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Search: WFRF:(Lonnqvist T)

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  • Hakkinen, K, et al. (author)
  • Implementation of CYP2D6 copy-number imputation panel and frequency of key pharmacogenetic variants in Finnish individuals with a psychotic disorder
  • 2022
  • In: The pharmacogenomics journal. - : Springer Science and Business Media LLC. - 1473-1150 .- 1470-269X. ; 22:3, s. 166-172
  • Journal article (peer-reviewed)abstract
    • We demonstrate that CYP2D6 copy-number variation (CNV) can be imputed using existing imputation algorithms. Additionally, we report frequencies of key pharmacogenetic variants in individuals with a psychotic disorder from the genetically bottle-necked population of Finland. We combined GWAS chip and CYP2D6 CNV data from the Breast Cancer Pain Genetics study to construct an imputation panel (n = 902) for CYP2D6 CNV. The resulting data set was used as a CYP2D6 CNV imputation panel in 9262 non-related individuals from the SUPER-Finland study. Based on imputation of 9262 individuals we confirm the higher frequency of CYP2D6 ultrarapid metabolizers and a 22-fold enrichment of the UGT1A1 decreased function variant rs4148323 (UGT1A1*6) in Finland compared with non-Finnish Europeans. Similarly, the NUDT15 variant rs116855232 was highly enriched in Finland. We demonstrate that imputation of CYP2D6 CNV is possible and the methodology enables studying CYP2D6 in large biobanks with genome-wide data.
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  • Virtanen, KA, et al. (author)
  • Differential effects of rosiglitazone and metformin on adipose tissue distribution and glucose uptake in type 2 diabetic subjects
  • 2003
  • In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 52:2, s. 283-290
  • Journal article (peer-reviewed)abstract
    • We evaluated the effects of rosiglitazone (4 mg b.i.d.) and metformin (1 g b.i.d.) monotherapy for 26 weeks on adipose tissue insulin-stimulated glucose uptake in patients (n = 41) with type 2 diabetes. Before and after the treatment, glucose uptake was measured using 2-[18F]fluoro-2-deoxyglucose and positron emission tomography and adipose tissue masses were quantified using magnetic resonance imaging. Rosiglitazone improved insulin-stimulated whole-body glucose uptake by 44% (P < 0.01 vs. placebo). Mean body weight was unchanged in the rosiglitazone group, while it decreased by 2.0 kg in the metformin group (P < 0.05 vs. placebo). In visceral adipose tissue, glucose uptake increased by 29% (from 17.8 ± 2.0 to 23.0 ± 2.6 μmol · kg−1 · min−1, P < 0.05 vs. placebo) in the rosiglitazone group but to a lesser extent (17%) in the metformin group (from 16.2 ± 1.5 to 18.9 ± 1.7 μmol · kg−1 · min−1, P < 0.05 vs. baseline). Because the visceral adipose tissue mass simultaneously decreased with both treatments (P < 0.05), no change was observed in total visceral glucose uptake per depot. Rosiglitazone significantly enhanced glucose uptake in the femoral subcutaneous area, either when expressed per tissue mass (from 10.8 ± 1.2 to 17.1 ± 1.7 μmol · kg−1 · min−1, P < 0.01 vs. placebo) or per whole-fat depot (P < 0.05 vs. placebo). In conclusion, metformin treatment resulted in improvement of glycemic control without enhancement of peripheral insulin sensitivity. The improved insulin sensitivity of the nonabdominal subcutaneous adipose tissue during treatment with rosiglitazone partly explains the enhanced whole-body insulin sensitivity and underlies the central role of adipose tissue for action of peroxisome proliferator-activated receptor γ agonist in vivo.
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  • Hallsten, K, et al. (author)
  • Rosiglitazone but not metformin enhances insulin- and exercise-stimulated skeletal muscle glucose uptake in patients with newly diagnosed type 2 diabetes
  • 2002
  • In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 51:12, s. 3479-3485
  • Journal article (peer-reviewed)abstract
    • Rosiglitazone, a thiazolidinedione, enhances peripheral insulin sensitivity in patients with type 2 diabetes. Because the synergic action of insulin and exercise has been shown to be decreased in insulin resistance, the aim of this study was to compare the effects of rosiglitazone and metformin on muscle insulin responsiveness at rest and during exercise in patients with type 2 diabetes. Therefore, 45 patients with newly diagnosed or diet-treated type 2 diabetes were randomized for treatment with rosiglitazone (4 mg b.i.d.), metformin (1 g b.i.d.), or placebo in a 26-week double-blind trial. Skeletal muscle glucose uptake was measured using fluorine-18-labeled fluoro-deoxy-glucose and positron emission tomography (PET) during euglycemic-hyperinsulinemic clamp and one-legged exercise before and after the treatment period. Rosiglitazone (P < 0.05) and metformin (P < 0.0001) treatment lowered the mean glycosylated hemoglobin. The skeletal muscle glucose uptake was increased by 38% (P < 0.01) and whole-body glucose uptake by 44% in the rosiglitazone group. Furthermore, the exercise-induced increment during insulin stimulation was enhanced by 99% (P < 0.0001). No changes were observed in skeletal muscle or whole-body insulin sensitivity in the metformin group. In conclusion, rosiglitazone but not metformin 1) improves insulin responsiveness in resting skeletal muscle and 2) doubles the insulin-stimulated glucose uptake rate during physical exercise in patients with type 2 diabetes. Our results suggest that rosiglitazone improves synergic action of insulin and exercise.
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  • Bille-Brahe, U, et al. (author)
  • A repetition-prediction study of European parasuicide populations : a summary of the first report from part II of the WHO/EURO Multicentre Study on Parasuicide in co-operation with the EC concerted action on attempted suicide.
  • 1997
  • In: Acta Psychiatrica Scandinavica. - : Wiley. - 0001-690X .- 1600-0447. ; 95:2, s. 81-6
  • Journal article (peer-reviewed)abstract
    • One of the aims of the European Study on Parasuicide, which was initiated by the Regional Office for the European Region of the World Health Organization in the mid-1980s, was to try to identify social and personal characteristics that are predictive of future suicidal behaviour. A follow-up interview study (the Repetition-Prediction Study) was designed, and to date 1145 first-wave interviews have been conducted at nine research centres, representing seven European countries. The present paper provides an abridged version of the first report from the study. The design and the instrument used (The European Parasuicide Study Interview Schedules, EPSIS I and II) are described. Some basic characteristics of the samples from the various centres, such as sex, age, method of suicide attempt, and history of previous attempts, are presented and compared. The male/female sex ratio ranged from 0.41 to 0.85; the mean age range for men was 33-45 years and that for women was 29-45 years. At all of the centres, self-poisoning was the most frequently employed method. On average, more than 50% of all respondents had attempted suicide at least once previously. The representativeness of the samples is discussed. There were differences between the centres in several respects, and also in some cases the representativeness of the different samples varied. Results obtained from analyses based on pooled data should therefore be treated with caution.
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  • Grahn, Petra, et al. (author)
  • Early disc degeneration in radiotherapy-treated childhood brain tumor survivors
  • 2023
  • In: BMC Musculoskeletal Disorders. - : BioMed Central (BMC). - 1471-2474. ; 24:1
  • Journal article (peer-reviewed)abstract
    • BackgroundChildhood brain tumor (BT) survivors have an increased risk of treatment-related late effects, which can reduce health-related quality of life and increase morbidity. This study aimed to investigate lumbar disc degeneration in magnetic resonance imaging (MRI) in adult survivors of radiotherapy-treated childhood BT compared to age and sex-matched population controls.MethodsIn this cross-sectional comparative study, 127 survivors were identified from hospital registries. After a mean follow-up of 20.7 years (range 5-33.1), 67 survivors (mean age 28.4, range 16.2-43.5) were investigated with MRI and compared to 75 sex-matched population-based controls. Evaluated MRI phenotypes included Pfirrmann grading, , intervertebral disc protrusions, extrusions, and high-intensity-zone-lesions (HIZ). Groups were also compared for known risk factors of lumbar intervertebral disc (IVD) degeneration.ResultsChildhood BT survivors had higher Pfirrmann grades than controls at all lumbar levels (all p < 0.001). Lumbar disc protrusions at L4-5 (p = 0.02) and extrusions at L3-4 (p = 0.04), L4-5 (p = 0.004), and L5-S1 (p = 0.01) were significantly more common in the BT group compared to the control. The survivor cohort also had significantly more HIZ-lesons than the controls (n=13 and n=1, p=0.003). Age at diagnosis was associated with lower degree of IVD degeneration (p < 0.01). Blood pressure correlated with IVD degeneration (P < 0.05).ConclusionsSigns of early disc degeneration related to tumor treatment can be seen in the IVDs of survivors. Disc degeneration was more severe in children treated in adolescence.
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  • Lehtonen, J. M., et al. (author)
  • Diagnostic value of serum biomarkersFGF21andGDF15compared to muscle sample in mitochondrial disease
  • 2021
  • In: Journal of Inherited Metabolic Disease. - : Wiley. - 0141-8955 .- 1573-2665. ; 44:2, s. 469-480
  • Journal article (peer-reviewed)abstract
    • The aim of this study was to compare the value of serum biomarkers, fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15), with histological analysis of muscle in the diagnosis of mitochondrial disease. We collected 194 serum samples from patients with a suspected or known mitochondrial disease. Biomarkers were analyzed blinded using enzyme-labeled immunosorbent assay. Clinical data were collected using a structured questionnaire. Only 39% of patients with genetically verified mitochondrial disease had mitochondrial pathology in their muscle histology. In contrast, biomarkers were elevated in 62% of patients with genetically verified mitochondrial disease. Those with both biomarkers elevated had a muscle manifesting disorder and a defect affecting mitochondrial DNA expression. If at least one of the biomarkers was induced and the patient had a myopathic disease, a mitochondrial DNA expression disease was the cause with 94% probability. Among patients with biomarker analysis and muscle biopsy taken <12 months apart, a mitochondrial disorder would have been identified in 70% with analysis of FGF21 and GDF15 compared to 50% of patients whom could have been identified with muscle biopsy alone. Muscle findings were nondiagnostic in 72% (children) and 45% (adults). Induction of FGF21 and GDF15 suggest a mitochondrial etiology as an underlying cause of a muscle manifesting disease. Normal biomarker values do not, however, rule out a mitochondrial disorder, especially if the disease does not manifest in muscle. We suggest that FGF21 and GDF15 together should be first-line diagnostic investigations in mitochondrial disease complementing muscle biopsy.
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  • Lonnqvist, PA, et al. (author)
  • Caudal opioids - Reply
  • 2003
  • In: PAEDIATRIC ANAESTHESIA. - : Wiley. - 1155-5645. ; 13:6, s. 554-554
  • Journal article (other academic/artistic)
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