tbuckley/cabot-search huggingface dataset:
Hospital criticised for not obtaining “properly elicited consent”
Authors: Adam Legge
Journal: BMJ (2000)

Tighter controls on clinical research in the NHS are to be introduced by the government in response to a highly critical review of a study carried out at North Staffordshire Hospital NHS Trust.

The review has raised serious concerns over the issue of consent for a trial on neonates with respiratory failure run by Professor David Southall, consultant paediatrician at the hospital. The randomised controlled trial looked at the effect of treating premature babies with continuous negative extrathoracic pressure (CNEP) ventilation instead of standard ventilation. The results showed improved respiratory outcomes with the new method but an increase (which was not statistically significant) in baby deaths ( Pediatrics 1996;98:1154-1160).

The review's author is Professor Rod Griffiths, director of public health at the …
Abstract 1870: Pathophysiology of Chronic Venous Insufficiency in the Adult With a Fontan Circulation
Authors: Ami B Bhatt, Marie D Gerhard-Herman, Elizabeth Rodriguez-Huertas, Dionne A Graham, Michael J Landzberg, Anne M Valente
Journal: Circulation (2009)

INTRODUCTION: Chronic venous insufficiency (CVI) is prevalent in adults with a Fontan circulation, however the pathophysiology is unknown. We defined the prevalence of venous reflux and obstruction...
Limitation of Angiography to Identify the Culprit Plaque in Acute Myocardial Infarction With Coronary Total Occlusion
Authors: Takuro Takumi, Souki Lee, Shuichi Hamasaki, Kouichi Toyonaga, Daisuke Kanda, Keisuke Kusumoto, Hitoshi Toda, Toshihiro Takenaka, Masaaki Miyata, Ryuichiro Anan, Yutaka Otsuji, Chuwa Tei
Journal: Journal of the American College of Cardiology (2007)
A preclinical study of cellular immunotherapy redirected by bispecific antibodies in uterine cell lines and primary cancer cells
Authors: C. A. Hamilton, M. M. Zhang, J. K. Chan, M. K. Cheung, S. H. Thorne, J. Baker, C. H. Contag, R. S. Negrin
Journal: Journal of Clinical Oncology (2006)

15044 Background: Cytokine induced killer cells (CIKs) are ex-vivo activated and expanded CD8+ natural killer T cells that have been shown to have cytotoxic activity against cancers in randomized clinical trials. We determined the cytotoxic activity of CIK cells against endometrioid and serous papillary (UPSC) uterine cancer cell lines and evaluated the ability of Trastuzumab and Her2xCD3 bispecific antibodies to enhance CIK-mediated cytotoxicity in Her2/neu expressing uterine cancer cells. Methods: The cytotoxicity of CIKs was quantified by 4-hour 51Cr release assays against uterine cell lines HEC-1A (endometrioid) and SPEC-2 (UPSC). Bispecific antibodies against Her2/neu (BSAbHer2) were designed using chemical conjugation methods. Results: Using FACS analysis, we found that the population of CD3+ CD8+ T cells increased from 24% to 56% over 21 days, while the CD3+ CD56+ T cells increased from 7% to 14%. Immunofluorescence microscopy revealed that both cell lines overexpressed Her2/neu. Cytotoxicity assays were performed at effector to target (E:T) ratios of 10:1, 20:1, 40:1 and 100:1 with increasing E:T ratio correlating directly with mean percent specific lysis. At the 100:1 E:T ratio, the mean percent lysis of CIKs against HEC-1A and SPEC-2 cells was 38.8% (±0.21) and 35% (±3.4), respectively. Trastuzumab did not affect the cytotoxic activity of CIKs. However, BSAbHer2 redirection significantly enhanced the cytotoxicity of CIKs against HEC-1A and SPEC-2 cells with a mean percent lysis of 66.3% (±1.0) and 50% (±2.7), respectively. Anti-NKG2D antibodies significantly reduced CIK activity by 49% and 47% in HEC-1A and SPEC-2 cells, respectively. The effects of CIK on advanced uterine cancers were demonstrated using our in vivo bioluminescence imaging system. Conclusion: CIK cells have cytotoxic activity both endometriod and UPSC cell lines. Redirection by BSAbHer2 significantly increased CIK-cell mediated cytotoxicity against Her2/neu expressing cell lines. The mechanism of CIK cytotoxicity appears to be partly mediated by the NKG2D receptor. No significant financial relationships to disclose.
Abstract 16589: IK,ATP Gain-of-Function Decreases Transmural Ventricular Dispersion of Repolarization While Increasing Dispersion Between Chambers
Authors: Jonathan R Silva, Hai Xia Zhang, John W Verbsky, Urvi S Lee, Evelyn M Kanter, Kathryn A Yamada, Richard B Schuessler, Colin G Nichols
Journal: Circulation (2011)

Gain-of-function mutations in channel subunits responsible for the ATP-sensitive K+ current,IK,ATP, have recently been identified in patients with Early Repolarization Syndrome, which predisposes t...
Screening with Ultrasonography of Patients at High-Risk for Hepatocellular Carcinoma: Thrombocytopenia as a Valid Surrogate of Cirrhosis
Authors: Sheng-Nan Lu, Jing-Houng Wang, Kwong-Ming Kee, Po-Lin Tseng
Journal: Liver Cancer (2009)

Sequelae of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, including hepatocellular carcinoma (HCC), liver cirrhosis (LC) and their complications, are health burdens of the world. Improving treatment results for early stage HCC makes the screening meaningful. Two-staged HCC screening identifying high risk subjects in the first stage and screening for HCC by ultrasonography (US) in the second stage is a practical and workable concept. The benefit of US screening on high risk groups has been well documented, but "who should be included in the US screening" depends on cost-benefits and considerations of feasibility.
Abstract 289: Complete 5 Year Follow-up of Coronary Artery Bypass Graft Patients Treated With Clopidogrel
Authors: Hartmuth B Bittner, Sven Lehmann, Ardawan Rastan, Janine Lemke, Michelle Lange, Friedhelm Mohr
Journal: Circulation (2010)

Objective: An increased number of patients undergoing OPCABG is preoperatively treated with irreversible platelet inhibitors such as Clopidogrel. The objective was to evaluate its impact on bleedin...
Abstract 12542: A Single-Dose Recombinant Glutathione S-Transferase P1-1 Improves Cardiac Function Post Myocardial Infarction in Rats
Authors: Seyedhossein Aharinejad, Mohamed Salama, Olena Andrukhova, Dominik Wiedemann, Martin Krssak, Lamia El-Housseiny, Alfred Kocher, Guenther Laufer
Journal: Circulation (2011)

Acute myocardial infarction (MI) is associated with inflammatory cascades that go on to harm cardiomyocytes even after the acute event. Cellular tumor necrosis factor (TNF)-α signaling occurs via T...
Abstract 9162: Echocardiographic Strain Imaging Allows Differentiation Between Heart Transplant Recipients with and Without Coronary Stenoses
Authors: Michael Dandel, Chol-Ho Pang, Ernst Wellnhofer, Christoph Knosalla, Roland Hetzer
Journal: Circulation (2011)

Background: Early detection of patients with cardiac allograft vasculopathy (CAV) is a major goal. However, because diffuse distal coronary narrowing is a major determinant of left ventricular (LV) dysfunction in CAV, regional wall motion alterations are less evident. Echocardiographic (ECHO) strain imaging reveals alterations in myocardial contraction not detectable by conventional ECHO. Thus, we assessed its reliability in distinguishing between patients with and without CAV. Methods: All consecutive transplanted patients without visible alterations of LV kinetics underwent speckle tracking derived 2D strain analyses at rest, before coronary angiography. LV radial, circumferential and longitudinal strain and strain-rate (Sr) were measured and also dyssynchrony and end-systolic dyssynergy indexes were calculated from strain curves. 2D strain data were tested for relationship to angiographic findings. Results: Of 187 evaluated patients, 56 had no CAV (group 1), 87 diffuse coronary type-B lesions (group 2) and 44 proximal focal stenoses (group 3). Whereas conventional ECHO showed no predictive value for coronary stenoses, certain strain and Sr parameters and indexes appeared predictive for detection of patients with CAV (Fig 1). Thus, the time to peak longitudinal Sr (TpLSr) and the peak longitudinal Sr/TpLSr index showed up to 93.1% and 94.6% sensitivity and specificity, respectively, for differentiation between group 1 and 2. The ayssynchrony and dyssynergy indexes for longitudinal shortening also allowed differentiation between group 2 and 3 (sensitivity and specificity: up to 86.3%). Conclusions: 2D strain imaging is reliable for CAV prediction and also helpful for differentiation between patients with and without focal coronary stenoses. Our results recommend 2D strain as a non-invasive tool with the potential to facilitate early detection of stenoses and to enable angiographies to be timed, sparing patients frequent routine angiographies.
Abstract 17857: Calpain-2 Protects Against Doxorubicin-Induced Cardiac Toxicity
Authors: Dong Zheng, Rui Ni, Yanpeng Wang, Tianqing Peng
Journal: Circulation (2013)

Background: Doxorubicin, a highly effective chemotherapeutic agent, can cause cumulative dose-dependent cardiotoxicity, which may present as cardiomyopathy. We have recently demonstrated that inhibition of calpain increases apoptosis in cardiomyocytes and aggravates myocardial dysfunction and mortality in mice with calpastatin over-expression. This study suggests that endogenous calpain may provide cardioprotection in doxorubicin-induced toxicity. Objective: The present study was to investigate which isoforms of calpain would protect against doxorubicin-induced cardiotoxicity. Methods and Results: In cultured neonatal cardiomyocytes, over-expression of calpain-2 attenuated apoptosis induced by doxorubicin whereas calpain-1 slightly enhanced apoptosis. The inhibitory effect of calpain-2 on apoptosis correlated with up-regulation of AKT signaling and a reduction in histone H2AX phosphorylation. These results indicate a protective role of calpain-2 in doxorubicin-induced cardiotoxicity. To study the in vivo ...
Abstract 9400: Inhibition of IκB Phosphorylation by a Novel IKK Inhibitor IMD-1041 Attenuates Myocardial Dysfunction After Infarction
Authors: Ryo Matsumoto, Jun-Ichi Suzuki, Masahito Ogawa, Ryo Watanabe, Susumu Muto, Akiko Itai, Yasunobu Hirata, Ryozo Nagai, Mitsuaki Isobe
Journal: Circulation (2011)

Background: Ischemia after myocardial infarction (MI) frequently causes left ventricular (LV) dysfunction. This condition is due to inflammatory reactions and fibrosis of myocardium. LV remodeling after MI is the pathological process which includes expansion of the infarcted area, ventricular dilatation and distortion of the ventricular shape. Recently, several studies have demonstrated that nuclear factor-kappa B (NF-κB) is related to inflammation and LV remodeling and that NF-κB is activated in infarcted hearts. However, the effects of the continuous inhibition of NF-κB for the prevention of LV dysfunction after MI are still controversial. A novel IKK inhibitor IMD-1041, which inhibits phosphorylation of I-κB via inhibition of IKK-β, is under clinical trial for chronic obstructive pulmonary disease. In spite of these progressive studies on pulmonary disease, the effects of IMD-1041 on cardiovascular disease are not yet well examined. The aim of this study was to investigate the effects of IMD-1041 on myocardial remodeling after infarction. Methods and Results: To analyze the effects of IMD-1041 on myocardial dysfunction after MI, we continuously administered IMD-1041 (low dose; 30mg/kg/day, high dose; 100mg/kg/day) or vehicle (0.5% CMC) orally to mice with ligation of the left anterior descending coronary artery (LAD). After 28 days of ligation, MI mice exhibited LV dilatation and contractile dysfunction. However, IMD-1041 treatment significantly improved cardiac function, as indicated by the preservation of fractional shortening (30mg/kg/day of IMD-1041, 25.8±0.8%, n=12; 100mg/kg/day of IMD-1041, 29.3±0.6%, n=12; vehicle-treated, 21.6±1.6%, n=11; P&lt;0.05). Histological analysis also showed that IMD-1041 treatment effectively inhibited LV remodeling through reduction of the ratios of fibrosis per whole area compared with vehicle control group (30mg/kg/day of IMD-1041, 21.5±2.0%, n=12; 100mg/kg/day of IMD-1041, 24.0±1.7%, n=12; vehicle-treated, 33.2±3.6%, n=11; P&lt;0.05). Conclusion: These results suggest that IMD-1041 treatment effectively improves LV remodeling after MI through attenuation of myocardial fibrosis. It may provide an effective approach to prevent myocardial dysfunction.
Abstract 3432: Patients with Upper Extremity Arterial Disease Have Similar Major Adverse Clinical Events as Those with Lower Extremity Arterial Disease
Authors: Yung-Wei Chi, T. Cooper Woods
Journal: Circulation (2007)

Introduction: Upper extremity arterial disease, although it occurs less frequently compared to lower extremity arterial disease, negatively impacts one’s lifestyle. Most studies on peripheral arterial disease have been focused on the lower extremities and the clinical impact of upper extremity arterial disease remains less well known. Hypothesis: Patients with upper extremity arterial disease have similar major adverse cardiovascular events (MACE) as those with lower extremity arterial disease. Methods: Sixty-seven consecutive patients with upper extremity arterial studies and 359 consecutive patients with lower extremity arterial studies performed in 2004 by an accredited vascular laboratory were followed for at least 2 years. MACE including death, stroke, transient ischemic attack (TIA), myocardial infarction (MI) and unstable angina (USA) were tabulated and compared between the 2 groups. Final results were adjusted for diabetes mellitus, hypertension, hyperlipidemia, smoking status, and renal insufficiency. One-tailed t test was used. Results: Eight events (28%) occurred in 29 patients with abnormal upper extremity arterial study compared to 24 events (21%) in 112 patients with abnormal lower extremity arterial study, p=NS. Five events (13%) occurred in 38 patients with normal upper extremity arterial study compared to 8 events (28%) in those with abnormal upper extremity arterial study, p=0.02. Twenty events (8%) occurred in 247 patients with normal lower extremity arterial study compared to 24 events (21%) in those with abnormal lower extremity arterial study, p&lt;0.0001. Conclusion: Patients with upper extremity arterial disease defined by abnormal upper extremity arterial study have similar MACE to those with lower extremity arterial disease (28% versus 21%, p=NS). In addition, those with either upper or lower extremity arterial disease have statistically more MACE than those without disease. Major Adverse Clinical Events
Detection of subclinical systemic disease in primary central nervous system lymphoma (PCNSL) by polymerase chain reaction (PCR) of the rearranged immunoglobulin heavy chain (IgH) genes
Authors: K. Jahnke, M. Hummel, A. Korfel, T. Burmeister, H. Mueller, C. Seide, H. Stein, E. Thiel
Journal: Journal of Clinical Oncology (2006)

1533 Background: An unresolved question is why some PCNSL spread systemically while most others do not. It was postulated that extracerebral relapse of PCNSL may represent a sequel of initial occult systemic disease rather than true extracerebral spread. Methods: To elucidate this question, we examined bone marrow and peripheral blood specimens of 24 patients with newly diagnosed PCNSL using PCR for the presence of clonally rearranged IgH genes. The applied IgH PCR method was recently developed by a European Concerted Action (BioMed-2). To all samples (50 ng DNA), three different FR primer sets (FR1, FR2 and FR3) were applied in conjunction with a JH consensus primer (JH22). Baseline routine staging procedures showed no evidence of systemic lymphoma manifestations in all patients. Results: The same dominant PCR products were found in bone marrow aspirates, blood samples and tumor biopsy specimens from three patients, indicating the presence of the same tumor cell population in the CNS as well as in extracerebral sites. No concordant dominant amplificates were detectable in the remaining 21 patients. To date, nine patients have relapsed intracerebrally and none systemically after a median follow-up of 25 months. Median overall survival was 30.5 months. Of the three patients with monoclonality outside the CNS, two are still in complete remission 24 and 25 months after diagnosis, respectively. The third patient relapsed intracerebrally 12 months after diagnosis, achieved complete remission after whole-brain irradiation and died in complete remission 16 months after diagnosis due to pulmonary embolism. Conclusions: Extracerebral disease not detectable by routine staging may be present in PCNSL patients. This finding may have an impact on the understanding of PCNSL pathogenesis and the extent of staging and treatment. No significant financial relationships to disclose.
Abstract 382: Kidney-Heart Connection: One Kidney Nephrectomy Results in Cardiac Fibrosis and Differential Ventricular Gene Profiles in the Absence of Heart Failure
Authors: Fernando L Martin, Brenda K Huntley, Gerald E Harders, John C Burnett
Journal: Circulation (2007)

Background: Decreased renal function is associated with increased cardiovascular morbidity and mortality by mechanisms that remain unclear. We hypothesized that even mild renal insufficiency produced by unilateral nephrectomy results in changes in ventricular structure and gene expression in the absence of hypertension or volume overload underscoring a kidney-heart connection in the control of myocardial structure. Methods: Cardiorenal function and structure were assessed in Wistar rats [sham (S; n=10) and unilateral nephrectomized (UNX; n=9)] 4 weeks after UNX. GFR was determined by inulin clearance and renal blood flow (RBF) by PAH. Blood was obtained for BNP, PRA, and aldosterone. Hearts and kidneys were harvested for histological analysis. Cardiac function was assessed by echo. Genome-wide microarray analysis was performed on left ventricular myocardium (Affymetrix GeneChip® Rat Genome 230 2.0). Results: Glomerular hypertrophy was observed in UNX (S:1±0.04, Nx:1.6±0.1 u3x106, p&lt;0.001). GFR tended to decrease with a reduction in RBF (S:8±1, Nx:5±1 ml/min, p&lt;0.005). Sodium and water excretions were not different between groups with no activation of PRA, aldosterone or BNP. LVEF and LV end-systolic and end-diastolic diameters were normal. Blood pressure (BP) was not different between groups. Importantly, Picrosirius Red staining in the ventricular myocardium of UNX compared to S revealed greater fibrosis (S:2.4±0.1, Nx:4.2±0.4 %, p&lt;0.001). Further, microarray analysis of ventricular myocardium revealed that 278 genes significantly changed with UNX (1.5 fold, P&lt;0.05) compared to S in genes related to cell growth, bone remodeling and muscle contraction (Z value&gt;2). Conclusion: We conclude that even mild renal insufficiency produced by unilateral nephrectomy initiates myocardial gene responses and fibrosis independent of alterations in the circulating RAAS, BNP, BP, volume overload or systolic dysfunction. These studies support a kidney - heart connection in early renal dysfunction resulting in molecular ventricular remodeling and fibrosis. These studies in experimental mild renal dysfunction produced by removal of one kidney reveal a renal mediated mechanism for myocardial remodeling.
Central But Not Brachial Blood Pressure Predicts Cardiovascular Events in an Unselected Geriatric Population
Authors: Riccardo Pini, M. Chiara Cavallini, Vittorio Palmieri, Niccolò Marchionni, Mauro Di Bari, Richard B. Devereux, Giulio Masotti, Mary J. Roman
Journal: Journal of the American College of Cardiology (2008)
Abstract 4947: Maintenance Treatment With Ticagrelor Yields Greater and More Consistent Inhibition of Platelet Function Compared to Clopidogrel in Patients With Acute Coronary Syndromes: Results From the PLATO PLATELET Substudy
Authors: Robert F Storey, Dominick J Angiolillo, Shankar B Patil, Bhaloo Desai, Steen Husted, Håkan Emanuelsson, Lars Wallentin
Journal: Circulation (2009)

Background: The PLATO study compared the efficacy of ticagrelor (T), an oral reversible P2Y 12 receptor antagonist, and clopidogrel (C) in patients with non ST elevation ACS or primary PCI-treated STEMI patients. In the PLATO PLATELET substudy, we assessed the extent of inhibition of platelet function in PLATO study patients. Methods and Results: 69 patients randomised in the PLATO study to receive maintenance therapy with either C 75mg qd (n=32) or T 90mg bid (n=37) underwent platelet function testing after at least 28 days of treatment. Light transmittance aggregometry (LTA) with ADP (5 and 20 uM), VerifyNow P2Y12 (VN) and VASP assays were performed prior to maintenance dose (‘trough’) and 2– 4h after dosing (‘peak’) in all patients. Mean % maximum LTA response induced by ADP 20 uM at trough was 48±14 and 36±12% (p&lt;0.001) and at peak was 44±15 and 28±10% for C and T respectively (p&lt;0.0001)(Figure ). Similar patterns were seen for ADP 5 uM. VN values at trough were 214±79 and 79±78 PRU for C and T and at peak were 196±95 and 31±32 PRU respectively (both p&lt;0.0001)(Figure ). PRI values at trough were 55±22 and 27±21% for C and T and at peak were 44±21 and 14±13% respectively (both p&lt;0.0001). VN and VASP at peak particularly showed more consistency and less variability in response with T compared to C. Conclusion: Maintenance therapy with ticagrelor 90mg bid in patients with ACS achieves greater and more consistent inhibition of platelet function compared to standard clopidogrel therapy.
Abstract 10062: Immunoglobulin Treatment Suppresses Free Radical-Medicated Myocardial Injury in Experimental Autoimmune Myocarditis
Authors: Chiharu Kishimoto, Taka-aki Okabe, Zuyi Yuan, Keisuke Shioji
Journal: Circulation (2010)

Background and Purpose: Recent evidence suggests that free radicals may play a crucial role in heart failure. We tested the hypothesis that immunoglobulin ameliorated experimental autoimmune myocar...
Bipolar mood disorder and endometriosis: preliminary findings
Authors: D O Lewis, F Comite, C Mallouh, L Zadunaisky, K Hutchinson-Williams, B D Cherksey, C Yeager
Journal: American Journal of Psychiatry (1987)

A consecutive sample of 16 women with laparoscopy-diagnosed endometriosis were evaluated for mood disorders. Twelve women met DSM-III criteria for a mood disorder: seven for bipolar disorder, mixed, three for bipolar disorder, manic, and two for major depression. Two women had equivocal diagnoses and two showed no evidence of mood disorder. Nine subjects had first-degree relatives with histories of severe mood disorders.
Advice on reducing cholesterol should be included
Authors: T Reynolds, A Wierzbicki
Journal: BMJ (1995)

EDITOR,—John McMurray and Andrew Rankin's review of treatment of myocardial infarction and angina and subsequent advice on lifestyle modifications does not mention the advisability of reducing cholesterol concentrations.1 This is interesting given that large studies have shown cholesterol reduction to be effective in inducing the regression …
Abstract 16067: miR-148a is a Novel Repressor of NF-kB Signaling in Aortic Valve Calcification
Authors: Katrina Carrion, Vishal Patel, Jeffery Dyo, Andrew Holland, Thomas Gallegos, Gerard Hardiman, Salah Mohamed, Emma Leire, Sanjay Nigam, Victor Nizet, Vishal Nigam
Journal: Circulation (2013)

The purpose of this study was to identify novel modulators of the inflammatory pathways associated with aortic valve calcification. Bicuspid aortic valves (BAV) are at the highest risk of developin...