ABSTRACT
The safety profile, tolerability, pharmacodynamics, and pharmacokinetics of four doses of recombinant human granulocyte colony-stimulating factor (filgrastim) were assessed in healthy volunteers in a double-masked, placebo-controlled, parallel-group trial. Healthy subjects received subcutaneous injections of filgrastim 75 microg (n = 8), 150 microg (n = 4), 300 microg (n = 4), 600 microg (n = 8), or placebo (n = 6) daily for 10 consecutive days. Blood samples were drawn daily immediately before the injection and on days 1 and 10 serially throughout the day. Increased absolute neutrophil counts (ANCs) were seen within 90 minutes of drug administration in subjects in all dose groups, peaking approximately 12 hours after administration. This increase was dose related in subjects in the three lower dose groups. The time to peak ANC on day 10 was approximately 9 hours, with a daily ANC profile in all four dose groups that was similar to the profile on day 1. In all dose groups, ANCs were near baseline within 48 hours of discontinuation of filgrastim. Mild, reversible thrombocytopenia was reported in 4 of 10 subjects in the highest dose group. Two subjects in the filgrastim 600-microg group were withdrawn for adverse events. Filgrastim had a good safety profile and caused dose-related increases in ANC when administered to healthy volunteers for up to 10 days.
Subject(s)
Granulocyte Colony-Stimulating Factor/administration & dosage , Neutrophils/drug effects , Adult , Dose-Response Relationship, Drug , Double-Blind Method , Filgrastim , Granulocyte Colony-Stimulating Factor/blood , Granulocyte Colony-Stimulating Factor/pharmacokinetics , Humans , Leukocyte Count/drug effects , Male , Neutrophils/cytology , Placebos , Recombinant ProteinsABSTRACT
This paper reports on the results of a study conducted in 1994. The aim of the study was to gain insight into nurses' perceptions of ethical dilemmas concerning informational privacy of patients with hiv/aids. The chosen research method was descriptive, from a qualitative research perspective (Grounded Theory). The purposive sample consisted of seven nurses working in a university hospital. Data were collected by means of in-depth interviews and the critical incidents method. The description of the dilemmas led to a central theme: the nurses' choice whether or not to give information revealing the diagnosis seropositivity or aids to patient's relatives or partner. The core categories were derived from analysis of the descriptions given by the nurses. They are split up into experiences of the nurses and the way nurses cope with these dilemmas. Recommendations are given for promotion of expertise and education.
Subject(s)
Acquired Immunodeficiency Syndrome/nursing , Confidentiality , Ethics, Nursing , HIV Infections/nursing , Adaptation, Psychological , Adult , Emotions , Female , Humans , Male , Nursing Evaluation Research/methods , Nursing Staff, Hospital/psychology , PerceptionABSTRACT
Atevirdine is a nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1). In this study we investigated the effect of atevirdine in asymptomatic antiretroviral naive HIV-infected patients with CD4+ cell counts of between 200 and 750 cells per mm3. Patients were randomized to receive 600 mg of atevirdine (n = 15) or a placebo (n = 15) three times a day for 12 weeks. There was no statistically significant effect of atevirdine on viral loads (HIV p24 antigen and HIV-1 RNA levels by PCR) or CD4+ cell counts. The data do not support the use of atevirdine as a monotherapy in the treatment of HIV-infected patients.
Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , Piperazines/therapeutic use , Adult , Anti-HIV Agents/adverse effects , CD4 Lymphocyte Count , Double-Blind Method , HIV Infections/immunology , HIV Infections/virology , Humans , Male , Piperazines/adverse effectsABSTRACT
Atevirdine mesylate (U-87201E) is a new nonnucleoside (bisheteroarylpiperazine) inhibitor of human immunodeficiency virus type 1 reverse transcriptase. In a double-blind, escalating single-dose study the safety, tolerance, and pharmacokinetics of atevirdine mesylate were investigated in 24 asymptomatic human immunodeficiency virus-seropositive male patients. Each patient received one single oral dose of atevirdine mesylate and placebo separated by an interval of 1 to 3 weeks. For each dose level (400, 800, 1,200, and 1,600 mg) six patients received drug and placebo on separate occasions. Blood samples were collected before dosing and at intervals afterward for safety evaluation and estimation of atevirdine and metabolite levels. The concentrations of atevirdine and its principal metabolite (U-89255) in serum were determined by high-performance liquid chromatography. The results of the study showed that atevirdine mesylate is well tolerated at all dose levels. No clinically significant effects on vital signs, electrocardiograms, or laboratory tests were observed. Occasional headache and nausea were reported both in the drug group and in the placebo group. The times to peak values were relatively short (0.5 to 1.0 h), suggesting a rapid absorption. The maximum concentrations of drug in serum were 1.4 microM (400 mg), 4.2 microM (800 mg), 7.3 microM (1,200 mg), and 5.8 microM (1,600 mg). The values of the pharmacokinetic parameters for atevirdine were found to have relatively large intersubject variabilities, and consequently, the study had little power to detect dose-dependent changes in the values of the pharmacokinetic parameters. The oral clearance of atevirdine tended to increase by 90% as the atevirdine mesylate doses increased from 400 to 1,600 mg, but this change in oral clearance was not statistically significant. The values of the pharmacokinetic parameters determined in the study were similar to those found in a previous single-dose study in healthy volunteers.
Subject(s)
Antiviral Agents/adverse effects , Antiviral Agents/pharmacokinetics , HIV Seropositivity/metabolism , HIV-1 , Piperazines/adverse effects , Piperazines/pharmacokinetics , Adult , Double-Blind Method , Humans , Male , Middle AgedABSTRACT
We studied the usefulness of the in vitro lymphoproliferation assay and the in vivo skin test in HIV-1-infected patients by using Clostridium tetani and tuberculin as testing antigens. Moreover, the relationship between data obtained from both assays was studied. In 56 HIV-infected patients not receiving antiretroviral therapy CD4+ cell counting was performed. In addition, in vitro (lymphocyte proliferation assay) and in vivo (delayed type hypersensitivity skin test) measuring of the immune status was done using C. tetani and tuberculin as testing antigens. When using C. tetani a significant correlation between the results of both tests and the CD4+ cell count was found. In contrast to earlier reports from African countries, in vivo skin testing using tuberculin did not yield clinically significant information on the degree of immunodeficiency. We explain our findings by the fact that health care policy in The Netherlands encompasses vaccination with C. tetani, which enables the application of C. tetani as testing antigen for measuring immune function both in vitro and in vivo.
Subject(s)
Acquired Immunodeficiency Syndrome/immunology , HIV-1 , Antigens, Bacterial/administration & dosage , CD4-Positive T-Lymphocytes/cytology , Cell Count , Clostridium tetani/immunology , Humans , Hypersensitivity, Delayed/immunology , Immunity, Cellular , Lymphocyte Activation , Lymphocytes/physiology , Skin Tests/methods , Tetanus Toxoid/pharmacology , Tuberculin/pharmacologyABSTRACT
OBJECTIVE: Comparison of the quality of life of asymptomatic (n = 24) and symptomatic (n = 20) HIV-infected patients and description of the changes in quality of life during the symptomatic stage. DESIGN: Prospective study. SETTING: University Hospital Utrecht. METHOD: Every four months questionnaires on quality of life were completed by 44 of 55 consecutive HIV-infected patients. RESULTS: Physically, asymptomatic HIV-infected patients were better off than symptomatic HIV-infected patients; psychologically, however, both groups of patients showed similar responses. During the symptomatic stage the patients' physical functioning diminished further, but feelings of anxiety or depression showed no marked change; self-evaluations of health conditions became slightly more negative with time.
Subject(s)
HIV Infections/psychology , Quality of Life , Academic Medical Centers , Activities of Daily Living , Adult , Depression , Fear , Female , HIV Infections/complications , Humans , Inpatients/psychology , Male , Middle Aged , Prospective Studies , Surveys and QuestionnairesABSTRACT
The treatment of AIDS patients with zidovudine extends their survival time. However, hematological side effects frequently require a reduction of the dosage and the administration of blood transfusions. We reviewed the history of zidovudine treatment and blood transfusions for 27 patients with AIDS treated in the University Hospital Utrecht between July 1st, 1987 and July 1st, 1990. The initial dosage of zidovudine was 1000-1200 mg daily orally. Two months after the initiation of the therapy, 48% of the patients required a reduction of the zidovudine dosage. This percentage had increased to 85% after 12 months since the start of the therapy. During this period, 26% of the patients received blood transfusions. The zidovudine dosage was on the average of 480 mg per day after reduction. One year after the start of the therapy, 81% of the patients were still alive, and after 1 1/2 years this percentage was 68. In our study the proportion of patients undergoing a reduction of the zidovudine dosage was high in comparison with data reported in the literature. However, the need for blood transfusions was clearly lower. The survival percentages after 1 and 1 1/2 years were about the same as reported in other studies. Therefore, we conclude that an early reduction of the zidovudine dosage and resulting low total dosage were effective and resulted in a decreased need for blood transfusions.
