Biomedical subjects

Gilles Edan

Publications and source records attributed to Gilles Edan.

17 recordsLinked to original sources

PubMed2006

Neutralizing antibodies to interferon beta in multiple sclerosis: analytical evaluation for validation of a cytopathic effect assay.

BACKGROUND: Recent guidelines have recommended the use of validated assays for the measurement of neutralizing antibodies (NABs) to interferon beta (IFNbeta) in patients with multiple sclerosis (MS). In an attempt of validation, we studied the analytical performance of a bioassay based on antiviral cytopathic effect (CPE) using WISH cells and the vesicular stomatitis virus (WISH/VSV CPE). METHODS: NAB titres measured with the WISH/VSV CPE assay in 63 sera from IFNbeta-treated MS patients were compared to those obtained with the reference CPE method using A549 cells and the encephalomyocarditis virus. Binding antibodies (BABs) were measured using a capture ELISA as a screening test for NABs. RESULTS: No false-negative BAB was obtained in our patients. The between-run coefficients of variation (CVs) determined with log10 titres of the NIH anti-IFNbeta (G038-501-572) yielded good results (<or=10.4%) and within-run variability was excellent (CV<or=2%). The log10 titres obtained with both CPE assays were highly correlated (r=0.969 and r=0.884 for anti-IFNbeta-1a and anti-IFNbeta-1b, respectively). The same patients were found NAB-positive with both CPE assays. CONCLUSION: Because of its good precision, sensitivity and excellent correlation with the reference CPE method, the WISH/VSV CPE bioassay can be used in the follow-up of IFNbeta-treated MS patients.

Adult↗

PubMed2006

Linkage disequilibrium screening for multiple sclerosis implicates JAG1 and POU2AF1 as susceptibility genes in Europeans.

By combining all the data available from the Genetic Analysis of Multiple sclerosis in EuropeanS (GAMES) project, we have been able to identify 17 microsatellite markers showing consistent evidence for apparent association. As might be expected five of these markers map within the Major Histocompatibility Complex (MHC) and are in LD with HLA-DRB1. Individual genotyping of the 12 non-MHC markers confirmed association for three of them--D11S1986, D19S552 and D20S894. Association mapping across the candidate genes implicated by these markers in 937 UK trio families revealed modestly associated haplotypes in JAG1 (p=0.019) on chromosome 20p12.2 and POU2AF1 (p=0.003) on chromosome 11q23.1.

Calcium-Binding Proteins↗

PubMed2006

[Drug therapy in multiple sclerosis].

For the last 10 years, three disease-modifying-therapy drugs have been approved by the French health authorities for the treatment of relapsing-remitting MS: two of them are immunomodulatory agents (interferon beta 1a or 1b and glatiramer acetate), administered by subcutaneous or intramuscular injections at different time points, reducing by about 30% the risk of relapses. The third drug approved is an immunosuppressive agent, mitoxantrone, administered intravenously at a dose of 12 mg/m2 per month up to a maximum cumulative dose of 72 mg/m2, used as a second line therapy in rapidly worsening relapsing MS non responder to immunomodulatory agents. The impact of such medications in MS patients with gradual progression of disability has not yet been established either in secondary or primary progressive MS.

Adjuvants, Immunologic↗

PubMed2006

Assessment of cognitive dysfunction in multiple sclerosis.

Cognitive deficit can be an early feature in the course of multiple sclerosis, may occur clinically isolated, impacts on social activities and could reflect disease progression that is independent of physical disability with potential therapeutical consequences. Neuropsychological tests should be independent of motor coordination or visuo-spatial ability, but sensitive to subtle cognitive changes, exploring attention speed and working memory They could be included in brief batteries with good normative data and alternative forms for future therapeutic trials. We recommend for a brief battery of neuropsychological tests the inclusion of PASAT and two memory tests: the learning stage of CVLT and backward Digit Span with a total time duration of 30 min. A complementary tool could be a cognitive questionnaire for informant. After a relapse, cognitive assessment should be performed at least 8 weeks afterwards. If the patient presents with psychiatric symptoms, a specific assessment should be proposed before starting a complete cognitive assessment. Finally, we propose some red flags warranting neuropsychological screening: patients with a mild physical disability, but unable to maintain their professional activities, pathological laughing-crying, increased age and low educational level.

Cognition Disorders↗

PubMed2006

A model for a regional health information network sharing clinical information between professionals in Britanny.

The purpose of this paper is to present a generic model of information system supporting healthcare networks for health professionals in Brittany. This model is aimed to develop cooperation between hospital professionals, primary care and practitioners whatever the specific pathology, by providing tools for exchanging and sharing medical-related data. The model is designed based on the heterogeneity factors revealed by a prospective survey. It includes secured exchange of nominative medical data, all other information and activities being accessible by a Web portal. Other associated tools are a synchronous collaborative platform, and a e-learning module. The first implementation, currently in use by the professionals, is presented for the existing neurology healthcare networks.

France↗

PubMed2005

Effects of pregnancy and child birth on urinary symptoms and urodynamics in women with multiple sclerosis.

OBJECTIVE: Our objective was to study the impact of pregnancy and delivery on vesicourethral disorders in patients with multiple sclerosis (MS). DESIGN AND SETTING: We performed a retrospective chart review of records of women diagnosed with MS who were referred to the clinic. PARTICIPANTS: A total of 102 women with MS (mean age of 44.7 +/- 11.4 years at the time of the study and mean age of 30.0 +/- 9.6 years at the onset of MS) participated in the study. The mean duration of disease was 15 +/- 10 years. The mean Expanded Disability Status Scale score was 5.4 +/- 1.8. MAIN OUTCOME MEASURES: For each patient, demographic data, disease characteristics, urological and obstetrical history and urodynamic data were collected. Urinary disorders were classified as irritative (urinary urgency and frequency) or as obstructive (hesitancy of micturition, reduced or interrupted urinary stream and sensation of incomplete bladder emptying). Urodynamic study consisted of cystometry with continuous recording of urethral sphincter electromyography in 77 (76%) cases. Intravesical and intraurethral pressures were recorded. Bladder dysfunctions were classified into neurogenic detrusor overactivity or detrusor underactivity. RESULTS: Pregnancies and deliveries did not influence symptoms. Moreover, the only statistical difference from a urodynamic point of view was a decrease in maximal urethral closure pressure. CONCLUSION: No interaction between pregnancy, delivery and urinary symptoms was found in this study. The effects of pregnancy and delivery seemed to be the same in women with MS and in healthy women, with a tendency towards a decrease in urethral pressure in women with MS.

Adult↗

PubMed2005

Only physical aspects of quality of life are significantly improved by bilateral subthalamic stimulation in Parkinson's disease.

BACKGROUND: The well known global improvement of quality of life (QoL) after bilateral high frequency chronic deep brain stimulation of the subthalamic nucleus (STN DBS) in Parkinson's disease (PD) is in contrast to behavioral disturbances as observed after surgery. Indeed the impact of DBS on physical versus mental aspects of QoL in PD remains unknown. OBJECTIVE: To assess the influence of bilateral STN DBS on physical versus mental aspects of QoL in Parkinson's disease. METHODS: The results of 27 patients for the Unified Parkinson's disease Rating Scale (UPDRS), Parkinson's Disease Questionnaire 39 (PDQ39) and Short Form 36 health survey questionnaire (SF36) were compared before surgery and after 12 months of bilateral STN DBS. RESULTS: Comparing off-dopa conditions before versus 12 months after surgery, both UPDRS part II and part III significantly improved: 32.6% and 52%, respectively. UPDRS part I scores did not change significantly at 12 months. As for PDQ39, the global score significantly improved after surgery (21.1 %) as did four subscores: mobility (25.6 %), activity of daily living (34.5 %), stigma (40.1 %) and bodily discomfort (30 %). Three PDQ39 subscores, however, showed no significant changes: emotional well-being (10.7 %), social support (3.2%) and cognition (8.5 %) and one item even worsened: communication (-7.7 %). In SF36, only physical items significantly improved. CONCLUSION: Using clinician's based rating scale, bilateral STN DBS showed significant improvement in PD patients at 12 month follow up. However, using patient's self-assessment scales, the clinical benefit of STN DBS was more subtle: physical items of QoL significantly improved, whereas mental items such as emotional well-being, social support, cognition and communication showed no improvement. Our results are suggestive of a dissociation of motor and non-motor symptoms control after bilateral STN DBS in PD patients.

Adult↗

PubMed2005

Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria".

New diagnostic criteria for multiple sclerosis integrating magnetic resonance image assessment with clinical and other paraclinical methods were introduced in 2001. The "McDonald Criteria" have been extensively assessed and used since 2001. New evidence and consensus now strengthen the role of these criteria in the multiple sclerosis diagnostic workup to demonstrate dissemination of lesions in time, to clarify the use of spinal cord lesions, and to simplify diagnosis of primary progressive disease. The 2005 Revisions to the McDonald Diagnostic Criteria for MS should simplify and speed diagnosis, whereas maintaining adequate sensitivity and specificity.

Humans↗

PubMed2004

Rationale for the use of mitoxantrone in multiple sclerosis.

Mitoxantrone is a member of the anthracendione family developed to treat malignancies and increasingly used to treat multiple sclerosis (MS). It has been studied as a treatment for MS since the late 1980s, and is licensed in a number of countries for progressive and worsening MS. Review of the published earlier open-label, and more recently of controlled trials suggests that mitoxantrone is efficacious in cases of worsening MS that have an inflammatory component as evidenced by progression with or without superimposed relapses and/or gadolinium (Gd) enhancing magnetic resonance (MR) lesions. Today there is no robust evidence of efficacy in primary progressive MS or in later stages of secondary progressive MS beyond an EDSS score of 6. Relevant immunomodulatory mechanisms act both on T- and B-cell function, and mitoxantrone has selective immune effects in MS by decreasing levels of TNF-alpha, IL-2, IL-2R-beta1, IL-10 and IFN-gamma. Adverse events include nausea, alopecia, infections, menstrual disorders, risk of cardiotoxicity and malignancy. Different regimens are used according to different regulatory demands in different countries. The two most commonly used regimens are every 3 months intravenous (i.v.) 12 mg/m2 for 2 years or 20 mg mitoxantrone (i.v.) combined with 1 g methylprednisolone (i.v.) every 4 weeks for 6 months. The cumulative life dose in MS patients is 140 mg/m2. Mitoxantrone is currently used as a second line drug in MS patients whose disease is not controlled by beta-interferon or glatiramer acetate. In this review, we will discuss the clinical disease patterns of MS patients who are most likely to benefit from mitoxantrone, its magnitude of clinical effect, and limitations of using mitoxantrone in MS. Mitoxantrone as a second line therapy in non-responders of beta-interferon and glatiramer acetate will be assessed. Recent strategies of combination therapy, and the optimal dose regimen will also be discussed.

Cytokines↗

PubMed2004

Blood T-cell receptor beta chain transcriptome in multiple sclerosis. Characterization of the T cells with altered CDR3 length distribution.

Multiple sclerosis is an inflammatory demyelinating disease of the CNS associated with T cells autoreactive for myelin components. In this study, we analysed the T-cell receptor (TCR) usage of the variable beta (Vbeta) chain transcriptome in the blood of multiple sclerosis patients at various stages of the disease using a global and quantitative comparison of the complementarity-determining region 3 length distribution (CDR3-LD) of transcripts of the 26 Vbeta genes. We investigated 35 patients: 12 with a high risk of multiple sclerosis, 10 with clinically definite multiple sclerosis, 13 with a relapsing-remitting worsening and active multiple sclerosis and 13 healthy individuals. Cells bearing the TCR transcripts with altered CDR3-LD were sorted and studied for CD4 or CD8 phenotype, cytokine transcript accumulation and response to human myelin basic protein (MBP). We show that patients from all the groups have a significantly skewed blood T-cell repertoire. Vbeta transcriptome patterns were more altered in patients from the clinically definite multiple sclerosis group and the worsening and active multiple sclerosis group than in the high risk group. The T cells sorted from Vbeta families with altered CDR3-LD concerned both CD4 and CD8 T cells, with a more pronounced skewing in the CD8 compartment. These cells displayed a significantly increased level of interferon-gamma, interleukin-2 and tumour necrosis factor-alpha transcripts compared with their counterparts from the healthy individual group. Furthermore, using interferon-gamma enzyme-linked immunospot (ELISPOT) assays, T cells from four out of seven altered Vbeta families tested from multiple sclerosis patients responded to human MBP, whereas no response was observed with human albumin or with altered Vbeta families from healthy individuals. Our data support the concept of an early autoimmune component in the disease and emphasize the possible involvement of CD8-positive T cells in multiple sclerosis.

Adult↗

PubMed2004

[Aggressive multiple sclerosis. Definition and specific therapeutic indication].

Introduction. On the 29th of October 2003, mitoxantrone was approved by the french health agency Afssaps (Agence française de sécurité sanitaire des produits de santé) for its use in the aggressive forms of multiple sclerosis (MS). It is the first immuno-suppressor having demonstrated particular efficacy in this progressive form of MS. Definition of aggressive MS. Agressive multiple sclerosis is defined as an MS that leads to the rapid accumumation of disabilities, whether these latter are the result of repeated relapses (at least 2 in the past 12 Months) or the continuous progression of a disability (increase in 2 points on the expanded disability status scale (EDSS) in the past 12 Months). The benefits of mitoxantrone. In cases of aggressive multiple sclerosis, mitoxantrone (20 mg IV), administered in Monthly cycles for 6 Months, clearly reduces the frequency of relapses, the appearance of new lesions on MRI and the progression of the disability. Precautions to be taken when using mitoxanthrone. The side effects however justify the fact that this drug is limited to the aggressive forms of MP. Cardiac toxicity limits the duration of the prescription and the maximum dose administered, requiring strict echocardiographical monitoring. Its unpredictable haematological toxicity can be devastating (risk of subsequent leukaemia). The benefit-risk ratio must be discussed with the patient and a Yearly echochardiography and three Monthly blood count must be continued during the 5 Years following withdrawal of mitoxantrone. The prescription of mitoxantrone is limited to the neurologists of departments specialized in neurology.

Adjuvants, Immunologic↗

PubMed2003

Investigation of seven proposed regions of linkage in multiple sclerosis: an American and French collaborative study.

Multiple sclerosis (MS) is a demyelinating autoimmune disease with a strong yet complex genetic component. To date only the HLA-DR locus, and specifically the HLA-DR15 allele, has been identified and confirmed as influencing the risk of developing MS. Genomic screens on several datasets have been performed and have identified several chromosomal regions with interesting results, but none have yet been confirmed. We tested seven of the most-promising regions (on chromosomes 1p, 2p, 3p, 3q, 5q, 19q, and Xp) identified from several genomic screens in a dataset of 98 multiplex MS families from the United States and 90 multiplex MS families from France. The results did not confirm linkage to 2p, 3q, 5q, or Xp in the overall dataset, or in subsets defined by geographic origin or HLA-DR15 status. Regions on 1p34, 3p14, and 19q13 produced lod scores >0.90 in at least one subset of the data, suggesting that these regions should be examined in more detail.

Chromosomes, Human, Pair 1↗

PubMed2003

Validation of diagnostic magnetic resonance imaging criteria for multiple sclerosis and response to interferon beta1a.

In the recently proposed diagnostic criteria for multiple sclerosis (MS) by McDonald, the modified magnetic resonance imaging (MRI) Barkhof criteria have been incorporated. We examined the validity of this implementation in the Early Treatment of MS study, a randomized, double-blind, placebo-controlled study of 22 microg interferon beta1a given subcutaneously once weekly in 309 patients with a first episode consistent with demyelinating disease (and abnormal MRI). Conversion to clinically definite MS (CDMS) within 2 years of follow-up, as evidenced by a new clinical episode, occurred in 41% of patients (independent of treatment) with gadolinium enhancement or nine or more T2 lesions versus 11% of those without either finding (p = 0.017); similarly, proportions converting were 44% versus 31% for infratentorial lesions (p = 0.026), 40% versus 35% for juxtacortical lesions (p = 0.413), and 41% versus 17% for three or more periventricular lesions (p = 0.034). The rate of conversion to CDMS based on the number of modified Barkhof criteria was 22% for two or fewer positive criteria, increasing to 47% with four positive criteria. For a cutoff of three positive criteria, the hazard ratio for time to CDMS was 2.3 (95% confidence interval, 1.17-4.55; p = 0.016). Treatment effect seemed more evident as the number of positive criteria increased, and the number of patients needed to avoid one patient converting to CDMS decreased from 50 in patients with one or two positive criteria to 5.6 in patients with four positive criteria. However, the study was not powered to detect statistically significant treatment by variable interaction, and this remains an important issue for further study.

Adjuvants, Immunologic↗

PubMed2003

Genetic interaction of CTLA-4 with HLA-DR15 in multiple sclerosis patients.

Multiple sclerosis is a chronic inflammatory disease of the central nervous system with a genetic component. Until now, the more consistent association with the disease is found with the major histocompatibility complex, especially HLA-DRB1*1501-DQB1*0602 haplotype. In this report, we demonstrate the interaction of Cytotoxic T Lymphocyte-associated antigen 4 (CTLA-4 [CD152]) gene with DRB1*15 haplotype in multiple sclerosis genetic susceptibility. Our data were obtained from two European independent family-based studies including 610 multiple sclerosis family trios. Ann Neurol 2003;54:119-122

Abatacept↗

PubMed2003

Genetic analysis of multiple sclerosis in Europeans: French data.

We report the results of a genome-wide screen for linkage disequilibrium (LD) in multiple sclerosis (MS) performed on 200 cases, 200 controls and 200 case-parent trios from France employing pooled DNA methodology. A total of 3510 microsatellite markers supplied through the GAMES collaborative were analysed and ranked according to their evidence for association. The most promising 117 markers were then followed up in a two-step validation process. In the first step, additional PCR of the DNA pools was performed in order to refine the ranking order. In the second step, markers were genotyped in individual cases and parents from the trio families. Seven markers showing nominally significant allele frequency differences between affected and unaffected emerged-D6S265, D12S1064, TNFa, D7S1824, D14S1426, D14S605 and D21S2051. These potential associations will require confirmation in further studies.

Alleles↗

PubMed2003

The effect of mitoxantrone on anti-pig immunization in baboons.

Besides virological and physiological concerns, the success of xenotransplantation (Xt) is still dependent on the prevention of delayed xenograft rejection (DXR). Although multifactorial, DXR is mainly due to xenonatural antibody (Ab) recognizing their xenogenic antigen (Ag) followed by complement activation. Despite the use of intensive treatments capable of inhibiting the humoral response, DXR can still not be avoided and always occurs within weeks following transplantation. Moreover, these latter treatments currently used in Xt could not be used clinically in humans because of their high risk of over-immunosuppressing the patients. Mitoxantrone (Mx) is a drug well known for its antiproliferative properties and is used clinically in oncology and in the treatment of relapsing multiple sclerosis. In models of arthritis in rats, it has been shown to be 10 to 20 times more powerful than cyclophosphamide (CyP) at blocking both inflammatory and B-cell responses. Because of its B-cell inhibitory capacity and considering the implication of the humoral response in xenograft rejection, we have compared Mx with CyP for its ability to block in vivo anti-pig immunization induced via subcutaneous injections of pig red blood cells into baboons. Neither drug was able to inhibit the anti-pig responses following the first and second immunizations, emphasizing the particularity of preformed Ab responses. However, the rise in Ab in the Mx treated animals was significantly delayed as compared with the non-treated as well as the CyP treated animals and was mainly because of a profound depletion of circulating B-cells. Mx displays an interesting antihumoral effect that we now intend to test in a pig kidney to baboon Xt model, with anticipated administration of the drug allowing an early B-cell depletion.

Animals↗

PubMed2002

Choreic syndrome due to Hashimoto's encephalopathy.

We report on the instructive case of an elderly woman who became encephalopathic and concurrently developed chorea. Thyroid antibody studies were abnormal. She responded extremely well to oral corticosteroids.

Aged↗