Document KpY2ZpaE3xJxgk7mwD6RGVe0

- /"<l lAK'tlT.jANTAKt 31, 13176 20 or more >rHr>f rcfcrrnu- V jlno, milivini; fisct'lr* or unit*, 'litis *y*lcm Ion (he great mtinniapn that ntn'l measurement* on ]>tticnii can he ca|re%*ctl in the a**nr *nd im* 'he tesult* of different cuaminminn* can be rombmed into.* common tignificancc.1 A word of caution: "cut-olf timin'* or "discnromnon point*" mch a* 2 i.n. are arbitrary. In *ome esse* tt may even be good for the patient to have a value falling outiide three limit* (c.g., below --7 *.t. for blood-lipid*). The compte* problem* of reference value* are being dt*- cussed by the Expert Panel on the Theory of Reference ' *hte* of the International Federation of Oinical Chemistry. Tne panel welcome* suggestions on the u*e of reference value* and would be glad for the disunion to spread to hsemstologist* and clinical physiologist*. The panel hope* to publish a recom mendation thonly and can already distribute some unofficial material. An editorial* in Clinical Chemittry provide* useful information. Minerva Foundation InmtUic for SUdk*) Rewirth, l'.O.R, 819.00)01 Hrkmfci 10, Finland. Ralfm Grasbeck Chaimnn, Eipcn Panel on the Theory of Reference Values, l.F.C.C. Sta,--Dr Wright (Dec. 20, p. 1261), Profe**or Lennox (Nov. 29, p. 1083), and others have written on the subject of normalisation and units in laboratory medicine. Apart from the difficulties entailed in educating clinical and research phys icians to forego the foot for the wheel in matter* methodologi cal, normalisation suffers from a serious built-in disadvantage: it depends upon the availability of a normal mean value which is universally accepted. We must accept the fact that normal mean value* are liable to change with time. Further, it i* not unusual to find normal mean values differing from country to country and from region to region within a country--even from hospital to hospital within a given city. As a technique for evaluating, interpreting, and extracting full information from clinical data, normalisation is useful and instructive enough to be made mandatory. As a standard method for reporting (and thereby storing) data in the litera ture it is not acceptable because the data become derived, rather than directly measured, quantities that are dependent upon a consensus definition of normal mean values which can change with time. Two useful functions are at stake here--and what serves one may very well not serve the Other. Dcpuuncst of Mcdione nl Thorndike Laboratory ofthe Harvard Medical School, Both Itract Koapitai, Boaton. Matuchuactu 0211}, USA. BERNARD J. RaKSIL NORMAL -102 Sir,--It is disturbing to have such a rigidly defined concept of normality as so lucidly expressed by Professor Lennox4 and supported by Dr Wright.* To take the normal of hemoglobin as 100 because h was good historical precedent does not make it right now. It is a particularly interesting unit of normality, as it was originated by Haldane in a rather small series ("My fittest lab boy"--though this oxonian quotation may be apocryphal). Dr Wright suggests that if certain biographical data arc presented to the laboratory, then normal ranges for sex and age may also be computed. This is, in fact, how biochemical data are reported in this institution, and the system is trouble-free. i. SundcmuB, f. W,, Jr. Clin. Chtm. 197], 21,117}. t. Lrniw, B. 1975, ii, 10*5. 5. xrrigbi, B. M. iW p. 1261. Much of clinical medicine is now committed tn using UKiratones fnr monitoring a patient's condition rather than for diagnostic purposes. Is there a normal hrnioglohm for a neph rotic patient or one with chronic lung ducater 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 oo groundless fears, but this proviso was placed in Dr Wright'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 tike to suggest (hat we do not need yet another frame of reference with which to assess our patients. Surgical lmrmivc Care Uoii, Mount Sinai Hotpitil* New York, New York 10029, U.S.A. CHRISTOPHER W. Bn YAK-BROWN ANGIOSARCOMA OF THE LIVER 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 (r.v.c.). Exposure to much smaller amounts of viayl chloride may also occur when the raw r.v.c. is used to fabri cate plastic articles, a* residual amounts of untreated vinyl chloride may then be released. Epidemiological studies of r.vx. 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 r.vjQ. 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 plasties,1 which indudes 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 ofplas tics workers overall and, by inference, to the effects of vinyl chloride in r.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 78.1 3Because the figures for 1971 are not yet available we decided to undertake a pro portional-mortality study using death certificates for 1970-72 to delect any recent change in the pattern of rnoniiity which may have occurred and be asatibable to vinyl-chloride expo sure. Death certificates for male plastic* workers, 1970-72, woe 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 Wales for each year under study.* Approximately 60 000 men were recorded as plastics workers at the last England and Wales population Census.4 About 33 000 ofthese (60%) are thought to be partly or wholly engaged in working with r.v.c. (based on H.M. Factory In spectorate records for 1975). As shown in the table the only statistically significant 1. Office of Population Ccmutcs and Surveys. Clauificiuon of (XzupiViO&L H-M. Siisimo) Office, )9?0. 2. Registrar Gtncnl. Decennial Supplement England and Vila 1961: occupa tional monaliiy tablet. H.M. Stationery Office, 1971. 3. Rcgitirar General. Siaiitttcal Reviews of England and Vila for 19~Q, 1971, and )977. pan i, tables, medical. H.M. Stationery Office. 4. Office of Population Ccntutcs and Surveys Census 1971, Great Britain' eco nomic activity tables part tn, 10*< temple. H.M. Stationery Office, 197*. UCC 088301 -/ c 246 THE LASCLT, JANUARY 31, 1976 cictMO for (lie causes of death were stomach eam.cr and dis eases of the urugcniiary system. The number of deaths dvc 19 all cancer* were slightly higher than expected but there wit a deficit of lung cancer and only 1 death from liver cancer (certi fied at primary carcinoma). There were 3 deaths from liver dis ease, with 3-6 expected. The death* from dictates of the urngenitary system were analyied further into those due to nephritis and nephrosis (I.C.D. 580-58-4); there were 10 deaths in this category with 5-6 expected, a difference which did not quite attain significance at the 5% level. Fewer death* than expected were attributed to neoplasms of lymphatic and hxmopoietic tissue. The excess deaths from cancer of the stomach and diseases of the urogenitary system were surprising because vinyl MALE ELASTICS WOSXEXS: DEATHS FXOM ALL CAUSES 1970-72 Cfluui of death (LCD, no.) Obc. (O) *,.(E) Q/E AW ciKcn 040-2)9) Stomach* (151) Liver (155) Lun, (162-1 Brain (191) Lympbaiic/homopoicUc (200-207) EDdocr/nuirymeubolic (240-279) Circulatory (39IM5S) Ischemic (410-414) Respiratory (460-519) Bronchitis (490-491) Dijniive (520-571) Liver (570-571) Urogcniiary" (590-629) Acbdcnu (EIOO-949) Suicides (E950-959) AD other causa AS 204 JI5-9 1-t 34 16 4 1-5 I M 0-9 U 99-3 0-9 s 5-0 1-0 15 3 0-2 4 6-2 0-6 345 336-0 10 229 223-0 1*0 77 90*0 1-0 42 34-4 01 14 17-1 0-t 3 3-6 0* 15 *1 1-9 34 36* 0-6 I U-l 04 19 35 1 0-f 707 707-0 to -ECO-OJ. ANGIOSARCOMA OF THE LIVER - Sir,--The report* of hwmangiosarcoms of the liver in peo ple exposed to vinyl chloride1'2' *le*d us to investigate the situ, ation in Holland. We asked all pathology laboratories throughout the country to allow us to study their case* diagnosed as angiosarcoma (or allied conditions). This yielded information on and tissue* of 27 adults seen since 1930. There were only 8 definite (7 men) and 1 possible angiosarcomas of the liver. In addition ) angio sarcoma was present in a woman on long-term arsenic medica tion--a well-known association.* * Angiosarcomas associated with 'Thorotrast''* " were not considered. 2 other angiosar comas originated in the spleen. There were 14 non-vascular tumours of miscellaneous origin, and in 1 case no tumour was seen. Histopathological delail* will be given elsewhere. Age at death of the 8 angiosarcoma patiems varied between 46 and 73. One man (aged 36), who bad worked for 13 years with zino-chromctc primer* under primitive circumstances, bed seminoma at the end of this period and a malignant liver tumour of uncertain histogenesis more than 10 years later. The incidence of liver angiosarcoma is difficult to estimate. Rein and Huth" had 6 cases in 30 079 necropsies. Our 8 casts occurred in a fluctuating population of 10-14 million, with at least 40 000 necropsies. Remarkably, none of our 27 patients had any traceable contact with vinyl chloride. We arc graicful to all pathologists, surgeons, internists, and general practitioner* who cooperated in compiling the data on the 27 patients. Factory Inpwomt (DGAX Voo,burg, hB, *9. Si. Utn Hmpital, Amutirin University of Utrecht. Municipal Hoepital, Ambon, Holland. L.M. Daldercf S. C. Freni G. Bras F. B. Bronckhorst chloride has not so far been linked with either of these condi tions. However, a wide range of other chemical substance* i* used in the plastics industry, tome 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 reflect 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,5 *as well a* angiosarcoma of the liver and other liver diseases.* In this study the observed number* of deaths from these causes were not in excess of those expected. Any excess mortality from these causes which may be present in e.vx. fabricator* is consequently not Urge 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 E.vx. manufacturers also show little indication of an excess risk oflung and brain cancer associated with exposure to vinyl chloride.7 * 9 10 11 12 13 Health and Safely Ciccwm, Employment Medical Advitarj Soviet I Chcpeto* Ptaa, Undo* W2 4TF. Office of Population Cciuutcs and Survey*, Medical Smtinict Pivtoon, St. Catherine House, 10 Kioftway, London WC2B 6JF. P. J. Baxter A. J. Fox 5. Monsan, k. X., Peters, J. M, Jobneon, M. N. Lml 1974, ti, 397. 4. TTiomas. L. B, Popper, H, But, P. D., Sdikolt, |, Fell, H. AVt i Mti, 1975,292, 17. 7. Duck, B. W, Ctntr, J. T, Combes, E. J. Umctf, 1975, ii, 1197. *. F<w, A. J, Collier. P. F. The Atonaliiy Experience of Worlrr* Exposed Vinyl Oiloride Monomer in the Aianufanurr of Polyvinyl Chloride ia Creel Britain. (UnpuhtiilicS). SELECTIVE IgA DEFICIENCY Sir,--You stale'* that there is no difference in the frequency ofsinopulmonary infection in healthy scrum-IgA-defirient peo ple and healthy blood-donor*. There are two different forms of IgA, one is the scrum and the other in secretions such as saliva, gastric juice, tears, and colostrum. They differ in that the secretory form is produced locally by the plasma-cells in the submucosal tissues of exocrine glands, whereas serum IgA is produced by circulating plasma-cells. The local plasma-cells continue to function independently of circulating plasma-cdls. The IgA produced locally differ* from serum IgA in that it con tains an extra antigenic chain known as the secretory or trans port piece a* well as the heavy and light chain* normally pres ent in scrum IgA. The transpan piece is secreted by the columnar cells and joined to the IgA molecules as they pass between the cells. Because ofthese differences, I think it would be unwise to suggest that IgA deficiency is am associated with recurrent infection unless local secretory IgA activity in pa tients with low-scrum-IgA has been assessed. Slim Laurence1* Hospital, Karth Bnuiswidt Street, Dublin ?, Irdudf Michael Farrell t. Lee, F. I, Harry. D. S. Unto, 1974, i. 111*. 2. Briutk Mtiittljmntl, 1974.1,590. 9. British Medfc*!1974, W, 4$4. 4- Filt, H., Creech, J. t_ Heath, C W., John**, M- N-* Key, M. K.J- A*m*d.Au. 1974,2)0, 59a S. Creech* j. C, jobmoa, M. S.J. occup. M*d. 1974,1C, ISO. C. Lange, C. ., Juhc, S* Veluoao, G. Di. m*d. fTtckr. 1974,99,1591, 7. Revier, E., Dfter, J, M-, Piata, }. Artks. Mil. prof- Mid. fro*. 1975, 3L 171. 9. Roth, . ZtnibL Psth.pttk. A**s. 1955,93,424. 9- Rcgcitoa, tT.( Kim, U* Afpina, J., Holland, J. F. Cancer, 1961,21, 514. 10. MacMahon, H. G- Murphr, A S,, Bata, B. X.Am.J.Poth. 1947,2), 5S5. 11. Taluk, H-, Nocdia, W. A. Antu FciA. 1955,60,493. 12. Rein, F. JL, Huib, F, Ini, Arch. Arhritrmtd. 1975,34. 237. 13. Unctt, 1975, ii, 1291. t/Cc 088302 S