tbuckley/cabot-search huggingface dataset:
Adenine Phosphoribosyltransferase Deficiency Presenting with Supposed ‘Uric Acid’ Stones: Pitfalls of Diagnosis<sup>1</sup>
Authors: H A Simmonds, A Sahota, C F Potter, J S Cameron, G A Rose, D I Williams, T M Barratt, D G Arkell, K J Van Acker
Journal: Journal of the Royal Society of Medicine (1978)
Noise trauma after inflation of air bags in low speed car crashes
Authors: S S M Hussain, G. Buckley
Journal: BMJ (1999)

Proportions of cases (babies with neonatal encephalopathy) and controls having complicated* and uncomplicated † deliveries in Badawi et al's study No (%) of cases (n=164) No (%) of controls (n=400) Unadjusted odds ratio (95% CI) Complicated delivery 79 (48) 101 (25) 2.75 (1.88 to 4.02) Uncomplicated delivery 85 (52) 299 (75) 0.36 (0.25 to 0.53) *Complicated deliveries: instrumental deliveries
Abstract 16890: Ablation of Atrial Fibrillation Rotors and Focal Sources Improves Outcome Over Conventional Ablation Alone in Independent Laboratories: Multicenter Validation of Focal Impulse and Rotor Modulation (FIRM)
Authors: John M Miller, David E Krummen, Paul Clopton, John D Day, James P Daubert, Kenneth A Ellenbogen, John D Hummel, Robert C Kowal, Moussa C Mansour, Vivek Y Reddy, Kalyanam Shivkumar, Jonathan S Steinberg, Vijay Swarup, Kevin R Wheelan, Sanjiv M Narayan
Journal: Circulation (2013)
Abstract 926: Gating Properties of SCN5A Mutants Predict Response to Mexiletine in LQT3 Patients
Authors: Yanfei Ruan, Nian Liu, Mirella Memmi, Barbara Colombi, Raffaella Bloise, Rimini Alessandro, Carlo Napolitano, Silvia G Priori
Journal: Circulation (2006)

Background: Although mexiletine (Mex) has been proposed as a gene specific therapy in LQT3 patients, the QT shortening effect varies among patients harboring different mutations. Since Mex block of...
Immunobiology of Visualizable Brain Tumor Cells: Gamma Interferon Induces Changes in the Immune Environment in Each Compartment of Brain Tumor Spread
Authors: Lois A. Lampson, Michael P. Sethna
Journal: Neuro-Oncology (1991)

We have developed a rat model system that allows study of the cellular immune response to individual, visualizable brain tumor cells. The identifiable tumor cells grow and spread in ways that mimic the spread of human brain tumors. A single focal injection of a moderate dose of gamma interferon (IFN-g) was shown to change the immune environment in each anatomic compartment where tumor spread is seen: IFN-g increases entry of inflammatory cells across brain blood vessels. In addition, IFN-g increases expression of major histocompatibility complex (MHC) antigens by cells of the blood vessel walls, in the ependymal lining of the ventricles, and within the parenchyma proper. These effects of IFN-g were defined in tumor-free rats. Studies in progress are defining the effects of IFN-g on tumor growth in each anatomic compartment.
Abstract 5257: Priming with Angiopoietin-1 Augments Angiogenic Potential of Peripheral Blood Stem Cells Mobilized with Granulocyte-Colony Stimulating Factor
Authors: Choon Soo Lee, Min-Seok Kim, Hyun-Jai Cho, Jin Hur, Yoo-Wook Kwon, Su-Yeon Choi, Hyun-Jae Kang, Sang-Hyun Kim, Byung-Hee Oh, Young-Bae Park, Hyo-Soo Kim
Journal: Circulation (2008)

Background: We introduce the concept of ‘priming’ mobilized peripheral blood stem cells( mob -PBSCs) with G-CSF using Angiopoietin-1(Ang-1). Methods and Results: Ang-1 was administered as a priming agent because it was found that mob PBSCs highly express Tie2, Ang-1 receptor [19.2±3% vs. 1.2±0.2%, p&lt;0.01 for mob PBSCs vs PBMCs]. We investigated whether the effect of Ang-1 on mob PBSCs differentiation is mediated via the transcriptional regulation of ets-1. The gene expression of ets-1 increased in a time dependent manner after Ang-1 stimulation(400ng/ml) in mob PBSCs. Compared with vehicle, treatment with Ang-1 for 4 hours resulted in stronger expression of endothelial markers, such as, CD31 and VE-cadherin, which were significantly reduced with antisense ets-1 oligodeoxynucleotides(ODN). These results were also confirmed at the protein level by FACS analysis. We postulated that integrins that contain an ets-1 binding motif in their promoter region may be activated by Ang-1, such as α4β1 and α5β1 integrins. RT-PCR showed increased mRNA expression of α4, α5, and β1 integrins after Ang-1 stimulation, and its attenuation after transfection with antisense ets-1 ODN. These results were also confirmed at the protein level by FACS analysis. To correlate these findings with functional changes in mob PBSCs, we performed in vitro adhesion assays. Ang-1 stimulation increased mob PBSCs adhesion to HUVECs and fibronectin, while pretreatment with anti-hTie2 or anti-integrin antibody prior to Ang-1 stimulation abrogated these results. And, we checked the effect of Ang-1 in vivo model. mob PBSCs were obtained from rabbit and primed with COMP-Ang1(400ng/ml) for 4 hours. mob PBSCs were labeled with Tc-99m HMPAO and were injected into a central artery of rabbit ear. mob PBSC engraftment was quantified by the ratio of whole rabbit ear radioactivity over total infused mob PBSC radioactivity. In contrast, cells primed with COMP-Ang1 showed markedly increased engraftment by 53±33%( p &lt;0.05). Finally, mob PBSCs primed with Ang-1 enhanced neovascularization in a nude mouse hindlimb ischemia model. Conclusion: These results suggest that mob PBSCs priming with Ang-1 may enhance the efficacy of transplanted mob PBSCs in terms of increasing neovascularization in ischemic tissue.
A Phase 2a, Open-Label, Dose-Finding Study To Determine The Safety and Tolerability Of Sotatercept (ACE-011) In Adults With Beta (β)-Thalassemia: Interim Results
Authors: Maria-Domenica Cappellini, John Porter, Raffaella Origa, Gian Luca Forni, Adberrahmane Laadem, Frédéric Galacteros, Dimana Miteva, Victoria Sung, Rajesh Chopra, Jean-Benoît Arlet, Jean-Antoine Ribeil, Kenneth Klesczewski, Kenneth Attie, Maciej Garbowski, Olivier Hermine
Journal: Blood (2013)
Abstract 4875: Obstructive Sleep Apnea is Associated With Increased Aortic Stiffening, Microalbuminuria and Endothelial Dysfunction in Hypertensives: A Double Enemy to the Vasculature
Authors: Costas Thomopoulos, Costas Tsioufis, Alexandros Kasiakogias, Eirini Andrikou, Ioannis Andrikou, Anastasia Mazaraki, Manos Alchanatis, Thomas Makris, Christodoulos Stefanadis
Journal: Circulation (2009)

Introduction: Incriminating evidence of an adverse effect of obstructive sleep apnea (OSA) on the vasculature is increasing. We investigated the degree of vascular impairment in the high risk population of hypertensives with OSA by diverse atherosclerotic surrogates. Methods : We studied 62 consecutive patients [49 men, aged 48±7 years, 31 smokers, body mass index (BMI) 32±4kg/m 2 ) with untreated hypertension and OSA diagnosed by polysomnography (PSG) [apnea/hypopnea index (AHI)≥5], and a control group of 70 untreated hypertensives without OSA (AHI&lt;5) matched for age, sex, body mass index, smoking status and 24h systolic blood pressure (BP). All subjects underwent 24h ambulatory BP monitoring, echocardiography and aortic stiffness evaluation by means of carotid - femoral pulse wave velocity (PWV) using an automatic device (Complior SP). Metabolic profile, serum creatinine levels (sCr), glomerular filtration rate (eGFR), and asymmetric dimethyl-arginine (ADMA) were assessed from a morning blood sample. The albumin/creatinine excretion ratio (ACR) was calculated from two non consecutive urine morning samples. Results : Hypertensives with OSA had similar 24h systolic BP (140±9 vs. 138±6 mmHg, p=NS) but higher 24h diastolic BP levels (87±6 vs. 84±7 mmHg, p=0.03) compared to the control group. Left ventricle mass index was greater in the OSA group (109±23 vs. 100±25 gr/m 2 , p=0.04), while relative wall thickness (0.43±0.07 vs. 0.43±0.08) and metabolic profile did not differ (p=NS for all). Although sCr and eGFR were similar between the two groups (0.96±0.18 vs. 0.94±0.18mg/dl and 114±30 vs. 116±27 ml/min/1.73m 2 , p=NS for both), patients with OSA exhibited higher levels of logACR and logADMA compared to those without (1.07±0.31 vs. 0.66±0.38 mg/g, −0.25±0.1 vs. −0.31±0.1 μ mol/l, respectively, p&lt;0.0001 for both) even after adjustment for confounders. Furthermore, PWV was elevated in OSA patients compared to the control group. (8.2±0.7vs.7.2±0.9m/sec, p&lt;0.001). In the entire study population logAHI was correlated with PWV (r=0.35, p&lt;0.001), logADMA (r=0.30, p=0.001) and logACR (r=0.34, p&lt;0.0001). Conclusions : Elevated values of ADMA, PWV and ACR in hypertensives with OSA reveal an atherosclerotic state enhanced by sleep disordered breathing.
Abstract 3937: Generation and Analysis of Neural Crest- and Endothelial-specific Mutant Mice for Foxc1
Authors: Seungwoon Seo, Hisaki Hayashi, Tsutomu Kume
Journal: Circulation (2008)

The forkhead transcription factor Foxc1 has been implicated in craniofacial, ocular and cardiovascular development. Foxc1 is expressed in mesoderm- and neural crest (NC)-derived cells, including endothelial cells (ECs) of the heart and blood vessels and vascular smooth muscle cells. However, the precise role of Foxc1 in specific cell types still remains unclear. Therefore, to define the distinct function of Foxc1 in NC and EC, we have generated conditional mutant mice for Foxc1 crossed with either Tie2-Cre or Wnt1-Cre mice. EC-specific Foxc1 mutants survive until adulthood with no apparent embryonic defects, although they show vascular abnormalities in the adult. By contrast, NC-specific Foxc1 mutants die perinately with haemorrhagic hydrocephalus, rudimentary frontal bones, and abnormal patterning of the aortic arch. NC-derived cells also give rise to the stroma and endothelium of the cornea, an avascular organ whose transparency is critical for vision. Importantly, we found that NC-specific Foxc1 mutants show failure of the formation of the anterior chamber and corneal endothelium in the eye. Mutant corneal stroma is much thicker than normal with increased cell proliferation. Most Intriguingly, NC-specific Foxc1 mutants exhibit ectopic neovascularization in the cornea with significant upregulation of Mmp9, sFlt1, Flt1 and Tek at E15.5, while Vegfa and Fgf expression is not changed. By contrast, the cornea of EC-specific Foxc1 mutants is normally formed and avascular. These data suggest that the cell-autonomous function of Foxc1 in the neural crest is essential for craniofacial and cardiovascular development and that Foxc1 plays an important role in inhibition of vascular formation in the cornea.
Abstract 2238: New Pharmacokinetic Models for Quantitative Molecular Imaging of Plaque Angiogenesis with Intergrin-targeted Nanoparticles
Authors: Hoon Sim, Anne Neubauer, Shelton Caruthers, Gregory Lanza, Samuel Wickline, David Sept
Journal: Circulation (2008)

Cardiovascular molecular imaging with targeted nanoparticles has emerged as a promising method for early detection of atherosclerosis and vulnerable plaque. However, traditional pharmacokinetic models for diffusible drugs are inadequate to describe the efficacy of nanoparticle carriers of diagnostic and therapeutic cargos. To quantify blood and MRI tissue signals from gadolinium-loaded nanoparticles (Gd-NP) targeted to avb3 integrins expressed on angiogenic capillaries in the aortas of cholesterol-fed rabbit, a novel 4 compartment open PK model was developed that utilized a unique simultaneous fitting scheme. In 10 rabbits fed 0.25% cholesterol for 3 months, the concentration of nanoparticles was measured serially from blood samples after injection of 1 ml/kg of targeted or nontargeted Gd-NP. The MRI proton signatures emanating from nanoparticles bound to the expanded vasa vasorum of the descending thoracic aorta was computed for all aortic cross sections in 1.5T T1w fa-suppressed spin-echo images. Based on the PK analysis, the concentration of targeted nanoparticles in the aortic wall is double that of non-targeted nanoparticles. Notably, this signal enhancement is achieved with 20x less gadolinium (4.6x10 −3 mmol Gd/kg BW) as compared with the dose of conventional gadolinium agents (0.1 mmol/kg). Further, the PK analysis shows that the targeted nanoparticles are more than three times more effective at reaching the aortic wall. These results should facilitate development and use of nanotechnologies intended for early detection of atherosclerosis and provide enhanced understanding of the kinetics and mechanisms of active targeting of plaque angiogenesis.
A pilot study of the immunohistochemical pattern of neuropilin-2 (NRP2) labeling and correlation with tumor stage in colon cancer.
Authors: Hongliu Sun, Ashleigh M. Kussman, Carol Freeman, Judy Meredith, Kenneth Hensley, Cara Gato-Weis, Roland T. Skeel, Ali Nawras, Luis De Las Casas
Journal: Journal of Clinical Oncology (2012)

e14098 Background: Neuropilin 2 (NRP2) is a transmembrane glycoprotein, non-associated with kinase domains, implicated in neovascularization and metastasis of colon cancer. NRP2 has been proposed as a molecular marker for targeted cancer therapy based on its multiple functions in cancer promotion. NRP2 signaling pathway and its expression have been demonstrated in many carcinomas. To the best of our knowledge, no description of the immunohistochemical staining pattern of NRP2 in colon cancer has been published in the English medical literature. The aim of this study is to investigate the NRP2 labelilng pattern in colon cancer and correlate it with tumor stage. Methods: Tumor sections from 35 randomly selected colectomy specimens with colorectal cancer collected during the last three years were retrieved from the University of Toledo Medical Center Department of Pathology archival material. Formalin fixed, paraffin embedded, 4 μm tissue sections containing invasive tumor were immunolabeled with a commercial antibody against NRP2, using a Ventana Benchmark LT automated instrument. Randomized, immunolabeled colon cancer tissue sections were blindly reviewed by two pathologists. Cytoplasmic and nuclear expression of NRP2 by tumor cells was graded as negative (no staining), focal (staining in &lt;50% of cells), and diffuse (staining in ≥ 50% of cells). Adjacent benign colonic mucosa was used as an internal control. Results: No T1 or T2 tumor displayed diffuse nuclear labeling for the NRP2 epitope. In contrast, 13/20 T3 tumors (65%) and 4/4 T4 tumors (100%) displayed diffuse nuclear labeling. The association of diffuse nuclear NRP2 labeling with tumor grade was highly statistically significant (p=0.0055 by Chi-squared test). In contrast to nuclear labeling, cytoplasmic staining was observed in all stages and varied from negative to diffuse, but demonstrated no significant correlation with stage. Conclusions: This pilot study on colon cancer specimens suggests that diffuse nuclear immunolabeling of neuropilin-2 is indicative of a higher tumor stage. This finding suggests a potential use for this marker as a prognostic indicator for colon cancer in small biopsy samples.
Abstract P134: Lifestyle Modifications are Associated with Decreased Coronary and Carotid Atherosclerotic Burden - A Systematic Review
Authors: Sunny Jhamnani, Layla Heimlich, Fred King, Dhavalkumar Patel, Brian Walitt, Joseph Lindsay
Journal: Circulation (2013)

Introduction: Lifestyle modifications are the crux of atherosclerotic disease management. Studies evaluating the evidence behind this have been limited by their small population sizes or mixed resu...
Abstract 6234: Cost-Effectiveness Analysis Demonstrates Superiority of Screening Young Athletes with 12-Lead Electrocardiogram versus History and Physical in Preventing Sudden Cardiac Death
Authors: Matthew T Wheeler, Paul A Heidenreich, Victor F Froelicher, Mark A Hlatky, Euan A Ashley
Journal: Circulation (2008)

Sudden cardiac death (SCD) is a rare but frightening event among young athletes. The Italian experience demonstrates a reduction in athlete SCD by screening with history, physical, and 12-lead electrocardiogram (ECG). American guideline statements have not recommended ECG for screening athletes due to perceptions of high cost and unclear effectiveness. We sought to model the cost-effectiveness (CE) of history and physical (H&amp;P), ECG plus H&amp;P, and no screening in US high school and college competitive athletes. A decision analysis model was used. Risks, prevalence, and test characteristics were derived from the medical literature. Costs were derived from publicly available datasets. Markov processes were used to simulate the natural histories of screened athletes. One-way sensitivity analyses and Monte Carlo simulation of all variables in the estimated ranges were performed. A societal perspective was used. Screening with an ECG plus H&amp;P has lower overall costs and better outcomes than use of H&amp;P alone. Compared with no screening, H&amp;P saves 0.57 life years (LY) per 1000 athletes screened at an incremental cost of $111 per athlete, yielding a CE ratio of $195,600 per LY saved (simulation based 95% CI $116,000–514,000). ECG plus H&amp;P when compared to no screening saves 2.7 LY per 1000 athletes at an incremental cost of $199 per athlete, for a CE ratio of $74,100 per LY saved (95% CI $46,000–158,000). Probabilistic sensitivity analysis shows that ECG plus H&amp;P is the preferred strategy over H&amp;P in terms of cost-effectiveness in 99.5% of simulations. ECG plus H&amp;P is cost-effective below a threshold value of $100,000 per LY saved in 89% of simulations, while H&amp;P is cost-effective in 1% of simulations. If the reduction in SCD risk per screening-identified, at-risk athlete is below 33%, or if more than 12% of screens are false positive, screening with ECG plus H&amp;P is no longer cost effective. ECG plus H&amp;P is superior to H&amp;P for screening young athletes in our cost-effectiveness model. The incremental cost of adding an ECG, including screening, secondary testing, and subsequent treatment is under $100 per athlete screened. These data should inform the ongoing debate concerning pre-participation screening of US student-athletes.
Abstract 2277: Verapamil Prevents Fatal Arrhythmia by Blocking Cardiac Ryanodine Receptor in a Mouse Model of Catecholaminergic Polymorphic Ventricular Tachycardia Carrying Calsequestrin-2 Mutation
Authors: Hiroko Wakimoto, Ronny Alcalai, Libin Wang, Michael Arad, Tetsuo Konno, Jonathan G Seidman, Christine E Seidman, Charles I Berul
Journal: Circulation (2009)

Catecholaminergic polymorphic ventricular tachycardia (CPVT), a familial arrhythmia syndrome caused by ryanodine receptor (RyR2) or calsequestrin-2 (CASQ2) gene mutations, is characterized by stres...
Abstract 9345: Effects of Telmisartan on Inflammatory Cytokines and Coronary Plaque Component Assessed by Integrated Backscatter Intravascular Ultrasound in Hypertensive Patients
Authors: Koji Yamaguchi, Tetsuzo Wakatsuki, Takeshi Soeki, Toshiyuki Niki, Yoshio Taketani, Hiroyasu Oezuka, Sachiko Bando, Noriko Tomita, Kenya Kusunose, Takashi Iwase, Hirotsugu Yamada, Masataka Sata
Journal: Circulation (2011)

Backgrounds: Recently, assessment of the plaque composition has become possible using an integrated backscatter intravascular ultrasound (IB-IVUS). The pleiotropic effect of telmisartan has been focused, however, effects of telmisartan on coronary plaque component and inflammatory cytokines are not known. Methods: A total of 31 patients with hypertension were randomized to two groups: telmisartan group (treatment with telmisartan [80mg/day, n=16]) or control group (other antihypertensive drugs except renin-angiotensin system blocker, n=15) for six months. The tissue characteristics of target coronary plaque in each patient were analyzed using IB-IVUS before and after treatment. We also measured plasma levels of inflammatory cytokines sampled in coronary sinus (CS) and peripheral vein (PV). Results: Mean lumen area significantly increased (7.9±2.2 to 8.5±2.6 mm2, p&lt;0.05) and plaque volume significantly decreased (21.1±6.0 to 19.4±6.2 mm3, p&lt;0.01) after treatment with telmisartan. Additionally, significant increases of fibrous volume (47.3±9.3 to 63.1±4.1%, p&lt;0.05) and reduction of lipid volume (37.5±15.4 to 24.8±8.6%, p&lt;0.05) were observed on IB image analyses in the telmisartan group, while there were no significant changes in plaque component in the control group. The CS-levels of MMP3 and hsCRP were smaller after than before treatment with telmisartan (7.6±6.1 to 5.5±4.9 ng/ml, 5.6±6.0 to 2.2±2.4 mg/l, p&lt;0.05, respectively), however, there were no significant differences in cytokine levels between pre- and post-treatment with other antihypertensive drugs. In the PV-levels of those cytokines, there were no significant differences between pre- and post-treatment in the two groups. Conclusions: Decreased local inflammatory response and plaque stabilization on IB image analyses were observed after six months of telmisartan treatment. These findings might be associated with local anti-inflammatory and antiarteriosclerotic effects of telmisartan.
Psychiatric disorders and homicide recidivism
Authors: J Tiihonen, P Hakola
Journal: American Journal of Psychiatry (1994)

There are no firm epidemiologic data concerning psychiatric disorders associated with homicide recidivism. The authors studied all homicide recidivists who were incarcerated in Finnish prisons or high-security hospitals and had committed their last offense during the 3-year period July 1, 1988-June 30, 1991. All recidivists (13 subjects) could be considered to suffer from either severe alcoholism combined with personality disorder (N = 11, 85%) or from schizophrenia (N = 2, 15%).
High-throughput technologies to personalize medical treatment in patients with metastatic breast cancer.
Authors: R. Wolp-Diniz, J. De La Cruz, V. Scott, C. Richon, M. Campone, T. D. Bachelot, F. Dalenc, V. Lazar, J. Soria, F. Andre
Journal: Journal of Clinical Oncology (2010)

1047 Background: To apply high throughput technologies (CGH array, Hot Spot Mutations arrays) in daily practice in order to drive patients to tailored targeted therapies. Methods: High resolution CGH-arrays (Agilent 4*44K) and Hot Spot mutations arrays (including mutations in PI3KCA / ATK / PTEN) were done in the context of daily practice in patients with pretreated metastatic breast cancer. Quality control was assessed by evaluating the percent of invalid probes on CGH array (success:<2% invalid probes). A gene was considered as amplified in case of log2ratio>1. The goal was to drive patients into phase I/II trials according to their molecular profiles. Results: 135 patients were included in the study. 108 out of 135 samples (80%) successfully passed the quality control. Success rate was higher in frozen samples (92% success) as compared to paraffin-embedded samples (32% success). ERBB2 status by CGH array well correlated with HER2 overexpression assessed by IHC (106/108 samples, including one ERBB2 amplification not detected by IHC). Results were generated within one month in all patients. A targetable molecular event was identified by CGH arrays in 39 patients. This includes FGFR1 amplification (n=12), FGF4/PAK1 amplification (n=6) and rare other events (n=21). Rare events included IGF1R, IGF1, FGFR2, FGFR4, JAK2, AKT3 amplifications (n<3). Hot Spot Mutations arrays identified a PI3KCA mutation in 11 patients, and AKT mutation in 7 patients. Between June 2009 and January 2010, 15 patients were driven to specific phase I/II clinical trials according to the identified target. Results: Conclusions: This study shows that high throughput technologies are feasible in the context of daily practice and allow to drive a significant number of patients to dedicated phase I/II trials. This study emphasizes the high incidence of patients (19%) presenting a rare, but potentially relevant, molecular event. For this latter population, new modalities of drug development/access are needed. No significant financial relationships to disclose.