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

Five patients with haemodialysis bone disease were treated with 1 to 1.5 mug of 1,25 (OH)2D3 daily for periods ranging from 6 -8 months. There was a significant improvement in calcium absorption but no troublesome hypercalcaemia was encountered. Secondary hyperparathyroidism improved, both histologically and radiologically, and there was a fall in serum PTH and return of serum alkaline phosphatase to within normal limits. There was also improvement in the patients' mineralisation status, but this change was slower and less marked. Muscle power improved significantly, both clinically and electromyographically.
 ...
PMID:Long term therapy with 1,25(OH)2D3 in dialysis bone disease. 93 16

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.
 ...
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.
 ...
PMID:[Surgical aspects of secondary hyperparathyroidism (author's transl)]. 101 8

The assay of parathyroid hormone has contributed greatly to our understanding of calcium metabolism in health and disease. The most important clinical application of the assay is in the differential diagnosis of hypercalcaemia, which is an increasing clinical problem. PTH assays are of little or no value in the absence of other biochemical data, especially accurate determinations of plasma calcium and phosphate.
 ...
PMID:Assay of parathyroid hormone in human serum and its uses. 101 86

We studied a patient with acute myeloblastic leukemia, hypercalcemia, hypophosphatemia and inappropriately elevated serum parathyroid hormone levels to define the mechanism of the hypercalcemia. On six occasions during two years, hypercalcemia occurred in conjunction with relapses of leukmia. Each time, serum calcium decreased to normal levels in parallel with reduction of the leukemic mass. During two periods of hypercalcemia, immunoreactive parathyroid hormone values were abnormally high. In addition, hormone was detected in vitro after short-term incubation of the leukemic cells (after 24 hours, the patient's cells produced 129 pg of PTH per milliliter, whereas myeloblasts from a normocalcemic patient with leukemia produced only 33 pg). In freeze-thawing experiments, 39 pg of parathyroid hormone was released form 1 x 108 of the patient's myeloblasts; no hormone was released from the normocalcemia cells. These findings suggest that the hypercalcemia resulted from ectopic parathyroid hormone production by leukemic cells.
 ...
PMID:Acute myelobalstic leukemia and hypercalcemia. A case of probable ectopic parathyroid hormone production. 106 24

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.
 ...
PMID:Parathyroid hormone: radioimmunoassay and clinical interpretation. 118 Apr 81

The gene encoding PTH-related peptide (PTHrP) is expressed in a wide variety of normal and neoplastic tissues. Increased PTHrP gene expression in and secretion of PTHrP by specific tumors directly contributes to the development of malignancy-associated hypercalcemia in vivo. To define the genetic elements important for the control of PTHrP gene transcription, we used the reverse transcription polymerase chain reaction to delineate the control of promoter utilization and the splicing patterns of the exons encoding 5'-untranslated sequences. The majority of normal and neoplastic human tissues contained PTHrP mRNA transcripts initiating from both the up-stream (P1) and down-stream (P2) human PTHrP promoters. Furthermore, the downstream promoter was preferentially used by a factor of more than 30-fold. P1-initiated transcripts contained RNA species both with and without exon 2 (E2) sequences, except in the pancreas, adrenal, and stomach, where E2-containing sequences predominated. The transcriptional activities of P1, P2, and P1 + P2 were assessed by transfection of the corresponding PTHrP-chloramphenicol acetyltransferase (CAT) fusion genes into heterologous cell lines. Fusion genes containing P2 sequences were more transcriptionally active than fusion genes containing P1 sequences. The transcriptional activities of P1 + P2 in their natural tandem orientation were additive in rat keratinocytes and human JEG choriocarcinoma cells. In contrast, the activity of P1 + P2 was less than that of P2 alone in hamster BHK fibroblasts and InR1-G9 cells, and human HeLa cells. Analysis of the transcriptional properties of 5'-deleted human PTHrP-CAT constructs revealed the presence of multiple positive and negative DNA sequences (within both P1 and P2) functionally important for human PTHrP gene transcription. Distinct positive and negative DNA elements were also identified from analysis of 5'-deleted rat PTHrP-CAT fusion genes. The results of these experiments provide evidence for cell- and tissue-specific utilization of 1) distinct human PTHrP transcription start sites and specific patterns of 5'-exon splicing and 2) multiple positive and negative DNA control elements, important for the regulation of human and rat PTHrP gene transcription.
 ...
PMID:Regulation of parathyroid hormone-related peptide (PTHrP) gene transcription: cell- and tissue-specific promoter utilization mediated by multiple positive and negative cis-acting DNA elements. 128 Mar 27

A patient with acute primary hyperparathyroidism treated with mithramycin preoperatively, underwent neck exploration and two enlarged parathyroid glands were excised: one huge adenoma (6g) and another smaller gland. Mithramycin was administered preoperatively to lower life-threatening hypercalcaemia, and parathyroid slices from the huge adenoma removed at surgery were submitted in vitro to various calcium concentrations in the media to determine the influence of calcium on parathyroid adenoma secretory pattern in acute primary hyperparathyroidism. Mithramycin induced a significant decline in calcium levels and significant elevations of calciotrophic hormones (intact PTH, mid-region specific PTH, calcitonin and calcitriol). Significant suppression in PTH output in vitro was achieved by increasing calcium levels in the media. These results exclude autonomous PTH secretion (non-calcium dependent) as a possible aetiology of acute primary hyperparathyroidism. We suggest that a sudden increase in the set-point of the diseased parathyroid cells in the presence of a huge cell mass accounts, in large part, for both the marked hypercalcaemia and elevated PTH levels in this patient.
 ...
PMID:Non-autonomy of parathyroid hormone secretion in acute primary hyperparathyroidism. 128 27

Four young milk-fed calves were fitted with catheters chronically implanted in the mesenteric, portal and hepatic veins and in the hepatic artery. Electromagnetic blood flow probes in the portal vein and hepatic artery allowed continuous measurement of hepatic IGF-1 production. In accordance with a latin square design these calves received iv mesenteric infusion (for 60 min) of calcium (Ca, 0.125 mmol.kg body wt-1), the synthetic human parathyroid hormone-related protein (1-34) fragment (PTHrP, 1 nmol.kg body wt-1), the synthetic analogue [tyr]34-bovine PTH-(7-34) NH2 (2 nmol.kg body wt-1) and PTHrP (1 nmol.kg body wt-1) or solvent alone (1.2 ml.kg body wt-1). Hypercalcaemia observed following Ca infusion had no significant effect on hepatic IGF-1 production. PTHrP induced a slight but significant increase in plasma Ca and IGF-1 concentrations measured in the hepatic vein, without changing blood flows measured in the hepatic artery and portal vein. Thus PTHrP increased hepatic IGF-1 production (15.1 +/- 2.7 nmol.6 h-1.kg body wt-1 vs 4 +/- 1.3 nmol.6 h-1.kg body wt-1 in controls; p less than 0.05). These effects induced by PTHrP were inhibited by the synthetic analogue [tyr]34-bPTH-(7-34) NH2.
 ...
PMID:The influence of parathyroid hormone-related protein on hepatic IGF-1 production. 130 83

The overproduction of hormones is associated with a variety of endocrinological disorders. We have used somatic cell gene transfer of human PTH (hPTH) to develop an animal model of hypercalcemia and osteoclastic skeletal resorption. Recombinant retroviruses were used to transduce a functional hPTH gene into cultured rat fibroblasts. The recombinant-derived preproparathyroid hormone peptide was appropriately processed in this ectopic cell, and intact hPTH (1-84) was secreted at a high level (2-5 ng/10(6) cells/24 h). Transplantation of the PTH-secreting cells into syngeneic rat recipients was associated with the development of hypercalcemia mediated by increasing serum concentrations of hPTH. Thyroparathyroidectomy in these hypercalcemic rats producing hPTH did not result in hypocalcemia and tetany, which was observed in control animals undergoing thyroparathyroidectomy. Chronic overproduction of hPTH (60 days) was associated with severe hypercalcemia, metastatic calcification, and histological changes of osteoclastic resorption of bone. This animal model will be useful in studying the pathophysiology of severe hyperparathyroidism in humans and should help in the evaluation of new medical therapies for hypercalcemia.
 ...
PMID:Somatic gene transfer in the development of an animal model for primary hyperparathyroidism. 131 63


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>