| 1. |
- Ekberg-Jansson, Ann, et al.
(författare)
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Neutrophil-associated activation markers in healthy smokers relates to a fall in DL(CO) and to emphysematous changes on high resolution CT
- 2001
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 95:5, s. 363-373
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Tidskriftsartikel (refereegranskat)abstract
- Smoking is a risk factor for developing chronic obstructive pulmonary disease (COPD), but there are no good indicators for early identification of subjects who will develop symptomatic COPD. The aim of this study was to investigate inflammatory mechanisms related to changes in lung function and emphysematous changes on high resolution computed tomography (HRCT) in 'healthy' smokers. Subjects were 60-year-old men from a population study. Bronchoscopy was performed in 30 smokers and 18 who had never smoked. Blood tests, lung function measurements and HRCT were carried out in 58 and 34 subjects, respectively. In comparison with never-smokers, smokers had higher levels of myeloperoxidase (MPO), human neutrophil lipocalin (HNL), eosinophil cationic protein (ECP) and lysozyme in blood, higher levels of MPO, interleukin-8 (IL-8) and HNL in bronchial lavage (BL), and of IL-8, HNL and interleukin-lbeta (IL-1beta) in bronchoalveolar lavage (BAL). Smokers also had lower levels of Clara cell protein 16 (CC-16) in blood. HNL in BL and BAL showed strong correlations to other inflammatory markers (MPO, IL-8, IL-1beta). The variations in MPO in BL were explained by variations in HNL (R2 =0.69), while these variations in BAL were explained by variations in HNL and IL-1beta (R2 = 0.76). DL(CO) was the lung function variable most closely related to MPO and IL-8 in BL and BAL and to IL-1beta in BAL. In a multiple regression analysis, MPO, IL-1beta, IL-8 and CC-16 in BL and MPO in BAL contributed to the explanation of variations in DL(CO) to 41% and 22%. respectively, independent of smoking habits. In smokers with emphysematous lesions on HRCT, HNL in BAL correlated to emphysema score (r(s) = 0.71). We conclude that 'healthy' smoking men with a near normal FEV1 show signs of inflammation in the lower airways that are related to a decrease in DL(CO) and to emphysematous lesions on HRCT. This inflammation seems to be the result of both monocyte/macrophage and neutrophil activation.
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| 2. |
- Ekberg-Jansson, A, et al.
(författare)
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Respiratory symptoms relate to physiological changes and inflammatory markers reflecting central but not peripheral airways. A study in 60-year-old 'healthy' smokers and never-smokers
- 2001
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 95:1, s. 40-47
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the relationship between respiratory symptoms, lung function and inflammatory markers in 'healthy' smokers. The study population was recruited from an epidemiological study with subjects of the same age, 60 years. Only smokers who considered themselves healthy (n=58) and a random sample of never-smokers (n=34) were investigated. All subjects underwent lung function tests--spirometry, carbon monoxide transfer (DLco) and the single-breath N2 method (N2 test)--together with high-resolution computed tomography (HRCT). A flexible bronchoscopy with a bronchoalveolar lavage (BAL) was performed in 30 smokers and 18 never-smokers. Bronchial biopsies were also taken. Smokers who reported non-specific respiratory problems, chronic bronchitis and wheezing in a symptom questionnaire had a lower forced expiratory volume in 1 sec (FEV1), FEV% and specific airway conductance (sGaw), lung function tests supposed to reflect the more central airways, than smokers without respiratory symptoms. A limited number of smokers with occasional non-specific respiratory problems also had more cytotoxic T cells (CD8) in bronchial biopsies. No differences were found in DLCO and the N2 test, lung function tests supposed to reflect the more peripheral airways including the alveoli, HRCT-diagnosed emphysema or inflammatory markers in blood and BAL between smokers with and without respiratory symptoms. It is concluded that even when smokers consider themselves 'healthy' they have mild symptoms that are related more to physiological changes and inflammatory markers that may reflect events in the central airways than to changes that may reflect events in the peripheral airways.
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| 3. |
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| 4. |
- Jacobson, L, et al.
(författare)
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The economic impact of asthma and chronic obstructive pulmonary disease (COPD) in Sweden in 1980 and 1991
- 2000
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 94:3, s. 247-255
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Tidskriftsartikel (refereegranskat)abstract
- This study was carried out to estimate the direct and indirect costs associated with asthma and chronic obstructive pulmonary disease (COPD) in Sweden in 1980 and 1991, and to identify trends in the use of outpatient care, drugs and inpatient care, and the development of temporary morbidity, permanent disability and mortality for asthma and COPD. Routinely published administrative and population data were used to estimate the costs of asthma and COPD, and these figures were compared to corresponding estimates and trends for all respiratory diseases as well as for all diseases. Asthma and COPD each accounted for about SEK 3 billion, together roughly 2% of the economic cost of all diseases. Although the total costs associated with each disease were similar, the distribution of the different cost components and changes in each component over time differed. During the 1980s, the cost of drugs and out-patient care increased for both diseases. The cost of inpatient care for asthma decreased, whereas that for COPD increased. This study shows that asthma therapy has changed from inpatient to ambulatory care in Sweden, while the treatment of COPD to a higher degree still is based on inpatient care.
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| 5. |
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| 6. |
- Arakawa, H, et al.
(författare)
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Airway responses following intradermal sensitization to different types of allergens: ovalbumin, trimellitic anhydride and Dermatophagoides farinae
- 1995
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Ingår i: International Archives of Allergy and Immunology. - 1423-0097. ; 108:3, s. 274-280
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Tidskriftsartikel (refereegranskat)abstract
- Sensitization of guinea pigs by intradermal injections of the occupational allergen trimellitic anhydride (TMA) in oily vehicle has been shown to be very reproducible. We studied the effect of intradermal sensitization with ovalbumin (OA) in oily vehicle on immune and airway responses in guinea pigs. We also compared airway responses to trimellitic anhydride or Dermatophagoides farinae (DF; mite) with those to OA in guinea pigs intradermally sensitized to respective allergens. Three to four weeks after sensitization, the animals were challenged with intratracheal instillation of these allergens. Intradermal injections with OA developed dose-dependently specific IgG1 antibodies to OA demonstrated by ELISA. In animals sensitized with different doses of OA in corn oil vehicle, a challenge with OA induced a reversely dose-dependent airflow obstruction and airway plasma exudation. In contrast, animals sensitized with OA in saline vehicle had dose-dependent airway responses to OA. Challenge with OA caused an immediate peak and subsequently persistent airflow obstruction, whereas this response to either TMA guinea pig serum albumin or Df was slowly progressive in animals sensitized to respective allergens. The animals sensitized to TMA or Df may show a different profile of airway responses following the challenge compared to OA. Intradermal sensitization may be a valuable method of sensitization for the development of an animal model of airway allergy to different types of allergens, including chemicals or mites.
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| 7. |
- Arakawa, H, et al.
(författare)
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Effect of maturation on airway plasma exudation induced by eicosanoids in guinea pig
- 1994
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Ingår i: European Journal of Pharmacology. - 1879-0712. ; 259:3, s. 251-257
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Tidskriftsartikel (refereegranskat)abstract
- Airway reactivity to bronchoconstrictor mediators changes with age. We studied the effects of maturational change on airway responses induced by a thromboxane A2 mimetic, U-46619 (2, 6 and 20 nmol/kg; i.v.), leukotriene D4 (0.6 and 2 nmol/kg; i.v.) or vehicle (0.9% NaCl; i.v.) in immature (196 +/- 3 g: 2 weeks) and adult guinea pigs (512 +/- 5 g: 11 weeks). In the same animals, we measured both lung resistance (RL) to monitor airflow obstruction and extravasation of Evans Blue dye (20 mg/kg) to quantify airway plasma exudation. For a comparison, changes in RL in response to acetylcholine (5, 15 and 50 nmol/kg; i.v.) were also examined in both age groups. The order of potency to induce an increase in RL did not change with age (leukotriene D4 > U-46619 > acetylcholine). In immature animals, the peak RL after U-46619 (2, 6 and 20 nmol/kg; P < 0.05, P < 0.005 and P < 0.01, respectively) and leukotriene D4 (2 nmol/kg; P < 0.01) was significantly higher than in adult animals. U-46619 and leukotriene D4 produced significant extravasation of Evans Blue dye in both immature and adult animals. The order of potency to induce extravasated dye also did not change with age (leukotriene D4 > U-46619). The amount of extravasation of Evans Blue dye after U-46619 (6 and 20 nmol/kg) and leukotriene D4 (0.6 and 2 nmol/kg) was significantly smaller in immature animals than adults at all airway levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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| 8. |
- Arvidsson, P, et al.
(författare)
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Exudation of plasma and production of thromboxane in human bronchi after local bradykinin challenge
- 2001
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 95:5, s. 313-318
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Tidskriftsartikel (refereegranskat)abstract
- Plasma exudation has been suggested to be an important component of the inflammatory response in asthma. Bradykinin elicits many of the features of asthma, including bronchoconstriction, cough, plasma exudation and mucus secretion. In an attempt to quantify local plasma exudation, we have employed a novel low-trauma technique with the aim of challenging and lavaging a central part of the bronchial tree, by selecting a medium sized bronchus. A fibreoptic bronchoscopy was performed in non-smoking healthy volunteers. The instrument was placed proximally in the right upper lobe bronchus. A plastic catheter, equipped with an inflatable latex balloon, was inflated with air (2-4 cmH2O). A solution (100 microl of either two different concentrations of bradykinin: 0.09 and 0.9 mg ml(-1) or normal saline) was instilled through the catheter and distal to the balloon. Eight minutes later a lavage procedure with 10 ml of saline was performed through the catheter. The procedure was then repeated twice, with the other solutions, but from the lingular and middle lobe bronchi. All solutions were given in a blinded fashion, and two different studies were performed. Lavage concentrations of albumin and IgG were quantified as measurements of plasma exudation. In our first study we found that bradykinin challenge significantly increased concentrations of albumin and IgG. In study two, there was no numeric increase in plasma proteins after local bradykinin challenge, but the concentration of thromboxane was significantly increased in lavages from bradykinin-challenged bronchi. Thus, local bronchial administration of bradykinin has the capacity to induce exudation of large plasma macromolecules into the bronchial lumen, as well as local thromboxane production.
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| 9. |
- Bergendal, A, et al.
(författare)
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Extent of salmeterol-mediated reassertion of relaxation in guinea-pig trachea pretreated with aliphatic side chain structural analogues
- 1996
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Ingår i: British Journal of Pharmacology. - 1476-5381. ; 117:6, s. 1009-1015
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Tidskriftsartikel (refereegranskat)abstract
- 1. Salmeterol is a potent, selective and long acting beta 2-adrenoceptor agonist. In vitro, salmeterol exerts 'reassertion' relaxation of airways smooth muscle. Reassertion relaxation refers to the capacity of salmeterol to cause repeated functional antagonism of induced contraction when airway smooth muscle is intermittently exposed to, then washed free from, beta-adrenoceptor antagonists such as sotalol. The mechanism(s) underlying reassertion relaxation are unknown but may relate to high affinity binding of the long aliphatic side chain of salmeterol to an accessory site, distinct from the agonist recognition site, in or near the beta 2-adrenoceptor (exosite binding hypothesis). 2. In order to test the exosite hypothesis, three pure analogues of salmeterol, each exactly preserving the molecular structure of the aliphatic side chain but with zero or low efficacy at the beta 2-adrenoceptor were synthesized. The effect of pre-incubating guinea-pig tracheal smooth muscle with these analogues on salmeterol-induced reassertion relaxation was determined. 3. Computer Assisted Molecular Modelling of these molecules revealed that each of them exactly preserved the low energy linear conformation of the aliphatic side chain of salmeterol. Measurement of lipophilicity (octanol:water partition coefficient; log P) and direct partition into synthetic membranes (membrane partition coefficient; Kpmem) showed that all compounds had high affinity for lipids and membranes. In particular the biophysical properties of CGP 59162 (log P 1.89, Kpmem 16500) were very similar to salmeterol (log P 1.73, Kpmem 16800). 4. Two of the analogues, CGP 54103 and D 2543 (1 microM), which are structural mimics of the side chain of salmeterol, differing slightly in their length, did not prevent either the initial relaxation induced by salmeterol (0.1 microM) or the reassertion relaxation; however, it was not possible to determine whether either of these molecules occupied the beta 2-adrenoceptor. 5. The third analogue, CGP 59162, which has the substituents on the active saligenin head group of salmeterol in transposed positions, itself exerted a weak beta 2-adrenoceptor-mediated relaxation antagonized by ICI 118551 (beta 2-selective antagonist) but not CGP 20712 (beta 1-selective antagonist) and, at higher concentrations CGP 59162 caused reassertion relaxation suggesting that it may occupy and activate the beta 2-adrenoceptor in a manner analogous to salmeterol. 6. CGP 59162, at concentrations up to ten fold molar excess, did not prevent or reduce salmeterol-induced reassertion relaxation. 7. In conclusion these data are not consistent with the existence of a distinct 'exosite' recognising the aliphatic side chain of salmeterol mediating reassertion.
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| 10. |
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| 11. |
- Michaloski, John, et al.
(författare)
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Push–Button Discrete Event Simulation for Analysis of Factory Floor Operations
- 2010
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Ingår i: ASME 2010 International Mechanical Engineering Congress and Exposition, IMECE 2010; Vancouver, BC; Canada; 12 November 2010 through 18 November 2010. - 9780791844274 ; 3:PARTS A AND B, s. 313-319
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Konferensbidrag (refereegranskat)abstract
- In manufacturing, Discrete Event Simulation (DES) can beeffectively used to model production and provide sustainability analysis of equipment and system operation by measuring throughput, capacity, and bottlenecks. DES allows analysis under different scenarios and conditions that can then be used to forecast more optimal system performance. For discrete parts production, DES is rarely used because of the difficulty in attaining timely and accurate statistical modeling of the equipment and process operation. In this paper we look at the use of the plant floor interoperability standard, MTConnect, as a means to improve the access to machine tool data. Given data access, we develop a Finite State Model in order to streamline Machine Tool and DES integration. A case study of a prototype Capacity Planning system using DES as a modeling back–end will be described to help in understanding resource allocation of shop floor machines to a batch of aerospace parts. Direct machine tool statistical parameterization into a Web–based DES leads to “Push–button” automated simulations.
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| 12. |
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| 13. |
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| 15. |
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| 16. |
- Ställberg, Björn, et al.
(författare)
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Potency ratio fluticasone propionate (Flixotide Diskus)/budesonide (Pulmicort Turbuhaler)
- 2007
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Ingår i: Respir Med. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 101:3, s. 610-5
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Tidskriftsartikel (refereegranskat)abstract
- In the choice of, or switch between, various inhaled corticosteroids (ICS) it is important to know equipotent doses for clinical treatment effects of the alternatives. Various ICS do have different inherent potency. Further, the ICS are delivered from inhalers that may differ markedly in output characteristics and drug delivery to intrapulmonary airways. Therefore, clinical efficacy comparisons must include drug-inhaler comparisons. We estimated the therapeutic potency ratio of the Flixotide Diskus (fluticasone propionate, FP) and the Pulmicort Turbuhaler (budesonide, BUD) in steroid-naive asthma patients, using a dose-reduction technique (FP 500-0 mcg/day, BUD 800-0 mcg/day). The dose defining end point was loss of asthma control in this paper denoted as exacerbation. In total, 282 patients with proven asthma were enrolled in the study, and 103 in the FP group and 98 in the BUD group completed the study per protocol. In total, 80 patients in the FP-group and 79 in the BUD-group experienced a dose defining exacerbation. The exacerbation frequency increased in a dose-dependent way as the dose was titrated down. From these data the potency difference between the present drug inhaler combinations, Flixotide Diskus and Pulmicort Turbuhaler, was calculated to be between 1.50:1 (95% CI 1.10:1-2.05:1) and 1.75:1 (CI 1.26:1-2.43:1) depending on if patients with insufficient steroid-response were excluded from the calculations or not. In these steroid-naive patients, the potency difference was evident only at low daily doses, below 200 mcg.
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| 17. |
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| 18. |
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