tbuckley/cabot-search huggingface dataset:
Abstract 534: Large Tumor Suppressor 2 (Lats2), a Downstream Target of Mammalian Sterile 20 Like Kinase 1 (Mst1), Negatively Regulates Ventricular Mass.
Authors: Noritsugu Nakano, Yutaka Matsui, Junichi Sadoshima
Journal: Circulation (2007)

Mst1 is an evolutionarily conserved serine threonine kinase which is a critical regulator of growth and death in cardiac myocytes. Mst1 forms a complex with hWW45 and Lats2, thereby activating Lats2. Lats2 partially mediates the proapoptotic effect of Mst1 in cardiac myocytes in vitro . In order to elucidate the cardiac function of Lats2 in vivo , we generated transgenic mice with cardiac specific expression of Lats2 (Tg-Lats2, line #8) and dominant negative Lats2 (Tg-DN-Lats2). At 5– 6 months of age, Tg-Lats2 exhibited a greater left ventricular (LV) end-diastolic dimension (4.3 vs 3.7 mm, n = 8, n = 7, p &lt; 0.05) and lower LV ejection fraction (EF, 63 vs 72 %, p &lt; 0.05) than wild type (WT) mice. In addition, many Tg-Lats2 exhibited a remarkably enlarged right atrium with mural thrombus. Although LV weight /body weight (LVW/BW) in Tg-Lats2 was not significantly different from that in WT, right ventricular weight (RVW)/BW in Tg-Lats2 was significantly smaller than that in WT (0.65 vs 0.96, p &lt; 0.05). The LV myocyte cross sectional area (CSA) was significantly smaller in Tg-Lats2 than in WT (82 vs 100%, p &lt; 0.05) and the RV myocyte CSA showed a similar tendency. Significantly reduced RVW/BW and LVEF were also observed in Tg-Lats2 line #20 (milder expression). Tg-Lats2 exhibited greater levels of interstitial fibrosis (13.0 vs 3.4%, p &lt; 0.05) at baseline. Although the number of TUNEL positive myocytes was not different between Tg-Lats2 and WT at baseline, it was significantly greater in Tg-Lats2 after transverse aortic constriction for 4 weeks (0.12 vs 0.09%, p &lt; 0.05). In contrast, Tg-DN-Lats2 exhibited significantly greater LVW/BW (3.88 vs 3.27, n = 10, n = 10, p &lt; 0.05) and RVW/BW (0.96 vs 0.73, p &lt; 0.05), and normal LV function. Furthermore, adenovirally expressed Lats2 reduced both the relative cell size and protein/DNA content in cultured neonatal rat cardiac myocytes (53.5%, 63.2% vs LacZ control virus, n = 3, p &lt; 0.05). Conversely, DN-Lats2 virus transduction significantly increased the cell size and protein/DNA content of cardiac myocytes (125.0%, 121.1% vs LacZ control virus, n = 3, p &lt; 0.05). These results suggest that Lats2 is a critical negative regulator of ventricular mass and that stimulation of Lats2 leads to increases in cell death, fibrosis and cardiac dysfunction.
Abstract 2765: Natural History and Genetic Features of Short QT Syndrome
Authors: Nicola Monteforte, Mirella Memmi, Raffaella Bloise, Elena Ronchetti, Carlo Napolitano, Silvia G Priori
Journal: Circulation (2008)

Short QT syndrome (SQTS) is a rare genetic disorder characterized by abnormally short QT interval and high risk of sudden cardiac death (SCD). This study addresses the issue of natural history, genetics and electrocardiographic features in the largest prospective SQTS cohort (47 individuals in 24 families). Diagnosis was made in the presence of QTc interval ≤ 350 ms w./out history of cardiac arrest (CA) or SCD without structural abnormalities. Median age at diagnosis was 27 years (range 4–56); mean QTc was 323±17 ms, 22/36 (61%) pts had abnormal T wave (n=17) and/or J point elevation (n=8) and/or QRS slurring (n=3); at a mean observation time of 30±14 years, 22 (47%) pts had cardiac events: 11 SCD, 4 resuscitated CA and 7 syncopal episodes. Median age at SCD or CA was 19 (range 0 – 48) years (4 death/CA occurred in the first year of life). The Kaplan Meyer curve shows survival-free interval before drugs. Triggers for the 15 death/CA were exercise (44%) and rest (56%). Eight pts were treated with quinidine (250 mg bid) that prolonged QTc: from 320±18 ms to 380±18 ms (p&lt;0.005). Genetic screening on KCNH2, KCNQ1 and KCNJ2 genes was positive in 3/24 probands and 3 family members. Interestingly, genotyped pts (n=6) presented significantly shorter QTc than non-genotyped pts (303±13 ms vs. 328±14 ms, p&lt;0.001). In summary our data show that SQTS is a severe disorder with high risk of cardiac arrest occurring from infancy to adulthood. The yield of genetic testing is low (13%) suggesting genetic heterogeneity, but patients harboring a genetic mutation have more severe phenotype. The use of quinidine can help to normalize the QTc although its effect on cardiac events remains to be assessed.
Abstract 18181: Predictors of Success for Percutaneous Coronary Intervention of Chronic Total Occlusions: a Consecutive Series of 1,500 Patients
Authors: Tora Leong, Philippe Garot, Yves Louvard, Talal Harb, Thierry Unterseeh, Thomas Hovasse, Hakim Benamer, Marie-Claude Morice, Bernard Chevalier, Thierry Lefevre
Journal: Circulation (2012)

Introduction & Hypothesis .  Percutaneous Coronary Intervention (PCI) of chronic total occlusions  (CTOs) remains challenging in terms of indication and technique.  Newer techniques continue to develop that may improve safety and the  rate of success. We aim to examine factors that may predict success  in order to improve patient selection and acute results.   Methods & Results . Of 1,508 consecutive PCIs of  CTO in our institution performed between January 2004 and January  2012, the success rate was 71%. Operator experience was defined as  the number of cases performed. Patients were 63.5±11.3 years  old, 86% male, creatinine 98±65 μmol/L, previous CABG 8%,  previous MI 23%, previous PCI 39%, lesion length 20±17 mm. Definite CTO age was known only in 17.9% of cases and the mean CTO age was 26±46 months. Radial approach was used in 82% of cases, procedural duration was 92±50 min and amount of contrast media was 280±171 ml. In hospital outcome was as follows: access site complication 0.4%, hemoglobin drop >5 g/dL 0.07%, peri-procedural MI 0.33%, emergency CABG 0.27%, pericardiocentesis 0.81% and death 0.99%. The table summarizes the predictors of success by univariate and multivariate analyses.   Conclusions . In this contemporary series, the traditional factors of lesion length, calcification, stump visibility and proximal tortuosity remain highly robust predictors, as well as other anatomical and clinical factors such as previous MI and previous CABG. The presence of intraluminal channel and operator’s experience also significantly contribute to success. Table 1
Abstract 3369: Association Between Bi-directional Mitral Isthmus Block and Atypical Flutter Following Left Atrial Linear Ablation in Patients with Symptomatic Atrial Fibrillation
Authors: Ramtin Anousheh, Navinder Sawhney, Charles Tate, Michael Panutich, Wayne Whitwam, Gregory Feld
Journal: Circulation (2007)

Background: Incomplete or unidirectional mitral isthmus block (MIB) during left atrial linear ablation (LALA) for atrial fibrillation (AF) may be proarrhythmic, and is the most common target for repeat ablation in patients with atypical atrial flutter (AAFL) after LALA. Objective: To determine if achieving bidirectional MIB during LALA will reduce occurrence post-ablation AAFL and/or recurrence of AF. Methods and Results: Fifty-six consecutive patients (pts), 49 males and 7 females, mean age 59±8 years, who underwent LALA for symptomatic, persistent (61%) or paroxysmal (39%) AF were evaluated. Thirty-four pts had been previously ablated, none had MIB from the first ablation. All pts underwent LALA including two encircling lesions around the right and left pulmonary veins, a line at the roof of the left atrium between the two circles, and a line from the lateral mitral valve annulus (MVA) to the left circle with adjunctive coronary sinus ablation as needed to achieve MIB. Thirty pts had an additional line from the septal MVA to the right circle. Bi-directional MIB was documented by pacing from the left atrial appendage and proximal coronary sinus. Bi-directional MIB was achieved in 38 pts (68%), with ablation in the coronary sinus required in 87.5% of pts. Thirty-seven pts underwent LALA with a standard 8 mm tip (Blazer™ or Navistar™) catheter and 19 pts with saline-irrigated catheters (ThermoCool™, Chili™). Patients were followed for 6±2 months. AAFL occurred in 15 pts (27%), and 17 pts (30%) had recurrence of AF. In pts with AAFL, 8 had documented bi-directional MIB during ablation and 7 did not. The odds of AAFL was 7.6 times higher in pts without MIB compared those with MIB (p=0.02); adjusting for age, gender, diagnosis, type of catheter, coronary sinus ablation and history of previous ablation. This study did not show similar association between recurrence of AF and MIB (p=0.5). Conclusions: Achieving bi-directional MIB will reduce incidence of post-ablation AAFL significantly. Recurrence of AF is not reduced by achieving bi-directional MIB.
Abstract 1841: Volumetric 3D Echo vs 3D-Guided Biplane 2D Echo for Measurements of LV Parameters
Authors: Carly Jenkins, Jonathan Chan, Lizelle Hanekom, Thomas H Marwick
Journal: Circulation (2006)

Background: Accurate measurement of LV volumes is a major potential attraction of 3D echo (3DE). In pts with resting wall motion abnormalities, when geometric assumptions of 2DE may not apply, it i...
Abstract 9746: Differential Impact of Dose-Related Chronic Alcohol Ingestion on Action Potential Upstroke, Systolic Myocardial Function and Cardiac Pro-inflammatory Factors mRNA Expression in Male C57BL/6 Mice
Authors: Chung-Lieh Hung, Yu-Jun Lai, Ting-Yi Tien, Ya-Ming Tseng, Cheng-I Lin, Yao-Chang Chen, Hung-I Yeh
Journal: Circulation (2011)

Background Cardiomyopathy elicited by ethanol or the toxic metabolites after chronic excessive alcohol intake had been well documented. However, to what extent of such dose-related chronic alcohol (Alc) ingestion on myocardial systolic performance and electrical disturbance remained unclear. Methods Totally 40 C57BL/6 male mice of 6 weeks old were fed with a liquid diet containing 4% (n=13) or 6% (n=14) alcohol and normal diet (CTRL, n=13) for 12 weeks. In vivo cardiac function was examined by echocardiography at baseline and before animal sacrifice. Optical mapping (Lecia MZ FLIII system, Heidelberg, Germany) and single cardiomyocyte patch clamp were used to assess conduction velocity of ventricular surface and action potential of single cardiomyocyte, respectively. Extent of myocardial macrophage infiltration and fibrosis were examined by immunostaining with the mRNA content of pro-inflammatory factors determined by real-time PCR. Results Both 4% and 6% Alc groups had reduced conduction velocity (47±3 cm/s and 28±8 cm/s vs Ctrl: 71±7 cm/s, p&lt;0.05)) and a more perturbated activation spread. Echocardiography demonstrated enlarged cardiac dimension and worsened fractional shortening in both Alc groups while only 6% Alc mice demonstrated a significant decline of systolic myocardial velocity (Ctrl vs 6%: 1.14±0.03 vs 0.97±0.03, p&lt;0.05). Reduced action potential upstroke velocity (Figure) and abnormal resting membrane potential were shown in both Alc groups. Markedly increased macrophage infiltration and fibrosis zone (6% vs Ctrl: 3.1±0.3 vs 1.3±0.1 mm 2 /cm 2 , p&lt;0.05) were accompanied by significantly elevated pro-inflammatory (including TNF-α, ΙL-6, and ΜΜP-2) factors mRNA expression only in 6% Alc mice. Conclusion These results showed a differential impact of myocardial electromechanical disturbance in response to dose-specific Alc ingestion and that overt inflammation response may start to take place in more severely damaged myocardium.
Abstract 2451: Increased Myocardial Sensitivity to IKr Inhibition in Patients With Heart Failure Due to Left Ventricular Systolic Dysfunction
Authors: James E Tisdale, Brian R Overholser, Kevin M Sowinski, Heather A Wroblewski, Kwadwo Amankwa, Steven Borzak, Joanna R Kingery, Rita Coram, Douglas P Zipes, David A Flockhart, Richard J Kovacs
Journal: Circulation (2009)

Introduction:  Patients with heart failure (HF) are at increased risk of drug-induced torsades de pointes (TdP).   Hypothesis:  Myocardial sensitivity to I Kr  inhibition is enhanced in patients with HF due to left ventricular (LV) systolic dysfunction   Methods:  Patients (n=15) with atrial fibrillation or atrial flutter requiring conversion to sinus rhythm; n=6 with NYHA class II–III HF [mean LV ejection fraction (LVEF) 30±9%], and n=9 controls [mean LVEF 54±5%]. Patients with electrolyte abnormalities or receiving other QT-prolonging drugs were excluded. Patients were administered intravenous ibutilide 1mg over 10 minutes. Blood samples and three 12-lead ECGs were obtained prior to and post-infusion and at 5, 15, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 48 hours post-infusion. Serum ibutilide concentrations were determined and Fridericia-corrected QT (QT F ) intervals were measured from leads II, V1, and V5. The majority of (77%) post-infusion QT intervals were obtained in sinus rhythm. Sensitivity to I Kr  inhibition was expressed as ibutilide concentration at 50% maximum effect on QT F  (EC 50 ). Exposure to QT F  interval prolongation was assessed by area under the QT F  interval-time curves (AUEC).   Results:  Ibutilide pharmacokinetics in the two groups were not significantly different. Ibutilide concentration- QT F  effect relationships were best described by a sigmoidal E max  model with a hypothetical effect compartment. The predictive power of the model for concentration-effect relationships was best using the maximum QT F  measured across the three leads vs the corresponding ibutilide concentration (R 2 =0.82). AUEC from 0 – 4 hours was larger in the HF group (Table). EC 50  was lower in the HF group, indicating that a lower serum ibutilide concentration was required to prolong QT F  interval to 50% maximum.  Conclusions: Myocardial sensitivity to I Kr  inhibition is enhanced in patients with systolic HF, which may contribute to the increased risk of drug-induced TdP.  This research has received full or partial funding support from the American Heart Association, Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota & Wisconsin).
Abstract 2985: Lipoprotein, Blood Pressure and Stroke Risk: Findings from the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Study
Authors: Pierre Amarenco, Larry B Goldstein, Michael Szarek, Amy E Rudolph, K M Welch, Investigators
Journal: Circulation (2006)

Introduction: The SPARCL trial showed significant reductions in the risk of stroke (16%) and major coronary events (MCE, CHD death, non-fatal MI and resuscitated cardiac arrest, 35%) in patients wi...
Abstract 18212: Masked Hypertension is Frequent in Obstructive Sleep Apnea Syndrome and not Associated with its Severity
Authors: Franck Boccara, catherine meuleman, Louise Boyer Chatenet, Sylvie Lang, Fanny Douna, Emmanuelle Berthelot, Xuan-Lan Nguyen, Stephane Ederhy, Ghislaine Dufaitre, Bernard Fleury, Ariel Cohen
Journal: Circulation (2010)

Background: The prevalence of masked arterial hypertension seems to be high in patients with Obstructive Sleep Apnea Syndrome (OSAS). MH has been associated with a higher risk of cardiovascular eve...
Abstract 17010: The Coronary Arteries Chronic Total Occlusion Recanalization Reduces Symptoms in Patients with Stabile Angina in Short- and Long-Term Observation
Authors: Milosz J Jaguszewski, Marcin Fijalkowski, Radoslaw Targonski, Lukasz Lewicki, Michal Chmielecki, Witold Dubaniewicz, Dariusz Ciecwierz, Andrzej Rynkiewicz
Journal: Circulation (2011)

Objectives: Despite the ongoing technological progress and the introduction of more advanced equipment, chronic total occlusions (CTO) remains a challenge. Technical difficulties imply higher exposure to contrast media and radiation but clinical benefits of this procedure are not well defined. The goal of the study was to assess the influence of a successful recanalization of the coronary arteries chronic total occlusion on the reduction of angina symptoms and risk of major cardiovascular events (death, myocardial infarction, further revascularizations) in stable ischemic heart disease. Methods: The study group consists of 401 patients (72.8% men), age 65.5±10.0 years, who underwent the PCI of the CTO in I Department of Cardiology, Medical University of Gdansk, Poland. We analyzed frequency of major adverse cardiac events (MACE) and CCS angina class in patients with successful procedure (group 1) and failure (group 2). The data from the 6-months and 18-months follow up was collected over the phone calls and clinical visits. Results: There was significant difference in the prevalence of the angina symptoms between both groups in 6-month follow up (group 1 vs. group 2: 178 vs. 33, p&lt;0.01) and 18-month observation (group 1 vs. group 2: 145 vs. 11, p&lt;0.05). Moreover, the patients with ineffective recanalization of the CTO had to undergo the CABG much more often than the patients with effective recanalization in 6- and 18-months follow up (4.2% vs. 0,4%, p&lt;0,01 and 9.1% vs. 1.2%, p&lt;0,01, respectively). However there were no differences between the group 1 and group 2 in death, myocardial infarction and TVR or TLR frequency in 6-month follow up (respectively: 0 vs. 0; 2.3% vs. 1.4%; 13.6% vs.11.2%, all p=NS) and 18-month follow up (respectively: 1.9% vs. 2.1%; 3.9% vs. 2.8% and 23.6% vs. 14.7%, all p=NS). Conclusions: Successful recanalization of the coronary arteries CTO considerably decrease angina intensity. The patients with the successful recanalization of the CTO had less frequent CABG. There is no influence of CTO recanalization results on the mortality, risk of myocardial infarction and new revascularizations during 6- and 18-month observation.
Brucellosis or Bang's Disease of Farm Animals
Authors: C. P. Fitch, W. L. Boyd
Journal: JAMA (1941)

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
Modified FOLFIRINOX as initial treatment of advanced pancreatic cancer: A single cancer center experience.
Authors: Michal Vocka, Zdenek Krska, David Hoskovec, Josef Horejs, Lubos B. Petruzelka
Journal: Journal of Clinical Oncology (2015)

e15228 Background: The FOLFIRINOX regimen has been shown to significantly increase both overall (OS) and progression free (PFS) survival in metastatic pancreas cancer (MPC), compared to gemcitabine. However this regimen is associated with significant toxicity. The purpose of our analysis was to evaluate the efficacy and safety of modified FOLFIRINOX with 25% dose reduction of oxaliplatin, irinotecan and 5-fluorouracil administered every 2 weeks without profylactic growth factors in pacient with advanced pancreatic adenocarcinoma. Methods: A retrospective analysis was conducted on all patients treated with modified FOLFIRINOX for advanced pancreatic cancer between January 2013 and December 2014. The primary objective was to evaluate the efficacy and safety of FOLFIRINOX when used with dose modifications. Toxicity was graded as per CTCAE version 4.0. Results: A total of 26 patients were identified (10 locally advanced, 16 metastatic). The median age was 61,6 (range 43-69) and at baseline all patients had an ECOG performance status of 0 or 1 (46% and 54% respectively). The primary tumour was located in the head of the pancreas in 46% of patients and 19% of patients had a biliary stent. The median number of FOLFIRINOX cycles administered was 8,5 (range 2-19) but 15% of patients currently remain on treatment. Response rate was 38% (all achieved a partial response) and 19% achieved stable disease. Three patients (11,5%) with locally advanced pancreatic cancer became suitable for curative surgical resection following chemotherapy. The median PFS was 7,3 month (in locally advanced 7,95 months and in metastatic 7,02 months). The median overall survival was 17,54 months (in locally advanced 16,96 months and in metastatic 17,86 months). The treatment was very well tolerated without neutropenia G3/4 or febrile neutropenia. Grade 3/4 non-hematologic AEs were observed in 25% of pts, including vomiting (15%), nausea (11%) and diarrhea (7%). Conclusions: In patients with advanced pancreatic cancer in good performance status (0-1) FOLFIRINOX may lead to a significant prolongation of time to progression and overall survival with good quality of life even with dose reduction.
Abstract 4666: Anatomic Substrate as Determinant of Dominant Frequency Dynamics During Human Ventricular Fibrillation
Authors: Karthikeyan Umapathy, Stephane Masse, Elias Sevaptsidis, John Asta, Talha Farid, Elnaz Shokrollahi, Krishnakumar Nair, Heather Ross, Terry Yau, Robert Cusimano, Sridhar Krishnan, Kumaraswamy Nanthakumar
Journal: Circulation (2008)

Background: Dominant frequency (DF) analysis is a common way of quantitatively studying the spatio-temporal variation of frequency during VF. Areas of high frequencies (e.g. rotors) and low frequencies (e.g. blocks) have been associated with the occurrence and maintenance of VF. However, the relation of these high or low frequency areas to anatomical or physiological substrate remains unclear. Objective: We tested the hypothesis that the Max-Min DF locations in the epicardium during VF are due to anatomical substrate. Methods and Results: We analyzed 33, 4 seconds VF episodes acquired from 6 isolated human hearts using a Langendorff setup. The hearts were received from the heart-transplanted patients with informed consent. Electrode array consisting 112 bipolar electrodes was used to acquire the surface unipolar and bipolar electrograms from the epicardium. DF was computed as the peak frequency of the VF segment from each of electrodes using Welch’s modified periodogram method. From the DF distribution, the regions of max and min frequencies were identified for LV and RV regions. Scar maps were computed for each of the 6 hearts using a previously published method by mapping the amplitude of bipolar electrograms (&lt;0.5mv = scar) during the pacing protocol. The areas of max-min DF frequencies in each of the VF episode were compared to the corresponding spatial locations in the scar map. Table 1 shows the match between the max-min DF frequency locations and the scar locations. 50% of max-min DF frequencies locations match the scar locations and in 97% of the matched locations the max-min DF occur at the vicinity of the scar. Conclusion: During human VF, DF dynamics are only partially explained by the anatomical substrate. This suggests that ion channel heterogeneity and dynamic physiological factors may play an important role in determining fibrillation dynamics. Match Between Max-Min DF locations and Scar Locations