tbuckley/cabot-search huggingface dataset:
Abstract P192: What is the Role of Chest Compression Depth during Out-of-Hospital CPR?
Authors: Ian G Stiell, Siobhan Everson-Stewart, James Christenson, Sheldon Cheskes, Judy Powell, Blair Bigham, Laurie Morrison, Jonathan Larsen, Graham Nichol, Erik Hess, Christian Vaillancourt, Daniel P Davis, Clifton W Callaway
Journal: Circulation (2008)

Introduction: Current CPR compression depth guidelines were empirically derived. We sought to study patterns of CPR compression depth and their associations with patient outcomes in out-of-hospital cardiac arrest (OOHCA). Methods: We studied OOHCA patients from the Resuscitation Outcomes Consortium Epistry - Cardiac Arrest for whom electronic CPR data were available from proprietary accelerometer technology attached to the prehospital defibrillators. We calculated anterior chest wall depression in millimeters and the period of active CPR (chest compression fraction [CCF]) for each minute of CPR. We controlled for covariates including compression rate and calculated adjusted odds ratios (OR) for any return of circulation (ROSC) and 24 hour survival. We calculated unadjusted OR for hospital discharge. Results: We included 615 adult patients from 6 U.S. and Canadian cities with these characteristics: mean age 68.9; male 62 %; witnessed 43%; bystander CPR 31%; initial rhythms - VF/VT 25%, PEA 17%, asystole 43%, unspecified non-shockable 15%; mean compression rate 103/min; mean compression depth &lt;38mm 51%, 38–51mm 39%, &gt;51mm 11%; median CCF 0.66; outcomes - ROSC 57%, 24 hour survival 18%, discharge 5%. We found an inverse association between depth and compression rate (P&lt;0.0001; see Table ), no association between depth and CCF (P=0.30), and a positive association between CCF and rate (P&lt;0.0001). ORs with 95% CIs for each 5mm increment in compression depth and the outcomes were: 1) ROSC - adjusted OR 1.06 (0.97–1.16), 2) 24 hour survival - adjusted OR 1.01 (0.98–1.03), 3) discharge - unadjusted OR 1.13 (0.95–1.34). Conclusions: We found half of patients received suboptimal compression depth, an inverse association between compression depth and rate, and no clear association between survival and increased compression depth. Further study is required to determine the optimum chest compression depth and its interaction with rate and CCF in order to maximize outcomes. Compression Rate versus Compression Depth
Prognostic factors for patients with Ewing sarcoma (EWS) at first recurrence
Authors: P. Leavey, L. Mascarenhas, N. Marina, Z. Chen, M. Krailo, J. Miser, M. Bernstein, L. Granowetter, H. Grier
Journal: Journal of Clinical Oncology (2007)

10011 Background: The prognosis for patients with recurrent Ewing sarcoma (EWS) is very poor with 5-year survival of 13%. Since 30–40% of patients with newly diagnosed, non-metastatic EWS develop recurrence, the Children's Oncology Group (COG) sought to evaluate prognostic factors for these patients. Data was derived from the phase III, multi-institutional study INT 0091. Methods: Between 1988 and 1994, five hundred and seventy-eight eligible patients with previously untreated EWS or PNET of bone were enrolled on INT 0091. Patients who experienced recurrence or disease progression as their first analytic event were considered. Survival was calculated from date of disease progression to death or last patient contact. Comparisons of the risk for death across groups were accomplished using the log-rank test. Survivor functions were estimated by the method of Kaplan and Meier. Results: Two hundred and sixty-two patients experienced disease progression or recurrence. The median time to first recurrence was 1.3 years (range 0–7.4 years) for all patients, 1.4 years (range 0 to 7.4 years) for patients with initially localized disease and 1 year (range 0 to 6 years) for patients with initially metastatic disease. Time to first recurrence from date of initial diagnosis was a predictor of post-recurrence survival (p&lt;0.0001). Twenty-one percent of patients whose disease recurred or progressed experienced first recurrence 2 or more years from initial diagnosis and had an estimated 5 year post-recurrence survival of 30%. This compares with 7% for those whose first recurrence or progression was earlier. No statistical difference was detected when patients whose disease recurred &lt; 12 months were compared with those whose recurrence was 12–24 months from initial diagnosis. Significant risk factors for death after recurrence included metastatic disease at initial diagnosis, elevated LDH at initial diagnosis and female gender. In patients non-metastatic at initial diagnosis pelvic primary site was also a risk factor for death after recurrence. Conclusions: Patients with longer time to first recurrence represent the subset of patients most likely to survive following recurrence. All patients with recurrent Ewing sarcoma would benefit from collaborative trials to investigate new therapeutic options. No significant financial relationships to disclose.
Abstract 14657: Fiber Intake and Plasminogen Activator Inhibitor-1 in Obese Persons With Type 2 Diabetes, Findings From the Look Ahead (Action for Health in Diabetes) Study
Authors: L. Maria Belalcazar, Dawn C Schwenke, Wei Lang, Steven M Haffner, Julia Rushing, Hiroshi Yatsuya, Russell P Tracy, F. Xavier Pi-Sunyer, Ashok Balasubramanyam, Rebecca S Reeves, Christie M Ballantyne
Journal: Circulation (2010)

Background: Look AHEAD is a multicenter clinical trial designed to examine whether a lifestyle intervention for weight loss will reduce cardiovascular events in overweight/obese persons with type 2 diabetes (T2DM). Dietary fiber is associated with cardiovascular benefits. Its association with markers of fibrinolytic capacity and vascular health in obese persons with diabetes is not well understood. Plasminogen activator inhibitor-1 (PAI-1) is elevated in T2DM and may contribute to cardiovascular disease (CVD) by favoring fibrin deposition and affecting vascular remodeling. Objective: To determine if increased fiber intake in overweight/obese persons with T2DM is associated with lower levels of PAI-1 independently of medication use, adiposity, fitness and alcohol and macronutrient intake. Methods: A subset of 1,679 Look AHEAD participants with dietary data obtained with a food frequency questionnaire had levels of PAI-1 (latent and active) and fitness (exercise stress test) measured at baseline. The associ...
<i>In Utero</i> and Childhood Polybrominated Diphenyl Ether (PBDE) Exposures and Neurodevelopment in the CHAMACOS Study
Authors: Brenda Eskenazi, Jonathan Chevrier, Stephen A. Rauch, Katherine Kogut, Kim G. Harley, Caroline Johnson, Celina Trujillo, Andreas Sjödin, Asa Bradman
Journal: Environmental Health Perspectives (2012)

California children's exposures to polybrominated diphenyl ether flame retardants (PBDEs) are among the highest worldwide. PBDEs are known endocrine disruptors and neurotoxicants in animals.Here we investigate the relation of in utero and child PBDE exposure to neurobehavioral development among participants in CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas), a California birth cohort.We measured PBDEs in maternal prenatal and child serum samples and examined the association of PBDE concentrations with children's attention, motor functioning, and cognition at 5 (n = 310) and 7 years of age (n = 323).Maternal prenatal PBDE concentrations were associated with impaired attention as measured by a continuous performance task at 5 years and maternal report at 5 and 7 years of age, with poorer fine motor coordination-particularly in the nondominant-at both age points, and with decrements in Verbal and Full-Scale IQ at 7 years. PBDE concentrations in children 7 years of age were significantly or marginally associated with concurrent teacher reports of attention problems and decrements in Processing Speed, Perceptual Reasoning, Verbal Comprehension, and Full-Scale IQ. These associations were not altered by adjustment for birth weight, gestational age, or maternal thyroid hormone levels.Both prenatal and childhood PBDE exposures were associated with poorer attention, fine motor coordination, and cognition in the CHAMACOS cohort of school-age children. This study, the largest to date, contributes to growing evidence suggesting that PBDEs have adverse impacts on child neurobehavioral development.
Abstract #670: Anti-angiogenic and antitumor activity of XMT-1107, a fumagillin-derived polymer conjugate, and its in vivo release product XMT-1191
Authors: Laura Akullian, Cheri Stevenson, Tim Lowinger, Robert Fram
Journal: Cancer Research (2009)

XMT-1107, a fumagillin-derived polymer conjugate, and XMT-1191, the in vivo release product of XMT-1107, were evaluated for (1) biochemical activity in a metAP2 inhibition assay, (2) anti-angiogenic activity in a matrigel plug study in mice, and (3) anti-tumor activity in a Caki-1 renal cell carcinoma human tumor xenograft (HTX) model in mice, and their activities were compared with known anti-angiogenic and anti-tumor agents. XMT-1191 displayed potent inhibition against human metAP2 in vitro, in contrast to XMT-1107 which was >50 fold less active. In addition, XMT-1107 caused a decrease in angiogenesis when administered intravenously (iv) to mice in a matrigel plug assay. Lastly, in a Caki-1 HTX study, XMT-1107 exhibited superior activity compared to XMT-1191, as well as compared to known efficacious doses of TNP-470 or sunitinib. Methods: To evaluate the ability of XMT-1107 and XMT-1191 to inhibit human metAP2 enzyme, compounds were incubated with human metAP2 (6 nM) in a buffered medium after which Met-Gly-Pro-AMC was added and release of AMC measured with a Decan Plate reader at 30 sec intervals over 30 min. To evaluate the anti-angiogenic properties of XMT-1107 and XMT-1191, C57BL/6 female mice were implanted with 500 \#956;L matrigel, subcutaneous (sc), containing FGFb and heparin and treated with XMT-1107 or XMT-1191 for 11 days. Plugs were harvested and their microvessel and hemoglobin content quantified. To evaluate the anti-tumor activity of XMT-1107 and XMT-1191, HRLN female mice with sc tumors were treated with XMT-1107, XMT-1191, TNP-470, and sunitinib. Tumor sizes and body weights were monitored for 60 days and tumor growth delays were evaluated. Conclusions: XMT-1107 has enhanced anti-angiogenic and anti-tumor activity compared to its in vivo release product XMT-1191. We hypothesize that conjugation of XMT-1191 to poly(1-hydroxymethylethylene hydroxymethyl formal) (PHF) provides superior tissue distribution and pharmacokinetics resulting in enhanced biologic activity compared to administration of XMT-1191 alone. Additionally, the activity of XMT-1191 against human metAP2 in vitro was significantly greater than the activity of XMT-1107, which does not release significant amounts of XMT-1191 under the assay conditions. The enhanced anti-angiogenic, and in vivo anti-tumor activity of XMT-1107 compared to XMT-1191 demonstrates the utility of conjugating XMT-1191 to PHF. In addition, XMT-1107 has enhanced anti-cancer activity compared to known anti-angiogenic agents TNP-470 and clinically effective sunitinib in a Caki-1 HTX model. In conclusion, the anti-tumor and anti-angiogenic properties of XMT-1107 and the biochemical activity of XMT-1191 support the potential clinical utility of XMT-1107 as an anti-cancer agent.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 670.
Abstract 9403: A Periodontal Pathogen Accelerates the Progression of Abdominal Aortic Aneurysm via Toll-Like Receptor-2 Signaling
Authors: Norio Aoyama, Jun-Ichi Suzuki, Masahito Ogawa, Ryo Watanabe, Yuichi Izumi, Yasunobu Hirata, Ryozo Nagai, Mitsuaki Isobe
Journal: Circulation (2011)

Introduction-- Abdominal aortic aneurysm (AAA) is a life-threatening disorder. Periodontopathic bacteria have been detected at a high rate in specimens obtained from the aortic walls of AAA patients. It has been shown in an animal study that periodontopathic bacteria induce the progression of AAA. Toll-like receptors (TLRs) are key receptors of virulence factors of many periodontal bacteria. Hypothesis-- We assessed the hypothesis that TLR plays a fundamental role in periodontopathic bacteria-accelerated AAA progression. Methods-- AAA was experimentally produced with wild-type mice, TLR-2 deficient mice and TLR-4 deficient mice by the peri-aortic application of 0.25 mol/L CaCl2, while NaCl was used as a control. The mice were injected once per week with live Porphyromonas gingivalis (P.g.), which is a major periodontal pathogen, or vehicle. Four weeks after the application of either CaCl2 or NaCl, the aortic samples were obtained. Histological and immunohistochemical analyses were performed to assess the mechanism of AAA progression. Results-- P.g.-injected and CaCl2-treated wild-type mice (n = 10) showed a larger increase (1.71 +/− 0.05-fold vs. before operation) than uninfected CaCl2-treated wild-type mice (n = 10) (1.51 +/− 0.09-fold vs. before). Although the aortic diameter of P.g.-injected and CaCl2-treated TLR-4 deficient mice (n = 11) showed a significant increase (1.28 +/− 0.20-fold vs. before, p &lt; 0.05), the aortic diameter of P.g.-injected and CaCl2-treated TLR-2 deficient mice (n = 10) did not increase after the operation (1.07 +/− 0.19-fold vs. before). TLR-2 deficient mice which were injected with P.g. and treated with CaCl2 showed less elastic degradation than wild-type or TLR-4 deficient mice with histological analysis. Immunohistochemical analysis showed that the level of matrix metalloproteinase-2 in the aortic wall of the TLR-2 deficient mice was dramatically lower (1.0 +/− 0.4) than in the wild-type mice (3.0 +/− 0.6, p &lt; 0.05). Conclusion-- In conclusion, infection with P.g. could accelerate the progression of experimental AAA with TLR-2 signaling.
Abstract 12692: MicroRNA-Regulated p53 Expression in Cardiac Hypertrophy That Transits to Heart Failure
Authors: Biswajit Das, Nikolai Sopko, Subha Sen
Journal: Circulation (2010)

The molecular mechanisms triggering heart failure (HF), the major cause of mortality/morbidity worldwide, are not fully known. Small conserved noncoding RNAs of ∼22 nucleotides, called microRNAs (miRNAs), reportedly are involved in cardiac diseases. But what the altered miRNAs do as cardiac hypertrophy (CH) worsens to HF is unknown. We aim to identify and define the role of the altered miRNAs that participate during progression of CH to HF. We identified a unique miRNA involved in HF by various means: transgenic mice overexpressing cardiac myotrophin (myo-Tg mice, developed in our laboratory), which develop CH that progresses to HF, mimicking all symptoms of human HF; transverse aortic constriction (TAC) mice; and tissue samples from excised human hearts with end-stage HF. Using a array platform containing >13,000 probes, global miRNA expression profiling of failing hearts of myo-Tg mice revealed significant (p 2.0 vs. wild-type con...
Guidelines on circumcision
Authors: John D Dalton
Journal: BMJ (1997)

<h3>Abstract</h3> The growth hormone and insulin-like growth factor (IGF) system is integral to human growth. Genome-wide association studies (GWAS) have identified variants associated with height and located near the genes in this pathway. However, mechanisms underlying these genetic associations are not understood. To investigate the regulation of the genes in this pathway and mechanisms by which regulation could affect growth, we performed GWAS of measured serum protein levels of IGF-I, IGFBP-3, PAPP-A2, IGF-II, and IGFBP-5 in 839 children (3-18 years) from the Cincinnati Genomic Control Cohort. We identified variants associated with protein levels near <i>IGFBP3</i> and <i>IGFBP5</i> genes, which contain multiple signals of association with height and other skeletal growth phenotypes. Surprisingly, variants that associate with protein levels at these two loci do not colocalize with height associations, confirmed through conditional analysis. Rather, the <i>IGFBP3</i> signal (associated with total IGFBP-3 and IGF-II levels) colocalizes with an association with sitting height ratio (SHR); the <i>IGFBP5</i> signal (associated with IGFBP-5 levels) colocalizes with birth weight. Indeed, height-associated SNPs near genes encoding other proteins in this pathway are not associated with serum levels, possibly excluding PAPP-A2. Mendelian randomization supports a stronger relationship of measured serum levels with SHR (for IGFBP-3) and birth weight (for IGFBP-5) than with height. In conclusion, we begin to characterize the genetic regulation of serum levels of IGF-related proteins in childhood. Furthermore, our data strongly suggest the existence of growth-regulating mechanisms acting through IGF-related genes in ways that are not reflected in measured serum levels of the corresponding proteins.
Abstract 4876: LAMP2 Cardiomyopathy is a Particularly Adverse Phenocopy of Sarcomeric Hypertrophic Cardiomyopathy
Authors: Barry Maron, William C Roberts, Michael Arad, Carolyn Y Ho, Tammy S Haas, Paolo Spirito, Gregory B Wright, Adrian K Almquist, Gina Baffa, Jonathan G Seidman, Christine C Seidman
Journal: Circulation (2008)

Mutations in the X-linked lysosome-associated membrane protein gene (LAMP2; Danon disease) produce a morphologic phenocopy of sarcomeric hypertrophic cardiomyopathy (HCM) in young patients, characterized by extreme left ventricular (LV) hypertrophy and pre-excitation. However, the natural history of this newly recognized cardiomyopathy is incompletely resolved. Seven young asymptomatic patients with LAMP2 cardiomyopathy were identified at ages 8 to 15 years; 6 were male. LV hypertrophy was particularly marked (septal thickness 25– 65 mm; mean 42±17) in the presence of nondilated LV cavity. On each ECG, Wolff-Parkinson-White pre-excitation pattern was associated with markedly increased voltages (74±38mm for R- or S-wave). Over the 7±3 year follow-up from initial cardiac diagnosis, all 7 patients experienced particularly adverse disease consequences associated with progressive LV wall thinning and cavity dilatation and systolic dysfunction (ejection fraction, 29±7%) by the ages of 12 – 24 years (mean 20). Of the 7 patients, 5 either died of progressive heart failure, had heart transplantation or were considered for a donor heart; 2 others had sudden death events, including one fatal ventricular tachyarrhythmia refractory to defibrillator therapy and one appropriate defibrillator shock in an asymptomatic female survivor. Pathologic examination of hearts at autopsy showed histopathologic findings compatible with both HCM due to sarcomere protein mutations (i.e., extensive myocyte disarray, intramural small vessel disease, myocardial replacement scarring), and also evidence of a storage disease process (i.e., clusters of myocytes with vacuolated sarcoplasm within fibrotic areas). Heart weights, 1266 and 1425 grams, are the most substantial recorded for hypertrophic cardiomyopathies. LAMP2 cardiomyopathy is a uniformly profound, and particularly deleterious disease entity, causing refractory heart failure with systolic dysfunction as well as sudden death in young patients &lt; 25 years of age. This novel phenocopy of sarcomeric HCM underscores the power of molecular diagnosis for predicting prognosis, and should also raise consideration for intervention with early heart transplantation.
Abstract 18241: Enhancement of Capillary Perfusion through Increased Arteriolar Pressure with Drag Reducing Polymers
Authors: John Pacella, Marina Kameneva, Linda Lavery, Judith Brands, Flordeliza Villaneuva
Journal: Circulation (2010)

Background: Drag reducing polymers (DRPs) restore capillary perfusion during severe coronary stenosis in canines. It is posited that DRPs alter blood flow hydrodynamics such that there is a reduction in pressure loss in the arterial compartment, thus providing higher precapillary driving pressure and enhanced capillary perfusion. However, this has not been proven. We tested the hypothesis that DRPs enhance capillary perfusion by reducing upstream arteriolar pressure loss. We employed intravital microscopy and the servonull technique for direct intra-arteriolar pressure measurement before and after DRP infusion in rats. Methods: Rats (n=15) were sedated and the cremaster muscle was mounted on a microscope stage. A catheter was placed in the internal jugular vein for DRP infusion. An arteriole (range 48 to 132 μm diameter) was identified and cannulated using a 3 degree of freedom micromanipulator and 3 μm tipped glass micropipette. Arteriolar pressure measurements were obtained at baseline and repeated 20 m...
Abstract 16068: Evaluation of Current-Based Impedance Compensation Defibrillation in Pre-Hospital Sudden Cardiac Arrest with Different Transthoracic Impedances
Authors: Yongqin Li, Weilun Quan, Gary Freeman, Wanchun Tang
Journal: Circulation (2010)

Introduction: Modern external defibrillators use impedance compensation techniques because the transthoracic impedance (TTI) is a major factor which influences the intracardiac current flow during ...
Preventive administration of UDCA after liver transplantation for primary biliary cirrhosis is associated with a lower risk of disease recurrence
Authors: Alexie Bosch, Jérôme Dumortier, Delphine Maucort-Boulch, Jean-Yves Scoazec, Dominique Wendum, Filomena Conti, Isabelle Morard, Laura Rubbia-Brandt, Benoit Terris, Sylvie Radenne, Ludovico Abenavoli, Raoul Poupon, Olivier Chazouillères, Yvon Calmus, Olivier Boillot, Emiliano Giostra, Christophe Corpechot
Journal: Journal of Hepatology (2015)
CSF somatostatin in obsessive-compulsive disorder
Authors: M Altemus, T Pigott, F L'Heureux, C L Davis, D R Rubinow, D L Murphy, P W Gold
Journal: American Journal of Psychiatry (1993)

Because the central administration of somatostatin to experimental animals produces behaviors with some similarities to the compulsions of patients with obsessive-compulsive disorder and because serotonin reuptake inhibitors have been reported to reduce brain content of somatostatin, the authors examined central somatostatin activity in patients with obsessive-compulsive disorder.CSF for measurement of somatostatin was obtained from 15 drug-free outpatients with obsessive-compulsive disorder and 27 normal volunteers.The mean CSF somatostatin level was significantly higher in the patients with obsessive-compulsive disorder than in the normal subjects.Although the functional significance of this finding is unknown, these data are consistent with a role for somatostatin in the clinical symptomatology of obsessive-compulsive disorder and its response to neuropharmacological agents. The high levels of CSF somatostatin reported here in a patient subgroup whose predominant symptoms consisted of overly focused, perseverative thought processes are in contrast to the consistently low levels of CSF somatostatin seen in patients with a spectrum of disorders characterized by substantial cognitive deficits.