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have served as volunteers in pharmacological studies, someresearchers whom I have interviewed contend that some drugcompanies that permitted employee-investigators to volunteerfor drug studies in the past now have regulations prohibitingsuch practices, presumably for liability problems. We shouldknow the extent of such regulations.New York Times,New York, N.Y. 10036, U.S.A. LAWRENCE K. ALTMAN

DISTRIBUTION OF BALLOT PAPERS

SIR,-I have received a disquieting number of complaintsfrom members of the National Health Service Consultants’ As-sociation that they had not received ballot papers for the voteon the consultant contract proposals. At a meeting of ourexecutive committee, on June 6, of twenty consultants ofwhom we had knowledge (the consultant staff at BansteadHospital, Sutton, at St John’s Hospital, Lincoln and in thedepartment of microbiology at the Royal Free Hospital, plusthose committee members not at any of these places) ten hadnot received ballot papers. Since then I have received further

complaints from other members including some who have beenin post for over ten years.

I am not clear what the common denominator is amongstthis large proportion of non-recipients but it does seem possiblethat 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 sam-

ple is any way representative then a very large proportion ofconsultants will be put in this position and if there is bias, assuggested above, this must enhance C.C.H.M.S.’s likelihood ofachieving a vote favourable to them from a quite non-represen-tative sample of potential voters.

51 Gerard Road,London SW13 9QH

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

CHENODEOXYCHOLIC ACID

SIR,-In your helpful editorial on chenodeoxycholic acid(C.D.C.A.) (April 15, p. 805) you cite Iser et al.’ as supportingthe view that "Intermittent therapy is ineffective". This is in-accurate. Iser et al. did not try intermittent treatment in the

study cited. They examined the biliary effects of continuousC.D.C.A. treatment during the onset-offset phases. They didconclude that "intermittent treatment" is unlikely to be aseffective as continuous treatment in dissolving gallstones", butby "intermittent" they meant, for example, treatment on alter-nate months.

Studies in which I have been involved showed that evenwhen the enterohepatic circulation of bile acids is largely inter-rupted (post-cholecystectomy, T-tube drainage), the incrementin biliary C.D.C.A. (as % of total bile acids) produced by a 4-daytreatment with 1.5 g/day C.D.C.A. (from 32.2% to 48.1%,means for 5 subjects for 4 days) was substantially maintainedover the following 4-day period off C.D.C.A. so that the next4-day treatment produced a further increment (from 47.5% to58-8%)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 theweekly cycle, the speed of litholysis (6 patients with stones dis-appeared or reduced at 3 months out of 14 examined) wasno less than with continuous treatment (no patients out of 7at 3-4 months).3 The proportions for treatments of up to 18months were 9/21 and 5/13, respectively. After stone dissolu-tion, C.D.C.A. 0-5 g/day was given on alternate weeks as main-tenance and no recurrence occurred on this regimen, thoughsome did after complete interruption.3·a

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.

Since intermittent treatment for shorter periods may besafer and cheaper, without loss of efficacy, its trial on a largerscale seems justified.

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

ARAB MEDICINE AND CIRCULATION OF THEBLOOD

SiR,-Interesting though it is, Dr Al-Dabbagh’s succinctaccount of the contribution of Ibn al-Nafis to the discovery ofthe pulmonary circulation (May 27, p. 1148), calls for a com-plementary comment.The age of Ibn al-Nafis (the 13th century) was an age of

medical renaissance in both Egypt and Syria, thanks to thework of the Iraqi physician Ibn al-Tilmidh (died 1165).1 It isbarely credible that Ibn al-Quff (1233-86), a contemporary ofIbn al-Nafis, explained, ostensibly by pure logic based on closeanatomical observation, the function of the capillaries whichconnect the arteries and veins, a discovery that Harvey himselfwas unable to make because the microscope was not availablein his time. In 1661, however, the lot fell upon Marcello Mal-pighi2 who, four years after Harvey’s death, revealed with theaid of the microscope, results described by Ibn al-Quff fourcenturies earlier in his manual on the surgical art. He had alsoexplained the working of the valves in the veins and the heartchambers, describing how they open in only one direction tokeep blood flowing in the same way. 3

Clarendon Building,Bodleian Library,Oxford S. A. KHULUSI

1&agr;-HYDROXYVITAMIN D

SIR,-Your editorial of May 6 underlined the advantages ofla-hydroxyvitamin D (’One-Alpha’, la-OHD) in urxmic pa-tients. This new synthetic drug avoids the need for renal hyd-roxylation, and if renal osteodystrophy is indeed due to a lackof renal la-hydroxylation of vitamin D the wide clinical use ofla-OHD should be advantageous. However, certain clinicalobservations should dilute such optimism, suggesting that theessential point in the pathogenesis and therapy of the complexbone disease of urxmic patients is the hepatic 25-hydroxyla-tion rather than the renal 1 a-hydroxylation of vitamin D.

(a) Most patients with osteitis fibrosa or osteomalacia show radio-logical, biochemical, hormonal, and histological improvement aftervitamin D’even when anephric.s

(b) The few patients who do not respond to high doses of vitaminD do not respond to la-OHD or to dihydrotachysterol (D.H.T.), whileproving sensitive to 25-OHD. 6

(c) There is a direct inverse correlation between plasma-25-OHDand the histological degree of osteomalacia in urasmia as well as inother metabolic disease.,8

(d) In the nephrotic syndrome there is a significant incidence ofosteomalacia, due to the high renal clearance of plasma-25-OHD.9 9

(e) In anephric patients on maintenance hxmodialysis, who usuallyhave high plasma levels of 25-OHD, quantitative bone biopsies showno evidence of osteomalacia.IOThis observation would also suggest that

1. Meyerhof, M., Schacht, J. (editors). The Theologus Autodidactus of Ibn al-Nafis; 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 Renais-

sance; 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,

22.7. Eastwood, J. B., de Wardener, H. E. ibid. 1975, i, 981.8. Wake, C. J., Maddocks, J. L. ibid. 1975, i, 516.9. 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.