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Biomedical subjects

J M Connell

Publications and source records attributed to J M Connell.

At least 181 records · Page 10Linked to original sources
PubMed1985

Body composition, blood pressure and the renin-angiotensin system in acromegaly before and after treatment.

Serial measurements of exchangeable sodium (Nae), blood pressure, circulating concentrations of growth hormone and the components of the renin-angiotensin-aldosterone system were made in 39 acromegalic patients: 26 patients were studied before and after treatment. Mean Nae was considerably increased, frequently being greater than values found in Conn's syndrome. Nine of the 26 untreated patients were hypertensive (35%) and of these seven were female and over the age of 52 years. In the untreated patients, Nae was positively correlated with age, blood pressure and growth hormone log concentration: the strongest correlation between Nae and growth hormone was obtained when the duration of the acromegalic process was taken into account. Following treatment there was often considerable reduction in Nae and this correlated closely with the fall in growth hormone: the relation between the fall in Nae and fall in blood pressure was less marked. The sodium retaining properties of growth hormone may cause a rise of blood pressure in a susceptible minority of acromegalics.

Acromegaly↗
PubMed1984

Peroxidase activity in relation to iodide, 17 beta-oestradiol and thioureylene drug uptake in human polymorphoneutrophils.

In polymorphoneutrophils (PMNs) phagocytosis is accompanied by an increase in peroxidase activity. Accumulation of iodide, thioureylene antithyroid drugs and 17 beta-oestradiol also occurs during the process. There is no evidence of an active iodide transport system in the PMNs as pertechnetate is not concentrated and neither ouabain nor perchlorate abolishes iodide accumulation. The uptakes of 125I, [35S]PTU and [3H]-17 beta-oestradiol were compared in phagocytosing PMNs and the effects of various compounds examined. In addition, chemiluminescence generation from luminol by PMNs and by horseradish peroxidase was studied. This indicated that uptake of all three compounds could be associated with activation of the peroxidase system, and inhibition of this enzyme system caused a reduction in their accumulation.

Estradiol↗
PubMed1984

Changes in circulating thyroid hormones during short-term hepatic enzyme induction with carbamazepine.

The effect of short-term hepatic enzyme induction with carbamazepine (CBZ) on circulating thyroid hormone concentrations was studied in 10 healthy male subjects. CBZ 400 mg per day was given for 21 days in 6 subjects and for 14 days in a further 4. In the former group the effect of therapy on the pituitary/thyroid axis was also assessed by measuring thyroid stimulating hormone (TSH) response to thyrotrophin-releasing hormone. CBZ therapy resulted in induction of hepatic monooxygenase activity, evidenced by a fall in antipyrine half-life (11.1 +/- 0.7 to 7.6 +/- 0.7 h; p less than 0.001), and a rise in antipyrine clearance (0.72 +/- 0.06 to 0.98 +/- 0.1 ml min-1 kg-1; p less than 0.001). A significant fall in total serum thyroxine (T4) (81.9 +/- 2.9 to 75.1 +/- 2.9 nmol l-1), and triiodothyronine (T3); (1.59 +/- 0.07 to 1.37 +/- 0.05 nmol l-1) and free T4 (16.03 +/- 0.82 to 14.2 +/- 0.8 pmol l-1) was seen after CBZ therapy. (all p less than 0.05). No significant change in reverse T3 or thyroid binding globulin occurred. In the 6 subjects studied for 21 days, maximal changes were found following 14 days' treatment. Basal and stimulated TSH remained unaltered. These effects on circulating thyroid hormone concentrations are likely to be secondary to hepatic enzyme induction leading to accelerated nondeiodinative hepatic hormone disposal. The reason for the failure of pituitary TSH secretion to rise in response to the fall in circulating T4 and T3 is unclear but may have implications for chronic treatment with CBZ in epileptic patients.

Adult↗
PubMed1984

Effect of pretreatment with carbimazole on early outcome following radio-iodine (131I) therapy.

Of a group of 55 thyrotoxic patients given therapeutic radio-iodine (131I), 24 were made euthyroid with carbimazole before 131I: the remainder were given 131I alone. Carbimazole was discontinued 5 days before 131I was administered. By 3 months after 131I treatment there was a greater incidence of hypothyroidism in the group given 131I alone (42% vs 25%), but a lower incidence of persistent thyrotoxicosis (16% vs 46%), (P less than 0.05). One year after treatment a similar proportion of each group had persistent thyrotoxicosis (21% vs 23%), but there remained a lower incidence of hypothyroidism in the group pretreated with carbimazole (25% vs 45%). It is suggested that pretreatment with carbimazole reduces the degree of radiation induced thyroid damage.

Aged↗
PubMed1984

The effect of low-dose dopamine infusion on anterior pituitary hormone secretion in normal female subjects.

The effect of low-dose dopamine infusion on anterior pituitary hormone secretion in a group of seven healthy female subjects is reported. Subjects were infused with NaCl solution (154 mmol/l) (control) or dopamine (0.01 and 0.1 micrograms min-1 kg-1 for 120 min at each rate) on separate days in the early follicular phase of consecutive menstrual cycles. Serum prolactin decreased during infusion of dopamine at 0.01 micrograms min-1 kg-1 but a similar fall was found in the control group. When the rate of dopamine infusion was increased to 0.1 micrograms min-1 kg-1 a further substantial decrease in prolactin concentration occurred, whereas prolactin in the control group showed no change. At the end of the period of dopamine infusion at 0.1 micrograms min-1 kg-1 serum prolactin remained significantly (P less than 0.025) lower than in the control group (85 +/- 12 vs 180 +/- 21 m-units/1). No change in thyrotrophin (TSH), growth hormone (GH) or luteinizing hormone (LH) was seen during either rate of dopamine infusion compared with control. While dopamine infusion at 0.1 micrograms min-1 kg-1 caused significant inhibition of prolactin secretion in normal female subjects, other pituitary hormone secretion was not affected: it is suggested that under the conditions of this study dopamine in hypophysial portal blood is not of primary importance in the control of basal TSH, GH and LH release.

Adult↗
PubMed1984

Changes in circulating androgens during short term carbamazepine therapy.

Serum concentrations of testosterone, androstenedione, dehydroepiandrosterone sulphate (DHAS), sex hormone binding globulin (SHBG) and luteinising hormone (LH) were measured before, during and after 21 days treatment with carbamazepine (CBZ)400 mg daily in six healthy male subjects. Induction of hepatic microsomal enzyme activity was confirmed by an increase in antipyrine clearance (P less than 0.02) and a fall in circulating CBZ concentrations from the seventh to the fourteenth CBZ dose (P less than 0.05). Within 7 days of starting CBZ there was a rise in SHBG (P less than 0.05) and a fall in testosterone, free testosterone fraction, DHAS and androstenedione (P less than 0.05). Testosterone, free testosterone fraction and androstenedione levels rose towards baseline by the end of the treatment period while DHAS concentration remained low (P less than 0.05). The rise in SHBG and increased androgen catabolism is most likely to be secondary to induction of hepatic monooxygenase activity by CBZ. These changes may be implicated in the production of sexual dysfunction encountered in some epileptic patients on chronic anticonvulsant therapy.

Androgens↗
PubMed1983

Inhibition of prolactin secretion by low-dose dopamine infusion in patients with hyperprolactinaemia.

Dopamine inhibits the secretion of prolactin from the pituitary. We have examined the relation between plasma dopamine and serum prolactin in 12 patients with hyperprolactinaemia during the infusion of dopamine at low doses (0.01, 0.1 and 1 microgram/kg/min). Plasma dopamine levels were raised from less than 100 pg/ml at the lowest rate of infusion to more than 20 000 pg/ml at the highest. Suppression of prolactin secretion was seen in some patients even at the lowest rate of infusion (0.01 microgram/kg/min); marked suppression of prolactin secretion (60%; 17--83%) was found at the intermediate dose (0.1 microgram/kg/min) in 11 of the 12 subjects with little further decrease in serum prolactin (70%; 50--87%) in those in whom the rate of dopamine infusion was increased ten-fold. One patient with the highest serum prolactin (82 500 mu/l) showed no decrease in prolactin either at the lowest or intermediate rates of dopamine infusion. Serum prolactin levels returned to values similar to or greater than basal on cessation of dopamine infusion. Infusion of dopamine at doses much lower than previously used in man exposes the pituitary to a concentration of dopamine sufficient to suppress prolactin secretion. These observations have important implications in understanding the pathophysiology of prolactin secretion from the pituitary gland and for future investigations of the control of hormone release by dopamine.

Depression, Chemical↗
PubMed1983

Transient hypothyroidism following radioiodine therapy for thyrotoxicosis.

A prospective study of thyroid function including serial tracer radioisotope uptake measurements in 55 patients treated with 131I therapy is described. Five patients had an episode of transient hypothyroidism within eight months of treatment: in three of these patients this was due to impaired organification of iodide, with normal iodide trapping by the thyroid (as measured by a twenty minute 123I uptake) being preserved. In contrast, in all patients who developed permanent hypothyroidism, iodide trapping was markedly diminished and did not recover. It is suggested that hypothyroidism due to organification failure following 131I therapy is potentially short-lived; where hypothyroidism is associated with gross impairment of iodide trapping, recovery is unlikely. Early iodine uptake measurements may be of value in selecting those patients whose hypothyroidism is transient and who do not require permanent thyroid hormone replacement.

Female↗
PubMed1983

Accumulation of thiourylene antithyroid drugs in mouse salivary gland.

[35S]Methimazole and [35S]propylthiouracil were shown to accumulate in mouse submandibular gland in vivo, with maximal tissue: plasma ratios being achieved at the lowest dose of drug studied (0.1 microgram/animal). Autoradiography of submandibular glands showed that the drugs were localized to the intralobular ductal epithelium and within the lumen of the convoluted granular tubule, which was identical to the localization of radiolabelled iodide. Histochemical studies indicated that this was the site of peroxidase activity within the gland. Drug accumulation persisted when iodide trapping was competitively inhibited using perchlorate. These data suggest that antithyroid drug accumulation by this tissue is not dependent on the anion trap; the localization of drug and iodide at the site of peroxidase activity suggest that this may be an important factor in the mechanism of drug accumulation, possibly related to subsequent drug metabolism.

Animals↗
PubMed1983

Influence of sodium perchlorate on thiourylene antithyroid drug accumulation in mice.

Radiolabelled [35S]propylthiouracil and [35S]methimazole were shown to accumulate in mouse thyroid gland in vivo, with maximal tissue/plasma ratios and maximal intrathyroidal levels of 35S-labelled drug being seen at the lowest dose of drug studied (0.1 micrograms/animal). Pretreatment with sodium perchlorate (10 mg) abolished iodide trapping by the thyroid and caused a fall in accumulation of both [35S]methimazole and [35S]propylthiouracil, although this effect was not seen at higher doses of drug, when tissue/plasma ratios approached unity. These data suggest that thiourylene antithyroid drug accumulation by the thyroid gland does not depend directly on the anion trap, and it is suggested that this accumulation might depend on subsequent intrathyroidal drug metabolism.

Animals↗
PubMed1981

Long-term use of potassium perchlorate.

A case of Graves' disease with potassium perchorate for 22 years without ill effect is described. Thyrotoxicosis recurred 4 weeks after the medication was withdrawn, suggesting that euthyroidism had been maintained by chronic use of the drug. As toxicity of perchlorate is probably dose related, it is suggested that long-term use of low dose perchlorate may be no more hazardous than alternative antithyroid therapy.

Aged↗
PubMedDate not supplied

Insulin as a vascular hormone: implications for the pathophysiology of cardiovascular disease.

1. Metabolic disorders, such as obesity and non-insulin-dependent diabetes mellitus, and cardiovascular disorders, such as essential hypertension, congestive cardiac failure and atherosclerosis, have two features in common, namely relative resistance to insulin-mediated glucose uptake and vascular endothelial dysfunction. 2. Significant increases in limb blood flow occur in response to systemic hyperinsulinaemia, although there is marked variation in the results due to a number of confounding factors, including activation of the sympathetic nervous system. Local hyperinsulinaemia has a less marked vasodilator action despite similar plasma concentrations, but this can be augmented by co-infusing D-glucose. 3. Insulin may stimulate endothelial nitric oxide production or may act directly on vascular smooth muscle via stimulation of the Na+-H+ exchanger and Na+/K+-ATPase, leading to hyperpolarization of the cell membrane and consequent closure of voltage-gated Ca2+ channels. 4. There is evidence both for and against the existence of a functional relationship between insulin-mediated glucose uptake (insulin sensitivity) and insulin-mediated vasodilation (which can be regarded as a surrogate measure for endothelial function). 5. If substrate delivery is the rate-limiting step for insulin-mediated glucose uptake (in other words, if skeletal muscle blood flow is a determinant of glucose uptake), then endothelial dysfunction, resulting in a relative inability of mediators, including insulin, to stimulate muscle blood flow, may be the underlying mechanism accounting for the association of atherosclerosis and other cardiovascular disorders with insulin resistance. 6. Glucose uptake may determine peripheral blood flow via stimulation of ATP-dependent ion pumps with consequent vasorelaxation. 7. A 'third factor' may cause both insulin resistance and endothelial dysfunction in cardiovascular disease. Candidates include skeletal muscle fibre type and capillary density, distribution of adiposity and endogenous corticosteroid production. 8. A complex interaction between endothelial dysfunction, abnormal skeletal muscle blood flow and reduced insulin-mediated glucose uptake may be central to the link between insulin resistance, blood pressure, impaired glucose tolerance and the risk of cardiovascular disease. An understanding of the primary mechanisms resulting in these phenotypes may reveal new therapeutic targets in metabolic and cardiovascular disease.

Cardiovascular Diseases↗