tbuckley/cabot-search huggingface dataset:
Early Changes in Functional Dynamic Magnetic Resonance Imaging Predict for Pathologic Response to Neoadjuvant Chemotherapy in Primary Breast Cancer
Authors: Mei-Lin W. Ah-See, Andreas Makris, N. Jane Taylor, Mark Harrison, Paul I. Richman, Russell J. Burcombe, J. James Stirling, James A. d'Arcy, David J. Collins, Michael R. Pittam, Duraisamy Ravichandran, Anwar R. Padhani
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) allows noninvasive, in vivo measurements of tissue microvessel perfusion and permeability. We examined whether DCE-MRI done after two cycles of neoadjuvant chemotherapy could predict final clinical and pathologic response in primary breast cancers. Experimental Design: Thirty-seven patients with primary breast cancer, due to receive six cycles of neoadjuvant 5-fluorouracil, epirubicin and cyclophosphamide chemotherapy, were examined using DCE-MRI before neoadjuvant chemotherapy and after two cycles of treatment. Changes in DCE-MRI kinetic parameters (Ktrans, kep, ve, MaxGd, rBV, rBF, MTT) were correlated with the final clinical and pathologic response to neoadjuvant chemotherapy. Test-retest variability was used to determine individual patient response. Results: Twenty-eight patients were evaluable for response (19 clinical responders and 9 nonresponders; 11 pathologic responders and 17 nonresponders). Changes in the DCE-MRI kinetic parameters Ktrans, kep, MaxGd, rBV, and rBF were significantly correlated with both final clinical and pathologic response (P &amp;lt; 0.01). Change in Ktrans was the best predictor of pathologic nonresponse (area under the receiver operating characteristic curve, 0.93; sensitivity, 94%; specificity, 82%), correctly identifying 94% of nonresponders and 73% of responders. Change in MRI-derived tumor size did not predict for pathologic response. Conclusion: Changes in breast tumor microvessel functionality as depicted by DCE-MRI early on after starting anthracycline-based neoadjuvant chemotherapy can predict final clinical and pathologic response. The ability to identify nonresponders early may allow the selection of patients who may benefit from a therapy change.
Association of deprivation, ethnicity, and sex with quality indicators for diabetes: population based survey of 53 000 patients in primary care
Authors: J. Hippisley-Cox
Journal: BMJ (2004)

Objectives To determine the effect of deprivation and ethnicity on the achievement of quality indicators for patients with diabetes and the extent of any inequalities between the sexes. Design Population based cross sectional survey using electronic general practice records. Setting 237 UK practices contributing to the QRESEARCH database. Participants 54 180 patients with diabetes, derived from a population of 1.8 million patients. Main outcome measures Adjusted odds ratios for 18 indicators for diabetes from the new general medical services contract for UK general practitioners and comparisons between patients from the most deprived and most affluent fifths (areas of high and low ethnicity) and between men and women. Results The prevalence of diabetes was 3.0%, and there was a large variation between practices in achievement of indicators. Compared with patients from affluent areas, those from deprived areas were less likely to have body mass index and smoking status recorded. They were also less likely to have records for HbA1c concentration; an HbA1c value < 7.5% or < 10%; retinal screening; blood pressure; testing for neuropathy or microalbuminuria, or flu vaccination. Compared with patients from areas of low ethnicity those from areas of high ethnicity were less likely to have many measures recorded. Women were significantly less likely to have records for body mass index; pulses; blood pressure values below 145/85 mm Hg; testing for microalbuminuria; serum cholesterol concentration; serum cholesterol values < 5 mmol/l; and angiotensin converting enzyme inhibitors given in the presence of proteinuria or microalbuminuria. Conclusions Practices in areas of high deprivation and high ethnicity will have to work harder to achieve the quality indicators for diabetes, and it is possible that those practices that most need the resources are the ones least likely to get them.
Filaggrin loss-of-function mutations and incident cancer: a population-based study
Authors: T. Skaaby, L.L.N. Husemoen, J.P. Thyssen, M. Meldgaard, B.H. Thuesen, C. Pisinger, T. Jørgensen, K. Carlsen, J.D. Johansen, T. Menné, P.B. Szecsi, S. Stender, A. Linneberg
Journal: British Journal of Dermatology (2014)

Loss-of-function mutations in the filaggrin gene (FLG) could have opposing effects on cancer risk, as mutations are associated with both 10% higher serum vitamin D levels, which may protect against cancer, and with impaired skin barrier function, which may lead to higher cancer susceptibility.To investigate the association of the FLG genotype and cancer types in four population-based cohorts.A total of 13,376 individuals were genotyped for FLG mutations. Information on cancer was obtained from the Danish Cancer Registry. Persons with a history of cancer at baseline were excluded from prospective analyses.There were 1339 incident cancers (median follow-up 11·4 years). The hazard ratios (HRs) and 95% confidence intervals (CIs) for FLG mutation carriers vs. wild types were: for any cancer (HR 0·95, 95% CI 0·78-1·16), any cancer excluding nonmelanoma skin cancer (NMSC) (HR 1·05, 95% CI 0·84-1·31), head and neck cancer (HR 1·72, 95% CI 0·71-4·15), colorectal cancer (HR 0·82, 95% CI 0·44-1·52), bronchus and lung cancer (HR 1·34, 95% CI 0·77-2·33), breast cancer (HR 0·58, 95% CI 0·30-1·14), uterine cancer (HR 0·42, 95% CI 0·06-3·10), prostate cancer (HR 1·09, 95% CI 0·61-1·94), urinary cancer (HR 1·30, 95% CI 0·51-3·29), malignant melanoma (HR 1·03, 95% CI 0·41-2·58) and NMSC (HR 0·70, 95% CI 0·47-1·05). Among participants aged over 60 years at baseline, we found statistically significant lower risks of all cancers and NMSC among FLG mutation carriers.The only significant associations between FLG loss-of-function mutations and cancer were in subgroup analyses.
TCT-739 Effect of Ticagrelor on the Outcomes of Patients With Prior Coronary Artery Bypass Graft Surgery: Insights From The PLATelet inhibition and patient Outcomes (PLATO) trial
Authors: Emmanouil Brilakis, Claes Held, Bernhard Meier, Frank Cools, Marc Claeys, Jan Cornel, Philip Aylward, Basil Lewis, Douglas Weaver, Gunnar Brandrup- Wognsen, Susanna Stevens, Lars Wallentin, Stefan James
Journal: Journal of the American College of Cardiology (2012)
IL-1 Mediates Pulmonary and Systemic Inflammatory Responses to Chorioamnionitis Induced by Lipopolysaccharide
Authors: Suhas G. Kallapur, Ilias Nitsos, Timothy J. M. Moss, Graeme R. Polglase, J. Jane Pillow, Fook-Choe Cheah, Boris W. Kramer, John P. Newnham, Machiko Ikegami, Alan H. Jobe
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Chorioamnionitis frequently associates with preterm delivery and increased amniotic fluid IL-1, and causes fetal lung and systemic inflammation. However, chorioamnionitis is also associated with a paradoxical reduction in the incidence of surfactant deficiency-related respiratory distress syndrome in preterm infants.To identify the role of IL-1 signaling in the mediation of pulmonary and systemic inflammation and lung maturation in a fetal sheep model of lipopolysaccharide (LPS) induced chorioamnionitis.After confirming the efficacy of recombinant human IL-1 receptor antagonist (rhIL-1ra), fetal sheep were exposed to intraamniotic (IA) injections of Escherichia coli LPS with or without prior IA injections of rhIL-1ra. Preterm lambs were delivered at 82% of term gestation.rhIL-1ra decreased IA LPS-induced lung inflammation assessed by decreased lung neutrophil and monocyte influx, inducible nitric oxide synthase expression, lung IL-6 and IL-1beta mRNA expression, and airway myeloperoxidase concentrations. rhIL-1ra inhibited IA LPS-induced fetal systemic inflammation assessed by decreased plasma IL-8, protein carbonyls, blood neutrophilia, and the expression of serum amyloid A3 mRNA in the liver. rhIL-1ra also partially blocked the lung maturational effects of IA LPS. Therefore blockade of IL-1 signaling in the amniotic compartment inhibited fetal lung and systemic inflammation and lung maturation in response to LPS-induced chorioamnionitis.IL-1 plays a central role in the pathogenesis of chorioamnionitis-induced fetal inflammatory responses.
Echocardiographic Markers of Elevated Pulmonary Pressure and Left Ventricular Diastolic Dysfunction Are Associated With Exercise Intolerance in Adults and Adolescents With Homozygous Sickle Cell Anemia in the United States and United Kingdom
Authors: Vandana Sachdev, Gregory J. Kato, J. Simon R. Gibbs, Robyn J. Barst, Roberto F. Machado, Mehdi Nouraie, Kathryn L. Hassell, Jane A. Little, Dean E. Schraufnagel, Lakshmanan Krishnamurti, Enrico M. Novelli, Reda E. Girgis, Claudia R. Morris, Erika Berman Rosenzweig, David B. Badesch, Sophie Lanzkron, Oswaldo L. Castro, James G. Taylor, Hwaida Hannoush, Jonathan C. Goldsmith, Mark T. Gladwin, Victor R. Gordeuk
Journal: Circulation (2011)

Background— Noninvasively assessed pulmonary pressure elevations and left ventricular (LV) diastolic dysfunction are associated with increased mortality in adults with sickle cell disease, but their relationship to exercise intolerance has not been evaluated prospectively. Methods and Results— Echocardiography, 6-minute walk distance, hemolytic rate, and serum concentrations of ferritin and erythropoietin were evaluated in a cohort of 483 subjects with homozygous hemoglobin S in the US and UK Walk–Treatment of Pulmonary Hypertension and Sickle Cell Disease with Sildenafil Therapy (Walk-PHaSST) study. Tricuspid regurgitation velocity, which reflects systolic pulmonary artery pressure, was 2.7 to &lt;3.0 m/s (mean±SD, 2.8±0.1) in 26% of the subjects and ≥3.0 m/s (mean±SD, 3.4±0.4) in 11%. The LV lateral E/e′ ratio, which has been shown to reflect LV filling pressure in other conditions but has not been studied in sickle cell disease, was significantly higher in the groups with tricuspid regurgitation velocity ≥2.7 m/s. Increased hemolysis ( P &lt;0.0001), LV lateral E/e′ ratio ( P =0.0001), blood urea nitrogen ( P =0.0002), and erythropoietin ( P =0.002) were independently associated with an increased tricuspid regurgitation velocity. Furthermore, female sex ( P &lt;0.0001), older age ( P &lt;0.0001), LV lateral E/e′ ratio ( P =0.014), and tricuspid regurgitation velocity ( P =0.019) were independent predictors of a shorter 6-minute walk distance. Conclusions— Echocardiography-estimated elevated pulmonary artery systolic pressure and LV lateral E/e′ ratio were independently associated with poor exercise capacity in a large cohort of patients with sickle cell anemia. Controlled trials investigating whether strategies to prevent or delay pulmonary hypertension and/or LV diastolic dysfunction will improve exercise capacity and long-term outcomes in sickle cell anemia should be considered. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00492531.
A prognostic model in patients treated for metastatic gastric cancer with second-line chemotherapy
Authors: D. Kanagavel, I.A. Pokataev, M.Y. Fedyanin, A.A. Tryakin, I.S. Bazin, M.N. Narimanov, E.S. Yakovleva, A.M. Garin, S.A. Tjulandin
Journal: Annals of Oncology (2010)
Fibrinopeptide A is released into the coronary circulation after coronary spasm.
Authors: S Oshima, H Yasue, H Ogawa, K Okumura, K Matsuyama
Journal: Circulation (1990)

To examine whether acute myocardial ischemia activates the coagulation system and platelet activation in the coronary circulation, we measured plasma levels of fibrinopeptide A and beta-thromboglobulin in the coronary sinus and the aortic root simultaneously in 15 patients with coronary spastic angina before and after the left coronary spasm induced by intracoronary injection of acetylcholine and in 15 patients with stable exertional angina before and after acute myocardial ischemia induced by rapid atrial pacing. Fifteen patients with chest pain but normal coronary arteries and no coronary spasm served as controls. The coronary sinus-arterial difference of fibrinopeptide A increased markedly (p less than 0.001) from 0.1 +/- 0.2 to 4.3 +/- 0.7 ng/ml after the anginal attacks in the coronary spastic angina group. However, fibrinopeptide A levels remained unchanged after the attacks in the stable exertional angina group and after intracoronary injection of acetylcholine in the control group. Plasma beta-thromboglobulin levels remained unchanged after the attacks in both patient groups and after acetylcholine in the control group. Our data indicate that coronary spasm induces thrombin generation and may lead to thrombus formation in the coronary artery involved, but pacing-induced ischemia does not activate the coagulation system.
Contributions of Coronary Perfusion Pressure, Metabolic Acidosis and Adrenergic Factors to the Reduction of Myocardial Contractility during Hemorrhagic Shock in the Cat
Authors: HOWARD W. SIEGEL, S. EVANS DOWNING
Journal: Circulation Research (1970)

The contributions of metabolic acidosis, coronary perfusion pressure (CPP) and adrenergic support to left ventricular performance during hemorrhagic shock at aortic pressure (AP) of 30 ± 5 mm Hg were evaluated in cats in which AP, cardiac output (CO), and heart rate (HR) were controlled, and arterial pH, Po 2 and Pco 2 were continuously monitored. After 2 hours of shock, the stroke volume (SV), ejected at end-diastolic pressure of 10 cm H 2 O (SV 10 ), was irreversibly reduced to 46 ± 4% (P &lt; .001) of initial values (arterial pH 6.93 ± .05). In control animals SV 10 after 2 hours was 86 ± 6% (pH 7.32 ± .07). Eight animals were subject to shock, but their CPP was held at 100 mm Hg. These showed no difference in SV 10 from controls after 2 hours, although the pH had fallen to 6.90 ± .05. Reduction of CPP in these animals without correction of pH resulted in a rapid fall of SV 10 . In 10 animals subjected to shock for 2 hours, the arterial pH was maintained near 7.40 by infusion of Tris buffer. Five showed no greater reduction of SV 10 than the controls, and five became severely depressed. In five cats subjected to beta-receptor blockade, hemorrhagic shock (pH 7.40) produced a rapid fall of SV 10 which initially could be reversed by reelevation of AP. In less than 15 minutes, the SV 10 depression became irreversible. Thus, shock (2 hours) and associated metabolic acidosis is detrimental to ventricular contractility only if CPP is also reduced. The contribution of acidosis may be related to the amount of sympathetic support during shock. With beta-receptor blockade, shock results in a marked reduction in SV 10 , even in the absence of metabolic acidosis.
Congenital Spinal Palsy
Authors: D. F. E. Nash
Journal: BMJ (1956)

Premature InfantsThis group contains all infants under 52 lb.(2.5 kg.) birth weight, irrespective of the expected date of delivery.The systolic pressures that were recorded ranged from 35 to 70 mm.Hg, with a mean of 54.The lower end of the range was recorded in two infants who survived only three days, and it should also be noted that one infant with a pressure of 50 mm.Hg died on the first day.As shown in Figs. 2 and3 the systolic pressure at birth was related to birth weight but not to maturity.The premature infants attained values not significantly different from those of full-time infants by the third month, and the highest pressure recorded in any infant, 105 mm.Hg, at 6 months was in a prematurely born infant with a pressure of 50 mm.Hg at birth.
Spontaneous pneumothorax in a 24-year-old female
Authors: E. Battistini
Journal: European Respiratory Journal (2005)

A 24-yr-old Caucasian female was evaluated in May, 2003 at the San Martino hospital, Genoa, Italy, for the presence of ''sudden onset'' chest pain and nonproductive cough.Past medical history was only characterised by the presence of frequent headaches.The patient had been playing competitive tennis from the age of 6-20 yrs and, after retirement from competitions, had been smoking cigarettes (0.5 pack?day -1 ) for the last 4 yrs.The patient was nulliparous and reported the use of oral contraceptive in the last 3 yrs.Any suggestion of respiratory symptoms, including cough, shortness of breath or physical limitations during exercise were denied.
Inflammatory Markers at the Site of Ruptured Plaque in Acute Myocardial Infarction
Authors: Willibald Maier, Lukas A. Altwegg, Roberto Corti, Steffen Gay, Martin Hersberger, Friedrich E. Maly, Gabor Sütsch, Marco Roffi, Michel Neidhart, Franz R. Eberli, Felix C. Tanner, Sharon Gobbi, Arnold von Eckardstein, Thomas F. Lüscher
Journal: Circulation (2005)

Background— Acute myocardial infarction (AMI) is associated with inflammation. However, it remains unclear whether it originates from the ruptured plaque or represents a systemic process. Methods and Results— In 42 patients with AMI, a balloon-based embolization protection device and aspiration catheter (PercuSurge) were used during acute coronary interventions. Samples from the site of the ruptured plaque were taken under distal balloon occlusion. Systemic samples were taken from the aorta. Sera, plaques, and thrombi were analyzed for inflammatory markers and lipoproteins. Systemic levels of C-reactive protein (CRP), interleukin-6 (IL-6), and serum amyloid A (SAA) in the aorta amounted to 3.0 mg/L, 5.0 ng/L, and 22.1 mg/L, respectively (interquartile ranges [IQRs], 1.1 to 7.4 mg/L, 5.0 to 6.5 ng/L, and 13.9 to 27.0 mg/L, respectively). In blood surrounding ruptured plaques, local levels of IL-6 (8.9 ng/L; IQR, 5.0 to 16.9 ng/L) and SAA (24.3 mg/L; IQR, 16.3 to 44.0 mg/L) were significantly higher, whereas CRP levels (2.5 mg/L; IQR, 0.9 to 7.7 mg/L) were decreased compared with the aorta (all P &lt;0.0001). The coronary levels of IL-6 determined in vivo showed biological activity in vitro. Harvested thrombus contained CD68-positive monocytes expressing IL-6 and showed extracellularly and intracellularly positive staining for SAA, whereas CRP was found exclusively in the cytoplasm of phagocyting white blood cells. Conclusions— Coronary levels of IL-6 and SAA at the site of plaque rupture were increased relative to the systemic circulation, indicating local production of biologically active inflammatory mediators. In contrast, CRP was locally decreased, at least in part by uptake by the phagocyting cells, suggesting a systemic origin of the protein.
New governance framework for NHS research aims to stop fraud
Authors: S. Mayor
Journal: BMJ (2000)

Health research carried out by the NHS in England and Wales must meet new standards designed to protect participants, improve quality, and stop research fraud, according to recommendations proposed in a draft governance framework published by the Department of Health last week.

The framework sets out standards, delivery mechanisms, and monitoring arrangements for all research carried out by the NHS in England and Wales, including joint projects with other partners such as universities, charities, research councils, and pharmaceutical companies.

It brings together for the first time a wide range of existing guidelines to set clear standards for NHS …
Dose-dependent inhibition of stretch-induced arrhythmias by gadolinium in isolated canine ventricles. Evidence for a unique mode of antiarrhythmic action.
Authors: D E Hansen, M Borganelli, G P Stacy, L K Taylor
Journal: Circulation Research (1991)

Transient diastolic dilatation of the isolated canine left ventricle predictably elicits arrhythmias. To test the hypothesis that such arrhythmias may be mediated by sarcolemmal stretch-activated channels, we attempted to inhibit stretch-induced arrhythmias with gadolinium (Gd3+), a potent stretch-activated channel blocker. In experiments with six isolated canine hearts, left ventricular volume was increased for 50 msec during early diastole and then returned to initial volume by a computerized servopump. The stretch volume was adjusted to yield a probability of eliciting a stretch-induced arrhythmia of 95 +/- 2% before treatment with Gd3+. When Gd3+ (1-10 microM) was administered, dose-dependent suppression of stretch-induced arrhythmias was observed. The probability of a stretch-induced arrhythmia was reduced to 13 +/- 10% (p less than 0.05) with 10 microM Gd3+. Washout of Gd3+ completely reversed this effect. Since Gd3+ is known to be a calcium channel antagonist, we compared the effect of Gd3+ on stretch-induced arrhythmias with that of verapamil and nifedipine. These calcium channel blockers produced no demonstrable inhibition of stretch-induced arrhythmias when administered at concentrations (1 microM) that substantially depressed left ventricular pressure development. Thus, our results indirectly implicate stretch-activated channels in the genesis of stretch-induced arrhythmias and provide preliminary evidence for a potential new mode of antiarrhythmic drug action--blockade of stretch-activated channels.
Genotype C hepatitis B virus infection is associated with an increased risk of hepatocellular carcinoma
Authors: H L-Y Chan
Journal: Gut (2004)

Identification of risk factors for the development of hepatocellular carcinoma (HCC) is important for HCC surveillance in chronic hepatitis B virus (HBV) infection. Our aim was to study the independent risk factors and effect of HBV genotypes on HCC development in a prospective longitudinal cohort of chronic hepatitis B patients.Chronic hepatitis B patients recruited since 1997 were prospectively followed up for the development of HCC. HCC was diagnosed by a combination of alpha fetoprotein, imaging, and histology. Liver cirrhosis was defined as ultrasonic features of cirrhosis together with hypersplenism, ascites, varices, and/or encephalopathy.In total, 426 patients were followed up for 1664 person years; median 225 (range 12-295) weeks. Forty nine (11%) patients had underlying clinical liver cirrhosis. A total of 242 (57%) and 179 (42%) patients had HBV genotypes C and B, respectively. Twenty five patients developed HCC in a median follow up of 121 (range 14-236) weeks. The overall incidence of HCC was 1502 cases per 100 000 person years. On multivariate analysis, clinical liver cirrhosis and HBV genotype C infection were independently associated with HCC development, with an adjusted relative risk of 10.24 (95% confidence interval (CI) 4.39-23.89; p<0.001) and 2.84 (95% CI 1.05-7.72; p = 0.040), respectively. Patient age, sex, hepatitis B e antigen (HBeAg) status, alanine aminotransferase (ALT) levels, and basal core promoter mutations did not predict HCC development. Patients infected with HBV genotype C tended to have persistently positive HBeAg or fluctuating HBeAg status and higher ALT levels during the follow up period.Genotype C HBV infection is an independent risk factor for HCC development in addition to liver cirrhosis.