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Biomedical subjects

J D Few

Publications and source records attributed to J D Few.

At least 19 recordsLinked to original sources
PubMed1991

Investigation of the salivary 18-hydroxycorticosterone:aldosterone ratio in man using a direct assay.

A method for the direct determination of 18-hydroxycorticosterone (18OHB) in human saliva has been developed and validated. Saliva was collected at 30 min and 1 h intervals between 0600 and 2200 h from healthy men and women for the determination of 18OHB (SHB), aldosterone (SA) and glucocorticoids (SGC = cortisol + cortisone). SHB was highly correlated with SA (r = 0.75; P less than 0.001) but even more highly with SGC (r = 0.89; P greater than 0.001). Multiple regression analysis confirmed that SGC was a more important determinant of SHB than was SA. Though the concentrations of 18OHB and aldosterone were highly correlated there was considerable variation in the 18OHB:aldosterone ratio during the period of saliva collection. This ratio tended to be highest in the morning and lowest in the evening and was weakly correlated with SGC level (r = 0.62; P less than 0.01). The 18OHB:aldosterone ratio in saliva approximates to, and is highly correlated with, that in plasma. We suggest that the fluctuations in SHB:SA ratio correspond to the relative rates of secretion of 18OHB and aldosterone and that this ratio is modulated either by ACTH or by cortisol. Whether this indicates that 18OHB is a by-product of glucocorticoid as well as aldosterone metabolism, or whether this implies a separate physiological role for the steroid remains to be clarified.

18-Hydroxycorticosterone↗
PubMed1989

The effect of high altitude on saliva aldosterone and glucocorticoid concentrations.

Saliva was collected from six healthy young men at hourly intervals at sea level and after 1-2, 8-9 and 15-16 days at 4450 m on Mount Kenya for measurement of aldosterone (SA) and glucocorticoid (SGC, cortisol + cortisone) concentrations. Blood samples were collected simultaneously with some of the saliva samples and analysis of these showed that plasma and saliva concentrations of aldosterone and glucocorticoids were highly correlated (r = 0.91 and 0.75 respectively; p less than 0.01 for both hormones). Mean SA for the group was reduced to approximately 50% of the sea-level value (p less than 0.05) by the time the first saliva samples were collected at altitude, and remained at this depressed level throughout the 2-week period on Mount Kenya, although there was considerable inter-subject variation. SGC concentration also tended to be lower on Mount Kenya than at sea level. Though SA was lower throughout the day at altitude compared to sea level, the principal difference in the temporal pattern of SA was the reduction or complete absence of the marked rise in SA that normally occurs in the first few hours after rising. SA and SGC responses to exercise, which consisted of stepping on and off and 0.4-m high stool 60 times/min for 25 min, were assessed at sea level and after various periods at 4450 m.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Aldosterone is secreted intermittently during pregnancy.

Saliva aldosterone concentration was measured in samples collected at hourly intervals from healthy pregnant women (approximately 26 and 36 weeks gestation) who were going about their normal daily activities, and from some women hospitalized for disorders of pregnancy. In the healthy women diurnal saliva aldosterone fluctuated considerably, the highest values being 2-22 times the lowest on a given day. Because of the known correlation between saliva and plasma aldosterone concentrations we believe that the fluctuating salivary level is indicative of fluctuating plasma levels and that this is due to the intermittent secretion of aldosterone. The rate of decline of saliva aldosterone from peak levels indicated a half life (t 1/2) of 72 (SD 31) min which was not significantly different from that in non-pregnant subjects. The temporal pattern of saliva aldosterone suggests an enhanced response of the zona glomerulosa to the factors that cause aldosterone secretion to fluctuate in non-pregnant subjects, rather than the development of a more potent stimulus to the zona glomerulosa during pregnancy. In addition to hour-to-hour variation there is also substantial day-to-day variation, so that estimation of aldosterone in a single sample of saliva or plasma is of little value during pregnancy. The mean diurnal aldosterone concentration can be estimated from five saliva samples so this measurement presents a convenient technique for the assessment of aldosterone status in pregnancy. In contrast to healthy pregnancy, a patient with pre-eclampsia at 39 weeks gestation showed no elevation of saliva aldosterone above non-pregnant levels at any time during the day.

Aldosterone↗
PubMed1988

The determination of 18-hydroxycorticosterone in saliva and plasma: comparison with aldosterone and glucocorticoids.

A radioimmunoassay (RIA) for 18-hydroxycorticosterone (18OHB) is described using antibodies raised against 18OHB-3-CMO conjugated to bovine albumen and an iodine-125 labelled ligand. Extracts of plasma and saliva required thin-layer chromatographic purification prior to RIA. These assays have been validated in terms of precision, accuracy and specificity. The concentration of 18OHB in saliva is approx 20% of that in plasma and the two values are correlated. Thus, in a series of 20 healthy subjects the saliva and plasma concentration were 169 +/- 92 and 904 +/- 621 pmol.l-1 respectively with r = 0.72 (P less than 0.001). When the diurnal patterns of 18OHB, aldosterone and glucocorticoid (cortisol + cortisone) concentrations in saliva were investigated the patterns of 18OHB and aldosterone were usually similar though the 18OHB:aldosterone ratio can vary considerably. These and similar data suggest that the secretion of 18OHB and aldosterone are not completely synchronous. Our results show that saliva is a suitable body fluid in which to estimate 18OHB concentration and this measurement gives a useful reflection of the plasma 18OHB concentration. This technique should facilitate the investigation of the physiological role of this compound.

18-Hydroxycorticosterone↗
PubMed1987

Diurnal fluctuation in saliva aldosterone concentration.

We have measured saliva aldosterone concentration (SA) at frequent intervals in subjects going about their normal daytime activities. Four hourly sampling sufficed to give a reasonable estimate of mean diurnal SA but hourly sampling is necessary if it is desired to study the temporal pattern of SA. In subjects with normal or elevated mean levels, SA fluctuated considerably suggestive of several distinct episodes of aldosterone secretion. Such fluctuations show little correlation with the concentrations in saliva of glucocorticoids (cortisol + cortisone) nor are they consistent with a circadian rhythm of aldosterone secretion. We suggest that they may represent responses to such stimuli as eating, drinking or physical activity, and possibly to other as yet unidentified factors. These observations show the importance of comprehensive diurnal assessment of aldosterone level in physiological and pathological investigations. Because of its non-invasive nature and the high productivity of the assay, measurement of SA is ideally suited for this purpose.

Aldosterone↗
PubMed1986

The regulation of the biologically available fractions of oestradiol and testosterone in plasma.

The albumin bound fractions of oestradiol and testosterone have been measured in samples of plasma obtained over a 24 h period from women with breast cancer or polycystic ovarian disease and from pre- and postmenopausal control subjects and related to plasma levels of free fatty acids. For most subjects changes in the fraction of oestradiol bound to albumin were related to changes in plasma levels of free fatty acids. A significant decrease in the albumin bound testosterone fraction during the night was associated with increased plasma levels of cortisol.

Biological Availability↗
PubMed1986

Effects of packed cell volume reduction on renal haemodynamics and the renin-angiotensin-aldosterone system in patients with secondary polycythaemia and hypoxic cor pulmonale.

Polycythaemia was corrected by erythrapheresis in ten patients with hypoxic cor pulmonale who were stable on regular diuretic therapy. Renal haemodynamics, renal function and the renin-angiotensin-aldosterone system were assessed before and afterwards. Before erythrapheresis effective renal plasma flow (ERPF) was reduced (63% predicted) but glomerular filtration rate (GFR) was preserved (88% predicted) by a rise in filtration fraction (FF) (138% predicted). A negative correlation existed between ERPF and packed cell volume (r = -0.723; P less than 0.02) and also between ERPF and PaCO2 (r = -0.710; P less than 0.05). Polycythaemia was sufficient to maintain renal oxygen delivery (97% predicted). After erythrapheresis systemic blood pressure, blood volume and blood viscosity all decreased. ERPF increased by 18% (P less than 0.02). FF fell by 11% (P less than 0.05) and GFR was unchanged. Renal oxygen delivery diminished by 25% (P less than 0.001). Plasma renin activity was increased in five patients and plasma aldosterone increased in two patients before erythrapheresis. No sustained fall occurred in plasma renin activity or plasma aldosterone, possibly because the haemodynamic consequences of the procedure had opposing actions on renin secretion. Although the reduction in FF would per se tend to enhance renal sodium and water excretion, a diuresis or natriuresis did not occur consistently.

Aged↗
PubMed1986

The relationship between salivary aldosterone and plasma free aldosterone concentrations.

The proportion of aldosterone in plasma not bound to proteins (% plasma free aldosterone, %PFA) was measured using an equilibrium dialysis technique and was found to lie predominantly in the range 25-40% although extremes of 20% and 60% were encountered. From this value and the total concentration of aldosterone in plasma (plasma aldosterone, PA) the concentration of free aldosterone in plasma (PFA) was calculated. Percentage PFA was not affected by the in-vitro addition of aldosterone (up to the equivalent of 2000 pmol/l) but the incremental addition of cortisol (up to the equivalent of 550 nmol/l) resulted in a linear increase in % PFA from 26% to 34%. Percentage PFA was found to be significantly, negatively correlated with serum albumin concentration (r = -0.87; P less than 0.001) but it was only when this was less than 15 milligrams that % PFA was abnormally high. Salivary aldosterone concentration (SA) was more highly correlated with PFA (r = 0.84) than with PA (r = 0.75), which indicates that even modest variance in %PFA has a discernible effect upon the overall SA-PA relationship. We conclude that measurement of salivary aldosterone concentrations gives a useful estimate of plasma free aldosterone level. Variations in the latter are determined more by changes in the total concentration of aldosterone in plasma than by variations in the degree of binding by plasma proteins.

Albumins↗
PubMed1986

The relation between aldosterone concentrations in plasma and saliva during pregnancy.

The concentrations of aldosterone and glucocorticoids (cortisol + cortisone) were measured in saliva and plasma samples obtained from healthy women during early (11-19 weeks), mid (24-29 weeks) and late (32-37 weeks) pregnancy. There was a progressive increase in mean aldosterone levels in both saliva and plasma throughout pregnancy, though at each stage of pregnancy the range was very wide. Glucocorticoid levels increased up to mid-pregnancy and then remained constant. At no stage were aldosterone and glucocorticoid levels significantly correlated. The proportion of free (non-protein bound) aldosterone in plasma, and the saliva:plasma ratio of aldosterone did not differ from the non-pregnant range at any stage of pregnancy. We conclude that measurement of aldosterone concentration in saliva is a convenient and valid method for the estimation of plasma free aldosterone in pregnancy and so provide a non-invasive technique for assessing aldosterone status throughout pregnancy.

Aldosterone↗
PubMed1986

Saliva aldosterone concentration in healthy infants.

Aldosterone and glucocorticoid (cortisol + cortisone) concentrations were measured in 106 saliva samples from healthy infants. Most aldosterone values fell within the adult range (0-0.15 nmol/l (0-5.4 micrograms/100 ml)), but 10 were greater than 0.2 nmol/l (7.2 micrograms/100 ml). Aldosterone concentration was not related to sex, ethnic origin, time of collection, distress, or cortisol concentration but decreased with age.

Adult↗
PubMed1985

The effect of exercise on the production and clearance of testosterone in well trained young men.

Tritium-labelled testosterone was infused into four well-trained subjects at rest and during one hour of exercise at about 60% of their maximum aerobic power. This exercise regime led to a mean increase of 27% (range 10-51%) in plasma testosterone concentration. At the same time there were significant decreases in the estimated hepatic plasma flow (EHPF) (45%; range 28-67%), metabolic clearance rate of testosterone (MCRT) (29%; range 18-37%) and plasma volume (8.2%; range 3-10%). The production rate of testosterone decreased by 10% (range 9-22%) but this was not statistically significant. The ratio MCRT:EHPF increased in 3 out of 4 subjects in response to exercise but there was considerable inter-subject variation both at rest and during exercise. These findings suggest that the exercise-induced elevation of testosterone level is due solely to the reduction in the rate at which testosterone is cleared from the plasma. The principal cause of the reduction in MCRT is probably the reduction in EHPF but the variation in the ratio MCRT:EHPF suggests that changes in the extrahepatic clearance of testosterone may also be involved.

Adult↗
PubMed1985

Adrenocorticosteroids: chemistry, synthesis and disturbances in disease.

The biosynthesis of adrenocortical steroids is now a reasonably well understood process, which proceeds by discrete, enzyme directed steps from cholesterol to the various hormonal steroids. However, much of our knowledge derives from studies of animal tissues and there is a need for further studies of human glands. In particular, the details of individual enzyme systems, and the extent and significance of compartmentalization of steroid intermediates requires further exploration. The adrenal metabolic errors also merit further study, to clarify some aspects of congenital adrenal hyperplasia and to explain the relationship between biochemical and clinical observations. The advent of immunoassay methods for the measurement of steroid hormone levels in plasma has changed the approach to diagnostic steroid endocrinology, with less emphasis now on the measurement of urinary steroid metabolites, particularly in regard to androgens. The newer and sensitive methods available also allow the assay of steroid hormones in saliva, and the ready availability of this fluid, and the fact that sampling is a non-invasive technique makes salivary steroid assay an attractive alternative to other, traditional methods of investigation requiring blood or urine collection. Inhibitors of steroid biosynthesis and of steroid action have been used with considerable success in diagnostic techniques and to a limited extent in the treatment of steroid disorders. As our understanding of the details of steroid biosynthesis, mechanism of steroid action, and control of steroid secretion improve, further progress in designing clinically useful inhibitors should be possible.

3-Hydroxysteroid Dehydrogenases↗
PubMed1984

Neural-tube defects produced in Syrian hamsters by potato glycoalkaloids.

Keeler et al. (78) showed that potato sprouts could be teratogens for the central nervous system in the Syrian hamster. We demonstrate here the same teratogenic effect from a British cultivar, Arran Pilot. Most of the activity was traced to the two solanidine triglycosides, alpha-chaconine and, at a higher dose level, alpha-solanine. Some possible implications for the study of human neural-tube defects are considered.

Abnormalities, Drug-Induced↗
PubMed1984

Thyroid and adrenal responses of ducks (Anas platyrhynchos) during saline adaptation.

Fresh water-reared Aylesbury ducklings were given 0.1 or 0.2 M NaCl drinking water and variations in the plasma concentrations of thyroxine (T4), triiodothyronine (T3), corticosterone, and aldosterone were determined. Within 24 hr of being transferred to 0.2 M NaCl the corticosterone concentration was increased, whereas the levels of plasma T3 and aldosterone were reduced. The increase in corticosterone secretion persisted for at least 7 days, but the T3 and aldosterone concentrations had returned to control levels within 5 days. The concentrations of plasma aldosterone and T3 were similarly affected in birds transferred to 0.1 M NaCl, although corticosterone levels increased only after the birds were maintained on 0.1 M NaCl for 7 days. Plasma concentrations of T4 were increased in 1- to 2-week-old (but not 7-week-old) birds 7 days after their transfer to 0.1 and 0.2 M NaCl. In birds maintained on saline for 6 weeks the basal concentration of each hormone was not significantly different from that in fresh water-reared controls. When saline-reared birds were returned to freshwater conditions the plasma aldosterone and T3 concentrations were increased over a 5-day period. Transfer to saline consistently reduced body weight and food intake, whereas the transfer of saline-reared birds to fresh water stimulated body weight gain. Consequently, although these endocrine responses during saltwater adaptation might be expected to minimise the loss of body reserves and to facilitate the extra renal excretion of sodium, these alterations in endocrine function may be partly due to salt water-induced changes in food intake.

Adaptation, Physiological↗
PubMed1984

The direct determination of aldosterone in human saliva.

A method is described for the direct radioimmunoassay of aldosterone in human saliva without preliminary extraction or chromatographic purification. The method has been validated with respect to sensitivity, accuracy, precision, specificity and other criteria. Under basal conditions concentrations of aldosterone in saliva ranged from 10-63% those of plasma (mean +/- SD = 32.5 +/- 13.1%). When plasma aldosterone responded to such acute stimuli as postural change, exercise or ACTH infusion, this was promptly reflected in corresponding changes in saliva aldosterone concentration. In subjects going about their normal daily business saliva aldosterone concentration fluctuated markedly during the day. It is therefore difficult to define a normal range for saliva aldosterone concentration but present observations suggest an upper limit of 150 pmol/l under basal conditions.

Aldosterone↗
PubMed1982

Kinetics and retention of solanidine in man.

1. When [3H]solanidine was administered to normal human subjects by i.v. injection, the tritium concentration in the erythrocytes was 2-5 times greater than in the plasma. Three phases in the clearance of tritium from the plasma were identified having half-times of 2-5 min, 120-300 min and 70-105 h. 2. Rates of excretion of 3H in urine and faeces were low: 24 h after administration, 1-4% of the dose of 3H had been excreted in urine and 1-3% in faeces. During the following week the combined rates of excretion were about 2% a day. 3. Solanidine has been detected in human post-mortem liver and its identity confirmed by mass spectroscopy. 4. These data show that solanidine is absorbed from the diet and stored in the body for prolonged periods of time. We suggest that at times of increased metabolic stress (pregnancy, starvation, debilitating illness), stored solanidine might be mobilized from innocuous loci with deleterious effects.

Diosgenin↗
PubMed1980

Adrenocortical response to one-leg and two-leg exercise on a bicycle ergometer.

Twelve healthy male subjects exercised for 30 min on a bicycle ergometer, using only one leg, at a work load that was nearly exhausting. Nine subjects (group A) showed a marked rise in plasma cortisol concentration (240 +/- 50 nmol x l-1), but in three subjects no such rise occurred (group B). All group B subjects had elevated cortisol levels prior to the period of exercise, which may have inhibited the adrenocortical response. Seven subjects of group A also performed the same work load using both legs. Under this regime, increases in plasma cortisol and aldosterone levels, blood lactate level and heart rate, but not plasma potassium, were significantly smaller than for one-leg exercise. These findings are consistent with the hypothesis that activation of the hypothalamic-pituitary-adrenal (HPA) system during exercise could be mediated through the stimulation of chemoreceptors in the exercising muscles. This effect could be reinforced by HPA stimulation in response to the greater acceleration of heart rate in one-leg exercise. The marked rises in plasma potassium levels might be responsible for the elevation of plasma aldosterone concentration particularly in those experiments when this occurs earlier than, or in the absence of, rises in cortisol concentration.

Adult↗