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Biomedical subjects

G H Beastall

Publications and source records attributed to G H Beastall.

At least 91 records · Page 5Linked to original sources
PubMed1986

Inhibition by omeprazole of adrenocortical response to ACTH: clinical studies and experiments on bovine adrenal cortex in vitro.

Omeprazole, a substituted benzimidazole, is a potent inhibitor of gastric acid secretion which is currently being evaluated in patients with peptic ulcer and Zollinger-Ellison syndrome. Drugs which possess an imidazole nucleus have previously been shown to inhibit cortisol release from the adrenal cortex, secondary to inhibition of mitochondrial cytochrome P-450 dependent hydroxylation reactions. In a double-blind placebo-controlled crossover study in healthy male volunteers, omeprazole (60 mg daily for 7 days) did not alter basal cortisol levels. The peak cortisol response to ACTH stimulation was significantly reduced. Cortisol levels 60 min after ACTH were 824 +/- 27 nmol/l on omeprazole (mean +/- SEM), and 929 +/- 35 on placebo (P less than 0.005). In vitro, omeprazole caused a concentration-dependent inhibition of ACTH-stimulated cortisol release from isolated bovine adrenal cells (ED50 = 20 micrograms/ml). This was associated with a decrease in deoxycortisol synthesis. Therefore, unlike some other imidazole-containing drugs, the inhibitory effects of omeprazole are not entirely due to steroid 11 beta-hydroxylase inhibition. Substantial inhibition occurred at omeprazole concentrations which are higher than plasma levels normally achieved in clinical use. However, impairment of adrenocortical function may occur in patients on long-term high dose omeprazole treatment for Zollinger-Ellison syndrome.

Adrenal Cortex↗
PubMed1986

Effect of low-dose dopamine infusion on insulin and glucagon release in fasting normal man.

The effect of a low-dose infusion of dopamine on basal circulating concentrations of insulin, glucagon and glucose in six healthy male subjects is reported. Dopamine (0.1 microgram/kg/min) or placebo was given intravenously for 60 minutes. During infusion of the catecholamine, circulating plasma dopamine was 3.46 +/- 1 ng/ml. No change in circulating concentrations of insulin, glucagon and glucose were seen during infusion of dopamine when compared with placebo infusion. It is concluded that dopamine acting at a D2 receptor is unlikely to be of physiological importance in regulation of basal pancreatic islet cell function in man.

Blood Glucose↗
PubMed1986

Effect of oral verapamil on glibenclamide stimulated insulin secretion.

In order to study the effect of the calcium antagonist, verapamil, on glibenclamide stimulated insulin release, nine healthy fasted male volunteers were given 5 mg oral glibenclamide with either 120 mg oral verapamil or placebo in a double-blind crossover manner 1 week apart. Blood was withdrawn at intervals for drug, hormonal and glucose estimations. Concomitant administration of verapamil resulted in higher levels of glibenclamide at each time point (P less than 0.01) suggesting that verapamil interferes with glibenclamide metabolism. However, levels of plasma glucose, C-peptide, insulin and glucagon did not differ between the verapamil and placebo studies.

Adult↗
PubMed1986

A study of corticotroph adenomas in Cushing's disease: no evidence of intermediate lobe origin.

There is little evidence for a separate functional or anatomical intermediate lobe in the adult human pituitary gland. Nevertheless, Lamberts et al. (1982) proposed that a subgroup of corticotroph adenomas in Cushing's disease arise in that lobe and can be identified by the presence of argyrophil (? neural) fibres, and that these tumours are more often associated with corticotroph hyperplasia and hyperprolactinaemia than those arising in the anterior lobe. We have examined a series of corticotroph adenomas from patients with Cushing's disease for evidence of argyrophil fibres, and have correlated this with tumour site, corticotroph distribution in the para-adenomatous gland, serum PRL levels and PRL immunoreactive cells in the tumour. Argyrophil fibres were identified not only in tumours adjacent to the posterior lobe, but also in tumours situated deep in the anterior lobe. There was no correlation between the presence of fibres or the site of the tumour and corticotroph hyperplasia. Whilst the two patients with the highest serum PRL levels did have argyrophil fibres they also had a subpopulation of PRL immunoreactive cells in the tumour. On the basis of these results, we propose that the 'intermediate lobe' hypothesis as outlined above should not be accepted.

Adenoma↗
PubMed1986

Impaired thyrotrophin secretion following the administration of thyrotrophin-releasing hormone in type II diabetes mellitus.

Serum thyrotrophin has been measured before and after the intravenous administration of 200 micrograms of thyrotrophin-releasing hormone in 91 white subjects (33 stable diabetic patients and 58 healthy controls), none of whom had any clinical evidence of thyroid or pituitary dysfunction. Seven of the diabetic subjects failed to achieve a rise of serum thyrotrophin of greater than 2 mU/l above basal concentrations, as compared with only one of the control subjects (P = 0.006). The difference in response between diabetics and controls was confined to patients with Type II (non-insulin-dependent) diabetes: thus 5 of 13 Type II patients and 2 of 20 Type I (insulin-dependent) patients failed to show a normal response to thyrotrophin releasing hormone injection. No significant effect of glycaemic control on thyrotrophin responses was noted. These results suggest that Type II diabetes mellitus may be a cause of impaired thyrotrophin secretion in patients with no clinical evidence of pituitary disease. The mechanism for this impaired pituitary hormone release remains to be clarified.

Adolescent↗
PubMed1986

Assays for prolactin: guidelines for the provision of a clinical biochemistry service.

This paper summarises the views of the authors on the provision of a prolactin assay service. We discuss the pathophysiology of prolactin secretion and the clinical indications that arise from that. We cover the rather complex issue of the definition of normal and elevated prolactin levels. From these considerations, certain guidelines on the analytical performance of prolactin assays and their provision in a clinical biochemistry service are given. The extent to which currently available methods and performance as revealed by the UK External Quality Assessment Scheme (EQAS) match these guidelines are described and certain conclusions are reached. Finally, probable future developments are briefly discussed. The main conclusions and recommendations are as follows: Reagents of appropriate quality are available to enable prolactin immunoassays to be provided in UK clinical biochemistry laboratories. These are provided either separately or in the form of kits from both commercial and NHS sources. There is no requirement for individual laboratories to undertake their own antiserum production or prolactin iodination. Acceptable performance (as defined using internal QC procedures and the UK EQAS) is achievable using these reagents/kits, although one commercial kit shows a consistent marked negative bias. Reference ranges, including 'normal ranges', show considerable between-centre variability. Many centres have not established their own ranges, even those using in-house methods. Reference ranges for use in clinical biochemistry laboratories are proposed in this report. Some general guidance on the provision of a prolactin service is given, although this does not differ in principle from that appropriate for other peptide hormone analytes. There is no evidence that centres with small workloads perform any worse than average, although it may be more cost-efficient for such centres to send the samples elsewhere. As with other peptide analytes, non-isotopic immunometric methodology is likely to replace current radioimmunoassay methods in the near future.

Female↗
PubMed1986

Neonatal screening for congenital adrenal hyperplasia: a programme based on a novel direct radioimmunoassay for 17-hydroxyprogesterone in blood spots.

We have assessed the feasibility of screening newborn babies for congenital adrenal hyperplasia (CAH) by the direct measurement of 17-hydroxyprogesterone (17-OHP) in blood spots collected on filter paper (Guthrie cards) for the phenylketonuria, hypothyroidism and galactosaemia screening programmes run in Scotland. The procedure described for CAH uses an iodinated 17-OHP tracer and a specific 17-OHP antiserum sheathed within semipermeable nylon microcapsules. The method does not require a solvent extraction step, is inexpensive, precise, efficient and, therefore, practical for large-scale use. With this system the value of a neonatal screening programme was assessed in a retrospective analysis and a prospective trial. The retrospective study of 15 paediatric cases of CAH illustrated that at least half were not diagnosed within 3 weeks of birth. Analysis of the original Guthrie card samples revealed increased levels of 17-OHP in all cases. The prevalence of CAH as calculated in the retrospective study was 1 in 20 907 with a range (within 95% confidence limits) of from 1 in 12 675 to 1 in 32 604 (n = 301 450). In the prospective trial a total of 92 051 consecutive samples was screened. Five cases of CAH were correctly identified with a current false positive rate of 0.042%. Analysis of urinary steroids confirmed defective adrenal 21-hydroxylase activity in all positive cases. In the prospective trial the prevalence was 1 in 18 401 with a range of from 1 in 7422 to 1 in 50 006. We conclude that mass screening for CAH is both feasible and desirable.

Adrenal Hyperplasia, Congenital↗
PubMed1986

Androgenic status and sexual function in males with rheumatoid arthritis and ankylosing spondylitis.

The pituitary-testicular axis was investigated in 31 males with rheumatoid arthritis (age range 19-60 years, median 55 years) and 33 males with ankylosing spondylitis (age range 22-55 years, median 37 years) and compared with a control group of 95 normal male volunteers. Using analysis of covariance, patients with rheumatoid arthritis showed significantly lower serum testosterone (p less than 0.05) and derived free testosterone (p less than 0.01) concentrations and significantly higher serum LH and FSH concentrations (p less than 0.05) compared with controls. All patients had normal serum prolactin and cortisol concentrations. Serum testosterone correlated with ESR, haemoglobin concentrations and rheumatoid factor titres (r = -0.448, p less than 0.02; r = 0.440, p less than 0.02; r = -0.360, p less than 0.05 respectively) in the rheumatoid patients. Although there was a significant negative correlation between ESR and haemoglobin concentrations (p less than 0.005) in the patients with ankylosing spondylitis, neither variable correlated with serum testosterone concentrations. There was no association between testicular dysfunction and the presence of extra-articular features of rheumatoid arthritis. Ten patients (33 per cent) with rheumatoid arthritis and four (13 per cent) with ankylosing spondylitis admitted to periods of impotence while 15 (50 per cent) of the former and 12 (39 per cent) of the latter had periods of decreased libido. There was no evidence for increased rates of infertility in either group.

Adult↗
PubMed1985

Effect of long term hormone replacement on plasma prolactin concentrations in women after oophorectomy.

Plasma prolactin concentrations were studied in 88 oophorectomised women who had been receiving mestranol or placebo for three to 11 years. Thirty one of them were also studied under basal conditions and by tests with thyrotrophin releasing hormone. Under basal conditions the mean prolactin concentration was higher in the oestrogen treated group but under non-rested, clinic conditions the difference was lost because of a rise in prolactin value in the placebo group only. Hence the groups showed a different prolactin response to the mild stress of clinic attendance but the same proportionate responsiveness to thyrotrophin releasing hormone. The data suggest that long term hormone replacement has no significant effect on circulating prolactin concentrations under non-rested, everyday conditions and that the prolactin stimulating effects of minor stress and oestrogen may share a similar mechanism.

Aged↗
PubMed1985

Endocrine and protein response to elective surgery: effect of nursing at two different environmental temperatures.

Twenty male patients undergoing elective abdominal surgery were studied on one control day pre-operatively and for the first 4 days postoperatively at an environmental temperature of either 20 degrees C or 28 degrees C. Glucose, insulin, growth hormone and urinary catecholamine levels all rose significantly on the first postoperative day returning to within normal limits by day 4. Urine nitrogen excretion also increased significantly postoperatively in both groups. Environmental temperature did not influence these responses. Concentrations of C-reactive protein and a1-antichymotrypsin increased significantly on the first postoperative day and were returning to normal by day 4 while concentrations of haptoglobin, a1-antitrypsin and a1-acid glycoprotein, which also showed a significant increase, remained elevated at the end of the study. Concentrations of albumin, transferrin, a2-macroglobulin, prealbumin and retinol binding protein all decreased significantly following operation. Elevated environmental temperature did not affect the protein response to surgery. Urine cortisol and 17-hydroxycorticosteroid excretion rose significantly postoperatively and remained elevated throughout the study. Patients nursed at 28 degrees C showed significantly lower postoperative excretion of both hormones than patients nursed at 20 degrees C.

Journal Article↗
PubMed1985

Effect of low-dose dopamine infusion on basal and stimulated TSH and prolactin concentrations in man.

Dopamine (DA) infused at pharmacological doses in man inhibits thyrotrophin (TSH) secretion, although the physiological significance of this observation is unclear. The effect of low-dose DA infusion (0.1 microgram/kg/min) on TSH and prolactin (PRL) concentrations during stimulation with thyrotrophin releasing hormone (TRH) in normal male subjects is reported. Six subjects were given intravenous DA or placebo infusions for 165 min on separate days. A bolus of TRH (7.5 micrograms) was given at + 90 min, followed by infusion of the tripeptide (750 ng/min) for 45 min during both DA and placebo studies. In all subjects TRH administration caused a small rise in TSH which was partially inhibited by DA (peak 5.73 +/- 0.85 mU/l vs 4.58 +/- 1.09, P less than 0.05). PRL response to TRH was almost totally inhibited by DA (620 +/- 164 mU/l vs 234 +/- 96, P less than 0.05); integrated TSH and PRL responses to TRH were similarly inhibited by DA. Circulating plasma DA concentration during infusion of the catecholamine was 3.46 +/- 1.00 ng/ml, which is within the range reported in pituitary stalk plasma of other species. These data support the hypothesis that DA is a physiological modulator of TSH secretion in normal man. Major differences in the time course of TSH and PRL responses to TRH, and in the suppressive effect of DA on these responses suggest that there are fundamental differences in stimulus-secretion coupling for TRH and the lactotroph and thyrotroph.

Adult↗
PubMed1985

Comparison of oral glucose loading and intravenous glucagon injection as stimuli to C-peptide secretion in normal men.

In 10 healthy men, we have compared the respective effects of an intravenous injection of glucagon (1 mg) and an oral glucose load (75 G) in eliciting the release of C-peptide and insulin from the pancreas. Serum C-peptide and insulin concentrations increased respectively to median values of 190% and 500% at 6 minutes after glucagon injection, and 344% and 794% at 30 minutes and 268% and 278% at 60 minutes following glucose ingestion. The oral glucose load was as effective as glucagon injection in testing beta cell function and was free from the unpleasant side effects (nausea, vomiting, syncope) commonly associated with glucagon. We conclude that oral glucose loading is probably the test of choice to elicit C-peptide release when screening populations of normal subjects for adequacy of beta cell function.

Adult↗
PubMed1985

Endocrine responses to marathon running.

We have examined the hormone status of ten healthy adult males who completed the Glasgow marathon. Serum thyroxine, free thyroxine, triiodothyronine and thyroid stimulating hormone were unaffected by the exertion. Serum cortisol as well as other steroid hormones, androstenedione, dehydroepiandrosterone sulphate and oestradiol showed distinct rises (p less than 0.01) but serum testosterone fell significantly (p less than 0.01). There was no change in sex hormone binding globulin capacity but a significant fall in LH levels (p less than 0.05) accompanied the fall in serum testosterone. The mechanism of the fall in serum testosterone in this situation requires clarification but it is unlikely to have adverse consequences.

Adrenal Cortex Hormones↗
PubMed1985

Evaluation of a time-resolved immunofluorometric assay for serum thyroid stimulating hormone.

The LKB 'Delfia, immunofluorometric assay for serum TSH has been evaluated. The assay is simple and rapid to perform and is capable of processing in excess of 100 specimens within a working day. The sensitivity of the assay is 0.05 microU/L, with a working range extending beyond 324 microU/L. The change in signal at each point over the standard curve approaches 1000-fold, significantly greater than that of a typical immunoradiometric assay. Mean figures for intra-assay and inter-assay precision were 4.7% and 8.6% CV, respectively. Mean recovery of added TSH was 98.3%, and samples containing high levels of endogenous TSH diluted parallel to the standard curve. The method showed good correlation with an immunoradiometric assay for TSH. The reference ranges for clinically defined groups of subjects were euthyroid 0.47-3.84 microU/L (n = 83); primary hypothyroidism 15--greater than 324 microU/L (n = 28); thyrotoxicosis less than 0.05 microU/L (n = 46). It is concluded that the 'Delfia' assay offers the clinical biochemistry laboratory an attractive and reliable alternative to a sensitive immunoradiometric assay for serum TSH.

Evaluation Studies as Topic↗
PubMed1985

Endocrine studies in cyanotic congenital heart disease.

Seven male patients with cyanotic congenital heart disease were studied. Serum testosterone, androstenedione, dehydroepiandrosterone, thyroxine and triiodothyronine levels did not differ significantly from control values. Thyroid stimulating hormone and prolactin responses to injected thyrotrophin releasing hormone were normal. Impaired gonadotrophin responses to injected gonadotrophin releasing hormone were noted in two patients. The hypothalmic-pituitary-testicular axis appears to be better preserved in cyanotic congenital heart disease than in chronic obstructive airways disease and restrictive lung disease for a similar degree of hypoxia. Possible explanations are discussed.

Adolescent↗
PubMed1985

The effect of omeprazole on insulin induced gastric secretion in man.

The effect of oral omeprazole on insulin induced gastric secretion was studied in 12 healthy subjects. Each subject participated in two secretory tests receiving an intravenous infusion of insulin (0.03 units/kg/h) and being randomly allocated to receive 30mg or 60mg omeprazole suspended in 100ml water containing 16 mmol NaHCO3 on the second study day. Peak plasma concentrations of omeprazole were achieved within 30 minutes of administration in all but one subject and plasma half life was 30 minutes. Mean peak stimulated acid output in the six subjects receiving 30mg omeprazole was reduced to 4.3 +/- S.E. 1.8 mmol/h from a control value of 16.8 +/- 2.2 mmol/h (p less than 0.05) and in six subjects receiving 60mg omeprazole, mean peak output fell to 3.4 +/- 2.1 mmol/h from a control value of 12.3 +/- 2.6 mmol/h (p less than 0.05). The two doses of omeprazole produced similar reduction in acid secretion (74% and 73% respectively) but neither dose affected pepsin secretion. Both doses of omeprazole were associated with a small statistically insignificant increase in the plasma gastrin response to insulin infusion.

Adult↗