Document bjNE7G48YV8R9NYmM6JO277y

FILE NAME Brakes BRK DATE 1978 May DOC BRK070 DOCUMENT DESCRIPTION Journal Article - Occupational Exposure to Asbestos and Malignant Mesothelioma in Females - The Lancet * HF LANCET MAY 20 1978 1061 and acter other the 4.15 7 Scan Ninical Cential atauk years urther SSCased w be imary There gro > We Work pread In our ily in ldren thi 180 an resen's year boy who had had clinical features of muscle seakness and scoliosis for at least 5 years before the de- elopment of obvious calf hypertrophy : 3 of the 4 index patients we described cases 1 2 and I were traced as part of a major study of s.M.A. which comprised 102 cases in North England Male cases ! the new syndrome resemble linked Becker muscular Astrophy a more common condition We recognised other cases of this newly identified synfrome within reported case series of S.M.A. Bundey and Lovelace described two brothers with adolescent , IM.A. with calf hypertrophy and other examples are l krown The linked recessive inheritance noted in } uses 3 and 4 of the current series emphasises the need consider this > frome in the differential diagnosis of Becker muscular dystrophy This newly described syn- Some should also be considered when simple male cases M.A. are found within otherwise unaffected families everal examples of linked recessive S..M.A of late d but without hypertrophy | Lown 14.15 The apparent homogeneity of of calves cases with are this also syn- Frome is further evidence for a broadening of differen- tal diagnosis in cases of apparent muscular dystrophy 1 thank Prot I Walton and Prot D A. Shaw for permission to icfrom icfrom case notes of patients who have been under their care Requests for reprints should be addressed to P. Department of Ulkalth Roval Roval ( hildren's hildren's Hospital Brisbane Australia 4029 REFERENCES Pran | H PR thesis University of London 1974 ~~ t 5. Bundev 5. Lovelace R. E. Brain 1975 98 455 3 Procopis P. G. Bale P. in Proceedings 11th World Congress of Neurology 47 Amsterdam 1977 4 Thomas P K. Calne D B Elliott C. F. 7 Neurol Neurosurg Psychiat 1972. 35 208 1 Pearn] H. Carter CO CO Wilson J. Brain 1973 96 463 Pare H. Wason 1 fron Div Chidh 1973.48,425 1973.48,425 PearnJH JH Waison ) reid p 768 car EE Fudson P. Walton IN Bram in the press Bradley 1. Jones 7. Mussini -M Fawcett P. W Muscle Sorte the press achman DBS Murphy SR Nigam P. Hills f R. Brows Neurol Neurol , 1967 16,14 Motumas J. Sica REP.Campbell REP.Campbell REP.CampbelMl. J. Lancet 1971 321 Shan A. M. Anderson M Neurology 1974 477 ~ Pearn } H. Gardner ) Wilson ) neural Ser in the press kumus W. Alter M. Sung 11 Neurology Minneapolis 1968 18 671 Tsukagoshi H. Shon H , Furakawa 1 ibid 1970,20,1188 1970,20,1188 1970,20,1188 s OCCUPATIONAL EXPOSURE TO ASBESTOS AND MALIGNANT MESOTHELIOMA IN FEMALES NICHOLAS J. VIANNA Adele K. PolAN Bureau of Occupational Health and Chronic Disease Research New York State Department of Health Empire State Plaza Tower Building Albany New York 12237 = Summary A study of the occupational histories of 52 females with malignant mesothelioma certain of their relatives carried out to measure the nt this disorder attributable to indirect asbestos posure showed that a signifcantly greater number of abands and fathers of cases than of controls worked i 2 related industries and the relative risk for this factor was 10. The frequency of parental cancer especially gastrointestinal malignancy was also significantly greater for cases than for their controls This raises the possibility of a genetic predisposition to malig- nant mesothelioma Introduction THE occupational hazards of working with asbestos are well established but the hazards of exposure to asbestos in the general environment IS unclear Although there is no convincing evidence that indirect exposure contributes to the occurrence of mesothehomas there have been numerous reports of this rare tumour in individuals exposed at home to dusty clothing or to a source of asbestos air pollution e.g. mines factories in the neighbourhood.-We assessed the possibility that household exposure might be a major risk factor for females with malignant mesotheliomas Methods All female residents of New York State excluding New York City aged 20 years and more who died with histologically confirmed malignant mesothelioma between 1967 and 1977 and were reported to the Bureau of Vital Records of the State Health Department were included in a control study For each patient 1 matched control who died in the same year and of a cause other than cancer was selected from the records of the above Bureau by the following criteria same year age- group at death sex race and county of residence ( where possible the same census subdivision as defined by the US Bureau of Census Washington DC Cases and controls were also matched for marital status at the time ofdiagnosis the information being obtained from their medical records When more than one individual satisfied the criteria a table of ran- dom numbers was used to select a control Field investigators used a set questionnaire to obtain occupational histories for all patients controls and their fathers and husbands up to the time of diagnosis Occupational histories of mothers and sibs of patients and controls were also obtained but not analysed Additional information on exposure was obtained from medical records industrial reports and site visits to the homes of patients and controls Medical personal family and residential histories were also obtained Where possible the homes of patients and controls up to the time of diagnosis were plot- ted on maps which showed the locations of industries using asbestos in New York Classification by social status was by the main occupations of the husbands of patients and controls or of patients themselves if single and graded according to that used for census purposes professionals managerial staff labourers and farm service and private household workers For statistical purposes patients and their matched controls were subdivided according to whether their occupations were asbestos related as defined by Hamilton and Hardy or not The occupations of their fathers and husbands were subdi- vided according to whether exposure was to asbestos or to ,, other pneumoconiosis particles e.g. silica In each instance the frequencies of the two cells which showed dissimilar histories were tested using the binomial p q ... 4 where p equals the probability of success and q the probability of lailure for small frequencies and the McNemar 7 test for 7 large frequencies Results 65 females were reported to have died from malignant mesotheliomas during the year study period but only 52 32 pleural and 20 peritoneal were histologically confirmed The mean age at diagnosis for the confirmed Medical Medical Medical Medical Medical Pa Medical Medical Library Library Library 3 Library TY TY Library Library . . : ah, . 4 _ t . t e fo oq! 4 {- me . a a j i Ps | P . Ws. ibutilns 1062 THE DANC MAEY 20 1971 = CLINICAL DATA OF FIFTEEN FEMALE PATIENTS WHO HAD MALIGNANT MESOTHELIOMA IN NEW YORK STATE EXCLUDING NEW YORK LITY BETWEEN 1967 and 1977 AND THEIR EXPOSURE TO ASBESTOS tas Jilt 1 ; | 1 ' | ' i i 1 Age | Year Site of diag|ndoiasgniossis yr diagnosis mesothelioma i Patient Type of asbestos exposure Occupational Husband Father ' Residential | ber Possible duration * of exposuret before diagnosis vri ( ABC 200 1 1971 | -- Textile worker ABC 200 1974 1 P ; Shoemaker | Shoemaker ; 21 worker ABC 200 - 1974 Pl Textile | | Brake 23 : ' | worker QWHOI S4 1975 : 32773 Textile worker : 2 QWHOI 52 1973 32773 Textile worker . Milliner | QWHOI 67 1974 32773 QWHOI 66 1969 32773 ; -- 40 . 1968 | 32773 Pipe fitter _ ' lining =; i 25 h lining Is : : I +4 , 1973 : Pl | | J 31 1969 | Pl : : | ' K | 51 1 1974 : P | i Lt. 30 1974 j Pl : ' M 75 1975 | 2 : | worker ' ' insulation . company 18 : | worker \ electric . 14 wire worker i Heat insulation | Elevator insula- | | Worker tion worker 1 1 ; Heat insulation | ' 15 . S \ | worker Electric wire Electric wire IS ; N 77 1975 3 I ' | : ' insulation worker cable company ; lining ' i 10 worker ' nor fold 0: 435 435 pat { tou- no Jusi Jusi 1 her tant 25 ME k for hr hr in that 01 52 1 1973 1 Pl , ' Asbestos | 18 for 1 * Peritoneal Pleural welwelll Exposures during different periods were added fifbirbrcc cases was 60-2 years range 22-86 years and all were Caucasian The accompanying table summarises data on the 15 patients who could be said to have had some exposure to asbestos before diagnosis 6 patients A worked in asbestos occupations whereas none of their matched controls had positive histories However there were 2 instances of reverse exposure that is the controls worked with asbestos textiles for 3-7 years but their cases did not 0.1 The median age at diagnosis for patients - was 60-5 years mean 64-8 years 10 patients B. C and N had husbands and fathers who worked in asbestos occupations lived 85 of cases and 73 of controls had lived in the same county for 20 years before death and there was a significant difference between these people and those wh _ had lived for less than 20 years in the same counts ? patients H and M lived within 3.6 km of factore using asbestos in New York State for 20-27 years befor diagnosis Another patient O lived approximately 12 km from an asbestos textile factory for 18 year = Leeds England Interestingly her sister worked in the factory for 5 years and had a pleural mesothelioma = 1973. None of the controls lived within 8 km of asbest factories Patients H and M also had relatives we JON the rela phy part ton hom uns Juri Juri nis high whereas their matched controls did not All these pa- tients routinely laundered their husbands or fathers clothing Patients N were either housewives or were employed as secretaries and clerks in asbesrelated industries In only one instance did the case's husband and father not have positive occupational histories while her matched control's husband worked in the heat insulating industry for 20 years of their married life 0.006 The estimated relative risk of mesothe lioma for this pattern of exposure to asbestos is 10 with a 95 confidence interval of 1.42 to 37-40 If the two instances patients B C where both the patients and their husbands worked in asbestos occupations are excluded the probability 8 or more out of 9 is 0.02 The median age at diagnosis for the 10 patients with this type of exposure was 58.5 years mean 57.8 years 17 patients had fathers and husbands whose occupations were associated with pneumoconioses other than asbestosis but the relatives of their controls were not None of these cases or their matched controls had his- tories of asbestosis or other pneumoconioses For 12 pa- tients the reverse was true relatives of cases not exposed to other forms of pneumoconioses controls exposed 0.05 worked with asbestos There was no difference between subjects and contr in their race religion duration of married life betw death other illnesses requiring hospital admission per sonal histories and socioeconomic status 17 patie had mothers or fathers who had other malignancies bes the parents of their matched controls did not wherea the reverse occurred in 5 pairs i.e. parents of cases no malignancies and those of controls did = XC1 We found no evidence suggesting that affected partes worked in asbestos occupations Gastrointestin malignancies were commonest mothers : intestine 2 intestine 3 The parents of onl controls had similar histories There were no mesothe liomas among the parents of patients or their contr The mean age at diagnosis of patients whose mothen fathers had a history of cancer was 55.9 years meta 53 years This was lower than the mean age for the ' study patients who had no parental history of casos 62.3 years but the difference was not statistically w nificant r test 0.05 Husbands in the two grou0p1 not differ significantly in their cancer histories - 01 _ In 24 instances the spouses of both the patient mt = matched control were interviewed whereas for the ou 28 pairs another degree relative parent 20 hist hist ahi Limo 15 the sate & ofr a -3 my hol J in t get to go wh : g ne. i sorry wey LatiLati Pn LANCET MAY 20 1978 1063 Juration ret before NEVT : \ , , was contacted The two groups of responders did not differ in their answers to the question of asbestos acupations in that both groups gave an equal propor- tion of positive responses Discussion Discussion Discussion Our results suggest that women run the risk of malig- cant mesothelioma not only if they work in asbestos- related industries but also if they are indirectly exposed oc upation to to environmental environmental asbestos . The The husband's occupation factor of was clearly the most important risk factor but 6 of our possibility gains some support from the fact that the mean age at diagnosis of patients with a parental history of cancer was somewhat lower than that for all other study patients Although many questions about the pathophysiology of asbestos disorders remain unresolved it seems clear that simple preventive measures directed at how and where work clothes are laundered might greatly reduce the frequency of malignant mesothelioma Requests for reprints should be addressed to N V. patients also lived in environments where more than one REFERENCEN wurce of exposure was likely The importance of other occupational exposures varies with the types of in- Justry e.g asbestos ' mines and factories * factories shipyards ac , present in an area and their proximity to proximity tomes Residential exposure might be especially impor- tant in large cities whereas in less densely populated York such New areas areas as New excluding excluding New New YYoorrkk CCiittyy this might not be a signincant risk factor gradient exists whether gradient response It is not clear a dose- exists for malignant mesotheliomas Studies of workers in the 1. Sarkort Chure 1. I Hammond oe Biological Effects of Asbestis Timbrell Publication Scientific Scientific no A Timbrell and PO Water .p S 1973 ched by 209 1xon 1973 Bogovski Bogovski ( Vresen 2. 2. 1971,1115 1971,1115 3 Wagner 10 10 Slegs A. Marchand I Br and M. hu 17 200 4 Newhouse MI H Thompson and 196 22. 261 * Lillington A. Tampus W 261 Differding R Nam Nam MJ 1974 Champion 6 Champion P Am Am Rev Rev resp Du Du 1971 , 103 21 21 * McDonald A. D. Harper A. El Attar A. Mellonald ) C Cancer 1970.26,914 1970.26,914 1970.26,914 3 Heller R. M. Janower J. L. Weber L. Am J Roent 1970 108 53 ~ Anderson H A. Das R. Drum M. Eisenben S. Schikott Tun 3 dead der 19h 271 311 industry Quebec milling chrysotile mining and factories manufacturing in and 10 Hammion A. Hardy H. ae Industrial Toxicologyp 421 hu v Acton Massar Harries 13 a factories manufacturing asbestos products suggest 11 If for nccen Hyg 1972. highly exposed that only j only highly groups have an increased risk 12. McEwan FinLayson A. Air A. Gibson A. Br med 1970 for <= J A ] addition for lung and mesotheliomas In addition Whit- 575 , cancer 7. 11 244 13 enveenvr er Res 1976 well et al.16 found that dried lung tissue of patients who 14 McDonald in Biological AsbesAstbeo sts os PARC PARC Scientific Publis J of hed of this disorder contained over 000 asbestos N by ( Unison Timber te and 1 Wagner edited BogovskBogoivski V findings ^bres ^bres gram But indirect per exposure j our findings indirect on Wagner p 15 Newhouse I Exon Jp 203 dir " . . 10 ) support and those of other occupational studies13.17 studies13.17 studies13.17 19 support other occupational studies13.17 the suggestion that the incidence of mesothelioma is not related simplysimply to the magnitude of dust exposure The M In White H. Scurt 1. Grunshaw Flea 1977. 321,3 17 jores S. P. Pooley D. Smith G R.C Term 1976 52 117 WJ 18 Nicholson WJ Ann NY Acad Sci 1976,271 1976,271 152 Melkmaldke McDonald 19 Melkmaldake Melkmaldake Melkmaldake M. , GW McDonald A Rinsiter Baty . : actories physical properties of certain types of asbestos might partially alter the actual dose of asbestos to which a per- of " Archisoner Archisoner Hith 1972 hi 2i8n 20 Timbrell Biological Efects Efects Asbestos FARC FARC Scientific Publication no edited Bogovski FC A Cafson Timbrell 10 \\ > before tely 12 cars cars in in this iuma in isbestos mesothe son is exposed For example the incidence of homa in people who work with chrysoule asbestos is than that to considerably lower those exposed crocido- lite or amosite possibly because chrysotile libres are f curly and more readily arrested in the upper respiratory tract Pulverisation of chrysotile fibres does produce a 8 v A 1972.5.279 21 Timbred Rendall 1 Gn Podchor Podchor Podchor 1972.5.279 22. Riley L. O'Grady in p 92 York 1961 R. R. Airborne infection New 23 Gross P. de reville R. P. Tolker B Kaschak M. Babyak M Archs entir Hith 1967 343 24 Lynch K M. Melver A. Cain J. R. Archs ind Hich 1957. 15. 207 25 Ree4v9 es6A. L. Puro H. E. Smith G. Vorwald A. J. Envir Res 1971 es who { higher incidence of mesotheliomas in animal experiments Industrial operations which enhance the proba- | Controis bility of entry to the periphery of the lung such as those before which promote aerosol formation might be another ~ in perDatients ies but whereas ses had 0.008 parents testinal ach 2 . only 2 Resothe introls hers or median modifying factor which influences the pathological response to asbestos Unlike most forms ofdust particles the size of droplet nucler settle very slowly and most are carried along in the inhaled air Insulation workers appear to have a higher risk of mesothelioma than factory workers making asbestos products This might be Jue to the aerosol effect which can occur when insulat- powders mixed with fathers Interestingly cement powders are 1 our patients had husbands and fathers employed employed in the insulating industry In contrast the high fre- quency of asbestosis in textile workers might be related to the high droplet index volume setting count which occurs when spun fibre is woven into asbestos fabric CLOSTRIDIUM DIFFICILE AND THE ^ ETIOLOGYOF PSEUDOMEMBRANOUS COLITIS H. E. LARSON P. HONOUR A. B. PRICE Clinical Research Centre and Northwick Park Hospital Watford Road Harrow Middlesex HAI 3UJ S. P. BORRIELLO Bacterial Metabolism Research Laboratories Public Health Laboratory Serence Colindale London NW9 SHT The 35 Cancer lly The unusually high frequency of cancer among the , parents of mesothelioma patients is difficult to interpret ( I could merely indicate that mesothelioma patients Summary screened for Bacterial isolates from 5 patients with pseudomembranous colitis P.M.C. were toxin production Strains of Clostridium up. come from cancer families Experimental studies from 4 patients produced in vitro a toxin similar to that ! suggest that the histological response to asbestos varies found in P.M.c. facal suspension These were identified ' it and with different animal species and in man genetic as C. difficile Use of strains from 2 patients induced . Other factors might alter susceptibility to mesothelioma This a fatal enterocolitis when inoculated orally into hams- aN '