335
practolol was the cause. Indeed, our Centre is very disturbed about this severe side-effect, which may have widespread tragic consequences. However, as the disorder was apparently observed long
before
practolol was introduced, the possibility must be recognised that other conditions and perhaps other drugs may be involved in producing " idiopathic fibroplastic peritonitis. "
than that encountered by Coltart and Coe, who report that 13 out of their 19 patients vomited. Department of Obstetrics and Gynæcology, New Medical School, University of Liverpool, Liverpool L69 3BX.
J. M. BEAZLEY J. F. B. CLARKE.
Netherlands Centre for Monitoring of Adverse Drug Reaction, 10 Dokter Reijersstraat,
Leidschendam,
R. H. B. MEYBOOM.
Netherlands.
DOCTORS AND SMOKING SIR,-In spite of a deep respect for the concerns Dr
ex-
I must emphasise that from a socio-economic and foremost from a personal philosophical point of view, premature death due to lung cancer or the cardiovascular consequences of smoking is a less frightening prospect than a living death with harassing cough and dyspnoea due to chronic bronchitis and emphysema. Many such patients would welcome death, but they usually survive to suffer years of misery, disability, and dependency. We should be motivated by a compelling desire to prevent this problem and not worry so disproportionately about those we lose along the way. After all, life without living is no life at all.
pressed by
Gray (Jan. 4,
University of Texas, Health Science Center at Dallas, P.O. Box 5999, Dallas, Texas 75222, U.S.A.
p.
41)
WILLIAM F. MILLER.
INTRAVENOUS PROSTAGLANDINS AND
OXYTOCIN FOR MID-TRIMESTER ABORTION
SIR,-We read with interest the letter by Mr Coltart (Jan. 18, p. 173) on the combined use of intravenous prostaglandin E2 and oxytocin (’ Syntocinon ’) in the management of mid-trimester therapeutic abortion. In a series of 19 cases, they report 100% successful
and Dr Coe
termination of pregnancy. The dose range of prostaglandin E2 employed, however, 2-5-10 g. per minute, in our opinion, remains unnecessarily high. This dose range is of the same order as that employed previously to terminate niid-trimester - pregnancy, I-a and has now been largely abandoned in view of the unacceptable incidence of sideeffects. The possible clinical application of oxytocin/prostaglandin E2 potentiation, permitting lower doses of intravenous prostaglandin E2 to be employed, with a consequent reduction in side-effects, was first pointed out by Beazley 4 in 1971. A preliminary trialestablished that the most likely effective combination of the two drugs would be: prostaglandin E2 2-0 .g. per minute; oxytocin 128 jg. per minute. Since then we have undertaken a clinical trial using this lower dose of prostaglandin E2 in combination with oxytocin in 85 patients at different periods of gestation up to 24 weeks. We have found that by this method effective stimulation of the uterus can be achieved from 14 weeks’ gestation. Moreover, apart from transient superficial phlebitis, the incidence of side-effects is considerably less Karim, S. M. M., Filshie, C. M. Br. med. J. 1970, iii, 198. Embrey, M. P. ibid. 1970, ii, 258. 3. Hillier, K., Embrey, M. P. J. Obstet. Gynœc. Br. Commonw. 1972, 79, 14. 4. Beazley, J. M. Prostaglandins in Fertility Control. Proceedings of W.H.O. Research and Training Centre on Human Reproduction; report IX, p. 102. Karolinska Institute, Stockholm, 1971. 5. Gillespie, A., Beazley, J. M., Ballard, R. M. Int. Res. Commun. System, August, 1973, (73-8) (10-26-1).
1. 2.
SPONTANEOUS CYTOTOXIC ACTIVITY AS A TEST OF HUMAN LYMPHOCYTE FUNCTION SIR,—Petranyi et al.l commented on the correlation which has been observed 2-4 between multiple sclerosis and HL-A 3, 7. They compared this finding with a similar correlation which they found between this HL-A haplotype and a low spontaneous cytotoxic activity of normal human lymphocytes against DBA/2 mouse embryonic fibroblast monolayer cells. The mechanism of this cytotoxicity, and its relevance as a functional test of human lymphocyte immunocompetence are unknown. We have established 6 a similar test of human lymphocyte cytotoxic ability which may measure the same properties as those described by Petranyi et al. The test is based on the observation thatFicoll ’/’ Isopaque ’-purified,7 7 monocyte-depleted,8,9 human lymphocyte preparations will lyse target cells from several mouse-tumour-cell lines, and is performed in microplates using chromium-51-labelled P815 mastocytoma cells in a chromium-release assay. It is simple, sensitive, reproducible, inexpensive, and can be performed at lymphocyte/target cell ratios of only 25/1 to obtain lymphocytemediated chromium release of up to 45% after overnight incubation, depending on the donor. Using ficoll-isopaque buoyant density centrifugation of rosette-forming cells (R.F.C.),lO two thymus-derived (T) cell preparations were made-(i) by the sedimentation of sheep erythrocyte rosette-forming cells (E-R.F.C.) followed by ammoniumchloride lysis of the red blood-cells (R.B.C.) (enriched for T cells with receptors for sheep[s] R.B.C.) 11 and (ii) by the sedimentation and removal of E.A.C.-R.F.C. (depleted by lymphocytes with receptors for complement activated by rabbit 19S anti-s.R.B.C. bound to S.R.B.C.).12 Each of these preparations consisted of 90-98% T cells, but neither showed significant spontaneous cytotoxicity (0-5%) at effector/target cell ratios of 20/1, and only slight cytotoxicity (5-13%) at ratios of 50/1. Depletion of T cells by E-R.F.C. sedimentation and removal slightly inhibited cytotoxicity, presumably as a result of having performed three rosette-formation and sedimentation cycles on these cells, which was necessary to give a population with less than 1 % T cells. These results were also obtained with spontaneous lymphocytemediated cytotoxicity (S.L.M.C.) against human cell-lines
(homologous s.L.M.c. as opposed to xenogeneic S.L.M.c.). 13 In conclusion, our data indicate that S.L.M.c. by human lymphocytes is not caused by thymus-derived cells, but, rather, is an index of the cytotoxic function of non-T lymphocytes, probably complement-receptor bearing lymphocytes. We hope that this test will prove to be a useful addition to the list of immunological properties which can Petrányi, G., Benczur, M., Ódony, C. E., Hollan, S. R., Iványi, P. Lancet, 1974, i, 736. 2. Jersild, C., Svejgaard, A., Fog, T. ibid. 1972, i, 1240. 3. Bertrams, J., Kuwert, E., Liedtke, N. Tissue Antigens 1972, 2, 405. 4. Naito, S., Namerow, N., Mickey, M. R., Terasaki, P. I. ibid. p. 1. 5. Petrányi, G., Iványi, P., Hollan, S. R. Vox sang. 1974, 26, 470. 6. Pross, H., Jondal, M. Int. J. Cancer (in the press). 7. Boyum, A. Scand. J. clin. Lab. Invest. 1968, 21, suppl. 97, 77. 8. Lundgren, G., Zukosi, C. F., Moller, G. Clin. exp. Immun. 1968, 3, 1.
817. 9. 10. 11. 12. 13.
Jondal, M., Klein, G. J. exp. Med. 1973, 138, 1365. Jondal, M. Scand. J. Immun. (in the press). Jondal, M., Holm, G., Wigzell, H. J. exp. Med. 1972, 136, 207. Bianco, C., Patrick, R., Nussenzweig, V. ibid. 1970, 132, 702. Jondal, M., Pross, H. Unpublished.