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)

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

Breast and prostate carcinomas are the tumors most commonly associated with skeletal metastases, and the skeleton is the most common site of metastatic disease and of first distant relapse in breast cancer. Bone metastases are the source of considerable morbidity, including pain and functional disability, fractures, hypercalcemia, and epidural compression. The classical radionuclide bone scan remains the most effective tool for the screening of metastatic bone disease, but X-rays are more specific and remain the essential tool for the diagnosis and characterization of bone metastases. Computed tomography is much more useful to diagnose early metastatic involvement of bone, particularly of the spine. Patients with exclusive skeletal metastatic involvement are still frequently excluded from classical therapeutic trials because of the difficulties in the assessment of response. Recalcification of osteolytic lesions is indeed required when defining an objective response, but this criterion is insensitive and not quantitative. Moreover, the development of new osteoblastic lesions is often of difficult interpretation. A concomitant bone scan will help, but the absence of quantification of the changes and the "flare" phenomenon limit the usefulness of the technique. Pain and quality of life constitute simple, but frequently neglected, parameters of response to therapy. The clinical utility of tumor markers and of biochemical markers of bone turnover should also be more fully investigated. Neoplastic osteolysis is essentially mediated by the osteoclasts, which seem to be activated, maybe indirectly through the osteoblasts, by some tumor products. Various substances of tumoral origin have been proposed as mediators for this osteoclast activation, such as transforming growth factors, prostaglandins, and, more recently, products of the immune cells or parathyroid hormone-related peptide.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Metastatic bone disease: clinical and therapeutic aspects. 158 Nov 21

The presence of parathyroid hormone related protein (PTHRP) in human breast cancers has been assessed by immunohistochemistry using a polyclonal antiserum specific for the mid-region sequence 37-67 in an immunoperoxidase technique. The primary tumours from 155 normocalcaemic, consecutive women with early breast cancer who had been followed up for a minimum of 5 years were assessed. Dewaxed paraffin sections of formalin fixed tissue was used throughout. Positive PTHRP staining was detected in 56% of the cancers and was unrelated to standard prognostic factors, recurrence or survival. However, PTHRP positivity was related to the development of bone metastases (P less than or equal to 0.03) and hypercalcaemic episodes. PTHRP is implicated as the humoral factor responsible for hypercalcaemia associated with breast cancer and tumour positivity may be a useful predictor of which women will develop bone metastases.
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PMID:Parathyroid hormone related protein and skeletal morbidity in breast cancer. 159 Oct 95

Pamidronate [aminohydroxypropylidene diphosphonate disodium (APD), disodium pamidronate] is an orally and intravenously active amino-substituted bisphosphonate which produces potent and specific inhibition of bone resorption at doses devoid of any significant detrimental effect on bone growth and mineralisation. Clinical trials indicate that pamidronate is effective in a variety of conditions characterised by pathologically enhanced bone turnover, including Paget's disease, hypercalcaemia of malignancy, osteolytic bone metastasis, steroid-induced osteoporosis and idiopathic osteoporosis. Pamidronate is highly effective in restoring normocalcaemia in patients with hypercalcaemia of malignancy associated with bone metastases but, in common with other bisphosphonates, is marginally less effective against humoral hypercalcaemia of malignancy. Comparative studies in this area have suggested that, at therapeutic doses, pamidronate has a more pronounced calcium-lowering action than etidronate (etidronic acid) and clodronate (clodronic acid) and provides a longer period of normocalcaemic remission. In Paget's disease arrest and, in some patients, reversal of the progression of osteolytic lesions by pamidronate is associated with a sustained reduction in bone pain, improved mobility and a possible reduced risk of bone fracture. In patients with osteolytic bone metastasis pamidronate reduces skeletal morbidity and slows the progression of metastatic bone destruction. Long term use of low-dose pamidronate in conjunction with conventional antiosteoporotic therapy may halt bone loss in steroid-induced and idiopathic osteoporosis. Pamidronate appears to represent a valuable addition to the drugs currently available for the treatment of symptomatic Paget's disease and cancer-associated hypercalcaemia, and shows promise in the treatment of osteolytic bone metastasis and osteoporosis.
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PMID:Pamidronate. A review of its pharmacological properties and therapeutic efficacy in resorptive bone disease. 170 54

The reported studies of clodronate in the management of osteolytic bone metastases suggest a significant palliative role for this drug. In this paper we report on analysis of the hospital costs associated with the management of osteolytic metastatic disease, and an estimate of the potential cost/benefit impact of clodronate therapy. Two separate patient populations were assessed retrospectively. The first, a sample of 120 patients with symptomatic bone metastases who had died from metastatic breast cancer over the period 1980-1990, was used to define the natural history of the disease. A second non-concurrent patient group of 337 patients was evaluated to determine the mean cost of all hospital admissions for patients with bone metastases from breast carcinoma. The length of stay and costs for hospital admissions related to the bone metastases were also assessed, in addition to the cost of out-patient radiation therapy. Our cost/benefit value analysis suggests that there are significant savings to be gained from the use of clodronate if a 20% or greater reduction occurs in the incidence of fractures, hypercalcaemia, and hospital-based treatment for pain control (via radiotherapy). We also speculate that the quality of life of patients with osteolytic bone metastases may be improved with this agent.
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PMID:An evaluation of the potential cost reductions resulting from the use of clodronate in the treatment of metastatic carcinoma of the breast to bone. 172 13

Osteolytic bone metastases secondary to breast cancer are extremely common, occurring in more than 50% of breast cancer patients. The resulting increased bone resorption leads to significant symptomatic morbidity caused by bone pain, hypercalcaemia and pathological fracture. Clodronate, an anti-osteolytic agent, inhibits osteoclastic bone resorption and has considerable therapeutic value. Recent studies have shown that clodronate is effective in the treatment of malignancy hypercalcaemia, relief of bone pain and decreases the risk of pathological fracture. The use of clodronate in the future, other than as a palliative therapy, may focus upon the prevention of osteolytic bone metastases at the time of primary diagnosis or later in the disease progression in those patients at risk, for example, those with non-osseous relapse. Since patients with bone metastases secondary to breast cancer often have an increased duration of survival, any agent that would decrease the symptomatic morbidity would have a significant impact upon quality of life, even more so if the actual development of osteolytic bone metastases was delayed or prevented.
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PMID:Clodronate: the potential for the future. 172 14

Calcitonin has been used clinically to treat hypercalcemia, Vitamin D intoxication, osteolytic bone metastases and increased skeletal remodeling in Paget's disease. In general calcitonin is given every 6 to 12 hrs intramuscularly or subcutaneously. It has been found in this study that the same results can be achieved by giving calcitonin through eyes as ophthalmic solutions. When 25 microliters of 0.05% calcitonin was given as eyedrops to New Zealand white rabbits, it did not reach the concentration achieved by i.v. administration at the same dose level. The systemic absorption of calcitonin did not reach the level achieved by i.v. administration even though the eyedrop concentrations were increased 2-fold (0.1%) to 10-fold (0.5%). When absorption enhancers such as BL-9 and Brij-78 were added to calcitonin eyedrops, however, the systemic absorption of calcitonin was enhanced markedly. BL-9 (0.5%) increased calcitonin (0.5%) absorption 16-20 fold and raised blood concentration of calcitonin above levels achieved by i.v. injection (25 microliters, 0.05%) with 0.5% calcitonin eyedrops instillation. Effects of Brij-78 (0.5%) were even more impressive. It increases calcitonin absorption 22-24 fold and raised the blood concentration of calcitonin above the levels achieved by i.v. injection (25 microliters 0.05%) with 0.15% and 0.5% calcitonin eyedrops instillation. These results indicate that the therapeutic level of calcitonin can be reached through the ocular route.
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PMID:Systemic administration of calcitonin through ocular route. 173 6

We evaluated the incidence of hypo- versus hypercalcemia and hypo- versus hyperphosphatemia in a survey of 158 patients with malignancy; 55/158 had bone metastases. When serum calcium levels were corrected for albuminemia, the incidence of hypo- and hypercalcemia was respectively 10.8% and 10.1%. Hypophosphatemia was found in 29.7% patients, hyperphosphatemia in 2.5%. The incidence was slightly different in presence of bone metastases. Hypocalcemia and hypophosphatemia prevailed in osteoblastic metastases and hypercalcemia in osteolytic metastases. The incidence of hypocalcemia and hypophosphatemia in malignancy was therefore surprisingly high, even apart from the presence of bone metastases. Both hypo- and hypercalcemia were associated with elevated serum alkaline phosphatase levels. Moreover, a calcium-phosphorus product reduction was observed in osteoblastic metastases, suggesting a condition of secondary hyperparathyroidism.
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PMID:A hospital survey of hypocalcemia and hypophosphatemia in malignancy. 174 50

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

A region-specific radioimmunoassay has been employed to measure levels of immunoreactive parathyroid hormone-related protein(50-69) (iPTHrP(50-69)) in patients with tumour-induced hypercalcaemia (TIH). This assay is based on an antiserum raised against synthetic human PTHrP(50-69). The assay showed no cross-reactivity with human or bovine parathyroid hormone(1-84). The effect of a single dose (60 mg) of pamidronate was studied in 25 consecutive patients with TIH. All were rehydrated prior to treatment. All but 2 patients (8%) became normocalcaemic after treatment; both of these had very high levels of iPTHrP(50-69). Time to achieve normocalcaemia, as an index of relative resistance to pamidronate, correlated positively with pretreatment level of iPTHrP(50-69). Absence of radiological evidence of bone metastases also predicted relative resistance to pamidronate. In this study, iPTHrP(50-69)-induced osteoclastic bone resorption was a more important mechanism in the causation of TIH than PTHrP-induced renal reabsorption of calcium as assessed by the renal thresholds for calcium and phosphate.
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PMID:Parathyroid hormone-related protein(50-69) and response to pamidronate therapy for tumour-induced hypercalcaemia. 178 72


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