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)

The objective of the study was to evaluate the phosphate-binding efficacy, side effects, and cost of therapy of calcium ketoglutarate granulate as compared with calcium carbonate tablets in patients on chronic hemodialysis. The study design used was a randomized, crossover open trial, and the main outcome measurements were plasma ionized calcium levels, plasma phosphate levels, plasma intact parathyroid hormone (PTH) levels, requirements for supplemental aluminum-aminoacetate therapy, patient tolerance, and cost of therapy. Nineteen patients on chronic hemodialysis were treated with a dialysate calcium concentration of 1.25 mmol/L and a fixed alfacalcidol dose for at least 2 months. All had previously tolerated therapy with calcium carbonate. Of the 19 patients included, 10 completed both treatment arms. After 12 weeks of therapy, the mean (+/-SEM) plasma ionized calcium level was significantly lower in the ketoglutarate arm compared with the calcium carbonate arm (4.8+/-0.1 mg/dL v 5.2+/-0.1 mg/dL; P = 0.004), whereas the mean plasma phosphate (4.5+/-0.3 mg/dL v 5.1+/-0.1 mg/dL) and PTH levels (266+/-125 pg/mL v 301+/-148 pg/mL) did not differ significantly between the two treatment arms. Supplemental aluminum-aminoacetate was not required during calcium ketoglutarate treatment, while two patients needed this supplement when treated with calcium carbonate. Five of 17 (29%) patients were withdrawn from calcium ketoglutarate therapy within 1 to 2 weeks due to intolerance (anorexia, vomiting, diarrhea, general uneasiness), whereas the remaining 12 patients did not experience any side effects at all. The five patients with calcium ketoglutarate intolerance all had pre-existing gastrointestinal symptoms; four of them had received treatment with cimetidine or omeprazol before inclusion into the study. Calculations based on median doses after 12 weeks showed that the cost of the therapy in Denmark was 10 times higher for calcium ketoglutarate compared with calcium carbonate (US$6.00/d v US$0.65/d). Calcium ketoglutarate may be an effective and safe alternative to treatment with aluminum-containing phosphate binders in patients on hemodialysis who are intolerant of calcium carbonate or acetate because of hypercalcemia. However, care must be exercised when dealing with patients with pre-existing gastrointestinal discomfort. Due to the high cost of the therapy, calcium ketoglutarate should be used only for selected patients.
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PMID:Randomized crossover study comparing the phosphate-binding efficacy of calcium ketoglutarate versus calcium carbonate in patients on chronic hemodialysis. 946 96

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

Retinoids have been shown to be potent inhibitors of epithelial carcinogenesis. Recent evidence has demonstrated that retinoid actions are mediated through nuclear receptors, which are proteins encoded by the retinoic acid receptor and retinoid X receptor gene families. These receptors are activated by binding to specific retinoids; of the known naturally occurring retinoids, 9-cis retinoic acid is unique in its ability to bind to both receptor families. Because of its unique receptor-binding characteristics, 9-cis retinoic acid may have biological activity not possible with other retinoids. For this reason, we conducted a Phase I trial of 9-cis retinoic acid in adult patients with solid tumors. Twenty-two patients were treated twice daily with p.o. 9-cis retinoic acid at doses ranging from 20 mg/m2/day to 150 mg/m2/day. The patients had non-small cell lung cancer (n = 8), breast cancer (n = 5), colorectal cancer (n = 3), head and neck cancer (n = 2), nonmelanoma skin cancer (n = 2), or ovarian cancer (n = 2). The dose-limiting (WHO grade III) toxic effects, which occurred at the 150-mg/m2/day dose level, were headaches and diarrhea. Less severe (grades I and II) toxic effects included cheilitis, dry skin, conjunctivitis, fatigue, hypertriglyceridemia, alkaline phosphatase elevation, myalgia/arthralgia, and hypercalcemia. Of the 15 patients evaluable for tumor response, no objective responses were observed. Pharmacokinetic analysis revealed a reduction in peak 9-cis retinoic acid plasma levels with chronic administration. Based on this study, the recommended Phase II dose of 9-cis retinoic acid in adult patients with solid tumors is 100 mg/m2/day administered in a divided dose twice daily.
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PMID:Phase I trial of 9-cis retinoic acid in adults with solid tumors. 981 71

Polydextrose (CAS no. 68424-04-4) is a water-soluble polymer of glucose that provides to foods the bulk and texture of sucrose. There are two main forms of polydextrose, an acidic form (PD-A) and a neutralized potassium salt (PD-N). Polydextrose is resistant to mammalian metabolic and microbial degeneration, rendering it both low in caloric value and non-cariogenic. Little polydextrose is absorbed intact although some is metabolized by caecal/colonic bacteria. At high enough levels of ingestion, this bacterial metabolism results in flatus, bloating, loose stools and ultimately a frank diarrhoea. Microbial metabolism also produces some volatile fatty acids that are absorbed by the animal and have calorigenic value. The species and dose threshold for persistent loose stools/watery diarrhoea determines the degree of electrolyte loss by the animal. In the dog, an obligate carnivore, sodium-sparing activity by the kidney and concomitant and obligatory calcium reuptake result in a well-defined aetiology of hypercalcaemia and subsequent nephrocalcinosis, particularly for PD-N. Of the species tested, the dog was the most sensitive to this carbohydrate with a no-effect level of 2000 mg/kg body weight/day. Omnivores, including the rat, mouse and monkey, have a no-effect level ranging from 2500 to 10,000 mg/kg body weight/day. No toxicity has been demonstrated in man, although the dose for laxation (to be distinguished from diarrhoea) is approximately 90 g/day (v. sorbitol at 70 g/day). Polydextrose did not show any reproductive toxicity, teratology, carcinogenesis, mutagenicity or genotoxicity. Polydextrose has been approved for food additive use (21 CFR 172.841) in the US, and an "ADI not specified" by the Joint WHO/FAO Expert Committee on Food Additives (JECFA, 1987). It has been approved in over 50 countries around the world and has been used extensively in the diet for over15 years. Specification monographs are published in the Food Chemicals Codex (FCC) (NAS, 1996) and the FAO Compendium (JECFA, 1995). This review provides an overview of the studies and salient data, not previously reported in the scientific literature, which had been submitted to regulatory agencies in support of these approvals.
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PMID:A review of the studies of the safety of polydextrose in food. 1022 45

LGD1069 [Targretin; 4-[1-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphtalenyl) propenyl] benzoic acid] is a novel synthetic retinoid X receptor-selective retinoid that has been recently identified. The goals of this study were to determine the safety, toxicity, pharmacokinetics (PKs), and metabolic profile of LGD1069 in advanced cancer patients. Sixty patients received oral LGD1069 at doses ranging from 5-1000 mg/m2/day with PK sampling performed on days 1 and 15. No dose-limiting toxicities (DLTs) were observed up to the 500 mg/m2/day dose level. DLT observed at and above 650 mg/m2/day included skin desquamation, hyperbilirubinemia, transaminase elevation, leukopenia, and diarrhea. Asymptomatic, dose-related alterations in lipid and thyroid metabolism were also observed. DLTs frequently observed with retinoic acid receptor-selective retinoids and pan agonists, including headache, mucocutaneous toxicity, and hypercalcemia, were not dose-limiting with LGD1069. Day 1 LGD1069 Cmax and area under the curve values increased dose-proportionately up to 800 mg/m2/day. Repeat-dose (day 15) area under the curve values varied between 25 and 105% of day 1 values. Although no objective tumor responses were observed, tumor progression may have been substantially arrested or delayed in non-small cell lung cancer (5 of 16) and in head and neck cancer (1 of 5), as well as other tumor types. At the higher dose levels, the molar concentration of LGD1069 was up to 10-fold higher than observed with other retinoids, yet toxicity was minimal. LGD1069 is an retinoid X receptor-selective retinoid agonist with a more favorable PK and toxicity profile than previously studied retinoids and merits further investigation as a chemopreventive and anticancer agent. On the basis of this Phase I trial, the recommended Phase II dose is 500 mg/m2/day.
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PMID:A Phase I study of LGD1069 in adults with advanced cancer. 1043 65

We report a case of a 35-year-old male, with a history of diarrhea, renal lithiasis with frequent expulsions of calculus and hypercalcemia during the last 2 years. The patient was studied and diagnosed with a multiple endocrine neoplasia type I (MEN I), familiar (mother with MEN I). A scintigraphic study with 99mTc-MIBI was performed in order to localize hyperfunctioning parathyroid glands because of biochemical diagnosis of primary hyperparathyroidism. Double phase 99mTc-MIBI scan detected one hyperfunctioning parathyroid gland and a large anterior mediastinal mass. Subsequent, plain radiograph and CT of the chest showed a soft-tissue mass in that localization. Punch biopsy of the lesion guided by CT revealed malignant cells of neuroendocrine tumor. The tumor was removed and histologically confirmed as a carcinoid within a thymus in a MEN type I syndrome. MEN I patients can benefit from the examination with this agent which can potentially localize not only parathyroid endocrine pathology but also unknown associated tumors.
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PMID:Thymic carcinoid and parathyroid hyperplasia detection with 99mTc-MIBI men type 1. 1061 32

We describe a patient presenting with voluminous diarrhoea, hypokalaemic acidosis and hypercalcaemia who was found to have a vasoactive intestinal polypeptide-producing tumour. His diarrhoea was initially mild and intermittent requiring no medical attention.
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PMID:A case of voluminous diarrhoea with hypokalaemic acidosis. 1121 22

Two adult dogs were evaluated for hypercalcemia. Diagnostic evaluation identified elevated parathyroid hormone-related protein (PTHrP) and presumptive humoral hypercalcemia of malignancy. At necropsy, schistosomiasis was diagnosed. North American schistosomiasis is caused by Heterobilharzia americana. Clinical findings may include dermatitis, coughing, diarrhea, and anorexia. Clinicopathological findings may include hypercalcemia, hyperglobulinemia, hypoalbuminemia, anemia, and eosinophilia. Diagnosis by fecal examination is difficult. Praziquantel or fenbendazole treatment may be curative or palliative. These are the first reported cases of hypercalcemia with elevated PTHrP in animals without diagnosed malignancy. Elevation of PTHrP has not been previously reported in hypercalcemic humans or in animals with granulomatous inflammation.
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PMID:Elevated parathyroid hormone-related protein and hypercalcemia in two dogs with schistosomiasis. 1145 Aug 35

Bone recurrence constitutes one third of initial sites of relapse and one half of distant sites of relapse at 10 years from diagnosis of breast cancer. Bone pain, fracture (including vertebral fracture resulting from increased bone resorption following chemotherapy-induced menopause), and hypercalcemia are components of skeletal morbidity. The pathophysiology of malignant osteopathy occurs because of the secretion of substances (such as parathyroid hormone-related peptide), by the malignant cell, which stimulate osteoclast function; this in turn feeds further growth, which causes a vicious cycle. Interruption of this cycle by bisphosphonates may inhibit the growth of malignant cells. Bisphosphonates are drugs that inhibit bone turnover by decreasing bone resorption. Side effects of bisphosphonates include upper gastrointestinal symptoms (in oral nitrogen-containing bisphosphonates) and diarrhea (in oral non-nitrogen-containing bisphosphonates) and an acute phase-like reaction with intravenous (I.V.) pamidronate. Bisphosphonates have different molecular mechanisms of action: Nitrogen-containing bisphosphonates (eg, pamidronate and alendronate) inhibit the mevalonate-signaling pathway while the non-nitrogen-containing drugs (eg, clodronate) incorporate into adenosine triphosphate analogues. There is in vitro evidence that these drugs also possess anticancer properties. In hypercalcemia patients, treatment with pamidronate and zoledronate produce prompt and efficient normocalcemia. Intravenous pamidronate and zoledronate, oral clodronate, and ibandronate reduce skeletal complications in patients with bone metastases; I.V. pamidronate and clodronate are useful for bone pain relief. Three adjuvant bisphosphonate trials are discussed herein: 2 small open-label studies giving conflicting results and a large placebo-controlled trial of oral clodronate. This latter trial shows a reduction in the incidence of skeletal metastases (while the patients are on therapy) and an improved survival at 5 years.
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PMID:Bisphosphonates: biological response modifiers in breast cancer. 1219 79

In June 1999, a 62-year-old man is hospitalised to evaluate the sonographic suspicion of liver metastases. The biopsy of the liver shows a malignant neuroendocrine tumour. Further diagnostic investigation including gastroscopy, colonoscopy, enteroclysis, thoracal and abdominal CT and somatostatin-receptor-scintigraphy does not localise the primary tumour. In the absence of clinical symptoms a wait and see procedure with clinical and imaging controls at regular intervals is arranged. Beginning in spring of 2001--nearly two years after the initial diagnosis--the patient suffers from progredient diarrhoea and weight loss leading to hospitalisation in September 2001. The existence of secretory diarrhoea, hypokalaemia and hypercalcaemia arouses suspicion of vipoma. This is proven by a remarkably elevated plasma concentration of vasoactive intestinal peptide (VIP). Once more, an accurate investigation is started but no primary tumour can be discovered despite extensive liver metastases. A vipoma is a rare differential diagnosis of secretory diarrhoea. This case report describes the remarkable constellation of liver metastases of a malignant neuroendocrine neoplasm without a primary tumour and the clinical presentation of a W.D.H.A. syndrome (watery diarrhoea, hypokalaemia and hypo- or achlorhydria). Despite extensive disease, therapy with octreotide and prednisolone provides a good clinical response.
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PMID:[W.D.H.A. Syndrome due to occult neuroendocrine malignancy with concomitant liver metastases]. 1259 2


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