tbuckley/cabot-search huggingface dataset:
Bcar1/p130Cas Protein and Primary Breast Cancer: Prognosis and Response to Tamoxifen Treatment
Authors: Silvia van der Flier, Arend Brinkman, Maxime P. Look, Elisabath M. Kok, Marion E. Meijer-van Gelder, Jan G. M. Klijn, Lambert C. J. Dorssers, John A. Foekens
Journal: JNCI Journal of the National Cancer Institute (2000)

The product of the Bcar1/p130Cas (breast cancer resistance/p130Crk-associated substrate) gene causes resistance to antiestrogen drugs in human breast cancer cells in vitro. To investigate its role in clinical breast cancer, we determined the levels of Bcar1/p130Cas protein in a large series of primary breast carcinomas.We measured Bcar1/p130Cas protein in cytosol extracts from 937 primary breast carcinomas by western blot analysis. The levels of Bcar1/p130Cas protein were tested for associations and trends against clinicopathologic and patient characteristics, the lengths of relapse-free survival and overall survival (n = 775), and the efficacy of first-line treatment with tamoxifen for recurrent or metastatic disease (n = 268).Bcar1/p130Cas levels in primary tumors were associated with age/menopausal status and the levels of estrogen receptor and progesterone receptor. In univariate survival analysis, higher Bcar1/p130Cas levels were associated with poor relapse-free survival and overall survival (both two-sided P =.04; log-rank test for trend). In multivariate analysis, a high level of Bcar1/p130Cas was independently associated with poor relapse-free survival and overall survival. The response to tamoxifen therapy in patients with recurrent disease was reduced in patients with primary tumors that expressed high levels of Bcar1/p130Cas. In multivariate analysis for response, Bcar1/p130Cas was independent of classical predictive factors, such as estrogen receptor status, age/menopausal status, disease-free interval, and dominant site of relapse.Patients with primary breast tumors expressing a high level of Bcar1/p130Cas protein appear to experience more rapid disease recurrence and have a greater risk of (intrinsic) resistance to tamoxifen therapy. Thus, measurement of Bcar1/p130Cas may provide useful prognostic information for patients with primary or metastatic breast cancer.
Survival of lung adenocarcinoma patients with malignant pleural effusion
Authors: Shang-Gin Wu, Chong-Jen Yu, Meng-Feng Tsai, Wei-Yu Liao, Chih-Hsin Yang, I-Shiow Jan, Pan-Chyr Yang, Jin-Yuan Shih
Journal: European Respiratory Journal (2012)

In the era of targeted therapy, the association between lung adenocarcinoma patient survival and malignant pleural effusions (MPEs) remains unclear. This study investigated the clinical characteristics, survival and epidermal growth factor receptor (EGFR) gene ( EGFR ) mutation status of lung adenocarcinoma patients with MPE. From June 2005 to December 2010, consecutive pleural effusions were collected prospectively. Patient clinical characteristics, EGFR mutation status, and overall survival were analysed. We collected MPEs from 448 patients in stage IV lung adenocarcinoma at initial diagnosis. Median overall survival for patients with MPEs at initial diagnosis and following disease progression were 14.3 months and 21.4 months, respectively (p=0.001). There were 296 (66.1%) patients harbouring EGFR mutations, the mutation rates among patients with an MPE at initial diagnosis and one following disease progression were 68.2% and 56.6%, respectively (p=0.044); the L858R mutation rate was also higher among the former (32.6% versus 18.1%; p=0.009). Multivariate analysis revealed that patients who: developed MPEs following disease progression, harboured EGFR mutations, and received EGFR-tyrosine kinase inhibitor therapy, had longer overall survival. Patients in stage IV lung adenocarcinoma with MPEs at initial diagnosis have shorter overall survival and higher EGFR mutation rate, especially for L858R, than patients who develop MPEs following disease progression.
1189 ONCE-DAILY NS5A INHIBITOR (BMS-790052) PLUS PEGINTERFERON-ALPHA-2A AND RIBAVIRIN PRODUCES HIGH RATES OF EXTENDED RAPID VIROLOGIC RESPONSE IN TREATMENT-NAIVE HCV-GENOTYPE 1 SUBJECTS: PHASE 2A TRIAL
Authors: S. Pol, G. Everson, R. Ghalib, V. Rustgi, C. Martorell, H.A. Tatum, J. Lim, C. Hezode, U. Diva, P.D. Yin, R. Hindes
Journal: Journal of Hepatology (2010)
Use of Potassium Canrenoate to Suppress Ouabain-Induced Ventricular Arrhythmias in Dogs
Authors: BILLY K. YEH, PEI-KUN SUNG, ASIS K. SAHA
Journal: Circulation Research (1972)

Potassium canrenoate, a steroidal compound and a specific antagonist of aldosterone, had (1) a potent protective effect against ouabain-induced ventricular tachycardia in intact closed-chest dogs and (2) a potent antiarrhythmic effect in abolishing ventricular bigeminy and ventricular tachycardia due to ouabain intoxication in dogs. Conversion of ouabain-induced arrhythmias was usually associated with an improvement in atrioventricular conduction, but no significant alterations in blood pressure or myocardial contractility occurred. Equivalent doses of potassium chloride failed to delay the occurrence of or to abolish the ouabain-induced ventricular tachycardia. Therefore, the antiarrhythmic activity of potassium canrenoate does not seem to be related to the potassium ion in the molecule. Since the compound combines both antiarrhythmic and diuretic activity, potassium canrenoate may be a valuable clinical agent for patients on digitalis therapy.
Abstract 3111: Contribution of Improved Cardiorespiratory Functions to Increased Pain-Free and Maximal Walking Distance in Patients with Claudication Following Arm Ergometer or Treadmill Exercise Training
Authors: Ulf G Bronas, Diane Treat-Jacobson, Arthur S Leon
Journal: Circulation (2007)

Introduction: We previously reported that arm ergometer exercise training improves walking distance in patients with claudication similar to treadmill exercise training through unknown mechanisms. This is the first study to investigate the effects of 12 weeks of arm ergometer or treadmill training on cardiorespiratory functions during treadmill exercise testing in patients with claudication, as compared to a usual care control group. Hypothesis: Both arm ergometer and treadmill training will significantly improve cardiorespiratory functions, which will contribute to improvement in both pain-free walking distance (PFWD) and maximal walking distance (MWD). Methods: Participants (21m, 7f, mean age 65.6 yrs, 86 % smoke hx., 27% diabetes) with claudication were randomly assigned to supervised exercise training [arm ergometry (n=10) or treadmill (n=10) ] for 12 weeks, 3h/week, or to a usual care control group (n=8). Double product at stage 1 and at MWD, anaerobic threshold, and VO 2 at onset of claudication pain and VO 2 peak were assessed during a symptom-limited, graded treadmill exercise test. Changes in these functions from baseline were analyzed between groups via ANCOVA and associations between variables were determined by Pearson’s partial correlations. Results: Groups did not differ in baseline demographic, medical or exercise variables. There were significant differences in response of cardiorespiratory variables to training in both exercise groups compared to the control group, but no statistical differences between exercise groups. Significant moderate correlations were found between changes in all cardiorespiratory variables and changes in PFWD or MWD (Table 1 ). Conclusion: Improvements in cardiorespiratory functions following arm ergometer or treadmill training were significantly associated with changes in PFWD and MWD, supporting systemic contributions to exercise training-related improvements seen in patients with claudication. Changes from Baseline in Submaximal and Maximal Cardiorespiratory Variables and Walking Improvement
Emigrated Neutrophils Regulate Ventricular Contractility via α <sub>4</sub> Integrin
Authors: B. Y. Poon, C. A. Ward, W. R. Giles, P. Kubes
Journal: Circulation Research (1999)

Abstract —We have previously shown that CD18 and α 4 integrin were important in the adherence of emigrated neutrophils to cardiac myocytes. Whether either of these molecules is important in myocyte dysfunction is unclear. In this study, we measured contractility as an index of myocyte function. Control contractility was compared with shortening response in myocytes exposed to neutrophils in the presence and absence of anti-CD18 or anti-α 4 antibodies. Control unloaded cell shortening, expressed as a percentage of resting cell length, measured 10.06±1.16% (n=10) at 5 minutes. Circulating neutrophils caused a 35% reduction in cell shortening, an event prevented by anti-CD18, but not by anti-α 4 antibody. When emigrated neutrophils were added to the myocytes, a profound reduction (50%) in unloaded cell shortening was noted. A significant increase in CD18 and α 4 integrin was found on emigrated neutrophils. Addition of anti-CD18 antibody did not protect the myocyte from the emigrated neutrophils, whereas the addition of an anti-α 4 antibody significantly reduced neutrophil-induced cell shortening, despite some neutrophils still adhering to the myocytes. Furthermore, emigrated neutrophils were able to cause myocytes to go into contracture within 5 minutes in the presence of neutrophils with or without anti-CD18 antibody. In addition to the impairment in unloaded cell shortening, at later times (10 minutes), neutrophils also caused a 40% reduction in the rate of contraction and relaxation. The addition of either anti-CD18 or anti-α 4 antibody protected the myocytes from these changes. The data suggest that immunosuppression of CD18 on emigrated neutrophils was only partially effective in reducing myocyte dysfunction. In contrast, immunosuppression of the α 4 integrin alone was sufficient to dramatically reduce all parameters of cell dysfunction measured in this study.
Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison
Authors: Christopher P Cannon, Sean P Curtis, Garret A FitzGerald, Henry Krum, Amarjot Kaur, James A Bolognese, Alise S Reicin, Claire Bombardier, Michael E Weinblatt, Désirée van der Heijde, Erland Erdmann, Loren Laine
Journal: The Lancet (2006)
Identifying the target NSCLC patient for maintenance therapy: an analysis from a placebo-controlled, phase III trial of maintenance pemetrexed (H3E-MC-JMEN)
Authors: C. Obasaju, L. Bowman, P. Wang, W. Shen, K.B. Winfree, E.N. Smyth, M.E. Boye, W. John, T. Brodowicz, C.P. Belani
Journal: Annals of Oncology (2013)

This was a post hoc analysis of patients with non-squamous histology from a phase III maintenance pemetrexed study in advanced non-small cell lung cancer (NSCLC).The six symptom items' [average symptom burden index (ASBI)] mean at baseline was calculated using the lung cancer symptom scale (LCSS). Low and high symptom burden (LSB, ASBI < 25; HSB, ASBI ≥ 25) and performance status (PS: 0, 1) subgroups were analyzed for treatment effect on progression-free survival (PFS) and overall survival (OS) using the Cox proportional hazard models adjusted for demographic/clinical factors.Significantly longer PFS and OS for pemetrexed versus placebo occurred in LSB patients [PFS: median 5.1 versus 2.4 months, hazard ratio (HR) 0.49, P < 0.0001; OS: median 17.5 versus 11.0 months, HR 0.63, P = 0.0012] and PS 0 patients (PFS: median 5.5 versus 1.7 months, HR 0.36, P < 0.0001; OS: median 17.7 versus 10.3 months, HR 0.54, P = 0.0019). Significantly longer PFS, but not OS, occurred in HSB patients (median 3.7 versus 2.8 months, HR 0.50, P = 0.0033) and PS 1 patients (median 4.4 versus 2.8 months, HR 0.60, P = 0.0002).ASBI and PS are associated with survival for non-squamous NSCLC patients, suggesting that maintenance pemetrexed is useful for LSB or PS 0 patients following induction.
Long-term effects of nebulised salbutamol
Authors: P. D Phelan
Journal: Thorax (1981)

Late sequelae of chest injurySir,-The paper on this subject in your March issue (Thorax 1981;36:204-7) is of considerable interest but it a pity that the authors do not say anything about the relationship between symptoms and litigation.Though they found none between symptoms and duration of follow-up, it is important to know whether symptoms differed in those with settled and unsettled claims for compensation.I hope this information will be included in their next report.
TRPA1 and Sympathetic Activation Contribute to Increased Risk of Triggered Cardiac Arrhythmias in Hypertensive Rats Exposed to Diesel Exhaust
Authors: Mehdi S. Hazari, Najwa Haykal-Coates, Darrell W. Winsett, Q. Todd Krantz, Charly King, Daniel L. Costa, Aimen K. Farraj
Journal: Environmental Health Perspectives (2011)

Background: Diesel exhaust (DE), which is emitted from on- and off-road sources, is a complex mixture of toxic gaseous and particulate components that leads to triggered adverse cardiovascular effects such as arrhythmias.Objective: We hypothesized that increased risk of triggered arrhythmias 1 day after DE exposure is mediated by airway sensory nerves bearing transient receptor potential (TRP) channels [e.g., transient receptor potential cation channel, member A1 (TRPA1)] that, when activated by noxious chemicals, can cause a centrally mediated autonomic imbalance and heightened risk of arrhythmia.Methods: Spontaneously hypertensive rats implanted with radiotelemeters were whole-body exposed to either 500 μg/m3 (high) or 150 μg/m3 (low) whole DE (wDE) or filtered DE (fDE), or to filtered air (controls), for 4 hr. Arrhythmogenesis was assessed 24 hr later by continuous intravenous infusion of aconitine, an arrhythmogenic drug, while heart rate (HR) and electrocardiogram (ECG) were monitored.Results: Rats exposed to wDE or fDE had slightly higher HRs and increased low-frequency:high-frequency ratios (sympathetic modulation) than did controls; ECG showed prolonged ventricular depolarization and shortened repolarization periods. Rats exposed to wDE developed arrhythmia at lower doses of aconitine than did controls; the dose was even lower in rats exposed to fDE. Pretreatment of low wDE–exposed rats with a TRPA1 antagonist or sympathetic blockade prevented the heightened sensitivity to arrhythmia.Conclusions: These findings suggest that a single exposure to DE increases the sensitivity of the heart to triggered arrhythmias. The gaseous components appear to play an important role in the proarrhythmic response, which may be mediated by activation of TRPA1, and subsequent sympathetic modulation. As such, toxic inhalants may partly exhibit their toxicity by lowering the threshold for secondary triggers, complicating assessment of their risk.
Some Characteristics of Transmembrane Potentials of AV Nodal Cells during Propagation of Premature Beats
Authors: CARLOS MENDEZ, GORDON K. MOE
Journal: Circulation Research (1966)

Transmembrane potentials of AV nodal cells in isolated rabbit hearts were recorded during propagation of premature responses. With selected patterns of stimulation it was possible to obtain conduction block at different levels inside the AV node. When block occurred, action potentials recorded just proximal to the sites of block were brief. When propagation was barely successful, action potentials obtained from the same cells were prolonged and showed a hump in the repolarizing limb. Assuming that the AV node behaves as a functional syncytium, these phenomena can be explained as follows. (1) When conduction block occurs, local circuits established between active and inactive regions provide repolarizing current to the distal active region. This current will shorten the action potential of such cells. (2) When propagation is barely successful, the impulse may stop and resume its travel after a delay. While the impulse is arrested, repolarizing current will tend to shorten the action potential of the active region, but when propagation starts again, the newly excited tissue will provide depolarizing current to the previously active region, causing a delay in repolarization. Parallel changes in the refractory phase were also demonstrated.
Human Rhinovirus Species C Infection in Young Children with Acute Wheeze Is Associated with Increased Acute Respiratory Hospital Admissions
Authors: Desmond W. Cox, Joelene Bizzintino, Giovanni Ferrari, Siew Kim Khoo, Guicheng Zhang, Siobhan Whelan, Wai Ming Lee, Yury A. Bochkov, Gary C. Geelhoed, Jack Goldblatt, James E. Gern, Ingrid A. Laing, Peter N. Le Souëf
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Human rhinovirus species C (HRV-C) is the most common cause of acute wheezing exacerbations in young children presenting to hospital, but its impact on subsequent respiratory illnesses has not been defined.
Donepezil for Cancer Fatigue: A Double-Blind, Randomized, Placebo-Controlled Trial
Authors: Eduardo Bruera, Badi El Osta, Vicente Valero, Larry C. Driver, Be-Lian Pei, Loren Shen, Valerie A. Poulter, J. Lynn Palmer
Journal: Journal of Clinical Oncology (2007)

To evaluate the effectiveness of donepezil compared with placebo in cancer patients with fatigue as measured by the Functional Assessment for Chronic Illness Therapy-Fatigue (FACIT-F).Patients with fatigue score >or= 4 on a scale of 0 to 10 (0 = no fatigue, 10 = worst possible fatigue) for more than 1 week were included. Patients were randomly assigned to receive donepezil 5 mg or placebo orally every morning for 7 days. A research nurse contacted the patients by telephone daily to assess toxicity and fatigue level. All patients were offered open-label donepezil during the second week. FACIT-F and/or the Edmonton Symptom Assessment System (ESAS) were assessed at baseline, and days 8, 11, and 15. The FACIT-F fatigue subscale score on day 8 was considered the primary end point.Of 142 patients randomly assigned to treatment, 47 patients in the donepezil group and 56 in the placebo group were assessable for final analysis. Fatigue intensity improved significantly on day 8 in both donepezil and placebo groups. However, there was no significant difference in fatigue improvement by FACIT-F (P = .57) or ESAS (P = .18) between groups. In the open-label phase, fatigue intensity continued to be low as compared with baseline. No significant toxicities were observed.Donepezil was not significantly superior to placebo in the treatment of cancer-related fatigue.
Targeted enrichment beyond the consensus coding DNA sequence exome reveals exons with higher variant densities
Authors: Matthew N Bainbridge, Min Wang, Yuanqing Wu, Irene Newsham, Donna M Muzny, John L Jefferies, Thomas J Albert, Daniel L Burgess, Richard A Gibbs
Journal: Genome biology (2011)

Abstract Background Enrichment of loci by DNA hybridization-capture, followed by high-throughput sequencing, is an important tool in modern genetics. Currently, the most common targets for enrichment are the protein coding exons represented by the consensus coding DNA sequence (CCDS). The CCDS, however, excludes many actual or computationally predicted coding exons present in other databases, such as RefSeq and Vega, and non-coding functional elements such as untranslated and regulatory regions. The number of variants per base pair (variant density) and our ability to interrogate regions outside of the CCDS regions is consequently less well understood. Results We examine capture sequence data from outside of the CCDS regions and find that extremes of GC content that are present in different subregions of the genome can reduce the local capture sequence coverage to less than 50% relative to the CCDS. This effect is due to biases inherent in both the Illumina and SOLiD sequencing platforms that are exacerbated by the capture process. Interestingly, for two subregion types, microRNA and predicted exons, the capture process yields higher than expected coverage when compared to whole genome sequencing. Lastly, we examine the variation present in non-CCDS regions and find that predicted exons, as well as exonic regions specific to RefSeq and Vega, show much higher variant densities than the CCDS. Conclusions We show that regions outside of the CCDS perform less efficiently in capture sequence experiments. Further, we show that the variant density in computationally predicted exons is more than 2.5-times higher than that observed in the CCDS.
THE EFFECTS OF INTRASPINAL INJECTION OF MAGNESIUM SALTS UPON TETANUS
Authors: S. J. Meltzer, John Auer
Journal: The Journal of Experimental Medicine (1906)

Intraspinal injections of magnesium sulphate, in doses which do not affect the respiratory centre or other vital function, are capable of abolishing completely all clonic convulsions and tonic contractions in cases of human tetanus, and experimental tetanus in monkeys. The relaxing effects of the injections may last twenty-four hours or longer. In experimental tetanus in monkeys early intraspinal injections of magnesium salts are capable of retarding the progress and development of the tetanic symptoms.
<i>BRAF</i> Mutation Testing of Thyroid Fine-Needle Aspiration Biopsy Specimens for Preoperative Risk Stratification in Papillary Thyroid Cancer
Authors: Mingzhao Xing, Douglas Clark, Haixia Guan, Meiju Ji, Alan Dackiw, Kathryn A. Carson, Matthew Kim, Anthony Tufaro, Paul Ladenson, Martha Zeiger, Ralph Tufano
Journal: Journal of Clinical Oncology (2009)

This study investigated the utility of BRAF mutation testing of thyroid fine-needle aspiration biopsy (FNAB) specimens for preoperative risk stratification in papillary thyroid cancer (PTC).We assessed the T1799A BRAF mutation status in thyroid FNAB specimens obtained from 190 patients before thyroidectomy for PTC and its association with clinicopathologic characteristics of the tumor revealed postoperatively.We observed a significant association of BRAF mutation in preoperative FNAB specimens with poorer clinicopathologic outcomes of PTC. In comparison with the wild-type allele, BRAF mutation strongly predicted extrathyroidal extension (23% v 11%; P = .039), thyroid capsular invasion (29% v 16%; P = .045), and lymph node metastasis (38% v 18%; P = .002). During a median follow-up of 3 years (range, 0.6 to 10 years), PTC persistence/recurrence was seen in 36% of BRAF mutation-positive patients versus 12% of BRAF mutation-negative patients, with an odds ratio of 4.16 (95% CI, 1.70 to 10.17; P = .002). The positive and negative predictive values for preoperative FNAB-detected BRAF mutation to predict PTC persistence/recurrence were 36% and 88% for overall PTC and 34% and 92% for conventional PTC, respectively.Preoperative BRAF mutation testing of FNAB specimens provides a novel tool to preoperatively identify PTC patients at higher risk for extensive disease (extrathyroidal extension and lymph node metastases) and those who are more likely to manifest disease persistence/recurrence. BRAF mutation, as a powerful risk prognostic marker, may therefore be useful in appropriately tailoring the initial surgical extent for patients with PTC.