The role of intraoperative cholangiogram in the management of patients recovering from acute biliary pancreatitis.

BACKGROUND: Use of the standard management for gallstone-associated acute pancreatitis calls for cholecystectomy with cholangiography performed during the same hospitalization after acute symptoms has decreased. No previous studies, however, have objectively addressed the usefulness of intraoperative cholangiography (IOC) for the management of this condition. This study aimed to determine the incidence of common bile duct (CBD) stones after an acute episode of gallstone pancreatitis. METHODS: The medical records of all patients who underwent a cholecystectomy and IOC after an episode of gallstone pancreatitis during the same admission between 1999 and 2004 at the University of Alberta and Royal Alexandra hospitals were examined to determine the incidence of CBD stones after resolution of gallstone pancreatitis. RESULTS: After a chart review for a series of 86 patients, 63 met the inclusion criteria. All except for one patient had undergone successful IOC (98%). Among the patients who had no evidence of CBD obstruction on preoperative imaging or lab work, three were found to have a filling defect on IOC and stones on their postoperative endoscopic retrograde cholangiopancreatography (ERCP) (3/63, 5%). This is not significantly different from the 4.6% incidence of CBD stones among patients with cholelithiasis who had normal preoperative imaging and blood work. CONCLUSION: In the setting of normal preoperative imaging and lab work, the incidence of CBD stones among patients recovering from acute mild to moderate gallstone pancreatitis is not significantly higher than among patients with no history of pancreatitis. Therefore, an IOC for post-gallstone pancreatitis does not alter management.

Mesohepatectomy.

BACKGROUND: Formal anatomic (lobar) or extended hepatectomies are recommended for liver malignancies located centrally within the liver (Couinaud's segments IVA, IVB, V, and VIII). Mesohepatectomy, resection of central hepatic segments and leaving the right and left segments in situ, removes large central tumors preserving more functioning liver tissue than either extended left or right hepatectomy. Mesohepatectomy is a seldom used, technically demanding procedure, and its application is yet to be defined. METHODS: Medical charts of 244 consecutive liver resection patients were reviewed retrospectively. Eighteen patients were treated with mesohepatectomy. Six patients had metastatic liver tumor (MLT), 11 had hepatocellular carcinoma (HCC), and 1 had gallbladder adenocarcinoma. The operative results were compared with groups of patients treated by lobar hepatectomy (n = 71) and extended left or right hepatectomy (n = 43). RESULTS: The mean mesohepatectomy operative time was 238 versus 304 minutes in the extended group. Inflow occlusion mean time was longer in the mesohepatectomy group than in extended procedures, 45 versus 39 minutes (P = not significant). Comparing the extended hepatectomy group, the mesohepatectomy group had a mean operative estimated blood loss 914 cc versus 1628 cc (P <0.01), postoperative hospital stay 9 versus 16 days (P = 0.054) and volume of resected liver 560cc versus 1500cc (P <0.01) respectively. The late complication rate was lower in the mesohepatectomy group than in the extended group and was comparable to the lobar hepatectomy group (P = 0.05). CONCLUSIONS: Despite its technical demands, mesohepatectomy should be considered as an alternative to extended hepatectomy for selected patients with primary and secondary hepatic tumors localized in middle liver segments, as its complication rate, postoperative recovery, and preserved liver tissue compare favorably with extended hepatic resection.

Ultrastructural correlates of quantal synaptic function at single CNS synapses.

We have tested the hypothesis that functional differences between synapses are associated with ultrastructure in cultured cortical neurons. Using Ca(2+) imaging, we measured NMDA receptor-mediated miniature synaptic calcium transients attributed to the spontaneous release of single transmitter quanta. After imaging, the identified neurons were processed for serial transmission electron microscopy. At sites of quantal NMDA receptor-dependent Ca(2+) transients, we confirmed the presence of excitatory synapses and measured spine size and synaptic contact area. Our results demonstrate that synapse size correlates positively with the amplitude of the NMDA receptor-mediated postsynaptic response, suggesting that larger synapses express a greater number of NMDA receptors. Therefore, regulation of quantal amplitude may involve processes that alter synapse size.

Restriction of peroxidase-mediated antibody reactivity to single neurons by local hydrogen peroxide production.

Current electrophysiological and imaging methods have begun to target the subcellular structure and function of single CNS neurons. Although physiological imaging methods now permit the resolution of activity of single presynaptic and postsynaptic elements, it has not been possible to unequivocally examine the array of proteins expressed at these same structures. This problem arises from the inability of current immunocytochemical techniques to differentiate between a process of the neuron of interest and the surrounding neuropil belonging to other cells. Thus, we have sought to develop an antibody staining method which would restrict reactivity to only a single neuron. Our assay involves preloading a single neuron with the coupling reagent biocytin. Following fixation, the injected biocytin is then complexed with avidin-linked glucose oxidase, providing a means of locally generating hydrogen peroxide within a cell of interest which catalyses the peroxidase-mediated (coupled to primary antibody) staining reaction. We have used this method successfully with antibodies to a number of neuronal markers (neuron-specific enolase, neurofilament, microtubule-associated protein and the glutamate receptor GluR2/3). Our staining method enables subcellular resolution of immunocytochemical markers within a single neuron without confounding staining of neighboring cells. We anticipate that this approach will facilitate the study of neuronal phenotype in fine dendritic processes in electrophysiologically characterized neurons in specimens with a complex neuropil, such as brain slices or high-density cultures.

Okadaic acid induces hyperphosphorylation of tau independently of mitogen-activated protein kinase activation.

Hyperphosphorylation of the microtubule-associated protein tau is a characteristic of Alzheimer brain tissue. Recent in vitro data suggest that mitogen-activated protein kinase (MAPK), a proline-directed protein kinase, phosphorylates the sites on tau common to Alzheimer's disease. Using an okadaic acid-induced tau hyperphosphorylation model, we have tested the requirement for MAPK activity, using a specific inhibitor ¿PD098059 [2-(2'-amino-3'-methoxyphenyl)oxanaphthalen-4-one]¿ of the MAPK activator Mek1. Mobility shift, phosphoepitope analysis, and direct measurement of kinase activity indicated that the Mek1 inhibitor dose-dependently blocked basal and okadaic acid-induced MAPK activation. Despite a block of MAPK activation by this inhibitor, robust tau hyperphosphorylation was observed in response to okadaic acid. In addition, activation of MAPK by phorbol 12-myristate 13-acetate did not result in tau phosphorylation, indicating that in primary cultures of cortical neurons elevated MAPK activity is not sufficient to induce tau hyperphosphorylation.