Flow cytometry offers great potential for the study of xenobiotic metabolism in intact cells. We explored this application by the use of ethoxyfluorescein ethyl ester (EFEE) and isolated rat hepatocytes, a classic system for studying such reactions. EFEE is only weakly fluorescent and it diffuses freely into viable cells, where it is metabolized to fluorescein by a process dependent upon mixed-function oxidase activity. In the current study, viable hepatocytes were first identified by flow cytometric assessment of fluorescein diacetate staining. The viable subpopulation was also identifiable on the basis of forward and right angle light scattering properties alone, and it was in this fraction that EFEE metabolism was measured. Metabolism of EFEE to fluorescein was quantified by flow cytometry. SKF 525A, alpha-naphthoflavone, and metyrapone, classic inhibitors of mixed-function oxidation, each inhibited the metabolism of EFEE. These results demonstrate the potential of EFEE for use in flow cytometric studies of drug metabolism, such as in multiparameter mechanistic assays of cellular xenobiotic metabolism and toxicity, and in the isolation by fluorescence-activated cell sorting of subpopulations which differ in this activity.
Sepsis affects 18 million people worldwide every year, and on average each case costs more than US$22 000 to treat. Despite this there is no consensus on the clinical definition of sepsis, and successful diagnosis and treatment is difficult. The Barcelona Declaration, issued by the Surviving Sepsis Campaign in October 2002, outlines a six-point plan to reduce the relative mortality of sepsis by 25% over the next 5 years. The Campaign organizers are currently producing evidence-based guidelines on source control and management of sepsis, as well as a policy document on how sepsis is managed around the world.
A significant number of surgical patients are at risk of intra- or post-operative complications or both, which are associated with increased lengths of stay, costs, and mortality. Reducing these risks is important for the individual patient but also for health-care planners and managers. Insufficient tissue perfusion and cellular oxygenation due to hypovolemia, heart dysfunction or both is one of the leading causes of perioperative complications. Adequate perioperative management guided by effective and timely hemodynamic monitoring can help reduce the risk of complications and thus potentially improve outcomes. In this review, we describe the various available hemodynamic monitoring systems and how they can best be used to guide cardiovascular and fluid management in the perioperative period in high-risk surgical patients.
SCOPUS: ed.j
We found that the CMQCC admission risk assessment criteria stratified women by increasing rates of severe postpartum hemorrhage in our sample, which enables early preparation for many postpartum hemorrhages. However, the CMQCC risk factors missed a substantial proportion of postpartum hemorrhages. Efforts to improve postpartum hemorrhage risk assessment using present-on-admission risk factors should consider inclusion of other nonobstetrical factors.