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Biomedical subjects

R M Reynolds

Publications and source records attributed to R M Reynolds.

18 recordsLinked to original sources
PubMed2005

Cortisol secretion and rate of bone loss in a population-based cohort of elderly men and women.

Although excessive glucocorticoids are a well-recognized cause of osteoporosis, little is known about the role of endogenous glucocorticoids in determining skeletal mass. We have performed a detailed study of the hypothalamic-pituitary-adrenal (HPA) axis to explore the relationships between cortisol secretion and adult bone mass in 151 healthy men and 96 healthy women aged 61 to 73 years. At baseline and 4-year follow-up, bone mineral density (BMD) was measured by dual energy X-ray absorptiometry (DXA) at the lumbar spine and proximal femur; a lifestyle questionnaire was completed; and height, weight, and waist and hip circumferences were measured. At follow-up subjects underwent a very low-dose (0.25 mg) dexamethasone suppression test, a low-dose (1 microg) short synacthen test, and a 24-hour urine collection for measurement of cortisol and its metabolites. In men, elevated peak plasma cortisol was associated with accelerated loss of mineral density in the lumbar spine (r = 0.16, P = 0.05). This relationship remained significant after adjustment for testosterone, estradiol, 25-hydroxyvitamin D, and parathyroid hormone levels (r = 0.22, P = 0.01) and after additional adjustment for age, (BM), activity, cigarette and alcohol consumption, and Kellgren/Lawrence score (r = 0.19, P = 0.03). In contrast in women, elevated peak plasma cortisol was associated with lower baseline BMD at the femoral neck (r = -0.23, P = 0.03) and greater femoral neck loss rate (r = 0.24, P = 0.02). There was no association between plasma cortisol concentrations after dexamethasone or urinary total cortisol metabolite excretion and bone density or bone loss rate at any site. These data provide evidence that circulating endogenous glucocorticoids influence the rate of involutional bone loss in healthy individuals.

Absorptiometry, Photon↗
PubMed2005

The utility of three different methods for measuring urinary 18-hydroxycortisol in the differential diagnosis of suspected primary hyperaldosteronism.

OBJECTIVE: Urine 18-hydroxycortisol (18-OHF) measurements are claimed to discriminate between primary hyperaldosteronism due to Conn's syndrome/adrenal adenoma or idiopathic bilateral adrenal hyperplasia (BAH), and also to identify cases of glucocorticoid-suppressible hyperaldosteronism (GSH). We have evaluated three urine 18-OHF methods using a panel of urine samples from patients with hypertension. DESIGN: Clinical methods comparative study. METHODS: Urine samples from patients with primary hyperaldosteronism due to either adenoma (n = 6), BAH (n = 6), GSH (n = 9), or essential hypertension (n = 38) were analysed without knowledge of the diagnosis using three different methods in different laboratories. These included 'in-house' radioimmunoassay (RIA), 'in-house' time-resolved fluorometric assay (DELFIA), and gas chromatography mass spectrometry (GC-MS). RESULTS: The three assays showed good correlation, but there were large bias differences: RIA bias was greater than DELFIA which was greater than GC-MS. Discrimination between adenoma and BAH patients was best for the DELFIA method, with no overlap between results for these two groups. All three methods gave significantly elevated results for the GSH group compared with the BAH and essential hypertension groups. No assay distinguished BAH from essential hypertension. CONCLUSION: Measurement of urine 18-OHF may be a useful additional test in the differential diagnosis of primary hyperaldosteronism. The clinical diagnostic value of urinary 18-OHF measurements is method-dependent with the DELFIA assay having the best discriminatory value.

Adenoma↗
PubMed2001

Altered control of cortisol secretion in adult men with low birth weight and cardiovascular risk factors.

It has been suggested that increased activity of the hypothalamic-pituitary-adrenal axis may link low birth weight with subsequent development of cardiovascular risk factors and disease. Two hundred and five men, aged 66-77 yr, who were born and still live in East Hertfordshire underwent an overnight very low dose (0.25 mg) dexamethasone suppression test followed by a low dose 1-microgram ACTH-(1-24) stimulation test. A 24-h urine sample was collected for analysis of cortisol metabolites by gas chromatography/electron impact mass spectrometry. Men with lower birth weight had enhanced responses of plasma cortisol to ACTH-(1-24) (P = 0.03), increased total urinary cortisol metabolite excretion (after adjustment for confounding effects of increased obesity and lean body mass in high birth weight men; P = 0.04), but no difference in plasma cortisol after dexamethasone. Features of the metabolic syndrome were independently associated with enhanced adrenal responsiveness to ACTH-(1-24) (raised blood pressure, P = 0.02; glucose intolerance, P = 0.09; hypertriglyceridemia, P = 0.02), with trends to increased urinary cortisol metabolite excretion, but not with differences in plasma cortisol after dexamethasone. Men with low birth weight and/or the metabolic syndrome have increased activity of the hypothalamic-pituitary-adrenal axis. This may be an important mechanism underpinning the effects of events in early life on later cardiovascular disease.

Aged↗
PubMed2001

Elevated plasma cortisol in glucose-intolerant men: differences in responses to glucose and habituation to venepuncture.

Recent evidence suggests that variations in cortisol activity within the physiological range contribute to associations between multiple cardiovascular risk factors. Plasma cortisol measurements during a glucose tolerance test differ in men with hypertension, insulin resistance, and glucose intolerance, but it is unclear whether this reflects altered responses of cortisol to glucose, altered circadian rhythm, or altered habituation to multiple sampling. We performed a single-blind randomized cross-over study comparing 75 g oral glucose with placebo in 39 fasted men (22 glucose intolerant and 17 controls) aged 68-77 yr. In all subjects, plasma cortisol fell during the glucose tolerance test. Subjects with glucose intolerance had significantly higher plasma cortisol following placebo (P = 0.001), suggesting an altered circadian rhythm. Treatment with an oral glucose load blunted the circadian fall in plasma cortisol (P = 0.002), but this response was no different in controls or glucose intolerant subjects. In addition, 0900 h plasma cortisol was higher in the first study phase in controls (P = 0.01) but not in glucose-intolerant subjects (P = 0.18), who showed a lack of habituation to repeated plasma measurements. These data support the hypothesis that alterations in central regulation of the hypothalamic-pituitary-adrenal axis may be important in glucose intolerance.

Aged↗
PubMed2000

Low birth weight predicts elevated plasma cortisol concentrations in adults from 3 populations.

Low birth weight is linked with raised blood pressure in adult life. Recent evidence has suggested that a neuroendocrine disturbance involving the hypothalamic-pituitary-adrenal axis could mediate this link. We therefore investigated the relation between birth weight and fasting plasma cortisol concentrations and the association of cortisol with current blood pressure in population samples of 165 men and women born in Adelaide, South Australia, from 1975 to 1976, 199 men and women born in Preston, UK, from 1935 to 1943, and 306 women born in East Hertfordshire, UK, from 1923 to 1930. Fasting plasma cortisol was measured in plasma samples obtained between 8 and 10 AM. Blood pressure was measured with an automated sphygmomanometer. Low birth weight was associated with raised fasting plasma cortisol concentrations in all 3 populations. A combined analysis that allowed for differences in the gender composition, age, and body mass index between the studies showed that cortisol concentrations fell by 23.9 nmol/L per kilogram increase in birth weight (95% CI 9.6 to 38.2, P<0.001). Fasting plasma cortisol concentrations also correlated positively with the subjects' current blood pressure. However, the association between cortisol and blood pressure was most marked in subjects who were obese (P=0.038 for interaction between body mass index and cortisol, P=0.01 for interaction between waist-to-hip ratio and cortisol). These results show that low birth weight is associated with raised fasting plasma cortisol concentrations. Increased activity of the hypothalamic-pituitary-adrenal axis may link low birth weight with raised blood pressure in adult life.

Adult↗
PubMed1998

Reproducibility of the low dose dexamethasone suppression test: comparison between direct plasma and salivary cortisol assays.

BACKGROUND: The low dose dexamethasone suppression test (DST) has been used to detect subtle variations in the feedback suppression of the hypothalamic-pituitary-adrenal axis, which may contribute to the pathogenesis of several diseases including depression, the metabolic syndrome and coronary artery disease. Little is known about the reproducibility of this test, or whether the test can be combined with analysis of salivary cortisol which would offer a significant advantage over plasma in population studies. SUBJECTS AND DESIGN: A low dose DST was carried out in 29 healthy subjects (14 men, 15 women), aged 24-54 (mean 35.1) years, on two separate occasions 1-10 weeks apart. Following the administration of 0.25 mg dexamethasone (DXM) at 2200 h, plasma and saliva were sampled at 0830 h the next day. Cortisol was measured by radioimmunoassay in plasma and time-resolved immunofluorescent assay ('DELFIA') in saliva. Bland-Altman plots were produced for post-DXM plasma and salivary cortisol measures and used to derive a coefficient of repeatability for each measure, which describes the range of cortisol measurements within which 95% of repeated measurements will fall. RESULTS: The baseline, pre-DXM cortisol concentrations were far more variable for saliva (mean 16.5, range 4.4-34 nmol/l) than for plasma (mean 407.5; range 232-958 nmol/l). Following DXM both measurements showed an approximately 30% suppression from baseline but the variability of salivary cortisol was much greater. From the Bland-Altman plots the 95% range for the differences about their mean was calculated and used as an indication of repeatability. For plasma 95% of differences were within 0.78 log units, indicating that a repeated measurement was approximately half as small or twice as large as the first. For saliva 95% of differences were within 1.64, indicating that a repeated measurement was approximately five times as small or five times as large as the first. CONCLUSIONS: Assessment of dexamethasone suppression by salivary cortisol measurement is far less repeatable than the use of plasma cortisol. In the context of field studies of dexamethasone suppression, salivary cortisol measurements may only be appropriate for large numbers of subjects.

Adult↗
PubMed1998

Long-term consequences of intrauterine growth retardation.

Recent studies in Europe, North America and the developing world have shown that low birth weight or other indices of abnormal fetal growth in babies born at term are linked with a higher prevalence of raised blood pressure, non-insulin-dependent diabetes and cardiovascular disease in late adult life. These findings have led to the 'fetal origins' hypothesis which proposes that fetal adaptations to an adverse intrauterine environment programme persistent physiological and metabolic changes which predispose to these diseases. The mechanisms are unknown, but evidence from animal studies and preliminary evidence in humans suggest that impaired fetal nutrient supply permanently alters neuroendocrine development in the offspring resulting in long-term changes in the set point of adrenocortical and sympathoadrenal hormonal activity.

Animals↗
PubMed1995

Development of a three-scale MMPI: the MMPI-TRI.

A 60-item short form of the MMPI with very high content validity and items that appear on both the MMPI and MMPI-2 was developed and named the MMPI-TRI. It contains three 20-item scales--the Subjective Distress, Acting-Out, and Psychosis scales. These three scales have excellent internal consistency and sufficient independence from each other. An anxiety and depression group of patients, prison inmate group, and a schizophrenic and other psychotic group had the highest mean scores on Subjective Distress, Acting-Out, and Psychosis, respectively. Correlations with the 13 regular scales of the MMPI and MMPI-2, their content and supplementary scales, and four other psychometric instruments provided very strong evidence for validity. Norms are provided.

Acting Out↗
PubMed1979

Structural biochemistry. 17. Synthesis of tryptophan dipeptides.

Boc-Trp-Leu hydrazide has been found to significantly inhibit growth of the L-1210 and P388 murine lymphocytic leukemias. A series of related tryptophan dipeptides were prepared and found to be devoid of such activity. The tryptophan dipeptides were most conveniently obtained employing the DCCI-NHS peptide bond-forming procedure.

Amino Acid Sequence↗