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)

Simple bedside measurements of blood pressure and systolic pressure response to the Valsalva maneuver will confirm a clinical impression of orthostatic hypotension. Careful questioning of the patient usually elicits other symptoms of autonomic nervous system dysfunction, such as impotence, urinary and fecal incontinence, constipation or diarrhea, blurred vision, or sweating changes. Drugs are the most common cause of autonomic dysfunction, and their benefits should be weighed against the severity of the dysfunction. In addition, diabetes mellitus, uremia, amyloidosis, acute intermittent porphyria, myeloma, tabes dorsalis, and alcohol-nutritional problems may produce symptoms of autonomic dysfunction. Thus, patients who present with autonomic features but no history of dysfunction-producing drugs should undergo complete laboratory evaluation. A regimen of tyramine or L-dopa or a diet rich in cheese, processed meats, and wine (a monoamine), coupled with a monoamine oxidase inhibitor have beneficial effects in patients with orthostatic hypotension due to preganglionic autonomic dysfunction. Patients who do not respond to catecholamine precursors have stable, isolated orthostatic hypotension or a polyneuropathy such as that caused by diabetes.
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PMID:Evaluating dysfunction of the autonomic nervous system. 63 67

Fludarabine phosphate is the 2-fluoro, 5'-monophosphate derivative of vidarabine (ara-A) with the advantages of resistance to deamination by adenosine deaminase (ADA) and improved solubility. The mechanism of cytotoxic action of the compound appears to involve metabolic conversion to the active triphosphate. Fludarabine phosphate has substantial activity against lymphoid malignancies, particularly chronic lymphocytic leukemia (CLL) and low-grade non-Hodgkin's lymphoma (NHL). Its single-agent activity in CLL appears at least comparable to those of other conventional combination regimens. Its activity in Hodgkin's disease, mycosis fungoides, and macroglobulinemia, although suggestive, needs to be further defined and clinical trials are warranted in hairy cell leukemia, prolymphocytic leukemia, and previously untreated myeloma. The compound does not appear active against most common solid tumors. Early clinical trials indicated significant myelosuppression and the potential for severe neurotoxicity. Toxicity on the currently used low-dose schedules includes transient and reversible myelosuppression, nausea and vomiting, diarrhea, somnolence/fatigue, and elevations of liver enzymes and/or serum creatinine. Possible pulmonary toxicity has been suggested in several patients. The currently used low-doses of fludarabine phosphate, even with repeated administration, are well tolerated and appear safe with a negligible risk for severe neurotoxicity. Based on its single-agent activity and tolerability, the Food and Drug Administration recently granted group C designation of the drug for the treatment of patients with refractory CLL outside the clinical trials setting. The use of fludarabine phosphate in combination regimens and its impact on the natural history of the lymphoid malignancies is yet to be determined. Fludarabine phosphate may well occupy a pivotal role in the management of CLL and low-grade NHL.
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PMID:Fludarabine phosphate: a synthetic purine antimetabolite with significant activity against lymphoid malignancies. 170 43

Autologous bone marrow transplantation (ABMT) for advanced hematologic malignancies is associated with high relapse rates. Interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells represent a potentially non-cross-resistant therapeutic modality that might prevent or delay relapses if used early after ABMT at a time when the tumor burden is minimal. However, high-dose chemoradiotherapy and ABMT might increase patients' susceptibility to IL-2 toxicity, and might interfere with immunologic responses to IL-2 in vivo. Therefore, to determine safety, tolerance, and immunomodulatory effects of IL-2 therapy early after ABMT, IL-2 was administered by continuous intravenous infusion to 16 patients 14 to 91 days (median, 33) after ABMT for acute leukemia, lymphoma, or multiple myeloma. Patients were sequentially assigned to escalating IL-2 "induction" doses (0.3 to 4.5 x 10(6) U/m2/d, days 1 to 5), and all patients received a nonescalating IL-2 "maintenance" dose (0.3 x 10(6) U/m2/d, days 12 to 21). Most patients exhibited mild to moderate fever, nausea, diarrhea, and/or skin rash with IL-2 infusions. The maximum tolerated "induction" dose was 3.0 x 10(6) U/m2/d; dose-limiting toxicities were hypotension and thrombocytopenia. All toxicities reversed on stopping the IL-2 infusions, and all patients completed "maintenance." Postinfusion lymphocytosis was exhibited by patients at all IL-2 dose levels. With the higher IL-2 doses, increased percentages of patients' PBMC expressed CD16 and CD56, with augmented lysis of K562 and Daudi, reflecting the induction of natural killer and circulating LAK effector activities. Increased LAK precursor activity was exhibited by patients at all IL-2 dose levels. Thus, the IL-2 therapy regimen was safely tolerated after ABMT, and pronounced immunomodulatory effects were observed with the higher IL-2 doses. These studies support the planned use of IL-2 and LAK cells after ABMT in an attempt to reduce relapses of advanced hematologic malignancies.
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PMID:Toxicity and immunomodulatory effects of interleukin-2 after autologous bone marrow transplantation for hematologic malignancies. 204 62

A number of different combination regimens including high-dose corticosteroids (HDCS) have been widely used in an attempt to achieve better results for relapsed or alkylating agent-resistant multiple myeloma (MM). A major complication of these regimens is commonly said to be infection. In addition, we have had occasion to point out that a rapid progression of systemic amyloidosis can be one of serious complications of HDCS therapy in MM. The patient, born in 1940, was diagnosed of having Bence Jones (BJ) type MM in 1987. The conventional therapy including alkylating agents and interferon-alpha induced a partial remission of 22 months' duration. After the relapse, 2 courses of vincristine, adriamycin plus high-dose dexamethasone resulted in a reduction of the excreted amount of urinary BJ proteins with symptomatic improvement. However, the following clinical features indicating systemic amyloidosis occurred in succession within 2 months after beginning the therapy: submandibular swelling, giant tongue, shoulder pad sign, carpal tunnel syndrome, low voltage on ECG and recurrent diarrhea. The biopsy specimens from the submandibular gland revealed amyloid deposition. In the present case, a rapid progression of systemic amyloidosis is supposed to be attributable to the HDCS therapy. The possible mechanism of enhancement of amyloidosis by HDCS therapy is discussed.
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PMID:[Rapid progression of systemic amyloidosis after high-dose corticosteroid therapy in multiple myeloma]. 225 65

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

Lymph node cells from calves immunized with purified pilus antigen of K99+ enterotoxigenic E. coli (ETEC) were fused with mouse myeloma (NSO) cells, and with non-Ig producing mouse/calf hybridomas or with a bovine Ig-producing mouse/calf/calf secondary hybridoma. Lines secreting bovine monoclonal IgG1 specific for K99 pilus antigen in an ELISA were obtained in each case. The two lines derived from xenohybridoma fusion partners have been secreting anti-K99 bovine monoclonal antibody for over one year in continual passage. None of the antibodies cross-reacted with other pilus types including K88, CFAI, CFAII, 987P or CP; they all inhibited agglutination of horse RBC (which have a K99 receptor) in the presence of K99 antigen; they showed positive fluorescence in an indirect binding assay on K99+ ETEC and inhibited K99+ ETEC adhesion to piglet enterocytes. These antibodies have potential prophylactic and therapeutic use in control and treatment of diarrhoea.
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PMID:Bovine monoclonal antibodies to the F5 (K99) pilus antigen of E. coli, produced by murine/bovine hybridomas. 288 27

Cefbuperazone (CBPZ) was administered to patients with severe infections complicating hematologic diseases to assess its efficacy and safety under such clinical conditions. Primary diseases in this series of 78 cases included; acute leukemia in 41 cases, chronic leukemia in 6 cases, other leukemia in 9 cases, malignant lymphoma in 13 cases, multiple myeloma in 3 cases, aplastic anemia in 5 cases and 1 other case. Types of infection included sepsis; proven or suspected, in 59 cases, pulmonary infection in 8 cases, upper respiratory infection in 5 cases, and other cases. CBPZ was infused by an intravenous drip method at a dosage of 4-8 g daily. Patients' ages ranged from 14 to 85 years. Clinical response to the CBPZ regimen was excellent in 24 cases, good in 22 cases, fair in 2 cases, and poor in 30 cases. Thus the overall efficacy rate (percentage of cases showing an excellent or good response) was 59.0%. Efficacy rates for individual types of infection were: documented sepsis 16.7%, suspected sepsis 58.5%, lower respiratory infection 62.5%, and upper respiratory infection 100%. CBPZ also proved to be effective in 61.0% of cases with a neutrophil count of less than 500/mm3 prior to therapy. Side effects encountered were diarrhea in 1 case, gastric discomfort in 1 case and hepatic dysfunction in 5 cases. These side effects, however, were not dose-related, and none were serious. These results indicate that CBPZ has a high therapeutic efficacy even in patient with compromised immunodefenses.
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PMID:[Efficacy and safety of cefbuperazone in severe infections complicating hematologic diseases Hanshin Infection Study Group]. 304 32

We have reported the 21-year follow-up of a patient with progressive monoclonal IgG lambda gammopathy and recurrent pneumococcal infections who had diarrhea and weight loss. The serum IgG had risen from 2,850 mg/dl in 1966 to 6,120 mg/dl in 1986, but repeated evaluations had shown no evidence of myeloma or lymphoma. Evaluation revealed infiltration of the gastrointestinal tract by a plasmacytic malignancy with a surface heavy and light chain identical to her serum monoclonal band.
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PMID:Plasmacytic neoplasm of the gastrointestinal tract in a patient with long-standing monoclonal gammopathy. 317 43

Therapeutic effects on cefmenoxime hemihydrochloride (CMX, Bestcall), a new synthetic cephem antibiotic, were examined in the treatment of various infections complicated with hematological diseases. The number of patients treated with CMX was 37 including 5 cases of sepsis or suspected sepsis, 14 cases of pneumonia or suspected pneumonia, 5 cases of upper respiratory diseases, 2 cases of urinary tract infections and 11 cases of other infections. All of these infections were complicated with hematological diseases: Acute leukemia, 13 cases; chronic myelocytic leukemia, 1 case; adult T cell leukemia, 3 cases; malignant lymphoma, 8 cases; Hodgkin's disease, 2 cases and myeloma, 3 cases. CMX were administered by a single intravenous injection or by a drip infusion. The dose was between 2 and 6 grams per day. Good to excellent clinical results were obtained in 25 out of 37 cases, total effective rate of 67.6%. No clinical side effects or abnormal laboratory findings attributable to CMX were observed except for light diarrhea in 2 cases. By the clinical investigation, it was demonstrated that CMX was one of safe and effective antibiotics for treating infections in the compromised hosts complicated with hematological diseases.
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PMID:[Clinical investigation of the therapeutic effects of cefmenoxime in the treatment of infections complicated by hematological diseases]. 348 22

High dose melphalan (HDM, 140 mg/m2 i.v.) has been evaluated in 58 patients under 63 years with multiple myeloma. Among previously untreated patients 11/41 (27%) entered a complete remission (CR: no measurable myeloma protein and a normal bone marrow) and 21 (51%) entered a partial remission (more than 50% reduction in myeloma protein and improvement in all other features). Median duration of remission is 19 months. Two patients who had responded to previous conventional treatment entered CR after HDM. Among 15 patients who had failed on previous chemotherapy the response rate was 66% including two CRs. However, in this group all patients have relapsed within 1 year. Profound myelosuppression, moderate nausea, vomiting, mucositis and diarrhoea with reversible alopecia occurred in all patients. There were 10 deaths within 2 months of treatment mainly due to sepsis and haemorrhage. In a subsequent study, high dose methyl prednisolone (1 g/m2 daily for 5 d) has been added to HDM. Response rates are similar with 6/22 (27%) CR, 13/22 (59%) PR and 2/22 NR but there was only one early death, reflecting improvements in medical management. The high CR rate is an encouraging feature of this approach which is now to be the basis of a prospective trial sponsored by the Medical Research Council in which HDM, with and without steroids, is compared to the best available conventional therapy (the MRC VI Myelomatosis trial).
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PMID:Multiple myeloma treated with high dose intravenous melphalan. 359 57


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