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Biomedical subjects

A Cargnel

Publications and source records attributed to A Cargnel.

At least 37 records · Page 2Linked to original sources
PubMed1999

A randomized, double-blind trial on the use of a triple combination including nevirapine, a nonnucleoside reverse transcriptase HIV inhibitor, in antiretroviral-naive patients with advanced disease.

The immunologic and virologic activity of nevirapine in combination with two nucleosides (zidovudine [ZDV] and didanosine [ddI]) was evaluated in antiretroviral-naive patients with a CD4 count <200/mm3 or clinical AIDS. In all, 68 patients were enrolled in a 48-week double-blind, placebo-controlled trial. A group of 32 patients received ZDV + ddI + nevirapine, and 36 patients received ZDV + ddI. Primary efficacy parameters were the activity on HIV-1 RNA and on peripheral blood CD4+ cells, with differences between groups analyzed by the Wilcoxon's nonparametric two-sample test. Baseline RNA was high in both treatment groups (median values, 5.8 and 5.7 log10). RNA and CD4 responses were significantly higher with the triple combination (median RNA reductions, 2.69 versus 1.05 log10 at 24 weeks and 1.97 versus 1.20 log10 at 48 weeks; median CD4 increases, 81 versus 64 cells/mm3 at 24 weeks and 101 versus 27 cells/mm3 at 48 weeks). This study demonstrates that a triple combination of ZDV + ddI + nevirapine used as first-line regimen in antiretroviral-naive patients can induce sustained virologic and immunologic response in patients with low CD4 count or a previous diagnosis of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Detection of rat Pneumocystis carinii proteinases and elastase and antipneumocystis activity of proteinase inhibitors in vitro.

Proteinases play an important role in survival of microorganisms and in pathogenicity of diseases. By using a modified SDS-gelatin-polyacrylamide gel system, proteinases of rat-P.carinii were detected as bands of proteolytic digestion after electrophoresis. P.carinii organisms obtained from dexamethasone immunosuppressed transtracheally infected rats were cultured in spinner flask suspension cultures to minimize host cell contamination. At pH 8.3, seven Pc-specific proteolytic bands were detected in three clusters of different molecular weights clearly different from host cell patterns. By using a range of pH, various preparations of organisms and both infected and uninfected culture media, proteolytic activities have been partially characterized. Elastase secretion has been assessed based on elastin digestion model. Proteinase inhibitors have been tested for their ability to inhibit P.carinii growth in HEL299 short-term monolayer cultures. Results indicate that proteolytic activities are involved in the proliferation of microorganisms since leupeptin exerted in vitro antipneumocystis activity while aprotinin enhanced P.carinii growth.

Animals↗
PubMed1999

Outcome of multidrug-resistant tuberculosis in human immunodeficiency virus-infected patients.

Among 324 cases of culture-proven tuberculosis from 1988 to 1996 in a hospital in Milan, Italy, 90 (27.8%) were due to Mycobacterium tuberculosis strains resistant to isoniazid and rifampin. Sixty-one of 69 isolates tested had identical restriction fragment length polymorphism patterns. The prevalent strain tested susceptible only to ethionamide and was also resistant to ethambutol, streptomycin, cycloserine, amikacin, kanamycin, terizodone, ofloxacin, rifabutin, rifapentin, and KRM 1648. The median survival time was 94 days. Multivariate analysis showed a trend toward better outcome in the period 1994-1996 (hazard ratio, 4.16; P<.001), and extrapulmonary localization of tuberculosis was the only other independent predictor of a negative outcome (hazard ratio, 2.1; P = .019). The delay from symptoms to beginning of therapy did not seem to be a determining factor in survival time. Standard antituberculosis therapy with four drugs (isoniazid, rifampin, ethambutol, and pyrazinamide) had a higher efficacy than did other regimens with fewer drugs but without a statistically significant difference.

AIDS-Related Opportunistic Infections↗
PubMed1999

Comparison of once and twice daily dosing of didanosine in combination with stavudine for the treatment of HIV-1 infection. AI 454-146 Team.

OBJECTIVE: To compare the antiviral activity, safety and tolerability of didanosine dosed once and twice daily when administered in combination with stavudine dosed twice daily in human immunodeficiency virus type 1 (HIV-1)-infected individuals with little or no previous exposure to antiretroviral drugs. DESIGN: Comparative, multicentre, randomized, open-label, short-term study. PATIENTS AND METHODS: Eighty-four HIV-1-infected adults with qualifying baseline CD4 cell counts of 200 to 500 cells/mm3 were included in the study. Of these, 43 patients received once daily didanosine plus twice daily stavudine (group A) and 41 subjects received twice daily didanosine plus twice daily stavudine (group B). The primary efficacy analysis used was the time-averaged difference (TAD) between treatment regimens of variations in plasma HIV-1 RNA levels from baseline over the first 12 weeks of therapy. Plasma HIV-1 RNA levels, CD4 cell counts and adverse events were monitored. RESULTS: At week 12, median HIV-1 RNA variations were -1.18 log10 copies/ml in group A and -0.88 log10 copies/ml in group B. For patients who were followed up to week 24, median variations of HIV-1 RNA levels from baseline were -1.21 log10 copies/ml in group A and -0.78 log10 copies/ml in group B. The TAD between the two treatment groups for variations from baseline plasma HIV-1 RNA levels over the first 12 weeks was 0.10 log10 copies/ml (95% confidence interval, -0.19 to 0.40), indicating equivalence. CONCLUSION: Once daily didanosine plus twice daily stavudine and twice daily didanosine plus twice daily stavudine are equally effective in reducing plasma HIV-1 RNA levels and increasing CD4 cell counts. Both regimens are safe and well tolerated.

Adult↗
PubMed1998

Combined use of blood and oropharyngeal samples for noninvasive diagnosis of Pneumocystis carinii pneumonia using the polymerase chain reaction.

To evaluate the clinical use of a polymerase chain reaction (PCR) assay for diagnosis of Pneumocystis carinii pneumonia (PCP) using samples collected noninvasively, the Internal Transcribed Spacers (ITSs) nested PCR was performed on 148 samples from 40 subjects. Bronchoalveolar lavage (BAL) fluid sera, gargled oropharyngeal washes, and peripheral blood mononuclear cells (PBMC) from 14 AIDS patients (mean age, 35.6 years; mean CD4+ cell count, 49.2 cells/mm3) with proven PCP and from 13 HIV-seropositive controls (mean age, 34.6 years; mean CD4+ cell count, 107.3 cells/mm3) with other AIDS-related opportunistic infections were evaluated. Sera and oropharyngeal samples were also collected from 13 HIV-seronegative health care personnel working in an infectious disease ward for use as negative controls. The ITSs nested PCR confirmed the morphological diagnosis of PCP in all patients when BAL fluid was tested (100% sensitivity). This technique also detected Pneumocystis carinii DNA in oropharyngeal samples from 78.6% of patients, in sera from 71.4% of patients, in PBMC from 35.7% of patients. When all results obtained after ITSs nested PCR were considered together for the same patient, the sensitivity for PCP diagnosis was 100% for blood and oropharyngeal samples (gargled saline), as confirmed by subsequent BAL. All samples collected noninvasively from 26 of 26 controls were negative using ITSs nested PCR (100% specificity).

AIDS-Related Opportunistic Infections↗
PubMed1998

Current in vitro culture systems for Pneumocystis.

Although Pneumocystis continuous culture systems have not yet been developed, efficient short-term in vitro methods allowing the production of infectious forms of Pneumocystis can now be employed. The quality of the inoculum will influence the in vitro development of P. carinii. For this reason, efficient extraction and cryopreservation techniques are considered in this section. In vitro growth and limited passage were obtained by inoculating freshly extracted parasites onto fibroblast- or epithelial-like cell monolayers cultivated in ordinary tissue culture flasks, culture plates, microcarrier beads or other culture devices. Cultures were usually maintained in an atmosphere of 5% CO2 at 35-37 degrees C. The results obtained in these different systems were surprisingly similar: the number of parasites increased about 6-10 times within the first 3-4 days post-inoculation, then remained stationary until day 7-14 and decreased rapidly. If passages were attempted, the growth decreased gradually and no growth was recorded after 2-3 passages. Proof of the in vitro Pneumocystis attachment to feeder cells has been furnished by electron microscopy. Two currently used feeder cell culture systems were selected in this subchapter. The first system is a co-culture of monolayer lung epithelial-like cells with Pneumocystis. After trypsin treatment and passage of cells with attached parasites to culture bottles containing fresh medium, 3 or more new culture bottles can be plated. A 2-4-fold increase in parasite number can be obtained but, interestingly, cultured parasites were more infectious to the nude rat than freshly extracted lung parasites. In the second system, the spinner flask culture method, Pneumocystis is cultivated on cell coated microbeads in slow stirring vessels, in order to exploit the beads' huge surface where microorganisms can transiently adhere and grow and from where they can be easily detached by simply leaving the beads to settle down. This culture system has ensured 10(8)-10(9) viable trophozoites in each harvest after 7-10 days of slow stirring incubation.

Animals↗
PubMed1998

In vitro drug assays and statistical analysis.

The development of in vitro drug tests to assess the efficacy of drugs against Pneumocystis carinii has been hindered by the lack of efficient methods for continuous cultivation of the microorganism. However, different short-term culture systems have been proposed by many teams. In the present contribution an in vitro microplate drug assay and two statistical programs allowing the analysis of results are presented.

Algorithms↗
PubMed1998

Update on Pneumocystis carinii f. sp. hominis typing based on nucleotide sequence variations in internal transcribed spacer regions of rRNA genes.

Pneumocystis carinii f. sp. hominis isolates from 207 clinical specimens from nine countries were typed based on nucleotide sequence variations in the internal transcribed spacer regions I and II (ITS1 and ITS2, respectively) of rRNA genes. The number of ITS1 nucleotides has been revised from the previously reported 157 bp to 161 bp. Likewise, the number of ITS2 nucleotides has been changed from 177 to 192 bp. The number of ITS1 sequence types has increased from 2 to 15, and that of ITS2 has increased from 3 to 14. The 15 ITS1 sequence types are designated types A through O, and the 14 ITS2 types are named types a through n. A total of 59 types of P. carinii f. sp. hominis were found in this study.

Base Sequence↗
PubMed1997

Does immunoglobulin interfere with the immunogenicity to Pasteur Mérieux inactivated hepatitis A vaccine?

BACKGROUND/AIMS: The aim of this study was to compare the immunogenicity of Pasteur Mérieux (P.M. s.v.) inactivated hepatitis A vaccine when given alone with its immunogenicity when given in combination with immunoglobulin. METHODS: We enrolled 80 healthy volunteers who were seronegative for anti-HAV. Forty subjects (group A) were given two doses of vaccine at 0 and 6 months plus 4 ml of immunoglobulin given simultaneously with the first vaccine injection; and 40 subjects (group B) were given vaccine alone. The population characteristics (age, sex, height and weight) of the two groups were comparable. RESULTS: Anti-HAV antibody was detectable at week 1 in 100% of group A and in 5.7% of group B, and in 100% of both groups at 4 and 8 weeks. Seroconversion rates (> or = 20 mIU/ml) were 97.4% in group A and 100% in group B at week 24 and were 100% in both groups 4 weeks after a booster injection at 6 months. The antibody response level was lower after concomitant administration of vaccine with immunoglobulin. The antibody geometric mean titer was higher at week 1 in subjects who had been given vaccine and immunoglobulin, but nearly 50% lower at week 4 and thereafter, indicating inhibition of the vaccine-induced immune response by immunoglobulin. At week 28, i.e. 4 weeks after the booster injection, geometric mean titers had increased about 13-15 times in both groups, reaching highly protective antibody levels (3351 mIU/ml in group A and 5843 mIU/ml in group B). No serious adverse effects were observed during the follow-up. CONCLUSIONS: These data indicate that P.M. s.v. hepatitis A vaccine is highly immunogenic and safe, even when given simultaneously with immunoglobulin. Despite the interference of the immunoglobulin with the active immune response, individuals who were immunized passively plus actively also developed high titers of anti-HAV antibody. It is therefore reasonable to expect that this inhibition will not affect the overall protection conferred by the vaccine.

Adult↗
PubMed1997

A randomized trial (ISS 902) of didanosine versus zidovudine in previously untreated patients with mildly symptomatic human immunodeficiency virus infection.

In this multicenter study (ISS 902), 554 previously untreated patients with <500 CD4 cells/mm3 and mildly symptomatic human immunodeficiency virus disease were randomized to receive zidovudine or didanosine (ddI). After a mean follow-up of 20 months, 80 patients (40 zidovudine, 40 ddI) had died and 146 had at least one AIDS-defining event (73 zidovudine, 73 ddI). Overall, no difference was found between treatments with respect to progression to AIDS or death. The analysis of relative risk (RR) of progression over time, however, showed an initially minor risk for zidovudine patients and an inversion in the zidovudine-ddI RR in the second and third years of follow-up. Didanosine showed a greater effect on CD4 cell count response. The two drugs confirmed the toxicity patterns already reported in other trials, with a low occurrence of pancreatitis (ddI 1.3%, zidovudine 0.4%). The overall results suggest that, in this population, zidovudine and ddI monotherapies have comparable long-term clinical efficacy and that more powerful regimens should be preferred.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Hepatic histology of patients with HIV infection and chronic hepatitis C treated with interferon.

AIMS: To evaluate the histological changes seen in liver biopsies after interferon (IFN) treatment in patients with chronic hepatitis C and human immunodeficiency virus (HIV) infection. METHODS: Twenty four intravenous drug users with chronic hepatitis C were investigated histologically before beginning a 12 month course of IFN treatment and 18 months later. Twelve were HIV positive, without opportunistic or other viral infections (group A), and 12 were HIV negative (group B). RESULTS: According to alanine amino-transferase concentrations, four sustained responders and eight non-responders were found in group A; six sustained responders, five relapsers, and one non-responder were found in group B. HCV RNA became negative in one sustained responder of group A and in the six sustained responders of group B. When histological findings of biopsies performed before therapy and 18 months later were compared, no significant changes in the mean value of Knodell's index and subindices were found in group A, whereas in group B Knodell's index, piecemeal necrosis, and focal hepatocellular necrosis decreased significantly. CONCLUSIONS: In chronic hepatitis C, coinfection with HIV showed a tendency towards a lower response to IFN, although this did not reach statistical significance; however, none of the HIV positive patients developed cirrhosis during the follow up and this should be considered in clinical management of such patients.

Adult↗
PubMed1997

Effects of HIV seropositivity and drug abuse on cognitive function.

Fifty-eight HIV-positive drug abusers and 22 HIV-positive nondrug abusers at stages II-III and IV of the Centers for Disease Control classification were evaluated neuropsychologically. The study confirmed previous findings that drug abuse has a negative influence on cognitive function. It also emerges that seropositivity affects cognitive function, although the poor performance of group II-III patients compared to group IV may be explained by factors related to seropositivity (anxiety and panic) rather than the disease itself. It is concluded that disease-related factors probably determine cognitive performance in the earlier stages of HIV infection.

AIDS Dementia Complex↗