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Biomedical subjects

W H Ziegler

Publications and source records attributed to W H Ziegler.

At least 73 records · Page 4Linked to original sources

Increased ratio between changes in blood pressure and plasma norepinephrine in essential hypertension.

The pathogenic role of the sympathetic system in essential hypertension was evaluated by combined analysis of plasma catecholamine levels and the pressor sensitivity to endogenous norepinephrine. The latter was estimated indirectly by the ratio between changes in blood pressure and those in plasma norepinephrine after adrenergic neuronal blockage with debrisoquine (given orally for 6 weeks). Normal subjects and patients with borderline or established essential hypertension had comparable pretreatment levels of plasma norepinephrine and epinephrine. Debrisoquine lowered plasma norepinephrine by a similar degree (almost 50%) in these three groups; in contrast, blood pressure decreased only slightly in normal or borderline hypertensive subjects [-3.4 +/- 3.2% and -5.4 +/- 1.6% (SE), respectively] but fell significantly more (P less than 0.005) in patients with established essential hypertension (-20.7 +/- 3.9%). The ratio between percentile changes in blood pressure and those in endogenous norepinephrine levels was comparable in normal and borderline hypertensive subjects (0.03 +/- 0.08 and 0.17 +/- 0.04, respectively), but increased (P less than 0.001) in established essential hypertension (0.62 +/- 0.11). This suggests that essential hypertension may be maintained, at least partly, by the inappropriate association of normal plasma norepinephrine levels with increased norepinephrine pressor sensitivity.

Blood Pressure↗

Single-dose pharmacokinetics of the trypanosomicide benznidazole in man.

The single-dose pharmacokinetics of N-benzyl-2-nitro-1-imidazole acetamide (benznidazole, Radanil) following administration of 1 tablet Radanil (100 mg) was investigated in six healthy volunteers. The absorption of the drug was fairly rapid. Peak plasma levels of 2.2--2.8 microgram/ml were reached after 3--4 h. The log c versus time curves showed little interindividual variation. The shape of the curves indicates that the drug follows the kinetics of a one-compartment model. The elimination half-lives ranged from 10.5 to 13.6 h, with a mean value of 12 h. The relative bioavailability of the compound (oral tablet versus oral solution) was checked in three of the subjects and found to be 91.7% on an average.

Biological Availability↗

[Significance of noradrenaline in the pathogenesis of essential hypertension. Preliminary report].

The pathogenic role of the sympathetic system in essential hypertension was evaluated by combined analysis of urinary and plasma catecholamine levels and pressor sensitivity to endogenous noradrenaline. The latter was estimated indirectly by the ratio between percentile changes in blood pressure and plasma noradrenaline following adrenergic neuronal blockade with the agent debrisoquine. In normal and mildly hypertensive (141/91 to 160/105 mm Hg) subjects, supine or upright plasma levels and excretion rates of noradrenaline correlated (p less than 0.01) with age and were comparable; no correlation was present in patients with moderate to severe hypertension (greater than 160/105 mm Hg) who tended to have supernormal noradrenaline levels under the age of 40 years. Adrenaline values were normal in essential hypertension. Pressor sensitivity to noradrenaline was comparable in normal and mildly hypertensive subjects (0.03 +/- 0.08 [SE] and 0.17 +/- 0.04, respectively) but increased (p less than 0.001) in moderate to severe hypertension (0.62 +/- 0.11). These findings suggest that moderate to severe essential hypertension may be maintained, at least partly, by the inappropriate association of normal plasma noradrenaline levels with increased noradrenaline pressor sensitivity. This may also provide a rational basis for the use of pharmacologic adrenergic inhibition in the treatment of moderate to severe essential hypertension.

Adolescent↗

[Venographic and laboratory investigation of pheochromocytoma (author's transl].

Twenty-eight patients with the clinical diagnosis of pheochromocytoma were studied by adrenal venography and catecholamine determination in selective venous blood sampling. Results of this technique are correlated to pathologic findings. 87% of the existing pheochromocytomas were correctly identified. In cases with corresponding venographic and laboratory results correct preoperative tumor localization was established in 97%. False interpretations are discussed in relation to the phlebographic findings and the assay of the catecholamines.

Adolescent↗

Interrelations between age and plasma renin, aldosterone and cortisol, urinary catecholamines, and the body sodium/volume state in normal man.

Interrelations between age and plasma renin, aldosterone and cortisol levels, urinary catecholamiens, plasma and blood volumes, exchangeable body sodium and blood pressure wwere studied in 28 young (19 to 29 years), 16 middle-aged (32 to 58 years) and 15 elderly (60 to 74 years) healthy subjects. Supine and upright plasma renin and supine aldosterone levels decreased while urinary noradrenaline excretion rate increased progressively with aging (r= greater than 0.34; p less than 0.05), with significant differences in mean values between young and elderly subjects (p less than 0.02). There was also an age-related decrease in upright plasma aldosterone concentration, although this was no statistically significant. Furthermore, mean plasma cortisol concentrations increased in response to upright posture in elderly ( + 50%; p less than 0.02), but not in young ( --10%) or middle-aged ( --8%) subjects. Blood pressure correlated with age ( r =0.35; p less than 0.05) or noradrenaline excretion rate ( r= 0.34) in the entire study population and with blood volume in the elderly ( r = 0.68), but not in the young or middle-aged study. Groups. There were no significant age-related differences in the body sodium/volume state, basal plasma cortisol levels or urinary adrenaline excretion rate, and plasma renin or aldosterone levels did not correlate with these parameters or with blood pressure. It is concluded that the influence of age on plasma renin or aldosterone levels, plasma cortisol responsiveness to upright posture, and urinary noradrenaline excretion should be taken into consideration, whenever these factors have to be interpreted in patients with arterial hypertension or other clinical disorders. Further more, these data are conssitent with the possiblity that in normal man increases in supine blood pressure with aging may be related at least partly to concomitant changes in free peripheral noradrenaline.

Adult↗

Interrelations among blood pressure, blood volume, plasma renin activity and urinary catecholamines in benign essential hypertension.

Interrelations among blood pressure, circulatory volume, plasma renin activity (PRA) and urinary catecholamine excretion rates were studied in normal subjects and in patients with benign essential hypertension. Mean plasma or blood volumes related to lean body mass, products of blood volume and the logarithm of PRA, and catecholamine excretion rates did not differ significantly between normal and hypertensive subjects. In both normal subjects and hypertensive patients, blood pressure levels correlated positively with the noradrenaline excretion rate (r = 0.40 and 0.36, respectively; p less than 0.025) but not with adrenaline excretion, circulatory volume or the volume-renin product. The logarithm of PRA correlated inversely with mean blood pressure in normal subjects (r = 0.40; p less than 0.001) but not in hypertensive patients; however, there was no convincing evidence for an inappropriate blood pressure-PRA relationship as a prominent feature in the hypertensive patients. PRA did not correlate with blood volume. Patients with low PRA relative to sodium excretion (21 per cent of hypertensive population) were consistently normovolemic, but they tended to be older and excreted less (p less than 0.025) adrenaline than patients with normal or high PRA. The patient subgroup with high PRA relative to sodium excretion (11 per cent of population) was hypovolemic (p less than 0.02); despite this, urinary sodium output was high (172 +/- 64 meq/24 hours). These data reveal no evidence for major roles of PRA, circulatory volume and free peripheral catecholamines in the maintenance of benign essential hypertension. Essential hypertension with low PRA is usually not a hypervolemic state, but it may reflect diminished adrenergic activity, factors associated with aging and effects of a high systemic pressure. High PRA in benign essential hypertension may be at least partly a consequence of hypovolemia resulting from high blood pressure-induced sodium diuresis.

Adult↗

Sodium, renin, aldosterone, catecholamines, and blood pressure in diabetes mellitus.

Interrelations among plasma renin activity (PRA), aldosterone and cortisole levels, 0lood volume, exchangeable sodium, urinary catecholamines, and blood pressure were studied in 35 normal subjects and 60 age-matched non-azotemic patients with diabetes mellitus (60% with hypertension, 15% with orthostatic hypotension). Basal PRA, plasma aldosterone, cortisol, blood volume, plasma potassium, and urinary electrolytes were comparable in diabetic and normal subjects. Diabetic patients, however, had a 10% increase in body sodium (P less than 0.01), and 8% of them showed normal postural PRA responses and subnormal aldosterone responses; 22% had subnormal PRA and normal aldosterone responses, and 17% had subnormal responses of PRA and aldosterone. Non-PRA-related aldosterone responses could not be explained by ACTH or electrolytes. Orthostatic decreases in blood pressure correlated (P less than 0.01) with both catecholamine excretion and basal PRA. This suggests that in diabetes mellitus, body sodium is increased. Basal PRA and plasma aldosterone are usually normal, but their postural responses are frequently impaired. Absent aldosterone responses, despite normal PRA responsiveness, may reflect an adrenal abnormality or an ineffective form of renin. Marked postural aldosterone stimulation, unrelated to PRA, ACTH, or electrolytes, points to a potent unknown factor in aldosterone control. Low levels of free peripheral catecholamines and PRA may be complementary factors contributing to postural hypotension.

Adult↗

Bioavailability from various galenic formulations of flunitrazepam.

The absolute and relative bioavailability of flunitrazepam (Rohypnol) tablet, oral solution and suppository formulations was determined in a cross-over study on 6 healthy volunteers. The tablet and the oral solution were shown to be bioequivalent, absorption being at least 80%. For flunitrazepam suppositories the bioavailability was found to be about 50%. The plasma concentrations are described on the basis of a three-compartment model, the adjustment of the curves from the same subject being made simultaneously. The central compartment and the second compartment are about equal in size and rapid exchange takes place between them. The third compartment is about four times as large as the central one. The slow reflux of the compound from the third to the first compartment is the rate determining factor for the overall elimination in the beta-phase.

Adult↗

[Correlations between blood pressure, blood volume, plasma renin and urinary catecholamines in normal subjects and in patients with benign essential hypertension].

Interrelations between blood pressure, circulatory volume, plasma renin activity (PRA) and urinary catecholamine excretion rates were studied in normal subjects and patients with benign essential hypertension. Mean plasma or blood volumes related to lean body mass, products of blood volume and the logarithm of PRA, and catecholamine excretion rates did not differ significantly as between normal and hypertensive subjects. In both normal subjects and hypertensive patients, blood pressure correlated positively with noradrenaline excretion rate (r = 0.40 and 0.36 respectively; p less than 0.025), but not with adrenaline excretion, circulatory volume or the volume-renin product. The logarithm of PRA correlated inversely with mean blood pressure in normal subjects (r = -0.40; p less than 0.001), but not in hypertensive patients; however, there was no convincing evidence of an inappropriate blood pressure-PRA relationship as a prominent feature in the hypertensive patients. PRA did not correlate with blood volume. Patients with low PRA relative to sodium excretion (21% of hypertensive population) were consistently normovolemic, but tended to be older and excreted less (p less than 0.025) adrenaline than normal or high-PRA patients. The patient subgroup with high PRA relative to sodium excretion (11% of population) was hypovolemic (p less than 0.02); despite this, urinary sodium output was high (172 +/- 64 meq/24 hr). These data reveal no evidence for major roles of PRA, circulatory volume and free peripheral catecholamines in the maintenance of benign essential hypertension. Low-PRA essential hypertension is usually not a hypervolemic state, but may reflect diminished adrenergic activity, factors associated with aging and effects of a high systemic pressure. High PRA in benign essential hypertension may be at least partly a consequence of hypovolemia resulting from high blood pressure-induced sodium diuresis.

Blood Pressure↗

[Endocrinological studies in arterial hypertension. Search for phaeochromocytoma].

Elevated urinary catecholamines and their metabolites are the only findings which confirm the presence of pheochromocytoma. This examination is of particular interest if carried out in urine produced after spontaneous hypertensive episodes. Pharmacologic tests when carried out under standard conditions have proven to be a reliable aid in cases of suspected pheochromocytoma. Roentgenographic studies, determination of local plasma catecholamine concentrations and blood volume control should be undertaken in these patients before surgical procedure.

Angiography↗