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Biomedical subjects

L Cotte

Publications and source records attributed to L Cotte.

At least 37 records · Page 2Linked to original sources
PubMed1997

Potential efficacy of fumagillin in intestinal microsporidiosis due to Enterocytozoon bieneusi in patients with HIV infection: results of a drug screening study. The French Microsporidiosis Study Group.

OBJECTIVE: Intestinal microsporidiosis due to Enterocytozoon bieneusi is a frequent cause of chronic diarrhoea in patients with HIV infection for which there is no available therapy. This study was designed to search for a drug with activity against this organism. DESIGN: Prospective open-labelled Phase II multicentre study. SETTING: University hospitals. PATIENTS: Sixty HIV-infected men with intestinal E. bieneusi infection. INTERVENTIONS: Ten drug regimens were consecutively tested orally for 3 weeks: albendazole plus metronidazole, sulphadiazine plus pyrimethamine, atovaquone, doxycycline plus nifuroxazide, itraconazole, flubendazole, chloroquine, paromomycin, sparfloxacin and fumagillin. Nine evaluable patients per regimen were required, but each patient could be enrolled up to three times in the study. OUTCOME MEASURE: Efficacy was assessed primarily by the clearance of E. bieneusi from stools and intestinal biopsies. The safety of each regimen was also assessed. RESULTS: Only purified fumagillin was able to clear E. bieneusi from stools as well as intestinal biopsies, whereas all other regimens failed to show antiparasitic efficacy. However, only four patients received fumagillin because of drug-induced thrombocytopenia. The four patients who received fumagillin remained free of E. bieneusi infection after a mean follow-up of 10 months. CONCLUSION: Eradication of E. bieneusi from the intestinal tract of patients with HIV infection and persistent immunosuppression is an achievable goal. Our study allowed the identification of oral fumagillin as a potential treatment for intestinal microsporidiosis due to E. bieneusi.

AIDS-Related Opportunistic Infections↗
PubMed1997

Rapid detection of Pneumocystis carinii in bronchoalveolar lavage specimens from human immunodeficiency virus-infected patients: use of a simple DNA extraction procedure and nested PCR.

We report on the development of a rapid nested PCR protocol for the detection of Pneumocystis carinii DNA in bronchoalveolar lavage (BAL) specimens in which the protocol included the use of a commercially available DNA extraction kit (GeneReleaser). GeneReleaser enabled us to obtain amplification-ready DNA within 20 min without requiring the purification of the DNA. The nested PCR was performed with the primers pAZ102-E, pAZ102-H, and pAZ102-L2 (A. E. Wakefield, F. J. Pixley, S. Banerji, K. Sinclair, R. F. Miller, E. R. Moxon, and J. M. Hopkin, Lancet 336:451-453, 1990.). Results were obtained in about 4 h with the adoption of denaturation, annealing, and extension steps shortened to 20 seconds. The sensitivity of the nested PCR was tested with a P. carinii cyst suspension and was found to be less than one cyst (one to eight nuclei). The detection limit was the same with the use of GeneReleaser or proteinase K-phenol chloroform for DNA extraction. The nested PCR assay was prospectively compared with staining with Giemsa and methenamine silver stains for the detection of P. carinii in 127 BAL samples from 105 human immunodeficiency virus-infected patients investigated for acute respiratory illness. Twenty-five BAL specimens (20%) were positive by staining and the nested PCR and 25 (20%) were negative by staining and positive by the nested PCR. These 25 BAL specimens with conflicting results were obtained from 23 patients, 82% of whom were receiving prophylactic therapy against P. carinii pneumonia (PCP). Only two patients were diagnosed with possible PCP. The final diagnosis was not PCP for 20 patients who were considered to be colonized or to have a low level of infection. This colonization is not of clinical importance but is of epidemiological importance. Our rapid, simple, and sensitive amplification protocol may be performed in clinical laboratories for the routine diagnosis of PCP with BAL specimens.

AIDS-Related Opportunistic Infections↗
PubMed1997

Development of a reverse transcriptase PCR-enzyme-linked immunosorbent assay for quantification of human immunodeficiency virus type 1 RNA in plasma: comparison with commercial quantitative assays.

A quantitative reverse transcriptase PCR assay with automated detection by nonradioactive hybridization was developed for the determination of human immunodeficiency virus (HIV) type 1 RNA levels. This assay is based on the use of an external standard curve with an internal standard. The accuracy of quantification was verified by comparison with reference commercial tests, the Chiron branched-DNA and Roche AMPLICOR HIV MONITOR assays. This assay was able to quantify viremia in patients with CD4 cell numbers below and above 500/mm3 and to quantify some HIV strains which could not be titrated by the MONITOR assay.

DNA Primers↗
PubMed1996

Predictive value of HIV-1 RNA detection in plasma by branched DNA assay during long-term zidovudine therapy.

The predictive value of human immunodeficiency virus type 1 (HIV-1) RNA detection in plasma using branched DNA assay was studied in a subgroup of 36 asymptomatic HIV-1-infected patients enrolled in a multicenter, double-blind, randomized study. Patients were randomized to receive either zidovudine (AZT) 1 g/day or placebo and were monitored for a mean time of 61 months. HIV-1 RNA was detected in plasma using branched DNA assay at months 0, 6, 12, 24, and 36. HIV-1 RNA was detected at levels of > or = 10(4) RNA eq/ml (eq/ml) in 8.3% of the patients at baseline, and this percentage increased during the first two years in the placebo group only. The detection rate of HIV-1 RNA at three years was 50% in both the AZT and the placebo groups. HIV-1 RNA levels ranged from 10(4) to 478 x 10(3) RNA eq/ml. HIV-1 RNA was detected at levels of > or = 10(4) eq/ml a mean time of 19 +/- 13 months before progression to AIDS in 76.5% of progressing patients. In a multivariate analysis including baseline CD4+ count, the initial randomization group, HIV-1 RNA detection in plasma, and detection of p24 antigenemia during the first three years of follow-up, the best independent predictors of progression to AIDS at five years and the best independent predictors of death at five years were HIV-1 RNA detection in plasma and p24 antigenemia.

Acquired Immunodeficiency Syndrome↗
PubMed1996

In situ detection of human cytomegalovirus DNA in gastrointestinal biopsies from AIDS patients by means of various PCR-derived methods.

The development of new in situ assessment of HCMV disease on endoscopical gastrointestinal biopsies from AIDS patients is described and compared with the viral load measured by semiquantitative solution-phase PCR (SQ-PCR). Ten biopsies were examined by viral isolation, standard histology, in situ hybridization (ISH), in situ PCR-hybridization (PCR-ISH) and SQ-PCR, using the same target sequence. The methods developed for in situ HCMV detection were HCMV primers, the plasmid pCMV 406-S, a vector-free-digoxigenin-labelled HCMV-362 probe and the pSK + MCS nonsense probe. Paraffin-embedded MRC5 cells, either HCMV-infected or uninfected served as controls of specificity for ISH. beta-Actin primers were designed as markers of DNA integrity. Computerized models of the PCR, solution-phase and in situ PCR on formalin-fixed DNA indicated that HCMV and beta-actin primers were efficient and specific. Nine biopsies were negative for HCMV by histology and virus isolation. SQ-PCR revealed 80,000; 80 and < 80 HCMV genomic equivalents in 6, 2 and 2 biopsies, respectively. In 8 biopsies, both ISH and PCR-ISH identified positive nuclei in the intestinal epithelium, with sparing of the lamina propria. This indicates that an improvement in in situ methods can help the timely diagnosis of HCMV infection. Direct in situ PCR with beta-actin primers showed a positive signal in all the nuclei in the tissue sections, whereas omission of Taq polymerase resulted in an absence of signal, implying optimal in situ PCR. The data suggest an early-stage reactivation of HCMV, possibly harboured in the intestinal epithelium.

AIDS-Related Opportunistic Infections↗
PubMed1996

Cytomegalovirus DNA level on biopsy specimens during treatment of cytomegalovirus gastrointestinal disease.

BACKGROUND & AIMS: There is no clear and point for the response to treatment of gastrointestinal human cytomegalovirus (HCMV) disease. HCMV-DNA quantitation on gastrointestinal biopsy specimens has proven its value for the diagnosis of gastrointestinal HCMV disease in patients with acquired immunodeficiency syndrome (AIDS). The aim was to study HCMV-DNA levels on gastrointestinal biopsy specimens during the treatment of gastrointestinal HCMV disease. METHODS: HCMV-DATA quantitation was performed using two different polymerase chain reaction assays on 90 biopsy specimens obtained before anti-HCMV therapy, during the induction phase, or during maintenance therapy for gastrointestinal HCMV disease in 21 patients with AIDS. RESULTS: HCMV-DNA was detected on all the biopsy specimens ranging from 9 to > or = 80,000 Eq/0.1 microgram DNA. Pretherapeutic mean level was 69,000 +/- 27,000 Eq/0.1 microgram DNA. Induction therapy was followed by a mean decrease of 1.7 +/- 1.3 log10 Eq/0.1 microgram DNA. HCMV-DNA levels decreased during induction therapy to < 1000 Eq/0.1 microgram DNA in 60% of patients but remained > 80,000 Eq/0.1 microgram DNA in 20% of patients. Relapse occurred in all the patients in a mean time of 100 days. HCMV-DNA level at the end of the induction phase seems to influence the time to relapse. CONCLUSIONS: Quantitation of HCMV-DNA on gastrointestinal biopsy specimens seems to be useful for monitoring gastrointestinal HCMV disease in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Enterocytozoon bieneusi as a cause of chronic diarrhea in a heart-lung transplant recipient who was seronegative for human immunodeficiency virus.

Enterocytozoon bieneusi is a major cause of chronic diarrhea and malabsorption in patients with AIDS. We report what we believe is the first case of intestinal infection due to E. bieneusi in a heart-lung transplant recipient who was seronegative for human immunodeficiency virus (HIV). The clinical presentation and the evolution of the disease were identical to those usually observed in patients with AIDS and included diarrhea, massive weight loss, and persistent infection despite treatment with albendazole. E. bieneusi was identified in the patient's duodenal mucosa by electron microscopy. No other etiologic agent was detected. We conclude that E. bieneusi may be responsible for serious intestinal infections in patients whose immunosuppression is not related to HIV.

Animals↗
PubMed1994

Paromomycin: an effective treatment for cryptosporidial diarrhea in patients with AIDS.

Cryptosporidiosis is a common cause of diarrhea in patients with AIDS but remains one of the most challenging AIDS-related conditions to treat. We therefore carried out an open, uncontrolled, prospective study to evaluate the efficacy of oral paromomycin for the treatment of chronic diarrhea due to Cryptosporidium in 24 successive patients infected with human immunodeficiency virus. Twenty-two of the 24 patients responded clinically, with complete remission occurring in 18 cases and marked reduction of the diarrhea occurring in four. Clearance of cryptosporidia from stools and/or intestinal biopsy specimens occurred within 2-4 weeks. Furthermore, all 18 patients who achieved complete remission gained weight. Ten patients relapsed either during administration of maintenance therapy or after discontinuation of treatment, but diarrhea resolved again after increasing or restarting paromomycin therapy in all but two. Paromomycin appeared to be an active and well-tolerated treatment for cryptosporidiosis in patients with AIDS. Efficacy is dose-related, and continuous maintenance therapy is required to prevent relapses. These data suggest that paromomycin might be given as first-line therapy in AIDS-related cryptosporidiosis, but this should be confirmed by the findings of a controlled, randomized trial.

AIDS-Related Opportunistic Infections↗
PubMed1994

Fulminant hepatitis with severe lactate acidosis in HIV-infected patients on didanosine therapy.

We report two cases of fulminant hepatic failure in HIV-1-infected patients treated with didanosine (ddI). Clinical manifestations including vomiting, diarrhoea and dyspnoea were identical in both cases. Biological data mainly revealed hepatic failure and lactic acidosis. Histological examination of liver biopsies showed diffuse microvesicular steatosis. The outcome was fatal in both patients. The only comparable case previously reported (Lai et al., 1991) showed close similarities in the clinical, biological and histological manifestations with microvesicular steatosis. This prompted us to suspect that ddI might be responsible for fulminant hepatitis in all three AIDS patients. This toxic effect may be added to the list of potential adverse events occurring during ddI therapy.

AIDS-Related Opportunistic Infections↗
PubMed1993

Clarithromycin and other antimicrobial agents in the treatment of disseminated Mycobacterium avium infections in patients with acquired immunodeficiency syndrome.

BACKGROUND: Disseminated infection with Mycobacterium avium is common with late-stage acquired immunodeficiency syndrome (AIDS), and no antimicrobial agent has been found to be clearly effective. METHODS: A multicenter open trial was conducted to assess the antimicrobial activity and clinical efficacy of clarithromycin--a new macrolide antibiotic--against disseminated M avium in 77 patients with late-stage AIDS. Blood cultures were taken at baseline and during treatment; side effects were also evaluated. RESULTS: Mycobacterium avium was eradicated from blood cultures in 11 (63%) of 16 evaluable patients receiving daily doses or 500 or 1000 mg, (n = 21) and in 45 of 46 (98%) of those receiving 1500 or 2000 mg (n = 56). Eradication after 2 months was influenced by continuity of drug treatment; 36 of 42 patients with no relapse had received continuous treatment vs six of 14 patients whose drug treatment had been stopped for 7 days or longer. After 2 to 7 months of treatment, acquired resistance associated with relapse was observed. Drug side effects were elevated liver enzyme levels (26%) and impaired hearing (4%). Concomitant AIDS drugs had no favorable effect on outcome and may have worsened liver toxicity. CONCLUSIONS: Clarithromycin has bacteriologic efficacy against M avium infection in late-stage AIDS, although drug resistance eventually develops. Further studies are needed to investigate safe, effective concomitant drugs.

AIDS-Related Opportunistic Infections↗