Document G6KaR9Mvw5dd9emZpY2rzq7YN

* T SASUARy^5' ctT, JANCARY 31, 1976 ctflokhiJdfll : *lader" a, ojs l5 of reference values, utilising fracules or s.D, units. **siein ^as l^e 8rcat advantages that most measurements ^'iicnis can be expressed in the same way and that the * '"* 0j- .afferent examinations can be combined into a ,Cate *h j* tlonal ^iSS* h;ai lcast uirifeS atioa ia^ W"Crc ' sJdiojjS?1 snee.' ^s:^or_ .aution: "cut-off limits'* or "discrimination - jU>:r, ji ~ 2 s.D. are arbitrary. In some cases it may 06 <X good for the patient to have a value falling outside g,5 below -2 s.D. for blood-lipids), complex problems of reference values arc being dis' j fev the Expert Panel on the Theory of Reference Values ** International Federation of Clinical Chemistry. The PathoJoj,^* * M lnpor*,|Sr: 'eriT*>nttL.22* _ fn/y matten Sjf- 1 welcomes suggestions on the use of reference values and be glad for the discussion to spread to hxmaiologists *^iinjcaj phvsiologists. The pane! hopes to publish a recom- shortly and can already distribute some unofficial ^er.sl An -Jiiorial5 in Clinical Chemistry provides useful gt.-CT.3V. I _ -tituie for . ke Kujg Ctj^Z . "? nishcdTT* ,oula&ain. teg*. .a .mu : Helsinki 10. Ralph Grasseck __iia. Expert Panel on the Theory of Reference Values, l.F.C.C. EVAL^ "VALUES Ft, , tem of ny^ /s-0.) or eqS3J JSSOr i-eoooz'g ^ '.^C' 5 ouidaiaLijng'-. - -<llal --j-ai'yf^v* ba oVU^-' ; echnioJ^-: < '---dtuajtirjS?.-:. -` Ition, ruf " warily invalid ' '' :* proect in > "isrs and c*kT wixb "rderctt^: :-- uscr bn A^ j :vL-Dnaienuli^2 '-! -caf method tad 'iJculauooi '/3& ~ '`normal n ipuianooj or, . when ii a d in many ^ t in sj. ics instead palely 0-025 be use of i .uues far z 2 s.d. for i "J we may' of i sale healthy txiited to ora '. .j tboli^'3 the other r'-ves with 5;x,__Dr Wright {Dec. 20, p. 3261', Professor Lennox v-v. 29. p- 1 OS5j, and others have written on the subject of arsjlisar.ur. 3nd units tn laboratory medicine. Apart from a* firScui:.' .-'..?.:!ed in educating clinical and research phys- f-,-, ,0 : -boi for the wheel in matters methodoiogi- , -ornu. ' ffers from a serious built-in disadvantage: t Jcpcr.J> upon tr.c availability of a normal mean value which aseimrsally accepted. Tt must accept the fact that normal mean values are liable i change with time. Funher, it is not unusual to find normal scan values differing from country to country and from region ,-rpon within a country--even from hospital to hospital vah;n a given city. Aj a technique for evaluating, interpreting, and extracting f*3 information from clinical data, normalisation is useful and structive enough to be made mandatory. As a standard rtboJ for rerorting (and thereby storing) data in the litera- wt it is r. t.ptable because the data become derived, ntier than .... .. v measured, quantities that are dependent *?* a consensus definition of normal mean values which can ctasgt wuh time. To useful functions are at stake here--and what serves ne =uy very well not serve the other. t***uo<w Ol Mediant and I^tvraiciy cf the School, Btih Is.-at. Hwpiul. k*^'''w^uino;:i;.c.s.A. Bernard J. R.ansil NORMAL = 10 z 2 s<*,--It cir.e to have such s rigidly defined concept , aCTTU-,:)' as so luridly expressed by Professor Lennox* and HxTkT To take lie normal of haemoglobin * fit*, ~'aUSe was 5^ historical precedent does not make m 1 "ow- II is a parucuiarlv interesting unit of normality, *euAt<Kr*^n*te^ Haldane in a rather small series ("My ^e~\ --l*50uSh this oxoaian quotation may be *4, *-p 3';' ^ngnt suggests that if certain biographical ^ re presented to the laboratory, then normal ranges for ma>' also be computed. This is, in fact, bow ,Ntaii\''-.^ll-Srt reported in this institution, and the 'l.! Jr. CUr. Cntrx. 19:.`. f,, IS73. n. M. icd. p. Much of clinical medicine is now committed to using labora tories for monitoring a patient's condition rather than for diagnostic purposes. 3s there a normal hemoglobin for a neph rotic patient or one with chronic lung disease? Changes in absolute values or trends arc far more cause for concern or rejoicing chan their relationships to statistical or mvthical nor mality. The need for an absolute value may be founded on 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, 1 should like to suggest that we do not need yet another frame of reference with which to assess our patients. Surgical lotensivc Can Lnil, Mourn Sinai Hospital, Sew York, Sew York 10029. U.S.A. Christopher W. Bryan-Brows 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 (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 78.1 Because the 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 ascribable 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 Wales for each year under study.' 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 shown in the table the only statistically significant 1. Office cf Population Centmet uJ Surveys. Classification ot Occupjncn H.M. Stationery Office, 1970. 2. Registrar General. Decennial Supplement England and tt'alcr 1961 kc.;ilional mortality tables. H.M. Stauooery Office. 197 1. }. Registrar General. Statistical Reviews of England and Wales for 1970, 19-;. and 1972: pan i, tables, medical. H.M. Stationery Office. *. Office of Population Censuses aod Surveys Census 1971. Grcai Sntair.. eco nomic activity tables pan in. ICC sample. H.M. Stationery Office. 1 M TOOSSZZZ BFG19756 246 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 only 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 Qephrilts and Dcphrosis (I.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 hsemopoietic tissue. The excess deaths from cancer of the stomach and diseases of the urogenitary system were surprising because vinyl HALE PLASTICS WQIIXEHS: DEATHS PROM ALL CAUSES 1970-72 Cause ofdeaih il.C.D. do.) Obs. (O; Exp. (E) CVE All cancers (140-239) Siomach* (i51 j Liver (155! Lung {1611 Bram {I9tj Lvnphaiiclurioooieuc (200-207) EnJoCT nulr.'me'.ayslic (240-279) Cireulaiorv (390-458) Ischemic ,4 I0--H4; Reipiraiorv (46^-519; Bronchitis (490--1*1 j Digestive (520-511; Liver ,570-573; L'rogtr.narv* (580-629) Accidents fESOO-949) Suicides ..E950-959; All other causes 204 185-9 1-1 24 16-4 1-5 I 1-1 0-9 86 99 3 0 9 5 5 0 1-0 3 15-2 0-2 4 6-2 06 3*5 336 0 10 229 22S-D 10 77 80 0 10 42 544 0 8 14 17 1 0 8 3 3 6 0-8 15 8-1 1-9 24 36-8 0-6 5 11-8 0-4 19 25-1 0-8 All 70* 707-0 10 k.0.05. chloride has not so 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. VCfaen 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,' as well as angiosarcoma of the liver and other liver diseases.4 *In6 7this study the observed numbers of deaths from these causes were not in excess of those expected. Ant- excess mortality from these causes which may be present in P.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 p.v.c. manufacturers also show little indication of an excess risk of lung and brain cancer associated with exposure to vinyl chloride.1 ' Health aod Safety Executive, Employment Medical Advisory Sow, I Chepstow Place, Louden V2 4TF, Office of Population Censuses tad Surveys, Medical Slausua Division, St. Caihcnse House, lOKingswav, London VTC2B 6JP. P- J. Baxtx R A. J- FOX 5. Moose, K. R., Peters, J. M_, Johnson. M. N. Lancet. 1974, u, J9". 6. Thomas, L. B., Popper, H, Bert, ?. D., Seiikoff, t,, Falk, H. tint Engl. J. Mid. 197J.292, 17. 7. Duck,B. tr,, Carter, J. T- Cooohes, E. ). Lancet. 1975, u. 1197 8. Fo, A. J., Collier, P. F. The Mortality Experience of Workers Exposed '.o Vinyl Chloride Moocmer la the Manufacture of Polyvinyl Chionde ia Great Britain (U'cpupUieeL ANGIOSARCOMA OF THE UVER y.-fg;.' Sir,--The reports of hxmangiosarcoma of the Uva pk exposed to vinyl chloride1-7 led us to investigate .t*1*?* acion in Holland. We asked all pathology laboratories throughout the ol1 to allow us to study their cases diagnosed as angiosarc^*^ allied conditions). This yielded information on and timoj* 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 tuubZ lion--a well-known association.1 2* 3Angiosarcomas with 'Thorotrast'10 13 were not considered. 2 other anrir-*8"* 10 11 12 comas originated in the spleen. There were 14 non-vascau! tumours of miscellaneous origin, and in 1 case no tumoufV* seen. Histopachological details will be given elsewhere. Agtjj death of the 8 angiosarcoma patients varied between +6 73. One man (aged 56), who had worked for U zinc-chromate primers under primitive circumstances, hM a seminoma at the end of this period and a malignant tumour of uncertain histogenesis more than 10 yean lug The incidence of liver angiosarcoma is difficult to emlm^y Rein and Huth13 bad 6 cases in 30 079 necropsies. Our 8 ca occurred in a fluctuating population of 10-24 million, with least 40 000 necropsies. Remarkably, none of our 21 patiaui had any traceable contact with vinyl chloride. 7 Vt'e are grateful to all patKolog-.su, surgeons, internists, and g^ert} practitioners who cooperated in compiling the data on the 27 patieau. Factory Inspectorate (DGA), Voorburg, P.B. 69. St. Lucas Hospital. Amsterdam. University of Utrecht. Municipal Hospital, Arnhem, Holland. L. M. DaLOERLT ,ri S. C. Fresi G. Bras F. B. Brosckhorst SELECTTVEIgA DEFICIENCY Sir,--You state.13 that there is no difference in the frequency of sinopulmonary infection in healthy serum-IgA-deficient peo ple and healthy blood-donors. There are two different forms of IgA, one in the serum 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-cells. The IgA produced locally differs from serum 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, 5 think it would be unwise to suggest that IgA deficiency is not associated with recurrent infection unless local secretory IgA activity m pa tients with low-serum-lgA has been assessed. Saint Lftufeftcc`1 Hospital, N'artfci drumwick Stmt, Dublin ?, Ireland. MICHAEL FaR*SlL 1. Let, F. I., Harry, D. S. Lone.!, l97A,i. IM6. 2. final4 MedicalJournal, 1974, j, 590. 3. Bniilh MedicalJournal, 1974, iv, 486 4. Falk, H,, Cretell, J. t_. Heath, C. tt1.. Johnson, M. N-. Kev. M. S J A"mid. Ass. 1974,230, 59. 5 Creech, J. C, Johnson, M. N. J. occup. Mid. 1974, 16, 150. 6. Lange, C. E., Jube, S-. Vclunan, C. Dt. mi. tPjcAr. 1974,99, 1598. 7. Ravier, E-, Diier, J. M., Pialat, J. Archs. Mil. prof. Mid. rrae. 1975, 36. 171. 8. Roth, F. Zentbl. Path. path. Anat. 1955,93,424. <*. Regelson. VC_ Kim, L',, Aspina, J,, Holland, J. F. Cancer, 1968,21, 514. 10. MacMahon, H. G,, Murphy, A. S, Bates, B. I.Am.J. Path. 1947, 23, 585 11. Taluk, H., Sordid,1*'. A. Arch* Path. 1955,60. 493. 12. Rein, F. R., Huth, F. lm.Areh. Arbeittmed. 1975,34, 237. 13. Lancet, 1975, ii, 1291. BFG19757 i