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Biomedical subjects

J C Stevenson

Publications and source records attributed to J C Stevenson.

At least 181 records · Page 10Linked to original sources

Effect of rifampicin and isoniazid on vitamin D metabolism.

Rifampicin, 600 mg, and isoniazid, 300 mg daily for 14 days, reduced circulating levels of 25-hydroxy vitamin D (25-OHD) and 1 alpha, 25-dihydroxy vitamin D (1,25(OH)2D) by 34% (P less than 0.01) and 23% (P less than 0.05) in eight healthy subjects. This was accompanied by a rise in parathyroid hormone (PTH) of 57% (P less than 0.01), but not by a fall in serum calcium or phosphate levels. There was induction of endogenous cortisol oxidation in all subjects, but only in four fast acetylators was there a concomitant increase in antipyrine elimination. In the four slow acetylators antipyrine metabolism was inhibited after the first dose of the drugs. In nine tuberculous patients followed serially there was a fall in 25-OHD and 1,25 (OD)2D and a rise in PTH at the end of 1 mo (P less than 0.05). After 6 mo therapy 25-OHD concentration was further reduced (P less than 0.01), but there was no significant change in 1,25 (OH)2D or PTH levels. Combination treatment with rifampicin and isoniazid perturbs vitamin D metabolism, but less than might have been predicted from reports on each drug given alone. Nevertheless, tuberculous patients with already compromised calcium homeostasis receiving this combination of drugs should be carefully monitored.

Adult↗

Bombesin: action on gut hormones and calcium in man.

Bombesin, a peptide with widespread biological actions, has been demonstrated in human tissues by immunological methods. To investigate its effect in man, synthetic bombesin was infused at low doses in six male volunteers. Bombesin at 2.4 pmol kg-1 min-1 produced significant rises in plasma insulin, glucagon, pancreatic polypeptide, gastrin, cholecystokinin, motilin, glucose-dependent insulinotropic polypeptide, neurotensin, enteroglucagon, vasoactive intestinal polypeptide, and serum calcium. In contrast, bombesin caused a profound fall in parathyroid hormone levels and reduced plasma glucose concentrations. A late rise in plasma calcitonin was also observed. Bombesin had no significant effect on the pituitary hormones, TSH, GH, PRL, or cortisol. No hormonal changes or alterations in calcium were noted during saline infusions. Bombesin has a marked stimulatory effect on gastrointestinal hormones, which is unique and opposite to the effect of somatostatin, a potent inhibitor of gut hormone release. Bombesin also influences calcium-regulating hormones, either directly or through its action on gut hormones. The bombesin concentrations achieved with the dosages used were low enough to indicate a possible physiological role for the endogenous peptide.

Adult↗

Interrelations of calcium-regulating hormones during normal pregnancy.

Profound changes in calcium metabolism occur during pregnancy. The mother has to make available extra calcium for fetal requirements while ensuring that her plasma and bone calcium concentrations are satisfactorily maintained. In a cross-sectional study plasma concentrations of the major calcium-regulating hormones--namely, calcitonin, parathyroid hormone, 25-hydroxyvitamin D (25-OHD), and 1,25-dihydroxyvitamin D (1,25-(OH)2D)--were measured to establish their interrelations during normal pregnancy. The major changes observed were increases in the circulating concentrations of 1,25-(OH)2D and calcitonin. Concentrations of parathyroid hormone and 25-OHD remained within the normal range. The increased concentrations of 1,25-(OH)2D enable the increased physiological need for calcium to be met by enhancing intestinal absorption of this element. The simultaneous rise in calcitonin opposes the bone-resorbing activities of 1,25-(OH)2D, thereby protecting the integrity of the maternal skeleton. Maternal calcium homeostasis is thus maintained yet the requirements of the fetus are fulfilled.

25-Hydroxyvitamin D 2↗

Calcitonin and the calcium-regulating hormones in postmenopausal women: effect of oestrogens.

In man, the major function of calcitonin appears to be prevention of excessive or unwanted bone resorption. There is a striking sex difference in circulating levels, with a relative deficiency in women. Calcitonin secretion in young adults is increased by oestrogens and therefore long periods of oestrogen lack, such as after the menopause, may be associated with a more pronounced calcitonin deficiency. This exaggerated deficiency could be an important factor in the pathogenesis of postmenopausal bone loss, especially since the latter may be due to excessive bone resorption. In a study of the effects of oestrogen treatment on circulating levels of calcitonin, parathyroid hormone, and vitamin-D metabolites in postmenopausal women, the most striking change was a sharp rise in plasma-calcitonin. Oestrogens prevent postmenopausal bone loss, and it is suggested that this effect could be mediated, at least in part, through control of calcitonin secretion. Calcitonin may prove effective in the prevention of postmenopausal bone loss, and it is suggested that this effect could be mediated, at least in part, through control of calcitonin secretion. Calcitonin may prove effective in the prevention of postmenopausal bone loss. Its place in the treatment of postmenopausal osteoporosis warrants further evaluation.

Aged↗

Stimulation of 1,25-dihydroxycholecalciferol production by prolactin and related peptides in intact renal cell preparations in vitro.

Ovine prolactin stimulated the 1 alpha-hydroxylase activity in isolated renal tubules and especially in primary kidney cell cultures, both prepared from vitamin D-deficient chicks. In primary chick kidney cell cultures, treated for 48 h with 1,25-dihydroxycholecalciferol (to induce the 24-hydroxylase activity) ovine prolactin, after a 1 h incubation period, stimulated the 1 alpha-hydroxylase activity without affecting the 24-hydroxylase activity. Similar results were obtained with related peptide hormones such as human growth hormone, chicken growth hormone, and human placental lactogen. These observations are discussed in relation to the possible role of these peptide hormones as modulators of 1,25-dihydroxycholecalciferol production in physiological situations of calcium stress, such as pregnancy, lactation, growth in mammals and egg laying in birds.

Animals↗

Sipple syndrome: marked variability of the disease within a family and implications for management.

Familial medullary carcinoma of the thyroid gland is often associated with phaeochromocytoma; this condition is known as Sipple syndrome. The rate of progression of the disease and the degree of malignancy of the medullary carcinoma may vary from family to family. Thus the nature and behaviour of this disease in any particular family influences the management of the thyroid carcinoma component. The authors measured plasma calcitonin and plasma catecholamines in 21 members of a family with Sipple syndrome. In one branch of this family 5 out of 7 members have so far been affected, 4 with metastases or recurrence of the carcinoma and 2 with development of phaeochromocytomas. In contrast, of the 14 members in the other 4 family branches, only 4 have had pathologically elevated plasma calcitonin concentrations following alcohol provocation, probably representing C-cell hyperplasia or very early neoplasia and apparently not progressing. None has evidence of phaeochromocytoma. This family demonstrates a striking variability in the natural history of Sipple syndrome which, despite increasing discovery of more families with medullary thyroid carcinoma, has not been previously reported. In the light of this finding, a reappraisal of the management of the thyroidal component of this disease is necessary. It appears that radical neck surgery may be needed to prevent recurrence of the disease.

Adrenal Gland Neoplasms↗

Pharmacology and therapeutic use of calcitonin.

Calcitonin is a peptide hormone secreted by the C-cells of the thyroid gland. A major physiological function of the hormone appears to be the protection of the skeleton against resorption in humans. It thus opposes the resorptive actions of parathyroid hormone and 1,25 dihydroxyvitamin D. This action is utilised pharmacologically in order to treat diseases where increased bone resorption is a major component. The efficacy of calcitonin in the treatment of Paget's disease of bone is well established, especially as it is currently the most effective agent in the treatment of the osteolytic form of the disease. In other bone diseases where resorption of bone is a component it is likely to be worthy of a trial of therapy. There are also sound theoretical reasons why calcitonin may be of benefit in the treatment of certain osteoporoses, especially in combination with other agents. Most recent studies would seem to support his view. A disadvantage of calcitonin therapy is that the hormone has to be administered parenterally, although future developments may obviate this. It is, however, a form of retreatment which is free of any long term serious side effects, and calcitonin now has a definite place in the management of specific bone and calcium disorders.

Animals↗

Effects in postmenopausal women of natural and synthetic estrogens on calcitonin and calcium-regulating hormone secretion. Relevance to postmenopausal osteoporosis.

The major function of calcitonin in man appears to be the prevention of excessive or unwanted bone resorption. There is a marked sex difference in circulating levels, with a relative deficiency in women. As calcitonin secretion in young women is known to be increased by estrogens, long periods of estrogen lack - such as the postmenopause - are possibly associated with a more pronounced calcitonin deficiency. This exaggerated deficiency could be an important factor in the pathogenesis of postmenopausal bone loss, especially as the latter is believed to be due to excessive bone resorption. We have studied the effects of three exogenous estrogens on the circulating levels in postmenopausal women of calcitonin, parathyroid hormone, the vitamin D metabolites 1,25 dihydroxyvitamin D and 25 hydroxyvitamin D, and calcium and phosphate. The most striking finding was a sharp rise in the plasma levels of calcitonin. Estrogens are known to prevent postmenopausal bone loss but the mechanism of action remains obscure. We suggest that the beneficial effects of estrogens could be mediated, at least in part, through control of calcitonin secretion. Thus calcitonin may prove effective in the prevention of postmenopausal bone loss and its role in the treatment of established osteoporosis warrants further evaluation.

Adult↗

Chemistry, physiology, and therapeutic applications of calcitonin.

The chemistry and physiology of calcitonin are reviewed with particular emphasis on the evolution of the hormone and its modern role in humans. It seems likely that the relative deficiency of calcitonin in women may be important in postmenopausal bone loss. A major therapeutic application of calcitonin is in the treatment of Paget's disease of bone, and current recommendations for therapy are presented.

Aging↗