453 2. Sanderson BJ, Dempsey JL, Morley AA. Mutations m human lymphocytes. Effect of
X- and UV-irradiation. Mut Res 1984; 140: 223-27. 3. Dempsey JL, Seshadn RS, Morley AA. Increased mutation frequency following treatment with cancer chemotherapy. Cancer Res 1985; 45: 2873-77. 4. Goldie JH, Coldman AJ. Genetic instability in the development of drug resistance. Sem Oncol 1985; 12: 222-30. 5. Riordan JR, Deuchars K, Kartner N, et al. Amplification of P-glycoprotein genes in multidrug-resistant mammalian cell lines. Nature 1985; 316: 817-19. 6. Schimke RT, Hill A, Johnson RN. Methotrexate resistance and gene amplification: an experimental model for the generation of cellular heterogeneity. Br J Cancer 1985; 51: 459-65. 7. Carman MD, Schomagel JH, Rivest RS, et al. Resistance to methotrexate due to gene amplification m a patient with acute leukaemia. J Clin Oncol 1984; 2: 16-20. 8. Champlin R, Gale RP, Elashoff R, et al. Prolonged survival in acute myelogenous leukaemia without maintenance therapy. Lancet 1984; i: 894-96.
TOTAL LYMPHOID IRRADIATION IN MULTIPLE SCLEROSIS
SIR,-In multiple sclerosis (MS) patients undergoing total
lymphoid irradiation (TLI)’ peripheral blood (PB) T cell subsets and B cells should be monitored. The T-suppressor (OKT8)/Thelper (OKT4) cell ratio and the percentage of Fcy cells seem to be useful in evaluating the immunoregulatory effect of a standardised radiation treatment in individuals, as demonstrated here in a 37-year-old woman with MS. The patient experienced an abrupt onset of difficulties to maintain balance on walking at the age of 32, and, 2 years later, progressive muscle weakness in both legs, gradual deterioration in writing, and numbness in the left half of her face. Abnormal neurological findings included unstable gait of broader base, Hoffmann’s and Babinski’s signs bilaterally, and dysmetria in upper and lower extremities. Computerised tomography of the head revealed multiple enhancing lesions in both hemispheres. The patient’s visual, brainstem auditory, and somatosensory evoked potentials were abnormal and she had 12 white blood cells/nl CSF, cellulose with oligoclonal gammopathy on polyacetate electrophoresis and increased CSF IgG concentration (83 mg/dl, 24°of total proteins). The patient was treated with corticosteroiods with no indications of stabilisation in her neurological symptoms. Examination of peripheral blood and CSF revealed decreased OKT8/OKT4 cell ratio (033 and 026, respectively). After additional unsuccessful treatment with prednisone and subsequently with azathioprine and cyclophosphamide, the patient obtained TLI applied in individual doses of 200 rad per day to a total of 2000 rad over 57 days. During the observation period of 1375 days the patient had forty-seven neurological follow-ups and examinations for peripheral blood T cell subsets and B cells (table).2 On the modified disability scale used by Cook et all the patient regressed during the observation period from5 to 7. By the beginning of the second week after the start of the TLI, the patient showed a transient improvement in muscle strength in her legs and in her ability to walk, associated with a normal OKT8/OKT4 cell PERIPHERAL BLOOD T CELL SUBSETS IN
ratio. However, the ensuing eleven peripheral blood studies revealed decreased OKT8/OKT4 cell ratio with the lowest value (0-16) at the time when TLI ended after the total dose of 2000 rad. The OKT8/OKT4 cell ratio remained corrected since day 973 (182nd day from the first radiation treatment); however, muscle weakness progressed in the leg and right arm. Since the 12th day from the start of TLI, the patient’s lymphocyte count was below
1000/ul. In an individual MS patient failure of TLI to produce persistent normalisation in the peripheral blood OKT8/OKT4 cell ratio during the course of the radiation therapy may suggest subsequent suboptimal clinical results of the treatment. Departments of Neurology and Radiation Oncology, Indiana University Medical Center, Indianapolis, Indiana 46223, USA
O. J. KOLAR N. B. HORNBACK
1. Cook 2.
SD, Troiano R, Zito G, et al. Effect of total lymphoid irradiation in chronic progressive multiple sclerosis. Lancet 1986; i: 1405-09. Kolar OJ, Rice PH, Bauer DC, et al. Clinical implications of studies involving cerebrospinal fluid T-cell subpopulations. In: Multiple sclerosis present and future. New York: Plenum Press, 1983: 205-13.
PLACENTAL DRAINAGE AND FETOMATERNAL TRANSFUSION
SIR,-In your leading article (July 5, p 23) on the management of the third stage of labour, you wonder whether placental drainage would increase or reduce fetomatemal transfusion. We recently studied 141 consecutive primiparous women undergoing vaginal delivery, who were randomly allocated to one of two groups. Women in group 1 (72) had their placenta delivered in the conventional manner; the cord was clamped and the placenta delivered by controlled cord traction after signs of placental separation. In group 2 (69), the cord was clamped and cut after delivery of the infant; next the clamp was removed from the placental end of the cord and blood allowed to drain freely into a receiver. The placenta was then delivered by controlled cord traction and the volume of blood drained from the placenta was measured. Women in both groups received ’Syntometrine’ with delivery of the anterior shoulder. The mother’s haemoglobin level was measured two days after delivery and a Kleihauer test was
performed. In group 1 the volume of fetal red blood cells in the maternal circulation varied between 0 and 1-02 (mean 0-176) and in group 2 between 0 and 3-5 (mean 0- 114). The results were analysed with a t test for difference assuming unequal variances. Although the range of volume of fetal cells was much wider in the second group, there was no significant difference between the two groups in the amount of fetomaternal transfusion. Department of Obstetrics and Gynaecology, St George’s Hospital Medical School, Cranmer Terrace, London SW17 ORE
37-YEAR-OLD WOMAN WITH MULTIPLE
DEBORAH MONCRIEFF
JOHN PARKER-WILLIAMS GEOFFREY CHAMBERLAIN
SCLEROSIS WITH TOTAL LYMPHOID IRRADIATION