bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early Mobilization of Operatively Fixed Ankle Fractures: A Systematic Review
Authors: Thomas Gethin , Whalley Helen , Modi Chetan 
Published: July 2009

Background: It is commonly believed that early motion after joint fixation is advantageous, especially in the upper limb. In the ankle joint this is much less clear. No previous systematic review of the evidence for this could be found in the literature. Materials and Methods: Nine randomized control trials were identified which met the inclusion criteria and compared early motion of the ankle joint to immobilization in a cast for 6 weeks. These varied in quality and numbers. All treated patients equally in all other respects including weight bearing. Where outcome measures were similar, some data pooling was possible. Results: There is good evidence that early motion is associated with a quicker return to work on average ( p = 0.008) and also with an improved range of motion at 12 weeks (dorsiflexion p = 0.001; plantarflexion p < 0.00001) compared to cast immobilization. However it is also associated with an increased risk of wound infection ( p = 0.002). There is a suggestion that early motion results in a lower rate of deep vein thrombosis ( p = 0.12). There is no evidence that it results in improved joint specific outcome scores or range of motion at 1 year. Conclusion: It is difficult to conclude whether early motion is overall better or worse than cast immobilization. The evidence suggests however that a young fit patient who needs to return to work may benefit from early motion of the ankle joint whereas a patient with poor skin or at risk of infection may be better treated in a cast after surgery. Level of Evidence: I, Systematic Review of Level I-II Studies
Arthroscopic Lateral Release and Percutaneous Distal Osteotomy for Hallux Valgus: A Preliminary Report
Authors: Siclari Alberto , Decantis Vito 
Published: July 2009

Distal osteotomy of the first metatarsal is frequently used for the treatment of hallux valgus deformity. The great toe arthroscopy is a safe procedure to perform a distal soft tissue release and a complete evaluation of the first metatarsal-phalangeal joint. The aim of this study was to evaluate the results of the arthroscopic distal soft tissue release with a distal percutaneous osteotomy in the treatment of hallux valgus deformity. From January 1, 2003, to August 1, 2006, 59 consecutive procedures were performed in 49 patients. Clinical evaluation was calculated using the hallux score of the American Orthopedic Foot and Ankle Society (AOFAS). The mean follow up was 31.48 (range, 12 to 48) months and the AOFAS score improved from 45 (range, 30 to 65) points to 90.61 (range, 75 to 100). The excellent results obtained encourage the authors to go on treat the hallux valgus deformity with this combination of two minimal invasive procedures. Level of Evidence: IV, Retrospective Case Series
Minimally Invasive Paratenon Release for Non-Insertional Achilles Tendinopathy
Authors: Naidu Venunatha , Abbassian Ali , Nielsen Dominic , Uppalapati Raju , Shetty Anupkumar 
Published: July 2009

Background: Non-insertional Achilles tendinopathy is an increasing, perhaps secondary to an increase in sporting activities. Traditional open surgical procedures have been associated with a significant rate of complications. We describe a minimally invasive technique involving the release of the adherent paratenon with a peritendinous infusion of corticosteroids and present the results in a cohort of patients. Materials and Methods: Twenty-nine tendons (26 patients) with non-insertional Achilles tendinopathy were treated with the above technique. Assessments were made prospectively using an adapted classification of Achilles tendon disability and a visual analogue scale for pain. Patients were interviewed in person or by telephone at an average of 14 (range, 6 to 30) months after surgery. Results: The average pain score (VAS) improved from 8.7 to 2.4 ( p < 0.001) and the average Puddu level of disability improved from 4.9 to 1.7 ( p < 0.001). Seventy-five percent of patients had a good or excellent outcome with 20% having sufficient improvement not to pursue further medical attention for their tendinopathy. There was a 7% rate of minor complications due to delayed wound healing which resolved spontaneously and did not affect the rehabilitation or the recovery of the patients. Conclusion: A minimally invasive circumferential paratenon release and peritendinous steroid infusion was a simple method to treat non-insertional Achilles tendinopathy and had low morbidity in our series. This technique has become our preferred primary surgical intervention for this condition. Level of Evidence: IV, Retrospective Case Series
Locally Generated Bone Slurry Accelerated Ankle Arthrodesis
Authors: Wheeler Jacynda , Sangeorzan Adam , Crass Sarah M. , Sangeorzan Bruce J. , Benirschke Stephen K. , Hansen Sigvard T. 
Published: July 2009

Background: Reported ankle fusion healing times vary between 7 to 72 weeks. High non-union and delayed union rates have led to an increased use of bone graft and bone graft substitutes. It was our goal to see if addition of a bone slurry could accelerate the rate of healing. Materials and Methods: We compared the radiographic healing after ankle arthrodesis in two groups of patients treated over 3 years with and without a ‘bone slurry.’ In group one, a slurry of bone particles was generated with a low-speed burr and left in the joint before internal fixation. Group two had similar fixation but no bone slurry. Two reviewers, blinded to the presence or absence of slurry, studied magnified digital radiographs at 6 and 12 weeks. The percentage of the joint bridged by bone was recorded for each and the groups were averaged. Groups were compared using Wilcoxon rank sum. Results: There were 32 patients in group one and 22 in group two. Groups were similar in age, gender and diagnosis. At 6 weeks, group one had 94.1% bridging bone, as measured on AP radiographs. Group two had 76.4% bridging bone. (Wilcoxon rank sum test p = 0.0099). At 12 weeks, group one had 98.1% bridging bone and group two had 85.7% bridging bone (Wilcoxon rank sum test p = 0.026). Conclusion: Use of a low-speed burr to generate a “bone paste” from the local bone surfaces was associated with an increased percentage of healed bone surface at 6 and 12 weeks in patients undergoing ankle arthrodesis. Level of Evidence: III, Retrospective Case Control
Accuracy of Anterolateral Drawer Test in Lateral Ankle Instability: A Cadaveric Study
Authors: Phisitkul Phinit , Chaichankul Chaisiri , Sripongsai Ratthapol , Prasitdamrong Ittipol , Tengtrakulcharoen Pannipa , Suarchawaratana Siripim 
Published: July 2009

Background: In the assessment of lateral ankle instability, the anterior drawer test has been found to be inaccurate and the focus on pure anterior translation cannot properly perceive the anterolateral rotatory nature of the talar displacement. In order to address this, the anterolateral drawer test can be done with digital palpation of the talar displacement anterolaterally with a controlled angle of plantarflexion as well as application of the translational force. Materials and Methods: We evaluated the anterolateral drawer test and the original anterior drawer test in 10 fresh below-the-knee specimens using a direct anatomic measurement (DAM) loaded by a Telos stress device as a reference. Specimens were assigned into three groups: intact ligaments, ATFL-cut, and ATFL&CFL-cut. The examiners were blinded with one performing the anterolateral drawer test (E1) while the other performed the original anterior drawer test (E2). Results: Pearson's correlation coefficient indicated a statistically significant linear relationship between DAM/E1 r = 0.931, p < 0.001 but not between DAM/E2 r = 0.519, p = 0.124. Intraclass correlation coefficient show correlation between DAM/E1 and DAM/E2 to be 0.945 ( p < 0.001) and 0.683 ( p = 0.051). When 3 mm or more was used as the threshold to diagnose a lateral ligament rupture, sensitivity and specificity were E1(100%, 100%) and E2(75%, 50%). Conclusion: The anterolateral drawer test showed high accuracy in the determination of lateral ankle instability and in the diagnosis of a ligament rupture. Clinical Relevance: Further investigation regarding the accuracy and reliability of this test in comparison with the original anterior drawer test is warranted in a patient population with ankle instability.
Comparison of Augmentation Methods for Internal Fixation of Osteoporotic Ankle Fractures
Authors: Panchbhavi Vinod K. , Vallurupalli Santaram , Morris Randal 
Published: July 2009

Background: Internal fixation of osteoporotic ankle fractures is associated with failure of fixation. This study compared different augmentation methods biomechanically. Materials and Methods: In nine paired fresh-frozen cadaver legs, an identical supination-external rotation type II ankle fracture was created. Fractures were stabilized using an eight-hole locking plate. In four pairs, two screws were inserted across the syndesmosis for purchase in the tibial metaphysis. One leg from each pair was randomly selected for injection of calcium sulphate-calcium phosphate graft into the screw holes. Each leg was mounted to an MTS machine in a custom loading frame. Axial cyclic loading to body weight was performed to measure displacement at the fracture site, followed by rotational loading to failure simulating a supination external rotation injury. Data were analyzed using a two-way paired t -test and ANOVA. Results: The specimens used had a mean bone mineral density of 0.49 ± 0.15 (SD) g/cm2, and a mean age of 83 ± 12 years. In the biomechanical tests, there were no significant differences between augmented and non-augmented locking plates without the tibia-pro-fibula screws in axial stiffness ( p = 0.10), external rotation angle at failure ( p = 0.42), failure torque ( p = 0.57), energy absorbed before failure ( p = 0.47), and motion at the fracture site with cyclic axial loading ( p = 0.15). There were no significant differences between augmented and non-augmented locking plates with the tibia-pro-fibula screws in the external rotation angle at failure ( p = 0.83), failure torque ( p = 0.58), and failure energy ( p = 0.4). However, the overall strength of the fixation tended to increase with tibia-pro-fibula screws and augmentation. Conclusion: Internal fixation of an osteoporotic lateral malleolar fracture using a locking plate and screws provided a construct comparable in strength to that augmented with calcium sulfate-calcium phosphate graft and/or tibia-pro-fibula screws. Clinical Relevance: Strategies to augment internal fixation of osteoporotic ankle fractures may minimize risk for failure of fixation and may enable early weight bearing mobilization and return to function in elderly patients.
Deletion of the C-Terminal Region of Dengue Virus Nonstructural Protein 1 (NS1) Abolishes Anti-NS1-Mediated Platelet Dysfunction and Bleeding Tendency
Authors: Chen Mei-Chun , Lin Chiou-Feng , Lei Huan-Yao , Lin Shih-Chao , Liu Hsiao-Sheng , Yeh Trai-Ming , Anderson Robert , Lin Yee-Shin 
Published: July 2009

Abstract
The mechanisms underlying dengue hemorrhagic disease are incompletely understood. We previously showed that anti-dengue virus (DV) nonstructural protein 1 (NS1) Abs cross-react with human platelets and inhibit platelet aggregation. Based on sequence homology alignment, the cross-reactive epitopes reside in the C-terminal region of DV NS1. In this study, we compared the effects of Abs against full-length DV NS1 and NS1 lacking the C-terminal aa 271 to 352 (designated ΔC NS1). Anti-ΔC NS1 Abs exhibited lower platelet binding activity than that of anti-full-length NS1. Anti-full-length NS1 but not anti-ΔC NS1 Abs inhibited platelet aggregation, which was shown to involve integrin αIIbβ3 inactivation. We found that the bleeding time in full-length NS1-hyperimmunized mice was longer than that in the normal control mice. By contrast, ΔC NS1-hyperimmunized mice showed a bleeding time similar to that of normal control mice. Passively administered anti-DV NS1, but not anti-ΔC NS1, Ab level decreased markedly in serum and this decrease was correlated with Ab binding to platelets. A transient platelet loss in the circulation was observed after anti-DV NS1, but not anti-ΔC NS1, Ab administration. In summary, platelet dysfunction and bleeding tendency are induced by anti-full-length DV NS1 but not by anti-ΔC NS1 Abs. These findings may be important not only for understanding dengue hemorrhagic disease pathogenesis but also for dengue vaccine development.
Recurrence of Intracranial Tumors following Adoptive T Cell Therapy Can Be Prevented by Direct and Indirect Killing Aided by High Levels of Tumor Antigen Cross-Presented on Stromal Cells
Authors: Thomas Diana L. , Kim Miri , Bowerman Natalie A. , Narayanan Samanthi , Kranz David M. , Schreiber Hans , Roy Edward J. 
Published: July 2009

Abstract
Elimination of peripheral tumors by adoptively transferred tumor-specific T cells may require killing of cancer cells and tumor stromal cells. Tumor Ags are cross-presented on stromal cells, resulting in direct cytotoxic T cell (CTL) killing of both Ag-expressing cancer cells and stromal cells. Indirect killing of Ag loss variant cells also occurs. We show here that similar processes occur in a brain tumor stromal environment. We used murine cancer cell lines that express high or low levels of a peptide Ag, SIYRYYGL (SIY), recognized by transgenic 2C CD8+ T cells. The two cell lines are killed with equivalent efficiency by 2C T cells in vitro. Following adoptive transfer of 2C T cells into mice with established SIY-Hi or SIY-Lo brain tumors, tumors of both types regressed, but low-Ag-expressing tumors recurred. High-Ag-expressing tumors contained CD11b+ cells cross-presenting SIY peptide and were completely eliminated by 2C T cells. To further test the role of cross-presentation, RAG1−/− H-2b mice were infused with H-2k tumor cells expressing high levels of SIY peptide. Adoptively transferred 2C T cells are able to kill cross-presenting H-2b stromal cells but not H-2k tumor cells. In peripheral models, this paradigm led to a small static tumor. In the brain, activated 2C T cells were able to kill cross-presenting CD11b+ cells and completely eliminate the H-2k tumors in most mice. Targeting brain tumor stroma or increasing Ag shedding from tumor cells to enhance cross-presentation may improve the clinical success of T cell adoptive therapies.
Diminished Intracellular Invariant Chain Expression after Vaccinia Virus Infection
Authors: Wang Nan , Weber Ekkehard , Blum Janice S. 
Published: July 2009

Abstract
Vaccinia virus (VV) has been used as a vaccine to eradicate smallpox and as a vaccine for HIV and tumors. However, the immunoevasive properties of VV have raised safety concerns. VV infection of APCs perturbs MHC class II-mediated Ag presentation. Exposure of human B cell lines to VV induced a substantial reduction in cellular expression of the class II chaperone, invariant chain (Ii), during the late stages (i.e., 8–10 h) of infection. Yet, cell viability and surface expression of MHC class II molecules were maintained up to 24 h after exposure to virus. Reductions in Ii and class II mRNA levels were detected as early as 6 h after VV infection of APCs. To examine whether VV was acting solely to disrupt host protein synthesis, B cells were treated with an inhibitor of translation, cycloheximide (CHX). Within 1 h of B cell CHX treatment, Ii protein expression decreased coupled with a loss of class II presentation. Analysis of Ii degradation in VV- or CHX-treated cells, revealed ongoing Ii proteolysis contributing to reduced steady-state Ii levels in these APC. Yet in contrast with CHX, VV infection of APCs altered lysosomal protease expression and Ii degradation. Virus infection induced cellular cathepsin L expression while reducing the levels of other lysosomal proteases. These results demonstrate that at late stages of VV infection, reductions in cellular Ii levels coupled with changes in lysosomal protease activity, contribute in part to defects in class II presentation.
IL-6 Is Required for Airway Mucus Production Induced by Inhaled Fungal Allergens
Authors: Neveu Wendy A. , Allard Jenna B. , Dienz Oliver , Wargo Matthew J. , Ciliberto Gennaro , Whittaker Laurie A. , Rincon Mercedes 
Published: July 2009

Abstract
Allergic asthma is caused by inhaled allergens and is characterized by airway eosinophilia, as well as mucus hypersecretion, which can lead to airflow obstruction. Despite the association of increased IL-6 levels with human atopic asthma, the contribution of IL-6 to the development of allergic airway inflammation triggered by inhaled allergens remains unclear. In this study, we examined the role of IL-6 in a mouse model of allergic airway inflammation induced by direct airway exposure to extracts of Aspergillus fumigatus, a common allergen in humans. We show that inhaled A. fumigatus extracts rapidly trigger the production of IL-6 in the airways. IL-6 appears to be dispensable for the recruitment of eosinophils to the lung during the development of allergic airway inflammation. However, IL-6 is essential for mucus hypersecretion by airway epithelial cells triggered in response to inhaled A. fumigatus Ags. Impaired mucus production caused by IL-6 deficiency correlates with a severe reduction in the levels of IL-13, a major inducer of mucin glycoproteins. Thus, IL-6 is a key regulator of specific hallmark features of allergic airway inflammation and it could be a potential target for pulmonary diseases that are associated with goblet cell metaplasia and mucus hypersecretion.
An Atopy-Associated Polymorphism in the Ectodomain of the IL-4Rα Chain (V50) Regulates the Persistence of STAT6 Phosphorylation
Authors: Ford Andrew Q. , Heller Nicola M. , Stephenson Linda , Boothby Mark R. , Keegan Achsah D. 
Published: July 2009

Abstract
Several commonly occurring polymorphisms in the IL-4Rα have been associated with atopy in humans; the Q576R and the S503P polymorphisms reside in the cytoplasmic domain, whereas the I50 to V50 polymorphism resides in the extracellular domain of the IL-4Rα. The effects of these polymorphisms on signaling remain controversial. To determine the effect of the polymorphisms on IL-4 signaling in human cells, we stably transfected the human monocytic cell line U937 with murine IL-4Rα cDNA bearing the I or V at position 50 and the P503/R576 double mutant. Each form of the murine IL-4Rα mediated tyrosine phosphorylation of STAT6 in response to murine IL-4 treatment similar to the induction of tyrosine phosphorylation by human IL-4 signaling through the endogenous human IL-4Rα. After IL-4 removal, tyrosine-phosphorylated STAT6 rapidly decayed in cells expressing I50 or P503R576 murine IL-4Rα. In contrast, STAT6 remained significantly phosphorylated for several hours after murine IL-4 withdrawal in cells expressing the V50 polymorphism. This persistence in tyrosine-phosphorylated STAT6 was associated with persistence in CIS mRNA expression. Blocking IL-4 signaling during the decay phase using the JAK inhibitor AG490 or the anti-IL-4Rα Ab M1 abrogated the persistence of phosphorylated STAT6 observed in the V50-IL-4Rα-expressing cells. These results indicate that the V50 polymorphism promotes sustained STAT6 phosphorylation and that this process is mediated by continued engagement of IL-4Rα, suggesting enhanced responses of V50 IL-4R when IL-4 is limiting.
IFN Regulatory Factor 4 Regulates the Expression of a Subset of Th2 Cytokines
Authors: Ahyi Ayele-Nati N. , Chang Hua-Chen , Dent Alexander L. , Nutt Stephen L. , Kaplan Mark H. 
Published: July 2009

Abstract
Th2 cells can be subdivided into subpopulations depending on the level of a cytokine and the subsets of cytokines they produce. We have recently identified the ETS family transcription factor PU.1 as regulating heterogeneity in Th2 populations. To define additional factors that might contribute to Th2 heterogeneity, we examined the PU.1 interacting protein IFN-regulatory factor (IRF)4. When Th2 cells are separated based on levels of IL-10 secretion, IRF4 expression segregates into the subset of Th2 cells expressing high levels of IL-10. Infection of total Th2 cells, and IL-10 nonsecreting cells, with retrovirus-expressing IRF4, resulted in increased IL-4 and IL-10 expression, no change in IL-5 or IL-13 production and decreased Il9 transcription. Transfection of an IRF4-specific small interfering RNA into Th2 cells decreases IL-10 production. IRF4 directly binds the Il10 gene as evidenced by chromatin immunoprecipitation assay, and regulates Il10 control elements in a reporter assay. IRF4 interacts with PU.1, and in PU.1-deficient T cells there was an increase in IRF4 binding to the Il10 gene, and in the ability of IRF4 to induce IL-10 production compared with wild-type cells and Il10 promoter activity in a reporter assay. Further heterogeneity of IRF4 expression was observed in Th2 cells analyzed for expression of multiple Th2 cytokines. Thus, IRF4 promotes the expression of a subset of Th2 cytokines and contributes to Th2 heterogeneity.
Palmitoylation-Dependent Plasma Membrane Transport but Lipid Raft-Independent Signaling by Linker for Activation of T Cells
Authors: Hundt Matthias , Harada Yohsuke , De Giorgio Lauren , Tanimura Natsuko , Zhang Weiguo , Altman Amnon 
Published: July 2009

Abstract
Linker for activation of T cells (LAT) is a dually palmitoylated transmembrane adaptor protein essential for T cell development and activation. However, whether LAT palmitoylation and/or lipid raft localization are required for its function is controversial. To address this question, we used a combination of biochemical, imaging, and genetic approaches, including LAT retrovirus-transduced mouse T cells and bone marrow chimeric mice. A nonpalmitoylated, non-lipid raft-residing mutant of transmembrane LAT could not reconstitute T cell development in bone marrow chimeric mice. This mutant was absent from the plasma membrane (PM) and was restricted mainly to the Golgi apparatus. A chimeric, nonpalmitoylated LAT protein consisting of the PM-targeting N-terminal sequence of Src kinase and the LAT cytoplasmic domain (Src-LAT) localized as a peripheral membrane protein in the PM, but outside lipid rafts. Nevertheless, Src-LAT restored T cell development and activation. Lastly, monopalmitoylation of LAT on Cys26 (but not Cys29) was required and sufficient for its PM transport and function. Thus, the function of LAT in T cells requires its PM, but not raft, localization, even when expressed as a peripheral membrane protein. Furthermore, LAT palmitoylation functions primarily as a sorting signal required for its PM transport.