Françoise Roudot‐Thoraval

Assistance Publique – Hôpitaux de Paris

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Daniel Dhumeaux

Université Paris-Est Créteil

Jean‐Michel Pawlotsky

Université Paris-Est Créteil

Christophe Hézode

Gilead Sciences (United States)

Ariane Mallat

Hôpitaux Universitaires Henri-Mondor

Dominique Roulot

Assistance Publique – Hôpitaux de Paris

Richard Layese

Assistance Publique – Hôpitaux de Paris

Pierre Nahon

Université Paris Cité

Stanislas Pol

Institut Cochin

Patrick Marcellin

Hôpital Beaujon

Philippe Mathurin

Hôpital Claude Huriez

Cooperative Institutions

Inserm

869

Assistance Publique – Hôpitaux de Paris

764

Université Paris Cité

481

Université Paris-Est Créteil

394

Sorbonne Université

327

Hôpitaux Universitaires Henri-Mondor

314

Centre Hospitalier Universitaire Henri-Mondor

291

Centre National de la Recherche Scientifique

188

Institut Mondor de Recherche Biomédicale

181

Sorbonne Paris Cité

146

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Bloodstream Infection in Adults With Sickle Cell Disease

Medicine (2006)

Virginie Zarrouk Anoosha Habibi Jean‐Ralph Zahar Françoise Roudot‐Thoraval Dora Bachir

Although well documented in children with sickle cell disease (SCD), the incidence, cause, and outcome of bloodstream infection (BSI) are poorly defined in adults with SCD. Through a 5-year retrospective analysis of a cohort of 900 patients followed at our institution, we identified 56 episodes of BSI in 47 patients. The incidence rate of BSI was 1.2 episodes per 100 patient-years. As compared to the patients followed in the cohort, those with BSI were more likely to be younger (p = 0.001), to have Hb-S disease (p = 0.008), severe disease (p = 0.001), or additional immunosuppression (p = 0.05). BSI was hospital-acquired in 46% of cases and mainly associated with venous catheters (41%) and Staphylococcus aureus (34%). Pneumococci were rarely identified (10.7%). Despite an adequate duration of antibiotic therapy, the course of BSI was marked by a high frequency of associated bone-joint infection. Bone-joint infection was noted in 18 patients (32% of episodes) and occurred either during the initial BSI episode (13 patients) or 1-6 months after BSI resolution (5 patients). Factors associated with the occurrence of bone-joint infection were previous osteonecrosis (relative risk, 2.5; 95% confidence interval, 1.2-5.3) and S. aureus infection (relative risk, 3.8; 95% confidence interval, 1.8-8.4). In conclusion, BSI is a rare event in adults with SCD compared to children. It mainly occurs in those with a severe underlying disease and a venous catheter. These patients have a high risk of associated bone-joint infection and therefore must be closely monitored. Abbreviations: BSI = bloodstream infection, SCD = sickle cell disease, VOC = vaso-occlusive crisis.

10.1097/01.md.0000197023.46846.1c

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Citations (41)

β₂-Adrenergic Signaling in Human Heart: Shift from the Cyclic AMP to the Arachidonic Acid Pathway

Molecular Pharmacology (2003)

Catherine Pavoine Niloufar Behforouz Chantal Gauthier Sabine Le Gouvello Françoise Roudot‐Thoraval

We have recently established that enhancement of intracellular calcium cycling and contraction in response to β₂-adrenergic receptor (β₂-AR) stimulation exclusively relies on the activation of the cytosolic phospholipase A₂ (cPLA₂) and arachidonic acid production, via a pertussis toxin-sensitive G protein (possibly Gi), in embryonic chick cardiomyocytes. We aimed to investigate the relevance of the β₂-AR/Gi/cPLA₂ pathway in the human myocardium. In left ventricular biopsies obtained from explanted hearts, β₂-AR stimulation exerted either an inhibition of cPLA₂ that was insensitive to pertussis toxin (PTX) treatment, or an activation of cPLA₂, sensitive to PTX treatment. In right atrial appendages from patients who were undergoing open heart surgery, we demonstrated that β₂-AR-induced activation of cPLA₂ was favored in situations of altered β₁-AR and/or β₂-AR/adenylyl cyclase (AC) stimulations. Alterations were characterized by an increase in EC₅₀value of norepinephrine and a decrease in the maximal AC activation in response to zinterol, respectively. Quantitative reverse transcription-polymerase chain reaction analyses highlighted a positive correlation between the expression of AC5 and AC6 mRNAs in human cardiac atria, which suggested that functional alterations in AC responses were unlikely to be related to changes in the AC5/AC6 mRNA ratio. In addition, the shift from the cyclic AMP to the arachidonic acid pathway was not supported at the transcriptional level by opposite regulation of AC and cPLA₂mRNAs expression. This study gives the first evidence of the recruitment of cPLA₂by β₂-ARs in the human heart and suggests that the Gi/cPLA₂pathway could substitute for a deficient Gs/AC pathway in mediating β₂-AR responses.

10.1124/mol.64.5.1117

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Citations (30)

In Vivo Comparative Study of Two Lactobionate Based Solutions for Prolonged Heart Preservation

The International Journal of Artificial Organs (1995)

Christophe Baufreton C. Charloux Paul‐Alain Jaffrès M. Paul Françoise Roudot‐Thoraval

The duration of safe heart preservation must be improved. Using a heterotopic heart transplantation model, we compared in vivo the recovery of rabbits hearts preserved with a K + Lactobionate based fluid (UW: University of Wisconsin solution) or with a Na + Lactobionate based fluid. In the “preservation” group, hearts were cold stored (4°C) for 6 hours with UW (n=9) or Na + Lactobionate solution (n=9). In the “transplantation” group, cold storage was followed by 3 hours of reperfusion (UW: n=8, Na + Lactobionate solution: n=7). Functional recovery, adenine nucleotide pool, circulating blood cardiac enzymes, circulating blood and tissue malondialdehyde (MDA) were measured. Left ventricular enddiastolic and developed pressures at different preload levels were better after preservation with UW than with Na+Lactobionate solution (p<0.05). Also with UW, adenosine diphosphate and total adenine nucleotide content were significantly higher than with Na + Lactobionate solution (p<0.05) whereas adenosine triphosphate, monophosphate and energy charges were similar. Cardiac enzymes and tissue MDA were similar with UW and Na + Lactobionate solution. In circulating blood, MDA was not detected. These results enhance the superiority of UW solution over a Na + Lactobionate based solution for long term heart preservation.

Viaspan

Adenine nucleotide

Preload

Adenosine triphosphate

10.1177/039139889501800505

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Citations (2)

Epidemiological factors affecting the severity of hepatitis C virus-related liver disease: A French survey of 6,664 patients

Hepatology (1997)

Françoise Roudot‐Thoraval Anne Bastie Jean‐Michel Pawlotsky Daniel Dhumeaux

Cirrhosis is a frequent and severe event in the course of chronic hepatitis C, but it is unclear why some patients develop cirrhosis after a given period whereas others do not. We studied a large cohort of patients with chronic hepatitis C to determine the role of the route of transmission of hepatitis C virus (HCV) in the onset of cirrhosis. Six thousand six hundred sixty-four patients were enrolled in a nationwide survey of chronic hepatitis C in France. We first randomly defined a representative sample of 30 hospitals with medical units managing patients with HCV infection. All patients with chronic hepatitis C were enrolled if hepatitis C was diagnosed or treated in these units in 1991, 1992, or 1993. A questionnaire was filled in from the patients' charts and covered demographic data, risk factors for HCV infection, clinical and histological data, hepatitis B virus (HBV) and human immunodeficiency virus status, and alcohol intake. Descriptive statistics were prepared, and factors potentially related to the onset of cirrhosis were identified by means of univariate analysis followed by stepwise logistic regression analysis. Among the patients enrolled, 21.4% had biopsy-proven cirrhosis. Prevalence of cirrhosis markedly varied according to the route of transmission of HCV. It was significantly more frequent in blood recipients (23.4%) than in drug users (7.0%). Although the occurrence of cirrhosis was dependent on disease duration, it remained more frequent in blood recipients than in drug users for a given duration. Apart from the route of transmission, excessive alcohol intake was also associated with a higher risk of cirrhosis (34.9% vs. 18.2%; P < .001), and so was HBV infection (24.6% vs. 21.1%; P < .05). These factors acted independently of the route of transmission. Hepatocellular carcinoma was observed in 3.6% of all patients and in 17.8% of cirrhotic patients, and its occurrence was strongly and mainly related to the presence of cirrhosis. In conclusion, cirrhosis occurred in about 20% of the HCV-infected patients in this study and was more frequent in blood recipients than in drug users, independently of disease duration. Expected changes in the epidemiology of HCV infection might modify the risk of developing cirrhosis and, thereafter, cancer.

Hepatitis C

Liver disease

Hepatitis B

Chronic liver disease

Univariate analysis

10.1002/hep.510260233

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Citations (305)

[Prevalence of HBs antigen carriers and markers of B virus replication in a population of pregnant women, in France].

PubMed (1989)

Françoise Roudot‐Thoraval F Kouadja V Wirquin Valérie Thiers P Avons

HBeAg

Carriage

Source

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Citations (10)

Identification of MEFV-Independent Modifying Genetic Factors for Familial Mediterranean Fever

The American Journal of Human Genetics (2000)

Cécile Cazeneuve Hasmik Ajrapetyan Stéphanie Papin Françoise Roudot‐Thoraval David Geneviève

MEFV

AA amyloidosis

10.1016/s0002-9297(07)62944-9

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Citations (196)

[17] CANNABIS USE AS AN INDEPENDENT PREDICTOR OF SEVERE STEATOSIS DURING CHRONIC HEPATITIS C

Journal of Hepatology (2007)

C. Hézode Élie Serge Zafrani Françoise Roudot‐Thoraval Charlotte Costentin A. Hessami

Steatosis

Hepatitis C

10.1016/s0168-8278(07)61615-8

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Citations (0)

Hydroxychloroquine is a good second‐line treatment for adults with immune thrombocytopenia and positive antinuclear antibodies

American Journal of Hematology (2013)

Mehdi Khellaf Amélie Chabrol Matthieu Mahévas Françoise Roudot‐Thoraval Nicolas Limal

Treatment of patients with lupus‐associated thrombocytopenia (SLE‐ITP) is not standardized. We report data on efficacy and safety of hydroxychloroquine (HCQ) in this setting and in ITP patients with positive antinuclear antibodies (ANA) without definite SLE. Inclusion criteria were: definite diagnosis of ITP with a platelet count (PLT) <50 × 10 9 /L, ANA ≥ 1/160 on Hep2 cells with or without a definite diagnosis of SLE, and no sustained response to at least one previous treatment‐line and treatment with HCQ. Response criteria were Complete Response (CR) for PLT ≥ 100 × 10 9 /L and Response (R) for PLT ≥30 × 10 9 /L and at least twice the initial value. Forty patients (32 females) with a mean age of 35 ± 17 years and PLT at ITP diagnosis of 14 ± 13 × 10 9 /L were analyzed. Twelve (30%) patients had a SLE‐ITP, 28 patients had only positive ANA. All the patients failed to respond to oral prednisone with a median of two treatment‐lines (1–5) before HCQ which was initially given in combination with another ITP treatment in 36 patients. Overall response rate was 60% (24/40) including 18 lasting CR and six lasting R maintained with a median follow‐up of 64 months (6–146), in ¾ of cases with only HCQ and no concomitant ITP treatment. The response rate (CR+R) was higher in the SLE group vs ANA‐positive group (83% vs 50%, P < 0.05 ). No patient stopped HCQ because of a side‐effect. HCQ appears to be a safe and effective second line treatment for patients with SLE‐ITP or ITP and high titer of ANA. This trial was registered at www.clinicaltrials.gov as # NCT01549184. Am. J. Hematol. 89:194–198, 2014. © 2013 Wiley Periodicals, Inc.

Hydroxychloroquine

Concomitant

10.1002/ajh.23609

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Citations (51)

PIN151 PATIENTS TREATED FOR HEPATITIS C: AN OBSERVATIONAL STUDY WITH THE FRENCH ADMINISTRATIVE HEALTH CARE DATABASE (SNDS)

Value in Health (2019)

Simon van der Pol Ingrid Rodrı́guez F. Fouad Madleen Lemaître X. Ansolabehere

Hepatitis C

10.1016/j.jval.2019.09.1391

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Citations (1)

N -Acetylcysteine Treatment Normalizes Serum Tumor Necrosis Factor-α Level and Hinders the Progression of Cardiac Injury in Hypertensive Rats

Circulation (2004)

M. Bourraindeloup C. Adamy Gabriele Candiani Michel Cailleret M Bourin

Studies in isolated cardiomyocytes showed that replenishment in cellular glutathione, achieved with the glutathione precursor N-acetylcysteine (NAC), abrogated deleterious effects of tumor necrosis factor-alpha (TNF-alpha).We examined the ability of NAC to limit the progression of cardiac injury in the rat model of hypertension, induced by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) (50 mg/kg per day SC) and high-salt diet (HS) (8% NaCl). Four-week HS/L-NAME administration induced hypertension (193+/-8 versus 122+/-4 mm Hg for low-salt diet [LS] group) and left ventricular (LV) dysfunction, revealed by echocardiography and characterized by decreased LV shortening fraction (38+/-2% versus 49+/-4% for LS group; P<0.05) and decreased LV posterior wall thickening (49+/-3% versus 70+/-4% for LS group; P<0.05). LV dysfunction worsened further after 6-week HS/L-NAME administration. Importantly, increase in serum TNF-alpha level was strongly correlated with shortening fraction decrease and cardiac glutathione depletion. NAC (75 mg/d) was given as a therapeutic treatment in a subgroup of HS/L-NAME animals during weeks 5 and 6 of HS/L-NAME administration. NAC treatment, which replenished cardiac glutathione, had no effect on hypertension but reduced LV remodeling and dysfunction, normalized serum TNF-alpha level, and limited activation of matrix metalloproteinases -2 and -9 and collagen deposition in LV tissues.These findings suggest that glutathione status determines the adverse effects of TNF-alpha in cardiac failure and that TNF-alpha antagonism may be achieved by glutathione supplementation.

10.1161/01.cir.0000143630.14515.7c

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Citations (78)