Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HIV infection is commonly associated with cytopenias. The occurrence of erythrocytosis is rare, with only one report in the medical literature. We have described the case of an asymptomatic patient found to be seropositive for HIV. The blood counts were initially normal except for mild eosinophilia and thrombocytopenia. Over the next 18 months erythrocytosis developed and thrombocytopenia worsened. Workup at that time revealed elevated red cell mass, suppressed erythropoietin, normal arterial oxygen saturation, and splenomegaly documented by abdominal computed tomography. Zidovudine therapy was started in April 1990, when the CD4 cell count dropped below 500/mm3. Over the next 4 months the hematologic indexes returned to normal levels. The patient remains asymptomatic.
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PMID:Polycythemia as a complication of human immunodeficiency virus infection. 850 94

Rauscher murine leukemia virus induces an erythroleukemia in susceptible strains of mice that is associated with splenomegaly and viremia. This animal model has been used for evaluating the in vivo efficacy of potential anti-HIV agents. The in vivo antiviral activity of therapeutic agents has usually been determined by measuring a reduction in the spleen weights of compound-treated mice or by quantitating viremia with the UV-XC plaque assay. The UV-XC assay, however, is time-consuming and labor-intensive. Virions of Rauscher murine leukemia virus, like other retroviruses, contain the enzyme reverse transcriptase. Quantitating the level of this enzyme in infected mouse sera provides a more rapid measure of viremia in the animal. We have examined the effects of several reagents, including detergent, KCl, EGTA, dGMP, spermine, as well as protease and RNase inhibitors, on the reverse transcriptase assay. The optimized assay method was effective in evaluating the antiviral activity of AZT in the Rauscher murine leukemia virus in vivo model. The assay is also amenable to automation if large numbers of assays are required.
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PMID:Optimization of the reverse transcriptase assay for the detection of viral burden in mice infected with Rauscher murine leukemia virus. 891 Jun 49

A combination of antiretroviral drugs acting at different points in the virus replication cycle was evaluated in a murine retrovirus-induced immunodeficiency model of AIDS (MAIDS). Intramuscular administration of high doses of reduced glutathione (GSH, 100 mg/mouse/day) and AZT (0.25 mg/ml in drinking water) was found to reduce lymphoadenopathy (92%), splenomegaly (80%), and hypergammaglobulinemia (90%) significantly more than AZT alone. Combined treatment resulted in a reduction in proviral DNA content of 69, 66, and 60%, respectively, in lymph nodes, spleen, and bone marrow. Furthermore, the stimulation index of B cells was also significantly higher in animals receiving GSH and AZT whereas additional responses were not observed in the T cell stimulation index and blood lymphocyte phenotype analyses. In conclusion, the administration of high doses of GSH and AZT, a new combination of antiviral drugs, seems to provide additional advantages compared to single-agent therapy.
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PMID:Antiretroviral effect of combined zidovudine and reduced glutathione therapy in murine AIDS. 928 14

Anti-HIV-1 combination therapies, including protease and reverse transcriptase inhibitors, can reduce plasma viremia to undetectable levels within the first 2 weeks of treatment. This reduction is followed by a slower decline that primarily results from the presence of viral reservoirs such as CD4+ memory cells, dendritic cells, and macrophages. For this reason, we evaluated a new drug combination therapy that includes a lympholytic drug: (2-fluoro-ara-AMP, fludarabine) to eliminate cells already infected and an antiviral drug (azidothymidine [AZT]) to protect cells not yet infected. We used C57BL/6 mice infected with the retroviral complex LP-BM5, which developed severe immunodeficiency (i.e., murine AIDS), to select the most effective fludarabine regimen to inhibit disease progression, and then to evaluate the efficacy and toxicity of the fludarabine and AZT combinations. The results obtained show that intraperitoneal administration of fludarabine at 3 mg/mouse twice a day for 4 weeks is the most effective regimen in reducing splenomegaly, lymphadenopathy, hypergammaglobulinemia, and proviral DNA content in spleen and lymph nodes and in restoring the architecture of lymph nodes. Subsequently, we evaluated the combined or sequential administration of fludarabine and AZT. The data reported in this paper show that the sequential administration of the two drugs provides additive antiviral effects that reduce spleen and lymph node weights to normal values and proviral DNA content by approximately 95% in all infected organs; the phenotypes of blood T and B cells moved toward control values, although the number of B cells was significantly reduced by fludarabine treatment. Finally, we evaluated the outcome of the disease after suspension or continuation of different treatment regimens. In all treatment groups, the disease progressed and increased proviral DNA content was found in infected organs, but animals receiving the sequential administration of fludarabine and AZT were less affected than those receiving only fludarabine or the simultaneous administration of both. The results obtained suggest that fludarabine could be part of a new therapeutic approach aiming at eradicating HIV from those cells that have been already infected and that are not protected by highly active antiretroviral therapy (HAART).
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PMID:Inhibition of murine AIDS by alternate administration of azidothymidine and fludarabine monophosphate. 1083 56


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