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Biomedical subjects

L F Hill

Publications and source records attributed to L F Hill.

8 recordsLinked to original sources

Vincristine therapy for thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is a rare disorder characterized by microangiopathic haemolytic anemia, consumption thrombocytopenia, renal impairment, neurological dysfunction, and fever, but all these features are not present in every patient. Although the prognosis of TTP has improved since it was demonstrated that large volumes of fresh frozen plasma (FFP) lead to a remission in most patients, the disease remains fatal in many instances. Therefore, other therapies are often used in TTP, but there is skepticism about their value, since such treatments are often used in combination, making evaluation difficult. This report describes three patients with TTP and a consistent therapeutic response occurring 5 days after vincristine in each of four instances.

Adult

1,25-dihydroxycholecalciferol in hypoparathyroidism.

8 patients with hypoparathyroidism have been treated successfully with 1,25-dihydroxycholecalciferol (0-25-1-0 mug/day) for 4-24 mo. Normal serum-calcium levels were restored in all patients, but half the patients required supplementary oral calcium. Treatment reduced serum-phosphorus in all patients, but values remained high in 3, and the renal-tubular reabsorption of phosphate returned to normal in only 2 of the 8 patients. A comparison is made with the effects of oral therapy with massive amounts of calcium salts. The data obtained are discussed in relation to the probable mode of therapeutic action of 1,25-dihydroxycholecalciferol.

Administration, Oral

Cerebrospinal fluid absorption in primary hypoparathyroidism.

Cerebrospinal fluid absorption has been studied in a patient with primary hypoparathyroidism, papilloedema, and epilepsy. A marked reduction of cerebrospinal fluid transport into plasma was demonstrated which returned to normal after correction of the hypocalcaemia.

Adult

Metabolic fate of administered 1,25-dihydroxycholecalciferol in controls and in patients with hypoparathyroidism.

In four healthy controls and three patients with hypoparathyroidism serum-1,25-dihydroxycholecalciferol (1,25-D.H.C.C.) concentrations, after oral or intravenous administration, declined biphasically with a rapid-phase half-time of about 14 hours. Repeated oral doses of 1 mug 1,25-D.H.C.C. (2-4 nmol) produced serum concentrations well below the assayed normal range but were nevertheless effective in raising serum-calcium. It is suggested that orally administered 1,25-D.H.C.C. acts directly on the intestinal mucosal-cell nucleus to promote calcium absorption. 1,25-D.H.C.C. is more rapidly eliminated from the body than vitamin D, and it is predicted that any hypercalcaemia caused by 1,25-D.H.C.C. therapy should be of relatively short duration.

Administration, Oral

Treatment of hypoparathyroidism with 1,25-dihydroxycholecalciferol.

Five patients with hypoparathyroidism (three post thyroidectomy and two idiopathic) were treated with synthetic 1,25-dihydroxycholecalciferol (1,25-(OH)2-D3) for up to 6 months. In each case daily oral administration of 1 microgram 1,25-(OH)2-D3, either alone or with additional calcium, raised ther serum calcium into the normal range. The serum phosphorus and the renal tubular reabsorption of phosphorus fell during treatment. None of these patients developed hypercalcaemia and no other complications of treatment have been recorded. 1,25-(OH)2D3 seems to represent a significant improvement over conventional methods for treating hypoparathyroidism.

Adult

Vitamin D metabolism and parathyroid function in man.

1. The metabolism of an intravenous pulse dose of double-isotope-labelled cholecalciferol has been studied in control subjects with widely differing states of vitamin D nutrition and in patients with primary disorders of parathyroid function. 2. The formation of labelled 1,25-dihydroxy-cholecalciferol [1,25-(OH)2D3] and labelled 24,25-dihydroxycholecalciferol [24,25-(OH)2D3] has been related to the prevailing concentrations in serum of 25-hydroxycholecalciferol [25-(OH)D3], immunoreactive parathyroid hormonel, calcium and orthophosphate (Pi). 3. In control subjects with relative vitamin D deficiency [serum 25-(OH)2D3 was related inversely to the serum 25-(OH)D3 and serum calcium, and directly to serum immunoreactive parathyroid hormone. No formation of 1,25-(OH)2D3 was detectable to form labelled 24,25(OH)2D3 preferentially. 4. No control subject produced significant amounts of both labelled 1,25-(OH)2D3 and labelled 24,25-(OH)2D3 simultaneously. 5. All subjects with primary hyperparathyroidism produced significant amounts of labelled 1,25-(OH)2D3 and labelled 24,25-(OH)2D3 simultaneously; the renal turnover of 25-(OH)D3 was apparently greater than in nutritionally matched controls. Serum labelled 1,25-(OH)2D3 in this disease was not correlated with serum 25-(OH)D3, immunoreactive parathyroid hormone, calcium or Pi. Production of labelled 24,25-(OH)2D3 was inappropriately high for the prevailing nutritional state. 6. The indirectly estimated their concentration of 1,25-(OH)2D3 showed only a fourfold variation in control subjects (45-180 pmol/l), compatible with its having a regulated hormonal function. 7. The data suggest that the production of 1,25-(OH)2D3 from a pulse dose of cholecalciferol is normally regulated, directly or indirectly, by the parathyroid hormone.

Adult

Vitamin d and the kidney.

The biologically active form of vitamin D3, 1,25-dihydroxycholecalciferol is produced by the kidney. The biosynthesis of 1,25-dihydroxycholecalciferol from 25-hydroxycholecalciferol is apparently controlled and important factors in this control are dietary calcium and phosphorus, and parathyroid hormone secretion. The direct effects of vitamin D and its metabolites on renal function are uncertain. Patients with chronic renal failure have defective synthesis of 1,25-dihydroxycholecalciferol. Uremic patients treated with small doses of 1,25-dihydroxycholecalciferol or 1 alpha-hydroxycholecalciferol show increased intestinal calcium absorption and bone healing.

Animals