1449
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.
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.
