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https://www.readbyqxmd.com/read/28917696/brain-mapping-in-multiple-sclerosis-lessons-learned-about-the-human-brain
#1
REVIEW
Massimo Filippi, Paolo Preziosa, Maria A Rocca
The application of structural and functional magnetic resonance imaging (MRI) techniques in patients with multiple sclerosis (MS) has certainly helped to improve our understanding of the mechanisms responsible for clinical disability and cognitive impairment in this condition. The numerous studies performed in MS patients have also provided many lessons on the structure-function relationships in the human brain, which could be applied to healthy subjects and to patients affected by other neurological conditions...
September 13, 2017: NeuroImage
https://www.readbyqxmd.com/read/28915963/hepcidin-and-metallothioneins-as-molecular-base-for-sex-dependent-differences-in-clinical-course-of-experimental-autoimmune-encephalomyelitis-in-chronic-iron-overload
#2
Božena Ćurko-Cofek, Tanja Grubić Kezele, Vesna Barac-Latas
Multiple sclerosis is a chronic demyelinating disease of the central nervous system characterised by inflammatory and degenerative changes. It is considered that disease arises from the influence of environmental factors on genetically susceptible individuals. Recent researches, using magnetic resonance imaging, connected iron deposits in different brain regions with demyelinating process in multiple sclerosis patients. Although iron is an essential trace element important for many biological functions it could be harmful because iron excess can induce the production of reactive oxygen species, development of oxidative stress and lipid peroxidation which leads to demyelination...
September 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28914734/revisiting-the-concept-of-amyotrophic-lateral-sclerosis-as-a-multisystems-disorder-of-limited-phenotypic-expression
#3
Michael J Strong
PURPOSE OF REVIEW: The current review will examine the contemporary evidence that amyotrophic lateral sclerosis (ALS) is a syndrome in which the unifying feature is a progressive loss of upper and lower motor neuron function. RECENT FINDINGS: Although ALS is traditionally viewed as a neurodegenerative disorder affecting the motor neurons, there is considerable phenotypic heterogeneity and widespread involvement of the central nervous system. A broad range of both causative and disease modifying genetic variants are associated with both sporadic and familial forms of ALS...
September 13, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28913765/treatment-of-theiler-s-virus-induced-demyelinating-disease-with-teriflunomide
#4
Francesca Gilli, Libin Li, Darlene B Royce, Krista D DiSano, Andrew R Pachner
Teriflunomide is an oral therapy approved for the treatment of relapsing remitting multiple sclerosis (MS), showing both anti-inflammatory and antiviral properties. Currently, it is uncertain whether one or both of these properties may explain teriflunomide's beneficial effect in MS. Thus, to learn more about its mechanisms of action, we evaluated the effect of teriflunomide in the Theiler's encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) model, which is both a viral infection and an excellent model of the progressive disability of MS...
September 14, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28913726/diagnosis-and-treatment-of-progressive-multifocal-leukoencephalopathy-associated-with-multiple-sclerosis-therapies
#5
REVIEW
Eric M L Williamson, Joseph R Berger
Progressive multifocal leukoencephalopathy (PML) is a rare, but serious, complication encountered in patients treated with a select number of disease-modifying therapies (DMTs) utilized in treating multiple sclerosis (MS). PML results from a viral infection in the brain for which the only demonstrated effective therapy is restoring the perturbed immune system-typically achieved in the patient with MS by removing the offending therapeutic agent or, in the case of HIV-associated PML, treatment with highly active antiretroviral therapies...
September 14, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28912673/improving-the-delivery-of-sod1-antisense-oligonucleotides-to-motor-neurons-using-calcium-phosphate-lipid-nanoparticles
#6
Liyu Chen, Clare Watson, Marco Morsch, Nicholas J Cole, Roger S Chung, Darren N Saunders, Justin J Yerbury, Kara L Vine
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease affecting the upper and lower motor neurons in the motor cortex and spinal cord. Abnormal accumulation of mutant superoxide dismutase I (SOD1) in motor neurons is a pathological hallmark of some forms of the disease. We have shown that the orderly progression of the disease may be explained by misfolded SOD1 cell-to-cell propagation, which is reliant upon its active endogenous synthesis. Reducing the levels of SOD1 is therefore a promising therapeutic approach...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28906386/development-and-validation-of-a-prediction-score-system-in-lupus-nephritis
#7
Yi Tang, Wei Qin, Wei Peng, Ye Tao
The risk assessment for developing end-stage renal disease (ESRD) remains unclear in patients with lupus nephritis (LN). The purpose of this study was to develop and validate a prediction rule for estimating the individual risk of ESRD in patients with LN using clinical and pathological data.A total of 599 patients with LN diagnosed by renal biopsy between June 2009 and June 2014 in West China Hospital of Sichuan University were retrospectively followed. Patients were randomly divided into derivation cohort (n = 379) and validation cohort (n = 220)...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28899803/humanistic-and-cost-burden-of-systemic-sclerosis-a-review-of-the-literature
#8
REVIEW
Aryeh Fischer, Evelina Zimovetz, Caroline Ling, Dirk Esser, Nils Schoof
BACKGROUND: Systemic sclerosis (SSc), or systemic scleroderma, is a chronic multisystem autoimmune disease characterised by widespread vascular injury and progressive fibrosis of the skin and internal organs. Patients with SSc have decreased survival, with pulmonary involvement as the main cause of death. Current treatments for SSc manage a range of symptoms but not the cause of the disease. Our review describes the humanistic and cost burden of SSc. METHODS: A structured review of the literature was conducted, using predefined search strategies to search PubMed, Embase, and the Cochrane Library...
September 9, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28899203/an-overview-of-the-advantages-of-keap1-nrf2-system-activation-during-inflammatory-disease-treatment
#9
Nadine Keleku-Lukwete, Mikiko Suzuki, Masayuki Yamamoto
Inflammation can be defined as a protective immune response against harmful exogenous and endogenous stimuli. Nevertheless, prolonged or autoimmune inflammatory response are likely to cause pathological states associated with a production of inflammation-associated molecules along with ROS (reactive oxygen species). KEAP1-NRF2 (Kelch-like ECH-associated protein 1-Nuclear factor erythroid 2-related factor 2) signaling provides a cell protection mechanism against oxidative insults when endogenous stress defense mechanisms are imbalanced...
September 13, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28895473/neuroinflammation-in-amyotrophic-lateral-sclerosis-role-of-redox-dys-regulation
#10
Nadia D'Ambrosi, Mauro Cozzolino, Maria Teresa Carrì
SIGNIFICANCE: Amyotrophic lateral sclerosis (ALS) is due to degeneration of upper and lower motor neurons in the anterior horn of the spinal cord and in the motor cortex. Mechanisms leading to motor neuron death are complex and currently the disease is untreatable. Recent Advances. Work in genetic models of ALS indicates that an imbalance in the crosstalk that physiologically exists between motor neurons and the surrounding cells is eventually detrimental to motor neurons. In particular, the cascade of events collectively known as neuroinflammation and mainly characterized by a reactive phenotype of astrocytes and microglia, moderate infiltration of peripheral immune cells and elevated levels of inflammatory mediators has been consistently observed in motor regions of the central nervous system in sporadic and familial ALS, constituting a hallmark of the disease...
September 12, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28894553/effect-of-alpha-lipoic-acid-on-asymmetric-dimethylarginine-and-disability-in-multiple-sclerosis-patients-a-randomized-clinical-trial
#11
Mohammad Khalili, Madjid Soltani, Shirin Amiri Moghadam, Parvin Dehghan, Amirreza Azimi, Omid Abbaszadeh
BACKGROUND: Multiple Sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system. Oxidative stress plays a major role in the onset and progression of MS. Asymmetric dimethylarginine (ADMA) formation is dependent on oxidative stress status. OBJECTIVE: We examined whether alpha-lipoic acid (ALA) as a potent antioxidant could improve the Expanded Disability Status Scale (EDSS) and decrease plasma level of ADMA in multiple sclerosis patients...
July 2017: Electronic Physician
https://www.readbyqxmd.com/read/28886177/inflammatory-and-non-inflammatory-monocytes-as-novel-prognostic-biomarkers-of-survival-in-sod1g93a-mouse-model-of-amyotrophic-lateral-sclerosis
#12
Samanta Gasco, Pilar Zaragoza, Alberto García-Redondo, Ana C Calvo, Rosario Osta
Amyotrophic Lateral Sclerosis (ALS) has lately become a suitable scenario to study the interplay between the hematopoietic system and disease progression. Recent studies in C9orf72 null mice have demonstrated that C9orf72 is necessary for the normal function of myeloid cells. In this study, we aimed to analyze in depth the connection between the hematopoietic system and secondary lymphoid (spleen) and non-lymphoid (liver and skeletal muscle) organs and tissues along the disease progression in the transgenic SOD1G93A mice...
2017: PloS One
https://www.readbyqxmd.com/read/28875861/therapeutic-monoclonal-antibodies-and-multiple-sclerosis-the-essentials
#13
Ioannis Heliopoulos, Athanasia Patousi
BACKGROUND: Monoclonal antibodies (mAbs) are now established as targeted therapies for malignancies, transplant rejection, autoimmune and infectious diseases. Two monoclonal antibodies are available for treatment and other antibodies are currently being tested in multiple sclerosis (MS) patients. OBJECTIVES: The purpose of the present review paper is to outline the antibody engineering technologies, the immunologic and pharmacologic concepts of mΑbs and the current status of treatment in MS with emphasis on clinical efficacy and safety...
September 6, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/28872464/cns-inflammation-and-neurodegeneration
#14
Tanuja Chitnis, Howard L Weiner
There is an increasing recognition that inflammation plays a critical role in neurodegenerative diseases of the CNS, including Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, and the prototypic neuroinflammatory disease multiple sclerosis (MS). Differential immune responses involving the adaptive versus the innate immune system are observed at various stages of neurodegenerative diseases, and may not only drive disease processes but could serve as therapeutic targets. Ongoing investigations into the specific inflammatory mechanisms that play roles in disease causation and progression have revealed lessons about inflammation-driven neurodegeneration that can be applied to other neurodegenerative diseases...
September 5, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28871238/overcoming-therapeutic-inertia-in-multiple-sclerosis-care-a-pilot-randomized-trial-applying-the-traffic-light-system-in-medical-education
#15
Gustavo Saposnik, Jorge Maurino, Angel P Sempere, Maria A Terzaghi, Christian C Ruff, Muhammad Mamdani, Philippe N Tobler, Xavier Montalban
BACKGROUND: Physicians often do not initiate or intensify treatments when clearly warranted, a phenomenon known as therapeutic inertia (TI). Limited information is available on educational interventions to ameliorate knowledge-to-action gaps in TI. OBJECTIVES: To evaluate the feasibility and efficacy of an educational intervention compared to usual care among practicing neurologists caring for patients with multiple sclerosis (MS). METHODS: We conducted a pilot double-blind, parallel-group, randomized clinical trial...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28870573/cxcl10-and-cxcl13-chemokines-in-patients-with-relapsing-remitting-and-primary-progressive-multiple-sclerosis
#16
Piotr Iwanowski, Jacek Losy, Lucyna Kramer, Marlena Wójcicka, Elżbieta Kaufman
OBJECTIVES: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system characterized by a variable clinical course. Different pathogenic mechanisms responsible for relapsing remitting (RRMS) and primary progressive multiple sclerosis (PPMS) are modulated by immunological process with important role of chemokine network. CXCL10 and CXCL13 chemokines act as chemoattractants and modulators of proinflammatory reactions promoting process of demyelination...
September 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28869416/autologous-stem-cell-transplantation-in-systemic-sclerosis-a-systematic-review
#17
REVIEW
Lauren Host, Mandana Nikpour, Alicia Calderone, Paul Cannell, Janet Roddy
OBJECTIVES: Haematopoetic autologous stem cell transplantation (ASCT) has emerged as a treatment option for patients with refractory, severe autoimmune disease. This is a systematic review of the current literature on ASCT in adult patients with systemic sclerosis (SSc). METHODS: Original articles published between 2005 and 2016 that evaluated the use of ASCT in patients with SSc were reviewed with respect to the primary outcomes of overall and transplant related mortality (TRM) rates, and secondary outcomes of changes in modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), progression/event free survival (P/EFS) and quality of life measures...
August 30, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28861204/clinical-outcome-of-lateral-wedge-osteotomy-of-the-radius-in-advanced-stages-of-kienb%C3%A3-ck-s-disease
#18
Young Ho Shin, Jihyeung Kim, Hyun Sik Gong, Seung Hwan Rhee, Min Joon Cho, Goo Hyun Baek
BACKGROUND: Radius osteotomies showed favorable clinical outcome in Kienböck's disease. However, few articles have been published on the long-term outcome of lateral wedge osteotomy of the radius in patients with advanced stage Kienböck's disease. METHODS: Eleven patients with Lichtman stage IIIB/IV Kienböck's disease (group A; mean follow-up period, 86.1 months; range, 48 to 163 months) and 14 patients with Lichtman stage IIIA Kienböck's disease (group B; mean follow-up period, 85...
September 2017: Clinics in Orthopedic Surgery
https://www.readbyqxmd.com/read/28861122/the-role-of-natalizumab-in-the-treatment-of-multiple-sclerosis-benefits-and-risks
#19
REVIEW
Barry A Singer
Natalizumab, a monoclonal antibody that blocks lymphocyte infiltration in the central nervous system, is a valuable tool in the treatment of relapsing forms of multiple sclerosis (MS). In a phase III clinical trial comparing natalizumab with placebo over 2 years, natalizumab reduced annualized relapse rate by 68%, 12-week confirmed disability progression by 42%, and reduced contrast-enhancing lesions by 92%. In post hoc analyses, natalizumab treatment was associated with 37% of patients achieving no evidence of disease activity (versus 7% on placebo) and 30% achieving sustained disability improvement (versus 19% on placebo)...
September 2017: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/28859262/increased-levels-of-inflammatory-proteins-typify-the-earliest-phase-of-systemic-sclerosis
#20
Marta Cossu, Lenny van Bon, Carlo Preti, Marzia Rossato, Lorenzo Beretta, Timothy R D J Radstake
OBJECTIVE: Definite systemic sclerosis patients lacking fibrotic features stratify in an intermediate severity stage between preclinical/early (EaSSc) and fibrotic subsets (limited and diffuse cutaneous [lcSSc, dcSSc]). We aimed to molecularly characterize non-fibrotic SSc and EaSSc on the basis of a broad panel of serum markers of inflammation and tissue damage to increase the knowledge of pathophysiologic mechanisms underlying SSc progression before development of fibrosis. METHODS: An 88-plex immunoassay was performed in sera from a discovery cohort composed of 21 EaSSc (LeRoy and Medsger criteria), 15 non-fibrotic SSc (2013 ACR/EULAR criteria without skin or lung fibrosis) and 11 HC...
August 31, 2017: Arthritis & Rheumatology
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