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FILE NAME Household Contact HC DATE 1978 May DOC HC024 DOCUMENT DESCRIPTION Journal Article - Occpational Exposure to Asbestos and Malignant Mesothelioma in Females *- THE BOSTON MASS AND LONDON . SATURDAY 20 MAY 1978 VOL I FOR 1 , sot, = ~ of aspirin : to the depends eer r dosage sease and dometh- 1 food or ossibility of dosage and rescribing Y Cimetidine Bramstem ORIGINAL ARTICLES Cell Degeneration and Gross Calf Hypertrophy ; p Anterior Onset dexamethasone interaction Adolescent Hudgson f.r.A.C.P. GEORGE WASHINGton University occupatoicupaotionanl aocclupational Exposure HudgsonAsbestos adMELFARB LIBRAS Cnical Problem addMELFARB HEALTH SCIENCES LIBRAS Or in Females 2300 EYE STREET N. W.1061 Mesothelioma Mesothelioma MesotheliomaM.D. Adele Polan M.a. Vianna WASHINGTON N. Colitis Clostridium difficile and the Aetiology of Pseudomembranous Larson M.D. A. B. Price M.R.C.PATH P. Honour 1978 MAY MAY 30 30 B.Sc. D. C. 20037 1063 H. Borriello Cromoglycate Vaz Cromoglycate G.A. Drag Weitzman A V.A. Koivisto Skin Cromoglycate in Treatment of Adverse Reactions to Foods L. K Tan m.D. Prof. J. W. Gerrard F.R.C.P.C. Immunological Neutropenia M.D. T. P. Stossel M.D. Mary Desmond Preparation Necessery Before Insulin Injection M.D. Prof. Philip Felig M.D. 1066 1068 1072 Dysfunction DFW J.K Cumming > B. Foster Phenytoin Phenytoin interaction Wilma Jack Two Clinical Syndromes and Mianserin Or A. E. Tulloch Carbamazepine and Bradycardia Dr Louis Herzberg Aunniography and the False positive Amniotic A.F.P. Dr Aubrey Milunsky Dr R. K. Neff Ultrasound in Pregnancy Prof. Stuart Campbell and others transfusion Before and During Transplant Surgery Dr H. Bryngur and others estrogen and Climacteric Symptoms Dr T. Cuan PRELIMINARY COMMUNICATION Acid Hydrolases in Monocytes -3 Bowel Disease Chronic Disease Arthritis Rheumatoid Arthritis N. Ganguly M.D. G. Kingham M.R.C.P. B. Lloyd I.M.L.S. C. Lloyd F.L.M.L.S. Price P. 5.PHIL , Ralph Wright D. R. Triger Prof. , M.R.C.P. F.R.C.P. 1073 1073 in Community Psychiatry Depolarised Pseudomembranous Colitis The Newborn in Hospital Faculty of Occupational Medicine When is a Contract Ajas LETTERS TO THE EDITOR 1079 1080 1081 1081 1082 Dermal Dr J. K. Exposure to Paraquat Howard hormone Profile Dr T. S. Beer and others Motilin and Carcinoid Tumour Dr F. Sundler and others Adjuvant chemotherapy in Operable Breast Cancer Mr R. Wilson F.R.C.S.E others Early Diagnosis of Duchenne Muscular Dystrophy Gardner Dystrophy Dr and thers Caloramphenicol Poeumoco in West Africa Dr David Hansman The Antitrypsin Phenotype MZ in Acute Anterior Uveitis Dr D A. Brewerton and others Nauces Nauces Books 1 OCCASIONAL SURVEY Pregnancy Cancer DoesAgainst Ovarian ? Cancer Against Beral M.R.C.P. Patricia Fraser M.D. Car Chilvers M.SC. PREVENTIVEMEDICINE Cigarette Consumption and > Deaths from Coronary disease Christopher Bain M.D. CH CH Hennekens M.D. Bernard Rosner PH.D. FE FE Speizer M.D. Prof Mary Jane Jesse M.D. , WESTMINSTER WESTMINSTER COMMENTARY FROM | The Review Review Body's Body's Report { { ' OBITUARY Richard Sydney Allison _ 1075 1083 1087 1107 1108 Home Hospital or for Myocardial Infarction Dr. M. Oliver Dr R. N. gle Kenneth Shearer Dr. D. W. Barritt and others Dural Dural PaiPnainNorTIS Mr H. Murley F.R.C 1089 1090 Mr Mr Selwyn Norman Crawfor, d f.r G.S.E. G.S.E. G.S.E. G.S.E. Cimetidine and Malignant Gastric Ulcers Dr C. Murray and others 11009922 Hand mirror Dr G. Minoli and othersBenign Cells Benign or 1092 Captain H. R. Schumacher and others Transluminal Dilatation for Coronary Stenosis 1093 Dr Edward Murphy Prof. S. H. Rahimtoola Dr A. Gr^...ntzig Bacteriuria of Cove Cor vet rt Bacteriuria in Prof.Schoolgirls Arneil Superoxide dismutase Deficiency in Rheumatoid Arthritis Cough and Dr M. Impaired others receptor FuncFtuincotnionin Malik Leprosy Dr S. K. and others Thrombocytopenia Plasmapheresis on Thrombocytopenia 1093 1094 1094 1095 Dr Takashi Gandolfo M. Gandolfo andothoertshers Gastritis Cimetidine a Possible Explanation Explanation Dr P. E. Nicholls 1095 Dr Krisun Henry Ayl Hydrocarbon Hydroxylase and Bronchogenic Carcinomas Carcinomas Associate with Smoking Dr Rolf Korsgaard Dr Enk Trell Tissue Penetration by Cepaalosporins Dr Sydney Seiwvn Dr Richard W'ise Dr. A. Gillett Mucocutaneous Reactions during Mycoplesme Mycoplesme Dr pneumonia F. Swift Infection Dr W. Stevens Serratia marcescens Colomising the Gut S. Jones and others Measurement of Lactoferrin in juice Pancreatic Dr C. Figarella and others General Anesthesia for High Total Irradiation Prof. Peter Jacoos Dr Helen King Trimethylamine Metabolism iz Liver Discase Dr Robin Marks and other NOTES AND NEWS Cancer of the Pancreas the World Scene Fecollections of Medical Schools adrenoceptor Blocking Agents Food University of London University of Edinburgh University of Surrey University of Glasgow Medical Art Society Eubional Eubional 1 Office 7 Adam Street London WC2N 6AD England North Edition published weekly by Little Brown and Company subcRreiapctoinoSnecond mailing ... 400 St. Boston Mass 02106. In U.S. and Canada annual subcription 30 00 resident and intern rate 21.50 single copy class postage paid at Boston Mass and at additional wee mS TP ee 1070 additional LANCET MAY 20 1978 myopathic over the yeyear ar intervalinterval to secondary rised in table and idrome are caused charcter those clinical onset for other is 4 months 9-18 forms and 38 years -onset form years differential a helpful A. genes tend to cause the age of 8-9 years s point awaits further PATIENTS WITH S.M.A. SET Walking unaided Nofi Yes Yes Yes Yes ears Latest age able to run YT net . 16 13 16 15 20-23 LT , cur in muscle diseases uscle groups may be change in primary ented and there -ue cause of the gross en in such cases We | ion of genuine work res and widespread zment fig 2 In our ophy is seen only in id is rare in children hildhood s.m.A. this in only one case an 1. Relatively late presenta kness . family who is normal Rela ypertrophy initially unger brother has a wad a THE THE LANCET MAY 20 1978 10 old boy who had had clinical features of muscle 11weakness and scoliosis for at least 5 years before the de- velopment of obvious calf hypertrophy velopment3 the 4 index patients we described cases , 2 and were traced as part of a major study of s.m.A. which comprised comprised 102 cases in North England Male cases new syndrome resemble linked Becker muscular dycstroopmhyprised dystrophy a more common condition We recognised other cases of this newly identified syndrome within reported case series of S.M.A. Bundey and Lovelace described two brothers with adolescent SM.A. with calf hypertrophy and other examples are SM.A.known The linked recessive inheritance noted in cases 3 and 4 of the current series emphasises the need consider this syndrome in the differential diagnosis of Becker muscular dystrophy This newly described syn- frome should also be considered when simple male cases S.M.A. are found within otherwise unaffected families Several examples of linked recessive S.M.A. of late , but without hypertrophy of calves are also 14.15 known The apparent homogeneity of cases with this syndrome is further evidence for a broadening of differenial diagnosis in cases of apparent muscular dystrophy We thank Prof. J. Walton and Prot D. A. Shaw for permission to quote from case notes of patients who have been under their care Requests for reprints should be addressed to J. P. Department of Child Health Royal Children's Hospital Brisbane Australia 4029 REFERENCES 1. Peara J. H. PH.D. thesis University of London 1974 1. Bundey S. Lovelace R. E. Bran 1975 98 455 1977 1. Procopis P. G. Bale Proceedings 11th World Congress of Neurology p.47 Amsterdam 1977 + Thomas P. K. Calne D. B. Elliott C. Neurol Neurosurg Psychiat 1972. 35 208 PearnJ. H. CarterC. O. Wilson J. Bram 1973 96 463 Pearn J. H. Wilson J. Archs Dis Childh 1973 48 425 * PearnJ. H. Wilson J. ibid p.768 the press 1. Pearn J. H. Hudgson l Walton N. Brain in Bradley W G. Jones M. Z. Mumum J.-M. Fawcett P. R. W. Muscle Nerve 1in the press 10 Drachman ) B. Murphy S. R. Nigam M. P. Hilis J. R. Archs Neurol 1967 16 14 11 McComas A. J. Sica R. E. P. Campbell M. J. Lancet 1971 i 321 M. Neurology 12. Achan A. M. Anderson 1974 24 477 11 Pearn J. H. Gardner D. Wilson J. J. neurol Sci in the press 14 Kennedy W. .. Alter M. Sung J. H. Neurology Minneapolis 1968. 18 671 19 Tikagoshi H. Shoji H. Furakawa T. ibid 1970 20 1188 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 and certain of their relatives carried out to measure the nsk of this disorder attributable to indirect asbestos exposure showed that a significantly greater number of busbands and fathers of cases than of controls worked in related industries and the relative risk for this factor was 10. The frequency of parental cancer e pecially gastrointestinal malignancy was also signi cantly greater for cases than for their controls Th raises the possibility of a genetic predisposition to mali nant mesothelioma Introduction THE occupational hazards of working with asbesti are well established but the hazards of exposure i asbestos in the general environment is unclear Although there is no convincing evidence that indirec ~ exposure contributes to the occurrence of mesothe liomas there have been numerous reports of this rar - tumour in individuals exposed at home to dusty clothin or to a source of asbestos air pollution e.g. mines fac tories in the neighbourhood.-We assessed the possib lity that household exposure might be a major risk fa tor for females with malignant mesotheliomas Methods All female residents of New York State excluding New Yor City aged 20 years and more who died with histologicall confirmed malignant mesothelioma between 1967 and 197 and were reported to the Bureau of Vital Records of the Stat Health Department were included in a control study Fc each patient 1 matched control who died in the same year an of a cause other than cancer was selected from the records ( the above Bureau by the following criteria same year ag group at death sex race and county of residence where po sible the same census subdivision as defined by the U.S. Bi reau of Census Washington D.C. Cases and controls wer also matched for marital status at the time of diagnosis the ir formation being obtained from their medical records Whe more than one individual satisfied the criteria a table of ran investigator dom numbers was used to select a control Field used a set questionnaire to obtain occupational histories for al patients controls and their fathers and husbands up to the ume of diagnosis Occupational histories of mothers and sib- analysed of patients and controls were also obta.ned but not Additional information on exposure was obtained from medi cal records industrial reports and site visits to the home of patients and controls Medical personal family and resi dential histories were also obtained Where possible the home of patients and controis up to the ume of diagnosis were plotted 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 manageria 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,,o"r not The occupations of their fathers and busbands were subdivided 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 = = where p equals the probability of success and q the probability of failure for small frequencies and the McNemar o test for 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 LYOURLIN LYOURLIN UNIVEDCITYUNIVEDCITY LYOURLINUNIVEDCITY VATNINYCHIL eanue GS0ERbOnmwieUINGTOVANIYCHL IQYNZNaconerWAT WATT aconer 1062 THE LANCET , MAY 20 193 CITY EXCLUDING CLINICAL DATA OF FIFTEEN FEMALE PATIENTS WHO HAD MALIGNANT MESOTHELIOMA IN NEW YORK STATE Between 1967 and 1977 and their exPOSURE TO ASBESTOS NEW { YORK Type of asbestos exposure a | Age Year Site of | | Patient diagnosis diagnosis mesothelioma Pauent Occupational Husband Father ABC 300 1971 P Textile worker ABC Pl | ABC 300 1974 Pl Shoemaker Shoemaker 79 1974 Texule worker Brake worker i EP2EE ANLUI 54 1975 Textile worker ANLUI 8293 1973 EP2EE Textile worker Milliner ANLUI 8293 1974 EP2EE bose | 1969 EP2EE ANLUI 8293 Pipe fitter 8293 EP2EE Brake ANLUI 1968 worker I I 1973 Pl Heat insulation worker j 31 1969 Pl K 51 1974 P L 30 1974 Pl M KF2 1975 E electric wire worker Heat insulation | Elevator insula- worker uon worker Heat insulation worker Electric wire insulation worker N KF2 1975 E 0 52 1973 E lining worker * Pentoneal Pleural Exposures during different periods were added Residential ofPossibledur expdioasgunornestbes yr 122 , 122 23 2 25 Brake 15 company te 14 15 Electnc wire cable company , Asbestos factory $ IS 10 18 ~ cases was 60 years range 22 8y6ears 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 y7ears but their cases did not 0.1 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 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 years 17 patients had fathers husbands whose occu- pations 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 85 of cases and 73 of controls had livien tdhe same county for 20 years before death and there was significant difference between these people and thoswies had lived for less than 20 years in the same county1 patients H and M lived within 3-6 km of factora using asbestos in New York State for 20 2y7ears befor diagnosis Another patient 0 lived approximately 1-2 km from an asbestos textile factory for 18 yean a Leeds England Interestingly her sister worked in the factory for 5 years and had a pleural a mesothelioma 1973. None of the controls lived within 8 km of asbena factories Patients H and M also had relatives wis worked with asbestos There was no difference between subjects and contros in their race religion duration of married life befort per death other illnesses requiring hospital admission sonal histories and socioeconomic status 17 patiem bu had mothers or fathers who had other malignancies the parents of their matched controls did not wheres bad the reverse occurred in 5 pairs i.e. parents of cases no malignancies and those of controis did 0.008 We found no evidence suggesting that affected parem worked in asbestos occupations Gastrointesung mothers stomach malignancies were commonest ! intestine 2 intestine ) The parents of och! controls had similar histories There were no liomas among the parents of patients or their a The mean age at diagnosis of patients whose mother meda of fathers had a history of cancer was 55.9 years 53 years This was lower than the mean age for study patients who had no parental history core statistically 62.3 years but the difference was not uk patient nificant & test > 05 Husbands in the two 0 = not differ significantly in their cancer histories In 24 instances the spouses of both the othe matched control were interviewed whereas for st 28 pairs another degree relative parent 15 10 18 had lived in the . and there was no le and those who same county 2 km of factories 2y7ears before proximately 1-2 for 18 years in - worked in this nesothelioma in 3 km of asbestos i relatives who cts and controls _ ried life before admission per.us 17 patients alignancies but lid not whereas nts of cases had affected parents Gastrointestinal stomach 2 arents of only 2 tre no mesothe r their controls hose mothers or 9 years median a age for the 35 story of cancer statistically sig- did ! two groups stories 0.1 he patient and ~ asfor the other parent or sib LANCETLANCET MAY 20 1978 THE LANCET contacted The two groups of responders did not their answers to the question of asbestos their affer aupations in that both groups gave an equal propor- aupations responses | 000 positive Discussion Discussion results suggest that women run the risk of malig- mesothelioma not only if they work in asbestos- sant mesothelioma but also if they are indirectly exposed industries related asbestos The husband's occupation environmental 20 important the most risk factor but 6 of our clearly 525 also lived in environments where more than one cleary patents importance other patents of exposure was likely The of exposures varies with the types of in- occupational e.g. asbestos mines and factories shipyards Justry present in an area and their proximity to 11-139 Residential exposure might be especially impor- somes populated in in large cities whereas less densely ant in New York excluding New York City this such as not be a significant risk factor ughtis not clear whether a response gradient exists ught mesotheliomas Studies of workers in the arysoule malignant mining and milling industry in Quebec and arysoule factories manufacturing asbestos products's suggest at only highly exposed groups have an increased risk mesotheliomas addition for lung cancer and In Whit- well et al found that dried lung tissue of patients who hed of this disorder contained over 000 asbestos ^...bres per gram But our findings on indirect exposure and those of other occupational studies support the suggestion that the incidence of mesothelioma is not related simply to the magnitude of dust exposure The physical properties of certain types of asbestos might parually alter the actual dose of asbestos to which a perxon is exposed For example the incidence of mesothe- jama in people who work with chrysotile asbestos is considerably lower than that in those exposed to crocido- sie or amosite possibly because chrysotile fibres are curly and more readily arrested in the upper respiratory tract Pulverisation of chrysotile fibres does produce a sigher incidence of mesotheliomas in animal experi- ments Industrial operations which enhance the proba- sility of entry to the periphery of the lung such as those which promote aerosol formation might be another modifying factor which influences the pathological response to asbestos Unlike most forms of dust particles the size of droplet nuclei settle very slowly and most are amed along in the inhaled air Insulation workers appear to have a higher risk of mesothelioma than fac- tory workers making asbestos products This might be jue to the aerosol effect which can occur when insulat- ing cement powders are mixed with water Interestingly of our patients had husbands and fathers employed the insulating industry In contrast the high frequency of asbestosis in textile workers might be related a the high droplet index volume setting Count which occurs when spun fibre is woven into asbestos fabric The unusually high frequency of cancer among the parents of mesothelioma patients is difficult to interpret It could merely indicate that mesothelioma patients from cancer families Experimental studies suggest that the histological response to asbestos varies different animal species and in man genetic factorfs actors might alter susceptibility to mesothelioma This 1063 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. J. V. REFERENCES 7 1. Selikoff.. Churg J. Hammond Hamond E. C. in Biological Effects vi Asbestin A.R.C. Scientific Publication no 8. edited by ~ Bogovski J. C. Crilson V. Timbrell and C. Wagner p 209. Lyon 1973 E. Lamet 1973 3. Wagner J. C. bleggs C. A. Marchand P. Br J. md Med 1960 17 260 4. Newhouse M. hompson H. ibid 1968 22 261 5. Lallington ( A. Jamplis W Differding J. R. New bagi J Med 1974 291 583 6. Champion P. Am Rev.resp Rev.resp Du 1971 103 821 7. McDonald A. D. Harper A. El Attar O. A. McDonald J. C. Cancer 1970 26,914 26,914 8. Heller R. M. Janower J. L. Weber A. L. Am J. Roent 1970 108 53 9. Anderson H. Lilis R. Daum S. M. Fischbein A. S. Selikorf 1. J. Ann NY Acad Sen. 1976. 271 311 10. Hamilton A. Hardy H. L. in Industrial Toxicology p 421. Aci^nMassar chusetts 1974 11 Harries 1 G. Ann occup Hyg . 1972. 135 McEwan 12. J. Finlayson A. Air A. Gibson A. A. M. Br med J. 1970 iv 13. Edge J. J. enter Res 1976 11 244 14. McDonald j C. in Biological Effects of Asbestos Scientific 1.A.R.C. Scientific l'ublica- tion no 8 edited by 1. Hogovski J. C. Gilson V. Timbrell and j C. , Wagner p ^ 1.von 1973 15. house M. L. ibid p 203 16. Whitwell F. Semi | Grimshaw M. Thorax 1977 321 377 17. Jones J. 5. P. Pooley F. D. South P. G. LAR.C. Inserm 1976 52 117 18. Nicholson W. J. Ann N.Y. Acad Sci 1976 271 152 19 Mulkonald J. C. Beckiake M. R. Gibbs G. W. McDonald A. D. Rinsiter C. Archis entir Hith 1972 28 61 20 Timbrell : Biological Effects of Asbestos J.A.R.C. Scientific Publication no ^ edited by P. Hogovski C. Gilson V. Timbreli and L. Wagner Wagner 295.1.sun 295.1.sun 1973 21 Limbrell V. Rendall G. Poteder Technol 1972 5 279 F. 22. Raley R. L. O'Grady an Airborne Infection p 92. New York 1961 23. Gross P. de Trevile R. T. P. Tolker E. B. Kaschak M. Babyak M. A. Archs enter Hich 1967 15 343 24. Lynch K. M. Melver F A. Cain J. R. Areks ind Hith 1957. 15 207 25. Reeves A. L. Puro H. E. Smith R. G. Vorwald A. J. Encer Res 1971 4.496 CLOSTRIDIUM DIFFICILE AND THE ^ TIOLOGYOF PSEUDOMEMBRANOUS COLITIS H. E. LARSON P. HONOUR A. B. PRICE Clinical Research Centre and Northwick Park Hospital Watford Road Harrow Middlesex HA1 3UJ S. P. BORRIELLO Bacterial Metabolism Research Laboratories Public Health Laboratory Service Colindale London NW9 NW9 SHT Summary Bacterial isolates from 5 patients with pseudomembranous colitis P.M.C. were screened for toxin production Strains of Clostridium from 4 patients produced in vitro a toxin similar to that found in P.M.C. f^calsuspension These were identified as C. difficile Use of the strains from 2 patients induced a fatal enterocolitis when inoculated orally into hams- pe eoate THE LANCET MSY 20 1978 - READER FILE R. A. LEMEN 1061 year boy who had had clinical features of muscle weakness and scoliosis for at least years before the development of obvious obvious calf hypertrophy 3 of the 4 index patients we described cases 1 2 and 3 were truced as part of a major study of 5.M.A. which comprised 102 cases in North England Male cases of the new syndrome resenible linked Becker muscular dystrophy a more common condition We recognised other cases of this newly identified syndrome within reported case series of S.Ma. Bundey and Lovelace described two brothers with adolescent s.st.a. with calf hypertrophy and other examples are known The linked recessive inheritance noted in 3 cases and 4 of the current series emphasises the need to consider this syndrome in the differential diagnosis of Becker muscular dystrophy This newly described syndrome should also be considered when simple male cases of ... are found within otherwise unaffected families Several examples of linked recessive s.m.a. of late this factor was 10. The frequency of parental cancer especially gastrointestinal malignancy was also significantly greater for cases than for their control This This raises the possibility of a genetic predisposition to malig- nant mesothelioma mesothelioma Introductioa 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 mesothe liumas there have been numerous reports of this rare tumour in individuals exposed at home to dusty cloclung or to a source of asbestos air poilution e.g. mines facdries in the neighbourhood We assessed the possibility that household exposure might be a major risk factor for females with malignant mesotheliomas onset but without hypertrophy of calves are also known.14.k1nown.14.1 Alethods The apparent homogeneity of cases with this syndrome is further evidence for a broadening of differential diagnoses in cases of apparent muscular dystrophy We thank Prof. } Walton and Prot 1 A. Shaw for permission to quote from case nutes of patients who have been under their care Requests for reprints should be addressed in J. P. Department of Child Health Ku at Children's Children's Hospital Heisbane Austesha 4029 REFERENCES 1. Pearn J. H. ri.a. theis University of London 1971 2. Bundes S. Lovelace R. E. ++ 1971 98 431 3. Procopia G. Ha Pin Pin Proceedings 17th World Congreosf tNeurology Neurology p.47 fsterdam .977 + Thomas P. K. Cane O. B. Ellis C. 7 New 21. Haurosurg Piyekut 1272 35.71 1. PearnJ H. Care O dum] % de. ack. b a [ f Wis Speke Qi Chun 19710970.4.9 - 42 9 7 Pearn.; H ilsonHartm 2 ** 1 Vesra.Bradley Hartm Hartm & Brain the 01S 9. Bradley W. G. Jane M. Mussim ... Fawant P. W. Muscle Never the press 10. Drachman K Murphy S. R. Nigam M. Hills J. R. Arcko Neural 1967 16 14 1971 11. MeComau A. .. Siz R. P. Campbel M. Lanzer 1.321 12. Achan AL..Anderson M Nesrawer 19744 77 A GALa.r.dAnndeerrsoMn edwinNesrawer 24 13. l'earn J. H D. Wilson J. } neurot Sex at the permal 14. Kennejr W. K. Alter M. Song J. F. Newswirer Ironcsputes 1968 18 671 15. Trukagushu H. Shan H. Furakawa T. ibid 1970.20 1970.20 1168 OCCUPATIONAL EXPOSURE TO ASBESTOS AND MALIGNANT MESOTHELIOMIAN FEMALES 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 cantrol study ^ or 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 sarme year age- group at death sex race and county of residence where pos- sible the same census subdivision as defined by the U.S. Bureau of Census Washington D.C. Cases and controls were diagnosis also matched for mantal status at the ume of formation obtained the in- being from their medical records When more than one individuai satisfied the criteria a table of ram dom numbers was used to select a control Field investigators used a set querusedure to obtain occupational histories for all patients controls and their fathers and husbands up to the ume of diagnosia Occupauenal histories of mothers and sibs of patients and controls were also obtained but not antalysed Additional information on exposure was obtained from medi- cal records industrial reports and site visits to the hames of patients and controls Medical personal faonly and residential histories were also obtained Where possible the homes of patients and controls up to the time of diagnosis were plot- ted maps showed of on which the locatioindunstrsies using by asbestos in New York Classification by social status was the maia occupations of the husbands of patients and controls or patients and graded procesionais to that used for themselves census themselves if purposes single processionais according managentai staff labourers and fards service and private house- hold workers For stanstical 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- ~ Nicholas J. VIANNA ADELS K. POLAN Bureau of Occupational Health and Chronic Disease vided according to whether exposure was in asbestos or to other pneumoconiosis inducing particles e.g. niiinceaa ch instance the frequencies of the two cells which showed distram- Research New York State Department of Health Empire l^/r histories were tested using the binomal p q whate State Plaza Tower Building Albany New York 12237 p equals the probability of success and q the probability of failure for small feequencies and the Me^ ommar17 tess for Summary A mudy of the occupational historics of farge frequencies . 52 females with malignant mesothelionia and certain of their relatives carried out in measure the Results ee risk of this disorder attributable to indirect asbestos 65 females were reported to have died oe from malignant exposure showed that a significantly greater number of mesotheliomas during the 11 year study period but only e husbands and fathers of cases than of controls worked 52 32 pleural and 20 peritoneal were histologically in asbestos industries and the relative risk for confirmed The inean age at diagnosis for the confirmed ee Se RT 0 " a)23 * a i) aad 4,5 > rtd a Hi od ay wa? ee wee eee ei en ee ye be aweey : te yee A tg EB . iene: RA noreewn Ieee oamee ona xe vfrerg ee fr rita me, - ws hed as eet nate SehrDota meng CoB LAS Nery F-4 ean a ne RNs'wots, 3 rd Mire sege eredeo: are . v zy 7 ww 1062 THE LANGET MAY 20 1976 CLINICAL DATA OF FIFTEEN FIFTEEN FEMALE PATIENTS WHO HAD MALIGNANT MESOTHELIOMA IN NEW BETWEEN 1967 and 1977 and THEIR EXPOSI RE TO ASBESYTOOS RASBKESTOSSTATE EXCLUDING NEW YORK CITY Type of asbestos exposure Age at Year Patient | diagnosis yr diagnosis > 238 1971 C1 238 1974 C1 79 1974 DEFGH 8293X 1975 DEFGH 8293X 1973 DEFGH 8293X 1974 DEFGH 8293X 1969 DEFGH 8293X 1963 i 44 1973 + 31 1969 K Hos 1974 L 30 1974 M 7 1975 N 77 1975 0 2 1973 Site of mesothelioma 45C 45C 45C 33773 33773 33773 33773 33773 E Pp P P Pl R Patar Husband Father Textile work Shumake Shoemaker Textile worker | Brake gQtrtce ~~ Textile worker Textile worker Milliner Pipe fimer Brake - worker Hess insubs worker electr WITH SKET Healt Healt | WORKER Heat an Elevator insula Iran worker worker Electric wire insulation worker Brake- Peritoneal Cleural + Exposures during different perinds were added Residential Lining Brake company . . Elorrere itera, cable company Asbestos factory af exposuret before dragnosis je S 11 23 N 2 33 33 33 18 14 43 3 11 10 18 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 come exposure to asbestos before diagnosis 6 paumis A worked in asbestos occupations whereas none of However their matched controis had positive histones there were 2 instances of reverse exposure that is the controls worked with asbestos textiles for 3 y7ears but their cases did not 0-1 The median age at diagnosis for patients A was 60 years mean 64-8 years 10 patients B C and N had husbands and fathers who worked in asbestos occupations whereas their matched controls did not All these pa- tients routinely laundered their husbands or fathers clothing Patients G were either housewives ar were employed as secretaries and clerks in asbes- related industries ^ nonly one instance did the case's husband and father not have positive occupational histories while her matched control's husband worked in the beat 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 worked'in asbestos occupations are excluded the probability 8 ar more out of 9 is 0-02 The median age at diagnosis for the 10 parients with this type of exposure was 58.5 years mean 57-8 years years 17 patients had fathers and husbands whose occu- pations were associated with pneumoconioses other than asbestosis but the relatives of their controls were not None of these cases or their matched controls had histories of asbestosis or other pneumoconioses For 12 patients the reverse was true retarives of cases not exposed to other forms of pneumoconioses controls exposed 0.05 % of cases and 73 of controls had lived in the same county for 20 years before death and there was no sigu^-cantdifference between these people and those who had lived for less than 20 years in the same county 2 patients H and M lived within 3-6 km of factories using asbestos in New York State for 20 2y7ears before approximately diagnosis Another patient 0 lived approximately 1-2 km from an asbestos textile factory for 18 years in Leeds England Interestingly her sister worked in this factory for 5 years and had a pleural mesothelioma in 1973. None of the controis lived within 8 km of asbestos factories Patients H and Mt also had relatives who worked with asbestos controls There was no difference between subjects and in their race religion duration of married lite before death other illnesses requiring hospital admission personal histories and socioeconomic status 17 patients had mothers or fathers who had other malignancies but the parents of their matched controls did not whereas the reverse occurred in 5 pairs i.c. parents of cases had no malignancies and those of controls did 0.003 We found no evidence suggesting that affected parents worked in asbestos occupations Gastrointestinal malignancies were commonest stomach 2 intestine 2 intestine 3 The parents of only 2 controls had similar histories There were no mesothe- liomas among the parents of patients or their controls The mean age at diagnosis of patients whose mothers or fathers had a history of cancer was 55-9 years median 53 years This was lower than the mean age for the 35 study patients who had no parental history of cancer 62-3 years but the difference was not statistically sigmficant test 0-05 Husbands in the two groups did not differ significantly in their cancer histories 0-1 In 24 instances the spouses of both the patient and menched control were interviewed whereas for the other 28 paars another degree relative parent or sibi we aeons THE LANCET MAY 20 1978 1063 was contacted The two groups of responders did not diferin their answers to the question of asbestos occupations in that both groups gave an equal proporuon of positive responses Discussion Our results suggest that women run the risk of malignant mesothelioma not only if they work in asbestosrelated industries but also if they are indirectly exposed to environmental asbestos The husband's occupation was clearly the most important risk factor but 6 of our patients also lived in environments where more than one source of exposure was likely The importance of other occupational exposures varies with the types of industry e.g. asbestos mines and factories shipyards etc. present in an area and their proximity to homes Residential exposure might be especially important in large cities whereas in less densely populated areas such as New York excluding New York City this might not be a significant risk factor It is not clear whether a response gradient exISTS for malignant mesotheliomas Studies of workers in the chrysotile mining and milling industry in Quebec and in factories manufacturing asbestos products suggest that only highly exposed groups have an increased risk for lung cancer and mesotheliumas In addition Whitwell et al found that dried lung tissue of patients who died of this disorder contained over 100 000 asbestos fibres per gram But our findings on indirect exposure exposure and those of other occupational studies ** support the suggestion that the incidence of mesothelioma is not related simply to the magnitude of dust exposure The physical properties of certain types of asbestos might partially alter the actual dose of asbestos to which a per503 is exposed For example the incidence of mesothe loma in people who work with chrysotie chrysotie asbestos is considerably lower than that in these exposed to crocidelite or amosite possibly because chrysoure fibres are curly and more readily arrested in the upper respiratory tract Pulverisation of chrysotile fibres does produce a higher incidence of mesotheliomas in animal expenments Industrial operations which enhance the proba- bility of entry to the periphery of the lung such as those which promote aerosol formation might be another modifying factor which influences the pathological response to asbestos Unlike must forms of dust particles the size of dropiet nuclei settle very slowly and most are carried along in the inhaled air Insulation workers appear to have a higher risk of mesothelioma than faetory workers making asbestos products This might be due to the aerosol effect which can occur when insulat- ing cement powders are mixed with water Interestingly 5 of our patients had husbands fathers 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 The unusually high trequency of cancer among the parents of mesothelioma patients is difficult to interpret It could merely indicate that mesothelioma patients come from cancer families Experimental studies suggest that the histological response to asbestos varies with different animal species and in man genetie factors might alter suscepubility to mesothelioma This 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. J. V. REFERENCES 1. Schkeit 1 Churg J Hammarad 1. ve Hadagical Filaan of Arestim LA KC Nekuntiin Publication ma 3 edited b 1" Hoguski L. tulum and Timbecik C. Wagter op 209 Lisen 1979 2. famer 1973 LIES G~ 3. Wagner J. C. Shen G~ Marchand 1" Sr. J. ind Steal 1940. 17 2611 6. Ngu^-ana1. p H. j~ ra 1966 22. 284 ' Lallington Xi A. Jamp^nH. Dv^'fetshng New gf J.3kJ 1975 : 291.583 6. ChampiP.oAnm Rev mp Ou 1971 103 32t 7 McDonald A Q. Harper A. El Attar Q. A. McLumald J. C. Canert 26,914 1930 26,914 Roca 1. Heller A. Mh Janower L , Weber A. Ann J. Roca 1970 108 53 * An^chunil din Baum M F3 F3 | Slikod l^n NY Akad Ser 1978 271 311 30. Hanulum A Flandr JL L. Inglustrial Turnovlogy p 421. Actum Stannar . chuwits 1974 11. Barrios 1" Goden Goden occup Ave. 1972 11 135 12. Mc5E7w1an J. Finkayson Finkayson A. Air A Gibson A. M. Er med J. 1970 iv 13. Edge J. J. omvir Res 1976 19 244 14 Mellonaik J. ~ iibolagical of bifects Asberes LA.R C. Scientific Publica- tun mas radiced 1" Mogorski C. Gulum & umbrell and J. apher . 149 f.sam 1973 15 New Hope Lashid p cot M. 1977 321 In th well Sevit 1 Kinana Phuman 17. Jones J. 5. P. Poniry D. Smeth P. G. FAR 337 C. Inimm 1974 52 117 18. Nichelsen W. J. Ave.Y. Arad Sen 1976 231 112 19. Meltonaki 106 Heckkake M Uebb G. \ _ McDonald McDonald A. ] Konseri ^ ^ nbe seen Hick 1971 61 20. Tingevil Van Van Hubertal kafects ul Asbrum LARG Senate l'abbazarum ne for vet^rtid Poraneku C. KishanV. Tumbreanld lJ. G. MONT ? 244 him Iw / TA Kombat & GPS GPS Ticino 1971,5,279 1971,5,279 F turborne Infection 92. New U2 7. 7. O'Graz ^fin p York 1961 cd Gan 9. os TLT TLT TLT P Tother E. B. Kuchuk M. Babya M. A. Arens Hish 1967 15 343 24. Lynch ML Melver A. Cain J. R. Archs md S^>lik 1997 19 207 15. Reeves A. L. Puma H. E. Smith G. VorwalAd. } Enow Rev. 1971 4.196 CLOSTRIDIUM DIFFICILE AND THE ^ TIOLOGYOF PSEUDOMEMBRANOUS COLITIS H. E. LARSON P. HONOUR B. PRICE Clinical Research Centre and Northwick Park Hospital Watford Road Harrow Middleses HAI JUJ S. P. BORRIELLO Bacterial Metabolism Research Laboratories Public Health Laboratory S 'remeColindale London NWP SHT Summary Bacterial isolates from $ patients with pseudomembranous colitis P.M.C. were screened for toxin production Strains of Clostridium from 4 patients produced in vitro a town similar to that found in F.m.c. fr^calsuspension These were identified as C. difficile Use of the strains from 2 patients induced a fatal enterocolitis when inoculated orally into hams-