| 868371. |
- Svensson, Maria A., et al.
(författare)
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Testing mutual exclusivity of ETS rearranged prostate cancer
- 2011
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Ingår i: Laboratory Investigation. - : Elsevier BV. - 0023-6837 .- 1530-0307. ; 91:3, s. 404-412
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a clinically heterogeneous and multifocal disease. More than 80% of patients with prostate cancer harbor multiple geographically discrete cancer foci at the time of diagnosis. Emerging data suggest that these foci are molecularly distinct consistent with the hypothesis that they arise as independent clones. One of the strongest arguments is the heterogeneity observed in the status of E26 transformation specific (ETS) rearrangements between discrete tumor foci. The clonal evolution of individual prostate cancer foci based on recent studies demonstrates intertumoral heterogeneity with intratumoral homogeneity. The issue of multifocality and interfocal heterogeneity is important and has not been fully elucidated due to lack of the systematic evaluation of ETS rearrangements in multiple tumor sites. The current study investigates the frequency of multiple gene rearrangements within the same focus and between different cancer foci. Fluorescence in situ hybridization (FISH) assays were designed to detect the four most common recurrent ETS gene rearrangements. In a cohort of 88 men with localized prostate cancer, we found ERG, ETV1, and ETV5 rearrangements in 51% (44/86), 6% (5/85), and 1% (1/86), respectively. None of the cases demonstrated ETV4 rearrangements. Mutual exclusiveness of ETS rearrangements was observed in the majority of cases; however, in six cases, we discovered multiple ETS or 50 fusion partner rearrangements within the same tumor focus. In conclusion, we provide further evidence for prostate cancer tumor heterogeneity with the identification of multiple concurrent gene rearrangements. Laboratory Investigation (2011) 91, 404-412; doi: 10.1038/labinvest.2010.179; published online 25 October 2010
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| 868372. |
- Svensson, Majlis, et al.
(författare)
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Acute pyelonephritis and renal scarring are caused by dysfunctional innate immunity in mCxcr2 heterozygous mice.
- 2011
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Ingår i: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 80:10, s. 1064-1072
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Tidskriftsartikel (refereegranskat)abstract
- The CXCR1 receptor and chemokine CXCL8 (IL-8) support neutrophil-dependent clearance of uropathogenic Escherichia coli from the urinary tract. CXCR1 is reduced in children prone to pyelonephritis, and heterozygous hCXCR1 polymorphisms are more common in this patient group than in healthy individuals, strongly suggesting a disease association. Since murine CXCR2 (mCXCR2) is functionally similar to human CXCR1, we determined effects of gene heterozygosity on the susceptibility to urinary tract infection by infecting heterozygous (mCxcr2(+/-)) mice with uropathogenic Escherichia coli. Clearance of infection and tissue damage were assessed as a function of innate immunity in comparison to that in knockout (mCxcr2(-/-)) and wild-type (mCxcr2(+/+)) mice. Acute sepsis-associated mortality was increased and bacterial clearance drastically impaired in heterozygous compared to wild-type mice. Chemokine and neutrophil responses were delayed along with evidence of neutrophil retention and unresolved kidney inflammation 1 month after infection. This was accompanied by epithelial proliferation and subepithelial fibrosis. The heterozygous phenotype was intermediate, between knockout and wild-type mice, but specific immune cell infiltrates that accompany chronic infection in knockout mice were not found. Hence, the known heterozygous CXCR1 polymorphisms may predispose patients to acute pyelonephritis and urosepsis.
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| 868373. |
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| 868374. |
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| 868375. |
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| 868376. |
- Svensson, Malin, et al.
(författare)
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Adherence to CPAP therapy in Down syndrome: the population-based DISCOVERY study
- 2023
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Ingår i: JOURNAL OF CLINICAL SLEEP MEDICINE. - : American Academy of Sleep Medicine (AASM). - 1550-9389 .- 1550-9397. ; 19:3, s. 453-458
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Tidskriftsartikel (refereegranskat)abstract
- Study Objectives: Persons with Down syndrome (DS) have an increased risk of obstructive sleep apnea (OSA) needing continuous positive airway pressure (CPAP), but data on the therapy and outcomes in this population are scarce. We aimed to compare patient characteristics and outcomes of CPAP treatment for patients with OSA with and without DS. Methods: This was a population-based, longitudinal study on patients initiating CPAP therapy between July 2010 and March 2018 in Sweden and a population-based sex-and age-matched control group (control:case ratio 5:1), with linked data from the Swedish National Patient Registry and the Prescribed Drug Registry (DISCOVERY study cohort). Results: Patients with DS (n = 64) had a higher apnea-hypopnea index (51.7 & PLUSMN; 30.3 vs 36.8 & PLUSMN; 29.1 events/h, P < .001), Epworth Sleepiness Scale score (13.7 & PLUSMN; 5.9 vs 11.0 & PLUSMN; 4.9, P = .001), rate of previous surgery of tonsils and/or adenoids (21.9% vs 8.2%, P = .001), and more thyroid replacement hormone therapy (45.3% vs 7.8%, P < .001), but lower use of cardiovascular drugs (7.8% vs 22.3%, P = .003) compared with controls. At follow-up after 1.3 & PLUSMN; 0.9 years, there were no differences in nocturnal CPAP usage time (5.6 & PLUSMN; 2.4 vs 5.5 & PLUSMN; 2.0 hours, P = .77), CPAP adherence & GE; 4 hours/night (62% vs 65%, P = .93), or improvement in Epworth Sleepiness Scale score (-5.4 & PLUSMN; 6.8 vs-5.0 & PLUSMN; 2.0, P = .84) between DS and non-DS patients. Conclusions: OSA severity was substantially higher in patients with DS despite an increased rate of tonsil surgery. Treatment outcomes in terms of adherence and improved daytime sleepiness were comparable between groups, underlining the importance of both OSA diagnosis and treatment in patients with DS.
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| 868377. |
- Svensson, Mikael, 1980, et al.
(författare)
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Adolescent alcohol and illicit drug use among first- and second-generation immigrants in Sweden.
- 2010
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Ingår i: Scandinavian journal of public health. - London : SAGE Publications. - 1651-1905 .- 1403-4948. ; 38:2, s. 184-91
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Tidskriftsartikel (refereegranskat)abstract
- This article compares adolescent alcohol and illicit drug use among first- and second-generation immigrants from Nordic, non-Nordic European and non-European countries with that of the native Swedish majority population.
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| 868378. |
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| 868379. |
- Svensson, Mikael, 1980-, et al.
(författare)
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Adolescents alcohol-use and economic conditions : a multilevel analysis of data from a period with big economic changes
- 2010
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Ingår i: European Journal of Health Economics. - New York, USA : Springer. - 1618-7598 .- 1618-7601. ; 11:6, s. 533-541
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Tidskriftsartikel (refereegranskat)abstract
- This paper examines how the unemployment rate is related to adolescent alcohol use and experience of binge drinking during a time period characterized by big societal changes. The paper uses repeated cross-sectional adolescent survey data from a Swedish region, collected in 1988, 1991, 1995, 1998, 2002 and 2005, and merges this with data on local unemployment rates for the same time periods. Individual level frequency of alcohol use as well as experience of binge drinking is connected to local level unemployment rate to estimate the relationship using multilevel modeling. The model includes municipality effects controlling for time-invariant differences between municipalities as well as year fixed effects controlling for municipality-invariant changes over time in alcohol use. The results show that the unemployment rate is negatively associated with adolescents' alcohol use and the experience of binge drinking. When the unemployment rate increases, more adolescents do not drink at all. Regular drinking (twice per month or more) is, on the other hand, unrelated to the unemployment rate. Examining gender-differences in the relationship, it is shown that the results are driven by behavior in girls, whereas drinking among boys does not show any significant relationship with changes in the unemployment rate.
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| 868380. |
- Svensson, Maria, et al.
(författare)
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Age at onset of childhood-onset type 1 diabetes and the development of end-stage renal disease: a nationwide population-based study.
- 2006
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Ingår i: Diabetes Care. ; 29:3, s. 538-42
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To analyze the impact of age at onset on the development of end-stage renal disease (ESRD) due to diabetic nephropathy in a nationwide population-based cohort with childhood-onset type 1 diabetes. RESEARCH DESIGN AND METHODS: A record linkage between two nationwide registers, the Swedish Childhood Diabetes Registry, including 12,032 cases with childhood-onset diabetes, and the Swedish Registry for Active Treatment of Uraemia was performed. Log-rank test was used to test differences between cumulative risk curves of developing ESRD due to diabetic nephropathy in three different strata of age at onset (0-4, 5-9, and 10-14 years). RESULTS: At a maximum follow-up of 27 years, 33 patients had developed ESRD due to diabetic nephropathy and all had a diabetes duration >15 years. In total, 4,414 patients had diabetes duration >15 years, and thus the risk in this cohort to develop ESRD was 33 of 4,414 (0.7%). A significant difference in risk of developing ESRD was found between the youngest (0-4 years) and the two older (5-9 and 10-14 years) age-at-onset strata (P = 0.03 and P = 0.001, respectively). A significant difference in the risk of developing ESRD was also found between children with prepubertal (0-4 and 5-9 years, n = 2,424) and pubertal (10-14 years, n = 2000) onset of diabetes (P = 0.002). No patient with onset of diabetes before 5 years of age had developed ESRD. CONCLUSIONS: With a median duration of 21 years in this population-based Swedish cohort with childhood-onset diabetes, <1% of the patients had developed ESRD due to diabetic nephropathy, and a prepubertal onset of diabetes seems to prolong the time to development of ESRD.
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