[Vitamin D--from vitamin to hormone. I 25-hydroxyvitamin D].
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Humans↗
Biomedical subjects
B Lund
Publications and source records attributed to B Lund.
[Chloroquine poisoning. A review and a case of acute poisoning].
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Adult↗
The relationship between plasma concentration and plasma disappearance rate of immunoreactive insulin in normal subjects.
To investigate the mechanism of insulin degradation in normal subjects, a kinetic model of insulin disappearance was constructed: insulin was assumed to be extracted from plasma by two independent processes, one saturable and one non-saturable. On the basis of these assumptions, a linear (non-proportional) relationship between steady-state plasma insulin concentration and steady-state plasma disappearance rate was predicted over the concentration range studied. Constant infusion experiments were performed on eight healthy normal subjects, normoglycaemia and fasting plasma C-peptide concentrations being maintained during the experiments. Agreement was found between the predictions of the model and the experimental results, and it is concluded that insulin degradation in normal subjects may be described in terms of two processes: one that is saturated at physiological plasma insulin concentrations and one that is apparently non-saturable over a wide concentration range.
Antigens↗
Delayed fracture healing following jejunoileal bypass surgery for obesity.
A 38-year-old woman, who 5 years earlier had undergone a jejunoileal bypass for gross obesity, fractured the distal forearm by a minor trauma. Circulating 25-hydroxycholecalciferol was undetectable without vitamin D3 supplement but increased to the lower normal range on a daily dose of 1200 units of vitamin D3. Serum 1,25-dihydroxycholecalciferol was, however, in the upper normal range, both without and with vitamin D supplement. After intestinal reanastomosis the fracture healed and the biochemical changes normalized. Malabsorption due to reduced amount of functioning intestine may cause severe metabolic bone disease, which may not always be reverted by a high-calcium diet and vitamin D supplementation.
Adult↗
Serum levels of vitamin D metabolites and bone remodelling in hyperthyroidism.
Serum levels of 25-hydroxyvitamin DF, 24,25-dihydroxyvitamin D and 1,25-dihydroxyvitamin D were measured in 25 untreated hyperthyroid patients in whom histomorphometric evaluations of iliac crest bone biopsies were performed after in vivo tetracycline doublelabeling. The serum concentration of 25-hydroxyvitamin D was normal. The serum concentration of 1,25-dihydroxyvitamin D was reduced (p less than 0.02) compared to normal whereas the serum concentration of 24,25-dihydroxyvitamin D was increased (p less than 0.02). The bone changes were characterized by an enhanced turn-over in trabecular and cortical bone leading to an increased porosity of cortical bone and mobilisation of bone mineral. The observed changes in vitamin D metabolism could be explained by a reduced renal 1-alpha-hydroxylase activity secondary to hypercalcaemia with suppressed parathyroid secretion and hyperphosphataemia. The bone changes were unrelated to the serum levels of vitamin D metabolites. In trabecular bone the appositional rate and mineralization rates of osteoid were increased and the mineralization lag time was shortened showing that the mineralization and formation of osteoid in the hyperthyroid state can progress with an enhanced rate in spite of a reduced mean serum level of the active vitamin D metabolite, 1,25-dihydroxyvitamin D.
24,25-Dihydroxyvitamin D 3↗
Altered vitamin D metabolism and bone remodelling in patients with medullary thyroid carcinoma and hypercalcitoninemia.
Fourteen patients with medullary carcinoma of the thyroid (MCT) and hypercalcitoninemia were studied. Serum concentrations of calcium, phosphorus and iPTH (C-terminal) were normal. Serum 1,25-dihydroxyvitamin D (1,25-(OH)2D) levels were increased (p less than 0.001) in spite of reduced serum 25-hydroxyvitamin D (25-OHD) levels (p less than 0.02) indicating an enhanced activity of the renal 1 alpha-hydroxylase. Serum 24,25-dihydroxyvitamin D levels were normal and correlated positively with serum 25-OHD. Histomorphometric analyses of iliac crest bone biopsies after in vivo tetracycline double-labelling were performed in patients and controls. The patients showed a normal trabecular bone volume. The mean size of the cortical osteocytic lacunae was increased (p less than 0.001). Significant increases were found in fractional formation surfaces (p less than 0.05), fractional labelled surfaces (p less than 0.01) and fractional resorption surfaces (p less than 0.005) in trabecular bone. The appositional rate of newly mineralized bone was reduced (p less than 0.025). The mean osteoid seam width was normal due to an unchanged mineralization lag time and a normal osteoid appositional rate. The bone formation rate at tissue level was high normal. The altered vitamin D metabolism may be caused by a direct effect of hypercalcitoninemia on the renal l alpha-hydroxylase or may represent an adaptive change in calcium-phosphorus homeostasis. The dynamic bone changes are similar to those found in primary hyperparathyroidism and may be caused by an enhanced sensitivity to circulating PTH induced by the increased 1,25-(OH)2D.
Adolescent↗
cis-Dichlorodiammineplatinum (II) and hexamethylmelamine in advanced ovarian carcinoma: a phase II study.
Thirty-eight previously treated patients with ovarian carcinoma received a combination of cis-dichlorodiammineplatinum (II) (CDDP) and hexamethylmelamine (HMM). The schedule was CDDP 75 mg/m2 i.v. with forced diuresis on day 1, followed by HMM 200 mg/m2 p.o. on days 8-21, repeated every 4 weeks. In 29 evaluable patients an overall response rate (CR + PR) of 35% with a median response duration of 4.5 months was observed. The performance status seemed to be an important prognostic factor. The gastrointestinal- and neurotoxicities were severe and resulted in dose modification and/or drug discontinuation in half of the patients. In conclusion, CDDP and HMM is an active drug combination in advanced ovarian carcinoma resistant to conventional chemotherapy. A possible superiority of this combination compared with CDDP or HMM alone has to await randomized trials.
Adult↗
Protein synthesis in vitro by epaxial muscle polyribosomes from cod, gadus morhua.
1. Ribosomes were isolated from epaxial muscle of cod (Godus morhua). 2. Incorporation of amino acids into protein was determined in systems containing liver cell sap from rat or rainbow trout (Salmo gairdneri R.). Maximal rates were at 35 degrees and 28 degrees C, respectively. The optimum pH was between 7.5 and 8.0. 3. Ribosomes isolated from muscle stored at -80 degrees C between 1 and 14 days retained 86% of the activity of ribosomes from fresh tissue. 4. Starvation of fish for 10 days reduced amino acid incorporating activity of isolated ribosomes to 15-20%. 5. All ribosome preparations used in the experiments were analysed by sucrose density gradient centrifugations.
Animals↗
Serum 1,25-dihydroxyvitamin D in normal subjects and in patients with postmenopausal osteopenia. Influence of age, renal function and oestrogen therapy.
The serum concentrations of 1,25-dihydroxyvitamin D (1,25-(OH)2D) were measured in 194 healthy subjects aged 15-90 years. The mean level was 32.8 +/- 12.5 pg/ml (SD) without age-dependent changes. The mean serum concentration was reduced (26.9 +/- 13.6 pg/ml) in 55 patients with postmenopausal osteopenia compared to 62 non-osteopenic age-matched controls (32.8 +/- 11.6 pg/ml) (p less than 0.02). The serum concentrations correlated positively with the creatinine clearances in 23 osteopenic patients studied. Treatment with oestradiol increased serum 1,25-(OH)2D significantly in postmenopausal women. A reduced production of 1,25-(OH)2D or a reduced sensitivity to this hormone may play a significant role in the pathogenesis of postmenopausal osteopenia.
Adolescent↗
Acute effects of parathyroid hormone on vitamin D metabolism in patients with the bone loss of aging.
This study was carried out to evaluate the effects of an iv injection of parathyroid extract on serum levels of 1,25-dihydroxyvitamin D [1,25-(OH)2D3] in elderly osteopenic patients and age-matched nonosteopenic controls. Serum concentrations of 1,25-(OH)2D were reduced in elderly osteopenic subjects (mean +/- SEM, 20 +/- 3 pg/ml) compared with values in age-matched nonosteopenic controls (35 +/- 3 pg/ml), whereas no differences were found in serum 24,25-dihydroxyvitamin D levels (1.5 +/- 0.3 and 2.2 +/- 0.5 ng/ml, respectively). An iv injection of parathyroid extract was followed by a significant increase in serum 1,25-(OH)2D levels in both osteopenic patients (16 +/- 6 pg/ml) and controls (15 +/- 5 pg/ml). The mean 4-h increases in serum 1,25-(OH)2D of 11-18 pg/ml were not significantly different in the two groups. The results indicate that the reduced 1,25-(OH)2D concentrations in the osteopenic patients are secondary to changes in factors that normally stimulate this enzyme system.
24,25-Dihydroxyvitamin D 3↗
Vitamin D metabolism and osteomalacia in patients with fractures of the proximal femur.
A high frequency of histological osteomalacia (25 per cent) was seen in patients with fractures of the proximal femur. No correlation was found between the levels of circulating 25-hydroxyvitamin D (25-OHD) or 1,25-dihydroxyvitamin D (1,25-(OH)2D) and the bone histomorphometric changes. The serum 25-OHD levels were normal, which excludes a dietary vitamin D deficiency or a reduced hepatic hydroxylation of the vitamin. The mean serum 1,25-(OD)2D concentration was significantly reduced in the whole patient group, but surprisingly the levels were normal in those with histological osteomalacia, indicating that an impaired conversion of 25-OHD to 1,25-(OH)-2D was not the primary cause of the bone disease. A reduced sensitivity to 1,25-(OH)2D might be a possible explanation for the osteomalacia.
Anthropometry↗
Influence of diphenylhydantoin on isotope release and bone enzymes in vitro.
The acute effect of diphenylhydantoin isotope release in an in vitro system using mouse calvaries was studied. A depressive effect on bone resorption was found involving radioactive calcium as well as tritiated proline. Bone resorption and formation were further investigated by semiquantitative histochemistry. Depressed activity of both alkaline and acid phosphatase was found, indicating a direct inhibitory effect of diphenylhydantoin on bone turnover.
Acid Phosphatase↗
Leucine incorporation into skeletal muscle proteins in vitro and protein synthesis by isolated ribosomes from skeletal muscle around a high velocity missile injury.
Protein synthesis in skeletal muscle around a high velocity missile injury was investigated in two series of experiments. In the first series a shot wound was induced in the hindleg of dogs. Muscle biopsies were taken at various distances from the wound channel and bundles of muscle fibre were incubated in a medium containing 14C-leucine under protein synthetizing conditions. A significant reduction in the rate of leucine incorporation into muscle protein was seen in the adjacent to the wound channel. At a distance of 3 cm from the bullet track no reduction in leucine incorporation into protein occurred. In the second series of experiments a high velocity missile injury was induced in the hindleg of pigs. The capacity of ribosomes to incorporate 14C-phenylalanine into protein was analyzed. Ribosomes were isolated from skeletal muscle around the shot wound. The effect of missile injury alone and that of the combined effect of missile injury and hemorrhage were studied. A marked reduction in ribosomal activity was found in tissue adjacent to and up to 2.4 cm from the wound channel. At a distance of 3 cm from the wound ribosomal activity remained unaffected. Ribosomal activity was significantly more reduced in tissue close to the wound channel after missile injury and hemorrhage than after missile injury alone. The reduced capacity for protein synthesis in muscle around the missile injury found in this study probably reflects a lowered cellular energy level. The local metabolic changes were aggrevated in animals where hemorrhage was also induced indicating that in the clinical situation prevention of hemorrhage and hypovolemia might reduce the amount of tissue that has to be excised following a short wound.
Animals↗
Vitamin D deficiency in obese patients and changes in circulating vitamin D metabolites following jejunoileal bypass.
The serum levels of the three major vitamin D metabolites [25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyitamin D (1,25-(OH)2D), 24,25-dihydroxyvitamin D (24,25-(OH)2 D)] and immunoreactive parathyroid hormone (iPTH) were measured in 14 morbid obese patients, who later on were subjected to jejunoileal bypass surgery. The preoperative median values of 25-OHD and 24,25-(OH)2D were reduced compared with controls (P less than 0.001), whereas elevated concentrations were found of 1,25-(OH)2D (P less than 0.005). Median levels of iPTH in the obese group were significantly higher than those found in normal subjects (P less than 0.001). A decrease was observed in serum concentrations of all three vitamin D metabolites following jejunoileal bypass (P less than 0.005). An increase in the serum levels of iPTH and alkaline phosphatase was seen postoperatively (P less than 0.002), probably indicating a secondary hyperparathyroidism. The results show that the vitamin D metabolism is slightly abnormal in severely obese patients. Jejunoileal bypass is followed by severe disturbances of vitamin D metabolism.
24,25-Dihydroxyvitamin D 3↗
[Steadily increasing uncertainty regarding work for young doctors in Norway].
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Employment↗
Reduced 2,25-dihydroxyvitamin D and 24,25-dihydroxyvitamin D in epileptic patients receiving chronic combined anticonvulsant therapy.
Thirty-one adult epileptic outpatients on chronic combined anticonvulsant therapy were investigated. Eleven patients took vitamin D2 supplementation 400-1200 IU/day as multivitamin tablets. Mean serum calcium and renal calcium excretion were reduced. Serum alkaline phosphatase and urinary hydroxyproline excretion were increased. Forearm bone mineral content was reduced. Serum concentrations of 25-hydroxyvitamin D (25-OHD), 24-25-dihydroxyvitamin D (24,25-(OH)2D) and 1,25-dihydroxyvitamin D (1,25-(OH)2D) were reduced (p less than 0.001). A positive correlation was found between the serum 25-OHD and 24,25-(OH)2D concentrations (p less than 0.05) with the highest levels in those receiving vitamin D2 supplementation (p less than 0.01). Serum 1,25-(OH)2D correlated positively with renal calcium excretion (r = 0.65, p less than 0.001) suggesting that the intestinal calcium absorption in epileptic patients depends on 1,25-(OH)2D levels.
24,25-Dihydroxyvitamin D 3↗
Calcium and vitamin D metabolism in acromegaly.
Acromegalic subjects were found to have elevated serum levels of both 1,25-dihydroxyvitamin D (1,25-(OH)2D), 67 +/- 22 (SD) pg/ml) and 24.25-dihydroxyvitamin D (24.25-(OH)2D), (6.9 +/- 1.5 (SD) ng/ml). The serum concentration of 1,25-(OH)2D correlated positively (P less than 0.02, R = 0.56) to the 24 h urinary excretion of growth hormone, but not to the serum levels of parathyroid hormone, prolactin, thyroid hormones or the urinary excretion of free cortisol. Fourteen patients were treated with bromocriptine at doses from 15-45 mg/day for a period of about 6 months. This was accompanied by a significant decrease in the urinary excretion of growth hormone and calcium and in the serum concentrations of 1,25-(OH)2D and 24.25-(OH)2D. A relationship was demonstrated between the decrease in urinary calcium excretion and the decrease in serum 1,25-(OH)2D (P less than 0.02, R = 0.64). It is concluded that the serum concentration of 1,25-(OH)2D is elevated in acromegaly, perhaps as a consequence of a direct action of growth hormone on the renal 1 alpha-hydroxylase activity.
Acromegaly↗
Trochanteric and subtrochanteric fractures. The operative results in a prospective and comparative study of Ender nailing and McLaughlin Osteosynthesis.
A comparative and prospective study was performed in order to evaluate the advantages or disadvantages of the Ender operation in comparison with the McLaughlin technique. The series included 145 patients, 72 operated by the Ender method, and 73 by the McLaughlin method. There were no differences between the two groups as regards anaesthesia time, operation time, mean stay in hospital, morbidity and mortality. Technical problems were encountered in 40 of the Ender operated fractures (56 per cent), whereas the figure for the patients treated with the McLaughlin method was 17 (23 per cent). Ten (14 per cent) patients in the Ender group but only 2 (3 per cent) in the McLaughlin group needed re-operation. Three deep infections occurred in the McLaughlin group, but non in the Ender group. It was concluded that the only advantage which could be demonstrated in the Ender group was a low infection rate. Many disadvantages were revealed, the most outstanding being the many technical problems encountered and the great number of re-operations required.
Adult↗