tbuckley/cabot-search huggingface dataset:
Involvement of the CEBP Gene Family in Four IGH@ Chromosomal Translocations in B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL).
Authors: Martin J.S. Dyer, Takashi Akasaka, Theodore Balasas, Lisa Russell, Kei-Ji Sugimoto, Aneela Majid, David G. Brown, Kelvin Cain, Jon C. Strefford, Christine J. Harrison, Reiner Siebert
Journal: Blood (2005)
Abstract 1884: Rosuvastatin Activates Circulating Stem and Progenitor Cells, Promotes Endogenous Tissue Regeneration, and Improves Central Hemodynamics in Patients With Chronic Heart Failure
Authors: Sandra Erbs, Ephraim B Beck, Axel Linke, Volker Adams, Robert Höllriegel, Stephan Gielen, Sven Möbius-Winkler, Rainer Hambrecht, Gerhard Schuler
Journal: Circulation (2007)

Endogenous regeneration is impaired in patients (pts) with chronic heart failure (CHF), which results in peripheral, but also central hemodynamic alterations. Statins are known to promote stem cell release and enhance phosphorylation of the survival kinase AKT, which is associated with an increased cardiomyocyte contractility. Therefore, the present study aimed to investigate the effects of rosuvastatin on number and function of stem and circulating progenitor cells (CPC), their contribution to tissue neovascularization, and its impact on endothelial function and central hemodynamics in pts with CHF. Methods: Forty-two pts with CHF (EF 30±1%; n=12 ischemic, and n=30 dilative cardiomyopathy) were randomized to 12 weeks (wks) of 40 mg rosuvastatin daily or placebo therapy (P) in a double-blind manner. At begin (B) and at 12 wks, the number of circulating CD34 + stem cells and CD34/KDR + CPCs was measured, functional capacity of CPCs was assessed by migration and matrigel assay, and capillary density of skeletal muscle (SM) was quantified. Muscular phosphorylation levels of AKT were determined. Flow-mediated dilatation (FMD) was measured by high-resolution ultrasound and ejection fraction (EF) assessed by echocardiography. Results: Rosuvastatin increased the number of CPCs by +132% (p&lt;0.05 vs P), improved their migratory capacity by +83% and their integrative capacity by +91% (p&lt;0.05 vs P), respectively. FMD recovered from +197±25 μm at B to +478±50 μm at 12 wks in the rosuvastatin group. The rosuvastatin-mediated increase in circulating CD34 + cells was closely correlated to the improvement in FMD (r=0.70, p&lt;0.01) and the augmentation in capillary density of SM (r=0.76, p&lt;0.01). Rosuvastatin enhanced muscular AKT phosphorylation 2.5fold, which was associated with a gain in EF by + 8±1% (p&lt;0.05 vs P). All parameters remained unchanged in the placebo group. Conclusion: In pts with CHF, rosuvastatin improves left-ventricular ejection fraction, promotes skeletal muscle neovascularization, and enhances endothelial function, partially through activation of circulating stem and progenitor cells. Therefore, rosuvastatin might be considered as a therapeutic strategy to induce endogenous tissue regeneration and improve central hemodynamics in CHF.
Myocardial gene transfer by selective pressure-regulated retroinfusion of coronary veins
Authors: Philip Raake, Georges von Degenfeld, Rabea Hinkel, Robert Vachenauer, Torleif Sandner, Sabrina Beller, Martin Andrees, Christian Kupatt, Gerhard Schuler, Peter Boekstegers
Journal: Journal of the American College of Cardiology (2004)
Is the maximal tolerated dose still the best primary endpoint? Analysis of 288 dose-seeking phase I trials
Authors: J. Bonneterre, A. Adenis, E. Dansin, C. Ferté, S. Clisant, N. Penel
Journal: Journal of Clinical Oncology (2009)

2513 Background: For decades, the phase-2-recommended dose (P2RD) depends on toxicity (especially ‘the maximal tolerated dose', MTD) experienced by patients enrolled in dose-escalating phase 1 trials. Recent studies suggest that this policy is not suitable for modern anti-cancer agents. Methods: We retrospectively studied288 recently (1997–2008) published phase-I-trials using the maximal tolerated dose (MTD) to define the P2RD. We analysed how the P2RD was actually defined and then identified the risk factors for failure to establish the P2RD. Results: Seventeen percent (37/288) of the trials failed to identify the P2RD: 13% of studies investigating cytotoxic agents, 23% of studies investigating molecular targeted therapies and 33% of studies investigating immunostimulant agents. The risk factors for this failure were: trials investigating immunostimulant agents (Relative risk (RR)=2.9 [1.1–8.0]) or molecular targeted therapy (RR=3.1 [1.6–6.0]), single-agent regimen (RR=2.5 [1.3–4.9]), dose increments using of Fibonacci-modified series (RR=3.0 [1.5–5.8]), other method of escalation than ‘classical 3+3’ (RR=4.9 [1.6–14.2]) and almost the absence of clear definition of the MTD (RR=10.7 [3.6–32.2]). Indeed, in 9% of these studies (26/288), the definition of the MTD was not clearly established. Moreover, in 17% of all studies (38/288), the authors had proposed alternative but not standardised definitions of the P2RD (13 different definitions). These alternative definitions of P2DR were used in 18% of studies investigating cytotoxic agents, in 19% of studies investigating immunostimulant agents and in 24% of studies investigating molecular targeted therapies. Conclusions: In studies investigating cytotoxic agents, the definition of the MTD needs to be clarified in its 3 dimensions: severity of toxicity, duration of toxicity and proportion of patients experiencing this toxicity. Nevertheless, this appears less relevant for studies investigating immunostimulant agents and molecular targeted therapies. We have to explore and standardise alternative definitions of the P2DR in the era of modern agents. [Table: see text]
City of Calgary Plan for Natural Disaster
Authors: L C ALLAN
Journal: JAMA (1963)

THE DETAILS OF A PLAN TO COPE WITH ANY NATURAL DISASTER IN THE CITY OF CALGARY OR SURROUNDING AREA ARE PRESENTED IN TERMS OF: (1) the method of alerting personnel, (2) the mobilization of hospital authorities, additional hospital personnel, Civil Defence volunteers and Emergency Service facilities to deal with large numbers of injured victims; and (3) arrangements for the collection, feeding, clothing and temporary rehousing of those rendered homeless and deprived of the basic essentials of life.
Abstract 13830: Imatinib in the Presence of Platelet-derived Growth Factor Inhibits Proliferation and Induces Apoptosis in Pulmonary Artery Smooth Muscle Cells from Patients with Idiopathic Pulmonary Arterial Hypertension
Authors: Kazufumi Nakamura, Satoshi Akagi, Hiromi Matsubara, Aiko Ogawa, Aya Miura, Daiji Miura, Nobuhiro Nishii, Satoshi Nagase, Kunihisa Kohno, Hiroshi Morita, Kengo F Kusano, Hiroshi Ito
Journal: Circulation (2010)

Background: Idiopathic pulmonary arterial hypertension (IPAH) is characterized by an inappropriate increase in pulmonary artery smooth muscle cells (PASMCs). We assessed the inhibitory effects of i...
Abstract 16312: T1-Mapping is Superior to T2-Weighted Cardiovascular Magnetic Resonance Imaging for the Detection of Acute Reversible Myocardial Injury
Authors: Vanessa M Ferreira, Stefan K Piechnik, Erica Dall'Armellina, Theodoros D Karamitsos, Jane M Francis, Robin P Choudhury, Matthias G Friedrich, Matthew D Robson, Stefan Neubauer
Journal: Circulation (2011)

Background: T2-weighted cardiovascular magnetic resonance (CMR) using short-TI inversion recovery (STIR) is widely used to assess acute myocardial injury, but can be limited by posterior wall signa...
VACSATC (Vaccine safety: attitudes, training and communication): Why such a project?
Authors: M J Alvarez-Pasquín, H Heijbel, J Yarwood, P Van Damme, None VACSATC partners
Journal: Eurosurveillance (2009)

The Vaccine safety: attitudes, training and communication (VACSATC) project was established in 2006 to study perceptions of immunisation and vaccine safety, to improve training of healthcare professionals on vaccine safety and to improve the availability of information on vaccine safety on the internet that adheres to good information practices. The three year project is funded by the European Commission's Directorate General for Health and Consumers and by the partners. The project complements the activities of the Vaccine Safety Net project and the Vaccine European New Integrated Collaboration Effort (VENICE) project.
Abstract 11367: Association between Outpatient Visits Following Hospital Discharge and Readmissions among Medicare Beneficiaries with Atrial Fibrillation
Authors: Mai Hubbard, Sloane Frost, Kimberly Siu, Nicole Quon, Dominick Esposito
Journal: Circulation (2012)

Introduction Beginning in 2013, the Centers for Medicare & Medicaid Services (CMS) will penalize hospitals for certain excessive 30-day readmission rates. While studies examine the relationship bet...
Abstract 15746: Novel Metabolic Biomarkers Predict Cardiovascular Mortality
Authors: Abtehale Al-Hussaini, Jaspal S Kooner, Chambers John
Journal: Circulation (2013)

Background: Cardiovascular disease (CVD) is the Leading cause of mortality worldwide. Traditional risk factors of CVD have modest predictive power and discrimination. New biomarkers for CVD prediction are urgently required. Hypothesis: We used 1H NMR metabonomic profiling of serum to identify novel biomarkers of CVD. METHODS: We investigated 9,179 men and women, recruited between 2002-2008, participating in the London Life Sciences Population (LOLIPOP) study. Participants were followed up for CVD mortality to July 2011 (mean 5.5 years per person) and were assessed for CVD risk factors, including smoking, body mass index, blood pressure, fasting glucose and lipid profile. 1H NMR metabonomic profiling was done on baseline serum sample by 12T Bruker spectrometer, with quantification of 44 fatty acid and low molecular weight markers. RESULTS: There were 161 CVD deaths. Traditional risk factors were higher in people with CVD death compared to survivors (Table, all P<0.001). Framingham risk scores were higher i...
Abstract 320: Simulation of Cardiac Arrhythmias in Hospitalized Patients to Measure and Improve Response Time
Authors: Melanie C Wright, Kyle W Dorsey, Robert DeLong, Ronda Decker, Anita Patterson, Kathryn McBroom, Christopher B Granger
Journal: Circulation (2012)

Introduction: Hospitals have limited means of assessing time to respond to in-hospital life-threatening cardiac arrhythmias. Metrics of time to recognition are lacking and effectiveness of remote monitoring is not well understood. We sought to determine whether it was feasible and valid to measure response time to arrhythmias by inserting simulated arrhythmias into ongoing in-hospital cardiac monitoring. Hypothesis: We hypothesized that monitoring personnel would perceive a simulated arrhythmia, placed in the slot of a patient, as real and respond as such. We hypothesized that, compared to on-unit local monitoring (of monitors in the care area by direct care nurses), off-unit remote monitoring (of a bank of monitors by technicians), requiring more communication steps, would result in slower response time from arrhythmia onset to nurse-in-room. Methods: We conducted 50 simulated life-threatening arrhythmias (Vfib or Vtach) at two hospitals. We measured time from start of simulated arrhythmia to nurse-in-room. We asked 40 nurses and 13 monitoring technicians whether they perceived the event to be “real” (not a simulation). We compared nurse-to-room times between 28 locally and 15 remotely-monitored patient arrhythmias using non-parametric Wilcoxon sum of ranks statistics. Results: The event was interpreted as real by 38 of 40 nurses and 11 of 13 remote technicians. Among a subset (30 nurses, 6 technicians), about one-third, in hindsight, recalled aspects of the rhythm or work environment that could have cued them that the event was not real. Average nurse-to-room time for locally monitored patients was 23 seconds, significantly faster (p = 0.0002) than the 58 seconds required for remotely monitored patients. Conclusions: This study provides preliminary evidence that arrhythmia simulators may be used to effectively measure recognition and response time to life-threatening cardiac arrhythmias. Careful implementation is required to ensure realism.
Abstract 52: Comparison of Serial Monophasic and Biphasic Shocks in Out-of-Hospital Cardiac Arrest
Authors: Dirk Mueller, Daniel Flaschar, Luise Schnitzer, Hans-Richard Arntz
Journal: Circulation (2006)

Survival rates in sudden cardiac death (SCD) depend on initially registered arrhythmia, ventricular fibrillation (VF) having the best prognosis. The optimal energy for defibrillation, discharge characteristic of shock, and time point for shock application in patients (pts) with a prolonged down time in out-of-hospital SCD is under discussion. Methods: Data from the 2-tiered Berlin EMS were analyzed. LP300 monophasic (MON) and LP500 biphasic (BI) defibrillators (Physio Control Corp.) were used by the 1st tier. Shock series of three consecutive shocks each (200, 200, 360J MON and 150, 200, 360J BI) followed by 360J shocks each were delivered if appropriate. The information on rhythm and voices being stored in the AED devices was manually reviewed. Rhythm analysis was performed immediately before and 5sec after each shock. Results: Of 1700 pts with SCD in in 447 (26%) the initial rhythm was VF. These pts received at least one shock by the AED (MON n=223, BI n=224). VF was terminated by BI vs. MON shocks in 7...
Abstract 182: Dosing Time of Angiotensin Converting Enzyme Inhibitor is Important for Protecting Organ Damage in Hypertension
Authors: Takeshi Tsujino, Mika Matsumoto, Yoshiro Naito, Yoshida Chikako, Kana Wakabayashi, Tsuyoshi Sakoda, Mitsumasa Ohyanagi, Tohru Masuyama
Journal: Circulation (2007)

Introduction: There is a difference in the pattern of the diurnal variations of the aortic and cardiac mRNA expression of renin-angiotensin system between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats. Angiotensin II-dependent upregulation of gene expression was enhanced only in the daytime in the aorta of SHR. Hypothesis: Dosing time of angiotensin converting enzyme inhibitor may influence its organ protective effect in genetic hypertension. Methods: 10-week-old stroke prone spontaneously hypertensive rats (SHR-SP) were kept in a room in which a 12-h light/12-h dark cycle was maintained [lights on at 7 a.m.; Zeitgeber time (ZT) 0]. They were divided into three groups: the control group(C group: n=28)was given vehicle the morning group (M group: n=23) was given captopril (30mg/kg) at ZT0 the evening group (E group: n=23) was given captopril (30mg/kg) at ZT12. After 1 week of treatment, ACE activities of heart and kidney were measured 6 hours after drug-administration (n=8 for each group). After 7 weeks of treatment, urinary protein excretion, creatinine clearance, and heart weight/body weight ratio (HW/BW, mg/g) were examined. Five rats for each group underwent long-term implantation of a device that telemetrically monitors blood pressure (BP). Results: Mean BP elevation and premature death were equally prevented in the M group and E group compared to the C group. BP was lower in the day and higher in the night in the M group (day time BP vs. night time BP: 145.9 ± 10.3 vs. 163.7 ± 19.2 mmHg, p&lt;0.01), while BP was stable throughout a day in the E group (day time BP vs. night time BP: 152.2 ± 14.2 vs. 153.5 ± 14.7 mmHg, n.s.). After 1 week of treatment, cardiac and renal ACE activities were lower in the M group than in the E group (cardiac ACE activities: 0.639 ± 0.130 vs. 0.842 ± 0.085 nmol/mg tissue/hr, p&lt;0.01; renal ACE activities: 0.402 ± 0.145 vs. 0.728 ± 0.165 nmol/mg tissue/hr, p&lt;0.001). After 7 weeks of treatment, creatinine clearance was higher and HW/BW was lower in the M group than in the E group (2.93± 0.57 vs. 2.01± 0.43, p&lt;0.005; 4.33± 0.19 vs. 4.63 ± 0.36 g/kg, p&lt;0.05). Conclusions: Morning administration of captopril was more effective than evening one in terms of the strength of ACE inhibition and organ protection in SHR-SP.
Irish health board tackles waiting lists
Authors: Doug Payne
Journal: BMJ (2000)

The largest health board in the Republic of Ireland has launched an action plan to tackle waiting lists. Fifty three per cent of patients on Irish waiting lists are in the Eastern Regional Health Authority (ERHA), which includes Dublin.

Specialties with the longest waiting lists are orthopaedics; ear, nose, and throat; ophthalmology; plastic surgery, and vascular surgery. Overall, 40% of patients on lists have been waiting more than a year for …
Abstract 1756: Angiotensin II Induced End Organ Damage is Attenuated in Mice Lacking the Gene for TNF: A Mitochondrial Perspective
Authors: Nithya Mariappan, Srinivas Sriramula, Joseph Francis
Journal: Circulation (2008)

Recent findings from our lab and others suggest that the renin-angiotensin system and cytokine interaction contribute to the pathophysiology of cardiovascular disease. In this study, we determined the role played by tumor necrosis factor (TNF) in angiotensin II (ANGII) induced end organ damage at the mitochondrial level. Method : Wild type (WT) and TNF knockout (TNF (−/−)) mice were implanted with osmotic minipumps containing ANG II (1 μg/kg/min) or saline for 14 days. Blood pressure was recorded using telemetry. At the end of the study, left ventricular (LV) function was measured using echocardiography. Mice were sacrificed and the LV was removed and mitochondria isolated for oxidative stress measurement using Electron paramagnetic resonance spectroscopy. Structural integrity of mitochondria was assessed by electron microscopy (EM) and function by measuring mitochondrial redox status. Results: (see table ) ANGII infusion in WT mice resulted in a significant increase in blood pressure and was accompanied by a decrease in fractional shortening. These animals also had increased levels of superoxide and ROS in the LV tissues. The mitochondrial integrity of the cardiomyocytes was damaged both in the isolated mitochondria and tissue as evidenced by EM studies. Mitochondrial superoxide and total ROS were increased and this was accompanied by a decrease in complex activity and reduced ATP production. In contrast, ANGII infusion in TNF (−/−) attenuated cardiac damage, mitochondrial oxidative stress and restored ATP production. Conclusion: ANGII induced cardiac damage is mediated by TNF. These data also demonstrate that ANGII induced increase in TNF inhibits mitochondrial function by affecting electron transport chain activity and indirectly through an increase in oxygen free radicals thereby decreasing ATP synthesis and contributing to end organ damage in hypertension.
Abstract 1689: HDL Size and HDL Particle Concentration Independently Predict Coronary Artery Disease Risk in Apparently Healthy Individuals. The EPIC-Norfolk Prospective Population Study
Authors: Karim El Harchaoui, Benoit J Arsenault, Remco Franssen, Jean-Pierre Despres, G. Kees Hovingh, Erik S Stroes, James D Otvos, Nicholas Wareham, John J Kastelein, Kay-Tee Khaw, Matthijs S Boekholdt
Journal: Circulation (2008)
Abstract 194: A Combination of Metabolic Strategies and Cardiopulmonary Bypass Allows Improved Short-Term Resuscitation from Prolonged Lethal Cardiac Arrest
Authors: Manuel Boller, Sung K Jung, Silje Odegaard, Joseph M Katz, Amy Muehlmatt, Lance B Becker
Journal: Circulation (2011)

Background: The metabolic or late phase of cardiac arrest is highly lethal. Emergency cardiopulmonary bypass (ECPB) can resuscitate many patients even after prolonged cardiac arrest and provides immediate vascular access for correction of metabolic derangement during the reperfusion process. We developed a rodent model of ECPB resuscitation which showed the superiority of ECPB over conventional CPR, especially when combined with hypothermia. For this study we examined a metabolic strategy against ischemia/reperfusion (MS-I/R) injury that included: leukoreduction, low Ca2+, Mg, buffered pH, red blood cells and a colloid. We tested whether ECPB plus MS-I/R and/or hypothermia reduced reperfusion injury and showed better outcomes compared to our standard ECPB reperfusate. Methods: Using a 2x2 factorial design we tested ECPB with (a) MS-I/R versus standard solution, and (b) hypothermia versus normothermia in our rat model (n=38). The four reperfusion strategies included: (1) MS-I/R reperfusate plus hypothermia, (2) MS-I/R with normothermia, (3) standard plasmalyte reperfusate plus hypothermia, or (4) plasmalyte plus normothermia. Animals underwent 12 min of untreated asphyxial arrest and were resuscitated with ECPB with one of the strategies for 30 min. Thereafter ECPB was stopped and ICU-like support was provided for 3 hours, while hemodynamic, perfusion and other metrics were serially measured. Results: All rats achieved ROSC with ECPB. Significant differences emerged after 3 hrs, the best outcomes were in animals with MS-I/R perfusate plus hypothermia (lactate: 1.0±0.3 mmol/L; MAP: 84±12 mm Hg, seizures: 0/10), while the worst outcomes were with standard plasmalyte reperfusate and normothermia (lactate: 8.8±4.3 mmol/L, MAP: 36±13 mm Hg, seizures: 7/10, P&lt;0.001). The outcomes of the other two groups (hypothermia only; MS-I/R reperfusate only) were intermediate. Both hypothermia and MS-I/R reperfusate independently improved outcome. Conclusions: While most human ECPB is applied without a MS-I/R reperfusate, we observed that in rodents the addition of a MS-I/R reperfusate plus hypothermia to ECPB resuscitation resulted in short-term benefit after prolonged arrest. Future long-term and translational survival studies are warranted.
Abstract 17108: Exercised-Induced eNOS-NO Modulation of Microvascular Permeability in Mouse Hindlimb by MicroCT Imaging
Authors: Zhen W Zhuang, Michael Simons, Albert J Sinusas
Journal: Circulation (2011)

Introduction: There are controversies as to whether eNOS-derived NO functions as a permeability-increasing or -decreasing factor. These disputes might result from a lack of in vivo imaging system to monitor the dynamic changes of permeability. We hypothesized that microCT (μ CT) imaging would enable noninvasive in vivo spatial, temporal, and quantitative monitoring of permeability in the hindlimb. Methods: To test this hypothesis, we longitudinally monitored micro-molecular leakage in hindlimb ischemic (HLI) models of wild-type (WT, n=12) and eNOS −/− mice (n=12) at rest [sedentary (SED)] or with physiological stimulation [swimming (SW) training] on day 3 and 14. The same animals were subsequently evaluated by specimen μ CT with 20% Bismuth gelatin as a contrast agent for arteriogenesis and macromolecular leakage. Blood flow was assessed by laser Doppler Imaging in another group of mice (n=8/group). Immunohistochemical staining for capillary density was performed in additional mice (n = 4/group). Result: eNOS deficiency altered the pattern of microvascular permeability in the hindlimb. On day 3 in vivo μ CT showed WT-HLI-SED mice had a marked increase of late contrast enhancement (20 min) in the calf region. Swimming training reduced severity. In contrast, eNOS -/- -HLI-SED mice exhibited late enhancement at the site of pre-existing collaterals. Swimming resulted in a large area of increased permeability in the upper calf region. On day 14, eNOS -/- mice showed a shift of extravasation from the thigh to the calf and worsened after swimming compared to remarked recovery in WT mice. Moreover specimen μ CT demonstrated eNOS deletion resulted in bismuth particles leaking outside the vasculature in eNOS-HLI-SED mice and more serious in eNOS-HLI-SW mice while WT mice kept their vascular integrity on day 14. This enhanced leakage in eNOS -/- -HLI-SW mice was associated with decreased angiogenesis and dysfunctional arteriogenesis (increased arterioles with less perfusion). Conclusion: μ CT allowed longitudinally spatial and quantitative monitoring of in vivo permeability in model of murine hindlimb ischemia, and predicted matured arteriogenesis with exercise training and is eNOS-NO dependent.