tbuckley/cabot-search huggingface dataset:
Screening for Asymptomatic Bacteriuria in Adults: Evidence for the U.S. Preventive Services Task Force Reaffirmation Recommendation Statement
Authors: Kenneth Lin, Kevin Fajardo
Journal: Annals of Internal Medicine (2008)

Background: Asymptomatic bacteriuria is common, and screening for this condition in pregnant women is a well-established, evidence-based standard of current medical practice. Screening other groups of adults has not been shown to improve outcomes. Purpose: To review new and substantial evidence on screening for asymptomatic bacteriuria, to support the work of the U.S. Preventive Services Task Force. Data Sources: English-language studies of adults (age >18 years) indexed in PubMed and the Cochrane Library and published from 1 January 2002 through 30 April 2007. Study Selection: For benefits of screening or treatment for screened populations, systematic reviews; meta-analyses; and randomized, controlled trials were included. For harms of screening, systematic reviews; meta-analyses; randomized, controlled trials; cohort studies; case–control studies; and case series of large multisite databases were included. Two reviewers independently reviewed titles, abstracts, and full articles for inclusion. Data Extraction: Two reviewers extracted data from studies on benefits of screening and treatment (including decreases in the incidence of adverse maternal and fetal outcomes, symptomatic urinary tract infections, hypertension, and renal function decline). Data Synthesis: An updated Cochrane systematic review of 14 randomized, controlled trials of treatment supports screening for asymptomatic bacteriuria in pregnant women. A randomized, controlled trial and a prospective cohort study show that screening nonpregnant women with diabetes for asymptomatic bacteriuria is unlikely to produce benefits. No new evidence on screening men for asymptomatic bacteriuria or on harms of screening was found. Limitation: The focused search strategy may have missed some smaller studies on the benefits and harms of screening for asymptomatic bacteriuria. Conclusion: The available evidence continues to support screening for asymptomatic bacteriuria in pregnant women, but not in other groups of adults.
Prediction equations for normal and low lung function from the Health Survey for England
Authors: E. Falaschetti, J. Laiho, P. Primatesta, S. Purdon
Journal: European Respiratory Journal (2004)

The aim of this study was to derive new spirometric reference equations for the English population, using the 1995/1996 Health Survey for England, a large nationally representative cross-sectional study. The measurements used were the forced expiratory volume in one second (FEV 1 ) and forced vital capacity (FVC) of a sample of 6,053 “healthy” (nonsmokers with no reported diagnosis of asthma or respiratory symptoms) White people aged ≥16 yrs. Multiple regression analysis, with age and height as predictors, was carried out to estimate prediction equations for mean FEV 1 , FVC and FEV 1 /FVC, separately for males and females. A method based on smoothing multiple estimates of the fifth percentiles of residuals was used to derive prediction equations for the lower limit of normal lung function. The new equations fit the current English adult population considerably better than the European Coal and Steel Community equations, and the proportions of people with “low” (below the fifth percentile) lung function are closer to those expected throughout the whole adult age range (16 to &gt;75 yrs). For the age ranges the studies share in common, the new equations give estimates close to those derived from other nonlinear equations in recent studies. It is, therefore, suggested that these newly developed prediction equations be used for the White English population in both epidemiological studies and clinical practice.
Bronchoscopic Lung Volume Reduction Using Tissue Engineering Principles
Authors: Edward P. Ingenito, Robert L. Berger, A. Cortney Henderson, John J. Reilly, Larry Tsai, Andrew Hoffman
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Bronchoscopic lung volume reduction (BLVR), a minimally invasive procedure based on tissue engineering principles, was performed in six sheep with papain-induced experimental emphysema (EMPH). Physiologic measurements, at baseline, after generation of EMPH, and at 3 and 9 weeks after BLVR, included lung volumes, diffusing capacity (DL(CO)), pressure-volume relationships for the lung and chest wall, pleural pressures generated during active respiratory muscle contraction, lung resistance and dynamic elastance. The animal model displayed hyperinflation (change in total lung capacity +8%; change in residual volume +66%), reduced DL(CO) (-21%), and elevated airway resistance (+76%) that resembled advanced human EMPH. BLVR was well tolerated without complications, and it reduced lung volumes (change in total lung capacity -16%; change in residual volume -55%) in a pattern that resulted in significant improvements in vital capacity (10%). At autopsy, well-organized, peripheral scars associated with tissue contraction were observed at 33 of the 36 (91%) treated sites. There was no evidence of infection, abscess, or granuloma formation, or allergic reaction. Scar tissue, generated by BLVR, replaced hyperinflated lung, reduced overall lung volume, and improved respiratory function safely and consistently. The BLVR technology employed in this study addresses the limitations identified in our prior attempt at BLVR therapy and appears safe and effective enough to justify a trial in humans.
Cooperative Antitumor Effect of Multitargeted Kinase Inhibitor ZD6474 and Ionizing Radiation in Glioblastoma
Authors: Vincenzo Damiano, Davide Melisi, Cataldo Bianco, David Raben, Rosa Caputo, Gabriella Fontanini, Roberto Bianco, Anderson Ryan, A. Raffaele Bianco, Sabino De Placido, Fortunato Ciardiello, Giampaolo Tortora
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Glioblastoma multiforme is an aggressive disease in which vascular endothelial growth factor (VEGF) and the EGF receptor (EGFR) are implicated in tumor growth, relapse, and resistance to radiotherapy and chemotherapy. The VEGF receptors VEGFR-1 (flt-1) and VEGFR-2 (KDR), typically present on endothelial cells, have also been identified in human glioblastoma tissues and cell lines. In addition, EGFR is dysregulated in the majority of human glioblastomas and EGFR overexpression correlates with shorter survival. We have investigated the antitumor and antiangiogenic effect of ZD6474, an inhibitor of both VEGFR and EGFR signaling as a single agent and in combination with ionizing radiation. Experimental Design: We have used ZD6474 and/or ionizing radiation in human glioblastoma cell lines D54 and U251 in vitro and in nude mice bearing established xenografts. The effects of treatment on tumor blood vessels and protein expression were evaluated by Western blot and immunohistochemistry. Results: As single agents, ionizing radiation and ZD6474 caused a dose-dependent inhibition of soft agar growth in D54 and U251 cell lines, whereas a cooperative effect was obtained in combination. Treatment of mice bearing D54 xenografts with either ZD6474 or radiotherapy alone caused tumor growth inhibition that was reversible upon treatment cessation. A cooperative and long-lasting inhibition of tumor growth was obtained with ZD6474 in combination with concomitant radiotherapy. The antiproliferative effect was accompanied by inhibition of VEGF protein expression and inhibition of angiogenesis as measured by vessel counting. Conclusion: This study shows the antitumor activity of ZD6474 in combination with ionizing radiation in glioblastoma both in vitro and in vivo, and provides a scientific rationale to evaluate ZD6474 alone or in combination with radiotherapy in patients affected by this disease.
BRG1/SMARCA4 Inactivation Promotes Non–Small Cell Lung Cancer Aggressiveness by Altering Chromatin Organization
Authors: Tess Orvis, Austin Hepperla, Vonn Walter, Shujie Song, Jeremy Simon, Joel Parker, Matthew D. Wilkerson, Nisarg Desai, Michael B. Major, D. Neil Hayes, Ian J. Davis, Bernard Weissman
Journal: Cancer Research (2014)

Abstract SWI/SNF chromatin remodeling complexes regulate critical cellular processes, including cell-cycle control, programmed cell death, differentiation, genomic instability, and DNA repair. Inactivation of this class of chromatin remodeling complex has been associated with a variety of malignancies, including lung, ovarian, renal, liver, and pediatric cancers. In particular, approximately 10% of primary human lung non–small cell lung cancers (NSCLC) display attenuations in the BRG1 ATPase, a core factor in SWI/SNF complexes. To evaluate the role of BRG1 attenuation in NSCLC development, we examined the effect of BRG1 silencing in primary and established human NSCLC cells. BRG1 loss altered cellular morphology and increased tumorigenic potential. Gene expression analyses showed reduced expression of genes known to be associated with progression of human NSCLC. We demonstrated that BRG1 losses in NSCLC cells were associated with variations in chromatin structure, including differences in nucleosome positioning and occupancy surrounding transcriptional start sites of disease-relevant genes. Our results offer direct evidence that BRG1 attenuation contributes to NSCLC aggressiveness by altering nucleosome positioning at a wide range of genes, including key cancer-associated genes. Cancer Res; 74(22); 6486–98. ©2014 AACR.
P11 The Role Of Gabab Receptor Mechanisms In The Human Cough Reflex
Authors: H. Badri, C. Gibbard, D. Valdramidou, B. Canning, L. Houghton, A. Holt, G. Wilkinson, J. Smith
Journal: Thorax (2014)

<h3>Background</h3> Chronic cough represents an important unmet clinical need. Gamma-aminobutyric acid is a major inhibitory neurotransmitter in the central nervous system (CNS). GABA<sub>B</sub> receptors have been identified peripherally, as well as centrally. Studies in guinea-pigs, have suggested that the activation of GABA<sub>B</sub> receptors in the CNS and PNS can inhibit cough. The only clinically available GABA<sub>B</sub> agonist is Baclofen, and although it has been shown to suppress cough in animals and humans, it causes drowsiness as it is centrally acting. Lesogaberan, is a novel, predominantly peripherally acting GABA<sub>B</sub> agonist. <h3>Objective</h3> To determine whether both peripherally acting (Lesogaberan) and centrally acting (Baclofen) GABA<sub>B</sub> agonists modulate cough responses to inhaled capsaicin compared with placebo in healthy volunteers. <h3>Methods</h3> Single centre, double-blind, double-dummy, three-way crossover trial in healthy controls of Lesogaberan (120 mg MR), Baclofen (40 mg) and placebo. Subjects were treated with single doses of each study medication with a washout period of ≥7 days between doses. Cough responses to inhaled capsaicin were assessed using a novel challenge protocol (1) measured at screening and 2 hrs post dosing (tmax) on each study day. The primary end point was the maximum number of coughs evoked at any concentration of capsaicin (Emax). The secondary end point was the concentration of capsaicin evoking 50% of the maximal response (ED50). <h3>Results</h3> There were 15 patients enrolled onto the study with a median age of 29 years old (IQR25–44); 7 female; mean BMI was 24.6 (±3.0). Lesogaberan treatment was associated with a small, statistically significant increase in Emax (mean 13.4 coughs, 95% CI 10.1–17.9) compared with placebo (11.8, 95% CI 8.8–15.9) (p = 0.04), but had no effect on ED50 (geometric mean 47.4 µM 95% CI 24.4–91.7 vs Placebo 37.6 95% CI 19.2–73.5 p = 0.37), see Figure 1. In contrast, Baclofen had no significant effect on Emax (11.1, CI8.1–15.4) (p = 0.23), but, ED50 was significantly increased compared with placebo (geometric mean 75.2 µM 95% CI 37.2–151.8 p = 0.002). <h3>Conclusion</h3> This data suggests the anti-tussive actions of GABA<sub>B</sub> agonists, against capsaicin-induced cough in healthy volunteers, occurs in the central rather than the peripheral nervous system. <h3>References</h3> <i>Allergy Clin Immunol</i>. 2013 Oct;132(4):847–55
Clinical Implications of Electrocardiographic Left Ventricular Strain and Hypertrophy in Asymptomatic Patients With Aortic Stenosis
Authors: Anders M. Greve, Kurt Boman, Christa Gohlke-Baerwolf, Y. Antero Kesäniemi, Christoph Nienaber, Simon Ray, Kenneth Egstrup, Anne B. Rossebø, Richard B. Devereux, Lars Køber, Ronnie Willenheimer, Kristian Wachtell
Journal: Circulation (2011)

Background— The prognostic impact of ECG left ventricular strain and left ventricular hypertrophy (LVH) in asymptomatic aortic stenosis is not well described. Methods and Results— Data were obtained in asymptomatic patients randomized to simvastatin/ezetimibe combination versus placebo in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Primary end point was the first of myocardial infarction, nonhemorrhagic stroke, heart failure, aortic valve replacement, or cardiovascular death. The predictive value of ECG left ventricular strain (defined as T-wave inversion in leads V 4 through V 6 ) and LVH, assessed by Sokolow-Lyon voltage criteria (R V5–6 +S V1 ≥35 mV) and Cornell voltage-duration criteria {[RaVL+S V3 +(6 mV in women)]×QRS duration ≥2440 mV · ms}, was evaluated by adjustment for other prognostic covariates. A total of 1533 patients were followed for 4.3±0.8 years (6592 patient-years of follow-up), and 627 cardiovascular events occurred. ECG strain was present in 340 patients (23.6%), with LVH by Sokolow-Lyon voltage in 260 (17.1%) and by Cornell voltage-duration product in 220 (14.6%). In multivariable analyses, ECG left ventricular strain was associated with 3.1-fold higher risk of in-study myocardial infarction (95% confidence interval, 1.4–6.8; P =0.004). Similarly, ECG LVH by both criteria predicted, compared with no ECG LVH, 5.8-fold higher risk of heart failure (95% confidence interval, 2.0–16.8), 2.0-fold higher risk of aortic valve replacement (95% confidence interval, 1.3–3.1; both P =0.001), and 2.5-fold higher risk of a combined end point of myocardial infarction, heart failure, or cardiovascular death (95% confidence interval, 1.3–4.9; P =0.008). Conclusions— ECG left ventricular strain and LVH were independently predictive of poor prognosis in patients with asymptomatic aortic stenosis. Clinical Trial Registration— http://www.clinicaltrials.gov . Unique identifier: NCT00092677.
β-Catenin Functions Mainly as an Adhesion Molecule in Patients with Squamous Cell Cancer of the Head and Neck
Authors: Ziwei Yu, Paul M. Weinberger, Elayne Provost, Bruce G. Haffty, Clarence Sasaki, J. Joe, R.L. Camp, D.L. Rimm, Amanda Psyrri
Journal: Clinical Cancer Research (2005)

Abstract Background: β-catenin, depending on subcellular localization, plays a dual role in carcinogenesis: as a signaling factor (in the nucleus) and as an adhesion molecule (in cell membrane). In this study, we sought to determine the role of β-catenin in head and neck carcinogenesis. Methods: First, we studied the incidence of mutations of β-catenin in a cohort of 60 head and neck squamous cell cancers (HNSCC). We subsequently evaluated the protein expression levels of β-catenin in a cohort of oropharyngeal squamous cell cancer tissue microarray using a novel in situ method of quantitative protein analysis and correlated those with cyclin D1 levels and clinical and pathologic data. Results: The mean follow-up time for survivors was 45 months and for all patients was 35 months. We found no mutations in the cohort of 60 HNSCC. β-catenin displayed primarily membranous expression pattern. Patients with high tumor-node-metastasis stage were more likely to have high expression of β-catenin (P = 0.040). Patients with low β-catenin expression had a local recurrence rate of 79% compared with 29% for patients with high β-catenin tumors (P = 0.0021). Univariate Cox regression revealed a hazard ratio for low β-catenin tumors of 3.6 (P = 0.004). Kaplan-Meier analysis showed that patients with low β-catenin expressing tumors trended toward worse 5-year disease-free survival (P = 0.06). In multivariate analysis, only β-catenin expression status was an independent prognostic factor (P = 0.044) for local recurrence. Tumors with high β-catenin had low cyclin D1 and vice versa (P = 0.007). Conclusions: The absence of activating β-catenin mutations combined with the inverse correlation between β-catenin levels with cyclin D1 levels and outcome suggest that β-catenin mainly functions as an adhesion and not signaling molecule in HNSCC.
Advances in the management of endometriosis: an update for clinicians
Authors: PierGiorgio Crosignani, David Olive, Agneta Bergqvist, Anthony Luciano
Journal: Human Reproduction Update (2005)

Endometriosis is a chronic and recurrent disease characterized by the presence and proliferation of endometrial tissue outside the uterine cavity, which occurs in approximately 10% of women of reproductive age. In this estrogen-dependent disorder, lesions become inactive and gradually undergo regression during states of ovarian down-regulation, such as amenorrhoea or menopause. The impact of endometriosis includes impaired fertility potential, as well as symptoms of dysmenorrhoea, dyspareunia and chronic non-menstrual pain, all of which adversely affect quality of life. Management of endometriosis focuses on pain relief and includes medical and surgical treatment. Pharmacologic therapies currently in use include combination oral contraceptives (COCs), danazol, GnRH analogues and progestins. Although some agents show efficacy in relieving pain, all differ in their side effects, making it difficult to achieve a balance between efficacy and safety. Efficacy has been demonstrated with danazol or GnRH analogues; however, treatment is limited to 6 months because of significant metabolic side effects. Alternatives for longer-term management of symptoms include add-back therapy with GnRH analogues, COCs or progestins. Newer options for treatment of endometriosis include depot medroxyprogesterone acetate subcutaneous injection, as well as several agents under investigation that may prove to have therapeutic potential.
Randomised Controlled Trial Comparing Laparoscopic and Robot-assisted Radical Prostatectomy
Authors: Francesco Porpiglia, Ivano Morra, Marco Lucci Chiarissi, Matteo Manfredi, Fabrizio Mele, Susanna Grande, Francesca Ragni, Massimiliano Poggio, Cristian Fiori
Journal: European Urology (2012)
ELECTROENCEPHALOGRAPHIC ANALYSES OF BEHAVIOR PROBLEM CHILDREN
Authors: Herbert H. Jasper, Philip Solomon, Charles Bradley
Journal: American Journal of Psychiatry (1938)

Electroencephalographic and clinical studies of 71 behavior problem children have been presented. Abnormalities in brain potentials were found in 71 per cent of this group with very marked abnormalities appearing in 59 per cent. Epileptiform electrical activity was observed in 39 per cent of the cases. These latter patients showed characteristic mental and emotional disturbances analogous to those often associated with the epileptic personality. In only two of these cases was epilepsy suspected previous to the electroencephalographic findings and none were having convulsions at the time of examination. It is concluded that abnormal brain function as revealed by the electroencephalogram is an important component in the aetiological picture of the majority of a group of problem children whose disorder had been considered as primarily psychogenic previous to using this method of diagnosis. The nature of the fundamental pathology of the brain indicated is not as yet known, but the findings have been found important in evaluating prognosis and treatment.
Fast-food hyper-alimentation and exercise restriction in healthy subjects
Authors: R D Johnston, G P Aithal, S D Ryder, I A MacDonald
Journal: Gut (2009)

We read with great interest the recent article by Kechegias et al on the hepatic effects of fast-food hyper-alimentation and exercise restriction ( Gut 2008; 57 :649–54). The metabolic effects of fast-food consumption are a major public health issue, and have recently resulted in demands for the energy and nutrient content labelling of fast-food menus.1 Fast-food consumers significantly underestimate the energy and fat content of fast-foodstuffs, and their consumptive behaviours alter when they are informed of the foodstuffs’ true content.2

We would first like to commend them on performing such a valuable study. We agree with their conclusion that a dietary, as well as an alcohol history is an imperative component of the evaluation of patients with an idiopathically elevated alanine aminotransferase (ALT). Our …
Predictors of In-Hospital Mortality in Patients With Acute Ischemic Stroke Treated With Thrombolytic Therapy
Authors: Peter U. Heuschmann
Journal: JAMA (2004)

Data are limited regarding the risks and benefits of thrombolytic therapy for acute ischemic stroke outside of clinical trials.To investigate predictors of in-hospital mortality in patients with ischemic stroke treated with intravenous tissue plasminogen activator (tPA) within a pooled analysis of large German stroke registers.Prospective, observational cohort study conducted at 225 community and academic hospitals throughout Germany cooperating within the German Stroke Registers Study Group.A total of 1658 patients with acute ischemic stroke who were admitted to study hospitals between 2000 and 2002 and were treated with tPA.In-hospital mortality.One hundred sixty-six patients (10%) who received tPA died during hospitalization, with 67.5% of these deaths occurring within 7 days. Factors predicting in-hospital death after tPA use were older age (for each 10-year increment in age, adjusted odds ratio [OR], 1.6; 95% confidence interval [CI], 1.3-1.9) and altered level of consciousness (adjusted OR, 3.4; 95% CI, 2.4-4.7). The overall rate of symptomatic intracranial hemorrhage was 7.1% and increased with age. One or more serious complications was observed in 27.2% of all patients and in 83.9% of patients who died after tPA treatment. An inverse relation between the number of patients treated with tPA in the respective hospital and the risk of in-hospital death was observed (adjusted OR, 0.97; 95% CI, 0.96-0.99 for each additional patient treated with tPA per year).In patients with ischemic stroke who are treated with tPA, disturbances of consciousness and increasing age are associated with increased in-hospital mortality.