tbuckley/cabot-search huggingface dataset:
Access to heart surgery for smokers: Authors' reply
Authors: M J Underwood, J S Bailey
Journal: BMJ (1993)

He and many others might never have taken to smoking if there had not been a war.Nothing was known about a link with any disease then.Not even the medical profession knew-except the first few who suspected a link with lung cancer, and even that was not clear for a long time afterwards.All these survivors of the war are now at an age when they may need bypass surgery.They smoked through no fault of their own, and nobody had knowledge of possible consequences.They were encouraged to smoke and given easy access to cigarettes.They gave five years of their young lives to the defence of Britain.Are our surgeons, most of whom will be much younger, and who can have no personal experience of those days, now to deny these men treatment for physical conditions possibly engendered by their years of smoking?I hope not.
Dietary fibre intake and risk of cardiovascular disease: systematic review and meta-analysis
Authors: D. E. Threapleton, D. C. Greenwood, C. E. L. Evans, C. L. Cleghorn, C. Nykjaer, C. Woodhead, J. E. Cade, C. P. Gale, V. J. Burley
Journal: BMJ (2013)

<b>Objective</b> To investigate dietary fibre intake and any potential dose-response association with coronary heart disease and cardiovascular disease. <b>Design</b> Systematic review of available literature and dose-response meta-analysis of cohort studies using random effects models. <b>Data sources</b> The Cochrane Library, Medline, Medline in-process, Embase, CAB Abstracts, ISI Web of Science, BIOSIS, and hand searching. <b>Eligibility criteria for studies</b> Prospective studies reporting associations between fibre intake and coronary heart disease or cardiovascular disease, with a minimum follow-up of three years and published in English between 1 January 1990 and 6 August 2013. <b>Results</b> 22 cohort study publications met inclusion criteria and reported total dietary fibre intake, fibre subtypes, or fibre from food sources and primary events of cardiovascular disease or coronary heart disease. Total dietary fibre intake was inversely associated with risk of cardiovascular disease (risk ratio 0.91 per 7 g/day (95% confidence intervals 0.88 to 0.94)) and coronary heart disease (0.91 (0.87 to 0.94)). There was evidence of some heterogeneity between pooled studies for cardiovascular disease (I<sup>2</sup>=45% (0% to 74%)) and coronary heart disease (I<sup>2</sup>=33% (0% to 66%)). Insoluble fibre and fibre from cereal and vegetable sources were inversely associated with risk of coronary heart disease and cardiovascular disease. Fruit fibre intake was inversely associated with risk of cardiovascular disease. <b>Conclusions</b> Greater dietary fibre intake is associated with a lower risk of both cardiovascular disease and coronary heart disease. Findings are aligned with general recommendations to increase fibre intake. The differing strengths of association by fibre type or source highlight the need for a better understanding of the mode of action of fibre components.
The role of cardiac power and systemic vascular resistance in the pathophysiology and diagnosis of patients with acute congestive heart failure
Authors: Gad Cotter, Yaron Moshkovitz, Edo Kaluski, Olga Milo, Ylia Nobikov, Adam Schneeweiss, Ricardo Krakover, Zvi Vered
Journal: Journal of the American College of Cardiology (2003)
Road tunnel air pollution induces bronchoalveolar inflammation in healthy subjects
Authors: B-M. Larsson, M. Sehlstedt, J. Grunewald, C. M. Sköld, A. Lundin, A. Blomberg, T. Sandström, A. Eklund, M. Svartengren
Journal: European Respiratory Journal (2007)

Traffic-related air pollution is associated with adverse respiratory effects. The aim of the present study was to investigate whether exposure to air pollution in a road tunnel causes airway inflammatory and blood coagulation responses. A total of 16 healthy subjects underwent bronchoscopy with bronchial mucosal biopsies and bronchoalveolar lavage (BAL) on two occasions, in random order: once at 14 h after a 2-h exposure to air pollution in a busy road tunnel, and once after a control day with subjects exposed to urban air during normal activities. Peripheral blood was sampled prior to bronchoscopy. The road tunnel exposures included particulate matter with a 50% cut-off aerodynamic diameter of 2.5 μm, particulate matter with a 50% cut-off aerodynamic diameter of 10 μm and nitrogen dioxide which had median concentrations of 64, 176 and 230 µg·m −3 , respectively. Significantly higher numbers of BAL fluid total cell number, lymphocytes and alveolar macrophages were present after road tunnel exposure versus control. Significantly higher nuclear expression of the transcription factor component c-Jun was found in the bronchial epithelium after exposure. No upregulation of adhesion molecules or cellular infiltration was present and blood coagulation factors were unaffected. In conclusion, exposure of healthy subjects to traffic-related air pollution resulted in a lower airway inflammatory response with cell migration, together with signs of an initiated signal transduction in the bronchial epithelium.
Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis
Authors: John D Rioux, Ramnik J Xavier, Kent D Taylor, Mark S Silverberg, Philippe Goyette, Alan Huett, Todd Green, Petric Kuballa, M Michael Barmada, Lisa Wu Datta, Yin Yao Shugart, Anne M Griffiths, Stephan R Targan, Andrew F Ippoliti, Edmond-Jean Bernard, Ling Mei, Dan L Nicolae, Miguel Regueiro, L Philip Schumm, A Hillary Steinhart, Jerome I Rotter, Richard H Duerr, Judy H Cho, Mark J Daly, Steven R Brant
Journal: Nature Genetics (2007)
The Outcome of Bulimia Nervosa: Findings From One-Quarter Century of Research
Authors: Hans-Christoph Steinhausen, Sandy Weber
Journal: American Journal of Psychiatry (2009)

Objective: The present review addresses the outcome of bulimia nervosa, effect variables, and prognostic factors. Method: A total of 79 study series covering 5,653 patients suffering from bulimia nervosa were analyzed with regard to recovery, improvement, chronicity, crossover to another eating disorder, mortality, and comorbid psychiatric disorders at outcome. Forty-nine studies dealt with prognosis only. Final analyses on prognostic factors were based on 4,639 patients. Results: Joint analyses of data were hampered by a lack of standardized outcome criteria. There were large variations in the outcome parameters across studies. Based on 27 studies with three outcome criteria (recovery, improvement, chronicity), close to 45% of the patients on average showed full recovery of bulimia nervosa, whereas 27% on average improved considerably and nearly 23% on average had a chronic protracted course. Crossover to another eating disorder at the follow-up evaluation in 23 studies amounted to a mean of 22.5%. The crude mortality rate was 0.32%, and other psychiatric disorders at outcome were very common. Among various variables of effect, duration of follow-up had the largest effect size. The data suggest a curvilinear course, with highest recovery rates between 4 and 9 years of follow-up evaluation and reverse peaks for both improvement and chronicity, including rates of crossover to another eating disorder, before 4 years and after 10 years of follow-up evaluation. For most prognostic factors, there was only conflicting evidence. Conclusions: One-quarter of a century of specific research in bulimia nervosa shows that the disorder still has an unsatisfactory outcome in many patients. More refined interventions may contribute to more favorable outcomes in the future.
Velocity of the creatine kinase reaction decreases in postischemic myocardium: a 31P-NMR magnetization transfer study of the isolated ferret heart.
Authors: S Neubauer, B L Hamman, S B Perry, J A Bittl, J S Ingwall
Journal: Circulation Research (1988)

Recovery of postischemic function may be limited by energy synthesis by mitochondria, energy transfer via the creatine kinase reaction, or energy utilization at myofibrils. To identify the limiting step, we defined the relations among oxygen consumption, creatine kinase reaction velocity and cardiac performance in myocardium reperfused following mild, moderate, and severe ischemia. Isolated isovolumic ferret hearts were perfused with Krebs-Henseleit buffer at 37 degrees C. After 30 minutes of control, hearts were made ischemic for 20, 40, or 60 minutes and reperfused for 40 minutes. During preischemia, cardiac performance (estimated as the rate-pressure product), was 14.8 x 10(3) mm Hg/min, oxygen consumption was 16.7 mumol/min/g dry weight, and creatine kinase reaction velocity measured by 31P-nuclear magnetic resonance saturation transfer was 12.7 mM/sec. For hearts reperfused after 20, 40, or 60 minutes of ischemia, rate-pressure product was 11.5, 6.5, and 1.1 x 10(3) mm Hg/min; oxygen consumption was 13.5, 14.2, and 6.9 mumol/min/g dry weight; and creatine kinase reaction velocity was 9.6, 5.0, and 2.0 mM/sec, respectively. Thus, with increasing severity of insult, creatine kinase reaction velocity decreased monotonically with performance (r = 0.99). Changes in creatine kinase reaction velocity were predicted from the creatine kinase rate equation (r = 0.99; predicted vs. measured velocity) and can therefore be explained by changes in substrate concentration. Oxygen consumption did not correlate with performance or creatine kinase velocity, consistent with abnormalities in mitochondrial energy production. In all cases, creatine kinase reaction velocity was an order of magnitude faster than the maximal rate of ATP synthesis estimated by oxygen consumption. We conclude that, in postischemic myocardium, creatine kinase reaction velocity decreases in proportion to performance, but high-energy phosphate transfer does not limit availability of high-energy phosphate for contraction.
Chemoselection As a Strategy for Organ Preservation in Advanced Oropharynx Cancer: Response and Survival Positively Associated With HPV16 Copy Number
Authors: Francis P. Worden, Bhavna Kumar, Julia S. Lee, Gregory T. Wolf, Kitrina G. Cordell, Jeremy M.G. Taylor, Susan G. Urba, Avraham Eisbruch, Theodoros N. Teknos, Douglas B. Chepeha, Mark E. Prince, Christina I. Tsien, Nisha J. D’Silva, Kun Yang, David M. Kurnit, Heidi L. Mason, Tamara H. Miller, Nancy E. Wallace, Carol R. Bradford, Thomas E. Carey
Journal: Journal of Clinical Oncology (2008)

Purpose To test induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CRT) or surgery/radiotherapy (RT) for advanced oropharyngeal cancer and to assess the effect of human papilloma virus (HPV) on response and outcome. Patients and Methods Sixty-six patients (51 male; 15 female) with stage III to IV squamous cell carcinoma of the oropharynx (SCCOP) were treated with one cycle of cisplatin (100 mg/m 2 ) or carboplatin (AUC 6) and with fluorouracil (1,000 mg/m 2 /d for 5 days) to select candidates for CRT. Those achieving a greater than 50% response at the primary tumor received CRT (70 Gy; 35 fractions with concurrent cisplatin 100 mg/m 2 or carboplatin (AUC 6) every 21 days for three cycles). Adjuvant paclitaxel was given to patients who were complete histologic responders. Patients with a response of 50% or less underwent definitive surgery and postoperative radiation. Pretreatment biopsies from 42 patients were tested for high-risk HPV. Results Fifty-four of 66 patients (81%) had a greater than 50% response after IC. Of these, 53 (98%) received CRT, and 49 (92%) obtained complete histologic response with a 73.4% (47 of 64) rate of organ preservation. The 4-year overall survival (OS) was 70.4%, and the disease-specific survival (DSS) was 75.8% (median follow-up, 64.1 months). HPV16, found in 27 of 42 (64.3%) biopsies, was associated with younger age (median, 55 v 63 years; P = .016), sex (22 of 30 males [73.3%] and five of 12 females [41.7%]; P = .08), and nonsmoking status (P = .037). HPV titer was significantly associated with IC response (P = .001), CRT response (P = .005), OS (P = .007), and DSS (P = .008). Conclusion Although the numbers in this study are small, IC followed by CRT is an effective treatment for SCCOP, especially in patients with HPV-positive tumors; however, for patients who do not respond to treatment, alternative treatments must be developed.
Influence of Type 2 Diabetes on Brain Volumes and Changes in Brain Volumes
Authors: Mark A. Espeland, R. Nick Bryan, Joseph S. Goveas, Jennifer G. Robinson, Mustafa S. Siddiqui, Simin Liu, Patricia E. Hogan, Ramon Casanova, Laura H. Coker, Kristine Yaffe, Kamal Masaki, Rebecca Rossom, Susan M. Resnick
Journal: Diabetes Care (2012)

To study how type 2 diabetes adversely affects brain volumes, changes in volume, and cognitive function.Regional brain volumes and ischemic lesion volumes in 1,366 women, aged 72-89 years, were measured with structural brain magnetic resonance imaging (MRI). Repeat scans were collected an average of 4.7 years later in 698 women. Cross-sectional differences and changes with time between women with and without diabetes were compared. Relationships that cognitive function test scores had with these measures and diabetes were examined.The 145 women with diabetes (10.6%) at the first MRI had smaller total brain volumes (0.6% less; P = 0.05) and smaller gray matter volumes (1.5% less; P = 0.01) but not white matter volumes, both overall and within major lobes. They also had larger ischemic lesion volumes (21.8% greater; P = 0.02), both overall and in gray matter (27.5% greater; P = 0.06), in white matter (18.8% greater; P = 0.02), and across major lobes. Overall, women with diabetes had slightly (nonsignificant) greater loss of total brain volumes (3.02 cc; P = 0.11) and significant increases in total ischemic lesion volumes (9.7% more; P = 0.05) with time relative to those without diabetes. Diabetes was associated with lower scores in global cognitive function and its subdomains. These relative deficits were only partially accounted for by brain volumes and risk factors for cognitive deficits.Diabetes is associated with smaller brain volumes in gray but not white matter and increasing ischemic lesion volumes throughout the brain. These markers are associated with but do not fully account for diabetes-related deficits in cognitive function.
Cannabinoid Receptor Activation Induces Apoptosis through Tumor Necrosis Factor α–Mediated Ceramide <i>De novo</i> Synthesis in Colon Cancer Cells
Authors: Fabio Cianchi, Laura Papucci, Nicola Schiavone, Matteo Lulli, Lucia Magnelli, Maria Cristina Vinci, Luca Messerini, Clementina Manera, Elisa Ronconi, Paola Romagnani, Martino Donnini, Giuliano Perigli, Giacomo Trallori, Elisabetta Tanganelli, Sergio Capaccioli, Emanuela Masini
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Cannabinoids have been recently proposed as a new family of potential antitumor agents. The present study was undertaken to investigate the expression of the two cannabinoid receptors, CB1 and CB2, in colorectal cancer and to provide new insight into the molecular pathways underlying the apoptotic activity induced by their activation. Experimental Design: Cannabinoid receptor expression was investigated in both human cancer specimens and in the DLD-1 and HT29 colon cancer cell lines. The effects of the CB1 agonist arachinodyl-2'-chloroethylamide and the CB2 agonist N-cyclopentyl-7-methyl-1-(2-morpholin-4-ylethyl)-1,8-naphthyridin-4(1H)-on-3-carboxamide (CB13) on tumor cell apoptosis and ceramide and tumor necrosis factor (TNF)-α production were evaluated. The knockdown of TNF-α mRNA was obtained with the use of selective small interfering RNA. Results: We show that the CB1 receptor was mainly expressed in human normal colonic epithelium whereas tumor tissue was strongly positive for the CB2 receptor. The activation of the CB1 and, more efficiently, of the CB2 receptors induced apoptosis and increased ceramide levels in the DLD-1 and HT29 cells. Apoptosis was prevented by the pharmacologic inhibition of ceramide de novo synthesis. The CB2 agonist CB13 also reduced the growth of DLD-1 cells in a mouse model of colon cancer. The knockdown of TNF-α mRNA abrogated the ceramide increase and, therefore, the apoptotic effect induced by cannabinoid receptor activation. Conclusions: The present study shows that either CB1 or CB2 receptor activation induces apoptosis through ceramide de novo synthesis in colon cancer cells. Our data unveiled, for the first time, that TNF-α acts as a link between cannabinoid receptor activation and ceramide production.
Left Ventricular Mass in Patients With Type 2 Diabetes Is Independently Associated With Central but not Peripheral Pulse Pressure
Authors: James E. Sharman, Zhi Y. Fang, Brian Haluska, Michael Stowasser, Johannes B. Prins, Thomas H. Marwick
Journal: Diabetes Care (2005)

An increase in left ventricular mass (LVM) occurs in the presence of type 2 diabetes, apparently independent of hypertension (1), but the determinants of this process are unknown. Brachial blood pressure is not representative of that at the ascending aorta (2) because the pressure wave is amplified from central to peripheral arteries. Central blood pressure is probably more clinically important since local pulsatile pressure determines adverse arterial and myocardial remodeling (3,4). Thus, an inaccurate assessment of the contribution of arterial blood pressure to LVM may occur if only brachial blood pressure is taken into consideration. In this study we sought the contribution of central blood pressure (and other interactive factors known to affect wave reflection, e.g., glycemic control and total arterial compliance) to LVM in patients with type 2 diabetes.
Nitric Oxide Scavenging by Red Blood Cell Microparticles and Cell-Free Hemoglobin as a Mechanism for the Red Cell Storage Lesion
Authors: Chenell Donadee, Nicolaas J.H. Raat, Tamir Kanias, Jesús Tejero, Janet S. Lee, Eric E. Kelley, Xuejun Zhao, Chen Liu, Hannah Reynolds, Ivan Azarov, Sheila Frizzell, E. Michael Meyer, Albert D. Donnenberg, Lirong Qu, Darrel Triulzi, Daniel B. Kim-Shapiro, Mark T. Gladwin
Journal: Circulation (2011)

Background— Intravascular red cell hemolysis impairs nitric oxide (NO)–redox homeostasis, producing endothelial dysfunction, platelet activation, and vasculopathy. Red blood cell storage under standard conditions results in reduced integrity of the erythrocyte membrane, with formation of exocytic microvesicles or microparticles and hemolysis, which we hypothesized could impair vascular function and contribute to the putative storage lesion of banked blood. Methods and Results— We now find that storage of human red blood cells under standard blood banking conditions results in the accumulation of cell-free and microparticle-encapsulated hemoglobin, which, despite 39 days of storage, remains in the reduced ferrous oxyhemoglobin redox state and stoichiometrically reacts with and scavenges the vasodilator NO. Using stopped-flow spectroscopy and laser-triggered NO release from a caged NO compound, we found that both free hemoglobin and microparticles react with NO about 1000 times faster than with intact erythrocytes. In complementary in vivo studies, we show that hemoglobin, even at concentrations below 10 μmol/L (in heme), produces potent vasoconstriction when infused into the rat circulation, whereas controlled infusions of methemoglobin and cyanomethemoglobin, which do not consume NO, have substantially reduced vasoconstrictor effects. Infusion of the plasma from stored human red blood cell units into the rat circulation produces significant vasoconstriction related to the magnitude of storage-related hemolysis. Conclusions— The results of these studies suggest new mechanisms for endothelial injury and impaired vascular function associated with the most fundamental of storage lesions, hemolysis.
Net inflammatory capacity of human septic shock plasma evaluated by a monocyte-based target cell assay: identification of interleukin-10 as a major functional deactivator of human monocytes.
Authors: P Brandtzaeg, L Osnes, R Ovstebø, G B Joø, A B Westvik, P Kierulf
Journal: The Journal of Experimental Medicine (1996)

We have developed a functional assay to study the inflammatory capacity of plasma collected from patients with severe gram-negative septic shock. In this assay, elutriation-purified, cryo-preserved human monocytes from one healthy donor are combined with plasma from patients with severe persistent septic shock for 5 h. Subsequently, the plasma is removed, medium added, and procoagulant activity (PCA) and secretion of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) measured after 18-h incubation. Plasma from 10 patients (6 died) infected with Neisseria meningitidis previously shown to contain high levels of native lipopolysaccharide (LPS) (median 2,700 pg/ml), TNF-alpha, IL-6, IL-8, and complement activation products, had a low net spontaneous inflammatory capacity on the monocytes. The median levels of PCA, TNF-alpha, and IL-6 were 5, 0, and 4%, respectively, of the monocyte activities induced by normal plasma boosted with purified N. meningitidis (Nm)-LPS (2,500 pg/ml; net LPS-boosted capacity, 100%). The levels of PCA, TNF-alpha, and IL-6 obtained with plasma from shock patients were not different from those induced by plasma from 10 meningococcal patients without shock or with plasma from healthy persons. Boosting shock plasma with 2,500 pg/ml Nm-LPS had little effect on the monocyte activities since the median values of PCA, TNF-alpha, and IL-6 revealed a minimal increase from 5, 0, and 4% to 9, 2, and 6%, respectively. The shock plasmas revealed a strong LPS-inhibitory capacity that was largely absent in plasmas from 10 meningococcal patients without shock since the median levels of PCA, TNF-alpha, and IL-6 increased from 5, 0, and 0% to 135, 51, and 73%, respectively, after boosting with 2,500 pg/ml Nm-LPS. The LPS-inhibitory capacity was closely associated with the levels of IL-10. The median levels of IL-10 were 19,000 pg/ml in nine shock patients vs. 22 pg/ml in nine nonshock patients with systemic meningococcal disease. Removal of native IL-10 by immunoprecipitation restored the capacity of plasmas to induce monocyte activation either by native LPS or by boosting with Nm-LPS. IL-4 and TGF-beta were not detected in shock plasmas. In 24 patients with detectable meningococcal LPS ( > 10 pg/ml, 0.1 endotoxin units/ml), the levels of IL-10 were correlated to the levels of LPS (r = 0.79, P < 0.001). IL-10 declined from initiation of antibiotic therapy and paralleled the levels of native LPS. Decreasing levels of IL-10 in serially collected shock plasmas were directly related to increasing monocyte responsiveness after Nm-LPS boosting. These results suggest that IL-10 plays a major role in containing activation of monocytes and possibly other LPS-responsive cells during overwhelming meningococcemia.