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- Edenbrandt, Lars, et al.
(författare)
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Area of ischemia assessed by physicians and software packages from myocardial perfusion scintigrams
- 2014
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Ingår i: BMC Medical Imaging. - : BioMed Central. - 1471-2342 .- 1471-2342. ; 14:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: The European Society of Cardiology recommends that patients with greater than 10% area of ischemia should receive revascularization. We investigated inter-observer variability for the extent of ischemic defects reported by different physicians and by different software tools, and if inter-observer variability was reduced when the physicians were provided with a computerized suggestion of the defects. Methods: Twenty-five myocardial perfusion single photon emission computed tomography (SPECT) patients who were regarded as ischemic according to the final report were included. Eleven physicians in nuclear medicine delineated the extent of the ischemic defects. After at least two weeks, they delineated the defects again, and were this time provided a suggestion of the defect delineation by EXINI Heart(TM) (EXINI). Summed difference scores and ischemic extent values were obtained from four software programs. Results: The median extent values obtained from the 11 physicians varied between 8% and 34%, and between 9% and 16% for the software programs. For all 25 patients, mean extent obtained from EXINI was 17.0% (+/- standard deviation (SD) 14.6%). Mean extent for physicians was 22.6% (+/- 15.6%) for the first delineation and 19.1% (+/- 14.9%) for the evaluation where they were provided computerized suggestion. Intra-class correlation (ICC) increased from 0.56 (95% confidence interval (CI) 0.41-0.72) to 0.81 (95% CI 0.71-0.90) between the first and the second delineation, and SD between physicians were 7.8 (first) and 5.9 (second delineation). Conclusions: There was large variability in the estimated ischemic defect size obtained both from different physicians and from different software packages. When the physicians were provided with a suggested delineation, the inter-observer variability decreased significantly.
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| 2. |
- Evangelou, Evangelos, et al.
(författare)
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Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22
- 2011
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:2, s. 349-355
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Osteoarthritis (OA) is the most prevalent form of arthritis and accounts for substantial morbidity and disability, particularly in older people. It is characterised by changes in joint structure, including degeneration of the articular cartilage, and its aetiology is multifactorial with a strong postulated genetic component. Methods A meta-analysis was performed of four genome-wide association (GWA) studies of 2371 cases of knee OA and 35 909 controls in Caucasian populations. Replication of the top hits was attempted with data from 10 additional replication datasets. Results With a cumulative sample size of 6709 cases and 44 439 controls, one genome-wide significant locus was identified on chromosome 7q22 for knee OA (rs4730250, p = 9.2 x 10(-9)), thereby confirming its role as a susceptibility locus for OA. Conclusion The associated signal is located within a large (500 kb) linkage disequilibrium block that contains six genes: PRKAR2B (protein kinase, cAMP-dependent, regulatory, type II, beta), HPB1 (HMG-box transcription factor 1), COG5 (component of oligomeric golgi complex 5), GPR22 (G protein-coupled receptor 22), DUS4L (dihydrouridine synthase 4-like) and BCAP29 (B cell receptor-associated protein 29). Gene expression analyses of the (six) genes in primary cells derived from different joint tissues confirmed expression of all the genes in the joint environment.
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| 3. |
- Nakajima, Yoko, et al.
(författare)
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Clinical, biochemical and molecular analysis of 13 Japanese patients with beta-ureidopropionase deficiency demonstrates high prevalence of the c.977G > A (p.R326Q) mutation
- 2014
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Ingår i: Journal of Inherited Metabolic Disease. - : Wiley. - 0141-8955 .- 1573-2665. ; 37:5, s. 801-812
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Tidskriftsartikel (refereegranskat)abstract
- beta-ureidopropionase (beta UP) deficiency is an autosomal recessive disease characterized by N-carbamyl-beta-amino aciduria. To date, only 16 genetically confirmed patients with beta UP deficiency have been reported. Here, we report on the clinical, biochemical and molecular findings of 13 Japanese beta UP deficient patients. In this group of patients, three novel missense mutations (p.G31S, p.E271K, and p.I286T) and a recently described mutation (p.R326Q) were identified. The p.R326Q mutation was detected in all 13 patients with eight patients being homozygous for this mutation. Screening for the p.R326Q mutation in 110 Japanese individuals showed an allele frequency of 0.9 %. Transient expression of mutant beta UP enzymes in HEK293 cells showed that the p.E271K and p.R326Q mutations cause profound decreases in activity (a parts per thousand currency sign 1.3 %). Conversely, beta UP enzymes containing the p.G31S and p.I286T mutations possess residual activities of 50 and 70 %, respectively, suggesting we cannot exclude the presence of additional mutations in the non-coding region of the UPB1 gene. Analysis of a human beta UP homology model revealed that the effects of the mutations (p.G31S, p.E271K, and p.R326Q) on enzyme activity are most likely linked to improper oligomer assembly. Highly variable phenotypes ranging from neurological involvement (including convulsions and autism) to asymptomatic, were observed in diagnosed patients. High prevalence of p.R326Q in the normal Japanese population indicates that beta UP deficiency is not as rare as generally considered and screening for beta UP deficiency should be included in diagnosis of patients with unexplained neurological abnormalities.
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