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Biomedical subjects

F Valentine

Publications and source records attributed to F Valentine.

At least 19 recordsLinked to original sources
PubMed2001

Residual human immunodeficiency virus (HIV) Type 1 RNA and DNA in lymph nodes and HIV RNA in genital secretions and in cerebrospinal fluid after suppression of viremia for 2 years.

Residual viral replication persists in a significant proportion of human immunodeficiency virus (HIV)-infected patients receiving potent antiretroviral therapy. To determine the source of this virus, levels of HIV RNA and DNA from lymphoid tissues and levels of viral RNA in serum, cerebrospinal fluid (CSF), and genital secretions in 28 patients treated for < or =2.5 years with indinavir, zidovudine, and lamivudine were examined. Both HIV RNA and DNA remained detectable in all lymph nodes. In contrast, HIV RNA was not detected in 20 of 23 genital secretions or in any of 13 CSF samples after 2 years of treatment. HIV envelope sequence data from plasma and lymph nodes from 4 patients demonstrated sequence divergence, which suggests varying degrees of residual viral replication in 3 and absence in 1 patient. In patients receiving potent antiretroviral therapy, the greatest virus burden may continue to be in lymphoid tissues rather than in central nervous system or genitourinary compartments.

Cohort Studies↗
PubMed2000

Shipment impairs lymphocyte proliferative responses to microbial antigens.

Lymphocyte proliferation assays (LPAs) are widely used to assess T-lymphocyte function of patients with human immunodeficiency virus infection and other primary and secondary immunodeficiency disorders. Since these assays require expertise not readily available at all clinical sites, specimens may be shipped to central labs for testing. We conducted a large multicenter study to evaluate the effects of shipping on assay performance and found significant loss of LPA activity. This may lead to erroneous results for individual subjects and introduce bias into multicenter trials.

Candida↗
PubMed1999

Delayed-type hypersensitivity to recombinant HIV envelope glycoprotein (rgp160) after immunization with homologous antigen.

Delayed-type hypersensitivity (DTH) responses to intradermal recombinant HIV envelope glycoprotein (rgp160) may assess cell-mediated immune responses to HIV envelope. In three studies, DTH and lymphocyte proliferation responses to rgp160 were obtained in a total of 106 HIV-seropositive subjects with CD4+ counts >400 cells/mm3. Several subjects participated in more than one study. Before immunization, DTH responses were seen in 5 of 56 (9%) of HIV-infected study subjects. After immunization with an alum-adjuvanted experimental rgp160 vaccine, DTH responses were seen in 46 of 52 (89%). Using in vitro lymphocyte proliferation activity (LPA) to rgp160 as an indication of cellular immune response, skin testing has a sensitivity of 0.75 (95% confidence Interval [CI], 0.59-0.88) and a specificity of 0.84 (95% CI, 0.72-0.92). Biopsy samples of skin that had tested positive confirmed the presence of a DTH reaction with a predominance of CD4+ T cells in the perivascular, inflammatory infiltrate. Skin testing before and after immunization with candidate AIDS vaccines could provide a simple method in the field to assess new cell mediated immune responses.

AIDS Vaccines↗
PubMed1998

The clinical educator role.

Role of the clinical educator is presented. Questionnaire survey of 60 staff was undertaken. Meeting staff's continuing education needs is important. Ensuring roles are responsive to needs of practitioners, children and families is vital. Quality education equals quality services.

Attitude of Health Personnel↗
PubMed1998

Empowerment: family-centred care.

The major findings from interviews with qualified children's nurses, analysed using a grounded theory approach, were that children's nurses have the necessary theoretical knowledge to empower families, but they require educational and training opportunities in family empowerment. It was also established that a working environment that promotes its translation into everyday practice and supports them in an empowering model of care for children and families is necessary.

Adult↗
PubMed1993

On the mechanism of a 60-Hz electric field induced growth reduction of mammalian cells in vitro.

Data on 60-Hz electric field (EF) induced reduction in growth rate of plant roots have strongly supported the hypothesis that the effect is related to an EF-induced transmembrane potential (Vim). An investigation was undertaken to determine if this hypothesis is also applicable to 60-Hz EF-induced reductions in growth rate of mammalian cells in vitro. Human lymphoblastic (RPMI 1788) and human carcinoma (HeLa) cells were selected for study, the former having a relatively small diameter (11.2 microns), and the latter having a relatively large diameter (15.4 microns). The 60-Hz EFs ranged from 430-1200 V/m in the culture medium. The growth rate of RPMI 1788 cells after 4-days was depressed by about 42% at a 60-Hz EF of 1000-1200 V/m with a response threshold occurring at 950 V/m; the Vim at the response threshold was 8 mV. There was no 60-Hz EF-induced effect on HeLa cell growth rate of a Vim of 8 mV (60-Hz EF = 700 V/m); a statistically significant effect was achieved at Vim of 11 mV (950 V/m). The data support the hypothesis that above a threshold 60-Hz EF, Vim acts as the initial signal leading to growth rate reductions.

Cell Division↗
PubMed1992

Extended follow-up of peripheral neuropathy in patients with AIDS and AIDS-related complex treated with dideoxyinosine.

Neuropathic complaints were frequently observed in a Phase I study of dideoxyinosine (ddI) in 44 patients with AIDS and AIDS-related complex. Ten patients (23%) were thought to have a ddI-related peripheral neuropathy. The symptoms were primarily sensory, and there was limited motor involvement. The sensory symptoms improved in all patients with discontinuation of ddI. Some patients tolerated reintroduction of ddI at lower doses without significant recurrence of the neuropathic symptoms. Although the neuropathy was usually seen in patients taking higher doses of ddI than used in current treatment protocols, clinicians must be aware of this potential toxicity as more human immunodeficiency virus-infected patients are being treated with ddI.

AIDS-Related Complex↗
PubMed1990

Toxicity of combined ganciclovir and zidovudine for cytomegalovirus disease associated with AIDS. An AIDS Clinical Trials Group Study.

OBJECTIVE: To assess the toxicity, efficacy, and pharmacology of combined zidovudine and ganciclovir therapy in patients with the acquired immunodeficiency syndrome (AIDS) and serious cytomegalovirus (CMV) disease. DESIGN: Prospective, phase I multicenter trial (ACTG 004) with patients grouped by previous study drug history. SETTING: Three university-based AIDS Clinical Trials Units sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). PATIENTS: Forty-one patients with AIDS-related CMV disease. Previous therapy with either zidovudine or ganciclovir was allowed. INTERVENTIONS: Patients were treated with zidovudine, 600 to 1200 mg/d; or, if on ganciclovir maintenance, ganciclovir, 5 mg/kg body weight; blood was sampled for pharmacokinetic studies. The other drug was then administered to the patient with blood sampling and, finally, the two drugs in combination were given. Patients were continued on both drug therapies with dose reduction of zidovudine only for grade 3 or 4 toxicity. MEASUREMENTS AND MAIN RESULTS: Forty patients were eligible. Hematologic toxicity was frequent, with 9 of the 10 patients requiring dose reductions for grade 3 or 4 toxicity at zidovudine doses of 1200 mg/d. With zidovudine doses of 600 mg/d, 82% experienced such hematologic toxicity. Median survival was 6 months; 10 patients developed intercurrent infection and 19, progressive CMV disease. Pharmacokinetic variables (alpha and beta half-lives, volume of distribution, clearance) were not affected in combination therapy. CONCLUSION: The combination of zidovudine and ganciclovir is poorly tolerated in patients with AIDS and serious-CMV disease, with 82% developing severe to life-threatening hematologic toxicity. Such toxicity is not a result of pharmacologic interactions, drug metabolism, or excretion.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Results of the flow cytometry ACTG quality control program: analysis and findings.

The AIDS Clinical Trial Group's (ACTG) Immunology Committee was charged with initiating a quality control program for all laboratories participating in the ACTG program reporting flow cytometry data. Forty-one laboratories were evaluated. This report defines the goals of this program and the subsequent findings after 19 send-outs were made. Both HIV positive volunteer donors and normal age-matched donors were used. Sample sets included both heparin and EDTA anticoagulated bloods. Laboratories were asked to report hematologic parameters as well as flow cytometry data both in percentages and absolute numbers. Results were evaluated using nonparametric statistical analysis. Robust CVs and interquartile ranges were used to define the performance of individual laboratories for each CD subset analyzed. Intralaboratory reproducibility was analyzed by paired sample sets. All laboratories were found to be able to define normal samples as normal. Seventy-five percent of the laboratories were able to define abnormal samples as abnormal. Twenty-five percent could not identify two abnormal samples as abnormal. Forty percent of the labs were found unable to reproduce paired samples within an absolute of +/- 5%. EDTA was found slightly superior to heparin in bloods evaluated by flow cytometry within 30 hr of collection. The analysis of specific histograms, questionnaires, and data analysis led to a specific set of recommendations for performance of flow cytometry studies.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Studies of the mechanisms of action of the antiretroviral agents hypericin and pseudohypericin.

Administration of the aromatic polycyclic dione compounds hypericin or pseudohypericin to experimental animals provides protection from disease induced by retroviruses that give rise to acute, as well as slowly progressive, diseases. For example, survival from Friend virus-induced leukemia is significantly prolonged by both compounds, with hypericin showing the greater potency. Viremia induced by LP-BM5 murine immunodeficiency virus is markedly suppressed after infrequent dosage of either substance. These compounds affect the retroviral infection and replication cycle at least at two different points: (i) Assembly or processing of intact virions from infected cells was shown to be affected by hypericin. Electron microscopy of hypericin-treated, virus-producing cells revealed the production of particles containing immature or abnormally assembled cores, suggesting the compounds may interfere with processing of gag-encoded precursor polyproteins. The released virions contain no detectable activity of reverse transcriptase. (ii) Hypericin and pseudohypericin also directly inactivate mature and properly assembled retroviruses as determined by assays for reverse transcriptase and infectivity. Accumulating data from our laboratories suggest that these compounds inhibit retroviruses by unconventional mechanisms and that the potential therapeutic value of hypericin and pseudohypericin should be explored in diseases such as AIDS.

Animals↗
PubMed1989

Phase I/II trial of thymostimulin in opportunistic infections of the acquired immune deficiency syndrome.

Fifteen patients with acquired immune deficiency syndrome (AIDS) and opportunistic infection, were randomized to receive treatment with either thymostimulin (TP-1) at 1 mg/kg for 14 days then weekly for 12 weeks or placebo. The objectives of this study were to evaluate the toxicity of TP-1 in this patient population and to make observations on clinical response as measured by time to second opportunistic infection (OI) and changes in laboratory parameters of immune function. The study demonstrates that TP-1 can be administered safely. There were no differences, however, in time to second OI or overall survival between patient groups. In addition, no change in the immune function could be detected in patients receiving thymostimulin.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Prevalence of HIV infection in New York call girls.

In order to evaluate the frequency of sexual transmission of human immunodeficiency virus (HIV) among promiscuous heterosexuals, we studied the prevalence of HIV infection among a group of predominantly Caucasian call girls and women working for escort services and massage parlors in New York City. In the 78 subjects studied, the mean age was 31.6 years and the mean duration of prostitution was 5.1 years. Study participants each had a median of 200 different sexual partners in the preceding year. Six women had a history of intravenous drug abuse and none had a history of any other recognized risk factor for HIV infection. Ninety percent of the women studied used condoms during intercourse with at least some of their partners. One of the six women with a history of drug abuse and none of the 72 non-drug-abusers were seropositive for HIV. This study indicates that despite their promiscuity, HIV infection is still uncommon in call girls in New York City.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Detection of HIV antigen and specific antibodies to HIV core and envelope proteins in sera of patients with HIV infection.

The sera of well-characterized populations were examined for three markers of human immunodeficiency virus (HIV) infection; HIV antigen (HIV Ag), and antibodies to HIV envelope (gp41) and core (p24) proteins. Of 563 serum samples tested, 251 were from HIV-infected patients diagnosed as having AIDS manifested by opportunistic infections (AIDS-OI), AIDS-associated Kaposi's sarcoma (AIDS-KS), or AIDS-related complex (ARC). One hundred seventy-six specimens tested were from asymptomatic high-risk individuals, and 136 were from heterosexual control subjects or patients with non-AIDS-related disease. None of the 136 control individuals tested had HIV Ag or HIV antibodies to either p24 or gp41. Of the 427 HIV-seropositive individuals, 99% to 100% were positive for gp41 antibodies to HIV. In contrast, the seroprevalence of p24 antibodies to HIV varied from 23% to 83% and appeared to be inversely associated with the severity of the patients' clinical symptoms. When specimens were analyzed for the presence of HIV Ag, in seropositive individuals the prevalence rate for this marker was lowest (1.4%) in asymptomatic individuals and highest (50%) in the AIDS-OI diagnosed group. Also, 240 cases with AIDS-KS, AIDS-OI, and ARC and the group of asymptomatic high-risk individuals were analyzed for T helper/T lymphocytes (T4) cell number and T4/T8 ratio; only one (2.0%) HIV Ag-positive case showed a T4 cell number greater than 400 and a normal T4/T8 ratio. These studies appear to demonstrate a direct correlation between the presence of HIV Ag and the severity of clinical complications of HIV infection.

Antibodies, Viral↗
PubMed1985

Immunophenotype of human melanoma cells in different metastases.

The pattern of melanoma-associated antigens (MAAs) expressed on the surface of melanoma cells in 23 metastases, 15 obtained from different patients and 8 from different metastases in two patients, was studied by immunoprecipitation and sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis using monoclonal and polyclonal melanoma antisera. Though there were differences in the MAAs expressed by each melanoma, there were marked similarities as well. No more than two melanomas had a similar pattern of MAAs. However, all melanomas expressed some MAAs, and most MAAs were commonly expressed by several melanomas. Two of the MAAs studied, with molecular weights of approximately 75,000 and 95,000 to 97,000, were particularly well represented, and at least one of these two antigens was expressed by all melanoma cells. These results suggest that complete absence of tumor-associated antigens on metastatic melanoma cells is a rare phenomenon. All melanoma lines we studied expressed at least one of a restricted number of antigens. Thus despite antigenic heterogeneity, sufficient similarity remains between different melanomas to permit specific immunotherapy to be targeted to a limited number of tumor antigens.

Animals↗
PubMed1984

Reduced Langerhans' cell Ia antigen and ATPase activity in patients with the acquired immunodeficiency syndrome.

We investigated the possible role of a defect in antigen-presenting cells in the acquired immunodeficiency syndrome (AIDS), by enumeration of Langerhans' cells, the epidermal antigen-presenting cells. These cells were stained for the characteristic markers, surface Ia antigen and surface ATPase activity. A significant reduction was observed in the number of stained cells per square millimeter of body-surface area in 24 patients with AIDS and either opportunistic infections (Ia, 258 +/- 34, and ATPase, 274 +/- 46) or Kaposi's sarcoma (Ia, 378 +/- 100, and ATPase, 530 +/- 26), as compared with 38 appropriate controls (Ia, 721 +/- 13, and ATPase, 693 +/- 12). Examination of six patients with an "AIDS-related complex" revealed significantly reduced numbers of Langerhans' cells per square millimeter; this reduction was more pronounced in staining for Ia antigen (306 +/- 69) than in staining for ATPase activity (517 +/- 101). Given the known role of Ia expression in antigen presentation, we suggest that functional alterations in Langerhans' cells, and perhaps also in antigen-presenting cells in tissues other than skin, may be involved in the pathogenesis of AIDS.

Acquired Immunodeficiency Syndrome↗