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Biomedical subjects

A Distler

Publications and source records attributed to A Distler.

At least 181 records · Page 10Linked to original sources

Double-blind comparison of the cardioselective beta-blockers bisoprolol and atenolol in hypertension: the Bisoprolol International Multicenter Study (BIMS).

The antihypertensive efficacy and tolerability of bisoprolol and atenolol were compared in the Bisoprolol International Multicenter Study (BIMS). In 104 patients with essential hypertension (21 to 70 years of age and diastolic blood pressures (DBP) of 100-120 mm Hg in the sitting position), after a four-week placebo period, the active drug was given in a random double-blind crossover design (10 to 20 mg bisoprolol, 50 to 100 mg atenolol) for eight weeks each, with a 2 to 6 week placebo wash-out phase between active therapy. All blood pressures were recorded 24 h after drug intake. Of the 104 patients, 10 were withdrawn during the study because of unwanted effects, unsatisfactory blood pressure response, or intercurrent disease, leaving 94 for intraindividual comparisons. After 8 weeks active treatment with individually titrated dose, there were slightly, but significantly greater falls in blood pressure with bisoprolol (p less than or equal to 0.05). Diastolic target pressures of less than or equal to 95 mm Hg were reached in 68% with bisoprolol and 56% with atenolol (p less than or equal to 0.05; Mc Nemar). There was no between treatment group difference in the patients' self-assessed well-being. For both drugs, response rates were greater in patients below the age of 60 years than in those above 60 years. Better antihypertensive responses were observed with bisoprolol in patients regularly smoking cigarettes.

Adrenergic beta-Antagonists↗

Antihypertensive and metabolic effects of diltiazem and nifedipine.

The antihypertensive effect of diltiazem (180-270 mg/day) and nifedipine (40-60 mg/day) in slow-release forms was assessed over 8 weeks in a double-blind parallel study in 40 subjects with essential hypertension at rest and during exercise. Blood pressure was comparably reduced in both groups at rest as well as during exercise. The responder rates (greater than or equal to 10% reduction in diastolic blood pressure) after 8 weeks of therapy were 53% at rest and 75% during exercise in the diltiazem group and 78% and 50%, respectively, in the nifedipine group. Diltiazem decreased heart rate by 8% (p less than 0.01), while nifedipine did not affect it. As a consequence, myocardial oxygen consumption, as judged by the pressure-rate product, was reduced by diltiazem. Resting plasma norepinephrine levels were increased significantly after 8 weeks of diltiazem therapy. Plasma epinephrine, renin, aldosterone, glucose, insulin, and lactate and routine laboratory parameters were unchanged at the end of the study. No significant changes in total cholesterol and triglyceride levels were observed after 8 weeks. Whereas therapy with diltiazem resulted in an 8% fall in low density lipoprotein cholesterol after 8 weeks (p less than 0.05), nifedipine induced a drop in very low density lipoprotein cholesterol (p less than 0.05) after 8 weeks of therapy. We conclude that both diltiazem and nifedipine are effective antihypertensive agents lacking undesirable metabolic side effect. Diltiazem, however, had the advantage of lowering heart rate and myocardial oxygen consumption.

Adult↗

Humoral and blood pressure effects of the angiotensin converting enzyme inhibitor ramipril in essential hypertension.

The humoral and antihypertensive activities of the angiotensin converting enzyme (ACE) inhibitor 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S, 3S, 5S)-2-azabicyclo[3.3.0] octane-3-carboxylic acid (ramipril, Hoe 498) were investigated in 10 patients with essential hypertension (WHO stage I or II). After a 7-day placebo period, the patients were treated with 5 mg ramipril orally once daily for 14 days. Peak serum concentrations of the active metabolite M1 (dicarboxylic acid) of 5.4-62.0 ng/ml were observed 2-6 h after the first oral dose. The maximum ACE inhibition of 95% was reached 2-4 h after the first oral dose, inhibition exceeded 70% 24 h after dosing. The maximum drop in the systolic and diastolic blood pressure (random zero sphygmomanometer) was measured 4 h after ramipril (p less than 0.02, p less than 0.01), but blood pressure on days 7 and 14 of the treatment period was not different from pretreatment values. Automatically recorded blood pressure results showed a marked reduction of both systolic and diastolic blood pressure during treatment compared to placebo. No side effects occurred. From the present data it is concluded that ramipril is a potent ACE inhibitor in hypertensive patients and that further controlled studies are required for the evaluation of the antihypertensive effect of 5 mg ramipril in essential hypertension.

Adult↗

Free intracellular calcium in essential hypertension. Effects of nifedipine and captopril.

The acute effects of nifedipine (20 mg sublingually) and of captopril (12.5 mg orally) on blood pressure and on platelet intracellular free calcium were investigated in 11 and 12 patients, respectively, with essential hypertension. Platelet calcium was measured by the Quin 2 method. Application of both drugs resulted in a significant fall in blood pressure within 60 min. Platelet calcium, however, was lowered by nifedipine only. There was no correlation between blood pressure reduction and changes in platelet calcium. Platelet intracellular free calcium concentration was 99 +/- 3 nmol in 30 normotensive subjects and 109 +/- 5 nmol (+/- s.e.m.) in 26 patients with essential hypertension (P < 0.05). There was a wide overlap between the values of normotensives and hypertensives. Thus there is no positive evidence of an increased platelet intracellular free calcium concentration in a large proportion of patients with essential hypertension.

Adult↗

Intracellular free calcium and ionized plasma calcium during mineralocorticoid-induced blood pressure increase in man.

Intracellular free calcium is considered to play a key role in vascular smooth muscle contraction. Platelet-free intracellular and plasma total and ionized calcium were assessed during mineralocorticoid-induced blood pressure increase in eight normotensive subjects receiving 0.8 mg fludrocortisone per day for 6 weeks. Blood pressure rose within 1 week and showed a further increase up to the 6th week. Plasma noradrenaline and renin activity (PRA) showed a decrease after 1 week and remained suppressed throughout the study. Ionized plasma calcium fell during mineralocorticoid treatment without any significant changes in total plasma calcium. Intracellular free calcium markedly increased after 1 week and decreased towards control levels thereafter. Previous studies have shown that after 1 week of fludrocortisone administration total peripheral resistance is still normal or even subnormal, whereas it is increased after 6 weeks. Therefore, the initial increase in intracellular free calcium, if also present in arteriolar smooth muscle cells, does not appear to be directly related to the final elevation of total peripheral resistance.

Adolescent↗

Specific alpha-adrenoceptor-mediated vasoconstriction in human veins and interaction with the calcium entry blockers nifedipine and diltiazem.

In order to characterize the pharmacological properties of post-junctional alpha-adrenoceptors, the vasoconstricting effects of the non-specific alpha-adrenoceptor agonist noradrenaline, of the specific alpha 1-adrenoceptor agonist phenylephrine and of the specific alpha 2-adrenoceptor agonist azepexole and the interaction with the calcium entry blockers nifedipine and diltiazem were studied in hand veins of eight healthy volunteers. Both subtypes of alpha-adrenoceptors could be demonstrated in human hand veins in vivo. The alpha 1-subtype seemed to prevail. Vasoconstriction induced by stimulation of either post-synaptic alpha 1- or alpha 2-adrenoceptors was reduced by the calcium entry blockers diltiazem and nifedipine.

Adult↗

Sympathetic tone and pressor response to noradrenaline during mineralocorticoid-induced blood pressure rise in man.

To gain insight into the role of the sympathetic nervous system in the development of mineralocorticoid hypertension, we determined noradrenaline and adrenaline in plasma and urine before, during and after administration of the synthetic steroid, fludrocortisone, for a period of 6 weeks in normotensive volunteer subjects. In addition, pressor reactivity to exogenous noradrenaline, platelet alpha 2- and lymphocyte beta 2-receptors, and platelet intracellular free calcium were determined. Fludrocortisone induced a fall in free and sulpho-conjugated plasma noradrenaline and after 6 weeks, a rise in free and sulpho-conjugated noradrenaline excretion. The number of alpha 2- and beta 2-adrenergic binding sites decreased. A marked increase in platelet free intracellular calcium was found after the first week of fludrocortisone administration followed by a decrease in the following weeks. Reactivity to exogenous noradrenaline was found to be enhanced and this could be a factor contributing to the development of hypertension. Whereas the decrease in plasma noradrenaline observed would suggest a diminution in sympathetic tone, the finding of a rise in urinary noradrenaline excretion after 6 weeks of steroid administration in the presence of suppressed plasma levels points to an increased renal sympathetic drive. The decreased number of platelet alpha 2- and lymphocyte beta 2-receptors observed would also be consistent with the assumption of an increased sympathetic tone.

Adult↗

Does captopril reduce renal function in renovascular disease by postglomerular vasodilatation?

In hypertensive patients with bilateral renal artery stenosis (RAS) or RAS of a solitary kidney, reversible decrease of glomerular filtration rate (GFR) or acute renal failure has been observed following captopril administration. Decrease of GFR has been ascribed to preferential efferent vasodilatation. To test this hypothesis, acute changes of mean arterial pressure (MAP), renal plasma flow (RPF), GFR, plasma renin activity (PRA) and PGE2-excretion after 50 mg captopril orally were measured in post-transplant hypertensives with and without transplant renal artery stenosis (TRAS) during treatment with diuretics. The fall in MAP was similar in both groups; RPF did not change significantly; GFR decreased from 58 +/- 14 (s.d.) to 49 +/- 14 ml/min (TRAS, n = 8) and from 60 +/- 15 to 50 +/- 16 ml/min (without TRAS, n = 8). There was no evidence of postglomerular dilatation in patients with TRAS, and filtration fraction decreased only in patients without TRAS. Increase of PRA after captopril was not significantly different between the two groups. PGE2-excretion did not change significantly. In one patient with severe TRAS, long term angiotensin converting enzyme (ACE) inhibition and acute normalization of MAP with sodium nitroprusside both induced a comparable decrease of GFR. The results demonstrate that acute postglomerular vasodilatation does not necessarily occur after ACE inhibition in patients with TRAS and a high-renin state.

Captopril↗

Compliance with salt restriction as a limiting factor in the primary prevention of hypertension.

It is an important but still unresolved question whether reduction of salt intake in the offspring of hypertensives (a high risk group) prevents the development of the disease. Therefore, 178 offspring (14-26 years old) of hypertensives were enrolled in a 2-year pilot trial aimed mainly at a reduction in salt consumption. For the intervention group (n = 99) a behavioural approach was chosen with extensive counselling by experienced dietitians. The controls (n = 79) received no continuous dietary advice. Both groups showed a small decline in sodium intake over time, but the differences between the two groups were not significant. Division into subgroups with and without sodium reduction revealed no differences in blood pressure. We conclude that the inherent resistance to any change of lifestyle among healthy subjects may require new and more comprehensive motivational approaches.

Adolescent↗

[Carpal tunnel syndrome, a late complication in chronic hemodialysis].

145 patients on haemodialysis for 1 month to 16 years were examined for carpal tunnel syndrome. Typical signs and symptoms of the syndrome, mostly in both hands but more pronounced on one side, were seen in 21 patients (15%). In these cases carpal tunnel syndrome was frequently (19%) accompanied by Raynaud's phenomenon of the digits supplied by the median nerve. There was a significant correlation between the incidence of carpal tunnel syndrome and the duration of dialysis. The association of carpal tunnel syndrome with analgesic nephropathy was significantly higher than with other kidney diseases. Immediate relief of pain was achieved after carpal tunnel release in eight patients (11 hands). Sensory and motor function was gradually, but often only partially, restored. Unoperated carpal tunnel syndrome progressed to loss of sensory and motor function within 1 to 4 years after onset of symptoms. Carpal tunnel syndrome should be considered an important late complication of chronic haemodialysis.

Adult↗

[Trial for digitalis withdrawal in hemodialysis patients].

The indication for digitalis treatment was investigated in a controlled and prospective study lasting 12 months in 110 patients on long-term haemodialysis. In ten patients, digitalis was needed because of tachyarrhythmia due to atrial fibrillation and in five because of recurrent pulmonary edema. In 57 patients receiving digitoxin, therapy was discontinued for 4 to 6 weeks, whereas 13 patients not yet treated with digitalis, received digitoxin for 4 weeks. Without digitoxin, trial fibrillation occurred in 4 patients, while no patient experienced atrial fibrillation with digitoxin (P = 0.002). In 13 patients, radiological findings (heart enlargement, pulmonary congestion) were better with digitoxin than without. Thus digitoxin appeared to be clearly indicated in 29% of the haemodialysed patients. Additionally, digitalis was indicated in 31 patients because of heart enlargement, pulmonary congestion and (or) previous pulmonary edema. Initially, 76% of the patients were receiving digitoxin, whereas, after the investigation, the rate was only 57% (P less than 0.001). The prospective frequency of clinically apparent digitoxin intoxication was low (3%) and so were the overall toxic plasma digitoxin levels (5%). Digitalis should be given deliberately but not restrictively to haemodialysis patients, since atrial fibrillation (13%) and heart failure (50%) are frequent and often concealed.

Adult↗

Crossover comparison of nitrendipine with propranolol in patients with essential hypertension.

The antihypertensive effect of nitrendipine (2 X 10 to 2 X 20 mg/day) was compared with that of propranolol (2 X 80 to 2 X 160 mg/day) in a randomized crossover study. Twenty-five patients were treated over two 4-week periods following a placebo period of 2 weeks. Three patients dropped out of the study because of side-effects (two on nitrendipine and one on propranolol). Arterial pressures decreased in a comparable manner from 171/107 mm Hg (measured in a sitting position) to 147/91 mm Hg after 4 weeks on nitrendipine and to 145/93 mm Hg after 4 weeks on propranolol. The frequency of side-effects possibly related to treatment was comparable for both drugs, but decreased with the duration of therapy with nitrendipine only. The antihypertensive effect of nitrendipine, but not of propranolol, correlated positively with age and plasma noradrenaline.

Adult↗

Effect of nifedipine and verapamil on alpha-receptor-activation in patients with essential hypertension.

The question of whether the hypotensive effect of calcium entry blockers involves an interaction with alpha-adrenergic receptors was examined. The effect of nifedipine subl. (20 mg, n = 9) and of verapamil p.o. (160 mg, n = 9) on the pressor effect of the unselective alpha-adrenergic agonist noradrenaline, as well as on 3H-yohimbine binding to platelet alpha 2-adrenoceptors was studied in patients with essential hypertension. In addition, the effect of nifedipine on reactivity to the selective alpha 1-adrenergic agonist phenylephrine was investigated (n = 9). Nifedipine caused a significant reduction of reactivity to noradrenaline (P less than 0.01), along with a significant decrease in binding sites (P less than 0.01). Affinity to the alpha 2-receptors was unchanged. Verapamil, although equally effective in lowering blood pressure, had no effect on the pressor response or binding sites. The pressor effect of the alpha 1-agonist phenylephrine was reduced (P less than 0.01) by nifedipine. Nifedipine may therefore affect both alpha 1- and alpha 2-adrenoceptors in patients with essential hypertension. Since verapamil did not affect the pressor response to noradrenaline or yohimbine-binding, the interaction with alpha 2-adrenoceptors does not appear to be a general prerequisite for the hypotensive action of calcium entry blockers.

Adult↗

Carpal tunnel syndrome: a major complication in long-term hemodialysis patients.

One hundred and forty-five patients on hemodialysis for periods of 1 month to 16 years were examined clinically for carpal tunnel syndrome (CTS). Typical symptoms and clinical manifestations of symptomatic CTS, either unilaterally or in both hands, were detected in 21 of these patients (15%). In contrast to the classic form of CTS, hemodialysis CTS in our patients was frequently accompanied by Raynaud's phenomenon of those digits supplied by the median nerve. A highly significant correlation was established between the incidence of CTS and the duration of dialysis (p less than 0.001). The association of CTS with analgesic nephropathy was significantly higher (52%) than with other kidney diseases (p less than 0.034). Immediate relief of pain was achieved after carpal tunnel release (11 releases) in 8 of the 21 patients. Sensory and motor function was gradually, but often only partially, restored. Unoperated CTS progressed to loss of sensory and motor function within 1 to 4 years after the onset of symptoms. CTS should be considered a major late complication in patients on chronic hemodialysis.

Adult↗