Microlithiasis of the gallbladder: role of endoscopic ultrasonography in patients with idiopathic acute pancreatitis

OBJECTIVES: Causes may be found in most cases of acute pancreatitis, however no etiology is found by clinical, biological and imaging investigations in 30% of these cases. Our objective was to evaluate results from endoscopic ultrasonography (EUS) for diagnosis of gallbladder microlithiasis in patients with unexplained (idiopathic) acute pancreatitis. METHODS: Thirty-six consecutive non-alcoholic patients with diagnoses of acute pancreatitis were studied over a five-year period. None of them showed signs of gallstones on transabdominal ultrasound or tomography. We performed EUS within one week of diagnosing acute pancreatitis. Diagnosis of gallbladder microlithiasis on EUS was based upon findings of hyperechoic signals of 0.5-3.0 mm, with or without acoustic shadowing. All patients (36 cases) underwent cholecystectomy, in accordance with indication from the attending physician or based upon EUS diagnosis. RESULTS: Twenty-seven patients (75%) had microlithiasis confirmed by histology and nine did not (25%). EUS findings were positive in twenty-five. Two patients had acute cholecystitis diagnosed at EUS that was confirmed by surgical and histological findings. In two patients, EUS showed cholesterolosis and pathological analysis disclosed stones not detected by EUS. EUS diagnosed microlithiasis in four cases not confirmed by surgical treatment. In our study, sensitivity, specificity and positive and negative predictive values to identify gallbladder microlithiasis (with 95% confidence interval) were 92.6% (74.2-98.7%), 55.6% (22.7-84.7%), 86.2% (67.4-95.5%) and 71.4% (30.3-94.9%), respectively. Overall EUS accuracy was 83.2%. CONCLUSIONS: EUS is a very reliable procedure to diagnose gallbladder microlithiasis and should be used for the management of patients with unexplained acute pancreatitis. This procedure should be part of advanced endoscopic evaluation.

Immunology of Dermatophytosis

The immune response to infection by dermatophytes ranges from a non-specific host mechanism to a humoral and cell-mediated immune response. The currently accepted view is that a cell-mediated immune response is responsible for the control of dermatophytosis. Indeed, some individuals develop a chronic or recurrent infection mediated by the suppression of a cell-mediated immune response. The immune response to Trichophyton is unusual in that this fungus can elicit both immediate hypersensitivity (IH) and delayed-type hypersensitivity (DTH) in different individuals when they are submitted to a skin test reaction. Understanding the nature and function of the immune response to dermatophytes is an exciting challenge that might lead to novel approaches in the treatment and immunological prophylaxis of dermatophytosis.

Immunology of multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) leading to demyelination, axonal damage, and progressive neurologic disability. The development of MS is influenced by environmental factors, particularly the Epstein-Barr virus (EBV), and genetic factors, which include specific HLA types, particularly DRB1*1501-DQA1*0102-DQB1*0602, and a predisposition to autoimmunity in general. MS patients have increased circulating T-cell and antibody reactivity to myelin proteins and gangliosides. It is proposed that the role of EBV is to infect autoreactive B cells that then seed the CNS and promote the survival of autoreactive T cells there. It is also proposed that the clinical attacks of relapsing-remitting MS are orchestrated by myelin-reactive T cells entering the white matter of the CNS from the blood, and that the progressive disability in primary and secondary progressive MS is caused by the action of autoantibodies produced in the CNS by ­meningeal lymphoid follicles with germinal centers.

Molecular immunology databases and data repositories

Over recent years databases have become an extremely important resource for biomedical research. Immunology research is increasingly dependent on access to extensive biological databases to extract existing information, plan experiments, and analyse experimental results. This review describes 15 immunological databases that have appeared over the last 30 years. In addition, important issues regarding database design and the potential for misuse of information contained within these databases are discussed. Access pointers are provided for the major immunological databases and also for a number of other immunological resources accessible over the World Wide Web (WWW). (C) 2000 Elsevier Science B.V. All rights reserved.

Computational immunology: The coming of age

The explosive growth in biotechnology combined with major advancesin information technology has the potential to radically transformimmunology in the postgenomics era. Not only do we now have readyaccess to vast quantities of existing data, but new data with relevanceto immunology are being accumulated at an exponential rate. Resourcesfor computational immunology include biological databases and methodsfor data extraction, comparison, analysis and interpretation. Publiclyaccessible biological databases of relevance to immunologists numberin the hundreds and are growing daily. The ability to efficientlyextract and analyse information from these databases is vital forefficient immunology research. Most importantly, a new generationof computational immunology tools enables modelling of peptide transportby the transporter associated with antigen processing (TAP), modellingof antibody binding sites, identification of allergenic motifs andmodelling of T-cell receptor serial triggering.

Acute Pancreatitis Hypertonic Saline Increases Heat Shock Proteins 70 and 90 and Reduces Neutrophil Infiltration in Lung Injury

Objectives: Acute pancreatitis (AP) protease release induces lung parenchymal destruction via matrix metalloproteinases (MMPs), a neutrophil (polymorphonuclear leukocyte)-dependent process. Recent studies in hemorrhagic shock revealed that hypertonic saline (HTS) has an anti-inflammatory effect and can inhibit a variety of neutrophil functions. The aim of this study was to determine whether HTS and its actions in the pathway of neutrophil migration, MMPs, and heat shock proteins (HSPs) are effective in protecting the lung from injury associated with AP. Methods: We determined neutrophil infiltration and expressions of MMPs and HSPs in the lung tissue after AP induced by retrograde infusion of 2.5% of sodium taurocholate. Results: Animals submitted to AP that received HTS compared with those who received normal saline presented with increased HSP70 and HSP90 expressions and reduced myeloperoxidase levels and MMP-9 expression and activity. Conclusions: Our data raised the hypothesis that a sequence of HTS lung protection events increases HSP70 and HSP90, inhibiting infiltration of neutrophils and their protease actions in the lung.

Hypertonic saline reduces metalloproteinase expression in liver during pancreatitis

P>We recently demonstrated that hypertonic saline reduces inflammation and mortality in acute pancreatitis. The present study investigated the effects of hypertonic saline in metalloproteinase (MMP) regulation and pancreatitis-associated hepatic injury. Wistar rats were divided into four groups: (i) control, not subjected to insult or treatment; (ii) no treatment (NT), induction of pancreatitis (retrograde infusion of 2.5% sodium taurocholate (1.0 mL/kg)), but no further treatment; (iii) normal saline (NS), induction of pancreatitis and treatment with normal saline (0.9% NaCl, 34 mL/kg, i.v. bolus, 1 h after the induction of pancreatitis); and (iv) hypertonic saline (HS), induction of pancreatitis and treatment with hypertonic saline (7.5% NaCl, 4 mL/kg administered over a period of 5 min, 1 h after the induction of pancreatitis). In all four groups, 4, 12 and 24 h after the induction of pancreatitis, liver tissue samples were assayed to determine levels of MMP-2, MMP-9, 47 kDa heat shock protein (HSP47) and collagen (Type I and III). Compared with the control group, MMP-9 expression and activity was increased twofold in the NS and NT groups 4 and 12 h after the induction of pancreatitis, but remained at basal levels in the HS group. In contrast, MMP-2 expression was increased twofold 12 h after the induction of pancreatitis only in the NS group, whereas the expression of HSP47 was increased 4 h after the induction of pancreatitis in the NS and NT groups. Greater extracellular matrix remodelling occurred in the NS and NT groups compared with the HS group, probably as a result of the hepatic wound-healing response to repeated injury. However, the collagen content in hepatic tissue remained at basal levels in the HS group. In conclusion, the results of the present study indicate that hypertonic saline is hepatoprotective and reduces hepatic remodelling, maintaining the integrity of the hepatic extracellular matrix during pancreatitis. Hypertonic saline-mediated regulation of MMP expression may have clinical relevance in pancreatitis-associated liver injury.

A Comparison of the Consensus and Clinical Definitions of Pancreatitis With a Proposal to Redefine Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis

Objectives: We evaluated the correlation between the consensus and clinical definitions of pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP), with the objective of updating and revising the definition of post-ERCP pancreatitis (PEP). Methods: Three hundred patients were subjected to serial serum amylase & lipase levels testing and abdominal computed tomography scan for abdominal pain after ERCP. Main outcome measures included the correlation between consensus and clinical definitions. Results: Using consensus criteria, 25 patients had acute pancreatitis (11 of mild and 14 of moderate severity). Forty-three patients had acute pancreatitis using the clinical definitions (18 of mild and 25 of moderate severity). At 4 hours, serum hyperamylasemia of under 1.5-fold and at 12 hours a serum hyperamylasemia of under 2-fold had a negative predictive value of 0.94 for development of PEP. Serum hyperamylasemia following ERCP had a poor positive predictive value for PEP. Conclusions: Clinical and consensus definitions are poorly correlated; use of the latter leads to significant underrecognition of PEP. The adoption of clinical definition results in uniformity of diagnosis of pancreatitis for clinical care and research. Serum amylase levels at 4 and 12 hours after ERCP have a high negative predictive value for PEP.

CFTR Polymorphisms in Patients with Alcoholic Chronic Pancreatitis

Introduction: Pancreas susceptibility to alcohol is variable and only 5-10% of chronic alcohol abusers develop chronic pancreatitis; the role of genetic factors in this process is unknown. The CFTR gene encodes a protein that acts on epithelial cells and plays a key role in normal exocrine pancreatic function. Methods: This study investigated the frequency of polymorphisms in intron 8 of the CFTR gene in patients with alcoholic chronic pancreatitis. Three groups of patients were studied: group A-68 adult alcoholics with a diagnosis of chronic pancreatitis; group B-68 adult alcoholics without pancreatic disease or liver cirrhosis and group C-104 healthy nonalcoholic adults. Results: T5/T7 genotype was more frequent in group A (11.8%) than in group B (2.9%) (p = 0.0481), and there was no statistical difference when groups A and C (5.8%) were compared (p = 0.1317). The haplotype combination (TG) 10-T7/(TG) 11-T7 was more frequent in groups B (23.5%) and C (20.2%) than in group A (7.3%) (p = 0.0080 and 0.0162). Conclusion: There are differences when these three groups are compared and individuals with T5/T7 genotype might have a greater risk of developing chronic pancreatitis when they become chronic alcoholics. Copyright (C) 2008 S. Karger AG, Basel and IAP

Acute pancreatitis in juvenile systemic lupus erythematosus: a manifestation of macrophage activation syndrome?

Acute pancreatitis (AP) is a rare and life-threatening manifestation of juvenile systemic lupus erythematosus (JSLE). The objective of this study was to evaluate the prevalence and clinical features of AP in our JSLE population. AP was defined according to the presence of abdominal pain or vomiting associated to an increase of pancreatic enzymes and/or pancreatic radiological abnormalities. Of note, in the last 26 years, 5367 patients were followed up at our Pediatric Rheumatology Unit and 263 (4.9%) of them had JSLE diagnosis (ACR criteria). AP was observed in 4.2% (11/263) of JSLE patients. The median of age of the JSLE patients at AP diagnosis was 12.4 years (8.8-17.9). All of them had lupus disease activity at AP onset. Three patients were receiving corticosteroids before AP diagnosis. Interestingly, 10/11 JSLE patients fulfilled preliminary guidelines for macrophage activation syndrome, three of them with macrophage hemophagocytosis in bone marrow aspirate and hyperferritinemia. The hallmark of this syndrome is excessive activation and proliferation of T lymphocytes and macrophages with massive hypersecretion of proinflammatory cytokines and clinically it is characterized by the occurrence of unexplained fever, cytopenia and hyperferritinemia. AP treatment was mainly based on intravenous methylprednisolone. Four JSLE patients with AP died and two developed diabetes mellitus. In conclusion, AP was a rare and severe manifestation in active pediatric lupus. The association between AP and macrophage activation syndrome suggests that the pancreas could be a target organ of this syndrome and that pancreatic enzyme evaluation should also be carried out in all patients. Lupus (2010) 19, 1654 1658.

Anti-Inflammatory Effects of Peritoneal Lavage in Acute Pancreatitis

Objectives: Intraperitoneal administration of trypsin stimulates the production of cytokines from peritoneal macrophages. Removing the pancreatitis-associated ascitic fluid from the peritoneal cavity may decrease the systemic inflammatory response in acute pancreatitis (AP). We investigated the effect of peritoneal lavage on the systemic inflammatory response in severe AP. Methods: Acute pancreatitis was induced in Wistar rats by 5% taurocholate intraductal injection. Peritoneal lavage was performed for 4 hours after onset of AP. At 4 hours after induction of AP, serum samples were assayed for amylase and inflammatory cytokines (tumor necrosis factor alpha, interleukin-6 [IL-6], and IL-10). Expression of pancreatic cyclooxygenase-2 and inducible nitric oxide synthase, liver mitochondrial function, and pulmonary myeloperoxidase activities were determined. Results: Peritoneal lavage after AP led to a decrease in serum levels of tumor necrosis factor alpha and IL-6 and an increase in IL-10. In the pancreas, this treatment reduced cyclooxygenase-2 and inducible nitric oxide synthase expression. Liver mitochondrial dysfunction was also reduced. There were no differences on serum amylase levels and pulmonary myeloperoxidase between groups with AP. Conclusions: Peritoneal lavage has a systemic anti-inflammatory effect in severe AP and may be able to decrease the severity of severe AP.

CO(2) Abdominal Insufflation Decreases Local and Systemic Inflammatory Response in Experimental Acute Pancreatitis

Objectives: Acute pancreatitis (AP) is a serious disease that is amplified by an associated systemic inflammatory response. We investigated the effect of CO(2) pneumoperitoneum on the local and systemic inflammatory response in AP. Methods: Acute pancreatitis was induced in Wistar rats by 5% taurocholate intraductal injection. Carbon dioxide pneumoperitoneum was applied for 30 minutes before the induction of AP. Inflammatory parameters were evaluated in the peritoneum (ascites, cell number, and tumor necrosis factor alpha [TNF-alpha]), serum (amylase, TNF-alpha, interleukin-6 [IL-6], and IL-10), pancreas (myeloperoxidase [MPO] activity, cyclooxygenase 2 and inducible nitric oxide synthase expression, and histological diagnosis), liver, and lung (mitochondria dysfunction and MPO activity). Results: Abdominal insufflation with CO(2) before induction of AP caused a significant decrease in ascites volume, cells, and TNF-alpha in the peritoneal cavity and in serum TNF-alpha and IL-6 but not IL-10 levels. In the pancreas, this treatment reduced MPO activity, acinar and fat necrosis, and the expression of inducible nitric oxide synthase and cyclooxygenase 2. There were no significant differences on serum amylase levels, liver mitochondrial function, and pulmonary MPO between groups. Conclusions: Our data demonstrated that CO(2) pneumoperitoneum reduced pancreatic inflammation and attenuated systemic inflammatory response in AP. This article suggests that CO(2) pneumoperitoneum plays a critical role on the better outcome in patients undergoing laparoscopic pancreatic surgery.

Do the Effects of Pentoxifylline on the Inflammatory Process and Pancreatic Infection Justify Its Use in Acute Pancreatitis?

Severe acute pancreatitis is associated with high morbidity and mortality rates. At the present time, no specific therapy has been shown to be uniformly effective in reducing morbidity and mortality in this disease. The aim of this study was to determine the effects of pentoxifylline on the pancreatic and systemic inflammatory process, pancreatic infection, and mortality rate in severe acute pancreatitis in rats. Methods: One hundred and twenty male Wistar rats were divided into 3 groups: sham, pancreatitis, and pentoxifylline (acute pancreatitis induction plus administration of 25 mg/kg pentoxifylline). Inflammatory response was measured by histological studies, inflammatory cytokine production (IL-6, IL-10, and TNF-alpha), and mortality rate. Pancreatic infection was evaluated by bacterial cultures expressed in colony-forming units per gram. Results: Pentoxifylline-treated animals had a statistically significant reduction of inflammatory cytokine levels, pancreatic histological damage, occurrence of bacterial translocation and pancreatic infection (p < 0.05), associated with a significant reduction in mortality rate. Conclusions: Pentoxifylline administration in this experimental model of acute pancreatitis reduces local and systemic inflammatory responses and decreases the pancreatic infection and the mortality rate. Copyright (C) 2009 S. Karger AG, Basel and IAP