Search PubMed⌕ Search

Biomedical subjects

P Leclercq

Publications and source records attributed to P Leclercq.

At least 19 recordsLinked to original sources

The mitochondrial consequences of uncoupling intact cells depend on the nature of the exogenous substrate.

In isolated mitochondria the consequences of oxidative phosphorylation uncoupling are well defined, whereas in intact cells various effects have been described. Uncoupling liver cells with 2,4-dinitrophenol (DNP) in the presence of dihydroxyacetone (DHA) and ethanol results in a marked decrease in mitochondrial transmembrane electrical potential (DeltaPsi), ATP/ADP ratios and gluconeogenesis (as an ATP-utilizing process), whereas the increased oxidation rate is limited and transient. Conversely, when DHA is associated with octanoate or proline, DNP addition results in a very large and sustained increase in oxidation rate, whereas the decreases in DeltaPsi, ATP/ADP ratios and gluconeogenesis are significantly less when compared with DHA and ethanol. Hence significant energy wastage (high oxidation rate) by uncoupling is achieved only with substrates that are directly oxidized in the mitochondrial matrix. Conversely in the presence of substrates that are first oxidized in the cytosol, uncoupling results in a profound decrease in mitochondrial DeltaPsi and ATP synthesis, whereas energy wastage is very limited.

Adenosine Diphosphate↗

Change in transaminases in hepatitis C virus- and HIV-coinfected patients after highly active antiretroviral therapy: differences between complete and partial virologic responders?

Patients with HIV and hepatitis C virus (HCV) coinfection have more severe hepatitis-related disease than do patients with HCV infection alone. Highly active antiretroviral therapy (HAART) with protease inhibitor appears to restore pathogen-specific immune responses, especially in patients with persistent undetectable HIV viral load. To evaluate the potent impact of immune restoration induced by HAART on the course of HCV-related disease, HCV viremia and levels of transaminases were compared between two groups of patients: 10 HIV/HCV-coinfected patients with persistently undetectable HIV viremia (group A) and 12 HIV/HCV-coinfected patients with persistent detectable HIV viremia. No difference was detected in HCV viral load in either group. An increase in transaminases was found only in patients with persistent undetectable HIV viral load, which was correlated with the increase in CD8+ T cells. This may suggest that the restoration of CD8+ T cell cytotoxicity could lead to an enhancement of hepatitis C-related disease in HCV/HIV-coinfected patients receiving HAART.

Adult↗

[Experience with an "isolation unit" for patients infected with multi-resistant bacteria. Retrospective study of 49 patients].

OBJECTIVES: Perform a retrospective analysis of care in a hospital "isolation unit" for patients infected with multirestant bacteria (MRB), i.e. meticillin-resistant staphylococcus aureus (SAMR), broad spectrum beta-lactamase secreting enterobacteria. (BLSE). PATIENTS AND METHODS: Forty-nine patients infected with MRB were cared for in our hospital isolation unit between January 1, 1996 and January 1, 1997. Each patient was in a separate room equipped with a sink and soap distributor, single-use towels, and individual material for patient care (stethoscope, mobile equipment, writing material, etc.). The personnel were given special training in the prevention of nosocomial infections. At admission, and in all patients, bacteriological samples to search for SAMR were acquired from nasal discharge, urine, perineal swabs, wounds and bed sores. Wound, urine and fecal samples were also taken to search for BLSE. Search for other sites of infection depended on the clinical situation. The management protocol in the isolation unit included: isolation, daily antiseptic baths, topical application of antibiotics or antiseptics on all bacteriologically proven sites of SAMR infection, selective decontamination of the digestive tract for patients with BLSE positive stools. Systemic antibiotics were given case by case. RESULTS: Mean duration of stay in the isolation unit was 17 days for SAMR infections and 14 days for BLSE infections. Mean delay to sterilization of the infected sites varied depending on the localization: 2.3 days for blood and 19.4 days for stools. Seven patients died. After leaving the isolation unit, the bacteriological course was followed in 23 patients: there were 7 cases of recurrence at least one site within a mean delay of 34.5 days. CONCLUSION: Use of isolation units provides an interesting solution for health care centers to control spread of multiresistant bacteria. Considering the endemic state of multiresistant bacteria infections in French hospitals, each health care unit should have correctly equipped facilities for isolating infected patients.

Drug Resistance, Microbial↗

Association between primary cytomegalovirus infection and severe hemolytic anemia in an immunocompetent adult.

Hemolysis is a rare complication of cytomegalovirus infection in the immunocompetent adult, and the mechanisms responsible for it remain obscure. Guidelines for treatment have yet to be established, and the effectiveness of antiviral therapy has not been proven. In this report, an unusual case of primary cytomegalovirus infection manifested by severe hemolysis in an immunocompetent adult is presented. Treatment with ganciclovir (5 mg/kg b.i.d.) for 10 days and prednisolone (2 mg/kg/day) for more than 3 months suggests that both virological and immunological mechanisms are probably responsible for the hemolysis.

Adult↗

Human herpesvirus 8 and Epstein Barr-virus in a cutaneous B-cell lymphoma and a malignant cell line established from the blood of an AIDS patient.

Human Herpesvirus 8 (HHV-8) has been consistently associated with Primary Effusion Lymphoma (PEL or body-cavity-based lymphoma) but not with other lymphomas. This paper reports on an AIDS patient without obvious malignant effusion in body cavities but with a cutaneous lymphoma where HHV-8 and Epstein-Barr virus (EBV) were detected by PCR and electron microscopy. Both viruses were also detected in all the cells of a malignant cell line (BBG1) established from the patient's peripheral blood mononuclear cells. As in PEL and PEL-derived cell lines, both the tumor and the lines lacked B-antigen expression in immunological studies but were of the same B origin as shown by clonal immunoglobulin gene rearrangements. In contrast to other co-infected cell lines, BBG1 and subclones spontaneously expressed the HHV-8 lytic antigens p40, p27, p60 and the EBV transforming latent antigen EBNA2. These data suggest that the clinical and biological features of HHV-8-and EBV-associated lymphomas could be wider than has been described to date in PEL particularly with the in vivo presence of circulating malignant dually-infected cells engaged in a spontaneous HHV-8 lytic infection.

Acquired Immunodeficiency Syndrome↗

[Effects of double and triple antiretroviral agents on the HCV viral load in patients coinfected with HIV and HCV].

HIV infection accelerates natural course of HCV infection, but impact of antiretroviral treatment on HCV infection is not well known. The aim of this study is to compare the change of HCV viral load in patients on combination of 2 nucleoside analogues and in patients on combination of 2 nucleoside analogues and protease inhibitor. HCV and HIV viral load, lymphocyte CD4 counts, alanine aminotransferase (ALT) and aspartate amino transferase (AST) were measured before and 3 months after starting treatment in 2 groups: Group 1 (n = 15) treated with 2 nucleoside analogues and Group 2 (n = 15) treated with 2 nucleoside analogues and a protease inhibitor. Results show a significant increase in lymphocyte and a significant decrease in HIV viral load in the both group but no significant change in HCV viral load and in ALT and AST. In conclusion efficiency of anti-HIV therapy (combination of 2 nucleoside analogues with or without a protease inhibitor) doesn't seem to have any impact on the course of HCV viremia in HIV-coinfected patients.

AIDS-Related Opportunistic Infections↗

Inhibition of glycerol metabolism in hepatocytes isolated from endotoxic rats.

Sepsis or endotoxaemia inhibits gluconeogenesis from various substrates, the main effect being related to a change in the phosphoenolpyruvate carboxykinase transcription rate. In addition, sepsis has been reported to affect the oxidative phosphorylation pathway. We have studied glycerol metabolism in hepatocytes isolated from rats fasted and injected 16 h previously with lipopolysaccharide from Escherichia coli. Endotoxin inhibited glycerol metabolism and led to a very large accumulation of glycerol 3-phosphate; the cytosolic reducing state was increased. Furthermore glycerol kinase activity was increased by 33% (P<<0.01). The respiratory rate of intact cells was significantly decreased by sepsis, with glycerol or octanoate as exogenous substrates, whereas oxidative phosphorylation (ATP-to-O ratio or respirations in state 4, state 3 and the oligomycin-insensitive state as well as the uncoupled state) was unchanged in permeabilized hepatocytes. Hence the effect on energy metabolism seems to be present only in intact hepatocytes. An additional important feature was the observation of a significant increase in cellular volume in cells from endotoxic animals, which might account for the alterations induced by sepsis.

Adenine Nucleotides↗

Impact of protease inhibitors on AIDS-defining events and hospitalizations in 10 French AIDS reference centres. Fédération National des Centres de Lutte contre le SIDA.

OBJECTIVE: To assess the clinical and economic consequences of the use of protease inhibitors in the treatment of HIV infection. DESIGN: Multicentric, observational, retrospective cohort study. SETTING: Ten AIDS reference centres in France. PATIENTS: All patients followed in each centre from September 1995 through October 1996. MAIN OUTCOME MEASURES: AIDS-defining events, death, health-care resources use, administration of antiretroviral therapy. RESULTS: Data from 7749 patients in 10 centres showed a drop in hospitalization days by 35%, new AIDS cases by 35%, and deaths by 46%. In the same period, the proportion of patients receiving antiretrovirals rose from 36 to 53% including highly active antiretroviral therapy (HAART), which rose from 0.3 to 18%. Overall cost evaluation showed a slight increase of monthly treatment cost of US$ 12 per patient. Comparison of the three centres that used HAART earliest to the three centres that used it latest showed a clear benefit to early HAART with a drop in hospitalization days by 41%, new AIDS cases by 41% and deaths by 69%. The proportion of patients with HAART rose to 27% and monthly health-care cost decreased by US$ 248852 (i.e., by US$ 101 per patient per month). Late prescribing centres experienced a less marked effect with a drop in hospitalization days by 22%, new AIDS cases by 31%, and deaths by 32.5%. Proportion of patients with HAART rose to 12% and monthly health-care costs increased by US$ 113578 (i.e., by US$ 38 per patient per month). CONCLUSIONS: This study supports the extensive use of HAART in HIV-infected patients.

Acquired Immunodeficiency Syndrome↗

Diagnosis of 22 new cases of Bartonella endocarditis.

BACKGROUND: Bartonella species are emerging pathogens that are seldom reported as a cause of blood culture-negative endocarditis. OBJECTIVE: To report the occurrence of, risk factors for, and clinical features of Bartonella endocarditis and to evaluate the diagnostic tools available for this condition. DESIGN: Case series and comparison with past series. SETTING: Multicenter international study in Halifax, Nova Scotia, Canada; Lyon, France; and Marseille, France. PATIENTS: 22 patients from France, England, Canada, and South Africa were investigated for blood culture-negative endocarditis. MEASUREMENTS: Titer of antibodies to Bartonella species by microimmunofluorescence assay, blood or vegetation culture, and amplification of Bartonella DNA from valvular tissue by polymerase chain reaction. Cross-adsorption was done for patients with antibodies to Chlamydia species. RESULTS: 22 patients had definite endocarditis. Five were infected with B. quintana, 4 with B. henselae, and 13 with an undetermined Bartonella species. These cases were compared with the 11 previously reported cases. Of the patients with the newly reported cases, 19 had valvular surgery and 6 died. Nine were homeless, 11 were alcoholic, 4 owned cats, and 13 had preexisting valvular heart disease. Bartonella species caused 3% of the cases of endocarditis seen in the three study centers. The patients with these cases could have previously received a diagnosis of chlamydial endocarditis because of apparently high levels of cross-reacting antibodies to Chlamydia species. CONCLUSIONS: Bartonella species are an important cause of blood culture-negative endocarditis and can be identified by culture, serologic studies, or molecular biology techniques. Alcoholism and homelessness without previous valvular heart disease are risk factors for B. quintana infection but not for infection with other Bartonella species.

Adult↗

Sexually dimorphic expression of calcitonin gene-related peptide (CGRP) immunoreactivity by rat mediobasal hypothalamic neurons.

Although the hypothalamic arcuate nucleus is a sexually dimorphic region of the rat brain, there are no reports of sex differences in the number of neurons containing specific neuropeptides within this structure. As cells synthesizing calcitonin gene-related peptide (CGRP) have been shown to exhibit sex differences in other steroid-receptive regions of the rat brain, we examined whether the CGRP-immunoreactive cells located in the mediobasal hypothalamus may also be sexually dimorphic. Immunostaining of sections from male and female colchicine-treated rats revealed a small population of CGRP-immunoreactive cells distributed throughout the arcuate nucleus. Immunoreactive cells were also detected in the lateral hypothalamic perifornical region, dorsomedial, posterior periventricular and ventral tuberomammillary nuclei, and zona incerta. Cell count analysis revealed approximately twice as many CGRP-immunoreactive cell profiles in the rostral (P < 0.01), middle (P < 0.001), and caudal (P < 0.01) thirds of the arcuate nucleus of male rats compared with females. A significant sex difference in immunoreactive cell numbers (male > female) was also detected within the caudal dorsomedial nucleus (P < 0.05) but not in the posterior periventricular nucleus, perifornical region and zona incerta. Although fibers immunoreactive for CGRP were identified in low density throughout the mediobasal hypothalamus, only female rats displayed prominent fiber staining in the periventricular region. Double-labelling immunofluorescence experiments revealed that the CGRP-immunoreactive cells within the zona incerta, but not the hypothalamus, were also immunoreactive for tyrosine hydroxylase; at least 60% of the A13 dopaminergic neurons co-express CGRP. These results provide evidence that sex differences exist in the number of specific neuropeptide-synthesizing cells within the hypothalamic arcuate nucleus and provide further examples of cell populations expressing CGRP immunoreactivity in a sexually dimorphic manner.

Animals↗