HLA in multiple endocrine adenomatosis (type I).
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Biomedical subjects
Publications and source records attributed to M Davie.
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To study the effects of acute and chronic cholestasis on vitamin D metabolism we investigated six cases of acute extrahepatic obstructive jaundice and eight cases of primary biliary cirrhosis (PBC) (three supplemented with vitamin D). Plasma 25-hydroxyvitamin D (25OHD) was low in the patients with PBC unsupplemented with vitamin D but normal in obstructive jaundice. None of the patients with PBC showed radiological or histological evidence of osteomalacia. In PBC, dietary intake of vitamin D was low but response to ultra-violet irradiation of the skin was normal even in those with a considerably raised serum bilirubin. Patients with PBC or obstructive jaundice had low levels of 25 hydroxyvitamin D binding protein which correlated with the serum albumin. The half-life of intravenously injected (3)H vitamin D(3) ((3)HD(3)) and the subsequent production of (3)H 25OHD were normal in all the patients with obstructive jaundice and in most with PBC. The two patients with PBC who produced less (3)H 25OHD than expected were receiving vitamin D supplements. The urinary tritium ((3)H) excretion after the injection of (3)HD(3) correlated with the serum bilirubin. After the injection of (3)H 25OHD(3) the urinary excretion of (3)H was minimal and did not correlate with the serum bilirubin, suggesting that the radioactivity appearing in the urine after the (3)H vitamin D(3) injection was associated with vitamin D metabolites other than 25OHD. Factors contributing to the low plasma 25OHD in primary biliary cirrhosis may be a low dietary intake of vitamin D, inadequate exposure to ultra-violet light, and a tendency to urinary wastage of vitamin D metabolites.
A dietary survey has been carried out of elderly people with osteomalacia. The commonest type of osteomalacia was that associated with partial gastrectomy. Although a dietary deficiency of vitamin D has been suggested as a cause of the osteomalacia the intake of this substance was not significantly different from that in controls to explain the development of the disease. It was found, however, that patients with osteomalacia went outside much less than controls and given the contribution of sunlight to meeting vitamin D requirements it is suggested that further consideration should be given to this factor in the aetiology of post-gastrectomy osteomalacia.
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Vitamin D metabolism was investigated in 10 patients with cirrhosis. Mean plasma 25 hydroxycholecalciferol (25 OHD) centration in alcoholic cirrhosis was lower than in controls but the difference was not significant. In three patients restudied after the summer, plasma 25 OHD had risen. In contrast to the finding in normal subjects, the half-life of intravenously administered 3H cholecalciferol was short in cirrhotics and showed no correlation with plasma 25 OHD. Furthermore, the appearance of 3H 25 OHD from 3H cholecalciferol was reduced compared to the control group four hours after injection. Increased rate of metabolism of cholecalciferol and deficient production of 25 ohd contribute to vitamin D deficiency in liver disease.
Hyperparathyroidism is the commonest presenting feature in multiple endocrine adenomatosis Type I (MEA Type I), the other manifestations may be delayed for many years or appear only in relatives. A family now diagnosed as MEA Type I, who was previously thought, in 1965, to have familial hyperparathyroidism due to chief cell hyperplasia is now described. The importance is stressed of family surveillance and long-term follow-up in all cases of primary hyperparathyroidism. Those tests that are essential in the long-term surveillance of the patients and their first degree relatives are discussed.
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Human granulocytes (PMNL) were successfully cryopreserved for up to 14 months. The PMNL (1-2 X 10(7)/ml) were stored in 2-ml ampoules in the gas phase of liquid nitrogen at a temperature between -160 degrees C and -196 degrees C using dimethylsulphoxide (DMSO 10%) as cryoprotectant. Morphology and phagocytic and bactericidal capacity were best preserved by adding fetal calf serum to the freezing mixture, by using an interrupted cooling process, by washing the thawed PMNL in fresh freeze-dried plasma, and centrifuging at 600 g for no more than two minutes. Careful post-thaw handling of the cells was an important factor in preserving function. These preliminary studies indicate that useful numbers of PMNL can be recovered in a functional state after storage for long periods in liquid nitrogen.
Thirty episodes of infection in severely neutropenic children with acute leukaemia and aplastic anaemia resistant to antibiotics were treated with total of 51 granulocyte transfusions collected from normal donors by means of an Aminco continuous flow cell separator. The mean granulocyte increment in the recipients was 820/mm3 at 1 hour and 307/mm3 at 15 hours post-transfusion and it showed a correlation with the number of cells transfused, the size of the child, and his pretransfusion granulocyte count. Fifteen (50%) episodes responded clinically by 24 hours and 23 (77%) by 5 days post-transfusion. Two more children recovered more slowly and 5 died. Poor response was associated with multiple-site infections and with a prolonged period of infection before granulocyte transfusion, but the primary diagnosis did not influence the outcome. We conclude that granulocyte transfusion significantly reduces the mortality and morbidity from infection in neutropenic children with acute leukaemia.