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Biomedical subjects

R A Donald

Publications and source records attributed to R A Donald.

At least 145 records · Page 8Linked to original sources

Fluctuating ovarian function in a perimenopausal women.

Plasma follicle stimulating hormone (FSH) and luteinising hormone (LH) concentrations, and pregnanediol and oestrogen excretion rates, were measured in a perimenopausal woman from the first appearance of oligomenorrhoea until the onset of severe and persistent hot flushes two years later. Postmenopausal episodes characterised by hot flashes, amenorrhoea, high FSH levels (greater than or equal to 5IU/L) and low urinary oestrogens (less than or equal to 50 nmol/24hr), were followed by menstrual cycles in which the FSH levels were low (less than 5 IU/L) and there was an ovulatory pattern of oestrogen and pregnanediol excretion. An unusual association of high urinary oestrogens (greater than or equal to 50 nmol/24hr) with high gonadotrophin levels was observed on several occasions. The transient postmenopausal episodes were biochemically and symptomatically indistinguishable from the permanent amenorrhoea of postmenopausal women.

Climacteric↗

Lack of effect of prolactin suppression on plasma dehydroepiandrosterone sulphate.

In twelve patients with hyperprolactinaemia, treatment which reduced plasma prolactin from a mean of 531 microgram/l (range 68-3500 microgram/1) to 8.3 microgram/l (0-27 microgram/l), caused no significant change in plasma dehydroepiandrosterone sulphate (DHA-SO4). Pre-treatment levels of DHA-SO4 were within the normal range in eleven out of twelve cases. The results do not support for claims that prolactin excess is associated with an increase in circulating DHA-SO4.

Adolescent↗

Intermittent Cushing's disease with spontaneous remission.

A patient with well documented Cushing's syndrome, associated with excessive secretion of ACTH, was studied over a 20 month period. During this time there were three episodes of spontaneous biochemical remission and except for a 7 day period of exacerbation the patient has had normal cortisol production for the last 15 months. During this recent prolonged remission period, repeat pituitary function testing demonstrated persistent abnormalities of the hypothalamic pituitary axis, in that ACTH failed to respond to a hypoglycaemic stimulus. However in all other respects adrenal function was normal with preservation of diurnal rhythmicity of cortisol and ACTH, and intact dexamethasone suppressability of cortisol. The additional unusual features of normal GH and TSH responses to stimulation, during either remission or exacerbation, suggest a subtle and localized hypothalamic defect in this case.

Adrenocorticotropic Hormone↗

A true hermaphrodite dispermic chimera with 46,XX and 46,XY karyotypes.

A 16-year-old male with hypospadias and gynaecomastia had a rudimentary uterus with a right Fallopian tube and ovary; the left gonad was a functioning testis. Cytogenetic studies showed cells with 46,XX and 46,XY sex chromosomes in cultured blood, skin and gonadal tissues. Cells with the 46,XX constitution predominated in all tissues. Extensive investigations failed to demonstrate blood cell and serum chimerism, but there was little genetic variation of these characters between family members. Cytogenetic studies demonstrated that the father had contributed different marker chromosomes to the 46,XY and 46,XX cell lines of the propositus, whereas the mother had contributed the same two informative markers to both cell lines. The patient was a chimera with two diploid cell lines of different sex that had developed from the products of two separate acts of syngamy. Dispermy was demonstrated, and, whereas there was no evidence of different maternal contributions to the chimeric cell lines, uncertainty remains that these were identical.

Adolescent↗

The association between diabetic retinopathy and skeletal muscle capillary basal lamina thickening corrected for the influence of age and duration of diabetes.

The association between an objective measure of diabetic retinopathy and skeletal muscle capillary basal lamina thickness was examined in a group of 30 male insulin-treated diabetic subjects, mean age (+/- SD) 44.6 +/- 13.2 yr, duration of diabetes 21.2 +/- 11.2 yr, % ideal body weight (% IBW) 106 +/- 11%. In addition, muscle capillary basal lamina width was measured in a group of 18 nondiabeitc men, mean age 40.7 +/- 16.3 yr and % IBW 118 +/- 23%. The muscle capillary width of the diabetic subjects was significantly greater than that of the nondiabetic group (P less than 0.01), but the values of the two overlapped considerably. In the diabetic group, there was a significant association of basal lamina width with age (P less than 0.01) but not with duration of diabetes. The association between extent of retinopathy and muscle capillary basal lamina width was not strong. The findings of the study do not therefore support the use of an estimate of muscle capillary basal lamina thickness as a single representative measure of diabetic microangiopathy.

Adult↗

Clinical use of plasma renin assays.

The use of plasma renin assays in clinical practice is reviewed and experience with an assay for plasma renin activity (PRA) is reported. In normal subjects, 10am ambulant PRA was significantly related to plasma angiotensin II levels but not related to daily urine sodium exretion in these subjects consuming normal diets. PRA was suppressed in patients with mineralocorticoid hypertension and in a small proportion of patients with essential hypertension. Very high values were observed in patients with untreated primary adrenal insufficiency, treatment of which resulted in a prompt fall of PRA to normal. PRA was usually normal in adrenalectomised patients and those with chronic adrenal insufficiency receiving satisfactory steroid replacement therapy. It is concluded that provided standardised conditions are used for the collection and assay, PRA is helpful in the assessment of hypokalaemic hypertension as well as in the early detection and management of patients with primary adrenal insufficiency or related conditions of salt wasting.

Adolescent↗

Plasma ACTH and cortisol profiles in Addisonian patients receiving conventional substitution therapy.

Plasma ACTH and cortisol profiles were studied over 24 h in five Addisonian patients maintained in good health by conventional gluco- and mineralocorticoid treatment. Patients received their usual treatment (15--30 mg cortisol daily) in divided doses at 08.00 and 16.00 hours. Plasma cortisol concentrations differed from those of control subjects in being higher from 08.00 hours-noon and 17.00-18.00 hours and were unmeasurable (less than 20 nmol/l) during the period of active cortisol secretion (03.00-08.00 hours) observed in normal subjects. Peak plasma ACTH levels (618- greater than 1600 ng/l) occurred at 08.00-09.00 hours in the Addisonian patients and were much greater than those seen in control subjects (60-220 ng/l). Despite this, plasma ACTH fell promptly within 3 h of the morning dose to less than 100 ng/l and levels were indistinguishable from those seen in normal subjects over the period 12.00-02.00 hours. These results show that there are substantial differences between treated Addisonian and control subjects in respect of plasma cortisol and ACTH concentrations. The findings may lead to a better understanding of ACTH-cortisol relationships in disease states, including congenital adrenal hyperplasia where control of excessive ACTH secretion is clinically desirable.

Addison Disease↗

Hormonal responses during treatment of acute diabetic ketoacidosis with constant insulin infusions.

Changes in glucagon, growth hormone (GH), cortisol, renin and aldosterone accompanying the metabolic disturbances and dehydration of severe diabetic ketoacidosis were studied over a 24 h period in eight patients treated with a constant intravenous insulin infusion. Mean steady state plasma-free insulin levels achieved were 28.6--49 mu/1 in patients receiving 2 u/h but a satisfactory rate of fall of glucose was not always obtained until the infusion dose was increased to 4 u/h or more. The total insulin dose administered was positively correlated with the level of plasma glucagon and cortisol on admission. During insulin infusion, both glucagon and cortisol fell but the rate of fall was not related to dose or plasma level of free insulin achieved. In six of eight patients studied increments in plasma GH above admission levels were observed during insulin treatment. Admission values of both plasma renin activity and plasma aldosterone were raised. The renin levels were highest in newly diagnosed diabetics, and two patients with long-established diabetes showed only small increments despite profound dehydration. Plasma renin activity, but not plasma aldosterone correlated with the fluid and sodium retention over the initial 24 h treatment period, but not with potassium requirements. The urinary excretion rates of the small molecular weight proteins GH and insulin, were considerably elevated over the treatment and convalescent periods.

Acute Disease↗

Treatment of amenorrhoea, galactorrhoea and hypogonadism with bromocriptine.

The effect of bromocriptine administration was studied in 34 patients, whose presenting symptoms included amenorrhoea, galactorrhoea, infertility, dyspareunia, delayed puberty, and impotence. Two patients were found to have raised plasma prolactin values during investigation for acromegaly. With the exception of three individuals all patients had hyperprolactinaemia. Pituitary fossa enlargement or asymmetry was reported in 16 patients and one patient had primary hypothyroidism. Virtually all patients complained of side effects when first starting bromocriptine but only two patients were unable to tolerate prolonged therapy with doses which ranged from 5--40 mg daily. A single oral dose of 2.5 mg resulted in a greater than 50% reduction in plasma prolactin within five hours in 22 of 26 patients. Over the course of one month, five patients with significant pituitary fossa enlargement appeared to show less rapid suppression of plasma prolactin than five patients without fossa enlargement. At two months this trend was still evident but eventually all patients showed acceptable control of plasma prolactin, with the exception of one patient who required pituitary surgery. Galactorrhoea ceased in 13 of 15 patients, menstrual periods resumed in ten of 13 patients, two patients becoming pregnant first. Potency returned and puberty proceeded in two hypogonadal males. Six of the nine patients requesting treatment for infertility became pregnant. It is concluded that bromocriptine provides effective treatment for galactorrhoea, amenorrhoea or gonadal disorders when there is associated hyperprolactinaemia.

Adolescent↗

Assessment of ovarian function in perimenopausal women after stopping oral contraceptives.

Ovarian function was assessed by measuring plasma gonadotrophins, urinary oestrogen and urinary pregnanediol levels, every week for four weeks, in 34 women, aged 45 to 57 years, after withdrawal of oral contraceptive therapy. A rise in urinary pregnanediol excretion occurred in 14 patients suggesting that ovulation had occurred and that these patients were "premenopausal". Elevated serum gonadotrophin values and persistently low urinary oestrogen and pregnanediol excretion occurred in 13 patients suggesting ovarian failure or a "postmenopausal" state. However, one apparently "postmenopausal" patient later showed hormonal evidence of ovulation, indicating fluctuation in ovarian function. There were 7 patients with "indeterminate" hormone profiles whose ovarian function was difficult to assess. All patients excreting more than 45 nmol of oestrogen a day had a spontaneous period within 45 days of stopping hormone therapy.

Adult↗

Licorice raises urinary cortisol in man.

The finding that urine cortisol excretion was increased in patients with hypokalaemic hypertension induced by licorice addiction led to this study on the effect of licorice in normal subjects. Thirteen normal volunteers ate either 100 or 200 g licorice for 1-4 weeks and assessment of pituitary-adrenal function was made before, during, and 1 week after cessation of licorice ingestion. Urine cortisol excretion more than doubled in 10 of 13 subjects (mean, 33.8 +/- 15.6 SD before and 83.3 +/- 56 SD micrograms/24 h at 1 week after commencing licorice) and excretion rates similar to those observed in Cushing's syndrome were seen in 7 subjects (range, 91-226, compared to normal range of 11-82 micrograms/24 h). Urine cortisol excretion remained significantly elevated (P less than 0.01) above control levels for at least 1 week after licorice was withdrawn. Despite these increases, urinary steroid metabolite (tetrahydrocortisol, tetrahydrocortisone, tetrahydro-11-deoxycortisol, 17-ketogenicsteroids, and 17-ketosteroids) excretion was not affected, plasma cortisol and ACTH values were unchanged, and normal 0800-1600-h diurnal variation of plasma cortisol was maintained. The direct intraadrenal infusion of the active mineralocorticoid component of licorice, glycyrrhetinic acid, in two sheep with autotransplanted adrenal glands failed to stimulate cortisol secretion acutely. It is concluded from these studies that the licorice-induced changes in cortisol excretion are not a result of adrenocoritcal stimulation but more likely represent a change in the renal handling of cortisol.

Adenoma↗

Antibody binding of insulin in diabetic ketoacidosis.

This study investigates the effects of insulin antibody binding on free insulin levels measured in patients with acute diabetic ketoacidosis receiving insulin by constant infusion. In spite of antibody binding ranging from 10 to 90 per cent of the total circulating insulin, the steady state concentrations of free insulin were similar to those observed in individuals on identical infusion rates but without insulin-binding antibodies. However, the levels of free insulin in two patients were substantially lower than expected for the rate of insulin infusion, even though levels of bound insulin were not greatly elevated. An infusion rate of at least 4 U. per hour produced satisfactory rate of fall of plasma glucose, whereas lower dose regimens (2 U. per hour)--producing steady state free insulin concentrations ranging from 28 to 49 mU. per liter in different subjects--were unreliable in controlling the metabolic abnormalities of diabetic ketoacidosis.

Adolescent↗

The influence of glucagon on sodium retention after fasting.

Two groups of five obese female subjects, having undergone a ten day therapeutic fast, were fed with either glucose 50 g/day or with L-alanine 50 g/day for three days. Plasma glucagon concentrations and urinary electrolyte excretion were compared in the two groups. Although 4.00pm plasma glucagon concentrations during refeeding were significantly greater in the alanine refeed group (P less than 0.05) the reduction in urinary sodium excretion in each of the two groups was identical. These observations do not support the hypothesis that glucose induced suppression of plasma glucagon concentrations is a mechanism whereby carbohydrate refeeding produces post-fast urinary sodium retention.

Adolescent↗

Effect of eating liquorice on the renin-angiotensin aldosterone axis in normal subjects.

The effect of confectionery liquorice on electrolyte status and the renin-angiotensin-aldosterone (RAA) axis was studied in 14 healthy volunteers. They ate liquorice in daily doses of 100 g or 200 g (equivalent to 0-7-1-4 g glycyrrhizinic acid) for one to four weeks. Plasma potassium concentrations fell by over 0-3 mmol/l in 11 people, including four who had to be withdrawn from the study because of hypokalaemia. One or more values of the RAA axis, especially plasma renin activity and urinary aldosterone concentrations, were considerably depressed in all subjects. These results show that potentially serious metabolic effects may occur in some people who eat modest amounts of liquorice daily for less than a week.

Adult↗