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Biomedical subjects

Dominique Batisse

Publications and source records attributed to Dominique Batisse.

8 recordsLinked to original sources

Alteration of cytochrome oxidase subunit I labeling is associated with severe mitochondriopathy in NRTI-related hepatotoxicity in HIV patients.

Liver mitochondrial toxicity induced by nucleoside reverse transcriptase inhibitors (NRTI) in human immunodeficiency virus (HIV) patients has been associated with a wide range of liver involvement ranging from low-grade hepatotoxicity, asymptomatic lactacidemia to severe liver insufficiency, with massive steatosis and life-threatening lactic acidosis. Considerable efforts have been made in the last few years to establish clinical guidelines to avoid life-threatening NRTI-associated lactic acidosis. However, the important issue of low-grade NRTI-associated hepatotoxicity still needs to be unravelled since its natural history is largely unknown. We have recently reported a series of 13 monoinfected HIV patients with low-grade NRTI-associated toxicity. Our results outlined the heterogeneity of NRTI-induced hepatotoxicity and raised the question of its diagnosis. The present study evaluates the expression of cytochrome oxidase (COX) subunits I and IV, encoded by mitochondrial and nuclear DNA, respectively, in NRTI hepatotoxicity. The aim of our study was to compare the detection rate of mitochondrial abnormalities of immunohistochemistry for COX subunit I with electron microscopy. COX subunit I and IV labeling was performed together with light microscopy and ultrastructural analysis in a series of 55 liver biopsies from HIV monoinfected and HIV-hepatitis C virus coinfected patients. Clinical data were also recorded. Our major findings were: (i) decreased COX subunit I labeling is associated with severe ultrastructural mitochondrial alterations and may represent overt NRTI-induced mitochondrial cytopathy; (ii) mild ultrastructural damage associated with normal COX subunit I labeling is of unknown clinical significance. The results of the study suggest that COX subunit I labeling may be a valuable tool for the diagnosis of mitochondrial liver disease in HIV patients.

Adult↗

Sexually transmitted acute infection with a clustered genotype 4 hepatitis C virus in HIV-1-infected men and inefficacy of early antiviral therapy.

BACKGROUND: Recent studies have suggested an increased risk of acute hepatitis C (HCV) infection in homosexual HIV-infected men and that early treatment with standard or pegylated interferon-alfa, alone or associated with ribavirin, significantly reduces the risk of chronic evolution in HIV-infected patients. METHODS: A retrospective analysis of 12 HIV-infected patients who were consecutively diagnosed as developing acute HCV infection, defined by both seroconversion of anti-HCV antibodies and detection of serum HCV RNA in those with previous negative results. Ten of these patients received early antiviral treatment with standard or pegylated interferon-alfa, alone or associated with ribavirin. RESULTS: The only risk factor in these patients was unprotected sexual intercourse with men. Acute HCV infection was asymptomatic in 10 patients, and the HCV genotype was 4d in 10 patients. The 10 genotype 4d viruses formed a monophylogenetic group and clustered separately from other local sequences of HCV genotype 4d, suggesting a common source of infection. None of the 10 patients who were treated early with antiviral therapy had a sustained virological response, as defined by undetectable HCV RNA 6 months after therapy. CONCLUSIONS: There is a risk of sexual transmission of HCV in HIV-infected men who have sex with men; the cluster of HCV genotype 4d suggested a common source of infection and a failure in prevention counselling. Early treatment with standard interferon-alfa failed to prevent chronic evolution of HCV infection in this particular group of HIV-infected patients who had acquired this peculiar cluster of genotype 4 strains.

Acute Disease↗

Capacitance imaging of the skin surface.

BACKGROUND/AIMS: A new device allowing recording capacitance images of the skin surface was recently presented. Parameters, extracted from the gray-level histogram of the images, are tested for a new approach of skin surface hydration measurement in comparison with the classical capacitance method. Illustration of the interest of having both images and parameters for studying the homogeneity and the level of skin surface hydration are presented. METHODS: Software for selecting a region of interest from an image and measuring the parameters derived from its gray-level histogram was used to characterize skin hydration. RESULTS: There is a very close correlation between a Corneometer and the parameters extracted from the SkinChip measurements. The importance of having capacitance images of skin is demonstrated in case of non-homogeneity of the skin hydration, either because of photoaging or following an inflammation process. CONCLUSION: Capacitance imaging is a necessary tool for both completely describing and quantifying skin surface hydration.

Dermatitis↗

[Mitochondrial hepatic toxicity associated with antiretroviral treatment].

Highly active antiretroviral therapy (HAART) has become the gold standard treatment of HIV/AIDS infection. NRTI-related mitochondrial toxicity has been recognized as a serious adverse effect of HAART. The mechanisms underlying NRTI-induced mitochondriopathy involve the inhibition of the human DNA polymerase gamma mtDNA mutations and oxidative stress. The clinical spectrum of NRTI-related toxicity ranges from a subclinical disease e.g. mild hepatic abnormalities, to a rare life-threatening condition with lactic acidosis and hepatic insufficiency. In the latter, liver histology shows massive steatosis. Ultrastructural assessment of mitochondrial abnormalities may be of help to address the NRTI toxicity in poorly symptomatic patients. Efforts have been recently made to assess the clinical relevance of non-invasive tests including the evaluation of mtDNA or mitochondrial functions in peripheral blood mononuclear cells for the diagnosis of NRTI-associated toxicity.

Acquired Immunodeficiency Syndrome↗

Sustained exacerbation of cryoglobulinaemia-related vasculitis following treatment of hepatitis C with peginterferon alfa.

Peginterferon is now the gold standard of therapy in patients with chronic hepatitis C virus infection. Extrahepatic manifestations of HCV are usually treated with interferon alfa. Here we report on a patient with HCV-related cirrhosis and cryoglobulinaemia who presented with an acute and long-lasting exacerbation of vasculitis during treatment with peginterferon. To our knowledge this is the first report of an acute exacerbation of cryoglobulinaemia-related vasculitis involving skin, peripheral nerve and kidney in a patient treated with peginterferon for HCV-related cirrhosis. The long half-life of peginterferon might explain the long-lasting symptoms of vasculitis. Clinicians should be aware of possible sustained flare of cryoglobulinaemia-associated vasculitis in patients receiving peginterferon.

Adult↗

Toxic effects of nucleoside reverse transcriptase inhibitors on the liver. Value of electron microscopy analysis for the diagnosis of mitochondrial cytopathy.

Nucleoside reverse transcriptase inhibitors (NRTIs) induce mitochondrial toxic effects resulting in multiple organ disorders. Liver involvement has been associated mainly with severe lactic acidosis and massive steatosis. However, patients with HIV infection who are receiving antiretroviral treatment frequently have mildly abnormal liver test results that, to date, have not been linked unambiguously to the toxic effects of NRTIs. Thirteen patients with HIV infection treated with NRTI-based regimens had low-grade abnormal liver test results associated with digestive and nonspecific general symptoms. Histologic examination of liver samples showed diffuse steatosis in only 6 cases and mild steatosis in the remaining cases, associated with megamitochondria, mild lobular inflammation and necrosis, Mallory bodies, and perisinusoidal fibrosis. In all cases, ultrastructural study disclosed mitochondrial abnormalities. Our work demonstrates that NRTI-induced toxic effects in the liver may occur as indolent nonspecific disease with variable histologic features and emphasizes the diagnostic value of electron microscopy, particularly when diffuse steatosis is absent.

Adult↗

Influence of age on the wrinkling capacities of skin.

BACKGROUND: Comparisons of clinical assessment with measurement of physical parameters are rare. OBJECTIVE: To standardize the horizontal wrinkling of the skin in order to define a reference chart of the different wrinkling grades and to propose an interpretation of the clinical pattern in terms of skin layers thickness and mechanical parameters. METHODS: A device allowing reproducible wrinkling of the skin was made. The skin folds created in this way were clinically assessed on women of different ages. Measurements of the mechanical properties of the skin were carried out by using a Torquemeter. Skin layers' thicknesses were measured by using in vivo Confocal Microscopy (CM) and Ultrasound Imaging (B mode). RESULTS: Skin wrinkling grades increase versus age. Skin elasticity, extensibility and echogenicity decrease also versus age and the wrinkling grade. Wrinkling appears to be related to skin rigidification (for both stratum corneum and dermis) coupled to a certain weakening of the upper dermis (loss of echogenicity). CONCLUSION: This study points out the key role of the age-related alterations of the upper dermis in skin wrinkling capacities.

Adult↗

A computational skin model: fold and wrinkle formation.

This paper presents a computational model for studying the mechanical properties of skin with aging. In particular, attention is given to the folding capacity of skin, which may be manifested as wrinkles. The simulation provides visual results demonstrating the form and density of folds under the various conditions. This can help in the consideration of proper measures for a cosmetic product for the skin.

Aging↗