Efficacy and tolerance of a fixed ratio combination of hydrochlorothiazide, amiloride and timolol, taken before or after food, in the treatment of hypertension.

An open study was carried out in general practice to assess the efficacy and tolerance of a fixed ratio combination of hydrochlorothiazide (25 mg), amiloride (2.5 mg) and timolol (10 mg) in the treatment of patients with mild to moderate hypertension, and to determine if there were any differences in response when medication was taken before or after food. A total of 663 patients was studied and received 1 to 2 tablets once daily for a period of 12 weeks; 322 patients took their medication before and 341 after food. The results showed that there were similar significant reductions in systolic and diastolic blood pressure and in heart rate in both groups, over half of the patients being controlled (less than 90 mmHg diastolic) after 2 weeks and 80% by the end of the study period. Relatively few adverse effects were reported and the incidence during treatment was less than that recorded on entry to the study. There was no evidence to suggest that the timing of drug intake in relation to food had any effect on the efficacy or tolerance of the combination.

Reduced peripheral vascular symptoms in elderly patients treated with alpha-methyldopa--a comparison with propranolol.

A multicentre study of 6-10 weeks duration was performed in 60 ambulant hypertensive patients aged over 60 years to compare the efficacy of methyldopa and propranolol with particular reference to the occurrence of cold extremities and sleep disturbances. Blood pressure was effectively controlled by both drugs being reduced from a mean of 180/108 mmHg to 161/93 with methyldopa and 180/108 to 162/94 with propranolol. More patients treated with methyldopa (74%) achieved the target diastolic blood pressure of 95 mmHg or below compared with those treated with propranolol (58%). Side effects were more frequent in the propranolol group necessitating the withdrawal of four patients from the study. Only one patient on methyldopa was withdrawn. The incidence of cold extremities was significantly greater with propranolol. The occurrence of sleep disturbances was similar in both groups. In this group of elderly patients methyldopa was better tolerated than propranolol.

Protection of prostacyclin-like activity in human plasma-a non-enzymatic mechanism?

1. The rate of decay of the platelet antiaggregatory activity of prostacyclin in plasma and buffer solutions was investigated. 2. Platelet anti-aggregatory activity of prostacyclin was more stable in plasma than in buffer solutions at physiological pH. 3. The rate of decay of this activity increased with an increase in incubation temperature. 4. Preheating of plasma at 65 degrees C led to a marked but not total loss of its ability to "protect" prostacyclin. 5. Incubation of 6-keto prostaglandin F 1 alpha in plasma did not result in the appearance of platelet anti-aggregatory activity; nor did the decay curves of prostacyclin activity indicate the emergence of any new platelet anti-aggregatory activity. 6. Incubation of 6-keto-prostaglandin E1 in plasma did not lead to any loss of its platelet anti-aggregatory activity for prolonged periods. 7. We conclude that the marked prolongation of platelet anti-aggregatory activity of prostacyclin in plasma is not due to its enzymatic conversion into 6-keto-prostaglandin E1 but due to 'protection' of prostacyclin itself. This 'protection' is probably due to an interaction with a plasma protein.

Prostacyclin-like activity in the female rat thoracic aorta and the inferior vena cava after ethinyloestradiol and norethisterone.

1. Female rats were injected with ethinyloestradiol, norethisterone or both compounds for 30 days. Prostacyclin-like activity was measured in the thoracic aorta and inferior vena cava. 2. In the thoracic aorta of rats injected with ethinyloestradiol and ethinyloestradiol/norethisterone, prostacyclin-like activity was significantly increased. Norethisterone alone had no effect. 3. In the inferior vena cava of rats injected with ethinyloestradiol, norethisterone or both compounds, prostacyclin-like activity was not significantly altered. The amount of prostacyclin generated by the inferior vena cava was much lower than that by the aorta. 4. Experimentally induced changes in the vessel wall after the administration of contraceptive steroids must be due to factors other than diminished prostacyclin production.

Instability of cerebral blood-flow in insulin-dependent diabetics.

Cerebral blood-flow (CBF) was measured in 23 insulin-dependent diabetics before and 2--3 h after insulin/breakfast. In 10 of these patients CBF changed significantly during the day, with a significant fall in 9. In 3 patients who had the greatest falls in CBF there was a concomitant sensation of an impending faint. Thus CBF is unstable in insulin-dependent diabetics in contrast to control subjects in who there is little or no variation. Sudden falls in CBF in insulin-dependent diabetics may explain the symptoms of impending faint without hypoglycaemia; such falls would also be relevant to the pathogenesis of strokes in these patients.

The effect of beta-adrenergic receptor blocking drugs on cerebral blood flow.

1 Cerebral blood flow (CBF) was measured by the 133xenon inhalation method in 33 newly-diagnosed hypertensive patients prior to commencing therapy. 2 Blood pressure was treated by using a varying sequence of four different drugs, namely labetalol, metoprolol, oxprenolol and sotalol, each of which is a beta-adrenergic receptor blocking agent, but with differing additional properties. 3 CBF measurements were repeated when blood pressure was controlled. No significant change in CBF was found with any of the four drugs, in contrast to the fall which has been reported when drugs of this type are administered acutely.

Cerebral blood flow in diabetes mellitus: evidence of abnormal cerebrovascular reactivity.

Cerebral blood flow (CBF) was studied at normocapnia and after a challenge with 5% CO2 in 59 diabetic patients and 28 controls. There was a significant age-related decline in CBF in both groups, which suggests that diabetes does not affect the rate of decrease of CBF with age. After CO2 challenge CBF increased in most of the controls; in the patients CBF increased in 23, decreased in 26, and remained stable in 10. Thus the reactivity of cerebral blood vessels in diabetics is altered. Diabetics have diminished cerebrovascular reserve and are thus at increased risk of cerebrovascular disease because they are unable to compensate when necessary with an increased CBF.

Controlled trial of ornithine alpha ketoglutarate (OAKG) in patients with stroke.

A double blind controlled trial of ornithine alpha-ketoglutarate (OAKG) was carried out on 50 patients admitted to the Royal Free and Royal Northern Hospitals, London, suffering from a recent stroke. Significant improvement was found in patients treated with OAKG when examined on the fifth day of therapy as compared to their control cases. The therapy was given for 5 days. When the patients in the treated and the control groups were compared 10 days after the beginning of treatment, there were no differences between the 2 groups. Implications of these findings are discussed.