Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1389183 (autodigestion)
 317 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic pancreatitis is considered a progressive damage of the anatomic structure of the pancreas. Alcoholism and diseases of the bile tract are to be considered in the first place among the many etiologic factors. The pathogenetic principle is an intrapancreatic activation of enzymes combined with autodigestion. The leading symptome is abdominal pain. Besides laboratory tests and X-ray examination the main methods of diagnosis are the examination of endocrine and exocrine function of the pancreas, endoscopic-radiological cholangio-pancreaticography (ERCP) and sonography. More than half the patients with chronic pancreatitis can be treated satisfactory by a diet poor in fat, the abstinence of alcohol and the substitution of enzymes.
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PMID:[Chronic pancreatitis]. 122 4

The pathophysiology of pancreatic autodigestion is poorly understood. Pancreatitis affects all age groups, and the diagnosis is sometimes missed when serum amylase and lipase activities are not measured in the child with abdominal pain. Acute pancreatitis in children has become a more commonly seen condition and the causes have varied. Laboratory and radiological studies play an important role in determining the diagnosis and prognosis. Family history is important in the diagnosis of idiopathic hereditary pancreatitis. Most acute episodes resolve with supportive care, but the mortality in acute pancreatitis is currently about 15% (Hadorn et al., 1980). Endoscopic retrograde cholangiopancreatography or an endoscopic retrograde pancreatogram may be necessary to investigate relapses of pancreatitis. Chronic pancreatitis can be a life-threatening condition requiring lifetime medical management.
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PMID:Pancreatitis in children. 147 58

Hemorrhage from pseudocyst may be the most serious complication of chronic pancreatitis: the mortality from such hemorrhage approaches 80%. The bleeding arises from a major artery--the artery is eroded by the basic process of autodigestion, and the pseudocyst is converted into a pseudoaneurysm. The wall of the pseudoaneurysm is subjected to arterial pressure and may perforate into the peritoneal cavity, an adjacent segment of the gastrointestinal tract, or the pancreatic ductal system. Clinical signs and indications of complicated pseudocyst are sudden abdominal pain, hypotension, sudden increase in abdominal tenderness, decrease of hematocrit and sudden disappearance of the mass. Sonography, CT and angiography accurately define the bleeding lesion and greatly aid in planning operative strategy. Surgery, angiographic embolisation, or a combination of both may be employed. Transcystic arterial ligation and internal drainage of the pseudocyst or distal pancreatectomy are the operative procedures of choice and give the best results.
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PMID:[Hemorrhage-induced rupture of the pancreatic pseudocyst]. 159 28

The association between histopathological changes and the incidence of abdominal pain in patients with chronic pancreatitis was reviewed from published reports, and compared with that in our own series (n = 65). Recurrent tissue necrosis caused by autodigestion, and the formation of pseudocysts, are the likely causes of the intermittent pain that marks the early stages of chronic pancreatitis. In contrast, the persistent pain of advanced chronic pancreatitis is associated with incomplete duct obstruction in a pancreas that is still able to secrete. The cause of persistent pain may therefore be segmental distension of the walls of the duct as a result of focally increased pressure. Perineural scarring has been seen in both painful and painless chronic pancreatitis.
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PMID:Pathology of chronic pancreatitis and pancreatic pain. 234 44

Acute pancreatitis may follow a mild or a severe course. Whereas mild or edematous pancreatitis is a self-limiting disease with a low complication rate and low death rate, morbidity and mortality in severe or necrotizing pancreatitis are still unacceptably high. The major problem is the lack of a specific drug, especially in the early phase of the disease, to interfere with the systemic inflammatory response syndrome and to limit or prevent complications of the disease. Although the initiating pathophysiological process is not known, the destruction of the gland ('autodigestion') by digestive enzymes may be responsible for disease progression. Inhibition of pancreatic activity, which reduces exocrine secretion and further prevents the release and activation of enzymes, was therefore suggested as a specific treatment concept. The results of clinical investigations using somatostatin or its analogue are controversial, since all these trials had low statistical power. In a recent multicenter randomized controlled study with a large number of patients (n = 302) (and an adequate level of disease severity), no benefit of octreotide on progression or outcome was found. Chronic pancreatitis is characterized by an irreversible destruction of the exocrine and endocrine pancreatic parenchyma leading to maldigestion and diabetes. Pain, which may be caused by increased ductal pressure, is one of the most dominant symptoms in chronic pancreatitis. However, no beneficial effects on pain with pancreatic exocrine secretion-inhibiting drugs have been demonstrated. Treatment of other complications of the disease (pseudocyst formation, fistula and pancreatic ascites), with somatostatin or octreotide has given conflicting results. However, in a prophylactic clinical setting (e.g. elective pancreatic surgery) the inhibition of exocrine pancreatic secretion reduces complications.
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PMID:The role of octreotide and somatostatin in acute and chronic pancreatitis. 1020 28

Alcohol consumption is the most important etiological factor of chronic pancreatitis (around 70%). Smoking, ethnic-racial predispositions, diets high and low in fat and high in protein may also contribute to the development of chronic pancreatitis. Non-alcoholic chronic pancreatitis of unknown cause makes up 10% to 30% of patients with chronic pancreatitis. Two subgroups have been reported: juvenile (about 25 years) and senile (up 65 years). Tropical pancreatitis has been observed in children and young men in many African and Asian countries. This disease develops because of fat and protein deficiency or nutritional deficiency in general, also due to cyanogenes present in cassava. Hereditary chronic pancreatitis is a rare disease connected with autosomal transmissions. Dr Whitcomb reported, that hereditary chronic pancreatitis developed because of trypsines mutation. Mutant "hypertrypsin" is not inactivated by enzymes; this way it leads to pancreas autodigestion. Obstructive chronic pancreatitis is caused by longterm pancreatic ducts obstruction. In many rare causes leading to chronic pancreatitis among other are: hypercalcaemia, hyperlipoproteinemia, some drugs and pancreatitis associated with autoimmune disorders. Newest information about etiology and pathogenesis of chronic pancreatitis is yielded by recent immunohistochemical research. This research shows increasing irregular improper antigens expression of class I and/or class II MHC in pancreas as well as the role of Transforming Growth Factor Alpha in chronic pancreatitis development. This illness is still a puzzling problem.
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PMID:[Contemporary opinions on the etiology of chronic pancreatitis]. 1050 45

Chronic pancreatitis (CP) is a continuing or relapsing inflammatory disease of the pancreas. In approximately one-third of all cases, no aetiological factor can be found, and these patients are classified as having idiopathic disease. Pathophysiologically, autodigestion and inflammation may be caused by either increased proteolytic activity or decreased protease inhibition. Several studies have demonstrated mutations in the cationic trypsinogen gene (PRSS1) in patients with hereditary or idiopathic CP. It is thought that these mutations result in increased trypsin activity within the pancreatic parenchyma. Most patients with idiopathic or hereditary CP, however, do not have mutations in PRSS1 (ref. 4). Here we analysed 96 unrelated children and adolescents with CP for mutations in the gene encoding the serine protease inhibitor, Kazal type 1 (SPINK1), a pancreatic trypsin inhibitor. We found mutations in 23% of the patients. In 18 patients, 6 of whom were homozygous, we detected a missense mutation of codon 34 (N34S). We also found four other sequence variants. Our results indicate that mutations in SPINK1 are associated with chronic pancreatitis.
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PMID:Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis. 1083 40

Hereditary pancreatitis is an unusual form of acute and chronic pancreatitis with a familial predisposition. Recently, the gene mutations causing most cases of hereditary pancreatitis have been identified in the cationic trypsinogen gene. The known mutations are trypsinogen R117H and N211. These may predispose to acute pancreatitis by eliminating one of the fail-safe mechanisms used by the pancreas to eliminate prematurely activated trypsin. Accumulation of active trypsin mutants are hypothesized to initiate a digestive enzyme activation cascade in the pancreatic acinar cells leading to autodigestion, an intense inflammatory response, and acute pancreatitis. The observation that these patients also develop typical chronic pancreatitis and may later develop pancreatic cancer provides strong evidence that these conditions are linked. Knowledge of the pathophysiological conditions leading to acute and chronic pancreatitis and the development of a transgenic mouse expressing the mutant human trypsinogen genes will provide directions and tools necessary for the effective treatment or prevention of this human disease.
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PMID:Hereditary pancreatitis: new insights, new directions. 1103 Jun 5

Hereditary pancreatitis is due to heterozygosity for gain-of-function mutations in the cationic trypsinogen gene which result in increased levels of active trypsin within pancreatic acinar cells and autodigestion of the pancreas. The number of disease-causing defects is generally considered to be low. To gain further insight into the molecular basis of this disorder, DNA sequence analysis of all five exons was performed in 109 unrelated patients with idiopathic chronic pancreatitis in order to determine the variability of the underlying mutations. Two German females and one German male were carriers of the most common N29I and R122H mutations (trypsinogen numbering system). In a Turkish proband, an arginine (CGT) to cysteine (TGT) substitution at amino acid position 116 was identified. Family screening demonstrated that the patient had inherited the mutation from his asymptomatic father and that he had transmitted it to both of his children, his daughter being symptomatic since the age of 3 years. In addition, a German male was found to be a heterozygote for a D100H (GAC-->CAC) amino acid replacement. Our data provide evidence for genetic heterogeneity of hereditary pancreatitis. The growing number of cationic trypsinogen mutations is expected to change current mutation screening practices for this disease.
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PMID:R116C mutation of cationic trypsinogen in a Turkish family with recurrent pancreatitis illustrates genetic microheterogeneity of hereditary pancreatitis. 1184 79

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


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