PubMed Health⌕ Search

Biomedical subjects

W J Leahey

Publications and source records attributed to W J Leahey.

16 recordsLinked to original sources
PubMed1988

Short-term effects of alcohol on peripheral blood flow, platelet aggregation and noradrenaline output in normal man.

The effects of acute oral administration of alcohol on finger and forearm blood flow, platelet aggregation and plasma noradrenaline were examined over a three-hour period in a group of healthy male volunteers. Finger blood flow was increased at 15, 30 and 60 min and skin temperature was raised at 30 and 60 min. Digital systolic blood pressure was decreased at 15 and 30 min. No change in forearm blood flow was observed. A linear correlation was observed between finger blood flow, skin temperature and plasma alcohol concentrations. No significant changes were observed in platelet aggregation nor in plasma noradrenaline levels. Alcohol appears to have a greater effect on digital and skin blood flow as compared with muscle blood flow.

Administration, Oral↗
PubMed1987

The effect of chronic captopril therapy on adrenergic receptors, plasma noradrenaline and the vascular responses to infused noradrenaline.

Adrenergic receptors (alpha 2, beta 2), plasma noradrenaline, heart rate and the pressor responsiveness to infused noradrenaline were examined in ten healthy male volunteers before and after 2 weeks of placebo or captopril therapy in a double blind cross-over study. No significant differences in these measurements were observed between the captopril and placebo treated groups. The study shows that in sodium replete normotensive subjects, long-term angiotensin converting enzyme inhibition does not lead to changes in adrenoceptor density. There is also no alteration in plasma noradrenaline levels nor in the pressor responsiveness to infused noradrenaline. These data suggest that the known interaction between the renin-angiotensin system and the sympathetic nervous system observed in animals is probably of little significance in man.

Adult↗
PubMed1987

Recombinant human interferon alpha increases oestrogen receptor expression in human breast cancer cells (ZR-75-1) and sensitizes them to the anti-proliferative effects of tamoxifen.

Exposure of ZR-75-1 human breast cancer cells for 48 h to human recombinant interferon alpha (IFN alpha) resulted in increased expression of oestrogen receptors as measured in a whole cell binding assay. This effect was inversely proportional to dose being significant following treatment with 10-100 IU IFN ml-1 and was only observed at a low initial cell plating density. The extent of the increase in oestrogen receptor levels ranged from 1.2- to 7.2-fold following treatment with 10 IU IFN ml-1. No increase in progesterone receptor expression was observed under the same experimental conditions. Concentrations of IFN which increased oestrogen receptor levels had no effect on cell proliferation. IFN (500 IU ml-1) inhibited cell proliferation and the combination of this treatment with tamoxifen (2 microM) had a greater anti-proliferative effect than either drug alone although there was no evidence of synergism. However, a 5-day pretreatment of cells with IFN (10 IU ml-1) markedly sensitised them to the growth-inhibiting effect of a subsequent 6-day exposure to tamoxifen.

Binding, Competitive↗
PubMed1985

The effects of propranolol and digoxin on the acute vascular responses to frusemide in normal man.

To examine the importance of acute frusemide-induced renin release in the production of the acute peripheral venous and arterial responses to frusemide in man, the effects of two drugs, previously described as inhibitors of acute frusemide-induced renin release, propranolol and digoxin, were examined. Propranolol abolished the acute increases in venous capacitance and blood pressure and attenuated the increases in forearm vascular resistance produced by frusemide. The acute increases in plasma renin activity and plasma aldosterone concentrations were also abolished. Pre-treatment with digoxin had no effect on the acute peripheral vascular responses to frusemide and failed to inhibit the acute increases in plasma renin activity and plasma aldosterone produced by frusemide. The study provides further evidence of a relationship between acute frusemide-induced renin release and the acute peripheral vascular effects of frusemide in man.

Adolescent↗
PubMed1984

Differential blockade of alpha-adrenoceptors by indoramin.

The effect of equihypotensive single oral doses of indoramin (mean dose 67 mg), phenoxybenzamine (mean dose 50 mg), hydralazine (mean dose 133 mg) and placebo on arterial pressure and heart rate in the supine and standing position was studied in six normal volunteers. Observations were made before and at 2 and 4 h after drug administration. Plasma noradrenaline (NA) was measured at each time interval in the supine position, and after 4 min of standing. Plasma renin activity (PRA) was measured at each time interval after 30 min in the standing position. The three active drugs reduced systolic arterial pressure in the standing position to a similar extent (indoramin, -24 mm Hg; phenoxybenzamine, -23.4 mm Hg; hydralazine, -30.4 mm Hg). The maximum effect of indoramin and phenoxybenzamine was observed at 4 h, and of hydralazine at 2 h after drug administration. The reductions of arterial pressure in the standing position were accompanied by increases in heart rate, plasma NA and PRA. Small increases were observed after indoramin (heart rate, + 9.2 beats min-1; plasma NA, + 126 pg/ml; PRA, + 0.33 ng angiotensin 1 ml-1 h-1), greater increases after phenoxybenzamine (heart rate, + 20; plasma NA, + 210; PRA, + 0.47), and the greatest increases after hydralazine (heart rate, + 26; plasma NA, + 250; PRA, + 1.16). In the supine position, indoramin and phenoxybenzamine produced no effect on arterial pressure, heart rate or plasma NA. Hydralazine produced small reductions in diastolic pressure, which were accompanied by an increase in heart rate of 25.5 beats min-1 (P less than 0.01 when compared to placebo) and in plasma NA of 223 pg ml-1 (P less than 0.05). Plasma NA, PRA and heart rate increased together and may be regarded as three interdependent indices of sympathetic activity. Indoramin reduced the degree of increase of plasma NA, PRA and heart rate per unit fall in pressure, when compared to phenoxybenzamine and hydralazine. The effect of phenoxybenzamine and hydralazine on the degree of increase was similar. The results are consistent with the hypothesis that indoramin produces selective postsynaptic alpha 1-adrenoceptor blockade in man, and therefore produces relatively less tachycardia and NA increase than does a non-selective alpha-adrenoceptor antagonist (phenoxybenzamine) or an arteriolar vasodilator (hydralazine).

Adolescent↗
PubMed1984

Effect of indoramin, labetalol and alinidine on sympathetic function in normal man.

The effects of single oral doses of indoramin (mean dose 58 mg), abetalol (mean dose 150 mg), alinidine 80 mg and placebo on arterial pressure and heart rate in the supine and standing positions were studied in six normal volunteers. Doses were chosen to give equivalent reductions of arterial pressure in the standing position. Observations were made before and at 2 and 4 h after drug administration. Plasma noradrenaline (NA) was measured at each time interval in the supine position, and after 4 min of standing. Plasma renin activity (PRA) was measured at each time interval after 30 min in the standing position. In the supine position, alinidine produced a significant reduction of systolic arterial pressure from 124.0 +/- 3.0 mm Hg to 104.3 +/- 4.1 mm Hg at 2 h (P less than 0.01) and to 101.7 +/- 2.2 mm Hg at 4 h (P less than 0.01). Diastolic pressure was reduced from 74.7 +/- 2.6 mm Hg to 57.0 +/- 4.6 mm Hg at 4 h (P less than 0.01). Arterial pressure was unchanged after indoramin or labetalol administration. In the supine position, heart rate was unchanged after indoramin, and small reductions were observed after labetalol and alinidine. Indoramin produced a significant increase in plasma NA. A small increase of plasma NA was observed after labetalol, and a small decrease after alinidine. In the standing position, the three active drugs reduced systolic arterial pressure to a similar extent (indoramin, -26.7 mm Hg at 4 h after drug administration; labetalol, -21.3 mm Hg at 2 h; alinidine, -21.7 mm Hg at 4 h).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

The dose-response characteristics of the acute non-diuretic peripheral vascular effects of frusemide in normal subjects.

The peripheral venous and arterial effects of frusemide, plasma renin activity and plasma frusemide concentrations were examined during the 15 min period following the i.v. administration of 0, 5, 10, 20, 40 and 80 mg of frusemide in a group of nine salt depleted volunteers. The responses to 80 mg frusemide given orally during the 1 1 h period after administration were also examined. Increases in venous capacitance 5 min after administration of 5 and 10 mg frusemide were observed (P less than 0.05) but no significant increases were apparent after the higher doses. At 10 min, the increases in venous capacitance showed a flat dose response effect with significant increases throughout the dose range (5-80 mg). Decreases in forearm blood flow occurred at 5 and 10 min after frusemide administration at all the doses studied (P less than 0.05) while blood pressure responses at 10 min showed increasing effect with increasing dose. An oral dose of 80 mg frusemide produced a rise in venous capacitance 15 min after administration and a decrease in forearm blood flow during the period 15-60 min without any alteration in heart rate or blood pressure.

Adolescent↗
PubMed1983

The effects of captopril on the acute vascular responses to frusemide in man.

To examine the importance of angiotensin II formation in the production of frusemide's acute peripheral venous and arterial responses, the effect of pretreatment with captopril was studied. Captopril abolished the acute increases in venous capacitance and blood pressure and attenuated the increases in forearm vascular resistance produced by intravenous frusemide. The study provides evidence that angiotensin II formation performs an essential role in the production of the acute vascular effects of frusemide in man.

Adolescent↗
PubMed1981

Observation on the efficacy and pharmacokinetics of betaxolol (SL 75212), a cardioselective beta-adrenoceptor blocking drug.

1 Observations were made in five subjects who exercised before and at 2, 3, 6, 8, 24, 33 and 48 h after the oral administration of placebo and 5, 10, 20 and 40 mg betaxolol. 2 The exercise heart rate remained constant at all times after the placebo. All doses of betaxolol significantly reduced the exercise tachycardia at all times. The maximum effect (34.4 +/- 2.2%) occurred after 40 mg. 3 There was a small decline in effect from the peak to 24 h when 40 mg produced a 23.3 +/- 2.7% reduction and a further decline to 48 h when there was a 14.6 +/- 1.8% reduction. 4 Plasma levels of betaxolol were measured in these studies. The peak plasma concentration occurred between 3 and 8 h with different doses. The plasma elimination half-lives after 10, 20 and 40 mg were 11.4 +/- 2.5, 15.9 +/- 4.9 and 15.1 +/- 3.1 h. 5 The effects of 40 mg betaxolol, 200 mg atenolol, 160 mg propranolol, 160 mg oxprenolol, 400 mg sotalol and placebo on an exercise tachycardia were compared in five subjects who received all treatments in random order. 6 There was no significant difference in the maximum reduction produced in an exercise tachycardia by the different drugs. 7 The effect of all drugs decreased with time. The effect of oxprenolol had worn off at 24 h but at 48 h only atenolol and betaxolol produced significant reductions in the exercise tachycardia. 8 Plasma concentrations of the different drugs were measured and plasma elimination half-lives determined. The half-life for betaxolol was 24.5 h which was longer than that for any of the other drugs. 9 These observations show that betaxolol is a potent beta-adrenoceptor antagonist with a long duration of effect on an exercise tachycardia and a long plasma elimination half-life.

Adrenergic beta-Antagonists↗
PubMed1979

Observations on some properties of a long-acting preparation of propranolol.

1. The effects of 160 mg of propranolol and 160 mg of a long-acting (LA) formulation of propranolol were studied in healthy subjects. 2. Both drugs reduced an exercise tachycardia but the peak was less and the 24 h effect greater after long-acting propranolol than after propranolol. 3. These differences were maintained on repeated dosing for 8 days. 4. In contrast to single doses of 400 mg of sotalol, 160 mg of oxprenolol and 160 mg of slow-release oxprenolol, the peak effect of long-acting propranolol was less and that at 24 h was greater.

Adult↗
PubMedDate not supplied

Pharmacokinetics of praziquantel in healthy volunteers and patients with schistosomiasis.

The pharmacokinetics of a novel praziquantel preparation (Distocide) were investigated in Sudanese patients with hepatosplenic schistosomiasis and in healthy volunteers, and compared with those of Biltricide. The results of the first study indicated greater (P less than 0.05) plasma concentrations of Biltricide at 1.5, 2, 3 and 5 h after administration than with Distocide; plasma elimination half-lives (t 1/2) were not significantly different. In patients with hepatosplenic schistosomiasis, higher plasma levels of Distocide were noted (P less than 0.05 at 8 h) compared to healthy controls; however, due to wide inter-individual variations, there were no significant differences in maximum plasma concentration, time to maximum plasma concentration, area under the plasma concentration curve (AUC), volume of distribution, or clearance; t 1/2 was greater (P less than 0.05) in patients (11.9 +/- 5.4 h) than controls (2.3 +/- 0.4 h). In the presence of food, higher plasma concentrations of Distocide occurred compared to the fasting state; AUCs were greater (P less than 0.01) in both food groups, although the values of t 1/2 were shorter. The lower plasma levels and longer duration of action of Distocide may be advantageous in reducing side effects and prolonging exposure of the schistosomes to the drug.

Adult↗