tbuckley/cabot-search huggingface dataset:
Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand (TRAIL) Sequentially Upregulates Nitric Oxide and Prostanoid Production in Primary Human Endothelial Cells
Authors: Giorgio Zauli, Assunta Pandolfi, Arianna Gonelli, Roberta Di Pietro, Simone Guarnieri, Giovanni Ciabattoni, Rosalba Rana, Marco Vitale, Paola Secchiero
Journal: Circulation Research (2003)

Endothelial cells express tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) receptors, but the function of TRAIL in endothelial cells is not completely understood. We explored the role of TRAIL in regulation of key intracellular signal pathways in endothelial cells. The addition of TRAIL to primary human endothelial cells increased phosphorylation of endothelial nitric oxide synthase (eNOS), NOS activity, and NO synthesis. Moreover, TRAIL induced cell migration and cytoskeleton reorganization in an NO-dependent manner. TRAIL did not activate the NF-κB or COX-2 pathways in endothelial cells. Instead, TRAIL increased prostanoid production (PGE 2 =PGI 2 &gt;TXA 2 ), which was preferentially inhibited by the COX-1 inhibitor SC-560. Because NO and prostanoids play a crucial role in the state of blood vessel vasodilatation and angiogenesis, our data suggest that TRAIL might play an important role in endothelial cell function.
The Association between Acute Respiratory Distress Syndrome, Delirium, and In-Hospital Mortality in Intensive Care Unit Patients
Authors: S. Jean Hsieh, Graciela J. Soto, Aluko A. Hope, Ana Ponea, Michelle N. Gong
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Both acute respiratory distress syndrome (ARDS) and intensive care unit (ICU) delirium are associated with significant morbidity and mortality. However, the risk of delirium and its impact on mortality in ARDS patients is unknown.To determine if ARDS is associated with a higher risk for delirium compared with respiratory failure without ARDS, and to determine the association between ARDS and in-hospital mortality after adjusting for delirium.Prospective observational cohort study of adult ICU patients admitted to two urban academic hospitals.Delirium was assessed daily using the Confusion Assessment Method for the ICU and Richmond Agitation and Sedation Scale. Of the 564 patients in our cohort, 48 had ARDS (9%). Intubated patients with ARDS had the highest prevalence of delirium compared with intubated patients without ARDS and nonintubated patients (73% vs. 52% vs. 21%, respectively; P < 0.001). After adjusting for common risk factors for delirium, ARDS was associated with a higher risk for delirium compared with mechanical ventilation without ARDS (odds ratio [OR], 6.55 [1.56-27.54]; P = 0.01 vs. OR, 1.98 [1.16-3.40]; P < 0.013); reference was nonintubated patients. Although ARDS was significantly associated with hospital mortality (OR, 10.44 [3.16-34.50]), the effect was largely reduced after adjusting for delirium and persistent coma (OR, 5.63 [1.55-20.45]).Our findings suggest that ARDS is associated with a greater risk for ICU delirium than mechanical ventilation alone, and that the association between ARDS and in-hospital mortality is weakened after adjusting for delirium and coma. Future studies are needed to determine if prevention and reduction of delirium in ARDS patients can improve outcomes.
Humoral and Cell-mediated Autoimmune Reactions to Human Acidic Ribosomal P2 Protein in Individuals Sensitized to <i>Aspergillus fumigatus</i> P2 Protein
Authors: Christina Mayer, Ulrich Appenzeller, Heike Seelbach, Gernot Achatz, Hannes Oberkofler, Michael Breitenbach, Kurt Blaser, Reto Crameri
Journal: The Journal of Experimental Medicine (1999)

A panel of cDNAs encoding allergenic proteins was isolated from an Aspergillus fumigatus cDNA library displayed on the surface of filamentous phage. Solid phase–immobilized serum immunoglobulin E (IgE) from A. fumigatus–allergic individuals was used to enrich phage displaying IgE-binding molecules. One of the cDNAs encoded a 11.1-kD protein that was identified as acidic ribosomal phosphoprotein type 2 (P2 protein). The allergen, formally termed rAsp f 8, shares &amp;gt;62% sequence identity and &amp;gt;84% sequence homology to corresponding eukaryotic P2 proteins, including human P2 protein. The sequences encoding human and fungal P2 protein were subcloned, expressed in Escherichia coli as His6-tagged fusion proteins, and purified by Ni2+–chelate affinity chromatography. Both recombinant P2 proteins were recognized by IgE antibodies from allergic individuals sensitized to the A. fumigatus P2 protein and elicited strong type 1–specific skin reactions in these individuals. Moreover, human and fungal P2 proteins induced proliferative responses in peripheral blood mononuclear cells of A. fumigatus– allergic subjects sensitized to the fungal P2 protein. These data provide strong evidence for in vitro and in vivo humoral and cell-mediated autoreactivity to human P2 protein in patients suffering from chronic A. fumigatus allergy.
Percutaneous drainage of echinococcal cysts (PAIR---puncture, aspiration, injection, reaspiration): results of a worldwide survey for assessment of its safety and efficacy Reply
Authors: C FILICE
Journal: Gut (2000)

Editor,—In 1996 a letter ( Gut 1996; 38 :936) about the use of PAIR ( p uncture, a spiration, i njection of a scolecidal agent, r easpiration) raised a criticism of Dr Morris, a leading expert on the treatment of echinococcosis.1 At the same time the WHO Informal Working Group on Echinococcosis launched a survey to evaluate the status of this procedure. A number of centres around the world known to be active in this field were requested to complete forms for patients treated with PAIR: 765 abdominal cysts, mostly hepatic, treated with this technique were reported from various countries. We report the results of this survey (table 1). View this table: Table 1 Results of the survey on PAIR by the WHO Informal Working Group on Echinococcosis Either needles (18–22 gauge) or catheters (5–9 French gauge), depending on the size and location of the cysts, were used. Scolecidal agents were mainly 20% hypertonic saline and 95% ethanol solution. After aspiration and parasitological control of the fluid, a quantity of scolecidal agent, approximately equivalent to one third of the amount aspirated, was injected into the cysts and left for a time varying from 5 to 30 minutes, and then reaspirated: only in the cases … Professor D Morris. Email: David.Morris{at}unsw.edu.au
Phase II Trial of Capecitabine and Weekly Paclitaxel As First-Line Therapy for Metastatic Breast Cancer
Authors: Joanne L. Blum, E. Claire Dees, Aparna Chacko, Lisa Doane, Sukumar Ethirajan, Judith Hopkins, Richard McMahon, Suzan Merten, Angel Negron, Marcus Neubauer, Des Ilegbodu, Kristi A. Boehm, Lina Asmar, Joyce A. O'Shaughnessy
Journal: Journal of Clinical Oncology (2006)

The taxanes and capecitabine have synergistic antitumor activity in preclinical models. This trial was designed to determine the efficacy and tolerability of weekly paclitaxel plus capecitabine as first-line treatment for metastatic breast cancer (MBC).Participants had histologically proven breast cancer, with measurable metastatic disease by Response Evaluation Criteria in Solid Tumors Group. Exclusion criteria included prior taxane therapy or any prior capecitabine or infusional fluorouracil. Participants received capecitabine 825 mg/m2/dose orally bid (1,650 mg/m2/d) for days 1 to 14. Paclitaxel 80 mg/m2 was administered intravenously weekly on days 1 and 8. Cycles were repeated every 3 weeks. Responders (complete or partial) or those with stable disease were treated until progression of disease or intolerable toxicity.Fifty-five women were enrolled; 94% received study therapy as first-line treatment for MBC. In the intent-to-treat population, objective responses (partial) were achieved in 30 patients (55%; 95% CI, 40% to 69%), and six additional patients had stable disease for 6 months or longer (clinical benefit rate of 65%). The median duration of response was 10 months (range, 2.5 to 18.7 months). Dose modifications and reductions were common, particularly for capecitabine, leading to a delivered dose-intensity of 75% for capecitabine and 91% for paclitaxel. The most frequent grade 3 to 4 treatment-related adverse events were hand-foot skin reaction (n = 10); neutropenia (n = 7); fatigue (n = 4); and leukopenia, diarrhea, and pain (n = 3 each).Capecitabine in combination with weekly paclitaxel is an active and tolerable regimen as first-line therapy for women with MBC.
High level of functional dickkopf-1 predicts protection from syndesmophyte formation in patients with ankylosing spondylitis
Authors: Gisela Ruiz Heiland, Heiner Appel, Denis Poddubnyy, Jochen Zwerina, Axel Hueber, Hildrun Haibel, Xenofon Baraliakos, Joachim Listing, Martin Rudwaleit, Georg Schett, Joachim Sieper
Journal: Annals of the Rheumatic Diseases (2011)

The molecular mechanisms of syndesmophyte formation in ankylosing spondylitis (AS) are yet to be characterised. Molecules involved in bone formation such as Wnt proteins and their antagonists probably drive syndesmophyte formation in AS.This study investigated sequential serum levels of functional dickkopf-1 (Dkk1), a potent Wnt antagonist involved in bone formation in arthritis, by capture ELISA with its receptor LRP6 in 65 AS patients from the German Spondyloarthritis Inception Cohort. Dkk1 levels were then related to structural progression (syndesmophyte formation) as well as sclerostin and C-reactive protein (CRP) levels.Functional Dkk1 levels were significantly (p=0.025) higher in patients with no syndesmophyte growth (6.78 ± 5.48 pg/ml) compared with those with syndesmophyte growth (4.13 ± 2.10 pg/ml). Dkk1 levels were highly correlated to serum sclerostin levels (r=0.71, 95% CI 0.53 to 0.82; p<0.001) but not to CRP (r=0.15, 95% CI -0.10 to 0.38; p=0.23).AS patients with no syndesmophyte formation show significantly higher functional Dkk1 levels suggesting that blunted Wnt signalling suppresses new bone formation and consequently syndesmophyte growth and spinal ankylosis. Similar to serum sclerostin levels, the functional Dkk1 level thus emerges as a potential biomarker for structural progression in patients with AS.
Personalizing, not patronizing: the case for patient autonomy by unbiased presentation of management options in stage I testicular cancer
Authors: J. Oldenburg, J. Aparicio, J. Beyer, G. Cohn-Cedermark, M. Cullen, T. Gilligan, U. De Giorgi, M. De Santis, R. de Wit, S.D. Fosså, J.R. Germà-Lluch, S. Gillessen, H.S. Haugnes, F. Honecker, A. Horwich, A. Lorch, D. Ondruš, G. Rosti, A.J. Stephenson, T. Tandstad
Journal: Annals of Oncology (2014)
PI-103, a dual inhibitor of Class IA phosphatidylinositide 3-kinase and mTOR, has antileukemic activity in AML
Authors: S Park, N Chapuis, V Bardet, J Tamburini, N Gallay, L Willems, Z A Knight, K M Shokat, N Azar, F Viguié, N Ifrah, F Dreyfus, P Mayeux, C Lacombe, D Bouscary
Journal: Leukemia (2008)
Central cyanosis on a psychiatric unit treated at the Salford Royal Hospital: Table 1
Authors: Darren Green, Peter Barry, Heather D Green
Journal: Thorax (2014)

We describe a case of acquired methaemoglobinaemia due to frequent use of the ‘legal high’ known as ‘Pink Panthers’. This contains 5,6-Methylenedioxy-2-aminoindane and 2-Aminoindane, both amphetamine analogues with the potential to cause methaemoglobinaemia. Furthermore, the most common ‘cutting agent’ for legal highs in the UK is benzocaine, also known to cause methaemoglobinaemia. Given the increasing prevalence of legal highs, particularly those containing added benzocaine, such presentations may become more common. Furthermore, in one case series, benzocaine gel used for toothache was the second most common reason for hospitalisation due to acquired methaemoglobinaemia after dapsone use. Indeed, the Federal Drug Agency has issued as public warning as to the risk of these products. We therefore think that clinicians and the public should be made more aware of the risk associated with such agents.
Variants on 9p24 and 8q24 Are Associated with Risk of Colorectal Cancer: Results from the Colon Cancer Family Registry
Authors: Jenny N. Poynter, Jane C. Figueiredo, David V. Conti, Kathleen Kennedy, Steven Gallinger, Kimberly D. Siegmund, Graham Casey, Stephen N. Thibodeau, Mark A. Jenkins, John L. Hopper, Graham B. Byrnes, John A. Baron, Ellen L. Goode, Maarit Tiirikainen, Noralane Lindor, John Grove, Polly Newcomb, Jeremy Jass, Joanne Young, John D. Potter, Robert W. Haile, David J. Duggan, Loic Le Marchand
Journal: Cancer Research (2007)

Recent publications have reported that common variants on 8q24 are associated with both prostate and colorectal cancers (CRC). In addition, one of these studies (the ARCTIC study) initially observed an association with a single nucleotide polymorphism (SNP) on 9p24 that was not confirmed in some of their validation data sets. In the research described here, we conducted a case-unaffected sibling analysis using population- and clinic-based discordant sibships (N = 1,567 sibships) from the Colon Cancer Family Registry (Colon CFR) to investigate the associations between common variants at 9p24 and 8q24 and risk of CRC. We also evaluated whether these associations differed by age, family history, and tumor characteristics, including microsatellite instability and tumor site. Associations were estimated using conditional logistic regression, treating sibship as the matching factor. Analyses were adjusted for age and sex, and stratified by ascertainment source (population versus clinic). We observed an association between a SNP on 9p24 (rs719725) and risk of CRC in the population-based series (AA versus CC: odds ratios, 1.46; 95% confidence interval, 1.06-2.02; AC versus CC: odds ratios, 1.50; 95% confidence interval, 1.14-1.98; P = 0.011 on 2 df). In the population-based series, we also detected statistically significant associations between two SNPs on 8q24, rs10505477 and rs6983267, and risk of CRC (P = 0.005 and P = 0.002, respectively). There was no evidence of statistically significant heterogeneity by age at diagnosis, family history of CRC, microsatellite instability, or tumor site at either locus and no evidence of interaction between SNPs on 8q24 and 9p24. These data suggest that common variants may play important roles in the risk of CRC.
British Thoracic Society study of cryptogenic fibrosing alveolitis: current presentation and initial management. Fibrosing Alveolitis Subcommittee of the Research Committee of the British Thoracic Society
Authors: I. D. Johnston, R. J. Prescott, J. C. Chalmers, R. M. Rudd
Journal: Thorax (1997)

BACKGROUND: Mortality due to cryptogenic fibrosing alveolitis (CFA) is increasing, particularly in the elderly. Optimum management remains uncertain and previous studies of the disease have largely been from specialist centres. A national study was carried out of the presentation and initial management of CFA in the UK. METHODS: All respiratory physicians in England, Scotland and Wales were invited to enter patients with newly diagnosed CFA over a two year period. CFA was diagnosed on histological grounds or according to clinical criteria which included the absence of a defined connective tissue disorder or pneumoconiosis. Participating physicians (n = 150) completed a questionnaire at patient entry and at all subsequent follow up visits and death. RESULTS: A total of 588 patients (373 men, 63%) were studied of whom 441 (75%) were referrals from primary care. Their mean (SD) age was 67.4 (10.0) years and median duration of symptoms at presentation was 9.0 months. Clubbing was more common in men (203/373; 54%) than in women (86/ 215; 40%); 209 patients (36%) were graded as severely breathless at presentation. A history of dust exposure (organic or inorganic) was present in 274 patients (47%) of whom 87 had had some exposure to asbestos. Subjects exposed to dust were more likely to have smoked and had slightly higher mean lung volumes, but were otherwise indistinguishable from those not exposed in terms of clinical presentation, management, and outcome. Transbronchial biopsy specimens were taken in 164 patients (28%) and open lung biopsy specimens in 73 (12%), but 60% had no histological diagnostic procedure. Biopsy procedures were more likely to be performed in younger patients, those with better lung function, and those with a history of asbestos exposure. At presentation a decision not to initiate specific treatment was made in 284 cases (48%). The decision to initiate treatment was made predominantly on symptomatic grounds. Two years after the close of entry to the study 266 patients (45%) had died. CONCLUSIONS: CFA is predominantly a disease of elderly patients and has a poor prognosis. Physicians generally considered CFA to be a clinical diagnosis and did not initiate treatment in up to half of patients at presentation.
Reporting of long-term extension studies: lack of consistency calls for consensus
Authors: Maya H Buch, Daniel Aletaha, Paul Emery, Josef S Smolen
Journal: Annals of the Rheumatic Diseases (2011)

Double-blind, randomised controlled studies represent the gold-standard approach to determine the safety and efficacy of therapeutic interventions. In chronic conditions such as rheumatoid arthritis (RA), long-term data are vital to confirm maintenance of effect and identify potential safety signals. The recent introduction of numerous biological therapies for RA has been followed by various long-term extension (LTE) studies. Although useful, the design and method of analysis in such studies vary significantly, partly due to their complexity. This viewpoint highlights general considerations needed when undertaking a LTE study and illustrates the lack of consistency in studies of RA to date. It addresses issues of selection bias, patient discontinuation and missing data. Although used for safety reporting, the lack of adequate powering makes LTE studies of limited benefit. Ethical considerations and challenges are highlighted, including potential conflicts of interest. Finally, the authors suggest the need for consensus to ensure more reliable interpretation and application of data for clinical practice. Following the development of guidelines on reporting of clinical trials in RA and more recently, registry data, a similar approach for LTE studies would be a useful endeavour.
Phase III Randomized Trial of Amifostine as a Radioprotector in Head and Neck Cancer
Authors: David M. Brizel, Todd H. Wasserman, Michael Henke, Vratislav Strnad, Volkar Rudat, Alain Monnier, Francois Eschwege, Jay Zhang, Lesley Russell, Wolfgang Oster, Rolf Sauer
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Radiotherapy for head and neck cancer causes acute and chronic xerostomia and acute mucositis. Amifositine and its active metabolite, WR-1065, accumulate with high concentrations in the salivary glands. This randomized trial evaluated whether amifostine could ameliorate these side effects without compromising the effectiveness of radiotherapy in these patients. PATIENTS AND METHODS: Patients with previously untreated head and neck squamous cell carcinoma were eligible. Primary end points included the incidence of grade ≥ 2 acute xerostomia, grade ≥ 3 acute mucositis, and grade ≥ 2 late xerostomia and were based on the worst toxicity reported. Amifostine was administered (200 mg/m 2 intravenous) daily 15 to 30 minutes before irradiation. Radiotherapy was given once daily (1.8 to 2.0 Gy) to doses of 50 to 70 Gy. Whole saliva production was quantitated preradiotherapy and regularly during follow-up. Patients evaluated their symptoms through a questionnaire during and after treatment. Local-regional control was the primary antitumor efficacy end point. RESULTS: Nausea, vomiting, hypotension, and allergic reactions were the most common side effects. Fifty-three percent of the patients receiving amifostine had at least one episode of nausea and/or vomiting, but it only occurred with 233 (5%) of 4,314 doses. Amifostine reduced grade ≥ 2 acute xerostomia from 78% to 51% (P &lt; .0001) and chronic xerostomia grade ≥ 2 from 57% to 34% (P = .002). Median saliva production was greater with amifostine (0.26 g v 0.10 g, P = .04). Amifostine did not reduce mucositis. With and without amifostine, 2-year local-regional control, disease-free survival, and overall survival were 58% versus 63%, 53% versus 57%, and 71% versus 66%, respectively. CONCLUSION: Amifostine reduced acute and chronic xerostomia. Antitumor treatment efficacy was preserved.
Pseudocapillarization and associated energy limitation in the aged rat liver
Authors: D Le Couteur
Journal: Hepatology (2001)

Age-related impairment of drug metabolism by the liver is consistent with hepatocyte hypoxia, suggestive of the development of a diffusional barrier to oxygen supply. Because the effects of aging on the diffusional pathway (sinusoidal endothelium and space of Disse) have not been described, we performed comparative studies on the livers of Fischer F344 rats aged 4 to 7, 12 to 15, and 24 to 27 months. Light-microscopic examination revealed no evidence of fibrosis, cirrhosis, or other specific pathology. In contrast, scanning and transmission electron-microscopic examination revealed that aging is associated with pseudocapillarization of the sinusoidal endothelium, indicated by defenestration with reduced porosity, thickening of the endothelium, infrequent development of basal lamina, and only minor collagen deposits in the space of Disse. Furthermore, immunohistochemistry studies showed strong expression of collagen IV, moderate expression of factor VIII-related antigen, and weak expression of collagen I along the sinusoids of livers from old rats (P < .0001). In vitro 31P magnetic resonance spectroscopy analysis showed that aging is associated with changes in high-energy phosphate and other metabolites, consistent with hepatocyte hypoxia. Aging in the liver is associated with changes in the sinusoidal endothelium and space of Disse that may restrict the availability of oxygen and other substrates.
Selective probiotic bacteria induce IL-10–producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell–specific intercellular adhesion molecule 3–grabbing nonintegrin
Authors: Hermelijn H. Smits, Anneke Engering, Desiree van der Kleij, Esther C. de Jong, Kim Schipper, Toni M.M. van Capel, Bas A.J. Zaat, Maria Yazdanbakhsh, Eddy A. Wierenga, Yvette van Kooyk
Journal: Journal of Allergy and Clinical Immunology (2005)