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Biomedical subjects

C R Edwards

Publications and source records attributed to C R Edwards.

At least 199 records · Page 11Linked to original sources

In vivo and in vitro studies on the effect of metoclopramide on aldosterone secretion.

Metoclopramide, a dopamine antagonist drug, elevated plasma aldosterone and prolactin levels without significantly affecting plasma renin activity, ACTH or potassium. Studies with isolated perfused rat zona glomerulosa cells showed that metoclopramide could directly stimulate aldosterone release and that this action was blocked by dopamine. These results suggest that dopamine may play an important inhibitory role in the control of aldosterone secretion.

Adrenal Glands↗

The effect of cyproterone acetate on serum testosterone, LH, FSH, and prolactin in male sexual offenders.

The anti-androgen, cyproterone acetate, was administered in a dose of 100 mg/day to eight adult male sexual offenders for 21-31 days. Serum testosterone fell to subnormal levels within 7 days and remained low for 6-28 days after treatment was stopped. The fall in testosterone was accompanied by a fall in serum luteinizing hormone (LH) and follicle stimulating hormone (FSH), and a rise in serum prolactin. All subjects experienced a decrease in libido and in frequency of masturbation. The probable mechanisms of action of cyproterone acetate are discussed, as is its potential role in the management of sexual offenders. These studies suggest that measurement of serum testosterone could be used as an index of compliance in sexual offenders treated with cyproterone acetate who are released on parole.

Adult↗

Endocrine function in the Prader-Willi syndrome.

Hypothalamic, pituitary and gonadal function was studied in five male and three female patients with the Prader-Willi syndrome. All were clinically hypogonadal: all males had low circulating testosterone levels, although in two females basal plasma oestradiol was within the normal range for the early follicular phase of the menstrual cycle. Basal gonadotrophin levels were low and the response to the intravenous ater 10 days and 6 weeks treatment with oral clomiphene (200 mg daily) was followed by a normal rise in luteinizing hormone (LH) and follicle stimulating hormone (FSH) in four out of five patients tested. All five males were tested with human chorionic gonadotrophin (hCG) and the rise in plasma testosterone was subnormonal in four. Treatment with hCG was continued for 6 weeks in these four patients, but in only one did testosterone levels rise (transiently) to the normal adult male range. In one female patient studied no rise in plasma oestradiol was detected in response to human menopausal gonadotrophin (hMG). These results suggest that the hypogonadism in the Prader-Willi syndrome is due to combined hypothalamic and primary gonadal abnormalities.

Adolescent↗

Pregnancy in patients presenting with hyperprolactinaemia.

Ninety-two pregnancies occurred in 76 hyperprolactinaemic patients treated with bromocriptine. Half conceived within three months of attempted conception. There was no evidence of an increased rate of spontaneous abortion, fetal abnormality, or multiple pregnancy; the three twin pregnancies occurred in women who were additionally treated with clomiphene and human chorionic gonadotrophin. Thirty-one patients had radiological evidence of a pituitary tumour; 14 with major radiograph changes in the pituitary fossa or serum prolactin concentrations greater than 100 ng/ml received pituitary irradiation before conception. None of the latter showed evidence of enlargement of the tumour during pregnancy. In contrast two of the four patients with similar tumours but who were not irradiated developed visual field defects, one with gross destruction of the pituitary fossa. Prophylactic treatment to limit subsequent tumour expansion during pregnancy in patients with prolactinomas is indicated, and pituitary irradiation before conception appears to be a safe and effective method to achieve this goal.

Bromocriptine↗

Cyclical combination chemotherapy and gonadal function. Retrospective study in males.

The effect of cyclical chemotherapy on fertility and gonadal function was investigated in seventy-four male patients who had been treated for advanced Hodgkin's disease. All patients were azoospermic after therapy, and, with a median follow-up period of 27 months (range 1--62 months), only four patients have regained spermatogenesis. Testicular biopsy showed an absence of germinal epithelium without other gross architectural changes. Despite this high degree of infertility, 60% of patients were practising contraception. A decline in libido and sexual performance with frequent long periods of sexual inactivity was noted by most men during therapy. Although some recovery was apparent once therapy was stopped, this was incomplete in approximately half of the patients. Follicle-stimulating-hormone levels were consistently raised after therapy at all periods of study. Median luteinising-hormone levels were at, or just above, the upper limit of normal, and median testosterone levels were normal. Increased prolactin levels were noted in 42% of patients, of whom about a half had an identifiable cause for hyperprolactinaemia. Return of spermatogenesis could not be predicted by serial hormone assessment. Because of the guaranteed infertility and the low frequency and unpredictability of recovery of spermatogenesis, sperm storage should be available for male patients undergoing cytotoxic therapy, since most of these patients may enjoy prolonged survival. Hormone-replacement therapy will usually be unnecessary. However, the probability of major changes in libido and sexual performance should be discussed with patients so that additional stress can be avoided. Contraceptive advice should be available to those who require it.

Adolescent↗

Relation of plasma aldosterone concentration to diuretic treatment in patients with severe heart disease.

To assess the relation of hyperaldosteronism and potassium depletion to the intensity of diuretic therapy we have measured plasma aldosterone by radioimmunoassay and total exchangeable potassium by radioisotope dilution in 24 patients when they were stable at the end of their preparation for cardiac operation. Some patients required intensive frusemide therapy to reach an optimal state for operation and many showed hyperaldosteronism. Plasma aldosterone was significantly related to daily dose of frusemide (r=0.77). Depletion of total exchangeable potassium expressed in terms of predicted weight was significantly related to plasma aldosterone (r= -0.64). The reduction in total exchangeable potassium is interpreted as chiefly related to loss of lean tissue mass from the wasting that leads to cardiac cachexia, but evidence is presented on the basis of measurements of extracellular fluid volume as sulphate space (20 patients) of entry of sodium into the cells which may indicate a true cellular potassium loss. Although plasma potassium is usually easily maintained with oral potassium supplements or aldosterone antagonists, we postulate that intensive diuretic therapy in severe heart disease may provoke hyperaldosteronism which accentuates potassium loss and may contribute to wasting and to intracellular potassium depletion in critical tissue, such as myocardium.

Adult↗

Evaluation and application of magnetizable charcoal for separation in radioimmunoassays.

We compared conventional charcoal separation of antibody-bound and free antigen with a novel method involving magnetizable particles containing charcoal. The magnetizable charcoal separation method was as effective as the conventional method for a wide range of radioimmunoassays, including those for several steroids and small polypeptide hormones. In a detailed comparison of conventional vs. magnetizable charcoal for radioimmunoassay of aldosterone, the magnetizable charcoal had several advantages: it did not require prior coating with dextran or protein, varied less with time and temperature, required no centrifugation, and took less time for separation. The correlation of results obtained with magnetizable and conventional charcoal separation was excellent (n = 89, r = 0.98, p less than 0.001), and the coefficient of variation for the separation with magnetizable charcoal was 0.5%.

Aldosterone↗

Psychiatric manifestations of Cushing's syndrome: response to lowering of plasma cortisol.

The incidence of psychiatric abnormalities has been assessed in 38 patients with Cushing's syndrome and two with alcohol-induced pseudo-Cushing's syndrome. Twenty-six patients were examined by one of us using a standardized psychiatric interview, and this group included all those with severe to moderate psychiatric disorders. Depression was the commonest symptom: five patients (13%) were markedly or severely depressed, four (10%) were moderately depressed and 13 (32%) were mildly depressed. Four patients exhibited other, non-depressive psychiatric symptoms and only 14 (35%) were judged free from psychiatric abnormality. The first line of treatment was to reduce the circulating cortisol level either by adrenalectomy or by treatment with oral metyrapone; both patients with alcohol-induced pseudo-Cushing's syndrome were treated by alcohol withdrawal. Once the plasma cortisol level was successfully controlled, depressive symptoms were relieved in all five patients with marked or severe depression and in three of the four who were moderately depressed. Mild depressive symptoms were relieved in six of the 13 affected. It is concluded that metyrapone may be of considerable value in the management of the acute psychiatric states which may occur in Cushing's syndrome and these findings are discussed in the light of their possible pathogenesis.

Adolescent↗

Hormonal and metabolic responses to an enkephalin analogue in normal man.

An enkephalin analogue [D-Ala2, MePhe4, Met(o)-ol] enkephalin (DAMME), given intravenously to normal subjects raised serum prolactin and growth-hormone levels but lowered serum levels of luteinising hormone, follicle-stimulating hormone, cortisol, and corticotrophin. There was also a small fall in total glucagon and gastric inhibitory peptide (G.I.P.) and a rise in thyrotrophin. beta-Lipotrophin, motilin, vasoactive intestinal peptide, insulin, gastrin, and pancreatic glucagon were unchanged. Blood-glycerol increased, and blood lactate, alanine, and glucose fell. Prior administration of the opiate antagonist, naloxone, attenuated the hormonal responses to DAMME. This enkephalin analogue produces endocrine and metabolic changes in man which may be mediated through opiate-binding receptors both within and outside the brain. The enkephalins and related substances may provide an important link between perception, behaviour, and neuroendocrine regulation of hormone secretion and metabolism.

Adrenocorticotropic Hormone↗

Subtraction potential difference: In-vivo assay for mineralocorticoid activity.

Parallel fluctuations of potential difference (P.D.) across oral and rectal mucosa are probably related to the activity of autonomic nerves rather than adrenal steroids. Unlike rectal mucosa, oral mucosa does not respond to exogenous or endogenous aldosterone. Therefore subtraction of oral P.D. from rectal P.D. gives a closer indication of mineralocorticoid activity than does rectal P.D. alone. In normal subjects plasma-aldosterone correlated well with subtraction P.D. (r = 0.74; P is less than 0.001). A subtraction P.D. higher than 26 mV in subjects on a normal sodium intake indicated primary or secondary hyperaldosteronism; if the level was lower than 11 mV four hours after intramuscular injection of 0.25 mg tetracosactrin this suggested mineralocorticoid deficiency. Measurement of oral and rectal P.D. permits rapid and inexpensive diagnosis of aldosterone excess and deficiency. The method may also be used in study of the mineralocorticoid effect of other adrenal steroids: as assessed with this bioassay, the plasma 18-OH-deoxycorticosterone, which is raised in some patients with essential hypertension, lacked any in vivo mineralocorticoid activity.

Action Potentials↗

The development and application of a direct radioimmunoassay for plasma aldosterone using 125I-labeled ligand--comparison of three methods.

A direct, rapid, sensitive, and highly specific radioimmunoassay for plasma aldosterone has been developed using aldosterone conjugated to [125I]histamine as ligand and a highly specific aldosterone antiserum. This assay permits the direct measurement of plasma aldosterone without preliminary extraction or purification steps and hence allows a single technician to assay 500 samples in a week. An excellent correlation was obtained between the results of the direct assay and the levels measured after paper chromatography (n = 43, r = 0.99, P less than 0.001) or after extraction (n = 43, r = 0.99, P less than 0.001). The coefficients of variation for intra-assay and inter-assay determinations of samples from a normal plasma pool were 7.6% and 9.3%, respectively.

Aldosterone↗