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Biomedical subjects

J Devière

Publications and source records attributed to J Devière.

At least 19 recordsLinked to original sources
PubMed2001

Interleukin 10 reduces the incidence of pancreatitis after therapeutic endoscopic retrograde cholangiopancreatography.

BACKGROUND & AIMS: Prophylactic administration of interleukin (IL)-10 decreases the severity of experimental pancreatitis. Prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis in humans is a unique model to study the potential role of IL-10 in this setting. METHODS: In a single-center, double-blind, randomized, placebo-controlled study, the effect of a single injection of 4 microg/kg (group 1) or 20 microg/kg (group 2) IL-10 was compared with that of placebo (group 0), all administered 30 minutes before therapeutic ERCP. The primary endpoint was the effect of IL-10 on serum levels of amylases and lipases measured 4, 24, and 48 hours after ERCP. The secondary objective was to evaluate changes in plasma cytokines (IL-6, IL-8, tumor necrosis factor) at the same time points and the incidence of acute pancreatitis in the 3 groups. Subjects undergoing a first therapeutic ERCP were eligible for inclusion. RESULTS: A total of 144 patients were included. Seven were excluded based on intention to treat (n = 1) or per protocol (n = 6). Forty-five, 48, and 44 patients remained in groups 0, 1, and 2, respectively. The 3 groups were comparable for age, sex, underlying disease, indication for treatment, type of treatment, and plasma levels of C-reactive protein (CRP), cytokines, and hydrolases at baseline. No significant difference was observed in CRP, cytokine, and hydrolase plasma levels after ERCP. Forty-three patients developed hyperhydrolasemia (18 in group 0, 14 in group 1, and 11 in group 2; P = 0.297), and 19 patients developed acute clinical pancreatitis (11 in group 0, 5 in group 1, 3 in group 2; P = 0.038). Two severe cases were observed in the placebo group. No mortality related to ERCP was observed. Logistic regression identified 3 independent risk factors for post-therapeutic ERCP pancreatitis: IL-10 administration (odds ratio [OR], 0.46; 95% confidence interval [95% CI], 0.22-0.96; P = 0.039), pancreatic sphincterotomy (OR, 5.04; 95% CI, 1.53-16.61; P = 0.008), and acinarization (OR, 8.19; 95% CI, 1.83-36.57; P = 0.006). CONCLUSIONS: A single intravenous dose of IL-10, given 30 minutes before the start of the procedure, independently reduces the incidence of post-therapeutic ERCP pancreatitis.

Abdominal Pain↗
PubMed2001

Argon plasma coagulation in the treatment of Barrett's high-grade dysplasia and in situ adenocarcinoma.

BACKGROUND AND STUDY AIMS: Endoscopic therapy of high-grade dysplasia (HGD) and superficial adenocarcinoma associated with Barrett's esophagus (BE), using Nd:YAG laser, KTP laser, or photodynamic therapy (PDT), has been reported to be effective in a curative role. Argon plasma coagulation (APC) appears to be effective in the eradication of nondysplastic Barrett's mucosa, but no results are available in the management of early neoplasms complicating BE. We report our initial experience in the application of APC in this indication. PATIENTS AND METHODS: Ten patients (mean age 74.2) with histologically proven HGD (n = 7) or in situ adenocarcinoma (n = 3) associated with BE (mean length 6 cm) and unfit for surgery were treated using APC and high-dose omeprazole (40 mg daily) until squamous re-epithelialization or complete eradication of the initially apparent lesions. Endoscopic follow-up was maintained at every 3 months. RESULTS: Complete eradication of HGD and in situ adenocarcinoma was achieved after a mean number of 3.3+/-1.5 APC sessions in 8/10 patients (80%). The eight patients with complete clearance of the neoplastic areas did not show any evidence of local recurrence during a median follow-up of 24 months (range 12-36 months). One patient with initial HGD had persistence of HGD 30 months after initial diagnosis, and one patient progressed to invasive adenocarcinoma after failure of APC and PDT. CONCLUSIONS: APC is safe and effective in the management of HGD and in situ adenocarcinoma associated with BE, and might represent an interesting alternative in selected patients who are not candidates for surgery.

Adenocarcinoma↗
PubMed2001

Pancreas divisum: evaluation with secretin-enhanced magnetic resonance cholangiopancreatography.

BACKGROUND: The clinical significance of pancreas divisum (PD) remains controversial. Secretin-enhanced magnetic resonance cholangiopancreatography (S-MRCP) is a noninvasive diagnostic procedure that relies on the dynamic response of the main pancreatic duct (MPD) to secretin stimulation. The aim of this study was to determine the frequency of PD and to analyze the dynamic changes of the MPD by using S-MRCP in patients referred for suspected pancreatic diseases before ERCP. METHODS: MRCP was obtained before and at 30-second intervals over 10 minutes after secretin stimulation in consecutive patients with idiopathic acute pancreatitis (n = 67), persistent hydrolasemia (n = 42), recurrent abdominal pain thought to be of pancreatic origin (n = 48), severe chronic pancreatitis (n = 68), and in a control group (n = 54). RESULTS: Thirty patients (10.8%) had a PD at S-MRCP. Secretin stimulation improved the detection of PD in 23% (7/30). The frequency of PD was not significantly different (p > 0.2) between these groups. The occurrence of an abnormal response at S-MRCP (persistent dilatation of the MPD) did not significantly differ in patients with or without PD (p > 0.4). CONCLUSION: The frequency of PD did not differ between groups, and the dynamic changes of the MPD during S-MRCP were similar in patients with and without PD.

Adolescent↗
PubMed2001

Prognostic value of hepatocyte proliferative activity after transjugular intrahepatic portosystemic shunt.

OBJECTIVES: Previous data indicated that the proliferating cell nuclear antigen-labeling index (PCNA-LI) reflects the liver functional reserve in human liver cirrhosis. The aim of the study was to evaluate the hepatocyte proliferative activity as a marker for the outcome of patients after transjugular intrahepatic portosystemic shunt (TIPS). METHODS: Twenty-eight consecutive patients were electively treated with TIPS for recurrent variceal bleeding (n = 14), refractory ascites (n = 12), or hydrothorax (n = 2). PCNA immunostaining was analyzed on methanol-fixed, paraffin-embedded liver biopsies. RESULTS: After TIPS, six patients died within the first 3 months, eight other patients died later, two were transplanted, and 12 were alive at the time of analysis. Early death occurred in patients with refractory ascites (5/12) and/or in Child C patients (3/6). Among the evaluated variables, there was a statistical trend for the PCNA-LI to be lower in patients who died early after TIPS than in those having long term survival (1.55% vs 2.65%, p = 0.07). After TIPS insertion, the probability of remaining alive during the first 6 months of follow-up was significantly higher in patients with a preprocedural PCNA-LI > 2.9%. CONCLUSIONS: The PCNA-LI measured on liver biopsy before the TIPS procedure might be a pre-TIPS marker to discriminate those patients for whom TIPS is likely to be beneficial.

Adult↗
PubMed2001

Metabolic handling of intraduodenal vs. intravenous glucose in humans.

To determine whether the route of glucose administration affects whole body glucose metabolism, 14 healthy volunteers were randomly infused with intraduodenal (id) or intravenous (iv) glucose at 6 mg x kg(-1) x min(-1) for 180 min. Infused glucose was labeled with [2-(3)H]glucose in a first series of paired experiments designed to characterize kinetic parameters to be used in a second series of experiments in which [3-(3)H]- and [U-(14)C]glucose labeling was used to characterize the metabolic fate of infused glucose. Experiments with [2-(3)H]glucose showed that, after a lag period of only 20 min, id absorption averaged 105 +/- 3% of infusion. During the final hour of id and iv infusion of [3-(3)H]glucose, tissue uptake averaged 98 +/- 3 and 107 +/- 4% of infusion, respectively, and was equally divided between glycolysis ((3)H(2)O production) and storage (uptake-glycolysis). Glucose oxidation ((14)CO(2)), total carbohydrate oxidation (indirect calorimetry), and net carbohydrate balance were also similar, but the thermic effect of glucose was significantly greater after id infusion. Because insulin and estimated portal vein glucose levels were similar during the final 80 min of both infusions, our results suggest that hepatic glucose storage (and therefore muscle storage estimated as whole body minus liver storage) is not affected by the route of glucose administration.

Adult↗
PubMed2000

Repeated concanavalin A challenge in mice induces an interleukin 10-producing phenotype and liver fibrosis.

Weekly injections of Concanavalin A (Con A) were performed in BALB/c mice to evaluate the pattern of cytokine production and liver injury. High serum levels of tumor necrosis factor alpha (TNF-alpha), interleukin 2 (IL-2), IL-4, and interferon gamma (IFN-gamma) were found in the serum after the first 2 injections of Con A but rapidly decreased from the third injection. Conversely, IL-10 serum levels after repeated Con A challenge increased by 7 times from week 1 to 20. In vivo depletion studies indicated that CD4(+) T cells are essential in IL-10 production. Hepatocyte necrosis was only observed after the first injections of Con A whereas centrilobular inflammatory infiltrates persisted up to 20 weeks. Perisinusoidal liver fibrosis was also increasingly detected in BALB/c mice, whereas no fibrous change was observed in nude mice after 6 weeks of Con A challenge. The number of stellate cells, detected by immunostaining, increased after 20 weeks of Con A injections. Liver cytokine messenger RNA (mRNA) expression after 20 weeks showed expression of transforming growth factor beta1 (TGF-beta1), IL-10, and IL-4 whereas IL-2 was no more expressed. The present study shows that mice repeatedly injected with Con A develop liver fibrosis. The cytokine-release pattern observed after 1 injection of Con A is rapidly shifted towards an immunomodulatory phenotype characterized by the systemic production of large amounts of IL-10.

Animals↗
PubMed2000

CD4(+ )T cells play an important role in acute experimental pancreatitis in mice.

BACKGROUND & AIMS: Few data are available on the potential role of T lymphocytes in experimental acute pancreatitis. The aim of this study was to characterize their role in the inflammatory cascade of acute pancreatitis. METHODS: To type this issue, acute pancreatitis was induced by repeated injections of cerulein in nude mice and in vivo CD4(+) or CD8(+) T cell-depleted mice. The role of T lymphocyte-costimulatory pathways was evaluated using anti-CD40 ligand or anti-B7-1 and -B7-2 monoclonal blocking antibodies. The role of Fas-Fas ligand was explored using Fas ligand-targeted mutant (generalized lymphoproliferative disease) mice. Severity of acute pancreatitis was assessed by serum hydrolase levels and histology. Intrapancreatic interleukin 12, interferon gamma, Fas ligand, and CD40 ligand messenger RNA were detected by reverse-transcription polymerase chain reaction. Intrapancreatic T lymphocytes were identified by immunohistochemistry. RESULTS: In control mice, T cells, most of them CD4(+) T cells, are present in the pancreas and are recruited during acute pancreatitis. In nude mice, histological lesions and serum hydrolase levels are significantly decreased. T-lymphocyte transfer into nude mice partially restores the severity of acute pancreatitis and intrapancreatic interferon gamma, interleukin 12, and Fas ligand gene transcription. The severity of pancreatitis is also reduced by in vivo CD4(+) (but not CD8(+)) T-cell depletion and in Fas ligand-targeted mutant mice. Blocking CD40-CD40 ligand or B7-CD28 costimulatory pathways has no effect on the severity of pancreatitis. CONCLUSIONS: T lymphocytes, particularly CD4(+) T cells, play a pivotal role in the development of tissue injury during acute experimental pancreatitis in mice.

Acute Disease↗
PubMed2000

Prevalence and clinical evolution of isolated ventral pancreatitis in alcoholic chronic pancreatitis.

BACKGROUND: The role of pancreas divisum in chronic pancreatitis is controversial. Ductal changes limited to the pancreatic ventral duct (isolated ventral pancreatitis) have only been described as isolated case reports. METHODS: In a cohort of 542 patients with chronic pancreatitis we determined the frequency of ventral chronic pancreatitis among patients with pancreas divisum and analyzed the clinical presentation of 10 patients with isolated ventral alcohol-induced pancreatitis compared with 10 patients with isolated dorsal alcohol-induced pancreatitis and 30 patients with chronic pancreatitis and without pancreas divisum. Magnetic resonance pancreatography under secretin stimulation was used to evaluate the status of the dorsal pancreatic duct in some patients during follow-up. RESULTS: We identified 62 (11.4%) patients with pancreas divisum and 16 (2.9%) patients with incomplete pancreas divisum. The ventral duct was affected by chronic pancreatitis in 74% of these patients. Isolated ventral or dorsal duct alterations were identified in 14% and 26%, respectively, of patients with pancreas divisum. Patients with isolated ventral pancreatitis had pain symptoms similar to those of the two other groups but had no endocrine or exocrine insufficiency on initial presentation. After a mean follow-up of 44 months, 83% of patients studied with isolated ventral pancreatitis developed alterations of the dorsal ductal part of the gland. CONCLUSION: We conclude that isolated ventral alcohol-induced pancreatitis is one of the first manifestations of generalized pancreatic disease where the anatomic factor of pancreas divisum plays only a marginal role.

Acute Disease↗
PubMed2000

Cold liver ischemia-reperfusion injury critically depends on liver T cells and is improved by donor pretreatment with interleukin 10 in mice.

Kupffer cells are thought to mediate most of the deleterious effects of liver ischemia-reperfusion injury. The role of liver T cells and the impact of resident cell deactivation by interleukin 10 (IL-10) have never been addressed. Using a model of ex vivo liver cold ischemia and reperfusion, we assessed liver injury, tumor necrosis factor (TNF) and interferon gamma (IFN-gamma) release from livers of balb/c mice, nude mice, nude mice reconstituted with T cells, and gadolinium balb/c pretreated mice. The anti-inflammatory cytokine IL-10 was then used to define the best strategy of administration potentially able to modulate ischemia-reperfusion injury. For this purpose IL-10 was administered to the donor before liver harvesting, in the preservation medium during cold ischemia or during reperfusion. TNF and IFN-gamma were released time dependently and paralleled liver injury after reperfusion of cold preserved livers. Reperfused livers from nude or gadolinium pretreated mice disclosed a dramatic decrease in TNF and IFN-gamma release. Tissue injury was reduced by 51% in the absence of T cells and by 88% when Kupffer cells were deactivated. This effect was reverted by T-cell transfer to nude mice. Only donor pretreatment with IL-10 or IL-10 infusion during reperfusion led to a significant decrease in liver injury, TNF, and IFN-gamma release (-66% or -41%, -95% or -94%, and -70% or -70%, respectively). In conclusion, liver resident T cells are critically involved in cold ischemia-reperfusion injury and pretreatment of the donor with IL-10 decreases liver injury and the release of T-cell- and macrophage-dependent cytokines.

Animals↗
PubMed2000

N-acetylcysteine decreases severity of acute pancreatitis in mice.

Oxidative stress plays a major role in the early stage of acute pancreatitis. This study assessed the effects of N-acetylcysteine (NAC), a reduced glutathione (GSH) provider and a direct scavenger of reactive oxygen intermediates, in the course of acute pancreatitis in mice. Acute pancreatitis (AP) was induced by intraperitoneal (i.p.) injections of cerulein. Mice received NAC (1,000 mg/kg, i.p.) every 3 h, starting either 1 h before the first cerulein injection (prophylactic group) or 1 h after the first cerulein injection (therapeutic group), or i.p. saline injections for controls. Severity of AP was evaluated by histology, serum hydrolase levels, and serum and intrapancreatic levels of MCP-1 and interleukin 6 (IL-6). Pancreatic conjugated dienes and intrapancreatic and intrahepatic GSH levels were measured to assess the local and systemic oxidative processes. Acute pancreatitis was also induced with a CDE diet in controls and mice receiving either both NAC ad libidum in drinking water and 1,000 mg/kg i.p. injection once daily. The severity of pulmonary lesions was assessed by arterial blood gases (pO2) and intrapulmonary myeloperoxidase (MPO content) measurements as well as the survival of mice. The severity of cerulein-induced AP was significantly decreased in the prophylactic group compared with the therapeutic and control groups. Prophylactic administration of NAC also decreased the intrapancreatic levels of conjugated dienes compared with controls. The intrapancreatic and systemic release of MCP- 1 and IL-6 was also decreased in the prophylactic group 3 and 6 hours after AP induction. In addition, NAC pretreatment also reduced hepatic IL-6 production at 3 and 6 hours after starting cerulein challenge. In CDE-induced AP, the severity of lung injury (hypoxemia, MPO content) was decreased, and survival was improved by NAC. NAC administered in a prophylactic protocol limits the severity of experimental acute pancreatitis in mice, as well as its systemic complications and related mortality.

Acetylcysteine↗
PubMed2000

Outcome after surgical resection of intraductal papillary and mucinous tumors of the pancreas.

OBJECTIVE: Treatment of intraductal papillary and mucinous tumors of pancreas (IPMT) usually requires surgery. The objective of this study was to evaluate the risk of recurrence in patients after surgery according to the histological nature of the neoplasm and the type of surgery. METHODS: The outcome of 45 patients who underwent partial pancreatectomy (n = 35) or total pancreatectomy (n = 10) for IPMT was studied according to the nature of the neoplasm (invasive carcinoma or noninvasive neoplasm), type of surgery (partial or total pancreatectomy), and lymph nodes status. RESULTS: The overall 3-yr actuarial survival rate was 83%. Death occurred in seven of 20 (35%) patients with invasive carcinoma and in one of 26 (4%) patients with noninvasive tumors (p<0.05). There were two recurrences in the seven patients with noninvasive neoplasm who underwent partial pancreatectomy with involved resection margins, and none in the 13 patients with disease-free margins. In patients with invasive carcinoma, there was one recurrence after total pancreatectomy, six after partial pancreatectomy with disease-free margins and six after partial pancreatectomy with involved margins. In patients with invasive carcinoma, total pancreatectomy and the absence of lymph nodes involvement were independently associated with a low risk of recurrence. CONCLUSIONS: IPMT may be managed as follows: 1) in patients with noninvasive neoplasms, partial pancreatic resection should be guided by frozen section examination until disease-free margins are obtained; and 2) in patients with invasive carcinoma, total pancreatectomy seems most likely to cure the patient, but should be discussed according to the general status and the age.

Actuarial Analysis↗
PubMed2000

A comparison of Ultraflex Diamond stents and Wallstents for palliation of distal malignant biliary strictures.

OBJECTIVE: The objective of this study was to compare the effectiveness of the Ultraflex Diamond stent and the Wallstent for the drainage of distal malignant biliary strictures. METHODS: The results obtained in 23 consecutive patients in whom the insertion of a Ultraflex Diamond stent had been attempted were compared with those obtained in 23 patients matched for age, gender, serum bilirubin, and diagnosis who had been treated with Wallstents. RESULTS: Biliary drainage was obtained in 100% of cases. More than one stent was required in 4% and 12% of patients treated with Ultraflex Diamond stents and Wallstents, respectively (p > 0.05). The first stent inserted did not provide adequate biliary drainage in four patients, because of the impaction of the proximal end of Wallstents into the bile duct wall (n = 2) and obstruction of the stent lumen by tumor tissue (one in each group). Procedure-related morbidity and mortality were 4%. Patients were followed-up for a mean of 228 days (range, 1 to 1262 days). During follow-up, bile duct obstruction relapsed in 5/22 and 6/21 patients treated with Ultraflex Diamond stents and Wallstents, respectively. Life table analysis of bile duct patency was similar with both stent models. CONCLUSIONS: Ultraflex Diamond stents are easy to insert and provide a high success rate of biliary drainage with minimal complication. Although long-term patency rates obtained with this stent were similar to those observed with Wallstents, no firm conclusion can be drawn in this regard due to the relatively small number of patients studied.

Adult↗
PubMed2000

Intramucosal adenocarcinoma arising under squamous re-epithelialisation of Barrett's oesophagus.

BACKGROUND: Eradication of Barrett's mucosa by thermal or photoablation combined with high doses of proton pump inhibitors is a potentially attractive strategy in the management of this preneoplastic condition. However, major concerns of this method are the persistence of residual metaplastic glands beneath the new squamous epithelium and the absence of any knowledge of its impact on long term outcome. CASE REPORT: The case of an intramucosal adenocarcinoma diagnosed 18 months after apparently complete squamous re-epithelialisation achieved using argon plasma coagulation and high dose omeprazole (40 mg/daily) is reported in a 68 year old patient presenting initially with a Barrett's oesophagus without dysplasia. Intramucosal adenocarcinoma was located under the new squamous layer and presented as a bulging area covered by the squamous epithelium. It probably originates from residual metaplastic glands after therapy although a pre-existing tumour cannot be definitely excluded. CONCLUSION: This observation might question future application of this experimental endotherapy in non-dysplastic Barrett's oesophagus. It suggests that the residual glands might still be premalignant and that the early diagnosis of neoplastic changes might be compromised by the squamous re-epithelialisation.

Adenocarcinoma↗