Clinical research in primary dental care.

Many commissioning bodies for research expect that researchers will actively involve the public and patients in their projects. The National Institute for Health Research (NIHR), for example, involves members of the public in reviewing funding applications and making recommendations about research funding. The NIHR's portfolio is currently operating in 97% of NHS Trusts and this now includes research sited in primary dental care. This paper presents some case studies of these and other projects which are designed specifically for patient benefit in dental services in the community. This means there is no necessity to translate the outcomes of such research from a university or hospital base to the general population as the projects are undertaken in dental practices that provide primary dental care to (predominantly) NHS patients. The relevance of the outcomes to dental care is, therefore, likely to be of direct interest and importance to commissioners of healthcare funding in the UK who have a duty to use evidence bases for commissioning decisions.

Views on local data management in cancer clinical trials.

The randomized clinical trial is the ultimate method of establishing the value of any new cancer treatment, but the percentage of patients with cancer in the UK who are included in clinical trials of any sort is in single figures. The reasons for this low figure include both patient and clinician factors. The extra work involved in trials is cited repeatedly by clinicians as the main reason for not entering patients into cancer clinical trials. This paper discusses how the provision of local data management could be one important way to improve recruitment into and to ensure the smooth running of clinical trials.

Action of 1,25-dihydroxyvitamin D3 on phospholipid metabolism of human bone cells in culture.

It has recently been proposed that the action of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on bone metabolism may be mediated by changes in phospholipid metabolism. The effects of vitamin D metabolites on the incorporation of radiolabelled precursors into corresponding phospholipid classes were investigated using cells arising from cultured explants of normal human bone with osteoblast-like characteristics. Treatment with 1,25-(OH)2D3 increased the incorporation of serine, measured as the ratio of [3H]serine in phosphatidylserine (PS) to [14C]ethanolamine in phosphatidylethanolamine (PE), in a time- and dose-dependent manner. The maximum effect on PS/PE of 141.6 +/- 5.9% over control (P = 0.022) was observed at a dose of 0.1 nmol 1,25-(OH)2D3/l, maintained for 24 h. Incubations with 25-hydroxyvitamin D3 (0.1 mumol/l) and 24,25-dihydroxyvitamin D3 (10 nmol/l) had no effect. Supraphysiological doses (0.1 mumol/l) of 1,24,25- and 1,25,26-trihydroxyvitamin D3 showed similar effects to those of 1,25-(OH)2D3, emphasizing the importance of 1 alpha-hydroxylation. Incorporation of [14C]choline into phosphatidylcholine, calculated as a ratio to PE, was not affected by treatment with vitamin D metabolites. However, [3H]inositol uptake into phosphatidylinositol was almost doubled when compared with control uptake within 2 h of treatment with 1,25-(OH)2D3 (0.1 mumol/l). This may be of relevance, considering the importance of phosphoinositide metabolism in influencing the intracellular calcium concentration. These results support a role for 1,25-(OH)2D3 in the modulation of phospholipid metabolism in human bone cells, which in turn may be involved in the action of 1,25-(OH)2D3 in bone mineralization.

Remission of hypoparathyroidism during lactation: evidence for a physiological role for prolactin in the regulation of vitamin D metabolism.

We studied a young woman with surgical hypoparathyroidism who, on her usual maintenance dose of calcitriol, developed hypercalcaemia 9 d postpartum when lactation was established. Serum values of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) values were very high (127 pg/ml). The patient remained without exogenous calcitriol treatment for 40 d, during which time serum 1,25(OH)2D3 levels remained within the normal range and serum calcium fell with a half-time of 27 d. The requirements for calcitriol increased to antepartum levels when lactation had ceased. There was a close negative correlation between requirements for calcitriol and serum PRL values. After weaning, an episode of hypercalcaemia was induced by increasing the dose of calcitriol. On stopping calcitriol the serum 1,25(OH)2D3 fell to low values (4 pg/ml) within 2 d and serum calcium fell with a half-time of 3 d, necessitating the early reintroduction of calcitriol. We conclude that in hypoparathyroidism exogenous vitamin D requirements fall during lactation because of enhanced endogenous production of 1,25(OH)2D3. The lactation-associated increase in circulating 1,25(OH)2D3 concentrations thus results from a parathyroid hormone-independent mechanism, possibly by an effect of PRL on the 1 alpha-hydroxylase.

Vitamin D metabolites in patients with established non-union of fracture.

The serum concentrations of vitamin D metabolites and biochemical markers of bone metabolism were measured in 15 patients with established non-union of fracture and in 15 age- and sex-matched controls. No significant differences between the two groups were observed in the concentrations of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3; or in the biochemical indices of skeletal metabolism. These results suggest that patients with established non-union have normal bone turnover with no evidence of disturbed production or utilization of 24,25-dihydroxyvitamin D3 or other major vitamin D metabolites. Disturbances in vitamin D metabolism are unlikely therefore to make a major contribution to the maintenance of non-union of fracture.