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Biomedical subjects

A McLean

Publications and source records attributed to A McLean.

At least 145 records · Page 8Linked to original sources
PubMed1981

Low oral bioavailability of dihydroergotamine and first-pass extraction in patients with orthostatic hypotension.

The relative importance of the effect of absorption and first-pass extraction in bioavailability and clinical effectiveness of oraldihydroergotamine (DHE) was examined in six subjects with orthostatic hypotension. Maximum increases in systolic blood pressure of standing subjects occurred within 15 min of intravenous administration (10 micrograms/kg); after 30 min pressure declined linearly with respect to time over the ensuing 3 hr. Plasma DHE concentrations declined biexponentially with respect to time. Mean plasma half-life was 2.15 hr and plasma clearance averaged 862 ml/min. There was no rise in "standing" systolic blood pressure on oral administration (200 to 600 micrograms/kg). Peak plasma concentrations ranged from less than 0.1 to 2 ng/ml. Apparent oral absorption for DHE ranged from 19.5% to 53.3% while systemic bioavailability varied from less than 0.1% to 1.5%. when glyceryl trinitrate was taken orally with DHE, the bioavailability of the latter increased between 56% and 370% over the 0.1% to 1.5% without any apparent alteration in DHE absorption. Standing systolic blood pressure increased 27% (P less than 0.05) 2 hr after the same doses of DHE with glyceryl trinitrate. These findings suggest that the extent of first-pass extraction by the liver is the prime determinant of DHE bioavailability after oral administration and that factors that alter gastrointestinal and portal vein flow to the liver affect its bioavailability.

Absorption↗
PubMed1980

Toxicity of Saskatoon serviceberry to cattle.

Saskatoon serviceberry (Amelanchier alnifolia) twigs were administered to cattle in feed rations and by intraruminal dosing to determine the toxicity of the cyanogenic shrub. When chopped twigs were fed as 75% of the diet, cattle exhibited restlessness, shivering, loss of weight, scours and shortness of breath. Low level dosing experiments indicated a rapid turnover of hydrogen cyanide in the rumen. When potential doses were increased to 5 mg hydrogen cyanide/kg (body weight) progressive stages of poisoning developed rapidly, rumen hydrogen cyanide levels were elevated for at least three hours and the increase in heart rate correlated with the rise in blood hydrogen cyanide concentration.

Animals↗
PubMed1979

Noninvasive kinetic approach to the estimation of total hepatic blood flow and shunting in chronic liver disease--a hypothesis.

The intact hepatocyte theory of chronic liver disease suggests a relationship between the degree of shunting of total liver blood flow around the functional liver cell mass and the fraction of functional liver cell mass. By defining this relationship we have developed pharmacokinetic equations to permit the estimation of both total hepatic blood flow and the extent to which this blood flow is shunted. The method requires the determination of the systemic (hepatic) clearances of a high (e.g., indocyanine green [ICG]) and a low (e.g., antipyrine [AP]) extraction ratio drug in the same patient. Applying these equations to literature data obtained from patients with moderate or severe chronic liver disease and from patients with a surgical portacaval shunt, we find: (1) a modest decrease in total hepatic blood flow (16%) and a significant degree of shunting (27%) in patients with moderate chronic liver disease; (2) a substantially reduced total hepatic blood (52%) and extensive shunting (72%) in patients with severe chronic liver disease, and (3) a degree of shunting comparable to that estimated in patients with moderate chronic liver disease but a seriously compromised total hepatic blood flow (a reduction of 55% compared to normal) in patients with surgical portacaval shunts.

Antipyrine↗
PubMed1976

Renin release from isolated rat glomeruli.

1. By the use of a mechanical graded sieving technique a high yield of isolated glomeruli has been obtained from rat kidny. 2. Microscopy and renin assay have shown the presence of renin-containing juxtaglomerular cells attached to these glomeruli. 3. The viability of isolated glomeruli has been confirmed by the ability of the cells to survive and divide in tissue culture and by their exclusion of vital dyes. 4. In superfusion after washout of extracellular renin, the glomeruli actively release constant amounts of renin over 3 h in direct proportion to the number of superfused. 5. Decreasing sodium concentration from 140 to 110 mol/l with constant osmolarity of 305 mosmol/l stimulated renin release by a direct effect on juxtaglomerular cells. 6. Catecholamines stimulated renin release in vitro in proportion to the potency of their action on beta-adrenoreceptors. 7. The system of superfusion of isolated glomeruli provides a technique for studying the influence of mediators leading to renin release acting directly on juxtaglomerular cells, independent of pressure change, tubular sodium, the sympathetic nervous system and circulating hormones.

Animals↗