| 41. |
- Behndig, Annelie, et al.
(författare)
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Airway antioxidant and inflammatory responses to diesel exhaust exposure in healthy humans.
- 2006
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 27:2, s. 359-365
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Tidskriftsartikel (refereegranskat)abstract
- Pulmonary cells exposed to diesel exhaust (DE) particles in vitro respond in a hierarchical fashion with protective antioxidant responses predominating at low doses and inflammation and injury only occurring at higher concentrations. In the present study, the authors examined whether similar responses occurred in vivo, specifically whether antioxidants were upregulated following a low-dose DE challenge and investigated how these responses related to the development of airway inflammation at different levels of the respiratory tract where particle dose varies markedly. A total of 15 volunteers were exposed to DE (100 microg x m(-3) airborne particulate matter with a diameter of <10 microm for 2 h) and air in a double-blinded, randomised fashion. At 18 h post-exposure, bronchoscopy was performed with lavage and mucosal biopsies taken to assess airway redox and inflammatory status. Following DE exposure, the current authors observed an increase in bronchial mucosa neutrophil and mast cell numbers, as well as increased neutrophil numbers, interleukin-8 and myeloperoxidase concentrations in bronchial lavage. No inflammatory responses were seen in the alveolar compartment, but both reduced glutathione and urate concentrations were increased following diesel exposure. In conclusion, the lung inflammatory response to diesel exhaust is compartmentalised, related to differing antioxidant responses in the conducting airway and alveolar regions.
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| 42. |
- Behndig, Annelie F., et al.
(författare)
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Effects of controlled diesel exhaust exposure on apoptosis and proliferation markers in bronchial epithelium : an in vivo bronchoscopy study on asthmatics, rhinitics and healthy subjects
- 2015
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Ingår i: BMC Pulmonary Medicine. - : Springer Science and Business Media LLC. - 1471-2466. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epidemiological evidence demonstrates that exposure to traffic-derived pollution worsens respiratory symptoms in asthmatics, but controlled human exposure studies have failed to provide a mechanism for this effect. Here we investigated whether diesel exhaust (DE) would induce apoptosis or proliferation in the bronchial epithelium in vivo and thus contribute to respiratory symptoms.Methods: Moderate (n = 16) and mild (n = 16) asthmatics, atopic non-asthmatic controls (rhinitics) (n = 13) and healthy controls (n = 21) were exposed to filtered air or DE (100 μg/m 3 ) for 2 h, on two separate occasions. Bronchial biopsies were taken 18 h post-exposure and immunohistochemically analysed for pro-apoptotic and anti-apoptotic proteins (Bad, Bak, p85 PARP, Fas, Bcl-2) and a marker of proliferation (Ki67). Positive staining was assessed within the epithelium using computerized image analysis.Results: No evidence of epithelial apoptosis or proliferation was observed in healthy, allergic or asthmatic airways following DE challenge.Conclusion: In the present study, we investigated whether DE exposure would affect markers of proliferation and apoptosis in the bronchial epithelium of asthmatics, rhinitics and healthy controls, providing a mechanistic basis for the reported increased airway sensitivity in asthmatics to air pollutants. In this first in vivo exposure investigation, we found no evidence of diesel exhaust-induced effects on these processes in the subject groups investigated.
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| 43. |
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| 44. |
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| 45. |
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| 46. |
- Bjerg, Anders, et al.
(författare)
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Time trends in asthma and wheeze in Swedish children 1996-2006 : prevalence and risk factors by sex
- 2010
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 65:1, s. 48-55
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recent data suggest that the previously rising trend in childhood wheezing symptoms has plateaued in some regions. We sought to investigate sex-specific trends in wheeze, asthma, allergic conditions, allergic sensitization and risk factors for wheeze.Methods: We compared two population-based cohorts of 7 to 8-year olds from the same Swedish towns in 1996 and 2006 using parental expanded ISAAC questionnaires. In 1996, 3430 (97%) and in 2006, 2585 (96%) questionnaires were completed. A subset was skin prick tested: in 1996, 2148 (88%) and in 2006, 1700 (90%) children participated.Results: No significant change in the prevalence of current wheeze (P = 0.13), allergic rhinitis (P = 0.18) or eczema (P = 0.22) was found despite an increase in allergic sensitization (20.6-29.9%, P < 0.01). In boys, however, the prevalence of current wheeze (12.9-16.4%, P < 0.01), physician-diagnosed asthma (7.1-9.3%, P = 0.03) and asthma medication use increased. In girls the prevalence of current symptoms and conditions tended to decrease. The prevalence of all studied risk factors for wheeze and asthma increased in boys relative to girls from 1996 to 2006, thus increasing the boy-to-girl prevalence ratio in risk factors.Conclusions: The previously reported increase in current wheezing indices has plateaued in Sweden. Due to increased diagnostic activity, physician diagnoses continue to increase. Time trends in wheezing symptoms differed between boys and girls, and current wheeze increased in boys. This was seemingly explained by the observed increases in the prevalence of risk factors for asthma in boys compared with girls. In contrast to the current symptoms of wheeze, rhinitis or eczema, the prevalence of allergic sensitization increased considerably.
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| 47. |
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| 48. |
- Bjerg Bäcklund, Anders, 1982-
(författare)
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Epidemiology of asthma in primary school children
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Childhood asthma has increased worldwide, although recent studies report a prevalence plateau in some western countries.Aims: To investigate the prevalence of asthma and the associated risk factor patterns from ages 7-8 to 11-12 with special emphasis on the hereditary component, and further to study prevalence trends at age 7-8 from 1996 to 2006 and the possible determinants of these trends.Methods: The studies involved two cohorts from Kiruna, Luleå and Piteå: one previously identified cohort of 3430 children age 7-8 followed by yearly questionnaires until age 11-12 with 97% yearly participation. Skin-prick tests for allergic sensitisation were performed at ages 7-8 and 11-12 in subsets of 2148 and 2155 children respectively (88% of invited). In 2006 a new cohort of 7-8-year-olds was identified and examined identically. 2585 (96% of invited) and 1700 (90% of invited) participated in the questionnaire and skin-prick tests, respectively. The questionnaire included questions about symptoms of asthma, allergic rhinitis and eczema, and possible risk factors.Results: In the 1996 cohort, from age 7-8 to 11-12 the prevalence of physician-diagnosed asthma increased (5.7%-7.7%, P<0.01) while current wheeze decreased (11.7%-9.4%, P<0.01), and 34.7% reported ever wheee at ≥one occasion. Remission was 10% of which half relapsed during the study. Remission was significantly lower among sensitised children. The strongest risk factors for current asthma at ages 7-8 and 11-12 were allergic sensitisation (OR 5) and family history of asthma (OR 3). Several other significant risk factors, e.g. respiratory infections, damp house and low birth weight, had lost importance at age 11-12. At age 7-8, parental asthma was a stronger risk factor (OR 3-4) than parental rhinitis or eczema (OR 1.5-2). Sibling asthma had no independent effect. Biparental asthma had a multiplicative effect (OR 10). Maternal and paternal asthma was equally important, regardless of the child’s sex and sensitisation status.From 1996 to 2006 the prevalence of current wheeze and asthma at age 7-8 did not increase (P=0.13, P=0.18), while lifetime prevalence of ever wheeze and physician-diagnosed asthma increased (P<0.01, P=0.01). Symptoms of rhinitis and eczema were unchanged, despite 45% increase (P<0.01) in allergic sensitisation. For current asthma the adjusted population attributable fractions of sensitisation and parental asthma increased (35%-41%, 27%-45%). This was however balanced by decreased exposure to infections, maternal smoking and home dampness, resulting in stable asthma prevalence. Stratification by sex revealed that current wheeze increased in boys (P<0.01) but tended to decrease in girls (P=0.37), seemingly due to symptom persistence in males. Several asthma indices followed this pattern. The boy-to-girl ratio in exposure to all studied risk factors increased, which may explain the sex-specific prevalence trends in wheeze.Conclusions: The prevalence of current asthma and wheeze did not increase statistically significantly. However, the risk factor pattern has changed considerably since 1996, which will presumably affect the clinical features of childhood wheeze in this region. Sex-specific trends in wheeze can be explained by changes in exposure, and trends in risk factors should be explored parallel to prevalence trends.
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| 49. |
- Björkblom, Benny, et al.
(författare)
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Distinct metabolic hallmarks of WHO classified adult glioma subtypes
- 2022
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Ingår i: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 24:9, s. 1454-1468
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Gliomas are complex tumors with several genetic aberrations and diverse metabolic programs contributing to their aggressive phenotypes and poor prognoses. This study defines key metabolic features that can be used to differentiate between glioma subtypes, with potential for improved diagnostics and subtype targeted therapy.METHODS: Cross-platform global metabolomic profiling coupled with clinical, genetic, and pathological analysis of glioma tissue from 224 tumors - oligodendroglioma (n=31), astrocytoma (n=31) and glioblastoma (n=162) - were performed. Identified metabolic phenotypes were evaluated in accordance with the WHO classification, IDH-mutation, 1p/19q-codeletion, WHO-grading 2-4, and MGMT promoter methylation.RESULTS: Distinct metabolic phenotypes separate all six analyzed glioma subtypes. IDH-mutated subtypes, expressing 2-hydroxyglutaric acid, were clearly distinguished from IDH-wildtype subtypes. Considerable metabolic heterogeneity outside of the mutated IDH pathway were also evident, with key metabolites being high expression of glycerophosphates, inositols, monosaccharides and sugar alcohols and low levels of sphingosine and lysoglycerophospholipids in IDH-mutants. Among the IDH-mutated subtypes, we observed high levels of amino acids, especially glycine and 2-aminoadipic acid, in grade 4 glioma, and N-acetyl aspartic acid in low-grade astrocytoma and oligodendroglioma. Both IDH-wildtype and mutated oligodendroglioma and glioblastoma were characterized by high levels of acylcarnitines, likely driven by rapid cell growth and hypoxic features. We found elevated levels of 5-HIAA in gliosarcoma and a subtype of oligodendroglioma not yet defined as a specific entity, indicating a previously not described role for the serotonin pathway linked to glioma with bimorphic tissue.CONCLUSION: Key metabolic differences exist across adult glioma subtypes.
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| 50. |
- Björnsson, Bergthor, et al.
(författare)
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Associating Liver Partition and Portal Vein Ligation for Primary Hepatobiliary Malignancies and Non-Colorectal Liver Metastases
- 2016
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Ingår i: Scandinavian Journal of Surgery. - : SAGE PUBLICATIONS LTD. - 1457-4969 .- 1799-7267. ; 105:3, s. 158-162
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Associating liver partition and portal vein ligation for staged hepatectomy may increase the possibility of radical resection in the case of liver malignancy. Concerns have been raised about the high morbidity and mortality associated with the procedure, particularly when applied for diagnoses other than colorectal liver metastases. The aim of this study was to analyze the initial experience with associating liver partition and portal vein ligation for staged hepatectomy in cases of non-colorectal liver metastases and primary hepatobiliary malignancies in Scandinavia. Materials and Methods: A retrospective analysis of all associating liver partition and portal vein ligation for staged hepatectomy procedures performed at two Swedish university hospitals for non-colorectal liver metastases and primary hepatobiliary malignancies was performed. The primary focus was on the safety of the procedure. Results and Conclusion: Ten patients were included: four had hepatocellular cancer, three had intrahepatic cholangiocarcinoma, one had a Klatskin tumor, one had ocular melanoma metastasis, and one had a metastasis from a Wilms tumor. All patients completed both operations, and the highest grade of complication (according to the Clavien-Dindo classification) was 3A, which was observed in one patient. No 90-day mortality was observed. Radical resection (R0) was achieved in nine patients, while the resection was R2 in one patient. The low morbidity and mortality observed in this cohort compared with those of earlier reports on associating liver partition and portal vein ligation for staged hepatectomy for diagnoses other than colorectal liver metastases may be related to the selection of patients with limited comorbidity. In addition, procedures other than associating liver partition and portal vein ligation for staged hepatectomy had been avoided in most of the patients. In conclusion, associating liver partition and portal vein ligation for staged hepatectomy can be applied to primary hepatobiliary malignancies and non-colorectal liver metastases with acceptable rates of morbidity and mortality.
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