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Biomedical subjects

M Davie

Publications and source records attributed to M Davie.

At least 19 recordsLinked to original sources
PubMed2000

Intermittent oral disodium pamidronate in established osteoporosis: a 2 year double-masked placebo-controlled study of efficacy and safety.

The effect of oral pamidronate on bone mineral density and its adverse effect profile was investigated by a double-masked placebo-controlled study of 122 patients aged 55-75 years with established vertebral osteoporosis. Patients on active therapy received disodium pamidronate 300 mg/day (group A) for 4 weeks every 16 weeks, 150 mg/day (group B) for 4 weeks every 8 weeks or placebo (group C). All patients additionally received 500 mg of calcium and 400 IU vitamin D daily. Dual-energy X-ray absorptiometry measurements of the spine, hip, forearm and total body were performed at baseline and 6-monthly for 2 years using a Hologic QDR 1000 device at two sites. Serum osteocalcin and urinary deoxypyridinoline were measured at the above visits and at 3 months. The percentage change (SEM) in spine bone mineral density (BMD) at 2 years based on intention-to-treat analysis was 4.64 (1.01) in group A, 6.10 (0.87) in group B and 1.13 (1.32) in group C. Analysis of variance showed significant increases in group A and B compared with placebo (p < 0.01). There were also significant rises in femoral neck BMD for group A (p = 0.005), trochanter BMD for groups A and B (p < 0.01) and total-body BMD for groups A and B (p < 0.001). There was a significant reduction in serum osteocalcin and urinary deoxypyridinoline for groups A and B (p < 0.01). There was an excess of gastrointestinal side-effects in the treated groups, particularly group A. We conclude that intermittent pamidronate therapy can prevent bone loss at both the lumbar spine and femoral neck in patients with established vertebral osteoporosis, although due to gastrointestinal side-effects the 300 mg dose in particular does not appear suitable for clinical usage.

Administration, Oral↗
PubMed1991

Screening for vertebral osteoporosis using individual risk factors. The Multicentre Vertebral Fracture Study Group.

Osteoporosis is a major cause of ill health in postmenopausal women. Several risk factors for osteoporosis have been identified, and they have been widely recommended as a means of identifying subgroups of postmenopausal women who might benefit from prophylaxis and therapy. Evidence to support this use of risk factors is currently lacking, however. We have constructed and evaluated a profile of putative risk factors as a means of identifying women attending general practitioners who have sustained vertebral fractures. The overall prevalence of vertebral fractures in the 1012 women (mean age 64.4 years) studied was 7.8%. Women who had sustained vertebral fractures in this population were significantly (p less than 0.05) older and shorter than those without fractures. They reported a significantly (p less than 0.05) earlier menopause, lower parity and a greater prevalence of hyperthyroidism. However, the best screening instrument devised was not sufficiently predictive to warrant widespread use.

Aged↗
PubMed1988

Evidence for excitatory 5-HT2-receptors on rat brainstem neurones.

1. The technique of microiontophoresis was used to investigate the identity of the receptor mediating the excitatory effects of 5-hydroxytryptamine (5-HT) upon neurones in the midline of the medullary brainstem of the rat in vivo. 2. The 5-HT1-like receptor agonists 5-carboxamidotryptamine (5-CT) and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) failed to excite the majority of neurones excited by 5-HT. The mobilities of 5-CT and 8-OH-DPAT when tested in vitro were found not to differ significantly from that of 5-HT, suggesting that the lack of effect of these agonists was not due to a lower rate of release from the microelectrodes. 3. The excitatory responses to 5-HT were attenuated by the 5-HT 2-receptor antagonists ketanserin and methysergide when applied microiontophoretically or administered intravenously (0.3 and 1 mg kg-1 respectively). Excitatory responses to glutamate and noradrenaline were not reduced. 4. The 5-HT3-receptor antagonist MDL 72222 failed to attenuate selectively the excitatory response to 5-HT when applied either by microiontophoresis or administered intravenously (1 mg kg-1). 5. Microiontophoretic application of the alpha 1-adrenoceptor antagonist prazosin did not attenuate excitatory responses to either 5-HT or noradrenaline. Intravenously administered prazosin (0.8 mg kg-1) also failed to attenuate excitatory responses to 5-HT, but did block excitatory responses to noradrenaline. 6. These results suggest that 5-HT2-receptors, but not 5-HT1-like receptors, 5-HT3-receptors or alpha 1-adrenoceptors, are involved in the excitatory response of midline medullary neurones to 5-HT.

Action Potentials↗
PubMed1981

Calcium-ion-binding activity in human small-intestinal mucosal cytosol. Purification of two proteins and interrelationship of calcium-binding fractions.

Ca2+-binding activity was investigated in human small-intestinal mucosal cytosol. Binding was detected in fractions with molecular weights of 28000 and about 900000, as determined by gel filtration. No binding was found at molecular weight 12000-13000 (the molecular weight of calcium-binding protein in lower mammalian species) until the cytosol had been subjected to a hollow-fibre-filtration step. The appearance of Ca2+-binding at molecular weight 12000-13000 was associated with a decline in the 28000-mol.wt. calcium-binding fraction. The 12000-13000-mol.wt. fraction contained two distinct calcium-binding proteins. One of these proteins had properties similar to those of pig calcium-binding protein. Antiserum to this protein reacted against the 28000-mol.wt calcium-binding fraction in cytosol from human small-intestinal mucosa and from human kidney. An immunoassay method for one of the calcium-binding proteins was established. In normal duodenal mucosa the concentration was 915 micrograms/g and in the ileum it was 443 micrograms/g of mucosa. A subject with hypercalcaemic sarcoidosis had 1200 micrograms/g of mucosa in the jejunum, and a subject with an undetectable concentration of plasma 25-hydroxycholecalciferol had concentrations of calcium-binding protein in the mucosa similar to those found in normal subjects.

Adolescent↗
PubMed1980

Vitamin D metabolism in patients treated with phenytoin and phenobarbitone.

There are many reports of abnormalities in calcium metabolism and even of frank osteomalacia in patients taking anticonvulsant drugs. Although enzyme induction has been suggested to be the cause of increased requirements for vitamin D leading to these changes, this has still to be proved. We have studied the metabolism of [3H]cholecalciferol and 25-hydroxycholecalciferol in subjects taking anticonvulsant drugs. The rate of removal of cholecalciferol from the plasma was no different from that in control subjects and no abnormality was detected in the production of disappearance of 25-hydroxycholecalciferol. However, plasma concentrations of 25-hydroxycholecalciferol fell more rapidly during the winter in epileptic subjects than in control subjects. Our results do not confirm that these changes are due to enzyme induction.

Calcifediol↗
PubMed1979

Relative contributions of diet and sunlight to vitamin D state in the elderly.

In winter the vitamin D state of elderly people may reach levels associated with osteomalacia, although the disease may not be clinically apparent. A statistical correlation was observed in a group of elderly subjects during the winter between dietary vitamin D intake and vitamin D state, but the intake was generally too low to make a biologically important contribution to maintaining vitamin D concentrations. Ultraviolet light (UVL) is the primary determinant of vitamin D state in summer and winter, in winter owing to the pools of vitamin D built up during the previous summer. Plasma concentrations of 25-hydroxy vitamin D (25-OHD) in winter of 15.0-22.5 nmol/l (6-9 ng/ml) require that the concentration in the previous summer was over 40 nmol/l (16 ng/ml). To maintain plasma concentrations in the elderly above those associated with osteomalacia a mean dietary vitamin D intake of over 5 microgram/day is required. A more physiological approach, however, would be to increase exposure to UVL.

Aged↗
PubMed1979

Vitamin D metabolism in acute and chronic cholestasis.

To study the effects of acute and chronic cholestasis on vitamin D metabolism we investigated six cases of acute extrahepatic obstructive jaundice and eight cases of primary biliary cirrhosis (PBC) (three supplemented with vitamin D). Plasma 25-hydroxyvitamin D (25OHD) was low in the patients with PBC unsupplemented with vitamin D but normal in obstructive jaundice. None of the patients with PBC showed radiological or histological evidence of osteomalacia. In PBC, dietary intake of vitamin D was low but response to ultra-violet irradiation of the skin was normal even in those with a considerably raised serum bilirubin. Patients with PBC or obstructive jaundice had low levels of 25 hydroxyvitamin D binding protein which correlated with the serum albumin. The half-life of intravenously injected (3)H vitamin D(3) ((3)HD(3)) and the subsequent production of (3)H 25OHD were normal in all the patients with obstructive jaundice and in most with PBC. The two patients with PBC who produced less (3)H 25OHD than expected were receiving vitamin D supplements. The urinary tritium ((3)H) excretion after the injection of (3)HD(3) correlated with the serum bilirubin. After the injection of (3)H 25OHD(3) the urinary excretion of (3)H was minimal and did not correlate with the serum bilirubin, suggesting that the radioactivity appearing in the urine after the (3)H vitamin D(3) injection was associated with vitamin D metabolites other than 25OHD. Factors contributing to the low plasma 25OHD in primary biliary cirrhosis may be a low dietary intake of vitamin D, inadequate exposure to ultra-violet light, and a tendency to urinary wastage of vitamin D metabolites.

Acute Disease↗