tbuckley/cabot-search huggingface dataset:
Abstract 512: Cardiac Metabolic Adaptation during Chronic Exercise is Independent of PGC-1 Signaling
Authors: Michael Schwarzer, Gracjan Pytel, Heiko Bugger, Andrea Schrepper, Maria Schoepe, Christian Riehle, Torsten Doenst
Journal: Circulation (2007)

PGC-1alpha is a transcriptional coactivator that regulates gene expression of mitochondrial proteins and energy metabolic enzymes. In skeletal muscle, PGC-1alpha is induced by endurance training and thought to mediate the energy metabolic adaptation to exercise. We investigated the role of PGC-1alpha signaling in metabolic adaptation of the heart in response to exercise. Male Sprague Dawley rats were trained on treadmills for 10 weeks, resulting in increased left ventricular posterior wall diameter (1.84±0.13 vs. 2.35±0.15 mm, p&lt;0.05), indicating physiological hypertrophy. Gene expression of PGC-1alpha and beta and their transcription factors (NRF1&amp;2, ERRalpha, TFAm) was not different compared to controls. Similarly, expression of OXPHOS genes (Ndufa10, Uqcrc2, COXIV) was unchanged in treadmill-trained hearts. In accordance with gene expression, state 3 respiration of isolated mitochondria was not different from controls, using palmitoyl-carnitine, pyruvate, or glutamate as substrates (natomsO/min/mg protein: Control PC 121±30, Pyr 58±6, Glu 203±42). In contrast, mitochondrial state 3 respiration of the oxidative soleus muscle was tripled with all substrates (natomsO/min/mg protein: PC 150±18 vs. 453±125, Pyr 95±23 vs. 310±37, Glu 115±12 vs. 280±23, p&lt;0.05). Since PGC-1alpha signaling may also regulate substrate oxidation, we investigated oxidation of fatty acids (FAO) and glucose (GO) in the isolated working rat heart using 0.4mM oleate and 5mM glucose. FAO was not different between groups (μmol/min/gdw: 0.99±0.07 vs. 0.92±1.10). While expression of PPARalpha was increased in treadmill trained rats (+49%, p&lt;0.05), FAO genes were not differentially expressed (MCAD, LCAD, CPT1). GO was 40% lower in trained hearts (0.38±0.08 vs. 0.23±0.06 μmol/min/g dry, n.s.) and was accompanied by a trend towards increased PDK4 expression (+90%, p=0.059). The response to insulin was normal. Cardiac power in trained working hearts was also normal. We conclude that PGC-1 signaling may not mediate the cardiac hypertrophic response to exercise. In contrast to skeletal muscle, respiratory capacity is not increased in heart muscle after exercise. The metabolic phenotype of hypertrophied hearts in response to exercise is surprisingly normal.
Microsatellite Instability and Frameshift Mutations in BAX and Transforming Growth Factor-β RII Genes Are Very Uncommon in Acute Lymphoblastic Leukemia In Vivo But Not in Cell Lines
Authors: Jan J. Molenaar, Bénédicte Gérard, Cécile Chambon-Pautas, Hélène Cavé, Michel Duval, Etienne Vilmer, Bernard Grandchamp
Journal: Blood (1998)
Abstract P103: Dietary Patterns in South Asian Indians in the United States: An Analysis of the Metabolic Syndrome and Atherosclerosis in South Asians Living in America (MASALA) Study
Authors: Meghana D Gadgil, Cheryl A Anderson, Namratha R Kandula, Alka Kandula
Journal: Circulation (2013)

Background: Dietary patterns contribute to cardiovascular disease (CVD) risk. South Asians, individuals from the Indian subcontinent, have earlier onset, more severe and prevalent CVD than many oth...
The enduring psychosocial consequences of mania and depression
Authors: W Coryell, W Scheftner, M Keller, J Endicott, J Maser, G L Klerman
Journal: American Journal of Psychiatry (1993)

The authors sought to determine the scope, severity, and persistence of psychosocial impairment arising from bipolar and unipolar affective disorder.Patients with bipolar (N = 148) or unipolar (N = 240) major affective disorder were assessed as they sought treatment and again after a 5-year follow-up. Concurrently, parents, siblings, and adult children underwent similar assessments and were followed for 6 years. To quantify the impact of affective disorder, probands were individually matched to relatives who had no lifetime history of affective disorder. Sixty-nine relatives who were depressed at intake constituted a separate, nonclinical study group and were also matched to relatives who were well.Both unipolar and bipolar patients began follow-up with deficits in annual income. Relative to comparison subjects, affective disorder groups were significantly more likely to report declines in job status and income at the end of follow-up and significantly less likely to report improvements. Similarly, both bipolar and unipolar patients showed significant deficits in nearly all other areas of psychosocial functioning measured at follow-up. Except for relationships with spouses, deficits did not differ significantly by polarity. Surprisingly, probands with recovery sustained throughout the final 2 years of follow-up also showed severe and widespread impairment. Relatives with major depression exhibited substantial deficits on follow-up, but job status and income were not significantly affected.The psychosocial impairment associated with mania and major depression extends to essentially all areas of functioning and persists for years, even among individuals who experience sustained resolution of clinical symptoms.
Fatal Marrow Aplasia After Treatment with Carbimazole
Authors: C. D. Burrell
Journal: BMJ (1956)

EDICORNAL JOURNAL~~~~~~~~~~~~~~~~The toxic effects of carbimazole can usually be readily recognized and controlled, and after serious toxic effects drug therapy can be continued where necessary with perchlorate.It is probably better to reserve perchlorate for this role on account of its potentially less smooth antithyroid control.
Abstract 976: Hyperpolarized Mitochondria in Right Ventricular Hypertrophy: a Target for Ventricular-Specific Therapies
Authors: Jayan Nagendran, Vikram Gurtu, Jason R Dyck, David B Ross, Ivan M Rebeyka, Evangelos D Michelakis
Journal: Circulation (2007)

Objectives : The right ventricle (RV) fails quickly after increases in its afterload (pulmonary hypertension) compared to the LV (systemic hypertension). We hypothesized that the suboptimal performance of the hypertrophied RV (RVH) is caused by metabolic adaptation during hypertrophy. Mitochondria regulate metabolism, and mitochondrial membrane potential (ΔΨm) is a surrogate for mitochondrial function. Methods/Results : We measured ΔΨm in normal and hypertrophied myocardial specimens from 11 patients and in a rat model of RVH, using Tetramethylrhodamine methyl ester, a positively-charged dye that selectively localizes within the negatively charged mitochondria. ΔΨm was significantly higher in the normal LV compared to normal RV, and was the highest in RVH, both at the myocardium and isolated cardiomyocyte levels (p&lt;0.01 for both). The increase in ΔΨm was recapitulated in an in vitro model of hypertrophy, where isolated neonatal cardiomyocytes were exposed to phenylephrine. This increase in ΔΨm was reversed by both a direct inhibitor of NFAT (Nuclear-Factor-of-Activated-T-lymphocytes, a transcription factor that regulates cardiac metabolism in development and hypertrophy) and Dichloroacetate (DCA, a metabolic modulator that has been shown to depolarize mitochondria and inhibit NFAT, reversing the phenotype of disease in both cancer and pulmonary hypertension) (p&lt;0.01 for both). In ex-vivo Langendorff perfusions DCA acutely increased RV inotropy in rats with RVH (p&lt;0.01) but not normal RVs, suggesting that the increased ΔΨm in RVH might be associated with its suboptimal performance in patients with pulmonary hypertension. Conclusions : The significant differences in ΔΨm between RV, LV, and RVH, can be targeted metabolically by DCA to improve contractility in RVH and provide a framework for development of novel RV-specific therapies.
Health, Health Inequality, and Cost Impacts of Annual Increases in Tobacco Tax: Multistate Life Table Modeling in New Zealand
Authors: Tony Blakely, Linda J. Cobiac, Christine L. Cleghorn, Amber L. Pearson, Frederieke S. van der Deen, Giorgi Kvizhinadze, Nhung Nghiem, Melissa McLeod, Nick Wilson
Journal: PLoS Medicine (2015)

Background Countries are increasingly considering how to reduce or even end tobacco consumption, and raising tobacco taxes is a potential strategy to achieve these goals. We estimated the impacts on health, health inequalities, and health system costs of ongoing tobacco tax increases (10% annually from 2011 to 2031, compared to no tax increases from 2011 ["business as usual," BAU]), in a country (New Zealand) with large ethnic inequalities in smoking-related and noncommunicable disease (NCD) burden. Methods and Findings We modeled 16 tobacco-related diseases in parallel, using rich national data by sex, age, and ethnicity, to estimate undiscounted quality-adjusted life-years (QALYs) gained and net health system costs over the remaining life of the 2011 population (n = 4.4 million). A total of 260,000 (95% uncertainty interval [UI]: 155,000–419,000) QALYs were gained among the 2011 cohort exposed to annual tobacco tax increases, compared to BAU, and cost savings were US$2,550 million (95% UI: US$1,480 to US$4,000). QALY gains and cost savings took 50 y to peak, owing to such factors as the price sensitivity of youth and young adult smokers. The QALY gains per capita were 3.7 times greater for Māori (indigenous population) compared to non-Māori because of higher background smoking prevalence and price sensitivity in Māori. Health inequalities measured by differences in 45+ y-old standardized mortality rates between Māori and non-Māori were projected to be 2.31% (95% UI: 1.49% to 3.41%) less in 2041 with ongoing tax rises, compared to BAU. Percentage reductions in inequalities in 2041 were maximal for 45–64-y-old women (3.01%). As with all such modeling, there were limitations pertaining to the model structure and input parameters. Conclusions Ongoing tobacco tax increases deliver sizeable health gains and health sector cost savings and are likely to reduce health inequalities. However, if policy makers are to achieve more rapid reductions in the NCD burden and health inequalities, they will also need to complement tobacco tax increases with additional tobacco control interventions focused on cessation.
Abstract 3275: Renoprotective Effect of Fish-Oil Supplement in Patients with Type II Diabetes
Authors: Ching Y Wong, Kai H Yiu, Leonard S Li, Stephen W Lee, Raymond H Chan, Sidney Tam, Chu P Lau, Hung F Tse
Journal: Circulation (2008)

Introduction: Increased dietary fish-oil consumption is associated with a reduced risk of coronary heart events and has pronounced effects on dyslipidemia. However, the effects of fish-oil suppleme...
Abstract 95: Early Administration of Epinephrine During Closed-Chest Resuscitation Fails to Improve Return of Spontaneous Circulation or Short-Term Survival
Authors: Domenico M Taglieri, Iyad M Ayoub, Julieta D Kolarova, Sufen Wang, Jeejabai Radhakrishnan, Raul J Gazmuri
Journal: Circulation (2006)
Abstract 10265: Drug Eluting Balloon-PCI is an Alternative to Drug Eluting Stents in Patients with a High Risk of Bleeding Complications
Authors: Mariusz Zadura, Frank Szigat, Birger Wolff, Peter Szigat, Ronald Bittner, Barnaba Hejazin, Wolfgang Motz
Journal: Circulation (2011)

OBJECTIVES: Patients after DES treatment with a strong indication for oral anticoagulants due to mechanical prosthetic heart valve, atrial fibrillation, pulmonary embolism etc. are at high risk of ...
发热-咳嗽-咳痰-呼吸困难
Authors: 赵鸿卫
Journal: BMJ (2011)

患者女，53岁。主诉：发热、咳嗽42d，咳痰、呼吸困难20d。患者于2010年10月19日因发热、咳嗽就诊于当地村卫生所，于发病第2天、第4天在家静脉滴注左氧氟沙星0.2 g、炎琥宁80mg，每日1次。4d后发热不退，体温38℃左右，偶咳。至当地县医院内科门诊，加用静脉滴注阿奇霉素0.5 g、每日1次（当天未用药）治疗3d，热未退，干咳。转入市医院住院治疗5d，用药不详，发热仍不退，阵发性咳嗽，偶有白黏痰。又转入省级三甲医院住院治疗16 d，其间发热不退，咳痰增多，呈大量白黏痰，时有黄脓痰，或痰中带血丝;有时呈剧烈阵发性咳嗽，伴窒息感，经吸痰方能缓解；并出现呼吸困难渐加重，呈端坐呼吸，颜面紫绀，遂住入重症监护病房。
Renal transplantation
Authors: A. Lopez-Navidad
Journal: BMJ (2002)

All you need is cognitive behaviour therapy? Critical appraisal of evidence base must be understood and respectedEditor-The article by Holmes and the accompanying commentaries essentially aim to explore the evidence for the efficacy and effectiveness of the psychotherapies and how this should be applied in everyday clinical practice. 1It is ironic that the arguments against cognitive therapy include numerous instances of idiosyncratic use of research evidence.Firstly, for example, in his commentary Bolsover selects three studies to support his view that the evidence base for cognitive therapy is weak.We would challenge him to apply his arguments to the seven systematic reviews of cognitive therapy in the Cochrane Database and the Database of Abstracts of Reviews of Effectiveness. 2 Holmes and also Bolsover cite a single paper to suggest that cognitive therapy is less effective in the real world of clinical practice than in university based clinical trials.This caricature may have applied to some trials conducted 30 years ago but is irrelevant now.To give just two examples, recent trials of cognitive therapy for chronic depression specifically recruited individuals who were depressed despite adequate trials of pharmacotherapy and psychotherapy. 3Also, the Cochrane review of cognitive therapy for schizophrenia includes examples of "real world" interventions. 4 Holmes argues that leading cognitive therapists are starting to question aspects of their discipline.However, these critiques are quoted out of context; the criticisms actually refer to the need to adapt the basic cognitive model to enhance its effectiveness for other disorders.Far from being a weakness, the critical appraisal of cognitive therapy by its practitioners is an important reason why it has been systematically evaluated in such a wide range of conditions.We agree with Holmes that it is unhelpful to evaluate psychotherapies by using only the research methods applied to drug trials.If clinicians and researchers aspire to an evidence based health service, however, they must accept two challenges.First is the challenge of evaluating what they think they do.We look forward to the evidence base of the psychodynamic psychotherapies developing, to allow more valid comparisons between the different approaches.Until then there is no escaping the robust evidence that exists for the use of cognitive therapy across clinical conditions and settings and the fact that much of this research is clearly applicable to the NHS.The second challenge is for clinicians and commentators to understand and respect the critical appraisal of the evidence base.Regrettably, some of the contributors to this series of articles have failed in this.
Abstract 16242: Cytoglobin Regulates Blood Pressure and Vascular Function through Metabolism of Nitric Oxide in the Vascular Wall
Authors: XiaopingLiu, Mohamed AEl-Mahdy, Raed SIsmail, Tamer MAbdelghany, Le TThuy, NorifumiKawada, Jay LZweier
Journal: Circulation (2013)

Cytoglobin (Cygb) is a recently identified mammalian globin. The physiological function of Cygb remains uncertain. We hypothesize that Cygb mediates metabolism of vascular endothelium-derived nitric oxide (NO), leading to regulation of NO bioavailability and vascular tone. We have used C57BL Cygb knockout (Cygb-/-) and wild type (WT) mice to test this hypothesis. The blood pressure (BP) and the response of aorta to endothelium-derived or exogenous NO were tested using non-invasive tail cuff and wire Myograph, respectively. The rate of vascular NO metabolism, using an electrochemical method, and the expression of NO-soluble guanylate cyclase (sGC) pathway key proteins were studied. Mean arterial BP of Cygb-/- mice was lower than that of WT mice (Fig. A). The phenylephrine-precontracted aorta of Cygb-/- mice was more sensitive to both acetylcholine (ACh) and nitroprusside-induced relaxation (Fig. B). A marked shift to the left in the relaxation-response curve was observed in Cygb-/- aorta. The flux of NO di...
Abstract 18015: Short and Long-Term Outcome of Impedance-Guided Preemptive Therapy Provided to Prevent Heart Failure in the Course of Acute Myocardial Infarction
Authors: Michael Shochat, Avraham Shotan, Mark Kazatsker, Yaniv Levy, Aya Asif, David Blondheim, Simgha Meisel
Journal: Circulation (2011)

Background Patients sustaining acute myocardial infarction (AMI) frequently develop acute heart failure (AHF) during hospitalization. Currently, treatment is initiated after the appearance of signs of lung fluid overload. Ongoing monitoring of the status of lung fluid content (LFC) may enable the prediction of impending AHF. Aims We sought to find out whether non-invasive lung impedance (LI) guided preemptive treatment of AMI patients improves clinical outcomes. Methods LI was determined by new noninvasive method. We have shown that a decrease of 12-14% from normal LI value reflects the transition from interstitial to alveolar edema. In the present study we prospectively randomized 213 patients (2:1 ratio) admitted for first AMI with no history of chronic heart failure (CHF) or signs of heart failure at admission and whose LI decreased by &gt;12% to conventional therapy or LI-guided preemptive treatment. Results 142 patients were treated conventionally (Gr1) and 71 preemptively according to LI (Gr2). Groups were well matched. All Gr1 patients developed AHF. Treatment was begun only at symptom onset. In Gr2 LI-guided preemptive treatment was initiated at the asymptomatic stage of evolving AHF and halted its progression in 89% of patients. Unadjusted analysis has shown that hospital stay, 1-year re-hospitalization rate after discharge, 6-year occurrence of new CHF and survival rate were better in Gr2 patients (p&lt;0. 001). Adjustment for age, LVEF, maximal CK, diabetes, hypertension, hyperlipidemia, smoking, level of creatinine and hemoglobin at admission have shown that LI-guided preemptive treatment was associated with better clinical outcome. Length of hospital stay (OR=5.28, CI: 3.10-8.09, p&lt;0.0001), 1-year re-hospitalization rate (OR=3.62, CI:2.16-6.06, p&lt;0.001), 6-years occurrence of new CHF (OR=3.41, CI:1.26-7.47, p=0.002) and 6-years mortality (OR=3.19, CI:1.13-9.01, p=0.028) were lower in Gr2 than in Gr1. The major factors influencing clinical outcome were age, diabetes mellitus, LVEF &lt;30% and maximal CK (&gt;2216 mg/dl) (p&lt;0.001). Conclusion s LI-guided preemptive therapy prevents the occurrence of AHF in 89% of patients, and decreases hospital stay, recurrent admissions, evolution to CHF and mortality during follow-up.
Abstract 1548: Determinants of Excessive Daytime Sleepiness in Adults With Heart Failure
Authors: Barbara Riegel, Steven Sayers, Lee Goldberg, Terri Weaver, Claudine Jurkovitz, William Weintraub, Sheryl Potashnik, Desiree Fleck, Sarah Ratcliffe
Journal: Circulation (2009)

Adults with heart failure (HF) have multiple reasons to have excessive daytime sleepiness (EDS), which may impair their abilities to function effectively during the day. The purpose of this study w...
Microarray profiling is feasible using archived tissue from a Cooperative Group Clinical Trial: Results from a pilot study in CALGB 9342
Authors: L. N. Harris, C. Perou, Z. Szallasi, A. Eklund, S. Carter, F. You, G. Broadwater, L. Monovich, E. Winer, M. Erlander, M. Ellis
Journal: Journal of Clinical Oncology (2005)

545 Background: CALGB 9342 was designed to test the efficacy of paclitaxel in women with advanced breast cancer. Tissue blocks were collected to retrospectively assess single gene markers (Lin et al, ASCO 2004, Abstract # 9562). RNA profiling has been able to classify tumors into biologic subtypes: ER/PR positive, HER2 amplified and basal-like (ER/PR/HER2 negative) (Perou et al, Nature 2001). To assess the feasibility of performing RNA microarray from this archived material, a pilot study was performed to determine if tumor subtypes could be identified by gene expression profiles. Methods: Primary tumors diagnosed between 1990–97 from women with metastatic breast cancer enrolled on CALGB 9342 were selected. Thirty formalin fixed, paraffin-embedded (FFPE) tissue blocks were selected based on HER2 by FISH (Vysis Pathvysion.), estrogen and progesterone receptor status (from pathology report) to equally represent three categories of breast cancer: HER2 amplified, ER and/or PR positive, ER/PR/HER2 negative. 4 uM tissue sections were macrodissected, RNA was isolated, linearly amplified, hybridized to two microarray platforms (Custom Agilent 22K gene chip, Affymetrix X3P whole genome array) using appropriate labeling methods. Tumors were classified by gene expression pattern using intrinsic signature genes and the ability to predict biomarker status was subsequently determined. Results: Twenty-eight of 30 cases could be successfully amplified and hybridized for microarray profiling. Ten percent of Agilent arrays and 20% of Affymetrix arrays were of poor quality. Both Agilent Whole Genome Chip and the Affymetrix X3P array correctly classified 9/10 HER2 positive, 8/9 ER/PR positive and 9/9 triple negative cases. Neither poor quality nor misclassification could be explained by year of embedding of the primary tumor. Conclusions: Microarray profiling from archived, FFPE tissue from cooperative group clinical trials is able to correctly classify tumor subtypes in the majority of cases. This data suggests that microarray profiling from large cohorts of archived tissue may be feasible to search for gene expression patterns that predict outcome. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Arcturus Arcturus
Abstract 19320: The Presence and Extent of Right Ventricular Electroanatomic Scar (by CARTO System) Predict the Outcome of Patients With Right Ventricular Arrhythmias
Authors: Federico Migliore, Alessandro Zorzi, Maria Silvano, Michela Bevilacqua, Koji Fukuzawa, Martina Perrazzolo Marra, Alessio Marinelli, Loira Leoni, Cristina Basso, Gianfranco Buja, Gaetano Thiene, Sabino Iliceto, Domenico Corrado
Journal: Circulation (2010)
H pylori and C pneumoniae infections may account for most acute coronary syndromes
Authors: A. Aceti, G. Mazzacurati, A. Pennica, M. A Amendolea, B. Zechini, M. Trappolini, M. Puletti
Journal: BMJ (1996)

least, more than one symptom could be scored and perhaps more attention could be paid to the patients' experience of their illness,' including how they explain their illness and its course, what effect it has, how they feel about it, and what they expect of treatment (this is relatively easily done in an n of 1 trial).The n of 1 trial could indeed be used more in everyday clinical practice with good instruments, generic diaries, and a patient centred approach.