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 murine strain MRL/l spontaneously develops a systemic lupus erythematosus (SLE)-like syndrome. An increased number of T cells and polyclonal T helper cell activity has been described in these mice suggesting a potential role for 1,25-dihydroxyvitamin-D3 [1,25-D3], an antiproliferative hormone selecting the T-helper lymphocyte subset. One month old MRL/l mice were submitted or not to 1,25-D3 0.1 microgram for 4 weeks, then 0.15 microgram given i.p. every other day for 18 weeks while maintained on a low calcium chow. Dermatologic lesions, i.e. alopecia, necrosis of the ear and scab formation, were completely inhibited by 1,25-D3 therapy. By 20 weeks, all mice had developed proteinuria. However, the degree of proteinuria was somewhat reduced in treated mice as assessed by urine protein/creatine ratios (less than 4 vs greater than 4 in treated vs untreated mice respectively). Moreover, a trend for a reduction in serum titers for anti-ssDNA antibodies was observed at 18 weeks. The active vitamin D metabolite had no effect on the development of the generalized lymphoid hyperplasia. Hypercalcemia developed when 1,25-D3 was increased to 0.15 microgram (2.62 +/- 0.12 vs 1.97 +/- 0.07 mmol/l, treated vs untreated mice respectively). These results suggest a beneficial role of 1,25-D3 in the prevention or attenuation of some manifestations of murine SLE, a model sharing many immunologic features with human SLE.
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PMID:1,25-Dihydroxyvitamin D3 attenuates the expression of experimental murine lupus of MRL/l mice. 161 11

The clinical studies about the electrolyte abnormality (EA) in patients with malignant lymphoma (ML) are rarely reported. We analyzed the EA and renal insufficiency in 123 patients with ML between June. 1976 and Jan. 1989; 8 patients with Hodgkin's disease, and 115 patients with non-Hodgkin's lymphoma (NHL). Before treatment, the incidence of the EA was 24.2% and hypercalcemia, hypocalcemia, and hyperkalemia were predominant. After treatment it became to 74.7% and the number of hyponatremia and hypokalemia increased. The incidence of proteinuria and renal insufficiency (serum creatinine above 1.5 mg/dl), were 7.3% and 2.4% before treatment, and became to 26.8% and 26.8% after treatment, respectively. There was a significant difference between two groups with and without the EA before treatment as for serum lactate dehydrogenase (LDH) levels (p less than 0.01), clinical stages (p less than 0.05) and the incidence of bone marrow involvement (p less than 0.01). In 34 autopsied cases, 3 cases showed massive renal involvement and about a half of cases showed various renal changes. The EA before treatment was caused by extrarenal factors, because the incidence of proteinuria and renal insufficiency were almost same to healthy controls. And renal factors play an important role on the E.A after treatment. Above results suggest that the EA before treatment indicates the progress of malignant lymphoma and the EA after treatment means not only the progress of the disease but also therapy-related renal damages.
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PMID:[Electrolyte abnormality and renal insufficiency in malignant lymphoma; clinical and pathological analysis in 123 cases]. 177 51

Monoclonal immunoglobulin deposition occurs in tissues as Congo Red binding fibrils in light chain amyloidosis, as less structured deposits in light chain deposition disease, and as similar but distinct deposits in light and heavy chain deposition disease. The nonamyloid forms were found in 13 patients who had evidence of plasmacytic dyscrasia by the immunohistochemical detection of immunoglobulin light chains of kappa or lambda class (with or without staining for a single heavy chain isotype) and by the absence of amyloid P component in tissue sections that did not show the birefringence characteristic of amyloid after Congo Red staining. All but two of the patients presented with proteinuria with or without azotemia. Clinical syndromes involving other organ systems were less common but occasionally severe. Four patients had overt multiple myeloma. Three others had hypercalcemia and mild bone marrow plasmacytosis but no lytic lesions. Analyses of immunoglobulin synthesis in bone marrow cells from seven patients showed excess light chains in all and incomplete light chains or heavy chain fragments in six, regardless of whether an intact monoclonal protein or related subunit was in the serum or urine. The fibrillar (amyloidotic) and nonfibrillar forms of monoclonal immunoglobulin deposition occur either in overt multiple myeloma or in the course of less neoplastically aggressive plasmacytic dyscrasias. Bone marrow cells from patients with either type produce immunoglobulin fragments that are related to those deposited in the affected tissues.
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PMID:Monoclonal immunoglobulin deposition disease: light chain and light and heavy chain deposition diseases and their relation to light chain amyloidosis. Clinical features, immunopathology, and molecular analysis. 210 17

A chelator, dichloromethane diphosphonate (Cl2MDP), used to treat for malignancy-induced hypercalcemia, has nephrotoxic potential. An acute animal model developed to examine the mechanism was used to further characterize the renal effects. NAG enzymuria appears to be an early premonitor of injury. Ultrastructurally, an increase in size and number of protein-containing phagolysosomal reabsorption droplets in proximal convoluted tubules associated with proteinuria precedes advent of tubular cell necrosis indicating these organelles to be a potential target site for Cl2MDP in the kidney. In vitro studies using rabbit cortical tubules and rat brush border membrane vesicle preparations suggest that the renal toxicity is not due to perturbation of phosphate transport or oxidative metabolism. An operational hypothesis emerges indicating that Cl2MDP may be protein bound affecting carrier protein charge facilitating glomerular leakage with tubular accumulation via protein transport. Cl2MDP may induce critical cation perturbation at the subcellular level as the mechanism of cell death.
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PMID:Characterization of the early ultrastructural and biochemical events occurring in dichloromethane diphosphonate nephrotoxicity. 215 Dec 1

Clinical data of 65 patients with myeloma were analyzed to identify factors associated with hypoalbuminemia. The serum albumin level was not affected by patient age and gender, type of myeloma, and the occurrence of Bence Jones protein, lytic bone lesions, or hypercalcemia, and it was not related to changes in body weight or in liver and renal function. The albumin level, lower in patients with proteinuria, was unrelated to severity of proteinuria. Albumin level correlated significantly with the monoclonal IgG levels, hemoglobin concentration, clinical stage of disease, and estimated body tumor burden. Further analysis indicated the disease stage or the tumor burden as the dominant factor in determining albumin level. An albumin level of 29.0 g/L or less identified unequivocally advanced disease. Practically all patients with stage III myeloma had a serum albumin level of 37.0 g/L or less. Thus, hypoalbuminemia is primarily related to the extent of myeloma proliferation and is therefore of diagnostic and prognostic importance.
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PMID:Hypoalbuminemia in patients with multiple myeloma. 200 Nov 48

Carbetimer (carboxyimamidate) is a low molecular weight derivative of ethylene/maleic anhydride polymer. This compound has demonstrated antitumor activity against several animal models with a daily x 5 schedule appearing most effective. A phase I clinical study of the daily x 5 schedule repeated every 28 days was therefore performed. Forty-one evaluable patients received 66 evaluable cycles of Carbetimer at daily doses ranging from 100-11,000 mg/m2. Hypercalcemia was the dose limiting toxicity with both patients at the 11,000 mg/m2 daily dose level and one patient who received 6 cycles of drug at the 4200 mg/m2 dose level developing severe hypercalcemia not explained by the underlying malignancy. Mild nausea, concentration and rate dependent arm pain at the site of infusion, proteinuria, and coagulopathy were also seen. Calcium balance studies revealed hypercalciuria, suggesting increased mobilization of calcium rather than renal retention. In vitro coagulation studies revealed concentration dependent prolongation of the partial thromboplastin time and thrombin time. No complete or partial responses were seen. However mixed response or biochemical response (reduction in serum lactic dehydrogenase) were seen in 5 patients with melanoma or renal cancer. Due to unacceptable toxicity at the 11,000 mg/m2 daily dose level, Carbetimer 8500 mg/m2 is the recommended dose for a 5-day treatment schedule every 28 days. Special attention should be directed toward possible activity against melanoma and renal cancer.
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PMID:Phase I trial of a 5-day course of carbetimer. 238 16

The pathogenesis, prognosis, and reversibility of renal failure were assessed in 494 consecutive, previously untreated patients with multiple myeloma. For patients with a similar extent of disease, the presence or degree of azotemia did not adversely affect prognosis. Hypercalcemia and/or Bence Jones proteinuria explained the renal failure in 97% of patients. After treatment with a combination of hydration and chemotherapy, normal renal function was achieved in 51% of patients, reversibility usually being rapid and occurring more often in those with slight elevation of serum creatinine. Myeloma control was much more important for survival prolongation than reversal of renal failure, supporting the prompt institution of effective therapy for the underlying malignancy.
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PMID:Renal failure in multiple myeloma. Pathogenesis and prognostic implications. 238 64

Carbetimer, a new synthetic low molecular weight polyelectrolyte with a novel structure displayed antitumor activity in a number of animal tumor model systems and in vitro investigations. Based on these findings it was brought to a phase I clinical trial in patients with advanced malignant disease after failure of conventional treatment or with no conventional treatment available. Forty-eight patients received 98 courses. The schedule was a one hour i.v. infusion every four weeks. The starting dose was 180 mg/m2 and dose escalation was performed according to a modified Fibonacci formula up to 16,690 mg/m2. At least three patients were treated at each dose level and each patient was eligible to receive repeat courses at the same dose, until progressive disease or dose-limiting toxicity intervened. No hematological toxicity was encountered. Some adverse effects such as reversible proteinuria, hypercalcaemia, pain at infusion site, nausea and vomiting and fatigue were seen partly in a dose-related manner but did not represent the maximum tolerated dose (MTD). The limiting toxicity at the highest dose level of 16,690 mg/m2 consisted of ocular symptoms ('light flashes') accompanied by a modest decrease of blood pressure and nausea or vomiting during a one hour infusion. 16,690 mg/m2/1 hour was considered the MTD. There were four deaths on study, all considered disease-related. Fourteen patients had stable disease for more than two courses, which, however, could also be explained by the natural course of disease. No clear-cut antitumor responses were noted in our study center. The recommended dose for phase II trials derived from our results is 12,550 mg/m2/2 hours.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase I trial of the polyelectrolyte carbetimer administered i.v. once every four weeks. 319 84

Diagnosis of multiple myeloma is based on the triad paraproteinemia, osteolytic bone lesions and bone marrow plasma cell infiltration. Clinically, rheumatoid-like pain induced by osteolytic skeletal lesions often prevails. Occasionally, foudroyant bacterial infections - the most frequent cause of death in myelomatosis - or acute/subacute renal failure or rarely, acute hemi- or paraparesis precede diagnosis. Establishment of diagnosis early in the course of the disease and improved cytostatic and symptomatic treatment has led to a decrease in episodes of hyperviscosity-syndromes. Severe renal insufficiency due to Bence-Jones proteinuria prevails in 20% of patients already at time of diagnosis. With increasing duration of the disease, frequency of renal insufficiency further increases. Hypercalcemia with consecutive dehydration and renal insufficiency usually is a complication of long-standing disease. Anemia, leukopenia and thrombo-cytopenia are not only side effects of cytostatic treatment, but also consequences of tumor-induced suppression of hematopoiesis. Polyneuropathies are common in myelomatosis. They probably are the result of specific and/or unspecific binding of paraproteins to myelin sheaths. Effective treatment for this complication is not available at present. Thrombohemorrhagic complications are more frequent in patients with myeloma than in the control group of other hospitalized patients. Non-secretory myeloma, osteoblastic myeloma and Takatsuki syndrome are variants of myelomatosis. Solitary and extramedullary plasmocytoma are different, potentially curable entities. Prognosis is especially poor in patients with plasma cell leukemia and poor in primary amyloidosis.
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PMID:[The clinical picture of multiple myeloma]. 353 47

A patient is described with hypercalcaemia due to myelomatosis without paraproteinaemia or Bence-Jones proteinuria. Immunological investigations yielded some evidence of intra-cellular immunoglobulin production. Histological features suggested the secretion of osteoclast activating factor. Relevant experimental work in support of this interpretation is reviewed.
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PMID:Hypercalcaemia in "non-secretory" myeloma. 354 6


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