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The authors reply below: In response to Drs Ellerington, Whitehead and Stevenson's comments on our paper, we would like to raise the following points: (1) We do not agree with their comment that there is ample evidence that HRT is of value after 70 years of age. Indeed the paper by Quigley et aL1 (which they quote) shows no significant benefit from oestrogen in women over the age of 70 years. Other authors2'3 also refer to this paper and support our own view. Secondly, in neither of the other two references quoted4'5 is there any specific reference to the over-70s. Both studies have patients whose mean age is in the early 60s and neither can be legitimately extrapolated to comment on the behaviour of the over-70s. (2) We would agree that since planning our study in 1987, evidence is now available which shows that HRT decreases the risk of heart disease and would therefore no longer be a contraindication. (3) With regard to hypertension, our study involved a 4-month recruitment period. This time limitation precluded the inclusion of untreated hypertensives, but we did include treated hypertensives. (4) The trial was designed to look at the uptake of HRT as a forerunner of larger-scale work. Consequently it was seen as important to use one method of hormone administration as -HRT absorption has been shown to differ according to the route chosen6. (5) Premenstrual tension and bloating were only mild and were identified from the final questionnaire rather than as significant complaintsi They did not result in any withdrawals from the trial. (6) We are uncertain what constitutes a 'high' uptake of HRT which Drs Ellerington, Whitehead and Stevenson report in their letter. Even Christiansen et al.5 in Denmark in 1990, where there is greater awareness of HRT, only had an uptake of 44%. W A WALLACE Department of Orthopaedic and Accident Surgery, V H PRICE University Hospital, C A ELLIOT Queens Medical Centre, M B A MACPHERSON Nottingham NG7 2UH B W ScoTT References 1 Quigley MET, Martin PL, Bunier AM, Brooks P. Estrogen therapy arrests bone loss in elderly women. Am J Obstet Gynecol 1987;156:1516-23 2 Meuleman J. Osteoporosis and the elderly. Med Clin North Am 1989;73:1455-70 3 Resnick NM, Greenspan SL. 'Senile' osteoporosis reconsidered. JAMA 1989;261:1025-9 4 Lindsay R, Tohme JF. Estrogen treatment of patients with established osteoporosis. Obstet Gynecol 1990; 76:290-5 5 Christiansen C, Riis RJ. 17B estradiol and continuous norethisterone: a unique treatment for established osteoporosis in elderly women. J Clin Endocrinol Metab 1990;71:836-41 6 Savvas M, Studd JWW, Fogelman I, Dooley M, Montgomery J, Murby B. Skeletal effects oforal oestrogen compared with subcutaneous oestrogen and testosterone in post-menopausal women. BMJ 1988;297:331-3

Dental anaesthesia and dementia Trimmer in a letter about chronic snorers and sleep apnoea (December 1990 JRSM, p 813) suggests a relationship between dental anaesthesia and dementia. On what does he base this extraordinary

hypothesis? Surely an association as important as this should receive more prominence than a throwaway line on a different subject? The data, together with the statistical evidence and the control data should be published, at the earliest opportunity, in a peerreviewed journal, so that if necessary the dangerous practice of dental anaesthesia with its alleged attendant hypoxia, can be stopped forthwith. It is possible that we are over-reacting and Trimmer thinks that this is an amusing item. Unfortunately, this observation now becomes part of the established literature and may be quoted as an authoritative statement inside and outside the medical literature. The joke is in addition somewhat outdated. Anaesthetists, even in the practice of exodontia, are encouraged to monitor oxygenation nowadays'. It would be a pity ifthis ex cathedra statement were to be allowed to stand unchallenged. J N LUNN

J N HORTON

Department of Anaesthetics

University of Wales College of Medicine Cardiff CF4 4XN

References 1 Recommendations for standards of monitoring during anaesthesia and recovery. Association of Anaesthetists, 1988

Prospects for the treatment of multiple sclerosis The editorial by Hughes (February 1991 JRSM, p 63) rests upon a paradigm now nearly 60 years old. When intensive study of such a model yields virtually no results relevant to MS, it is time to re-examine it, especially since it was based originally upon analogy (Glanzmann; van Bogaert). If the EAE model be replaced by that of Gowers' (abiotrophy), now some 70 years old, which is supported by direct observation2, then the approach becomes heuristic in that it is 'open ended' and leads to further discovery and progress, and if successful, might indeed lead to the eradication of MS. Abiotrophy in action is strikingly illustrated by Figure 48 in Volume 9 of the Handbook3 - and this by a life long supporter (with occasional doubt) of the EAE model - the late Charles Lumsden. Allen et al4 are pushed to the conclusion that 'Categorization of MS material as plaque, peri-plaque and normal white matter may be arbitrary and may limit our thinking on the pathogenesis of the disease' a conclusion reached by the writer5 who has dealt with the situation fully. It is already possible to alter those capable of bearing MS offspring into individuals who do not so. Naturally the current numbers are small but astonishingly consistent. Of course with the now acknowledged existence of 'silent' cases of MS no individual can be exonerated from MS until autopsy. The writer would enter a strong plea for unbiased (if there be such) assessment of the closely examined pathology. To move a paradigm is no mean feat. History, however, has a way of casting doubt on the correctness of contemporary judgements; the Vatican, for instance, has recently decided to adjust its 'peer assessment' of Galileo! A properly organized programme aimed at elimination of MS based on the abiotrophy model can yield results within a generation, ie it is testable in

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this time. Thence it may be possible to eradicate the disease altogether (save for the 'silent' cases). E J FIELD Naomi Bramson Research Centre Science Park, University of Warwick

Coventry CV4 7EZ References 1 Gowers W. A lecture on abiotrophy. Lancet 1902;i:1003-7 2 Hassin GB. Studies in the pathogenesis of multiple sclerosis. Arch Neurol Psychiatry 1922;7:589-607 3 Lumsden CE. Neuropathology of multiple sclerosis. In: Vinken PJ, Bruyn GW, eds. Handbook of clinical neurology. Multiple sclerosis and other demyelinating diseases vol 9. Amsterdam: North Holland, 1970:66 4 Allen IV, McKeown SR. A histological, histochemical and biochemical study of the macroscopically normal white matter in multiple sclerosis. JNeurol Sci 1979;41:81-91 5 Field EJ. Conclusion: Can MS be virtually eradicated? In: Multiple sclerosis. A conceptual reappraisal with heuristic implications. Springfield, Illinois: CC Thomas, 1989:231-5

I was interested to read the article by Richard Hughes (February 1990 JRSM, p 63) on prospects for treatments in multiple sclerosis (MS), and note that in spite of reviewing some of the more exciting aspects of MS relevant research he remains 'gloomy' about specific immunotherapy. The fact there is an emerging consensus that MS is largely immunologically mediated can only be good news in the long term. Disappointments with steroids and aziothioprine are only to be expected because of their blunderbus effects re immunosuppression. It is important to remember that a huge global effort is underway to produce new generations of specific immunosuppressants. One such already available is FK506 and surely heralds the availability of many more prototype drugs for clinical testing. Whilst I agree with his multifactorial pathogenesis scenario I do not necessarily think that it should result in a gloomy outlook with regards to therapy. Indeed he referenced a final common pathway approach which is one of several requiring careful considered analysis. The discovery of T cell receptor (TCR) V(3 associations with multiple sclerosis which are not readily reproducible may indicate that VF3 TCR alone are not the causal association of MS, but instead suggest that MHC class II/V,8 combinations may be more likely to result in an immune response to a pathogen which results in neurological damage. After spending the last few years searching for the 'MS virus' it is refreshing to think that basic research has given us new tools to tackle how we may best design specific immunotherapies for this tragic disease, rather than search in vain for a specific causative agent to vaccinate against. This coupled with the aforementioned drug research programme should at least give us some hope to be optimistic about research into MS. A G DALGLEISH Clinical Research Centre Watford Road, Harrow HAl 3UJ

Marihuana and mouth cancer Boyle et al. in their review of the epidemiology of mouth cancer (November 1990 JRSM, p 724) .made no mention of marihuana smoking as a risk factor. During the last 5 years there have been 13 reports of cancer of the mouth and larynx among chronic marihuana smokers in Australia and the United

States'-3. Five of the 13 had no other risk factors and all were young (< 55 years old). The same literature search revealed only three reports of lung cancer amongst marihuana smokers2'4. This evidence suggests that marihuana smoking has a greater carcinogenic effect on the upper than the lower airways. If true this would correlate with respiratory function studies which demonstrate definite abnormalities in the proximal airways, but not in the peripheral airways5'6. It has been hypothesized that the rapid, deep inhalation technique usually employed in smoking marihuana leads to earlier deposition of particulate material due to turbulence and inertial impaction5. Whatever the reason, marihuana smoking as a possible cause of oral cancer deserves mention and further study. The Prince of Wales Hospital G A CAPLAN Randwick, NSW 2031, Australia References 1 Caplan GA, Brigham BA. Marijuana smoking and carcinoma of the tongue: is there an association? Cancer 1990;66:1005-6 2 Donald PJ. Marijuana smoking: possible cause of head and neck carcinoma in young patients. Otolaryngol Head Neck Surg 1986;94:517-21 3 Taylor FM. Marijuana as a potential respiratory tract carcinogen: a retrospective analysis of a community hospital population. South Med J 1988;81:1213-16 4 Ferguson RP, et aL Metastatic lung cancer in a young marijuana smoker. JAMA 1989;261:41-2 5 Taskin DP, et al. Respiratory status of seventy four habitual marijuana smokers. Chest 1980;78:699-706 6 Tashkin DP, et aL Respiratory symptoms and lung function in habitual heavy smokers of maruaa alone, smokers of marijuana and tobaoo, smokers of tobacco alone and nonsmokers. Am Rev Respir Dis 1987;136:209-16

Paget's disease of the anus I read with interest the case report by Rosin (February 1991 JRSM, p 112). I have now treated five elderly women with extramammary Paget's disease of the vulva with Etretinate. The first of these cases I reported in Retinoids (vol. 8, p 32). None of the patients was fit for extensive surgery and had an excellent response to a very small dose. I started all of them on 25 mg Etretinate daily and maintained them on 10 mg daily. There were few untoward sideeffects. On stopping treatment there was some mild recurrence but because of the mild nature ofthe sideeffects I have left them on Etretinate 10 mg daily almost indefinitely. Glan Clwyd Hospital E S EMSLIE Bodelwyddan, Rhyl, Clwyd LL18 5UJ

Pyoderma gangrenosum I was interested to read the letter by Heaton (February 1991 JRSM, p 123), regarding their experience of the use of cyclosporin A in a patient with pyoderma gangrenosum. We have also reported the successful use of this drug in a patient with a 14-year history of pyoderma gangrenosum unresponsive to a variety of systemic and topical treatments'. R K CURLEY

St Helens Hospital Marshalls Cross Road, St Heln WA9 3DA

References 1 Curley RK, Macfarlane AW, Vickers CFH. Pyoderma

gangrenosum treated with cyclosporum A. Br JDermatol 1985;113:601-4