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Biomedical subjects

R A Donald

Publications and source records attributed to R A Donald.

At least 109 records · Page 6Linked to original sources
PubMed1984

Suppression and stimulation of growth hormone release in sheep by somatostatin analogs.

The inhibitory and stimulatory effects of somatostatin analogues on growth hormone secretion have been studied in the sheep. Plasma immunoreactive growth hormone (GH) was stimulated by the iv administration of the antilipolytic compound 3,5-dimethylpyrazole and was followed by infusion of somatostatin (SRIF) and analogues into the carotid artery. The analogues D-trp8-D-cys14-SRIF, des-AA1,2,4,5,12D-trp8-D-cys-14SRIF, and SRIF-Wy 40793 were shown to cause a dose-dependent suppression of plasma GH, followed by a significant rise ("rebound") on terminating the infusion. In general, the greater the suppression, the greater the rebound. A significant correlation between the rebound increase in plasma GH and dose of both SRIF and des-AA1,2,4,5,12D-trp8-cys14-SRIF was demonstrated (p less than 0.01 and p less than 0.001, respectively). This analogue and Wy-40793 showed a significantly greater rebound than did SRIF following 50% suppression of the GH response (p less than 0.01 and p less than 0.05, respectively). Although two analogues were shown to be significantly more potent than SRIF (p less than 0.01), in this sheep bioassay the duration of action did not appear to be longer than that of the native hormone for any of the three analogues.

Animals↗
PubMed1984

Effect of metoclopramide on aldosterone and regulatory factors in man.

To determine the role of known secretagogues in the aldosterone response to dopamine blocking agents, plasma levels of ACTH, angiotensin II, potassium and plasma catecholamines were measured in five normal male subjects before and after intravenous injection of saline or 10 mg metoclopramide. There were no consistent changes in hormone levels after saline injection. After metoclopramide, plasma aldosterone increased three-fold to peak values at 20 min post-injection. A significant increase in aldosterone was observed within 10 min during which period there was no significant change in plasma ACTH, plasma renin activity AII or K. Plasma levels of cortisol, noradrenaline, adrenaline and dopamine showed no significant changes after injection of metoclopramide which induced a ten-fold rise in plasma prolactin. These results provide direct evidence that factors other than the plasma concentration of ACTH, AII and K--or fluctuations in plasma catecholamines--are likely to be responsible for the acute increase in plasma aldosterone after metoclopramide injection in normal man.

Adrenal Cortex↗
PubMed1984

Reduced fertility in women with X chromosome abnormality.

One patient with the karyotype 46,X,del(X)(p11.23) and three patients with 45,X/46,XX mosaicism were fertile or showed normal ovarian function. The patient with the Xp deletion has two daughters with the same chromosomal abnormality. A study of these patients and of others reported in the literature indicated that fertility of patients with X chromosomal abnormality has a markedly shorter duration than fertility of the normal female. Menopause commonly occurred during the second and third decade of age. We suggest that such fertility is related to the rate of germ cell attrition and hypothesize that germ cell attrition in the human female is influenced by genes of multiple effect which are carried on the X chromosome. The more of these genes which are present the slower the rate of germ cell attrition.

Adolescent↗
PubMed1984

The effect of ovine corticotropin-releasing factor on catecholamine, vasopressin, and aldosterone secretion in normal man.

The 41-residue ovine corticotropin-releasing factor (CRF) was administered iv to five normal men. A significant rise in plasma corticotropin (ACTH), cortisol, and aldosterone was demonstrated after a dose of 200 micrograms. There was no demonstrable change in supine blood pressure, pulse rate, plasma vasopressin, renin, catecholamines, insulin, glucagon, or glucose. It is concluded that 200 micrograms ovine CRF stimulates ACTH and cortisol secretion independently of any change in peripheral plasma levels of vasopressin and catecholamines. The cortisol and ACTH responses to ovine CRF were less marked but more prolonged than those after insulin-induced hypoglycemia. The relatively small increment in plasma ACTH, which was well within the physiological range, was associated with a significant increase in plasma aldosterone. Posterior pituitary function was not affected by this dose of ovine CRF.

Adrenocorticotropic Hormone↗
PubMed1983

Amenorrhoea.

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Adolescent↗
PubMed1983

Effects of an enkephalin analogue (DAMME) on pituitary and pancreatic function in sheep.

The hormonal secretory effects of intravenously and intracerebroventricularly administered DAMME have been studied in the sheep. Serum prolactin and growth hormone levels were significantly elevated after i.v. injection of DAMME (14 micrograms kg-1) while a significant and considerably more prolonged increase occurred following i.c.v. administration of 20 micrograms of the analogue. The responses to i.c.v. but not to i.v. injected DAMME were attenuated by prior i.v. injection of naloxone. Administration of DAMME i.c.v. resulted in a detectable concentration in the peripheral circulation within two minutes and maximal levels at 120-150 minutes. No significant changes occurred in circulating concentrations of the pancreatic hormones investigated although there was a trend to somatostatin and pancreatic polypeptide levels being elevated after systemic injection of the analogue.

Animals↗
PubMed1983

Hormonal effects and metabolic clearance rate of the enkephalin analogue DAMME in man.

The enkephalin analogue DAMME (0.25 mg) and normal saline were administered by slow intravenous injection to six normal male subjects in a double-blind crossover study. Plasma DAMME concentrations were measured by a specific radioimmunoassay. A significant rise in plasma growth hormone and prolactin and a significant fall in plasma corticotrophin and cortisol concentrations were observed. The fall in pancreatic polypeptide concentration just failed to reach significance. No significant changes were observed in insulin, glucagon, glucose, adrenaline and noradrenaline. Serum concentrations of DAMME were initially high (greater than 6.7 nmol/1) corresponding with the observed maximum plasma growth hormone and prolactin responses. The serum DAMME concentration was readily detectable when plasma growth hormone and prolactin had returned to control levels, but corticotrophin and cortisol were still significantly depressed.

Adrenocorticotropic Hormone↗
PubMed1983

Skin thickness in patients with acromegaly and Cushing's syndrome and response to treatment.

Radiological assessment of skin thickness (ST) was assessed in 22 patients with acromegaly and 17 patients with Cushing's syndrome. The age ranges of the patients studied and the 55 individuals in the control group were comparable. The skin thickness in males was significantly greater than in females (P less than 0.01). Mean skin thickness in patients with acromegaly and Cushing's syndrome was significantly greater and less respectively than the mean skin thickness of the normal controls (P less than 0.02). Following successful treatment of acromegaly (growth hormone less than 5 micrograms/l) there was a significant reduction in skin thickness (P less than 0.02 males: P less than 0.01 females). The skin thickness declined at approximately 0.3 mm/year for the first two years and more slowly thereafter. A highly significant correlation was observed between the logarithm of the pre and post treatment plasma GH concentrations and ST values. With one exception, all patients with growth hormone (GH) levels greater than 5 micrograms/l had ST values above the normal range. At an average of 4.5 years after successful treatment of Cushing's syndrome the average increase in ST was 0.23 mm (P less than 0.01). It is concluded that the measurement of skin thickness is a useful screening test for both acromegaly and Cushing's syndrome and provides an objective assessment of the clinical response to treatment.

Acromegaly↗
PubMed1983

Hypogonadotrophic hypogonadism resistant to hCG and responsive to LHRH: report of a case.

The treatment of hypogonadotrophic hypogonadism with gonadotrophin releasing hormone (LHRH) has proved difficult in the past because of a progressive decline in the pituitary gonadotrophin response. These early studies generally used large relatively infrequent doses of natural LHRH (Davies et al., 1977) or analogues with a prolonged action (Smith et al., 1979). Recently, several reports have indicated that the lack of gonadotrophin response to LHRH can be overcome by frequent administration of low doses of natural LHRH in a pulsatile fashion (Belchetz et al., 1978; Crowley et al., 1980; Jacobson et al., 1979; Schoemaker et al., 1981; Valk et al., 1980). However, it is not known whether those patients with hypogonadotrophic hypogonadism who fail to respond to human chorionic gonadotrophin (hCG) (Bardin et al., 1969) are capable of responding to LHRH. In this case report of a patient with hypogonadotrophic hypogonadism who was resistant to prolonged hCG therapy, normal pituitary gonadotrophin and testosterone responses were obtained following pulsatile LHRH administration. The sperm count rose to 11 X 10(6)/ml. His wife became pregnant and was delivered of a normal healthy female infant after an uneventful pregnancy.

Adult↗
PubMed1983

Comparison of preoperative and postoperative ACTH concentrations after bilateral adrenalectomy in Cushing's disease.

Up to one-third of subjects who have had bilateral adrenalectomy for treatment of Cushing's disease will develop Nelson's syndrome. To examine the value of pre-operative ACTH assays in predicting outcome, we have studied fifteen cases of Cushing's disease treated by bilateral adrenalectomy and pituitary irradiation. Three patients developed Nelson's syndrome. There was no significant correlation between preoperative ACTH level, either 8 am 'basal' or during metyrapone testing, and ACTH concentration post-treatment. Plasma ACTH concentration in the first year after treatment, however, showed a highly significant correlation with the latest postoperative value (n = 14, r = 0.684, P less than 0.01), even more marked when subjects with duration of follow-up less than 3 years were excluded (n = 11, r = 0.836, P less than 0.002). In nine of fifteen patients, plasma ACTH showed either no change or a definite fall during subsequent follow-up. We conclude that plasma ACTH measurement in the first post-operative year is a good indicator of eventual outcome. The continued fall in plasma ACTH shown in many patients after the first year of treatment suggests an effect of irradiation on the pituitary.

Adolescent↗
PubMed1983

The hormonal actions of corticotropin-releasing factor in sheep: effect of intravenous and intracerebroventricular injection.

The 41-residue ovine corticotropin releasing factor (CRF) was administered iv and intracerebroventricularly (icv) to merino sheep. A significant rise in plasma ACTH, beta-lipotropin (beta LPH) and cortisol was demonstrated after the administration of 200 micrograms, iv. A highly significant correlation between the increments in plasma ACTH and beta LPH was observed. The plasma ACTH rise was evident within 5 min and was abolished by the prior administration of 0.4-4.0 mg dexamethasone. No significant rise in plasma GH, LH, PRL, insulin, glucagon, pancreatic polypeptide, met-enkephalin, angiotensin II, aldosterone, or vasopressin could be demonstrated. Although smaller doses of CRF (50 ng to 5 micrograms) were effective when given icv, the ACTH response was more delayed. It is concluded that CRF stimulates a rapid increase in the secretion of ACTH and beta LPH in sheep. Suppression of this response by dexamethasone indicates that glucocorticoids are capable of acting on the pituitary to inhibit the ACTH response to CRF. The delayed response when CRF is given icv may be due to diffusion. The action of CRF appears to be relatively specific, in that the plasma concentrations of the other pancreatic, pituitary, and adrenal hormones measured were not affected.

Adrenal Cortex Hormones↗
PubMed1983

Glycerol prevents loss of immunoreactive follicle-stimulating hormone and luteinizing hormone from frozen urine.

First morning urine samples were collected from both menstruant and post-menopausal women and stored at -25 degrees C. Immunoreactive FSH disappeared from these samples (t1/2 = 30 days), ultimately stabilizing at about 20% of the initial value. The loss was more rapid at -20 degrees C and less rapid at -55 degrees C and +4 degrees C. Immunoreactive LH was also lost from frozen urine, but more slowly than FSH. The addition of glycerol to urine (0.52 mol/l) stored at -25 degrees C prevented loss of immunoreactive FSH and LH for at least 105 days.

Drug Stability↗
PubMed1982

Pituitary-ovarian function before, during and after the menopause: a longitudinal study.

The excretion of FSH, LH, oestrogens and pregnanediol was monitored once weekly in urine samples collected from eight peri-menopausal women aged 44-55 years (median, 52 years). Observations were commenced between 5 and 15 weeks before the menopause and were continued for 22-30 weeks after final menstruation. Amenorrhoea of greater than 2 years duration in association with a persistent elevation in gonadotrophin output was considered proof of the post-menopausal state. No clear hormonal change occurred at the time of the menopause. During the peri-menopause there is a transition from the regular ovulatory cycles of pre-menopausal women to the unvarying high gonadotrophin and low oestrogen excretion which is generally regarded as being characteristic of post-menopausal women. In the group studied, post-menopausal levels of FSH and LH were common before and episodes of high oestrogen excretion were not uncommon after final menstruation. Menstrual failure appeared to occur spontaneously at some stage during the transition from the pre- to the post-menopausal state, and not to be associated with its conclusion. From the hormonal point of view the immediately post-menopausal period could not be distinguished from the long cycles of peri-menopausal women. This suggests that an endometrial rather than a hormonal event might determine the time at which menstruation stops during the menopausal transition.

Adult↗
PubMed1982

Residual pancreatic function in insulin dependent diabetics.

The relative contributions of alpha and residual beta cell function and the presence of insulin binding antibodies to indices of glucose control have been assessed in a group of 44 patients with insulin dependent disease of variable duration. Residual beta cell secretion was detected in 18 patients (40%) but no patient receiving insulin for more than five years showed evidence of residual function. Indices of glucose control were significantly better (p less than 0.001) in patients demonstrating residual secretion. In contrast, no relation was found between glucose control and either fasting of post prandial plasma glucagon concentrations. Insulin binding antibodies were detected in all but two patients but did not correlate with either daily insulin dose or glucose control. These results are consistent with the view that residual beta cell function contributes to improved glucose control in the yearly years of insulin dependency but alpha cell function and insulin antibodies do not.

Adolescent↗