ANTILEUKÆMIC ACTIVITY OF ASPARAGINASE

980 The remaining erythrocytes are then reinfused from the original donor bag into the patient. The transferred cells and plasma are now diluted 1/5 by the addition of sterile mixture 199. Penicillin and streptomycin are each added to a concentration of 300 (1.g. per ml. of total volume, and the highly purified glycoprotein octamer of P.H.A.8is then added to a concentration of 10 (1.g. per ml. of total volume. The transfer bag containing the diluted leucocyte suspension is then tightly sealed, incubated without agitation at 37°C for 24 hours, and then centrifuged at 800 g for 5 minutes at 2°C. The supernate bearing the unabsorbed P.H.A. is carefully transferred to a separate plastic bag by pressure from a plasma extractor, and the remaining lymphocytes and erythrocytes are resuspended in 300 ml. of a wash solution consisting of a heparinised 3/1 mixture of Earle’s basic salt solution and phosphate-buffered isotonic saline solution which is added to the bag. The suspension is then centrifuged in the bag at 800 g for 5 minutes at 2°C, the supernate again carefully transferred to a separate plastic bag, and the washing procedure of the cells repeated twice more to further remove residual P.H.A. and disintegrated granulocytes and platelets, and to further reduce lymphocyte and erythrocyte aggregation. The resultant washed lymphocytes are then resuspended in the bag with a 300 ml. volume of the wash solution, and the suspension of activated autologous lymphocytes is slowly infused at a rate of 2 ml. per min. through a filtered recipient line into a peripheral vein of the patient. The yield of autologous peripheral-blood lymphocytes during in-vitro activation and washing before reinfusion into a 42 kg. man with Ewing’s sarcoma metastatic to the lungs was as follows:

The peripheral-blood lymphocyte-count was 2300 per c.mm. at the time of the 420 ml. donation of whole blood. The reinfusion of the activated lymphocytes is well tolerated, with no suggestion to date of pyrogenic reactions, febrile responses, transfusion reactions, haemolysis, leucopenia,

thrombocytopenia, thromboembolism, or anaphylactic reactions. Tumour responses

are now

being evaluated.

Supported in part by grants CA-10174 and AM-01006 from the U.S. Public Health Service, and by a research-scholar award from the Leukemia Society. Division of Oncology, Department of Medicine, Stanford University School of Medicine, Palo Alto, California 94304.

JOHN H. FRENSTER WILLIAM M. ROGOWAY.

ANTILEUKÆMIC ACTIVITY OF ASPARAGINASE SIR,-I was interested to read the letter by Dr. Old and his colleagues (Sept. 21, p. 684), describing the increased antileukaemic activity of Escherichia coli asparaginase in mice infected with the lactate-dehydrogenase (L.D.H.)-elevating virus. Similar conclusions have been published elsewhere. 10 It is worth stressing that such viral infection is relevant to systems assaying tumour inhibition only in the mouse. The L.D.H. virus is not known to infect other species." Furthermore, in larger species, including man, the rate of clearance of high avidity E. coli asparaginase from the blood is much slower than in the normal mouse. In the latter animal the half-life is 2-3 hours,10 in the normal dog 12-13 hours, and in patients with various neoplastic diseases 22-48 hours.l2 In larger species such persistence is sufficient in itself for the production of tumour inhibition. Department of Pathology, New York-University School of Medicine, New York, New York 10016. 8. 9. 10. 11. 12.

J. D. BROOME.

Rigas, D. A., Johnson, E. A. Ann. N.Y. Acad. Sci. 1964, 113, 800. Stanley, D. A., Frenster, J. H., Rigas, D. A. J. Cell Biol. (in the press). Broome, J. D. Br. J. Cancer, 1968, 22, 595. Notkins, A. L. Bact. Rev. 1965, 29, 143. Cooney, D. P., Handschumacher, R. E. Unpublished.

TREATMENT OF MIGRAINE WITH PROPRANOLOL SIR,-The interesting report of treatment of angina pectoris and coexistent migraine with propranololprompts us to describe a similar case. A doctor aged 55 had a 25-year history of periodic headache and nausea. He had attacks at monthly intervals, and was unable to work for 4 or 5 days with each attack. The serious headache and nausea were produced most often by weather conditions, generally by intrusion of warm air masses. Since November, 1967, he has been taking propranolol (’Inderal’) 10 mg. three times a day for extrasystoles. At this dosage he has remained free from extrasystoles, but he has also reported freedom from attacks of migraine. He has been symptom-free for 9 months. This is all the more remarkable, because of the predominantly tropical weather (90-99°F, 32-37°C) in Hungary for 1 month during this period. After 9 months he stopped taking propranolol, but 3 weeks later he reported headache and nausea again, although in a milder form than He was persuaded to resume propranolol therapy, and these symptoms were completely relieved. This man has had no anginal pain (which was the reason for prescribing propranolol in Wykes’ four cases). We suggest that beta-receptor-blocking agents may have promise in the treatment of migraine.

previously.

We thank Inderal’.’.

Imperial Chemical Industries Ltd. for

the

supply

of

M. BÉKÉS L. MATOS J. RAUSCH E. TÖRÖK.

Department of Clinical Pharmacology, Hungarian Institute of Cardiology, Budapest IX, Nagyvárad tér 1, Hungary.

SIMON YUDKIN MEMORIAL CENTRE SIR,-Dr. Simon Yudkin, consultant paediatrician to the Whittington Hospital and University College Hospital, died in April at the age of fifty-four. His many colleagues may like to know that a group of his friends, not only representing medicine but also reflecting his great interest in the wider social aspects of child care, have decided to launch an appeal for a memorial fund. We hope that it may prove possible to establish and maintain through the money thus collected a centre in one of the hospitals at which he worked. This centre, while providing nursery accommodation for the healthy children of hospital staff, would also permit paediatricians to place their young children with potential or established handicaps. Such children could be observed and assessed against the background of normal behaviour and their development would benefit greatly from such an association with normal children. We know that Dr. Yudkin had such a centre in mind and feel that it would provide a worthy memorial to him. Contributions to the Simon Yudkin Memorial Trust and requests for covenant forms should be sent to Prof. Sir Max Rosenheim, c/o Mr. S. Wainwright, 6 Heath Close, London N.W.11. WILFRID G. HARDING MAX ROSENHEIM.

CHRISTMAS GIFTS FUND SIR,-May I be allowed through your columns to make known to all members of our profession that the Royal Medical Benevolent Fund make a special Christmas gift to all their regular beneficiaries ? We would be grateful for help in raising the

sum

needed and

hope that there will be a generous response

to our appeal. Donations, marked " Christmas Gifts ", should be sent to the Royal Medical Benevolent Fund, 24 King’s Road,

London S.W.19. ZACHARY COPE President, Royal Medical Benevolent Fund. 1.

Wykes, P. Practitioner, 1968, 200, 702.