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Biomedical subjects

J D Few

Publications and source records attributed to J D Few.

At least 37 records · Page 2Linked to original sources

The inhibiting effect of atropine on growth hormone release during exercise.

The effects of atropine upon changes in the circulating levels of growth hormone (GH), cortisol, lactate, glucose, and free fatty acids (FFA) were studied during exercise using both constant and progressively increasing work loads. At low work loads, atropine had no effect upon the changes in either cortisol or lactate levels, but the normal exercise-induced rise in GH was abolished or markedly reduced. At higher work loads, especially when prolonged, the usual rises in cortisol and lactate were enhanced by atropine, but the rise in GH was diminished and delayed. In no circumstances were the changes in FFA or glucose significantly affected by atropine. We regard the effect of atropine upon changes in cortisol and lactate responses as secondary to its cardiovascular effect, but suggest that the inhibition of Gh release may be evidence of a cholinergic mechanism in the control of Gh release during exercise.

Atropine↗

The influence of the infusion of noradrenaline on plasma cortisol levels in man.

1. Noradrenaline was infused into normal resting male subjects for consecutive 20 min periods at 3, 7.5 and 15 microgram min-1. At the end of the 1 hr of noradrenaline infusion, total catecholamine levels were in the range 4-6 microgram l.-1, comparable with those observed in severe exercise. 2. At all rates of infusion there were marked elevations of arterial blood pressure leading to reflex reductions of heart rate. Blood flow in the foot was reduced but blood flow in the calf was unaffected. Following the infusion, blood pressure rapidly returned to normal but the heart rate was raised by some 15 beat min-1 higher than the preinfusion control for at least 90 min. 3. Plasma cortisol tended to decrease slightly during the noradrenaline infusion but in twelve out of seventeen experiments it began to rise 30-75 min after termination of the infusion, reaching values 5-15 microgram 100 ml.-1 higher than those at the end of the noradrenaline infusion. Simultaneous rises in plasma aldosterone level were observed in those experiments in which it was measured. 4. Because of the long delay in the onset of hypercortisolaemia it is suggested that this is initiated not by the noradrenaline levels per se but by some physiological readjustments to the rapid fall in plasma noradrenaline level when the infusion was discontinued. The nature of these changes was not determined. 5. It is concluded that the elevated levels of plasma noradrenaline observed during exercise are not responsible for the synchronous increases in cortisol secretion.

Adrenocorticotropic Hormone↗

Plasma cortisone in man: its determination, physiological variation, and significance.

In a method for the simultaneous determination of cortisone, cortisol, and corticosterone, the extracted steroids are separated using paper chromatography and assayed by competitive protein binding. Evidence of the reliability of the method, particularly with respect to the determination of cortisone, is presented. Only trivial changes in cortisone level were detected in response to exercise, surgery, and ACTH, even though marked changes in cortisol level were simultaneously recorded. It is suggested that the inertia in plasma cortisone level may be related to its lesser degree of binding to plasma proteins, relative to cortisol, which would permit more rapid hepatic uptake and possible accumulation of a large extravascular pool of cortisone.

Adrenocorticotropic Hormone↗

Investigation of the secretion and metabolism of cortisol during a 100 km race using [4-14C] and [11 alpha-3H] cortisol.

A mixture of [11 alpha-3H] and [4-14C] cortisol was administered orally to healthy men, following which urine was collected for 24 h. Four subjects acted as basal controls, going about their normal (sedentary) work; a further 3 resting subjects also received 100 mg cortisol orally (high cortisol controls) and 6 subjects competed in a 100 km race. Decreases in the carbon-14 specific activity of the cortisol metabolite excreted by the runners suggested that they secreted cortisol at 2-4 times the rate of the basal controls. This change was mirrored by the excretion of urine free cortisol but not by that of 17-hydroxycorticosteroids. The isotope ratio (3H:14C) of 11-hydroxy metabolites of cortisol from the runners was intermediate between those of the basal and high cortisol controls, from which we conclude that though the fractional oxidation of cortisol to cortisone is reduced by increasing the cortisol pool, it is not affected by exercise per se. This and other results show that although continuous running for 6-8 h, involving energy expenditure in excess of 25 megajoules, leads to a moderate increase in the rate of cortisol secretion, running per se does not appear to markedly affect the metabolism of cortisol.

17-Hydroxycorticosteroids↗

Secretion and metabolism of cortisol and aldosterone during controlled hyperthermia.

1. The rates of secretion and metabolic clearance of cortisol and aldosterone in response to passive heating have been investigated in fifteen young men by the controlled hyperthermia technique combined with continuous I.V. infusion of [14C]cortisol and [3H]aldosterone. 2. During a 1 hr period of elevation of deep body temperature to 38.0 degrees C mean hepatic blood flow measured by indocyanine green clearance decreased by more than 25% compared with normothermic condition. 3. The pattern of response in hyperthermia involved decreasing plasma specific activities indicating increased adrenal secretion of both cortisol and aldosterone. 4. Aldosterone metabolic clearance rate usually decreased in hyperthermia when there was little change in the clearance rate of cortisol, but an increased aldosterone clearance rate was observed when there were significant increases in the clearance rate of cortisol. A contributing factor to elevation of plasma aldosterone concentration in the heat is the reduction in hepatic blood flow which reduces aldosterone metabolic clearance rate. 5. Suppression of the thermally induced rise in plasma cortisol concentration by dexamethasone was associated with a decrease in aldosterone clearance rate which may reflect increased availability of aldosterone-binding plasma protein. 6. Marked rises in plasma cortisol were always accompanied by simultaneous rises in aldosterone, but rises in aldosterone sometimes occurred in the absence of a rise in cortisol. We therefore suggest that ACTH stimulation plays an important, but not exclusive, role in the stimulation of aldosterone secretion during hyperthermia.

Aldosterone↗

Some physiological factors affecting the binding of cortisol by human plasma proteins.

Steady-state gel filtration has been used to study the binding of cortisol to human plasma proteins in vitro. Raising the temperature from 37 degrees C to 41 degrees C results in the mean proportion of free (non-protein-bound) cortisol rising approximately from 7% to 11%. Addition of cortisol to plasma identical to 275 nmol/l) also increased the proportion of free cortisol by approximately 50%. Cortisone is less strongly bound to plasma proteins than cortisol. The mean values (+/- S.D.) for five samples were free cortisol 8.4 +/- 1.1% and free cortisone 26.0 +/- 3.8%.

Blood Proteins↗

Effects of beta blockade and atropinisation on plasma catecholamine concentration during exercise.

The changes in plasma catecholamine concentration (deltaC) following beta-blockade (practolol, 15 mg) and atropinisation (Atropine, 1.8 mg) have been studied on 5 healthy male subjects during exercise on a motor driven treadmill. The results showed that for a given V-2 and % VO2 max, beta blockade was without effect on delta C (except in one athletic subject, but atropine produced a rise in deltaC. In relation to Q, both drugs produced an increase in deltaC, but for a given cardiac frequency (fH) deltaC was higher with beta blockade, and lower with atropinisation than found in control experiments. The intra- and inter-subject variability of delta C in relation of fH was resolved by considering the change in cardiac frequency calculated from baseline value obtained during walking at 6.44 km/h on the level, and expressed as a percentage of the maximal fH attainable for given individuals under the different drug and control conditions (%deltafH). It was concluded that during short term exercise, the rise of deltaC in relation to %deltafH reflects both the myocardial sensitivity to vagal and beta blockade, and the circulatory vasoconstrictor control of blood vessels which is required to sustain increases in systemic and muscle blood flow.

Adult↗

Reliability of plasma cortisol determination by a simple competitive protein binding method.

The method investigated used (3H) cortisol as the ligand, diluted human plasma as the binding protein, and florisil to separate free and bound cortisol. The precision and specificity were found to be adequate for routine use. The effects of such factors as delay in separation of plasma, storage of plasma, provenance of the binding protein, venepuncture, and venous occlusion have been studied. The extent and significance of short term, inter-daily, and longer term variation in plasma cortisol level are discussed.

Humans↗

Pituitary-adrenal response to static exercise in man.

1. Changes in plasma concentrations of catecholamines and cortisol were measured before and after static exercise performed by the subject pushing with both legs against a strain-gauge bar. No marked changes in plasma catecholamine were observed but plasma cortisol increased after the subject pushed for 3 min at 50% of maximum force. 2. Holding a 20 kg weight for 5 min in one hand caused a rise in plasma cortisol and in plasma ACTH but no changes in growth hormone were observed.

Adrenocorticotropic Hormone↗