bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of salmeterol on the ventilatory response to exercise in chronic obstructive pulmonary disease
Authors: O'Donnell D.E. , Voduc N. , Fitzpatrick M. , Webb K.A. 
Published: July 2004

This study examined the effects of bronchodilator-induced reductions in lung hyperinflation on breathing pattern, ventilation and dyspnoea during exercise in chronic obstructive pulmonary disease (COPD). Quantitative tidal flow/volume loop analysis was used to evaluate abnormalities in dynamic ventilatory mechanics and their manipulation by a bronchodilator.In a randomised double-blind crossover study, 23 patients with COPD (mean±sem forced expiratory volume in one second 42±3% of the predicted value) inhaled salmeterol 50 µg or placebo twice daily for 2 weeks each. After each treatment period, 2 h after dose, patients performed pulmonary function tests and symptom-limited cycle exercise at 75% of their maximal work-rate.After salmeterolversusplacebo at rest, volume-corrected maximal expiratory flow rates increased by 175±52%, inspiratory capacity (IC) increased by 11±2% pred and functional residual capacity decreased by 11±3% pred. At a standardised time during exercise, salmeterol increased IC, tidal volume (VT), mean inspiratory and expiratory flows, ventilation, oxygen uptake (V'O2) and carbon dioxide output. Salmeterol increased peak exercise endurance,V'O2and ventilation by 58±19, 8±3 and 12±3%, respectively. Improvements in peakV'O2correlated best with increases in peakVT; increases in peakVTand resting IC were interrelated. The reduction in dyspnoea ratings at a standardised time correlated with the increasedVT.Mechanical factors play an important role in shaping the ventilatory response to exercise in chronic obstructive pulmonary disease. Bronchodilator-induced lung deflation reduced mechanical restriction, increased ventilatory capacity and decreased respiratory discomfort, thereby increasing exercise endurance.
Parameters associated with persistent airflow obstruction in chronic severe asthma
Authors: Bumbacea D. , Campbell D. , Nguyen L. , Carr D. , Barnes P.J. , Robinson D. , Chung K.F. 
Published: July 2004

The significance of severe airflow obstruction in severe asthma is unclear. The current study determined whether severe airflow obstruction is related to inflammatory or structural changes in the airways.Patients with severe asthma from a tertiary referral clinic were divided into two groups according to their postbronchodilator forced expiratory volume in one second (FEV1): severe persistent airflow limitation (FEV1<50% predicted; group S; n=37) and no obstruction (FEV1>80% pred; group N; n=29). Smoking history, atopic status, lung function tests, exhaled NO, blood eosinophil count, quality of life scores using St George's Respiratory Questionnaire and high resolution computed tomography (HRCT) of the lungs were assessed.Patients from group S were older and had longer disease duration. There was no difference in smoking history, atopic status, hospital admissions, quality of life scores and amount of treatment with inhaled or oral corticosteroids. Exhaled NO and peripheral blood eosinophils were higher in group S (21.0±2.4versus12.8±2.3 ppb; 0.41±0.06versus0.15±0.03×109cells·L−1, respectively). HRCT scores for bronchial wall thickening and dilatation were higher in group S with no differences in air trapping. Peripheral blood eosinophilia and bronchial wall thickening on HRCT scan were the only parameters significantly and independently associated with persistent airflow obstruction.Patients with severe asthma and irreversible airflow obstruction had longer disease duration, a greater inflammatory process and more high resolution computed tomography airway abnormalities suggestive of airway remodelling, despite being on similar treatments and experiencing equivalent impairment in quality of life.
Proteasome inhibitors modulate chemokine production in lung epithelial and monocytic cells
Authors: Gerber A. , Heimburg A. , Reisenauer A. , Wille A. , Welte T. , Bühling F. 
Published: July 2004

Proteasome inhibition has become a target for antitumour and anti-inflammatory therapy. The present study investigated the influence of cysteine proteinase and proteasome inhibitors on chemokine production in lung epithelial cells and monocytic cells.The lung carcinoma cell lines A549, SK‐MES, NCI‐H727, virus-transformed bronchial epithelial cell line BEAS‐2B, primary lung epithelial cells, and the acute monocytic leukaemia cell lines Mono-Mac‐6 and THP‐1 were incubated with proteasome (N‐acetyl‐L‐leucyl‐L‐leucyl‐L‐norleucinal (ALLN), β‐lactone) or cysteine proteinase inhibitor (L‐trans-Epoxysuccinyl-Leu‐3‐methylbutylamide-ethyl ester) and the influence on chemokine production (interleukin‐8: IL‐8, monocyte chemoattractant protein‐1, RANTES) was quantified at protein and mRNA levels.Inhibition of proteasome activity by ALLN and β‐lactone resulted in significantly increased IL‐8 secretion (5‐ to 22‐fold). Cysteine proteinase inhibitors did not influence chemokine production. The simultaneous rise in IL‐8 mRNA was caused by an increased half-life of mRNA and increased RNA synthesis. Moreover, analysis of transcription factor activation revealed induction of activator protein‐1 (c‐Jun) activity by proteasome inhibition, whereas nuclear factor‐κB (p50 and p65) was not activated. The significant increase in IL‐8 production after proteasome inhibition was also observed in primary lung epithelial cells and in monocytic cells. In addition, the secreted IL‐8 was biologically active as shown by the neutrophil chemotaxis assay.In conclusion, it was shown that proteasome inhibitors stimulate interleukin‐8 secretion in lung epithelial cells and monocytic cells, thus recruiting neutrophils.
Relevance of assessing quadriceps endurance in patients with COPD
Authors: Coronell C. , Orozco‐Levi M. , Méndez R. , Ramírez‐Sarmiento A. , Gáldiz J.B. , Gea J. 
Published: July 2004

The aims of this study were to investigate whether the impairment in endurance of limb muscles is a general finding in chronic obstructive pulmonary disease (COPD) patients, affecting even those with mild-to-moderate disease or relatively normal physical activity. In addition, this study aimed to determine the physiopathology of exhaustion in local endurance tests and whether the reduction in quadriceps endurance can be predicted from muscle strength measurements.A total of 75 volunteers were assigned to one of two groups according to pulmonary function tests: COPD patients or healthy age-matched controls. Functional assessment included both quadriceps strength (maximum voluntary contraction (QMVC)), and quadriceps endurance (contractions against a load equivalent to 10% QMVCuntil task failure or for up to a limiting time of 30 min (QTlim)).COPD patients showed a decrease of ∼43% in QMVCand ∼77% in QTlimcompared with controls. Task failure occurred only in COPD patients and was due to muscle fatigue, since limiting symptoms were associated with a decrease in the median frequency of quadriceps electromyographical signal and a reversible decrease in QMVC. The impairment in skeletal muscle endurance was present even in patients with mild-to-moderate airflow obstruction and individuals with relatively normal physical activity, and was irrespective of lung function variables, anthropometrical data or quadriceps strength.Peripheral muscle endurance was impaired in chronic obstructive pulmonary disease patients, even in those with relatively normal physical activity and mild-to-moderate airflow obstruction. This impairment associated with an early onset of muscle fatigue and could not be predicted from the severity of the disease or the reduction in quadriceps strength.
STAT4 activation in smokers and patients with chronic obstructive pulmonary disease
Authors: Di Stefano A. , Caramori G. , Capelli A. , Gnemmi I. , Ricciardolo F.L. , Oates T. , Donner C.F. , Chung K.F. , Barnes P.J. , Adcock I.M. 
Published: July 2004

Activation of the transcription factor signal transducer and activator of transcription (STAT)‐4 is critical for the differentiation of T‐helper 1 cells/type‐1 cytotoxic T‐cells and the production of interferon (IFN)‐γ.Expression of STAT4, phospho‐STAT4, IFN‐γ and T‐box expressed in T‐cells (T‐bet) proteins in bronchial biopsies and bronchoalveolar lavage (BAL)‐derived lymphocytes, obtained from 12 smokers with mild/moderate chronic obstructive pulmonary disease (COPD) (forced expiratory volume in one second (FEV1) 59±16% predicted), 14 smokers with normal lung function (FEV1106±12% pred) and 12 nonsmoking subjects (FEV1111±14% pred), was examined by immunohistochemistry and immunocytochemistry.In bronchial biopsies of COPD patients, the number of submucosal phospho‐STAT4+ cells was increased (240 (22–406)versus125 (0–492)versus29 (0–511) cells·mm−2) when compared with both healthy smokers and control nonsmokers, respectively. In smokers, phospho‐STAT4+ cells correlated with the degree of airflow obstruction and the number of IFN‐γ+ cells. Similar results were seen in BAL (2.8 (0.2–5.9)versus1.03 (0.09–1.6)versus0.69 (0–2.3) lymphocytes·mL−1×103). In all smokers who underwent lavage, phospho‐STAT4+ lymphocytes correlated with airflow obstruction and the number of IFNγ+ lymphocytes. T‐bet expression was not altered in bronchial biopsies and BAL‐derived lymphocytes between the three groups.In conclusion, this study suggests that stable mild/moderate chronic obstructive pulmonary disease is associated with an active T‐helper 1 cell/type‐1 cytotoxic T‐cell inflammatory process involving activation of signal transducer and activator of transcription 4 and interferon-gamma production.
Area deprivation predicts lung function independently of education and social class
Authors: Shohaimi S. , Welch A. , Bingham S. , Luben R. , Day N. , Wareham N. , Khaw K‐T. 
Published: July 2004

The cross-sectional association between socioeconomic status (at both the individual and area-based level) and lung function, as measured by forced expiratory volume in one second, in a large population-based cohort was investigated.The study population consisted of 22,675 males and females aged 39–79 yrs. They were recruited from the general community in Norfolk, UK using general practice age/sex registers, as part of the European Prospective Investigation into Cancer (EPIC-Norfolk).It was found that being in a manual occupational social class, having no educational qualifications and living in a deprived area all independently predicted significantly lower lung function, even after controlling for smoking habit.The influence of area-deprivation on lung function, independent of individual socioeconomic status and of individual smoking habit, suggests that apart from targeting individuals who are at high-risk, such as smokers, environmental determinants also need to be examined when considering measures to improve respiratory health.
Tuberculosis in HIV‐infected persons in the context of wide availability of highly active antiretroviral therapy
Authors: Girardi E. , Antonucci G. , Vanacore P. , Palmieri F. , Matteelli A. , Iemoli E. , Carradori S. , Salassa B. , Bruna Pasticci M. , Raviglione M.C. , Ippolito G. ,   the GISTA-SIMIT Study Group
Published: July 2004

Highly active antiretroviral therapy (HAART) greatly reduces the risk of developing tuberculosis for HIV‐infected persons. Nonetheless, HIV‐associated tuberculosis continues to occur in countries where HAART is widely used.To identify the characteristics of HIV‐infected persons who develop tuberculosis in the context of the availability of HAART, the current authors analysed data taken from 271 patients diagnosed, in Italy, during 1999–2000. These patients represent 0.7% of the 40,413 HIV‐infected patients cared for in the clinical units participating in this current study.From the data it was observed that 20 patients (7.4%) had a previous episode of tuberculosis whose treatment was not completed. Eighty-one patients (29.9%) were diagnosed with HIV at tuberculosis diagnosis, 108 (39.8%) were aware of their HIV status but were not on antiretroviral treatment and 82 (30.3%) were on antiretroviral treatment. Patients on antiretroviral treatment were significantly less immunosuppressed than patients with HIV diagnosed concurrently with tuberculosis, or other patients not on antiretrovirals (median CD4 lymphocytes count: 220 cells·mm−3versus100 cells·mm−3, and 109 cells·mm−3, respectively). No significant differences in clinical presentation of tuberculosis according to antiretroviral therapy status were recorded.Failure of tuberculosis control interventions (e.g.noncompletion of treatment) and of HIV care (delayed diagnosis of HIV infection and suboptimal uptake of therapy) may contribute to continuing occurrence of HIV‐associated tuberculosis in a country where highly active antiretroviral therapy is largely available. However, a significant proportion of cases occur in patients who are on antiretroviral treatment.
CCL22 and CCL17 in rat radiation pneumonitis and in human idiopathic pulmonary fibrosis
Authors: Inoue T. , Fujishima S. , Ikeda E. , Yoshie O. , Tsukamoto N. , Aiso S. , Aikawa N. , Kubo A. , Matsushima K. , Yamaguchi K. 
Published: July 2004

Pulmonary fibrosis is caused by various known and unknown aetiologies, but the key pathogenic mechanisms are still ill-defined. Chemokines are a large family of chemotactic cytokines that play pivotal roles in various inflammatory diseases.In the present study, the roles of chemokines in a rat model of radiation pneumonitis/pulmonary fibrosis were examined.Accumulation of inflammatory cells and pneumonitis were observed on day 28, and diffuse alveolar wall thickening with extensive fibrosis was observed on day 56. In addition to the previously reported CCL2 (macrophage chemoattractant protein‐1) induction, selective upregulation of CCL22 (macrophage-derived chemokine) and CCL17 (thymus and activation-regulated chemokine) were demonstrated for the first time in the irradiated lung tissues. Immunohistochemically, it was demonstrated that CCL22 and CCL17 were localised primarily to alveolar macrophages, whereas their receptor CC chemokine receptor 4 (CCR4) was detected on alveolar lymphocytes and macrophages. On further analysis of bronchoalveolar lavage fluid from patients with idiopathic pulmonary fibrosis and sarcoidosis, elevated levels of CCL22, but not of CCL17, were observed in the idiopathic pulmonary fibrosis patients.Since these two chemokines play pivotal roles in various type‐2 T‐helper cell-dominant diseases, it was speculated that CCL22, and probably CCL17, are involved in the pathophysiology of radiation pneumonitis/pulmonary fibrosis and idiopathic pulmonary fibrosis through the recruitment of CC chemokine receptor 4‐positive type‐2 T‐helper cells and alveolar macrophages.
Pirfenidone attenuates expression of HSP47 in murine bleomycin-induced pulmonary fibrosis
Authors: Kakugawa T. , Mukae H. , Hayashi T. , Ishii H. , Abe K. , Fujii T. , Oku H. , Miyazaki M. , Kadota J. , Kohno S. 
Published: July 2004

Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagen. The present study was undertaken to investigate whether treatment with the antifibrotic drug pirfenidone attenuates the bleomycin (BL)‐induced overexpression of HSP47 in the lungs.Male ICR mice were intravenously injected with BL or saline (SA). Pirfenidone or control drug (CD) was administered 14 days after commencement of BL or SA, and continued throughout the course of the experiment. The mice were randomly divided into three experimental groups: 1) SA‐treated with CD (SA group); 2) BL‐treated with CD (BL group); and 3) BL‐treated with pirfenidone (pirfenidone group).Lungs of the pirfenidone group showed a marked reduction of fibrotic lesions compared with the corresponding BL group. Immunohistochemical studies showed that BL treatment significantly increased the number of macrophages, myofibroblasts, HSP47‐positive type II pneumocytes and HSP47‐positive interstitial spindle-shaped cells. Treatment with pirfenidone significantly reduced the number of these cells compared with the corresponding BL group. Furthermore, treatment with pirfenidone significantly suppressed the BL‐induced increase of the positive ratio of HSP47 and α‐smooth muscle actin to interstitial spindle-shaped cells.The present study results showed that pirfenidone inhibited heat shock protein 47‐positive cells and myofibroblasts, the principal cells responsible for the accumulation and deposition of extracellular matrix seen in pulmonary fibrosis.
Atypical pathogens and respiratory tract infections
Authors: Blasi F. 
Published: July 2004

The atypical respiratory pathogensChlamydia pneumoniae,Mycoplasma pneumoniaeandLegionella pneumophilaare now recognised as a significant cause of acute respiratory-tract infections, implicated in community-acquired pneumonia, acute exacerbations of chronic bronchitis, asthma, and less frequently, upper respiratory-tract infections.Chronic infection withC. pneumoniaeis common among patients with chronic obstructive pulmonary disease and may also play a role in the natural history of asthma, including exacerbations. The lack of a gold standard for diagnosis of these pathogens still handicaps the current understanding of their true prevalence and role in the pathogenesis of acute and chronic respiratory infections.While molecular diagnostic techniques, such as polymerase chain reaction, offer improvements in sensitivity, specificity and rapidity over culture and serology, the need remains for a consistent and reproducible diagnostic technique, available to all microbiology laboratories.Current treatment guidelines for community-acquired pneumonia recognise the importance of atypical respiratory pathogens in its aetiology, for which macrolides are considered suitable first-line agents. The value of atypical coverage in antibiotic therapy for acute exacerbations of chronic bronchitis and exacerbations of asthma is less clear, while there is no evidence to suggest that atypical pathogens should be covered in antibiotic treatment of upper respiratory-tract infections.
Acute effect of oral steroids on muscle function in chronic obstructive pulmonary disease
Authors: Hopkinson N.S. , Man W.D‐C. , Dayer M.J. , Ross E.T. , Nickol A.H. , Hart N. , Moxham J. , Polkey M.I. 
Published: July 2004

Prospective data to support the hypothesis that corticosteroids are a significant cause of muscle weakness in patients with chronic obstructive pulmonary disease (COPD) are lacking.The authors studied respiratory and quadriceps muscle function, using both volitional techniques and magnetic nerve stimulation, as well as measuring metabolic parameters during incremental cycle ergometry, in 25 stable COPD patients. The forced expiratory volume in one second was 37.6±21.4 % predicted, before and after a 2‐week course ofo.d.prednisolone 30 mg. Quadriceps strength was also assessed in 15 control patients on two occasions.Only two patients met the British Thoracic Society definition of steroid responsiveness. There was no change either in sniff transdiaphragmatic pressure (pre: 96.8±19.7 cmH2O; post: 98.6±22.4 cmH2O) or in twitch transdiaphragmatic pressure elicited by bilateral anterolateral magnetic phrenic-nerve stimulation (pre: 16.8±9.1 cmH2O; post: 17.9±10 cmH2O). Quadriceps twitch force did not change significantly either in the steroid group (pre: 9.5±3.1 kg; post: 8.9±3.7 kg) or in the control patients (pre: 8.1±2.7 kg; post: 7.9±2.2 kg). There were no changes in either peak or isotime ventilatory and metabolic parameters during exercise.In conclusion, in stable patients with chronic obstructive pulmonary disease, a 2‐week course of 30 mg prednisolone daily does not cause significant skeletal muscle dysfunction or alter metabolic parameters during exercise.
Predictors of antipsychotic treatment response in patients with first-episode schizophrenia, schizoaffective and schizophreniform disorders
Authors: Perkins Diana O. , Lieberman Jeffrey A. , Gu Hongbin , Tohen Mauricio , McEvoy Joseph , Green Alan I. , Zipursky Robert B. , Strakowski Stephen M. , Sharma Tonmoy , Kahn René S. , Gur Raquel , Tollefson Gary 
Published: June 2004

BackgroundDuration of untreated psychosis (DUP) may contribute to the observed heterogeneity of the treatment response in first-episode schizophrenia.AimsTo examine the relationship of DUP and premorbid function with clinical outcomes following up to 2 years of antipsychotic treatment.MethodFor a subsample (n= 191) of subjects participating in a clinical trial, DUP and premorbid function were prospectively compared with clinical response to olanzapine or haloperidol.ResultsShorter DUP and good premorbid function each independently are associated with better clinical response, including improvement in overall psychopathology and negative symptoms. Premorbid function also is associated with positive symptom, social and vocational outcomes.ConclusionsEarlier antipsychotic treatment is associated with better outcomes in first-episode schizophrenia. Poor premorbid function could indicate an illness subtype less likely to respond to antipsychotic treatment regardless of when it is instituted.
Consultant psychiatrists' working patterns: is a progressive approach the key to staff retention?
Authors: Mears Alex , Pajak Sarah , Kendall Tim , Katona Cornelius , Medina Jibby , Huxley Peter , Evans Sherrill , Gately Claire 
Published: June 2004

Aims and MethodThe aim of the study was to explore how different styles of working relate to measures of occupational pressure experienced by consultant psychiatrists. A questionnaire was sent to a random sample of 500 consultant psychiatrists enquiring about work patterns, roles and responsibilities; it also contained validated tools, including the 12-item General Health Questionnaire.ResultsA total of 185 usable questionnaires were returned; an adjusted response rate of 41%. More ‘progressive’ styles of working were found to be linked with less occupational pressure on consultant psychiatrists. Three scales were derived: positive workload pattern, clarity of role and perceived support.Clinical ImplicationsAlterations in working style may be helpful in combating occupational stress, and therefore in reducing attrition in the psychiatric workforce. Consultants and their teams should give consideration to reviewing their roles and patterns of working.
Attitudes and emotions of trainees in learning disability psychiatry
Authors: Graham Simon , Herbert Rosemary , Price Sarah , Williams Shan 
Published: July 2004

Aims and MethodWe aimed to formally examine the attitudes and emotions engendered in a group of senior house officers (SHOs) working in learning disability, by means of focus groups held both during and immediately after placement. Three hour-long focus group sessions, facilitated by a consultant psychotherapist, were recorded on audio- and video-tape. Transcripts of the audiotapes were examined in order to identify themes and categorise them in terms of attitudes, behaviours and emotions.ResultsMany of the thoughts, feelings and behaviours identified showed negative themes originating from the trainees, particularly towards themselves and patients. The trainees only twice perceived themselves to be the recipients of any positive themes.Clinical ImplicationsAddressing these negative experiences as a potential problem might enrich and enhance trainees' experiences of their learning disability placements. A Balint group could be a starting point for this. If the problem were addressed, recruitment to and retention within the specialty might improve.