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

Slices of the thyroid gland were impregnated with silver nitrate and stained with hematoxylin. Separate calculation of the index of calchicin mitosis of the follicular and parafollicular (C-) cells was made. The material of 37 mature albino rats was analyzed. Calcium-rich diet was given to 22 animals during 10 days. Different levels of hypercalcemia were achieved by different doses of vitamin D2 (from 1 to 10 thousand MU daily, 11 experimental groups). The mitotic index of C-cells was found to grow but under mild hypercalcemia (10% of the control level). Further elevation of the calcium concentration in blood was followed by a decrease of the amount of the dividing parafollicular cells down to control values. In rats fed by the diet optimal for the stimulation of C-cells division (11 rats, 2000 MU as a daily dosage of vitamin D2) within the interval from 1 to 10 days increased mitotic activity of the follicular cells was found from the 3rd day, while that of C-cells only as late as the 9th-10th day. In all the experimental rats the mitotic index of the follicular thyrocytes was 3.5-4 times as high as the mitotic index of C-cells. Relatively not high proliferative activity of parafollicular cells might be due to their pronounced polyfunctional character and their participation in complex paracrine interactions with other cell elements of the thyroid gland.
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PMID:[The mitotic activity of the follicular and parafollicular (C) cells in the thyroid of rats with hypercalcemia]. 134 63

Important new information has been gained concerning the etiology of cancer-related hypercalcemia and thus treatment recommendations are changing. The most common cause of hypercalcemia in cancer patients is the parathyroid hormone-like peptide, PTH-RP. Patients with elevated serum calcium due to elaboration of parathyroid hormone-like peptide commonly present with hypophosphatemia and a relatively resistant form of hypercalcemia. Our new knowledge has led to recommendations against massive amounts of IV fluids and large doses of diuretics, which restore normocalcemia in only a minority of patients. New potent drugs such as pamidronate and gallium nitrate directly inhibit accelerated bone resorption. Thus, consideration should be given to the early administration of antiresorptive drugs immediately after intravascular volume has been repleted and urinary output has been established.
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PMID:Etiology and current management of cancer-related hypercalcemia. 139 13

Gallium nitrate lowers the serum calcium in patients with hypercalcemia caused by malignancy and is available for clinical use. The mechanism for the hypocalcemic action is unknown, however. The present studies were undertaken to determine the effects of gallium on bone metabolism. Normal male rats were implanted subcutaneously with mineralized allogeneic bone matrix. Histomorphometry of the implants and of tibiae was determined after three doses of tetracycline administered at intervals of 1 week. Gallium as nitrate was administered daily by intraperitoneal injection at doses of 0.9, 1.8, and 3.6 mg elemental gallium per kg body weight for 21 days in one study and at 3.5 mg/kg for 33 days in a second study. All the gallium-treated rats gained weight. Rats given gallium at doses of 3.5 mg/kg or more grew at a lower rate than untreated controls (-7 and -10% at doses of 3.5 and 3.6 mg/kg, respectively; p less than 0.05). At a dose of 0.9 mg/kg, gallium did not inhibit bone resorption or lower serum calcium but inhibited bone formation by 32% and bone apposition by 36% at the endosteal surface of the tibia. At a dose of 1.8 mg/kg, gallium produced modest hypocalcemia, prevented a rise in circulating 1,25-dihydroxyvitamin D [1,25-(OH)2D], inhibited bone resorption in implants, and inhibited bone formation by 19% and bone apposition by 18%. At a dose of 3.5 mg/kg, gallium lowered the serum calcium and serum 1,25-(OH)2D, inhibited growth, and accentuated the antiresorptive and antiformative effects seen at the two lower doses.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of gallium on bone in the rat. 154 54

Gallium nitrate, a novel drug for the treatment of cancer-related hypercalcaemia, inhibits osteoclast activity but does not affect osteoclast morphology or viability. Limited clinical experience in patients with cancer-related hypercalcaemia indicates that gallium nitrate is effective in restoring normocalcaemia in 75 to 85% of patients and is well tolerated in those with preserved renal function, producing few clinically relevant adverse effects. In comparative clinical trials it proved a more effective antihypercalcaemic agent than calcitonin or etidronate and produced a longer lasting normocalcaemic response. Gallium nitrate would appear to be indicated in symptomatic patients with cancer-related hypercalcaemia who have failed to respond to adequate rehydration.
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PMID:Gallium nitrate. A review of its pharmacological properties and therapeutic potential in cancer related hypercalcaemia. 171 24

The incidence of parathyroid carcinoma in patients surgically treated for primary hyperparathyroidism at the University of Michigan Hospital was 0.4% during an 18-year period. The courses of the five patients with metastatic disease are described. Histologic reevaluation and assessment of the DNA ploidy pattern were performed in each case. Localization studies preceded all reexplorations. The number of operative procedures in each patient ranged from two to 10. Two patients are living with recurrent disease and one has been disease free for 42 months. Two patients died after 2 and 12 years, respectively. Three patients had aneuploid tumors; one had a diploid tumor. One patient had both aneuploid and diploid cell populations. Dilemmas in diagnosis, localization, and medical and surgical management were encountered in patients with metastatic carcinoma. The chosen treatment should be evaluated individually in each case because of the variability in aggressiveness of this malignancy. Surgical resection proved most effective in some of these patients for both local and distant recurrences. Bisphosphonates and gallium nitrate have been reported to be effective in controlling hypercalcemia. Only the former had some effect in one of our patients.
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PMID:Metastatic parathyroid carcinoma: dilemmas in management. 174 86

Four cases of metastatic calcification due to hypercalcemia in adult T-cell leukemia-lymphoma (ATLL) are reported. Serum calcium was at high levels, 15.4-19.4 mg/dl (normal range 8.4-10.4 mg/dl). In our cases, metastatic calcification was detected by v. Kossa's silver nitrate method for calcium in tubules of kidneys (100%), pulmonary alveolar septa of lungs (100%), myocardium (75%), muscular layer of stomach (50%), lower portion of aortic media (50%), gastric mucosa (25%), testicular tubules (25%), and in the liver (25%). Scattered osteoclasts were seen around the cortex of the bone. Therefore, hypercalcemia in ATLL may have been caused by bone-resorption-stimulating factors which promote differentiation of osteoclast cells, resulting in calcium increase in the serum.
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PMID:Metastatic calcification due to hypercalcemia in adult T-cell leukemia-lymphoma (ATLL). 176 85

Hypercalcemia is a major source of morbidity and mortality in patients with cancer. Gallium nitrate and the bisphosphonate, etidronate, are new agents that have recently become available for treatment of this disorder. To directly compare therapeutic effectiveness, we conducted a randomized, double-blind, multicenter study of gallium nitrate compared with etidronate for acute control of cancer-related hypercalcemia. Gallium nitrate was administered by continuous intravenous (IV) infusion at a dose of 200 mg/m2/d. Etidronate was administered as a 4-hour IV infusion at a dose of 7.5 mg/kg. Both drugs were given daily for 5 consecutive days. Eligible patients had persistent moderate-to-severe hypercalcemia (total serum calcium [corrected for serum albumin] greater than or equal to 12.0 mg/dL) after 2 days of hospitalization and IV hydration. Seventy-one patients were randomized and treated. Twenty-eight of 34 patients (82%) who received gallium nitrate achieved normocalcemia compared with 16 of 37 patients (43%) who received etidronate (P less than .001). Patients who received etidronate required significantly greater amounts of IV fluids (P = .04) and more hypocalcemic drug treatment (P less than .05) during the poststudy period than patients who received gallium nitrate. Kaplan-Meier analysis showed a significantly longer median duration of normocalcemia for patients treated with gallium nitrate (8 days v 0 days, P = .0005). A significantly higher proportion of patients treated with gallium nitrate developed asymptomatic hypophosphatemia compared with patients treated with etidronate (97% v 43%, P less than .001). We conclude that gallium nitrate is highly effective and superior to etidronate for acute control of moderate-to-severe cancer-related hypercalcemia.
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PMID:A randomized double-blind study of gallium nitrate compared with etidronate for acute control of cancer-related hypercalcemia. 190 32

Salmon calcitonin has been used for the management of acute hypercalcemia for the past several years. Unlike other hypocalcemic agents, it is effective within 2 hours after first dosing. This pharmacologic agent shows peak effect at 24-48 hours and has a duration of action of 4-7 days in most cases. Its effectiveness may diminish thereafter despite continuous administration (the so-called "escape phenomenon"). Salmon calcitonin has been shown to be effective in the management of acute hypercalcemia due to a variety of causes, and, because of its low toxicity profile, it may be administered to patients with congestive heart failure or azotemia. Salmon calcitonin is also an analgesic agent in patients with pain associated with bone metastases and may be used in conjunction with other hypocalcemic agents such as mithramycin, the bisphosphonates, or gallium nitrate to prolong the clinical response to more than 1 week. Salmon calcitonin is therefore effective and safe in the management of acute hypercalcemia.
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PMID:Salmon calcitonin in the acute management of hypercalcemia. 213 63

Gallium nitrate has been used clinically to treat cancer-related hypercalcemia. It has been suggested that gallium may reduce calcium release from bone by inhibiting bone resorption, but the mechanism(s) involved remain to be elucidated. Therefore, we have examined the effect of gallium on bone resorption in vitro using osteoclasts isolated from neonatal rat long bones cultured on slices of cortical bone. Gallium nitrate (0.01-100 micrograms/ml) produced a concentration-dependent inhibition of bone resorption. Morphological studies showed that even (100 micrograms/ml) gallium nitrate induced no light microscopical change in osteoclast morphology and did not affect their survival on bone slices. Pretreatment of bone slices with gallium nitrate (100 micrograms/ml for 18 h), followed by extensive washing also inhibited subsequent osteoclastic bone resorption. These results suggest that gallium can be adsorbed onto the calcified surface of bone and inhibit osteoclastic bone resorption.
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PMID:Gallium inhibits bone resorption by a direct effect on osteoclasts. 227 60

Plasma calcium regulation in uranyl nitrate-treated dogs was studied. A discrete hypercalcemia was observed without significant changes in the level of plasma ionized calcium. Serum phosphate increased markedly following uranyl nitrate treatment. A sharp rise of iPTH was demonstrated. Uranyl nitrate-induced acute renal failure in dogs was found to be a useful model for studying the mechanisms regulating calcium and phosphate metabolism.
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PMID:Calcium and phosphate metabolism in uranyl nitrate-induced acute renal failure. 244 85


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