tbuckley/cabot-search huggingface dataset:
Oral Steroids for Acute Radiculopathy Due to a Herniated Lumbar Disk
Authors: Harley Goldberg, William Firtch, Mark Tyburski, Alice Pressman, Lynn Ackerson, Luisa Hamilton, Wayne Smith, Ryan Carver, Annu Maratukulam, Lawrence A. Won, Eugene Carragee, Andrew L. Avins
Journal: JAMA (2015)

IMPORTANCEOral steroids are commonly used to treat acute sciatica due to a herniated disk but have not been evaluated in an appropriately powered clinical trial.OBJECTIVE To determine if oral prednisone is more effective than placebo in improving function and pain among patients with acute sciatica.DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, placebo-controlled clinical trial conducted from 2008 to 2013 in a large integrated health care delivery system in Northern California.Adults (n=269) with radicular pain for 3 months or less, an Oswestry Disability Index (ODI) score of 30 or higher (range, 0-100; higher scores indicate greater dysfunction), and a herniated disk confirmed by magnetic resonance imaging were eligible.INTERVENTIONS Participants were randomly assigned in a 2:1 ratio to receive a tapering 15-day course of oral prednisone (5 days each of 60 mg, 40 mg, and 20 mg; total cumulative dose = 600 mg; n = 181) or matching placebo (n = 88). MAIN OUTCOMES AND MEASURESThe primary outcome was ODI change at 3 weeks; secondary outcomes were ODI change at 1 year, change in lower extremity pain (measured on a 0-10 scale; higher scores indicate more pain), spine surgery, and Short Form 36 Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) scores (0-100 scale; higher scores better).RESULTS Observed baseline and 3-week mean ODI scores were 51.2 and 32.2 for the prednisone group and 51.1 and 37.5 for the placebo group, respectively.The prednisone-treated group showed an adjusted mean 6.4-point (95% CI, 1.9-10.9;P = .006)greater improvement in ODI scores at 3 weeks than the placebo group and a mean 7.4-point (95% CI, 2.2-12.5;P = .005)greater improvement at 52 weeks.Compared with the placebo group, the prednisone group showed an adjusted mean 0.3-point (95% CI, -0.4 to 1.0; P = .34)greater reduction in pain at 3 weeks and a mean 0.6-point (95% CI, -0.2 to 1.3; P = .15)greater reduction at 52 weeks.The prednisone group showed an adjusted mean 3.3-point (95% CI, 1.3-5.2;P = .001)greater improvement in the SF-36 PCS score at 3 weeks, no difference in the SF-36 PCS score at 52 weeks (mean, 2.5; 95% CI, -0.3 to 5.4; P = .08),no change in the SF-36 MCS score at 3 weeks (mean, 2.2; 95% CI, -0.4 to 4.8; P = .10),and an adjusted 3.6-point (95% CI, 0.6-6.7;P = .02)greater improvement in the SF-36 MCS score at 52 weeks.There were no differences in surgery rates at 52-week follow-up.Having 1 or more adverse events at 3-week follow-up was more common in the prednisone group than in the placebo group (49.2% vs 23.9%; P < .001).CONCLUSIONS AND RELEVANCE Among patients with acute radiculopathy due to a herniated lumbar disk, a short course of oral steroids, compared with placebo, resulted in modestly improved function and no improvement in pain.
Molecular characterisation of an hepatitis C virus outbreak in an hospital emergency setting
Authors: J.C. Saiz, M. Bruguera, M. Giménez-Barcons, S. Franco, F. Puig-Basagoiti, J.M. Sánchez-Tapias, S. Fabregas, R. Vega, N. Camps, A. Dominguez, L. Salleras
Journal: Journal of Hepatology (2001)
Induction of peripheral tolerance to class I major histocompatibility complex (MHC) alloantigens in adult mice: transfused class I MHC-incompatible splenocytes veto clonal responses of antigen-reactive Lyt-2+ T cells.
Authors: K Heeg, H Wagner
Journal: The Journal of Experimental Medicine (1990)

The efficacy and the mode of action of pretransplant transfusion with class I major histocompatibility complex (MHC)-disparate splenocytes in establishing a state of peripheral tolerance in adult mice is analyzed. Adult mice injected intravenously with a critical number of approximately 5 x 10(7) allogenic splenocytes accept skin grafts and develop chimerism in the peripheral lymphatic tissues, but not in thymus and bone marrow. In parallel, a split tolerance evolves: the frequency of class I MHC-reactive Lyt-2+ cytotoxic T lymphocyte precursor (CTL-p)- and interleukin 2 (IL-2)-producing T cells falls off in the peripheral lymphoid tissue, but remains unaltered intrathymically. In particular, high affinity CTL-p become clonally undetectable. In vivo generation of tolerant cells is cyclosporin A resistant, but dependent on recipient L3T4+ T cells. Loss of Lyt-2+ CTL-p- and IL-2-producing T cell precursors is not due to active suppression, but is caused by clonal anergy. Donor-derived chimeric cells positively selected 7 d after intravenous transfusion exhibit in vitro the hallmarks of veto cells, i.e., paralyze CTL-p reactive to donor-type class I MHC alloantigens. We conclude that the peripheral (split) tolerance induced in vivo by pretransplant transfusion operates because donor-type cells develop in vivo efficiently into "veto cells," which in turn induce a state of clonal anergy within antigen-reactive Lyt-2+ T lymphocytes.
Use of a Clinical Model for Safe Management of Patients with Suspected Pulmonary Embolism
Authors: P S Wells, J S Ginsberg, D R Anderson, C Kearon, M Gent, A G Turpie, J Bormanis, J Weitz, M Chamberlain, D Bowie, D Barnes, J Hirsh
Journal: Annals of Internal Medicine (1998)

Background: The low specificity of ventilation-perfusion lung scanning complicates the management of patients with suspected pulmonary embolism. Objective: To determine the safety of a clinical model for patients with suspected pulmonary embolism. Design: Prospective cohort study. Setting: Five tertiary care hospitals. Patients: 1239 inpatients and outpatients with suspected pulmonary embolism. Interventions: A clinical model categorized pretest probability of pulmonary embolism as low, moderate, or high, and ventilation-perfusion scanning and bilateral deep venous ultrasonography were done. Testing by serial ultrasonography, venography, or angiography depended on pretest probability and lung scans. Measurements: Patients were considered positive for pulmonary embolism if they had an abnormal pulmonary angiogram, abnormal ultrasonogram or venogram, high-probability ventilation-perfusion scan plus moderate or high pretest probability, or venous thromboembolic event during the 3-month follow-up. All other patients were considered negative for pulmonary embolism. Rates of pulmonary embolism during follow-up in patients who had a normal lung scan and those with a non-high-probability scan and normal serial ultrasonogram were compared. Results: Pretest probability was low in 734 patients (3.4% with pulmonary embolism), moderate in 403 (27.8% with pulmonary embolism), and high in 102 (78.4% with pulmonary embolism). Three of the 665 patients (0.5% [95% CI, 0.1% to 1.3%]) with low or moderate pretest probability and a non-high-probability scan who were considered negative for pulmonary embolism had pulmonary embolism or deep venous thrombosis during 90-day follow-up; this rate did not differ from that in patients with a normal scan (0.6% [CI, 0.1% to 1.8%]; P > 0.2). Conclusion: Management of patients with suspected pulmonary embolism on the basis of pretest probability and results of ventilation-perfusion scanning is safe.
Calcium Phosphate Crystals Induce Cell Death in Human Vascular Smooth Muscle Cells
Authors: Alexandra E. Ewence, Martin Bootman, H. Llewelyn Roderick, Jeremy N. Skepper, Geraldine McCarthy, Matthias Epple, Markus Neumann, Catherine M. Shanahan, Diane Proudfoot
Journal: Circulation Research (2008)

Vascular calcification is associated with an increased risk of myocardial infarction; however, the mechanisms linking these 2 processes are unknown. Studies in macrophages have suggested that calcium phosphate crystals induce the release of proinflammatory cytokines; however, no studies have been performed on the effects of calcium phosphate crystals on vascular smooth muscle cell function. In the present study, we found that calcium phosphate crystals induced cell death in human aortic vascular smooth muscle cells with their potency depending on their size and composition. Calcium phosphate crystals of approximately 1 μm or less in diameter caused rapid rises in intracellular calcium concentration, an effect that was inhibited by the lysosomal proton pump inhibitor, bafilomycin A1. Bafilomycin A1 also blocked vascular smooth muscle cell death suggesting that crystal dissolution in lysosomes leads to an increase in intracellular calcium levels and subsequent cell death. These studies give novel insights into the bioactivity of calcified deposits and suggest that small calcium phosphate crystals could destabilize atherosclerotic plaques by initiating inflammation and by causing vascular smooth muscle cell death.
Endogenous Sex Hormones, Breast Cancer Risk, and Tamoxifen Response: An Ancillary Study in the NSABP Breast Cancer Prevention Trial (P-1)
Authors: Mary S. Beattie, Joseph P. Costantino, Steven R. Cummings, D. Lawrence Wickerham, Victor G. Vogel, Mitch Dowsett, Elizabeth J. Folkerd, Walter C. Willett, Norman Wolmark, Susan E. Hankinson
Journal: JNCI Journal of the National Cancer Institute (2006)

Background : Prospective studies have shown an association between increased serum levels of estradiol and testosterone and breast cancer risk in postmenopausal women. Raloxifene has been shown to reduce breast cancer risk more in women with high estradiol levels than in those with lower levels. The purpose of this study was to determine whether sex hormone levels were associated with breast cancer risk and with response to tamoxifen in a high-risk population. Methods: Using a case–cohort design, we studied 135 women with postmenopausal breast cancer and 275 postmenopausal women without breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project Cancer Prevention Trial (P-1) and who had been treated with tamoxifen or placebo for 69 months. We measured estradiol, testosterone, and sex hormone–binding globulin by using radioimmunoassay in baseline plasma samples. Relative risks (RRs) and 95% confidence intervals (CIs) for invasive breast cancer were estimated for each quartile of sex hormone level using Cox proportional hazards models. All statistical tests were two-sided. Results : Median plasma levels of estradiol, testosterone, and sex hormone–binding globulin were similar between the case and cohort groups. The relative risk of breast cancer for women in the placebo group was not associated with sex hormone levels (risk of estrogen receptor–positive breast cancer in women by quartile of estradiol: Q1 [lowest], RR = 1.0; Q2, RR = 1.16, 95% CI = 0.49 to 2.7; Q3, RR = 1.08, 95% CI = 0.45 to 2.61; and Q4, RR = 1.29, 95% CI = 0.59 to 2.82). The reduced risk of invasive breast cancer in tamoxifen-treated women compared with placebo-treated women was not associated with sex hormone levels. Conclusions: These data do not support the use of endogenous sex hormone levels to identify women who are at particularly high risk of breast cancer and who are most likely to benefit from chemoprevention with tamoxifen.
Stopping Randomized Trials Early for Benefit and Estimation of Treatment Effects&lt;subtitle&gt;Systematic Review and Meta-regression Analysis&lt;/subtitle&gt;
Authors: Dirk Bassler, Matthias Briel, Victor M Montori, Melanie Lane, Paul Glasziou, Qi Zhou, Diane Heels-Ansdell, Stephen D Walter, Gordon H Guyatt, David N Flynn, Mohamed B Elamin, Mohammad Hassan Murad, Nisrin O Abu Elnour, Julianna F Lampropulos, Amit Sood, Rebecca J Mullan, Patricia J Erwin, Clare R Bankhead, Rafael Perera, Carolina Ruiz Culebro, John J You, Sohail M Mulla, Jagdeep Kaur, Kara A Nerenberg, Holger Schünemann, Deborah J Cook, Kristina Lutz, Christine M Ribic, Noah Vale, German Malaga, Elie A Akl, Ignacio Ferreira-Gonzalez, Pablo Alonso-Coello, Gerard Urrutia, Regina Kunz, Heiner C Bucher, Alain J Nordmann, Heike Raatz, Suzana Alves da Silva, Fabio Tuche, Brigitte Strahm, Benjamin Djulbegovic, Neill K J Adhikari, Edward J Mills, Femida Gwadry-Sridhar, Haresh Kirpalani, Heloisa P Soares, Paul J Karanicolas, Karen E A Burns, Per Olav Vandvik, Fernando Coto-Yglesias, Pedro Paulo M Chrispim, Tim Ramsay
Journal: JAMA (2010)

Theory and simulation suggest that randomized controlled trials (RCTs) stopped early for benefit (truncated RCTs) systematically overestimate treatment effects for the outcome that precipitated early stopping.To compare the treatment effect from truncated RCTs with that from meta-analyses of RCTs addressing the same question but not stopped early (nontruncated RCTs) and to explore factors associated with overestimates of effect.Search of MEDLINE, EMBASE, Current Contents, and full-text journal content databases to identify truncated RCTs up to January 2007; search of MEDLINE, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews of Effects to identify systematic reviews from which individual RCTs were extracted up to January 2008.Selected studies were RCTs reported as having stopped early for benefit and matching nontruncated RCTs from systematic reviews. Independent reviewers with medical content expertise, working blinded to trial results, judged the eligibility of the nontruncated RCTs based on their similarity to the truncated RCTs.Reviewers with methodological expertise conducted data extraction independently.The analysis included 91 truncated RCTs asking 63 different questions and 424 matching nontruncated RCTs. The pooled ratio of relative risks in truncated RCTs vs matching nontruncated RCTs was 0.71 (95% confidence interval, 0.65-0.77). This difference was independent of the presence of a statistical stopping rule and the methodological quality of the studies as assessed by allocation concealment and blinding. Large differences in treatment effect size between truncated and nontruncated RCTs (ratio of relative risks <0.75) occurred with truncated RCTs having fewer than 500 events. In 39 of the 63 questions (62%), the pooled effects of the nontruncated RCTs failed to demonstrate significant benefit.Truncated RCTs were associated with greater effect sizes than RCTs not stopped early. This difference was independent of the presence of statistical stopping rules and was greatest in smaller studies.
MicroRNA-221 Targets Bmf in Hepatocellular Carcinoma and Correlates with Tumor Multifocality
Authors: Laura Gramantieri, Francesca Fornari, Manuela Ferracin, Angelo Veronese, Silvia Sabbioni, George Adrian Calin, Gian Luca Grazi, Carlo Maria Croce, Luigi Bolondi, Massimo Negrini
Journal: Clinical Cancer Research (2009)

Abstract Deregulated cell proliferation and apoptosis play a major role in hepatocellular carcinoma (HCC). MicroRNAs participate in the modulation of key molecules linked to hepatocarcinogenesis. Purpose: This study aims to investigate the role of miR-221 in the modulation of Bmf, a proapoptotic BH3-only protein, and to characterize miR-221 contribution to hepatocarcinogenesis through modulation of apoptosis. Experimental Design: Transfection of miR-221 and anti-miR-221 in HCC-derived cell lines and luciferase reporter assay were used to assess Bmf as a target of miR-221. Modulation of miR-221 and Bmf expression contributed to characterize their role in anoikis. Primary HCC tissues were analyzed to assess the clinical relevance of in vitro findings. Results: Enforced miR-221 expression caused Bmf down-regulation, whereas anti-miR-221 induced its up-regulation. A luciferase reporter assay confirmed Bmf as a target of miR-221. Following matrix detachment, miR-221 silencing led to increased apoptotic cell death. The analysis of HCC tissues revealed an inverse correlation between miR-221 and Bmf expression and a direct correlation between Bmf and activated caspase-3, as a marker of apoptosis. High miR-221 levels were associated with tumor multifocality and reduced time to recurrence after surgery. Conclusions: Our results indicate that miR-221, by targeting Bmf, inhibits apoptosis. Moreover, in HCC, miR-221 overexpression is associated with a more aggressive phenotype. These findings, together with the previously reported modulation of CDKN1B/p27 and CDKN1C/p57, show that miR-221 simultaneously affects multiple pro-oncogenic pathways and suggest miR-221 as a potential target for nonconventional treatment against HCC. (Clin Cancer Res 2009;15(16):5073–81)
HIV As a Risk Factor for Lung Cancer in Women: Data From the Women's Interagency HIV Study
Authors: Alexandra M. Levine, Eric C. Seaberg, Nancy A. Hessol, Susan Preston-Martin, Sylvia Silver, Mardge H. Cohen, Kathryn Anastos, Howard Minkoff, Jan Orenstein, Geraldina Dominguez, D. Heather Watts
Journal: Journal of Clinical Oncology (2010)

Prior reports of an increased risk of lung cancer in HIV-infected individuals have not always included control groups, nor considered other risk factors such as tobacco exposure. We sought to determine the role of HIV infection and highly active antiretroviral therapy (HAART) on lung cancer incidence in 2,651 HIV-infected and 898 HIV-uninfected women from the Women's Interagency HIV Study (WIHS).A prospective study of the incidence rates of lung cancer was conducted, with cases identified through medical records, death certificates, and state cancer registries. Standardized incidence ratios (SIRs) were calculated to compare lung cancer incidence among HIV-infected and uninfected WIHS participants, with population-based expectations using the Surveillance, Epidemiology, and End Results registry. Behavioral characteristics in the WIHS were compared to US women by age and race adjusting the population-based data from the National Health and Nutritional Examination Survey (NHANES) III.Incidence rates of lung cancer were similar among HIV-infected and uninfected WIHS women. Lung cancer SIRs were increased in both HIV-infected and -uninfected women compared with population expectations, but did not differ by HIV status. Among HIV-infected women, lung cancer incidence rates were similar in pre-HAART and HAART eras. All WIHS women with lung cancer were smokers; the risk of lung cancer increased with cumulative tobacco exposure. WIHS women were statistically more likely to smoke than US women studied in NHANES III.HIV infection is strongly associated with smoking behaviors that increase lung cancer risk. The role of HIV itself remains to be clarified.
Gene expression atlas of the mouse central nervous system: impact and interactions of age, energy intake and gender
Authors: Xiangru Xu, Ming Zhan, Wenzhen Duan, Vinayakumar Prabhu, Randall Brenneman, William Wood, Jeff Firman, Huai Li, Peisu Zhang, Carol Ibe, Alan B Zonderman, Dan L Longo, Suresh Poosala, Kevin G Becker, Mark P Mattson
Journal: Genome biology (2007)

Abstract Background The structural and functional complexity of the mammalian central nervous system (CNS) is organized and modified by complicated molecular signaling processes that are poorly understood. Results We measured transcripts of 16,896 genes in 5 CNS regions from cohorts of young, middle-aged and old male and female mice that had been maintained on either a control diet or a low energy diet known to retard aging. Each CNS region (cerebral cortex, hippocampus, striatum, cerebellum and spinal cord) possessed its own unique transcriptome fingerprint that was independent of age, gender and energy intake. Less than 10% of genes were significantly affected by age, diet or gender, with most of these changes occurring between middle and old age. The transcriptome of the spinal cord was the most responsive to age, diet and gender, while the striatal transcriptome was the least responsive. Gender and energy restriction had particularly robust influences on the hippocampal transcriptome of middle-aged mice. Prominent functional groups of age- and energy-sensitive genes were those encoding proteins involved in DNA damage responses (Werner and telomere-associated proteins), mitochondrial and proteasome functions, cell fate determination (Wnt and Notch signaling) and synaptic vesicle trafficking. Conclusion Mouse CNS transcriptomes responded to age, energy intake and gender in a regionally distinctive manner. The systematic transcriptome dataset also provides a window into mechanisms of age-, diet- and sex-related CNS plasticity and vulnerability.
Coronary artery fistula: report of three cases.
Authors: D Wheatley, E N Coleman, J M Reid
Journal: Thorax (1975)

Three children are described with a right coronary artery fistula communicating with a right heart chamber. Each had a continuous murmur like that of a patent ductus arteriosus but situated at a lower level. Aortography established the diagnosis and excluded any accompanying malformation. It is concluded that to prevent complications surgical treatment should be recommended.
Chop deletion reduces oxidative stress, improves β cell function, and promotes cell survival in multiple mouse models of diabetes
Authors: Benbo Song, Donalyn Scheuner, David Ron, Subramaniam Pennathur, Randal J. Kaufman
Journal: Journal of Clinical Investigation (2008)

The progression from insulin resistance to type 2 diabetes is caused by the failure of pancreatic beta cells to produce sufficient levels of insulin to meet the metabolic demand. Recent studies indicate that nutrient fluctuations and insulin resistance increase proinsulin synthesis in beta cells beyond the capacity for folding of nascent polypeptides within the endoplasmic reticulum (ER) lumen, thereby disrupting ER homeostasis and triggering the unfolded protein response (UPR). Chronic ER stress promotes apoptosis, at least in part through the UPR-induced transcription factor C/EBP homologous protein (CHOP). We assessed the effect of Chop deletion in multiple mouse models of type 2 diabetes and found that Chop-/- mice had improved glycemic control and expanded beta cell mass in all conditions analyzed. In both genetic and diet-induced models of insulin resistance, CHOP deficiency improved beta cell ultrastructure and promoted cell survival. In addition, we found that isolated islets from Chop-/- mice displayed increased expression of UPR and oxidative stress response genes and reduced levels of oxidative damage. These findings suggest that CHOP is a fundamental factor that links protein misfolding in the ER to oxidative stress and apoptosis in beta cells under conditions of increased insulin demand.