tbuckley/cabot-search huggingface dataset:
Cytotoxic Cell Antigen Expression in Anaplastic Large Cell Lymphomas of T- and Null-Cell Type and Hodgkin's Disease: Evidence for Distinct Cellular Origin
Authors: Laszlo Krenacs, Axel Wellmann, Lynn Sorbara, Andreas W. Himmelmann, Eniko Bagdi, Elaine S. Jaffe, Mark Raffeld
Journal: Blood (1997)
Erlotinib and bevacizumab in chemotherapy-naive performance status 2 patients with advanced non-small cell lung cancer
Authors: T. Al Baghdadi, N. Hanna, S. Bhatia, J. McClean, C. Johnson, M. Yu, D. Taber, W. Harb
Journal: Journal of Clinical Oncology (2009)

e19082 Background: Poor performance status is a negative prognostic variable for survival and a risk for increased toxicities with standard chemotherapy. A phase 2 study combining erlotinib (E) and bevacizumab (B) demonstrated encouraging efficacy in the treatment of recurrent NSCLC with acceptable toxicity. We, therefore, tested this regimen in untreated PS 2 patients with advanced NSCLC. Methods: Single-arm phase 2 trial in treatment-naïve patients with advanced non-squamous NSCLC and either a PS of 2 or age &gt;75. Only patients eligible for bevacizumab per label were allowed onto study. Patients received E 150 mg orally daily and B 15 mg/kg IV on day 1 every 21 days for up to 6 cycles. The primary end-point was the rate of non progressive disease at 4 months (alternative hypothesis P&gt;60%). Other end-points included overall survival, progression free survival (PFS), toxicity evaluations and patient-reported PS (PRPS) measures. Results: 25 patients were enrolled. Patient characteristics: 56% female, median age 77 years (range: 52–90); 88% stage IV; 92% were PS 2; 20% were never or remote smokers (&gt; 30 years) The PRPS was 1, 2, 3 in 32%, 52%, 8% respectively with data on 2 patients missing. The rate of non-progression at 4 months was 40%; overall best response: 5% PR, 40% SD, 50% PD and 5% unevaluable; median PFS 2.6 months, 95% CI (1.3–5.1); MST 5.8 months, 95% CI (3.8- 8.7). 2 patients had G3 rash. G3 diarrhea, G3 hemorrhage, G3 proteinuria, G3 duodenal ulcer and G3 pneumonitis each developed in one patient. Conclusions: E + B is an active regimen with an acceptable toxicity profile; however, this study did not meet its’ primary endpoint. Further study of this combination will not be pursued in the Hoosier Oncology Group for this patient population. [Table: see text]
Abnormal Glucose Regulation Is Associated With Lipid-Rich Coronary Plaque
Authors: Tetsuya Amano, Tatsuaki Matsubara, Tadayuki Uetani, Michio Nanki, Nobuyuki Marui, Masataka Kato, Tomohiro Yoshida, Kosuke Arai, Kiminobu Yokoi, Hirohiko Ando, Soichiro Kumagai, Hideki Ishii, Hideo Izawa, Nigishi Hotta, Toyoaki Murohara
Journal: JACC. Cardiovascular imaging (2008)
Whole-Exome Sequencing In Myelodysplastic Syndromes With 5q- and Normal Karyotype
Authors: Vera Adema, Mar Mallo, Leonor Arenillas, María Díez-Campelo, Elisa Luño, Laura Palomo, Albert Perez-Ladaga, Shawn Yost, Chun-Pei Cheng, Olivier Harismendy, Lurdes Zamora, Blanca Xicoy, Carmen Pedro, Consuelo Cañizo, Carmen Sanzo, Rosario Lopez, Angelina Lemes, Jose Maria Raya, Eduardo Rios, Montserrat Arnan, Raquel de Paz, Joaquin Sanchez, Lourdes Florensa, Rafael Bejar, Francesc Solé
Journal: Blood (2013)
Neuropeptide Y (NPY)
Authors: Kuixing Zhang, Fangwen Rao, Jose Pablo Miramontes-Gonzalez, C. Makena Hightower, Brian Vaught, Yuhong Chen, Tiffany A. Greenwood, Andrew J. Schork, Lei Wang, Manjula Mahata, Mats Stridsberg, Srikrishna Khandrika, Nilima Biswas, Maple M. Fung, Jill Waalen, Rita P. Middelberg, Andrew C. Heath, Grant W. Montgomery, Nicholas G. Martin, John B. Whitfield, Dewleen G. Baker, Nicholas J. Schork, Caroline M. Nievergelt, Daniel T. O'Connor
Journal: Journal of the American College of Cardiology (2012)
Liposomal Formulation of Vincristine Allows for Doubling the Dose Compared to Conventional Vincristine: Results of the First Futility Analysis of the OPTIMAL&gt;60 Study of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL)
Authors: Sascha Duecker, Viola Poeschel, Anne Wolf, Gerhard Held, Niels Murawski, Carsten Zwick, Mathias Haenel, Andreas Viardot, Lorenz H. Truemper, Marita Ziepert, Michael Pfreundschuh
Journal: Blood (2014)
Abstract 16141: The Systemic Use of Bevacizumab Has a Direct Effect on Left Ventricular Function. A Prospective Echocardiography Study
Authors: Christodoulos Stefanadis, Andreas Synetos, Archontoula Michelongona, Eleftherios Tsiamis, Flora Zagouri, Aristotle Bamias, Meletios Athanasios Dimopoulos, Stella Kyvelou, Ioannis Kapelakis, Konstantinos Toutouzas
Journal: Circulation (2011)

Background: Bevacizumab (BV), a humanized monoclonal antibody directed against vascular endothelial growth factor, has shown promising activity in patients (pts) with cancer by inhibiting neovascul...
Abstract 1627: Doppler Fourier Domain Optical Coherence Tomography: A Novel Technique to Analyze Exercise-dependent Changes in Vascular Dynamics of Wild-type and LDL Receptor Knockout Mice in vivo
Authors: Henning Morawietz, Gregor Muller, Julia Walther, Maximliano Cuevas, Claudia Goettsch, Lorenz C Hofbauer, Edmund Koch
Journal: Circulation (2009)
Abstract 1616: The Role For Caveolin And Caveolae In Delayed Protection From Ischemia-reperfusion Injury
Authors: Yasuo M Tsutsumi, Yoshihiro Ishikawa, David M Roth, Hemal H Patel
Journal: Circulation (2008)

Introduction: Caveolae are small, flask-like invaginations of the plasma membrane. Caveolins are structural proteins found in caveolae that have scaffolding properties to allow organization of signaling. We have recently shown that both caveolin-1 and caveolin-3 knockout (Cav-1 KO and Cav-3 KO, respectively) mice are unable to be protected from myocardial ischemia-reperfusion injury by acute treatment with volatile anesthetics. Therefore, we tested the hypothesis that delayed cardiac protection induced by volatile anesthetics is caveolin-dependent. Methods: Biochemical assays were performed in excised hearts. Electron microscopy was used to assess caveolae formation. An in vivo mouse model of ischemia-reperfusion injury with delayed anesthetic preconditioning (delayed APC) was tested in wild-type (WT), Cav-1 KO, and Cav-3 KO mice. Mice were exposed to 30 min isoflurane or oxygen and allowed to recover for 24 h. After 24 h recovery, mice underwent 30 min left anterior descending coronary artery occlusion, followed by 2 h of reperfusion at which time infarct size was determined. Results: To elucidate a role for caveolins in delayed APC, wild-type mice were exposed to delayed APC and hearts were fractionated on a discontinuous sucrose gradient to isolate buoyant caveolar membranes. Delayed APC increased the amount of Cav-3 protein but not Cav-1 protein in buoyant fractions. Glucose transporter-4 (GLUT-4), known to interact with Cav-3 and affect cardiac protection, was also increased in buoyant fractions after APC. Microscopically distinct caveolae were observed in WT and Cav-1 KO mice but not Cav-3 KO mice. We assessed the impact of caveolae formation in induction of delayed APC. Infarct size as a percent of the area at risk was reduced by isoflurane in WT (24.0 ± 2.5% vs. 45.1 ± 2.9%, p &lt; 0.05) and Cav-1 KO mice (27.2 ± 4.4%). Cav-3 KO mice did not show delayed APC (41.5 ± 2.2%). Conclusions: These results demonstrate that isoflurane-induced delayed preconditioning involves translocation of Cav-3 and GLUT-4 to caveolae and the presence of microscopically distinct caveolae (dependent on Cav-3 expression) are a requisite for induction of delayed protection in the myocardium. This research has received full or partial funding support from the American Heart Association, AHA Western States Affiliate (California, Nevada &amp; Utah).
Abstract 596: Therapeutic Hypothermia After Cardiac Arrest: A Cost-Effectiveness Analysis
Authors: Timothy J Mader, Jennifer J Bowdoin, Carrie J Nobles
Journal: Circulation (2008)

Background: Mild induced therapeutic hypothermia (TH) is currently recommended for survivors of out-of-hospital cardiac arrest (OHCA) who meet specified criteria. If TH were fully implemented in the US, 2298 additional OHCA victims every year could be expected to survive. Despite a 2006 meta-analysis clearly demonstrating a decrease in mortality and an improvement in neurological outcome (with no treatment-limiting side effects) for TH, clinicians have been reluctant to adopt the therapy, often citing cost as a reason. The aim of this study was to determine the cost-effectiveness (CE) of TH after OHCA relative to supportive care. Methods: Monte Carlo simulation was used to approximate the cost per in-hospital death prevented, the cost per poor neurological outcome averted, and annual hospital costs. Estimates of effectiveness and resource use were extracted from secondary data sources. Included variables were: in-hospital mortality, neurological status, ICU and hospital ward length-of-stay (LOS), ICU and hospital ward cost/day, equipment costs, physician time, and medications. For our base case, we calculated the CE of treating 60 patients/year using a moderate cost method. We did sensitivity analyses through systematic bidirectional adjustments of selected variables’ costs, by reducing the treated patients/year to 12, and by excluding the cost of medications and physician time. All analyses were done from a US hospital perspective and reported in 2008 US$. Results: LOS dominated the difference in cost. The median cost per death prevented was $280,092 [IQR $202,279-$386,215] and per poor neurological outcome averted it was $147,314 [IQR $118,009-$182,251]. The median annual cost to treat 60 patients/year using a moderate cost method was $1,588,730 [IQR $1,322,343-$1,865,462]. Reducing the number of patients treated per year to 12 lowered the annual cost to $319,759 [IQR $268,122-$373,670]. The results of all other sensitivity analyses were similar to the base case. Assuming a mean duration of survival following hospital discharge of 6.13 years, TH had a cost/life-year saved of $45,692, which compares favorably to other life-saving health and social interventions. Conclusion: TH after OHCA is a relatively cost-effective treatment modality.
Scandinavian Clinical Study of Finasteride in the Treatment of Benign Prostatic Hyperplasia
Authors: H.O. Beisland, B. Binkowitz, E. Brekkan, P. Ekman, M. Kontturi, T. Lehtonen, P. Lundmo, F. Pappas, E. Round, D. Shapiro, E. Stoner, R. Swartz, E. Varenhorst
Journal: European Urology (1992)
New Technologies in Cardiovascular Research: Gene Therapy
Authors: Marja Hedman, Mikko P. Turunen, Seppo Ylä-Herttuala
Journal: Cardiovascular Research (2006)

Gene therapy has become an alternative possibility for the treatment of cardiovascular diseases. The studies in cardiovascular gene therapy are mainly focused on inducing therapeutic angiogenesis and cytoprotection and on the inhibition of vascular graft restenosis. Also, disorders of lipid metabolism and the whole process of atherosclerosis are under intensive exploration. On the other hand, as the pathogenesis of different multifactorial vascular diseases has been explored, new targets have emerged for cardiovascular gene therapy. Currently, the main obstacles of gene therapy are the low efficacy of different gene delivery vectors and the difficulty of targeting genes into specific cells. Studies focused on developing not only the appropriate and optimal gene delivery techniques but also suitable models for human diseases are essential for the further development of cardiovascular gene therapy.
Abstract 12912: The Plasma Membrane Calcium Pump (PMCA4) Modulates Cardiac Contractility by Tethering Neuronal Nitric Oxide Synthase to the Plasma Membrane Compartment
Authors: Tamer M Mohamed, Delvac Oceandy, Nasser Alatwi, Min Zi, Sukhpal Prehar, Florence Baudoin, Elizabeth J Cartwright, Ludwig Neyses
Journal: Circulation (2010)

Calcium is involved in the regulation of two essential processes in the myocardium: myofilament contraction and signal transduction. We have previously shown in animals overexpressing the plasma me...
Abstract 2357: Effect of Prolonged Thienopyridine Use on Long-term Clinical Outcomes After Drug-eluting Stents: Landmark Analysis from the TAXUS Trials
Authors: Gregg W Stone, Stephen G Ellis, David K Kong, Joerg Koglin, Mark I Friedman, Donald S Baim
Journal: Circulation (2007)

Background A recent non-blinded, observational landmark study from uncontrolled registry data by Eisenstein et al. suggested that thienopyridine (T) use beyond 1 year may reduce death and MI in patients who have received drug-eluting stents (DES). We performed a similar examination of slow-release paclitaxel-eluting stents (PES) in the prospective, randomized, double-blind TAXUS DES trials. Methods Using data from the TAXUS II-SR, IV and V trials, a landmark analysis was performed on the 2,523 patients who were free of death, MI and stent thrombosis (ST) through 1 year. Patients were divided according to stent type (PES vs bare metal stent [BMS]) and thienopyridine usage at a 1-year landmark point: PES T+ (N=578), PES T− (N=683), BMS T+ (N=574), and BMS T− (N=688). Subsequent events (ST, death, MI) were tabulated for the next 3 years in TAXUS II-SR and IV, and for 1 year in TAXUS V. Results Thienopyridine and aspirin usage were well matched between BMS and PES patients at all time-points. T+ patients at 12 months had no ST events through 4 years, while T− patients had 6 ST events (0.57%; p=0.045, log-rank). This difference was not significant for BMS T+/T− (0.0% versus 0.22%, p=0.49), and borderline significant for PES T+/T− (0.0% versus 0.92%, p=0.056). There was no corresponding difference in death at either 2 or 4 years, but there was a borderline reduction in MI at 2 years for PES T+/T− (0.35% versus 1.49%, p=0.08; interaction term p=0.09 between stent type and thienopyridine use), which disappeared at 4 years (2.79% versus 3.42%, p=0.565; interaction term p=0.35). Conclusions Thienopyridine use at 1 year was associated with fewer subsequent late ST events overall, which was more pronounced for PES than BMS. While there was a borderline reduction in MI at 2 years, no sustained impact on death or MI at 4 years was demonstrated. These data will be updated with one additional year of follow-up in all 2,523 patients at the time of presentation.
Abstract 332: Circulating CCN1 Promotes Angiogenesis via Interaction with Blood CD34 <sup>+</sup> Cells
Authors: Karsten Grote, Gustavo Salguero, Marc Dangers, Matthias Ballmaier, Bernhard Schieffer
Journal: Circulation (2007)

Introduction: CCN1 is so far known as a protein of the extracellular matrix mediating proliferation, adhesion, migration and angiogenesis in an integrin-dependent manner. We recently reported that CCN1 is up-regulated under pathophysiological conditions in the cardiovascular system. Since blood CD34 + progenitor cells have been shown to promote tissue regeneration, we investigated if CCN1 induces angiogenesis by stimulating blood CD34 + cells. Methods and Results: Circulating CCN1 was detected for the first time in human serum samples (Western blot). Rekombinant CCN1 (100 ng/mL) and supernatants from CCN1-stimulated human CD34 + progenitor cells promoted tube-formation (Matrigel-Assay; P &lt; 0.05; n = 4) and proliferation of endothelial cells (BrdU-incorporation; P &lt; 0.05; n = 4). Moreover, CCN1 significantly induced angiogenesis in the context of blood CD34 + cells in vivo determined in Matrigel implanted into C57/BL6 mice as measured by the hemoglobin content (Drabkin’s reagent) and by CD31 staining (immunohistochemistry). In addition, CCN1 induced migration (Transwell cell culture inserts; 7.3 ± 1.3; P &lt; 0.05; n = 4), transendothelial invasion (Transwell cell culture inserts; 2.3 ± 0.7; P &lt; 0.05; n = 3) of CD34 + progenitor cells and release of various growth factors, chemokines (protein array; e.g. G-CSF, GM-CSF, CCL2, TGF-β1) and matrix metalloproteinase-9 (zymography; 2.5 ± 0.5-fold; P &lt; 0.05; n = 6) from these cells. CD34 + progenitor cells expressed the CCN1-specific integrins α M β 2 and α V β 3 (flow cytometry) and binding of CCN1 to CD34 + progenitor cells was diminished by integrin antagonizing RGD peptides. Furthermore, CCN1 stimulated integrin-dependent signaling in CD34 + progenitor cells as shown by enhanced phosphorylation of focal adhesion kinase (immunofluorescence) and promoted their adhesion to endothelial cells which could be inhibited with RGD peptides (P &lt; 0.01; n = 4). Conclusion: Circulating CCN1 binds integrin-specific to CD34 + blood cells and thereby induces migration, adhesion and the release of chemokines and MMPs. Moreover, CCN1-dependent stimulation of blood CD34 + cells promotes endothelial cell proliferation and angiogenesis known to be important for tissue regeneration.
Abstract 14994: Reversibility of Contractile Dysfunction in Patients with Hypertensive Heart Disease
Authors: Susan Cheng, Kaitlyn O'Brien, Juan Pablo Albisu, Beejal Shah, Amil Shah, Akshay Desai, Joseph Izzo, Suzanne Oparil, Bertram Pitt, Scott D Solomon
Journal: Circulation (2011)

Background: Hypertension is frequently associated with the presence of diastolic dysfunction, which may be ameliorated by anti-hypertensive treatment. Prior studies suggest that hypertension is als...
Abstract 1832: A Noninvasive Strategy of Carotid Intimal-Media Thickness Assessment and Transthoracic Echocardiography Identifies Unexplained Stroke Patients with a Low Yield of Transesophageal Echocardiography.
Authors: R Parker Ward, Sascha N Goonewardena, Georgeanne Lammertin, Roberto M Lang
Journal: Circulation (2006)
Abstract 8798: Ethnic Differences in the Phenotypic Expression of Hypertrophic Cardiomyopathy
Authors: Nabeel Sheikh, Michael Papadakis, Navin Chandra, Saqib Ghani, Rachael Bastiaenen, Abbas Zaidi, Martina Muggenthaler, Hari Raju, Elijah Behr, Sanjay Sharma
Journal: Circulation (2011)

Purpose: Hypertrophic Cardiomyopathy (HCM) is a heterogeneous condition with variable phenotypic expression. Current studies are based on predominantly Caucasian cohorts (white patients; WP), and the phenotypic manifestations of HCM in individuals of African/Afro-Caribbean origin (black patients; BP) are not fully realized. Data in athletes and hypertensive patients indicate that black ethnicity is associated with a greater prevalence of repolarisation abnormalities on the ECG as well as a greater magnitude of left ventricular hypertrophy (LVH), highlighting the importance of defining the HCM phenotype in this ethnic group. Methods: Between 2001 and 2010, 155 consecutive patients with HCM (52 BP, 103 WP) were assessed in 3 specialist cardiomyopathy clinics. All underwent comprehensive evaluation including 12 lead ECG and echocardiography. Results: Black patients exhibited significantly different echocardiographic patterns of LVH, with more concentric (44.2% vs. 30.1%) and apical (28.8% vs. 11.7%) hypertrophy compared to WP, who exhibited more asymmetric septal hypertrophy (57.3% vs. 25.0%) (p=0.004). Black patients exhibited a similar magnitude of LVH compared to WP (maximum left ventricular wall thickness 17.3±4.9 mm vs. 18.8±4.1 mm, p=0.069). Relating to ECG repolarisation abnormalities, BP exhibited significantly more T wave inversions in the lateral leads (76.9% vs. 60.2%, p=0.038) and deep (≥ 0.2 mV) T wave inversions (69.2% vs. 51.5%, p=0.035). Black patients also displayed more ST segment depression (50.0% vs. 35.0%, p=0.071), although this was not statistically significant. In contrast, WP had significantly more pathological Q waves (23.3% vs. 9.6%, p=0.039). Conclusions: Ethnicity appears to exert a significant effect on the ECG and echocardiographic patterns in patients with HCM. A significant proportion of black patients exhibit concentric LVH, highlighting the diagnostic challenges in distinguishing HCM from hypertensive heart disease and physiological adaptation to exercise in black individuals. The greater prevalence of deep T wave inversions and T wave inversions in the lateral leads underscores the importance of further evaluation of black individuals with such ECG repolarisation abnormalities.
Abstract 2096: Impact of PI3/Akt Pathway on Production of Vascular Endothelial Growth Factor and Associated Myocardial Salvage by Mesenchymal Stem Cell wtih Transient Overexpression of Heme Oxygenase-1
Authors: Toshinari Tsubokawa, Chiaki Nakanishi, Shotoku Tagawa, Shu Takabatake, Kensuke Fujioka, Kunimasa Yagi, Hidekazu Ino, Hatsue Ishibashi-Ueda, Masakazu Yamagishi
Journal: Circulation (2009)

Background: Mesenchymal stem cell (MSC) with transient overexpression of Heme Oxygenase-1 (HO-1) has a potential for salvaging ischemic myocardial injury through its anti-oxidative and -apoptotic e...
Abstract 11057: Preoperative Symptomatic Status and Outcome After Valve Replacement in Severe Aortic Stenosis is Correlated With Capillary Density, Degree of Fibrosis and Cardiomyocyte Hypertrophy
Authors: Melissa Swinnen, Hadewich Hermans, Hilde Gillijns, Steven Dymarkowski, Paul Herijgers, Marie-Christine Herregods, Stefan Janssens
Journal: Circulation (2012)
Abstract 15998: Leptin Modulates Cardiac Glucose Metabolism and Attenuates Injury in Acute Myocardial Infarction
Authors: Kenneth McGaffin, William Witham, Keith Yester, Christopher O'Donnell
Journal: Circulation (2011)

Introduction In chronic myocardial infarction (MI), leptin improves survival, and limits structural and functional injury. It is unknown, however, what effect leptin has on cardiac metabolism and o...
Costs and effectiveness of community postnatal support workers
Authors: J. Barlow
Journal: BMJ (2001)

Editor—Hassiotis et al highlight many difficulties in providing services for people with mild learning disability and mental illness.1 Many such people fall between the two proverbial stools of general adult psychiatry and learning disabilities psychiatry. This is particularly so for people with mild learning disability and schizophrenia.

Individuals with mild learning disability are three times more likely than the general population to develop schizophrenia.2 Inpatient psychiatric care is required in many cases. Individuals unknown to a psychiatric service at the point of a first psychotic episode are, in the climate of closure of hospitals for people with learning disability, increasingly likely to be admitted to a general adult psychiatric ward. The effective management of a first episode of schizophrenia has attracted recent attention,3 but in the context of comorbid mild learning disability there are special considerations.

People with comorbidity may present complex management problems, many of which are not commonly seen in people with schizophrenia alone. Recent work has indicated that patients with comorbidity have fewer psychiatric admissions, for longer periods of time, than do patients with schizophrenia alone.4 They are also more likely to have a history of epilepsy, negative symptoms of schizophrenia, and impairment of episodic memory.4 A diagnosis of epilepsy may lead to difficulties with the treatment of schizophrenia, as most antipsychotic drugs (both typical and atypical) are epileptogenic. Negative symptoms are notoriously difficult to treat, and memory difficulties may contribute to poor adherence to treatment.

At the point of discharge from hospital many of these patients require a high level of community support. This is not generally as a consequence of a record of contact with the police, a history of self harm, a history of misusing drugs or alcohol, or having additional psychiatric diagnoses.4 A proportion of patients with comorbidity originate from fragmented families with histories of learning disability or schizophrenia, or both, in family members and may have poor support networks.4

A recent case-controlled study of volumetric cerebral magnetic resonance imaging reported that, in terms of brain structure, patients with comorbidity more closely resemble those with schizophrenia than those with mild learning disability.5 In some cases, premorbid cognitive impairment may be associated with a severe and highly familial subtype of schizophrenia.4,5

Many contemporary studies of schizophrenia exclude people with premorbid mild learning disability; this may restrict our further understanding of the generality of this multifaceted condition.4