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Biomedical subjects

D J Rowe

Publications and source records attributed to D J Rowe.

86 records · Page 5Linked to original sources
PubMed1972

Plasma levels and therapeutic effect of 25-hydroxycholecalciferol in epileptic patients taking anticonvulsant drugs.

Plasma levels of 25-hydroxycholecalciferol (25-HCC) were measured by a specific competitive protein-binding assay. Mean levels in both normal London adults and adolescent schoolchildren were 16 ng/ml and the mean level in a group of epileptic patients on high-dosage anticonvulsant therapy was 5 ng/ml, (difference from normals P < 0.001). Two further epileptic patients, with well-marked anticonvulsant osteomalacia, were treated with small doses of 25-HCC during full metabolic balance studies; rapid healing followed administration of 25-HCC by mouth in doses of 10-45 mug daily, which is well below the effective dose range of calciferol in this condition. These findings provided further evidence that anticonvulsant osteomalacia results from hepatic enzyme induction which, by increasing the metabolism of cholecalciferol to inactive compounds, lowers 25-HCC levels in patients whose dietary vitamin D intake and exposure to sunlight are otherwise adequate. Results also indicated that under certain circumstances 25-HCC may have considerably stronger antirachitic potency in man than has hitherto been recognized.

Adolescent↗
PubMed1970

Osteomalacia with long-term anticonvulsant therapy in epilepsy.

The investigation and treatment of osteomalacia are described in four patients with epilepsy treated with long-term anticonvulsant therapy. It is suggested that drug-mediated enzyme induction may be the mechanism responsible by causing a greatly increased inactivation of vitamin D in these patients.

Adolescent↗
PubMed1970

Disturbance of calcium metabolism by anticonvulsant drugs.

A survey of calcium metabolism in epileptic patients in a residential centre showed a subnormal serum calcium level in 22.5% of patients and a raised alkaline phosphatase in 29%. Hypocalcaemia was related to high dosage of anticonvulsant drugs, to multiple drug therapy, and to the use of individual anticonvulsant drugs in the following order, with decreasing order of importance: pheneturide, primidone, phenytoin, phenobarbitone. Subnormal serum calcium levels occurred more commonly in patients with a raised liver alkaline phosphatase isoenzyme than in those whose phosphatase was mainly of bone origin.Preliminary results of treatment with calciferol suggested that the disturbance of calcium metabolism was the result of vitamin D deficiency. It is possible that anticonvulsant drugs accelerate the breakdown of vitamin D by liver enzyme induction.

Adolescent↗
PubMed1970

Electrophoretic separation of tissue-specific serum alkaline phosphatases.

Previous electrophoretic methods for the separation of tissue-specific serum alkaline phosphatases have either been unable to separate the liver and bone enzymes or have been too involved for routine clinical use. A relatively simple electrophoretic method is described which separates placental, liver, bone, and intestinal alkaline phosphatases in serum. The clinical applications of such a method appear to be mainly in the differential diagnosis of liver and bone disease, especially in complicated hypercalcaemic states where tumour metastases can affect both bone and liver, in children, and possibly in cirrhosis of the liver.No differences in electrophoretic mobility could be seen between zymograms of different diseases affecting the same organ. Patients presenting with hepatic cirrhosis all showed a marked serum intestinal alkaline phosphatase zone as well as a liver zone on electrophoresis. An intestinal zone was not present with other types of hepatobiliary disease.The heterogeneity of total serum alkaline phosphatase activity in normal subjects is demonstrated, alkaline phosphatases of liver and bone, and sometimes of intestine being present in normal serum. Results obtained in women in the last trimester of pregnancy and in old people are also discussed.

Adolescent↗
PubMedDate not supplied

Relationship between bisphosphonate concentration and osteoclast activity and viability.

Difluoromethylidene bisphosphonate (F2MBP) is one of the many bisphosphonates known to inhibit bone resorption in vitro and in vivo. We have developed an analytical method, employing anion exchange and postcolumn indirect fluorescence detection, by which F2MBP can be quantified in bone samples. The objective of this study was to relate the concentration of F2MBP in embryonic bones treated in organ culture to the physiological effects of the compound, such as bone resorption (i.e., the amount of 45Ca released into the medium from prelabeled bones) and viability of the osteoclast population (i.e., the incidence of abnormal osteoclasts). Osteoclasts in bones treated with F2MBP exhibited morphological features of apoptosis, such as nuclear fragmentation. Both the number and percentage of these abnormal cells increased with dose of F2MBP and duration of incubation. The decrease in normal osteoclasts was correlated with the decreased amount of 45Ca released into the medium. Bones treated with F2MBP for only the first 5 min of the 48-h incubation period had similar numbers of abnormal osteoclasts and amounts of 45Ca released, as had bones incubated with F2MBP continuously for 48 h. The uptake of F2MBP into the bone was rapid. Bones treated with F2MBP for 6 h were similar to bones treated with F2MBP for the entire 48-h incubation period, both in F2MBP concentration and the 45Ca release ratios. These relationships between concentrations of F2MBP within bone and osteoclast activity and viability implicate apoptosis in the mechanism by which this bisphosphonate inhibits bone resorption.

Animals↗
PubMedDate not supplied

Inhibition of bone resorption by difluoromethylene diphosphonate in organ culture.

A newly synthesized diphosphonate, difluoromethylene diphosphonate (F2MDP), was studied for its effects on bone resorption, as measured by the release of previously incorporated 45Ca. F2MDP (10 microM to 1000 microM) effectively inhibited both unstimulated and parathyroid hormone-stimulated resorption, and the amount of 45Ca release decreased with time. Dichloromethylene diphosphonate (Cl2MDP) and ethane-1-hydroxyl-1, 1-diphosphonate (EHDP) inhibited resorption to similar extents with two exceptions: At concentrations of 10 microM and 100 microM, F2MDP was more effective than EHDP and less effective than Cl2MDP. No greater inhibition was observed when bones had been stimulated with PTH prior to the addition of F2MDP. In addition, bones treated with F2MDP only during the first half of the incubation period exhibited reductions in the amount of 45Ca released during the second half similar to that observed when F2MDP was continuously in the medium, indicating a prolonged effect. Morphologic alterations of osteoclasts suggestive of cell degeneration were observed in F2MDP-treated bones, which were similar to those observed in bones treated with Cl2MDP and EHDP. Due to the presence of fluorine, F2MDP may be useful as an experimental tool to investigate the mode of action of all diphosphonates, in addition to its possible use as a therapeutic agent for diseases of increased bone resorption.

Animals↗