Publications by authors named "Achilles Demetriou"

Urologists and gynecologists manage most of the patients with female pelvic floor disorders. However, lack of a single focused approach among these two disciplines and other related fields may hinder advances in clinical care and research. Herein, along with describing the background of birth of the new subspeciality, we present a practical approach by which we established an integrated model of care and discovery for FPFD at our institution.

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The Patient Protection and Affordable Care Act signed into law in March 2010, has led to sweeping changes to the US health care system. The ensuing pace of change in health care regulation is unparalleled and difficult for physicians to keep up with. Because of the extraordinary challenges that have arisen, the public policy committee of the Society for Surgery of the Alimentary tract conducted a symposium at their 52nd Annual Meeting in May 2011 to educate participants on the myriad of public policy changes occurring in order to best prepare them for their future.

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Unlabelled: Liver stem cell (LSC) transplantation is a promising alternate approach to liver transplantation for patients with end-stage liver disease. However, the precise origin of LSCs remains unclear. Herein we determine if bone marrow mesenchymal stem cells (BMSCs) isolated from rats in acute hepatic failure (AHF) possess hepatic characteristics and have differentiation potential.

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Unlabelled: Liver tissue engineering with hepatic stem cells provides a promising alternative to liver transplantation in patients with acute and chronic hepatic failure. In this study, a three-dimensional (3D) bioscaffold was introduced for differentiation of rat bone marrow mesenchymal stem cells (BMSCs) into hepatocytes. For hepatocyte differentiation, third passage BMSCs isolated from normal adult F344 rats were seeded into collagen-coated poly(lactic-co-glycolic acid) (C-PLGA) 3D scaffolds with hepatocyte differentiation medium for 3 weeks.

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Previous studies have shown that bone marrow beta 2m(-)/Thy-1+ hepatic stem cells (BMHSCs) were able to engraft in vivo and differentiate into functioning hepatocytes in vitro. Our transcriptomic profiling on BMHSCs derived from rats subjected to common bile duct ligation (CBDL) demonstrated CBDL-derived beta 2m(-)/Thy-1+ BMHSCs expressed hepatocyte-like genes and shared more commonly expressed genes with hepatocytes, suggesting that an "on-site" priming of BMHSCs into hepatocyte lineage was initiated under the condition of CBDL. In this paper, transcriptomic profiling was carried out on livers from rats with CBDL to identify candidate factors released from cholestatic livers possibly involved in the priming of BMHSCs using Affymetrix Rat Genome U34A arrays.

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Background: Distinguishing those patients with fulminant hepatic failure (FHF) and who require transplantation from those FHF patients who will survive with receiving only intensive medical care remains problematic, and this distinction is important because of the chronic shortage of donor livers.

Methods: To assess the applicability of two prognostic scoring systems, referred to as the London and Clichy criteria, we compared using both systems, at the time of admission, for 43 FHF patients (15 M/28 F; age: 3716 yrs). Acetaminophen (ACM) was the etiology for 16 patients, while the remaining 27 had other etiologies.

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There is a need to develop artificial means of liver replacement and/or assistance with the aim of either supporting patients with borderline functional liver cell mass until their liver regenerates, or until a donor liver becomes available for transplantation. Selective plasma filtration is a novel approach to blood purification therapy designed to reduce the level of circulating toxins of hepatic and renal failure, mediators of inflammation and inhibitors of hepatic regeneration. The results of preclinical studies indicate that treatment of pigs with experimentally-induced fulminant hepatic failure is safe and effective in extending survival time and arresting brain swelling.

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In a previous investigation, we demonstrated that mesenchymal stem cells (MSCs) actively migrated to cardiac allografts and contributed to graft fibrosis and, to a lesser extent, to myocardial regeneration. The cellular/molecular mechanism responsible for MSC migration, however, is poorly understood. This paper examines the role of CD44-hyaluronan interaction in MSC migration, using a rat MSC line Ap8c3 and mouse CD44-/- or CD44+/+ bone marrow stromal cells (BMSCs).

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Pancreatic islet transplantation is limited by shortage of donor organs. Although beta-cell lines could be used, their secretion of insulin is characteristically glucose independent and immunoisolation is required. Here we show that intrasplenic transplantation of encapsulated glucose-responsive mouse insulinoma cells reversed streptozotocin (STZ)-induced diabetes in rats.

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Hepatocyte transplantation and use of bioartificial liver support systems have been suggested as potential therapies for fulminant hepatic failure. Cryopreservation in liquid nitrogen is presently the major method of long-term storage of isolated hepatocytes. However, cryopreservation can result in low cell recovery and reduction in differentiated function.

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Background: Pituitary tumor transforming gene (PTTG), homologous to a mammalian securin, plays a pivotal role in cell transformation, however, its biological function(s) in normal tissues is not fully understood. Because the liver is a regenerative organ, the relevant biological function of PTTG in the liver would be more feasible to understand PTTG. Also, PTTG may be involved in the liver regeneration.

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Background: Encapsulated cell therapy might be a promising approach to enable cell transplantation without immunosuppression. This study investigates the viability and hepatic function of hepatocytes encapsulated with alginate/poly-L-lysine in vitro and the effect of the intrasplenic transplantation of cultured encapsulated hepatocytes on survival in 90% hepatectomized rats as a preliminary step toward allogeneic hepatocyte transplantation without immunosuppression.

Materials And Methods: Rat hepatocytes were isolated and encapsulated using alginate/poly-L-lysine.

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The aim of the present study was to determine if the bone marrow (BM) beta2m-/Thy-1+ stem cells isolated from common bile duct ligated (CBDL) rats possess hepatocyte-like characteristics in their global gene expression profiles. The Affymetrix RG U34A arrays were used to conduct transcriptomic profiling on BM beta2m-/Thy-1+ stem cells isolated from CBDL and control rats as well as primary hepatocytes. Forty-one probe sets were up-regulated more than 2-fold in CBDL-derived beta2m-/Thy-1+ BM stem cells compared to control BM stem cells.

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Background: Several studies have identified beta2-microglobulin-negative (beta2M(-)) cells as a potential stem cell fraction in the bone marrow of rats and humans. We studied the ability of bone marrow-derived beta2M(-) cells to differentiate into cardiomyocytes and reconstitute the myocardium in a model of myocardial infarction.

Methods: beta2M(-) cells were purified from bone marrow of Lewis rats using a magnetic activated cell-sorting technique.

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Objective: The HepatAssist liver support system is an extracorporeal porcine hepatocyte-based bioartificial liver (BAL). The safety and efficacy of the BAL were evaluated in a prospective, randomized, controlled, multicenter trial in patients with severe acute liver failure.

Summary Background Data: In experimental animals with acute liver failure, we demonstrated beneficial effects of the BAL.

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Background: This study analyzes the prognostic significance of serum phosphorus in patients with acute liver failure (ALF).

Methods: We performed a retrospective analysis of 112 patients with ALF. Univariate and bivariate analyses based on Kaplan-Meier recovery curves and a multivariate Classification Tree Structure Survival Analysis were performed to identify independent predictors of outcome.

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Cell therapy is likely to succeed clinically if cells survive at the transplantation site and are protected against immune rejection. We hypothesized that this could be achieved with intrasplenic transplantation of encapsulated cells because the cells would have instant access to oxygen and nutrients while being separated from the host immune system. In order to provide proof of the concept, primary rat hepatocytes and human hepatoblastoma-derived HepG2 cells were used as model cells.

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Background: The definitive therapy for end-stage liver disease is orthotopic liver transplantation (OLT). However, rejection is still a major cause of mortality and morbidity following OLT. Hepatocyte transplantation has been used experimentally to treat liver diseases.

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Clinical islet transplantation (Tx) in type I diabetic patients has been successful so far only in a minority of cases, probably because of multiple factors, partly immunologic and partly nonimmunologic in nature. Preclinical studies of islet Tx in large animals are still needed to clarify the reasons and find possible solutions. In this study, we tested the feasibility of noninvasive, repeated intrahepatic allo-Tx of porcine pancreatic islets obtained from multiple donors, in pigs rendered diabetic by total pancreatectomy (Pct).

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It has been observed that liver regeneration in acute hepatic failure (AHF) is suppressed [Eguchi et al. Hepatology 1996;24(6):1452-9]. The molecular mechanism regulating this inhibition is not known.

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Background: In fulminant hepatic failure (FHF), the ability of surviving hepatocytes to proliferate is diminished. Therefore, it is important that medical therapy cause no further impairment of liver regeneration. In FHF, intracranial hypertension secondary to brain edema is the most common cause of brain injury and death and glycerol is used in some countries to treat this complication.

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