tbuckley/cabot-search huggingface dataset:
PTU-007 Cerebral oedema is rare in acute-on-chronic liver failure
Authors: D Joshi, A Patel, J O'Grady, D Shawcross, S Connors, C Willars, W Bernal, J Wendon, G Auzinger
Journal: Gut (2012)

<h3>Introduction</h3> Acute-on-chronic liver failure (AoCLF) has a rapidly progressive disease course associated with significant mortality. Hepatic encephalopathy (HE) is common associated with hyperammonemia, systemic inflammation and hyponatremia. The prevalence of cerebral oedema in AoCLF is unknown. We aimed to describe the prevalence of cerebral oedema in a cohort of AoCLF adult (&gt;18 years) patients admitted to the liver intensive treatment unit (LITU) between January 2005 and 2011. <h3>Methods</h3> AoCLF was defined using criteria of Sarin <i>et al</i>.<sup>1</sup> Arterial ammonia (NH3), MELD, UKELD, and organ failure (SOFA) scores were collated (results expressed as medians with ranges). Patients who had undergone cranial CT imaging were identified. Neuro-images were reported by consultant neuro-radiologists. <h3>Results</h3> During the study period, 1008 patients with chronic liver disease (CLD) were admitted to the LITU. 173 patients (110 male) underwent neuro-imaging. Of these 81 (48 male) fulfilled criteria for AoCLF, Over the same time period 655 patients were admitted with acute liver failure. Variceal bleeding (30%) and sepsis (31%) were the most frequent precipitants of AoCLF. Compared to the CLD group, AoCLF patients were younger (50, 24–71 vs 59, 30–74, p=0.001), serum NH3 (143, 40–305 vs 111, 28–315), grade of HE (3, 1–4 vs 1, 0–4), MELD (25, 8–40 vs 15, 6–34), SOFA (11, 2–17 vs 4, 0–14), UKELD (63, 50–75 vs 55, 44–73) and SIRS score (2, 1–3 vs 1, 0–3) were higher (p&lt;0.0001 for all). Serum sodium was lower in the AoCLF group (132 118–154 vs 136 120–146, p&lt;0.0001). HE (≥grade 3) occurred in 66% of AoCLF patients vs 13% CLD (p&lt;0.0001). In those with neuro-imaging, 26% were normal, 26% demonstrated increased cerebral atrophy for age, 15% small vessel disease and 10% intra-cranial haemorrhage. Cerebral oedema was seen in two patients with AoCLF, 1 post TIPSS (NH3 289 μmol/l) and 1 with septic shock (NH3 268 μmol/l). 72 patients with ALF underwent neuro-imaging with 32% showing radiological evidence of cerebral oedema. Compared to the CLD group, 30 and 90 day survival was poorer in AoCLF (52% and 42% vs 80% and 75%, log rank p&lt;0.0001). The mode of death was that of progressive multi-organ failure (MOF). The two patients with cerebral oedema on CT suffered cerebral deaths with tonsillar herniation. AUROC analysis for survival of AoCLF identified SOFA (0.67, 95% CI 0.54 to 0.8, p=0.02) MELD (0.74, 95% CI 0.61 to 0.87, p&lt;0.0001) and UKELD (0.87, 95% CI 0.8 to 0.97, p&lt;0.0001). <h3>Conclusion</h3> Our data demonstrates poor outcome in patients with AoCLF compared to those with CLD requiring admission to LITU. Mortality was attributable to MOF and although deep levels of encephalopathy requiring ventilation were common (66%), the prevalence of cerebral oedema was rare at 2%. <h3>Competing interests</h3> None declared. <h3>Reference</h3> 1. <b>Sarin</b>, <i>et al</i>. <i>Hep Int</i> 2009.
A REPLY to the ACCUSATIONS MADE by Mr. LEONARD HILL Against the HYDERABAD CHLOROFORM COMMISSION
Authors: T. L. Brunton
Journal: BMJ (1898)

joint may gradually acquire a great degree of compensatory movement.I ately saw a man aged I9, whose ankle-joint, after urethral arthritis, had become ankylosed in a position of rectangular talipes, but who, owing to the increased movement in the mediotarsal joint, walked without appre- ciable defect.
Activity of ciprofloxacin and levofloxacin in experimental pneumonia caused by Klebsiella pneumoniae deficient in porins, expressing active efflux and producing QnrA1
Authors: J.M. Rodríguez-Martínez, C. Pichardo, I. García, M.E. Pachón-Ibañez, F. Docobo-Pérez, A. Pascual, J. Pachón, L. Martínez-Martínez
Journal: Clinical Microbiology and Infection (2008)
France urged to close high risk operating theatres
Authors: Brad Spurgeon
Journal: BMJ (2006)

A report commissioned by the French health ministry has recommended the immediate closure of operating theatres in 113 small public hospitals around the country.

Patients having surgery in these small hospitals are at risk, the report said, because they have poor facilities and their surgical teams lack appropriate experience as they do not operate often enough.

The findings of the report, written by Dr Guy Vallancien, secretary general of the National Surgical Council, a health ministry advisory group, were made public last week by the daily newspaper Le Monde .

“Certain local …
Cytokines in Chronic Rhinosinusitis. Role in Eosinophilia and Aspirin-exacerbated Respiratory Disease
Authors: Whitney W. Stevens, Christopher J. Ocampo, Sergejs Berdnikovs, Masafumi Sakashita, Mahboobeh Mahdavinia, Lydia Suh, Tetsuji Takabayashi, James E. Norton, Kathryn E. Hulse, David B. Conley, Rakesh K. Chandra, Bruce K. Tan, Anju T. Peters, Leslie C. Grammer, Atsushi Kato, Kathleen E. Harris, Roderick G. Carter, Shigeharu Fujieda, Robert C. Kern, Robert P. Schleimer
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

The mechanisms that underlie the pathogenesis of chronic rhinosinusitis without nasal polyps (CRSsNP), chronic rhinosinusitis with nasal polyps (CRSwNP), and aspirin-exacerbated respiratory disease (AERD) are not clear.To first evaluate the inflammatory profiles of CRSsNP and CRSwNP tissues and then to investigate whether clinical differences observed between CRSwNP and AERD are in part secondary to differences in inflammatory mediator expression within nasal polyp (NP) tissues.Expression levels of numerous inflammatory mediators were determined by quantitative real-time polymerase chain reaction, ELISA, and multiplex immunoassay.CRSwNP NP had increased levels of type 2 mediators, including IL-5 (P < 0.001), IL-13 (P < 0.001), eotaxin-2 (P < 0.001), and monocyte chemoattractant protein (MCP)-4 (P < 0.01), compared with sinonasal tissue from subjects with CRSsNP and control subjects. Expression of IFN-γ messenger RNA or protein was low and not different among the chronic rhinosinusitis subtypes examined. Compared with CRSwNP, AERD NP had elevated protein levels of eosinophil cationic protein (ECP) (P < 0.001), granulocyte-macrophage colony-stimulating factor (GM-CSF) (P < 0.01), and MCP-1 (P = 0.01), as well as decreased gene expression of tissue plasminogen activator (tPA) (P = 0.02). Despite the higher eosinophilia in AERD, there was no associated increase in type 2 mediator protein levels observed.CRSwNP was characterized by a predominant type 2 inflammatory environment, whereas CRSsNP did not reflect a classic type 1 milieu, as has been suggested previously. AERD can be distinguished from CRSwNP by elevated ECP levels, but this enhanced eosinophilia is not associated with elevations in traditional type 2 inflammatory mediators associated with eosinophil proliferation and recruitment. However, other factors, including GM-CSF, MCP-1, and tPA, may be important contributors to AERD pathogenesis.
Home Endotoxin Exposure and Wheeze in Infants: Correction for Bias Due to Exposure Measurement Error
Authors: Nora Horick, Edie Weller, Donald K. Milton, Diane R. Gold, Ruifeng Li, Donna Spiegelman
Journal: Environmental Health Perspectives (2005)

Exposure to elevated levels of endotoxin in family-room dust was previously observed to be significantly associated with increased wheeze in the first year of life among a cohort of 404 children in the Boston, Massachusetts, metropolitan area. However, it is likely that family-room dust endotoxin was a surrogate for airborne endotoxin exposure. Therefore, a related substudy characterized the relationship between levels of airborne household endotoxin and the level of endotoxin present in house dust, in addition to identifying other significant predictors of airborne endotoxin in the home. We now reexamine the relationship between endotoxin exposure and wheeze under the assumption that the level of airborne endotoxin in the home is the exposure of interest and that the amount of endotoxin in household dust is a surrogate for this exposure. We applied a measurement error correction technique, using all available data to estimate the effect of endotoxin exposure in terms of airborne concentration and accounting for the measurement error induced by using house-dust endotoxin as a surrogate measure in the portion of the data in which airborne endotoxin could not be directly measured. After adjusting for confounding by lower respiratory infection status and race/ethnicity, endotoxin exposure was found to be significantly associated with a nearly 6-fold increase in prevalence of wheeze for a one interquartile range increase in airborne endotoxin (95% confidence interval, 1.2–26) among the 360 children in households with dust endotoxin levels between the 5th and 95th percentiles.
Integrative Array-Based Approach Identifies MZB1 as a Frequently Methylated Putative Tumor Suppressor in Hepatocellular Carcinoma
Authors: Satoshi Matsumura, Issei Imoto, Ken-ichi Kozaki, Takeshi Matsui, Tomoki Muramatsu, Mayuko Furuta, Shinji Tanaka, Michiie Sakamoto, Shigeki Arii, Johji Inazawa
Journal: Clinical Cancer Research (2012)

The aim of this study was the identification of novel tumor suppressor genes (TSG) silenced by DNA hypermethylation in hepatocellular carcinoma (HCC).We conducted integrative array-based approach for genome-wide screening of methylation targets using a methylated DNA immunoprecipitation-CpG island microarray and expression array in three universal hepatoma cell lines and normal liver tissue. Through detailed expression and functional analyses using hepatoma cell lines and primary HCC samples, we isolated novel TSGs for HCC.A total of 642 genes were identified as methylated in three hepatoma cell lines but unmethylated in normal liver tissue, whereas 204 genes on autosomes were identified as genes unexpressed but restored after treatment with 5-aza-2'-deoxycytidine in these cell lines and expressed in normal tissue. Through the integration of results of the two-array analyses and further validation analyses of expression and methylation status in 17 cell lines and 30 primary tumors of hepatoma, we identified MZB1, marginal zone B and B1 cell-specific protein, encoding an endoplasmic reticulum protein, as a putative TSG frequently methylated within its CpG island in hepatoma. Among 162 patients with primary HCC, silencing of MZB1 protein was significantly and independently associated with a worse outcome. Restoration of MZB1 expression in hepatoma cells reduced cell proliferation in vitro and in vivo through G(1)-arrest.These results suggest that methylation-mediated silencing of MZB1 expression leads to loss of its tumor-suppressive activity, which may be a factor in the hepatocarcinogenesis, and is a useful prognosticator in HCC.
Evaluation of Functionally Meaningful Measures for Clinical Trials of Cognition Enhancement in Schizophrenia
Authors: Michael F. Green, Nina R. Schooler, Robert S. Kern, Fred J. Frese, Wendy Granberry, Philip D. Harvey, Craig N. Karson, Nancy Peters, Michelle Stewart, Larry J. Seidman, John Sonnenberg, William S. Stone, David Walling, Ellen Stover, Stephen R. Marder
Journal: American Journal of Psychiatry (2011)

Objective: Because reduction of psychotic symptoms in schizophrenia does not result in adequate community functioning, efforts have shifted to other areas, such as cognitive impairment. The U.S. Food and Drug Administration requires that drugs for cognition enhancement in schizophrenia show improvement on two distinct outcome measures in clinical trials: an accepted cognitive performance battery and a functionally meaningful coprimary measure. The authors examined the reliability, validity, and practicality of functionally meaningful measures. Method: In this four-site validation study, schizophrenia patients were assessed at baseline (N=166) and 4 weeks later (N=144) on performance-based (Independent Living Scales, Test of Adaptive Behavior in Schizophrenia [TABS], and UCSD Performance-based Skills Assessment [UPSA]) and interview-based (Cognitive Assessment Interview and Clinical Global Impression Scale for Cognition) candidate coprimary measures. In addition, cognitive performance, community functioning, and clinical symptoms were assessed. Both full and short forms of the performance-based measures were evaluated. Results: All measures were well tolerated by patients, had adequate test-retest reliability, and showed good utility as a repeated measure. Measures differed in their correlation with cognitive performance, with performance-based measures having stronger correlations than interview-based measures. None of the measures had notable floor or ceiling effects or missing data. Conclusions: Among the full-form measures, the UPSA was judged to have the strongest overall properties. Among the short forms, the TABS and UPSA appeared to have the strongest features. Use of the short forms saves time, but at the cost of lower test-retest reliability and weaker correlations with cognitive performance.
Low-Dose Methotrexate: A Mainstay in the Treatment of Rheumatoid Arthritis
Authors: Bruce N. Cronstein
Journal: Pharmacological Reviews (2005)

Methotrexate administered weekly in low doses is a mainstay in the therapy of rheumatoid arthritis. Although originally developed as a folate antagonist for the treatment of cancer, its mechanism of action in the therapy of rheumatoid arthritis remains less clear. Several mechanisms have been proposed including inhibition of T cell proliferation via its effects on purine and pyrimidine metabolism, inhibition of transmethylation reactions required for the prevention of T cell cytotoxicity, interference with glutathione metabolism leading to alterations in recruitment of monocytes and other cells to the inflamed joint, and promotion of the release of the endogenous anti-inflammatory mediator adenosine. These mechanisms of action and the role of methotrexate in the suppression of rheumatoid arthritis are reviewed.
Improving the Quality of Decision-Making Processes for Prostate Cancer Screening: Progress and Challenges
Authors: Daniel S. Reuland, Michael Pignone
Journal: JAMA Internal Medicine (2013)

Guidelines recommend that patients be informed about potential benefits and harms from prostate cancer screening and that screening decisions involve a discussion between patients and their physicians.1,2Despite this consensus, achieving high-quality decision-making processes in practice is difficult.Clinicians function in a time-constrained environment and know that ordering a prostate-specific antigen (PSA) blood test is simple, whereas ensuring that patients fully understand the potential ramifications of entering a screening program is far more difficult and time-consuming.Explaining such concepts as biopsy threshold, falsepositive results, overdiagnosis, and uncertainty about magnitude of benefit is challenging and cannot be done quickly.
Inhibitory effect of somatostatin on gastric acid secretion and serum gastrin in dogs with and without duodenogastric reflux.
Authors: W E Thomas
Journal: Gut (1980)

The hypersecretion of gastric acid in response to pentagastrin, caused by duodenal reflux, was tested in dogs. An infusion of 0.25 micrograms/kg/h was found to restore the raised responses seen in the reflux dogs to control levels. Somatostatin was a strong inhibitor of pentagastrin-stimulated acid secretion and of gastrin release, but it was a weak inhibitor of histamine. These studies suggest that somatostatin may have played a part in acid homeostasis.
Matricellular Signaling Molecule CCN1 Attenuates Experimental Autoimmune Myocarditis by Acting as a Novel Immune Cell Migration Modulator
Authors: Madlen Rother, Stefanie Krohn, Gabriela Kania, Davy Vanhoutte, Andreas Eisenreich, Xiaomin Wang, Dirk Westermann, Kostas Savvatis, Nadine Dannemann, Carsten Skurk, Denise Hilfiker-Kleiner, Toni Cathomen, Henry Fechner, Ursula Rauch, Heinz-Peter Schultheiss, Stephane Heymans, Urs Eriksson, Carmen Scheibenbogen, Wolfgang Poller
Journal: Circulation (2010)

CCN1 is an evolutionary ancient matricellular protein that modulates biological processes associated with tissue repair. Induction at sites of injury was observed in conditions ranging from skin wounds to cardiac diseases, including ischemic and inflammatory cardiomyopathy. Here, we provide evidence of a novel function of CCN1 as a modulator of immune cell migration.to understand the role of CCN1 in cardiomyopathies and to evaluate its therapeutic potential, we overexpressed CCN1 using an adenoviral hepatotropic vector in murine experimental autoimmune myocarditis, a model of human inflammatory cardiomyopathy. CCN1 gene transfer significantly reduced cardiac disease score and immune cell infiltration. In vivo tracking of hemagglutinin epitope-tagged CCN1 revealed binding to spleen macrophages but not to cardiomyocytes. Unexpectedly, CCN1 therapy left cardiac chemokine and cytokine expression unchanged but instead strongly inhibited the migration of spleen macrophages and lymphocytes, as evidenced by ex vivo transwell assays. In accordance with the ex vivo data, in vitro preincubation with CCN1 diminished transwell migration of human monocytes and abrogated their chemotactic response to monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, and stromal cell-derived factor-1α. Further mechanistic studies showed that CCN1-driven modulation of immune cell migration is mimicked in part by cyclic RGD peptides currently in clinical evaluation for cancer therapy.our proof-of-concept study suggests investigation of CCN1 as a novel, endogenous "parent compound" for chemotaxis modulation and of cyclic RGD peptides as a class of partially CCN1-mimetic drugs with immediate potential for clinical evaluation in cardiac diseases associated with chronic pathogenic inflammation.
Recurrence of Urothelial Carcinoma of the Bladder: A Role for Insulin-Like Growth Factor-II Loss of Imprinting and Cytoplasmic E-Cadherin Immunolocalization
Authors: Emma M. Gallagher, Deirdre M. O'Shea, Patricia Fitzpatrick, Michèle Harrison, Breege Gilmartin, Jenny A. Watson, Trevor Clarke, Martin O. Leonard, Aloysius McGoldrick, Maria Meehan, Chanel Watson, Fiona Furlong, Patrick O'Kelly, John M. Fitzpatrick, Peter A. Dervan, Anthony O'Grady, Elaine W. Kay, Amanda McCann
Journal: Clinical Cancer Research (2008)

Abstract Purpose: This study documents the frequency of insulin-like growth factor-II (IGF-II) loss of imprinting (LOI) in a series of 87 bladder tissues. E-cadherin (CDH1) immunolocalization was also investigated due to the known redistribution of this adherence protein to the cytoplasm following exogenous exposure to IGF-II. Experimental Design: Informative IGF-II cases were identified following DNA-PCR amplification and subsequent sequencing of the transcribable ApaI RFLP in exon 9 of IGF-II. Similar approaches using primer-specific cDNA templates identified the imprinting status of IGF-II in these informative cases. CDH1 cellular localization was assessed on a tissue microarray platform of 114 urothelial carcinoma of the bladder (UCB) cases (70 pTa noninvasive and 44 pT1 lamina propria invasive) using the commercially available Novocastra antibody. Results: IGF-II LOI was evident in 7 of 17 (41%) UCB tumors and 4 of 11 (36%) tumor-associated normal urothelial samples. Two of four pT1 grade 3 tumors, the subject of much debate concerning their suitability for radical cystectomy, showed LOI at the IGF-II locus. In those tumors showing IGF-II LOI, 4 of 7 (57%) displayed concomitant CDH1 cytoplasmic staining. In contrast, only 3 of 10 (30%) IGF-II maintenance of imprinting tumors had concomitant CDH1 cytoplasmic localization. UCB cell lines displaying cytoplasmic CDH1 immunolocalization expressed significantly higher levels of IGF-II (CAL29, HT1376, and RT112) compared with RT4, a cell line displaying crisp membranous CDH1 staining. Finally, cytoplasmic CDH1 staining was an independent predictor of a shorter time to recurrence independent of tumor grade and stage. Conclusions: We suggest that CDH1 cytoplasmic immunolocalization as a result of increased IGF-II levels identifies those nonmuscle invasive presentations most likely to recur and therefore might benefit from more radical nonconserving bladder surgery.
Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2
Authors: M. Piccart, G.N. Hortobagyi, M. Campone, K.I. Pritchard, F. Lebrun, Y. Ito, S. Noguchi, A. Perez, H.S. Rugo, I. Deleu, H.A. Burris, L. Provencher, P. Neven, M. Gnant, M. Shtivelband, C. Wu, J. Fan, W. Feng, T. Taran, J. Baselga
Journal: Annals of Oncology (2014)
Barcelona Clinic Liver Cancer staging and transplant survival benefit for patients with hepatocellular carcinoma: a multicentre, cohort study
Authors: Alessandro Vitale, Rafael Ramirez Morales, Giacomo Zanus, Fabio Farinati, Patrizia Burra, Paolo Angeli, Anna Chiara Frigo, Paolo Del Poggio, Gianludovico Rapaccini, Maria Anna Di Nolfo, Luisa Benvegnù, Marco Zoli, Franco Borzio, Edoardo Giovanni Giannini, Eugenio Caturelli, Maria Chiaramonte, Franco Trevisani, Umberto Cillo
Journal: The Lancet Oncology (2011)
Dynamic Calcium Movement Inside Cardiac Sarcoplasmic Reticulum During Release
Authors: Eckard Picht, Aleksey V. Zima, Thomas R. Shannon, Alexis M. Duncan, Lothar A. Blatter, Donald M. Bers
Journal: Circulation Research (2011)

Intra-sarcoplasmic reticulum (SR) free [Ca] ([Ca](SR)) provides the driving force for SR Ca release and is a key regulator of SR Ca release channel gating during normal SR Ca release or arrhythmogenic spontaneous Ca release events. However, little is known about [Ca](SR) spatiotemporal dynamics.To directly measure local [Ca](SR) with subsarcomeric spatiotemporal resolution during both normal global SR Ca release and spontaneous Ca sparks and to evaluate the quantitative implications of spatial [Ca](SR) gradients.Intact and permeabilized rabbit ventricular myocytes were subjected to direct simultaneous measurement of cytosolic [Ca] and [Ca](SR) and FRAP (fluorescence recovery after photobleach). We found no detectable [Ca](SR) gradients between SR release sites (junctional SR) and Ca uptake sites (free SR) during normal global Ca release, clear spatiotemporal [Ca](SR) gradients during isolated Ca blinks, faster intra-SR diffusion in the longitudinal versus transverse direction, 3- to 4-fold slower diffusion of fluorophores in the SR than in cytosol, and that intra-SR Ca diffusion varies locally, dependent on local SR connectivity. A computational model clarified why spatiotemporal gradients are more detectable in isolated local releases versus global releases and provides a quantitative framework for understanding intra-SR Ca diffusion.Intra-SR Ca diffusion is rapid, limiting spatial [Ca](SR) gradients during excitation-contraction coupling. Spatiotemporal [Ca](SR) gradients are apparent during Ca sparks, and these observations constrain models of dynamic Ca movement inside the SR. This has important implications for myocyte SR Ca handling, synchrony, and potentially arrhythmogenic spontaneous contraction.