tbuckley/cabot-search huggingface dataset:
Value of endoscopy and MRI for predicting intestinal surgery in patients with Crohn's disease in the era of biologics
Authors: A Jauregui-Amezaga, J Rimola, I Ordás, S Rodríguez, A Ramírez-Morros, M Gallego, M C Masamunt, J Llach, B González-Suárez, E Ricart, J Panés
Journal: Gut (2014)

<h3>Objective</h3> Severe endoscopic lesions (SEL) in patients with colonic Crohn9s disease (CD) have been linked to higher risk of colectomy. The aims of this study were to reassess the predictive value of colonoscopy compared against MRI for requirement of resection surgery in patients with CD and determine the influence of current therapeutic options. <h3>Design</h3> In this single-centre, observational, prospective, longitudinal study, patients with an established diagnosis of CD and suspected activity were included. After baseline assessment, including colonoscopy and MRI, patients were followed until resection surgery or the end of study. <h3>Results</h3> 112 patients were eligible for analysis. Ulcers were present in 94/112 (84%) of patients at colonoscopy (SELs in 51/112 (46%)) and stenosis in 38/112 (34%). MRI identified ulcers in 79/112 (71%) of patients, stenosis in 36/112 (32%) and intra-abdominal fistulae in 20/112 (18%). Surgical resection requirements (29/112 (26%)) were not associated with the presence of SELs at colonoscopy. The presence of stenosis (p&lt;0.001) or intra-abdominal fistulae (p&lt;0.001) at MRI correlated with a higher risk of surgery. In the multivariate analysis, perianal disease (OR 9 (2 to 39), p=0.003), stenosis (OR 3.4 (1 to 11), p=0.04) and fistulae at MRI (OR 10.6 (2 to 46), p=0.002) increased the risk of abdominal resection surgery, while months under immunomodulators (OR 0.94 (0.90 to 0.98), p=0.002) and/or antitumor necrosis factor (anti-TNF) therapy (OR 0.97 (0.94 to 1), p=0.04) during follow-up decreased this risk. <h3>Conclusions</h3> Perianal disease, stenosis and/or intra-abdominal fistulae at MRI independently predict an increased risk of resection surgery in patients with CD, whereas immunosuppressants and/or anti-TNF therapy reduce such risk. Under current therapeutic strategies, the presence of SELs is not a predictor of resection surgery in patients with CD.
Stepping up the controller medication in asthma patients: Impact of various treatment options on costs
Authors: Mohsen Sadatsafavi, Pierrick Bedouch, Mark FitzGerald, Carlo Narra, Larry Lynd
Journal: European Respiratory Journal (2011)

Introduction: To compare asthma-related costs among adults who step-up their controller medication.

Methods: A population-based study was conducted using the administrative health data of British Columbia, Canada (1997 to 2007). Hospitalization, physician visits, and prescription records were used to identify asthma patients (age 14-65) and calculate direct costs. Four cohorts were constructed as those who: increased the dose of inhaled corticosteroids (ICS+ group), switched to ICS/long-acting beta-agonist (LABA) in a single formulation (ICS/LABA group), added LABA in separate formulations (ICS+LABA group), or added leukotriene receptor antagonist (ICS+LRA group). The outcome was the direct cost of asthma (2008 CAD) in the year after the step-up, adjusted for multiple demographic, resource use, and comorbidty variables from the previous year.

Results: 32,640 patients (average age 42.3; 60.3% female) were included (7,115 ICS+, 19,457 ICS/LABA, 4,086 ICS+LABA, and 1,982 ICS/LRA). The average costs of asthma for the year after the index date for the ICS+ group was $509. Compared to ICS+, all other groups had significantly positive incremental costs: +$358.0 for ICS/LABA, +$504.3 for ICS+LABA, and +$541.6 for ICS/LRA (all P-values<0.01). Higher age, higher resource use, and higher cumulative dose of rescue medication in the year prior to the step-up date were predictors of higher costs after the step-up date (all p<0.01).

Conclusions: Based on relatively large sample and adjusted for several potential confounders, increasing ICS dose as a step-up approach was associated with the lower costs compared to addition of a second class of controller medication.
Symptoms limiting activity in cancer patients with breathlessness on exertion: ask about muscle fatigue
Authors: A Wilcock, M Maddocks, M Lewis, R England, C Manderson
Journal: Thorax (2007)

<h3>Objective:</h3> To report the rates and predictors of progression from normal cognition to either mild cognitive impairment (MCI) or dementia using standardized neuropsychological methods. <h3>Methods:</h3> A prospective cohort of patients diagnosed with Parkinson disease (PD) and baseline normal cognition was assessed for cognitive decline, performance, and function for a minimum of 2 years, and up to 6. A panel of movement disorders experts classified patients as having normal cognition, MCI, or dementia, with 55/68 (80.9%) of eligible patients seen at year 6. Kaplan-Meier curves and Cox proportional hazard models were used to examine cognitive decline and its predictors. <h3>Results:</h3> We enrolled 141 patients, who averaged 68.8 years of age, 63% men, who had PD on average for 5 years. The cumulative incidence of cognitive impairment was 8.5% at year 1, increasing to 47.4% by year 6. All incident MCI cases had progressed to dementia by year 5. In a multivariate analysis, predictors of future decline were male sex (<i>p</i> = 0.02), higher Unified Parkinson9s Disease Rating Scale motor score (<i>p</i> ≤ 0.001), and worse global cognitive score (<i>p</i> &lt; 0.001). <h3>Conclusions:</h3> Approximately half of patients with PD with normal cognition at baseline develop cognitive impairment within 6 years and all new MCI cases progress to dementia within 5 years. Our results show that the transition from normal cognition to cognitive impairment, including dementia, occurs frequently and quickly. Certain clinical and cognitive variables may be useful in predicting progression to cognitive impairment in PD.
Role of Focal Adhesion Kinase in Regulating YB–1–Mediated Paclitaxel Resistance in Ovarian Cancer
Authors: Yu Kang, Wei Hu, Cristina Ivan, Heather J. Dalton, Takahito Miyake, Chad V. Pecot, Behrouz Zand, Tao Liu, Jie Huang, Nicholas B. Jennings, Rajesha Rupaimoole, Morgan Taylor, Sunila Pradeep, Sherry Y. Wu, Chunhua Lu, Yunfei Wen, Jianfei Huang, Jinsong Liu, Anil K. Sood
Journal: JNCI Journal of the National Cancer Institute (2013)

We previously found focal adhesion kinase (FAK) inhibition sensitizes ovarian cancer to taxanes; however, the mechanisms are not well understood.We characterized the biologic response of taxane-resistant and taxane-sensitive ovarian cancer models to a novel FAK inhibitor (VS-6063). We used reverse-phase protein arrays (RPPA) to identify novel downstream targets in taxane-resistant cell lines. Furthermore, we correlated clinical and pathological data with nuclear and cytoplasmic expression of FAK and YB-1 in 105 ovarian cancer samples. Statistical tests were two-sided, and P values were calculated with Student t test or Fisher exact test.We found that VS-6063 inhibited FAK phosphorylation at the Tyr397 site in a time- and dose-dependent manner. The combination of VS-6063 and paclitaxel markedly decreased proliferation and increased apoptosis, which resulted in 92.7% to 97.9% reductions in tumor weight. RPPA data showed that VS-6063 reduced levels of AKT and YB-1 in taxane-resistant cell lines. FAK inhibition enhanced chemosensitivity in taxane-resistant cells by decreasing YB-1 phosphorylation and subsequently CD44 in an AKT-dependent manner. In human ovarian cancer samples, nuclear FAK expression was associated with increased nuclear YB-1 expression (χ²) = 37.7; P < .001). Coexpression of nuclear FAK and YB-1 was associated with statistically significantly worse median overall survival (24.9 vs 67.3 months; hazard ratio = 2.64; 95% confidence interval = 1.38 to 5.05; P = .006).We have identified a novel pathway whereby FAK inhibition with VS-6063 overcomes YB-1-mediated paclitaxel resistance by an AKT-dependent pathway. These findings have implications for clinical trials aimed at targeting FAK.
Screening for gastric cancer in Asia: current evidence and practice
Authors: Wai K Leung, Ming-shiang Wu, Yasuo Kakugawa, Jae J Kim, Khay-guan Yeoh, Khean Lee Goh, Kai-chun Wu, Deng-chyang Wu, Jose Sollano, Udom Kachintorn, Takuji Gotoda, Jaw-town Lin, Wei-cheng You, Enders KW Ng, Joseph JY Sung
Journal: The Lancet Oncology (2008)
Identifying the Effects of Environmental and Policy Change Interventions on Healthy Eating
Authors: Deborah J. Bowen, Wendy E. Barrington, Shirley A.A. Beresford
Journal: Annual Review of Public Health (2015)

Obesity has been characterized as a disease. Strategies to change the incidence and prevalence of this disease include a focus on changing physical and social environments, over and above individual-level strategies, using a multilevel or systems approach. We focus our attention on evidence published between 2008 and 2013 on the effectiveness of interventions in nutrition environments, i.e., environmental interventions designed to influence the intake of healthful foods and amount of energy consumed. An overarching socioecological framework that has guided much of this research was used to characterize different types of environmental strategies. Intervention examples in each area of the framework are provided with a discussion of key findings and related conceptual and methodological issues. The emphasis in this review is on adults, but clearly this literature is only one part of the picture. Much research has been focused on child-specific interventions, including environmental interventions. Some evidence suggests effectiveness of policy-based or other types of interventions that aim to regulate or restructure environments to promote healthy dietary choices, and these strategies would apply to both children and adults. Opportunities to evaluate these policy changes in adults' social and physical environments are rare. Much of the existing research has been with children. As conceptual and methodological issues continue to be identified and resolved, we hope that future research in this domain will identify environmental strategies that can be included in intervention toolboxes to build healthy nutrition environments for both adults and children.
Changes in the Ca <sup>2+</sup> -Activated K <sup>+</sup> Channels of the Coronary Artery During Left Ventricular Hypertrophy
Authors: Nari Kim, Joonyong Chung, Euiyong Kim, Jin Han
Journal: Circulation Research (2003)

It has been suggested that impairment of smooth muscle cell (SMC) function by alterations in the Ca2+-activated K+ (KCa) channels accounts for the reduction in coronary reserve during left ventricular hypertrophy (LVH). However, this hypothesis has not been fully investigated. The main goal of this study was to assess whether the properties of KCa channels in coronary SMCs were altered during LVH. In patch-clamp experiments, the whole-cell currents of the KCa channels were reduced during LVH. The unitary current amplitude and open probability for the KCa channels were significantly reduced in LVH patches compared with control patches. The concentration-response curve of the KCa channel to [Ca2+]i was shifted to the right. Inhibition of the KCa channels by tetraethylammonium (TEA) was more pronounced in LVH cells than in control cells. Western blot analysis indicated no differences in KCa channel expression between the control and LVH coronary SM membranes. In contraction experiments, the effect of high K+ concentration on the resting tension of the LVH coronary artery was greater than on that of the control. The effect of TEA on the resting tension of the LVH coronary artery was reduced compared with the effect on the control. Our findings imply a novel mechanism for reduced coronary reserve during LVH.
Bronchoscopic findings in children with non-cystic fibrosis chronic suppurative lung disease
Authors: A B Chang
Journal: Thorax (2002)

Published data on the frequency and types of flexible bronchoscopic airway appearances in children with non-cystic fibrosis bronchiectasis and chronic suppurative lung disease are unavailable. The aims of this study were to describe airway appearances and frequency of airway abnormalities and to relate these airway abnormalities to chest high resolution computed tomography (cHRCT) findings in a cohort of children with non-cystic fibrosis chronic suppurative lung disease (CSLD).Indigenous children with non-cystic fibrosis CSLD (>4 months moist and/or productive cough) were prospectively identified and collected over a 2.5 year period at two paediatric centres. Their medical charts and bronchoscopic notes were retrospectively reviewed.In all but one child the aetiology of the bronchiectasis was presumed to be following a respiratory infection. Thirty three of the 65 children with CSLD underwent bronchoscopy and five major types of airway findings were identified (mucosal abnormality/inflammation only, bronchomalacia, obliterative-like lesion, malacia/obliterative-like combination, and no macroscopic abnormality). The obliterative-like lesion, previously undescribed, was present in 16.7% of bronchiectatic lobes. Structural airway lesions (bronchomalacia and/or obliterative-like lesion) were present in 39.7% of children. These lesions, when present, corresponded to the site of abnormality on the cHRCT scan.Structural airway abnormality is commonly found in children with post-infectious bronchiectasis and a new bronchoscopic finding has been described. Airway abnormalities, when present, related to the same lobe abnormality on the cHRCT scan. How these airway abnormalities relate to aetiology, management strategy, and prognosis is unknown.
Association of two silent polymorphisms of platelet glycoprotein la/lla receptor with risk of myocardial infarction: a case-control study
Authors: Khatereh Moshfegh, Walter A Wuillemin, Maurice Redondo, Bernhard Lämmle, Jürg H Beer, Sabina Liechti-Gallati, Beat J Meyer
Journal: The Lancet (1999)
Cytostatic and anti-angiogenic effects of temsirolimus in refractory mantle cell lymphoma
Authors: Li Wang, Wen-Yu Shi, Zhi-Yuan Wu, Mariana Varna, Ai-Hua Wang, Li Zhou, Li Chen, Zhi-Xiang Shen, He Lu, Wei-Li Zhao, Anne Janin
Journal: Journal of Hematology & Oncology (2010)

Abstract Mantle cell lymphoma (MCL) is a rare and aggressive type of B-cell non-Hodgkin's lymphoma. Patients become progressively refractory to conventional chemotherapy, and their prognosis is poor. However, a 38% remission rate has been recently reported in refractory MCL treated with temsirolimus, a mTOR inhibitor. Here we had the opportunity to study a case of refractory MCL who had tumor regression two months after temsirolimus treatment, and a progression-free survival of 10 months. In this case, lymph node biopsies were performed before and six months after temsirolimus therapy. Comparison of the two biopsies showed that temsirolimus inhibited tumor cell proliferation through cell cycle arrest, but did not induce any change in the number of apoptotic tumor cells. Apart from this cytostatic effect, temsirolimus had an antiangiogenic effect with decrease of tumor microvessel density and of VEGF expression. Moreover, numerous patchy, well-limited fibrotic areas, compatible with post-necrotic tissue repair, were found after 6-month temsirolimus therapy. Thus, temsirolimus reduced tumor burden through associated cytostatic and anti-angiogenic effects. This dual effect of temsirolimus on tumor tissue could contribute to its recently reported efficiency in refractory MCL resistant to conventional chemotherapy.
Pyrrolidine dithiocarbamate attenuates the development of organ failure induced by zymosan in mice
Authors: Salvatore Cuzzocrea, Antonietta Rossi, Barbara Pisano, Rosanna Di Paola, Tiziana Genovese, Nimesh S. A. Patel, Elisabetta Cuzzocrea, Angela Ianaro, Lidia Sautebin, Francesco Fulia, Prabal K. Chatterjee, Achille P. Caputi, Christoph Thiemermann
Journal: Intensive Care Medicine (2003)
Reliability, Validity, and Classification Accuracy of a Measure of DSM-IV Diagnostic Criteria for Pathological Gambling
Authors: Randy Stinchfield
Journal: American Journal of Psychiatry (2002)

The purpose of this study was to measure the reliability, validity, and classification accuracy of the DSM-IV diagnostic criteria for pathological gambling.Participants in this study were drawn from two sources: 803 men and women from the general adult population of Minnesota and 259 men and women who were admitted to a gambling treatment program. A 19-item measure of the DSM-IV diagnostic criteria for pathological gambling was administered, along with other validity measures.The DSM-IV diagnostic criteria were found to be reliable and valid. With a standard cutoff score of 5, DSM-IV criteria yielded satisfactory classification accuracy results; however, a cutoff score of 4 made modest improvements in classification accuracy and, most important, reduced the rate of false negatives.The DSM-IV diagnostic criteria for pathological gambling, when operationalized into questions, demonstrated satisfactory reliability, validity, and classification accuracy, and a cutoff score of 4 improved diagnostic precision.
Brain drain from developing countries: how can brain drain be converted into wisdom gain?
Authors: S. Dodani
Journal: Journal of the Royal Society of Medicine (2005)

Brain drain is defined as the migration of health personnel in search of the better standard of living and quality of life, higher salaries, access to advanced technology and more stable political conditions in different places worldwide. This migration of health professionals for better opportunities, both within countries and across international borders, is of growing concern worldwide because of its impact on health systems in developing countries. Why do talented people leave their countries and go abroad? What are the consequences of such migrations especially on the educational sector? What policies can be adopted to stem such movements from developing countries to developed countries? This article seeks to raise questions, identify key issues and provide solutions which would enable immigrant health professionals to share their knowledge, skills and innovative capacities and thereby enhancing the economic development of their countries.
Maternal Insulin Therapy Increases Fetal Endothelial Progenitor Cells During Diabetic Pregnancy
Authors: Gian Paolo Fadini, Ilenia Baesso, Carlo Agostini, Emily Cuccato, Giovanni Battista Nardelli, Annunziata Lapolla, Angelo Avogaro
Journal: Diabetes Care (2008)

Endothelial progenitor cells (EPCs) are bone marrow–derived cells involved in endothelial homeostasis and angiogenesis. Reduction and dysfunction of EPCs have been associated with the development of atherosclerosis and diabetic complications (1,2).

Recent studies in human pregnancies suggest that a mother's EPCs are involved in the physiologic vascular remodeling of systemic and utero-placental circulation (3,4). Hyperglycemia induces dysfunction and apoptosis of EPCs (5); this may impair the development or maturation of the utero-placental circulation, causing maladaptive responses during diabetic pregnancies. Indeed, EPCs have been shown to be dysregulated in pregnant women with diabetes (4).

Little is known about the effects of maternal factors on fetal EPCs. One study showed reduced cord blood EPCs in severe preeclampsia (6), but there were no data on diabetes. This study was undertaken to evaluate quantitative alterations of cord blood progenitor cells during diabetic pregnancies.

We enrolled 24 nondiabetic and 17 diabetic pregnant women: two had pregravidic type 1 diabetes and 15 had gestational diabetes mellitus (GDM). GDM was diagnosed according to the American Diabetes Association guidelines (7). Provided that informed consent was obtained from the mother, at time of delivery 5 ml of umbilical vein cord blood was collected into heparin tubes for progenitor cell count. The following data about the mother were recorded: age, pregravidic BMI, weight increase, smoking habit, family history of cardiovascular disease, arterial blood pressure, and type of antidiabetic treatment. Before labor, blood samples were collected for determination of plasma glucose levels, leukocyte count, fibrinogen levels, and total cholesterol and triglycerides concentrations. After delivery, gestational age, neonatal …
Treatment outcome and survival in participants of phase I oncology trials carried out from 2003 to 2006 at Institut Gustave Roussy
Authors: A. Italiano, C. Massard, R. Bahleda, A.-L. Vataire, E. Deutsch, N. Magné, J.-P. Pignon, G. Vassal, J.-P. Armand, J.-C. Soria
Journal: Annals of Oncology (2007)
Sensitization of Arteries, Veins, and Small Vessels to Norepinephrine After Cocaine
Authors: FRANCOIS M. ABBOUD, JOHN W. ECKSTEIN, BEN G. ZIMMERMAN, MICHAEL H. GRAHAM
Journal: Circulation Research (1964)

The effects of cocaine on the responses of arteries, veins, and small vessels to norepinephrine were studied. Intra-arterial norepinephrine was injected or infused into perfused forelegs of dogs. Angiotensin and serotonin were used as agonists. The effects of postganglionic sympathetic stimulation and of intra-arterial tyramine were tested also. Cocaine in doses of 0.5, 5.0, and 10 mg/kg IV sensitized the arterial and venous segments to norepinephrine; the responses of small vessels were not augmented significantly. The effects of angiotensin and serotonin were not increased. The vasoconstrictor effect of weak and strong submaximal postganglionic sympathetic nerve stimulations was reduced and that of intra-arterial tyramine was suppressed after cocaine. The results allow us to conclude that vascular supersensitivity to norepinephrine after cocaine is not a uniform phenomenon but it is restricted to certain vascular segments. The reason for the sensitization of arteries and veins but not small vessels is unknown. The observations are discussed in light of the recent hypothesis proposed by Furchgott et al on the mechanism of action of cocaine.
Calcium in renal cells. Modulation of calcium-dependent activation of phospholipase A2.
Authors: J V Bonventre
Journal: Environmental Health Perspectives (1990)

Calcium has been implicated as a regulatory factor in many physiological and pathophysiological processes in the renal cell. Under physiological conditions, the cytosolic free calcium concentration is maintained at approximately 100 nM. Most of the releasable cell Ca2+ resides in the nonmitochondrial compartments. In addition to the plasma membrane Ca2+ transport processes, there is a high-affinity, low-capacity buffering capability of nonmitochondrial organelles and a lower-affinity high-capacity mitochondrial Ca2+ buffering capability. A critical enzymatic effector of Ca2+ action in the cell is phospholipase A2. By using digitonin-permeabilized renal mesangial cells, the [Ca2+] dependency of phospholipase A2 was characterized. The [Ca2+] sensitivity was insufficient to explain the phospholipase A2 activation observed with vasopressin. In both intact cells, as well as permeabilized cells, it was found that protein kinase C activation markedly enhanced the Ca2+ calmodulin-dependent activation of phospholipase A2. In response to platelet-derived growth factor, it was found that arachidonic acid release preceded phospholipase C activation. This suggests that other effectors besides Ca2+ and protein kinase C may also be important for phospholipase A2 activation. In an experimental model designed to mimic postischemic reperfusion damage to renal mitochondria, it was demonstrated that reactive oxygen species act synergistically with Ca2+ to activate mitochondrial phospholipase A2, which mediates damage to site I of the electron transport chain, the F1F0 ATPase, and the adenine nucleotide translocase.(ABSTRACT TRUNCATED AT 250 WORDS)