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 performed a retrospective analysis on all head and neck cancers with hypercalcemia seen between January 1988 and June 1993 at the Centre Oscar-Lambret, cancer center of northern France. Hypercalcemia, non albumin-corrected, higher than 2.60 mmol/l was observed in 173 of 3,394 consecutive patients (5%). Median age of patients with hypercalcemia was 53 years and 97% of these patients were males. All patients with hypercalcemia had advanced or recurrent and/or metastatic squamous cell carcinoma of head and neck (SCCHN); 31 of them were not pretreated. There was no significant difference in histology between patients with or without hypercalcemia, but hypercalcemia was most commonly associated with lesions of the oropharynx (p = 0.00001). The median of calcemia was of 2.83 mmol/l (2.61-4.70). Gastrointestinal and neurologic symptoms respectively occurred in 24% and in 14% of patients and bone metastases in 25% of patients. Median survival after the first determination of hypercalcemia was of 7 weeks (0-128) for the overall group of 173 patients and of 12 weeks (1-128) for those 31 patients with hypercalcemia at initial diagnosis. Prognosis associated factors were: efficacy of antitumour treatment, performance status and hypercalcemia superior or not to 3 mmol/l. We concluded that hypercalcemia in head and neck cancer is usually a late manifestation associated with advanced, recurrent and/or metastatic disease and carries a poor prognosis. The prolongation of survival can be obtained in some patients if an effective antitumour treatment is feasible.
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PMID:[Hypercalcemia and squamous cell carcinoma of the upper respiratory-digestive tracts. Incidence and prognosis]. 853 25

Acute hypercalcemia is commonly observed in surgical patients after calcium infusion while acute hypocalcemia is common during rapid citrated blood transfusion. Although high and low ionized calcium ([Ca2+]) within the clinical range produce an increase or decrease in cardiac performance and systemic vessel resistance, respectively, their effects on renal vessels have not been quantified. A possible renal vasoconstriction that might occur with high [Ca2+] is of clinical interest because it is a factor which may contribute to impaired renal circulation and decreased function. In this study we examined the renovascular responses to [Ca2+], which was varied within the clinical range under hemodynamically controlled conditions. We instituted high and low [Ca2+] in the per fusate, which consisted of Krebs-Henseleit buffer containing albumin, 60-65 g/liter. Stable high (n = 10) or low (n = 7) [Ca2+] (1.93 +/- 0.02 and 0.59 +/- 0.01 mM, respectively) was instituted for 10 min and preceded and followed by normal [Ca2+] of the same duration. In a separate protocol (n = 8) verapamil (10(-5) M) was added to the perfusate 10 min before high [Ca2+] was tested. We measured changes in renal flow at a constant perfusion pressure of 110 mm Hg and also characterized the renal vessels over a range of pressures by pressure vs flow plots. High [Ca2+] was associated with a small decrease in flow (from 28.8 +/- 2.4 to 26.9 +/- 2.6 ml/min/g, P < 0.02), indicating a small vasopressor effect. This effect was also shown by a leftward shift in the pressure vs flow plots. These changes were prevented by verapamil. GFR decreased (from 0.35 +/- 0.04 to 0.28 +/- 0.06 ml/min/ g, P < 0.01) without a significant change in sodium excretion or fractional sodium excretion. Low [Ca2+] was associated with increased renal flow (from 30.8 +/- 2.1 to 35.2 +/- 2.7 ml/min/g, P < 0.02), indicating a vasodilator effect. This effect was also shown by a rightward displacement of the pressure vs flow plots. GFR increased from 0.51 +/- 0.03 to 0.56 +/- 0.04 ml/min/ g, P < 0.01, as did sodium excretion (from 2.32 +/- 0.22 to 3.87 +/- 0.49 microEq/min, P < 0.01) and fractional sodium excretion (from 2.33 +/- 0.26 to 3.61 +/- 0.49%, P < 0.01). We conclude, first, that in the isolated perfused rat kidney, high [Ca2+] is a weak vasopressor while low [Ca2+] has vasodilator action. Second, high [Ca2+] effects are abolished by verapamil pretreatment. These findings illuminate mechanisms of high [Ca2+] effects on renovascular tone.
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PMID:Renovascular responses to high and low perfusate calcium steady-state experiments in the isolated perfused rat kidney with baseline vascular tone. 876 42

Intermittent high dose administration of calcitriol or alfacalcidol is effective in suppressing secondary hyperparathyroidism in chronic dialysis patients, however calcaemic action of these vitamin D derivatives is a major obstacle. 22-Oxacalcitriol (OCT) has been reported to have less calcaemic action than calcitriol, while preserving a comparable suppressive effect on parathyroid hormone (PTH) secretion. This preliminary study was conducted to examine the effects of OCT on secondary hyperparathyroidism in chronic dialysis patients. OCT was administrated intravenously immediately after every haemodialysis session three times a week for 12 weeks to three haemodialysis patients with secondary hyperparathyroidism. An initial dose of OCT of 5.5 micrograms/haemodialysis session was increased stepwise by 5.5 micrograms/haemodialysis up to 22 micrograms/haemodialysis according to the suppression of PTH and calcaemic action. OCT was discontinued for at least a week when serum calcium adjusted to albumin concentration measured just before haemodialysis exceeded 11.5 mg/dl. Marked reduction in plasma PTH, alkaline phosphatase and tartrate-resistant acid phosphatase was observed in all three patients. Although the dose of OCT was increased to 22 micrograms/haemodialysis in one patient, the final dose of OCT remained 5.5 micrograms/haemodialysis in the other two patients because of hypercalcaemia. It is concluded that OCT is highly effective in suppressing PTH in dialysis patients with secondary hyperparathyroidism. Hypercalcaemia may be a major factor which limits the use of OCT, though it may occur with higher doses of OCT than those of calcitriol usually given to suppress PTH hypersecretion.
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PMID:Effect of 22-oxacalcitriol on hyperparathyroidism of dialysis patients: results of a preliminary study. 884 Mar 26

A retrospective six-month study of serum calcium and albumin in patients treated at the Kuala Lumpur Hospital was carried out. There were 19,291 subjects, of which the prevalences of hypocalcemia (corrected serum calcium of < or = 2.1 mmol/l) and hypercalcemia (corrected serum calcium of > 2.7 mmol/l) were 18.0% (3460 subjects) and 2.4% (468 subjects) respectively. Persistent hypocalcemia (a minimum of first two consecutive corrected serum calcium of < or = 2.1 mmol/l) was found in 408/19,291 subjects 2.1%). Serum calcium values of < 2.00 mmol/l were found in 98.5% of this group. Persistent hypercalcemia (a minimum of first two consecutive corrected serum calcium of > 2.7 mmol/l) was found in 108/19,291 subjects (0.5%) and 52/108 subjects (48.1%) had serum calcium values of > or = 3.0 mmol/l. 2902/3460 subjects (83.8%) and 313/468 subjects (66.9%) the hypocalcemia and hypercalcemia groups respectively failed to be retested (singletons). In the hypocalcemia group, 1115/2902 (38.4%) showed corrected serum calcium values of < 2.00 mmol/l), whilst 100/313 subjects (31.9%) of the hypercalcemia group had corrected serum calcium values of > or = 3.00 mmol/l. There were no significant differences between the mean corrected serum calcium between 3 age groups of the test population, namely in childhood ( < or = 65 years).
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PMID:A retrospective study of serum calcium levels in a hospital population in Malaysia. 892 3

Calcitriol (1 alpha,25-dihydroxyvitamin D3), applied topically in an ointment base, has been shown to be effective in the treatment of chronic plaque psoriasis. This open study was designed to assess the safety and tolerability of 3 micrograms/g calcitriol ointment applied twice daily over treatment periods of up to 78 weeks. In the 253 evaluable patients with chronic plaque psoriasis no clinically relevant changes were observed in the baseline/end-point analyses of mean serum levels of total calcium, albumin-adjusted total calcium, phosphorus and creatinine, and plasma calcitriol levels. Mean values of 24-h urinary calcium, phosphorus, creatinine and hydroxyproline excretions, creatinine clearance and mean urinary calcium/creatinine ratio also did not show clinically relevant changes in the baseline/end-point analyses. The treatment was well tolerated, with no serious adverse events occurring during the course of the study. Eight patients withdrew from the study due to adverse events which, although not serious, were thought to be treatment-related: in seven patients skin irritation reactions and in one case a transient asymptomatic slight hypercalcaemia was observed. In addition, assessments of global severity, global improvement and Psoriasis Area and Severity Index scores confirmed the therapeutic efficacy of twice daily 3 micrograms/g calcitriol ointment demonstrated in an earlier controlled study. In conclusion, this study demonstrated that twice daily application of 3 micrograms/g calcitriol ointment is safe and well-tolerated in the treatment of chronic plaque psoriasis.
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PMID:A long-term multicentre assessment of the safety and tolerability of calcitriol ointment in the treatment of chronic plaque psoriasis. 894 30

There are many pathological causes and potential mechanisms for hypercalcemia. We measured intact parathyroid hormone (PTH) and parathyroid hormone related protein (PTHrP) in the hypercalcemic in-patients and attempted to evaluate the roles of PTH and PTHrP in hypercalcemia due to malignancy. We performed a prospective study of 178 patients with corrected serum calcium concentrations greater than 2.74 mmol/l in a hospital over a 3-year period. We measured calcium and albumin using a Hitachi 747 autoanalyzer, and we measured PTH and PTHrP by two-site immunoradiometric assays (IRMA). Hypercalcemia was attributed to malignancy alone in 93 patients (52.3%), primary hyperparathyroidism (HPT) alone in 28 patients (15.7%), uremia with hemodialysis in 23 patients (12.9%), unknown in 16 patients (9%), primary HPT coexisting with malignancy in 7 patients (3.9%) and other rare causes (6.2%). Plasma PTHrP levels were elevated in 71/93 (76.3%) patients with hypercalcemia due to malignancy, but the elevated PTHrP percentage differed for each kind of tumor. PTHrP levels were elevated in 100% of patients with squamous carcinomas (CA) in the lung, esophagus, skin, cholangiocarcinoma of liver, and breast CA. The positive bony metastatic rate was 44.1% (41/93). There was no correlation between high PTHrP and bony metastasis. There was a good correlation between the corrected serum calcium and PTHrP levels (r = 0.476, p < 0.001), but no correlation between survival time and serum calcium level or PTHrP level. There was no significant difference in life expectancy after cancer diagnosis between the high PTHrP group and normal PTHrP group, and there was no significant difference in life expectancy after the first occurrence of hypercalcemia between the two groups. Measurement of both PTH and PTHrP levels led to a change in the initial diagnosis in 7 patients. In routine practice, measurement of serum PTH alone is not enough. This study suggests that the appropriate combination of PTH and PTHrP assays results in a more accurate diagnosis of the hypercalcemic causes. In addition, especially high PTHrP levels should be screened for malignancy. However, the prognosis in cancer patients after hypercalcemia with high PTHrP group, as compared to those with the normal PTHrP group is not significantly different.
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PMID:Parathyroid hormone and parathyroid hormone related protein assays in the investigation of hypercalcemic patients in hospital in a Chinese population. 930 39

Ibandronate (ibandronic acid) is a third generation bisphosphonate which inhibits hone resorption in human and animal studies. It also inhibits bone formation only at high doses (10 microg/kg/day) in animal studies. In animal models, ibandronate was more potent than etidronate, clodronate, pamidronate and alendronate and equivalent in potency or more potent than risedronate in inhibiting induced hypercalcaemia and bone resorption. In clinical studies, single-dose ibandronate (0.2 to 6 mg intravenously) significantly reduced albumin-corrected serum calcium levels and urinary markers of bone resorption in patients with hypercalcaemia of malignancy, and in those with bone metastases. Serum calcium levels were normalised in 50 and 67% of ibandronate 2 mg recipients and in about 76% of 4 mg recipients. In postmenopausal women with osteoporosis or osteopenia. ibandronate (0.5 to 5 mg/day orally or 0.5 to 2 mg every 3 months intravenously) dose-dependently increased bone mineral density, with parallel reductions in the biochemical markers of bone turnover. In preliminary studies in patients with Paget's disease a single intravenous ibandronate dose (2mg) decreased serum alkaline phosphatase levels and urinary markers of bone turnover. Adverse events associated with the use of ibandronate in the management of hypercalcaemia of malignancy include increased body temperature, hypocalcaemia and hypophosphataemia. Less commonly, flu-like symptoms and gastrointestinal intolerance may occur.
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PMID:Ibandronate. 995 55

Since dietary restrictions and phosphorus removal by haemodialysis (HD) are not sufficient to control serum phosphate (s-phosphate) levels in dialysis patients the use of oral phosphate binders is mandatory. Calcium ketoglutarate (CaKE) is an analogue of glutamic acid exerting phosphate binding properties. Therefore we compared this substance to calcium acetate (CaAC) in a 24-weeks open cross-over trial in 28 maintenance HD patients. Medications and HD prescriptions were kept unchanged during the trial. Following 2 weeks of withdrawal of phosphate binders, patients were randomly assigned to one of the calcium salts for 12 weeks; after a second withdrawal of 2 weeks, all patients were shifted to the other treatment for another 12 weeks. All patients received equimolar doses of CaKE and CaAC with respect to the amount of prescribed elemental calcium. Treatment with CaAC and CaKE significantly reduced s-phosphate levels after 4 weeks (CaAC 1.95+/-0.6 vs. 2.4+/-0.53 mmol/l, P = 0.004; CaKE 1.95+/-0.4 vs. 2.47+/-0.63 mmol/l, P = 0.0001) reaching a virtually stable plateau over the remaining observation time without significant differences between the groups. The incidence of hypercalcaemia defined as a serum calcium level > or =2.8 mmol/l was significantly higher in CaAC than in CaKE treated patients (n = 8 vs. n = 1, P = 0.03). There were no significant differences in serum intact parathyroid hormone (PTH) bicarbonate, albumin or calcitriol levels between the groups after 12 weeks treatment. We conclude that CaKE is as effective as CaAC for treatment of hyperphosphataemia in chronic HD patients and may be particularly helpful in patients who are prone to develop hypercalcaemia.
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PMID:Calcium ketoglutarate versus calcium acetate for treatment of hyperphosphataemia in patients on maintenance haemodialysis: a cross-over study. 1038 11

Zoledronate is a new heterocyclic imidazole bisphosphonate that is the most potent bisphosphonate administered in humans because it is 100-850 times more potent than pamidronate, according to in vitro or animal models of bone resorption. We conducted an open-label, dose-finding, single-dose phase I study in tumor-induced hypercalcemia (TIH), which has been similarly used as a model to determine the active doses of other bisphosphonates. The primary objective was to determine, with a dose escalation schedule, two nontoxic dose levels of zoledronate able to induce normocalcemia in at least 80% of patients with TIH after rehydration (corrected Ca for albumin levels >/=2.75 mmol/l). Based on estimates of potency, the starting dose was 0.002 mg/kg, and further tested doses were 0. 005, 0.01, 0.02, and 0.04 mg/kg. To obtain a more precise estimate of the response rate, we treated 10 more patients at the highest of the two effective dose levels. The median infusion time of zoledronate was 30 minutes. Thirty out of the 33 treated patients were evaluable for efficacy. Thirty percent of the patients had breast cancer and 54% had metastatic bone involvement. For all groups combined, mean Ca levels at baseline was 3.0 mmol/l. The two effective dose levels were 0.02 mg/kg and 0.04 mg/kg. Five out of five patients became normocalcemic after 0.02 mg of zoledronate/kg and 14 out of 15 after 0.04 mg of zoledronate/kg. The success rate of the latter dose was thus 93% (95% confidence interval [CI] 68-100%). At this dose, the first day of normocalcemia was day 2 or 3 for all but one patient. The duration of normocalcemia for the two effective doses could be assessed in nine patients; seven patients remained normocalcemic throughout the trial (32-39 days). The fall in serum Ca was accompanied by a marked fall in fasting urinary Ca excretion. Zoledronate was well tolerated: 7 out of 33 patients developed transient hypophosphatemia, and 3 developed transient hypocalcemia. The only clinically detectable side effect was an increase in body temperature occurring in 10 (30%) patients. In summary, very low doses of zoledronate (0.02 mg/kg and 0.04 mg/kg, i. e., 1.2 mg and 2.4 mg for a 60-kg individual, respectively) administered by a short-time infusion effectively treated patients with TIH. The fall in serum Ca was rapid, and normocalcemia was often maintained for several weeks. Zoledronate was well tolerated. Future trials will determine whether prolonged treatment with this potent compound can have greater effects on the skeletal morbidity rate in patients with tumor bone disease than can be achieved with currently available bisphosphonates.
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PMID:A dose-finding study of zoledronate in hypercalcemic cancer patients. 1046 84

The pathogenesis of hypercalcemia of malignancy comprises increased net bone resorption and enhanced renal tubular reabsorption of calcium (Ca). To evaluate the prevalence of an increased renal tubular reabsorption of Ca index [tubular reabsorption of calcium index (TRCaI)] in cancer patients with hypercalcemia and of elevated circulating levels of PTH-related protein (PTHrP), which is recognized as a major mediator of this syndrome, we investigated 315 well rehydrated patients, aged 58.1 +/- 0.7 yr (mean +/- SEM), with hypercalcemia [albumin-corrected plasma Ca (pCa), >2.7 mmol/L] secondary to histologically proven malignancy. Changes in pCa and, therefore, various Ca filtered loads were obtained by different degrees of bone resorption inhibition achieved with a single infusion of the bisphosphonate ibandronate, given at various doses on a randomized, double blind basis. PTHrP was determined at baseline in 147 of the patients and 7 days after bisphosphonate therapy in 73. Before ibandronate therapy, pCa was 3.36 +/- 0.02 mmol/L, mean TRCaI was increased at 3.09 +/- 0.03 mmol/L glomerular filtration rate (GFR; normal, 2.40-2.90), and 65% of patients had TRCaI above 2.90 mmol/L GFR. Mean serum PTHrP levels were 4.9 +/- 0.5 pmol/L (normal, <2.5) and values above the normal range were found in 53% of the patients (76% in lung and upper respiratory tract malignancies). By 7 days after the infusion of ibandronate, a decrease in pCa of 0.69 +/- 0.03 mmol/L (20.0 +/- 0.7%; P < 0.001) and in bone resorption [mean change in fasting urinary Ca, 0.09 +/- 0.04 mmol/L GFR (47.6 +/- 8.6%; P < 0.001) and 14.4 +/- 1.7 nmol/mmol (27.6 +/- 10.6%; P < 0.01) in deoxypyridinoline] was observed. TRCaI was slightly lowered by 0.30 +/- 0.09 mmol/L GFR. Mean changes in PTHrP, 1,25-dihydroxyvitamin D3, and PTH were +0.7 +/- 0.4 (P = NS), +27.6 +/- 3.0 (P < 0.001), and +2.9 +/- 0.8 (P < 0.005) pmol/L, respectively. After ibandronate treatment, the relative risk of relapsing hypercalcemia was particularly increased (3.43-fold) in lung and upper respiratory tract malignancies. These results obtained in a large cohort of patients indicate a significant prevalence of an increased renal tubular reabsorption of calcium index in hypercalcemia of malignancy and a substantial proportion of patients with detectable PTHrP.
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PMID:Serum parathyroid hormone-related protein levels and response to bisphosphonate treatment in hypercalcemia of malignancy. 1052 93


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