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 secondary hyperparathyroidism of renal failure is an important component of renal osteodystrophy. We studied PTHmRNA levels and their regulation in control and subtotal nephrectomized (5/6 NX) rats at 3 wk, as well as levels of the 1,25(OH)2D3 receptor mRNA in parathyroids. Serum 1,25(OH)2D levels were decreased in 5/6 NX, whereas PTHmRNA levels were increased (7 +/- 0.7 OD U, N = 4) compared to controls (2.1 +/- 1.2, P less than 0.01); both decreased after 1,25(OH)2D3 (100 pmol/100 g body weight). Similar results were found in 5/6 NX rats after 3 months. There was no change in actin mRNA levels. PTHmRNA levels were highest in 5/6 NX rats with the most severe renal failure. The parathyroid gland 1,25(OH)2D3 receptor mRNA levels were not different between 5/6 NX rats and controls and were not affected by 1,25(OH)2D3 (100 pmol/100 g body weight daily) at 1 or 3 days. PTHmRNA levels of 5/6 NX rats did not increase when the serum calcium was decreased from 2.8 +/- 0.05 mmol/L to 0.9 +/- 0.15 mmol/L at 3 or 5 h, which contrasted with the marked increase in PTHmRNA in normal rats after hypocalcemia. As in normal rats, after hypercalcemia (4.8 mmol/L at 1 h) there was no change in the 5/6 NX rats' PTHmRNA levels. These results show that 5/6 NX rats have increased PTHmRNA levels that are normally regulated by injected 1,25(OH)2D3 but not by calcium. Parathyroid gland 1,25(OH)2D receptor mRNA levels are not increased in 5/6 NX in contrast to the increased PTHmRNA, which reflects the larger glands of uremia. 1,25(OH)2D receptor mRNA levels were not regulated by 1,25(OH)2D3.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of parathyroid cell gene expression in experimental uremia. 210 57

Bisphosphonates (formerly diphosphonates), analogues of endogenous pyrophosphates, are potent inhibitors of osteoclastic bone resorption. While the exact mechanism of action remains poorly understood, etidronate, the only bisphosphonate currently available in the United States for the treatment of hypercalcemia, decreases the elevated serum calcium levels and alleviates the symptoms associated with hypercalcemia of malignancy. Both open and controlled clinical studies have demonstrated that this agent, administered at a dose of 7.5 mg/kg/d in 2-hour intravenous infusions over 3 to 7 days, promotes normocalcemia. In a randomized study, etidronate was shown to be superior to maximally approved doses of calcitonin. Moreover, when administered to patients without overt renal failure (serum creatinine less than 2.5 mg/dL), the drug is remarkably free of significant acute toxicity and side effects. Therefore, an important therapeutic aspect of this agent is that it permits concurrent antibiotic and chemotherapy administration. Judicious use of appropriate and specific pharmacologic intervention strategies in the patient with cancer-related hypercalcemia is expected to enhance quality of life, improve systemic cancer therapy tolerance, and reduce the morbidity of this serious neoplastic complication.
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PMID:Role of the bisphosphonate etidronate in the therapy of cancer-related hypercalcemia. 211 Mar 87

In this problem-oriented review of abnormalities associated with cancer, we have emphasized distinctive diagnostic points related to pathogenesis for each condition and outlined how the approach to management is determined by pathogenesis. For abnormalities of the complete blood count, it is important to distinguish between abnormalities directly related to marrow malignancy and abnormalities associated with extramarrow malignancy. Hemopoietic tumors consist of developmentally deficient blood cells produced by a clonal population of malignant stem cells. Tumors infiltrating marrow cause overcrowding in the limited marrow microenviroment. Extramarrow malignancies cause blood abnormalities, but the potential for normal marrow function is present. Abnormalities of blood cells secondary to therapy are usually clearly identified by consideration of clinical history. The initial differential diagnosis for hypercalcemia is malignancy. An aggressive diagnostic approach may be needed to identify the neoplasm, and therapy should incorporate measures to prevent renal failure. Hypoproteinemia and hyperproteinemia may be caused by neoplasia. Monoclonal gammopathies should be identified and may be associated with hyperviscosity syndrome. Hypoglycemia in the adult animal is most frequently caused by insulin-secreting tumors, but it has also been associated with hepatic and other tumors. Increased blood urea nitrogen, creatinine, lipase, amylase, and liver enzyme activities may also be caused by malignancy. Inadequate urine concentrating ability may be caused by hypercalcemia or malignancy-associated renal insufficiency. Hematuria in older animals is suggestive of urinary tract neoplasia. Exfoliated tumor cells may be identified in the urine sediment of these patients.
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PMID:Laboratory abnormalities in patients with cancer. 219 37

More than a century ago, Jonathan Hutchingson, a surgeon-dermatologist, identified the first case of sarcoidosis at King's College, London. The disease is now known as a commonplace multisystem disorder characterized by the formation of noncaseating granulomata. The diagnosis of sarcoidosis is established by recognizing clinicoradiologic findings and providing histologic evidence of non-caseating granuloma. Serum angiotensin converting enzyme levels are high in about two thirds of the patients and hypercalcemia is a feature in one of every ten victims of sarcoidosis. Immunologic abnormalities include depression of cutaneous delayed-type hypersensitivity, accumulation of T-cells at the site of activity, hyperactive B-cells, and the presence of circulating immune complexes. The course and prognosis of the disease usually correlate with the mode of onset. An acute onset with erythema nodosum indicates a good prognosis and spontaneous resolution; whereas, an insidious onset may be followed by relentless, progressive fibrosis. Mortality and morbidity are caused by pulmonary fibrosis, cardiac arrhythmias, renal failure, neurologic involvement, and blindness. Corticosteroids and chloroquine relieve symptoms and suppress inflammation and granuloma formation.
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PMID:Sarcoidosis. 220 9

Little notice has been paid in the surgical literature to problems with psychoeffective lithium, which by interfering with adenylate cyclase affects thyroid and parathyroid function, causing hypercalcemia, hyperparathyroidism, and hypothyroidism. Seven patients with lithiumogenic hyperparathyroidism occurring after years of lithium therapy underwent treatment and manifested osteoporosis (n = 2), hypertension (n = 2), nephrolithiasis (n = 1), coma (n = 1), rising hypercalcemia (n = 1), goitrous myxedema (n = 4), nephrogenic diabetes insipidus (n = 2), renal failure (n = 2), and hyperlipidemia (n = 1). Disease-directed parathyroidectomy (without morbidity) was curative. Unique laboratory findings included normal serum phosphorus and reduced urinary calcium and cyclic adenosine monophosphate values. Three separate cases of thyroid carcinoma after long-term lithium therapy were also treated, being preceded by myxedema (n = 2) and concurrent with hyperparathyroidism (n = 1). There has been only one previous report of lithium-associated thyroid carcinoma. All patients taking lithium should undergo surveillance for thyroid and parathyroid dysfunction and neoplasia, and appropriate surgical and medical treatment should be considered in each situation. Although hyperparathyroidism may be reversible with lithium discontinuance, such therapy may be obligatory for patient well-being, thus dictating parathyroidectomy.
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PMID:Lithiumogenic disorders of the thyroid and parathyroid glands as surgical disease. 224 24

Multiple myeloma, a generalized malignancy resulting from the proliferation of a single clone of neoplastic plasma cells, occurs rarely in pregnancy. This is the fifth documented case of pregnancy in a woman with this disorder. Clinical features of multiple myeloma include bone pain, pathologic fractures, neurologic deficits, and frequent bacterial infections. Laboratory evaluation often reveals hypercalcemia, anemia, and some degree of renal failure. Both radiation therapy and chemotherapy are used to treat multiple myeloma. Although the ultimate prognosis of a woman with this disease is poor, the offspring are apparently unaffected.
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PMID:Multiple myeloma in pregnancy: a case report. 230 25

Hypercalcemia, due to autonomous functioning of the parathyroids following long standing secondary hyperparathyroidism, is a well known complication in patients with renal osteodystrophy, which can on most cases be treated by parathyroidectomy only. While patients with renal osteodystrophy react favorably to supplementation of active vitamin D metabolites to prevent or reverse renal osteodystrophy, the use of these drugs is bound to result in greater hypercalcemia in those patients who are already hypercalcemic. The question rose if the bisphosphonate amino hydroxypropylidene bisphosphonate (APD) would decrease plasma calcium concentration sufficiently in order to create room for the use of vitamin D to cure the osteomalacia component of the osteodystrophy and simultaneously block the excessive bone resorption. Therefore, five patients with renal osteodystrophy and hypercalcemia were treated for up to 9 months with APD. Three of them, who were on chronic hemodialysis, received 15 mg APD i.v. 3 times a week, the 2 other patients with severe renal failure received 200 mg APD orally. Ionized calcium in plasma did not decrease. Histological investigation of bone samples, obtained before and after therapy, showed an increase of fibrous tissue and a remarkable increase in the number of osteoclasts or osteoclast-like cells not only along the bone-margin, but mainly within the bone-marrow. We conclude that in patients with renal failure with hypercalcemia, APD in the doses used had no effect on plasma calcium level, but caused a striking change in bone histology. Although the consequences of these findings are not yet clear, they do not seem to indicate improvement of bone structure.
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PMID:No effect of APD (amino hydroxypropylidene bisphosphonate) on hypercalcemia in patients with renal osteodystrophy. 233 26

Because of the recently observed augmentation of medullary hypoxic injury by calcium in isolated perfused rat kidneys (Kidney Int 34:186-194, 1988), renal morphology of chronic, prolonged hypercalcemia was investigated in vivo. Rats were treated with repeated injections of vitamin D2 (400,000 units/week) for two to eight weeks. Chronic elevation of plasma calcium from 2.1 to 2.8 mmol/liter (P less than 0.001) was associated by a fall in maximal urine osmolality with no change in glomerular filtration rate. The most significant morphological alterations occurred in the inner stripe of the outer medulla; these changes were characterized by a sequence of active injury with subsequent destruction and atrophy of the medullary thick ascending limbs, fibroblastic and lymphocytic infiltration, and secondary dilatation of collecting ducts. Similar changes occurred in the medullary rays. These alterations were accompanied by increased renal prostanoid production and a predisposition to acute kidney failure from indomethacin. Because of its selective occurrence in zones of poorest oxygen supply, this inner stripe injury may derive from vulnerability to hypoxia and may play a role in some chronic nephropathies.
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PMID:Hypercalcemic nephropathy: chronic disease with predominant medullary inner stripe injury. 234 45

Four case reports are presented which illustrate various patterns of calcific deposits in the heart. Valvular, myocardial, intracavitary, and coronary calcific deposits are illustrated, with emphasis on pathology and clinicopathologic-radiologic correlation. "Dystrophic" and "metastatic" calcifications are terms used to describe calcific deposits in abnormal and normal soft tissues, respectively. These terms are somewhat confusing in relation to the myocardium, however, as the chronologic sequence of cardiac injury is often uncertain. We suggest that these terms be avoided in relation to the heart, in favor of simple descriptive terms such as "myocardial calcific deposits." Many conditions, such as renal failure and hypercalcemia may contribute to the likelihood of soft tissue calcification, although a definite common etiology has not been identified. Likewise, soft tissue calcification has been difficult to diagnose premortem. The advent of ultrafast (cine) computed tomography may provide a quick, noninvasive, highly sensitive and specific method for diagnosis of soft tissue calcific deposits in the future.
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PMID:Calcific deposits in the heart. 235 Sep 14

A 43-year-old patient of occult adult T-cell lymphoma (ATL) presenting with systemic illness and progressive renal failure due to lymphomatous infiltration of kidneys is described. The striking feature observed was destructive infiltration of the kidneys, by malignant CD4 cells, virtually replacing the normal renal architecture. The diagnosis of lymphoma was made by renal biopsy. Clinical features typical of ATL were hypercalcemia, lytic bone lesions, and profound wasting and inanition. The patient died rapidly despite attempted therapy. The case illustrates the potential of ATL for direct renal parenchymal destruction.
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PMID:Progressive renal failure due to renal invasion and parenchymal destruction by adult T-cell lymphoma. 236 8


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