that of PVC pneumoconiosis. Clinically, the evolution of PVC pneumoconiosis is uncertain. Our patient had only a slight reduc tion in vital capacity with no reduction in gas transfer factor, suggesting that the fibrosis was not as yet of much functional significance; on the other hand, Szcndc and co-workers (1970) reported a case with severe respiratory impairment. Occupa tional exposure to PVC! dust may have been dif ferent in these two cases. Our patient was exposed to PVC dust only, while Litis et ol. (1975, 1976) showed that PVC dust Inhalation induced less severe respiratory function abnormalities than simultaneous inhalation of vinyl chloride monomer and PVC. This must be compared with the results described by Prodan et al. (1975), who showed that, in the guinea-pig, two hours* inhalation each day of air containing 10% vinyl chloride monomer over two weeks could produce diffuse pulmonary fibrosis. Further studies of the mechanisms of this pneumoconiosis are in progress. We thank Dr. Allan Towne and Dr. Christian Capo for their help. References Frongia, N., Spinazzola, A., and Duc&rclli. A. (1974). Lesioni polmonari spcrimenlali da inalazione prolungata di PVC in ambiente di Invoco.Sfcdicina del Lavoro, 65, 321-342. Lilis, R., Anderson, H., Nicholson, W. J., Daum, S. Fischbcin, A. S., and Sclikoff, L J. (1975). 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