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Biomedical subjects

S Thom

Publications and source records attributed to S Thom.

32 records · Page 2Linked to original sources

Cytomegalovirus colitis and oesophageal ulceration in the context of AIDS: clinical manifestations and preliminary report of treatment with Foscarnet (phosphonoformate).

Three patients with biopsy diagnosed invasive cytomegalovirus infection of the colon have been seen in the context of the acquired immune deficiency syndrome (AIDS). Cytomegalovirus colitis presented with fever, abdominal distention, bloody diarrhoea and weight loss. Plain abdominal radiographs showed generalised large bowel dilatation in one patient. Cytomegalovirus infection was shown histologically, but the virus could not be cultured from the stool; no other gastrointestinal pathogens could be demonstrated. The patients were treated with a 14 day continuous infusion of Foscarnet 0.08 mg/kg/min (phosphonoformate, Astra Pharmaceuticals). One patient showed a partial response to therapy, but the cytomegalovirus colitis relapsed; the second patient had a symptomatic response only and the third patient died of non-cytomegalovirus opportunist infection while on treatment. Two other patients with biopsy proven cytomegalovirus ulceration of the oesophagus were seen, presenting with dysphagia, fever and weight loss. Invasive infection of the gastrointestinal tract with cytomegalovirus is now a major clinical problem in AIDS. Treatment with Foscarnet may be initially effective, but does not eliminate cytomegalovirus infection.

Acquired Immunodeficiency Syndrome

The action of a dopamine (DA1) receptor agonist, fenoldopam in human vasculature in vivo and in vitro.

This study was designed to investigate dopaminergic mechanisms in human vasculature using the selective vascular dopamine receptor agonist fenoldopam in vivo and in vitro. In vivo, forearm blood flow was measured plethysmographically and in vitro isolated rings of human blood vessels from a variety of sites were used for tissue bath studies. Intra-arterial fenoldopam markedly increased forearm blood flow, this effect was antagonised by (R) sulpiride, a vascular dopamine (DA1) antagonist, but not by metoclopramide, a neuronal (DA2) antagonist, or by guanethidine, an adrenergic neurone blocking agent. In vitro, fenoldopam relaxed preconstricted human renal, mesenteric and lumbar arteries, but not saphenous vein in a concentration dependent manner. (RS) sulpiride and SCH 23390 competitively antagonised this effect. These studies demonstrate the presence of a vasodilatory vascular dopamine receptor in man both in vivo and in vitro.

Adolescent

Human vascular smooth muscle responses mediated by alpha 2 mechanisms in vivo and in vitro.

The effects of compounds with alpha 2-agonist and alpha 2-antagonist properties on human forearm blood flow and on isolated human arterial segments have been studied. The findings from these studies in vivo and in vitro did not provide evidence in support of the hypothesis that postsynaptic alpha 2-receptors mediate smooth muscle contraction in the tissues under investigation. The constriction of the forearm vascular bed in response to low intra-arterial doses of idazoxan (RX 781094), an alpha 2-antagonist, provides evidence for a physiological role for a presynaptic alpha 2 autoregulatory mechanism. The variability of the forearm vascular responses to higher doses of idazoxan highlights the pitfalls that may have misled previous authors in their interpretation of the results of similar studies. A U-shaped dose-response curve to compounds with mixed alpha 2- and alpha 1-antagonist properties may be constructed, which emphasizes the importance of the dose-dependent selectivity of these antagonists at alpha 2- and alpha 1-receptors. The effect of idazoxan on the responses of arterial segments in vitro to exogenous catecholamines was dependent on the integrity of the endothelium, and provides evidence that alpha 2-receptors may mediate release of the endothelium-derived relaxing factor.

Adrenergic alpha-Agonists

In vivo and in vitro studies of alpha 2-adrenoceptor responses in human vascular smooth muscle.

To assess the role of alpha 2-receptor mechanisms in the control of vascular tone in humans, the pharmacological activities of RX 781094, an alpha 2-antagonist, and UK 14304, an alpha 2-agonist, have been investigated with the additional use of an alpha 1-antagonist, doxazosin. The effects of these agents on human forearm blood flow have been studied. In addition, some preliminary observations on the effects of these alpha 2-selective agents on isolated human arterial segments have been made. The alpha 2 agonist, UK 14304, produced a dose-dependent reduction in forearm blood flow, but the antagonism of this response by both doxazosin and RX 781094 at a dose which must be regarded as nonselective casts doubt on the hypothesis that alpha 2-receptors may be located postsynaptically in human vascular smooth muscle. These observations may be explained by UK 14304 having partial alpha 1-agonist activity. RX 781094 infused at low doses produced a dose-dependent reduction in forearm blood flow, which is interpreted as evidence for a presynaptic alpha 2 autoregulatory mechanism in the vasculature. Observations on isolated arterial segments (mesenteric, renal, splenic, gastric, and brachial) obtained during surgical procedures and mounted under tension in tissue baths did not provide evidence for a postsynaptic alpha 2-receptor mediating vasoconstriction. In contrast, the potentiation of the adrenaline response in the presence of the alpha 2 antagonist, RX 781094, supports the possibility that, in humans, an extrajunctional alpha 2-receptor may serve as the adrenergic mechanism for the release of an endothelial derived relaxing factor.

Adult

Randomised double-blind cross-over trial of potassium on blood-pressure in normal subjects.

A randomised double-blind cross-over study of increased oral potassium 64 mmol a day versus placebo was conducted in 20 young healthy males on normal sodium unrestricted diet. A significantly greater proportion had lower systolic and diastolic blood-pressures on potassium than on placebo. The mean diastolic pressure was significantly lowered, by 2.4 mm Hg, during potassium supplementation. Change in diastolic pressure correlated negatively with change in 24-hour urinary potassium and positively which change in 24-hour urinary sodium/potassium ratio in individual subjects.

Administration, Oral

Selective inhibition by danazol of follicle stimulating hormone during the luteal phase.

In each of six healthy, normally menstruating women, serum oestradiol, progesterone, basal and post luteinizing hormone releasing hormone (LHRH) gonadotrophin measurements were made during the luteal phase of a normal cycle and in a subsequent cycle in which 800 mg of danazol was given daily from the fifth day after the presumptive date of ovulation. No differences in the serum oestradiol, progesterone, or basal gonadotrophin levels were detected, but there was a selective impairment of the follicle stimulating hormone response to LHRH. The implications of these findings are discussed.

Danazol