tbuckley/cabot-search huggingface dataset:
Prevalence and clinical correlates of bronchoreversibility in severe emphysema
Authors: M. K. Han, R. Wise, J. Mumford, F. Sciurba, G. J. Criner, J. L. Curtis, S. Murray, A. Sternberg, G. Weinman, E. Kazerooni, A. P. Fishman, B. Make, E. A. Hoffman, Z. Mosenifar, F. J. Martinez
Journal: European Respiratory Journal (2009)

Chronic obstructive pulmonary disease (COPD) exhibits airflow obstruction that is not fully reversible. The importance of bronchoreversibility remains controversial. We hypothesised that an emphysematous phenotype of COPD would be associated with decreased bronchoreversibility. 544 patients randomised to the medical arm of the National Emphysema Treatment Trial formed the study group. Participants underwent multiple measurements of bronchoreversibility on a mean of four sessions over 1.91 yrs. They were also characterised by measures of symptoms, quality of life and quantitative measures of emphysema by computed tomography. Mean baseline forced expiratory volume in 1 s (FEV 1 ) in this patient population is 24% predicted. 22.2% of patients demonstrated bronchoreversibility on one or more occasions using American Thoracic Society/European Respiratory Society criteria. Few patients (0.37%) had bronchoreversibility on all completed tests. Patients who demonstrated bronchoreversibility were more likely to be male, and have better lung function and less emphysema. 64% of patients demonstrated large (≥400 mL) changes in forced vital capacity (FVC). In a severe emphysema population, bronchoreversibility as defined by change in FEV 1 is infrequent, varies over time, and is more common in males and those with less severe emphysema. Improvements in FVC, however, were demonstrated in the majority of patients.
Estrogen Receptor α Inhibits p53-Mediated Transcriptional Repression: Implications for the Regulation of Apoptosis
Authors: Aejaz Sayeed, Santhi D. Konduri, Wensheng Liu, Sanjay Bansal, Fengzhi Li, Gokul M. Das
Journal: Cancer Research (2007)

Abstract Estrogen receptor α (ERα) and tumor suppressor protein p53 exert opposing effects on cellular proliferation. As a transcriptional regulator, p53 is capable of activating or repressing various target genes. We have previously reported that ERα binds directly to p53, leading to down-regulation of transcriptional activation by p53. In addition to transcriptional activation, transcriptional repression of a subset of target genes by p53 plays important roles in diverse biological processes, such as apoptosis. Here, we report that ERα inhibits p53-mediated transcriptional repression. Chromatin immunoprecipitation assays reveal that ERα interacts in vivo with p53 bound to promoters of Survivin and multidrug resistance gene 1, both targets for transcriptional repression by p53. ERα binding to p53 leads to inhibition of p53-mediated transcriptional regulation of these genes in human cancer cells. Transcriptional derepression of Survivin by ERα is dependent on the p53-binding site on the Survivin promoter, consistent with our observation that p53 is necessary for ERα to access the promoters. Importantly, mutagenic conversion of this site to an activation element enabled ERα to repress p53-mediated transcriptional activation. Further, RNA interference–mediated knockdown of ERα resulted in reduced Survivin expression and enhanced the propensity of MCF-7 cells to undergo apoptosis in response to staurosporine treatment, an effect that was blocked by exogenous expression of Survivin. These results unravel a novel mechanism by which ERα opposes p53-mediated apoptosis in breast cancer cells. The findings could have translational implications in developing new therapeutic and prevention strategies against breast cancer. [Cancer Res 2007;67(16):7746–55]
Long QT syndrome patients genetically linked to defective genes on chromosomes 11, 7 and 3 present differential response to changes in heart rate
Authors: Silvia G. Priori, Carlo Napolitano, Emanuela H. Locati, Francesco Cantù, Marco Stramba-Badiale, Mark T. Keating, Jeffrey A. Towbin, Thomas J. Colatsky, Ling Sing K. Chen, Peter J. Schwartz
Journal: Journal of the American College of Cardiology (1996)
Chronic Lung Disease, Polycythemia and Congestive Heart Failure
Authors: CEYLON S. LEWIS, ARTHUR J. SAMUELS, MERRILL C. DAINES, HANS H. HECHT
Journal: Circulation (1952)

The relationship of chronic lung disease, congestive heart failure and polycythemia has been examined in 32 subjects including "normal" and "abnormal" controls. The study revealed differences and similarities between cor pulmonale and other types of heart disease. The observations demonstrated a correlation between arterial oxygen tension, as calculated from oxygen content and oxygen capacity, and pulmonary artery pressure. Lowered renal clearance was present in all instances of congestive failure, irrespective of its etiology or of the resting level of cardiac output. It seemed from this preliminary study that bleeding a polycythemic subject with chronic lung disease uncovers a state of oxygen unsaturation that may reflect the conditions which originally led to the development of secondary polycythemia. The possible significance of "oxygen transport" and of altered blood fluidity on the mechanism of heart failure in chronic lung disease is discussed.
Single- Versus Multiple-Fraction Radiotherapy in Patients With Painful Bone Metastases: Cost-Utility Analysis Based on a Randomized Trial
Authors: Wilbert B van den Hout, Yvette M van der Linden, Elsbeth Steenland, Ruud G J Wiggenraad, Job Kievit, Hanneke de Haes, Jan Willem H Leer
Journal: JNCI Journal of the National Cancer Institute (2003)

Background: Radiotherapy is an effective palliative treatment for cancer patients with painful bone metastases. Although single- and multiple-fraction radiotherapy are thought to provide equal palliation, which treatment schedule provides better value for the money is unknown. We compared quality-adjusted life expectancy (the overall valuation of the health of the patients) and societal costs for patients receiving either single- or multiple-fraction radiotherapy. Methods: A societal cost–utility analysis was performed on a Dutch randomized, controlled trial of 1157 patients with painful bone metastases that compared pain responses and quality of life from a single-fraction treatment schedule of 8 Gy with a treatment schedule of six fractions of 4 Gy each. The societal values of life expectancies were assessed with the EuroQol classification system (EQ-5D) questionnaire. A subset of 166 patients also answered additional questionnaires to estimate nonradiotherapy and nonmedical costs. Statistical tests were two-sided. Results: Comparing the single- and multiple-fraction radiotherapy schedules, no differences were found in life expectancy (43.0 versus 40.4 weeks, P = .20) or quality-adjusted life expectancy (17.7 versus 16.0 weeks, P = .21). The estimated cost of radiotherapy, including retreatments and nonmedical costs, was statistically significantly lower for the single-fraction schedule than for the multiple-fraction schedule ($2438 versus $3311, difference = $873, 95% confidence interval [CI] on the difference = $449 to $1297; P<.001). The estimated difference in total societal costs was larger, also in favor of the single-fraction schedule, but it was not statistically significant ($4700 versus $6453, difference = $1753, 95% CI on the difference = –$99 to $3604; P = .06). For willingness-to-pay between $5000 and $40 000 per quality-adjusted life year, the single-fraction schedule was statistically significantly more cost-effective than the multiple-fraction schedule (P≤.05). Conclusions: Compared with multiple-fraction radiotherapy, single-fraction radiotherapy provides equal palliation and quality of life and has lower medical and societal costs, at least in The Netherlands. Therefore, single-fraction radiotherapy should be considered as the palliative treatment of choice for cancer patients with painful bone metastases.
A single-season prospective study of respiratory viral infections in lung transplant recipients
Authors: A. P. Milstone, L. M. Brumble, J. Barnes, W. Estes, J. E. Loyd, R. N. Pierson, S. Dummer
Journal: European Respiratory Journal (2006)

The frequency and complications of respiratory viral infections (RVI) were studied in 50 ambulatory lung transplant patients during a single winter season, using viral antigens, viral cultures and PCR of nasal washes or bronchoalveolar lavages. Patients' survival, episodes of acute rejection and occurrence of bronchiolitis obliterans (BO) or BO syndrome (BOS) were monitored for 1 yr after the study. Overall, 32 (64%) patients had 49 symptomatic episodes. Documented infections included eight due to respiratory syncytial virus (RSV), one due to parainfluenza virus (PIV) and 10 due to influenza (FLU). Four of the FLU infections were serological rises without symptoms. Overall, 17 (34%) patients had documented viral infection; four patients had lower respiratory involvement and two (one RSV, one PIV) were hospitalised for aerosolised ribavirin treatment. After 1 yr there were three (6%) deaths unrelated to RVI. BO or BOS had occurred in one (6%) out of 17 patients with and three (12%) out of 33 without RVI. Respiratory viruses infected one-third of ambulatory lung transplant recipients in a single season. In conclusion, respiratory viral infection was not associated with subsequent graft dysfunction. Larger prospective studies are required to better define the acute and long-term morbidity of these infections.
The Efficacy and Safety of Multivitamin and Mineral Supplement Use To Prevent Cancer and Chronic Disease in Adults: A Systematic Review for a National Institutes of Health State-of-the-Science Conference
Authors: Han-Yao Huang, Benjamin Caballero, Stephanie Chang, Anthony J. Alberg, Richard D. Semba, Christine R. Schneyer, Renee F. Wilson, Ting-Yuan Cheng, Jason Vassy, Gregory Prokopowicz, George J. Barnes, Eric B. Bass
Journal: Annals of Internal Medicine (2006)

Background: Multivitamin and mineral supplements are the most commonly used dietary supplements in the United States. Purpose: To synthesize studies on the efficacy and safety of multivitamin/mineral supplement use in primary prevention of cancer and chronic disease in the general population. Data Sources: English-language literature search of the MEDLINE, EMBASE, and Cochrane databases through February 2006 and hand-searching of pertinent journals and articles. Study Selection: Randomized, controlled trials in adults were reviewed to assess efficacy, and randomized, controlled trials and observational studies in adults or children were reviewed to assess safety. Data Extraction: Paired reviewers extracted data and independently assessed study quality. Data Synthesis: 12 articles from 5 randomized, controlled trials that assessed efficacy and 8 articles from 4 randomized, controlled trials and 3 case reports on adverse effects were identified. Study quality was rated fair for the studies on cancer, cardiovascular disease, cataracts, or age-related macular degeneration and poor for the studies on hypertension. In a poorly nourished Chinese population, combined supplementation with β-carotene, α-tocopherol, and selenium reduced the incidence of and mortality rate from gastric cancer and the overall mortality rate from cancer by 13% to 21%. In a French trial, combined supplementation with vitamin C, vitamin E, β-carotene, selenium, and zinc reduced the rate of cancer by 31% in men but not in women. Multivitamin and mineral supplements had no significant effect on cardiovascular disease or cataracts, except that combined β-carotene, selenium, α-tocopherol, retinol, and zinc supplementation reduced the mortality rate from stroke by 29% in the Linxian study and that a combination of 7 vitamins and minerals stabilized visual acuity loss in a small trial. Combined zinc and antioxidants slowed the progression of advanced age-related macular degeneration in high-risk persons. No consistent adverse effects of multivitamin and mineral supplements were evident. Limitations: Only randomized, controlled trials were considered for efficacy assessment. Special nutritional needs, such as use of folic acid by pregnant women to prevent birth defects, were not addressed. Findings may not apply to use of commercial multivitamin supplements by the general U.S. population. Conclusions: Evidence is insufficient to prove the presence or absence of benefits from use of multivitamin and mineral supplements to prevent cancer and chronic disease.
P131Mechanisms involved in early phase of cardiovascular response after mediastinal region irradiation
Authors: J Slezak, M Barancik, T Ravingerova, B Kura, A Lazou, R Kukreja, M Fulop, C Vinczencyova, L Okruhlicova
Journal: Cardiovascular Research (2014)

Despite modern radiotherapy techniques, treatment of oncological patients in some cases inevitably involves irradiation of normal tissues causing undesired side effects. Exposure of oncological patients to therapeutic doses of chest irradiation has been significant source of cardiovascular morbidity and mortality. The cellular response to radiation injury initiates an active process that ultimately leads to progressive damage. This process can be modulated by therapies directed at mitigation of undesirable events resulting from injury of normal tissue.
Analysis of Surgical Margins With the Molecular Marker eIF4E: A Prognostic Factor in Patients With Head and Neck Cancer
Authors: Cherie-Ann O. Nathan, Scott Franklin, Fleurette W. Abreo, Raja Nassar, Arrigo De Benedetti, Jonathan Glass
Journal: Journal of Clinical Oncology (1999)

Complete excision of cancer is guided by histologic assessment of surgical margins. Molecular markers may be more sensitive in identifying malignant cells. eIF4E, a eukaryotic protein synthesis initiation factor, is found elevated in all head and neck squamous cell cancers (HNSCC). In a preliminary study using Western blots and a retrospective study using immunohistochemistry, eIF4E elevation in histologically tumor-free surgical margins correlated with a higher local-regional recurrence. We wanted to confirm this hypothesis in a prospective study.Immunohistochemical analysis of surgical margins and tumors with an antibody to eIF4E was performed on all newly diagnosed HNSCC patients who underwent surgical resection for their disease between January 1996 and December 1997.All 65 patients had elevated levels of eIF4E in the tumors. Thirty-six patients (55%) had elevated eIF4E in histologically tumor-free margins, and 20 of these patients (56%) have had local-regional recu rrences. Twenty-nine patients (45%) had no elevation of eIF4E in the margins, and only two of these patients (6.9%) have had recurrences. Cox regression analysis showed that elevated eIF4E in the margins was an independent prognostic factor (P =.009) for recurrence. The Kaplan-Meier curves for the probability of nonrecurrence were significantly different for positive and negative eIF4E margins (P =. 0001, log-rank test).In histologically tumor-free surgical margins, elevated levels of eIF4E predict a significantly increased risk of recurrence. Elevated levels of eIF4E in tumor margins may identify patients who could benefit from additional therapy.
OC-056 Straight To Test Colonoscopy – A Viable Means Of Shortening Time To A Definitive Diagnosis
Authors: P Andrews, H Watson, M Mistry, M Machesney, E Seward
Journal: Gut (2014)

<h3>Introduction</h3> Endoscopy units face an increasing demand on their ability to meet timeliness targets. One way of managing demand is to work differently – and straight to test (STT) offers this. Patients with lower gastrointestinal (LGI) symptoms are telephone triaged by a trained specialist nurse direct to the appropriate endoscopic investigation, rather than attending clinic first. Clear benefits to the patient are a reduction in time to wait until definitive (endoscopic) diagnosis, to the Trust in freeing up out-patient staff to work elsewhere, and finally to the local health economy in terms of reduction in clinic costs <h3>Methods</h3> We followed a protocol outlined previously by the Dorset group<sup>.1</sup> Briefly, a specialist nurse assessed patients by phone and completed a symptom questionnaire. Patients were triaged according to symptoms and age; flexible sigmoidoscopy (&lt;40 yrs, anorectal symptoms only) or clinic (&gt;80 yrs and comorbidity, or major co-morbidity) or colonoscopy (everyone else). Appointments occured within 2 weeks for 2WW patients, or within 6 weeks for 18WW patients. The endoscopist was allowed to arrange further clinic review as was seen fit. A prospective database allowed capture of patient outcomes and demographic details, an estimate of financial benefit was made on the basis of standard charges for surgical (£172) or medical (£220) out-patient clinics. <h3>Results</h3> 89 patients passed through the pathway in the first three months, 64% female. Mean age 61 (range 32–88) yrs, 76% were on the 2WW pathway. Only 2% of the patients were triaged to flexible sigmoidoscopy, no patients required clinic assessment first. Mean wait on pathway for 2WW 12.4 days (range 4–20), and for 18WW 28.8 days (range 15–42), all breaches by patient choice. This represented a reduction from the normal pathway of 48% (2WW) and 67% (18WW). DNA rate was low at 1% (unit average 7%). Most common diagnoses were polyps (20%), diverticular disease (20%), IBD (9%). 1 patient had colorectal cancer – a further patient was diagnosed with pancreatic cancer on CT pneumocolon following a failed colonoscopy. 13% patients required clinic follow up. An estimated saving of £14156 was made from out-patient clinic slots that were no longer necessary, with cancellation of over seven new out-patient lists. <h3>Conclusion</h3> These data suggest that the introduction of a novel pathway for patients with LGI symptoms can produce significant benefits to the patient in terms of time to definitive endoscopic diagnosis. A financial benefit is also clear, as is the opportunity to redeploy clinic doctors elsewhere. <h3>Reference</h3> Wright HL. <i>Colorectal Dis</i> 2012;14:10 <h3>Disclosure of Interest</h3> None Declared.
Determinants of action potential duration in neonatal rat ventricle cells
Authors: B. Fermini, O. F Schanne
Journal: Cardiovascular Research (1991)

Study objective – The aim was to study the currents that determine the action potential duration in ventricular cells from neonatal rats. Design – Microelectrode measurements of action potentials from ventricle strips were compared with action potentials obtained from isolated myocytes with the whole cell patch clamp method in current clamp mode. Ionic currents were studied in myocytes in voltage clamp mode using recognised modulators of channel activity. Experimental material – Neonatal rats (2 d old) were decapitated and myocytes were prepared from the apical third of collagenase treated hearts. Measurements and main results – Modification of the action potential by 1.8-5.0 mM Ca, 2.0 mM Co, 8 mM 4-aminopyridine, 1.8 mM Sr, and 20 mM tetraethylammonium suggested the presence of the slowly inactivating Ca current ICa,L; an early outward current Ieo, and at least one other K current. Action potentials from myocytes and ventricular strips were comparable. Voltage clamp experiments were confirmatory and revealed currents with the following properties: (1) Ica,L: a Ca current with a current density of 21.7 μA-cm−2, activated between -30 and -20 mV, saturated at 1.8 Cao, inactivated faster at 5 than at 1.8 mM Ca0, more permeable to Ba and Sr than to Ca, and with Sr as charge carrier blocked by Ca; (2) Ieo: the peak current had a linear I/V relation between 0 and 70 mV and was abolished by 4 mM 4-aminopyridine; (3) IK1: the current was an inward rectifier that showed a relaxation at potentials negative to -90 mV. Conclusions – Action potentials obtained from neonatal rat ventricle with microelectrodes are comparable with those measured in myocytes in current clamp mode. The action potential duration is mainly determined by ICa,L, Ieo, and IK1, and there is no evidence for the presence of a delayed rectifier.
Polymorphisms of endotoxin pathway and endotoxin exposure:<i>in vitro</i>IgE synthesis and replication in a birth cohort
Authors: U. M. Sahiner, A. Semic-Jusufagic, J. A. Curtin, E. Birben, D. Belgrave, C. Sackesen, A. Simpson, T. S. Yavuz, C. A. Akdis, A. Custovic, O. Kalayci
Journal: Allergy (2014)

Background Genetic variants in endotoxin signaling pathway are important in modulating the effect of environmental endotoxin on asthma and atopic phenotypes. Our objective was to determine the single nucleotide polymorphisms (SNPs) in the endotoxin signaling pathway that may influence in vitro IgE synthesis and to investigate the relationship between these variants and endotoxin exposure in relation to the development of asthma and atopy in a birth cohort. Methods Peripheral blood mononuclear cells from 45 children with asthma were stimulated with 2 and 200 ng/ml lipopolysaccharide in vitro and IgE was measured in the culture supernatants. Children were genotyped for 121 SNPs from 30 genes in the endotoxin signaling pathway. Variants with a dose–response IgE production in relation to lipopolysaccharide (LPS) were selected for replication in a population-based birth cohort, in which we investigated the interaction between these SNPs and endotoxin exposure in relation to airway hyper-responsiveness, wheeze, and atopic sensitization. Results Twenty-one SNPs in nine genes (CD14, TLR4, IRF3, TRAF-6, TIRAP, TRIF, IKK-1, ST-2, SOCS1) were found to modulate the effect of endotoxin on in vitro IgE synthesis, with six displaying high linkage disequilibrium. Of the remaining 15 SNPs, for seven we found significant relationships between genotype and endotoxin exposure in the genetic association study in relation to symptomatic airway hyper-responsiveness (CD14-rs2915863 and rs2569191, TRIF-rs4807000), current wheeze (ST-2-rs17639215, IKK-1-rs2230804, and TRIF-rs4807000), and atopy (CD14-rs2915863 and rs2569192, TRAF-6-rs5030411, and IKK-1-rs2230804). Conclusions Variants in the endotoxin signaling pathway are important determinants of asthma and atopy. The genotype effect is a function of the environmental endotoxin exposure.