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Biomedical subjects

I M Anderson

Publications and source records attributed to I M Anderson.

At least 19 recordsLinked to original sources

Effect of pindolol on endocrine and temperature responses to buspirone in healthy volunteers.

Ten healthy subjects received buspirone (30 mg orally) with and without pre-treatment with the 5-HT1A receptor antagonist, pindolol (80 mg over 3 days). Following pindolol treatment the growth hormone and hypothermic responses to buspirone were significantly decreased. There was also a delay in the onset of the prolactin response to buspirone but the total amount of prolactin secretion, calculated as area under the curve, was not significantly reduced. The data suggest that the growth hormone and hypothermic responses to buspirone in humans are mediated by 5-HT1A receptors, but an explanation founded on pharmacokinetic factors cannot presently be excluded. Both this latter possibility and the lack of selectivity of pindolol for 5-HT receptors indicate the need for the further neuroendocrine studies of the mode of action of buspirone, preferably with more selective 5-HT1A receptor antagonists.

Adult

Decreased 5-HT-mediated prolactin release in major depression.

The prolactin response to intravenous clomipramine, a 5-HT uptake inhibitor, was significantly attenuated in 12 patients with major depression. In contrast, in a further 12 depressed patients, the PRL responses to thyrotropin-releasing hormone, which acts directly on the pituitary to release PRL, were not reduced. These findings suggest that the reduction in 5-HT-mediated PRL release seen in depressed patients is due to an impairment of brain 5-HT function rather than a pituitary abnormality.

Adult

The effects of gepirone on neuroendocrine function and temperature in humans.

The effects of the selective 5-HT1A receptor agonist gepirone (10 and 20 mg orally) on neuroendocrine function and temperature were assessed using a single-blind cross-over design in 12 healthy male volunteers. Gepirone significantly increased plasma levels of ACTH, beta-endorphin, cortisol, prolactin and growth hormone. Following gepirone there was a significant decrease in body temperature and moderate increases in subjective reports of light-headedness, nausea and drowsiness. Our results are consistent with studies in rodents suggesting that 5-HT1A receptor agonists increase ACTH and prolactin secretion and decrease body temperature. Further investigations are needed to determine if the neuroendocrine and temperature effects of gepirone in humans are mediated by 5-HT1A receptors.

Adrenocorticotropic Hormone

Metergoline abolishes the prolactin response to buspirone.

Pretreatment of nine healthy subjects with the non-selective 5-HT receptor antagonist, metergoline (4 mg), abolished the increase in plasma prolactin produced by the anxiolytic drug, buspirone (15 mg). While these findings are consistent with a role for 5-HT receptors in the stimulatory effect of buspirone on plasma prolactin, a dopaminergic mechanism cannot be excluded by the present data.

Adult

Decreased plasma tryptophan concentration in major depression: relationship to melancholia and weight loss.

Plasma total tryptophan (TRP) concentration was significantly lower in 31 patients with major depression compared to a healthy control group. The ratio of plasma TRP concentration to that of other branch chain amino acids (the TRP:BCAA ratio) was also decreased. Further analysis revealed that the decrease in plasma TRP and TRP:BCAA ratio was most apparent in patients with major depression and melancholia. Overall, women but not men had significantly decreased plasma tryptophan concentrations, perhaps because of a contributory effect of weight loss; this latter effect, however, could not be distinguished clearly from a diagnosis of melancholia. Our data suggest that in some depressed patients, reductions in plasma tryptophan availability may contribute to abnormalities in brain 5-hydroxytryptamine function.

Adult

Dieting reduces plasma tryptophan and alters brain 5-HT function in women.

A three week low calorie diet significantly reduced both total plasma tryptophan and the ratio of tryptophan to competing amino acids in a group of 15 healthy volunteers. Despite a similar percentage weight loss the reduction in plasma tryptophan was greater in women than men. In addition, only in women was dieting associated with increased prolactin secretion following intravenous tryptophan, a measure of brain 5-hydroxytryptamine (5-HT) function. These results suggest that dieting reduces the availability of circulating tryptophan for brain 5-HT synthesis. Women appear more vulnerable than men both to this effect and to its consequences for brain 5-HT function. Altered brain 5-HT function may play a part in some of the psychological consequences of dieting, including the development of clinical eating disorders.

Adult

Neuroendocrine effects of azapirones.

In healthy volunteers, the azapirones--buspirone, ipsapirone, and gepirone--increase plasma cortisol and decrease body temperature; buspirone and gepirone also increase plasma prolactin and growth hormone. Data from animal studies suggest that the ability of azapirones to decrease body temperature and increase corticotropin and corticosterone is mediated by stimulation of presynaptic and postsynaptic serotonin (5-hydroxytryptamine, 5-HT) type 1A subtype receptors, respectively. The mechanism of altered growth hormone and prolactin secretion is less clear. While animal studies implicate changes in dopamine function, current human investigations suggest that 5-HT1A receptors also may be involved in these endocrine responses. Further investigations, using more selective 5-HT receptor antagonists, will be required to resolve this issue.

Animals

Endocrinological responses to 5-HT.

There is increasing evidence that neuroendocrine and temperature responses in humans can be employed to study the functional sensitivity of different 5-HT receptor subtypes. The evidence suggests that the PRL response to LTP is mediated by 5-HT1 receptors, perhaps the 5-HT1A subtype, though further studies are needed to confirm this effect. It is uncertain whether the PRL responses to other 'presynaptic' challenges of 5-HT function, for example, fenfluramine, are mediated by the same post-synaptic 5-HT receptor subtype as that for LTP. Conversely it seems likely that agonists which stimulate 5-HT2/1C receptors increase both plasma PRL and ACTH in humans. There is also evidence that 5-HT1A receptors can increase ACTH secretion. This suggests that in humans as in animals both the 5-HT1A and 5HT2/1C receptors can facilitate ACTH release, though the significance of this dual control is not understood. It is also possible that both 5-HT1A and 5-HT2/1C receptors stimulate PRL release, but 5-HT1A receptors may have a more prominent role in GH secretion. In both human and animal studies 5-HT1A and 5-HT2 receptor agonists may produce opposite effects on body temperature. These recent developments in 5-HT neuroendocrinology have been of great interest, but much is still uncertain. Progress in this field will be considerably advanced by the availability of new selective 5-HT receptor ligands, particularly selective receptor antagonists.

Animals

Effect of moderate weight loss on prolactin secretion in normal female volunteers.

Sleep-related prolactin secretion and prolactin responses to the infusion of low doses of the dopamine antagonist, metoclopramide, and thyrotropin-releasing hormone were measured in 11 female volunteers before and after undertaking a diet in which they lost a mean of 3.1 kg in weight in 3 weeks. No effect of weight loss on these measures was found, but there was a significant, although modest, reduction in fasting plasma tryptophan concentration without any change in the concentration of competing amino acids.

Adult

Clomipramine enhances prolactin and growth hormone responses to L-tryptophan.

The effects of the 5-hydroxytryptamine (5-HT) uptake inhibitor clomipramine on the prolactin (PRL) and growth hormone (GH) responses to L-tryptophan (LTP) were assessed in six normal subjects. Oral administration of 20 mg clomipramine 2 h prior to LTP infusion (50 mg/kg) significantly enhanced both endocrine responses, suggesting that the increases in plasma PRL and GH produced by LTP are mediated by 5-HT pathways. These findings, taken together with previous observations that 5-HT2 receptor antagonists do not attenuate the PRL response to LTP, suggest that the 5-HT-induced release of PRL in man may be mediated by 5-HT1 receptors.

Adult

Exacerbations of chronic bronchitis: exogenous or endogenous infection?

Six male patients with chronic bronchitis, who were known previously to have excreted Streptococcus pneumoniae and/or Haemophilus influenzae, both at the times of exacerbations and during remission, were studied for 43 to 52 months. Sputum was examined fortnightly and at the time of exacerbations. Strains of Strep. pneumoniae were serotyped and those of Haemophilus species were typed by antibiograms along with other supporting methods. Sera collected before or at the time of an exacerbation and seven and 30 days afterwards were examined by complement fixation tests against respiratory viruses and Mycoplasma pneumoniae. In 18 out of 25 exacerbations there was evidence of a new type of Strep. pneumoniae and/or Haemophilus spp. or of a current virus infection, suggesting exogenous infection in the majority of these cases. There was a possible reason for failure to detect a new pathogen in three of the seven cases in which none was found. In five further exacerbations adequate investigation was not possible.

Aged

The elective treatment of graft-versus-host disease following a bone marrow graft from a father to a son with severe combined immunodeficiency.

The details of the first successful bone marrow graft from father to son are described. The recipient developed an acute graft-versus-host reaction on the seventh day which was successfully treated with anit-lymphocyte globulin and methotrexate. This regime did not destroy the graft and the child is alive and well with normal immunological function some 2 1/2 years later.

Antilymphocyte Serum