Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Of the many varieties of drug interactions, which occur when the disposition or actions of one drug are changed by another, only a few are serious or potentially fatal. A representative outline of some of these illustrates the problem. Precipitant drugs are those which produce the interaction, and object drugs are those whose effects are changed. The interactions which are usually significant are those which alter the metabolism, involve renal excretion, or change the effects of the object drug, especially when the object drug has a low therapeutic index (cardiovascular drugs, anticoagulants, drugs acting on the brain, hypoglycemic drugs, hormones, and cytotoxic drugs). Warfarin toxicity, for example, is produced by aspirin, phenylbutazone, and azapropazone. The dosage requirements of warfarin are reduced by chloramphenicol, ciprofloxacin and other quinolones, erythromycin and some of the other macrolides, metronidazole and other imidazoles, tetracyclines, amiodarone, cimetidine (but not ranitidine), and fibrates. Potassium-depleting drugs can potentiate the action of digoxin, and the elimination of digoxin can be reduced by amiodarone, propafenone, quinidine, and verapamil. Combined oral contraceptives can lose effectiveness through the interaction of carbamazepine, griseofulvin, phenytoin, or rifampicin, which increase estrogen metabolism. In addition, broad-spectrum antibiotics such as ampicillin or tetracyclines also reduce contraceptive effectiveness by altering gut absorption. Even a single drink of an alcoholic beverage may be dangerous to people taking antidepressants, antihistamines, antipsychotic drugs, benzodiazepines, or lithium. Antihistamines suffer inhibited metabolism in the liver if taken in conjunction with the antifungal imidazoles and some of the macrolide antibiotics. Cardiotoxicity of antihistamines is also enhanced by drugs with similar cardiotoxic effects. Lithium potentiation is enhanced by the new serotonin-reuptake inhibitors, and lithium excretion can be reduced by diuretics or fluoxetine. When drugs such as antifungal imidazoles, azapropazone, or phenylbutazone are permitted to inhibit the metabolism of sulphonylureas, hypoglycemic effects are enhanced and, if unnoticed, may cause brain damage. Fibrates should not be combined with HMG-CoA reductase inhibitors because of the increased risk of myopathy. Patients taking non-selective monoamine oxidase inhibitors should avoid amine-containing foods and drugs such as matured cheeses, meat, yeast extracts, some wines, unfresh protein, and cold-curing medications. The metabolism of azathioprine is inhibited by allopurinol, and this combination requires a reduced dosage of azathioprine. Mercaptopurine, used in the treatment of leukemia, is also a metabolite of azathioprine. Sources of comprehensive information on drug interactions are 1) the "British National Formulary," appendix 1; 2) Chapter 10 of "The Oxford Textbook of Clinical Pharmacology and Drug Therapy"; and 3) a monograph by Stockley entitled "Drug Interactions."
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PMID:Serious drug interactions. 790 48

The dissemination pattern of a human non-Hodgkin's lymphoma (NHL) B cell line (DoHH2) carrying the t(14;18) translocation was analyzed in severe combined immunodeficient (SCID) mice, using different routes of administration. When engrafted intraperitoneally (i.p.) the DoHH2 cells showed a local infiltration into intra- and retroperitoneal mouse tissues, and disseminated to bone marrow and lymph nodes. In contrast, after subcutaneous (s.c.) or intravenous (i.v.) transfer the DoHH2 cells displayed a hematogenous spread, and disseminated predominantly to hematopoietic and lymphoid organs including bone marrow, peripheral blood, spleen, peripheral lymph nodes, and liver. No involvement of the gut and mesenteric lymph nodes was observed, suggesting a specific homing pattern, bypassing the mucosa-associated lymphoid tissue (MALT). This pattern is reminiscent of the human disease. Phenotypic analysis, cytogenetic analysis, and minor histocompatibility antigen (mHA) typing using mHA-specific cytotoxic T-lymphocyte (CTL) clones performed on the original DoHH2 cell line and on DoHH2 cells recovered from mouse tissue, showed that in vivo passage did not alter the characteristics of the DoHH2 cells. After i.v. administration, the survival time of the SCID mice directly correlated with the number of DoHH2 cells inoculated. This model of dissemination of the DoHH2 cell line may be useful for studying the efficacy of (immunotherapeutic) treatment of human lymphoproliferative disorders in vivo.
Leukemia 1994 Aug
PMID:Homing and antigenic characterization of a human non-Hodgkin's lymphoma B cell line in severe combined immunodeficient (SCID) mice. 805 78

A murine acquired immunodeficiency syndrome (MAIDS) is induced in genetically susceptible strains of mice inoculated with LP-BM5 murine leukemia virus. It is characterized by progressive lymphoproliferation, profound immunodeficiency, and the subsequent loss of resistance to opportunistic pathogens, including intestinal pathogens. Cellular and/or humoral immunity of gut-associated lymphoid tissues may play a key role in the elimination of these pathogens. We have previously demonstrated reductions in the number of mucosal T and B cells in MAIDS. In this study, the cytokine production by mesenteric lymph nodes (MLN) cells and their proliferative response to mitogens during MAIDS were investigated. Alterations were observed in the kinetics of MLN cell proliferation and cytokine secretion by in vitro mitogen-stimulated MLN cells during the retrovirus infection. Cytokine production was abnormally changed, with a gradual decrease in interleukin-2 (IL-2) production as well as an increase in IL-5 and IL-6 secretion. Interferon-gamma production was increased during the progression to MAIDS. The dysregulated release of cytokines by MLN cells due to retrovirus infection could lead to immune dysfunction. These data indicate that dysregulated cytokine secretion by MLN cells may be responsible for impaired mucosal immunity in AIDS, explaining the dramatic increase of opportunistic intestinal pathogens in individuals with AIDS.
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PMID:The kinetics of cytokine secretion and proliferation by mesenteric lymph node cells during the progression to murine AIDS, caused by LP-BM5 murine leukemia virus infection. 806 35

The pattern of remission deaths was examined in 842 children with acute lymphoblastic leukaemia (ALL) treated at a single centre over 18 years. The mortality rate from leukaemia fell significantly during three consecutive time periods during which treatment became progressively more intensive and that during remission induction fell from 3.5% to under 1%, but the rate of death in remission stayed constant at 5-6%. The factors associated with an increased risk of remission death were: young age, a higher leucocyte count, bone marrow transplantation, and Down's syndrome. The pattern of remission deaths changed over the years; measles and herpes viruses decreased while deaths associated with periods of intensification and gut toxicity increased. Four children developed second neoplasms. Treatment of ALL is still associated with a significant risk of death in remission but the pattern of infective deaths has changed. Many should be avoidable by provision of adequate supportive care, close supervision after periods of intensive treatment, and appropriate antibiotic, antifungal, and cytokine therapy.
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PMID:Remission death in acute lymphoblastic leukaemia: a changing pattern. 825 73

A 3-year old child with juvenile chronic myeloid leukaemia received a T cell-depleted BMT from a male unrelated donor. There was early graft failure associated with increasing splenomegaly and hypersplenism. Splenectomy was performed 53 days post-transplant and was followed by autologous marrow recovery with return of leukaemia. A second unrelated donor BMT was performed 9 months later using T cell-replete marrow from a similarly matched female donor. Grade 2 GVHD involving the skin and gut responded to treatment with steroids. Chimaerism was assessed using Y-specific polymerase chain reaction (PCR) and microsatellites. Samples taken at the time of splenectomy showed no donor marrow engraftment but there was significant engraftment in the spleen. Following the second transplant, donor-type haematopoiesis was documented using a panel of microsatellite probes. The patient remains well 6 months after transplant. Splenectomy should be considered prior to transplant in patients with significant splenomegaly and hypersplenism. Partial chimaerism in the spleen, but not bone marrow, post-BMT, has not previously been documented. PCR technology is a useful and highly sensitive way to assess chimaerism post-BMT and is informative in sex-matched cases, whilst the small amount of material required is advantageous in paediatric patients.
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PMID:Successful second unrelated donor BMT in a child with juvenile chronic myeloid leukaemia: documentation of chimaerism using the polymerase chain reaction. 843 16

A 16-year-old white male with acute biphenotypic leukemia developed evidence of the eosinophilia myalgia syndrome associated with total parenteral nutritional support with solutions containing tryptophan, which were given during his initial induction chemotherapy and also after autologous marrow transplantation. He developed pronounced eosinophilia and a vasculitic skin rash, myalgias of the abdomen, upper trunk, and neck, and died of respiratory distress with no evidence of an infectious etiology. Autopsy revealed diffuse vasculitis involving the heart, lungs, kidneys, testes, spleen, liver, skin, gut wall and marrow with neuritis of gut wall nerves and ganglia. Thus, the eosinophilia myalgia syndrome can be associated with parenteral tryptophan administration.
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PMID:Fatal eosinophilia myalgia syndrome in a marrow transplant patient attributed to total parenteral nutrition with a solution containing tryptophan. 843 65

A 15 year old boy being treated for relapsed acute lymphoblastic leukaemia developed severe diarrhoea and abdominal pain which worsened despite empirical antibiotic treatment. A right hemicolectomy was performed. The caecum and ascending colon showed changes typical of neutropenic enterocolitis. Clostridium tertium was isolated from faeces, blood cultures, and from the resected gut wall, with no evidence of other organisms capable of causing such a condition. As far as is known, this is the first reported case in which neutropenic enterocolitis has been associated with well documented C tertium infection, an organism previously described as a cause of bacteraemia in neutropenic patients.
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PMID:Neutropenic enterocolitis associated with Clostridium tertium. 845 41

Using multivariate techniques, we studied the relationships of cytotoxic regimen, intestinal mucosal damage, and fungal colonization in the pathogenesis of invasive fungal disease in 138 patients undergoing induction therapy for untreated acute myeloid leukemia (AML) according to three institutional protocols: AML-84 (cytarabine/daunorubicin), AML-87 (high-dose cytarabine/etoposide/daunorubicin), and AML-88 (mitoxantrone/etoposide). Invasive fungal disease occurred in 36%, 6%, and 2.6% of patients participating in protocols AML-87, AML-84, and AML-88, respectively (chi 2 = 23.465; P < .0001). Protocol AML-87 was the strongest independent predictor in the multivariate model (RR = 26.7; P < .0001). Cytotoxic therapy-related epithelial damage in the gut, as measured by D-xylose malabsorption, correlated with invasive fungal disease and protocol AML-87. Fungal colonization, a predictor of invasive fungal disease, correlated with frequent modifications of antibiotic regimens. These results demonstrate the role of cytotoxic regimen-related gut epithelial damage, antibiotic-prescribing behavior, and fungal colonization in the pathogenesis of invasive fungal disease in patients with leukemia.
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PMID:Invasive fungal disease in adults undergoing remission-induction therapy for acute myeloid leukemia: the pathogenetic role of the antileukemic regimen. 856 45

Interleukin 11 (IL-11) is a stromal cell-derived cytokine that has multiple effects on hematopoietic and nonhematopoietic systems. In vitro, it enhances the growth of early progenitors and promotes megakaryocytopoiesis and erythropoiesis. In healthy animals, IL-11 administration stimulates megakaryocyte maturation and increases peripheral platelet counts. IL-11 accelerates the recovery of peripheral neutrophil, erythrocyte, and platelet counts in mice that have undergone cytoablative treatment. Therefore, IL-11 may be useful clinically as an agent promoting recovery from hematopoiesis. However, its clinical use in patients with hematological malignancies may be restricted because IL-11 has been reported to stimulate some leukemia and myeloma cells. In the United States, phase I trials have shown that IL-11 accelerates recovery from chemotherapy-induced or bone-marrow transplantation (BMT)-induced thrombocytopenia. In Japan, phase II trials studying the thrombopoietic effect of IL-11 in patients with solid tumors postchemotherapy, in patients undergoing BMT, and in patients with aplastic or refractory anemia are now under way. Recently, thrombopoietin (TPO) has been cloned, and its thrombopoietic effect and accelerating effect on platelet count recovery in thrombopoietic states have been demonstrated in animal models. The physiological effect of TPO is restricted to hematopoiesis; therefore, it may have fewer side effects than IL-11. However, in addition to its hematopoietic effect, IL-11 administration to mice that have undergone cytoablative therapy significantly decreases morbidity and mortality due to chemotherapy-related endogenous infections caused by gut microorganisms. Therefore, IL-11 can be used in patients postchemotherapy and post-BMT not only to promote platelet recovery but also to prevent life-threatening infections. The use of in-vitro-expanded hematopoietic stem cells for BMT or as target cells for gene therapy is one of the most exciting areas in the field of medicine. Since IL-11 can expand hematopoietic progenitor-cell populations when used in combination with other cytokines, it may be useful as an ex vivo hematopoietic progenitor-cell-amplifying agent.
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PMID:Effect of interleukin 11 on normal and pathological thrombopoiesis. 876 27

The cholecystokinin (CCK)-B/gastrin receptor binds two brain-gut hormones, CCK and gastrin, with high affinities. These peptides have a trophic effect on gastrointestinal cells expressing the receptor in vivo as well as in vitro. Recently, this receptor mRNA was reported to be expressed in immunocytes localized in the lamina propria of normal rat stomach mucosa. Here, we studied the receptor expression in human hematopoietic cells in order to determine whether they play a role in cell growth. The CCK-B/gastrin receptor mRNA was detectable in the polymorphonuclear (PMN) cells but not in the mononuclear cells of normal peripheral white blood cells by reverse transcription-polymerase chain reaction. The receptor transcript was, however, expressed in human leukemia cell lines (14 of 18 cell lines tested) derived from not only myeloid, but also T- and B- lymphoid lineages. The CCK-B/gastrin receptors on several leukemia cell lines were shown to be biologically active by demonstrating ligand-dependent cell proliferation in serum-deprived medium. Interestingly, a human CCK-B/gastrin receptor specific antagonist, YM022, but not its stereotype isoform, selectively inhibited the DNA synthesis of THP-1, MOLT-16, MOLT-14, and CCRF-CEM in the absence of exogenous peptide ligands. Further investigation revealed that these leukemia cell lines and normal PMN cells also expressed gastrin mRNA. These results suggest that growth of human leukemia cells is promoted by an autocrine mechanism through the CCK-B/gastrin receptors.
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PMID:Autocrine loop through cholecystokinin-B/gastrin receptors involved in growth of human leukemia cells. 883 63


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