The authors' goal was to determine the effects of specific binding and blockade of P- and E-selectins by a soluble P-selectin glycoprotein ligand-1 (PSGL-1) in rat models of hepatic in vivo warm ...ischemia and ex vivo cold ischemia. The authors also sought to determine the effect of selectin blockade on isograft survival in a syngeneic rat orthotopic liver transplant model.
Ischemia/reperfusion (I/R) injury is a major factor in poor graft function after liver transplantation, which may profoundly influence early graft function and late changes. It is hypothesized that I/R injury leads to the upregulation of P-selectin, which is then rapidly translocated to endothelial cell surfaces within 5 minutes of reperfusion of the liver, initiating steps leading to tethering of polymorphonuclear neutrophil leukocytes to the vascular intima. Local production by leukocytes of interleukin-1, tumor necrosis factor-alpha, or both induces P-selectin expression on the endothelium and continues the cascade of events, which increases cell adherence and infiltration of the organ.
To examine directly the effects of selectins in a warm hepatic I/R injury model, 100 microg of PSGL-1 or saline was given through the portal vein at the time of total hepatic inflow occlusion. The effects of PSGL-1 in cold ischemia were assessed using an isolated perfused rat liver after 6 hours of 4 degrees C storage in University of Wisconsin (UW) solution, with or without the instillation of PSGL-1 before the storage. To evaluate the effect of selectin blockade on liver transplant survival, syngeneic orthotopic liver transplants were performed between inbred male Sprague-Dawley rats after 24 hours of cold ischemic storage in UW solution. A separate group of animals received two doses of 100 microg of PSGL-1 through the portal vein before storage and before reperfusion of the transplanted liver. Recipient survival was assessed at 7 days, and the Kaplan-Meier product limit estimate method was used for univariate calculations of time-dependent recipient survival events.
In an in vivo warm rat liver ischemia model, perfusion with PSGL-1 afforded considerable protection from I/R injury, as demonstrated by decreased transaminase release, reduced histologic hepatocyte damage, and suppressed neutrophil infiltration, versus controls (p < 0.05). When cold stored livers were reperfused, PSGL-1 reduced the degree of hepatocyte transaminase release, reduced neutrophil infiltration, and decreased histologic hepatocyte damage (p < 0.05 vs. UW-only controls). On reperfusion, livers treated with PSGL-1 demonstrated increased portal vein blood flow and bile production (p < 0.05 vs. UW-only controls). In addition, 90% of the rats receiving liver isografts stored in UW solution supplemented with PSGL-1 survived 7 days versus 50% of those whose transplanted syngeneic livers had been stored in UW alone (p < 0.05).
Selectins play an important role in I/R injury of the liver. Early modulation of the interaction between P-selectin and its ligand decreases hepatocyte injury, neutrophil adhesion, and subsequent migration in both warm and cold rat liver ischemia models. In addition, the use of PSGL-1 before ischemic storage and before transplantation prevents hepatic injury, as documented by a significant increase in liver isograft survival. These findings have important clinical ramifications: early inhibition of alloantigen-independent mechanisms during the I/R damage may influence both short- and long-term survival of liver allografts.
Background: Common bile duct injuries occur in 0.2% to 0.8% of laparoscopic cholecystectomies (LC). Intraoperative cholangiograms (IOCG) are a useful means of detecting common bile duct injuries in ...the operating room.
Methods: Data were retrospectively reviewed for patients referred for management of common duct injuries from 1996 to 2000. Cost data were obtained from hospital records. Legal settlements were obtained from published sources.
Results: Twenty-one patients (0.133%) were found to have bile duct injuries and incurred median hospital stays of 11.5 days at an average cost of $587,491. The average cost of those requiring reoperation was $669,134. The 21 cases in our sample had total charges of $10,819,767. Performing IOCG during each LC in Orange County would have cost $10,669,725. If extrapolated to state and nationwide levels, the savings is far greater.
Conclusions: IOCG during LC is a cost-effective means of preventing the costs of delayed recognition of bile duct injuries.
The purpose of this study was to combine our clinical experience with a review of the literature to determine the value of orthotopic liver transplantation in the treatment of both boys and girls ...with ornithine transcarbamylase deficiency. Three boys younger than 1 year of age with symptomatic ornithine transcarbamylase deficiency (median age, 116 days; range, 40 to 223 days) underwent orthotopic liver transplantation. The patients' growth, developmental progress, ammonia levels, and amino acid levels were analyzed pre– and post–liver transplantation. The clinical courses of the respective patients and the treatment modalities used were compared with published reports from 1978 through 1997. The median follow‐up period in these 3 patients was 3.2 years (range, 9 months to 5.2 years). Orthotopic liver transplantation restored normal urea production and stabilized ammonia levels within 24 hours of surgery (median serum ammonia level 24 hours post–liver replacement, 43 μmol/L; range, 30 to 66 μmol/L). After liver replacement, arginine synthesis was normalized; however, plasma citrulline levels remained less than normal in all patients. Linear growth was evaluated in all 3 patients at the time of the most recent follow‐up; median z scores for patient height and weight were −2.16 and −1.16, respectively. Standardized intelligence tests showed that 2 of the 3 patients continue to perform at age‐appropriate levels. The third child was developmentally delayed pretransplantation at 4 months of age on presentation and continues to perform in a below‐average fashion. Orthotopic liver transplantation results in the restoration of normal urea production and serum ammonia levels in the boy suffering from symptomatic ornithine transcarbamylase deficiency. Serum arginine, but not citrulline, levels are normalized, probably because of the persistent intestinal mucosa defect. Patient growth is similar to that in infants undergoing liver transplantation for other causes. When liver transplantation is performed before cognitive impairment occurs, intellectual development is normal, because the risk of additional episodes of hyperammonemia is elevated.
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