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Biomedical subjects

J Wikström

Publications and source records attributed to J Wikström.

At least 19 recordsLinked to original sources
PubMed2002

Chromosome 19q13 and multiple sclerosis susceptibility in Finland: a linkage and two-stage association study.

Several studies have previously provided some albeit weak evidence for linkage or association between chromosome 19q13 and multiple sclerosis (MS) susceptibility. We performed a two-stage association analysis with 19 markers spanning 7 Mb/5.5 cM of 19q13. In stage 1 analysis (135 MS families) allelic and haplotypic associations were found with markers within or close to the ApoE-ApoC subregion. These observations were taken as a hypothesis, which was tested in stage 2 in 125 families. However, none of the initial associations were replicated suggesting that they were most likely due to chance. Linkage analysis was performed in 27 Finnish multiplex families using 10 microsatellites spanning 23 Mb/24 cM of 19q13. DNA was available from 72 MS patients and 150 unaffected relatives. Parametric and non-parametric linkage analyses did not provide evidence for linkage when all families were tested. After stratifying the families according to HLA-DR15 there was weak evidence for linkage to the 19q13.1 subregion in DR15 negative families (LOD(max)=1.8). Taken together these results do not support a major role of chromosome 19q13.2-q13.3 in MS susceptibility among Finnish MS patients, whereas conclusions on the 19q13.1 subregion are less clear and this region requires further study.

Adolescent↗
PubMed2002

High-resolution carotid artery MRA. Comparison with fast dynamic acquistion and duplex ultrasound scanning.

PURPOSE: To determine whether the diagnostic accuracy of contrast-enhanced MR angiography (CE-MRA) of the carotid arteries is improved by using a slow-injection, high-resolution technique. MATERIAL AND METHODS: In 22 patients suspected to have internal carotid artery (ICA) stenosis at duplex ultrasound scanning (DUS), CE-MRA was performed both with a fast, dynamic (8 s/phase) and with a slower, high-resolution technique (scan time 2:20 min). RESULTS: There was conformity between the CE-MRA techniques regarding the degree of stenosis in 34/40 extracranial ICAs. In 3/6 discrepant cases, short occlusions were seen with the fast dynamic technique, whereas both the high-resolution CE-MRA technique and DUS showed patent vessels. There was an overall tendency toward higher stenosis grading with the dynamic technique. Overlying veins could be removed on a workstation in all high-resolution examinations. CONCLUSION: The high-resolution carotid CE-MRA technique proposed herein seems to improve the diagnostic accuracy, at least for differentiation between high-grade stenoses and occlusions.

Carotid Artery, Internal↗
PubMed2002

Survival of multiple sclerosis in Finland between 1964 and 1993.

The long-term survival of multiple sclerosis (MS) was studied during 1964-1993 in a cohort of 1614 patents in Finland. Survival to death from the initial MS symptoms was analysed by the life-table method, separately for MS related and all causes of deaths. Survival at 40 years was 64% for MS deaths and 53% for all deaths. Higher proportions of violent deaths and neoplasms were observed among MS patients as compared to the general population, whereas the proportion of cardiovascular causes of death was low. MS-related causes accounted for 70% of the recorded 219 deaths. Favourable survival in MS was associated with relapsing-remitting disease course, age at onset below 30 years and optic neuritis or other sensory symptoms at presentation. We were unable to show any significant effect due to calendar time of diagnosis or gender, as the risk of men was similar (risk ratio [RR] = 1.1, confidence interval [CI] 0.8-1.6) as compared to women.

Adult↗
PubMed2001

Increasing prevalence of multiple sclerosis in Finland.

OBJECTIVES: To follow-up the prevalence trends of MS from 1983 to 1993 in western and southern Finland. MS epidemiology has been previously followed from 1964 to 1978 in these regions. The updated prevalences were correlated with incidence trends in the same period. METHODS: Age-adjusted and age-specific MS prevalence rates were calculated for cases classified by Poser's criteria. RESULTS: In the western health-care districts, Seinäjoki and Vaasa, prevalences in 1993 were 202/10(5) and 111/10(5). In the southern district Uusimaa the respective figure was 108/10(5). In Seinäjoki a significant 1.7-fold increase was found in 1993 as compared to 1983, mainly due to increased incidence. In Uusimaa a significant 1.2-fold increase in prevalence was found in the presence of stable incidence. In Vaasa prevalence was stable, although incidence was declining. CONCLUSION: The prevalence of MS is increasing in Seinäjoki and Uusimaa but not in Vaasa. Both the prevalence and incidence in Seinäjoki are now among the highest reported.

Adolescent↗
PubMed2001

On contrast-enhanced magnetic resonance angiography of the aortoiliac arteries.

In contrast-enhanced MR angiography (CE-MRA), vascular signal is produced by the acquisition of a T1-weighted MR imaging scan while the presence of a contrast agent induces a low T1 in blood. In this thesis, CE-MRA of the aortoiliac arteries was evaluated. Different contrast agents and techniques for synchronisation of the scan with the contrast bolus passage were assessed. In 30 patients with clinically suspected iliac artery stenoses, CE-MRA was compared with duplex ultrasound scanning (DUS) and digital subtraction X-ray angiography (DSA), with intra-arterial pressure measurements as reference. No statistically significant differences in sensitivity or specificity were observed between the techniques regarding detection of haemodynamically significant iliac stenoses. The use of multiplanar reformat and source images in the MRA examinations was of value for differentiation between highgrade stenoses and occlusions. With DSA as reference method, MRA had significantly higher sensitivity and specificity than DUS for detection of > or = 50% stenoses. In 14 patients who underwent iliac artery MRA, differences in contrast arrival time of up to 7 s were observed between the aorta and the common femoral artery. A dual-station timing technique adjusting for this difference was found feasible. Compared with a fluoroscopically triggered technique (n = 13), which is used in clinical routine, the dual-station technique was more reliable for the visualisation of distal vessels. In a clinical phase II study comparing doses of the contrast agent gadobenate dimeglumine from 0.0125 to 0.2 mmol/kg b.w. for enhancement of iliac artery MRA, significant improvement in subjective diagnostic quality compared with time-of-flight-MRA was found at all doses from 0.025 mmol/kg b.w. An increasing trend with dose was observed up to a dose of 0.05-0.1 mmol/kg b.w. In a phase I clinical study on the intravascular iron oxide contrast agent NC100150 Injection, a positive dose response was observed for abdominal vascular enhancement, with the highest contrast-to-noise ratio observed at 4.0 mg Fe/kg b.w. at 1.5 T and at 2.5-4 mg Fe/kg b.w. at 0.5 T. At 1.5 T higher calculated R2* values were found for the aorta than for the inferior vena cava.

Academic Dissertations as Topic↗
PubMed2000

Gadolinium-enhanced magnetic resonance angiography, digital subtraction angiography and duplex of the iliac arteries compared with intra-arterial pressure gradient measurements.

PURPOSE: to compare gadolinium-enhanced magnetic resonance angiography (Gd-MRA), digital subtraction angiography (DSA) and duplex of the iliac arteries with intra-arterial pressure gradient measurement as the reference method. MATERIALS AND METHODS: Gd-MRA, DSA and duplex examinations of the iliac arteries were performed in 30 patients (60 arteries) with lower-limb arterial occlusive disease. In 29 arteries, pressure measurements were made (n=25) or the artery was found to be occluded on catheterisation (n=4). An aortofemoral peak systolic pressure gradient of 20 mmHg or more was regarded as haemodynamically significant. Stenoses with a diameter reduction of 50% or more on MRA or DSA, or an increase in peak systolic velocity greater than 150% (duplex) were considered significant. MRA examinations were evaluated by means of maximum intensity projections (MRA-MIP) and using source images and curved multiplanar reconstruction (MRA-MPR). RESULTS: the sensitivity (specificity) for a significant iliac artery stenosis were 81% (75%) for MRA-MIP, 76% (75%) for MRA-MPR, 86% (88%) for DSA, and 72% (88%) for duplex. CONCLUSION: with intra-arterial pressure measurements as the reference method, similar results were achieved with Gd-MRA, DSA and duplex concerning the detection of haemodynamically significant iliac artery stenoses. The use of source images and multiplanar reconstructions resulted in higher accuracy for the detection of occlusions.

Aged↗
PubMed1999

Preattentive bias for emotional information in panic disorder with agoraphobia.

A combined emotional Stroop and implicit memory (tachistoscopic identification) task with 3 types of words (panic-related, interpersonal threat, and neutral words) and 2 exposure conditions (subliminal, supraliminal) was administered to 35 patients with panic disorder and 35 age- and sex-matched controls. The patients showed Stroop interference for panic-related words both sub- and supraliminally and a similar but not equally robust effect on interpersonal threat words. On the tachistoscopic identification task, the patients identified more panic-related words than the controls did but showed no implicit memory bias effect. The patients' subliminal Stroop interference for panic-related words was found to correlate with trait anxiety and depression, although not with anxiety sensitivity.

Adult↗
PubMed1998

Golli-MBP gene in multiple sclerosis susceptibility.

Multiple sclerosis (MS) is an oligo- or polygenic disease but no specific susceptibility genes have been identified so far. In the Finnish population we have previously found evidence for linkage between MS and the myelin basic protein gene (here called Golli-MBP gene) suggesting that either Golli-MBP or another gene in its vicinity contributes to MS suceptibility. Here we have screened the Golli-MBP gene for nucleotide variations and carried out multipoint association analyses in a Finnish case-control data-set as well as in an independent data-set composed of 151 MS families from Finland and Sweden. In both data-sets we found association between MS and alleles in the 1.27 kilobase (kb) range at a tetranucleotide repeat element (TGGA)n which is located 1 kb upstream of the MBP exon 1. Haplotype analyses suggested that the MS-associated 1.27 kb alleles can be split into predisposing and non-predisposing variants and provided evidence that the candidate DNA region contributing to MS susceptibility should be located at the Golli-MBP gene within a 20-25 kb segment that was conserved in the predisposing haplotypes. These findings suggest a role for the Golli-MBP locus in MS susceptibility, at least in a subset of patients, and serve as a basis for highly focused attempts to identify predisposing mutation(s).

Adult↗
PubMed1997

Immune system genes in multiple sclerosis: genetic association and linkage analyses on TCR beta, IGH, IFN-gamma and IL-1ra/IL-1 beta loci.

The role of genetic factors in the etiology of multiple sclerosis (MS) has been clearly demonstrated but the loci determining susceptibility to this disease remain largely unidentified. A contribution from several immune system genes has been suggested based on animal models and association/linkage analyses on MS patients and families. With the exception of the findings from the HLA complex, studies on candidate immune system genes have provided controversial results. Here we have performed genetic association and linkage analyses on four chromosomal regions containing immune system genes. A possible role for each of these loci in MS has been previously suggested. In data-sets derived from the Finnish population we found no evidence for contribution of the T-cell receptor beta chain (TCR beta chromosome 7q35), immunoglobulin heavy chain (IGH chromosome 14q32), interferon-gamma (IFN-gamma chromosome 12q14-q15) or interleukin-1 receptor antagonist/interleukin-1 beta (IL-1ra/IL-1 beta chromosome 2q14-q21) loci in the genetic susceptibility to MS.

Adult↗
PubMed1997

Genomewide scan of multiple sclerosis in Finnish multiplex families.

Multiple sclerosis (MS) is a neurological, demyelinating disorder with a putative autoimmune etiology. It is thought to be a multifactorial disease with a complex mode of inheritance. Here we report the results of a two-stage genomewide scan for loci predisposing to MS. The first stage of the screen, with a low-resolution map, was performed in a selection of 16 pedigrees collected from an isolated Finnish population. Multipoint, non-parametric linkage analysis of the 328 markers did not reveal statistically significant results. However, 10 slightly interesting regions (P = .1-.15) emerged, including our previous findings of the HLA complex on 6p21 and a putative locus on 5p14-p12. Eight of these novel regions were further analyzed by use of denser marker maps, in the second stage of the scan. For the chromosomal regions 4cen, 11tel, and 17q, the statistical significance increased, but not conclusively; for 2q32 and 10q21, the statistical significance did not change. Accordingly, genotyping of the high-density markers in these regions was performed, and the data were analyzed by use of two-point, parametric linkage analysis using the complete pedigree information of the 21 Finnish multiplex families. We detected suggestive evidence for a predisposing locus on chromosomal region 17q22-q24. Several markers on 17q22-q24 yielded positive LOD scores, with the maximum LOD score (Zmax) occurring with D17S807 (Zmax = 2.8, theta = .04; dominant model). Interestingly, a suggestive linkage between MS and the markers on 17q22-q24 was also revealed by a recent genomewide scan in MS families from the United Kingdom.

Autoimmune Diseases↗
PubMed1997

A prospective study of injuries in licensed floorball players.

Injuries occurring among 457 licensed floorball players in the Swedish National League were analysed prospectively during the season from 1993 to 1994. Fifty-one (11%) players sustained 58 injuries. The majority (76%) of the injuries were due to trauma mostly during the gama (55%). Twenty-three (52%) of the traumatic injuries were caused by an opponent or a stick. Ankle sprain (35%) was the most common diagnosis. Injury severity classified with regard to time of absence from sport participation were similarly distributed for minor (36%), moderate (29%) and major (35%) injuries. The total rate of injury was 2.5 per 1000 hours for female and 2.6 for male players. Although this rate is lower than for contact sports like soccer and ice-hockey, we feel that further investigation of floorball injuries and improvement of protection devices would be valuable.

Adult↗
PubMed1996

A putative vulnerability locus to multiple sclerosis maps to 5p14-p12 in a region syntenic to the murine locus Eae2.

Multiple sclerosis (MS) is a chronic inflammatory disorder characterized by multifocal damage of myelin in the central nervous system (CNS). The prevalence of this putative autoimmune disease is 0.1% in individuals of northern European origin. Family, adoption and twin studies implicate genetic factors in the aetiology. MS is widely speculated to be a multifactorial disorder with a complex mode of inheritance. Despite many studies of candidate genes, only an association with HLA-DR2-DQ6 has been generally detected, and the number of susceptibility genes remains unknown. The chronic variant of experimental allergic encephalomyelitis (EAE), a T-cell mediated autoimmune disease in rodents, represents a relevant animal model for MS given the chronic relapsing disease course and inflammatory changes of CNS observed in these demyelinating disorders. Susceptibility to EAE is also influenced by the major histocompatibility complex (MHC). Human syntenic regions to murine loci predisposing to EAE were tested as candidate regions for genetic susceptibility of MS. Three chromosomal regions (1p22-q23, 5p14-p12 and Xq13.2-q22) were screened in 21 Finnish multiplex MS families most originating from a high risk region in western Finland. Several markers yielded positive lod scores on 5p14-p12, syntenic to the murine locus Eae2. Our data provide evidence for a predisposing locus for MS on 5p14-p12.

Animals↗
PubMed1993

Reappraisal of HLA in multiple sclerosis: close linkage in multiplex families.

Although association between multiple sclerosis (MS) and HLA-DR2,DQw6 has been well documented, family studies have not established linkage to HLA. Here we have (1) carried out an HLA-DQA1, -DQB1 association study in unrelated patients and controls, and (2) analyzed linkage between MS and HLA in multiplex families using both nonparametric and parametric methods. The subjects and families were derived from the genetically homogeneous Finnish population, and 14 of the 21 families came from a high-risk area with exceptional familial clustering of cases. In the association study, the frequencies of the alleles DQA1*0102 and DQB1*0602 (encoding DR2-associated DQw6 antigen) were significantly increased in MS patients compared to controls. In the families, we observed that the segregation of MS with DQA1*0102 and DQB1*0602 was not HLA haplotype specific, i.e., these alleles were frequently transmitted to MS relatives on different parental haplotypes. Consequently, we found strong evidence for linkage between MS and HLA only when the haplotype-independent segregation of the MS-associated alleles was controlled. This observation may partially explain the lack of linkage evidence in previous family studies. The highest LOD scores were obtained to the DQA1 locus (LODmax = 6.43, theta = 0.00). The linkage analyses suggest that both the patients' HLA haplotypes may contribute to MS susceptibility. In one of a patient's haplotypes, the susceptibility locus was closely associated with DQA1*0102 and DQB1*0602, whereas in the other haplotype no association with any of the individual candidate loci was found. These results demonstrate, for the first time, a close linkage between MS and HLA, and raise the possibility of distinct HLA-linked susceptibility genes in MS.

Base Sequence↗
PubMed1993

Effect of operative choledochoscopy after choledocholithotomy on the incidence of retained stones.

OBJECTIVE: To see whether the introduction of operative choledochoscopy would lower the incidence of retained stones in the common bile duct. DESIGN: Retrospective study. SETTING: Mora Hospital, Mora, Sweden. SUBJECTS: 176 patients who underwent exploration of the common bile duct from 1984-1991. INTERVENTIONS: After exploration of the common bile duct, 109 of the 176 patients underwent choledochoscopy; the remaining 67 had the choledochotomy closed over the T-tube, and an operative cholangiogram done. RESULTS: Six of the 109 patients (6%) who have had common bile duct exploration followed by choledochoscopy were found to have residual stones and in 1 of those 6 no stones had been found on the exploration of the duct. Ten of the 67 patients (15%) who had choledocholithotomy followed by an operative cholangiogram had residual stones, and in two of those no stones had been found on exploration. The annual frequency of choledochoscopy after exploration of the common bile duct increased from 50% to 80% over the period. CONCLUSION: We recommend that operative choledochoscopy should always be done after exploration of the common bile duct to reduce the incidence of retained stones.

Endoscopy, Digestive System↗
PubMed1992

Genetic susceptibility to multiple sclerosis linked to myelin basic protein gene.

Genetic factors have been implicated in the aetiology of multiple sclerosis (MS), but the genes conferring susceptibility to MS have not been identified. We carried out genetic linkage and association analyses by studying polymorphism of the myelin basic protein (MBP) gene on chromosome 18, a candidate gene for MS, in 21 MS families, 51 additional unrelated patients with definite MS, and 85 controls. All subjects were Finnish, and 14 of the families were from an area with an exceptional familial clustering of MS. Magnetic resonance imaging (MRI) was used to examine subclinical disease in symptom-free family members. In the association analysis, the allele frequencies between MS patients and controls differed significantly, p = 0.000049), the difference being attributable mainly to a higher frequency of a 1.27 kb allele among patients. In the linkage analysis, based on an autosomal dominant model and penetrance 0.05, a maximum LOD score of 3.42 (theta = 0.00) was obtained when patients with optic neuritis and their symptom-free siblings with abnormal MRI findings were classified as "affected". When these subjects were classified as "unknown" the maximum LOD scores ranged from 2.99 to 3.25 (theta = 0.00). The results suggest that in this population genetic predisposition to MS is closely linked to the MBP gene and that polymorphism at the MBP locus or an adjacent locus has a role in the aetiology of MS.

Adult↗