Search PubMed⌕ Search

Biomedical subjects

H Nyland

Publications and source records attributed to H Nyland.

At least 37 records · Page 2Linked to original sources

Altered antibody pattern to Epstein-Barr virus but not to other herpesviruses in multiple sclerosis: a population based case-control study from western Norway.

OBJECTIVE: The prevalence of anti-EBV antibodies was studied in a group of 144 patients with multiple sclerosis and 170 age, sex, and area matched controls from the county of Hordaland, western Norway. The prevalence of three other herpesviruses, herpes simplex virus (HSV), varicella zoster virus (VZV), and cytomegalovirus (CMV), were also included. METHODS: Antibodies to various virus antigens were determined by enzyme linked immunosorbent assay (ELISA) and indirect immunfluorescence (IIF) in serum samples from 144 patients with multiple sclerosis and 170 controls. RESULTS: All of the 144 patients with multiple sclerosis had IgG antibodies to EBV compared with 162 of 170 controls (p=0.008). The frequency of IgG antibodies to EBV capsid antigen (VCA), nuclear antigen (EBNA), and early antigen (EA) was significantly higher in patients with multiple sclerosis compared with the controls (p<0.000001, p=0.01, and p<0.0001 respectively). The presence of antibodies was independent of the initial course of the disease and the disease activity at the time of blood sampling. The prevalence of IgG antibodies to HSV, CMV, and VZV did not differ between cases and controls. CONCLUSION: The results suggest a role for EBV in the aetiology of multiple sclerosis.

Adolescent↗

The long-term prognosis of Guillain-Barré syndrome. Evaluation of prognostic factors including plasma exchange.

Fifty-two patients with Guillain-Barré syndrome (GBS) were re-examined 1-14 years (median 7 years) after the initial onset of symptoms. At the follow-up 38 patients (73%) reported being completely symptom-free. Neurological examination revealed that 11 patients (21%) had motor and 16 patients (31%) had sensory signs, mainly distal in the lower limbs. One patient (2%) had cranial nerve signs. Fifteen patients (29%) had areflexia, generally of the ankle jerks. Severe pareses (high maximal disability grade), long duration of maximal symptoms and recovery were significantly associated with persistent disability. Age, sex, preceding infection, latency between infection and the onset of disease, weakness as an initial symptom, autonomic dysfunction, speed of progression, electro-physiological signs of axonal degeneration, cerebrospinal-fluid protein concentration and treatment with plasma exchange did not significantly influence the disability grade at follow-up.

Disability Evaluation↗

Impairment, disability, and handicap in multiple sclerosis. A cross-sectional study in an incident cohort in Møre and Romsdal County, Norway.

We conducted a cross-sectional, geographically based study of functional status in an incident cohort of 124 multiple sclerosis (MS) patients with onset of disease from 1 January 1976 to 31 December 1986 in Møre and Romsdal County, Norway. The cohort comprised 58 men (46.8%) and 66 women (53.2%). One hundred and thirteen patients (91.1%) had a primary remitting course of disease and 11 (8.9%) had primary progressive MS. The mean age of onset was 33.3 years (range 14-64), and the mean duration of disease 7.8 years (range 1-23). The Minimal Record of Disability (MRD) of multiple sclerosis was applied to measure the degree of impairment, disability and handicap. The mean Kurtzke Expanded Disability Status Scale (EDSS) score was 3.76 (0-10), and the frequency distribution of the EDSS scores in the cohort was bimodal. Twenty-eight (22.6%) patients in the cohort had marked paraparesis, paraplegia of quadriplegia. Nineteen patients (15.3%) had frequent urinary incontinence, need for almost constant catheterization, or need for constant use of measures to evacuate stools. Five patients (4%) had a severe decrease in mentation or dementia. Forty-eight patients (38.7%) reported frequent problems with fatigue or fatigability preventing sustained physical function. Less than half of the cohort (42.7%) was working full-time, and 49.2% of the patients reported that they received external support to maintain their usual financial standard. Lack of ability to work full-time and accordingly the dependence upon external financial support were significantly associated with the primary progressive course of disease. Fatigue was statistically significantly related to lack of working ability. The estimated cost of MS in the county in 1991 was 48.2 million NOK (approximately 7.531.250 US $) based on the cost-of-illness methodology.

Adult↗

An Epstein Barr virus-related cross reactive autoimmune response in multiple sclerosis in Norway.

In studies of patients in Norway with multiple sclerosis (MS), we have found cross reactive autoantibodies related to the Epstein Barr virus nuclear antigen-1 (EBNA-1). The MS patients had elevated IgG antibody to EBNA-1, as measured by reactivity with a synthetic glycine/alanine peptide, P62, which represents the glycine/alanine repeat in EBNA-1. The mean titer of anti-P62 in patients with acute relapse at the time of assay was significantly higher than in the remaining patients. Patients with remitting/relapsing MS also had elevated autoantibody to a lymphocyte protein, p542, cross reactive with EBNA-1 through a glycine/serine epitope. High titered anti-EBNA-1 antibodies from some MS, as well as from some SLE sera, were shown to cross react with 80-82 kDa and 60 kDa proteins in neuroglial cells.

Amino Acid Sequence↗

Incidence of multiple sclerosis in Møre and Romsdal, Norway from 1950 to 1991. An age-period-cohort analysis.

We have examined the time trends in multiple sclerosis incidence over the past four decades from 1950 to 1991 in Møre and Romsdal County, Norway. Incidence rates by year of birth, year of onset and year of diagnosis according to sex, age and clinical course were studied. All patients with multiple sclerosis diagnosed by August 1992 were included, giving a total of 419 patients (171 men, 248 women) with onset of multiple sclerosis in the period 1950-91. Mean age at onset was 33.2 years, and mean age at diagnosis was 39.2 years. The incidence rate by year of onset increased from 2.87 per 100 000 in the period 1950-54 (men 3.06, women 2.67) to 5.57 per 100 000 in 1985-91 (men 3.75, women 7.94) (P<0.001). The incidence was particularly high in the period from 1975 to 1985. Major period- or cohort-effects in incidence, apart from the general increasing trend, could not be identified by an age-period-cohort analysis.

Adolescent↗

Disability and mortality in multiple sclerosis in western Norway.

INTRODUCTION: Continued studies of frequency trends in carefully selected sites around the world can provide clues to the cause of multiple sclerosis (MS). MATERIAL AND METHODS: Based on information from three different, semi-independent sources of information, we have examined the temporal trends in the average annual age-adjusted rates of disability pension incidence, mortality, and incidence of MS from 1966 to 1991 in Møre and Romsdal County, Norway. RESULTS: The average annual age-adjusted disability pension incidence rates (1966-68 = 3.62/100,000; 1990-91 = 7.33/100,000), the mortality rates (1966-68 = 0.91/100,000; 1990-91 = 1.88/100,000), and the incidence rates (1966-68 = 4.22/100,000; 1990-91 = 5.02/100,000) all showed a statistically significant increase. The difference in the development of MS-specific disability pension prevalence rates in the county compared to the nation is notable. CONCLUSIONS: We consider that the increase in disability pension incidence, mortality, and incidence of MS is of biological significance. Thus three different sources of information corroborate corresponding trends indicating that better case ascertainment and improved diagnostic facilities only partially can explain the reported MS increase in western Norway.

Adolescent↗

Multiple sclerosis and chronic inflammatory diseases. A case-control study.

INTRODUCTION: Disease associations may provide useful etiological leads in relation to diseases of unknown cause. MATERIAL AND METHODS: We conducted a hospital-based case-control study of 155 MS patients and 200 controls in Hordaland County, Norway to investigate the possible association between MS and autoimmune diseases. RESULTS: The MS patients had a statistically significant more frequent coexistence of rheumatoid arthritis, psoriasis, and goitre when compared to the controls (OR = 2.96; 95% CI 1.23-7.66). This difference persisted when analysing the definite MS cases separately (OR = 2.90; 95% CI 1.10-7.96). The familial occurrence of chronic inflammatory diseases was not significantly different in cases and controls. A significant increased risk to develop MS occurred in first degree relatives of MS patients (OR = 12.58; 95% CI 1.73-552). CONCLUSION: Acknowledging the low figures, the uncertain estimates with large confidence intervals, and thus the obvious role of chance in this study, the results might indicate that a generalized, genetically controlled problem of the immune system could result in aggregates of the reported diseases, all of which are partly characterized by aberrations of the immune system.

Adolescent↗

Multiple sclerosis and cancer in Norway. A retrospective cohort study.

INTRODUCTION: During the extended course of multiple sclerosis (MS) there are ample opportunities for the patients to develop other illnesses including cancer, a potential long-term complication of the immunosuppressive drug treatment in MS. MATERIAL AND METHODS: A retrospective cohort study was done to estimate the relative risk of cancer in a population of MS-patients from three Norwegian counties by record linkage with the Cancer Registry of Norway. The cohort comprised 1271 MS-patients, 530 men and 741 women, identified in five longitudinal population-based incidence studies. The reporting of cancer cases has been compulsory in Norway since 1952. RESULTS: We found 73 cancer cases (standardized incidence ratio (SIR) = 0.86, 95% CI 0.68-1.09). Mean follow-up time was 18.4 years. A significant excess of breast cancers was observed (SIR = 1.70, 95% CI 1.05-2.60). A non-significant excess of cancer in the urinary tract was observed. No significantly increased risk in hematologic and lymphatic malignancies or malignant brain tumors was observed. The incidence of cancer of the digestive organs was significantly lower than expected (SIR = 0.51, 95% CI 0.24-0.93). CONCLUSION: Overall, the study indicates that an MS-patient is not at any unusual risk for subsequent development of cancer compared to the normal population.

Adult↗

Guillain-Barré syndrome in northern Tanzania: a comparison of epidemiological and clinical findings with western Norway.

To study Guillain-Barré syndrome (GBS), the clinical files of GBS patients, 59 in northern Tanzania (1984-1992) and 56 in western Norway (1980-1992), were retrospectively reviewed and compared. The average annual incidence rate for GBS in the Kilimanjaro region was 0.83/100,000 population as compared to 1.2/100,000 reported in western Norway (25). GBS patients in the Tanzanian series were younger, had less antecedent infection and were a longer time interval from onset to admission and in hospital. On examination arm and sensory involvement were less common and urinary sphincteric involvement more common in the Tanzanian series. The overall mortality rate was higher in the Tanzanian series, 15.3% (9/59) versus 1.8% (1/56). HIV infection was found in 30.5% (11/36) of GBS patients in the Tanzanian series as compared to 3.4% (161/4687) in corresponding blood donors. There was no evidence of HIV infection in the Norwegian series. The HIV-seropositive GBS patients in comparison with HIV seronegatives had a shorter duration of onset, greater neurological involvement and a higher mortality rate, 45.5% (5/11) versus 16% (4/21). This study shows that apart from minor clinical differences and an increased mortality rate in the Tanzanian series GBS was similar in both series. GBS in the Tanzanian series was strongly associated with HIV infection, and seropositives by comparison with seronegatives appeared to have more severe disease.

AIDS-Related Opportunistic Infections↗

Proton MR spectroscopy and MR imaging in acute and chronic multiple sclerosis--ringlike appearances in acute plaques.

PURPOSE: We wanted to compare the metabolite status of brain lesions in different clinical subtypes of multiple sclerosis (MS). Two acute MS lesions with ringlike appearances were also investigated. MATERIAL AND METHODS: Twenty-three clinically stable MS patients, 2 patients with acute relapses, and 15 healthy individuals were examined by MR imaging and localized proton MRS. RESULTS: No metabolite differences were seen in plaques of different subtypes. Decreased NAA/Cr and NAA/choline ratios as well as increased inositol/Cr ratios were observed in the plaques of the clinically stable or chronic active MS patients as compared with controls. The ring plaques had hyperintense cores with surrounding halos, separated from the cores by rings with low signal intensity in T2-weighted images. The core exhibited a prolonged T2 relaxation time. Proton spectra initially contained lactate. CONCLUSION: No differences between the metabolite status of nonacute plaques in different clinical subtypes could be detected. The ring plaques contained lactate signals indicating oedema, inflammation, and macrophage invasion, and may be transition forms between acute oedematous lesions and chronic demyelinated plaques.

Adult↗

Treatment of relapsing-remittent multiple sclerosis with recombinant human interferon-alfa-2a: design of a randomised, placebo-controlled, double blind trial in Norway.

A multicentre, randomised, double-blind, placebo controlled study to evaluate the efficacy and safety of 4.5 and 9.0 MIU recombinant human interferon alfa-2a (Roferon-A) given thrice weekly in patients with relapsing-remittent multiple sclerosis is described. The patients are treated for 6 months followed by a 6 months drug-free period. The primary objective is to determine new disease activity analysed by monthly MRI with gadodiamide (GdDTPA-BMA, Omniscan). The study is conducted at eight centers in Norway and is completed in January 1996.

Contrast Media↗

Bladder, bowel and sexual dysfunction in patients with multiple sclerosis--a cohort study.

A population-based cohort study focusing on bladder, bowel and sexual dysfunction in MS-patients was performed. The total cohort under study comprised 209 patients. The duration of the disease was nine to 19 years. A total of 57.5% reported some to major bladder dysfunction. The corresponding figures of bowel and sexual dysfunction were 41.3% and 51% respectively. The dysfunction increased with higher age, higher age at onset of MS, duration and course of the disease. The most unfavourable course of the disease was the relapsing remittent secondary progressive form, where almost 70% became worse during an eight year's observation period, in contrast to patients with the relapsing remittent form, where less than 30% became worse. The study shows that a high number of MS patients is in need of a neuro-urological work-up, and that effort should be made to prevent or delay a secondary progressive course of the disease.

Adult↗

[Multiple sclerosis].

Multiple sclerosis is a chronic inflammatory disease of the central nervous system which affects young and middle-aged adults. The clinical symptoms and course vary considerably; most patients experience a relapsing-remittent course which may become secondary progressive, a benign course with a favourable prognosis is seen in 30-40%. 10-15% experience a primary progressive course, with a less favourable prognosis. Magnetic resonance imaging, MRI, has become the most important paraclinic investigation and MRI with paramagnetic contrast enhancement reveals "subclinical" disease activity. Demyelination is caused by phagocytosis of microglial cells which appear to be activated by cytokines produced by T helper cells. A delayed type autoimmune response to myelin antigens is probably involved, initiated by a viral infection. Immunosuppressive treatment, corticosteroids and interferons have been shown to affect the MRI behaviour, and reduce the frequency of relapse. The effect on the natural course of the disease has been less convincing and no treatment will reverse long standing neurological dysfunction.

Adrenal Cortex Hormones↗

Prognostic factors for survival in multiple sclerosis: a longitudinal, population based study in Møre and Romsdal, Norway.

A longitudinal, population based study of life expectancy in multiple sclerosis was performed in the county of Møre and Romsdal, Norway during the period 1950-84. A total of 251 patients with multiple sclerosis (110 men, 141 women, mean age at onset of disease 33.6 years) were included. The mean follow up time was 18.1 years. At the end of the study period 70 patients had died. Fifty four (77.1%) of these had multiple sclerosis as the underlying or contributing cause of death on the death certificates. Young age at onset, initial remitting clinical course, and the presence of sensory symptoms at onset were significantly associated with longer survival.

Adolescent↗

Reactive microglia in multiple sclerosis lesions have an increased expression of receptors for the Fc part of IgG.

Receptors for the Fc part of IgG, FcRI (CD64), FcRII (CD32), and FcRIII (CD16) were studied by indirect immunoperoxidase staining of cryostat sections from normal and multiple sclerosis (MS) brains. Microglia in the parenchyma of normal white matter had a dendritic morphology, and were weakly stained by monoclonal antibodies (mAbs) to FcRI, FcRII, and FcRIII. In active MS lesions reactive microglia were strongly stained by the mAbs 32.2 (FcRI), IV-3 (FcRII), and 3G8 (FcRIII). Perivascular macrophages were stained by all anti-FcR mAbs in both normal white matter and in MS lesions, whereas endothelial cells were stained by the anti-FcRIII mAb only. The FcR on microglia and perivascular macrophages may be of functional importance in antibody-dependent cell-mediated cytotoxicity (ADCC), phagocytosis, and local immunoregulation. FcR on endothelium may be of importance in binding and transportation of immune complexes into the CNS. FcR mediated functions may consequently be highly relevant to the pathogenesis of MS.

Adult↗

Detection of MHC class II-antigens on macrophages and microglia, but not on astrocytes and endothelia in active multiple sclerosis lesions.

Tissue sections of brains from patients with multiple sclerosis (MS) and from control individuals were immunostained with MHC class II and glial or vascular endothelial cell antibodies and analyzed by confocal microscopy. MHC class II was abundant in and around actively demyelinating MS lesions and was detected on microglia, phagocytic macrophages, and perivascular macrophages. Astrocytes and vascular endothelial cells were MHC class II-negative. Changes in the size and shape of MHC class II-positive cells associated with MS lesions suggest that microglia transform into phagocytic macrophages, and that they are actively involved in demyelination. Many MHC class II-positive perivascular macrophages within MS lesions contained abundant intracellular MHC class II immunoreactivity; these cells may be involved in antigen presentation and in T cell activation.

Adolescent↗

Fc receptor for IgG (FcR) on rat microglia.

Receptor for IgG (FcR) was demonstrated on rat microglia in vivo and in vitro by immunohistochemical staining with immune complexes of horseradish peroxidase (HRP) and rabbit IgG anti-HRP. Astrocytes, oligodendrocytes and neurons did not express FcR. Microglia in culture also showed FcR-mediated agglutination and phagocytosis of IgG-sensitized erythrocytes. A radiolabelled cDNA probe for rat FcRIII hybridized with a 1.4-kb RNA band in Northern blots prepared from total RNA from rat brain. FcRIII mRNA-positive cells in rat brain, presumably microglia, were demonstrated by in situ hybridization. FcR participates in the initiation of cytotoxic responses and of phagocytosis by microglia and is therefore likely to be important in mediating immune reactions in the brain.

Animals↗

Fc receptors for IgG on cultured human microglia mediate cytotoxicity and phagocytosis of antibody-coated targets.

We have utilized surgically resected human central nervous system (CNS) tissue to determine the expression and functions of Fc receptors (Fc gamma R) on individual cell types found within the CNS. We observed all three classes of Fc gamma R on microglial cells in situ and in vitro, but not on astrocytes or oligodendrocytes. Incubation of cultured microglia with immune complexes (antibody-coated red blood cells) induced phagocytosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and oxidative bursts. We also found that microglia have the capability to produce T cell stimulatory soluble mediators after Fc gamma R crosslinking. These functional responses were enhanced by pretreatment of the microglia with interferon-gamma (IFN-gamma). Our results implicate microglial effector responses triggered by interaction of Fc gamma R with opsonized antigens as potential mediators of tissue injury within the CNS. Such injury may be particularly applicable to multiple sclerosis, an inflammatory demyelinating disease characterized by intrathecal production of immunoglobulins and cytokines.

Adult↗