Acute pancreatitis is characterized by the pathologic activation of zymogens within pancreatic acinar cells. The process requires a rise in cytosolic Ca 2؉ from undefined intracellular stores. We hypothesized that zymogen activation is mediated by ryanodine receptor (RYR)-regulated Ca 2؉ release, because early zymogen activation takes place in a supranuclear compartment that overlaps in distribution with the RYR. Ca 2؉ signals in the basolateral, but not apical, region of acinar cells observed during supraphysiologic agonist stimulation were dependent on RYR Ca 2؉ release. Inhibition of RYR or depletion of RYR-sensitive Ca 2؉ pools each reduced pathologic zymogen activation in isolated acinar cells, but neither treatment affected amylase secretion. Inhibition of RYR also inhibited zymogen activation in vivo. We propose that Ca 2؉ release from the RYR mediates zymogen activation but not enzyme secretion. The findings imply a role for the RYR in acute pancreatitis.pancreatic acinar cell ͉ dantrolene ͉ calcium signaling
Background: Preliminary data show that endosonography guided fine needle aspiration (EUS-FNA) may be an accurate method for diagnosing sarcoidosis. However, these data were obtained in a small selected group of patients with a very high pretest probability of sarcoidosis. This retrospective study reports on the use of EUS-FNA in an unselected group of patients with mediastinal lymphadenopathy of unknown origin. Methods: The EUS database of a single tertiary referral centre was reviewed for patients who underwent EUS-FNA for mediastinal lymphadenopathy of unknown origin. Clinical presentation and imaging studies of each case were carefully reviewed and the diagnosis ''sarcoidosis'' or ''no sarcoidosis'' attributed if possible. The diagnoses were compared with the result of EUS-FNA. Results: One hundred and twenty four patients were investigated. In 35 cases EUS-FNA identified granulomas (group 1); in the other 89 cases (group 2) no granulomas were detected. The definite diagnoses in group 1 were sarcoidosis (n = 25), indefinite (n = 7), no sarcoidosis (n = 3). The definite diagnoses in group 2 were sarcoidosis (n = 3), indefinite (n = 9), no sarcoidosis (n = 77). Of the 77 cases with no sarcoidosis, 44 were diagnosed with other diseases. The other 33 showed non-specific changes in the FNA and sarcoidosis was excluded by negative non-EUS pathology (n = 17) and clinical presentation. The sensitivity and specificity for EUS-FNA were 89% (95% CI 82 to 94) and 96% (95% CI 91 to 98), respectively, after exclusion of the indefinite cases in both groups. Conclusions: EUS-FNA is an accurate method for diagnosing sarcoidosis in an unselected group of patients with mediastinal lymphadenopathy. The reported sensitivity and specificity must be appreciated in the context of the difficult and often incomplete clinical diagnosis of sarcoidosis.
The substitution of EUS for ERCP results in significant quantitative and qualitative change to ERCP practice, which has direct consequences for training and service development.
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