Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The association of large granular lymphocyte leukemia (LGL-L) with hepatocellular carcinoma in a 55-year-old patient is described. An increased number of LGL was seen on peripheral blood smears. The immunophenotype was CD3+, CD4-, CD8+, and a study of the TCR gene rearrangement indicated the monoclonal nature of the proliferation. A liver mass was detected on CT scan and an ultrasound-guided fine needle biopsy revealed the presence of hepatocholangiocellular elements. A right hepatectomy was performed. Major neutropenia persisted despite corticosteroids and granulocyte colony-stimulating growth factor (G-CSF) therapy. Methotrexate at 20 mg/week failed to control lymphocytosis after three months of treatment. A new nodule of hepatocarcinoma reappeared twelve months after surgery and a liver resection was performed.
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PMID:Large granular lymphocyte leukemia associated with hepatocellular carcinoma: a case report. 864 51

Fludarabine phosphate selectively eliminates normal and malignant mononuclear cells in large animals and man through the inhibition of DNA synthesis. The drug depletes mononuclear cells from culture within 24 hours of initial exposure, CD4 and CD8 T cells being more sensitive than either CD20 B cells or CD34 bone marrow precursors. Mitogenic activation of lymphocytes enhances cellular elimination from culture. Fludarabine inhibits PHA-induced T-cell proliferation by >90 per cent and mixed lymphocyte reactions (allogeneic and xenogeneic) by >95 per cent. Fludarabine exerts its cytolytic effects through the induction of endonuclease-independent apoptosis. A 5-day course of fludarabine (50 mg/m2 intravenously once daily) induces both T- and B-cell lymphopenia in Cynomolgus monkeys and Papio baboons. Transient neutropenia was the only side-effect seen in experimental animals. Pretreatment of Cynomolgus monkeys with this regimen of fludarabine causes a prolongation of ABO-compatible skin allograft survival from 8 days (control) to 16 days (drug treated group). Secondary allotransplantation into presensitized recipients showed a similar prolongation of graft survival with fludarabine pretreatment (8 days vs 5 days control). Fludarabine promises to be a potent immunosuppressive agent with low clinical toxicity.
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PMID:Fludarabine phosphate: A DNA synthesis inhibitor with potent immunosuppressive activity and minimal clinical toxicity. 865 23

Felty syndrome, comprised of neutropenia, rheumatoid arthritis and splenomegaly, occurs in approximately 1% of patients with rheumatoid arthritis. Up to one third of these patients have an increased number of large granular lymphocytes. The usual immunophenotype of these cells is CD3+, CD8+, CD57+, T cell receptor (TCR) alpha beta. A patient with Felty syndrome and large granular lymphocytosis, who had an unusual immunophenotype CD3+, CD4-, CD8-, TCR gamma delta, is described. Her neutropenia responded to treatment with granulocyte colony stimulating factor (G-CSF), which was given in order to raise her neutrophil count prior to bilateral knee replacement surgery. Thus, Felty syndrome with large granular lymphocytosis is a heterogeneous condition, one in which TCR gamma delta large granular lymphocytosis may be found, and also shows a response to treatment with G-CSF.
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PMID:An unusual association of Felty syndrome and TCR gamma delta lymphocytosis. 865 18

The object of this case control study was to evaluate the frequency, the risk factors, the microbiological spectrum and the outcome of 249 cases of bacteraemia observed in 209 HIV-infected patients, most them affected by AIDS. The rate of bacteraemia in the total yearly HIV-related admissions increased from 4% in 1985 to 13% in 1993. The more common aetiological agents of bacteraemia were: Staphylococcus aureus (29.7%), non-typhoidal species of Salmonella (14.1%), Staphylococcus epidermidis (10.9%), Streptococcus pneumoniae (8.4%) and Pseudomonas aeruginosa (7.6%). A mixed flora was found in 14% of the episodes. Multivariate analysis of predisposing factors indicated that a low CD4+T-cell count (<0.2 x 10(9)/l) (P=0.01), use of central venous catheters (CVC) (P=0.01) and neutropenia (polymorphonuclear neutrophils <1.0 x 10(9)/l) (P=0.04) were independent risk factors for the development of bacteraemia. Logistic regression did not reveal any association of bacteraemia with intravenous drug abuse (on univariate analysis P=0.04). The response (31.8%). Recurrences to specific therapy was favourable in 170 episodes (68.2%); death occurred in 79 (31.8%). Recurrences arose in 40 patients, 17 (42.5%) of them died. The outcome of bacteraemia was influenced by a low number of CD4+T-cells (P<0.001) but not of polymorphonuclear cells. Our findings suggest that bacteraemia is a relatively common event in HIV-infected patients, especially under particular conditions (e.g. intravenous drug abuse, use of CVC, neutropenia and a low CD4-T-cell count). It requires special attention from physicians who must recognise and treat the condition promptly at an early stage.
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PMID:The impact of bacteraemia on HIV infection. Nine years experience in a large Italian university hospital. 866 42

Neutropenia occurs in approximately 17% of symptomatic patients infected with HIV. Results of studies have failed to demonstrate a consistent relationship between HIV-related neutropenia and the subsequent development of bacterial infections. This was a case control study to determine if HIV-related neutropenia was associated with increased rates of bacteremia. The experimental group was comprised of 29 patients infected with HIV that had an absolute neutrophil count less than 1000 cells/mm3 and were paired with 29 control subjects infected with HIV that had been matched for age, sex, CD4 count, and month and year of entry. The frequency of bacteremia was 12.6 per 100 patient months among the experimental group compared to a frequency of 0.87 per 100 patient months among the control group (relative risk [RR] = 14.9, P = 0.0027). Other independent risks for the development of bacteremia included central venous catheters (RR = 3.9, P = 0.03), with a trend toward increased risk for bacteremia in those patients who were intravenous drug users (RR = 3.8, P = 0.11), or who had infiltrative bone marrow disease (RR = 3.1, P = 0.11). Multivariate analysis demonstrated that neutropenia (odds ratio [OR] = 22.6, P = 0.028) and the presence of a central venous catheter (OR = 8.5, P = 0.026) were significant risks for bacteremia. These data suggest that neutropenia is a significant risk for the development of bacteremia in patients infected with HIV.
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PMID:Neutropenia is associated with bacteremia in patients infected with the human immunodeficiency virus. 878 77

Neutropenia complicates HIV disease or its treatment in a large proportion of patients. Hematopoietic growth factor support has been tested in a number of clinical settings in HIV disease and has been demonstrated to be of benefit for specific parameters. One consideration regarding the use of hematopoietic growth factors in HIV disease is their potential effect on HIV viral burden, since alterations in HIV expression have been documented with certain cytokines in vitro. It has also been reported that some cytokines, notably GM-CSF, potentiate the antiviral properties of thymidine analogs such as zidovudine (AZT) in vitro. We tested these observations in vivo. Twelve HIV-positive patients with a CD4 cell count < or = 200/mm3 or HIV plasma viremia who were receiving a stable dose of zidovudine were enrolled into three dose cohorts of yeast-derived GM-CSF at 50, 125, or 250 micrograms/m2 daily by subcutaneous self-injection for 28 days. Measurements of HIV activity included serum acid-dissociated HIV p24 antigen levels, plasma and peripheral blood mononuclear cell (PBMC) limiting dilution HIV culture, and plasma HIV quantitative competitive polymerase chain reaction (PCR). Serum and intracellular zidovudine levels were measured as well as hematologic, immunologic, and toxicity parameters. Virologic measures showed neither significant upregulation nor downregulation of serum acid-dissociated HIV p24 antigen, plasma and PBMC HIV culture, or PCR in association with GM-CSF administration. A trend toward increased intracellular AZT levels was noted, but this did not achieve statistical significance (p = 0.073). CD4 and CD8 lymphocytes were essentially unaffected while absolute neutrophil counts increased with GM-CSF administration as expected. These data suggest that administration of GM-CSF does not perturb HIV activity or immunologic parameters in patients receiving AZT for advanced HIV disease. No potentiation of AZT antiviral effect was demonstrated.
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PMID:Lack of in vivo effect of granulocyte-macrophage colony-stimulating factor on human immunodeficiency virus type 1. 884 19

Systemic non-Hodgkin's lymphoma and Kaposi's sarcoma occur in approximately 4% and 30% of patients with HIV infection, respectively. Single-agent or combination chemotherapy is often indicated for such patients. Combination chemotherapy produces a significant decrease in CD4 lymphocytes and significantly increases the risk of opportunistic infection. Supportive care should include prophylaxis against Pneumocystis carinii pneumonia and esophageal candidiasis. Herpes labialis frequently occurs, may be confused with chemotherapy-induced stomatitis, and it requires appropriate treatment and secondary prophylaxis once recognized. Antiretroviral therapy should be continued during chemotherapy, if possible, and should be selected based on the patient's prior antiretroviral exposure, the toxicity profile of the antiretroviral agent, the toxicity of the chemotherapy, and the potential for drug interaction. The use of hematopoietic growth factors as primary prophylaxis may be reasonable for patients at high risk for febrile neutropenia, although the information about their use in this population is limited.
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PMID:Infection prophylaxis and antiretroviral therapy in patients with HIV infection and malignancy. 891 6

We have previously reported that 3'-azido 3'-deoxythymidine (AZT) can possess a significant antineoplastic activity when combined with drugs that disrupt de novo thymidylate synthesis, such as 5-fluorouracil and methotrexate (MTX). The aim of the present study was to evaluate the efficacy and the tolerance of the combination AZT + MTX in human immunodeficiency virus (HIV)-related non-Hodgkin's lymphoma (NHL). Twenty-nine patients (22 men and 7 women), either newly diagnosed or pretreated, have been enrolled in the trial; the median age was 34 years, 45% had acquired immunodeficiency syndrome before lymphoma and 19 patients had less than 100 CD4 lymphocytes/microL. Histologic diagnoses were mainly Burkitt (27%) and diffuse large B-cell lymphoma (45%); extranodal involvement was present in 20 patients. The treatment plan included three weekly courses of MTX at 1 g/m2 (days 1, 8, and 15) plus oral AZT at 2 g/m2 (days 1, 2, and 3), 4 g/m2 (days 8, 9, and 10), and 6 g/m2 (days 15, 16, and 17), plus leucovorin rescue. From the eleventh patient on, in case of complete or partial remission, the treatment was continued with three additional courses, using AZT at the maximum dose. In 26 evaluable patients, the total (complete + partial) response rate was 77% (95% confidence interval, 58% to 89%), with complete remission (CR) in 46% of the patients (95% confidence interval, 29% to 65%). The median CR duration was 12.8 months. Grade III-IV neutropenia and anemia were observed in 52% and 31% of the courses, respectively. There was one therapy-related death due to bacteremia followed by septic shock; the only other recorded infection was a herpes vaginalis. In conclusion, we suggest that AZT + MTX is an effective and well-tolerated regimen in HIV-related NHL.
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PMID:3'-Azido 3'-deoxythymidine + methotrexate as a novel antineoplastic combination in the treatment of human immunodeficiency virus-related non-Hodgkin's lymphomas. 900 43

Granulocyte-colony stimulating factor (G-CSF) is known to induce proliferation and differentiation of granulocyte progenitors, and is widely used to treat neutropenia induced by intensive chemotherapy for malignant lymphoma or adult T-cell leukaemia/lymphoma (ATL). G-CSF is thought not to stimulate malignant lymphoid cells. In the present study we examined the ability of G-CSF to induce in vitro growth of primary ATL cells from 14 patients (nine acute-type, two chronic-type and three lymphoma-type), and we analysed the in vivo counts of ATL cells in patients who received G-CSF for neutropenia. FACS analysis using phycoerythrin-labelled recombinant G-CSF demonstrated that ATL cells from 11/14 patients express some G-CSF receptor (G-CSFR), with a range between 5.4% and 87.3%. Cells expressing G-CSFR also expressed CD4. Reverse polymerase chain reaction (PCR) analysis demonstrated expression of G-CSFR messenger RNA in G-CSFR expressing cells. Leukaemic cells derived from seven (four acute-type, one chronic-type and two lymphoma-type) of the 14 patients proliferated in vitro in response to G-CSF, as measured by [3H]thymidine incorporation; maximum responses were at G-CSF concentrations of 10-100 ng/ml. Nine of 14 patients receiving rG-CSF for neutropenia were analysed retrospectively for ATL cell numbers. Four patients whose primary tumour cells proliferated in response to rG-CSF in vitro showed a significant increase in ATL cell count after administration of rG-CSF (P = 0.038), whereas five patients whose leukaemic cells did not proliferate in vitro showed no significant increase in ATL cell count. G-CSF can stimulate proliferation of ATL cells which may complicate therapy for this disease.
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PMID:Granulocyte-colony stimulating factor-induced proliferation of primary adult T-cell leukaemia cells. 907 11

Thrombocytopenia in persons infected with HIV is prevalent and has numerous causes. To study the occurrence, associations, and effect on survival of thrombocytopenia in HIV-infected persons, we used surveillance data from a longitudinal survey of the medical records of 30,214 HIV-infected patients who received medical care from January 1990 through August 1996 in more than 100 medical clinics in 10 U.S. cities. Thrombocytopenia was defined as a physician diagnosis of thrombocytopenia or a platelet count of < 50,000 platelets/ microliter. Analysis of associations of thrombocytopenia was conducted using logistic regression. In HIV+ patients, the 1-year incidence [corrected] of thrombocytopenia was 8.7% in persons with one or more AIDS-defining opportunistic illnesses (clinical AIDS), 3.1% in patients with a CD4 count < 200 cells/mm3 but not clinical AIDS (immunologic AIDS), and 1.7% in persons without clinical or immunologic AIDS. The incidence of thrombocytopenia was associated with clinical AIDS (adjusted odds ratio [AOR] 2.2; 99% confidence interval [CI] 1.7-3.0), immunologic AIDS (AOR 1.5, CI 1.0-2.1), history of injecting drug use (AOR 1.4, CI 1.0-1.9), anemia (AOR 5.0, CI 3.8-6.7), lymphoma (AOR 3.7, CI 1.3-10.6), and black race (AOR 0.7, CI 0.5-0.9). After controlling for anemia, clinical AIDS, CD4 count, neutropenia, antiretroviral therapy, and Pneumocystis carinii pneumonia prophylaxis, thrombocytopenia was significantly associated with decreased survival (risk ratio 1.7; 95% CI, 1.6-1.8). Thrombocytopenia in HIV-infected persons is an important clinical condition associated with shorter survival.
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PMID:Surveillance for thrombocytopenia in persons infected with HIV: results from the multistate Adult and Adolescent Spectrum of Disease Project. 911 81


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