bluuebunny/crossref_metadata_2025 huggingface dataset:
Neutrophils and the calcium‐binding protein MRP‐14 mediate carrageenan‐induced antinociception in mice
Authors: Pagano Rosana L. , Dias Maria Angela Amorim , Dale Camila S. , Giorgi Renata
Published: November 2002

Background: We have previously shown that the calcium‐binding protein MRP‐14 secreted by neutrophils mediates the antinociceptive response in an acute inflammatory model induced by the intraperitoneal injection of glycogen in mice.

Aim: In an attempt to broaden the concept that neutrophils and MRP‐14 controls inflammatory pain induced by different type of irritants, in the present study, after demonstrating that carrageenan (Cg) also induces atinociception in mice, we investigated the participation of both neutrophils and MRP‐14 in the phenomenon.

Methods: Male Swiss mice were injected intraperitoneally with Cg and after different time intervals, the pattern of cell migration of the peritoneal exudate and the nociceptive response of animals submitted to the writhing test were evaluated. The participation of neutrophils and of the MRP‐14 on the Cg effect was evaluated by systemic inoculation of monoclonal antibodies anti‐granulocyte and anti‐MRP‐14.

Results: Our results demonstrate that the acute neutrophilic peritonitis evoked by Cg induced antinociception 2, 4 and 8 h after inoculation of the irritant. Monoclonal antibodies anti‐granulocyte or anti‐MRP‐14 reverts the antinociceptive response only 2 and 8 h after Cg injection. The antibody anti‐MRP‐14 partially reverts the antinociception observed after 4 h of Cg injection while the anti‐granulocyte antibody enhances this effect. This effect is reverted by simultaneous treatment of the animals with both antibodies. After 4 h of Cg injection in neutrophil‐depleted mice a significant expression of the calcium‐binding protein MRP‐14 was detected in the cytoplasm of peritoneal macrophages. This suggests that the enhancement of the effect observed after treatment with the anti‐neutrophil antibody may be due to secretion of MRP‐14 by macrophages. It has also been demonstrated that endogenous opioids and glucocorticoids are not involved in the antinociception observed at the 4th hour after Cg injection.

Conclusion: These data support the hypothesis that neutrophils and the calcium‐binding protein MRP‐14 are participants of the endogenous control of inflammatory pain in mice despite the model of acute inflammation used.
Real-space renormalisation-group theory for Anderson localisation: decimation method for electron systems
Authors: H Aoki
Published: November 2002

A new real-space renormalisation-group method is developed for electron systems. The equation for the Green function is reduced to that for the Green function in a decimated space to obtain the renormalised Hamiltonian. This formalism is applied to the two-dimensional disordered electron systems in the Anderson model. It is shown that the whole probability distribution Pv(Vij(n); mod ri-rjmod ), of the renormalised transfer energies, Vij(n), can be characterised by gaussian distributions in the logarithmic scale. In particular the average of Vij(n)behaves as (Vjj(n))2)1/2varies as exp(- gamma(n)(E) mod ri-rjmod ), where the decay coefficient gamma(n)(E) tends to zero as the author approaches the extended regime. The transformation property of the system against decimation is discussed in terms of the flow diagram of the probability distribution functions for the renormalised Hamiltonian.
Computer studies of local minima of the planar spin glass
Authors: R B Grzonka  , M A Moore
Published: November 2002

The nature of the local minima of the 'planar' spin glass Hamiltonian at zero temperature in two and three dimensions is investigated by means of computer simulation. The authors find that the eigenvalue density rho ( lambda ) of the Hessian varies as lambda1/2for small lambda in three dimensions but that only approximately 40% of this can be accounted for by a spin-wave argument. In two dimensions all the eigenvectors appear to be localised but in three dimensions there appears to be a sharp transition from extended to localised states at a critical value of lambda . The addition of a uniform magnetic field or uniaxial or cubic anisotropy also produces in three dimensions localised states at small values of lambda , together with a large reduction in rho ( lambda ) as lambda to 0. The authors deduce that the 'hole' picture of the dynamics (based on the assumption that the system stays in the vicinity of a particular local minimum for macroscopic periods) is not likely to be an accurate description at long times.
Characteristics of Thermogravimetric Plants
Authors: Arosio S. , Carlevaro R.
Published: November 2002

A nonconventional thermodynamic converter, called thermogravimetric system, capable of generating mechanical-electric energy is described in the present work. Such plant is basically an interesting application of a liquid-vapor two-phase flow, evolving in elevated vertical ducts of a large diameter. The most significant plants—those working with liquid lead/steam and liquid lead/PP 50 C5F12—have been analyzed in more detail. Plant height Z, power W (0.5–4 MW), and overall efficiency ηo have been evaluated through an appropriate calculus code, particularly regarding the two-phase flow behavior.
Measuring Reservoir Compaction Through Radioactive Marker Technique
Authors: Macini Paolo , Mesini Ezio
Published: November 2002

Radioactive Marker Technique (RMT), an in-situ method to measure reservoir rock compaction and to evaluate uniaxial compressibility coefficients Cm, is examined here. Recent field applications seems to confirm that RMT-derived Cm’s match with sufficient precision with those calculated from land subsidence observed over the field by means of geodetic surveys, but are not always in good agreement with those derived from lab measurements. In particular, here is reported an application of RMT in the Italian Adriatic offshore, which highlights the discrepancies of Cm’s measurements from lab and RMT. At present, these discrepancies aren’t thoroughly understood, so, from an applicative standpoint, it is still necessary to perform a critical comparison and integration between both set of data.
A LCA/LCC Optimized Selection of Power Plant System With Additional Facilities Options
Authors: Widiyanto Anugerah , Kato Seizo , Maruyama Naoki
Published: November 2002

In the past, the selection of an energy resource for electricity generation was dominated by finding the least expensive power generating plant. Although such an approach is essential, there is growing concern about other aspects of power generation such as social, environmental and technological benefits and consequences of the energy source selection. The aims of this paper are first to introduce a life cycle assessment (LCA) scheme with the aid of the NETS (Numerical Eco-load Total Standardization) method that we have newly proposed. This method provides a numerical measure for evaluating the quantitative load of any industrial activity on the environment, and has been used to analyze the energy flow and the environmental loads of various power generation systems. A second goal is to develop a computer program to examine the applicability of technology options based on cost performance and environmental load reduction. A final goal of this work is to select the power system using life cycle assessment (LCA) and life cycle costing (LCC). As a result, environmental load and economical cost for various power generation systems are discussed from the LCA point of view for further ecological improvement.
Analysis of a Large Scale Liquid Hydrogen Dispersion Using the Multi-Phase Hydrodynamics Analysis Code (CHAMPAGNE)
Authors: Chitose K. , Okamoto M. , Takeno K. , Hayashi K. , Hishida M.
Published: November 2002

It is planned to use hydrogen extensively as a source of clean energy in the new century. As part of our investigation for an International Clean Energy Network Using Hydrogen Conversion (WE-NET), we have been studying to establish a safety scheme to ensure that both existing and new hydrogen technologies are implemented without endangering public safety. In this plan, we consider the transport and storage of a large quantity of hydrogen in a large tank. First we must evaluate the consequence of the postulated accident of liquid hydrogen. Since we have developed the multi-phase hydrodynamics analysis code (CHAMPAGNE), we apply the code to simulate the formation and dispersion of hydrogen vapor clouds. In the present paper we have improved the calculation model in two ways. We added a function to CHAMPAGNE for solving evaporation phenomena realistically, made many parametric calculations and planned the small-scale hydrogen dispersion experiments for the validation of this model. Another improvement is the turbulent mixing of evaporated liquid hydrogen. Now we have completed the basic functions of our simulation code. And these models of CHAMPANGE code must be verified by the experimental data.
Inflow Performance and Pressure Interference in Dual-Completed Wells With Water Coning Control
Authors: Wojtanowicz Andrew K. , Shirman Ephim I.
Published: November 2002

Dual-completed wells with Downhole Water Sink (DWS) are used for water coning control in oil reservoirs with bottom water drive. In DWS wells, the second (bottom) completion—placed in the water column—is used for draining water. This prevents the water cone invasion and allows free oil inflow in the top completion. The decision on using DWS or a conventional (single-completed) well is based upon deliverability comparison of the two wells. This paper shows how to describe DWS well deliverability in terms of the top and bottom production rates, water cut, and pressure drawdown. Also, the effect of pressure interference between two well completions on deliverability limits has been studied and qualified experimentally. DWS well deliverability depends on two variables, pressure drawdown and water drainage rate, and is described by a three-dimensional Inflow Performance Domain (IPD). Visual-Basic software based on a new analytical model of IPD has been developed to calculate critical (fluid breakthrough) rates for oil and water. The critical rates identify inflow conditions to the well’s completions—single or two-phase inflow. Also calculated are the values of water cut and maximum pressure drawdown at the well. An example demonstrates the procedure and a complete IPD plot. The experimental study, using a Hele-Shaw physical model of DWS well, demonstrates the reduction of well’s deliverability caused by pressure interference from the second (bottom) completion. The experiments have shown, however, that the deliverability decrease is small and over-compensated by the increase of oil rate due to simultaneous reduction of water cut.
College physics students’ epistemological self-reflection and its relationship to conceptual learning
Authors: May David B. , Etkina Eugenia
Published: November 2002

Students should develop self-reflection skills and appropriate views about knowledge and learning, both for their own sake and because these skills and views may be related to improvements in conceptual understanding. We explored the latter issue in the context of an introductory physics course for first-year engineering honors students. As part of the course, students submitted weekly reports, in which they reflected on how they learned specific physics content. The reports by 12 students were analyzed for the quality of reflection and some of the epistemological beliefs they exhibited. Students’ conceptual learning gains were measured with standard survey instruments. We found that students with high conceptual gains tend to show reflection on learning that is more articulate and epistemologically sophisticated than students with lower conceptual gains. Some implications for instruction are suggested.
Relativistic causality and conservation of energy in classical electromagnetic theory
Authors: Kislev A. , Vaidman L.
Published: November 2002

Causality puts certain constraints on the change of the electromagnetic field due to the change in motion of charged particles. Naive calculations of the electromagnetic energy and the work performed by the electromagnetic fields which take these constraints into account might lead to paradoxes involving the apparent nonconservation of energy. A few paradoxes of this type for the simple motion of two charges are presented and resolved in a quantitative way providing deeper insight into various relativistic effects in classical electromagnetic theory.
Effects of exposure conditions on the depletion of antioxidants from high-density polyethylene (HDPE) geomembranes
Authors: Sangam Henri P , Rowe R Kerry
Published: November 2002

Laboratory-accelerated ageing tests have been conducted to examine the depletion of antioxidants from high-density polyethylene (HDPE) geomembranes as a result of their exposure to various environments. Samples of 2.0 mm thick geomembrane were exposed to air, water, and municipal solid waste (MSW) leachate at temperatures of 22, 40, 55, 70, and 85°C. At various time intervals, samples were collected and the oxidative induction time (OIT) was evaluated. The results indicated that the antioxidants are depleted at rates 1.6 to 2.4 times faster for samples in water than for air-exposed samples. For samples in leachate, the depletion is about 4 times faster than that in air and 1.63.2 times faster than that in water. Using these rates, it is estimated that if the geomembrane examined were used as an MSW landfill primary liner, it would take at least 40 years to deplete the antioxidants from the geomembrane at a temperature of 33°C and over 150 years at a temperature of 13°C.Key words: ageing, antioxidants, durability, oxidative induction time, HDPE geomembrane, antioxidant depletion time.
Aspects of the behaviour of compacted clayey soils on drying and wetting paths
Authors: Fleureau Jean-Marie , Verbrugge Jean-Claude , Huergo Pedro J , Correia António Gomes , Kheirbek-Saoud Siba
Published: November 2002

A relatively large number of drying and wetting tests have been performed on clayey soils compacted at the standard or modified Proctor optimum water content and maximum density and compared with tests on normally consolidated or overconsolidated soils. The results show that drying and wetting paths on compacted soils are fairly linear and reversible in the void ratio or water content versus negative pore-water pressure planes. On the wet side of the optimum, the wetting paths are independent of the compaction water content and can be approached by compaction tests with measurement of the negative pore-water pressure. Correlations have been established between the liquid limit of the soils and such properties as the optimum water content and negative pore-water pressure, the maximum dry density, and the swelling or drying index. Although based on a limited number of tests, these correlations provide a fairly good basis to model the dryingwetting paths when all the necessary data are not available.Key words: compaction, unsaturated soils, clays, drying, wetting, Proctor conditions.
CONSTRUCTING RED-BLACK TREE SHAPES
Authors: MANTLER ANDREA , CAMERON HELEN
Published: November 2002

Cormen et al. describe efficient algorithms for inserting nodes into and deleting nodes from red-black trees. If some binary trees satisfying the definition of red-black trees cannot be built by these algorithms, then theoretical analyses of red-black trees that consider all binary trees satisfying the definition of red-black trees may not accurately describe the behavior of red-black trees in practice. We show that any binary tree shape that satisfies the definition of red-black trees can be built using only the insertion algorithm, RB-INSERT, of Cormen et al. We first describe an algorithm, RB-SHAPE, which, given any red-black tree T, will construct an insertion sequence for T. When the constructed sequence of insertions is performed on the empty tree using RB-INSERT, the result is a red-black tree with the same shape as T. We then prove the correctness of algorithm RB-SHAPE.
Calculating the Expected Loss of Diversity of Selection Schemes
Authors: Motoki Tatsuya
Published: November 2002

This paper concerns a measure of selective pressure, called filoss of diversity, fl that denotes the proportion of unselected individuals during the selection phase. We probabilistically calculate the expected value and variance of loss of diversity in tournament selection, truncation selection, linear ranking selection, and exponential ranking selection. From numerical results, we observe that in tournament selection, many more individuals are expected to be lost than with Blickle and Thiele's static estimate. We also observe that tournament and exponential ranking schemes potentially bring about nearly equivalent selection behaviors but have different types of control parameters.
Pulmonary fibrosis: cytokines in the balance
Authors: Coker RK , Laurent GJ
Published: November 2002

Pulmonary fibrosis can complicate diverse pulmonary and systemic pathologies. In many cases the underlying cause remains unidentified. Mortality from the disease is increasing steadily in the UK and USA. The clinical features are well-described, but patients frequently present at an advanced stage, and current treatments have not improved the poor prognosis. There is a compelling need to identify the fibrotic process earlier and to develop new therapeutic agents. Increased collagen deposition is central to the pathology and interest over the last decade has focused on the role of cytokines in this process. These polypeptide mediators are believed to be released from both circulating inflammatory and resident lung cells in response to endothelial and epithelial injury. Key cytokines currently implicated in the fibrotic process are transforming growth factor-beta, tumour necrosis factor-alpha and endothelin-1. This article outlines the evidence implicating these mediators in the pathogenesis of pulmonary fibrosis and also considers the possible role of cytokines with antifibrotic effects, such as interferon-gamma. The "balance" of positively and negatively regulating cytokines is discussed, and the potential for interaction with other factors including viruses, hormones and altered antioxidant status is also considered. Finally, potential novel therapeutic approaches are discussed, together with suggestions for future studies and clinical trials. As the outcomes of different avenues of research over the last ten years are brought together, it is clear that there is now a hitherto unrivalled opportunity to begin to tackle the treatment of this devastating disease.
Montelukast, a potent leukotriene receptor antagonist, causes dose-related improvements in chronic asthma. Montelukast Asthma Study Group
Authors: Noonan MJ , Chervinsky P , Brandon M , Zhang J , Kundu S , McBurney J , Reiss TF
Published: November 2002

The leukotrienes are known to be important mediators of bronchial asthma. The ability of montelukast, a potent and selective CysLT1 leukotriene receptor antagonist, to cause a dose-related improvement in chronic asthma was investigated in a placebo-controlled, multicentre, parallel-group study. After a two week placebo run-in period, chronic asthmatic patients with a forced expiratory volume in one second (FEV1) 40-80% predicted with > or = 15% increase (absolute value) after beta2-agonist were randomly assigned to one of four treatment groups (placebo or montelukast 2, 10, or 50 mg once daily in the evening) for a three week, double-blind treatment period. For patient-reported end-points (daytime symptom score, use of as needed inhaled beta2 agonist, asthma-specific quality of life) and frequency of asthma exacerbations, montelukast 10 and 50 mg caused similar responses, superior to 2 mg and significantly (p<0.05; linear trend test) different from placebo. All three doses caused improvements in FEV1 and morning and evening peak expiratory flow rate (PEFR) that were significantly (p<0.05) different from placebo. Differences (least square mean) between the pooled 10 and 50 mg montelukast treatment groups and placebo were: 7.1% change from baseline in FEV1, 19.23 L x min(-1) in morning PEFR, -0.29 in daytime asthma symptom score (absolute value), and -0.82 in beta2-agonist use (puff x day(-1)). The incidence of adverse experiences was neither dose-related nor different between montelukast and placebo treatments. We conclude that montelukast causes a dose-related improvement in patient-reported asthma end-points over the range 2-50 mg. Montelukast causes benefit to chronic asthmatic patients by improving asthma control end-points.
Effect of low-dose beclomethasone dipropionate on asthma control and airway inflammation
Authors: Fahy JV , Boushey HA
Published: November 2002

The effects of usual or low doses of inhaled corticosteroids on airway mucosal inflammation have not yet been examined. We therefore, compared the effects of inhaled beclomethasone dipropionate (BDP) 336 microg x day(-1) on asthma control outcomes and markers of airway inflammation. Twenty-four adult subjects with mild and moderate asthma were randomized to receive either BDP or placebo for four weeks; then subjects entered a single blind four week placebo run-in period. We found that the BDP group had significantly greater improvements in forced expiratory volume in one second (FEV1), morning peak flow, and rescue salbutamol use than the placebo-treated group. The improvement in FEV1 largely reversed one week after treatment was stopped. The decrease in the median percentage of eosinophils in induced sputum in the BDP group from 3.8% to 3.4% was not significant, but because eosinophils increased from 8.4% to 12.7% in the placebo group, there was a significant difference between treatment groups (p=0.03). There was no significant difference between groups during treatment in the levels of eosinophil cationic protein (ECP), tryptase mucin-like glycoprotein, or fibrinogen in induced sputum. The change in FEV1 in the BDP group did not correlate significantly with the change in eosinophil percentage or ECP levels. We concluded that four weeks of treatment with inhaled beclomethasone dipropionate 336 microg x day(-1) was associated with significant improvements in peak flow, forced expiratory volume in one second, and rescue salbutamol use in asthmatic subjects but was not associated with large reductions in markers of eosinophilic inflammation, bronchovascular permeability, or mucus hypersecretion.
Novel adaptation of a method to assess responsiveness of bronchial segments in vitro
Authors: Mc Parland BE , Johnson PR , Armour CL , Black JL
Published: November 2002

In vivo agonist delivery to the lungs is characterized by absorption through the mucosal layer followed by access to the smooth muscle. When agonists are applied to perfused bronchial segments, a difference in potency to agonists applied to the serosal (outside) or mucosal (inside) surface can be demonstrated. In order to elucidate this effect in canine bronchial segments, we adapted a method to assess responsiveness of agonists applied to the inside or outside surface of canine bronchial segments. A 2 cm "fluid-tight" length of bronchus was cannulated and mounted in a perfusion chamber. Auxotonic contraction of the bronchus displaced fluid inside the segment up a column and the change in height of fluid within the column (afterload) was measured as a change in hydrostatic pressure (volumetric). We assessed the optimal conditions for measuring bronchial responsiveness to acetylcholine. Neither stretching segments lengthways from 100 to 140% of resting length, nor altering the transmural pressure from 3 to 21 cmH2O had a significant effect on the potency of acetylcholine applied to the outside surface. Both acetylcholine (n=7) and methacholine (n=4) were approximately 10-fold more potent when applied to the outside surface than the inside surface of bronchial segments (p<0.0001). Furthermore, mechanical removal of the epithelium (n=6) led to a 67-fold increase in potency of acetylcholine applied to the inside surface compared with segments with epithelium. The advantages that this system has over previously reported methods include: 1) agonists can be injected at a low flow rate so as to minimize epithelial stress; 2) changes in luminal volume are measured under conditions of no flow; 3) after-load can be varied such that contraction is either practically isotonic or auxotonic; and 4) a "barrier effect" of the epithelium of canine bronchial segments can be demonstrated. This new adapted method will provide us with the means to assess the relationship between in vitro and in vivo responsiveness in human bronchi.
Upper airway cooling reduces upper airway resistance in anaesthetized young guinea-pigs
Authors: Curran AK , O'Halloran KD , Bradford A
Published: November 2002

In adults, the upper airway (UA) contains a variety of receptors including cold receptors, which evoke reflex effects on ventilation and UA dilator muscle activity, which may be important in the regulation of UA patency. However, very little is known about UA receptors in young animals, and the effects of UA cooling on UA dilator muscle activity and resistance have not been studied. A constant flow of warm or cool air was applied to the isolated UA in anaesthetized, vagotomized young guinea-pigs breathing spontaneously through a low-cervical tracheostomy while ventilation, UA resistance and geniohyoid muscle electromyographic activity were recorded. Cooling caused an inhibition of breathing, a reduction in UA resistance and an excitation of geniohyoid muscle activity. Topical anaesthesia of the UA or sealing the nose and cutting the superior laryngeal and glossopharyngeal nerves abolished the ventilatory and geniohyoid muscle responses but not the fall in UA resistance. It is concluded that upper airway cooling reflexly inhibits breathing and excites geniohyoid muscle activity. Cooling also reduces upper airway resistance by an effect which is not of reflex origin, possibly by reducing upper airway mucosal blood flow.
Specific immunotherapy downregulates peripheral blood CD4 and CD8 T-lymphocyte activation in grass pollen-sensitive asthma
Authors: Majori M , Bertacco S , Piccoli ML , Melej R , Pileggi V , Pesci A
Published: November 2002

Several lines of evidence indicate that specific immunotherapy may act by modifying the immune responses of T-lymphocytes to the antigen. To evaluate the effect of specific immunotherapy on the activation of T-lymphocytes by cluster of differentiation cells (CD4+ and CD8+) in peripheral blood, the expression of two surface activation markers, the p55 interleukin-2 receptor (CD25) and human leucocyte antigen (HLA)-DR, was studied prospectively on circulating CD4+ and CD8+ T-cell subsets in subjects with grass-pollen sensitive asthma before and after 1 yr of treatment with specific immunotherapy. Twenty five asthmatic patients with pollen sensitivity other than grass, studied out of their pollen season, served as the control group. Specific immunotherapy improved clinical indices of disease activity including symptom scores and medication use during the pollen season of the treatment year. It had a marked effect in reducing the expression of the two activation markers, CD25 and HLA-DR, in both CD4+ (p=0.002 and p=0.005, respectively) and CD8+ (p=0.01 and p=0.01, respectively) T-cell subsets, in parallel with a significant decrease in CD23 expression on B-cells (p=0.008) and in grass-specific immunoglobulin E levels (p=0.01) in the peripheral blood of subjects with grass pollen-sensitive asthma. The decreased T-lymphocyte activation observed in immunotherapy-treated subjects after the treatment year was significant (p=0.05) in comparison with the control group. These data add to the view that the efficacy of specific immunotherapy may be attributed to the downregulation of T-cell responses.
Effects of orally inhaled budesonide in seasonal allergic rhinitis
Authors: Greiff L , Andersson M , Svensson C , Linden M , Wollmer P , Brattsand R , Persson CG
Published: November 2002

It has previously been demonstrated that topical nasal treatment with glucocorticosteroids has significant effects on the bronchial airways. Less is known about effects on nasal disease by topical bronchial treatment with these drugs. The present study examined effects on nasal allergic disease of inhaled budesonide (avoiding nasal deposition of the drug). Patients with seasonal allergic rhinitis, but without asthma, were thus given inhalations of budesonide (600 microg b.i.d.) or placebo. The aim of the design was to allow the study of eosinophilic airway disease in a part of the airway other than the directly treated locus. Moderate to high birch pollen levels were recorded during the study season, and nasal symptoms were significantly increased in both treatment groups, although they were milder in patients receiving budesonide than in the placebo group (p<0.05). Nasal brush eosinophils and nasal lavage fluid levels of eosinophil cationic protein as well as blood eosinophils were increased during the season (p<0.05), but these increases were prevented by the inhaled budesonide. Nasal lavage fluid levels of alpha2-macroglobulin were particularly elevated in the placebo group but did not differ between patients receiving placebo and budesonide. Budesonide prevented the seasonal development of increased bronchoconstrictor responses to methacholine challenge (p<0.05). In conclusion, budesonide reduced the seasonal eosinophilia both in the circulation and in the nose along with an attenuation of seasonal nasal symptoms. Hence, at a daily dose of 600 microg b.i.d., known to cause no, or minimal, adverse effects, inhaled budesonide produces clinically significant anti-inflammatory effects in the entire airways, including the nasal mucosa, which is not exposed topically to the drug. We suggest that nasal and systemic anti-eosinophil actions are produced at commonly employed dose levels of orally inhaled budesonide.
Detection of immunoglobulins G and A to Aspergillus fumigatus by immunoblot analysis for monitoring Aspergillus-induced lung diseases
Authors: van Rens MT , Vernooy-Jeras R , Merton-de Ridder M , van Velzen-Blad H , van den Bosch JM
Published: November 2002

The aim of the study was to investigate whether patients with Aspergillus-induced lung disease can be monitored by immunoblot analysis to detect antibodies to Aspergillus fumigatus (Af). Immunoblotting was performed by incubating 57 longitudinally collected sera from 13 patients on nitrocellulose sheets, blotted with Af antigen, separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Bound antibodies were demonstrated by peroxidase-labelled antihuman immunoglobulins (Ig)G and IgA antiserum and diaminobenzidine plus H2O2 as substrate. The immunoblot patterns were related to the patients' clinical status and time. Each patient had a characteristic immunoblot pattern that varied with time. There was a relationship between disease activity or clinical response and changes in immunoblot antibody patterns: a rise in anti-Af IgG and IgA antibodies was seen in sera collected during active disease, compared with before active disease, and a significant decline in anti-Af IgG and IgA was demonstrated in sera collected during recovery, compared with during active disease. Only in the acute stage of allergic bronchopulmonary aspergillosis were IgA antibodies against Af antigens of <20,000 Da demonstrated. Immunoblot analysis can be used to monitor the disease activity and the responses to treatment of patients with Aspergillus-induced lung diseases. Changes in specific immunoglobulin A may be more informative than specific immunoglobulin G.
Role of interleukin-2 in the development and persistence of lymphocytic alveolitis in farmer's lung
Authors: Dakhama A , Israel-Assayag E , Cormier Y
Published: November 2002

Farmer's lung (FL) is characterized by an intense lymphocytic alveolitis which persists after an acute episode with continuous exposure to the offending antigens. This study aimed to examine the role of interleukin-2 (IL-2) in the development and persistence of this lymphocytic alveolitis. Three groups of dairy farmers were studied: acute FL, ex-FL (past history of FL but no clinical evidence of active disease) and asymptomatic farmers (no lung disease). IL-2 was measured by enzyme immunosorbent assay and T-cell proliferation was evaluated by 3H-thymidine incorporation. Acute and ex-FL patients had more lymphocytes (p<0.01) and higher levels of IL-2 (p<0.05) in their bronchoalveolar lavage (BAL) than asymptomatic farmers. BAL T-lymphocytes from acute and ex-FL patients released considerable amounts of IL-2 after stimulation with concanavalin A and showed dose-dependent proliferative responses to IL-2. IL-2 production was decreased after treatment with prednisone. Acute FL patients, but not ex-FL, had higher levels of soluble CD25 in their serum than asymptomatics (p=0.009). These results suggest that interleukin-2 may play a role in farmer's lung by providing a stimulus not only for the accumulation of lymphocytes but also for their persistence at the site of hypersensitivity reaction, and that the lung is a likely source of this cytokine in vivo.
Six year longitudinal study of respiratory function in dairy farmers in the Doubs province
Authors: Dalphin JC , Maheu MF , Dussaucy A , Pernet D , Polio JC , Dubiez A , Laplante JJ , Depierre A
Published: November 2002

A previous study, carried out in 1986 in France, showed the prevalence of respiratory symptoms and of respiratory function impairment to be higher in dairy farmers than in a control group of nonexposed subjects living in a rural zone. In order to confirm the harmful effect of dairy farming, the two groups were re-studied 6 yrs later at the same period of the year. One hundred and ninety-four (77.6%) farmers and 155 (62%) control subjects were available for re-examination. Non-re-evaluated subjects were comparable to re-evaluated subjects for age, sex, smoking and respiratory symptoms and function at initial evaluation. Dairy farmers consistently had more respiratory symptoms and lower levels of respiratory function than did control subjects. In the study populations as a whole, the mean annual decline in vital capacity (VC) and forced expiratory volume in one second (FEV1) was slightly, but nonsignificantly, higher in farmers than in control subjects: in mL x yr(-1) (SD), -43.1 (68.2) versus -37.9 (60.2) for VC and -32.8 (56.7) versus -30 (47.2) for FEV1. There was a positive interaction between farming and age (i.e. duration of exposure in this cohort) on respiratory function decline, and in male subjects aged > or = 45 yrs, dairy farming was associated with an accelerated loss in VC (p<0.05) and FEV1 (p<0.05) after controlling for age, smoking, height and geographic location in a multiple linear regression model. Initial values of respiratory function, age and pack-years smoked (only for VC) were the other variables found to be significant determinants of decline in lung function. In conclusion, this study mainly suggests that dairy farming is associated to a very moderate accelerated loss in respiratory function that increases with duration of exposure and is significant in older male subjects.
Effects of 0.2 ppm ozone on biomarkers of inflammation in bronchoalveolar lavage fluid and bronchial mucosa of healthy subjects
Authors: Krishna MT , Madden J , Teran LM , Biscione GL , Lau LC , Withers NJ , Sandstrom T , Mudway I , Kelly FJ , Walls A , Frew AJ , Holgate ST
Published: November 2002

Short-term exposure to ozone at peak ambient levels induces neutrophil influx and impairs lung function in healthy humans. In order to investigate the mechanisms contributing to neutrophil recruitment and to examine the role of T-cells in the acute inflammatory response, we exposed 12 healthy humans to 0.2 parts per million (ppm) of ozone and filtered air on two separate occasions for 2 h with intermittent periods of rest and exercise (minute ventilation = 30 L x min(-1)). Fibreoptic bronchoscopy was performed 6 h after the end of exposures. Total protein, tryptase, histamine, myeloperoxidase, interleukin (IL)-8 and growth-related oncogene-alpha (Gro-alpha) were measured and total and differential cell counts were performed in bronchoalveolar lavage (BAL) fluid. Flow cytometry was performed on BAL cells to study total T-cells, T-cell receptors (alphabeta and gammadelta), T-cell subsets (CD4+ and CD8+ cells) and activated T-cell subsets (CD25+). Using immunohistochemistry, neutrophils, mast cells, total T-cell numbers, T-cell subsets, CD25+ T-cells and leukocyte endothelial adhesion molecules including P-selectin, E-selectin, intercellular adhesion molecule (ICAM)-1 and vascular adhesion molecule (VCAM)-1 were quantified in the bronchial biopsies. Paired samples were available from nine subjects. Following ozone exposure there was a threefold increase in the proportion of polymorphonuclear neutrophils (PMNs) (p=0.07) and epithelial cells (p=0.05) in BAL fluid. This was accompanied by increased concentrations of IL-8 (p=0.01), Gro-alpha (p=0.05) and total protein (p=0.058). A significant positive correlation was demonstrated between the two chemokines and proportion of PMNs in BAL fluid. After ozone exposure there was a significant decrease in the CD4/CD8 ratio (p=0.05) and the proportion of activated CD4+ (p=0.01) and CD8+ T-cells (p=0.04). However, no significant changes were demonstrable in any of the inflammatory markers studied in the biopsies. Short-term exposure of healthy humans to 0.2 ppm ozone induced a neutrophil influx in peripheral airways at 6 h post exposure, but no apparent inflammatory response in proximal airways. This response seems to be mediated at least in part by interleukin-8 and growth-related oncogene-alpha.
Acid fog and hospital visits for asthma: an epidemiological study
Authors: Tanaka H , Honma S , Nishi M , Igarashi T , Teramoto S , Nishio F , Abe S
Published: November 2002

The aim of this study was to elucidate the adverse respiratory effects of naturally occurring acid fog. In total, 102 adult asthmatic patients (44 nonatopic and 58 atopic) were studied for a 2 yr period (January 1992 to December 1993) in Kushiro, a city with only a small industrial area, located in the northern-most island in Japan. Fog occurred on 378 out of 731 days, and the acidity of the fog ranged from pH 3.32 to 6.91 (mean pH 4.95). The association between hospital visits for asthma and meteorological factors or air pollutants was investigated. In nonatopic patients, fog, high ozone and water vapour pressure, low day-to-day temperature differences, low concentrations of atmospheric NO and NO2 contributed significantly (p<0.05) to increasing hospital visits. In atopic subjects, fog, high water vapour pressure, low levels of atmospheric NO2 and SO2 contributed significantly to hospital visits (p<0.05). In Poisson regression analysis the remaining factors of significance (p<0.01) for nonatopic asthma were fog and low NO and for atopic asthma were high water vapour pressure and low SO2 (p<0.05). A weak but significant correlation was observed between the number of hospital visits and the mean pH of the foggy day (r=-0.38, p<0.05) in nonatopic asthmatic patients, not in atopic asthma. On foggy days, gaseous air pollutant levels were significantly (p<0.01) lower than on fog-free days. It was concluded that, naturally occurring acid fog may have a weak bronchoconstrictive effect which appears to be more influential in nonatopic asthmatic subjects than in atopic subjects.
Association between PM10 and decrements in peak expiratory flow rates in children: reanalysis of data from five panel studies
Authors: Hoek G , Dockery DW , Pope A , Neas L , Roemer W , Brunekreef B
Published: November 2002

Panel studies have found 1-3% increases in reports of acute respiratory symptoms associated with each 10 microg x m(-3) increase in ambient concentrations of particles with a 50% cut-off aerodynamic diameter of 10 microm (PM10). Statistically significant decrements in population mean peak expiratory flow (PEF) have also been observed but their magnitude is only about 0.1% for the same exposure. This study evaluated whether this difference is due to the different measurement scales used for the expression of the effects of air pollution on PEF and respiratory symptoms. The association between the prevalence of large decrements in PEF (more than 10% or 20% below the median) and PM10 concentrations was analysed using data from five recent panel studies. The effect estimates were compared to the effect estimates from original studies based on the population mean PEF. The decrement in the population mean PEF for an increase of 10 microg x m(-3) of the same-day PM10 concentration was 0.07%, averaged over all panels. A significant relative increase of 2.7% (95% confidence interval 1.6-3.8) in the prevalence of PEF decrements greater than 10% was associated with the same exposure. In conclusion, defining the peak expiratory flow response by the prevalence of large decrements provides effect estimates of a comparable magnitude to effect estimates for the prevalence of reports of acute lower respiratory symptoms.
Effect of environmental tobacco smoke on cough in children with a history of tonsillectomy or adenoidectomy
Authors: Chen Y , Rennie DC , Lockinger LA , Dosman JA
Published: November 2002

We examined the possible impact of tonsillectomy or adenoidectomy (T/A) on the relationship between environmental tobacco smoke (ETS) exposure and respiratory outcomes. This study was conducted in Humboldt, Saskatchewan, in 1993. The target population included all residents aged 6-17 yrs. Of the 1,019 eligible subjects, 892 participated (88%). Estimates of ETS exposure were based on the reported smoking habits of the children's household members. We defined current cough as a positive response to the question: "Does this child usually have a cough?". Information also included morning cough, night cough and a history of T/A. For children with no history of T/A, the prevalence of current cough was 8.9%, 12.2% and 14.5% for those living in families with 0, 1, and 2+ smokers respectively. The corresponding prevalence was 7.0%, 30.2% and 36.8% for children with history of T/A. Similar effects of ETS exposure were observed on morning cough and night cough. The results did not change significantly when we used various ETS measures and controlled for confounding factors. Compared to children living in nonsmoking families and without history of T/A, the adjusted odds ratio for children with a history of T/A was 7.19 (p<0.001) if they were living in families smoking >20 cigarettes x day(-1) at home. The corresponding odds ratio was only 1.64 (p=0.11) for children without a history of T/A. We concluded that children living in smoking family were more likely to cough than those living in nonsmoking families and tonsillectomy or adenoidectomy increased the apparent influence of environmental tobacco exposure on cough.
Increasing prevalence of wheeze and asthma in Nottingham primary schoolchildren 1988-1995
Authors: Venn A , Lewis S , Cooper M , Hill J , Britton J
Published: November 2002

The prevalence of asthma in children has increased substantially in many countries in recent decades, but it is not clear how much this trend has continued into the 1990s. This study aimed to estimate the current prevalence of asthma and wheeze in British primary schoolchildren and to determine whether there has been any increase in the prevalence of these conditions since 1988. The prevalence of self-reported wheeze and asthma was measured by parental questionnaire in 22,968 children aged 4-11 yrs attending primary schools in the Nottingham area of England in 1995, and these estimates were compared with data from a subsample of the same schools in 1988. In 1995, wheezing ever was reported in 24.0% of children, wheezing in the past year in 15.1% and diagnosed asthma symptomatic in the past year in 8.8%. All measures have increased in prevalence since 1988, in absolute terms by 7.7% for wheeze ever, by 2.6% for wheeze in the past year and by 2.7% for asthma. The increases were greater in females than males, but did not vary with age. In conclusion, the prevalence of asthma has continued to rise in British schoolchildren since the late 1980s, particularly in females, and across all ages.
Expression of insulin-like growth factors and their binding proteins by bronchoalveolar cells from children with and without interstitial lung disease
Authors: Chadelat K , Boule M , Corroyer S , Fauroux B , Delaisi B , Tournier G , Clement A
Published: November 2002

The involvement of the insulin-like growth factor (IGF) system in lung growth and repair following injury is sustained by a number of studies. Based on this knowledge, the aim of the present work was to document the expression of the IGFs and their binding proteins by alveolar cells obtained by bronchoalveolar lavage (BAL). Two groups were investigated: a control group of five children and a group of 11 children referred to the department for exploration of interstitial lung disease (ILD). Components of the IGF system studied included IGF-I, IGF-II and IGF-binding proteins (IGFBP). Expression of these factors was analysed at the level of messenger ribonucleic acid (mRNA) (by semi-quantitative reverse transcription polymerase chain reaction techniques), and of protein for the IGFBPs. In addition, expression of two major cytokines associated with the inflammatory process, tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta), was also documented. In children without parenchymal disease, the growth factor expressed was IGF-I, in association with the presence of mRNA for IGFBP-2 in all cases. In children with ILD, expression of IGF-I was observed in nine patients and of IGF-II in three patients, and the presence of IGFBP-2 was found in all extracts analysed (mRNA and proteins). Evaluation of IGFBP-2 expression indicated an increase in the group of children with ILD. Interestingly, a significant association was observed between the increase in IGFBP-2 expression and TGF-beta expression. The present data emphasize the presence on insulin-like growth factor-binding protein-2 in the BAL of all patients, and suggest that this protein may be an important factor of the injury/repair processes during the progression of alveolar inflammation.
Effects of formoterol, salmeterol or oxitropium bromide on airway responses to salbutamol in COPD
Authors: Cazzola M , Di Perna F , Noschese P , Vinciguerra A , Calderaro F , Girbino G , Matera MG
Published: November 2002

We examined whether a pretreatment with formoterol, oxitropium bromide, or salmeterol might modify the dose-response curves to inhaled salbutamol in patients with stable and partially reversible chronic obstructive pulmonary disease (COPD). Sixteen outpatients with partially reversible, stable COPD received 24 microg formoterol, 50 microg salmeterol, 200 microg oxitropium bromide, or placebo on four non-consecutive days. Spirometric testing was performed immediately before inhalation of treatment and after 2 h. A dose-response curve to inhaled salbutamol was then constructed using doses of 100, 100, 200 microg and 400 microg--that is, a total cumulative dose of 800 microg. Dose increments were given at 20 min intervals with measurements being made 15 min after each dose. Formoterol, salmeterol, or oxitropium bromide elicited a significant increase in forced expiratory volume in one second (FEV1) compared with placebo (mean differences (L) = placebo 0.05; formoterol 0.34; salmeterol 0.27; oxitropium bromide 0.23). Dose-dependent increases in FEV1 were seen (mean values (L) before salbutamol and after a cumulative dose of 100, 200, 400, and 800 microg = placebo: 1.06, 1.28, 1.35, 1.39, 1.41; formoterol: 1.33, 1.37, 1.41, 1.44, 1.44; salmeterol: 1.30, 1.33, 1.36, 1.39, 1.42; oxitropium bromide: 1.27, 1.34, 1.37, 1.41, 1.40). Statistical analysis revealed no significant differences in FEV1 and forced vital capacity (FVC) responses to salbutamol after therapy with formoterol, salmeterol, or oxitropium bromide compared with placebo. This study clearly shows that a pretreatment with a conventional dose of formoterol, salmeterol, or oxitropium bromide does not preclude the possibility of inducing a further bronchodilation with salbutamol in patients suffering from partially reversible chronic obstructive pulmonary disease.