Librarians support clinical and educational missions of medical centers through their availability to assist with the acquisition of information and materials on an "as reported" basis. We sought to integrate the librarian more fully into clinical care and clinical education in a teriary children's hospital. We began with three clinical divisions, each with unique needs, and developed a system of web-based materials that can be managed to deliver patient information to specific groups of people.
Poster presentation. Abstract: Purpose. Sphingosine kinases (SKs) phosphorylate sphingosine to create sphingosine 1 phosphate (S1P), which is involved in cell survival, proliferation, motility, and inflammation via intracellular signaling through release of Ca2+ stores, activation of NF??B, and extracellular interactions with G protein-coupled receptors (S1P receptors 1-5). Inhibitors of SK1 have been used successfully to treat experimental murine inflammatory bowel disease, diabetic retinopathy, and rheumatoid arthritis. SK1 is expressed in mesangial cells and plays a role in mesangial cell migration. The role of SKs in promoting inflammation in lupus is unknown. We hypothesized that ABC294640 (ABC), an orally available SK inhibitor, would reduce markers of glomerular pathology in the MRL/MpJTnfrsf6lpr/ J (MRL/lpr) murine model of lupus. Methods. Eleven MRL/lpr mice were treated with either polyethylene glycol (PEG, n=5) or ABC in PEG (50 mg/kg/day, n=6) from 10 (before onset of disease) to 20 weeks of age (significant albuminuria present). Urine was collected every other week and analyzed for albumin. Moribund mice were sacrificed, and all measures were carried forward. At 20 weeks, kidney and total weights were determined. Renal, skin, and joint tissue were harvested for histopathological scoring, while renal tissue was stained for IgG/C3 deposition and examined by electron microscopy. Serum anti-double stranded DNA antibody levels were determined at 20 weeks. Urine thromboxane levels were determined at 16 weeks. Spleen cell subsets were determine by flow cytometry. Differences between groups were determined by t-test or Wilcoxon rank sum analysis. Results were reported as averages standard error. Results. Survival was greater in ABC-treated mice than controls (100 vs. 40% at 20 weeks). By 18 and 20 weeks, proteinuria was lower in ABC-treated mice than control mice (106 vs. 3818 and 191 vs. 6021). Kidney/total body weights were significantly lower in ABC-treated mice than controls (1.50.1 vs. 2.20.1 mg/g, p=0.001). There was a trend towards lower renal thromboxane production in treated mice. Renal and cutaneous pathologic scores were lower
in treated mice. Neither anti-double stranded DNA antibody production nor basement membrane and mesangial IgG/C3 staining were different between groups. Spleen marginal zone B cells were greater in treated mice. Conclusions. ABC294640 treatment improves survival, possibly due to reduced renal failure
and vasculitis. ABC294640 treatment reduces often clinically refractory necrotic/crescentic glomerular lesions associated with reduced renal function in humans, making SK an attractive target for investigation as adjunctive therapy ABC294640 treatment reduces podocyte flattening associated with nephrotic
range proteinuria in humans, making SK a possible target for investigation as adjunctive therapy in membranous nephritis with nephrotic range proteinuria. Improvements in outcomes are independent of changes in production and deposition of nephritic autoantibodies. We hypothesize that inhibition of SK
may reduce homing of inflammatory cells and activation of resident and inflammatory cells to produce inflammatory mediators such as thromboxane.
Abstract: Residents in the Department of Pediatrics at the Medical University of South Carolina (MUSC) participate in an intensive program to learn the practice of Evidence-Based Medicine (EBM). This is a unique "redident-powered" program that includes hands-on weekly sessions to answer clinical questions using EBM, formulating and answering EBM questions with a librarian during rounds, and a dedicated group of faculty that serve as team leaders and mentors. In their last years, residents create their own evidence by doing a capstone research project.