Amoebic Liver Abscess and Indigenous Alcoholic Beverages in the Tropics.

Amoebic liver abscess (ALA) seen commonly in the tropics is predominantly confined to adult males, especially those who consume locally brewed alcohol, although intestinal amoebiasis occurs in all age groups and in both genders. Whether the role of alcohol in the development of ALA is incidental and casual or whether alcohol is causally implicated has been debated. It has been argued that socioeconomic factors and poor sanitary conditions are the primary culprits that casually link alcohol to ALA. However, there has emerged an abundance of data that implicates alcohol in a more causal role in facilitating the extraintestinal invasion of the infective protozoan and the subsequent development of ALA. These factors include the role of alcohol in host immunity, parasitic proliferation, and invasion and in creating a conducive hepatic microenvironment. The contributory role of alcohol-induced increase in hepatic iron stores and lipid content is discussed. Late-stage liver disease with fibrosis seems to be protective for the development of ALA. Further research is necessary to elucidate the many possible mechanisms that predispose to hepatic amoebiasis, so that appropriate individual and population-based preventive measures can be implemented.

Persistent impairment of endothelium-dependent relaxation to acetylcholine and progression of atherosclerosis following 6 weeks of cholesterol feeding in the rabbit.

The synthesis and (or) release of endothelium-dependent relaxant factor released by acetylcholine is impaired in New Zealand white rabbits fed an atherogenic diet. Experiments were designed to investigate whether the synthesis and (or) release of the endothelium-dependent relaxant factor from rabbit aortas are restored after reversal from an atherogenic diet to a non-atherogenic diet. Atherosclerosis was induced by feeding a diet containing lipids and 2% cholesterol for 6 weeks. Rabbits were sacrificed after 6 weeks on the atherogenic diet and 36 weeks after return to a standard laboratory diet. Synthesis and (or) release of the factor from the thoracic aorta was assayed using a bioassay system. The relaxant responses produced in the assay tissue were impaired both in the acute stage and after 36 weeks on non-atherogenic food. This impaired relaxation is probably due to a persistent functional abnormality in the aortic endothelium resulting in the failure to synthesize and (or) release endothelium-dependent relaxation factor 36 weeks after induction of atherosclerosis.

Evolution of the responses to exercise in left ventricular aneurysms after anterior wall acute myocardial infarction.

The evolution of the heart rate, blood pressure and electrocardiographic responses to exercise in 20 patients (group A) who exhibited echocardiographic evidence of left ventricular (LV) aneurysms after acute myocardial infarction (AMI) were examined. The responses were compared with those seen in 19 patients without LV aneurysms who were matched for age, gender and location of infarct (group B). Patients taking beta blockers were excluded from the study. It was found that the heart rate response to exercise was accentuated in group A at the time of discharge from hospital and that it became attenuated over 9 to 12 months. The blood pressure response was significantly increased over 9 to 12 months in group B. Persistence of ST elevation during exercise, 10 to 12 weeks after AMI, was diagnostic of an LV aneurysm. One year after AMI the sensitivity of ST elevation was 90%, specificity was 95% and the negative predictive value 90%.

Absence of effect of calcium antagonists on endothelium-dependent relaxation in rabbit aorta.

The effect of chronic feeding of New Zealand White rabbits with nicardipine (60 mg kg-1 daily for 5 weeks) on the endothelium-dependent relaxation (EDR) to acetylcholine (ACh) was examined in vitro. The effect of acute exposure to nicardipine and diltiazem (10 mumol l-1) in the tissue bath was also examined. A bioassay system for endothelium-dependent relaxation factor (EDRF) in which a rabbit aortic ring with endothelium removed was used as recipient and a segment of rabbit aorta with endothelium as donor (producing EDRF in response to ACh) was developed. This system enabled the effect of nicardipine on the synthesis/release and on the relaxation to EDRF to be studied separately. The maximum relaxations to ACh in control and nicardipine-fed animals were 43.6 +/- 5.5 and 53.8 +/- 6.7% (mean +/- s.e. mean) of the contractile response to noradrenaline (NA, 1 mumol l-1) (n = 6, P greater than 0.05). Similarly the EDR to ACh was not significantly altered by acute exposure (30 min) to nicardipine or diltiazem. The maximum relaxations without and with nicardipine were 32.4 +/- 4.2% and 28.0 +/- 3.1% of the contraction to NA (1 mumol l-1) (n = 11, P greater than 0.05). The corresponding data for diltiazem were 42.1 +/- 5.7 and 36.4 +/- 7.3% respectively (n = 11, P greater than 0.05). Both calcium antagonists inhibited the contraction induced by potassium (100 mmol l-1). Nicardipine and diltiazem in concentrations of 100 mumol l-1 reduced the potassium-induced contraction to 33.0 +/- 9.0% and 53.8 +/- 6.7% of control respectively (n = 6, P less than 0.05). In the bioassay experiments the infusion of nicardipine on (a) the recipient tissue only and (b) the donor and the recipient tissue had no significant effect on the relaxant response observed in the recipient tissue when superfused with Krebs-bicarbonate buffer containing ACh via the donor tissue (n = 6, P greater than 0.05). These results indicate that nicardipine and diltiazem had no significant effect on synthesis/release and the relaxant response to EDRF in the rabbit aorta. Thus the translocation of Ca2+ accompanying the EDR to ACh in the rabbit aorta is likely to utilize Ca2+ channels not blocked by these calcium antagonists.

Endothelium-dependent relaxation and experimental atherosclerosis in the rabbit aorta.

This study was undertaken to determine whether the production or release of the endothelium-dependent relaxatory factor is impaired in atherosclerotic New Zealand White rabbits. Atherosclerosis was induced by feeding a diet containing 2% cholesterol for 6 weeks. The production or release of endothelium-dependent relaxatory factor was assayed as follows. A 5-cm length of aorta donor was perfused with Krebs-bicarbonate buffer and the perfusate drained over a deendothelialized ring of recipient aorta set up for recording isometric tension. The recipient was precontracted with norepinephrine (0.2 mumol/L) in the perfusate. When acetylcholine was added to the perfusate, the recipient relaxed in a dose-dependent manner. This assay was used to compare the relaxatory responses produced in recipient rings by adding acetylcholine to donors from atherosclerotic and control rabbits. The relaxation produced by atherosclerotic donors were smaller than those generated by control donors (16.5 +/- 4.9 vs. 32.7 +/- 5.3%; n = 10, p less than 0.05). It is suggested that in atherosclerotic rabbits the ability of aortic endothelium to produce or release endothelium-dependent relaxatory factor is impaired.

Humoral nature of the urine response to simulation of atrial receptors.

The diuretic response to stimulation of left atrial receptors by distending small balloons located at the pulmonary vein--left atrial junctions and in the left atrial appendage was studied in anaesthetized dogs in which bretylium tosylate, atenolol and atropine had been administered to effect blockade of renal nerves and to prevent increases in heart rate resulting from stimulation of atrial receptors. In these dogs, distension of the balloons was not associated with significant changes in heart rate, left atrial pressure or arterial blood pressure, and resulted in increases in urine flow, decreases in urinary sodium concentration and no significant changes in urinary sodium excretion. It is concluded that the humoral mechanism is responsible for the diuresis in response to stimulation of atrial receptors and has no significant effect on the response of natriuresis known to involve a decrease in the activity in the renal nerves and haemodynamic changes associated with stimulation of atrial receptors.

The role of renal nerves in the diuresis and natriuresis caused by stimulation of atrial receptors.

The diuretic response to stimulation of left atrial receptors by distending balloons located either at the pulmonary vein-left atrial junctions or in the body of the left atrium, was studied in anaesthetized dogs in which on kidney had been surgically denervated. In these dogs diuretic and natriuretic responses to stimulation of atrial receptors were obtained in the denervated and the intact kidney; both responses were significantly greater in the intact kidney than in the denervated kidney. In the denervated kidney the natriuretic response showed a significant correlation to increases in heart rate resulting from stimulating of atrial receptors. It is concluded that the renal nerves contribute significantly to the increases in urine flow and sodium excretion in response to stimulation of atrial receptors. In the denervated kidney, the diuresis appeared to be mediated by a humoral mechanism and the natriuresis was associated with concomitant increases in heart rate.

Long-term comparison of metoprolol and methyldopa in the treatment of hypertension.

The effect of the cardioselective beta-adrenoreceptor blocking compound, metoprolol, was compared with methyldopa in the long-term management of hypertension. Thirty patients given metoprolol and twenty-six given methyldopa were treated for 2 years. The maximum dose of metoprolol was 200 mg twice daily (average 308 mg) and of methyldopa 1,000 mg twice daily (average 1,120 mg). Blood pressure was similar at entry to the study (metoprolol 177/110 mmHg and methyldopa 181/111 mmHg). After 2 years of treatment the blood pressure levels were again similar (metoprolol 149/91 mmHg and methyldopa 148/91 mmHg). Erect pressures were lower in the methyldopa group, but there was no difference between supine and erect blood pressure levels in those on metoprolol. At an exercise load of 300 and 600 kpm the increase in systolic pressure was significantly less in the metoprolol group. The proportional increase in systolic and diastolic pressure in response to a standardized stress situation was reduced by treatment with metroprolol but not by methyldopa. Tolerance to therapy did not develop in either group. The main difference between metoprolol and methyldopa was in the incidence and severity of side effects. Four patients were withdrawn from the metoprolol group. Seventeen were withdrawn from the methyldopa mainly because of side effects including drowsiness, depression, skin rash, and impotence. Six patients on metoprolol and seventeen on methyldopa continued on therapy although side effects were present. It is concluded that metoprolol and methyldopa lower blood pressure to the same extent, but metoprolol is advantageous because of a lower incidence of side effects.

Effect of exercise in hypertension controlled with metoprolol or methyldopa.

1. The adequacy of the control of essential hypertension during exercise was studied in patients whose resting blood pressure had been controlled for 1 year with either metoprolol or methyldopa. 2. Systolic blood pressure increased with exercise in both groups, the increase being significantly less in the metoprolol group than in the methyldopa group.