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Biomedical subjects

M F Scanlon

Publications and source records attributed to M F Scanlon.

196 records · Page 11Linked to original sources
PubMed1977

Evidence for dopaminergic control of thyrotrophin secretion in man.

After administration of the dopamine-receptor-blocking drug, metoclopramide (10 mg orally), there is significant release of thyrotrophin (T.S.H.) in hypothyroid patients which is not evident in euthyroid subjects. This is not due to spontaneous fluctuation in basal T.S.H. levels, and it indicates inhibitory dopaminergic control of T.S.H. release in man. The lack of significant T.S.H. release in euthyroid subjects may be due to the inhibitory effects of normal circulating levels of T3 and T4 on T.S.H. release. The T.S.H. response in hypothyroidism is significantly correlated with both T3 and T4 levels, suggesting suppression of this inhibitory pathway in increasingly severe hypothyroidism.

Administration, Oral↗
PubMed1977

Effects of nomifensine, an inhibitor of endogenous catecholamine re-uptake, in acromegaly, in hyperprolactinaemia, and against stimulated prolactin release in man.

1. Nomifensine, an inhibitor of endogenous catecholamine re-uptake, did not affect the growth hormone (GH) or prolactin levels in patients with acromegaly or hyperprolactinaemia. It does not, therefore, have any therapeutic role in these conditions at the dosage used in this study. 2. It had no effect on thyrotrophin-releasing hormone (TRH)-induced thyrotrophin (TSH) or prolactin release in males, yet caused marked suppression of monoiodotyrosine (MIT)-induced prolactin release in males but not in females. 3. The significant suppression of MIT-induced prolactin release in males is likely to reflect the dopamine (DA) agonist activity of the drug and its lack of effect in the other situations tested could be dose related. 4. It is proposed that the difference in male and female patterns of prolactin response to MIT after nomifensine, could be due to a "damping" effect of oestrogen on the hypothalamic dopaminergic system.

Acromegaly↗
PubMedDate not supplied

Somatic characteristics and cardiovascular risk factors in growth hormone deficiency: a randomized, double-blind, placebo-controlled study of the effect of treatment with recombinant human growth hormone.

The purpose of the present study was to identify the effect of treatment with recombinant human growth hormone (rhGH) on seven somatic characteristics and eight clinical cardiovascular risk factors. Twenty-seven male and 24 female patients between the ages of 21 and 60 years were examined. The investigation was a double-blind, placebo-controlled study of 12 months duration. Patients were assigned randomly to treatment (T) and placebo (P) groups. In the first 6 months group T received rhGH and group P placebo. In the second 6 months both groups received rhGH. Complete data were available for 23 males and 20 females. Increments were calculated between 6 months -BL (increment 1) and 12-6 months (increment 2) in both T and P groups. Apart from the somatotype, data were analysed with a 2 x 2 mixed analysis of variance (ANOVA) using treatment (rhGH and placebo) and time (increments 1 and 2). Somatotype data were analysed using a 2 x 3 multivariate ANOVA. Three significant interactions were identified in males: waist circumference (P = 0.006), trunk fat (P = 0.0001), and conicity index (P = 0.001). The only significant interaction in females was trunk fat (P = 0.006). In general, treatment and placebo groups responded differently by time and treatment. Responses were similar in males and females. In the first 6 months when group P was on placebo, waist circumference, trunk fat, and conicity index increased slightly; with group T on rhGH somatic variables declined markedly. In the second 6 months when both groups received rhGH there was a marked decline in group P and a continued decline (but less steeply) in group T. In males there were significant decreases in endomorphy in group T and increases in mesomorphy in group P. In females the somatotype remained stable. There were no significant interactions in clinical cardiovascular risk factors in either males or females. Favourable responses occurred in male and female lipid profiles, although these were not significant. It was concluded that in males waist circumference, trunk fat, conicity index, and somatotype responded significantly to treatment with rhGH; in females the only significant response was trunk fat.

Adult↗
PubMedDate not supplied

Differential responses of rat cerebral somatostatinergic and cholinergic cells to glutamate agonists.

Reductions in cortical somatostatin (SRIH) and choline acetyl-transferase (ChAT) are major biochemical deficits in Alzheimer disease (AD). SRIH and ChAT were measured in fetal rat cerebral neurons after exposure to the glutamate agonists N-methyl-D-aspartate (NMDA), kainate (KA), and quisqualate (Q). NMDA (96 h incubation) stimulated SRIH release and content in a dose-dependent manner with a Bmax of 10(-5)M and EC50 of 2-3 x 10(-6)M. KA showed a small stimulation in SRIH levels at 10(-5)M, but produced marked inhibition at 10(-4)M. Q decreased both intracellular and secreted SRIH. KA (51-76% of basal) and Q (27-56% of basal) but not NMDA (91-114% of basal) also inhibited the incorporation of [35S]methionine into proteins. In similar experiments 10(-4)M Q (23 +/- 9% of basal) and KA (20 +/- 3% of basal) but not NMDA (80 +/- 16% of basal) reduced ChAT levels in hypothalamic/septal cultures. These inhibitory actions on ChAT activity by KA and Q were reversed by gamma-glutamyltaurine (GT) but not by 2-amino-5-phosphonopentanoic acid (AP5). Chronic NMDA exposure partially inhibited muscarinic acetylcholine receptor (mAChR) mediated inositol phospholipid (PI) turnover, whereas it was abolished after KA and Q pretreatment. These findings suggest that in cerebral cell cultures, NMDA has a stimulatory action on somatostatinergic neurons and non-NMDA receptor agonism could play an important role in EAA-mediated neural damage.

Animals↗
PubMedDate not supplied

Catecholaminergic interactions in the regulation of thyrotropin (TSH) secretion in man.

The TSH responses to the catecholamine depleting agent monoiodotyrosine (1 g po) and the dopamine receptor blocking drug metoclopramide (10 mg po) have been compared in euthyroid and hypothyroid subjects. Both drugs lead to a prompt and significant rise in TSH levels (peak values at 60-75 min) which is very much greater in hypothyroid than euthyroid subjects. The findings lend further support to the inhibitory role of dopamine in the control of TSH release in man, since TSH release follows either dopamine depletion with monoiodotyrosine or dopamine receptor blockade with metoclopramide.

Adolescent↗
PubMedDate not supplied

Strength and its relationship to changes in fat-free mass, total body potassium, total body water and IGF-1 in adults with growth hormone deficiency: effect of treatment with growth hormone.

The present investigation examined changes in strength in growth hormone deficient (GHD) adults following treatment with recombinant human growth hormone (rhGH), and assessed their relationship to changes in fat-free mass (FFM), total body potassium (TBK), total body water (TBW), the concentration of TBK and TBW per kg FFM, and insulin like growth factor-1 (IGF-1). The investigation was double-blind and placebo-controlled for a period of 6 months; this was followed by a period of open treatment for a further 6 months. Patients were assigned randomly to experimental (E) and control (C) groups. In the first 6 months group E received rhGH and group C placebo; in the second 6 months both groups received rhGH. Serial data were analysed for 23 males (11 group E, 12 group C) and 20 females (10 group E, 10 group C). Body composition was assessed by dual energy X-ray absorptiometry, TBK and TBW. Muscle strength was recorded for arm flexion, leg extension and hand grip. Significant increases in FFM occurred in the first 6 months in group E (2.3 kg males, 1.4 kg females) and in the second 6 months in group C (2.4 kg males, 1.4 kg females). There was a modest increase in absolute strength with time, although only three increments were significant (knee extension in group E males and arm flexion in groups E and C females), all of which occurred during the 6-12 month period. Allometric scaling did not improve the identification of significant increments of strength. The mean concentrations of TBK (males 57.0-58.6, females 51.4-53.9 mmol) and TBW (males 0.65-0.69, females 0.65-0.68 l) per kg FFM, were significantly smaller at all stages of the trial than the reference values, suggesting that treatment had not fully normalized these variables. Likewise, the relationship between most of the increments of regional and total strength, and the corresponding increments of FFM, were generally poor and not significant. It was concluded that the reduced concentrations of TBK and TBW per kg FFM, which may be the effect of an inappropriate dose regime or mode of delivery, may, in part, contribute to the anomaly between increases in strength and FFM.

Adult↗
PubMedDate not supplied

Modulation of glucose and growth hormone responses to meals and exercise in type 1 diabetes by cholinergic muscarinic blockade.

Anticholinergic drugs suppress nocturnal and exercise-related growth hormone (GH) secretion in Type 1 diabetes; nocturnal GH suppression is associated with a fall in fasting plasma glucose levels. The aim of this study was to assess the effect of GH suppression on glucose levels following a period of meals and exercise in physiological pattern. Six Type 1 diabetic men recruited from the outpatient clinic were studied in random order at least 1 week apart. After an overnight fast subjects received two-thirds of their usual subcutaneous insulin and either 200 mg oral pirenzepine or placebo at time 0 min. Between 90 and 120 min subjects exercised continuously on an ergometric cycle. Standard meals or snacks were eaten at 30, 150, 270, and 390 min. Venous blood was collected from an indwelling cannula between 0 and 570 min. The mean incremental rise in plasma glucose after breakfast (delta peak/90 min) was 2.6 +/- 0.5 (mean +/- SEM mmol l-1 (pirenzepine) vs 4.5 +/- 0.8 (placebo)), p < 0.05. Following exercise the fall in plasma glucose (delta gluc90-240 min) was 6.4 +/- 1.9 (pirenzepine) vs 2.0 +/- 1.3 (placebo), p < 0.005. The exercise-related peak rise in GH was 12.6 +/- 3.3 (pirenzepine) vs 28.5 +/- 6.0 mU l-1 (placebo), p = 0.08. Excluding one outlying result there was an inverse correlation between the integrated exercise-related increase in GH between 90 and 240 min and the fall in glucose over the corresponding time period (n = 11, r = -0.75, p = 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Early-morning hyperglycemia in IDDM. Acute effects of cholinergic blockade.

Growth hormone (GH) hypersecretion in insulin-dependent diabetes mellitus (IDDM) subjects has been shown to be causally related to early-morning hyperglycemia. We studied the effect of nocturnal GH suppression on acute glycemic control in six IDDM patients during a constant overnight insulin infusion (0.075 mU.kg-1.min-1). In control experiments (infusion of insulin alone), plasma glucose increased from 5.6 +/- 0.6 mM at 2400 to 11.1 +/- 1.3 mM at 0900 (P = .0024). When in addition the cholinergic muscarinic antagonist pirenzepine was given (100 mg at 2200 and again at 2400), plasma glucose increased from 5.6 +/- 0.3 mM at 2400 to 8.4 +/- 1.4 mM at 0900 (P greater than .05). The nocturnal surges of GH that were demonstrated in all patients during the control nights were suppressed during the treatment nights. There were no significant changes in insulin, cortisol, or epinephrine concentrations. Mean glucagon and norepinephrine concentrations. Mean glucagon and norepinephrine concentrations were reduced from 127 +/- 2.7 ng/L and 8.7 +/- 0.5 nM to 101 +/- 1.9 ng/L (P less than .001) and 3.5 +/- 0.2 nM (P less than .001) on control and treatment nights, respectively. Neither glucagon nor norepinephrine concentrations changed significantly between 2400 and 0900 on either control or treatment nights. We conclude that nocturnal GH suppression by pirenzepine during a constant low-rate insulin infusion is associated with an attenuation of the early-morning plasma glucose rise.

Adult↗
PubMedDate not supplied

Increasing thyroxine requirements in primary hypothyroidism: don't forget the urinalysis!

Rising thyroid stimulating hormone (TSH) levels in patients being treated for primary hypothyroidism usually indicate poor compliance with thyroxine therapy. In rare instances, drugs or diseases affecting absorption of thyroxine or drugs that accelerate thyroxine metabolism can manifest in a similar fashion. Nephrotic syndrome is a rare cause of such a presentation though its presence can rapidly be suspected by dipstick urine testing. In this report we describe a patient with long-standing primary thyroid failure whose thyroxine dose requirements increased upon development of massive proteinuria. Biochemical testing and renal biopsy subsequently demonstrated nephrotic syndrome and amyloid deposition in association with myeloma. Dipstick urine testing should be considered in all hypothyroid patients with rising TSH levels, where good compliance with thyroxine therapy is likely.

Amyloidosis↗