tbuckley/cabot-search huggingface dataset:
The metabolic syndrome is amplified in hypothyroid rheumatoid arthritis patients: a cross-sectional study
Authors: H G Raterman, I C van Eijk, A E Voskuyl, M J L Peters, B A C Dijkmans, V P van Halm, S Simsek, W F Lems, M T Nurmohamed
Journal: Annals of the Rheumatic Diseases (2008)

Rheumatoid arthritis (RA) patients are at increased risk of cardiovascular disease (CVD), which is even more pronounced in hypothyroid RA patients. An unfavourable cardiovascular risk profile conferred by a higher prevalence of the metabolic syndrome (MetS) and a higher Framingham risk score might explain this amplified cardiovascular morbidity. This study compared first, MetS (features) and second, the Framingham 10-year CVD risk in RA patients with hypothyroidism compared with euthyroid RA patients.RA patients participating in the CARRE investigation were divided into two groups: hypothyroid and euthyroid RA patients. MetS according to the National Cholesterol Education Program Third Adult Treatment Panel criteria and the Framingham risk score was compared between hypothyroid and non-hypothyroid CVD event-free RA patients.In total, 257 RA patients were included: 236 with RA (91.8%) and 21 with hypothyroid RA (8.2%), respectively. The prevalence of the MetS was significantly higher in hypothyroid RA patients (43%) compared with RA patients (20%). Moreover, female hypothyroid RA patients had a higher Framingham risk score compared with euthyroid RA patients. With RA patients as the reference category, the age and gender-adjusted prevalence odds ratio for the MetS was 3.5 (95% CI 1.3 to 9.1) in hypothyroid RA.Hypothyroid RA patients, particularly female patients, have a more unfavourable cardiovascular risk profile, reflected by an increased prevalence of the MetS and higher Framingham score, than euthyroid RA patients, suggesting a greater need for cardiovascular risk management in these patients to prevent future CVD events.
EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI): development of a consensus patient index for primary Sjögren's syndrome
Authors: Raphaèle Seror, Philippe Ravaud, Xavier Mariette, Hendrika Bootsma, Elke Theander, Arne Hansen, Manel Ramos-Casals, Thomas Dörner, Stefano Bombardieri, Eric Hachulla, Johan G Brun, Aike A Kruize, Sonja Praprotnik, Matija Tomsic, Jacques-Eric Gottenberg, Valerie Devauchelle, Salvatore Devita, Cristina Vollenweider, Thomas Mandl, Athanasios Tzioufas, Steven Carsons, Alain Saraux, Nurhan Sutcliffe, Claudio Vitali, Simon J Bowman
Journal: Annals of the Rheumatic Diseases (2011)

To develop a score for assessment of patients' symptoms in primary Sjögren's syndrome (SS): the EULAR SS Patient Reported Index (ESSPRI).Dryness, pain, somatic and mental fatigue were identified as the main symptoms of patients with primary SS, in studies developing the Profile of Fatigue and Discomfort (PROFAD) and Sicca Symptoms Inventory (SSI). It was suspected that a single 0-10 numerical scale for each domain was sufficient to assess these symptoms. These four scales were gathered to form the ESSPRI. 230 patients, from 12 countries completed the ESSPRI, SSI and PROFAD questionnaires and a 0-10 patient global assessment (PGA). Correlations between each symptom and PGA were obtained. Multiple regression modelling, using PGA as 'gold standard' was used to select domains and estimate their weights.PGA had good correlation with dryness, limb pain, fatigue and mental fatigue (r=0.49-0.59, all p<0.0001), but correlated less well with individual dryness features. In multivariate analysis, dryness, limb pain and fatigue, but not mental fatigue, were significantly associated with PGA; weights derived from the regression were identical for these three domains. Thus, ESSPRI was redefined as the mean of the three scales: dryness, limb pain and fatigue. Lastly, ESSPRI significantly correlated with PGA (r=0.70), PROFAD (r=0.73) and SSI (r=0.66).ESSPRI is a very simple index designed to measure patients' symptoms in primary SS. It has good construct validity and is well correlated with SSI and PROFAD. ESSPRI should now be validated for use as an outcome measure in clinical trials.
Measuring Disease Progression in Early Parkinson Disease
Authors: Sotirios A. Parashos, Sheng Luo, Kevin M. Biglan, Ivan Bodis-Wollner, Bo He, Grace S. Liang, G. Webster Ross, Barbara C. Tilley, Lisa M. Shulman
Journal: JAMA Neurology (2014)

Optimizing assessments of rate of progression in Parkinson disease (PD) is important in designing clinical trials, especially of potential disease-modifying agents.To examine the value of measures of impairment, disability, and quality of life in assessing progression in early PD.Inception cohort analysis of data from 413 patients with early, untreated PD who were enrolled in 2 multicenter, randomized, double-blind clinical trials.Participants were randomly assigned to 1 of 5 treatments (67 received creatine, 66 received minocycline, 71 received coenzyme Q10, 71 received GPI-1485, and 138 received placebo). We assessed the association between the rates of change in measures of impairment, disability, and quality of life and time to initiation of symptomatic treatment.Time between baseline assessment and need for the initiation of symptomatic pharmaceutical treatment for PD was the primary indicator of disease progression.After adjusting for baseline confounding variables with regard to the Unified Parkinson's Disease Rating Scale (UPDRS) Part II score, the UPDRS Part III score, the modified Rankin Scale score, level of education, and treatment group, we assessed the rate of change for the following measurements: the UPDRS Part II score; the UPDRS Part III score; the Schwab and England Independence Scale score (which measures activities of daily living); the Total Functional Capacity scale; the 39-item Parkinson's Disease Questionnaire, summary index, and activities of daily living subscale; and version 2 of the 12-item Short Form Health Survey Physical Summary and Mental Summary. Variables reaching the statistical threshold in univariate analysis were entered into a multivariable Cox proportional hazards model using time to symptomatic treatment as the dependent variable. More rapid change (ie, worsening) in the UPDRS Part II score (hazard ratio, 1.15 [95% CI, 1.08-1.22] for 1 scale unit change per 6 months), the UPDRS Part III score (hazard ratio, 1.09 [95% CI, 1.06-1.13] for 1 scale unit change per 6 months), and the Schwab and England Independence Scale score (hazard ratio, 1.29 [95% CI, 1.12-1.48] for 5 percentage point change per 6 months) was associated with earlier need for symptomatic therapy.AND RELEVANCE In early PD, the UPDRS Part II score and Part III score and the Schwab and England Independence Scale score can be used to measure disease progression, whereas the 39-item Parkinson's Disease Questionnaire and summary index, Total Functional Capacity scale, and the 12-item Short Form Health Survey Physical Summary and Mental Summary are not sensitive to change.clinicaltrials.gov Identifiers: NCT00063193 and NCT00076492.
Phase II Study of Gefitinib in Patients with Relapsed or Persistent Ovarian or Primary Peritoneal Carcinoma and Evaluation of Epidermal Growth Factor Receptor Mutations and Immunohistochemical Expression: A Gynecologic Oncology Group Study
Authors: Russell J. Schilder, Michael W. Sill, Xiaowei Chen, Kathleen M. Darcy, Steven L. Decesare, George Lewandowski, Roger B. Lee, Cletus A. Arciero, Hong Wu, Andrew K. Godwin
Journal: Clinical Cancer Research (2005)

Abstract Purpose: This phase II trial assessed the activity and tolerability of a daily oral dose of 500 mg gefitinib (ZD1839, Iressa) in patients with recurrent or persistent epithelial ovarian or primary peritoneal carcinoma, and explored the clinical value of determining the status of the epidermal growth factor receptor (EGFR). Experimental Design: Primary measure of efficacy was progression-free survival at 6 months. Mutations in exons 18 to 21 of EGFR and/or immunohistochemical expression of EGFR were evaluated in tumor specimens from patients enrolled in this trial as well as from patients not treated with gefitinib. Results: Twenty-seven of 30 (90%) patients were eligible and evaluable for analysis of gefitinib efficacy and toxicity. Of these, four survived progression-free &amp;gt;6 months with one objective response (4%). The most commonly observed grade 3 toxicities were dermatologic (15%, 4 of 27) and diarrhea (30%, 8 of 27). Specimens from 26 of 26 or 25 of 26 patients were evaluable for immunohistochemical or mutation analysis, respectively. The response rate for patients with EGFR-positive tumors was 9% (1 of 11). EGFR expression was associated with longer progression-free survival (P = 0.008) and possibly longer survival (P = 0.082). The patient with the only objective response had a mutation in the catalytic domain of the tumor's EGFR (P = 0.04). Among 32 invasive tumors from patients not treated with gefitinib, one exhibited a catalytic domain mutation. Conclusions: Gefitinib was well tolerated but had minimal activity in unscreened patients with recurrent ovarian or primary peritoneal carcinoma. Prescreening patients for activating mutations in EGFR may improve response rate to gefitinib. This report is the first to document activating mutations in catalytic domain of EGFR in 3.5% (2 of 57) of ovarian cancers.
Obesity and economic environments
Authors: Roland Sturm, Ruopeng An
Journal: CA A Cancer Journal for Clinicians (2014)

Abstract This review summarizes current understanding of economic factors during the obesity epidemic and dispels some widely held, but incorrect, beliefs. Rising obesity rates coincided with increases in leisure time (rather than increased work hours), increased fruit and vegetable availability (rather than a decline in healthier foods), and increased exercise uptake. As a share of disposable income, Americans now have the cheapest food available in history, which fueled the obesity epidemic. Weight gain was surprisingly similar across sociodemographic groups or geographic areas, rather than specific to some groups (at every point in time; however, there are clear disparities). It suggests that if one wants to understand the role of the environment in the obesity epidemic, one needs to understand changes over time affecting all groups, not differences between subgroups at a given time. Although economic and technological changes in the environment drove the obesity epidemic, the evidence for effective economic policies to prevent obesity remains limited. Taxes on foods with low nutritional value could nudge behavior toward healthier diets, as could subsidies/discounts for healthier foods. However, even a large price change for healthy foods could close only part of the gap between dietary guidelines and actual food consumption. Political support has been lacking for even moderate price interventions in the United States and this may continue until the role of environmental factors is accepted more widely. As opinion leaders, clinicians play an important role in shaping the understanding of the causes of obesity. CA Cancer J Clin 2014;64:337–350. © 2014 American Cancer Society.
Induction of integrin α2 in a highly bone metastatic human prostate cancer cell line: roles of RANKL and AR under three-dimensional suspension culture
Authors: Shabnam Ziaee, Leland WK Chung
Journal: Molecular Cancer (2014)

Prostate cancer (PCa) bone metastasis can be markedly enhanced by increased receptor activator of NF kappa-B ligand (RANKL) expression in PCa cells. Molecular mechanisms that account for the increased predilection of PCa for bone include increased bone turnover, promotion of PCa cell growth and survival in the bone environment, and recruitment of bystander dormant cells to participate in bone metastasis. The current study tests the hypothesis that PCa cells acquire high adhesion to bone matrix proteins, which controls PCa bone colonization, under the RANKL/RANK and AR axes. We used a highly bone metastatic RANKL-overexpressing LNCaP PCa cell line, LNCaPRANKL, as a model to pursue the molecular mechanisms underlying the increased adhesion of PCa cells to collagens. A three-dimensional (3-D) suspension PCa organoid model was developed. The functions of integrin α2 in cell adhesion and survival were evaluated by flow cytometry and western blot. AR expression and functionality were compared in 2-D monolayer versus 3-D suspension cultures using AR promoter- and PSA promoter-luciferase activity. AR role in cell adhesion was assessed using an adhesion assay. LNCaPRANKL cells were shown to adhere tightly to ColI matrix through increased α2 integrin expression. This increased adhesion, concomitant with activation of the FAK and Akt pathways, was further enhanced by culturing LNCaPRANKL cells in 3-D suspension. Under the influence of 3-D suspension culture, AR was restored in LNCaPRANKL cells via downregulation of AP-4 transcription factor, and supported increased α2 integrin expression and adhesion to ColI. 3-D suspension culture and in vivo PCa tumor growth restore AR through downregulation of AP-4, enhancing integrin α2 expression and adhesion to ColI which is rich in bone matrices. The interactions of PCa with ColI, mediated by integrin α2 and AR expression, could be a key molecular event accounting for PCa bone metastasis.
Case-Control Studies of Cancer Screening: Theory and Practice
Authors: Kathleen A. Cronin, Robert J. Connor, Philip C. Prorok, Douglas L. Weed
Journal: JNCI Journal of the National Cancer Institute (1998)

This review summarizes methodologic theories for the design of cancer screening case-control studies and examines the methods applied in studies published in English from 1980 through 1996. In addition to summarizing state-of-the-art methodologic approaches, we identify areas where obvious gaps exist between theory and practice, and we recommend potential areas where theory and methodology may need further development. In particular, we focus on three major areas: 1) the selection of case and control subjects, 2) the definition of exposure (i.e., exposure to the screening test), and 3) bias. Each area is considered carefully by summarizing current theory, reviewing cancer screening applications, and linking recommended methodologic approaches to those used in practice to identify areas where inconsistencies exist. In general, we found methodologic theory and practice in this field of research to be consistent. However, discrepancies were identified in the area of exposure definition, including the use of screening frequency and the use of a detectable, curable preclinical phase for case subjects as the exposure measures. Even when recommended methods were followed, a number of difficulties arose in practice. Specific concerns included the ability to carry out the following: identifying all case subjects within a source population, defining eligibility criteria to ensure that case and control subjects had equal access to screening during the exposure period, distinguishing between symptomatic and diagnostic tests, and controlling for self-selection bias. Careful scrutiny is warranted in all aspects of the design of cancer screening case-control studies, and caution is advised in the interpretation of study results.
Atrial Fibrillation Pathophysiology
Authors: Yu-ki Iwasaki, Kunihiro Nishida, Takeshi Kato, Stanley Nattel
Journal: Circulation (2011)

Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is an important contributor to population morbidity and mortality. An arrhythmia that is particularly common in the elderly, AF is growing in prevalence with the aging of the population. Our understanding of the basic mechanisms that govern AF occurrence and persistence has been increasing rapidly. This article reviews the basic pathophysiology of AF over a broad range of levels, touching on the tissue mechanisms that maintain the arrhythmia, the relationship between clinical presentation and basic mechanisms, ion channel and transporter abnormalities that lead to ectopic impulse formation, basic models and tissue determinants of reentry, ion channel determinants of reentry, the nature and roles of electric and structural remodeling, autonomic neural components, anatomic factors, interactions between atrial and ventricular functional consequences of AF, and the basic determinants of atrial thromboembolism. We then review the potential implications of the basic pathophysiology of the arrhythmia for its management. We first discuss consequences for improved rhythm control pharmacotherapy: targeting underlying conditions, new atrium-selective drug targets, new targets for focal ectopic source suppression, and upstream therapy aiming to prevent remodeling. We then review the implications of basic mechanistic considerations for rate control therapy, AF ablation, and the prevention of thromboembolic events. We conclude with some thoughts about the future of translational research related to AF mechanisms.
Tubedown Expression Correlates with the Differentiation Status and Aggressiveness of Neuroblastic Tumors
Authors: Darryl T. Martin, Robert L. Gendron, Jason A. Jarzembowski, Arie Perry, Margaret H. Collins, Chitra Pushpanathan, Ewa Miskiewicz, Valerie P. Castle, Hélène Paradis
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The discovery and validation of new prognostic factors and further refinement of risk group stratification are needed to improve clinical interpretation of neuroblastoma. Our laboratory isolated and characterized a developmentally regulated gene named TUBEDOWN against which we have raised a monoclonal antibody (OE5). Tubedown becomes down-regulated postnatally yet remains strongly expressed in some neuroblastomas. The purpose of this study is to define the utility of Tubedown expression as a new measure of the differentiation status and aggressiveness of neuroblastic tumors. Experimental Design: Tubedown protein expression was quantitatively assessed in neuroblastic tumors (neuroblastomas, ganglioneuroblastomas, and ganglioneuromas) and normal adrenal tissues using Western blot and OE5 immunohistochemistry. Regulation of Tubedown expression during retinoic acid–induced neuronal differentiation in neuroblastoma cell lines was assessed by Western blotting. Results: High levels of Tubedown expression are observed in tumors with significant neuroblastic component, unfavorable histopathology, advanced stage, high-risk group, and poor outcome. In contrast, more differentiated subsets of neuroblastic tumors, ganglioneuroblastomas with favorable histopathology and ganglioneuromas, express low levels of Tubedown. In vitro, marked retinoic acid–induced neuronal differentiation responses of neuroblastoma cells are associated with a significant decrease in Tubedown expression, whereas limited neuronal differentiation responses to retinoic acid were associated with little or no decrease in Tubedown expression. Conclusions: Our results indicate that the levels of Tubedown expression are linked to the differentiation status and aggressiveness of neuroblastic tumors and represent an independent prognostic factor for neuroblastoma. Tubedown expression may be useful to more accurately define different neuroblastic tumor subsets and ultimately provide more adequate assessment and treatment for neuroblastoma patients.
Response to Letter Regarding Article, “Complications Associated With Revision of Sprint Fidelis Leads: Report From the Canadian Heart Rhythm Society Device Advisory Committee”
Authors: Ratika Parkash, Eugene Crystal, Jamil Bashir, Christopher Simpson, David Birnie, Laurence Sterns, Derek Exner, Bernard Thibault, Sean Connors, Jeffrey S. Healey, Jean Champagne, Doug Cameron, Iqwal Mangat, Atul Verma, Kevin Wolfe, Vidal Essebag, Teresa Kus, Felix Ayala-Paredes, Ted Davies, Shubhayan Sanatani, Robert Gow, Bernard Coutu, Soori Sivakumaran, Elizabeth Stephenson, Andrew Krahn
Journal: Circulation (2011)
Unsolved issues in S-modulin/recoverin study
Authors: Satoru Kawamura
Journal: Behavioral and Brain Sciences (1995)

Abstract S-Modulin is a frog homolog of recoverin. The function and the underlying mechanism of the action of these proteins are now understood in general. However, there remain some unsolved issues including; two distinct effects of S-modulin; Ca 2+ -dependent binding of S-modulin to membranes and a possible target protein; S-modulin-like proteins in other neurons. These issues are considered in this commentary.
Effect of Short-term Cardiovascular Conditioning and Low-Fat Diet on Myocardial Blood Flow and Flow Reserve
Authors: Johannes Czernin, R. James Barnard, Karl T. Sun, Janine Krivokapich, Egbert Nitzsche, Deborah Dorsey, Michael E. Phelps, Heinrich R. Schelbert
Journal: Circulation (1995)

Background Cardiovascular conditioning reduces resting myocardial oxygen demand by lowering systolic blood pressure and heart rate. Lower myocardial oxygen demand at rest would be expected to be associated with a decrease in resting myocardial blood flow and, consequently, an increase in myocardial flow reserve as the ratio of hyperemic to resting blood flow. However, the effect of controlled exercise together with a low-lipid diet on myocardial blood flow and flow reserve has not been examined in humans. Methods and Results Myocardial blood flow at rest and after dipyridamole-induced hyperemia (0.56 mg/kg IV) was quantified with [ 13 N]ammonia and positron emission tomography in 13 volunteers before and upon completion of a 6-week program of cardiovascular conditioning and a low-fat diet. Exercise capacity and serum lipid profiles were also assessed at the start and finish of the program. Eight normal volunteers of similar age not participating in the conditioning program served as a control group. Cardiovascular conditioning lowered the resting rate-pressure product (8859±2128 versus 7450±1496, P &lt;.001), serum cholesterol (217±36 versus 181±26 mg/dL), LDL cholesterol (140±32 versus 114±24 mg/dL), and triglycerides (145±53 versus 116±33 mg/dL, all P &lt;.05). Exercise tolerance (metabolic equivalent of the task, METs) improved significantly from 10.0±3.0 to 14.4±3.6 ( P &lt;.01). Resting blood flow decreased (0.78±0.18 versus 0.69±0.14 mL · g −1 · min −1 , P &lt;.05), whereas hyperemic blood flow increased (2.06±0.35 versus 2.25±0.40 mL · g −1 · min −1 , P &lt;.05), resulting in an improved myocardial flow reserve (2.82±1.07 versus 3.39±0.91, P &lt;.05). Overall, the myocardial flow reserve was significantly related to exercise performance (METs). In the control group, no changes in resting rate-pressure product, serum cholesterol levels, exercise performance, resting or hyperemic myocardial blood flow, or flow reserve were observed. Conclusions Short-term cardiovascular conditioning together with a low-fat diet results in an improved myocardial flow reserve by lowering resting blood flow and increasing coronary vasodilatory capacity. These changes are associated with an improved exercise capacity and may offer a protective effect in patients with coronary artery disease.