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Query: UMLS:C0001339 (acute pancreatitis)
 10,593 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Progress in understanding pancreatic diseases has been limited by a number of factors. Primary problems include the absence of good animal models, and difficulty in understanding the origin of pancreatic disease since the disease is usually manifest by the progressive destruction of the gland itself. Beginning in 1995, our laboratory, with the support of the Midwest Multicenter Pancreatic Study Group, began investigating the genetic basis of hereditary pancreatitis. Utilization of information becoming available through the human genome project allowed us to map and identify the hereditary pancreatitis gene as cationic trypsinogen (PRSS1). Molecular modeling, and subsequent experimental evidence, has solved key elements of the mysteries surrounding the origin of acute pancreatitis and the progression of acute pancreatitis to chronic pancreatitis. The availability of new genetic information and genomic tools should produce a revolution in our understanding of pancreatic diseases.
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PMID:Hereditary pancreatitis: a model for understanding the genetic basis of acute and chronic pancreatitis. 1212 Feb 37

Hereditary pancreatitis is an autosomal dominant condition, which results in recurrent attacks of acute pancreatitis, progressing to chronic pancreatitis often at a young age. The majority of patients with hereditary pancreatitis express one of two mutations (R122H or N29I) in the cationic trypsinogen gene (PRSS1 gene). It has been hypothesised that one of these mutations, the R122H mutation causes pancreatitis by altering a trypsin recognition site so preventing deactivation of trypsin within the pancreas and prolonging its action, resulting in autodigestion. Families with these two mutations have been identified in many countries and there are also other rarer mutations, which have also been linked to hereditary pancreatitis. Patients with hereditary pancreatitis present in the same way as those with sporadic pancreatitis but at an earlier age. It is common for patients to remain undiagnosed for many years, particularly if they present with non-specific symptoms. Hereditary pancreatitis should always be considered in patients who present with recurrent pancreatitis with a family history of pancreatic disease. If patients with the 2 common mutations are compared, those with the R122H mutation are more likely to present at a younger age and are more likely to require surgical intervention than those with N29I. Hereditary pancreatitis carries a 40 % lifetime risk of pancreatic cancer with those patients aged between 50 to 70 being most at risk in whom screening tests may become important.
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PMID:Hereditary pancreatitis. 1250 40

The understanding of pathogenesis of acute and chronic pancreatitis has benefited from the progress made in genetic investigations. The discoveries of the gain of function mutations of cationic trypsinogen gene (PRSS1) and the loss of function mutations of pancreatic secretory trypsin inhibitor (SPINK 1) or other potential defects in genes that regulate pancreatic secretory function or modulate inflammatory response to pancreatic injury has changed our current concepts on the pathogenesis of pancreatitis. Genetic factors play an important role in the susceptibility to pancreatic injury, severity and evolution of inflammatory process, leading in some cases to chronic inflammation and/or fibrosis. Acute pancreatitis is viewed as an event and chronic pancreatitis as a process, sequentially linked, reflecting a complex interaction between genetic and environmental factors.
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PMID:Genetic factors in pancreatitis. 1580 Jun 94

Hereditary pancreatitis is an autosomal dominant disease with incomplete penetrance (80%), accounting for approximately 1% of all cases of pancreatitis. It is characterized by the onset of recurrent attacks of acute pancreatitis in childhood and frequent progression to chronic pancreatitis. Whitcomb et al. identified the cationic trypsinogen gene (PRSS1) on chromosome 7q35 as the site of the mutation that causes hereditary pancreatitis. The European registry of hereditary pancreatitis and familial pancreatic cancer (EUROPAC) aims to identify and make provisions for those affected by hereditary pancreatitis and familial pancreatic cancer. The most common mutations in hereditary pancreatitis are R122H, N29I and A16V but many families have been described with clinically defined hereditary pancreatitis where there is no PRSS1 mutation. It is known that the cumulative lifetime risk (to age 70 years) of pancreatic cancer is 40% in individuals with hereditary pancreatitis. This subset of individuals form an ideal group for the development of a screening programme aimed at detecting pancreatic cancer at an early stage in an attempt to improve the presently poor long-term survival. Current screening strategies involve multimodality imaging (computed tomography, endoluminal ultrasound) and endoscopic retrograde cholangiopancreatography for pancreatic juice collection followed by molecular analysis of the DNA extracted from the juice. The potential benefit of screening (curative resection) must be balanced against the associated morbidity and mortality of surgery. Philosophically, the individual's best interest must be sought in light of the latest advances in medicine and science following discussions with a multidisciplinary team in specialist pancreatic centres.
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PMID:Hereditary pancreatitis and secondary screening for early pancreatic cancer. 1635 43

The chylomicronemia syndrome is well recognized as a rare etiologic factor of acute pancreatitis; however, whether hypertriglyceridemia can cause chronic pancreatitis (CP) remains unclear. We describe the long-time course of 2 brothers with the familial chylomicronemia syndrome caused by identical compound heterozygous mutations in the lipoprotein lipase (LPL) gene with markedly reduced LPL activity. Other etiologic factors were excluded, including mutations in the PRSS1, SPINK1, and CFTR gene. Although both brothers had recurrent acute pancreatitis and the same LPL genotype, CP became evident in only one patient. Progression to CP was associated with a more severe disease course. Thus, the chylomicronemia syndrome may cause CP in the absence of other known causative factors, and similar to alcoholic and hereditary CP, a more severe disease course is associated with disease progression.
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PMID:Recurrent acute and chronic pancreatitis in two brothers with familial chylomicronemia syndrome. 1655 44

Chronic pancreatitis (CP) is characterised by pancreatic inflammation and fibrosis leading eventually to destruction of pancreatic parenchyma and loss of exocrine and endocrine function. A model of interactions between environmental triggers of pancreatic inflammation and disease susceptibility or modifying genes (including PRSS1, SPINK1 and CFTR) provides a framework within which to understand disease pathogenesis. Early in the disease, when fibrosis is mild and pancreatic damage limited, it is difficult to distinguish CP from recurrent acute pancreatitis (RAP) although it is likely these represent opposite ends of a spectrum of disease with a common aetiology in which CP represents either a later disease stage or disease in individuals predisposed to generate a chronic fibrogenic inflammatory response. Pain is a dominant feature resulting in part from neuroimmune interactions within the pancreas. Diagnosis at an early stage of disease is challenging, though in later stages is dependent upon the demonstration of pancreatic fibrosis and duct ectasia using one or more imaging modalities including transabdominal and endoscopic ultrasound, CT and MRCP or ERCP. Current treatments are largely supportive and reactive. The challenge for pediatricians is to achieve diagnosis at an early stage of the disease and to develop treatments that can alter its natural history.
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PMID:Chronic pancreatitis. 1709 Sep 3

Hereditary pancreatitis is a rare, autosomal dominant, inherited disease characterized by recurrent attacks of acute pancreatitis with the development of chronic pancreatitis and an increased risk of pancreatic cancer. R122H or N29I mutation in cationic trypsinogen (protease serine 1, PRSS1) gene causes hereditary pancreatitis. R122H mutation is the most common mutation that causes pancreatitis by preventing deactivation of trypsin within the pancreas and prolonging its action. Three members of the family, the patient, her elder son, and her niece experienced recurrent attacks of pancreatitis. We analyzed five exons of the PRSS1 gene in DNA samples of five family members including her husband and younger son who were asymptomatic. We found out that four members of the family, the patient, her two sons, and her niece, had R122H mutation in the exon 3 of PRSS1 gene. Finally, we diagnosed hereditary pancreatitis in two households in the same family.
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PMID:[Three cases of hereditary pancreatitis in two households in the same family associated with R122H mutation in cationic trypsinogen gene]. 1764 59

Acute pancreatitis and chronic pancreatitis are complex inflammatory disorders of the pancreas with unpredictable severity, complications, and clinical courses. Growing evidence for genetic risk and modifying factors, plus strong evidence that only a minority of patients with these disorders are heavy alcohol drinkers, has revolutionized our concept of these diseases. Once considered a self-inflicted injury, pancreatitis is now recognized as a complex inflammatory condition like inflammatory bowel disease. Genetic linkage and candidate gene studies have identified six pancreas-targeting factors that are associated with changes in susceptibility to acute and/or chronic pancreatitis, including cationic trypsinogen (PRSS1), anionic trypsinogen (PRSS2), serine protease inhibitor Kazal 1 (SPINK1), cystic fibrosis transmembrane conductance regulator (CFTR), chymotrypsinogen C (CTRC) and calcium-sensing receptor (CASR). Patients with mutations in these genes are at increased risk of pancreatitis caused by a variety of stresses including hyperlipidemia and hypercalcemia. Multiple studies are reporting new polymorphisms, as well as complex gene x gene and gene x environmental interactions.
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PMID:Genetic aspects of pancreatitis. 2005 46

The association of alcohol consumption and acute pancreatitis (AP) has been well documented. Extensive research in the field of alcohol-induced AP has allowed scientists to understand the different aspects by which ethanol may alter pancreatic cellular function. However, despite the recognition and understanding of these proposed mechanisms, the basic question that remains unanswered is that although alcohol is consumed the world over, why is it that only some people develop AP? Epidemiologic data indicates a higher frequency of alcohol-induced AP in geographical locations where surrogate/home-brewed alcoholic beverages are freely available. These surrogate/home-brewed alcoholic beverages contain in addition to ethanol, higher alcohols (e.g. propanol and butanol) and other by-products/contaminants (e.g. acids, aldehydes and esters), the potential of which to induce pancreatic damage has been incompletely studied. Mutations in genes that metabolise alcohol as well as those that protect the acinar cells and the extra-acinar milieu from prematurely activated digestive enzymes (e.g. genetic mutations in SPINK1 or PRSS1 genes) have also been noted in these geographical locations. Based on the available epidemiologic, clinical and basic research data available at the present time, we propose a unifying hypothesis presenting for the first time the 'critical mass' concept. We hypothesise that it is the achievement of a 'critical mass' of damaged acinar cells that is required to trigger off the inflammatory cascade leading to a clinically recognised attack of AP. The consequence of a critical mass of damaged acinar cells is the generation of sufficient mediators to result in clinical AP. While the consumption of alcohol does damage acinar cells, the number of damaged acinar cells does not necessarily reach the 'critical mass' with every binge. Co-factors such a high fat or protein meals are required to sensitize the acinar cells by raising the metabolic state to a high level which compromises the viability of the cells. In addition, the existence of genetic mutations and / or the consumption of surrogate alcoholic beverages, by facilitating acinar cell damage, directly or indirectly, potentially hasten the achievement of the 'critical mass', leading to an attack of AP.
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PMID:Alcohol-induced acute pancreatitis: the 'critical mass' concept. 2018 33

The paper presents the data available in the literature on mutations in known genes in pancreatitis, such as cationic trypsinogen (PRSS1), pancreatic secretory trypsin inhibitor (PSTI/SPINK1), cystic fibrosis (CFTR), and apolipoprotein E (APOE) genes, as well as the new candidate gene--chymotrypsinogen (CTRC). It also gives the results of the authors studies estimating the spread of the mutations in the PRSS1 (2.5%), PSTI/SPINK1 (3.3%), and CFTR (0.8%) genes, as well as APOE polymorphism in patients with pancreatitis. It is shown that the E4 allele of the APOE gene was more frequently identified in patients with acute pancreatitis than in those with chronic pancreatitis (0.143 +/- 0.05 and 0.026 +/- 0.02, respectively; p < 0.05). An overview is given of 7 major classes of candidate genes implicated in the pathogenesis of cholesterol cholelithiasis (CL): hepatic enzymes regulating blood lipid composition; receptors of lipoproteins, hepatic and intestinal membrane and intracellular transport proteins; factors regulating the transcription of lipids and bile salts, cholecystokinin and its receptors, and mucin. In the authors' epidemiological study, the spread of APOE alleles and genotypes did not differ in women with and without CL; low molecular-weight apolipoprotein(a) isoforms (B, S2) were significantly found in patients with CL than in those without CL; the spread of the CG genotype in the TRPM8 gene was significantly lower in women with cholesterol CL than that in the Novosibirsk population. These polymorphisms have been proved to be associated with bile cholesterol concentrations in women with cholesterol CL. The opposite effect of the APOE4 allele on gallbladder stone formation processes is demonstrated, by using the APOE polymorphism as an example, which shows it necessary to examine each specific population to elicit a possible association between the polymorphism of different genes and gastrointestinal tract diseases.
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PMID:[Genetic aspects of digestive diseases. Part 1]. 2038 81


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