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Biomedical subjects

R A Donald

Publications and source records attributed to R A Donald.

At least 127 records · Page 7Linked to original sources
PubMed1982

Patients presenting with Addison's disease need not be pigmented.

Three consecutive cases of Addison's disease without increased pigmentation are described. We suggest that the absence of this important physical sign contributed to serious delays in diagnosis and markedly increased morbidity. We emphasize that, despite the usual textbook description, excess pigmentation is not necessarily a feature of Addison's disease.

Addison Disease↗
PubMed1982

Metabolic clearance rate in sheep of a met-enkephalin analogue estimated by radioimmunoassay.

A sensitive and specific radioimmunoassay developed for measuring the met-enkephalin analogue d-ala2-met(0)5-ol-enkephalin (DAMME) was used to study the pharmacokinetics of DAMME in the circulation of sheep. Plasma concentrations of DAMME were measured at varying time-intervals after an intravenous bolus injection or following a constant intravenous infusion of the analogue. The mean metabolic clearance rate of DAMME was 2.8 ml/min per kg, the mean circulating half-life was 52 min and the mean volume of distribution was 190 ml/kg. The longer circulating time of the analogue when compared with that of naturally occurring met-enkephalin would appear to explain its prolonged analgesic effect.

Animals↗
PubMed1981

Lack of effect of hyperprolactinemia on glucose disposal and insulin secretion in patients with prolactinomas.

The role of prolactin as a diabetogenic hormone is still controversial. The present study examines intravenous glucose tolerance in six subjects with prolactin secretion pituitary adenomas. Testing was performed in each individual both in the untreated high prolactin state and again after prolactin was reduced by bromocriptine treatment for three months. Lowering serum prolactin failed to improve intravenous glucose tolerance or alter insulin release. It is concluded that prolactin has no significant effect on glucose disposal.

Adenoma↗
PubMed1981

Pituitary-ovarian function in normal women during the menopausal transition.

The excretion of follicle stimulating hormone (FSH), luteinizing hormone (LH), oestrogens and pregnanediol was measured in weekly urine samples collected for 14-87 weeks (median, 43 weeks) from thirty-one perimenopausal women aged 36-55 years (median, 50 years). The results were compared with those found in twenty-two postmenopausal women aged 55.4 +/- 5.4 years (mean +/- SD), and in twenty premenopausal women aged 44.4 +/- 3.4 years with regular, ovulatory, menstrual cycles. Women classed as perimenopausal had a recent history of irregular menstrual cycles following regular cyclicity. The hormone patterns observed in the perimenopausal women varied widely, both between individuals and from time to time in the same individual. They ranged from ovulatory cycles with low premenopausal levels of FSH, to transient episodes indistinguishable from those found in postmenopausal women with high levels of FSH and LH. Between these extremes were patterns rarely seen at other times in reproductive life: namely, (1) in fourteen women on thirty-two occasions lasting 2-9 weeks, postmenopausal levels of FSH and LH occurred in association with high oestrogen levels; (2) in eighteen women on thirty occasions lasting 2-8 weeks, there was an elevation of LH (but not FSH) into the postmenopausal range; (3) in thirteen women on twenty-six occasions lasting 1-2 weeks, there was an elevation of FSH (but not LH) into the postmenopausal range. These patterns were not seen in any of the premenopausal women. Typically, the approach of the menopause was marked by an increased incidence of high postmenopausal levels of FSH and LH. Ovulatory cycles were observed at all stages in the perimenopause, and occurred within 16 weeks of the last menstrual period in seven of the thirteen women who became postmenopausal during the study. It is concluded that the appearance of high levels of FSH and LH is characteristic of the perimenopause and often precedes the sustained loss of sex hormone secretion by the ageing ovary. Postmenopausal biochemical parameters are no guarantee of the postmenopausal state.

Adult↗
PubMed1981

The effects of different dose regimes of D-SER(TBU)6-LHRH-EA10 (HOE 766) in subjects with hypogonadotrophic hypogonadism.

Eight male patients with hypogonadotrophic hypogonadism were treated with injections of a long acting LHRH analogue, HOE 766. Six of the patients were on daily subcutaneous injections of 5 microgram of this analogue at the start of this study and were changed to alternate-daily injections of the same dose for 1-3 months. They were then treated with twice-daily injections of 0.5 microgram HOE 766, as was another subject not previously treated. The HOE 766 twice-daily was given alone for 1 or 2 months and then sex steroid replacement therapy was added to this for a further 4-5 months. There was no clinical improvement or rise in plasma testosterone levels until sex steroid therapy was commenced. Basal LH and FSH levels and peak responses to 100 microgram LHRH remained low throughout the study. It is concluded that these variations in dose and interval of administration do not overcome the lack of pituitary response which is a feature of prolonged treatment with LHRH analogues.

Adolescent↗
PubMed1980

1,25-dihydroxy-vitamin D3: a new treatment for hypoparathyroidism.

Eleven subjects aged four to 76 years with primary hypoparathyroidism have been treated with 1,25-dihydroxycholecalciferol (1,25-D3). Five subjects were not on vitamin D analogues before starting this drug. 1,25-D3 was found to be an effective treatment and a rapid biochemical response to dose adjustments was observed. In two subjects hypercalcaemia and reversible renal failure occurred. Thiazide-type diuretics necessitated dose reductions in a further two subjects. A scheme for starting hypoparathyroid subjects on this treatment is suggested. The need for regular biochemical assessment and awareness of possible drug interactions is emphasised. It is felt that 1,25-vitamin D3 has practical advantages over traditional forms of vitamin D in the treatment of hypoparathyroidism.

Adult↗
PubMed1980

Effect of time, temperature and freezing on the stability of immunoreactive LH, FSH, TSH, growth hormone, prolactin and insulin in plasma.

1. Endogenous LH, FSH, TSH, growth hormone, prolactin and insulin were measured by radioimmunoassay in human plasma samples stored at 4 degrees, 20 degrees and 37 degrees for up to 8 days or repeatedly frozen and thawed. 2. At 4 degrees, the concentrations of all hormones were stable for at least 8 days; at 20 degrees only LH, FSH and TSH were stable for 8 days; at 37 degrees only TSH was stable for 8 days. 3. All the hormones except insulin were stable during 5 freeze-thaw cycles.

Drug Stability↗
PubMed1980

Concentrations and kinetics of carbamazepine in whole saliva, parotid saliva, serum ultrafiltrate, and serum.

Six healthy subjects received a 400-mg oral dose of carbamazepine (CBZ). CBZ concentrations were determined by enzyme immunoassay in whole saliva, serum, and serum ultrafiltrate over 82 hr. After 30 hr the log concentration-time plots declined linearly with similar elimination half-lifes in all three fluids. Although the mean ultrafiltrate curve was lower than the mean salivary curve, the area under the curve, volume of distribution, and total body clearance calculated from whole saliva and ultrafiltrate data were not different. The mean CBZ concentration ratios of whole saliva/total serum and ultrafiltrate/total serum of the individual subjects ranged from 19.6% to 34.7% and from 19.0% to 28.8%. Linear correlations were found between salivary CBZ concentrations and serum (r = 0.872, p < 0.001) and ultrafiltrate concentrations (r = 0.916, p < 0.001). Whole salivary and uncontaminated parotid salivary CBZ concentrations were not different and were independent of volume of fluid produced, pH of saliva, and degree of stimulation. These results indicate that whole saliva may be a suitable medium for monitoring free concentrations of CBZ and may provide a noninvasive alternative to blood.

Adult↗
PubMed1980

Evaluation of the three hour metyrapone test in adults.

The prolonged metyrapone test is used to assess the hypothalamic-pituitary-adrenal axis. The dynamic responses of cortisol, ACTH and 11-deoxycortisol over the 3 h of the single morning dose metyrapone test have been examined in fourteen normal adult subjects. In every case there was a rapid, sustained fall in cortisol, but the resultant ACTH responses were extremely variable and in two subjects did not exceed values obtained during the control studies. The rise in 11-deoxycortisol was also variable and in several instances occurred without any significant elevation in ACTH. In these cases, the rise in 11-deoxycortisol may be due to a normal level of production of steroids with a shift from cortisol to 1-deoxycortisol induced by the metyrapone. Thus, the hypothalamic-pituitary-adrenal axis may not be adequately tested, and this together with the high incidence of unpleasant side effects, makes the 3 h oral metyrapone test unsatisfactory for routine use in adults.

Adrenocorticotropic Hormone↗
PubMed1980

Aldosterone regulation in primary aldosteronism: influence of salt balance, posture and ACTH.

The response of aldosterone to manipulations of the renin-angiotensin and hypothalamic-pituitary-adrenal systems has been studied in thirteen patients with primary aldosteronism due to a single adenoma (ten patients) or bilateral hyperplasia (three patients). The aldosterone response to dietary sodium restriction was small and variable, although urinary aldosterone excretion increased in nine out of twelve studies. The response of patients with hyperplasia could not be distinguished from those with adenoma. All patients were unresponsive to salt loading. By contrast, plasma aldosterone fell in all patients after overnight dexamethasone (1 mg) and increased after brief (1 h) physiological ACTH stimulation. During prolonged erect posture, plasma aldosterone increased in the three patients with hyperplasia and decreased or remained unchanged in patients with ademona. Changes in plasma renin activity were similar in both groups. These studies show that patients with primary aldosteronism, while largely unresponsive to manipulations of sodium balance, retain sensitivity to small and acute changes in ACTH. The different behaviour of patients with hyperplasia to prolonged erect posture cannot be explained by insensitivity to ACTH, but could be due to a relative increase in sensitivity to angiotensin.

Adenoma↗
PubMed1980

Functional significance of idiopathic adrenal calcification in the adult.

Two young adults with idiopathic adrenal calcification are described. In one patient the calcification was probably secondary to adrenal haemorrhage in the neonatal period. Neither patient exhibited clinical features suggestive of adrenal cortical insufficiency, and baseline serum cortisol levels were normal. The corticosteroid responses to ACTH administration and to other provocative tests indicated that both glucocorticoid and mineralocorticoid reserve was normal. One patient showed an appropriate epinephrine response to insulin-induced hypoglycaemia. We conclude that even extensive adrenal calcification may be compatible with completely normal adrenal function. Since, however, little is known of the natural history of this condition, lifelong follow-up of such patients is advised.

Adrenal Cortex Function Tests↗
PubMed1980

Pituitary function in normoprolactinaemic infertile men receiving bromocriptine.

A double blind trial of bromocriptine 7.5 mg daily versus placebo was carried out in ten infertile men. Pretreatment basal plasma prolactin, thyroid stimulating hormone (TSH) testosterone and luteinizing hormone (LH) concentrations were normal, but plasma follicle-stimulating-hormone (FSH) was raised in four individuals. After 4 months treatment with bromocriptine a significant fall in plasma prolactin was observed (P less than 0.01), both under basal conditions and following thyroid stimulating hormone releasing hormone (TRH). Basal plasma gonadotrophin, testosterone and thyroid stimulating hormone (TSH) concentrations did not alter. No change in sperm density, volume or motility was noted. However an apparent fall in the peak plasma LH (but not FSH) response to gonadotrophin releasing hormone (LHRH) was observed in patients receiving bromocriptine. This reduction in plasma LH responsiveness was significant when compared with the baseline response (P less than 0.05) but failed to reach significance when compared with the placebo response. It is concluded that prolonged bromocriptine therapy in normoprolactinaemic men does not suppress FSH secretion, and any reduction in plasma LH responsiveness to LHRH is not accompanied by a significant fall in plasma testosterone.

Adult↗
PubMed1980

Free insulin, C-peptide and glucagon profiles in insulin dependent diabetes mellitus.

Glucose and hormone profiles, including plasma levels of glucagon, GH, total insulin, free immunoreactive and biologically active insulin were determined by hourly sampling in two groups of insulin dependent diabetics. The five patients in Group I were recently diagnosed and still had residual beta-cell function. The other six in Group II had disease of longer duration, had developed insulin antibodies, and were non-secretors of C-peptide. All patients were studied while receiving their usual maintenance doses of Semilente monocomponent insulin (Novo). Daily insulin requirements were 25.6 +/- 4 U in Group I and 52.2 +/- 7 U in Group II. The glucose profiles were similar in the periprandial periods but over the whole 24-hour period control was more unstable in the patients of Group II and during the period 2400-0200 h plasma glucose fell to low levels (minimum plasma glucose 1.5-3.0 mmol/l). Free insulin levels rose to peak levels over a similar time course but then fell more slowly in the Group II subjects. These patients had higher free, biologically active insulin and lower glucagon levels which were coincident in time with the early morning hypoglycaemia. These observations suggest that raised free insulin levels in the setting of an impaired counter-regulatory glucagon response are one of the factors contributing to glucose instability in long-standing diabetics.

Adolescent↗