bluuebunny/crossref_metadata_2025_split huggingface dataset:
Magnetic Resonance Imaging of the Throwing Elbow in the Uninjured, High School–Aged Baseball Pitcher
Authors: Hurd Wendy J. , Eby Sarah , Kaufman Kenton R. , Murthy Naveen S. 
Published: January 2011

Background: Tissue adaptations in response to pitching are an expected finding during magnetic resonance imaging (MRI) evaluation of the throwing elbow of adult pitchers. These changes are considered normal in the absence of symptom complaints. It is unclear when during the playing career these tissue adaptations are initiated. Hypothesis: Abnormalities in the appearance of the throwing elbow compared with the nonthrowing elbow would be visible during MRI assessment of this asymptomatic population of high school–aged throwers. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Twenty-three uninjured, asymptomatic male high school–aged baseball pitchers (mean age, 16 years) with no history of elbow injury were recruited for the study. Participants had a minimum of 3 years’ experience with pitching as their primary position (mean experience, 6 years). Bilateral elbow MRI examinations were performed using a standardized protocol including fast spin-echo proton-density (axial and coronal), T1-weighted (sagittal), and T2-weighted fat-saturated (axial, sagittal, and coronal) sequences. Osteoarticular, ligamentous, musculotendinous, and neural structures were evaluated and compared bilaterally. The images were reviewed by a musculoskeletal radiologist who was blinded to all the gathered data on these athletes, including limb dominance. Results: Three participants (13%) had no abnormalities. Fifteen individuals (65%) had asymmetrical anterior band ulnar collateral ligament thickening, including 4 individuals who also had mild sublime tubercle/anteromedial facet edema. Fourteen participants (61%) had posteromedial subchondral sclerosis of the ulnotrochlear articulation, including 8 (35%) with a posteromedial ulnotrochlear osteophyte, and 4 (17%) with mild posteromedial ulnotrochlear chondromalacia. Ten individuals (43%) had multiple abnormal findings in the throwing elbow. Conclusion: Thickening of the anterior band of the ulnar collateral ligament and posteromedial subchondral sclerosis of the trochlea are common findings in the high school–aged pitcher and may be considered normal clinical findings in the absence of symptom complaints. Other changes in tissue appearance of the throwing elbow are uncommon in this age group and should be regarded with a higher level of caution when evaluating for the presence of injury. An understanding of the MRI appearance of the uninjured youth pitcher is necessary for clinicians to distinguish between normal adaptations and the presence of injury.
Low molecular weight heparin administration in cancer patients with hypercoagulability-related complications and carrying brain metastases: A case series study
Authors: Vitale Felice Vito , Rotondo Stefano , Sessa Edoardo , Parisi Alessandra , Giaimo Valentina , D’Angelo Alessandro , Antonelli Giovanna , Romeo Placido , Ferraù Francesco 
Published: January 2011

Background. Venous thromboembolism (VTE) and brain metastases (MTS) are significant clinical problems in the cancer patient population. Brain MTS and deep vein thrombosis are life-threatening conditions because of the risk of fatal endocranic hypertension and pulmonary embolism. Low molecular weight heparin (LMWH) is a major treatment for cancer patients suffering from VTE with regard to the management of the acute phase and subsequent secondary prophylaxis. Treatment with anticoagulants is feared because of the risk of triggering a massive intracranial hemorrhage. Methods. The medical records of patients with hypercoagulability-related complications and carrying brain MTS treated with LMWH, in a 10-year period, were scrutinized. The authors aimed to focus on the occurrence of intracranial hemorrhage in anticoagulated patients; furthermore, data were collected with regard to the characteristics of the administered LMWHs along with the duration and dosing of the anticoagulative treatment. Results. A total of 38 patients (pts) carrying an intracranial metastatic tumor were administered LMWHs: calcium nadroparin (32 pts); enoxaparin (2 pts); reviparin (2 pts); parnaparin (2 pts). Reason for LMWH therapy: deep vein thrombosis and/or pulmonary embolism (15 pts); superficial thrombophlebitis (15 pts); intracardiac thrombus (1 pt); mild DIC (5 pts); acute DIC (1 pt); Raynaud phenomenon (1 pt); atrial fibrillation (1 pt). Median duration of LMWH therapy: 13 weeks (range 1–52). None of the patients developed clinical and/or radiographic findings imputable to intracranial hemorrhage. Conclusion. There is no standard medical approach for the management of patients who require anticoagulant treatment and are suffering from brain MTS. These patients as necessary, might be anticoagulated with LMWH and its dose reduction is to be considered.
A Swedish national post-marketing surveillance study of natalizumab treatment in multiple sclerosis
Authors: Holmén Carolina , Piehl Fredrik , Hillert Jan , Fogdell-Hahn Anna , Lundkvist Malin , Karlberg Elin , Nilsson Petra , Dahle Charlotte , Feltelius Nils , Svenningsson Anders , Lycke Jan , Olsson Tomas 
Published: January 2011

Background: A post marketing surveillance study was conducted to evaluate safety and efficacy of natalizumab in Swedish multiple sclerosis (MS) patients since its introduction in August 2006 until March 2010. Methods: Patients were registered in the web-based Swedish MS-registry at 40 locations and evaluated every 6 months. Adverse events and clinical outcomes were recorded. Results: One thousand one hundred and fifty-two patients were included (71.4% female) and 149 patients stopped treatment; the main reason was planned pregnancy. Anti-natalizumab antibodies were found in 4.5% (52 patients) of which 1.6% displayed persistent antibodies. Serious adverse events were rare, but included three cases with progressive multifocal leukoencephalopathy (PML). There were seven fatal cases, probably unrelated to the natalizumab treatment. For relapsing–remitting MS patients ( n = 901), mean Expanded Disability Status Scale (EDSS, −10.7%), Multiple Sclerosis Severity Scale (MSSS, −20.4%), Multiple Sclerosis Impact Scale (MSIS-29, physical −9.9%, psychological −13.3%) and Symbol Digit Modalities Test (SDMT, +10.7%) all showed significant improvements during 24 months of treatment with natalizumab. The Swedish web-based MS quality registry proved to function as a platform for post-marketing MS drug surveillance, providing long-term data regarding drug effects and adverse events beyond clinical trials. Conclusions: Our results indicate that natalizumab is generally well tolerated and has sustained efficacy for patients with active MS, though the risk of PML is still an important concern.
Matrix-Associated and Autologous Chondrocyte Transplantation in the Ankle
Authors: Nehrer Stefan , Domayer S.E. , Hirschfeld Clemens , Stelzeneder David , Trattnig Siegfried , Dorotka Ronald 
Published: January 2011

Background: New matrix-associated autologous chondrocyte transplantation (MACT) techniques may facilitate the treatment of chondral defects in talar cartilage and provide good clinical outcome in the long term. The aim of this prospective case series was to monitor the clinical outcome after autologous chondrocyte transplantation (ACT) and MACT in the ankle to gain data on the mid-term efficacy of the procedure. Methods: Seventeen cases of talar cartilage defects were assessed with the American Orthopaedic Foot and Ankle Score (AOFAS), a modified Cincinnati score, and a subjective ankle-hindfoot score (AHS) at a mean of 61 (24-135) months after surgery. Nine patients consented to an additional magnetic resonance imaging (MRI) exam, including T2 mapping at 3T. ACT was carried out with a periosteal flap (4 cases) or with a matrix-assisted ACT technique (Hyalograft C; 13 cases). Results: Significant improvement was found in all cases. The AOFAS improved from 50.0 to 87.3, the AHS from 43.8 to 84.1, and the modified Cincinnati score from 2.9 to 6.9. MRI data demonstrated good defect filling, and T2 mapping results indicated that the collagen and water content of the repair tissue was comparable to adjacent cartilage. Discussion: MACT and ACT in the ankle can provide good and excellent long-term outcome and resulted in repair tissue with T2 properties similar to native cartilage in the majority of cases. Matrix-assisted implantation with the hyaluronan matrix allows for a less invasive surgical procedure. Level of evidence: 4; prospective case series study.
Defective nonhomologous end joining blocks B-cell development in FLT3/ITD mice
Authors: Li Li , Zhang Li , Fan Jinshui , Greenberg Kathleen , Desiderio Stephen , Rassool Feyruz V. , Small Donald 
Published: January 2011

AbstractWe have generated an FLT3/ITD knock-in mouse model in which mice with an FLT3/ITD mutation develop myeloproliferative disease (MPD) and a block in early B-lymphocyte development. To elucidate the role of FLT3/ITD signaling in B-cell development, we studied VDJ recombination in the pro-B cells of FLT3/ITD mice and discovered an increased frequency of DNA double strand breaks (DSBs) introduced by the VDJ recombinase. Early pro-B cells from FLT3/ITD mice were found to have a lower efficiency and decreased accuracy of DSB repair by nonhomologous end joining (NHEJ), which is required for rejoining DSBs during VDJ recombination. Reduced NHEJ repair probably results from reduced expression of Ku86, a key component of the classic DNA-PK-dependent NHEJ pathway. In compensation, early pro-B cells from FLT3/ITD cells mice show increased levels of the alternative, and highly error-prone, NHEJ pathway protein PARP1, explaining the increase in repair errors. These data suggest that, in early pro-B cells from FLT3/ITD mice, impairment of classic NHEJ decreases the ability of cells to complete postcleavage DSB ligation, resulting in failure to complete VDJ recombination and subsequent block of B-lymphocyte maturation. These findings might explain the poor prognosis of leukemia patients with constitutive activation of FLT3 signaling.
Epigenetic modification of the human CCR6 gene is associated with stable CCR6 expression in T cells
Authors: Steinfelder Svenja , Floess Stefan , Engelbert Dirk , Haeringer Barbara , Baron Udo , Rivino Laura , Steckel Bodo , Gruetzkau Andreas , Olek Sven , Geginat Jens , Huehn Jochen , Hamann Alf 
Published: January 2011

AbstractCCR6 is a chemokine receptor expressed on Th17 cells and regulatory T cells that is induced by T-cell priming with certain cytokines, but how its expression and stability are regulated at the molecular level is largely unknown. Here, we identified and characterized a noncoding region of the human CCR6 locus that displayed unmethylated CpG motifs (differentially methylated region [DMR]) selectively in CCR6+ lymphocytes. CCR6 expression on circulating CD4+ T cells was stable on cytokine-induced proliferation but partially down-regulated on T-cell receptor stimulation. However, CCR6 down-regulation was mostly transient, and the DMR within the CCR6 locus remained demethylated. Notably, in vitro induction of CCR6 expression with cytokines in T-cell receptor-activated naive CD4+ T cells was not associated with a demethylated DMR and resulted in unstable CCR6 expression. Conversely, treatment with the DNA methylation inhibitor 5′-azacytidine induced demethylation of the DMR and led to increased and stable CCR6 expression. Finally, when cloned into a reporter gene plasmid, the DMR displayed transcriptional activity in memory T cells that was suppressed by DNA methylation. In summary, we have identified a noncoding region of the human CCR6 gene with methylation-sensitive transcriptional activity in CCR6+ T cells that controls stable CCR6 expression via epigenetic mechanisms.
IRF8 and IRF3 cooperatively regulate rapid interferon-β induction in human blood monocytes
Authors: Li Peng , Wong Joyce Jing-Yi , Sum Calvin , Sin Wei-Xiang , Ng Kok-Quan , Koh Mickey B. C. , Chin Keh-Chuang 
Published: January 2011

AbstractRobust and rapid induction of interferon-β (IFN-β) in monocytes after pathogenic stimulation is a hallmark of innate immune responses. Here, we reveal the molecular mechanism underlying this key property that is exclusive to human blood monocytes. We found that IFN-β was produced rapidly in primary human monocytes as a result of cooperation between the myeloid-specific transcription factor IRF8 and the ubiquitous transcription factor IRF3. Knockdown of IRF8 in monocytes abrogated IFN-β transcription, whereas reintroduction of IRF8 into the IRF8−/− 32Dcl3 murine myeloid cell line reinstated IFN-β transcription. Moreover, we provide evidence that IRF8 constitutively binds to the ETS/IRF composite element of the IFN-β promoter region together with PU.1 in vivo. Furthermore we uncovered a requirement for IRF3, a master regulator of IFN-β production, as a previously un-indentified interaction partner of IRF8. We mapped the protein-protein interacting regions of IRF3 and IRF8, and found that their interaction was independent of the DNA-binding domain and the IRF association domain of IRF8 and IRF3, respectively. Therefore, we propose a model for the rapid induction of IFN-β in monocytes, whereby IRF8 and PU.1 form a scaffold complex on the IFN-β promoter to facilitate the recruitment of IRF3, thus enabling rapid IFN-β transcription.
Complete response correlates with long-term progression-free and overall survival in elderly myeloma treated with novel agents: analysis of 1175 patients
Authors: Gay Francesca , Larocca Alessandra , Wijermans Pierre , Cavallo Federica , Rossi Davide , Schaafsma Ron , Genuardi Mariella , Romano Alessandra , Liberati Anna Marina , Siniscalchi Agostina , Petrucci Maria T. , Nozzoli Chiara , Patriarca Francesca , Offidani Massimo , Ria Roberto , Omedè Paola , Bruno Benedetto , Passera Roberto , Musto Pellegrino , Boccadoro Mario , Sonneveld Pieter , Palumbo Antonio 
Published: January 2011

AbstractComplete response (CR) was an uncommon event in elderly myeloma patients until novel agents were combined with standard oral melphalan-prednisone. This analysis assesses the impact of treatment response on progression-free survival (PFS) and overall survival (OS). We retrospectively analyzed 1175 newly diagnosed myeloma patients, enrolled in 3 multicenter trials, treated with melphalan-prednisone alone (n = 332), melphalan-prednisone-thalidomide (n = 332), melphalan-prednisone-bortezomib (n = 257), or melphalan-prednisone-bortezomib-thalidomide (n = 254). After a median follow-up of 29 months, the 3-year PFS and OS were 67% and 27% (hazard ratio = 0.16; P < .001), and 91% and 70% (hazard ratio = 0.15; P < .001) in patients who obtained CR and in those who achieved very good partial response, respectively. Similar results were observed in patients older than 75 years. Multivariate analysis confirmed that the achievement of CR was an independent predictor of longer PFS and OS, regardless of age, International Staging System stage, and treatment. These findings highlight a significant association between the achievement of CR and long-term outcome, and support the use of novel agents to achieve maximal response in elderly patients, including those more than 75 years. This trial was registered at www.clinicaltrials.gov as #NCT00232934, #ISRCTN 90692740, and #NCT01063179.
B-cell depletion reactivates B lymphopoiesis in the BM and rejuvenates the B lineage in aging
Authors: Keren Zohar , Naor Shulamit , Nussbaum Shahar , Golan Karin , Itkin Tomer , Sasaki Yoshiteru , Schmidt-Supprian Marc , Lapidot Tsvee , Melamed Doron 
Published: January 2011

AbstractAging is associated with a decline in B-lymphopoiesis in the bone marrow and accumulation of long-lived B cells in the periphery. These changes decrease the body's ability to mount protective antibody responses. We show here that age-related changes in the B lineage are mediated by the accumulating long-lived B cells. Thus, depletion of B cells in old mice was followed by expansion of multipotent primitive progenitors and common lymphoid progenitors, a revival of B-lymphopoiesis in the bone marrow, and generation of a rejuvenated peripheral compartment that enhanced the animal's immune responsiveness to antigenic stimulation. Collectively, our results suggest that immunosenescence in the B-lineage is not irreversible and that depletion of the long-lived B cells in old mice rejuvenates the B-lineage and enhances immune competence.
The host genomic environment of the provirus determines the abundance of HTLV-1–infected T-cell clones
Authors: Gillet Nicolas A. , Malani Nirav , Melamed Anat , Gormley Niall , Carter Richard , Bentley David , Berry Charles , Bushman Frederic D. , Taylor Graham P. , Bangham Charles R. M. 
Published: January 2011

AbstractHuman T-lymphotropic virus type 1 (HTLV-1) persists by driving clonal proliferation of infected T lymphocytes. A high proviral load predisposes to HTLV-1–associated diseases. Yet the reasons for the variation within and between persons in the abundance of HTLV-1–infected clones remain unknown. We devised a high-throughput protocol to map the genomic location and quantify the abundance of > 91 000 unique insertion sites of the provirus from 61 HTLV-1+ persons and > 2100 sites from in vitro infection. We show that a typical HTLV-1–infected host carries between 500 and 5000 unique insertion sites. We demonstrate that negative selection dominates during chronic infection, favoring establishment of proviruses integrated in transcriptionally silenced DNA: this selection is significantly stronger in asymptomatic carriers. We define a parameter, the oligoclonality index, to quantify clonality. The high proviral load characteristic of HTLV-1–associated inflammatory disease results from a larger number of unique insertion sites than in asymptomatic carriers and not, as previously thought, from a difference in clonality. The abundance of established HTLV-1 clones is determined by genomic features of the host DNA flanking the provirus. HTLV-1 clonal expansion in vivo is favored by orientation of the provirus in the same sense as the nearest host gene.
Music Recomposed: Remarks on the History of the Same
Authors: Kramer Lawrence 
Published: January 2011

Stanley Cavell's 1967 essay “Music Discomposed” claims that twentieth-century musical modernism incorporates the constant possibility of “fraudulence,” thus provoking the Philistine objection: why can't we write like Mozart any more? For Cavell the question is preeminently a matter of fact: not that no one can write like Mozart any more but that no one does. The question of why remains unanswered.My own essay proposes an answer. On historical grounds it shifts the question from Mozart to Beethoven to focus on a specific composition. When my students listen to Beethoven's “Kreutzer” sonata in connection with Tolstoy's infamous novella of the same name, they readily hear the passion and eroticism that Tolstoy imputed to the music. But the sonata dates from 1803; no one would write it today to evoke fatal attraction. Why should that be so? Must it be, and if so, why again? The answer—inevitably equivocal—is to be found not in the shopworn trope that imparts a sovereign irreversibility to the history of form or style, but in the historicality of subjectivity on one hand and of musical meaning on the other.
The anatomical relationship between the saphenous nerve and the great saphenous vein
Authors: Veverková L , Jedlička V , Vlček P , Kalač J 
Published: January 2011

Objective Damage to the saphenous nerve (SN) has been a known complication during varicose vein surgeries. We tested whether a better knowledge of the anatomy of the SN and the great saphenous vein (GSV) can prevent such damage. Methods We conducted a morphological and histological examination on 86 limbs from 43 cadavers in order to analyse the anatomical interrelation between the SN and the GSV in the lower leg and we also measured the distance between the nerve and the vein in a sample of 42 sections from three parts of the lower leg. Results The anatomical relationship between the SN and the GSV is varied and the two structures run close to each other so a better knowledge of their anatomy in itself proved insufficient in preventing damage to the SN. Conclusion However, in the case of endovenous laser therapy and radiofrequency ablation tumescent anaesthesia decreases the risk of damage to the SN.
Cardio-respiratory and metabolic responses to different levels of compression during submaximal exercise
Authors: Sperlich B , Haegele M , Krüger M , Schiffer T , Holmberg H-C , Mester J 
Published: January 2011

Objective The effects of knee-high socks that applied different levels of compression (0, 10, 20, 30 and 40 mmHg) on various cardio-respiratory and metabolic parameters during submaximal running were analysed. Methods Fifteen well-trained, male endurance athletes (age: 22.2 ± 1.3 years; peak oxygen uptake: 57.2 ± 4.0 mL/minute/kg) performed a ramp test to determine peak oxygen uptake. Thereafter, all athletes carried out five periods of submaximal running (at approximately 70% of peak oxygen uptake) with and without compression socks that applied the different levels of pressure. Cardiac output and index, stroke volume, arterio-venous difference in oxygen saturation, oxygen uptake, arterial oxygen saturation, heart rate and blood lactate were monitored before and during all of these tests. Results Cardiac output ( P = 0.29) and index ( P = 0.27), stroke volume ( P = 0.50), arterio-venous difference in oxygen saturation ( P = 0.11), oxygen uptake ( P = 1.00), arterial oxygen saturation ( P = 1.00), heart rate ( P = 1.00) and arterial lactate concentration ( P = 1.00) were unaffected by compression (effect sizes = 0.00–0.65). Conclusion This first evaluation of the potential effects of increasing levels of compression on cardio-respiratory and metabolic parameters during submaximal exercise revealed no effects whatsoever.
Venous giant post-thrombotic chronic ulcer: successful treatment with Bosentan
Authors: Solís J V , Portero J L , Ribé L 
Published: January 2011

Objective To report a case of a refractory post-thrombotic chronic venous ulcer managed with an off-label treatment. Method We present the case of an 82-year-old woman with a previous medical history of severe hypertension and a deep vein thrombosis three years before. A refractory giant chronic venous ulcer in her left leg was treated with Bosentan. Results The appearance of the ulcer improved in the first 45 days, worsened after an unintended stop of the treatment and was almost resolved after 90 days of treatment. Ulcer-associated pain improved very quickly and so, in only one week, opioid treatment was stopped. Bosentan treatment was well tolerated, with only mild and manageable side effects. Conclusion Treatment with Bosentan has been successful in the treatment of this case of refractory chronic venous ulcer.