Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “SCLEROSIS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed1978

[Thymus-dependent lymphocytes in multiple sclerosis and amyotrophic lateral sclerosis].

A study of the rosetteforming possibilities of T-lymphocytes in the peripheral blood of patients with disseminated sclerosis and lateral amyotrophical sclerosis detected a significant deficit of a subpopulation of T-cells, which form the most active rosettes of the morula type. Besides, in patients with disseminated sclerosis the relative amount of rosetteforming lymphocytes in the peripheral blood is significantly lower.

Adolescent↗
PubMed1998

Magnetic resonance studies of intramuscular interferon beta-1a for relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group.

The Multiple Sclerosis Collaborative Research Group trial was a double-blind, randomized, multicenter, phase III, placebo-controlled study of interferon beta-1a (IFNbeta-1a; AVONEX) in relapsing forms of multiple sclerosis. Initial magnetic resonance imaging results have been published; this report provides additional results. Treatment with IFNbeta-1a, 30 microg once weekly by intramuscular injection, resulted in a significant decrease in the number of new, enlarging, and new plus enlarging T2 lesions over 2 years. The median increase in T2 lesion volume in placebo and IFNbeta-1a patients was 455 and 152 mm3, respectively, at 1 year and 1,410 and 628 mm3 at 2 years, although the treatment group differences did not reach statistical significance. For active patients, defined as those with gadolinium enhancement at baseline, the median change in T2 lesion volume in placebo and IFNbeta-1a patients was 1,578 and -12 mm3 and 2,980 and 1,285 mm3 at 1 and 2 years, respectively. Except for a minimal correlation of 0.30 between relapse rate and the number of gadolinium-enhanced lesions, correlations between MR and clinical measures at baseline and throughout the study were in general poor. Once weekly intramuscular IFNbeta-1a appears to impede the development of multiple sclerosis lesions at an early stage and has a favorable impact on the long-term sequelae of these inflammatory events as indicated by the slowed accumulation of T2 lesions.

Brain↗
PubMed1978

Electroencephalographic studies in multiple sclerosis. Specific changes in benign multiple sclerosis.

EEG changes were analysed in a group of 260 patients with definite multiple sclerosis, 156 women and 104 men, average age 38.8, at different stages of the disease. Among 103 patients with an evolution up to 5 years, 34% had significantly abnormal EEG'S while in 157 patients with an evolution from 5 to 45 years abnormal records were obtained in 47.8%. The larger group showed EEG differences between benign (66 patients), malignant (23 patients) and moderate courses (68 patients) patients. The frequency of abnormal and doubtful EEGs was highest in the benign group (80.4%) and largest in the malignant group (24.1%). The main characteristic in malignant multiple sclerosis in the steadily progressive stage was a flat EEG. There was also a significant correlation between a flat EEG and intellectual deficit. In benign multiple sclerosis the dominant activities were slow (6-10 c/sec) and high voltage (80-180 muV) alpha-theta rhythms spreading all over the cortex, usually associated with "centrencephalic" discharges. A self-limiting effect of lesions around the 3rd ventricle on auto-agressive immunological processes is proposed.

Adult↗
PubMed2006

The development and validation of the impact of multiple sclerosis scale and the symptoms of multiple sclerosis scale.

OBJECTIVE: To develop and validate the Impact of Multiple Sclerosis Scale (IMSS) and the Symptoms of Multiple Sclerosis Scale (SMSS) using the Extended Disability Status Scale (EDSS) for construct validity. DESIGN: Panel design involving test-retest over 4 months. SETTING: A mailed survey. PARTICIPANTS: Volunteers with a diagnosis of multiple sclerosis (MS) recruited from an MS support service in Australia: 193 people (mean age, 39y) and 150 people participated at time 1 and time 2, respectively. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Principal components analyses, the Cronbach alpha, and descriptive statistics for the 2 scales; correlations for construct validity with the EDSS and retest; and confirmatory factor analysis to test the stability of IMSS and SMSS components over time. RESULTS: The IMSS yielded 5 independent and reliable components; the SMSS yielded 3 components; both component structures were stable over time. These scales showed convergent validity with the EDSS. CONCLUSIONS: The IMSS and SMSS are psychometrically sound scales suitable for clinical and research purposes to assess the symptoms and impact of MS.

Adult↗
PubMed1997

Randomised placebo-controlled trial of monthly intravenous immunoglobulin therapy in relapsing-remitting multiple sclerosis. Austrian Immunoglobulin in Multiple Sclerosis Study Group.

BACKGROUND: Multiple sclerosis is an autoimmune disorder characterised by the repeated occurrence of demyelinating lesions within the central nervous system. Uncontrolled studies and experimental evidence suggest beneficial effects of repeated administration of intravenous immunoglobulin (IVIg) by immunomodulating mechanisms and induction or remyelination. We aimed to investigate the efficacy of IVIg in a randomised double-blind multicentre study. METHODS: Patients with relapsing-remitting multiple sclerosis were randomly assigned a monthly dose of IVIg (0.15-0.2 g/kg bodyweight) or placebo. Duration of treatment was 2 years. The primary outcome measures were the effect of treatment on clinical disability-measured by the absolute change in Kurtzke's expanded disability status scale (EDSS) score- and the proportion of patients with improved, stable, or worse clinical disability (> or = 1.0 grade on EDSS score). FINDINGS: Of the 243 patients screened, 150 met our eligibility criteria and were randomly assigned to IVIg or placebo. Before the start of treatment two patients in the placebo group dropped out, so there were 75 patients in the IVIg group and 73 in the placebo group. Intention-to-treat analysis showed that IVIg treatment had a beneficial effect on the course of clinical disability. The EDSS score decreased in the IVIg-treated patients and increased in the placebo group (-0.23 [95% CI -0.43 to -0.03] vs 0.12 [-0.13 to 0.37], p = 0.008). In the IVIg group, the numbers of patients with improved, stable, or worse clinical disability were 23 (31%), 40 (53%), and 12 (16%) compared with ten (14%), 46 (63%), and 17 (23%) in the placebo group. Side-effects were reported in three (4%) IVIg-treated patients and in four (5%) placebo-group patients, but were not directly linked to study medication. INTERPRETATION: Monthly IVIg is an effective and well-tolerated treatment for patients with relapsing-remitting multiple sclerosis.

Adult↗
PubMed2000

The effect of interferon beta-1b treatment on MRI measures of cerebral atrophy in secondary progressive multiple sclerosis. European Study Group on Interferon beta-1b in secondary progressive multiple sclerosis.

The recently completed European trial of interferon beta-1b (IFNbeta-1b) in patients with secondary progressive multiple sclerosis (SP multiple sclerosis) has given an opportunity to assess the impact of treatment on cerebral atrophy using serial MRI. Unenhanced T(1)-weighted brain imaging was acquired in a subgroup of 95 patients from five of the European centres; imaging was performed at 6-month intervals from month 0 to month 36. A blinded observer measured cerebral volume on four contiguous 5 mm cerebral hemisphere slices at each time point, using an algorithm with a high level of reproducibility and automation. There was a significant and progressive reduction in cerebral volume in both placebo and treated groups, with a mean reduction of 3.9 and 2.9%, respectively, by month 36 (P = 0.34 between groups). Exploratory subgroup analyses indicated that patients without gadolinium (Gd) enhancement at the baseline had a greater reduction of cerebral volume in the placebo group (mean reduction at month 36: placebo 5.1%, IFNbeta-1b 1.8%, P < 0.05) whereas those with Gd-enhancing lesions showed a trend to greater reduction of cerebral volume if the patient was on IFNbeta-1b (placebo 2.6%, IFNbeta-1b 3.7%; P > 0.05). These results are consistent with ongoing tissue loss in both arms of this study of secondary progressive multiple sclerosis. This finding is concordant with previous observations that disease progression, although delayed, is not halted by IFNbeta. The different pattern seen in patients with and without baseline gadolinium enhancement suggests that part of the cerebral volume reduction observed in IFNbeta-treated patients may be due to the anti-inflammatory/antioedematous effect of the drug. Longer periods of observation and larger groups of patients may be needed to detect the effects of treatment on cerebral atrophy in this population of patients with advanced disease.

Adult↗
PubMed1995

Significant correlation between connective tissue growth factor gene expression and skin sclerosis in tissue sections from patients with systemic sclerosis.

The role of some growth factors and cytokines in the pathogenesis of systemic sclerosis (SSc) has been suggested. In particular, the contribution of transforming growth factor beta in the progression of skin sclerosis is suspected. Connective tissue growth factor (CTGF) was originally identified in human umbilical vein endothelial cells, and a recent study has revealed that human skin fibroblasts produce CTGF after stimulation with transforming growth factor beta. In the present study, the distribution of CTGF gene expression in tissue sections from patients with SSc was investigated by digoxigenin-labeled in situ hybridization. Strong CTGF mRNA signals were observed in the fibroblasts in sclerotic lesions, especially in the deep dermis, of the skin specimens from patients with SSc, whereas there was no expression in the skin from normal controls. The number of fibroblasts with positive hybridization signals was more abundant in the dermis from the sclerotic stage than in that from the inflammatory stage. Our findings indicate a correlation between CTGF gene expression and skin sclerosis and support the hypothesis that transforming growth factor-beta plays an important role in the pathogenesis of SSc, because transforming growth factor beta is the only inducer for CTGF identified to date.

Adolescent↗
PubMed1977

Aberrant CSF protein fractions found by electrofocusing in multiple sclerosis. A study of 26 cases with clinically verified or probable multiple sclerosis and 2 cases with optic neuritis.

The CSF gamma-globulin patterns found by electrofocusing in multiple sclerosis can be classified into five (a-e) mean patterns, where the individual bands lie very close together. However, in some patients with verified or probable multiple sclerosis conspicuous bands are found. The electrofocusing patterns from 28 such cases were compared with those reported by Kjellin and Vesterberg and with 20 cases of verified multiple sclerosis collected by chance. Differences were found with regard to the frequency of the different mean patterns, the occurrence of a double fraction in region '5', a single fraction in region '7' and a highly alkaline fraction. The electrofocusing findings have been compared with the clinical data of the 28 patients. There seems to be some correlation between the patterns of conspicuous bands and the duration and course of the disorder as well as probable sites of the CNS lesions. No indication was found, that either a high CSF gamma-globulin value and/or in a high degree of barrier damage was a prerequisite for the occurrence of conspicuous bands in the CSF gamma-globulin region. The aberrant electrofocusing patterns might be genetically determined or caused by some unusual agents (possible viral) or autoimmune reactions, modified by other than gentically divergent factors.

Cerebrospinal Fluid Proteins↗
PubMed2000

Sustained clinical benefits of glatiramer acetate in relapsing multiple sclerosis patients observed for 6 years. Copolymer 1 Multiple Sclerosis Study Group.

In a randomized, placebo-controlled, double-blind study, glatiramer acetate (Copaxone) reduced the relapse rate and slowed accumulation of disability for patients with relapsing - remitting multiple sclerosis. Of the original 251 patients randomized to receive glatiramer acetate or placebo, 208 chose to continue in an open-label study with all patients receiving active drug. The majority of the original double-blind cohort continues to receive glatiramer acetate by daily subcutaneous injection and are evaluated at 6-month intervals and during suspected relapse. The data reported here are from approximately 6 years of organized evaluation, including the double-blind phase of up to 35 months and the open-label phase of over 36 months. Daily subcutaneous injections of 20 mg glatiramer acetate were well tolerated. The mean annual relapse rate of the patients who received glatiramer acetate since randomization and continued into the open-label study was 0.42 (95% confidence interval (CI), CI=0.34 - 0.51). The rate per year has continued to drop and for the sixth year is 0.23. Of the group who have received glatiramer acetate without interruption for 5 or more years, 69.3% were neurologically unchanged or have improved from baseline by at least one step on the Expanded Disability Status Scale (EDSS). Patients who left the open-label phase were surveyed by questionnaire. The majority responded, providing information about their current status and reasons for dropping out. This study demonstrates the sustained efficacy of glatiramer acetate in reducing the relapse rate and in slowing the accumulation of disability in patients with relapsing forms of multiple sclerosis. Multiple Sclerosis (2000) 6 255 - 266

Adjuvants, Immunologic↗
PubMed2001

Disease specific quality of life instruments in multiple sclerosis: validation of the Hamburg Quality of Life Questionnaire in Multiple Sclerosis (HAQUAMS).

Quality of life (QoL) is discussed as an additional outcome measure in multiple sclerosis (MS). However, few questionnaires assessing disease specific QoL in MS have been published. On the basis of the literature and interviews with clinicians and MS patients, we have developed a disease specific QoL instrument and validated it in a broad range of patients with MS. In this study, a heterogeneous sample of n = 237 MS patients completed the newly developed Hamburg Quality of Life Questionnaire in Multiple Sclerosis (HAQUAMS, in German language) and a battery of already validated questionnaires. They further underwent neurological scoring and objective tests. By these means, we investigated its validity, appropriateness, internal consistency, and retest reliability. Internal consistency and retest coefficients were high and satisfied psychometric standards. Convergent and discriminant validity was supported by direction, magnitude and pattern of correlations with other health measures. HAQUAMS subscales and its total score distinguished between patient groups of varied disease severity, cognitive impairment, and affective symptomatology. No floor or ceiling effects were found in either of the HAQUAMS subscales. The HAQUAMS is a reliable, valid and appropriate instrument for QoL assessment in multiple sclerosis. Data of responsiveness are currently being obtained.

Adult↗
PubMed1976

[The pathogenesis of multiple sclerosis. Cytotoxic antibodies against myelin sheath tissue in multiple sclerosis].

Cytotoxic antibodies to myelin can be demonstrated by the method of 51Cr-release from chick erythrocytes coated with myelin basic protein. The cytotoxic antibody is inactivated by heating to 56 degrees C and needs complement in order to exert its action. The antibody was determined as IgM and IgG. It has relative specifity and shows cross-reaction with other basic proteins. The cytotoxic antibody was found in only 8% of healthy persons. Patients with multiple sclerosis were positive in 87% of the cases and in acute cases in 94%. In other neurological diseases cytotoxic antibody was present in 64%. The occurrence of cytotoxic antibody to myelin protein is not specific for a particular neurological disorder, especially not for multiple sclerosis. Cytotoxic antibodies arise as a secondary phenomenon, they are not the cause of the disease involved. They appear to be suitable, however, to determine, in association with cellular immunological reactions against myelin which may be regarded as the "primary" immunological processes, the demyelination process in the multiple sclerosis focus.

Antibody Specificity↗
PubMed2003

Primary lateral sclerosis: a rare upper-motor-predominant form of amyotrophic lateral sclerosis often accompanied by frontotemporal lobar degeneration with ubiquitinated neuronal inclusions? Report of an autopsy case and a review of the literature.

We report the autopsy findings of an 82-year-old woman who exhibited slowly progressive upper motor neuron signs (pseudobulbar palsy, muscle weakness and positive Babinski's sign) in the absence of lower motor neuron signs, which were followed by progressive dementia and frontotemporal atrophy, and who died 7 years and 4 months after onset of the disease. In this patient, the upper motor neuron system, including the precentral cortex and descending pyramidal tract, was severely degenerated, but the lower motor neurons and innervated skeletal muscles were well preserved. A few lower motor neurons were found to contain cytoplasmic inclusion bodies characteristic of amyotrophic lateral sclerosis (i.e., Bunina bodies and ubiquitin-positive skeins). However, fragmentation of the Golgi apparatus was not evident in the anterior horn cells examined. Therefore, it was considered that the lower motor neurons were also involved, but that the rate of degeneration of these neurons was very slow in the disease process. Marked frontotemporal lobar degeneration characterized by microvacuolation, and ubiquitin-positive neuronal inclusions and dystrophic neurites in cortical layer II were also observed, the precentral cortex being the most severely affected area. Similar ubiquitin-positive structures were also observed in the neostriatum. Finally, a survey of the literature based on this patient's clinical and pathological features led us to conclude that the rare clinical syndrome of primary lateral sclerosis is, in general, a rare upper-motor-predominant form of amyotrophic lateral sclerosis that is often accompanied by frontotemporal lobar degeneration with ubiquitinated neuronal inclusions.

Aged↗
PubMed1987

Renal disease in pregnancy. Three controversial areas: mesangial IgA nephropathy, focal glomerular sclerosis (focal and segmental hyalinosis and sclerosis), and reflux nephropathy.

Whether gestation has adverse effects on the course of renal disease is controversial. Three diseases regarding which conflicting opinions are especially noteworthy are IgA nephropathy, focal and segmental hyalinosis and sclerosis, and reflux nephropathy. We analyzed 102 pregnancies in 65 women with IgA nephropathy, noting hypertension in 63% of the gestations (severe in 18%), decreases in renal function in 22%, and biopsy evidence demonstrating a significantly greater amount of glomerular proliferation and crescents as well as focal and segmental hyalinosis and sclerosis when the renal histology from women who were pregnant and those who had never conceived were compared. Our experience with glomerular sclerosis is limited to 28 gestations in 15 patients, but the clinical findings resemble those of women with IgA nephropathy who conceived. Finally, we analyzed 227 pregnancies in 95 women with normal renal function and reflux nephropathy comparing results to 118 gestations in 42 patients with evidence of dysfunction (serum creatinine SCr greater than 1.25 mg/dL). Women with preserved function had good outcomes in general, whereas hypertension (36%) and an accelerated decline in function (8%) were observed in the groups that had moderate renal insufficiency in the initial stage of pregnancy. Increased proteinuria was the best predictor of progression of reflux nephropathy in both groups.

Biopsy↗
PubMed1989

Determination of an epitope of the diffuse systemic sclerosis marker antigen DNA topoisomerase I: sequence similarity with retroviral p30gag protein suggests a possible cause for autoimmunity in systemic sclerosis.

The possibility that viruses play a role in the etiology of various autoimmune diseases has been proposed. One approach to the search for these agents involves identifying potential crossreactive epitopes in viruses that infect cells of the immune system or of the target tissues. Antibodies to DNA topoisomerase I are the marker autoantibodies for diffuse systemic sclerosis. The major epitope of the antigen was therefore sought through cloning and sequencing of the cDNA for human topoisomerase I and eventually by the synthesis of the smallest possible peptide recognized by sera from patients with the diffuse form of systemic sclerosis. The antigenic 11-amino acid sequence contains 6 sequential amino acids that are identical to a sequence present in the group-specific antigen (p30gag) of some mammalian retroviruses. This sequence is separated by only 1 amino acid from the retroviral epitope sequence that crossreacts with autoantibodies against the marker antigen for mixed connective-tissue disease and systemic lupus erythematosus, the 70-kDa polypeptide of U1 ribonucleoprotein particles. These findings suggest that a retroviral agent may be involved in the pathogenesis of systemic sclerosis and other connective tissue diseases and that antibodies to intracellular antigens are not involved in the pathogenesis of autoimmune disease but may be useful as footprints for tracking the potential etiological agent of autoimmune disease.

Amino Acid Sequence↗
PubMed2006

Neuroaxial anesthesia in a patient with progressive systemic sclerosis : case presentation and review of the literature on systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc), a progressive disease characterized by excessive accumulation of connective tissue components. Although most patients have long survival, some of them progress rapidly to death. Pulmonary system involvement and pulmonary hypertension are the most frequent cause of death. When the patient with SSc is to be operated, the anesthetic procedure could be a serious problem. In this article, we report a combined spinal--epidural technique in a patient with progressive SSc and the anesthetic considerations that could be recommended for these patients. CASE PRESENTATION: A 68-year-old woman who had a history of progressive systemic sclerosis, pulmonary fibrosis, kyphoscoliosis and decreased oral apertura underwent total hip arthroplasty. This operation was performed successfully under combined spinal epidural anesthesia. CONCLUSION: Systemic sclerosis is a complex disease that involves multiple organ systems. Every aspects of anesthetic care may be altered or hindered by the pathogenesis of disease. Although the choice of regional or general anesthesia is unclear, to choose combined spinal epidural anesthesia may be useful.

Journal Article↗
PubMedDate not supplied

Clinical evaluation of systemic sclerosis: a comprehensive panel of diagnostic tests to assess skin, microvascular and visceral involvement. The Genoese Group for the Study of Systemic Sclerosis.

The work proposes a set of diagnostic tests and relative clinical scores for the staging and follow-up of patients with systemic sclerosis. Thirty-one consecutive patients (30 females, 1 male, age range 17-65 years) affected by systemic sclerosis, according to the American College of Rheumatology criteria for classification of this disease, were enrolled in the study at the time of their first admission to the Department of Internal Medicine in Genoa. The following battery of tests was utilized: nailfold capillary videomicroscopy, esophageal manometry and pH-metry, lung vital capacity and diffusing capacity for carbon monoxide, intrarenal duplex Doppler sonography, echocardiography and skin plicometry. Good compliance by the patients was obtained for the tests we used. We found that nailfold capillary videomicroscopy and plicometry scores were statistically associated each other as well as with the scores measuring esophagus and/or lung function. The use of wide range of diagnostic procedures, such as those proposed in this paper, allows appropriate definition of the stage of patients with systemic sclerosis. The use of nailfold capillaroscopy and skin plicometry as the simplest tests for monitoring patients is suggested: the scores derived from these procedures are statistically associated with some internal organ status and could be useful in the evaluation of therapeutical results.

Adolescent↗
PubMed2006

Longitudinal analysis of serum cytokine concentrations in systemic sclerosis: association of interleukin 12 elevation with spontaneous regression of skin sclerosis.

OBJECTIVE: Skin sclerosis that progresses in the earlier disease phase in systemic sclerosis (SSc) spontaneously regresses thereafter. We investigated the relationship between changes of the serum cytokine profile and changes in skin fibrosis in patients with SSc. METHODS: Serum cytokine levels were examined by ELISA using 180 sera samples from 26 patients with early diffuse cutaneous SSc (dcSSc) with mean disease duration of 2.1 years. The mean followup period was 4.9 years (range 2-8). Cytokine mRNA expression in the affected skin was quantified by real-time reverse transcription-polymerase chain reaction. RESULTS: Modified Rodnan total skin thickness score decreased after 2, 4, and 6 years compared to that at first visit. Serum levels of the Th2 cytokines interleukin 6 (IL-6) and IL-10 and monocyte chemotactic protein-1 (MCP-1) were higher at first evaluation compared to healthy controls, while IL-4 levels were normal. Levels of all Th2 cytokines generally decreased as skin sclerosis regressed. Conversely, levels of serum IL-12, a Th1-inducing cytokine, were lower at first visit relative to controls, but increased by roughly 15-fold after 6 years to significantly higher levels than controls. Surviving dcSSc patients exhibited elevated IL-12 levels compared to deceased patients. Serum levels of transforming growth factor-ss1 (TGF-ss1), a fibrogenic cytokine, increased throughout followup, with slightly decreased levels at later timepoints. IL-12 mRNA expression was upregulated in affected skin from patients with late-stage dcSSc, while TGF-ss1 and MCP-1 expression was downregulated. CONCLUSION: These results suggest that a shift from Th2 to Th1 response correlates with improvement in skin fibrosis in SSc, and that IL-12 level is a serologically useful marker for disease activity and prognosis.

Adult↗