Pancreatitis: Preventing catastrophic haemorrhage.

Pancreatitis represents nearly 3% of acute admissions to general surgery in United Kingdom hospitals and has a mortality of around 1%-7% which increases to around 10%-18% in patients with severe pancreatitis. Patients at greatest risk were those identified to have infected pancreatic necrosis and/or organ failure. This review seeks to highlight the potential vascular complications associated with pancreatitis that despite being relatively uncommon are associated with mortality in the region of 34%-52%. We examine the current evidence base to determine the most appropriate method by which to image and treat pseudo-aneurysms that arise as the result of acute and chronic inflammation of pancreas. We identify how early recognition of the presence of a pseudo-aneurysm can facilitate expedited care in an expert centre of a complex pathology that may require angiographic, percutaneous, endoscopic or surgical intervention to prevent catastrophic haemorrhage.

Evolving management of metaplasia and dysplasia in Barrett's epithelium.

Oesophageal cancer affects more than 450000 people worldwide and despite continued medical advancements the incidence of oesophageal cancer is increasing. Oesophageal cancer has a 5 year survival of 15%-25% and now globally attempts are made to more aggressively diagnose and treat Barrett's oesophagus the known precursor to invasive disease. Currently diagnosis the of Barrett's oesophagus is predominantly made after endoscopic visualisation and histopathological confirmation. Minimally invasive techniques are being developed to improve the viability of screening programs. The management of Barrett's oesophagus can vary greatly dependent on the presence and severity of dysplasia. There is no consensus between the major international medical societies to determine and agreed surveillance and intervention pathway. In this review we analysed the current literature to demonstrate the evolving management of metaplasia and dysplasia in Barrett's epithelium.

An in vivo model of ischaemia-reperfusion injury and ischaemic preconditioning in the mouse heart.

INTRODUCTION: Our aim was to develop a robust protocol for inducing ischaemia-reperfusion injury and preconditioning in the in vivo mouse heart. METHODS: Animals were prepared by standard techniques adapted for the mouse. RESULTS: Thirty minutes of ischaemia appeared to strike the most appropriate balance between large infarct volumes with the risk of heart failure and excessively small infarcts. With this duration of ischaemia, a protocol of three sets of 5 min of ischaemia and 5 min of reperfusion was found to precondition, leading to significantly smaller infarct sizes (infarct volume: risk zone volume reduced to 10.1 +/- 2.7% from 41.39% +/- 3.0; P < .05, n = 6 and 7, respectively). Late preconditioning also occurred (infarct volume: risk zone volume = 57.9 +/- 10.1% vs. 35.4 +/- 4.2%, sham compared to late preconditioning, respectively; P = .001, n = 7). DISCUSSION: Whilst further refinements may indeed be possible, we feel this article details a valuable, robust protocol for in vivo studies of ischaemia-reperfusion injury and preconditioning in the mouse heart.

MAPKAPK-2 modulates p38-MAPK localization and small heat shock protein phosphorylation but does not mediate the injury associated with p38-MAPK activation during myocardial ischemia.

MAPKAPK-2 (MK2) is a protein kinase activated downstream of p38-MAPK which phosphorylates the small heat shock proteins HSP27 and alphaB crystallin and modulates p38-MAPK cellular distribution. p38-MAPK activation is thought to contribute to myocardial ischemic injury; therefore, we investigated MK2 effects on ischemic injury and p38 cellular localization using MK2-deficient mice (KO). Immunoblotting of extracts from Langendorff-perfused hearts subjected to aerobic perfusion or global ischemia or reperfusion showed that the total and phosphorylated p38 levels were significantly lower in MK2(-/-) compared to MK2(+/+) hearts at baseline, but the ratio of phosphorylated/total p38 was similar. These results were confirmed by cellular fractionation and immunoblotting for both cytosolic and nuclear compartments. Furthermore, HSP27 and alphaB crsytallin phosphorylation were reduced to baseline in MK2(-/-) hearts. On semiquantitative immunofluorescence laser confocal microscopy of hearts during aerobic perfusion, the mean total p38 fluorescence was significantly higher in the nuclear compared to extranuclear (cytoplasmic, sarcomeric, and sarcolemmal compartments) in MK2(+/+) hearts. However, although the increase in phosphorylated p38 fluorescence intensity in all compartments following ischemia in MK2(+/+) hearts was lost in MK2(-/-) hearts, it was basally elevated in nuclei of MK2(-/-) hearts and was similar to that seen during ischemia in MK2(+/+) hearts. Despite these differences, similar infarct volumes were recorded in wild-type MK2(+/+) and MK2(-/-) hearts, which were decreased by the p38 inhibitor SB203580 (1 microM) in both genotypes. In conclusion, p38 MAPK-induced myocardial ischemic injury is not modulated by MK2. However, the absence of MK2 perturbs the cellular distribution of p38. The preserved nuclear distribution of active p38 MAPK in MK2(-/-) hearts and the conserved response to SB203580 suggests that activation of p38 MAPK may contribute to injury independently of MK2.

Varying susceptibility to myocardial infarction among C57BL/6 mice of different genetic background.

Genetically manipulated mouse lines are invaluable to investigate the effects of a single gene on sensitivity to ischemia. When choosing appropriate controls, we were concerned that intrinsic, strain-independent but colony-dependent differences may influence the susceptibility to ischemia. We, therefore, compared the infarct:risk volume ratio (I:R%) after 30-min global ischemia in Langendorff-perfused hearts from outbred C57BL/6 mice with that in wild-type mice derived from heterozygote x heterozygote crosses of two different in-house C57BL/6 mouse lines with targeted disruption of an MKK3 or MAPKAPK2 allele. Despite similar hemodynamic characteristics, I:R% in outbred C57BL/6 hearts was significantlysmaller (40.8 +/- 2.8%) than in C57BL/6 MAPKAPK2 wild types (65.8 +/- 4.5%, P = 0.0003) and significantly larger than in C57BL/6 MKK3 wild types (23.7 +/- 2.9%, P = 0.002). Therefore, inherent colony substrain-dependent differences appear to influence the susceptibility to infarction in response to global ischemia, underscoring the importance of using colony-matched wild-type controls in murine studies of myocardial ischemia.