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 occurrence of a monoclonal gammopathy followed by IgG-lambda multiple myeloma is described in a patient receiving diphenylhydantoin therapy for 20 years for epilepsy. Despite the known association between the drug and the development of immunosuppression and lymphoma, we regard the association recorded in this case to be coincidence. It is suggested that periodic examination of the serum proteins in patients receiving the drug may be useful in detecting early aberrations of the immune system in these individuals.
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PMID:Myelomatosis after phenytoin therapy: a chance association? 10 87

The development of an IgG lambda-type monoclonal gammopathy and subsequent multiple myeloma in an epilepsy patient on diphenylhydantoin (DILANTIN) therapy for 20 years is reported. We regard the association recorded in this case to be a coincidence despite the known association between the drug and the development of immunosuppression and lymphoma. We recommended periodic examination of the serum proteins in patients receiving diphenylhydantoin in order to detect development of monoclonal gammopathy.
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PMID:Monoclonal gammopathy and subsequent multiple myeloma in a patient on chronic diphenylhydantoin therapy. 74 38

During the last few years the use of intravenous immunoglobulin (IVIG) has attracted increasing interest for the treatment of patients who do not have a classical humoral antibody deficiency syndrome. In certain situations this approach has revolutionized medical management, e.g. in immune thrombocytopenia. In other areas, such as in Kawasaki's syndrome, IVIG therapy have been shown to be highly beneficial in preventing long term disease sequelae by some investigators, but the field remains controversial. Conditions under which IVIG therapy has been shown to be of potential benefit are: (1) intractable childhood epilepsy; (2) autoimmune diseases, e.g. myasthenia gravis, systemic lupus erythematosus, idiopathic thrombocytopenic purpura, idiopathic neutropenia and aplastic anemia; (3) atopic allergy with IgG subclass deficiency including bronchial asthma; (4) in severe infections in combination therapy with antibiotics and as an antipyretic; (5) in Kawasaki's disease; (6) in multiple myeloma and chronic lymphocytic leukemia. Oral and intraventricular administration of IVIG have also been tried, the former for severe diarrhea and the latter to try to rescue the central nervous system from damage by a pathogen. Carefully controlled clinical trials are needed to establish the efficacy of gamma-globulin therapy in these and other conditions.
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PMID:New and controversial uses of intravenous gamma-globulin. 245 9

A confusional state due to hypercalcemia led to the discovery of multiple myeloma in a 73 year old man. The recurrence of a confusional state, related to plasma cell meningitis called for hospitalization. Serum, urine and cerebrospinal fluid immunoelectrophoresis revealed monoclonal immunoglobulines of lambda light chains. The pathologic study showed an invasion of the subarachnoid space by abnormal plasma cells. The dura mater and brain substance were not invaded. The leptomeningeal invasion by multiple myeloma plasma cells in a rare occurrence. We have found only three such cases published before. The analysis of our case and the three other leads to some comment. The clinical features are those of chronic meningitis revealed by a confusional study or epilepsy. The existence of abnormal plasma cells in the cerebrospinal fluid and their absence in the blood stream seems to suggest a local production of these cells. The histopathological study confirmed, in our case as in the others published, the massive invasion of the subarachnoid space by plasma cells while the dura mater is not invaded.
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PMID:[Plasmocytic meningitis in multiple myeloma. An anatomo-clinical observation]. 688

In 1974 and 1975 7000 patients' sera were tested for levels of IgG, IgA and IgM. In 330 patients at least one of the three Ig classes was low. In most instances secondary immunodeficiency was present in association with myeloma, etc. However, 81 patients above 8 years of age fulfilled the criteria of idiopathic late onset Ig deficiency. In 44 of these patients clinical follow-up and repeated measurements of Ig levels were possible 1--8 years after the initial diagnosis. Selective IgA deficiency was present initially (15 patients) most frequently and persisted most often (14 patients). 4 patients had initially low IgG and 6 patients low IgM, findings which were only rarely confirmed later on. In 19 patients 2 or 3 Ig classes were initially low, with persistence of Ig deficiency in 12 individuals. In no instance had clinical symptoms appeared in the first two years of life. The following diseases were documented in the 44 patients studied (28 individuals with persistent and 16 with transitory Ig deficiency): recurrent infections (16 patients), atopic disease (8 times), rheumatoid arthritis (6 times), epilepsy (4 times), SLE (3 times) and enteropathies (twice). Seven patients also had a malignancy, 4 diabetes, and 2 hyperthyroidism.
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PMID:[Idiopathic immunoglobulin deficiency in juveniles and adults. Catamnestic studies]. 739 75

Immune abnormalities have been found in many patients receiving anti-epileptic drugs. However, the effects of carbamazepine are still conflicting. We report the case of a 31-year-old woman who began carbamazepine treatment because of idiopathic epilepsy of adulthood. After three years of treatment she developed arthralgias and malaise. Complete immunologic evaluation showed a total absence of immunoglobulin M with decreased levels of immunoglobulin A, positive antinuclear antibodies and monoclonal paraproteinemia type IgG-kappa. The possibility of B cell lymphoma or myeloma was ruled out. Skin testing was negative. Bone marrow examination was normal. After carbamazepine discontinuation, levels of IgA and IgM increased until reaching normal values over 3 years. The monoclonal gammopathy of undetermined significance also disappeared over this period. During this period of immunodeficiency, the patient did not complain of any infectious complications.
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PMID:Carbamazepine induced transient monoclonal gammopathy and immunodeficiency. 1508 96

There has been considerable debate about the relationship between epilepsy and cancer, in particular whether the incidence of cancer is increased in people with epilepsy and whether antiepileptic drugs promote or protect against cancer. We review available evidence from animal experiments, genotoxicity studies and clinico-epidemiological observations, and discuss proposed mechanisms underlying the association between epilepsy and cancer. A carcinoma-promoting effect has been seen unequivocally in rodent models for phenobarbital and phenytoin; phenobarbital promoted liver tumours and phenytoin caused lymphoid cell and liver tumours in rats. Early human epidemiological studies found an association between phenobarbital and hepatocellular carcinoma, and several subsequent studies suggested an association with lung cancer. An association with brain tumours has also been demonstrated. Phenytoin has been causally implicated in three human cancers: lymphoma, myeloma and neuroblastoma, the latter specifically in the setting of foetal hydantoin syndrome. However, despite considerable long-term pharmaco-epidemiological data being available for both antiepileptic drugs, evidence for human carcinogenicity is not consistent and both are considered only possibly carcinogenic to humans. Valproate, however, has been found to exert an antiproliferative effect on certain cancer cell lines both in vitro and in vivo. A corresponding cancer-suppressive effect has not been studied in human epidemiological studies, though there are now preliminary reports of the use of valproate in human haematological and solid tumours. The anticancer activity of valproate appears to be driven by histone deacetylase inhibition and to be independent of hormone or multidrug protein resistance dependent mechanisms. The newer antiepileptic drugs appear to be safe, as no carcinogenicity has been demonstrated either during regulatory testing or in post-marketing surveillance. Nevertheless, the subject of cancers and epilepsy constitutes a promising agenda for clinical and experimental research in the future.
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PMID:Cancer risk in people with epilepsy: the role of antiepileptic drugs. 1557 65

Multiple myeloma (MM) is an incurable hematological disorder characterized by dysregulated proliferation of terminally differentiated plasma cells. Aberrant histone acetylation has been observed in the development of numerous malignancies. Histone deacetylase inhibitors such as valproic acid (VPA) are promising drugs for cancer therapy since they have been reported to have antiproliferative effects and to induce differentiation in carcinoma and leukemic cells. Considering the advantage of being already in clinical use for epilepsy treatment, valproic acid might be a promising therapeutic candidate drug in the management of multiple myeloma. In this study, we show that the short fatty acid VPA has a time and dose-dependent cytotoxic effect on the MM cell lines OPM2, RPMI and U266. The influence of VPA on cell cycle and apoptosis have been evaluated by flow cytometry. Our results show that the three cell lines are blocked in G0/G1 phase. The observed sensitivity to VPA can be partially explained by late apoptosis. Since caspase 3 is activated in all tested cell lines after VPA treatment, a caspase-dependent pathway seems to be involved but not activated by the classic apoptotic pathways. We have also studied another mechanism of cell death, the senescence-like phenotype, but did not find any evidence for its implication. Thus, treatment with VPA may imply other alternative cell death mechanisms.
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PMID:Valproic acid induces non-apoptotic cell death mechanisms in multiple myeloma cell lines. 1727 58

Multiple myeloma is still an incurable disease, most commonly occurring in the elderly. The myeloma-induced bone marrow microenvironment protects myeloma cells from drug-induced apoptosis. Therefore, the development of novel and tolerable therapeutic alternatives to overcome the drug resistance is an important clinical issue. Valproic acid (VPA), a safe and widely used anti-epileptic agent, is revisited as a class I- and IIa-specific histone deacetylase inhibitor. In the present study, we evaluated the effect as well as a mechanism of actions of VPA on myeloma cell growth and survival, with special reference to the myeloma-induced bone marrow microenvironment. VPA at therapeutic concentrations for epilepsy induced cell death in primary CD138-positive myeloma cells as well as myeloma cell lines, but not in CD138-negative bone marrow cells. VPA suppressed osteoclastogenesis as well as osteoclast-mediated myeloma cell growth. VPA also inhibited vascular tubule formation enhanced by co-cultures of myeloma cells and osteoclasts in concert with thalidomide. In addition, VPA induced both caspase-dependent and -independent cell death in myeloma cells, and potentiated the anti-myeloma effects of melphalan and dexamethasone. Collectively, VPA is suggested to exert multi-factorial anti-myeloma actions, and may serve as a safe adjuvant to be included in conventional chemotherapies against myeloma.
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PMID:Valproic acid exerts anti-tumor as well as anti-angiogenic effects on myeloma. 1909 63

Multiple myeloma, a rare cancer for individuals less than 65 years of age, and its pathophysiological effects have a profound impact on neurocognitive function. Specific transient deficits in patients with renal failure secondary to multiple myeloma have been noted to improve with hemodialysis. We present a complex case of an individual with multiple myeloma, renal insufficiency, treated seizure disorder, and schizophrenia, paranoid type, who experienced functional improvements in memory and visuospatial function with short- and long-term administration of hemodialysis. Within weeks of treatment, memory impairments resolved. With continued hemodialysis, some areas of neurocognitive function were in the superior range, indicating an overall improvement of more than three standard deviations. Implications and recommendations for clinicians treating individuals with similar challenges are offered.
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PMID:Effects of hemodialysis on profound memory deficits in renal insufficiency due to multiple myeloma: a case study. 1920 51


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