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message of your editorial (Oct 6, p 846) and its plea for less bureaucracy in ethics, something with which Walshe and I are in full agreement. Mid Glamorgan Health Authority Princess of Wales Hospital,

Ogwr Health Unit,

Bridgend CF31 1RQ, UK

D. E. B. POWELL

SiR,—Iwas saddened by two aspects of Dr Walshe’s comments on ethics committees. Firstly, he seems to suggest that members of these committees are self-seeking individuals intent on holding back medical research rather than looking after the welfare of patients who are, after all, what health care is about. Secondly, Walshe would place only "some" constraint on "unjustified experiments on patients". Such attitudes strengthen the need for ethics committees in order to minirnise "unnecessary harassment" of patients rather than of the "honest and competent research workers" about whom Walshe is concerned. Department of Public Health Medicine, North Bedfordshire Health Authority, Bedford MK40 2NU, UK

P. A. KITCHENER

Plasma endothelin and renal function during infrarenal aortic crossclamping and nifedipine infusion SIR,-Infrarenal aortic crossclamping induces transient renal vasoconstriction with a subsequent fall in renal blood flow (RBF) and glomerular filtration rate (GFR)/ which is not prevented by the administration of mannitol and dopamine.2 The pathogenetic mechanism is unknown. High levels of endothelin, a vasoactive peptide that can increase peripheral resistance and decrease cardiac output, RBF, and GFR3 have been found in plasma of patients undergoing abdominal surgery.’ Furthermore, the endothelin vasoactive action is dependent on extracellular Ca concentration.5 We therefore question that infrarenal aortic crossclamping might enhance endothelin production and that Ca blocker administration might prevent the renal vasoactive action of endothelin. In 5 patients who underwent infrarenal aneurismectomy we measured plasma endothelin before the induction of anaesthesia, at the beginning of the clamping period, at the end of the clamping period, and at the end of operation. In all patients anaesthetic management included haemodynamic monitoring (Swan-Ganz catheter), intravenous anaesthesia (flunitrazepam, fentanyl, pancuronium), and ventilation with an 02/air mixture. After operation patients received intensive care for 24-36 h. No patient received diuretics or vasoconstrictor agents. In all patients nifedipine (0’006-0’04 mg/kg per h) was infused intravenously (iv) from the beginning of crossclamping until the end of operation. GFR was measured the day before and immediately after operation (5’CrEDTA). Creatinine clearance was also measured before, during, and after aortic crossclamping. Plasma endothelin was evaluated by radioimmunoassay (endothelin-1,2 assay system, Amersham) after chromatographic purification with ’Amprep 500’ (Amersham). No perioperative episodes of low cardiac output were noted. Mean plasma endothelin concentrations rose significantly during

clamping (figure) and fell thereafter. In all patients creatinine clearance remained stable before, during, and after clamping; postoperative GFR did not change. We have shown that infrarenal aortic crossclamping induces a transient but significant increase of endothelin plasma concentrations. However, the infusion of Ca blockers prevents any substantial peptide effect on GFR during and after operation.

Miyauchi et al6 showed that the in-vitro vasoconstrictor response to endothelin-1 was effectively antagonised by nicardipine. Furthermore, Bolger et al5 reported that the rapid phase of contraction of aortic tissue was abolished by preincubation with nifedipine. These data suggest an action of endothelin on Ca influx closely associated with voltage-dependent channels.

However,

Chabrier et al7 have shown that Ca blockers are not effective on endothelin-evoked vasoconstriction in isolated vessels and vascular smooth-muscle cells. Our data show that in-vivo nifedipine can prevent the vasoconstrictive action of endothelin on the renal vascular bed. Departments of Nephrology and I Department of Anaesthesia, Ospedale Regionale, Udine 33100, Italy; and Department of Nephrology, University of Padua

F. ANTONUCCI M. BERTOLISSI L. CALO

1. Gamulin Z, Forster A, Morel D, Simonet F, Aymom E, Favre H. Effects of infrarenal aortic cross clamping on renal hemodynamics in humans. Anesthesiology 1984; 61: 394-99. 2. Paul MD, Mazer CD, Byrick RJ, Rose DK, Goldstein MB. Influence of mannitol and dopamine on renal function during elective infrarenal aortic clamping in man. Am J Nephrol 1986; 6: 427-34. 3. Miller WL, Redfield MM, Burnett JC. Integrated cardiac, renal, and endocrine actions of endothelin. J Clin Invest 1989; 83: 317-20. 4. Hirata Y, Itoh K, Ando K, Endo M, Marumo F. Plasma endothelin levels during surgery. N Engl J Med 1989; 14: 1686. 5. Bolger TB, Liard F, Jaramillo J. Tissue selectivity and calcium dependence of contractile responses to endothelin. J Cardiovasc Pharmacol 1990; 15: 947-58. 6. Miyauchi T, Tomobe Y, Shiba R, et al. Involvement of endothelin in the regulation of human vascular tonus. Circulation 1990; 81: 1874-80. 7. Chabrier PE, Auguet M, Roubert P, et al. Vascular mechanism of action of endothelin, I: effect of Ca antagonists. J Cardiovasc Pharmacol 1989; 13 (suppl 5): S32-35.

Infant botulism due to Clostridium botulinum type C toxin SiR,-Since 1976 more than 800 cases of infant botulism have been reported, most in the USA. All cases have been caused by type A or B toxin, with the exception of 3 caused by types E and F .1,;! The fulminant type of infant botulism may be responsible for cases of sudden infant death syndrome (SIDS) by causing paroxysmal dyspnea. We report the first outbreak of infant botulism with Clostridium botulinum type C toxin. A 171-day-old female was admitted to our emergency room for sudden onset of shallow respiration in February, 1990. She had had normal development, being fed on formula milk until about 2 months old, when commercial baby food, noodles, and vegetable soup were introduced as weaning foods. The child was assisted by mechanical ventilation because she sometimes showed respiratory arrest. Cerebrospinal fluid and computed tomography of the brain were normal, and no paroxysmal discharge was found by electroencephalography. Electromyography was not done. Faeces were examined for organisms and toxin of C botulinum. Faeces were suspended in phosphate buffer and centrifuged. Supernatant was diluted in serial tenfold steps and injected intraperitoneally into mice for assay of lethal activity. Colonies grown from the resuspended pellet plated on egg yolk-C welchii or 5% horse blood brain-heart infusion agar were inoculated into cooked meat medium, incubated, and tested for biochemical properties and

toxigenicity.4

Plasma endothelin concentrations during infrarenal aortic

crossclamping.

Faecal supernatant and culture medium had toxin concentrations of 2 x 103 minimum lethal doses (MLD)/ml (6 x 103 MLD/g faeces) and about 10" MLD/ml, respectively. Toxicities were not increased by trypsin treatment, but were inactivated by heat treatment at 80°C for 10 min and neutralised by antiserum against C botulinum type C toxin. Biochemical properties of a representative toxigenic culture were those described for C botulinum type C. 6 weeks after admission faeces contained only 120 MLD/g of toxin, and no type C organisms were found.

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Type C and D strains rarely cause botulism in humans, and no outbreaks of infant botulism have been reported. However, Sonnabend et al5 identified type C organisms and toxin at necropsy in the colon contents of an infant with SIDS. We have found both organisms and toxin in an infant with paroxysmal dyspnea. The patient has survived, but her physical condition is poor, probably because of brain damage caused by hypoxia. We conclude that type C spores can colonise the gut of human infants and cause botulism, even though adult food-borne botulism with type C toxin is rare. Department of Microbiology, Sapporo Medical College, South 1, West 17, Sapporo 060, Hokkaido, Japan

KEIJI OGUMA KENJI YOKOTA SHUNJI HAYASHI

Department of Food Science, Hokkaido Institute of Public Health

KOICHI TAKESHI MITSURU KUMAGAI

Department of Pediatrics, Sapporo Medical College

NOZOMI ITOH NOBUTADA TACHI SHUNZO CHIBA

PUFA and accordingly for eicosanoid products in the cyclooxygenase pathway, might be in favour ofn-6 PUFA in studies with cod liver oil, where cod liver oil has an EPA to linoleic acid (LA, C18:2 n-6) ratio of 3-2. The other fish oils all have higher ratios

(salmon 4-6,maxEPA5’2,andefamed 8-1). Further, dietary fish oils with

a

high EPA content may result in increased plasma peroxide

concentrations, which necessitates a concomitant increased dietary

supplementation of vitamin E.6 Higher OA content (ie, cod liver oil) may,

however, resist oxidative modifications and result in

a

low-density-lipoprotein lowering effect while it simultaneously reduces the progression of atherosclerosis.8 Contradictory results should thus be expected when cod liver oil is used to determine the effect of fish oil. Differences in effect due to the use of different fish oils can be ascribed to variations either in the fatty acid composition of the fish oil or to the glycerol position of EPA. SAMRC Research Institute for Nutritional Diseases, Tygerberg 7505, South Africa

H. Y. TICHELAAR

Dyerberg J, Bang HO, Hjome N. Fatty add composition of the plasma lipids in Greenland Eskimos. Am J Clin Nutr 1975; 28: 958-66. 2. Ackman RG. Some possible effects on lipid biochemistry of differences in the distribution on glycerol of long-chain n-3 fatty adds in the fats of marine fish and 1.

1. Hall

JD, Mccroskey LM, Pincomb BJ, Hatheway CL. Isolation of an organism resembling Clostridium barati which produces type F botulinal toxin from an infant with botulism. J Clin Microbiol 1985; 21: 654-55. 2. Aureli P, Fenicia L, Pasolini B, Gianfranceschi M, Maccroskey LM, Hatheway CL. Two cases of type E infant botulism caused by neurotoxigenic Clostridium butyricum in Italy. J Infect Dis 1986; 154: 207-11. 3. Arnon SS, Darnus K, Chin J. Infant botulism: epidemiology and relation to sudden infant death syndrome. Epidemiol Rev 1981; 3: 45-66. 4. Oguma K, Yamaguchi T, Sudou K, Yokosawa N, Fujikawa Y. Biochemical classification of Clostridium botulinum type C and D strains and their nontoxigenic derivatives. Appl Environ Microbiol 1986; 51: 256-60. 5. Sonnabend OAR, Sonnabend WFF, Krech U, Molz G, Sigrist T. Continuous microbiological and pathological study of 70 sudden and unexpected infant deaths: toxigenic intestinal Clostridium botulinum infection in 9 cases of sudden infant death syndrome. Lancet 1985; i: 237-41.

Eicosapentaenoic acid composition of different fish oil concentrates SIR,-Interest in n-3 polyunsaturated fatty acids (PUFA) as dietary factors was initiated by the Greenland Eskimo diet.1 Care should, however, be taken in extrapolating to non-Eskimos because the Eskimo marine mammal diet contains eicosapentaenoic acid (EPA, C20:5 n-3) and docosahexaenoic acid (DHA, C22:6 n-3) mainly as components of the glycerol 1 and 3 positions in contrast with the 2-position in marine fish oils.2 Much research has been done with different fish oil concentrates, with contradictory results. Both increases and decreases in the linoleic acid (C18:2 n-6) content of plasma lipids are found. Significantly increased high-density-lipoprotein cholesterol levels were noted only with high doses of EPA.3 In some studies cholesterol is lowered by a moderate fish oil intake, while in others increased intake has no effect.4 Triacylglycerol reductions have been found in healthy and in hypertriglyceridaemic individuals.’ Although many studies indicate that dietary supplementation with n-3 PUFA may lower blood pressure, others demonstrate increased blood pressure.6 The EPA content differs in various fish oil concentrates (see table), as does that of oleic acid (OA, C18:1n-9). ’MaxEPA’ should yield similar effects to ’Efamed’, although the EPA content is lower in the former because DHA can be retroconverted in man so that DHA acts as a precursor for EPA biosynthesis. Since DHA is higher in maxEPA, the combined effect of the rapidly formed prostaglandin 13 may yield similar effects to that of efamed.1 Competition for the 6-desaturase enzymes between n-6 and n-3 MEAN PERCENTAGE OF SELECTED FATTY ACIDS IN FOUR FISH OIL CONCENTRATES

marine

mammals. Atherosclerosis 1988; 70: 171-73.

PM, Kinsella JE. Fish oil consumption and decreased risk of cardiovascular disease: a comparison of findings from animal and human feeding trials. Am J Clin

3. Herold

Nutr 1986; 43: 566-98.

Goodnight SH, Harris WS, Connor WE, Illingworth DR. Polyunsaturated fatty acids, hyperlipidemia, and thrombosis. Atherosclerosis 1982: 2: 87-113. 5. Weaver BJ, Holub BJ. Health effects and metabolism of dietary eicosapentaenoic acid. Prog Food Nutr Sci 1988, 12: 111-50. 6. Hornstra G. The significance of fish and fish-oil enriched food for prevention and therapy of ischaemic cardiovascular disease. In: Vergroesen AJ, Crawford M, eds. 4.

The role of fats in human nutrition. London: Academic Press, 1989. 151-235. S, Vischer A, Preac-Mursic V, Weber PC. Dietary docosahexaenoic add is retroconverted in man to eicosapentaenoic add, which can be quickly transformed to prostaglandin I3. Prostaglandins 1987; 34: 367-75. 8. Parthasarathy S, Khoo JC, Miller E, Barnett J, Witztum JL, Steinberg D. Low density lipoprotein rich in oleic acid is protected against oxidative modification: implications for dietary prevention of atherosclerosis. Proc Natl Acad Sci USA 7. Fischer

1990; 87: 3894-98.

Which heart valve? SIR,-Mr Treasure (Nov 3, p 1115) raises important points about the clinical assessment of prosthetic heart valves. The ideal evaluation is the randomised trial but there are obstacles to such studies. Those identified by Treasure include the large numbers required for statistical significance. Many surgeons are reluctant to take part in trials because of deeply felt, if not scientifically proven convictions that they know the best valve for their patient and will not delegate such an important decision to a randomisation envelope. It does seem unlikely that randomised trials of sufficient size will be implemented successfully. However, many excellent centres painstakingly record experience with single-valve series, and these results form the bulk of our knowledge on heart valve substitutes. Single-institution, single-valve series are of limited value for comparative purposes but the problems are not insoluble. Two important limitations are patient-related factors which may affect outcome and a lack of uniformity in the definition of valve-related events. But how important are patient-related variables? Such variables play an important part in survival and function after heart valve replacement, but those are crude indicators, rarely relied upon in the assessment of valve performance. These variables also affect the incidence of other valve-related complications but the impact is smaller than one might expect. Much of the evidence derives from a study by Mitchell et aP in which twenty-nine patient-related variables were analysed for their effect on valve performance. The conclusion was that patient-related factors were more important than valve type but Bain and I in our critical analysis of this study suggested that valve type was the most important determinant of thromboembolism, anticoagulant-related haemorrhage, fatal valve failure, and valve-related mortality and morbidity.2 Patient-related variables do influence some valve-related complications, but the magnitude of this influence depends on the complication-ie, some valve-related complications are more valve-related than others. For instance, our analysis of five valve types3 showed that the incidence