tbuckley/cabot-search huggingface dataset:
Longitudinal analysis of the effects of smoking onset and cessation on pulmonary function.
Authors: D L Sherrill, C J Holberg, P L Enright, M D Lebowitz, B Burrows
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

We examined the effects of smoking onset and cessation on FEV1 in participants in the Tucson Epidemiological Study of Airways Obstructive Disease 18 yr of age or older who reported a change in smoking habits during 17 yr of follow-up. Subjects were classified as "new quitters" (n = 288) and "new starters" (n = 45) at each survey on the basis of questionnaire responses concerning current smoking habits. The pulmonary function data were analyzed using a mixed longitudinal or random effects model (REM). We compared FEV1 before and after changing smoking habits in the same subjects while adjusting for important covariables such as height, pack-years, and respiratory symptoms and diseases. The results for smoking cessation showed a beneficial effect related to quitting that was largest for younger subjects and decreased linearly with age. For women, quitting resulted in an improvement in FEV1 of 4.3% at 20 yr of age which decreased to 2.5% by 80 yr of age. Men had an improvement of only 1.2% at 20 yr of age and no improvement at 80 yr of age. After excluding subjects with low initial function (FEV1/FVC in the lowest quartile) and those with only a single observation after quitting, men (n = 70) showed a significantly higher FEV1 improvement of 4% at 20 yr of age that decreased linearly to zero by age 80 yr. In contrast, women in this subgroup (n = 89) had nearly the same degree of improvement at all ages. The onset results showed mean FEV1 values after starting smoking that were higher at the younger ages (< 23 yr) and that decreased more rapidly with age, compared with nonsmoking mean estimates, in both sexes.
Consensus statement for inert gas washout measurement using multiple- and single- breath tests
Authors: Paul D. Robinson, Philipp Latzin, Sylvia Verbanck, Graham L. Hall, Alexander Horsley, Monika Gappa, Cindy Thamrin, Hubertus G.M. Arets, Paul Aurora, Susanne I. Fuchs, Gregory G. King, Sooky Lum, Kenneth Macleod, Manuel Paiva, Jane J. Pillow, Sarath Ranganathan, Felix Ratjen, Florian Singer, Samatha Sonnappa, Janet Stocks, Padmaja Subbarao, Bruce R. Thompson, Per M. Gustafsson
Journal: European Respiratory Journal (2013)

Inert gas washout tests, performed using the single- or multiple-breath washout technique, were first described over 60 years ago. As measures of ventilation distribution inhomogeneity, they offer complementary information to standard lung function tests, such as spirometry, as well as improved feasibility across wider age ranges and improved sensitivity in the detection of early lung damage. These benefits have led to a resurgence of interest in these techniques from manufacturers, clinicians and researchers, yet detailed guidelines for washout equipment specifications, test performance and analysis are lacking. This manuscript provides recommendations about these aspects, applicable to both the paediatric and adult testing environment, whilst outlining the important principles that are essential for the reader to understand. These recommendations are evidence based, where possible, but in many places represent expert opinion from a working group with a large collective experience in the techniques discussed. Finally, the important issues that remain unanswered are highlighted. By addressing these important issues and directing future research, the hope is to facilitate the incorporation of these promising tests into routine clinical practice.
Standard and Increased-Dose BEACOPP Chemotherapy Compared with COPP-ABVD for Advanced Hodgkin's Disease
Authors: Volker Diehl, Jeremy Franklin, Michael Pfreundschuh, Bernd Lathan, Ursula Paulus, Dirk Hasenclever, Hans Tesch, Richard Herrmann, Bernd Dörken, Hans-Konrad Müller-Hermelink, Eckhardt Dühmke, Markus Loeffler
Journal: New England Journal of Medicine (2003)

Faced with unsatisfactory results of treatment for advanced Hodgkin's disease, we investigated three combinations of chemotherapy.From 1993 to 1998, 1201 eligible patients 15 to 65 years of age who had newly diagnosed Hodgkin's disease in unfavorable stage IIB or IIIA or stage IIIB or IV were randomly assigned to receive eight cycles of cyclophosphamide, vincristine, procarbazine, and prednisone alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (COPP-ABVD); bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP); or increased-dose BEACOPP, each followed by local radiotherapy when indicated. Enrollment in the COPP-ABVD group was stopped in 1996 owing to inferior results.For the final analysis, 1195 of 1201 patients could be evaluated: 260 in the COPP-ABVD group, 469 in the BEACOPP group, and 466 in the increased-dose BEACOPP group; the median follow-up was 72, 54, and 51 months, respectively. The rate of freedom from treatment failure at five years was 69 percent in the COPP-ABVD group, 76 percent in the BEACOPP group, and 87 percent in the increased-dose BEACOPP group (P=0.04 for the comparison of the COPP-ABVD group with the BEACOPP group and P<0.001 for the comparison of the increased-dose BEACOPP group with the COPP-ABVD group and with the BEACOPP group), and the five-year rates of overall survival were 83 percent, 88 percent, and 91 percent, respectively (P=0.16 for the comparison of the COPP-ABVD group with the BEACOPP group, P=0.06 for the comparison of the BEACOPP group with the increased-dose BEACOPP group, and P=0.002 for the comparison of the COPP-ABVD group with the increased-dose BEACOPP group). Rates of early progression were significantly lower with increased-dose BEACOPP than with COPP-ABVD or standard BEACOPP.Increased-dose BEACOPP resulted in better tumor control and overall survival than did COPP-ABVD.
Insights Offered by Economic Analyses
Authors: William H. Herman
Journal: Diabetes Care (2014)

Economic analyses may be used to describe the costs of health care programs and to ensure that value is obtained for the money spent. This issue of Diabetes Care includes three economic analyses. The first describes the incremental costs of diabetes over a lifetime and highlights how interventions to prevent diabetes may reduce lifetime costs (1). The second demonstrates that although an expensive, intensive lifestyle intervention for type 2 diabetes does not reduce adverse cardiovascular outcomes over 10 years, it significantly reduces the costs of non-intervention−related medical care (2). The third demonstrates that although the use of the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria for the screening and diagnosis of gestational diabetes mellitus (GDM) results in a threefold increase in the number of people labeled as having GDM, it reduces the risk of maternal and neonatal adverse health outcomes and reduces costs (3). The first report highlights the enormous potential value of intervening in adults at high risk for type 2 diabetes to prevent its development. The second illustrates the importance of measuring economic outcomes in addition to standard clinical outcomes to fully assess the value of new treatments. The third demonstrates the importance of rigorously weighing the costs of screening and treatment against the costs of health outcomes when evaluating new approaches to care.

Zhuo et al. (1) linked data from the National Health Interview Survey (NHIS) and the Medical Expenditure Panel Survey with data describing survival to calculate and compare lifetime health care expenditures for people with and without diabetes. Because the NHIS includes information on age at diagnosis of diabetes, the authors were able to estimate diabetic patients’ medical spending and …
Complement factor H and the hemolytic uremic syndrome
Authors: John P. Atkinson, Timothy H.J. Goodship
Journal: The Journal of Experimental Medicine (2007)

Immune recognition is coupled to powerful proinflammatory effector pathways that must be tightly regulated. The ancient alternative pathway of complement activation is one such proinflammatory pathway. Genetic susceptibility factors have been identified in both regulators and activating components of the alternative pathway that are associated with thrombotic microangiopathies, glomerulonephritides, and chronic conditions featuring debris deposition. These observations indicate that excessive alternative pathway activation promotes thrombosis in the microvasculature and tissue damage during debris accumulation. Intriguingly, distinct genetic changes in factor H (FH), a key regulator of the alternative pathway, are associated with hemolytic uremic syndrome (HUS), membranoproliferative glomerulonephritis (dense deposit disease), or age-related macular degeneration (AMD). A mouse model of HUS designed to mirror human mutations in FH has now been developed, providing new understanding of the molecular pathogenesis of complement-related endothelial disorders.
Effect of Lower Targets for Blood Pressure and LDL Cholesterol on Atherosclerosis in Diabetes
Authors: Barbara V. Howard, Mary J. Roman, Richard B. Devereux, Jerome L. Fleg, James M. Galloway, Jeffrey A. Henderson, Wm. James Howard, Elisa T. Lee, Mihriye Mete, Bryce Poolaw, Robert E. Ratner, Marie Russell, Angela Silverman, Mario Stylianou, Jason G. Umans, Wenyu Wang, Matthew R. Weir, Neil J. Weissman, Charlton Wilson, Fawn Yeh, Jianhui Zhu
Journal: JAMA (2008)

<h3>Context</h3>Individuals with diabetes are at increased risk for cardiovascular disease (CVD), but more aggressive targets for risk factor control have not been tested.<h3>Objective</h3>To compare progression of subclinical atherosclerosis in adults with type 2 diabetes treated to reach aggressive targets of low-density lipoprotein cholesterol (LDL-C) of 70 mg/dL or lower and systolic blood pressure (SBP) of 115 mm Hg or lower vs standard targets of LDL-C of 100 mg/dL or lower and SBP of 130 mm Hg or lower.<h3>Design, Setting, and Participants</h3>A randomized, open-label, blinded-to-end point, 3-year trial from April 2003-July 2007 at 4 clinical centers in Oklahoma, Arizona, and South Dakota. Participants were 499 American Indian men and women aged 40 years or older with type 2 diabetes and no prior CVD events.<h3>Interventions</h3>Participants were randomized to aggressive (n=252) vs standard (n=247) treatment groups with stepped treatment algorithms defined for both.<h3>Main Outcome Measures</h3>Primary end point was progression of atherosclerosis measured by common carotid artery intimal medial thickness (IMT). Secondary end points were other carotid and cardiac ultrasonographic measures and clinical events.<h3>Results</h3>Mean target LDL-C and SBP levels for both groups were reached and maintained. Mean (95% confidence interval) levels for LDL-C in the last 12 months were 72 (69-75) and 104 (101-106) mg/dL and SBP levels were 117 (115-118) and 129 (128-130) mm Hg in the aggressive vs standard groups, respectively. Compared with baseline, IMT regressed in the aggressive group and progressed in the standard group (−0.012 mm vs 0.038 mm; P &lt; .001); carotid arterial cross-sectional area also regressed (−0.02 mm<sup>2</sup> vs 1.05 mm<sup>2</sup>; P &lt; .001); and there was greater decrease in left ventricular mass index (−2.4 g/m<sup>2.7</sup> vs −1.2 g/m<sup>2.7</sup>; P = .03) in the aggressive group. Rates of adverse events (38.5% and 26.7%; P = .005) and serious adverse events (n = 4 vs 1; P = .18) related to blood pressure medications were higher in the aggressive group. Clinical CVD events (1.6/100 and 1.5/100 person-years; P = .87) did not differ significantly between groups.<h3>Conclusions</h3>Reducing LDL-C and SBP to lower targets resulted in regression of carotid IMT and greater decrease in left ventricular mass in individuals with type 2 diabetes. Clinical events were lower than expected and did not differ significantly between groups. Further follow-up is needed to determine whether these improvements will result in lower long-term CVD event rates and costs and favorable risk-benefit outcomes.<h3>Trial Registration</h3>clinicaltrials.gov Identifier: NCT00047424
CD4+ T Cells Regulate Pulmonary Metastasis of Mammary Carcinomas by Enhancing Protumor Properties of Macrophages
Authors: David G. DeNardo, Jairo B. Barreto, Pauline Andreu, Lesley Vasquez, David Tawfik, Nikita Kolhatkar, Lisa M. Coussens
Journal: Cancer Cell (2009)
IgE to Furry Animal Allergen Components Was Associated with Asthma in a Population-Based Study of Adults
Authors: Sigrid Sjolander, Anders Bjerg, Linda Ekerljung, Otti Bengtsson-Gref, Magnus Borres, Eva Ronmark, Jan Lotvall, Bo Lundback
Journal: Journal of Allergy and Clinical Immunology (2015)

RATIONALE: Atopic sensitization increases the risk of asthma.Our aim was to investigate patterns of sensitization to allergens and allergen components in relation to asthma among adults in a Swedish populationbased sample.METHODS: A questionnaire targeting asthma was sent to 30 000 randomly selected adults (16-75 y) in west Sweden.Of the 18 087 responders, a randomly selected sample of 2000 subjects and in addition all 1536 subjects reporting asthma were invited to clinical examinations.Sera were received from 906 subjects with asthma and from 1000 without reported asthma (controls) and were tested for three IgE panels of inhalant and food allergens.Samples with a level of IgE >0.35 kU A /l were further analyzed for IgE against each individual allergen and nine allergen components related to furry animals.RESULTS: The risk of being sensitized to any of the 21 tested allergens was significantly higher in the asthma group.The risk was highest for individuals sensitized to furry animals (risk ratios 4,5-7,9).The level of IgE to animal allergens was also significantly higher in the asthma group.Cosensitization to more than one cat and/or dog allergen component conferred a greater risk for asthma.Simultaneous sensitization to the cat allergens Fel d 1 and Fel d 4 was associated with asthma.CONCLUSIONS: In this large population-based study subjects with asthma were commonly co-sensitized to more than one animal allergen component, especially to Fel d 1 and Fel d 4. Component-resolved analysis has the potential to increase precision when assessing asthma in adults.
Therapeutic and diagnostic implications of Hsp90 activation
Authors: Adeela Kamal, Marcus F Boehm, Francis J Burrows
Journal: Trends in Molecular Medicine (2004)

The molecular chaperone heat-shock protein 90 (Hsp90) is involved in the stabilization and conformational maturation of many signaling proteins that are deregulated in cancers. Hsp90 inhibition results in the proteasomal degradation of these client proteins and leads to potent antitumor activity. The Hsp90 inhibitor 17-allylaminogeldanamycin (17-AAG) is presently in clinical trials. Recent work has identified the role of Hsp90 in multiple signal transduction pathways and revealed that the molecular mechanism of tumor selectivity by Hsp90 inhibitors is the result of an activated, high-affinity conformation of Hsp90 in tumors. This review discusses these recent advances in the understanding of tumor Hsp90 for the treatment and diagnosis of cancer. In addition, the role of Hsp90 in non-oncological diseases will also be discussed.
EULAR recommendations for terminology and research in individuals at risk of rheumatoid arthritis: report from the Study Group for Risk Factors for Rheumatoid Arthritis
Authors: Danielle M Gerlag, Karim Raza, Lisa G M van Baarsen, Elisabeth Brouwer, Christopher D Buckley, Gerd R Burmester, Cem Gabay, Anca I Catrina, Andrew P Cope, François Cornelis, Solbritt Rantapää Dahlqvist, Paul Emery, Stephen Eyre, Axel Finckh, Steffen Gay, Johanna M Hazes, Annette van der Helm-van Mil, Tom W J Huizinga, Lars Klareskog, Tore K Kvien, Cathryn Lewis, Klaus P Machold, Johan Rönnelid, Dirkjan van Schaardenburg, Georg Schett, Josef S Smolen, Sue Thomas, Jane Worthington, Paul P Tak
Journal: Annals of the Rheumatic Diseases (2012)

The Study Group for Risk Factors for Rheumatoid Arthritis was established by the EULAR Standing Committee on Investigative Rheumatology to facilitate research into the preclinical and earliest clinically apparent phases of rheumatoid arthritis (RA). This report describes the recommendation for terminology to be used to define specific subgroups during different phases of disease, and defines the priorities for research in this area. Terminology was discussed by way of a three-stage structured process: A provisional list of descriptors for each of the possible phases preceding the diagnosis of RA were circulated to members of the study group for review and feedback. Anonymised comments from the members on this list were fed back to participants before a 2-day meeting. 18 participants met to discuss these data, agree terminologies and prioritise important research questions. The study group recommended that, in prospective studies, individuals without RA are described as having: genetic risk factors for RA; environmental risk factors for RA; systemic autoimmunity associated with RA; symptoms without clinical arthritis; unclassified arthritis; which may be used in a combinatorial manner. It was recommended that the prefix ‘pre-RA with:’ could be used before any/any combination of the five points above but only to describe retrospectively a phase that an individual had progressed through once it was known that they have developed RA. An approach to dating disease onset was recommended. In addition, important areas for research were proposed, including research of other tissues in which an adaptive immune response may be initiated, and the identification of additional risk factors and biomarkers for the development of RA, its progression and the development of extra-articular features. These recommendations provide guidance on approaches to describe phases before the development of RA that will facilitate communication between researchers and comparisons between studies. A number of research questions have been defined, requiring new cohorts to be established and new techniques to be developed to image and collect material from different sites.
Trans-ethnic genome-wide association studies: advantages and challenges of mapping in diverse populations
Authors: Yun R Li, Brendan J Keating
Journal: Genome Medicine (2014)

Abstract Genome-wide association studies (GWASs) are the method most often used by geneticists to interrogate the human genome, and they provide a cost-effective way to identify the genetic variants underpinning complex traits and diseases. Most initial GWASs have focused on genetically homogeneous cohorts from European populations given the limited availability of ethnic minority samples and so as to limit population stratification effects. Transethnic studies have been invaluable in explaining the heritability of common quantitative traits, such as height, and in examining the genetic architecture of complex diseases, such as type 2 diabetes. They provide an opportunity for large-scale signal replication in independent populations and for cross-population meta-analyses to boost statistical power. In addition, transethnic GWASs enable prioritization of candidate genes, fine-mapping of functional variants, and potentially identification of SNPs associated with disease risk in admixed populations, by taking advantage of natural differences in genomic linkage disequilibrium across ethnically diverse populations. Recent efforts to assess the biological function of variants identified by GWAS have highlighted the need for large-scale replication, meta-analyses and fine-mapping across worldwide populations of ethnically diverse genetic ancestries. Here, we review recent advances and new approaches that are important to consider when performing, designing or interpreting transethnic GWASs, and we highlight existing challenges, such as the limited ability to handle heterogeneity in linkage disequilibrium across populations and limitations in dissecting complex architectures, such as those found in recently admixed populations.
Receptor expression in synovial fluid neutrophils from patients with rheumatoid arthritis.
Authors: F Watson, J.J Robinson, M Phelan, R.C Bucknall, S.W Edwards
Journal: Annals of the Rheumatic Diseases (1993)

The aim of this study was to determine if neutrophils isolated from the blood and synovial fluid of patients with rheumatoid arthritis had patterns of receptor expression resembling those of blood neutrophils from controls which had been activated and primed in vitro. Fluorescence activated cell sorting was used to measure receptor expression in paired blood and synovial fluid neutrophils from patients and in control neutrophils exposed to phorbol myristate acetate and granulocyte-macrophage colony stimulating factor. There was no significant difference in the patterns of receptor expression in blood neutrophils from patients and healthy controls, but neutrophils in the synovial fluid had been primed and activated within the joint. About 50% of rheumatoid synovial fluid neutrophil samples expressed Fc gamma RI, a high affinity receptor for monomeric IgG, which is only expressed in neutrophils exposed to cytokines. Synovial fluid neutrophils are activated and primed within the inflamed joint and hence their ability to respond to activating factors such as immune complexes will be modulated. As the expression of Fc gamma RI requires active biosynthesis, this work indicates that selective gene activation occurs when neutrophils are recruited into rheumatoid joints.
Juvenile Exposure to Anthracyclines Impairs Cardiac Progenitor Cell Function and Vascularization Resulting in Greater Susceptibility to Stress-Induced Myocardial Injury in Adult Mice
Authors: Chengqun Huang, Xiaoxue Zhang, Jennifer M. Ramil, Shivaji Rikka, Lucy Kim, Youngil Lee, Natalie A. Gude, Patricia A. Thistlethwaite, Mark A. Sussman, Roberta A. Gottlieb, Åsa B. Gustafsson
Journal: Circulation (2010)

Background— The anthracycline doxorubicin is an effective chemotherapeutic agent used to treat pediatric cancers but is associated with cardiotoxicity that can manifest many years after the initial exposure. To date, very little is known about the mechanism of this late-onset cardiotoxicity. Methods and Results— To understand this problem, we developed a pediatric model of late-onset doxorubicin-induced cardiotoxicity in which juvenile mice were exposed to doxorubicin, using a cumulative dose that did not induce acute cardiotoxicity. These mice developed normally and had no obvious cardiac abnormalities as adults. However, evaluation of the vasculature revealed that juvenile doxorubicin exposure impaired vascular development, resulting in abnormal vascular architecture in the hearts with less branching and decreased capillary density. Both physiological and pathological stress induced late-onset cardiotoxicity in the adult doxorubicin-treated mice. Moreover, adult mice subjected to myocardial infarction developed rapid heart failure, which correlated with a failure to increase capillary density in the injured area. Progenitor cells participate in regeneration and blood vessel formation after a myocardial infarction, but doxorubicin-treated mice had fewer progenitor cells in the infarct border zone. Interestingly, doxorubicin treatment reduced proliferation and differentiation of the progenitor cells into cells of cardiac lineages. Conclusions— Our data suggest that anthracycline treatment impairs vascular development as well as progenitor cell function in the young heart, resulting in an adult heart that is more susceptible to stress.