tbuckley/cabot-search huggingface dataset:
Short- and long-term effects of a physical activity counselling program in COPD
Authors: Wytske Altenburg, Johan Wempe, Mathieu de Greef, Nick ten Hacken, Huib Kerstjens
Journal: European Respiratory Journal (2014)

Background: Physical activity (PA) counseling might be an alternative for or complementary to pulmonary rehabilitation (PR). In this study, short- and long term effects of a PA counseling program were investigated in COPD patients from three settings: general practice, outpatient clinic and PR. In the PR subgroup counseling was added to a PR program.

Methods: In this randomized controlled trial 155 COPD patients, 102 males, median (IQR) age 62 (54-69) years, FEV1 60 (40-75) %pred were assigned to a 12-week PA counseling program or usual care. PA (pedometer (Yamax SW-200) and metabolic equivalents), exercise capacity (six-minute walking distance) and quality of life (Chronic Respiratory Questionnaire) were assessed at baseline, after three and 15 months.

Results: A significant difference between the counseling and usual care group in daily steps (803 steps, p=0.001) and daily PA (2214 steps+equivalents, p=0.001)) from 0-3 months was found in the total group, as well as in the outpatient subgroup (1816 steps, 2616 steps+equivalents, both p=0.007) and the PR subgroup (758 steps, 2151 steps+equivalents, both p=0.03). From 0-15 months no differences were found in PA neither in the total group nor in the subgroups. When patients with baseline PA>10000 steps (n=8), who can be considered as sufficiently active, were excluded, there was a significant long term effect of the counseling program on daily PA in the total group (p=0.017). Differences in exercise capacity and quality of life were only shown from 0-3 months in the outpatient subgroup.

Conclusion : Our PA counseling program effectively enhances PA level in COPD patients after three months. Inactive patients at baseline still benefit after 15 months.
Gene expression profiles that correlate with histologic grade in squamous cell carcinoma of the aerodigestive tract
Authors: Alexander Baras, Michael Filtz, Boram Kim, Christopher Moskaluk
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

1839 

Squamous cell carcinoma (SCC) is the most common cancer induced by tobacco use in the aerodigestive tract (head and neck region, tracheobronchial tree, and esophagus). A range of histologic differentiation exists in SCC, characterized as tumor grade, and is based on the recapitulation of the cellular stratification of squamous mucosa and the degree of keratinization, with higher grades correlating to more aggressive clinical behavior. As a first step to characterize the molecular basis of histologic grade in SCC, we performed gene expression profiling using Affymetrix U133A GeneChip on 87 cases of aerodigestive SCC. To access differential expression across grade we screened out genes not called significantly present in at least one class of grade. We next applied a non-parametric test (Kruskal-Wallis), with false discovery rate correction of 10%, to select genes with at least one significant difference across grade. This analysis resulted in 999 genes showing expression levels that were significantly correlated to differences in histologic grade in our cohort. Among these, we identified Sox4 (Sry-related HMG box 4), which is a transcription factor whose expression has been shown to correlate with malignant transformation in a variety of human tumors, including lung cancers, adenoid cystic carcinomas, and many others. Well differentiated (grade 1) SCCs express Sox4 at levels comparable to normal tissue, while higher grade cancers (2-4) progressively express higher levels of Sox4. We have confirmed this pattern in our cohort by quantitative RT-PCR. Rox1, the yeast homolog of Sox4 has been shown to down regulate the transcription of genes expressed in hypoxic conditions. From Sox4 RNAi knockdown data in a cell line system of a related head and neck tumor (adenoid cystic carcinoma), BNIP3, a pro-apoptotic factor, is up-regulated when Sox4 expression is decreased. Interestingly, BNIP3 is known to be up-regulated by HIF1a, a transcription factor whose activity is increased in hypoxic conditions and is known to be increased in SCC. We hypothesize that Sox4 over-expression in SCC may serve to counteract the transcriptional activation of BNIP3 by HIF1a. Our microarray data is supportive of this hypothesis. 

![Figure][1]  [1]: pending:yes
A systematic analysis of genetic dilated cardiomyopathy reveals numerous ubiquitously expressed and muscle‐specific genes
Authors: Magdalena Harakalova, Gijs Kummeling, Arjan Sammani, Marijke Linschoten, Annette F. Baas, Jasper van der Smagt, Pieter A. Doevendans, J. Peter van Tintelen, Dennis Dooijes, Michal Mokry, Folkert W. Asselbergs
Journal: European Journal of Heart Failure (2015)
Association among sleep apnea and pulmonary hypertension in highlanders
Authors: Tsogyal D. Latshang, Michael Furian, Sayaka Aeschbacher, Silvia Ulrich, Aizat K. Myrzaakmatova, Batyr Osmonov, Erkin M. Mirrakhimov, Talant Sooronbaev, Almaz Aldashev, Konrad E. Bloch
Journal: European Respiratory Journal (2013)

Background  The factors predisposing to high altitude pulmonary hypertension (HAPH), a form of PH occurring in high altitude residents, have not been well defined. We evaluated the association of sleep apnea and HAPH in highlanders.   Methods  In residents of the Aksay area, Kyrgyzstan, at 3250 m, we performed clinical examinations, echocardiography, polysomnography and arterial blood gas analyses. Data from highlanders with HAPH (mean pulmonary artery pressure by echocardiography mPAP >30 mmHg, in the absence of excessive erythrocytosis, heart or lung disease) were compared to those of healthy highlanders.   Results  Of 90 participants, 36 had HAPH (mPAP range 31-42 mmHg), 54 were healthy controls (mPAP range 13-28 mmHg, P 3%) due to sleep apnea (40±26 events/h), and a higher body mass index (28.7±4.7 kg/m2) compared to highlanders without HAPH (age 39±10y, nocturnal oxygen saturation 90±3%, ODI 19±14/h, body mass index 24.0±3.9 kg/m2, P   Conclusions  HAPH is associated with sleep apnea, older age and higher weight. Combined intermittent and chronic hypoxia due to sleep apnea and residence at high altitude may predispose to pulmonary hypertension.  Grants: OPO Foundation and Zurich Lung League.
Abstract 14375: Racial and Socio-Economic Differences in the Selection for Advanced Heart Failure Therapies
Authors: Neelima Nadella, Sevan Karadolian, Mohamed Ahmed, Celeste Williams, Henry E Kim
Journal: Circulation (2011)

BACKGROUND: Advanced heart failure therapies (AHFT) such as Ventricular Assist Devices and transplant prolong survival and improve quality of life. Few studies exist investigating the clinical and ...
Type 2 innate lymphoid cell counts are increased in patients with systemic sclerosis and correlate with the extent of fibrosis
Authors: Thomas Wohlfahrt, Svetlana Usherenko, Matthias Englbrecht, Clara Dees, Stefanie Weber, Christian Beyer, Kolja Gelse, Oliver Distler, Georg Schett, Jörg H W Distler, Andreas Ramming
Journal: Annals of the Rheumatic Diseases (2015)

Objective Type 2 innate lymphoid cells (ILC2s), a recently identified population of lymphoid cells lacking lineage-specific receptors, promote type 2 immunity and tissue remodelling. However, the contributive role of ILC2s in the pathogenesis of systemic sclerosis (SSc) is unknown. We aimed to evaluate the levels and correlations with fibrotic manifestations in SSc. Methods 69 patients with SSc and 47 healthy controls were included. Blood samples and skin sections were analysed by flow cytometry and immunohistochemically by staining two complementary panels of markers. Results Dermal and circulating ILC2s were significantly elevated in patients with SSc compared with controls. Dermal, but not circulating ILC2s were activated. Stratification of the SSc population in patients with limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) demonstrated increased levels of ILC2s in both subgroups with significantly higher frequencies in dcSSc compared with lcSSc. Moreover, dermal and circulating ILC2 counts correlated closely with the modified Rodnan skin score and with the presence of pulmonary fibrosis. Conclusions ILC2 counts are elevated in patients with SSc and correlate with the extent of skin fibrosis and the presence of interstitial lung disease providing compelling evidence for profibrotic effect of ILC2s in SSc.
The S-stamp in Descemet Membrane Endothelial Keratoplasty Safely Eliminates Upside-down Graft Implantation
Authors: Peter B. Veldman, Philip K. Dye, Jeffrey D. Holiman, Zachary M. Mayko, Christopher S. Sáles, Michael D. Straiko, Joshua D. Galloway, Mark A. Terry
Journal: Ophthalmology (2015)
Renin-Angiotensin System Inhibition in Conscious Dogs during Acute Hypoxemia
Authors: Chang-Seng Liang, Haralambos Gavras
Journal: Journal of Clinical Investigation (1978)

The role of the renin-angiotensin system in mediating the circulatory and metabolic responses to hypoxia was studied in three groups of conscious dogs that were infused continuously with normal saline, teprotide (10 μg/kg per min), and saralasin (1 μg/kg per min), respectively. Hypoxia was produced by switching from breathing room air to 5 or 8% oxygen-nitrogen mixture. Plasma renin activity increased from 2.3±0.4 to 4.9±0.8 ng/ml per h during 8% oxygen breathing, and from 2.8±0.4 to 8.4±1.8 ng/ml per h during 5% oxygen breathing. As expected, cardiac output, heart rate, mean aortic blood pressure, and left ventricular dP/dt and dP/dt/P increased during both 5 and 8% oxygen breathing in the saline-treated dogs; greater increases occurred during the more severe hypoxia. Teprotide and saralasin infusion diminished the hemodynamic responses to 5% oxygen breathing, but did not affect the responses to 8% oxygen breathing significantly. In addition, the increased blood flows to the myocardium, kidneys, adrenals, brain, intercostal muscle, and diaphragm that usually occur during 5% oxygen breathing were reduced by both agents. These agents also reduced the increases in plasma norepinephrine concentration during 5% oxygen breathing, but had no effects on tissue aerobic or anaerobic metabolism.
Abstract 6083: Sex Differences in 1-Year Mortality Following Acute Coronary Syndromes
Authors: Jeffrey S Berger, Laine E Elliott, L. Kristin Newby, Matthew Roe, Christopher B Granger, Paul W Armstrong, R. John Simes, Harvey D White, Frans Van de Werf, Judith S Hochman, Eric J Topol, Robert A Harrington, Robert M Califf, Pamela S Douglas
Journal: Circulation (2008)

Background : There is conflicting information whether sex modulates mortality following acute coronary syndromes (ACS). We investigated the relationships between sex, other clinical characteristics and 1-year mortality across the spectrum of ACS using a large database. Methods : Data from 6 ACS trials encompassing 1993 to 2006 were pooled. Of 81,010 patients, 21,409 (26%) were women. The ACS spectrum included 57,113 (24% women) STEMI, 13,376 (29% women) NSTEMI and 10,523 (39% women) unstable angina (UA). We compared 1-year mortality of women versus men in those surviving at least 30 days post ACS after multivariable adjustment using previously validated STEMI and NSTEMI/UA mortality models and coronary anatomy, Results : In the combined ACS population, women had higher unadjusted risk (HR 1.26, 95% CI 1.16 –1.36) compared with men. A significant interaction between sex and type of ACS was detected (P&lt;0.001). Women had an increased unadjusted 1-year mortality risk in STEMI (HR 1.43, 95% CI 1.30 –1.58) and NSTEMI (HR 1.17, 95% CI 0.98 –1.39) but a decreased risk in UA (HR 0.84, 95% CI 0.69 –1.02) compared with men. After adjustment for baseline characteristics (age, heart rate, systolic blood pressure, weight, race, Killip class, smoking status, and history of diabetes, heart failure, myocardial infarction or bypass surgery) women had a lower risk of 1-year mortality for each type of ACS (STEMI, HR 0.86, 95% CI 0.77– 0.96; NSTEMI, HR 0.81, 95% CI 0.67– 0.97; and UA, HR 0.65, 95% CI 0.53– 0.79). After further adjustment for in-hospital procedures and coronary anatomy, hazard ratios were unchanged and mortality at 1-year remained lower for women in all ACS types. Conclusions : Sex-based differences exist in unadjusted 1-year mortality following ACS and vary by type of clinical syndrome. Adjustment for baseline differences, in-hospital procedures and coronary anatomy reveal that women are actually at lower risk for 1-year mortality compared with men across the spectrum of ACS.
The minimal important difference in treadmill endurance test in COPD patients after a comprehensive pulmonary rehabilitation program (PRP)
Authors: Beatriz Manzano, Josiane Marchioro, Joyce Barreto, Oliver Nascimento, José Jardim
Journal: European Respiratory Journal (2011)

Backgroud: As treadmill exercise testing is more representative of daily activity, our aim was to determine the minimal important difference (MID) for treadmill endurance test (TET) capable to detect improvement in functional capacity in patients with COPD after a a 24 sessions PRP.

Material and methods: 100 COPD patients (mean age: 66.6±9.5 years old; FEV1: 44.8±20% pred) were enrolled. Patients performed a 6MWT and a symptom-limited TET at 90% of maximum grade achieved in an incremental test before and after the PRP. The St Georges Respiratory Questionnaire served as anchors for anchor-based MID estimates. Work rate (W), walked distance, endurance time and patients velocity in both tests were calculated.

Results: The TET minimal important difference found for W was 14,337 Joules or 37% increase and for endurance time an increase of 340 s or 77%.

View this table:

Table 1. Changes and minimal important difference (MID) in 6 minute walk test (6MWT) and treadmill endurance test (TET), pre and post pulmonary rehabilitation program





Conclusion: Treadmill endurance test is more representative of changes in functional capacity than 6MWT in COPD patients after a PRP. In addition, work rate seemed to be a good variable to evaluate improvement in exercise capacity after a pulmonary rehabilitation program.
Viral oncogenesis and its role in nonmelanoma skin cancer
Authors: S. Tuttleton Arron, L. Jennings, I. Nindl, F. Rosl, J.N. Bouwes Bavinck, D. Seçkin, M. Trakatelli, G.M. Murphy
Journal: British Journal of Dermatology (2011)

In recent years, the contribution of viruses to cutaneous oncogenesis has steadily gained recognition. The archetype is human herpesvirus 8, which is well established as the causative agent in Kaposi sarcoma. Other viruses believed to play a role in nonmelanoma skin cancer include human papillomavirus and the recently described Merkel cell polyomavirus. We review the mechanisms by which these three viruses interact with the host cell, ultraviolet radiation and immunosuppression to result in carcinogenesis.
Enhanced inflammatory response to formaldehyde in human bronchial epithelial cells
Authors: Ikumi Matsushita, Minako Hijikata, Hideyuki Ito, Naoto Keicho
Journal: European Respiratory Journal (2011)

Formaldehyde (FA) is known as a major chemical substance that may induce sick building syndrome (SBS). The mechanism underlying development of SBS has not been fully elucidated. We hypothesized that low doses of FA may be harmless when airway is intact, but may enhance inflammation when airway is affected by other factors such as microorganisms.  A human bronchial epithelial cell line, BEAS2B cells were exposed to FA (1-10 μM) before and after poly(I:C) (10 μg/ml) stimulation. Expression levels of mRNA of IL-8, RANTES and TLR3 mRNA were measured by real-time RT-PCR and their protein concentrations were determined by using ELISA. Cell signaling pathways possibly involved in the response were further analyzed by Western blotting.  FA after poly(I:C) stimulation significantly enhanced IL-8 mRNA expression and increased IL-8 protein concentrations to lesser extent. Phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal protein kinase (JNK) was enhanced in the cells exposed to FA after poly(I:C) stimulation, whereas p38 MAP kinase was unaffected. This in vitro model suggests that effect of FA is small in normal conditions, but may enhance inflammatory response in pathological conditions via selective activation of inflammatory cell signaling molecules. It may provide insights into pathogenesis of SBS.
Early menarche is associated with increased risk of asthma: Prospective population- based study of twins
Authors: Sofie Lieberoth, Elisabeth Gade, Kirsten Ohm Kyvik, Vibeke Backer, Simon Francis Thomsen
Journal: European Respiratory Journal (2013)

Summary Aim: To examine the association between early menarche and risk of post-menarcheal asthma. Methods: Using data from two multidisciplinary questionnaire surveys, conducted eight years apart, we prospectively studied 10,648 female twins, 12e41 years of age, from the nationwide Danish Twin Registry. Early menarche was defined as menarche before 12 years of age. We performed a cohort analysis and a co-twin control analysis including twin pairs discordant for incident asthma. Results: Early menarche was observed in 9.3% of the individuals. The eight-year cumulative incidence of asthma was higher in girls with early menarche compared to girls without early menarche (7.4 vs. 4.5%), OR Z 1.71 (1.31e2.22), p < 0.001; also after adjustment for BMI, current age, physical activity, education, and smoking, OR Z 1.53 (1.15e2.04), p Z 0.003. The unadjusted risk of asthma was increased by 8% (1e15%), p Z 0.041 per year earlier menarche occurred. Among 167 twin pairs discordant for incident asthma, there was a non-significant tendency towards early menarche being more common in the asthmatic than the nonasthmatic co-twin (12.0 vs. 9.6%), OR Z 1.57 (0.61e4.05), p Z 0.350. The risk of asthma was not uniform in discordant monozygotic and dizygotic twins. Conclusion: Early menarche is associated with increased risk of asthma among Danish female twins independently of BMI, age, physical activity, educational level and smoking. Results indicate a complex relationship possibly mediated through innate and non-genetic effects.
Risk of Advanced Age-Related Macular Degeneration after Cataract Surgery in the Age-Related Eye Disease Study
Authors: Emily Y. Chew, Robert D. Sperduto, Roy C. Milton, Traci E. Clemons, Gary R. Gensler, Susan B. Bressler, Ronald Klein, Barbara E.K. Klein, Frederick L. Ferris
Journal: Ophthalmology (2008)
Treatment of relapsed Hodgkin's disease using a weekly chemotherapy of short duration: Results of a pilot study in 20 patients
Authors: J.A. Radford, D. Crowter
Journal: Annals of Oncology (1991)

Twenty patients with relapsed Hodgkin's disease have been treated with a weekly regimen of chemotherapy (VAPEC-B) comprising Adriamycin 35 mg/m2 i.v. weeks 1, 3, 5, 7, 9, 11; cyclophosphamide 350 mg/m2 i.v. weeks 1, 5, 9; etoposide 100 mg/m2 p.o. daily for 5 days, weeks 3, 7, 11; vincristine 1.4 mg/m2 i.v. weeks 2, 4, 6, 8, 10; bleomycin 10 mg/m2 i.v. weeks 2, 6, 10 and prednisolone 50 mg p.o. daily weeks 1-5, 25 mg p.o. daily weeks 6-11. All had previously received an Adriamycin containing combination and in nine cases this was for relapse following MVPP. In all but one case relapse occurred less than one year after the completion of previous treatment and in 14 cases, disease recurred within 24 weeks. Thirteen patients had extra-nodal involvement. Following six weeks of treatment 14 patients had responded (6 CR; 4 CR, uncertain; 4 PR), four had stable disease, one had progressed and one had died of sepsis. Fourteen patients proceeded to high dose cyclophosphamide and BCNU with autologous bone marrow rescue and seven of these are progression free between 4 and 156 weeks later. High dose therapy was not possible in five patients, three of whom achieved CR. Of these, two (one with bulky nodal disease and skin infiltration; one with extensive bone marrow involvement) are alive and relapse free without further treatment at 95 and 114 weeks. Overall, the regimen was well tolerated but haematological toxicity was moderate or severe in ten patients and four were admitted to hospital for treatment of suspected or confirmed septicaemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract 11: Xenogen-free In Vitro Differentiation and Expansion of Human Pluripotent Stem Cell-Derived Cardiovascular Progenitor Cells
Authors: Xianmei Meng, Anne Knopf, Agustin Vega-Crespo, James Byrne, Ben Van Handel, Ali Nsair
Journal: Circulation Research (2014)

Background: Human pluripotent stem cell-derived cardiovascular progenitor cells (hPSC-CPCs) represent a tractable option for cell-based therapy for heart disease. However, to be clinically relevant, these cells must be derived under good manufacturing practices (GMP)-compatible conditions and produced in great enough quantities to treat adult patients. Here we sought to demonstrate for the first time the generation and expansion of clinically relevant numbers of hPSC-CPCs in xenogen-free protocol. Methods and Results: GMP-grade human induced pluripotent stem cells (GMP-hiPSCs) and human embryonic stem cells (H1 and H9) were dissociated into single cells and cultured in low attachment dishes to differentiate into CPCs in StemPro medium including small molecules and human cytokines with high efficiency of 86%, 80% and 66% for GMP-hiPSCs, H1 and H9, respectively (Figure 1). All hPSC-CPCs possessed trilineage differentiation potentials, as shown by differentiation into endothelial and smooth muscle cells and functional cardiomyocytes (Figure 2). Moreover, sorted hPSC-CPCs expanded &gt;5 fold in 10 days in xenogen-free conditions while still maintaining trilineage differentiation potential and an efficiency of ~70% (Figure 3). Conclusions: Here we demonstrate a xenogeny-free CPC derivation and expansion protocol that can generate clinically relevant numbers of GMP-grade cardiovascular progenitors that could be used in a clinical setting.
Comparison of neuropsychologic functioning and clinical indicators of neurotoxicity in long-term survivors of childhood leukemia given cranial radiation or parenteral methotrexate: a prospective study.
Authors: J Ochs, R Mulhern, D Fairclough, L Parvey, J Whitaker, L Ch'ien, A Mauer, J Simone
Journal: Journal of Clinical Oncology (1991)

We prospectively compared neuropsychologic functioning and clinical indicators of neurotoxicity in 49 consecutive childhood leukemia patients in long-term continuous complete remission (CR) who had received two different regimens of CNS prophylaxis by random assignment. Twenty-three patients were treated with 1,800 cGy cranial radiation and intrathecal methotrexate (RT group) and 26 with parenteral methotrexate only (MTX group). Over half of the RT group had somnolence syndrome, and four developed cerebral calcifications late in their clinical course. Abnormal electroencephalograms (EEGs) were seen in 15 patients in the MTX group, and six had early, transient white-matter hypodensities apparent on computed tomographic (CT) scans. Mean scores on standard tests of intelligence and academic achievement, administered after remission induction and again at a median of 6 years after treatment cessation, did not differ significantly between the two groups. However, statistically significant decreases in overall and verbal intelligence quotients (IQs) and in arithmetic achievement were found within both treatment groups. Sixteen of 26 in the MTX group and 14 of the 23 in the RT group had clinically important decreases (greater than or equal to 15 points) on one or more neuropsychologic measures. These changes did not correlate with findings on CT scans, EEGs, or other clinical signs of neurotoxicity. We conclude that 1,800 cGy cranial radiation and parenteral methotrexate, as used in this study, are associated with comparable decreases in neuropsychologic function.