642

syndrome or a recrudescence of her pneumonia is unclear. What is clear, however, is that the use of ketorolac adequately controlled the pain, without constipation and hypoventilation. Ketorolac is a water-soluble parenteral non-steroidal antiinflammatory drug with analgesic, anti-inflammatory, and antipyretic activity. It does not cause respiratory depression, is not addictive, and has proved effective in postoperative and cancer pain.4Ketorolac’s analgesic effect is almost equivalent to that of morphine. Children’s Hospital, Boston, Massachusetts 02115, USA 1.

Gold therapy in rheumatoid arthritis SIR,-In your July 6 editorial you claim that only 20% of patients who embark on gold therapy continue to receive the drug after five years. This has not been our experience. We feel that discontinuation of therapy is either attributable to lack of adequate counselling or trivial side-effects. We have followed 78 patients who were started on intramuscular gold for ten years. About half continued with this treatment at the end of this period (figure). All

ELIZABETH GOODMAN

Sprinkle RHG, Cole T, Smith SJ, et al. Acute chest syndrome in pediatric patients with sickle cell disease: a retrospective analysis of 100 hospitalized patients. Am J

Pediatr Hematol Oncol 1986; 8: 105-10. 2. Palmer J, Broderick KA, Naiman JL. Acute lung syndrome during painful sickle cell crisis: relation to site of pain and narcotic requirement. Blood 1983; 62 (suppl 1): 59a. 3. Ponez M, Kane E, Gill FM. Acute chest syndrome in sickle cell disease: etiology and clinical correlates. J Pediatr 1985; 107: 861-66. 4. DiPalma JR. Ketorolac: an injectable NSAID. Am Fam Physician 1991; 43: 207-10. 5. Powell H, Smallman JM, Morgan M. Comparison of intramuscular ketorolac and morphine in pain control after laparotomy. Anaesthesia 1990; 45: 538-42. 6. Buckley MM, Brogden RN. Ketorolac: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential. Drugs 1990; 39: 86-109. 7. Power I, Noble DW, Douglas E, Spence AA. Comparison of i.m. ketorolac trometamol and morphine sulfate for pain relief after cholecystectomy. Br J Anaesth 1990; 65: 448-55. 8. Carlson RW, Borrison RA, Sher HB, et al. A multiinstitutional evaluation of the analgesic efficacy and safety of ketorolac tromethamine, acetominophen plus codeine, and placebo in cancer pain. Pharmacotherapy 1990; 10: 211-16.

Malaria, bednets, and mortality SIR,-Dr Alonso and colleagues (June 22, p 1499) report a significant reduction of all-cause mortality and malaria mortality in children aged 1-4 years of age in The Gambia. They state that "the overall reduction in mortality was greater than that which would have been expected from the prevention of deaths directly attributable to malaria" and conclude "that the importance of malaria as a direct and indirect cause of death has been underestimated". We offer an alternative explanation.

Chemoprophylactic drugs or placebo were given individually to each child by the village health worker (VHW) on a weekly basis in villages with impregnated bednets but not in control villages. This regular personal contact of the VHW with the children had a protective effect independent of malaria chemoprophylaxis. In a study from Benin,’ children seen by the VHW had a significantly lower risk of dying in the next six months than children not seen (relative risk 0 33). This protection was not limited to malaria deaths and could not be attributed to a specific action of the VHW, such as preventive and/or curative treatment of malaria. Our interpretation of this finding is that needed curative or preventive medical care was provided to children whose parents might not have sought it for them on their own initiative. Similarly in the Gambian study, children in primary health care (PHC) villages were more likely to receive appropriate medical attention because they were personally seen each week by the VHW. This explanation is not to discredit Alonso et al’s principal result of a reduction of childhood mortality through the introduction of impregnated bednets. Their data show clearly that malaria mortality is reduced equally in those receiving ’Maloprim’ or placebo as a consequence of the impregnation of bednets. Curative treatment of malaria by the VHW could not explain this reduction since chloroquine was detected less frequently in urine samples from PHC villages than from non-PHC villages. In addition, however, there has been a non-specific protective effect on overall mortality related to the regular individual contact between the VHW and the children. Institute for Health Care in Developing Countries,

Faculty of Medicine, University of Nijmegen, 6500 HB Nijmegen, Netherlands

JOHAN P. VELEMA

JP, Alihonou EM, Gandaho T, Hounye FH. Childhood mortality among users non-users of primary health care m a rural West African community. Int J Epidemiol 1991; 20: 474-79.

1. Velema

and

Time on gold treatment in 78 patients.

patients were under the care of one clinician and special effort was made to ensure that patients were only withdrawn if there was a clear persistent trend towards worsening clinical state, rather than on the basis of isolated laboratory abnormalities. We feel that intramuscular gold therapy in rheumatoid disease is effective and useful, and with careful supervision most patients started on this treatment can be expected to continue it in the long term. Department of Rheumatology, Leicester Royal Infirmary, Leicester LE1 5WW, UK

A. SAMANTA S. ROY K. L. WOODS

Ethnic distribution of

myotonic dystrophy gene

SIR,-Myotonic dystrophy (DM) is the most prevalent muscular dystrophy in Western Europe, North America, and Japan.’ Although it is thought to afflict all ethnic groups, its incidence in some major ethnic populations is not well documented. We sent questionnaires to major referral medical facilities serving ethnic populations, inquiring for estimates of total and regional ethnic DM patients referred within the past five years. As a control, we also asked about Duchenne muscular dystrophy (DMD), which has a homogeneous distribution in the prevalence range 19-48 per 100 0002 world wide. Regional DM populations that have interbred with immigrants were excluded from the defined regional ethnic groups. We sent questionnaires to 127 centres, and 25 (20%) in twenty countries responded. In specific ethnic populations of India, Israel, Cyprus, and Eastern Europe and in immigrants within Nigeria, South Africa, Tunisia, Australia, New Zealand, and Israel, the estimated prevalence was comparable with that for western Europe (over 2 per 100 000).1 In South Africa, three major facilities, which draw from a population of more than 30 million, reported no regional ethnic DM cases. Only one DM family (Yoruba)3 was found in Nigeria (population 120 million) for the past 31 years. No DM cases were seen in Tunisian Berbers. Among specific Ethiopian ethnic groups, 3 DM patients (Amhara and Tigre) were found while 19 DMD patients were identified.’ In southern China, 6 patients were found among a Cantonese population in which 67 DMD cases were reported. In 53 million ethnic Thai, no DM has been reported. In Australia, two Aborigines (mixed with Pacific Islander and Maori, respectively) had DM among the 700 000 non-Europeans. As judged by the number of DMD patients seen, referral bias is unlikely. In Latin America, the representation of

643

POPULATIONS

GENETIC RELATIONSHIP

Genetic tree of populations studied.

Populations in bold face have prevalence of DM higher than 2

per

100000, whereas other populations have lower prevalence as suggested by our study. Genetic studies suggest that Ethiopians in part the Causasoid group while Berbers join the African group 20% of the time.’

join

regional ethnic populations seen by the responders were too small to estimate the prevalence of DM. Our survey suggests a very low prevalence of DM among ethnic Africans, especially in central and southern Africa. Cantonese, Thai, and probably Oceanians had a low prevalence too. Published data accord with our results. There have been no reported native DM cases in the reviews of neuromuscular or genetic disorders in Africa, despite an incidence of DMD similar to that for western nations.S-7 In southern China, prospective examination of 152 000 people in Guangdong (Canton) province led to finding no DM while 6 DMD patients were identified.8 Our observation is consistent with evolution and migration of the human species from Africa. On the basis of linguistic and genetic data9 the human species can be divided in three major groups (figure). If the mutation responsible for DM occurred in the North Eurasian groups migrating out of Africa to Europe, Southwest Asia, Korea, and Japan, the pattern of the DM gene distribution suggested by our survey can be explained. Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USA

that a very low concentration of cyclosporin, or the absence of the drug in blood, is unlikely to be associated with a therapeutic effect. Sowden et al have failed to identify adequately not only the analytical method used for cyclosporin measurements but also whether these measurements were made in whole blood or plasma. Since the concentration of cyclosporin varies both with the analytical method used and with the matrix in which it is measured,1 the concentration data they supply cannot be interpreted. In addition, they report the concentrations only as a range, without any measure of central tendency or dispersion. However, irrespective of any analytical method for the measurement matrix, at least one patient on active treatment clearly had a cyclosporin concentration (12 ug/1) that is indistinguishable from zero;2,3 another had a concentration of 784 )ig/l, which is consistent with toxic effects.4-6 Was the cyclosporin dose of 5 mg/kg per day given as a single or as divided doses? The use of the former regimen in relatively healthy individuals could give rise to high peak concentrations of the drug without maintaining the cyclosporin blood concentration throughout 24 h. High peak concentrations have been associated with diminished renal functionAdministration of the drug in divided doses would sustain the cyclosporin blood concentrations at a higher level, while avoiding excessive peak values. In our view, the simple expedient of individualising each patient’s cyclosporin dose, by measurement of their cyclosporin blood concentration and adjustment of their dose to avoid the recurrence of either very low or very high concentrations, could have mitigated the rise in serum creatinine and urea, and decreased the frequency of adverse side-effects, without compromising cyclosporin efficacy.

to assume

STUDIED

TETSUO ASHIZAWA HENRY F. EPSTEIN

1. Harper PS. Myotonic dystrophy, 2nd ed. London: Saunders, 1989. 2. Walton J, Gardner-Medwin D. The muscular dystrophies. In: Walton J, ed. Disorders of voluntary muscle. Edinburgh: Churchill Livingstone, 1988: 519-68. 3. Dada TO. Dystrophia myotonica in Nigerian family. E Afr Med J 1973; 50: 213-28. 4. Heimanot RT. Myopathies in Ethiopia. Afr J Neurol Sci 1986; 5: 23-30. 5. Spillane JD. Tropical neurology. London: Oxford University Press, 1973. 6. Beighton P, Botha MC. Inherited disorders in the black population of southern Africa. II: gene disorders. S Afr Med J 1986; 69: 293-96. 7. Dada TO. Muscular dystrophy of Duchenne type in Nigerians. J Neurol Sci 1967; 4: 435-44. 8. Liu Z-L, Liang X-L. Genetics in neurology. Beijin: People’s Epidemiologic Press, 1988. 9. Cavalli-Sforza LL, Piazza A, Menozzi P, Mountain J. Reconstruction of human evolution: bringing together genetic, archaeological, and linguistic data. Proc Natl Acad Sci USA 1988; 85: 6002-06.

Treatment of severe refractory atopic dermatitis with cyclosporin SIR,-Dr Sowden and colleagues (July 20, p 137) present very encouraging data on the use of cyclosporin in the treatment of adults with refractory atopic dermatitis. However, their results might have been improved had they used a more rational approach to cyclosporin dose. The pharmcokinetics of cyclosporin vary greatly between individuals. Therefore the fixed-dose treatment regimen used in this study would probably have produced very diverse blood concentrations in these patients. Although no therapeutic or target range for cyclosporin blood concentrations have been established in the treatment of dermatological diseases, high blood concentrations of the drug are known to reduce renal function. It is also reasonable

The Analytical Unit, St Georges Hospital Medical School, London SW17 0RE, UK

ATHOLL JOHNSTON DAVID W. HOLT

DW, Marsden JT, Johnston A. Measurement of cyclosporine: methodological problems. Transplant Proc 1986; 18 (suppl 5): 101-10. Holt DW, Marsden JT, Johnston A. Quality assessment of cyclosponne measurements: comparison of current methods. Transplant Proc 1990; 22:

1. Holt

2.

1234-39.

Johnston A, Cullen G, Holt DW. Quality assurance for cyclosporin assays in body fluids. Ann Acad Med Singapore 1991; 20: 3-8. 4. Holt DW, Marsden JT, Johnston A, Bewick M, Taube DH. The relationship between cyclosporin blood concentrations and renal allograft dysfunction. Br Med J 1988;

3.

293: 1057-59. BD, Shaw LM, Holt DW, Grevel J, Johnston A. A consensus document: Hawk’s Cay meeting on therapeutic drug monitoring of cyclosporine. Clin Chem

5. Kahan

1990; 36: 1510-16. D, Marsden JT, Palmer A, Cairns T, Johnston A, Holt DW. Value of

6. Taube

7.

cyclosporine measurements in renal transplant recipients immunosuppressed with triple therapy. Transplant Proc 1990; 22: 1251-52. Fashola TOA, Johnston A, Counihan P, Pepper JR, Holt DW. Blood cyclosporin absorption profiles and renal function in heart transplant recipients. Br J Clin Pharmacol 1991; 31: 236-37P.

SIR,-Dr Sowden and colleagues demonstrate the benefits of cyclosporin in adults with severe refractory atopic dermatitis. They comment that "although renal function worsened during cyclosporin therapy, these changes were neither statistically significant nor clinically important". This statement was based on serum creatinine concentrations in 33 patients given cyclosporin at a dose of 5 mg/kg per day for 8 weeks. Cyclosporin is known to cause reversible impairment of both glomerular filtration rate (GFR) and renal perfusion in the short term but in long-term treatment (probably after 6 months’ treatment) impairment becomes 300..

Relation between plasma occasions in 20 patients.

creatinine and

GFR

on

100

Ethnic distribution of myotonic dystrophy gene.

642 syndrome or a recrudescence of her pneumonia is unclear. What is clear, however, is that the use of ketorolac adequately controlled the pain, wit...
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