INTRATHECAL CYTARABINE IN MULTIPLE SCLEROSIS

204

prednisolone 5 mg daily, aspirin 600 mg twice daily, and indomethacin suppositories 100 mg at night. In January, 1979, ANA titre remained 1/640; DNA binding was 20 u/ml. IgM rheumatoid factor was still negative. In May 1979, the level of circulating immune complexes (measured by Clqbinding) was very high. In the following month, rheumatoid nodules developed around both elbows and smaller nodules were noted over the extensor aspects of her fingers. Rheumatoid factor was positive. X-ray of hands and feet showed synovial thickening and periarticular erosions. Hairy-cell leukaemia has lately been shown to be a B-cell proliferative disorder.3 We believe that this patient represents example of the association of autoimmunity with another B-cell disorders. M. A. J. CROFTS Department of Hæmatology, J. C. SHARP King’s College Hospital, Denmark Hill, London SE5 9RS

M. V. JOYNER

DIGOXIN AND HORMONE RECEPTORS et al. reported a lower recurrence-rate and abnormal morphology of breast cancer in women receiving "cardiac glycosides (mainly digoxin)," and LeWinn5 summarised other oestrogenic effects of digitalis. We have investigated the suggestion that digoxin interferes with oestrogen receptor (ER) on cytosols from eleven primary human breast carcinomas containing ER (mean 143 fmol/ml cytosol, range 46-304); the in-vitro binding of 3H-oestradiol6 0-9 nmol/1 was unaffected by 10 µmol/l digoxin. In the cytosol from two of these tumours, lower concentrations of digoxin (0.1, 1.0, 10, and 100 nmol/l, 1.0 µmol/l) also failed to compete with the binding of oestrogen to ER. Progesterone receptor (PgR) is another possible site of action of digoxin, especially since progesterone has been reported to bind to cardiac digoxin receptor.7 However, in cytosol from each of seven primary breast tumours containing PgR (mean 327 fmol/ml cytosol, range 92-740), digoxin at two concentrations (1-0 nmol/1 and 10 pnnol/1) did not interfere with the binding of the synthetic progesterone analogue R5020. The higher concentrations of digoxin used were considerably greater than the therapeutic range (0-65-2-60 nmol/1) and it is therefore unlikely that digoxin has any direct action on the binding of oestradiol of progesterone to their cytosol receptors in breast cancer in vivo. These results do not exclude the possibilities that digoxin exerts other direct effects on breast cancer or that one of the other cardiac glycosides competes for ER or PgR.

SIR,-Stenkvist

an

Department of Medicine, Queen Elizabeth Hospital, University of Birmingham, Birmingham B15 2TH and Dudley Road Hospital, Birmingham

D.H. COVE G. A. BARKER

INTRATHECAL CYTARABINE IN MULTIPLE SCLEROSIS

SIR,—There is considerable interest in immunosuppressive in the management of multiple sclerosis (MS)8 and we wish to describe briefly our limited experience with intrathecal cytarabine. This agent has antiviral9 and immunosuppressant qualities--compatible with current notions concerning the possible aetiology of MS-and success has been claimed in the

therapy

3.

Jansen J, Schmit HRE, Van Zwet ThL, Meizer CJLM, Hijman W. Hairy Cell Leukæmia; A B Lymphocytic Disorder. Brit J Hæmat 1979; 42:

21-34. 4. Stenkvist B, Bengtsson E, Eridsson O, Holmquist J, Nordin B, WestmanNaeser S. Cardiac glycosides and breast cancer. Lancet 1979; i; 563. 5. LeWinn EB. Cardiac glycosides and breast cancer. Lancet 1979; i; 1196. 6. Woods KL, Cove DH, Howell A. Predictive classification of human breast carcinomas based on lactalbumin synthesis. Lancet 1977, ii; 14-15. 7. La Bella FS, Bihler I, Ki RS. Nature 1979; 278; 571. 8. Ellison GW, Myers LW. A review of systemic non-specific immunosuppressive treatment of multiple sclerosis. Neurology 1978; 28: 132-39. 9. Lanter CB, Bailey EJ, Lerner M. Assessment of cytosine arabinoside as an antiviral agent in humans. Antimicrob Ag Chemother 1974; 6: 598-602.

of progressive multifocal leucoencephalopathy,10-12 a disorder probably involving similar viral and immunological mechanisms. Since there are theoretical objections to systemic immunosuppression when the disease process is confined to the central nervous system and since intrathecal cytarabine has been used extensively and with safety in childhood leukxmia it seemed reasonable to use the intrathecal route. The project was approved by the ethics committee of University College Hospital and Medical School. Five patients with unequivocal disseminated sclerosis undergoing acute disabling exacerbations were invited to participate in a pilot study. One patient was subsequently rejected because we felt that the extent of his disease impaired his ability to understand the nature of the trial; the remainder gave their consent after detailed discussion. The regimen consisted of four intrathecal injections of 40 mg cytarabine in water 5 days apart. Patients were closely observed and progress was recorded; they were seen every week by an independent assessor. Three of the four patients failed to complete the course of treatment: two had signs of meningeal irritation and evidence of further neurological deterioration and the other experienced no meningism but continued to deteriorate. Only one patient completed the course without disturbance, but the pattern of the exacerbation showed no dramatic improvement. Following withdrawal from the trial, two of the three patients who had continued to deteriorate neurologically improved when given steroids. Two patients have been followed up for over a year and have experienced further relapses similar to the pre-treatment pattern of their disease. This pilot study was designed to determine the safety and possible efficacy of direct immunosuppression of the central nervous system in patients with MS. We report our disappointing experience in case others are considering a similar approach. While some of the meningeal reactions might be similar to those seen in patients with MS after diagnostic lumbar puncture, our clinical impression discourages us from offering this treatment to other patients. MARTIN GORE Department of Neurology, ROBERT BUCKMAN University College Hospital, London WC1 GERALD STERN treatment

HISTIOCYTIC MEDULLARY RETICULOSIS

SIR,-Schumacher and Stassl suggest that all cases of histiocytic medullary reticulosis (HMR) should be carefully investigated for viral, bacterial, or parasitic infections and carcinoma. They describe a case of apparent HMR associated with gastric carcinoma, and cases of HMR associated with viral infection2,3 and, possibly, with parasitic infection’ have been described. We support Schumacher and Stass’s suggestion. Two patients seen by us presented with an HMR-like illness due to a bacterial infection. Both had pyrexia, lymphadenopathy, hepatosplenomegaly, and pancytopenia. On bone-marrow aspiration there were sheets of bizarre, atypical histiocytes, many of which showed erythrocyte, granulocytic, and platelet phagocytosis. Subsequently both cases were shown to have typhoid fever and recovered fully on antibiotic treat10. Bauer

WR, Turel AP, Johnson JP. Progressive multifocal leucoencephaloand cytarabine: remission with treatment. JAMA 1973; 226:

pathy

174-76. 11. Marriott PJ, O’Brien MD, Mackenzie ICK, Janota IJ. "Progressive mulufocal lencoencephalopathy: remission with cytarabine". J Neurol Neurosurg Psychiat 1975; 38: 205-09. 12. Wiltshaw E, Buckman R. Progressive multifocal lencoencephalopathy successfully treated with cytosine arabinoside. Br J Hœmatol 1976, 34: 153-55. 1. Schumacher HR, Stass SA. Lancet 1979; i: 158-59. 2. Chandra P, Chaudhery SA, Rosner F, Kagan M. Transient histiocytosis with striking phagocytosis of platelets, leukocytes and erythrocytes. Arch In-

tern Med 1975; 135: 989-91. 3. Risdall R, McKenna R, Kriuit W, Nesbitt M, Brunning R. Virus associated hemophagocytic syndrome. Blood 1978; 52: suppl i, 272 (abstr). 4. Serck-Hanssen A, Purchit GP. Histiocytic medullary reticulosis. Br J Cancer

1968, 22: 506-16.