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)

Recombinant bovine interferon-alpha I1 (rBoIFN-alpha) has known antiviral and immunomodulatory effects which have been exploited to reduce clinical disease in a number of clinical situations including bovine respiratory diseases. A slow release rBoIFN-alpha formulation may be of value to reduce bovine respiratory disease under field conditions by extending the period of protection, and hence improving the prophylactic benefits of rBoIFN-alpha. In this report, we describe a formulation of rBoIFN-alpha in sesame oil containing calcium stearate which can successfully sustain the release of rBoIFN-alpha over an 8-day period. Recombinant bovine IFN-alpha could be measured in serum for 8 days following treatment with an initial burst of release 6 h after injection. After a single subcutaneous depot injection of 50 mg and 100 mg of rBoIFN-alpha, initial serum levels reached 12-15 ng/ml and 25 ng/ml respectively. Correlating with this burst of release, there was a decrease in the number of circulating CD4-CD8- gamma delta+ T lymphocytes, and a slight neutropenia. No alterations in other cell phenotypes tested (CD4, CD8, CD2, CD6, B cells, monocytes or MHC class II) were observed, nor were there changes in lymphokine activated killer (LAK), natural killer (NK) cell activity, or oxygen radical formation (assessed by reduction of nitroblue tetrazolium). However, despite the rapid and short-lived burst of rBoIFN-alpha, levels of 2-5 oligoadenylate (2-5 A) synthetase remained elevated for 8 days. The sustained increase of 2-5 A synthetase was not due to the high initial dose released during the burst 6-12 h after injection, since injection of a bioavailable equivalent dose of interferon induced a significant rise in 2-5 A synthetase activity for 4 days only. As 2-5 A synthetase is known to be a correlate of antiviral activity, we propose that this formulation of rBoIFN-alpha may be one approach to increase the window of protection, leading to more effective prevention of bovine respiratory disease.
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PMID:A slow release formulation for recombinant bovine interferon alpha I-1. 814 91

Neither single-agent therapy nor any combination treatment has been satisfactory enough to be regarded as standard in systemic advanced Kaposi sarcoma. In an attempt to achieve high efficacy in combination with low toxicity, we used a new liposomal formulation of doxorubicin. Pharmacologic data had established a long plasma half-life, an increased accumulation in tumor tissue, and a decrease in uptake by tissues such as liver, spleen, and bone marrow. In a phase I/II open-label, dose-escalating trial 40 male AIDS patients with advanced Kaposi sarcoma were enrolled to receive intravenous "stealth" liposomal doxorubicin biweekly at doses of 10 mg/m2 (n = 10), 20 mg/m2 (n = 27), and 40 mg/m2 (n = 3). The median CD4 count at baseline was 25/microL. After six cycles (12 weeks), 39 patients were evaluable. Three patients (7.5%) showed a complete response, which was histologically confirmed. A partial response was documented in 33 patients (85%). Stable disease was observed in three patients (7.5%). During a median treatment duration of 25 weeks, four patients developed stomatitis (10%), and four patients (10%) experienced alopecia. The most frequent hematologic toxicity was neutropenia. Grade 4 neutropenia was seen in 42.5%, and grade 3 toxicity was seen in 30%. Toxicity was dose-dependent and more frequent in the 40 mg/m2 stratum. During a median observation period of 25 weeks, opportunistic infections occurred in 57.5% of the patient population. We conclude that liposomal doxorubicin at dose levels of 10 and 20 mg/m2 is safe and effective for treatment of advanced Kaposi sarcoma in AIDS. A controlled trial comparing liposomal doxorubicin to conventional combination therapy is underway.
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PMID:Liposomal doxorubicin in the treatment of advanced AIDS-related Kaposi sarcoma. 815 40

Pseudomonas aeruginosa infection is unusual in individuals with human immunodeficiency virus infection, and it most often occurs in the setting of other risk factors, such as neutropenia or cytotoxic drug use. We noted an increasing number of pulmonary isolates of this organism in our clinic population and sought to describe the clinical correlates of this finding. Our study consisted of a retrospective review of the microbiology, radiology, and clinical records of 1,852 HIV-seropositive adults seen at a university-based outpatient AIDS clinic. We identified 16 individuals with Pseudomonas bronchopulmonary infection. All subjects had advanced HIV disease with prior AIDS diagnoses, and mean CD4 counts of 25/mm3 (0.025 x 10(9)/L). Pseudomonas was the sole pulmonary pathogen in 14 of 16 patients and was associated with new chest X-ray abnormalities in 14 cases. Four individuals had acute pseudomonal pneumonia with sepsis; this presentation was associated with hospitalization and other known risk factors for Pseudomonas infection. In contrast, 12 patients had more indolent, community-acquired infection, which had a low mortality rate and occurred in the absence of other risk factors. Survivors of the initial bout of Pseudomonas infection had an 86% relapse rate despite a median survival of only 4.5 months. This pattern of pseudomonal disease is reminiscent of cystic fibrosis and suggests a role for maintenance therapy.
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PMID:Pseudomonas aeruginosa bronchopulmonary infection in late human immunodeficiency virus disease. 821 56

Invasive aspergillosis recently has been encountered in adults and children with human immunodeficiency virus (HIV) infection even without known risk factors, such as neutropenia or corticosteroid therapy. Macrophages play a significant role in the host defenses against Aspergillus organisms by ingesting conidia and preventing their germination to hyphae. The antifungal activity of peripheral blood monocyte-derived macrophages (MDM) from 19 HIV-infected children was compared with that of 16 normal controls. The phagocytic activity of patients' MDM, measured as percentage of phagocytosis, was significantly decreased compared with normal donors (P = .014). In addition, the inhibitory activity of MDM on germination of intracellular A. fumigatus conidia was significantly impaired in patients compared with normal controls (P = .016). There was no significant difference in the defects between patients with lower or higher CD4 lymphocyte counts. Impairment of antifungal activity of macrophages may contribute to the susceptibility of HIV-infected patients to aspergillosis.
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PMID:Defective antifungal activity of monocyte-derived macrophages from human immunodeficiency virus-infected children against Aspergillus fumigatus. 824 47

HIV DNA was detected by the polymerase chain reaction technique in polymorphonuclear neutrophils (PMNs) in 11 of 37 (29.7%) HIV-infected patients. A detectable level of HIV DNA in PMNs was more common in symptomatic than asymptomatic HIV infected patients (46.7% and 18.2%, respectively; p < 0.05). HIV DNA in PMNs was detected most frequently in patients with recurrent bacterial pneumonia or Pneumocystis carininii pneumonia. An association between HIV DNA in PMNs and a low CD4/8 ratio as well as high levels of immunoglobulins in the sera was noted. Detectable HIV DNA was found more frequently in patients with neutropenia than in those with a normal level of neutrophils in peripheral blood (44.4% and 28.0%, respectively; p < 0.05). These data suggest that infection of PMNs by HIV may be associated with PMN impairment during HIV infection.
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PMID:Clinical significance of HIV DNA in polymorphonuclear neutrophils from patients with HIV infection. 838 51

Human immunodeficiency virus (HIV)-infected patients may acquire invasive aspergillosis without previously recognized risk factors, such as neutropenia or corticosteroid therapy. Because neutrophils (PMNL) are an important component of host defense in aspergillosis, the antifungal activity of PMNL against hyphae of Aspergillus fumigatus in 31 HIV-infected children was assessed. Hyphal damage was unaffected in 15 HIV-infected children with age-adjusted CD4 cell counts > or = 25% of the normal median value; it was decreased in 16 with CD4 cell counts < 25% (both vs. 20 healthy controls, P = .001. Incubation with sera from 12 of 14 HIV-infected children but not with the recombinant HIV proteins gp120, gp41, and p24 suppressed antifungal activity of normal PMNL compared with normal serum (P = .002). Pretreatment of defective PMNL from 5 patients with granulocyte colony-stimulating factor (G-CSF) partially corrected the defect (P = .002). These findings suggest that impaired serum-mediated antifungal activity against Aspergillus hyphae exists in PMNL of HIV-infected patients with low CD4 cell counts; G-CSF may improve this activity.
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PMID:Impairment of neutrophil antifungal activity against hyphae of Aspergillus fumigatus in children infected with human immunodeficiency virus. 845 Feb 55

Zidovudine is a dideoxynucleoside analogue of thymidine. It acts by interfering with viral reverse transcriptase, thereby inhibiting human immunodeficiency virus (HIV) replication. Zidovudine has been shown in clinical trials to prolong survival of patients with acquired immune deficiency syndrome (AIDS) and advanced AIDS-related complex (ARC), and to delay progression to ARC or AIDS in patients with earlier disease. At the present time it is suggested that zidovudine be initiated when the CD4 lymphocyte count is less than 500 cells/mm3. Recent studies have suggested a delay in the development of AIDS in patients with CD4 counts over 500 cells/mm3, but ongoing studies will require confirmation. The adverse reactions associated with zidovudine have been well described. It appears that haematological toxicity is associated with both the dose and stage of disease. Anaemia may present more often within the first 3 months of therapy, whereas neutropenia can occur early or late. Mild headache and gastrointestinal intolerance may occur early and in some cases limit tolerance to the drug. A number of neurological adverse reactions have been reported rarely including seizures and dose-reduction encephalopathy. The most significant late adverse reaction is that of myopathy, which occurs in patients receiving zidovudine for more than 6 months. With careful monitoring, the adverse reactions of zidovudine are manageable and patient tolerance of the medication is acceptable.
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PMID:Zidovudine toxicity. Clinical features and management. 848 Dec 17

Twenty-nine patients were enrolled in a phase I dose-escalating tolerance trial of N-butyl-deoxynojirimycin, an alpha-glucosidase I inhibitor that inhibits human immunodeficiency virus (HIV)-1 replication by altering glycosylation of gp120. Dosing was begun at 8 mg/kg/day and subsequent doses were 16, 32, 48, and 64 mg/kg/day. The maximum tolerated dose was not achieved because of slow accrual and because the study was stopped after the finding of cataracts in initial long-range rat toxicology studies. These cataracts were later shown to be transient and not found in other animals. The most common side effects were gastrointestinal, with diarrhea and flatulence occurring in most subjects, which seemed to partially improve on a modified diet that excluded complex carbohydrates. Grade III elevations in liver function tests were seen in two patients. Grade III leukopenia and neutropenia were seen in seven patients, but were only severe enough in two to require discontinuation. No significant trends in CD4 cell counts or HIV-1 p24 levels were noted.
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PMID:The tolerability and pharmacokinetics of N-butyl-deoxynojirimycin in patients with advanced HIV disease (ACTG 100). The AIDS Clinical Trials Group (ACTG) of the National Institute of Allergy and Infectious Diseases. 854 34

To assess safety, antitumor response, and immunological and virological activity of interferon-alpha 2a and zidovudine combination therapy in patients with AIDS-related Kaposi's sarcoma, we conducted an open-label, Phase II, multicenter study. Sixty-three patients with biopsy-proven Kaposi's sarcoma and no previous interferon-alpha therapy received zidovudine 600 mg/day and interferon-alpha 2a 18 x 10(6) U/day. The median duration of follow-up was 49 weeks. Of 62 evaluable patients, 25 (40%; 95% confidence interval, 0.28-0.52) showed a complete (26%) or partial (15%) antitumor response. Eight of 30 patients (27%) with < 100 CD4 cells/mm3 and 17 of 32 patients (53%) with > or = 100 CD4 cells/mm3 had a response. The median time to response was 36 weeks. Of the 25 patients with a response, four developed tumor progression. The median duration of response was 22.4 weeks. Eight patients (13%) developed another AIDS-defining event and 13 (21%) died. The major toxicities included anemia (16%), neutropenia (27%), elevated serum transaminases (16%), weight loss (16%), malaise (14%), fatigue (14%), fever (10%), and headache (6%). Therapy with intermediate-dose interferon-alpha 2a and zidovudine resulted in tumor regression in patients with AIDS-related Kaposi's sarcoma who had a wide range of CD4 cell counts; this therapy was relatively well tolerated.
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PMID:A phase II study of recombinant human interferon-alpha 2a and zidovudine in patients with AIDS-related Kaposi's sarcoma. AIDS Clinical Trials Group. 860 Dec 24

Recombinant human granulocyte colony-stimulating factor (G-CSF) has been used to treat neutropenia in patients with cancer and HIV disease. Since lymphocyte counts have been reported to increase with G-CSF therapy, we studied the effect of G-CSF on lymphocyte subsets in HIV-infected patients. Six patients with HIV-associated neutropenia were treated with G-CSF and had significant increases in white blood cell counts. G-CSF induced a significant rise in total lymphocytes, total T-cells, CD8 T-cells, and natural killer cells. A smaller but statistically significant increase in CD4 T-cells and cytotoxic CD8 T-cells was also noted. We conclude that G-CSF has the ability to raise lymphocyte subset levels in patients with HIV disease. The potential immunologic benefit of G-CSF therapy merits further investigation.
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PMID:Increase in lymphocyte subsets following treatment of HIV-associated neutropenia with granulocyte colony-stimulating factor. 862 Jun 26


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