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https://www.readbyqxmd.com/read/26670617/hydroxycarbamide-versus-chronic-transfusion-for-maintenance-of-transcranial-doppler-flow-velocities-in-children-with-sickle-cell-anaemia-tcd-with-transfusions-changing-to-hydroxyurea-twitch-a-multicentre-open-label-phase-3-non-inferiority-trial
#1
RANDOMIZED CONTROLLED TRIAL
Russell E Ware, Barry R Davis, William H Schultz, R Clark Brown, Banu Aygun, Sharada Sarnaik, Isaac Odame, Beng Fuh, Alex George, William Owen, Lori Luchtman-Jones, Zora R Rogers, Lee Hilliard, Cynthia Gauger, Connie Piccone, Margaret T Lee, Janet L Kwiatkowski, Sherron Jackson, Scott T Miller, Carla Roberts, Matthew M Heeney, Theodosia A Kalfa, Stephen Nelson, Hamayun Imran, Kerri Nottage, Ofelia Alvarez, Melissa Rhodes, Alexis A Thompson, Jennifer A Rothman, Kathleen J Helton, Donna Roberts, Jamie Coleman, Melanie J Bonner, Abdullah Kutlar, Niren Patel, John Wood, Linda Piller, Peng Wei, Judy Luden, Nicole A Mortier, Susan E Stuber, Naomi L C Luban, Alan R Cohen, Sara Pressel, Robert J Adams
BACKGROUND: For children with sickle cell anaemia and high transcranial doppler (TCD) flow velocities, regular blood transfusions can effectively prevent primary stroke, but must be continued indefinitely. The efficacy of hydroxycarbamide (hydroxyurea) in this setting is unknown; we performed the TWiTCH trial to compare hydroxyurea with standard transfusions. METHODS: TWiTCH was a multicentre, phase 3, randomised, open-label, non-inferiority trial done at 26 paediatric hospitals and health centres in the USA and Canada...
February 13, 2016: Lancet
https://www.readbyqxmd.com/read/26549714/isosorbide-mononitrate-in-heart-failure-with-preserved-ejection-fraction
#2
RANDOMIZED CONTROLLED TRIAL
Margaret M Redfield, Kevin J Anstrom, James A Levine, Gabe A Koepp, Barry A Borlaug, Horng H Chen, Martin M LeWinter, Susan M Joseph, Sanjiv J Shah, Marc J Semigran, G Michael Felker, Robert T Cole, Gordon R Reeves, Ryan J Tedford, W H Wilson Tang, Steven E McNulty, Eric J Velazquez, Monica R Shah, Eugene Braunwald
BACKGROUND: Nitrates are commonly prescribed to enhance activity tolerance in patients with heart failure and a preserved ejection fraction. We compared the effect of isosorbide mononitrate or placebo on daily activity in such patients. METHODS: In this multicenter, double-blind, crossover study, 110 patients with heart failure and a preserved ejection fraction were randomly assigned to a 6-week dose-escalation regimen of isosorbide mononitrate (from 30 mg to 60 mg to 120 mg once daily) or placebo, with subsequent crossover to the other group for 6 weeks...
December 10, 2015: New England Journal of Medicine
https://www.readbyqxmd.com/read/26354913/in-vivo-inhibition-of-mir-155-promotes-recovery-after-experimental-mouse-stroke
#3
Ernesto Caballero-Garrido, Juan Carlos Pena-Philippides, Tamar Lordkipanidze, Denis Bragin, Yirong Yang, Erik Barry Erhardt, Tamara Roitbak
A multifunctional microRNA, miR-155, has been recently recognized as an important modulator of numerous biological processes. In our previous in vitro studies, miR-155 was identified as a potential regulator of the endothelial morphogenesis. The present study demonstrates that in vivo inhibition of miR-155 supports cerebral vasculature after experimental stroke. Intravenous injections of a specific miR-155 inhibitor were initiated at 48 h after mouse distal middle cerebral artery occlusion (dMCAO). Microvasculature in peri-infarct area, infarct size, and animal functional recovery were assessed at 1, 2, and 3 weeks after dMCAO...
September 9, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/26239227/prolonged-diet-induced-obesity-in-mice-modifies-the-inflammatory-response-and-leads-to-worse-outcome-after-stroke
#4
COMPARATIVE STUDY
Samaneh Maysami, Michael J Haley, Natalia Gorenkova, Siddharth Krishnan, Barry W McColl, Catherine B Lawrence
BACKGROUND: Obesity increases the risk for ischaemic stroke and is associated with worse outcome clinically and experimentally. Most experimental studies have used genetic models of obesity. Here, a more clinically relevant model, diet-induced obesity, was used to study the impact of obesity over time on the outcome and inflammatory response after stroke. METHODS: Male C57BL/6 mice were maintained on a high-fat (60% fat) or control (12% fat) diet for 2, 3, 4 and 6 months when experimental stroke was induced by transient occlusion of the middle cerebral artery (MCAo) for either 20 (6-month diet) or 30 min (2-, 3-, 4- and 6-month diet)...
August 4, 2015: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/24498217/co-administration-of-resveratrol-and-lipoic-acid-or-their-synthetic-combination-enhances-neuroprotection-in-a-rat-model-of-ischemia-reperfusion
#5
Monique C Saleh, Barry J Connell, Desikan Rajagopal, Bobby V Khan, Alaa S Abd-El-Aziz, Inan Kucukkaya, Tarek M Saleh
The present study demonstrates the benefits of combinatorial antioxidant therapy in the treatment of ischemic stroke. Male Sprague-Dawley rats were anaesthetised and the middle cerebral artery (MCA) was occluded for 30 minutes followed by 5.5 hours of reperfusion. Pretreatment with resveratrol 30 minutes prior to MCA occlusion resulted in a significant, dose-dependent decrease in infarct volume (p<0.05) compared to vehicle-treated animals. Neuroprotection was also observed when resveratrol (2 × 10(-3) mg/kg; iv) was administered within 60 minutes following the return of blood flow (reperfusion)...
2014: PloS One
https://www.readbyqxmd.com/read/23899887/myocardial-dimensions-and-hemodynamics-during-24-h-ultraendurance-ergometry
#6
Rochus Pokan, Helmuth Ocenasek, Rainer Hochgatterer, Martin Miehl, Karin Vonbank, Serge P Von Duvillard, Barry Franklin, Sabine Würth, Ivo Volf, Manfred Wonisch, Peter Hofmann
PURPOSE: This study aimed to evaluate cardiorespiratory and hemodynamic responses during 24 h of continuous cycle ergometry in ultraendurance athletes. METHODS: Eight males (mean ± SD; age = 39 ± 8 yr, height = 179 ± 7 cm, body weight [Wt] = 77.1 ± 6.0 kg) were monitored during 24 h at a constant workload,∼25% below the first lactate turn point at 162 ± 23 W. Measurements included Wt, HR, oxygen consumption (V˙O2), cardiac output (Q), and stroke volume (SV) determined by a noninvasive rebreathing technique (Innocor; Innovision, Odense, Denmark)...
February 2014: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/23478662/effect-of-phosphodiesterase-5-inhibition-on-exercise-capacity-and-clinical-status-in-heart-failure-with-preserved-ejection-fraction-a-randomized-clinical-trial
#7
RANDOMIZED CONTROLLED TRIAL
Margaret M Redfield, Horng H Chen, Barry A Borlaug, Marc J Semigran, Kerry L Lee, Gregory Lewis, Martin M LeWinter, Jean L Rouleau, David A Bull, Douglas L Mann, Anita Deswal, Lynne W Stevenson, Michael M Givertz, Elizabeth O Ofili, Christopher M O'Connor, G Michael Felker, Steven R Goldsmith, Bradley A Bart, Steven E McNulty, Jenny C Ibarra, Grace Lin, Jae K Oh, Manesh R Patel, Raymond J Kim, Russell P Tracy, Eric J Velazquez, Kevin J Anstrom, Adrian F Hernandez, Alice M Mascette, Eugene Braunwald
IMPORTANCE: Studies in experimental and human heart failure suggest that phosphodiesterase-5 inhibitors may enhance cardiovascular function and thus exercise capacity in heart failure with preserved ejection fraction (HFPEF). OBJECTIVE: To determine the effect of the phosphodiesterase-5 inhibitor sildenafil compared with placebo on exercise capacity and clinical status in HFPEF. DESIGN: Multicenter, double-blind, placebo-controlled, parallel-group, randomized clinical trial of 216 stable outpatients with HF, ejection fraction ≥50%, elevated N-terminal brain-type natriuretic peptide or elevated invasively measured filling pressures, and reduced exercise capacity...
March 27, 2013: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/23178505/interaction-of-age-with-the-ischaemic-penumbra-leptomeningeal-collateral-circulation-and-haemodynamic-variables-in-acute-stroke-a-pilot-study
#8
Smriti Agarwal, Daniel J Scoffings, P Simon Jones, S Tulasi Marrapu, Patrick J Barry, Eoin W O'Brien, Jean-Claude Baron, Elizabeth A Warburton
BACKGROUND: Increasing age is the single largest non-modifiable risk factor for ischaemic stroke. Animal models have substantiated the view that age related neuron vulnerability to ischaemia plays a role in stroke and other age related neurological diseases. Given the key role of the ischaemic penumbra in stroke pathophysiology, we hypothesised that age has an impact on penumbral tissue and its acute determinants. METHODS: We studied a prospective cohort of patients (n=39) at a mean time of 154...
March 2013: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/23137508/biomarkers-in-acutely-decompensated-heart-failure-with-preserved-or-reduced-ejection-fraction
#9
RANDOMIZED CONTROLLED TRIAL
Kalkidan Bishu, Anita Deswal, Horng H Chen, Martin M LeWinter, Gregory D Lewis, Marc J Semigran, Barry A Borlaug, Steven McNulty, Adrian F Hernandez, Eugene Braunwald, Margaret M Redfield
BACKGROUND: Acute decompensated heart failure (ADHF) occurs with preserved (heart failure with preserved ejection fraction [HFpEF] ≥50%) or reduced (heart failure with reduced ejection fraction [HFrEF] <50%) ejection fraction. Natriuretic peptide (NP) levels are lower in HFpEF than HFrEF. We hypothesized that lower NP levels in HFpEF may be associated with other differences in biomarkers, specifically, renin-angiotensin-aldosterone system (RAAS) activation, oxidative stress, and a biomarker that reflects collagen synthesis...
November 2012: American Heart Journal
https://www.readbyqxmd.com/read/22995799/blood-pressure-and-treatment-of-persons-with-hypertension-as-it-relates-to-cognitive-outcomes-including-executive-function
#10
REVIEW
Philip B Gorelick, David Nyenhuis, Barry J Materson, David A Calhoun, William J Elliott, Robert A Phillips, Sandra J Taler, Raymond R Townsend
No abstract text is available yet for this article.
September 2012: Journal of the American Society of Hypertension: JASH
https://www.readbyqxmd.com/read/22781338/delayed-administration-of-interleukin-1-receptor-antagonist-reduces-ischemic-brain-damage-and-inflammation-in-comorbid-rats
#11
Jesus M Pradillo, Adam Denes, Andrew D Greenhalgh, Herve Boutin, Caroline Drake, Barry W McColl, Eleanor Barton, Spencer D Proctor, James C Russell, Nancy J Rothwell, Stuart M Allan
Many neuroprotective agents have been effective in experimental stroke, yet few have translated into clinical application. One reason for this may be failure to consider clinical comorbidities/risk factors in experimental models. We have shown that a naturally occurring interleukin-1 receptor antagonist (IL-1Ra) is protective against ischemic brain damage in healthy animals. However, protective effects of IL-1Ra have not been determined in comorbid animals. Thus, we tested whether IL-1Ra protects against brain injury induced by experimental ischemia in aged JCR-LA (corpulent) rats, which have clinically relevant risk factors...
September 2012: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/21860235/does-perfusion-computed-tomography-facilitate-clinical-decision-making-for-thrombolysis-in-unselected-acute-patients-with-suspected-ischaemic-stroke
#12
S Agarwal, P S Jones, J A Alawneh, N M Antoun, P J Barry, E Carrera, P E Cotter, E W O'Brien, I Salih, D J Scoffings, J-C Baron, E A Warburton
BACKGROUND: Despite use in clinical practice and major positive trials of thrombolysis, non-contrast computed tomography (NCCT) is not sensitive for identifying penumbral tissue in acute stroke. This study evaluated how physiological imaging using CT perfusion (CTP) could add to the diagnostic utility of an NCCT and inform clinical decisions regarding thrombolysis. METHODS: Forty imaging datasets containing NCCT and CTP were retrospectively identified from a cohort of consecutive acute stroke patients...
2011: Cerebrovascular Diseases
https://www.readbyqxmd.com/read/21700941/oxidative-damage-in-ischemic-stroke-revealed-using-multiple-biomarkers
#13
Raymond C S Seet, Chung-Yung J Lee, Bernard P L Chan, Vijay K Sharma, Hock-Luen Teoh, Narayanaswamy Venketasubramanian, Erle C H Lim, Wan-Ling Chong, Woan-Foon Looi, Shan-Hong Huang, Benjamin K C Ong, Barry Halliwell
BACKGROUND AND PURPOSE: We investigated changes in oxidative damage after ischemic stroke using multiple biomarkers. METHODS: Serial blood and urine samples of ischemic stroke subjects and age-matched control subjects were assayed for F₂-isoprostanes, hydroxyeicosatetraenoic acid products, F₄-neuroprostanes, 24-hydroxycholesterol, allantoin, and urate. RESULTS: Sixty-six stroke subjects (mean age, 65 years; median National Institutes of Health Stroke Scale 17) and 132 control subjects were recruited...
August 2011: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/21559030/stroke-penumbra-defined-by-an-mri-based-oxygen-challenge-technique-2-validation-based-on-the-consequences-of-reperfusion
#14
Craig A Robertson, Christopher McCabe, Lindsay Gallagher, Maria del Rosario Lopez-Gonzalez, William M Holmes, Barrie Condon, Keith W Muir, Celestine Santosh, I Mhairi Macrae
Magnetic resonance imaging (MRI) with oxygen challenge (T(2)(*) OC) uses oxygen as a metabolic biotracer to define penumbral tissue based on CMRO(2) and oxygen extraction fraction. Penumbra displays a greater T(2)(*) signal change during OC than surrounding tissue. Since timely restoration of cerebral blood flow (CBF) should salvage penumbra, T(2)(*) OC was tested by examining the consequences of reperfusion on T(2)(*) OC-defined penumbra. Transient ischemia (109 ± 20 minutes) was induced in male Sprague-Dawley rats (n=8)...
August 2011: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/21377453/characterizing-the-role-of-the-neuropeptide-substance-p-in-experimental-subarachnoid-hemorrhage
#15
Christine M Barry, Stephen C Helps, Corinna van den Heuvel, Robert Vink
BACKGROUND: Raised intracranial pressure (ICP) following SAH predicts poor outcome and is due to hemorrhage volume and possibly, brain edema, hydrocephalus and increased volume of circulating intracranial blood. Interventions that reduce edema may therefore reduce ICP and improve outcome. The neuropeptide substance P (SP) mediates vasogenic edema formation in animal models of ischemic stroke, intracerebral hemorrhage and brain trauma, and may contribute to development of increased ICP...
May 10, 2011: Brain Research
https://www.readbyqxmd.com/read/21172313/lipoic-acid-protects-against-reperfusion-injury-in-the-early-stages-of-cerebral-ischemia
#16
Barry J Connell, Monique Saleh, Bobby V Khan, Tarek M Saleh
Lipoic acid (LA) is a known antioxidant currently used as a therapy in patients with vascular and metabolic disorders. We tested the hypothesis that lipoic acid is protective against the cell death observed following stroke. Lipoic acid was administered 30minutes prior to, or immediately following removal of sutures used to occlude the middle cerebral artery (MCA) in male Sprague-Dawley rats. Following removal of the sutures, the MCA territory was allowed to undergo 5.5hrs of reperfusion. This ischemia/reperfusion (I/R) resulted in a focal infarct restricted to the prefrontal cortex (24±3mm(3))...
February 23, 2011: Brain Research
https://www.readbyqxmd.com/read/20437554/randomized-controlled-trial-of-insulin-for-acute-poststroke-hyperglycemia
#17
RANDOMIZED CONTROLLED TRIAL
Michael McCormick, Donald Hadley, John R McLean, Jennifer A Macfarlane, Barrie Condon, Keith W Muir
OBJECTIVE: Poststroke hyperglycemia is common and is associated with increased risk of death and dependence, but appropriate management remains uncertain. Glucose potassium insulin (GKI) infusion did not benefit patients with moderate poststroke hyperglycemia in a recent trial. Using magnetic resonance imaging (MRI), previous studies identified a relationship between recruitment of ischemic tissue to the final infarct and hyperglycemia, possibly mediated by brain lactic acidosis. METHODS: We undertook a randomized, placebo-controlled trial of GKI infusion in patients with blood glucose >126mg/dl (7mmol/l) within 24 hours of ischemic stroke...
May 2010: Annals of Neurology
https://www.readbyqxmd.com/read/20299607/randomized-double-blind-multicenter-placebo-controlled-study-evaluating-the-effect-of-aldosterone-antagonism-with-eplerenone-on-ventricular-remodeling-in-patients-with-mild-to-moderate-heart-failure-and-left-ventricular-systolic-dysfunction
#18
RANDOMIZED CONTROLLED TRIAL
James E Udelson, Arthur M Feldman, Barry Greenberg, Bertram Pitt, Robin Mukherjee, Henry A Solomon, Marvin A Konstam
BACKGROUND: Aldosterone antagonism has been studied in patients with advanced heart failure (HF) and also in patients with post-myocardial infarction and left ventricular (LV) dysfunction with HF symptoms. Few data are available on effects of aldosterone antagonism in patients with mild-to-moderate HF. METHODS AND RESULTS: In a multicenter, randomized, double-blind, placebo-controlled study in patients with mild-to-moderate HF and LV systolic dysfunction, patients with New York Heart Association class II/III HF and LV ejection fraction (EF) < or =35% were randomly assigned to receive eplerenone 50 mg/d versus placebo in addition to contemporary background therapy...
May 2010: Circulation. Heart Failure
https://www.readbyqxmd.com/read/20150567/acute-cardiac-effects-of-marathon-running
#19
Justin E Trivax, Barry A Franklin, James A Goldstein, Kavitha M Chinnaiyan, Michael J Gallagher, Adam T deJong, James M Colar, David E Haines, Peter A McCullough
We sought to clarify the significance of cardiac dysfunction and to assess its relationship with elevated biomarkers by using cardiovascular magnetic resonance imaging in healthy, middle-aged subjects immediately after they ran 26.2 miles. Cardiac dysfunction and elevated blood markers of myocardial injury have been reported after prolonged strenuous exercise. From 425 volunteers, 13 women and 12 men were randomly selected, provided medical and training history, and underwent baseline cardiopulmonary exercise testing to exhaustion...
May 2010: Journal of Applied Physiology
https://www.readbyqxmd.com/read/19826431/increased-brain-microvascular-mmp-9-and-incidence-of-haemorrhagic-transformation-in-obese-mice-after-experimental-stroke
#20
Barry W McColl, Nicola Rose, Fiona H Robson, Nancy J Rothwell, Catherine B Lawrence
Obesity is an independent risk factor for stroke and is associated with poorer outcome after stroke. We investigated whether this poorer outcome is related to brain microvascular disruption. Focal cerebral ischaemia was induced in lean or obese (ob/ob) mice by transient middle cerebral artery occlusion. The incidence of haemorrhagic transformation and the volume of ischaemic brain damage were significantly greater in obese mice. Blood-brain barrier permeability and brain microvascular MMP-9 expression were also markedly increased in obese mice...
February 2010: Journal of Cerebral Blood Flow and Metabolism
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