731

dusts rich in B. subtilis enzymes. The nosebags containingchaff, once seen on street horses, must have provided a respira-tory challenge par excellence to the lungs of these animals.We suggest that in certain natural environments proteolytic

enzymes of bacterial origin may be respired and be potentiallydamaging to the lungs by allergic reaction, by direct in-

flammation, or by depletion or alteration of the protective in-fluence of cxi-antitrypsin on the lung surface, leaving thealveoli further exposed to tissue damaging enzymes of eitherintrinsic or extrinsic origin. This could be important in any un-explained lung condition where the patient has had environ-mental contact.

Department of Medicine,University of Sydney,Sydney, N.S.W. 2006, Australia

WESLEY F. GREENANN J. WOOLCOCK

1&agr;-HYDROXYCHOLECALCIFEROL AND RENALFUNCTION

SIR,-Clinical use of the biologically active vitamin-D meta-bolite 1,25-dihydroxycholecalciferol (1,25 [OH]2D3) and its

analogue lot-hydroxycholecalciferol (la-OHDg) is still at an

early stage. The main indication for these drugs is renal osteo-dystrophy. As stated in your editoriaP on ’One-Alpha’ it is

very important that the serum calcium x phosphate productis frequently measured since hypcrcalcsemia might cause

further deterioration in the renal function.

Tougaard et a1.2 reported a slight and insignificant reduc-tion of renal function in ursemic patients treated with

1IX-OHD3 when compared with untreated controls, and Win-terborn et al. recently supported their conclusion by demon-

Changes in serum-creatinine and creatinine clearance duringhypercalcaemia induced by treatment with lot-OHD3.

strating increased serum-creatinine in 4 uraemic childrentreated with la-OHD3. They found that the decline in glomer-ular filtration-rate (G.F.R.) appeared to be restricted to patientswhose renal function was already impaired. Kanis et al. how-ever, rightly stressed the importance of separating the directadverse effect of la-OHD3 and 1,25 (OH)2D3 from the meta-bolic consequences of their administration-i.e., changes inthe calcium x phosphate product and in the secretion of para-thyroid hormone, which might alter the renal function. Theydid not register any demonstrable adverse effect on renal func-tion in their patients with renal bone disease.We have treated patients with severe osteopenia of ageing

with lot-OHD, 1 6 and have been very concerned about any in-1. Lancet, 1978, i, 973.2. Tougaard, L., Sorensen, E., Brochner-Mortensen, J., Christensen, M. S.,

Rødbro, P., Sorensen, A. W. S. ibid. 1976, i, 1044.3. Winterborn, M. H., Mace, P. J., Heath, D. A., White, R. H. R. ibid. 1978,

ii, 150.4. Kanis, J. A., Cundy, T., Naik, R. ibid. p. 316.5. Lund, B., Hjorth, L., Kjær, I., Reiman, I., Friis, T., Andersen, R. B., Sør-

ensen, O.H. ibid. 1975, ii, 1168.6. Sorensen, O. H., Andersen, R. B., Christensen, M. S., Friis, T., Hjorth, L.,

Jørgensen, F. S., Lund, B., Melsen, F., Modekilde, L. Clin. Endocr. 1977,7, 1695.

fluence of the drug on renal function, particularly because theG.F.R. is reduced in the elderly population.’ 59 patients weretreated with la-OHD3 for 3-11 months. At first the patientsreceived a daily oral dose.of 2 g plus a calcium supplement,but because episodes of hypercalcsemia were frequent the dosewas reduced, and we now never use more than 1 g ofla-OHD3 and no calcium supplement. Hypercalcaemic episodeswere accompanied by rapidly decreasing G.F.R. and increasingserum-creatinine, but renal function was restored when thehypercalcsemia was corrected (see figure). 43 patients main-tained a normal serum-calcium during the treatment (groupA), while 16 patients developed 1-4 episodes of transitoryhypercalca:mia (group B). Renal function did not deterioratein the patients, but the initial creatinine clearance was lowerin group B (52-9±13-2 ml/min) than in group A (64-9±16-2)indicating an increasing risk of hyperca1caemia with decreasingG.F.R.

We follow our patients very closely (1-3 weeks interval) andconsequently the hypercalcaemic episodes have been of shortduration. More prolonged hyperca1caemia might result in irre-versible renal damage, so we support the conclusion in yourleading article’ that at present there is no justification forwidespread treatment of osteoporosis with 1,25 (OH2) D3 or ,

la-OHD3. We must await further results on the long-termeffect on bone and kidney.Department of Medicine E,Frederiksberg Hospital,Copenhagen, Denmark BIRGER LUND

Department of Medicine F,Herlev Hospital O. HELMER SØRENSENDepartment of Orthopædic Surgery,Frederiksborg Community Hospital BJARNE LUND

DOCTORS, DRINK, AND DISEASE

SIR,-In Canada and, I believe, in most of the western

world, death from cirrhosis of the liver is increasing. The rateof increase is closely correlated with the consumption of alco-hol. Your editorial on the prevention of alcoholic liver disease(Aug. 12, p. 353) reinforces my concern about whether thereis a serious desire within the medical profession to prevent cir-rhosis, and indeed all the problems associated with alcoholism.Avoidance of alcohol as a solution is dismissed by you in onesentence; that this could be a serious line of attack is not dis-cussed.You are right to say that abstinence from alcohol within our

society is out of favour. Perhaps one of the reasons why alco-holism is so high among British doctors2 is that medicalschools are excellent training grounds for the drinking habit.As I recall, just about all social activities, including official uni-versity functions, revolved around alcohol, and the patterncontinues when the doctor goes into practice. The only placewhere people met and talked was at a bar. As alcohol consump-tion increased, so the conversation became less intellectual. Atinternational, national, or local medical meetings, the socialfunctions inevitably involve liberal supplies of alcohol. I havebeen to conferences on the liver, including one on alcohol andthe liver, where the alcohol flowed freely. The outsider mightfind it hard to believe that doctors understand the dangers ofalcohol or that they are really interested in preventing alcohol-related disease.

I might take an alcohol researcher more seriously if I foundhe was a social abstainer. I had a recent experience with agroup of eminent people involved in cancer research. Their

7. Kampmann, J., Nielsen, K. S., Kristensen, M., Hansen, J. M. Acta med.scand. 1974, 196, 517.

1. Schmidt, W. in New York, 1977.2. Murray, R. M. Lancet, 1976, ii, 729.