bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bronchodilator tolerance: the impact of increasing bronchoconstriction
Authors: Wraight J.M. , Hancox R.J. , Herbison G.P. , Cowan J.O. , Flannery E.M. , Taylor D.R. 
Published: May 2003

Chronic exposure to β‐agonists causes tolerance to their bronchodilator effects, which is best demonstrated during acute bronchoconstriction. The aim of the present study was to assess whether tolerance becomes more evident with increasing bronchoconstriction, as might occur in acute asthma.In a randomised, double-blind, placebo-controlled, crossover study comprising 15 patients, the treatments were salbutamol 400 µgq.i.d. or placebo givenviaDiskhaler® for 28 days with a 2‐week washout between treatments. Patients attended on days 14, 21 and 28. Bronchoconstriction was induced on two of these three occasions to achieve a reduction in the forced expiratory volume in one second (FEV1) of 0 (no methacholine), 15 and 30% (using methacholine) in a randomised order. Immediately after this, salbutamol 100 µg, 100 µg and 200 µg was inhaled at 0, 5, and 10 min. FEV1was measured over 40 min. Dose/response curves were plotted and values for the area under the curve (AUC)0–40FEV1were compared between treatments and by degree of bronchoconstriction.Regular salbutamol resulted in attenuation of the acute response to β‐agonist, which was increasingly evident with greater bronchoconstriction. With a reduction in FEV1of 0, 15 and 30%, the AUC0–40FEV1with salbutamol were 11.2, −14.6 and −35.7% respectively, compared to placebo. There was a linear relationship between the magnitude of bronchoconstriction and the between-treatment differences in AUC0–40FEV1.Increasing bronchoconstriction conferred greater susceptibility to the effects of bronchodilator tolerance.
Rigid bronchoscopy induces bacterial translocation: an experimental study in rats
Authors: Nayci A. , Atis S. , Talas D.U. , Ersoz G. 
Published: May 2003

Bronchoscopy has the potential to propagate infections. Bacterial translocation was hypothesised to be the cause of infections observed following bronchoscopy and this study was designed to assess the risk of bacterial translocation following rigid bronchoscopy in rats.A total of 30 rats were evaluated. The study group (n=15) underwent rigid bronchoscopy. Arterial blood gas analysis was performed in all rats. Blood and tissue cultures from the ileum, caecum, mesenteric lymph nodes, liver, spleen, mediastinal lymph nodes and lung were obtained 24 h following bronchoscopy.Bacterial translocation to the mesenteric lymph nodes was found in seven of 15 rats (46.7%) that underwent bronchoscopy, compared with none of the controls. Of the seven positives, three rats (42.8%) also demonstrated other organ involvement, such as the liver and spleen.Escherichia coli,Salmonella typhymirium,S. enteritidisandPseudomonasspp. were found as translocating bacteria. In the study group, pH and arterial oxygen tension were significantly lower and arterial carbon dioxide tension was higher, compared with controls.This study shows that rigid bronchoscopy may induce bacterial translocation in rats. Further investigations aimed at understanding the clinical consequences of this phenomenon are warranted.
Dexamethasone treatment does not inhibit fibroproliferation in chronic lung disease of prematurity
Authors: Dik W.A. , Versnel M.A. , Naber B.A. , Janssen D.J. , van Kaam A.H. , Zimmermann L.J.I. 
Published: May 2003

Pulmonary fibrosis results from excessive fibroblast proliferation and increased collagen deposition and occurs in chronic lung disease of prematurity (CLD). Platelet-derived growth factor (PDGF)-BB is mitogenic for fibroblasts and levels are increased in fibrotic lung disorders. Systemic dexamethasone (DEX) treatment improves pulmonary function and reduces inflammation in infants with or at risk of CLD. However, the effect of DEX treatment on fibroblast activity, PDGF-BB and collagen synthesis in the lungs of CLD patients is uncertain.Bronchoalveolar lavage (BAL) fluids, obtained from 15 infants at risk of CLD before and after DEX treatment, were analysed for fibroblast mitogenicity, PDGF-BB, N‐terminal propeptide of collagen type III (PIIINP) and interleukin (IL)-1β levels and inflammatory cell numbers.After DEX treatment, the mitogenic activity of BAL fluid for fibroblasts was not reduced but increased. The change in mitogenicity correlated with a change in BAL fluid PDGF-BB levels. Furthermore, BAL fluid-induced fibroblast proliferation was blocked using an inhibitor of the PDGF receptor. DEX treatment did not influence PIIINP levels, but reduced IL-1β levels and inflammatory cell numbers in BAL fluid.This study suggests that dexamethasone treatment does not reduce fibroblast proliferation despite apparent downregulation of inflammation. The present findings do not support the use of dexamethasone for prevention of the fibrotic response in infants at risk of chronic lung disease of prematurity.
Transcription factor activation and mitogenic synergism in airway smooth muscle cells
Authors: Ediger T.L. , Schulte N.A. , Murphy T.J. , Toews M.L. 
Published: May 2003

Simultaneous treatment of human airway smooth muscle (HASM) cells with lysophosphatidic acid (LPA) and epidermal growth factor (EGF) leads to strikingly synergistic stimulation of mitogenesis. The purpose of this study was to explore potential sites for signal integration mediating synergism, focusing on extracellular signal-regulated kinase (ERK) and transcription factors involved in proliferation and inflammation as likely candidates.Activation of ERK was analysed by immunoblotting. Transcription factor activation was assessed using HASM cells transduced with luciferase reporter gene constructs.LPA and EGF both activated ERK but had no synergistic effect when combined. LPA and EGF both activated activator protein (AP)‐1, cyclic adenosine monophosphate response element-binding protein, nuclear factor of activated T‐cells and the serum response element; however, only AP‐1 activation exhibited synergism. Activation of the inhibitory guanine nucleotide-binding protein and of ERK signalling pathways were required for most transcription factor responses to LPA. In contrast, nuclear factor (NF)‐κB was activated by LPA but not EGF and NF‐κB activation was completely blocked only when Rho was inhibited. Rapid activation of Rho was observed in response to LPA but not to EGF. Importantly, inhibition of Rho selectively blocked synergism in both AP‐1 activation and mitogenesis.In summary, extracellular signal-regulated kinase activation is required for many transcription factor responses to lysophosphatidic acid and epidermal growth factor, however it is not synergistic. Activation of activator protein‐1 is synergistic, and Rho activation by lysophosphatidic acid is required for synergism in both activator protein‐1 activation and mitogenesis.
The role of adherence in tuberculosis HIV‐positive patients treated in ambulatory regimen
Authors: Rocha M. , Pereira S. , Ferreira L. , Barros H. 
Published: May 2003

Adherence to antituberculosis treatment, a major determinant of outcome, is of special concern in human immunodeficiency virus (HIV)‐positive patients. However, tuberculosis death in HIV‐positive patients remains higher than in HIV‐negative patients, regardless of adherence.To assess determinants for an unfavourable tuberculosis outcome (defined as no cure or death), and determinants for nonadherence to antituberculosis treatment, 70 HIV‐positive patients with tuberculosis referred to an outpatient centre were studied. Patient outcome was compared according to HIV risk factors, other opportunistic diseases, antiretroviral drugs use, currenti.v.drugs use, a methadone programme participation, tuberculosis features, treatment characteristics and adherence. Adherent and nonadherent patient characteristics were also compared.An unfavourable outcome occurred in 22.9% of patients and 32.9% were nonadherent with therapy. Nonadherence was the only independent determinant for an unfavourable outcome. Adherence was independently associated with currenti.v.drug use, treatment complications and use of methadone.This study confirms that human immunodeficiency virus-infected patients, treated as outpatients, have high rates of nonadherence and that adherence is the strongest determinant for tuberculosis outcome. Independently of the current use of drugs, a methadone programme improves adherence to treatment.
Increased immunoreactivity of stromal cell-derived factor‐1 and angiogenesis in asthma
Authors: Hoshino M. , Aoike N. , Takahashi M. , Nakamura Y. , Nakagawa T. 
Published: May 2003

Stromal cell-derived factor‐1 (SDF‐1) acts as a chemoattractant for leukocytes and can induce neovascularisation. To examine the role of SDF‐1 in the development of angiogenesis, immunohistochemical studies were performed on bronchial biopsy specimens from asthmatic and control subjects.Bronchial biopsy specimens were obtained from 13 asthmatic and eight control subjects. The number of vessels and the percentage area they occupied were estimated after staining for type‐IV collagen. In addition the number of SDF‐1‐positive cells was determined.There was a significant increase in the number of vessels and the percentage vascularity in the submucosa of asthmatic subjects compared with control subjects. Asthmatic subjects exhibited a greater number of SDF‐1‐positive cells in the airway mucosa than control subjects. The degree of vascularity was associated with the number of SDF‐1‐positive cells. Furthermore, the number of SDF‐1‐positive cells was inversely correlated with airway calibre and airway hyperresponsiveness. Colocalisation studies revealed that endothelial cells, macrophages and T‐lymphocytes were the major sources of SDF‐1.These findings suggest that increased vascularity of bronchial mucosa in asthmatic subjects is closely related to the expression of stromal cell-derived factor‐1 positive cells, which may play a role in remodelling of airwaysviaangiogenesis.
Dehydroepiandrosterone sulphate reduces chronic hypoxic pulmonary hypertension in rats
Authors: Hampl V. , Bíbová J. , Povýšilová V. , Herget J. 
Published: May 2003

Pathogenesis of pulmonary hypertension includes vascular smooth muscle cell membrane depolarisation and consequent calcium influx. Usually, calcium-gated potassium channels are activated under such conditions and repolarise the membrane. However, in pulmonary hypertension they are downregulated. The authors hypothesised that pharmacological augmentation of these channels would reduce pulmonary hypertension.Dehydroepiandrosterone sulphate (DHEA‐S, 0.1 mg·mL−1), a recently characterised activator of calcium-gated potassium channels, was given to rats in drinking water.Pulmonary arterial blood pressure, increased by 4 weeks of hypoxia (from 15±0.2 to 29.4±2.5 mmHg), was selectively attenuated in rats treated with DHEA‐S for the whole duration of the hypoxic exposure (23.9±0.9 mmHg) and in rats given DHEA‐S only after pulmonary hypertension had fully developed (last 2 weeks of hypoxia; 24.4±1.4 mmHg). Pulmonary vascular remodelling and right ventricular hypertrophy associated with pulmonary hypertension were also reduced by DHEA‐S. Cardiac index and systemic arterial blood pressure did not differ among the groups.The authors conclude that treatment with an activator of calcium-gated potassium channels, dehydroepiandrosterone sulphate, known to be well tolerated by humans, reduces hypoxic pulmonary hypertension in rats.
Increased vascular endothelial growth factor in acute eosinophilic pneumonia
Authors: Nishigaki Y. , Fujiuchi S. , Yamazaki Y. , Matsumoto H. , Takeda A. , Fujita Y. , Okamoto K. , Fujikane T. , Shimizu T. , Kikuchi K. 
Published: May 2003

Acute eosinophilic pneumonia (AEP) is associated with the presence of diffuse pulmonary infiltrates on the chest radiograph and an increased number of eosinophils and an elevation of interleukin (IL)‐5 levels in bronchoalveolar lavage (BAL) fluid. Vascular endothelial growth factor (VEGF) is a constitutively expressed protein encoded by messenger ribonucleic acid in human eosinophils and is released following stimulation with IL‐5. However, the roles of IL‐5 and VEGF in the pathogenesis or activity of this disease have not been clarified.The authors investigated the cells and the levels of these two factors in BAL fluid in five AEP patients and five normal controls before and after corticosteroid treatment.The absolute number of eosinophils·mL−1, IL‐5 and VEGF levels in patients before treatment were higher than in controls (53.8versus0.3×104·mL−1, 490.1versus5.2 pg·mL−1and 643.0versus133.9 pg·mL−1, respectively). IL‐5 and VEGF rapidly decreased to the control level in parallel with clinical improvement. The relationship between eosinophilia and IL‐5 and VEGF levels was strongly significant.Elevated interleukin‐5 in the lung may initiate the recruitment of eosinophils and enhance the release of mediators, such as vascular endothelial growth factor from eosinophils, which, in turn, increases the permeability of blood vessels.
Fragile histidine triad protein expression in nonsmall cell lung cancer and correlation with Ki-67 and with p53
Authors: Mascaux C. , Martin B. , Verdebout J.M. , Meert A.P. , Ninane V. , Sculier J.P. 
Published: May 2003

Fragile histidine triad (FHIT) is a tumour suppressor gene, which is altered in a variety of epithelial tumours, including lung cancer. Biochemical and functional pathways of its tumourigenicity are not yet understood. Its role in tumour proliferation is particularly controversial. The purpose of this study was to correlate the expression of FHIT protein in nonsmall cell lung cancer (NSCLC) with tumour proliferation as estimated by Ki-67 antigen and with p53, a suppressor gene.FHIT, Ki-67 and p53 expression were evaluated by immunohistochemistry in 119 resected NSCLC.Altogether, 58 tumours were negative (expression <10%) for FHIT. The median expression in tumours was 15% positive cells, in comparison with 100% in normal matched lung tissue. The expression was as strong as in normal tissue in only 19 cases. FHIT expression was significantly lower in squamous cell carcinoma (SCC) (5%) than in adenocarcinoma (ADC) (64%). The median expression of Ki-67 was 20% and 69% of tumours were positives (expression >10%). Ki-67 expression was significantly higher in SCC (33.3%) than in ADC (10%). The loss of FHIT protein was not correlated with the expression of p53 (median: 7.5%, 58% of positive tumours for a cut-off of 10% of positive cells) or Ki-67. But percentage of labelled cells for p53 and Ki-67 were significantly correlated.The results suggest that for fragile histidine triad, the pathway of tumourigenesis is independent of p53 and of tumoural proliferation, as reported previouslyin vitro.
Chlamydiaspecies as a cause of community-acquired pneumonia in Canada
Authors: Marrie T.J. , Peeling R.W. , Reid T. , De Carolis E. ,   the Canadian Community-Acquired Pneumonia Investigators
Published: May 2003

Chlamydia pneumoniaehas been implicated as a cause of community-acquired pneumonia (CAP) in several studies. However, there has been no comprehensive study of the role ofChlamydiaspecies (C. pneumoniae,C. psittaci(avian and feline strains) andC. pecorum) as a cause of CAP. The aim of the present study was to determine the role ofC. pneumoniae,C. psittaciandC. pecorumas causes of CAP.A prospective cohort observational study of CAP was conducted at 15 teaching centres in eight Canadian provinces between January 1996–October 1997. Acute (n=539) and convalescent (n=272) serum samples were obtained for determination of antibody titres toC. pneumoniae,C. psittaci,C. pecorum,C. trachomatis,Mycoplasma pneumoniae,Legionella pneumophilaserogroups I–VI,Streptococcus pneumoniaeand various respiratory viruses.Twelve of 539 (2.2%) patients had acuteC. pneumoniaepneumonia and an additional 32 (5.9%) had possible acute infection.C. pneumoniaewas the sole pathogen in 16 of 42 (38.1%) of these patients. The most common copathogens wereS. pneumoniae, respiratory syncytial virus and influenza virus type A.C. pneumoniaepneumonia patients were older and more likely to show congestive heart failure compared to bacteraemicS. pneumoniaepatients. The latter had a lower mean diastolic blood pressure, a higher white blood cell count and a lower arterial carbon dioxide tension. Two patients had antibody titres suggestive of recent infection with the feline strain ofC. psittaci.Although numericallyChlamydia pneumoniaeis an important cause of community-acquired pneumonia, no distinctive clinical features associated with this pathogen were detected in the present study. FelineChlamydia psittacimay cause a few cases of community-acquired pneumonia. AvianChlamydia psittacishould be considered only if there is a compatible epidemiological history.
Pulmonary hypertension in chronic obstructive pulmonary disease
Authors: Barberà J.A. , Peinado V.I. , Santos S. 
Published: May 2003

Pulmonary hypertension is a common complication of chronic obstructive pulmonary disease (COPD). Its presence is associated with shorter survival and worse clinical evolution. In COPD, pulmonary hypertension tends to be of moderate severity and progresses slowly. However, transitory increases of pulmonary artery pressure may occur during exacerbations, exercise and sleep. Right ventricular function is only mildly impaired with preservation of the cardiac output.Structural and functional changes of pulmonary circulation are apparent at the initial stages of COPD. Recent investigations have shown endothelial dysfunction and changes in the expression of endothelium-derived mediators that regulate vascular tone and cell growth in the pulmonary arteries of patients with mild disease. Some of these changes are also present in smokers with normal lung function. Accordingly, it has been postulated that the initial event in the natural history of pulmonary hypertension in COPD could be the lesion of pulmonary endothelium by cigarette-smoke products.Long-term oxygen administration is the only treatment that slows down the progression of pulmonary hypertension in chronic obstructive pulmonary disease. Nevertheless, with this treatment pulmonary artery pressure rarely returns to normal values and the structural abnormalities of pulmonary vessels remain unaltered. Vasodilators are not recommended on the basis of their minimal clinical efficacy and because they impair pulmonary gas exchange. Recognition of the role of endothelial dysfunction in the physiopathology of pulmonary hypertension in chronic obstructive pulmonary disease opens new perspectives for the treatment of this complication.
Increased eNO and pulmonary iNOS expression in eNOS null mice
Authors: Cook S. , Vollenweider P. , Ménard B. , Egli M. , Nicod P. , Scherrer U. 
Published: May 2003

Nitric oxide (NO) is a major regulatory molecule of the cardiovascular system; however, measurement of vascular NO synthesisin vivorepresents a major challenge. NO stemming from the lower respiratory tract has been used as a marker of vascular endothelial function. Experimental evidence for this concept is lacking. Therefore, the aim of the present study was to investigate this relationship.Lower respiratory tract exhaled NO concentration, together with systemic and pulmonary artery pressure, was measured in endothelial nitric oxide synthase (NOS) (eNOS) null mice (eNOS-/-). Similar studies were performed in inducible NOS (iNOS) null mice (iNOS-/-).Defective endothelial NO synthesis in eNOS-/- mice (evidenced by systemic and pulmonary hypertension) was associated with augmented exhaled NO levels (12.5±1.9versus9.8±1.2 parts per billion (ppb), eNOS-/-versuswild type), whereas normal endothelial NO synthesis in iNOS-/- mice was associated with decreased exhaled NO levels (4.3±1.5 ppb). Augmented exhaled NO levels in eNOS-/- mice were associated with upregulation of iNOS expression in the lung.These results indicate that inducible nitric oxide synthase is a major determinant of gaseous nitric oxide production in the lung, and lower respiratory tract exhaled nitric oxide does not always represent a marker of vascular endothelial nitric oxide synthesis.
Tidal expiratory flow limitation, dyspnoea and exercise capacity in patients with bilateral bronchiectasis
Authors: Koulouris N.G. , Retsou S. , Kosmas E. , Dimakou K. , Malagari K. , Mantzikopoulos G. , Koutsoukou A. , Milic-Emili J. , Jordanoglou J. 
Published: May 2003

In this study the authors investigated whether expiratory flow limitation (FL) is present during tidal breathing in patients with bilateral bronchiectasis (BB) and whether it is related to the severity of chronic dyspnoea (Medical Research Council (MRC) dyspnoea scale), exercise capacity (maximal mechanical power output (WRmax)) and severity of the disease, as assessed by high-resolution computed tomography (HRCT) scoring.Lung function, MRC dyspnoea, HRCT score,WRmaxand FL were assessed in 23 stable caucasian patients (six males) aged 56±17 yrs. FL was assessed at rest both in seated and supine positions. To detect FL, the negative expiratory pressure (NEP) technique was used. The degree of FL was rated using a five-point FL score.WRmaxwas measured using a cyclo-ergometer.According to the NEP technique, five patients were FL during resting breathing when supine but not seated, four were FL both seated and supine, and 14 were NFL both seated and supine. Furthermore, it was shown that: 1) in stable BB patients FL during resting breathing is common, especially in the supine position; 2) the degree of MRC dyspnoea is closely related to the five-point FL score; 3)WRmax(% pred) is more closely correlated with the MRC dyspnoea score than with the five-point FL score; and 4) HRCT score is closely related to forced expiratory volume in one second % pred but not five-point FL score.In conclusion, flow limitation is common at rest in sitting and supine positions in patients with bilateral bronchiectasis. Flow limitation and reduced exercise capacity are both associated with more severe dyspnoea. Finally, high-resolution computed tomography scoring correlates best with forced expiratory volume in one second.
Risk factors for death rattle in terminally ill cancer patients: a prospective exploratory study
Authors: Morita Tatsuya , Tsunoda Junichi , Inoue Satoshi , Chihara Satoshi 
Published: May 2003

Death rattle is frequently observed in cancer patients whose death is impending and may contribute to the severe distress of patients and their family members. To identify risk factors for development and persistency of death rattle, a prospective study was performed on 245 hospice inpatients. One-hundred-and-seven patients (44%) developed death rattle, 71% of whom achieved satisfactory symptom palliation until death. A multiple regression analysis identified neoplasms of brain and lung as independent risk factors for development of death rattle, while refractory symptoms were significantly associated with pulmonary neoplasms and infection/oedema. In conclusion, development of death rattle was influenced by both brain and lung malignancies, while its persistency was mainly determined by pulmonary pathology. A clinical classification of death rattle based on these factors would be established by a further confirmatory study.