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Biomedical subjects

R A Donald

Publications and source records attributed to R A Donald.

At least 73 records · Page 4Linked to original sources
PubMed1990

Arginine vasopressin in Cushing's disease.

Bilateral simultaneous blood samples were taken from the inferior petrosal sinuses of nine patients with Cushing's disease for measurement of adrenocorticotropin (ACTH), vasopressin (AVP), prolactin, growth hormone, luteinising hormone (LH), and follicle stimulating hormone (FSH). Inter-sinus gradients for ACTH (range 3.3-18.2) and AVP (2.0-375) correctly lateralised the microadenoma in seven of these patients. One additional patient showed an increased gradient for AVP but not ACTH on the side of the tumour. The correlation between the AVP and ACTH concentrations in the petrosal sinus draining the microadenoma was significant. Petrosal sinus plasma concentrations of prolactin and growth hormone were also significantly higher on the side of the tumour than on the non-tumour side. Evidence against a non-specific tumour effect on the secretion of all pituitary hormones was the fact that in most cases the gradients for LH and FSH were not significant. It is proposed that increased delivery of AVP to part of the pituitary may result from an aberrant blood supply, and that AVP may interact with corticotropin releasing factor to promote tumour growth and ACTH release.

Adenoma↗
PubMed1990

Effects of age and sex on bone density at the hip and spine in a normal Caucasian New Zealand population.

We have studied a normal adult caucasian population (462 females, 264 males age range 20-84) using dual photon absorptiometry to establish patterns of bone reduction at the spine and hip. Subjects were either randomly selected from the electoral roll or volunteers. Bone mineral density reduction at the lumbar spine in females appeared to increase at 40 years and was sustained until 60 years. In males bone mineral density at the spine was preserved. The density at the hip in females decreased throughout adult life beginning before the menopause. In males bone density was preserved at the femoral neck and trochanteric region but not at Wards triangle where reduction occurred throughout life. When compared with other normal populations there was higher bone mineral density at the spine in postmenopausal New Zealand females but no significant difference at the hip.

Absorptiometry, Photon↗
PubMed1990

The assessment of pituitary function.

The assessment of pituitary function can now be carried out quickly and accurately by means of outpatient testing procedures and hormone immunoassays. Improvements in assay methodology have resulted in greater specificity and sensitivity although some technical problems remain. The diagnosis of patients with functioning and nonfunctioning pituitary tumors, hypopituitarism and target gland disorders is discussed with particular reference to diagnostic difficulties and recent advances.

Humans↗
PubMed1990

Aminopropylidine diphosphonate (APD) in mild primary hyperparathyroidism: effect on clinical status.

Mild hypercalcaemia associated with primary hyperparathyroidism has been increasingly recognized with the use of automated biochemical screening. Management is often difficult as symptoms are often absent or non-specific. Accordingly, we employed the hypocalcaemic effect of the diphosphonate APD to assess the effect of an acute fall in plasma calcium on indices of general well being, blood pressure, and vasoactive hormones in patients with mild primary hyperparathyroidism. Ten patients were studied in a randomized single blind, placebo-controlled cross-over study, using 30 mg APD intravenously or control saline infusion, over 2 h. Metabolic measurements, formal tests of muscle strength and cognitive function, and a standardized questionnaire were assessed 7 days after infusions. Albumin corrected plasma calcium was significantly lower (mean 2.49 +/- 0.04 SEM mmol/l) after APD when compared to control values (2.70 +/- 0.06 mmol/l, P less than 0.001). Twenty-four-hour urinary calcium, plasma magnesium and absolute monocyte count decreased significantly, whereas plasma parathyroid hormone increased after APD (P less than 0.05). There was no significant change in hypercalcaemic symptoms, muscle strength or cognitive function, and blood pressure, renin, aldosterone and atrial natriuretic peptide did not change. Side-effects, when they occurred, were mild. It is concluded that APD is a safe and effective means of lowering plasma calcium in mild primary hyperparathyroidism, but these acute reductions are associated with little or no improvement in clinical status in these patients.

Adult↗
PubMed1990

Plasma corticotrophin-releasing factor and vasopressin responses to hypoglycaemia in normal man.

The plasma cortisol, ACTH, AVP and corticotrophin-releasing factor (CRF) responses to insulin-induced hypoglycaemia were investigated in six normal men using a controlled, randomized, cross-over design. Hormonal concentrations were determined following insulin or saline injection. The maximum cortisol response was seen at 90 min while plasma ACTH, AVP and CRF concentrations peaked at 45 min following insulin injection. The responses of the insulin-treated and control groups were compared by assessing the incremental response from baseline (pre-injection) to peak hormone levels. A significant increase was observed for each hormone following insulin injection. The mean of the incremental responses between 30 and 120 min in each subject was also statistically greater for each hormone in the insulin-treated group when compared with the control group. These results are consistent with the hypothesis that AVP and CRF are both physiological mediators of ACTH secretion induced by a hypoglycaemic stress.

Adrenocorticotropic Hormone↗
PubMed1989

The response to treatment with pituitary growth hormone: the New Zealand experience.

Ninety-four growth hormone deficient New Zealand children were treated with thrice weekly intramuscular injections of human pituitary growth hormone (GH) from 1979 to 1985 and the results from 43 children were analysed in detail. Their height velocity was mean (SD) 4.0 (1.9) cm/yr immediately prior to treatment and 8.5 (3.1) cm/yr in the first year of treatment. In each of the first three years of treatment the height velocity was significantly increased (p less than 0.001), but there was a significant decline in height velocity between the first and second, and second and third years. Nevertheless each year of treatment gave a highly significant gain in relative height. Bone age did not advance more rapidly than chronological age during the first two years of treatment, but did so subsequently. The response to GH, as assessed by the increase in relative height, was negatively correlated with the relative height at the start of treatment and with the maximum pretreatment plasma GH response to insulin hypoglycaemia. There was no correlation with pretreatment relative height velocity or aetiology of GH deficiency. Height velocity improved in five of 14 children treated with thyroxine after starting GH. Discontinuation of GH for one year in 34 children resulted in a highly significant reduction in growth rate from 7.5 (2.4) cm/yr to 2.5 (2.0) cm/yr, however four prepubertal children continued to grow at a rate exceeding 4 cm/yr.

Age Determination by Skeleton↗
PubMed1989

ACTH deficiency: problems in recognition and diagnosis.

Corticotrophin (ACTH) deficiency is an important cause of a potentially lethal form of adrenocortical failure. Difficulties can arise in making the diagnosis, especially when secretion of other pituitary trophic hormones is normal. Presenting features of seven patients with ACTH deficiency, in whom the diagnosis was difficult for a variety of reasons, are reported and discussed. Two patients had a normal cortisol response to synthetic ACTH. The possibility of ACTH deficiency should be considered in any patient presenting with weight loss, vomiting, muscular fatigue and stiffness, hyponatraemia or hypoglycaemia.

Adolescent↗
PubMed1989

Effects of alpha-2 adrenoreceptor blockade by yohimbine on the hormonal response to hypoglycaemic stress in normal man.

In order to evaluate the effect of alpha-2 adrenoreceptor blockade on the ACTH response to insulin-induced hypoglycaemia, six normal men were studied with and without yohimbine (30 mg p.o.) premedication. Despite a similar hypoglycaemic stimulus and significant suppression of the growth hormone response (P less than 0.05), no change was observed in basal or stimulated plasma ACTH, cortisol, arginine vasopressin (AVP) or prolactin responses following yohimbine. We conclude that alpha-2 adrenoceptor blockade with yohimbine does not significantly affect the ACTH response to hypoglycaemia in man.

Adrenocorticotropic Hormone↗
PubMed1989

Effect of an osmotic stimulus on the secretion of arginine vasopressin and adrenocorticotropin in the horse.

Arginine vasopressin (AVP) is released in response to changes in blood osmolality and is also a putative secretagogue for ACTH. However, it is unclear whether osmotically generated increases in AVP in the physiological range influence ACTH secretion. We have studied this question using our unique noninvasive technique for collecting pituitary venous blood in six normal conscious horses that received an iv infusion of hypertonic saline (HS; 5%, 0.07 ml/kg.min) for 45-60 min. Pituitary and jugular venous samples were collected every 5 min for 40 min before, during, and for 20 min after HS. During HS, mean blood osmolality rose (P less than 0.01), with a mean peak increase of 14.8 mosmol/kg (range, +6-+37 mosmol/kg). Jugular AVP rose (P less than 0.01) from 0.56 +/- 0.18 pmol/liter (mean +/- SEM) before HS to 2.16 +/- 0.86 pmol/liter during HS. Mean jugular AVP and osmolality were correlated (r = 0.82; P less than 0.05) during HS. Mean jugular ACTH concentrations increased (P less than 0.01) from 49 +/- 9 ng/liter before HS to 148 +/- 54 ng/liter during HS, while mean cortisol levels during and after HS exceeded basal levels (P less than 0.05). Pituitary AVP and ACTH concentrations exceeded jugular concentrations by up to 100-fold, and mean (P less than 0.01 for both) and peak (P less than 0.001 for both) levels increased during HS. AVP and ACTH secretion during HS were pulsatile. The mean and peak changes in pituitary AVP were significantly correlated with those in ACTH. For the six horses together, pituitary ACTH and AVP concentration changes occurred synchronously during the experiment (P less than 0.001), and the paired AVP and ACTH concentrations were highly correlated (r = 0.73; n = 129 pairs; P less than 0.001). We conclude that 1) physiological changes in AVP secretion are closely associated with comparable changes in ACTH secretion, and 2) osmotic signals that presumably activate the magnocellular neurons of the supraoptic and paraventricular nuclei may be physiologically relevant regulators of corticotrope function.

Adrenocorticotropic Hormone↗
PubMed1988

Plasma 11-deoxycortisol and cortisol following dexamethasone in psychiatric patients.

As it has been suggested that calculating the ratio of cortisol to its biosynthetic precursor, 11-deoxycortisol, may enhance the sensitivity of the dexamethasone suppression test (DST) for depression, cortisol and 11-deoxycortisol were measured in 90 subjects undergoing this test. Among these subjects, post-dexamethasone cortisol and 11-deoxycortisol levels were significantly correlated (r = 0.65, P less than 0.001) and evaluating the ratio of cortisol to 11-deoxycortisol decreased rather than enhanced sensitivity of the DST.

17-Hydroxycorticosteroids↗
PubMed1988

The effects of cortisol, vasopressin (AVP), and corticotropin-releasing factor administration on pulsatile adrenocorticotropin, alpha-melanocyte-stimulating hormone, and AVP secretion in the pituitary venous effluent of the horse.

Plasma ACTH, arginine vasopressin (AVP), and alpha MSH were measured in pituitary venous effluent at 5-min intervals from five unanesthetized horses during cortisol infusion and after an iv bolus of AVP or ovine (o) CRF. In control experiments (no hormone) there was a significant overall correlation between the timing of concentration changes in ACTH and alpha MSH. Cortisol infusion increased jugular cortisol levels by 70% and was associated with a reduction in mean ACTH, AVP, and alpha MSH secretion rates and ACTH peak secretion rate, but did not alter the observed pulse frequencies of these hormones. Administration of AVP raised plasma concentrations to a level comparable to the spontaneous peaks in pituitary venous blood and resulted in an increase in the secretion of ACTH and alpha MSH in all horses. Furthermore, spontaneous AVP peaks occurred in pituitary venous blood between 90 and 180 min after AVP injection, indicating that the exogenous hormone did not suppress AVP secretion. oCRF administration led to a prolonged elevation in plasma CRF and an increase in secretion of ACTH and alpha MSH, but not AVP, in all horses. The pulsatile secretion of ACTH and alpha MSH was maintained despite plasma CRF levels in excess of 400 pmol/liter, and the timing of concentration changes in AVP and ACTH continued to be highly correlated. It is concluded that pulsatile ACTH secretion continues during cortisol, oCRF, or AVP administration. Like that of ACTH, alpha MSH secretion is stimulated by oCRF and AVP administration and suppressed by cortisol. Although the timing of concentration changes in ACTH and alpha MSH is highly correlated, the correlation of the actual concentrations of these two hormones varies considerably in different animals.

Adrenocorticotropic Hormone↗
PubMed1988

Effect of isolation stress on concentrations of arginine vasopressin, alpha-melanocyte-stimulating hormone and ACTH in the pituitary venous effluent of the normal horse.

A non-surgical, non-stressful technique was used for collection of pituitary venous blood from five conscious horses every minute for two 10-min periods before and during isolation from the herd, which caused a predictable, yet humane and physiological, emotional stress. Pituitary blood was also sampled every 5 min for two approximately 90-min periods before and after isolation, while jugular blood was sampled every 15 min throughout the experiment. During isolation, all horses became agitated, hyperventilating and sweating. Packed red cell volume increased, as did pituitary venous concentrations of adrenaline (mean +/- S.E.M. concentration before isolation, 621.5 +/- 112.3 pmol/l; peak during isolation, 2665.4 +/- 869.8 pmol/l; P less than 0.05) and noradrenaline (before, 871.8 +/- 111.8 pmol/l; peak, 2726.1 +/- 547.4 pmol/l; P less than 0.02). Concentrations of arginine vasopressin (AVP) were higher in pituitary venous but not in jugular blood during isolation than during the preceding 10-min period (P less than 0.05). Although AVP secretion increased in all horses, in three of the five it rose dramatically in the first minute of isolation to 25.7 (horse 1), 13.6 (horse 4) and 145.1 (horse 5) times the level in the last sample collected before isolation. Mean pituitary venous concentrations of ACTH and alpha-MSH increased during isolation in the three horses which had large increases in AVP secretion, but, overall, stress did not significantly affect ACTH or alpha-MSH secretion. Similarly, mean jugular cortisol levels were not significantly altered by isolation. However, the magnitudes of ACTH, AVP and alpha-MSH responses to isolation were negatively correlated with the jugular cortisol level before isolation. The changes in pituitary venous concentrations of ACTH and AVP were synchronous under resting conditions, whether samples were collected at intervals of 1 (P less than 0.01) or 5 (P less than 0.005) min; however, this synchrony was lost during isolation. The changes in pituitary venous concentrations of ACTH and alpha-MSH were synchronous both at rest (P less than 0.025 for 1-min sampling, P less than 0.01 for 5-min sampling) and during isolation (P less than 0.01). We conclude that isolation stress increases AVP secretion and may alter the temporal relationship between pituitary venous concentrations of AVP and ACTH. Furthermore, the magnitude of the responses of AVP, ACTH and alpha-MSH to isolation is significantly affected by the prevailing cortisol level.

Adrenocorticotropic Hormone↗
PubMed1988

Circulating plasma corticotrophin-releasing factor-like immunoreactivity.

Normal human peripheral plasma, examined by direct radioimmunoassay (RIA) for human corticotrophin-releasing factor (CRF) using seven different antisera, showed marked inhibition of tracer binding to antiserum. This apparently high CRF-like immunoreactivity (CRF-LI) did not dilute in parallel with synthetic human CRF-41. In comparison, most equine and ovine plasma samples had low CRF-LI concentrations. Plasma fractionation of both normal and late pregnancy human plasma on Sephadex G-75 at neutral pH indicated the majority of the CRF-LI to be of large molecular size. The molecular weight was estimated to be approximately 29,000 following chromatography of normal human plasma on Sephacryl S-200. The high CRF-LI in normal plasma was reduced to barely detectable levels by methanol treatment despite the recovery of added human CRF-41 of greater than 80%. Methanol extracts of late pregnancy human plasma, however, retained high CRF-LI which exhibited the immunoreactive and Sephadex elution characteristics of synthetic human CRF-41. 125I-Labelled human CRF-41 added to human plasma showed a reversible, time-dependent alteration in molecular size and reduction in binding to excess antiserum. These findings indicate that direct RIA of human CRF in unextracted plasma leads to spurious results and suggest the presence in human plasma of an interfering factor and/or binding substance that is not generally apparent in equine or ovine plasma under the conditions described.

Animals↗
PubMed1988

Characteristics of the ACTH response to repeated pulses of corticotrophin-releasing factor and arginine vasopressin in vitro.

A multi-column perifusion system was used to investigate the dynamics of the dose-response relationships of ACTH release by ovine pituitary cells when stimulated by both corticotrophin-releasing hormone (CRF) and arginine vasopressin (AVP) given alone and in combination. A dose-response relationship was obtained when 10-min pulses were given at 60-min intervals over the range of 0.002-2000 nmol CRF/1 and 1-2000 nmol AVP/1, with a minimum effective concentration of 0.02 nmol CRF/1 or 1 nmol AVP/1. When AVP was given together with CRF, the expected potentiation of the ACTH response occurred when compared with the summed response of these secretagogues given separately. At the higher concentrations of CRF and AVP used, the ACTH responses to repeated pulses decreased with time during the experiment. The rate of this loss of responsiveness was significantly correlated to the size of the response to the first pulse (for CRF: r = 0.89, P less than 0.01; for AVP: r = 0.95, P less than 0.01), being greatest when the response was potentiated by adding the secretagogues together (for CRF plus AVP: r = 0.95, P less than 0.01). Reduced availability of receptors or changes in intracellular transduction processes may contribute to this desensitization. Reduced levels of secretable ACTH do not appear to be implicated because desensitization to pulses of one secretagogue did not cause equivalent desensitization to the other. In addition, cells stimulated continuously with submaximal levels of either secretagogue showed desensitization while more ACTH was still available for release to higher levels of stimulant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1987

The dexamethasone suppression test in psychiatry.

The dexamethasone suppression test (DST) for depression (melancholia) has been the focus of considerable recent interest because of claims that it may be a sensitive and specific biological marker for melancholia. When the data from four separate studies were combined, 52% of our patients with major depression were DST nonsuppressors. However, nonsuppression was also observed in 11% of manic patients, 20% of schizophrenic patients and 15% of nondepressed abstinent alcoholics. These results, in conjunction with other reports, suggest that the specificity of the test is not sufficiently high to make it a satisfactory general diagnostic test.

Alcoholism↗