bluuebunny/crossref_metadata_2025 huggingface dataset:
El sesgo lingüístico intergrupal: el efecto de la valencia de las categorías lingüísticas
Authors: Valencia Jose , de Montes Lorena Gil , Arruti Itziar , Carbonell Arantxa
Published: January 2003

El nivel de abstracción del lenguaje puede ser un medio de transmisión y mantenimiento de estereotipos, tal como propone el Sesgo Lingüístico Intergrupal (Maass et al., 1989). En este estudio se analiza el uso diferencial del nivel de abstracción del lenguaje producidopor dos grupos en conflicto (HB y Gesto por la Paz) cuando dan razonamientos referentes a acciones bien congruentes o bien incongruentes con su propio grupo. Mediante un diseño 2 (congruencia de la acción) x 2 (valencia de los verbos utilizados en los razonamientos), se analizará si son los procesos motivacionales o los cognitivos los que llevan a los participantes a una utilización sesgada del lenguaje (Sesgo Lingüístico Intergrupal). Finalmente, los resultados del estudio serán explicados haciendo referencia a las diferentes teorías que en este caso puedan explicar el Sesgo Lingüístico Intergrupal, así como al contexto socio-político en que conviven ambos grupos.
Eosinophilic inflammation in sputum of poorly controlled asthmatics
Authors: Romagnoli M. , Vachier I. , Tarodo de la Fuente P. , Meziane H. , Chavis C. , Bousquet J. , Godard P. , Chanez P.
Published: January 2003

Despite full effective treatment, asthmatic patients often present with poorly controlled asthma. Airway eosinophilia is associated with asthma, but its relationship with asthma control is still undetermined.

To investigate the relationship between airway eosinophilia and asthma control, cellular and biochemical markers of airway inflammation were measured in 19 subjects with poorly controlled asthma, 16 subjects with asthma under control and eight normal volunteers. The severity of asthma was mild-to-moderate persistent in 23 patients (14 poorly controlled) and severe prednisone-dependent in 12 subjects (five poorly controlled). Induced sputum was analysed for total and differential cell counts, leukotriene E4 (LTE4), eosinophil cationic protein (ECP), regulated on activation, normal T-cell expressed and secreted (RANTES), and interleukin (IL)-8.

Sputum eosinophils, LTE4, ECP and RANTES levels (but not IL-8) were significantly higher in patients with poorly controlled asthma as compared to patients with controlled asthma. By contrast, sputum cells and sputum inflammatory markers were not different among groups of patients with different severity of asthma.

These results suggest that sputum eosinophilia is associated with poorly controlled asthma rather than with the severity of asthma.
Physiology and pathophysiology of pleural fluid turnover
Authors: Zocchi L.
Published: January 2003

Tight control of the volume and composition of the pleural liquid is necessary to ensure an efficient mechanical coupling between lung and chest wall. Liquid enters the pleural space through the parietal pleura down a net filtering pressure gradient. Liquid removal is provided by an absorptive pressure gradient through the visceral pleura, by lymphatic drainage through the stomas of the parietal pleura, and by cellular mechanisms. Indeed, contrary to what was believed in the past, pleural mesothelial cells are metabolically active, and possess the cellular features for active transport of solutes, including vesicular transport of protein. Furthermore, the mesothelium was shown, on the basis of recent experimental evidence, bothin vivoandin vitro, to be a less permeable barrier than previously believed, being provided with permeability characteristics similar to those of the microvascular endothelium. Direct assessment of the relative contribution of the different mechanisms of pleural fluid removal is difficult, due to the difficulty in measuring the relevant parameters in the appropriate areas, and to the fragility of the mesothelium. The role of the visceral pleura in pleural fluid removal under physiological conditions is supported by a number of findings and considerations.

Further evidence indicates that direct lymphatic drainage through the stomas of the parietal pleura is crucial in removing particles and cells, and important in removing protein from the pleural space, but should not be the main effector of fluid removal. Its importance, however, increases markedly in the presence of increased intrapleural liquid loads. Removal of protein and liquid by transcytosis, although likely on the basis of morphological findings and suggested by recent indirect experimental evidence, still needs to be directly proven to occur in the pleura. When pleural liquid volume increases, an imbalance occurs in the forces involved in turnover, which favours fluid removal. In case of a primary abnormality of one ore more of the mechanisms of pleural liquid turnover, a pleural effusion ensues. The factors responsible for pleural effusion may be subdivided into three main categories: those changing transpleural pressure balance, those impairing lymphatic drainage, and those producing increases in mesothelial and capillary endothelial permeability. Except in the first case, pleural fluid protein concentration increases above normal: this feature underlies the classification of pleural effusions into transudative and exudative.
Pathobiology of pulmonary arterial hypertension
Authors: Eddahibi S. , Morrell N. , d'Ortho M-P. , Naeije R. , Adnot S.
Published: January 2003

Recent years have witnessed important advances in the understanding of the pathophysiology of primary pulmonary hypertension (PPH). Both genetic and mechanistic studies have succeeded in identifying new molecular pathways relevant to the process of pulmonary vascular remodelling, which underlies PPH.

Mutations in the type II bone morphogenetic protein (BMP) receptor (BMPR)-II are now considered to be the genetic basis for familial PPH and ∼30% of cases of sporadic PPH. The identification of the relevance of the BMP pathway to the aetiology of PPH now raises many questions about the link between the BMPR-II mutant genotype and the PPH phenotype.

As PPH does not develop in all subjects with BMPR-II mutations, environmental or associated genetic factors may play a crucial role. Among these, the finding of an association between PPH and the L-allelic variant of the serotonin transporter (5-HTT) gene indicates that 5-HTT, which controls smooth muscle hyperplasia, probably contributes to susceptibility to PPH or is an important modifier of the PPH phenotype.

Recognition of these molecular pathways should provide insight into the pathogenesis not only of primary pulmonary hypertension, but also of secondary forms of pulmonary hypertension. This should soon lead to the development of new and more selective therapeutic approaches to pulmonary hypertension.
Sequential genotyping ofPseudomonas aeruginosafrom upper and lower airways of cystic fibrosis patients
Authors: Jung A. , Kleinau I. , Schönian G. , Bauernfeind A. , Chen C. , Griese M. , Döring G. , Göbel U. , Wahn U. , Paul K.
Published: January 2003

A controversy exists concerning the adequate specimen to characterise colonisation of cystic fibrosis (CF) airways byPseudomonas aeruginosa. Oropharyngeal, sputum and bronchoalveolar lavage samples were evaluated from 38 stable CF patients for the detection ofP. aeruginosa, genetically different isolates within the same host and longitudinal variations in the genotype during repeated examinations.

Bacterial isolates were typed by pulsed-field gel electrophoresis of deoxyribonucleic acid macrorestriction fragments.

Sensitivity, negative and positive predictive values and specificity to detectP. aeruginosawere 35.7, 73.5, 83.3 and 96.2% for oropharyngeal cultures in nonexpectorating patients and 91.7, 94.1, 100 and 100% for sputum cultures from expectorating patients, respectively. Genotypes of Pseudomonas isolates recovered from oropharyngeal swabs and sputum differed to the strains recovered by bronchoscopy in 55% and 40%, respectively. In 62% longitudinal variations in the genotype occurred. One-half of these alterations were detectable by bronchoscopy only.

In conclusion, sputum samples were of equal value as specimens from bronchoalveolar lavage to detectPseudomonas aeruginosacolonisation. Cultures from the oropharynx are not suitable for characterising bacterial conditions in the cystic fibrosis lung. Different genotypes within the same host and longitudinal genetic alterations are common and may be detectable in the bronchoalveolar lavage fluid exclusively.
Size matching in lung transplantation using predicted total lung capacity
Authors: Ouwens J.P. , van der Mark T.W. , van der Bij W. , Geertsma A. , de Boer W.J. , Koëter G.H.
Published: January 2003

Height is used in allocation of donor lungs as an indirect estimate of thoracic size. Total lung capacity (TLC), determined by both height and sex, could be a more accurate functional estimation of thoracic size. Size-matching criteria based on heightversuspredicted TLC was retrospectively evaluated, and, furthermore, whether a TLC mismatch was related to clinical and functional complications.

The ratio of donor and recipient height, as well as the ratio of predicted TLC in donors and recipients, were calculated in 80 patients after bilateral lung transplantation. Complications evaluated included persistent atelectasis, persistent pneumothorax and increased number of days in intensive care, occurrence of bronchiolitis obliterans syndrome and limitation of exercise capacity.

Median height donor/recipient ratio was 1.01 (0.93–1.12). Median predicted TLC donor/recipient ratio was 1.01 (with a clearly broader range 0.72–1.41). Neither sex mismatch nor TLC mismatch were related to clinical or functional complications.

Allocation of donor lungs based upon height alone leads to a substantial mismatch in total lung capacity caused by sex mismatch. The absence of complications suggests that a greater height donor/recipient discrepancy can be accepted for allocation than previously assumed.
Partial liquid ventilation: effects of liquid volume and ventilatory settings on perfluorocarbon evaporation
Authors: Loer S.A. , Kindgen-Milles D. , Tarnow J.
Published: January 2003

During partial liquid ventilation perfluorocarbons are eliminated mainly by evaporationviathe airways. The effects of intrapulmonary perfluorocarbon volume, respiratory rate, tidal volume, as well as the level of end-expiratory pressure on perfluorocarbon elimination from isolated lungs, were studied.

Nonperfused rabbit lungs underwent partial liquid ventilation (2–15 mL·kg−1perfluorocarbon) with variable levels of end-expiratory pressure (0–10 cmH2O), respiratory rates (15–60 breaths·min−1) and tidal volumes (3.3–10.0 mL·kg−1). Evaporative loss of perfluorocarbon was determined gravimetrically as rate of change in lung weight.

At constant respiratory settings, intrapulmonary liquid volume determined evaporative loss in a nonlinear fashion. Mean evaporation at a liquid volume of 5 mL·kg−1was 13% lower compared to evaporation at a liquid volume of 15 mL·kg−1. Any increase in end-expiratory pressure reduced perfluorocarbon evaporation,e.g.by ∼50% when end-expiratory pressure was increased from 0 to 10 cmH2O. At constant end-expiratory pressure and perfluorocarbon filling evaporation increased in a linear fashion with increasing respiratory rate and tidal volume.

In summary, the experiments suggested that evaporative loss of perfluorocarbons during partial liquid ventilation of isolated lungs is increased with increasing intrapulmonary liquid volume, respiratory rate and tidal volume and is reduced in a level-dependent fashion by the application of positive end-expiratory pressure.
Effects of terbutaline in combination with mannitol on mucociliary clearance
Authors: Daviskas E. , Anderson S.D. , Eberl S. , Chan H-K. , Young I.H. , Seale J.P.
Published: January 2003

β2-agonists and osmotic agents stimulate mucociliary clearance (MCC)viadifferent mechanisms which could potentially interact.

The effects of inhaling terbutaline in combination with mannitol on MCC were investigated in nine healthy (aged 19±1 yrs) and 11 mild (aged 21±4 yrs) asthmatic subjects. Using99mTc-sulphur colloid radioaerosol and a gamma camera, MCC was studied on four separate days with each of the following interventions: 1) terbutaline or its placebo inhaled 10 min before mannitol (in random, double blind); 2) terbutaline inhaled 5 min after mannitol; and 3) terbutaline inhaled 10 min before the control for mannitol. Lung images were collected over a period of 120 min postintervention and over 150 min in total.

The mannitol-induced increase in clearance was transiently inhibited by terbutaline pretreatment and transiently enhanced when terbutaline was administered after mannitol both in asthmatic and healthy subjects. The order of administration of mannitol and terbutaline did not affect the total clearance of radioactive mucus over 140 min from the start of intervention in both groups.

The pathways through which terbutaline and mannitol increase mucociliary clearance may transiently interact in an inhibitory or synergistic way, depending on the order of administration. However, this did not affect the overall increase in mucociliary clearance over 140 min.
Effects of salmeterol on mucosal inflammation in asthma: a placebo-controlled study
Authors: Jeffery P.K. , Venge P. , Gizycki M.J. , Egerod I. , Dahl R. , Faurschou P.
Published: January 2003

Although the anti-inflammatory effects of inhaled corticosteroids in the treatment of asthma are established, the effects of long-acting β2-adrenergic receptor agonists on inflammation are the subject of debate. The aim of the present study was to determine the effect of salmeterol on the numbers of inflammatory cells in biopsy samples of distinct immunophenotype and those expressing the genes for interleukin-4 and -5, regulatory cytokines particularly relevant to asthma.

Twenty patients (aged 18–55 yrs) with mild stable asthma were randomised in a three-way crossover study to 6 weeks of treatment with: 1) salmeterol (50 µgb.d.; SM50); 2) fluticasone propionate (250 µgb.d.; FP250), or 3) placebo.

Compared with placebo, SM50significantly reduced the numbers of neutrophils in bronchial biopsy samples and the concentrations of myeloperoxidase and soluble E-selectin in serum, each of which reflect neutrophil involvement. Compared with FP250, SM50reduced neutrophil number and human neutrophil lipocalin level in bronchial lavage fluid and intercellular adhesion molecule-1 level in bronchoalveolar lavage fluid. Compared with placebo, FP250significantly reduced the numbers of (CD3+) T-lymphocytes, (CD4+) T-helper cells, (CD45RO+) activated T-helper cells and eosinophils in the biopsy samples; it also reduced the percentage of eosinophils and soluble intercellular adhesion molecule-1 in serum. The percentage of symptom-free days and nights and airways hyperresponsiveness improved significantly after SM50compared to both placebo and FP250.

In conclusion, a novel antineutrophilic effect of the inhaled long-acting β2-adrenergic receptor agonist, salmeterol, in mild asthma is reported.
Mometasone furoate is a less specific glucocorticoid than fluticasone propionate
Authors: Austin R.J.H. , Maschera B. , Walker A. , Fairbairn L. , Meldrum E. , Farrow S.N. , Uings I.J.
Published: January 2003

Fluticasone propionate (FP) and mometasone furoate (MF) are potent synthetic corticosteroids that are widely used as anti-inflammatory agents to treat respiratory diseases. As part of the assessment of the potential for side-effects associated with their use, their activities, not only at the glucocorticoid receptor (GR) but also at the other members of the steroid nuclear receptor family, have been compared.

Cell-based functional systems were established to measure different aspects of GR function, as well as the activity at all the other steroid nuclear receptors.

The effects of MF and FP on the GR were potent and indistinguishable. Neither corticosteroid showed any activity at the oestrogen receptor, while both were weak antagonists of the androgen receptor. FP was a relatively weak agonist of the progesterone receptor but MF was a very potent agonist of the progesterone receptor, giving activity at similar concentrations to those that stimulate the GR (concentration generating 50% maximal effect (EC50)=50 pM). Moreover, while FP was a weak antagonist of the mineralocorticoid receptor (concentration generating 50% maximal inhibitory effect=80 nM), MF displayed potent partial agonist activity (EC50=3 nM, 30%).

Mometasone furoate is considerably less specific for the glucocorticoid receptor than fluticasone propionate, showing significant activity at other nuclear steroid receptors.
Effectiveness of postal smoking cessation advice: a randomized controlled trial in young men with reduced FEV1 and asbestos exposure
Authors: Humerfelt S , Eide GE , Kvale G , Aaro LE , Gulsvik A
Published: January 2003

There have been few community-based randomized, controlled intervention trials for cessation in high-risk smokers. In such a trial we evaluated the effects of postal smoking cessation advice in smokers with asbestos exposure and/or reduced forced expiratory volume in one second (FEV1). All men aged 30-45 yrs (n=22,392) living in 34 municipalities in western Norway were invited to a cross-sectional community survey. Information on smoking habits and occupational asbestos exposure were obtained from self-administered questionnaires and measurements of FEV1 were performed with dry-wedge bellow spirometers. Among 16,393 participants we identified a group of 2,610 smokers with previous occupational asbestos exposure and/or adjusted FEV1 in the lowest quartile. A random half (n=1,300) received a mailed personal letter from a respiratory physician with a person-specific health advice to quit smoking and a pamphlet on smoking cessation. The remaining smokers (n=1,310) acted as controls and did not receive any information. Twelve months after the intervention, information on smoking habits was re-examined using a postal questionnaire. Among the respondents (n=2,282), smoking cessation was reported altogether by 13.7% in the intervention group versus 9.9% in the control group (p<0.01). The 1 yr sustained quit rate (no smoking at all during the last year) was 5.6 versus 35% (p<0.05), respectively. Measurements of carbon monoxide in expired air (with < or = 10 parts per million) confirmed self-reported nonsmoking in samples of the two groups. In a community this simple postal smoking cessation advice from a respiratory physician based on person-specific risk factors improved the 1 yr sustained success rate by 60% in identified high-risk smokers.
Interleukin-8 plays a significant role in IgE-mediated lung inflammation
Authors: Erger RA , Casale TB
Published: January 2003

Interleukin (IL)-8 is a potentially important cytokine in allergic respiratory responses since it is released by many resident lung cells, and it is a potent granulocyte chemoattractant. Therefore, we induced an immunoglobulin (Ig)E-mediated response in human lung samples and studied whether IL-8 was produced in sufficient quantities to promote human neutrophil and eosinophil migration across naked filters and endothelial and pulmonary epithelial monolayers cultured on these filters. Fresh human lung fragments from 16 thoracotomy specimens were treated with either a 1:100 dilution of anti-IgE or buffer (control) for 30 min. All anti-IgE treated lung samples had significant release of histamine and neutrophil and eosinophil chemotactic activity. Fourteen of the 16 lung samples had a significant increase in IL-8 subsequent to anti-IgE treatment (p<0.01). Anti-IL-8 antibody (4 microg x mL[-1]) inhibited 42% and 53% of neutrophil and eosinophil chemotactic activity respectively, contained in supernatants from anti-IgE-treated lung samples. Finally, we found that IL-8 at a concentration near that measured after anti-IgE treatment of lung samples (2,000 pg x mL[-1]) induced neutrophil and eosinophil migration through naked filters and endothelial and pulmonary epithelial cell monolayers. Thus, human lung IgE-mediated responses in vitro results in the rapid release of interleukin-8 in amounts sufficient to affect a biological response, granulocyte transcellular migration, indicating that interleukin-8 may play a significant role in allergic respiratory diseases.
Elevated serum interferon-gamma in atopic asthma correlates with increased airways responsiveness and circadian peak expiratory flow variation
Authors: ten Hacken NH , Oosterhoff Y , Kauffman HF , Guevarra L , Satoh T , Tollerud DJ , Postma DS
Published: January 2003

Interleukin (IL)-4, IL-5 and interferon (IFN)-gamma are thought to play an important role in chronic airway inflammation in asthmatic subjects. Increased airways responsiveness and nocturnal airway obstruction are important clinical manifestations of asthma. The aim of this study was to investigate whether IL-4, IL-5 and IFN-gamma values are elevated in atopic asthma and correlate with its clinical manifestations. Serum IL-4, IL-5 and IFN-gamma levels of 17 atopic asthmatics and eight nonatopic healthy subjects were determined at 16:00 and 04:00 h by a chemiluminescence enzyme-linked immunosorbent assay (ELISA) method. The clinical manifestation of asthma was determined by assessment of the degree of airway obstruction, airways responsiveness to methacholine and severity of nocturnal airway obstruction, defined as the mean circadian (16:00-04:00 h) peak expiratory flow (PEF) variation. Serum IL-4, IL-5 and IFN-gamma levels were significantly higher in asthmatic subjects as compared to healthy controls, both at 16:00 and 04:00 h. In asthmatic subjects serum IFN-gamma at both time points correlated significantly with the provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (PC20,meth) (rho= - 0.55) and with the mean 16:00-04:00 h PEF variation (rho = 0.53). In contrast, no relationship was found between the levels of IL-4 and IL-5 and the parameters of clinical manifestation of asthma. The results suggest that the serum interferon-gamma level is a reflection of the severity of airway inflammation in atopic asthma. More studies are needed to detect the cellular sources and to clarify the exact roles of interferon-gamma and other pro-inflammatory cytokines in asthma.
CD14 expression and soluble CD14 after segmental allergen provocation in atopic asthma
Authors: Virchow JC  , Julius P , Matthys H , Kroegel C , Luttmann W
Published: January 2003

Allergic asthma is associated with the recruitment of activated inflammatory cells after allergen challenge. Surface expression of CD14 has been proposed as a marker of cell activation and differentiation. We therefore measured CD14 expression on activated macrophages and granulocytes as well as soluble CD14 (sCD14) concentrations in peripheral blood and bronchoalveolar lavage (BAL) following segmental allergen provocation (SAP) with individually standardized doses of allergen in eight patients with allergic asthma. Two segments of the right lung were challenged with allergen. Two segments of the left lung, into which saline was instilled, served as controls. CD14 expression on macrophages and granulocytes was determined by flow-cytometry and concentrations of interleukins and sCD14 were analysed by enzyme-linked immunosorbent assay (ELISA) 10 min and 18 h after challenge. Soluble CD14 concentrations remained unchanged in BAL fluid after saline challenge and 10 min after SAP, but increased significantly 18 h after SAP. Although macrophage numbers increased 18h after SAP, CD14 expression on these cells did not change. Unlike macrophages, granulocyte numbers correlated with sCD14 levels 18 h after SAP while their CD14 expression decreased significantly. Furthermore, sCD14 correlated with interleukin (IL)-13 concentrations 18 h after SAP. An increase in soluble CD14 can be observed 18 h but not 10 min after segmental allergen provocation suggesting local release of this surface antigen. Our findings imply that CD14-mediated cell activation following segmental allergen provocation could play a role in asthmatic inflammation.
Bronchial temperature reflects transcapillary heat transport of isolated blood-perfused rabbit lungs
Authors: Loer SA , Arndt JO
Published: January 2003

The pulmonary capillaries are in such close proximity to the terminal airways that changes in capillary blood temperature should also cause changes in bronchial wall temperature. Therefore, we hypothesized that injection of cold solutions into the pulmonary artery would yield bronchial temperature-time curves similar to those in the pulmonary artery and left atrium. These bronchial curves should mainly represent the capillary bed. Isolated rabbit lungs (n=8) were ventilated (5% CO2 in air) and perfused (autologous blood, 37 degrees C) at various flow rates (50-200 mL x min[-1]). Thermistor probes (diameter 0.46 mm) registered temperature changes in the pulmonary artery, at the bronchial wall (wedge position) and in the left atrium after injection of 0.8 mL Ringer's lactate (0 degrees C) into the pulmonary artery. Bronchial temperature-time curves were found to resemble "dilution" curves located between pulmonary arterial and left atrial curves. Independent of flow rate, their appearance times, peaks and calculated mean transit times were between those from the pulmonary artery and the left atrium. We conclude that bronchial temperature-time curves reflect transcapillary heat transport and that this approach might be useful in gaining further information about vascular transport processes in the interior of the lung.
Clinical effect of Diskus dry-powder inhaler at low and high inspiratory flow-rates in asthmatic children
Authors: Nielsen KG , Auk IL , Bojsen K , Ifversen M , Klug B , Bisgaard H
Published: January 2003

In vitro studies with the Diskus inhaler at low and high flow rates show consistent doses of drug as fine particles <4.7 microm. The present study was designed to ascertain whether this in vitro flow independency translates into flow-independent clinical effect when the device is used by patients at low (30 L x min[-1]) and high (90 L x min[-1]) flow rates. A pilot study in 129 children aged 3-10 yrs demonstrated that 99% of children of 3 yrs and above can generate a flow > or = 30 L x min(-1) through the device, while 26% performed > or = 90 L x min(-1). Eighteen children aged 8-15 yrs with exercise induced asthma inhaled placebo or salmeterol 50 microg at either 30 L x min(-1) or 90 L x min(-1). Exercise challenges were carried out 1 h and 12 h after dosing. The maximum percentage fall in forced expiratory volume in one second (FEVI) after exercise 12 h after treatment was significantly less after salmeterol at either flow rates as compared to placebo. There was no significant difference in the protection from salmeterol on the day of low-flow inhalation versus the day of high-flow inhalation. Consistent in vitro fine particle dosing from the Diskus inhaler translates into a consistent clinical effect at low and high flow rates in children.
Effect of dietary intake of omega-3 and omega-6 fatty acids on severity of asthma in children
Authors: Hodge L , Salome CM , Hughes JM , Liu-Brennan D , Rimmer J , Allman M , Pang D , Armour C , Woolcock AJ
Published: January 2003

We assessed the clinical and biochemical effects in asthmatic children of fish oil supplementation and a diet that increases omega-3 and reduces omega-6 fatty acids. Thirty nine asthmatic children aged 8-12 yrs participated in a double-blind, randomized, controlled trial for 6 months during which they received fish oil capsules plus canola oil and margarine (omega-3 group) or safflower oil capsules plus sunflower oil and margarine (omega-6 group). Plasma fatty acids, stimulated tumour necrosis factor alpha (TNFalpha) production, circulating eosinophil numbers and lung function were measured at baseline and after 3 and 6 months of dietary modification. Day and night symptoms, peak flow rates and medication use were recorded for 1 week prior to laboratory visits. Plasma phospholipid omega-3 fatty acids were significantly greater in the omega-3 group at 3 and 6 months compared to the omega-6 group (p<0.001). In the omega-3 group TNFalpha production fell significantly compared with baseline (p=0.026), but the magnitude of change between groups did not reach significance (p=0.075). There were no significant changes in clinical outcome measures. Dietary enrichment of omega-3 fatty acids over 6 months increased plasma levels of these fatty acids, reduced stimulated tumour necrosis factor alpha production, but had no effect on the clinical severity of asthma in these children.
Inhaled nitric oxide in hypoxaemic newborns who are candidates for extracorporeal life support
Authors: Biban P , Trevisanuto D , Pettenazzo A , Ferrarese P , Baraldi E , Zacchello F
Published: January 2003

The aim of this study was to evaluate the effect of inhaled nitric oxide (NO) in newborns with acute hypoxaemic respiratory failure and the impact of this NO therapy on survival and the need for extracorporeal membrane oxygenation (ECMO). A cohort of newborns with a gestational age of > or = 34 weeks and an oxygenation index (OI) > 25 were prospectively evaluated. Patients were given NO at an initial dose of 10 parts per million (ppm). Oxygenation parameters were evaluated prior and during NO inhalation. From January 1994 to December 1996, 20 infants were enrolled in the study. Based upon their outcome, patients were divided into two groups: survivors with no need for ECMO, group A (n=8) and survivors requiring ECMO or nonsurvivors, group B (n=12). All infants approached or met ECMO criteria before NO inhalation. Eight patients (40%) were successfully managed with NO and conventional treatment (group A). Newborns in this group showed a rapid and sustained improvement of systemic oxygenation during NO inhalation. Mean arterial oxygen tension (Pa,O2) increased significantly from 4.5 kPa (34 mmHg) (95% confidence interval (95% CI) 1.9-7.1 kPa (14.4-53.7 mmHg)) to 10.1 kPa (75.7 mmHg) (95% CI 6.5-13.6 kPa (49.1-1023 mmHg)) after 1 h and was 9.0 kPa (67.7 mmHg) (95% CI 7.1-11.0 kPa (53.1-82.4 mmHg)) at 24 h. Conversely, none of the oxygenation parameters improved in the 12 patients who ultimately required ECMO or died (group B). The results indicate that inhaled nitric oxide can improve systemic oxygenation in newborns with acute respiratory failure and may reduce the need for extracorporeal membrane oxygenation support in candidates. Lack of a rapid response to nitric oxide may be an early predictor of unfavourable short-term outcome, prompting a move towards alternative treatments.
Hydrogen peroxide-induced epithelial injury: the protective role of intracellular nonprotein thiols (NPSH)
Authors: Mulier B , Rahman I , Watchorn T , Donaldson K , MacNee W , Jeffery PK
Published: January 2003

Injury to the alveolar region is a hallmark of the adult respiratory distress syndrome (ARDS) whereas injury to the epithelium of the conducting airways is a characteristic of asthma. Reactive oxygen species have been implicated as mediators of lung injury in both of these conditions. We have investigated the relationship between intracellular nonprotein thiols (NPSH), and the release of the cytosolic enzyme lactate dehydrogenase (LDH), as an index of cell injury, following treatment of the human alveolar type II-like epithelial cell line (A549 cells) or the human bronchial epithelial cell line (16HBE140-) with hydrogen peroxide (H2O2). We have also assessed the protective effects of pre-incubation of both of these cells lines with H2O2 or enhancement of intracellular NPSH against H2O2-induced cell injury. Exposure of A549 and 16HBE140- cells to H2O2 (0.1 mM and 1 mM respectively for 16 h) produced the release of 40% of the total cellular LDH. H2O2 exposure produced an initial dose-dependent decrease in NPSH in A549 cells, with a subsequent increase to above control values. 16HBE140- cells also showed a dose-dependent decrease in NPSH following exposure to H2O2. Pretreatment of A549 cells with 0.1 mM H2O2 followed by subsequent exposure to H2O2 did not protect against H2O2-induced LDH release in this epithelial cell line. Pre-incubation with 2 mM N-acetylcysteine (NAC) increased NPSH but not intracellular reduced glutathione and resulted in total inhibition of H2O2-induced LDH release in both cell types. Pretreatment with reduced glutathione protected both cell types against the injurious effects of H2O2, whereas glutathione monethyl ester (GSHMEE) only partially protected A549 cells and had no effect in 16HBE140- cells. Intracellular cysteine levels were increased in both cell lines following NAC exposure but not sufficiently to account for the increase in NPSH levels. These observations raise the possibility that a critical concentration of nonprotein thiols may be necessary to protect pulmonary epithelial cells against hydrogen peroxide-induced injury.
Hypoxia reduces endothelin production by rat alveolar type II cells in primary culture
Authors: Crestani B , Odoux C , Rolland C , Moldovan F , Cornillet P , Fiet J , Aubier M
Published: January 2003

The purpose of the study was to describe endothelin (ET) production and to characterize the effect of hypoxia on preproendothelin-1 (preproET-1) messenger ribonucleic acid (mRNA) expression and ET secretion by rat type II pneumocytes in vitro. Rat type II pneumocytes were incubated in a sealed chamber containing a normoxic (21% O2) or hypoxic (1% O2) atmosphere for increasing durations. Immunoreactive ET (irET) was measured in cell supernatants using a radioimmunoassay. Rat preproET-1 mRNA was detected by Northern blot. Rat type II pneumocytes expressed preproET-1 mRNA, contained irET and secreted irET in a time-dependent manner. ET secretion was dependent on de novo ribonucleic acid (RNA) and protein synthesis. Hypoxia decreased irET secretion by 27% and reduced the steady-state level of preproET-1 mRNA by 60% whereas intracellular irET concentration was unchanged. Inhibition was partially reversible with the return to a normoxic atmosphere. Inhibition of nitric oxide synthesis did not prevent the inhibitory effect of hypoxia. In conclusion, rat type II pneumocytes in primary culture secreted immunoreactive endothelin and expressed preproendothelin-1 messenger ribonucleic acid. Hypoxia reversibly reduced endothelin-1 production through a reduction of the steady-state preproendothelin-1 messenger ribonucleic acid level. Nitric oxide synthesis did not mediate the inhibitory effect of hypoxia.
Effects of proportional assist ventilation on exercise tolerance in COPD patients with chronic hypercapnia
Authors: Bianchi L , Foglio K , Pagani M , Vitacca M , Rossi A , Ambrosino N
Published: January 2003

This study investigates the impact of proportional assist ventilation (PAV), a new mode of partial ventilatory support, on exercise tolerance and breathlessness in severe hypercapnic chronic obstructive pulmonary disease (COPD) patients. We also examined the effects of continuous positive airway pressure (CPAP) and pressure support ventilation (PSV). On two consecutive days, 15 stable hypercapnic COPD patients underwent four endurance tests on a cycle ergometer at 80% of their maximal workrate, receiving, via a nasal mask in random order, either: 1) sham ventilation (CPAP: 1 cmH2O); 2) CPAP (6 cmH2O); 3) PSV (inspiratory pressure support: 12-16 cmH2O; expiratory positive airway pressure (EPAP): 1 cmH2O); or 4) PAV (8.6+/-3.6 cmH2O x L(-1) and 3+/-1.3 cmH2O x L(-1)x s(-1) of volume and flow assistance, respectively plus EPAP: 1 cmH2O). Oxygen supply was standardized to maintain an arterial oxygen saturation (Sa,O2) of 92-93%. Breathing pattern and minute ventilation (by respiratory inductive plethysmography), pulse oximetry, end tidal partial pressure of CO2, cardiac frequency and sensations of dyspnoea and leg discomfort (by Borg scale) were monitored. In comparison to sham ventilation, PAV, PSV and CPAP were able to increase the endurance time (from 7.2+/-4.4 to 12+/-5.6, 10+/-5.2 and 9.6+/-4.6 min, respectively) and to reduce dyspnoea and oxygen flow to the nasal mask. However, the greatest improvement was observed with PAV. We conclude that PAV delivered by nasal mask can im-prove exercise tolerance and dyspnoea in stable hypercapnic COPD patients and hence this mode of ventilatory support may be useful in respiratory rehabilitation programmes.
Time course of pulmonary artery pressure during sleep in sleep apnoea syndrome: role of recurrent apnoeas
Authors: Sforza E , Laks L , Grunstein RR , Krieger J , Sullivan CE
Published: January 2003

Recent results in animals have suggested that repetition of hypoxaemic stimuli may result in a progressive increase in pulmonary arterial pressure (Ppa). The purpose of the present study was to investigate the effects of recurrent obstructive apnoeas on Ppa. We have, therefore, examined the nocturnal trend of Ppa in seven obstructive sleep apnoea syndrome (OSAS) patients and in five snorers. Mean Ppa was measured before, at the start, at the end and after the selected apnoeas. The analysis was performed for each 1 h period for at least 7 h throughout the night on at least 10 randomly selected apnoeas per hour. In snorers, 100 randomly chosen values were measured during every hour of the night. In the morning after the nocturnal study, the Ppa responses to acute hypoxia and hypercapnia were measured. No Ppa changes throughout the 7 h were found during sleep in snorers [Ppa slope:-0.002+/-0.10 mmHg x h(-1)]. In OSAS patients a small but significant increase in Ppa throughout the night was noted, affecting the values before [Ppa slope: 0.7+/-0.16 mmHg x h(-1)], at the start of apnoea [Ppa slope: 0.530.1 mmHg x h(-1)] as well as at the end [Ppa slope: 0.44+/-0.08 mmHg x h(-1)] and in the postapnoeic period [Ppa slope: 0.55+/-0.1 mmHg x h(-1)]. When we limited the analysis to nonrapid eye movement (NREM) sleep, a trend in progressive Ppa was also present, irrespective of changes in apnoea duration and apnoea desaturation. The Ppa rise during the night was not affected by diurnal Ppa pulmonary vascular response to hypoxia and hypercapnia or indices of sleep apnoea severity. We conclude that in obstructive sleep apnoea, pulmonary artery pressure progressively increases during the night, reflecting the cumulative effects of apnoeas and nocturnal hypoxaemia.
Mandibular advancement devices for the control of snoring
Authors: Stradling  , Negus TW , Smith D , Langford B
Published: January 2003

Patients presenting with the complaint of antisocial snoring have very few options available to them of proven efficiency. Mandibular advancement devices worn intra-orally at night, have recently been shown in controlled trials to help mild to moderate obstructive sleep apnoea. However, there are no properly controlled studies with objective measurements on the use of such appliances for the management of antisocial snoring. Fifteen patients, already established on mandibular advancement devices for the control of snoring, were asked to participate in this study. They were studied over two nights, using a portable sleep monitoring device at home, both with and without their mandibular advancement devices in place (in randomized order). Snoring was measured using a surface throat microphone. In addition oxygen saturation and indirect beat to beat blood pressure were measured. The latter (using pulse transit time) provided an index of autonomic "arousals" and a measure of inspiratory effort. In nearly all of these highly selected patients the mandibular advancement devices reduced significantly the amount of snoring from a median of 193 to 20 snores x h(-1) (p<0.0001). In addition there was a reduction in respiratory effort, implying enlargement of the upper airway whilst wearing the appliance. These patients only represent those who were able to tolerate the appliance. With such clear evidence of their potential efficacy, and no suggestion from other studies of any harm, it would seem reasonable to introduce this approach into the management of antisocial snoring.
Respiratory muscles as a target for adenovirus-mediated gene therapy
Authors: Petrof BJ
Published: January 2003

The protein dystrophin is absent in the muscles of patients with Duchenne muscular dystrophy (DMD) as well as dystrophin-deficient mice with muscular dystrophy (mdx mice). The mdx mouse diaphragm closely resembles the human DMD phenotype and thus provides a useful model for studies of dystrophin gene replacement. Recombinant adenovirus vectors (AdVs) hold promise as a means for delivering a functional dystrophin gene to muscle. As an initial step toward this goal, we have determined the efficiency and functional consequences of AdV-mediated reporter gene transfer to the diaphragm in both normal and mdx adult mice. At 1 week after AdV administration, there was a high level of transgene expression in the diaphragm. One month later, however, elimination of transgene expression was observed along with a significant decrease in force production by both normal and mdx diaphragms. Immunosuppression with cyclosporine did not augment the level of transgene expression, but a beneficial effect on diaphragm force-generating capacity was observed in both groups of animals. In order to further elucidate the cellular mechanisms underlying these findings, the effects of AdV gene inactivation (by ultraviolet (UV) irradiation) and interference with host T-lymphocyte subsets were examined. Both UV-inactivation of AdV and CD8+ T-cell deficiency were found to significantly alleviate AdV-induced reductions in diaphragm force-generating capacity. Brief (2 day) administration of a neutralizing antibody against host CD4+ T-cells also produced a trend towards mitigation of AdV-induced contractile dysfunction. In addition, transgene expression one month after AdV delivery was significantly enhanced with inhibition of either CD4+ or CD8+ T-cell function. The data suggest two major sources of reduced force generation after recombinant adenovirus vector-mediated gene transfer to muscle: 1) a cytotoxic component associated with recombinant adenovirus vector transcriptional activity; and 2) an immune-based component of more delayed onset that is primarily dependent upon CD8+ T-cell activity. These results have important implications for the design of future generation vectors and the potential need for immunosuppressive therapy after recombinant adenovirus vector mediated dystrophin gene transfer to Duchenne muscular dystrophy patients.
Functional upper airway obstruction and chronic irritation of the larynx
Authors: Rothe TB , Karrer W
Published: January 2003

Wheezing and dyspnoea are typical symptoms of asthma but can also be found in diseases of the extrathoracic airways. Functional upper airway obstruction may imitate, as well as complicate asthma. Functional upper airway obstruction was first described as a conversion disorder in young females with inspiratory stridor. Subsequently, it was found that functional upper airway obstruction was more often a secondary phenomenon in chronic asthma also involving the expiratory laryngeal airflow. During a period of 15 months, we diagnosed six cases of functional upper airway obstruction. Five patients were female and one male, and four were also asthmatics. Three cases showed chronic sinusitis with postnasal drip (PND) and/or gastro-oesophageal reflux. Both disorders may irritate the larynx. Treatment of sinusitis and gastro-oesophageal reflux led to a significant improvement of dyspnoea in all three of these patients. In asthma refractory to treatment and in the case of an asthmatic exacerbation without obvious cause, functional upper airway obstruction should be excluded to avoid unnecessary treatment with systemic steroids. Some of the possible causative factors of functional upper airway obstruction, such as postnasal drip and gastro-oesophageal reflux, are easily treatable.
Diffuse alveolar damage in a patient treated with gemcitabine
Authors: Marruchella A , Fiorenzano G , Merizzi A , Rossi G , Chiodera PL
Published: January 2003

We present a case of diffuse alveolar damage (DAD) that occurred in a male aged 68 yrs treated with gemcitabine, a novel antineoplastic agent, that was given for hepatic relapse of a previously resected non-small cell lung cancer. The patient developed acute respiratory failure after the sixth drug dose, and died 4 days after admission. Autopsy revealed a pattern of DAD. No evidence of infection or other specific aetiologies could be found. To our knowledge, only three cases of pulmonary toxicity resulting from treatment with gemcitabine have been published; two of them were fatal and postmortem examination revealed a pattern consistent with acute respiratory distress syndrome. A careful survey may determine the incidence of pulmonary toxicity of this new drug in the future.
Extreme and near-extreme climate change data in relation to building and plant design
Authors: Chow D HC , Levermore G , Jones P , Lister D , Laycock P J , Page J
Published: January 2003

Buildings and plant are designed utilizing near-extreme weather data. The present data used are brie‘ y discussed, including manual near-extreme percentiles for manual design and hourly data for simulation on a PC (test reference years and design summer years, and near-extreme periods). However, with climate change occurring, designs based on current data will produce uncomfortable summer thermal conditions within and around buildings in the future. This expected change is especially relevant now, as buildings have to last typically from 50 to 100 years. Climate change data for the future are needed to assess the performance of buildings and plant in the future. The Hadley Centre climate change models could provide such data. In this paper analysis of extreme data from one model, the HadCM3 model (south-east England grid box) with an appropriate climate change scenario, are considered in relation to their use for design assessment. Dry bulb temperature and solar irradiance extreme values are considered in this paper. The expected trend in both minimum and maximum temperature is for both to increase with time, but the maxima are found to rise faster than the minima. There are two factors in‘ uencing the solar radiation estimates, the basic clarity of the atmosphere and the seasonal amount of cloud. The latter is predicted to increase slightly in winter and decrease slightly in summer. The variations in the predicted short-wave radiation values re‘ ect the expected combined impacts of these two factors. The implications of these results are brie‘ y discussed.
Cladding strategies for building-integrated photovoltaics
Authors: Jones A D , Underwood C P
Published: January 2003

Photovoltaic cladding on the surfaces of commercial buildings has the potential for considerable reductions in carbon emissions due to embedded renewable power generation displacing conventional power utilization. In this paper, a model is described for the optimization of photovoltaic cladding densities on commercial building surfaces. The model uses a modi” ed form of the ‘fill factor’ method for photovoltaic power supply coupled to new regression-based procedures for power demand estimation. An optimization is included based on a de” ned ‘mean index of satisfaction’ for matched power supply and demand (i.e., zero power exportation to the grid). The mean index of satisfaction directly translates to the reduction in carbon emission that might be expected over conventional power use. On clear days throughout the year, reductions of conventional power use of at least 60% can be achieved with an optimum cladding pattern targeted to lighting and small power load demands.