Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A sensitive and simplified radioreceptor assay for 1, 25-dihydroxyvitamin D (1, 25-(OH)2D) in human plasma was described and applied to preliminary clinical studies. Tritium-labeled 1, 25-(OH)2D3 was produced by incubating chick kidney homogenate with tritium labeled 25-hydroxyvitamin D3 (25-OHD3). A cytosol receptor was obtained from rachitic chick intestine (Kd=5.3 X 10(-11) M). Lipids in 5 ml of heparinized human plasma were extracted with dichloromethane, and 1, 25-(OH)2D was isolated by a Sephadex LH-20 column followed by high pressure liquid column chromatography. Recovery of 1, 25-(OH)2D3 after the plasma extraction and chromatography ranged from 58 to 100%. The assay was sensitive to 5 pg/tube. Diluted plasma from a patient on a high dose of 1 alpha-OHD3 showed a dilution curve parallel to the standard curve. The cytosol receptor showed a cross reactivity to various vitamin D3 metabolites physiologically present in the circulation and it was thought to be essential to eliminate other vitamin D3 metabolites 1,25-(OH)2D from plasma samples by high pressure liquid chromatography. Plasma concentrations of 1, 25-(OH)2D were, in the case of most normal subjects, distributed from 7 to 33 pg/ml and the range of distribution became greater in relation to age, indicating that plasma values should be matched to age. Whereas markedly high values of 1, 25-(OH)2D in plasma were found in some cases of primary hyperparathyroidism with prominent bone resorption, relatively low values were seen in some patients with chronic renal failure, senile osteoporosis, osteomalacia and hypercalcemia due to bone metastasis.
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PMID:Competitive protein binding assay for 1,25-dihydroxy-vitamin D in human plasma. 74 68

Here we report a highly sensitive and convenient ligand binding assay for the determination of 1,25(OH)2D3 in small volumes of human plasma. This method involves: (1) extraction of vitamin D3 and its metabolites using methanol-methylene chloride with separation of phases by centrifugation; (2) gel chromatography and high pressure liquid chromatography for the quantitative isolation of 1,25-(OH)2D3; and (3) a sensitive ligand binding assay for 1,25-(OH)2D3 employing cytosol receptor from the intestinal mucosa of rachitic chicks. Using modified rachitogenic chick diets allows early (less than 4 wks) harvesting of active receptor for 1,25-(OH)2D3 in high yield. The method includes a rapid and effective procedure for stable and long-term storage of the active cytosol receptor. A convenient dextran-charcoal means is used for the separation of receptor bound from free 1,25-(OH)2D3 resulting in the achievement of a lower (less than 5%) background (i.e., nonspecific binding) than reported for other 1,25-(OH)2D3 assays. Analysis of this receptor shows it to be a saturable, single class of binding sites with a dissociation constant (Kd) of approximately 3.7 x 10-11. The final recovery of 1,25-(OH)2D3 following extraction and chromatography is 80 +/- 3% and triplicate determinations can be made on a 3 ml plasma sample. The ligand binding assay routinely detects less than or equal to 5pg of 1,25-(OH)2D3 per assay tube and the inter- and intraassay variation, based on repeated determinations of 1,25-(OH)2D3 in pooled normal human plasma, is less than 5%. Preliminary studies indicate that our methodology will permit measurement of plasma 1,25-(OH)2D3 levels in all normal subjects and in pathophysiologic states where 1,25-(OH)2D3 levels may be below or above normal values. 1,25-(OH)2D3 values (pg/ml +/- SEM) in human plasma obtained from both normals and patients with various untreated calcium homeostatic disorders were: normals = 33.5 +/- 1.8; end-stage chronic renal failure = 5.1 +/- 1.2; primary hypoparathyroidism = 18.3 +/- 2.8; primary hyperparathyroidism = 61.4 +/- 7.1; and hyperthyroidism with associated hypercalcemia = 42.1 +/- 8.4.
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PMID:An improved method for the measurement of 1,25-(OH)2D3 in human plasma. 75 33

The rate of reversal of hypercalcaemia or hypercalciuria induced by calciferol, dihydrotachysterol, 1-alpha-hydroxycholecalciferol (1-alpha-OHD3), or 1-alpha, 25-dihydroxycholecalciferol (1-alpha, 25-(OH)2D3) was measured in three normal subjects, two patients with osteoporosis, and 14 patients with disorders resistant to vitamin D. The half time for reversal after stopping 1-alpha, 25 (OH)2D3 was less than that after stopping 1-alpha-OHD3, calciferol, or dihydrotachysterol. The differences observed were independent of the dose given or length of treatment. When 1-alpha-OHD3 or 1-alpha-25-(OH)2D3 was stopped patients with vitamin D resistant states (hypoparathyroidism, renal tubular hypophosphataemia, or chronic renal failure) showed less rapid reversal of hypercalcaemia and hypercalciuria than did normal subjects. These studies show one potential advantage of 1-alpha-25-(OH)2D3 over vitamin D, and possibly over 1-alpha-OHD3, in the management of vitamin D resistant states.
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PMID:Rate of reversal of hypercalcaemia and hypercalciuria induced by vitamin D and its 1alpha-hydroxylated derivatives. 83 19

The effects of small oral doses (1-2 microgram/day) of 1alpha-hydroxycholecalciferol, given for 1 to 2 years, have been examined in four nondialysed adolescents with chronic renal failure and bone disease. Treatment increased calcium retention and plasma calcium, and decreased plasma levels of alkaline phosphatase, hydroxyproline, and immunoreactive parathyroid hormone. X-ray abnormalities of bone regressed, and 2 patients underwent successful surgical correction of knock-knees; bone histology in these 2 was normal at the time of operation. 2 patients developed hypercalcaemia which promptly reversed when 1alpha-hydroxycholecalciferol was withdrawn. In one patient treatment was initially successful, but later there was biochemical, radiographic, and histological evidence of relapse. Long-term treatment of such patients with 1alpha-hydroxycholecalciferol may be effective and facilitate the surgical correction of deformities, but this is not invariable. Toxic effects are similar to those of vitamin D itself, but are more readily reversible.
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PMID:Renal osteodystrophy in nondialysed adolescents. Long-term treatment with 1alpha-hydroxycholecalciferol. 87 33

Five adult patients with chronic renal failure and associated renal osteodystrophy have been treated for 6 months with 1-alpha-hydroxycholecalciferol (1 alpha-OH-D3), a synthetic vitamin D analogue. All 5 patients had severe metabolic bone changes as estimated by bone scintigraphy. Three patients were hypocalcemic, 4 had elevated serum alkaline phosphatases, 5 had elevated serum immunoreactive parathyroid hormone (i-PTH) concentration and 3 had bone pains. During treatment serum calcium increased in all patients (mean 11.4%) and 3 originally hypocalcemic patients became normocalcemic. Serum alkaline phosphatases decreased (mean 27.3%) and became normal in 4 patients, who initially had elevated values. A pronounced decline in the serum concentration of i-PTH (mean 53%) was seen in all patients and 1 patient obtained normal i-PTH levels after 4 months of treatment. The intestinal calcium absorption, which was low initially, even when calcium intake was considered, rose almost threefold (mean 273%) and reached normal values in all cases. The bone mineral content increased in all patients, but the changes were small (mean 4.9%) and insignificant. Finally, bone pain disappeared in 2 patients and improved in 1 of 3 patients exhibiting this symptom. A linear correlation (r = 0.48, p less than 0.001) was found between the dose of 1 alpha-OH-D3 and serum calcium. But in spite of this and the frequent control, all patients developed one episode of hypercalcemia. This disappeared within 48 hours after discontinuing the drug. It is concluded that treatment with 1 alpha-OH-D3 appears to be of therapeutic value in metabolic bone disease associated with chronic renal failure, but frequent control of blood biochemistry seems mandatory.
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PMID:L-alpha-hydroxycholecalciferol treatment of adults with chronic renal failure. 96 64

Between 1969 and April 1975 24 patients with severe secondary hyperparathyroidism (sHPT) clinically presenting with uremic osteopathy required either total (n=5) or subtotal (n=18) parathyroidectomies, 17 patients were already supported by maintenance hemodialysis, 6 patients suffered from terminal renal insufficiency. The leading clinical symptoms consisted of general osteoporosis, spontaneous fractures, extraosseous calcifications and histologically proven dissecting fibroosteoclasia. After operation 18 patients experienced complete relief from their complaints and repair of their skeletal lesions, 2 patients required reexploration for an undetected hyperfunctioning 4th parathyroid gland, regretfully with no success. In 4 patients with subtotal parathyoidectomy a recurrence of varying intensity with increased PTH-secretion from the remnant had to be registered after months and years.-The indication for surgical treatment of sHPT due to chronic renal failure has to be based on two sets of findings: 1) inadequate longterm suppression of increased PTH secretion by conservative measures like high dialysate calcium concentration or oral calcium intake, serum phosphorus depletion by oral intake of aluminium hydroxyde and possibly also by Vit. D; 2) persistent hypercalcemia, progressive osteodystrophy and severe complaints like bone pain and pruritus.
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PMID:[Surgical aspects of secondary hyperparathyroidism (author's transl)]. 101 8

Osteodystrophy is almost universally present in chronic renal failure. Mild, but detectable, abnormalities--especially in parathyroid hormone (PTH) secretion--occur even when the glomerular filtration rate is greater than 30 cc/min. Osteomalacia is common in areas in which vitamin D intake and exposure to sunlight are minimal; when these factors are plentiful, osteitis fibrosa predominates. Osteoporosis is seen with increasing frequency in hemodialyzed patients. Nonosseous complications of secondary hyper-parathyroidism include hypercalcemia, metastatic calcification and pruritus. The most important factor in the medical therapy of osteodystrophy is control of serum phosphate levels. Next, a positive calcium balance must be provided either by giving vitamin D as dihyrdotachysterol, raising dialysate calcium or administering calcium orally. Parathyroidectomy is sometimes indicated, especially when the patients are transplant candidates and manifest hypercalcemia. Whether or not transplant is contemplated, patients with persistently high calcium-phosphate products, severe metastatic calcification or rapidly progressive osteodystrophy should be considered for parathyroidectomy. Newer, experimental vitamin D preparations, such as 1,25-dihydroxycholecalciferol or 1-alpha-hydroxycholecalciferol, should improve the managemet of patients with renal osteodystrophy and decrease the need for parathyroidectomies.
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PMID:Calcium metabolism in renal failure. 109 Jan 50

A radioimmunoassay for the measurement of immunoreactive parathyroid hormone (PTH) in human serum is described. The assay is based on the ability of human parathyroid hormone (h-PTH) to compete with 125I-labelled bovine parathyroid hormone (b-PTH) for binding to a guinea-pig antiserum directed against b-PTH. The linear part of the standard curve was parallel with dose response curves for anti-b-PTH serum reacting with dilutions of sera from patients with primary hyperparathyroidism and from h-PTH purified from human parathyroid adenomas, indicating that levels of immunoreactive PTH could be expressed as b-PTH equivalents. The range in 62 healthy blood donors was 1.1-2.5 ng b-PTH Eg./ml. The reproducibility was satisfactory, and the sensitivity permitted the measurement of PTH concentrations down to 0.8 ng b-PTH Eg./ml. No crossreaction with h-CT, h-STH or h-ACTH was observed. The clinical value of the assay has been considered in a number of patients with various disorders of calcium metabolism, diagnosed and treated conventionally. About 80 per cent of patients with primary hyperparathyroidism had elevated PTH levels on one or more occasions before surgery. In patients with chronic renal failure of other aetiology than primary hyperparathyroidism the levels were usually far higher. Patients with primary hyperparathyroidism and increased S-creatinine had higher PTH levels than those with normal S-creatinine. After parathyroidectomy all previously increased PTH levels became normal or low. High PTH concentrations were found in 3 patients with normocalcaemic hyperparathyroidism who at operation were shown to have parathyroid adenomas. However, in normocalcaemic patients there were also some falsely elevated PTH values which limit the diagnostic value of the assay in this group of patients. Low PTH values were observed in patients with hypercalcaemia due to malignant disorders, indicating that PTH determination may be of some value in the diagnosis of patients with hypercalcaemia of unknown origin.
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PMID:The diagnostic value of a radioimmunoassay for parathyroid hormone in human serum. 117 15

A radioimmunoassay for serum immunoreactive parathyroid hormone (iPTH), which has had widespread clinical use for five years, is described in detail. The iPTH results in large groups of patients are reported, and are discussed in relation to the specificity of the assay and in relation to other assays. The assay has excellent precision and is highly proficient in discrimination of groups of patients. Ninety-three percent of 412 patients with surgically proven primary hyperparathyroidism were confidently separated from normal subjects or patients with hypercalcemia owing to other causes, while 86 percent of 160 patients with chronic renal failure and secondary hyperparathyroidism had iPTH values more than 2 S.D. above the normal mean. Results in patients with ectopic hyperparathyroidism were lower than in primary hyperparathyroidism although these groups showed considerable overlap. The antiserum used in this assay for iPTH appears to be specific for the carboxy-terminal region of the secreted or intact form of PTH but recognizes predominantly the secreted form rather than carboxy-terminal fragments believed to be in the circulation. It does not recognize amino terminal fragments. The assay is useful in selective venous catheterization for preoperative localization of hyperfunctioning parathyroid tissue.
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PMID:Parathyroid hormone: radioimmunoassay and clinical interpretation. 118 Apr 81

The diagnosis of humoral hypercalcaemia of malignancy often presents considerable clinical problems. We have studied parathyroid hormone-related peptide (PTHrP) in serum from patients with humoral hypercalcaemia of malignancy (N = 22), hypercalcaemia of malignancy with skeletal metastases (17), histologically confirmed primary hyperparathyroidism (21) and hypercalcaemic patients with various benign diseases (9). PTHrP measurements were also made in normocalcaemic patients with various malignancies (23), endocrine diseases (13), sarcoidosis (22) and chronic renal failure (17). PTHrP was measured by a novel radioimmunoassay using rabbit antibodies directed towards the midregion of the molecule. Immuno- or silica cartridge extraction of serum before radioimmunoassay enabled us to measure PTHrP in all samples, which may add further information about circulating forms of PTHrP. PTHrP was clearly elevated in patients with humoral hypercalcaemia of malignancy (5.0 +/- 4.7 pmol/l) (mean +/- SD, N = 12) and when the kidney function was impaired (4.0 +/- 0.9 pmol/l) (N = 15) (silica cartridge extraction), whether the subject was hypercalcaemic or not. Some patients with endocrine diseases, including two with primary hyperparathyroidism, had slightly elevated serum PTHrP concentrations, while they were normal in sarcoidosis. In healthy subjects the levels were 1.1 +/- 0.5 pmol/l (N = 15) after immunoextraction and 0.8 +/- 0.2 pmol/l (N = 33) after silica cartridge extraction.
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PMID:Parathyroid hormone-related peptide, measured by a midmolecule radioimmunoassay, in various hypercalcaemic and normocalcaemic conditions. 144 40


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