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Alemtuzumab: A Place in Therapy for Treatment of Multiple Sclerosis  [PDF]
Teya M. Tietje, Douglas R. Allington, Michael P. Rivey
International Journal of Clinical Medicine (IJCM) , 2013, DOI: 10.4236/ijcm.2013.410082
Abstract: Alemtuzumab is a humanized mononclonal antibody known to cause rapid depletion of B-and T-cell lymphocytes. Subsequent repletion of these lymphocytes leads to changes in adaptive immunity. Alemtuzumab is approved by the United States Food and Drug Administration (FDA) for the treatment of B-cell lymphocytic leukemia but has been investigated off-label in recent years for treatment of autoimmune diseases, including multiple sclerosis (MS). In MS treatment, alemtuzumab is administered as pulsed therapy, given once daily initially for 5 consecutive days and then for 3 consecutive days at 12-month intervals. Alemtuzumab has recently been compared to interferon beta 1-a in one phase II and two phase III trials in patients with relapsing-remitting MS. Results from the studies show alemtuzumab compared to interferon beta 1-a is associated with a greater reduction in the risk of sustained accumulation of disability and is more effective in reducing disease relapse rates. The treatment of MS continues to be a healthcare challenge due to the modest clinical benefit and adverse effect profiles of available disease modifying treatment options. Available data suggest alemtuzumab may offer better efficacy outcomes compared to traditional disease modifying therapies in patients with MS. However, the agent has not been compared to other new disease modifying medications that have been recently introduced.
Effect of GCSB-5, a Herbal Formulation, on Monosodium Iodoacetate-Induced Osteoarthritis in Rats
Joon-Ki Kim,Sang-Won Park,Jung-Woo Kang,Yu-Jin Kim,Sung Youl Lee,Joonshik Shin,Sangho Lee,Sun-Mee Lee
Evidence-Based Complementary and Alternative Medicine , 2012, DOI: 10.1155/2012/730907
Abstract: Therapeutic effects of GCSB-5 on osteoarthritis were measured by the amount of glycosaminoglycan in rabbit articular cartilage explants in vitro, in experimental osteoarthritis induced by intra-articular injection of monoiodoacetate in rats in vivo. GCSB-5 was orally administered for 28 days. In vitro, GCSB-5 inhibited proteoglycan degradation. GCSB-5 significantly suppressed the histological changes in monoiodoacetate-induced osteoarthritis. Matrix metalloproteinase (MMP) activity, as well as, the levels of serum tumor necrosis factor-α, cyclooxygenase-2, inducible nitric oxide synthase protein, and mRNA expressions were attenuated by GCSB-5, whereas the level of interleukin-10 was potentiated. By GCSB-5, the level of nuclear factor-κB p65 protein expression was significantly attenuated but, on the other hand, the level of inhibitor of κB-α protein expression was increased. These results indicate that GCSB-5 is a potential therapeutic agent for the protection of articular cartilage against progression of osteoarthritis through inhibition of MMPs activity, inflammatory mediators, and NF-κB activation.
Bo Fibiger - Nekrolog
J?rgen Bang
L?ring og Medier , 2010,
Abstract: Bo Fibiger 1945 - 2008
Fatigue in Multiple Sclerosis: (An update)  [cached]
Hossein Zarei
Journal of Research in Medical Sciences , 2007,
Abstract: BACKGROUND:To study the dimensions of fatigue in multiple sclerosis, its pathophysiology, the efficacy, tolerability and safety of drug and non-drug treatments and measurement of fatigue. METHODS: Relevant articles from PubMed and Google scholar search engines from January 1987 until September 2006 were studied to compose a short clinical update (not a systematic review) and make the required clinical information available for the clinicians. RESULTS: There is evidence that fatigue is very common in all types and stages of multiple sclerosis, but its pathophysiology is not well explained. Consequently, few drug options have been offered for its treatment. Amantadine is the bestknown drug, though its efficacy and duration of action are limited. Pemoline and modafinil are alternatives and have some effects on fatigue. DAP (diaminopyridine), ASA (acetylsalicylic acid), methylphenidate and fluoxetine are other possible options but await further confirmation. Neurorehabilitation, regular exercise and cooling are confirmed to be of value in MS treatment. Measurement of fatigue is a complicated issue. At present fatigue does not have a laboratory marker. CONCLUSIONS: The results of this short clinical update provide guidelines for diagnosing MS-related fatigue and differentiating it from other similar physical and psychological conditions. It also examines prescription drug options and other therapies for MS patients with fatigue. KEYWORDS: Multiple sclerosis, fatigue, pathophysiology, treatment, measurement.
Getting the Balance Right: A randomised controlled trial of physiotherapy and Exercise Interventions for ambulatory people with multiple sclerosis
Susan Coote, Maria Garrett, Neasa Hogan, Aidan Larkin, Jean Saunders
BMC Neurology , 2009, DOI: 10.1186/1471-2377-9-34
Abstract: This is a multi-centre, single blind, block randomised, controlled trial. Participants will be recruited via the ten regional offices of MS Ireland. Telephone screening will establish eligibility and stratification according to the mobility section of the Guys Neurological Disability Scale. Once a block of people of the same strand in the same geographical region have given consent, participants will be randomised. Strand A will concern individuals with MS who walk independently or use one stick to walk outside. Participants will be randomised to yoga, physiotherapy led exercise class, fitness instructor led exercise class or to a control group who don't change their exercise habits.Strand B will concern individuals with MS who walk with bilateral support or a rollator, they may use a wheelchair for longer distance outdoors. Participants will be randomised to 1:1 Physiotherapist led intervention, group intervention led by Physiotherapist, group yoga intervention or a control group who don't change their exercise habits. Participants will be assessed by physiotherapist who is blind to the group allocation at week 1, week 12 (following 10 weeks intervention or control), and at 12 week follow up. The primary outcome measure for both strands is the Multiple Sclerosis Impact Scale. Secondary outcomes are Modified Fatigue Impact Scale, 6 Minute Walk test, and muscle strength measured with hand held dynamometry. Strand B will also use Berg Balance Test and the Modified Ashworth Scale. Confounding variables such as sensation, coordination, proprioception, range of motion and other impairments will be recorded at initial assessment.Data analysis will analyse change in each group, and the differences between groups. Sub group analysis may be performed if sufficient numbers are recruited.ISRCTN77610415Multiple sclerosis (MS) is a demyelinating, degenerative disease of the central nervous system. It can cause a multitude of motor, sensory, visual, psychological, sexual, and bla
Impact of Fatigue and Disability on Quality of Life in Multiple Sclerosis
Soyuer, F.,Mirza, M.,?ztürk, A.
Erciyes Medical Journal , 2005,
Abstract: Purpose: To investigate the impact of fatigue and disability on the quality of life in 70 multiple sclerosis (MS) patients. Material and Methods: Quality of Life was assessed using the Functional Assessment of MS (FAMS). Disability was assessed using the Kurtzke’s expanded disability status scale (EDSS) and fatigue was quantified using the fatigue severity scale (FSS). Results: Fatigue groups (MSF) had more impaired scores than nonfatigue groups (MSNF) (p<0,05). Fatigue and disability were significantly associated with FAMS total and subgroups (p<0,05). Conclusion: Fatigue and disability have an effect on the quality of life.
Fatigue and Related Factors in Patients With Multiple Sclerosis  [PDF]
Taciser KAYA,Altinay Goksel KARATEPE,Aylin DEMIRHAN,Rezzan GUNAYDIN
Journal of Neurological Sciences , 2009,
Abstract: Objective: It was aimed in this study to determine the frequency and severity of fatigue and to investigate its relation to depression, disability level, and cognitive status in patients with multiple sclerosis.Patients and Methods: Seventy-nine multiple sclerosis patients, attending the outpatient multiple sclerosis clinic in our hospital, were recruited. The fatigue severity, disability level, cognitive status and depression were evaluated by using “Fatigue Severity Scale (FSS), Expanded Disability Status Scale (EDSS), Mini Mental Status Examination (MMSE) and Beck Depression Inventory (BDI) respectively. The relation between fatigue and the other parameters was measured by Spearman rank correlation analysis. To determine the most powerfull determinant of fatigue, multipl regression analysis was used.Results: The mean age of patients was 40.6±10.3 year, and the mean disease duration was 5 (1-32) [median (range)] year. It was determined that fatigue was present in 50.7% (N=40) of patients. When comparing fatigued (N=40) and nonfatigued (N=29) patients, EDSS and BDI scores were higher and duration of education and MMSE scores were lower in patients with fatigue (p<0.05). The severity of fatigue was significantly correlated to cognitive status and depression score (r= -0.301, p= 0.034; r= 0.419, p= 0.002 respectively). Regression analysis revealed that, the most powerfull determinant of fatigue is depression (r2= 0.179, p=0.002).Conclusion: In patients with multiple sclerosis, fatigue shouldn't be perceived as an physical outcome related only to disability level. Our data show that, fatigue should be interpreted as a symptom associated with depression in the course of rehabilitation of patients with multiple sclerosis.
Efficacy of Vitamin D Supplementation in Multiple Sclerosis (EVIDIMS Trial): study protocol for a randomized controlled trial
Jan D?rr, Stephanie Ohlraun, Horst Skarabis, Friedemann Paul
Trials , 2012, DOI: 10.1186/1745-6215-13-15
Abstract: The EVIDIMS trial is a German multi-center, stratified, randomized, controlled and double-blind clinical phase II pilot study. Eighty patients with the diagnosis of definite multiple sclerosis or clinically isolated syndrome who are on a stable immunomodulatory treatment with interferon-β1b will be randomized to additionally receive either high-dose (average daily dose 10.200 IU) or low-dose (average daily dose 200 IU) cholecalciferol for a total period of 18 months. The primary outcome measure is the number of new lesions detected on T2-weighted cranial MRI at 3 tesla. Secondary endpoints include additional magnetic resonance imaging and optical coherence tomography parameters for neuroinflammation and -degeneration, clinical parameters for disease activity, as well as cognition, fatigue, depression, and quality of life. Safety and tolerability of high-dose vitamin D supplementation are further outcome parameters.In light of the discrepancy between existing epidemiological and preclinical data on the one hand and available clinical data on the other the EVIDIMS trial will substantially contribute to the evaluation of the efficacy of high-dose vitamin D supplementation in MS patients. The study design presented here fulfills the criteria of a high-quality clinical phase II trial in MS.ClinicalTrials.gov Identifier: NCT01440062Multiple sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system (CNS) in western countries [1]. Based on autoimmune mediated damage to both glial and neuroaxonal structures, the disease is not yet curable and therapeutic options mainly focus on the control of the autoimmune reaction. The approved therapies include immunomodulatory (interferon-β, glatiramer acetate), (selective) immunosuppressive (fingolimod, azathioprine, mitoxantrone) or antibody-mediated (natalizumab) approaches. Additionally, new drugs are currently under investigation at different clinical stages. Although efficacy of all these drugs ha
On the motivic commutative ring spectrum BO  [PDF]
Ivan Panin,Charles Walter
Mathematics , 2010,
Abstract: We construct an algebraic commutative ring T- spectrum BO which is stably fibrant and (8,4)- periodic and such that on SmOp/S the cohomology theory (X,U) -> BO^{p,q}(X_{+}/U_{+}) and Schlichting's hermitian K-theory functor (X,U) -> KO^{[q]}_{2q-p}(X,U) are canonically isomorphic. We use the motivic weak equivalence Z x HGr -> KSp relating the infinite quaternionic Grassmannian to symplectic $K$-theory to equip BO with the structure of a commutative monoid in the motivic stable homotopy category. When the base scheme is Spec Z[1/2], this monoid structure and the induced ring structure on the cohomology theory BO^{*,*} are the unique structures compatible with the products KO^{[2m]}_{0}(X) x KO^{[2n]}_{0}(Y) -> KO^{[2m+2n]}_{0}(X x Y). on Grothendieck-Witt groups induced by the tensor product of symmetric chain complexes. The cohomology theory is bigraded commutative with the switch map acting on BO^{*,*}(T^{2}) in the same way as multiplication by the Grothendieck-Witt class of the symmetric bilinear space <-1>.
Survey validity of translation for Persian and cultural adaptation of Fatigue Impact Scale (FIS) questionnaire in multiple sclerosis patients in Iran
Marzieh Heidari,Melahat Akbarfahimi,Masoud Salehi,Seyed Masoud Nabavi
Modern Rehabilitation , 2012,
Abstract: Background and Aim: Fatigue is one of the most common problem of multiple sclerosis. It is a sign of inefficiency in the physical, social, and cognitive function. It is a major factor in limiting the responsibilities of social work of patients.The aim of this study was to translate and culturally adapt the Fatigue Impact Scale (FIS) in Iranian and create an appropriate tool for measuring the impact of fatigue and effectiveness of treatment and also rehabilitation interventions on fatigue in Iranian patients. Materials and Methods: In order to use the FIS in Iranian patients, the forward and backward translation and assessing the patient's perspective was done and the Persian version of the questionnaire was prepared. Results: The questionnaire was completed by twenty patients with multiple sclerosis. The time duration of filling out of each questionnaire took ten to twenty minutes .The final corrections was carried out. All questions of patients was acceptable and understandable and questions of "sexual activity" was completed only by married patients. The question of "financial support" was completed only by employed person (working people). Finally, as much as possible, this questionnaire was adapted with Iranian culture and sentences were confirmed by MAPI Institute. Conclusion: Persian version of the FIS is an appropriate tool for measuring the impact of fatigue, effectiveness of treatment and rehabilitation interventions on fatigue in patients with multiple sclerosis. Key words: Multiple sclerosis, fatigue, Fatigue Impact Scale, Forward translation and backward translation, Cultural adaptation
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