tbuckley/cabot-search huggingface dataset:
Efficacy of Gefitinib, an Inhibitor of the Epidermal Growth Factor Receptor Tyrosine Kinase, in Symptomatic Patients With Non–Small Cell Lung Cancer
Authors: Mark G. Kris, Ronald B. Natale, Roy S. Herbst, Thomas J. Lynch, Jr, Diane Prager, Chandra P. Belani, Joan H. Schiller, Karen Kelly, Harris Spiridonidis, Alan Sandler, Kathy S. Albain, David Cella, Michael K. Wolf, Steven D. Averbuch, Judith J. Ochs, Andrea C. Kay
Journal: JAMA (2003)

More persons in the United States die from non-small cell lung cancer (NSCLC) than from breast, colorectal, and prostate cancer combined. In preclinical testing, oral gefitinib inhibited the growth of NSCLC tumors that express the epidermal growth factor receptor (EGFR), a mediator of cell signaling, and phase 1 trials have demonstrated that a fraction of patients with NSCLC progressing after chemotherapy experience both a decrease in lung cancer symptoms and radiographic tumor shrinkages with gefitinib.To assess differences in symptomatic and radiographic response among patients with NSCLC receiving 250-mg and 500-mg daily doses of gefitinib.Double-blind, randomized phase 2 trial conducted from November 2000 to April 2001 in 30 US academic and community oncology centers. Patients (N = 221) had either stage IIIB or IV NSCLC for which they had received at least 2 chemotherapy regimens.Daily oral gefitinib, either 500 mg (administered as two 250-mg gefitinib tablets) or 250 mg (administered as one 250-mg gefitinib tablet and 1 matching placebo).Improvement of NSCLC symptoms (2-point or greater increase in score on the summed lung cancer subscale of the Functional Assessment of Cancer Therapy-Lung [FACT-L] instrument) and tumor regression (>50% decrease in lesion size on imaging studies).Of 221 patients enrolled, 216 received gefitinib as randomized. Symptoms of NSCLC improved in 43% (95% confidence interval [CI], 33%-53%) of patients receiving 250 mg of gefitinib and in 35% (95% CI, 26%-45%) of patients receiving 500 mg. These benefits were observed within 3 weeks in 75% of patients. Partial radiographic responses occurred in 12% (95% CI, 6%-20%) of individuals receiving 250 mg of gefitinib and in 9% (95% CI, 4%-16%) of those receiving 500 mg. Symptoms improved in 96% of patients with partial radiographic responses. The overall survival at 1 year was 25%. There were no significant differences between the 250-mg and 500-mg doses in rates of symptom improvement (P =.26), radiographic tumor regression (P =.51), and projected 1-year survival (P =.54). The 500-mg dose was associated more frequently with transient acne-like rash (P =.04) and diarrhea (P =.006).Gefitinib, a well-tolerated oral EGFR-tyrosine kinase inhibitor, improved disease-related symptoms and induced radiographic tumor regressions in patients with NSCLC persisting after chemotherapy.
Effects of mandibular advancement on respiratory resistance
Authors: AM Lorino, M Maza, MP d'Ortho, A Coste, A Harf, H Lorino
Journal: European Respiratory Journal (2000)

Mandibular advancing devices are proposed as nonsurgical treatment for certain patients with an obstructive sleep apnoea syndrome. Since they act by increasing the upper airway calibre, the aim of the present study was to investigate the changes in respiratory resistance (Rrs) resulting from mandibular advancement. Rrs was measured at the nose by the forced oscillation technique (4-32 Hz). Ten normal subjects were studied under three conditions: resting mandibular position, passive mandibular advancement steadied by a wax bite, and voluntary advancement, in random order. Respiratory resistance was extrapolated to 0 Hz (R0) and estimated at 16 Hz (R16) by linear regression analysis of respiratory resistive impedance versus frequency. R0 (mean+/-SEM=3.5+/-0.2 cmH2O x L(-1) x s in the resting position) decreased significantly with passive advancement (2.9+/-0.2 cmH2O x L(-1) x s, p&lt;0.001), but remained unchanged with voluntary mandibular advancement (3.6+/-0.2 cmH2O x L(-1) s). Similar results were obtained for R16. The results of this study demonstrate that the effects of mandibular advancement on upper airway resistance differ, depending on whether advancement is passive or active, and suggest that in order to simulate the actual effects of therapeutic devices, mandibular advancement should be passive.
Successful treatment of psoriatic arthritis with rituximab
Authors: J D Cohen
Journal: Annals of the Rheumatic Diseases (2008)

Rituximab is a chimeric human/mouse monoclonal anti-CD20 antibody approved for the treatment of rheumatoid arthritis (RA) refractory to anti-tumour necrosis factor (TNF) therapy.1 Rituximab seems to be efficient in other diseases such as autoimmune cytopoenia,2 systemic lupus erythaematosus (SLE),3 dermatomyositis4 and Sjogren syndrome.5 To our knowledge, no case of psoriatic arthritis (PsA) treated by rituximab has been reported. Nevertheless, a partial remission of psoriasis following rituximab therapy for non-Hodgkin’s lymphoma has been reported.6 We describe the case of a man with severe PsA with dramatic improvement after rituximab treatment.

A 62-year-old Caucasian male had PsA since 2001 with asymmetrical arthritis involving distal interphalangeal arthritis, wrist, knee and ankle joint, and dactylitis. He has a personal (15 years ago) and …
Silver/silver chloride electrodes for measurement of potential difference in human bronchi
Authors: I. Fajac, J. Lacronique, A. Lockhart, J. Dall'Ava-Santucci, D. J Dusser
Journal: Thorax (1998)

<h3>BACKGROUND</h3> An easy and reliable method to measure potential difference (PD) in the lower airways would be of interest in the field of cystic fibrosis. We have developed silver/silver chloride (Ag/AgCl) electrodes to measure PD in the lower airways. <h3>METHODS</h3> To validate this technique the nasal PD measured with Ag/AgCl electrodes and with conventional perfused electrodes was compared in 16 patients. The range of PD measured with Ag/AgCl electrodes in the lower airways during fibreoptic bronchoscopy was determined in 14 adult patients and in nine the reproducibility of this technique was examined. <h3>RESULTS</h3> Nasal PD values measured with Ag/AgCl and perfused electrodes were highly correlated (<i>r</i> = 0.985, p&lt;0.0001) and the limits of agreement (mean ±2SD of the difference) between the two methods were –1.91 mV and 1.53 mV. In the lower airways a progressive and slight decrease in PD values with decreasing airway diameter was observed in most patients. The mean (2SD) of the differences between the two tracheal measurements was 0.21 (1.73) mV. <h3>CONCLUSIONS</h3> The use of Ag/AgCl electrodes gives a reliable and reproducible measurement of PD in the lower airways in humans.
Characteristics of Food Allergic Reactions in a Multi-Center Observational Study (CoFAR2) of Food Allergy
Authors: D.M. Fleischer, S.M. Jones, J. Ullah, D. Stablein, R.A. Wood, A.W. Burks, A.H. Liu, D.Y. Leung, R. Lindblad, H.A. Sampson
Journal: Journal of Allergy and Clinical Immunology (2009)
Character analysis and the integration of molecular and morphological data in an understanding of sand dollar phylogeny.
Authors: C R Marshall
Journal: Molecular Biology and Evolution (1992)

Reconciling discordant morphological and molecular phylogenies remains a problem in modern systematics. By examining conflicting DNA-hybridization and morphological phylogenies of sand dollars, I show that morphological criteria may be used to help evaluate the reliability of molecular phylogenies where they differ from morphological trees. All available criteria for assessing the reliability of DNA-hybridization phylogenies suggest that the sand dollar DNA-hybridization phylogeny is robust. Standard homology-recognition criteria are used to assess the a priori reliabilities of the morphological attributes associated with the node drawn into question by the DNA data, and it is shown that these attributes are among the least phylogenetically informative of all the morphological characters. Moreover, the questioned node has the smallest number of supporting characters, and most of these characters are associated with the food grooves, which suggests that they may be functionally correlated. Thus, on the basis of the analysis of the morphological data and given the robustness of the DNA tree, the DNA phylogeny is preferred. Further, paleobiogeographic data support the DNA tree rather than the morphological tree, and a plausible heterochronic mechanism has been proposed that may account for the homoplasious morphological evolution that must have occurred if the DNA tree is correct.
Tumor-Specific Methylation in Bronchial Lavage for the Early Detection of Non-Small-Cell Lung Cancer
Authors: Hojoong Kim, Young Mi Kwon, Jin Seuk Kim, Haengbyoung Lee, Jung-Ho Park, Young Mog Shim, Joungho Han, Joobae Park, Duk-Hwan Kim
Journal: Journal of Clinical Oncology (2004)

Purpose The aim of this study was to identify tumor-specific methylation in bronchial lavage for the early detection of non-small-cell lung cancer (NSCLC) by differentiating the age-related methylation from the tumor-specific methylation in NSCLC. Patients and Methods Eighty-five NSCLC patients and 127 cancer-free subjects participated in this study. Aberrant methylation at the promoters of the p16, Ras association domain family 1A (RASSF1A), fragile histidine triad (FHIT), H-cadherin, and retinoic acid receptor β (RARβ) genes were evaluated in the resected tumor tissues and bronchial lavage samples of NSCLC patients and in the bronchial lavage samples of cancer-free subjects by methylation-specific polymerase chain reaction. Results Of the 127 cancer-free samples, methylation was detected in 6% for p16, 13% for RARβ, 3% for H-cadherin, 4% for RASSF1A, and 28% for FHIT. Hypermethylation of the p16, RARβ, H-cadherin, and RASSF1A genes was not associated with patient age and smoking, whereas hypermethylation of the FHIT promoter occurred more frequently in older patients (P = .02) and was associated with exposure to tobacco smoke (P = .001). A strong correlation between age and smoking was found in patients with hypermethylation of the FHIT gene (r = 0.36; P = .03). A total of 68% of the bronchial lavage samples from the 85 NSCLC patients showed methylation of at least one of p16, RARβ, H-cadherin, and RASSF1A genes. Conclusion Our study suggests that tumor-specific methylation of the p16, RASSF1A, H-cadherin, and RARβ genes may be a valuable biomarker for the early detection of NSCLC in bronchial lavage, and that the age-related methylation of FHIT gene in the normal bronchial epithelium is related to the exposure to tobacco smoke.
Interim analysis of post-marketing surveillance of omalizumab in Japan
Authors: Ken Ohta, Hajime Yoshisue, Yasuo Aoki, Takuro Irokawa, Masahide Ishigaki, Mitsuru Adachi, Terumasa Miyamoto
Journal: European Respiratory Journal (2013)

Background: Omalizumab (OMA) was launched as an add-on therapy for patients with uncontrolled severe allergic asthma in Japan in March 2009, at which point post-marketing surveillance began.

Methods: All patients prescribed OMA are entered into a prospective, real-life surveillance registry, and are followed up to assess outcomes (adverse events, exacerbations, response by physician’s Global Evaluation of Treatment Effectiveness [GETE], lung function, rescue medication use) over 1 year. We present an interim analysis in patients who have completed at least 4 months of observation.

Results: Safety (n=1,259): Adverse reactions occurred in 7.7%, most frequently involving the skin and subcutaneous tissue (2.2%). One case of suspected anaphylaxis was reported (0.08%), but an anti-OMA antibody test was negative.

Efficacy (n=1,049): Asthma exacerbations were significantly decreased following the initiation of OMA. Response by physician’s GETE was 60% after 4 months of treatment. Morning and evening peak expiratory flow rate were increased, and rescue medication use was reduced, compared with baseline (all p<0.001).

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Conclusions: This interim analysis suggests that OMA is well tolerated and associated with clinical benefit in Japanese patients. Surveillance is ongoing, and future analyses will continue to provide information on the use of OMA in Japan.
Community-Wide Cardiovascular Disease Prevention Programs and Health Outcomes in a Rural County, 1970-2010
Authors: N. Burgess Record, Daniel K. Onion, Roderick E. Prior, David C. Dixon, Sandra S. Record, Fenwick L. Fowler, Gerald R. Cayer, Christopher I. Amos, Thomas A. Pearson
Journal: JAMA (2015)

IMPORTANCE Few comprehensive cardiovascular risk reduction programs, particularly those in rural, low-income communities, have sustained community-wide interventions for more than 10 years and demonstrated the effect of risk factor improvements on reductions in morbidity and mortality.OBJECTIVE To document health outcomes associated with an integrated, comprehensive cardiovascular risk reduction program in Franklin County, Maine, a low-income rural community.DESIGN, SETTING, AND PARTICIPANTS Forty-year observational study involving residents of Franklin County, Maine, a rural, low-income population of 22 444 in 1970, that used the preceding decade as a baseline and compared Franklin County with other Maine counties and state averages.INTERVENTIONS Community-wide programs targeting hypertension, cholesterol, and smoking, as well as diet and physical activity, sponsored by multiple community organizations, including the local hospital and clinicians.MAIN OUTCOMES AND MEASURES Resident participation; hypertension and hyperlipidemia detection, treatment, and control; smoking quit rates; hospitalization rates from 1994 through 2006, adjusted for median household income; and mortality rates from 1970 through 2010, adjusted for household income and age.RESULTS More than 150 000 individual county resident contacts occurred over 40 years.Over time, as cardiovascular risk factor programs were added, relevant health indicators improved.Hypertension control had an absolute increase of 24.7% (95% CI, 21.6%-27.7%)from 18.3% to 43.0%, from 1975 to 1978; later, elevated cholesterol control had an absolute increase of 28.5% (95% CI, 25.3%-31.6%)from 0.4% to 28.9%, from 1986 to 2010.Smoking quit rates improved from 48.5% to 69.5%, better than state averages (observed -expected [O -E], 11.3%; 95% CI, 5.5%-17.7%;P < .001),1996-2000; these differences later disappeared when Maine's overall quit rate increased.Franklin County hospitalizations per capita were less than expected for the measured period, 1994-2006 (O -E, -17 discharges/1000 residents; 95% CI -20.1 to -13.9; P < .001).Franklin was the only Maine county with consistently lower adjusted mortality than predicted over the time periods 1970-1989 and 1990-2010 (O -E, -60.4 deaths/100 000; 95% CI, -97.9 to -22.8; P < .001,and -41.6/100 000; 95% CI, -77.3 to -5.8; P = .005,respectively).CONCLUSIONS AND RELEVANCE Sustained, community-wide programs targeting cardiovascular risk factors and behavior changes to improve a Maine county's population health were associated with reductions in hospitalization and mortality rates over 40 years, compared with the rest of the state.Further studies are needed to assess the generalizability of such programs to other US county populations, especially rural ones, and to other parts of the world.
Effect of exercise on lung-perfusion scanning in patients with bronchogenic carcinoma
Authors: B. Chenuel, P. Haouzi, P. Olivier, P.Y. Marie, B. Chalon, J. Borrelly
Journal: European Respiratory Journal (2002)

The aim of this study was to determine whether perfusion-scintillation scanning, used as a predictive pre-operative index of lung functionality in patients with lung cancer, is affected by the level of pulmonary blood flow (PBF). Twenty patients with primary lung cancer underwent spirometry and a radionuclide-perfusion scan (macroaggregated albumin particles labelled with 99m Technetium) both at rest and during the last minute of a ramp-like increase in work rate until exhaustion. On average, the perfusion of the lung with the tumour was significantly reduced by the same magnitude at rest and during exercise (mean±sd: −9±6% versus −10±4% of the cardiac output), regardless of the extent of the tumour. However, subject-by-subject analysis revealed that in two patients, a larger decrease in the perfusion of the lung with the tumour was observed during exercise than at rest (−11% and −17%, respectively). This leads to an underestimation of predictive postoperative functional parameters if resting values are used in these patients. The use of perfusion scintigraphy at rest therefore gives a clear picture of the functionality of the lung before resection in most patients requiring surgery.
Widening of the Excitable Gap During Pharmacological Cardioversion of Atrial Fibrillation in the Goat
Authors: Maurits C. E. F. Wijffels, Rick Dorland, Frans Mast, Maurits A. Allessie
Journal: Circulation (2000)

Background —Previous studies suggest that the antifibrillatory action of class I and III drugs is due to prolongation of the atrial wavelength. The aim of the present study was to directly evaluate the electrophysiological action of antifibrillatory drugs in a goat model of chronic atrial fibrillation (AF). Methods and Results —Six goats were instrumented with multiple atrial electrodes, and sustained AF was induced by electrical remodeling. During sustained AF, the effects of intravenous infusion of cibenzoline, hydroquinidine, flecainide, and d -sotalol on AF cycle length (AFCL), refractory period (RP AF ), conduction velocity (CV AF ), pathlength (PL AF ), wavelength (WL AF ), temporal (AFCL−RP AF ), and spatial (PL AF −WL AF ) excitable gap were studied. The RP AF was measured by determining the earliest moment at which single stimuli could capture the fibrillating atria. CV AF was measured during regional entrainment of AF. Contrary to our expectation, cardioversion of AF could not be attributed to prolongation of WL AF . Hydroquinidine and d -sotalol did not affect WL AF significantly, whereas cibenzoline and flecainide even shortened WL AF by 18% and 36%, respectively. PL AF was increased by hydroquinidine and d -sotalol by 30%, whereas cibenzoline and flecainide did not prolong PL AF . The only parameter that correlated consistently with cardioversion of AF was a widening of the temporal excitable gap (cibenzoline 176%, hydroquinidine 105%, flecainide 86%, d -sotalol 88%). Conclusions —Pharmacological cardioversion of AF cannot be explained by prolongation of WL AF . An alternative explanation for the antifibrillatory effect of class I and III drugs may be a widening of the temporal excitable gap.
Malaria: Mechanisms of Erythrocytic Infection and Pathological Correlates of Severe Disease
Authors: Kasturi Haldar, Sean C. Murphy, Dan A. Milner, Terrie E. Taylor
Journal: Annual Review of Pathology Mechanisms of Disease (2006)

Malaria is an ancient disease that continues to cause enormous human morbidity and mortality. The life cycle of the causative parasite involves multiple tissues in two distinct host organisms, mosquitoes and humans. However, all the clinical symptoms of malaria are a consequence of infection of human erythrocytes. An understanding of the basic mechanisms that govern parasite invasion, remodeling, growth, and reinvasion of erythrocytes and the complex events leading to tissue pathology may yield new diagnostics and treatments for malaria. This approach is revealing a more complete picture of the most serious syndrome associated with this infection—cerebral malaria. We focus on the most recent understanding of the molecular basis of infection, summarize our finding from an ongoing pediatric cerebral malaria autopsy study in Malawi, and integrate these insights to malarial pathology.
Visualizing Regional Myocardial Blood Flow in the Mouse
Authors: Melissa A. Krueger, Sabine S. Huke, Robb W. Glenny
Journal: Circulation Research (2013)

Rationale: The spatial distribution of blood flow in the hearts of genetically modified mice is a phenotype of interest because derangements in blood flow may precede detectable changes in organ function. However, quantifying the regional distribution of blood flow within organs of mice is challenging because of the small organ volume and the high resolution required to observe spatial differences in flow. Traditional microsphere methods in which the numbers of microspheres per region are indirectly estimated from radioactive counts or extracted fluorescence have been limited to larger organs for 2 reasons; to ensure statistical confidence in the measured flow per region and to be able to physically dissect the organ to acquire spatial information. Objective: To develop methods to quantify and statistically compare the spatial distribution of blood flow within organs of mice. Methods and Results: We developed and validated statistical methods to compare blood flow between regions and with the same regions over time using 15-µm fluorescent microspheres. We then tested this approach by injecting fluorescent microspheres into isolated perfused mice hearts, determining the spatial location of every microsphere in the hearts, and then visualizing regional flow patterns. We demonstrated application of these statistical and visualizing methods in a coronary artery ligation model in mice. Conclusions: These new methods provide tools to investigate the spatial and temporal changes in blood flow within organs of mice at a much higher spatial resolution than currently available by other methods.
Crohn's ileitis after liver transplantation from a living related donor with Crohn's disease
Authors: K A Papadakis, R Matuk, M T Abreu, E A Vasiliauskas, P R Fleshner, J Lechago, T Tran, F F Poordad, P Martin, J Vierling, S R Targan
Journal: Gut (2004)

We read with interest the case described by Sonwalkar et al of a patient who developed fulminant Crohn’s colitis after allogeneic stem cell transplantation (ASCT) ( Gut 2003; 52 :1518–21). Although the donor had no known Crohn’s disease (CD) and did not carry the IBD3 or IBD5 haplotypes associated with CD, HLA class III mismatches at IBD3 and a CD associated polymorphism of the 5′UTR of NOD2/CARD15 were present in the donor and in the reconstituted immune cell population of the recipient post ASCT. The authors hypothesised that adoptive transfer of CD susceptibility may have occurred between ACST donor and recipient.

Herein, we report a case of a patient who developed CD after receiving a living related liver transplant from a donor with known CD. A 24 year old female received a liver transplant from a living related donor for decompensated …
A roadmap for integrating the brain with mind maps
Authors: Andreas Demetriou, Antigoni Mouyi
Journal: Behavioral and Brain Sciences (2007)

Abstract This commentary compares the P-FIT model with psychometric and developmental models of intelligence and shows that there are isomorphisms and divergences between them. All three models involve some common dimensions, but the P-FIT model lacks many of the dimensions of the other models. Then we point to research that can lead to the integration of brain models with cognitive-developmental models.