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Biomedical subjects

Marc Barthet

Publications and source records attributed to Marc Barthet.

At least 19 recordsLinked to original sources
PubMed2006

Peroxisome proliferator-activated receptor gamma agonist reduces the severity of post-ERCP pancreatitis in rats.

AIM: To determine the effects of prophylactic peroxi-some proliferator-activated receptor (PPARgamma) agonist administration in an experimental model of post-endoscopic retrograde cholangiopancreatography (post-ERCP) acute pancreatitis. METHODS: Post-ERCP pancreatitis was induced in male Wistar rats by infusion of contrast medium into the pancreatic duct. In additional group, rosiglitazone, a PPARgamma agonist, was administered 1 h before infusion of contrast medium. Plasma and pancreas samples were obtained 6 h after the infusion. RESULTS: Infusion of contrast medium into the pan-creatic duct resulted in an inflammatory process characterized by increased lipase levels in plasma, and edema and myeloperoxidase activity (MPO) in pancreas. This result correlated with the activation of nuclear factor kappaB (NFkappaB) and the inducible NO synthase (iNOS) expression in pancreatic cells. Rosiglitazone reduced the increase in lipase and the level of edema and the increase in myeloperoxidase as well as the activation of NFkappaB and iNOS expression. CONCLUSION: A single oral dose of rosiglitazone, given 1 h before post-ERCP pancreatitis induction is effective in reducing the severity of the subsequent inflammatory process. The protective effect of rosiglitazone was associated with NFkappaB inhibition and the blockage of leukocyte infiltration in pancreas.

Acute Disease↗
PubMed2006

Frequency and characteristics of pancreatitis in patients with inflammatory bowel disease.

BACKGROUND AND AIMS: Clinical symptoms of inflammatory bowel disease (IBD)-associated pancreatitis are found in approximately 2% of patients, but the frequency of the disease could be much higher since IBD-associated pancreatitis could be mainly a silent disease. The aim of this study was to describe the radiological and biological features of IBD-associated pancreatitis and assess its frequency by comparing data from IBD patients with or without a history of pancreatitis. METHODS: 79 patients were prospectively enrolled (median age 36 years). Symptoms of pancreatitis had been previously recorded in 30 of them (group P; the other 49 patients (group C) had no history of pancreatitis. Pancreatic ductal changes were investigated by pancreato-MRI. Exocrine function was assessed by the fecal elastase test and by assaying serum amylase, lipase, C-reactive protein, PAP, IgG4 and pancreatic autoantibodies. RESULTS: Increased levels of amylase and lipase occurred in 11% of IBD patients, that frequency being significantly higher in group P (23%) than in group C (4%) (p = 0.01). Low fecal elastase reflecting impaired exocrine function was observed in 30% of patients and again significantly more in group P (50%) than in group C (17%) (p = 0.04). The frequency of elevated values varied from 12% for amylase and lipase to 18% for PAP, 20% for pancreatic autoantibodies and 45% for CRP, without a difference between groups P and C. Silent exocrinopathy was observed in both groups, pancreatic autoantibodies and pancreatic duct alterations being found in 20 and 11% of patients, respectively. CONCLUSION: Finding pancreatic insufficiency in about 30% of the included patients and in 50% of those with a previous history of pancreatitis suggests that IBD might be associated with chronic pancreatic alteration. Episodes of mild acute pancreatitis observed in some patients are not always due to adverse effects of treatments and can be acute manifestations of the chronic disease.

Adult↗
PubMed2006

p8 is a new target of gemcitabine in pancreatic cancer cells.

Gemcitabine is the only available chemotherapeutic treatment of pancreatic cancers. It is, however, moderately effective, showing a tumor response rate of only 12%. The aim of this work was to identify new pathways involved in the resistance of pancreatic cancer cells to gemcitabine, in the hope of developing new adjuvant strategies to enhance its therapeutic efficacy. Comparison of gene expression patterns of five human pancreatic cancer cell lines showing different degrees of resistance to gemcitabine revealed specific overexpression of several genes in the most resistant. One of them encoded the antiapoptotic p8 protein. We found that (a) knocking down p8 expression in gemcitabine-resistant cells promoted cell death and increased caspase-3 activity; (b) forced overexpression of p8 in gemcitabine-sensitive cells increased their resistance to gemcitabine-induced apoptosis; and (c) gemcitabine down-regulated p8 mRNA expression. These results suggest that, in pancreatic cancer cells, a large part of gemcitabine-induced apoptosis results from the inhibition of the constitutive antiapoptotic activity of p8. Hence, targeting the p8-associated pathway could be a new adjuvant therapy improving the response of patients with pancreatic cancer to gemcitabine treatment.

Antimetabolites, Antineoplastic↗
PubMed2005

Diagnostic criteria in predicting a biliary origin of acute pancreatitis in the era of endoscopic ultrasound: multicentre prospective evaluation of 213 patients.

BACKGROUND: No study on bioclinical criteria predicting a biliary origin for acute pancreatitis has included endosonography as a reference examination. Re-examination of bioclinical parameters deserves consideration in the era where other causes are known (e.g. hereditary, autoimmune). AIM AND METHODS: To determine the performance of bioclinical markers in predicting a biliary origin of acute pancreatitis where the diagnosis of biliary lithiasis was established or ruled out using endosonography. Only patients with a first acute episode of pancreatitis were included. RESULTS: 213 patients (male: 55%; median age: 56 years) were prospectively included in 14 centres. Causes of acute pancreatitis were: biliary (62%), alcoholic (25%), other (13%). Delay between symptom-onset and admission was <48 h in 80%. Endosonography was the sole method establishing the diagnosis of biliary pancreatitis in 15% of patients. At univariate analysis, age, female sex, declared alcohol consumption, elevated aspartate and alanine transaminases on admission, gammaglutamyl transferase, alkaline phosphatase, total bilirubin, lipase, mean corpuscular volume were predictive of a biliary origin. Only age (p < 0.0001), sex (p < 0.0008) and alanine transaminase (p < 0.0004) remained significant at multivariate analysis. At age 50, the respective sensitivity and specificity were 73 and 65%. With an elevated alanine transaminase at 2 times the upper limit of normal range, the respective sensitivity and specificity were 74 and 84%. The probability of a biliary origin of acute pancreatitis could be estimated by the following formula: = 1/1 + exp(4.6967 - 0.0656 x age + 1.1208 x sex - 0.6909 x alanine transaminase). CONCLUSION: When endosonography is performed to confirm or exclude a biliary origin of acute pancreatitis, age, sex and alanine transaminase at admission are the only factors predictive of a biliary cause.

Acute Disease↗
PubMed2004

The substitution of endoscopic ultrasonography for endoscopic retrograde cholangio-pancreatography: implications for service development and training.

Diagnostic indications of endoscopic retrograde cholangio-pancreatography (ERCP) have not completely disappeared. But the substitution of this examination by endoscopic ultrasonography (EUS) in the work-up of biliary and pancreatic diseases is supported by EUS's reliability and cost-effectiveness. In the future EUS will be challenged by magnetic resonance cholangiopancreatography (MRCP), when easily available. Therefore, the choice between EUS, MRCP and ERCP will become simplified: MRCP as the first option for diagnosis, EUS in doubtful cases needing sampling for pathology and ERCP as a therapeutic alternative to some surgical procedures.

Bile Duct Diseases↗
PubMed2004

Autoimmune pancreatitis: increasing evidence for a clinical entity with various patterns.

Autoimmune pancreatitis is a clinical entity with many different clinical and biological characteristics that make diagnosis difficult. Sensitive and specific pancreatic antibodies are still lacking to assess the diagnosis as is the availability of interpretable pathological specimens. However, suggestive features consist mainly of radiological findings and clinical anomalies, particularly if there are associated autoimmune-related diseases. The immunological pathway is probably of cell-mediated origin, although various autoantibodies, insensitive and non-specific, may exist. Finally, many studies are needed to define more efficient diagnostic criteria and to discover the true prevalence of autoimmune pancreatitis.

Autoantibodies↗
PubMed2003

Mice with targeted disruption of p8 gene show increased sensitivity to lipopolysaccharide and DNA microarray analysis of livers reveals an aberrant gene expression response.

BACKGROUND: p8 is a DNA-binding protein induced in many tissues in response to LPS treatment. Hence, p8 could be a mediator of LPS-associated effects or, on the contrary, p8 expression may be part of the protective mechanism of the tissues in response to LPS. Finally, p8 expression in response to LPS could also be a simple epiphenomenon. METHODS: To investigate the role of p8 in vivo, we generated p8-deficient mice by gene targeting. Because p8 is a stress protein, we analyzed the response of p8-/- mice to a systemic stress induced by LPS injection. Liver was chosen as model organ to monitor alterations in gene expression. RESULTS: LPS resulted in higher serum TNF-alpha concentration and higher mortality rate in p8-deficient mice than in wild-type. Also, liver and pancreas, but not lung, from p8-/- mice showed increased amounts of MPO and HPO. To gain insight into the molecular bases of such susceptibility, we used high density DNA microarrays consisting of ~6000 genes and ESTs to compare gene regulation in response to LPS in p8+/+ and p8-/- livers. In wild-type, 105 genes and 73 ESTs were up-regulated and 232 genes and 138 ESTs down-regulated. By contrast, 212 genes and 125 ESTs were found up-regulated and 90 genes and 85 ESTs down regulated in p8-/- mice. Among them, only 93 (51 induced and 42 repressed) corresponded to the wild-type pattern, demonstrating that p8 deficiency hinders the normal response to LPS, which may account for the increased sensitivity of p8-/-mice to the endotoxin. CONCLUSIONS: The large number of genes showing abnormal regulation after LPS suggests that p8 is an important regulatory factor involved in many cellular defence pathways.

Animals↗
PubMed2003

Pancreatic changes in TNBS-induced colitis in mice.

BACKGROUND AND AIM: Recent clinical data suggest that pancreatitis could be an extraintestinal manifestation of inflammatory bowel disease. However, no experimental data support such a clinical relationship. The aim of this study was to investigate the presence of pancreatic damages in mice with TNBS-induced colitis. METHODS: Colitis was induced in Balb/C mice by intrarectal instillation of TNBS. Control mice received either intrarectal instillation of NaCl saline solution or 50% ethanol. Presence of colitis was assessed by macroscopic and microscopic examination, extent of mucosal damage being evaluated by the scoring systems of Wallace and Ameho in 8 mice with TNBS-induced colitis and in 4 controls. Pancreatic samples from the same mice underwent morphological examination after standard coloration. Intrapancreatic expression of the pancreatitis-associated protein (PAP), a marker of pancreatic inflammation, was monitored by automated immunohistochemistry using specific antibodies. In addition, quantification of TNFalpha mRNA by competitive PCR and semi-quantification of PAP, IL-10 and IL-1B mRNAs were performed on pancreas in 10 mice with TNBS-induced colitis and in 10 control mice. RESULTS: All mice treated with TNBS and none of the controls had colitis. Macroscopic and microscopic examination of the pancreas of the 4 control mice was normal, whereas in 5 out of the 8 TNBS-treated mice histological changes were observed, with inflammatory infiltrate and fibrin aggregates at the periphery of the gland. PAP immunohistochemistry was negative in all control mice and positive in all mice with TNBS-induced colitis, with a patchy distribution of staining. PAP immunolocalized to the cytoplasm of acinar cells, duct cells and islets of Langherans being negative. PAP and IL-1B mRNA levels in the pancreas were significantly increased but the increase in TNFalpha mRNA level did not reach statistical significance (P=0.06). IL-10 mRNA levels did not show any significant modification. CONCLUSION: PAP overexpression in pancreas demonstrates that inflammatory stress early occurs in the mouse pancreas during the course of TNBS-induced colitis. The concomitant pancreatic overexpression of IL-1B and, to a lesser extent, of TNFalpha, two proinflammatory cytokines also associated with the intestinal lesions of colitis, supported a pancreatic inflammatory mechanism mediated by cytokines.

Animals↗
PubMed2002

Long-term results of endoscopic management of pancreas divisum with recurrent acute pancreatitis.

BACKGROUND: The long-term efficacy of endoscopic treatment in pancreas divisum is controversial. This study evaluated the long-term results of dorsal duct stent insertion and endoscopic sphincterotomy of the minor papilla in patients presenting with recurrent acute pancreatitis or chronic pain. METHODS: Pancreas divisum was diagnosed in 175 patients between 1980 and 1998. Twenty-four patients seen with recurrent acute pancreatitis without underlying chronic calcifying pancreatitis or significant alcohol consumption were included in this study with a follow-up of at least 24 months. Eight were treated by sphincterotomy of the minor papilla alone, and 16 underwent dorsal duct stent insertion for a median duration of 8 months. RESULTS: The median duration of follow-up after endoscopic management was 39 months (range 24-105; interquartile range 40.5). All patients had recurrent acute pancreatitis before endoscopic treatment during a median period of 5 years. At the end of the follow-up there were only 2 recurrences of acute pancreatitis (p < 0.01). The number of patients with chronic pain before endoscopic treatment and at the end of follow-up decreased from 20 of 24 (83%) to 7 of 24 (29%) without reaching statistical significance. The 25% recurrence rate was estimated at 50 months by Kaplan-Meier analysis. Nine patients presented with a dilated dorsal duct before endoscopic treatment. After stent insertion, dorsal duct dilatation appeared in all 16 patients who underwent stent placement, and pancreatic duct stenosis developed in 3. Four patients (19%) required further treatment for pain recurrence or acute pancreatitis, with surgical procedures being performed in 2 cases. Complications occurred in 9 of 24 patients (38%), mainly acute pancreatitis or stenosis of the minor papilla. All complications except one were managed conservatively. Complications seemed to be less frequent after minor papilla sphincterotomy than after pancreatic stent insertion (25% vs. 44%). CONCLUSION: In patients with pancreas divisum, both dorsal duct stent insertion and minor papilla sphincterotomy decrease the rate of recurrent acute pancreatitis, whereas relief of chronic pain was less obvious.

Acute Disease↗
PubMed2002

Serum measurements of pancreatitis associated protein in active Crohn's disease with ileal location.

BACKGROUND AND AIMS: Pancreatitis-associated protein (PAP) is a pancreatic stress protein also expressed in the ileum but not in the colon. Its serum concentration is increased in patients with small bowel inflammation due to untreated celiac disease. We searched to determine whether PAP could be a serum marker for ileal location of active Crohn's disease (CD). METHODS: A multicenter prospective study was conducted, including 54 healthy controls and 124 patients with CD of whom 38 had quiescent ileal or ileocolonic disease (group A), 45 had active ileal or ileocolonic disease (group B), 18 had quiescent colon-only CD (group C), and 28 had active colonic disease (group D). Active disease was defined by a Crohn's disease activity index > 150 and serum C-reactive protein (CRP) > 10 mg/mL. Location of lesions was assessed by endoscopy. PAP was assayed in serum, the upper threshold for normal values being 50 ng/mL. RESULTS: In group B, 27 patients (60%) had elevated serum PAP, compared to one in group A (2.5%), one in group C (5.3%), three in group D (10.7%) and none in the control group (P<0.01). By contrast, serum levels of C-reactive protein did not differ between patients with active CD and either ileal location (group B) or pure colonic location (group D) (38 +/-10.5 vs 41.6 +/- 6.4 mg/mL, NS). Within group B, serum PAP concentration was correlated with none of the epidemiological, clinical or biological data available. Increased serum level of PAP diagnosed ileal location in active CD with a sensitivity of 60%, a specificity of 94%, a positive predictive value of 84% and a negative predictive value of 81%. CONCLUSION: Elevated serum PAP (> 50 ng/mL ) is significantly associated with disease activity and ileal location

Acute-Phase Proteins↗
PubMed2002

[Endoscopic management of biliary and pancreatic ascariasis in Viet-Nam. Report of a series of 91 cases].

AIM: Ascariasis is the most widespread helminthiasis in the world. Biliary and pancreatic involvement, frequently encountered in endemic areas, is a serious public health problem. Surgical management is often required. The purpose of our work was to assess the feasibility of emergency endoscopic treatment of biliary and pancreatic ascariasis in the Viet Duc hospital (Hanoi, Vietnam), and to evaluate outcome. METHODS: A prospective study conducted over a 3-year period included 91 patients with biliary and pancreatic ascariasis. Diagnosis was based on clinical findings and abdominal ultrasound and was confirmed by endoscopic procedures. RESULTS: The 91 patients, 21 males and 70 females, mean age 41 +/- 17 years, underwent endoscopic procedures to retrieve the worm. The procedure was successful in 89 patients (97.8%). Mild pancreatitis occurred in four patients who underwent biliary sphincterotomy. The mean hospital stay was 3.1 days. CONCLUSION: Endoscopic management of ascariasis is feasible, with a very low morbidity and a high rate of success. With this treatment, hospital stay is greatly shortened.

Adolescent↗