tbuckley/cabot-search huggingface dataset:
Abstract 5500: Nanoparticle Inhalation Impairs Endothelium-dependent Vasoreactivity in Coronary Arterioles
Authors: Amanda J LeBlanc, Yanduan Hu, Judy M Muller-Delp, B. T Chen, D. Frazer, V. Castranova, Timothy R Nurkiewicz
Journal: Circulation (2008)

Epidemiological studies have shown that exposure to particulate matter (PM) is associated with an increased risk for myocardial infarction (MI). We have recently shown that systemic microvascular function is significantly impaired after inhalation exposure to PM and nanoparticles. However, it remains unclear how endothelial function in the coronary microcirculation responds to such insults and if impaired vasoreactivity as a result of exposure contributes to the increased risk for MI. Male Sprague-Dawley rats were exposed to filtered air (control), fine TiO 2 particles (primary particle diameter, ~1μm), or TiO 2 nanoparticles (primary particle diameter, ~21 nm) via inhalation at concentrations relevant to ambient air pollution (Fine TiO 2 , ~ 8–90 μg measured pulmonary deposition; nano-TiO 2 , ~ 4–38 μg measured pulmonary deposition). Coronary arterioles (≤ 150 μm in diameter) were isolated from the left anterior descending artery distribution and responses to flow (FID), acetylcholine (ACh), endothelin and dea-NONO-ate were assessed. Exposure to either fine TiO 2 or nano-TiO 2 impaired endothelium-dependent FID (Control 78±8%, Fine TiO 2 62±5%, Nano-TiO 2 60±8%). Similarly, endothelium-dependent vasodilation to ACh tended to be lower in coronary arterioles from rats exposed to fine TiO 2 and nano-TiO 2 compared to arterioles from control rats, but this did not reach statistical significance. Interestingly, vascular smooth muscle nitric oxide (NO) sensitivity (dea-NONO-ate) was decreased by exposure to nano-TiO 2 , but not fine TiO 2 (Nano-TiO 2 36±8%, Fine TiO 2 69±5%). Furthermore, nano-TiO 2 exposure diminished vasoconstrictor responses to endothelin, whereas fine TiO 2 exposure had no effect on endothelin reactivity (Nano-TiO 2 65±6%, Fine TiO 2 80±4%). These results suggest that nanoparticle exposure causes significantly more microvascular dysfunction than exposure to fine TiO 2 . It is probable that such disturbances in coronary microvascular function contribute to the cardiac events associated with particle pollution exposure. Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the National Institute for Occupational Safety and Health.
The Effect of Finasteride in Men with Benign Prostatic Hyperplasia
Authors: Glenn J. Gormley, Elizabeth Stoner, Reginald C. Bruskewitz, Julianne Imperato-McGinley, Patrick C. Walsh, John D. McConnell, Gerald L. Andriole, Jack Geller, Bruce R. Bracken, Joyce S. Tenover, E. Darracott Vaughan, Frances Pappas, Alice Taylor, Bruce Binkowitz, Jennifer Ng
Journal: New England Journal of Medicine (1992)

Benign prostatic hyperplasia is a progressive, androgen-dependent disease resulting in enlargement of the prostate gland and urinary obstruction. Preventing the conversion of testosterone to its tissue-active form, dihydrotestosterone, by inhibiting the enzyme 5α-reductase could decrease the action of androgens in their target tissues; in the prostate the result might be a decrease in prostatic hyperplasia and therefore in symptoms of urinary obstruction.
Abstract 3315: Therapeutic Implications of Sympathetic Stimulus in Orthostatic Patients: Measured by Spectral Domain Analysis
Authors: Rohit Arora, Elif Aysin, Ben Aysin, Joe Colombo
Journal: Circulation (2007)

Upon assuming an upright, head up posture, a sympathetic surge is expected. Sympathetic Withdrawal (SW) is abnormal and can differentiate Orthostasis. SW, with blood pressure (BP) and heart rate (HR), can fully define the continuum that is Orthostasis, including pre-clinical forms: Orthostatic Hypotension (OH-), Orthostatic Intolerance (OI), Orthostatic Hypertension (OH+), and Postural Orthostatic Tachycardia Syndrome (POTS). Our objective was to test the therapeutic implications of SW in Orthostatic patients. Autonomic profiling of 210 consecutive Orthostatic patients recruited from ambulatory clinics was performed using the ANX-3.0 Autonomic Monitoring System (Ansar, Inc., Philadelphia, PA). The cohort (age=58.9±11.6; 30 Diabetics; 132 Females, 28 Controls) was followed over a two year period. Autonomic profiling was based on patient responses to a standard clinical study that includes a resting baseline and periods of deep (relaxed) breathing, short Valsalva maneuvers, and quick stand immediately followed by quiet standing. The control group were patients with known diagnoses. The experimental group were prescribed 2.5 mg Midodrine once a day around dinner. Control patients were administered Flourinef, or support hose, or when possible were requested to modify their diets to add salt and build fluid volume. Patients with dysautonomia, with symptoms of elevated BP when supine were omitted from the study. In 89% of the experimental cases, SW was reversed in approximately 6 months and weaned from the medication. The remaining cases were reversed and weaned before the end of the two year follow up. In the control group, 46% of the patients on Flourinef, 4% of the support hose patients and 12% of the diet modification patients corrected SW within the two year period. The application of an alpha-adrenergic agonist seems to have greater efficacy than a mineralo-corticoid, mechanical intervention, or dietary modification in correcting SW associated with Orthostasis.
HLA Haplotype Frequency Analysis Within India: Pre-Requisite For Bone Marrow Donor Registry and Cord Blood Bank Planning
Authors: Martin Maiers, Michael Halagan, Nicole Leahy, Sangeeta Joshi, H Sudarshan Ballal, Latha Jagannathan, Sharat Damodar, Periathiruvadi Srinivasan, Saranya Narayan, Navin Khattry, Pankaj Malhotra, Sandip A Shah, Raghu Rajagopal, Nezih Cereb, Soo Young Yang, Leenam Dedhia, Sunil Parekh, Joy J Mammen, Dolly Daniels, Daniel J. Weisdorf
Journal: Blood (2013)
Functional magnetic resonance imaging of schizophrenic patients and comparison subjects during word production
Authors: D A Yurgelun-Todd, C M Waternaux, B M Cohen, S A Gruber, C D English, P F Renshaw
Journal: American Journal of Psychiatry (1996)

This study was undertaken to test the feasibility of using functional magnetic resonance imaging (MRI) to examine changes in cortical activation in response to verbal tasks in two brain regions.Twelve schizophrenic patients and 11 comparison subjects underwent functional MRI of the frontal and temporal lobes. Stimulus sequences were divided into five 30-second segments by using a task-activation paradigm that alternated between resting and stimulated states. Functional images were collected every 30 seconds by using a gradient echo pulse sequence.Schizophrenic subjects demonstrated significantly less left frontal activation and greater left temporal activation than comparison subjects during a word fluency task.These preliminary data suggest that functional MRI has the sensitivity to detect differences in activation between comparison subjects and schizophrenic patients during higher cortical functions. These findings are in agreement with PET studies that reported reduced left frontal activation during challenge paradigms for the schizophrenic patients.
Abstract 16778: Atherosclerotic Plaque Distribution Pattern and Burden in the Carotid and Iliac-Femoral Territories Assessed by 2D/3D Ultrasound in Middle-Aged Population. The PESA (Progression and Early Detection of Subclinical Atherosclerosis) Study
Authors: Luis J Jimenez-Borreguero, Leticia Fernandez-Friera, Jose L Pernalvo, Vicente Martinez, Gabriela Guzman, Eliseo Guallar, Henrik Sillesen, Borja Ibanez, Jose M Ordovas, Agustin Mocoroa, Gines Sanz, Antonio Fernandez-Ortiz, Valentin Fuster
Journal: Circulation (2013)

Background: The significance of subclinical atherosclerosis in both carotid and iliac-femoral territories is not yet clear. A better characterization of the burden and distribution pattern in diffe...
Midostaurin (PKC412) Demonstrates a High Rate of Durable Responses in Patients with Advanced Systemic Mastocytosis: Results from the Fully Accrued Global Phase 2 CPKC412D2201 Trial
Authors: Jason Gotlib, Hanneke C. Kluin-Nelemans, Tracy I. George, Cem Akin, Karl Sotlar, Olivier Hermine, Farrukh Awan, Elizabeth O Hexner, Michael Mauro, David Sternberg, Matthieu Villeneuve, Fabienne Emery-Salbert, Eric Stanek, Karin Hartmann, Hans-Peter Horny, Peter Valent, Andreas Reiter
Journal: Blood (2014)
Train relatives to intervene
Authors: C. A J McLaughlan
Journal: BMJ (1994)

We report an unusual complication after thrombo- lysis was given to a patient in whom the diagnosis was wrong.A 34 year old man was transferred from a district hospital to our invasive care unit because of haemodynamic instability after thrombolytic treat- ment for acute myocardial infarction.Acute myocardial infarction had been diagnosed on the basis of 1 mm horizontal elevation of the ST segment in leads II and III and AVF and decreased pain after sublingual nitrates.On arrival in the intensive care unit the patient was complaining of epigastric and left upper abdominal pain that radiated to his shoulder.He was pale and sweating, with blood pressure 120/80 mm Hg and pulse rate 130/min.The lungs were clear, and, except for the tachycardia, an examination of the heart yielded normal findings.Curiously, deep abdominal palpation was asso- ciated with moderate pain in the left upper abdomen.An electrocardiogram showed a sinus tachycardia of 120 beats/min.The patient was given intravenous morphine, and his pain disappeared almost completely.
Abstract 2800: Non-Invasive Quantification of Complete Left-Ventricular Pressure-Volume Loops in Patients with Cardiac Overload
Authors: Dirk W Donker, Paul G Volders, Harry J Crijns, Theo Arts
Journal: Circulation (2007)

Pressure-volume relations of the left ventricle (LV) allow comprehensive assessment of systolic and diastolic LV function. Non-invasive assessment of LV function is currently based on, but limited ...
Abstract 3430: Left Ventricular Hypertrophy and Diastolic Dysfunction in Mice Lacking All Nitric Oxide Synthase Isoforms
Authors: Masato Tsutsui, Kiyoko Shibata, Hiroaki Shimokawa, Yasuko Yatera, Yumi Furuno, Sei Nakata, Ken Sabanai, Tsuyoshi Morishita, Hiromi Tasaki, Yasuhide Nakashima, Nobuyuki Yanagihara, Yutaka Otsuji
Journal: Circulation (2008)

We have recently succeeded in developing mice in which all three nitric oxide synthase isoforms (nNOS, iNOS, and eNOS) are completely disrupted ( PNAS 2005). In this study, we examined cardiac morphology and function in those mice. Cardiac echocardiography and left ventricular (LV) hemodynamic measurement were performed in male wild-type (WT), singly nNOS −/− , iNOS −/− , eNOS −/− , and triply n/i/eNOS −/− mice at 2 and 5 months of age (n=5–8). At 2 months of age, no significant cardiac morphological or functional changes were detected in any strains studied. However, at 5 months of age, significant LV hypertrophy (wall thickness, mm) were noted in the triply n/i/eNOS −/− mice (1.3±0.1, P &lt;0.01) and to a lesser extent in the singly eNOS −/− mice (1.1±0.1, P &lt;0.05), but not in the singly nNOS −/− (0.8±0.1) or iNOS −/− mice (1.0±0.1), as compared with the WT mice (1.0±0.2). Furthermore, significant LV diastolic dysfunction (as evaluated by echocardiographic E/A ratio and by hemodynamic peak negative dP/dt), with preserved LV systolic function (as assessed by echocardiographic ejection fraction and by hemodynamic peak positive dP/dt), was noted only in the 5-month-old triply n/i/eNOS −/− mice (2.7±0.1 and 2505±60, both P &lt;0.05), but not in any singly nNOS −/− (2.1±0.2 and 3833±402), iNOS −/− (2.0±0.1 and 3773±747), or eNOS −/− mice (2.0±0.3 and 2934±122), as compared with the WT mice (1.9±0.1 and 4038±344). In addition, significant cardiac fibrosis (fibrosis area, %, Masson-trichrome staining) was also detected only in the 5-month-old triply n/i/eNOS −/− mice (1.4±0.2, P &lt;0.05) compared with the WT mice (0.3±0.1). Importantly, arterial blood pressure (mmHg, tail-cuff method) was significantly elevated in the triply n/i/eNOS −/− (143±3.1, P &lt;0.05) than in the WT mice (104±7.3), but the hypertensive level was comparable to that in the singly eNOS −/− mice (140±8.5). Thus, mechanism(s) other than hypertension appears to be involved in the cardiac abnormalities of the triply n/i/eNOS −/− mice. These results provide the first evidence that genetic disruption of all NOSs results in LV hypertrophy and diastolic dysfunction in mice in vivo, suggesting a pivotal role of the NOS system in maintaining cardiac homeostasis.
Electromagnetic guidance for catheter-based transendocardial injection: a platform for intramyocardial angiogenesis therapy
Authors: Ran Kornowski, Martin B Leon, Shmuel Fuchs, Yoram Vodovotz, Michael A Flynn, David A Gordon, Anthony Pierre, Imre Kovesdi, Joan A Keiser, Stephen E Epstein
Journal: Journal of the American College of Cardiology (2000)
Abstract 16183: Inhibition of Hcn Overexpression in Failing Heart of Dilated Cardiomyopathy Mouse Model by Ivabradine Prevents Sudden Arrhythmic Death
Authors: Yoshihiro Kuwabara, Koichiro Kuwahara, Makoto Takano, HIdeyuki Kinoshita, Yasuaki Nakagawa, Satoru Usami, Shinji Yasuno, Kazuhiro Nakao, Takeya MInami, Yuko Yamada, Chinatsu Yamada, Junko Shibata, Toshio Nishikimi, Kenji Ueshima, Kazuwa Nakao
Journal: Circulation (2011)

Growing evidence demonstrates that the hyperpolarization-activated cyclic nucleotide-gated channels (HCN) expression is increased in failing hearts and potentially involved in the increased arrythm...
Abstract 637: Utilization of Retrograde Right Bundle Branch Block to Differentiate Atrio Ventricular Nodal from Accessory Pathway Conduction
Authors: Suraj Kapa, Benhur Henz, Chadi Dib, Yong-Mei Cha, Paul A Friedman, Thomas M Munger, Dorothy J Ladewig, Stephen C Hammill, Douglas L Packer, Samuel J Asirvatham
Journal: Circulation (2008)

Determining whether retrograde ventriculoatrial (VA) conduction is through the AV node (AVN) or an accessory pathway (AP) is critical for successful ablation of supraventricular tachycardia (SVT). With introduction of ventricular extrastimuli (VEST), retrograde right bundle branch block (retro RBBB) may occur and result in abrupt VH interval prolongation. We hypothesized when retrograde conduction is via an AP, VA interval change is less than VH interval change, whereas with retrograde AVN conduction, VA interval change is equal to or greater than VH interval change. We retrospectively reviewed the electrophysiology (EP) studies of patients undergoing ablation for AVNRT (n=55) or AVRT (n=50). The intracardiac electrograms were reviewed for induction of retro RBBB and change in VH and VA intervals during VEST. Parahisian pacing, decremental pacing, arrhythmia diagnosis and ablation outcomes were reviewed. All results were found to be reproducible between two independent observers with inter and intra observer reliability scores of 1.00 for identification of retro RBBB and greater than 0.85 for measurement of VH and VA intervals. Of 105 patients, 84 (80%) had evidence of induced retro RBBB during VEST. The average VH interval increase with induction of retro RBBB was 53.7 ms for patients with retrograde AP conduction and 54.4 ms for patients with AVN conduction (p=ns). The average VA interval increase with induction of retro RBBB was 13.6 ms with AP conduction and 70.1 ms with AVN conduction (P &lt; 0.001). All patients with a greater VH than VA interval change had a final diagnosis of AVRT and those with a VH change less than VA change had AVNRT, yielding sensitivity and specificity of 100%. Using a cutoff of 50 ms for change in VA interval with onset of retro RBBB to diagnose AVNRT accurately identified AVNRT in 100% and AVRT in 95%. Induction of retro RBBB during VEST is common during EP studies for SVT. The relative change in the VH and VA intervals during retro RBBB accurately differentiates retrograde AVN from retrograde AP conduction with strong predictive accuracy. The use of retro RBBB based intervals is a useful technique facilitating the diagnosis of SVT in the EP laboratory, even in the absence of inducible tachycardia.
A novel mechanism for NETosis provides antimicrobial defense at the oral mucosa
Authors: Tirthankar Mohanty, Jonathan Sjögren, Fredrik Kahn, Anas H. A. Abu-Humaidan, Niels Fisker, Kristian Assing, Matthias Mörgelin, Anders A. Bengtsson, Niels Borregaard, Ole E. Sørensen
Journal: Blood (2015)

Neutrophils are essential for host defense at the oral mucosa and neutropenia or functional neutrophil defects lead to disordered oral homeostasis. We found that neutrophils from the oral mucosa harvested from morning saliva had released neutrophil extracellular traps (undergone NETosis) in vivo. The NETosis was mediated through intracellular signals elicited by binding of sialyl Lewis(X) present on salival mucins to l-selectin on neutrophils. This led to rapid loss of nuclear membrane and intracellular release of granule proteins with subsequent neutrophil extracellular trap (NET) release independent of elastase and reduced NAD phosphate-oxidase activation. The saliva-induced NETs were more DNase-resistant and had higher capacity to bind and kill bacteria than NETs induced by bacteria or by phorbol-myristate acetate. Furthermore, saliva/sialyl Lewis(X) mediated signaling enhanced intracellular killing of bacteria by neutrophils. Saliva from patients with aphthous ulcers and Behçet disease prone to oral ulcers failed to induce NETosis, but for different reasons it demonstrated that disordered homeostasis in the oral cavity may result in deficient saliva-mediated NETosis.
CAD Detection in Patients With Intermediate-High Pre-Test Probability
Authors: Nuno Bettencourt, Nuno Dias Ferreira, Daniel Leite, Mónica Carvalho, Wilson da Silva Ferreira, Andreas Schuster, Amedeo Chiribiri, Adelino Leite-Moreira, José Silva-Cardoso, Eike Nagel, Vasco Gama
Journal: JACC. Cardiovascular imaging (2013)
Iron, Expression of the Pattern Recognition Receptor-Inflammasome System, and Early Death in Adults with Sickle Cell Disease
Authors: Eduard J. van Beers, Yanqin Yang, Nalini Raghavachari, Xin Tian, Darlene Allen, James S. Nichols, Laurel Mendelsohn, Sergei A. Nekhai, Victor R. Gordeuk, James G. Taylor VI, Gregory J. Kato
Journal: Blood (2014)
Recent decline may be relatively late stage of long term process
Authors: M. Joffe
Journal: BMJ (1996)

students and not therefore classed.This is an exceptionally skewed population and not appropriate as a basis for drawing general conclusions.The authors' selective quotation from the world literature is unfortunate.They could have quoted papers from countries where there has been no decline in semen quality.Their reference to Carlsen et als paper is also selective.2Most serious reanalyses of the data in that paper suggest that no decline has occurred in the past 30 years.What is in dispute is why figures in the 20 years before that seem to have been higher.The factors that influence sperm quality are numerous, and the variability of specimens is considerable.Unless authors base their results on large studies and control for the many confounding variables then their contribution to our understanding of the problem is likely to be modest at best and in some cases misleading.
Abstract 190: HSP27 is Sufficient and Required for Prevention of Tachycardia Induced Remodeling in a Cell Model for Tachypacing
Authors: Bianca J Brundel, XiaoYan Qi, Yung-Hsin Yeh, Akiko Shiroshita-Takeshita, Denis Chartier, Robert H Henning, Harm H Kampinga, Stanley Nattel
Journal: Circulation (2006)

We previously found evidence that heat shock protein (HSP) induction protects against the promotion of atrial fibrillation (AF) by atrial tachypacing-remodeling in dogs. In this study, we evaluated the effect of HSP induction in a tachypaced atrial cell-line (HL-1) model of tachycardia-remodeling. Methods: The effects of tachypacing HL-1 myocytes (3 Hz, 0 – 4 hrs) on Ca 2+ transients (CaT) and cell shortening (CS), were studied with and without HSP-inducing pre-treatments like mild heat shock (HS), or the non-toxic inducer geranylgeranylacetone (GGA), transient transfection of human HSP70, HSP27, a phosphorylation deficient mutant HSP27-AAA or the phospho-mimicking mutant HSP27-DDD. Knockdown of HSP27 was performed with short-hairpin forming siRNA. Results: In HL-1 myocytes, tachypacing significantly and progressively reduced CaT and CS after 4 hours (Fig A ). HSP induction by HS or GGA protected HL-1 myocytes against suppression of CaT and CS by 4 hours of tachypacing. Protective effects were also seen upon transfection with HSP27 and a phosphorylation-mimicking HSP27 mutant, but not by HSP70 or a non-phosphorylatable HSP27-mutant construct (Fig B ). Knockdown of HSP27 with shRNA prevented GGA-mediated protection (Fig C ). Conclusions: Our findings indicate that HSP27 induction protects against AF-promoting remodeling, that the protective effect requires HSP27 phosphorylation, and HSP27 is sufficient for protection. These findings advance our understanding of the biochemical determinants of the protective effects of HSP induction against atrial tachycardia remodeling.
A phase I study of reolysin given intravenously to patients with advanced malignancies
Authors: L. Vidal, H. Pandha, J. Spicer, K. J. Harrington, S. Allen, D. Leader, M. Coffey, B. Thompson, S. Kaye, J. De-Bono
Journal: Journal of Clinical Oncology (2006)

3064 Background: Reovirus is a double-stranded RNA virus with minimal pathogenicity in humans that selectively replicates in cells with activated Ras. Activated Ras inhibits the anti-viral effects of double stranded RNA-activated protein kinase (PKR). Reovirus serotype 3 Dearing has selective antitumor activity, in vitro and in tumour xenograft models. Methods: Reolysin was administered as a 1-hr IV infusion every 4-weeks initially for one day; then 3 days then 5-days every 4 weeks. The starting dose was 1×108 tissue culture infectious dose (TCID50) increasing in successive cohorts until observation of drug-related toxicity ≥ grade 2. Endpoints were safety, viral replication, viral shedding, evaluation of immune response and antitumor activity. Results: 24 patients (pts) (median age 60; ECOG 1, 16 males) have been entered into the first 7 cohorts at the following dose levels: 1×108 for 1-day, 1×108 for 3-days and 1×108, 3×108, 1×109, 3×109 and 1×1010 TCID50 for 5-days. A maximum tolerated dose (MTD) has not been reached and no dose-limiting toxicities have been observed. Toxicities have been mild (grade 1 or 2) and have included chills, fever, headache, runny nose, fatigue and myelosuppression. Reverse transcription polymerase chain reaction (RT-PCR) studies of blood, urine, stool and sputum post reovirus administration were negative for viral shedding for all treated pts. All but one pt had neutralising anti-reovirus antibodies detectable pre-treatment. Titres increased after 1-week of treatment and remained high during subsequent courses of treatment. Two pts with metastatic colorectal cancer treated at 3×108 and 3×109 TCID50 had CEA tumour marker reduction by 60% and 27% receiving 6 and 3 courses of treatment respectively. One pt with metastatic pancreatic cancer received 4 courses of treatment with stable disease. One pt with metastatic prostate cancer had a 50% decrease in PSA after treatment at 3×109 TCID50, with evidence of tumor necrosis on CT scanning. Intratumoral reovirus replication has been detected by electron microscopy in tumur biopsies. Conclusions: Reolysin is well tolerated with minimal toxicity. No viral shedding has been detected. Virus-induced tumor necrosis associated with intratumor viral replication after systemic delivery has been observed. [Table: see text]
Host, disease, and antiretroviral factors are associated with normalization of the CD4:CD8 ratio after initiating antiretroviral therapy
Authors: Alan Winston, Sophie Jose, Martin Fisher, John Walsh, Mark Nelson, Richard Gilson, Frank Post, Margaret Johnson, Clifford Leen, David Chadwick, Phillip Hay, Jillian Pritchard, Anjum Tariq, Caroline Sabin
Journal: Journal of Allergy and Clinical Immunology (2015)