1314 have served as volunteers in pharmacological studies, some researchers whom I have interviewed contend that some drug companies that permitted employee-investigators to volunteer for drug studies in the past now have regulations prohibiting such practices, presumably for liability problems. We should know the extent of such regulations. New York Times, New York, N.Y. 10036, U.S.A.

Zambon S.p.A., Bresso, Milan, Italy 20091,

SIR,-I have received a disquieting number of complaints from members of the National Health Service Consultants’ Association that they had not received ballot papers for the vote on the consultant contract proposals. At a meeting of our executive committee, on June 6, of twenty consultants of whom we had knowledge (the consultant staff at Banstead Hospital, Sutton, at St John’s Hospital, Lincoln and in the department of microbiology at the Royal Free Hospital, plus those committee members not at any of these places) ten had not received ballot papers. Since then I have received further complaints from other members including some who have been in post for over ten years. I am not clear what the common denominator is amongst this large proportion of non-recipients but it does seem possible that members of the British Medical Association will be more likely to receive ballot papers than non-members. Ballott papers will be sent on request, but if this small sample is any way representative then a very large proportion of consultants will be put in this position and if there is bias, as suggested above, this must enhance C.C.H.M.S.’s likelihood of achieving a vote favourable to them from a quite non-representative sample of potential voters. Hon.





51 Gerard Road, London SW13 9QH

Since intermittent treatment for shorter periods may be safer and cheaper, without loss of efficacy, its trial on a larger scale seems justified.

it is, Dr Al-Dabbagh’s succinct of the contribution of Ibn al-Nafis to the discovery of the pulmonary circulation (May 27, p. 1148), calls for a com-

SiR,-Interesting though


plementary comment. The age of Ibn al-Nafis (the 13th century) was an age of medical renaissance in both Egypt and Syria, thanks to the work of the Iraqi physician Ibn al-Tilmidh (died 1165).1 It is barely credible that Ibn al-Quff (1233-86), a contemporary of Ibn al-Nafis, explained, ostensibly by pure logic based on close anatomical observation, the function of the capillaries which connect the arteries and veins, a discovery that Harvey himself was unable to make because the microscope was not available in his time. In 1661, however, the lot fell upon Marcello Malpighi2 who, four years after Harvey’s death, revealed with the aid of the microscope, results described by Ibn al-Quff four centuries earlier in his manual on the surgical art. He had also explained the working of the valves in the veins and the heart chambers, describing how they open in only one direction to keep blood flowing in the same way.3 Clarendon

Building, Bodleian Library,



SAM BAXTER Secretary, N.H.S.C.A.


SIR,-Your editorial of May 6 underlined the advantages of CHENODEOXYCHOLIC ACID

SIR,-In your helpful editorial on chenodeoxycholic acid (C.D.C.A.) (April 15, p. 805) you cite Iser et al.’ as supporting the view that "Intermittent therapy is ineffective". This is inal. did not try intermittent treatment in the examined the biliary effects of continuous C.D.C.A. treatment during the onset-offset phases. They did conclude that "intermittent treatment" is unlikely to be as effective as continuous treatment in dissolving gallstones", but by "intermittent" they meant, for example, treatment on alternate months. Studies in which I have been involved showed that even when the enterohepatic circulation of bile acids is largely interrupted (post-cholecystectomy, T-tube drainage), the increment in biliary C.D.C.A. (as % of total bile acids) produced by a 4-day treatment with 1.5 g/day C.D.C.A. (from 32.2% to 48.1%, means for 5 subjects for 4 days) was substantially maintained over the following 4-day period off C.D.C.A. so that the next 4-day treatment produced a further increment (from 47.5% to 58-8%)2. With a "4-day on/4-day off" regimen for c.D.c.A. (0 75-1.0 g/day) or a "4-day on/3-day off ’ regimen to fit the weekly cycle, the speed of litholysis (6 patients with stones disappeared or reduced at 3 months out of 14 examined) was no less than with continuous treatment (no patients out of 7 at 3-4 months).3 The proportions for treatments of up to 18 months were 9/21 and 5/13, respectively. After stone dissolution, C.D.C.A. 0-5 g/day was given on alternate weeks as maintenance and no recurrence occurred on this regimen, though some did after complete interruption.3·a accurate.






1. Iser, J. H., Murphy, G. M., Dowling, R. H. Gut, 1977, 18, 7. 2. Pliteri, S. Personal communication, 1973. 3. Garagnam A., Evangelisti, G. B., Casamichiella U., Faggioli, M. Clin. Ter. (in the press). 4. Mereto, G. C. Minerva gastroent. 1976, 22, 128.

D (’One-Alpha’, la-OHD) in urxmic pasynthetic drug avoids the need for renal hydroxylation, and if renal osteodystrophy is indeed due to a lack of renal la-hydroxylation of vitamin D the wide clinical use of la-OHD should be advantageous. However, certain clinical observations should dilute such optimism, suggesting that the essential point in the pathogenesis and therapy of the complex bone disease of urxmic patients is the hepatic 25-hydroxylation rather than the renal 1 a-hydroxylation of vitamin D.


tients. This


(a) Most patients with osteitis logical, biochemical, hormonal,

fibrosa or osteomalacia show radioand histological improvement after

vitamin D’even when anephric.s (b) The few patients who do not respond to high doses of vitamin D do not respond to la-OHD or to dihydrotachysterol (D.H.T.), while proving sensitive to 25-OHD.6 (c) There is a direct inverse correlation between plasma-25-OHD and the histological degree of osteomalacia in urasmia as well as in other metabolic disease.,8 (d) In the nephrotic syndrome there is a significant incidence of osteomalacia, due to the high renal clearance of plasma-25-OHD.99 (e) In anephric patients on maintenance hxmodialysis, who usually have high plasma levels of 25-OHD, quantitative bone biopsies show no evidence of osteomalacia.IOThis observation would also suggest that

Meyerhof, M., Schacht, J. (editors). The Theologus Autodidactus of Ibn alNafis; p. 8. Oxford, 1968. 2. Ullmann, M. Islamic Medicine; p. 690. Edinburgh, 1978. 3. Hayes, J. R. (editor) The Genius of Arab Civilisation: Source of Renaissance; p. 154. Oxford, 1978. 4. Verberkmoes, R., Bouillon, R., Krempien, B. Proc. E.D.T.A. 1073, 217. 5. Brancaccio, D., Graziani, G., Faccini, J. M., Banfi, G., Pedoja, G., Watson, L. J. urol. Nephrol. 1976, 82, 359. 6. Brancaccio, D., Graziani, G., Galmozzi, C., Ponticelli, C. Lancet, 1977, i, 1.


Eastwood, J. B., de Wardener, H. E. ibid. 1975, i, 981. Wake, C. J., Maddocks, J. L. ibid. 1975, i, 516. Barragry, J. M., France, M. W., Carter, N. D., Auton, J. A., Beer, M., Boucher, B. J., Cohen, R. D. ibid, 1977, ii, 629. 10. Bordier, P. J., Tun Chot, S., Eastwood, J. B., Fornier, A., de Wardener, H. E. Clin. Sci. 1973, 44, 33. 7. 8. 9.

Chenodeoxycholic acid.

1314 have served as volunteers in pharmacological studies, some researchers whom I have interviewed contend that some drug companies that permitted em...
155KB Sizes 0 Downloads 0 Views