tbuckley/cabot-search huggingface dataset:
Abstract 13398: Assessment of a Continuous Monitoring Technique to Measure Adequacy of Respiration
Authors: Alexander Panasyuk, Michael Lalli, Svetlana Panasyuk, Nicole Yocum, Lynn Desmarais, Robert Lew, Jenny Freeman
Journal: Circulation (2011)

Abstract:   Objective:  Respiratory status is not adequately monitored in non-intubated patients. Decisions rely on O2 saturation, respiratory rate & subjective assessment. The more important objective parameter of minute ventilation is not measured. We evaluated a non-invasive, lead-based Respiratory Variation Measurement (RVM) which provides continuous, quantitative, real time assessment of tidal volume & minute ventilation.   Methods:  Respiratory signals from 5 anatomically determined lead configurations collected using an impedance-based RVM system were run through advanced algorithms (523 tests, 25 visits, 9 adult subjects). Simultaneous spirometry measurements (tidal volume & minute ventilation during normal breathing, slow breathing, erratic breathing) were obtained. RVM accuracy & precision were assessed compared to spirometry values.   Results:  RVM data correlated strongly with spirometer volume measurements in all breathing maneuvers. Across all subjects, median correlation, r, for the 5 lead configurations ranged from 0.88 -0.99, with a maximum of r = 0.99 for configuration “β”. A mixed effects ANOVA analysis (subject is a random effect) discriminated (p    Conclusions:  Lead placement & a calibration algorithm enable RVM data to be used to calculate tidal volume and minute ventilation. RVM shows promise to be a new clinical parameter of respiratory adequacy, providing an early indication of respiratory compromise and assisting clinical decision making regarding the necessity of intubation and earlier intervention. Use of RVM could improve resuscitation protocols and patient outcomes while reducing overall health care costs.
Isoprenoids modulate the expression of the amyloid precursor protein adaptor protein Fe65 in the human neuroblastoma cell line SH-SY5Y
Authors: Rebecca Nolan, Jan K. Teller
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4352 

Neuroblastoma is a relatively rare cancer that develops from the sympathetic system neuronal precursors. Solid tumors typically form in the abdomen and are most common in children. These tumors are often present at birth but are not diagnosed until symptoms occur months or years later therefore, at diagnosis the neuroblastoma has usually metastasized and prognosis declines. The undifferentiated human neuroblastoma cell line, SH-SY5Y, was used to investigate the changes in the amyloid precursor protein (APP) adaptor proteins, Fe65 and Mint1/X11α, in response to isoprenoids. Fe65 and Mint1/X11α are associated with APP, a protein at the forefront of Alzheimer’s disease pathogenesis of yet unknown physiological function. Fe65 binds to the APP intracellular domain and the LDL-receptor-related protein (LRP) which leads to alterations in transcription and intracellular signaling. Mint1/X11α is responsible for synaptic vesicle exocytosis when bound to Munc-18 and can inhibit the γ-secretase which cleaves APP. These adaptor proteins may act as molecular switches altering APP cleavage and subsequent signaling pathways. The regulation of the isoprenoid/cholesterol pathway is of interest in cell survival studies because isoprenoids are required by many proteins for insertion into the membrane for proper function. In our studies, the cholesterol and isoprenoid pathways were manipulated to determine the changes in Fe65 and Mint1 expression. We used complete (FBS) and lipoprotein-deficient serum (LDFBS) with simvastatin (SV), mevalonate or methyl-beta-cyclodextrin (MBCD), to assess distinct effects of isoprenoids and cholesterol. The statin drugs have been shown to inhibit proliferation and to induce apoptosis in a variety of tumor cells, including neuroblastoma. Fe65 was increased in a normal cholesterol (FBS) and normal isoprenoid (mevalonate rescued) environment in an SV dose-dependent manner. Interestingly, the cells in low cholesterol (LDFBS) had an inverse response to SV. This decrease was enhanced by the addition of mevalonate suggesting isoprenoids may regulate Fe65 in cultured SH-SY5Y. Mint1 did not respond to the changes in cholesterol/isoprenoids to the extent of Fe65. Current experiments will further define the role of the isoprenoids and cholesterol in the regulation of Fe65 and other APP adaptor proteins.
Abstract 18108: Decreased Fmo3 Expression is Associated With Increased Atherosclerosis and Impaired Liver Function in Apolipoprotein E Null Mice
Authors: Diana M Shih, Nam Che, Yonghong Meng, Judy Wu, Zeneng Wang, Yehudit Hasin, Simon W Beaven, J M Brown, Richard Lee, Mark J Graham, Stanely L Hazen, Aldons J Lusis
Journal: Circulation (2013)

Recent studies demonstrated a strong positive association between blood trimethylamine-N-oxide (TMAO) level and risk for cardiovascular disease. Dietary choline is converted to trimethylamine (TMA) by the gut bacteria, and TMA is then converted to TMAO in the liver, mainly by flavin containing monooxygenase 3 (Fmo3). To examine how FMO3 expression influences atherogenesis, we administered two different FMO3 or control antisense oligonucleotdies (ASOs) to apolipoprotein E (apoE) null mice for 15 weeks. During the last 12 weeks of the ASO treatment, the mice received a chow diet containing 1% choline to enhance TMA production. Hepatic FMO3 mRNA levels were decreased by 80% in mice that received either FMO3 ASO #1 or #2 versus those that received the control ASO. As expected, circulating TMA and TMAO levels were significantly increased and decreased, respectively, in the mice that received the two FMO3 ASOs versus the controls. Other observed changes in the FMO3 ASO-treated mice included: decreased plasma triglyceride, HDL, and glucose levels. Significantly increased VLDL/IDL/LDL cholesterol was observed only in FMO3 ASO #2-treated mice versus the controls. FMO3 ASO treatment increased circulating total bile acid levels by more than 2-fold. Compared to controls, serum markers of hepatic inflammation and necrosis (ALT, AST) were significantly increased in FMO3 ASO treated mice. Histological examination revealed obvious hepatic steatosis and increased inflammatory cell infiltration, suggesting that FMO3 abrogation may be a reasonable model for non-alcoholic steatohepatitis (NASH). We also found a significant increase in quantitative triglyceride and cholesterol content of these livers. Transcriptional profiling by microarrays showed increased hepatic expression of inflammatory genes in mice that received FMO3 ASOs versus the controls. In addition, a significant increase in spleen weight in these mice suggests increased systemic inflammation. Finally, FMO3 knockdown increased atherosclerosis by more than 50% when compared to controls (p &lt; 0.01). This work demonstrates that blocking FMO3 activity has a major impact on liver physiology and atherosclerosis. Our study suggests a protective role for FMO3 in atherosclerosis and liver function.
Abstract 13438: Additive Value of Free Wall Activation Delay for Risk Stratification of Cardiac Resynchronization Therapy Patients
Authors: Josef Marek, Mohamed Ahmed, Toshinari Onishi, Tetsuari Onishi, Stephanie C Haberman, Samir Saba, John Gorcsan
Journal: Circulation (2012)

Background: Free wall activation delay (FWAD) is a new simplified tissue Doppler index of mechanical dyssynchrony applied to free wall segments. Septal to posterior wall delay (SPWD) by speckle tra...
A Phase II Study Of Cyclophosphamide, Etoposide, Vincristine and Prednisone (CEOP) Alternating With Pralatrexate (P) As Front Line Therapy For Patients With Peripheral T-Cell Lymphoma (PTCL): Preliminary Results From The T- Cell Consortium Trial
Authors: Ranjana H. Advani, Stephen M. Ansell, Mary J Lechowicz, Anne W Beaven, Fausto R. Loberiza, Kenneth R Carson, Andrew M Evens, Francine M. Foss, Steven M. Horwitz, Barbara Pro, Lauren Pinter-Brown, Sonali M. Smith, Andrei R. Shustov, Kerry J. Savage, Julie M Vose
Journal: Blood (2013)
Cyclosporin neurotoxicity after chemotherapy
Authors: G. Pratt, B. Kennedy, G. Smith, M B Lewis, D. A Tweddle, K. P Windebank
Journal: BMJ (1999)

Children born after intracytoplasmic sperm injection What do authors mean by control infants?Editor-Sutcliffe et al compare babies born through intracytoplasmic sperm injection with control babies (matched for social class, maternal education, region, and sex) born after unassisted conception. 1 In their table they give means, standard deviations, and 95% confidence intervals for the two groups separately.These confidence intervals tell us about the estimation of the mean in the population of which the babies are a random sample, which they are not.They tell us nothing about the comparison between the cases and controls.These controls have been chosen to be similar to the study babies in many ways; they are not a representative sample of babies.It is the difference between the study babies and the control babies that is of interest, and the confidence interval we should have is that for this difference in mean.We cannot work this out from the data given, because this is a paired study and we have unpaired standard deviations.All we have for the comparison is the implication, not actually stated, that the differences are not significant.What we should be given are confidence intervals that tell us how different the cases and controls are.
Abstract 15256: The Effect of Pulmonary Regurgitation and Right Ventricular (RV) Dilatation on RV Strain Measurements: Need for Volumetric Correction of RV Deformation Measurements?
Authors: Andreea Dragulescu, Lars Grosse-Wortmann, Luc Mertens
Journal: Circulation (2011)

Background:  Pulmonary insufficiency (PI) with right ventricular (RV) dilatation is common after tetralogy of Fallot (ToF) repair. RV myocardial deformation is reduced in ToF patients but the PI-related RV dilatation and strain (S) and strain rate (SR) is not well studied.   Aim:  To evaluate the relationship between RV S and SR and PI-related RV dilatation.   Methods and results:  Sixty pts were studied: 40 pts after ToF repair and 20 age matched controls. All pts underwent an echocardiography at the time of a clinically indicated MRI. Ultrasound images were acquired using a GE Vivid 7 (GE Ultrasound, USA). For RV longitudinal deformation the RV lateral S and SR were obtained from an apical four chamber view using speckle tracking technique. Cardiac MRI was used to quantify RV volumes and pulmonary regurgitant volume (PRV). RV deformation parameters were significantly decreased in the ToF group compared to controls: S -22.8±4.7% vs -34±5.2%, p   Conclusion:  In ToF patients, RV dilatation is associated with reduced strain. Correcting RV deformation for RV dilatation theoretically could better represent RV function and the negative relationships between S/EDV and PRV suggest that progressive PI negatively affects RV function, irrespective of the effect of RV volume.
Successful treatment of Erdheim-Chester disease, a non-langerhans histiocytosis, with Interferon-alpha
Authors: F. S. Braiteh, C. Boxrud, B. Esmaeli, R. Kurzrock
Journal: Journal of Clinical Oncology (2005)

2539 Background: Erdheim-Chester disease is a rare non-Langerhans histiocytosis, with particular tropism for connective and adipose tissues. The infiltrative process preferentially involves the axial skeleton, pituitary, orbit, retroperitoneum, lung, mediastinum and central nervous system. To date, there is no standard treatment for this rare disorder and about two-thirds of the patients succumb to their disease within three years. Methods: We treated three patients with advanced Erdheim-Chester disease with interferon-α at a starting dose of 3 to 6 million units s.c. three times per week. All three patients were middle-aged men who were diagnosed with Erdheim-Chester disease based on clinical, radiological and pathological features. These patients had progressed despite radiation therapy, corticosteroids and chemotherapy. Patients suffered from painful osteosclerosis, diabetes insipidus and/or progression towards blindness due to retro-orbital disease. Results: All three patients demonstrated rapid improvement of symptoms and signs, including resolution of proptosis, improvement in diabetes insipidus, and/or regression of bone lesions accompanied by marked decrease in pain. Because of fatigue, the dose was lowered to one million units three times per week in all patients. This dose was tolerated with almost no side effects. Patients continued to improve on the lower dose and all three individuals have had a long-standing response (2.5+ to 4+ years). Conclusions: Our observations suggest that interferon-α has significant beneficial effects in Erdheim-Chester disease. No significant financial relationships to disclose.
Antitumor activity of OSI-930, a novel multi-targeted tyrosine kinase inhibitor, in combination with standard chemotherapeutics in preclinical cancer models
Authors: Mary Srebernak, Shannon Winski, David Emerson, Blake Tomkinson, Andrew Stephens, Andrew Crew, Andrew Flood, Paul Briner
Journal: Cancer Research (2005)

677   The full potential and optimal utilization of targeted kinase inhibitors in combination with standard chemotherapeutic regimens has yet to be realized. OSI-930 potently inhibited the closely-related kinases Kit, KDR, and PDGFRβ in cell-based assays (IC 50  values  .  A FOLFOX-like regimen (5-FU/ oxaliplatin) was selected for combination studies with OSI-930 in two human CRC models, SW48 and COLO 205. 5-FU was administered at 20 mg/kg IV Day 1-5, oxaliplatin at 10 mg/kg IP on Day 1, and vehicle or OSI-930 200 mg/kg PO administered as maintenance therapy Day 8-21. Treatment with maintenance OSI-930 resulted in enhanced tumor growth inhibition (TGI) and growth delay (GD) compared to vehicle maintenance in both tumor models (SW48: TGI=84.4% compared to 68.9%, GD=6.8 days over vehicle; COLO 205: TGI=70.8% compared to 28.4%, GD=12.4 days over vehicle). In a separate COLO 205 study, OSI-930 administered at 100 mg/kg PO either concomitantly (Day 1-14) or as maintenance therapy (Day 8-21) improved tumor growth delay by 2-3 fold and increased TGI by 15-20% compared to vehicle maintenance. Both dosing schedules were well-tolerated with body weight loss in both groups
Abstract P136: Tracheal Temperature for Monitoring Core Temperature during Mild Hypothermia in Pigs
Authors: Danica Krizanac, Moritz Haugk, Wolfgang Weihs, Michael Holzer, Keywan Bayegan, Andreas Janata, Fritz Sterz, Harald Herkner, Udo Losert, Anton Laggner, Wilhelm Behringer
Journal: Circulation (2008)

Purpose of the stud y: Early out-of-hospital induction of mild hypothermia after cardiac arrest needs an easy to use and accurate core temperature monitoring, which might be achievable with tracheal temperature measurement. The aim of the study was to evaluate which tracheal temperature site (Ttra) reflects best pulmonary artery temperature (Tpa) during the induction of mild hypothermia. Methods: Eight pigs (29 –38 kg) were anesthetized and intubated with a specially designed endotracheal tube with three temperature probes: Ttra1 was attached to the wall of the tube, 1 cm proximal to the cuff-balloon, without contact to the mucosa; Ttra2 and Ttra3 were placed on the cuff-balloon with tight contact to the mucosa, whereas Ttra3 was covered by a plastic tube to protect the mucosa. Core temperature was measured with a pulmonary artery catheter (Tpa). Pigs were cooled with a new surface cooling device (Emcoolspad®, Vienna, Austria). Data are presented as mean (±SD), and mean differences (95% CI). Results: Emcoolspad® decreased Tpa from 38.5°C to 33°C in 31±10 min, which translates into a cooling rate of 11.9±3.8°C/h. Overall mean differences of tracheal temperatures to pulmonary artery temperature (Tpa) are shown in table 1 . Ttra 1 showed the least difference to Tpa, followed by Ttra 2 and Ttra 3. There was a significant difference in temperature differences (Ttra-Tpa) related to temperature measurement site on the tracheal tube (p&lt;0.007). Conclusions: The temperature probe proximal of the cuff (Ttra 1) reflects best pulmonary artery temperature. It seems to be an accurate surrogate for core temperature during the induction of mild hypothermia. The industry is asked to provide a tracheal tube with a temperature sensor for simple temperature monitoring during fast cooling to facilitate the implementation of mild hypothermia after cardiac arrest in the out-of-hospital setting.
Abstract 5170: The autotaxin-lysophosphatidic acid signaling pathways in ovarian carcinoma
Authors: Hadil Onalla, Claes Tropé, Reuven Reich, Ben Davidson
Journal: Cancer Research (2015)

Abstract Ovarian carcinoma ranks as the fifth most common cancer among women. This is attributed to late presentation of the patients. The disease is characterized by widespread intraperitoneal metastases and accumulation of effusion fluids mainly in the peritoneal cavity Lysophosphatidic acid (LPA) is a bioactive phospholipid with mitogenic and growth factor-like activities affecting cell invasion, cancer progression and resistance that act via specific cell-surface receptors present in many transformed cell types. LPA is produced by two main pathways, by PLA-2 and by Autotaxin (LysoPLD). Once its produced, it acts on six specific G protein coupled receptors, LPAR1-6. LPA has recently been implicated as a growth factor present in ascites of ovarian cancer patients. Previous studies have shown high levels of LPA in the effusions of ovarian carcinoma patients. The aim of our study was to examine the role of ATX-LPA signaling in the progression of serous ovarian carcinoma. A total of 230 samples of serous ovarian carcinoma from the three different anatomic sites of the disease, were used .Effusion fluids were frozen and stored separately. All specimens were submitted for routine diagnostic purpose to the Division of Pathology at the Norwegian Radium Hospital during the period 1998-2008. mRNA levels of the six different LPA receptors were measured by RT-PCR, protein levels of Autotaxin were measured by Western blotting. Results show that LPA2R is higher in effusion-derived tumor cells compared to solid lesions (p&amp;lt;0.001), while the opposite was found for LPA3R (p&amp;lt;0.001) and LPA6R (p&amp;lt;0.001). Clinico-pathological analysis showed that LPA3R levels are significantly higher in pre-chemo patients (p = 0.038). LPA2R (p = 0.021) and LPA5R (p = 0.035) were found higher in cases with larger residual disease volume. LPA5R (p = 0.032) was higher in cases with primary chemo-resistance and LPA1R (p = 0.05) was marginally associated with better overall survival. Autotaxin protein levels were lower in effusion-derived tumor cells compared to solid lesions (p&amp;lt;0.001), yet higher levels of Autotaxin were found in peritoneal lesions compared to pleural ones (p = 0.033). In this study we showed significant changes in mRNA LPAR levels and Autotaxin protein levels with the progression of the disease that correlates to clinic-pathological parameters. To our best knowledge, this is the first description of the ATX-LPA signaling pathway in ovarian carcinoma with clinical relevance. Citation Format: Hadil Onalla, Claes Tropé, Reuven Reich, Ben Davidson. The autotaxin-lysophosphatidic acid signaling pathways in ovarian carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5170. doi:10.1158/1538-7445.AM2015-5170
Abstract 15545: Incremental Prognostic Value of Echocardiographic Markers of Left Ventricular Remodeling and Diastolic Function in the Surgical Treatment for Ischemic Heart Failure Trial
Authors: Grace Lin, Lilin She, Kerry Lee, Rafal Dabrowski, Paul Grayburn, Miroslaw Rajda, David Prior, Patrice Desvigne-Nickens, William Zoghbi, Diane Miller, Michele Senni, Guglielmo Stefanelli, William Hathaway, Cesare Beghi, Thao Hyunh, Eric Velazquez, Jae Oh
Journal: Circulation (2014)

Introduction: Whether echocardiographic (echo) markers of left ventricular (LV) remodeling and diastolic dysfunction contribute incremental and independent prognostic information to clinical risk markers in patients (Pts) with coronary artery disease and severe LV systolic dysfunction is unclear. We sought to determine which echo variables provide the greatest prognostic value in the Surgical Treatment for Ischemic Heart Failure (STICH) population. Methods: Pts enrolled in STICH for whom transmitral Doppler (E/A ratio) was available on a baseline echo interpreted by an echo core laboratory blinded to treatment and outcomes formed the analysis cohort. Comprehensive datasets to account for missing echo data were created by multiple imputation and the impact on all-cause mortality was determined with the Cox’s regression model. Results: E/A ratio could be measured in 1511 of the 2136 Pts enrolled in STICH. Amongst markers of diastolic dysfunction, E/A ratio was the most significant predictor of mortality (χ 2 41.05, p &lt;0.001) with a non-linear, u-shaped, relationship. Mortality was lowest with E/A ratio = 1.0, and increased for E/A ratio &lt;0.6 and &gt;1.0 up to 2.3, beyond which there was no further increase in risk. The combination of larger LV end-systolic volume index (LVESVI), low or high E/A ratio, and mitral regurgitation severity grade, had highly significant incremental negative effects on mortality (χ 2 69.65, p&lt;0.001) when added to a multivariable model with clinical risk markers. Overall, creatinine (χ 2 30.00, p &lt;0.001), followed by LVESVI (χ 2 27.26, p&lt;0.001), age, and E/A ratio (χ 2 12.46, p&lt;0.001) were among the most significant predictors of mortality and accounted for 74% of the total prognostic information. LVESVI and E/A ratio were stronger predictors of poor prognosis than New York Heart Association (NYHA) functional class, hemoglobin, diabetes, stroke, or atrial fibrillation. Conclusions: Echo markers of advanced LV remodeling and diastolic dysfunction add incremental prognostic value to clinical risk markers and are more predictive of poor prognosis than advanced NYHA functional class or anemia. LVESVI and E/A ratio outperformed other echo markers and should be considered standard in assessing risk in Pts with ischemic LV dysfunction.
Abstract 2126: Risk Stratification After Reperfused Acute Myocardial Infarction Using Contrast-enhanced Cardiovascular Magnetic Resonance: Comparison Of First-pass And Delayed Enhancement Imaging
Authors: Matthias Regenfus, Carolin Stingl, Michael Schmid, Michaela Schmidt, Josef Ludwig, Werner G Daniel
Journal: Circulation (2007)

The established parameter for risk stratification after reperfused acute myocardial infarction (MI) is left ventricular (LV) ejection fraction (EF). With the use of contrast-enhanced cardiovascular...
Collagen But Not Fibrinogen Surfaces Induce Bleb Formation, Exposure of Phosphatidylserine, and Procoagulant Activity of Adherent Platelets: Evidence for Regulation by Protein Tyrosine Kinase-Dependent Ca2+ Responses
Authors: Johan W.M. Heemskerk, Wim M.J. Vuist, Marion A.H. Feijge, Chris P.M. Reutelingsperger, Theo Lindhout
Journal: Blood (1997)