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Biomedical subjects

R Fraser

Publications and source records attributed to R Fraser.

At least 253 records · Page 14Linked to original sources
PubMed1986

Dopamine effects on adrenocorticotrophin-stimulated aldosterone, cortisol, corticosterone and 11-deoxycorticosteroid concentrations in sodium-replete and sodium-deplete man.

The effect of dopamine (1 microgram/kg per min) on corticosteroid response to ACTH (0.1, 1 and 10 ng/kg per min) was compared with that of a placebo in sodium-replete (150 mmol/day) and -deplete (10 mmol/day) normal man. Dopamine had no effect on aldosterone, cortisol or corticosterone responses in either dietary phase, but increased deoxycorticosterone (897.0 +/- 126.4 (S.E.M.) vs 590.0 +/- 84.3 pmol/l, normal Na+; 1264.2 +/- 84.3 vs 764.5 +/- 84.3 pmol/l, low Na+) and deoxycortisol (6.033 +/- 0.583 vs 5.048 +/- 0.680 nmol/l, normal Na+; 5.112 +/- 0.600 vs 4.130 +/- 0.367 nmol/l, low Na+) levels during ACTH administration (all P less than 0.01). Deoxycorticosterone and corticosterone responses to ACTH were greater during sodium depletion than repletion (both P less than 0.01). Dopamine therefore increased 11-deoxycorticosteroid concentrations during ACTH-stimulated steroidogenesis. This may reflect action of dopamine to increase extra-adrenal formation of 11-deoxycorticosteroids.

Adrenal Cortex Hormones↗
PubMed1986

The liver sinusoidal cells. Their role in disorders of the liver, lipoprotein metabolism and atherogenesis.

A review of the morphological and metabolic interactions between hepatocytes, the various sinusoidal cells and sinusoidal blood is presented. This field of investigation is rapidly expanding, with widespread implications in the regulation of physiological processes and diseases in the liver and other organs. Although most of the review is of already published work, some areas incorporate personal speculations of the probable role of sinusoidal cells in disease processes.

Alcoholism↗
PubMed1986

Ultrastructural studies of the portal transport of fat in chickens.

Dietary fat is transported in the chicken by portomicrons; these large lipoproteins enter the portal blood of the small intestinal villi. We have shown by electron microscopy that avian portomicrons resemble mammalian chylomicrons in size, but their mode of transport differs. Portomicrons enter the intestinal blood vessels through endothelial intracytoplasmic vesicles, whereas chylomicrons enter the intestinal lymphatics through gaps between endothelial cells. We have also shown that the sinusoidal endothelium of the chicken liver, like that of the mammal, is fenestrated. Because the fenestrae are relatively few in number, the endothelium is less porous in the chicken than in the rat. We postulate that this prevents the hepatocytes from being swamped by dietary fat, but makes the chicken susceptible to diet-induced atherosclerosis.

Animals↗
PubMed1985

The role of calcium ions in the mechanism of ACTH stimulation of cortisol synthesis.

Removal of free calcium ions from the incubation medium of isolated bovine adrenocortical cells with EGTA reduced basal cortisol synthesis and blocked the effects of ACTH; additional calcium restored normal steroid synthesis. Calcium channel blockers, verapamil and nitrendipine and the calmodulin antagonist, trifluoperazine inhibited ACTH-stimulated cortisol synthesis in a dose-dependent manner (IC50s of 6.2, 10 and 5.2 microM, respectively). Steroidogenic effects of dibutyryl cyclic AMP were prevented with 50 microM verapamil or trifluoperazine. Calcium ionophore A23187 at 1 microM increased cortisol synthesis 2-3 fold which was less than the normal response to ACTH. Stimulatory effects of ionophore and cyclic AMP or ACTH were not additive. ACTH-stimulation of cortisol synthesis appears to involve cyclic AMP-dependent uptake of extracellular calcium ions, possibly by a mechanism requiring calmodulin. Increases in intracellular calcium ions cannot wholly mimic ACTH actions.

Adrenal Cortex↗
PubMed1985

Effect of induction of anaesthesia with etomidate on corticosteroid synthesis in man.

The effects of a single bolus dose of etomidate 0.3 mg kg-1 or thiopentone 5 mg kg-1, on the synthesis of corticosteroid hormones and adrenocorticotrophic hormone (ACTH), were compared for 24 h in 12 patients, undergoing minor surgery under general anaesthesia. Following opioid premedication i.m. and general anaesthesia, plasma cortisol concentrations decreased transiently within the first hour of anaesthesia in all 12 patients. The six patients who received etomidate had statistically higher plasma 11-deoxycorticosterone concentrations at 4 and 24 h than those who had received thiopentone (P less than 0.01). Throughout the study, no difference in plasma cortisol, corticosterone or ACTH concentrations were found between the two groups. We have demonstrated a biochemical effect of a single bolus dose of etomidate consistent with incomplete inhibition of adrenocortical mitochondrial 11 beta-hydroxylase activity, but no clinically significant adrenocortical suppression.

Adrenal Cortex Hormones↗
PubMed1985

Comparison of the effects of etomidate, thiopentone and propofol on cortisol synthesis.

The inhibitory effects of etomidate, thiopentone and propofol on basal and ACTH-stimulated cortisol synthesis by isolated bovine adrenocortical cells have been examined. Concentrations required for 50% inhibition of ACTH-stimulated cortisol output were 1.1 X 10(-4) mol litre-1 for propofol, 3 X 10(-5) mol litre-1 for thiopentone and 4.6 X 10(-1) mol litre-1 for etomidate. At concentrations likely to be achieved during anaesthesia, etomidate would block cortisol output by isolated cells, thiopentone might slightly reduce output and propofol would be unlikely to alter cortisol synthesis significantly.

Adrenal Cortex↗
PubMed1985

A dose-response study of HOE 498, a new non-sulphydryl converting enzyme inhibitor, on blood pressure, pulse rate and the renin-angiotensin-aldosterone system in normal man.

The effect of different oral doses of HOE 498, a new non-sulphydryl containing converting enzyme inhibitor, was investigated in a double-blind, placebo-controlled study in normotensive volunteers. Dose-related reductions in serum converting enzyme activity, plasma angiotensin II and aldosterone were seen, greater at 4 h than at 12 h after drug ingestion. Converse dose-related increases in blood angiotensin I and plasma active renin concentration occurred. Falls of angiotensin II were as great with 20 mg as with 50 mg of HOE 498, although the effect was more prolonged with 50 mg. The reductions in concentrations of plasma angiotensin II and serum converting enzyme activity and the increases in plasma renin concentration were correlated with the concentration of HOE 498 - diacid in plasma. Dose-related falls in both supine and erect blood pressure were maximal 2-3.5 h after dosing. Pulse rate increased marginally but insignificantly in the supine; slightly and significantly in the upright position, concomitantly with the blood pressure reduction at all doses of active drug. We conclude that effects of single doses of HOE 498 on the renin-angiotensin system are maximal within 4 h, but are still apparent after 24 h. Thus it is likely that once daily administration will be adequate for treatment of high blood pressure in patients.

Administration, Oral↗
PubMed1985

Peripheral mucociliary clearance with high-frequency chest wall compression.

We investigated the effects of high-frequency chest wall compression (HFCWC) on peripheral and tracheal mucus clearance in anesthetized spontaneously breathing dogs. HFCWC was achieved by oscillating the pressure in a thoracic cuff with a piston pump. Regional lung retention of a technetium-99m sulfur colloid aerosol was monitored with a gamma camera. A peripheral mucus clearance index (PMCI) was defined for each region of interest. The tracheal mucus clearance rate (TMCR) was determined by bronchoscopic visualization of marker particle transport. Phase I: In seven dogs, 30 min of HFCWC at 13 Hz with peak cuff pressure (Pcuff) 100-120 cmH2O was found to significantly enhance PMCI in regions immediately under the cuff. (delta PMCI = 24.4 +/- 4.6 in the basal peripheral region.) Phase II: Because of subpleural hemorrhage in phase I, the effect of HFCWC on TMCR at various Pcuff levels was studied in five dogs. The enhancement of TMCR by HFCWC reached a plateau level at Pcuff = 50 cmH2O. Phase III: HFCWC at 13 Hz with Pcuff = 50-60 cmH2O was found to significantly enhance PMCI in five dogs without the consequence of hemorrhage. Correlations were found between the enhancement of PMCI and TMCR by HFCWC. These results demonstrate that HFCWC is effective in enhancing both peripheral and central mucus clearance in dogs and safe when moderate pressures are applied.

Animals↗
PubMed1985

Potassium fluxes in bovine adrenal cells during adrenocorticotropin stimulation.

Active (ouabain-sensitive) and passive (ouabain-insensitive) fluxes of 43K were measured in isolated bovine zona fasciculata/reticularis cells. ACTH inhibited passive influx in a dose-dependent manner and, at a concentration that maximally stimulated steroidogenesis (10(-8) M), also inhibited passive efflux. ACTH did not affect active potassium transport. Angiotensin II (10(-6) M) and cAMP (10(-2) M) inhibited passive influx to the same extent as did 10(-8) M ACTH. Angiotensin II (10(-6) M) also reduced active potassium uptake, although this did not appear to be related to changes in cortisol biosynthesis. Increases in cortisol synthesis by ouabain-treated cells in response to angiotensin II and ACTH were proportional to decreases in potassium influx. The addition of cortisol (1 microgram/ml) to cells slightly reduced passive potassium uptake, but not to the same extent as did 10(-8) M ACTH. Frusemide, an inhibitor of passive sodium/potassium cotransport, did not wholly abolish the effects of ACTH on potassium influx. These changes in flux are probably related to electrophysiological changes in membrane potential. Their significance in the regulation of ACTH actions has yet to be determined.

Adrenal Glands↗
PubMed1985

Body composition, blood pressure and the renin-angiotensin system in acromegaly before and after treatment.

Serial measurements of exchangeable sodium (Nae), blood pressure, circulating concentrations of growth hormone and the components of the renin-angiotensin-aldosterone system were made in 39 acromegalic patients: 26 patients were studied before and after treatment. Mean Nae was considerably increased, frequently being greater than values found in Conn's syndrome. Nine of the 26 untreated patients were hypertensive (35%) and of these seven were female and over the age of 52 years. In the untreated patients, Nae was positively correlated with age, blood pressure and growth hormone log concentration: the strongest correlation between Nae and growth hormone was obtained when the duration of the acromegalic process was taken into account. Following treatment there was often considerable reduction in Nae and this correlated closely with the fall in growth hormone: the relation between the fall in Nae and fall in blood pressure was less marked. The sodium retaining properties of growth hormone may cause a rise of blood pressure in a susceptible minority of acromegalics.

Acromegaly↗
PubMed1984

Prediction of acute cardiac rejection using radionuclide techniques.

Radionuclide scanning of the donor left ventricle using technetium-99m-labelled red cells was used to monitor acute rejection after heterotopic heart transplantation and compared with histopathological evidence of rejection obtained at examination of an endomyocardial biopsy specimen. The ejection fraction and end-diastolic, end-systolic and stroke volumes were calculated at each examination; an equation was derived from these data to predict the degree of acute rejection, using histopathological examination of endomyocardial biopsy specimens as criteria of the presence and severity of rejection. A highly significant multiple correlation between radionuclide scanning parameters and endomyocardial biopsy was found. The advantages of non-invasive radionuclide scanning over the invasive procedure of endomyocardial biopsy are discussed.

Adolescent↗
PubMed1984

Disorders of the adrenal cortex: their effects on electrolyte metabolism.

The adrenal cortex is an important factor in the control of electrolyte and water balance and in blood pressure homeostasis. Not surprisingly, therefore, hyper- and hyposecretion of one or more of its products has extensive repercussions. Hypersecretion of aldosterone, as seen in primary hyperaldosteronism and related diseases, and of other mineralocorticoids such as corticosterone and/or 11-deoxycorticosterone, as seen in 17 alpha-hydroxylase deficiency or 11 beta-hydroxylase deficiency syndromes, respectively, are associated with hypertension, sodium retention, potassium wastage and a metabolic alkalosis. On the other hand, impaired secretion, as in Addison's disease or in congenital deficiencies of other steroid-synthesizing enzymes, leads to hypotension, sodium loss with hypovolaemia, and hyperkalaemia. In each case, these disturbances of electrolyte metabolism may cause neurological and muscle dysfunction. The relationship between glucocorticoid hypertension and electrolyte metabolism is less clear and the importance of the adrenal cortex in the aetiology of essential hypertension is still being assessed.

Addison Disease↗
PubMed1984

Relation of blood pressure and body sodium content during sodium depletion in normal and hypertensive subjects.

Blood pressure, exchangeable sodium content, sodium metabolic balance, and plasma concentrations of active renin, angiotensin II, and aldosterone were measured in seven normal men and 10 essential hypertensive men of similar age and weight. The measurements were made under two circumstances: during a 2- to 3-day period of normal sodium intake of 145-150 mmol/24 h and during a 2- to 3-day period of sodium depletion produced by 40 mg frusemide and a dietary sodium intake less than 10 mmol/24 h. Mean arterial pressure decreased in nine of the 10 hypertensive subjects but increased in six of the seven normotensive subjects during sodium depletion. Blood pressure changed more for a given change in exchangeable sodium level in hypertensive subjects than in normotensive subjects, despite a similar loss of sodium in the two groups. Changes in blood pressure varied markedly in the hypertensive group. Patients showing the greatest fall in arterial pressure had the least rise in plasma active renin concentration and, not significantly, the least rise in plasma aldosterone level. These findings are compatible with a model of pressure natriuresis which is altered more in normal subjects during changes in dietary sodium content, thereby preventing a rise in arterial pressure. Failure of this compensatory mechanism in hypertensive subjects may raise blood pressure.

Adult↗
PubMed1984

Enalapril (MK421) and its lysine analogue (MK521): a comparison of acute and chronic effects on blood pressure, renin-angiotensin system and sodium excretion in normal man.

The immediate and long-term effects of enalapril (MK421) and its lysine analogue (MK521) in once-daily dosage, were compared in a study of 12 normal subjects. Both compounds lowered blood pressure equally throughout 24 h without causing tachycardia. The biochemical changes with MK521 were more sustained than with MK421, but this did not affect the magnitude of blood pressure reduction. Twenty-four hours after the previous dose, with both active drugs, plasma renin concentration was significantly higher on day 8 than on day 1, though angiotensin I did not increase in proportion; this probably reflects a fall in renin-substrate with prolonged converting enzyme inhibition. There was an early natriuresis with each compound but this effect was no longer apparent after 8 days of continuous therapy. Both MK421 and MK521 were well tolerated with no serious side effects.

Adult↗
PubMed1984

Effect of the 5-hydroxytryptamine type 2 receptor antagonist, ketanserin, on blood pressure, the renin-angiotensin system and sympatho-adrenal function in patients with essential hypertension.

Ketanserin, a 5-HT type 2 receptor antagonist, was administered intravenously to nine patients with essential hypertension in a double-blind placebo controlled study to investigate the drug's effects on blood pressure, heart rate, the renin-angiotensin system and sympatho-adrenal function. Average blood-pressure for the group prior to injection of the drug was 150 +/- 7/94 +/- 4 (s.e. mean) mm Hg and decreased significantly (P less than 0.01) to 137 +/- 8/88 +/- 5 mm Hg during the 2 h after injection; heart rate increased immediately after injection of ketanserin, reaching a maximum of 81 +/- 4 beats/min. After drug administration systolic and diastolic blood pressure decreased on tilting, but the heart rate response was not different from that with placebo. Ketanserin did not affect the blood pressure response to graded infusion of the alpha 1-adrenoceptor agonist phenylephrine. Plasma active renin, angiotensin II and aldosterone concentrations increased slightly but not significantly after the drug; plasma noradrenaline increased transiently. 5-HT may be important in the maintenance of blood pressure but alternative mechanisms for the action of ketanserin in reducing blood pressure require investigation.

Adrenal Glands↗