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 describe a neonate with distal renal tubular acidosis with secondary hyperparathyroidism manifesting as hyperchloraemia, hypercalcaemia, elevated serum parathyroid hormone (PTH) and life-threatening metabolic acidosis. He exhibited general weakness, tachypnoea, dry skin and weight loss. Urinary excretion of titratable acid and ammonium was decreased. Daily alkali (2.5 mEq/kg body weight) was required to maintain a normal plasma bicarbonate (HCO3-). With alkali therapy, the fractional excretion of HCO3- was below 5%. Serum calcium and PTH were restored to normal promptly on initiation of alkali therapy. After 5 months of alkali therapy, normal growth and urine acidifying ability were restored and alkali therapy was discontinued. The acidification defect in this patient was transient. We consider this patient to be consistent with Lightwood's syndrome of "transient infantile renal tubular acidosis".
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PMID:Transient neonatal distal renal tubular acidosis with secondary hyperparathyroidism. 161 37

Studies have suggested that both natural and synthetic retinoids have extensive chemopreventive activity against a variety of carcinogens in vivo and in vitro. We have previously shown that growth of human breast cancer cells can be inhibited by retinoids, and retinoic acid-binding proteins have been demonstrated in these cell lines and tumor biopsies. We studied the activity of 13-cis-retinoic acid in the treatment of 18 patients with advanced breast cancer refractory to standard cytotoxic and/or endocrine therapy. Patients began on 0.5 mg/kg and escalated to 8 mg/kg over a one-month period unless toxicity (dry skin, dry mucosa, cheilitis, conjunctivitis) forced dose reduction. All these toxicities responded promptly to dose reduction. Four patients exhibited drug related hypercalcemia, 2 complained of severe earache and several had nausea, vomiting and abdominal cramping. There were no objective responses as defined by standard criteria. One patient with thrombocytopenia secondary to documented marrow involvement demonstrated a recovery of platelet count from 9000 to 110,000. 13-cis-Retinoic acid is not of apparent value in women with heavily pretreated breast cancer.
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PMID:Phase II trial of 13-cis-retinoic acid in metastatic breast cancer. 696 67

Retinoids are commonly used for the treatment of nonmalignant skin disorders and occasionally for the treatment of various neoplasms including epidemic Kaposi sarcoma (KS). Dry skin and mucus membranes, muscle and joint aches, alopecia, headaches, and liver and lipid abnormalities are the most frequent medication-related side effects. Very rarely, this class of drugs is associated with the development of hypercalcemia. The authors report the case of a man with acquired immunodeficiency syndrome (AIDS)-associated KS who, while participating in a phase II clinical trial of LGD 1057 (9-cis-retinoic acid) for treatment of epidemic KS, developed hypercalcemia, mental status changes, and renal insufficiency. The etiologic factors of retinoid-induced hypercalcemia are imperfectly understood, but with drug withdrawal his serum calcium, mental acuity, and renal function quickly normalized. Hypercalcemia occurs infrequently in the setting of AIDS and when present, is usually mediated by opportunistic infections. Clinicians should be alert to this potentially life-threatening iatrogenic complication that responds favorably to drug withdrawal.
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PMID:Retinoid-induced hypercalcemia in a patient with kaposi sarcoma associated with acquired immunodeficiency syndrome. 978 12

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

We conducted a phase II study to determine the efficacy and toxicity of 9-cis-retinoic acid (9-cis RA), a pan-retinoid receptor agonist, in the treatment of patients with relapsed and refractory NHL. Patients were eligible if they had histologically documented relapsed or refractory T cell or indolent B cell NHL. The first three patients enrolled received 70 mg/m2 of 9-cis RA orally twice a day, but the remaining patients received a single oral daily dose of 100 mg/m2. After 6 weeks of therapy, tumor response was assessed objectively. Response rate and toxicity were determined in all 29 eligible patients based on an intent-to-treat analysis. Four patients (14%) responded (3 PRs and 1 CR; 95% CI 4%-33%). One patient had a minor response, and eight had stable disease. Responses were observed in two (11%) of 19 patients with B-cell lymphoma and in two (20%) of 10 patients with T-cell lymphoma. The median time-to-treatment failure for the 29 eligible patients was 8 weeks. The most frequent toxic effects were dry skin, headache, hypertriglyceridemia, and hypercalcemia. Five patients discontinued therapy due to toxic side effects, but no toxic deaths occurred during the study. We conclude that 9-cis RA has a modest activity in relapsed and refractory NHL. In this study, responses were observed in patients with B-cell lymphomas and those with T-cell lymphomas.
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PMID:Experience with 9-cis retinoic acid in patients with relapsed and refractory non-Hodgkin's lymphoma. 1142 31