Biomedical subjects

K-M Myhr

Publications and source records attributed to K-M Myhr.

At least 19 recordsLinked to original sources

PubMed2006

A 50-year follow-up of the incidence of multiple sclerosis in Hordaland County, Norway.

OBJECTIVE: To assess longitudinal follow-up of the incidence of multiple sclerosis (MS) through five decades and estimate the prevalence rate in Hordaland County, Norway, on January 1, 2003. METHODS: All patients with MS diagnosed from 1953 to 2003 were identified in the patient records of the Department of Neurology, Haukeland University Hospital, Bergen, Norway. The diagnostic criteria of Poser et al. were applied and only patients with definite and probable MS were included. The study comprises 912 patients, and 666 patients with MS were living in Hordaland on January 1, 2003. The annual incidence rates for the years 1953 to 2003 were calculated. RESULTS: The total crude prevalence rate on January 1, 2003, was 150.8 per 100,000 population: 191.3 per 100,000 among women and 109.8 per 100,000 among men. The annual incidence of MS increased from 1.8 per 100,000 in 1953 to 1957 to 6.0 per 100,000 in 1993 to 1997. CONCLUSIONS: Hordaland County, Norway, has changed from a low-risk to a high-risk area for multiple sclerosis (MS) during the last 50 years. During the last 25 years, the incidence of MS has been stable rather than increasing. Systematic longitudinal follow-up studies are essential to calculate reliable prevalence and incidence rates in MS. The results suggest that both methodologic and environmental factors are essential in determining the distribution of MS.

Adult↗

PubMed2006

The Norwegian Multiple Sclerosis National Competence Centre and National Multiple Sclerosis registry -- a resource for clinical practice and research.

The Norwegian Multiple Sclerosis National Competence Centre was established at the Department of Neurology, Haukeland University Hospital, Bergen in 1996. Promotion of research, supervision and education of doctors and other health care professionals in Norway are the main responsibilities of the Centre. The centre has established national networks for MS care and research and has provided supervision and education of doctors and other health care professionals in Norway. Guidelines for diagnosis and treatment of MS have been established. The National Multiple Sclerosis Registry was established in 1998 and includes by January 2006 50-60% of all MS patients in Norway. Through a national collaboration, the registry aims for inclusion of a biobank unit for collection of cerebrospinal fluid and serum, DNA, and tissue samples.

Biomedical Research↗

PubMed2006

Planned vaginal births in women with multiple sclerosis: delivery and birth outcome.

OBJECTIVE: The objective of this study was to investigate the effect of maternal multiple sclerosis (MS) on delivery and birth outcome in births without planned caesarean section. METHODS: Data were collected from the compulsory Medical Birth Registry of Norway from 1988 to 2002. Intended vaginal births in this time period were 449 births given by MS mothers and 851,060 control births. RESULTS: The MS mothers had a higher rate of induction of labour, and there was a strong trend for slower progression of second stage of labour and increased use of forceps. The MS group had lower birth weight and length of the neonates. The frequency of birth defects and the neonatal mortality were not increased in the MS group. CONCLUSIONS: Maternal MS affects the birth process and the neonate prenatally, even when the births with planned caesarean section are excluded. MS-related neuronal dysfunction linked to the uterus, is postulated as the most likely mechanism.

Body Size↗

PubMed2006

Benign multiple sclerosis.

A small fraction of patients with multiple sclerosis (MS) have a benign course of the disease. The definition of benign MS has been heavily weighted towards physical disability and in particular ambulation. However, patients who are fully ambulatory may still be heavily disabled by non-motor symptoms like fatigue, pain, depression and cognitive dysfunction. These non-motor symptoms should be considered when defining benign MS.

Cognition Disorders↗

PubMed2006

Multiplexed phosphoprotein analysis in immune cells.

Analyzing signaling networks in immune cells is of particular interests in diseases where treatment choices are preferentially immunomodulatory. By combining phospho-specific antibodies with multicolor flow cytometry it is possible to perform quantitative multiparameter analysis of signaling pathways within complex cell populations. Multiplexed phosphoprotein analysis will potentially incorporate environmental factors such as toxins or pathogens and genetic variability of individual patients in a step towards personalized medicine.

Humans↗

PubMed2006

FcgammaR and multiple sclerosis: an overview.

Receptors for the Fc domain of IgG (FcgammaR) play a key role in the immune system by linking the cellular and humoral immune systems. Despite extensive documentation of CNS-specific antibodies in cerebrospinal fluid and plaques in multiple sclerosis (MS) patients, the role of FcgammaR in this disease remains largely unexplored. Studies indicate however, that polymorphisms in some FcgammaR genes and treatment that induces FcgammaR on immune-competent cells could influence disease progression and treatment response.

Animals↗

PubMed2005

Pregnancy, delivery, and birth outcome in women with multiple sclerosis.

Using data from the compulsory Medical Birth Registry of Norway, the authors investigated the effect of maternal multiple sclerosis (MS) on pregnancy, delivery, and birth outcome in 649 births by MS mothers and 2.1 million control births. The mothers with MS had a higher proportion of neonates small for gestational age and also more frequent induction and operative interventions during delivery.

Age Distribution↗

PubMed2005

High dose methylprednisolone induces FcgammaRI on granulocytes in MS-patients.

Immune complexes impinge on receptors for the Fc domain of IgG (FcgammaR) and may thus influence the disease course in multiple sclerosis (MS). We analyzed FcgammaR distribution on monocytes and granulocytes in twenty relapsing-remitting MS patients at baseline, immediately after a five day course of high dose intravenous methylprednisolone (IVMP) treatment and after two months. After a five day course of IVMP the proportion of granulocytes with FcgammaRI was increased, P=0,002. There was no change in FcgammaRII and FcgammaRIII expression. The effect of IVMP on FcgammaRI expression could be important for the clearance of immune complexes in MS.

Adult↗

PubMed2005

Ethnic variations of IL-10 polymorphisms in a Sami and Norwegian population.

Interleukin-10 (IL-10) production is genetically determined and influenced by different polymorphisms in the promoter region of IL-10. These polymorphisms may contribute to the risk and clinical outcome of various infectious and immunological-related diseases. The Samis are the aboriginal inhabitants of Norway and Fennoscandinavia and are ethnically different from the Norwegians. Different distribution of various immune-related diseases among the Samis compared with Norwegians have been reported. This is the first study to evaluate the distribution of IL-10 polymorphisms in the Sami population. Two hundred healthy Samis were genotyped for polymorphisms in the promoter region of IL-10 at region -1082 (G/A), -819 (T/C) and -592 (A/C). The allele frequencies, genotypes and haplotypes were compared with 187 healthy Norwegians. A significantly higher number of the Samis than the Norwegians had the ATA/ATA genotype, whereas the Norwegians displayed a higher frequency of the GCC/GCC genotype (P=0.0057). There was a significant difference in haplotypes in the two populations with a P=0.0024. These findings may be important for the distribution and clinical outcome of various infectious and immune-related disorders in the two populations.

Aged↗

PubMed2005

Mild depression in young adults with cerebral infarction at long-term follow-up: a population-based study.

We sought to evaluate the prevalence of and risk factors for post-stroke depression (PSD) at long-term follow-up in young adults aged 15-49 years with first-ever cerebral infarction in a population-based study. Scores on Montgomery-Asberg Depression Rating Scale (MADRS) were obtained at follow-up (mean time 6.0 years after the stroke) and analysed in subgroups. MADRS scores were obtained in 196 of 209 surviving patients. PSD (MADRS>or=7) was detected in 56 patients (28.6%). None had severe PSD. Alcoholism (P=0.006), depressive symptoms any time before the index stroke (P=0.016), and severe neurological deficits on admission for the index stroke (P=0.043) were independently associated with PSD. PSD seems milder in young ischaemic stroke patients compared with older patients. Alcoholism, depression any time before the index stroke, and severity of neurological deficits on admission for the stroke increased the risk of developing PSD in the long run.

Adolescent↗

PubMed2005

IL-10 promoter haplotype influence on interferon treatment response in multiple sclerosis.

The level of interleukin-10 (IL-10) expression is related to polymorphisms -1082 (G/A), -819 (T/C) and -592 (A/C) in the promoter region of the IL-10 gene, which constitute three haplotypes, GCC, ATA, and ACC. The ATA (a non-GCC) haplotype, which is associated with low IL-10 expression, has been shown to improve interferon (IFN) treatment response in hepatitis C. We analysed the distribution of IL-10 promoter haplotype combinations to determine whether they could influence initial IFN treatment response in 63 patients with relapsing-remitting multiple sclerosis (MS). The patients were grouped into non-GCC or GCC haplotypes, and the clinical and magnetic resonance imaging (MRI) disease activity was compared in the two groups. During the first 6 months of treatment, MS patients with non-GCC haplotypes experienced fewer new MRI T1-contrast enhancing lesions [0.77+/-0.36 (SEM)] than patients with the GCC haplotype (2.45+/-0.57) (P=0.05, Mann-Whitney U test). No differences were detected on clinical disease activity. The results suggest an influence of IL-10 promoter polymorphisms on IFN treatment response in MS.

Adult↗

PubMed2005

Guidelines on use of anti-IFN-beta antibody measurements in multiple sclerosis: report of an EFNS Task Force on IFN-beta antibodies in multiple sclerosis.

Therapy-induced binding and neutralizing antibodies is a major problem in interferon (IFN)-beta treatment of multiple sclerosis. The objective of this study was to provide guidelines outlining the methods and clinical use of the measurements of binding and neutralizing antibodies. Systematic search of the Medline database for available publications on binding and neutralizing antibodies was undertaken. Appropriate publications were reviewed by one or more of the task force members. Grading of evidence and recommendations was based on consensus by all task force members. Measurements of binding antibodies are recommended for IFN-beta antibody screening before performing a neutralizing antibody (NAB) assay (Level A recommendation). Measurement of NABs should be performed in specialized laboratories with a validated cytopathic effect assay or MxA production assay using serial dilution of the test sera. The NAB titre should be calculated using the Kawade formula (Level A recommendation). Tests for the presence of NABs should be performed in all patients at 12 and 24 months of therapy (Level A recommendation). In patients who remain NAB-negative during this period measurements of NABs can be discontinued (Level B recommendation). In patient with NABs, measurements should be repeated, and therapy with IFN-beta should be discontinued in patients with high titres of NABs sustained at repeated measurements with 3- to 6-month intervals (Level A recommendation).

Antibodies↗

PubMed2005

IL-6: an early marker for outcome in acute ischemic stroke.

OBJECTIVES: Inflammation plays an important role in the pathophysiology of stroke. We correlated interleukin (IL)-6, IL-10, C-reactive protein (CRP) and T-lymphocyte subtype levels in acute ischemic stroke patients with stroke volume and clinical outcome. MATERIALS AND METHODS: Blood samples were obtained from 11 patients at defined intervals during 1 year. Nine healthy age-matched subjects served as controls. IL-6, IL-10 and CRP were quantified by enzyme-linked immunosorbent assay and T lymphocytes by flow cytometry. Volume measurement was carried out by computed tomography or magnetic resonance imaging and clinical outcome was scored by the European stroke scale (ESS) and Barthel index (BI). RESULTS: IL-6 levels were increased in the acute phase of stroke compared with healthy controls (P = 0.002) and correlated with larger stroke volume (P = 0.012) and less favorable prognosis after 1 year, measured by ESS (P = 0.014) and BI (P = 0.006). IL-10, CRP and T-lymphocyte subtypes in the acute phase were not correlated with stroke volume or clinical outcome. CONCLUSION: IL-6 seems to be a robust early marker for outcome in acute ischemic stroke.

Acute Disease↗

PubMed2004

Etiology of and risk factors for cerebral infarction in young adults in western Norway: a population-based case-control study.

We sought to study the etiology of and risk factors for cerebral infarction in young adults in Hordaland County, Norway. All patients aged 15-49 years living in Hordaland County with a first-ever cerebral infarction during 1988-97 were included. Etiology was analyzed in subgroups defined by sex, age (<40 years versus >/=40 years), circulation territory (anterior versus posterior circulation) and short-term functional outcome [modified Rankin score (mRS) </= 2 versus mRS > 2]. A questionnaire was used to evaluate possible risk factors amongst the patients compared with an age- and sex-matched control group. The distribution of etiology was significantly different in all subgroups. Atherosclerosis was frequent amongst men (22.8% vs. 4.2%) and patients >/= 40 years (20.8% vs. 2.7%). All patients with microangiopathy had favorable short-term outcome. Significant risk factors were smoking more than 15 cigarettes per day (P < 0.001), hypertension (P = 0.001), and myocardial infarction (P = 0.035). Modifiable risk factors were frequent.

Adolescent↗

PubMed2004

Genes in the HLA class I region may contribute to the HLA class II-associated genetic susceptibility to multiple sclerosis.

In order to analyze whether loci in the human leukocyte antigen (HLA) class I region may contribute to the HLA class II-associated genetic susceptibility to multiple sclerosis (MS), we examined selected microsatellite markers in 177 Nordic sib-pair families, 222 British sib-pair families, 323 sporadic Norwegian MS patients and 386 Norwegian controls. All samples were, in addition, genotyped for the HLA-DR DQ haplotype, and the Norwegian case-control samples were also typed for HLA-A and -B loci. In the Norwegian sporadic MS patients association was seen with HLA-A, HLA-B, and with the D6S265 marker, located 100 kb centromeric to HLA-A. Associations with HLA-A and D6S265 loci were also suggested when restricting the analysis to HLA-DR15 haplotypes. In the sib-pair data a similar trend was seen with marker D6S265. Higher genotypic relative risk (GRR) was found for individuals who carry both HLA-DR15 and -A3 (GRR = 15), compared to those who carry only HLA-DR15 (GRR = 7), only HLA-A3 (GRR = 3) or none of these alleles (GRR = 1). The highest risk was conferred by a combination of HLA-DR15 and -A3 (odds ratio (OR) = 5.2). These results suggest that HLA-A or a gene in linkage disequilibrium with it may contribute to the HLA class II-associated genetic susceptibility to MS.

Case-Control Studies↗

PubMed2004

The effects of interferon-alpha2a on concentrations of immunoglobulins, complement and lymphocytes in patients with multiple sclerosis.

Multiple sclerosis (MS) patients treated with type I interferon experience reduced disease activity. Because immunoglobulins (Igs), complement and lymphocytes have been given a role in the pathogenesis of MS, we investigated the longitudinal effect of interferon-alpha2a (IFNA) on the variability of these parameters. Patients were treated for 6 months with 4.5 million international units (MIU) IFNA (24 patients), 9.0 MIU IFNA (21 patients) or placebo (23 patients). IFNA induced a significant increase in concentrations of total IgG and IgG subclasses 1, 3 and 4. At 6 months, the mean concentration of IgG had increased by 1.51 g/l (CI: 0.82, 2.21) in the 9.0 MIU IFNA group. There was no significant effect of IFNA treatment on concentrations of IgG2 and IgA, while the effect on IgM was borderline significant. After 6 months, IgM had increased by 0.29 g/l (CI: -0.01, 0.65) in the 9.0 MIU IFNA group. IFNA induced a significant increase in the concentration of C1 inhibitor (INH). At 3 months, the mean concentration of C1 INH had increased by 0.033 g/l (CI: 0.01, 0.05). At 3 months, C4 had increased by 0.05 g/l (CI: 0.01, 0.09) in the 9.0 MIU IFNA group. The effect of IFNA on C4 was inconclusive but indicates an effect during the initial phase of the treatment. C3 showed no significant treatment-mediated change. IFNA induced a significant decrease in lymphocyte concentrations by 0.56 x 106 lymphocytes/ml (CI: -0.81, -0.31) at 3 months. There were no significant associations between changes in immune parameters and changes in clinical and magnetic resonance imaging scores. The results verify that IFNA modulates and activates both the innate and the adaptive arms of the immune system. The observations should be of relevance when evaluating mechanisms of action of IFN treatment in MS.

Antineoplastic Agents↗

PubMed2004

Pain and sensory complaints in multiple sclerosis.

Pain is a frequent and disabling symptom among multiple sclerosis (MS) patients. The importance of this problem was investigated in a hospital based MS population. A total of 142 MS patients underwent neurological examination and a structured interview for registration of pain and sensory symptoms. One-hundred and five patients reported sensory and/or pain symptoms. Pain was reported by 93 patients and was most frequently located in the limbs and lumbar region. The presence of pain was independent of gender, age at onset and examination, disability, disease course and duration. The most frequently reported characteristics of the symptoms were paresthesia, neuralgia and deep muscular aching. About 40% of the patients reported that the symptoms had important influence on daily activities. Only one-third of the patients were treated for their pain. Pain is a frequent and disabling symptom, independent of demographic and clinical variables in MS patients. The low frequency of treatment for these symptoms indicates a need for improved attention to this problem.

Adult↗

PubMed2004

Long-term outcome of cerebral infarction in young adults.

OBJECTIVES: We analysed the long-term outcome of 232 young adults aged 15-49 years with first-ever cerebral infarction in 1988-1997 in western Norway. MATERIAL AND METHODS: Mortality, recurrence, epilepsy, functional state as evaluated by modified Rankin scale (mRS), and employment were analysed at follow-up (mean time 5.7 years). RESULTS: Twenty-three (9.9%) patients had died. Recurrence occurred in 9.9%, and post-stroke seizures developed in 10.5%. Recurrence was associated with diabetes mellitus (P = 0.005). Favourable functional outcome (mRS = 2) was found in 77.9%. The functional outcome was better in posterior than anterior circulation infarctions (P = 0.011). Unfavourable functional outcome (mRS > 2) was associated with diabetes mellitus (P = 0.001) and severity of neurological deficits on admission for the index stroke (P < 0.001). Only 58.3% were employed at follow-up. CONCLUSION: This population-based study shows that, although the majority had favourable functional outcome, cerebral infarction had major long-term impact on young adults as evaluated by mortality, recurrence and employment status.

Adolescent↗