tbuckley/cabot-search huggingface dataset:
Mechanical Dyssynchrony After Myocardial Infarction in Patients With Left Ventricular Dysfunction, Heart Failure, or Both
Authors: Sung-Hee Shin, Chung-Lieh Hung, Hajime Uno, Amira H. Hassanein, Anil Verma, Mikhail Bourgoun, Lars Køber, Jalal K. Ghali, Eric J. Velazquez, Robert M. Califf, Marc A. Pfeffer, Scott D. Solomon
Journal: Circulation (2010)

Background— Mechanical dyssynchrony is considered an independent predictor for adverse cardiovascular outcomes in patients with heart failure. However, its importance as a risk factor after myocardial infarction is not well defined. Methods and Results— We examined the influence of mechanical dyssynchrony on outcome in patients with left ventricular dysfunction, heart failure, or both after myocardial infarction who were enrolled in the Valsartan in Acute Myocardial Infarction (VALIANT) echocardiography study. B-mode speckle tracking with velocity vector imaging was used to assess ventricular synchrony in 381 patients who had image quality sufficient for analysis. Time to regional peak velocity and time to strain rate were measured among 12 left ventricular segments from the apical 4- and 2- chamber views, and the SDs between all 12 segments were used as a measure of dyssynchrony. The relationships between the SD of time to regional peak velocity and strain rate and clinical outcome of death or heart failure were assessed. In a multivariate Cox model adjusted for clinical and echocardiographic variables, the SD of time to peak velocity (hazard ratio per 10 ms, 1.10; 95% confidence interval, 1.02 to 1.18; P =0.010) and the SD of time to strain rate (hazard ratio per 10 ms, 1.16; 95% confidence interval, 1.06 to 1.27; P =0.001) were independent predictors of death or heart failure. Conclusion— Left ventricular dyssynchrony is independently associated with increased risk of death or heart failure after myocardial infarction, suggesting that contractile pattern may play a role in post–myocardial infarction prognosis.
Urine Detection of Survivin and Diagnosis of Bladder Cancer
Authors: S D Smith, M A Wheeler, J Plescia, J W Colberg, R M Weiss, D C Altieri
Journal: JAMA (2001)

Dysregulation of apoptosis may favor onset and progression of cancer and influence response to therapy. Survivin is an inhibitor of apoptosis that is selectively overexpressed in common human cancers, but not in normal tissues, and that correlates with aggressive disease and unfavorable outcomes.To investigate the potential suitability of survivin detection in urine as a novel predictive/prognostic molecular marker of bladder cancer.Survey of urine specimens from 5 groups: healthy volunteers (n = 17) and patients with nonneoplastic urinary tract disease (n = 30), genitourinary cancer (n = 30), new-onset or recurrent bladder cancer (n = 46), or treated bladder cancer (n = 35), recruited from 2 New England urology clinics.Detectable survivin levels, analyzed by a novel detection system and confirmed by Western blot and reverse transcriptase polymerase chain reaction (RT-PCR), in urine samples of the 5 participant groups.Survivin was detected in the urine samples of all 46 patients with new or recurrent bladder cancer using a novel detection system (31 of 31) and RT-PCR (15 of 15) methods. Survivin was not detected in the urine samples of 32 of 35 patients treated for bladder cancer and having negative cystoscopy results. None of the healthy volunteers or patients with prostate, kidney, vaginal, or cervical cancer had detectable survivin in urine samples. Of the 30 patients with nonneoplastic urinary tract disease, survivin was detected in 3 patients who had bladder abnormalities noted using cystoscopy and in 1 patient with an increased prostate-specific antigen level. Patients with low-grade bladder cancer had significantly lower urine survivin levels than patients with carcinoma in situ (P =.002).Highly sensitive and specific determination of urine survivin appears to provide a simple, noninvasive diagnostic test to identify patients with new or recurrent bladder cancer.
Re: Polymorphisms of Death Pathway Genes FAS and FASL in Esophageal Squamous-Cell Carcinoma
Authors: P. Krippl, U. Langsenlehner, W. Renner, H. Koppel, H. Samonigg
Journal: JNCI Journal of the National Cancer Institute (2004)

Re: Polymorphisms of Death Pathway Genes FAS and FASL in Esophageal Squamous-Cell CarcinomaWe have read with great interest the recent work by Sun et al.(1) about the role of functional FAS and FASL gene polymorphisms and esophageal squamouscell carcinoma risk.In addition to the report of Sun et al., polymorphisms of the FAS/FASL system have also been shown to be associated with acute myeloid leukemia (2), cervical cancer (3), and lung cancer (4).To analyze the role of FAS/FASL polymorphisms for breast cancer, we performed a case-control study that included 500 female breast cancer patients and 500 healthy sex-and age-matched control subjects.The study was approved by the Ethical Committee of the Medical University Graz.Written informed consent was obtained from all participating subjects.All subjects were Caucasian.FAS -1377GϾA, FAS -670AϾG, and FASL -844CϾT genotypes were determined by a 5Ј-nuclease assay (Taq-Man; Applera Austria Handels, Vienna, Austria).Primer and probe sets were designed and manufactured by the Applied Biosystems Assay-by-Design custom service (Applera Austria Handels).The following sequences of primers and probes were used to detect FAS and FASL polymorphisms: for FAS -1377GϾA, forward primer (5Ј-GCT CAGAGTGTGTGCACAAG-3Ј), reverse primer (5Ј-ACTGTTAGTGCCATGAG GAAGAC-3Ј), G-probe (5Ј-VIC-CTG GCACGCCCAGG-NFQ-3Ј, where VIC is the fluorescent dye, NFQ is the nonfluorescent quencher, and the underlined base indicates the polymorphic site), and A-probe (5Ј-FAM-CTGGCACAC CCAGG-NFQ-3Ј, where FAM is the fluorescent dye); for FAS -670AϾG, forward primer (5Ј-CTATGGCGCAA CATCTGTACTTTT-3Ј), reverse primer (5Ј-TCCATCTTGTGGCTGCAACAT-3Ј), G-probe (5Ј-VICCATTCCAG GAACGTC-NFQ-3Ј), and A-probe (5Ј-FAM-CATTCCAGAAACGTC-
Sleep-disordered Breathing and Prothrombotic Biomarkers
Authors: Reena Mehra, Fang Xu, Denise C. Babineau, Russell P. Tracy, Nancy S. Jenny, Sanjay R. Patel, Susan Redline
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Individuals with sleep-disordered breathing (SDB) are at increased cardiovascular risk, possibly due to SDB-related stresses contributing to atherosclerosis.
Magnetic Resonance Imaging Analysis of Right Ventricular Pressure-Volume Loops
Authors: Titus Kuehne, Sevim Yilmaz, Paul Steendijk, Phillip Moore, Maarten Groenink, Maythem Saaed, Oliver Weber, Charles B. Higgins, Peter Ewert, Eckard Fleck, Eike Nagel, Ingram Schulze-Neick, Peter Lange
Journal: Circulation (2004)

Background— The aims of this study were to validate MRI-derived right ventricular (RV) pressure-volume loops for assessment of RV myocardial contractility and then to apply this technique in patients with chronic RV pressure overload for assessment of myocardial contractility, ventricular pump function, and VA coupling. Methods and Results— Flow-directed catheters were guided under MR fluoroscopy (1.5 T) into the RV for invasive pressure measurements. Simultaneously, ventricular volumes and myocardial mass were assessed from cine MRI. From sampled data, RV pressure-volume loops were constructed, and maximal ventricular elastance indexed to myocardial mass (E max_i ) was derived by use of a single-beat estimation method. This MRI method was first validated in vivo (6 swine), with conductance techniques used as reference. Bland-Altman test showed good agreement between methods (E max_i =5.1±0.5 versus 5.8±0.7 mm Hg · mL −1 · 100 g −1 , respectively; P =0.08). Subsequently, the MRI method was applied in 12 subjects: 6 control subjects and 6 patients with chronic RV pressure overload from pulmonary hypertension. In these patients, indexes of RV pump function (cardiac index), E max_i , and VA coupling (E max /E a ) were assessed. In patients with pulmonary hypertension, RV pump function was decreased (cardiac index, 2.2±0.5 versus 2.9±0.4 L · min −1 · m −2 ; P &lt;0.01), myocardial contractility was enhanced (E max_I , 9.2±1.1 versus 5.0±0.9 mm Hg · mL −1 · 100 g −1 ; P &lt;0.01), and VA coupling was inefficient (E max /E a , 1.1±0.3 versus 1.9±0.4; P &lt;0.01) compared with control subjects. Conclusions— RV myocardial contractility can be determined from MRI-derived pressure-volume loops. Chronic RV pressure overload was associated with reduced RV pump function despite enhanced RV myocardial contractility. The proposed MRI approach is a promising tool to assess RV contractility in the clinical setting.
Higher Medical Care Costs Accompany Impaired Fasting Glucose
Authors: Gregory A. Nichols, Jonathan B. Brown
Journal: Diabetes Care (2005)

OBJECTIVE—The purpose of this study was to estimate medical costs associated with elevated fasting plasma glucose (FPG) and to determine whether costs differed for patients who met the 2003 (≥100 mg/dl) versus the 1997 (≥110 mg/dl) American Diabetes Association (ADA) cut point for impaired fasting glucose. RESEARCH DESIGN AND METHODS—We identified 28,335 patients with two or more FPG test results of at least 100 mg/dl between 1 January 1994 and 31 December 2003. Those with evidence of diabetes before the second test were excluded. We categorized patients into two stages of abnormal glucose (100–109 mg/dl and 110–125 mg/dl) and matched each of these subjects to a patient with a normal FPG test (&amp;lt;100 mg/dl) on age, sex, and year of FPG test. All subjects were followed until an FPG test qualified them for a higher stage, dispensing of an antihyperglycemic drug, health plan termination, or 31 December 2003. RESULTS—Adjusted annual costs were $4,357 among patients with normal FPG, $4,580 among stage 1 patients, and $4,960 among stage 2 patients (P &amp;lt; 0.001, all comparisons). After removing patients with normal FPG tests whose condition progressed to a higher stage or diabetes, costs in the normal FPG stage were $3,799. Patients in both stages 1 and 2 had more cardiovascular comorbidities than patients with normal FPG. CONCLUSIONS—Our results demonstrate that abnormal glucose metabolism is associated with higher medical care costs. Much of the excess cost was attributable to concurrent cardiovascular disease. The 2003 ADA cut point identifies a group of patients with greater costs and comorbidity than normoglycemic patients but with lower costs and less comorbidity than patients with FPG above the 1997 cut point.
Effect of Published Scientific Evidence on Glycemic Control in Adult Intensive Care Units
Authors: Daniel J. Niven, Gordon D. Rubenfeld, Andrew A. Kramer, Henry T. Stelfox
Journal: JAMA Internal Medicine (2015)

Little is known about the deadoption of ineffective or harmful clinical practices. A large clinical trial (the Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation [NICE-SUGAR] trial) demonstrated that strict blood glucose control (tight glycemic control) in patients admitted to adult intensive care units (ICUs) should be deadopted; however, it is unknown whether deadoption occurred and how it compared with the initial adoption.To evaluate glycemic control in critically ill patients before and after the publication of clinical trials that initially suggested that tight glycemic control reduced mortality (Leuven I) but subsequently demonstrated that it increased mortality (NICE-SUGAR).Interrupted time-series analysis of 353,464 patients admitted to 113 adult ICUs from January 1, 2001, through December 31, 2012, in the United States using data from the Acute Physiology and Chronic Health Evaluation database.The physiologically most extreme blood glucose level on day 1 of ICU admission defined glycemic control as tight control (glucose level, 80-110 mg/dL; to convert to millimoles per liter, multiply by 0.0555), hypoglycemia (glucose level, <70 mg/dL), and hyperglycemia (glucose level, ≥180 mg/dL). Temporal changes in each marker were examined using mixed-effects segmented linear regression.Before the publication of Leuven I, 17.2% (95% CI, 16.2%-18.2%) of ICU admissions had tight glycemic control, 3.0% (95% CI, 2.6%-3.5%) had hypoglycemia, and 40.2% (95% CI, 38.8%-41.5%) had hyperglycemia. After the publication of Leuven I, there were significant increases in the relative proportion of admissions with tight glycemic control (1.7% per quarter; 95% CI, 1.2%-2.3%; P<.001) and hypoglycemia (2.5% per quarter; 95% CI, 1.9%-3.2%; P<.001) and decreases in those with hyperglycemia (0.6% per quarter; 95% CI, 0.4%-0.9%; P<.001). Following the publication of NICE-SUGAR, there was no change in the proportion of patients with tight glycemic control or hyperglycemia. There was an immediate decrease in the relative proportion of patients with hypoglycemia (22.4%; 95% CI, 13.2%-30.1%; P<.001) but no subsequent change over time.Among patients admitted to adult ICUs in the United States, there was a slow steady adoption of tight glycemic control following publication of a clinical trial that suggested benefit, with little to no deadoption following a subsequent trial that demonstrated harm. There is an urgent need to understand and promote the deadoption of ineffective clinical practices.
Deregulated Expression of <i>EVI1</i> Defines a Poor Prognostic Subset of <i>MLL</i>-Rearranged Acute Myeloid Leukemias: A Study of the German-Austrian Acute Myeloid Leukemia Study Group and the Dutch-Belgian-Swiss HOVON/SAKK Cooperative Group
Authors: Stefan Gröschel, Richard F. Schlenk, Jan Engelmann, Veronika Rockova, Veronica Teleanu, Michael W.M. Kühn, Karina Eiwen, Claudia Erpelinck, Marije Havermans, Michael Lübbert, Ulrich Germing, Ingo G.H. Schmidt-Wolf, H. Berna Beverloo, Gerrit J. Schuurhuis, Gert J. Ossenkoppele, Brigitte Schlegelberger, Leo F. Verdonck, Edo Vellenga, Gregor Verhoef, Peter Vandenberghe, Thomas Pabst, Mario Bargetzi, Jürgen Krauter, Arnold Ganser, Peter J.M. Valk, Bob Löwenberg, Konstanze Döhner, Hartmut Döhner, Ruud Delwel
Journal: Journal of Clinical Oncology (2012)

To evaluate the prognostic value of ecotropic viral integration 1 gene (EVI1) overexpression in acute myeloid leukemia (AML) with MLL gene rearrangements.We identified 286 patients with AML with t(11q23) enrolled onto German-Austrian Acute Myeloid Leukemia Study Group and Dutch-Belgian-Swiss Hemato-Oncology Cooperative Group prospective treatment trials. Material was available from 177 AML patients for EVI1 expression analysis.We divided 286 MLL-rearranged AMLs into three subgroups: t(9;11)(p22;q23) (44.8%), t(6;11)(q27;q23) (14.7%), and t(v;11q23) (40.5%). EVI1 overexpression (EVI1(+)) was found in 45.8% of all patients with t(11q23), with t(6;11) showing the highest frequency (83.9%), followed by t(9;11) at 40.0%, and t(v;11q23) at 34.8%. Concurrent gene mutations were rare or absent in all three subgroups. Within all t(11q23) AMLs, EVI1(+) was the sole prognostic factor, predicting for inferior overall survival (OS; hazard ratio [HR], 2.06; P = .003), relapse-free survival (HR, 2.28; P = .002), and event-free survival (HR, 1.79; P = .009). EVI1(+) AMLs with t(11q23) in first complete remission (CR) had a significantly better outcome after allogeneic transplantation compared with other consolidation therapies (5-year OS, 54.7% v 0%; Mantel-Byar, P = .0006). EVI1(-) t(9;11) AMLs had lower WBC counts, more commonly FAB M5 morphology, and frequently had additional trisomy 8 (39.6%; P < .001). Among t(9;11) AMLs, EVI1(+) again was the sole independent adverse prognostic factor for survival.Deregulated EVI1 expression defines poor prognostic subsets among AML with t(11q23) and AML with t(9;11)(p22;q23). Patients with EVI1(+) MLL-rearranged AML seem to benefit from allogeneic transplantation in first CR.
Intravascular Adenovirus-Mediated VEGF-C Gene Transfer Reduces Neointima Formation in Balloon-Denuded Rabbit Aorta
Authors: Mikko O. Hiltunen, Marja Laitinen, Mikko P. Turunen, Michael Jeltsch, Juha Hartikainen, Tuomas T. Rissanen, Johanna Laukkanen, Mari Niemi, Maija Kossila, Tomi P. Häkkinen, Antti Kivelä, Berndt Enholm, Hannu Mansukoski, Anna-Mari Turunen, Kari Alitalo, Seppo Ylä-Herttuala
Journal: Circulation (2000)

Background —Gene transfer to the vessel wall may provide new possibilities for the treatment of vascular disorders, such as postangioplasty restenosis. In this study, we analyzed the effects of adenovirus-mediated vascular endothelial growth factor (VEGF)-C gene transfer on neointima formation after endothelial denudation in rabbits. For comparison, a second group was treated with VEGF-A adenovirus and a third group with lacZ adenovirus. Clinical-grade adenoviruses were used for the study. Methods and Results —Aortas of cholesterol-fed New Zealand White rabbits were balloon-denuded, and gene transfer was performed 3 days later. Animals were euthanized 2 and 4 weeks after the gene transfer, and intima/media ratio (I/M), histology, and cell proliferation were analyzed. Two weeks after the gene transfer, I/M in the lacZ -transfected control group was 0.57±0.04. VEGF-C gene transfer reduced I/M to 0.38±0.02 ( P &lt;0.05 versus lacZ group). I/M in VEGF-A–treated animals was 0.49±0.17 ( P =NS). The tendency that both VEGF groups had smaller I/M persisted at the 4-week time point, when the lacZ group had an I/M of 0.73±0.16, the VEGF-C group 0.44±0.14, and the VEGF-A group 0.63±0.21 ( P =NS). Expression of VEGF receptors 1, 2, and 3 was detected in the vessel wall by immunocytochemistry and in situ hybridization. As an additional control, the effect of adenovirus on cell proliferation was analyzed by performing gene transfer to intact aorta without endothelial denudation. No differences were seen in smooth muscle cell proliferation or I/M between lacZ adenovirus and 0.9% saline–treated animals. Conclusions —Adenovirus-mediated VEGF-C gene transfer may be useful for the treatment of postangioplasty restenosis and vessel wall thickening after vascular manipulations.
The Circadian Clock in the Kidney
Authors: Lisa R. Stow, Michelle L. Gumz
Journal: Journal of the American Society of Nephrology (2011)

Circadian variations in renal function were first described in the 19th century, and GFR, renal blood flow, urine production, and electrolyte excretion exhibit daily oscillations. These clinical observations are well established, but the underlying mechanisms that govern circadian fluctuations in kidney are not fully understood. Here we provide a brief overview of the machinery governing the circadian clock and examine the clinical and molecular evidence supporting a critical role for circadian rhythm in the kidney. There is a connection between BP oscillation and renal disease that supports the use of chronotherapy in the treatment of hypertension or correction of nondipping BP. Such studies support a developing model of clock controlled sodium and water transport in renal epithelial cells. Recent advances in identifying novel clock-controlled genes using rodent and cellular models also shed light on the molecular mechanisms by which the circadian clock controls renal function; however, the field is new and much more work remains.
Risk of ischaemic stroke in people with migraine: systematic review and meta-analysis of observational studies
Authors: Mahyar Etminan, Bahi Takkouche, Francisco Caamaño Isorna, Ali Samii
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To explore the association between migraine and risk of ischaemic stroke. <b>Design</b> Systematic review and meta-analysis. <b>Data sources</b> Observational studies published between 1966 and June 2004 (identified through Medline and Embase) that examined the association between migraine and risk of ischaemic stroke. <b>Results</b> 14 studies (11 case-control studies and 3 cohort studies) were identified. These studies suggest that the risk of stroke is increased in people with migraine (relative risk 2.16, 95% confidence interval 1.89 to 2.48). This increase in risk was consistent in people who had migraine with aura (relative risk 2.27, 1.61 to 3.19) and migraine without aura (relative risk 1.83, 1.06 to 3.15), as well as in those taking oral contraceptives (relative risk 8.72, 5.05 to 15.05). <b>Conclusions</b> Data from observational studies suggest that migraine may be a risk factor in developing stroke. More studies are needed to explore the mechanism of this potential association. In addition, the risk of migraine among users of oral contraceptives must be further investigated.
Survey of unlicensed and off label drug use in paediatric wards in European countries
Authors: S. Conroy
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To determine the extent of use of unlicensed and off label drugs in children in hospital in five European countries. <b>Design:</b> Prospective study of drugs administered to children in general paediatric medical wards over four weeks. <b>Setting:</b> Children9s wards in five hospitals (one each in the United Kingdom, Sweden, Germany, Italy, and the Netherlands). <b>Subjects:</b> Children aged 4 days to 16 years admitted to general paediatric medical wards. <b>Main outcome measure:</b> Proportion of drugs that were used in an unlicensed or off label manner. <b>Results:</b> 2262 drug prescriptions were administered to 624 children in the five hospitals. Almost half of all drug prescriptions (1036; 46%) were either unlicensed or off label. Of these 1036, 872 were off label and 164 were unlicensed. Over half of the patients (421; 67%) received an unlicensed or off label drug prescription. <b>Conclusions:</b> Use of off label or unlicensed drugs to treat children is widespread. This problem is likely to affect children throughout Europe and requires European action. <h3>Key messages</h3> Many drugs are not tested in children, which means that they are not specifically licensed for use in children Licensed drugs are often prescribed outside the terms of the product license (off label) in relation to age, indication, dose of frequency, route of administration, or formulation Over two thirds (67%) of 624 children admitted to wards in five European hospitals received drugs prescribed in an unlicensed or off label manner 39% of the 2262 drug prescriptions given to children were off label The problem of off label and unlicensed drug prescribing in children is a European problem that requires European action
Contribution of the basal ganglia to spoken language: Is speech production like the other motor skills?
Authors: Alexandre Zenon, Etienne Olivier
Journal: Behavioral and Brain Sciences (2014)

Abstract Two of the roles assigned to the basal ganglia in spoken language parallel very well their contribution to motor behaviour: (1) their role in sequence processing, resulting in syntax deficits, and (2) their role in movement “vigor,” leading to “hypokinetic dysarthria” or “hypophonia.” This is an additional example of how the motor system has served the emergence of high-level cognitive functions, such as language.
Mitochondrial Cardiomyopathy Evaluated With Cardiac Magnetic Resonance
Authors: Michio Nakanishi, Masaki Harada, Eiji Tadamura, Hirokazu Kotani, Rika Kawakami, Koichiro Kuwahara, Yasuaki Nakagawa, Satoru Usami, Hideyuki Kinoshita, Masataka Fujiwara, Kiminori Hosoda, Kenji Ueshima, Kazuwa Nakao
Journal: Circulation (2007)