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Biomedical subjects

B R Walker

Publications and source records attributed to B R Walker.

215 records · Page 12Linked to original sources
PubMed1977

A multicentre study comparing mazindol and placebo in obese patients.

Mazindol is chemically unrelated to the phenethylamines and has not shown the side-effects or abuse potential of the amphetamine anorectics. To further define its potential for causing weight loss, a six-week double-blind placebo controlled study was undertaken in four centres. A common protocol was used except in one centre, behavioural modification also was employed, whereas in the other centres, no additional measures were used to cause weight loss. Two hundred and forty-five obese patients were assigned randomly to two mazindol groups and one placebo group in each centre. Ninety-eight and forty patients receiving mazindol and placebo respectively completed the protocol. The conclusions were: (a) no significant clinical or laboratory abnormalities occurred from mazindol therapy, (b) the placebo therapy patients did not lose weight without behavioural modification, (c) the placebo therapy group had a higher drop-out rate compared to the mazindol therapy group attributable to the patients' dissatisfaction with failure to lose weight, (d) mazindol therapy without behavioural modification and behavioural modification alone both resulted in a statistically significant mean weight loss of 1 pound/patient/week and (e) mazindol plus behavioural modification resulted in a greater mean weight loss of 1/2 pound/patient/week than with behavioural modification alone. Hence, mazindol is of value in the initial therapy of obesity.

Adolescent↗
PubMed1976

Guanabenz effects on blood pressure and noninvasive parameters of cardiac performance in patients with hypertension.

Guanabenz (2,6 dichlorobenzylidene amino guanidine acetate) is a new antihypertensive whose mechanism of action appears to involve both central alpha adrenergic stimulation leading to suppression of sympathetic nervous system activity from bulbar vasoconstriction centers as well as peripheral adrenergic neuron blockade. In this study, the drug was shown to produce a statistically and clinically significant decrease in blood pressure during a 4-wk placebo-controlled double-blind study. For three additional months continued efficacy and safety were shown under open conditions in 17 hypertensive patients. Mild sedation occurred, but there were no postural hypotension, tachycardia, evidence of sodium retention, gastrointestinal disturbances, or electrocardiographic (ECB) abnormalities. Noninvasive parameters of cardiac performance in 10 patients after single doses of guanabenz showed no significant changes. Although the numbers of patients were relatively small, the data suggest that this new drug may be a useful antihypertensive agent that warrants further investigation.

Adult↗
PubMed1970

Effects of increased sodium delivery on distal tubular sodium reabsorption with and without volume expansion in man.

The separate effects of volume expansion and of increased delivery of sodium on sodium reabsorption in the diluting segment of the distal nephron were studied in man. In six normal subjects during a sustained water diuresis, sodium delivery to the distal nephron was increased without volume expansion by the administration of acetazolamide. In these subjects, free water clearance rose linearly as a function of urine flow. In five patients with complete, central diabetes insipidus, distal sodium delivery was increased by the infusion of hypertonic saline during a sustained water diuresis. In four of these five patients, changes in free water clearance were also observed during hypertonic saline diuresis in the presence of distal blockade of sodium reabsorption with chlorothiazide. At high rates of distal delivery the following observations were made: (a) free water clearance was lower and fractional sodium excretion higher during saline diuresis compared to acetazolamide diuresis; (b) although free water clearance was moderately reduced by chlorothiazide at low rates of urine flow, there was no difference in free water clearance between saline loading alone and saline plus chlorothiazide at high rates of urine flow; and (c) during saline loading free water clearance rose without evidence of a limit when increased distal delivery was accompanied by spontaneous increases in glomerular filtration rate, but tended toward a limit when glomerular filtration rate remained constant. The data indicate that during acute volume expansion with saline, there is a decrease in the fraction of delivered sodium reabsorbed in the distal nephron when compared to the response of the distal nephron to comparable increases in distal sodium delivery in the absence of volume expansion.

Acetazolamide↗
PubMedDate not supplied

Effects of food on oxaprozin bioavailability.

Twelve healthy volunteers received single 1200-mg oral doses of oxaprozin while fasting and immediately after a standard breakfast in a two-period crossover design with three weeks between administrations. Oxaprozin plasma concentrations were monitored during a 10-day period after each dose. No statistically significant differences were noted between kinetic parameters obtained in the fasting and post-prandial states for mean peak plasma concentrations (Cmax, 103 vs. 109 micrograms/ml), absorption rate constants (ka, 1.1 vs. 0.8 h-1), or total AUC (7042 vs. 7066 micrograms/ml X hr). Compared with doses administered during fasting, postprandial doses led to a delay in the onset of absorption in the gastrointestinal tract (lag time t0, 24 vs. 9 min), but not in the peak time (tmax approximately 5 hours). Oxaprozin's mean residence time t was slightly shorter for subjects in the postprandial state (72 hours) than for those in fasting state (73 hours), probably because of the intrasubject variability in half-life (48 vs. 50 hours). The results of this study indicate that the ingestion of food has no effect on the bioavailability of oxaprozin.

Adult↗
PubMedDate not supplied

Cadmium nephropathy: monitoring for early evidence of renal dysfunction.

Prospective studies in humans comparing various tests of cadmium-induced nephropathy have not been reported. Consequently, it is not possible to ascertain which screening methods should be followed in order to detect early nephropathy at a reversible stage. To obtain such data, the authors studied 23 cadmium workers with periodic analyses of blood/urine cadmium levels, hair cadmium content, urinary cytologies, creatinine clearance and urinary levels of lysozyme, beta-2-microglobulins, immunoglobulins, and aminoacids. Blood/urine levels were useful only as indices of acute environmental exposure and not as predictors of total body content or possible nephropathy. Hair content was elevated in most workers. Urine cytology was not reliable. Until further data are available, it is suggested that all five measures of renal function be used in screening and follow-up of cadmium workers for preventing nephropathy.

Adult↗
PubMedDate not supplied

Renal and cardiovascular responses to acute hypercapnic acidosis in conscious dogs: role of renin--angiotensin.

Patients with pulmonary dysfunction and CO2 retention have renal hemodynamic abnormalities accompanied by increased plasma renin activity. To determine if hypercapnia impairs renal function, particularly through the renin-angiotensin system, the effects of acute hypercapnic acidosis (HC), using 8.5% CO2, were measured in five unanesthetized dogs during (a) the intact state; (b) renin-angiotensin antagonism using either 1-sarcosine, 8-glycine angiotensin II ( [Sar1, Gly8] AII) or SQ 14,225; and (c) exogenous angiotensin II infusion. As partial arterial carbon dioxide pressure (PaCO2) increased (p less than 0.05) from control (C) of 35 +/- 1 (SEM) to 48 +/- 1 mm Hg during HC, arterial pH fell (p less than 0.05) from 7.36 +/- 0.01 to 7.24 +/- 0.005. Renal function was uncompromised with HC, and glomerular filtration rate (GFR) and urinary sodium excretion increased (p less than 0.05) despite a fourfold rise in plasma renin activity from C of 0.6 +/- 0.3 to 2.2 +/- 0.8 ng AI ml-1 h-1 during HC. Administration of [Sar1, Gly8] AII during HC did not consistently alter systemic or renal hemodynamic responses, and effects of SQ 14,225 during HC were also observed during normocapnia. Although systemic vascular responses to exogenous AII infusion were similar, the renal vasoconstrictor response was antagonized during HC with unchanged GFR and renal blood flow. These findings indicate that despite activation of the renin-angiotensin system, acute hypercapnic acidosis is unassociated with impairment of renal function in unanesthetized dogs. This may be related to diminished renal vascular AII responsiveness during hypercapnia.

Acidosis↗
PubMedDate not supplied

Cardiovascular and renal effects of the beta-blocker SE2395 in conscious normotensive dogs.

The cardiac and renal hemodynamic effects of SE2395, a beta-blocking agent, were examined after intravenous administration (50 micrograms/kg) in normotensive conscious dogs. Beta-blocking action of SE2395 was evidenced by a reduction in heart rate and cardiac output without change in the mean arterial pressure. An increase in glomerular filtration rate (inulin clearance) and a slight enhancement in effective renal plasma flow (para-aminohippurate clearance) were observed without attendant decreases in plasma renin activity. An increase in urinary sodium excretion was also observed; urinary prostaglandin E2 excretion was, however, unchanged. We conclude that at effective beta-blocking dosage SE2395 does not induce any detrimental effect on renal function in conscious dogs.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Involvement of L-type calcium channels in hypoxic relaxation of vascular smooth muscle.

In the systemic vasculature, hypoxia elicits a local vasodilator response that may be partially mediated by ionic channels on vascular smooth muscle, such as adenosine triphosphate sensitive K+ channels. Recent electrophysiological studies suggest that hypoxia may also inhibit voltage-dependent Ca2+ channels (L type) on peripheral vascular smooth muscle cells. We hypothesized that hypoxia elicits relaxation of vascular smooth muscle by inhibiting L-type Ca2+ channels. In endothelium-denuded rat thoracic aortic rings contracted with phenylephrine, mild and moderate hypoxia (PO2 35 and 20 mm Hg, respectively) elicited significant relaxation. Pretreatment with the L-type Ca2+ channel antagonist nifedipine completely inhibited mild hypoxic relaxation and diminished relaxation under moderate hypoxia, whereas glibenclamide, a blocker of adenosine triphosphate sensitive potassium channels, only attenuated the response to moderate hypoxia. In rings contracted with the L-type Ca2+ channel agonist (-)BAY K 8644 both mild and moderate hypoxia elicited almost complete relaxation. Furthermore, in rings contracted with hyperkalemic solutions (85 mM K+ or 120 mM K), mild and moderate hypoxia elicited significant relaxations. Thus, we conclude that hypoxia acts directly on vascular smooth muscle to cause relaxation in part by inhibiting L-type Ca2+ channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMedDate not supplied

Clinical investigation of 11 beta-hydroxysteroid dehydrogenase.

At least two isoforms of 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) have been identified, and clinical studies have illustrated their physiological and pathological significance. In the kidney, a high affinity 11 beta-OHSD2 inactivates cortisol to cortisone and protects mineralocorticoid receptors from cortisol. In the liver, a low affinity 11 beta-OHSD1 converts cortisone to cortisol, and may ensure that glucocorticoid receptors are adequately exposed to cortisol. In vascular smooth muscle, the conversion of cortisol to cortisone influences vascular tone. Defects in 11 beta-OHSD2 probably account for mineralocorticoid excess in the syndromes of Apparent Mineralocorticoid Excess, licorice administration, and ectopic ACTH syndrome. Defects in 11 beta-OHSD1 may be important in essential hypertension, and polycystic ovarian syndrome. The underlying mechanism for all of these defects, and the putative role of endogenous inhibitors of 11 beta-OHSD, remains unclear. In future, the measurement of the activity of individual isoforms should resolve this uncertainty.

11-beta-Hydroxysteroid Dehydrogenases↗