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Biomedical subjects

P Weidmann

Publications and source records attributed to P Weidmann.

At least 199 records · Page 11Linked to original sources

[Prognostic factors in percutaneous transluminal dilatation of the renal arteries in renovascular hypertension].

In 59 percutaneous transluminal dilatations (PTD) the coaxial double catheter system was chiefly used, and only in one case was the axillary approach necessary. Clinically relevant complications were 1 dissection of the dilated renal artery (re-dilated successfully) and 2 hemorrhages at the femoral puncture site (1 surgical repair). In 32 patients (follow-up 2-52 months, mean 20 months) blood pressure was lowered from 187/108 to 150/91 mm Hg despite reduced antihypertensive therapy (p less than 0.001). Out of 15 patients with atherosclerotic stenoses blood pressure was normalized by PTD in 2 cases (unilateral) and improved in another 8 cases. Out of 11 patients with fibromuscular dysplasia blood pressure was normalized in 7 cases (all unilateral), improved in 3 and unchanged in 1 (bilateral). Among 6 patients with miscellaneous disease (vasculitis, renal insufficiency) only 2 were improved. Thus, PTD of renal arteries is a useful alternative in the management of renovascular hypertension, mainly in patients with fibromuscular dysplasia, unilateral stenosis and elevated renal vein renin ratio. Long-term results are comparable to the surgical results. However, since no surgical dissection is necessary, morbidity is low and long and costly hospital stays can be avoided. The procedure can be repeated in relapsing cases. For rare complications a vascular surgery team should be available.

Adult↗

Metoclopramide alone or combined with flurbiprofen in the treatment of orthostatic hypotension associated with diabetes mellitus.

Two patients with orthostatic hypotension, complicating diabetes mellitus, were treated with dopaminergic antagonist metoclopramide alone or combined with the nonsteroidal anti-inflammatory agent flurbiprofen. Both patients responded favorably to combined treatment of both drugs, with improvement of orthostatic hypotension. In one case, this improvement persisted after withdrawal of flurbiprofen on metoclopramide monotherapy. Blood volume and plasma aldosterone, norepinephrine, and epinephrine levels were unaltered during treatment with these agents. However, plasma renin activity was markedly decreased and, in one patient, exchangeable sodium was increased by 250 mmol. Metoclopramide, alone or combined with the nonsteroidal agent flurbiprofen, may be useful in the treatment of postural hypotension associated with diabetes mellitus. The favorable influence of these agents on blood pressure could not be explained by blood volume expansion or activation of the sympathetic or renin-angiotensin-aldosterone systems.

Catecholamines↗

Total plasma clearance of infused norepinephrine in non-azotemic diabetes mellitus.

The total plasma clearance of norepinephrine (NE) was assessed during steady state NE infusion at two different dose rates in 27 patients with non-azotemic diabetes mellitus as compared with 27 normal subjects. Lower NE dose rates were required in diabetics than in normal subjects (P less than 0.001) to induce similar increases in blood pressure. However, plasma NE levels during NE infusion correlated closely (r = 0.79 and 0.78; P less than 0.001) with concomitant dose rates, and this relationship was similar in both study groups. Moreover, the plasma NE clearance did not differ between low and high dose rates of NE infusion, and was similar in diabetics and normal subjects (6.0 +/- 3.1 and 5.1 +/- 2.6 liter/min, respectively). It correlated inversely with the pre-infusion plasma NE (r = -0.38 and -0.53; P less than 0.05);this relationship was also similar in the two groups. The correlation relating plasma NE to NE infusion rates as well as the plasma NE clearance did not differ between the 13 diabetics without and the 14 with signs of peripheral neuropathy or between the 17 patients with normal and the 10 patients with high blood pressure. These findings suggest that the kinetics of circulating NE are usually unaltered in non-azotemic diabetes mellitus. An increased pressor responsiveness to NE, in the presence of normal plasma NE concentrations and clearance rates, may be a setting predisposing for the development of hypertension in diabetic patients.

Adult↗

Effects of tyramine on blood pressure and plasma catecholamines in normal and hypertensive subjects.

Responses of blood pressure and plasma catecholamines to intravenous injection of tyramine at increasing dosage (30, 45, and 60 microgram/kg, respectively) were evaluated in 25 normal subjects and 20 patients with mild essential hypertension. Basal plasma norepinephrine and epinephrine concentrations before tyramine injections were similar in the two groups. Following tyramine injection, plasma epinephrine was unchanged. Responses of plasma catecholamines and blood pressure to tyramine were similar in the two groups. Plasma norepinephrine increased significantly 2 min after a dose of 30 microgram/kg, but higher tyramine doses failed to produce a further increase in plasma norepinephrine. In contrast, pressor responses to tyramine were dose-dependent. Maximal pressor responses were observed within 23 min after injection. These findings reveal a dissociation between changes in blood pressure and plasma norepinephrine following injection of tyramine. Lack of steady state may limit the value of tyramine bolus injections as a tool for the quantitation of pressor responsiveness to variations in endogenous sympathetic output. Alternatively, it is possible that the pressor effect of tyramine may be mediated at least in part by a norepinephrine independent mechanism.

Adult↗

Responses of catecholamines and blood pressure to beta-blockade in diuretic-treated patients with essential hypertension.

Twenty patients (mean age 49 +/- 4 (SEM) yr) with mild to moderate essential hypertension were studied during placebo conditions, following 6 weeks of chlorthalidone monotherapy and 6 to 28 weeks of combined beta-blocker-chlorthalidone treatment, or vice versa. Compared to chlorthalidone therapy alone, addition of a beta-blocker to this diuretic caused a further blood pressure reduction in 11 patients (Responders); in 9 patients addition of a beta-blocking agent failed to further reduce blood pressure (Non-responders). Supine and upright plasma renin, aldosterone, norepinephrine and epinephrine levels and catecholamine excretion rates were always comparable between Responders and Non-responders. In both groups plasma and urinary norepinephrine or epinephrine values were not significantly altered following addition of a beta-blocker; heart rate and plasma renin activity were decreased in both groups to a similar extent. It is concluded that the antihypertensive mechanism of beta-blockers given to diuretic treated patients with essential hypertension is independant of renin and not associated with changes in plasma or urinary catecholamines.

Adrenergic beta-Antagonists↗

Antihypertensive mechanism of the diuretic muzolimine in mild renal failure. Roles of sodium and cardiovascular norepinephrine responsiveness.

Eighteen patients with mild impairment of renal function (glomerular filtration rate 65 +/- 5 ml/min:m +/- SEM) and hypertension (168/105 +/- 6/3 mmHg) were shown on average to have abnormally increased cardiovascular pressor responsiveness to infused norepinephrine (NE; p less than 0.05), whereas plasma and urinary NE, exchangeable body sodium and blood-volume did not differ significantly from normal. A slightly increased pressor responsiveness to angiotensin II was associated with a tendency to low plasma renin activity (PRA). Compared to placebo conditions, treatment with the loop-diuretic muzolimine in a mean dose of 35 +/- 2 mg/day for six weeks decreased blood-pressure and exchangeable sodium (p less than 0.05), and NE pressor responsiveness was restored to normal values, whilst plasma and urinary NE were not significantly changed. This was consistent with improvement of the initially abnormal relationship between NE levels and NE responsiveness factors. In contrast, the pressor dose of angiotensin II and PRA were increased to an approximatively similar extent during muzolimine treatment. These observations suggest that removal of body sodium and a decrease in NE reactivity without an equivalent increase in sympathetic nervous activity may be important complementary factors in the antihypertensive mechanisms of diuretic treatment in patients with mild renal functional impairment.

Adult↗

Acute effects of prizidilol on blood pressure, heart rate, catecholamines, renin and aldosterone in essential hypertension.

Prizidilol is a new antihypertensive agent reported to possess combined precapillary vasodilator and betareceptor-blocking properties. To clarify the profile of the acute effects of prizidilol in man, a variable dose study was performed in 8 patients with benign essential hypertension. Blood pressure, heart rate, plasma renin activity, aldosterone, plasma and urinary catecholamines and electrolytes were determined at short intervals before and up to 23 h after oral administration of placebo and prizidilol 150, 300 and 600 mg. The 4 studies were performed at weekly intervals according to a Latin square design. Prizidilol produced dose-dependent decreases in supine and upright blood pressure, with an initial change after about 2 h and maximal effects from 4 to 8 h after drug ingestion. Following a high dose of prizidilol, supine mean blood pressure (average 128 mmHg prior to treatment) was normalised (less than 107 mmHg) from 3 to 7 h and was still below predose level 23 h after ingestion. The only reported side effects were postural dizziness in 2 cases (corresponding to a fall in systolic upright blood pressure to less than 95 mmHg) and headache in one case. A biphasic variation in heart rate and plasma renin activity, with an early drop and a subsequent tendency to a slight rise, was observed after an intermediate or high dose of prizidilol. Plasma norepinephrine levels were increased by a high dose of prizidilol, while plasma epinephrine, aldosterone and plasma and urinary electrolytes were not consistently changed. Prizidilol in a a single oral dose appeared to be a potent antihypertensive agent. The profile of heart rate and plasma renin point to early dominance of beta-blockade followed by appearance of the concomitant vasodilator properties of prizidiol.

Adrenergic beta-Antagonists↗

Comparative evaluation of the new vasodilator carprazidil and minoxidil in the treatment of moderate to severe hypertension.

The efficacy and side effects of the new vasodilator carprazidil and the established vasodilator minoxidil were compared in 18 hypertensive patients inadequately controlled by 2 to 4 conventional drugs; the latter included diuretics, beta-blockers and/or sympatholytics and, in half the cases, vasodilators, such as hydralazine, diazoxide or the postsynaptic alpha-blocker prazosin. The vasodilators were withdrawn and, using a crossover design all patients received carprazidil (mean final dose 88 mg) and minoxidil (20 mg) for an average period of 5 to 6 months. The effects of the 2 agents appeared to be qualitatively and quantitatively similar. Both tended to cause sodium retention and an increase in heart rate, which required an increased dose of diuretic in one third of the cases or of a beta-blocker in a quarter. With this approach mean body weight and blood volume were not altered in the established phase of carprazidil or minoxidil treatment; heart rate and plasma norepinephrine tended to be only minimally increased, plasma renin was slightly increased, and plasma aldosterone and epinephrine were largely unchanged. Supine and upright blood pressure were reduced from initial values of 189/113 and 167/ 113 mm Hg, to 149/95 and 138/95 mm Hg (-18 and - 17%), respectively, during carprazidil, and to 154/95 and 141/96 mm Hg (-17 and - 15%) during minoxidil therapy. Hypertrichosis occurred with both agents in almost all patients, and limits their more prolonged use in females. No adverse side effects on haematological parameters, liver or renal function were observed, nor was antinuclear antibody detected. It is concluded that carprazidil and minoxidil are equivalent vasodilator agents in the treatment of severe hypertension, particularly in males.

Adult↗

Reversal or prevention of diuretic-induced alterations in serum lipoproteins with betablockers.

In 18 patients with essential hypertension serum low density lipoprotein cholesterol (LDL-C) was significantly (P less than 0.001) increased following short-term chlorthalidone therapy, but not during combination therapy with chlorthalidone and a betablocker. This tendency was similar in two subgroups which were studied with an inverse sequence of drug administration. In Group I (11 men), a 22% increase (P less than 0.01) in LDL-C during chlorthalidone monotherapy was restored to normal 6 weeks after addition to a betablocker to the diuretic; in Group II (5 men, 2 postmenopausal women) LDL-C levels were increased by 41% (P less than 0.05) 6 weeks after withdrawal of the betablocker from the combination therapy. No significant changes occurred during either the treatment phase in high density lipoprotein cholesterol or apoprotein B levels. It is concluded that combination therapy with a betablocker may prevent or reverse an increase in serum LDL-C associated with short-term chlorthalidone monotherapy.

Adolescent↗

Reversal of diuretic-induced increases in serum low-density-lipoprotein cholesterol by the betablocker pindolol.

Seventeen patients with mild to moderate essential hypertension received during three consecutive 4 wk periods a matched placebo, the thiazide-like diuretic, clopamide in a low dosage of 5 mg/day, or this diuretic combined with the betablocker, pindolol in a low dosage of 10 mg/day. Compared to placebo conditions, clopamide monotherapy significantly increased serum low-density lipoprotein cholesterol (LDL-C) by 13% (p less than 0.025). Following addition of pindolol, serum LDL-C was restored to control values. These variations in serum LDL-C were unrelated to concomitant changes in blood pressure, plasma potassium, renin activity or aldosterone levels. Blood pressure in the supine position was reduced from 152/99 +/- 13/9 mm Hg (+ SD) to 141/93 +/- 15/7 mm Hg following diuretic-monotherapy and to 139/90 +/- 12/9 mm Hg following diuretic-betablocker combination treatment. These findings suggest that antihypertensive combination treatment with low doses of clopamide and pindolol is not only effective and well tolerated, but may also avoid the increase in serum LDL-C levels occurring when the thiazide-like diuretic is given alone.

Adult↗

Enhanced cardiovascular pressor reactivity to norepinephrine in mild renal parenchymal disease.

The cardiovascular pressor responsiveness to infused norepinephrine (NE) or angiotensin II (AII) as related to endogenous plasma NE or renin levels was assessed in 20 patients with mild parenchymal kidney disease (plasma creatinine 2.20 +/- 0.58 mg/dl, +/- SEM) and in 20 normal subjects approximately matched for sex and age. The two groups did not differ significantly in mean body weight, heart rate, blood volume, plasma electrolytes, exchangeable or urinary sodium, plasma aldosterone, epinephrine and renin levels, or AII threshold or pressor doses. Basal (including pre-infusion) plasma NE levels, the relationship between plasma NE measured during NE infusion and the corresponding NE infusion rate, as well as the total plasma clearance of NE (5.0 +/- 0.8 vs. 5.5 +/- 0.5 liter/min) also did not differ significantly between the two groups. In contrast, the threshold or pressor doses of infused NE decreased significantly in the patients with kidney disease (94 +/- 11 vs. 134 +/- 14 ng/kg/min and 21 +/- 3 vs. 40 +/- 7 ng/kg/min; P less than 0.05). Moreover, based on analysis of covariance, the individual pressor doses as related to basal plasma NE levels were distributed differently (P less than 0.01) between the patients and normal subjects. These findings suggest that the kinetics of plasma NE are unaltered largely in early stage kidney disease. However, such patients tend to develop an exaggerated pressor responsiveness to NE in the presence of normal plasma NE levels. This disturbance may favor the development of hypertension.

Adult↗

Relation of arterial pressure with body sodium, body potassium and plasma potassium in essential hypertension.

1. Exchangeable sodium (NaE), plasma electrolytes and arterial pressure were measured in 121 normal subjects and 91 patients with untreated essential hypertension (diastolic greater than 100 mmHg), 21 of whom had low-renin hypertension. Plasma concentrations of renin, angiotensin II and aldosterone were measured in all hypertensive patients, total body sodium, total body potassium and exchangeable potassium (KE) in some patients. 2. Mean NaE was not different in normal and hypertensive subjects provided the two groups were matched for leanness index. In the subgroup of young hypertensive patients aged 35 years or less mean NaE was below normal. NaE was not related to arterial pressure in normal subjects but in hypertensive patients there were positive and significant correlations of arterial pressure with NaE and with total body sodium. 3. NaE and total body sodium increased with age in hypertensive but not in normal subjects. Partial regression analysis suggested that the correlation of NaE with arterial pressure was not explained by an influence of age. 4. Mean NaE was not increased and mean KE was not decreased in patients with low-renin hypertension. 5. Plasma potassium concentration, KE and total body potassium correlated inversely and significantly with blood pressure in hypertensive patients. These correlations were more marked in young than in old patients. 6. Multiple regression analysis showed that the combination of NaE and plasma potassium concentration 'explained' more of the variation of systolic blood pressure in hypertensive patients than it did in normal subjects. Plasma potassium concentration 'explained' more of the variation in young hypertensives and NaE 'explained' more in older patients. 7. Our findings suggest than changes of plasma and body potassium are important in the earlier stages of essential hypertension and that changes of body sodium become important later.

Adult↗

Studies on aldosterone responsiveness to angiotensin II during clinical variations in calcium metabolism in normal man.

1. Angiotensin II was infused at stepwise increasing dose rates (2, 4 and 10 pmol min-1 kg-1) in 12 normal subjects. Infusions were performed in the presence of normocalcaemia, mild hypercalcemia induced by concomitant calcium gluconate infusion, and after 2 weeks of treatment with nifedipine. 2. Pre-infusion plasma levels of angiotensin II, renin or aldosterone were not altered by acute mild hypercalcaemia or administration of nifedipine. The angiotensin II-induced increases in plasma aldosterone were also similar under the three study conditions. 3. Variations in calcium metabolism occurring under clinical conditions appear to play a minor role in modulating the angiotensin II-dependent pathway of aldosterone regulation in normal man.

Adult↗

Lasting improvement of renovascular hypertension by transluminal dilatation of atherosclerotic and nonatherosclerotic renal artery stenoses. A follow-up study.

Sixteen consecutive patients with renovascular hypertension were treated by transluminal dilatation and observed during 6 - 39 months (mean 21.8 months). Poststenotic renal artery pressure increased (p less than 0.001) and the renal arteries were patent on angiograms taken immediately after dilatation. In 13 patients, angiography was repeated 2 - 9 months later; at that time the selective renal vein renin ratio had decreased (p less than 0.001). At the end of the follow-up, blood pressure was improved or normal in 14 cases. One of the eight patients with atherosclerosis was normotensive without treatment, compared with five of six patients with fibromuscular dysplasia (p less than 0.05). The results in two cases with vasculitis are uncertain. The four patients with relapses, one after intimal catheter dissection, were treated successfully by redilatation. Thus, renovascular hypertension can be improved by transluminal dilatation in patients with atherosclerosis and in patients with fibromuscular dysplasia with lasting success and a low morbidity rate.

Adult↗