1023

occasions. She was transfused with two units of freshblood and started on prednisone 60 mg. daily. This was

gradually reduced over the next four weeks, as the blood-picture improved, and was eventually stopped. 10 daysafter admission she developed microscopic haematuria

with occasional casts; her electrolytes remained normal,but the blood-urea rose to 45 mg. per 100 ml., with anendogenous-creatinine clearance of 42 ml. per minute.The intravenous pyelogram was normal. A renal-biopsyspecimen was " indicative of a tubular or tubulo-inter-stitial lesion of temporary character-possibly of toxicorigin ". Over the next fortnight the haematuria clearedand creatinine clearance rose to 71 ml. per minute. Sero-

logical studies 22 weeks after the onset of the acute toxicreaction showed a Rose-Waaler titre of 1/128 and a weaklypositive immunofluorescence test for A.N.F.That phenylbutazone can induce L.E. cell phenomenon 1

and that 14% of patients with rheumatoid arthritis havepositive A.N.F.2 are well known. An increasing number ofdrugs are now known to be capable of inducing a systemic-lupus-erythematosus-like syndrome. It seems that theycan do so in one of two ways. The first is by virtue ofpeculiar pharmacological properties-as with hydralla-zine,3 isoniazid, hydantoin anticonvulsants,4 and pro-cainamide.1 The other group, which includes sulphon-amides,6 methyldopa, and oral contraceptives,8 is sup-posed to elicit allergic reactions which in turn bring aboutthe syndrome.While we cannot exclude the possibility that the patient

described here had a form of S.L.E. presenting initiallywith a rheumatoid type of arthropathy, this explanationis not favoured for two reasons: (1) there was no evidenceof renal involvement by any of the distinctive lesions 9

despite prolonged haematuria, and (2) the strong initial

seropositivity for the rheumatoid factor. We postulatethat, as a result of an allergic reaction, phenylbutazoneinduced an s.L.E.-like syndrome in a predisposed female-in these drug-induced syndromes renal involvement is

quite rare." The ha:maturia in this patient would thusbe due to toxic renal tubular necrosis, and this interpre-tation is consistent with the biopsy findings.

N. FARID

J. ANDERSON.Royal Victoria Infirmary,Newcastle upon Tyne.

NEPHROTIC SYNDROME WITH LYMPHOMA

WILLY F. PIESSENS.

Hematology Research Laboratory,Department of Medicine,

Massachusetts General Hospital,Boston, Mass. 02114.

SiR,-.In regard to the letter by Dr. Muggia and Pro-fessor Ultmann (April 17, p. 805), we have reported anothercause of reversible nephrotic syndrome in malignantlymphomas-compression of the inferior vena cava andthe renal veins by the tumour mass.11 Distant localisationssometimes regress when a lymphomatous mass is sub-

jected to local radiotherapy, and this could explain theclinical evolution in the 2 patients reported by Muggiaand Ultmann.

1. Ogryzle, M. A. Can. med. Ass. J. 1956, 75, 980.2. Weir, D. M., Holborow, E. J., Johnson, G. D. Br. med. J. 1961, i,

933.3. Alarcón-Segovia, D., Wakin, K. G., Worthington, J. W., Ward,

L. E. Medicine, Baltimore, 1967, 46, 1.4. Lee, S. L., Rivero, I., Siegal, M. Archs intern. Med. 1966, 117, 620.5. Ladd, A. T. New Engl. J. Med. 1962, 267, 1357.6. Gold, S. Lancet, 1951, i, 268.7. Sherman, J. D., Love, D. E., Harrington, J. F. Archs intern. Med.

1967, 120, 321.8. Scheicher, E. M. Lancet, 1968, i, 821.9. Soffer, L. J., Southren, A. L., Weiner, H. E., Wolf, R. L. Ann.

intern. Med. 1961, 54, 215.10. Alarcón-Segovia, D. Proc. Staff Meet. Mayo Clin. 1969, 44, 664.11. Piessens, W. F., Zeicher, M. Cancer, 1970, 25, 880.

POPULATION POLICY

PETER H. MILLARD.St. George’s Hospital,

London S.W.17.

SiR,-The concept, mentioned by some of your corre-spondents, that you can obtain a well-balanced societysimply by matching the birth-rate to the present death-rateis an over-simplification of the problem, for it takes noaccount of the changing mortality trends in the past eightyyears. Before any reduction in the future birth-rate belowthe present level is encouraged, one should try to predictthe impact that this would have on all aspects of our societyby consulting the life table published in the RegistrarGeneral’s Quarterly Return for the June Quarter, 1969,no. 482, which has been constructed based on the mortalityin the three years 1966 to 1968.

E.B. VIRUS ANTIBODY IN SYSTEMIC LUPUSERYTHEMATOSUS

SIR,-Dr. Newell and Dr. Stevens (March 27, p. 652)point out that Dalldorf et al.1 reported the presence ofprecipitating antibody to Epstein-Barr virus (E.B.V.) incases of systemic lupus erythematosus before our note onthe detection of raised E.B.v. antibodies in this conditionby the immunofluorescence test.2 I would like to take thisopportunity to acknowledge this earlier report. 6 of 21sera from patients with systemic lupus erythematosus hadprecipitating antibody; however, no case data or immuno-fluorescent-antibody titres in these patients were given.Actually, our Yale group participated in the investigation,as indicated under methods, and a fuller report under

joint authorship is in preparation which includes theresults of immunofluorescence tests.

Dr. Newell and Dr. Stevens rightly indicate the diffi-culties encountered in immunofluorescent assays ofserum containing antinuclear antibody (A.N.A.). Withour EB3 cells as well as with the " virus-free " Raji line,diffuse, reticular, and peripheral patterns have beenobserved in the presence of low dilutions of antinuclearantibody. The reticular network persists the longest.These patterns involved the majority of the cells andcontrasted with the homogeneous cellular fluorescence ofE.B.V., which involved only 1-5% of the cells. In lowserum dilutions (1/5-1/10) the presence of A.N.A. maderecognition of E.B.v.-specific fluorescence difficult or

impossible, but at dilutions of 160 or higher, which wehave considered significantly elevated for E.B.v. antibody,the A.N.A. effect had disappeared except for occasionalsera producing a very faint reticular pattern in higherdilutions. While we have been concerned with the speci-ficity of the E.B.v. antibody on this basis, we have foundno correlation at all between elevated E.B.v.-antibodytitres and the titres of antinuclear antibody by conven-ventional methods. The absorption of one serum withthymus nucleoprotein removed the antinuclear antibodybut not E.B.v. antibody.

In accord with other work,3,4 we have also found raisedtitres to rubella, measles, and parainfluenza viruses insome sera from systemic-lupus patients as compared to,controls. For these antibodies there is growing evidenceof specificity.4 4 A fuller report of our observations is

being published. We agree that caution in interpretingresults in the presence of antinuclear antibody is well

1. Evans, A. S., Rothfield, N., Niederman, J. C. Lancet, Jan. 23,1971, p. 167.

2. Dalldorf, G., Carvalho, R. P. S., Jamra, M., Frost, P., Ehrlich, D.,Marigo, C. J. Am. med. Ass. 1969, 208, 1365.

3. Hurd, E. R., Dowdle, W., Casey, H., Ziff, M. Arthritis Rheum.1970, 13, 324.

4. Hollinger, F. B., Sharp, J. T., Lidsky, M. D., Rawls, W. E. ibid.1971, 14, 1.