Document xjyRBepGLOmvQLnQJYq3wEqwQ

.^C*T,J aswarv 31, 1976 'i-oolchiJdrcn wr<r1 -ludc,, ,, , ' ,` ' grandio^^jlfi ,^"n5UJ^ ' trs endiojJSW Piho/ojy^J t en',,PorJ^' e reported, --niy mj[!cri w"*\ ^'"aoofflprewg :r ke King C * ,c-v niihediTIl* '0UI gain. sctJ of reference values, utilising fractilcs or s.D. units, has the great advantages that most measurements ,S,enis can b expressed in the same way and that the 1 of !r?rent examinations can be combined into a 3nce.' nor- .aution: "cut-off limits*' or "discrimination jh - 2 s.D. are arbitrary. In some cases it may ^ good for the patient to have a value falling outside ^ limits (e.g., below --2 s.D. for blood-lipids). complex problems of reference values are being dis- ` jt,' the Expert Panel on the Theory of Reference Values ^ International Federation of Clinical Chemistry. The , eicomcs suggestions on the use of reference values and **jj be glad for the discussion to spread to hsematologms finical physiologists. The panel hopes to publish a rccom- **Jinon shortly and can already distribute some unofficial cr.al A-? -Jiiorial* in Clinical Chemistry provides useful , l v -- .utuie io u Kf', Jf--- *Kt*iju*. Helsinki 10, Ralph Grasbeck t^r-an. Expert Panel on (he Theory of Reference Values, I.F.C.C. v*Utjfc ;-vAtCES^|' 'tan of rtp^L /S-P0 or joH^ esi.or i-enaoi'jU^ : S ouidtind. ' -`Uni, Boa-pc^iir. /** hctn coOeej a' : echnieW/SS-:' ". ition, usd -anly javtlidtuSt^-' " Proem in >" mu to} (_ witb "rrfenaB.- H --u*er ivimnnienul csAt^ 1 ioai mctiod i laicuiitiost 'j3?t " "aonsi] rihjS^ -Pulaiiom crfriBj i when it a ( d in many j : it in sa a a inilcad oft nuteiy 0025 I he use of ia iuues for r2 j.. fori rJ we aoiy i i Of ` i niic healthy i . reined to I own N : .o ibofcdTi the other 1 :"vo with t 4 ** '1.^ bright (Dec. 20, p. 1261), Professor Lennox Vv. 29, p. 1085), and others have written on the subject of ta^uhsaiion and units in laboratory medicine. Apart from ar Jiihcuir.s' :rv.?.ilcd in educating clinical and research phys- r,< jo : `bot for the wheel in matters methodologi- rorm-. ffers from a serious built-in disadvantage: t depends upon tr.c availability of a normal mean value which siiversally accepted. Tc must accept the fact that normal mean values are liable change with lime. Further, it is not unusual to find normal ecaa values differing from country to country and from region rtpon within a country--even from hospital to hospital mhin a given city. As a technique for evaluating, interpreting, and extracting fail information from clinical data, normalisation is useful and catruaive enough to be made mandatory. As a standard aribod for rererting (and thereby storing) data in the litera- tet it is r... :.p:able because the data become derived, rnber than . measured, quantities that arc dependent a consensus definition of normal mean values which can with time. T%o useful functions are at stake here--and what serves oc auy very- well not serve the other. ^r-.-aret ol Medicine ard Ijtontoryefihe *** *-'J School. Beth. Israel Hospital. 0;:i5. U.S.A. Bernard J. Kassil NORMAL a 10 r 2 -i -- vine to have such a rigidly defined concept aofTna!uy *> luridly expressed fey Professor Lennox* and by Dr Wright.5 To take the normal of hemoglobin r.rh _ Cause " '*'** historical precedent does not make ik !1 row* fl ** a pardcularly imeresung unit of normality, ^^*as originated by Haldane h a miser small series ("My *?ucr\-rl" r^X'--^*oush this oxoaian quotation may be <ai*ap 3 '* *uCT**ts iba; if certain biographical ** anj *?rcscme^ 10 l^e laboratozy, then normal ranges for **hcn 3^?C <m8' ^s0 ^ computed. This is, in fact, how ruen'i^., arc rc?ned ifl this institution, and the 1 jrC.Vrs.Oum. 19?;. 21. 1S?3. H 19-;.u.,0,. Much of clinical medicine is now committed to using labora tories for monitoring a patient's condition rather than for diagnostic purposes. Is there a normal haemoglobin for a neph rotic patient or one with chronic lung disease? Changes in absolute values or trends are far more cause for concern or rejoicing than their relationships to statistical or mythical nor mality. The need for an absolute value may be founded on groundless fears, but this proviso was placed in Dr VTright's opinion poll. Medical literature is likely to become chaotic, while half the world will be using SI units with the rest hardly even knowing what they are! With deep respect to my colleagues, I should like to suggest that we do not need yet another frame of reference with which to assess our patients. Surgical Intensive Care Unix, Mount Sinai Hospital. Sew York, N*ew York 10029, C.S.A. Christopher VP. Bryan-Brown ANGIOSARCOMA OF THE UVER IN P.V.C. FABRICATORS Sir,--Since the beginning of 1974 a number of cases of the rare tumour angiosarcoma of the liver have been reported amongst workers exposed to high concentrations of vinyl chloride, a chemical used to manufacture the plastic polyvinyl chloride (p.v.c.). Exposure to much smaller amounts of vinyl chloride may also occur when the raw p.v.c. is used to fabri cate plastic articles, as residual amounts of untreated vinyl chloride may then be released. Epidemiological studies of p.v.c. manufacturers have been set up in several countries, and the risk of occupational exposure to different levels of vinyl chloride will eventually be evaluated, but it is not known whether there is any risk to P.v.q. fabricators. The Office of Population Censuses and Surveys (O.P.C.S.) categorises per sons employed in extruding, moulding, cutting, and turning or otherwise machining plastics,1 which includes p.v.c. fabri cators, under the title of "workers in plastics" (occupational unit code 90). An analysis of death certificates for workers in this category should be a guide to the mortality pattern of plas tics workers overall and, by inference, to the effects of vinyl chloride in p.v.c. fabricators. The last published rates for plastics workers showed no sig nificant excess of deaths in any of the given disease categories, the standardised mortality ratio being 78.; Because (he figures for 1971 are not yet available we decided to undertake a pro portional-mortality study using death certificates for 1970-72 to detect any recent change in the pattern of mortality which may have occurred and be ascribablc to vinyl-chloride expo sure. Death certificates for male plastics workers, 1970-72, were coded by the O.P.C.S. according to the International Classifi cation of Diseases, eighth revision. Age-standardised propor tional-mortality ratios were calculated for each cause of death in ten-year age-groups, expected rates being obtained from mortality data for England and U'ales for each year under study.5 Approximately 60 000 men were recorded as plastics workers at the last England and Wales population Census/ About 35 000 of these (60%) are thought to be partly or wholly engaged in working with p.v.c. (based on H.M. Factory In spectorate records for 1975). As show'n in the table the only statistically significant 1. Office of PopuUtioo OnfRic nd Surveys. Qassiftcaiion of Occupattc.-t. H.M. Stationery Office. 1970. 2. RefMWtrCcnerti. Decennial Suppksncst England and U'alcs 1961: occupa tional mortality tables. H-M. Stationery Office. 1971. Registrar General. Stamtieal R<ros f England and Uslcs for 1970, I?':, and 1972: pan I, tables, medical. H.M. Stationery Office. 4. Office of Population Censuses and Survey Census 1971, Great Bniatn: eco nomic activity tables pan m, KTr sample. H.M. Stationery Office, 1975. T00SSZZZ BFG19756 246 THE LANCET, JANUARY excesses for the causes of death were stomach cancer and dis eases of the urogenitary system. The number of deaths due to all cancers were slightly higher than expected but there was a deficit of lung cancer and oniy 1 death from liver cancer (certi fied as primary carcinoma). There were 3 deaths from liver dis ease, with 3-6 expected. The deaths from diseases of the urogenitary system were analysed further into those due to nephritis and nephrosis (l.C.D. 580-5S4); there were 10 deaths in this category with 5-6 expected, a difference which did not quite attain significance at the 5% level. Fewer deaths than expected were attributed to neoplasms of lymphatic and hemopoietic tissue. The excess deaths from cancer of the stomach and diseases of the urogenitary system were surprising because vinyl KALI PLASTICS WORKERS'. DEATHS FROM ALL CAUSES 1970-72 Cause of death {l.C.D. no.) All cancers (140-239} Stomach* {151) Lim (1553 Lung (162-1 Brain {191/ Lttnphaiic'harmcpotctie (200-207) Endoer/nutr.'metabolic (240-279) Circulators- (390-451) Itchznic ,410-4)4': Rcspiraiorv 1460-519' Bronchitis (490-491 / Digestive (520-571) Liver,570-573; L'njfcaiurv* (580-629) Acodcms {900-949) Suicides -;E950-959) All other causa AU V<0 05. Obs- (O) Esp. (E) 204 185*9 24 16-4 1 It 88 99 3 5 5-0 3 15-2 4 6-2 345 336-0 229 225 0 77 80*0 42 J4.4 14 17-1 3 36 15 81 24 36 8 5 11-8 19 25-1 707 707-0 O/E 1-1 1-5 0-9 0-9 1-0 02 06 1-0 10 1-0 08 0-8 08 1-9 06 0-* 0-8 1-0 angiosarcoma of the uver Ti Sir,--The reports of hsemangiosarcoma of the liver* pie exposed to vinyl chloride1-7 led us to investigate .a**?* ation in Holland. We asked ail pathology laboratories throughout the co!l to allow us to study their cases diagnosed as angiosarcom?^ allied conditions). This yielded information on and tuSfr 27 adults seen since 1950. There were only 8 definite(7^* * and 1 possible angiosarcomas of the liver. In addition 1 sarcoma was present in a woman on long-term arsenic taed? tion--a well-known association.1 f Angiosarcomas asscSti with Thoroirasi'* 11 were not considered. 2 other anS?? comas originated in the spleen. There were 14 noo-vajc!w tumours of miscellaneous origin, and in 1 case no tumour W seen. Histopalhological details will be given elsewhere. AgT death of the 8 angiosarcoma patients varied between 46 ^ 73. One man (aged 56), who had worked for 15 years zinc-chromate primers under primitive circumstances, % seminoma at the end of this period and a malignant ^ tumour of uncertain histogenesis more than 10 yean Luo. The incidence of liver angiosarcoma is difficult to esumau.* Rein and Huth1*2b3ad4 65 c6a7se*s9in10310101729 1n3ecropsies. Our 8 aaa occurred in a fluctuating population of 10-14 million, with least 40 000 necropsies. Remarkably, none of our 27 patiass bad any traceable contact with vinyl chloride. j We are grateful to all pathologists, surgeons, internists, and gtacri) practitioners who cooperated in compiling the dau on the 21 patients. Factory Inspectorate (DGA), Voorburg, P.8. 69. St. Lucas Hospital, Amsterdam. University of Utrecht. Municipal Hospital, Arnhem, HoUaod. L. M. Dalderut t- S. C. Fmsi G. Bras F. B. Brosckhorsi chloride has not jo far been linked with either of these condi tions. However, a wide range of other chemical substances is used in the plastics industry, some of which may eventually prove to be carcinogenic or nephrotoxic and giving rise to these excesses. When interpreting a study of this kind it must be remembered that a proportional excess in a disease category may not reflea a real increase in death-rates over a compara tive population, but may also arise if there is a deficiency of deaths in other categories in the study group. Vinyl chloride has been suggested as causing cancer of the lung and brain,-' as well as angiosarcoma of the liver and other liver diseases.* In this study the observed numbers of deaths from these causes were not in excess of those expected. Any excess mortality from these causes which may be present in r.v.c. fabricators is consequently not large enough to be detected amongst plastics workers as a group. This is not to say that there is no excess risk; this study was undertaken to assess the order of magnitude of any excess risk as quickly as pos sible. However, recent studies of r.v.c. manufacturers also show little indication of an excess risk of lung and brain cancer associated with exposure to vinyl chloride.'' Health and 5iftty Executive, Employment Medical Advuory Sc-vice, l Chepstow Place, Loodoa V2 4TF. Office of Population Ceiuusa *ad Surveys, Medical Statistics Dmstoe, St. Catherine House. 10 Kiafvway, London WC2B 6JP. P. J. Baxter A. J. Fox 5. Moosoa, R. R., Peters, J. Johnaoo, M. N. Lancet, 1974, u, 397 6. Tbotaas, L. 8., Pepper, H,, Bert, P. Dn Sdikoff, I., Falk, H. Engl, jf. Med. 1975,292, 17. 7. Duck, B. W,, Carter,). T,, Cooobes, E. J. Lancet, 1975, ii. 1197 I. Fox. A. {., Colbcr, P. F- Tbe Mortality Experience of Workers Exposed to Vmyi Qdonde Mooooer m tbe Manufacture of Polyvinyl Chionde ic Great Britain. .'Uopubi-irvcri . SELECTTVE IgA DEFICIENCY T Six,--You state-1' that there is no difference in the frequency of sinopulmonary infection in healthy semm-lgA-deficieni peo ple and healthy blood-donors. There are two different forms of IgA, one in the serum and the other in secretions such u saliva, gastric juice, tears, and colostrum. They differ in that the secretory form is produced locally by the plasma-cells is the submucosal tissues of exocrine glands, whereas serum IgA is produced by circulating plasma-cells. The local plasma-cdb continue to funaion independently of circulating plasma-cells. The IgA produced locally differs from scrum IgA in that it con tains an extra antigenic chain known as the secretory or trans port piece as well as the heavy and light chains normally pres ent in serum IgA. The transport piece is secreted by the columnar cells and joined to the IgA molecules as they pass between the cells. Because of these differences, 1 think it would be unwise to suggest that IgA deficiency is not associated with recurrent infection unices local secretory IgA activity in pa tients with low-serum-IgA has been assessed. Saint Laurence's Hospital, North Brunswick Street, Dublin 7, Ireland. MICHAEL FARRELL 1. Lee, F. I.. Harry, O. S. Lancet, 1974, j, 1316. 2. Bntish Medicaljournal, 1974, i, 390. 3. 8niuA MedicalJournal, 1974, tv, 486. 4. Falk, Creech, J. L- Heath, C. W., Johnson, M. N,, Kcv, M. N. / Am. mcd.Au. 1974,230, 39. 5. Creech, J. C, Johnson, M. S. J. ecaup.Mtd. 1974,16. 150. 6. Unfe. C. ., JQhe, $,, Veltman, G. Dt. mad. Wtchr. 1974, 99. 1591. 7. Ravter, E., Dim, J, M., Pialat. J. Archt. Mel. pro/. Med. tree. 2975, 36, 171. I. Roth, F. Zentbl. Path. path. Anal. 1953,93,424. 9. Rcfeisoo. Kim, U., Aspina, Holland, J. F. Cancer, 1968,21, 5 M. 10. MaeMahon, H. G.. Mutphv, A. S, Bates, B. I Am J. Path. 1947, 23. 585. 11. Taluk, H.. Hardin, V. A. Ardu Path. 1955,60. 493. 12. Rein, F. R., Huth, F. fnt. Arch. Arbtitrmed. 1975,14, 237. 13. Lancet, 1975, ii, 1291. BFG19757 \ it