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Biomedical subjects

C Perronne

Publications and source records attributed to C Perronne.

At least 55 records · Page 3Linked to original sources
PubMed1996

Mycobacterium avium complex infection in mice: lack of exacerbation after LP-BM5 murine leukemia virus infection.

The murine leukemia virus LP-BM5 has been used to reproduce the model of murine AIDS in order to evaluate the course of infection with the MO-1 strain of Mycobacterium avium complex (MAC). LP-BM5 was inoculated in C57BL/6 mice by intravenous (i.v.) injection either 8 weeks before an i.v. challenge with 10(3) or 10(6) CFU of MAC (coinfection 1) or 10 days after an i.v. challenge with 10(3) CFU of MAC (coinfection 2). During coinfection 2 experiments, the phenotypic alterations in blood lymphocyte subsets were analyzed. During coinfection 1, LP-BM5 infection tended to decrease the mycobacterial growth, with the difference reaching statistical significance for the lower inoculum (10(3) CFU of MAC) (P<0.001). During coinfection 2, LP-BM5 did not exacerbate MAC infection except in the spleen, at day 90 after LP-BM5 challenge (P<0.001). LP-BM5 infection and the LP-BM5-MAC coinfection increased the numbers of activated CD4+ lymphocytes (CD4+ Ly6AE+) (P<0.001), activated CD8+ lymphocytes (CD8+ Ly6AE+) (P<0.001), and activated B lymphocytes (Ly5+ Ly6AE+) (P<0.001). This activation of T lymphocytes could explain the lack of exacerbation of MAC infection and even the trend to a lower level of MAC infection. Thus, this model of retroviral infection of mice does not seem to be a reliable model of immunodepression for the study of MAC infection and its treatments.

Animals↗
PubMed1996

Pulmonary capillary blood volume in patients with probable pulmonary Kaposi's sarcoma.

BACKGROUND: An increase in pulmonary capillary blood volume secondary to angiogenesis has been described in Kaposi's sarcoma. The value of the pulmonary capillary blood volume as an early marker of pulmonary Kaposi's sarcoma was evaluated. METHODS: In a prospective study 45 HIV positive patients (nine asymptomatic for Kaposi's sarcoma, 29 with cutaneous or mucocutaneous Kaposi's sarcoma, and seven with pulmonary Kaposi's sarcoma), underwent pulmonary function tests and determination of transfer capacity for carbon monoxide (TLCO) with its components, pulmonary capillary volume and membrane factor. RESULTS: Total lung capacity (TLC), TLCO, and its components were similar in the three groups. TLCO was normal in patients with pulmonary Kaposi's sarcoma and no changes in membrane factor or pulmonary capillary volume were observed. CONCLUSION: Pulmonary function tests and pulmonary capillary volume alone are not useful for identifying patients with pulmonary Kaposi's sarcoma.

Adult↗
PubMed1995

[Mycobacterial infections in AIDS].

Mycobacterial infections are the main cause of bacterial infections during HIV infection. The HIV infection epidemic contributed to the worldwide resurgence of the tuberculous endemic. The clinical presentation of tuberculosis is often atypical and extrapulmonary. The general guidelines for treatment are not modified, but HIV infection often worsens the tolerance of treatment. A poor compliance to treatment is the main cause of relapse or of selection of resistant mutants. The two main points for the control of tuberculosis in the era of HIV are a free access of patients to antituberculosis drugs, and a surveillance of the compliance until treatment is completed. Atypical mycobacteria, mainly represented by Mycobacterium avium, are bacteria from the environment, poorly virulent, responsible for infections occurring late in the course of AIDS. Current treatments use combinations including clarithromycin.

AIDS-Related Opportunistic Infections↗
PubMed1995

Analysis of the immunological humoral response to Mycobacterium tuberculosis glycolipid antigens (DAT, PGLTb1) for diagnosis of tuberculosis in HIV-seropositive and -seronegative patients.

Using an enzyme immunoassay (EIA) test, the concentrations of IgG antibodies against 2,3 diacyl trehalose (DAT) and phenolic glycolipid Tb1 (PGLTb1) were measured in the sera of 153 patients with active tuberculosis, 50 of whom were coinfected with HIV, and in the sera of 152 healthy blood donors, 149 asymptomatic HIV-seropositive patients, 12 HIV-seronegative patients with conditions simulating tuberculosis, 23 HIV-seropositive patients with disseminated infection caused by mycobacteria other than tuberculosis and 24 HIV-seropositive patients with pulmonary disease from whom mycobacteria was not isolated in culture. A slightly lower percentage (74%) of the HIV-seropositive than the HIV-seronegative (77%) tuberculosis patients were positive for anti-DAT and anti-PGLTb1 IgG antibodies, with a specificity ranging from 91 to 95%. There was no significant difference between EIA sensitivity in smear-positive and smear-negative patients with pulmonary tuberculosis for all HIV immune statuses and sites of disease (pulmonary vs. extrapulmonary). In HIV-seropositive patients, however, sensitivity was always lower for disseminated tuberculosis than for localized tuberculosis. Combining data for both the smear test and the EIA maximized sensitivity. The main value of the EIA test could be to provide early complementary information by antibody detection in patients with tuberculosis, particularly those with a negative smear test.

Adult↗
PubMed1995

[Multidrug-resistant tuberculosis. Epidemiology, treatment, prevention and diagnostic research].

The recent augmentation of the prevalence of multidrug resistant (MDR) tuberculosis is related to the high incidence of tuberculosis in HIV infected people, especially in those with low social status and no medical care; several nosocomial epidemics of MDR tuberculosis were observed in American and European institutions where HIV-infected persons were hospitalized; these MDR tuberculosis were associated with a high mortality-rate and frequent nosocomial transmission to immunocompromised contacts and care workers. The rapid institution of an adequate treatment with ancient antituberculosis agents (cycloserin, capreomycin, aminoglycosides) and/or new drugs (rifabutine, ofloxacin, sparfloxacin, etc) is necessary to avoid mortality and to diminish transmission. Prevention of MDR tuberculosis transmission is very important: patient isolation, adequate and prolonged therapy, better detection of resistance with gene-amplification methods (PCR) which are under investigation.

Comorbidity↗
PubMed1995

Use of normal C57BL/6 mice with established Mycobacterium avium infections as an alternative model for evaluation of antibiotic activity.

Several murine models have been used to evaluate the activities of antimicrobial agents against Mycobacterium avium infection. The main model used is the beige mouse model, but beige mice are expensive and not easily available. Thus, we developed a model of infection in wild C57BL/6 mice. The drugs that exhibited some activity in a previous model of early infection were evaluated in a new model of established infection. Sparfloxacin (50 mg/kg of body weight), ethambutol (50 mg/kg), minocycline (25 mg/kg), and the inhibitor of the cortisol receptors RU-40555 (100 mg/kg) were compared with clarithromycin (50 mg/kg). Treatments were started 5 weeks after the inoculation and were continued for 21 days. Sparfloxacin and RU-40555, which exhibited a moderate activity in the model of early infection, were not effective in this model of established infection. Clarithromycin and combinations with clarithromycin kept their activities against M. avium infection, both in the spleen and in lungs. The present model of established infection of normal C57BL/6 mice is more relevant than the model of early infection for a stringent evaluation of drugs.

Animals↗
PubMed1995

Activities of roxithromycin against Mycobacterium avium infections in human macrophages and C57BL/6 mice.

The activity of roxithromycin against three clinical isolates of Mycobacterium avium was compared with that of clarithromycin both in a model of infection of human monocyte-derived macrophages and in a model of established infection of C57BL/6 mice. In the cell culture model, roxithromycin and clarithromycin were bactericidal for strains MO-1 and N-92159 and bacteriostatic for strain N-93043. For the three strains, the differences between the intracellular activities of roxithromycin and clarithromycin were not singificant after 7 days of treatment. Mice were infected with the MO-1 strain. Drugs were given by gavage at a dosage of 200 mg/kg of body weight 6 days per week for 16 weeks starting 5 weeks after infection. At the end of treatment, clarithromycin was more effective than roxithromycin in lungs; roxithromycin was as effective as clarithromycin in spleens. Thus, the activity of roxithromycin was comparable to that of clarithromycin both in vitro and in vivo.

Animals↗
PubMed1995

Pentamidine-induced derangements of glucose homeostasis. Determinant roles of renal failure and drug accumulation. A study of 128 patients.

OBJECTIVE: To assess the prevalence, presentation, and risk factors of pentamidine-induced dysglycemia. RESEARCH DESIGN AND METHODS: Blood glucose values were screened in 244 consecutive immunocompromised patients with Pneumocystis carinii pneumonia: 116 being treated with cotrimoxazole and 128 others with pentamidine. RESULTS: Two cotrimoxazole patients developed diabetes as a result of necrotizing pancreatitis (1.7%); the others remained euglycemic. Forty-eight pentamidine-treated patients (38.5%) developed severe glucose homeostasis disorders: hypoglycemia in 7, hypoglycemia and then diabetes in 18, and diabetes alone in 23 (P < 0.001 vs. the cotrimoxazole group). Hypoglycemia was early, sudden, often recurrent, and life-threatening, associated with inappropriately high insulin levels in plasma; the B-cell response to stimuli was poor. Of the 41 diabetic patients, 26 required insulin therapy; their plasma C-peptide levels were lower than normal, and the B-cell secretory responses to stimuli were poor. Islet cell antibodies, insulin antibodies, and insulitis were not detected. The pentamidine-treated dysglycemic patients differed from their euglycemic counterparts by higher pentamidine doses (P < 0.001), higher plasma creatinine levels (P < 0.001), and more severe anoxia (P < 0.05) and shock (P < 0.001). Most of them had received pentamidine mesylate parenterally (n = 36; 75%); six others received the isethionate salt and six exclusively pentamidine aerosols. CONCLUSIONS: Pentamidine-induced dysglycemic accidents are primarily due to inappropriate insulin release and toxicity to the islet B-cells. Drug accumulation due to excessive doses, iterative courses, and/or renal impairment is the determining risk factor.

AIDS-Related Opportunistic Infections↗
PubMed1995

Mefloquine-associated hypoglycaemia in a cachectic AIDS patient.

Quinine and its isomer quinidine are well-known causes of iatrogenic hypoglycaemia, due to excessive insulin secretion. The situation is less clear regarding other anti-malarial quinine analogues. In particular, this adverse effect has never been described with mefloquine (Lariam). We report a case of hypoglycaemia after mefloquine therapy (1,500 mg over two days) for severe gastrointestinal cryptosporidiasis in a cachectic AIDS patient with protracted diarrhoea. Blood glucose levels, which were normal before treatment, dropped to 2.3 mmol/l within a few hours and were corrected by i.v. glucose infusion. Hypoglycaemia did not recur despite continued treatment. Rat islets of Langerhans exposed to mefloquine in vitro (10(-8) mol/l to 10(-3) mol/l) secreted significantly more insulin than control islets (up to 980 +/- 180 microU/ml/5 islets incubated with mefloquine 10(-3) mol/l, vs 20 +/- 4 microU/ml/5 untreated islets). Mechanisms and triggering factors of hypoglycaemia induced by mefloquine and some other anti-malarial quinine analogues are discussed. Clinicians who manage cachectic patients, particularly those with protracted diarrhoea and/or receiving anti-malarial drugs including mefloquine, should be aware of the risk of severe hypoglycaemia.

Acquired Immunodeficiency Syndrome↗
PubMed1995

[Genetic diagnosis of mycobacterium infections by polymerase chain reaction (PCR)].

Diagnosis is often difficult for mycobacteria because of the limitations of both direct microscopy and cell culture. Polymerase chain reaction (PCR), widely developed in microbiology, could provide major progress in the diagnosis of tuberculosis and atypical mycrobacterial diseases. Sensitivity rarely exceeds 80% and can be lower than 60% compared with traditional culture techniques. The specificity of tuberculosis PCR is rarely better than 97% so that the positive predictive value varies from 5 to 75% depending on the incidence of tuberculosis in the tested population (from 0.2 to 10%). The sensitivity of PCR compared with traditional culture varies from 2 to 90% depending on the laboratory. The proportion of false negative usually varies from 3 to 20%. Reliability should be improved with standardized simplified techniques, but quality control remains essential to validate the method in each laboratory. Current management strategies cannot be developed or changed solely on the grounds of PCR results.

Bacteriological Techniques↗
PubMed1995

[Azithromycin and Mycobacterium avium infection].

Mycobacterium avium infection is a frequent complication during the late stage of AIDS. M. avium is resistant or poorly susceptible to classical antituberculosis drugs. Some new macrolide antibiotics such as clarithromycin or azithromycin are bactericidal against M. avium, and their use has dramatically improved the prognosis of this infection. In vitro, azithromycin has MICs against M. avium ranging from 4 to 64 MIC50 being 16 mg/l and a MIC90 being 32 mg/l. Despite low concentrations in serum, close to 0.4 mg/l, very high intracellular concentrations of azithromycin, above the MIC, may be achieved. Azithromycin is active in vitro in the model of macrophage infection. Furthermore, azithromycin is active against murine experimental infection with M. avium. Clinical studies conducted among patients with AIDS have shown that azithromycin was active against disseminated M. avium infection, with a dose of 600 mg/d. Ongoing studies are designed to better determine the ideal dose, to compare its activity with that of clarithromycin and to determine the antibiotics that could be combined to prevent the selection of resistant mutants. Other ongoing studies are evaluating the efficacy of azithromycin for the chemoprophylaxis of M. avium infection in HIV infected patients with a CD4T lymphocyte concentration lower than 100/mm3.

AIDS-Related Opportunistic Infections↗
PubMed1994

[Association of tuberculosis and HIV infection].

Eight million people contract tuberculosis every year, 95% of them in developing countries, and one-third of the world's population is infected with Mycobacterium tuberculosis. Annually, tuberculosis causes three million deaths (in Africa 26% of the avoidable deaths). The main cause of dissemination is the absence of early diagnosis and insufficient treatment. Today, 3% of the new cases of tuberculosis are related to infection with the human immunodeficiency virus (HIV), a proportion which is rising rapidly. HIV infection does not change the classic rules of treatment; rifampicin, isoniazid, ethambutol and pyrazinamide for 2 months followed by at least 4 more months with a two-drug regimen (rifampicin and isoniazid). No-compliance is the major cause of recurrence, together with the risk of infection with another strain of M. tuberculosis. Certain authors suggest that in Africa, due to poor compliance and the lack of a sufficient provision of major antituberculous agents, treatment should be continued for life in HIV positive patients. Others propose chemotherapy for an HIV infected patients who are healthy carriers of M. tuberculosis. The risk of selecting mutant strains could be avoided by limiting prophylaxis to non-febrile patients. Nevertheless, the long-term effect of generalized chemoprophylaxis on the epidemiology of resistant strains is unknown. The only method of screening for healthy carriers is the tuberculin skin test but interpretation is complicated by prior BCG vaccination and now by HIV infection. There are two crucial steps required to control tuberculosis in this era of the tuberculosis-HIV partnership. First, patients should have easy and cost-free access to antituberculous drugs and second, compliance must be improved. Certain barriers have been lifted, including the requirement of patient identification to obtain free drugs. Hospital staffs must renew their efforts and attempt to follow-up their patients to assure compliance after discharge. All these measures will be difficult to implement but are the price we must pay to eradicate a new rise in the incidence of tuberculosis and the risk of multidrug-resistant strains. The only alternative may well be a return to pre-antibiotic days.

AIDS-Related Opportunistic Infections↗
PubMed1994

Empiric antituberculosis treatment: benefits for earlier diagnosis and treatment of tuberculosis.

SETTING: Tuberculosis may be diagnosed too late, especially in HIV-infected patients, with consequences on bacillus transmission and survival. Empiric antibuberculosis treatment (EATT) may be started before diagnosis of tuberculosis is confirmed. As rifampicin is a broad spectrum antibiotic, EATT including rifampicin may be effective in infections other than tuberculosis, leading to misdiagnosis. OBJECTIVE: To define the efficiency criteria of EATT with or without rifampicin. DESIGN: Between 1988 and 1991, 20 febrile patients with suspected tuberculosis (including 15 who were HIV-positive) were started on EATT in the absence of bacteriological or histological proof of tuberculosis. 10 patients (50%) received a 4-drug non-specific EATT including rifampicin, isoniazid, pyrazinamide and ethambutol, and 10 (50%), received a 3-drug specific EATT without rifampicin. RESULTS: In 10 patients (50%), the diagnosis of tuberculosis was confirmed by positive cultures within a mean of 32 days (15-57 days) after the beginning of EATT (group TB 1). Of the 10 patients whose cultures remained negative, 4 (20%) became afebrile and showed improvement under EATT (group TB 2), and 6 (30%) remained febrile and did not improve (group No TB). Patients from groups TB 1 and TB 2 became afebrile within a mean of 11 days (1-54 days). This delay was not different between patients receiving specific or non-specific EATT. In patients receiving specific EATT, rifampicin was added to the initial 3-drug treatment after resolution of fever. CONCLUSION: EATT appears to be a useful method for rapid presumptive diagnosis and treatment of tuberculosis.

AIDS-Related Opportunistic Infections↗
PubMed1994

Chloroquine does not enhance the activity of clarithromycin against multiplication of Mycobacterium avium within human macrophages.

SETTING: Chloroquine, an alkalinizing lysosomotropic agent, enhances the intracellular activity of antibiotics against Mycobacterium tuberculosis or Coxiella burnetii. OBJECTIVE: To determine if chloroquine modifies the activity of clarithromycin, less effective at acidic pH, against intracellular Mycobacterium avium. DESIGN: The activity of clarithromycin (4 micrograms/ml) against the MO-1 strain of M. avium was evaluated within human macrophages in presence of chloroquine (5 micrograms/ml). The minimal inhibitory concentration of clarithromycin for the strain was 2 micrograms/ml. RESULTS: While clarithromycin alone did decrease the intracellular infection at day 7 of culture (P < 0.01), chloroquine alone did not impede the intracellular growth of M. avium, and did not enhance the activity of clarithromycin. CONCLUSION: Chloroquine should not improve clarithromycin treatment against M. avium infection.

Cells, Cultured↗
PubMed1994

Pyogenic and tuberculous spondylodiskitis (vertebral osteomyelitis) in 80 adult patients.

Bacterial spondylodiskitis--i.e., adjacent vertebral osteomyelitis and diskitis--was studied in 80 adult patients. The infection was due to Mycobacterium tuberculosis in 31 cases (39%) and to pyogenic bacteria in 49 cases (61%). The latter pathogens included gram-negative bacilli in 16 cases (20%), Staphylococcus species in 15 (19%), Streptococcus species in 9 (11%), and Corynebacterium species in 1 (1%); the pathogens in the 8 remaining cases (10%) were not identified. Of the patients with tuberculous spondylodiskitis, 55% came from countries where tuberculosis is endemic (P < .001). Cases due to staphylococci and those due to M. tuberculosis were associated with a high frequency of previous active infection with those respective organisms at any site (47% and 42%, respectively; P < .001) and with a high rate of neurological complications (33% and 32%, respectively; P < .001). Nine patients with pyogenic spondylodiskitis (18%) but only one patient with tuberculous spondylodiskitis (3%) had diabetes mellitus (P < .05). Blood cultures were positive in 23 (56%) of the 41 cases of pyogenic spondylodiskitis due to an identified bacterium. Discovertebral needle biopsy contributed to the bacteriologic diagnosis in 29 (74%) of 39 cases.

Adult↗