tbuckley/cabot-search huggingface dataset:
A Randomized Controlled Trial in Second-Generation Zotarolimus-Eluting Resolute Stents Versus Everolimus-Eluting Xience V Stents in Real-World Patients
Authors: Clemens von Birgelen, Mounir W.Z. Basalus, Kenneth Tandjung, K. Gert van Houwelingen, Martin G. Stoel, J.(Hans) W. Louwerenburg, Gerard C.M. Linssen, Salah A.M. Saïd, Miep A.W.J. Kleijne, Hanim Sen, Marije M. Löwik, Job van der Palen, Patrick M.J. Verhorst, Frits H.A.F. de Man
Journal: Journal of the American College of Cardiology (2012)

The aim of this study was to compare the safety and efficacy of Resolute zotarolimus-eluting stents (ZES) (Medtronic Cardiovascular, Santa Rosa, California) with Xience V everolimus-eluting stents (EES) (Abbott Vascular Devices, Santa Clara, California) at 1-year follow-up.Only 1 randomized trial previously compared these stents.This investigator-initiated, patient-blinded, randomized noninferiority study had limited exclusion criteria (acute ST-segment elevation myocardial infarctions not eligible). Patients (n = 1,391; 81.4% of eligible population) were randomly assigned to ZES (n = 697) or EES (n = 694). Liberal use of stent post-dilation was encouraged. Cardiac biomarkers were systematically assessed. The primary endpoint was target vessel failure (TVF), a composite of cardiac death, myocardial infarction not clearly attributable to non-target vessels, and clinically indicated target-vessel revascularization. An external independent research organization performed clinical event adjudication (100% follow-up data available). Analysis was by intention-to-treat.Acute coronary syndromes were present in 52% and "off-label" feature in 77% of patients. Of the lesions, 70% were type B2/C; the post-dilation rate was very high (82%). In ZES and EES, TVF occurred in 8.2% and 8.1%, respectively (absolute risk-difference 0.1%; 95% confidence interval: -2.8% to 3.0%, p(noninferiority) = 0.001). There was no significant between-group difference in TVF components. The definite-or-probable stent thrombosis rates were relatively low and similar for ZES and EES (0.9% and 1.2%, respectively, p = 0.59). Definite stent thrombosis rates were also low (0.58% and 0%, respectively, p = 0.12). In EES, probable stent thrombosis beyond day 8 was observed only in patients not adhering to dual antiplatelet therapy.Resolute ZES were noninferior to Xience V EES in treating "real-world" patients with a vast majority of complex lesions and "off-label" indications for drug-eluting stents, which were implanted with liberal use of post-dilation. (The Real-World Endeavor Resolute Versus XIENCE V Drug-Eluting SteNt Study: Head-to-head Comparison of Clinical Outcome After Implantation of Second Generation Drug-eluting Stents in a Real World Scenario; NCT01066650).
Time to progression of pancreatic ductal adenocarcinoma from low-to-high tumour stages
Authors: Jun Yu, Amanda L Blackford, Marco dal Molin, Christopher L Wolfgang, Michael Goggins
Journal: Gut (2015)

<h3>Objective</h3> Although pancreatic ductal adenocarcinoma is considered a rapidly progressive disease, mathematical models estimate that it takes many years for an initiating pancreatic cancer cell to grow into an advanced stage cancer. In order to estimate the time it takes for a pancreatic cancer to progress through different tumor, node, metastasis (TNM) stages, we compared the mean age of patients with pancreatic cancers of different sizes and stages. <h3>Design</h3> Patient age, tumour size, stage and demographic information were analysed for 13 131 patients with pancreatic ductal adenocarcinoma entered into the National Cancer Institute9s Surveillance, Epidemiology and End Results (SEER) database. Multiple linear regression models for age were generated, adjusting for patient ethnicity, gender, tumour location and neoplastic grades. <h3>Results</h3> African-American ethnicity and male gender were associated with an earlier age at diagnosis. Patients with stage I cancers (mean age 64.8 years) were on average 1.3 adjusted years younger at diagnosis than those with stage IV cancers (p=0.001). Among patients without distant metastases, those with T1 stage cancers were on average 1.06 and 1.19 adjusted years younger, respectively, than patients with T3 or T4 cancers (p=0.03 for both). Among patients with stage IIB cancers, those with T1/T2 cancers were 0.79 adjusted years younger than those with T3 cancers (p=0.06). There was no significant difference in the mean adjusted age of patients with stage IA versus stage IB cancers. <h3>Conclusions</h3> These results are consistent with the hypothesis that once pancreatic ductal adenocarcinomas become detectable clinically progression from low-stage to advanced-stage disease is rapid.
Ensuring the Fiscal Sustainability of Health Care Reform
Authors: Michael E Chernew, Lindsay Sabik, Amitabh Chandra, Joseph P Newhouse
Journal: New England Journal of Medicine (2009)

Much of the recent health care reform debate has focused on achieving budget neutrality over a 10-year period, but this goal is less important than the reform's long-run fiscal sustainability. If the rate of growth of health care spending continues to exceed the rate of income growth by its historical margin of more than 2 percentage points, the consequences for beneficiaries, federal and state budgets, and the entire economy — given the implied increase in tax rates and forgone consumption — will be dire.1 For this reason, health care reform is an economic issue as much as, if not more . . .
Mitochondrial calcium transporting pathways during hypoxia and reoxygenation in single rat cardiomyocytes
Authors: Elinor J. Griffiths, Christopher J. Ocampo, Jason S. Savage, Guy A. Rutter, Richard G. Hansford, Michael D. Stern, Howard S. Silverman
Journal: Cardiovascular Research (1998)

Objective: Mitochondrial [Ca2+] ([Ca2+]m) rises in parallel with cytosolic [Ca2+] ([Ca2+]c) following ATP-depletion rigor contracture induced by hypoxia in isolated cardiomyocytes. We investigated the pathways involved in the hypoxia induced changes in [Ca2+]m by using known inhibitors of mitochondrial Ca2+ transport, namely ruthenium red, an inhibitor of the Ca2+ uniporter (the normal influx route) and clonazepam, an inhibitor of Na+/Ca2+ exchange, (the normal efflux route). Methods: [Ca2+]m was determined from indo-1/am loaded rat myocytes where the cytosolic fluorescence signal had been quenched by superfusion with Mn2+. [Ca2+]c was measured by loading myocytes with indo-1 pentapotassium salt during the isolation procedure. Cells were placed in a specially developed chamber for induction of hypoxia and reoxygenated 40 min after rigor development. Results: 50% of control cells hypercontracted upon reoxygenation; this correlated with a [Ca2+]m or [Ca2+]c higher than approximately 350 nM at the end of rigor. Clonazepam completely abolished the rigor-induced rise in [Ca2+]m but not [Ca2+]c. On reoxygenation [Ca2+]m increased over the first 5 min and remained elevated whereas [Ca2+]c fell. In the presence of ruthenium red a dramatic increase in [Ca2+]m occurred 5–10 min after rigor development (the indo-1 fluorescence signal was saturated); [Ca2+]c also increased but to a lesser extent. On reoxygenation, [Ca2+]m fell rapidly even though cells hypercontracted and [Ca2+]c remained elevated. Conclusions: During hypoxia following rigor development Ca2+ uptake into mitochondria occurs largely via the Na+/Ca2+ exchanger rather than the Ca2+ uniporter whereas on reoxygenation the transporters resume their normal directionality.
Tumor necrosis factor-alpha and myocardial remodeling in progression of heart failure: a current perspective
Authors: William S Bradham, Biykem Bozkurt, Himali Gunasinghe, Douglas Mann, Francis G Spinale
Journal: Cardiovascular Research (2002)

A milestone in the progression of congestive heart failure (CHF) is myocardial remodeling. Left ventricular (LV) remodeling during the progression of CHF is accompanied by changes in the structure of the myocardial extracellular matrix. Recent clinical and experimental studies have noted that increased release of tumor necrosis factor alpha (TNF-α) can contribute to LV myocardial remodeling. Experimental studies have noted that the induction of TNF-α can result in LV dilation and proceed to LV pump dysfunction. The biological effects of TNF-α are mediated through TNF receptors that are present on all nucleated cells in the heart. TNF receptor activation can induce a number of cellular and molecular events which contribute to LV remodeling in CHF, and include changes in myocyte size and viability and alterations in myocardial structure/composition. In vitro studies have demonstrated that TNF receptor activation can cause the induction of a proteolytic system. This proteolytic system, the matrix metalloproteinases (MMPs), is upregulated in models of LV dysfunction and possesses the capacity to degrade a wide variety of extracellular matrix components. Therefore, one pathway by which TNF-α can influence LV myocardial remodeling is through the induction of a specific portfolio of MMP species. Future basic and clinical studies which directly alter TNF receptor activity and measure myocardial MMP species and the relation to LV remodeling will provide new insight into this disease process and future therapeutic modalities.
Induction of B7-1 in podocytes is associated with nephrotic syndrome
Authors: Jochen Reiser, Gero von Gersdorff, Martin Loos, Jun Oh, Katsuhiko Asanuma, Laura Giardino, Maria Pia Rastaldi, Novella Calvaresi, Haruko Watanabe, Karin Schwarz, Christian Faul, Matthias Kretzler, Anne Davidson, Hikaru Sugimoto, Raghu Kalluri, Arlene H. Sharpe, Jordan A. Kreidberg, Peter Mundel
Journal: Journal of Clinical Investigation (2004)

Kidney podocytes and their slit diaphragms form the final barrier to urinary protein loss. This explains why podocyte injury is typically associated with nephrotic syndrome. The present study uncovered an unanticipated novel role for costimulatory molecule B7-1 in podocytes as an inducible modifier of glomerular permselectivity. B7-1 in podocytes was found in genetic, drug-induced, immune-mediated, and bacterial toxin–induced experimental kidney diseases with nephrotic syndrome. The clinical significance of our results is underscored by the observation that podocyte expression of B7-1 correlated with the severity of human lupus nephritis. In vivo, exposure to low-dose LPS rapidly upregulates B7-1 in podocytes of WT and SCID mice, leading to nephrotic-range proteinuria. Mice lacking B7-1 are protected from LPS-induced nephrotic syndrome, suggesting a link between podocyte B7-1 expression and proteinuria. LPS signaling through toll-like receptor-4 reorganized the podocyte actin cytoskeleton in vitro, and activation of B7-1 in cultured podocytes led to reorganization of vital slit diaphragm proteins. In summary, upregulation of B7-1 in podocytes may contribute to the pathogenesis of proteinuria by disrupting the glomerular filter and provides a novel molecular target to tackle proteinuric kidney diseases. Our findings suggest a novel function for B7-1 in danger signaling by nonimmune cells.
Study of the Media’s Potential Influence on Prospective Research Participants’ Understanding of and Motivations for Participation in a High-Profile Phase I Trial
Authors: Rebecca D. Pentz, Anne L. Flamm, Jeremy Sugarman, Marlene Z. Cohen, G. Daniel Ayers, Roy S. Herbst, James L. Abbruzzese
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To describe prospective participants’ initial source of information about, understanding of, and motivation to participate in a phase I clinical trial of the antiangiogenesis agent human recombinant endostatin. PATIENTS AND METHODS: We surveyed 100 of 130 persons referred to the endostatin trial between October 1999 and November 2000 and analyzed media coverage of the agent from 1997 to 2000. RESULTS: Forty-seven percent of survey respondents first heard about the trial from media reports. Fifty-one percent of these subsequently contacted their physicians. Thirty-three percent of respondents correctly understood the purpose of the trial. Seventy-nine respondents were interviewed before they met trial investigators to discuss the trial. Of these, those who first heard about endostatin from the media were five times more likely to understand correctly the trial’s purpose than those who first heard from other sources. Seventy-four percent (70 of 95) of respondents cited hope for personal benefit as the main reason for their willingness to enroll. Those who first heard about endostatin from the media were no more motivated by hope of personal benefit (77%) than those who first heard from other sources (71%) (P = .46). Ninety-nine percent of all respondents cited “joining the study gives me hope” as a contributing factor in their decision making about the trial. CONCLUSION: Media coverage prompted prospective participants to contact their physicians but did not seem to hinder understanding nor could it be shown to heighten their hope for personal benefit.
Addressing liver disease in the UK: a blueprint for attaining excellence in health care and reducing premature mortality from lifestyle issues of excess consumption of alcohol, obesity, and viral hepatitis
Authors: Roger Williams, Richard Aspinall, Mark Bellis, Ginette Camps-Walsh, Matthew Cramp, Anil Dhawan, James Ferguson, Dan Forton, Graham Foster, Sir Ian Gilmore, Matthew Hickman, Mark Hudson, Deirdre Kelly, Andrew Langford, Martin Lombard, Louise Longworth, Natasha Martin, Kieran Moriarty, Philip Newsome, John O'Grady, Rachel Pryke, Harry Rutter, Stephen Ryder, Nick Sheron, Tom Smith
Journal: The Lancet (2014)
Thymic function in juvenile idiopathic arthritis
Authors: A R Lorenzi, T A Morgan, A Anderson, J Catterall, A M Patterson, H E Foster, J D Isaacs
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> Thymic function declines exponentially with age. Impaired thymic function has been associated with autoimmune disease in adults but has never been formally assessed in childhood autoimmunity. Therefore, thymic function in children with the autoimmune disease juvenile idiopathic arthritis (JIA) was determined. <h3>Methods:</h3> Thymic function was measured in 70 children and young adults with JIA (age range 2.1–30.8 (median 10.4)) and 110 healthy age-matched controls using four independent assays. T cell receptor excision circles (WBLogTREC/ml) and the proportion of CD4<sup>+</sup> CD45RA<sup>+</sup>CD31<sup>+</sup> T cells (representing recent thymic emigrants; %RTEs) were quantified and intrathymic proliferation measured by calculating the αTREC/ΣβTREC ratio. Lastly, regulatory T cells (T<sub>Reg</sub>) of thymic origin (CD4<sup>+</sup>FOXP3<sup>+</sup>) were quantified in peripheral blood to assess the ability of the thymus in JIA to generate this T cell subset. <h3>Results:</h3> Thymic function was equivalent by all four parameters in JIA when compared with the control population. Furthermore, there was no consistent effect of JIA subtype on thymic function, although intrathymic proliferation was higher in the small rheumatoid factor (RF)<sup>+</sup> polyarticular group. There were no significant effects of disease-modifying antirheumatic drugs (DMARDs) or oral corticosteroids on thymic function, although those with the worst prognostic ILAR (International League of Associations for Rheumatology) subtypes were also those most likely to be on a DMARD. <h3>Conclusions:</h3> It is demonstrated that children and young adults with JIA, unlike adults with autoimmune diseases, have thymic function that is comparable with that of healthy controls. The varied pathologies represented by the term "JIA" suggest this observation may not be disease specific and raises interesting questions about the aetiology of thymic impairment in adult autoimmunity.
National Kidney Foundation Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification
Authors: Andrew S. Levey, Josef Coresh, Ethan Balk, Annamaria T. Kausz, Adeera Levin, Michael W. Steffes, Ronald J. Hogg, Ronald D. Perrone, Joseph Lau, Garabed Eknoyan
Journal: Annals of Internal Medicine (2003)

Chronic kidney disease is a worldwide public health problem with an increasing incidence and prevalence, poor outcomes, and high cost. Outcomes of chronic kidney disease include not only kidney failure but also complications of decreased kidney function and cardiovascular disease. Current evidence suggests that some of these adverse outcomes can be prevented or delayed by early detection and treatment. Unfortunately, chronic kidney disease is underdiagnosed and undertreated, in part as a result of lack of agreement on a definition and classification of its stages of progression. Recent clinical practice guidelines by the National Kidney Foundation 1) define chronic kidney disease and classify its stages, regardless of underlying cause, 2) evaluate laboratory measurements for the clinical assessment of kidney disease, 3) associate the level of kidney function with complications of chronic kidney disease, and 4) stratify the risk for loss of kidney function and development of cardiovascular disease. The guidelines were developed by using an approach based on the procedure outlined by the Agency for Healthcare Research and Quality. This paper presents the definition and five-stage classification system of chronic kidney disease and summarizes the major recommendations on early detection in adults. Recommendations include identifying persons at increased risk (those with diabetes, those with hypertension, those with a family history of chronic kidney disease, those older than 60 years of age, or those with U.S. racial or ethnic minority status), detecting kidney damage by measuring the albumin-creatinine ratio in untimed ("spot") urine specimens, and estimating the glomerular filtration rate from serum creatinine measurements by using prediction equations. Because of the high prevalence of early stages of chronic kidney disease in the general population (approximately 11% of adults), this information is particularly important for general internists and specialists.
Breast Cancer Risk and the DNA Double-Strand Break End-Joining Capacity of Nonhomologous End-Joining Genes Are Affected by <b> <i>BRCA1</i> </b>
Authors: Da-Tian Bau, Yi-Ping Fu, Shou-Tung Chen, Ting-Chih Cheng, Jyh-Cherng Yu, Pei-Ei Wu, Chen-Yang Shen
Journal: Cancer Research (2004)

Abstract A tumorigenic role of the nonhomologous end-joining (NHEJ) pathway for the repair of DNA double-strand breaks (DSBs) has been suggested by the finding of a significant association between increased breast cancer risk and a cooperative effect of single nucleotide polymorphisms (SNPs) in NHEJ genes. However, the lack of an association between hereditary breast cancer and defective NHEJ genes prevents conclusions from being drawn about a link between NHEJ and breast cancer development. Recently, BRCA1-deficient mouse embryonic fibroblasts were found to have significantly reduced NHEJ activity, suggesting an accessory role of BRCA1 in NHEJ. The present study was performed to confirm this observation in human breast cancer cell lines and to examine whether the interaction between BRCA1 and NHEJ was of tumorigenic significance. Support for this hypothesis came from the findings that (a) a case-control study (469 breast cancer patients and 740 healthy controls) showed that the breast cancer risk associated with high-risk genotypes of NHEJ genes was significantly modified by the BRCA1 genotype. A significant increase in the cancer risk associated either with harboring one additional putative high-risk NHEJ genotype or with the joint effect of having reproductive risk factors (reflected by an interval of ≥12 years between menarche and first full-term pregnancy) and a higher number of high-risk genotypes of the NHEJ genes was only seen in women with at least one variant BRCA1 allele (i.e., the Glu/Gly or Gly/Gly forms of BRCA1 Glu1038Gly); and (b) a phenotype-based study measuring in vitro and in vivo NHEJ capacity showed that the precise end-joining capacity was different in breast cancer cell lines with different BRCA1 statuses being higher in BRCA1-expressing MCF-7 cells than in HCC1937 cells (defective BRCA1 expression). Furthermore, this end-joining capacity was decreased in MCF-7 cells in which BRCA1 expression was blocked using small interfering RNA and increased in HCC1937 transfected with full-length BRCA1. Because BRCA1 is a well-documented breast cancer susceptibility gene, this association between NHEJ and BRCA1 not only suggests a role of BRCA1 in NHEJ but also provides essential support for the tumorigenic contribution of NHEJ in breast cancer development.
The genomic origins of asthma
Authors: Sunita Sharma, Divya Chhabra, Alvin T Kho, Lystra P Hayden, Kelan G Tantisira, Scott T Weiss
Journal: Thorax (2014)

Lung function tracks from the earliest age that it can be reliably measured. Genome wide association studies suggest that most variants identified for common complex traits are regulatory in function and active during fetal development. Fetal programming of gene expression during development is critical to the formation of a normal lung. An understanding of how fetal developmental genes related to diseases of the lungs and airways is a critical area for research. This review article considers the developmental origins hypothesis, the stages of normal lung development and a variety of environmental exposures that might influence the developmental process: in utero cigarette smoke exposure, vitamin D and folate. We conclude with some information on developmental genes and asthma.
Effects of long-term verapamil treatment on blood pressure, cardiac hypertrophy and collagen metabolism in spontaneously hypertensive rats
Authors: H. J RUSKOAHO, E.-R. SAVOLAINEN
Journal: Cardiovascular Research (1985)

The effects of long-term treatment with verapamil on blood pressure, cardiac hypertrophy and collagen content, collagen concentration and prolyl hydroxylase activity were studied in spontaneously hypertensive rats (SHR). Verapamil administration (0.75 mg . ml-1 in drinking water) was commenced: to pregnant SHR 3 to 5 days before delivery and continued to the mothers and offspring during the nursing period; or to SHR at 10 weeks of age. Both groups were maintained on verapamil treatment up to the age of 45 weeks. Verapamil treatment significantly decreased blood pressure, heart rate and the ratio of ventricular weight to body weight in treated SHR. Verapamil did not significantly change the cardiac collagen concentration and prolyl hydroxylase activity. Since, however, the cardiac muscle mass was diminished by verapamil administration, treatment actually slightly reduced the collagen content of the heart. In the aorta collagen concentration was increased by verapamil treatment. Contrary to these results, minoxidil treatment was observed to increase the cardiac collagen concentration, content and prolyl hydroxylase activity in SHR. These results suggest that the factors governing myocardial connective tissue proliferation and regression may be independent of those governing muscle fibre hypertrophy and that particular drug actions on myocardial collagen metabolism must be taken into account.