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PULMONARY FAT ACCUMULATION IN PRETERM INFANTS
441 COMPLEMENT FIXING ANTIBODY TO C. JEJUNI IN POULTRY AND MEAT PROCESS WORKERS
OXYFEDRINE AS AN ANTIANGINAL AGENT
SIR,—Your editorial on oxyfedrine (Jan. 3, p. 25) draws attention possible differences between the effects of a drug when given once and when administered long-term. You suggest that such differences might in some way explain the antianginal action of oxy-
to
*Employed by Ministry of Agriculture, Fisheries and Food. groups of people who have a potential occupational contact with C. These included workers who process ducks, chickens, and cattle for human consumption (see table). The prevalence of antibody amongst these individuals is much higher than that in the normal population and approaches the level we found in people who were subject to periodic C. jejuni enteritis because of regular consumption of unpasteurised milk.
jejuni.
Public Health
Laboratory,
Withington Hospital,
D. M. JONES
Manchester M20 8LR
D. A. ROBINSON
PULMONARY FAT ACCUMULATION IN PRETERM INFANTS
SIR,—Levene et al.described intracapillary fat globules and lipid filled macrophages in the lungs of eight very ill low birthweight preterm infants who had been treated with ’Intralipid’ infusion before death. Despite the fact that the lungs of control infants who had not been treated with intralipid were not examined histologically, these workers incriminate intralipid as being associated with the pulmonary fat accumulation. We have investigated twenty-four infants with a birthweight below 1500 g (mean 1040, range 540-1440) born after 28-31 weeks’ gestation who have died in our department within the last 2 -5years. Permission for necropsy was refused in one case and in two infants the lung material was unsuitable for histological examination. The remaining twenty-one infants had a variety of conditions commonly seen in premature babies (perinatal asphyxia, hyaline membrane disease, septicaemia, intracranial haemorrhage, apnoea, patent ductus arteriosus, and necrotising enterocolitis), a pattern similar to that in Levene’s series. The lungs were examined histologically after lipid staining (oilred 0) by one of us (LT.) without prior knowledge of the clinical condition or treatment of the infants. Nine of the twenty-one infants had been treated with intralipid for an average of 5 days (range 1-27) and had received I - .77±0.74 g/kg in 24 h. The other twelve infants had been fed mother’s milk and intravenous carbohydrate solutions but not intralipid. The results (see table) show that pulmonary fat accumulation in very low birthweight infants is not caused by intralipid infusion per se but may be accentuated by intralipid infusion. We cannot explain the pulmonary fat accumulation in the infants who had not received
intralipid. Neonatal Department and Department of Children’s
Pathology.
Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark
G. E. ANDERSEN J. HERTEL I. TYGSTRUP
fedrine. It is difficult to understand how prolongation of the duration of the cardiac muscle action potential can account for a therapeutic effect in patients with angina. Such an effect may indicate a possible antiarrhythmic action (although even this is not fully proven) but has it anything to do with the relationship between myocardial oxygen supply and demand? Surely there is a simpler explanation for the recent promising reports from Northwick Park. 1,2 Oxyfedrine is not, as your editorial suggests, simply a &bgr;-adrenoceptor agonist. It is a partial agonist at these receptors and could be accurately described as a &bgr;-adrenoceptor blocking drug with marked intrinsic sympathomimetic activity. This effect can be demonstrated after acute, single-dose administration. However, it is an
intriguing question as to whether, on prolonged administration,
the drug loses agonist properties whilst retaining blocking properties at &bgr;-adrenoceptors. When administered orally to cats for three to four weeks there is clear evidence of &bgr;-adrenoceptor blockade (shift to the right of isoprenaline dose-response curves) although myocardial contractility and output are maintained.3 It would be of interest to determine just how much &bgr;-blockade is present after prolonged oral administration to patients with angina. There are other properties of oxyfedrine which are more likely to explain any beneficial effect in angina pectoris. In anaesthetised dogs it markedly increases blood flow through the acutely ischaemic myocardium and in fact is the most active drug we have examined in this respect.4 There are significant (and dose-related) decreases in left ventricular filling pressure and volume which are not entirely accounted for by the increased myocardial contractility. There is an additional action of the drug which, if it happened in patients, would certainly be very valuable in anginal therapy. This is a peripheral venodilator action, rather like that of nitroglycerin. In dog isolated saphenous veins oxyfedrine is just as active as nitroglycerin (the venodilator par excellence) at relaxirig noradrenaline-reduced contractions of the circularly arranged smooth muscle. This might suggest that the reduction in leftventricular end-diastolic pressure observed when oxyfedrine is administered to laboratory animals with myocardial ischaemia is due to a combination of myocardial stimulation and a peripheral venodilator action, both, incidentally, properties possessed by nitroglycerin.This would adequately explain the beneficial effects obtained by Whittington and Raftery. 1,2 It would seem important to determine whether these effects are obtained when therapeutic doses of the drug are given to patients with angina. Does it reduce (or prevent) the abnormal increase in left ventricular filling pressure, and the production of myocardial lactate, which occur during exercise in patients with classical angina? Does it have a dilator effect on human peripheral veins which might contribute to a reduction in left ventricular filling pressure? It seems that answers to these questions, and further controlled clinical trials in patients with angina, are needed before this fascinating compound can be fully welcomed into the family of effective antianginal drugs. Department of Physiology and Pharmacology, Royal College, University of Strathclyde, Glasgow
J. R. PARRATT
Whittington J, Raftery EB. A controlled comparison of oxyfedrine, isosorbide dinitrate and placebo in the treatment of patients suffering attacks of angina pectoris. Br J Clin Pharmacol 1980; 10: 211-16. 2. Whittington J, Raftery EB. Oxyfedrine and propranolol: a controlled trial in angina pectoris. Br J Clin Pharmacol 1980; 10: 439-42. 3. Parratt JR. The haemodynamic effects of prolonged oral administration of oxyfedrine, a partial agonist at &bgr;-adrenoceptors: Comparison with propranolol. Br J Pharmacol 1.
1 Levene
MI, Wigglesworth JS, Desai R Pulmonary fat accumulation after ’Intralipid’ infusion m the preterm infant. Lancet 1980; ii: 815. LIPID STAINING OF LUNGS
1974, 51: 5-13. RJ, Parratt JR. Drug-induced changes in blood flow in the acutely ischaemic canine myocardium: Relationship to subendocardial driving pressure. Clin Exp Pharmacol Physiol 1974; 1: 99-112. 5. Parratt JR, Mackenzie JE. Possible mechanisms of action of oxyfedrine as an antiangmal drug. Br J Clin Pharmacol (in press). 6. Editorial. Nitroglycerin: the first one hundred years. Lancet 1979, ii 1340-41
4. Marshall
OXYFEDRINE AS AN ANTIANGINAL AGENT
SIR,—Your editorial on oxyfedrine (Jan. 3, p. 25) draws attention possible differences between the effects of a drug when given once and when administered long-term. You suggest that such differences might in some way explain the antianginal action of oxy-
to
*Employed by Ministry of Agriculture, Fisheries and Food. groups of people who have a potential occupational contact with C. These included workers who process ducks, chickens, and cattle for human consumption (see table). The prevalence of antibody amongst these individuals is much higher than that in the normal population and approaches the level we found in people who were subject to periodic C. jejuni enteritis because of regular consumption of unpasteurised milk.
jejuni.
Public Health
Laboratory,
Withington Hospital,
D. M. JONES
Manchester M20 8LR
D. A. ROBINSON
PULMONARY FAT ACCUMULATION IN PRETERM INFANTS
SIR,—Levene et al.described intracapillary fat globules and lipid filled macrophages in the lungs of eight very ill low birthweight preterm infants who had been treated with ’Intralipid’ infusion before death. Despite the fact that the lungs of control infants who had not been treated with intralipid were not examined histologically, these workers incriminate intralipid as being associated with the pulmonary fat accumulation. We have investigated twenty-four infants with a birthweight below 1500 g (mean 1040, range 540-1440) born after 28-31 weeks’ gestation who have died in our department within the last 2 -5years. Permission for necropsy was refused in one case and in two infants the lung material was unsuitable for histological examination. The remaining twenty-one infants had a variety of conditions commonly seen in premature babies (perinatal asphyxia, hyaline membrane disease, septicaemia, intracranial haemorrhage, apnoea, patent ductus arteriosus, and necrotising enterocolitis), a pattern similar to that in Levene’s series. The lungs were examined histologically after lipid staining (oilred 0) by one of us (LT.) without prior knowledge of the clinical condition or treatment of the infants. Nine of the twenty-one infants had been treated with intralipid for an average of 5 days (range 1-27) and had received I - .77±0.74 g/kg in 24 h. The other twelve infants had been fed mother’s milk and intravenous carbohydrate solutions but not intralipid. The results (see table) show that pulmonary fat accumulation in very low birthweight infants is not caused by intralipid infusion per se but may be accentuated by intralipid infusion. We cannot explain the pulmonary fat accumulation in the infants who had not received
intralipid. Neonatal Department and Department of Children’s
Pathology.
Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark
G. E. ANDERSEN J. HERTEL I. TYGSTRUP
fedrine. It is difficult to understand how prolongation of the duration of the cardiac muscle action potential can account for a therapeutic effect in patients with angina. Such an effect may indicate a possible antiarrhythmic action (although even this is not fully proven) but has it anything to do with the relationship between myocardial oxygen supply and demand? Surely there is a simpler explanation for the recent promising reports from Northwick Park. 1,2 Oxyfedrine is not, as your editorial suggests, simply a &bgr;-adrenoceptor agonist. It is a partial agonist at these receptors and could be accurately described as a &bgr;-adrenoceptor blocking drug with marked intrinsic sympathomimetic activity. This effect can be demonstrated after acute, single-dose administration. However, it is an
intriguing question as to whether, on prolonged administration,
the drug loses agonist properties whilst retaining blocking properties at &bgr;-adrenoceptors. When administered orally to cats for three to four weeks there is clear evidence of &bgr;-adrenoceptor blockade (shift to the right of isoprenaline dose-response curves) although myocardial contractility and output are maintained.3 It would be of interest to determine just how much &bgr;-blockade is present after prolonged oral administration to patients with angina. There are other properties of oxyfedrine which are more likely to explain any beneficial effect in angina pectoris. In anaesthetised dogs it markedly increases blood flow through the acutely ischaemic myocardium and in fact is the most active drug we have examined in this respect.4 There are significant (and dose-related) decreases in left ventricular filling pressure and volume which are not entirely accounted for by the increased myocardial contractility. There is an additional action of the drug which, if it happened in patients, would certainly be very valuable in anginal therapy. This is a peripheral venodilator action, rather like that of nitroglycerin. In dog isolated saphenous veins oxyfedrine is just as active as nitroglycerin (the venodilator par excellence) at relaxirig noradrenaline-reduced contractions of the circularly arranged smooth muscle. This might suggest that the reduction in leftventricular end-diastolic pressure observed when oxyfedrine is administered to laboratory animals with myocardial ischaemia is due to a combination of myocardial stimulation and a peripheral venodilator action, both, incidentally, properties possessed by nitroglycerin.This would adequately explain the beneficial effects obtained by Whittington and Raftery. 1,2 It would seem important to determine whether these effects are obtained when therapeutic doses of the drug are given to patients with angina. Does it reduce (or prevent) the abnormal increase in left ventricular filling pressure, and the production of myocardial lactate, which occur during exercise in patients with classical angina? Does it have a dilator effect on human peripheral veins which might contribute to a reduction in left ventricular filling pressure? It seems that answers to these questions, and further controlled clinical trials in patients with angina, are needed before this fascinating compound can be fully welcomed into the family of effective antianginal drugs. Department of Physiology and Pharmacology, Royal College, University of Strathclyde, Glasgow
J. R. PARRATT
Whittington J, Raftery EB. A controlled comparison of oxyfedrine, isosorbide dinitrate and placebo in the treatment of patients suffering attacks of angina pectoris. Br J Clin Pharmacol 1980; 10: 211-16. 2. Whittington J, Raftery EB. Oxyfedrine and propranolol: a controlled trial in angina pectoris. Br J Clin Pharmacol 1980; 10: 439-42. 3. Parratt JR. The haemodynamic effects of prolonged oral administration of oxyfedrine, a partial agonist at &bgr;-adrenoceptors: Comparison with propranolol. Br J Pharmacol 1.
1 Levene
MI, Wigglesworth JS, Desai R Pulmonary fat accumulation after ’Intralipid’ infusion m the preterm infant. Lancet 1980; ii: 815. LIPID STAINING OF LUNGS
1974, 51: 5-13. RJ, Parratt JR. Drug-induced changes in blood flow in the acutely ischaemic canine myocardium: Relationship to subendocardial driving pressure. Clin Exp Pharmacol Physiol 1974; 1: 99-112. 5. Parratt JR, Mackenzie JE. Possible mechanisms of action of oxyfedrine as an antiangmal drug. Br J Clin Pharmacol (in press). 6. Editorial. Nitroglycerin: the first one hundred years. Lancet 1979, ii 1340-41
4. Marshall