bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aminoglycoside suppression of nonsense mutations in severe hemophilia
Authors: James Paula D. , Raut Sanj , Rivard Georges E. , Poon Man-Chiu , Warner Margaret , McKenna Susan , Leggo Jayne , Lillicrap David 
Published: July 2005

AbstractAminoglycoside antibiotics exhibit their bactericidal effect by interfering with normal ribosomal activity. In this pilot study, we have evaluated the effect of the aminoglycoside antibiotic gentamicin on the factor VIII (FVIII) and IX levels of severe hemophiliacs with known nonsense mutations. Five patients were enrolled and each patient was given 3 consecutive days of gentamicin at a dose of 7 mg/kg intravenously every 24 hours. Two patients (patient no. 1: hemophilia A, Ser1395Stop; and patient no. 5: hemophilia B, Arg333Stop) showed a decrease in their activated partial thromboplastin time (aPTT), an increase in their FVIII (0.016 IU/mL, 1.6%) or FIX (0.02 IU/mL, 2%) levels, and an increase in thrombin generation. The remaining 3 patients (patient no. 2: hemophilia B, Arg252Stop; patient no. 3: hemophilia A, Arg2116Stop; and patient no. 4: hemophilia A, Arg427Stop) showed no response in the aPTTs or factor levels, but one (patient no. 2: hemophilia B, Arg252Stop) showed an increase in the factor IX antigen level (2%-5.5%) that persisted throughout the period of the study and was concordant with an increase in thrombin generation. Gentamicin is unlikely to be an effective treatment for severe hemophilia due to its potential toxicities and the minimal response documented in this report. This study, however, does provide a proof of principle, suggesting that ribosomal interference with a less toxic agent may be a potential therapeutic mechanism for severe hemophilia patients with nonsense mutations.
Epidemiological evidence of effects of coarse airborne particles on health
Authors: Brunekreef B. , Forsberg B. 
Published: July 2005

Studies on health effects of airborne particulate matter (PM) have traditionally focused on particles <10 μm in diameter (PM10) or particles <2.5 μm in diameter (PM2.5). The coarse fraction of PM10, particles >2.5 μm, has only been studied recently. These particles have different sources and composition compared with PM2.5. This paper is based on a systematic review of studies that have analysed fine and coarse PM jointly and examines the epidemiological evidence for effects of coarse particles on health.Time series studies relating ambient PM to mortality have in some places provided evidence of an independent effect of coarse PM on daily mortality, but in most urban areas, the evidence is stronger for fine particles. The few long-term studies of effects of coarse PM on survival do not provide any evidence of association.In studies of chronic obstructive pulmonary disease, asthma and respiratory admissions, coarse PM has a stronger or as strong short-term effect as fine PM, suggesting that coarse PM may lead to adverse responses in the lungs triggering processes leading to hospital admissions. There is also support for an association between coarse PM and cardiovascular admissions.It is concluded that special consideration should be given to studying and regulating coarse particles separately from fine particles.
Plasma concentrations of dietary and nondietary antioxidants are low in severe asthma
Authors: Misso N. L. A. , Brooks-Wildhaber J. , Ray S. , Vally H. , Thompson P. J. 
Published: July 2005

Low antioxidant levels and oxidative stress due to airway inflammation may be important determinants of asthma severity. The objective of the present study was to determine whether lower antioxidant intake and plasma antioxidant concentrations are associated with more severe asthma.Dietary antioxidant intakes and asthma severity were assessed using questionnaires, and plasma concentrations of ascorbic acid, vitamin E, carotenoids, bilirubin, albumin, uric acid and total antioxidant status were measured in 53 mild-to-moderate and 28 severe asthmatic patients and in 43 nonasthmatic subjects.Vitamin C and carotene intakes were lower in males than females and were particularly low in males with severe asthma. Plasma ascorbic acid was lower in severe (31.9±3.6 µM) compared with mild-to-moderate asthmatic (52.3±2.6) or control subjects (52.7±2.9). Low plasma ascorbic acid (odds ratio (OR) 0.93; 95% confidence interval (CI) 0.9–0.97), bilirubin (OR 0.69; 95% CI 0.51–0.93) and increased plasma cholesterol (OR 1.98; 95% CI 1.05–3.73) were independently associated with severe asthma. Albumin was positively and cholesterol negatively correlated with lung function.Low plasma concentrations of specific antioxidants are associated with more severe asthma. Increased antioxidant intake may help reduce the burden of severe asthma, particularly in males.
Are patients with COPD psychologically distressed?
Authors: Wagena E. J. , Arrindell W. A. , Wouters E. F. M. , van Schayck C. P. 
Published: July 2005

This study was designed to assess the level of psychological distress in a heterogeneous group of patients with chronic obstructive pulmonary disease (COPD), and compare them with the general population and psychiatric outpatients.A total of 118 patients with COPD, a random sample of 500 subjects from the general population and 500 psychiatric outpatients participated in this study. The Dutch version of the Symptom Checklist-90-Revised was used to assess general psychological distress.The sample of patients with COPD experienced significantly more psychological distress than the general population and significantly less than psychiatric outpatients. Furthermore, no significant association was found between the severity of the pulmonary disease and the level of psychological distress, although patients with severe or very severe COPD appeared to be at increased risk of depression. Lastly, the pattern of psychological complaints seems comparable in depressed patients with COPD and psychiatric outpatients. Once patients with COPD report suffering from depressive symptoms, the level of distress seems to increase to that found in psychiatric outpatients.In conclusion, in clinical settings in which psychological complaints are not routinely assessed, the Beck Depression Inventory and Symptom Checklist-90-Revised are very useful for drawing attention to depression and psychological distress.
Factors affecting survival of hospitalised patients with COPD
Authors: Gunen H. , Hacievliyagil S. S. , Kosar F. , Mutlu L. C. , Gulbas G. , Pehlivan E. , Sahin I. , Kizkin O. 
Published: July 2005

Factors determining in-hospital mortality and long-term survival of patients hospitalised with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are not precisely understood. The aim of the present study was to assess the parameters related to in-hospital mortality and long-term survival after hospitalisation of patients with AECOPD.Clinical and epidemiological parameters on admission in 205 consecutive patients hospitalised with AECOPD were prospectively assessed. Patients were followed-up for 3 yrs. Factors determining short- and long-term mortality were analysed.In total, 17 patients (8.3%) died in hospital. In-hospital mortality was significantly associated with lower arterial oxygen tension (Pa,O2), higher carbon dioxide arterial tension, lower arterial oxygen saturation and longer hospital stay. The overall 6-month mortality rate was 24%, with 1-, 2- and 3-yr mortality rates of 33%, 39% and 49%, respectively. Cox regression analysis revealed that long-term mortality was associated with longer disease duration (relative risk (RR) = 1.158), lower albumin (RR = 0.411), lowerPa,O2(RR = 0.871) and lower body mass index (RR = 0.830). When the model was run for the time elapsed since first hospitalisation, it also appeared as statistically significant (RR = 1.195).These findings show that patients hospitalised with acute exacerbations of chronic obstructive pulmonary disease have poor short- and long-term survival. Prediction of survival status may be enhanced by considering arterial oxygen tension, albumin, body mass index, disease duration and time elapsed since the first hospitalisation.
Impact of obstructive sleep apnoea on left ventricular mass and global function
Authors: Dursunoglu D. , Dursunoglu N. , Evrengül H. , Özkurt S. , Kuru Ö. , Kiliç M. , Fisekci F. 
Published: July 2005

Obstructive sleep apnoea syndrome (OSAS) might be a cause of heart failure. The present study aimed to assess left ventricular mass and myocardial performance index (MPI) in OSAS patients.A total of 67 subjects without any cardiac or pulmonary disease, referred for evaluation of OSAS, had overnight polysomnography and echocardiography. According to apnoea-hypopnoea index (AHI), subjects were classified into three groups: mild OSAS (AHI: 5–14; n = 16), moderate OSAS (AHI: 15-29; n = 18), and severe OSAS (AHI: ≥30; n = 33). Thickness of interventricular septum (IVS) and posterior wall (LVPW) were measured by M-mode, along with left ventricular mass (LVM) and LVM index (LVMI). Left ventricular MPI was calculated as (isovolumic contraction time+isovolumic relaxation time)/aortic ejection time by Döppler echocardiography.There were no differences in age or body mass index among the groups, but blood pressures were higher in severe OSAS compared with moderate and mild OSAS. In severe OSAS, thickness of IVS (11.2±1.1 mm), LVPW (11.4±0.9 mm), LVM (298.8±83.1 g) and LVMI (144.7±39.8 g·m−2) were higher than in moderate OSAS (10.9±1.3 mm; 10.8±0.9 mm; 287.3±74.6 g; 126.5±41.2 g·m−2, respectively) and mild OSAS (9.9±0.9 mm; 9.8±0.8 mm; 225.6±84.3 g; 100.5±42.3 g·m−2, respectively). In severe OSAS, MPI (0.64±0.14) was significantly higher than in mild OSAS (0.50±0.09), but not significantly higher than moderate OSAS (0.60±0.10).In conclusion, severe and moderate obstructive sleep apnoea syndrome patients had higher left ventricular mass and left ventricular mass index, and also left ventricular global dysfunction.
Time course of cigarette smoke-induced pulmonary inflammation in mice
Authors: D'hulst A. I. , Vermaelen K. Y. , Brusselle G. G. , Joos G. F. , Pauwels R. A. 
Published: July 2005

Inflammation of the airways and lung parenchyma plays a major role in the pathogenesis of chronic obstructive pulmonary disease. In the present study a murine model of tobacco smoke-induced emphysema was used to investigate the time course of airway and pulmonary inflammatory response, with a special emphasis on pulmonary dendritic cell (DC) populations.Groups of mice were exposed to either cigarette smoke or to control air for up to 24 weeks. In response to cigarette smoke, inflammatory cells (i.e.neutrophils, macrophages and lymphocytes) progressively accumulated both in the airways and lung parenchyma of mice. Furthermore, a clear infiltration of DCs was observed in airways (10-fold increase) and lung parenchyma (1.5-fold increase) of cigarette-exposed mice at 24 weeks.Flow cytometric analysis of bronchoalveolar lavage (BAL) DCs of smoke-exposed mice showed upregulation of major histocompatability complex II molecules and costimulatory molecules CD40 and CD86, compared with BAL DCs of air-exposed mice. Morphometric analysis of lung histology demonstrated a significant increase in mean linear intercept and alveolar wall destruction after 24 weeks of smoke exposure.In conclusion, the time course of the changes in inflammatory and dendritic cells in both bronchoalveolar lavage and the pulmonary compartment of cigarette smoke-exposed mice was carefully characterised.
Breath condensate ammonium is lower in children with chronic asthma
Authors: MacGregor G. , Ellis S. , Andrews J. , Imrie M. , Innes A. , Greening A. P. , Cunningham S. 
Published: July 2005

Exhaled breath condensate pH and ammonium reflect asthmatic status and acute exacerbations in adults. The aim of this study was to assess whether pH and ammonium could reflect asthma and its severity in children.The current study comprised two parts: 1) a cross-section of 74 children with asthma (median age 10.5 yrs) compared with 47 healthy controls (median age 10 yrs); and 2) longitudinal assessment of eight children (mean age 8.5 yrs) admitted with asthma exacerbation. Condensate pH and ammonium were compared with clinical observations.In the cross-sectional part of the study, lower per cent forced expiratory volume in one second was associated with more symptoms and treatment. There was no significant difference between median pH in children with stable asthma (6.05) compared with controls (5.90). Ammonium was significantly lower in children with asthma (median 258 µM) compared with controls (median 428 µM). No association was found between ammonium or pH and lung function or symptom-free days. In the longitudinal study, significant improvements in oxygen saturation and respiratory rate with treatment of an acute exacerbation were not reflected by changes in pH or ammonium.In conclusion, pH does not appear to reflect disease or severity in children with asthma. Ammonium was significantly lower in children with asthma when compared with controls.
Dependency on mask ventilation after acute respiratory failure in the intermediate care unit
Authors: Cuvelier A. , Viacroze C. , Bénichou J. , Molano L. C. , Hellot M-F. , Benhamou D. , Muir J-F. 
Published: July 2005

The predictive factors for long-term dependency (LTD) on noninvasive ventilation (NIV) immediately after acute hypercapnic respiratory failure (AHRF) have not been identified.The present authors studied 42 patients with chronic obstructive pulmonary disease (COPD) and 58 non-COPD patients successfully treated by NIV for an AHRF episode. Parameters at stable state, at admission for AHRF and during a 1-yr follow-up were compared in patients with or without LTD-NIV at discharge.The incidence of LTD-NIV was 39% in non-COPD patients and 19% in COPD patients. Based on multivariate analysis with stepwise logistic regression, lower baseline pH values and noninfectious causes of AHRF were independently associated with LTD-NIV. Mutually adjusted odds ratios were found to be 1.316 (95% confidence interval (CI) = 1.127–1.536) for a 0.01 decrease of baseline pH value and 5.1 (95% CI = 1.8–14.0) for a noninfectious cause of AHRF. Outcome after 1 yr was poor in COPD patients.Long-term dependency on noninvasive ventilation is not an uncommon situation after resolution of an acute hypercapnic respiratory failure episode, especially in patients with non-chronic obstructive pulmonary disease causes of respiratory failure. The present study raises the need for prospective validation of a weaning protocol in patients managed by noninvasive ventilation for an acute hypercapnic respiratory failure episode.
Morbidity and mortality in the surgery arm of EORTC 08941 trial
Authors: Van Schil P. , Van Meerbeeck J. , Kramer G. , Splinter T. , Legrand C. , Giaccone G. , Manegold C. , van Zandwijk N. 
Published: July 2005

Controversial results of surgical treatment after induction chemotherapy, especially in relation to the extent of resection, have previously been reported. Mortality and morbidity were studied in the surgical arm of the European Organisation for Research and Treatment of Cancer (EORTC) 08941 trial.EORTC 08941 is a multicentre, prospective, randomised, phase-III trial of surgical resectionversusradiotherapy in patients with proven stage IIIA-N2nonsmall cell lung cancer after an objective response to platinum-based induction chemotherapy. Operative results in the 167 patients randomised in the surgical arm are presented within this study. Among these patients, one switched to the radiotherapy arm and 17 patients did not get any protocol treatment or information is not yet available.Radical resection with negative surgical margins was obtained in 74 patients (49.7%). In 61 patients (40.9%), a pathological down-staging to N0or N1was present. Operative 30-day mortality was 4.0%. Post-operative complications were mainly pneumonia, respiratory insufficiency, arrhythmias, air leak, cardiac decompensation, empyema and bronchopleural fistula. In total, 12 (8.1%) patients underwent re-operation due to positive margins, haemothorax, empyema and bronchopleural fistula.In conclusion, surgical resection after induction chemotherapy in the multicentre European Organisation for Research and Treatment of Cancer trial has yielded acceptable rates of morbidity and mortality.
Microscopic pulmonary embolisation of an indwelling central venous catheter with granulomatous inflammatory response
Authors: Baydur A. , Koss M. N. , Sharma O. P. , Dalgleish G. E. , Nguyen D. V. , Mullick F. G. , Murakata L. A. , Centeno J. A. 
Published: July 2005

Indwelling catheters can disintegrate into tiny fragments and embolise. Once the fragments are detected radiographically, they can be removed using vascular intervention techniques. Rarely, indwelling catheters dwindle into inextricable pieces that embolise into minute pulmonary vessels and lymphatics, causing granulomatous changes microscopically.The present study reports a 54-yr-old female who had received several indwelling central lines during several abdominal surgeries over a 5-yr period. The patient developed a noncaseating granulomatous skin lesion followed by exertional dyspnoea a few months later. Chest radiographs and computed tomography showed diffuse interstitial infiltrates. Open lung biopsy showed two types of granulomas: 1) peri-lymphangitic and peri-bronchiolar non-necrotising granulomas consistent with sarcoidosis; and 2) distinct foreign body granulomas.In some of the foreign body granulomas, confocal Raman spectroscopy identified the presence of bisphenol-A-polycarbonate, a polymer commonly used in biomedical devices. The patient improved following treatment with prednisone followed by methotrexate.The present case illustrates an interesting combination of two causes of granulomatous disease, the importance of examining all biopsy specimens from sarcoidosis patients for foreign particles and the rare occurrence of microscopic embolisation of catheter fragments to the lung with foreign-body giant cell reaction to them.
P53 and Beta-Catenin Activity during Estrogen treatment of Osteoblasts
Authors: Chandar Nalini , Saluja Rasleen , Lamar Peter C , Kolman Kevin , Prozialeck Walter C 
Published: July 2005

Abstract

Background
This study was undertaken to examine the relationship between the tumor suppressor gene p53 and the nuclear signaling protein beta-catenin during bone differentiation. Cross talk between p53 and beta-catenin pathways has been demonstrated and is important during tumorigenesis and DNA damage, where deregulation of beta catenin activates p53. In this study, we used estrogen treatment of osteoblasts as a paradigm to study the relationship between the two proteins during osteoblast differentiation.

Results
We exposed osteoblast-like ROS17/2.8 cells to 17-beta estradiol (E2), in a short term assay, and studied the cellular distribution and expression of beta-catenin. We found beta-catenin to be up regulated several fold following E2 treatment. Levels of p53 and its functional activity mirrored the quantitative changes seen in beta-catenin. Alkaline phosphatase, an early marker of osteoblast differentiation, was increased in a manner similar to beta-catenin and p53. In order to determine if there was a direct relationship between alkaline phosphatase expression and beta-catenin, we used two different approaches. In the first approach, treatment with LiCl, which is known to activate beta-catenin, caused a several fold increase in alkaline phosphatase activity. In the second approach, transient transfection of wild type beta-catenin into osteoblasts increased alkaline phosphatase activity two fold over basal levels, showing that beta catenin expression can directly affect alkaline phosphatase expression. However increase in beta catenin activity was not associated with an increase in its signaling activity through TCF/LEF mediated transcription. Immunofluorescence analyses of p53 and beta-catenin localization showed that E2 first caused an increase in cytosolic beta-catenin followed by the accumulation of beta-catenin in the nucleus. Nuclear p53 localization was detected in several cells.
Expression of p53 was accompanied by distribution of beta-catenin to the cytoplasm and cell borders. A sub population of cells staining strongly for both proteins appeared to be apoptotic.

Conclusion
These results suggest that interactions between p53 and beta-catenin signaling pathways may play a key role in osteoblast differentiation and maintenance of tissue homeostasis.
Causal thinking and causal language in epidemiology: it's in the details
Authors: Lipton Robert , Ødegaard Terje 
Published: July 2005

AbstractAlthough epidemiology is necessarily involved with elucidating causal processes, we argue that there is little practical need, having described an epidemiological result, to then explicitly label it as causal (or not). Doing so is a convention which obscures the valuable core work of epidemiology as an important constituent of public health practice. We discuss another approach which emphasizes the public health "use value" of research findings in regard to prediction and intervention independent from explicit metaphysical causal claims. Examples are drawn from smoking and lung cancer, with particular focus on the original 1964 Surgeon General's report on smoking and the new version released in 2004. The intent is to help the epidemiologist focus on the pertinent implications of research, which, from a public health point of view, in large part entails the ability to predict and to intervene. Further discussion will center on the importance of differentiating between technical/practical uses of causal language, as might be used in structural equations or marginal structural modeling, and more foundational notions of cause. We show that statistical/epidemiological results, such as "smoking two packs a day increases risk of lung cancer by 10 times" are in themselves a kind of causal argument that are not in need of additional support from relatively ambiguous language such as "smoking causes lung cancer." We will show that the confusion stemming from the use of this latter statement is more than mere semantics. Our goal is to allow researchers to feel more confident in the power of their research to tell a convincing story without resorting to metaphysical/unsupportable notions of cause.