- Email: [email protected]
POPULATION POLICY
1023
occasions. She was transfused with two units of fresh blood and started on prednisone 60 mg. daily. This was
gradually reduced over the next four weeks, as the bloodpicture improved, and was eventually stopped. 10 days after admission she developed microscopic haematuria with occasional casts; her electrolytes remained normal, but the blood-urea rose to 45 mg. per 100 ml., with an endogenous-creatinine clearance of 42 ml. per minute. The intravenous pyelogram was normal. A renal-biopsy specimen was " indicative of a tubular or tubulo-interstitial lesion of temporary character-possibly of toxic next fortnight the haematuria cleared and creatinine clearance rose to 71 ml. per minute. Serological studies 22 weeks after the onset of the acute toxic reaction showed a Rose-Waaler titre of 1/128 and a weakly positive immunofluorescence test for A.N.F. That phenylbutazone can induce L.E. cell phenomenon1 and that 14% of patients with rheumatoid arthritis have positive A.N.F.2 are well known. An increasing number of drugs are now known to be capable of inducing a systemic-
origin ". Over the
It seems that they The first is by virtue of peculiar pharmacological properties-as with hydrallazine,3 isoniazid, hydantoin anticonvulsants,4 and procainamide.1 The other group, which includes sulphonamides,6 methyldopa, and oral contraceptives,8 is supposed to elicit allergic reactions which in turn bring about the syndrome. While we cannot exclude the possibility that the patient described here had a form of S.L.E. presenting initially with a rheumatoid type of arthropathy, this explanation is not favoured for two reasons: (1) there was no evidence of renal involvement by any of the distinctive lesions9 despite prolonged haematuria, and (2) the strong initial seropositivity for the rheumatoid factor. We postulate that, as a result of an allergic reaction, phenylbutazone induced 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 thus be due to toxic renal tubular necrosis, and this interpretation is consistent with the biopsy findings.
lupus-erythematosus-like syndrome. can
do
so
in
one
of
two
ways.
Royal Victoria Infirmary, Newcastle upon Tyne.
N. FARID J. ANDERSON.
NEPHROTIC SYNDROME WITH LYMPHOMA
SiR,-.In regard to the letter by Dr. Muggia and Professor Ultmann (April 17, p. 805), we have reported another cause of reversible nephrotic syndrome in malignant lymphomas-compression of the inferior vena cava and the renal veins by the tumour mass.11 Distant localisations sometimes regress when a lymphomatous mass is subjected to local radiotherapy, and this could explain the clinical evolution in the 2 patients reported by Muggia and Ultmann. Hematology Research Laboratory, Department of Medicine, Massachusetts General Hospital, Boston, Mass. 02114. 1. 2.
WILLY F. PIESSENS.
Ogryzle, M. A. Can. med. Ass. J. 1956, 75, 980. 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 SiR,-The concept, mentioned by some of your correspondents, that you can obtain a well-balanced society simply by matching the birth-rate to the present death-rate is an over-simplification of the problem, for it takes no account of the changing mortality trends in the past eighty years. Before any reduction in the future birth-rate below the present level is encouraged, one should try to predict the impact that this would have on all aspects of our society by consulting the life table published in the Registrar General’s Quarterly Return for the June Quarter, 1969, no. 482, which has been constructed based on the mortality in the three years 1966 to 1968. St. George’s Hospital, London S.W.17.
PETER H. MILLARD.
E.B. VIRUS ANTIBODY IN SYSTEMIC LUPUS ERYTHEMATOSUS SIR,-Dr. Newell and Dr. Stevens (March 27, p. 652) point out that Dalldorf et al.1 reported the presence of precipitating antibody to Epstein-Barr virus (E.B.V.) in cases of systemic lupus erythematosus before our note on the detection of raised E.B.v. antibodies in this condition by the immunofluorescence test.2 I would like to take this opportunity to acknowledge this earlier report. 6 of 21 sera from patients with systemic lupus erythematosus had precipitating antibody; however, no case data or immunofluorescent-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 the results of immunofluorescence tests. Dr. Newell and Dr. Stevens rightly indicate the difficulties encountered in immunofluorescent assays of serum containing antinuclear antibody (A.N.A.). With our EB3 cells as well as with the " virus-free " Raji line, diffuse, reticular, and peripheral patterns have been observed in the presence of low dilutions of antinuclear antibody. The reticular network persists the longest. These patterns involved the majority of the cells and contrasted with the homogeneous cellular fluorescence of E.B.V., which involved only 1-5% of the cells. In low serum dilutions (1/5-1/10) the presence of A.N.A. made recognition of E.B.v.-specific fluorescence difficult or impossible, but at dilutions of 160 or higher, which we have considered significantly elevated for E.B.v. antibody, the A.N.A. effect had disappeared except for occasional sera producing a very faint reticular pattern in higher dilutions. While we have been concerned with the specificity of the E.B.v. antibody on this basis, we have found no correlation at all between elevated E.B.v.-antibody titres and the titres of antinuclear antibody by convenventional methods. The absorption of one serum with thymus nucleoprotein removed the antinuclear antibody but not E.B.v. antibody. In accord with other work,3,4 we have also found raised titres to rubella, measles, and parainfluenza viruses in some sera from systemic-lupus patients as compared to, controls. For these antibodies there is growing evidence of specificity.44 A fuller report of our observations is being published. We agree that caution in interpreting results in the presence of antinuclear antibody is well 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. 1. Evans, A.
occasions. She was transfused with two units of fresh blood and started on prednisone 60 mg. daily. This was
gradually reduced over the next four weeks, as the bloodpicture improved, and was eventually stopped. 10 days after admission she developed microscopic haematuria with occasional casts; her electrolytes remained normal, but the blood-urea rose to 45 mg. per 100 ml., with an endogenous-creatinine clearance of 42 ml. per minute. The intravenous pyelogram was normal. A renal-biopsy specimen was " indicative of a tubular or tubulo-interstitial lesion of temporary character-possibly of toxic next fortnight the haematuria cleared and creatinine clearance rose to 71 ml. per minute. Serological studies 22 weeks after the onset of the acute toxic reaction showed a Rose-Waaler titre of 1/128 and a weakly positive immunofluorescence test for A.N.F. That phenylbutazone can induce L.E. cell phenomenon1 and that 14% of patients with rheumatoid arthritis have positive A.N.F.2 are well known. An increasing number of drugs are now known to be capable of inducing a systemic-
origin ". Over the
It seems that they The first is by virtue of peculiar pharmacological properties-as with hydrallazine,3 isoniazid, hydantoin anticonvulsants,4 and procainamide.1 The other group, which includes sulphonamides,6 methyldopa, and oral contraceptives,8 is supposed to elicit allergic reactions which in turn bring about the syndrome. While we cannot exclude the possibility that the patient described here had a form of S.L.E. presenting initially with a rheumatoid type of arthropathy, this explanation is not favoured for two reasons: (1) there was no evidence of renal involvement by any of the distinctive lesions9 despite prolonged haematuria, and (2) the strong initial seropositivity for the rheumatoid factor. We postulate that, as a result of an allergic reaction, phenylbutazone induced 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 thus be due to toxic renal tubular necrosis, and this interpretation is consistent with the biopsy findings.
lupus-erythematosus-like syndrome. can
do
so
in
one
of
two
ways.
Royal Victoria Infirmary, Newcastle upon Tyne.
N. FARID J. ANDERSON.
NEPHROTIC SYNDROME WITH LYMPHOMA
SiR,-.In regard to the letter by Dr. Muggia and Professor Ultmann (April 17, p. 805), we have reported another cause of reversible nephrotic syndrome in malignant lymphomas-compression of the inferior vena cava and the renal veins by the tumour mass.11 Distant localisations sometimes regress when a lymphomatous mass is subjected to local radiotherapy, and this could explain the clinical evolution in the 2 patients reported by Muggia and Ultmann. Hematology Research Laboratory, Department of Medicine, Massachusetts General Hospital, Boston, Mass. 02114. 1. 2.
WILLY F. PIESSENS.
Ogryzle, M. A. Can. med. Ass. J. 1956, 75, 980. 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 SiR,-The concept, mentioned by some of your correspondents, that you can obtain a well-balanced society simply by matching the birth-rate to the present death-rate is an over-simplification of the problem, for it takes no account of the changing mortality trends in the past eighty years. Before any reduction in the future birth-rate below the present level is encouraged, one should try to predict the impact that this would have on all aspects of our society by consulting the life table published in the Registrar General’s Quarterly Return for the June Quarter, 1969, no. 482, which has been constructed based on the mortality in the three years 1966 to 1968. St. George’s Hospital, London S.W.17.
PETER H. MILLARD.
E.B. VIRUS ANTIBODY IN SYSTEMIC LUPUS ERYTHEMATOSUS SIR,-Dr. Newell and Dr. Stevens (March 27, p. 652) point out that Dalldorf et al.1 reported the presence of precipitating antibody to Epstein-Barr virus (E.B.V.) in cases of systemic lupus erythematosus before our note on the detection of raised E.B.v. antibodies in this condition by the immunofluorescence test.2 I would like to take this opportunity to acknowledge this earlier report. 6 of 21 sera from patients with systemic lupus erythematosus had precipitating antibody; however, no case data or immunofluorescent-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 the results of immunofluorescence tests. Dr. Newell and Dr. Stevens rightly indicate the difficulties encountered in immunofluorescent assays of serum containing antinuclear antibody (A.N.A.). With our EB3 cells as well as with the " virus-free " Raji line, diffuse, reticular, and peripheral patterns have been observed in the presence of low dilutions of antinuclear antibody. The reticular network persists the longest. These patterns involved the majority of the cells and contrasted with the homogeneous cellular fluorescence of E.B.V., which involved only 1-5% of the cells. In low serum dilutions (1/5-1/10) the presence of A.N.A. made recognition of E.B.v.-specific fluorescence difficult or impossible, but at dilutions of 160 or higher, which we have considered significantly elevated for E.B.v. antibody, the A.N.A. effect had disappeared except for occasional sera producing a very faint reticular pattern in higher dilutions. While we have been concerned with the specificity of the E.B.v. antibody on this basis, we have found no correlation at all between elevated E.B.v.-antibody titres and the titres of antinuclear antibody by convenventional methods. The absorption of one serum with thymus nucleoprotein removed the antinuclear antibody but not E.B.v. antibody. In accord with other work,3,4 we have also found raised titres to rubella, measles, and parainfluenza viruses in some sera from systemic-lupus patients as compared to, controls. For these antibodies there is growing evidence of specificity.44 A fuller report of our observations is being published. We agree that caution in interpreting results in the presence of antinuclear antibody is well 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. 1. Evans, A.