tbuckley/cabot-search huggingface dataset:
Abstract P414: Omega-3 Fatty Acids Modify the Genetic Risk of Early Onset Acute Coronary Syndrome
Authors: Sylvie S Leung Yinko, James C Engert, George Thanassoulis`, Ken D Stark, Meytal Avgil Tsadok, Louise Pilote
Journal: Circulation (2014)

Background: Recent gene-environment interaction studies suggest that diet may influence an individual’s genetic predisposition to cardiovascular risk. We tested the hypothesis that omega-3 fatty acid intake may influence the risk for acute coronary syndrome (ACS) conferred by genetic polymorphisms among patients with premature ACS. Methods: Our study population consisted of 706 patients of white European descent enrolled in GENESIS PRAXY, a multicentre prospective cohort study of patients aged 18 to 55 years hospitalized with ACS. We used a case-only design to investigate gene-environment interactions between the omega-3 index (a validated biomarker of omega-3 fatty acid intake) and 30 single nucleotide polymorphisms (SNPs) that have been robustly associated with ACS. We used logistic regression to study the associations between each SNP and the omega-3 index. Interaction was also assessed between the omega-3 index and a genetic risk score generated from the 30 SNPs as a simple unweighted count of the risk alleles for each SNP. All the SNPs used in the genetic risk score were uncorrelated (r2 &lt;0.3). We further adjusted all models for age and sex. Results: The median age of our population was 49 years and 72.1% were male. Median omega-3 index was 3.35% (interquartile range 2.81-4.07%). None of the SNPs deviated from Hardy-Weinberg equilibrium. A synergistic multiplicative interaction for increased ACS risk was found between carriers of chromosome 9p21 variant rs4977574 and low omega-3 index (OR 1.57, 95% CI 1.07-2.32, p=0.02), but did not reach significance after correction for multiple testing. Similar results were obtained in the adjusted model (OR 1.55, 95% CI 1.05-2.29, p=0.03). We did not observe interaction between the genetic risk score and the omega-3 index. Conclusions: In conclusion, our results suggest that omega-3 fatty acid intake may modify the genetic risk conferred by chromosome 9p21 variation among ACS patients but require independent replication in other cohorts. Further validation research is also warranted to examine whether this interaction occurs in other ethnic groups.
Apoptosis of peripheral blood lymphocytes in different periods of asthma
Authors: Zhanna Antanovich, Vladimir Tsarev, Nataliya Goncharova
Journal: European Respiratory Journal (2011)

Background:  Resistance of lymphocytes to apoptosis can cause decrease of these cells elimination from respiratory ways and play a key role in persistence of inflammation in asthma.   Objective:  The aim of this study was to reveal the disturbances of blood lymphocytes apoptosis in different periods of asthma.   Methods:  25 steroid naive asthmatic adults with asthma exacerbation and 25 with asthma remission were randomly selected and 20 matched control subjects were included. All were submitted to detailed clinical history and examination, pulmonary function testing. Peripheral blood lymphocytes (PBLs) were stimulated by phytoagglutinin (PHA) and cultured for 72 hours. Apoptosis of PBLs was determined by flow cytometry by evaluating of Annexin V expression for detection of early apoptotic cells (Annexin V positive-PI negative).   Results:  Subjects with asthma exacerbation had significantly lower values of early apoptotic cells in blood than subjects with asthma remission (20,29±1,69% vs 41,65±2,38%; p 0,05).   Conclusion:  The value of early apoptotic cells in 72 hours cultures of stimulated by PHA lymphocytes is a sensitive marker for asthma exacerbation and remission and can be predictor for asthma exacerbation.
Abstract 19251: Glucose-6-Phosphate Dehydrogenase Regulates Myocardin and Phenotype of Arterial Smooth Muscle Cells in Metabolic Syndrome Swine and Humans
Authors: Vidhi Dhagia, Mouhamad Alloosh, Michael Sturek, Rakhee Gupte, Sachin A Gupte
Journal: Circulation (2014)

We discovered that activity of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme in the pentose phosphate pathway, is increased and expression of myocardin, the key co-transcription factor that regulates the vascular smooth muscle cell (VSMC) phenotype and plasticity, is decreased in the arteries of metabolic sydnrome (MetS) pigs and humans. Therefore, in this study, we investigated whether there is any correlation between reprograming of glucose metabolism/increase of G6PD activity and decrease of myocardin expression in arteries of MetS pigs. We measured G6PD activity and expression of myocardin and myocardin-dependent contractile protein genes in coronary and carotid arteries of lean and MetS Ossabaw miniature pigs. We found a negative correlation (R2=0.89; P<0.05; n=6) between G6PD activity and myocardin expression in coronary arteries of lean pigs. Furthermore, we found in MetS vs. Lean pigs that G6PD activity increased by 2-fold (Lean: 1.25±0.47, n=13; MetS: 3.54±0.89, n=8; P<0.05) ...
Interferon alfa for treatment of pediatric chronic hepatitis B: A randomized controlled multicenter trial.
Authors: Etienne Sokal, H Conjeevaram, EA Roberts, F. Alvarez, EM Bern, P Goyens, P Rosenthal, A Lachaux, M Shelton, J Sarles, J Albrecht, J Hoofnagle, C LeTallec, F Bury, D Debray, J Molleston, A Dabadie, RA Schreiber, RJ Zwiener, A Deprettere, G. Veereman, D Kleiner, C. Cornu
Journal: Hepatology (1997)
Can the Lung Cancer Pie Be Divided into Angiogenic Slices?
Authors: Tina Cascone, John V. Heymach
Journal: Clinical Cancer Research (2015)

Abstract There are no validated markers for predicting benefit from angiogenesis inhibitors or classifying tumors with distinct angiogenic phenotypes. In patients with non–small cell lung cancer treated with bevacizumab and erlotinib, Franzini and colleagues find that angiogenesis- and hypoxia-associated gene expression signatures predict tumor response and/or clinical outcome, and may define distinct angiogenic patterns. Clin Cancer Res; 21(23); 5188–90. ©2015 AACR. See related article by Franzini et al., p. 5253
Abstract 14492: Effect of Acute Exercise on Statin Induced Muscle Damage in Exercise Trained Subjects.
Authors: Geetha Swamy Iyah, Afrooz Ardestani, Beth Parker, Shishir Mathur, Vamsi Pavuluri, Donna Polk, Paul Thompson
Journal: Circulation (2011)

Objectives: Statins magnify the increase in serum creatine kinase (CK) produced by eccentric exercise in exercise-untrained subjects. The present study compared increases in CK after 4.75 mile road...
Treatment with inhaled corticosteroids (ICS) and long acting b2-agonists (LABA) combination in patients with COPD: Possible way of optimization
Authors: Tetyana Pertseva, Kateryna Gashynova
Journal: European Respiratory Journal (2011)

Respiratory muscles dysfunction in patients with COPD could affect the inhalation technique and be one of the causes of ICS and brochodilator's inefficacy.

Aim of study: To evaluate efficacy of Budesonide/Formoterol combination in dry powder inhaler (Symbicort, Astra Zeneca) in patients with COPD (stage III) with signs of respiratory muscles dysfunction.

Study population and Methods: 20 patients with COPD III (17 men, mean age 58.9±6.3 yrs), who regularly treated by high doses of any ICS and bronchodilators no less than three month made the study sample. All patients were current smokers and had signs of respiratory muscles dysfunction (PImax ≤60 kPa).

At baseline all patient withdrawn from their COPD therapy and were prescribed Budesonide/Formoterol combination 320/9 mcg BID.

Pulmonary function tests (FEV1, MMLV), PImax, 6MWD and plasma C- reactive protein were evaluated before and 12 months after beginning of the study.

Results: Results are present in Table 1.

View this table:



Conclusions: Long-term prescription of Budesonide/Formoterol combination in dry powder inhaler (Symbicort, Astra Zeneca) in COPD patients with signs of respiratory muscles dysfunction significantly increase their MMVL, exercises capacity and reduce respiratory muscles fatigue and systemic inflammation.
Practicing empirical anti-tuberculosis treatment (ATT) in suspected spinal tuberculosis (STB): Follow up of 33 cases from Sri Lanka, a limited resource setting with an intermediate disease burden
Authors: Duminda Yasaratne, Dushantha Madegedara, Keerthi Weerawardhana, Prasanna Wijerathne, Kulathunga Nishantha, Samadara Nakandala, Neranjan Dissanayake, Chathura Wirasinghe
Journal: European Respiratory Journal (2011)

Background: Some patients with clinically suspected STB are given empirical ATT under specialist supervision, without histological or microbiological confirmation of disease, due to lack of resources.

Aim: To assess the outcome following empirical ATT in a cohort with a clinical diagnosis of STB.

Methodology: We followed up 33 patients diagnosed with STB based on history, negative blood culture, spinal CT and/or MR imaging and supported by tuberculin test and inflammatory markers. None had microbiological or histological confirmation. All were given standard category I ATT, with prolonged regimen for neurologically complicated disease.

Results: CT/MRI showed end plate destruction/sclerosis and/or evidence of discitis in 28 patients, with paraspinal and psoas abscesses in some. In the remaining five, imaging findings were atypical. One patient died and another with body and pedicle destruction was found to have metastatic spinal disease. 22 completed ATT, while 9 are still on treatment, completing minimum of six months. All 31 patients followed up, including 4 with atypical imaging features, had symptomatic improvement with ESR normalizing in 90% and weight gain in 77%. Serial spinal X-rays did not show worsening in any. None had ATT related major adverse effects. Six with neurological deficits had completed 12 months ATT, where the recovery was full in 4 and partial in 2.

Conclusion: Imaging based diagnosis of STB and empirical ATT with close supervision appears to be safe and effective, in a setting with high degree of clinical suspicion, low drug resistance and limited resources.
Prevalence of Penicillin-Resistant Streptococcus pneumoniae—Connecticut, 1992-1993
Authors: E. Hatheway Simpson
Journal: JAMA (1994)

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Abstract 1717: Impact of a 600-mg Loading Dose of Clopidogrel on 30-Day Outcome in Unselected Patients Undergoing Percutaneous Coronary Intervention
Authors: Laurent Bonello, Gilles Lemesle, Axel de Labriolle, Probal Roy, Daniel H Steinberg, Tina Pinto Slottow, Zhenyi Xue, Rebecca Torguson, Kimberly Kaneshige, William Suddath, Kenneth Kent, Lowell Satler, Augusto Pichard, Ron Waksman
Journal: Circulation (2008)

Background: Based on biological studies of platelet reactivity (PR), the recent ACC/AHA guidelines recommend a 600-mg loading dose (LD) of clopidogrel in patients undergoing percutaneous coronary intervention (PCI). However, there is lack of studies addressing the clinical impact of such a LD of clopidogrel. Objective: We aimed to compare the clinical efficacy and safety of a 600-mg LD of clopidogrel compared to a 300-mg LD in an unselected cohort of patients undergoing PCI. Methods: A cohort of 4105 unselected patients undergoing PCI in our institution was included in the study and divided according to the LD used: the high LD group (600mg) included 3146 patients and the low LD (300mg) group included 959. The primary endpoint was the rate of major adverse cardiovascular events (MACE) at 1 month. Results: Patients in lthe ow LD group more often had diabetes mellitus and a history of myocardial infarction (36.8 vs 31.9%; p = 0.01). Left ventricular ejection fraction was similar (0.49 ± 0.14 vs 0.48 ± 0.14; p = 0.25). Angiographic and procedural characteristics were identical between the 2 groups. Patients in the high LD group had fewer MACE after 1 month (2.9 vs 5.2%; p &lt; 0.001). In multivariate analysis, a 600-mg LD of clopidogrel was significantly associated with MACE at 1-month follow-up, with an odds ratio of 0.62 (95% CI 0.41– 0.95; p = 0.03). Conclusions: A 600-mg LD was associated with a significant decrease in the rate of post PCI-MACE at 1 month without any increase in bleeding complications. The results of our study therefore support the current guideline of a 600-mg LD of clopidogrel in patients undergoing PCI.
Noninvasive ventilation (NIV) in do-not-intubate (DNI) patients in a chronic disease hospital
Authors: Eva Tabernero, Pilar Gil, Ramon Alkiza, Anibal Hernandez, Javier Garros, Ramon Herreria, Juan Luis Artola, Javier Villuela
Journal: European Respiratory Journal (2014)

Elderly patients with polypathology and DNI orders frequently present with acute respiratory failure. There are data supporting the effectiveness of NIV in this context. Our center, a chronic disease hospital, developed in 2010 an integrated care pathway for NIV in acute respiratory failure in the emergency room and wards

AIMS : Assess the outcome of NIV in patients with acute respiratory failure with a DNI order in a subacute care hospital

METHODS: Observational, one year-follow up study. Variables recorded were: demographics, clinical and functional data, performance of daily life activities, dementia, arterial blood gases, readmisisions and 1-year mortality

RESULTS: We included 102 patientes. mean age 81+/-7, with a Charlson Index 3,7+/-1, 22% were institutionalized. The overall mortality during the admission was 33% (n=34). 14 patients (13%) were ventilated outside the protocol indications. In this group mortality was 71%, (p>0.05). One year survival rate was 47%. This survival rate was statistically higher in patients with obesity hypoventilation sindrome (OHS), NIV at discharge and Barthel> 50

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Conclusions 

NIV is an useful technique in an elderly population with a therapeutic ceiling. Despite their disease severity and comorbidity, acceptable survival rates are achieved. A correct case selection is needed. OHS and those with Barthel index >50 have better prognosis.
Abstract #5552: BSI-201 enhances the activity of multiple classes of cytotoxic agents and irradiation in triple negative breast cancer
Authors: Valeria Ossovskaya, Lingyun Li, Eugenia Broude, Chang-Uk Lim, Igor Roninson, Charles Bradley, Barry Sherman
Journal: Cancer Research (2009)

Introduction:  Triple negative breast cancer (TNBC) is a distinct and aggressive subtype of breast cancer that accounts for 15-20% of all breast cancers. Due to lack of expression of estrogen and progesterone receptors and lack of overexpression of Her-2, no effective targeted regimens exist for this cancer subtype. TNBC is attributed to accumulation of defects in homologous recombination-dependent DNA double-strand break repair pathways, including BRCA1/2. Thus, TNBC represents an attractive target for therapeutic intervention directed against DNA repair. Poly (ADP-ribose) polymerase-1 (PARP1) is a key DNA-binding enzyme that controls DNA repair, transcription, mitosis, and apoptosis. Importantly, PARP1 is significantly upregulated in a number of primary malignancies, including TNBC. Here we report the activity of BSI-201, a potent PARP1 inhibitor, in combination with chemotherapy or gamma-irradiation in metastatic TNBC.  Methods :  In vitro  activity of single dose BSI-201 was tested in combination with carboplatin, gemcitabine, irinotecan, or gamma-irradiation in MDA-MB-468 metastatic TNBC cells in flow cytometric analysis of the cell cycle. Percentages of viable cells in G1, S, or G2/M were determined by ModFit software. Percent cells in apoptosis were determined by TUNEL (TdT-mediated dUTP Nick-End Labeling) assay.  In vivo  activity of BSI-201 was assessed in tumor xenografts initiated by subcutaneous injection of MDA-MB-231 metastatic TNBC cells into female athymic nude mice. BSI-201 (50 mg/kg; ip) was delivered twice weekly; gemcitabine (15 mg/kg; ip) and carboplatin (10 mg/kg; ip) were administered every 3 days and once weekly, respectively, for 3 weeks.  Results : BSI-201 potentiated the activity of carboplatin in MDA-MB-468 cells, resulting in S and G2/M cell cycle arrest. BSI-201 facilitated gemcitabine- and irinotecan-induced S and G2/M arrest, followed by apoptosis. Combination of BSI-201 with gamma-irradiation also resulted in profound G2/M cell cycle arrest. BSI-201 plus gemcitabine/carboplatin demonstrated a robust tumor response against MDA-MB-231 xenografts in nude mice, with 4 partial responses (PR), 2 complete responses (CR), and 1 tumor-free survivor (TFS), compared with only 4 PR in the group treated only with gemcitabine/carboplatin. BSI-201 was well tolerated, with no reported toxicities.  Conclusions:  BSI-201 is a promising new targeted therapeutic agent that is well tolerated and has potent activity  in vitro  and  in vivo  against metastatic TNBC when used in combination with DNA damaging agents, such as carboplatin, gemcitabine, irrinotecan, or gamma-irradiation.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5552.
Antibiotic use among Dutch pregnant woman and the development of toddler asthma: The influence of confounding
Authors: Bianca Mulder, Koen Pouwels, Catherina Schuiling-Veninga, Jens Bos, Tjalling de Vries, Susan Jick, Eelko Hak
Journal: European Respiratory Journal (2014)

Background: Recent studies have reported increased childhood asthma risks after prenatal exposure to antibiotics. Associations could have been influenced by unmeasured confounders.

Objectives: To assess the association between antibiotic use during pregnancy and the development of toddler asthma with a confounding minimizing crossover design. Second, we assessed the influence of time-invariant confounding by comparing results with a case-control design.

Methods: Data was obducted from the prescription database IADB.nl. We conducted a crossover study in which 1,228 children with asthma were compared to their own siblings without asthma, and a traditional matched case-control study. Maternal exposure was defined as ≥1 day of supply of systemic antibiotics during pregnancy. Toddler asthma was defined as having received ≥3 prescriptions for asthma medication within a year before the fifth birthday. Conditional logistic regression was used to estimate crude and adjusted odds ratios(aOR).

Results: The crossover analysis only showed an increase in the toddler's asthma risk if antibiotics were used in the third trimester of pregnancy (aOR 1.37(95%CI 1.02-1.83)). Results were similar in the case-control study after exposure in the third trimester (aOR 1.40(95%CI 1.15-1.47)). In addition, use of antibiotics, independent of trimester of pregnancy, was associated with an aOR of 1.46 (95%CI 1.33-1.58) in the case-control study.

Conclusions: Prenatal exposure to antibiotics in the third trimester of pregnancy is associated with a small increased risk of toddler asthma. This association did not appear to be influenced by time-invariant confounders such as genetic predisposition.
Low-Molecular-Weight Heparin for Women With Unexplained Recurrent Pregnancy Loss
Authors: Ekkehard Schleussner, Gabriele Kamin, Gregor Seliger, Nina Rogenhofer, Susanne Ebner, Bettina Toth, Michael Schenk, Melanie Henes, Michael K. Bohlmann, Thorsten Fischer, Oana Brosteanu, Rupert Bauersachs, David Petroff
Journal: Annals of Internal Medicine (2015)

A daily injection of low-molecular-weight heparin (LMWH) is often prescribed to women with unexplained recurrent pregnancy loss (RPL), although evidence suggesting a benefit is questionable.To determine whether LMWH increases ongoing pregnancy and live-birth rates in women with unexplained RPL.Controlled, multicenter trial with randomization using minimization conducted from 2006 to 2013. (ClinicalTrials.gov: NCT00400387).14 university hospitals and perinatal care centers in Germany and Austria.449 women with at least 2 consecutive early miscarriages or 1 late miscarriage were included during 5 to 8 weeks' gestation after a viable pregnancy was confirmed by ultrasonography.Women in the control group received multivitamin pills, and the intervention group received vitamins and 5000 IU of dalteparin-sodium for up to 24 weeks' gestation.Primary outcome was ongoing pregnancy at 24 weeks' gestation. Secondary outcomes included the live-birth rate and late pregnancy complications.At 24 weeks' gestation, 191 of 220 pregnancies (86.8%) and 188 of 214 pregnancies (87.9%) were intact in the intervention and control groups, respectively (absolute difference, -1.1 percentage points [95% CI, -7.4 to 5.3 percentage points]). The live-birth rates were 86.0% (185 of 215 women) and 86.7% (183 of 211 women) in the intervention and control groups, respectively (absolute difference, -0.7 percentage point [CI, -7.3 to 5.9 percentage points]). There were 3 intrauterine fetal deaths (1 woman had used LMWH); 9 cases of preeclampsia or the hemolysis, elevated liver enzyme level, and low platelet count (HELLP) syndrome (3 women had used LMWH); and 11 cases of intrauterine growth restriction or placental insufficiency (5 women had used LMWH).Placebo injections were not used, and neither trial staff nor patients were blinded.Daily LMWH injections do not increase ongoing pregnancy or live-birth rates in women with unexplained RPL. Given the burden of the injections, they are not recommended for preventing miscarriage.Pfizer Pharma.