tbuckley/cabot-search huggingface dataset:
A Phase 3 Trial of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis
Authors: Talmadge E. King, Williamson Z. Bradford, Socorro Castro-Bernardini, Elizabeth A. Fagan, Ian Glaspole, Marilyn K. Glassberg, Eduard Gorina, Peter M. Hopkins, David Kardatzke, Lisa Lancaster, David J. Lederer, Steven D. Nathan, Carlos A. Pereira, Steven A. Sahn, Robert Sussman, Jeffrey J. Swigris, Paul W. Noble
Journal: New England Journal of Medicine (2014)

In two of three phase 3 trials, pirfenidone, an oral antifibrotic therapy, reduced disease progression, as measured by the decline in forced vital capacity (FVC) or vital capacity, in patients with idiopathic pulmonary fibrosis; in the third trial, this end point was not achieved. We sought to confirm the beneficial effect of pirfenidone on disease progression in such patients.In this phase 3 study, we randomly assigned 555 patients with idiopathic pulmonary fibrosis to receive either oral pirfenidone (2403 mg per day) or placebo for 52 weeks. The primary end point was the change in FVC or death at week 52. Secondary end points were the 6-minute walk distance, progression-free survival, dyspnea, and death from any cause or from idiopathic pulmonary fibrosis.In the pirfenidone group, as compared with the placebo group, there was a relative reduction of 47.9% in the proportion of patients who had an absolute decline of 10 percentage points or more in the percentage of the predicted FVC or who died; there was also a relative increase of 132.5% in the proportion of patients with no decline in FVC (P<0.001). Pirfenidone reduced the decline in the 6-minute walk distance (P=0.04) and improved progression-free survival (P<0.001). There was no significant between-group difference in dyspnea scores (P=0.16) or in rates of death from any cause (P=0.10) or from idiopathic pulmonary fibrosis (P=0.23). However, in a prespecified pooled analysis incorporating results from two previous phase 3 trials, the between-group difference favoring pirfenidone was significant for death from any cause (P=0.01) and from idiopathic pulmonary fibrosis (P=0.006). Gastrointestinal and skin-related adverse events were more common in the pirfenidone group than in the placebo group but rarely led to treatment discontinuation.Pirfenidone, as compared with placebo, reduced disease progression, as reflected by lung function, exercise tolerance, and progression-free survival, in patients with idiopathic pulmonary fibrosis. Treatment was associated with an acceptable side-effect profile and fewer deaths. (Funded by InterMune; ASCEND ClinicalTrials.gov number, NCT01366209.).
Integrative analysis of array-comparative genomic hybridisation and matched gene expression profiling data reveals novel genes with prognostic significance in oesophageal adenocarcinoma
Authors: X. Y. Goh, J. R. E. Rees, A. L. Paterson, S. F. Chin, J. C. Marioni, V. Save, M. O'Donovan, P. P. Eijk, D. Alderson, B. Ylstra, C. Caldas, R. C. Fitzgerald
Journal: Gut (2011)

The incidence of oesophageal adenocarcinoma (OAC) has been increasing rapidly with a dismal survival rate of less than 20%. Understanding the genomic aberrations and biology of this cancer may enhance disease interventions. This study aimed to use genome-wide genomic and expression data to enhance the understanding of OAC pathogenesis and identify groups with differential outcomes.Array-comparative genomic hybridisation (aCGH) analysis was carried out on 56 fresh frozen OAC resection samples with long-term clinical follow-up data. Samples with aberrations were further analysed with whole-genome single-nucleotide polymorphism arrays to confirm aCGH findings. Matched gene expression microarray data were used to identify genes with high copy number-expression correlations. Nested-multiplex PCR on DNA from microdissected specimens and fluorescence in situ hybridisation assays were used for target validation. Immunohistochemistry on the same cohort and independent samples (n=371) was used for subsequent validation. Kaplan-Meier survival analyses were performed based on aCGH data after unsupervised K-means clustering (K=5, 50 iterations) and immunohistochemistry data.aCGH identified 17 common regions (>5% samples) of gains and 11 common regions of losses, including novel regions in OAC (loci 11p13 and 21q21.2). Integration of aCGH data with matched gene expression microarray data highlighted genes with high copy number-expression correlations: two deletions (p16/CDKN2A, MBNL1) and four gains (EGFR, WT1, NEIL2, MTMR9). Immunohistochemistry demonstrated protein over-expression of targets with gains: EGFR (10%), WT1 (20%), NEIL2 (14%) and MTMR9 (25%). These targets individually (p<0.060) and in combination had prognostic significance (p=0.008). On the genomic level, K-means clustering identified a cluster (32% of cohort) with differential log(2) ratios of 16 CGH probes (p<4×10(-7)) and a worse prognosis (median survival=1.37 years; p=0.015).Integration of aCGH and gene expression data identified copy number aberrations and novel genes with prognostic potential in OAC.
Reversal and prevention of airway response to antigen challenge by the inhaled leukotriene D4antagonist (L-648, 051) in patients with atopic asthma
Authors: J. B. Rasmussen, L.‐O. Eriksson, K.‐E. Andersson
Journal: Allergy (1991)

We examined the ability of the inhaled leukotriene D 4 antagonist (L‐648, 051) to inhibit antigen‐induced asthmatic responses. Twelve patients with stable exogenous asthma participated in two separate double‐blind, placebo‐controlled, cross‐over trials. The ability of the antagonist to reverse or inhibit antigen‐induced bronchoconstrictor response was examined; both the immediate and the late phases were studied. In the reversal study, patients inhaled 800 μ of L‐648, 051 during the immediate phase (15 min after antigen challenge) and again during in the late phase (7 h after antigen challenge). In the prevention study, the same dose (800 μ) of L‐648, 051 was inhaled before the expected immediate reaction (5 min before antigen challenge) as well as before the expected late reaction (2.5 h after antigen challenge). The LTD 4 antagonist was not effective in reversing the airway response to inhaled antigen, as measured by airway resistance (R t ), forced expiratory volume in 1 s (FEV 1 ) or forced vital capacity (FVC). When the antagonist was given prior to antigen challenge, a slight reduction in R 1 was observed during the immediate phase, but not during the late phase. Some improvement in FEV 1 and FVC during the immediate phase was also observed, but these changes did not reach statistical significance. These results suggest that LTD 4 plays a role in the immediate phase of antigen‐induced asthma.
Stages in development of mink cell focus-inducing (MCF) virus-accelerated leukemia in AKR mice.
Authors: P V O'Donnell, R Woller, A Chu
Journal: The Journal of Experimental Medicine (1984)

Flow cytometric techniques involving correlated dual parameter analysis of fluorescence and light scatter and transplantation bioassays were used to describe a series of cellular changes in thymus of young (1-4 mo old) AKR mice during development of mink cell focus-inducing (MCF) virus-accelerated leukemia. Three stages of leukemogenesis were defined before appearance of frankly leukemic mice. Stage 1, apparent 28-40 d after injection of MCF 69L1 virus, represented steady-state infection of thymocytes by MCF virus without apparent change in light scatter properties of the cells or in expression of alloantigens Thy-1, Lyt-1, Lyt-2, L3T4a, B2A2, or H-2K on the major thymocyte subpopulations. Expression of MCF virus was highest in the population of small cortical thymocytes. Stage II was observed at highest frequency 50-60 d postinjection and represented the emergence of a clonal population of cells with transformed properties which could be resolved from normal thymocytes by light scatter and expression of B2A2, H-2K, and gp70 antigens. Stage III was observed at highest frequency at 70 d postinjection, when considerable enlargement of thymus had occurred, and appeared to represent the outgrowth of fully transformed cells that replaced the normal thymocyte subpopulations. The alloantigen phenotype of blast cells from frankly leukemic mice did not differ qualitatively from that of stage II or stage III cells but displayed considerable heterogeneity with respect to quantitative expression of alloantigens and gp70. At least two populations of leukemic blasts could be resolved in the majority of primary thymomas analyzed. It is unclear whether these populations represent the outgrowth of independent clones of transformed cells or if they are related in some way. Our data are consistent with MCF virus-induced transformation of cells in the lineage to small peanut agglutinin-positive, cortisone-sensitive thymocytes, a subpopulation that predominates in the thymus and which is thought to be destined for cell death in situ.
The Efficacy of Brain Natriuretic Peptide Levels in Differentiating Constrictive Pericarditis From Restrictive Cardiomyopathy
Authors: Ferdinand S. Leya, Dinesh Arab, Dominique Joyal, Krystyna M. Shioura, Bruce E. Lewis, Lowell H. Steen, Leslie Cho
Journal: Journal of the American College of Cardiology (2005)
Segment Length and Risk for Neoplastic Progression in Patients with Barrett Esophagus
Authors: RE Rudolph, TL Vaughan, B Storer
Journal: Annals of Internal Medicine (2000)

Letters7 November 2000Segment Length and Risk for Neoplastic Progression in Patients with Barrett EsophagusRebecca E. Rudolph, MD, MPH, Thomas L. Vaughan, MD, MPH, and Barry Storer, PhDRebecca E. Rudolph, MD, MPHFred Hutchinson Cancer Research Center; Seattle, WA 98109-1024 (Rudolph, Vaughan, Storer)Search for more papers by this author, Thomas L. Vaughan, MD, MPHFred Hutchinson Cancer Research Center; Seattle, WA 98109-1024 (Rudolph, Vaughan, Storer)Search for more papers by this author, and Barry Storer, PhDFred Hutchinson Cancer Research Center; Seattle, WA 98109-1024 (Rudolph, Vaughan, Storer)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-133-9-200011070-00026 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Assessment of confounding in these analyses was relatively straightforward because none of the risk factors that we examined, with the exception of histologic diagnosis at baseline, was associated to an important degree with both risk for neoplastic progression and segment length at baseline. After it was clear that histologic diagnosis at baseline was a confounder, we evaluated the effects of other potential risk factors by inserting them one or two at a time into a model that also included segment length and histologic diagnosis at baseline. None of these factors was observed to change the relative risk estimate ... Author, Article, and Disclosure InformationAffiliations: Fred Hutchinson Cancer Research Center; Seattle, WA 98109-1024 (Rudolph, Vaughan, Storer) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoEffect of Segment Length on Risk for Neoplastic Progression in Patients with Barrett Esophagus Rebecca E. Rudolph , Thomas L. Vaughan , Barry E. Storer , Rodger C. Haggitt , Peter S. Rabinovitch , Douglas S. Levine , and Brian J. Reid Segment Length and Risk for Neoplastic Progression in Patients with Barrett Esophagus Hashem B. El-Serag Metrics Cited ByDots, lines, contours, and ends: An image-based review of esophageal pathologyAssociation Between Length of Barrett's Esophagus and Risk of High-grade Dysplasia or Adenocarcinoma in Patients Without DysplasiaAvaliação da expressão imunoistoquímica da proteína p16INK4a no adenocarcinoma de esôfagoThree-Tiered Risk Stratification Model to Predict Progression in Barrett's Esophagus Using Epigenetic and Clinical FeaturesSection I: Epidemiological review 7 November 2000Volume 133, Issue 9Page: 748KeywordsCohort studiesEsophageal adenocarcinomaEsophagusFactor analysisMedical risk factorsMultivariate analysisRelative risk ePublished: 7 November 2000 Issue Published: 7 November 2000 CopyrightCopyright © 2000 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Protease inhibitors of the sulfonamide type: Anticancer, antiinflammatory, and antiviral agents
Authors: Claudiu T. Supuran, Angela Casini, Andrea Scozzafava
Journal: Medicinal Research Reviews (2003)

The sulfonamides constitute an important class of drugs, with several types of pharmacological agents possessing antibacterial, anticarbonic anhydrase, diuretic, hypoglycemic, and antithyroid activity among others. A large number of structurally novel sulfonamide derivatives have ultimately been reported to show substantial protease inhibitory properties. Of particular interest are some metalloprotease inhibitors belonging to this class, which by inhibiting several matrix metalloproteases (MMPs) show interesting antitumor properties. Some of these compounds are currently being evaluated in clinical trials. The large number of sulfonamide MMP inhibitors ultimately reported also lead to the design of effective tumor necrosis factor-alpha converting enzyme (TACE) inhibitors, potentially useful in the treatment of inflammatory states of various types. Since both MMPs and TACE contribute synergistically to the pathophysiology of many diseases, such as arthritis, bacterial meningitis, tumor invasion; the dual inhibition of these enzymes emerged as an interesting target for the drug design of anticancer/antiinflammatory drugs, and many such sulfonamide derivatives were recently reported. Human neutrophyl elastase (HNE) inhibitors of the sulfonamide type may also be useful in the treatment of inflammatory conditions, such as emphysema, cystic fibrosis, chronic bronchitis, ischemia reperfusion injury, and acute respiratory distress syndrome. Inhibition of some cysteine proteases, such as several caspase and cathepsin isozymes, may lead to the development of pharmacological agents effective for the management of several diseases, such as rheumatoid arthritis, inflammatory bowel disease, brain damage, and stroke. Another research line that progressed much in the last time regards different sulfonamides with remarkable antiviral activity. Some clinically used HIV protease inhibitors (such as amprenavir) possess sulfonamide moieties in their molecules, which are critical for the potency of these drugs, as shown by means of X-ray crystallography, whereas a very large number of other derivatives are constantly being synthesized and evaluated in order to obtain compounds with lower toxicity or augmented activity against viruses resistant to the such first generation drugs. Other viral proteases, such as those isolated from several types of herpes viruses may be inhibited by sulfonamide derivatives, leading thus to more effective classes of antiviral drugs.
Combining gemcitabine, oxaliplatin and capecitabine (GEMOXEL) for patients with advanced pancreatic carcinoma (APC): a phase I/II trial
Authors: V. Hess, S. Pratsch, S. Potthast, L. Lee, R. Winterhalder, L. Widmer, C. Cescato, A. Lohri, L. Jost, P. Stillhart, B. Pestalozzi, R. Herrmann
Journal: Annals of Oncology (2010)
How fast is fast enough? An audit and league table of response times of acute hospital NHS Trust switchboards in England
Authors: Kayvan Shokrollahi, Sujatha Tadiparthi, Sathish Jayagopal
Journal: Journal of the Royal Society of Medicine (2008)

To audit response times by all acute NHS hospital switchboards in England for external incoming calls. As with any audit, we set out to draw attention to efficiencies and deficiencies in the system, highlight problems, and suggest the first steps towards improving standards in a very important and poorly acknowledged part of our healthcare system.Telephone calls were made to hospital switchboards, and time to response was measured. The results were then audited.Acute hospital NHS Trust switchboards in England.Time to response by hospital switchboards. The target time was 20 seconds.Only 36% of 219 hospital switchboards met the 20 second target, with the average answering time across all switchboards being 45 seconds. The best performer was University Hospital North Durham (mean = 1 second) and the worst Bristol Royal Infirmary (mean = 381 seconds). We found that automated answer systems substantially increase the answer time to an operator; the fastest automated service was at Princess Royal University Hospital, which was ranked 69th.We recommend a formal NHS-wide audit system for switchboard response times.
Neck Circumference and the Development of Cardiovascular Disease Risk Factors in the Framingham Heart Study
Authors: Sarah Rosner Preis, Michael J. Pencina, Ralph B. D’Agostino, James B. Meigs, Ramachandran S. Vasan, Caroline S. Fox
Journal: Diabetes Care (2012)

Upper-body subcutaneous adipose tissue, estimated by neck circumference (NC), is a unique fat depot that may confer additional risk for metabolic risk factors over generalized and central adiposity (1). Using a prospective study design, we now evaluate whether NC improves the prediction of incident cardiovascular disease risk factors over BMI and waist circumference (2).

Framingham Heart Study participants ( n = 2,732; 54% women; mean age, 57 years) were followed for ∼10 years (1995–2008) for the development of type 2 diabetes (fasting plasma glucose ≥126 mg/dL or treatment), hypertension, low HDL cholesterol (<40 mg/dL, men; <50 mg/dL, women), and high triglycerides (≥150 mg/dL or lipid treatment). NC, BMI, and waist circumference were standardized within each sex to a mean of zero and an SD of one. Logistic regression models, adjusted for age, sex, and smoking, were used to test the association between 1 SD increment of NC with each outcome. …
Association of Gly972Arg polymorphism of IRS1 gene with type 2 diabetes mellitus in lean participants of a national health survey in Mexico: a candidate gene study
Authors: Ana I. Burguete-Garcia, Miguel Cruz-Lopez, Vicente Madrid-Marina, Ruy Lopez-Ridaura, Mauricio Hernández-Ávila, Bernardo Cortina, Rosa E. Gómez, Eduardo Velasco-Mondragón
Journal: Metabolism (2009)
Analysis of systolic bulging. Mechanical characteristics of acutely ischemic myocardium in the conscious dog.
Authors: M Akaishi, W S Weintraub, R M Schneider, L W Klein, J B Agarwal, R H Helfant
Journal: Circulation Research (1986)

To determine the mechanical factors affecting regional segmental motion after acute coronary occlusion, we studied seven conscious dogs, instrumented with sonomicrometers. Loading conditions were changed by the withdrawal of 500 ml of blood and the transfusion of 800 ml of blood. To express segmental motion, percent systolic shortening, percent systolic elongation, and early diastolic shortening were calculated. Blood withdrawal decreased left ventricular preload, increased percent systolic elongation (from 6.9 +/- 3.1% to 9.9 +/- 3.5%) and early diastolic shortening (12.9 +/- 5.3% to 16.6 +/- 5.3%), and decreased percent systolic shortening. Blood transfusion increased left ventricular preload, decreased percent systolic elongation (to 5.2 +/- 1.8%) and early diastolic shortening (8.8 +/- 2.9%), and increased percent systolic shortening. Manipulation of loading did not change regional myocardial blood flow. In acutely ischemic myocardium, the tension-length loop showed an exponential upstroke during isovolumic systole and a nearly superimposed exponential downstroke during the isovolumic relaxation phase after systole, compatible with essentially passive movement as seen with an elastic material. The changes in loading conditions affected the tension-length curve to a very minor extent. The uniformity of the curve and its exponential shape explain the load-dependency of systolic bulging and segmental motion. It is concluded that systolic bulging depends on the change in the preload tension due to the compliant portion of tension-length curve, and that shortening of ischemic myocardium during the isovolumic relaxation phase is a completely passive phenomenon.
Biopsy documented idiopathic interstitial pneumonias - Analysis of diagnostic yield, survival and mortality over 9 years
Authors: Nitin Abhyankar, Vrushali Khadke, Jayshree Jain, Ajit Tambolkar, Rahul Kubde
Journal: European Respiratory Journal (2013)

Material and Methods  -78 patients underwent lung biopsy using medical thoracoscopy between 2004 till 2013.All cases had restriction on Spirometry, bilateral interstitial infiltrates,exertional dyspnoea and radiological features either nonclassical for UIP (70/78 cases) or possible UIP(8/78 cases). Results - 37/ 78 (47.43%) patients had 9UIP9 IPF after biopsy and multidisciplinary discussion (also further validated on clinical and radiological follow up). 41/78 patients had 9non UIP9 pattern.  Comparisons revealed younger patients (52.9 years vs 60.47 years),and longer average survival (41.34 months vs 27 months) in 9non UIP9 group.( statistically not significant). Non UIP group had 6 deaths whereas UIP group had 20 deaths  ( p = 0.01).  17/37 patients in the 9UIP9 group never received pirfenidone. 20 patients received pirfenidone for some duration.Average survival in 9pirfenidone9 group was 32.9 months vs 20.06 months in 9no pirfenidone9 group.(statistically not significant) .15 patient in 9no pirfenidone9 group died vs 5 deaths in 9pirfenidone9 group  (p=0.4801) .  Conclusions  - 1) 47 % of lung biopsies in patients with IIP with radiological pattern not classical for UIP IPF have UIP on histopathology and clinical behaviour. 2) Non UIP diagnosis seem to be associated with younger age and better survival duration than UIP. Mortality for UIP is significantly higher than Non UIP pattern. 3) Pirfenidone may be improving survival in UIP IPF.
BCR-ABL nuclear entrapment kills human CML cells: ex vivo study on 35 patients with the combination of imatinib mesylate and leptomycin B
Authors: Alessandra Aloisi, Sandra Di Gregorio, Fabio Stagno, Patrizia Guglielmo, Francesca Mannino, Maria Pia Sormani, Paolo Bruzzi, Carlo Gambacorti-Passerini, Giuseppe Saglio, Salvatore Venuta, Rosario Giustolisi, Angelo Messina, Paolo Vigneri
Journal: Blood (2005)
A Nationwide Cohort Study of Stage I Seminoma Patients Followed on a Surveillance Program
Authors: Mette Saksø Mortensen, Jakob Lauritsen, Maria Gry Gundgaard, Mads Agerbæk, Niels Vilstrup Holm, Ib Jarle Christensen, Hans von der Maase, Gedske Daugaard
Journal: European Urology (2014)