Biomedical subjects
Publications and source records attributed to P Layer.
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UNLABELLED: Most cystic lesions of the pancreas are pseudocysts caused by acute or chronic pancreatitis. Congenital cysts are rare and may occur in congenital syndromes like von Hippel-Lindau syndrome. Cystic tumors of the pancreas may be difficult to distinguish clinically; however, because of their malignant potential, in particular in cases of mucinous types, diagnostic verification is crucial. Hence, in all cases of cystic lesions of the pancreas, which are not a sequela of an etiological confirmed acute or chronic pancreatitis, a cystic neoplasm must be ruled out. Differential diagnosis may be difficult even with ultrasonography, computertomography, endoscopic retrograde cholangiopancreatography and serum analyses; endoscopic ultrasound, magnetic resonance tomography and analysis of the cyst content may be of particular value. The therapeutic approach for pseudocysts is now well established and guided by symptoms and complications. If a cystic neoplasm is suspected, surgical resection of the complete lesion is warranted. CONCLUSION: The most important differential diagnosis in all cystic lesions of the pancreas with atypical presentation includes a cystic neoplasm. Therefore complete resection is indicated whenever the suspicion cannot be ruled out.
In severe AP, infected necrosis is the leading cause of death. Prevention of pancreatic infection is the major goal in the treatment of patients with necrotizing pancreatitis. Adequate early antibiotic therapy seems to be promising in these patients. Their role and the optimal timing of the antibiotic therapy (e.g., benefit of prophylactic application) are discussed. Preliminary results of a study in patients with infected pancreatic necrosis and exclusively or primarily conservative treatment also are presented.
In summary, a prerequisite for the development of alcoholic pancreatitis would be the specific individual predisposition present in patients with late-onset idiopathic chronic pancreatitis. Furthermore, because the reported prevalence of chronic pancreatitis in patients with heavy alcohol consumption is markedly higher than the prevalence of late-onset idiopathic pancreatitis in the general population, the authors conclude that, in predisposed patients, alcohol consumption promotes the development of pancreatitis and accelerates the manifestation of symptoms and complications. This concept explains the observation that only a minority of severe alcoholics develop chronic pancreatitis. Conversely, in postmortem studies, a substantial proportion of older individuals without premortem evidence of pancreatic disease and no excessive alcohol history have pancreatic morphologic alterations resembling chronic pancreatitis. Thus, in the general population, a considerable number of asymptomatic "carriers," together with an undetected high prevalence of late-onset idiopathic chronic pancreatitis, may exist. In these persons, alcohol consumption might amplify and accelerate preexisting asymptomatic idiopathic pancreatic damage. As a consequence, in a dose-dependent manner, alcohol may lead to an earlier onset of or induce clinically apparent pancreatitis in persons who otherwise might never have had symptoms during their lives.
Severe pancreatic exocrine insufficiency leading to malabsorption of nutrients is one of the most important late features of chronic pancreatitis. In contrast to other key enzymes, pancreatic synthesis and secretion of lipase is impaired more rapidly, its intraluminal survival is shorter due to its higher susceptibility against acidic and proteolytic denaturation, and its luminal digestive action is hardly compensated by nonpancreatic mechanisms. As a consequence, steatorrhea is in general more severe and occurs several years before clinical malabsorption of protein or starch. Apart from the detrimental effects of nutrient deficiency, profound alterations of upper gastrointestinal secretory and motor functions may be an additional and hitherto underestimated consequence of increased nutrient delivery to distal intestinal sites. Effective reduction of nutrient malabsorption in pancreatic insufficiency requires delivery of sufficient enzymatic activity into the duodenal lumen simultaneously with meal nutrients. Modern enteric-coated pancreatin microsphere preparations attempt to achieve this by optimizing the size of individual microspheres and chemical properties of the coating. However, lipid digestion cannot be completely normalized in most patients by current standard therapy. In the future, acid and protease stable bacterial and fungal lipases with additional pH optima in the acidic milieu or animal or bioengineered human gastric lipase preparations may offer superior therapeutic alternatives. This review first summarizes current knowledge about secretion and luminal fate of pancreatic enzymes and their effects on nutrient digestion in health and chronic pancreatitis. Second, rationale, current standards, options, and future aspects of enzyme replacement therapy are discussed.
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With few exceptions, autoantibodies directed against the gene product of the tumor suppressor gene p53 are only detected in cancer patients. From 73 patients with various autoimmune diseases, we obtained 17 sera with elevated autoantibodies against the p53 protein comprising patients with SLE, Graves' disease, and immune vasculitis including Wegener's granulomatosis. The overall prevalence (23%) of p53 autoantibodies was comparable to that in various cancers; differences, however, were obvious with respect to the magnitude of antibody levels. Only 5% of seropositive colorectal cancer patients had levels within the critical range (150-180 U/ml) but nearly half (41%) of seropositive autoimmune disease patients were that low. None of the autoimmune disease patients exceeded 300 U/ml serum compared to more than 60% of seropositive colorectal cancer patients with higher levels. This remarkable difference in magnitude underlines the necessity of quantification of p53 autoantibodies over a mere qualitative determination. Patients with autoimmune diseases face an increased risk for malignancies. It still remains to be established whether p53 seropositivity in autoimmune diseases adds to the rare exceptions of p53AAb in non-malignant diseases or is indicative for a yet occult cancer.
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In most cases pain in the right upper abdominal quadrant is of biliary origin. Diseases of the biliary system are often visualized by ultrasonography; however, a negative test does not rule out a biliary cause. Moreover, a number of several non-biliary diseases have to be considered. Patient history, physical examination and laboratory findings determine the further diagnostic approach and include radiologic (i.e. CT/scintigraphy) and/or endoscopic (upper GI endoscopy, ERCP) examinations. In difficult diagnostic situations specialized diagnostic tools may be indicated (e.g. manometry in suspected dysfunction sphincter of the Oddi.
BACKGROUND: Sufficient intraluminal concentrations of 5-aminosalicylic acid (ASA) within inflamed regions of the intestine are required for therapeutic efficacy in inflammatory bowel disease. Various oral delayed release preparations have been developed to ensure that 5-ASA is set free in those parts of the gut, which are most frequently affected. However, resulting intraluminal concentrations within the small bowel are unknown. Therefore, we determined and compared 5-ASA release within different segments of the small bowel from an Eudragit L coated 5-ASA preparation (Salofalk) and from an ethylcellulose coated microsphere preparation (Pentasa). METHODS: Twelve healthy subjects were intubated with an oro-ileal multilumen-tube for marker perfusion, duodenal, jejunal and ileal aspiration of chyme and intestinal manometry. Each subject received 500 mg 5-ASA (Salofalk, n = 6, or Pentasa, n = 6) together with a semiliquid test meal. Intestinal aspirates, blood and urine samples were obtained in regular intervals for 7 to 10 hours and were analysed for 5-ASA and its main metabolite acetyl-5-ASA by HPLC. RESULTS: With Salofalk, gastric emptying of 5-ASA did not take place in the digestive, but in the subsequent interdigestive period. Luminal delivery of 5-ASA and acetyl-5-ASA increased from the duodenum (3% of dose) to the ileum (30% of dose). 10% of the dose administered were excreted in urine and about 90% reached the colon unreleased or solubilised. By contrast, with Pentasa, 5-ASA was delivered to the duodenum together with the test meal and released continuously throughout the small intestine (about 20% of dose solubilised at each intestinal site). Only 3.5% of the dose administered were excreted in urine. Deliver of 5-ASA to the colon was equal to Salofalk. CONCLUSIONS: From both preparations, considerable amounts of 5-ASA are released during small intestinal transit thus explaining therapeutic efficacy in small intestinal Crohn's disease. Because of specific release patterns, Salofalk may be of use especially in terminal ileal disease, where as patients with extensive small intestinal disease including the proximal small intestine might benefit from Pentasa.
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Amylase inhibition has gastrointestinal and metabolic effects that may aid in the treatment of diabetes and obesity. We tested whether 4 g of a commercially available wheat amylase inhibitor (WAI) affected postprandial carbohydrate (CHO) absorption and plasma glucose or hormones. Twelve persons (four lean and four obese nondiabetics and four obese type II diabetics) were studied on 2 separate days. After eating a weight maintenance diet (55% CHO, 20% protein, and 25% fat, as percentage of calories) for 3 days, subjects ate a breakfast containing 650 kcal, the same proportion of nutrients as calories, and in random order, either WAI or no WAI. Breath H2 and plasma glucose and hormones were measured every 15 and 30 min, respectively, for 7 h. WAI decreased the delta peak postprandial plasma glucose concentrations in 10 of 12 subjects (p < 0.05) and increased the breath H2 levels in 11 (p = 0.02); the increases in breath H2 were small, generally <20 ppm. No subject experienced a change in stools, diarrhea, or bloating. In response to WAI, gastric inhibitory peptide decreased (p < 0.05), peptide YY increased (p < 0.05), and there was a trend toward increased human pancreatic polypeptide (p = 0.07). Although WAI delays CHO absorption and reduces peak postprandial plasma glucose concentrations, overall CHO malabsorption is minimal (as reflected by breath hydrogen and hormones) and without symptoms. It, therefore, may be useful in treating type II diabetes mellitus.
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The etiology of acute pancreatitis is based on several causes, among which idiopathic nature (< 30%) is second to biliary stone disease (60-70%). It is still under debate whether alcohol as the main cause of chronic pancreatitic disease can cause acute pancreatitis. Based on Opie's "obstruction theory" of 1901 and experimental data, it is now widely accepted that the gallstone passage into or through the terminal biliopancreatic ductal system triggers acute (necrotizing) pancreatitis by causing pancreatic ductal obstruction. However, the sequential intracellular mechanisms in the pathogenesis of acute pancreatitis remain unclear. A co-localization hypothesis has been proposed to explain the premature intracellular activation of trypsinogen to trypsin: due to a yet unknown defect in the intracellular protein transport and sorting system within the acinar cell, lysosomal hydrolases (i.e. cathepsin B) and secretory proteins (i.e. trypsinogen) co-localize in a fragile postgolgi vacuole where activation can occur. In addition, alterations of exo- and endocytosis at the apical pole exist (i.e. secretion block). The pathophysiological events are characterized by local and systemic hypovolemia and (micro)circulatory failure aggravating necrosis, followed by ARDS, renal failure and several other severe complications (i.e. sepsis and DIC). The systemic overflow of proteolytic enzymes (i.e. PLA-2) and kinins plays a major role as mediating factor in severe cases, resulting in multiorgan failure.