tbuckley/cabot-search huggingface dataset:
High-intensity versus low-intensity non-invasive ventilation in patients with stable hypercapnic COPD: a randomised crossover trial
Authors: M. Dreher, J. H Storre, C. Schmoor, W. Windisch
Journal: Thorax (2010)

<h3>Rationale</h3> The conventional approach of low-intensity non-invasive positive pressure ventilation (NPPV) produces only minimal physiological and clinical benefits in patients with stable hypercapnic chronic obstructive pulmonary disease (COPD). <h3>Objectives</h3> To determine whether the novel approach of high-intensity NPPV is superior to low-intensity NPPV in controlling nocturnal hypoventilation. <h3>Methods</h3> A randomised controlled crossover trial comparing 6 weeks of high-intensity NPPV (using controlled ventilation with mean inspiratory pressures of 28.6±1.9 mbar) with low-intensity NPPV (using assisted ventilation with mean inspiratory pressures of 14.6±0.8 mbar) was performed in 17 patients with severe stable hypercapnic COPD. <h3>Results</h3> Two patients refused low-intensity NPPV and two patients dropped out while on low-intensity NPPV. Thirteen patients (mean forced expiratory volume in 1 s (FEV<sub>1</sub>) 0.76±0.29 l) completed the trial. High-intensity NPPV produced higher pneumotachographically-measured expiratory volumes, with a mean treatment effect of 96 ml (95% CI 23 to 169) (p=0.015). This resulted in a mean treatment effect on nocturnal arterial carbon dioxide tension (Paco<sub>2</sub>) of −9.2 mm Hg (95% CI −13.7 to −4.6) (p=0.001) in favour of high-intensity NPPV. Daily use of NPPV was increased in high-intensity NPPV compared with low-intensity NPPV, with a mean difference of 3.6 h/day (95% CI 0.6 to 6.7) (p=0.024). In addition, compared with baseline, only high-intensity NPPV resulted in significant improvements in exercise-related dyspnoea, daytime Paco<sub>2</sub>, FEV<sub>1</sub>, vital capacity and the Severe Respiratory Insufficiency Questionnaire Summary Score. <h3>Conclusions</h3> High-intensity NPPV is better tolerated by patients with severe chronic hypercapnic COPD and has been shown to be superior to the conventional and widely-used form of low-intensity NPPV in controlling nocturnal hypoventilation. High-intensity NPPV therefore offers a new promising therapeutic option for these patients.
Identification and characterization of a very low density lipoprotein receptor-binding peptide from tissue factor pathway inhibitor that has antitumor and antiangiogenic activity
Authors: Todd A. Hembrough, Jose F. Ruiz, Bonnie M. Swerdlow, Glenn M. Swartz, Hans J. Hammers, Li Zhang, Stacy M. Plum, Mark S. Williams, Dudley K. Strickland, Victor S. Pribluda
Journal: Blood (2004)
Monocytes Heterozygous for the Asp299Gly and Thr399Ile Mutations in the Toll-like Receptor 4 Gene Show No Deficit in Lipopolysaccharide Signalling
Authors: Clett Erridge, John Stewart, Ian R. Poxton
Journal: The Journal of Experimental Medicine (2003)

Toll-like receptor 4 (TLR4)-mediated recognition of lipopolysaccharide (LPS) is required for efficient recognition of Gram-negative bacterial infections. Two commonly occurring mutations in the human TLR4 gene (Asp299Gly and Thr399Ile) have recently been shown to be associated with blunted physiological responses to inhaled LPS, and with increased risk of Gram-negative bacteraemia in sepsis patients and reduced risk of atherosclerosis in an Italian population. Here we show that monocytes from individuals heterozygous for both mutations in the TLR4 gene exhibit no deficit in recognition of LPS of Escherichia coli, Neisseria meningitidis, Bacteroides fragilis, Yersinia pestis, Chlamydia trachomatis, Porphyromonas gingivalis, or Pseudomonas aeruginosa. We propose that the relatively high frequency of these mutations in the Caucasian population may reflect modified responses of carriers to alternative TLR4 agonists.
HGF/c-Met Acts as an Alternative Angiogenic Pathway in Sunitinib-Resistant Tumors
Authors: Farbod Shojaei, Joseph H. Lee, Brett H. Simmons, Anthony Wong, Carlos O. Esparza, Pamela A. Plumlee, Junli Feng, Albert E. Stewart, Dana D. Hu-Lowe, James G. Christensen
Journal: Cancer Research (2010)

Molecular and cellular mechanisms underlying resistance/low responsiveness to antiangiogenic compounds are under extensive investigations. Both populations of tumor and stroma (nontumor compartment) seem to contribute in inherent/acquired resistance to antiangiogenic therapy. Here, investigating in vivo efficacy of sunitinib in experimental models resulted in the identification of tumors that were resistant/sensitive to the therapy. Analysis of tumor protein lysates indicated a greater concentration of hepatocyte growth factor (HGF) in resistant tumors than in sensitive ones. In addition, using flow cytometry, c-Met expression was found to be significantly higher in endothelial cells than in tumor cells, suggesting that HGF might target the vascular endothelial cells in resistant tumors. Combination of sunitinib and a selective c-Met inhibitor significantly inhibited tumor growth compared with sunitinib or c-Met inhibitor alone in resistant tumors. Histology and in vitro analyses suggested that combination treatment mainly targeted the vasculature in the resistant tumors. Conversely, systemic injection of HGF in the sensitive tumor models conferred resistance to sunitinib through maintenance of tumor angiogenesis. In conclusion, our study indicates a role for HGF/c-Met pathway in development of resistance to antiangiogenic therapy and suggests a potential strategy to circumvent resistance to vascular endothelial growth factor receptor tyrosine kinase inhibitor in the clinic.
Infection and Atherosclerosis
Authors: Stephen E. Epstein, Yi Fu Zhou, Jianhui Zhu
Journal: Circulation (1999)

Abstract —Although definitive proof of a causal role of infection contributing to atherogenesis is lacking, multiple investigations have demonstrated that infectious agents evoke cellular and molecular changes supportive of such a role. Moreover, both Chlamydia pneumoniae and cytomegalovirus exacerbate lesion development in animal models of atherosclerosis and restenosis. The fact that multiple pathogens have been associated with atherosclerosis implies that many “atherogenic” pathogens exist, and recent data suggest that the risk of atherosclerosis conveyed by infection relates to the number of atherogenic pathogens with which an individual is infected. It also is evident that variability in host susceptibility to the atherogenic effects of pathogens exists; this variability appears to be related at least in part to whether the host can generate an immune response that successfully controls pathogen inflammatory activity and in part to the specific pattern of immune response—humoral or cellular. The latter may relate to host capacity to control pathogen activity and to a pathogen-induced autoimmune component of the atherogenic process. Additional animal and human studies are necessary to further test the validity of the infection/atherosclerosis link and to provide more insight into the mechanisms by which infection may contribute to atherosclerosis, information critical for devising strategies to reduce or eliminate any contribution to atherosclerosis caused by infection.
Transgenic Overexpression of Constitutively Active Protein Kinase C ε Causes Concentric Cardiac Hypertrophy
Authors: Yasuchika Takeishi, Peipei Ping, Roberto Bolli, Darryl L. Kirkpatrick, Brian D. Hoit, Richard A. Walsh
Journal: Circulation Research (2000)

Abstract —To test the hypothesis that activation of the protein kinase C (PKC) ε isoform leads to cardiac hypertrophy without failure, we studied transgenic mice with cardiac-specific overexpression of a constitutively active mutant of the PKCε isoform driven by an α–myosin heavy chain promoter. In transgenic mice, the protein level of PKCε in heart tissue was increased 9-fold. There was a 6-fold increase of the membrane/cytosol ratio, and PKC activity in the membrane fraction was 4.2-fold compared with wild-type mice. The heart weight was increased by 28%, and upregulation of the mRNA for β-myosin heavy chain and α-skeletal actin was observed in transgenic mouse hearts. Echocardiography demonstrated increased anterior and posterior wall thickness with normal left ventricular function and dimensions, indicating concentric cardiac hypertrophy. Isolated cardiomyocyte mechanical function was slightly decreased, and Ca 2+ signals were markedly depressed in transgenic mice, suggesting that myofilament sensitivity to Ca 2+ was increased. No differences were observed in either the levels of cardiac Ca 2+ -handling proteins or the degree of cardiac regulatory protein phosphorylation between wild-type and transgenic mice. Unlike mice with PKCβ 2 overexpression, transgenic mice with cardiac-specific overexpression of the active PKCε mutant demonstrated concentric hypertrophy with normal in vivo cardiac function. Thus, PKC isoforms may play differential functional roles in cardiac hypertrophy and failure.
<i>miR-152</i> Is a Tumor Suppressor microRNA That Is Silenced by DNA Hypermethylation in Endometrial Cancer
Authors: Tomohiko Tsuruta, Ken-ichi Kozaki, Atsushi Uesugi, Mayuko Furuta, Akira Hirasawa, Issei Imoto, Nobuyuki Susumu, Daisuke Aoki, Johji Inazawa
Journal: Cancer Research (2011)

The etiology and development of human cancers that remain little understood might be enlightened by defining tumor suppressor microRNAs (TS-miRNA). In this study, we identified TS-miRNAs silenced by aberrant DNA hypermethylation in endometrial cancer. Functional screening of 327 synthetic miRNAs in an endometrial cancer cell proliferation assay identified 103 miRNAs that inhibited cell growth. We then determined the sequence, DNA methylation status, and expression levels of these miRNAs in endometrial cancer cell lines and primary tumors. These determinations led to the identification of miR-152 as a candidate TS-miRNA gene in endometrial cancer. Epigenetic silencing documented in miR-152 was consistent with its location at 17q21.32 in intron 1 of the COPZ2 gene, which is also silenced often in endometrial cancer by DNA hypermethylation, and also with evidence that miR-152 targets the DNA methyltransferase DNMT1. Notably, restoration of miR-152 expression in endometrial cancer cell lines was sufficient to inhibit tumor cell growth in vitro and in vivo. We identified E2F3, MET, and Rictor as novel candidate targets of miR-152, suggesting how its epigenetic silencing can drive endometrial carcinogenesis. Our findings define a central role for miR-152 in endometrial cancer, and they also suggest its use in new therapeutic strategies to treat this cancer.
Evaluation of the antismoking therapy within two specialized medical practice – Arges county
Authors: Razvan Marmandiu, Loredana Marmandiu, Cristian Didilescu
Journal: European Respiratory Journal (2011)

Objective:  Evaluation of the abstinence rate for 1956 people who were administered pharmacological treatment combined with psychological support within the programme “Stop-Smoking” in 2 medical practice within Arges County, August 2008-March2010.   Methods:  The initiantion, clinical check and final evaluation were based on standard forms within this programme. One carried out nicotine addiction, clinical status and existing comorbidities, CO exahaled. Three types of treatment were offers for free with psychological support. The final evaluation was carried out 6 months later.   Results:  Treatment based on nicotine patches was administered to patients with low and medium nicotine addiction and to those who had contraindications for others therapies. For a number of 140 patients treated in this way, the abstinence rate was of 34.29%. Treatment on bupropion was administered to a number of 1360 patients with different nicotine addiction degrees, from low to severe. Abstinence rate for the group with Bupropion was 35.96%. Treatment based on varenicline was administered predominantly to patients with severe nicotine addiction, to old people or important comorbidities. for a number of 456 patients treated with varenicline, the abstinence rate was 46.27%.   Conclusions:  The results confirm the pharmacological therapy combined with psychological support as an important method to obtain superior results compared with the lack of assistance in the attemp to give up smoking or antismoking counselling only. The abstinence rate was of 37.91% for all types of pharmacological treatment combined with psycological support.
Nonadipose tissue production of leptin: Leptin as a novel placenta-derived hormone in humans
Authors: Hiroaki Masuzaki, Yoshihiro Ogawa, Norimasa Sagawa, Kiminori Hosoda, Tsunekazu Matsumoto, Hiroko Mise, Haruo Nishimura, Yaunao Yoshimasa, Issei Tanaka, Takahide Mori, Kazuwa Nakao
Journal: Nature Medicine (1997)
Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Pathway and Its Therapeutic Implications
Authors: Elisabeth G.E. de Vries, Jourik A. Gietema, Steven de Jong
Journal: Clinical Cancer Research (2006)

Apoptosis can be executed through a mitochondria-dependent (intrinsic) and a death receptor–dependent, mitochondria-independent (extrinsic) pathway. The intrinsic pathway is initiated by, for example, chemotherapy and/or radiotherapy, and the extrinsic pathway is initiated by ligand-induced
Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial
Authors: Roger Stupp, Monika E Hegi, Thierry Gorlia, Sara C Erridge, James Perry, Yong-Kil Hong, Kenneth D Aldape, Benoit Lhermitte, Torsten Pietsch, Danica Grujicic, Joachim Peter Steinbach, Wolfgang Wick, Rafał Tarnawski, Do-Hyun Nam, Peter Hau, Astrid Weyerbrock, Martin J B Taphoorn, Chiung-Chyi Shen, Nalini Rao, László Thurzo, Ulrich Herrlinger, Tejpal Gupta, Rolf-Dieter Kortmann, Krystyna Adamska, Catherine McBain, Alba A Brandes, Joerg Christian Tonn, Oliver Schnell, Thomas Wiegel, Chae-Yong Kim, Louis Burt Nabors, David A Reardon, Martin J van den Bent, Christine Hicking, Andriy Markivskyy, Martin Picard, Michael Weller
Journal: The Lancet Oncology (2014)
Author response to van Zuuren<i>et al</i>., Penicillin to prevent recurrent cellulitis: a critical appraisal
Authors: K.S. Thomas
Journal: British Journal of Dermatology (2014)

Journal Article Author response to van Zuuren et al., Penicillin to prevent recurrent cellulitis: a critical appraisal Get access K.S. Thomas, K.S. Thomas Centre of Evidence Based Dermatology University of Nottingham Nottingham NG7 2NR U.K Search for other works by this author on: Oxford Academic Google Scholar on behalf of the PATCH I trial team on behalf of the PATCH I trial team Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 171, Issue 6, 1 December 2014, Pages 1303–1304, https://doi.org/10.1111/bjd.13554 Published: 01 December 2014
Normothermic perfusion of donor lungs for preservation and assessment with the Organ Care System Lung before bilateral transplantation: a pilot study of 12 patients
Authors: Gregor Warnecke, Javier Moradiellos, Igor Tudorache, Christian Kühn, Murat Avsar, Bettina Wiegmann, Wiebke Sommer, Fabio Ius, Claudia Kunze, Jens Gottlieb, Andres Varela, Axel Haverich
Journal: The Lancet (2012)
Angiotensin converting enzyme in human synovium: increased stromal [125I]351A binding in rheumatoid arthritis
Authors: D. A. Walsh
Journal: Annals of the Rheumatic Diseases (2000)

To determine whether tissue angiotensin converting enzyme (ACE) is increased in synovia from patients with rheumatoid arthritis, osteoarthritis or chondromalacia patellae.Sections of synovia from patients with rheumatoid arthritis (n = 7), osteoarthritis (n = 7) or chondromalacia patellae (n = 6) were tested for immunoreactivity for ACE, and for binding of the ACE inhibitor [(125)I]351A. The amount of ACE was measured with computer assisted image analysis as the proportion of synovial section area occupied by ACE-immunoreactive cells, and the density of [(125)I]351A binding.[(125)I]351A binding sites had characteristics of ACE and colocalised with ACE-like immunoreactivity to microvascular endothelium and fibroblast-like stromal cells in inflamed and non-inflamed human synovium. Stromal [(125)I]351A binding densities (B(eq)) and the fraction of synovial section area occupied by ACE-immunoreactivity (fractional area) were higher in synovia from patients with rheumatoid arthritis (B(eq) 28 amol/mm(2), fractional area 0.21) than from those with osteoarthritis (B(eq) 9 amol/mm(2), fractional area 0.10) or chondromalacia patellae (B(eq) 9 amol/mm(2), fractional area 0.09)(p < 0.05). Density of [(125)I]351A binding to stroma was similar to that to blood vessels in rheumatoid arthritis, but less dense than vascular binding in chondromalacia patellae and osteoarthritis. Increases in [(125)I]351A binding densities were attributable to increases in the numbers of binding sites, and were consistent with an increase in the density of ACE bearing stromal cells.ACE is upregulated in synovial stroma in rheumatoid arthritis. Increased tissue ACE may result in increased local generation of the vasoconstrictor and mitogenic peptide angiotensin II and thereby potentiate synovial hypoxia and proliferation in rheumatoid arthritis.
Doctor's Orders
Authors: Robert M. Veatch
Journal: JAMA (1985)

The "do not resuscitate" (DNR) order has become an important phenomenon in the evolution of more responsive and humane care of critically and terminally ill patients. Guidelines for decisions pertaining to resuscitation have been developed and are the source of much research,<sup>1,2</sup>therapeutic discussion,<sup>3,4</sup>and policy debate.<sup>5</sup> Underlying these discussions about decisions to forego resuscitation and a whole range of other decisions in the medical sphere is a broader conceptual problem: the problem of the metaphor of<i>orders</i>. What is going on when an institution as important as health care chooses the image of order giver? At the same time, society and the health professions alike are moving toward a consensual or covenantal model in which the patient makes choices with the support of significant others including family, friends, clergy, and health care professionals. Is the language of order giver compatible with these new, exciting developments that signal
<i>ABCC2</i> and Clinical Outcome of Tamoxifen Therapy
Authors: Thomas Lang, Werner Schroth, Hiltrud Brauch, Matthias Schwab
Journal: Journal of Clinical Oncology (2010)

TO THE EDITOR: The study by Kiyotani et al is another important contribution to the field of tamoxifen (TAM) pharmacogenomics in favor of CYP2D6 genetic testing for the improvement of TAM response in postmenopausal Japanese patients with breast cancer. In addition, for the first time, the authors identified a significant association between the rs3740065 G allele (intron 29, IVS29 154A G) of the ABC efflux drug transporter ABCC2 (multidrug related protein [MRP2]) and longer recurrence-free survival compared with individuals carrying the A allele in their study population of 282 patients. Because TAM-resistant MCF-7 cells express higher levels of ABCC2 than nonresistant MCF-7 cells, it has been suggested that ABCC2 induction could play a role in TAM resistance. On these grounds, Kiyotani et al speculated that the rs3740065 variant may be associated with increased ABCC2 expression and enhanced transport activity, thereby lowering the exposure of breast cancer cells to endoxifen, the active metabolite of TAM. However, in their study, the G allele was associated with longer recurrence-free survival, which would rather indicate a lower expression of ABCC2 and, hence, reduced transporter activity in breast cancer cells, resulting in higher intracellular endoxifen levels. Recently, a systematic DNA sequencing study that included 236 healthy individuals of Japanese ethnic background showed that a common promoter variant in ABCC2 ( 1774delG) is in strong linkage disequilibrium with rs3740065. Moreover, functional studies revealed that the 1774delG variation decreased ABCC2 promoter activity by 36% and that the promoter carrying the 1774delG allele had a defect in chenodeoxycholic acid–induced induction of promoter activity. Finally, a haplotype containing the 1774delG polymorphism showed a strong association with cholestatic or mixedtype hepatitis. We, therefore, propose that it is the 1774delG variant that can explain the findings of an association between ABCC2 and TAM outcome reported by Kiyotani et al. Unfortunately, the authors did not include the 1774delG variant in their investigation. Therefore, the issue of ABCC2 variants that predict clinical outcome must await more specific studies.
Dissecting complex traits: recent advances in hypertension genomics
Authors: Kevin M O'Shaughnessy
Journal: Genome Medicine (2009)

Genome-wide association scans are beginning to identify risk alleles for a number of complex diseases and traits. Essential hypertension looked as though it would be an exception to this trend after the Wellcome Trust Case Control Consortium data were published in 2007. However, more recent scans and meta-analyses have reversed the fortunes of essential hypertension. A number of loci have been identified, including a new antihypertensive drug target in the guise of the serine/threonine kinase SPAK. This kinase forms part of a novel kinase cascade that regulates the NCCT (Na+/Cl- co-transporter; SLC12A3) in the kidney and is defective in a rare Mendelian hypertension syndrome (Gordon's syndrome). Genome-wide scans are also being used to look for alleles to predict individual response to antihypertensive drugs and their risk of causing side-effects. The results of these are expected in the near future and may finally deliver the long-awaited goal of personalized drug therapy for hypertensive patients.
Dangerous liaisons at the virological synapse
Authors: Vincent Piguet, Quentin Sattentau
Journal: Journal of Clinical Investigation (2004)

Cell-to-cell viral transmission facilitates the propagation of HIV-1 and human T cell leukemia virus type 1. Mechanisms of cell-to-cell transmission by retroviruses were not well understood until the recent description of virological synapses (VSs). VSs function as specialized sites of immune cell-to-cell contact that direct virus infection. Deciphering the molecular mechanisms of VS formation provides a fascinating insight into how pathogens subvert immune cell communication programs and achieve viral spread.
The Commonest Lumbar Disc--L.3!
Authors: George Gregg
Journal: British Journal of Sports Medicine (1974)

A very large proportion of patients referred to my Department of Physical Medicine from General Practitioners, Medical and Surgical colleagues, complain of low back pain with or without leg signs and symptoms.This has commonly been attributed to sciatica.More and more, however, I came to think that some hitherto unsuspected factor was involved.