Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tiazofurin, an investigational antimetabolite, is undergoing clinical evaluation in leukemia. We analyzed the data base of 198 patients entered in Phase I trials to characterize the incidence and severity of toxicities associated with tiazofurin according to dose and schedule. Severe myelosuppression occurred infrequently, and was not dose-dependent. A five day bolus schedule had a higher incidence of severe or life-threatening neutropenia than other schedules. Tiazofurin produced lymphopenia which was not dose-dependent in the range of 23-36% decrease from baseline, and the effect on lymphocyte count was generally greater than the decline in neutrophil count. Non-hematologic toxicity of a moderate or worse severity (greater than or equal to grade 2) included nausea and vomiting (18% of all courses), serum transaminase elevations (SGOT, 16%; SGPT, 9%), rash (9%), stomatitis (3%), conjunctivitis (3%), headache (10%), other signs of central nervous system toxicity (8%), and cardiac toxicity, primarily pleuropericarditis (4%). Dose-related cutaneous toxicity, headache, and nausea and vomiting were evident in the five day bolus schedule, and myalgia was more frequently reported at higher doses on the single dose schedule. The five day continuous infusion (CI) schedule had a higher incidence of neurotoxicity, cardiac toxicity, SGPT elevations and ocular toxicity than the daily for five days bolus schedule, but none of these differences attained statistical significance. Although the peak plasma concentrations of tiazofurin achieved with the five day bolus schedule were 3-fold higher than the steady-state plasma levels seen with an equal dose given by CI, the area under the concentration-time curve (AUC) was approximately 1.6-fold higher with CI. These observations suggest that both high peak plasma concentrations (above 400 microM) and prolonged exposure to plasma levels exceeding 50 microM may result in a higher incidence of serious non-hematologic toxicity.
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PMID:Clinical toxicity associated with tiazofurin. 220 Jul 59

Studies were done on 53 cats with community-acquired infection with the feline immunodeficiency virus (FIV) to determine if hematologic abnormalities were comparable with those observed in patients seropositive for the human immunodeficiency virus (HIV). Nine cats were asymptomatic, 24 had clinical symptoms equivalent to AIDS-related complex (ARC), and 20 had AIDS-like disease. Hematologic abnormalities were detected in 75% (40 of 53) of FIV-seropositive cats, and multiple concurrent cytopenias were common. Anemia, lymphopenia, neutropenia, and thrombocytopenia occurred in 36%, 53%, 34%, and 8% of FIV-seropositive cats, respectively. Cytopenias were seen only in symptomatic (ARC or AIDS) cats. The occurrence of cytopenias and the distribution of clinical stages were similar in cats with concurrent feline leukemia virus (FeLV) infection and those with FIV alone, suggesting that these abnormalities were a direct consequence of FIV infection. In addition, abnormalities were noted in 72% of marrows from symptomatic cats and included hyperplasia of individual cell lineages and dysmorphic features. Our results demonstrate that the hematologic manifestations of FIV infection are strikingly similar to those reported in HIV-seropositive patients. Thus, FIV infection in cats is an excellent animal model to study the pathogenesis of blood and marrow abnormalities in AIDS, as well as to evaluate the hematologic toxicities of drug therapies.
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PMID:Hematologic manifestations of feline immunodeficiency virus infection. 240 Aug 6

Severe progressive immunodeficiency syndrome can be induced experimentally with a molecularly cloned isolate of feline leukemia virus (FeLV-FAIDS). The resultant disease syndrome is characterized by persistent viremia, lymphopenia, progressive weight loss, persistent diarrhea, enteropathy, and opportunistic infections. The onset of clinical immunodeficiency disease is prefigured by the replication of the FeLV-FAIDS variant virus in bone marrow and other tissues. The FeLV-FAIDS system can be used to evaluate antiviral agents which act on steps in the replication cycle which are conserved among retroviruses (e.g. reverse transcriptase, protease, assembly). The persistence and magnitude of viremia serves as a useful parameter in antiviral studies because it can be easily measured, presages the eventual development of immunodeficiency, and provides a convenient indicator of therapeutic efficacy either in preventing de novo FeLV infection or in reversing or ameliorating established infection. We describe here the evaluation of 2',3'-dideoxycytidine (ddC) against FeLV-FAIDS infection - both in vitro in cell culture assay systems and in vivo in cats administered ddC either via intravenous bolus dosage or via controlled release subcutaneous implants. We found that, although controlled release delivery of ddC inhibited de novo FeLV-FAIDS replication and delayed onset of viremia when therapy was discontinued (after 3 weeks), an equivalent incidence and level of viremia were established rapidly in both ddC-treated and control cats. The FeLV model, therefore, can be used to assess rapidly experimental single agent or combined antiviral therapies for persistent retrovirus infection and disease.
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PMID:Feline leukemia virus-induced immunodeficiency syndrome in cats as a model for evaluation of antiretroviral therapy. 254 Jan 9

Diethylcarbamazine (N,N-diethyl-4-methyl-1-piperazine carboxamide [DEC]) is widely used, especially in tropical regions, to prevent and treat filariasis. The antifilarial effect of this drug has been attributed to immunomodulation. Evidence is accumulating to indicate that DEC may mitigate the course of feline leukemia virus infection (FeLV) in cats. Previous studies have suggested that continuous oral DEC treatment given shortly after evidence of FeLV infection prevents or delays lymphopenia and prolongs survival. The present study focuses on the hematologic effects of one month oral DEC treatment given to adult chronically FeLV-infected cats and uninfected cats as compared to untreated FeLV-infected cats. Such treatment frequently resulted in abruptly lowered peripheral lymphocyte counts in chronically FeLV-infected cats. Further studies are warranted to evaluate whether administration of DEC could eliminate circulating retroviral-infected cells.
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PMID:Hematologic effects of short-term oral diethylcarbamazine treatment given to chronically feline leukemia virus-infected cats. 254 97

Compliance with chemotherapy in childhood leukaemia is usually good because of parental fear of the disease. However, poor compliance and refusal of treatment have been reported from both the USA and the UK. Little is known about African concepts of leukaemia, attitudes to treatment or compliance. A study was undertaken to investigate factors which might affect compliance in 15 black and 30 white families of leukaemic children in Johannesburg. The socio-economic and educational status of the black families was lower than that of the white. Only 53% of black children attended hospital on the appointed day compared with 90% of white children. Less than 50% of black parents understood the nature of their child's illness. Both black and white families had unused medication at home. White parents more frequently reported toxic effects related to chemotherapy and more white children than black children exhibited lymphopenia during maintenance therapy. Assessment of drug compliance should be included as an independent variable when evaluating factors affecting response to chemotherapy in communities of diverse ethnic, socio-economic and cultural backgrounds.
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PMID:Compliance with chemotherapy in childhood leukaemia in Africa. 272 28

BALB/c mice infected with ts1, a mutant of Moloney murine leukemia virus-TB, develop generalized body wasting, profound neurologic disorders, severe thymic atrophy and lymphopenia due to destruction of T lymphocytes and drastic immunodeficiency. ts1 was found not only able to infect T lymphocytes but also to impair their function. In addition, ts1 also infects and induces syncyntia formation in macrophages. The genetic determinant(s) responsible for ts1's ability to induce immunodeficiency has been localized to the env gene.
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PMID:ts1, a mutant of Moloney murine leukemia virus-TB, causes both immunodeficiency and neurologic disorders in BALB/c mice. 272 46

CBA/Ca male mice have been exposed to benzene in air at 10, 25, 100, 300, 400, and 3000 ppm for variable intervals 6 hr/day, 5 days/week for up to 16 weeks. Two weeks of inhaling 10 ppm produced no hematologic effects; 25 ppm induced a significant lymphopenia. Inhalation of 100, 300, and 400 ppm produced dose-dependent decreases in blood lymphocytes, bone marrow cellularity, marrow content of spleen colony-forming units (CFU-S) and an increased fraction of CFU-S in DNA synthesis. Exposure of mice to 300 ppm for 2, 4, 8, and 16 weeks produced severe lymphopenia and decrease in marrow CFU-S. Recovery was rapid and complete after 2 and 4 weeks of exposure. After 8 and 16 weeks of exposure, recovery of lymphocytes was complete within 8 weeks. It took 16 weeks for the CFU-S to recover to that of the age-matched controls after 8 weeks of exposure and 25 weeks to recover to age-matched after 16 weeks of exposure. Inhalation of 3000 ppm for 8 days was less damaging than inhalation of 300 ppm for 80 days (same integral amount of benzene inhaled). The inhalation of 3000 ppm has not increased the incidence of leukemia or shortened its latency for development. Inhalation of 300 ppm 6 hr/day for 16 weeks significantly increases the incidence of myelogenous neoplasms in male CBA/Ca mice. Inhalation of 100 ppm for same interval does not influence incidence of myelogenous neoplasms but does increase incidence of solid neoplasms particularly in female CBA/Ca mice. Benzene is a potent carcinogen in CBA/Ca mice.
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PMID:Hematotoxicity and carcinogenicity of inhaled benzene. 279 54

We describe the identification, experimental transmission, and pathogenesis of a naturally occurring powerfully immunosuppressive isolate of feline leukemia virus (designated here as FeLV-FAIDS) which induces fatal acquired immunodeficiency syndrome (AIDS) in 100% (25 of 25) of persistently viremic experimentally infected specific pathogen-free (SPF) cats after predictable survival periods ranging from less than 3 months (acute immunodeficiency syndrome) to greater than one year (chronic immunodeficiency syndrome), depending on the age of the cat at time of virus exposure. The pathogenesis of FeLV-FAIDS-induced feline immunodeficiency disease is characterized by: a prodromal period of largely asymptomatic viremia; progressive weight loss, lymphoid hyperplasia associated with viral replication in lymphoid follicles, lymphoid depletion associated with extinction of viral replication in lymphoid follicles, intractable diarrhea associated with necrosis of intestinal crypt epithelium, lymphopenia, suppressed lymphocyte blastogenesis, impaired cutaneous allograft rejection, hypogammaglobulinemia, and opportunistic infections such as bacterial respiratory disease and necrotizing stomatitis. The clinical onset of immunodeficiency syndrome correlates with the replication of a specific FeLV-FAIDS viral variant, detected principally as unintegrated viral DNA, in bone marrow, lymphoid tissues, and intestine. Two of seven cats with chronic immunodeficiency disease that survived greater than 1 year after inoculation developed lymphoma affecting the marrow, intestine, spleen, and mesenteric nodes. Experimentally induced feline immunodeficiency syndrome, therefore, is a rapid and consistent in vivo model for prospective studies of the viral genetic determinants, pathogenesis, prevention, and therapy of retrovirus-induced immunodeficiency disease.
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PMID:Experimental transmission and pathogenesis of immunodeficiency syndrome in cats. 282 40

Cats exposed to the feline leukemia virus (FeLV) may mount an effective immune response and eliminate the virus, develop a non-viremic, latent infection or become persistently infected and shed the virus. Persistently infected cats commonly die of secondary opportunistic infections that result from FeLV-induced immunosuppression. The acquired immunosuppression is the most frequent and most devastating consequence of FeLV infection in the cat. Immunosuppression is targeted primarily to the cell-mediated immune system and has been attributed to the viral p15e envelope protein. The decreased IgG response and proliferative response to T cell mitogens is thought to be due to a defect in the helper cell function. As a result of T helper cell immunosuppression, infected cats may also have defective cytotoxic lymphocyte and activated macrophage functions which are regulated by their lymphokines. Research has shown that the virus causes a general suppression in the production of T cell-derived lymphokines, including gamma interferon and interleukin 2. A decrease in the function of polymorphonuclear leukocytes has also been reported and may contribute to deaths due to opportunistic infections in FeLV-positive cats. There are numerous parallels between the acquired immunodeficiency syndrome (AIDS) in man and the FeLV-induced immunodeficiency syndrome in cats. Frequent deaths due to opportunistic infections, lymphopenia, depressed cell-mediated immune responses to T cell-dependent antigens despite hypergammaglobulinemia and the presence of a long period of time between infection and the onset of clinical signs are just a few of the syndromes that are similar between the 2 retroviral diseases. A new strain of FeLV, FeLV-FAIDS has been associated with a naturally occurring immunosuppressive syndrome that is strikingly similar to AIDS in man. In addition, a T-lymphotropic retrovirus has recently been identified from cats with an immunodeficiency-like syndrome; this feline lentivirus disease is morphologically similar, but antigenically distinct from the human immunodeficiency virus, the cause of AIDS. Treatment for FeLV immunosuppression is primarily supportive. The development of a soluble tumor cell antigen vaccine has been shown to be efficacious in preventing FeLV infections.
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PMID:Clinical and immunologic aspects of FeLV-induced immunosuppression. 284 93

In previous studies, administration of diethylcarbamazine (DEC) resulted in increased serum antibody titers to feline oncornavirus-associated cell membrane antigen (FOCMA) in cats infected with feline leukemia virus (FeLV). FeLV infection of cats frequently results in immunosuppression associated with lymphopenia. The present investigation demonstrated that chronic administration of DEC prevented or delayed severe lymphopenia in two FeLV-infected offspring of an FeLV-infected queen as compared to two untreated littermates.
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PMID:Effect of continuous oral diethylcarbamazine treatment on lymphocyte counts of feline leukemia virus-infected cats. 285 80


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