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Biomedical subjects

F J Zacharias

Publications and source records attributed to F J Zacharias.

At least 19 recordsLinked to original sources

Benefits and potential harm of lowering high blood pressure.

To investigate whether the lower the blood pressure (BP) the better the prognosis for the patient with moderate-to-severe hypertension, an assessment was made of 902 patients who received the beta 1-selective beta-blocker atenolol (median dose 100 mg a day), either alone or with other antihypertensive agents, for up to 10 years (mean 6.1). 91 died, 40 from myocardial infarction, 21 from stroke, and 30 from other causes. Initial BP was a poor predictor of mortality from myocardial infarction, whereas treated systolic blood pressure (SBP) was a strong predictor. There was a J-shaped relation, confined to those with evidence of ischaemic heart disease, between frequency of death from myocardial infarction and treated DBP (phase V); the frequency was lowest at treated DBP of 85-90 mm Hg and rose with treated DBP on either side of this range.

Adolescent

The efficacy and tolerability of antihypertensive treatment based on atenolol in the prevention of stroke and the regression of left ventricular hypertrophy.

Nine hundred and thirty nine moderate to severe hypertensive patients were treated with a combination of atenolol, a beta 1 selective receptor blocker, diuretics and where required, additional vasodilator therapy to achieve adequate blood pressure (BP) control. Patients were followed up for a period of 10.2 years (mean 6.1 years). Amassed clinical exposure amounted to 5465 patient years. Mean BP fell from 183.0 +/- 1.0/109.2 +/- 0.5 mmHg to 145.1 +/- 0.6/89.3 +/- 0.3 mmHg and treatment resulted in a significant regression of the electrocardiographic signs of left ventricular hypertrophy (LVH). Side effects of treatment were consistent with those expected from a regime comprising a combination of a beta 1 selective hydrophilic beta-blocker, diuretics and vasodilators. Reported side effects appeared to diminish with time; were more common in the elderly than in the young and increased in frequency as the dose of atenolol increased. Biochemical disturbance was minimal. Total mortality (n = 91) and mortality from myocardial infarction (n = 40) were positively related to treated systolic blood pressure (SBP). A J-shaped curvilinear relationship between treated diastolic blood pressure (DBP) and death rate from myocardial infarction has been shown. Although the number of deaths from stroke was small (n = 21), there appeared to be a positive relationship with treated DBP: by contrast the data suggest that in the elderly, lowering SBP to below about 140 mmHg might be associated with an increased incidence of death from stroke.

Adolescent

Low mortality from all causes, including myocardial infarction, in well-controlled hypertensives treated with a beta-blocker plus other antihypertensives.

The aim of the present study was to monitor the efficacy of treatment, morbidity and mortality over a 10-year period in 939 moderate to severe hypertensive patients. All patients were treated in the same hypertension clinic with the beta 1-selective agent atenolol, administered either alone or more usually with a diuretic with or without a vasodilator or other agents. Survival rates were compared with predicted survival rates, had the hypertension not been treated, and also with those of a local reference population matched for age and sex. After a mean follow-up time of 6.1 years, mean blood pressure (BP) was significantly lowered from 183/109 to 145/87 mmHg. Biochemical disturbance was minimal. There were 79 withdrawals from treatment, of whom 37 were lost to follow-up. There were 91 deaths on intention to treat. Systolic blood pressure (SBP) on treatment, and not initial BP, was a powerful predictor of mortality. Patients of all age groups with well-controlled SBP were less likely to die, particularly from myocardial infarction, than those with less well controlled SBP (P less than 0.001). However, due to possible J-curve relationships between treated BP and outcome, lowering SBP below 140-150 mmHg in the elderly, and the diastolic blood pressure (DBP) below about 85 mmHg, may not be beneficial. Total mortality and mortality due to myocardial infarction was about 60% [corrected], of predicted level, had a high BP not been treated, being similar to that in a local reference control population (age- and sex-matched). The death rate from stroke was reduced to about 50% of that predicted. Patients who died showed a mean fall in mean serum triglyceride concentration in contrast to the mean increase that occurred in survivors. It is concluded that patients with moderate to severe hypertension who obtain a high level of general health care and optimal control of BP for up to 10 years, experience a significant decrease in total mortality rate and death from myocardial infarction and stroke.

Adolescent

Adverse reactions to practolol: some observations on the possible relevence to immune mechanisms.

HLA antigen frequencies were determined in patients who had suffered adverse reaction to the beta-adrenergic blocking agent, practolol. No statistically significant differences were observed between these patients and control groups. The latter were selected to include two separate groups, normal random healthy population controls, and controls who had taken practolol with no apparent adverse effects. Patients suffering from the very severe form of reaction, sclerosing peritonitis, were analysed separately from those with other lesion e.g. ocular symptoms, but did not show any significant differences. Altered HLA antigen frequencies were observed for those control patients whose primary diagnosis was hypertension but this was considered to be due to selection bias.

Epitopes

Patient acceptability of propranolol and the occurence of side effects.

The incidence of adverse effects is reported in a group of more than 400 patients treated with propranolol between 1964 and 1974. Severe side effects necessitating withdrawal of the drug were found in less than 10%; dose-limiting side effects were found in less than 15%. Tolerable side effects are studied in detail. Pharmacologically based side effects are recorded and ways of minimizing their frequency are discussed. The acceptability of propranolol in general terms and its advantages are assessed.

Bronchial Spasm