| 1. |
- Looi Chee Leong, Jeffrey, et al.
(författare)
-
Caudate nucleus volumes in frontotemporal lobar degeneration : differential atrophy in subtypes
- 2008
-
Ingår i: American Journal of Neuroradiology. - 0195-6108 .- 1936-959X. ; 29:8, s. 1537-1543
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Frontostriatal circuits involving the caudate nucleus have been implicated in frontotemporal lobar degeneration (FTLD). We assessed caudate nucleus volumetrics in FTLD and subtypes: frontotemporal dementia (FTD, n = 12), semantic dementia (SD, n = 13), and progressive nonfluent aphasia (PNFA, n = 9) in comparison with healthy controls (n = 27) and subjects with Alzheimer disease (AD, n = 19). MATERIALS AND METHODS: Diagnoses were based on accepted clinical criteria. Manual volume measurement of the head and body of the caudate, excluding the tail, was conducted on T1-weighted brain MR imaging scans, using a published protocol, by a single analyst blinded to the diagnosis. RESULTS: Paired t tests (P < .05) showed that the right caudate nucleus volume was significantly larger than the left in controls and PNFA. No hemispheric asymmetry was found in AD, ETD, and SD. Across the groups, there was a positive partial correlation between the left caudate nucleus volume and Mini-Mental State Examination (MMSE) scores (r = 0.393, n = 76, P = .001) with higher left caudate volumes associated with higher MMSE scores. Multivariate analysis of covariance was used to assess the statistical significance between the subject groups (AD, ETD, SD, PNFA, and controls) as independent variables and raw right/left caudate volumes at the within-subject level (covariates: age and intracranial volume; P < .05). Control volume was largest, followed by AD (93% of control volume), SD (92%), PNFA (79%), and ETD (75%). CONCLUSIONS: Volume of the head and body of the caudate nucleus differs in subtypes of FTLD, due to differential frontostriatal dysfunction in subtypes being reflected in structural change in the caudate, and is correlated with cognition
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Karlsson, Beatrice, et al.
(författare)
-
Quasispecies dynamics and molecular evolution of human norovirus capsid P region during chronic infection
- 2009
-
Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 90:2, s. 432-441
-
Tidskriftsartikel (refereegranskat)abstract
- In this novel study, we have for the first time identified evolutionarily conserved capsid residues in an individual chronically infected with norovirus (GGII.3). From 2000 to 2003, a total of 147 P1-1 and P2 capsid sequences were sequenced and investigated for evolutionarily conserved and functionally important residues by the evolutionary trace (ET) algorithm. The ET algorithm revealed more absolutely conserved residues (ACR) in the P1-1 domain (47/53, 88 %) as compared with the P2 domain (86/133, 64 %). The capsid P1-1 and P2 domains evolved in time-dependent manner, with a distinct break point observed between autumn/winter of year 2000 (isolates P1, P3 and P5) and spring to autumn of year 2001 (isolates P11, P13 and P15), which presumably coincided with a change of clinical symptoms. Furthermore, the ET analysis revealed a similar receptor-binding pattern as reported for Norwalk and VA387 strains, with the CS-4 and CS-5 patch (Norwalk strain) including residues 329 and 377 and residues 306 and 310, respectively, all being ACR in all partitions. Most interesting was that residues 343, 344, 345, 374, 390 and 391 of the proposed receptor A and B trisaccharide binding site (VA387 strain) within the P2 domain remained ACR in all partitions, presumably because there was no selective advantage to alter the histo blood group antigens (HBGA) receptor binding specificity. In conclusion, this study provides novel insights to the evolutionary process of norovirus during chronic infection.
|
|
| 5. |
- Mukonzo, Jackson K, et al.
(författare)
-
A novel polymorphism in ABCB1 gene, CYP2B6*6 and sex predict single-dose efavirenz population pharmacokinetics in Ugandans.
- 2009
-
Ingår i: British journal of clinical pharmacology. - : Wiley. - 1365-2125 .- 0306-5251. ; 68:5, s. 690-9
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS: Efavirenz exhibits pharmacokinetic variability causing varied clinical response. The aim was to develop an integrated population pharmacokinetic/pharmacogenetic model and investigate the impact of genetic variations, sex, demographic and biochemical variables on single-dose efavirenz pharmacokinetics among Ugandan subjects, using NONMEM. METHODS: Efavirenz plasma concentrations (n = 402) from 121 healthy subjects were quantified by high-performance liquid chromatography. Subjects were genotyped for 30 single nucleotide polymorphisms (SNPs), of which six were novel SNPs in CYP2B6, CYP3A5 and ABCB1. The efavirenz pharmacokinetics was described by a two-compartment model with zero- followed by first-order absorption. RESULTS: Apparent oral clearance (95% confidence interval) was 4 l h l(-1) (3.5, 4.5) in extensive metabolizers. In the final model, incorporating multiple covariates, statistical significance was found only for CYP2B6*6 and CYP2B6*11 on apparent oral clearance as well as ABCB1 (rs3842) on the relative bioavailability. Subjects homozygous for CYP2B6*6 (G516T, A785G) and *11 displayed 21 and 20% lower apparent oral clearance, respectively. Efavirenz relative bioavailability was 26% higher in subjects homozygous for ABCB1 (rs3842). The apparent peripheral volume of distribution was twofold higher in women compared with men. CONCLUSIONS: The model identified the four factors CYP2B6*6, CYP2B6*11, a novel variant allele in ABCB1 (rs3842) and sex as major predictors of efavirenz plasma exposure in a healthy Ugandan population after single-dose administration. Use of mixed-effects modelling allowed the analysis and integration of multiple pharmacogenetic and demographic covariates in a pharmacokinetic population model.
|
|
| 6. |
- Strom, Oskar, et al.
(författare)
-
Long-term cost and effect on quality of life of osteoporosis-related fractures in Sweden
- 2008
-
Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674. ; 79:2, s. 269-280
-
Tidskriftsartikel (refereegranskat)abstract
- Background and purpose Few economic or quality-of-life studies have investigated the long-term consequences of fragility fractures. This prospective observational data collection study assessed the cost and quality of life related to hip, vertebral, and wrist fracture 13-18 months after the fracture, based on 684 patients surviving 18 months after fracture. Patients and methods Data regarding resource use and quality of life related to fractures was collected using questionnaires at 7 research centers in Sweden. Information was collected using patient records, register sources, and by asking the patient. Quality of life was estimated using the EQ-5D questionnaire. Direct and indirect costs were estimated from a societal standpoint. Results The mean fracture-related cost 13-18 months after a hip, vertebral, or wrist fracture were estimated to be (sic)2,422, (sic)3,628, and (sic)316, respectively. Between 12 and 18 months after hip, vertebral, and wrist fracture, utility increased by 0.03, 0.05, and 0.02, respectively. Compared to prefracture levels, the mean loss in quality of life between 13 and 18 months after fracture was estimated to be 0.05, 0.11, and 0.005 for hip, vertebral, and wrist fracture. Interpretation The sample of vertebral fracture patients was fairly small and included a high proportion of fractures leading to hospitalization, but the results indicate higher long-term costs and greater loss in quality of life related to vertebral fracture than previously believed.
|
|
