tbuckley/cabot-search huggingface dataset:
Abstract 5341: Spatial Heterogeneity Of The Mitochondrial Membrane Potential Underlying Arrhythmias In Pressure Overload Hypertrophy
Authors: Hongwei Jin, Elie R Chemaly, Alex Lyon, Joanne Stocks, Fadi G Akar
Journal: Circulation (2008)

Increased production and/or impaired scavenging of reactive oxygen species (ROS) are a hallmark of mitochondrial dysfunction in structural heart disease. Previously, we demonstrated a mechanism by which depolarization of the mitochondrial membrane potential (mitoVm) caused by ROS release through the mitochondrial benzodiazepine receptor (mBZR) promotes conduction failure. Since pressure overload hypertrophy (PoH) is a major risk factor for sudden death, we hypothesized that instability of mitoVm in PoH predisposes to arrhythmias. Methods: PoH was produced in rats by ascending aortic banding for 4 weeks. LV dysfunction characteristic of PoH was confirmed in vivo using M mode 2D echocardiography. Ultrahigh resolution optical imaging was performed in ex vivo perfused hearts from PoH (n=6) and normal (n=3) rats. Normalized mitoVm was measured using a novel quantitative technique of TMRM imaging with subcellular resolution during a protocol of ischemia (for 7min) and reperfusion. Mean and SD mitoVm across 6400 sites were compared as was the expression of the mBZR gene (PKBS) using western blot analysis. Results: Aortic banding for 4 weeks resulted in a significant increase in LV anteroseptal and posterior wall dimensions consistent with structural remodeling in PoH. Ischemia reperfusion related ventricular fibrillation (VF) was observed in 5/6 PoH and 1/3 normal hearts. Average mitoVm was surprisingly greater in PoH compared to normal hearts during both ischemia (17%, p=0.012) and reperfusion (24%, p=0.004). However, spatial heterogeneity of mitoVm indexed by SD was markedly greater in PoH during ischemia (0.42 vs 0.11, p=0.00007) but not reperfusion (p=0.15). Analysis of mitoVm in susceptible (VF+) versus resistant (VF−) rats revealed a 4X increase in mitoVm heterogeneity in ischemia (p=0.0004) but not reperfusion (p=0.12) in the VF+ group. There were no differences in overall protein content of PKBS between groups indicating that altered mitoVm dynamics are independent of PKBS expression. Conclusions: These data demonstrate that increased spatial heterogeneity of mitoVm during ischemia in PoH promotes VF. Strategies aimed at preventing the desynchronization of mitoVm may form a novel therapeutic approach for combating malignant arrhythmias. This research has received full or partial funding support from the American Heart Association, AHA National Center.
The Developmental Gerstmann Syndrome
Authors: 久子 斎藤
Journal: JAMA (1963)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 17765: A Specific Antidote for Dabigatran: Immediate, Complete and Sustained Reversal of Dabigatran Induced Anticoagulation in Healthy Male Volunteers
Authors: Stephan Glund, Joachim Stangier, Michael Schmohl, Marina De Smet, Dietmar Gansser, Benjamin Lang, Viktoria Moschetti, Steven Ramael, Paul A Reilly
Journal: Circulation (2013)

INTRODUCTION: The new oral anticoagulants are effective alternatives for warfarin but specific antidotes are not yet available for these agents to manage life-threatening bleeding or when emergency surgery is necessary. A specific antibody fragment (Fab) is being developed which binds dabigatran with high affinity and thereby prevents dabigatran inhibition of thrombin. For the first time in human volunteers, we determined whether equimolar doses of Fab would reverse the anticoagulant effects of dabigatran. METHODS: Safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of the Fab were investigated in a randomized, double-blind, placebo controlled study in 145 healthy male volunteers. In part I of the study, subjects received single rising i.v. doses of up to 8 g Fab. In part II, Fab doses of 1 g, 2 g and 4 g were administered as 5 min i.v. infusion in the presence of dabigatran (220 mg bid for 4 days). Concentrations of unbound dabigatran were determined as a measure of pharmacologically ac...
Abstract 9546: Effects of Endogenous Hydrogen Sulfide on Differentiation of Cardiac Stem Cells
Authors: Qianhong Li, Li Luo, Ning Chen, Qinghui Ou, Erin M O'Brien, Fangping Yuan, Gregory N Hunt, Timothy O'Toole, Yiru Guo, Roberto Bolli
Journal: Circulation (2011)

Although hydrogen sulfide (H 2 S) has recently emerged as a novel gaseous transmitter with important cardioprotective properties, nothing is known regarding the role of endogenous H 2 S in modulating cardiac stem cells (CSCs). To clarify this issue, murine lin (-) c-kit (+) CSCs were pretreated with NaHS (an H 2 S donor) at a physiological concentration of 100 uM or β-cyano-L-alanine (BCA, 2 mM) and DL-propargylglycine (PAG, 2 mM; two inhibitors of H 2 S biosynthesis), for 24 h in culture media (CM) for flow cytometric analysis, or continually exposed to the same for 72 h in differentiation media (DM) for determining cardiac protein expression. After 72 h of differentiation, the levels of three major markers, von Willebrand factor (VWF) for endothelial cell (EC), α-smooth muscle actin (α-SMA) for smooth muscle cell (SMC), and α-sarcomeric actin (α-Src) for myocytes, did not change in NaHS treated-differentiated CSCs but were significantly increased in BCA or PAG treated-differentiated CSCs as compared with the differentiated control CSCs (n=4, P &lt;0.05, Fig. A). Furthermore, at 24 h of treatment in the culture media, flow cytometric analysis revealed that NaHS treatment did not change the transcription factors expressed early in the cardiac lineages (Ets-1 for EC; GATA-6 for SMC; GATA-4, MEF-2C and Nkx-2.5 for myocytes), whereas BCA or PAG resulted in markedly elevated expression of Ets-1, MEF-2C, and Nkx-2.5 in CSCs (n=5, P &lt;0.05, Fig. B). These data demonstrate, for the first time, that endogenous H 2 S is involved in the lineage specification of adult cardiac stem cells and that it negatively modulates cardiac transcription factors Ets-1, MEF-2C, and Nkx-2.5, thereby providing insights into myogenesis.
Abstract 15765: Quantitative 3D Echocardiography in Children With Congenital Complete Heart Block: The Effect of Pacing and Lead Position on Ventricular Function and Synchrony
Authors: David A Roberson, Vivian Cui, Rukmini Komarlu, Supaluck Kanjanauthai, Ira Shetty, Bettina F Cuneo, Anne Freter, Frank Zimmerman
Journal: Circulation (2011)

Background: Pacemakers in general and some lead positions in particular may adversely affect ventricular function (fxn) and synchrony (sync) in congenital complete heart block (CCHB). 3D echocardio...
Abstract 15751: The Epigenetic of Becoming a Cardiomyocyte: Elucidating the Link Between HDAC1 and Its Role In Regulating BMP2 Signaling During Cardiovascular Specific Differentiation of Embryonic and Induced Pluripotent Stem Cells
Authors: Eneda Hoxha, Erin Lambers, Veronica Ramirez, Prasanna Krishnamurthy, Suresh Verma, Melissa Thal, Raj Kishore
Journal: Circulation (2011)

Cardiomyocytes derived from embryonic and induced pluripotent stem cells (ES/iPS) provide an excellent source for cell replacement therapies following myocardial ischemia. However, some of the obstacles in the realization of the full potential of iPS/ES cells arise from incomplete and poorly understood molecular mechanisms and epigenetic modifications that govern their cardiovascular specific differentiation. We identified Histone Deacetylase 1 (HDAC1) as a crucial regulator in early differentiation of mES and iPS cells. We propose a novel pathway in which HDAC1 regulates cardiovascular differentiation by regulating BMP2 signaling in differentiating pluripotent cells. Stable HDAC1 knock down mES and iPS clones were created using shRNA vectors. Differentiation through embryoid bodies (EB) was induced in wild type mES cells and iPS cells and in their HDAC1-null counterparts. The ability of these cells to differentiate into cardiovascular lineages was monitored. Compared to wild type cells, HDAC1-null EBs sh...
Abstract 2148: Abnormal T Wave Alternans Could Provide Additional Risk Stratification in Patients with Prolonged QRS Duration
Authors: Takanao Mine, Tetsuzou Kanemori, Hiroaki Nakamura, Tohru Masuyama, Mitsumasa Ohyanagi
Journal: Circulation (2008)

QT dispersion, signal averaged electrocardiogram (SAECG) and T wave alternans (TWA) have been found to be increased susceptibility to life-threatening arrhythmias or cardiac death (LTA/CD). Patients with heart diseases often present prolonged QRS duration (p-QRSd), however the risk stratification in patients with p-QRSd still remains. We investigated whether QT dispersion, SAECG and TWA would provide additional risk stratification in patients with p-QRSd. We studied 52 patients (47 males, mean age 66±9 yrs) with QRS duration ≥ 120ms (34 RBBB type and 18 LBBB type) who had heart diseases (45 coronary artery disease and 7 dilated cardiomyopaty). QT dispersion was measured from standard 12-lead ECG. The filtered QRS duration (f-QRS) and root mean square voltage of the terminal 40ms of the QRS complex (RMS40) were obtained by SAECG. TWA was measured with the CH 2000. TWA was considered positive when the alternans with alternans voltage ≥ 1.9μV and alternance ratio ≥ 3 was sustained ≥ 1 minute in vector magnitude, X, Y, Z, V4 or two precordal leads at heart rate ≤ 110bpm. TWA was classified negative when the alternans wasn’t presented at heart rate ≤ 110bpm and considered indeterminate if the record didn’t meet either positively or negatively. Abnormal TWA was defined as positive or indeterminate. An abnormal TWA test was present in 56% (23 patients had negative TWA, 11 had indeterminate and 18 had positive). During the follow-up periods (69±41 months), 15 patients had life-threatening arrhythmias (n=12) and/or cardiac death (n=7). Univariate analysis revealed left ventricular ejection fraction (LVEF), RMS40 and abnormal TWA (n=29) as significant variables, however there was no significant difference in LTA/CD rate between BBB types, and no associations between QT dispersion and LTA/CD. On logistic regression analysis, only LVEF (p=0.02) and abnormal TWA (p=0.02, odds ratio 9.803 [95%CI 1.430 to 67.207]) were independently associated with LTA/CD. Abnormal T wave alternans could provide additional risk stratification in patients with prolonged QRS duration.
Pediatric Nonpost-Operative Junctional Ectopic Tachycardia
Authors: Kathryn K. Collins, George F. Van Hare, Naomi J. Kertesz, Ian H. Law, Yaniv Bar-Cohen, Anne M. Dubin, Susan P. Etheridge, Charles I. Berul, Jennifer N. Avari, Volkan Tuzcu, Narayanswami Sreeram, Michael S. Schaffer, Anne Fournier, Shubhayan Sanatani, Christopher S. Snyder, Richard T. Smith, Luis Arabia, Robert Hamilton, Terrence Chun, Leonardo Liberman, Bahram Kakavand, Thomas Paul, Ronn E. Tanel
Journal: Journal of the American College of Cardiology (2009)
Abstract 17114: ARIA (Apoptosis Regulator Through Modulating Iap Expression) Regulates Insulin Sensitivity and Predisposition to Obesity Through a Modification of Endothelial Cell Functions
Authors: Yoshiki Akakabe, Koji Ikeda, Masahiro Koide, Youhei Kitamura, Kiyonari Matsuo, Hiroaki Matsubara
Journal: Circulation (2012)

Energy metabolism and glucose homeostasis are intricately regulated, failure of which causes type 2 diabetes and predisposition to obesity. Recently, emerging roles of endothelial cells (ECs) in th...
Abstract 17553: Hypocaloric, but Not Isocaloric, Low Fat Diets Improve Microvascular Nitric Oxide Dependent Vasodilation in Obese Subjects
Authors: Mary Szczurek, Jing-Tan Bian, Christine Ranieri, Ivana Grizelj, Ana Cavka, Austin Robinson, Gordon Marsh, Shane A Phillips
Journal: Circulation (2013)

Introduction:  Obesity is associated with microvascular dysfunction and reduced nitric oxide (NO). While low fat diets improve cardiovascular risk, the contributions of macronutrients, independent of weight loss (WL) on microvascular function is not known. We tested the hypothesis that NO-dependent, vasodilator function in microvessels is improved by low fat diets designed for weight loss (LFWL) compared to low fat weight maintenance (LFWM).   Methods:  Obese adults (BMI= 34 + 4 kg/m2) were randomly assigned to either an energy-restricted LFWL diet (n=11, 500 calorie/day deficit) or an isocaloric LFWM diet designed to maintain weight (n=10). All meals were prepared and delivered for 6 weeks and were modeled after the AHA LF diet (50% CHO; 30% protein; 20% fat). Microvessels (internal diameter, 133±38 μm) were obtained from gluteal subcutaneous fat pad biopsies at weeks 1 (pre) and 6 (post) for vascular reactivity measurements to acetylcholine (ACh; 10-9-10-4 M), and flow (pressure gradients: Δ10-Δ100 cmH2O), with and without L-NAME (10-4 M, NOS inhibitor) or Indomethacin (INDO, 10-5 M, cyclooxygenase inhibitor). Vascular NO was measured by fluorescence microscopy.   Results:  LFWL diet reduced BMI (29.3 + 2.0, p   Conclusion:  We found that 1) low fat diets designed for WL improve microvascular reactivity compared to similar diets not designed for WL and 2) increased vascular NO contributes to the improved microvascular dilation to flow and ACh after 6 weeks of WL on low fat diet. These data suggest that weight reduction (and not the associated changes in macronutrient content) on low fat diet is critical for improved microvascular function.
Influence of hepatic dysfunction on safety, tolerability, and pharmacokinetics (PK) of PTK787/ZK 222584 in patients (Pts) with unresectable hepatocellular carcinoma (HCC)
Authors: I. Koch, A. Baron, S. Roberts, U. Junker, M. Palacay-Ramona, E. Masson, A. Kay, B. Wiedenmann, D. Laurent, J. Cebon
Journal: Journal of Clinical Oncology (2005)

4134 Background: The expression of vascular endothelial growth factors (VEGFs) and VEGF receptors are associated with progression of hepatocellular carcinoma (HCC). PTK787/ZK 222584 (PTK/ZK) is a novel, oral, anti-angiogenesis compound that blocks tyrosine kinase signaling from all known VEGF receptors. Methods: This was an open-label, multi-center, phase I study to characterize the safety, tolerability, and pharmacokinetic (PK) profile of PTK/ZK, administered once daily at a dose of 750 mg or 1250 mg in adults with unresectable HCC. Pts previously treated with surgery, chemotherapy or radiotherapy were eligible. Pts were stratified into three groups based on total bilirubin and AST/ALT levels. Pts in Group 1, 2, 3 had mild, moderate and severe hepatic dysfunction respectively. PK data were collected from all Pts on days 1, 28, and 56. The primary endpoints were safety, tolerability of PTK/ZK, and the effects of hepatic dysfunction on the PK of PTK/ZK. Results: 34 Pts were enrolled, 21 in Group 1; 8 in group 2; and 5 in group 3. In all groups the most frequently reported adverse events (AEs) were vomiting, nausea, diarrhea, fatigue, anorexia and dizziness. A correlation between these AEs and the study drug dose was not observed. In Group 1, 2 of 4 Pts who received the 1250mg/d dose experienced DLTs (CTC grade 3 fatigue & CTC grade 4 elevation of AST). Two of the 6 Pts who received the 1000 mg/d dose experienced DLTs (ALT over 1.5X baseline and fatal hepatic tumor hemorrhage). No DLTs were observed at the 750mg/d dose, defined as the maximal tolerated dose (MTD) in Pts who have mild hepatic impairment. It was decided not to escalate above 750 mg/d in the other two groups. PK analysis indicated that there was no accumulation of PTK/ZK. Biologically active levels of PTK/ZK can be reached at a dosage of 750 mg/d. TTP in Pts who completed the trial ranged from 42 to 415 days. Of Pts in all groups,18 were evaluable for tumor response. No CR or PR was observed. 9 Pts had a best response of stable disease and 9 had progressive disease. Conclusion: 750 mg/d PTK/ZK is well tolerated in Pts with HCC and various degrees of hepatic impairment. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Jenapharm, Novartis, Schering AG
Addition of bevacizumab to first-line FOLFOX4 and overall survival in patients with metastatic colorectal cancer.
Authors: Mitsukuni Suenaga, Satoshi Matsusaka, Nobuyuki Mizunuma, Eiji Shinozaki, Mariko Ogura, Masato Ozaka, Koichi Takagi, Toshiharu Yamaguchi, Kiyohiko Hatake
Journal: Journal of Clinical Oncology (2012)

610 Background: In our previous report, addition of bevacizumab (BV) to the FOLFOX4 regimen appeared to significantly improve response rate, progression-free survival and overall survival in first-line treatment for patients with metastatic colorectal cancer (mCRC) (Suenaga M, et al. ASCO-GI 2011 [abstr 588]). Update results met median overall survival, and statistical analysis of survival was performed. Methods: An observational cohort study was carried out on all eligible patients scheduled to receive FOLFOX4 (n = 128) or FOLFOX4+BV (n = 85) between 2005 and 2007, 2007 and 2009, with a median follow-up time of 20.4 months vs. 30.2 months, respectively. Predefined efficacy endpoints were treatment characteristics, response rates, progression-free survival, and overall survival in the periods of time observed. Results: Median progression-free survival was 9.9 months (95% CI, 8.4-11.4) in the FOLFOX4- and 17 months (95% CI, 11.8-22.3) in the FOLFOX4+BV-treated patients (p=0.002). Median overall survival times were 20.5 months (95% CI, 16.9-24) and 38.8 months (95% CI, 32.9-44.8) in the two groups, respectively (p&lt;0.001). In the ECOG PS 0 population, progression-free survival in the FOLFOX4 and FOLFOX4+BV groups was 11 months and 17 months with a hazard ratio of 0.63 (95% CI, 0.44-0.89) in favour of FOLFOX4+BV, similarly in OS with a hazard ratio of 0.53 (95% CI, 0.36-0.77). Subgroup population received 5-FU plus leucovorin (FL) as maintenance during oxaliplatin discontinuation due to adverse events had longer PFS or OS in both groups, though no significance. PFS were 14.7 and 21.6 months, and OS were 29 and 45.9 months, respectively. Secondary resection was performed more in FOLFOX4+BV (11.8%) than FOLFOX4 (3.9%) patients. Conclusions: These data indicate potential survival benefits from the addition of BV to the FOLFOX4 regimen as first-line treatment for mCRC. Maintenance using FL after discontinuation of oxaliplatin due to adverse events appeared to be an essential factor for better survival.
Clinical Experience during the Paediatric Undergraduate Course
Authors: S F Ahmed, I A Hughes
Journal: Journal of the Royal Society of Medicine (1999)

Medical students at the Cambridge Clinical School are provided with a list of 42 core conditions they should encounter and 20 core skills they should perform during their attachment. By self-completion questionnaires we assessed their clinical experience and the amount of teaching they received, relating the results to marks gained in end-of-attachment assessments. 103 (93%) of 110 students in year one and 123 (96%) of 128 in year two completed the questionnaires. Of the 42 core conditions, 13 were seen by under 70% of the students in year one. In year two, exposure rate increased for 26 core conditions by a median of 7% (range 2-40) and decreased in 13 core conditions by a median value 4% (range 5-13) (P = 0.0005, chi 2). Only mandatory core skills were performed by over 90% of students. 5% of students did not perform any newborn examinations and under 60% observed neonatal resuscitation or a high-risk delivery. Students' core condition score was associated with their core skill score (r = 0.5), hospital grade (r = 0.3) and exposure to acute paediatrics (r = 0.3) (P < 0.005). There was no significant association between clinical experience and the objective examination score or the amount of teaching received. There was an inverse association between the number of students at a hospital and the number of core conditions with an exposure rate above 70% at that hospital (r = 0.7, P < 0.05). This study suggests that clinical experience may be better judged by the clinical supervisor than by assessment of theoretical knowledge.
Abstract 21152: Prognostic Utility of Exercise Treadmill Test in Women Is Enhanced by Application of Non-Electrocardiographic Exercise Test Variables
Authors: Ezra A Amsterdam, Brittany M Chatterton, Vunghi Hoang
Journal: Circulation (2010)

Objective: The limited diagnostic accuracy of the exercise treadmill test (ETT) in women with chest pain has promoted more costly stress imaging in this population. We hypothesized that non-ECG variables of ETT could enhance the utility of ETT in women. Methods: We evaluated ETT in women referred for chest pain from 9/96 to 10/03 who had a normal electrocardiogram and no cardiovascular disease (CVD). Longterm course (all-cause mortality) and CVD morbidity (myocardial infarction, heart failure, revascularization, stroke) was analyzed in relation to ETT results. Results: ETT were analyzed in 1,000 women (53.5 ± 10.8 y.o., 24-85). Follow-up was 6.4 ± 2.4 yr, mortality = 2.4% (0.4%/yr), morbidity = 7.9% (1.2%/yr), mortality + morbidity = 9.8% (1.5%/yr). Diagnostic ETT (≥85% maximum predicted heart rate [MPHR]) was achieved in 96.1% (961/1000). ETT was negative (NEG) (<1.0 mm horizontal ST↓ [ST↓]) in 79.1% (791/1000); positive (POS) (≥1.0 mm ST↓) in 17.0% (170/1000); nondiagnostic (ND) (no ST↓, <85% MPHR) in 3...
Doctors Need Doctors Too
Authors: Ranjana Srivastava
Journal: JAMA (2006)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal