tbuckley/cabot-search huggingface dataset:
Clinical correlates of ‘BRCAness’ in triple-negative breast cancer of patients receiving adjuvant chemotherapy
Authors: A.M.M. Oonk, C. van Rijn, M.M. Smits, L. Mulder, N. Laddach, S.P. Savola, J. Wesseling, S. Rodenhuis, A.L.T. Imholz, E.H. Lips
Journal: Annals of Oncology (2012)
Tuberculosis and HIV co-infection in European Union and European Economic Area countries
Authors: L. Pimpin, L.N. Drumright, M.E. Kruijshaar, I. Abubakar, B. Rice, V. Delpech, V. Hollo, A. Amato-Gauci, D. Manissero, C. Ködmön
Journal: European Respiratory Journal (2011)

In order to ensure the availability of resources for tuberculosis (TB) and HIV management and control, it is imperative that countries monitor and plan for co-infection in order to identify, treat and prevent TB–HIV co-infection, thereby reducing TB burden and increasing the years of healthy life of people living with HIV. A systematic review was undertaken to determine the burden of TB–HIV infection in the European Union (EU) and European Economic Area (EEA). Data on the burden of HIV infection in TB patients and risk factors for TB–HIV co-infection in the EU/EEA were extracted from studies that collected information in 1996 and later, regardless of the year of initiation of data collection, and a narrative synthesis presented. The proportion of HIV-co-infected TB patients varied from 0 to 15%. Western and eastern countries had higher levels and increasing trends of infection over time compared with central EU/EEA countries. Groups at higher risk of TB–HIV co-infection were males, young adults, foreign-born persons, the homeless, injecting drug users and prisoners. Further research is needed into the burden and associated risk factors of co-infection in Europe, to help plan effective control measures. Increased HIV testing of TB patients and targeted and informed strategies for control and prevention could help curb the co-infection epidemic.
Sibutramine on Cardiovascular Outcome
Authors: André J. Scheen
Journal: Diabetes Care (2011)

Sibutramine, a combined norepinephrine and serotonin reuptake inhibitor, is effective in the management of obese patients requiring pharmacotherapy as part of a multimodal approach to weight loss. It improves insulin resistance markers, glucose metabolism, and atherogenic dyslipidemia in both diabetic and nondiabetic patients, most of these effects resulting from weight loss. However, sibutramine exerts a peripheral sympathomimetic effect that induces a moderate increase in heart rate and attenuates the reduction in blood pressure attributable to weight loss or even slightly increases blood pressure. Since 2002, several cardiovascular adverse events (hypertension, tachycardia, arrhythmias, myocardial infarction) were reported in sibutramine-treated patients. This led to a contraindication of the use of this antiobesity agent in patients with established coronary heart disease, previous stroke, heart failure, or cardiac arrhythmias. The recent Sibutramine Cardiovascular Outcomes Trial (SCOUT) confirmed that subjects with preexisting cardiovascular disease (CVD) on long-term (5 years) treatment with sibutramine (10–15 mg/day) had a significantly increased risk for nonfatal myocardial infarction and nonfatal stroke, but not cardiovascular death or all-cause mortality. Because the benefit of sibutramine as a weight loss aid seems not to outweigh the cardiovascular risks, the European Medicines Agency (EMEA) recommended the suspension of marketing authorizations for sibutramine across the European Union (EU). The U.S. Food and Drug Administration (FDA) first stated that the drug should carry a “black box” warning because of an increased risk of stroke and heart attack in patients with a history of CVD. In October 2010, however, sibutramine was withdrawn from the U.S. market. After SCOUT, concern still persists about the effect of sibutramine on cardiovascular outcome.

Obesity is a major cause of morbidity and mortality, predominantly through CVDs (1,2). The metabolic consequences of obesity, more particularly abdominal obesity associated with increased visceral adipose tissue, include atherogenic dyslipidemia, impaired glucose metabolism, hypertension, and …
Bronchodilator responsiveness and atopy in 5-10-yr-old coughers
Authors: S.A. McKenzie, M. Mylonopoulou, P.D. Bridge
Journal: European Respiratory Journal (2001)

Cough-variant asthma is considered by some to be an asthma phenotype. Bronchodilator responsiveness (BDR) is an undisputed feature of asthma. Of school-aged wheezers, 90% are atopic. Are school-aged coughers who demonstrate BDR also atopic? If so, then it would be reasonable to reserve the diagnosis cough-variant asthma for this particular group. Airway resistance was measured by the interrupter technique (<i>R</i><sub>int</sub>) before and after salbutamol in controls (n=73), coughers (n=63) and previous wheezers (n=63) aged 5–10 yrs. Immunoglobulin (Ig)-E was measured in coughers and wheezers. BDR was expressed as the ratio baseline:post-salbutamol <i>R</i><sub>int</sub>. Groups were of similar age (mean 6.7, range 5–9.9 yrs). Geometric mean baseline <i>R</i><sub>int</sub> was similar in controls and coughers (0.66 and 0.68 kPa·L<sup>−1</sup>·s), but the baseline <i>R</i><sub>int</sub> for wheezers (0.73 kPa·L<sup>−1</sup>·s) was greater than that for controls (p=0.05) but not significantly different from coughers (p=0.17). Geometric mean BDR in coughers was 1.22, controls 1.13 and wheezers 1.30 (p=0.01 for coughers and controls; p=0.08 for coughers and wheezers; p&lt;0.001 for controls and wheezers). IgE was lower in coughers than wheezers (geometric means 36 and 364 International Units (IU)·L<sup>−1</sup>, p&lt;0.001) and was unrelated to BDR in both groups. In summary, atopy, and not bronchodilator responsiveness, distinguishes groups of coughers from groups of wheezers. A diagnosis of cough-variant asthma cannot be reserved for even those school-aged coughers, who demonstrate bronchodilator responsiveness.
Effect of excess alpha-hemoglobin chains on cellular and membrane oxidation in model beta-thalassemic erythrocytes.
Authors: M D Scott, J J van den Berg, T Repka, P Rouyer-Fessard, R P Hebbel, Y Beuzard, B H Lubin
Journal: Journal of Clinical Investigation (1993)

While red cells from individuals with beta thalassemias are characterized by evidence of elevated in vivo oxidation, it has not been possible to directly examine the relationship between excess alpha-hemoglobin chains and the observed oxidant damage. To investigate the oxidative effects of unpaired alpha-hemoglobin chains, purified alpha-hemoglobin chains were entrapped within normal erythrocytes. These "model" beta-thalassemic cells generated significantly (P < 0.001) greater amounts of methemoglobin and intracellular hydrogen peroxide than did control cells. This resulted in significant time-dependent decreases in the protein concentrations and reduced thiol content of spectrin and ankyrin. These abnormalities correlated with the rate of alpha-hemoglobin chain autoxidation and appearance of membrane-bound globin. In addition, alpha-hemoglobin chain loading resulted in a direct decrease (38.5%) in catalase activity. In the absence of exogenous oxidants, membrane peroxidation and vitamin E levels were unaltered. However, when challenged with an external oxidant, lipid peroxidation and vitamin E oxidation were significantly (P < 0.001) enhanced in the alpha-hemoglobin chain-loaded cells. Membrane bound heme and iron were also significantly elevated (P < 0.001) in the alpha-hemoglobin chain-loaded cells and lipid peroxidation could be partially inhibited by entrapment of an iron chelator. In contrast, chemical inhibition of cellular catalase activity enhanced the detrimental effects of entrapped alpha-hemoglobin chains. In summary, entrapment of purified alpha-hemoglobin chains within normal erythrocytes significantly enhanced cellular oxidant stress and resulted in pathological changes characteristic of thalassemic cells in vivo. This model provides a means by which the pathophysiological effects of excess alpha-hemoglobin chains can be examined.
P212 Should intercostal tube drainage be the first intervention in the management of primary spontaneous pneumothorax with complete lung collapse?: Abstract P212 Table 1 -
Authors: MB Ganaie, S Bikmalla, MA Khalil, MA Afridi, M Haris, IR Hussain
Journal: Thorax (2013)

<h3>Introduction and Objectives</h3> Primary Spontaneous Pneumothorax (PSP) is a common presentation with significant variation in severity and treatment strategies globally. There is no differentiation between ‘large’ PSP with complete lung collapse and ‘large pneumothorax’ in the current treatment algorithms. Previous studies comparing needle aspiration (NA) and intercostal tube (ICT) drainage for all PSP requiring intervention have shown no significant difference in immediate success rate, early failure rate and length of stay. We aimed to compare NA with ICT as the first intervention in those with complete lung collapse. <h3>Methods</h3> Retrospective, observational study of 212 consecutive pneumothorax episodes between January 2012 and December 2012. Those with secondary spontaneous pneumothorax (SSP), history of trauma and iatrogenic pneumothorax were excluded. Pneumothorax with no visible aerated ipsilateral lung on plain chest radiograph was defined as ‘complete lung collapse’. Patient records and plain chest radiographs on PACS were reviewed and data was analysed. Values of p &lt; 0.05 were considered statistically significant. <h3>Results</h3> Of the 212 episodes, 51 (33%) were PSP. Median age was 29 years (IQR 22–38); male 33(75%), female 18(25%). 5(1%) were observed; 28(55%) had NA and 18(36%) had ICT as 1<sup>st</sup> intervention. NA was successful in 13(46%) which is comparable to previous studies. 33(65%) required hospitalisation and median length of stay (LOS) for all PSP was 4 days. 18(35%) required definitive surgical intervention. <h3>Conclusion</h3> Our results show significantly better lung re-inflation rates with ICT as the first intervention in the management of PSP with complete lung collapse and there was no added benefit in performing NA. We propose a further sub-group of PSP with complete lung collapse in which NA should not be attempted, however well-designed prospective studies are required to validate this.
Efficacy of Oral Adjuvant Therapy After Resection of Colorectal Cancer: 5-Year Results From Three Randomized Trials
Authors: Junichi Sakamoto, Yasuo Ohashi, Chikuma Hamada, Marc Buyse, Tomasz Burzykowski, Pascal Piedbois, Rectum
Journal: Journal of Clinical Oncology (2004)

Adjuvant therapy of colorectal cancer with oral fluorinated pyrimidines is attractive because of its ease of administration and good tolerability. The purpose of this meta-analysis is to assess the survival and disease-free survival benefits of treating patients after surgical resection of a primary colorectal tumor with oral fluoropyrimidines for 1 year.This meta-analysis was performed on individual data from three randomized trials conducted by the Japanese Foundation for Multidisciplinary Treatment for Cancer involving a total of 5,233 patients with stages I to III colorectal cancer.The overall hazard ratio in favor of oral therapy was 0.89 for survival (95% CI, 0.80 to 0.99; P =.04), and 0.85 for disease-free survival (95% CI, 0.77 to 0.93; P <.001). Thus oral therapy reduced the risk of death by 11% and the risk of recurrence or death by 15%. There was no significant heterogeneity between trials, nor did the benefit of oral therapy depend on tumor stage (I, II, or III), tumor site (rectum or colon), patient age, or patient sex.Oral fluoropyrimidines improve disease-free survival and survival of patients after resection of early-stage colorectal cancer. These observations support the use of these agents alone after resection of early-stage disease, as well as further testing of oral agents in combination with new drugs that have recently shown antitumor activity in advanced colorectal cancer.
Cytotoxic T cells specific for glutamic acid decarboxylase in autoimmune diabetes.
Authors: P Panina-Bordignon, R Lang, P M van Endert, E Benazzi, A M Felix, R M Pastore, G A Spinas, F Sinigaglia
Journal: The Journal of Experimental Medicine (1995)

Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease that results in the destruction of the pancreatic islet beta cells. Glutamic acid decarboxylase (GAD) has been recently indicated as a key autoantigen in the induction of IDDM in nonobese diabetic mice. In human diabetes, the mechanism by which the beta cells are destroyed is still unknown. Here we report the first evidence for the presence of GAD-specific cytotoxic T cells in asymptomatic and recent diabetic patients. GAD65 peptides displaying the human histocompatibility leukocyte antigen (HLA)-A*0201 binding motif have been synthesized. One of these peptides, GAD114-123, binds to HLA-A*0201 molecules in an HLA assembly assay. Peripheral blood mononuclear cells from individuals with preclinical IDDM, recent-onset IDDM, and from healthy controls were stimulated in vitro with the selected peptide in the presence of autologous antigen-presenting cells. In three cases (one preclinical IDDM and two recent-onset IDDM), we detected specific killing of autologous antigen-presenting cells when incubated with GAD114-123 peptide or when infected with a recombinant vaccinia virus expressing GAD65. These patients were the only three carrying the HLA-A*0201 allele among the subjects studied. Our finding suggests that GAD-specific cytotoxic T lymphocytes may play a critical role in the initial events of IDDM.
Reboxetine for acute treatment of major depression: systematic review and meta-analysis of published and unpublished placebo and selective serotonin reuptake inhibitor controlled trials
Authors: D. Eyding, M. Lelgemann, U. Grouven, M. Harter, M. Kromp, T. Kaiser, M. F. Kerekes, M. Gerken, B. Wieseler
Journal: BMJ (2010)

<b>Objectives</b> To assess the benefits and harms of reboxetine versus placebo or selective serotonin reuptake inhibitors (SSRIs) in the acute treatment of depression, and to measure the impact of potential publication bias in trials of reboxetine. <b>Design</b> Systematic review and meta-analysis including unpublished data. <b>Data sources</b> Bibliographic databases (Medline, Embase, PsycINFO, BIOSIS, and Cochrane Library), clinical trial registries, trial results databases, and regulatory authority websites up until February 2009, as well as unpublished data from the manufacturer of reboxetine (Pfizer, Berlin). <b>Eligibility criteria</b> Double blind, randomised, controlled trials of acute treatment (six weeks or more) with reboxetine versus placebo or SSRIs in adults with major depression. <b>Outcome measures</b> Remission and response rates (benefit outcomes), as well as rates of patients with at least one adverse event and withdrawals owing to adverse events (harm outcomes). <b>Data extraction and data synthesis</b> The procedures for data extraction and assessment of risk of bias were always conducted by one person and checked by another. If feasible, data were pooled by meta-analyses (random effects model). Publication bias was measured by comparing results of published and unpublished trials. <b>Results</b> We analysed 13 acute treatment trials that were placebo controlled, SSRI controlled, or both, which included 4098 patients. Data on 74% (3033/4098) of these patients were unpublished. In the reboxetine versus placebo comparison, no significant differences in remission rates were shown (odds ratio 1.17, 95% confidence interval 0.91 to 1.51; P=0.216). Substantial heterogeneity (I<sup>2</sup>=67.3%) was shown in the meta-analysis of the eight trials that investigated response rates for reboxetine versus placebo. A sensitivity analysis that excluded a small inpatient trial showed no significant difference in response rates between patients receiving reboxetine and those receiving placebo (OR 1.24, 95% CI 0.98 to 1.56; P=0.071; I<sup>2</sup>=42.1%). Reboxetine was inferior to SSRIs (fluoxetine, paroxetine, and citalopram) for remission rates (OR 0.80, 95% CI 0.67 to 0.96; P=0.015) and response rates (OR 0.80, 95% CI 0.67 to 0.95; P=0.01). Reboxetine was inferior to placebo for both harm outcomes (P&lt;0.001 for both), and to fluoxetine for withdrawals owing to adverse events (OR 1.79, 95% CI 1.06 to 3.05; P=0.031). Published data overestimated the benefit of reboxetine versus placebo by up to 115% and reboxetine versus SSRIs by up to 23%, and also underestimated harm. <b>Conclusions</b> Reboxetine is, overall, an ineffective and potentially harmful antidepressant. Published evidence is affected by publication bias, underlining the urgent need for mandatory publication of trial data.
Adjuvant radiotherapy versus observation alone for patients at risk of lymph-node field relapse after therapeutic lymphadenectomy for melanoma: a randomised trial
Authors: Bryan H Burmeister, Michael A Henderson, Jill Ainslie, Richard Fisher, Juliana Di Iulio, B Mark Smithers, Angela Hong, Kerwin Shannon, Richard A Scolyer, Scott Carruthers, Brendon J Coventry, Scott Babington, Joao Duprat, Harald J Hoekstra, John F Thompson
Journal: The Lancet Oncology (2012)
Association of Physical Activity and Serum Insulin Concentrations in Two Populations at High Risk for Type 2 Diabetes but Differing by BMI
Authors: Andrea M. Kriska, Mark A. Pereira, Robert L. Hanson, Maximilian P. de Courten, Paul Z. Zimmet, K. George M.M. Alberti, Pierrot Chitson, Peter H. Bennett, K.M. Venkat Narayan, William C. Knowler
Journal: Diabetes Care (2001)

OBJECTIVE—Physical activity and insulin sensitivity are related in epidemiological studies, but the consistency of this finding among populations that greatly differ in body size is uncertain. The present multiethnic epidemiological study examined whether physical activity was related to insulin concentrations in two populations at high risk for diabetes that greatly differ by location, ethnic group, and BMI. RESEARCH DESIGN AND METHODS—The study populations consisted of 2,321 nondiabetic Pima Indian men and women aged 15–59 years from Arizona and 2,716 nondiabetic men and women aged 35–54 years from Mauritius. Insulin sensitivity was estimated by mean insulin concentration (average of the fasting and postload insulin), and total (i.e., leisure and occupational) physical activity was assessed by questionnaire. RESULTS—Pima men and women who were more active had significantly (P &amp;lt; 0.05) lower mean insulin concentrations than those less active (BMI and age-adjusted means were 179 vs. 200 and 237 vs. 268 pmol/l). Similar findings were noted in Mauritian men and women (94 vs. 122 and 127 vs. 148 pmol/l). In both populations, activity remained significantly associated with mean insulin concentration controlled for age, BMI, waist-to-thigh or waist-to-hip ratio, and mean glucose concentrations. CONCLUSIONS—Physical activity was negatively associated with insulin concentrations both in the Pima Indians, who tend to be overweight, and in Mauritians, who are leaner. These findings suggest a beneficial role of activity on insulin sensitivity that is separate from any influence of activity on body composition.
Frailty Is Independently Associated With Short-Term Outcomes for Elderly Patients With Non–ST-Segment Elevation Myocardial Infarction
Authors: Niklas Ekerstad, Eva Swahn, Magnus Janzon, Joakim Alfredsson, Rurik Löfmark, Marcus Lindenberger, Per Carlsson
Journal: Circulation (2011)

Background— For the large and growing population of elderly patients with cardiovascular disease, it is important to identify clinically relevant measures of biological age and their contribution to risk. Frailty is an emerging concept in medicine denoting increased vulnerability and decreased physiological reserves. We analyzed the manner in which the variable frailty predicts short-term outcomes for elderly non–ST-segment elevation myocardial infarction patients. Methods and Results— Patients aged ≥75 years, with diagnosed non–ST-segment elevation myocardial infarction were included at 3 centers, and clinical data including judgment of frailty were collected prospectively. Frailty was defined according to the Canadian Study of Health and Aging Clinical Frailty Scale. The impact of the comorbid conditions on risk was quantified by the coronary artery disease–specific index. Of 307 patients, 149 (48.5%) were considered frail. By multiple logistic regression, frailty was found to be strongly and independently associated with risk for the primary composite outcome (death from any cause, myocardial reinfarction, revascularization due to ischemia, hospitalization for any cause, major bleeding, stroke/transient ischemic attack, and need for dialysis up to 1 month after inclusion) (odds ratio, 2.2; 95% confidence interval, 1.3–3.7), in-hospital mortality (odds ratio, 4.6; 95% confidence interval, 1.3–16.8), and 1-month mortality (odds ratio, 4.7; 95% confidence interval, 1.7–13.0). Conclusions— Frailty is strongly and independently associated with in-hospital mortality, 1-month mortality, prolonged hospital care, and the primary composite outcome. The combined use of frailty and comorbidity may constitute an ultimate risk prediction concept in regard to cardiovascular patients with complex needs. Clinical Trial Registration— http://www.clinicaltrials.gov . Unique identifier: NCT01049997.
Plasma Folate, Vitamin B6, Vitamin B12, and Homocysteine and Pancreatic Cancer Risk in Four Large Cohorts
Authors: Eva Schernhammer, Brian Wolpin, Nader Rifai, Barbara Cochrane, Jo Ann Manson, Jing Ma, Ed Giovannucci, Cynthia Thomson, Meir J. Stampfer, Charles Fuchs
Journal: Cancer Research (2007)

Abstract Folate deficiency induces DNA breaks and may alter cellular capacity for mutation and epigenetic methylation. Few studies have examined the influence of one-carbon nutrients on pancreatic cancer risk, although recent studies suggest a potential protective effect for one-carbon nutrients from food sources, but not from supplements. We conducted a prospective nested case-control study to examine plasma concentrations of folate, vitamin B6 [whose main circulating form is pyridoxal-5′-phosphate (PLP)], vitamin B12, and homocysteine in relationship to pancreatic cancer, using four large prospective cohorts. Multivariable adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using conditional logistic regression. All statistical tests were two sided. Among 208 cases and 623 controls, we observed no association between folate, PLP, vitamin B12, or homocysteine and pancreatic cancer risk. Comparing the highest to lowest quartiles of plasma concentration, the ORs were 1.20 (95% CI, 0.76–1.91) for folate, 0.80 (95% CI, 0.51–1.25) for B6, 0.91 (95% CI, 0.57–1.46) for B12, and 1.43 (95% CI, 0.90–2.28) for homocysteine. In analyses restricted to nonusers of multivitamins, we observe a modest inverse trend between folate, PLP, and B12 and pancreatic cancer risk. In contrast, no such inverse associations were observed among study subjects who reported multivitamin supplement use. Among all participants, plasma levels of folate, B6, B12, and homocysteine were not associated with a significant reduction in the risk of pancreatic cancer. Among participants who obtain these factors exclusively through dietary sources, there may be an inverse relation between circulating folate, B6, and B12 and risk. [Cancer Res 2007;67(11):5553–60]
The motile and invasive capacity of human endometrial stromal cells: implications for normal and impaired reproductive function
Authors: Charlotte H.E. Weimar, Nick S. Macklon, Emiel D. Post Uiterweer, Jan J. Brosens, Birgit Gellersen
Journal: Human Reproduction Update (2013)

BACKGROUNDMechanisms underlying early reproductive loss in the human are beginning to be elucidated. The migratory and invasive capacity of human endometrial stromal cells (ESCs) is increasingly recognized to contribute to the intense tissue remodelling associated with embryo implantation, trophoblast invasion and endometrial regeneration. In this review, we examine the signals and mechanisms that control ESC migration and invasion and assess how deregulation of these cell functions contributes to common reproductive disorders.