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J E Ledger

Publications and source records attributed to J E Ledger.

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Biliary excretion of radioactivity after intravenous administration of [3H]25-hydroxyvitamin D3 in man.

The biliary excretion of radioactivity after intravenous [3H]25-hydroxyvitamin D3 was studied in nine patients with T-tube bile drainage. The mean +/- SD 24-hr radioactivity excretion in T-tube bile expressed as a percentage of the administered dose was 6.7 +/- 2.9%; after correction for incomplete bile collection, the value obtained was 16.0 +/- 11.1%. Chloroform solubility of biliary radioactivity increased from 27.4 +/- 8.9% to 72.9 +/- 10.1% following incubation with beta-glucuronidase. High-performance liquid chromatographic analysis of chloroform extracts of bile revealed that most of the eluted radioactivity was more polar than [3H]25-hydroxyvitamin D3. No free [3H]25-hydroxyvitamin D3 was demonstrated. Thus in man, most of the biliary radioactivity excreted following [3H]25-hydroxyvitamin D3 is in the form of water-soluble compounds, mainly glucuronides. However, our results suggest that glucuronides of metabolites other than 25-OHD3 are predominantly formed.

Adult

Biliary excretion of radioactivity after intravenous administration of 3H-1,25-dihydroxyvitamin D3 in man.

Biliary radioactivity excretion was studied in 10 patients with postcholecystectomy T-tube drainage after intravenous administration of 3H-1,25-dihydroxyvitamin D3. The mean +/- SD radioactivity excreted in T-tube bile expressed as a percentage of the administered dose was 18.9 +/- 10.7% per 24 hours. After correction for incomplete bile collection the value obtained was 28.8 +/- 12.8%. The mean chloroform solubility of the biliary radioactivity increased from 17.0 +/- 8.4% to 69.4 +/- 15.1% after incubation with beta-glucuronidase. High performance liquid chromatography of chloroform extracts of bile revealed that most of the eluted radioactivity was more polar than 1,25(OH)2D3. The percentage radioactivity eluting as 3H-1,25(OH)2D3 increased from approximately 2.4 +/- 1.9 to 16.2 +/- 8.0 after incubation with beta-glucuronidase. We conclude that significant amounts of intravenously administered 3H-1,25(OH)2D3 are excreted in bile, mostly as more polar metabolites. The increase in free 3H-1,25(OH)2D3 after incubation with beta-glucuronidase indicates that glucuronides of 1,25(OH)2D3 are present in bile.

Adult

Vitamin D.

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Enterohepatic Circulation

Faecal tritium excretion after intravenous administration of 3H-25-hydroxyvitamin D3 in control subjects and in patients with malabsorption.

Faecal tritium excretion after intravenous 3H-25-hydroxyvitamin D3 administration was measured in three control subjects and in six patients with small intestine resection or bypass. The mean daily faecal tritium excretion over four to six days ranged from 0.8-1.6% of the injected dose in the controls (mean 1.2) and 0.9-6.8% in the patients (mean 3.7). There was a significant positive correlation between stool volume and the mean daily faecal tritium excretion. No correlation was found between the faecal tritium excretion and the plasma 25-hydroxyvitamin D concentration. Between 2.5 and 19.0% of faecal radioactivity eluted as 3H-25-hydroxyvitamin D3 on silicic acid chromatography. We conclude that faecal loss of endogenous 25-hydroxyvitamin D may be increased after small intestinal resection or bypass. Although the amount lost by this route is relatively small, it may contribute to the development of vitamin D deficiency in patients with malabsorption when endogenous vitamin D3 synthesis is also reduced.

Adult

Vitamin D status and bone histomorphometry in gross obesity.

Plasma 25-hydroxyvitamin D concentrations and bone histomorphometry were investigated in 24 grossly obese subjects. The mean plasma 25OHD concentration was significantly lower in the obese group than in age-matched, healthy controls. Subnormal values were found in four obese subjects and in a further two subjects, who were investigated at the end of the summer, plasma 25-hydroxyvitamin D levels were at the lower end of the normal winter range. Bone histology was abnormal in two patients. In one, mild osteomalacia and secondary hyperparathyroidism were present while in the other patient the appearance suggested increased bone turnover, possibly as a result of healing osteomalacia. We conclude that gross obesity is associated with an increased risk of vitamin D deficiency, probably because of reduced exposure to uv radiation. Histological evidence of metabolic bone disease may also occur. Preoperative vitamin D deficiency may contribute in some patients to the development of metabolic bone disease after intestinal bypass.

Adult