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)

Seventeen patients with malignant hypercalcemia were treated with a combination of a single dose of 3-amino 1-hydroxypropylidene-1-bisphosphonate (APD [also known as AHPrBP or palmidronate disodium]) and salmon calcitonin given as suppositories for 3 days. To assess whether such a combined short treatment has a significant benefit leading to earlier normalization of the plasma calcium level than does APD alone, 17 additional patients matched for the type of tumor, initial plasma calcium level, urinary hydroxyproline level, and the dose of APD served as controls. All patients receiving the combination of calcitonin and APD achieved normalization of the plasma calcium level within 9 days, with a decrease from 3.22 +/- 0.90 mmol/L (mean +/- SEM) to 2.29 +/- 0.03 mmol/L. In the group receiving APD alone, the plasma calcium level normalized in only 14 of 17 patients by day 9. In the group receiving calcitonin and APD, the drop in the plasma calcium level occurred more rapidly, and the plasma calcium values were lower from days 2 to 4. This advantage was explained by the calciuric effect of calcitonin, as reflected by a significant decrease in the notional setting of renal reabsorption of calcium, reaching 2.16 +/- 0.06 mmol/L compared with 2.34 +/- 0.06 mmol/L in the group receiving APD alone. There were no side effects of both treatments, in particular neither flushing nor nausea induced by the suppositories of calcitonin. Clinical Improvement occurred after 2 days in the group receiving the combined treatment. In conclusion, the combined treatment is rapidly effective and safe in the treatment of patients with hypercalcemia, particularly when the notional setting of renal tubular reabsorption of calcium is increased and a rapid correction of the plasma calcium level is needed.
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PMID:Fast and effective treatment of malignant hypercalcemia. Combination of suppositories of calcitonin and a single infusion of 3-amino 1-hydroxypropylidene-1-bisphosphonate. 222 97

Hypercalcemia is one of the most critical complications in patients with malignancy. We have used salmon calcitonin for treatment of hypercalcemia in these patients. The subjects were 49 hypercalcemic patients with various malignancies. Synthetic salmon calcitonin (SCT) was provided by Teikoku Hormone Mfg. Co. Ltd., Japan and 40 MRC units was administered twice daily i.m. or i.v. In 21 of 33 cases treated i.m. and in 8 of 16 cases treated i.v., a serum Ca decrease of more than 2 mg/dl was observed. The hypercalcemia was managed in 59% of patients within 6 days after initiation of the treatment and effective duration was 14 days. On the other hand, ineffective cases treated with a combination of SCT and glucocorticoid or SCT and mithramycin were managed in 57% and 86%. The 50% survival time was 69 days in the effective cases and 23 days in the uncontrolled cases (P less than 0.01). The main causes of death in the ineffective cases were renal insufficiency. On the other hand, in the effective cases, improvements of renal function were observed. The side effects were slight, and nausea and flushing were observed in 24% of cases. These data indicate that SCT is effective for lowering the serum Ca level in hypercalcemic patients with malignancies.
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PMID:[Synthetic salmon calcitonin as an antihypercalcemic agent for hypercalcemia in malignancy]. 374 Aug 62

Elcatonin, used for treatment of hypercalcaemia, Paget's disease and osteoporosis, causes flushing of the face and hands. To determine whether this was because of increased levels of vasoactive intestinal peptide, which is known to induce vasodilation, the effect of elcatonin on the plasma levels of vasoactive intestinal peptide was studied in five healthy volunteers. After a single intramuscular administration of elcatonin (20 int units), peak plasma elcatonin levels (approx. 30 pg mL-1) were achieved 30 min after injection. Plasma vasoactive intestinal peptide concentrations rose similarly with peak levels of about 17 pg mL-1 after 30 min. Side-effects such as cutaneous flushing (most obvious in the face and hands) occurred to an extent dependent on the amount of elcatonin administered, and declined over 45 min in parallel with the fate of plasma vasoactive intestinal peptide. The side-effects of elcatonin, especially cutaneous flushing, seem to be closely connected with vasoactive intestinal peptide.
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PMID:Elcatonin raises levels of vasoactive intestinal peptide in human plasma. 883 4

9-cis-Retinoic acid (9-cis-RA) and all-trans-RA (ATRA) are naturally occurring hormones. The nuclear receptors that mediate the effects of retinoids are the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). ATRA binds RAR with high affinity but does not bind to RXR, whereas 9-cis-RA, an isomer of ATRA, is a ligand that binds and transactivates both RARs and RXRs. The goals of this study were to determine the safety, tolerability, pharmacokinetics, and metabolic profile of 9-cis-RA in advanced cancer patients. Forty-one patients received oral 9-cis-RA (ALRT1057; Panretin capsules) at doses ranging from 5-140 mg/m2/day. Twenty-six patients were treated once daily with up to 140 mg/m2; a subsequent cohort of 15 patients were treated twice daily (b.i.d.) at 100-140 mg/m2/day (50, 60, and 70 mg/m2 b.i.d.) to evaluate a b.i.d. dosing regimen. Headache was the most frequent adverse event and was dose limiting in 3 of 41 patients. Skin toxicity was the next most common toxicity and was seen in 11 of 41 patients; it was typically mild and limited to skin dryness and erythema. Other toxicities included conjunctivitis, flushing, diarrhea, transaminitis, hypercalcemia, and asymptomatic hypertryglyceridemia. Toxicities were typically dose related, occurred primarily above 83 mg/m2/day, and were not ameliorated by b.i.d. dosing. No tumor responses were observed. The mean day 1 area under the plasma concentration-time curve and peak plasma concentration values were dose-proportional over all dose levels, whereas day 15 area under the plasma concentration-time curve and peak plasma concentration values were nonlinear above 83 mg/m2/day, suggesting that 9-cis-RA induced its own metabolism at doses equal to and above 140 mg/m2/day. 9-cis-RA is a retinoid receptor pan agonist with a more favorable pharmacokinetic and toxicity profile than that observed with previously studied retinoids and merits further investigation.
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PMID:Phase I study of 9-cis-retinoic acid (ALRT1057 capsules) in adults with advanced cancer. 962 60

The retinoid response is mediated by families of nuclear receptors, the retinoic acid receptors (RARs), and the retinoid X receptors. All-trans retinoic acid (RA) binds only RARs and induces its own metabolism. In contrast, 9-cis RA is a newly identified agonist for both RARs and retinoid X receptors. We undertook a dose-ranging study to examine the safety, clinical tolerance, and pharmacokinetics of 9-cis RA in patients with advanced cancer. Thirty-four patients received once daily p.o. doses of 9-cis RA (administered as LGD1057) ranging from 5 to 230 mg/m2 for 4 weeks. Pharmacokinetic studies were performed on 28 patients at seven dose levels. 9-cis RA was generally well tolerated. Headache was the most common dose-limiting adverse effect. Other prominent reactions included facial flushing, myalgia, dyspnea, hypertriglyceridemia, and hypercalcemia. Relative to other retinoids, mucocutaneous reactions were mild. No major antitumor responses were observed. Pharmacokinetic analysis revealed that the day 1 area under the plasma concentration x time curves (AUCs) were proportional to the dose. Up through doses of 140 mg/m2, the day 1 AUCs were similar to those on days 15 and 29. At higher doses, however, AUCs tended to decline with repeat dosing. 9-cis RA is a novel compound that exploits a newly identified pathway of retinoid receptor biology that may be relevant to tumor cell proliferation and differentiation. We recommend a dose of 140 mg/m2 for single-agent trials utilizing a once-daily schedule of administration.
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PMID:Initial clinical trial of the retinoid receptor pan agonist 9-cis retinoic acid. 981 92

Supportive care of patients with functional neuroendocrine tumors (NETs) has evolved to include the use of multiple targeted agents to control paraneoplastic states and newer surgical and interventional radiologic techniques to reduce tumor bulk. Challenges encountered by the clinician are the recognition of specific symptom complexes, selecting the relevant laboratory tests and radiologic/scintigraphic scans, and the timing of intervention(s). Individual variables such as the severity of symptoms in the context of primary and metastatic disease sites, tumor bulk, comorbidities, and previous treatment are factors determining the prioritization of specific treatment regimens for patients with functional NETs. Symptoms such as flushing, secretory diarrhea, hypercalcemia, hyper /hypoglycemia, hypercortisolism, and peptic ulcers should improve with decreasing the elevated amino acid and/or peptide levels produced by NETs. These paraneoplastic symptoms may be accompanied by complaints related to tumor burden such as fatigue, pain, early satiety, anorexia, weight loss, night sweats, and/or symptoms secondary to adverse drug effects such as mucositis, dysgeusia, diarrhea, rash, hypertension, and myelosuppression. Developing a comprehensive continuum of care plan early in disease management assists in controlling the presenting signs and symptoms, and in minimizing disease- and/or treatment-related side effects. This guide serves as a framework to manage the signs and symptoms of metastatic functional neuroendocrine tumors.
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PMID:Practical guide to supportive care of patients with functional neuroendocrine tumors. 2339 Nov 12

History A 61-year-old woman with well-controlled diabetes presented with a 10-year history of hypertension, stifling sensation, and flushing. Her body mass index was 19.1 kg/m(2) (normal range, 18.5-25.0 kg/m(2)). She was being followed up for mild hypercalcemia (calcium level, 10.8 mg/dL [2.7 mmol/L]) (normal range, 8.5-10.5 mg/dL [2.12-2.62 mmol/L]) by the endocrinologist (S.J.M.), who decided to perform a technetium 99m sestamibi ((99m)Tc MIBI) parathyroid scan. The test showed an abnormal tracer deposit in the region of the clavicle and sternum; thus, unenhanced thoracic computed tomography (CT) was performed. No mass was seen in the region of abnormality. In light of these findings, the patient underwent contrast material-enhanced (120 mL of iopromide, Ultravist 300; Schering, Berlin, Germany) thoracic abdominopelvic CT. There was no history of underlying malignancy, and the complete blood counts were normal. The axial and appendicular skeleton showed no sign of lesions.
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PMID:Case 214: Adrenal pheochromocytoma with perirenal brown fat stimulation. 2562 45