Risk-reducing appendectomy and the elimination of BRCA1-associated intraperitoneal cancer.

Risk-reducing bilateral salpingo-oophorectomy (RRBSO) and risk-reducing mastectomy are widely used for BRCA1 and BRCA2 mutation carriers to reduce the risk of ovarian and breast cancer. To our knowledge, no risk-reduction therapy has addressed the BCRA1/2 carrier lifetime risk of intra-abdominal peritoneal carcinoma from an appendix source. We identified a BRCA1 carrier in a hereditary breast and ovarian cancer kindred who developed a low-grade malignant appendiceal mucocele 2 years after risk-reducing salpingo-oophorectomy.

Role of endothelial nitric oxide synthase in the development of portal hypertension in the carbon tetrachloride-induced liver fibrosis model.

Portal hypertension (PHT) is a complication of liver cirrhosis and directly increases mortality and morbidity by increasing the propensity of venous hemorrhage. There are two main underlying causations for PHT, increased hepatic resistance and systemic hyperdynamic circulation. Both are related to localized aberrations in endothelial nitric oxide synthase (eNOS) function and NO biosynthesis.

Long-term effects on diet after proctocolectomy for ulcerative colitis.

Background: Patients with ulcerative colitis (UC) often report dietary intolerances. Our aim was to assess the effects of proctocolectomy (PC) for UC on dietary intolerances.

Methods: A novel disease-specific questionnaire was used.

Resveratrol inhibits expression and binding activity of the monocyte chemotactic protein-1 receptor, CCR2, on THP-1 monocytes.

Unlabelled: Monocyte chemotactic protein-1 and its receptor, CCR2, play a key role in atherosclerosis. We determined the effect of the polyphenol, resveratrol, on CCR2 and the mechanisms involved. Resveratrol treatment inhibited 125I-MCP-1 binding to THP-1 cells; 31, 56, 84% decrease for 10, 50 and 100 microM resveratrol, in the absence of any effect on receptor affinity.

Resveratrol, a polyphenolic phytostilbene, inhibits endothelial monocyte chemotactic protein-1 synthesis and secretion.

Background/aims: Resveratrol is a naturally occurring polyphenol phytoestrogen and one of several constituents of red wine thought to be cardioprotective. We investigated the effect of resveratrol on the expression of the atherogenic chemokine, monocyte chemotactic protein-1 (MCP-1).

Methods: Human umbilical vein endothelial cells were stimulated with interleukin-1beta (IL-1beta) in the absence or presence of resveratrol.

Ethanol inhibits pulse pressure-induced vascular smooth muscle cell migration by differentially modulating plasminogen activator inhibitor type 1, matrix metalloproteinase-2 and -9.

We investigated the effect of ethanol on the pulse pressure-induced expression of PAI-1 and MMP-2/9 in human smooth muscle cells (SMC). Human SMC were exposed to static or pulse pressure (25 mL/min; pulse pressure 106/50 mm Hg) conditions for 24 h in the absence or presence of ethanol (0.1-100 mM).

Ethanol inhibits monocyte chemotactic protein-1 expression in interleukin-1{beta}-activated human endothelial cells.

The aim of this study was to determine the effect of ethanol (EtOH) on endothelial monocyte chemotactic protein-1 (MCP-1) expression. IL-1beta increased the production of MCP-1 by human umbilical vein endothelial cells from undetectable levels to approximately 900 pg/ml at 24 h. EtOH dose-dependently inhibited IL-1beta-stimulated MCP-1 secretion as determined by ELISA: 25 +/- 1%, 35 +/- 7%, and 65 +/- 5% inhibition for 1, 10, and 100 mM EtOH, respectively, concomitant with inhibition of monocyte adhesion to activated endothelial cells.

A technique for emergency liver packing.

Control of liver hemorrhage may present a daunting clinical scenario. Use of liver packing techniques is highly effective to control bleeding but can result in significant recurrent bleeding with pack removal. Such bleeding is particularly a problem when large portions of the hepatic parenchymal surface and Glisson's capsule have been disrupted.

Two third-year medical student-level laboratory shock exercises without large animals.

Background: Historically, medical schools have taught principles of hemodynamic shock using large animal models. Such exercises are infrequent today due to the increasing aversion of students and the wider community to the use of large animals in teaching. Herein, we describe two alternative exercises that communicated basic science and clinical principles of shock effectively.

Pulse pressure-induced transmural fluid flux increases bovine aortic smooth muscle cell apoptosis in a mitogen activated protein kinase dependent manner.

Background: Mechanical forces associated with blood flow are critical in the regulation of vascular smooth muscle cell (VSMC) growth, migration, differentiation, and apoptosis as fundamental features in the pathogenesis of vascular disease. We investigated the effect of pulse pressure on VSMC apoptosis.

Methods: Using a perfused transcapillary co-culture system, bovine thoracic aortic SMC (BASMC) were exposed to increases in pulsatile flow (0.

Plasminogen activator inhibitor-1 deficiency enhances flow-induced smooth muscle cell migration.

Introduction: We determined the role of smooth muscle cell (SMC)-derived plasminogen activator inhibitor-1 (PAI-1) in the flow-induced SMC migratory response.

Materials And Methods: Wild type (wt) or PAI-1 knockout SMC were cultured in the absence or presence of endothelial cells (EC) under static or pulsatile flow conditions in a perfused culture system. SMC migration was then assessed by Transwell assay.

Eicosanoids in cirrhosis and portal hypertension.

In the last decade, the knowledge of the pathogenesis of portal hypertension and cirrhosis has increased dramatically. In portal hypertension, almost all the known vasoactive systems/substances are activated or increased and the most recent studies have stressed the importance of the endothelial factors, in particular, prostaglandins. Prostaglandins are formed following the oxygenation of arachidonic acid by the cyclooxygenase (Cox) pathway.

The role of nitric oxide synthase isoforms in extrahepatic portal hypertension: studies in gene-knockout mice.

Background & Aims: Considerable debate exists concerning which isoform of nitric oxide synthase (NOS) is responsible for the increased production of NO in PHT. We used the portal vein ligation model of PHT in wild-type and eNOS- or iNOS-knockout mice to definitively determine the contribution of these isoforms in the development of PHT.

Methods: The portal vein of wild-type mice, or those with targeted mutations in the nos2 gene (iNOS) or the nos3 gene (eNOS), was ligated and portal venous pressure (Ppv), abdominal aortic blood flow (Qao), and portosystemic shunt determined 2 weeks later.

Can ethanol therapies injure the bile ducts?

Administration of ethanol, whether applied directly to tissue or via an intra-arterial route, has been widely used to treat a variety of hepatic disorders, most importantly hepatocellular carcinoma. Animal studies, however, have demonstrated that intravascular hepatic ethanol therapy causes significant bile duct injury, and therefore, many centers have used intravascular ethanol applications with caution. A case of extensive bile duct injury in a 35-year-old female with a symptomatic hepatic hemangioma treated with ethanol embolization is presented.

Insulin-like growth factor I is a comitogen for hepatocyte growth factor in a rat model of hepatocellular carcinoma.

Hepatocyte growth factor-scatter factor (HGF-SF) is a potent hepatic mitogen yet inhibits hepatocellular carcinoma (HCC) cell growth in vitro. Insulin-like growth factor I (IGF-I) is a pleiotropic growth factor shown to be important in cell growth and differentiation in other tumors. We hypothesized that IGF-I may play a role in regulating HGF-SF activity and HCC progression.

Pulsatile flow-induced angiogenesis: role of G(i) subunits.

Objective: Angiogenesis plays a key role in the growth and function of normal and pathological tissues. We investigated the effect of pulsatile flow on endothelial cell (EC) in vitro angiogenic activity.

Methods And Results: Bovine aortic ECs were exposed to "static" or "flow" (1.

Ethanol differentially modulates the expression and activity of cell cycle regulatory proteins in rat aortic smooth muscle cells.

The aim of this study was to determine the effect of ethanol on cell cycle events during the G(1) and S phases in cultured vascular smooth muscle cells (VSMC). Flow cytometric analysis for the DNA content in rat aortic VSMC indicated that following ethanol treatment, the cell population in the G(0)/G(1) phase increased; 57.8+/-1.

Trends in long-term survival following liver resection for hepatic colorectal metastases.

Objective: To examine trends in outcomes of patients undergoing resection at a single tertiary care referral center over a 16-year period.

Summary Background Data: Hepatic resection is considered the treatment of choice in selected patients with colorectal metastasis confined to the liver. Although a variety of retrospective studies have demonstrated improvements in short-term outcomes in recent years, changes in long-term survival over time are less well-established.

Cryoablation of unresectable pancreatic cancer.

Background: Most patients with pancreatic cancer are not candidates for curative resection. The goal of this study was to evaluate the safety of an intraoperative ultrasound-guided cryosurgical procedure in a phase I study of unresectable pancreatic cancer.

Methods: From March 1995 to March 1999, 10 cryosurgeries using intraoperative ultrasound were performed on 9 patients with unresectable cancers at laparotomy.