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the Lewis lung carcinoma (3LL). This is an experimentaltumour syngeneic with C57Bl/6j mice which metastasisesspontaneously to the lungs when implanted intramuscularly. 10Intravenous injection of 3LL cells is followed by formation oflung colonies."

Treatment of mice with racemic sodium warfarin (RS) orwith its resolved enantiomers was started 2 days beforetumour-cell implant and continued until animals were killed.The prothrombin-complex activity was monitored every 2 daysby ’Thrombotest’10.12 and was consistently lower than 5% inanimals treated with either RS or S(-) warfarin. In contrast,it ranged between 90 and 110% in both R(+) warfarin treatedand control mice. 350 animals were used in this study.

Intravenous injection of 3LL cells induced an acute drop inblood platelets and other laboratory signs of acute dissemi-nated intravascular coagulation.1o The drop in platelet-countwas completely prevented in animals treated with racemic orS(-) warfarin; R(+) warfarin was ineffective. Similarly, devel-opment of lung colonies was significantly inhibited in micetreated with both warfarin preparations endowed with anti-coagulant activity; in contrast, mice treated with R(+) war-farin had lung colonies similar to control animals (table i).When 3LL-cells were implanted intramuscularly, both pri-

mary tumour and spontaneous lung metastases were signifi-cantly reduced in mice treated with RS or S(-) warfarin, butnot in mice treated with R(+) warfarin (table n).

These observations support Hilgard’s suggestion that anti-metastatic effect of oral anticoagulants is not related to a directaction of these compounds but requires impairment of vita-min-K availability. However, our results do not permit separa-tion of the anticlotting and antimetastatic effects of warfarin.In Hilgard’s experiments’3 diet-induced vitamin-K deficiencywas as effective as phenprocoumon, not only in inhibitingtumour growth and dissemination but also in inducing anti-coagulation. Whether anticoagulant and antimetastatic effectsafter reduced vitamin-K availability are independent conse-quences of a similar biochemical alteration of liver and cancercells, as suggested by Hilgard, remains to be demonstrated.We thank Dr A. Butti, Crinos, Villaguardia, Italy for supplying

warfarin and warfarin enantiomers. This work was supported bygrants NIH PHRB-1 R01 CA 12764-01 and CNR (Italian ResearchCouncil) 73.00400.04.

Laboratory for Hæmostasis andThrombosis Research,

Istituto di Ricerche Farmacolo

giche "Mario Negri",20157 Milan, Italy

ANDREINA POGGILUCIANA MUSSONILAURA KORNBLIHTTELISABETTA BALLABIOGIOVANNI DE GAETANOMARIA BENEDETTA DONATI

ADVERSE REACTIONS TO DRUGS

SIR,-Many letters in The La’1cet report on or refer to pos-sible adverse reactions to drugs. These letters represent impor-tant information, but are frequently case-reports in isolation.Reports concerning adverse reactions are communicated inother ways-e.g., to the manufacturers or the Committee on

Safety of Medicines. Would it not be more valuable to yourreaders if such letters were included in a separate section of the

journal and were subject to scrutiny by an expert in adversereactions who, with his experience and knowledge of otherreports, could add comments so as to put into perspective theclinical relevance of these letters?

Smith Kline & French Laboratories,Welwyn Garden City,Hertfordshire AL7 1EY W. L. BURLAND

***An editorial on this subject appears on p. 133.-ED. L.

10. Poggi, A., Polentarutti, N., Donati, M. B., de Gaetano, G., Garattini, S.Cancer Res. 1977, 37, 272.

11. Mayo, J. G., Laster, W. R. Jr., Andrews, C. M., Schabel, F. M. Jr. Cancerchemother. Rep. 1972, 56, 183.

12. Owren, P. A. Lancet, 1959, ii, 754.13. Hilgard, P. Br. J. Cancer, 1977, 35, 891.

Commentary from Westminster

From Our Parliamentary CorrespondentPrenatal Screening for Spina Bifida

THE Parliamentary campaign for the immediateestablishment of a national screening service for the pre-natal detection of spina bifida is destined to fail. The dis-pute, though, is not about whether such a service shouldbe introduced-but when. The Department of Healthand Social Security has in effect already accepted theidea in principle: it is resisting the prospect of any earlyintroduction. It will be several months before theDepartment has considered the views it received in re-sponse to its circular sent out six months ago suggestinga service on a regional basis. It is also awaiting theresults of a feasibility study being carried out in Cardiffon the incorporation into routine antenatal care of ablood test to detect high levels ofoc-fetoprotein.

Around 200 M.P.S from all parties have now signed aCommons motion tabled last week urging the immediatego-ahead for routine spina-bifida screening for all preg-nant women. The motion refers to the successful testingin 19 areas of the United Kingdom of a new screeningprocess "which by a simple and cheap antenatal bloodtest can indicate in the sixteenth week of pregnancy the

presence of a spina-bifida fetus". It refers to the Govern-ment’s admission that such a scheme if extended

nationally would cover its costs within a few years andexpresses deep concern about the apparent indefinitepostponement of routine national screening. Finally, iturges Mr David Ennals, Secretary of State for SocialServices, to establish immediately on a national scale thenecessary facilities to allow all pregnant women to beoffered "this safe and effective test as quickly as pos-sible". The man behind the campaign is Dr Keith

Hampson, Conservative M.p. for Ripon, who argues thatthis medical breakthrough could cut the rate of spina-bifida births by 90%. The test had been accepted as sound by the medical profession, but Ministers were un-willing to find the 1 million a year necessary to makethe screening nationally available. He says that over twoyears 18 000 women have been tested in 19 centres

throughout the country and he is particularly anxiousthat the service in these areas should continue. "The

breakthrough lies in being able to determine very earlyin the pregnancy (16 - 18 weeks) whether there is a highrisk of a deformed birth so that mothers-to-be can be

given further tests and the mother therefore be given theoption of an abortion if she so wishes. This does not posean ethical problem for the state; the choice of an abor-tion would lie with the individual mother. But at leastshe should know so that the heartbreak of having mal-formed children could be avoided". Dr Hampson (whois a PH.D., not a medical graduate) believes that theRoyal College of Obstetricians and Gynaecologists arebeing "over cautious" in doubting the safety of the test-ing procedures. "We know enough for the Governmentto immediately proceed with providing facilities on anationwide basis. The obstetricians are arguing thatthere is a risk of miscarriage from the amniocentesis andthat the test could wrongly indicate that a fetus wasmalformed. But there is no evidence for both of these".

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Despite the widespread support which Dr Hampson’smotion has received, the Government is proceeding withunderstandable caution on an issue which raises bothmedical and moral questions. The Department’s draftcircular last August suggesting a regional service hasbeen favourably received. But the Royal College ofObstetricians and Gynxcologists is urging a policy ofslow speed ahead. It is worried that the process ofamniocentesis could itself cause abortion and also aboutthe extent of false-positive results.

Last month Mr Roland Moyle, Minister of State forHealth, said he regarded the humanitarian argumentsfor a safe and effective screening service as paramount.Finance does not appear to be a problem. The blood*test would cost about 3 a head. Since the risk of thecondition varies greatly according to the geographicalregion, the cost of detecting a fetus with spina bifidamight range from z1000 to 4000. But in general it isaccepted that the cost of the demands which childrenwith spina bifida make on the N.H.S. exceeds the costof a programme to detect the condition. On the otherhand, the number of babies born alive with spina bifidais falling rapidly. The total for England and Wales was1180 in 1972 and, in the last year for which figures areavailable, 1976, it had dropped to 678.

The White-paper on Public ExpenditureThe protection which the National Health Service has

received from successive public expenditure cuts overthe past few years led to inevitable disappointment lastweek when the Government’s latest expenditure whitepaper revealed that there would be little growth inhealth and social services spending over the next fouryears. In comparison with other programmes, the healthprogramme appeared to be getting a raw deal. In factthe white-paper was simply a recognition that theN.H.S. has suffered less in recent years than other majorspending departments which, now that there is some-thing to spare in the public kitty, are demanding a rever-sal of the position.The result is that the increase in the health and per-

sonal social services programme over the next few yearswill actually be lower than the planned growth in publicexpenditure. The white-paper estimates that over theperiod to 1981-82 current expenditure on the hospitaland community health services will need to grow ataround 1% a year merely to cover the effects of demo-graphic change and make some small allowance for thecost of constantly improving medical techniques. Spend-ing on personal social services will need to grow at about2% a year, in particular because of the growing numbersof elderly people and of children in care. So the latestprogramme provides for this "minimum growth" withsome margin for development in 1981-82. Spending isforecast to increase by 2% from this year’s current levelof 7500 million and then at an annual rate of 1 -7% un-til 1981-82, when it will rise slightly.Compared with the last white-paper, expenditure has

been increased by ;E111 million in the current year. Butthis is largely as a result of additional construction workand the withdrawal of the road-traffic-accident chargesscheme, which would have brought in an extra C45 mil-lion a year from next year. The Government’s measuresto aid the construction industry will allow a steady levelof capital investment over the next few years which will

assist planning and allow "a modest programme" onnew developments.

But for health authorities perhaps the most gallingaspect of the white-paper is the admission that expendi-ture last year was just under 1% less in volume termsthan planned, mainly because the rate of inflation washigher than expected when cash limits were set. Sincethis was the first year of operating cash limits across70% of the health and personal social services pro-gramme, it could be said to be a fairly close match. Buthealth authorities which have cut services to the bone

may have little sympathy for the point.

Obituary

HECTOR MacLENNAN

Kt., M.D. Glasg., F.R.C.P., F.R.C.P.G., F.R.C.O.G.

Sir Hector MacLennan, president of the Royal Col-lege of Obstetricians and Gynaecologists in 1963-66, andconsultant surgeon to Glasgow Royal Maternity andWomen’s Hospital from 1934 to 1971, died on Jan. 6 atthe age of 72.

Having graduated M.B. from the University of Glasgow in1928 and M.D. in 1932, he practised in Glasgow for the restof his professional life-at the Victoria Infirmary as well as theMaternity Hospital. He was an external examiner in obstetricsand gynaecology to a number of British universities; he was amember of the Western Regional Hospital Board, Scotland, in1950-56, and of the General Medical Council in 1965-69. In1971 he became chairman of the advisory committee on dis-tinction awards. He served as president of the Royal Societyof Medicine and as chairman of the Medico-PharmaceuticalForum. His public service was not confined to medicine, for hewas also chairman of the Scottish Tourist Board in 1969-74and Lord High Commissioner to the General Assembly of theChurch of Scotland in 1975-76.

J. P. writes:"Hector MacLennan first became associated with the Royal

College of Obstetricians and Gynaecologists after passing hismembership examination, when he was awarded the Blair Belllectureship-the highest accolade that the College can give toa young member. His subject was contracted pelvis, of whichhe had made a special study in Glasgow. He was early electedto represent the members on the council, and for the nexttwenty years he served on most of the important College com-mittees, before being elected president in 1963. The Collegewas then firmly established in its new building in Regent’sPark, and he began to look further afield than the UnitedKingdom and the older dominions in order to spread the in-fluence of the College in improving the standards of obstetricsand gynaecology. He travelled widely in the Indian subcon-tinent and it was from the time of his presidency that stronglinks, both formal and informal, began to be forged with themany fellows and members who, having received much of theirpostgraduate training in the U.K., had returned to their owncountries. It was an expansionist policy which the College hascarried on ever since, and these links have been extended to in-clude many countries in Africa as well as India, Pakistan, andSingapore."MacLennan chaired the council and many of the College

committees with great skill and wisdom. He showed firm lead-ership, but at the same time he was always courteous and con-siderate, even with the most troublesome members, and he lis-tened to all views with a sympathetic ear. He presided over allthe College functions, both academic and social, with grace,