Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The detection of Bence Jones protein, an important part of the investigation of suspected myeloma, is most commonly done by agarose or cellulose nitrate electrophoresis followed by immunofixation. Bence Jones protein is recognized as single or multiple bands of one type of light chain. Unfortunately, improvements in sensitivity of these techniques (use of high-affinity antisera and higher resolution electrophoresis) frequently allow detection of multiple light chain bands in the urine of patients who do not have a B-cell dyscrasia. The bands are usually kappa, although they may be accompanied by lambda bands. This pattern may lead to the misdiagnosis of Bence Jones protein and oligoclonal light chain production in patients. Here we show that this pattern is produced by polyclonal light chains; it is present in the urine of all patients with a tubular proteinuria of any etiology and may be induced in healthy individuals by blocking their renal tubular protein reabsorption. Polyclonal light chains separate into monomers and dimers on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and into four major bands with many minor bands by isoelectric focusing. This difference in charge and possibly size results in the banding pattern seen on good-quality electrophoresis and immunofixation.
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PMID:Restricted electrophoretic heterogeneity of immunoglobulin light chains in urine: a cause for confusion with Bence Jones protein. 190 42

Three patients presented with encephalopathies: an undiagnosed degenerative disease of the brain, a degenerative cerebral disease in a patient with a myeloma but without a myelomatous deposit in the CNS and a malignant astrocytoma. Perivascular pallidal deposits (vascular siderosis) containing chromium, phosphorus and calcium plus sometimes traces of other elements were present in the three cases. Such deposits were present in the pallidal parenchyma and around vessels in the cerebellum in one case. Calcium and phosphorus are always present in any CNS calcification but the presence of chromium has not been reported. Chromium and its compounds (ingested, injected or inhaled) are toxic to humans and animals in trace doses. Approximately 900 cases of chromium intoxication have been reported and usually have had dermatological or pulmonary lesions (including cancer) but there is no report of involvement of the CNS. Sublethal doses of chromium nitrate injected intraperitoneally in rats and rabbits results in the presence of chromium in the brain. A thorough investigation was made to find the source of the chromium in these patients. Chromium was found to be present in trace amounts in the radiological contrast agents administered to these patients and in the KCl replacement solution and in mylanta, an antacid, given to one case. The evidence that chromium induced pathological changes in these three brains is circumstantial but shows that chromium can penetrate the human brain. This study indicates that vascular siderosis found in the brains of the majority of middle-aged and elderly humans is not simply an anecdotal pathological curiosity, but that it can serve as a route of entry for toxic products into the brain.
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PMID:Abnormal deposits of chromium in the pathological human brain. 395 42

Analytical IEF, immunofixation, and silver nitrate staining of mouse monoclonal, human myeloma, and multiple sclerosis (MS) oligoclonal IgG result in multiple bands. Because the IgG secreted by mouse hybridoma and multiple myeloma are the products of single clones of cells, it is reasonable to propose that MS CSF IgG multiple bands may be derived from one or a small number of clones of IgG secretors.
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PMID:Hypothesis: multiple sclerosis cerebrospinal fluid IgG multiple bands are derived from one or a few IgG secretor cell clones. 671 29

We have studied 72 cases of multiple myeloma (MM) bone marrow trephine biopsies using the monoclonal antibody PC-10 and the colloid silver nitrate method for identification of proliferating cell nuclear antigen (PCNA) and nucleolar organizer regions (NORs), respectively. PC-10 and AgNOR scores were statistically significantly different between low versus intermediate and low versus high grade of malignancy (P < 0.001), whereas their difference was not significant between intermediate and high grade. A strong correlation was identified between these two proliferation-associated indices in each histological grade. There is evidence that the proliferative state of myelomas belonging to the intermediate grade is approximately the same as that observed in high grade (blastic) ones.
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PMID:Expression of proliferating cell nuclear antigen (PCNA) and nucleolar organizer regions (NORs) in multiple myeloma. 791 7

Gallium nitrate was originally developed as an antineoplastic agent; however, further studies have revealed that this drug has extremely potent effects on turnover of bone, and that low doses can be used to reduce bone resorption. Like the bisphosphonates, gallium nitrate has been studied in both malignant and in nonmalignant conditions. The results of randomized double blind studies have suggested that this drug has superior clinical efficacy relative to etidronate, calcitonin, and pamidronate for the acute control of cancer-related hypercalcemia. In patients with Paget's disease, low doses of gallium nitrate reduce biochemical parameters of accelerated bone turnover, including urinary excretion of calcium, hydroxyproline, and urinary collagen cross-linked N-telopeptides. Preliminary studies showed similar effects in patients with bone involvement from a wide variety of tumor types. Based on this high degree of clinical potency revealed in clinical studies, two randomized Phase III studies have been initiated in patients with bone metastases from breast carcinoma and bone involvement due to multiple myeloma. Both studies employ cyclic therapy with low dose gallium nitrate (i.e., 40 mg administered as a subcutaneous injection once daily for 2 weeks, followed by 2 weeks off treatment, recycled monthly). The endpoints of both studies are to document reductions in time to "morbid skeletal events," such as palliative skeletal radiotherapy, stabilizing orthopedic surgery, or pathologic fractures, as well as decreases in pain and analgesic requirements and improvements in mobility and other aspects of quality of life. These trials should provide definitive evidence of whether this agent is safe and effective as a treatment for bone metastases.
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PMID:Gallium nitrate for the treatment of bone metastases. 936 36

Adjunctive anti-bone resorption therapy has become an important part of multiple myeloma (MM) treatment. Currently, no definite evidence exists that this therapy increases survival. We examined a cohort of 13 of 167 patients (8%) treated with the M-2 protocol who received adjuvant gallium nitrate (GN) treatment for osteolysis, and then compared the outcome of these patients to all individuals treated with the M-2 regimen. The stage at diagnosis was IA in two patients, IIIA in 10 patients and IIIB in one. Median age at diagnosis was 51 years (range 35-73). Median (range) of entry data were: paraprotein level: 6000mg/dl (3058-8675); beta2M: 2.7mg/l, (1.2-9.6); LDH: 166U/l (142-237); hemoglobin: 10.2 g/dl (8.3-12.6); albumin: 3.7 g/dl (2.5-5.0); calcium: 10.0 mg/dl (8.3-14.5); creatinine: 1.2 mg/dl (0.7-2.7). Median survival in these patients was 87+ months from time of diagnosis compared with 48 months for all other patients treated on the M-2 protocol. We identified a subgroup of patients with remarkably prolonged survival who had received M-2 chemotherapy and GN. Survival in this group markedly exceeds expectations for patients with advanced stage disease and poor prognostic features. The administration of GN may have a positive impact on survival either by decreasing skeletal complications or through a direct action of GN on the complex cytokine network involved in the proliferation of the malignant myeloma cell.
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PMID:Extended survival in advanced-stage multiple myeloma patients treated with gallium nitrate. 1200 65

Gallium nitrate, the nitrate salt of the "near-metal" element gallium, is highly effective in the treatment of cancer-related hypercalcemia. Unlike bisphosphonates, gallium nitrate is effective in both parathyroid hormone-related protein-mediated and non-parathyroid hormone-related protein-mediated hypercalcemia. Gallium nitrate's effects on bone are clearly different from those of bisphosphonates. Gallium nitrate enhances calcium and phosphate content of bone and has direct, noncytotoxic effects on osteoclasts at markedly lower doses than those used for the treatment of cancer-related hypercalcemia. The drug may have clinical application in a variety of disorders associated with accelerated bone loss, including multiple myeloma. Gallium nitrate was originally evaluated as an antitumor agent. Its antitumor activity occurs at somewhat higher doses than those used in the treatment of cancer-related hypercalcemia. Gallium nitrate has substantial single-agent activity in the treatment of advanced lymphoma, particularly diffuse large cell lymphoma, small lymphocytic lymphoma, and follicular lymphoma. Because of its profile, including a different mechanism of action and minimal myelosuppression, the drug merits further evaluation in the treatment of advanced lymphoma. Gallium nitrate also has activity in advanced bladder cancer and may be useful in patients with metastatic or unresectable disease failing first-line chemotherapy regimens. Gallium nitrate exhibits a range of dose-dependent pharmacologic actions that provide a basis for its therapeutic potential in a variety of diseases and warrants further investigational evaluation as an antiresorptive and antitumor agent.
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PMID:Gallium nitrate revisited. 1277 53

Gallium nitrate has been shown to be an effective treatment for patients with cancer-related hypercalcemia. Clinical studies have also suggested the drug may have considerably broader use in other diseases associated with accelerated bone loss including multiple myeloma, bone metastases, Paget's disease, and osteoporosis. The actions of gallium nitrate on bone are quite distinct from those of bisphosphonates. Preclinical studies show that gallium preferentially accumulates in trace amounts in metabolically active regions of bone. When present, gallium favorably alters the mineral properties to enhance hydroxyapatite crystallization and reduce mineral solubility. The drug also acts on the cellular components of bone to reduce bone resorption by decreasing acid secretion by osteoclasts. This effect appears to be mediated by inhibition of the ATPase-dependent proton pump of the osteoclast's ruffled membrane. Gallium does not inhibit the development or recruitment of osteoclasts to bone tissue, unlike many bisphosphonates that may induce osteoclast apoptosis. Together, these pharmacologic actions may yield a skeletal system with increased calcium and phosphate content and improved biomechanical strength. Gallium nitrate has potent antiresorptive effects on bone that can be achieved at considerably lower doses than are currently used for cancer-related hypercalcemia. Parenteral and oral formulations of gallium appear to have high activity in bone resorptive disorders, and thus development should be vigorously pursued in these diseases.
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PMID:The effects of gallium nitrate on bone resorption. 1277 54

Multiple myeloma is characterized by bone destruction mediated by osteoclastic bone resorption. Skeletal complications of myeloma, including bone pain, fractures, spinal cord compression and hypercalcemia, result in significant morbidity. Gallium nitrate was shown in a small, randomized trial to attenuate the rate of bone loss in patients with myeloma treated with chemotherapy. In a retrospective analysis, we found that patients with advanced multiple myeloma treated with chemotherapy plus gallium nitrate had markedly prolonged median survival compared with similar patients treated with chemotherapy alone (87+ months v 48 months, respectively). These data suggest that gallium nitrate may have a positive, indirect benefit on survival in myeloma by decreasing the rate of bone resorption. Further evaluation of gallium nitrate to attenuate progression of disease in patients with multiple myeloma is warranted.
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PMID:Gallium nitrate in multiple myeloma: prolonged survival in a cohort of patients with advanced-stage disease. 1277 56

We propose ICA-L, a wetland physicochemical water quality index (WWQI), to be used as a management tool for seasonal-flooding lagoons in Palo Verde National Park, Guanacaste, Costa Rica. The goal is to preserve their natural role for native plants as well as migrants and local animal species. The index was developed in four steps: parameter selection, assignment of parameter weight, transformation of data to their corresponding sub indices and selection of an appropriate aggregation function. In this process, the following criteria were used as a reference: WQI from the National Sanitation Foundation, WQI for the Des Moines River, Escribano and De Frutos WQI, the international legislation on maximum acceptable concentration for different water quality variables, and the authors' personal criteria. The index includes the following parameters: dissolved oxygen percent saturation, pH, nitrate concentration, total phosphorus concentration, chemical oxygen demand, concentration of suspended solids, electrical conductivity and temperature. The index sets itself to zero if the concentration of some toxic substance exceeds the maximum allowed limit. The adjustment values were based on "weights" defined in the National Sanitation Foundation Water quality Index (ICA-NSF). In this study, the weight of fecal coliforms count was excluded, the values of turbidity and the one for total solids were integrated into one (suspended solids) and a factor of 0.08 was assigned to the conductivity parameter. The sub indices associated to suspended solids were obtained from the quality of Kahler-Royer variation graph; the values for pH and the nitrate concentration from the graphs constructed for ICA-NSF. The percentage of dissolved oxygen saturation, in sites like irrigation channels, was evaluated directly from the quality variation graph constructed for ICA-NSF, whereas the same parameter for the flooding lagoons required an adjustment based on the optimal value for similar non contaminated ecosystems. The conductivity was evaluated from adjustments in the qualification functions commented by Escribano & De Frutos. Chemical oxygen demand, total phosphorus and temperature, were qualified based on the functions developed for the ICA-L.
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PMID:[Physicochemical water quality index, a management tool for tropical-flooding lagoons]. 1941 91


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