Document 65ba1LB5xLVXNr802x0d1d8Go

FILE NAME Brakes BRK DATE 1982 Nov 13 DOC BRK075 DOCUMENT DESCRIPTION Letter Published in The Lancet - Mesothelioma in Brake Repair Worker 1101 LANCET NOVEMBER 13 1982 ERYTHROCYTES FROM CANCER PATIENTS AND FROM BLOOD . DONORS HAEMAGGLUTINATION WITH MONOCLONAL ANTIBODY Haemagglutination result Diagnosis Intact Desialated ' erythrocytes erythrocytes No. of samples | GM | mono- cional Ab GM mono- GM | clonal Ab GM Group 1 Leukaemia Hodgkin's disease Hodgkin's lymphoma Myeloma Ewing's sarcoma Wilms tumour . . Bronchus Larynx : Lung Ovary Breast Astrocytoma Leukaemia Wilms tumour Yolk sac carcinoma ~~ Ewing's sarcoma Hodgkin's disease Leukaemia relapse Group II Blood donors Group III Random patients 25/25 4/4 2/2 j 1 1 3/3 1 5/5 1 5/5 1 iy 1 1 1 1 1 2/50 6/50 42/50 4/32 28/32 + + - + + - + + + + + + - - + + +/- - + - - - -~- - - + + + + + + + + + + + + + + + + + + - . - - + + + + + - - id ~ - - - - - therefore unrelated to chemotherapy Control tests showed that a Treatment of erythrocytes from cancer patients or from normal individuals with irrelevant rat monoclonals did not cause haemagglutination b Those erythrocytes that did not agglutinate with anti monoclonal anubody subsequently agglutinated following desialation c Preincubation of the monoclonal antibody with purified T antigen abolished its ability to agglutinate intact erythrocytes from cancer patients d Those intact erythrocytes that could be agglutinated by the monoclonal antibody were not agglutinated by autologous plasma or by naturally occurning anti antibodies This last observation suggests that the epitope recognised by the monoclonal antibody is distinct from that which binds naturally occurring anti antibodies Also although the monoclonal antibody binds T antigen isolated from erythrocytes we have no direct evidence that it is binding to T on erythrocytes from cancer patients Studies are in progress to assess the value of this new monoclonal antibody in monitoring patients on treatment for leukaemia We thank the following from Addenbrooke's Hospital Cambridge and Cambridge University for their cooperation in obtaining blood samples Dr N. D. Barnes Dr V. Broadbent Dr L. Brandi and members of the paediatric oncology clinic Dr J. K. H. Rees department of haematological medicine Dr D. G. Brathenon and Dr T. Wheeler radiotherapeutic centre and Dr T. Gibson regional blood transfusion centre and Mrs Rosamund Svvennson for her assistance in raising the monoclonal antibody This research was funded by the Cancer Research Campaign J. M. and by the Medical Research Council S. M. Division of Virology Department of Pathology University of Cambridge Laboratones Block Addenbrooke's Hospital Cambridge CB22QQ CB22QQ Department of Surgery University of Cambridge Addenbrooke's Hospital JO MILNER SU METCALFE Off treatment GM growth medium erythrocytes surface of their circulating For these studies we first . prepared a rat monoclonal antibody an IgG against desialated human erythrocytes Antibody in the culture supernatant does not agglutinate normal erythrocytes but directly agglutinates desialated erythrocytes down to a titre of 1 in 100 unpublished Preincubation of the monoclonal antibody with purified T antigen kindly donated by Prof. G. Springer inhibits this agglutination Blood samples obtained from 50 rumour patients group and from 50 blood donors group II were then tested for haemagglutination with the monoclonal antibody unpublished All samples were maintained at pH 7.4 and C under sterile conditions and were : tested within 24 h of sampling The results see table indicate that the T antigen is exposed on the erythrocytes of patients bearing a number of tumours including an astrocytoma in 1 case In this group 3 of the 5 samples were negative from patients with Hodgkin's lymphoma and the third from a patient 5 weeks before cessation of treatment for a Wilms rumour Of the 50 blood donor samples 2 were positive and showed slight agglutination the remaining 42 were negative for T. Besides the patients in group , 5 out of 5 patients who had completed therapy for cancer and were off treatment were found to be negative for T on their erythrocytes 1 patient who had a relapse after 3 years off treatment for acute lymphoblastic leukaemia was poA sittihvierd group group III consisted of samples obtained from a patients at random here the samples were tested before checking individual diagnoses 4 out of 32 were positive of which 1 turned out to be a sample from patient on treatment for cancer The other 3 were a year with a poor diet and lung collapse a patient with poor vitamin intake and recurrent stomatitis and a patient with alcoholic liver failure The remaining 28 were negative and included patients with anaemia pernicious anaemia diabetes mellitus colitis splenomegaly pancreatitis liver abscess and : arthritis T The exposure of antigen on the surface of erythrocytes ofcancer patients was detectable at diagnosis diagnosis i.e. before the start of and MESOTHELIOMA IN A BRAKE REPAIR WORKER -Merewether's speculation in 1933 that asbestosis would manifest itself industries including the manufacture of asbestos brake linings where it was then unknown was soon realised In the United States asbestosis was reported in a brake lining weaver in 1940 and the British Industrial Injuries Act of 1948 included asbestosis as a prescribed disease among brake liners Reports of lung cancer in asbestos workers closely followed those of fibrosis but among brake workers such cases at first seemed tobe confined to those who worked in friction product manufacture and fabrication Subsequently there were occasional reports of lung cancer and mesothelioma among workers installing and repairing friction materials However asbestos cancer in brake repair workers has attracted little attention in part because of the belief that fibre remained locked into the brake lining matrix or was much altered by heat generated by braking Dust in brake drums was observed by light microscopy to be asbestos Furthermore the capacity of chrysotile the main form of asbestos used in brake linings to cause mesothelioma may be less strong We describe here a diffuse pleural mesothelioma in a man whose sole exposure to asbestos was to the chrysotile form during brake maintenance and repair A year man was admitted to hospital in October 1980 with sided chest pain and soreness when he breathed deeply Chest ray revealed a sided pleural effusion and cytological diagnosis of mesothelioma was confirmed by biopsy and examination of resected tumour The patient died in September 1981 This man had for many years worked in used car tyre and car repair businesses Since the age of 19 he had serviced automobiles including the replacement of brake linings He had no history of construction or shipyard work or any other occupational contact with asbestos and had never lived near an fabricating plant 1 Merewether ERA A memorandum on asbesiosis Tubercle 1933 15 60-81.109-18 60-81.109-18 152-59 2 Stone M Clinical studies in asbestosis Am Re Tuberculosis 1940 41 12-21 4102 = 4 THE LANCET NOVEMBER 13,1982 1 3 Fig Inorganic residues extracted from lung parenchyma Most chrysotile is present in fibril form fibril A is 0-4 ...mlong fibril B is 5 ...mfibril C is 12-0 ...monly 4-3 ...mis shown Additional shon fibrils are - scattered in matrix debris ee oa Necropsy revealed virtual obliteration of the right pleural space by a tumour that had extended through the diaphragm and metastasised to mediastinal lymph nodes liver and left lung The histological appearance was in keeping with an epithelial type diffuse malignant mesothelioma Slight interstitial fibrosis and anthracosis was noted in the pulmonary parenchyma No typical asbestos bodies were observed but objects resembling such bodies were seen in a stained lung tissue block After ashing only one typical asbestos body was found A tissue mass of 6310 mg was bulk digested.Only 1.33 mg of inorganic debris was recovered 0.02 The residue was immersed in distilled water disrupted by sound waves at 40 W for about 10 and analysed 20 ...l of suspension was put on a carbon formvar support on a nickel grid and allowed to evaporate Another coat of carbon was then placed over the dried residue Electron microscopy showed the residue to be full of exogenous particles almost all fibrous Magnification to 10 000 and more revealed chrysotile fibrils among these particles fig 1 Preliminary identification was based on morphologybut electron diffraction analysis confirmed the structure to be that of chrysotile fig 2 and insert Fibrils less than 1 mlong and others longer than 5 ...mwere present Long fibrils have been frequently encountered in lung tissues from occupationally exposed workers but not in persons with only environmental exposure % of the fibrils were longer than 10 ...m No amphibole fibres were found which was consistent with the occupational history We estimate that about 1 gchrysotile was present per 5 g wet lung parenchyma Although amphibole fibres anthophyllite were used experimentally for a brief time in the United States to our knowledge only chrysotile has been used in brake pads since the 3 Langer AM SelikofIfJ Sastre A Chrysotile asbestos in the lungs of persons in New York City Arch Environ Health 1971 22 348-61 4 Pooles FD Oldham PD Chang UM Wagner JC The detection of asbestos in tissues In Shapiro HA ed Pneumoconiosis Proceedings of 2nd International Conference Johannesburg London Oxford University Press 1970 108-16 Fig Chrysotile fibre bundle in dust burden Selected area electron diffraction pattern insert shows chrysotile structure Reciprocal a axis is marked : 1940s Under certain test conditions of brake failure free chrysotile asbestos can be liberated as shown for example by the work of Lynch Hatch Hickish and Knight Seshan and Rowson Some of these fibres are retained in drum dust and tend to be submicroscopic However besides this submicroscopic chrysotile fibre in brake drum housing there is a more significant source of free unaltered fibre in the bevelling refurbishing and refitting of brake pads There is thus ample opportunity during brake maintenance and repair for contact with chrysotile fibre both in drum debris where it will usually be in a transformed state and as long and predominantly unaltered fibres liberated by machining Controversy over the potential of chrysotile to cause mesothelioma has continued despite evidence from asbestos textile fabricators thought to have used only chrysotile from workers making brake pads from chrysotile miners and millers and from animal studies 5. Lynch ) Brake lining decomposition products 7 Air Pollur Control Assoc 1968. 18 824-26 6 Hatch D Possible alternatives to as a asbestos friction Ann material Occup Hyg 1970 13 25-29 Occup 7 Hickish DE Knight KL Exposure to asbestos during brake maintenance Ann Hyg 1970 13 17-21 8 Seshan K On the utility of field electron microscopy in the determination of the application degree of deformation in chrysotile asbestos an environmental research Enver Res 1978 16 383-92 9 Rowson The chrysotile content of the wear debris of brake linings Wear 1978,47 1978,47 315-21 10 Rohl AN Langer AM Wolff MS Weisman 1 Asbestos exposure during brake lining maintenance and repair Enver Res 1976 12 110-28 11 Rohl AN Langer AM Klimentidis R Wolff MS SelikofIf Asbestos content of dust encountered in brake maintenance and repair Proc Roy Soc Med 1977 70. 32-37 12 Peto The hygiene standard for chrysotile asbestos Lancet 1978. + 484-89 13 Mancuso TF El Amar AA Carcinogenic risk and duration of employment among ~ asbestos workers In Biological effects of asbestos Proceedings of Dresden International Conference Dresden Anspach 1968 161-66 14 McDonald AD Harper A. El Attar McDonald JC Epidemiology of a primary primary malignant mesothelial tumor in Canada Cancer 1970. 26 914-19 15 Wagner JC Asbestos carcinogenesis Br7 Concer 1975 32 258-59 THE LANCET NOVEMBER 13 1982 The pathological diagnosis of asbestos diseases in people exposed to chrysotile fibre is complicated by the fact that asbestos bodies do not form readily Furthermore in patients with mesothelioma asbestosis may not always be present As in this case analytical electron microscopy may be essential Chrysotile in a biological environment is degraded chemically and physically so that light microscopy is a poor guide to chrysotile exposure The health and safety problem of brake maintenance and repair : " work has been outlined by Morgan In the United States there are about 1.7 million workers in the new and used car business accessory stores and service stations and another 435 000 in repair shops and garages The risk of malignant asbestos disease among these workers seems to be low but mortality data have yet to be thoroughly evaluated With the large numbers at risk more cases may be seen in the future This investigation was supported by a grant from the N.I.E.H.S. ES00928 We thank Dr John H. Evans University of Tennessee for the tissue samples Environmental Sciences Laboratory Laboratory Mount Sinai School of Medicine New York N.Y. 10029 U.S.A. Canadian Tumour Reference Centre Ottawa Civic Hospital Ottawa Canada A. M. LANGER W.T. McCAUGHEY = LR Ae ee T oe mem 8 ae