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)

We describe an adult patient who developed persistent hypercalcemia while bedridden for more than three months with pancreatitis and sepsis. On the basis of hypercalciuria, suppressed serum intact PTH, suppressed serum 1,25-dihydroxy vitamin D3 and no clinical evidence of malignancy, the diagnosis of immobilization hypercalcemia was established His hypercalcemia improved during treatment with saline, calcitonin and/or etidronate. With active mobilization and weight-bearing exercises, serum calcium finally normalized. We discuss clinical and laboratory features as well as current modalities of treatment of this rare form of hypercalcemia in adults.
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PMID:Immobilization hypercalcemia in an adult patient with pancreatitis and sepsis: case report. 148 89

Thionaphthene-2-carboxylic acid (TNCA) has been shown to decrease osteoclast-mediated bone resorption in vitro and has shown efficacy in animal models of hypercalcaemia of malignancy. In this study, the effects of TNCA on the tibial proximal epiphysis and the sternum have been quantified by image analysis in rats administered the drug orally for 90 days at 75, 125 or 250 mg/kg/day. The amount of bone in the subepiphyseal area and sternum was increased in a dose-related manner. TNCA exerted a biphasic effect on the height of the epiphyseal plate. It was stimulatory at the low dosage and inhibitory at the high dose. This study constitutes the first of its kind to demonstrate the in-vivo effect of TNCA on the bones of rats.
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PMID:The effect of thionaphthene-2-carboxylic acid (TNCA) on bone structure in the rat: a histomorphometric study. 149 2

Hypercalcemia in hematological malignancy is frequently encountered in lymphoid malignancies such as adult T-cell leukemia (ATL) and multiple myeloma and is difficult to manage. As a causative agent of hypercalcemia in ATL, tumor necrosis factor-beta (TNF-beta), previously known as lymphotoxin, has been carefully studied and reviewed here. Bone resorption studies showed the presence of activity in culture supernatants of HTLV-I infected cells. Enzyme linked immunosorbent assays (ELISA) for TNF-beta detected elevated TNF-beta in the sera of ATL patients with hypercalcemia. Immunostaining by monoclonal anti-TNF-beta antibody demonstrated the presence of TNF-beta in both HTLV-I infected cell lines and freshly isolated ATL cells. Furthermore biological TNF-beta activity assay including inhibition of anti-TNF-beta antibody confirmed the conventional documentation of TNF-beta activity in the sera and culture supernatants of HTLV-I infected cell lines. These studies showed that the TNF-beta secreted from ATL cells might be one of the factors contributing to the hypercalcemia in patients with ATL functioning as an osteoclast activating factor (OAF).
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PMID:Tumor necrosis factor-beta and hypercalcemia. 149 42

Tumor-induced hypercalcemia and tumor-induced osteolysis are essentially due to a marked increase in osteoclast-mediated bone resorption, although the kidneys play an important contributory role in the genesis of tumor-induced hypercalcemia. Parathyroid hormone-like protein plays an essential role in tumor-induced hypercalcemia, and maybe in tumor-induced osteolysis, but other factors could also be responsible for the osteoclast activation secondary to the neoplastic infiltration of the skeleton. Treatment of tumor-induced hypercalcemia essentially consists of volume repletion and administration of potent anti-osteolytic drugs. The bisphosphonate pamidronate is particularly useful for that matter and a dose of 1.0 to 1.5 mg/kg can normalize serum calcium in about 90% of hypercalcemic cancer patients. The apparently low response rate of bone metastases to systemic antineoplastic therapy seems to essentially reflect the relative insensitivity of our current methods for assessing response in tumor-induced osteolysis. Newly developed biochemical markers of bone turnover could be particularly useful for that matter. Bisphosphonates are the most potent of the available inhibitors of osteoclast activity. Prolonged administration of oral pamidronate could reduce by almost one half the complications of tumor-induced osteolysis, and repeated bisphosphonate infusions could induce a dramatic relief of bone pain in one third and a sclerosis of lytic lesions in one fourth of the cases. These data must, however, be confirmed in randomized, blinded trials and many questions remain unanswered concerning the optimal therapeutic schemes. Medical therapy of tumor-induced osteolysis by noncytotoxic means has nevertheless become a reality.
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PMID:Bone metastases and tumor-induced hypercalcemia. 151 Oct 19

The ultrastructure of parathyroid chief cells was examined from four groups of nude mice (NIH:Swiss) with different serum calcium concentrations. The groups consisted of eight male mice with hypercalcemia induced by transplantable canine adenocarcinoma (CAC-8), eight female mice with hypercalcemia induced by infusion of parathyroid hormone-related protein, ten male control mice, and six male mice fed a low calcium (0.01%) diet. Hypercalcemia induced by malignancy or parathyroid hormone-related protein infusion was associated with low serum phosphorus concentration, a decrease in the number of secretory and prosecretory granules in the parathyroid chief cells, and an increase in the cytoplasmic area of chief cells. Prominent myelinlike membranous whorls were present in the cytoplasm of chief cells of tumor-bearing and parathyroid hormone-related protein-infused hypercalcemic mice. Mice fed a low calcium diet had decreases in the number of secretory granules and cell area but increases in the number of prosecretory granules compared with control mice. The number of mitochondria and the nuclear area of chief cells were similar in all four groups. The prominent membranous whorls and increased cytoplasmic area of chief cells from these hypercalcemic mice mark these cells as distinctly different from the parathyroid chief cells of other species with hypercalcemia.
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PMID:Effects of humoral hypercalcemia of malignancy on the parathyroid gland in nude mice. 151 21

Hypercalcaemia frequently complicates the clinical management of cancer. Many factors have been implicated in the pathogenesis of this humoral hypercalcaemia of malignancy, the most recent candidate being parathyroid hormone-related peptide (PTHrP). Until now, this peptide has been detected only in some normal and transformed adult tissues. In recent years, it has become apparent that tumours are capable of expressing and secreting factors previously elaborated only during fetal life. Many of these factors act to stimulate the growth of both tumour and fetal cells in an autocrine manner. The data presented here demonstrate that PTHrP is expressed in the human and rat fetus throughout gestation. Immunocytochemistry reveals a gestationally related, changing pattern of expression which is paralleled by changes in mRNA transcription. These data support the hypothesis that PTHrP may function as a fetal growth factor.
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PMID:Parathyroid hormone-related peptide: expression in fetal and neonatal development. 151

More than one million Americans will be diagnosed with cancer during 1992, and 50% will be cured of their disease. Of those individuals not cured of the malignancy, survival time after diagnosis has increased tremendously compared to 1980. Because of advances in therapy and the increase in long-term survival, the presence of cancer patients in critical care units should no longer represent either a medical contradiction or an ethical dilemma when the condition requiring critical care is potentially reversible. Many of these individuals may become patients in critical care settings as a result of specific electrolyte imbalances caused by the malignant disease or treatment of malignancy. Although the imbalances often are temporary, they can be life-threatening without intervention. The most common temporary electrolyte imbalances associated with malignant conditions are hypercalcemia, hyperkalemia, and tumor lysis syndrome. Critical care nurses can contribute skill and knowledge in ameliorating these conditions so that the person with cancer can have better quality and longer survival time.
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PMID:Common electrolyte imbalances associated with malignancy. 152 43

Hypercalcemia may occur as a complication of haematological malignancies, in association with solid tumors with bone metastases, and with solid tumors in the absence of bone metastases. The latter syndrome, known as the humoral hypercalcemia of malignancy (HHM) shares many features with primary hyperparathyroidism. A parathyroid hormone-related protein (PTHrP) has been identified, isolated and cloned, which is most likely responsible for the calcium disturbances in HHM, PTHrP is a previously unrecognized hormone which has limited amino-terminal sequence homology with PTH and is the product of a separate gene. Tissue localization studies have identified PTHrP in squamous cell carcinomata, renal cortical carcinomata, in a proportion of breast cancers and in adult T-cell leukemia/lymphoma. In normal tissues, PTHrP has been immunohistochemically localized in keratinocytes, placenta and fetal parathyroid glands. In addition to its role in mediating hypercalcemia in cancer, PTHrP is likely to have an important endocrine role in the fetus, and perhaps a paracrine function in several organs.
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PMID:Hypercalcemia in cancer. 152 53

The recent advances in molecular biology and cytogenetics have made it possible to localize, clone and characterize some of the genetic abnormalities which result in disorders of phosphate and calcium homeostasis. Thus, the genes causing X-linked hypophosphataemic rickets, Lowe syndrome, X-linked recessive hypoparathyroidism, Di George syndrome, multiple endocrine neoplasia type 1, multiple endocrine neoplasia type 2 and vitamin D-dependent rickets type I have been mapped. In addition the genes involved in the pathogenesis of the humoral hypercalcaemia of malignancy, vitamin D-dependent rickets type II, pseudohypoparathyroidism, and some of the autosomal forms of hypoparathyroidism have been cloned and the mutations characterized. The molecular and genetic studies which have mapped and identified these disease genes are described and the implications of these developments in clinical practice and in further elucidation of the mineral metabolic defects are discussed.
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PMID:Molecular genetics of mineral metabolic disorders. 152 19

Among aminohydroxybisphosphonate derivatives, alendronate (3-amino-1-hydroxybutylidene-1,1-bisphosphonate) has proved efficacious in diseases with increased bone resorption. However, the effective dose in the treatment of malignant hypercalcemia is not clearly established. In 2 randomized studies, we investigated the effects of alendronate and of clodronate (dichloromethylene bisphosphonate) given as a single infusion in 82 rehydrated patients with malignant hypercalcaemia. Various doses of alendronate or clodronate soon produced a significant fall in plasma calcium (Ca), accompanied by a dose-dependent decrease in the fasting urinary Ca/creatinine ratio, taken as a reflection of bone resorption. During the next 5 days, plasma Ca and fasting urinary Ca/creatinine ratio were lower in the group treated with alendronate than in the clodronate group. The renal handling of Ca was similar in both groups. Because of relapsing hypercalcaemia, some patients received an infusion of alendronate approximately 2 weeks after the first infusion; this normalized the urinary Ca/creatinine ratio in 44% of the cases at day 3. At that time, the plasma Ca was below 2.70 mmol/l in 33%. Our results indicate that alendronate decreased bone resorption and calcaemia in cancer patients in a dose-dependent manner.
Int J Cancer 1992 Mar 12
PMID:Effect of a single infusion of alendronate in malignant hypercalcaemia: dose dependency and comparison with clodronate. 153 72


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