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Experimental evidence of obesity as a risk factor for severe acute pancreatitis

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World Journal of Gastroenterology 2009年第42期15卷 5260-5265页

作者： jean-louis frossard Pierre Lescuyer Catherine M Pastor Service of Gastroenterology Geneva University HospitalsGeneva 1205Switzerland Laboratory of pathophysiology and molecular imaging Geneva University HospitalsGeneva 1205Switzerland Service of Genetics and Central Laboratory Geneva University HospitalsGeneva 1205Switzerland

The incidence of acute pancreatitis,an inflammation of the pancreas,is increasing *** injury is mild in 80%-90% of patients who recover without *** remaining patients may develop a severe disease with local complications such as acinar cell necrosis,abscess and remote organ injury including lung *** early prediction of the severity of the disease is an important goal for physicians in management of patients with acute pancreatitis in order to optimize the therapy and to prevent organ dysfunction and local *** that purpose,multiple clinical scale scores have been applied to patients with acute ***,a new problem has emerged:the increased severity of the disease in obese ***,the mechanisms by which obesity increases the severity of acute pancreatitis are *** hypotheses have been suggested:(1) obese patients have an increased inflammation within the pancreas;(2) obese patients have an increased accumulation of fat within and around the pancreas where necrosis is often located;(3) increase in both peri-and intra-pancreatic fat and inflammatory cells explain the high incidence of pancreatic inflammation and necrosis in obese patients;(4) hepatic dysfunction associated with obesity might enhance the systemic inflammatory response by altering the detoxification of inflammatory mediators;and(5) ventilation/perfusion mismatch leading to hypoxia associated with a low pancreatic flow might reduce the pancreatic oxygenation and further enhance pancreatic *** experimental investigations also show an increased mortality and morbidity in obese rodents with acute pancreatitis and the implication of the adipokines lep-tin and *** models are important to investigate whether the inflammatory response of the disease is enhanced by *** is exciting to speculate that manipulation of the adipokine milieu has the potential to influence the severity of acute pancreatiti

关键词：急性胰腺炎治疗临床检查

Clopidogrel and proton pump inhibitors-where do we stand in 2012?

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World Journal of Gastroenterology 2012年第18期18卷 2161-2171页

作者： Michael D Drepper Laurent Spahr jean louis frossard Division of Gastroenterology Department of Internal MedicineGeneva University Hospital14 Geneva CH-1211Switzerland

Clopidogrel in association with aspirine is considered state of the art of medical treatment for acute coronary syndrome by reducing the risk of new ischemic *** treatment with proton pump inhibitors in order to prevent gastrointestinal side effects is recommended by clinical *** needs metabolic activation predominantly by the hepatic cytochrome P450 isoenzyme Cytochrome 2C19(CYP2C19) and proton pump inhibitors(PPIs) are extensively metabolized by the CYP2C19 isoenzyme as *** pharmacodynamic studies investigating a potential clopidogrel-PPI interaction found a significant decrease of the clopidogrel platelet antiaggregation effect for omeprazole,but not for *** clinical cohort studies in 2009 reported an increased risk for adverse cardiovascular events,when under clopidogrel and PPI treatment at the same *** observations led the United States Food and Drug Administration and the European Medecines Agency to discourage the combination of clopidogrel and PPI(especially omeprazole) in the same *** contrast,more recent retrospective cohort studies including propensity score matching and the only existing randomized trial have not shown any difference concerning adverse cardiovascular events when concomitantly on clopidogrel and PPI or only on *** meta-analyses report an inverse correlation between clopidogrel-PPI interaction and study quality,with high and moderate quality studies not reporting any association,rising concern about unmeasured confounders biasing the low quality ***,no definite evidence exists for an effect on *** PPI induced risk reduction clearly overweighs the possible adverse cardiovascular risk in patients with high risk of gastrointestinal bleeding,combination of clopidogrel with the less CYP2C19 inhibiting pantoprazole should be recommended.

关键词：质子泵抑制剂氯吡格雷 CYP2C19基因细胞色素P450 心血管疾病急性冠脉综合征代谢活化奥美拉唑

High prevalence of cholestasis, with increased conjugated bile acids in inflammatory bowel diseases patients

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World Journal of Clinical Cases 2018年第4期6卷 44-53页

作者： Marc Girardin Antoine Hadengue jean-louis frossard Service of Gastroenterology and Hepatology Geneva University Hospital

AIM To investigate the prevalence and causes of cholestasis in patients with inflammatory bowel diseases in the Swiss Inflammatory Bowel Diseases Cohort. METHODS A retrospective cohort study was performed of all the patients in the Swiss Inflammatory bowel disease Cohort. Total bile acid was measured for all patients and cholestasis was defined as a concentration > 8 μmol/L. The characteristics of patients with or without cholestasis were compared. Bile acid profiles were then determined for 80 patients with high total bile acid and 80 matched patients with low total bile acid. Bile acid profiles were compared for smokers vs nonsmokers, ileal vs colonic disease, and inflammatory vs non inflammatory *** Ninety-six patients had more than 8 μmol/L total bile acid, giving a prevalence of 7.15%. Patients with an obvious cause of cholestasis, such as primary sclerosing cholangitis, were then excluded, leaving 1190 participants with total bile acid 8 μmol/L. In multivariate analysis, calcium supplementation was significantly associated with cholestasis(odds ratio, 2.36, 95%CI: 1.00-5.21, P = 0.040) whereas current smoking significantly reduced the risk of cholestasis(odds ratio, 0.42, 95%CI: 0.17-0.91, P = 0.041). Levels of all conjugated bile acids were higher in the cholestasis group than in the control group. When we compared patients with ileal vs colonic disease, the former had higher levels of primary, secondary, and tertiary bile acids whereas patients with colonic disease had higher levels of conjugated bile *** Prevalence of cholestasis is high. Smoking appears to reduce cholestasis. Conjugated bile acids are higher in cholestasis and in colonic disease whereas unconjugated in ileal disease.

关键词： Lipid Liver Crohn’s disease Ulcerative colitis Cholestasis

Recent advances in gastrointestinal cancers

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World Journal of Gastroenterology 2021年第28期27卷 4493-4503页

作者： Natacha Bordry Christoforos Astaras Marie Ongaro Nicolas Goossens jean louis frossard Thibaud Koessler Department of Oncology University Hospital of Geneva(HUG)Genève 1205Switzerland Divison of Gastroenterology and Hepatology University Hospital of Geneva(HUG)Genève 1205Switzerland

Gastrointestinal cancers occur in a total of eight different locations,each of them with a different standard of *** article is not an exhaustive review of what has been published in *** have concentrated on the thirteen phase III randomized studies that are *** these studies are oral presentations which have been given in one of the four major oncology congresses,namely American Society of Clinical Oncology(ASCO),ASCO gastrointestinal(GI),European Society of Medical Oncology(ESMO)and *** provide a concise view of these major trials and their main outcomes,and put these results into context.

关键词： Practice changing trials Immunotherapy Gastrointestinal cancers Gastrointestinal Gastric cancer

Age,smoking and overweight contribute to the development of intestinal metaplasia of the cardia

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World Journal of Gastroenterology 2012年第17期18卷 2076-2083页

作者： Christian Felley Hanifa Bouzourene Marianne Bründler G VanMelle Antoine Hadengue Pierre Michetti Gian Dorta Laurent Spahr Emiliano Giostra jean louis frossard Service of Gastroenterology University Hospital1000 LausanneSwitzerland Institute of Pathology University Hospital1000 LausanneSwitzerland Institute of Social and Preventive Medicine University of Lausanne1000 LausanneSwitzerland Service of Gastroenterology Geneva University Hospital1211 GenevaSwitzerland

AIM:To assess the role of Helicobacter pylori(***),gastroesophageal reflux disease(GERD),age,smoking and body weight on the development of intestinal metaplasia of the gastric cardia(IMC).METHODS:Two hundred and seventeen patients scheduled for esophagogastroduodenoscopy were enrolled in this *** biopsies from the esophagus,gastroesophageal junction and stomach were evaluated for inflammation,the presence of *** and intestinal *** correlation of these factors with the presence of IMC was assessed using logistic ***:IMC was observed in 42% of the *** age,smoking habit and body mass index(BMI) were found as potential contributors to *** risk of developing IMC can be predicted in theory by combining these factors according to the following formula:Risk of IMC = a + s-2B where a = 2,…6 decade of age,s = 0 for non-smokers or ex-smokers,1 for 10 cigarettes/d and B = 0 for BMI 25 kg/m2(BMI > 27 kg/m2 in females).Among potential factors associated with IMC,*** had borderline signif icance(P = 0.07),while GERD showed no signif ***:Age,smoking and BMI are potential factors associated with IMC,while *** and GERD show no significant *** can be predicted in theory by logistic regression analysis.

关键词：吸烟者肠上皮年龄 Logistic回归分析 logistic回归幽门螺旋杆菌幽门螺杆菌超重

Scanning transmission electron microscopy and atom probe tomography analysis of non-stoichiometry long-period-stacking-ordered structures in Mg-Ni-Y/Sm alloys

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Journal of Magnesium and Alloys 2024年第3期12卷 954-965页

作者： Yimeng Chen Manuel Legrée jean-louis Bobet Alexander Kvit CAMECA Instruments Inc MadisonWI 53711USA ICMCB Universitéde BordeauxPessacCEDEX 33608France NIAC&Materials Science Department University of WisconsinMadisonWI 53706USA

The long-period-stacking-ordered(LPSO)structure affects the mechanical,corrosion and hydrolysis properties of Mg *** current work employs high angle annular dark field-scanning transmission electron microscopy(HAADF-STEM)and atom probe tomography(APT)to investigate the structural and local chemical information of LPSO phases formed in Mg-Ni-Y/Sm ternary alloys after extended isothermal *** on the alloying elements and their concentrations,Mg-Ni-Y/Sm develops a two-phase LPSO+α-Mg structure in which the LPSO phase contains defects,hybrid LPSO structure,and Mg ***-STEM and APT indicate non-stoichiometric LPSO with incomplete Ni_(6)(Y/Sm)_(8) *** addition,the APT quantitatively determines the local composition of LPSO and confirms the presence of Ni within the Mg bonding *** results provide insight into a better understanding of the structure and hydrolysis properties of LPSO-Mg alloys.

关键词： Magnesium alloys Long-range ordering Atom probe tomography(APT) STEM HAADF Hydrolysis properties.

Concomitant autoimmune and genetic pancreatitis leads to severe inflammatory conditions

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World Journal of Gastroenterology 2008年第16期14卷 2596-2598页

作者： jean louis frossard jean Marc Dumonceau Catherine Pastor Laurent Spahr Antoine Hadengue Division de Gastroentérologie et Hépatologie Geneva University Hospital

Chronic pancreatitis characterized by an early onset should be extensively investigated including the search for a mutation of the PRSS1, SPINK-1 or CFTR genes and potential features of autoimmune pancreatitis. We here describe a case of chronic pancreatitis with an onset at a very young age in which a mutation of the PRSS1 and several features of autoimmune pancreatitis were identified.

关键词：慢性胰腺炎遗传学 SPINK-1 CFTR PRSS1

Alcoholic pancreatitis:A tale of spirits and bacteria

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World Journal of Gastrointestinal Pathophysiology 2014年第2期5卷 82-90页

作者： Alain Vonlaufen Laurent Spahr Minoti V Apte jean-louis frossard Gastroenterology Unit Hopital de la Tour Department of Gastroenterology University Hospital Pancreatic Research Group South Western Sydney Clinical SchoolThe Ingham Institute Faculty of Medicine The University of New South Wales

Alcohol is a major cause of chronic ***5%of alcoholics will ever suffer from pancreatitis,suggesting that additional co-factors are required to trigger an overt *** work has implicated lipopolysaccharide,from gut-derived bacteria,as a potential co-factor of alcoholic *** review discusses the effects of alcohol on the gut flora,the gut barrier,the liver-and the pancreas and proposes potential interventional strategies.A better understanding of the interaction between the gut,the liver and the pancreas may provide valuable insight into the pathophysiology of alcoholic pancreatitis.

关键词： Alcohol Pancreatitis Fibrosis Bacteria Endotoxin Lipopolysaccharide

Endothelial nitric oxide synthase regulation is altered in pancreas from cirrhotic rats

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World Journal of Gastroenterology 2006年第2期12卷 228-233页

作者： jean-louis frossard Rafael Quadri Antoine Hadengue Philippe Morel Catherine M Pastor Division de Gastroenterologie Hpitaux Universitaires de Geneve Departement de Chirurgie Hopitaux Universitaires de Geneve Laboratoire de Physiopathologie Hepatique et Imagerie Moleculaire Hpitaux Universitaires de Geneve

瞄准：决定胆汁性肝硬变是否能在内皮的氮的氧化物 synthase (eNOS ) 导致象修正那样的胰腺的机能障碍表达式并且 eNOS 的规定是否能被规章的蛋白质 caveolin 改变并且加热吃惊蛋白质 90 (Hsp90 ) ，以及由对 eNOS 有约束力的 calmodul... 详细信息

瞄准：决定胆汁性肝硬变是否能在内皮的氮的氧化物 synthase (eNOS ) 导致象修正那样的胰腺的机能障碍表达式并且 eNOS 的规定是否能被规章的蛋白质 caveolin 改变并且加热吃惊蛋白质 90 (Hsp90 ) ，以及由对 eNOS 有约束力的 calmodulin 的修正。方法：Immunoprecipitations 和西方的弄污分析在从假冒、肝脏硬化症的老鼠孤立的胰被执行。结果：胰腺的损害在肝脏硬化症的老鼠是次要的，但是 eNOS 表示重要地与长度减少了(并且严厉) 疾病。因为有 Hsp90 和 caveolin 的 eNOS 的 co-immunoprecipitation 同样在肝脏硬化症的老鼠减少了， eNOS 活动没被这机制修改。相反，肝硬化减少了 calmodulin 绑定到有在 eNOS 的伴随物减少的 eNOS 活动。结论：在胆汁性肝硬变，胰腺的损害是次要的但是胰腺的氮的氧化物(没有) 生产被二机制显著地减少：酶和到 eNOS 的 calmodulin 的减少的绑定的减少的表情。

关键词：胰腺胆汁性肝硬变内皮NO合酶热休克蛋白大鼠