Publications by authors named "François Blanc"

24 Publications

  • Page 1 of 1

PegIFNα/ribavirin/protease inhibitor combination in severe hepatitis C virus-associated mixed cryoglobulinemia vasculitis.

J Hepatol 2015 Jan 15;62(1):24-30. Epub 2014 Aug 15.

Department of Internal Medicine and Clinical Immunology, AP-HP, Hôpital Pitié-Salpétrière, DHU I2B, Immunopathology, Inflammation, Biotherapy, Paris, France; Université Pierre et Marie Curie, Paris VI, UMR CNRS 7211, INSERM U959, Hôpital Pitié-Salpétrière, Paris, France. Electronic address:

Background & Aims: The aim of this study was to analyse the safety and efficacy of the PegIFNα/ribavirin/protease inhibitor combination in severe and/or refractory hepatitis C virus (HCV)-mixed cryoglobulinemia (MC) vasculitis.

Methods: This prospective cohort study included 30 patients (median age 59 years [53-66] and 57% of women) with HCV-MC vasculitis. PegIFNα/ribavirin (for 48 weeks) was associated with telaprevir (375 mg three times daily, for 12 weeks, [n = 17]) or boceprevir (800 mg three times daily, for 44 weeks, (n = 13]).

Results: Twenty three patients (76.7%) were non-responders to previous antiviral therapy. At week 72, twenty patients (66.7%) were complete clinical and sustained virological responders. The cryoglobulin level decreased from 0.45 to 0 g/L (p<0.0001) and the C4 level increased from 0.09 to 0.14 g/L (p = 0.017). Complete clinical responders had a higher frequency of purpura (16/20 [80%] vs. 4/10 [40%], p = 0.045), and a trend towards lower frequency of neuropathy (9/20 (45%) vs. 8/10 [80%], p = 0.12) compared with partial responders. Serious adverse events occurred in 14 patients (46.6%) during the 72 weeks of follow-up. Twenty eight patients (93.3%) received erythropoietin, 14 (46.6%) had red blood cell transfusion and 2 (6.6%) received granulocyte stimulating agent. The baseline factors associated with serious adverse events included liver fibrosis (p = 0.045) and a low platelet count (p = 0.021).

Conclusions: The PegIFNα/ribavirin/protease inhibitor combination is highly effective in severe and/or refractory HCV-MC at the cost of frequent side effects. Baseline platelet count and liver fibrosis are useful in guiding treatment decisions.
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http://dx.doi.org/10.1016/j.jhep.2014.08.015DOI Listing
January 2015

Feasibility and Efficacy of an Addiction Treatment Program in Patients With Upper Aerodigestive Tract Cancer.

Subst Use Misuse 2014 Jan 6;49(1-2):103-109. Epub 2013 Aug 6.

e 5 Service ORL, Hôpital Gui de Chauliac , Montpellier, France.

Background: Continuing to smoke or to drink after the treatment of an upper aerodigestive tract (UADT) cancer is known to worsen the prognosis. We assessed the feasibility and efficacy of an addiction treatment program integrated into the cancer treatment.

Method: In four units devoted to UADT tumors, we proposed an addiction treatment to all patients still drinking or smoking at the end of the cancer treatment; the abstinence rate was assessed 6 and 12 months later.

Results: One hundred and sixteen patients were included. Among the 73 patients still drinking and/or smoking at the end of the cancer treatment, 46.6% accepted an addiction treatment. In the latter, abstinence rate was increased, 52.2% versus 31.03% ( p = .07) at M12. In patients both drinking and smoking, addiction treatment doubled the rate of abstinence of both products (31% vs. 14%).

Conclusion: Offering addiction treatment to patients with UADT cancer improves abstinence rate and helps maintain long-term withdrawal.
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http://dx.doi.org/10.3109/10826084.2013.821660DOI Listing
January 2014

Impact of tobacco and alcohol consumption in patients registered on waiting list on early morbidity following liver transplantation.

Clin Res Hepatol Gastroenterol 2013 Nov 20;37(5):473-8. Epub 2013 Mar 20.

Service d'addictologie, CHU Caremeau, place du Professeur-Robert-Debré, 30029 Nîmes, France.

Background: Liver transplantation (LT) is a high-risk surgery associated with postoperative complications. Smoking and drinking are known risk factors of long-term post-LT complications, but their role in early complications is still questioned.

Patients And Methods: We retrieved from our medical files the data of all patients registered for LT and who had had a consultation with a physician specialized in substance abuse. Consumption of alcohol, tobacco, and drugs before and after registration for LT was assessed.

Results: One hundred and five patients were included. Pre-registration smoking and drinking rates were 75.3 and 69.5%, respectively. Forty-three patients continued smoking and nine continued drinking until LT. Mortality and early morbidity rates were not impacted by smoking or drinking. Active smokers had significantly increased prevalence of bacterial cholangitis in comparison to patients who stopped smoking when registered for LT.

Conclusion: Persistent drinking in patients registered for LT is rare as compared to smoking; however, in our series, smoking until LT was not associated with major risk of early complication, except for cholangitis. This suggests that clinicians should take time to encourage patients to quit smoking and the intervention of a team specialized in substance abuse could be highly beneficial.
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http://dx.doi.org/10.1016/j.clinre.2013.01.009DOI Listing
November 2013

Iron overload in HFE C282Y heterozygotes at first genetic testing: a strategy for identifying rare HFE variants.

Haematologica 2011 Apr 12;96(4):507-14. Epub 2011 Jan 12.

Laboratoire d'Hématologie, CHU de Montpellier, Montpellier, France.

Background: Heterozygotes for the p.Cys282Tyr (C282Y) mutation of the HFE gene do not usually express a hemochromatosis phenotype. Apart from the compound heterozygous state for C282Y and the widespread p.His63Asp (H63D) variant allele, other rare HFE mutations can be found in trans on chromosome 6.

Design And Methods: We performed molecular investigation of the genes implicated in hereditary hemochromatosis in six patients who presented with iron overload but were simple heterozygotes for the HFE C282Y mutation at first genetic testing. Functional impairment of new variants was deduced from computational methods including molecular modeling studies.

Results: We identified four rare HFE mutant alleles, three of which have not been previously described. One mutation is a 13-nucleotide deletion in exon 6 (c.1022_1034del13, p.His341_Ala345 > LeufsX119), which is predicted to lead to an elongated and unstable protein. The second one is a substitution of the last nucleotide of exon 2 (c.340G > A, p.Glu114Lys) which modifies the relative solvent accessibility in a loop interface. The third mutation, p.Arg67Cys, also lies in exon 2 and introduces a destabilization of the secondary structure within a loop of the α1 domain. We also found the previously reported c.548T > C (p.Leu183Pro) missense mutation in exon 3. No other known iron genes were mutated. We present an algorithm at the clinical and genetic levels for identifying patients deserving further investigation. Conclusions Our results suggest that additional mutations in HFE may have a clinical impact in C282Y carriers. In conjunction with results from previously described cases we conclude that an elevated transferrin saturation level and elevated hepatic iron index should indicate the utility of searching for further HFE mutations in C282Y heterozygotes prior to other iron gene studies.
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http://dx.doi.org/10.3324/haematol.2010.029751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069226PMC
April 2011

Rituximab plus Peg-interferon-alpha/ribavirin compared with Peg-interferon-alpha/ribavirin in hepatitis C-related mixed cryoglobulinemia.

Blood 2010 Jul 3;116(3):326-34; quiz 504-5. Epub 2010 May 3.

Department of Internal Medicine, Assistance Publique-Hopitaux de Paris, Groupe Hospitalier Pitié-Salpétrière, Paris, France.

Treatment of hepatitis C (HCV)-mixed cryoglobulinemia (MC) may target either the viral trigger (HCV) or the downstream B-cell clonal expansion. Prospective cohort study of 38 HCV-MC patients who received a combination of rituximab (375 mg/m(2)) once a week for 1 month followed by Peg-interferon-alpha (Peg-IFN-alpha; 2a, 180 microg or 2b, 1.5 microg/kg) weekly plus ribavirin (600-1200 mg) daily for 48 weeks were compared with 55 HCV-MC patients treated by Peg-IFN-alpha/ribavirin with the same modalities. In the whole population of HCV-MC patients (n = 93), a complete clinical response was achieved in 73.1% (68 of 93), cryoglobulin clearance in 52.7% (49 of 93), and a sustained virologic response in 59.1% (55 of 93). Compared with Peg-IFN-alpha/ribavirin, rituximab plus Peg-IFN-alpha/ribavirin-treated patients had a shorter time to clinical remission (5.4 +/- 4 vs 8.4 +/- 4.7 months, P = .004), better renal response rates (80.9% vs 40% of complete response, P = .040), and higher rates of cryoglobulin clearance (68.4% vs 43.6%, P = .001) and clonal VH1-69(+) B-cell suppression (P < .01). Treatment was well tolerated with 11% of discontinuation resulting from antiviral therapy and no worsening of HCV RNA under rituximab. Our findings indicate that rituximab combined with Peg-IFN-alpha/ribavirin is well tolerated and more effective than Peg-IFN-alpha/ribavirin in HCV-MC.
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http://dx.doi.org/10.1182/blood-2009-10-248518DOI Listing
July 2010

The Southern French registry of genetic hemochromatosis: a tool for determining clinical prevalence of the disorder and genotype penetrance.

Haematologica 2010 Apr 9;95(4):551-6. Epub 2010 Feb 9.

CHU of Montpellier Laboratory of Hematology, Hôpital Saint Eloi, Avenue Augustin Fliche, 34295 Montpellier Cedex 5, France.

Background: Despite great progress in understanding the mechanisms underlying genetic hemochromatosis, data on the prevalence and the penetrance of the disorder are conflicting.

Design And Methods: A registry of patients with genetic hemochromatosis was established in the South of France and a regional health network was developed to allow the inclusion of all the diagnosed patients. C282Y homozygous patients classified in stages 2 (biological iron overload), 3 and 4 (clinical manifestations of iron overload, stage 4 being the more severe) according to the classification of the French National Authority for Health were included in the registry over a 6-year period.

Results: A total of 352 symptomatic C282Y homozygotes were identified, resulting in a total prevalence of 1.83 per 10,000 (95% CI: 1.63 to 2.02) in subjects over 20 years and 2.40 per 10,000 (95% CI, 2.15 to 2.65) among subjects of European descent. Among Europeans, the total calculated penetrance was 15.8% in stage 2 or higher, 12.1% in stage 3 or 4 and 2.9% in stage 4. The penetrance was slightly higher in males (18.7%) than in females (13.2%). It was 19.9% for individuals over 40 years of age (24.1% and 16.3% in males and females, respectively) with a maximum of 31% in subjects between 50 and 54 years old. Among 249 patients with complete records, 24% were in stage 2, the majority (58%) were in stage 3, and 18% in stage 4. There was a higher proportion of males, and excessive alcohol intake was more prevalent in stage 4 than in stages 2 and 3 combined.

Conclusions: A French Mediterranean regional hemochromatosis registry with strict inclusion criteria is a useful tool for characterizing the history of this disease, particularly for the most severely affected patients, as defined by the disease severity classification. The total prevalence of symptomatic C282Y homozygotes in the region was found to be low. However, clinical penetrance (stages 3 and 4) was not negligible.
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http://dx.doi.org/10.3324/haematol.2009.014431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857184PMC
April 2010

Efficacy and tolerability of rituximab with or without PEGylated interferon alfa-2b plus ribavirin in severe hepatitis C virus-related vasculitis: a long-term followup study of thirty-two patients.

Arthritis Rheum 2009 Aug;60(8):2531-40

Department of Internal Medicine, Groupe Hospitalier Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris (AP-HP), CNRS UMR 7211, and Université Pierre et Marie Curie Paris 6, Paris, France.

Objective: To report on the long-term followup of a cohort of patients with hepatitis C virus (HCV)-related vasculitis treated with rituximab with or without PEGylated interferon alfa-2b (PEG-IFN alfa-2b) plus ribavirin.

Methods: The study group comprised 32 HCV RNA-positive patients with HCV-related vasculitis: 20 patients were treated with rituximab and PEG-IFN alfa-2b (9 of whom had not previously received antiviral treatment and 11 of whom had experienced disease resistance to or relapse with antiviral treatment), and 12 antiviral-intolerant patients were treated with rituximab alone.

Results: Treatment with rituximab and PEG-IFN alfa-2b plus ribavirin induced a complete clinical response and a partial clinical response in 80% and 15% of patients, respectively, a complete immunologic response and a partial immunologic response in 67% and 33% of patients, respectively, and a sustained virologic response in 55% of patients. Treatment with rituximab alone induced a complete clinical response and a partial clinical response in 58% and 9% of patients, respectively, and a complete immunologic response and a partial immunologic response in 46% and 36% of patients, respectively. B cell depletion was achieved in 96% of patients, and B cell recovery began after a median delay of 12 months. After a mean+/-SD followup period of 23+/-12 months, 22% of patients experienced a clinical relapse, and 34% of patients experienced an immunologic relapse. All relapses were associated with the absence of virologic control, and 78% of relapses were associated with B cell recovery. Six patients were re-treated with rituximab. All 6 of these patients had a complete clinical response, 50% had a complete immunologic response, and 50% had a partial immunologic response. Rituximab was well tolerated overall.

Conclusion: Rituximab is an effective treatment of severe and/or refractory HCV-related vasculitis. Relapses were consistently associated with the absence of virologic control. The clinical and immunologic efficacy of rituximab after repeated infusion appeared to be the same as that observed after induction therapy.
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http://dx.doi.org/10.1002/art.24703DOI Listing
August 2009

CXCR3 expression on peripheral CD4+ T cells as a predictive marker of response to treatment in chronic hepatitis C.

Clin Immunol 2009 Jul 6;132(1):55-62. Epub 2009 May 6.

Service d'Addictologie, Hôpital Carémeau, Place du Pr Robert Debré, 30029 Nîmes cedex, France.

We monitored in fifty individuals with chronic hepatitis C (CHC) the expression of CCR5 and CXCR3, two chemokine receptors involved in the intra-hepatic recruitment of T cells, at the surface of circulating CD4+ T cells. The percentage of CD4+ T cells expressing CCR5 and/or CXCR3 was increased in patients. The increased percentage of CD4+ CXCR3+ T lymphocytes was linked to serum level of aspartate aminotransferase (AST) and to fibrosis METAVIR score. CD4+ T cell surface CCR5 and CXCR3 densities increased after 6 months of treatment with pegylated interferon-alpha and ribavirin. The pre-therapeutic percentage of CD4+ CXCR3+ T cells was correlated with alanine aminotransferase serum level at 12 months, and viral load at 24 months after treatment initiation. Thus, in CHC we observed a high CXCR3 expression on peripheral blood CD4+ T cells which correlates with AST serum level and liver fibrosis, and is predictive of the response to treatment.
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http://dx.doi.org/10.1016/j.clim.2009.03.521DOI Listing
July 2009

Testosterone deficiency: a common, unrecognized syndrome.

Nat Clin Pract Urol 2008 Jul;5(7):388-96

University of Saint Etienne Medical School, Saint Etienne, France.

Testosterone deficiency syndrome (TDS) refers to the clinical signs and symptoms that result from an abnormally low testosterone level. Men with 'classic' hypogonadism can have unequivocally low testosterone levels and typical symptoms and signs. By contrast, the age-related decline of testosterone levels can be responsible for ambiguous clinical pictures, which can potentially be misinterpreted as part of the aging process or depression. Nevertheless, this decline can have detrimental effects on quality of life and on the function of multiple organ systems. TDS is underdiagnosed-its overall prevalence varies from 6% to 9.5% in community-dwelling men aged 40-70 years, and rises to 15-30% in diabetic or obese men-and undertreated; less than 10% of men with TDS receive treatment. This Review highlights potential pitfalls in the diagnosis of both clinical and biochemical components of TDS.
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http://dx.doi.org/10.1038/ncpuro1167DOI Listing
July 2008

Global sequencing approach for characterizing the molecular background of hereditary iron disorders.

Clin Chem 2007 Dec 19;53(12):2060-9. Epub 2007 Oct 19.

Laboratory of Haematology, CHU of Montpellier, Montpellier, France.

Background: New genetic forms of hereditary hemochromatosis (HH) or hereditary hyperferritinemia (HF) have been identified over the last few years, and abnormalities of various genes may interact in a single patient. This study aimed to develop a rapid automated method for sequencing the main genes involved.

Methods: We used a standard 96-well microplate with a single PCR condition in an adaptation of the SCAIP (single-condition amplification with internal primer) method to sequence the HFE (hemochromatosis), HAMP (hepcidin antimicrobial peptide), HFE2/HJV [hemochromatosis type 2 (juvenile)], SLC40A1 (ferroportin), and TFR2 (transferrin receptor 2) genes, and the 5' untranslated region of the FTL (ferritin, light polypeptide) gene. To further simplify the method, we adjusted PCR conditions to avoid the use of an internal primer and applied this single-condition amplification method to 38 selected, unrelated patients. We tailored the genetic investigation according to the clinical picture, with the patients falling into 2 groups. Group 1 consisted of patients with hyperferritinemia and high transferrin saturation (TS) (classic adult and juvenile HH forms, groups 1A and 1B, respectively), and group 2 consisted of patients with hyperferritinemia and low, typical, or slightly increased TS, with or without iron overload (groups 2A and 2B, respectively).

Results: With this strategy we identified single-gene and multigene abnormalities, including 6 previously undescribed abnormalities in HFE (c.794dupA), HFE2 (c.-89-4dupT), and SLC40A1 (c.262A>G, c.533G>A, c.1468G>A, and c.-59_-45del).

Conclusion: This method is a simple approach for investigating hereditary iron overload or HF and allows rapid evaluation of patients.
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http://dx.doi.org/10.1373/clinchem.2007.090605DOI Listing
December 2007

Impact of hepatitis C virus (HCV) genotypes on quantification of HCV RNA in serum by COBAS AmpliPrep/COBAS TaqMan HCV test, Abbott HCV realtime assay [corrected] and VERSANT HCV RNA assay.

J Clin Microbiol 2007 Sep 20;45(9):3077-81. Epub 2007 Jun 20.

Unité Hépatites Virales, Laboratoire de Virologie, Hôpital Lapeyronie, av. du Doyen G. Giraud, 34295 Montpellier, France.

The VERSANT HCV RNA 3.0 (bDNA), COBAS AmpliPrep/COBAS TaqMan HCV, and Abbott ART HCV RealTime assays were compared for hepatitis C virus RNA quantification in 158 clinical specimens (genotypes 1 to 5). RNA values differed significantly between methods (P < 0.0001), and mean titer differences ranged from 0.01 to 0.50 log(10) IU/ml depending on the genotypes.
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http://dx.doi.org/10.1128/JCM.00111-07DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2045299PMC
September 2007

Initial endoscopic description of esophageal squamous cell carcinomas.

Gastroenterol Clin Biol 2006 Dec;30(12):1365-70

Service de Médecine Interne E, CHU Saint-Eloi, Montpellier.

Introduction: The aim of this study was to evaluate initial endoscopic practices at diagnosis of esophageal squamous cell carcinoma in comparison with current recommendations. We wanted to develop a standard model for the endoscopy report which could be used in routine practice.

Patients And Methods: From January 2000 to December 2002, 122 patients were hospitalized for esophageal squamous cell carcinoma. The initial endoscopic reports were reviewed retrospectively and compared with a model report established on the basis of current recommendations.

Results: One hundred and nineteen reports were re-examined. The principal reason for performing the endoscopic examination was dysphagia in 73.9% of patients. Tumor measurements (height, upper and lower extremities) were recorded in 51.2%, 79% and 41% of reports, respectively. 14.4% of the analyzed reports concerned endoscopic procedures which were performed after a first endoscopic examination because the initial report provided an imprecise tumor description. Tissue samples taken during the initial endoscopy allowed a pathological diagnosis in 94.2% of patients. Lugol staining was performed in 2.5% of procedures.

Conclusion: Insufficiently rigorous reporting compromises the reliability of initial upper digestive endoscopic procedures. Application of a standardized model for routine practice would favor more complete reports, starting with the first procedure.
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http://dx.doi.org/10.1016/s0399-8320(06)73556-4DOI Listing
December 2006

Hemodynamic changes induced by recreational scuba diving.

Chest 2006 May;129(5):1337-43

IMNSSA, B.P.610, 83800 Toulon, France.

Objective: Cardiac changes induced by scuba diving were investigated using Doppler echocardiography.

Material And Methods: Ten healthy scuba divers dove to a mean depth of 34.3 +/- 2.7 m of sea water (113 +/- 9 feet) and a mean duration of 25.3 +/- 3.5 min.

Results: One hour after the dive, microbubbles could be detected in the right-heart chambers of all subjects. Left atrial and left ventricular (LV) diameters significantly decreased after the dive. Cardiac output, assessed by aortic blood flow, remained unchanged. Heart rate increased and stroke volume (SV) decreased after the dive. LV filling was assessed on transmitral profile. An increase of the contribution of the atrial contraction to LV filling was observed. Right cavity diameters were unchanged, but an increase of the right ventricular/right atrial gradient pressure was found.

Conclusion: The diving profile studied promotes a rather important bubble grade in all volunteers. A significantly reduced cardiac diameters and SV was found by our hemodynamic study 1 h after diving. Two factors can explain these results: low volemia secondary to immersion, and venous gas embolism induced by nitrogen desaturation. Consequently, restoration of the water balance of the body should be considered in the recovery process after diving.
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http://dx.doi.org/10.1378/chest.129.5.1337DOI Listing
May 2006

Are preoperative patterns of alcohol consumption predictive of relapse after liver transplantation for alcoholic liver disease?

Transpl Int 2005 Nov;18(11):1292-7

Service de Médecine Interne E, Hôpital Saint Eloi, Montpellier cedex, France.

Predictive factors for alcoholic relapse after liver transplantation (LT) performed for alcoholic liver disease (ALD) have been assessed in numerous studies, often with contradictory results. The aim of the study was to assess pretransplantation alcohol consumption characteristics on alcoholic relapse after LT. Patients transplanted for ALD for at least 6 months were included. An anonymous questionnaire assessed socio-demographic characteristics, medical history, and alcohol consumption before and after LT. Relapse was defined as any alcohol use after LT. Severe relapse was defined by heavy drinking: more than 21 units/week for males and 14 units/week for females. A total of 61 patients were studied. The mean follow up after LT was 49 +/- 34 months. Alcoholic relapse occurred in 32 of 61 patients (52%) and severe relapse in eight of 61 patients (13%). Risk factors for severe relapse were: length of abstinence before LT (P = 0.0001), more than one alcohol withdrawal before LT (P = 0.001), alcohol dependence (P = 0.05), alcohol abuse in first relatives (P = 0.05), and younger age (P = 0.05). Information on previous alcohol consumption (dependence, number of withdrawals, family history) helps to predict severe relapse after LT in patients with ALD, allowing early awareness and specific postoperative care.
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http://dx.doi.org/10.1111/j.1432-2277.2005.00208.xDOI Listing
November 2005

Diminished CD4+ T cell surface CCR5 expression in alcoholic patients.

Alcohol Alcohol 2004 Nov-Dec;39(6):484-5. Epub 2004 Oct 21.

Service de Médecine Interne E, Hôpital Saint Eloi, 80 avenue Augustin Fliche, 34295 Montpellier cedex 5, France.

Aims: The C-C chemokine receptors, particularly the CCR5, appeared to play an important role in T cell-mediated inflammatory reactions. The aim of our study was to assess the impact of chronic alcohol consumption on the in vivo CCR5 expression.

Methods: Fourteen alcoholic men hospitalized for a detoxification programme were prospectively included and compared with 49 age-matched controls.

Results: The CD4(+) T cell surface CCR5 densities were drastically lower in alcoholic patients [mean, 5319 molecules/cell; 95% confidence interval (CI) 4477-6162] as compared with CCR5 densities of the controls (10 944 molecules/cell [CI 9929-11959]; P < 10(-4)).

Conclusions: Chronic alcohol consumption is associated with a significant decrease of CCR5 expression, which could favour Th1/Th2 imbalance.
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http://dx.doi.org/10.1093/alcalc/agh096DOI Listing
February 2005

Transitory ataxia related to topically administered lidocaine.

Ann Pharmacother 2004 May 23;38(5):828-30. Epub 2004 Mar 23.

Service de Médecine Interne E, Hôpital Saint Eloi, Faculté de Médecine de Montpellier, Montpellier, France.

Objective: To report 2 cases of transitory cerebellar ataxia related to lidocaine administered topically for endoscopy. case summaries: Two patients developed transitory cerebellar ataxia a few minutes after local anesthesia using lidocaine 10% spray and lidocaine 2% orally for a bronchoscopy and transesophageal echocardiography. This effect completely disappeared in 3-5 hours. In neither case was an alternate etiology of cerebellar ataxia identified. The second patient had previously experienced a similar reaction to lidocaine.

Discussion: Several central neurologic effects of lidocaine have been reported, but until now, only few cases of cerebellar ataxia. In these 2 cases, the Naranjo probability scale indicated that a probable and a highly probable relationship existed between lidocaine administration and the transitory cerebellar ataxia.

Conclusions: Cerebellar ataxia may occur after local anesthesia with lidocaine; therefore, care must be taken to avoid overdose, even when administered topically.
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http://dx.doi.org/10.1345/aph.1D494DOI Listing
May 2004

Specific alteration of peripheral cytotoxic cell perforin expression in alcoholic patients: a possible role in alcohol-related diseases.

Alcohol Clin Exp Res 2003 Nov;27(11):1825-30

Service de Médecine Interne, Laboratoire d'Immunologie, Hôpital Saint Eloi, Montpellier, France.

Background: The association between chronic alcohol consumption and an increasing risk of infectious and neoplastic disease is related to an impairment of cellular immunity. However, studies of the number and activity of lymphocyte subsets show highly variable results. The aim of this study was to assess the expression of perforin, one of the main molecular agents of T and natural killer (NK) cell-mediated cytotoxicity, in alcoholic patients without cirrhosis.

Methods: Eighteen patients with chronic alcoholism were prospectively included and compared with 18 age- and sex-matched healthy volunteers. Signs of hepatic insufficiency or portal hypertension, viral co-infection, other serious medical illness, and immune-related medications were exclusion criteria. Lymphocyte phenotype was assessed, and perforin expression was analyzed by flow cytometry in CD3+CD56+ T cells and NK cells. Granzyme synthesis was also evaluated in 11 of the 18 patients and compared with that of 11 age- and sex-matched controls.

Results: The mean number of white blood cells and lymphocytes was not different between the controls and alcoholic patients, whereas the mean number of NK cells was significantly decreased in alcoholic patients (110 +/- 79/mm3 versus 271 +/- 192/mm3; p < 0.03). Perforin expression in T CD3+/CD56+ and in NK cells was significantly decreased in alcoholic patients compared with controls: 16 +/- 3% vs. 36 +/- 4% (p < 0.03) and 65 +/- 15% vs. 78 +/- 9% (p = 0.04), respectively. The percentage of cells expressing granzyme was similar in both groups.

Conclusions: A decrease in perforin expression by cytotoxic cells could be a major factor in explaining the physiopathologic mechanisms of several alcohol-associated diseases.
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http://dx.doi.org/10.1097/01.ALC.0000093742.22787.30DOI Listing
November 2003

Are drugs a risk factor of post-ERCP pancreatitis?

Gastrointest Endosc 2003 Nov;58(5):696-700

Service de Médecine Interne E, Service d'Hépato-Gastroentérologie, Hôpital Saint Eloi, Montpellier Cedex 5, Montpellier, France.

Background: Pancreatitis is the most severe complication of ERCP. The aim of this study was to assess whether the use of potentially pancreatotoxic drugs is a risk factor for post-ERCP pancreatitis.

Methods: Risk factors for post-ERCP pancreatitis and all drugs taken during the month before ERCP were recorded retrospectively in a database. Patients with other causes of acute pancreatitis or chronic pancreatitis were excluded from the analysis. Post-ERCP pancreatitis was defined as abdominal pain and/or vomiting associated with amylase/lipase plasma levels equal to or greater than twice the upper normal value.

Results: A total of 173 patients (95 men, 78 women; mean age, 68 [16] years) were included. Post-ERCP pancreatitis occurred in 31 patients (18%). Several risk factors were identified in a multivariate analysis: difficulty in cannulation (p<0.001), endoscopic sphincterotomy (p<0.005), and female gender (p=0.02). Having taken potent pancreatotoxic drugs increased the occurrence of post-ERCP pancreatitis: odds ratio 3.7: 95% confidence intervals [1.1,12.4], p=0.04.

Conclusions: Use of pancreatotoxic drugs before or during ERCP significantly increased the risk of post-ERCP pancreatitis. Thus, discontinuation of the use of such drugs before ERCP seems justified whenever possible.
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http://dx.doi.org/10.1016/s0016-5107(03)02019-4DOI Listing
November 2003

[One-stage laparoscopic bilateral upper pole nephrectomy for ectopic insertion of complete ureteral duplication].

Prog Urol 2003 Apr;13(2):342-5

Service d'Urologie-Andrologie, Hôpital Nord, 42055 Saint Etienne.

Ectopic ureteric insertion of the superior renal unit in the context of complete ureteric duplication is frequently accompanied by destruction of the corresponding parenchymal territory. Surgical treatment must comprise upper pole nephrectomy with partial ureterectomy. The authors report a case of one-stage retroperitoneal laparoscopic bilateral treatment which could become the treatment of choice of this disease.
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April 2003

Nitrous oxide reverses the increase in striatal dopamine release produced by N-methyl-D-aspartate infusion in the substantia nigra pars compacta in rats.

Neurosci Lett 2003 Jun;343(2):147-9

Université de la Méditerranée, E.A. 3280, Laboratoire de Physiopathologie et Action Thérapeutique des Gaz sous Pression, Faculté de Médecine Nord, IFR Jean Roche, 13916 Marseilles Cedex 20, France.

Bilateral administration of NMDA (5 x 10(-10) mol) in the substantia nigra pars compacta increases the striatal dopamine (DA) release. However, this enhancing effect of NMDA was suppressed by nitrous oxide exposure at 0.1 MPa, which induced per se a decrease of the DA release. These results show that nitrous oxide exerts a reversal effect on the increase in striatal DA release produced by NMDA receptor activation in the substantia nigra pars compacta. This observation may be related to the fact that nitrous oxide is thought to produce its effects by acting as an NMDA receptor antagonist.
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http://dx.doi.org/10.1016/s0304-3940(03)00340-9DOI Listing
June 2003

Striatal dopamine release and biphasic pattern of locomotor and motor activity under gas narcosis.

Life Sci 2003 May;72(24):2731-40

Université de la Méditerranée et IMNSSA, E.A. 3280, Laboratoire de Physiopathologie et Action Thérapeutique des Gaz sous Pression, Faculté de Médecine Nord, IFR Jean Roche, 13916, cedex 20, Marseille, France.

Inert gas narcosis is a neurological syndrome appearing when humans or animals are exposed to hyperbaric inert gases (nitrogen, argon) composed by motor and cognitive impairments. Inert gas narcosis induces a decrease of the dopamine release at the striatum level, structure involved in the regulation of the extrapyramidal motricity. We have investigated, in freely moving rats exposed to different narcotic conditions, the relationship between the locomotor and motor activity and the striatal dopamine release, using respectively a computerized device that enables a quantitative analysis of this behavioural disturbance and voltammetry. The use of 3 MPa of nitrogen, 2 MPa of argon and 0.1 MPa of nitrous oxide, revealed after a transient phase of hyperactivity, a lower level of the locomotor and motor activity, in relation with the decrease of the striatal dopamine release. It is concluded that the striatal dopamine decrease could be related to the decrease of the locomotor and motor hyperactivity, but that other(s) neurotransmitter(s) could be primarily involved in the behavioural motor disturbances induced by narcotics. This biphasic effect could be of major importance for future pharmacological investigations, and motor categorization, on the basic mechanisms of inert gas at pressure.
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http://dx.doi.org/10.1016/s0024-3205(03)00183-8DOI Listing
May 2003