tbuckley/cabot-search huggingface dataset:
NIH Consensus conference. Triglyceride, high-density lipoprotein, and coronary heart disease. NIH Consensus Development Panel on Triglyceride, High-Density Lipoprotein, and Coronary Heart Disease
Authors: E. Rapaport, D. W. Bilheimer, A. V. Chobanian, D. P. Hajjar, C. M. Hawkins, G. M. Hutchins, P. M. Kris-Etherton, Russell V Luepker, H. D. McIntosh, C. J. Pepine, W. A. Pettinger, G. Schonfeld, D. F. Tulcin, M. H. Criqui, D. J. Gordon, M. A. Austin, G. Assmann, G. Heiss, T. L. Bush
Journal: JAMA (1993)

GREAT progress has been made over the past 30 years in identifying cardiovascular risk factors and in developing and implementing measures to correct them. The Adult Treatment Panel of the National Cholesterol Education Program developed guidelines in 1988 that identified low-density lipoprotein (LDL) as the major atherogenic lipoprotein and high levels of LDL cholesterol (LDL-C) as the primary target for cholesterol-lowering therapy. Since these guidelines were developed, the scientific database has significantly expanded. Genetic investigations into familial dyslipidemias, advances in molecular biology, animal experiments, human observational studies, lipid metabolic studies, epidemiologic data, and the results of interventional clinical trials looking at mortality, cardiovascular end points, and angiographic changes in atheromatous lesions have created interest in further examination of the role of high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs) in the pathogenesis of coronary artery disease. To address these questions, the National Heart, Lung, and Blood Institute and the Office of
Blockade of TGF-beta by catheter-based gene transfer of a soluble TGF-beta type II receptor inhibits neointima in a porcine coronary artery after stenting
Authors: Ick-Mo Chung, Hikaru Ueno, Donghoon Choi, Yangsoo Jang, Gil-Ja Shin, Youngmi K. Pak, Junwoo Kim, Chan Park
Journal: Journal of the American College of Cardiology (2003)
Collagenase Secretion by Human Breast Neoplasms: A Clinicopathologic Investigation&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: D J Ogilvie, J A Hailey, S F Juacaba, E C Lee, D Tarin
Journal: JNCI Journal of the National Cancer Institute (1985)

Evidence is presented that biopsy specimens from fibroadenomas, benign cystic lesions, and carcinomas of the human breast can produce in organ culture a neutral protease capable of digesting type I collagen. This enzyme activity, measured with the use of a radioactive release assay, was characterized as true vertebrate collagenase and occurred in both active and latent (requiring trypsin activation) forms. For the two types of benign breast lesion studied, collagenase secretion was significantly higher from fibroadenomas than from benign cystic tissue. Breast carcinomas, however, exhibited a wide quantitative spectrum of collagenase secretion, encompassing the extremes observed for the benign lesions and showing no correlation with histologic type. These results, while providing a plausible mechanism for the marked collagen degradation seen in disseminating neoplasms, demonstrate that high collagenase secretory activity is not pathognomonic of invasive behavior. The findings, however, indicate disordered regulation of collagenase activity in malignant tumors.
Risk factors, atherosclerosis, and cardiovascular disease among Aboriginal people in Canada: the Study of Health Assessment and Risk Evaluation in Aboriginal Peoples (SHARE-AP)
Authors: Sonia S Anand, Salim Yusuf, Ruby Jacobs, A Darlene Davis, Qilong Yi, Hertzel Gerstein, Patricia A Montague, Eva Lonn
Journal: The Lancet (2001)
The therapeutic activity of low-dose irradiation on experimental arthritis depends on the induction of endogenous regulatory T cell activity
Authors: Ling Weng, Richard O. Williams, Pedro L Vieira, Gavin Screaton, Marc Feldmann, Francesco Dazzi
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Background</h3> It has been widely demonstrated that a quantitative and/or qualitative impairment of regulatory T cells (T<sub>regs</sub>) play a fundamental role in the initiation and persistence of rheumatoid arthritis (RA) in animal models and in patients. In the present work it is demonstrated that partial myeloablation induces a relative expansion of T<sub>regs</sub> that is sufficient to mediate immunological tolerance. <h3>Objectives</h3> (1) To test the ability of low-intensity myeloablation mediated T<sub>reg</sub> activation to prevent and/or to treat experimental arthritis using the collagen-induced arthritis (CIA) model and (2) to clarify the role of T<sub>reg</sub> in mediating the beneficial effect. <h3>Methods</h3> Low-dose irradiation was used before the induction of arthritis or at the onset of disease. The role of T<sub>regs</sub> (CD4CD25forkhead box P3 (FoxP3)<sup>+</sup> cells) and their suppressive activity was assessed by testing their functional activities ex vivo after the treatment and by their in vivo depletion before the treatment. <h3>Results</h3> It was observed that irradiation ameliorated CIA before or after disease induction. T<sub>regs</sub> appear to play a fundamental role in the therapeutic efficacy of irradiation, because the depletion of CD25 or folate receptor (FR)4<sup>+</sup> cells with specific antibodies before the treatment abolished the beneficial effects. The therapeutic efficacy was associated with an increment in the proportion of T<sub>regs</sub> despite the overall reduction in lymphocyte counts. Furthermore, a decline in the percentage of CD4CD25FoxP3<sup>+</sup> T<sub>regs</sub> was associated with disease flare. <h3>Conclusion</h3> In vivo T<sub>reg</sub> expansion is a feasible and effective approach in the treatment of autoimmune diseases.
A–Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance—Part 37
Authors: J Pearce, L E Norton, D S Senchina, L L Spriet, L M Burke, S J Stear, L M Castell
Journal: British Journal of Sports Medicine (2012)

Finishing up letter ‘S’, and in another rare departure from our A–Z list of supplement components, we decided it was important to address the issue of ‘stacking’—strategically combining or cycling the use of different supplement products. While this originated and still resonates mostly with body builders, it is an issue that has consequences for athletes of all types and levels due to the prevalence of multiple supplement use. Moving on to ‘T’ we deal with taurine, theobromine and theophylline: all three of these can be found in sports drinks/bars, which purport to stimulate performance.

### J Pearce, L E Norton

In this summary, stacking is defined as the consumption of two or more supplements at the same time in an attempt to maximise results. This practice originated from anabolic steroid regimes of body builders and other resistance training athletes where products were combined, often to address the side effects or potentiate the actions of individual products.1 A more global view of supplement stacking in sports nutrition finds that supplement combinations can be deliberate or unintentional. Deliberate stacking aims to take advantage of positive physiological responses that arise from combining nutrients, foods or compounds (eg, vitamin C enhancing iron absorption). Few studies have examined the possible benefits to stacking2–5 and have produced equivocal results despite theoretical support. Combining creatine with β-alanine had a unique effect on delaying fatigue while stacking creatine with hydroxy-B-methylbutyrate produced additive effects on lean body mass.4 ,5 The combination of β-alanine (intracellular) and bicarbonate (extracellular) buffers for events involving sustained high-intensity exercise that produces significant acidosis warrants comprehensive study.6 While stacking some supplements may provide additional benefits, some athletes may not be aware that taking multiple supplement products creates the potential for doubling up on some ingredients or co-ingesting ingredients that are best not combined. Inadvertent or unintentional …
Effects of fluticasone propionate in COPD patients with bronchial hyperresponsiveness
Authors: G T Verhoeven
Journal: Thorax (2002)

<b>Background:</b> Treatment of chronic obstructive pulmonary disease (COPD) with inhaled corticosteroids does not appear to be as effective as similar treatment of asthma. It seems that only certain subgroups of patients with COPD benefit from steroid treatment. A study was undertaken to examine whether inhaled fluticasone propionate (FP) had an effect on lung function and on indices of inflammation in a subgroup of COPD patients with bronchial hyperresponsiveness (BHR). <b>Methods:</b> Twenty three patients with COPD were studied. Patients had to be persistent current smokers between 40 and 70 years of age. Non-specific BHR was defined as a PC<sub>20</sub> for histamine of ≤8 mg/ml. Patients received either 2 × 500 μg FP or placebo for 6 months. Expiratory volumes were measured at monthly visits, BHR was determined at the start of the study and after 3 and 6 months, and bronchial biopsy specimens were taken at the start and after 6 months of treatment. Biopsy specimens from asymptomatic smokers served as controls. <b>Results:</b> In contrast to asthma, indices of BHR were not significantly influenced by treatment with FP. Forced expiratory volume in 1 second (FEV<sub>1</sub>) showed a steep decline in the placebo group but remained stable in patients treated with FP. FEV<sub>1</sub>/FVC, and maximal expiratory flows at 50% and 25% FVC (MEF<sub>50</sub>, MEF<sub>25</sub>) were significantly increased in the FP treated patients compared with the placebo group. Biopsy specimens were analysed for the presence of CD3+, CD4+, CD8+, MBP+, CD15+, CD68+, CD1a, and tryptase cells. FP treatment resulted in marginal reductions in these indices of inflammation. <b>Conclusion:</b> In patients with COPD and BHR, FP has a positive effect on indices of lung function compared with placebo. Bronchial inflammation analysed in bronchial biopsy specimens is only marginally reduced.
Concurrent or sequential adjuvant letrozole and radiotherapy after conservative surgery for early-stage breast cancer (CO-HO-RT): a phase 2 randomised trial
Authors: David Azria, Yazid Belkacemi, Gilles Romieu, Sophie Gourgou, Marian Gutowski, Khalil Zaman, Carmen Llacer Moscardo, Claire Lemanski, Michael Coelho, Barry Rosenstein, Pascal Fenoglietto, Nigel EA Crompton, Mahmut Ozsahin
Journal: The Lancet Oncology (2010)
Which subgroup of patients with rheumatoid arthritis benefits from switching to rituximab versus alternative anti-tumour necrosis factor (TNF) agents after previous failure of an anti-TNF agent?
Authors: A Finckh, A Ciurea, L Brulhart, B Möller, U A Walker, D Courvoisier, D Kyburz, J Dudler, C Gabay
Journal: Annals of the Rheumatic Diseases (2009)

Background: Patients with rheumatoid arthritis (RA) with an inadequate response to TNF antagonists (aTNFs) may switch to an alternative aTNF or start treatment from a different class of drugs, such as rituximab (RTX). It remains unclear in which clinical settings these therapeutic strategies offer most benefit. Objective: To analyse the effectiveness of RTX versus alternative aTNFs on RA disease activity in different subgroups of patients. Methods: A prospective cohort study of patients with RA who discontinued at least one aTNF and subsequently received either RTX or an alternative aTNF, nested within the Swiss RA registry (SCQM-RA) was carried out. The primary outcome, longitudinal improvement in 28-joint count Disease Activity Score (DAS28), was analysed using multivariate regression models for longitudinal data and adjusted for potential confounders. Results: Of the 318 patients with RA included; 155 received RTX and 163 received an alternative aTNF. The relative benefit of RTX varied with the type of prior aTNF failure: when the motive for switching was ineffectiveness to previous aTNFs, the longitudinal improvement in DAS28 was significantly better with RTX than with an alternative aTNF (p = 0.03; at 6 months, −1.34 (95% CI −1.54 to −1.15) vs −0.93 (95% CI −1.28 to −0.59), respectively). When the motive for switching was other causes, the longitudinal improvement in DAS28 was similar for RTX and alternative aTNFs (p = 0.40). These results were not significantly modified by the number of previous aTNF failures, the type of aTNF switches, or the presence of co-treatment with a disease-modifying antirheumatic drug. Conclusion: This observational study suggests that in patients with RA who have stopped a previous aTNF treatment because of ineffectiveness changing to RTX is more effective than switching to an alternative aTNF.
Reduction of chemotherapy-induced febrile leucopenia by prophylactic use of ciprofloxacin and roxithromycin in small-cell lung cancer patients: An EORTC double-blind placebo-controlled phase III study
Authors: V.C.G. Tjan-Heijnen, P.E. Postmus, A. Ardizzoni, Ch. Manegold, J. Burghouts, J. van Meerbeeck, S. Gans, M. Mollers, E. Buchholz, B. Biesma, C. Legrand, C. Debruyne, G. Giaccone
Journal: Annals of Oncology (2001)
THE HUMAN HEALTH EFFECTS OF DDT (DICHLORODIPHENYLTRICHLOROETHANE) AND PCBS (POLYCHLORINATED BIPHENYLS) AND AN OVERVIEW OF ORGANOCHLORINES IN PUBLIC HEALTH
Authors: Matthew P. Longnecker, Walter J. Rogan, George Lucier
Journal: Annual Review of Public Health (1997)

Organochlorines are a diverse group of persistent synthetic compounds, some of which are detectable in nearly everyone. Many organochlorines are endocrine disruptors or carcinogens in experimental assays. p,p'-DDE (dichlorodiphenyl-dichloroethene) and PCBs (polychlorinated biphenyls) comprise the bulk of organochlorine residues in human tissues. We reviewed relevant human data cited in the 1991-1995 Medline database and elsewhere. High-level exposure to selected organochlorines appears to cause abnormalities of liver function, skin (chloracne), and the nervous system. Of more general interest, however, is evidence suggesting insidious effects of background exposure. Of particular concern is the finding of neonatal hypotonia or hyporeflexia in relation to PCB exposure. The epidemiologic data reviewed, considered in isolation, provide no convincing evidence that organochlorines cause a large excess number of cancers. A recent risk assessment that considered animal data, however, gives a cancer risk estimate for background exposure to dioxin and dioxin-like compounds (e.g. some PCBs) with an upper bound in the range of 10(-4) per year.
Provider Delay Among Patients With Breast Cancer in Germany: A Population-Based Study
Authors: Volker Arndt, Til Stürmer, Christa Stegmaier, Hartwig Ziegler, Annelie Becker, Hermann Brenner
Journal: Journal of Clinical Oncology (2003)

Purpose: Delaying the diagnosis and initiation of treatment of cancer is likely to result in tumor progression and a worse prognosis. We examined sources and consequences of provider delay among female breast cancer patients in a population-based study in Germany. Patients and Methods: Three hundred eighty women, who were ages 18 to 80 years and who had invasive breast cancer, were interviewed with respect to the diagnostic process. Provider delay was defined as time from first presentation to a health care provider until initiation of cancer treatment. Results: Median provider delay was 15 days and did not substantially differ by the specialty of first consulted physician. Delays in the diagnostic work-up were mainly because of erroneous initial suspicion of a benign breast disease or because of time constraints by patients or physicians. Provider delay over 3 months was found in 11% of all breast cancer cases and was associated with patient characteristics such as higher education (odds ratio [OR] = 2.6; 95% confidence interval [CI], 1.3 to 5.4), full-time employment (OR = 2.5; 95% CI, 1.1 to 5.5), family history of breast cancer (OR = 2.8; 95% CI, 1.2 to 6.2), and presenting with a non–breast symptom (OR = 4.3; 95% CI, 1.7 to 10.9). The association between duration of diagnostic work-up and stage at diagnosis was U shaped, with the highest proportions of metastasized breast cancer tumors among women with very short (&lt; 7 days) or very long (&gt; 3 months) duration. Conclusion: Diagnostic work-up is within reasonably short time limits among most patients with breast cancer in Germany. Although the association between delay and tumor stage seems to be complex, any delay in diagnostic work-up should be kept to a minimum.
Sofosbuvir (GS-7977) plus peginterferon/ribavirin in treatment-naïve patients with HCV genotype 1: A randomized, 28-day, dose-ranging trial
Authors: Maribel Rodriguez-Torres, Eric Lawitz, Kris V. Kowdley, David R. Nelson, Edwin DeJesus, John G. McHutchison, Melanie T. Cornpropst, Michael Mader, Efsevia Albanis, Deyuan Jiang, Christy M. Hebner, William T. Symonds, Michelle M. Berrey, Jay Lalezari
Journal: Journal of Hepatology (2012)
High Rates of Durable Responses With Anti-CD22 Fractionated Radioimmunotherapy: Results of a Multicenter, Phase I/II Study in Non-Hodgkin's Lymphoma
Authors: Franck Morschhauser, Françoise Kraeber-Bodéré, William A. Wegener, Jean-Luc Harousseau, Marie-Odile Petillon, Damien Huglo, Lorenz H. Trümper, Johannes Meller, Michael Pfreundschuh, Carl-Martin Kirsch, Ralph Naumann, Joachim Kropp, Heather Horne, Nick Teoh, Steven Le Gouill, Caroline Bodet-Milin, Jean-Francois Chatal, David M. Goldenberg
Journal: Journal of Clinical Oncology (2010)

Purpose Fractionated radioimmunotherapy targeting CD22 may substantially improve responses and outcome in non-Hodgkin's lymphoma (NHL). Patients and Methods A multicenter trial evaluated two or three weekly infusions of yttrium-90 ( 90 Y) epratuzumab tetraxetan (humanized anti-CD22 antibody) in 64 patients with relapsed/refractory NHL, including 17 patients who underwent prior autologous stem-cell transplantation (ASCT). Objective (OR) and complete responses (CR/complete response unconfirmed [CRu]), as well as progression-free survival (PFS), were determined. Results At the maximum total 90 Y dose of 45 mCi/m 2 (1,665 MBq/m 2 ), grade 3 to 4 hematologic toxicities were reversible to grade 1 in patients with less than 25% bone marrow involvement. The overall OR rate and median PFS for all 61 evaluable patients was 62% (CR/CRu, 48%) and 9.5 months, respectively. Patients without prior ASCT obtained high OR rates of 71% (CR/CRu, 55%) across all NHL subtypes and 90 Y doses, even in poor-risk categories (refractory to last anti-CD20–containing regimen, 73% [CR/CRu, 60%]; bulky disease: 71% [CR/CRu, 43%]). Patients with prior ASCT received lower doses, but achieved an OR rate of 41% (CR/CRu, 29%). For patients with follicular lymphoma (FL), OR rates and median PFS increased with total 90 Y-dose, reaching 100% (CR/CRu, 92%) and 24.6 months, respectively, at the highest dose levels (&gt; 30 mCi/m 2 total 90 Y-dose [1,110 MBq/m 2 ]). Further, patients with FL refractory to prior anti-CD20–containing regimens achieved 90% (nine of 10 patients) OR and CR/CRu rates and a median PFS of 21.5 months. Conclusion Fractionated anti-CD22 radioimmunotherapy provides high total doses of 90 Y, yielding high rates of durable CR/CRus in relapsed/refractory NHL, resulting in 20 mCi/m 2 × 2 weeks as the recommended dose for future studies.
Effect of maternal asthma, exacerbations and asthma medication use on congenital malformations in offspring: a UK population-based study
Authors: L J Tata, S A Lewis, T M McKeever, C J P Smith, P Doyle, L Smeeth, J E Gibson, R B Hubbard
Journal: Thorax (2008)

<h3>Background:</h3> Clinical advice to pregnant women with asthma is to maintain optimal therapeutic management; however, potential adverse effects of asthma treatments on fetal development remain uncertain. A study was undertaken to assess the association between maternal asthma and gestational exposure to asthma medications with risk of congenital malformation in offspring. <h3>Methods:</h3> A matched case-control study was performed using The Health Improvement Network primary care database. Children with malformations were matched to control children on birth year, general practice and singleton or twin delivery. <h3>Results:</h3> 5124 cases of liveborn children with major congenital malformations and 30 053 controls were included in the study. The risk of any malformation in children born to women with asthma was marginally higher than that in children born to women without asthma (adjusted OR 1.10, 95% CI 1.01 to 1.20). However, no association was present in children born to mothers receiving asthma treatment in the year before or during pregnancy (OR 1.06, 95% CI 0.94 to 1.20). In assessing teratogenicity of medications, no increased risk of malformation was found with gestational exposures to short- or long-acting β agonists, inhaled corticosteroids, oral corticosteroids, other bronchodilators or cromones. These findings were similar for each of 11 system-specific malformation groups, except for an increase in musculo-skeletal system malformation associated with cromone exposure. <h3>Conclusions:</h3> Gestational exposure to commonly used asthma medications was found to be safe overall, although a moderate teratogenic risk of cromones cannot be excluded. There was some evidence of a small increased risk of congenital malformation in children born to women with asthma, but this was not explained by gestational exposure to asthma drugs.
An important role of matrix metalloproteinase-8 in angiogenesis in vitro and in vivo
Authors: Changcun Fang, Guanmei Wen, Li Zhang, Luyang Lin, Andrew Moore, Shuming Wu, Shu Ye, Qingzhong Xiao
Journal: Cardiovascular Research (2013)

Growing evidence suggests a close association of plaque angiogenesis with atherosclerotic plaque formation and progression, and an important role of matrix metalloproteinase (MMP) in angiogenesis and atherosclerosis. We attempted to investigate the functional involvements of MMP8 in angiogenesis. Knockdown of MMP8 in human umbilical vein endothelial cells (HuVECs) with MMP-8 shRNA lentivirus resulted in a decrease in in vitro capillary-like network formation, cell proliferation and migration, and impaired its capacity of in vivo angiogenesis. Less nuclear accumulation of β-catenin and lower β-catenin target gene expression levels was observed in the HuVECs expressing lower levels of endogenous MMP8. Knockdown of endogenous MMP8 in HuVECs down-regulated platelet/endothelial cell adhesion molecule-1 (PECAM-1) expression by converting less angiotensin I to II, which is an inducer for PECAM-1 gene expression. Aortic rings isolated from MMP8−/−/apoE−/− mice had less endothelial cell sprouting, and endothelial cells in MMP8−/−/apoE−/− mice had a lower ability to migrate into Matrigel plugs and less capacity of proliferation and angiogenesis. Moreover, immunohistochemical analyses revealed that MMP8 was expressed in microvessels within human atherosclerotic plaques and aneurysm. Finally, analyses of MMP8−/−/apoE−/− and MMP8+/+/apoE−/− mice fed a Western diet for 12 weeks showed that MMP8-deficient mice had small lesion size and less endothelial cells within atherosclerotic lesions. We demonstrated for the first time that MMP8 plays an important role in angiogenesis in vitro and in vivo. Our findings provide new insights into the molecular mechanisms of plaque angiogenesis and suggest that MMP8 is a potential therapeutic target of cardiovascular diseases.