tbuckley/cabot-search huggingface dataset:
Renin is an angiotensin-independent profibrotic mediator: role in pulmonary fibrosis
Authors: E Montes, V Ruiz, M Checa, V Maldonado, J Melendez-Zajgla, M Montaño, R Ordoñez-Razo, J Cisneros, C García-de-Alba, A Pardo, M Selman
Journal: European Respiratory Journal (2011)

The pathogenesis of idiopathic pulmonary fibrosis (IPF) is probably the result of interplay between cytokines/chemokines and growth factors. The renin-angiotensin (Ang) system is involved, although its profibrotic effect is attributed to Ang II. However, recent studies suggest that renin, through a specific receptor, is implicated in fibrogenesis. In this study, the expression of renin and renin receptor was examined in normal and IPF lungs and fibroblasts. Normal human lung fibroblasts were stimulated with renin or transfected with renin small interfering RNA (siRNA), and the expression of transforming growth factor (TGF)-β1 and α-1-type I collagen was analysed. Normal lungs and lung fibroblasts expressed renin, which was strongly upregulated in IPF lungs and fibroblasts (∼10-fold increase; p<0.05). Immunocytochemistry showed intense renin staining in IPF fibroblasts. Renin-stimulated lung fibroblasts displayed an increase in the expression of TGF-β1 (mean ± sd 1.8 × 10(3) ± 0.2 × 10(3) versus 1.2 × 10(3)± 0.3 × 10(3) mRNA copies per 18S ribosomal RNA; p<0.01) and collagen (5.93 × 10(2)± 0.66 × 10(2) versus 3.28 × 10(2) ± 0.5 × 10(2); p<0.01), while knocking down renin expression using siRNA provoked a strong decrease of both molecules. These effects were independent of Ang II, since neither losartan nor captopril decreased these effects. Renin also decreased matrix metalloprotease-1 expression and induced TGF-β1 activation (163 ± 34 versus 110 ± 15 pg active TGF-β1 per mg total protein). These findings highlight the possible role of renin as an Ang II-independent profibrotic factor in lung fibrosis.
Vaccine-Induced Env V1-V2 IgG3 Correlates with Lower HIV-1 Infection Risk and Declines Soon After Vaccination
Authors: Nicole L. Yates, Hua-Xin Liao, Youyi Fong, Allan deCamp, Nathan A. Vandergrift, William T. Williams, S. Munir Alam, Guido Ferrari, Zhi-yong Yang, Kelly E. Seaton, Phillip W. Berman, Michael D. Alpert, David T. Evans, Robert J. O’Connell, Donald Francis, Faruk Sinangil, Carter Lee, Sorachai Nitayaphan, Supachai Rerks-Ngarm, Jaranit Kaewkungwal, Punnee Pitisuttithum, James Tartaglia, Abraham Pinter, Susan Zolla-Pazner, Peter B. Gilbert, Gary J. Nabel, Nelson L. Michael, Jerome H. Kim, David C. Montefiori, Barton F. Haynes, Georgia D. Tomaras
Journal: Science Translational Medicine (2014)

A V1-V2 IgG3 response to HIV correlates with a decreased risk of HIV-1 infection and is one vaccine-induced humoral response that is higher in a clinical trial showing HIV-1 vaccine efficacy compared to a trial showing nonefficacy.
Liver X Receptor Activation Stimulates Iron Export in Human Alternative Macrophages
Authors: Gaël Bories, Sophie Colin, Jonathan Vanhoutte, Bruno Derudas, Corinne Copin, Mélanie Fanchon, Mehdi Daoudi, Loïc Belloy, Stephan Haulon, Christophe Zawadzki, Brigitte Jude, Bart Staels, Giulia Chinetti-Gbaguidi
Journal: Circulation Research (2013)

Rationale: In atherosclerotic plaques, iron preferentially accumulates in macrophages where it can exert pro-oxidant activities. Objective: The objective of this study was, first, to better characterize the iron distribution and metabolism in macrophage subpopulations in human atherosclerotic plaques and, second, to determine whether iron homeostasis is under the control of nuclear receptors, such as the liver X receptors (LXRs). Methods and Results: Here we report that iron depots accumulate in human atherosclerotic plaque areas enriched in CD68 and mannose receptor (MR)-positive (CD68 + MR + ) alternative M2 macrophages. In vitro IL-4 polarization of human monocytes into M2 macrophages also resulted in a gene expression profile and phenotype favoring iron accumulation. However, M2 macrophages on iron exposure acquire a phenotype favoring iron release, through a strong increase in ferroportin expression, illustrated by a more avid oxidation of extracellular low-density lipoprotein by iron-loaded M2 macrophages. In line, in human atherosclerotic plaques, CD68 + MR + macrophages accumulate oxidized lipids, which activate LXRα and LXRβ, resulting in the induction of ABCA1, ABCG1, and apolipoprotein E expression. Moreover, in iron-loaded M2 macrophages, LXR activation induces nuclear factor erythroid 2-like 2 expression, thereby increasing ferroportin expression, which, together with a decrease of hepcidin mRNA levels, promotes iron export. Conclusions: These data identify a role for M2 macrophages in iron handling, a process regulated by LXR activation.
Cost-effectiveness of infliximab versus conventional combination treatment in methotrexate-refractory early rheumatoid arthritis: 2-year results of the register-enriched randomised controlled SWEFOT trial
Authors: Jonas K Eriksson, Johan A Karlsson, Johan Bratt, Ingemar F Petersson, Ronald F van Vollenhoven, Sofia Ernestam, Pierre Geborek, Martin Neovius
Journal: Annals of the Rheumatic Diseases (2014)

Objective To estimate the incremental cost-effectiveness of infliximab versus conventional combination treatment over 21 months in patients with methotrexate-refractory early rheumatoid arthritis. Methods In this multicentre, two-arm, parallel, randomised, active-controlled, open-label trial, rheumatoid arthritis patients with &lt;1 year symptom duration were recruited from 15 rheumatology clinics in Sweden between October 2002 and December 2005. After 3–4 months of methotrexate monotherapy, patients not achieving low disease activity were randomised to addition of infliximab or sulfasalazine+hydroxychloroquine (conventional treatment group). Costs of drugs, healthcare use, and productivity losses were retrieved from nationwide registers, while EuroQol 5-Dimensions utility was collected quarterly. Results Of 487 patients initially enrolled, 128 and 130 were randomised to infliximab and conventional treatment, respectively. The infliximab group accumulated higher drug and healthcare costs (€27 487 vs €10 364; adjusted mean difference €16 956 (95% CI 14 647 to 19 162)), while productivity losses did not differ (€33 804 vs €29 220; €3961 (95% CI −3986 to 11 850)), resulting in higher societal cost compared to the conventional group (€61 291 vs €39 584; €20 916 (95% CI 12 800 to 28 660)). Mean accumulated quality-adjusted life-years (QALYs) did not differ (1.10 vs 1.12; adjusted mean difference favouring infliximab treatment 0.01 (95% CI −0.07 to 0.08)). The incremental cost-effectiveness ratios for the infliximab versus conventional treatment strategy were €2 404 197/QALY from the societal perspective and €1 948 919/QALY from the healthcare perspective. Conclusions In early, methotrexate-refractory rheumatoid arthritis, a treatment strategy commencing with addition of infliximab, as compared to sulfasalazine+hydroxychloroquine, was not cost-effective over 21 months at willingness to pay levels generally considered acceptable. Trial registration number: NCT00764725.
Exhaled breath temperature and nitric oxide in assessing children with and without respiratory disease
Authors: Mario Barreto, Francesco La Penna, Anna Prete, Susanna Bonafoni, Francesco Biagiarelli, Valentina Negro, Salvatore Barberi, Maria Pia Villa
Journal: European Respiratory Journal (2011)

Background: The exhaled breath temperature (EBT) is a potential marker of airway inflammation. Recent data suggests a relationship between EBT and the fractional concentration of exhaled nitric oxide (FENO). Factors influencing EBT and its utility to distinguish subjects with respiratory disease are scarcely known.

Aims: To compare EBT and FENO in patients with asthma, rhinitis and healthy children.

Methods: In 50 subjects aged 10.3±2.8 yr (30 males), 26 with asthma, 11 with rhinitis and 13 healthy we measured the EBT plateau (EBTp, °C), FENO, spirometry at baseline and after inhaled salbutamol, skin prick test for common allergens, questionnaires and scores for respiratory symptoms. Post-salbutamol changes (D prefix) were calculated.

Results: EBTp and FENO correlated with age (r= 0.61 and r=0.34, p<0.02); FENO correlated also with lung function (e.g. with FEF25-75%: r=-0.60, p<0.001; DFEV1: r=0.58, p<0.001). EBTp correlated with FENO only in asthmatic subjects (r=0.40, p<0.05). All children with asthma and 9/11 with rhinitis had positive skin prick tests. Both EBTp and FENO were higher in asthmatic patients with reported moderate-to-severe dyspnea in the past 4 weeks than in asthmatic patients without or mild dyspnea and healthy children (EBTp: 32.4±1.6 vs 30.2±2.8 vs 30.0±3.0, p<0.05). FENO levels were also higher in symptomatic patients with asthma than in patients with rhinitis (48.4 ppb, 95% CI: 34.7–67.5 vs 11.0 ppb, 95% CI: 9.0–13.4, p<0.001). EBTp values were not influenced by current inhaled corticosteroid therapy.

Conclusion: EBTp and FENO are influenced by subjects' age. Both markers are useful to distinguish patients with poor asthma control from healthy patients.
Topical Therapy with Nadifloxacin Cream and Prednicarbat Cream Improves Acneiform Eruptions Caused by the EGFR-Inhibitor Cetuximab
Authors: A WOLLENBERG, K KATZER, J TIETZE, E KLEIN, J KROTH, V HEINEMAN, T RUZICKA
Journal: Journal of Allergy and Clinical Immunology (2008)
Reducing Amputation Rates in Patients With Diabetes at a Military Medical Center
Authors: Vickie R. Driver, Jeff Madsen, Russell A. Goodman
Journal: Diabetes Care (2005)

To describe and evaluate the Limb Preservation Service (LPS), a multidisciplinary, state-of-the-art, foot care clinic for patients with diabetes at Madigan Army Medical Center (MAMC). Evaluation criteria include the overall incidence of lower-extremity amputation (LEA) and the distribution of the anatomic level of amputation between 1999 and 2003.This is a retrospective study of the incidence and types of LEAs performed in patients with diabetes at MAMC. Patients with diagnosed diabetes and LEA procedures were identified by ICD-9-Clinical Modification (CM) codes. Hospital and clinic characteristics that are integral to the success of the program are described.The number of patients at MAMC with diagnosed diabetes increased 48% from 1999 to 2003; however, the number of LEAs decreased 82% from 33 in 1999 to 9 in 2003. Amputations of the foot, ankle, and toe comprise 71% of amputations among patients with diabetes.The results of this study provide evidence of the value of a focused multidisciplinary foot care program for patients with diabetes. Associations between the creation of the LPS and LEA rates are discussed.
Experience with tretinoin therapy in temperate regions
Authors: R. Caputo, M. Monti, C. Rigoni, S. Pinelli, S. Motta, M. Barbareschi
Journal: British Journal of Dermatology (1992)

In a previously reported study on the anti-photoageing effects of topical tretinoin, the following regimen produced good patient compliance: 0.01% for 1 month, 0.025% for 1 month; and 0.05% for 4 months. The majority of patients (60/89) enrolled in the initial study continued to apply the cream to the face, and a further 140 patients were enrolled for a long-term study (mean duration 2 years). The prolonged study showed that 91.4% of patients used tretinoin in an attempt to slow down skin aging, and 8.6% sought subjective skin benefits. Of the 163 patients who completed the study, 58.8% sought an improvement of wrinkles, 30.1% skin trophism and 14.7% reduced pigmentation. The product was used throughout the year by 66.9% of patients, but 8.0% stopped using it during the summer. A daytime moisturizing cream was required by 77.9% of patients, and 82.8% used a sunscreen in the summer. Tretinoin was applied to other areas of the body by 63.8% of patients.
Effect of closed endotracheal suction in high-frequency ventilated premature infants measured with electrical impedance tomography
Authors: Mariëtte B. van Veenendaal, Martijn Miedema, Frans H. C. de Jongh, Johanna H. van der Lee, Inez Frerichs, Anton H. van Kaam
Journal: Intensive Care Medicine (2009)

To determine the global and regional changes in lung volume during and after closed endotracheal tube (ETT) suction in high-frequency ventilated preterm infants with respiratory distress syndrome (RDS).Prospective observational clinical study.Neonatal intensive care unit.Eleven non-muscle relaxed preterm infants with RDS ventilated with open lung high-frequency ventilation (HFV).Closed ETT suction.Changes in global and regional lung volume were measured with electrical impedance tomography. ETT suction resulted in an acute loss of lung volume followed by spontaneous recovery with a median residual loss of 3.3% of the maximum volume loss. The median stabilization time was 8 s. At the regional level, the lung volume changes during and after ETT suction were heterogeneous in nature.Closed ETT suction causes an acute, transient and heterogeneous loss of lung volume in premature infants with RDS treated with open lung HFV.
<i>In vitro</i> and <i>In vivo</i> Radiosensitization Induced by the Ribonucleotide Reductase Inhibitor Triapine (3-Aminopyridine-2-Carboxaldehyde-Thiosemicarbazone)
Authors: Christopher A. Barker, William E. Burgan, Donna J. Carter, David Cerna, David Gius, Melinda G. Hollingshead, Kevin Camphausen, Philip J. Tofilon
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Because ribonucleotide reductase (RR) plays a role in DNA repair, it may serve as a molecular target for radiosensitization. Unlike previously investigated RR inhibitors, Triapine potently inhibits both RR holoenzymes. Therefore, the effects of Triapine on tumor cell radiosensitivity were investigated. Experimental Design: The effects of Triapine on the in vitro radiosensitivity of three human tumor cell lines and one normal cell line were evaluated using a clonogenic assay. Growth delay was used to evaluate the effects of Triapine on in vivo tumor radiosensitivity. The levels of the RR subunits were determined using immunoblot analysis and DNA damage and repair were evaluated using γH2AX foci. Results: Exposure of the tumor cell lines to Triapine before or immediately after irradiation resulted in an increase in radiosensitivity. In contrast, Triapine enhanced the radiosensitivity of the normal fibroblast cell line only when the exposure was before irradiation. There were no consistent differences between cell lines with respect to the expression of the RR subunits. Whereas Triapine had no effect on radiation-induced γH2AX foci at 1 hour, the number of γH2AX foci per cell was significantly greater in the Triapine-treated cells at 24 hours after irradiation, suggesting the presence of unrepaired DNA damage. Triapine administration to mice bearing tumor xenografts immediately after irradiation resulted in a greater than additive increase in radiation-induced tumor growth delay. Conclusions: These results indicate that Triapine can enhance tumor cell radiosensitivity in vitro and in vivo and suggest that this effect involves an inhibition of DNA repair.
An outbreak of neurological autoimmunity with polyradiculoneuropathy in workers exposed to aerosolised porcine neural tissue: a descriptive study
Authors: Daniel H Lachance, Vanda A Lennon, Sean J Pittock, Jennifer A Tracy, Karl N Krecke, Kimberly K Amrami, Eric M Poeschla, Robert Orenstein, Bernd W Scheithauer, James J Sejvar, Stacy Holzbauer, Aaron S DeVries, P James B Dyck
Journal: The Lancet Neurology (2009)
Randomized Trial Comparing Cyclophosphamide, Epirubicin, and Fluorouracil With Cyclophosphamide, Methotrexate, and Fluorouracil in Premenopausal Women With Node-Positive Breast Cancer: Update of National Cancer Institute of Canada Clinical Trials Group Trial MA5
Authors: Mark N. Levine, Kathleen I. Pritchard, Vivien H.C. Bramwell, Lois E. Shepherd, Dongsheng Tu, Nancy Paul
Journal: Journal of Clinical Oncology (2005)

Purpose Certain anthracycline-containing adjuvant chemotherapy regimens are associated with improved relapse-free survival (RFS) and overall survival (OS) compared with the classic regimen of cyclophosphamide, methotrexate, and fluorouracil in women with early-stage breast cancer. Patients and Methods Between 1989 and 1993, 710 pre- and perimenopausal women with axillary node–positive breast cancer were randomly assigned to either cyclophosphamide 75 mg/m 2 orally days 1 through 14, epirubicin 60 mg/m 2 intravenously days 1 and 8, and fluorouracil 500 mg/m 2 intravenously days 1 and 8 (CEF) or CMF (cyclophosphamide 100 mg/m 2 orally days 1 through 14, methotrexate 40 mg/m 2 intravenously days 1 and 8, and fluorouracil 600 mg/m 2 intravenously days 1 and 8). On the basis of follow-up to May 1997 (median follow-up time, 59 months), there was a statistically significant improvement in RFS and OS for CEF compared with CMF. Results The trial results are now updated, with a median follow-up of 10 years for live patients. The 10-year RFS is 52% for patients who received CEF compared with 45% for CMF patients (hazard ratio [HR] for CMF v CEF = 1.31; stratified log-rank, P = .007). The 10-year OS for patients who received CEF and CMF are 62% and 58%, respectively (HR for CMF v CEF = 1.18; stratified log-rank, P = .085). The rates of acute leukemia have not changed since the original report, whereas the rates of congestive heart failure are slightly higher but acceptable (four patients [1.1%] in the CEF group v one patient [0.3%] in the CMF group). Conclusion The previously demonstrated benefit of CEF compared with CMF adjuvant chemotherapy is maintained with longer follow-up in the MA5 trial.
1223 NO EARLY VIROLOGIC BREAKTHROUGH OBSERVED WITH THE HCV NS3 PROTEASE INHIBITOR BMS-650032 IN MULTIPLE DOSE MONOTHERAPY STUDIES AND PHASE 2A COMBINATION STUDIES WITH PEGIFNα/RBV
Authors: F. McPhee, A. Sheaffer, F. Yu, M. Lee, S. Chaniewski, P. Falk, C. Pasquinelli, C. Llasamo, E. Hughes, D. Hernandez
Journal: Journal of Hepatology (2011)
Angiopoietin-2 sensitizes endothelial cells to TNF-α and has a crucial role in the induction of inflammation
Authors: Ulrike Fiedler, Yvonne Reiss, Marion Scharpfenecker, Verena Grunow, Stefanie Koidl, Gavin Thurston, Nicholas W Gale, Martin Witzenrath, Simone Rosseau, Norbert Suttorp, Astrid Sobke, Matthias Herrmann, Klaus T Preissner, Peter Vajkoczy, Hellmut G Augustin
Journal: Nature Medicine (2006)
Secondary hematological malignancies associated with temozolomide in patients with glioma
Authors: H. Momota, Y. Narita, Y. Miyakita, S. Shibui
Journal: Neuro-Oncology (2013)

BackgroundThe alkylating agent temozolomide (TMZ) is widely used for the treatment of gliomas. Although reports of treatment-related myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL) associated with TMZ are accumulating, it remains unclear whether TMZ has the same leukemogenic potential as other alkylating agents.
Effect of tailored practice and patient care plans on secondary prevention of heart disease in general practice: cluster randomised controlled trial
Authors: A W Murphy, M E Cupples, S M Smith, M Byrne, M C Byrne, J Newell
Journal: BMJ (2009)

<b>Objective</b> To test the effectiveness of a complex intervention designed, within a theoretical framework, to improve outcomes for patients with coronary heart disease. <b>Design</b> Cluster randomised controlled multicentre trial. <b>Setting</b> General practices in Northern Ireland and the Republic of Ireland, regions with different healthcare systems. <b>Participants</b> 903 patients with established coronary heart disease registered with one of 48 practices. <b>Intervention</b> Tailored care plans for practices (practice based training in prescribing and behaviour change, administrative support, quarterly newsletter), and tailored care plans for patients (motivational interviewing, goal identification, and target setting for lifestyle change) with reviews every four months at the practices. Control practices provided usual care. <b>Main outcome measures</b> The proportion of patients at 18 month follow-up above target levels for blood pressure and total cholesterol concentration, and those admitted to hospital, and changes in physical and mental health status (SF-12). <b>Results</b> At baseline the numbers (proportions) of patients above the recommended limits were: systolic blood pressure greater than 140 mm Hg (305/899; 33.9%, 95% confidence interval 30.8% to 33.9%), diastolic blood pressure greater than 90 mm Hg (111/901; 12.3%, 10.2% to 14.5%), and total cholesterol concentration greater than 5 mmol/l (188/860; 20.8%, 19.1% to 24.6%). At the 18 month follow-up there were no significant differences between intervention and control groups in the numbers (proportions) of patients above the recommended limits: systolic blood pressure, intervention 98/360 (27.2%) <i>v</i> control, 133/405 (32.8%), odds ratio 1.51 (95% confidence interval 0.99 to 2.30; P=0.06); diastolic blood pressure, intervention 32/360 (8.9%) <i>v</i> control, 40/405 (9.9%), 1.40 (0.75 to 2.64; P=0.29); and total cholesterol concentration, intervention 52/342 (15.2%) <i>v</i> control, 64/391 (16.4%), 1.13 (0.63 to 2.03; P=0.65). The number of patients admitted to hospital over the 18 month study period significantly decreased in the intervention group compared with the control group: 107/415 (25.8%) <i>v</i> 148/435 (34.0%), 1.56 (1.53 to 2.60; P=0.03). <b>Conclusions</b> Admissions to hospital were significantly reduced after an intensive 18 month intervention to improve outcomes for patients with coronary heart disease, but no other clinical benefits were shown, possibly because of a ceiling effect related to improved management of the disease. <b>Trial registration</b> Current Controlled Trials ISRCTN24081411.
International Consensus Report Urges Sweeping Reform in Asthma Treatment
Authors: Teri Randall
Journal: JAMA (1992)

AN INTERNATIONAL panel of  experts is advising physicians to adopt a sweeping philosophical change in the way they manage asthma. Treat  not as an episodic, bronchospastic disorder, they suggest, but as a chronic, persistent disease with inflammation at its core.  That is the word from the International Asthma Management Project, a working group of 18 physicians and scientists convened by the National Heart, Lung, and Blood Institute, Bethesda, Md, in their now-released report on the diagnosis and management of asthma.  In what is termed an international consensus, the report recommends regular use of anti-inflammatory drugs, preferably inhaled corticosteroids, as first-line therapy for anything more than occasional mild asthma. β 2 -Agonist bronchodilators, commonly used in the United States as regularly scheduled, first-line therapy, are endorsed only for the pretreatment of exercise-induced  and for the symptomatic relief of acute exacerbations, or asthma attacks, when anti-inflammatory therapy is insufficient.
Physical inactivity remains the greatest public health problem of the 21st century: evidence, improved methods and solutions using the ‘7 investments that work’ as a framework
Authors: Stewart G Trost, Steven N Blair, Karim M Khan
Journal: British Journal of Sports Medicine (2014)

In 2009, BJSM's first editorial argued that ‘Physical inactivity is the greatest public health problem of the 21st century’.1 The data supporting that claim have not yet been challenged. Now, 5 years after BJSM published its first dedicated ‘Physical Activity is Medicine’ theme issue (http://bjsm.bmj.com/content/43/1.toc) we are pleased to highlight 23 new contributions from six countries. This issue contains an analysis of the cost of physical inactivity from the US Centre for Diseases Control.2 We also report the cost-effectiveness of one particular physical activity intervention for adults.3