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Disease Context (disease + context)
Selected AbstractsReversible translocation of p115-RhoGEF by G12/13 -coupled receptorsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2008Bruno H. Meyer Abstract G protein-coupled receptors (GPCRs) are important targets for medicinal agents. Four different G protein families, Gs, Gi, Gq, and G12, engage in their linkage to activation of receptor-specific signal transduction pathways. G12 proteins were more recently studied, and upon activation by GPCRs they mediate activation of RhoGTPase guanine nucleotide exchange factors (RhoGEFs), which in turn activate the small GTPase RhoA. RhoA is involved in many cellular and physiological aspects, and a dysfunction of the G12/13 -Rho pathway can lead to hypertension, cardiovascular diseases, stroke, impaired wound healing and immune cell functions, cancer progression and metastasis, or asthma. In this study, regulator of G protein signaling (RGS) domain-containing RhoGEFs were tagged with enhanced green fluorescent protein (EGFP) to detect their subcellular localization and translocation upon receptor activation. Constitutively active G,12 and G,13 mutants induced redistribution of these RhoGEFs from the cytosol to the plasma membrane. Furthermore, a pronounced and rapid translocation of p115-RhoGEF from the cytosol to the plasma membrane was observed upon activation of several G12/13 -coupled GPCRs in a cell type-independent fashion. Plasma membrane translocation of p115-RhoGEF stimulated by a GPCR agonist could be completely and rapidly reversed by subsequent application of an antagonist for the respective GPCR, that is, p115-RhoGEF relocated back to the cytosol. The translocation of RhoGEF by G12/13 -linked GPCRs can be quantified and therefore used for pharmacological studies of the pathway, and to discover active compounds in a G12/13 -related disease context. J. Cell. Biochem. 104: 1660,1670, 2008. © 2008 Wiley-Liss, Inc. [source] Development of guidelines for the safe prescribing, dispensing and administration of cancer chemotherapyASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 3 2010Christine CARRINGTON Abstract Aim: The issue of medication safety is highly significant when anti-cancer therapy is used due to the high potential for harm from these agents and the disease context in which they are being used. This article reports on the development of multidisciplinary consensus guidelines for the safe prescribing, dispensing and administration of cancer chemotherapy undertaken by a working group of the Clinical Oncological Society of Australia (COSA). Methods: A working group of pharmacists, nurses and medical oncologists was convened from the COSA membership. A draft set of guidelines was proposed and circulated to the COSA council and the wider membership of COSA for comment. The final version of the guidelines was then distributed to 25 key stakeholders in Australia for feedback and endorsement. Results: An initial draft was developed based on existing standards, evidence from the literature and consensus opinion of the group. It was agreed that published case studies would be used as evidence for a particular statement where related processes had resulted in patient harm. The group defined 13 areas where a guidance statement was applicable to all professional disciplines and three individual sections based on the processes and the professionals involved in the provision of cancer therapy. Conclusion: The guidelines development represents a multidisciplinary collaboration to standardize the complex process of providing chemotherapy for cancer and to enhance patient safety. These are consensus guidelines based on the best available evidence and expert opinion of professionals working in cancer care. They should be seen as a point of reference for practitioners providing chemotherapy services. [source] The Clinical Oncological Society of Australia (COSA) guidelines for the safe prescribing, dispensing and administration of cancer chemotherapyASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 3 2010Christine CARRINGTON Abstract The issue of medication safety is highly significant when anti-cancer therapy is used as a treatment modality due to the high potential for harm from these agents and the disease context in which they are being used. These guidelines provide recommendations on the safe prescribing, dispensing and administration of chemotherapy and related agents used in the treatment of cancer. The guidelines represent a multidisciplinary collaboration to standardise the complex process of providing chemotherapy for cancer and to enhance patient safety. These are consensus guidelines based on the best available evidence and expert opinion of professionals working in cancer care. The aim of these guidelines is to assist in the prevention of medication errors and to improve patient safety with respect to the treatment of cancer. This guidance is intended for a multi-disciplinary audience and will have most relevance for medical, nursing and pharmacy staff involved in the complex processes of delivering chemotherapy and associated treatment. The scope of the guidelines includes; all patients and age groups receiving chemotherapy and targeted therapy for the treatment of cancer and cancer therapy administered by any route in both the hospital and home setting. These guidelines should be seen as point of reference for practitioners providing cancer chemotherapy services. [source] CMS oversight, OPOs and transplant centers and the law of unintended consequencesCLINICAL TRANSPLANTATION, Issue 6 2009Richard J. Howard Abstract:, The Health Resources and Services Administration launched collaboratives with the goals of increasing donation rates, increasing the number of organs transplanted, eliminating deaths on the waiting list and improving outcomes. The Center for Medicare and Medicaid Services (CMS) recently published requirements for organ procurement organizations (OPOs) and transplant centers. Failure to meet CMS performance measures could result in OPOs losing their service area or transplant centers losing their CMS certification. CMS uses analyses by the Scientific Registry of Transplant Recipients (SRTR) to evaluate a transplant center's performance based on risk-adjusted outcomes. However, CMS also uses a more liberal (one-sided) statistical test rendering more centers likely to qualify as low performing. Furthermore, the SRTR model does not incorporate some important patient variables in its statistical model which may result in biased determinations of quality of care. Cumulatively, there is much unexplained variation for transplant outcomes as suggested by the low predictive ability of survival models compared to other disease contexts. OPOs and transplant centers are unlikely to quietly accept their elimination. They may take certain steps that can result in exclusion of candidates who might otherwise benefit from transplantation and/or result in fewer transplants through restricted use of organs thought to carry higher risk of failure. CMS should join with transplant organizations to ensure that the goals of the collaborative are not inhibited by their performance measures. [source] | ||||||||||