tbuckley/cabot-search huggingface dataset:
Number of tests and the time needed to fulfil the quality criteria for plethysmographic measurements
Authors: Diana Ionita, Carmen Stroescu, Gabriela Weiss, Ileana Stoicescu, Madalina Burecu, Camelia Nita, Alina Croitoru, Daniela Dospinoiu, Felicia Cojocaru, Irina Strambu
Journal: European Respiratory Journal (2011)

Aim:  Assessing the number of tests and the time needed to obtain quality sessions of body-plethysmography.   Subjects and methods:  Body-plethysmography was performed in healthy subjects and in patients familiar with the testing, in order to obtain at least three acceptable measurements with repeatable parameters (at least four from the list: Raw, IC, VC, FRC and TLC). The number of tests and the time to obtain quality measurements were noted.   Results:  One hundred and eighteen body-plethysmography sessions were performed in 10 weeks: 8 in healthy subjects, 73 in COPD patients and 37 in patients with other respiratory diseases.  All the subjects obtained at least 3 acceptable tests and had repeatable values for at least 3 parameters. One hundred and twelve subjects (95%) obtained repeatable values for 4 parameters and 92 subjects (78%) for all the 5 tested parameters.  In 13 subjects only 3 tests were needed to obtain repeatable values for the tested parameters, 22 subjects needed 4 tests, 26 subjects – 5 tests, 45 subjects – 6 tests and 12 subjects performed 7 tests.  The time needed to obtain correct sessions varied between 4 and 16 minutes (mean 9, mode 7 minutes), without counting interpretation, patient or device preparation, and infection control procedures.  No significant differences were seen in age, gender or FEV1 values between the subjects that obtained repeatable values after 3 or 4 tests versus (vs.) >4 tests, in 3-7 minutes vs. >7 minutes, for 4 vs. 5 parameters (p=NS for all tested associations).   Conclusion:  Three to seven tests and 4-16 minutes were needed to obtain quality sessions in body-plethysmography. The data will help scheduling the tests and for quality control.
Hyperinflation and health status contribute to 6-minute walk distance in COPD, contrary to airway inflammation
Authors: Jorine E. Hartman, H. Marike Boezen, Dirkje S. Postma, Peter J. Sterk, Pieter S. Hiemstra, Thérèse S. Lapperre, Mathieu H.G. de Greef, Nick H.T. ten Hacken
Journal: European Respiratory Journal (2011)

Rationale:  COPD is a chronic inflammatory airway disease that often limits functional exercise capacity in many patients. Airway inflammation has shown to be associated with bronchial hyperresponsiveness (BHR) and hyperinflation in COPD.   Aim:  To assess if sputum inflammation and BHR contribute to functional exercise capacity (assessed by 6-MinuteWalktest (6MWT)) next to lung function, health related quality of life (HRQL) and health status in COPD.   Methods:  108 COPD patients (GOLD stage II & III) participating in the GLUCOLD study [1] (87% male, median (range) FEV 1 %pred 64% (41-78), mean (sd) 6MWT-distance (6MWD) 551 meter (74)). Measurements at baseline: PC 20 methacholine, induced sputum, 6MWT, bodyplethysmography, RAND-36 and Clinical COPD Questionnaire (CCQ). Variables tending to be associated with 6MWD univariately (p 1 .   Results:  Higher RV%pred (b= -0.440, p=0.037), lower RAND-36 “Physical functioning” domainscore (b=0.888, p=0.043) and higher CCQ total score (b= -20.79, p=0.031) were independent contributors of lower 6MWD. Furthermore, higher age (b= -3.56, p=0.000) was associated with lower 6MWD. Induced sputum and PC 20 methacholine were not associated with 6MWD.   Conclusion:  This study shows that increased sputum inflammation and BHR do not contribute to lower 6MWD in patients with moderate to severe COPD, yet markers of hyperinflation and health status are important determinants. A prospective analysis in this cohort will be performed to investigate if reduced inflammation causes less hyperinflation and improved exercise tolerance.   Reference:   1Lapperre ea. Ann Intern Med 2009;151:517-527.
Abstract 75: TNF Receptor 1 Signaling: a Mechanistic Link between Cardiac Inflammation and Fibrosis
Authors: Clemens Duerrschmid, Yanlin Wang, Mark L Entman, Sandra B Haudek
Journal: Circulation Research (2014)

Background: We previously showed in several models of cardiac hypertrophy and failure that, in the absence of cell death, cardiac interstitial fibrosis was mediated by the uptake of monocyte-derived fibroblast precursor cells; fibrosis and concurrent cardiac remodeling were blocked by deletion of monocyte chemoattractant protein-1 (MCP-1), as well as of tumor necrosis factor receptor-1 (TNFR1). We now investigated the cellular origin, kinetics of uptake, and subpopulation of fibroblast precursors in the angiotensin-II (Ang-II)-challenged heart. Methods: Mice with genetic deletion of TNFR1 (TNFR1-KO mice) were irradiated and rescued with bone marrow from wild-type (WT) mice, and were subjected to continuous infusion of Ang-II for 7 days. Flow cytometry was performed on isolated cells, immunostaining on perfusion-fixed tissue, quantitative PCR on whole heart mRNA isolations. Results: In WT mice, Ang-II induced the early uptake of monocytes which became M1 macrophages (CD86+CD45+) in an M1/Th1 environment. Monocytes entering the heart after 2-3 days polarized to M2 macrophages (CD301+CD45+) in an M2/Th2 milieu with concurrent appearance of collagen-producing CD301+ fibroblasts. M1 cells produced TNF, whereas M2 cells did not; both expressed TNFR1. Ang-II-exposed TNFR1-KO hearts showed similar cardiac infiltration of M1 cells, but the amount of M2 cells was significantly lower. They also had reduced expression of M1 and M2 cytokines, but not of Th1 and Th2 interleukins. Transplantation of WT bone marrow to TNFR1-KO mice before Ang-II exposure restored cardiac fibrosis, uptake of M2 cells, and expression of cytokines to levels observed in Ang-II-exposed WT animals. Many TNFR1+ cells in chimeric TNFR1-KO/WT were committed to the fibroblast lineage. Conclusion: Our data show that monocytic fibroblast precursor cells originated in the bone marrow, and that signaling through TNFR1 was required for their uptake and maturation into collagen-producing M2/fibroblasts that mediated the development of cardiac fibrosis in response to Ang-II. They also suggest a mechanistic link between inflammation and fibrosis, i.e. pro-inflammatory, M1-produced TNF initiates pro-fibrotic M2/fibroblast maturation via TNFR1 signaling.
Exercise induced reduction in dynamic hyperinflation after interval training with oxygen breathing
Authors: Janos Varga, Bettina Pogany, Eva Mathene Koteles, Attila Somfay
Journal: European Respiratory Journal (2012)

Bakground: Exercise training reduces exercise induce dynamic hyperinflation (DH) at submaximal exercise (80% of peak work rate) in patients with COPD. Oxygen has dose-dependent effect (maximal at FiO2:0.3) on operating lung volumes in COPD.

Methods: 10 COPD patients with moderate obstruction (FEV1: 53±12%pred, age: 63±10 yrs, BMI: 26±4 kg/m2) performed an incremental exercise test to maximal exercise tolerance, and two constant work rate test (CWR, 80% of peak work rate) with inspiratory capacity (IC maneuver for DH) in every 2 minutes before and after training. Patients performed interval training (1 minute 40% and 1 minute 80% of peak work rate) 3 times a week for 8 weeks breathing oxygen (5 patients 3L/min., group O) or compressed air (5 patients 3 L/min., group C) during training.

Results: The initial peak work rate did not differ significantly between the groups (O: 94±18 vs. C: 86±19 W). Endurance improved in both group (O: 425±110 vs. 630±122, C:370±120 vs. 555±126 sec, p<0.05), oxygen uptake increased in group O (VO2 O:1.20±0.12 vs. 1.36±0.10 L/min., p<0.05) after training. In group O, there was a tendency to reduction in DH after training (IC 1: 2,33±0,62 vs. 2,44±0,90; 2: 2,25±0,73 vs. 2,37±0,94; 3: 2,36±0,96 vs. 2,55±0,97; 4: 2,24±1,00 vs. 2,36±1,01; 5: 2,24±1,00 vs. 2,36±1,01; 6: 2,23±0,97 vs. 2,33±1,00; 7: 2,36±0,73 vs. 2,00±1,02 L). IC did not change in group C.

Conclusion: The pilot study revealed less hyperinflation tendency and improved oxygen uptake in group O, which might refer to better physiologic training effect.
Comparison of DNA methylation profiles between airway epithelium and proxy tissues
Authors: Rossa Brugha, Robert Lowe, John Henderson, John Holloway, Vardhman Rakyan, Seif Shaheen
Journal: European Respiratory Journal (2013)

To date, epidemiological studies of DNA methylation and respiratory disease have measured methylation predominantly in blood, or sometimes in buccal samples, because these sources are readily accessible. However, given tissue specificity of DNA methylation, these tissues may not allow reliable inferences about methylation in the lung. We sought to establish which tissue (nasal, buccal, or blood) had the closest methylation profile to that of airway epithelium.  Samples of airway epithelial cells (by blind brushing via endotracheal tube), blood, nasal epithelial and buccal cells were obtained from six children undergoing general anaesthetic for elective tonsillectomy. Following bisulphite conversion, CpG site methylation was analysed at 450,000 sites using the Illumina 450k array.  Nineteen samples were suitable for analysis. Hierarchical clustering demonstrated that the methylation profile of nasal epithelial cells had the greatest similarity to that of airway epithelial cells; the methylation profile of buccal cells was moderately similar; and that of blood was least similar. When we quantified this by calculating a standard Euclidean distance of the average methylation beta values for each tissue from the average value for airway epithelial cells, the distances for nasal, buccal and blood were, respectively, 46.1, 72.3, and 91.4.  DNA methylation in blood poorly reflects methylation in airway epithelium. Given that direct airway sampling is not feasible in epidemiological studies, future population studies of DNA methylation and airway disease should measure methylation either in buccal cells, or preferably in nasal epithelial cells, in order to best capture disease relevant methylation marks.
Functional respiratory status in preterm children with and without bronchopulmonary displasia
Authors: Irina Davydova, Tatiana Turti, Victor Altunin
Journal: European Respiratory Journal (2012)

Differences of Tidal Breath (TB) parameters in preterm infants with and without Bronchopulmonary Displasia (BPD) may be connected not only with consequences of Mechanical Lung Ventilation (MLV), but with a structural immaturity of the respiratory system of preterm infants.

Aim : to identify differences of TB-parameters in preterm infants with and without Bronchopulmonary Displasia up to 2 years old.

Material and Methods: TB measurements in 33 preterm infants without BPD (1) and 11 ones with BPD (2) with corrected age 1-3 months were performed (MasterScreen, Jaeger, Germany). The median gestational age in group 1 was 32 weeks (29-35w), height was 56.7cm (49-63.7cm) and weight – 5.0kg (3.0-7.0kg), and in group 2 - 29 weeks (27-32w), 54.5cm (47-63cm) and 4.8kg (2.9-6.8kg). 10–20 breathing cycles were evaluated. Six TB parameters were analyzed, but only two were significant: time of reach Peak Tidal Expiratory Flow as a proportion of total Expiratory time (tPTEF%tE) and expiratory Volume till Peak Tidal Expiratory Flow as a proportion of total expiratory Volume (VePTEF%Ve).

Results: Significant differences between infants with and without BPD were not found in anthropometric parameters with U-test (p<0.05). On comparison of TB-parameters between both patient's groups accordingly to the p-value of the ANOVA we found significantly decreased tPTEF%tE and VePTEF%Ve in group 1 as well as in group 2 (p=0.04 and p=0.03). In infants with BPD the mean tPTEF%tE was 19.0% (12.0-33.3) and mean VePTEF%Ve was 22.5% (17.8-32.2) in comparison to tPTEF%tE 25.6% (16.8-36.9) and VePTEF%Ve 27.3% (19.7-36.7) in infants without BPD.
Ultrastructure of Transplantable Mouse Hepatomas With Different Growth Rates&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Linda E. Malick
Journal: JNCI Journal of the National Cancer Institute (1972)

Ultrastructural studies of 4 transplantable mouse hepatomas BC3, BH3, BRL, and BNL, in inbred BUB mice, which have 3 different growth rates, revealed no correlation between the cellular differentiation of these hepatomas and their growth rates. Each tumor had a unique set of ultrastructural characteristics. The endoplasmic reticulum of the slow-growing tumor was less well developed than that of the 3 faster growing tumors. Golgi complexes in the tumors with the intermediate growth rate, BH3 and BRL, had dilated cisternae and vesicles filled with material indicating activity, whereas those of both the fast- and slow-growing tumors appeared inactive. Glycogen and lysosomes were present in all the tumors. Microbodies appeared normal in slow-growing hepatoma BC3, were rare in hepatoma BRL, and absent in the remaining 2 tumors. Hypertrophied nucleoli were present in all but the slowest growing tumor. The only nuclear alteration apparent in this tumor was the increased size of the perichromatinic granules. Junctional complexes in all 4 hepatomas were less numerous and frequently smaller than in normal hepatocytes. Although the presence of tight or gap junctions in the hepatomas had no obvious relation to growth rate or metastasizing capacity, the proportion of desmosomes to tight or gap junctions in a particular tumor might be related to its invasive properties.—J Natl Cancer Inst 49: 1039–1055, 1972.
Comparative pharmacokinetic studies of three asparaginase preparations.
Authors: B L Asselin, J C Whitin, D J Coppola, I P Rupp, S E Sallan, H J Cohen
Journal: Journal of Clinical Oncology (1993)

PURPOSE As part of pharmacologic studies of asparaginase (ASNase), we determined the half-life of ASNase activity and protein, and the effect of dose, repeated doses, different drug preparations, and hypersensitivity reactions on the half-life (t1/2) of serum ASNase activity. PATIENTS AND METHODS We measured ASNase activity (spectrophotometric assay) in serum samples obtained from patients with acute lymphoblastic leukemia (ALL) at various times during their therapy with intramuscular ASNase. ASNase protein was measured by enzyme-linked immunoadsorbent assay (ELISA). RESULTS Studies following the initial dose of Escherichia coli-derived ASNase demonstrated no difference in apparent t1/2 following 25,000 IU/m2 versus 2,500 IU/m2 (1.24 v 1.35 days, P = .2). The apparent t1/2s following maintenance doses of E coli ASNase (middle dose t1/2, 1.28 days, or last dose t1/2, 1.14 days) showed no difference when compared with the initial dose of ASNase (P = .3 to .9). There was no significant difference between the apparent t1/2s of ASNase activity and ASNase protein (n = 8, P = .2 to .6). The serum t1/2 was 0.65 and 5.73 days for patients receiving Erwinia or polyethylene glycol (PEG)-modified E coli ASNase, respectively, as the induction dose. ASNase activity was undetectable in sera of four patients studied in the week following an anaphylactic reaction to E coli ASNase and the t1/2 was significantly shorter in five patients with a history of allergic reaction to E coli ASNase who were studied following a dose of PEG ASNase, (t1/2, 1.80 days). CONCLUSION We conclude that (1) the apparent t1/2 of ASNase is dependent on enzyme preparation used, but is not affected by dose or by repeated use; (2) the apparent t1/2 of E coli ASNase as a protein is the same as the apparent t1/2 of enzymatic activity; and (3) patients who have had a hypersensitivity reaction to E coli ASNase have a decreased apparent t1/2 with both E coli and PEG ASNase.
CPAP therapy withdrawal – A model to evaluate treatments for OSA
Authors: Malcolm Kohler, Anne-Christin Stoewhas, Konrad E. Bloch, Erich W. Russi, John R. Stradling
Journal: European Respiratory Journal (2011)

Background: Evaluating OSA therapies by recruiting previously untreated patients in randomised controlled trials is time consuming and expensive. A more efficient model to investigate effects of OSA treatments could be during CPAP withdrawal. There is no data from randomized controlled trials defining the effects of CPAP-withdrawal on OSA, thus we determined the effects of two weeks CPAP withdrawal on sleep-disordered breathing, sleepiness and psychomotor performance.  Methods: 41 OSA patients on CPAP were randomized to either withdraw CPAP (sham-CPAP) or continue CPAP for 2 weeks. At baseline, 1 and 2 weeks, apnea/hypopnea index (AHI), oxygen desaturation index (ODI), Epworth sleepiness scale (ESS), Osler test, divided attention driving simulator (DADS) and psychomotor vigilance test (PVT) were assessed.  Results: Withdrawal of CPAP increased AHI at 1 and 2 weeks (mean difference in AHI change +31.9 (95%CI 20.1,43.7) and +33.5 (95%CI 22.4,44.6), respectively) and ODI (mean difference in ODI change +26.3 (95%CI 16.6,36.0) and +26.4 (95%CI 16.1,36.8), respectively) in comparison to continuation of CPAP (p  Conclusions: CPAP withdrawal leads to a fast recurrence of OSA and a slow return of subjective sleepiness, but is not associated with deterioration in psychomotor performance within 2 weeks. Therefore, this model seems suitable and safe to evaluate treatment effects on OSA.
Reflectance confocal microscopy for monitoring the density of<i>Demodex</i>mites in patients with rosacea before and after treatment
Authors: E.C. Sattler, V.S. Hoffmann, T. Ruzicka, T.V. Braunmühl, C. Berking
Journal: British Journal of Dermatology (2015)

Demodex mites seem to serve as a pathogenic trigger in many Demodex-associated diseases such as rosacea. In facial skin of patients with rosacea significantly higher numbers of Demodex mites have been shown compared with healthy controls. Reflectance confocal microscopy (RCM) allows the detection and quantification of Demodex mites in vivo noninvasively. It is hypothesized that a reduction of Demodex mites under rosacea therapy can be monitored by RCM.To use RCM to monitor the density of Demodex mites in patients with rosacea before and after treatment.In 25 patients with facial rosacea RCM was performed before and after therapy. Mosaics of 5 × 5 mm(2) and 8 × 8 mm(2) were scanned, and the total numbers of mites per follicle and per area were counted, along with the number of follicles per area.In all patients Demodex folliculorum could be detected and quantified using RCM. RCM showed significant differences pre- and post-treatment (P = 0.0053 for 5 × 5 mm(2) and P < 0.001 for 8 × 8 mm(2)). The mean numbers of mites per follicle were 0.63 (range 0.16-2.28) per 8 × 8 mm(2) area and 0.70 (range 0.11-2.20) per 5 × 5 mm(2) area before treatment, and 0.41 (range 0.074-1.75) and 0.51 (range 0.094-1.70), respectively, after treatment. The corresponding mean numbers of mites were 155 (range 45-446) and 86.2 (range 12-286), respectively, before treatment and 96.2 (range 18-363) and 58.5 (range 12-230), respectively, after treatment.By RCM, a reduction in the density of Demodex mites in facial skin of patients with rosacea under therapy, correlating to clinical improvement, can be quantified and monitored noninvasively. Possible reasons for this therapeutic effect are discussed.
Paclitaxel Versus Doxorubicin as First-Line Single-Agent Chemotherapy for Metastatic Breast Cancer: A European Organization for Research and Treatment of Cancer Randomized Study With Cross-Over
Authors: R. Paridaens, L. Biganzoli, P. Bruning, J.G. M. Klijn, T. Gamucci, S. Houston, R. Coleman, J. Schachter, A. Van Vreckem, R. Sylvester, A. Awada, J. Wildiers, M. Piccart
Journal: Journal of Clinical Oncology (2000)

To compare the efficacy of paclitaxel versus doxorubicin given as single agents in first-line therapy of advanced breast cancer (primary end point, progression-free survival ¿PFS) and to explore the degree of cross-resistance between the two agents.Three hundred thirty-one patients were randomized to receive either paclitaxel 200 mg/m(2), 3-hour infusion every 3 weeks, or doxorubicin 75 mg/m(2), intravenous bolus every 3 weeks. Seven courses were planned unless progression or unacceptable toxicity occurred before the seven courses were finished. Patients who progressed within the seven courses underwent early cross-over to the alternative drug, while a delayed cross-over was optional for the remainder of patients at the time of disease progression.Objective response in first-line therapy was significantly better (P =.003) for doxorubicin (response rate ¿RR, 41%) than for paclitaxel (RR, 25%), with doxorubicin achieving a longer median PFS (7.5 months for doxorubicin v 3.9 months for paclitaxel, P <.001). In second-line therapy, cross-over to doxorubicin (91 patients) and to paclitaxel (77 patients) gave response rates of 30% and 16%, respectively. The median survival durations of 18.3 months for doxorubicin and 15.6 months for paclitaxel were not significantly different (P =.38). The doxorubicin arm had greater toxicity, but this was counterbalanced by better symptom control.At the dosages and schedules used in the present study, doxorubicin achieves better disease and symptom control than paclitaxel in first-line treatment. Doxorubicin and paclitaxel are not totally cross-resistant, which supports further investigation of these drugs in combination or in sequence, both in advanced disease and in the adjuvant setting.
Maternal history of adenotonsillectomy predicts severity of OSA in children with snoring
Authors: Emmanouel Alexopoulos, George Haritos, Georgia Malakasioti, Vasiliki Varlami, Konstantinos Gourgoulianis, Athanasios Kaditis
Journal: European Respiratory Journal (2013)

Recognition of subgroups of children with snoring who are at risk of moderate-to-severe obstructive sleep apnea (OSA), and thus potential candidates for adenoidectomy and/or tonsillectomy (AT), may facilitate selection of snorers with priority for polysomnography. We hypothesized that paternal and maternal history of AT are risk factors for moderate-to-severe OSA in children with snoring. Methods: Data of children with snoring who underwent polysomnography at the Larissa University Hospital Sleep Disorders Laboratory from January 2005 till December 2012 were analysed retrospectively. Only subjects without history of neuromuscular, craniofacial or genetic disorders were included in the study. Paternal and maternal history of AT were the explanatory variables and apnea-hypopnea index (AHI) > 5 episodes/h (moderate-to-severe OSA) was the outcome measure. Results: A total of 758 children were included in the analysis (2-16 yo); 152 (20%) of them had paternal history of AT and 80 (10.6%) had maternal history of AT. Maternal-but not paternal-history of AT was significantly associated with the presence of moderate-to-severe OSA after adjustment for gender, presence of tonsillar hypertrophy and obesity [odds ratio (95% CI): 1.87 (1.12-3.11); p=0.02 and 1.51 (0.99-2.29); p=0.06, respectively]. Conclusions: Among children with snoring, maternal history of AT is a significant risk factor for moderate-to-severe OSA.