tbuckley/cabot-search huggingface dataset:
Outcomes of Small Renal Mass Needle Core Biopsy, Nondiagnostic Percutaneous Biopsy, and the Role of Repeat Biopsy
Authors: Michael J. Leveridge, Antonio Finelli, John R. Kachura, Andrew Evans, Hannah Chung, Daniel A. Shiff, Kimberly Fernandes, Michael A.S. Jewett
Journal: European Urology (2011)
IgG Glycan Hydrolysis Attenuates ANCA-Mediated Glomerulonephritis
Authors: Mirjan M. van Timmeren, Betty S. van der Veen, Coen A. Stegeman, Arjen H. Petersen, Thomas Hellmark, Mattias Collin, Peter Heeringa
Journal: Journal of the American Society of Nephrology (2010)

Anti-neutrophil cytoplasmic autoantibodies (ANCA) directed against myeloperoxidase (MPO) and proteinase 3 (Pr3) are considered pathogenic in ANCA-associated necrotizing and crescentic glomerulonephritis (NCGN) and vasculitis. Modulation of ANCA IgG glycosylation may potentially reduce its pathogenicity by abolishing Fc receptor–mediated activation of leukocytes and complement. Here, we investigated whether IgG hydrolysis by the bacterial enzyme endoglycosidase S (EndoS) attenuates ANCA-mediated NCGN. In vitro, treatment of ANCA IgG with EndoS significantly attenuated ANCA-mediated neutrophil activation without affecting antigen-binding capacity. In a mouse model of anti-MPO IgG/LPS-induced NCGN, we induced disease with either unmodified or EndoS-treated (deglycosylated) anti-MPO IgG. In separate experiments, we administered EndoS systemically after disease induction with unmodified anti-MPO IgG. Pretreatment of anti-MPO IgG with EndoS reduced hematuria, leukocyturia, and albuminuria and attenuated both neutrophil influx and formation of glomerular crescents. After inducing disease with unmodified anti-MPO IgG, systemic treatment with EndoS reduced albuminuria and glomerular crescent formation when initiated after 3 but not 24 hours. In conclusion, IgG glycan hydrolysis by EndoS attenuates ANCA-induced neutrophil activation in vitro and prevents induction of anti-MPO IgG/LPS-mediated NCGN in vivo. Systemic treatment with EndoS early after disease induction attenuates the development of disease. Thus, modulation of IgG glycosylation is a promising strategy to interfere with ANCA-mediated inflammatory processes.
Effect of caffeine supplementation on haematological and biochemical variables in elite soccer players under physical stress conditions * COMMENTARY
Authors: Adriana Bassini-Cameron, Eric Sweet, Altamiro Bottino, Christina Bittar, Carlos Veiga, Luiz-Claudio Cameron
Journal: British Journal of Sports Medicine (2007)

To evaluate the effect of caffeine on white cell distribution and muscle injury markers in professional soccer players during exercise.22 male athletes completed a placebo controlled double blind test protocol to simulate a soccer match, followed by a Yo-Yo intermittent recovery test.Exercise caused an increase in packed cell volume that was enhanced by caffeine. Caffeine and exercise had a synergistic effect on the blood lymphocyte count, which increased by about 38% after exercise, and by an additional 35% when combined with caffeine. Caffeine promoted an exercise independent rise in circulating monocytes, and a synergistic action of exercise and caffeine was observed on segmented neutrophils. Caffeine promoted thrombocytosis. Plasma adenosine deaminase, aspartate aminotransferase, and lactate dehydrogenase concentrations were enhanced by exercise, and alanine transaminase concentration was enhanced in both groups, with a synergistic effect of caffeine.The pronounced increase in the white cell count in the group receiving caffeine appeared to be caused by greater muscle stress and consequently more intense endothelial and muscle cell injury. The use of caffeine may augment the risk of muscle damage in athletes.
Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation in Patients With Acute Myeloid Leukemia
Authors: Boglarka Gyurkocza, Rainer Storb, Barry E. Storer, Thomas R. Chauncey, Thoralf Lange, Judith A. Shizuru, Amelia A. Langston, Michael A. Pulsipher, Christopher N. Bredeson, Richard T. Maziarz, Benedetto Bruno, Finn B. Petersen, Michael B. Maris, Edward Agura, Andrew Yeager, Wolfgang Bethge, Firoozeh Sahebi, Frederick R. Appelbaum, David G. Maloney, Brenda M. Sandmaier
Journal: Journal of Clinical Oncology (2010)

Allogeneic hematopoietic cell transplantation (HCT) after high-dose conditioning regimens imposes prohibitively high risks of morbidity and mortality for patients with high-risk acute myeloid leukemia (AML) who are older or have comorbid conditions. Here, we examined outcomes after nonmyeloablative allogeneic HCT in such patients.Two hundred seventy-four patients (median age, 60 years) with de novo or secondary AML underwent allogeneic HCT from related (n = 118) or unrelated donors (n = 156) after conditioning with 2 Gy of total-body irradiation (TBI) with or without fludarabine. A calcineurin inhibitor and mycophenolate mofetil were used for postgrafting immunosuppression.With a median follow-up of 38 months in surviving patients, the estimated overall survival at 5 years was 33%. The estimated 5-year relapse/progression and nonrelapse mortality rates were 42% and 26%, respectively. The cumulative incidences of grades 2, 3, and 4 acute graft-versus-host disease (GVHD) were 38%, 9%, and 5%, respectively. The cumulative incidence of chronic GVHD at 5 years was 44%. Patients in first and second complete remission had better survival rates than patients with more advanced disease (37% and 34% v 18%, respectively). Patients with HLA-matched related or unrelated donors had similar survivals. Unfavorable cytogenetic risk status was associated with increased relapse and subsequent mortality. Chronic GVHD was associated with lower relapse risk.Allogeneic HCT from related or unrelated donors after conditioning with low-dose TBI and fludarabine, relying almost exclusively on graft-versus-leukemia effects, can result in long-term remissions in older or medically infirm patients with AML.
Door-to-Balloon Time With Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction Impacts Late Cardiac Mortality in High-Risk Patients and Patients Presenting Early After the Onset of Symptoms
Authors: Bruce R. Brodie, Charles Hansen, Thomas D. Stuckey, Scott Richter, Debra S. VerSteeg, Navin Gupta, William E. Downey, Mark Pulsipher
Journal: Journal of the American College of Cardiology (2006)
Randomized Comparison of Minimally Invasive Direct Coronary Artery Bypass Surgery Versus Sirolimus-Eluting Stenting in Isolated Proximal Left Anterior Descending Coronary Artery Stenosis
Authors: Holger Thiele, Patrick Neumann-Schniedewind, Stephan Jacobs, Enno Boudriot, Thomas Walther, Friedrich-Wilhelm Mohr, Gerhard Schuler, Volkmar Falk
Journal: Journal of the American College of Cardiology (2009)
Diffuse Large B-cell Lymphoma Classification Tied Up Nicely with a “String”
Authors: Lisa M. Rimsza
Journal: Clinical Cancer Research (2015)

Molecular classification of diffuse large B-cell lymphoma (DLBCL) is a critical biologic, prognostic, and predictive distinction. Since the discovery of two molecular types of DLBCL in otherwise morphologically indistinguishable cases, numerous methodologies for making this distinction have been published. A method and technical platform may now be reaching consensus.
Adipocyte-hepatocyte crosstalk and the pathogenesis of nonalcoholic fatty liver disease
Authors: Briohny Smith, Jacob George, Kris Kowdley, Geoffrey McCaughan, Christian Trautwein
Journal: Hepatology (2009)

A high-fat diet causes activation of the regulatory protein c-Jun NH2-terminal kinase 1 (JNK1) and triggers development of insulin resistance. JNK1 is therefore a potential target for therapeutic treatment of metabolic syndrome. We explored the mechanism of JNK1 signaling by engineering mice in which the Jnk1 gene was ablated selectively in adipose tissue. JNK1 deficiency in adipose tissue suppressed high-fat diet–induced insulin resistance in the liver. JNK1-dependent secretion of the inflammatory cytokine interleukin-6 by adipose tissue caused increased expression of liver SOCS3, a protein that induces hepatic insulin resistance. Thus, JNK1 activation in adipose tissue can cause insulin resistance in the liver.
BCR/ABL Inhibits Mismatch Repair to Protect from Apoptosis and Induce Point Mutations
Authors: Tomasz Stoklosa, Tomasz Poplawski, Mateusz Koptyra, Margaret Nieborowska-Skorska, Grzegorz Basak, Artur Slupianek, Marina Rayevskaya, Ilona Seferynska, Larry Herrera, Janusz Blasiak, Tomasz Skorski
Journal: Cancer Research (2008)

Abstract BCR/ABL kinase–positive chronic myelogenous leukemia (CML) cells display genomic instability leading to point mutations in various genes including bcr/abl and p53, eventually causing resistance to imatinib and malignant progression of the disease. Mismatch repair (MMR) is responsible for detecting misincorporated nucleotides, resulting in excision repair before point mutations occur and/or induction of apoptosis to avoid propagation of cells carrying excessive DNA lesions. To assess MMR activity in CML, we used an in vivo assay using the plasmid substrate containing enhanced green fluorescent protein (EGFP) gene corrupted by T:G mismatch in the start codon; therefore, MMR restores EGFP expression. The efficacy of MMR was reduced ∼2-fold in BCR/ABL-positive cell lines and CD34+ CML cells compared with normal counterparts. MMR was also challenged by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), which generates O6-methylguanine and O4-methylthymine recognized by MMR system. Impaired MMR activity in leukemia cells was associated with better survival, accumulation of p53 but not of p73, and lack of activation of caspase 3 after MNNG treatment. In contrast, parental cells displayed accumulation of p53, p73, and activation of caspase 3, resulting in cell death. Ouabain-resistance test detecting mutations in the Na+/K+ ATPase was used to investigate the effect of BCR/ABL kinase–mediated inhibition of MMR on mutagenesis. BCR/ABL-positive cells surviving the treatment with MNNG displayed ∼15-fold higher mutation frequency than parental counterparts and predominantly G:C→A:T and A:T→G:C mutator phenotype typical for MNNG-induced unrepaired lesions. In conclusion, these results suggest that BCR/ABL kinase abrogates MMR activity to inhibit apoptosis and induce mutator phenotype. [Cancer Res 2008;68(8):2576–80]
Evaluation of Tumor Response, Disease Control, Progression-Free Survival, and Time to Progression As Potential Surrogate End Points in Metastatic Breast Cancer
Authors: Tomasz Burzykowski, Marc Buyse, Martine J. Piccart-Gebhart, George Sledge, James Carmichael, Hans-Joachim Lück, John R. Mackey, Jean-Marc Nabholtz, Robert Paridaens, Laura Biganzoli, Jacek Jassem, Marijke Bontenbal, Jacques Bonneterre, Stephen Chan, Gul Atalay Basaran, Patrick Therasse
Journal: Journal of Clinical Oncology (2008)

Overall survival (OS) can be observed only after prolonged follow-up, and any potential effect of first-line therapies on OS may be confounded by the effects of subsequent therapy. We investigated whether tumor response, disease control, progression-free survival (PFS), or time to progression (TTP) could be considered a valid surrogate for OS to assess the benefits of first-line therapies for patients with metastatic breast cancer.Individual patient data were collected on 3,953 patients in 11 randomized trials that compared an anthracycline (alone or in combination) with a taxane (alone or in combination with an anthracycline). Surrogacy was assessed through the correlation between the end points as well as through the correlation between the treatment effects on the end points.Tumor response (survival odds ratio [OR], 6.2; 95% CI, 5.3 to 7.0) and disease control (survival OR, 5.5; 95% CI, 4.8 to 6.3) were strongly associated with OS. PFS (rank correlation coefficient, 0.688; 95% CI, 0.686 to 0.690) and TTP (rank correlation coefficient, 0.682; 95% CI, 0.680 to 0.684) were moderately associated with OS. Response log ORs were strongly correlated with PFS log hazard ratios (linear coefficient [rho], 0.96; 95% CI, 0.73 to 1.19). Response and disease control log ORs and PFS and TTP log hazard ratios were poorly correlated with log hazard ratios for OS, but the confidence limits of rho were too wide to be informative.No end point could be demonstrated as a good surrogate for OS in these trials. Tumor response may be an acceptable surrogate for PFS.
Congenital secretory diarrhoea caused by activating germline mutations in<i>GUCY2C</i>
Authors: Thomas Müller, Insha Rasool, Peter Heinz-Erian, Eva Mildenberger, Christian Hülstrunk, Andreas Müller, Laurent Michaud, Bart G P Koot, Antje Ballauff, Julia Vodopiutz, Stefan Rosipal, Britt-Sabina Petersen, Andre Franke, Irene Fuchs, Heiko Witt, Heinz Zoller, Andreas R Janecke, Sandhya S Visweswariah
Journal: Gut (2015)

Congenital sodium diarrhoea (CSD) refers to a form of secretory diarrhoea with intrauterine onset and high faecal losses of sodium without congenital malformations. The molecular basis for CSD remains unknown. We clinically characterised a cohort of infants with CSD and set out to identify disease-causing mutations by genome-wide genetic testing.We performed whole-exome sequencing and chromosomal microarray analyses in 4 unrelated patients, followed by confirmatory Sanger sequencing of the likely disease-causing mutations in patients and in their family members, followed by functional studies.We identified novel de novo missense mutations in GUCY2C, the gene encoding receptor guanylate cyclase C (GC-C) in 4 patients with CSD. One patient developed severe, early-onset IBD and chronic arthritis at 4 years of age. GC-C is an intestinal brush border membrane-bound guanylate cyclase, which functions as receptor for guanylin, uroguanylin and Escherichia coli heat-stable enterotoxin. Mutations in GUCY2C were present in different intracellular domains of GC-C, and were activating mutations that enhanced intracellular cyclic guanosine monophosphate accumulation in a ligand-independent and ligand-stimulated manner, following heterologous expression in HEK293T cells.Dominant gain-of-function GUCY2C mutations lead to elevated intracellular cyclic guanosine monophosphate levels and could explain the chronic diarrhoea as a result of decreased intestinal sodium and water absorption and increased chloride secretion. Thus, mutations in GUCY2C indicate a role for this receptor in the pathogenesis of sporadic CSD.
Terlipressin inhibits<i>in vivo</i>aortic iNOS expression induced by lipopolysaccharide in rats with biliary cirrhosis
Authors: Richard Moreau, Eric Barrière, Khalid A. Tazi, Bernard Lardeux, Delphine Dargère, Waldemar Urbanowicz, Odile Poirel, Laurence Chauvelot-Moachon, Marie-Christine Guimont, Dominique Bernuau, Didier Lebrec
Journal: Hepatology (2002)

In cirrhosis, lipopolysaccharide (LPS, a product of Gram-negative bacteria) in the blood may cause septic shock. LPS-elicited induction of arterial inducible nitric oxide synthase (iNOS) results in nitric oxide (NO)-induced vasodilation, which causes arterial hypotension and hyporeactivity to α 1 -adrenergic constrictors. In vitro studies have suggested that vasopressin inhibits iNOS expression in cultured vascular smooth muscle cells exposed to LPS. Thus, the aim of this study was to investigate the effects of terlipressin administration (a vasopressin analog) on in vivo LPS-induced aortic iNOS in rats with cirrhosis. LPS (1 mg/kg, intravenously) was administered followed by the intravenous administration of terlipressin (0.05 mg/kg, intravenously) or placebo 1 hour later. Arterial pressure was measured, and contractions to phenylephrine (an α 1 -adrenoceptor agonist), iNOS activity, and iNOS expressions (mRNA and protein) were investigated in isolated aortas. LPS-induced arterial hypotension and aortic hyporeactivity to phenylephrine were abolished in rats that received terlipressin. LPS-induced aortic iNOS activity and expression were suppressed in terlipressin-treated rats. In conclusion, in LPS-challenged rats with cirrhosis, terlipressin administration inhibits in vivo LPS-induced aortic iNOS expression. Terlipressin administration may be a novel approach for the treatment of arterial hypotension and hyporeactivity to α 1 -adrenergic constrictors in patients with cirrhosis and septic shock.
Lung Cancer, Cardiopulmonary Mortality, and Long-term Exposure to Fine Particulate Air Pollution
Authors: C Arden Pope, Richard T Burnett, Michael J Thun, Eugenia E Calle, Daniel Krewski, Kazuhiko Ito, George D Thurston
Journal: JAMA (2002)

ContextAssociations have been found between day-to-day particulate air pollution and increased risk of various adverse health outcomes, including cardiopulmonary mortality. However, studies of health effects of long-term particulate air pollution have been less conclusive.ObjectiveTo assess the relationship between long-term exposure to fine particulate air pollution and all-cause, lung cancer, and cardiopulmonary mortality.Design, Setting, and ParticipantsVital status and cause of death data were collected by the American Cancer Society as part of the Cancer Prevention II study, an ongoing prospective mortality study, which enrolled approximately 1.2 million adults in 1982. Participants completed a questionnaire detailing individual risk factor data (age, sex, race, weight, height, smoking history, education, marital status, diet, alcohol consumption, and occupational exposures). The risk factor data for approximately 500 000 adults were linked with air pollution data for metropolitan areas throughout the United States and combined with vital status and cause of death data through December 31, 1998.Main Outcome MeasureAll-cause, lung cancer, and cardiopulmonary mortality.ResultsFine particulate and sulfur oxide–related pollution were associated with all-cause, lung cancer, and cardiopulmonary mortality. Each 10-µg/m3 elevation in fine particulate air pollution was associated with approximately a 4%, 6%, and 8% increased risk of all-cause, cardiopulmonary, and lung cancer mortality, respectively. Measures of coarse particle fraction and total suspended particles were not consistently associated with mortality.ConclusionLong-term exposure to combustion-related fine particulate air pollution is an important environmental risk factor for cardiopulmonary and lung cancer mortality.
Impact of Language Barriers on Complications and Mortality Among Immigrants With Diabetes: A Population-Based Cohort Study
Authors: Karen Okrainec, Gillian L. Booth, Simon Hollands, Chaim M. Bell
Journal: Diabetes Care (2014)

OBJECTIVE Our objective was to examine the effect of language barriers on the risk of acute and chronic complications of diabetes and on mortality among immigrants. RESEARCH DESIGN AND METHODS Linked health and immigration databases were used to identify 87,707 adults with diabetes who immigrated to Ontario, Canada, between 1985 and 2005. These individuals were included in our cohort and stratified by language ability at the time of their immigration application. Primary end points included: one or more emergency department visit or hospitalization for 1) hypo- or hyperglycemia, skin and soft tissue infection, or foot ulcer and 2) a cardiovascular event or death between April 1, 2005, and February 29, 2012. RESULTS Our cohort was followed up for a median of 6.9 person-years. Immigrants with language barriers were older (mean age, 49 ± 15 vs. 42 ± 13 years; P &amp;lt; 0.001), more likely to have immigrated for family reunification (66% vs. 38%, P &amp;lt; 0.001), had less education (secondary school or less and no education, 82% vs. 53%; P &amp;lt; 0.001), and a higher use of health care (mean visits, 8.6 ± 12.1 vs. 7.8 ± 11.2; P &amp;lt; 0.001). Immigrants with language barriers were not found to have higher adjusted rates of diabetes complications (acute complications: hazard ratio [HR] 0.99, 95% CI 0.93–1.05; cardiovascular events or death: HR 0.95, 95% CI 0.91–0.99). Significant predictors included older age, being unmarried, living in a rural neighborhood, and having less education. Immigrants who were older (≥65 years) and who had arrived through family reunification had a lower risk of cardiovascular events or death (HR 0.88, 95% CI 0.81–0.96). CONCLUSIONS In a heterogenous immigrant population with universal insurance, language barriers were not found to increase the risk of diabetes complications. However, their effect may vary based on age at time of landing, education level, marital status, and neighborhood of settlement.
Public Health, GIS, and Spatial Analytic Tools
Authors: Gerard Rushton
Journal: Annual Review of Public Health (2003)

▪ Abstract We review literature that uses spatial analytic tools in contexts where Geographic Information Systems (GIS) is the organizing system for health data or where the methods discussed will likely be incorporated in GIS-based analyses in the future. We conclude the review with the point of view that this literature is moving toward the development and use of systems of analysis that integrate the information geo-coding and data base functions of GISystems with the geo-information processing functions of GIScience. The rapidity of this projected development will depend on the perceived needs of the public health community for spatial analysis methods to provide decision support. Recent advances in the analysis of disease maps have been influenced by and benefited from the adoption of new practices for georeferencing health data and new ways of linking such data geographically to potential sources of environmental exposures, the locations of health resources and the geodemographic characteristics of populations. This review focuses on these advances.
Prevalence of spondyloarthropathies in France: 2001
Authors: A Saraux
Journal: Annals of the Rheumatic Diseases (2005)

To estimate the prevalence of spondyloarthropathies (SpAs) in France in a multiregional representative sample in the year 2001.A two stage random sample was constituted in seven areas from the national telephone directory and the next birthday method in each household. Interviewers were patient-members of self help groups trained to administer telephone surveys using a validated questionnaire for detecting inflammatory joint disease. Quality of data collection was controlled periodically. SpA was confirmed by the patient's rheumatologist or by clinical examination. Prevalence estimates after probability sampling correction were standardised for age and sex (1999 national census).Among the 15 219 anonymous telephone numbers selected, 3.6% were places of work or secondary residences and were excluded. The phone interview participation rate ranged across regions from 55.1 to 69.9%. 3554 men and 5841 women were included in the study. Twenty nine cases of SpA were confirmed. All but one fulfilled ESSG criteria. Mean age was 47 years (range 21-78). The overall prevalence standardised for age and sex was 0.30% (95% confidence interval (CI) 0.17 to 0.46). Prevalence was similar in women (0.29% (95% CI 0.14 to 0.49)) and men (0.31 % (95% CI 0.12 to 0.60)). Geographical analysis by department clustering found no significant differences. The prevalence of SpA was as high as that of rheumatoid arthritis.Prevalence of SpA in France was 0.30% in 2001, with no difference between women and men. Ankylosing spondylitis and psoriatic arthritis were the most common SpA subsets.