tbuckley/cabot-search huggingface dataset:
Abstract 17454: ADP Ribosyl Cyclase (CD38) Degrades the NADP(H) Pool Causing Endothelial Nitric Oxide Synthase Dysfunction in the Postischemic Heart
Authors: Levy A Reyes, Jay L Zweier
Journal: Circulation (2011)

In postischemic myocardium impaired endothelial function occurs with endothelial nitric oxide synthase (eNOS) dysfunction and this limits vasodilation and tissue perfusion. Recently, we have shown in the isolated rat heart, that during ischemia/reperfusion (I/R) injury both tetrahydrobiopterin (BH 4 ) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) are depleted, and when these lost eNOS cofactors/substrates are repleted the activity of the dysfunctional enzyme is largely restored and vasodilation markedly improved. In addition to its role as an obligatory NOS substrate, NADPH is also required for maintenance of BH 4 levels through dihydrofolate reductase. We observe that endothelial NADP(H) levels are &gt;80% depleted in reperfused hearts following 30 min of global ischemia and NADPH repletion yields a marked 30% increase in coronary flow. However, while NADPH repletion is highly beneficial, the pathway of its degradation was unknown. We show that following 30 min I and R, the oxidized form of NADPH, NADP + , falls in the whole heart tissue to 29% ± 1% of pre-ischemic levels and to less than 10% in the endothelium, which limits its availability to replenish NADPH in turn hindering vasodilation. We further show that the fall of NADP + coincides with the production of nicotinamide and 2-phospho-cyclic adenosine diphosphoribose (2-P-cADPR), a signaling molecule with the potential to liberate Ca 2+ via IP 3 pathway. These data suggest that the enzyme ADP Ribosyl Cyclase (CD38) is activated and depletes NADP + . Treatment with the CD38 inhibitor -NAD + enhanced the recovery of postischemic coronary flow. CD38 is known to be activated by oxidative stress. Thus, we observe that CD38 is activated in the postischemic heart and degrades the NADP(H) pool with production of cADPR which can induce release of Ca 2+ from intracellular stores. Thus, inhibition of CD38 provides a promising new approach to improve the recovery of endothelial function in the postischemic heart.
J-Point Elevation in Survivors of Primary Ventricular Fibrillation and Matched Control Subjects
Authors: Raphael Rosso, Evgeni Kogan, Bernard Belhassen, Uri Rozovski, Melvin M. Scheinman, David Zeltser, Amir Halkin, Arie Steinvil, Karin Heller, Michael Glikson, Amos Katz, Sami Viskin
Journal: Journal of the American College of Cardiology (2008)
Abstract 15222: Admission Glucose Level is a Risk Factor for 30-Day Mortality in Non-Diabetic Patients with Acute Myocardial Infarction but Glycosylated Hemoglobin Level is Not
Authors: Young Jin Youn, Ji Hyun Lee, Jun-Won Lee, Sung-Gyun Ahn, Min-Soo Ahn, Jang-Young Kim, Byung-Su Yoo, Seung-Hwan Lee, Junghan Yoon, Kyung-Hoon Choe
Journal: Circulation (2012)

Background -  Although acute hyperglycemia is associated with adverse outcome in non-diabetic patients with acute myocardial infarction (AMI), it is unclear whether this association is due to hyperglycemia as an acute stress response or long-term poor glycemic control. We evaluated whether acute (admission glucose) or chronic hyperglycemia (hemoglobin A1c [HbA1c]) is associated with in-hospital mortality in non-diabetic patients with AMI treated with percutaneous coronary intervention (PCI).   Methods and Results -  Consecutive 502 patients without history of diabetes mellitus presenting AMI were included. Both glucose and HbA1c were measured on admission. All patients were treated with PCI. Primary endpoint was 30-day mortality. Patients were divided into 4 groups according to the quartiles of glucose (median = 124.0 mg/dl, IQR 103.8 - 152.0) and HbA1c (median = 5.8%, IQR 5.6 - 6.2). Male was 75.3% and age was 65.1 ± 13.0 years. ST segment elevation myocardial infarction (STEMI) was 38.6% and non-STEMI was 61.4%. 30-day mortality was 1.6%, 3.4%, 3.1%, 13.7% according to the quartiles of glucose (p   Conclusion -  In non-diabetic patients with AMI, admission glucose level was associated with 30-day mortality but HbA1c was not. This result demonstrated that acute glycometabolic derangement rather than chronic hyperglycemia is associated with short-term mortality in these patients.
Stages of change model for smoking prevention and cessation in schools
Authors: J. O Prochaska
Journal: BMJ (2000)

<h3></h3> CT scanning of the chest, abdomen and pelvis (CT-CAP) is often used by neurologists to identify underlying disease processes such as malignancy or sarcoidosis. However, the utility of CT-CAP, and the rate of incidental findings, remains uncertain. This retrospective study investigated all CT-CAP requests by the neurology department in Edinburgh over a 5-year period (n=261), combining CT-CAP reports with electronic patient records. Incidental findings were classified by need for further investigations. Category 1 findings required further investigations (e.g. pulmonary nodule &gt;4 mm). Category 2 findings required extra tests depending on clinical context (e.g. dilated biliary tract; liver function and surgical history determining need for further investigations). Category 3 findings did not require further investigations (e.g. simple diverticular disease). 20% (n=51) of CT-CAP scans were reported as showing an underlying malignancy, with half (n=26) confirmed as cancer by subsequent investigations. CT-CAP identified three cases of sarcoidosis and one of tuberculosis. There were 191 category 3 incidental findings, 57 category 2 incidental findings, and 27 category 1 findings. Overall, CT-CAP shows an underlying cause of neurology symptoms in 11.5% of cases. The proportion of patients needing further tests due to category 1 or concerning category 2 incidental findings (12/57) was higher at 14.9%.
Abstract 8208: Scar Border and Transmural Core Defined by Magentic Resonance Imaging Contribute to T wave Alternans in Patients with Cardiomyopathy: Implications for Identifying Arrhythmogenic Substrate
Authors: Adrian M Suszko, Danna A Spears, Graham A Wright, Andrew M Crean, Arnold Pinter, Andrew T Yan, Joan Ivanov, Vijay S Chauhan
Journal: Circulation (2011)

BACKGROUND Structural barriers can lead to discordant action potential (AP) alternans in animal studies by slowing conduction and increasing AP gradients. We hypothesized that border zone and midwall scar will promote T wave alternans (TWA) in patients with cardiomyopathy by potentially slowing conduction and uncoupling transmural APs, respectively. METHODS AND RESULTS We prospectively studied 40 patients (53±14 yrs, LVEF 40±17%) with ischemic (n=12), dilated (n=12), or hypertrophic cardiomyopathy (n=16). Scar core and border zone were quantified as a percent of LV mass by applying signal-intensity thresholding to late gadolinium enhanced cardiac magnetic resonance images. The transmural distribution of core was determined from the short-axis LV slices and classified as endocardial, epicardial, midwall and full thickness core. TWA was evaluated during incremental atrioventricular pacing at 100, 110 and 120 bpm. TWA was quantified from ECG recordings using the spectral method and classified as positive if Valt &gt;1.9 µV and k &gt;3. +TWA was detected in 27 (68%) patients. The percentages of border zone, epicardial core and midwall core were greater in +TWA vs. - TWA. Maximum TWA magnitude correlated with the relative size of border zone (r=0.52, P&lt;0.001), epicardial core (r=0.54, P&lt;0.001) and midwall core (r=0.40, P=0.01). The heart rate onset for TWA (Valt &gt;0 µV, k &gt;3) was significantly lower in those patients with greater border zone and epicardial core. Multivariate analysis revealed border zone to be the only independent predictor of +TWA (Odds Ratio 1.22/10%, P=0.003). CONCLUSIONS In cardiomyopathy patients, scar border zone, epicardial core and midwall core contribute to +TWA. These structural barriers in the presence of +TWA may together provide a potent substrate for lethal ventricular arrhythmias.
Phase Ib study of PR-104, a hypoxia-activated alkylating agent, in combination with gemcitabine (G) or docetaxel (D) in patients with advanced cancer
Authors: N. S. Tchekmedyian, R. K. Ramanathan, M. J. McKeage, J. Rajendran, R. L. Korn, T. J. Melink, J. C. Gutheil, M. B. Jameson
Journal: Journal of Clinical Oncology (2008)

3575 Background: PR-104 is a prodrug with selective toxicity to hypoxic tumor cells. In these cells, PR-104 forms a nitrogen mustard alkylator causing DNA crosslinks. Preclinical data suggest additive efficacy for PR-104 combined with G or D. This study defines the toxicities, maximum tolerated dose (MTD) and pharmacokinetics (PK) of PR-104 in combination with either G or D, with or without GCSF. Methods: Patients (pts) had cancer for which G or D was considered reasonable treatment by the physician. All cohorts (>3 pts) received a fixed dose of G (800 mg/m2) or D (60 mg/m2) with escalating or de-escalating doses of PR-104 administered IV every 3 weeks (wks): Grp A=PR-104 (starting at 275 mg/m2) + G on days 1 and 8; Grp B=PR-104 (starting at 400 mg/m2) + D on day 1. Grp C=PR-104 (starting at 200 mg/m2) + D on day 1 with prophylactic GCSF. PK was assessed for cycle 1. At U.S. sites, tumor hypoxia was evaluated by positron emission tomography (PET) using F-18-fluoro-misonidazole (FMISO). Results: To date, 23 pts have been dosed: median age 62 yrs (range 30–85); 12 male (52%); median of 2 (range 0–3) prior chemotherapy regimens. Grp A: At 275 mg/m2, 2 DLTs in 3 pts: grade (gd) 4 thrombocytopenia (1pt) and gd 4 thrombocytopenia/gd 4 neutropenic fever (1pt). Non-DLT toxicity included gd 3/4 neutropenia (2 pts). At 140 mg/m2, no DLT in 6 pts. The PR-104 MTD was 140 mg/m2. Grp B: At 400 mg/m2, 2 DLTs (gd 4 neutropenic fever) in 3 pts. At 200 mg/m2, 2 DLTs (gd 3 neutropenic fever) were observed. The PR-104 MTD was <200 mg/m2 with D. Grp C: At 200 (3 pts) and 400 mg/m2 (3 pts), the most frequent adverse events were neutropenia (17%), fatigue (14%), vomiting (14%), headache (12%), nausea (12%), thrombocytopenia (10%) and anemia (8%). Four pts had stable disease: NSC lung (11 cycles), ovarian (7 cycles) breast and melanoma (6 cycles). The maximum plasma concentration of G was 69 ± 38 umol/L; the AUC of D was 3098 ± 2613 ng.h/mL. Tumor hypoxia was detectable in 8/10 pts. Conclusions: The MTD of PR-104 + G is 140 mg/m2. The MTD of PR-104 + D is < 200 mg/m2. Both are less than the single agent MTD of 1100 mg/m2. GCSF allows dose escalation of PR-104 + D (currently accruing at 550 mg/m2). FMISO PET detected tumor hypoxia in a majority of pts. PR-104 does not appear to significantly alter the PK of G or D. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Proacta, Inc. Proacta, Inc. Proacta, Inc.
Reversal of Clinical Resistance to LHRH Analogue in Metastatic Prostate Cancer by the Pineal Hormone Melatonin: Efficacy of LHRH Analogue plus Melatonin in Patients Progressing on LHRH Analogue Alone
Authors: Paola Lissoni, Marina Cazzaniga, Gabriele Tancini, Epifanio Scardino, Roberto Musci, Sandro Barni, Massimo Maffezzini, Tiziano Meroni, Francesco Rocco, Ario Conti, George Maestroni
Journal: European Urology (1997)
Endoscopic Application of Fibrin Glue in the Treatment of Anastomotic Defects, Perforation, and Fistulas in the Gastrointestinal Tract
Authors: H. Groitl, T. Horbach, R. Stangl, J. Scheele
Journal: Endoscopy (1995)

Since December 1984 we have applied fibrin glue endoscopically in the treatment of anastomotic defects, fistulas, and perforation in the upper and lower gastrointestinal tracts in a total of 84 patients. Our patient group consisted of 51 patients with intrathoracic complications after esophageal or stomach surgery and 33 patients with anastomotic defect after colorectal operations or in colorectal or rectovaginal fistulas. Using this approach perianastomotic abscess cavities could be cleansed quickly, and granulation tissue growth and complete healing were promoted in 44 of 51 patients with anastomotic defect in the upper gastrointestinal tract. In the lower gastrointestinal tract the outcome of treatment of anastomotic defects was also good, but not so for fistula treatment. Endoscopic application of fibrin glue is an effective and direct form of biological treatment which puts little strain on the patient.
Increased Levels of Neutrophil-Activating Peptide-2 in Acute Coronary Syndromes
Authors: Camilla Smith, Jan K. Damås, Kari Otterdal, Erik Øie, Wiggo J. Sandberg, Arne Yndestad, Torgun Wæhre, Hanne Scholz, Knut Endresen, Peder S. Olofsson, Bente Halvorsen, Lars Gullestad, Stig S. Frøland, Gøran K. Hansson, Pål Aukrust
Journal: Journal of the American College of Cardiology (2006)
Abstract 1968: Echocardiographic Tissue Deformation Imaging Of The Right Ventricle - A Reliable Technique To Identify Abnormal Regional Function In Arrhythmogenic Right Ventricular Dysplasia/cardiomyopathy
Authors: Arco J Teske, Moniek G Cox, Bart W De Boeck, Niek H Prakken, Pieter A Doevendans, Richard N Hauer, Maarten-Jan M Cramer
Journal: Circulation (2007)

INTRODUCTION: Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) is a cardiomyopathy characterized by fibro-fatty myocardial replacement predominantly in the right ventricle (RV) resulting in RV functional and morphological changes which provide a substrate for arrhythmias and heart failure. Based on visual echocardiographic assessment diagnosis is difficult, and RV dilatation is nonspecific. We hypothesize that new objective and quantitative echocardiographic parameters, such as strain and strain-rate imaging, could reliably identify regional abnormal deformation properties in ARVD/C patients.  METHODS: 17 ARVD/C patients (confirmed by Task Force criteria) and 18 healthy controls were prospectively enrolled. Conventional echocardiography including tissue Doppler imaging (TDI) was performed. Doppler derived velocity, strain and strain-rate were calculated in the RV free wall in the apical, mid and basal segment.  RESULTS: RV dimensions were significantly increased in ARVD/C patients (RVOT 26.4 ± 5.5 vs 40.5 ± 11.5 mm, p  CONCLUSION: TDI derived parameters are superior to conventional echocardiographic parameters in identifying ARVD/C. This novel technique could have additional value in the diagnostic work up of patients suspected of ARVD/C.
Clinical Effectiveness of CRT and ICD Therapy in Heart Failure Patients by Racial/Ethnic Classification
Authors: Boback Ziaeian, Yan Zhang, Nancy M. Albert, Anne B. Curtis, Mihai Gheorghiade, J. Thomas Heywood, Mandeep R. Mehra, Christopher M. O’Connor, Dwight Reynolds, Mary Norine Walsh, Clyde W. Yancy, Gregg C. Fonarow
Journal: Journal of the American College of Cardiology (2014)
The Effect of Pioglitazone on Recurrent Myocardial Infarction in 2,445 Patients With Type 2 Diabetes and Previous Myocardial Infarction
Authors: Erland Erdmann, John A. Dormandy, Bernard Charbonnel, Massimo Massi-Benedetti, Ian K. Moules, Allan M. Skene
Journal: Journal of the American College of Cardiology (2007)
Growing Teratoma Syndrome: Experience of a Single Institution
Authors: P. (a) Maroto, J.M. (a) Tabernero, H. (c) Villavicencio, R. (a) Mesia, E. (a) Marcuello, F.J. (c) Solé-Balcells, C. (a) Sola, J. (b) Mora, F. (c) Algaba, C. (b) Pérez, X. (b) León, J.J. (a) López López
Journal: European Urology (1997)
Abstract 17938: Evidence of Vicious Cycle in Mitral Regurgitation with Prolapse: Secondary Tethering Due to Primary Prolapse Demonstrated by 3-Dimensional Echocardiography Exacerbates Regurgitation
Authors: Kyoko Otani, Masaaki Takeuchi, Kyoko Kaku, Nobuhiko Haruki, Hidetoshi Yoshitani, Robert A Levine, Yutaka Otsuji
Journal: Circulation (2011)

Background: In patients with mitral valve prolapse (MVP), we often observe that non-prolapsed leaflets are tented (apically displaced) (Figure). We hypothesized 1) that secondary left ventricular (LV) dilatation due to primary mitral regurgitation (MR) causes this leaflet tethering and 2) that secondary tethering along with primary prolapse exacerbates malcoaptation and contributes to the severity of MR. Methods: 3DTEE was performed in 20 patients with posterior leaflet (PML) prolapse and intact anterior leaflet (AML) by TEE and surgical observation. 20 patients with cerebral infarction but without cardiac disease served as controls. From mid-systolic 3D zoom datasets, 10 parallel antero-posterior planes of the MV were obtained using i-slice mode (Q-LAB). In each view, area between leaflets and annular line was measured to obtain prolapse and tenting area, respectively. Prolapse/tenting volume of the whole leaflets was obtained as the product of inter-slice distance and the prolapse/tenting area in each plane. LV volume was also measured. MR volume was calculated as LV ejection volume minus aortic stroke volume by pulsed Doppler method. Results: 1) The AML tenting volume was significantly larger in patients with PML prolapse compared to controls (1.04±0.54 vs 0.58±0.14 ml/m2, p&lt;0.001). 2) The AML tenting volume was significantly correlated with mid-systolic LV volume (r=0.61, p&lt;0.001). 3) Sum of prolapse and tenting volume of the whole leaflets strongly correlated with MR volume (r=0.66, p&lt;0.01) (r=0.38 and 0.48 for isolated prolapse and tenting volume, respectively). Conclusion: The results suggest that LV dilatation by primary MVP with MR causes secondary mitral leaflet tethering, which worsens valve leakage and constitutes a vicious cycle.
Sex-Related Differences in Outcomes After Transcatheter or Surgical Aortic Valve Replacement in Patients With Severe Aortic Stenosis
Authors: Mathew Williams, Susheel K Kodali, Rebecca T Hahn, Karin H Humphries, Vuyisile T Nkomo, David J Cohen, Pamela S Douglas, Michael Mack, Thomas C McAndrew, Lars Svensson, Vinod H Thourani, E Murat Tuzcu, Neil J Weissman, Ajay J Kirtane, Martin B Leon
Journal: Journal of the American College of Cardiology (2014)
Abstract 2347: Pulmonary Regurgitation: The Impact on Right Ventricle and the Effect of Percutaneous Pulmonary Valve Replacement
Authors: Lars Søndergaard, Niels G Vejlstrup, Simone Theilade, Jens C Nilsson, Younes Boudjemline, Philipp Bonhoeffer
Journal: Circulation (2007)

Background Despite successful repair of tetralogy of Fallot (TOF), the life expectancy for these patients remains lower than in the general population. This is mainly due to free pulmonary regurgitation (PR). The importance of maintaining a competent valve has been emphasized, but the optimal timing for intervention remains to be established. The purposes of this study were in a pig model to investigate the consequences of the duration of free PR on RV, and the reversibility of these changes after percutaneous pulmonary valve replacement. Methods Thirtysix farm pigs were divided into four groups (A, B, C and D) of nine pigs. At baseline group A, B and C had a percutaneous stent inserted into the pulmonary annulus to create free PR. After 4, 8 and 12 weeks, respectively, group A, B and C underwent percutaneous valve replacement. In order to allow remodelling of RV, the pigs were observed for four weeks after valve insertion before euthanasia. To examine RV function, MRI was performed before stent insertion, before valve replacement, and before euthanasia. Group D served as controls and underwent five MRI examinations: at baseline as well as after four, eight, twelve and sixteen weeks. Results When comparing the group D with group A, B &amp; C, RVEDV and RVESV were found to gradually increase over time. Furthermore, these volumes normalised after valve replacement in group A and B, but remains increased in the group C. Similar, RVEF was normal after valve replacement in group A and B, but impaired in the group the long-term free PR compared to the controls. Conclusion Better timing of valve replacement in patients with free PR after TOF repair is of outermost clinical relevance. This study examined the impact of free PR on RV in a pig model. Despite the relative short duration of the volume overload, the RV underwent irreversible changes. This may be explained by the fact that, in contrast to TOF, the RV is not hypertrophic. The study showed that RV tolerates volume overload from free PR for a certain time, but too late intervention will cause irreversible deterioration of the ventricular function. Thus, the model may serve to identify predictors, e.g. tissue-Doppler measurements or natriuretic peptides, for RV function after valve replacement and thereby optimise timing of intervention.
Abstract 15048: Utility of New Classification Based on Clinical and Lesional Factors after Self-Expandable Nitinol Stenting in Superficial Femoral Artery
Authors: Yusuke Tomoi, Yoshimitsu Soga, Osamu Iida, Keisuke Hirano, Kenji Suzuki, Shinsuke Nanto, Masakiyo Nobuyoshi
Journal: Circulation (2011)

Background: The aim of this study was to investigate the predictive value of clinical classification schemes that assess primary patency after self-expandable nitinol stent (NS) in superficial femo...
Isolated Coronary Artery Bypass Graft Combined With Bone Marrow Mononuclear Cells Delivered Through a Graft Vessel for Patients With Previous Myocardial Infarction and Chronic Heart Failure
Authors: Shengshou Hu, Sheng Liu, Zhe Zheng, Xin Yuan, Lihuan Li, Minjie Lu, Rui Shen, Fujian Duan, Xiaoling Zhang, Jun Li, Xuewen Liu, Yunhu Song, Wei Wang, Shihua Zhao, Zuoxiang He, Hao Zhang, Keming Yang, Wei Feng, Xin Wang
Journal: Journal of the American College of Cardiology (2011)
Abstract 17023: PAI-1 Deficiency Protects Against Accelerated Aging in Klotho-Deficient Mice
Authors: Mesut Eren, Sheila B Murphy, Douglas E Vaughan
Journal: Circulation (2011)

The klotho gene encodes a single-pass transmembrane protein and functions as an aging-suppressor gene, which extends life span when overexpressed and accelerates the development of aging-like phenotypes when disrupted in mice. Klotho protein and FGF receptor function as co-receptors for FGF23 and regulate phosphate and vitamin D metabolism. Klotho also plays a role in the regulation of calcium channel TRPV5, insulin, IGF-1, and Wnt. Klotho deficient (kl -/- ) mice display a phenotype consistent with accelerated aging, including a markedly truncated lifespan (approx. 10 weeks), infertility, osteoporosis, renal sclerosis and obstructive pulmonary disease. The biochemical hallmarks of kl -/- include elevated plasma levels of FGF23, phosphate, calcium, vitamin D, and plasma PAI-1. Given the relationship between elevated PAI-1 and nephrosclerosis and tissue fibrosis, we hypothesized that PAI-1 deficiency would attenuate the phenotype of kl -/- mice. Partial or complete PAI-1 deficiency had no significant effects on serum levels of calcium, phosphate, and creatinine levels, while plasma levels of FGF23 were reduced more than 60-fold in kl -/- -pai-1 -/- (P=0.01) and kl -/- -pai-1 +/- (P=0.004) mice. Furthermore, both kl -/- -pai-1 -/- and kl -/- -pai-1 +/- mice exhibit normal fertility. Most importantly, partial and complete PAI-1 deficiency more than doubled the lifespan of kl -/- mice, with kl -/- -pai-1 -/- living 148±79 days, (n=9, p=0.009)) and kl -/- -pai-1 +/- surviving 208±155 days (n=17, p=0.002). These findings indicate that PAI-1 contributes to some of the critical components of the kl -/- phenotype. These results suggest that drugs that either directly or indirectly reduce PAI-1 might have beneficial effects in delaying age-related pathologies.
A comparison of rapid point-of-care tests for the detection of avian influenza A(H7N9) virus, 2013
Authors: C Baas, I G Barr, R A Fouchier, A Kelso, A C Hurt
Journal: Eurosurveillance (2013)

Six antigen detection-based rapid influenza point-of-care tests were compared for their ability to detect avian influenza A(H7N9) virus. The sensitivity of at least four tests, standardised by viral infectivity (TCID 50 ) or RNA copy number, was lower for the influenza A(H7N9) virus than for seasonal A(H3N2), A(H1N1)pdm09 or other recent avian A(H7) viruses. Comparing detection limits of A(H7N9) virus with Ct values of A(H7N9) clinical specimens suggests the tests would not have detected most clinical specimens.