tbuckley/cabot-search huggingface dataset:
Survival End Point Reporting in Randomized Cancer Clinical Trials: A Review of Major Journals
Authors: Simone Mathoulin-Pelissier, Sophie Gourgou-Bourgade, Franck Bonnetain, Andrew Kramar
Journal: Journal of Clinical Oncology (2008)

Several publications showed that the standards for reporting randomized clinical trials (RCTs) might not be entirely suitable. Our aim was to evaluate the reporting of survival end points in cancer RCTs.A search in MEDLINE databases identified 274 cancer RCTs published in 2004 in four general medical journals and four clinical oncology journals. Eligible articles were those that reported primary analyses of RCT with survival end points. Methodologists reviewed and scored the articles according to seven key points: prevalence of complete definition of survival end points (time of origin, survival events, censoring events) and relevant information about their analyses (estimation or effect size, precision, number of events, patients at risk). Concordance of key points was evaluated from a random subsample.After screening, 125 articles were selected; 104 trials were phase III (83%) and 98 publications (78%) were obtained from oncology journals. Among these RCTs, a total of 267 survival end points were recorded, and overall survival (OS) was the most frequent outcome (118 terms, 44%). Survival terms were totally defined for 113 end points (42%) in 65 articles (52%). Accurate information about analysis was retrieved for 73 end points (27%) in 40 articles (32%). The less well-defined information was the number of patients at risk (55%). The reliability was good (kappa = 0.72). Finally, according to the key points, optimal reporting was found in 33 end points (12%) or 10 publications.A majority of articles failed to provide a complete reporting of survival end points, thus adding another source of uncontrolled variability.
Cytokine expression in normal, atopic, and asthmatic subjects using the combination of sputum induction and the polymerase chain reaction.
Authors: C M Gelder, P S Thomas, D H Yates, I M Adcock, J F Morrison, P J Barnes
Journal: Thorax (1995)

BACKGROUND--The importance of cytokines in the asthmatic inflammatory response is becoming apparent. The aim of this study was to determine whether the non-invasive method of induced sputum combined with the polymerase chain reaction would allow the detection of messenger RNA (mRNA) encoding a range of cytokines on a qualitative basis. METHODS--Four groups were studied comprising 10 normal subjects, six atopic, 10 mild and five moderately severe asthmatic subjects. Sputum was induced by the inhalation of nebulised 3.5% saline and total RNA extracted from the expectorated cells. Expression of cytokine message within induced sputum was examined by reverse transcription and the polymerase chain reaction (PCR) using primers specific for a range of cytokines (IL-1 alpha, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, RANTES, TNF alpha, IFN alpha, IFN gamma). Presence or absence of the signal was determined at 35 and 70 cycles of PCR by electrophoretic size fractionation on ethidium bromide stained agarose gels. RESULTS--Cytokine message was detectable in sputum by this method. All samples showed a positive result for actin control. Analysis of signal for the cytokines in all subjects showed that, at 70 cycles, IL-1, IL-5, IL-8, and TNF alpha were detected in more subjects than would be expected by chance. IL-5 mRNA was detected in more of the asthmatic patients (moderate 80%, mild 40%) than in the atopic subjects (33%), who in turn showed expression of this cytokine in more individuals than nonatopic subjects (10%). CONCLUSIONS--The combination of sputum induction and PCR appears to be a useful, non-invasive tool to explore the chronic inflammation of asthma and possibly other lung disorders. It should enable differences between normal and asthmatic subjects to be identified for future confirmation by quantitative techniques.
RELATIONSHIP BETWEEN NONSUSTAINED VENTRICULAR TACHYCARDIA AND VASCULAR DEATH IN PATIENTS WITH ACUTE CORONARY SYNDROME IN THE PLATO (PLATELET INHIBITION AND PATIENT OUTCOMES) TRIAL
Authors: An Hong Bui, Christopher Cannon, Philippe Steg, Robert Storey, Steen Husted, Fang Ren, Stefan James, Eric Michelson, Jay Horrow, Lars Wallentin, Benjamin Scirica
Journal: Journal of the American College of Cardiology (2012)
HETEROGENEITY OF THE CELLULAR IMMUNE RESPONSE
Authors: Robert C. Bast, Eleanor J. Manseau, Harold F. Dvorak
Journal: The Journal of Experimental Medicine (1971)

Lymph node cells from guinea pigs immunized with HSA in complete Freund's adjuvant were grown in cultures containing different concentrations of specific antigen. Stimulation of thymidine incorporation was induced with progressively lower concentrations of HSA at successive intervals after sensitization. Moreover, the intensity of delayed skin reactions and the magnitude of stimulation in vitro increased over the same interval. These events are considered compatible with an evolution of the cellular immune response resulting from the selection of lymphoid cells by decreasing concentrations of antigen in vivo. Cells from animals rendered tolerant to HSA failed to respond to specific antigen in culture. As tolerance waned, stimulation was achieved at high but not low antigen concentrations. Tolerance, measured by cutaneous reactivity or by lymphocyte stimulation, was less readily induced in animals sensitized with adjuvant containing a reduced concentration of mycobacteria. Lymph nodes from these animals contained a large population of cells reactive at high antigen concentration, presumably less susceptible to the toleragenic effect of intravenous antigen. The dissociation of delayed hypersensitivity and antibody formation observed early in the immune response and upon recovery from tolerance has permitted correlation of lymphocyte stimulation with delayed hypersensitivity and cutaneous basophil hypersensitivity respectively.
Increased arginase activity contributes to airway remodelling in chronic allergic asthma
Authors: H. Maarsingh, B.G.J. Dekkers, A.B. Zuidhof, I.S.T. Bos, M.H. Menzen, T. Klein, G. Flik, J. Zaagsma, H. Meurs
Journal: European Respiratory Journal (2011)

Airway remodelling, characterised by increased airway smooth muscle (ASM) mass, subepithelial fibrosis, goblet cell hyperplasia and mucus gland hypertrophy, is a feature of chronic asthma. Increased arginase activity could contribute to these features via increased formation of polyamines and l -proline downstream of the arginase product l -ornithine, and via reduced nitric oxide synthesis. Using the specific arginase inhitibor 2(S)-amino-6-boronohexanoic acid (ABH), we studied the role of arginase in airway remodelling using a guinea pig model of chronic asthma. Ovalbumin-sensitised guinea pigs were treated with ABH or PBS via inhalation before each of 12 weekly allergen or saline challenges, and indices of arginase activity, and airway remodelling, inflammation and responsiveness were studied 24 h after the final challenge. Pulmonary arginase activity of repeatedly allergen-challenged guinea pigs was increased. Allergen challenge also increased ASM mass and maximal contraction of denuded tracheal rings, which were prevented by ABH. ABH also attenuated allergen-induced pulmonary hydroxyproline (fibrosis) and putrescine, mucus gland hypertrophy, goblet cell hyperplasia, airway eosinophilia and interleukin-13, whereas an increased l -ornithine/ l -citrulline ratio in the lung was normalised. Moreover, allergen-induced hyperresponsiveness of perfused tracheae was fully abrogated by ABH. These findings demonstrate that arginase is prominently involved in allergen-induced airway remodelling, inflammation and hyperresponsiveness in chronic asthma.
Circulating Soluble Transferrin Receptor According to Glucose Tolerance Status and Insulin Sensitivity
Authors: José Manuel Fernández-Real, José Maria Moreno, Abel López-Bermejo, Berta Chico, Joan Vendrell, Wifredo Ricart
Journal: Diabetes Care (2007)

The relationships between iron metabolism and type 2 diabetes are bidirectional: iron affects glucose metabolism and glucose metabolism impinges on several iron metabolic pathways. The mechanisms of these interactions depend on poorly known factors. We aimed to study the contribution of the serum soluble transferrin receptor (sTfR).Circulating sTfR was evaluated in 221 men (97 with normal glucose tolerance [NGT], 36 with impaired glucose tolerance, and 88 with type 2 diabetes). In a subset of these subjects, glucose tolerance (oral glucose tolerance test [OGTT]), minimal model-derived insulin sensitivity, and sTfR during the OGTT were also evaluated.Men with altered glucose tolerance showed significantly increased sTfR (9.4 +/- 4.4 vs. 8.2 +/- 2.6 microg/ml, P = 0.02) and higher serum ferritin than men with NGT. Serum sTfR was negatively associated with serum ferritin (r = -0.16, P = 0.02). sTfR correlated with several clinical and metabolic variables such as systolic blood pressure, glycated hemoglobin, and glucose and insulin values during OGTT. Insulin sensitivity was also negatively associated with sTfR in NGT and nonobese subjects. BMI (P = 0.01), serum ferritin (P = 0.025), and insulin sensitivity (P < 0.0001) contributed independently to 21% of sTfR variance. Serum sTfR concentration did not significantly change during the OGTT.Both insulin sensitivity and glucose tolerance status are significantly associated with serum sTfR concentrations, although insulin sensitivity predicts independently circulating sTfR, mainly in subjects with NGT. The implications of the interrelationships between iron and glucose metabolism should be investigated further.
Treatment of saphenous vein graft lesions with drug-eluting stents
Authors: Lei Ge, Ioannis Iakovou, Giuseppe M. Sangiorgi, Alaide Chieffo, Gloria Melzi, John Cosgrave, Matteo Montorfano, Iassen Michev, Flavio Airoldi, Mauro Carlino, Nicola Corvaja, Antonio Colombo
Journal: Journal of the American College of Cardiology (2005)
Phase I, Pharmacokinetic, and Biological Study of Erlotinib in Combination with Paclitaxel and Carboplatin in Patients with Advanced Solid Tumors
Authors: Amita Patnaik, Debra Wood, Anthony W. Tolcher, Marta Hamilton, Jeffrey I. Kreisberg, Lisa A. Hammond, Garry Schwartz, Muralidhar Beeram, Manuel Hidalgo, Monica M. Mita, Julie Wolf, Paul Nadler, Eric K. Rowinsky
Journal: Clinical Cancer Research (2006)

To assess the feasibility of administering erlotinib, an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, in combination with paclitaxel and carboplatin, and to identify pharmacokinetic interactions, evaluate downstream effects of EGFR inhibition on surrogate tissues, and seek preliminary evidence for clinical activity.Patients with advanced solid malignancies were treated continuously with erlotinib at doses of 100, 125, and 150 mg/d orally along with fixed i.v. doses of paclitaxel 225 mg/m(2) and carboplatin AUC 6 mg x min/mL, both on day 1 every 3 weeks.Twenty evaluable patients were treated with 136 courses of erlotinib, paclitaxel, and carboplatin. Myelosuppression, skin rash, and diarrhea were the principal toxicities. Dose limiting diarrhea occurred in 1 of 6 patients at the 100 mg erlotinib dose level, whereas 0 of 9 evaluable patients at the 125 mg erlotinib dose level experienced dose limiting toxicity and 3 of 5 evaluable patients at 150 mg erlotinib experienced dose limiting skin rash and neutropenic sepsis. There was no evidence of pharmacokinetic interactions between paclitaxel and erlotinib; however, total carboplatin exposure trended higher in the presence of erlotinib. No consistent downstream effects on EGFR inhibition were found in skin. Durable objective responses were observed in non-small-cell lung and head and neck cancers.A dose level of erlotinib 125 mg combined with paclitaxel 225 mg/m(2) and carboplatin AUC 6 mg.min/mL is recommended for disease-directed studies. This phase I trial was followed by a randomized phase III study in non-small-cell lung cancer using a similar regimen.
Mast cells contribute to synovial inflammation in non-psoriatic and psoriatic spondyloarthritis
Authors: N. Yeremenko, T. Noordenbos, I. Gofita, P. P. Tak, J. D. Canete, D. Baeten
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background and objectives</h3> Comparative analyses of synovitis in spondyloarthritis (SpA) versus rheumatoid arthritis (RA) suggested that the innate immune system may play a predominant role in SpA pathogenesis. Based on this recent observation of marked synovial mast cell infiltration in psoriatic arthritis (PsA), the authors aimed to investigate the potential contribution of mast cells to synovial inflammation in SpA. <h3>Materials and methods</h3> Synovial tissue and fluid were obtained in non-psoriatic and psoriatic SpA (n=80) and RA (n=50). Synovial tissue was analysed by immunohistochemistry and double immunofluorescence. Synovial fluid was analysed by ELISA. Synovial tissue biopsies were also used for ex vivo cultures. <h3>Results</h3> In comparison with RA, synovial infiltration with c-kit positive mast cells was strongly and specifically increased in SpA independently of the subtype (non-psoriatic vs psoriatic), disease duration, and treatment. Staining of mast cell granules with tryptase and toluidine blue as well as analysis of synovial fluid levels of histamine and tryptase did not indicate increased degranulation in SpA synovitis. Mast cells expressed significantly more interleukin 17 (IL-17) in SpA than RA synovitis and constituted the major IL-17 expressing cell population in SpA synovitis. Targeting mast cells with the c-kit inhibitor imatinib mesylate in ex vivo tissue cultures led to a significant decrease in the production of IL-17 as well as other pro-inflammatory cytokines. Analysis of paired synovial biopsies before and after treatment indicated that this mast cell/IL-17 axis was not modulated by effective tumour necrosis factor (TNF) blockade in SpA. <h3>Conclusion</h3> The specific and TNF-independent increase of IL-17 expressing mast cell and the ex vivo targeting of these cells indicate that the mast cell/IL-17 axis may contribute to the synovial inflammation in peripheral SpA.
Chemotherapy, Bevacizumab, and Cetuximab in Metastatic Colorectal Cancer
Authors: Jolien Tol, Miriam Koopman, Annemieke Cats, Cees J. Rodenburg, Geert J.M. Creemers, Jolanda G. Schrama, Frans L.G. Erdkamp, Allert H. Vos, Cees J. van Groeningen, Harm A.M. Sinnige, Dirk J. Richel, Emile E. Voest, Jeroen R. Dijkstra, Marianne E. Vink-Börger, Ninja F. Antonini, Linda Mol, Johan H.J.M. van Krieken, Otilia Dalesio, Cornelis J.A. Punt
Journal: New England Journal of Medicine (2009)

Fluoropyrimidine-based chemotherapy plus the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab is standard first-line treatment for metastatic colorectal cancer. We studied the effect of adding the anti-epidermal growth factor receptor (EGFR) antibody cetuximab to a combination of capecitabine, oxaliplatin, and bevacizumab for metastatic colorectal cancer.We randomly assigned 755 patients with previously untreated metastatic colorectal cancer to capecitabine, oxaliplatin, and bevacizumab (CB regimen, 378 patients) or the same regimen plus weekly cetuximab (CBC regimen, 377 patients). The primary end point was progression-free survival. The mutation status of the KRAS gene was evaluated as a predictor of outcome.The median progression-free survival was 10.7 months in the CB group and 9.4 in the CBC group (P=0.01). Quality-of-life scores were lower in the CBC group. The overall survival and response rates did not differ significantly in the two groups. Treated patients in the CBC group had more grade 3 or 4 adverse events, which were attributed to cetuximab-related adverse cutaneous effects. Patients treated with cetuximab who had tumors bearing a mutated KRAS gene had significantly decreased progression-free survival as compared with cetuximab-treated patients with wild-type-KRAS tumors or patients with mutated-KRAS tumors in the CB group.The addition of cetuximab to capecitabine, oxaliplatin, and bevacizumab resulted in significantly shorter progression-free survival and inferior quality of life. Mutation status of the KRAS gene was a predictor of outcome in the cetuximab group. (ClinicalTrials.gov number, NCT00208546.)
Methotrexate in patients with moderate systemic lupus erythematosus (exclusion of renal and central nervous system disease)
Authors: S Gansauge, A Breitbart, N Rinaldi, M Schwarz-Eywill
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVES</h3> Methotrexate (MTX) has been used in several autoimmune diseases. Apart from its use in rheumatoid arthritis, MTX has been assessed in small studies in patients with vasculitis, uveitis, and inflammatory bowel disease. The aim of this study was to evaluate the efficacy of MTX in a particular group of patients with systemic lupus erythematosus (SLE). <h3>PATIENTS</h3> In an open prospective study 22 patients fulfilling the ACR criteria for SLE were included. Patients had one or more of the following manifestations: active non-destructive polyarthritis, dermatitis, vasculitis of the skin, pleuritis. All patients had been treated with corticosteroids for at least six months without achieving remission. Sixteen patients were taking antimalarial drugs in addition to corticosteroids, which were stopped at the beginning of the trial. Patients with renal and central nervous involvement were excluded from the study. All patients received MTX orally at a dose of 15 mg/week over six months. Corticosteroids were continued. As additional medication only indomethacin up to 100 mg/day was permitted if used before the start of the study. The outcome was evaluated using the SLE disease activity index (SLEDAI). <h3>RESULTS</h3> Disease activity was evaluated after six months of MTX treatment. All patients completed the study period. The SLEDAI decreased significantly from mean (SD) 12.2 (3.99) to 4 (3.75) (p=0.001). The prednisolone dose was reduced from a mean (SD) of 17.4 (12.8) at the beginning to 8.8 (5.36) mg/day at the end point of the study (p=0.01). MTX was well tolerated. Four patients complained of general malaise. Two patients had transient increases in liver enzymes. In no case did MTX have to be stopped. <h3>CONCLUSIONS</h3> In an open prospective study methotrexate was used in SLE patients with particular clinical characteristics. MTX was shown to be effective in reducing disease activity and sparing the dose of corticosteroids. Further controlled studies are necessary.
Characterization of probiotic Escherichia coli isolates with a novel pan-genome microarray
Authors: Hanni Willenbrock, Peter F Hallin, Trudy M Wassenaar, David W Ussery
Journal: Genome biology (2007)

Microarrays have recently emerged as a novel procedure to evaluate the genetic content of bacterial species. So far, microarrays have mostly covered single or few strains from the same species. However, with cheaper high-throughput sequencing techniques emerging, multiple strains of the same species are rapidly becoming available, allowing for the definition and characterization of a whole species as a population of genomes--the 'pan-genome'.Using 32 Escherichia coli and Shigella genome sequences we estimate the pan- and core genome of the species. We designed a high-density microarray in order to provide a tool for characterization of the E. coli pan-genome. Technical performance of this pan-genome microarray based on control strain samples (E. coli K-12 and O157:H7) demonstrated a high sensitivity and relatively low false positive rate. A single-channel analysis approach is robust while allowing the possibility for deriving presence/absence predictions for any gene included on our pan-genome microarray. Moreover, the array was highly sufficient to investigate the gene content of non-pathogenic isolates, despite the strong bias towards pathogenic E. coli strains that have been sequenced so far.This high-density microarray provides an excellent tool for characterizing the genetic makeup of unknown E. coli strains and can also deliver insights into phylogenetic relationships. Its design poses a considerably larger challenge and involves different considerations than the design of single strain microarrays. Here, lessons learned and future directions will be discussed in order to optimize design of microarrays targeting entire pan-genomes.
Combined aortic valve replacement and myocardial revascularization: results in 220 patients.
Authors: J V Richardson, N T Kouchoukos, J O Wright, R B Karp
Journal: Circulation (1979)

During a 7.5-year period ending in June 1977, 220 patients underwent combined aortic valve replacement and myocardial revascularization. Early (30-day) mortality was 5.4% (12 patients), and was significantly affected by the development of perioperative myocardial infarction. For 23 patients with electrocardiographic and enzymatic evidence for definite infarction, hospital mortality was 17%; for 66 patients with probable infarction mortality was 5%; and for 116 patients without evidence for infarction mortality was 3%. The difference in mortality between the definite and no infarction groups was significant (p less than 0.01). The incidence of perioperative infarction was influenced by the type of myocardial protection employed during the operative procedure. Definite infarction occurred in 24% of 41 patients who had mild (28-32 degrees C), intermittent hypothermic coronary perfusion, in 9% of 142 patients with hypothermic ischemic arrest (myocardial temperature 20 to 27 degrees C) and in none of 22 patients with hypothermic, potassium-induced cardioplegia (myocardial temperature 8--18 degrees C). The difference in the rate of infarction between the coronary perfusion and the two hypothermic ischemic arrest groups was significant (p less than 0.01). The mean duration of followup for 100% of the hospital survivors was 22.5 months. Cumulative survival was 88% at 1 year and 77% at 3 years. These figures do not differ significantly from those for patients without coronary artery disease having isolated aortic valve replacement in our institution, and are superior to those reported for patients with coronary and aortic valve disease undergoing only aortic valve replacement. We conclude that combined aortic valve replacement and myocardial revascularization should be performed in all patients in whom the lesions coexist. Hypothermic ischemic arrest, preferably in combination with potassium-induced cardioplegia, provides the most myocardial protection during operation.
Expression Profile of the Claudin Family mRNAs in Normal Human Bronchial Epithelial Cells
Authors: M. Kodama, K. Asano, T. Oguma, J. Miyata, K. Tomomatsu, H. Ogura, N. Horiuchi, S. Kagawa, S. Ueda, K. Sayama
Journal: Journal of Allergy and Clinical Immunology (2009)