Search PubMed⌕ Search

Biomedical subjects

M Clanet

Publications and source records attributed to M Clanet.

At least 37 records · Page 2Linked to original sources

[Imparting the diagnosis and educating patients with multiple sclerosis].

The neurologist must include the diagnosis announcement process in the comprehensive care of the MS patient. This process is standardized and adapted to the needs of each patient. It must integrate the pattern of psychological reactions following negative events and the adaptive strategies to a chronic disease. The announcement of the diagnosis, given by the neurologist, consists in technical information and emotional support, during a programmed discussion, at the adequate moment. The information must respond to the patient's needs, be easily understandable and given step by step according to the period of the disease. The neurologist is usually the first source of medical information followed by the MS societies and internet.

Adaptation, Psychological↗

[Hypothenar hammer syndrome].

The hypothenar hammer syndrome is an uncommon but underestimated lesion of the cubital artery caused by repetitive trauma at the level of the hamate bone. It characteristically occurs in patients with a history of manual work as metal workers, carpenters and motor mechanics. We present a case of a patient who developed this syndrome following intensive use of a dig. Clinical finding, diagnosis and treatment are discussed.

Aged↗

Cytokines in genetic susceptibility to multiple sclerosis: a candidate gene approach. French Multiple Sclerosis Genetics Group.

The immune system is involved in the pathophysiology of multiple sclerosis (MS) but the initiating antigen(s) is not yet identified. Since cytokines control both the intensity and the quality of the immune response they may be relevant candidates for the genetic susceptibility to MS. To analyze the contribution of type 1 and type 2 cytokine and cytokine receptor genes in the genetic susceptibility to MS, we have examined, in 116 French MS sibpairs, whether there is significant linkage between MS and 15 cytokine or cytokine receptor genes using 31 highly polymorphic genetic markers. The data were analyzed using the maximum likelihood score and the transmission disequilibrium approaches. None of the candidate genes tested was significantly linked to MS on the whole population. However, after stratification of the analysis on the basis of sharing (or not) of the HLA-DRB1*1501 allele, indication of linkage was found for the IL2-RB gene. These findings suggest that the IL2-RB locus contributes to the genetic susceptibility in a subgroup of MS patients.

Cytokines↗

Guidelines for autologous blood and marrow stem cell transplantation in multiple sclerosis: a consensus report written on behalf of the European Group for Blood and Marrow Transplantation and the European Charcot Foundation. BMT-MS Study Group.

Recent reports suggest the possible beneficial effects of haemopoietic stem cell transplantation (HSCT) in autoimmune diseases such as multiple sclerosis (MS). The definition of the risk/benefit ratio for such a treatment is perceived as a major issue for the neurological community worldwide. The First Consensus Conference on Bone Marrow Transplantation in Patients with Multiple Sclerosis was held in Milan, Italy on 21 February 1998. Participants from 16 European, North American, and South American countries discussed the guidelines for performing HSCT in MS. This conference was organized in order to: (a) define criteria for patient selection; (b) define transplantation procedures to maximize efficacy of the treatment and minimize its toxicity; (c) standardize patient outcome evaluation; and (d) establish an international working group to evaluate the efficacy and safety of HSCT in MS and to study the immunological changes related to HSCT in MS patients. During the meeting in Milan agreement was reached on: (a) the preparation and distribution of a consensus report on HSCT in MS and (b) the design of an open trial for an initial assessment of the safety and efficacy of HSCT in MS. The consensus reached during the meeting and the design of the clinical trial are summarized in this contribution.

Blood Transfusion, Autologous↗

No evidence for transmission disequilibrium between a new marker at the myelin basic protein locus and multiple sclerosis in French patients.

The myelin basic protein (MBP) gene is a candidate locus for susceptibility to multiple sclerosis. Several groups have tested a complex (TGGA)n repeat in the 5' region of this gene for association/linkage with multiple sclerosis, with divergent results. This region of tandem repetitive sequence has been subjected to complex rearrangements, and there is a possibility that alleles of the same size have different internal structures, which reduces the interest of this marker for linkage disequilibrium studies and may at least partly explain the conflicting results obtained so far. To overcome this problem, we isolated a new polymorphic (CA)n repeat within the Golli-MBP locus. The limited number of alleles identified makes this other marker suitable for transmission disequilibrium studies. We tested this marker for linkage with multiple sclerosis, using the transmission-disequilibrium test (TDT) on a sample of 196 nuclear families in which the genotypes of both parents could be unambiguously defined. We found no evidence of transmission disequilibrium between multiple sclerosis and any of the three alleles of this marker, even when the patients were subdivided according to their HLA-DRB1*1501 status. The present data thus provide no evidence for a contribution of the MBP gene to multiple sclerosis susceptibility in French patients.

Base Sequence↗

[Treatment of symptoms and relapses of multiple sclerosis].

Multiple sclerosis is a demyelinating disease of the central nervous system, with relapses. For more than 30 years steroids have been used in order to treat relapses. Available trials performed to determine which posology or administration route, and their efficacy, provided poor certitudes. Multiple sclerosis leads to symptoms that alter the quality of life. For fatigue, pain, spasticity and micturition disorder a treatment will be proposed.

Disease Progression↗

Involvement of de novo ceramide biosynthesis in lymphotoxin-induced oligodendrocyte death.

Both experimental and clinical studies suggest that lymphotoxin (LT) plays an important role in multiple sclerosis (MS) by inducing oligodendrocyte (OL) depletion. However, the mechanism of LT cytotoxicity is unknown. Because of the role of ceramide as a cell death mediator for a large variety of cytotoxic molecules, we have investigated the possible role of this second messenger in LT-induced cytotoxicity on SV40 immortalized new-born mice OL. Human recombinant LT exposure (50 ng/ml) resulted in intracellular ceramide accumulation which peaked at 48 h (approximately 170% increase) and paralleled LT-induced cytotoxicity. Moreover, fumonisin B1, a potent and specific ceramide synthase inhibitor, not only inhibited ceramide accumulation but also protected OL from LT cytotoxicity. These results suggest that LT-induced ceramide synthase stimulation and subsequent increased intracellular ceramide concentration are implicated in oligodendrocyte death.

Animals↗

Familial factors influence disability in MS multiplex families. French Multiple Sclerosis Genetics Group.

BACKGROUND: Both genetic and environmental factors play a role in the pathophysiology of MS and may influence the clinical expression of the disease. OBJECTIVE: To determine the contribution of familial factors to the clinical expression of MS. METHODS: The French Multiple Sclerosis Genetics Group identified 87 sibling pairs. For each patient, sex, age at onset, duration of the disease, and disease course from onset were recorded. Disability was determined by the progression index (PI), defined as the ratio of the Expanded Disability Status Scale (EDSS) score disease duration when the latter exceeded 5 years. Statistical analyses were performed either with a group of patients (clinical features, relation between human leukocyte antigen and clinical features) or with a group of sibpairs (concordance for clinical features). RESULTS: The mean age at onset was 29.6 years, the ratio of women to men was 59:28, and the mean PI was 0.27. There was no correlation for disease course and age at onset between sibs with MS. In contrast, we observed a weak but significant correlation of the PI in MS sibpairs (r = 0.234, p = 0.03). CONCLUSION: This study revealed a concordance in MS sibling pairs for the disease severity, supporting the hypothesis that the degree of disability might be partly influenced by familial factors (environmental or genetic).

Adult↗

A genome-wide search identifies two susceptibility loci for experimental autoimmune encephalomyelitis on rat chromosomes 4 and 10.

Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease of the central nervous system that exhibits many pathologic similarities with multiple sclerosis. The genetic loci that contribute to mononuclear cell infiltration of the central nervous system and clinical manifestations of EAE in the rat were investigated in the F2 progeny of the highly susceptible Lewis and resistant Brown Norway strains. The data confirmed that the Lewis allele of a MHC-linked gene is necessary, but not sufficient, to confer EAE susceptibility in the F2 progeny. Subsequent analyses were thus restricted to the subset of the F2 animals with EAE-predisposing MHC genotypes. A genome-wide scan approach was performed using 103 microsatellite markers covering 85% of the genome. Two non-MHC regions were identified, one near the centromere of chromosome 4 and the other on the long arm of chromosome 10, that significantly contributed to the disease. In addition, three regions on chromosomes 9, 13, and 17 were suggestive for linkage. Congenic mapping is now needed to reduce the support intervals encoding the loci of interest to sizes amenable to physical mapping and to eventually demonstrate the involvement of some of the candidate genes of immunologic importance localized in these regions.

Alleles↗

Chromosome 17q22-q24 and multiple sclerosis genetic susceptibility. American-French Multiple Sclerosis Genetic Group.

Recently, genome-wide searches for multiple sclerosis (MS) susceptibility genes have suggested that the chromosome 17q22-q24 region might contain susceptibility genes in two sets of families of different ethnic backgrounds (Finnish and British). Therefore, we decided to test this region in two sets of families of different ethnic backgrounds (American and French), but collected according to the same diagnostic criteria. All lod-score values were non-significant. Moreover, we could exclude that the 17q22-24 region might contain a gene increasing the sibling recurrence risk of MS over 1.4, rendering the existence of such a gene very unlikely, at least in the group of tested families.

Chromosome Mapping↗

Magnetic resonance imaging in multiple sclerosis.

Conventional magnetic resonance imaging (MRI) techniques acquire signal mainly from differences in relaxation properties and density of free water protons. Thus, the sensitivity in depicting lesions is high but pathological specificity is poor. Efforts are being made to increase the diagnostic power of MRI; better correlation with the clinical presentation and the use of better MRI criteria have increased the specificity of the conventional T2 sequences. New sequences, such as fast spin echo, turbo spin echo (TSE) or those derived from inversion recovery (fluid attenuated inversion recovery), have improved the detection of lesions. Acute phase monitoring focuses on changes in disease activity (new, recurring, enlarging, gadolinium-enhancing lesions) and chronic phase monitoring allows appreciation of the burden of the disease. However, MRI is considered as a secondary outcome measure in phase III trials because of insufficient correlation with the clinical disability. There is a continuing search for techniques that correlate better with clinical measures of the disease, such as the quantification of 'black holes' on T1-weighted images or the cerebral and spinal atrophy. The basic aspects of the pathological lesions in multiple sclerosis such as oedema, membrane disruption, demyelination, gliosis, cellular infiltration and axonal loss, can be studied more precisely by the new magnetic resonance techniques, which should better describe the actual clinical impact of the destructive process. In the past year the importance of axonal loss has simultaneously been confirmed by magnetic resonance spectroscopy and pathological findings. However, magnetization transfer imaging, magnetic resonance diffusion imaging and functional MRI are under intensive investigation for a better analysis of these different factors that impact on the reversibility of the patients disability.

Diffusion↗

A systematic study of oligodendrocyte growth factors as candidates for genetic susceptibility to MS. French Multiple Sclerosis Genetics Group.

OBJECTIVE: To test 23 genes coding for growth factors and their receptors as candidates for MS genetic susceptibility in 84 multiplex families of French origin by linkage analysis. BACKGROUND: Epidemiologic studies have indicated that genetic susceptibility in MS exists. To identify MS susceptibility genes, association and linkage studies were performed with candidate genes suggested by the pathology of MS. The most consistent result was genetic association and linkage of MS to human leukocyte antigen (HLA) DR15. Recent advances in the knowledge of MS pathology have suggested that the oligodendrocyte, the myelin-forming cell in the CNS, and its growth factors might play a crucial role in MS. METHODS: Fifty-two polymorphic markers within or flanking 23 candidate genes were used. Data were analyzed with the maximum likelihood score (MLS) approach. We also searched for a genetic interaction with HLA. RESULTS: Negative results were obtained for all candidate genes. The lower limits of the relative risk (Xs) possibly excluded for any candidate gene ranged from 1.3 to 2.8. Positive MLS values (up to 0.93) were observed for transforming growth factor beta 3 (TGFbeta3) in HLA DR15-associated families, suggesting a possible role for this growth factor in interaction with HLA. CONCLUSIONS: Oligodendrocyte growth factors do not play a significant role in MS genetic susceptibility, at least in the tested sample. TGFbeta3, the only gene highlighted by this study, deserves further analysis.

Adult↗

[MRI visualization of multiple sclerosis lesions].

Magnetic resonance imaging represents voxels (volume elements) of the body placed in a magnet, by their magnetization determined under various acquisition conditions weighting the contrast of the image by the density of free water protons and their relaxation times T1 and T2. Thus, the sensitivity in depicting lesions is high but pathological specificity is poor. Efforts are made to increase the diagnosis powerfulness of M.R.I. in multiple sclerosis: a careful correlation with the clinical presentation and the use of better M.R.I. criteria increase the specificity of the conventional T2 sequences. New sequences such as fast spin echo (F.S.E.), turbo spin echo (T.S.E.) or derived from inversion recovery (F.L.A.I.R.: fluid attenuated inversion recovery) improve the detection of lesions. Under specific conditions M.R.I. can be used to monitor the evolution of M.S. Acute phase monitoring focuses on changes in disease activity, new, recurring, enlarging, gadolinium (Gd) enhancing lesions, and chronic phase monitoring appreciate the burden of the disease. However M.R.I. is always considered as a secondary outcome in the phase III trials because insufficient correlations with the clinical disability. In the neurological daily practice conventional M.R.I. is of poor interest in the follow up of individual M.S. patients considering the weakness of prognosis value and the problems in the measurement of the lesions load which is emphasized in the methodology of the clinical trials. Nevertheless, there is a continuing search for techniques which correlate better with clinical measures of the disease such as the quantification of "black holes" on T1 w images or the cerebral and spinal atrophy. New techniques allow to weight the signal by the movement (diffusion imaging), by the complexity of the molecular architecture (magnetization transfer imaging), by the chemical shift (chemical shift imaging) or by the local status of oxygenation (functional M.R.I.). The basic aspects of the pathological lesions in M.S., edema, membrane disruption, demyelination, gliosis, cellular infiltration and axonal loss can be studied more precisely by these new M.R. techniques which should better describe the actual clinical impact of the destructive process. In the last year the importance of axonal loss has simultaneously been confirmed by M. R. spectroscopy and pathological findings. However, magnetization transfer imaging, M.R. diffusion imaging and functional M.R.I. are intensively under investigation for a better analysis of these different factors conditioning the reversibility of the patient disability.

Contrast Media↗