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Biomedical subjects

J Reynes

Publications and source records attributed to J Reynes.

At least 73 records · Page 4Linked to original sources

CD4 masking during human immunodeficiency virus type 1 infection, quantified on peripheral blood lymphocytes, is a potential marker of disease progression.

In human immunodeficiency virus type 1 (HIV-1)-infected adults, the proportion of gp120-free CD4 molecules on the surface of T lymphocytes was measured by double-epitope EIA and expressed as a CD epitope concentration ratio. In 51% of these patients (n=81), CD4 T cells showed a significant decrease (up to 100%) in the accessibility of the CD4 epitope in the D1 domain remained accessible. Of interest, a significant increase in the CD4 gp120 binding site concentration, without a change in T cell counts, was observed within 10 days after initiation of zidovudine treatment. Furthermore, CD4 masking by gp120 was associated with a poor clinical patient status. The assessment of the CD4 epitope concentration ratio is proposed as a surrogate marker of disease progression in HIV-1-infected patients.

Adult↗

Amphotericin B in a lipid emulsion for the treatment of cryptococcal meningitis in AIDS patients.

We determined the safety and efficacy of deoxycholate-amphotericin B (d-AmB) mixed with Intralipid (IL) as the initial treatment of AIDS-associated cryptococcal meningitis in a phase II, multicentre, non-comparative open study, assessing two dosages of ILd-AmB: 1 mg/kg (group A, n = 9) and 1.5 mg/kg (group B, n = 6). Patients were treated daily for 2 weeks, then three times weekly for 4 weeks. The ILd-AmB dosage was decreased due to toxicity in three patients in each group. Serum creatinine increased significantly on day 14 in group A and on day 7 in group B. Nephrotoxicity, (serum creatinine level > 165 mumol/L) was noted in two and five patients in groups A and B, respectively. Nine adverse haematological events were noted (seven cases of anaemia requiring transfusion, and two cases of neutropenia < 750/mm). Two patients had an increase in serum alkaline phosphatase. In each cohort, 15% of the infusions were associated with fever and/or chills. Successful outcome was obtained in half of the patients. We conclude that, in AIDS patients with cryptococcosis, tolerance to ILd-AmB was acceptable when the daily dosage did not exceed 1 mg/kg, but the higher 1.5 mg/kg daily dosage was associated with an unacceptable rate of nephrotoxicity. Neither of these relatively high daily dosages of ILd-AmB achieved an improved rate of successful outcomes compared with lower daily dosages of conventional d-AmB in glucose.

AIDS-Related Opportunistic Infections↗

Comparative resistance of Candida albicans clinical isolates to fluconazole and itraconazole in vitro and in vivo in a murine model.

Relationships between azole susceptibility and in vivo response to antifungal therapy in a murine model of candidiasis were investigated for Candida albicans isolates sampled from human immunodeficiency virus type 1-positive patients with oropharyngeal candidiasis. The susceptibilities of seven clinical isolates and two reference strains to fluconazole (FCZ) and itraconazole (ITZ) were determined in vitro by the broth microdilution method. Four isolates were resistant to FCZ and ITZ, two were susceptible to both azoles, and three were resistant to FCZ and susceptible to ITZ (dissociated resistance). CD1 mice were inoculated with each isolate and treated with either FCZ or ITZ (drug regimen, 5 mg/kg of body weight twice daily for 5 days). Quantitative cultures of kidneys were performed at the end of the treatment. On the other hand, the survival rates of the mice were followed daily. These two parameters were clearly correlated with in vitro susceptibility. Thus, the phenomenon of a dissociation of resistance to FCZ and ITZ may be found in vivo as well as in vitro.

Animals↗

A highly sensitive and rapid procedure for direct PCR detection of Leishmania infantum within human peripheral blood mononuclear cells.

We have developed a highly sensitive, simple and rapid procedure to detect Leishmania infantum within human macrophages. It only requires ficoll preparation of peripheral blood mononuclear cells from the patient, and their direct use for Leishmania kDNA amplification by polymerase chain reaction. Under these conditions, about one parasite can be detected in a one million human cell environment. Results, including those of a hybridization step to confirm the diagnosis specificity, are obtained with 24 h, a very short period as compared to current diagnostic methods. This procedure is of particular interest for early detection and early drug treatment of leishmaniasis, especially in the case of HIV coinfection. Furthermore, the method could be useful for monitoring the efficiency of new leishmaniasis treatments in infected patients.

Animals↗

Leishmania-human immunodeficiency virus coinfection in the Mediterranean basin: isoenzymatic characterization of 100 isolates of the Leishmania infantum complex.

Isoenzymatic characterization was done on 100 isolates obtained from visceral leishmaniasis (VL) patients coinfected with human immunodeficiency virus (HIV); isolates had been received between 1986 and 1993 at the International Leishmania Cryobank and Identification Centre in Montpellier, France. Electrophoresis was done with 15 isoenzymes using the starch gel technique combined, where appropriate, with isoelectrofocusing. Nine Leishmania infantum zymodemes were identified; L. infantum zymodeme MON-1, the most common parasite of human VL in the Mediterranean basin, was the most frequent in coinfections. It could also occasionally be responsible for localized cutaneous leishmaniasis lesions. Several dermotropic zymodemes, which were responsible for localized cutaneous leishmaniasis in immunocompetent patients, caused VL in HIV-positive patients. In addition, in 10 patients, a second isolate obtained during relapses occurring between 1.5 and 9.0 months after treatment was identical to the original isolate.

Animals↗

Fluconazole- and itraconazole-resistant Candida albicans strains from AIDS patients: multilocus enzyme electrophoresis analysis and antifungal susceptibilities.

Multilocus enzyme electrophoresis and in vitro susceptibility testing with a broth microdilution method were used to analyze Candida albicans strain diversity in four AIDS patients with recurrent oropharyngeal candidiasis who successively developed clinical resistance to fluconazole (FCZ) and itraconazole (ITZ). One to ten colonies per sample were randomly chosen from oral washings collected before the initial FCZ treatment and just before every other antifungal treatment; a total of 98 isolates were analyzed. Multilocus enzyme electrophoresis analysis revealed 14 different electrophoretic types (ETs). Statistical analysis of genetic distances showed that C. albicans isolates clustered into five subpopulations (I to V). In each subpopulation, isolates are closely related, and genetic distances between subpopulations I to IV are short. In contrast, subpopulation V, which contained isolates typed as ET8 and ET14, is strongly divergent from the others; these isolates may represent atypical C. albicans isolates. Only one patient was infected with a single strain during the course of azole therapy; for the three remaining patients, variants of the same strain and different strains were concurrently isolated. Clinical FCZ resistance was clearly correlated with in vitro data for three patients. Moreover, MICs of ITZ increased during FCZ therapy, and MICs of ITZ which were > or = 1.56 micrograms/ml were found when clinical ITZ resistance occurred; isolates from subpopulation V showed the highest MICs of ITZ. Because of the emergence of clinical ITZ resistance after clinical FCZ resistance, the feasibility of long-term azole therapy for mucosal candidiasis in AIDS patients is questioned.

Acquired Immunodeficiency Syndrome↗

Visceral leishmaniasis in HIV-infected patients in the south of France.

Between 1989 and 1993, investigations by classical parasitological procedures of 139 HIV-infected adults living in visceral leishmaniasis (VL) endemic areas showed that 10 of them (7.2%) were positive for Leishmania (by stained smears and culture). In the same period we identified 15 VL cases in patients not infected with HIV. Thus, 40% (10/25) of our VL cases were associated with HIV infection.

AIDS-Related Opportunistic Infections↗

Relationship between fluconazole sensitivity of Candida albicans isolates from HIV positive patients and serotype, adherence and CD4+ lymphocyte count.

The sensitivity of fluconazole, serotype and adherence to buccal epithelial cells of 46 Candida albicans isolates was studied in vitro. Strains were isolated from 18 HIV-positive patients with variable CD4+ lymphocyte counts who were receiving long-term fluconazole therapy. Results showed that sensitivity to fluconazole correlated with serotype. Of the sensitive isolates 81.5% were serotype A and 18.5% serotype B, whereas of the resistant isolates 37.5% were serotype A and 62.5% serotype B. Sensitivity to fluconazole also correlated with adherence capacity, resistant isolates showing slightly less adherence to buccal epithelial cells than sensitive isolates. Weakly adherent isolates represented 87% of resistant isolates and only 63% of sensitive isolates. Resistant strains were isolated in highly immunocompromised patients. All strains isolated in patients with CD4+ lymphocyte counts above 200 lymphocytes/microliters were sensitive, whereas intermediate and resistant strains were isolated in patients with counts below 200 lymphocytes/microliters. Statistical analyses showed no correlation between adherence of isolates to buccal epithelial cells and CD4+ lymphocyte counts.

AIDS-Related Opportunistic Infections↗

Spontaneous in vitro anti-human immunodeficiency virus type 1 antibody secretion by peripheral blood mononuclear cells is related to disease progression in zidovudine-treated adults.

As part of a continuous search for surrogate markers of therapeutic efficacy in AIDS, spontaneous in vitro production by peripheral blood mononuclear cells of antibody to human immunodeficiency virus type 1 (HIV-1) was investigated in 50 HIV-1-infected adults. It was independent of CD4+ cell counts, p24 antigenemia, serum beta 2-microglobulin concentration, and clinical status of the patients. The effect of zidovudine on this antibody secretion and the appearance of signs or symptoms of HIV-1 disease progression were evaluated in 20 patients over 24 weeks. Anti-HIV-1 antibody secretion decreased significantly (P = .002) as of the first month of zidovudine treatment only in the 13 HIV-1-infected patients without disease progression. This is earlier than the occurrence of variations in CD4+ cell count and serum beta 2-microglobulin concentration. These results suggest that in vitro antibody production could be a surrogate marker for evaluation of the in vivo antiretroviral efficacy of zidovudine, even in p24 antigen-negative patients.

Adult↗

[Adherence of isolated Candida albicans strains from HIV+ infected patients to buccal epithelial cells: correlation with serotype, sensitivity to fluconazole and virulence].

During infection by human immunodeficiency virus (HIV), oral pseudomembranous candidiasis frequency is high. Adherence of Candida albicans to epithelial cells constitutes one of the first step in the setting up of candidiasis. Adherence ability of Candida albicans to buccal epithelial cells (BEC) is estimated for 83 isolates. The yeasts are isolated from buccal swabs from HIV+ patients with clinical oropharyngeal candidiasis. Results show that Candida albicans ability to adhere to BEC is variable within isolates; it appears that most of the isolates are weakly adherent. In addition, adherence is not correlated with the serotype A or B of yeasts. We do not either observe any correlation between adherence capacity and sensibility of yeasts to fluconazole. Moreover, no correlation is observed between a group of 13 genetically identical isolates (analysed on 21 loci with isoenzymes method) and their adherence to BEC. Finally, Candida albicans virulence, which is studied in vivo on intravenously infected mouse model, does not seem to be correlated with capacity of each yeast to adhere on BEC in vitro.

AIDS-Related Opportunistic Infections↗

[Treatment with clarithromycin of 173 HIV+ patients with disseminated Mycobacterium avium intracellulare infection].

No treatment was established for disseminated M. avium intracellulare (MAC) infection, a common disease of end stage of AIDS. An open study was conducted to assess in 173 AIDS patients, the activity of clarithromycin. Initial bacteriologic eradication from blood was observed in 136/147 evaluable patients (93%). Acquired resistance to clarithromycin associated with relapse appeared to develop after 2 to 7 months of drug treatment in 31/136 patients with initial success. Early bacteriological relapse was associated with clinical deterioration. Side effects of drug treatment were elevated liver enzymes (26%) and impaired hearing (4%). Side effects conducted to stop treatment in 14 cases (8%) to modified treatment in 8 cases (5%). Our study gave new argues for activity of clarithromycin in disseminated MAC infection.

AIDS-Related Opportunistic Infections↗

Trimethoprim-sulfamethoxazole versus aerosolized pentamidine for primary prophylaxis of Pneumocystis carinii pneumonia: a prospective, randomized, controlled clinical trial. LFPMI Study Group. Ligue Française de Prévention des Maladies Infectieuses.

The objective was to compare the efficacy and tolerance of monthly aerosolized pentamidine versus trimethoprim-sulfamethoxazole (TMP-SMX) to prevent the first episode of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus (HIV)-infected patients. In an open, prospective, randomized multicentric clinical trial, HIV-infected patients (n = 214) with CD4 cell counts < 200/mm3 or 20% without a history of PCP or cerebral toxoplasmosis were randomized to receive for at least 2 years aerosolized pentamidine (300 mg monthly) or low-dose daily TMP-SMX (400-80 mg). The mean follow-up was 578 days. The two groups (except for gender) were homogeneous for age, risk group for HIV infection, initial CD4+ lymphocyte count, and mean follow-up. The PCP rate per year of observation using an intent-to-treat analysis was 3.1% and 1.3% in the groups treated with pentamidine and TMP-SMX, respectively (p > 0.05). Moderate or severe clinical and biological side effects were observed in five patients on pentamidine and 33 on TMP-SMX (p < 0.05). Nineteen episodes of cerebral toxoplasmosis were diagnosed during the study. The analysis showed no significant difference in time of development of toxoplasmosis, but only one patient was actually treated with TMP-SMX. Survival was not significantly different in the two groups. Low-dose daily TMP-SMX or monthly aerosolized pentamidine effectively prevented a first episode of PCP in HIV-infected patients, but aerosolized pentamidine was better tolerated. However, TMP-SMX is less costly and should have a preventive effect for toxoplasmosis.

AIDS-Related Opportunistic Infections↗

The yeast Candida albicans has a clonal mode of reproduction in a population of infected human immunodeficiency virus-positive patients.

To ascertain the population structure of Candida albicans, we have carried out a multilocus enzyme electrophoresis study based on the analysis of 21 gene loci. We have thus characterized 55 strains isolated one each from 55 human immunodeficiency virus-positive patients. There is considerable polymorphism among the strains. A population-genetic analysis indicates that the two fundamental consequences of sexual reproduction (i.e., segregation and recombination) are apparently absent in this population of C. albicans. The population structure of C. albicans appears to be clonal, a state of affairs that has important medical and biological consequences.

Candida albicans↗

In-vitro synthesis of antibodies to Toxoplasma gondii by lymphocytes from HIV-1-infected patients.

Toxoplasma-specific in-vitro antibody production by peripheral blood lymphocytes (PBL) was investigated in 124 adults infected with human immunodeficiency virus (HIV-1). PBL from 20 of 21 patients with cerebral toxoplasmosis showed spontaneous in-vitro secretion of antibodies to Toxoplasma gondii antigens. Among 103 HIV-1-infected patients without signs or symptoms of toxoplasmosis, PBL from 19 produced toxoplasma-specific antibodies in vitro; 5 of these patients, who discontinued prophylaxis for toxoplasmic encephalitis, showed in-vitro antibody production 3-15 months before the diagnosis of toxoplasmic encephalitis. In-vitro production of toxoplasma-specific antibodies could improve the diagnosis of toxoplasmic encephalitis in HIV-1-infected patients.

AIDS-Related Opportunistic Infections↗

Comparative humoral responses to human immunodeficiency virus type 1-p24gag linear B-cell epitopes among individuals showing atypical western immunoblotting reactions and implications for diagnosis.

Serum specimens from 25 individuals with an isolated human immunodeficiency virus type 1 (HIV-1) core antigen reactivity in a Western immunoblot test were examined for their reactivities with HIV-1 virions, control cellular antigens, HIV-1-Bru p24gag recombinant protein (p24gag), and a panel of 22 p24gag-derived peptides. The results were as follows: (i) serum specimens from eight HIV-1-uninfected subjects did bind to virions but failed to bind to p24gag; (ii) sera from 13 HIV-1-uninfected subjects and from one HIV-2-infected patient reacted with HIV-1 virions and p24gag but failed to bind to any of the peptides expressing major p24gag epitopes, and (iii) 3 serum specimens obtained from one neonate carrying anti-HIV-1 maternal antibody and from two HIV-1-infected subjects who had seroconverted during the study reacted with HIV-1 virions, p24gag, and one or more peptides containing the major p24gag epitopes. Our data suggest that the combination of p24gag and appropriate peptides could be useful for resolution when atypical Western immunoblot results are encountered.

Amino Acid Sequence↗

[Electromyographic, histoenzymologic and immunocytochemical aspects of affected muscles in HIV infection. Observations of five cases].

In 5 acquired-immunodeficiency syndrome (AIDS) cases without peripheral neuropathy, we observed myogen clinical signs (diffuse amyotrophy of lower limbs or cramps) or an isolated increase in seric enzyme (LDH, CK). EMG abnormalities were observed in all cases: spontaneous activities (fibrillations and positive sharp waves) in 5 cases, myogenic signs in 2 case. Muscular biopsies were normal in 3 cases and showed myopathic changes in 1 case and polymyositis in another case. Antidystrophin and antilaminin antibodies reactions were altered in 1 case. The spontaneous activities together with these modifications could be in favour of a lesion at the membrane level.

Acquired Immunodeficiency Syndrome↗