A cytoplasmic peptide of the neurotrophin receptor p75NTR: induction of apoptosis and NMR determined helical conformation

AbstractThe neurotrophin receptor (NTR) and tumor necrosis factor receptor family of receptors regulate apoptotic cell death during development and in adult tissues [Beutler and van Huffel, Science 264 (1994) 667–668]. We have examined a fragment of p75NTR from the carboxyl terminus of the receptor and a variant form of this peptide via NMR techniques and in vitro assays for apoptotic activity. The wild type peptide induces apoptosis and adopts a helical conformation oriented parallel to the surface of lipid micelles, whereas the variant form adopts a non-helical conformation in the presence of lipid and shows no activity. These experiments suggest a link between structure and function of the two peptides

TEG® and RapidTEG® are unreliable for detecting warfarin-coagulopathy: a prospective cohort study

BACKGROUND: Thromboelastography® (TEG) utilizes kaolin, an intrinsic pathway activator, to assess clotting function. Recent published studies suggest that TEG results are commonly normal in patients receiving warfarin, despite an increased International Normalized Ratio (INR). Because RapidTEG™ includes tissue factor, an extrinsic pathway activator, as well as kaolin, we hypothesized that RapidTEG would be more sensitive in detecting a warfarin-effect. METHODS: Included in this prospective study were 22 consecutive patients undergoing elective cardioversion and receiving warfarin. Prior to cardioversion, blood was collected to assess INR, Prothrombin Time, TEG, and RapidTEG. RESULTS: INR Results: 2.8 ± 0.5 (1.6 to 4.2). Prothrombin Time Results: 19.1 ± 2.2 (13.9. to 24.3). TEG Results (Reference Range): R-Time: 8.3 ± 2.7 (2–8); K-Time: 2.1 ± 1.4 (1–3); Angle: 62.5 ± 10.3 (55–78); MA: 63.2 ± 10.3 (51–69); G: 9.4 ± 3.5 (4.6-10.9); R-Time within normal range: 10 (45.5%) with INR 2.9 ± 0.3; Correlation coefficients for INR and each of the 5 TEG variables were insignificant (P > 0.05). RapidTEG Results (Reference Range): ACT: 132 ± 58 (86–118); K-Time: 1.2 ± 0.5 (1–2); Angle: 75.4 ± 5.2 (64–80); MA: 63.4 ± 5.1 (52–71); G: 8.9 ± 2.0 (5.0-11.6); ACT within normal range: 9 (40.9%) with INR 2.7 ± 0.5; Correlation coefficients for INR and each of the 5 RapidTEG variables were insignificant (P > 0.05). CONCLUSIONS: TEG, using kaolin activation, and RapidTEG, with kaolin and tissue factor activation, were normal in a substantial percent of warfarin patients, despite an increased INR. The false-negative rate for detecting warfarin coagulopathy with either test is unacceptable. The lack of correlation between INR and all TEG and RapidTEG components further indicates that these methodologies are insensitive to warfarin effects. Findings suggest that intrinsic pathway activation may mitigate detection of an extrinsic pathway coagulopathy

Pentosan polysulfate increases affinity between ADAMTS-5 and TIMP-3 through formation of an electrostatically driven trimolecular complex

The semi-synthetic sulfated polysaccharide PPS (pentosan polysulfate) increases affinity between the aggrecan-degrading ADAMTSs (adamalysins with thrombospondin motifs) and their endogenous inhibitor, TIMP (tissue inhibitor of metalloproteinases)-3. In the present study we demonstrate that PPS mediates the formation of a high-affinity trimolecular complex with ADAMTS-5 and TIMP-3. A TIMP-3 mutant that lacks extracellular-matrix-binding ability was insensitive to this affinity increase, and truncated forms of ADAMTS-5 that lack the Sp (spacer) domain had reduced PPS-binding ability and sensitivity to the affinity increase. PPS molecules composed of 11 or more saccharide units were 100-fold more effective than those of eight saccharide units, indicating the involvement of extended or multiple protein-interaction sites. The formation of a high-affinity trimolecular complex was completely abolished in the presence of 0.4 M NaCl. These results suggest that PPS enhances the affinity between ADAMTS-5 and TIMP-3 by forming electrostatically driven trimolecular complexes under physiological conditions

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Percentage of all facilities with each operational characteristic for orthopaedics

<p><b>Copyright information:</b></p><p>Taken from "United States level I trauma centers are not created equal – a concern for patient safety?"</p><p>http://www.pssjournal.com/content/2/1/18</p><p>Patient Safety in Surgery 2008;2():18-18.</p><p>Published online 21 Jul 2008</p><p>PMCID:PMC2515286.</p><p></p

Percentage of all facilities with each operational characteristic for trauma

<p><b>Copyright information:</b></p><p>Taken from "United States level I trauma centers are not created equal – a concern for patient safety?"</p><p>http://www.pssjournal.com/content/2/1/18</p><p>Patient Safety in Surgery 2008;2():18-18.</p><p>Published online 21 Jul 2008</p><p>PMCID:PMC2515286.</p><p></p