The role of macrophages in the development of biliary injury in a lipopolysaccharide-aggravated hepatic ischaemia-reperfusion model.

INTRODUCTION: Endotoxins, in the form of lipopolysaccharides (LPS), are potent inducers of biliary injury. However the mechanism by which injury develops remains unclear. We hypothesized that hepatic macrophages are pivotal in the development of endotoxin-induced biliary injury and that no injury would occur in their absence. MATERIAL AND METHODS: Clodronate liposomes were used to deplete macrophages from the liver. Forty-eight rats were equally divided across six study groups: sham operation (sham), liposome treatment and sham operation (liposomes+sham), 1mg/kg LPS i.p. (LPS), liposome treatment and LPS administration (liposomes+LPS), hepatic ischaemia-reperfusion injury with LPS administration (IRI+LPS) and liposome treatment followed by IRI+LPS (liposomes+IRI+LPS). Following 6h of reperfusion, blood, bile, and liver tissue was collected for further analysis. Small bile duct injury was assessed, serum liver tests were performed and bile composition was evaluated. The permeability of the blood-biliary barrier (BBB) was assessed using intravenously administered horseradish peroxidase (HRP). RESULTS: The presence of hepatic macrophages was reduced by 90% in LPS and IRI+LPS groups pre-treated with clodronate liposomes (P<0.001). Severe small bile duct injury was not affected by macrophage depletion, and persisted in the liposomes+IRI+LPS group (50% of animals) and liposomes+LPS group (75% of animals). Likewise, BBB impairment persisted following macrophage depletion. LPS-induced elevation of the chemokine Mcp-1 in bile was not affected by macrophage depletion. CONCLUSIONS: Depletion of hepatic macrophages did not prevent development of biliary injury following LPS or LPS-enhanced IRI. Cholangiocyte activation rather than macrophage activation may underlie this injury. This article is part of a Special Issue entitled: Cholangiocytes in Health and Diseaseedited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.

Safe design of healthcare facilities.

The physical environment has a significant impact on health and safety; however, hospitals have not been designed with the explicit goal of enhancing patient safety through facility design. In April 2002, St Joseph's Community Hospital of West Bend, a member of SynergyHealth, brought together leaders in healthcare and systems engineering to develop a set of safety-driven facility design recommendations and principles that would guide the design of a new hospital facility focused on patient safety. By introducing safety-driven innovations into the facility design process, environmental designers and healthcare leaders will be able to make significant contributions to patient safety.

Stress and mTORture signaling.

The TOR (target of rapamycin) pathway is an evolutionarily conserved signaling module regulating cell growth (accumulation of mass) in response to a variety of environmental cues such as nutrient availability, hypoxia, DNA damage and osmotic stress. Its pivotal role in cellular and organismal homeostasis is reflected in the fact that unrestrained signaling activity in mammals is associated with the occurrence of disease states including inflammation, cancer and diabetes. The existence of TOR homologs in unicellular organisms whose growth is affected by environmental factors, such as temperature, nutrients and osmolarity, suggests an ancient role for the TOR signaling network in the surveillance of stress conditions. Here, we will summarize recent advances in the TOR signaling field with special emphasis on how stress conditions impinge on insulin/insulin-like growth factor signaling/TOR signaling.

Hospitals' newest challenge: designing in quality.

The job of producing high-quality products is even more difficult for health care providers than it is for those in manufacturing, where the quality movement began. As a part of the service industry, health care providers are in the position of producing products and delivering services at the moment of sale. Our task is to improve the quality of all of these simultaneous and interrelated processes. Traditionally, health care providers have made efforts to improve their products and services without realizing the impact that could be made by also improving resources, processes, and outcomes. This article is an overview of the new direction we have been taking: Retrospective review. Critical pathways. Building quality into all areas (resources, processes, products and services, and outcomes). Focused study of outcomes). We foresee a further evolution that will lead to exciting new methods for understanding and delivering high-quality care.

Health care trends lead to specialization of the MBA.

Four authors associated with St. Thomas University, John G. Reiling, M.B.A., John W. LaBree, M.D., Frederick J. "Fritz" Wenzel, FACMPE, and Carl Platou, M.B.A., write about how the changing nature of health care has fostered the need for a specialized Master of Business Administration in Medical Group Management degree program.