332 Our patient’s joint symptoms were probably related to subtle evidence of steroid-induced avascular necrosis, and in the patients who have arthritis-like symptoms after highdose steroid therapy, careful and repeated radiological examinations should be done. We agree with Dr Goldman, however, that each patient should be evaluated individually before ascribing symptoms simply to steroids, since in these immunosuppressed patients it would be disastrous to miss a septic joint.
This work was supported by research grant C-6516 from the National Cancer Institute, National Institutes of Health. Department of Clinical Investigation and Experimental Therapeutics, Sidney Farber Cancer Center, Boston, Massachusetts 02115, U.S.A.
JACOB J. LOKICH.
METHADONE MAINTENANCE p.
Departments of Medicine and Urology, University of Oregon, Health Sciences Center, Portland, Oregon 97201,
SIR,I am quite surprised that your editorial (Jan. 25, 208) made no reference to E. J. Epstein’s ’Methadone:
the Forlorn Hope’.1 Epstein’s review of the evidence from methadone programmes is vastly more critical than your own. He found that the " striking social benefit " you cite is for the most part a clever statistical artefact. The successrates reported ignored age-specific factors, used misleading indicators of criminal involvement, and were for highly selected populations. Those dropped from the programme were usually not included in its evaluation. Nor does the " concept of narcotic blockade " carry much weight after independent tests demonstrated the continued multi-drug use of those under treatment. Methadone advocates have used a medical rationale to justify a programme of social control-the State now distributes the narcotic-which has had little positive impact on either drug abuse or violent crime. They do not deserve the continued support of leading medical journals. Centre for Studies in Social Policy, 62
Doughty Street,
SANFORD L. WEINER.
London WC1N 2LS.
ARTHRALGIA AFTER HIGH-DOSE STEROIDS
SIR,—This letter concerns Dr Goldman’s comments (Nov. 30, p. 1333) on musculoskeletal disorders following renal transplantation and also to previous correspondence about arthralgia after high-dose intravenous methylprednisolone. We have had recent experience with a particularly instructive case. A 59-year-old White female had a cadaver transplant in August, 1973, preceded four months earlier by bilateral nephrectomy. The pathological diagnosis was arteriolonephrosclerosis
and chronic pyelonephritis. She had no known history of gout, rheumatoid arthritis, or systemic lupus erythematosus. She had two early transplant rejections which were reversed by high-dose steroid therapy, and six months after transplantation she had a creatinine clearance of 60 ml. per minute. She received equine antilymphocyte serum at the time of transplantation, but this was stopped in November, 1973. She had no musculoskeletal symptoms at that point. In May, 1974, while on constant doses of 20 mg. of prednisone per day, acute pain developed in her right knee, right index finger, and right elbow, without physical findings of warmth, redness, or swelling. She had difficulty moving the affected joints; however, determinations of blood-uric acid, rheumatoid
factor, lupus erythematosus preparation, antistreptolysis-0 titre, and serum-complement were all normal. X-ray examinations of the affected joints were normal. In August, 1974, because of a decreased glomerular-filtration rate to 20 ml. per minute, she was given large pulse doses of methylprednisolone as treatment for presumedtransplant rejection. During an intensive course of such therapy with large doses first given daily and then at weekly intervals, she had acute onset of swelling and pain, and an obvious effusion in her right knee. Serum uric acid, complement, antinuclear antibody, D.N.A. antibodies, and L.E. preparations were normal. Joint fluid was aspirated and the uric acid was 8 mg. per 100 ml., the same as in the serum. The joint fluid was light yellow and had normal viscosity at 25°C. White cells in the joint fluid were 44 per c.mm. (75% lymphocytes). No crystals or inclusion bodies were seen. X-ray examination of the knee showed evidence of subcondylar fractures of the femoral condyle.
U.S.A.
LYMPHOCYTES IN SPLEEN IN HODGKIN’S DISEASE
‘
SIR,-We read with interest the paper of Dr Kaur and others (Oct. 5, p. 800) about the relative distribution of T and B lymphocytes in spleen and peripheral blood from patients with Hodgkin’s disease. They found a normal pattern in the peripheral blood, while in the spleens the mean percentage of P.H.A.-responsive cells was significantly higher than that in the non-malignant spleens. The behaviour of blood lymphocytes is at variance with most reported data, and one wonders whether all the findings could be related to the histological variety, in most cases nodular sclerosis. However, we should like to comment on the second point-namely, the spleen findings. We were able to demonstrate 1-3 in the serum of patients with Hodgkin’s disease the presence of IgG cytotoxic antibodies, active on both autochthonous and allogeneic lymphocytes. In peripheral blood a high percentage of lymphocytes exhibit surface IgG, seemingly T lymphocytes coated by the autoantibody.3 More recently,4 we demonstrated that: (a) the IgG cytotoxins can be eluted from peripheral lymphocytes which become normal as regard to surface IgG; and (b) the eluted cytotoxin " spots " a high percentage of lymphocytes passed through a Degalan V 26 column coated with an anti-Ig antibody (i.e., T lymphocytes). Blood lymphocytes from patients with Hodgkin’s disease also show impaired ability to form E-rosettes.6 These data have been confirmed.On the other hand E.A.C.rosette formation in Hodgkin’s disease is normal, suggesting that B lymphocytes are not involved in the disease. Our group had the opportunity of studying spleen and lymph-node cells of a small group of Hodgkin’s patients with regard to P.H.A. transformation, E-rosette and E.A.C.rosette formation, and surface immunoglobulins (sIg), in comparison with peripheral lymphocytes. All mononuclear cells wers obtained by density gradient usingLympho-
prep ’ (Nyegaard, Oslo). Lymphocytes from the spleen
of 5 patients with Hodgkin’s disease in various stages (2 stage 11, 2 stage ill, and 1 stage iv) and with variable involvement of the organ (1 with mixed cellularity, 2 with lymphocyte depletion, and 2 not involved) did not differ significantly from peripheral blood lymphocytes with regard to P.H.A. transformation, sIgG, E, and E.A.C. rosette formation. In every 1. 2. 3. 4.
Summer,
1974.
Grifoni, V., Del Giacco, G. S., Tognella, S. Br. med. J. 1969, iii, 414. Grifoni, V., Del Giacco, G. S., Tognella, S., Manconi, P. E. Lancet, 1971, i, 293. Grifoni, V., Del Giacco, G. S., Manconi, P. E., Tognella, S. ibid. 1972, i, 848. Grifoni, V., Del Giacco, G. S., Manconi, P. E., Tognella, S., Mantovani, G., Turno, R. 2nd Meeting European and African Division, International Society for Haematology, Prague, 1973; p. 122.
Giacco, G. S., Manconi, P. E., Tognella, S., Mantovani, G., Grifoni, V. Fol. Allergol. Immun. clin. 1974, 21, 71. Kaplan, H. S., Bobrove, A. M., Fuks, Z., Strober, S. New Engl. J. Med. 1974, 290, 971.
5. Del 6.
1. Public Interest,
WILLIAM M. BENNETT DAVID STRONG.
This work was supported by research grant C-6516 from the National Cancer Institute, National Institutes of Health. Department of Clinical Investigation and Experimental Therapeutics, Sidney Farber Cancer Center, Boston, Massachusetts 02115, U.S.A.
JACOB J. LOKICH.
METHADONE MAINTENANCE p.
Departments of Medicine and Urology, University of Oregon, Health Sciences Center, Portland, Oregon 97201,
SIR,I am quite surprised that your editorial (Jan. 25, 208) made no reference to E. J. Epstein’s ’Methadone:
the Forlorn Hope’.1 Epstein’s review of the evidence from methadone programmes is vastly more critical than your own. He found that the " striking social benefit " you cite is for the most part a clever statistical artefact. The successrates reported ignored age-specific factors, used misleading indicators of criminal involvement, and were for highly selected populations. Those dropped from the programme were usually not included in its evaluation. Nor does the " concept of narcotic blockade " carry much weight after independent tests demonstrated the continued multi-drug use of those under treatment. Methadone advocates have used a medical rationale to justify a programme of social control-the State now distributes the narcotic-which has had little positive impact on either drug abuse or violent crime. They do not deserve the continued support of leading medical journals. Centre for Studies in Social Policy, 62
Doughty Street,
SANFORD L. WEINER.
London WC1N 2LS.
ARTHRALGIA AFTER HIGH-DOSE STEROIDS
SIR,—This letter concerns Dr Goldman’s comments (Nov. 30, p. 1333) on musculoskeletal disorders following renal transplantation and also to previous correspondence about arthralgia after high-dose intravenous methylprednisolone. We have had recent experience with a particularly instructive case. A 59-year-old White female had a cadaver transplant in August, 1973, preceded four months earlier by bilateral nephrectomy. The pathological diagnosis was arteriolonephrosclerosis
and chronic pyelonephritis. She had no known history of gout, rheumatoid arthritis, or systemic lupus erythematosus. She had two early transplant rejections which were reversed by high-dose steroid therapy, and six months after transplantation she had a creatinine clearance of 60 ml. per minute. She received equine antilymphocyte serum at the time of transplantation, but this was stopped in November, 1973. She had no musculoskeletal symptoms at that point. In May, 1974, while on constant doses of 20 mg. of prednisone per day, acute pain developed in her right knee, right index finger, and right elbow, without physical findings of warmth, redness, or swelling. She had difficulty moving the affected joints; however, determinations of blood-uric acid, rheumatoid
factor, lupus erythematosus preparation, antistreptolysis-0 titre, and serum-complement were all normal. X-ray examinations of the affected joints were normal. In August, 1974, because of a decreased glomerular-filtration rate to 20 ml. per minute, she was given large pulse doses of methylprednisolone as treatment for presumedtransplant rejection. During an intensive course of such therapy with large doses first given daily and then at weekly intervals, she had acute onset of swelling and pain, and an obvious effusion in her right knee. Serum uric acid, complement, antinuclear antibody, D.N.A. antibodies, and L.E. preparations were normal. Joint fluid was aspirated and the uric acid was 8 mg. per 100 ml., the same as in the serum. The joint fluid was light yellow and had normal viscosity at 25°C. White cells in the joint fluid were 44 per c.mm. (75% lymphocytes). No crystals or inclusion bodies were seen. X-ray examination of the knee showed evidence of subcondylar fractures of the femoral condyle.
U.S.A.
LYMPHOCYTES IN SPLEEN IN HODGKIN’S DISEASE
‘
SIR,-We read with interest the paper of Dr Kaur and others (Oct. 5, p. 800) about the relative distribution of T and B lymphocytes in spleen and peripheral blood from patients with Hodgkin’s disease. They found a normal pattern in the peripheral blood, while in the spleens the mean percentage of P.H.A.-responsive cells was significantly higher than that in the non-malignant spleens. The behaviour of blood lymphocytes is at variance with most reported data, and one wonders whether all the findings could be related to the histological variety, in most cases nodular sclerosis. However, we should like to comment on the second point-namely, the spleen findings. We were able to demonstrate 1-3 in the serum of patients with Hodgkin’s disease the presence of IgG cytotoxic antibodies, active on both autochthonous and allogeneic lymphocytes. In peripheral blood a high percentage of lymphocytes exhibit surface IgG, seemingly T lymphocytes coated by the autoantibody.3 More recently,4 we demonstrated that: (a) the IgG cytotoxins can be eluted from peripheral lymphocytes which become normal as regard to surface IgG; and (b) the eluted cytotoxin " spots " a high percentage of lymphocytes passed through a Degalan V 26 column coated with an anti-Ig antibody (i.e., T lymphocytes). Blood lymphocytes from patients with Hodgkin’s disease also show impaired ability to form E-rosettes.6 These data have been confirmed.On the other hand E.A.C.rosette formation in Hodgkin’s disease is normal, suggesting that B lymphocytes are not involved in the disease. Our group had the opportunity of studying spleen and lymph-node cells of a small group of Hodgkin’s patients with regard to P.H.A. transformation, E-rosette and E.A.C.rosette formation, and surface immunoglobulins (sIg), in comparison with peripheral lymphocytes. All mononuclear cells wers obtained by density gradient usingLympho-
prep ’ (Nyegaard, Oslo). Lymphocytes from the spleen
of 5 patients with Hodgkin’s disease in various stages (2 stage 11, 2 stage ill, and 1 stage iv) and with variable involvement of the organ (1 with mixed cellularity, 2 with lymphocyte depletion, and 2 not involved) did not differ significantly from peripheral blood lymphocytes with regard to P.H.A. transformation, sIgG, E, and E.A.C. rosette formation. In every 1. 2. 3. 4.
Summer,
1974.
Grifoni, V., Del Giacco, G. S., Tognella, S. Br. med. J. 1969, iii, 414. Grifoni, V., Del Giacco, G. S., Tognella, S., Manconi, P. E. Lancet, 1971, i, 293. Grifoni, V., Del Giacco, G. S., Manconi, P. E., Tognella, S. ibid. 1972, i, 848. Grifoni, V., Del Giacco, G. S., Manconi, P. E., Tognella, S., Mantovani, G., Turno, R. 2nd Meeting European and African Division, International Society for Haematology, Prague, 1973; p. 122.
Giacco, G. S., Manconi, P. E., Tognella, S., Mantovani, G., Grifoni, V. Fol. Allergol. Immun. clin. 1974, 21, 71. Kaplan, H. S., Bobrove, A. M., Fuks, Z., Strober, S. New Engl. J. Med. 1974, 290, 971.
5. Del 6.
1. Public Interest,
WILLIAM M. BENNETT DAVID STRONG.
