NAPROXEN SUPPOSITORIES IN PRIMARY DYSMENORRHŒA

278

produces anorexia contributing to weight loss as well perpetuating or potentiating the intestinal lesion, does not seem to be significant in most cases of subclinical malabsorp-

in sprue as

tion. The problem with surveys among populations in areas endemic for sprue is that it is impossible to know the status of the intestinal abnormalities in individuals examined on a single occasion. The early intestinal abnormalities in sprue are usually mild,IO making it difficult to distinguish whether intestinal changes detected during surveys represent an early phase of the progressive lesion of sprue or the relatively static abnormalities of subclinical malabsorption. It also remains difficult to be sure how to categorise intestinal abnormalities when they include steatorrhoea with malabsorption of xylose and/or vitamin B12, as in 5% or more of adults in rural populations surveyed in the West Indies.8 Repeated observations over a long period of time are needed to clarify the natural history of the intestinal lesion in such individuals. Although usually separate clinical entities, tropical sprue and subclinical malabsorption both appear to represent the response of the intestinal mucosa to contamination by enteric pathogens. Clinically, sprue often occurs as a sequela to acute diarrhoea and such has occurred in large groups of expatriates or native residents among whom sprue eventually developed in a small proportion of those afflicted by epidemic diarrhaea.11 12 Most persons have jejunal colonisation by coliform bacteria" which elaborate enterotoxins that produce, in short-term animal experiments, intestinal abnormalities resembling those present in persons with sprue. 14 15 It has been proposed that sprue represents an episode of acute diarrhoea due to colonisation by toxigenic coliform bacteria in which these enteric pathogens are not expelled from the gut after about a week, as occurs in the self-limited disorder known as turista, but persist with the result that prolonged exposure of the intestinal mucosa to the bacterial enterotoxins results in the abnormalities associated with sprue. 13-15 In accord with this hypothesis is the fact that irradication of the bacteria by antimicrobial therapy results in cure. 16 The basic defect in sprue then may be an inability to prevent persistent colonisation by toxigenic coliform bacteria. The factors responsible for this are unknown; dietary constituents, specifically linoleic acid, have been incriminated in some legions. 17 Subclinical malabsorption is also clearly a response of the intestinal mucosa to factors present primarily in tropical environments. Abnormalities of varying severity become evident during childhood among the indigenous population and after several months’ residence among expatriates; in both groups, the abnormalities are more prevalent among those residing in rural than in urban areas, and they eventually revert to normal after affected individuals have moved to a temperate climate. 18 There is little to suggest that these abnormalities are due to food toxins or parasitic infestations, but considerable evidence to incriminate enteric pathogens. They are usually detected in individuals who have experienced recurrent, selflimited attacks of infectious diarrhoea and such episodes have been found to be associated with transient structural changes, steatorrhcea, and monosaccharide malabsorption in some children, 11-2and malabsorption of xylose and/or vitamin B12 in some adults.22 It seems probable that multiple enteric pathogens are capable of producing such abnormalities. Of the two identified as the most common causative agents of acute 10.

O’Brien, W., England, N. W. J. Tropical Sprue and Megaloblastic Anæmia; p. 25. London, 1971. 11. Jones, T. C., Dean, A. G., Parker, G. W. Am. J. Epidemiol. 1972, 95, 111. 12. Baker, S. J., Mathan, V.I. Ann. trop. Med. Parasit. 1970, 64, 453. 13. Klipstein, F. A., Holdeman, L. V., Corcino, J. J., Moore, W. E. C. Ann. intern. Med. 1978, 79, 632. 14. Klipstein, F. A., Engert, R. F., Short, H. B. Lancet, 1978, ii, 342. 15. Klipstein, F. A., Horowitz, I. R., Engert, R. F., Schenk, E. A. J. clin. Invest. 1975, 56, 559. 16. Maldonado, N., Horta, E., Guerra, R., Perez-Santiago, E. Gastroenterology, 1969, 56, 559. 17. Klipstein, F. A., Corcino, J. J. Am. J. trop. Med. Hyg. 1974, 23, 1189. 18. Lindenbaum, J., Harmon, J. W., Gerson, C. D. Am. J. clin. Nutr. 1972, 25, 1056.

diarrhoea among persons in the tropics, rotavirus infection results in intestinal abnormalities in children (unpublished) and the enterotoxins of some coliform bacteria induce similar changes in laboratory animals. 15 These observations suggest that the intestinal abnormalities in subclinical malabsorption represent the residual effect of repeated episodes of transient colonisation by varied enteric pathogens and that those in sprue are the result of persistent contamination by one of them. Department of Medicine, University of Rochester Medical Center, Rochester, N. Y. 14642, U.S.A.

FREDERICK A. KLIPSTEIN

NAPROXEN SUPPOSITORIES IN PRIMARY DYSMENORRHŒA

SIR,-Primary dysmenorrhoea can be treated with oral prostaglandin-synthetase inhibitors.l2 One of them is naproxen sodium, which relieved dysmenorrhoea in 67-79% of the treatment cycles.3,4 Vomiting can be one reason for therapeutic failure of an oral treatment because dysmenorrhoea is associated with vomiting in 19-89% of cases.4-6 We have administered naproxen in rectal suppositories for the treatment of primary dysmenorrhoea. DYSMENORRHCEIC SYMPTOMS BEFORE AND DURING TREATMENT WITH PLACEBO OR NAPROXEN SUPPOSITORIES

Fifteen dysmenorrhreic women aged 17-26 years were given suppositories containing either 500 mg naproxen or placebo (Astra-Syntex, Sodertalje, Sweden) during two consecutive menstruations in randomised order. A patient inserted the first suppository at the onset of bleeding, and the dose was repeated every 4-6 h according to the patient’s own judgment; additional analgesics were allowed. Two women were excluded from the study before the code was broken; one woman did not follow the instructions and the other had an apparently anovulatory cycle with a period length of 6 weeks. Naproxen suppositories relieved dysmenorrhcea better than placebo (table). Twelve women preferred naproxen to placebo, and only one patient reported that both therapies caused a mild but similar relief. Twelve patients (92%) experienced excellent or good overall relief with naproxen whereas this happened in five women (38%) with placebo. On average 2.3 (1-5) naproxen and 2.7 (1-4) placebo suppositories were used. One patient complained of rectal irritation after naproxen use; no other side-effects were reported. 19. Barnes, G. L., Townley, R. R. W. Archs Dis. Childh. 1973, 48, 343. 20. MacLean, W. C., Klein, G. L., Lopez de Romana, G., Massa, E., Graham, G. G. J. Pediat. 1978, 92, 562. 21. Lifshitz, F., Coello-Ramirez, P., Gutierrez-Topete, G., Cornado-Cornet, M. C. J. Pediat. 1971, 79, 760. 22. Lindenbaum, J. Br. med. J. 1965, ii, 326. 1.

Schwartz, A., Zor, U., Lindner,

H. R., Naor, S. Obstet.

Gynec. 1974, 33,

709. 2. Ylikorkala, O., Dawood, M. Y. Am. J. Obstet. Gynec. 1978, 130, 833. 3. Henzl, M. R., Buttram, V., Segre, E. J., Bessler, S. ibid. 1977, 127, 818. 4. Lundström, V. Acta obstet. gynœc. scand. 1978, 57, 421. 5. Anderson, A. B. M., Haynes, P. J., Fraser, I. S., Turnbull, A. C. Lancet, 1978, i, 345. 6. Kauppila, A., Ylikorkala, O. Eur. J. Obstet. Gynœc. reprod. Biol. 1977, 7, 59.

279

Suppositories containing prostaglandin-synthetase

inhibi-

may prove better than tablets for the treatment of primary dysmenorrhoea. Local absorption may be more rapid and result in higher blood levels of anti-prostaglandins in the pelvic organs compared with oral administration. We are now comparing oral and rectal naproxen. OLAVI YLIKORKALA Department of Obstetrics and Gynæcology, ANTTI KAUPPILA University of Oulu, SF-90220 Oulu 22, Finland JUKKA PUOLAKKA tors

adult homozygote with only fetal haemoglobin within his vessels was the "C.A." of table n in an earlier paper9 where we showed clearly that there was imbalance of globin-chain synthesis. Ghana Institute of Clinical Genetics, Korle Bu Teaching Hospital, P.O. Box 150, Korle Bu, Ghana

F. I. D. KONOTEY-AHULU

"SEE IT DOESN’T HURT ..." ENTERITIS NECROTICANS IN NEPAL

SiR,-During a recent W.H.O. consultancy in Nepal on another matter, I was able to make some observations and inquiries about the possibility of enteritis necroticans being endemic there. The topography, terrain, and environment are very similar to those of the highlands of Papua New Guinea where the disease known as "pig-bel" is endemic. 1-3 The condition is caused by infection with Clostridium type C, present in the normal environment. This organism flourishes under changed ecological conditions.4-6 Its beta toxin, rapidly detoxified in the normal gut, penetrates the mucosa causing necrosis. The pathogenic outcome depends on the balance between the production and destruction of beta toxin. The disease is now preventable by vaccination (see p. 227). In the village setting in Nepal, the same ecological determinants exist as in Papua New Guinea. Protein deprivation in children (7%), ascaris infestation, faecal pollution of the environment, domestic pigs reared and cared for by lower caste Hindus, and seasonal gastroenteritis outbreaks following religious festivals with dietary change to meat and occasional consumption of sweet potato. Auxiliary health workers at several health posts, when questioned about the clinical features of acute pig-bel disease, agreed that they see cases. Surgeons at the Bir Hospital in Kathmandu recognise jejunal volvulus, usually associated with ascaris infestation, as the commonest cause of small-bowel obstruction met at laparotomy and recognise that cases appear to occur seasonally. It will be interesting to determine whether C. perfringens typeC is as widespread in the Nepali environment as it is in Papua New Guinea. Now that control by vaccination is feasible a search for undiagnosed cases of enteritis necroticans in other Asian, South East Asian, and Western Pacific countries where environments are similar might be useful. Department of Community Medicine, University of Adelaide, Adelaide, South Australia 5001

T. G. C. MURRELL

HOMOZYGOSITY FOR HEREDITARY PERSISTENCE OF FETAL HAEMOGLOBIN

SIR,-My attention has been drawn by Prof. Hermann Leh(Cambridge) and Prof. David Weatherall (Oxford) to an

mann

interpretation’ of the non-alpha/alpha chain ratio in the case of a blood-donor footballer who was homozygous for hereditary persistence of fetal hoemoglobin. The statement that there was no imbalance of globin-chain synthesis was incorrect, and we regret giving the opposite meaning while comparing our ratio with that of Charache et a1.8 who pointed out that "the Negro variety of hereditary persistence of fetal hxmoglobin" was a mild form of thalassaemia. Our error in our

(0.51)

1 Murrell, T. G. C., Roth, L. Med. J. Aust. 1963, i, 61. 2 Murrell, T. G. C., and others. Lancet, 1966, i, 127. 3 Murrell, T. G. C., and others. J. Hyg. Camb. 1966, 64, 375. 4. Egerton, J. R, Walker, P. D. J. Path. Bact. 1964, 88, 275. 5. Lawrence, G., Walker, P. D. Lancet, 1976,i, 125. 6 Walker, P. D., Murrell, T. G. C. J. Path. Bact. (in the press). 7 Acquaye, C. T. A., Oldham, J. H., Konotey-Ahulu, F. I. D. Lancet,

1977,

i, 796. 8

Charache, S , Clegg, J. B., Weatherall, D. Br.J. Hœmat. 1976, 34, 527.

Our peripatetic correspondent (Dec. 23/30, p. 1369) writes: "Dr May (Jan. 13, p. 103) has not read between the lines of my piece in In England Now. Neither Willie nor we would have dreamed of dissembling. Children are not fools; they easily saw through the ploy, but it still worked. Indeed, that was the beauty of it. Is not permissible pride a human emotion, too? And one that is not only to be encouraged, but productive of courage?"

9.

T. A., Oldham, J. H., Konotey-Ahulu, F. I. D. Yawson, G., Sukumaran, P. K., Schroeder, W. A., Huisman, T. H. J. Biochem. Genet. 1977, 15, 1083.

Ringelhann, B., Acquaye, C.

Commentary from Westminster From

Parliamentary Correspondent Conflicting Views on Cannabis our

PROPOSALS to liberalise the law on cannabis are being considered by the Home Secretary, Mr Merlyn Rees. They have been recommended to him by the Government’s Advisory Council on the Misuse of Drugs, which has just completed a review of the classification of controlled drugs and the penalties laid down. Its report, which has yet to be published, recommends that cannabis and cannabis resin should be downgraded to a lower category of drugs and that the penalties for unlawful possession should be relaxed. However, as Sir Robert Bradlaw, chairman of the Council, says in a letter to Mr Rees, the issue provoked "a marked division of opinion within the Council". Members were unanimous that the use of cannabis and cannabis resin should not be legalised and that a deterrent to their use was still needed. They rejected the idea of "decriminalisation" as adopted by several states in the U.S. There was also general agreement that any question of liberalising the present law should be approached with caution. Members were anxious that, whatever their recommendations, they should not lead to an increased use of the drug or to an increase in trafficking. The conflict of view arose over the harmfulness or otherwise of cannabis. The Council’s technical subcommittee, chaired by Prof. J. D. P. Graham, professor of pharmacology in the University of Wales, believed that lower penalties for unlawful possession could be contemplated without undue concern that this would encourage increased use and possible risk to public health. Its conclusion was "that there was no compelling evidence that occasional moderate use of cannabis was likely to have detrimental physical effects on individual users. The acute effect was one of intoxication and was dose related, temporary and reversible". After referring to evidence from America that the use of herbal cannabis (marihuana) impairs driving ability and that heavy use