tbuckley/cabot-search huggingface dataset:
Risk of Malignant Arrhythmias in Initially Symptomatic Patients With Wolff-Parkinson-White Syndrome
Authors: CarloPappone, GabrieleVicedomini, FrancescoManguso, MarioBaldi, AlessiaPappone, AndreaPetretta, RaffaeleVitale, MassimoSaviano, CristianoCiaccio, LuigiGiannelli, ZarkoCalovic, LuigiTavazzi, VincenzoSantinelli
Journal: Circulation (2012)

Background—The available amount of detailed long-term data in patients with Wolff-Parkinson-White syndrome is limited, and no prospective electrophysiological studies looking at predictors of malignant arrhythmia are available. Methods and Results—Among 8575 symptomatic Wolff-Parkinson-White patients with atrioventricular reentrant tachycardia referred for electrophysiological test, 369 (mean age, 23±12.5 years) declined catheter ablation and were followed up. The primary end point of the study was to evaluate over a 5-year follow-up the predictors and characteristics of patients who develop malignant arrhythmias. After a mean follow-up of 42.1±10 months, malignant arrhythmias developed in 29 patients (mean age, 13.9±5.6 years; 26 male), resulting in presyncope/syncope (25 patients), hemodynamic collapse (3 patients), or cardiac arrest caused by ventricular fibrillation (1 patient). Of the remaining 340 patients, 168 (mean age, 34.2±9.0 years) remained asymptomatic up to 5 years, and 172 (mean age, 13.6±5...
The Health Innovation We Need
Authors: Dave A. Chokshi
Journal: JAMA (2018)

According to NIFLA, CPCs also attract more women when they begin offering ultrasounds.Crisis pregnancy center efforts to obtain medical clinic status by incorporating sonography are being funded in part by grants from conservative Christian organizations such as Focus on the Family, based in Colorado Springs, Colorado.Nurses and directors from pregnancy centers can train at NIFLA's Institute in Limited Obstetric Ultrasound, which, the organization says, follows guidelines from the American College of Obstetricians and Gynecologists (ACOG) and the American Institute of Ultrasound in Medicine (AIUM).While spokespersons for ACOG and the ultrasound medicine organization declined to comment about pregnancy centers and their use of limited obstetric ultrasound, they did point out information on their organizations' websites that suggests the centers are not adhering to professional guidelines."A limited examination is performed when a specific question requires investigation," according to ACOG's ultrasound guidance."It does not replace a standard examination."
Perioperative Management of Dabigatran
Authors: Sam Schulman, Marc Carrier, Agnes Y.Y. Lee, Sudeep Shivakumar, Mark Blostein, Frederick A. Spencer, Susan Solymoss, Rebecca Barty, Grace Wang, Nancy Heddle, James D. Douketis
Journal: Circulation (2015)

The perioperative management of dabigatran in clinical practice is heterogeneous. We performed this study to evaluate the safety of perioperative management of dabigatran using a specified protocol.Patients treated with dabigatran and planned for an invasive procedure were eligible for inclusion. The timing of the last dose of dabigatran before the procedure was based on the creatinine clearance and procedure-related bleeding risk. Resumption of dabigatran was prespecified according to the complexity of the surgery and consequences of a bleeding complication. Patients were followed up for 30 days for major bleeding (primary outcome), minor bleeding, arterial thromboembolism, and death. We included 541 cases: 324 procedures (60%) with standard risk of bleeding and 217 procedures (40%) with increased risk of bleeding. The last dose of dabigatran was at 24, 48, or 96 hours before surgery according to the protocol in 46%, 37%, and 6%, respectively, of the patients. Resumption was timed according to protocol in 77% with 75 mg as the first dose on the day of procedure in 40% of the patients. Ten patients (1.8%; 95% confidence interval, 0.7-3.0) had major bleeding, and 28 patients (5.2%; 95% confidence interval, 3.3-7.0) had minor bleeding events. The only thromboembolic complication was transient ischemic attack in 1 patient (0.2%; 95% confidence interval, 0-0.5), and there were 4 deaths unrelated to bleeding or thrombosis. Bridging was not used preoperatively but was administered in 9 patients (1.7%) postoperatively.Our protocol for perioperative management of dabigatran appears to be effective and feasible.
Abstract 17771: Novel Ventricular Voltage Mapping Methodology With Omnipolar Electrograms
Authors: Karl Magtibay, Stephané Massé, John Asta, Andreu Porta-Sanchez, Shouvik Haldar, Daniel Malebranche, D. Curtis Deno, Kumaraswamy Nanthakumar
Journal: Circulation (2016)

Introduction: Variations in bipolar electrogram (EGM) voltage peak-to-peak (Vpp) due to the orientation of bipolar electrodes produce ambiguous bipolar voltage maps. This could lead to erroneous characterization of a myocardium and thus treatment strategy. Using omnipolar EGMs, we can mathematically determine an equivalent bipolar EGM and its Vpp (OTmax) along a wavefront angle-of-incidence (AOI) which, in concept, is the largest bipolar Vpp measurable in any orientation. OTmax can be used to standardize voltage mapping. Methods: We electrically mappped on four rabbit and two human ventricles using different 2D high density electrode arrays (HD grid and HD plaque). We calculated bipolar EGMs and Vpps from adjacent electrodes in two orientations, horizontal (H) and vertical (V). Bipolar voltage maps were created. To compare, we calculated OTmax within an area enclosed by 4 adjacent electrodes with which we used to create standardized bipolar voltage maps. We quantified both Vpp distributions and consistenc...
Essential Role of PDGFRα-p70S6K Signaling in Mesenchymal Cells During Therapeutic and Tumor Angiogenesis In Vivo
Authors: NorifumiTsutsumi, YoshikazuYonemitsu, YasunoriShikada, MitsuhoOnimaru, MitsuguTanii, ShinjiOkano, KazuhiroKaneko, MamoruHasegawa, MakotoHashizume, YoshihikoMaehara, KatsuoSueishi
Journal: Circulation Research (2004)

Discovery of the common and ubiquitous molecular targets for the disruption of angiogenesis, that are independent of the characteristics of malignant tumors, is desired to develop the more effective antitumor drugs. In this study, we propose that the platelet-derived growth factor receptor-α (PDGFRα)-p70S6K signal transduction pathway in mesenchymal cells, which is required for functional angiogenesis induced by fibroblast growth factor-2, is the potent candidate. Using murine limb ischemia as a tumor-free assay system, we demonstrated that p70S6K inhibitor rapamycin (RAPA) targets mesenchymal cells to shut down the sustained expression of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), via silencing of the PDGFRα-p70S6K pathway. Irrespective of the varied expression profiles of angiogenic factors in each tumor tested, RAPA constantly led the tumors to dormancy and severe ischemia in the time course, even associated with upregulated expression of VEGF from tumors. Because RAP...
Endothelial Modulation of β-Adrenergic Dilation of Large Coronary Arteries in Conscious Dogs
Authors: BijanGhaleh, Marie-LuceBéa, Jean-LucDubois-Randé, Jean-FrançoisGiudicelli, LucHittinger, AlainBerdeaux
Journal: Circulation (1995)

Background Endothelium-derived relaxing factors have been described as important intermediates in β-adrenergic vasodilation of resistance coronary vessels, but their involvement at the level of large epicardial coronary arteries remains controversial. Therefore, we examined the role of vascular endothelium in the β-adrenergic–mediated vasodilation of large epicardial coronary arteries in conscious dogs. Methods and Results Nine dogs were instrumented for measurement of left circumflex coronary artery diameter (CD) by sonomicrometry and coronary blood flow velocity (CBFv) with a Doppler technique in response to graded doses of isoproterenol (0.001 to 0.1 μg/kg IV bolus). Under control conditions, isoproterenol induced dose-dependent increases in CD and CBFv. When CBFv was kept constant at its baseline value by inflation of a cuff occluder, isoproterenol still induced dose-dependent increases in CD, but the latter were of lesser magnitude than those observed under normal CBFv conditions (110±20 versus 170±3...
Effect of Angiotensin on the Pressor Response to Tyramine in Normotensive Subjects and Hypertensive Patients
Authors: Yoshihirokaneko, Tadanaotakeda, Koujinakajima, Hideoueda
Journal: Circulation Research (1966)

Arterial blood pressure was recorded directly in 11 normotensive subjects, in 11 patients with essential hypertension and in 10 patients with renovascular hypertension. The pressor response to intravenous injections of norepinephrine, tyramine, angiotensin and ephedrine was compared in these three groups. An infusion of angiotensin was then given and the pressor response to injections of norepinephrine, tyramine, and ephedrine was again measured; in some cases, a comparison of the effects of the cold pressor test was made. In normotensive subjects, angiotensin infusion caused a significant increase in the responses to tyramine and ephedrine but not to norepinephrine; this occurred with subpressor doses and was unrelated to the level of blood pressure. In patients with renovascular hypertension, the mean pressor responses to injections of tyramine and ephedrine and the ratio of response to tyramine to that to norepinephrine were significantly increased, and the infusion of angiotensin failed to cause any f...
Abstract 3049: Dexamethasone pretreatment impairs the TS inhibition-mediated flare in thymidine salvage pathway activity
Authors: Sharyn I. Katz, Xiao Chen, Yizeng Yang
Journal: Cancer Research (2018)

Abstract Introduction: Inhibition of thymidylate synthase (TS) by pemetrexed, an inhibitor of thymidylate synthase, results in an early transient burst or “flare” in thymidine salvage pathway activity at 2 hrs of therapy, which, we have demonstrated in prior publications, can be measurable with FLT ([18F]thymidine)-positron emission tomography (PET) in non-small cell lung cancer (NSCLC). Administration of dexamethasone with pemetrexed-based therapy, as typically practiced in the clinic, could potentially confound this imaging approach since dexamethasone is known to inhibit expression of thymidine kinase 1, a key enzyme in the thymidine salvage pathway. Here we examine the potential impact of dexamethasone on the TS inhibition-mediated thymidine salvage pathway “flare” in NSCLC. Materials and Methods: In order to determine NSCLC cell line sensitivity to dexamethasone and pemetrexed, IC50 studies were performed on NSCLC cell lines H23, H1975, H460, H1299. TS inhibition-mediated “flare” in thymidine salvage pathway activity was then measured at 2hrs of exposure to pemetrexed and cisplatin in NSCLC cells lines following using 3H-thymidine incorporation assays under the following conditions: control (no chemotherapy or dexamethasone), treated with pemetrexed and cisplatin without dexamethasone, with 24 pretreatment of dexamethasone, or with dexamethasone administered together with chemotherapy. These conditions were chosen to model the delivery of pemetrexed-based therapy in the clinic. Results: The IC50 of H23, H1975, H460, H1299 for dexamethasone and pemetrexed were 40, 5.9, 718, 362 uM and 0.22, 0.73, 0.14 and 0.66 uM, respectively. Significant blunting of the thymidine salvage pathway “flare” is observed at 2hrs of pemetrexed-based therapy when dexamethasone-sensitive cell lines H23 and H1975 were pretreated with dexamethasone but not when dexamethasone was given together with pemetrexed therapy or in the setting of dexamethasone resistance (H460 and H1299). Conclusion: Imaging of TS inhibition may be impacted by pretreatment with dexamethasone but not administration of dexamethasone on the same day of therapy delivery. Citation Format: Sharyn I. Katz, Xiao Chen, Yizeng Yang. Dexamethasone pretreatment impairs the TS inhibition-mediated flare in thymidine salvage pathway activity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3049.
Expression, Genomic Organization, and Transcription of the Mouse Angiotensin II Type 2 Receptor Gene
Authors: ToshihiroIchiki, TadashiInagami
Journal: Circulation Research (1995)

Abstract Although the rat angiotensin II type 2 receptor (AT2) was cloned and shown to be a member of the seven transmembrane domain–type receptor family, its signaling mechanism and biological roles have not been established. To acquire additional information on the structure and functions of AT2 genomic DNA, we cloned the mouse AT2 gene and examined its expression, transcription, and genomic organization. The amino acid sequence of the mouse AT2 cDNA showed a 98.5% sequence identity with the rat AT2. In mouse fetus, mRNA of the AT2 was highly expressed in the eviscerated carcass and brain. This expression decreased rapidly after birth. In 10-week-old mice, mRNA of the AT2 could be detected in the brain by Northern blot analysis. However, reverse transcription–polymerase chain reaction showed that mRNA of the AT2 was expressed in all organs examined, indicating that the AT2 is expressed at a low level in other organs. Southern blot analysis of the genomic DNA of the mouse liver digested with BamHI, EcoRI...
Abstract 362: Dysregulation of CPT2 Splicing in Diabetic Heart Disease
Authors: ElizabethJaworski, CurtisNutter, SunilVerma, VaibhavDeshmukh, MugeKuyumucu-Martinez
Journal: Circulation Research (2014)

Diabetes mellitus is a group of metabolic diseases that are caused by elevated blood glucose levels. Individuals with diabetes have an increased risk of cardiovascular complications that include diabetic cardiomyopathy, hypertension, and coronary artery disease. Research has shown that hyperglycemia causes metabolic abnormalities in the heart such that cardiomyocytes are unable to utilize glucose for energy production due to reduced glucose intake, instead they solely depend on fatty acid oxidation for energy. Eventually, fatty acids accumulate and cause cardiac lipotoxicity, a presumed factor in the development of diabetic cardiomyopathy. Carnitine Pamitoyl Transferease 2 (CPT2) is one of the enzymes responsible for the transport of long-chain fatty acids into the mitochondria for fatty acid oxidation and energy production. CPT2 activity is elevated in diabetic hearts by mechanisms that are unclear. CPT2 is composed of 5 exons; the largest, exon 4 contains the transferase domain and is alternatively spli...
Intracardiac Echocardiography Is Superior to Conventional Monitoring for Guiding Device Closure of Interatrial Communications
Authors: ThomasBartel, ThomasKonorza, JawedArjumand, TikoEbradlidze, HolgerEggebrecht, GuidoCaspari, UlrichNeudorf, RaimundErbel
Journal: Circulation (2003)

Background— This study sought to test whether intracardiac echocardiography (ICE) is superior to conventional monitoring in guiding device closure of interatrial communications (atrial septal defect [ASD] and patent foramen ovale [PFO]). Methods and Results— Forty-four patients undergoing device closure of ASD (n=6) or PFO (n=38) were randomized to have the procedure guided by either ICE (group 1; n=22) or by transesophageal echocardiography (TEE) (group 2; n=22). All interventions were completed successfully. In 1 patient from group 2, atrial fibrillation occurred 1 day after device implantation; the patient was successfully cardioverted on the next day. There were no other complications. Fluoroscopy time (FT) (6.0±1.7 minutes versus 9.5±1.6 minutes; P<0.0001) as well as procedure time (PT) (33.4±4.7 minutes versus 37.8±5.6 minutes; P<0.01) were shorter in group 1 than in group 2. Group 2 patients required general anesthesia without (n=19) or with endotracheal intubation (n=3). In contrast, ICE allowed c...
n−3 Fatty Acid Supplementation for the Treatment of Dry Eye Disease
Authors: Penny A Asbell, Maureen G Maguire, Maxwell Pistilli, Gui-shuang Ying, Loretta B Szczotka-Flynn, David R Hardten, Meng C Lin, Roni M Shtein
Journal: New England Journal of Medicine (2018)

Dry eye disease is a common chronic condition that is characterized by ocular discomfort and visual disturbances that decrease quality of life. Many clinicians recommend the use of supplements of n-3 fatty acids (often called omega-3 fatty acids) to relieve symptoms.In a multicenter, double-blind clinical trial, we randomly assigned patients with moderate-to-severe dry eye disease to receive a daily oral dose of 3000 mg of fish-derived n-3 eicosapentaenoic and docosahexaenoic acids (active supplement group) or an olive oil placebo (placebo group). The primary outcome was the mean change from baseline in the score on the Ocular Surface Disease Index (OSDI; scores range from 0 to 100, with higher scores indicating greater symptom severity), which was based on the mean of scores obtained at 6 and 12 months. Secondary outcomes included mean changes per eye in the conjunctival staining score (ranging from 0 to 6) and the corneal staining score (ranging from 0 to 15), with higher scores indicating more severe damage to the ocular surface, as well as mean changes in the tear break-up time (seconds between a blink and gaps in the tear film) and the result on Schirmer's test (length of wetting of paper strips placed on the lower eyelid), with lower values indicating more severe signs.A total of 349 patients were assigned to the active supplement group and 186 to the placebo group; the primary analysis included 329 and 170 patients, respectively. The mean change in the OSDI score was not significantly different between the active supplement group and the placebo group (-13.9 points and -12.5 points, respectively; mean difference in change after imputation of missing data, -1.9 points; 95% confidence interval [CI], -5.0 to 1.1; P=0.21). This result was consistent across prespecified subgroups. There were no significant differences between the active supplement group and the placebo group in mean changes from baseline in the conjunctival staining score (mean difference in change, 0.0 points; 95% CI, -0.2 to 0.1), corneal staining score (0.1 point; 95% CI, -0.2 to 0.4), tear break-up time (0.2 seconds; 95% CI, -0.1 to 0.5), and result on Schirmer's test (0.0 mm; 95% CI, -0.8 to 0.9). At 12 months, the rate of adherence to treatment in the active supplement group was 85.2%, according to the level of n-3 fatty acids in red cells. Rates of adverse events were similar in the two trial groups.Among patients with dry eye disease, those who were randomly assigned to receive supplements containing 3000 mg of n-3 fatty acids for 12 months did not have significantly better outcomes than those who were assigned to receive placebo. (Funded by the National Eye Institute, National Institutes of Health; DREAM ClinicalTrials.gov number, NCT02128763 .).
Correction of Defective Interdomain Interaction Within Ryanodine Receptor by Antioxidant Is a New Therapeutic Strategy Against Heart Failure
Authors: MasafumiYano, ShinichiOkuda, TetsuroOda, TakahiroTokuhisa, HirokiTateishi, MamoruMochizuki, ToshiyukiNoma, MasahiroDoi, ShigekiKobayashi, TakeshiYamamoto, YasuhiroIkeda, TomokoOhkusa, NoriakiIkemoto, MasunoriMatsuzaki
Journal: Circulation (2005)

Background— Defective interdomain interaction within the ryanodine receptor (RyR2) seems to play a key role in the pathogenesis of heart failure, as shown in recent studies. In the present study we investigated the effect of oxidative stress on the interdomain interaction, its outcome in the cardiac function in heart failure, and the possibility of preventing the problem with antioxidants. Methods and Results— Sarcoplasmic reticulum (SR) vesicles were isolated from dog left ventricular (LV) muscle (normal or rapid ventricular pacing for 4 weeks with or without the antioxidant edaravone). In the edaravone-treated paced dogs (EV+), but not in the untreated paced dogs (EV−), normal cardiac function was restored almost completely. In the SR vesicles isolated from the EV−, oxidative stress of the RyR2 (reduction in the number of free thiols) was severe, but it was negligible in EV+. The oxidative stress of the RyR2 destabilized interdomain interactions within the RyR2 (EV−), but its effect was reversed in EV+....
Abstract 121: Angiogenin and the mmp9-timp2 axis are strongly upregulated in pro-angigoenic dnk-like cells isolated from colorectal cancer patients
Authors: Antonino Bruno, Giuseppe Pelosi, Luigi Boni, Lorenzo Dominioni, Lorenzo Mortara, Douglas Noonan, Adriana Albini
Journal: Cancer Research (2018)

Abstract Natural Killer (NK) cells are effector lymphocytes involved in tumor immunosurveillance. In solid malignancies, tumor associated (TANK; peripheral blood) and tumor infiltrating (TINK) NK cells have compromised functions. We functionally and molecularly characterize TINK and TANKs from blood and tissue samples of colorectal cancer (CRC) patients, a tumor type where inflammation and angiogenesis have clinical relevance, compared to NK isolated from control and non-oncologic inflammatory bowel disease patients. NK subset distribution and cytokine profiling were performed by multicolor flow cytometry, using peripheral blood and tissue samples from CRC patients, for surface antigen and cytokine profiling characterization. Conditioned media (CM) from FACS-sorted NKs were used either for secretomic profiling using antibody membrane arrays or in functional in vitro angiogenesis assays. CRC TINKs/TANKs showed decreased activation marker NKG2D, impaired degranulation activity, a decidual-like NK polarization toward the CD56brightCD16dim/- CD9+CD49+ subset. TINKs and TANKs supernatants induced endothelial cell proliferation, migration, adhesion and formation of capillary-like structures in vitro. It has been reported that dNK release proangiogenic factors and metastasis-associated (MMP-9, TIMP1-2) proteins. We describe for the first time the expression of angiogenin and MMP2, MMP9, TIMP1 and TIMP2 by CRC derived NK cells. This could be a phenotype relevant to their invasive capabilities and pro-angiogenic function. STAT-3/STAT-5 activation was observed in TANKs, and inhibition of the STAT5 pathway by pimozide, an antipsychotic drug, reduced proangiogenic factor VEGF and angiogenin production and capillary-like structure formation, but did not affect the levels of TIMP-1, TIMP-2 and MMP-9. Citation Format: Antonino Bruno, Giuseppe Pelosi, Luigi Boni, Lorenzo Dominioni, Lorenzo Mortara, Douglas Noonan, Adriana Albini. Angiogenin and the mmp9-timp2 axis are strongly upregulated in pro-angigoenic dnk-like cells isolated from colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 121.
Promoting Patient Interests in Implementing the Federal Right to Try Act
Authors: Holly Fernandez Lynch, Patricia J. Zettler, Ameet Sarpatwari
Journal: JAMA (2018)

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