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At least 649 records · Page 36Linked to original sources
PubMed1990

Mast cells and multiple sclerosis: a light and electron microscopic study of mast cells in multiple sclerosis emphasizing staining procedures.

In the brains of 7 patients with multiple sclerosis, mast cells were observed within the demyelinated plaques, in the border zone of the plaques as well as in seemingly normal white matter. The cells were mostly located in close connection with small vessels. The routine staining with toluidine blue for the demonstration of mast cells is not adequate as compared with staining of similar sections in pinacyanol erythrosine. Mast cells may be a hitherto underestimated contributor to the demyelinating process of multiple sclerosis.

Brain↗
PubMed1998

Extended use of glatiramer acetate (Copaxone) is well tolerated and maintains its clinical effect on multiple sclerosis relapse rate and degree of disability. Copolymer 1 Multiple Sclerosis Study Group.

When 251 relapsing-remitting patients with multiple sclerosis were randomized to receive daily subcutaneous injections of glatiramer acetate, previously called copolymer 1 (Copaxone; n = 125) or placebo (n = 126) for 24 months, there were no laboratory abnormalities associated with glatiramer acetate treatment and it was well tolerated with few side effects. Patients receiving glatiramer acetate had significantly fewer relapses and were more likely to be neurologically improved, whereas those receiving placebo were more likely to worsen. This study was extended for 1 to 11 months (mean of 5.2 months for the glatiramer acetate group and 5.9 months for the placebo group). The blinding and study conditions used during the core 24-month study were unchanged throughout the extension. The results of this extension study confirm the excellent tolerance and safety profile of glatiramer acetate for injection. The clinical benefit of glatiramer acetate for both the relapse rate and for neurologic disability was sustained at the end of the extension trial.

Adult↗
PubMed1990

Efficacy and toxicity of cyclosporine in chronic progressive multiple sclerosis: a randomized, double-blinded, placebo-controlled clinical trial. The Multiple Sclerosis Study Group.

Patients with clinically definite multiple sclerosis, mild to moderately severe neurological disability (entry score on the Expanded Disability Status Scale (EDSS) between 3.0 and 7.0), and a progressive course defined by an increase in the EDSS of between 1 and 3 grades in the year prior to entry were randomized to receive either cyclosporine (n = 273) or placebo (n = 274) in a 2-year, double-blinded, multicenter trial. Treatment groups at entry proved balanced for age, gender, duration of illness, and neurological disability. Cyclosporine dosage was adjusted for toxicity and a median trough whole-blood level was maintained between 310 and 430 ng/ml. The mean increase in EDSS score was 0.39 +/- 1.07 grades for cyclosporine-treated patients and 0.65 +/- 1.08 grades for placebo-treated patients from entry until the time of early withdrawal or completion of the study (p = 0.002). Of three primary efficacy criteria, cyclosporine delayed the time to becoming wheelchair bound (p = 0.038; relative risk, 0.765), but statistically significant effects were not observed for "time to sustained progression" or on a composite score of "activities of daily living." Active treatment did have a favorable effect on several secondary measures of disease outcome. A large and differential withdrawal rate (44% for cyclosporine-treated patients, 32% for placebo-treated patients) complicated the analysis but did not appear to explain the observed effect of cyclosporine in delaying disease progression. Multivariate analysis did not show institutional effects but did demonstrate substantial effects of baseline neurological disability on outcome. Nephrotoxicity and hypertension were common troublesome toxicities and accounted for most of the excess loss of patients in the cyclosporine arm of the study. Thus, chronic cyclosporine therapy was associated with a statistically significant but clinically modest delay of progression of disability in a group of patients with multiple sclerosis selected for moderately severe and progressive disease. Close supervision by physicians familiar with cyclosporine is mandatory to minimize known adverse effects, particularly nephrotoxicity, when considering the use of this immunosuppressant.

Adult↗
PubMed1975

Monozygous twins discordant for multiple sclerosis. Report of one pair and discussion of possible causes of multiple sclerosis.

One pair of male monozygous twins was examined: only 1 twin had multiple sclerosis. Differences in the life histories of the twins were identified. Haematological, biochemical and microbiological studies were performed. It is possible in theory to determine which environmental factors may have been responsible for the development of multiple sclerosis in 1 twin. Several differences in life history were found in this study.

Diseases in Twins↗
PubMed1988

Histocompatibility antigens in multiple sclerosis patients participating in a multicentre trial of azathioprine. British & Dutch Multiple Sclerosis Azathioprine Trial Group.

The human leucocyte antigen (HLA) types of 283 patients with multiple sclerosis participating in a trial of azathioprine treatment were studied. The prevalence of HLA types was compared with those of over 3,300 controls from tissue typing centres in the UK. The prevalence of HLA A3 (38.5% cp 26.1%), HLA B7 (44.9% cp 27.3%) and HLA DR2 (58.3% cp 30.6%) was increased in the multiple sclerosis patients compared with the controls. Age at onset, disease status (relapsing-remitting or currently progressive) and disease severity did not show an association with any particular HLA type.

Adolescent↗
PubMed1989

The characteristics of a national register of people with multiple sclerosis (MS): a comparison between the ARMS (Action for Research into Multiple Sclerosis) register and 10 British MS populations.

Problems with case ascertainment in epidemiological research on multiple sclerosis (MS) make it necessary to use indirect sources. However, there is a lack of information about the characteristics of cases drawn from different sources and thus little basis on which sampling frames for large scale surveys may be constructed. The characteristics of a population drawn from the membership of Action for Research into Multiple Sclerosis (ARMS) were compared with those of 10 other British MS populations reported between 1980 and 1987. Demographic variables examined were geographical location, nationality, ethnicity, sex ratio and age. Diagnostic status, age at diagnosis and duration since diagnosis were considered together with data on the comparative populations based on date of onset. On all the variables investigated the ARMS population fell close to or within the range shown by the comparative populations. The relative youth of the ARMS population and its bias towards a high proportion of females were differences in keeping with existing knowledge about the membership of mutual support organisations. A population drawn from such an organisation may usefully complement other MS research populations provided that the likely biases in each are understood.

Adult↗
PubMed2004

[Multiple sclerosis: treatment and prevention of relapses and progression in multiple sclerosis].

The benefit of interferon beta-1a and 1b treatment on relapsing remitting multiple sclerosis (MS) is now firmly established. IFN beta-1b, the only disease modifying drug approved in Japan, was comparably effective in OS-MS and C-MS in a Japanese treatment trial. Although the effect of Copaxone is less conclusive, superior safety profiles make this treatment an important alternative choice. Mitoxantrone has been approved by FDA for rapidly progressing patients. The usage should be restricted for two or three years to avoid cardiac side effects. Antegren, which is an anti-cell adhesion molecule monoclonal antibody and has been shown to be very effective for relapsing MS patients, now awaits approval by FDA. Many combination therapies are currently under systematic survey and hoped to provide superior efficacy.

Disease Progression↗
PubMed2003

Interleukin (IL)-1 gene polymorphisms: relevance of disease severity associated alleles with IL-1beta and IL-1ra production in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune disorder, with a considerable genetic influence on susceptibility and disease course. Cytokines play an important role in MS pathophysiology, and genes encoding various cytokines are logical candidates to assess possible associations with MS susceptibility and disease course. We previously reported an association of a combination of polymorphisms in the interleukin (IL)-1B and IL-1 receptor antagonist (IL-1RN) genes (i.e. IL-1RN allele 2+/IL-1B(+3959)allele 2-) with disease severity in MS. Extending this observation, we investigated whether IL-1beta and IL-1ra production differed depending on carriership of this gene combination. METHODS: Twenty MS patients and 20 controls were selected based upon carriership of the specific combination. In whole blood, in vitro IL-1beta and IL-1ra production was determined by enzyme-linked immunosorbent-assay after 6 and 24 h of stimulation with lipopolysaccharide. RESULTS: Carriers of the specific combination produced more IL-1ra, especially in MS patients, although not significantly. IL-1ra production was significantly higher in individuals homozygous for IL-1RN allele 2. In patients, Il-1ra production was higher and IL-1beta production lower compared with controls. In primary progressive patients, the IL-1beta /IL-1ra ratio was significantly lower than in relapsing-remitting patients. CONCLUSION: Our results suggest higher in vitro IL-1ra production in carriers of IL-1RN allele 2, with an indication of an allelic dose-effect relationship.

Adult↗
PubMed1996

Comparative evaluations of neuroperformance and clinical outcome assessments in chronic progressive multiple sclerosis: I. Reliability, validity and sensitivity to disease progression. Multiple Sclerosis Study Group.

There remains controversy regarding the most sensitive and valid outcome assessments to use in multiple sclerosis (MS) clinical trials. A double blind, placebo controlled, parallel group multicenter clinical trial to evaluate the clinical efficacy of cyclosporine A in chronic progressive MS incorporated several major clinical and performance outcome assessment modalities and a large sample size, both of which provide a unique opportunity to explore the relationship among MS disease status and the various outcome measures over time. The measures included a structured neurological examination, the Kurtzke Functional System scales and Expanded Disability Status Score, and the Incapacity Status Scale from the MS Minimal Record of Disability, the Harvard Ambulation Index, and neuroperformance testing. A test-retest reliability index, principal component analyses and a signal-to-noise ratio metric were used to comparatively evaluate the reliability, validity and sensitivity to disease progression of the various outcome assessments. The goal was to provide a rational basis for selection of behavioral outcome assessments in future MS clinical trials by identifying the primary dimensions of MS measured by the candidate outcome assessments and providing an objective basis for selecting tests that are most sensitive to MS disease and its progression over a two year trial period. We conclude that the components of the major clinical and performance measures show excellent reliability and cross validation. Principal component analyses of all outcome assessments yielded six primary underlying factors for describing disease status in chronic progressive MS that included lower extremity/pyramidal dysfunction, cerebellar/brainstem and upper extremity dysfunction, somatosensory dysfunction, visual dysfunction, mental or intellectual dysfunction and bowel/bladder problems. Signal-to-noise ratios indicated that upper and lower extremity composites of neuroperformance test items provided the most sensitive indicators of MS disease progression in the placebo group over the 2 year trial period.

Activities of Daily Living↗
PubMed2000

A questionnaire assessment of unmet needs for rehabilitation services and resources for people with multiple sclerosis: results of a pilot survey in five European countries. Needs Task group of MARCH (Multiple Sclerosis and Rehabilitation, Care and Health Services Research in Europe).

OBJECTIVE: To develop an international services and needs assessment instrument (SUN) for people with multiple sclerosis and their carers and to pilot this in different countries of the European Community. DESIGN: Interview study of people with multiple sclerosis, their carers and nominated key professionals examining the unmet needs of patients and carers. SETTING: Belgium, Estonia, Greece, Italy and the United Kingdom. MAIN OUTCOME MEASURES: Needs assessment questionnaire. RESULTS: The study comprised 137 people with multiple sclerosis, 125 carers and 111 professionals. Patients reported on average 2.9 unmet needs for themselves; their carers and professionals reported on average 2.4. Needs were categorized into seven broad categories. Due to difficulties experienced by the local researchers in distinguishing between needs and objectives a large proportion of needs had to be assigned to the 'other' category. CONCLUSIONS: The SUN is a valuable and practicable tool for the identification of unmet needs for people with multiple sclerosis and their carers. Formal validation and reliability testing of the different language versions is recommended.

Europe↗
PubMed1983

Epidemiology of multiple sclerosis in U.S. veterans: 2. Latitude, climate and the risk of multiple sclerosis.

An analysis of ten climatic factors and elevation for the counties of birth of 4371 U.S. white male veterans with multiple sclerosis and matched controls has been made in relation to birthplace latitude. The climatic factors include an air pollution index, concentrations of minerals in ground water, measures of annual solar radiation, both in energy per unit area and in hours of sunshine, mean annual periods of high and low temperatures, and measures of annual rainfall and average humidity. These variables all significantly influence the risk of multiple sclerosis when analyzed alone, but when they are adjusted for latitude, their effect is found to be due to their correlation with this variable.

Air Pollution↗
PubMed1999

Magnetic resonance imaging results of the PRISMS trial: a randomized, double-blind, placebo-controlled study of interferon-beta1a in relapsing-remitting multiple sclerosis. Prevention of Relapses and Disability by Interferon-beta1a Subcutaneously in Multiple Sclerosis.

The PRISMS (Prevention of Relapses and Disability by Interferon-beta1a Subcutaneously in Multiple Sclerosis) trial was a double-blind, randomized, multicenter, phase III, placebo-controlled study of interferon-beta1a in 560 patients from 22 centers in 9 countries with clinically definite or laboratory-supported relapsing-remitting multiple sclerosis. The patients were randomized to receive recombinant interferon-beta1a (Rebif), 22 microg (6 mIU), 44 microg (12 mIU), or placebo, given subcutaneously, three times weekly for 2 years. All patients underwent biannual proton density/T2-weighted magnetic resonance imaging scans to determine the overall magnetic resonance imaging disease activity and burden of disease, and a cohort of 205 patients had 11 initial monthly proton density/T2-weighted and gadolinium-enhanced/T1-weighted magnetic resonance imaging scans. Over the 2 years, the placebo group showed a progressive median increase in burden of disease of 10.9%, whereas the 22-microg group and 44-microg group showed median decreases of 1.2% and 3.8%, respectively. The number of T2 active lesions and percentage of scans showing T2 activity on the biannual scans were also significantly reduced in both treatment groups compared with placebo, with a clear dose-effect favoring the 44-microg dose over the 22-microg dose. In the subgroup undergoing initial monthly scanning, this reduction in activity became statistically significant 2 months after the start of treatment. These results provide strong, objective evidence to support the positive clinical results of reduction in relapses and delay in disease progression. In addition, they also demonstrate a significant dosage effect, favoring the 44-microg dose.

Adult↗