tbuckley/cabot-search huggingface dataset:
Can non-invasive measurements of respiratory phase angle offer a surrogate of disease severity in COPD? 2- Tidal breathing data
Authors: Irisz Levai, Kathryn Kimber, Willem de Boer, John Bier, Ravi Mahadeva, Joan Lasenby, Richard Iles
Journal: European Respiratory Journal (2013)

Introduction: During respiration, the thorax and abdomen change in volume. Increased resistance changes the phasing of these movements. Structured Light Plethysmography (SLP) is a non-invasive method of assessing the movement of thorax and abdominal wall. The movement of a projected grid of light records compartment volume change, from which a Konno-Mead loop (KM), phase angle (Phi) and entropy can be derived.  Aims: To interrogate Phi during Tidal breathing (TB) between COPD and controls.  Methods: TB data were collected from 10 COPD patients in exacerbation (av Age 71.8, (47-92) (No PFT), and 10 controls (Av Age 55, Av FEV1% 95 (95-105). 17 parameters were derived including Overall Phase (OPhi), principle angle (PA), KM spread, IT and ET. KM loop principal angle and spread was derived from Principal Component Analysis. For all parameters except OPhi, the mean, median and entropy (ApEn*) were calculated. The Mann Whitney and Brown-Forsythe tests were applied for significance.  Results: Mean Phi, Median Phi, ApEn, KM Spread, Mean Angle Change, Mean IT, Median IT, ApEn IT, and ApEn ET were statistically significant. For controls KM Spread, the ApEn Phi was low, suggesting regular TB. Entropy of IT and ET, was high in COPD.  Conclusion: SLP enables a non-invasive and objective assessment of the chaotic tidal breathing patterns in COPD.
Adolescents' use of purpose built shade in secondary schools: cluster randomised controlled trial
Authors: S. J Dobbinson, V. White, M. A Wakefield, K. M Jamsen, V. White, P. M Livingston, D. R English, J. A Simpson
Journal: BMJ (2009)

<b>Objective</b> To examine whether students use or avoid newly shaded areas created by shade sails installed at schools. <b>Design</b> Cluster randomised controlled trial with secondary schools as the unit of randomisation. <b>Setting</b> 51 secondary schools with limited available shade, in Australia, assessed over two spring and summer terms. <b>Participants</b> Students outside at lunch times. <b>Intervention</b> Purpose built shade sails were installed in winter 2005 at full sun study sites to increase available shade for students in the school grounds. <b>Main outcome measure</b> Mean number of students using the primary study sites during weekly observations at lunch time. <b>Results</b> Over the study period the mean change in students using the primary study site from pre-test to post-test was 2.63 (95% confidence interval 0.87 to 4.39) students in intervention schools and −0.03 (−1.16 to 1.09) students in control schools. The difference in mean change between groups was 2.67 (0.65 to 4.68) students (P=0.011). <b>Conclusions</b> Students used rather than avoided newly shaded areas provided by purpose built shade sails at secondary schools in this trial, suggesting a practical means of reducing adolescents' exposure to ultraviolet radiation. <b>Trial registration</b> Exempt.
Patterns of gas and liquid reflux during transient lower oesophageal sphincter relaxation: a study using intraluminal electrical impedance
Authors: D Sifrim, J Silny, R H Holloway, J J Janssens
Journal: Gut (1999)

Background Belching has been proposed as a major mechanism underlying acid gastro-oesophageal reflux in normal subjects. However, the presence of oesophageal gas has not been measured directly but only inferred from manometry. Aims To investigate, using intraluminal electrical impedance, the patterns of gas and liquid reflux during transient lower oesophageal sphincter (LOS) relaxations, the main mechanism of acid reflux in normal subjects. Methods Impedance changes associated with the passage of gas were studied in vitro, and in vivo in cats. Oesophageal manometry, pH, and intraluminal electrical impedance measurements were performed in 11 normal subjects after a meal. Results Gas reflux caused a sudden increase in impedance that propagated rapidly to the proximal oesophagus whereas liquid reflux induced a retrogressively propagated fall in impedance. Impedance showed gas or liquid reflux during most (102/141) transient LOS relaxations. When acid reflux occurred, impedance showed evidence of intraoesophageal retrograde flow of liquid in the majority (78%) of events. Evidence of gas retroflow was found in almost half (47%) of acid reflux episodes. When present together, however, liquid preceded gas on 44% of occasions. Overall, gas reflux occurred as the initial event in only 25% of acid reflux episodes. Conclusions These findings suggest that in upright normal subjects, although belching can precipitate acid reflux, most acid reflux occurs as a primary event.
Expression of Kinase Suppressor of Ras1 Enhances Cisplatin-Induced Extracellular Signal–Regulated Kinase Activation and Cisplatin Sensitivity
Authors: Min Kim, Ying Yan, Robert L. Kortum, Scott M. Stoeger, Magdalene K. Sgagias, Kwangmoon Lee, Robert E. Lewis, Kenneth H. Cowan
Journal: Cancer Research (2005)

Kinase suppressor of Ras1 (KSR1) interacts with several mitogen-activated protein (MAP) kinase pathway components, including Raf, MAP/extracellular signal-regulated kinase (ERK) kinase (MEK), and ERK, and acts as a positive regulator of the Ras signaling cascade. Previous studies have shown that exposure of cells to the anticancer agent cisplatin (cis-diamminedichloroplatinum, CDDP) is associated with changes in multiple signal transduction pathways, including c-Jun-NH2-kinase, ERK, and p38 pathways. Moreover, ERK activation has been linked to changes in cell survival following CDDP treatment. In this report, we have examined the effects of KSR1 expression on the sensitivity of cells to CDDP-induced apoptosis. Loss of KSR1 expression in mouse embryo fibroblasts (MEFs) derived from KSR1 knockout mice (KSR-/- MEF) is associated with decreased CDDP-induced ERK activation and increased resistance to CDDP-induced apoptosis compared with wild-type MEFs (KSR+/+ MEF). Furthermore, transduction of KSR-/- MEFs and MCF-7 breast cancer cells with wild-type KSR1 resulted in enhanced ERK activation following CDDP exposure and increased sensitivity to CDDP. In addition, inhibition of ERK activation by exposing MEFs to the MEK1/2-specific inhibitors PD98059 and U0126 protected both KSR+/+ and KSR-/- MEFs cells from CDDP-induced apoptosis. These results indicate that KSR1-mediated regulation of ERK activity represents a novel determinant of CDDP sensitivity of cancer cells.
Immunohistochemical Methods for Predicting Cell of Origin and Survival in Patients With Diffuse Large B-Cell Lymphoma Treated With Rituximab
Authors: Paul N. Meyer, Kai Fu, Timothy C. Greiner, Lynette M. Smith, Jan Delabie, Randy D. Gascoyne, German Ott, Andreas Rosenwald, Rita M. Braziel, Elias Campo, Julie M. Vose, Georg Lenz, Louis M. Staudt, Wing C. Chan, Dennis D. Weisenburger
Journal: Journal of Clinical Oncology (2010)

Patients with diffuse large B-cell lymphoma (DLBCL) can be divided into prognostic groups based on the cell of origin of the tumor as determined by microarray analysis. Various immunohistochemical algorithms have been developed to replicate these microarray results and/or stratify patients according to survival. This study compares some of those algorithms and also proposes some modifications.Two-hundred and sixty-two cases of de novo DLBCL treated with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like therapy were examined.The Choi algorithm and Hans algorithm had high concordance with the microarray results. Modifications of the Choi and Hans algorithms for ease of use still retained high concordance with the microarray results. Although the Nyman and Muris algorithms had high concordance with the microarray results, each had a low value for either sensitivity or specificity. The use of LMO2 alone showed the lowest concordance with the microarray results. A new algorithm (Tally) using a combination of antibodies, but without regard to the order of examination, showed the greatest concordance with microarray results. All of the algorithms divided patients into groups with significantly different overall and event-free survivals, but with different hazard ratios. With the exception of the Nyman algorithm, this survival prediction was independent of the International Prognostic Index. Although the Muris algorithm had prognostic significance, it misclassified a large number of cases with activated B-cell type DLBCL.The Tally algorithm showed the best concordance with the microarray data while maintaining prognostic significance and ease of use.
Authors’ response: single versus combination antibiotic therapy in adults hospitalised with community acquired pneumonia
Authors: C Rodrigo, W S Lim
Journal: Thorax (2013)

We thank van der Eerden et al 1 for their interest in our work2. We agree that pathogen-directed therapy (PDT) is desirable in adults with community-acquired pneumonia (CAP) admitted to hospital. In their report, the authors claim that microbiological investigations including sputum and pleural fluid …
L-Arginine deficiency causes airway hyperresponsiveness after the late asthmatic reaction
Authors: H. Maarsingh, B. E. Bossenga, I. S. T. Bos, H. H. Volders, J. Zaagsma, H. Meurs
Journal: European Respiratory Journal (2009)

Peroxynitrite has been shown to be crucially involved in airway hyperresponsiveness (AHR) after the late asthmatic reaction (LAR). Peroxynitrite production may result from simultaneous synthesis of nitric oxide (NO) and superoxide by inducible NO-synthase (iNOS) at low l-arginine concentrations. l-Arginine availability to iNOS is regulated by its cellular uptake, which can be inhibited by eosinophil-derived polycations and by arginase, which competes with iNOS for the common substrate. Using a guinea pig model of allergic asthma, we investigated whether aberrant l-arginine homeostasis could underlie peroxynitrite-mediated AHR after the LAR. After the LAR, arginase activity in the airways and eosinophil peroxidase release from bronchoalveolar lavage cells were increased. These changes were associated with a 2.0-fold AHR to methacholine as measured in isolated perfused tracheal preparations. AHR was reduced by exogenous l-arginine administration. Moreover, both the arginase inhibitor <i>N</i><sup>ω</sup>-hydroxy-nor-l-arginine (nor-NOHA) and the polycation antagonist heparin normalised airway responsiveness. These effects were reversed by the nitric oxide synthase inhibitor <i>N</i><sup>ω</sup>-nitro-l-arginine methyl ester (l-NAME), indicating that both agents reduced AHR by restoring bronchodilating NO production. In conclusion, in allergen-challenged guinea pigs, the AHR after the LAR is caused by arginase- and polycation-induced attenuation of l-arginine availability to iNOS, which may switch the enzyme to simultaneous production of superoxide and NO, and, consequently, peroxynitrite.
Prediction of Docetaxel Response in Human Breast Cancer by Gene Expression Profiling
Authors: Kyoko Iwao-Koizumi, Ryo Matoba, Noriko Ueno, Seung Jin Kim, Akiko Ando, Yasuo Miyoshi, Eisaku Maeda, Shinzaburo Noguchi, Kikuya Kato
Journal: Journal of Clinical Oncology (2005)

Docetaxel is one of the most effective anticancer drugs available in the treatment of breast cancer. Nearly half of the treated patients, however, do not respond to chemotherapy and suffer from side effects. The ability to reliably predict a patient's response based on tumor gene expression will improve therapeutic decision making and save patients from unnecessary side effects.A total of 44 breast tumor tissues were sampled by biopsy before treatment with docetaxel, and the response to therapy was clinically evaluated by the degree of reduction in tumor size. Gene expression profiling of the biopsy samples was performed with 2,453 genes using a high-throughput reverse transcriptase polymerase chain reaction technique. Using genes differentially expressed between responders and nonresponders, a diagnostic system based on the weighted-voting algorithm was constructed.This system predicted the clinical response of 26 previously unanalyzed samples with over 80% accuracy, a level promising for clinical applications. Diagnostic profiles in nonresponders were characterized by elevated expression of genes controlling the cellular redox environment (ie, redox genes, such as thioredoxin, glutathione-S-transferase, and peroxiredoxin). Overexpression of these genes protected cultured mammary tumor cells from docetaxel-induced cell death, suggesting that enhancement of the redox system plays a major role in docetaxel resistance.These results suggest that the clinical response to docetaxel can be predicted by gene expression patterns in biopsy samples. The results also suggest that one of the molecular mechanisms of the resistance is activation of a group of redox genes.
Radiological findings and correlation to clinical outcome in patients admitted due to influenza A (H1N1) infection
Authors: Beatriz Maria Jimenez Rodriguez, Rosa Lina De los Santos López, Julián Andrés Ceballos Gutierrez, Irene Jimenez Rodriguez, Bernardino Ancazar Navarrete, Rosa Maria Ortiz Comino
Journal: European Respiratory Journal (2013)

OBJECTIVES : To examine whether radiological and clinical variables of patients hospitalized with H1N1 influenza infection are associated with disease severity and help predicting prognosis. MATERIAL: A retrospective observational study, which included patients hospitalized for influenza AH1N1 confirmed infection during 2009-2010, 2010-2011.Multivariate analysis was performed looking for variables that predicted the primary outcome (ICU admission and / or death during hospitalization), showing the results of the confidence intervals at 95% for the OR. RESULTS : during the study periods 98 patients with confirmed Influenza AH1N1 infection were admitted to our hospital, 16.3% requiring ICU admission and total hospital mortality of 6.1%. Regarding the radiological characteristics at admission, 26.8% had a normal study, 38.8% bilateral infiltrates and 24.5% unilateral infiltrates. Patients who met the primary outcome differed by a higher percentage of males, pregnant, bilateral infiltrates on admission, worse SpO2 and a higher percentage of complicated disease. Multivariate analysis showed that the only variable that was significantly associated with the outcome was the SpO2 (p< 0,001), with a trend toward statistical significance for unilateral infiltrates.Although fewer patients were diagnosed in the period 2010-2011, their condition was more serious according to SpO2, and up to 44% required admission to the ICU, compared with only 5.6% in the patients diagnosed during 2010-2011. CONCLUSIONS : Influenza AH1N1 infection associated with ICU admission and/ or mortality during hospital admission may be determined by the degree of respiratory failure present at the ED.
Southwest Oncology Group S0802: A Randomized, Phase II Trial of Weekly Topotecan With and Without Ziv-Aflibercept in Patients With Platinum-Treated Small-Cell Lung Cancer
Authors: Jeffrey W. Allen, James Moon, Mary Redman, Shirish M. Gadgeel, Karen Kelly, Philip C. Mack, Hanna M. Saba, Mohamed K. Mohamed, Mohammad Jahanzeb, David R. Gandara
Journal: Journal of Clinical Oncology (2014)

Development of new therapies for previously treated small-cell lung cancer (SCLC) is a major unmet need. Here, we describe a randomized, phase II trial of weekly topotecan with or without ziv-aflibercept (VEGF-trap) in this clinical setting.
THE ROLE OF THE ANTERIOR PITUITARY IN THE CONTROL OF ALDOSTERONE SECRETION IN EXPERIMENTAL SECONDARY HYPERALDOSTERONISM*
Authors: James O. Davis, Nicholas A. Yankopoulos, Ferol Lieberman, John Holman, Robert C. Bahn
Journal: Journal of Clinical Investigation (1960)

1 The phrases "aldosterone secretion" or "hypersecretion of aldosterone" have been used to refer to actual meas- urements of the rate of secretion by the adrenal gland
Significance of systemic vascular resistance in determining the hemodynamic effects of hydralazine on large ventricular septal defects.
Authors: M Nakazawa, A Takao, Y Chon, T Shimizu, M Kanaya, K Momma
Journal: Circulation (1983)

The hemodynamic effects of hydralazine were studied in 17 infants and young children with ventricular septal defects to clarify the significance of systemic vascular resistance (SVR) in determining these effects. Patients with peak pulmonary arterial pressures greater than 75% of systemic pressure were placed in group I, which was further divided into group Ia (n = 6), consisting of those with a control SVR of 20 U.m2 or higher, and group Ib (n = 8), consisting of those with a lower SVR. Group II consisted of three patients with lower pulmonary arterial pressures. Intravenous injection of hydralazine (0.3 mg/kg) reduced SVR in all but two patients. The magnitude of reduction correlated with prehydralazine (control) SVR (r = .66, p less than .01). Systemic blood flow (Qs) increased from 3.7 +/- 0.7 to 5.0 +/- 0.8 l/min/m2 (p less than .005). The mean systemic arterial pressure for all patients decreased from 69 +/- 2 to 65 +/- 2 mm Hg (p less than .01) and the mean pulmonary arterial pressure decreased from the control value by 9 +/- 4% (p less than .01) in group I and by 17 +/- 1% in group II. Pulmonary blood flow (Qp) did not change significantly in either group. The Qp/Qs ratio was reduced from 3.6 +/- 0.4 to 2.4 +/- 0.2 (p less than .02) in group Ia. In sharp contrast, however, it increased from 2.6 +/- 0.3 to 3.3 +/- 0.5 (p = .06) in group Ib. The posthydralazine Qp/Qs ratio, expressed as percent of the control value, inversely correlated with the control SVR (r = -.61, p = .02) in group I. The response was not different in the group II patients. Thus, we conclude that control SVR is important for prediction of the hemodynamic effects of afterload reduction by hydralazine in infants and young children with large ventricular septal defects, and that this drug may be beneficial in patients with high control SVRs since a high SVR brings about a decrease in the Qp/Qs ratio.
Genetic Ancestry and Risk of Mortality among U.S. Latinas with Breast Cancer
Authors: Laura Fejerman, Donglei Hu, Scott Huntsman, Esther M. John, Mariana C. Stern, Christopher A. Haiman, Eliseo J. Pérez-Stable, Elad Ziv
Journal: Cancer Research (2013)

Multiple studies have reported that Latina women in the United States are diagnosed with breast cancer at more advanced stages and have poorer survival than non-Latina White women. However, Latinas are a heterogeneous group with individuals having different proportions of European, Indigenous American, and African genetic ancestry. In this study, we evaluated the association between genetic ancestry and survival after breast cancer diagnosis among 899 Latina women from the San Francisco Bay area. Genetic ancestry was estimated from single-nucleotide polymorphisms from an Affymetrix 6.0 array and we used Cox proportional hazards models to evaluate the association between genetic ancestry and breast cancer-specific mortality (tests were two-sided). Women were followed for an average of 9 years during which 75 died from breast cancer. Our results showed that Individuals with higher Indigenous American ancestry had increased risk of breast cancer-specific mortality [HR: 1.57 per 25% increase in Indigenous American ancestry; 95% confidence interval (CI): 1.08-2.29]. Adjustment for demographic factors, tumor characteristics, and some treatment information did not explain the observed association (HR: 1.75; 95%CI, 1.12-2.74). In an analysis in which ancestry was dichotomized, the hazard of mortality showed a two-fold increase when comparing women with less than 50% Indigenous American ancestry to women with 50% or more [HR, 1.89, 95%CI, 1.10-3.24]. This was also reflected by Kaplan-Meier survival estimates (P for log-rank test of 0.003). Overall, results suggest that genetic factors and/or unmeasured differences in treatment or access to care should be further explored to understand and reduce ethnic disparities in breast cancer outcomes.
Electrocardiogram of the Diving Seal
Authors: HERSCHEL V. MURDAUGH, JAMES C. SEABURY, WILLIAM L. MITCHELL
Journal: Circulation Research (1961)

During the normal dive, the seal has a reflex bradycardia that is not accompanied by inversion of P waves or T waves or by atrial or ventricular arrhythmias, although the seal does have an occasional block of conduction across the A-V node during normal diving. The reflex bradycardia during the dive appears to be mediated through vagal stimulus. The electrocardiograms of the seal during voluntary diving and during forced submersion with struggle are different.
Reproducibility of the Continuous Glucose Monitoring System Matches Previous Reports and the Intended Use of the Product
Authors: John J. Mastrototaro, Todd M. Gross
Journal: Diabetes Care (2003)

A recent article by Metzger et al. (1) questioned the reproducibility of the continuous glucose monitoring system (CGMS; Medtronic MiniMed). We were surprised by the authors’ conclusions, as their results were consistent with previously published reports. We believe the authors’ expectations for the CGMS did not coincide with its intended use. We were also puzzled by their use of a subjective assessment of clinical decision making when a validated tool, i.e., the Clarke error grid, is available (2). Finally, Metzger et al. dismissed the impact of an update to the CGMS software (Solutions 3.0) that does in fact improve the reproducibility evident in their data.

Although Metzger …
Controversies in epidemiology of occupational asthma
Authors: D. Gautrin, A.J. Newman-Taylor, H. Nordman, J-L. Malo
Journal: European Respiratory Journal (2003)

Epidemiology is the study of the distribution, determinants and outcome of disease. In this article, the recently acquired knowledge of the epidemiology of occupational asthma is described, as well as current areas of controversy. Incidence figures obtained from field studies in high-risk workplaces, medicolegal statistics and sentinel programmes indicate that approximately 10% of adult-onset asthma is attributable to the workplace. The strategy to identify cases through questionnaires and tools that address functional, immunological and physiopathological issues needs to be improved. Although few in number and limited to a handful of workplaces, cohort studies found that the risk of developing occupational asthma is determined less by individual susceptibility (e.g. atopy, tobacco smoking, human leukocyte antigen phenotype) and more by the level of exposure to its causes; in general, the higher the exposure, the greater the risk, and, by implication, lowering the level of exposure reduces the incidence of disease. Occupational asthma can be used as a satisfactory model for the development of adult-onset asthma. There is a great need to develop intervention strategies through adequate surveillance programmes in high-risk workplaces.
The G cells in pernicious anaemia
Authors: J. M. Polak, I. Coulling, W. Doe, A. G. E. Pearse
Journal: Gut (1971)

An indirect immunofluorescence technique, using the globulin fraction of rabbit antihuman gastrin serum, was applied to formalin-fixed material obtained by suction biopsy from the fundic mucosa of nine cases of pernicious anaemia. Cytochemical tests for endocrine polypeptide cells of the APUD series, in which the G cell is included, were carried out in parallel with immunofluorescence and with ultrastructural observations. G cells were present, in large numbers, in five of the nine cases studied. In the remaining four cases the predominantly intestinalized glands contained only enterochromaffin in cells. Because of their low gastrin content (immunofluorescence), low secretion granule content (cytochemistry), and the associated ultrastructural findings, it is suggested that the G cells of the fundic mucosa are in a state of high synthetic and high secretory activity.