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Biomedical subjects

S W Kooh

Publications and source records attributed to S W Kooh.

At least 55 records · Page 3Linked to original sources
PubMed1980

Parathyroid hormone responsiveness in the sheep fetus and newborn lamb.

Responsiveness of the sheep fetus to parathyroid hormone (PTH) infusion was studied in the unanesthetized fetus in situ and the results were compared with those obtained in the newborn lamb, PTH, 0.5 USP U/min per kilogram body weight was infused intravenously to four sheep fetuses in utero (gestational age 127-141 days) and 10 newborn lambs (1-20 days of age). PTH infusion increased plasma Ca in the fetus and the PTH-induced hypercalcemia increased plasma calcitonin although the maternal levels of Ca and calcitonin did not change. In the fetus, as well as in the newborn lamb, PTH decreased the percentage tubular reabsorption of phosphate (TRP) and increased urinary excretion of cAMP. These results indicate that the sheep fetus has developed the target organ responsiveness to PTH and a normal calcitonin secretory mechanism by the last trimester of gestation.

Animals↗
PubMed1980

25-hydroxyvitamin D3 metabolism by isolated perfused rat kidney.

Kidneys of adult rats were removed and perfused with semisynthetic media with the object of elucidating the separate actions of factors implicated as modulators of renal metabolism of 25-hydroxyvitamin D3 (25(OH)D3). During a 3-h perfusion with 3[H]25(OH)D3, the kidney produced high yields of 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) or 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) depending on whether the rat had previously been, respectively, normocalcemic, normophosphatemic, vitamin D-replete or hypocalcemic, hypophosphatemic, vitamin D-deplete. With longer perfusion (up to 12 h), kidneys from normocalcemic, normophosphatemic, vitamin D-replete rats mainly produced 24,25(OH)2D3 but also amounts of 1,25(OH)2D3. This pattern was unaltered by reducing Ca or Pi concentrations of perfusate or by adding parathyroid hormone. Kidneys of hypocalcemic, hypophosphatemic, vitamin D-deplete rats perfused with low Ca, low Pi medium for 12 h at first produced 1,25(OH)2D3 exclusively. However, 24,25(OH)2D3 appeared after 4 h and accumulated thereafter, whereas 1,25(OH)2D3 synthesis ceased after 7 h, a metabolic pattern unaffected by the concentration of substrate or end products in the perfusate or by addition of cyclic AMP. The model shows promise for studying regulation of 25(OH)D3 metabolism by the kidney.

Animals↗
PubMed1980

25-hydroxyvitamin D metabolism in the sheep fetus and lamb.

The metabolism of [3H]-25-hydroxyvitamin D3(3H-25-OH-D3) to [3H]-1,25-dihydroxyvitamin D3 (3H-1,25-(OH)2D)3 and [3H]24, 325 dihydroxyvitamin D3 (3H-24,25-(OH)2D3) was studied in sheep fetuses and lambs. In vivo metabolism was observed by chromatography of extracts of plasma obtained 24 hr after direct iv injection of 3H-25-OH-D3 to the fetus and lamb. The renal enzymes 25-hydroxyvitamin D-1-hydroxylase and -24-hydroxylase were determined in vitro by quantitative assay. In fetal lambs, 3H-24,25-(OH)2D3 was consistently the only detectable dihydroxyvitamin D3 metabolite; this was confirmed by the in vitro studies in which 24-hydroxylase was the only detectable enzyme. Parathyroid hormone infusion to the fetus did not stimulate 3H-1,25-(OH)2D3 production. In normal lambs fed sheep's milk or cow's milk 3H-24,25-(OH)2D3 was the only metabolite of 3H-25-OH-D3 in vivo and only 24-hydroxylase activity was detected in vitro. In lambs fed a low-calcium, vitamin D-free formula, 24-hydroxylase activity remained measurable for at least 11 days of feeding, and by that time 1-OHase activity became evident in vitro. Appreciable 3H-1,25-(OH)2D3 was not observed in plasma until 16 days of feeding with the formula. After 18 days on low-calcium, vitamin D-free formula, 1-OHase was the only detectable 25-OH-D3 metabolizing enzyme. We also studied the rates at which 3H-25-OH-D3, 3H-24,25-(OH)2D3 and 3H-1,25-(OH)2D3 disappeared from the lamb plasma compartment. Within 1 hr, 3H-1,25-(OH)2D3 fell to 50% of its initial concentration, and after 72 hr only 2% was left. In the case of 3H-25-OH-D and 3H-24,25-(OH)2D3, 50% of each metabolite was left after 7 to 10 hr and about 20% after 72 hr. The rapid disappearance of 3H-1,25-(OH)2D3 may explain the low levels or absence of this metabolite observed in the plasma of some animals shown to have renal 1-hydroxylase activity.

Animals↗
PubMed1979

Pathogenesis of rickets in chronic hepatobiliary disease in children.

To investigate whether hepatobiliary rickets is caused by defective intestinal absorption of vitamin D or by impaired hepatic hydroxylation of the vitamin, we studied three children who developed severe rickets, hypocalcemia, and hypophosphatemia, two despite having received 400 to 800 IU vitamin D per day by mouth, and one despite prolonged treatment with 10,000 IU daily. On oral vitamin D therapy, plasma vitamin D and 25-hydroxyvitamin D levels were low. When two children were treated with weekly intravenous doses of 3,000 IU vitamin D to approximate the recommended prophylactic allowance, their plasma calcium and phosphate values improved promptly, the radiographic lesions healed, and the plasma concentrations of vitamin D and 25-hydroxyvitamin D became normal. Our studies indicate that the primary cause of hepatobiliary rickets is intestinal malabsorption of vitamin D, not impairment of the hepatic metabolism of the vitamin.

Biliary Tract Diseases↗
PubMed1977

Keratitis with hypoparathyroidism.

Chronic kiratitis developed in two children with nonsurgical hypoparathyroidism, as part of an autosomal recessive syndrome that included adrenal insufficiency and moniliasis in what was postulated to be an autoimmune disease. The corneal changes may also have been caused by autoimmune mechanism. Activity of the keratitis diminished once the hypoparathyroidism had been brought under control. However, these patients were thought to be at risk for adrenal insufficiency: neither had moniliasis or adrenocortical insufficiency at present, but the features of the hypoparathyroidism adrenal insufficiency-moniliasis syndrome appeared at different ages and in differing sequences.

Adolescent↗
PubMed1977

Vitamin D therapy in hypoparathyroidism and pseudohypoparathyroidism: weight-related dosages for initiation of therapy and maintenance therapy.

The aims of this study were to determine the dose of vitamin D2 that maintains the serum calcium level within the normal range in hypoparathyroid and pseudohypoparathyroid children and to establish a safe and quickly acting dose for initiating therapy in symptomatic patients. The dose requirement for maintenance therapy was studied in 11 patients and initiation therapy was studied in five newly diagnosed hypocalcemic patients. The results show that (1) the maintenance requirement of vitamin D2 is proportional to body weight and averages 2,000 IU (50 microgram)/kg/day for children of all ages and with all types of hypoparathyroid disorders and the (2) in newly diagnosed symptomatic patients, carefully controlled administration of 8,000 IU (200 microgram) vitamin D2/kg/day for the first one to two weeks corrects hypocalcemia quickly and safely.

Adolescent↗
PubMed1976

Response of protracted neonatal hypocalcaemia to 1alpha,25-dihydroxyvitamin D3.

Six infants with protracted hypocalcaemia (5 classed as tetany of the newborn) had a mean plasma-calcium of less than 6-4 mg/dl and raised plasma-inorganic-phosphate. Four had been hypocalcaemic for longer than 2 weeks despite treatment with low phosphate formulae and extra calcium. All the infants were treated with 1alpha,25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3), usually in a dose of 0-05 mug/kg body-weight/day, administered intravenously for 5--12 days. The plasma-calcium levels began to rise within 24 h after starting 1alpha,25-(OH)2D3 treatment, increased above 7-5 mg/dl within 3 days, and reached the normal range within 8 days. Four of the infants remained normocalcaemic when 1alpha,25-(OH)2D3 was discontinued, but two infants became hypocalcaemic again and required long-term treatment. 1alpha,25-(OH)2D3 has been found safe and dependable as treatment for protracted neonatal hypocalcaemia.

Birth Weight↗
PubMed1976

Increased bone mineral content in young adults with familial hypophosphatemic vitamin D refractory rickets.

Seven adults with familial hypophosphatemia have been investigated by histologic and radiographic examination of bone, and estimates of bone mineral status by in vivo neutron activation analysis (IVNAA). Histological examination showed severe osteomalacia and osteosclerosis in all cases. Radiography showed skeletal deformities and other sequelae of severe rickets of childhood in five of the seven cases, with, in addition, thickened well-mineralized bones; the other two showed normal radiographs. IVNAA measurements showed that the first five had greater than normal bone calcium and that the other two had normal values. Thus, in all cases there is a greater than normal total bone tissue (osteoid and mineralized bone together). The quantitative body calcium measurements show clearly that osteosclerosis occurs in familial hypophosphatemia, confirming the opinions based on histological and radiological data. Although there has been occasional reference to this sclerosis in the literature, up to the present it has received little attention.

Adolescent↗
PubMed1975

Treatment of hypoparathyroidism and pseudohypoparathyroidism with metabolites of vitamin D: evidence for impaired conversion of 25-hydroxyvitamin D to 1 alpha,25-dihydroxyvitamin D.

In hypoparathyroidism and pseudohypoparathyroidism, pharmacologic doses of vitamin D correct hypocalcemia, but the mechanism is unknown. In two children with hypoparathyroidism and one with pseudohypoparathyroidism we tested the hypothesis that in these conditions there is a defect in synthesis of 1 alpha,25-dihydroxyvitamin D3, the principal active metabolite of vitamin D. In both conditions, minute doses of the metabolite (0.04 to 0.08 mug per kilogram of body weight per day) quickly corrected hypocalcemia and increased intestinal calcium absorption. On the other hand, the effective dose of 25-hydroxyvitamin D3 to maintain normocalcemia was 3 to 4 mug per kilogram per day in the two conditions. Thus, the dosage ratio of 25-hydroxyvitamin D3 to 1 alpha,25-dihydroxyvitamin D3 approximated 100:1. By contrast this ratio was approximately 3:1 in two infants with vitamin D deficiency, a condition in which optimal metabolism of vitamin D would be expected. These findings suggest an impaired conversion of 25-hydroxyvitamin D to 1 alpha,25-dihydroxyvitamin D in both hypoparathyroidism and pseudohypoparathyroidism.

Administration, Oral↗