tbuckley/cabot-search huggingface dataset:
Abstract 1509: Inducible TBX3 Overexpression As A Tool For Biopacemaker Engineering
Authors: Gerard J Boink, Martijn L Bakker, Arie O Verkerk, Diane Bakker, Jacques M de Bakker, Jurgen Seppen, Vincent M Christoffels, Hanno L Tan
Journal: Circulation (2008)

Introduction: Currently constructed biopacemakers based on single gene transfer strategies function suboptimally, with periods of slow heart rates and instabilities during rest. In the sinoatrial node (SAN), the dominant native pacemaker, multiple genes are required for proper impulse formation and impulse propagation. TBX3 is an important regulator of the SAN gene program during heart development. We examined the effects of inducible TBX3 overexpression in adult hearts and in vitro we explored whether lentiviral TBX3 overexpression may be used in biopacemaker engineering. Methods: In vivo atrial and ventricular expression levels of the connexin isoforms Cx43 and Cx40 (impulse propagation) and SCN5A were studied in mice with tamoxifen inducible overexpression of TBX3 using quantitative PCR analysis. Single neonatal rat cardiac myocytes were transduced with TBX3 expressing lentivirus to analyze the effects of TBX3 on action potentials and membrane currents (impulse formation) using the perforated patch-clamp technique. Results: In vivo, Cx43, Cx40 and SCN5A, which are not or only moderately expressed in the native SAN, were severely down-regulated to 20%, 15%, and 40%, respectively, by TBX3 (n=12; p&lt;0.01). Single neonatal cardiac myocytes overexpressing TBX3 exhibited faster spontaneous beating rates, along with decreased maximum diastolic potential, inward rectifier potassium current (I K1 ), and fast sodium current (I Na ). These properties are typical of SAN pacemaker cells. Conclusions: TBX3 can act as a strong repressor of the working myocardium gene program in the adult heart. Overexpression of TBX3 might be a useful tool in biopacemaker gene and cell therapy.
Prognostic Impact of Staged Versus “One-Time” Multivessel Percutaneous Intervention in Acute Myocardial Infarction
Authors: Ran Kornowski, Roxana Mehran, George Dangas, Eugenia Nikolsky, Abid Assali, Bimmer E. Claessen, Bernard J. Gersh, S. Chiu Wong, Bernhard Witzenbichler, Giulio Guagliumi, Dariusz Dudek, Martin Fahy, Alexandra J. Lansky, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2011)
Abstract 3739: The Influence of Albuminuria on Mortality in Patients with Stable Coronary Artery Disease
Authors: Scott D Solomon, Julie Lin, Caren G Solomon, Kathleen Jablonski, Madeline Murguia Rice, Michael Steffes, Michael Domanski, Judith Hsia, Bernard J Gersh, J. Malcolm O Arnold, Jean Rouleau, Marc A Pfeffer
Journal: Circulation (2007)

Background: Patients with chronic kidney disease are at increased risk for cardiovascular morbidity and mortality. We assessed the association between albuminuria and death or cardiovascular events among patients with stable coronary disease. Methods: We studied patients enrolled in the Prevention of Events with an ACE Inhibitor (PEACE) trial, in which patients with chronic stable coronary disease and preserved systolic function were randomized to trandolapril or placebo and followed for a median of 4.8 years. The urinary albumin to creatinine ratio (ACR) assessed in a core laboratory in 2977 patients at baseline and in 1339 patients at follow-up (mean 34 months) was related to estimated glomerular filtration rate (eGFR) and outcomes. Results: The majority of patients (73%) had a baseline albumin/creatinine ratio within the normal range. Independent of the eGFR and other baseline covariates, a higher albumin/creatinine ratio even within the normal range was associated with increased risks for all-cause mortality (p &lt; 0.001) and cardiovascular death (p = 0.01). The effect of trandolapril therapy on outcomes was not significantly modified by the level of albuminuria. Nevertheless, trandolapril therapy was associated with a significantly lower mean follow-up ACR (12.5 ug/mg vs 14.6 ug/mg, p = 0.0002), after adjusting for baseline ACR, time between collections and other covariates. An increase in ACR over time was associated with increased risk of cardiovascular death (HR per log ACR 1.74, 95% confidence intervals 1.08–2.82). Conclusions: Albuminuria, even in low levels within the normal range, is an independent predictor of cardiovascular and all-cause mortality.
Abstract 2562: Two-Year Clinical Follow-Up of COREA-TAXUS Trial: Long-Term Safety And Efficacy of Celecoxib for 6 Months After Paclitaxel-Eluting Stents Implantation
Authors: Jin-Wook Chung, Han-Mo Yang, Dong-A Kwon, Jung-Won Suh, Kyung-Woo Park, Hyun-Jai Cho, Sang-Hyun Kim, Cheol-Ho Kim, Byung-Hee Oh, Young-Bae Park
Journal: Circulation (2008)

Background: The effect of celecoxib on restenosis after angioplasty with a Taxus stent (COREA-TAXUS) trial is an open-label randomized controlled study, where we reported celecoxib was effective in reducing 6months late loss of Taxus stent. With this cohort, we analyzed long-term clinical outcomes. Method: Two hundred sixty seven patients underwent successful paclitaxel-eluting stents implantation for native coronary lesions. Patients were randomized to receive celecoxib (400 mg before the intervention, and 200 mg twice daily for 6 months after the procedure) or not. Clinical endpoints were cardiac death, non-fatal myocardial infarction, and revascularization of the target lesion. Results: At 6 months, frequency of adverse cardiac events was significantly lower in the celecoxib group (5.3% versus 16.2%, P=0.005), mainly because of reduced need for revascularization of the target lesion (5.3% versus 15.4%, P=0.009). Between 6 and 24 months, frequency of adverse cardiac events was not different between the celecoxib group and the control group (1.6% versus 4.4%, P=NS: 0% versus 0% for cardiac death; 0.8% versus 0.9% for non-fatal myocardial infarction; 0.8% versus 3.5% for revascularization of target lesion, P=all NS). At 2 years, frequency of adverse cardiac events was still significantly lower in the celecoxib group (6.9% versus 19.9%, P=0.002) Conclusion: In the COREA-TAXUS trial, the adjunctive use of celecoxib for 6 months after Taxus stent implantation was safe and clinically effective for 2 years.
Lymphoproliferative syndrome with autoimmunity: A possible genetic basis for dominant expression of the clinical manifestations.
Authors: F Rieux-Laucat, S Blachère, S Danielan, J P De Villartay, M Oleastro, E Solary, B Bader-Meunier, P Arkwright, C Pondaré, F Bernaudin, H Chapel, S Nielsen, M Berrah, A Fischer, F Le Deist
Journal: Blood (1999)
Abstract 4460: Supported High-Risk Percutaneous Coronary Intervention Using The Impella LP2.5 Device. The Europella Registry
Authors: Krischan D Sjauw, Christian Hassager, Paolo L Danna, Thomas Konorza, Annemarie E Engström, Hans-Heinrich Minden, F P Machado, Giovanni Pedrazzini, Daniel R Wagner, Daniel R Wagner, Sebastian Kerber, Rainer Schamberger, Joachim Schofer, Detlef G Mathey, Raimund Erbel, Maurizio Viecca, Thomas Engström, José P Henriques
Journal: Circulation (2008)

Background Patients with complex or high risk coronary lesions, due to extensive and diffuse multivessel, left main or last remaining coronary artery disease are increasingly being treated with percutaneous coronary intervention (PCI). As peri-procedural hemodynamic compromise and complications may occur rapidly, many of these high-risk procedures are being performed with mechanical cardiac assistance, particularly in patients with poor left ventricular (LV) function. The Impella LP2.5, a novel percutaneous implantable LVAD able to provide flow up to 2.5 L/min, may be a superior alternative to the traditionally used IABP. Methods We studied safety and feasibility of LV support with the Impella LP2.5 in 144 high-risk PCI patients. All patients were enrolled in the Europella registry, a prospective multicenter registry comprising 10 high volume tertiary PCI centers in Europe. Results Patients were old (62% &gt;70 years), 53% had previous myocardial infarction, 54% had a LV ejection fraction ≤30% and the prevalence of co-morbid conditions was high. Mean EuroSCORE was 8.2 (SD 3.4) and 43% of the patients were refused for CABG. PCI was considered high risk due to left main, last remaining and multivessel coronary artery disease, and low LV function respectively in 53%, 17%, 81% and 35% of the cases. The mean assist time was 1 hour and 28 minutes (SD 51min). There were no intra-procedural major adverse cardiac and cerebral events. In-hospital and 30-day mortality were 4.7% and 5.5%. Rates of myocardial infarction, stroke, bleeding requiring transfusion/surgery and vascular complications at 30 days were respectively 0%, 0.7%, 1.4% and 4.0% Conclusions The safety and feasibility findings of Impella LP2.5 are encouraging. Our study, supports the potential usefulness of hemodynamic support with Impella LP2.5 to prevent intra-procedural major adverse events and hemodynamic compromise in high-risk PCI.
Abstract 21122: Small Conductance Calcium Activated Potassium Channel and Recurrent Ventricular Fibrillation in Failing Rabbit Ventricles
Authors: Su-Kiat Chua, Mitsunori Maruyama, Tomohiko Ai, Po-Cheng Chang, Tetsuji Shinohara, Mark J. Shen, Zhenhui Chen, Shen Changyu, Lohe Michael Rubart-von der, John C. Lopshire, N Weiss James, Shien-Fong Lin, Peng-Sheng Chen
Journal: Circulation (2010)

Background: Recurrent spontaneous ventricular fibrillation (SVF), or electrical storm, is associated with increased mortality and morbidity. Action potential duration (APD) shortening and late phas...
Abstract 15528: The Valosin-Containing Protein Provides a Novel Mechanism of Preconditioning in vivo
Authors: Paulo Lizano, Eman Rashed, Christophe Depre, Hongyu Qiu
Journal: Circulation (2011)

The valosin-containing protein (VCP) is an Akt-activating protein expressed in cancer cell lines, which activates the transcription factor NF-κB by promoting the ubiquitination and proteasome degra...
Abstract 13411: p90RSK Inhibits C Terminus Of Hsc70-interacting Protein (CHIP) Ubiquitin E3 Ligase Activity And Promotes Cardiac Apoptosis Through ERK5-Ser 496 Phosphorylation And Association
Authors: Nhat Tu Le, Yuichiro Takei, Tetsuro Shishido, Chang-Hoon Woo, Yan Lu, Carolyn McClain, Chen Yan, Cam Patterson, Jay Yang, Jun-ichi Abe
Journal: Circulation (2011)

Nhat Tu Le, 2011 Finalist and Presenting Author
TCR Repertoire Diversity Assessed with Immunosequencing Is Associated with Patient Mortality Following Cord Blood Transplant
Authors: Ryan O Emerson, Sarah Nikiforow, Filippo Milano, Anna M Sherwood, Adrienne Papermaster, Katherine A. Guthrie, Christopher S Carlson, Edus H. Warren, Jerome Ritz, Harlan Robins, Corey S Cutler, Colleen Delaney
Journal: Blood (2014)
Partnership with patients
Authors: A. Blenkinsopp, J. Bashford, D. Dickinson, S. Sims, P. W Golightly
Journal: BMJ (1998)

Editor—In outlining the implications for professionals of the rise of “healthcare consumers” Richards emphasises two elements that are necessary for partnership: information of better quality and greater involvement for patients in decisions.1 In both cases, however, true partnership goes deeper still. Information needs to be designed with the help of patients, and the extent of involvement in decisions needs to be tailored to the individual patient. 

Health professionals and patients have different priorities for information about drug treatment.2 Contrary to the beliefs of some health professionals, patients are keen to know more about possible side effects, although we need a better understanding of the best way to present this information. Information may be too complex or theoretical for patients to follow. The language may be wrongly pitched. When researchers in the United States reviewed literature on systemic lupus erythematosus they found that 89% of materials were too complex for half their patients.3 The advice may not be practical: one leaflet for migraine drugs advised sufferers on “trigger factors to avoid ... such as menstruation.”4 In such cases it is not inaccurate or misleading information but lack of user friendliness that alienates patients. Using patients to test information for patients can help to counter this alienation. One of the three key aspects of information quality that the Centre for Health Information Quality defines is that people who use information participate in designing this information. The challenge for health professionals is to recognise that “informed” and “demanding” patients are not necessarily the same thing. Education for doctors, nurses, and pharmacists needs to embrace the concept of concordance and develop the associated skills. 

One such skill will be identifying how much involvement the patient wants to have in decisions about treatment. Some people wish to make their own decisions, while others prefer to delegate decisions to professionals. In a paper that he presented to the King’s Fund meeting described by Richards, John Ovretveit said that we should avoid thinking that “choice is primarily owned by doctors and is theirs to give away”; we should recognise that “people differ in the amount of choice they want and are capable of using with benefit.” Eliciting patients’ preferences will be a key future task for professionals—in particular, distinguishing between a patient who wishes to receive more information and one who actively wants to make decisions.5
Drug points: Peripheral neuropathy with bezafibrate
Authors: C J Ellis, W E Wallis, M Caruana
Journal: BMJ (1994)

A 26 year old woman pre- sented 17 months after the birth of her second child for some temporary help with the breast feeding of her nephew.The breast feeding of her child had been intermittent after 6-8 months and ceased at 15 months.Lactogenesis had continued with minimal milk expressed.A 28-32 day menstrual cycle had returned by 12 months post partum.A progestogen only pill (levonorgestrel 30 ,ug) had been used since 15 months.A synthetic oxytocin spray (Synto- cinon; Sandoz) was used on day 17 of
A phase I trial of gemcitabine, carboplatin or gemcitabine, paclitaxel and concurrent radiation therapy followed by consolidative gemcitabine and carboplatin for inoperable stage III non-small cell lung cancer: An RTOG study
Authors: H. Choy, S. Swann, C. Walter, G. Whipple, W. Demas, D. Ettinger
Journal: Journal of Clinical Oncology (2005)

7103 Background: Gemcitabine has been recognized as a potent radiation sensitizer, therefore combining Gemcitabine (Gem) with thoracic radiation therapy(TRT) in locally advanced non-small cell lung cancer (LANSCLC) is a logical approach to address the need for better local control. The optimal dose of Gem that can be used with concurrent TRT for LANSCLC has not been well defined. Methods: This phase I trial addresses this question in a two sequence (Seq), “ping-pong” trial to find the maximum tolerated dose for Gem administered with carboplatin(Carbo) and TRT followed by adjuvant chemotherapy (Seq A) and Gem and paclitaxel administered with TRT followed by adjuvant chemotherapy (Seq B). Results: Thirty-five patients have been entered as of 12/04. The escalation rule is that a dose is considered acceptable if, of the first 6 eligible patients on each arm, fewer than 3 experience DLTs. A DLT is defined as acute grade 3/4 non-hem toxicities, grade 4 hem toxicities occurring during concurrent Chemo/TRT; or Grade 3/4 pneumonitis or grade 3/4 delayed onset esophagitis occurring during the consolidation phase. Seq B of this two-seq, “ping-pong” trial closed on 5/22/2003 because of excessive toxicity. On Seq A, escalation has continued from the Arm 1 through 7. MTD has not been reached in seq A as of Arm 5. The study is currently on hold for toxicity assessment of Arm 7. If Arm 7 has fewer than 3 DLTs, study will be re-open at Arm 9 (Gem dose of 750mg/m2/weekly with carbo of 2 AUC). More mature data will be available after patient accrual and toxicity assessments are completed. Conclusions: A detailed analysis of the fields and volumes of TRT and how they relate to the toxicity and efficacy will be presented. These data should provide clear direction for the optimal techniques of incorporating gemcitabine in the setting of concurrent TRT. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, Eli Lilly Aventis, Bristol-Myers Squibb, Eli Lilly
Abstract 13988: Independent Effects of Risk Factors and Treatment on Carotid Intima-Media Thickness Progression in a Community Practice
Authors: Birju Patel, Michael Blaha, Steven Jones
Journal: Circulation (2012)

Background Although carotid intima-media thickness (CIMT) is a well-known predictor of CHD events, the risk factor and treatment determinants of CIMT progression in real world clinical practice are...
Abstract 3234: Both In And Outhospital Worsening Of Renal Function Predict Outcome In Patients With Acute Decompensated Heart Failure
Authors: Kevin Damman, Dirk J van Veldhuisen, Adriaan A Voors, Gerjan Navis, Tiny Jaarsma, Hans L Hillege
Journal: Circulation (2008)

Purpose. Renal impairment and inhospital worsening of renal function (WRF) are common in patients with acute heart failure (AHF) and associated with poor outcome. The effect of WRF after discharge on outcome in these patients is unknown. Methods. The Coordinating Study Evaluating Outcome of Advising and Counseling in Heart Failure (COACH) included 1049 AHF patients. We assessed estimated glomerular filtration rate (eGFR) by the sMDRD formula and serum creatinine at admission, discharge, and 6 and 12 months after discharge. WRF was defined as increase in serum creatinine &gt;0.3mg/dL. The primary outcome was a composite of all-cause mortality and heart failure admissions. Results. Mean age was 71 ± 11 years, 62% were male. Mean eGFR at admission was 56 ± 22 mL/min/1.73m 2 ,with mean LVEF 33 ± 14%. Inhospital WRF occurred in 13% of patients, while 19% and 12% experienced WRF from 0 to 6, and 6 to 12 months after discharge, respectively. WRF was in a landmark analysis associated with poor outcome: hazard ratio (HR) 1.39 (1.07 –1.81), P &lt;0.05 for inhospital WRF, HR 2.70 (1.65 –4.43), P &lt; 0.001 for WRF at 6 months and HR 3.44 (1.81–6.52), P &lt; 0.001 for WRF between 6 –12 months (Figure ). In multivariate analysis, after adjustment for age, gender, LVEF, eGFR and NYHA class, WRF at any point in time was associated with worse outcome: HR 1.33 (1.01 –1.75), P &lt; 0.05 for inhospital WRF, HR 2.50 (1.47 –4.26), P = 0.001 for WRF between 0 – 6 months, and HR 2.81 (1.38 – 5.73), P = 0.004 for WRF between 6 –12 months. Conclusion. Both in and outhospital worsening of renal function are independently related to poor prognosis in patients with AHF, suggesting that renal function in AHF patients should be monitored long after discharge.
A comparison of capecitabine versus infusional 5-FU used concurrently with preoperative radiation for rectal cancer: A population-based study
Authors: H. J. Lim, S. Gill, J. Hay, K. J. Savage
Journal: Journal of Clinical Oncology (2008)

15035 Background: The use of infusional 5-FU has been standard of care with neoadjuvant chemoradiation for rectal carcinoma. Based on phase II data, the pattern of practice has shifted to capecitabine, an oral 5-FU derivative to avoid the logistical complications of delivering infusional 5-FU. We conducted a population based study to compare the local outcomes and toxicity of neoadjuvant chemoradiation in the eras prior to and following the adoption of capecitabine as the preferred strategy. Methods: The B.C. Cancer Agency (BCCA) is a provincial centre which receives all of the referrals for pre-operative radiation for the treatment of rectal cancer. In Oct. 2006, capecitabine was approved for funding and replaced infusional 5FU for neoadjuvant chemoradiation. Through the BCCA pharmacy database and supplemental chart review, we captured clinical information, including: patient demographics, stage, pathology, toxicity and radiation dose from Jan. 2005 to March 2007 to compare these two treatment eras. Clinical staging was based on a combination of CT, MRI or EUS. Responses were determined by pathologic review (pCR). All patients received 45Gy in 25 fractions, some received an additional 5.4 Gy boost. Toxicity was classified as either Grade 3 or 4 or requiring a dose modification. Comparisons were made using Chi Square method. Results: Table 1 outlines patient characteristics and results. A larger proportion of TME surgery was performed in the capecitabine cohort (p= 0.002) otherwise there were no differences between the two groups. There was a non-significant increase in treatment-related toxicity with capecitabine. Conclusions: No significant differences were observed between the use of neoadjuvant infusional 5-FU and capecitabine based on pathologic response. T and N downstaging in addition to toxicity were similar. The pCR response rates are comparable to reported Phase II trials. Further follow-up will be performed to assess relapse-free and overall survival. Capecitabine 52 pts No. of patients (%) Infusional 5-FU 35 pts No. of patients (%) P value Median Age 64 60 M/F 36/16 26/9 0.64 Pre-operative Imaging MRI 17 (32.7) 12 (34.2) 1.00 EUS 19 (36.5) 7 (20) 0.15 Surgery LAR 14 (26.9) 9 (25.7) 0.55 TME 49 (94.2) 24 (68.6) 0.002 Radiation Boost 29 (55.8) 25 (71.4) 0.18 Low rectal (< 5 cm) 27 (51.9) 22 (68.6) 0.38 pCR 11 (21.2) 5 (14.3) 0.57 Microscopic disease 3 (5.8) 5 (14.3) 0.26 T downstage 21 (40.4) 19 (54.3) 0.27 N downstage 22 (42.3) 15 (42.9) 1.00 Toxicity 14 (26.9) 4 (11.4) 0.11 No significant financial relationships to disclose.
Abstract 3318: Ankle Brachial Index (ABI) Is The Single Most Relevant Independent Prognostic Marker For Recurrent Vascular Events. 5 Years Of Follow Up Of The AIRVAG Cohort
Authors: Lorenzo Lopez-Bescos, Benjamin Herreros, Ana I Huelmos, Enrique Puras, Carmen Sanchez, Isabel Gonzalez-Anglada, Carlos Guijarro
Journal: Circulation (2007)
Paradoxical maintenance of E-cadherin following inducible PTEN ablation in Ras or Fos-mediated skin carcinogenesis identifies sentinel mechanisms geared to combat PTEN dysfunction.
Authors: M. Shaw, D. Yao, J.A. Quinn, D.A. Greenhalgh
Journal: British Journal of Dermatology (2006)

E-cadherin, a cell adhesion protein that provides the spatial awareness for regulation of proliferation, differentiation and cell polarity is often lost or mutated in carcinogenesis. E-cad signalling failure to APC/Wnt/Lef1 pathways via β-catenin and ras-MAPK via α-catenin, occurs at the level of cell contact or in downstream effectors, such as the PTEN TSG, which acts as a scaffolding protein to co-ordinate E–cad signalling, and negatively regulates anti-apoptotic AKT expression, MAPK signalling and cell cycle. Given this E-cad/PTEN interaction, E-cad expression was investigated in multistage skin carcinogenesis mediated by epidermal rasHa or fos activation and RU486-inducible PTEN knockout [Δ5PTEN]. Here PTEN loss co-operated with rasHa and rapidly elicited papillomas but malignant conversion was rare, requiring TPA promotion. PTEN synergism with fos gave hyperkeratotic phenotypes expressing atypical differentiation markers and keratoacanthoma-like tumours [KAs] but no carcinomas. Western and immunefluorescence analysis showed that instead of the loss typically observed in carcinomas, all Δ5PTEN/rasHa carcinomas maintained E-cad expression, which became significantly elevated in Δ5PTEN/fos KAs. Thus, in being downstream of E-cad adhesion signalling, PTEN loss may be compensated for by increased or maintained E-cad expression due to a perceived potential threat to barrier maintenance. Such epidermal defence mechanisms possibly evolved to cope with carcinogenic insults yet avoid induction of apoptosis, a default mechanism available to internal epithelia, which would lead to barrier dysfunction. Indeed, the elevation observed in PTEN/fos KAs may echo this sentinel mechanism geared to divert keratinocytes with increased malignant/metastatic potential into differentiation pathways forming benign KA-like tumours and may explain in part why PTEN/rasHa papillomas required TPA promotion to achieve malignancy.