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Biomedical subjects

M F Scanlon

Publications and source records attributed to M F Scanlon.

At least 91 records · Page 5Linked to original sources
PubMed1991

Cholinergic blockade with pirenzepine induces dose-related reduction in glucose and insulin responses to a mixed meal in normal subjects and non-insulin dependent diabetics.

OBJECTIVE: The aim of the study was to assess the effects of cholinergic blockade with pirenzepine on glucose and insulin responses to a mixed meal in normal subjects and patients with non-insulin dependent diabetes (NIDDM). Further, to assess in normal subjects the relative importance of nocturnal GH suppression by pirenzepine. DESIGN: Placebo, 100 or 200 mg pirenzepine were given to the normal subjects 1 hour before a standard mixed meal. The effects of placebo or 200 mg pirenzepine at night on nocturnal GH secretion and subsequent breakfast carbohydrate tolerance were also studied. NIDDMs were given placebo or 200 mg pirenzepine before the meal. SUBJECTS: We studied six healthy male volunteers (ages 20-22, body mass indices 20.3-23.3) and ten NIDDMs (eight men, ages 42-74); five obese (BMI 25.5-31.8) and five non-obese (BMI 21.2-24.8). MEASUREMENTS: Serial plasma glucose and insulin concentrations were measured for 3 hours after a standard mixed meal. RESULTS: Acute pretreatment of normal male volunteers with pirenzepine produced a dose-related improvement in carbohydrate tolerance. Peak post-prandial plasma glucose levels were delayed and significantly reduced following 200 mg orally (6.5 +/- 0.1 mmol/l), but not following 100 mg (7.3 +/- 0.3), compared with placebo (7.6 +/- 0.3). Peak insulin levels were similarly delayed and reduced by the 200 mg dose only (36.5 +/- 6.1 mU/l, compared with 49.8 +/- 8.7). Suppression of nocturnal GH by 200 mg pirenzepine at night produced a small reduction in fasting plasma glucose (5.0 +/- 0.1 mmol/l, compared with 5.3 +/- 0.1, P less than 0.02) but did not improve subsequent breakfast carbohydrate tolerance. Peak plasma glucose in NIDDMs was reduced following pirenzepine (12.4 +/- 0.9 mmol/l) compared with placebo (14.3 +/- 1.0, P less than 0.01). This reduction was equally significant in obese and non-obese groups. Peak plasma insulin was also reduced by pirenzepine (22.4 +/- 3.9 mU/l) compared with placebo (42.4 +/- 5.3, P less than 0.01). Insulin suppression was quantitatively greater in obese than in non-obese patients. CONCLUSIONS: Improvement in carbohydrate tolerance after pirenzepine in normal subjects is dose related and largely independent of GH suppression. Cholinergic blockade can also improve meal carbohydrate tolerance with simultaneous reduction in plasma insulin concentrations in non-insulin dependent diabetics, particularly those with obesity.

Adult↗
PubMed1991

Effect of pyridostigmine and pirenzepine on GH responses to GHRH in hyperthyroid patients.

OBJECTIVE: We wished to investigate whether thyrotoxicosis can influence the cholinergic modulation of GH secretion. DESIGN: Pyridostigmine was given orally, then GHRH injected i.v., and levels were measured. In a separate study, pirenzepine was injected i.v., then GHRH, and growth hormone levels were measured. PATIENTS: Thyrotoxic patients were compared with normal subjects. MEASUREMENTS: GH was measured from -30 to +120 minutes at intervals of 15 minutes. RESULTS: Pyridostigmine markedly increased GH responses to GHRH in normal subjects, but not in thyrotoxic patients. Pirenzepine abolished the GH response to GHRH in thyrotoxic patients. CONCLUSIONS: GH responses to GHRH in hyperthyroid patients were suppressed by cholinergic muscarinic receptor blockade with pirenzepine. Activation of cholinergic pathways with pyridostigmine did not increase GH responses to GHRH in these patients. This may be a consequence of increased hypothalamic cholinergic function or reduced hypothalamic GHRH activity in hyperthyroidism. Our findings demonstrate a further mechanism by means of which thyroid status may affect the secretory activity of the somatotroph.

Adolescent↗
PubMed1991

Non-secretory adenomas of the pituitary treated by trans-ethmoidal sellotomy.

A consecutive series of 35 clinically non-secretory pituitary adenomas treated surgically by the transethmodial approach is presented. Mean age at presentation was 60 years, with a male-to-female ratio of 2:1. These tumours present later than hormone secreting tumours: 90% were over 2 cm in diameter at operation. Seventy-one per cent of patients had impaired vision and 89% had hypopituitarism. Surgical treatment relieved or significantly improved visual fields in 79% of patients with impaired vision. Ninety-one per cent required permanent hormone replacement. Mean follow-up was for 4.4 years. Five tumours recurred, causing recurrent visual symptoms. No tumours recurred in those patients treated with postoperative radiotherapy, but follow-up in this group was only for a mean of 2.7 years.

Adenoma↗
PubMed1991

Preliminary characterization of growth factors secreted by human pituitary tumors.

To investigate the secretion of mitogenic factors by human pituitary tumors we have cultured cells from 54 adenomas in serum-free medium. Conditioned media from 28 (52%) elicited dose-dependent stimulation of [3H]thymidine incorporation into rat GH3 cells (22-338% above control), while 14 (26%) inhibited GH3 proliferation. Stimulating activity was observed more frequently in nonfunctional tumor-conditioned medium (73%; n = 22) than in secretory tumor-conditioned medium (37%; n = 32). Of 10 tumour-conditioned media with mitogenic activity for GH3 cells, only 4 produced modest stimulation of HEp2 (human laryngeal carcinoma) cells. In contrast, [3H]thymidine incorporation into A431 (human squamous carcinoma) and PC12 (rat adrenal pheochromocytoma) cells was enhanced by each of 15 tumor-conditioned media (up to 342% and 275%, respectively), 8 of which had shown stimulatory and 2 inhibitory effects on GH3 cells. Gel filtration of pooled conditioned media from 10 nonfunctional tumors showed significant growth-promoting activity for GH3 cells in fractions corresponding to mol wt of 2-3 and 11-18 kDa. Proliferative activity on A431 cells also eluted in two positions; one corresponded to the higher mol wt peak seen with GH3 cells, while the other, not observed with GH3 cells, was in the 3- to 6-kDa range. These findings suggest that cells derived from human pituitary adenoma tissue synthesize and secrete several growth factors, each of which may have its own target cell specificities. These factors have yet to be characterized, but we suggest that they may have a role in stimulating the development or maintenance of human pituitary adenomas.

Adenoma↗
PubMed1990

Motor neurone disease serum and beta-N-methylamino-L-alanine stimulate thyrotrophin-releasing hormone production by cultured brain cells.

We have investigated the effects of serum from patients with motor neurone disease (MND) and of the plant-derived excitotoxin beta-N-methylamino-L-alanine (L-BMAA) on thyrotrophin-releasing hormone (TRH) and somatostatin (SS) production by fetal rat brainstem cell cultures. Compared to age- and sex-matched normal and neurological disease control sera, MND sera produce a 2- to 3-fold increase in TRH content of the cultures with no change in SS levels. L-BMAA produced similar dose-related and stereospecific effects on the cultures increasing TRH levels to 2-fold with no effect on SS levels. These findings may be relevant to the understanding of the aetiology of MND.

Aged↗
PubMed1990

Occurrence of galanin-like immunoreactivity in growth hormone-releasing factor (GRF)-containing neurons of the monkey (Macaca fascicularis) infundibular nucleus and median eminence.

The distribution of growth hormone-releasing factor (GRF)- and galanin (GAL)-immunoreactive (-IR) neurons in the mediobasal hypothalamus of the monkey (Macaca fascicularis) was studied with immunohistochemistry using a direct double-labelling method. GRF- and GAL-IR cell bodies were demonstrated in the ventral part of the infundibular nucleus and dense aggregations of GRF- and GAL-IR fibers were seen in the external layer of the median eminence, closely surrounding portal vessels. Double-staining revealed that GRF and GAL were colocalized in cell bodies of the infundibular nucleus and in nerve fiber varicosities in the external layer of the median eminence. GAL has been reported to stimulate the secretion of growth hormone in both rats and humans, most likely via hypothalamic mechanism(s).

Animals↗
PubMed1990

A clinical update on hypothalamic-pituitary control.

There is at present an accumulation of data which indicate the importance of stimulatory and inhibitory growth factors in the paracrine, and perhaps autocrine, regulation of anterior pituitary cell growth and function. There may well be several more specific pituitary growth factors which will be identified in the near future. Preliminary data are also emerging concerning the pattern of oncogene expression in human pituitary tumours. It is now necessary to relate growth factor production, oncogene expression and hypothalamic regulation to specific anterior pituitary cell populations and human pituitary adenomas. In the midst of these studies it should not be forgotten that coordinated vascular and supporting tissue growth is also crucial to the normal development and maintenance of anterior pituitary structure and function.

Adrenocorticotropic Hormone↗
PubMed1990

Differences in clinical and endocrine features between obese and non-obese subjects with polycystic ovary syndrome: an analysis of 263 consecutive cases.

Two hundred and sixty-three women with ultrasound-diagnosed polycystic ovary syndrome were studied of whom 91 (35%) were obese (BMI greater than 25 kg/m2). Obese women with PCOS had a greater prevalence of hirsutism (73% compared with 56%) and menstrual disorders than non-obese subjects. Total testosterone and androstenedione concentrations in serum were similar in the two subgroups but SHBG concentrations were significantly lower, and free testosterone levels higher, in obese compared with lean subjects. In addition, concentrations of androsterone glucuronide, a marker of peripheral 5 alpha-reductase activity, were higher in obese than in non-obese women with PCOS. There were no significant correlations of either SHBG or free testosterone with androsterone glucuronide suggesting that obesity has independent effects on transport and on metabolism of androgen. There were no significant differences between the subgroups in either baseline gonadotrophin concentrations or the pulsatile pattern of LH and FSH secretion studied over an 8-h period. There was, however, an inverse correlation of FSH with BMI, but only in the obese subgroup. In conclusion, the increased frequency of hirsutism in obese compared with lean women with PCOS is associated with increased bio-availability of androgens to peripheral tissues and enhanced activity of 5 alpha-reductase in obese subjects. The mechanism underlying the higher prevalence of anovulation in obese women remains unexplained.

Androgens↗
PubMed1990

Effect of oral glucose on the late growth hormone rise and growth hormone responses to GHRH in normal subjects.

A late rise in serum GH occurs 3-5 h following oral glucose in man. In order to investigate the mechanisms through which this occurs we have studied the late GH rise after oral glucose during administration of a supramaximal dose of GHRH. In eight normal subjects, oral glucose (100 g) greatly enhanced the GH responses to a supramaximal dose of GHRH (50 micrograms bolus, followed immediately by 100 micrograms/h infusion for 3 h) given 3.5 h after the glucose. GH peak (mean +/- SEM) elicited by GHRH (bolus + infusion) rose from 55.2 +/- 20.4 to 133.4 +/- 29.6 mU/l (P less than 0.02) after glucose pretreatment. In conclusion, it is likely that the late rise in GH secretion induced by oral glucose occurs via a non-GHRH-dependent mechanism. These data are consistent with the hypothesis that the delayed GH response to glucose is a consequence of reduced release of somatostatin from the hypothalamus.

Administration, Oral↗
PubMed1990

Long-term treatment of acromegaly with a long-acting analogue of somatostatin, octreotide.

We have treated 16 acromegalic patients for up to 44 months with octreotide in varying doses. Growth hormone levels were suppressed in 14 patients with associated clinical improvement. IGF-1 levels were measured in 12 and fell into the normal range in 10. Prolactin was suppressed in six hyperprolactinaemic patients but was unaltered in normoprolactinaemic acromegalic patients. Post-prandial hyperglycaemia with impaired insulin secretion was noted in all patients, and one patient required oral hypoglycaemic agents. Octreotide did not affect thyroid function. CT scans from before and after six months of treatment demonstrated minimal tumour shrinkage in only two patients. Octreotide was well tolerated with no serious haematological or biochemical disturbance and no evidence of malabsorption. Two patients developed gallstones. Octreotide is effective in acromegaly. The development of gallstones is the only serious adverse event we have encountered.

Acromegaly↗
PubMed1989

Thyroid function tests in elderly patients with and without an acute illness.

Thyroid function was assessed by measurement of free thyroid hormones and thyrotrophin (TSH) in 78 acutely ill elderly patients and in a control group without acute illness. Abnormal results with any test were more frequently found in the acutely ill group than in controls. In particular, abnormal TSH values were found in 40% of the acutely ill group and in only 8% of controls (p less than 0.001). Seven acutely ill subjects had very low TSH levels (less than 0.04 mU/l) and a blunted response to thyroid-releasing hormone (TRH). With few exceptions these abnormalities could not be attributed to thyroid disease. This suggests that pituitary TSH secretion can be impaired in euthyroid sick old people. High sensitivity TSH assays may therefore be inappropriate as first-line tests of thyroid function, at least in this select group.

Acute Disease↗
PubMed1989

Cholinergic blockade with pirenzepine improves carbohydrate tolerance and abolishes the GH response to meals in normal subjects.

Pretreatment of normal male volunteers with the cholinergic muscarinic receptor-blocking drug pirenzepine (200 mg p.o.) abolishes the delayed GH response to a meal stimulus. In addition, the glycaemic and insulin responses to meals are significantly reduced following this dose of pirenzepine. The data suggest that the effect of pirenzepine on the glucose response to meals is at least partly independent of the inhibition of GH release. Our findings are of relevance to the further investigation of cholinergic muscarinic antagonist in diabetes mellitus.

Adult↗
PubMed1989

Early morning hyperglycemia in insulin-dependent diabetes: acute and sustained effects of cholinergic blockade.

Nocturnal release of GH has been shown to be related to the early morning rise in plasma glucose (PG) seen in insulin-dependent diabetes mellitus (IDDM). We have studied the effects of suppression of nocturnal GH release during a single night (acute study) and after nightly suppression for 1 week (chronic study). Changes in plasma glucose and counter-regulatory hormone concentrations were monitored in six IDDM patients during a constant overnight insulin infusion alone, after addition of the anticholinergic agent pirenzepine to cause acute GH suppression, and again on the seventh night of such treatment. In control experiments (infusion of insulin alone; 0.075 mU/kg.min) PG increased from (mean +/- SEM) 5.6 +/- 0.6 mmol/L at 2400 h to 11.1 +/- 1.3 mmol/L at 0900 h (P = 0.0024). Addition of pirenzepine (100 mg at 2200 h and again at 2400 h) in the acute study resulted in a PG change from 5.6 +/- 0.3 mmol/L at 2400 h to 8.4 +/- 1.4 mmol/L at 0900 h (P = 0.17). After pirenzepine administration at the same dose for 7 nights, PG increased from 4.7 +/- 0.6 mmol/L at 2400 h to 6.8 +/- 1.2 mmol/L at 0900 h (P = 0.11). Increases in PG during the study period were significantly less after chronic treatment than after acute treatment compared with changes on control nights. The nocturnal release of GH, which was demonstrated in all patients during the control nights, was suppressed in all patients during the acute study and in four of six patients during the chronic studies. We conclude that initial reduction of the early morning rise of PG in IDDM is associated with acute suppression of nocturnal GH release, and that the more significant sustained effect of anticholinergic GH suppression on the rise of PG may be associated with additional indirect effects on insulin clearance.

Adult↗
PubMed1989

Effects of hypothyroidism, tri-iodothyronine and glucocorticoids on growth hormone responses to growth hormone-releasing hormone and His-D-Trp-Ala-Trp-D-Phe-Lys-NH2.

The aim of this study was to investigate the role of thyroid hormones and glucocorticoids on GH secretion. Secretion of GH in response to GH-releasing hormone (GHRH) (5 micrograms/kg) was markedly (P less than 0.001) decreased in hypothyroid rats in vivo (peak GH responses to GHRH, 635 +/- 88 micrograms/l in euthyroid rats vs 46 +/- 15 micrograms/l in hypothyroid rats). Following treatment with tri-iodothyronine (T3; 20 micrograms/day s.c. daily for 2 weeks) or cortisol (100 micrograms/day s.c. for 2 weeks) or T3 plus cortisol, a marked (P less than 0.01) increase in GH responses to GHRH was observed in hypothyroid rats (peak GH responses, 326 +/- 29 micrograms/l after T3 vs 133 +/- 19 micrograms/l after cortisol vs 283 +/- 35 micrograms/l after cortisol plus T3). In contrast, none of these treatments modified GH responses to GHRH in euthyroid animals. Hypothyroidism was also associated with impaired GH responses to the GH secretagogue, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6). Secretion of GH in response to GHRP-6 in vivo was reduced (P less than 0.01) in hypothyroid rats (peak GH responses, 508 +/- 177 micrograms/l in euthyroid rats vs 203 +/- 15 micrograms/l in hypothyroid rats). In-vitro studies carried out using monolayer cultures of rat anterior pituitary cells derived from euthyroid and hypothyroid rats showed a marked impairment of somatotroph responsiveness to both GHRP-6 and somatostatin in cultures derived from hypothyroid rats. In summary, our data suggest that thyroid hormones and glucocorticoids influence GH secretion by modulating somatotroph responsiveness to different GH secretagogues.

Animals↗
PubMed1988

Alpha-2-adrenergic pathways release growth hormone via a non-GRF-dependent mechanism in normal human subjects.

Administration of a supramaximal dose of GRF 1-44 (200 micrograms, i.v.) to normal human volunteers increased GH levels while a further bolus of GRF (200 micrograms i.v.) given 2 hours later failed to increase plasma GH levels. In contrast, alpha-adrenergic receptor agonism with either propranolol-adrenaline infusion or clonidine increased plasma GH levels at a time when GH responses to this supramaximal dose of GRF were absent. This indicates that alpha-adrenergic pathways stimulate GH secretion through a non-GRF-dependent mechanism in normal human subjects.

Adult↗
PubMed1988

Growth hormone (GH) responses to arginine and L-dopa alone and after GHRH pretreatment.

In order to investigate the mechanisms by which arginine and L-dopa cause GH release in humans we measured the GH response to GHRH 1-44 (200 micrograms i.v.), arginine (30 g i.v. over 30 min) and L-dopa (500 mg orally) administered alone and 120 minutes following pretreatment with GHRH 1-44 (200 micrograms i.v.) in normal male subjects. Prior GHRH administration abolished the GH response to subsequent GHRH. Arginine infusion induced a rise in GH levels maximal at 45 min. Following GHRH pretreatment the GH response to arginine was enhanced, with peak values of 19.3 +/- 6.4 vs 53.3 +/- 16.5 mU/l (mean +/- SEM) respectively (P less than 0.02). L-dopa alone induced a rise in GH levels maximal at 90 min (17.6 +/- 7.4 mU/l, mean +/- SEM) but this rise was abolished by pretreatment with GHRH.

Adult↗