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LANCET 'y LANCET t LANCET if LANCET if LANCET F. No. 8026 BOSTON MASS AND LONDON SATURDAY 25 JUNE 1977 VOL I FOR 1977 : 1g ORIGINAL ARTICLES in - Maternal fetoproteinMeasurement Antenatal Screening for Anencephaly and Spina Bifidain Early Pregnancy U.K. Collaborative Study False Economy in the Laboratory 1363 Prof. Wright Infantile Gastroenteritis 1323 Detection RRootatvirausvirus Dr D. J. Ellens Dr W. de Lecuw 1363 a Rehydr Evaluation of electrolyte Solution for Oral Rehydr . Infantile Diarrh a Asok Mahalanabis Chat erje S. Dilip Chatterjee K. M.B. M.R.C.P.E. T. Maitra M.B. Agarwal F.r.c.s. D. K. Bagani S. Indra M.R.C.P.E. Determination Determination by Specific Antibodies 1333 Dr S. Delia and others Chronic Familial Vascular and Encephalopathy Dr D. L. Stevens others Merozoite Vaccination of Douroucouli Monkeys Against Falciparum Malaria /A. G. H. Mitchell PH.D. W. G. Richards PH.D. G. Cohen Prof. S. M.D. 335 Cromolyn Theophylline and in in Asthma CromoglyCromogclycate ate Dr Miles Weinberger ; Immunoreactive in Somatostatin Pancreatic Islet Carcinoma . Immunisation with a Polyvalent Pneumococcal vaccine D. Riley M.R.C.P.E. P. I. Tarr A.B. M. Andrews B.SC. Douglas M. Pfeiffer B.SC. R. Howard M.B. P. Challands G. Jennison M.B. R. M. f.r.a.c.p. D Comparison of Oral hydroxycholecalciferol Vitamin hydroxyvitamin and Ultraviolet Light as Determinants of Circulating 25 : D= T. B. Stamp M.R.C.P. J. G. Haddad M.D. C. A. Twigg 11338 1341 . Accompanied by Ectopic A.C.T.H. Syndrome Dr K. Kovacs and others Overdia ofgEnn doo crisneiGs ut Tumours Modlin f.r.c.s. Dr S. R. Bloom with Cimetidine Long Long DuodenalTreatment with Cimetidine Prof. Porro Dr M. Petrillo 1364 1364 1365 1365 1366 1366 REVIEWS Notices of Books QUESTIONABLE ROUTINES Prophylactic Antimicrobial Therapy Hospitals at Drug Five Teachingthe London Teaching Group on Hospitals Use of StudyAntimicrobial DrugDrusgs ; . OCCASIONAL SURVEY Relation Between Smoking and Age of Natural Menopause Hershel Jick M.D. Jane Porter M.S. A. S. Morrison M.D. POINTS POINTS OF VIEW The Law and the Juvenile Donor C. M. Clothier Q.C. COMMENTARY FROM WESTMINSTER Secure Units for the Mentally III Violence to Children . OBITUARY DesmDonedsmond Desmond FrFarnacnicsis O'NeiO'Nelill l NOTES AND NEWS for Family Planning Priorities Planning the PlansPlansforfor theMenMteantlallyly Handicapped BackBBack ack Pain Cigaret e Advertising Curbs on Cigarette Advertising University of Newcastle upon Tyne University of Birmingham Lady Tata Memorial Trust Association of Community Health Councils for England and Wales 1343 1350 1353 1355 1373 1374 1374 1374 1375 1375 1376 1376 1376 1376 - 137 Endoscopy versus Radiology in Acute : . Screening for Neural Defects Valid Parental Consent Atherogenic Hormones Cosmetic Talc Powder H^mophilus Endocarditis H^mophilus H^mophilusEndocarditis Medicine Journal of Medicine 1345 1346 1347 1348 1349 1350 gastrointestinal Bleeding Dr Urography Intravenous Intravenous UrographyUri ogn raphy the Management of Acute Retention Dr Bryan Donnelly and others Schizophrenia and Rheumatoid Dr and others Tryptophan ^ sterberg TryptophanTryptophan anidn Monoamine Cerebrospinal Ventricular CerebrospinalCerebrospinal Fluid after Severe 1367 1367 1367 1367 1367 CeDrrebral Trauma Hyypp^/and otohthersers 1367 LETTERS TO THE EDITOR Definition of Perinatal Mortality Dr M. Dunn Mr Wilfred Mills F.R.C.O.G. Endometrial Mack Replacemnt Hormone Replacement TherapyTherapy and Carcinoma , Dr M. Pike . ; , 1357 . 1358 Treatment of Cushing's Cyproheptadine Disease and and otheothersrs with induce inducd ed CCuusshhiin ng g' 'ss Cushing's Syndrome Dr Anthony Smals PrProoff. . PePetetr er KlopKlpoeppnebnoborrgg : Rebound Thrombocytosis after - Alcohol Currie , 1368 1369 1369 and Postmenopausal Oestrogen Replacement Li ids Dr Ulf Larsson Duchenne's Dystrophy Prenatal Dr L. Rutkowski and others phosphatase Activity in Human Placenta Possible Detection of Heterozygote for Glycogen Disease Type I Dr Reuben Matalon and others Aplasia Selection of marrow Patients for Allogeneic marrow Transplantation , Prof. G. Math~ Dr .. Schwarzenberg Combined HLA Antigens and Severe Combined IDmrmAu.nA od.efRiicmimency Disease Dr M. M. Hortin and Dia cholesterol annel and others os . ent Immobility F.K.C.S * . , F.R.C.S. Dr A. Kaegi . 1358 and Alcohol Head Injury Dr R. Patel and others Is Bone Loss in Chronic Renal 1359 ~ 7 1360 1361 Failure dependent Dr Claus Christiansen and others Eskimos and Multiple Sclerosis Simultaneous Bacterial Viral Simultaneous Bacterial and Viral Meningitis Squadrini Prof. F. Squadrini and others Bacteroides fragilis Meningitis Klebsiela Dr Chattopadhyay = Klebsiella meningitis Treated with Intrathecal Amikacin 1361 Dr C. S. Block and others Phenytoin LympLhadyenmopapthihesaDd.enLymophapdenaopatthihes iaensd and Phenytoin others 1362 Spontaneous Fracture T Spontaneous Fracture of Mr W. Gillison F.R.C.S. PoPloylvyivniynlyl 1363 Effect of Distress on Factor Activity Dr G. Nenci Dr G. Agnelli 1369 1370 1370 1371 1371 1371 1372 13731373 1373 . She aree s: e! Editorial Office 7 Adam Street London WC2N 6 Brov '. te American Edition published weekly by Little Brov 34 Beacon St. Boston Mass 02106. In U.S. and CambanCamban subscription 30.00 resident and intern rate 21.50 single c 4.00 Second class postage paid at Boston Mass and at additic mailing offices 'The Lancet 1.td. 25 June 1977. Notifica on Form 3579 is to be mailed to The Lancet 34 Beacon Street } ton Mass 02106 THE WHOLE OF THE LITERARY MATTER IN THE lancet is COPYRIGHT 20 U1111 seste LI LI ORTHO ORTHO DIAGNOSTICS DIAGNOSTICS DIAGNOSTICS DIAGNOSTICS ATTN ATTNATTN LIBRARY LIBRARY LIBRARY LIBRARY LIBRARY LIBRARY PO BOX 23097 K RARITAN RARITAN RARITAN RARITAN : 4072008407208 INC ey ? L NJ NJ 08869 08869 08869 08869 717 717 Lasse 2764 147 147 stam geet ee eee see TR cere te orem et ee PIE TN SR at Ge ene mene wane ' 18. iz 4 3 i u r } i f 3 . : . 3 i t : . : d j , a ' 1 2 i ae 5, & : 4 & z a = fe u B ty x NEWSPAPER E NEWSPAPER B is NEWSPAPER ies . 1 NEWSPAPERNEWSPAPER i NEWSPAPER if NEWSPAPER o NEWSPAPER if NEWSPAPER . NEWSPAPER a ee iP ie Ee ie |ig * z i* le IE 2 nee, JJNJNJ Q0030592 Q00030592 1348 THE LANCET JUNE 25 1977 subjects whether manifest in the fasting or in the stimu- Although talc can cause granulomas when introduced lated state is independent of coexisting obesity and glu- into the tissues or body cavities cose intolerance although both are often contributory factors Which is chicken and which is egg is unresolved exposure to cosmetic tale has been widely assumed not to predispose to pul- fibrosis but experimental evidence favours a causal role for monary However the fact that no association has been seen between the use of talc and loss of lung of shuylpienritonsaunliimnaelmsiain continued administration in- function might simply reflect the lack of methods sensi- Ty 25:3: optimal doses can give rise to tive enough to detect losses of function that small histological and biochemical lesions resembling those of compared with those due for example to are tno, human atheroma and insulin encourages the synthesis smoking and to heterogeneity in antritypsin status For similar of cholesterol and other lipids by arterial tissue sons any effect of talc rea- both in vivo and in vitro Of the many factors known to would exposure on cancer incidence areas cause exaggerated insulin secretion such probably escape notice unless deliberately sought some and high sucrose consumption have been as obesity Until lately facilities for studying the term effects of ied implicated inhalation of dusts in laboratory animals have been on epidemiological grounds in the pathogenesis of ath- scarce and even now the erosclerosis whilst others such as increased consumption models is questionable predictive value of animal of sugary alcoholic drinks have so far not been Con- Thus even in the case of tobacco . niEerh versely certain types of vegetable fibre the exclusion smoke where the cancer hazard to man is indisputable from the diet of which have been claimed to increase the duplication of the effect by the inhalation route in impossible risk of atheroma reduce the immediate and laboratory animals has proved difficult or a overall in- although inhaled asbestos dust has given positive results sulin secretory response to ingested carbohydrate with- in animals nh out adversely affecting glucose tolerance The role of the The possibility that talc causes cancer insulinotropic gastrointestinal hormones in providing dramatically hit the headlines of the daily Press when workers in WEN the link between composition of the diet and the hyper- diff reported finding talc particles in Car- of the insulin^mia of atherosclerosis is undetermined and and uterine cancers ae awaits investigation by the newer methods of ovary cervix The report was greeted with them in blood measuring scepticism because the particles were not positively iden- tified as talc because their presence did not prove causa- tion and because they might have found their way onto the sections as a result of contamination of tissues after removal from the body Subsequent mineral analysis failed to confirm that the particles were tale and the eas passage of six years without publication of ey, confirmatory evidence suggests that the early scepticism was well- Sane,orbs COSMETIC TALC POWDER founded A meeting of powder manufacturers and nwerte20S From time immemorial man like his evolutionary independent scientists took place at Cardiff during May 1976 under the chairmanship of Dr J. C. Gilson direc- Esc predecessors has been exposed to airborne dusts Such tor of the Medical Research Council #: exposure is a corollary of living and survival Not unex- Unit At that Pneumoconiosis ca eryere pectedly therefore the lungs have efficient means of meeting the toxicology of talc was ey reviewed and the need for further information discussed clearing themselves of inhaled particles and a functional marty reserve such that the accumulation of uncleared dust Assessment of toxicity necessarily starts with a consideration of the physical and chemical may be considerable before there is any obvious loss of specifications of the test material and this unfortunately is also where capacity However it has long been recognised that heavy exposure to dusts such as quartz and much of the assessment ends in the case of cosmetic talc because most of the published epidemiological asbestos may lead to loss of function and in the case of clinical and experimental asbestos to cancer of the pleura and of the lung itself industrial tales that exposure either to The observation that even casual are variously contaminated with exposurteo asbestos may be associated with increased risk of minerals known to be hazardous or to talc of undefined mesothelioma physical and chemical characteristics now occurring at the rate of nearly 200 new cases a year in the United Kingdom has brought into question the The long thin fibrous shape enables them be carried more of asbestos into particles safety of other common dusts such as cosmetic talc than deeply the lungs There are two main concerns Firstly will inhalation of sphericalparticlessphericalparticles of similar mass The fact that the normally effective clearance mechanisms have a dust cause loss of function through fibrosis or emphy- sema difficulty in coping with large long thin particles de- And secondly will it predispose to cancer posited deeply in the lungs is an important determinant 10. Sloane M. Mackay S. Sheridan B. ibid 1970 ii 586 11. Kashyap M. Magill P. Rojas .. Hoffman M. Can med Ass 1970 1970 102 116S J. : iii 12. Stout R. W. Bierman E. .. Brunzell J. D. in Diabetes its Physiological and Biochemical Basis edited by J. Vallance Lancaster 1977 13. Stout W. med 1970 685 14. Stout R. Fencer 1969 it 467 of the hazards from asbestos dust Geologically talc which is nominally a hydrated magnesium silicate and certain amphiboles actinolite and anthophyllite occur in juxtaposition and consequently talc may be contaminated with these minerals Apart 15. Sto1u5t3 W. Buchanan K D. Vallance J. Atherosclerosis 1973 18 J. 16. Szanto Yudkin Postgrad Postgrad med 1969 45 602 O'Keefe D. Marks V. Lancet June 18 1977 1286 18. Gleave 1.f. p The Saccharine Disease Bristol 1974 19. Jenkins D. A. Golf D. V. Leeds R. Alberti G. M. M. Wofever . M. 1. M. Gassuli A. Hockaday D. R. Lancet 1976 ii 172 1. Greenberg M. Floyd Davies F. Br J. ind Med 1974. 91 J. 2. Bluemel G. Piza F. Konorsa W. Wien klin W'schr 1962 74 12 3. Davis R. Whitehead J. K. Gill M. E. Lee N. Butterworth A. D. Roc C. Br Cancer 1975 31 469 4. Wagner C. Berry G. Skidmore W. Timbrell V. ibid 1974 29 252 Henderson W. J. Joslin C. F. Turnbull A. C. Griffiths K. J. Obstet Obstet Gynec Br Comonte Commonte 1971 , 78 266 6. Hildick Smuth Y. BrJ. ind Med 1976 217 ve SUNJ SUNJ 000030593 THE LANCET JUNE 25 1977 . . from this tale may contain chlorite quartz carbonates such as calcite dolomite and magnesite and occasionally other minerals in lesser amounts During the past few years major cosmetic manufacturers in the United Kingdom and the United States of America as represented by the Toilet Preparations Federation and the Cosmetic Toiletry and Fragrance Association have drawn up specifications for cosmetic tale which ensure the virtual absence of fibrous amphiboles At present there is no direct statutory control of the quality of cosmetic tale in any country and it is questionable whether such control is necessary to bring minor manufacturers into line with the standards now adopted by the major firms The presence of fibrous particles in talc reduces its free flow and lubricity thereby rendering it less cosmetically desirable Such contamination is thus limited More important however is the fact that the fibrous materials most likely to contaminate talcs which do not comply with the specifications tremolite anthophyllite and actinolite not those most clearly associated with carcinogenic hazard crocidolite amosite and chrysotile Furthermore it would be sen- sible to consider what controls if any are necessary for talc as used in medicines before introducing legislation specifically in relation to cosmetic talc If the inhalation of particles of amphibole and silica contaminated talc dust were found to be harmless one might reasonably assume that talc free from these materials is safe Kleinfeld and his colleagues have studied the incidence of cancer and respiratory diseases in tale miners and millers in New York State The talc con- cerned which is heavily contaminated with both amphiboles and free silica was initially reported to be associ ated with an increased mortality from mesothelioma and vor pulmonale Later the same workers reported that men employed in the mine after dust levels had been reduced had death from malignant discases that were similar to those for White males in the U.S.A. generally Also in the U.S.A. Fine and his colleagues,, have reported a higher prevalence of productive cough and chronic obstructive lung disease among rubber workers exposed to a fibrous industrial talc than among control workers From their data they calculated that a safe exposure level would be provided by a threshold limit value of 0.25 mg respirable particulate talc In Italy Rubino and his colleagues14 compared the spectra of causes of death among talc miners tale millers and agricultural workers The talc miners were exposed to dusts containing % silica at levels far in excess of threshold limit value Significantly more of them than ofthe controls died from respiratory disease but death from all forms of cancer includ- ing lung cancer were significantly lower among the 7. Toilet Preparations Federation Ltd. specification no 12 Cosmetic Talc 1977 8. C.T.F.A. Specification Tale Cosmetic Cosmetic Toiletry and Fragrance Association Inc. issue 10-7 1976 9. Toilet Preparations Federation Lad analytical method 77 Cosmetic Tale 1977 10. Hamer HE Rolle R. Scholz P. Am ind Hyg Ass J. 1976 37 246 11. Kleinfeld M. Messite J. Kooyman O. Zaki M. H. Archs envir Hich 1967,14,653 1967,14,653 14. Kicinfeld M. Messite J. Zaki11.7 11.7 occup Med 1974 16 345 13. Fine I. , Peters M. Burgess W. Di Beradinis 1. J. Archs envir Hich 1976 31 195 . 14. Rubino G. , Scansetti G. Piolatto G. Romano C. J. occup Med 1976 18 146 1349 miners than among the controls By contrast among the talc millers exposed to dusts containing 0.05 silica but no detectable asbestos at concentrations of 20 mil- lion particles per cubic foot 27 litres there was no excess of deaths from pulmonary disease or cancer of any site compared with the control group The deficit of lung cancer among the talc miners is plausible in so far as a similar deficit of lung cancer among coal miners seeins to be real A continuing study of over 3200 persons mainly women at a factory in Britain where cosmetic tale has been made and packed for over fifty years has so far revealed no evidence of health hazard but follow would need to be extended for at least a further decade before one could be confident of a nega- tive result Other less informative epidemiological studies are reviewed by Hildick In most of the work in animals the quality of the talc has not been specified An exception is a report by Wehner and others who studied the effects in hamsters of repeated exposure to aerosols of cosmetic talc up to total doses of respirable particles equal to nearly 2000 times those received by humans using cosmetic talc during baby care Exposure had no adverse effect on bodyweight survival incidence of pathological changes in the respiratory tract or incidence of neoplasia at any site Another exception is the report by Wagner and his colleagues who saw no mesotheliomas in 48 rats after intrapleural administration of cosmetic talc whereas 18 out of 48 rats similarly exposed to chrysotile asbestos acquired such tumours The same workers exposed rats to cosmetic talc by the inhalation route on five days a week for up to a year At the highest level of exposure aboutthree times that studied by Wehner and his col- leagues was slightly more pulmonary fibrosis than in controls but no substantial excess of pulmonary neoplasms A number of less relevant animal studies all of which gave negative results for carcinogenicity are reviewed by Hildick In summary there is no reason to believe that normal consumer exposure to cos- metic talc has in the past led either to cancer at any site or to measurable loss of lung function It seems unlikely that future exposure to cosmetic talc of the specifications now agreed to by major manufacturers will present a health hazard H^ MOPHILUSENDOCARDITIS H^mophilusendocarditis is rare Until lately the published reports were small and conflicting now three substantial and independent investigations have been reported from the United States 15. Goldman K. Br 7. ind Med 1967 22 72 16. Newhouse M. .. Miller B. F. Moore W. S. Paper given at seminar on Biology of Tale Used in Health Products Cardiff May 1976 17. Wehner P. Zwickei G. M. Cannon W. C. Watson C. R. Carlton W. Fd Cosmet Tox 1977 15 121 18 Wagner C. Berry G. Cooke T. J. Hill R. J. Skidmore J. W. in Proceedings of Fourth International Symposium on Inhaled Particles and Vapour Oxford 1977 1. Geraci J. E. Wilkowske C. J. Wilson W. Washington J. A. Mayo Clin Proc 1977 52 209 2. Chunn C. J. Jones S. R. McCutchan J. A. Young E. J. Gilbert N. Medicine Baltimore 1977 56 99 3. Lvni J. Kane J. G. Parker H. ibid 1977 56 115 a argrar . - OAHED PH VE SAE 000030594 And