tbuckley/cabot-search huggingface dataset:
Arm activity in daily life in chronic obstructive pulmonary disease (COPD)
Authors: Tania Janaudis-Ferreira, Sunita Mathur, Julia Romano, Roger Goldstein, Dina Brooks
Journal: European Respiratory Journal (2014)

Rationale : To date, no study has objectively compared arm activity in daily life in individuals with COPD with healthy controls. Our objectives were to determine whether individuals with COPD have decreased arm activity during daily life compared to healthy controls and to investigate the relationships between arm activity during daily life and dyspnea during activities of daily living (ADL), arm exercise capacity and self-reported performance during ADL.  Methods:  Participants worn an actigraph on the dominant arm for 24 hours, 7 consecutive days. Corrections for walking time were made and mean activity scores (counts/epoch) per day were averaged over the 7 days and presented as daily arm activity.Dyspnea during ADL, arm exercise capacity and self-reported performance during ADL were measured using the dyspnea domain of the Chronic Respiratory Disease Questionnaire (CRQ dyspnea ), the Unsupported Upper Limb Exercise test (UULEX) and the Canadian Occupational Performance Measure (COPM).  Results:  Thirty individuals with COPD (FEV 1 % = 33 ± 18%; 70 ± 7 yrs) and 14 healthy controls (FEV 1 % = 104 ± 16%; 66 ± 9 yrs) exhibited similar daily arm activity (138 ± 31;COPD vs. 133 ± 21; controls) (p = 0.6). Arm exercise capacity was decreased in patients with COPD (513 ± 132 (COPD) vs. 751 ± 144 (controls)). Weak correlations were found between daily arm activity and CRQ dyspnea , arm exercise capacity and self-reported performance during ADL, ranging from -0.22 to 0.13 (p ≥ 0.2).  Conclusions:  Individuals with COPD have similar arm activity levels than health elderly controls despite decreased arm exercise capacity.
Platelet count/spleen diameter ratio: proposal and validation of a non-invasive parameter to predict the presence of oesophageal varices in patients with liver cirrhosis
Authors: E Giannini, F Botta, P Borro, D Risso, P Romagnoli, A Fasoli, M R Mele, E Testa, C Mansi, V Savarino, R Testa
Journal: Gut (2003)

Cirrhotic patients frequently undergo screening endoscopy for the presence of oesophageal varices (OV). In the future, this social and medical burden will increase due to the greater number of patients with chronic liver disease and their improved survival. In this study, our aims were (1) to identify clinical, biochemical, and ultrasonographic parameters which might non-invasively predict the presence of OV in patients with liver cirrhosis; (2) to evaluate the reproducibility of the obtained results in a different, although related, further group of patients; and (3) to assess the predictiveness of the identified rules in patients with compensated cirrhosis.In the first part of the study we retrospectively evaluated the presence of OV in 145 cirrhotic patients, and in the second part we evaluated the reproducibility of the study results in a subsequent group of 121 patients. Finally, we evaluated these parameters in a subgroup of 145 patients with compensated disease. All 266 patients underwent a complete biochemical workup, upper digestive endoscopy, and ultrasonographic measurement of spleen bipolar diameter. Platelet count/spleen diameter ratio was calculated for all patients.The prevalence rates of OV were 61% and 58% in the first and second groups of patients, respectively. In the first part of the study, we found that platelet count, spleen diameter, platelet count/spleen diameter ratio, and Child- Pugh class were significantly different among patients with or without OV, although the platelet count/spleen diameter ratio was the only parameter which was independently associated with the presence of OV in a multivariate analysis. A platelet count/spleen diameter ratio cut off value of 909 had 100% negative predictive value for a diagnosis of OV. This result was reproduced in the second group of patients as well as in patients with compensated disease. In a cost-benefit analysis, screening cirrhotic patients according to the "platelet count/spleen diameter ratio strategy" was far more cost effective compared with the "scope all strategy".The platelet count/spleen diameter ratio is the only parameter which is independently associated with the presence of OV, and its negative predictive value is reproducible. Its use is of value even in the subgroup of patients with compensated disease, and it is also cost effective.
Letrozole Is More Effective Neoadjuvant Endocrine Therapy Than Tamoxifen for ErbB-1– and/or ErbB-2–Positive, Estrogen Receptor–Positive Primary Breast Cancer: Evidence From a Phase III Randomized Trial
Authors: Matthew J. Ellis, Andrew Coop, Baljit Singh, Louis Mauriac, Antonio Llombert-Cussac, Fritz Jänicke, William R. Miller, Dean B. Evans, Margaret Dugan, Carolyn Brady, Erhard Quebe-Fehling, Mieke Borgs
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Expression of ErbB-1 and ErbB-2 (epidermal growth factor receptor and HER2/neu) in breast cancer may cause tamoxifen resistance, but not all studies concur. Additionally, the relationship between ErbB-1 and ErbB-2 expression and response to selective aromatase inhibitors is unknown. A neoadjuvant study for primary breast cancer that randomized treatment between letrozole and tamoxifen provided a context within which these issues could be addressed prospectively. PATIENTS AND METHODS: Postmenopausal patients with estrogen– and/or progesterone receptor–positive (ER+ and/or PgR+) primary breast cancer ineligible for breast-conserving surgery were randomly assigned to 4 months of neoadjuvant letrozole 2.5 mg daily or tamoxifen 20 mg daily in a double-blinded study. Immunohistochemistry (IHC) for ER and PgR was conducted on pretreatment biopsies and assessed by the Allred score. ErbB-1 and ErbB-2 IHC were assessed by intensity and completeness of membranous staining according to published criteria. RESULTS: For study biopsy-confirmed ER+ and/or PgR+ cases that received letrozole, 60% responded and 48% underwent successful breast-conserving surgery. The response to tamoxifen was inferior (41%, P = .004), and fewer patients underwent breast conservation (36%, P = .036). Differences in response rates between letrozole and tamoxifen were most marked for tumors that were positive for ErbB-1 and/or ErbB-2 and ER (88% v 21%, P = .0004). CONCLUSION: ER+, ErbB-1+, and/or ErbB-2+ primary breast cancer responded well to letrozole, but responses to tamoxifen were infrequent. This suggests that ErbB-1 and ErbB-2 signaling through ER is ligand-dependent and that the growth-promoting effects of these receptor tyrosine kinases on ER+ breast cancer can be inhibited by potent estrogen deprivation therapy.
Hypoxia-induced pulmonary hypertension: comparison of soluble epoxide hydrolase deletion vs. inhibition
Authors: Benjamin Keserü, Eduardo Barbosa-Sicard, Ralph T. Schermuly, Hiromasa Tanaka, Bruce D. Hammock, Norbert Weissmann, Beate Fisslthaler, Ingrid Fleming
Journal: Cardiovascular Research (2009)

The C-terminal domain of the soluble epoxide hydrolase (sEH) metabolizes epoxyeicosatrienoic acids (EETs) to their less active diols, while the N-terminal domain demonstrates lipid phosphatase activity. As EETs are potent vasoconstrictors in the pulmonary circulation, we assessed the development of pulmonary hypertension induced by exposure to hypoxia (10% O2) for 21 days in wild-type (WT) and sEH−/− mice and compared the effects with chronic (4 months) sEH inhibition. In isolated lungs from WT mice, acute hypoxic vasoconstriction (HPV) was potentiated by sEH inhibition and attenuated by an EET antagonist. After prolonged hypoxia, the acute HPV and sensitivity to the EET antagonist were increased, but potentiation of vasoconstriction following sEH inhibition was not evident. Chronic hypoxia also stimulated the muscularization of pulmonary arteries and decreased sEH expression in WT mice. In normoxic sEH−/− mice, acute HPV and small artery muscularization were greater than that in WT lungs and enhanced muscularization was accompanied with decreased voluntary exercise capacity. Acute HPV in sEH−/− mice was insensitive to sEH inhibition but inhibited by the EET antagonist and chronic hypoxia induced an exaggerated pulmonary vascular remodelling. In WT mice, chronic sEH inhibition increased serum EET levels but failed to affect acute HPV, right ventricle weight, pulmonary artery muscularization, or voluntary running distance. In human donor lungs, the sEH was expressed in the wall of pulmonary arteries, however, sEH expression was absent in samples from patients with pulmonary hypertension. These data suggest that a decrease in sEH expression is intimately linked to pathophysiology of hypoxia-induced pulmonary remodelling and hypertension. However, as sEH inhibitors do not promote the development of pulmonary hypertension it seems likely that the N-terminal lipid phosphatase may play a role in the development of this disease.
Risk of severe liver disease in nonalcoholic fatty liver disease with normal aminotransferase levels: A role for insulin resistance and diabetes
Authors: Anna Ludovica Fracanzani, Luca Valenti, Elisabetta Bugianesi, Marco Andreoletti, Agostino Colli, Ester Vanni, Cristina Bertelli, Erika Fatta, Daniela Bignamini, Giulio Marchesini, Silvia Fargion
Journal: Hepatology (2008)

Abstract It is uncertain whether patients with nonalcoholic fatty liver disease (NAFLD) and normal alanine aminotransferase (ALT) have a milder disease and should undergo liver biopsy. We reviewed the histological data of 458 Italian patients with NAFLD in whom liver biopsy was indicated by altered liver enzymes (395 cases, 86%), or persistently elevated ferritin or long-lasting severe steatosis (63 cases). Factors associated with nonalcoholic steatohepatitis (NASH) and fibrosis ≥ 2 were identified by multivariate analysis. Patients with normal ALT were significantly older, had lower body mass index, fasting triglycerides, insulin resistance according to homeostasis model assessment (HOMA-IR), ALT, and gamma-glutamyltransferase, but a higher prevalence of hypertension. NASH was diagnosed in 59% and 74% of the patients with normal and increased ALT, respectively ( P = 0.01). In the overall series of patients, NASH was independently predicted by ALT (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.04–1.19 per 10-IU/mL increase) and diabetes (OR, 1.5; 95% CI, 1.1–2.0). The same variables were selected in patients with increased ALT, whereas in those with normal ALT, HOMA-IR and ALT were independent predictors. Severe fibrosis was independently predicted by serum ferritin (OR, 1.04; 95% CI, 1.001–1.08 per 50-ng/mL increase), ALT (OR, 1.07; 95% CI, 1.02–1.14), and diabetes (OR, 1.8; 95% CI, 1.4–2.3) in the overall series, serum ferritin and diabetes in those with increased ALT, and only HOMA-IR (OR, 1.97; 95% CI, 1.2–3.7) in patients with normal ALT. Conclusion: Normal ALT is not a valuable criterion to exclude patients from liver biopsy. Alterations in glucose metabolism and insulin resistance in subjects with normal ALT should also be considered in the selection of NAFLD cases for histological assessment of disease severity and progression. (Hepatology 2008.)
Small GTPase RhoE/Rnd3 Is a Critical Regulator of Notch1 Signaling
Authors: Zehua Zhu, Kristina Todorova, Kevin K. Lee, Jun Wang, Eunjeong Kwon, Ivan Kehayov, Hyung-Gu Kim, Vihren Kolev, G. Paolo Dotto, Sam W. Lee, Anna Mandinova
Journal: Cancer Research (2014)

Aberrations of Notch signaling have been implicated in a variety of human cancers. Oncogenic mutations in NOTCH1 are common in human T-cell leukemia and lymphomas. However, loss-of-function somatic mutations in NOTCH1 arising in solid tumors imply a tumor suppressor function, which highlights the need to understand Notch signaling more completely. Here, we describe the small GTPase RhoE/Rnd3 as a downstream mediator of Notch signaling in squamous cell carcinomas (SCC) that arise in skin epithelia. RhoE is a transcriptional target of activated Notch1, which is attenuated broadly in SCC cells. RhoE depletion suppresses Notch1-mediated signaling in vitro, rendering primary keratinocytes resistant to Notch1-mediated differentiation and thereby favoring a proliferative cell fate. Mechanistic investigations indicated that RhoE controls a key step in Notch1 signaling by mediating nuclear translocation of the activated portion of Notch1 (N1IC) through interaction with importins. Our results define RhoE as a Notch1 target that is essential for recruitment of N1IC to the promoters of Notch1 target genes, establishing a regulatory feedback loop in Notch1 signaling. This molecular circuitry may inform distinct cell fate decisions to Notch1 in epithelial tissues, where carcinomas such as SCC arise.
Assessment of disability with the World Health Organisation Disability Assessment Schedule II in patients with ankylosing spondylitis
Authors: A van Tubergen
Journal: Annals of the Rheumatic Diseases (2003)

<b>Objective:</b> To investigate in ankylosing spondylitis (AS) whether the newly developed World Health Organisation Disability Assessment Schedule II (WHODAS II) is a useful instrument for measuring disability, to assess its responsiveness in relation to other traditional disease specific instruments, and to identify factors that are associated with both short term and long term scores on the WHODAS II. <b>Methods:</b> Patients with AS from a randomised controlled trial assessing the efficacy of spa treatment (n=117) and from a five year longitudinal observational study (n=97) participated. The patients completed several questionnaires, including the WHODAS II. After a three week course of spa treatment, 31 patients again completed all questionnaires to assess responsiveness. To determine to what degree the WHODAS II reflects some AS oriented measures on disease activity, functioning, and quality of life, correlation coefficients between the WHODAS II and these other questionnaires were calculated. Responsiveness was calculated by the effect size (ES) and standardised response mean (SRM). Linear regression analysis was performed to explore which factors might be associated with short term changes on the WHODAS II and to investigate (in the observational study) which factors of WHODAS II might predict disability five years later. <b>Results:</b> Mean score on the WHODAS II was 23.9 (SD 15.5 (range 0.0−76.1)). Scores on the WHODAS II were significantly correlated with all disease specific questionnaires measured (all p&lt;0.001). The WHODAS II showed a comparable short term responsiveness score (SRM 0.41; ES 0.39). In regression analysis these short term changes on the WHODAS II were significantly associated with changes in functioning (β coefficient 4.25, 95% confidence interval (95% CI) 1.24 to 7.26, p=0.007). In the observational study, disease activity (β coefficient 0.35, 95% CI 0.17 to 0.53, p&lt;0.000) as well as functioning (β coefficient 0.23, 95% CI 0.09 to 0.38, p=0.002) seemed to significantly predict disability (WHODAS II) after five years. <b>Conclusion:</b> The WHODAS II is a useful instrument for measuring disability in AS in that it accurately reflects disease specific instruments and that it shows similar responsiveness scores. In AS, a short term change on the WHODAS II is associated with a change in physical function. At the group level, disease activity and physical functioning may predict disability after five years.
Gastrointestinal symptoms in the irritable bowel compared with peptic ulcer and inflammatory bowel disease.
Authors: W G Thompson
Journal: Gut (1984)

Symptoms of 50 patients with the irritable bowel syndrome were compared with those of 49 with endoscopically proven peptic ulcer disease and 49 with radiologically or endoscopically proven inflammatory bowel disease using a questionnaire which was administered after the diagnosis was made. Symptoms of bowel dysfunction including pain related to bowel movements were more likely to occur in the irritable bowel syndrome than peptic ulcer disease. Only abdominal distension, straining at stool and scybala, however, were significantly more likely in the irritable bowel syndrome than inflammatory bowel disease. Four symptoms previously shown to be more common in irritable bowel syndrome than in organic abdominal disease were combined. The more of these symptoms that were present, the more likely were the patients to have the irritable bowel syndrome than peptic ulcer disease. Symptoms of gut dysfunction are highly discriminating between irritable bowel syndrome and peptic ulcer disease but less so between irritable bowel syndrome and inflammatory bowel disease.
Inhibition of neutrophil oxidant secretion by D-penicillamine: scavenging of H2O2 and HOCl.
Authors: M J Ledson, R C Bucknall, S W Edwards
Journal: Annals of the Rheumatic Diseases (1992)

D-Penicillamine inhibited oxidant secretion from human neutrophils after activation by the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMet-Leu-Phe), as assessed by luminol dependent chemiluminescence. In contrast, this drug had little effect on either intracellular oxidant production or lucigenin dependent chemiluminescence activated by the same agonist. The drug was shown to scavenge both H2O2 and HOCl in a cell free luminol chemiluminescence system, though its ability to scavenge HOCl was greater than that for H2O2. Both these oxidants could oxidise the drug, but again HOCl was more potent than H2O2. When D-penicillamine was oxidised by exposure to H2O2 it could no longer serve as a scavenger of secreted oxidants from neutrophils. These data suggest that in vivo the preferential scavenging of HOCl may be important under pathological conditions where secreted myeloperoxidase may be functional.
International expert opinion on the management of infection caused by azole-resistant Aspergillus fumigatus
Authors: Paul E. Verweij, Michelle Ananda-Rajah, David Andes, Maiken C. Arendrup, Roger J. Brüggemann, Anuradha Chowdhary, Oliver A. Cornely, David W. Denning, Andreas H. Groll, Koichi Izumikawa, Bart Jan Kullberg, Katrien Lagrou, Johan Maertens, Jacques F. Meis, Pippa Newton, Iain Page, Seyedmojtaba Seyedmousavi, Donald C. Sheppard, Claudio Viscoli, Adilia Warris, J. Peter Donnelly
Journal: Drug Resistance Updates (2015)

An international expert panel was convened to deliberate the management of azole-resistant aspergillosis. In culture-positive cases, in vitro susceptibility testing should always be performed if antifungal therapy is intended. Different patterns of resistance are seen, with multi-azole and pan-azole resistance more common than resistance to a single triazole. In confirmed invasive pulmonary aspergillosis due to an azole-resistant Aspergillus, the experts recommended a switch from voriconazole to liposomal amphotericin B (L-AmB; Ambisome(®)). In regions with environmental resistance rates of ≥10%, a voriconazole-echinocandin combination or L-AmB were favoured as initial therapy. All experts recommended L-AmB as core therapy for central nervous system aspergillosis suspected to be due to an azole-resistant Aspergillus, and considered the addition of a second agent with the majority favouring flucytosine. Intravenous therapy with either micafungin or L-AmB given as either intermittent or continuous therapy was recommended for chronic pulmonary aspergillosis due to a pan-azole-resistant Aspergillus. Local and national surveillance with identification of clinical and environmental resistance patterns, rapid diagnostics, better quality clinical outcome data, and a greater understanding of the factors driving or minimising environmental resistance are areas where research is urgently needed, as well as the development of new oral agents outside the azole drug class.
Fl-160. A surface antigen of Trypanosoma cruzi that mimics mammalian nervous tissue.
Authors: W C Van Voorhis, H Eisen
Journal: The Journal of Experimental Medicine (1989)

Chagas' disease, caused by Trypanosoma cruzi, is an excellent model for autoimmune disease induced by an infectious agent. Transfer of T cells, directed against crossreactive antigens of T. cruzi and nervous tissue, have been shown to reproduce pathology found in chronic Chagas' disease. We used recombinant DNA technology to characterize one of these crossreactive antigens (Fl-160). We have cloned DNA from T. cruzi, which expresses a protein corresponding to a 160-kD protein found on the surface of the trypanosome, overlying the flagellum. This clone hybridizes to a 4.5-kb poly(A)+ RNA that is distributed in a differentiation-specific manner, suggesting expression of this protein is transcriptionally controlled. Antibodies to this protein crossreact with a 48-kD mammalian nervous tissue protein found in sciatic nerve, brain, and myenteric plexi of gut. The myenteric plexi are destroyed by inflammatory infiltrates in Chagas' disease, leading to the characteristic megaesophagus and megacolon Chagas' disease pathology. Thus, this antigen is a candidate antigen for autoimmune mimicry leading to nervous tissue pathology.
Nephritis in Textile Workers
Authors: R. Platt
Journal: BMJ (1947)

Personal observation of a woman suffering from diabetes insipidus over a period of 26 years has enabled me to ascertain the complete adaptation of such a patient to a normal life when the lesion is not fatal.It has also enabled me to study one more case of uterine atony undoubtedly related to hypothalamic- posterior-pituitary insufficiency.
Air temperature and physiological and subjective responses during competitive singles tennis
Authors: Sarah M Morante, John R Brotherhood
Journal: British Journal of Sports Medicine (2007)

Objectives: This report describes the thermal stresses and strains during competitive singles tennis. Methods: Thermoregulatory responses were investigated during best of three set tennis matches among 25 players. A total of 86 observations were made from 43 matches played, covering each season, with ambient temperatures ranging from 14.5 to 38.4°C. Core body temperature and skin temperature were recorded each minute throughout the match, whilst heart rate was logged every 15 s. Body mass and fluid intake were measured before the match, after 30 min of play and at the completion of the match to determine sweat rate. Subjective ratings of thermal strain included thermal comfort, sweatiness and perceived exertion. The thermal environment was assessed by dry bulb, wet bulb and natural wet bulb temperatures, globe temperature and wind speed. Results: Mean (SD) core temperature after 30 min of play was 38.4°C (0.4°C), and demonstrated no association with air temperature or wet bulb globe temperature. Mean skin temperature was 31.8°C (2.3°C) ranging from 25.7 to 36.5°C, and showed a positive association with air temperature (p&lt;0.001). Heart rate varied widely during play, resulting in a mean (SD) response of 136.1 (13.7) beats/min and no association with air temperature. Sweat rate averaged 1.0 (0.4) litres/h (0.2–2.4 litres/h) or 12.8 (5.5) ml/kg/h (2.7–26.0 ml/kg/h), and demonstrated a positive relationship with air temperature (p&lt;0.001). All subjective responses showed positive correlations with air temperature (p&lt;0.001). Conclusions: Stressful environmental conditions produce a high skin temperature and rating of thermal discomfort. However, overall thermoregulatory strain during tennis is moderate, with core temperature remaining within safe levels.