| 1. |
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| 2. |
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| 3. |
- Löfdahl, Magnus J, et al.
(författare)
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Increased intraepithelial T-cells in stable COPD
- 2008
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 102:12, s. 1812-1818
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The airway epithelium is the first line of defence in the response to inhaled particles and irritants. Chronic obstructive pulmonary disease (COPD) is an inflammatory disease characterised by an irreversible loss of lung function, with cigarette smoking as a major risk factor. Here, we address intraepithelial T-cells in COPD, as these cells are a distinct T-cell subtype thought to have important regulatory functions. We hypothesised that intraepithelial T-cells play a role in the response to lung irritants and that the T-cell populations would be altered and associated with signs of inflammation in COPD. METHODS: Bronchoscopy with endobronchial mucosal biopsy sampling was performed in 22 patients (mean age; 57) with stable COPD (median FEV(1)% predicted: 51). Age- and smoking- matched smokers (S) with normal lung function (n=14) and age-matched non-smokers (NS) (n=15) served as controls. Airway inflammation was recorded visually using bronchitis index (BI). Biopsy specimens were processed into glycol methacrylate resin and inflammatory cells were stained immunohistochemically. RESULTS: The number of intraepithelial CD4+ T-cells were significantly higher in COPD patients compared to smokers as well as trend towards significance in non-smokers (p=0.005 and p=0.036, respectively), whereas intraepithelial CD8+ T-cells number were increased in patients with COPD compared to non-smokers (p=0.017). Both patients with COPD and smokers had a higher BI than non-smokers (p<0.001 for both). CONCLUSIONS: The present data suggest a role for intraepithelial CD4+ and CD8+ T-cells in stable COPD and indicate that T-cells are of importance in the long-term inflammatory response in COPD or, alternatively, play a regulatory role.
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| 4. |
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| 5. |
- Al-Shamkhi, Nasrin, et al.
(författare)
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Important non-disease-related determinants of exhaled nitric oxide levels in mild asthma – results from the Swedish GA2LEN study
- 2016
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 46:9, s. 1185-1193
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fractional exhaled nitric oxide (FeNO) has a potential clinical role in asthma management. Constitutive factors such as age, height and gender, as well as individual characteristics, such as IgE sensitization and smoking, affect the levels of FeNO in population-based studies. However, their effect on FeNO in subjects with asthma has been scarcely studied. Objective: To study the effects on FeNO of these commonly regarded determinants, as demonstrated in healthy subjects, as well as menarche age and parental smoking, in a population of asthmatics. Material and Methods: Fractional exhaled nitric oxide was measured in 557 subjects with asthma from the Swedish GA2LEN study. Allergic sensitization was assessed by skin prick tests to most common aeroallergens. Upper airway comorbidities, smoking habits, smoking exposure during childhood and hormonal status (for women) were questionnaire-assessed. Results: Male gender (P < 0.001), greater height (P < 0.001) and sensitization to both perennial allergens and pollen (P < 0.001) are related to higher FeNO levels. Current smoking (P < 0.001) and having both parents smoking during childhood, vs. having neither (P < 0.001) or only one parent smoking (P = 0.002), are related to lower FeNO. Women with menarche between 9 and 11 years of age had lower FeNO than those with menarche between 12 and 14 years of age (P = 0.03) or 15 and 17 years of age (P = 0.003). Conclusions and Clinical relevance: Interpreting FeNO levels in clinical practice is complex, and constitutional determinants, as well as smoking and IgE sensitisation, are of importance in asthmatic subjects and should be accounted for when interpreting FeNO levels. Furthermore, menarche age and parental smoking during childhood and their effects on lowering FeNO deserve further studies. © 2016 John Wiley & Sons Ltd
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| 6. |
- Asplund, Erik, et al.
(författare)
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Framsyn för Norrbotten och Västerbotten : en idéskrift om utvecklingsinsatser idag och imorgon
- 2009
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Rapport från DARE delprojekt regional framsyn. Etapp 1; scenarier och förslag på aktiviteter.Detta dokument är slutrapporten från den regionala framsynsprocessen som drevs 2008-2009 inom projektet DARE – Development Arena for Research and Entrepreneurship.Framsynen har verkat efter ett normativt och handlingsinriktat angreppssätt. Ledmotiv för processen har varit frågor som: Hur vill vi ha det? Varför är det inte så nu? Vad behöver vi göra nu och i framtiden? Regionen kan sägas kännetecknas av att den är rik på naturresurser och fattig på folk. Det är bakgrunden till de fokusområden som framsynen behandlat- Grönare näringsliv (hur kan nya och miljöeffektivare produkter och tjänsterutvecklas effektivare?)- Demografiutveckling (hur kan samhällsfunktionerna bestå med inverteradebefolkningspyramider och hur kan utvecklingen mot en åldrande befolkningvändas?)Lite tvärs över båda frågorna ovan hamnar ett annat fokus; regionens attraktivitet. Inom detta område har en ung framsyn genomförts med deltagare från olika delar av Norrbotten.Framsynen har gått steg för steg genom visioner, analys av framgångsfaktorer, scenarieskapande, förslag på åtgärder och prioritering av dessa. Under genomförandet har det uppstått ett antal avknoppningar i form av t ex nya samarbeten och projekt. Ett av de sistnämnda var den unga framsynen som genomfördes med finansiering av Norrbottens läns landsting.Bland de prioriterade förslagen som redovisas i denna rapport dominerar olika aktiviteter för att knyta samman olika aktörer och grupper inom regionen och på så sätt göra mer av mindre. Många av förslagen visar regionala aktörers förväntningar på universitetens roll i den regionala utvecklingen och markerar ett intresse av tätare samverkan meduniversiteten. Förslagen berör alla verksamheter inom universiteten, såväl utbildning, forskning och förvaltning. Bland de prioriterade förslagen finns:• Stimulera gröna affärs och teknikutvecklingsallianser för regionens småföretag• Stimulera ”den lille forskaren” – en modell för småföretagens forskarkollektiv• Utred grönare näringsliv som gemensamt profilområde för regionens universitet• Stärk företagsnyttig forskning & utvecklingsinsatser kring ”age management”• Etablera ett ”integrationsnätverk” för universitetens studenter & det regionalasamhället• Utveckla dialogen mellan universiteten & avnämargrupper i utvecklingen avutbildningar • Skapa regionalt utvecklingslab för bättre samverkan mellan universiteten ochomgivande samhälleInom DARE-projektet kommer nu det material som utvecklats inom framsynsprocessen att användas för utveckling av samverkan inom universiteten, mellan universiteten och med andra intressenter av den regionala utvecklingen, inte minst då de som deltagit i framsynen.
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| 7. |
- Axelsson, Susanna, et al.
(författare)
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Economic aspects of the detection of occlusal dentine caries.
- 2009
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Ingår i: Acta odontologica Scandinavica. - : Informa UK Limited. - 1502-3850 .- 0001-6357. ; 67:1, s. 38-43
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the cost of true-positive occlusal dentine caries detection in permanent molars assessed by: (I) visual-tactile examination, (II) visual-tactile examination combined with bitewing radiographs, and (III) selective radiographic examination of patients with lesions detected clinically. A second aim was to analyse the different strategies when the costs of the subsequent restorative care are considered. METHODS: A model analysis was applied owing to the lack of original articles. Sensitivity and specificity were calculated from a systematic review and included in vitro and in vivo studies of medium and high quality. The direct costs for examinations and restorative care were extracted from the costs of the Public Dental Service in Sweden (2006). RESULTS: The diagnostic costs per true-positive finding were dependent on the occurrence of occlusal caries and increased with decreasing prevalence. The strategy by which radiographs were exposed selectively on the basis of findings from visual-tactile examination resulted in higher initial costs compared with the first and second strategies. When the costs of the subsequent restorative care were added, the selective strategy was most beneficial by up to 26% savings per true-positive diagnosis. However, with this selective strategy, more cases of true-positive dentine caries were assumed would remain undetected as compared with the combined strategy with visual-tactile examination and radiographs for all. CONCLUSIONS: The cost for a true-positive caries diagnosis was inversely related to caries occurrence, and different diagnostic strategies may display contrasting outcomes when subsequent restorative care is taken into account.
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| 8. |
- Baladi, Tom, 1991, et al.
(författare)
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Stealth Fluorescence Labeling for Live Microscopy Imaging of mRNA Delivery
- 2021
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 143:14, s. 5413-5424
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Tidskriftsartikel (refereegranskat)abstract
- Methods for tracking RNA inside living cells without perturbing their natural interactions and functions are critical within biology and, in particular, to facilitate studies of therapeutic RNA delivery. We present a stealth labeling approach that can efficiently, and with high fidelity, generate RNA transcripts, through enzymatic incorporation of the triphosphate of tCO, a fluorescent tricyclic cytosine analogue. We demonstrate this by incorporation of tCO in up to 100% of the natural cytosine positions of a 1.2 kb mRNA encoding for the histone H2B fused to GFP (H2B:GFP). Spectroscopic characterization of this mRNA shows that the incorporation rate of tCO is similar to cytosine, which allows for efficient labeling and controlled tuning of labeling ratios for different applications. Using live cell confocal microscopy and flow cytometry, we show that the tCO-labeled mRNA is efficiently translated into H2B:GFP inside human cells. Hence, we not only develop the use of fluorescent base analogue labeling of nucleic acids in live-cell microscopy but also, importantly, show that the resulting transcript is translated into the correct protein. Moreover, the spectral properties of our transcripts and their translation product allow for their straightforward, simultaneous visualization in live cells. Finally, we find that chemically transfected tCO-labeled RNA, unlike a state-of-the-art fluorescently labeled RNA, gives rise to expression of a similar amount of protein as its natural counterpart, hence representing a methodology for studying natural, unperturbed processing of mRNA used in RNA therapeutics and in vaccines, like the ones developed against SARS-CoV-2.
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| 9. |
- Becquart, Cécile, et al.
(författare)
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Intracellular Absolute Quantification of Oligonucleotide Therapeutics by NanoSIMS
- 2022
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 94:29, s. 10549-10556
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Tidskriftsartikel (refereegranskat)abstract
- Antisense oligonucleotide (ASO)-based therapeutics hold great potential for the treatment of a variety of diseases. Therefore, a better understanding of cellular delivery, uptake, and trafficking mechanisms of ASOs is highly important for early-stage drug discovery. In particular, understanding the biodistribution and quantifying the abundance of ASOs at the subcellular level are needed to fully characterize their activity. Here, we used a combination of electron microscopy and NanoSIMS to assess the subcellular concentrations of a 34S-labeled GalNAc-ASO and a naked ASO in the organelles of primary human hepatocytes. We first cross-validated the method by including a 127I-labeled ASO, finding that the absolute concentration of the lysosomal ASO using two independent labeling strategies gave matching results, demonstrating the strength of our approach. This work also describes the preparation of external standards for absolute quantification by NanoSIMS. For both the 34S and 127I approaches used for our quantification methodology, we established the limit of detection (5 and 2 μM, respectively) and the lower limit of quantification (14 and 5 μM, respectively).
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| 10. |
- Bjerg, Anders, 1982, et al.
(författare)
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Higher Risk of Wheeze in Female than Male Smokers. Results from the Swedish GA(2)LEN Study
- 2013
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Women who smoke have higher risk of lung function impairment, COPD and lung cancer than smoking men. An influence of sex hormones has been demonstrated, but the mechanisms are unclear and the associations often subject to confounding. This was a study of wheeze in relation to smoking and sex with adjustment for important confounders. Methods In 2008 the Global Allergy and Asthma European Network (GA2LEN) questionnaire was mailed to 45.000 Swedes (age 16–75 years), and 26.851 (60%) participated. “Any wheeze”: any wheeze during the last 12 months. “Asthmatic wheeze”: wheeze with breathlessness apart from colds. Results Any wheeze and asthmatic wheeze was reported by 17.3% and 7.1% of women, vs. 15.8% and 6.1% of men (both p<0.001). Although smoking prevalence was similar in both sexes, men had greater cumulative exposure, 16.2 pack-years vs. 12.8 in women (p<0.001). Most other exposures and characteristics associated with wheeze were significantly overrepresented in men. Adjusted for these potential confounders and pack-years, current smoking was a stronger risk factor for any wheeze in women aged <53 years, adjusted odds ratio (aOR) 1.85 (1.56–2.19) vs. 1.60 (1.30–1.96) in men. Cumulative smoke exposure and current smoking each interacted significantly with female sex, aOR 1.02 per pack-year (p<0.01) and aOR 1.28 (p = 0.04) respectively. Female compared to male current smokers also had greater risk of asthmatic wheeze, aOR 1.53 vs. 1.03, interaction aOR 1.52 (p = 0.02). These interactions were not seen in age ≥53 years. Discussion In addition to the increased risk of COPD and lung cancer female, compared to male, smokers are at greater risk of significant wheezing symptoms in younger age. This became clearer after adjustment for important confounders including cumulative smoke exposure. Estrogen has previously been shown to increase the bioactivation of several compounds in tobacco smoke, which may enhance smoke-induced airway inflammation in fertile women.
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| 11. |
- Bjerg, Anders, et al.
(författare)
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Increased Prevalence of Symptoms of Rhinitis but Not of Asthma between 1990 and 2008 in Swedish Adults : Comparisons of the ECRHS and GA(2)LEN Surveys
- 2011
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:2, s. e16082-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The increase in asthma prevalence until 1990 has been well described. Thereafter, time trends are poorly known, due to the low number of high quality studies. The preferred method for studying time trends in prevalence is repeated surveys of similar populations. This study aimed to compare the prevalence of asthma symptoms and their major determinants, rhinitis and smoking, in Swedish young adults in 1990 and 2008. Methods: In 1990 the European Community Respiratory Health Survey (ECRHS) studied respiratory symptoms, asthma, rhinitis and smoking in a population-based sample (86% participation) in Sweden. In 2008 the same symptom questions were included in the Global Allergy and Asthma European Network (GA(2)LEN) survey (60% participation). Smoking questions were however differently worded. The regions (Gothenburg, Uppsala, Umea) and age interval (20-44 years) surveyed both in 1990 (n = 8,982) and 2008 (n = 9,156) were analysed. Results: The prevalence of any wheeze last 12 months decreased from 20% to 16% (p<0.001), and the prevalence of "asthma-related symptoms" was unchanged at 7%. However, either having asthma attacks or using asthma medications increased from 6% to 8% (p<0.001), and their major risk factor, rhinitis, increased from 22% to 31%. Past and present smoking decreased. Conclusion: From 1990 to 2008 the prevalence of obstructive airway symptoms common in asthma did not increase in Swedish young adults. This supports the few available international findings suggesting the previous upward trend in asthma has recently reached a plateau. The fact that wheeze did not increase despite the significant increment in rhinitis, may at least in part be due to the decrease in smoking.
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| 12. |
- Bjerg, Anders, 1982, et al.
(författare)
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The association between asthma and rhinitis is stable over time despite diverging trends in prevalence
- 2015
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 109:3, s. 312-319
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite the well-known association between asthma and rhinitis, in Swedish adults the prevalence of rhinitis rose from 22% to 31% between 1990 and 2008 while asthma prevalence was unchanged. We tested whether the association of rhinitis with asthma was stable over time using the same population-based databases. Methods: Two surveys of adults (20-44 years) living in three regions of Sweden, carried out in 1990 (n = 8982) and 2008 (n = 9156) were compared. Identical questions regarding respiratory symptoms, asthma and rhinitis were used. Asthmatic wheeze: Wheeze with breathlessness apart from colds. Current asthma: Asthma attacks and/or asthma medication use. Results: Subjects with rhinitis had level time trends in asthmatic wheeze, current asthma and most nocturnal respiratory symptoms between 1990 and 2008, adjusted for age, sex, area and smoking. Any wheeze however decreased slightly. In never-smokers asthma symptoms were similarly associated with rhinitis in 1990 and 2008: any wheeze OR 4.0 vs. 4.4 (p = 0.339); asthmatic wheeze OR 6.0 vs. 5.9 (p = 0.937); and current asthma OR 9.6 vs. 7.7 (p = 0.213). In the whole population there were decreases in the asthma symptoms most closely associated to smoking, which decreased by half 1990-2008. Conversely current asthma, which was strongly associated with rhinitis and not with smoking, increased (p < 0.001). Conclusions: The association of rhinitis with asthma was stable between 1990 and 2008. The pattern in the time trends of asthma outcomes strongly suggests that decreased smoking counterbalanced the driving effect of increased rhinitis on asthma prevalence. The findings illustrate the public health benefits of decreased smoking. (c) 2015 Elsevier Ltd. All rights reserved.
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| 13. |
- Blomgren, Johan, et al.
(författare)
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Få indikationer för antibiotikaprofylax
- 2009
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Ingår i: Tandläkartidningen. - : Sveriges Tandläkarförbund. - 0039-6982. ; 101:14, s. 50-54
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Tidskriftsartikel (refereegranskat)abstract
- Tandläkarnas förskrivning av antibiotika har ökat under senare år. Strama (Samverkan mot antibiotikaresistens) redovisar situationer där antibiotikaprofylax kan göra nytta och tillfällen då det inte har någon bevisad effekt.
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| 14. |
- Boianelli, Alessandro, et al.
(författare)
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Cross-Species Translation of Biophase Half-Life and Potency of GalNAc-Conjugated siRNAs
- 2022
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Ingår i: Nucleic Acid Therapeutics. - : Mary Ann Liebert. - 2159-3337 .- 2159-3345. ; 32:6, s. 507-512
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Tidskriftsartikel (refereegranskat)abstract
- Small interfering RNAs (siRNAs) with N-acetylgalactosamine (GalNAc) conjugation for improved liver uptake represent an emerging class of drugs to treat liver diseases. Understanding how pharmacokinetics and pharmacodynamics translate is pivotal for in vivo study design and human dose prediction. However, the literature is sparse on translational data for this modality, and pharmacokinetics in the liver is seldom measured. To overcome these difficulties, we collected time-course biomarker data for 11 GalNAc-siRNAs in various species and applied the kinetic-pharmacodynamic modeling approach to estimate the biophase (liver) half-life and the potency. Our analysis indicates that the biophase half-life is 0.6-3 weeks in mouse, 1-8 weeks in monkey, and 1.5-14 weeks in human. For individual siRNAs, the biophase half-life is 1-8 times longer in human than in mouse, and generally 1-3 times longer in human than in monkey. The analysis indicates that the siRNAs are more potent in human than in mouse and monkey.
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| 15. |
- Bood, Mattias, et al.
(författare)
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Pentacyclic adenine: a versatile and exceptionally bright fluorescent DNA base analogue
- 2018
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Ingår i: Chemical Science. - : Royal Society of Chemistry (RSC). - 2041-6520 .- 2041-6539. ; 9:14, s. 3494-3502
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Tidskriftsartikel (refereegranskat)abstract
- Emissive base analogs are powerful tools for probing nucleic acids at the molecular level. Herein we describe the development and thorough characterization of pentacyclic adenine (pA), a versatile base analog with exceptional fluorescence properties. When incorporated into DNA, pA pairs selectively with thymine without perturbing the B-form structure and is among the brightest nucleobase analogs reported so far. Together with the recently established base analog acceptor qAnitro, pA allows accurate distance and orientation determination via Forster resonance energy transfer (FRET) measurements. The high brightness at emission wavelengths above 400 nm also makes it suitable for fluorescence microscopy, as demonstrated by imaging of single liposomal constructs coated with cholesterolanchored pA-dsDNA, using total internal reflection fluorescence microscopy. Finally, pA is also highly promising for two-photon excitation at 780 nm, with a brightness (5.3 GM) that is unprecedented for a base analog.
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| 16. |
- Bost, Jeremy P., et al.
(författare)
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Novel endosomolytic compounds enable highly potent delivery of antisense oligonucleotides
- 2022
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- The therapeutic and research potentials of oligonucleotides (ONs) have been hampered in part by their inability to effectively escape endosomal compartments to reach their cytosolic and nuclear targets. Splice-switching ONs (SSOs) can be used with endosomolytic small molecule compounds to increase functional delivery. So far, development of these compounds has been hindered by a lack of high-resolution methods that can correlate SSO trafficking with SSO activity. Here we present in-depth characterization of two novel endosomolytic compounds by using a combination of microscopic and functional assays with high spatiotemporal resolution. This system allows the visualization of SSO trafficking, evaluation of endosomal membrane rupture, and quantitates SSO functional activity on a protein level in the presence of endosomolytic compounds. We confirm that the leakage of SSO into the cytosol occurs in parallel with the physical engorgement of LAMP1-positive late endosomes and lysosomes. We conclude that the new compounds interfere with SSO trafficking to the LAMP1-positive endosomal compartments while inducing endosomal membrane rupture and concurrent ON escape into the cytosol. The efficacy of these compounds advocates their use as novel, potent, and quick-acting transfection reagents for antisense ONs.
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| 17. |
- Chávez de Paz, Luis, 1974, et al.
(författare)
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Gram-positive rods prevailing in teeth with apical periodontitis undergoing root canal treatment.
- 2004
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Ingår i: International endodontic journal. - : Wiley. - 0143-2885 .- 1365-2591. ; 37:9, s. 579-87
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To identify Gram-positive rods from root canals of teeth with apical periodontitis and to examine their associations with other species. METHODOLOGY: Consecutive root canal samples (RCSs) from 139 teeth undergoing root canal treatment were analyzed prospectively for cultivable microbes. Gram-positive rods in the first RCS submitted after chemo-mechanical preparation were categorised to genus level by selective media and gas-liquid chromatography (GLC), and identified to species level by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Associations between organisms were measured by odds ratios (OR). RESULTS: In the first samples submitted a total of 158 Gram-positive rods, 115 Gram-positive cocci, 26 Gram-negative rods and 9 Gram-negative cocci, were identified. At genus levels Gram-positive rods were classified into: Lactobacillus spp. (38%), Olsenella spp. (18%), Propionibacterium spp. (13%), Actinomyces spp. (12%), Bifidobacterium spp. (13%) and Eubacterium spp. (6%). The most frequent species were Olsenella uli, Lactobacillus paracasei and Propionibacterium propionicum. In subsequent samples taken during treatment, Gram-positive rods were also identified, although the number of strains was considerably reduced. Positive associations were observed between members of the genus lactobacilli and Gram-positive cocci (OR>2). CONCLUSIONS: Olsenella uli and Lactobacillus spp. predominated over other Gram-positive rods. A possible association exists between Lactobacillus spp. and Gram-positive cocci in root canals of teeth with apical periodontitis receiving treatment.
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| 18. |
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| 19. |
- Dahlén, Anna, et al.
(författare)
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Clustering of deletions on chromosome 13 in benign and low-malignant lipomatous tumors
- 2003
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 103:5, s. 616-623
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Tidskriftsartikel (refereegranskat)abstract
- Deletions and structural rearrangements of the long arm of chromosome 13 are frequently observed in benign and low-malignant lipomatous tumors, but nothing is known about their molecular genetic consequences. We assessed the karyotypes of 40 new and 22 previously published cases (35 ordinary lipomas, 15 spindle cell/pleomorphic lipomas, 2 myxolipomas, 1 angiomyxolipoma and 9 atypical lipomatous tumors) with chromosome 13-abnormalities, and found bands 13q12-22 to be frequently affected. Twenty-seven cases with structural abnormalities within this region were selected for breakpoint and deletion mapping by metaphase fluorescence in situ hybridization (FISH), using a set of 20 probes. Deletions were found in 23 of 27 cases. The remaining 4 cases had seemingly balanced rearrangements. The breakpoints were scattered but clustered to band 13q14, and in all cases with unbalanced abnormalities, a limited region within band 13q14 was partially or completely deleted. A deletion within band 13q14 was found together with a breakpoint on the other homologue in 5 cases, 4 of which could be tested further with regard to the status of the retinoblastoma (RB1)-gene. In all 4 cases, only 1 copy of the gene was deleted. In addition to the breaks and deletions in the vicinity of the RB1-locus, several other regions of 13q were recurrently affected, e.g., in the vicinity of the hereditary breast cancer (BRCA2; 13q12)- and lipoma HMGIC fusion partner (LHFP; 13q13)- genes. Our findings strongly indicate that deletion of a limited region (approximately 2.5 Mbp) within 13q14, distal to the RB1-locus, is of importance in the development of a subset of lipomatous tumors.
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| 20. |
- Dahlén, Anders, 1977, et al.
(författare)
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Estimating the limiting reducing power of SmI2/H2O/amine and YbI2/H2O/amine by efficient reduction of unsaturated hydrocarbons.
- 2006
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Ingår i: The Journal of organic chemistry. - : American Chemical Society (ACS). - 0022-3263 .- 1520-6904. ; 71:4, s. 1576-80
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Tidskriftsartikel (refereegranskat)abstract
- The mixture of samarium diiodide, amine, and water (SmI2/H2O/Et3N) is known to be a particularly powerful reductant, but until now the limiting reducing power has not been determined. A series of unsaturated hydrocarbons with varying half-wave reduction potentials (E(1/2) = -1.6 to -3.4 V, vs SCE) have been treated with SmI2/H2O/Et3N and YbI2/H2O/Et3N, respectively. All hydrocarbons with potentials of -2.8 V or more positive were readily reduced with SmI2/H2O/Et3N, whereas all hydrocarbons with potentials of -2.3 V or more positive were readily reduced using YbI2/H2O/Et3N. This defines limiting values of the chemical reducing power of SmI2/H2O/Et3N to -2.8 V and of YbI2/H2O/Et3N to -2.3 V vs SCE.
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| 21. |
- Dahlén, Anders, 1977, et al.
(författare)
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Exploring SmBr2-, SmI2-, and YbI2-mediated reactions assisted by microwave irradiation.
- 2005
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Ingår i: Chemistry (Weinheim an der Bergstrasse, Germany). - : Wiley. - 0947-6539. ; 11:11, s. 3279-84
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Tidskriftsartikel (refereegranskat)abstract
- The use of microwave heating in lanthanide(II) halide (LnX2 = SmBr2, SmI2, and YbI2) mediated reduction and coupling reactions has been investigated for a variety of functional groups including alpha,beta-unsaturated esters, aldehydes, ketones, imines, and alkyl halides. Good to quantitative transformations were obtained within a few minutes without the addition of any co-solvents, such as hexamethyl phosphoramide (HMPA). The redox potential of YbI2 in tetrahydrofuran (THF) has been determined as -1.02+/-0.05 V (versus Ag/AgNO3) by cyclic voltammetry. A large selectivity difference in various reactions was observed depending on the redox potential of the LnX2 reagent. The more powerful reductant, SmBr2, afforded mainly pinacol-coupling products of ketones whereas the weaker reductant YbI2 afforded mainly reduction products. The results indicate that the reducing power of LnX2 has a large impact on not only the pinacol coupling/reduction product ratio of ketones but also on other substrates in which there are competing coupling and reduction reactions. The use of in situ generated LnX2 has also been explored and proven useful in many of these reactions.
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| 22. |
- Dahlén, Anna, et al.
(författare)
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Fusion, disruption, and expression of HMGA2 in bone and soft tissue chondromas
- 2003
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Ingår i: Modern Pathology. - 1530-0285. ; 16:11, s. 1132-1140
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Tidskriftsartikel (refereegranskat)abstract
- Soft tissue and skeletal chondromas are rare entities, and only 21 cases with abnormal karyotypes have been reported. A survey of these, and 10 new cases reported herein, showed that the 12q13-15 segment is nonrandomly involved in structural rearrangements in chondromas. The HMGA2 (HMGI-C) locus in 12q15 is frequently rearranged in other benign mesenchymal tumors, and this study aimed at characterizing the expression of HMGA2 in chondromatous tumors. The material consisted of 8 soft tissue and 6 skeletal chondromas, as well as of 14 skeletal chondrosarcomas. All cases had been cytogenetically analyzed. Expression of HMGA2 could be assessed by RT-PCR in 8 chondromas and 13 chondrosarcomas. HMGA2 was expressed in 4 of six soft tissue chondromas, all displaying 12q-rearrangements at cytogenetic analysis. A truncated transcript (exons 1-3), but not a full-length (exons 1-5) transcript, was detected in three of them, suggesting activation through an intragenic rearrangement. One soft tissue chondroma had a t(3;12)(q27;q15), and the RT-PCR analysis revealed an HMGA2-LPP fusion transcript, composed of HMGA2 exons 1-3 and LPP exons 9-11. An identical fusion transcript previously has been identified in lipoma and pulmonary chondroid hamartoma. In the fourth soft tissue chondroma, a full-length transcript was detected, indicating expression of at least one intact allele. Both skeletal chondromas expressed HMGA2. In one of them, a full-length transcript was detected, even though 12q was cytogenetically unaffected. A truncated or full-length transcript was found in 8 of 13 chondrosarcomas, 4 of which displayed 12q rearrangements. Possibly, cryptic rearrangements were present among the many complex marker chromosomes in the remaining 4 cases.
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| 23. |
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| 24. |
- Dahlén, Anders, 1977, et al.
(författare)
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Mechanistic study of the SmI2/H2O/amine-mediated reduction of alkyl halides: amine base strength (pKBH+) dependent rate.
- 2005
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 127:23, s. 8340-7
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Tidskriftsartikel (refereegranskat)abstract
- The kinetics of the SmI(2)/H(2)O/amine-mediated reduction of 1-chlorodecane has been studied in detail. The rate of reaction is first order in amine and 1-chlorodecane, second order in SmI(2), and zero order in H(2)O. Initial rate studies of more than 20 different amines show a correlation between the base strength (pK(BH+) of the amine and the logarithm of the observed initial rate, in agreement with Bronsted catalysis rate law. To obtain the activation parameters, the rate constant for the reduction was determined at different temperatures (0 to +40 degrees C, DeltaH++ = 32.4 +/- 0.8 kJ mol(-1), DeltaS++ = -148 +/- 1 J K(-1) mol(-1), and DeltaG++(298K) = 76.4 +/- 1.2 kJ mol(-1)). Additionally, the (13)C kinetic isotope effects (KIE) were determined for the reduction of 1-iododecane and 1-bromodecane. Primary (13)C KIEs (k(12)/k(13), 20 degrees C) of 1.037 +/- 0.007 and 1.062 +/- 0.015, respectively, were determined for these reductions. This shows that cleavage of the carbon-halide bond occurs in the rate-determining step. A mechanism of the SmI(2)/H(2)O/amine-mediated reduction of alkyl halides is proposed on the basis of these results.
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| 25. |
- Dahlén, Anders, 1977, et al.
(författare)
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Microwave-assisted generation of lanthanide(II) halides in THF and simple quantitative determination
- 2004
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Ingår i: European Journal of Inorganic Chemistry. - : Wiley. - 1434-1948 .- 1099-0682. ; :15, s. 3020-3024
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Tidskriftsartikel (refereegranskat)abstract
- Lanthanide(II) reagents (SMI2, SmBr2, YbI2, EuI2) have been prepared rapidly in high yields using microwave-assisted heating. Samarium diiodide is obtained as a saturated solution in THF (0.13 m) within 5 min and ytterbium diiodide (0.065 m) after 45 min. A simple method for quantitative determination of LnX(2) in THF is also described by utilizing the instantaneous reaction with ketones in the presence of an amine and water. This method establishes the concentration of the active single - electron-donor species, i.e. Ln(2+). ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004).
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| 26. |
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| 27. |
- Dahlén, Anders, 1977, et al.
(författare)
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Samarium(II) iodide mediated reductions - Influence of various additives
- 2004
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Ingår i: European Journal of Inorganic Chemistry. - : Wiley. - 1434-1948 .- 1099-0682. ; :17, s. 3393-3403
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Tidskriftsartikel (refereegranskat)abstract
- Samarium(II) iodide is a one-electron transfer reagent that has become highly appreciated as a mild and selective reducing agent in recent years. It has been found experimentally that various additives and co-solvents largely control the reactivity of SmI2. This microreview provides an overview of the current knowledge of the reagent SmI2 as a reducing agent, in particular with additives that increase its reactivity. The use of various proton sources is covered, as well as the effect of co-solvents. Furthermore, the very powerful reagent mixture SmI2/H2O/amine is also described. (C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
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| 28. |
- Dahlén, Anders, et al.
(författare)
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The relation of the CCA subspace method to a balanced reduction of an autoregressive model
- 2004
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Ingår i: Journal of Econometrics. - 0304-4076 .- 1872-6895. ; 118:1-2, s. 293-312
-
Tidskriftsartikel (refereegranskat)abstract
- In this paper we consider an identification procedure, called MEST, for multivariate time series based on AR-modeling and stochastically balanced truncation and compare it with the CCA subspace method. The stochastically balancing of multivariate AR-models is described using just linear algebraic operations, i.e., no algebraic Riccati equations need to be solved. Both identification procedures are formulated in a uniform manner, and from these expressions we conclude that the only difference is that MEST uses a covariance extension, whereas CCA is based on the sample covariances only. Finally, it is shown that MEST and CCA are asymptotically equivalent.
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| 29. |
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| 30. |
- Dahlén, Gunnar, 1944, et al.
(författare)
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Necrobacillosis in humans.
- 2011
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Ingår i: Expert review of anti-infective therapy. - : Informa UK Limited. - 1744-8336 .- 1478-7210. ; 9:2, s. 227-36
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Tidskriftsartikel (refereegranskat)abstract
- Necrobacillosis, often used synonymously with Lemierre's syndrome, is a form of abscess infection in the peritonsillar area associated with a thrombophlebitis and caused by the strict anaerobic species Fusobacterium necrophorum. The thrombosis formed affects the internal jugular vein, from which the bacteria are seeded out in the bloodstream and cause bacteremia. Septicemia is a common complication with an often fatal outcome. Necrobacillosis is very rare and is referred to as the 'forgotten disease'. It is probably frequently overlooked in clinical practice in its early and milder forms such as tonsillitis (sore throat) and peritonsillar abscess. F. necrophorum frequently participates in these infections and is thus suspected to have an etiological role in Lemierre's syndrome. Similarly, F. necrophorum seems to play an important role in noma (cancrum oris) and this disease is also included in the necrobacillosis complex. Diagnosis of infections of the necrobacillosis complex seeks to disclose F. necrophorum in swab samples or blood culture. The most commonly used therapy is metronidazole in combination with penicillin or amoxicillin. Clindamycin is also an option, especially in cases of penicillin allergy.
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| 31. |
- Dahlén, Gunnar, 1944, et al.
(författare)
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Subgingival bacteria in Ghanaian adolescents with or without progression of attachment loss
- 2014
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Ingår i: Journal of Oral Microbiology. - : Informa UK Limited. - 2000-2297. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study describes subgingival bacterial profiles associated with clinical periodontal status in Ghanaian adolescents with or without progression of attachment loss. Materials and methods: Among 500 adolescents included in a cohort study, 397 returned 2 years later for a periodontal re-examination, including full-mouth CAL measurements. At follow-up, a subgroup of 98 adolescents was also subjected to bacterial sampling with paper points at four periodontal sites (mesial aspect of 11, 26, 31, and 46) and analyzed with the checkerboard DNA - DNA hybridization technique against DNA-probes from nine periodontitis-associated bacterial species. Results: The 98 Ghanaian adolescents examined in the present study were similar to the entire group examined at the 2-year follow-up with respect to age, gender, and CAL > 3 mm. A high detection frequency of Fusobacterium nucleatum and Prevotella intermedia (> 99%) using checkerboard analysis was found, while for Aggregatibacter actinomycetemcomitans the detection frequency was < 50%. A strong correlation was found at the individual level between the presence of P. intermedia and the total CAL change, and P. intermedia and Porphyromonas gingivalis were strongly correlated with a change in CAL and probing pocket depth (PPD) at the sampled sites. In a linear regression model, a significant discriminating factor for the total CAL change in the dentition during the 2-year follow-up period was obtained for P. intermedia and public school. Conclusion: This study indicates that subgingival bacterial species other than A. actinomycetemcomitans, for example, P. intermedia, have a significant association with periodontal breakdown (change in CAL) in Ghanaian adolescents with progression of periodontal attachment loss.
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| 32. |
- Dahlén, Lisa, et al.
(författare)
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Comparison of different collection systems for sorted household waste in Sweden
- 2007
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Ingår i: Waste Management. - : Elsevier BV. - 0956-053X .- 1879-2456. ; 27:10, s. 1298-1305
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Tidskriftsartikel (refereegranskat)abstract
- Composition and quantity per person of municipal solid waste (MSW) have been analyzed in six municipalities in southern Sweden with similar socio-economic conditions but with different collection systems. Samples of residual waste have been sorted, classified and weighed in 21 categories during 26 analyses that took place from 1998-2004. Collection data of the total waste flow, including source sorted recycling materials, in the same area have been compiled and compared. Multivariate data analyses have been applied. Weight-based billing reduced delivered amounts of residual household waste by 50%, but it is unknown to what extent improper material paths had developed. With curbside collection more metal, plastic and paper packaging was separated and left to recycling. When separate collection of biodegradables was included in the curbside system, the overall sorting of dry recyclables increased. The large uncertainty associated with waste composition analyses makes it difficult to draw strong conclusions regarding the effects on specific recyclables or the changes in the composition of the residual waste.
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| 33. |
- Dahlén, Lisa, et al.
(författare)
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Comparison of total waste flow from households in 35 Swedish municipalities
- 2007
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Ingår i: SARDINIA 2007. - Cagliari : CISA, Environmental Sanitary Engineering Centre. - 9788862650038
-
Konferensbidrag (refereegranskat)abstract
- The objective of the study was to identify the total waste flow from households in a number of municipalities (cities) in Sweden, make comparisons and discuss methods as well as obstacles to benchmarking. Overall aim is decision support for local authorities in waste management planning. Average amount of household waste per citizen vary widely within Sweden. There is no obvious explanation to the inconsistent amounts. Weight based collection fees has caused a considerable decrease of collected waste amounts in some Swedish municipalities, but no clear effect in others. In general the amounts per capita of separated recyclables, as well as unseparated waste in bins and bags, have levelled out the last few years. In contrast the diverse wastes delivered by the public to supervised Recycling Centers show a trend of increase. 16 sources of error in collection data have been identified and described.
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| 34. |
- Dahlén, Lisa, et al.
(författare)
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Evaluation of recycling programmes in household waste collection systems
- 2010
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Ingår i: Waste Management & Research. - 0734-242X .- 1096-3669. ; 28:7, s. 577-586
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Tidskriftsartikel (refereegranskat)abstract
- A case study and a literature review have been carried out to address the two questions: how can waste flow data from collection systems be interpreted and compared? and which factors are decisive in the results of recycling programmes in household waste collection systems? The aim is to contribute to the understanding of how recycling programmes affect the quantity of waste and sorting activities. It is shown how the results from various waste sorting systems can be interpreted and made comparable. A set of waste flow indicators is proposed, which together with generic system descriptions can facilitate comparisons of different collections systems. The evaluation of collection systems depends on the system boundaries and will always be site-specific to some degree. Various factors are relevant, e.g. environmental objectives, technical function, operating costs, types of recyclable materials collected separately, property-close collection or drop-off systems, economic incentives, information strategies, residential structure, social codes, etc. Kerbside collection of recyclables and weight-based billing led to increased waste sorting activities in the case study. Forty-three decisive factors are listed and discussed.
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| 35. |
- Dahlén, Lisa, et al.
(författare)
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Inconsistent pathways of household waste
- 2009
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Ingår i: Waste Management. - : Elsevier BV. - 0956-053X .- 1879-2456. ; 29:6, s. 1798-1806
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to provide policy-makers and waste management planners with information about how recycling programs affect the quantities of specific materials recycled and disposed of. Two questions were addressed: which factors influence household waste generation and pathways? and how reliable are official waste data? Household waste flows were studied in 35 Swedish municipalities, and a wide variation in the amount of waste per capita was observed. When evaluating the effect of different waste collection policies, it was found to be important to identify site-specific factors influencing waste generation. Eleven municipal variables were investigated in an attempt to explain the variation. The amount of household waste per resident was higher in populous municipalities and when net commuting was positive. Property-close collection of dry recyclables led to increased delivery of sorted metal, plastic and paper packaging. No difference was seen in the amount of separated recyclables per capita when weight-based billing for the collection of residual waste was applied, but the amount of residual waste was lower. Sixteen sources of error in official waste statistics were identified and the results of the study emphasize the importance of reliable waste generation and composition data to underpin waste management policies.
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| 36. |
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| 37. |
- Dahlén, Lisa, et al.
(författare)
-
Manual för plockanalys av hushållsavfall i kärl och säckar
- 2005
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Rapporten är resultatet av ett samarbete mellan NSR och Luleå Tekniska Universitet. Här föreslås en metod för plockanalys av hushållsavfall avsedd för svenska förhållanden. Den bygger på egna praktiska erfarenheter och litteraturstudier. Stor vikt har lagts vid vilken arbetsinsats som är praktiskt och ekonomiskt rimlig i förhållande till resultatets precision. Första delen av rapporten beskriver bakgrunden och diskuterar varje steg i en plockanalys med referenser till tidigare genomförda analyser i Sverige och utomlands. Kostnader och behov av utrustning och personal diskuteras. Rapportens andra del är skriven som en manual, som steg för steg ger instruktioner för genomförande av plockanalys. Här ingår även skyddsåtgärder med hänsyn till risker i arbetsmiljön. Det finns också detaljerade sorteringsinstruktioner, en mall för sorteringsprotokoll samt en mall för utvärdering av resultaten.
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| 38. |
- Dahlén, Lisa, et al.
(författare)
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Methods for household waste composition studies
- 2008
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Ingår i: Waste Management. - : Elsevier BV. - 0956-053X .- 1879-2456. ; 28:7, s. 1100-1112
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Tidskriftsartikel (refereegranskat)abstract
- The question is how to conduct household waste composition studies. The review is divided into three parts: overview of known methods, sampling theory, and the waste components. Twenty methods are listed and commented on. There is no adopted, working international standard. In accordance with Pierre Gy’s Theory of Sampling, the seven types of sampling errors, when collecting and splitting solid samples, are described and commented on in relation to sampling of household solid waste. It is concluded that the most crucial choices in household waste composition studies are: to divide the investigation into relevant number and types of strata; to decide the required sample size and number of samples; to choose the sampling location, i.e., sampling at household level or sampling from loads of waste collection vehicles; and to choose the type and number of waste component categories to be investigated. Various classifications of household waste components used in composition studies are listed and discussed. Difficulties and weaknesses of the reviewed methods are discussed and concluded in suggested questions for further research.
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| 39. |
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| 40. |
- Dahlén, Lisa, et al.
(författare)
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Pay as you throw : strengths and weaknesses of weight-based billing in household waste collection systems in Sweden
- 2010
-
Ingår i: Waste Management. - : Elsevier BV. - 0956-053X .- 1879-2456. ; 30:1, s. 23-31
-
Tidskriftsartikel (refereegranskat)abstract
- Householders' response to weight-based billing for the collection of household waste was investigated with the aim of providing decision support for waste management policies. Three questions were addressed: How much and what kind of information on weight-based billing is discernible in generic Swedish waste collection statistics? Why do local authorities implement weight-based billing, and how do they perceive the results? and, Which strengths and weaknesses of weight-based billing have been observed on the local level? The study showed that municipalities with pay-by-weight schemes collected 20% less household waste per capita than other municipalities. Surprisingly, no part of this difference could be explained by higher recycling rates. Nevertheless, the majority of waste management professionals were convinced that recycling had increased as a result of the billing system. A number of contradicting strengths and weaknesses of weight-based billing were revealed.
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| 41. |
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| 42. |
- Dahlén, Lisa, et al.
(författare)
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Trends in municipal solid waste composition
- 2004
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Ingår i: The 3rd Intercontinental Landfill Research Symposium November 29th - December 2nd, 2004 in Toya, Hokkaido Japan. - Hokkaido : Center for Applied Ethics and Philosophy, Hokkaido University. ; , s. 157-
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 43. |
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| 44. |
- Dahlén, Torsten, et al.
(författare)
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Adverse outcomes in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors : Follow-up of patients diagnosed 2002-2017 in a complete coverage and nationwide agnostic register study
- 2022
-
Ingår i: American Journal of Hematology. - : Wiley. - 0361-8609 .- 1096-8652. ; 97:4, s. 421-430
-
Tidskriftsartikel (refereegranskat)abstract
- Tyrosine kinase inhibitors (TKIs) have profoundly improved the clinical outcome for patients with chronic myeloid leukemia (CML), but their overall survival is still subnormal and the treatment is associated with adverse events. In a large cohort-study, we assessed the morbidity in 1328 Swedish CML chronic phase patients diagnosed 2002-2017 and treated with TKIs, as compared to that in carefully matched control individuals. Several Swedish patient registers with near-complete nationwide coverage were utilized for data acquisition. Median follow-up was 6 (IQR, 3-10) years with a total follow-up of 8510 person-years for the full cohort. Among 670 analyzed disease categories, the patient cohort showed a significantly increased risk in 142 while, strikingly, no category was more common in controls. Increased incidence rate ratios/IRR (95% CI) for more severe events among patients included acute myocardial infarction (AMI) 2.0 (1.5-2.6), heart failure 2.6 (2.2-3.2), pneumonia 2.8 (2.3-3.5), and unspecified sepsis 3.5 (2.6-4.7). When comparing patients on 2nd generation TKIs vs. imatinib in a within-cohort analysis, nilotinib generated elevated IRRs for AMI (2.9; 1.5-5.6) and chronic ischemic heart disease (2.2; 1.2-3.9), dasatinib for pleural effusion (11.6; 7.6-17.7) and infectious complications, for example, acute upper respiratory infections (3.0; 1.4-6.0). Our extensive real-world data reveal significant risk increases of severe morbidity in TKI-treated CML patients, as compared to matched controls, particularly for 2nd generation TKIs. Whether this increased morbidity may also translate into increased mortality, thus preventing CML patients to achieve a normalized overall survival, needs to be further explored.
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| 45. |
- Dahlen, Torsten, et al.
(författare)
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Cardiovascular Events Associated With Use of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia : A Population-Based Cohort Study
- 2016
-
Ingår i: Annals of Internal Medicine. - Karolinska Univ Hosp, Stockholm, Sweden. Karolinska Inst, Stockholm, Sweden. Reg Canc Ctr, Uppsala, Sweden. Univ Uppsala Hosp, Uppsala, Sweden. Umea Univ, Umea, Sweden. Skane Univ Hosp, Lund, Sweden. [Dahlen, Torsten; Bjorkholm, Magnus; Ohm, Lotta; Stenke, Leif] Karolinska Univ Hosp Solna, Div matol, Dept Med, SE-17176 Stockholm, Sweden. [Edgren, Gustaf; Lambe, Mats] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, eden. [Hoglund, Martin; Olsson-Stromberg, Ulla] Univ Hosp, Dept Med Sci, SE-75185 Uppsala, Sweden. [Hoglund, Martin; Olsson-Stromberg, Ulla] Univ Hosp, Div Hematol, SE-75185 Uppsala, Sweden. [Sandin, Fredrik] Uppsala Univ Hosp, Reg Canc Ctr, SE-75185 Uppsala, Sweden. [Sjalander, Anders] Umea Univ, Dept Publ Hlth & Clin Med, SE-90185 Umea, Sweden. [Richter, Johan] Skane Univ Hosp, Dept Hematol & Vasc Disorders, SE-22241 Lund, Sweden. [Back, Magnus] Karolinska Univ Hosp, Dept Cardiol, SE-17176 Stockholm, Sweden.. - 0003-4819 .- 1539-3704. ; 165:3, s. 161-166
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Tyrosine kinase inhibitors (TKIs) have increased survival dramatically for patients with chronic myeloid leukemia (CML), but continuous administration of these drugs may elicit long-term toxicity.Objective: To investigate the incidence of vascular events in patients with CML treated with first-and second-generation TKIs.Design: Retrospective cohort study using nationwide population-based registries.Setting: Sweden.Patients: All patients diagnosed with chronic-phase CML in Sweden from 2002 to 2012 and treated with a TKI, and 5 age- and sex-matched control individuals per patient.Measurements: Relative risks, expressed as incidence rate ratios comparing patients with control individuals, were calculated. Events per 1000 person-years were assessed in interdrug comparisons.Results: 896 patients, 94.4% with documented TKI treatment, were followed for a median of 4.2 years. There were 54 arterial and 20 venous events in the CML cohort, corresponding to relative risks of 1.5 (95% CI, 1.1 to 2.1) and 2.0 (CI, 1.2 to 3.3), respectively. The event rate for myocardial infarction was higher in patients treated with nilotinib or dasatinib (29 and 19 per 1000 person-years, respectively) than in those receiving imatinib (8 per 1000 person-years), although data are limited and the CIs were wide and overlapped. Among 31 patients treated with a TKI who had myocardial infarction, 26 (84%) had at least 1 major cardiac risk factor diagnosed before the event occurred.Limitations: Patients may have been exposed to multiple TKIs. Data on second-and third-generation TKIs were limited.Conclusion: An increased risk for arterial and venous vascular events was seen in patients with CML treated with a TKI. Further study is needed to determine whether the risk for myocardial infarction increases with second-generation drugs.
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| 46. |
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| 47. |
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| 48. |
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| 49. |
- Ek, A., et al.
(författare)
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Chronic rhinosinusitis in asthma is a negative predictor of quality of life: results from the Swedish GA(2)LEN survey
- 2013
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Ingår i: Allergy. - : Wiley. - 0105-4538 .- 1398-9995. ; 68:10, s. 1314-1321
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAsthma and chronic rhinosinusitis (CRS) both impair quality of life, but the quality-of-life impact of comorbid asthma and CRS is poorly known. The aim of this study was to evaluate the impact of CRS and other relevant factors on quality of life in asthmatic subjects. MethodsThis Swedish cohort (age 17-76years) consists of 605 well-characterized asthmatics with and without CRS, 110 individuals with CRS only, and 226 controls and is part of the Global Allergy and Asthma European Network (GA(2)LEN) survey. The Mini Asthma Quality of Life Questionnaire (mAQLQ), the Euro Quality of Life (EQ-5D) health questionnaire, spirometry, skin prick test (SPT), exhaled nitric oxide (FeNO), smell test, and peak nasal inspiratory flow were used. ResultsSubjects having both asthma and CRS have lower mAQLQ scores in all domains (P<0.001) and a lower EQ-5D index value and EQ-5D VAS value (P<0.001) compared to those with asthma only. Asthmatics with CRS have significantly lower FEV1%pred and FVC%pred (88.4 [85.1-91.7] and 99.9 [96.7-103.0], respectively) compared with asthma only (91.9 [90.3-93.4] and 104.0 [102.5-105.5], respectively P<0.05). Multiple regression analysis shows that low asthma quality of life is associated with having CRS (P<0.0001), lower lung function (P=0.008), current smoking (P=0.01), BMI>30kg/m(2) (P=0.04), high age (P=0.03), and a negative SPT (P=0.04). ConclusionsComorbid CRS was a significant and independent negative predictor of quality of life in asthmatics. Other negative factors were lower lung function, current smoking, obesity, advanced age, and having nonatopic asthma.
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| 50. |
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