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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ratio of reabsorption of osmotically free water to osmolal clearance in individual urine voids was about the same before and after short-term spaceflights (the points fall on the same regression line). This ratio was reduced after long-term flights, so that the regression lines for pre- and postflight values have different slopes. This change in the function relating the two factors was accompanied by increased vasopressin in blood plasma and probably was caused by altered cellular reaction to vasopressin. The decrease in the effect of vasopressin may have been caused by development of hypokalemia and hypercalcemia in the cosmonauts, and decrease in cellular potassium in the outer renal medulla (this effect was observed in experiments on rats after flights on biosatellites). We established that, in addition to cAMP, cGMP and inositol trisphosphate participate in cellular reactions to vasopressin. Increases in the concentration of cGMP and decrease in the formation of inositol trisphosphate in the presence of neomycin increase the hydro-osmotic effect of vasopressin. We hypothesize that modulation of the effect of vasopressin in cosmonauts is due to change in the functional state of their kidneys.
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PMID:Mechanism of postflight decline in osmotic concentration of urine in cosmonauts. 166 Feb 60

Hypercalcemia occurring in a patient with an islet cell carcinoma of the pancreas suggests the diagnosis of Multiple Endocrine Neoplasia Type I and associated hyperparathyroidism. We describe a patient with an islet cell carcinoma and hypercalcemia in whom low concentrations of PTH, the absence of skeletal metastases, hypophosphatemia, and elevated nephrogenous cAMP alternatively suggested the syndrome of humoral hypercalcemia of malignancy. The peptide PTHrP was measured in the patient's serum during the course of therapy by an immunoradiometric assay directed toward the midportion of the molecule. Hypercalcemia was treated with an investigational aminobisphosphonate. The concentration of PTHrP[56-86] increased over time and fell after the patient received chemotherapy directed toward the islet cell tumor.
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PMID:Parathyroid hormone-related peptide mediates hypercalcemia in an islet cell tumor of the pancreas. 166 81

Parathyroid hormone (1-34) [PTH-(1-34)] has been shown to stimulate sodium-dependent phosphate transport (NaPiT) in UMR-106 osteoblast-like cells through a cAMP-dependent mechanism. Whether a synthetic amino-terminal fragment of parathyroid hormone-related protein (PTHrP) or the full-length molecule, which are recognized to interact with the same receptor as PTH, affect NaPiT in the same way is not known. We investigated and compared the effects of bPTH-(1-34), PTHrP-(1-34), and PTHrP-(1-141) on NaPiT and cAMP production in the osteoblastic cell line UMR-106. Each of the three peptides increased cAMP production and exerted a concentration-dependent stimulation of NaPiT after incubation for 4-6 h. We also studied the effect of transforming growth factor-alpha (TGF-alpha), which is another tumoral product secreted by certain hypercalcemia-associated tumors, on NaPiT and the TGF-alpha-induced modulation of the response to PTHrP or PTH. TGF-alpha caused a 30% stimulation of NaPiT, which remained stable from 6 to 24 h, by a cAMP-independent mechanism. In contrast, TGF-alpha attenuated cAMP production stimulated by PTH, PTHrP-(1-34), or PTHrP-(1-141). PTHrP or PTH did not further increase NaPiT in TGF-alpha-treated cells. These results indicate that NaPiT, a possibly important function of osteoblastic cells, was similarly affected by PTH and PTHrP. TGF-alpha increased NaPiT and modulated in a similar way the effects of both PTH and PTHrP.
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PMID:Stimulation by parathyroid hormone-related protein and transforming growth factor-alpha of phosphate transport in osteoblast-like cells. 166 9

Influence of vasoactive intestinal polypeptide, neuropeptide Y, calcitonin gene-related peptide, and substance P was investigated on dispersed parathyroid cells of adult cattle. At a physiological concentration of extracellular calcium, vasoactive intestinal polypeptide stimulated the parathyroid hormone release in a dose-dependent manner, whereas no effects were noted for the other peptides. The dependency of PTH secretion upon extracellular calcium was shifted to the right by vasoactive intestinal polypeptide at 10(-6) mol/l, with a tendency for greater effects at low (0.5 mmol/l) than high concentrations (2.0-3.0 mmol/l) of the cation. Vasoactive intestinal polypeptide significantly enhanced cAMP release of the parathyroid cells, whereas no influence was noted on cytoplasmic calcium or pH within the cells. The results suggest that vasoactive intestinal polypeptide stimulates the PTH release by interaction with cAMP production of the parathyroid cells. This effect may contribute to the development of hypercalcemia in patients with neuroendocrine tumours secreting vasoactive intestinal polypeptide.
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PMID:Vasoactive intestinal polypeptide stimulates parathyroid hormone release by interaction with cyclic adenosine monophosphate production of bovine parathyroid cells. 170 45

Plasma concentrations of PTH are much lower for a given calcium or phosphorus level in patients with familial benign hypercalcemia (FBH, or familial hypocalciuric hypercalcemia) than in those with primary hyperparathyroidism; these and other data suggest that there might be tissue hypersensitivity to PTH in FBH. To test this hypothesis, we have used cultured dermal fibroblasts from abdominal skin biopsies of six patients with FBH and six age- and sex-matched controls as surrogate PTH-responsive tissues. Cells in 24-well plastic plates were exposed to vehicle, human PTH-(1-34) (10(-10)-10(-7) M), prostaglandin E2 (10(-6) M), or isoproterenol (10(-4) M) for 10 min in the presence of isobutylmethylxanthine, and cellular cAMP was determined by RIA. All cells responded to PTH with dose-dependent increases in cAMP, and all responded strongly to prostaglandin E2 and isoproterenol. There were no consistent or significant differences between control and FBH fibroblasts in maximal responses to the three agonists, and half-maximal stimulation was achieved with about 10(-9) M PTH in both normal and FBH cells. These data are not consistent with increased tissue sensitivity to PTH in FBH.
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PMID:Cyclic adenosine 3',5'-monophosphate responses to parathyroid hormone, prostaglandin E2, and isoproterenol in dermal fibroblasts from patients with familial benign hypercalcemia. 171 Jun 22

Primary hyperparathyroidism (PHPT) is characterized by hypersecretion of parathyroid hormone (PTH) leading to hypercalcemia and relative hypophosphatemia. PTH acts by binding to cell surface receptors coupled to G proteins. Cyclic AMP is the classic second messenger of PTH action, but substantial evidence indicates that PTH also acts to stimulate formation of the dual second messengers, inositol trisphosphate and diacylglycerol, thereby mobilizing intracellular calcium. The physiologic actions of PTH include (1) an increase in extracellular fluid ionized calcium through direct actions on kidney and bone, the classic target organs for PTH, and (2) a decrease in extracellular fluid phosphate primarily through renal action. The pathophysiologic effects of PTH arise from (1) direct actions of PTH on bone and kidney, and possibly on nonclassic target organs, and (2) indirect effects of altered mineral homeostasis. PTH hypersecretion in PHPT can lead to bony demineralization, nephrolithiasis, and hypercalcemic crisis. PHPT may also be associated with mental disturbances, neuromuscular disease, hypertension, and glucose intolerance.
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PMID:Pathophysiology of primary hyperparathyroidism. 176 67

Pamidronate has been demonstrated to be an effective agent in the treatment of cancer-associated hypercalcaemia. The dose regime, however, remains controversial. In this study 16 patients with cancer-associated hypercalcaemia were given 30 mg pamidronate by intravenous infusion and 16 were given 90 mg also by infusion. Groups were well-matched in terms of tumour types, bone metastases, pre-treatment serum calcium and creatinine, fasting urinary calcium/creatinine ratio, nephrogenous cAMP and the renal tubular threshold for phosphate reabsorption (TmPO4). The calcium lowering effect was similar in both treatment groups with nadir at day 6 of mean (+/- SEM) 2.48 mmol/l (+/- 0.06) in the 30 mg group and at day 9 in the 90 mg group of 2.51 mmol/l (+/- 0.03) (P less than 0.01). 10 patients in the 30 mg group and 8 in the 90 mg group were normocalcaemic at this point. Similarly when those patients with more severe hypercalcaemia (greater than 3.30 mmol/l, n = 7 in each group) were analysed separately, no significant difference was evident between the two groups. Urinary calcium/creatinine ratios fell to a nadir at day 6 in both groups of 0.33 (+/- 0.05) (30 mg group) and 0.37 (+/- 0.10) (90 mg group) (P less than 0.01). Follow-up results after the initial 9 days showed the mean time to relapse to be 38 days (range 18-90) in the 30 mg group and 34 days (11-105) in the 90 mg group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A comparison of low versus high dose pamidronate in cancer-associated hypercalcaemia. 177 37

It has been controversial whether increased renal tubular calcium reabsorption contributes to hypercalcemia in patients with malignancies. Moreover, whether this abnormality is associated with volume depletion, a parathyroid hormone-like effect, or other mechanisms has not been clarified. Eight consecutive patients with hypercalcemia due to a variety of tumor types were studied in detail. The glomerular filtration rate (iothalamate clearance) was reduced in all patients (0.98 +/- 0.10 (mean +/- SE) mL/s.1.73 m2; P less than 0.001) compared with normal controls (N = 9) (1.93 +/- 0.08 mL/s.1.73 m2), but it was similar to that in controls matched for renal insufficiency (N = 6) (1.15 +/- 0.05 mL/s.1.73 m2). During hypercalcemia produced by calcium infusion, urinary calcium excretion (millimoles of calcium per liter of glomerular filtrate) was increased in controls with renal insufficiency compared to those with normal renal function (P = 0.028). In all patients with hypercalcemia of malignancy, urinary calcium excretion was decreased compared with controls with renal insufficiency, but it was low in only five of eight patients compared with normal controls. Extracellular fluid volume (iothalamate volume of distribution) was not decreased in any patient, and urinary cAMP and/or plasma parathyroid hormone-like bioactivity were increased in six of eight patients. After treatment with an inhibitor of bone resorption, aminopropylidene 1,1 diphosphonate, abnormal renal calcium handling was not detected if the serum calcium normalized. It was concluded that increased renal tubular calcium reabsorption was consistently present in patients with hypercalcemia of malignancy compared with controls matched for renal insufficiency, but the proportion with the abnormality was underestimated if normal controls were used.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Altered renal calcium handling in hypercalcemia of malignancy. 195 31

The roles of parathyroid hormone (PTH) and calcitonin (CT) in the pathogenesis of familial benign hypercalcemia (FBH, or hypocalciuric hypercalcemia) are uncertain. Thus we performed studies in 26 patients with FBH, 12 patients with primary hyperparathyroidism (HPT), and 20 normal volunteers, to answer these questions: are plasma levels of intact or biologically active PTH frequently elevated in FBH? Is plasma intact PTH nonsuppressible during calcium infusion? Is there blunting of the C cell CT response to calcium infusion as occurs in primary HPT? We used three methods for measurement of PTH: a mid region-specific radioimmunoassay (iPTH, antiserum GP-1M), an extraction-concentration bioassay (bioPTH, stimulation of cAMP generation in osteoblastlike cells), and a two-site immunoradiometric assay (IRMA) for intact PTH. PTH levels were significantly elevated in primary HPT by all three methods, but mean PTH was normal in FBH and 85-92% of values overlapped the normal range. During 5 minute calcium infusions (2 mg Ca2+ per kg) iPTH values fell little, but bioPTH and intact PTH fell sharply in all three groups. Mean calcium-induced decreases of intact and bioPTH were indistinguishable from normal in FBH, but PTH levels generally remained elevated at 5 minutes in primary HPT. In FBH basal and postinfusion CT levels were normal. The data show that, in the majority of patients with FBH, PTH concentrations and bioactivity in blood are within the normal range and are suppressed rapidly to very low levels with further increases of calcium. The data suggest that the abnormality of parathyroid function in FBH differs from that in primary HPT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calcium regulation of parathyroid and C cell function in familial benign hypercalcemia. 202 33

In two patients suffering from hypoparathyroidism (HP) whose serum calcium and -phosphate could not be normalized with Vitamin D3-resp. Calcitriol and who continued to have tetanic convulsions, synthetic 1-38 human parathyroid hormone (1-38 hPTH) was used for treatment. In both patients the intravenous administration of 1-38 hPTH provoked a rapid increase of phosphaturia and cAMP-excretion and an increase of the serum calcium level into the normal range. The same effects, only slightly delayed, could be achieved with subcutaneous injections which the patients had learned to do themselves. In case 1, a boy aged 14 years with autoimmune-HP, the daily administration of 8.5 U/kg BW caused hypercalcemia on the 6th day of treatment; therefore the dosis was reduced to alternate day administration. In case 2, a girl aged 17 1/2 years with idiopathic HP, treatment was started with alternate day administration (7.7 U/kg BW/day of injection); serum calcium increased to levels of about 2.2 mmol/1. Side effects could not be seen. Case 1, however, developed resistance to 1-38 hPTH after 10 weeks of therapy. 1-38 hPTH can be classified as an effective substance in the treatment of HP. Optimal dose and frequency of administration cannot yet be pointed out.
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PMID:[Initial experiences with substitution treatment of hypoparathyroidism with synthetic human parathyroid hormone]. 216 6


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