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ARCUS SENILIS AND ALCOHOL INTAKE

SIR,-Dr Castelli and his colleagues (July 23, p. 153) reporta strongly positive association between alcohol consumptionand high-density-lipoprotein cholesterol in their multicentrestudy. They report a more modest positive association betweenalcohol and triglycerides, and a negative association with low-density-lipoprotein cholesterol.These results interest us because of our observations on the

positive association between alcohol intake and arcus senilis.In 1970’ we reported on the connection between arcus senilisand a variety of attributes and risk factors in coronary pa-tients. These included age, lifetime smoking, serum-choles-terol, total serum-lipids, diastolic blood-pressure, alcohol con-sumption, glucose tolerance, obesity, fat folds, exercise

experience, haematocrit, uric acid, and serum-magnesium.An expected, positive correlation between intensity of arcus

and age was noted and a negative association with obesity wasexplicable on the grounds that older patients were lighter. Apositive association between lifetime alcohol consumption andintensity of arcus was significant (P<0-01) in 534 subjects. Noassociation was noted with the other attributes studied, includ-ing serum-cholesterol and total serum-lipids.

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We concluded that the relationship between arcus and alco-hol merited further study. Our findings and the report from DrCastelli and his colleagues may be of interest in postulating arole for alcohol, high-density-lipoprotein cholesterol, and/ortriglycerides in the genesis of arcus senilis and particularly ofarcus in its precocious from. There is certainly no substantialevidence in the literature to support the common view that

abnormally raised low-density-lipoprotein cholesterol is xtio-logically associated with precocious arcus.

The Sisters of CharitySt. Vincent’s Hospital,Elm Park, Dublin 4

RISTEARD MULCAHYNOEL HICKEYBRIAN MAURER

LEVAMISOLE-INDUCED ALLERGY

SIR,-Dr Christiansen and his colleagues (May 21, p. 1111)described two patients who had febrile reactions to levamisole.In a similar case our patient had reaginic antibodies (type I

allergy) to levamisole.A 69-year-old woman with Wegener’s granulomatosis (lym-

phomatoid type) diagnosed by chest X-ray and lung biopsy,had recurrent pulmonary and urinary-tract infections. On twooccasions Diplococcus pneumonice and Escherichia coli werecultured from her blood. The patient’s cellular immunity wasimpaired, as shown by negative skin tests for delayed hyper-sensitivity low in-vivo response of lymphocytes to mitogens.To improve cellular immunity levamisole, 50 mg three times

daily for three days a week, was started. During the secondweek, after she had had two tablets the patient had chills,fever, and confusion. Withdrawal of the drug resulted in reso-

MAST-CELL SENSITISING ANTIBODY IN SERUM OF PATIENT

TREATED WITH LEVAMISOLE

*200 mast cells were evaluated in each experiment.

1. Hickey, N., Maurer, B., Mulcahy, R. Br. Heart J. 1970, 72, 449.

lution of all symptoms with 24 h. 14 days later a challenge of50 mg levamisole was given. 3 h later the patient had severechills and fever and became unconscious. Clinical and labora-

tory investigations, including urine and blood cultures, failedto reveal any cause; the symptoms resolved within 3 days.We looked for reaginic antibodies in the patient’s serum by

the indirect mast-cell degranulation test.1,2 Serum was testedfor ability to degranulate rat mast cells in the presence oflevamisole. As shown in the table, serum before treatment withlevamisole (June 25) was negative while serum after treatment(Nov. 16) caused degranulation. Incubation of active serum at56&deg;C for 4 h rendered the serum inactive, which suggests thepresence of antibody of the IgE type. 3

These clinical and laboratory findings suggest that our pa-tient had a type-I allergy to levamisole. Levamisole is used inpatients with impaired cellular immune response such as

autoimmune and neoplastic diseases. Fever and chills are notuncommon in these clinical states, and allergy to levamisolecould be a precipitating factor.

University Department of Medicine B,Ichilov Medical Center

and Department of Human Microbiology,Tel-Aviv University Medical School,Tel-Aviv, Israel

ISRAEL YUSTNURITH VARDINONEDITH FIERSTETERLEON A. AVRAMOV

CYCLOPHOSPHAMIDE AND MALIGNANCY

SIR,-The correspondence in your columns (June 18, p.1306, July 23, p. 196) provides an opportunity for drawingattention to a change in prescribing recommendations forcyclophosphamide (’Endoxana’). Although present prescribinginformation does identify possible complications such as sub-sequent malignancies, particularly in relation to use in

non-malignant conditions, the latest data indicate that it is

appropriate to strengthen this warning. Therefore all futureprescribing information for endoxana will omit reference touse in non-malignant disease other than in life-threateningsituations. Naturally further details will be available from thisCompany if required, but it is hoped that this change will serveto increase awareness of possible secondary hazards.

WB Pharmaceuticals Limited,PO Box 23, Bracknell, Berkshire RG12 4YS.

P. A. KNOWLSONMedical Director

ZINC AND DIALYSIS AN&AElig;MIA

SIR,-Dr Stewart and his colleagues (July 16, p. 139) areright to draw attention to the fact that dialysis anaemia is acomplex multifactorial problem. They found that dialysingagainst zinc concentrations of about 5 mol/1 initially, fallingto 1.5 5 [jLmol/t a year later, did not lead to anaemia, and theywonder whether we were somewhat hasty in ascribing ourproblems of dialysis anaemia to zinc concentrations which werenot markedly greater than theirs.We had two groups of dialysis patients being dialysed

against the same mains water. Thus any toxic agent present inmains water should have caused problems in both units.Anaemia occurred in the satellite unit only. The anaemia "epi-demic" coincided with the introduction of a galvanised-ironwater softener to the satellite unit, and occurred in associationwith the elution of zinc from the new water softener.4 The gal-vanised iron may have contained a metallic impurity whichwas eluted along with zinc and which we failed to detect. It isalso possible that zinc acted as a cofactor potentiating anaemiacaused by chloramines or some other impurity in the mainswater. It is however difficult in the face of the association we

1. Vardinon, N., Levanon, M., Schwartz, J. Acta allergol. 1967, 22, 28.2. Schwartz, J., Eyquem, A., Vardinon, N. Immun. Commun. 1975, 4, 243.3. Ishizaka, K., Ishizaka, T., Menzel, A. I. O. J. Immun. 1967, 99, 610.4. Patrie, J. J. B., Row, P. G. Lancet, 1977, i, 1178.

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noted to regard zinc as anything other than an importantagent in causing anaemia.

Zinc concentrations in our dialysate would have been attheir highest in February when the softener was installed.However, we did not measure the concentration until lateApril. Thus we experienced anaemia problems when dialysingpatients against dialysate zinc concentrations which were in-itially considerably more than 5 p.mol/1, falling to about 5mol/1 in ten weeks. Dr Stewart and his colleagues experiencedno problems dialysing patients against zinc concentrationswhich were initially around 5 jmol/1 and which fell to 1.5mol/1 over one year. Both observations would be consistentwith (for example) a hypothesis that anaemia problems can beinitiated by zinc concentrations of about 15 p.mol/1 and sus-tained by concentrations around 5 mol/1.

In Gallery’s home-dialysis patient2 and the two home-dia-lysis patients reported by us, severe anaemia problems developedwhen the patients were being dialysed against zinc concentra-tions of 20-50 p.mol/1. Thus we believe that zinc can be toxic.Because we did not measure zinc concentrations at the start ofour anaemia epidemic, we are unable to set a precise limit tothe toxic level, but we do not feel that the recommended con-centration3 of 76 &micro;mol/l (5 p.p.m.) is acceptable. Concentrationsof 2-3 p.mol/1 seem to be safe but concentrations of more than20 mol/1 are probably harmful.Princess Alexandra Hospital,Ipswich Road, Woolloongabba,Queensland 4102, Australia

G. Row

J. J. B. PETRIE

FALSE-POSITIVE MECONIUM SCREEN

SiR,&mdash;The BM meconium test is a useful screening test forcystic fibrosis. However, we have had false-positive results intwo babies caused by the use of rectal glycerin suppositories.The babies presented with signs suggestive of intestinalobstruction possibly due to meconium ileus, and glycerin sup-positories were inserted to speed the passage of meconium sothat the BM test could be done to help confirm the diagnosis.The tests were positive but the babies were subsequentlyshown not to have cystic fibrosis, and we found that the gly-cerin suppositories themselves produce the typical blue colouron the test strip. The manufacturers (Boehringer, Mannheim)have confirmed our findings and will add to their instructionleaflet a note that glycerin suppositories may cause a false-positive BM test.

Department of P&aelig;diatrics,Southmead General Hospital,Bristol BS10 5NB

H. M. BERGERS. J. REYNOLDSK. H. LEE

ASPIRIN AND HEARING IMPAIRMENT

SIR,-We have had an inquiry about a case of prolongeddeafness associated with aspirin use in a recent report of ours.’On reviewing the original record we learned that this patienthad had hearing impairment before receiving aspirin. Whileaspirin apparently increased the degree of hearing impairment,the drug should probably not be implicated in the productionof what may have been permanent deafness in this patient.Boston Collaborative Drug Surveillance Program,Boston University Medical Center,Waltham, Massachusetts 02154, U.S.A.

JANE PORTERHERSHEL JICK

2. Gallery, E. D. M., Blomfield, J., Dixon, S. R. Br. med. J. 1972, iv, 331.3. Comty, C., Luehmann, D, Water, R., Shapiro, F. Trans. Am. Soc. artif.

intern. Organs, 1974, 20, 189.1. Porter, J., Jick, H. Lancet, 1977, i, 587.

CALCIUM CARBONATE AND I.U.D. PREGNANCIES

SIR,-Your editorial entitled Which l.U.D.1 prompts us tocomment on our findings of a very positive correlation betweencalcium-carbonate coatings on copper-7 intrauterine devices(t.u.D.s) and pregnancy. Copper i.u.D.s quite often becomecoated with calcium carbonate after several months of use.2-4

In our first quantitative study,2 5 of the 23 copper-7s camefrom pregnant women, and all 5 had extensive calcium-car-bonate deposits (see table). 3 other Lu.D.s removed because the

CALCIUM-CARBONATE DEPOSITS ON COPPER-7 l.U.D. CORROSIONLAYERS

*Calcium content by atomic absorption; carbonate evident fromeffervescence, but small amounts of other anions could be present too.

3 other l.V.D.S removed from pregnant women also had extensive cal-cium-carbonate deposits. Calcium content was not determined for 5 ofthe first 23 samples.

woman seemed pregnant also had extensive calcium-carbonatedeposits covering the copper wire. We have examined manyI.U.D.s removed for other reasons, and in about half of thesedevices no calcium carbonate was found. Where calcium-car-bonate had been deposited on devices removed for reasonsother than pregnancy it was usually localised and should nothave greatly affected the dissolution-rate of the copper. 4 or 5of the devices removed for reasons other than pregnancy didhave extensive calcium-carbonate layers. This is not surprisingbecause the plastic device even without any copper is an

effective contraceptives and pregnancy-exposure risks do vary.The presence of extensive deposits on all 8 I.U.D.S removed

from pregnant women does not prove that the layer contri-buted to the pregnancy, but it is certainly suggestive. The coat-ing should appreciably slow the release-rate of copper. Onestudy which attempted to determine copper loss includedi.u.D.s removed from 2 pregnant women, and in both thesedevices the rate of copper loss was appreciably lower thanaverage. However, variations in the composition of the corro-sion layers2 and in the weight of the copper in the devices’make such estimates only semiquantitative.

Inert I.U.D.S also show calcium salt deposits,? so any I.U.D.which releases an active agent should have its efficacy limitedby the build-up of calcium salts. As you noted’ women carry-

1. Lancet, 1977, i, 1239.2. Lewis, K. M., Archer, R. D., Ginsberg, A. P., Rosencwaig, A. Contraception,

1977, 15, 93.3. Gosden, C., Ross, A., Loudon, N. B. Br. med. J. 1977, i, 202.4. VanEyck, J., Lagasse, A., Thiery, M. Contraception, 1976, 13, 65.5. Zipper, J., Medel, M., Pastene, L., Rivera, M., Torres, L., Osorio, A., Tos-

canini, C. ibid. p. 7.6. Zielske, F., Koch, F., Badura, R., Ladeburg, H. ibid. 1974, 10, 651.7. Engineer, A. D., Dasgupta, P. R., Kar, A. B. Am. J. Obstet. Gynec. 1970,

106, 315.