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 measured serum concentrations of vitamin D metabolites in 27 patients with myeloma, 16 of whom were hypercalcaemic. Serum values were compared with values from normal controls. Serum concentrations of calcitriol (1.25-dihydroxyvitamin D; 1.25(OH)2D3) were decreased in both hyper- and normocalcaemic patients, but more markedly so in hypercalcaemia. These findings were not solely due to impaired renal function nor due to an inadequate supply of 25-hydroxyvitamin D, and in hypercalcaemic patients were reversed by diphosphonate treatment. We conclude that hypercalcaemia in myeloma is not mediated by abnormalities in vitamin D metabolism. Decreased serum concentrations of 1.25(OH)2D3 may adversely affect both skeletal and tumour metabolism.
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PMID:Vitamin D metabolism in myeloma. 280 79

Thirteen patients with hematological neoplasms were treated with Bestrabucil (100 mg/day po, total dose 700-9,900 mg), which is the benzoate of an estradiol-chlorambucil conjugate. The diseases from which they suffered consisted of T-cell leukemia (3), lymphoma (3), myeloma (5) and essential thrombocytosis (2). Although this drug was less effective against myeloma, the other diseases were more or less relieved with this medication. That is, Bestrabucil was effective in all three patients with T-cell leukemia, both with essential thrombocytosis and two of the three with lymphoma. It is most interesting that adult T-cell leukemia (ATL) cells decreased remarkably with Bestrabucil, along with the disappearance of several symptoms (bone pain, hypercalcemia etc.). The main side effects during this medication were mammary pain (eight of 13 patients, 62%), anorexia (five of 13 patients, 39%) and loss of libido (three of 13 patients, 23%), but neither severe myelosuppression nor hepatorenal dysfunction was induced.
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PMID:[Clinical trial of bestrabucil (KM 2210) in hematopoietic malignancies]. 287 6

A 58-year-old black woman with IgD multiple myeloma developed a hemorrhagic diathesis within 48 hours after receiving mithramycin (20 micrograms/kg/day) for therapy of hypercalcemia. Her coagulation studies were characterized by prolonged prothrombin, partial thromboplastin, thrombin, and reptilase clotting times. Her plasma and partially purified fibrinogen were inhibitory to the clotting of normal plasma and fibrinogen. The patient's isolated fibrinogen showed a normal rate of fibrinopeptide release, but her fibrin monomer aggregation was markedly abnormal. These studies document the development of a dysfibrinogenemia secondary to mithramycin toxicity.
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PMID:Acquired dysfibrinogenemia secondary to mithramycin toxicity. 294 Aug 61

Data concerning the presentation and response to treatment of 73 patients with multiple myeloma who survived for 5 years or more were reviewed. At the time of diagnosis, the proportion of patients with hypercalcaemia (4%), severe anaemia (9%), renal failure (10%) or high beta 2-microglobulin levels (25%) was low. Less than one-third of our patients belonged to a "high risk" group, as defined by the three classification systems adopted: the lowest percentage of such patients (18%) was observed with the Medical Research Council classification. In all patients, but even more in those with an initially aggressive disease (P less than 0.05), obtaining a plateau (70% of the cases) or even an optimal tumoral regression with complete disappearance of monoclonal immunoglobulin (26% of the cases) seems to be a highly favourable factor. The same applies, though to a lesser degree, to slow response to chemotherapy (18 months on average). In all responders whether the remission was maintained or not by chemotherapy seemed to have no influence on the frequency (70%) and delay of relapses (4 1/2 years on average from the time of diagnosis). The risk of secondary blood disease (2 AML 1, 1 AML4, 1 RAEB, 1 ASIA, four of which were directly responsible for death) after 4 years on average of chemotherapy must be taken into consideration.
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PMID:[Prolonged survival in multiple myeloma. Characteristics of presentation and response to treatment of 73 patients who survived 5 years or longer]. 294

We have studied the administration of both oral and intravenous dichloromethylene diphosphonate (Cl2MDP) in patients with hypercalcemia and/or hypercalciuria due to increased bone resorption in the setting of multiple myeloma (N = 16) or chronic lymphocytic leukemia (N = 1). The effectiveness of 1600 mg of oral Cl2MDP twice daily was studied in 14 subjects with refractory multiple myeloma, active osteolytic disease and either persistent hypercalciuria (urinary Ca greater than 200 mg per g creatine on a low Ca intake) or hypercalcemia (serum Ca greater than 11.0 mg/dl), in a double-blind, placebo-controlled, 16 week-long trial. Of the 12 patients who received Cl2MDP (2 died in the placebo phase), 11 had marked reductions in urinary calcium (P less than 0.001), which fell into the normal range in 9. Urinary hydroxyproline decreased significantly in 8. Eight of the 11 responders also appeared to have decreases in bone pain associated with Cl2MDP therapy. Similar results were found when this protocol was used in a study of 10 women with breast cancer metastatic to bone. In addition, intravenous Cl2MDP was studied in 12 patients with hypercalcemia of malignancy, of whom 2 had multiple myeloma and 1 had chronic lymphocytic leukemia (CLL) associated with extensive osteolytic bone destruction. We gave 2.5 mg/kg on the first treatment day and 5 mg/kg daily thereafter for up to six more days. Serum calcium fell to normal after a mean of four days in the three patients with hematologic malignancies as well as in eight of the nine with solid tumors. Both urinary Ca and OHP also declined significantly.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dichloromethylene diphosphonate action in hematologic and other malignancies. 296 56

Increased bone resorption (BR) and increased renal tubular reabsorption of calcium (TRCa) may both be involved in the pathogenesis of hypercalcemia of malignancy (HM). We have evaluated the relative importance of these two mechanisms in 33 patients with HM after extracellular volume expansion and after single infusion of clodronate (C12MDP: 500 mg iv over 8 h). The fasting urine Ca/creatinine ratio was taken as an index of BR (BRI). An index of TRCa was calculated (TRCaI) from a nomogram based on the relationship between urine Ca excretion per unit of glomerular filtration rate and plasma Ca (PCa). Mean (+/- SEM) PCa fell from 3.29 +/- 0.07 to 2.69 +/- 0.05 mmol/l three days after C12MDP (n = 33, p less than 0.001), a response similar to that obtained with repeated daily iv injections of 500 to 1000 mg C12MDP. The pathogenesis of hypercalcemia varied according to the type of neoplasm. BRI was the highest in multiple myeloma and breast tumors. TRCaI was markedly increased in squamous-cells lung, bladder, kidney and liver carcinomas, reaching levels observed in primary hyperparathyroidism. TRCaI was normal in most cases of multiple myeloma. Breast tumors appeared to be heterogeneous with respect to TRCaI. The fall in PCa in response to a single infusion of C12MDP was usually most marked in cancer patients with elevated BRI and normal TRCaI. It was very modest in patients with high TRCaI and slightly elevated BRI. In conclusion, this study confirms that stimulation of bone resorption is not the only mechanism of the maintenance of hypercalcemia of malignancy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bone and renal components in hypercalcemia of malignancy and responses to a single infusion of clodronate. 297 82

The hypercalcaemia of malignancy is multi-factorial, even within individual tumours. In most cases, hypercalcaemia is due to a combination of increased bone resorption associated with decreased renal capacity to excrete the increased extracellular fluid calcium. In solid tumours such as carcinoma of the lung, tumour-derived growth factors are probably primarily responsible for the increased bone resorption, and a separate family of factors which interact with some parathyroid hormone (PTH) receptors cause increased renal tubular calcium reabsorption. PTH production by non-parathyroid tumours rarely if ever occurs. In contrast, haematological malignancies such as myeloma and T-cell lymphomas produce locally acting bone resorbing lymphokines in excessive amounts. Some T-cell lymphomas in addition have the capacity to metabolize 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D. In myeloma, impaired glomerular filtration frequently contributes to the pathogenesis of hypercalcaemia by impairing renal compensatory mechanisms for maintaining normal serum calcium concentrations in the presence of increased bone resorption.
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PMID:Pathogenesis of hypercalcaemia of malignancy. 300 48

The case of a 27 year old patient with IgG-lambda-myeloma is reported. Examination revealed hypercalcemia and acute renal failure. The patient died of heart failure two days after diagnosis. Autopsy revealed an extensive calcification of the inner organs, in particular the heart.
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PMID:[Fulminating course of IgG plasmacytoma at a young age]. 308 20

Renal failure (RF) occurring in the course of multiple myeloma is often judged irreversible and generally considered an ominous complication. The aim of the present study was to re-evaluate the outcome, triggering conditions and prognostic factors of severe RF in a series of 34 patients, 33 to 90 years old. RF was totally reversible in 7 patients and partially reversible in 9 although 6 of them had to be temporarily dialyzed. However, the improvement in renal function was often very slow as indicated by an average recovery time of 115 days. The high rate of RF reversibility was associated with markedly lengthened survival. Review of triggering events confirmed the leading role of dehydration and hypercalcemia, but further suggested that intake of nonsteroidal anti-inflammatory drugs and renal infection might play a part in the development of RF. Systematic statistical analysis of potential prognostic factors showed that the outcome was significantly more severe in females, but age, myeloma characteristics including tumor mass, calcemia, and triggering events had no predictive value. The most reliable prognostic indicators were provided by analysis of kidney biopsy performed in 30 patients. Complete recovery from RF was observed only in the absence of global tubular atrophy and interstitial damage. In contrast, cast-induced tubular obstruction detected by the presence of Tamm-Horsfall protein in urinary space of glomeruli did not seem to influence the outcome of RF. Finally, we analyzed the prognostic value of immunochemical properties of light chains (LC). Lambda LC were unexpectedly detected in 2 of 3 patients, as compared to a ratio of 1 to 3 in the population of normal and monoclonal Ig, but LC type did not correlate with the course of RF. Isoelectric points of LC measured in 32 patients were dispersed from 5.2 to 8.9 and bore only weak prognostic significance. These results underline the value of kidney biopsy and justify aggressive treatment including dialysis and chemotherapy.
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PMID:Multiple myeloma and severe renal failure: a clinicopathologic study of outcome and prognosis in 34 patients. 310 93

A 53-year-old male with Bence Jones lambda myeloma developed hypercalcemia and acute renal failure (calcium 14.4 mg/dl, BUN 40 mg/dl, creatinine 3.0 mg/dl) after initial response to chemotherapy. A 99mTc-MDP bone scan revealed unusual isotope accumulation in the left hypochondrium. Extensive calcium deposition was confirmed in the gastric mucosa in the postmortem examination. Detection of gastric calcification by a bone scan is very rare. Only two cases of gastric calcification visualized on bone scans can be found in the literature, one with multiple myeloma) and one in Hodgkin's disease).
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PMID:Metastatic calcification in the stomach demonstrated by a bone scan in Bence Jones lambda myeloma. 310 83


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