Biomedical subjects

Anne Garnier

Publications and source records attributed to Anne Garnier.

9 recordsLinked to original sources

PubMed2007

Evaluation of a combined screening programme for breast, cervical and colorectal cancers in France.

A combined breast, cervical and colorectal cancer screening programme was set up in 1990 in Isère, for women aged 50-69 years (target population 100,000) comprising an initial medical visit. The programme was evaluated in 1997. The evaluation covered uptake results, sensitivity, specificity, two opinion surveys among 1025 physicians and 400 women to measure the impact, and three surveys regarding radiologists', gastroenterologists' and pathologists' attitudes. Sensitivity and specificity rates were 74 and 87% for breast, 83 and 99% for cervical and 43 and 97% for colorectal screening. The number of cervical smears completed by women aged 60-69 years doubled with the programme. Acceptability of the faecal occult blood test was 88%. Eighty percent of physicians were in favour of the programme but 67% said that they often prescribed outside the programme. Overall, 71% of the interviewed women said they had had a breast screen, 69% a Pap smear and 53% a faecal occult blood test when only 25-35% of the target population was actually recorded in the programme. This programme increased the uptake of women not previously screened both within and outside the programme. It showed discrepancies between beliefs and practices of physicians. Protocol changes were implemented after this evaluation.

Aged↗

PubMed2006

Balloonborne lidar for cloud physics studies.

An innovative balloonborne microjoule lidar (MULID) has been developed within the framework of the HIBISCUS project to provide nighttime measurements of visible and subvisible cirrus and aerosols. MULID has been designed to be a low-cost and an ultralow consumption instrument, due to the remote possibilities of payload recovery and the necessity of a low-weight battery power supply. Ground tests have been performed at the Observatory of Haute Provence (France), and the first technical flight has been made from Trapani, Italy, on a stratospheric balloon; finally, the instrument has been scientifically deployed during the pre-HIBISCUS and HIBISCUS tropical campaigns in Bauru, Brazil, in February 2003 and February 2004, respectively. A description of the instrument is provided together with the results of the ground-based and flight tests as well as an overview and discussion of the first results.

Journal Article↗

PubMed2006

ACE inhibition prevents myocardial infarction-induced skeletal muscle mitochondrial dysfunction.

Heart failure is associated with alterations in cardiac and skeletal muscle energy metabolism resulting in a generalized myopathy. We investigated the molecular and cellular effects of angiotensin-converting enzyme inhibition (ACEi) on skeletal muscle metabolism in infarcted animals. Myocardial infarction (MI) was obtained by left descending coronary artery ligation. Sham, MI, and MI-treated rats (perindopril, 2 mg.kg(-1).day(-1) given 7 days after MI) were studied 1 and 4 mo after surgery. Oxygen consumption of white gastrocnemius (Gas) muscle was studied in saponin-permeabilized fibers, using the main substrates of mitochondrial respiration. mRNA expression of nuclear factors (PGC-1alpha, NRF-2alpha, and mtTFA), involved in the transcription of mitochondrial proteins, and of MCIP1, a marker of calcineurin activation, were also determined. Echocardiographic left ventricular fractional shortening was reduced in both MI and perindopril group after 1 and 4 mo, whereas systemic blood pressure was reduced by 16% only in the MI group after 4 mo. The capacity of Gas to oxidize glutamate-malate, glycerol-triphosphate, or pyruvate (-30%, P < 0.01; -32%, P < 0.05; -33%, P < 0.01, respectively), was greatly decreased. Furthermore, PGC-1alpha (-54%), NRF-2alpha (-45%), and MCIP1 (-84%) gene expression were significantly downregulated. ACEi improved survival, left ventricular function, and blood pressure. Perindopril protected also totally the Gas mitochondrial function and preserved the mRNAs concentration of the mitochondrial transcriptional factors. Moreover, PGC-1alpha correlated with Gas oxidative capacity (r = 0.48), mitochondrial cytochrome-c oxidase (r = 0.65), citrate synthase (r = 0.45) activities, and MCIP1 expression (r = 0.44). Thus ACEi totally prevented MI-induced alterations of skeletal muscle mitochondrial function and protein expression, halting the development of this metabolic myopathy.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2005

cAMP-binding protein Epac induces cardiomyocyte hypertrophy.

cAMP is one of the most important second messenger in the heart. The discovery of Epac as a guanine exchange factor (GEF), which is directly activated by cAMP, raises the question of the role of this protein in cardiac cells. Here we show that Epac activation leads to morphological changes and induces expression of cardiac hypertrophic markers. This process is associated with a Ca2+-dependent activation of the small GTPase, Rac. In addition, we found that Epac activates a prohypertrophic signaling pathway, which involves the Ca2+ sensitive phosphatase, calcineurin, and its primary downstream effector, NFAT. Rac is involved in Epac-induced NFAT dependent cardiomyocyte hypertrophy. Blockade of either calcineurin or Rac activity blunts the hypertrophic response elicited by Epac indicating these signaling molecules coordinately regulate cardiac gene expression and cellular growth. Our results thus open new insights into the signaling pathways by which cAMP may mediate its biological effects and identify Epac as a new positive regulator of cardiac growth.

Active Transport, Cell Nucleus↗

PubMed2005

Coordinated changes in mitochondrial function and biogenesis in healthy and diseased human skeletal muscle.

We examined the transcriptional signaling cascade involved in the changes of mitochondrial biogenesis and mitochondrial function of skeletal muscle and of the exercise capacity of humans in response to long-term physical activity and chronic heart failure (CHF). Biopsy samples of vastus lateralis muscle were obtained from 18 healthy subjects with different fitness levels (assessed by maximal oxygen uptake, VO2 peak). We compared 9 sedentary subjects with 10 CHF patients undergoing transplantation. Muscle oxidative capacity was measured in permeabilized fibers (Vmax). Transcript levels of target genes were quantified by RT-PCR. In healthy subjects, VO2 peak was linearly related to Vmax (P<0.01) and to the gene expression of mitochondrial proteins and of the coactivator PGC-1alpha and its downstream transcription factors. A coordinate increase in PGC-1alpha and mRNA levels of proteins involved in degradation, fusion, and fission of mitochondria was observed associated with calcineurin activation. Despite decreased VO2 peak, in CHF patients skeletal muscles showed preserved Vmax in accordance with preserved markers and transcription factors of mitochondrial biogenesis and dynamics, with no calcineurin activation. The results provide strong support for a central role for PGC-1alpha and calcineurin activation in mitochondrial biogenesis in healthy and diseased human skeletal muscles.

Biopsy↗

PubMed2004

Cardiac specific increase in aldosterone production induces coronary dysfunction in aldosterone synthase-transgenic mice.

BACKGROUND: Elevated circulating aldosterone level is associated with impaired cardiovascular function. Although the mechanisms are not fully understood, aldosterone antagonists decrease total and cardiovascular mortality in heart failure and myocardial infarction. Aldosterone induces cardiac fibrosis in experimental models, and it is synthesized locally in rat heart. These observations suggest pathological effects of aldosterone in heart that remain unclear. METHODS AND RESULTS: Transgenic mice (TG) that overexpress the terminal enzyme of aldosterone biosynthesis, aldosterone synthase (AS), in heart have been raised by gene targeting with the alpha-myosin heavy chain promoter. AS mRNA increased 100-fold and aldosterone concentration 1.7-fold in hearts of male TG mice relative to wild-type. No structural or myocardial alterations were evidenced, because ventricle/body weight, AT1 and AT2 receptor binding, and collagen content were unchanged in TG. No alteration in cardiac function was evidenced by echocardiography, isolated perfused heart, or whole-cell patch clamp experiments. In contrast, coronary function was impaired, because basal coronary flow was decreased in isolated perfused heart (-55% of baseline values), and vasodilatation to acetylcholine, bradykinin, and sodium nitroprusside was decreased by 75%, 60%, and 75%, respectively, in TG mice compared with wild-type, showing that the defect was not related to NO production. CONCLUSIONS: Increased cardiac aldosterone production in male mice induces a major coronary endothelium-independent dysfunction with no detectable alterations in cardiac structure and function. However, coronary dysfunction may be harmful for coronary adaptation to increased flow demand.

Acetylcholine↗

PubMed2004

Wind-velocity lidar measurements by use of a Mach-Zehnder interferometer, comparison with a Fabry-Perot interferometer.

We present the first wind-velocity profiles obtained with a direct-detection Doppler lidar that uses a Mach-Zehnder interferometer (MZI) as spectral discriminator. The measurements were performed in the lower stratosphere, between 10 and 40 km in altitude, at the Observatoire de Haute Provence (OHP), France, during nighttime. They are in excellent agreement with those obtained simultaneously and independently with the already validated double Fabry-Perot interferometer (FPI) of the OHP Doppler lidar (mean difference lower than the combined standard deviation). A statistical analysis shows that the random error obtained with this experimental MZI is 1.94 times the Cramer-Rao lower bound and is approximately half of that given by the FPI (both operating in photometric mode). Nevertheless, the present MZI measurements are sensitive to the presence of atmospheric particles and need an additional correction, whereas the OHP FPI is designed to be insensitive to particulate scattering.

Journal Article↗

PubMed2003

Energy metabolism in heart failure.

Heart failure (HF) is a syndrome resulting from the inability of the cardiac pump to meet the energy requirements of the body. Despite intensive work, the pathogenesis of the cardiac intracellular abnormalities that result from HF remains incompletely understood. Factors that lead to abnormal contraction and relaxation in the failing heart include metabolic pathway abnormalities that result in decreased energy production, energy transfer and energy utilization. Heart failure also affects the periphery. Patients suffering from heart failure always complain of early muscular fatigue and exercise intolerance. This is linked in part to intrinsic alterations of skeletal muscle, among which decreases in the mitochondrial ATP production and in the transfer of energy through the phosphotransfer kinases play an important role. Alterations in energy metabolism that affect both cardiac and skeletal muscles argue for a generalized metabolic myopathy in heart failure. Recent evidence shows that decreased expression of mitochondrial transcription factors and mitochondrial proteins are involved in mechanisms causing the energy starvation in heart failure. This review will focus on energy metabolism alterations in long-term chronic heart failure with only a few references to compensated hypertrophy when necessary. It will briefly describe the energy metabolism of normal heart and skeletal muscles and their alterations in chronic heart failure. It is beyond the scope of this review to address the metabolic switches occurring in compensated hypertrophy; readers could refer to well-documented reviews on this subject.

Animals↗

PubMed2002

[Yield of colonoscopy by indication and consequences for colorectal polyp and cancer screening: a prospective survey in Isère, France].

AIM: The aim of this study was to determine yields of colonoscopy by indication, especially after a positive Hemoccult test, in the Isère area in southeastern France where a mass screening campaign for colorectal cancer using the Hemoccult test was conducted in women aged 50 to 69 years. METHOD: This prospective survey was conducted with the participation of all gastroenterologists in the Isère department. Information about indications of all colonoscopies performed and their results were collected. RESULTS: The study involved 1,779 colonoscopies performed for: digestive symptoms (40%), surveillance of colon disease (22%), hematochezia (18%), a family history of colon cancer (10%), anemia, poor general condition or metastasis (4%), and a positive test for blood in the stool (3%). The presence of a pathological colonic condition was significantly related to age (11% of cancers or large polyps after 50 years compared to 3% before), sex (10% of the women with lesions and 15% of the men) and the reason for prescription: after the age 50 a cancer or a large polyp was found in 27% of the cases if the colonoscopy was performed for anemia, metastasis or poor general condition, 21% for hematochezia, 20% for a positive test, 8% for digestive symptoms, and 2% because of a family history. CONCLUSION: Positive Hemoccult tests represent only a small part of the indications for colonoscopies performed in the Isère department. However, the screening program should be extended to develop its use given its yield which is equivalent to that of hematochezia and much higher than that of digestive symptoms or family history.

Adult↗