Nightmares, asthma and pindolol.
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Biomedical subjects
Publications and source records attributed to J D England.
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1. The anti-hypertensive actions of timolol and hydrochlorothiazide were analysed in a double-blind 2 x 2 factorial trial in twenty patients with essential hypertension. Each patient went through four phases of 8 weeks in randomized order, receiving timolol alone, hydrochlorothiazide alone, timolol plus hydrochlorothiazide, and placebo. 2. Supine mean arterial pressure fell from 119 mmHg in the placebo phase, to 110 mmHg during the thiazide phase, 106 mmHg during the timolol phase, and to 101 mmHg during the combined timolol plus hydrochlorothiazide phase. 3. Factorial analysis revealed that the hypotensive actions of the beta-receptor-blocking drug and the diuretic were additive, without any synergism or antagonism. 4. Plasma renin activity measured in ng 3 h-1 ml-1 rose from 5-02 in the placebo phase to 9-54 in the diuretic phase, but fell to 1-79 in the beta-receptor blockade. It was unchanged in the combined therapy phase, despite the greater drop in blood pressure. These results suggest that the fall in plasma renin activity during beta-receptor blockade is of little importance in the hypotensive action of beta-receptor-blocking drugs.
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1. The effects of two beta-adrenoreceptor blocking drugs, metoprolol and atenolol, on plasma lipoproteins were studied in thirty-four patients using a single-blind cross-over design, with a 10-day placebo washout period between drugs. 2. Compared with placebo values, neither metoprolol nor atenolol influenced total plasma cholesterol levels, while total plasma triglycerides increased slightly. 3. Low density lipoprotein protein level remained unaltered, while high density lipoprotein (HDL) cholesterol and protein were significantly reduced by both beta-adrenoreceptor blockers. 4. The ratio of total cholesterol to HDL cholesterol was increased by both drugs. 5. The data suggest that patients taking these drugs over many years may be exposing themselves to increased vascular risk, despite other anticipated benefits from such therapy.
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Hemoglobin A1c (HbA1c) was measured as an indicator of glucose control in 180 children and adolescents with diabetes mellitus who received two daily injections of insulin as part of a highly structured treatment program. A total of 426 HbA1c determinations was made in the group of 180 patients. HbA1c values were elevated in most patients despite the aggressive treatment. The HbA1c level was very elevated at diagnosis, fell to near normal after 60-90 days of insulin therapy, increased gradually, and reached a plateau after approximately 4 yr duration (at about twice the level in normal subjects) (mean +/- SEM, 10.0 +/- 0.2% and 5.34 +/- 0.07%, respectively). Mean insulin dose (U/kg/24 h) paralleled both HbA1c and duration of diabetes. The relationship between endogenous insulin secretion and glucose control was examined in those patients with diabetes for longer than 5 yr. Patients were separated into three groups based on HbA1c levels: those with HbA1c less than 9% (N = 22), between 9 and 11% (N = 26), and greater than 11% (N = 28). Serum C-peptide and glucose concentrations were measured 2 h after a standard breakfast in those patients in the "low" and "high" HbA1c groups (mean HbA1c values 8.2% and 12.7%, respectively). C-peptide was detectable in all patients and the mean C-peptide levels did not differ significantly in the two groups, although postprandial glucose concentrations were significantly lower in the "low" HbA1c group (means +/- SEM, 96 +/- 11 and 211 +/- 21 mg/dl, respectively; P less than 0.001).
The frequency of symptomatic hypoglycemia was determined prospectively over an 18-mo period in 147 children and adolescents with diabetes mellitus. All patients were treated with two daily injections of insulin. The data were analyzed to determine the relationship between episodes of symptomatic hypoglycemia and blood glucose control as assessed by hemoglobin A1c measurements. There were 542 patient visits during the study period. During each clinic visit, patients were separated into one of four hypoglycemic categories based on the medical history since the preceding visit. These categories were: no reactions, mild to occasional reactions, mild to frequent reactions, and severe reactions. Reactions were considered severe if they were characterized by altered central nervous system function or prolonged sympathetic nervous system symptoms. Forty-seven percent of the patients reported at least one reaction during the 18-mo study period, but only 4% (i.e., 6 out of 147 patients) reported severe reactions. The mean hemoglobin A1c level was significantly lower in patients who reported reactions than in patients who did not report reactions [hemoglobin A1c values (x +/- SEM) = 7.78 +/- 0.1% vs. 9.48 +/- 0.1%, respectively; P less than 0.001]. The severity of hypoglycemia was inversely related to the degree of altered blood glucose control; episodes of frequent or severe symptomatic hypoglycemia occurred almost exclusively in patients with well-controlled diabetes as reflected in their near-normal hemoglobin A1c levels. There were no significant differences in mean insulin dose/kg, age, or duration of diabetes comparing patients in the four hypoglycemic categories. The results indicate that the hemoglobin A1c level can be a useful clinical guide to identify patients who are most likely to develop serious symptomatic hypoglycemia.